Aquaporins (AQPs) are proteins that selectively transport water across the cell membrane. Although AQPs play important roles in secretion in the lacrimal gland, the expression and localization of AQPs have not been clarified yet. In the current study, we investigated the expression pattern of AQP family members in the murine lacrimal gland during development. Lacrimal gland tissues were harvested from E13.5 and E17.5 murine embryos and from mice 8 weeks of age (adults). Corneal and conjunctival tissues from the latter served as controls. Total RNA was isolated and analyzed for the expression of AQP family members using qPCR. The localization of AQPs in the adult lacrimal gland in adult murine lacrimal glands was also analyzed. Expression of Aqp8 and Aqp9 mRNAs was detected in the adult lacrimal gland but not in the cornea, conjunctiva, or fetal lacrimal gland. AQP8 and AQP9 and α-SMA partially colocalized around the basal regions of the acinar unit. The levels of Aqp3 mRNAs and protein were much lower in the adult lacrimal gland but were readily detected in the adult cornea and conjunctiva. Our study suggests that AQP8 and AQP9 may serve as markers for adult murine lacrimal gland, ductal, and myoepithelial cells.

Acute kidney injury (AKI) is responsible for significant mortality among hospitalized patients that is especially troubling aged people. An effective self-made Chinese medicine formula, Xiaoyu Xiezhuo Drink (XXD), displayed therapeutic effects on AKI. However, the compositions and underlying mechanisms of XXD remain to be elucidated. In this study, we used the ultra-high-performance liquid chromatography method coupled with hybrid triple quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) to investigate the chemical components in XXD. Then, the absorbable components of XXD were identified based on the five principles and inputted into the SwissTargetPrediction and STITCH databases to identify the drug targets. AKI-related targets were collected from the GenCLiP 3, GeneCards, and DisGeNET databases. The crossover genes of XXD and AKI were identified for functional enrichment analysis. The protein-protein interaction (PPI) network of crossover genes was constructed, followed by the identification of hub genes. Subsequently, the effects and potential mechanisms of XXD on AKI predicted by the network pharmacology and bioinformatics analyses were experimentally validated in ischemia-reperfusion (I/R) injury-induced AKI aged mouse models. A total of 122 components in XXD were obtained; among them, 58 components were found that could be absorbed in the blood. There were 800 potential drug targets predicted from the 58 absorbable components in AKI which shared 36 crossover genes with AKI-related targets. The results of functional enrichment analysis indicated that crossover genes mostly associated with the response to oxidative stress and the HIF1 signaling pathway. In the PPI network analysis, 12 hub genes were identified, including ALB, IL-6, TNF, TP53, VEGFA, PTGS2, TLR4, NOS3, EGFR, PPARG, HIF1A, and HMOX1. In AKI aged mice, XXD prominently alleviated I/R injury-induced renal dysfunction, abnormal renal pathological changes, and cellular senescence, inflammation, and oxidative damage with a reduction in the expression level of the inflammatory mediator, α-SMA, collagen-1, F4/80, TP53, VEGFA, PTGS2, TLR4, NOS3, EGFR, PPARG, HIF1A, ICAM-1, TGF-β1, Smad3, and p-Smad3 and an increase of nephridial tissue p-H3, Ki67, HMOX1, MMP-9, and Smad7 levels. In summary, our findings suggest that XXD has renoprotective effects against AKI in aged mice via inhibiting the TGF-β1/Smad3 and HIF1 signaling pathways.

The peroxisome proliferator-activated receptor (PPAR) α/γ-adenosine 5'-monophosphate- (AMP-) activated protein kinase- (AMPK-) sirtuin-1 (SIRT1) pathway and fatty acid metabolism are reported to be involved in influenza A virus (IAV) replication and IAV-pneumonia. Through a cell-based peroxisome proliferator responsive element- (PPRE-) driven luciferase bioassay, we have investigated 145 examples of traditional Chinese medicines (TCMs). Several TCMs, such as Polygonum cuspidatum, Rheum officinale Baillon, and Aloe vera var. Chinensis (Haw.) Berg., were found to possess high activity. We have further detected the anti-IAV activities of emodin (EMO) and its analogs, a group of common important compounds of these TCMs. The results showed that emodin and its several analogs possess excellent anti-IAV activities. The pharmacological tests showed that emodin significantly activated PPARα/γ and AMPK, decreased fatty acid biosynthesis, and increased intracellular ATP levels. Pharmaceutical inhibitors, siRNAs for PPARα/γ and AMPKα1, and exogenous palmitate impaired the inhibition of emodin. The in vivo test also showed that emodin significantly protected mice from IAV infection and pneumonia. Pharmacological inhibitors for PPARα/γ and AMPK signal and exogenous palmitate could partially counteract the effects of emodin in vivo. In conclusion, emodin and its analogs are a group of promising anti-IAV drug precursors, and the pharmacological mechanism of emodin is linked to its ability to regulate the PPARα/γ-AMPK pathway and fatty acid metabolism.

This study was aimed at fabricating and evaluating the physical and bioproperties of nanofast cement (NFC) as a replacement of the MTA. The cement particles were decreased in nanoscale, and zirconium oxide was used as a radiopacifier. The setting time and radiopacity were investigated according to ISO recommendations. Analysis of color, bioactivity, and cytotoxicity was performed using spectroscopy, simulated body fluid (SBF), and MTT assay. The setting time of cement pastes significantly dropped from 65 to 15 min when the particle sizes decreased from 2723 nm to 322 nm. Nanoparticles provide large surface areas and nucleation sites and thereby a higher hydration rate, so they reduced the setting time. Based on the resulting spectroscopy, the specimens did not exhibit clinically noticeable discoloration. Resistance to discoloration may be due to the resistance of zirconium oxide to decomposition. Scanning electron microscopy (SEM), X-ray diffraction (XRD), and infrared spectroscopy (FTIR) examinations of the immersed SBF samples showed apatite formation that was a reason for its suitable bioactivity. The results of cell culture revealed that NFC is nontoxic. This study showed that NFC was more beneficial than MTA in dental restorations.

Previous work stated that Khaya senegalensis, Anacardium ouest L., Pterocarpus erinaceus, Diospyros mespiliformis, Ocimum gratissimum, Manihot esculenta, Vernonia amygdalina Delile, and Daniellia oliveri have a great potential for the fight against infectious diarrhea. However, data on their antibacterial activity on strains of bacteria responsible for infectious diarrhea are not available. This study is aimed at elucidating the mechanism of action of the antibacterial effect of these plants on some bacterial strains responsible for diarrheal infections. The design of the study included first evaluating the degree of sensitivity of Salmonella typhimurium 14028, Escherichia coli ATCC 25922, Shigella spp., and Salmonella spp. strains to aqueous and hydroethanolic extracts of each plant, followed by the determination of minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and antibiotic power (Pa). This screening was completed with the evaluation of the possible mode of action of the extracts by testing the membrane permeability of these bacterial strains. The data collected indicate that the bacterial strains tested were sensitive to the extracts to varying degrees, except Cassia sieberiana DC and Pseudocedrela kotschyi extracts. For the active extracts, inhibition diameters ranged from 18.33 mm to 7 mm. With the exception of Escherichia coli, all strains were sensitive to the aqueous and hydroethanolic extracts of Anacardium occidentale. MICs vary between 3.37 and 25 mg/ml. Membrane permeability test data show that all active extracts affect the bacterial strains tested by attacking the stability of their outer membrane. For all active extracts, the high percentage of membrane destabilization of the bacteria is significantly (p < 0.05) better than that of cefixime used as a reference. Thus, it appears that these extracts can destroy Gram-negative bacteria and increase the fluidity and permeability of their cytoplasmic membrane. The knowledge of the mechanism of action of these extracts is an interesting contribution to the fundamental knowledge on the alternative that medicinal plants represent to antibiotics. These extracts can be used in the management of infectious diarrhea.

Ferroptosis and inflammation induced by cerebral hemorrhage result in an excessive inflammatory response and irreversible neuronal injury. Alleviating ferroptosis might be an effective way to prevent neuroinflammatory injury and promote neural functional recovery. Pyridoxal isonicotinoyl hydrazine (PIH), a lipophilic iron-chelating agent, has been reported to reduce excess iron-induced cytotoxicity. However, whether PIH could ameliorate the effects of hemorrhagic stroke is not completely understood. In the present study, the preventive effects of PIH in an intracerebral hemorrhage (ICH) mouse model were investigated. Neurological score, rotarod test, and immunofluorescence around the hematoma were assessed to evaluate the effects of PIH on hemorrhagic injury. The involvement of ferroptosis and inflammation was also examined in vitro to explore the underlying mechanism. Results showed that administration of PIH prevented neuronal cell death and reduced lipid peroxidation in Erastin-treated PC-12 cells. In vivo, mice treated with PIH after ICH attenuated neurological deficit scores. Additionally, we found PIH reduced ROS production, iron accumulation, and lipid peroxidation around the hematoma peripheral tissue. Meanwhile, ICH mice treated with PIH showed an upregulation of the key ferroptosis enzyme, glutathione peroxidase 4, and downregulation of cyclooxygenase-2. Moreover, PIH administration inhibited proinflammatory polarization and reduced interleukin-1 beta and tumor necrosis factor alpha in ICH mice. Collectively, these results demonstrated that PIH protects mice against hemorrhage stroke, which was associated with mitigation of inflammation and ferroptosis.

Medicinal plants are the chief components in the different oriental formulations in different traditional medical systems worldwide. As a thriving source of medicine, the medicinal plants with antituberculosis (TB) properties inspire the pharmacists to develop new drugs based on their active components or semimetabolites. In the present review, the anti-TB medicinal plants were screened from the scientific literatures, based on the botanical classification and the anti-TB activity. The obtained anti-TB medicinal plants were categorized into three different categories, viz., 159 plants critically examined with a total 335 isolated compounds, 131 plants with their crude extracts showing anti-TB activity, and 27 plants in literature with the prescribed formula by the traditional healers. Our systemic analysis on the medicinal plants can assist the discovery of novel and more efficacious anti-TB drugs.

The current scenario of the COVID-19 pandemic has forced dentists to seek different options for delivering healthcare services other than the in-person direct examination in clinical practice. Teledentistry is one of the options for remote patient care and monitoring. Objective. The present survey was conducted to assess the knowledge and perception of the dentists in Pakistan regarding teledentistry as an emergent supportive tool. Materials and Methods. A self-administered, close-ended, and prevalidated survey questionnaire was used, comprising 21 questions, and distributed electronically via e-mail, WhatsApp, and Facebook Messenger to evaluate the knowledge and perception of dentists regarding teledentistry. The data collected was compiled in a systematic manner and analyzed in terms of frequency (yes/no). Results. Out of a total of 350 dentists, 325 responded to the questionnaire, and it was seen that 62.5% of them did not have knowledge about teledentistry prior to COVID-19. 65.8% of dentists considered the practice of teledentistry in nonpandemic situations in the future. Conclusion. In the present study, it was observed that most of the dental professionals had inadequate knowledge about teledentistry before COVID-19, but the awareness and perception regarding teledentistry were currently satisfactory among the dental professionals in Pakistan. This emerging trend gives a positive hope for the implementation of teledentistry in the healthcare setup of Pakistan in the near future, as it will prove to be beneficial for safe dental practice during times of pandemic and even after.

Preoperative fasting causes significant perioperative discomfort in patients. Preoperative oral carbohydrate (POC) is an important element of the enhanced recovery after surgery protocol, but its effect on cirrhotic patients who tend to have abnormal gastric emptying remains unclarified. We investigated the influence of POC on gastric emptying and preprocedural well-being in cirrhotic patients. A prospective, randomized, controlled study of cirrhotic patients with gastroesophageal varices scheduled for elective therapeutic endoscopy under intravenous anesthesia was conducted. We enrolled 180 patients and divided them into three groups: those not supplemented with carbohydrates for 8 h before therapeutic endoscopy (control group) and those administered a carbohydrate beverage 2 h (2 h group) and 4 h (4 h group) before endoscopy. The residual gastric volume was quantified before anesthesia, gastric emptying was evaluated using gastric ultrasonography, and preprocedural well-being was assessed using the visual analogue scale (VAS). Preanesthesia gastric sonography scores were similar among the three groups. No patient had residual gastric volume > 1.5 ml/kg in the control and 4 h groups, but six patients (11%) had a residual gastric volume of >1.5 ml/kg in the 2 h group, hence were at a risk of regurgitation and aspiration. Moreover, VAS scores for six parameters (thirst, hunger, mouth dryness, nausea, vomiting, and fatigue) in the 2 h group and three parameters (thirst, hunger, and mouth dryness) in the 4 h group were significantly lower than those in the control group, suggesting a beneficial effect on cirrhotic patients' well-being. Preoperative gastric peristaltic and operation scores, postoperative complications, length of hospital stay, and in-hospital expenses were not significantly different among the three groups. Our study indicated that avoiding preoperative fasting with oral carbohydrates administered 4 h before anesthesia can be achieved in cirrhotic patients. Further studies to assess whether POC can help improve postoperative outcomes in cirrhotic patients are needed.

INTRODUCTION: Recent experiences from global outbreaks have highlighted the severe disruptions in sexual and reproductive health services that expose women and girls to preventable health risks. Yet, to date, there is no review studying the possible impact of outbreaks on sexual and reproductive health (SRH). Methodology. Studies reporting outbreaks impacting sexual and reproductive health and pregnancy outcomes were identified using MEDLINE, Embase, and ISI-WoS. Reported impacts were reviewed at systems, community, and legislative levels. RESULTS: The initial run listed 4423 studies; the 37 studies that met all inclusion criteria were mainly from Latin America and Africa. Studies on outbreaks of diseases like Zika and Ebola have documented declines in facility-based deliveries, contraceptive use, and antenatal and institutional care due to burdened healthcare system. Service usage was also impacted by a lack of trust in the healthcare system and system shocks, including workforce capacity and availability. At the community level, poverty and lack of awareness were critical contributors to poor access to SRH services. Assessing the target population's knowledge, attitude, beliefs, and behavior and using health literacy principles for communication were fundamental for designing service delivery. Online resources for SRH services were an acceptable medium of information among young adults. In outbreak situations, SRH and pregnancy outcomes were improved by implementing laboratory surveillance, free-of-cost contraceptive services, improved screening through professional training, and quality of care. In addition, mobile health clinics were reported to be effective in remote areas. Knowledge Contribution. In outbreaks, the interventions are categorized into preoutbreak, during, and postoutbreak periods. The proposed steps can help to improve and do course correction in emergencies. Though conducted before the COVID-19 crisis, the authors believe that lessons can be drawn from the paper to understand and mitigate the impact of the pandemic on sexual and reproductive health services.

BACKGROUND: Respiratory syncytial virus (RSV) infects infants and children, predisposing them to development of asthma during adulthood. Epithelial neuroendocrine phenotypes may be associated with development of asthma. This study hopes to ascertain if RSV infection promotes epithelial neuroendocrine phenotypes through the NODAL signaling pathway. METHODS: The GSE6802 data set was obtained from the GEO database, and the differential genes were analyzed using the R language. An in vitro model was constructed with RSV infected human respiratory epithelial cells, and then real-time qPCR and immunofluorescence were used to detect the expression of different epithelial biomarkers and airway neuropeptides. The acute and chronic infection model of RSV infection was established by intranasal injection of RSV into guinea pigs. Immunohistochemistry and Western blot were used to detect the expression of pulmonary neuroendocrine cells markers ENO2 and neuropeptides. RESULTS: The expression levels of ENO2, SP, CGRP, and NODAL/ACTRII were significantly higher in the RSV infection group than those of the control group, which were abrogated by siRNA-NODAL. In vivo, we found that the expression levels of ENO2, SP, and CGRP were significantly higher than that of the control group. CONCLUSION: RSV promotes epithelial neuroendocrine phenotypes through the NODAL signaling pathway.

BACKGROUND: The oral health care of autistic children is elaborated; they often fail to define dental problems, and a family-centered approach can be useful to improve and intercept these disorders. AIM: To assess the oral status of autistic children, comparing it with no autistic patients. MATERIALS AND METHODS: A retrospective study analyzed the oral health status of 70 children, 35 with autism and 35 without the disorder. Conditions assessed were dental trauma type, periodontal tissue injuries, soft tissue lip injuries, different treatments carried out, associated soft tissue findings and disorders, and the long-term management. All patients (≤15 years of age) were chosen consecutively. RESULTS: Females (57%) suffered more traumatic injuries than males (43%) in the autistic group, whereas males affected by dental trauma (54%) are predominant in the control group. The enamel fracture was the main finding among the dental trauma types in both groups followed by enamel/dentin/pulp fracture (31%), root fracture (11%), and avulsions (3%) in the autistic group and by avulsions (20%), root fracture (11%), and enamel/dentin/pulp fracture (6%) in the control group. The comparison of all variables of the two groups showed a statistically significant difference (P < 0.012). The lower lip was statistically more injured than the upper lip (P < 0.005). CONCLUSIONS: The composite restorative technique was the most common approach carried out; the long-term evaluation, when possible, was predominantly managed through root canal therapy in the control group (81%), and root canal therapy (50%) and tooth extraction (50%) in the sample group.

BACKGROUND: Psoriasis is a chronic autoimmune disease impairing significantly the quality of life of the patient. The diagnosis of the disease is done via a visual inspection of the lesional skin by dermatologists. Classification of psoriasis using gene expression is an important issue for the early and effective treatment of the disease. Therefore, gene expression data and selection of suitable gene signatures are effective sources of information. METHODS: We aimed to develop a hybrid classifier for the diagnosis of psoriasis based on two machine learning models of the genetic algorithm and support vector machine (SVM). The method also conducts gene signature selection. A publically available gene expression dataset was used to test the model. RESULTS: A number of 181 probe sets were selected among the original 54,675 probes using the hybrid model with a prediction accuracy of 100% over the test set. A number of 10 hub genes were identified using the protein-protein interaction network. Nine out of 10 identified genes were found in significant modules. CONCLUSIONS: The results showed that the genetic algorithm improved the SVM classifier performance significantly implying the ability of the proposed model in terms of detecting relevant gene expression signatures as the best features.

BACKGROUND: Previous studies have shown that heart failure (HF) and chronic kidney disease (CKD) have common genetic mechanisms, overlapping pathophysiological pathways, and therapeutic drug-sodium-glucose cotransporter 2 (SGLT2) inhibitors. METHODS: The genetic pleiotropy metaCCA method was applied on summary statistics data from two independent meta-analyses of GWAS comprising more than 1 million people to identify shared variants and pleiotropic effects between HF and CKD. Targets of SGLT2 inhibitors were predicted by SwissTargetPrediction and DrugBank databases. To refine all genes, we performed using versatile gene-based association study 2 (VEGAS2) and transcriptome-wide association studies (TWAS) for HF and CKD, respectively. Gene enrichment and KEGG pathway analyses were used to explore the potential functional significance of the identified genes and targets. RESULTS: After metaCCA analysis, 4,624 SNPs and 1,745 genes were identified to be potentially pleiotropic in the univariate and multivariate SNP-multivariate phenotype analyses, respectively. 21 common genes were detected in both metaCCA and SGLT2 inhibitors' target prediction. In addition, 169 putative pleiotropic genes were identified, which met the significance threshold both in metaCCA analysis and in the VEGAS2 or TWAS analysis for at least one disease. CONCLUSION: We identified novel variants associated with HF and CKD using effectively incorporating information from different GWAS datasets. Our analysis may provide new insights into HF and CKD therapeutic approaches based on the pleiotropic genes, common targets, and mechanisms by integrating the metaCCA method, TWAS and VEGAS2 analyses, and target prediction of SGLT2 inhibitors.

OBJECTIVE: Bevacizumab was currently available for nonsquamous non-small-cell lung cancer (NSqNSCLC) patients and has been studied in several randomized controlled trials (RCTs) for treatment of these patients. This meta-analysis summarizes the most up-to-date evidences regarding the effects and adverse reactions of bevacizumab in the treatment of NSqNSCLC patients. METHODS: The authors searched for RCTs from electronic database including PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. Experimental arm was defined as the bevacizumab-containing group and the control arm as the bevacizumab-free group. Data of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse reactions were synthetically extracted. A protocol for this meta-analysis has been registered on PROSPERO (http://www.crd.york.ac.uk/prospero). RESULTS: Ten RCTs that involved a total of 3134 patients were included. The experimental group was associated with significant superior ORR (RR 1.63, 95% CI 1.24 to 2.14, P < 0.001), OS (HR 0.90, 95% CI 0.82 to 0.99, P < 0.001), and prolonged PFS (HR 0.68, 95% CI 0.62 to 0.74, P < 0.001) compared to the control. No significant difference was observed regarding DCR (RR 1.13, 95% CI 0.99 to 1.30, P = 0.08). The experimental group showed higher rate of hypertension (RR 6.91, 95% CI 4.62 to 10.35, P < 0.00001) and hemorrhagic events (RR 3.07, 95% CI 1.78 to 5.30, P < 0.0001) than the control group. The experimental group showed lower rate of anemia (RR 0.72, 95% CI 0.55 to 0.96, P = 0.02) than the control group. No significant difference was observed regarding treatment-related adverse event grade 3-5 (TRAE3-5) (RR 1.23, 95% CI 0.99 to 1.53, P = 0.06), thrombocytopenia (RR 1.11, 95% CI 0.92 to 1.33, P = 0.29), and neutropenia (RR 1.11, 95% CI 0.88 to 1.40, P = 0.36). CONCLUSION: This meta-analysis showed that bevacizumab could increase ORR, OS, and prolonged PFS for treatment of NSqNSCLC patients. However, no significant improvement in DCR was observed and bevacizumab could increase the rate of hypertension and hemorrhagic events. Bevacizumab was an acceptable option for NSqNSCLC patients. This trial is registered with PROSPERO registration number: CRD42021226790.

Choroidal neovascularization (CNV) is a type of eye disease that can cause vision loss. In recent years, many studies have attempted to investigate the major pathological processes and molecular pathogenic mechanisms of CNV. Because many diseases are related to genes, the genes associated with CNV need to be identified. In this study, we proposed a network-based approach for identifying novel CNV-associated genes. To execute such method, we first employed a protein-protein interaction network reported in STRING. Then, we applied a network diffusion algorithm, Laplacian heat diffusion, on this network by selecting validated CNV-related genes as the seed nodes. As a result, some novel genes that had unknown but strong relationships with validated genes were identified. Furthermore, we used a screening procedure to extract the most essential genes. Eleven latent CNV-related genes were finally obtained. Extensive analyses were performed to confirm that these genes are novel CNV-related genes.

OBJECTIVE: Analyzing and comparing the fit and accuracy of removable partial denture (RPDs) frameworks fabricated with CAD/CAM and rapid prototyping methods with conventional techniques. MATERIALS AND METHODS: The present systematic review was carried out according to PRISMA guidelines. The search was carried out on PubMed/MEDLINE, Cochrane collaboration, Science direct, and Scopus scientific engines using selected MeSH keywords. The articles fulfilling the predefined selection criteria based on the fit and accuracy of removable partial denture (RPD) frameworks constructed from digital workflow (CAD/CAM; rapid prototyping) and conventional techniques were included. RESULTS: Nine full-text articles comprising 6 in vitro and 3 in vivo studies were included in this review. The digital RPDs were fabricated in all articles by CAD/CAM selective laser sintering and selective laser melting techniques. The articles that have used CAD/CAM and rapid prototyping technique demonstrated better fit and accuracy as compared to the RPDs fabricated through conventional techniques. The least gaps between the framework and cast (41.677 ± 15.546 μm) were found in RPDs constructed through digital CAD/CAM systems. CONCLUSION: A better accuracy was achieved using CAD/CAM and rapid prototyping techniques. The RPD frameworks fabricated by CAD/CAM and rapid prototyping techniques had clinically acceptable fit, superior precision, and better accuracy than conventionally fabricated RPD frameworks.

OBJECTIVE: Schizencephaly is a rare congenital malformation that causes motor impairment. To determine the treatment strategy, each domain of the motor functions should be appropriately evaluated. We correlated a color map of diffusion tensor imaging (DTI) and transcranial magnetic stimulation (TMS) with the hand function test (HFT) to identify the type of hand function that each test (DTI and TMS) reflects. Further, we attempted to demonstrate the motor neuron organization in schizencephaly. METHOD: This retrospective study was conducted on 12 patients with schizencephaly. TMS was conducted in the first dorsal interosseous (FDI), biceps (BB), and deltoid muscles of the upper extremity, and contralateral MEP (cMEP) and ipsilateral MEP (iMEP) were recorded. The HFT included the grip strength, box and block (B&B), and 9-hole peg test. The schizencephalic cleft was confirmed using magnetic resonance imaging, and the corticospinal tract (CST) was identified using the color map of DTI. The symmetry indices for the peduncle and CST at pons level were calculated as the ratios of the cross-sectional area of the less-affected side and that of the more-affected side. RESULT: In the more-affected hemisphere TMS, no iMEP was obtained. In the less-affected hemisphere TMS, the iMEP response was detected in 9 patients and cMEP in all patients, which was similar to the pattern observed in unilateral lesion. Paretic hand grip strength was strongly correlated with the presence of iMEP (p = 0.044). The symmetry index of the color map of DTI was significantly correlated with the B&B (p = 0.008, R 2 = 0.416), whereas the symmetry index of the peduncle was not correlated with all HFTs. CONCLUSION: In patients with schizencephaly, the iMEP response rate is correlated with the hand function related to strength, while the symmetricity of the CST by the color map of DTI is correlated with the hand function associated with dexterity. Additionally, we suggest the possible motor organization pattern of schizencephaly following interhemispheric competition.

To the best of our knowledge, there is no annotated database of PPG signals recorded by smartphone publicly available. This article introduces Brno University of Technology Smartphone PPG Database (BUT PPG) which is an original database created by the cardiology team at the Department of Biomedical Engineering, Brno University of Technology, for the purpose of evaluating photoplethysmographic (PPG) signal quality and estimation of heart rate (HR). The data comprises 48 10-second recordings of PPGs and associated electrocardiographic (ECG) signals used for determination of reference HR. The data were collected from 12 subjects (6 female, 6 male) aged between 21 and 61. PPG data were collected by smartphone Xiaomi Mi9 with sampling frequency of 30 Hz. Reference ECG signals were recorded using a mobile ECG recorder (Bittium Faros 360) with a sampling frequency of 1,000 Hz. Each PPG signal includes annotation of quality created manually by biomedical experts and reference HR. PPG signal quality is indicated binary: 1 indicates good quality for HR estimation, 0 indicates signals where HR cannot be detected reliably, and thus, these signals are unsuitable for further analysis. As the only available database containing PPG signals recorded by smartphone, BUT PPG is a unique tool for the development of smart, user-friendly, cheap, on-the-spot, self-home-monitoring of heart rate with the potential of widespread using.

