Cytoneme signaling provides essential contributions to mammalian tissue patterning.

During development, morphogens pattern tissues by instructing cell fate across long distances. Directly visualizing morphogen transport in situ has been inaccessible, so the molecular mechanisms ensuring successful morphogen delivery remain unclear. To tackle this longstanding problem, we developed a mouse model for compromised sonic hedgehog (SHH) morphogen delivery and discovered that endocytic recycling promotes SHH loading into signaling filopodia called cytonemes. We optimized methods to preserve in vivo cytonemes for advanced microscopy and show endogenous SHH localized to cytonemes in developing mouse neural tubes. Depletion of SHH from neural tube cytonemes alters neuronal cell fates and compromises neurodevelopment. Mutation of the filopodial motor myosin 10 (MYO10) reduces cytoneme length and density, which corrupts neuronal signaling activity of both SHH and WNT. Combined, these results demonstrate that cytoneme-based signal transport provides essential contributions to morphogen dispersion during mammalian tissue development and suggest MYO10 is a key regulator of cytoneme function.

Metabolic control of TFH cells and humoral immunity by phosphatidylethanolamine.

T follicular helper (TFH) cells are crucial for B cell-mediated humoral immunity1. Although transcription factors such as BCL6 drive the differentiation of TFH cells2,3, it is unclear whether and how post-transcriptional and metabolic programs enforce TFH cell programming. Here we show that the cytidine diphosphate (CDP)-ethanolamine pathway co-ordinates the expression and localization of CXCR5 with the responses of TFH cells and humoral immunity. Using in vivo CRISPR-Cas9 screening and functional validation in mice, we identify ETNK1, PCYT2, and SELENOI-enzymes in the CDP-ethanolamine pathway for de novo synthesis of phosphatidylethanolamine (PE)-as selective post-transcriptional regulators of TFH cell differentiation that act by promoting the surface expression and functional effects of CXCR5. TFH cells exhibit unique lipid metabolic programs and PE is distributed to the outer layer of the plasma membrane, where it colocalizes with CXCR5. De novo synthesis of PE through the CDP-ethanolamine pathway co-ordinates these events to prevent the internalization and degradation of CXCR5. Genetic deletion of Pcyt2, but not of Pcyt1a (which mediates the CDP-choline pathway), in activated T cells impairs the differentiation of TFH cells, and this is associated with reduced humoral immune responses. Surface levels of PE and CXCR5 expression on B cells also depend on Pcyt2. Our results reveal that phospholipid metabolism orchestrates post-transcriptional mechanisms for TFH cell differentiation and humoral immunity, highlighting the metabolic control of context-dependent immune signalling and effector programs.

Transcriptional Dysregulation Underlies Both Monogenic Arrhythmia Syndrome and Common Modifiers of Cardiac Repolarization.

BACKGROUND: Brugada syndrome (BrS) is an inherited arrhythmia syndrome caused by loss-of-function variants in the cardiac sodium channel gene SCN5A (sodium voltage-gated channel alpha subunit 5) in ≈20% of subjects. We identified a family with 4 individuals diagnosed with BrS harboring the rare G145R missense variant in the cardiac transcription factor TBX5 (T-box transcription factor 5) and no SCN5A variant. METHODS: We generated induced pluripotent stem cells (iPSCs) from 2 members of a family carrying TBX5-G145R and diagnosed with Brugada syndrome. After differentiation to iPSC-derived cardiomyocytes (iPSC-CMs), electrophysiologic characteristics were assessed by voltage- and current-clamp experiments (n=9 to 21 cells per group) and transcriptional differences by RNA sequencing (n=3 samples per group), and compared with iPSC-CMs in which G145R was corrected by CRISPR/Cas9 approaches. The role of platelet-derived growth factor (PDGF)/phosphoinositide 3-kinase (PI3K) pathway was elucidated by small molecule perturbation. The rate-corrected QT (QTc) interval association with serum PDGF was tested in the Framingham Heart Study cohort (n=1893 individuals). RESULTS: TBX5-G145R reduced transcriptional activity and caused multiple electrophysiologic abnormalities, including decreased peak and enhanced "late" cardiac sodium current (INa), which were entirely corrected by editing G145R to wild-type. Transcriptional profiling and functional assays in genome-unedited and -edited iPSC-CMs showed direct SCN5A down-regulation caused decreased peak INa, and that reduced PDGF receptor (PDGFRA [platelet-derived growth factor receptor α]) expression and blunted signal transduction to PI3K was implicated in enhanced late INa. Tbx5 regulation of the PDGF axis increased arrhythmia risk due to disruption of PDGF signaling and was conserved in murine model systems. PDGF receptor blockade markedly prolonged normal iPSC-CM action potentials and plasma levels of PDGF in the Framingham Heart Study were inversely correlated with the QTc interval (P<0.001). CONCLUSIONS: These results not only establish decreased SCN5A transcription by the TBX5 variant as a cause of BrS, but also reveal a new general transcriptional mechanism of arrhythmogenesis of enhanced late sodium current caused by reduced PDGF receptor-mediated PI3K signaling.

