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Population genetics seeks to illuminate the forces shaping genetic variation, often based on a single snapshot of genomic variation. However, utilizing multiple sampling times to study changes in allele frequencies can help clarify the relative roles of neutral and non-neutral forces on short time scales. This study compares whole-genome sequence variation of recently collected natural population samples of Drosophila melanogaster against a collection made approximately 35 years prior from the same locality-encompassing roughly 500 generations of evolution. The allele frequency changes between these time points would suggest a relatively small local effective population size on the order of 10,000, significantly smaller than the global effective population size of the species. Some loci display stronger allele frequency changes than would be expected anywhere in the genome under neutrality-most notably the tandem paralogs Cyp6a17 and Cyp6a23, which are impacted by structural variation associated with resistance to pyrethroid insecticides. We find a genome-wide excess of outliers for high genetic differentiation between old and new samples, but a larger number of adaptation targets may have affected SNP-level differentiation versus window differentiation. We also find evidence for strengthening latitudinal allele frequency clines northern-associated alleles have increased in frequency by an average of nearly 2.5% at SNPs previously identified as clinal outliers, but no such pattern is observed at random SNPs. This project underscores the scientific potential of using multiple sampling time points to investigate how evolution operates in natural populations, by quantifying how genetic variation has changed over ecologically relevant timescales.Online behavioral obesity treatment is a promising first-line approach to weight management in primary care. However, little is known about contextual influences on implementation. Understand qualitative contextual factors that affect the implementation process, as experienced by key primary care stakeholders implementing the program. Online behavioral obesity treatment was implemented across a 60-clinic primary care practice network. Patients were enrolled by nurse care managers (NCMs; N = 14), each serving 2-5 practices. NCMs were randomized to one of two implementation conditions-"Basic" (standard implementation) or "Enhanced" (i.e., with added patient tracking features and more implementation strategies employed). NCMs completed qualitative interviews guided by the Consolidated Framework for Implementation Research (CFIR). Interviews were transcribed and analyzed via directed content analysis. Emergent categories were summarized by implementation condition and assigned a valence according to positive/negative influence. Individuals in the Enhanced condition viewed two aspects of the intervention as more positively influencing than Basic NCMs Design Quality & Packaging (i.e., online program aesthetics), and Cost (i.e., no-cost program, clinician time savings). In both conditions, strongly facilitating factors included Compatibility between intervention and clinical context; Intervention Source (from a trusted local university); and Evidence Strength & Quality supporting effectiveness. Findings highlight the importance of considering stakeholders' perspectives on the most valued types of evidence when introducing a new intervention, ensuring the program aligns with organizational priorities, and considering how training resources and feedback on patient progress can improve implementation success for online behavioral obesity treatment in primary care.Understanding the molecular mechanisms underlying pituitary organogenesis and function is essential for improving therapeutics and molecular diagnoses for hypopituitarism. We previously found that deletion of the forkhead factor, Foxo1, in the pituitary gland early in development delays somatotrope differentiation. While these mice grow normally, they have reduced growth hormone expression and free serum insulin-like growth factor-1 (IGF1) levels, suggesting a defect in somatotrope function. FOXO factors show functional redundancy in other tissues, so we deleted both Foxo1 and its closely related family member, Foxo3, from the primordial pituitary. We find that this results in a significant reduction in growth. buy AZD9291 Consistent with this, male and female mice in which both genes have been deleted in the pituitary gland (dKO) exhibit reduced pituitary growth hormone expression and serum IGF1 levels. Expression of the somatotrope differentiation factor, Neurod4, is reduced in these mice. This suggests a mechanism underlying proper somatotrope function is the regulation of Neurod4 expression by FOXO factors. Additionally, dKO mice have reduced Lhb expression and females also have reduced Fshb and Prl expression. These studies reveal FOXO transcription factors as important regulators of pituitary gland function.
Dyslipidemia is a feature of polycystic ovary syndrome (PCOS) and may augment metabolic dysfunction in this population.
Using comprehensive lipidomic profiling and gold-standard metabolic measures, we examined whether distinct lipid biomarkers were associated with metabolic risk in women with and without PCOS.
Using preexisting data and biobanked samples from 76 women (n = 42 with PCOS), we profiled > 700 lipid species by mass spectrometry. Lipids were compared between women with and without PCOS and correlated with direct measures of adiposity (dual x-ray absorptiometry and computed tomography) and insulin sensitivity (hyperinsulinemic-euglycemic clamp), as well as fasting insulin, HbA1c, and hormonal parameters (luteinizing and follicle-stimulating hormones; total and free testosterone; sex hormone-binding globulin [SHBG]; and free androgen index [FAI]). Multivariable linear regression was used with correction for multiple testing.
