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Background: Many different clinical specialists provide care to patients with Turner syndrome (TS), who have highly variable clinical manifestations. Therefore, a national TS registry is essential to inform a cohesive approach to healthcare and research. In 2015, the Turner Syndrome Society of the United States (TSSUS) created the Turner Syndrome Research Registry (TSRR) to engage directly with community participants who voluntarily provide longitudinal data about their experiences with TS. TSRR projects are collaborative partnerships between people with TS, TSSUS, and researchers. Results: To ensure that registry workflows conform to the data privacy choices of participants, TSSUS collaborated with UTHealth Houston in 2021 to create a new version of the TSRR that completely separates participant health data (stored at UTHealth) and personal identifiers (maintained at TSSUS). We developed an innovative Visual Basic (VB) script that, when embedded into Microsoft Outlook, redirects REDCap surveys through TSSUS to participants by matching registry IDs to participant email addresses. Additionally, the utilization of REDCap allows for portability of data as it is an open source platform. Conclusion: In this report, we will highlight three recent changes that more closely align the TSRR with this mission: a unique and equal collaborative partnership between UTHealth and TSSUS, an open-source platform, REDCap, that ensures data portability and compatibility across institutions, and an innovative survey routing system that retains participant confidentiality without sacrificing REDCap survey distribution capabilities to connect researchers with thousands of participants. [ABSTRACT FROM AUTHOR]

Background: The combination of prophylactic pancreatic stent placement (PSP) - a temporary plastic stent placed in the pancreatic duct - and rectal non-steroidal anti-inflammatory drugs (NSAIDs) is recommended for preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk cases. Preliminary data, however, suggest that PSP may be unnecessary if rectal NSAIDs are administered. Given the costs and potential risks of PSP, we aim to determine whether rectal indomethacin obviates the need for pancreatic stent placement in patients undergoing high-risk ERCP.Methods/design: The SVI (Stent vs. Indomethacin) trial is a comparative effectiveness, multicenter, randomized, double-blind, non-inferiority study of rectal indomethacin alone versus the combination of rectal indomethacin and PSP for preventing PEP in high-risk cases. One thousand four hundred and thirty subjects undergoing high-risk ERCP, in whom PSP is planned solely for PEP prevention, will be randomized to indomethacin alone or combination therapy. Those who are aware of study group assignment, including the endoscopist, will not be involved in the post-procedure care of the patient for at least 48 hours. Subjects will be assessed for PEP and its severity by a panel of independent and blinded adjudicators. Indomethacin alone will be declared non-inferior to combination therapy if the two-sided 95 % upper confidence bound of the treatment difference is less than 5 % between the two groups. Biological specimens will be obtained from trial participants and centrally banked.Discussion: The SVI trial is designed to determine whether PSP remains necessary in the era of NSAIDs pharmacoprevention. The associated bio-repository will establish the groundwork for important scientific breakthrough.Trial Registration: NCT02476279, registered June 2015. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]

Background: In South Africa, pervasive age and gender inequities have been exacerbated by the COVID-19 pandemic and public health response. We aimed to explore experiences of the COVID-19 pandemic among youth in eThekwini district, South Africa., Methods: Between December 2021-May 2022 we explored experiences of the COVID-19 pandemic on youth aged 16-24 residing in eThekwini, South Africa. We collated responses to the open-ended question "Has the COVID-19 pandemic affected you in any other way you want to tell us about?" in an online survey focused on understanding the pandemic's multi-levelled health and social effects. We used a thematic analysis to summarise the responses., Results: Of 2,068 respondents, 256 (12.4%, median age = 22, 60.9% women) completed the open-ended survey question (11% in isiZulu). Results were organized into three main themes encompassing (1) COVID-19-related loss, fear, grief, and exacerbated mental and physical health concerns; (2) COVID-19-related intensified hardships, which contributed to financial, employment, food, education, and relationship insecurities for individuals and households; and (3) positive effects of the pandemic response, including the benefits of government policies and silver linings to government restrictions., Conclusions: We found that South African youth experienced significant grief and multiple losses (e.g., death, income, job, and educational) during the COVID-19 pandemic. Trauma-aware interventions that provide economic and educational opportunities must be included in post-COVID recovery efforts., (© 2024. The Author(s).)

Background: Federally Qualified Health Centers (FQHCs) are a critical source of care for medically underserved populations and often serve as medical homes for individuals with serious mental illness (SMI). Many FQHCs provide mental health services and could facilitate access to mental health treatment within and outside of FQHCs. This study compared mental health care utilization and acute care events for adult Medicaid enrollees with SMI who receive care at Federally Qualified Health Centers (FQHCs) vs. other settings., Methods: This study used the 2015-2016 Massachusetts All-Payer Claims Database to examine outpatient mental health care and acute care events for 32,330 Medicaid adults, ages 18-64 and with major depressive, bipolar, or schizophrenia spectrum disorders (SSD), who resided in FQHC service areas and received care from FQHCs vs. other settings in 2015. Multivariable linear regressions assessed associations between receiving care at FQHCs and outpatient mental health visits, psychotropic medication fills, and acute care events in 2016., Results: There were 8,887 (27.5%) adults in the study population (N = 32,330) who had at least one FQHC visit in 2015. Those who received care at FQHCs were more likely to have outpatient mental health visits (73.3% vs. 71.2%) and psychotropic medication fills (73.2% vs. 69.0%, both p < .05), including antidepressants among those with depressive disorders and antipsychotics among those with SSD. They were more likely to have ED visits (74.0% vs. 68.7%), but less likely to be hospitalized (27.8% vs. 31.9%, both p < .05). However, there was no significant difference in the likelihood of having an acute psychiatric hospitalization (9.5% vs. 9.8%, p = .35)., Conclusions: Among Medicaid enrollees with SMIs who had access to care at FQHCs, those receiving care at FQHCs were more likely to have outpatient mental health visits and psychotropic medication fills, with lower rates of hospitalization, suggesting potentially improved quality of outpatient care. Higher ED visit rates among those receiving care at FQHCs warrant additional investigation., (© 2024. The Author(s).)

Though we have made ample advances in the field of medicine in recent years, our idea of professionalism continues to be based on the standard of how white men dressed in the nineteenth century. Such a standard of professionalism not only perpetuates gender bias, but also aims to remove the culture, traditions, and behaviors of minority groups with the goal of molding these individuals to resemble the majority, preventing 'Afro' heritage from entering medicine. By contextualizing our own experiences in the medical setting as physicians of color in the context of a variety of supporting literature, we provide an overview of professionalism, its role in medicine, the double standard faced by women, and how it continues to be weaponized against physicians of racial, ethnic, and religious minorities. We advocate for minority physicians to embrace their authenticity and for institutions to develop policies that openly, firmly, and enthusiastically welcome physicians of all ethnicities, religions, and genders. Positionality Statement: In the editorial you are about to read, we, the authors, collectively bring a rich tapestry of backgrounds and experiences to our discussion on healthcare disparities. Our team consists of two Hispanic/Latina oncologists, one Middle Eastern oncologist, one Black/Caribbean-American hematologist, and one White pre-medical student with Middle Eastern heritage. Our diverse backgrounds inform our perspectives and enhance our understanding of the complex and multifaceted nature of healthcare. We are united by a shared commitment to justice, equity, and the belief that every patient deserves high-quality care, regardless of their background. This editorial is informed by our professional expertise, personal experiences, and the diverse communities we serve, aiming to highlight the critical need for inclusivity and representation in healthcare. By acknowledging our positionality, we hope to provide a comprehensive and empathetic analysis that not only identifies the challenges but also offers actionable solutions to improve healthcare outcomes for all. We recognize the power of diversity in fostering innovation and driving positive change, and we are dedicated to using our voices and positions to advocate for a more equitable healthcare system., (© 2024. The Author(s).)