"What We're Doing Now Is More Than Water Cooler": Perspectives of Primary Care Leaders on Leading Through (and Beyond) COVID-19.

BACKGROUND: COVID-19 presented numerous challenges to primary care, but little formal research has explored the experience of practice leaders and their strategies for managing teams as the crisis unfolded. OBJECTIVE: Describe the experience of leaders in US primary care delivery organizations, and their strategies for leading teams during COVID-19 and beyond. DESIGN: Qualitative study using semi-structured interviews performed between 9/15/2020 and 8/31/2021. PARTICIPANTS: Purposive sample of 17 clinical leaders in a range of US primary care organizations. APPROACH: An iterative grounded review of interview transcripts was performed, followed by immersion/crystallization analysis. KEY RESULTS: Early in the pandemic, practice leaders reported facing rapid change and the need for constant decision-making, amidst an environment of stress, fear, and uncertainty, but this was buffered by a strong sense of purpose. Later, leaders noted the emergence of layered crises, and evolving challenges including fatigue, burnout, and strained relationships within their organizations and with the communities they serve. Leaders described four interrelated strategies for supporting their teams: (1) Being intentionally present, physically and emotionally; (2) Frequent and transparent communication; (3) Deepening and broadening relationships; (4) Increasing adaptive decision-making, alternating between formal hierarchical and flexible participatory processes. These strategies were influenced by individual leaders' perceived autonomy, which was impacted by the leader's specific role, and organizational size, complexity, and funding model. CONCLUSIONS: As the burnout and workforce crises have accelerated, the identified strategies can be useful to leaders to support teams and build organizational resilience in primary care moving forward.

Reviewing the impact of obesity on inflammatory bowel disease and considerations for optimizing management.

PURPOSE OF REVIEW: This review examines the complex relationship between obesity and inflammatory bowel disease (IBD), encompassing their potentially shared pathogenesis, the impact of obesity on the natural history and treatment outcomes of IBD, and the management of obesity in the patient with IBD. RECENT FINDINGS: Obesity represents a state of chronic inflammation that may not only contribute to IBD pathogenesis, but also influence disease progression, complications, and response to treatment. Increased visceral adiposity may carry negative prognostic implications for disease and treatment-specific outcomes. Antiobesity medications, endoscopic bariatric therapies, and even bariatric surgery may be effective and well tolerated in selected patients with IBD. SUMMARY: The intersection of obesity and IBD presents a significant clinical challenge, with obesity influencing the natural history of IBD and potentially affecting treatment efficacy. As obesity prevalence among IBD patients rises, a tailored approach to management is crucial, taking into account the individualized risks and benefits of various treatment strategies, including lifestyle interventions, pharmacotherapy, endoscopic procedures, and bariatric surgery.

Perinatal mental health and pregnancy-associated mortality: opportunities for change.

