BACKGROUND: Advances in cancer research have allowed for early diagnosis and improved treatment of cutaneous melanoma (CM). However, its invasiveness and recurrent metastasis, along with rising resistance to newer therapies, have lent urgency to the search for novel biomarkers and the underlying molecular mechanisms of CM. METHODS: Single nucleotide polymorphism- (SNP-) related genes were obtained from the sequencing data of 428 CM samples in The Cancer Genome Atlas. Functional enrichment of these genes was analysed in clusterProfiler. Additionally, a protein-protein interaction (PPI) network was constructed with the Search Tool for the Retrieval of Interacting Gene (STRING) database. Gene Expression Profiling Interactive Analysis (GEPIA) was used to identify the expression and prognostic value of mutated genes. Finally, the Tumour Immune Estimation Resource (TIMER) analysed the relationship between gene expression and immune cell infiltration. RESULTS: We constructed a PPI network from the top 60 SNP-related genes. Mutated genes were mainly involved in calcium and oxytocin signalling pathways, as well as circadian entrainment. In addition, three SNP-related genes, BRAF, FLG, and SORL1, were significantly associated with patient prognosis. BRAF and SORL1 were positively associated with infiltration abundance of B cells, CD8+ T cells, CD4+ T cells, neutrophils, and dendritic cells, whereas FLG expression was negatively associated. Furthermore, higher immune cell infiltration was positively correlated with good prognosis. CONCLUSIONS: Our study provides vital bioinformatic data and a relevant theoretical basis to further explore the molecular pathogenesis of CM and improve patient prognosis.

The hepatitis B virus (HBV) is one of the major viral infection problems worldwide in public health. The exclusive proprietary Chinese medicine Ganweikang (GWK) tablet has been marketed for years in the treatment of chronic hepatitis B (CHB). However, the pharmacodynamic material basis and underlying mechanism of GWK are not completely clear. This study is aimed at investigating the pharmacological mechanism of the GWK tablet in the treatment of CHB. The chemical ingredient information was obtained from the Traditional Chinese Medicine Database and Analysis Platform (TCMSP), Traditional Chinese Medicines Integrated Database (TCMID), and Shanghai Institute of Organic Chemistry of CAS. Ingredients and disease-related targets were defined by a combination of differentially expressed genes from CHB transcriptome data and open-source databases. Target-pathway-target (TPT) network analysis, molecular docking, and chemical composition analysis were adopted to further verify the key targets and corresponding active ingredients of GWK. Eight herbs of GWK were correlated to 330 compounds with positive oral bioavailability, and 199 correlated targets were identified. The TPT network was constructed based on the 146 enriched targets by KEGG pathway analysis, significantly associated with 95 pathways. Twenty-five nonvolatile components and 25 volatile components in GWK were identified in UPLC-QTOF/MS and GC-MS chromatograms. The key active ingredients of GWK include ferulic acid, oleanolic acid, ursolic acid, tormentic acid, 11-deoxyglycyrrhetic acid, dibenzoyl methane, anisaldehyde, wogonin, protocatechuic acid, psoralen, caffeate, dimethylcaffeic acid, vanillin, β-amyrenyl acetate, formonentin, aristololactam IIIa, and 7-methoxy-2-methyl isoflavone, associated with targets CA2, NFKB1, RELA, AKT1, JUN, CA1, CA6, IKBKG, FOS, EP300, CREB1, STAT1, MMP9, CDK2, ABCB1, and ABCG2.

Considering the unique properties of magnesium and its alloy, it has a vast demand in biomedical applications, particularly the implant material in tissue engineering due to its biodegradability. But the fixing spares must hold such implants till the end of the biodegradation of implant material. The composite technology will offer the added benefits of altering the material properties to match the requirements of the desired applications. Hence, this experimental investigation is aimed at developing a composite material for manufacturing fixing spares like a screw for implants in biomedical applications. The matrix of AZ63 magnesium alloy is reinforced with nanoparticles of zirconium (Zr) and titanium (Ti) through the stir casting-type synthesis method. The samples were prepared with equal contributions of zirconium (Zr) and titanium (Ti) nanoparticles in the total reinforcement percentage (3%, 6%, 9%, and 12%). The corrosive and tribological studies were done. In the corrosive study, the process parameters like NaCl concentration, pH value, and exposure time were varied at three levels. In the wear study, the applied Load, speed of sliding, and the distance of the slide were considered at four levels. Taguchi analysis was employed in this investigation to optimize the reinforcement and independent factors to minimize the wear and corrosive losses. The minimum wear rate was achieved in the 12% reinforced sample with the input factor levels of 60 N of load on the pin, 1 m/s of disc speed at a sliding distance was 1500 m, and the 12% reinforce samples also recorded a minimum corrosive rate of 0.0076 mm/year at the operating environment of 5% NaCl-concentrated solution with the pH value of 9 for 24 hrs of exposure. The prediction model was developed based on the experimental results.

