Since insulin deficiency results from pancreatic beta-cell destruction, all type 1 and most type 2 diabetes patients eventually require life-long insulin injections. Insulin gene synthesis could also be impaired due to insulin gene mutations as observed in diabetic patients with MODY 10. At this point, insulin gene therapy could be very effective to recompense insulin deficiency under these circumstances. For this reason, an HIV-based lentiviral vector carrying the insulin gene under the control of insulin promoter (LentiINS) was generated, and its therapeutic efficacy was tested in a beta-cell transplant model lacking insulin produced by CRISPR/Cas9-mediated genetically engineered pancreatic beta cells. To generate an insulin knockout beta-cell transplant animal model of diabetes, a dual gene knockout plasmid system involving CRISPR/Cas9 was transfected into a mouse pancreatic beta cell line (Min6). Fluorescence microscopy and antibiotic selection were utilized to select the insulin gene knockout clones. Transplantation of the genetically engineered pancreatic beta cells under the kidney capsule of STZ-induced diabetic rats revealed LentiINS- but not LentiLacZ-infected Ins2KO cells transiently reduced hyperglycemia similar to that of MIN6 in diabetic animals. These results suggest LentiINS has the potential to functionally restore insulin production in an insulin knockout beta-cell transplant animal model of diabetes.

Drug resistance in leukaemia is a major problem that needs to be addressed. Precision medicine provides an avenue to reduce drug resistance through a personalised treatment plan. It has helped to better stratify patients based on their molecular profile and therefore improved the sensitivity of patients to a given therapeutic regimen. However, therapeutic options are still limited for patients who have already been subjected to many lines of chemotherapy. The process of designing and developing new drugs requires significant resources, including money and time. Drug repurposing has been explored as an alternative to identify effective drug(s) that could be used to target leukaemia and lessen the burden of drug resistance. The drug repurposing process usually includes preclinical studies with drug screening and clinical trials before approval. Although most of the repurposed drugs that have been identified are generally safe for leukaemia treatment, they seem not to be good candidates for monotherapy but could have value in combination with other drugs, especially for patients who have exhausted therapeutic options. In this review, we highlight precision medicine in leukaemia and the role of drug repurposing. Specifically, we discuss the several screening methods via chemoinformatic, in vitro, and ex vivo that have facilitated and accelerated the drug repurposing process.

Muscle mass and strength are subjected to several regulations. We found endocrine signals such as growth hormone, insulin-like growth factor 1, testosterone, thyroid hormones, and glucocorticoids among them. Neural inputs also influence muscle development, modulating mass and strength. Among the external stimuli that modulate these muscular features is physical training such as resistance and endurance training. Specifically, resistance training can mediate an increase in muscle mass by hypertrophy in adults, but the effects in children and adolescents are full of myths for most of the population. However, the evidence shows that the impact of resistance training on children and adolescents is clear and provides a wide range of benefits. However, qualified professionals must be available since exercise prescription and subsequent supervision must follow this population's abilities, needs, and interests.

Chronic wounds including vascular ulcers, diabetic ulcers, pressure ulcers, and burn wounds show delayed progress through the healing process. Some of their common features are prolonged inflammation, persistent infection, and presence of biofilms resistant to antimicrobials and host immune response. Biofilm formation by opportunistic pathogens is a major problem in chronic wound management. Some of the commonly and traditionally used chronic wound management techniques are physical debridement and cleansing. In recent years, novel techniques based on anti-biofilm agents are explored to prevent biofilm-associated infections and facilitate wound healing. In this chapter, the role of biofilms formed by the ESKAPE pathogens (Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa) and Candida species in delayed wound healing have been discussed. The current and emerging techniques in the detection of biofilms for the management of wounds have been focused. The limitations of the existing therapeutics and novel wound management strategies have been deliberated.

Background Extended-spectrum β-lactamases (ESBLs)-producing Klebsiella pneumoniae is reported worldwide increasingly. However, studies on ESBLs are still scarce in Ethiopia. Therefore, the current study aimed to determine the magnitude and resistance patterns of ESBL-producing K. pneumoniae as well as the frequency of ESBL-encoding genes.Methods A cross-sectional study was conducted from September 2018 to February 2019 at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia among a total of 132 non-duplicate K. pneumoniae isolates. Phenotypic detection of ESBL production was done using Combined Disc Test. ESBL-encoding genes of blaCTX-M, blaTEM, and blaSHV were detected through multiplex PCR.Results The magnitude of ESBL production was 102/132 (77.3%). ESBL positive isolates were 100% resistant to ceftriaxone, cefotaxime, and cefuroxime. Co-resistance of ESBL-positive isolates to other non β-lactam antimicrobials was high to trimethoprim-sulfamethoxazole (96.1%) followed by tetracycline (75.5%) and gentamicin (73.5%). However, these isolates showed high susceptibility to amikacin (96.1%) and meropenem (89.2%). From the total ESBL-positive isolates, 82.6%, 73.5%, and 75% carried blaCTX-M, blaTEM, and blaSHV genes, respectively. The majority 78/102 (76.5%) of ESBL-positive isolates harbored all three types of ESBL genes simultaneously.Conclusions The magnitude of ESBL-producing K. pneumoniae isolates was very alarming in the study area. The co-occurrence of blaCTX-M, blaTEM, and blaSHV genes is high, demanding large-scale studies to evaluate the presence of antimicrobial resistance super-clones. ESBL-producing isolates showed high resistance to most of the antimicrobials, needing phenotypic detection of ESBL regularly for better management of patients.