Perinatal mental health conditions have been associated with adverse pregnancy outcomes, including maternal death. This quality improvement project analyzed pregnancy-associated death among veterans with mental health conditions in order to identify opportunities to improve healthcare and reduce maternal deaths. Pregnancy-associated deaths among veterans using Veterans Health Administration (VHA) maternity care benefits between fiscal year 2011 and 2020 were identified from national VHA databases. Deaths among individuals with active mental health conditions underwent individual chart review using a standardized abstraction template adapted from the Centers for Disease Control and Prevention (CDC). Thirty-two pregnancy-associated deaths were identified among 39,720 paid deliveries with 81% (n = 26) occurring among individuals with an active perinatal mental health condition. In the perinatal mental health cohort, most deaths (n = 16, 62%) occurred in the late postpartum period and 42% (n = 11) were due to suicide, homicide, or overdose. Opportunities to improve care included addressing (1) racial disparities, (2) mental health effects of perinatal loss, (3) late postpartum vulnerability, (4) lack of psychotropic medication continuity, (5) mental health conditions in intimate partners, (6) child custody loss, (7) lack of patient education or stigmatizing patient education, and (8) missed opportunities for addressing reproductive health concerns in mental health contexts. Pregnancy-associated deaths related to active perinatal mental health conditions can be reduced. Mental healthcare clinicians, clinical teams, and healthcare systems have opportunities to improve care for individuals with perinatal mental health conditions.

Supported decision-making interventions in mental healthcare: A systematic review of current evidence and implementation barriers.

BACKGROUND: There is a growing momentum around the world to foster greater opportunities for the involvement of mental health service users in their care and treatment planning. In-principle support for this aim is widespread across mental healthcare professionals. Yet, progress in mental health services towards this objective has lagged in practice. OBJECTIVES: We conducted a systematic review of quantitative, qualitative and mixed-method research on interventions to improve opportunities for the involvement of mental healthcare service users in treatment planning, to understand the current research evidence and the barriers to implementation. METHODS: Seven databases were searched and 5137 articles were screened. Articles were included if they reported on an intervention for adult service users, were published between 2008 and October 2023 and were in English. Evidence in the 140 included articles was synthesised according to the JBI guidance on Mixed Methods Systematic Reviews. RESULTS: Research in this field remains exploratory in nature, with a wide range of interventions investigated to date but little experimental replication. Overarching barriers to shared and supported decision-making in mental health treatment planning were (1) Organisational (resource limitations, culture barriers, risk management priorities and structure); (2) Process (lack of knowledge, time constraints, health-related concerns, problems completing and using plans); and (3) Relationship barriers (fear and distrust for both service users and clinicians). CONCLUSIONS: On the basis of the barriers identified, recommendations are made to enable the implementation of new policies and programs, the designing of new tools and for clinicians seeking to practice shared and supported decision-making in the healthcare they offer. PATIENT OR PUBLIC CONTRIBUTION: This systematic review has been guided at all stages by a researcher with experience of mental health service use, who does not wish to be identified at this point in time. The findings may inform organisations, researchers and practitioners on implementing supported decision-making, for the greater involvement of people with mental ill health in their healthcare.

A rate threshold mechanism regulates MAPK stress signaling and survival.

Cells are exposed to changes in extracellular stimulus concentration that vary as a function of rate. However, how cells integrate information conveyed from stimulation rate along with concentration remains poorly understood. Here, we examined how varying the rate of stress application alters budding yeast mitogen-activated protein kinase (MAPK) signaling and cell behavior at the single-cell level. We show that signaling depends on a rate threshold that operates in conjunction with stimulus concentration to determine the timing of MAPK signaling during rate-varying stimulus treatments. We also discovered that the stimulation rate threshold and stimulation rate-dependent cell survival are sensitive to changes in the expression levels of the Ptp2 phosphatase, but not of another phosphatase that similarly regulates osmostress signaling during switch-like treatments. Our results demonstrate that stimulation rate is a regulated determinant of cell behavior and provide a paradigm to guide the dissection of major stimulation rate dependent mechanisms in other systems.

Effectiveness and Safety of Antiobesity Medications in Patients With Obesity and Inflammatory Bowel Disease.

INTRODUCTION: Limited data exist evaluating antiobesity medications (AOM) in patients with inflammatory bowel disease (IBD). METHODS: We performed a case-control study evaluating the effectiveness and safety of AOM in patients with IBD with obesity, matched to non-IBD controls. RESULTS: After 12 months, the case (n = 36) and control (n = 36) groups achieved similar percent total body weight loss of -6.9 ± 8.3 and -8.1 ± 7.0 (P = 0.30), respectively. Side effect profiles were similar between groups. Seven patients experienced an IBD flare, all managed medically. DISCUSSION: AOM use in patients with IBD demonstrated similar effectiveness and safety when compared with that observed in the non-IBD population.

The Real-World Effectiveness and Safety of Ustekinumab in the Treatment of Crohn's Disease: Results From the SUCCESS Consortium.