The virus responsible for the coronavirus viral pandemic is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Emerging SARS-CoV-2 variants caused by distinctive mutations within the viral spike glycoprotein of SARS-CoV-2 are considered the cause for the rapid spread of the disease and make it challenging to treat SARS-CoV-2. The manufacturing of appropriate efficient vaccines and therapeutics is the only option to combat this pandemic. Nanomedicine has enabled the delivery of nucleic acids and protein-based vaccines to antigen-presenting cells to produce protective immunity against the coronavirus. Nucleic acid-based vaccines, particularly mRNA nanotechnology vaccines, are the best prevention option against the SARS-CoV-2 pandemic worldwide, and they are effective against the novel coronavirus and its multiple variants. This review will report on progress made thus far with SARS-CoV-2 vaccines and beyond employing nanotechnology-based nucleic acid vaccine approaches.

Mosquitoes present an immense threat to millions of people worldwide and act as vectors for filariasis disease. The objective of the study was to determine the effect of Allium sativum and Zingiber officinale extracts against filariasis vectors. The larvae were collected from the breeding site by using standard procedures for identification and larvicidal activities. Twenty grams (20 g) from each (Allium sativum and Zingiber officinale) were extracted separately by aqueous, ethanol, and methanol solvents. The phytochemical analysis was determined in the crude sample by using standard methods. Then, larvicidal effects were determined by introducing 10 larvae of the vectors to the concentrations of 250 ppm, 500 ppm, and 750 ppm of the crude sample, and data were subjected to probit analysis to determine the LC50 and Chi-squared test to check the significance of the mortality by R software. Anopheles funestus, Anopheles gambiae s.l., Anopheles pharoensis, Culex antennatus, and Culex quinquefasciatus were the filariasis vectors identified during the study period. The presence of phytochemical tests such as anthraquinones, flavonoids, glycosides, phenol, saponin, steroids, tannin, and terpenes was obtained. The larvicidal effects of the selected plant extracts ranged from 0%-100%. The lowest LC50 (53 ppm) was observed for A. sativum methanol test extract against Cx. quinquefasciatus. Ethanol extracts of A. sativum have a significant effect on An. funestus (X2 = 7.5, p = 0.02352) and Cx. quinquefasciatus (X2 = 10.833, p = 0.0.0044), whereas aqueous extracts have a significant effect only on An. gambiae s.l. (X2 = 7.0807, p = 0.029. Ethanol extracts of Z. officinale have a significant effect only on the mortality of An. pharoensis (X2 = 7.0807, p = 0.029), but methanol and aqueous extracts have no significant effect against filariasis vectors. In conclusion, A. sativum have a high toxic effect than Z. officinale extract against filariasis vectors in all type of solvents. So using those plant extracts is the best to reduce the risk of the synthetic chemical on nontarget organisms and the environment, in addition to the control of mosquito-borne diseases, but further studies will be conducted to evaluate the toxicity at different stages of the vectors.

BACKGROUND: Nowadays, due to various inherent properties, graphene-based nanoparticles are widely used in drug delivery research. On the other hand, folate receptors are highly expressed on the surface of human tumor cells. In this work, to enhance the 5-fluorouracil (5FU) and curcumin (Cur) effects on colon cancer, we constructed a folic acid- (FA-) modified codelivery carrier based on graphene nanoparticles (GO-Alb-Cur-FA-5FU). MATERIALS AND METHODS: The HUVEC and HT-29 were selected for evaluating the antitumor effect of the prepared nanocarriers. The structure of nanocarriers was characterized by FTIR spectroscopy, X-ray diffraction analysis, TEM microscopy, and a DLS analyzer. The efficiency of the prepared carrier was evaluated by fluorescence microscopy using Annexin V and the PI kit. The cytotoxicity of the carrier's component individually and the efficacy of the drug carrier GO-Alb-Cur-FA-5FU were assessed by MTT. RESULTS: The results of the pharmacological tests indicated that the new nanoparticles cause increased apparent toxicity in HT-29 cells. The apoptosis rate of the HT-29 and HUVEC cells treated with IC50 values of GO-Alb-Cur-FA-5FU for 48 h was higher than the cells treated with IC50 values of 5FU and Cur individually, which indicated the greater inhibitory efficacy of GO-Alb-Cur-FA-5FU than free drugs. CONCLUSION: The designed GO-Alb-CUR-FA-5FU delivery system can be applied for targeting colon cancer cells and can be severe as a potential candidate for future drug development.