Despite finding no differences by PCOS status, lysophosphatidylinthese findings in larger cohorts of women with varying PCOS phenotypes.
Social support is a vital psychological health resource for well-being in later life. However, research on the associations of social support has largely excluded sexual minorities. This study compares the association between sources of social support and depressive symptoms across groups of older heterosexual and sexual minority men and women. Sexual minority status herein is based on self-reported sexual histories of having same-sex and opposite-sex only experiences (SSE and OSO).
Based on a pooled cross-sectional data set drawn from 3 waves of the National Social Life, Health, and Aging Project, we used ordinary least squares regression and moderation tests to evaluate how 3 sources of social support-partner, family, friend-are related to depressive symptoms for SSE and OSO men and women.
Results show OSO men and women both had significant negative associations between depressive symptoms and social support regardless of the source. SSE women, in contrast, only have a significant association between high levels of friend support, and SSE men only show significant effects in relation to high levels of partner support.
These results suggest the effects of social support on psychological health are significantly constrained/circumscribed for sexual minority men and women. Interventions designed to decrease symptoms of depression in older sexual minorities through social support are discussed.
These results suggest the effects of social support on psychological health are significantly constrained/circumscribed for sexual minority men and women. Interventions designed to decrease symptoms of depression in older sexual minorities through social support are discussed.A safe and effective vaccine against multidrug-resistant gonorrhea is urgently needed. An experimental peptide vaccine called TMCP2 that mimics an oligosaccharide epitope in gonococcal lipooligosaccharide, when adjuvanted with glucopyranosyl lipid adjuvant-stable emulsion, elicits bactericidal immunoglobulin G and hastens clearance of gonococci in the mouse vaginal colonization model. In this study, we show that efficacy of TMCP2 requires an intact terminal complement pathway, evidenced by loss of activity in C9-/- mice or when C7 function was blocked. In conclusion, TMCP2 vaccine efficacy in the mouse vagina requires membrane attack complex. Serum bactericidal activity may serve as a correlate of protection for TMCP2.Athletes are defined by their ability to move and are often accustomed to pain as it relates to their sports and exercise regime. The forced movement restriction and pain associated with an acute or overuse injury has a profound effect not only on their physical abilities but also on their psychological well-being and social context. With the goal of returning to sport, the rehabilitation focus historically has been on recovery of physical attributes, but more recent research is addressing the psychological factors. This Perspective proposes that-according to the current evidence in sports medicine-the fear that affects choice of treatment, rehabilitation, and return to sports is intertwined with physical capacity and recovery of function. Past injury is also 1 of the main risk factors for a sports injury; therefore, fear of reinjury is not irrational. For an athlete, the fear related to a sports injury encompasses the fear of reinjury along with fear of not being able to return to the sport at their highest performance level-and the fear of having lifelong debilitating pain and symptoms. This Perspective reviews the evidence for the influence of fear of movement and reinjury on choice of treatment, rehabilitation, and return to sport and provides suggestions on how to address this fear during the continuum of treatment and return to sports.
Engaging residents, their proxies, and skilled nursing facility (SNF) staff through effective communication has potential for improving fall-related injury prevention. The purpose of this study was to understand how multiple stakeholders develop and communicate fall-related injury prevention plans to enhance sustained implementation.
Descriptive qualitative study using framework analysis applied to open-ended semistructured interviews (n = 28) regarding experiences of communication regarding fall-related injury prevention, guided by the Patient and Family Engaged Care framework. Participants included residents at high risk of injury and their proxies, nursing assistants, nurses, and a nurse practitioner from 3 SNFs in the Eastern United States (Massachusetts and North Carolina).
Interdisciplinary teams were viewed as essential for injury prevention. However, the roles of the interdisciplinary team members were sometimes unclear. Communication structures were often hierarchical, which reduced engagement resources to improve communication can address barriers related to staff practices, resident characteristics, and time constraints.
Driving cessation is a complex challenge with significant emotional and health implications for people with dementia, which also affects their family care partners. Automated vehicles (AVs) could potentially be used to delay driving cessation and its adverse consequences for people with dementia and their care partners. Yet, no study to date has investigated whether care partners consider AVs to be potentially useful for people with dementia.
This mixed-methods study assessed the views of 20 former or current family care partners of people with dementia on AV use by people with dementia. Specifically, questionnaires and semistructured interviews were used to examine care partners' acceptance of AV use by people with dementia and their views about the potential usefulness of AVs for people with dementia.
The results demonstrated that care partners identified possible benefits of AV use by people with dementia such as their anticipated higher social participation. However, care partners also voiced major concerns around AV use by people with dementia and reported significantly lower levels of trust in and perceived safety of AVs if used by the person with dementia in their care compared to themselves.
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