Studies suggest that biological sex influences susceptibility to kidney diseases with males demonstrating greater risk for developing ischemic acute kidney injury (AKI). Sex-related differences in mitochondrial function and homeostasis exist, likely contributing to sexual dimorphism in kidney injury, but the mechanisms are not well characterized. Our observations reveal lower baseline expression of Sirtuin-3 (Sirt3, a major mitochondrial acetyltransferase) in the kidneys of male mice versus females. We tested the hypothesis that differential expression of kidney Sirt3 may mediate sexual dimorphism in AKI using a bilateral kidney ischemia-reperfusion injury (IRI) model and three transgenic mouse models (1) mice with global transgenic overexpression of Sirt3; (2) mice with inducible, kidney tubule-specific Sirt3 knockdown (iKD); and (3) mice with global Sirt3 knockout. Low mitochondrial Sirt3 (mtSirt3) in males versus females is associated with development of kidney tubular epithelium vacuoles, increased mitochondrial ROS and susceptibility to IRI. Transgenic overexpression of Sirt3 in males protects against kidney IRI and development of tubular epithelium vacuoles. In both sexes, mice with partial kidney tubular epithelium-specific Sirt3 knockdown display intermediate - while global Sirt3 knockout mice display the highest susceptibility to IRI. Female Sirt3 iKD mice demonstrate decreased survival and kidney function after IRI indistinguishable from control males, abolishing the protective effects observed in females. Mechanistically, observed differences in kidney mtSirt3 are sex hormone-dependent; estradiol increases - while testosterone decreases mtSirt3 protein. Our results demonstrate that Sirt3 is an important contributor to the observed sex-related differences in IRI susceptibility, and a potential therapeutic target in the clinical management of AKI. Antimicrobial resistance is a major health concern worldwide. Community pharmacists can play an important role in rational antibiotic use. This study aimed to evaluate the perception and practices of community pharmacists regarding antimicrobial stewardship (AMS) in Lahore, Pakistan. A descriptive cross-sectional study was conducted among community pharmacists in Lahore from 1 November 2017 to 31 December 2017. A self-administered questionnaire was used for data collection. Non-probability convenience sampling was performed to select community pharmacists. Descriptive statistics were applied and Mann-Whitney U-tests and Kruskal-Wallis tests were performed to compare independent groups using SPSS v.20.0. A P-value of <0.05 was considered statistically significant. Perception and practice scores were determined to access community pharmacist knowledge regarding AMS. A score of 0.5-1 was considered to be very good. The overall response rate was 70.9%. Sex, age, work experience and education level did no, there should be strict implementation of guidelines for dispensing antibiotics in order to rationalise antibiotic use and decrease antimicrobial resistance. The Klebsiella pneumoniae carbapenemase (KPC) is disseminated worldwide mostly by plasmids. However, in Pseudomonas aeruginosa chromosomal mutations are more frequently responsible for resistance to carbapenems than the acquisition of mobile elements harbouring carbapenemases genes. Indeed, although uncommon, KPC-2-producing P. aeruginosa has appeared more frequently, including in Brazil. Oditrasertib purchase Here we report the first genomic analysis of a plasmid-mediated KPC-2 in an extensively drug-resistant (XDR) P. aeruginosa isolated in Santa Catarina, Brazil. Antimicrobial susceptibility testing was performed according to CLSI 2020 guidelines. The genome was sequenced using an Illumina MiSeq platform and the data were analysed using SPAdes and Prokka. In silico predictions were fulfilled using curated bioinformatics tools. Pseudomonas aeruginosa strain MIMA_PA2.1 (JACGTM000000000) was classified as XDR, belongs to sequence type 312 (ST312) and harbours the bla gene located on a small (7975 bp) IncU plasmid. This plamediated blaKPC in P. aeruginosa in Latin America. New antituberculosis agents active against drug-resistant and non-replicating tubercle bacilli are required. We evaluated a previously identified hit, 2-(((2-hydroxyphenyl)amino)methylene)-5,5-dimethylcyclohexane-1,3-dione (PAMCHD), against several clinical Mycobacterium tuberculosis isolates, including multidrug-resistant (MDR) strains and non-replicating drug-tolerant persisters of M. tuberculosis H37Rv. PAMCHD's potential against drug-resistant M. tuberculosis was investigated by broth microdilution. CFU enumeration was performed to determine PAMCHD's activity against five types of dormant bacilli. No significant differences in MICs of PAMCHD were observed against M. tuberculosis H37Rv (2.5-5 µg/mL) and eight drug-susceptible strains (1.25-5 µg/mL) as well as drug-resistant strains including six isoniazid (INH)-resistant (2.5-10 µg/mL), one INH+ethambutol (EMB)-resistant (5 µg/mL), one rifampicin (RIF)+EMB-resistant (5 µg/mL) and three MDR (2.5-10 µg/mL) strains. Thus, PAMCHD maintains activity againe findings warrant further studies of PAMCHD for further anti-TB drug development. The development of leptomeningeal disease (LMD) among melanoma patients is associated with short survival. Unspecific clinical symptoms and imprecise diagnostic criteria often delay diagnosis. Because melanoma patients with LMD have been excluded from most clinical trials, the efficacy of immune checkpoint blockade (ICB) and targeted therapies (TTs) has not been adequately investigated among these patients. We performed a retrospective study in two tertiary-referral skin cancer centres to evaluate the clinical characteristics, diagnostics, treatments, and overall survival (OS) of melanoma patients with LMD between June 2011 and March 2019. In total, 52 patients were included. The median age at LMD diagnosis was 58 years. Most patients (n=30, 58%) were men. The median time from the first diagnosis of unresectable disease to the first diagnosis of LMD was 8.5 months (range 0-91.5 months). Most patients (65%, n=34) were BRAF V600 mutated. Sixteen patients (31%) presented with LMD only, whereas 36 patients (69%) presented with concomitant brain metastases at LMD diagnosis.