BACKGROUND: About 1/3 of tibial plateau fractures are associated with proximal fibula fractures, but most proximal fibula fractures are often ignored. The aim of this study was to precisely explain the classification and treatment strategies of six injury types of the fibular column associated with tibial plateau fractures. METHODS: Patients with ipsilateral proximal fibula and tibial plateau fractures treated in our hospital were retrospectively reviewed from Aug 2007 to Mar 2020. Two experienced surgeons and two radiologists divided fibular column injury into 6 injury types according to the AO classification and four-column nine-segment classification. The treatment scheme (surgically treated or conservatively treated) was also recorded. RESULTS: In total, 355 proximal fibula fractures were included. Type 2 fibular head fracture was the most common type of injury in 122, and the segregate of superior tibiofibular syndesmosis was the rarest type in 3. In avulsion injury proximal of fibular pattern, the proportion of patients who need surgical intervention is the highest. CONCLUSIONS: Six injury types in the four-column nine-segment classification covered all types of bony and soft tissue injuries of the fibular column and concisely explained the injury mechanism. The classification is helpful for the precise judgement and decision-making of the concomitant fibular column injuries in tibial plateau fractures.

Endothelin is a chemical mediator that helps in maintaining balance within the blood-brain barrier by regulating the levels of toxicants and molecules which pass through the brain, suggesting that a rise in its production determines Alzheimer's disease. The inequity in the amyloid β occurs due to a problem in its clearance from the brain initiating the production of reactive oxygen species and superoxide that activates a cascade wherein the release of inflammatory mediators and various enzymes like endothelin-converting enzymes take place. Furthermore, the cascade increases the levels of endothelin in the brain from endothelial cells. Endothelin levels are upregulated, which can be regulated by modulating the action of endothelin-converting enzymes and endothelin receptors. Hence, endothelin paves a pathway in the treatment of Alzheimer's disease. In this article, we have covered various mechanisms and preclinical studies that support and direct endothelin involvement in the progression of Alzheimer's disease by using various search tools such as PubMed, Science Direct, and Medline. Conclusive outcome data were extracted that all together defy contrivance pathways, potential drugs, endothelin receptors, and endothelin enzymes in our article giving profound importance to target endothelin for prevention and treatment of Alzheimer's disease.

Under changing climate, water scarcity and frequent incidence of diseases like stripe rust pose the biggest threat to sustainable crop production which jeopardizes nutritional security. A study was executed to rationalize crop water requirement and evaluate wheat (Triticum aestivum L. cv. Bohoth 3) yield losses by stripe rust infection under irrigated conditions. Seven water treatments included three irrigations in three stages/season (S 3), four irrigations (S 4), and five irrigations (S 5) at the different sensitive growth stages, full (F), and two deficit irrigation levels including D 1 = 80% of field capacity (FC) and D 2 = 70% (FC) along with farmers' practice of irrigation as control (C). Results revealed that F and D 1 boosted grain yield by 31 and 14%. Overall, F irrigation regime resulted in the highest grain production (2.93 ton/ha) as well as biomass yield (13.2 ton/ha). However, D 2 had the highest value of grain protein (15.9%) and achieved the highest application efficiency (AE) at midseason (54.6%) and end season (59.6%), and the lowest AE was under S 3. Also, halting irrigation at the milky stage (S 5) led to a significant decrease in irrigation water use efficiency as compared to D 1. However, cutting irrigation at the end of seedling, heading, and milky stages (S 3) caused a significant reduction in E a, crop water use (ETa), and 1000 grain weight in comparison with all other treatments. Regarding yellow rust, S 3 irrigation regime resulted in the lowest incidence of yellow rust infection. The highest irrigation and water use efficiency values were recorded under D 1 (0.79 and 0.59 kg/m3), and the lowest values were obtained for control. Hence, the deficit irrigation treatment D 1 could be recommended as the best appropriate strategy to save more water and to improve the water productivity under Yemeni agroclimatic conditions.

Recent studies have supported the relationship between periodontitis and carotid artery calcification (CAC), but still uncertain. This systematic review is aimed at evaluating the association between periodontitis and CAC. The search was conducted in four electronic databases: PubMed, EMBASE, Web of Science, and The Cochrane Library, supplemented by checking references of included articles and related review articles. Eligibility assessment and data extraction were conducted independently. The quality assessment and publication bias analysis were performed. The association between periodontitis and CAC was presented in odd ratio (OR) with 95% confidence interval (CI). Additional outcomes included the percentage of alveolar bone loss in CAC versus non-CAC. Twelve studies were included, and 10 were performed quantity analysis. Periodontitis with secure definition (OR = 2.02, 95%CI = 1.18 - 3.45) and insecure definition (OR = 10.78, 95%CI = 4.41 - 26.34) was associated with CAC. And a higher average percentage of alveolar bone loss (weighted mean difference = 10.84%; 95%CI = 6.40 - 15.48) was also observed in CAC patients compared to non-CAC patients. No significant publication bias was found. The results of this systematic review and meta-analysis revealed a significant relationship between periodontitis and CAC.

Currently, the impact of electromagnetic field (EMF) exposure on the nervous system is an increasingly arousing public concern. The present study was designed to explore the effects of continuous long-term exposure to L-band high-power microwave (L-HPM) on brain function and related mechanisms. Forty-eight male Institute of Cancer Research (ICR) mice were exposed to L-HPM at various power densities (0.5, 1.0, and 1.5 W/m2) and the brain function was examined at different time periods after exposure. The morphology of the brain was examined by hematoxylin-eosin (HE) and deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. Furthermore, cholinergic markers, oxidative stress markers, and the expression of c-fos were evaluated to identify a "potential" mechanism. The results showed that exposure to L-HPM at 1.5 W/m2 can cause generalized injuries in the hippocampus (CA1 and CA3) and cerebral cortex (the first somatosensory cortex) of mice, including cell apoptosis, cholinergic dysfunction, and oxidative damage. Moreover, the deleterious effects were closely related to the power density and exposure time, indicating that long-term and high-power density exposure may be detrimental to the nervous system.

The global burden of viral infection, especially the current pandemics of SARS-CoV-2, HIV/AIDS, and hepatitis, is a very risky one. Additionally, HCV expresses the necessity for antiviral therapeutic elements. Venoms are known to contain an array of bioactive peptides that are commonly used in the treatment of various medical issues. Several peptides isolated from scorpion venom have recently been proven to possess an antiviral activity against several viral families. The aim of this review is to provide an up-to-date overview of scorpion antiviral peptides and to discuss their modes of action and potential biomedical application against different viruses.

BACKGROUND: The aim of the present study is to compare the dental anxiety levels between two outpatient clinics. METHODS: Two hundred and seventy patients treated in two different clinics of minor oral surgery and dental extraction polyclinic in the Dental Faculty of Eskisehir Osmangazi University were included in the study. The impacted third molar surgery group and conventional dental extraction group consisted of 101 and 169 patients, respectively. The Modified Dental Anxiety Scale (MDAS) and Dental Fear Scale (DFS) were used to measure anxiety levels in patients treated in both clinics. Tests were made in an isolated room preoperatively. The differences in anxiety levels according to education status and gender were also evaluated. RESULTS: The impacted third molar surgery group showed a significant increase in dental anxiety measured with DFS questionnaire (p < 0.05). However, MDAS revealed that there was no difference between anxiety levels between the impacted third molar surgery and conventional dental extraction groups (p > 0.05). There was also no difference in anxiety levels between patients with different education status (p > 0.05). Female patients demonstrated higher levels of anxiety in both MDAS and DFS indexes (p < 0.05). CONCLUSION: Dental anxiety may be higher in patients treated with impacted third molar surgery compared with conventional dental extraction. The education status of patients may not affect dental anxiety. Female patients may show increased levels of dental anxiety in conventional dental and impacted third molar extractions.

The object of this study was to prepare binary and ternary solid dispersions of atorvastatin (ATR) by the melting method using PEGs and poloxamer 188 (P188) as the carriers, singly and in combination with each other. Dissolution behavior, solubility studies, X-ray diffractometry, differential scanning calorimetry, and Fourier transform infrared spectroscopy were studied. Furthermore, antihyperlipidemic activities of formulations were compared to each other by serum lipid analyses in hyperlipidemic rats. Based on the results, the highest dissolution efficiency (DE30 = 83%) was obtained by binary systems consisted of ATR and P188. Also, no additional improvement was observed in dissolution properties of ternary solid dispersion formulations. Solubility studies showed enhancement of ATR phase solubility in water and a buffer solution containing P188 or PEG 10000. Furthermore, saturated solubility of ATR in the buffer solution improved more than twofold in the optimized ternary dispersion system. No crystalline changes occurred in PEG-based formulations; meanwhile, partial amorphization happened in the ATR-P188 combination. Finally, the in vivo study in hyperlipidemic rats exhibited a rapid decrease in the lipid profile of all formulations compared to ATR (after 7 days). Moreover, reduction of serum triglycerides and total cholesterol on the 14th day in the ATR group (p value < 0.01) was less than solid dispersion or physical mixing preparations (p value < 0.001). These findings proved the appropriate influence of using PEG and P188 in solid dispersion systems for the improvement of the therapeutic efficiency of ATR.

The existing paired t-test under classical statistics cannot be applied when the data is obtained from the complex process, having interval, uncertainty, indeterminacy, and incompleteness. In this paper, the modification of the paired t-test under neutrosophic statistics is proposed. The testing criterion of the proposed paired t-test is given. The application of the proposed paired t-test is given using the interval quality control of clinical laboratory data. From the analysis, it can be seen than the proposed test is quite effective and informative to apply for testing the measurement tools in the clinical laboratory.

Malaria is a life-threatening disease caused by Plasmodium and represents one of the main public health problems in the world. Among alterations associated with the disease, we highlight the hepatic impairment resulting from the generation of oxidative stress. Studies demonstrate that liver injuries caused by Plasmodium infection are associated with unbalance of the antioxidant system in hepatocytes, although little is known about the role of antioxidant molecules such as glutathione and vitamin C in the evolution of the disease and in the liver injury. To evaluate disease complications, murine models emerge as a valuable tool due to their similarities between the infectious species for human and mice. Herein, the aim of this study is to evaluate the effect of antioxidants glutathione and vitamin C on the evolution of murine malaria and in the liver damage caused by Plasmodium berghei ANKA infection. Mice were inoculated with parasitized erythrocytes and treated with glutathione and vitamin C, separately, both at 8 mg/kg during 7 consecutive days. Our data showed that during Plasmodium infection, treatment with glutathione promoted significant decrease in the survival of infected mice, accelerating the disease severity. However, treatment with vitamin C promoted an improvement in the clinical outcomes and prolonged the survival curve of infected animals. We also showed that glutathione promoted increase in the parasitemia rate of Plasmodium-infected animals, although treatment with vitamin C has induced significant decrease in parasitemia rates. Furthermore, histological analysis and enzyme biochemical measurement showed that treatment with glutathione exacerbates liver damage while treatment with vitamin C mitigates the hepatic injury induced by the infection. In summary, the current study provided evidences that antioxidant molecules could differently modulate the outcome of malaria disease; while glutathione aggravated the disease outcome and liver injury, the treatment with vitamin C protects the liver from damage and the evolution of the condition.

OBJECTIVE: Provide a reference to elucidate the mechanism of circRNAs regulating osteoarthritis (OA) and the clinical treatment. METHODS: Herein, articles about circRNAs (hsa-circ) and osteoarthritis in the recent 5 years have been reviewed and the differential expression and regulatory effect of circRNAs in OA deduced. Based on these conclusions and Protein-Protein Interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the acquired circRNAs, the potential functions and interactions of circRNAs in OA and the involved signaling pathways are discussed. RESULTS: A total of 33 studies meeting the inclusion criteria were included in this study, and 27 circRNAs were upregulated and 8 circRNAs were downregulated in OA. A total of 31 circRNAs were finally included in the PPI, GO, and KEGG analyses. From PPI, 12 map nodes and 7 map edges were interrelated. VWF had the biggest node and edge size. From GO, VWF showed a majority of the functions. From KEGG, circRNAs are enriched in PI3K/AKT, human papillomavirus infection (HPI), and focal adhesion (FA) pathways, and VWF was involved in major pathways. CONCLUSION: We found that most articles about circRNAs regulating OA in the recent 5 years focused on the mechanism, especially the absorption effect of circ-miRNA as sponges in the recent 2 years, while most of the articles about their functions addressed ECM and PI3K, AKT, and mTOR signaling pathways. Future studies might focus on the functions of circRNAs, and circRNA VWF, with preferable functions, interactions, and involvement, can be used as a biological indicator to detect OA in clinical practice.

The aim of the current study was to establish whether the vertebral morphometry (e.g., vertebral body width and spinal canal diameters) is associated with degenerative lumbar spinal stenosis (DLSS). A retrospective computerized tomography (CT) study from L1 to L5 for two sample populations was used. The first included 165 participants with symptomatic DLSS (sex ratio 80 M/85F), and the second had 180 individuals from the general population (sex ratio: 90 M/90F). Vertebral body length (VL) and width (VW) were significantly greater in the stenosis males and females compared to their counterparts in the control. The mean VL in the stenosis males was 31.3 mm at L1, 32.6 mm at L2, 34 mm at L3, 34.1 mm at L4, and 34.5 at L5 compared to 29.9 mm, 31.3 mm, 32.6 mm, 32.8 mm, and 32.9, respectively, in the control group (P ≤ 0.003). Additionally, the bony anterior-posterior (AP) canal diameters and cross-sectional area (CSA) were significantly smaller in the stenosis group compared to the control. The mean AP canal values in the stenosis males were 17.8 mm at L1, 16.6 mm at L2, 15.4 mm at L3, 15.6 mm at L4, and 16.1 at L5 compared to 18.7, 17.8, 16.9, 17.6, and 18.8, respectively, in the control group. Vertebral length (OR-1.273 to 1.473; P ≤ 0.002), AP canal diameter (OR-0.474 to 0.664; P ≤ 0.007), and laminar inclination (OR-0.901 to 0.856; P ≤ 0.025) were significantly associated with DLSS. Our study revealed that vertebral morphometry has a role in DLSS development.

Natural killer (NK) cells are key immune cells engaged in fighting infection and malignant transformation. In this study, we found that canine NK cell-derived exosomes (NK-exosomes) separated from activated cytotoxic NK cell supernatants express specific markers including CD63, CD81, Alix, HSP70, TSG101, Perforin 1, and Granzyme B. We examined the antitumor effects of NK-exosomes in an experimental murine mammary tumor model using REM134 canine mammary carcinoma cell line. We observed changes in tumor size, tumor initiation, progression, and recurrence-related markers in the control, tumor group, and NK-exosome-treated tumor group. We found that the tumor size in the NK-exosome-treated tumor group decreased compared with that of the tumor group in the REM134-driven tumorigenic mouse model. We observed significant changes including the expression of tumorigenesis-related markers, such as B cell-specific Moloney murine leukemia virus insertion site 1 (Bmi-1), vascular endothelial growth factor (VEGF), matrix metallopeptidase-3 (MMP-3), interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), multidrug resistance protein (MDR), tumor suppressor protein p53 (p53), proliferating cell nuclear antigen (PCNA), and the apoptotic markers, B cell lymphoma-2 associated X (Bax) and B cell lymphoma-extra large (Bcl-xL) belonging to the Bcl-2 family, in the tumor group compared with those in the control group. The expression of CD133, a potent cancer stem cell marker, was significantly higher than that of the control. By contrast, the NK-exosome-treated tumor group exhibited a significant reduction in Bmi-1, MMP-3, IL-1β, IL-6, TNF-α, Bax, Bcl-xL, and PCNA expression compared with that in the tumor group. Furthermore, the expression of CD133, which mediates tumorigenesis, was significantly decreased in the NK-exosome-treated tumor group compared with that in the tumor group. These findings indicate that canine NK-exosomes represent a promising therapeutic tool against canine solid tumors, including mammary carcinoma.

Qianghuo Shengshi decoction (QHSSD) is a classical Chinese medicine formula, which is used in clinical practice for the treatment of rheumatoid arthritis (RA) in China. However, the pharmacological mechanism of QHSSD on RA has remained unclear by now. We collected and screened active compounds and its potential targets by the pharmacology platform of Chinese herbal medicines. In addition, the therapeutic targets of RA were obtained and selected from databases. Network construction analyzed that 128 active compounds may act on 87 candidate targets and identified a total of 18 hub targets. GO annotation and KEGG enrichment investigated that the action mechanism underlying the treatment of RA by QHSSD might be involved in cell proliferation, angiogenesis, anti-inflammation, and antioxidation. Finally, molecular docking verification showed that TP53, VEGFA, TNF, EGFR, and NOS3 may be related to the RA treatment and molecular dynamics simulation showed the stability of protein-ligand interactions. In this work, QHSSD might exert therapeutic effect through a multicomponent, multitarget, and multipathway in RA from a holistic aspect, which provides basis for its mechanism of action and subsequent experiments.

IFN-γ licensing to mesenchymal stem cells (MSCs) is applied to enhance the therapeutic potential of MSCs. However, although the features of MSCs are affected by several stimuli, little information is available on changes to the therapeutic potential of IFN-γ-licensed differentiated MSCs during xenogeneic applications. Therefore, the present study is aimed at clarifying the effects of adipogenic/osteogenic differentiation and IFN-γ licensing on the in vitro immunomodulatory and migratory properties of porcine bone marrow-derived MSCs in xenogeneic applications using human peripheral blood mononuclear cells (PBMCs). IFN-γ licensing in differentiated MSCs lowered lineage-specific gene expression but did not affect MSC-specific cell surface molecules. Although indoleamine 2,3 deoxygenase (IDO) activity and expression were increased after IFN-γ licensing in undifferentiated MSCs, they were reduced after differentiation. IFN-γ licensing to differentiated MSCs elevated the reduced IDO expression in differentiated MSCs; however, the increase was not sufficient to reach to the level achieved by undifferentiated MSCs. During a mixed lymphocyte reaction with quantification of TNF-α concentration, proliferation and activation of xenogeneic PBMCs were suppressed by undifferentiated MSCs but inhibited to a lesser extent by differentiated MSCs. IFN-γ licensing increasingly suppressed proliferation of PBMCs in undifferentiated MSCs but it was incapable of elevating the reduced immunosuppressive ability of differentiated MSCs. Migratory ability through a scratch assay and gene expression study was reduced in differentiated MSCs than their undifferentiated counterparts; IFN-γ licensing was unable to enhance the reduced migratory ability in differentiated MSCs. Similar results were found in a Transwell system with differentiated MSCs in the upper chamber toward xenogeneic PBMCs in the lower chamber, despite IFN-γ licensing increased the migratory ability of undifferentiated MSCs. Overall, IFN-γ licensing did not enhance the reduced immunomodulatory and migratory properties of differentiated MSCs in a xenogeneic application. This study provides a better understanding of the ways in which MSC therapy can be applied.

We analyzed tunnel length, graft bending angle, and stress of the graft according to tunnel entry position and aspect ratio (ASR: ratio of anteroposterior depth to mediolateral width) of the articular surface for the distal femur during single-bundle outside-in anterior cruciate ligament reconstruction (ACLR) surgery. We performed multiflexible body dynamic analyses with four ASR (98, 105, 111, and 117%) knee models. The various ASRs were associated with approximately 1 mm changes in tunnel length. The graft bending angle increased when the entry point was far from the lateral epicondyle and was larger when the ASR was smaller. The graft was at maximum stress, 117% ASR, when the tunnel entry point was near the lateral epicondyle. The maximum stress value at a 5 mm distance from the lateral epicondyle was 3.5 times higher than the 15 mm entry position, and the cases set to 111% and 105% ASR showed 1.9 times higher stress values when at a 5 mm distance compared with a 15 mm distance. In the case set at 98% ASR, the low-stress value showed a without-distance difference from the lateral epicondyle. Our results suggest that there is no relationship between the ASR and femoral tunnel length. A smaller ASR causes a higher graft bending angle, and a larger ASR causes greater stress in the graft.

BACKGROUND: AKI is known to be associated with inflammation and nutritional status. The novel inflammatory prognostic score CAR (CRP/albumin ratio), which combines inflammation and nutritional status, was hypothesized to be associated with mortality in critically ill AKI patients in this study. METHODS: The included cases were patients admitted to the ICU of Shandong Provincial Hospital from January 2016 to November 2018 and diagnosed with AKI within 48 hours of ICU admission. From the electronic case database of Shandong Provincial Hospital, we extracted the baseline demographic information, vital signs, routine laboratory parameters, complications, and other data. The above records are measured within 48 hours of admission to ICU. The clinical endpoint was the total cause mortality rate in hospital and 2 years. We constructed two multivariate regression models to determine the statistically significant correlation between CAR and mortality and conducted subgroup analysis to determine the mortality among different subgroups. RESULTS: A total of 580 patients were included in this study. In multivariate regression analysis, higher CAR was associated with an increase in hospital and two-year all-cause mortality in critically ill patients with AKI after adjusting gender, age, respiratory frequency, temperature, and other confounding factors (tertile 3 versus tertile 1: OR, 95% CI: 2.97, 1.70-5.17; 3.03, 1.68-5.47, respectively; P < 0.001). Subgroup analysis showed that the CAR level in each subgroup increases with hospital mortality in critically ill patients with AKI. CONCLUSION: The increase of CAR in critically ill patients with AKI was associated with an increased risk of all-cause death.

BACKGROUND: Heterosexual transmission within serodiscordant relationships is the core source of new HIV infections. Although consistent condom use can significantly reduce HIV transmission risk among serodiscordant couples, it has not been extensively studied in Ethiopia. Consequently, the current study looked at the proportion of serodiscordant couples in Ethiopia who used condoms consistently and the factors associated with that. METHODS: A cross-sectional was conducted from October 2019 to June 2020. For the quantitative findings to be more robust and reliable, a qualitative design was incorporated. An interviewer-administered questionnaire was used to collect the data. Qualitative data were collected using gender-matched four focus group discussions. Multivariable logistic regression was conducted to identify factors associated with consistent condom use. The statistical significance of the variables was declared at a P value of less than 0.05. RESULTS: This study confirmed that the proportion of consistent condom use was 58.4% [95% CI: 53.1-63.1%]. After controlling for all other variables, unmarried partners, adjusted odds ratio (AOR) = 0.44 [95% CI: 0.229-0.877] and students and employees, AOR = 0.33 [95% CI: 0.130-0.846] and AOR = 0.39 [95% CI: 0.165-0.939], respectively, were less likely consistently use condoms, whereas couples living together, AOR = 1.86 [95% CI: 1.197-2.195], receiving counseling about condom use, AOR = 1.90 [95% CI: 1.182-3.076], and having more knowledge about HIV, AOR = 1.61 [95% CI: 1.031-2.525] were more likely to use condoms consistently. CONCLUSION: Despite its importance, the proportion of consistent condom use among serodiscordant couples was significantly low. To improve condom use consistently, planners, policymakers, and health care practitioners should consider the factors listed above when making decisions. There should be an increased focus on student and employee intervention as well.

OBJECTIVES: The aim of this study was to evaluate the shear bond strength and the nanoleakage expression of CLEARFIL Universal Bond Quick and Tetric N-Bond adhesive systems bonded to dentin. MATERIALS AND METHODS: 100 freshly extracted human premolar teeth were utilized. The teeth were sectioned to expose dentin. All dentin specimens were assigned into 4 experimental groups; 2 groups had Universal Bond Quick (Universalself group) and Tetric N-Bond (Tetricself group) applied in the self-etch mode, while 2 groups had Universal Bond Quick (Universaltotal group) and Tetric N-Bond (Tetrictotal group) applied in the total-etch mode. n = 15 for shear bond strength and n = 10 for nanoleakage experiment. One-way ANOVA and Kruskal-Wallis test were utilized to analyze the shear bond strength test and the nanoleakage expression, respectively. RESULTS: The highest significant bond strength value was recorded by the Tetricself specimens (p < 0.05) when compared to the remaining three groups. There were no statistically significant differences between the shear bond strength values recorded in the Tetrictotal, Universalself, and Universaltotal groups (p < 0.05). Both bonding systems applied in the self-etch mode (Universalself, Tetricself) had no silver nitrate deposits in the hybrid layer and the hybrid layer-adhesive interface (p < 0.001); however, both bonding systems applied in the total-etch mode (Universaltotal, Tetrictotal) had silver nitrate deposits in the hybrid layer, the hybrid layer-adhesive interface, and the bonding layer (p < 0.001). CONCLUSION: Applying the Universal Bond Quick and Tetric N-Bond in the self-etch mode exhibited better results in terms of nanoleakage expression. Universal Bond Quick showed the stability of the shear bond strength to dentin when applied using the total-etch or self-etch modes. Tetric N-Bond showed significant deterioration in bond strength when applied in the total-etch mode and exhibited the highest bond strength when applied in the self-etch mode.

PURPOSE: To assess the tear levels of inflammatory cytokines in patients with keratoconus (KC). DESIGN: Systemic review and meta-analysis. METHODS: The following electronic databases and search engine were searched: PubMed, EMBASE, Web of Science, and Google Scholar. A systematic search of all relevant studies published through January 2021 was conducted, and the standardized mean difference (SMD) and 95% confidence interval (CI) of cytokine levels were calculated to estimate the pooled effects. Sensitivity analysis, subgroup analysis, and metaregression were applied to explore the sources of heterogeneity. RESULTS: A total of 7 studies with 374 participants (374 eyes) from clinical studies were included. The tear levels of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) were significantly increased in KC compared with normal controls. The SMD of IL-1β was 1.93 (95% CI 0.22 to 3.65, P = 0.03). The SMD of IL-6 was 1.22 (95% CI 0.59 to 1.84, P < 0.001). The SMD of TNF-α was 1.75 (95% CI 0.66 to 2.83, P = 0.002). There was no significant difference between the two groups on interleukin-4 (IL-4) and interleukin-10 (IL-10). The SMD for IL-4 was 2.36 (95% CI -0.28 to 5.00, P = 0.08) and for IL-10 was 0.30 (95% CI -1.29 to 1.89, P = 0.71). Meta-regression analysis indicated that the heterogeneity maybe significantly correlated with the method of detection, the different ages, and the source of population. CONCLUSIONS: Our meta-analysis demonstrated that proinflammatory cytokines IL-1β, IL-6, and TNF-α were increased, indicating that cytokine profile changed in KC tears and inflammation may play an important role in the pathogenesis and development of KC.

Primary central nervous system lymphoma (PCNSL) is a rare lymphoma, and the disease course is often aggressive with poor prognosis outcomes. PCNSL undergoes germinal center reactions and impairs B-cell maturation. However, angiogenesis is also involved in the tumorigenesis and progression of PCNSL. This study investigated the effects of the tumor microenvironment and angiogenesis-associated genomic alterations on the outcomes of PCNSL. The analysis also evaluated the influence of treatment modality and timing on PCNSL survival using partial least squares variance-based path modeling (PLS-PM). PLS-PM can be used to evaluate the complex relationship between prognostic variables and disease outcomes with a small sample of measurements and structural models. A total of 19 immunocompetent PCNSL samples were analyzed by exome sequencing. Our results suggest that the timing of radiotherapy and mutations of ROBO1 and KAT2B are potential indicators of PCNSL outcomes and may be affected by baseline characteristics such as age and sex. Our results also showed that patients with no mutations of ROBO1 and KAT2B, SubRT subgroup showed favorable survival outcomes compared with no SubRT subgroup in short-term follow-up. All SubRT patients have received high-dose methotrexate induction chemotherapy in the initial treatment. Therefore, initial induction chemotherapy combined with subsequent radiotherapy might improve survival outcomes in PCNSL patients who have no ROBO1 and KAT2B somatic mutations in short-term follow-up. The overall findings suggest that the tumor microenvironment and angiogenesis-associated genomic alterations and treatment modalities are potential indicators of overall survival and may be affected by the baseline characteristics of PCNSL patients.

