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Medulloblastoma (MB) is a highly malignant brain tumor that occurs primarily in children. Although surgery, radiation and high-dose chemotherapy have led to increased survival, many MB patients still die from their disease, and patients who survive suffer severe long-term side effects as a consequence of treatment. Thus, more effective and less toxic therapies for MB are critically important. Development of such therapies depends in part on identification of genes that are necessary for growth and survival of tumor cells. Survivin is an inhibitor of apoptosis protein that regulates cell cycle progression and resistance to apoptosis, is frequently expressed in human MB and when expressed at high levels predicts poor clinical outcome. Therefore, we hypothesized that Survivin may have a critical role in growth and survival of MB cells and that targeting it may enhance MB therapy. Here we show that Survivin is overexpressed in tumors from patched (Ptch) mutant mice, a model of Sonic hedgehog (SHH)-driven MB. Genetic deletion of survivin in Ptch mutant tumor cells significantly inhibits proliferation and causes cell cycle arrest. Treatment with small-molecule antagonists of Survivin impairs proliferation and survival of both murine and human MB cells. Finally, Survivin antagonists impede growth of MB cells in vivo. These studies highlight the importance of Survivin in SHH-driven MB, and suggest that it may represent a novel therapeutic target in patients with this disease.

This study tested a mentoring model that paired trained teens with younger children in an after-school setting to deliver a curriculum aimed at promoting healthier patterns of dietary intake and physical activity. Using a pretest-posttest design, group comparisons were made. Descriptive, independent, and paired t-test analyses with Bonferroni corrections were conducted in a sample of 72 children. Group differences were noted with the intention to eat healthfully. Mentored children demonstrated greater improvement in knowledge, attitudes, efficacy, perceived support, and body mass index (BMI). Teen mentors can effectively impact children's intention to improve health behaviors, which is foundational to normalizing BMI. [ABSTRACT FROM AUTHOR]

PURPOSE/OBJECTIVES: To describe institutional practices related to dietary restrictions for patients with neutropenia to determine whether restrictions are used and when they are implemented and discontinued. DESIGN: Descriptive survey. SAMPLE: 156 institutions belonging to the Association of Community Cancer Centers. METHODS: Mailed survey. FINDINGS: Of the institutions surveyed, 78% (n = 120) placed patients with neutropenia on restricted diets. Participating institutions responded that patients were placed on restricted diets at a variety of different white blood cell and neutrophil counts, including neutrophils < 1,000 (43%) and < 500 (46%). The majority of institutions (92%) placed patients on restricted diets once neutropenia was documented, while only 9% of institutions restricted diets when cancer treatment was initiated. Of the participating institutions, 83% (n = 96) restricted diets only when patients were neutropenic rather than throughout the duration of the chemotherapy regimen. The most commonly restricted foods were fresh fruits and juices (92%), fresh vegetables (95%), and raw eggs (74%). Few institutions restricted tap water (12%). Wine was restricted at 39% of institutions, and beer was restricted at 40% of institutions. CONCLUSIONS: The role of diet in the development of infection in patients with neutropenia is unclear. This unclear role contributes to the variation in dietary restrictions among institutions. IMPLICATIONS FOR NURSING PRACTICE: Additional research should focus on dietary factors contributing to neutropenic infections and establishing criteria for implementation of specific dietary modifications. Nursing assessment should include nutritional status and risk factors for neutropenia and bacterial translocation. Nursing protocols for neutropenic dietary restrictions should be based on research findings. [ABSTRACT FROM AUTHOR]

1 Sulphate conjugation catalyzed by phenol sulphotransferase (PST) is an important pathway in the metabolism of many drugs including triamterene. Variations in PST activity in an easily obtained tissue such as the platelet might reflect individual differences in the sulphate conjugation in other organs and tissues. Human platelets contain at least two forms of PST, a thermolabile (TL) form for which dopamine is a substrate and a thermostable (TS) form for which low concentrations of p-nitrophenol serve as a substrate. 2 p-OH- triamterene, the major metabolite of triamterene, is conjugated with sulphate in vivo. p-OH-triamterene was a substrate for platelet PST with an apparent Michaelis-Menten value of 26 microM. Thermal stability studies indicated that p-OH-triamterene was a substrate for only the TS form of platelet PST. 3 When platelet homogenates from 29 individual subjects were tested, there was a significant correlation between PST activities measured with 4 microM p-nitrophenol and with p-OH- triamterene (r = 0.985, P less than 0.0001) but not between activities measured with dopamine and with p-OH-triamterene (r = 0.023, P greater than 0.2). These results confirmed that p-OH-triamterene was a substrate for only the TS form of human platelet PST. 4 The same 29 subjects were treated with 1 mg/kg of triamterene orally. 24-h urinary excretions of triamterene, p-OH-triamterene and p-OH-triamterene sulphate averaged 15.3%, 6.3% and 78.4%, respectively, of the total of triamterene plus measured metabolites excreted. The excretion of triamterene plus the two metabolites averaged 43.1 +/- 2.6% (mean +/- s.e. mean) of the ingested dose. There was not a significant correlation between the proportion of p-OH-triamterene excreted as sulphate conjugate and the activities of either the TS or TL forms of platelet PST activity. [ABSTRACT FROM AUTHOR]