Purpose: Transdisciplinarity has been described as a fusion of theories, methods, and expertise across disciplinary boundaries to address complex, global problems. This approach has coincided with an increase in US medical schools offering masters degrees along with an MD degree to equip medical students to practice in complex, interconnected health systems. This study focused on medical schools that graduate the most dual degree students per year and explored the alignment of such programs with a transdisciplinary approach., Methods: We identified 19 allopathic medical schools that annually graduated an average of 10 or more dual-degree students from 2015-2020. We surveyed these schools and asked participants to describe the reason(s) their institutions offered dual-degree programs. Two authors coded the narrative responses from the survey., Results: Responses were received from 17 of the 19 schools. The analysis of participants' responses regarding their institutions' purpose for offering dual programs revealed several themes associated with a transdisciplinary approach to training. The most common themes were expand skill sets beyond a medical degree (73%), provide opportunity for interdisciplinary collaboration (67%), expand career interest and goals (60%), develop leaders (53%), enhance residency applications (47%) and further the institution's vision and mission (45%)., Conclusions: This study is the first comprehensive evaluation of MD/Masters programs in the United States that includes a summary of the medical schools with the largest dual degree programs and their reasons for offering them. The findings support the hypothesis that allopathic medical schools recognize the need for a transdisciplinary approach to prepare students for the complexities in healthcare. These programs provide students with opportunities for additional areas of expertise, leadership development, enhancement of competitiveness for residency application, and interdisciplinary collaboration. Medical schools without dual-degree programs may consider developing these programs to provide benefits to students and institutions., (© 2024. The Author(s).)

Introduction: Non-nursing tasks (NNTs) have become a prevalent issue among healthcare professionals, affecting nurses globally. This study delves into the experiences of Jordanian nurses regarding NNTs, aiming to uncover challenges and propose solutions within the Jordanian healthcare context., Objective: Explore the impact of NNTs on Jordanian nurses' roles, workload, and satisfaction. Additionally, the study aims to identify various types of NNTs performed by nurses, understand their impact, and propose solutions to mitigate challenges associated with these tasks., Methods: A qualitative-exploratory research design was employed for this study. Semi-structured interviews were conducted with Jordanian nurses using a purposeful sampling approach to ensure a diverse representation of experiences and perspectives. Thematic analysis was used to identify recurring themes and patterns related to NNTs, their challenges, and potential solutions. Ethical guidelines were strictly followed to maintain participant confidentiality and ensure the integrity of the data collected., Results: Analysis of the interviews revealed four major themes: challenges of NNTs, types of NNTs, impact of NNTs, and proposed solutions. Nurses faced significant difficulties due to task ambiguity, role confusion, and increased workload from NNTs, which included administrative duties, clerical work, and tasks typically performed by other healthcare professionals. These NNTs negatively impacted nurses' effectiveness, productivity, and job satisfaction by diverting time and energy from primary nursing responsibilities, causing professional strain. To address these issues, participants suggested clearer job descriptions, stricter task assignment protocols, and systemic changes to tackle the root causes of NNTs., Conclusion: This study sheds light on the pervasive challenges posed by NNTs among Jordanian nurses and emphasizes the importance of addressing these issues to enhance nursing care quality and nurse well-being. By proposing actionable solutions tailored to the Jordanian context, this research contributes to the global discourse on NNTs and underscores the need for organizational support and advocacy to optimize nurses' roles and improve patient care outcomes., (© 2024. The Author(s).)

Background: Experiences during the birth hospitalization affect a family's ability to establish and maintain breastfeeding. The Ten Steps to Successful Breastfeeding (Ten Steps) describe evidence-based hospital policies and practices shown to improve breastfeeding outcomes. We aim to describe hospitals' implementation of the Ten Steps, changes over time, and hospitals' implementation of a majority (≥ 6) of the Ten Steps by hospital characteristics and state., Methods: The biennial Maternity Practices in Infant Nutrition and Care (mPINC) survey assesses all hospitals in the United States (including the District of Columbia and territories) that routinely provide maternity care services. We analyzed data from 2018, 2020, and 2022 survey cycles to describe trends in the prevalence of hospitals implementing maternity care policies and practices that are consistent with the Ten Steps. Differences were calculated using the absolute difference in percentage-points between 2018 and 2022., Results: Between 2018 and 2022, the percentage of hospitals that implemented Step 2: Staff Competency and Step 5: Support Mothers with Breastfeeding increased 12 and 8 percentage points, respectively. The percentage of hospitals that implemented Step 6: Exclusive Breastfeeding Among Breastfed Infants was 7 percentage points lower in 2022 than 2018. Implementation of the remaining seven steps did not change by more than 5 percentage points in either direction between 2018 and 2022. Nationally, the percentage of hospitals that implemented ≥ 6 of the Ten Steps increased from 44.0% in 2018 to 51.1% in 2022. Differences were seen when comparing implementation of ≥ 6 of the Ten Steps by hospital characteristics including state, hospital size, and highest level of neonatal care offered., Conclusions: Nationally, maternity care policies and practices supportive of breastfeeding continued to improve; however, certain practices lost progress. Differences in implementation of the Ten Steps were observed across states and by certain hospital characteristics, suggesting more work is needed to ensure all people receive optimal breastfeeding support during their delivery hospitalization., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Growing evidence suggests that chronic inflammation caused by tuberculosis (TB) may increase the incidence of diabetes. However, the relationship between post-TB pulmonary abnormalities and diabetes has not been well characterized., Methods: We analyzed data from a cross-sectional study in KwaZulu-Natal, South Africa, of people 15 years and older who underwent chest X-ray and diabetes screening with hemoglobin A1c testing. The analytic sample was restricted to persons with prior TB, defined by either (1) a self-reported history of TB treatment, (2) radiologist-confirmed prior TB on chest radiography, and (3) a negative sputum culture and GeneXpert. Chest X-rays of all participants were evaluated by the study radiologist to determine the presence of TB lung abnormalities. To assess the relationships between our outcome of interest, prevalent diabetes (HBA1c ≥6.5%), and our exposure of interest, chest X-ray abnormalities, we fitted logistic regression models adjusted for potential clinical and demographic confounders. In secondary analyses, we used the computer-aided detection system CAD4TB, which scores X-rays from 10 to 100 for detection of TB disease, as our exposure interest, and repeated analyses with a comparator group that had no history of TB disease., Results: In the analytic cohort of people with prior TB (n = 3,276), approximately two-thirds (64.9%) were women, and the average age was 50.8 years (SD 17.4). The prevalence of diabetes was 10.9%, and 53.0% of people were living with HIV. In univariate analyses, there was no association between diabetes prevalence and radiologist chest X-ray abnormalities (OR 1.23, 95%CI 0.95-1.58). In multivariate analyses, the presence of pulmonary abnormalities was associated with an 29% reduction in the odds of prevalent diabetes (aOR 0.71, 95%CI 0.53-0.97, p = 0.030). A similar inverse relationship was observed for diabetes with each 10-unit increase in the CAD4TB chest X-ray scores among people with prior TB (aOR 0.92, 95%CI 0.87-0.97; p = 0.002), but this relationship was less pronounced in the no TB comparator group (aOR 0.96, 95%CI 0.94-0.99)., Conclusions: Among people with prior TB, pulmonary abnormalities on digital chest X-ray are inversely associated with prevalent diabetes. The severity of radiographic post-TB lung disease does not appear to be a determinant of diabetes in this South African population., (© 2024. The Author(s).)