BACKGROUND: Coinfections have a potential role in increased morbidity and mortality rates during pandemics. Our investigation is aimed at evaluating the viral coinfection prevalence in COVID-19 patients. METHODS: We systematically searched scientific databases, including Medline, Scopus, WOS, and Embase, from December 1, 2019, to December 30, 2020. Preprint servers such as medRxiv were also scanned to find other related preprint papers. All types of studies evaluating the viral coinfection prevalence in COVID-19 patients were considered. We applied the random effects model to pool all of the related studies. RESULTS: Thirty-three studies including 10484 patients were identified. The viral coinfection estimated pooled prevalence was 12.58%; 95% CI: 7.31 to 18.96). Blood viruses (pooled prevalence: 12.48%; 95% CI: 8.57 to 16.93) had the most frequent viral coinfection, and respiratory viruses (pooled prevalence: 4.32%; 95% CI: 2.78 to 6.15) had less frequent viral coinfection. The herpesvirus pooled prevalence was 11.71% (95% CI: 3.02 to 24.80). Also, the maximum and minimum of viral coinfection pooled prevalence were in AMRO and EMRO with 15.63% (95% CI: 3.78 to 33.31) and 7.05% (95% CI: 3.84 to 11.07), respectively. CONCLUSION: The lowest rate of coinfection belonged to respiratory viruses. Blood-borne viruses had the highest coinfection rate. Our results provide important data about the prevalence of blood-borne viruses among COVID-19 patients which can be critical when it comes to their treatment procedure.

OBJECTIVE: To investigate the diagnostic accuracy of metagenomic next-generation sequencing (mNGS) in bronchoalveolar lavage fluid (BALF) samples or lung biopsy specimens from which suspected pulmonary tuberculosis (PTB) patients have no sputum or negative smear. MATERIALS AND METHODS: Sputum-scarce or smear-negative cases with suspected PTB (n = 107) were analyzed from January 2018 to June 2020. We collected BALF or lung tissue biopsy samples with these cases of suspected TB during hospitalization. The diagnostic accuracy of mNGS for these samples was compared with those of conventional tests or the T-SPOT.TB assay. RESULTS: 46 cases of PTB patients and 61 cases of non-PTB patients were finally enrolled and analyzed. mNGS exhibited a sensitivity of 89.13%, which was higher than conventional tests (67.39%) but equivalent to those of the T-SPOT.TB assay alone (76.09%) or T-SPOT.TB assay in combination with conventional tests (91.30%). The specificity of mNGS was 98.36%, similar to conventional tests (95.08%) but significantly higher than those of the T-SPOT.TB assay alone (65.57%) or the T-SPOT.TB assay in combination with conventional tests (63.93%). There was no significant difference in the diagnostic accuracy of mNGS in BALF samples and lung biopsy tissue specimens. CONCLUSION: Our findings demonstrate that mNGS could offer improved detection of Mycobacterium tuberculosis in BALF or lung tissue biopsy samples in sputum-scarce or smear-negative cases with suspected PTB.

BACKGROUND: This bibliometric analysis is aimed at reviewing the research pattern on the use of silver diamine fluoride (SDF) in dentistry using various citation metrics. METHODS: A well-curated search was conducted on Elsevier's Scopus database for the relevant literature on SDF published between 1969 and 2021. Bibliographic information such as information related to citations, bibliographic data, abstracts, keywords, and other relevant information was extracted using different combinations of keywords ("silver diamine fluoride" OR "Silver Diamine Fluorides" OR "Diamine Fluoride" OR "Silver Fluoride"). Analysis and visualization of the selected documents and related data were performed using various tools and software including MS Excel, MS Access, Bibexcel, VOS viewer, Biblioshiny, and Gephi. VOS Viewer was utilized for the Graph Modeling Language (GML) to generate graphical representations of the data. Furthermore, network graphs were generated to assess the various associations between research themes, countries, organizations, authors, journals, and citations. RESULTS: The initial search yielded 662 documents, of which 410 were chosen for analysis. 252 records were deemed irrelevant. The chosen records consisted of journal articles (n = 351), conference papers (n = 14), book chapters (n = 1), and review articles (n = 44). The results showed that there was an upward trend in the research on SDF, and a substantial increase was observed in the citation index after 2014. Researchers from the United States of America, Hong Kong, and Japan were the top contributors, with organizations and authors from the Faculty of Dentistry, University of Hong Kong, leading the way in citations and productivity. CONCLUSION: The bibliometric analysis provides valuable information regarding the total number of publications on SDF and their citation details. It also identifies the leading countries and organizations involved in the research on SDF and provides a comprehensive analysis of the research trends related to SDF.

BACKGROUND: Endometriosis is the most prevalent gynecological disease with elusive etiology. The mysterious entity and the lack of noninvasive diagnostic methods affect women's lives negatively. This study is aimed at finding the relationship between miR-340-5p, 92a-3p, and miR-381-3p and the pathogenesis of endometriosis in endometrial mesenchymal stem-like cells (eMSCs) of endometriosis and assessing their potential as a noninvasive biomarker in plasma. METHODS: Peripheral blood and eMSC specimens were collected from suspected women of endometriosis before laparoscopy. Total RNA was isolated from plasma and cultured eMSCs to synthesize complementary DNA. The expression of miR-340-5p, miR-92a-3p, and miR-381-3p was analyzed by RT-qPCR. To understand these miRNAs' role, we also did a bioinformatic analysis. RESULTS: There was a downregulation of miR-340-5p, miR-92a-3p, and miR-381-3p in plasma, and the upregulation of miR-340-5p and the downregulation of miR-92a-3p and miR-381-3p in eMSCs of women with endometriosis. There was a positive concordance between the expression of miR-92a-3p and miR-381-3p in plasma and eMSCs. Our study also showed three genes, Solute Carrier Family 6 Member 8 (SLC6A8), Zinc Finger Protein 264 (ZNF264), and mouse double minute 2 (MDM2), as common targets of these miRNAs. CONCLUSIONS: This study has been one of the first attempts to examine the expression of miR-340-5p, miR-92a-3p, and miR-381-3p in both plasma and eMSCs and revealed their possible role in endometriosis based on in silico analysis. Biomarkers pave the way to develop a new therapeutic approach to the management or treatment of endometriosis patients. Our result as a first report shows that combined levels of miRNAs 340-5p and 381-3p may have the potential to be utilized as diagnostic biomarkers for endometriosis.

Studies on green biosynthesis of newly engineered nanoparticles for their prominent medicinal applications are being the torch-bearing concerns of the state-of-the-art research strategies. In this concern, we have engineered the biosynthesized Luffa acutangula silver nanoparticles of flavonoid O-glycosides in the anisotropic form isolated from aqueous leave extracts of Luffa acutangula, a popular traditional and ayurvedic plant in south-east Asian countries. These were structurally confirmed by Ultraviolet-visible (UV-Vis), Fourier transform infrared spectroscopy accessed with attenuated total reflection (FTIR-ATR) spectral analyses followed by the scanning electron microscopic (SEM) and the X-ray diffraction (XRD) crystallographic studies and found them with the face-centered cubic (fcc) structure. Medicinally, we have explored their significant antioxidant (DPPH and ABTS assays), antibacterial (disc diffusion assay on E. coli, S. aureus, B. subtilis, S. fecilis, and S. boydii), and anticancer (MTT assay on MCF-7, MDA-MB-231, U87, and DBTRG cell lines) potentialities which augmented the present investigation. The molecular docking analysis of title compounds against 3NM8 (DPPH) and 1DNU (ABTS) proteins for antioxidant activity; 5FGK (Gram-Positive Bacteria) and 1AB4 (Gram-Negative Bacteria) proteins for antibacterial activity; and 4GBD (MCF-7), 5FI2 (MDA-MB-231), 1D5R (U87), and 5TIJ (DBTRG) proteins for anticancer activity has affirmed the promising ligand-protein binding interactions among the hydroxy groups of the title compounds and aspartic acid of the concerned enzymatic proteins. The binding energy varying from -9.1645 to -7.7955 for Cosmosioside (1, Apigenin-7-glucoside) and from -9.2690 to -7.8306 for Cynaroside (2, Luteolin-7-glucoside) implies the isolated compounds as potential bioactive compounds. In addition, the performed studies like QSAR, ADMET, bioactivity properties, drug scores, and toxicity risks confirmed them as potential drug candidates and aspartic acid receptor antagonists. This research auxiliary augmented the existing array of phytological nanomedicines with new drug candidates that are credible with multiple bioactivities.

This study explored the association between family cohesion and self-perceived need for dental treatment among adolescents. A school-based representative cross-sectional study was conducted with 746 students aged 15 to 19 randomly selected from schools in Campina Grande, Brazil. Parents/guardians provided information on sociodemographic data, and students completed questionnaires about the self-perceived need for dental treatment, dental pain, and family cohesion and adaptability (FACES III). Two dentists were trained (kappa >0.80) to diagnosis dental caries using the Nyvad criteria and assess adolescents' level of functional oral health literacy (BREALD-30). Descriptive analysis was performed, followed by nonadjusted and adjusted robust binary logistic regression for complex samples (α = 5%). The prevalence of self-perceived need for dental treatment was 88.6%. The presence of dental caries (OR = 2.10; IC 95%: 1.22-3.61), tooth loss (OR = 15.81; IC 95%: 2.14-116.56), dental pain in the last six months (OR = 1.87; IC 95%: 1.06-3.31), and enmeshed family cohesion type (OR = 10.23; IC 95%: 3.96-26.4) remained associated with the self-perceived need for dental treatment in the final model. In conclusion, dental caries, dental pain, tooth loss, and family cohesion influenced the self-perceived need for dental treatment in adolescents.

The aim of the present study was to examine (a) the relationship of body fat (BF) assessed by bioimpedance analysis (BIA) and skinfold thickness (SKF) and (b) the variation of BF by age depending on the assessment method. Participants were 32 women and 134 men recreational marathon runners, who were tested for BF using both assessment methods (BIA and SKF). Rc between BIA and SKF assessment methods was 0.803 (95% CI; 0.640, 0.897) in women and 0.568 (95% CI; 0.481, 0.644) in men. A large main effect of the assessment method on BF was observed (p < 0.001, η 2 = 0.156) with SKF presenting higher BF than BIA by 2.9%. The difference between SKF and BIA was 3.9 ± 2.7% (95% confidence intervals, CI; 3.4; 4.3, p < 0.001) in men, whereas no difference was found in women (-0.9 ± 2.9%; 95% CI; -1.9; -0.2, p = 0.101). BF correlated with age with small magnitude (BIA, r = 0.18, p = 0.036; SKF, r = 0.23, p = 0.007) in men, i.e., the older the age, the higher the BF. A similar trend of moderate magnitude was observed in women for BIA (r = 0.45, p = 0.011), but not for SKF (r = 0.33, p = 0.067). In conclusion, practitioners involved in the training of recreational runners would be advised to consider that BIA elicits a lower BF value than the SKF method in men.

Recent studies have found that cytoskeleton-associated protein 2 like (CKAP2L), an important oncogene, is involved in the biological behavior of many malignant tumors, but its function in the malignant course of glioma has not been confirmed. The main purpose of this study was to clarify the relationship between prognostic clinical characteristics of glioma patients and CKAP2L expression using data collected from the GEPIA, HPA, CGGA, TCGA, and GEO databases. CKAP2L expression was significantly increased in glioma. Further, Kaplan-Meier plots revealed that increased expression of CKAP2L was associated with shorter survival time of glioma patients in datasets retrieved from multiple databases. Cox regression analysis indicated that CKAP2L can serve as an independent risk factor but also has relatively reliable diagnostic value for the prognosis of glioma patients. The results of gene set enrichment analysis suggested that CKAP2L may play a regulatory role through the cell cycle, homologous recombination, and N-glycan biosynthesis cell signaling pathways. Several drugs with potential inhibitory effects on CKAP2L were identified in the CMap database that may have therapeutic effects on glioma. Finally, knockdown of CKAP2L inhibited the proliferation and invasion of cells by reducing the expression level of cell cycle-related proteins. This is the first study to demonstrate that high CKAP2L expression leads to poor prognosis in glioma patients, providing a novel target for diagnosis and treatment of glioma.

The present study was designed to compare the body composition and indicators of chronic inflammatory grade, such as leptin, adiponectin, and resistin concentrations in irregularly active and active SCI subjects. Thirty-two male subjects participated in this study. They were divided into three groups: able-bodied control irregularly active (control, n = 11), irregularly active with SCI (SCI-IA, n = 8), and physically active with SCI (SCI-PA, n = 13). The enzyme-linked immunosorbent assay (ELISA) assessed serum concentrations of leptin, adiponectin, and resistin. All volunteers performed the maximum oxygen uptake (VO2max) test, 24 h total energy expenditure (TEE), and body composition by skinfold thicknesses. Leptin concentrations were higher in the SCI-IA group when compared to the other groups, while no significant differences were found between the SCI-PA and control cohorts. In addition, no significant differences were found among groups for serum adiponectin and resistin concentrations either. The SCI-PA group showed significantly higher values for TEE and VO2max when compared to the other groups. Percentages of body fat and circumference were decreased in the control and SCI-PA groups when compared to the SCI-IA cohort. Associations between leptin and cardiorespiratory capacity and anthropometric markers were also observed. Our findings highlight that the lack of physical activity in the SCI subjects leads to poor general physical fitness and higher levels of body adiposity, which may induce hyperleptinemia, an essential marker for cardiometabolic disorders.

Ether lipids are overexpressed in malignant tumor and play an important role in tumor process. Glioma is the most common malignant central nervous system tumor, and the content of ether lipids is higher than that of normal tissues. Alkylglycerone phosphate synthase (AGPS) is a key enzyme in the synthesis of ether esters and plays a vital role in maintaining the morphology and pathogenic properties of tumor cells. The cell proliferation and the content of tumor-related lipid such as monoalkylglycerol ether (MAGe), lysophosphatidic acid ether (LPAe), lysophosphatidylcholine ether (LPCe), lysophosphatidylethanolamine ether (LPEe), phosphatidyl inositol (PI), phosphatidylcholine (PC), and phosphatidylserine (PS) were suppressed after AGPS silencing in U251, H4, and TJ905 cells; however, heterogeneous nuclear ribonucleoprotein K (HNRNPK) could reverse the above phenomenon such as cellar proliferation and ether lipid secretion. We found that HNRNPK was the target protein of AGPS by coimmunoprecipitation and mass spectrometry assay and verified by western blot assay in U251 cells. It confirmed that AGPS and HNRNPK are coexpressed in the cellular nucleus by a confocal laser microscope. The main protein-protein interaction mechanism between AGPS and HNRNPK is hydrogen bond, conjugation bond, hydrophobic bond, and electrostatic force by computer simulation prediction.

INTRODUCTION: The aim of this study was to assess the risk factors for falls in patients with Parkinson's disease. MATERIALS AND METHODS: The study comprised 53 participants (52.8% women and 47.2% men). The Hoehn and Yahr 5-point disability scale was used to assess the severity of Parkinson's disease. The Tinetti Balance and Gait Scale were used to evaluate the risk of falls. The Katz scale was used to test the independence of people with PD. The Falls Efficacy Scale-International Short Form (FES-I) was implemented to assess fear of falling. RESULTS: The majority of participants was at a high risk of falls, being at the same level for women and men. A significant relationship was noted between the risk of falls and subjective assessment of mobility (χ 2 = 31.86, p < 0.001), number of falls (χ 2 = 37.92, p < 0.001), independence of the subjects (χ 2 = 19.28, p < 0.001), type of injury suffered during the fall (χ 2 = 36.93, p < 0.001), external factors (χ 2 = 33.36, p < 0.001), and the level of fear of falling (χ 2 = 8.88, p < 0.001). A significant relationship also occurred between the number of falls and the fear of falling (χ 2 = 33.49, p < 0.001) and between the number of falls and disease severity (χ 2 = 45.34, p < 0.001). The applied physiotherapy did not reduce the risk of falls (χ 2 = 3.18, p = 0.17). CONCLUSIONS: Individuals who rated their mobility as good or excellent were at a low risk of falls. People who fell more times were at a high risk of falling. People more independent were at a low risk of falls. Previous injuries were the most associated with being at risk of falling. Uneven surfaces and obstacles on one's path are the external factors most associated with the risk of falling. People with low levels of fall anxiety were at a low risk of falls. Most people with low fall anxiety have never fallen. Additionally, the majority of patients with stage 1 of the disease have not fallen at all. The reason for the ineffectiveness of physiotherapy may be due to the exercise programs used and the lack of systematic implementation of them. PD is different for each patient; thus, it is important to select individually customized physiotherapy depending on motor and nonmotor symptoms, as well as general health of a patient.

OBJECTIVE: Aging is a growing public health concern for people, organizations, and governments. The current study was undertaken to provide insights into the global research output on geriatric nursing. METHODS: A bibliometric study was implemented using the WoS database for the period from 1900 to 2020. Various tools and measures were used to analyze and visualized. RESULTS: The search strategy found 4923 papers. The oldest paper was written by Beverly C. Andre in 1953. As team size increases, so does the number of citations. The USA was the active country and the highest number of coauthors. New York University was an active institution. Stig Karlsson was the most active author in Geriatric Nursing with 28 articles from Sweden, followed by Koen Milisen and Sandman, with 26 articles each from Sweden and Belgium. The most frequent words in this field were depression, malnutrition, education, Alzheimer's disease, and dementia. The latest research themes in this field were COVID-19, interprofessional locomotive syndrome, emergency nursing, and public health. The most influential papers were specified. Journal of the American Geriatrics Society was the most active journal. CONCLUSIONS: Geriatric nursing is a rooted field and has received special attention in the last decade. Policymakers, especially in developing countries, should pay attention to geriatric nursing as a specialty of nursing to solve aging issues they would face considering the increasing elderly population.

OBJECTIVE: To test the biomechanical properties of 3D printed tantalum and titanium porous scaffolds. METHODS: Four types of tantalum and titanium scaffolds with four alternative pore diameters, #1 (1000-700 μm), #2 (700-1000 μm), #3 (500-800 μm), and #4 (800-500 μm), were molded by selective laser melting technique, and the scaffolds were tested by scanning electronic microscope, uniaxial-compression tests, and Young's modulus tests; they were compared with same size pig femoral bone scaffolds. RESULTS: Under uniaxial-compression tests, equivalent stress of tantalum scaffold was 411 ± 1.43 MPa, which was significantly larger than the titanium scaffolds (P < 0.05). Young's modulus of tantalum scaffold was 2.61 ± 0.02 GPa, which was only half of that of titanium scaffold. The stress-strain curves of tantalum scaffolds were more similar to pig bone scaffolds than titanium scaffolds. CONCLUSION: 3D printed tantalum scaffolds with varying pore diameters are more similar to actual bone scaffolds compared with titanium scaffolds in biomechanical properties.

Thyroid transcription factor-1 (TTF-1/NKx2.1) is a member of the NKx2 tissue-specific transcription factor family, which is expressed in thyroid follicle, parathyroid gland, alveolar epithelium, and diencephalon which originated from ectoderm, and participates in the differentiation, development, and functional maintenance of the above organs. Recent studies have shown that the abnormal expression of TTF-1 is closely related to the occurrence of a variety of human diseases and can be used as a potential new target for the diagnosis and treatment of related diseases. In this article, in order to strengthen the systematic understanding of TTF-1 and promote the progress of related research, we reviewed the structure, expression regulation, biological functions of TTF-1, and its role in the occurrence and development of human-related clinical diseases. Meanwhile, we prospect the future research direction of TTF-1, which might ultimately contribute to the understanding of the pathogenesis of related clinical diseases and the development of new prevention and treatment strategies.

To evaluate the applicability of bisulfate conversion-free methylation assay based on enzyme digestion in fecal screening for colorectal cancer (CRC). Stool samples were collected from a total of 1142 participants with intestinal abnormalities, including 180 positive cases, 60 advanced adenomas, and 902 negative cases. DNA from reference cell lines and clinical samples was extracted and digested with an enzyme to detect the methylation of CRC markers SEPT9, SDC2, NDRG4, SFRP2, and BMP3 genes. Statistical analysis was then used to determine the ability of the markers, both individually and in combination, to detect CRC and adenoma. Our results showed that the enzyme digestion method could suitably detect DNA marker methylation in as low as 1% of the cell lines. BMP3 had a considerably low detection rate in all clinical samples, with only 6 positive cases detected out of 180 cancer samples. Our findings showed that the combination of SEPT9, SDC2, and SFRP2 had an area under the receiver operation curve of 0.937, sensitivity of 94.11%, and specificity of 89.21% for detecting CRC. Moreover, the detection sensitivity of adenoma can also reach 38.33%. After innovatively utilizing bisulfate conversion-free methylation assay for CRC screening, this study verified the potential clinical applicability of combining multiple biomarkers for CRC screening in a large number of samples.

Arsenic (As) toxicity has deleterious effects on human health causing disorder in the brain. The aim of this study was to investigate the possible neuroprotective effect of resveratrol (RSV) on arsenic-induced neurotoxicity in rats. Neurotoxicity in rats was developed by treating As 10 mg/kg/day for 21 days orally. Animals were put into seven groups: control, vehicle, As, As+RSV10, As+RSV20 mg/kg, RSV10, and RSV20 mg/kg. Behavioral assessments such as the social interaction test, novel object recognition test, elevated plus maze, open field, the Morris water maze, in addition to assessment of biomarkers such as ferric reducing ability of plasma assay, glutathione assay, and malondialdehyde assay, were used to evaluate the effects of RSV on cognitive impairment and molecular changes induced by As. The results showed that cognitive performance impaired in As rats. RSV20 mg/kg significantly could ameliorate behavioral changes like spatial learning in days 3 and 4 (p < 0.05), recognition learning and memory (p < 0.01), disabilities in motor coordination and stress (p < 0.05), increased anxiety (p < 0.05), and social interaction deficit (sociability (p < 0.001) and social memory (p < 0.05)). RSV20 mg/kg also attenuated molecular modifications like decreased antioxidant power (p < 0.001), reduced glutathione content (p < 0.05), and increased malondialdehyde level (p < 0.05) induced by As. In addition to oxidative stress assessments, RSV10 mg/kg could significantly increase FRAP (p < 0.01) and GSH (p < 0.05); however, MDA was not significantly increased. Our current behavioral findings suggest that RSV has neuroprotective effects against AS toxicity.

MATERIALS AND METHODS: This cross-sectional study was performed on patients with pemphigus vulgaris referred to Faghihi Hospital and Shiraz Dental Faculty in 2017-2018. The participants included 26 women with histopathologically confirmed pemphigus vulgaris and 26 healthy age-matched controls. The serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estrogen, progesterone, testosterone, prolactin, dehydroepiandrosterone (DHEA), and dihydrotestosterone (DHT) were evaluated in both groups. Independent t-test and two-way ANOVA were used for data analysis. RESULTS: The mean age of the patients was 49.88 ± 10.46 years and that of the control group was 49.92 ± 11.30 years. Unlike the case group, the DHEA serum level was significantly higher among nonmenopausal participants in the control group. Moreover, the levels of testosterone and DHEA were significantly lower in the case group in comparison to the control group (p = 0.015 and p = 0.026, respectively). CONCLUSION: Considering the effects of age and menopause, the serum levels of testosterone and DHEA were significantly lower in the patients with pemphigus vulgaris than in the healthy controls. Hence, these hormones might have a role in the pathogenesis of pemphigus vulgaris.

With the increasing application of music therapy in clinical practice, the effectiveness of music therapy in improving the negative emotions of patients, relieving pain, and adjusting the physiological state has also been receiving increasing recognization. Moreover, music therapy as adjuvant therapy for conventional treatment can achieve a better improvement in patient satisfaction and facilitate the acceptance of make music therapy by the medical industry. In addition to inevitable trauma, general surgery is criticized for its long treatment cycles and postoperative pain. With the continuous development of fast-track surgery (FTS), music therapy has received more attention in general surgical treatment. This study reviews the development history and prospects of music therapy in general surgery.

Xianling Gubao Capsule (XGC), a kind of capsule preparation of Chinese herbal officially approved for sale by the National Medical Products Administration (NMPA), has the effect of tonifying kidney and strengthening bones. Although the impact of XGC in treating bone diseases has been widely studied, the effect of XGC in kidney injury is unknown yet. The kidney injury model is established by intraperitoneal injection with cadmium chloride (CdCl2). Before model establishment, each XGC group was pregavaged with XGC for 10 d. After 10 d, CdCl2 was injected intraperitoneally into the model group and each XGC group, each XGC group continued to be gavaged with XGC for 4 weeks, and the control group was gavaged with equal doses of distilled water once daily. The level of serum urea nitrogen (BUN) and serum creatinine (Cr) is evaluated by kit. The effect of XGC on protecting kidney injury in mice with kidney injury is analyzed by histopathology (HE stain), immunohistochemistry (IHC), and real-time fluorescence quantitative PCR (RT-qPCR). The results show that CdCl2 significantly increases the level BUN and Cr in serum and results in remarkable pathological changes in the nephron, including tubule edema, congestion, and necrosis. While oral administration of XGC can significantly decrease BUN and Cr in serum and prevent and protect the kidney from the above injuries. In addition, the protein expression of p-mTOR was remarkably reduced, and the ratio of LC3II/LC3I protein and mRNA was significantly increased in mice with oral administration of XGC. Our findings suggest that XGC can prevent and protect kidney injury by improving the state of renal tubular hyperemia and necrosis and reduce the level of BUN and Cr in cadmium poisoning mice.

Physical activity is an important factor for primary and secondary stroke prevention. The process of stroke rehabilitation includes early and late physical activity and exercise, which prevents further stoke and improve patients' quality of life. MY WAY project, an ERASMUS+ SPORT program, is aimed at analyzing and developing or transferring best innovative practices related to physical activity and exercise enhancing health in poststroke patients. The aim of the study was to identify, analyze, and present the good practices and strategies to encourage participation in sport and physical activity and engage and motivate chronic stroke patients to perform physical activity changing their lifestyle and to maintain a high adherence to long-term exercise-based rehabilitation programs. Our results demonstrated that unified European stroke long-term exercise-based rehabilitation guidelines do not exist. It seems that low training frequency with high aerobic exercise intensity may be optimal for improved physical performance and quality of life in combination with a high adherence. It is important to optimize the training protocols suitable for each patient. The continuous education and training of the specialized professionals in this field and the presence of adequate structures and cooperation between different healthcare centers are important contributors. The clear objective for each country should be to systematically make the necessary steps to enhance overall exercise-based stroke rehabilitation attendance in the long term. Long-term interventions to support the importance of physical exercise and lifelong exercise-based rehabilitation in chronic stroke patients should be created, what coincides with the goal of the MY WAY project.

