This review covers the current aspects of leishmaniasis including marketed drugs, new antileishmanial agents, and possible drug targets of antileishmanial agents.

This study aimed to evaluate the accuracy of the HOSPITAL Score (Haemoglobin level at discharge, Oncology at discharge, Sodium level at discharge, Procedure during hospitalization, Index admission, number of hospital admissions, Length of stay) LACE index (Length of stay, Acute/emergent admission, Charlson comorbidy index score, Emerency department visits in previous 6 months) and LACE+ index in predicting 30-day readmission in patients with diastolic dysfunction. Heart failure remains one of the most common hospital readmissions in adults, leading to significant morbidity and mortality. Different models have been used to predict 30-day hospital readmissions. All adult medical patients discharged from the SIU School of Medicine Hospitalist service from 12 June 2016 to 12 June 2018 with an International Classification of Disease, 10th Revision, Clinical Modification diagnosis of diastolic heart failure were studied retrospectively to evaluate the performance of the HOSPITAL Score, LACE index and LACE+ index readmission risk prediction tools in this patient population. Of the 730 patient discharges with a diagnosis of heart failure with preserved ejection fraction (HFpEF), 692 discharges met the inclusion criteria. Of these discharges, 189 (27%) were readmitted to the same hospital within 30 days. A receiver operating characteristic evaluation showed C-statistic values to be 0.595 (95% CI 0.549 to 0.641) for the HOSPITAL Score, 0.551 (95% CI 0.503 to 0.598) for the LACE index and 0.568 (95% CI 0.522 to 0.615) for the LACE+ index, indicating poor specificity in predicting 30-day readmission. The result of this study demonstrates that the HOSPITAL Score, LACE index and LACE+ index are not effective predictors of 30-day readmission for patients with HFpEF. Further analysis and development of new prediction models are needed to better estimate the 30-day readmission rates in this patient population.

Lipoxygenases (LOXs) are lipid metabolizing enzymes that catalyze the di-oxygenation of polyunsaturated fatty acids to generate active eicosanoid products. 12-lipoxygenases (12-LOXs) primarily oxygenate the 12th carbon of its substrates. Many studies have demonstrated that 12-LOXs and their eicosanoid metabolite 12-hydroxyeicosatetraenoate (12-HETE), have significant pathological implications in inflammatory diseases. Increased level of 12-LOX activity promotes stress (both oxidative and endoplasmic reticulum)-mediated inflammation, leading to damage in these tissues. 12-LOXs are also associated with enhanced cellular migration of immune cells—a characteristic of several metabolic and autoimmune disorders. Genetic depletion or pharmacological inhibition of the enzyme in animal models of various diseases has shown to be protective against disease development and/or progression in animal models in the setting of diabetes, pulmonary, cardiovascular, and metabolic disease, suggesting a translational potential of targeting the enzyme for the treatment of several disorders. In this article, we review the role of 12-LOXs in the pathogenesis of several diseases in which chronic inflammation plays an underlying role.

It is well known that a chronic state of elevated reactive oxygen species (ROS) in pancreatic β-cells impairs their ability to release insulin in response to elevated plasma glucose. Moreover, at its extreme, unmitigated ROS drives regulated cell death. This dysfunctional state of ROS buildup can result both from genetic predisposition and environmental factors such as obesity and overnutrition. Importantly, excessive ROS buildup may underlie metabolic pathologies such as type 2 diabetes mellitus. The ability to monitor ROS dynamics in β-cells in situ and to manipulate it via genetic, pharmacological, and environmental means would accelerate the development of novel therapeutics that could abate this pathology. Currently, there is a lack of models with these attributes that are available to the field. In this study, we use a zebrafish model to demonstrate that ROS can be generated in a β-cell-specific manner using a hybrid chemical genetic approach. Using a transgenic nitroreductase-expressing zebrafish line, Tg(ins:Flag-NTR)s950, treated with the prodrug metronidazole (MTZ), we found that ROS is rapidly and explicitly generated in β-cells. Furthermore, the level of ROS generated was proportional to the dosage of prodrug added to the system. At high doses of MTZ, caspase 3 was rapidly cleaved, β-cells underwent regulated cell death, and macrophages were recruited to the islet to phagocytose the debris. Based on our findings, we propose a model for the mechanism of NTR/MTZ action in transgenic eukaryotic cells and demonstrate the robust utility of this system to model ROS-related disease pathology.

IMPORTANCEThe cardiovascular outcome in selected populations when sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) are emerging as standard therapy is not clearly understood. It is important to learn the magnitude of cardiovascular benefit using SGLT2-Is across the select subgroups that include both sexes and multiple age and racial and ethnic groups. OBJECTIVESTo evaluate the association between use of SGLT2-Is and cardiovascular benefits in a prespecified group in a larger sample size using data obtained from randomized clinical trials. DATA SOURCESSearch of electronic databases PubMed, Google Scholar, Web of Science, and Cochrane from inception to January 10, 2021, with additional studies identified through conference papers and meeting presentations, ClinicalTrials.gov, and reference lists of published studies. STUDY SELECTION Placebo-controlled randomized clinical trials in which participants had atherosclerotic cardiovascular disease (ASCVD) or risk factors for ASCVD, diabetes, or heart failure and which reported the primary outcome were included in this study. Multicenter observational and nonobservational studies and those with different outcomes of interest were excluded. DATA EXTRACTION AND SYNTHESIS Medical Subject Heading search terms included SGLT2-I and multiple cardiovascular outcomes in different combinations. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. The analysis of all outcomes was performed using a Mantel-Haenszel equation and the randomeffects model. MAIN OUTCOMES AND MEASURES Six efficacy outcomes of SGLT2-I use (cardiovascular deathand hospitalization for heart failure [HHF] as the primary outcome and major adverse cardiovascular event, HHF, cardiovascular death, acute myocardial infarction, and all-cause mortality as secondary outcomes), were evaluated. Subgroup analysis was performed for the primary outcome of cardiovascular death or HHF. Odds ratios (ORs) and 95% CIs were used to compare 2 interventions. RESULTSTen studies with 71 553 participants were included, among whom 39 053 received SGLT2-Is; among studies that reported these data, 28 809 were men and 15 655 were women (mean age, 65.2 [range, 61.9-70.0] years). Race and ethnicity were defined in the original trials and were categorized as Asian, Black, or other (6900 participants) and White (26 646 participants) for the purposes of this analysis (the category "other" was not specified consistently). In terms of age, 16 793 were younger than 65 years and 17 087 were 65 years or older. At a mean follow-up 2.3 (range, (continued) Key Points Question What is the updated magnitude of benefit associated with sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) on outcome of cardiovascular death or hospitalization for heart failure (HHF) in different select subgroups of patients? Findings This meta-analysis of 10 highquality randomized clinical trials (71 553 participants) found that use of SGLT2-Is was associated with lower occurrence of cardiovascular death...