Design, synthesis and structure-activity relationships of substituted oxazole-benzamide antibacterial inhibitors of FtsZ.

The design, synthesis and structure-activity relationships of a series of oxazole-benzamide inhibitors of the essential bacterial cell division protein FtsZ are described. Compounds had potent anti-staphylococcal activity and inhibited the cytokinesis of the clinically-significant bacterial pathogen Staphylococcus aureus. Selected analogues possessing a 5-halo oxazole also inhibited a strain of S. aureus harbouring the glycine-to-alanine amino acid substitution at residue 196 of FtsZ which conferred resistance to previously reported inhibitors in the series. Substitutions to the pseudo-benzylic carbon of the scaffold improved the pharmacokinetic properties by increasing metabolic stability and provided a mechanism for creating pro-drugs. Combining multiple substitutions based on the findings reported in this study has provided small-molecule inhibitors of FtsZ with enhanced in vitro and in vivo antibacterial efficacy.

Eating Disorders: Assessing Its Prevalence and Pattern Among Adults With Type 2 Diabetes.

BACKGROUND: Eating disorders (EDs) are severe and multifaceted mental health issues that affect a person's perception of their body weight in relationship with food. Existing evidence shows that EDs significantly affect the physical and emotional health of individuals with Type-2 Diabetes (T2D) and are associated with impaired metabolic control and a high risk of medical complications, including higher mortality rates. However, there is a paucity of research looking into the prevalence of EDs. OBJECTIVE: A cross-sectional study was conducted to map the prevalence of EDs and to assess its pattern among adults with T2D from Ahmedabad City, Gujarat, India. METHODOLOGY: Two hundred fifty-four T2D individuals aged 30-60 were enrolled in the study. A questionnaire was developed using the Sick, Control, One, Fat, Food (SCOFF) questionnaire and a five-question screening tool intended to identify the possibility of EDs as well as the Eating Disorder Examination-Questionnaire (EDEQ), which is used to identify the pattern of EDs with subscales like Restraint, Eating Concern, Shape Concern, and Weight Concern. Written informed consent was obtained from all participants. Descriptive statistics, Pearson's Correlation, and Logistic Regression analysis were used. A p-value of < 0.05 was considered significant. RESULTS:  The results revealed that 90 (35%) of the total participants were at a high risk of EDs. Among these, 54 (21% of the total population) were males, and 36 (14% of total participants) were females. There was a mild statistically significant negative correlation between age and exercise with the presence of ED (r = -0.151, p = 0.016 and r = -0.186, p = 0.003, respectively), while education showed a significant positive correlation (r = 0.150, p = 0.017). Males had significantly higher scores for eating concerns than females (19.75±4.88 vs 17.88±5.92; p = 0.008). The logistic regression model revealed that education was a significant predictor of EDs (OD = 1.47, 95% CI 1.00-2.16 and p = 0.04). CONCLUSION: The study identified that people with T2D are at risk of EDs, and eating concerns worry them the most. Thus, counseling sessions should focus on identifying the determinants of EDs and educating the patients regarding quality eating. This will have implications in addressing the other morbidities as well as health risks related to BMI; especially obesity as it is more prevalent in the T2D population.

Exploring the Impact of Optimized Probiotic Supplementation Techniques on Diabetic Nephropathy: Mechanisms and Therapeutic Potential.

Worldwide, diabetic nephropathy (DN) is a significant contributor to end-stage renal failure and chronic kidney disease. Probiotic supplementation has recently gained popularity as a potential nutritional therapy in several clinical trials aimed at improving renal function, inflammation, oxidative stress, dyslipidemia, glycemic control, and inflammation. However, they still need to undergo a thorough assessment of DN. It is crucial that the optimal dosage, duration, and combination of probiotic strains administered for the purpose of slowing down the advancement of DN be assessed. Based on the available publications, including relevant randomized controlled trials, systematic reviews, and meta-analysis from 2013-2023 from search engines like MEDLINE (PubMed), Scopus, and Web of Science, a literature review was generated using the keywords "gut microbiota," "gut microbiome," "diabetic kidney disease," "diabetic nephropathy," "probiotic," and "prebiotic." Multiple clinical trials focusing on probiotic administration techniques revealed changes in renal, glucose, and lipid biomarkers. Probiotic supplementation using Bifidobacterium bifidum, Lactobacillus acidophilus, and Streptococcus thermophilus for 12 weeks indicated a reduction in glycosylated hemoglobin, fasting blood glucose, and the microalbuminuria/creatinine ratio. Multispecies as well as single-species probiotic administration containing Lactobacillus, Bifidobacterium, and Streptococcus thermophilus spp. greater than 4*109 colony forming units (CFU)/day for 8-12 weeks in DN patients improves renal metabolic markers and reduces the progression of disease patterns. Optimal supplementation techniques of probiotics in conjunction with prebiotics and synbiotics in DN benefit glycaemic control, renal function, blood lipid profile, inflammation, and oxidative stress. Future randomized controlled trials supplementing specific probiotics coupled with prebiotics and synbiotics, with larger sample sizes and longer follow-up times, will generate more reliable findings for the impact of probiotic supplementation on DN.