INTRODUCTION: We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD). METHODS: This study used a retrospective, multicenter, multinational consortium of UST-treated CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant medications. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions were assessed using time-to-event analysis, and clinical predictors were assessed by using multivariate Cox proportional hazard analyses. Serious infections and adverse events were defined as those requiring hospitalization or treatment discontinuation. RESULTS: A total of 1,113 patients (51.8% female, 90% prior antitumor necrosis factor exposure) were included, with a median follow-up of 386 days. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions at 12 months were 40%, 32%, 39%, and 30%, respectively. Biologic-naive patients achieved significantly higher rates of clinical and endoscopic remissions at 63% and 55%, respectively. On multivariable analyses, prior antitumor necrosis factor (hazard ratio, 0.72; 95% confidence interval, 0.49-0.99) and vedolizumab exposure (hazard ratio, 0.65; 95% confidence interval, 0.48-0.88) were independently associated with lower likelihoods of achieving endoscopic remission. In patients who experienced loss of remission, 77 of 102 (75%) underwent dose optimization, and 44 of 77 (57%) achieved clinical response. An additional 152 of 681 patients (22.3%) were dose-optimized because of primary nonresponse incomplete response to UST, of whom 40.1% (61 of 152) responded. Serious infections occurred in 3.4% of patients while other noninfectious adverse events (lymphoma [n = 1], arthralgia [n = 6], rash [n = 6], headache [n = 3], hepatitis [n = 3], hair loss [n = 3], neuropathy [n = 1], and vasculitis [n = 1]) occurred in 2.4% of patients. DISCUSSION: UST represents a safe and effective treatment option for CD, with 40% of patients from a highly refractory cohort achieving clinical remission by 12 months. The greatest treatment effect of UST was seen in biologic-naive patients, and dose escalation may recapture clinical response.

An Unconditional Cash Transfer Program for Low-Income New Yorkers Affected by COVID-19.

Early in the pandemic, New York City's public hospital system partnered with multiple philanthropic foundations to offer an unconditional cash transfer program for low-income New Yorkers affected by COVID-19. The $1000 cash transfers were designed to help people meet their most immediate health and social needs and were incorporated into healthcare delivery and contact tracing workflows as a response to the public health emergency. To better understand program recipients' experiences, researchers conducted 150 telephone surveys with randomly sampled cash transfer recipients and 20 in-depth qualitative interviews with purposefully sampled survey participants. Survey participants were predominantly Latinx (87%) and women (65%). The most common reported uses of the $1000 were food and rent. Most participants (79%) reported that without the $1000 cash transfer they would have had difficulty paying for basic expenses or making ends meet, with specific positive effects reported related to food, housing, and ability to work. The majority of survey participants reported that receiving the cash assistance somewhat or greatly improved their physical health (83%) and mental health (89%). Qualitative interview results generally supported the survey findings.

Birth Outcomes Associated With E-Cigarette and Non-E-Cigarette Tobacco Product Use During Pregnancy: An Examination of PATH Data Waves 1-5.

OBJECTIVES: To examine associations of prenatal e-cigarette use to pregnancy and birth outcomes. METHODS: Currently pregnant women (n = 1 037) from Waves 1 through 4 of the Population Assessment of Tobacco and Health Study who had pregnancy or live birth outcome data in a subsequent wave (Waves 2-5; 2013 to 2019). Weighted bivariate and multivariable models\ examined associations between past 30-day tobacco use assessed during pregnancy (any past 30-day e-cigarette use, any past 30-day non-e-cigarette tobacco use, or no past 30-day tobacco use) with adverse pregnancy (miscarriage, abortion, ectopic or tubal pregnancy, stillbirth) and birth outcomes (preterm birth, low birth weight, birth defect, placenta previa, placental abruption, pre-eclampsia) reported in the subsequent wave. RESULTS: Approximately 1% of pregnant women reported past 30-day exclusive e-cigarette use and 3.2% used e-cigarettes and one other tobacco product. Compared to no tobacco use, past 30-day e-cigarette use (exclusive or use with another tobacco product) during pregnancy was not associated with increased odds of an adverse pregnancy or birth outcome in bivariate or multivariable models. Past 30-day non-e-cigarette tobacco use was associated with increased odds of an adverse pregnancy outcome in multivariable models, but not an adverse live birth outcome. Compared to past 30-day cigarette use, past 30-day e-cigarette use during pregnancy was not associated with lowered odds of a birth or pregnancy outcome. CONCLUSIONS: E-cigarette use during pregnancy is rare. Understanding the positive and negative impacts of pre-natal e-cigarette use on women's health may guide public health messaging campaigns. IMPLICATIONS: Results showed that past 30-day e-cigarette use during pregnancy was low, with cigarette smoking remaining the most prevalent form of tobacco use during pregnancy. Current e-cigarette use during pregnancy used either exclusively or with another tobacco product, was not associated with increased risk of an adverse pregnancy, or birth outcome. A small sample size of e-cigarette users and limited information on quantity and frequency of e-cigarette use before and during pregnancy may limit conclusions. Healthcare providers may use this information when discussing the harms and consequences associated with e-cigarette and tobacco use during pregnancy.