The Sahara Desert, one of the most extreme ecosystems in the planet, constitutes an unexplored source of microorganisms such as mycelial bacteria. In this study, we investigated the diversity of halophilic actinobacteria in soils collected from five regions of the Algerian Sahara. A total of 23 halophilic actinobacterial strains were isolated by using a humic-vitamin agar medium supplemented with 10% NaCl. The isolated halophilic strains were subjected to taxonomic analysis using a polyphasic approach, which included morphological, chemotaxonomic, physiological (numerical taxonomy), and phylogenetic analyses. The isolates showed abundant growth in CMA (complex medium agar) and TSA (tryptic soy agar) media containing 10% NaCl, and chemotaxonomic characteristics were consistent with their assignment to the genus Nocardiopsis. Analysis of the 16S rRNA sequence of 23 isolates showed five distinct clusters and a similarity level ranging between 98.4% and 99.8% within the Nocardiopsis species. Comparison of their physiological characteristics with the nearest species showed significant differences with the closely related species. Halophilic Nocardiopsis isolated from Algerian Sahara soil represents a distinct phyletic line suggesting a potential new species. Furthermore, the isolated strains of halophilic Nocardiopsis were screened for their antagonistic properties against a broad spectrum of microorganisms by the conventional agar method (agar cylinders method) and found to have the capacity to produce bioactive secondary metabolites. Except one isolate (AH37), all isolated Nocardiopsis showed moderate to high biological activities against Pseudomonas syringae and Salmonella enterica, and some isolates showed activities against Agrobacterium tumefaciens, Serratia marcescens, and Klebsiella pneumoniae. However, no isolates were active against Bacillus subtilis, Aspergillus flavus, or Aspergillus niger. The obtained finding implies that the unexplored extreme environments such as the Sahara contain many new bacterial species as a novel drug source for medical and industrial applications.

In Cameroon, malaria is still the cause of several deaths yearly and leading to the continued search for new potent leads to fight against Plasmodium falciparum. Medicinal plants like Hypericum lanceolatum Lam. are introduced in local preparations for the treatment of affected people. The bioassay-guided fractionation of the crude extract of the twigs and stem bark of H. lanceolatum Lam. led to the identification of the dichloromethane-soluble fraction as the most active (with 32.6% of the parasite P. falciparum 3D7 survival) which was further purified by successive column chromatography to obtain four compounds identified by their spectrometric data as two xanthones 1,6-dihydroxyxanthone (1) and norathyriol (2) and two triterpenes betulinic acid (3) and ursolic acid (4). In the antiplasmodial assay against P. falciparum 3D7, the triterpenoids 3 and 4 displayed the most significant potencies with IC50 values of 2.8 ± 0.8 μg/mL and 11.8 ± 3.2 μg/mL, respectively. Furthermore, both compounds were also the most cytotoxic against P388 cell lines with IC50 values of 6.8 ± 2.2 μg/mL and 2.5 ± 0.6 μg/mL, respectively. Further insights on the inhibition method of the bioactive compounds and their drug-likeness were obtained from their molecular docking and ADMET studies. The results obtained help in identifying additional antiplasmodial agents from H. lanceolatum and support its use in folk medicine for the treatment of malaria. The plant might be considered as a promising source of new antiplasmodial candidates in new drug discovery.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by dementia as the primary clinical symptom. The production and accumulation of aggregated β-amyloid (Aβ) in patient brain tissues is one of the hallmarks of AD pathogenesis. Microglia, brain-resident macrophages, produce inflammatory cytokines in response to Aβ oligomers or fibrils exacerbating Aβ pathology in AD. HMO6 cells were treated with Aβ42 in the presence or absence of 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) to determine its potential immunomodulatory effects, and the expression of pro-/anti-inflammatory cytokines, M1/M2-associated markers, Toll-like receptors (TLRs), and triggering receptor expressed on myeloid cells 2 (TREM2) was examined. 1,25(OH)2D3 was found to suppress Aβ-induced expression of proinflammatory cytokines (TNF-α, IL-1β, and IL-6), M1 markers (CD86 and iNOS), and TLR2/4, whilst increasing the expression of anti-inflammatory cytokines (IL-4, IL-10, and CCL17) and M2 markers (CD206 and Arg-1). Furthermore, 1,25(OH)2D3 promoted TREM2 expression and Aβ uptake by HMO6 cells, and the enhancement of Aβ uptake and M2 polarization was revealed to be TREM2-dependent. The findings of this study suggest that 1,25(OH)2D3 facilitates M2 polarization and Aβ uptake in a TREM2-dependent manner.