During disc degeneration, the increase of inflammatory cytokines and decrease of disc cell density are two prominent features. Enhanced inflammatory reaction contributes to disc annulus fibrosus (AF) cell apoptosis. In this study, we investigated whether resveratrol can suppress AF cell apoptosis in an inflammatory environment. Rat disc AF cells were cultured in medium with or without tumor necrosis factor-α (TNF-α). Resveratrol was added along with the culture medium supplemented with TNF-α. Caspase-3 activity, cell apoptosis ratio, expression of apoptosis-associated molecules (Bcl-2, Bax, caspase-3, cleaved PARP, and cleaved caspase-3), reactive oxygen species (ROS) content, and the total superoxide dismutase (SOD) activity were measured. Our results showed that TNF-α significantly increased caspase-3 activity and AF cell apoptosis ratio and upregulated gene/protein expression of Bax, caspase-3, cleaved caspase-3, and cleaved PARP, whereas it downregulated the expression of Bcl-2. Moreover, TNF-α significantly increased ROS content but decreased the total SOD activity. Further analysis demonstrated that resveratrol partly attenuated the effects of TNF-α on AF cell apoptosis-associated parameters, decreased ROS content, and increased the total SOD activity in the AF cells treated with TNF-α. In conclusion, resveratrol attenuates inflammatory cytokine TNF-α-induced AF cell apoptosis through regulating oxidative stress reaction in vitro. This study sheds a new light on the protective role of resveratrol in alleviating disc degeneration.

The purpose of this study is to describe the results of clonazepam use in the treatment of phantom limb pain (PLP). Although the efficacy of clonazepam on PLP has been reported in 1996, there are no subsequent known studies that confirmed this report. A consecutive sample of 32 patients who suffered from PLP after recent lower limb amputation was studied based on clinical charts. Wilcoxon's signed rank test was used to compare Numeric Rating Scale (NRS) values before and after the treatment with clonazepam. Twenty-three amputees were treated only with clonazepam, without adding other drugs or targeted rehabilitation treatments. The median NRS before the treatment with clonazepam was 7 (2), the median NRS after 31 ± 5 days of treatment was 3 (3.5) (p < 0.0001). The average dosage of clonazepam used was 1.5 ± 1 mg per day. The results suggest that clonazepam has to be considered as an alternative drug for PLP treatment.

BACKGROUND: Exosomes as extracellular vesicles (EVs) are nanoscale intercellular messengers secreted from cells to deliver biological signals. Today, exosomes have become a new field of research in regenerative medicine and are considered as potential therapies to control inflammation and wound healing and enhance and improve healing in many diseases. Given the global burden of osteoarthritis (OA) as the fastest-growing health condition and one of the major causes of physical disability in the aging population, research to establish EVs as therapeutic products can meet the basic clinical needs in the management of osteoarthritis and provide a therapeutic solution. OBJECTIVES: The present study is aimed at evaluating the regenerative potentials of the exosomes secreted from adipose and bone marrow tissue-derived mesenchymal stem cells (AD- and BM-MSCs) in ameliorating the symptoms of OA. METHOD: In this experimental study, AD- and BM-MSCs were isolated and cultured in the laboratory until passage 3. Finally, these cells' secreted exosomes were isolated from their conditioned medium. Ciprofloxacin-induced OA mouse models underwent intra-articular injection of exosomes from AD-MSCs and BM-MSCs. Finally, the expression levels of collagen I and II, sox9, and aggrecan genes using real-time PCR, histological analysis, and immunohistochemical (IHC) studies were performed. RESULTS: Real-time PCR data showed that although the expression level of collagen type II was lower in both exosome-treated groups than the normal, but it was significantly increased in comparison with the sham and OA, with higher expression in BM-Exo rather than AD-Exo group. Similarly, the histological staining and IHC results have provided almost identical data, emphasizing on better therapeutic effect of BM-MSCs-exosome than AD-MSCs-exosome. CONCLUSION: BM-MSCs secreted exosomes in comparison with AD-MSCs could be considered as a better therapeutic option to improve osteoarthritis and exhibit potential as a disease-modifying osteoarthritis cell-free product.

METHODS: The expression level of GRWD1 in human cancer tissues was analyzed using the Tumor Immune Evaluation Resource (ver. 2.0, TIMER2), Gene Expression Profiling Interactive Analysis (ver. 2, GEPIA2), and UALCAN databases. The Kaplan-Meier plotter was utilized to analyze the survival data. Spearman's correlation analysis was used to find out the correlation between the expression level of GRWD1 and predictive biomarkers, such as tumor mutation burden (TMB) and microsatellite instability (MSI). Furthermore, the MEXPRESS website was used to study the potential relationship between DNA methylation level of GRWD1 and pathological staging. We utilized the "immune" module provided on the TIMER2 website to explore the relationship between the expression level of GRWD1 and immune infiltration in all types of cancer in TCGA. Pearson's correlation analysis was used to investigate the correlation between the expression level of GRWD1 and the expression levels of immune checkpoint-related genes. For protein expression analysis, we used the CPTAC module provided by the UALCAN portal to compare the total protein and phosphorylated protein level of GRWD1 in adjacent normal and tumor tissues. RESULTS: GRWD1 was overexpressed in tissues of most types of cancer, in which the expression levels of GRWD1 in the kidney chromophobe (KICH), kidney renal papillary cell carcinoma (KIRP), and kidney renal clear cell carcinoma (KIRC) tissues showed an opposite trend, and the expression level of GRWD1 was correlated to only the KIRC tumor stage. The results of survival analysis showed that the expression level of GRWD1 was significantly associated with overall survival in six types of cancer and disease-free survival (DFS) in three types of cancer. Importantly, the increased expression level of GRWD1 was strongly correlated with prognosis of KIRC patients. There was a positive relationship between the expression level of GRWD1 and immune cell infiltration in several types of cancer, and the expression level of GRWD1 was also positively correlated with TMB, MSI, and DNA methylation in some types of cancer. The results of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that "ubiquitin mediated proteolysis," "spliceosome," and "nucleotide excision repair" were involved in the effect of GRWD1 expression on tumor pathogenesis. CONCLUSION: This pancancer analysis provided a comprehensive overview of the carcinogenic effects of GRWD1 on a variety of human cancers. The results of bioinformatics analysis indicated GRWD1 as a promising biomarker for detection, prognosis, and therapeutic assessment of diverse types of cancer, and GRWD1 could act as a tumor suppressor in KIRC.

PURPOSE: Oblique lumbar interbody fusion (OLIF) approach has been increasingly frequently performed in recent years. However, neither studies of OLIF approach nor the researches of the application of enhanced recovery after surgery (ERAS) in spinal surgery are relatively rare. Here, our study is aimed at investigating the therapeutic effects of the application of OLIF compared with transforaminal lumbar interbody fusion (TLIF) approach combined with ERAS in dealing with this disorder at short-term follow-up. Material and Methods. Thirty-eight patients who undergone OLIF and forty patients who undergone TLIF with pedicle screws were included in our study. The concept of ERAS was applied in the perioperative period of the patients. Preoperative and postoperative laboratory test indexes of blood were examined and evaluated in all individuals. Visual analogue scale (VAS), Oswestry disability index (ODI), and Clinical Symptom Score of the Japanese Orthopaedic Association (JOA) were used in preoperative evaluation and postoperative follow-up. Satisfaction survey was also performed after surgery. RESULT: The postoperative results of red blood count, C-reaction protein, D-dimer, and albumin were still within the reference ranges in most of the patients. It was shown that objective evaluations including VAS score, ODI index, and JOA score were significantly improved after OLIF and TLIF surgery. The follow-up of 6 months after surgery showed that VAS, ODI, and JOA were improved more in the OLIF group than that in the TLIF group. The overall satisfaction (satisfied and very satisfied) was 95% and 97.4% in the TLIF group and the OLIF group, respectively, and there was no difference between the two groups. CONCLUSION: This study indicated that OLIF and TLIF approach were both rather effective therapies for patients with lumbar degenerative diseases. The effect of OLIF procedure could be better than TLIF procedure in the early stage after surgery.

Tumor-infiltrating immune cells have been implicated in the tumorigenesis and progression of esophageal squamous cell carcinoma (ESCC). However, the functionalities and clinical significance of immune cells remain largely unveiled. In this study, the gene expression data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were extracted. The relative infiltrating levels were estimated by single-sample gene set enrichment analysis. Some cytotoxic immune cells were attenuated, and resting cytotoxic immune cells were accumulated in ESCC. Remarkably, we also observed that infiltrating levels of macrophage M2 and resting natural killer (NK) cells were increased in nonresponders of CRT, and T cells that had anticancer activities such as activated memory CD4 and T helper 2 (Th2) cells were significantly reduced in ESCC tissues of the nonresponders. Moreover, the high infiltrations of the resting natural killer (NK) and dendritic cell (DC) were observed to result in a shorter overall survival in ESCC. Consistently, high expression of immune checkpoint genes, CTLA4 and HAVCR2, was associated with poor prognosis. Furthermore, STAT5B, a key transcription factor, as well as its target genes, involved in the regulation of T cells, was significantly downregulated in ESCC, especially subgroup I, indicating that downregulation of STAT5B might be associated with reduced T cell-mediated anticancer activity. In conclusion, the present study significantly improved our understanding of the regulatory roles of immune cells in ESCC.

Chronic morphine intake for treating various pain is frequently concomitant with morphine-induced hyperalgesia and tolerance. The mechanisms can be explained by the activation of p38-MAPK proteins in microglia in the spinal cord horn. Exercise has been shown to prevent the development of microglia overactivation. Thus, we designed to test whether exercise prevents the morphine-induced hyperalgesia and tolerance as well as suppression of p38 phosphorylation. A p38 inhibitor SB203580, exercise, and exercise preconditioning were used for treating morphine-induced hyperalgesia and tolerance development in the present study. The behavior tests for hyperalgesia and tolerance were performed in male Wistar rats before and after morphine administration. Western blotting and immunostaining for examining phosphorylated-p38 expression were performed after the behavior tests. Our results showed that SB203580 and exercise, but not exercise preconditioning, prevented the occurrence of morphine-induced hyperalgesia and tolerance. Meanwhile, exercise decreased morphine-induced phosphorylated-p38 overexpression. In summary, exercise prevented the development of morphine-induced hyperalgesia and tolerance. The mechanism may be related to inhibition of p38 phosphorylation.

METHOD: We search the PubMed, Embase, Google Scholar, and Wanfang (China) databases (up to December 1, 2020) to identify all eligible publications. The pooled odds ratio (OR) correspondence with 95% confidence interval (CI) was calculated to evaluate the associations. RESULTS: Finally, nine eligible studies with 7,157 cases and 6,440 controls and five studies with 2,278 cases and 2,821 controls were enrolled in rs3877899 and rs7579 polymorphisms, individually. However, a null significant association was detected between the two polymorphisms in SEPP1 and susceptibility to colorectal, breast, and prostate cancer in all comparison models. Subsequently, subgroup analysis based on tumor type, no significant association was identified for prostate, breast, and colorectal cancer. In addition, when the stratification analyses were conducted by the source of control, HWE status, and ethnicity, yet no significant association was found. CONCLUSIONS: The current meta-analysis shows that SEPP1 rs3877899 and rs7579 polymorphisms may not be associated with susceptibility to colon cancer, breast cancer, and prostate cancer, and further well-designed studies with a larger sample size are warranted to validate our findings.

Adaptation is an important factor for the clinical success of restorations. However, no studies are available evaluating the adaptation of primary crowns. The aim of this study was to compare the adaptation of crowns fabricated by CAD/CAM technology versus prefabricated fiberglass primary crowns. Typodont maxillary central, canine, and mandibular molar teeth were prepared to serve as master dies after the size of Figaro crowns was determined (n = 10). Master dies were scanned with an intraoral scanner, and 10 identical CAD/CAM crowns were fabricated from resin-ceramic blocks. Figaro and CAD/CAM crowns were placed on the corresponding master dies and scanned via micro-CT. Three-dimensional volumetric gap measurements were performed to evaluate the overall adaptation. A total of 255 location-based linear measurements were allocated into 4 categories: marginal, cervical-axial, middle-axial, and occlusal. Statistical analyses were performed with factorial ANOVA, repeated measure ANOVA, and LSD tests (α = 0.05). CAD/CAM crowns showed significantly lower overall and location-based gap measurements than Figaro crowns regardless of tooth number (p < 0.05). For all groups, mean marginal discrepancies were lower than occlusal measurements (p < 0.05). Both crown types showed higher marginal gaps for molar teeth than for canine and central incisors with no significant difference between them (p > 0.05). CAD/CAM-fabricated crowns showed better marginal and internal adaptation than prefabricated Figaro crowns.

INTRODUCTION: Child obesity is recognized as one of the major public health problems globally, which demands multicomponent and comprehensive interventions. The objective of this systematic review is to evaluate, synthesize, and combine the existing evidence of various setting-based interventions across developed and developing countries that aim to prevent childhood obesity. METHODS: An electronic and systematic search was conducted on setting-based interventions related to childhood obesity both in developed and developing countries. A study was considered eligible if it was a randomized controlled trial that focused on home-based, school-based, or community-based intervention for childhood obesity and published in English from 2010 to 2020. A wide range of electronic bibliographic databases, such as PubMed, Medline, Embase, and ERIC were searched. The various studies were carried out among children aged 4-18 years old. A total of 32 studies were identified; out of which 24 were school-based interventions, and the remaining were nonschool-based. RESULTS: The studies in this review highlighted important school and nonschool-based interventions to avoid obesity among children and adolescents. School-based interventions that had considered both physical activity (PA) and diet along with home elements showed great effectiveness. These findings reveal that the specific intervention components such as nutrition education curriculum, prolonged time for PA, and upgrading self-efficacy of study participants should be considered to prevent obesity across developed and developing countries. However, the findings from nonschool-based interventions were restricted by the scarcity of the studies. CONCLUSION: Multisetting and multipronged strategies are required to avoid or reduce childhood obesity across the globe. However, additional studies are needed with a large sample size. Further study designs based on theory should be conducted in nonschool settings for the creation of meaningful and detailed guidelines that can support the prevention of obesity in children.

As the main economic crop cultivated in the Yellow River Delta, winter jujube contains various nutrients. However, soil salinization and fungal diseases have affected the yield and quality of winter jujube. In order to use plant growth-promoting rhizobacteria (PGPR) to reduce these damages, the antagonistic bacteria CZ-6 isolated from the rhizosphere of wheat in saline soil was selected for experiment. Gene sequencing analysis identified CZ-6 as Bacillus amyloliquefaciens. In order to understand the salt tolerant and disease-resistant effects of CZ-6 strain, determination of related indicators of salt tolerance, pathogen antagonistic tests, and anti-fungal mechanism analyses was carried out. A pot experiment was conducted to evaluate the effect of CZ-6 inoculation on the rhizosphere microbial community of winter jujube. The salt tolerance test showed that CZ-6 strain can survive in a medium with a NaCl concentration of 10% and produces indole acetic acid (IAA) and 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase. Studies on the inhibition mechanism of pathogenic fungi show that CZ-6 can secrete cellulase, protease, and xylanase. Gas chromatography-mass spectrometry (GC-MS) analysis showed that CZ-6 can release volatile organic compounds (VOCs), including 2-heptanone and 2-nonanone. In addition, the strain can colonize the rhizosphere and migrate to the roots, stems, and leaves of winter jujube, which is essential for plant growth or defense against pathogens. Illumina MiSeq sequencing data indicated that, compared to the control, the abundance of salt-tolerant bacteria Tausonia in the CZ-6 strain treatment group was significantly increased, while the richness of Chaetomium and Gibberella pathogens was significantly reduced. Our research shows that CZ-6 has the potential as a biological control agent in saline soil. Plant damage and economic losses caused by pathogenic fungi and salt stress are expected to be alleviated by the addition of salt-tolerant antagonistic bacteria.

Hermansky-Pudlak syndrome (HPS) is a rare genetic disorder with an autosomal recessive inherited pattern. It is mainly characterized by deficiencies in lysosome-related organelles, such as melanosomes and platelet-dense granules, and leads to albinism, visual impairment, nystagmus, and bleeding diathesis. A small number of patients will present with granulomatous colitis or fatal pulmonary fibrosis. At present, mutations in ten known genetic loci (HPS1-11) have been identified to be the genetic cause of HPS. In this study, we enrolled a consanguineous family who presented with typical HPS phenotypes, such as albinism, visual impairment, nystagmus, and bleeding diathesis. Whole-exome sequencing and Sanger sequencing were applied to explore the genetic lesions of the patient. A novel homozygous frameshift mutation (NM_032383.5, c.1231dupG/p.Aps411GlyfsTer32) of HPS3 was identified and cosegregated in the family members. Furthermore, real-time PCR confirmed that the mutation decreased the expression of HPS3, which has been identified as the disease-causing gene of HPS type 3. According to ACMG guidelines, the novel mutation, resulting in a premature stop codon at amino acid 442, is a pathogenic variant. In summary, we identified a novel mutation (NM_032383.5, c.1231dupG/p.Aps411GlyfsTer32) of HPS3 in a family with HPS. Our study expanded the variant spectrum of the HPS3 gene and contributed to genetic counseling and prenatal genetic diagnosis of the family.

Rumex roseus L. (R. roseus) is acknowledged as an aromatic plant. For its excellent biological properties, it was used as a traditional medicine. The aim of the present study is to evaluate the chemical components and their effect as the biological activities of Tunisian extracts of R. roseus. Consecutive extractions by cold maceration of the aerial part with solvents of increasing polarity (cyclohexane (CYH), dichloromethane (DCM), and methanol (MeOH)) were performed, and the different chemical groups (phenolics, flavonoids, tannins, anthocyanins, etc.) were identified. In addition, the volatile compounds of the obtained extracts were identified before and after derivatization. Moreover, their antioxidant and anticancer activities were evaluated. The analysis of HPLC-DAD revealed the identification of 18 components from organic extracts, among them are, for example, chlorogenic acid and shikonin, while GC-MS analysis allowed the detection of 34 volatile compounds. Some of those compounds were identified for the first time in plant extracts such as pyrazolo[3,4-d] pyrimidine-3,4(2H,5H)-dione (1); L-proline (16); 2-amino-3-hydroxybutanoic acid (19); L-(-)-arabitol (23); D-(-)-fructopyranose (25); and D-(+)-talopyranose (27). DPPH tests revealed that the most important antioxidant activity was found in the methanolic extract with 75.2% inhibition at 50 mg/L and that the highest cytotoxic activity against HCT-116 and MCF-7 was recorded in the dichloromethane extract with 62.1 and 80.0% inhibition at 50 mg/L, respectively. The biological activities were fully correlated with the chemical composition of the different extracts. So, we can suggest that R. roseus is a source of bioactive molecules that could be considered potential alternatives for use in dietary supplements for the prevention or treatment of diseases.

OBJECTIVE: To investigate the effects of S100A8 and S100A9 on proliferation in nasopharyngeal carcinoma cells and the regulatory effects of PI3K/Akt signaling pathway. METHODS: Nasopharyngeal carcinoma cells (CNE1) were cultured and randomly divided into three groups: control group, S100A8/S100A9 overexpression group, and siRNA S100A8/S100A9 group. CCK-8 method was used to detect the effect of S100A8 and S100A9 on the viability of nasopharyngeal carcinoma cells. The effects of S100A8 and S100A9 on the colony forming ability of nasopharyngeal carcinoma cells were detected by colony forming assay. The effects of S100A8 and S100A9 on the proliferation of nasopharyngeal carcinoma cells were detected by EdU staining. The mRNA levels of PI3K and Akt were detected by RT-PCR. The expression levels of PI3K and Akt in NPC cells were detected by Western blot. Wortmannin, an inhibitor of PI3K/Akt pathway, was used to inhibit the activation of PI3K/Akt pathway. RESULTS: Compared with the control group, the cell viability, the number of plate clones, the positive rate of EdU staining, and the mRNA and protein levels of PI3K and Akt were increased in the overexpression group. Compared with the control group, the cell viability, the number of plate clones, the positive rate of EdU staining, and the mRNA and protein levels of PI3K and Akt were decreased in the siRNA group. After inhibiting the activation of PI3K/Akt pathway, the viability of NPC cells in the overexpression group decreased significantly at 48 h and 72 h, while that in the siRNA group increased significantly. CONCLUSION: SiRNA S100A8 and S100A9 could inhibit the proliferation of nasopharyngeal carcinoma cells, and the underlying mechanism may be related to the inhibition of PI3K/Akt signaling pathway.

INTRODUCTION: This study was aimed at evaluating the association between vertical skeletal patterns, condylar height symmetry, and temporomandibular disorders in adults. METHODS: The study sample consisted of 200 patients (ages 18-30 years old) retrospectively recruited: 100 with temporomandibular disorders (TMD) and 100 without TMD (control), diagnosed by Diagnostic Criteria for the Temporomandibular Disorders (DC/TMD). For each subject, skeletal divergence was assessed on lateral cephalograms, and condylar height symmetry was evaluated by orthopantomography (Habets' method). RESULTS: Subjects with temporomandibular disorders showed a strong association with condylar asymmetry (p < 0.0001) and, for the skeletal pattern variables, hyperdivergence (p < 0.001). A correlation with the female sex was also found (p < 0.04), while there was no difference in terms of age in the 2 groups (p > 0.29). CONCLUSIONS: Although it does not imply a direct cause-and-effect relationship, the present study suggests condylar asymmetry and hyperdivergent skeletal pattern are more likely to be associated with a higher risk of temporomandibular disorder joint diseases in adult patients.

Oxygen tension is one of the most critical factors for mammalian embryo development and its survival. The HIF protein is an essential transcription factor that activated under hypoxic conditions. In this study, we evaluated the effect of dynamic oxygen conditions on the expression of embryonic genes and translocation of hypoxia-inducible factor-1α (HIF-1α) in cultured mouse blastocysts. Two-pronuclear (2PN) zygotes harvested from ICR mice were subjected to either high oxygen (HO; 20%), low oxygen (LO; 5%), or dynamic oxygen (DO; 5% to 2%) conditions. In the DO group, PN zygotes were cultured in 5% O2 from days 1 to 3 and then in 2% O2 till day 5 after hCG injection. On day 5, the percentage of blastocysts in the cultured embryos from each group was estimated, and the embryos were also subjected to immunocytochemical and gene expression analysis. We found that the percentage of blastocysts was similar among the experimental groups; however, the percentage of hatching blastocysts in the DO and LO groups was significantly higher than that in the HO group. The total cell number of blastocysts in the DO group was significantly higher than that of both the HO and LO groups. Further, gene expression analysis revealed that the expression of genes related to the embryonic development was significantly higher in the DO group than that in the HO and LO groups. Interestingly, HIF-1α mRNA expression did not significantly differ; however, HIF-1α protein translocation from the cytoplasm to the nucleus was significantly higher in the DO group than in the HO and LO groups. Our study suggests that dynamic oxygen concentrations increase the developmental capacity in mouse preimplantation embryos through activation of the potent transcription factor HIF-1α.

Problem-based learning is an experiential and student-centred learning method to practice important skills like querying, critical thinking, and collaboration through pair and group work. The study is aimed at comparing the effectiveness of problem-based learning (PBL) and traditional teaching (TT) methods in improving acquisition of radiographic interpretation skills among dental students. Clinical trials (randomized and nonrandomized) were conducted with the help of dental students studying oral radiology using PBL and TT methods and assessing radiographic interpretation skills, knowledge scores, and satisfaction level as outcomes. Articles published from PubMed/MEDLINE, DOAJ, Cochrane Central Register of Controlled Trials, and Web of Science were searched. The quality of the studies was evaluated using the Cochrane Collaboration Tool, the MINORS Checklist, and the Risk of Bias in Nonrandomized Studies of Interventions (ROBIN-I) tool. Meta-analysis was done using Review Manager 5.3. There were twenty-four articles for qualitative synthesis and 13 for meta-analysis. The cumulative mean difference was found to be 0.54 (0.18, 0.90), 4.15 (-0.35, 8.65), and -0.14 (-0.36, 0.08) for radiographic interpretation skills, knowledge scores, and satisfaction level, respectively, showing significant difference favouring PBL as compared to TT except for satisfaction level which favoured the TT group. To understand the long-term effectiveness of PBL over TT methods in oral radiology among dental students, well-designed long-term randomized controlled trials are needed.

This study is aimed at modeling biodigestion systems as a function of the most influencing parameters to generate two robust algorithms on the basis of the machine learning algorithms, including adaptive network-based fuzzy inference system (ANFIS) and least square support vector machine (LSSVM). The models are assessed utilizing multiple statistical analyses for the actual values and model outcomes. Results from the suggested models indicate their great capability of predicting biogas production from vegetable food, fruits, and wastes for a variety of ranges of input parameters. The values that are calculated for the mean relative error (MRE %) and mean squared error (MSE) were 29.318 and 0.0039 for ANFIS, and 2.951 and 0.0001 for LSSVM which shows that the latter model has a better ability to predict the target data. Finally, in order to have additional certainty, two analyses of outlier identification and sensitivity were performed on the input parameter data that proved the proposed model in this paper has higher reliability in assessing output values compared with the previous model.

BACKGROUND: Although vaccine rollout for COVID-19 has been effective in some countries, there is still an urgent need to reduce disease transmission and severity. We recently carried out a meta-analysis and found that pre- and in-hospital use of statins may improve COVID-19 mortality outcomes. Here, we provide an updated meta-analysis in an attempt to validate these results and increase the statistical power of these potentially important findings. METHODS: The meta-analysis investigated the effect of observational and randomized clinical studies on intensive care unit (ICU) admission, tracheal intubation, and death outcomes in COVID-19 cases involving statin treatment, by searching the scientific literature up to April 23, 2021. Statistical analysis and random effect modeling were performed to assess the combined effects of the updated and previous findings on the outcome measures. Findings. The updated literature search led to the identification of 23 additional studies on statin use in COVID-19 patients. Analysis of the combined studies (n = 47; 3,238,508 subjects) showed no significant effect of statin treatment on ICU admission and all-cause mortality but a significant reduction in tracheal intubation (OR = 0.73, 95% CI: 0.54-0.99, p = 0.04, n = 10 studies). The further analysis showed that death outcomes were significantly reduced in the patients who received statins during hospitalization (OR = 0.54, 95% CI: 0.50-0.58, p < 0.001, n = 7 studies), with no such effect of statin therapy before hospital admission (OR = 1.06, 95% CI = 0.82-1.37, p = 0.670, n = 29 studies). CONCLUSION: Taken together, this updated meta-analysis extends and confirms the findings of our previous study, suggesting that in-hospital statin use leads to significant reduction of all-cause mortality in COVID-19 cases. Considering these results, statin therapy during hospitalization, while indicated, should be recommended.