Skeletal maturation in male elite youth athletes from the Middle East.

OBJECTIVES: To examine the timing and intensity of skeletal maturation of the radius-ulna-short (RUS) bones in elite youth Arab athletes. METHODS: We compared SuperImposition by Translation And Rotation (SITAR) models with different spline degrees of freedom and transformation expressions to summarize 492 longitudinal measurements for individual RUS bones scores assessed from 99 male academy student-athletes (chronological age range, 11.4 to 18 years; annual screening range, four to seven visits). RESULTS: The SITAR model with 5 degrees of freedom and untransformed chronological age was superior to the other models. The mean growth curve increased with age and showed a mid-pubertal double-kink at a RUS score of ~600 bone score units (au). The SITAR model revealed a first peak in the skeletal maturation velocity curve of ~206 au·year-1 occurred at ~13.5 years. The mean age at the second and largest peak occurred at 15.1 years (95% confidence interval [CI], 14.9 to 15.3 years), with the respective estimated peak skeletal ossification rate of 334 au·year-1 (95% CI, 290 to 377 au·year-1 ). The mean age at peak height velocity was 13.5 years (95% CI, 13.3 to 13.7 years), with peak height velocity of 10 cm·year-1 (95% CI, 9.6 to 10.4 cm·year-1 ). CONCLUSION: Application of the SITAR method confirmed two peaks in the skeletal maturation velocity curve, with the second and largest rate of ossification occurring at a relatively later timing of ~1.5 years than the height growth spurt. Knowledge of the RUS bones timing and intensity can be important to advance strategies for athlete performance development purposes.

A comparison of FELS and Tanner-Whitehouse II skeletal ages in male youth soccer players from the Middle East.

OBJECTIVES: To assess measurement agreement between FELS and Tanner-Whitehouse (TW) II skeletal ages in male youth soccer players from the Middle East. METHODS: We examined agreement between FELS and TW-II skeletal ages using data collected between- and within-subjects (n = 1057 observations) for 409 male, full-time, academy student-athletes recruited as part of the Qatar Football Association national soccer development programme (chronological age range, 9.8 to 18 years; annual screening range, one to seven visits). The Bland-Altman method for repeated measurements estimated the limits of agreement describing the expected range of differences for 95% of pairs of future FELS and TW-II skeletal ages determined on similar individuals from the reference population. RESULTS: The mean difference for TW-II versus FELS protocols was 0.02 years (95% confidence interval, -0.04 to 0.08 years) with lower and upper limits of agreement ranging from -1.39 years (95% confidence interval, -1.48 to -1.30 years) to 1.43 years (95% confidence interval, 1.34 to 1.52 years). CONCLUSION: Differences for 95% of pairs of future skeletal ages determined with FELS and TW-II methods in this population could be as high as ~3 years for some people that suggested protocols may not be interchangeable in youth Middle Eastern athletes. Justification of skeletal age protocol selection rests on knowledge of measurement bias and variability of expected growth estimations for rationalized application to a population of interest.

Subcutaneous choriocarcinomas in captive Amargosa voles (Microtus californicus scirpensis).