Background: Studies of animal habitat selection are important to identify and preserve the resources species depend on, yet often little attention is paid to how habitat needs vary depending on behavioral state. Fishers (Pekania pennanti) are known to be dependent on large, mature trees for resting and denning, but less is known about their habitat use when foraging or moving within a home range., Methods: We used GPS locations collected during the energetically costly pre-denning season from 12 female fishers to determine fisher habitat selection during two critical behavioral activities: foraging (moving) or resting, with a focus on response to forest structure related to past forest management actions since this is a primary driver of fisher habitat configuration. We characterized behavior based on high-resolution GPS and collar accelerometer data and modeled fisher selection for these two behaviors within a home range (third-order selection). Additionally, we investigated whether fisher use of elements of forest structure or other important environmental characteristics changed as their availability changed, i.e., a functional response, for each behavior type., Results: We found that fishers exhibited specialist selection when resting and generalist selection when moving, with resting habitat characterized by riparian drainages with dense canopy cover and moving habitat primarily influenced by the presence of mesic montane mixed conifer forest. Fishers were more tolerant of forest openings and other early succession elements when moving than resting., Conclusions: Our results emphasize the importance of considering the differing habitat needs of animals based on their movement behavior when performing habitat selection analyses. We found that resting fishers are more specialist in their habitat needs, while foraging fishers are more generalist and will tolerate greater forest heterogeneity from past disturbance., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: In Latin America, interventions aimed at adolescents' health suffer from a shortfall of investment and lack of sustainability. Nurses, as an integral part of health services and systems, can lead the implementation and development of public health policies to improve adolescent health., Objective: To identify and analyze the role of nurses in the development and implementation of public policies and in the provision of health care to adolescents in Colombia, Ecuador, and Peru., Methods: The research was carried out in three phases: a documentary analysis, an online survey, and semi-structured focus groups. A total of 48 documents were analyzed, 288 nurses participated in the survey, and 29 nurses participated in the focus groups., Results: State policies aim to guarantee rights, with special protection for children and adolescents. It is an incremental process, with greater involvement of civil society and governments. Participants reported a lack of synergy between law and practice, as well as differences in regulatory compliance in rural areas and in populations of different ethnicities and cultures. Their perception was that the protection of adolescents is not specifically enshrined in the legal bases and regulatory structures of the countries, meaning that there are both protective factors and tensions in the regulatory framework. While nurses are highly committed to different actions aimed at adolescents, their participation in policy development and implementation is low, with barriers related to a lack of specialized training and working conditions., Conclusions: Given nurses' involvement in different actions aimed at adolescents, they could play a fundamental role in the development of policies for adolescents and ensure their effective implementation. Policymakers should consider revising the budget to make compliance viable, incorporating and using monitoring indicators, and increasing the involvement of educational institutions and the community., (© 2024. The Author(s).)

In their article on "Navigating the Field of Implementation Science Towards Maturity: Challenges and Opportunities," Chambers and Emmons describe the rapid growth of implementation science along with remaining challenges. A significant gap remains in training and capacity building. Formats for capacity building include university degree programs, summer training institutes, workshops, and conferences. In this letter, we describe and amplify on five key areas, including the need to (1) identify advanced competencies, (2) increase the volume and reach of trainings, (3) sustain trainings, (4) build equity focused trainings, and (5) develop global capacity. We hope that the areas we highlight will aid in addressing several key challenges to prioritize in future efforts to build greater capacity in implementation science., (© 2024. The Author(s).)

Background: Obstructive sleep apnea (OSA) was associated with the increased cardiovascular events and all-cause mortality. And anti-inflammatory dietary has potential to improve the prognosis of OSA. This study aimed to investigate the association of anti-inflammatory dietary patterns with all-cause mortality among individuals with OSA., Methods: This retrospective cohort study involved 1522 older adults with OSA from 2005 to 2008 in the National Health and Nutrition Examinations Survey (NHANES). Mortality status was determined by routine follow-up through December 31, 2019, using the National Death Index. Anti-inflammatory dietary patterns included Alternate Mediterranean Diet Score (aMED), Healthy Eating Index-2015 (HEI-2015), and Alternate Healthy Eating Index-2010 (AHEI-2010). Weighted Cox proportional hazard regression models were performed to investigate the association between anti-inflammatory dietary pattern and all-cause mortality., Results: After a median follow-up of 131 months, 604 participants were recorded all-cause mortality. The mean age of OSA patients was 68.99 years old, of whom 859 were male (52.34%). Higher adherence of aMED (HR = 0.61, 95%CI: 0.48 to 0.78) and HEI-2015 (HR = 0.75, 95%CI: 0.60 to 0.95) were associated with lower all-cause mortality risk in the elderly with OSA. Conversely, no association was found between AHEI-2010 dietary pattern and all-cause mortality in individuals with OSA. In the component analysis of aMED, it was found that a higher intake of vegetables and olive oil potentially contributes to the reduction all-cause mortality risk in the elderly with OSA (HR = 0.60, 95%CI: 0.48 to 0.76; HR = 0.67, 95%CI: 0.63 to 0.71)., Conclusion: Higher adherence to the aMED and the HEI-2015 was associated with a lower risk of all-cause mortality in OSA. Future interventions in the elderly with OSA should considering adopting anti-inflammatory dietary patterns., (© 2024. The Author(s).)

Background: The purpose of this report is to provide insight and details regarding the development and implementation of an injury and illness surveillance (IIS) system for the United States Olympic and Paralympic Committee (USOPC)., Methods: The development and deployment of the IIS employed a multiphase approach. First, researchers determined variables to include in the IIS using the recommendations from the 2020 IOC consensus statement for reporting sport epidemiological data. Second, the hosting and deployment platforms were comprehensively evaluated for their suitability, ease of use, flexibility, and backend data structure (for both capture and aggregation). Third, focus groups consisting of the Sports Medicine department leadership and clinicians piloted the IIS system and revisions were made based on their feedback. Pilot testing of the IIS and follow-up focus groups were then conducted among all departmental clinicians to solicit additional feedback and drive further revisions. Finally, the IIS system was piloted among providers working during the 2023 Pan American and Parapan American Games to refine the system for future Games. After reviewing all potential software platform options (electronic medical record [EMR] system, athlete management systems, secure data collection platforms), Qualtrics (Qualtrics, Provo, UT, USA) was selected to host the IIS system. This choice was made due to the inability of the EMR and athlete-management systems to make frequent updates, modify existing questions, and provide the necessary form logic for the variety of scenarios in which the IIS system would be deployed. Feedback from the department's leadership and clinicians resulted in a number of changes, most notably being the ability to enter multiple diagnoses for a single injury event. Additionally, clinician feedback resulted in the creation of additional diagnostic codes not currently present in the OSIICS v14.0 diagnostic coding system, adding "non-sport" as an additional variable for injury setting, and developing a system for reporting return-to-sport date for time-loss injuries., Discussion: A multi-stage process of extensive planning, stakeholder feedback, and ongoing updates is required in order to successfully develop and implement an IIS system within a National Olympic and Paralynpic Committee. This process can be used to inform the development and implementation of IIS systems in other sporting organizations., (© 2024. The Author(s).)

An under-recognised aspect of the current humanitarian catastrophe in Gaza is the impact of the war on the environment and the associated risks for human health. This commentary contextualises these impacts against the background of human suffering produced by the overwhelming violence associated with the use of military force against the general population of Gaza. In calling for an immediate cessation to the violence, the authors draw attention to the urgent need to rebuild the health care system and restore the physical and human infrastructure that makes a liveable environment possible and promotes human health and well-being, especially for the most vulnerable in the population. Environmental remediation should therefore form one of the most important parts of international efforts to assist reconstruction, through which we hope Palestinians and Israelis will achieve lasting peace, health, and sustainable development, all as part of accepted international human rights obligations., (© 2024. The Author(s).)

Background: Peer mentorship can be a potential tool to reduce the disparities in health research capacity between high- and low- and middle-income countries. This case study describes the potential of peer mentorship to tackle two critical issues: bridging health research capacity of doctors from low- and middle-income countries (LMICs) and the transformation of human resource for health brain drain into "brain gain"., Case Presentation: In 2021, a virtual peer mentorship group was established by 16 alumni of the University of Benin College of Medical Sciences' 2008 graduating class, residing across three continents. This program aimed to facilitate research collaboration and skill development among colleagues with diverse research experience levels, fostering a supportive environment for career development in research. The group relied heavily on digital technology to carry out its activities due to the different geographical locations of the group members. Led by experienced peer leaders, the group fostered a collaborative learning environment where members leveraged each other's expertise. Within 18 months, we published two research papers in high-impact peer-reviewed global health journals, launched a mixed-methods research study, and conducted training sessions on research design and implementation. Findings from our work were presented at conferences and workshops. However, logistical hurdles, competing priorities, structural constraints, and uneven participation presented challenges., Conclusion: The peer mentorship collaboration has achieved some successes so far, and this model can be emulated by other cohorts of medical professionals across LMICs. Despite the group's success at a micro- or individual level, there remain significant structural barriers to research capacity building in LMICs that can only be addressed at the meso- and macro-levels by institutions and government, respectively. A systems-level approach is required to develop and support research capacity building and foster global research collaboration and effectively turn brain drain into brain gain., (© 2024. The Author(s).)