Pathophysiologically, type 2 diabetes can result from insulin resistance or insulin insufficiency alone. It is unclear whether relative insulin shortage or pronounced insulin resistance is linked to poor cardiometabolic problems like obesity. Therefore, the objective of this study was to evaluate the relationship between insulin resistance (IR), hypertension, and dyslipidaemia, in men with type 2 diabetes mellitus. One hundred and twenty-one (121) type 2 diabetic men participated in this cross-sectional study, which was conducted between September 2018 and September 2019. Sociodemographic information was collected using a self-designed questionnaire. Anthropometric data were also taken and blood samples collected for estimation of insulin, glucose, and lipid concentrations. HOMA-IR was calculated from the fasting insulin and glucose values, and a HOMA - IR ≥ 2 was considered to indicate insulin resistance. Of the 121 participants, 39.7% were classified as insulin-resistant. Levels of total cholesterol (4.82 ± 1.2 mmol/L; p = 0.007 vs. 4.25 ± 1.1 mmol/L), LDL cholesterol (3.17 ± 0.9 mmol/L; p = 0.001 vs. 2.52 ± 0.8 mmol/L), and TC/HDL-C ratio (3.93 ± 0.9; p = 0.042 vs. 3.58 ± 0.9) and the prevalence of abnormal LDL-C (14.6%; p = 0.015 vs. 2.7%) and elevated BP (83.3%; p = 0.048 vs. 67.1%) were higher in the insulin-resistant group. LDL cholesterol (AUC = 0.670; p = 0.001) better classified subjects as being insulin-resistant compared to other lipid markers. The odds of insulin resistance in dyslipidaemia were not statistically significant after adjusting for obesity. The link between insulin resistance and dyslipidaemia and hypertension in male diabetics may thus be mediated by obesity.

BACKGROUND: The multiple forms of malnutrition, including overnutrition, undernutrition, and diet-related noncommunicable diseases, are emerging crises in Asian countries. Past studies have focused more on malnutrition among overweight/obese individuals; however, limited research has examined chronic energy-deficient adults. Therefore, this study is aimed at investigating the prevalence and determinants of different forms of malnutrition among adults with different body mass index, using the Philippines as an example. Findings from this study will guide the development and implementation of public health nutrition programs and policies. METHODS: A representative dataset from the 2013 Philippine National Nutrition Survey was used in the study. Adults aged ≥20 years (n = 16,826) were included in the analysis after excluding those with missing values. Six phenotypes of malnutrition were assessed, including three in overweight/obese adults (overweight/obese with metabolic syndrome; those with micronutrient deficiency-anemia, vitamin A deficiency, and iodine insufficiency; and those with both metabolic syndrome and micronutrient deficiency) and three in chronic energy-deficient (CED) adults (CED with either metabolic syndrome or micronutrient deficiency and with both metabolic syndrome and micronutrient deficiency). Sociodemographic and lifestyle factors were examined as the determinants of different forms of malnutrition, and multinomial logistic regression analyses were performed. RESULTS: The prevalence of the six phenotypes of malnutrition ranged from 0.4% to 10.2%, where overweight/obese with metabolic syndrome was the most predominant type. The multinomial logistic regression models indicated that older age was the major risk factor across all phenotypes. Sex was associated with the outcomes in the overweight/obesity group, whereas employment status was correlated with CED adults. Furthermore, higher educational levels, being married, living in affluent households, and not smoking were protective factors for conditions related to CED but not overweight/obese individuals. CONCLUSION: Malnutrition in all its forms is a significant public health concern that must be understood and addressed. Policymakers should implement appropriate intervention programs to control these nutritional problems considering the specific risk factors for the adult population.