Spontaneous choriocarcinomas are rare, highly vascular, malignant trophoblastic tumors that occur in humans and animals. This report describes the unusual spontaneous presentation of 4 choriocarcinomas within the subcutaneous tissues of 4, multiparous but nongravid, Amargosa voles (Microtus californicus scirpensis) from a captive breeding colony. Two subcutaneous neoplasms were composed of multifocal discohesive and infiltrative aggregates of medium to large trophoblasts and cytotrophoblasts within a fibrovascular stroma. Neoplastic cells were associated with variably sized thrombi and cavitary areas of hemorrhage and necrosis. Two subcutaneous tumors were predominantly composed of expansile, blood-filled, cystic spaces lined by neoplastic cytotrophoblasts and occasionally contained medium to large trophoblasts. Trophoblasts and cytotrophoblasts were positive for pancytokeratin and cytokeratin 8/18, negative for alpha-fetoprotein, and contained intracytoplasmic Periodic acid-Schiff (PAS)-positive glycogen in all 4 tumors. In species with hemochorial placentation, migration of trophoblasts into maternal circulation with embolization to distant nonreproductive tissues occurs and may explain the unusual subcutaneous distribution of these 4 tumors. The 2 multiloculated paucicellular tumors may represent an early stage of neoplastic transformation. To the authors' knowledge, this is the first report characterizing choriocarcinomas in extrareproductive sites in rodents.

The Percentage of Mature Height as a Morphometric Index of Somatic Growth: A Formal Scrutiny of Conventional Simple Ratio Scaling Assumptions.

PURPOSE: To assess conventional assumptions that underpin the percentage of mature height index as the simple ratio of screening height (numerator) divided by actual or predicted adult height (denominator). METHODS: We examined cross-sectional data from 99 academy youth soccer players (chronological age range, 11.5 to 17.7 y) skeletally immature at the screening time and with adult height measurements available at follow-up. RESULTS: The y-intercept value of -60 cm (95% confidence interval, -115 to -6 cm) from linear regression between screening height and adult height indicated the failure to meet the zero y-intercept assumption. The correlation coefficient between present height and adult height of .64 (95% confidence interval, .50 to .74) was not equal to the ratio of coefficient of variations between these variables (CVx/CVy = 0.46) suggesting Tanner's special circumstance was violated. The non-zero correlation between the ratio and the denominator of .21 (95% confidence interval, .01 to .39) indicated that the percentage of mature height was biased low for players with generally shorter adult height, and vice versa. CONCLUSION: For the first time, we have demonstrated that the percentage of mature height is an inconsistent statistic for determining the extent of completed growth, leading to potentially biased inferences for research and applied purposes.

Eccentric hamstring strength in young athletes is best documented when normalised to body mass: A cross-sectional study with normative data of 590 athletes from different age categories.

Despite its widespread use in adults, the Nordic hamstring exercise remains underexplored in athletic youth populations. Further, given the dynamic nature of growth and maturation, comparisons with elite adult populations may be inaccurate. Here we describe absolute and body mass-normalised eccentric hamstring normative values for football, athletics and multi-sport youth populations. 676 routine standardised tests were conducted, including 244 U12-U18 student-athletes (football, athletics, multi-sport) and 346 Qatar Stars League (QSL) football players using the NordBord. The average maximum values for the left and right leg from 3 repetitions were recorded. Significant increases in absolute strength were seen across chronological (e.g., 150 N ± 15 for U12 to 330 N ± 40 for U18) and skeletal (142.9 N ± 13.9 for skeletal age of 12 compared to 336.2 N ± 71.2 for skeletal age of 18) age groups. The differences in values normalised to body mass were smaller at 3.6 N/kg ± 0.25 for the U-13 group, but similar for the U14 to U18 groups (4.5 N/kg ± 0.16, 4.6 N/kg ± 0.11, 4.6 N/kg ± 0.27, 4.7 N/kg ± 0.14, 4.5 N/kg ± 0.18). Students displayed lower absolute strength than the professional football players (272.1 N compared to 297.3 N, p < 0.0001) but higher relative strength (4.7 N/kg compared to 4.2 N/kg, p < 0.0001). Comparing Nordic hamstring strength values between athletes, and between skeletal and chronological age groups can be done when values are normalised to the athlete's body mass. For the U14s and onwards age categories, body mass normalised values are comparable to professional football players.

Gynecologist Supply Deserts Across the VA and in the Community.