INTRODUCTION: The wide variety of methods for recording occlusal contacts and the contradictory data on the interpretation of the obtained markings provoked us to make a comparative laboratory study between different occlusal indicators. PURPOSE: Evaluation of a qualitative and quantitative method for registration of occlusal contacts in static occlusion in laboratory conditions. MATERIALS AND METHODS: In completion of the objective, we designed an apparatus for registration of the occlusal contacts (AROC) in static occlusion which is used, corresponding to the MIP in clinical conditions. The occlusal indicators that were included in the study were articulating paper 100 μ, articulating foil 12 μ, and T-Scan Novus system with a sensor thickness of 100 μ. The collected primary statistical information was entered and processed with the statistical package SPSS Statistics 19.0, and the graphs were prepared using Microsoft Office 2019. We performed descriptive statistical analysis in this study. Comparisons were performed using one-way analysis of variance (ANOVA), Student's t-test, and Pearson coefficient method. For a significance level, p < 0.05 was chosen. Result and Discussion. With quality occlusal indicators, it is possible only to visually determine the size, number, and intensity of the marked contacts. After the statistical processing of the obtained data on the number of registered contacts, a significant difference is found in the number of contacts of certain teeth (18, 24, 25, 28, 38, 35, 34, 33, 44, 45, and 48) registered with articulating paper and articulating foil. The maximum force that is reported during the study with the T-Scan system is 93.72% and the forces in the right half of the dentition are 51.7% and in the left 48.9%. To visualize the location of the registered occlusal contacts with the system, it is intraoral to use a quality indicator and we recommend the use of articulating foil. CONCLUSION: Based on findings from the current in vitro simulation, we can conclude that the type of occlusal indicator influences the registration of contacts, and therefore, we propose as a method of choice to achieve a balanced occlusion in clinical practice to combine the use of one conventional and one quantitative method.

The study is aimed at observing the influence of microribonucleic acid- (miRNA-) 30a-50p on the pulmonary fibrosis in mice with Streptococcus pneumoniae infection through the regulation of autophagy by Beclin-1. Specific pathogen-free mice were instilled with Streptococcus pneumoniae through the trachea to establish the pulmonary fibrosis model. Then, they were divided into the miRNA-30a-50p mimics group (mimics group, n = 10) and miRNA-30a-5p inhibitors group (inhibitors group, n = 10), with the control group (n = 10) also set. Pulmonary tissue wet weight/dry weight (W/D) was detected. The content of tumor necrosis factor-α (TNF-α), interleukin- (IL-) 6, and myeloperoxidase (MPO) was determined using enzyme-linked immunosorbent assay (ELISA). Besides, the changes in the pulmonary function index dynamic lung compliance (Cdyn), plateau pressure (Pplat), and peak airway pressure (Ppeak) were monitored, and the gene and protein expression levels were measured via quantitative PCR (qPCR) and Western blotting. The expression level of miRNA-30a-5p was substantially raised in the mimics group (p < 0.05), but extremely low in the inhibitors group (p < 0.05). The mimics group had obviously raised levels of serum aminotransferase (AST), glutamic-pyruvic transaminase (GPT), alkaline phosphatase (ALP), and pulmonary tissue W/D (p < 0.05). Additionally, the expression levels of TNF-α, IL-6, and MPO were notably elevated in the mimics group, while their expression levels showed the opposite conditions in the inhibitors group (p < 0.05). According to the HE staining results, the inhibitors group had arranged orderly cells, while the mimics group exhibited lung injury, pulmonary edema, severe inflammatory response, and alveolar congestion. In the inhibitors group, Cdyn was remarkably elevated, but Pplat and Ppeak declined considerably (p < 0.05). Besides, the inhibitors group exhibited elevated messenger RNA (mRNA) levels of Beclin-1 and LC3, lowered mRNA levels of α-SMA and p62, a raised protein level of Beclin-1, and a markedly decreased protein level of p62 (p < 0.05). Silencing miRNA-30a-5p expression can promote the expression of Beclin-1 to accelerate the occurrence of autophagy, thereby treating pulmonary fibrosis in mice with Streptococcus pneumoniae infection.

Hepatocellular carcinoma (HCC) is one of the most common and lethal malignancies worldwide. Although there have been extensive studies on the molecular mechanisms of its carcinogenesis, FDA-approved drugs for HCC are rare. Side effects, development time, and cost of these drugs are the major bottlenecks, which can be partially overcome by drug repositioning. In this study, we developed a computational framework to study the mechanisms of HCC carcinogenesis, in which drug perturbation-induced gene expression signatures were utilized for repositioning of potential drugs. Specifically, we first performed differential expression analysis and coexpression network module analysis on the HCC dataset from The Cancer Genome Atlas database. Differential gene expression analysis identified 1,337 differentially expressed genes between HCC and adjacent normal tissues, which were significantly enriched in functions related to various pathways, including α-adrenergic receptor activity pathway and epinephrine binding pathway. Weighted gene correlation network analysis (WGCNA) suggested that the number of coexpression modules was higher in HCC tissues than in normal tissues. Finally, by correlating differentially expressed genes with drug perturbation-related signatures, we prioritized a few potential drugs, including nutlin and eribulin, for the treatment of hepatocellular carcinoma. The drugs have been reported by a few experimental studies to be effective in killing cancer cells.

OBJECTIVES: Undernutrition early in life may increase the incidence of adverse effects on adult health. The relations between undernutrition and obesity parameters (body mass index (BMI) and WC (waist circle)) and hypertension were often contradictory. Our study is aimed at identifying the combined effects of famine exposure and obesity parameters on hypertension in middle-aged and older Chinese. DESIGN: A population-based cross-sectional study. Setting. Data were selected from the China Health and Retirement Longitudinal Study Wave2011 (CHARLS Wave2011). Participants. The sample included 12945 individuals aged 45 to 96. Main Outcome Measurements. The study analyzed data from 12945 middle-aged and older Chinese selected from CHARLS Wave2011. Differences between baseline characteristics and famine exposure/BMI levels/WC levels were evaluated using the t-, Chi-square- (χ 2-), and F-test. Then, the difference in the prevalence of hypertension between baseline characteristics was estimated by the t- and χ 2-test. Finally, multivariable-adjusted logistic regression models were used to explore the associations of famine exposure and obesity parameters with odds of prevalence of hypertension. RESULTS: Among the 12945 participants, 1548 (11.96%) participants had been exposed to the Chinese famine during the fetal group, whereas 5101 (39.41%) participants and 4362 (33.70%) participants had been exposed to the famine during childhood and adolescence/adult group, respectively. Regarding the participants with BMI levels, 3746 (28.94%) were overweight, and 1465 (11.32%) were obese, whereas 5345 (41.29%) of the participants with WC levels were obese, respectively. Furthermore, 1920 (31.17%) had hypertension in males and 2233 (32.91%) in females. In multivariable-adjusted models, famine exposure and obesity parameters were related with prevalence of hypertension independently in total populations ((1) model threec, famine exposure with prevalence of hypertension: the fatal-exposed vs. no-exposed group (OR1.27; 95% CI 1.08, 1.49); childhood-exposed vs. no-exposed group (OR1.64; 95% CI 1.44, 1.87); the adolescence/adult-exposed vs. no-exposed group (OR3.06; 95% CI 2.68, 3.50); P for trend < 0.001; (2) model threee, famine exposure with prevalence of hypertension: the fatal-exposed vs. no-exposed group (OR1.25; 95% CI 1.06, 1.47); childhood-exposed vs. no-exposed group (OR1.52; 95% CI 1.34, 1.73); the adolescence/adult-exposed vs. no-exposed group (OR2.66; 95% CI 2.33, 3.03); P for trend < 0.001; (3) model threeg, BMI levels with prevalence of hypertension: overweight vs. normal (OR1.75; 95% CI 1.60, 1.91); obesity vs. normal (OR2.79; 95% CI 2.48, 3.15); P for trend < 0.001; (4) WC levels with prevalence of hypertension: overweight vs. normal (OR1.42; 95% CI 1.36, 1.48)). When stratified by sex, results in both males and females were mostly similar to those in the total population. In general, interaction analysis in the multivariable-adjusted model, compared with the combination of normal BMI/WC levels and no-exposed famine group, all groups trended towards higher odds of prevalence of hypertension (the greatest increase in odds, adolescence/adult-exposed group with obesity in BMI levels: (OR8.13; 95% CI 6.18, 10.71); adolescence/adult-exposed group with obesity in WC levels: (OR6.36; 95% CI 5.22, 7.75); P for interaction < 0.001). When stratified by sex, the results in both males and females were also similar to those in the total population. CONCLUSION: Our data support a strongly positive combined effect of famine exposure and obesity parameters on hypertension in middle-aged and elderly Chinese.

Trogocytosis is a general biological process that involves one cell physically taking small parts of the membrane and other components from another cell. In trogocytosis, one cell seems to take little "bites" from another cell resulting in multiple outcomes from these cell-cell interactions. Trogocytosis was first described in protozoan parasites, which by taking pieces of host cells, kill them and cause tissue damage. Now, it is known that this process is also performed by cells of the immune system with important consequences such as cell communication and activation, elimination of microbial pathogens, and even control of cancer cells. More recently, trogocytosis has also been reported to occur in cells of the central nervous system and in various cells during development. Some of the molecules involved in phagocytosis also participate in trogocytosis. However, the molecular mechanisms that regulate trogocytosis are still a mystery. Elucidating these mechanisms is becoming a research area of much interest. For example, why neutrophils can engage trogocytosis to kill Trichomonas vaginalis parasites, but neutrophils use phagocytosis to eliminate already death parasites? Thus, trogocytosis is a significant process in normal physiology that multiple cells from different organisms use in various scenarios of health and disease. In this review, we present the basic principles known on the process of trogocytosis and discuss the importance in this process to host-pathogen interactions and to normal functions in the immune and nervous systems.

PURPOSE: Osteosarcoma is the most common primary and highly invasive bone tumor in children and adolescents. The purpose of this study is to construct a multi-gene expression feature related to autophagy, which can be used to predict the prognosis of patients with osteosarcoma. Materials and methods. The clinical and gene expression data of patients with osteosarcoma were obtained from the target database. Enrichment analysis of autophagy-related genes related to overall survival (OS-related ARGs) screened by univariate Cox regression was used to determine OS-related ARGs function and signal pathway. In addition, the selected OS-related ARGs were incorporated into multivariate Cox regression to construct prognostic signature for the overall survival (OS) of osteosarcoma. Use the dataset obtained from the GEO database to verify the signature. Besides, gene set enrichment analysis (GSEA) were applied to further elucidate the molecular mechanisms. Finally, the nomogram is established by combining the risk signature with the clinical characteristics. RESULTS: Our study eventually included 85 patients. Survival analysis showed that patients with low riskScore had better OS. In addition, 16 genes were included in OS-related ARGs. We also generate a prognosis signature based on two OS-related ARGs. The signature can significantly divide patients into low-risk groups and high-risk groups, and has been verified in the data set of GEO. Subsequently, the riskScore, primary tumor site and metastasis status were identified as independent prognostic factors for OS and a nomogram were generated. The C-index of nomogram is 0.789 (95% CI: 0.703~0.875), ROC curve and calibration chart shows that nomogram has a good consistency between prediction and observation of patients. CONCLUSIONS: ARGs was related to the prognosis of osteosarcoma and can be used as a biomarker of prognosis in patients with osteosarcoma. Nomogram can be used to predict OS of patients and improve treatment strategies.

Lignocellulosic waste is the most abundant biorenewable biomass on earth, and its hydrolysis releases highly valued reducing sugars. However, the presence of lignin in the biopolymeric structure makes it highly resistant to solubilization thereby hindering the hydrolysis of cellulose and hemicellulose. Microorganisms are known for their potential complex enzymes that play a dominant role in lignocellulose conversion. Therefore, the current study was designed to isolate and screen potential microorganisms for their selective delignification ability for the pretreatment of lignocellulosic biomass. An extensive isolation and screening procedure yielded 36 desired isolates (22 bacteria, 7 basidiomycete fungi, and 7 filamentous fungi). Submerged cultivation of these desired microorganisms revealed 4 bacteria and 10 fungi with potent lignocellulolytic enzyme activities. The potent isolates were identified as Pleurotus, Trichoderma, Talaromyces, Bacillus, and Chryseobacterium spp. confirmed by morphological and molecular identification. The efficiency of these strains was determined through enzyme activities, and the degraded substrates were analyzed through scanning electron microscopy (SEM) and X-ray diffraction (XRD). Among all isolated microbes, Pleurotus spp. were found to have high laccase activity. The cellulose-decomposing and selective delignification strains were subjected to solid-state fermentation (SSF). SSF of field waste corn stalks as a single-carbon source provides Pleurotus spp. better condition for the secretion of ligninolytic enzymes. These isolated ligninolytic enzymes producing microorganisms may be used for the effective pretreatment of lignocellulosic agricultural wastes for the production of high value-added natural products by fermentation.

BACKGROUND: To date, hemodialysis (HD) is the most common therapy for chronic kidney disease (CKD) patients. However, it causes different complications such as sleep disorders. Sleep regulation is connected to vitamin D; hence, its deficiency might influence the quality and duration of sleep. This study is aimed at evaluating the correlation of sleep quality and vitamin D levels in 80 HD patients. METHODS: This cross-sectional study was performed on 80 hemodialysis patients admitted to 29 Bahman hospitals in Tabriz, Iran. Before beginning of dialysis, serum 25 (OH) D levels were assessed among patients and the sleep patterns and sleep quality of patients were accurately calculated by the Pittsburgh sleep quality index (PSQI) standard questionnaire. RESULTS: Our results showed that 22 HD patients (27.5%) had severe sleep disorders. In addition, it was found that serum levels of vitamin D had significant correlation with sleep quality (r = -0.341, p = 0.002) in general, even after adjusting confounding factors such as calcium (Ca), phosphate (P), and parathyroid hormone (PTH) level. In poor sleepers (PSQI ≤ 5), a negative correlation was observed between the levels of vitamin D and PSQI score (r = -0.397, p = 0.004). PSQI scores in the normal range of PTH (r = -0.377, p = 0.006) and in >600 pg/ml of PTH (r = -0.675, p = 0.011) had a correlation with vitamin D levels. The level of vitamin D was the single independent predictor of sleep efficiency (β coefficient = -0.386, p = 0.001). CONCLUSION: The present project reported that the positive effect of vitamin D is associated with sleep disorder in HD patients. In future studies, normal levels of Ca and P should be considered along with normal vitamin D levels among the included patients.

Breast cancer is one of the most common malignancies. Pathological image processing of breast has become an important means for early diagnosis of breast cancer. Using medical image processing to assist doctors to detect potential breast cancer as early as possible has always been a hot topic in the field of medical image diagnosis. In this paper, a breast cancer recognition method based on image processing is systematically expounded from four aspects: breast cancer detection, image segmentation, image registration, and image fusion. The achievements and application scope of supervised learning, unsupervised learning, deep learning, CNN, and so on in breast cancer examination are expounded. The prospect of unsupervised learning and transfer learning for breast cancer diagnosis is prospected. Finally, the privacy protection of breast cancer patients is put forward.

BACKGROUND: Human papillomavirus (HPV) causes over 99% of all cervical cancer globally. In 2019, it was responsible for 3286 deaths in Kenya. Data on the epidemiological distribution of HPV genotypes by cervical dysplasia and HIV-infected women which is important in designing prevention strategy monitoring treatment and management of cervical cancer is lacking in Eastern Kenya. OBJECTIVE: To determine HPV genotype prevalence and their association with cervical dysplasia among HIV-infected (cases) and noninfected (control) women aged 18-48 years seeking reproductive healthcare. METHODS: A cervical broom was softly rotated 360 degrees five times to exfoliate cells from the region of the transformation zone, squamocolumnar junction, and endocervical canal for HPV genotyping. Social-demographic and risk factors responsible for HPV acquisition were collected using a questionnaire. Laboratory outcome and questionnaire data statistical relationships were computed using Pearson chi-square test. RESULTS: 317 women (cases: 161 (50.8%), control 156 (49.2%), mean age: 34.3,SD ± 10.4, range 18-46 years) were recruited from Embu (85/317 (26.8%)), Isiolo (64/317 (20.2%)), Kirinyaga (56/317 (17.7%)), Meru (81/317 (25.6%)), and Tharaka-Nithi (31/317 (9.8%)). The frequency HPV genotypes detected by cervical dysplasia were CIN1 (cases: HPV81 (12/317 (3.8%)), HPV11 (2/317 (0.6%)); control: HPV53 and 66 coinfection (1/317 (0.3%)), CIN2 (cases: HPV11, HPV16, HPV66 ((1/317 (0.3%) each), HPV81 (6/317 (1.9%)), and single case (1/317 (0.3%)) of HPV11 and 66, HPV81 and 44, HPV81 and 88, HPV9 and 53, and HPV16 and 58 coinfection; control: HPV81 (2/317 (0.6%)) and invasive cervical cancer (cases: HPV16 (1/317 (0.3%)) and HPV81 (3/317 (0.9%)); control: HPV16 and 66 (1/317 (0.3%))). CONCLUSIONS: There was a higher frequency of both high-risk and low-risk HPV genotypes associated with cervical dysplasia among HIV-infected than HIV-uninfected women seeking reproductive health care. This study provides epidemiological data on the existence of nonvaccine HPV types associated with cervical dysplasia in the region.

Lonicerae japonicae flos (LJF) is widely used for the treatment of inflammation-related diseases in traditional Chinese medicine (TCM). To clarify the anti-inflammatory mechanism of LJF, 29 compounds with high content in LJF were selected for network pharmacology. Then, a comprehensive network pharmacology strategy was implemented, which involved compound-inflammation-target construction, protein-protein interaction (PPI) network analysis, and enrichment analysis. Finally, molecular docking and in vitro experiments were performed to verify the anti-inflammatory activity and targets of the key compound. As a result, 279 inflammation-associated proteins were identified, which are mainly involved in the AGE/RAGE signaling pathway in diabetic complications, the HIF-1 signaling pathway, the PI3K-AKT signaling pathway, and EGFR tyrosine kinase inhibitor resistance. A total of 12 compounds were linked to more than 35 targets, including apigenin, kaempferol, quercetin, luteolin, and ferulic acid. The results of molecular docking showed that AKT has the most binding activity, exhibiting certain binding activity with 10 compounds, including vanillic acid, protocatechuic acid, secologanic acid, quercetin, and luteolin; the results of qRT-PCR and WB confirmed that two key compounds, secologanic acid and luteolin, could significantly decrease the secretion of TNF-α and the AKT expression of RAW264.7 murine macrophages stimulated by LPS (lipopolysaccharide). These results demonstrate that the comprehensive strategy can serve as a universal method to illustrate the anti-inflammatory mechanisms of traditional Chinese medicine by identifying the pathways or targets.

OBJECTIVE: This study is aimed at analyzing the relationship between leptin (LEP) signaling pathway and type 2 diabetes mellitus (T2DM) and at providing support for molecular genetic research on the pathogenesis of T2DM in Chinese Han population. METHODS: A case-control study was designed, including 1092 cases with T2DM and 1092 healthy controls of Chinese Han origin recruited from ten hospitals in Guangdong Province, Southern China. Twenty-three single nucleotide polymorphisms (SNPs) of 15 genes in LEP signaling pathway were genotyped by SNPscan™ kit. The Pearson chi-square test, Cochran-Armitage trend test, MAX3, and logistic regression were applied to analyze the association between single nucleotide polymorphism (SNP) and T2DM; unconditional logistic regression was used to analyze haplotype in LD block; and SNP set analysis based on logistic kernel machine regression was used to analyze pathway. All statistical analysis was performed by SPSS25.0, R2.14, Haploview4.2, SNPStats, and other statistical software packages. RESULTS: In association analysis based on SNP, rs2167270 had statistical significance both in the adjusted and unadjusted covariate dominant model and in the unadjusted covariate overdominant model while it had no significant difference in the adjusted covariate overdominant model. Compared to GG genotype, rs2167270 of AG genotype had statistical significance in both the adjusted and unadjusted covariate codominant models. And rs16147 had statistical significance in robust test, stealth model and overdominant model, and adjusting and unadjusting covariate. This study found linkage disequilibrium existed between rs2167270 and rs4731426 of LEP, rs10889502 and rs17127107 of JAK1, rs2970847 and rs6821591 of PPARGC1A, rs249429 and rs3805486 of PRKAA1, rs1342382 and rs6588640 of PRKAA2, rs3766522 and rs6937 of PRKAB2, rs2970847 and rs6821591 of PRKAG2, and rs6436094 and rs645163 of PRKAG3. There was no positive finding with statistical significance from the unconditional logistic regression of the mentioned genes' haplotype of LD block. CONCLUSIONS: LEP signaling pathway association with T2DM remained to be confirmed in Chinese Han population, although rs2167270 and rs16147 were significantly associated with T2DM.

Asthma is a T helper 2 (Th2) cell-associated chronic inflammatory diseases characterized with airway obstruction, increased mucus production, and eosinophil infiltration. Conventional medications for asthma treatment cannot fully control the symptoms, and potential side effects are also the concerns. Thus, complement or alternative medicine (CAM) became a new option for asthma management. Ding Chuan Tang (DCT) is a traditional Chinese herbal decoction applied mainly for patients with coughing, wheezing, chest tightness, and asthma. Previously, DCT has been proved to improve children airway hyperresponsiveness (AHR) in a randomized and double-blind clinical trial. However, the mechanisms of how DCT alleviates AHR remain unclear. Since asthmatic features such as eosinophil infiltration, IgE production, and mucus accumulation are relative with Th2 responses, we hypothesized that DCT may attenuate asthma symptoms through regulating Th2 cells. Ovalbumin (OVA) was used as a stimulant to sensitize BALB/c mice to establish an asthmatic model. AHR was detected one day before sacrifice. BALF and serum were collected for immune cell counting and antibody analysis. Splenocytes were cultured with OVA in order to determine Th2 cytokine production. Lung tissues were collected for histological and gene expression analyses. Our data reveal that DCT can attenuate AHR and eosinophil accumulation in the 30-day sensitization asthmatic model. Histological results demonstrated that DCT can reduce cell infiltration and mucus production in peribronchial and perivascular site. In OVA-stimulated splenocyte cultures, a significant reduction of IL-5 and IL-13 in DCT-treated mice suggests that DCT may alleviate Th2 responses. In conclusion, the current study demonstrates that DCT has the potential to suppress allergic responses through the reduction of mucus production, eosinophil infiltration, and Th2 activity in asthma.

BACKGROUND: Pancreatic cancer (PC) is one of the most common cancers worldwide, with high mortality. The UGT1A gene family plays important roles in pharmacology and toxicology, contributing to interindividual differences in drug disposition. However, mRNA expression and prognostic value of the UGT1A gene family in PC have not been identified. METHODS: Oncomine, GEPIA2, DAVID 6.8, Metascape, Kaplan-Meier plotter, cBioPortal, GeneMANIA, TRRUST v2, TIMER, and R software were used in our study. RESULTS: The transcriptional levels of UGT1A1/3/6/8/9/10 in PC tissues were significantly higher than those in normal tissues. These results were further validated using five pairs of PC tumor tissues and adjacent nontumor tissues. A significant correlation was found between the expression of UGT1A1/6/10 and the pathological stage of PC. PC patients with lower transcriptional levels of UGT1A1/4/5/6/10 were associated with a better prognosis. The differentially expressed UGT1A gene family functions were primarily related to the glucuronidation pathway, cytokine-cytokine receptor interactions, and the ILK signaling pathway. Our data suggest that HNF1A, AHR, and CDX2 are key transcription factors for the UGT1A gene family. Furthermore, the expression levels of UGT1A1/3/8/9/10 were positively correlated with the activities of tumor-infiltrating immune cells, especially B cells. The expression levels of UGT1A6/9 were negatively correlated with macrophage infiltration levels. CONCLUSIONS: These results suggest that the UGT1A gene family could serve as a potential prognostic biomarker and target for PC. However, future studies are required to validate our findings and promote the clinical utility of the UGT1A gene family in PC.

BACKGROUND: Circulating tumor cells (CTCs) have been regarded as an independent prognostic marker for metastatic castration-resistant prostate cancer (mCRPC). Its prognostic value, however, in nonmetastatic prostate cancer (NMPC) is still unclear. PURPOSE: To elucidate whether CTCs can predict the biochemical recurrence (BCR) in NMPC patients following radical prostatectomy (RP) or radiotherapy (RT). METHODS: PubMed, Cochrane Database, and Embase and the references in relevant studies were systematically searched. Studies that investigated the correlation of CTCs and BCR in NMPC patients after RP or RT were identified and reviewed. Overall odds ratio (OR) of BCR in such patients with/without CTCs was pooled. We also calculated and pooled overall prevalence of BCR in such CTC-positive patients. RESULTS: In total, 12 studies comprising 1917 participants were eligible for the meta-analysis and showed that the presence of secondary circulating tumor cells (SCTCs) is associated with a higher BCR rate of 59% (95% CI: 22%-88%) in patients with NMPC after RP or RT (OR = 6.12; 95% CI: 2.22-16.85; P < 0.001). However, regardless of the presence of primary circulating tumor cells (PCTCs), it has not been shown to be associated with higher BCR. CONCLUSIONS: Our research demonstrated that SCTC-positive patients are associated with higher BCR compared to SCTC-negative patients in NMPC. Therefore, it is recommended that NMPC patients undergo CTC surveillance intensively after RP or RT.

The main aim of this study was to develop a set of functions that can analyze the genomic data with less time consumption and memory. Epi-gene is presented as a solution to large sequence file handling and computational time problems. It uses less time and less programming skills in order to work with a large number of genomes. In the current study, some features of the Epi-gene R-package were described and illustrated by using a dataset of the 14 Aeromonas hydrophila genomes. The joining, relabeling, and conversion functions were also included in this package to handle the FASTA formatted sequences. To calculate the subsets of core genes, accessory genes, and unique genes, various Epi-gene functions have been used. Heat maps and phylogenetic genome trees were also constructed. This whole procedure was completed in less than 30 minutes. This package can only work on Windows operating systems. Different functions from other packages such as dplyr and ggtree were also used that were available in R computing environment.

In our study, the value of cholesterol biosynthesis is related to clinical analysis in 32 cancer forms in the GSEA database facility. We have a mutation between 25 CBRGs. In The Cancer Genome Atlas database, clear cell renal cell carcinoma (ccRCC, n = 539) was upregulated or downregulated in 22 out of 25 cases (n = 72) compared with normal kidney tissue. Then, using LASSO regression analysis, the survival model that is based on nine risk-related CBRGs (CYP51A1, HMGCR, HMGCS1, IDI1, FDFT1, SQLE, ACAT2, FDPS, and NSDHL) is established. ROC curves confirmed the good omen of the new survival mode, and the area under the curve is 0.72 (5 years) and 0.709 (10 years). High SQLE and ACAT2 expression and low NSDHL, FDPS, CYP51A1, FDFT1, HMGCS1, HMGCR, and IDI1 expression were closely related to patients with high-risk renal clear cell carcinoma. Two types of Cox regression, uni- and multivariate, were used to determine risk scores, age, staging, and grade as independent risk factors for prognosis in patients with clear cell renal cell carcinoma. The results showed the prediction model established by 9 selected CBRGs could predict the prognosis more accurately.

Several decades of improving dairy cattle towards unilateral utilization of dairy cattle led to enormous progress in the field of milk yield; however, it resulted in a number of unfavorable features, such as reproductive disorders, increased calf mortality, and reduced health. Most cases of embryo loss and/or lost pregnancies occur during the first four to five weeks of gestation; accurate detection for pregnancy during this period is likely to contribute to an improvement in gestation rates. A specific protein, interferon-tau (IFNT), stimulates interferon-stimulated genes (ISGs), and their expression increases during gestation within 21 days after insemination. In bovines, the early conceptus undergoes a phase of rapid growth and elongation before implantation, the latter occurring 2-3 weeks after fertilization. IFNT acts mainly in the endometrium of the luminal epithelium. It is a new type I interferon that regulates several genes encoding uterine-derived factors. They are crucial in the processes of preparing the uterus for placenta attachment, modifying the uterine immune system, and regulating early fetal development. Because IFNT is expressed and induces ISGs in the endometrium during pregnancy recognition, it was reasoned that surrogate markers for pregnancy or IFNT might be present in the blood and provide an indicator of pregnancy status in cattle.