BACKGROUND: In the present work, we investigated the effect of exogenous glutathione in old rats on the expression of ATP-sensitive potassium (KATP) channels, the mitochondrial permeability transition pore (mPTP) opening in the heart, and the vasorelaxation responses of isolated aortic rings to activation of KATP channels. METHODS: Experiments were performed on adult (6 months) and old (24 months) male Wistar rats, which were divided into three groups: adult, old, and glutathione-treated old rats. Glutathione was injected intraperitoneally at a dose of 52 mg/kg 1 hour before the studies. The mRNA expression of KATP channels was determined using reverse transcription and real-time polymerase chain reaction analysis. The effect of glutathione administration on mPTP opening, relaxation responses of isolated aortic rings, and oxidative stress markers was studied. RESULTS: It was shown that the expression levels of Kir6.1, Kir6.2, and SUR1 subunits of KATP channels and levels of reduced glutathione were significantly increased in glutathione-treated old rats (by 8.3, 2.8, 13.1, and 1.5-fold, respectively), whereas the levels of oxidative stress markers (hydrogen peroxide, diene conjugates, malondialdehyde, and rate of superoxide generation) in heart mitochondria and mPTP opening were significantly reduced. Relaxation of aortic rings was significantly increased in response to the actions of KATP channel openers flocalin and pinacidil in glutathione-treated animals, which was prevented by glibenclamide. CONCLUSIONS: Thus, the administration of exogenous glutathione to old rats resulted in a significant increase in the expression levels of the Kir6.1, Kir6.2, and SUR1 subunits of KATP channels and a decrease in oxidative stress. This was accompanied by inhibition of mPTP opening and enhancement of vasorelaxation responses to activation of KATP channels.

Lactoferrin (LF) is a major natural antimicrobial agent secreted in body fluids as a natural innate immunity protein. The action and structure of LF are closely related to its iron-binding capacity with structural reporting in open and closed conformations. This study looked at how lactoferrin structures change in camel (cLF), bovine (bLF), and human (hLF) lactoferrin closed forms after iron is removed from their binding sites. Initially, the sequence comparison between cLF and the LFs of marine mammals, bats, and domestic animals was the most intriguing conclusion. Camel LF is revealed to be more closely related to marine animals (~80.36% identity) and bats (~79.3% identity) than to terrestrial mammal species (~75.5% identity). Results indicated that cLF was more dynamic in nature than bLF and hLF by showing higher RMSD values. The cLF is known to be half lactoferrin half transferrin; in this study, we show that there are different MD behavior of both iron-binding sites. While LF contains two lobes (C- and N-lobes), the C-lobe showed high fluctuations as N-lobe was more stable in the absence of ferric ions. The C-lobe and N-lobe of cLF react differently at physiological pH, revealing distinct molecular interactions between these components. In addition, cLF showed higher system flexibility derived from its larger RMSD, RMSF, lower intermolecular hydrogen bonds, and higher solvent accessible surface area (SASA).

Angiogenesis is crucial to the development of cancer because it allows the transport of oxygen, nutrients, and growth factors as well as the spread of tumors to distant organs. Inhibitors of angiogenesis prevent the formation of blood vessels that allow tumor cells to shrink, rather than promote tumor growth. Chitosan acts as a carrier for many drugs, since the compound has various properties such as biodegradable, less toxicity, more stable, simple, easy to prepare, and biocompatible. The aim of the current study was to evaluate the efficacy of chitosan nanoparticles encapsulated with troxerutin (Chi-Trox NPs) against angiogenesis and cancer in ova chick chorioallantoic membrane (CAM) model. Chi-Trox NPs were synthesized using a nanoprecipitation method and were characterized by various analyses. 24 hours' fertilized eggs (6 eggs/group) were treated with native Trox and Chi-Trox NPs for 5 days. The antiangiogenic activity was evaluated by morphometric, histopathological, immunohistochemical (CD104 and vimentin), and mRNA expression of MMP and FGF2 using RT-PCR. The anticancer activity was evaluated by histopathological, immunohistochmical (CD44), and mRNA expression of FGF2 and MMP. The synthesized chitosan NPs were successfully encapsulated with troxerutin, and the loading efficiency of chitosan NPs was found to be 86.4 ± 0.12% and 13.2 ± 0.16% respectively. Morphometric analysis of Chi-Trox NPs showed a considerable decrease in the number of blood vessels compared with control and native Trox. The histopathological observation of CAM confirmed that Chi-Trox NPs induce a significant reduction in inflammatory cells and the thickness of blood capillaries compared to control and native Trox. The immunohistochemical evaluation of CAM revealed Chi-Trox decreased CD104, vimentin and CD44 protein levels were compared with control and native Trox. Furthermore, the mRNA expression levels of FGF2 and MMP were significantly downregulated compared to their native forms. From the obtained results, Chi-Trox NPs possess significant inhibition of angiogenesis and can be used as therapeutic agents for cancer in the future.