Background: In oral squamous cell carcinoma (OSCC), the tumor-node-metastasis (TNM) staging system is a significant factor that influences prognosis and treatment decisions for OSCC patients. Unfortunately, TNM staging does not consistently predict patient prognosis and patients with identical clinicopathological characteristics may have vastly different survival outcomes. Host immunity plays an important role in tumor progression but is not included in the TNM staging system. Tumor-infiltrating lymphocytes (TILs) are part of the host immune response that recognizes tumor cells; and the presence of TILs has emerged as potential candidates for prognostic markers for many types of cancers. The present study aims to determine the association of T cell-specific markers (CD3, CD4, CD8, and FOXP3) with clinicopathological characteristics and survival outcomes in OSCC patients. The prognostic value of CD3, CD4, and CD8 will also be evaluated based on tumor stage., Methods: Tissue microarrays were constructed containing 231 OSCC cases and analyzed by immunohistochemical staining for the expression of CD3, CD4, CD8, and FOXP3. The expression scores for each marker were correlated with clinicopathological parameters and survival outcomes. The prognostic impact of CD3, CD4 and CD8 were further analyzed based on tumor stage (early or advanced)., Results: CD3, CD4, and CD8 were found to be significantly associated with both overall survival and progression-free survival using univariate analysis. However, none of these markers were found to independently predict the survival outcomes of OSCC using multivariate analysis. Only conventional factors such as nodal status, tumor differentiation and perineural invasion (PNI) were independent predictors of survival outcomes, with nodal status being the strongest independent predictor. Additionally, low CD4 (but not CD3 or CD8) expression was found to identify early-stage OSCC patients with exceptionally poor prognosis which was similar to that of advanced staged OSCC patients., Conclusions: TIL markers such as CD3, CD4, CD8, and FOXP3 can predict the survival outcomes of OSCC patients, but do not serve as independent prognostic markers as found with conventional factors (i.e. nodal status, tumor differentiation and PNI). CD4 expression may assist with risk stratification in early-stage OSCC patients which may influence treatment planning and decision making for early-stage OSCC patients., (© 2024. The Author(s).)

Background: The incidence of myocardial infarction (MI) and sudden cardiac death (SCD) is significantly higher in individuals with Type 2 Diabetes Mellitus (T2DM) than in the general population. Strategies for the prevention of fatal arrhythmias are often insufficient, highlighting the need for additional non-invasive diagnostic tools. The T-wave heterogeneity (TWH) index measures variations in ventricular repolarization and has emerged as a promising predictor for severe ventricular arrhythmias. Although the EMPA-REG trial reported reduced cardiovascular mortality with empagliflozin, the underlying mechanisms remain unclear. This study investigates the potential of empagliflozin in mitigating cardiac electrical instability in patients with T2DM and coronary heart disease (CHD) by examining changes in TWH., Methods: Participants were adult outpatients with T2DM and CHD who exhibited TWH > 80 µV at baseline. They received a 25 mg daily dose of empagliflozin and were evaluated clinically including electrocardiogram (ECG) measurements at baseline and after 4 weeks. TWH was computed from leads V4, V5, and V6 using a validated technique. The primary study outcome was a significant (p < 0.05) change in TWH following empagliflozin administration., Results: An initial review of 6,000 medical records pinpointed 800 patients for TWH evaluation. Of these, 412 exhibited TWH above 80 µV, with 97 completing clinical assessments and 90 meeting the criteria for high cardiovascular risk enrollment. Empagliflozin adherence exceeded 80%, resulting in notable reductions in blood pressure without affecting heart rate. Side effects were generally mild, with 13.3% experiencing Level 1 hypoglycemia, alongside infrequent urinary and genital infections. The treatment consistently reduced mean TWH from 116 to 103 µV (p = 0.01)., Conclusions: The EMPATHY-HEART trial preliminarily suggests that empagliflozin decreases heterogeneity in ventricular repolarization among patients with T2DM and CHD. This reduction in TWH may provide insight into the mechanism behind the decreased cardiovascular mortality observed in previous trials, potentially offering a therapeutic pathway to mitigate the risk of severe arrhythmias in this population., Trial Registration: NCT: 04117763., (© 2024. The Author(s).)

Aims: This study sought to develop and assess an exploratory model of how demographic and psychosocial attributes, and drug use or acquisition behaviors interact to affect opioid-involved overdoses., Design: We conducted exploratory and confirmatory factor analysis (EFA/CFA) to identify a factor structure for ten drug acquisition and use behaviors. We then evaluated alternative structural equation models incorporating the identified factors, adding demographic and psychosocial attributes as predictors of past-year opioid overdose., Setting and Participants: We used interview data collected for two studies recruiting opioid-misusing participants receiving services from a community-based syringe services program. The first investigated current attitudes toward drug-checking (N = 150). The second was an RCT assessing a telehealth versus in-person medical appointment for opioid use disorder treatment referral (N = 270)., Measurements: Demographics included gender, age, race/ethnicity, education, and socioeconomic status. Psychosocial measures were homelessness, psychological distress, and trauma. Self-reported drug-related risk behaviors included using alone, having a new supplier, using opioids with benzodiazepines/alcohol, and preferring fentanyl. Past-year opioid-involved overdoses were dichotomized into experiencing none or any., Findings: The EFA/CFA revealed a two-factor structure with one factor reflecting drug acquisition and the second drug use behaviors. The selected model (CFI = .984, TLI = .981, RMSEA = .024) accounted for 13.1% of overdose probability variance. A latent variable representing psychosocial attributes was indirectly associated with an increase in past-year overdose probability (β = .234, p = .001), as mediated by the EFA/CFA identified latent variables: drug acquisition (β = .683, p < .001) and drug use (β = .567, p = .001). Drug use behaviors (β = .287, p = .04) but not drug acquisition (β = .105, p = .461) also had a significant, positive direct effect on past-year overdose. No demographic attributes were significant direct or indirect overdose predictors., Conclusions: Psychosocial attributes, particularly homelessness, increase the probability of an overdose through associations with risky drug acquisition and drug-using behaviors. Further research is needed to replicate these findings with populations at high-risk of an opioid-related overdose to assess generalizability and refine the metrics used to assess psychosocial characteristics., (© 2024. The Author(s).)

Background: Physicians and associate (non-physician) clinicians conduct cesarean sections in Tanzania and Malawi. Urogenital fistulas may occur as complications of cesarean section. Location and circumstances can indicate iatrogenic origin as opposed to ischemic injury following prolonged, obstructed labor., Methods: This retrospective review assessed the frequency of iatrogenic urogenital fistulas following cesarean sections conducted by either associate clinicians or physicians in Tanzania and Malawi. It focuses on 325 women with iatrogenic fistulas among 1290 women who had fistulas after cesarean birth in Tanzania and Malawi between 1994 and 2017. An equivalence test compared the proportion of iatrogenic fistulas after cesarean sections performed by associate clinicians and physicians (equivalence margin = 0.135). Logistic regression was used to model the occurrence of iatrogenic fistula after cesarean section, controlling for cadre, date, maternal age, previous abdominal surgery and parity., Results: Associate clinicians attended 1119/1290 (86.7%) cesarean births leading to fistulas, while physicians attended 171/1290 (13.3%). Iatrogenic fistulas occurred in 275/1119 (24.6%) cesarean births by associate clinicians and in 50/171 (29.2%) cesarean births by physicians. The risk difference and 90% confidence interval were entirely contained within an equivalence margin of 13.5%, supporting a conclusion of equivalence between the two cadres. The odds of iatrogenic fistula after cesarean section were not statistically significantly different between associate clinicians and physicians (aOR 0.90; 95% CI 0.61-1.33)., Conclusions: Associate clinicians appear equivalent to physicians performing cesarean sections in terms of iatrogenic fistula risk. Lower iatrogenic proportions for associate clinicians could reflect different caseloads. The occurrence of iatrogenic fistulas illustrates the importance of appropriate labor management and cesarean section decision-making, irrespective of health provider cadre. Given the noninferior performance and lower costs of employing associate clinicians, other countries with insufficient and/or unequally distributed health workforces could consider task-shifting cesarean sections to associate clinicians., (© 2024. The Author(s).)