Accurate recognition of progressive mild cognitive impairment (MCI) is helpful to reduce the risk of developing Alzheimer's disease (AD). However, it is still challenging to extract effective biomarkers from multivariate brain structural magnetic resonance imaging (MRI) features to accurately differentiate the progressive MCI from stable MCI. We develop novel biomarkers by combining subspace learning methods with the information of AD as well as normal control (NC) subjects for the prediction of MCI conversion using multivariate structural MRI data. Specifically, we first learn two projection matrices to map multivariate structural MRI data into a common label subspace for AD and NC subjects, where the original data structure and the one-to-one correspondence between multiple variables are kept as much as possible. Afterwards, the multivariate structural MRI features of MCI subjects are mapped into a common subspace according to the projection matrices. We then perform the self-weighted operation and weighted fusion on the features in common subspace to extract the novel biomarkers for MCI subjects. The proposed biomarkers are tested on Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. Experimental results indicate that our proposed biomarkers outperform the competing biomarkers on the discrimination between progressive MCI and stable MCI. And the improvement from the proposed biomarkers is not limited to a particular classifier. Moreover, the results also confirm that the information of AD and NC subjects is conducive to predicting conversion from MCI to AD. In conclusion, we find a good representation of brain features from high-dimensional MRI data, which exhibits promising performance for predicting conversion from MCI to AD.

The paper presents the results of studying the immunological parameters of 369 people who were practically healthy at the time of the survey, 298 women and 71 men, of which 216 people are living in the European North of the Russian Federation (173 women and 43 men) and 153 are residents of the Arctic (125 women and 28 men). The study was carried out in the morning (08:00-10:00 am). The study included the determination of the aggregation of erythrocytes, platelets, neutrophilic granulocytes, lymphocytes, hemogram study, hematological analysis, enzyme immunoassay, and flow cytometry. Statistical processing of the obtained data was carried out using the Statistica 7.0 software package (StatSoft, USA). It was found that the activity of aggregation of cells of peripheral venous blood in Arctic residents is 1.5-1.7 times higher than that in people living in more favourable climatic conditions. The frequency of registration of aggregation of erythrocytes and platelets is actually 2 times higher than the aggregation of leukocytes. Aggregation of erythrocytes is associated with an increase in the concentrations of transferrin and receptors for this transport protein. The frequency of detection of platelet aggregation is accompanied by an increase in transferrin concentrations; in cases of aggregation of nonnuclear blood cells, the content of NO2 in the blood serum is increased. Aggregation of neutrophilic granulocytes and lymphocytes is associated with an increase in the content of free adhesion molecules. Aggregation of erythrocytes and platelets is in evidence when it is necessary to trigger reactions of changes in the hemodynamics of microcirculation to increase the efficiency of oxygen and trophic supply of tissues. The adhesion of leukocytes to the endothelium determines the secretion of biologically active substances that contribute to a change in microcirculation and an increase in the migration of leukocytes into tissues for the implementation of phagocytic and cytolytic functions.

BACKGROUND: Non-small-cell lung cancer (NSCLC) is a prevalent malignancy with high mortality and poor prognosis. The radiotherapy is one of the most common treatments of NSCLC, and the radiotherapy sensitivity of patients could affect the individual prognosis of NSCLC. However, the prognostic signatures related to radiotherapy response still remain limited. Here, we explored the radiosensitivity-associated genes and constructed the prognostically predictive model of NSCLC cases. METHODS: The NSCLC samples with radiotherapy records were obtained from The Cancer Genome Atlas database, and the mRNA expression profiles of NSCLC patients from the GSE30219 and GSE31210 datasets were obtained from the Gene Expression Omnibus database. The Weighted Gene Coexpression Network Analysis (WGCNA), univariate, least absolute shrinkage and selection operator (LASSO), multivariate Cox regression analysis, and nomogram were conducted to identify and validate the radiotherapy sensitivity-related signature. RESULTS: WGCNA revealed that 365 genes were significantly correlated with radiotherapy response. LASSO Cox regression analysis identified 8 genes, including FOLR3, SLC6A11, ALPP, IGFN1, KCNJ12, RPS4XP22, HIST1H2BH, and BLACAT1. The overall survival (OS) of the low-risk group was better than that of the high-risk group separated by the Risk Score based on these 8 genes for the NSCLC patients. Furthermore, the immune infiltration analysis showed that monocytes and activated memory CD4 T cells had different relative proportions in the low-risk group compared with the high-risk group. The Risk Score was correlated with immune checkpoints, including CTLA4, PDL1, LAG3, and TIGIT. CONCLUSION: We identified 365 genes potentially correlated with the radiotherapy response of NSCLC patients. The Risk Score model based on the identified 8 genes can predict the prognosis of NSCLC patients.

Hybrid locking pancarpal arthrodesis plates were designed with either a round (RH) or an oval (OH) radiocarpal hole, the latter allowing varied screw positioning. Due to concerns about potential decreased structural properties of the OH design, our aim was to compare the mechanical behavior of the contrasting plates using combined finite element analysis (FEA) and mechanical testing. Pancarpal arthrodesis plates with RH or OH design were assigned to three fixation techniques (n = 6), prebent at 20°, and fixed to canine forelimb models with simulated radius and radiocarpal and 3rd metacarpal bones. OH plates were instrumented with a radiocarpal screw inserted either most proximal (OH-P) or most distal (OH-D). Specimens were axially loaded to 300 N over 10 ramped cycles at 0.5 Hz. Plate strains were measured with strain gauges placed at areas of highest deformations as predicted by FEA under identical loading conditions. FEA predicted the highest strains (μm/m) adjacent to the radiocarpal hole (2,500 [RH], 2,900 [OH-P/OH-D]) and plate bending point (2,250 [RH], 1,900 [OH-P/OH-D]). Experimentally, peak radiocarpal hole strains were not influenced by the OH screw position (3,329 ± 443 [OH-P], 3,222 ± 467 [OH-D]; P = 0.550) but were significantly higher compared to the RH design (2,123 ± 154; P < 0.001). Peak strains at the bending point were significantly lower for OH-P (1,792 ± 174) and OH-D (1,806 ± 194) versus RH configurations (2,158 ± 114) (P ≤ 0.006). OH plates demonstrated highest peak strains next to the radiocarpal hole and were associated with more heterogenous plate strain distribution. Structural weakening associated with radiocarpal OH plate design could result in decreased fixation strength and increased risk of plate fatigue failure.

Nontyphoidal Salmonella (NTS) is one of the major causes of bacterial foodborne infection. It is mainly manifested by self-limiting gastroenteritis in healthy individuals but can also cause severe complications including blood stream infection and mortality. The emergence of multidrug-resistant strains of Salmonella is becoming a global public health concern. This study is aimed at estimating the prevalence of Salmonella, identifying serotypes involved, and investigating antimicrobial susceptibility of the isolates among diarrheic patients attending private hospitals in Addis Ababa. We collected a total of 298 stool samples from diarrheic patients attending five private hospitals in Addis Ababa and isolated Salmonella according to standard microbiological techniques; the isolates were serotyped using slide agglutination and microplate agglutination techniques. Antimicrobial susceptibility test of the isolates was carried out using Kirby-Bauer disc diffusion assay according to Clinical Laboratory Standards Institute guidelines. Fourteen stool samples (4.7%) were positive for Salmonella, and Salmonella Kiambu was the most dominant serovar (n = 7, 50%) followed by S. Saintpaul (n = 4, 28.6%) and S. Haifa (n = 2, 14.3%). Three (21.4%) of the isolates were resistant to sulfisoxazole and tetracycline each and 2 (14.3%) to ampicillin. Resistance to two antimicrobials was detected only in 2 (14.3%) of the isolates, and none of the isolates were resistant to more than two antimicrobials. In conclusion, the current study showed low prevalence of NTS in diarrheic patients attending private hospitals in Addis Ababa. Although multidrug resistance to several antimicrobials was not detected in the isolates, prudent use of antimicrobials is recommended to guaranty the long-term use of the available antimicrobials.

OBJECTIVE: Knowledge regarding the prevalence and risk factors of hepatitis C virus (HCV) infection among pregnant women can give clue to health care providers regarding the appropriate management of HCV infection. Therefore, this study was conducted to determine the prevalence, genotypic pattern, and risk factors of HCV infection among pregnant women in the northern shores of the Persian Gulf, south of Iran. METHODS: From January 2018 to June 2019, serum samples were obtained from 1425 pregnant women, ages ranging from 14 to 46 years (28.1 ± 5.99). Serum samples were tested for detection of anti-HCV antibodies using an enzyme-linked immunosorbent assay (ELISA) (HCV Ab ELISA kit, Dia.Pro, Milan, Italy). Following the extraction of nucleic acid, the molecular evaluation of HCV infection was performed by seminested reverse transcriptase-polymerase chain reaction assay (RT-PCR), targeting the 5' untranslated region (5'UTR) and core of HCV genome and sequencing. RESULTS: Of the 1425 pregnant women, 19 women (1.33%, 95% CI: 0.85%-2.07%) were positive for anti-HCV antibodies. The majority of HCV-seropositive women were in the third trimester of pregnancy, educated, and had a history of blood transfusion, abortion, surgery, or dentistry. Moreover, Arab and Fars pregnant women and those aged >39 years had the highest rate of HCV seroprevalence. Nevertheless, none of these variables were significantly associated with HCV seropositivity. In contrast, HCV seropositivity was associated with place of residency, so that residents of Khormuj city had significantly higher HCV seroprevalence compared to the residents of other cities (OR: 7.05; 95% CI: 1.75-28.39; P = 0.006). According to the molecular evaluation, 9 of the 19 HCV-seropositive pregnant women (47.37%) had HCV viremia with genotype 3a. CONCLUSION: This study reports the HCV prevalence of 1.33% for anti-HCV antibodies and 0.63% for HCV RNA among pregnant women in the south of Iran. Considering the asymptomatic nature of chronic HCV infection and the fact that vertical transmission is possible in women with detectable viremia, therefore, screening of women before pregnancy is recommended to reduce the risk of HCV infection and its complications during pregnancy.

Choosing spermatozoa with an optimum fertilizing potential is one of the major challenges in assisted reproductive technologies (ART). This selection is mainly based on semen parameters, but the addition of molecular approaches could allow a more functional evaluation. To this aim, we used sixteen fresh sperm samples from patients undergoing ART for male infertility and classified them in the high- and poor-quality groups, on the basis of their morphology at high magnification. Then, using a DNA sequencing method, we analyzed the spermatozoa methylome to identify genes that were differentially methylated. By Gene Ontology and protein-protein interaction network analyses, we defined candidate genes mainly implicated in cell motility, calcium reabsorption, and signaling pathways as well as transmembrane transport. RT-qPCR of high- and poor-quality sperm samples allowed showing that the expression of some genes, such as AURKA, HDAC4, CFAP46, SPATA18, CACNA1C, CACNA1H, CARHSP1, CCDC60, DNAH2, and CDC88B, have different expression levels according to sperm morphology. In conclusion, the present study shows a strong correlation between morphology and gene expression in the spermatozoa and provides a biomarker panel for sperm analysis during ART and a new tool to explore male infertility.

BACKGROUND: The association between heart failure (HF) and cognitive impairment has received increasing attention from scholars and researchers in recent years. However, no systematic studies have been carried out yet focused on the crosstalk between heart failure and cognitive impairment via miRNAs. METHODS: GSE104150, GSE53473, GSE120584, and GSE116250 with RNA-seq data and clinical data were downloaded from the GSE database. All data were statistically analysed using R software to detect DE-miRNAs and DE-mRNAs associated with both HF and cognitive impairment. Protein-protein interaction (PPI) networks were mapped, and a logistic regression model for cognitive impairment prediction was developed. Furthermore, the TTRUST database and miRWalk were used to map miRNA-transcription factor (TF) and messenger RNA (mRNA) regulatory pathways. Finally, core TFs were enriched for analysis. RESULTS: Differentially enriched DE-miRNAs and DE-mRNAs both present in HF and cognitive impairment were determined. A logistic regression model established based on DE-miRNAs was validated to have a strong performance in cognitive impairment prediction. The core miRNA-TF-mRNA pathway was formed by mapping the PPI networks associated with the two diseases. Further GSEA was performed with V-rel reticuloendotheliosis viral oncogene homolog B (RELB) as the core TF, and the retinol metabolism and gap junction pathways were analysed. CONCLUSIONS: This study was the first attempt to predict the crosstalk and examine underlying mechanisms between HF and cognitive impairment applying bioinformatics. The findings suggested a potential hsa-miR-933/RELB/CCL21 regulatory axis correlated with HF and neurological disorders (or cognitive impairment), according to PPI networks.

Osteoarthritis (OA) is a chronic degenerative musculoskeletal disease that causes articular cartilage degeneration and chronic pain. Research into OA animal models suggests that elevated NGF levels in the synovium contribute to pain and central sensitization (CS). However, it is unclear whether synovial NGF contributes to CS in patients with OA. We investigated the association between synovial NGF expression and clinical assessments of pain and CS in hip OA (hOA) patients. We also aimed to identify which cells in the synovium of hOA patients express NGF. Sixty-six patients who received total hip replacement and a diagnosis of hOA were enrolled. We measured NGF mRNA expression in synovial samples obtained from 50 patients using qPCR and analyzed the correlation of NGF expression with the CS inventory (CSI) score and Japanese Orthopaedic Association (JOA) score, a clinical scoring system for OA. To identify the synovial cells expressing NGF, we analyzed NGF mRNA expression in CD14+ and CD14- cells, which represent macrophage-rich and fibroblast-rich fractions, respectively, extracted from 8 patients. To further identify which macrophage subtypes express NGF, we examined NGF mRNA expression in CD14high and CD14low cells sorted from 8 patients. Synovial NGF mRNA expression was negatively correlated with JOA score but positively correlated with CSI score (JOA pain, r = -0.337, P = 0.017; CSI score, r = 0.358, P = 0.011). Significantly greater levels of NGF were observed in CD14- cells compared to CD14+ cells (P = 0.036) and in CD14high cells compared to CD14low cells (P = 0.008). In conclusion, synovial NGF expression is correlated with the degree of pain and CS in hOA patients. NGF is predominantly expressed in synovial fibroblasts. Further, CD14high synovial macrophages expressed higher levels of NGF. Our results may provide a novel NGF-targeted therapeutic strategy for hOA pain.

The aim of the present investigation was to evaluate the effect of the combined crude extract, fractions, and compound 1 isolated from the fruits of Datura metel against selected microbial (bacteria and fungi) strains. Results of antibacterial screening indicated marked susceptibility of the extract and its fractions against tested bacterial strains. Among the extract and various fractions, the chloroform fraction exhibited a significant effect against different bacterial strains including Escherichia coli, Staphylococcus aureus, and Bacillus subtilis with an inhibitory zone ranging from 18 to 24 mm. Similarly, results of antifungal activity revealed that the chloroform fraction displays a promising effect against various fungal strains. The chloroform fraction was subjected to repeated chromatography analysis, which yielded compound 1 (daturaolone). Daturaolone exhibited potent activity against selected bacterial strains including Klebsiella pneumoniae, B. subtilis, S. epidermidis, and S. aureus with an inhibitory zone ranging from 12 to 30 mm. In addition, the extracts and daturaolone exhibited significant sensitivity against T. longifusus, C. albicans, A. flavus, M. canis, F. solani, and C. glabrata. Taken all together, it is concluded that our findings validated the traditional use of D. metel to treat various infectious diseases, which is supported by daturaolone.

AIM: Psoriasis is a chronic inflammatory disease with a complex etiology, and psoriasis vulgaris (PsV) is the most common type of psoriasis. Recent studies suggest the relationship between psoriasis and metabolic syndrome in different ethnicities. This study is aimed at evaluating the association of metabolism-related gene variants with the risk of PsV in Chinese Han population. Material and Methods. PsV patients (1030) and healthy controls (965) were enrolled in this study. Eighteen single-nucleotide polymorphisms (SNPs) previously reported to be significantly associated with metabolic syndrome were selected. SNPs were detected by next-generation sequencing. RESULTS: Seven SNPs were significantly associated with PsV: rs805303 (P = 0.012, OR = 0.85), rs3177928 (P = 1.37 × 10-15, OR = 2.51), and rs2247056 (P = 3.73 × 10-4, OR = 0.67) located in the HLA gene region; rs1047781 (P = 0.012, OR = 1.18), rs281379 (P = 0.014, OR = 1.71), and rs492602 (P = 0.005, OR = 1.86) located in the FUT2 region; and rs2303138 (P = 0.014, OR = 1.18) located in the LNPEP region. After stratified analysis, rs805303 (P = 0.017, OR = 0.74) and rs2303138 (P = 0.041, OR = 1.30) were associated with PsVs when HLA-C∗06 : 02 was positive, and rs805303 (P = 5.62 × 10-5, OR = 0.68), rs3177928 (P = 0.003, OR = 1.75), rs281379 (P = 0.034, OR = 1.96), and rs492602 (P = 0.025, OR = 2.04) were associated with PsVs when HLA-C∗06 : 02 was negative. CONCLUSION: PsV and metabolic syndrome may have overlapped susceptible genes in Chinese Han population.

OBJECTIVES: We aimed to summarize the current evidence regarding the impact of extraction vs. nonextraction in orthodontic treatment on patients' soft-tissue profile with malocclusion. METHODS: Between April 30th and November 30th, 2020, we searched PubMed and SCOPUS for published papers from inception to November 2020 using "orthodontic," "extraction," "nonextraction," and "Malocclusion." Included studies were summarized, and relevant data were extracted and analyzed using Review Manager 5.4. RESULTS: Pooled data from four controlled trials demonstrated a nonsignificant difference between extraction and nonextraction in terms of SNA (MD = 0.50, 95% CI: -0.37, 1.38; p = 0.26), SNB (MD = 0.11, 95% CI: -1.23, 1.44; p = 0.88), FMA (MD = 1.82, 95% CI: -2.39, 6.02; p = 0.40), IMPA (MD = 0.06, 95% CI: -8.83, -8.94; p = 0.99), overjet (MD = -1.47, 95% CI: -6.21, 3.26; p = 0.54), and overbite (MD = 0.50, 95% CI: -1.40, 2.40; p = 0.60). On the other hand, the extraction method significantly increased the ANB compared with the nonextraction group (MD = 0.78, 95% CI: 0.25, 1.31; p = 0.004). CONCLUSION: The current evidence demonstrated that nonextraction protocols for orthodontic treatment are a safe and effective alternative to extraction protocols; individually tailored treatment strategies should be applied. More randomized controlled trials are critically needed to safely make an evidence-based treatment conclusion.

Dermatomyositis is an autoimmune disease characterized by severe symmetrical muscle dysfunction and pain. This study was aimed at discovering vital hub genes and potential molecular pathways of DM through bioinformatics analysis, which contributes to identifying potential diagnostic or therapeutic biomarkers and targets. In this study, a total of 915 DEGs in DM samples including 167 upregulated genes and 748 downregulated genes were screened out by the limma package based on the GSE142807 dataset from the Gene Expression Omnibus (GEO) database. Furthermore, the results of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicated that these downregulated genes were highly associated with the immune-related biological processes and pathways. Therefore, 41 genes closely related to DM were extracted for further study based on the subcluster analysis through the Molecular Complex Detection (MCODE) software plugin in Cytoscape. Ultimately, 10 hub genes (including ISG15, DDX58, IFIT3, CXCL10, and STAT1) were identified as the potential candidate biomarkers and targets. Besides, we found that the identified hub genes directly or indirectly communicated with each other via molecular signaling pathways on the protein and transcription level. In general, under the guidance of bioinformatics analysis, 10 vital hub genes and molecular mechanisms in DM were identified and the expression of proinflammatory factors and interferon family proteins and genes showed high association with DM, which might help provide a theoretical foundation for the development of point-to-point targeted therapy in the future treatment of DM.

BACKGROUND: In 2016, the World Health Organization (WHO) introduced a minimum of eight antenatal care (ANC) visits for positive pregnancy outcomes. This study examined the prevalence of noncompliance with 8+ ANCvisits and its associated factors in sub-Saharan Africa (SSA). METHODS: We used data from the Demographic and Health Surveys of eight countries in SSA. A pooled sample of 63,266 pregnant women aged 15-49 years who had given birth to children within 5 years prior to the surveys was included in this study. To examine the factors associated with noncompliance with ANC 8+ visits, multilevel binary logistic regression analysis was conducted, and the results were reported using odds radios at 95% confidence interval (CI). RESULTS: The pooled prevalence of noncompliance with ANC 8+ visits was 92.3% (95% CI: 91.1%-93.3%) with the highest and lowest prevalence in Zambia (98.7%, 95% CI: 98.3%-99.1%) and Libya (73.4%, 95% CI: 70.4%-76.2%), respectively. With the individual level factors, women's age (44-49 years-aOR = 0.33, 9% CI: 0.14-0.78), health insurance registration, (yes-aOR = 0.53, 95% CI: 0.29-0.98), and economic status (richest-aOR = 0.16, 95% CI: 0.05-0.49) were negatively associated with noncompliance with 8+ ANC visits, while parity (five or more children-aOR = 1.68, 95% CI: 1.12-2.52) was positively associated with noncompliance with 8+ ANC visit. With the community level factors, community level literacy was negatively associated with noncompliance with 8+ ANC visit (high-aOR = 0.56, 95% CI: 0.32-0.99). CONCLUSION: About eight out of ten pregnant women did not comply with the WHO's recommended minimum of eight ANC visits for positive pregnancy outcomes in SSA. Empowering the economic status of women , enhancing health insurance and education coverage, and giving more attention to young pregnant women and those with more children are crucial for improving the coverage of ANC 8+ visits in the region.

OBJECTIVE: To study the effect of pulsed radio frequency (PRF) on nerve repair and the expression of GFAP and GDNF in rats with neuropathic pain. METHODS: Thirty SPF healthy SD rats were randomly divided into control group (Group C), PSNL group (partial ligation of sciatic nerve) + sham group (Group PS), and PSNL group (partial ligation of sciatic nerve) + PRF group (Group PR), with 10 rats in each group. In group C, the right sciatic nerve was exposed without ligation. In the PS group, the model of neuropathic pain was established by partial ligation of sciatic nerve. The mice in the PR group were treated with PRF after establishing the neuropathic pain model. The general behavior of rats during the treatment was observed. The mechanical and thermal hyperalgesia were measured before operation and 1, 3, 7, and 14 days after operation. The content of inflammatory factors in nerve tissue was detected by ELISA. The pathological condition of nerve tissue was observed by HE. The gene and protein changes of GFAP and GDNF in nerve tissue were determined by QRT PCR and Western blot. RESULTS: Rats in the control group were free to move and in good condition. In the PS group, there were different degrees of claudication, weakness of the lower limbs, lateral toe valgus, nerve injury, and other behavioral changes. After the pulsed radiofrequency in the PR group, the above symptoms decreased gradually with the prolongation of the treatment time. The mechanical pain sensitivity and thermal allodynia of the PS group were reduced after the operation. The mechanical pain sensitivity and thermal pain sensitivity of the PR group gradually increased with the prolongation of the treatment time, and the 14 days were basically close to the control group. The levels of TNF-α and IL-6 in ELISA were significantly higher in the PS group than in the control group, and the content in the PR group was gradually reduced, which was close to the control group. HE staining showed that the sciatic nerve fibers disappeared, and the formation of nerve cavities was obvious in the 14-day PS group. The nerve fibers were found in the sciatic tissue of the PR group, and there was no obvious hemorrhagic edema and cell deformation. The expression of GFAP mRNA in the PS group was significantly higher than that in the control group and the PR group (p < 0.05), and the expression of GDNF was opposite (p < 0.05). The results of western blot showed that the expression of GFAP protein in the 14-day PS group was significantly higher than that in the control group. The expression of the PR group decreased compared with the control group, and the expression of GDNF was opposite (p < 0.05). CONCLUSION: Pulsed radiofrequency ablation can promote neurological repair, promote GDNF, and reduce the expression of GFAP in rats with neuropathic pain.

INTRODUCTION: Hypoglycemic drugs affect the bone quality and the risk of fractures in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and insulin on bone mineral density (BMD) in T2DM. METHODS: In this single-blinded study, a total of 65 patients with T2DM were randomly assigned into four groups for 52 weeks: the exenatide group (n = 19), dulaglutide group (n = 19), insulin glargine group (n = 10), and placebo (n = 17). General clinical data were collected, and BMD was measured by dual-energy X-ray absorptiometry. RESULTS: Compared with baseline, the glycosylated hemoglobin (HbA1c) decreased significantly in the exenatide (8.11 ± 0.24% vs. 7.40 ± 0.16%, P = 0.007), dulaglutide (8.77 ± 0.37% vs. 7.06 ± 0.28%, P < 0.001), and insulin glargine (8.57 ± 0.24% vs. 7.23 ± 0.25%, P < 0.001) groups after treatment. In the exenatide group, the BMD of the total hip increased. In the dulaglutide group, only the BMD of the femoral neck decreased (P = 0.027), but the magnitude of decrease was less than that in the placebo group; the BMD of L1-L4, femoral neck, and total hip decreased significantly (P < 0.05) in the placebo group, while in the insulin glargine group, the BMD of L2, L4, and L1-4 increased (P < 0.05). Compared with the placebo group, the BMD of the femoral neck and total hip in the exenatide group and the insulin glargine group were increased significantly (P < 0.05); compared with the exenatide group, the BMD of L4 in the insulin glargine group was also increased (P = 0.001). CONCLUSIONS: Compared with the placebo, GLP-1RAs demonstrated an increase of BMD at multiple sites of the body after treatment, which may not exacerbate the consequences of bone fragility. Therefore, GLP-1RAs might be considered for patients with T2DM. This trial is registered with ClinicalTrials.gov NCT01648582.

Exposure of the respiratory system to the Anisakis pegreffii L3 crude extract (AE) induces airway inflammation; however, the mechanism underlying this inflammatory response remains unknown. AE contains allergens that promote allergic inflammation; exposure to AE may potentially lead to asthma. In this study, we aimed to establish a murine model to assess the effects of AE on characteristic features of chronic asthma, including airway hypersensitivity (AHR), airway inflammation, and airway remodeling. Mice were sensitized for five consecutive days each week for 4 weeks. AHR, lung inflammation, and airway remodeling were evaluated 24 h after the last exposure. Lung inflammation and airway remodeling were assessed from the bronchoalveolar lavage fluid (BALF). To confirm the immune response in the lungs, changes in gene expression in the lung tissue were assessed with reverse transcription-quantitative PCR. The levels of IgE, IgG1, and IgG2a in blood and cytokine levels in the BALF, splenocyte, and lung lymph node (LLN) culture supernatant were measured with ELISA. An increase in AHR was prominently observed in AE-exposed mice. Epithelial proliferation and infiltration of inflammatory cells were observed in the BALF and lung tissue sections. Collagen deposition was detected in lung tissues. AE exposure increased IL-4, IL-5, and IL-13 expression in the lung, as well as the levels of antibodies specific to AE. IL-4, IL-5, and IL-13 were upregulated only in LLN. These findings indicate that an increase in IL-4+ CD4+ T cells in the LLN and splenocyte resulted in increased Th2 response to AE exposure. Exposure of the respiratory system to AE resulted in an increased allergen-induced Th2 inflammatory response and AHR through accumulation of inflammatory and IL-4+ CD4+ T cells and collagen deposition. It was confirmed that A. pegreffii plays an essential role in causing asthma in mouse models and has the potential to cause similar effects in humans.