Multidrug-resistant (MDR) pathogens have created a fatal problem for human health and antimicrobial treatment. Among the currently available antibiotics, many are inactive against MDR pathogens. In this context, heterocyclic compounds/drugs play a vital role. Thus, it is very much essential to explore new research to combat the issue. Of the available nitrogen-bearing heterocyclic compounds/drugs, pyridine derivatives are of special interest due to their solubility. Encouragingly, some of the newly synthesized pyridine compounds/drugs are found to inhibit multidrug-resistant S. aureus (MRSA). Pyridine scaffold bearing poor basicity generally improves water solubility in pharmaceutically potential molecules and has led to the discovery of numerous broad-spectrum therapeutic agents. Keeping these in mind, we have reviewed the chemistry, recent synthetic techniques, and bacterial preventative activity of pyridine derivatives since 2015. This will facilitate the development of pyridine-based novel antibiotic/drug design in the near future as a versatile scaffold with limited side effects for the next-generation therapeutics.

Methicillin-resistant Staphylococcus aureus (MRSA) has evolved resistance even against the last resort β-lactam antibiotics. This is because of the acquisition of an additional penicillin-binding protein 2a (PBP2a) which is a resistance determinant in MRSA. Currently, available PBP2a inhibitors are ineffective against life-threatening and fatal infections caused by microorganisms. Therefore, there is an urgent need to screen natural compounds that could overpass the resistance issue alone or in combination with antibacterial drugs. We studied the interactions of different phytochemicals with PBP2a so that crosslinking of peptidoglycans could be inhibited. In structure-based drug designing, in silico approach plays a key role in determining phytochemical interactions with PBP2a. In this study, a total of 284 antimicrobial phytochemicals were screened using the molecular docking approach. The binding affinity of methicillin, -11.241 kcal/mol, was used as the threshold value. The phytochemicals having binding affinities with PBP2a stronger than methicillin were identified, and the drug-likeness properties and toxicities of the screened phytochemicals were calculated. Out of the multiple phytochemicals screened, nine were found as good inhibitors to be PBP2a, among which cyanidin, tetrandrine, cyclomorusin, lipomycin, and morusin showed strong binding potential with the receptor protein. These best-selected phytochemicals were also docked to the allosteric site of PBP2a, and most of the compounds revealed strong interactions with the allosteric site. These compounds were safe to be used as drugs because they did not show any toxicity and had good bioactivity scores. Cyanidin had the highest binding affinity (S-score of -16.061 kcal/mol) with PBP2a and with high gastrointestinal (GI) absorption. Our findings suggest that cyanidin can be used as a drug against MRSA infection either in purified form or that its structure can lead to the development of more potent anti-MRSA medicines. However, experimental studies are required to evaluate the inhibitory potential of these phytochemicals against MRSA.

BACKGROUND: The youth in Uganda, as in much of sub-Saharan Africa, face numerous sexual and reproductive health (SRH) challenges, from human immunodeficiency virus HIV infection, and unsafe abortions to unwanted pregnancies. This study, therefore, assessed the utilization of sexual and reproductive health services and associated factors among the youth in Lira city west, northern Uganda. METHODS: This was a cross-sectional study conducted in January 2023 among 386 young people (15-24 years) in Lira city west division, Lira city. Multistage cluster sampling technique was used to recruit our study participants. Data were collected using an interviewer-administered questionnaire. Data were analyzed using SPSS version 23, descriptive statistics, cross-tabulation, bivariate, and multivariate logistic regression analyses. All variables were set by p values less than 0.05 and reported adjusted odds ratio with its 95% confidence interval. RESULTS: The utilization of SRH services was 42.0% (162/386) among the study participants. Family planning, voluntary HIV counseling and testing (VCT), and general counseling services were the most utilized SRH services in the past 12 months. Young people who were aware of SRH services (AOR: 0.24; 95% CI: 0.08-0.74), were aware of a reproductive health facility (AOR, 4.24; 95% CI: 1.62-11.09), discussed SRH issues with peers/friends (AOR, 3.98; 95% CI: 1.53-10.33), had a sexual partner (AOR, 10.00; 95% CI: 4.05-24.69), had sexual intercourse (AOR, 4.59; 95% CI: 2.18-9.69), and had access to SRH services (AOR, 2.68; 95% CI: 1.12-6.40) were more likely to utilize SRH services compared to their counterparts. CONCLUSION: This study showed a low utilization of sexual and reproductive health services among youth in Lira city west, northern Uganda. Being aware of SRH services, awareness of reproductive health facilities, discussing SRH issues with peers, having sexual intercourse, having a sexual partner, and access to SRH services were independently associated with the utilization of SRH services. Therefore, there is a need to strengthen sustainable multisector approaches aimed at improving awareness and access to sexual and reproductive health services among the youth.