Background: Predictors of the outcome of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection remain to be fully determined. We evaluated selected viral characteristics and immunological responses that might predict and/or correlate to the clinical outcome of COVID-19., Methods: For individuals developing divergent clinical outcomes, the magnitude and breadth of T cell-mediated responses were measured within 36 h of symptom onset. Peripheral Blood Mononuclear Cells (PBMCs) were subjected to in vitro stimulation with SARS-CoV-2-based peptides. In addition, SARS-CoV-2 sequences were generated by metagenome, and HLA typing was performed using Luminex technology., Findings: CD4 + T cell activation was negatively correlated with SARS-CoV-2 basal viral load in patients with severe COVID-19 (p = 0·043). The overall cellular immune response, as inferred by the IFN-γ signal, was higher at baseline for patients who progressed to mild disease compared to patients who progressed to severe disease (p = 0·0044). Subjects with milder disease developed higher T cell responses for MHC class I and II-restricted peptides (p = 0·033)., Interpretation: Mounting specific cellular immune responses in the first days after symptom onset, as inferred by IFN-γ magnitude in the ELISPOT assay, may efficiently favor a positive outcome. In contrast, progression to severe COVID-19 was accompanied by stronger cellular immune responses, higher CD4 + T cell activation, and a higher number of in silico predicted high-affinity class I HLA alleles., (© 2024. The Author(s).)

Alternative splicing (AS) contributes to the biological heterogeneity between species, sexes, tissues, and cell types. Many diseases are either caused by alterations in AS or by alterations to AS. Therefore, measuring AS accurately and efficiently is critical for assessing molecular phenotypes, including those associated with disease. Long-read sequencing enables more accurate quantification of differentially spliced isoform expression than short-read sequencing approaches, and third-generation platforms facilitate high-throughput experiments. To assess differences in AS across the cerebellum, cortex, hippocampus, and striatum by sex, we generated and analyzed Oxford Nanopore Technologies (ONT) long-read RNA sequencing (lrRNA-Seq) C57BL/6J mouse brain cDNA libraries. From > 85 million reads that passed quality control metrics, we calculated differential gene expression (DGE), differential transcript expression (DTE), and differential transcript usage (DTU) across brain regions and by sex. We found significant DGE, DTE, and DTU across brain regions and that the cerebellum had the most differences compared to the other three regions. Additionally, we found region-specific differential splicing between sexes, with the most sex differences in DTU in the cortex and no DTU in the hippocampus. We also report on two distinct patterns of sex DTU we observed, sex-divergent and sex-specific, that could potentially help explain sex differences in the prevalence and prognosis of various neurological and psychiatric disorders in future studies. Finally, we built a Shiny web application for researchers to explore the data further. Our study provides a resource for the community; it underscores the importance of AS in biological heterogeneity and the utility of long-read sequencing to better understand AS in the brain., (© 2024. The Author(s).)

Introduction: Gender-based violence (GBV) is a major public health problem that disproportionately affects women. In Cameroon, as well as other countries worldwide, GBV has immediate effects on women's health, with one in three women experiencing physical or sexual violence from an intimate partner, affecting their physical and reproductive health. The objective of this study was to determine the health risks associated with GBV among women in Yaoundé., Methods: A cross-sectional study was conducted in Yaoundé (Cameroon), from August to October 2022. Adverse health outcome included mental disorders, physical trauma, gynaecological trauma, behavioral disorders, and any other disorder. Tests of associations were used to establish relationships between qualitative variables. Associations were further quantified using crude odds ratio (OR) for univariate analysis and adjusted odds ratio (aOR) for multivariate analysis with 95% confidence interval (CI). Independent variables included: Physical violence, Sexual violence, Economic violence, Emotional violence, Age, Number of children, and Marital status. Variables with p-value˂0.05 were considered statistically significant., Results: A total of 404 women aged 17 to 67 years were interviewed. Emotional violence was the most commonly reported violence (78.8%), followed by economic violence (56.9%), physical violence (45.8%) and sexual violence (33.7%). The main reasons for violence were jealousy (25.7%), insolence (19.3%) and the refusal to have sexual intercourse (16.3%). The prevalences of adverse health outcomes were physical trauma (90.9%), followed by mental disorders (70,5%), gynaecological trauma (38.4%), behavioral disorders (29.7%), and other (5.5%). Most victims reported at least one of the above-mentioned conditions (80.2%). Women who were victims of any kind of violence had a higher likelihood of experiencing adverse health outcomes: physical violence [OR = 34.9, CI(10.8-112.9), p < 0.001]; sexual violence [OR = 1.5, CI(0.9-2.7), p = 0.11]; economic violence [OR = 2.4, CI(1.4-3.9), p = 0.001]; and emotional violence [OR = 2.9, CI(1.7-4.9), p < 0.001]. Using multiple binary logistic regression, only physical violence [aOR = 15.4, CI(6.7-22.5), p = 0.001] remained highly associated with an increased likelihood of having adverse health outcomes., Conclusion: This study underscores the urgent need for comprehensive interventions to address GBV, including improved reporting and documentation of cases, increased awareness among healthcare providers, the establishment of support networks for victims, primary and secondary prevention of GBV. It is essential that the Government of Cameroon, through the Ministries in charge of Health and Women's Empowerment, minimizes the health effects of GBV through early identification, monitoring, and treatment of GBV survivors by providing them with high-quality health care services., (© 2024. The Author(s).)

Background: Adherence to antiretroviral therapy (ART) has individual and public health benefits and is critical to improving life expectancy, achieving viral suppression, and reducing the risk of HIV transmission. This qualitative study explored the experience of receiving care as well as perceived facilitators and barriers of treatment initiation, retention in ART care, and adherence to treatment., Methods: In-depth interviews were conducted among 28 men who have sex with men (MSM) and female sex workers (FSWs) receiving ART services in Lagos and Benue states. Key informant interviews were also conducted among 16 service providers engaged in counselling, clinical care, and ART treatment for MSM and FSWs. The Social Ecology Model guided the exploration of perceived barriers and facilitators of treatment initiation, retention in ART care and adherence to treatment. Qualitative data analysis was managed using NVIVO 11 software and themes were analysed using thematic analysis., Results: We found that the key barriers to ART adherence were low motivation to comply with medication regimen, work commitments, socioeconomic factors, stigma, negative provider attitude and distance to health facilities. Facilitators of adherence identified include the desire to live a productive life, strong family support and participation in support group programs. Comprehensive adherence counselling, support group programs and an effective follow-up system were factors identified by service providers as key to facilitating adherence., Conclusion: To be effective, ART programs must address the unique challenges key populations face in accessing treatment and achieving optimal adherence regarding establishing a strong support system and follow-up. Community level interventions that support a stigma-free environment are critical to sustaining engagement in care., (© 2024. The Author(s).)