INTRODUCTION: Management of acetabular fractures is challenging, especially when a medial acetabular fracture is complicated by central hip dislocation. We retrospectively investigated the clinical outcome and risk factors of secondary hip osteoarthritis requiring total hip arthroplasty after the surgical treatment of acetabular fractures with central hip dislocation. MATERIALS AND METHODS: The medical records of all patients who had acetabular medial wall fractures with central hip dislocation treated with open reduction and internal fixation by a single surgeon between January 2015 and June 2017 were reviewed. Surgical reduction was performed with the modified Stoppa with/without the Kocher-Langenbeck (KL) approach. Patients were followed for a minimum of three years, and the Majeed scoring system was used for functional evaluation. Multivariate logistic regression analysis was used to assess the association of patients' characteristics with the likelihood of advanced posttraumatic arthritis developing with conversion to total hip arthroplasty. RESULTS: Fifty patients were included in this study, with disease classified as AO/OTA 2018 62B/62C. Thirty-five patients (70%) had good or excellent Majeed pelvic scores. Eleven patients (22%) eventually received total hip arthroplasty because of end-stage posttraumatic arthritis. Three risk factors identified for total hip arthroplasty were male sex, initial marginal impaction, and sciatic nerve injury. Kaplan-Meier survivorship analysis estimated that the cumulative probability of free-from-end-stage arthritis was 78% (95% confidence interval, 73%-90%) at the 5-year follow-up. CONCLUSION: Surgical fixation with the modified Stoppa and the KL approach for acetabular medial wall fractures with central hip dislocation is an effective approach with a satisfactory functional outcome. A prodromal factor was marginal impaction concomitant with articular damage. The trauma of high axial loading and the occupational distribution (males performing heavy manual labor and heavy lifting) with preoperative sciatic nerve injury increased the odds of developing end-stage arthritis.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is a major health problem worldwide, and neurologic injury remains the leading cause of morbidity and mortality among survivors of OHCA. The purpose of this study was to investigate whether a machine learning algorithm could detect complex dependencies between clinical variables in emergency departments in OHCA survivors and perform reliable predictions of favorable neurologic outcomes. METHODS: This study included adults (≥18 years of age) with a sustained return of spontaneous circulation after successful resuscitation from OHCA between 1 January 2004 and 31 December 2014. We applied three machine learning algorithms, including logistic regression (LR), support vector machine (SVM), and extreme gradient boosting (XGB). The primary outcome was a favorable neurological outcome at hospital discharge, defined as a Glasgow-Pittsburgh cerebral performance category of 1 to 2. The secondary outcome was a 30-day survival rate and survival-to-discharge rate. RESULTS: The final analysis included 1071 participants from the study period. For neurologic outcome prediction, the area under the receiver operating curve (AUC) was 0.819, 0.771, and 0.956 in LR, SVM, and XGB, respectively. The sensitivity and specificity were 0.875 and 0.751 in LR, 0.687 and 0.793 in SVM, and 0.875 and 0.904 in XGB. The AUC was 0.766 and 0.732 in LR, 0.749 and 0.725 in SVM, and 0.866 and 0.831 in XGB, for survival-to-discharge and 30-day survival, respectively. CONCLUSIONS: Prognostic models trained with ML technique showed appropriate calibration and high discrimination for survival and neurologic outcome of OHCA without using prehospital data, with XGB exhibiting the best performance.

Diabetes mellitus termed as metabolic disorder is a collection of interlinked diseases and mainly body's inability to manage glucose level which leads to cardiovascular diseases, renal failure, neurological disorders, and many others. The drugs contemporarily used for diabetes have many inevitable side effects, and many of them have become less responsive to this multifactorial disorder. Momordica charantia commonly known as bitter gourd has many bioactive compounds with antidiabetic properties. The current study was designed to use computational methods to discover the best antidiabetic peptides devised from hypoglycemic polypeptide-P of M. charantia. The binding affinity and interaction patterns of peptides were evaluated against four receptor proteins (i.e., as agonists of insulin receptor and inhibitors of sodium-glucose cotransporter 1, dipeptidyl peptidase-IV, and glucose transporter 2) using molecular docking approach. A total of thirty-seven peptides were docked against these receptors. Out of which, top five peptides against each receptor were shortlisted based on their S-scores and binding affinities. Finally, the eight best ligands (i.e., LIVA, TSEP, EKAI, LKHA, EALF, VAEK, DFGAS, and EPGGGG) were selected as these ligands strictly followed Lipinski's rule of five and exhibited good ADMET profiling. One peptide EPGGGG showed activity towards insulin and SGLT1 receptor proteins. The top complex for both these targets was subjected to 50 ns of molecular dynamics simulations and MM-GBSA binding energy test that concluded both complexes as highly stable, and the intermolecular interactions were dominated by van der Waals and electrostatic energies. Overall, the selected ligands strongly fulfilled the drug-like evaluation criterion and proved to have good antidiabetic properties.

OBJECTIVE: Examining the effects of a pulmonary rehabilitation (PR) program applied to patients undergoing coronary artery bypass grafting (CABG) surgery with open heart technique on respiratory functions, functional capacity, and quality of life (QoL). DESIGN: This randomised controlled study applied the Consolidated Standards of Reporting Trials statement. METHODS: The study was conducted with two groups: the intervention group (n = 25) and the control group (n = 25). The control group received standard care after coronary artery bypass grafting. On the contrary, the experimental group participated in a PR program created by the researchers in addition to standard care. After coronary artery bypass grafting, the respiratory functions (on the 4th day of clinical care) and QoL (at the 6th week) of both groups were evaluated. The primary outcome measure was the respiratory function (forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC). The secondary outcome measure of this study was the QoL. RESULTS: When the average pulmonary function test values of the patients were examined, the mean FVC and FEV1 values of the patients in the intervention group on the 4th day of clinical care were significantly higher with a medium level size effect than the control group (p = 0.027; effect size (d) = 0.643; p < 0.024; effect size (d) = 0.658, respectively). At the postoperative 6th week measurement of QoL, a decrease was observed in all subdimensions of the scale, albeit less in the intervention group (p < 0.05). There was a decrease in both the mental and physical component summary of QoL (p < 0.05). CONCLUSION: The results of this study revealed that pulmonary rehabilitation applied to patients who have undergone coronary artery bypass graft recover their functional capacity faster.

Unreacted monomers eluted from resin-based restorative materials have been considered a reason of local and systemic adverse reactions. This study was designed to determine the effect of finishing and polishing procedures on the elution of Bis-GMA, TEGDMA, UDMA, and HEMA monomers from compomer and bulk-fill composite resins. Bulk-fill composite (3M ESPE GmbH, Seefeld, Germany) and compomer (Dentsply DeTrey GmbH, Konstanz, Germany) specimens with 3 × 4 mm diameters were prepared. The specimens were randomly divided into two groups, and finishing-polishing procedures were applied only to the experimental groups. Release of residual monomers was analyzed by using High-Performance Liquid Chromatography (HPLC) after 24, 48, and 72 hours. Repeated measures ANOVA and Tukey post hoc tests were used for comparisons. Finishing and polishing procedures had a significant effect on reducing the quantity of UDMA release in the Filtek™ Bulk Fill composite and Bis-GMA, HEMA, and TEGDMA in the Dyract XP compomer (p < 0.05). The restorative materials investigated here are not chemically stable after polymerization, and concentrations of eluted monomers may reach critical toxicity levels even after one restoration placement. Finishing and polishing procedures are mandatory to reduce residual monomers.

This study reports the development of thermosensitive hydrogels for delivering ropivacaine (RVC), a wide clinically used local anesthetic. For this purpose, poloxamer- (PL-) based hydrogels were synthesized for evaluating the influence of polymer concentration, hydrophilic-lipophilic balances, and binary system formation on biopharmaceutical properties and pharmacological performance. Transition temperatures were shifted, and rheological analysis revealed a viscoelastic behavior with enhanced elastic/viscous modulus relationship (G'/G " = 1.8 to 22 times), according to hydrogel composition and RVC incorporation. The RVC release from PL407 and PL407/338 systems followed the Higuchi model (R 2 = 0.923-0.989), indicating the drug diffusion from hydrogels to the medium. RVC-PL hydrogels were potentially biocompatible evoking low cytotoxic effects (in fibroblasts and Schwann cells) and mild/moderate inflammation signs on sciatic nerve nearby histological evaluation. In vivo pharmacological assays demonstrated that PL407 and PL407/338 evoked differential analgesic effects, by prolonging the sensory blockade duration up to ~340 and 250 min., respectively. All those results highlighted PL407 and PL407/338 as promising new strategies for sustaining analgesic effects during the postoperative period.

The prolapsed intervertebral disc (PIVD) at the lumbar spine is one of the most common causes of low back pain (LBP) affecting humans worldwide. Lumbar traction is widely used as a part of physiotherapeutic modalities for its treatment; however, reports on its effectiveness and dosage are conflicting. This study is aimed at comparing the acute effects of three traction forces on the straight leg raise (SLR) test and LBP intensity. A total of 45 (age 35.53 yrs., ±3.09) participants with 15 participants in each group were recruited for the study. Participants were divided into groups A, B, and C wherein traction forces equal to one-fifth, one-third, and one-half of their bodyweight were applied, respectively. SLR range of motion (ROM) and pain were examined before and immediately after the application of traction. Significant improvement was observed in SLR ROM in all three groups (p < 0.05). However, for pain, significant improvement (p < 0.05) was observed only in the group with one-half of bodyweight force. There was no significant difference (p > 0.05) between the three groups for both variables. All three forces were equally effective in immediately improving SLR ROM in patients suffering from lumbar PIVD; however, pain improvement was observed with one-half of bodyweight only.

The Labisia pumila (LP) is a traditional plant that is locally known as Kacip Fatimah, Selusuh Fatimah, or Pokok Ringgang by the Malaysian indigenous people. It is believed to facilitate their childbirth, treating their postchild birth and menstrual irregularities. The water extract of LP has shown to contain bioactive compounds such as flavonoids, ascorbic acid, β-carotene, anthocyanin, and phenolic acid, which contribute extensive antioxidant, anti-inflammatory, antimicrobial, and antifungal. The LP ethanolic extract exhibits significant estrogenic effects on human endomentrial adenocarcinoma cell in estrogen-free basal medium and promoting an increase in secretion of alkaline phosphate. Water based has been used for many generations, and studies had reported that it could displace in binding the antibodies and increase the estradiol production making it similar to esterone and estradiol hormone. LP extract poses a potential and beneficial aspect in medical and cosmeceutical applications. This is mainly due to its phytoestrogen properties of the LP. However, there is a specific functionality in the application of LP extract, due to specific functional group in phytoconstituent of LP. Apart from that, the extraction solvent is important in preparing the LP extract as it poses some significant and mild side effects towards consuming the LP extracts. The current situation of women reproductive disease such as postmenopausal syndrome and polycystic ovary syndrome is increasing. Thus, it is important to find ways in alternative treatment for women reproductive disease that is less costly and low side effects. In conclusion, these studies proven that LP has the potential to be an alternative way in treating female reproductive related diseases such as in postmenopausal and polysystic ovarian syndrome women.

Periodontitis comprises a chronic inflammation that is initiated by microbiota biofilm. If left untreated, periodontitis may lead to permanent tooth loss. Herein, we propose to design and improve a localized form of therapy comprising a chlorhexidine-impregnated hydrogel. Hydrogel films were prepared by varying the ratio between cellulose (MCC) and carboxymethylcellulose sodium (CMC) using the crosslinker epichlorohydrin (ECH). The hydrogel was loaded with chlorhexidine. Increasing the CMC ratio led to a reduction in the number of pores, an increase in their size, lower glass transition temperature (T g ), decreased Young's modulus, and increased film stretching and affected the time of release. Bacterial and fungal zones of inhibition showed similar activity and were not affected by the CMC and MCC ratio. Hydrogels loaded with chlorhexidine prevented the growth of S. oralis and C. albicans microorganisms and may provide a promising local delivery system for treating periodontitis.

A full-thickness skin graft (FTSG) is useful for covering small skin and soft tissue defects. In this paper, we suggest FTSG in consideration of the relaxed skin tension line (RSTL) concept for scar quality improvement since FTSG has disadvantages, including contour irregularities and mismatches of color and texture. We conducted a retrospective chart review of twenty-one patients with skin cancer on the face who underwent wide excision and FTSG by a single surgeon from October 2013 to July 2019. Twenty-one patients with skin cancer on the face were divided into RSTL-matched and RSTL-unmatched groups, and FTSG was performed. Each group was subjected to scar assessment three months after surgery. Observer assessment was performed by five independent observers using the observer component of the patient and observer scar assessment scale (POSAS) and Vancouver scar scale (VSS). Our results indicate that there were significant differences between the RSTL-matched and RSTL-unmatched groups in the VSS and POSAS components. In addition, the RSTL-matched group showed a natural appearance with surrounding tissue in the dynamic animation phase compared to the unmatched group. RSTL-matched FTSG can be an attractive option for face skin and soft tissue defect coverage. (An earlier version of this paper has been presented at the International Conference on PRS Korea 2020.).

In the clinical settings, different anthropometric indicators like neck circumference (NC), waist circumference (WC), midupper arm circumference (MUAC), waist-to-height ratio (WHtR), and arm-to-height ratio (AHtR) have been suggested for evaluating overweight and obesity in children. The comparative ability of these indicators in Pakistan is yet unknown. This study is aimed at examining the validity of different anthropometric indicators of overweight and obesity simultaneously and at determining their superlative cut-off values that would correctly detect overweight and obesity in children. For this purpose, the dataset of anthropometric measurements height, weight, WC, MUAC, and NC of 5,964 Pakistani children, aged 5-12 years collected in a cross-sectional multiethnic anthropometric survey (MEAS), was used. Receiver operating characteristic (ROC) curve analysis was performed to assess the validity of different anthropometric indicators. The most sensitive and specific cut-off points, positive and negative predictive values of each indicator were also calculated. The results of the ROC curve indicated that all the studied indicators had a good performance but the indicators AHtR and WHtR had the highest value of the area under the curve (AUC) for the screening of children with overweight and obesity (AUC > 0.80). In the overall sample, AHtR, WHtR, MUAC, WC, and NC cut-off points indicative of overweight, in both boys and girls, were 0.14, 0.46, 18.41 cm, 62.86 cm, and 26.36 cm and 0.14, 0.47, 18.16 cm, 64.39 cm, and 26.54 cm, respectively; the corresponding values for obesity were 0.14, 0.47, 18.67 cm, 62.10 cm, and 26.36 cm and 0.14, 0.48, 20.19 cm, 64.39 cm, and 25.27 cm. We concluded that the sex-specific cut-off points for AHtR, WHtR, MUAC, WC, and NC can be used to diagnose overweight and obesity in Pakistani children.

Disease caused by antibiotic-resistant Salmonella is a serious clinical problem that poses a great threat to public health. The present study is aimed at assessing differences in bacterial kinetics with different antibiotic resistance profiles under environmental stress and at developing microbial tolerance models in lettuce during storage from 4 to 36°C. The drug-resistance phenotypes of 10 Salmonella Typhimurium (S. Typhimurium) isolates were examined using the broth microdilution method. The results of 10 S. Typhimurium isolates in the suspensions showed that a slow trend towards reduction of drug-sensitive (DS) isolates in relation to the others though without statistical difference. Compared to DS S. Typhimurium SA62, greater bacterial reduction was observed in multidrug-resistant (MDR) S. Typhimurium HZC3 during lettuce storage at 4°C (P < 0.05). It was likely that a cross-response between antibiotic resistance and food-associated stress tolerance. The greater growth in lettuce at 12°C was observed for DS S. Typhimurium SA62 compared to MDR S. Typhimurium HZC3 and was even statistically different (P < 0.05), while no significant difference was observed for bacterial growth between MDR S. Typhimurium HZC3 and DS S. Typhimurium SA62 strains in lettuce storage from 16 to 36°C (P > 0.05). The goodness-of-fit indices indicated the Log-linear primary model provided a satisfactory fit to describe the MDR S. Typhimurium HZC3 and DS S. Typhimurium SA62 survival at 4°C. A square root secondary model could be used to describe the effect of temperature (12, 16, 28, and 36°C) on the growth rates of S. Typhimurium HZC3 (adj - R 2 = 0.91, RMSE = 0.06) and S. Typhimurium SA62 (adj - R 2 = 0.99, RMSE = 0.01) derived from the Huang primary model. It was necessary to pay attention to the tolerance of antibiotic resistant bacteria under environmental stress, and the generated models could provide parts of the input data for microbial risk assessment of Salmonella with different antibiotic resistance profile in lettuce.

BACKGROUND: The relationship between tuberculosis (TB) and adverse pregnancy outcomes remains unclear. The aim of our study was to investigate whether TB is a risk factor for adverse pregnancy outcomes including premature birth, low birth weight, and stillbirth. METHOD: We conducted a population-based retrospective cohort study in mainland China. A total of 3,668,004 Chinese women, along with their partners, were included in this study, within the National Free Pre-Pregnancy Checkups Project, during 2015-2018. Propensity score matching was used to balance the two groups (cases: women or partners with TB; controls: women and partners without TB). Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Multivariate logistic regression showed that the OR of stillbirth for cases was 1.89 (95% CI: 1.09-3.16), in comparison with the control group. In the subgroup analysis, women whose partner had TB had a higher risk of stillbirth (OR: 2.13, 95% CI: 1.10-3.86) than women whose partner did not have TB. There was no significant difference in adverse pregnancy outcomes, including preterm birth, low birth weight, and stillbirth, between women with and without TB. CONCLUSIONS: Women whose partner had TB were more likely to have stillbirth than women whose partners did not have TB.

Early sexual initiation is linked to an increased risk of HIV/AIDS and other STIs among teenagers, as well as having multiple partners, not using contraception, unintended pregnancy, and illegal abortions. Aim. To identify the correlates and psychological effects of early sexual debut among not-in-union women in Ghana. A descriptive cross-sectional survey was used for this study using data from Ghana Multiple Indicator Cluster Survey (MICS) for the year 2017/2018. SPSS software was used for data analysis, bivariate analysis for association was done using chi-square, and the prediction was done using a binary logistic regression model. The national prevalence of nonmarital early sexual initiation this current study recorded was 56.9%. Predictors variables were age, 15-24/≥35 years (AOR = 1.51, 1.28-1.78), ever educated (AOR = 0.50, 0.43-0.60), urban address (AOR = 0.85, 0.74-0.98), married/single (AOR = 1.23, 1.07-1.42), cohabitation/single (AOR = 1.43, 1.19-1.72), Greater Accra Region/Upper West Region (AOR = 0.67, 0.49-0.92), and health insurance (AOR = 0.89, 0.79-0.998). As the wealth indices of the woman decrease from the richest to poorest, the likelihood of early sexual debut inversely increases: fourth/richest (AOR = 1.23, 1.04-1.45), middle/richest (AOR = 1.31, 1.09-1.58), second/richest (AOR = 1.38, 1.11-1.72), and poorest/richest (AOR = 1.44, 1.12-1.86); use of the internet (AOR = 0.58, 0.50-068); substance use and alcohol ever use (AOR = 1.32, 1.17-1.49); cigarette ever use (AOR = 2.58, 1.44-4.64); contraceptive use (AOR = 1.31, 1.16-1.49); and ever heard of HIV (AOR = 59, 0.42-0.82). In conclusion, the prevalence of early sexual debut is still high in Ghana, especially among the northern regions. Several factors predicted early sex debut, and low life satisfaction and happiness were related to early sexual debut.

INTRODUCTION: Distinct from other diseases, as cancer progresses, both the symptoms and treatments evolve, resulting in a complex, time-dependent relationship. Many competing risk factors influence the outcome of cancer. An improved method was used to evaluate the data from 6 non-small-cell lung cancer (NSCLC) clinical trials combined in our center since 2016 to deal with the bias caused by competing risk factors. Material and Methods. Data of 118 lung cancer patients were collected from 2016 to 2020. Fine and Gray's model for competing risk was used to evaluate survival of different treatment group compares with the classic survival analysis model. RESULTS: Immunotherapy had better progression-free survival than chemotherapy. (HR: 0.62, 95% CI: 0.41-0.95, p = 0.0260). However, there were no significant differences in patients who withdrew due to treatment-related adverse events from different groups. (Z = 0.0508, p = 0.8217). The PD-1/PD-L1 inhibitors in our study did not significantly improve overall survival compared with chemotherapy (HR:0.77, 95% CI:0.48-1.24, p = 0.2812), estimated 1-year overall survival rates were 55% and 46%, and 3-year overall survival rates were 17% and 10%, respectively. CONCLUSION: When the outcome caused by competing risk exists, the corresponding competing risk model method should be adopted to eliminate the bias caused by the classic survival analysis.

BACKGROUND: Despite the relevance of cold chain management in maintaining the potency of vaccines, gaps still exist in the ability of healthcare practitioners to maintain the cold chain system effectively. Thus, the current study sought to assess healthcare providers' knowledge, attitudes, practices, and challenges regarding cold chain management. METHODS: A concurrent mixed methods study was conducted at twelve facilities in the Sekyere Central District of Ghana. Eighty-six (86) participants took part in a survey that assessed their "cold chain management" knowledge and attitudes. Twelve (12) cold chain sites within the district were also observed in respect of their cold chain management practices. Eleven key informants were additionally interviewed to explore their challenges on cold chain management. Quantitative data were analyzed using descriptive (frequencies, percentages, means, standard deviations, ranges) and inferential statistics (Spearman's rho correlation). Qualitative data were inductively analyzed into themes which described participants' challenges on cold chain management. RESULTS: Majority of the participants scored ≥70% on knowledge (68.6%) and attitudes (67.4%) toward cold chain management. However, there was a very weak positive and statistically insignificant relationship between participant's knowledge and attitudes toward cold chain management (r = 0.109, p = 0.317). Regarding cold chain management practices, majority of the facilities had their vaccine vial monitors attached to the vaccines (8/12, 66.7%), had functional fridge tags (8/12, 66.7%), and an appropriate refrigerator to store vaccines (7/12, 58.3%). However, the study observed that 91.7% (11/12) of the facilities did not have policies and guidelines on cold chain management while all 12 facilities (100%) did not have a contingency plan in place for equipment. With regards to the cold chain management challenges, participants raised concerns about inadequate personnel, erratic power supply, logistical constraints, and transportation difficulties. CONCLUSION: Although majority of the participants had good knowledge and attitude towards cold chain management, there was a weak association between them. This implies that good knowledge may not necessarily influence good attitudes towards cold chain management and vice versa. The extent to which facilities support cold chain management practices was suboptimal. Participants encountered a number of challenges which prevented them from managing the vaccine cold chain system effectively. We recommend continual professional education for cold chain practitioners, provision of adequate human and material resources for cold chain management, and enhanced monitoring and evaluation of cold chain activities. Future studies should quantitatively measure individual participants' knowledge, attitudes, practices, and challenges on cold chain management so that we can establish the relationships that exist between these components.

Type 2 diabetes (T2D) is one of the most common chronic metabolic disorders in adulthood worldwide, whose pathophysiology includes an abnormal immune response accompanied by cytokine dysregulation and inflammation. As the T2D-related inflammation and its progression were associated with the balance between pro and anti-inflammatory cytokines, anticytokine treatments might represent an additional therapeutic option for T2D patients. This review focuses on existing evidence for antihyperglycemic properties of disease-modifying antirheumatic drugs (DMARDs) and anticytokine agents (anti-TNF-α, anti-interleukin-(IL-) 6, -IL-1, -IL-17, -IL-23, etc.). Emphasis is placed on their molecular mechanisms and on the biological rationale for clinical use. Finally, we briefly summarize the results from experimental model studies and promising clinical trials about the potential of anticytokine therapies in T2D, discussing the effects of these drugs on systemic and islet inflammation, beta-cell function, insulin secretion, and insulin sensitivity.

AIMS: Few research was reported to explore oxidative stress in individuals with latent autoimmune diabetes in adults (LADA). Therefore, our goal is to study oxidative stress and related factors in LADA patients. METHODS: In this study, 250 Chinese inpatients were diagnosed with LADA (n = 110) and type 2 diabetes mellitus (n = 140) and 140 healthy volunteers were recruited. Moreover, individuals with LADA were followed for 6 months to evaluate whether short-term glycemic control during hospitalization can improve oxidative stress. Clinical and laboratory measurements of height, weight, blood pressure, glycosylated hemoglobin (HbA1c), blood lipids, 8-isoprostaglandin F2α (8-iso-PGF2α), and superoxide dismutase (SOD) were performed. Stepwise multiple regression analyses were used to assess factors that related to oxidative stress in individuals with LADA. RESULTS: Compared with patients with type 2 diabetes, individuals with LADA have better oxidative stress and worse oxidative stress than healthy volunteers. After multiple regression analyses, systolic blood pressure, HbA1c, duration of diabetes, and diabetic retinopathy were associated with 8-iso-PGF2α and HbA1c. Diabetic retinopathy and diabetic ketosis were associated with SOD in individuals with LADA. Our results also revealed that, after 6 months of follow-up, oxidative stress was improved to some extent in persons with LADA. CONCLUSIONS: Our results show that compared with type 2 diabetes, LADA means less oxidative stress, and compared with healthy volunteers, it means more oxidative stress. Systolic blood pressure, HbA1c, duration of diabetes, diabetic retinopathy, and ketosis were associated with oxidative stress in individuals with LADA. Furthermore, short-term glycemic control can improve oxidative stress to some extent in individuals with LADA.

Clostridioides difficile infection (CDI) is a health issue of utmost significance in Europe and North America, due to its high prevalence, morbidity, and mortality rate. The clinical spectrum of CDI is broad, ranging from asymptomatic to deadly fulminant colitis. When associated with chronic kidney disease (CKD), CDI is more prevalent and more severe than in the general population, due to specific risk factors such as impaired immune system, intestinal dysmotility, high antibiotic use leading to disturbed microbiota, frequent hospitalization, and PPI use. We performed a systematic review on the issue of prevention and treatment of CDI in the CKD population, analysing the suitable randomized controlled cohort studies published between 2000 and 2021. The results show that the most important aspect of prevention is isolation and disinfection with chlorine-based solution and hydrogen peroxide vapour to stop the spread of bacteria. In terms of prevention, using Lactobacillus plantarum (LP299v) proved to be more efficient than disinfection measures in transplant patients, leading to higher cure rates and less recurrent episodes of CDI. Treatment with oral fidaxomycin is more effective than with oral vancomycin for the initial episode of CDI in CKD patients. Faecal microbiota transplantation (FMT) is more effective than vancomycin in recurrent CDI in CKD patients. More large-sample RCTs are necessary to conclude on the best treatment and prevention strategy of CDI in CKD patients.