Artificial intelligence (AI) scholars and mediciners have reported AI systems that accurately detect medical imaging and COVID-19 in chest images. However, the robustness of these models remains unclear for the segmentation of images with nonuniform density distribution or the multiphase target. The most representative one is the Chan-Vese (CV) image segmentation model. In this paper, we demonstrate that the recent level set (LV) model has excellent performance on the detection of target characteristics from medical imaging relying on the filtering variational method based on the global medical pathology facture. We observe that the capability of the filtering variational method to obtain image feature quality is better than other LV models. This research reveals a far-reaching problem in medical-imaging AI knowledge detection. In addition, from the analysis of experimental results, the algorithm proposed in this paper has a good effect on detecting the lung region feature information of COVID-19 images and also proves that the algorithm has good adaptability in processing different images. These findings demonstrate that the proposed LV method should be seen as an effective clinically adjunctive method using machine-learning healthcare models.

Previous studies reported a relationship between thyroid-stimulating hormone (TSH) and low-density lipoprotein cholesterol (LDL-C) levels. In this study, we aim to evaluate the impact of TSH levels on lipid profile in patients with familial hypercholesterolemia (FH) and euthyroid state. Patients were selected from the Isfahan FH registry. The Dutch Lipid Clinic Network (DLCN) criteria are used to detect FH. Patients were classified into no FH, possible FH, probable FH, and definite FH groups based on the DLCN scores. Patients with any cause of secondary hyperlipidemia, including hypothyroidism, were excluded from this study. The study group consisted of 103 patients with possible FH, 25 patients with definite FH, and 63 individuals with no FH. The mean TSH and LDL-C levels among participants were 2.10 ± 1.22 mU/l and 142.17 ± 62.56 mg/dl, respectively. No positive or negative correlation was found between serum TSH and total cholesterol (P value = 0.438), high-density lipoprotein cholesterol (P = 0.225), triglycerides (P value = 0.863), and LDL-C (P value = 0.203). We found no correlation between serum TSH levels and lipid profiles in euthyroid patients with FH.

Staphylococci can cause urinary tract infections (UTIs). These UTIs are among the significant causes of antibiotic resistance and the spread of antibiotic-resistant diseases. The current study is aimed at establishing a resistance profile and determining the pathogenicity of Staphylococcus strains isolated from UTI samples collected in Benin. For this purpose, urine samples (one hundred and seventy) that were collected from clinics and hospitals showed UTI in patients admitted/visited in Benin. The biochemical assay method was used to identify Staphylococcus spp., and the disk diffusion method tested the antimicrobial susceptibility. The biofilm formation ability of the isolates of Staphylococcus spp. was investigated by the colorimetric method. The presence of mecA, edinB, edinC, cna, bbp, and ebp genes was examined by multiplex polymerase chain reaction (PCR). The results showed that Staphylococcus species were identified in 15.29% of all infected individuals and that 58% of these strains formed biofilms. Most Staphylococcus strains (80.76%) were isolated in female samples, and the age group below 30 years appeared to be the most affected, with a rate of 50%. All Staphylococcus strains isolated were 100% resistant to penicillin and oxacillin. The lowest resistance rates were seen with ciprofloxacin (30.8%), gentamicin, and amikacin (26.90%). Amikacin was the best antibiotic against Staphylococcus strains isolated from UTIs. The isolates carried mecA (42.31%), bbp (19.23%), and ebp (26.92%) genes in varying proportions. This study provides new information on the risks posed to the population by the overuse of antibiotics. In addition, it will play an essential role in restoring people's public health and controlling the spread of antibiotic resistance in urinary tract infections in Benin.