Background: Limited research has explored the effect of Circle of Willis (CoW) anatomy among blunt cerebrovascular injuries (BCVI) on outcomes. It remains unclear if current BCVI screening and scanning practices are sufficient in identification of concomitant COW anomalies and how they affect outcomes., Methods: This retrospective cohort study included adult traumatic BCVIs at 17 level I-IV trauma centers (08/01/2017-07/31/2021). The objectives were to compare screening criteria, scanning practices, and outcomes among those with and without COW anomalies., Results: Of 561 BCVIs, 65% were male and the median age was 48 y/o. 17% (n = 93) had a CoW anomaly. Compared to those with normal CoW anatomy, those with CoW anomalies had significantly higher rates of any strokes (10% vs. 4%, p = 0.04), ICHs (38% vs. 21%, p = 0.001), and clinically significant bleed (CSB) before antithrombotic initiation (14% vs. 3%, p < 0.0001), respectively. Compared to patients with a normal CoW, those with a CoW anomaly also had ischemic strokes more often after antithrombotic interruption (13% vs. 2%, p = 0.02).Patients with CoW anomalies were screened significantly more often because of some other head/neck indication not outlined in BCVI screening criteria than patients with normal CoW anatomy (27% vs. 18%, p = 0.04), respectively. Scans identifying CoW anomalies included both the head and neck significantly more often (53% vs. 29%, p = 0.0001) than scans identifying normal CoW anatomy, respectively., Conclusions: While previous studies suggested universal scanning for BCVI detection, this study found patients with BCVI and CoW anomalies had some other head/neck injury not identified as BCVI scanning criteria significantly more than patients with normal CoW which may suggest that BCVI screening across all patients with a head/neck injury may improve the simultaneous detection of CoW and BCVIs. When screening for BCVI, scans including both the head and neck are superior to a single region in detection of concomitant CoW anomalies. Worsened outcomes (strokes, ICH, and clinically significant bleeding before antithrombotic initiation) were observed for patients with CoW anomalies when compared to those with a normal CoW. Those with a CoW anomaly experienced strokes at a higher rate than patients with normal CoW anatomy specifically when antithrombotic therapy was interrupted. This emphasizes the need for stringent antithrombotic therapy regimens among patients with CoW anomalies and may suggest that patients CoW anomalies would benefit from more varying treatment, highlighting the need to include the CoW anatomy when scanning for BCVI., Level of Evidence: Level III, Prognostic/Epidemiological., (© 2024. The Author(s).)

Background: Childcare needs are an understudied social determinant of health. The effect of childcare needs on access to healthcare must be understood to inform health system interventions and policy reform. This study sought to characterize childcare needs, access to childcare, and prior experience with navigating childcare needs in healthcare settings among women in a safety-net population., Methods: We conducted a cross-sectional study of patient-reported survey data collected in-person between April and October 2019. Surveys were administered in waiting rooms of ambulatory services in a large, urban safety-net health system in Dallas, Texas. Survey respondents were derived from a random convenience sample of women waiting for outpatient appointments. Participants were screened for having children under the age of 13 and/or childcare responsibilities for inclusion in the sample. Outcomes of interest included self-reported delayed or missed care, reasons for delayed or missed care, perceived difficulty in accessing childcare, prior methods for managing childcare during healthcare appointments, and prior experience with childcare centers., Results: Among the 336 respondents (96.7% response rate), 121 (36.0%) reported delaying or missing a mean 3.7 appointments/year. Among women with delayed or missed care, 54.5% reported childcare barriers as the primary reason for deferral of care, greater than transportation (33%) or insurance (25%) barriers. Respondents rated childcare access as more difficult than healthcare access. Delayed or missed care due to childcare was more common among White (68.8%) and Black (55.0%) women compared to Hispanic women (34.3%). Common methods of navigating childcare needs during scheduled appointments included bringing children to appointments (69.1%) and re-scheduling or missing the scheduled appointment (43.0%). 40.6% of patients reported leaving an appointment before completion due to childcare needs., Conclusions: Childcare needs are a leading barrier to healthcare among women accessing care in safety-net settings. Unmet childcare needs result in deferral of care, which may impact health outcomes. Childcare access is perceived as more challenging than healthcare access itself. Health system and policy interventions are needed to address childcare as a social determinant of health., (© 2024. The Author(s).)

Background: Angelman syndrome (AS) is a neurodevelopmental disorder associated with severe global developmental delay. However, the ages at which different developmental skills are achieved in these individuals remain unclear. We seek to determine the probability and the age of acquisition of specific developmental milestones and daily living skills in individuals with AS across the different molecular subtypes, viz. class I deletion, class II deletion, uniparental disomy, imprinting defect, and UBE3A variants., Methods: Caregivers participating in a longitudinal multicenter Angelman Syndrome Natural History Study completed a questionnaire regarding the age at which their children achieved specific developmental milestones and daily living skills. The Cox Proportional Hazard model was applied to analyze differences in the probability of achievement of skills at various ages among five molecular subtypes of AS., Results: Almost all individuals, regardless of molecular subtype, were able to walk with support by five years of age. By age 15, those with a deletion had at least a 50% probability of acquiring 17 out of 30 skills compared to 25 out of 30 skills among those without a deletion. Overall, fine and gross motor skills such as holding and reaching for small objects, sitting, and walking with support were achieved within a fairly narrow range of ages, while toileting, feeding, and hygiene skills tend to have greater variability in the ages at which these skills were achieved. Those without a deletion had a higher probability (25-92%) of achieving daily living skills such as independently toileting and dressing compared to those with a deletion (0-13%). Across all molecular subtypes, there was a low probability of achieving independence in bathing and brushing teeth., Conclusion: Individuals with AS without a deletion are more likely to achieve developmental milestones and daily living skills at an earlier age than those with a deletion. Many individuals with AS are unable to achieve daily living skills necessary for independent self-care., (© 2024. The Author(s).)

Background: Clozapine is an off-label drug used in most countries to prevent suicide in individuals with schizophrenia. However, few studies have reported real-world prescription practices. This study aimed to explore the association between a history of suicidal behavior and clozapine prescribing during eight weeks of hospitalization for individuals with early-stage schizophrenia., Methods: This observational cohort study used routine health data collected from a mental health hospital in Beijing, China. The study included 1057 inpatients who had schizophrenia onset within 3 years. History of suicidal behavior was coded from reviewing medical notes according to the Columbia Suicide Severity Rating Scale. Information on antipsychotic use during hospitalization was extracted from the prescription records. Time to clozapine use was analyzed using Cox regression models adjusted for sociodemographic and clinical covariates., Results: The prevalence rates of self-harm, suicidal behavior, and suicide attempt were 12.3%, 7.5%, and 5.4%, respectively. A history of self-harm history was positively associated with clozapine uses upon admission (4.1% vs. 0.8%, exact p = 0.009). Among those who had not used clozapine and had no clozapine contraindication, A history of suicidal behavior increased the possibility of switch to clozapine within 56 days after admission (Hazard Ratio[95% CI], 6.09[2.08-17.83]) or during hospitalization (4.18[1.62-10.78])., Conclusion: The use of clozapine for early-stage schizophrenia was more frequent among those with suicidal behavior than among those without suicidal behavior in China, although the drug instructions do not label its use for suicide risk., (© 2024. The Author(s).)

Objective: In gout, monosodium urate crystals are taken up by macrophages, triggering the activation of the NLRP3 inflammasome and the maturation of IL-1β. This study aimed to investigate the role of integrin CD11b in inflammasome activation in macrophages stimulated by MSU., Methods: BMDM from WT and CD11b KO mice were stimulated in vitro with MSU crystals. Cellular supernatants were collected to assess the expression of the inflammatory cytokines by enzyme-linked immunosorbent assay and western blot methods. The role of integrin CD11b in MSU-induced gouty arthritis in vivo was investigated by intra-articular injection of MSU crystals. Real-time extracellular acidification rate and oxygen consumption rate of BMDMs were measured by Seahorse Extracellular Flux Analyzer., Results: We demonstrate that CD11b-deficient mice developed exacerbated gouty arthritis with increased recruitment of leukocytes in the joint and higher IL-1β levels in the sera. In macrophages, genetic deletion of CD11b induced a shift of macrophage metabolism from oxidative phosphorylation to glycolysis, thus decreasing the overall generation of intracellular ATP. Upon MSU stimulation, CD11b-deficient macrophages showed an exacerbated secretion of IL-1β. Treating wild-type macrophages with a CD11b agonist, LA1, inhibited MSU-induced release of IL-1β in vitro and attenuated the severity of experimental gouty arthritis. Importantly, LA1, was also effective in human cells as it inhibited MSU-induced release of IL-1β by peripheral blood mononuclear cells from healthy donors., Conclusion: Our data identified the CD11b integrin as a principal cell membrane receptor that modulates NLRP3 inflammasome activation by MSU crystal in macrophages, which could be a potential therapeutic target to treat gouty arthritis in human patients., (© 2024. The Author(s).)

