ABSTRACT
Analogs containing a central 3-pyrrolin-2-one core with different methoxyphenyl and/or indole substituents were prepared and tested for anti-proliferative activity in U-937 cells. The most efficacious analogs were non-rigid, (non-fused) contained methoxyaryl groups located at the 4-position, and contained either methoxyaryl or indole groups located at the 3-position. Both the number of methoxy groups contained in the substituents and the particular location of the indole rings with respect to the lactam carbonyl had significant affects on anti-proliferative activity. This work provides a framework to better understand structure-activity relationships for inducing anti-proliferative activity in diaryl heterocyclic scaffolds.
Subject(s)
Antineoplastic Agents/pharmacology , Pyrrolidinones/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cyclization , Heterocyclic Compounds, 4 or More Rings/chemical synthesis , Heterocyclic Compounds, 4 or More Rings/chemistry , Heterocyclic Compounds, 4 or More Rings/pharmacology , Humans , Pyrrolidinones/chemical synthesis , Pyrrolidinones/chemistry , Structure-Activity RelationshipABSTRACT
Eating disorders, especially anorexia nervosa, are complex and devastating illnesses. Although eating disorders have a high mortality rate and are relatively common, there are many barriers for those seeking treatment. Provider training and education, weight bias among health care providers, geographical and language barriers, and a lack of options because of insurance restrictions prevent many families from receiving appropriate care, especially in smaller or rural communities. In those areas, providers are left to piece together treatment using a small number of other providers from different disciplines who have a willingness to work with this population. Outpatient family based treatment is an evidenced-based treatment of anorexia nervosa and relies on a multidisciplinary approach to care. Community-based care teams can be an effective way to treat those with eating disorders seeking family based treatment. There are several strategies for building collaborative teams that can provide comprehensive and accessible care to those with few options. [Pediatr Ann. 2024;53(1):e22-e27.].
Subject(s)
Feeding and Eating Disorders , Humans , Feeding and Eating Disorders/therapy , Ambulatory Care , Health Personnel , Rural Population , Patient Care TeamABSTRACT
Probiotics are commonly prescribed to promote a healthy gut microbiome in children. Our objective was to investigate the effects of probiotic supplementation on growth outcomes in children 0-59 months of age. We conducted a systematic review and meta-analysis which included randomized controlled trials (RCTs) that administered probiotics to children aged 0-59 months, with growth outcomes as a result. We completed a random-effects meta-analysis and calculated a pooled standardized mean difference (SMD) or relative risk (RR) and reported with a 95% confidence interval (CI). We included 79 RCTs, 54 from high-income countries (HIC), and 25 from low- and middle-income countries (LMIC). LMIC data showed that probiotics may have a small effect on weight (SMD: 0.26, 95% CI: 0.11-0.42, grade-certainty = low) and height (SMD 0.16, 95% CI: 0.06-0.25, grade-certainty = moderate). HIC data did not show any clinically meaningful effect on weight (SMD: 0.01, 95% CI: -0.04-0.05, grade-certainty = moderate), or height (SMD: -0.01, 95% CI: -0.06-0.04, grade-certainty = moderate). There was no evidence that probiotics affected the risk of adverse events. We conclude that in otherwise healthy children aged 0-59 months, probiotics may have a small but heterogenous effect on weight and height in LMIC but not in children from HIC.