As spring phenology advances with climate change, so too must the timing of life cycle events. Breeding at the right time is critical in many species as it maximizes fitness. For long-distance migratory birds, flexibility in the duration of the arrival-breeding interval (pre-breeding period) may allow populations to adjust their timing of breeding. However, whether first egg-lay dates are flexible to local environmental conditions after arrival, and if they are constrained by the time needed to replenish energy lost during migration, remains unclear. We investigated the regional flexibility of the arrival-breeding interval in an avian migrant, the purple martin, Progne subis, across their breeding range. We evaluated whether the duration of the arrival-breeding interval was flexible to temperature and precipitation at breeding sites, and if timing was limited by migration rate and stopover duration. We also tested if longer interval durations were associated with higher fledging success. To address our hypotheses, we used a combination of migration tracking, weather and breeding data collected from four regions across eastern North America (26.1° N to 52.4° N latitude). We found the arrival-breeding interval to be shortest in the north and longest in the south. Across all regions, warmer temperatures encountered at breeding grounds were associated with shorter intervals, and faster migration rates led to longer intervals. The length of the interval was not influenced by precipitation or stopover duration. Finally, longer intervals were not associated with higher fledge success. Currently, the longer arrival-breeding intervals in this study system, on average 28.3 days, may provide both early and late-arriving birds with ample time for recovery so birds can lay eggs according to temperature. Any negative effects of faster migration may have been buffered by longer arrival-breeding intervals, as interval length did not determine fledge success. With ongoing climate change, further research is needed to examine if arrival-breeding intervals become constrained by migration timing, which may limit opportunities for migrants to match the timing of breeding with key resources., (© 2024 The Author(s). Journal of Animal Ecology published by John Wiley & Sons Ltd on behalf of British Ecological Society.)

The potential harms related to interventions for adults with suicide-related risk, particularly hospitalization, have been well documented. Much less work has focused on the potential harms related to interventions with youth struggling with suicidal thoughts and behaviors. Young people are most likely to receive mental health services in schools, which are recognized as meaningful sites for effective suicide prevention work. However, no overviews have conceptualized the potential harms to youth when schools engage in ineffective suicide prevention efforts. In this article, we discuss three prominent overlapping areas of potential harms: (1) privacy-related, (2) relationship-related, and (3) mental health-related. We then discuss key factors thought to influence the development and maintenance of these potential harms. We conclude by noting ways in which school-based mental health providers may attempt to reduce unintentional harms in this area, with an overarching goal of helping support school mental health providers and the youth they serve., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Certain associations observed in the National Birth Defects Prevention Study (NBDPS) contrasted with other research or were from areas with mixed findings, including no decrease in odds of spina bifida with periconceptional folic acid supplementation, moderately increased cleft palate odds with ondansetron use and reduced hypospadias odds with maternal smoking., Objectives: To investigate the plausibility and extent of differential participation to produce effect estimates observed in NBDPS., Methods: We searched the literature for factors related to these exposures and participation and conducted deterministic quantitative bias analyses. We estimated case-control participation and expected exposure prevalence based on internal and external reports, respectively. For the folic acid-spina bifida and ondansetron-cleft palate analyses, we hypothesized the true odds ratio (OR) based on prior studies and quantified the degree of exposure over- (or under-) representation to produce the crude OR (cOR) in NBDPS. For the smoking-hypospadias analysis, we estimated the extent of selection bias needed to nullify the association as well as the maximum potential harmful OR., Results: Under our assumptions (participation, exposure prevalence, true OR), there was overrepresentation of folic acid use and underrepresentation of ondansetron use and smoking among participants. Folic acid-exposed spina bifida cases would need to have been ≥1.2× more likely to participate than exposed controls to yield the observed null cOR. Ondansetron-exposed cleft palate cases would need to have been 1.6× more likely to participate than exposed controls if the true OR is null. Smoking-exposed hypospadias cases would need to have been ≥1.2 times less likely to participate than exposed controls for the association to falsely appear protective (upper bound of selection bias adjusted smoking-hypospadias OR = 2.02)., Conclusions: Differential participation could partly explain certain associations observed in NBDPS, but questions remain about why. Potential impacts of other systematic errors (e.g. exposure misclassification) could be informed by additional research., (© 2023 John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Objectives: To understand how frailty and healthcare delays differentially mediate the association between sexual and gender minority older adults (OSGM) status and healthcare utilization., Materials and Methods: Data from the All of Us Research Program participants ≥50 years old were analyzed using marginal structural modelling to assess if frailty or healthcare delays mediated OSGM status and healthcare utilization. OSGM status, healthcare delays, and frailty were assessed using survey data. Electronic health record (EHR) data was used to measure the number of medical visits or mental health (MH) visit days, following 12 months from the calculated All of Us Frailty Index. Analyses adjusted for age, race and ethnicity, income, HIV, marital status ± general MH (only MH analyses)., Results: Compared to non-OSGM, OSGM adults have higher rates of medical visits (adjusted rate ratio [aRR]: 1.14; 95% CI: 1.03, 1.24) and MH visits (aRR: 1.85; 95% CI: 1.07, 2.91). Frailty mediated the association between OSGM status medical visits (Controlled direct effect [Rcde] aRR: 1.03, 95% CI [0.87, 1.22]), but not MH visits (Rcde aRR: 0.37 [95% CI: 0.06, 1.47]). Delays mediated the association between OSGM status and MH visit days (Rcde aRR: 2.27, 95% CI [1.15, 3.76]), but not medical visits (Rcde aRR: 1.06 [95% CI: 0.97, 1.17])., Discussion: Frailty represents a need for medical care among OSGM adults, highlighting the importance of addressing it to improve health and healthcare utilization disparities. In contrast, healthcare delays are a barrier to MH care, underscoring the necessity of targeted strategies to ensure timely MH care for OSGM adults., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)