Background: Objective and quantifiable markers are crucial for developing novel therapeutics for mental disorders by 1) stratifying clinically similar patients with different underlying neurobiological deficits and 2) objectively tracking disease trajectory and treatment response. Schizophrenia is often confounded with other psychiatric disorders, especially bipolar disorder, if based on cross-sectional symptoms. Awake and sleep EEG have shown promise in identifying neurophysiological differences as biomarkers for schizophrenia. However, most previous studies, while useful, were conducted in European and American populations, had small sample sizes, and utilized varying analytic methods, limiting comprehensive analyses or generalizability to diverse human populations. Furthermore, the extent to which wake and sleep neurophysiology metrics correlate with each other and with symptom severity or cognitive impairment remains unresolved. Moreover, how these neurophysiological markers compare across psychiatric conditions is not well characterized. The utility of biomarkers in clinical trials and practice would be significantly advanced by well-powered transdiagnostic studies. The Global Research Initiative on the Neurophysiology of Schizophrenia (GRINS) project aims to address these questions through a large, multi-center cohort study involving East Asian populations. To promote transparency and reproducibility, we describe the protocol for the GRINS project., Methods: The research procedure consists of an initial screening interview followed by three subsequent sessions: an introductory interview, an evaluation visit, and an overnight neurophysiological recording session. Data from multiple domains, including demographic and clinical characteristics, behavioral performance (cognitive tasks, motor sequence tasks), and neurophysiological metrics (both awake and sleep electroencephalography), are collected by research groups specialized in each domain., Conclusion: Pilot results from the GRINS project demonstrate the feasibility of this study protocol and highlight the importance of such research, as well as its potential to study a broader range of patients with psychiatric conditions. Through GRINS, we are generating a valuable dataset across multiple domains to identify neurophysiological markers of schizophrenia individually and in combination. By applying this protocol to related mental disorders often confounded with each other, we can gather information that offers insight into the neurophysiological characteristics and underlying mechanisms of these severe conditions, informing objective diagnosis, stratification for clinical research, and ultimately, the development of better-targeted treatment matching in the clinic., (© 2024. The Author(s).)

Background: Although the association between mental disorder and metabolic syndrome as a bidirectional relationship has been demonstrated, there is little knowledge of the cumulative and individual effect of these conditions on peripartum mental health. This study aims to investigate the association between metabolic syndrome conditions (MetS-C) and maternal mental illness in the perinatal period, while exploring time to incident mental disorder diagnosis in postpartum women., Methods: This observational study identified perinatal women continuously enrolled 1 year prior to and 1 year post-delivery using Optum's de-identified Clinformatics® Data Mart Database (CDM) from 2014 to 2019 with MetS-C i.e. obesity, diabetes, high blood pressure, high triglycerides, or low HDL (1-year prior to delivery); perinatal comorbidities (9-months prior to and 4-month postpartum); and mental disorder (1-year prior to and 1-year post-delivery). Additionally, demographics and the number of days until mental disorder diagnosis were evaluated in this cohort. The analysis included descriptive statistics and multivariable logistic regression. MetS-C, perinatal comorbidities, and mental disorder were assessed using the International Classification of Diseases, Ninth, and Tenth Revision diagnosis codes., Results: 372,895 deliveries met inclusion/exclusion criteria. The prevalence of MetS-C was 13.43%. Multivariable logistic regression revealed prenatal prevalence (1.64, CI = 1.59-1.70) and postpartum incident (1.30, CI = 1.25-1.34) diagnosis of mental health disorder were significantly higher in those with at least one MetS-C. Further, the adjusted odds of having postpartum incident mental illness were 1.51 times higher (CI = 1.39-1.66) in those with 2 MetS-C and 2.12 times higher (CI = 1.21-4.01) in those with 3 or more MetS-C. Young women (under the age of 18 years) were more likely to have an incident mental health diagnosis as opposed to other age groups. Lastly, time from hospital discharge to incident mental disorder diagnosis revealed an average of 157 days (SD = 103 days)., Conclusion: The risk of mental disorder (both prenatal and incident) has a significant association with MetS-C. An incremental relationship between incident mental illness diagnosis and the number of MetS-C, a significant association with younger mothers along with a relatively long period of diagnosis mental illness highlights the need for more screening and treatment during pregnancy and postpartum., (© 2024. The Author(s).)

Background: Alzheimer's disease is the most common cause of dementia and is characterized by amyloid-β plaques, tau neurofibrillary tangles, and neuronal loss. Although neuronal loss is a primary hallmark of Alzheimer's disease, it is known that non-neuronal cell populations are ultimately responsible for maintaining brain homeostasis and neuronal health through neuron-glia and glial cell crosstalk. Many signaling pathways have been proposed to be dysregulated in Alzheimer's disease, including WNT, TGFβ, p53, mTOR, NFkB, and Pi3k/Akt signaling. Here, we predict altered cell-cell communication between glia and neurons., Methods: Using public snRNA-sequencing data generated from postmortem human prefrontal cortex, we predicted altered cell-cell communication between glia (astrocytes, microglia, oligodendrocytes, and oligodendrocyte progenitor cells) and neurons (excitatory and inhibitory). We confirmed interactions in a second and third independent orthogonal dataset. We determined cell-type-specificity using Jaccard Similarity Index and investigated the downstream effects of altered interactions in inhibitory neurons through gene expression and transcription factor activity analyses of signaling mediators. Finally, we determined changes in pathway activity in inhibitory neurons., Results: Cell-cell communication between glia and neurons is altered in Alzheimer's disease in a cell-type-specific manner. As expected, ligands are more cell-type-specific than receptors and targets. We identified ligand-receptor pairs in three independent datasets and found involvement of the Alzheimer's disease risk genes APP and APOE across datasets. Most of the signaling mediators of these interactions were not significantly differentially expressed, however, the mediators that are also transcription factors had differential activity between AD and control. Namely, MYC and TP53, which are associated with WNT and p53 signaling, respectively, had decreased TF activity in Alzheimer's disease, along with decreased WNT and p53 pathway activity in inhibitory neurons. Additionally, inhibitory neurons had both increased NFkB signaling pathway activity and increased TF activity of NFIL3, an NFkB signaling-associated transcription factor., Conclusions: Cell-cell communication between glia and neurons in Alzheimer's disease is altered in a cell-type-specific manner involving Alzheimer's disease risk genes. Signaling mediators had altered transcription factor activity suggesting altered glia-neuron interactions may dysregulate signaling pathways including WNT, p53, and NFkB in inhibitory neurons., (© 2024. The Author(s).)

Background: Breastfeeding duration is a critical component of infant and child nutrition, providing immediate and long-term benefits to both children and their mothers. This study uses data from the lot quality assurance sampling (LQAS) survey to examine the prevalence, patterns, and determinants of breastfeeding cessation in Uganda., Methods: This study was a secondary analysis of data collected by the cross-sectional LQAS surveys in 2021 and 2022 covering 77 districts in Uganda. The LQAS survey methodology employs a systematic sampling approach to assess whether predefined quality standards are met within specific subgroups of a population. The study employed spatial analysis, bivariate analysis and logistic regression, both with and without clustering, to explore associations between independent variables and breastfeeding cessation. Unadjusted and adjusted odds ratios with 95% confidence intervals were calculated. Statistical significance was set at 5%., Results: Overall, the study analysed 26,377 records of mothers with children under 24 months old. The mothers' mean age was 27.9 years while that of their children was 11.0 months. While the general breastfeeding cessation rate was 17.7%, cessation was highest (49.7%) among mothers of children 18-23 months. Factors associated with increased odds of breastfeeding cessation included older child's age, older mother's age, using modern family planning, being pregnant and having an unknown pregnancy status. Lower odds of breastfeeding cessation were observed among mothers who; were married, lived in larger households, lived in rural residences, whose children received vitamin A supplementation and among all other regions compared to Kampala., Conclusion: One in five mothers cessed breastfeeding before their child reached 2 years, with a significant increase in cessation odds among mothers of older children. These findings underscore the importance of interventions to promote breastfeeding continuation and adequate nutrition for non-breastfed infants, particularly in regions with high cessation rates., (© 2024. The Author(s).)