The study is aimed at studying the association between the levels of serum adiponectin (ADPN), high-sensitivity C-reactive protein (hs-CRP), and soluble intercellular adhesion molecule-1 (sICAM-1) and hypertensive cerebrovascular complications. 50 patients with hypertensive cerebrovascular disease treated in Gansu Provincial Hospital from December 2016 to December 2018 were selected as the experimental group, and 50 normal people who underwent physical examination were selected as the control group. The blood pressure, heart rate, and the complications were recorded, and the serum blood lipid indexes were detected. Moreover, the content of serum ADPN, hs-CRP, and sICAM-1; the neurological indexes; brain-derived neurotrophic factor (BNDF); and neurone-specific enolase (NSE) were also determined using ELISA. The content of aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and serum creatinine (SCR) in the experimental group was significantly higher than that in control group (p < 0.05); the incidence of cerebrovascular complications, systolic blood pressure, diastolic blood pressure, and heart rate increased (p < 0.05); the content of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), hs-CRP, and sICAM-1 obviously rose (p < 0.05); and the content of ADPN and HDL obviously declined (p < 0.05). Besides, the experimental group had evidently lower systolic blood flow velocity (Vs), diastolic blood flow velocity (Vd), and mean blood flow velocity (Vm) and evidently higher pulsatility index (PI) (p < 0.05). The levels of S100 and NSE in the experimental group increased significantly, and the level of BNDF decreased significantly (p < 0.05). In patients with hypertensive cerebrovascular disease, the level of ADPN declines; the levels of hs-CRP and sICAM-1 rise; the incidence rate of cerebrovascular complications is elevated; and there are changes in the blood lipid, cerebrovascular hemodynamic, and neurological indexes, thereby further promoting the occurrence and development of hypertensive cerebrovascular disease.

PURPOSE: To determine the effects of cataract surgery and preoperative factors on the vision-related quality of life (QOL) in patients with retinitis pigmentosa (RP). MATERIALS AND METHODS: This was a prospective, interventional study of 54 patients diagnosed with RP. The 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was used to determine the QOL before and after the cataract surgery. The correlations between the scores of the questionnaire and the best-corrected visual acuity (BCVA), macular structure, and degree of improvement of the NEI VFQ-25 scores were also determined. RESULTS: Statistically significant improvements were observed in the BCVA and all of the NEI VFQ-25 subscale scores except for color vision. The improvement of general vision was the largest. The postoperative BCVA of the better-seeing eye was more strongly and significantly correlated with the postoperative NEI VFQ-25 scores than that of the worse-seeing eye. All of the postoperative NEI VFQ-25 scores were significantly correlated with the length of the ellipsoid zone (EZ) of the photoreceptors. No significant correlation was found between the preoperative general vision, near vision, mental health scores, and EZ length. All of the preoperative NEI VFQ-25 scores except the social function and mental health scores were negatively and significantly correlated with the degree of improvement of the NEI VFQ-25 score. The EZ length was significantly correlated with the degree of improvement of the NEI VFQ-25 scores of the general vision, distance vision, mental health, dependency, and composite 9 scores. CONCLUSIONS: Cataract surgery can significantly improve the NEI VFQ-25 scores in RP patients. The EZ length can be used to predict the postoperative VFQ scores. We conclude that the NEI VFQ-25 is a useful method to evaluate the impact of cataract surgery on the BCVA in patients with RP.

BACKGROUND: Systemic lupus erythematosus (SLE) is a refractory immune disease, which is often complicated with osteonecrosis of the femoral head (ONFH). Curcumin, the most active ingredient of Curcuma longa with a variety of biological activities, has wide effects on the body system. The study is aimed at exploring the potential therapeutic targets underlying the effect of curcumin on SLE-ONFH by utilizing a network pharmacology approach and molecular docking strategy. METHODS: Curcumin and its drug targets were identified using network analysis. First, the Swiss target prediction, GeneCards, and OMIM databases were mined for information relevant to the prediction of curcumin targets and SLE-ONFH-related targets. Second, the curcumin target gene, SLE-ONFH shared gene, and curcumin-SLE-ONFH target gene networks were created in Cytoscape software followed by collecting the candidate targets of each component by R software. Third, the targets and enriched pathways were examined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Eventually, a gene-pathway network was constructed and visualized by Cytoscape software; key potential central targets were verified and checked by molecular docking and literature review. RESULTS: 201 potential targets of curcumin and 170 related targets involved in SLE-ONFH were subjected to network analysis, and the 36 intersection targets indicated the potential targets of curcumin for the treatment of SLE-ONFH. Additionally, for getting more comprehensive and accurate candidate genes, the 36 potential targets were determined to be analyzed by network topology and 285 candidate genes were obtained finally. The top 20 biological processes, cellular components, and molecular functions were identified, when corrected by a P value ≤ 0.05. 20 related signaling pathways were identified by KEGG analysis, when corrected according to a Bonferroni P value ≤ 0.05. Molecular docking showed that the top three genes (TP53, IL6, VEGFA) have good binding force with curcumin; combined with literature review, some other genes such as TNF, CCND1, CASP3, and MMP9 were also identified. CONCLUSION: The present study explored the potential targets and signaling pathways of curcumin against SLE-ONFH, which could provide a better understanding of its effects in terms of regulating cell cycle, angiogenesis, immunosuppression, inflammation, and bone destruction.

There have been various developments in intraoral 3D scanning technology. This study is aimed at investigating the accuracy of 10 scanners developed from 2015 to 2020. A maxillary dental model with reference points was printed from Form 2 (FormLabs, Somerville, MA, USA). The model was scanned 5 times with each intraoral scanner (IOS); Trios 3 (normal and high-resolution mode); Trios 4 (normal and high-resolution mode) (3Shape Trios A/S, Copenhagen, Denmark); iTero Element, iTero 2, and iTero 5D Element (Align Technologies, San Jose, California, USA); Dental Wings (Dental Wings, Montreal QC, Canada); Panda 2 (Pengtum Technologies, Shanghai, China); Medit i500 (Medit Corp. Seoul, South Korea); Planmeca Emerald™ (Planmeca, Helsinki, Finland); and Aoralscan (Shining 3D Tech. Co., Ltd., Hangzhou, China). After the scan, the 3D scanned stereolithography files were created. The various distances were measured five times in X, Y, Z, and XY axes of various scans and with a vernier caliper (control) and from the Rhinoceros software. The data were analyzed using SPSS 18. Test for the normality of the various measurement data were done using Kolmogorov-Smirnov test. The trueness and precision of the measurements were compared among the various scans using the Kruskal-Wallis test. The significance was considered at P < 0.05. The trueness of the intraoral scans was analyzed by comparing the measurements from the control. Precision was tested through the measurements of repeated scans. It showed that more the distance is less the accuracy for all scanners. In all studied scanners, the trueness varied but precision was favorably similar. Diagonal scanning showed less accuracy for all the scanners. Hence, when scanning the full arch, the dentist needs to take more caution and good scan pattern. Trios series showed the best scan results compared to other scanners.

Acute coronary syndrome (ACS) is a complex syndrome of clinical symptoms. In order to accurately diagnose the type of disease in ACS patients, this study is aimed at exploring the differentially expressed genes (DEGs) and biological pathways between acute myocardial infarction (AMI) and unstable angina (UA). The GSE29111 and GSE60993 datasets containing microarray data from AMI and UA patients were downloaded from the Gene Expression Omnibus (GEO) database. DEG analysis of these 2 datasets is performed using the "limma" package in R software. DEGs were also analyzed using protein-protein interaction (PPI), Molecular Complex Detection (MCODE) algorithm, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Correlation analysis and "cytoHubba" were used to analyze the hub genes. A total of 286 DEGs were obtained from GSE29111 and GSE60993, including 132 upregulated genes and 154 downregulated genes. Subsequent comprehensive analysis identified 20 key genes that may be related to the occurrence and development of AMI and UA and were involved in the inflammatory response, interaction of neuroactive ligand-receptor, calcium signaling pathway, inflammatory mediator regulation of TRP channels, viral protein interaction with cytokine and cytokine receptor, human cytomegalovirus infection, and cytokine-cytokine receptor interaction pathway. The integrated bioinformatical analysis could improve our understanding of DEGs between AMI and UA. The results of this study might provide a new perspective and reference for the early diagnosis and treatment of ACS.

Three-dimensional (3D) bioprinting is a revolutionary technology that replicates 3D functional living tissue scaffolds in vitro by controlling the layer-by-layer deposition of biomaterials and enables highly precise positioning of cells. With the development of this technology, more advanced research on the mechanisms of tissue morphogenesis, clinical drug screening, and organ regeneration may be pursued. Because of their self-renewal characteristics and multidirectional differentiation potential, induced pluripotent stem cells (iPSCs) have outstanding advantages in stem cell research and applications. In this review, we discuss the advantages of different bioinks containing human iPSCs that are fabricated by using 3D bioprinting. In particular, we focus on the ability of these bioinks to support iPSCs and promote their proliferation and differentiation. In addition, we summarize the applications of 3D bioprinting with iPSC-containing bioinks and put forward new views on the current research status.

OBJECTIVES: To introduce a new implementation of radiomics analysis for cartilage and subchondral bone of the knee and to compare the performance of the proposed models to classic T2 relaxation time in distinguishing knees predisposed to posttraumatic osteoarthritis (PTOA) after anterior cruciate ligament reconstruction (ACLR) and healthy controls. METHODS: 114 patients following ACLR after at least 2 years and 43 healthy controls were reviewed and allocated to training (n = 110) and testing (n = 47) cohorts. Radiomics models are built for cartilage and subchondral bone regions of different compartments: lateral femur (LF), lateral tibia (LT), medial femur (MF), and medial tibia (MT) and combined models of four compartments on T2 mapping images. The model performance of discrimination between patients and controls was illustrated with the receiver operating characteristic curve and compared with a classic T2 value-based model. RESULTS: The T2 value model of cartilage yielded moderate predictive performance in discerning patients and controls, with an AUC of 0.731 (95% confidence interval, 0.556-0.875) in the testing cohort, while the radiomics signature of cartilage and subchondral bone of different compartments demonstrated excellent performance, with AUCs of 0.864-0.979. Furthermore, the combined model reported an even better performance, with AUCs of 0.977 (95% confidence interval, 0.919-1.000) for the cartilage and 0.934 (95% confidence interval, 0.865-0.994) for the subchondral bone in the testing cohort. CONCLUSION: The radiomics features of the cartilage and subchondral bone may be able to provide powerful tools with more sensitive detection than T2 values in differentiating knees at risk for PTOA after ACLR from healthy knees.

Toll-like receptors (TLRs) are the important mediators of inflammatory pathways in the gut which play a major role in mediating the immune responses towards a wide variety of pathogen-derived ligands and link adaptive immunity with the innate immunity. Numerous studies in different populations across the continents have reported on the significant roles of TLR gene polymorphisms in modulating the risk of colorectal cancer (CRC). CRC is one of the major malignancies affecting the worldwide population and is currently ranking the third most common cancer in the world. In this review, we have attempted to discuss the structure, functions, and signaling of TLRs in comprehensive detail together with the role played by various TLR gene SNPs in CRC susceptibility.

OBJECTIVE: The objective of this study was to determine the candidal load of the patients with Chronic Obstructive Pulmonary Disease (COPD) and evaluate the oral health status of subjects with COPD. Material and Methods. N = 112 COPD subjects and N = 100 control subjects were included in the study. The selection of COPD cases was confirmed based on the set criteria from the American College of Physicians. The oral health status was assessed as per WHO criteria to determine the score of decayed, missing, and filled teeth (DMFT), significant caries index (SiC), community periodontal index and treatment needs (CPITN), and oral hygiene index-simplified (OHI-S). Gram staining was performed to identify Candida using the whole saliva. Quantitative evaluation of the candidal load was carried out using Sabouraud Dextrose Agar (SDA). Chrome agar was used to differentiate between the commensal carriages. A statistical analysis paired t-test and 95% confidence interval (CI) for proportions was carried out using STATA software. RESULTS: Candidal growth was found in 21.42% (n = 24) of COPD cases and 1.1% (n = 11) of control cases (p < 0.05) (95% CI 0.45, 0.59). The DMFT score was 8.26 in COPD subjects and 4.6 in controls, the SiC score was 16.42 in COPD subjects and 10.25 in controls, and the CPITN score for both COPD and control cases was score 2. CONCLUSION: In conclusion, there was a higher candidal load among subjects suffering from COPD. Theophylline medication can be a risk factor for increased candidal load in COPD patients.

The present study deals with the evaluation of the age-defying potential of topical cream formulations bearing Geranium essential oil/Calendula essential oil-entrapped ethanolic lipid vesicles (ELVs). Two types of cream formulations were prepared, viz., conventional and ELVs spiked o/w creams. Essential oil- (EO-) loaded ELVs were characterized by vesicle size, polydispersity index, encapsulation efficiency, and scanning electron microscopy. The cream formulations were evaluated for homogeneity, spreadability, viscosity, pH, in vitro antioxidant capacity, sun protection factor, and in vitro collagenase and elastase inhibition capacity. Confocal laser scanning microscopy (CLSM) was performed to ascertain skin permeation of conventional and vesicular cream. The results of in vitro antioxidant studies showed that GEO-/CEO-loaded vesicular creams have notable antioxidant capacity when compared to nonvesicular creams. GEO- or CEO-loaded vesicular creams exhibited the highest SPF value 10.26 and 18.54, respectively. Both the EO-based vesicular creams showed in vitro collagenase and elastase enzyme inhibition capacity. CLSM images clearly depicted that vesicular cream deep into the skin layers. From the research findings, the age-defying potential and photoprotective effects of GEO and CEO were confirmed. It can be concluded that ELVs are able to preserve the efficiency of EOs and have the potential to combat skin aging.

The spread of COVID-19 worldwide continues despite multidimensional efforts to curtail its spread and provide treatment. Efforts to contain the COVID-19 pandemic have triggered partial or full lockdowns across the globe. This paper presents a novel framework that intelligently combines machine learning models and the Internet of Things (IoT) technology specifically to combat COVID-19 in smart cities. The purpose of the study is to promote the interoperability of machine learning algorithms with IoT technology by interacting with a population and its environment to curtail the COVID-19 pandemic. Furthermore, the study also investigates and discusses some solution frameworks, which can generate, capture, store, and analyze data using machine learning algorithms. These algorithms can detect, prevent, and trace the spread of COVID-19 and provide a better understanding of the disease in smart cities. Similarly, the study outlined case studies on the application of machine learning to help fight against COVID-19 in hospitals worldwide. The framework proposed in the study is a comprehensive presentation on the major components needed to integrate the machine learning approach with other AI-based solutions. Finally, the machine learning framework presented in this study has the potential to help national healthcare systems in curtailing the COVID-19 pandemic in smart cities. In addition, the proposed framework is poised as a pointer for generating research interests that would yield outcomes capable of been integrated to form an improved framework.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) can progress to cirrhosis and hepatic carcinoma and is closely associated with changes in the neurological environment. The discovery of new biomarkers would aid in the treatment of NASH. METHODS: Data GSE89632 were downloaded from the Gene Expression Omnibus (GEO) database, and R package "limma" was used to identify differentially expressed genes (DEGs) for NASH vs. normal tissues. The STRING database was used to construct a protein-protein interaction (PPI) network, and the Cytoscape software program (Version 3.80) was used to visualize the PPI network and identify key genes. The immune infiltration of NASH was determined using the R package "CIBERSORT". RESULTS: We screened 41 DEGs. GO and KEGG enrichment analyses of the DEGs revealed the enrichment of pathways related to NAFLD steatosis and inflammation. A PPI network analysis was also performed on the DEGs, and seven genes (MYC, CXCL8, FOS, SOCS1, SOCS3, IL6, and PTGS2) were identified as hub genes. An immune infiltration assessment revealed that macrophages M2, memory resting CD4+ T cells, and γΔ T cells play important roles in the immune microenvironment of NASH, which may be mediated by the seven identified hub genes.

There has been a constant need to develop new and faster cytogenetic assays to measure the instability induced by genotoxic agents in the field of cytogenetic research, an example of which is the micronucleus assay. Micronuclei are fragments or complete chromosomes that remain in the cytoplasm during mitosis. With their high sensitivity and specificity detection, their presence can indicate environmental and occupational genotoxic effects. However, the prolonged periods of cell incubation this assay necessitates are costly and extensive. Hence, it is essential to develop an improved assay that can achieve standardization by being reproducible in practice. The standard protocol for the detection of micronuclei in lymphocytes uses a total assay time of 72 hours. Theoretically, it is possible to reduce the incubation period, and consequently, the total assay time, considering a lymphocyte, completes its mitosis in 24 hours. This study, after careful review of literature, proposes an experimental design to reduce the incubation period and demonstrates its usefulness in practice through the design of a collaborative trial.

BACKGROUND: In emergency hospital settings, rapid diagnosis and isolation of SARS-CoV-2 patients are required. The aim of the study was to evaluate the performance of an antigen chemiluminescence enzymatic immunoassay (CLEIA) and compare it with that of Real-time Reverse transcription-Polymerase Chain Reaction (RT-qPCR), the gold standard assay, to assess its suitability as a rapid diagnostic method for managing patients in the emergency department (ED). METHODS: Consecutive patients with no previous history of SARS-CoV-2 infection attending the ED of the Policlinico Hospital of Bari between 23rd October and 4th November 2020 were enrolled. Clinical and demographic data were collected for all patients. Nasopharyngeal swabs collected on admission were subjected both to molecular (RT-qPCR) and antigen (CLEIA) tests for SARS-CoV-2. The performance of the CLEIA antigen test was analyzed using R Studio software and Microsoft Excel. Receiver operating characteristics were also performed. RESULTS: A total of 911 patients were enrolled, of whom 469 (51.5%) were male. Of the whole cohort, 23.7% tested positive for SARS-CoV-2 by RT-qPCR and 24.5% by CLEIA. The overall concordance rate was 96.8%. The sensitivity, specificity, positive predictive value, and negative predictive value of the antigen test were 94.9% (95% CI, 91.9-97.0), 97.4% (95% CI, 96.5-98.1), 91.9% (95% CI, 89.0-94.0), and 98.4% (95% CI, 97.4-99.1), respectively. The area under the curve (AUC) was 0.99. The kappa coefficient was 0.91. The overall positive and negative likelihood ratios were 37 (95% CI 23-58) and 0.05 (95% CI, 0.03-0.09), respectively. CONCLUSIONS: Data analysis demonstrated that the antigen test showed very good accuracy for discriminating SARS-CoV-2-infected patients from negative participants. The CLEIA is suitable for rapid clinical diagnosis of patients in hospital settings, particularly in EDs with a high prevalence of symptomatic patients and where a rapid turnaround time is critical. Timely and accurate testing for SARS-CoV-2 plays a crucial role in limiting the spread of the virus.

OBJECTIVE: To identify significant pathways and genes in intervertebral disc degeneration (IDD) based on bioinformatics analysis. DESIGN: The GEO database was used to download the GSE124272 dataset. Differentially expressed genes (DEGs) were analyzed using Limma package in R language. Then, gene ontologies (GO), Kyoto encyclopedia of genes and genomes (KEGG), and protein-protein interaction (PPI) networks were used to further identify hub genes. The mRNA expression levels of top six hub genes were verified. RESULTS: We found 563 DEGs, of which 214 were upregulated and 349 were downregulated. The top 5 GO terms and pathways were shown including immune response, cell cycle, and p53 pathway. Based on the PPI analysis, we verified the mRNA expression levels of 6 hub genes. The mRNA levels of CHEK1, CDCA2, SKA3, and KIF20A were upregulated in degenerative NP tissue than in healthy NP tissue. However, the mRNA level of BUB1 and SPC25 was downregulated. CONCLUSIONS: This study may provide new biomarkers for the IDD and treatments to repair IDD related to CHEK1, CDCA2, SKA3, BUB1, KIF20A, and SPC25.

PURPOSE: Circular RNA as a competitive endogenous RNA (ceRNA) plays a significant role in the pathogenesis and progression of breast cancer. In this study, a circular RNA-related ceRNA regulatory network was constructed, which provides new biomarkers and therapeutic targets for the treatment of breast cancer. Materials and methods. The expression profile datasets (GSE101123, GSE143564, GSE50428) of circRNAs, miRNAs, and mRNAs were downloaded from the GEO database, and then differentially expressed RNAs (DEcircRNAs, DEmiRNAs, DEmRNAs) were obtained through the CSCD, TargetScan, miRDB, and miRTarBase databases. CircRNA-miRNA pairs and miRNA-mRNA pairs were constructed. Finally, a ceRNA regulatory network was established. Downstream analysis of the ceRNA network included GO, KEGG analysis, survival analysis, sub-network construction, the BCIP, and qRT-PCR verification. RESULTS: In total, 144 differentially expressed (DE) DEcircRNA, 221 DEmiRNA, and 1211 DEmRNA were obtained, and 96 circRNA-miRNA pairs and 139 miRNA-mRNA pairs were constructed by prediction. The ceRNA regulatory network (circRNA-miRNA-mRNA) was constructed, which included 42 circRNA, 36miRNA, and 78 mRNA. GO function annotation showed genes were mainly enriched in receptor activity activated by transforming growth factor beta (TGF-beta) and in the regulation of epithelial cell apoptosis. KEGG analysis showed genes were mainly enriched in the TGF-beta signaling, PI3K-Akt signaling, and Wnt signaling pathways. Four genes associated with survival and prognosis of breast cancer were obtained by survival analysis, the prognostic sub-network included 4 circRNA, 4 miRNA, and 4 mRNA. BCIP analysis and qRT-PCR verification confirmed that relative mRNA expression levels were consistent with those in the GEO database. CONCLUSION: A circRNA-related ceRNA regulatory network was constructed for breast cancer in this study and key genes affecting pathogenesis and progression were identified. These findings may help better understand and further explore the molecular mechanisms that affect the progression and pathogenesis of breast cancer.

OBJECTIVE: Neuroblastoma (NB) is a highly metastatic tumor in children that develops in the sympathetic nervous system and has a low curative rate. Saikosaponin A (SSA), an active ingredient isolated from the root of Radix Bupleuri, is a natural compound with various pharmacological activities and shows good application prospects in antitumors. This study investigated the antihuman NB activity of SSA and underlying mechanisms associated with its actions. MATERIALS AND METHODS: The MTT method was used to detect the activity of SSA in inhibiting human NB cell SK-N-AS proliferation. Cell morphology was observed. The flow cytometry technology was used in analyzing the cell apoptosis rate. The Transwell assay evaluated cell migration and invasion following SSA treatment, apoptosis-related protein expression, and angiogenesis-related protein expression, and EMT-related proteins were detected by western blot analysis. RESULTS: SSA showed an inhibitory effect on SK-N-AS cells with the IC50 values of 14.14 μM at 24 h and 12.41 μM at 48 h. Results indicated that SSA has proapoptotic activity, and its proapoptotic activity is positively correlated with the Bax/Bcl-2/caspase-9/caspase-7/PARP pathway. Furthermore, SSA inhibited the invasion and migration of SK-N-AS cells via regulating the angiogenesis-related VEGFR2/Src/Akt pathway and the epithelial-mesenchymal transition- (EMT-) related protein expression. CONCLUSION: SSA exerts an antihuman NB effect and thus provides foundations for NB treatment.

METHODS: A total of 121 patients with moderate to severe ARDS admitted to the intensive care unit (ICU) from June 2017 to April 2020 and treated with invasive mechanical ventilation were sequentially included in this study. Their general information was collected, and MP was recorded at 0 h, 24 h, 48 h, and 72 h after admission to the ICU. Professionally trained researchers performed the LUS assessments. Patients were divided into the death and survival groups according to their 28-day prognosis. The trend of MP and LUS at the four time points was analyzed. A receiver operating characteristic curve (ROC) was used to analyze the predictive value of MP and LUS scores at 0 h and 72 h for the prognosis (28-day mortality rate) of patients with moderate to severe ARDS. RESULTS: 121 patients were included in the analysis, of which 73 were male and 48 were female. When patients entered the ICU, their oxygenation index (t: 30885, P < 0.01), APACHE II score (t: 2.105, P < 0.05), and SOFA score (t: 4.134, P < 0.001) were higher in the death group than the survival group. The death group had significantly higher MP and LUS at each time point (0 h, 24 h, 48 h, and 72 h) compared to the survival group (all P < 0.05). There was a significant upward trend over time in the MP and LUS of the death group, contrasting to a significant downward trend in the survival group (all P < 0.05). The Pearson correlation analysis showed that MP and LUS were significantly positively correlated at each time point (r values: 0 h: 0.3027; 24 h: 0.3705; 48 h: 0.3902; 72 h: 0.5916; all P < 0.01). The ROC curves showed that MP and LUS at 72 h were of significant value in predicting the prognosis of ARDS patients, with areas under the curve of 0.866 ± 0.032 and 0.839 ± 0.037, respectively. CONCLUSION: There was a significant correlation between the MP and LUS of ARDS patients at four time points from 0 to 72 h, which has a clinical value in evaluating severity and prognosis.

METHODS: Three models of a single internal connection bone level-type implant inserted into a posterior mandible bone section were constructed using a 3D finite element software: one control model without marginal bone loss and two test models, both with a circumferential peri-implant bone defect, one with a 3 mm high defect and the other one 6 mm high. A 150 N static load was tested on the central fossa at 6° relative to the axial axis of the implant. RESULTS: The results showed differences in the magnitude of strain and stress transferred to the bone between models, being the higher strain found in the trabecular bone around the implant with greater marginal bone loss. Stress distribution differed between models, being concentrated at the cortical bone in the control model and at the trabecular bone in the test models. CONCLUSION: Marginal bone loss around dental implants under occlusal loading influences the magnitude and distribution of the stress transferred and the deformation of peri-implant bone, being higher as the bone loss increases.

The proliferation of pulmonary artery smooth muscle cells (PASMCs) is an important cause of pulmonary vascular remodeling in pulmonary hypertension (PH). It has been reported that miR-137 inhibits the proliferation of tumor cells. However, whether miR-137 is involved in PH remains unclear. In this study, male Sprague-Dawley rats were subjected to 10% O2 for 3 weeks to establish PH, and rat primary PASMCs were treated with hypoxia (3% O2) for 48 h to induce cell proliferation. The effect of miR-137 on PASMC proliferation and calpain-2 expression was assessed by transfecting miR-137 mimic and inhibitor. The effect of calpain-2 on PASMC proliferation was assessed by transfecting calpain-2 siRNA. The present study found for the first time that miR-137 was downregulated in pulmonary arteries of hypoxic PH rats and in hypoxia-treated PASMCs. miR-137 mimic inhibited hypoxia-induced PASMC proliferation and upregulation of calpain-2 expression in PASMCs. Furthermore, miR-137 inhibitor induced the proliferation of PASMCs under normoxia, and knockdown of calpain-2 mRNA by siRNA significantly inhibited hypoxia-induced proliferation of PASMCs. Our study demonstrated that hypoxia-induced downregulation of miR-137 expression promoted the proliferation of PASMCs by targeting calpain-2, thereby potentially resulting in pulmonary vascular remodeling in hypoxic PH.