Through the synthesis of a focused library and SAR investigations, a more potent analogue of gemmacin (discovered in a previous diversity-oriented synthesis (DOS) campaign), gemmacin B, was discovered.

The authors conducted a cross-sectional survey of Massachusetts school nurses examining return-to-learn practices for children recovering from concussion in prekindergarten through high school. Regardless of school setting, all students received academic accommodations to support learning during recovery. School nurses perceived less benefit to prolonged cognitive rest (>4 days) for high school students relative to students in elementary school, but provided academic accommodations to them for comparatively longer periods of time (10-14 days vs 6-10 days). In all settings, respondents indicated a need for improved communication among treating physicians, parents, and school personnel, as well as improved education and standardized management tools for younger children and those who sustain non-sport-related injuries. Despite serving children at different developmental stages, school return-to-learn practices are essentially the same in primary and secondary schools, highlighting the need for standardized, developmentally appropriate return-to-learn plans and additional education for the providers and school personnel who implement them.

Background & Aims: RET receptor tyrosine kinase is necessary for enteric nervous system (ENS) development. Loss-of-function RET mutations cause Hirschsprung disease (HSCR), in which infants are born with aganglionic bowel. Despite surgical correction, HSCR patients often experience chronic defecatory dysfunction and enterocolitis, suggesting that RET is important after development. To test this hypothesis, we determined the location of postnatal RET and its significance in gastrointestinal (GI) motility. Methods: RetCFP/+ mice and human transcriptional profiling data were studied to identify the enteric neuronal and epithelial cells that express RET. To determine whether RET signaling in these cells regulates adult gut motility in vivo, genetic and pharmacologic approaches were used to disrupt RET in either all RET-expressing cells, a major subset of enteric neurons, or intestinal epithelial cells. Results: Distinct subsets of enteric neurons and enteroendocrine cells expressed RET in the adult intestine. RET disruption in the intestinal epithelium, rather than in enteric neurons, slowed GI motility selectively in adult male mice. This effect was phenocopied by RET kinase inhibition. Most RET+ epithelial cells were either enterochromaffin cells that release serotonin (5-HT) or L-cells that release peptide YY (PYY), both of which can alter motility. RET kinase inhibition exaggerated PYY release in a nutrient-dependent manner without altering 5-HT secretion. PYY receptor blockade fully rescued dysmotility in mice lacking epithelial RET. Conclusion: RET signaling normally limits nutrient-dependent PYY release from L-cells and this activity is necessary for normal intestinal motility in male mice. These effects could contribute to post-operative dysmotility in HSCR, which predominantly affects males, and uncovers a mechanism that could be targeted to treat post-prandial GI dysfunction.

Functional gastrointestinal disorders (FGIDs) have prominent sex differences in incidence, symptoms, and treatment response that are not well understood. Androgens are steroid hormones present at much higher levels in males than females and could be involved in these differences. In adults with irritable bowel syndrome (IBS), a FGID that affects 5-10% of the population worldwide, we found that free testosterone levels were lower than those in healthy controls and inversely correlated with symptom severity. To determine how this diminished androgen signaling could contribute to bowel dysfunction, we depleted gonadal androgens in adult mice and found that this caused a profound deficit in gastrointestinal transit. Restoring a single androgen hormone was sufficient to rescue this deficit, suggesting that circulating androgens are essential for normal bowel motility in vivo. To determine the site of action, we probed androgen receptor expression in the intestine and discovered, unexpectedly, that a large subset of enteric neurons became androgen-responsive upon puberty. Androgen signaling to these neurons was required for normal colonic motility in adult mice. Taken together, these observations establish a role for gonadal androgens in the neural regulation of bowel function and link altered androgen levels with a common digestive disorder.

This practice analysis acknowledges the changing nature of healthcare, recognizing the need for a 7-day therapy service on an Emergency Assessment Unit within the acute sector. A critical reflection on practice is offered to share the experiences of trialling a 7-day therapy service as a solution to managing today's political, economic, and demographic challenges. A 12-month pilot of 4-hour therapy shifts at the weekend demonstrated therapists could discharge 40% of patients assessed on the Emergency Assessment Unit; thus evidencing the need for a permanently funded 7-day service to sustain these results long term. Improved access to therapy on a Saturday and Sunday enhances equality of service provision, patient outcomes and weekend discharge rates. The findings are relevant to all occupational therapists and physiotherapists working in the acute sector.

ObjectiveThe purpose of our study was to characterise return-to-learn practices following concussion in primary and secondary schools, particularly with regard to prescribed cognitive rest.DesignCross-sectional survey.SettingMassachusetts.ParticipantsNine hundred member of the Massachusetts School Nurse Research Network (MASNRN) employed full or part-time at a public, private, or charter school serving pre-school through the 12th grade.Outcome measuresPrescribed rest (actual) versus perceived benefit of rest.Main resultsA majority of respondents expressed the opinion that more prolonged cognitive rest benefits recovery, with 53.6% endorsing 4–10 days as beneficial compared to 44.3% endorsing 3 days or less. Only 2.1% felt no benefit to cognitive rest following concussion. The average number of medically advised rest (actual) was equal for older and younger students (4.5 days). School nurses perceived less benefit to prolonged cognitive rest (>4 days) for high school students relative to students in elementary school [2 (4, n=97)=11.05, p<0.05], but provided academic accommodations to high school students for comparatively longer periods of time (10–14 days vs. 6–10 days) [F(2,89)=4.74, p=0.011].ConclusionsCounter to the practice of administering accommodations for fewer days in younger students, school nurses perceived greater benefit to shorter periods of cognitive rest (3 days or less) for older children (high school age) relative to elementary school and middle school children. In all settings, schools rest is overprescribed in light of recent finding indicating that prolonged rest (beyond two to three days) may delay recovery.Competing interestsNone.

No abstract

No abstract