BACKGROUND: The Veterans Health Administration (VA) refers patients to community providers for specialty services not available on-site. However, community-level specialist shortages may impede access to care. OBJECTIVE: Compare gynecologist supply in veterans' county of residence versus at their VA site. DESIGN: We identified women veteran VA patients from fiscal year (FY) 2017 administrative data and assessed availability of a VA gynecologist within 50 miles (hereafter called "local") of veterans' VA homesites (per national VA organizational survey data). For the same cohort, we then assessed community-level gynecologist availability; counties with < 2 gynecologists/10,000 women (per the Area Health Resource File) were "inadequate-supply" counties. We examined the proportion of women veterans with local VA gynecologist availability in counties with inadequate versus adequate gynecologist supply, stratified by individual and VA homesite characteristics. Chi-square tests assessed statistical differences. PARTICIPANTS: All women veteran FY2017 VA primary care users nationally. MAIN MEASURES: Availability of a VA gynecologist within 50 miles of a veteran's VA homesite; county-level "inadequate-supply" of gynecologists. KEY RESULTS: Among 407,482 women, 9% were in gynecologist supply deserts (i.e., lacking local VA gynecologist and living in an inadequate-supply county). The sub-populations with the highest proportions in gynecologist supply deserts were rural residents (24%), those who got their primary care at non-VAMC satellite clinics (13%), those who got their care at a site without a women's clinic (13%), and those with American Indian or Alaska Native (12%), or white (12%) race. Among those in inadequate-supply counties, 59.9% had gynecologists at their local VA; however, 40.1% lacked a local VA gynecologist. CONCLUSIONS: Most veterans living in inadequate-supply counties had local VA gynecology care, reflecting VA's critical role as a safety net provider. However, for those in gynecologist supply deserts, expanded transportation options, modified staffing models, or tele-gynecology hubs may offer solutions to extend VA gynecology capacity.

Prevalence and Impact of Obesity in a Population-Based Cohort of Patients With Crohn's Disease.

BACKGROUND: Obesity is on the rise within the inflammatory bowel disease population. The impact obesity has on the natural history of Crohn's disease (CD) is not well-understood. We aimed to describe the prevalence of obesity in a population-based cohort of newly diagnosed patients with CD, and the impact obesity had on disease phenotype and outcomes of corticosteroid use, hospitalization, intestinal resection, and development of fistulizing or penetrating disease. MATERIALS AND METHODS: A chart review was performed on Olmsted County, Minnesota residents diagnosed with CD between 1970 and 2010. Data were collected on demographics, body mass index, CD location and behavior, CD-related hospitalizations, corticosteroid use, and intestinal resection. The proportion of individuals considered obese at the time of CD diagnosis was evaluated over time, and CD-associated complications were assessed with Kaplan-Meier survival analysis. RESULTS: We identified 334 individuals diagnosed with CD between 1970 and 2010, of whom 156 (46.7%) were either overweight (27.8%) or obese (18.9%) at the time of diagnosis. The proportion of patients considered obese at the time of their diagnosis of CD increased 2-3 fold over the course of the study period. However, obesity did not have a significant impact on the future risk of corticosteroid use, hospitalization, intestinal resection, or development of penetrating and stricturing complications. CONCLUSIONS: Obesity is on the rise in patients with CD, although in this cohort, there did not appear to be any negative association with future CD-related outcomes. Further prospective studies, ideally including obesity measures such as visceral adipose tissue assessment, are warranted to understand the implications of the rising prevalence of obesity on CD outcomes.

Common and Not-So-Common Pathologic Findings of the Gastrointestinal Tract of Rhesus and Cynomolgus Macaques.

Rhesus and cynomolgus macaques are the most frequently used nonhuman primate (NHP) species for biomedical research and toxicology studies of novel therapeutics. In recent years, there has been a shortage of laboratory macaques due to a variety of competing factors. This was most recently exacerbated by the surge in NHP research required to address the severe acute respiratory syndrome (SARS)-coronavirus 2 pandemic. Continued support of these important studies has required the use of more varied cohorts of macaques, including animals with different origins, increased exposure to naturally occurring pathogens, and a wider age range. Diarrhea and diseases of the gastrointestinal tract are the most frequently occurring spontaneous findings in macaques of all origins and ages. The purpose of this review is to alert pathologists and scientists involved in NHP research to these findings and their impact on animal health and study endpoints, which may otherwise confound the interpretation of data generated using macaques.