BACKGROUND: A comparison of emergency residents' judgments and two derivatives of the Sequential Organ Failure Assessment (SOFA), namely, the mSOFA and the qSOFA, was conducted to determine the accuracy of predicting in-hospital mortality among critically ill patients in the emergency department (ED). METHODS: A prospective cohort research was performed on patients over 18 years of age presented to the ED. We used logistic regression to develop a model for predicting in-hospital mortality by using qSOFA, mSOFA, and residents' judgment scores. We compared the accuracy of prognostic models and residents' judgment in terms of the overall accuracy of the predicted probabilities (Brier score), discrimination (area under the ROC curve), and calibration (calibration graph). Analyses were carried out using R software version R-4.2.0. RESULTS: In the study, 2,205 patients with median age of 64 (IQR: 50-77) years were included. There were no significant differences between the qSOFA (AUC 0.70; 95% CI: 0.67-0.73) and physician's judgment (AUC 0.68; 0.65-0.71). Despite this, the discrimination of mSOFA (AUC 0.74; 0.71-0.77) was significantly higher than that of the qSOFA and residents' judgments. Additionally, the AUC-PR of mSOFA, qSOFA, and emergency resident's judgments was 0.45 (0.43-0.47), 0.38 (0.36-0.40), and 0.35 (0.33-0.37), respectively. The mSOFA appears stronger in terms of overall performance: 0.13 vs. 0.14 and 0.15. All three models showed good calibration. CONCLUSION: The performance of emergency residents' judgment and the qSOFA was the same in predicting in-hospital mortality. However, the mSOFA predicted better-calibrated mortality risk. Large-scale studies should be conducted to determine the utility of these models.

SARS-CoV-2, a deadly coronavirus sparked COVID-19 pandemic around the globe. With an increased mutation rate, this infectious agent is highly transmissible inducing an escalated rate of infections and death everywhere. Hence, the discovery of a viable antiviral therapy option is urgent. Computational approaches have offered a revolutionary framework to identify novel antimicrobial treatment regimens and allow a quicker, cost-effective, and productive conversion into the health center by evaluating preliminary and safety investigations. The primary purpose of this research was to find plausible plant-derived antiviral small molecules to halt the viral entrance into individuals by clogging the adherence of Spike protein with human ACE2 receptor and to suppress their genome replication by obstructing the activity of Nsp3 (Nonstructural protein 3) and 3CLpro (main protease). An in-house library of 1163 phytochemicals were selected from the NPASS and PubChem databases for downstream analysis. Preliminary analysis with SwissADME and pkCSM revealed 149 finest small molecules from the large dataset. Virtual screening using the molecular docking scoring and the MM-GBSA data analysis revealed that three candidate ligands CHEMBL503 (Lovastatin), CHEMBL490355 (Sulfuretin), and CHEMBL4216332 (Grayanoside A) successfully formed docked complex within the active site of human ACE2 receptor, Nsp3, and 3CLpro, respectively. Dual method molecular dynamics (MD) simulation and post-MD MM-GBSA further confirmed efficient binding and stable interaction between the ligands and target proteins. Furthermore, biological activity spectra and molecular target analysis revealed that all three preselected phytochemicals were biologically active and safe for human use. Throughout the adopted methodology, all three therapeutic candidates significantly outperformed the control drugs (Molnupiravir and Paxlovid). Finally, our research implies that these SARS-CoV-2 protein antagonists might be viable therapeutic options. At the same time, enough wet lab evaluations would be needed to ensure the therapeutic potency of the recommended drug candidates for SARS-CoV-2.

This study is aimed at investigating the potential molecular features of allergic rhinitis (AR) and identifying gene signatures and related transcription factors using transcriptome analysis and in silico datasets. Transcriptome profiles were obtained using three independent cohorts (GSE101720, GSE19190, and GSE46171) comprising healthy controls (HC) and patients with AR. The pooled dataset (n = 82) was used to identify the critical signatures of AR compared with HC. Subsequently, key transcription factors were identified by a combined analysis using transcriptome and in silico datasets. Gene ontology: bioprocess (GO: BP) analysis using differentially expressed genes (DEGs) revealed that immune response-related genes were significantly enriched in AR compared with HC. Among them, IL1RL1, CD274, and CD44 were significantly higher in AR patients. We also identified key transcription factors between HC and AR using the in silico dataset and found that AR samples frequently express KLF transcription factor 4 (KLF4), which regulates immune response-related genes including IL1RL1, CD274, and CD44 in human nasal epithelial cells. Our integrative analysis of transcriptomic regulation provides new insights into AR, which may help in developing precision management for patients with AR.