Background: Telemedicine use increased with the Covid-19 pandemic. The impact of telemedicine on resource use in pulmonary clinics is unknown., Methods: This retrospective cohort study identified adults with pulmonary clinic visits at the University of Miami Hospital and Clinics (January 2018-December 2021). The primary exposure was telemedicine versus in-person visits. Standard statistics were used to describe the cohort and compare patients stratified by visit type. Multivariable logistic regression models evaluated the association of telemedicine with resource use (primarily, computed tomography [CT] orders placed within 7 days of visit)., Results: 21,744 clinic visits were included: 5,480 (25.2%) telemedicine and 16,264 (74.8%) in-person. In both, the majority were < 65-years-old, female, and identified as Hispanic white. Patients seen with telemedicine had increased odds of having CT scans ordered within 7 days (adjusted odds ratio [aOR] 1.34, [95% confidence interval 1.04-1.74]); and decreased odds of chest x-rays (aOR 0.37 [0.23-0.57]). Telemedicine increased odds of contact of any kind with our healthcare system within 30-days (aOR 1.56 [1.29-1.88]) and 90-days (aOR 1.39 [1.17-1.64]). Specifically, telemedicine visits had decreased odds of emergency department visits and hospitalizations (30 days: aOR 0.54 [0.38-0.76]; 90 days: aOR 0.68 [0.52-0.89]), but increased odds of phone calls and electronic health record inbox messages (30 days: aOR 3.44 [2.73-4.35]; 90 days: aOR 3.58 [2.95-4.35])., Conclusions: Telemedicine was associated with an increased odds of chest CT order with a concomitant decreased odds of chest x-ray order. Increased contact with the healthcare system with telemedicine may represent a larger time burden for outpatient clinicians., (© 2024. The Author(s).)

Background: Globally, the counting of deaths based on gender identity and sexual orientation has been a challenge for health systems. In most cases, non-governmental organizations have dedicated themselves to this work. Despite these efforts in generating information, the scarcity of official data presents significant limitations in policy formulation and actions guided by population needs. Therefore, this manuscript aims to evaluate the accuracy, potential, and limits of probabilistic data relationships to yield information on deaths according to gender identity and sexual orientation in the State of Rio de Janeiro., Methods: This study evaluated the accuracy of the probabilistic record linkage to obtain information on deaths according to gender and sexual orientation. Data from two information systems were used from June 15, 2015 to December 31, 2020. We constructed nine probabilistic data relationship strategies and identified the performance and cutoff points of the best strategy., Results: The best data blocking strategy was established through logical blocks with the first and last names, birthdate, and mother's name in the pairing strategy. With a population base of 80,178 records, 1556 deaths were retrieved. With an area under the curve of 0.979, this strategy presented 93.26% accuracy, 98.46% sensitivity, and 90.04% specificity for the cutoff point ≥ 17.9 of the data relationship score. The adoption of the cutoff point optimized the manual review phase, identifying 2259 (90.04%) of the 2509 false pairs and identifying 1532 (98.46%) of the 1556 true pairs., Conclusion: With the identification of possible strategies for determining probabilistic data relationships, the retrieval of information on mortality according to sexual and gender markers has become feasible. Based on information from the daily routine of health services, the formulation of public policies that consider the LGBTQ + population more closely reflects the reality experienced by these population groups., (© 2024. The Author(s).)

Background: Bovine babesiosis is caused by infection with the protozoal parasite Babesia bovis, which is transmitted by Rhipicephalus (Boophilus) spp. It can cause mortality rates up to 90% in immunologically naive Bos taurus cattle. In south Texas, R. (B.) microplus is known to infest nilgai antelope (Boselaphus tragocamelus); however, their susceptibility to infection with B. bovis and their role in the transmission of the parasite remain unknown. In this study, we challenged nilgai antelope with B. bovis and evaluated their susceptibility to infection., Methods: Nilgai were needle inoculated with ≈10 8 B. bovis-parasitized erythrocytes (merozoites) or a homogenate of B. bovis-infected larval ticks (sporozoite) delivered intravenously. Bos taurus beef calves were inoculated in parallel, as this strain of B. bovis is lethal to cattle. Temperature and hematocrit were monitored daily over the course of each study, and whole blood was collected for molecular [polymerase chain reaction (PCR)] and serological [indirect enzyme-linked immunosorbent assay (ELISA)] diagnostic evaluation. Histological sections of nilgai cerebral tissue were examined for evidence of infection. Recipient bovine calves were sub-inoculated with blood from nilgai challenged with either stage of the parasite, and they were monitored for clinical signs of infection and evaluated by a PCR diagnostic assay. Red blood cells (RBCs) from prechallenged nilgai and B. taurus beef cattle were cultured with an in vitro B. bovis merozoite culture to examine colonization of the RBCs by the parasite., Results: Nilgai did not display clinical signs of infection upon inoculation with either the merozoite or sporozoite stage of B. bovis. All nilgai were PCR-negative for the parasite, and they did not develop antibodies to B. bovis. No evidence of infection was detected in histological sections of nilgai tissues, and in vitro culture analysis indicated that the nilgai RBCs were not colonized by B. bovis merozoites. Cattle subinoculated with blood from challenged nilgai did not display clinical signs of infection, and they were PCR-negative up to 45 days after transfer., Conclusions: Nilgai do not appear to be susceptible to infection with a strain of B. bovis that is lethal to cattle. Tick control on these alternative hosts remains a critical priority, especially given their potential to disseminate ticks over long distances., (© 2024. The Author(s).)

Background: Flight can drastically enhance dispersal capacity and is a key trait defining the potential of exotic insect species to spread and invade new habitats. The phytophagous European spongy moths (ESM, Lymantria dispar dispar) and Asian spongy moths (ASM; a multi-species group represented here by L. d. asiatica and L. d. japonica), are globally invasive species that vary in adult female flight capability-female ASM are typically flight capable, whereas female ESM are typically flightless. Genetic markers of flight capability would supply a powerful tool for flight profiling of these species at any intercepted life stage. To assess the functional complexity of spongy moth flight and to identify potential markers of flight capability, we used multiple genetic approaches aimed at capturing complementary signals of putative flight-relevant genetic divergence between ESM and ASM: reduced representation genome-wide association studies, whole genome sequence comparisons, and developmental transcriptomics. We then judged the candidacy of flight-associated genes through functional analyses aimed at addressing the proximate demands of flight and salient features of the ecological context of spongy moth flight evolution., Results: Candidate gene sets were typically non-overlapping across different genetic approaches, with only nine gene annotations shared between any pair of approaches. We detected an array of flight-relevant functional themes across gene sets that collectively suggest divergence in flight capability between European and Asian spongy moth lineages has coincided with evolutionary differentiation in multiple aspects of flight development, execution, and surrounding life history. Overall, our results indicate that spongy moth flight evolution has shaped or been influenced by a large and functionally broad network of traits., Conclusions: Our study identified a suite of flight-associated genes in spongy moths suited to exploration of the genetic architecture and evolution of flight, or validation for flight profiling purposes. This work illustrates how complementary genetic approaches combined with phenotypically targeted functional analyses can help to characterize genetically complex traits., (© 2024. His Majesty the King in Right of Canada as represented by the Minister of Natural Resources and Julien Prunier, Richard Hamelin, Francois Oliver Hebert, Roger C. Levesque, Ilga Porth. Parts of this work were authored by US Federal Government authors and are not under copyright protection in the US; foreign copyright protection may apply.)