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Wastewater receives per- and polyfluoroalkyl substances (PFAS) from diverse consumer and industrial sources, and discharges are known to be a concern for drinking water quality. The PFAS family includes thousands of potential chemical structures containing organofluorine moieties. Exposures to a few well-studied PFAS, mainly perfluoroalkyl acids (PFAA), have been associated with increased risk of many adverse health outcomes, prompting federal drinking water regulations for six compounds in 2024. Here, we find that the six regulated PFAS (mean = 7 to 8%) and 18 measured PFAA (mean = 11 to 21%) make up only a small fraction of the extractable organofluorine (EOF) in influent and effluent from eight large municipal wastewater treatment facilities. Most of the EOF in influent (75%) and effluent (62%) consists of mono- and polyfluorinated pharmaceuticals. The treatment technology and sizes of the treatment facilities in this study are similar to those serving 70% of the US population. Despite advanced treatment technologies, the maximum EOF removal efficiency among facilities in this work was <25%. Extrapolating our measurements to other large facilities across the United States results in a nationwide EOF discharge estimate of 1.0 to 2.8 million moles F y -1 . Using a national model that simulates connections between wastewater discharges and downstream drinking water intakes, we estimate that the sources of drinking water for up to 23 million Americans could be contaminated above regulatory thresholds by wastewater-derived PFAS alone. These results emphasize the importance of further curbing ongoing PFAS sources and additional evaluations of the fate and toxicity of fluorinated pharmaceuticals., Competing Interests: Competing interests statement:The authors declare no competing interest.

In this study, three beverages formulated with quinoa and chickpea flour blends were fermented using Lactobacillus acidophilus LA-5 to assess the effect of lactic acid fermentation on the degree of hydrolysis of plant-based proteins. Additionally, the impact of quinoa and chickpea blends on the protein content and protein solubility in the beverages was evaluated. Fermentation was completed within 10 h, resulting in a decrease in the pH (<4.3) and an increase in titratable acidity and lactic acid (>0.37 % and > 1.7 g/L), respectively. SDS-PAGE and the O-phthalaldehyde method revealed hydrolysis of quinoa and chickpea proteins. A quinoa-to-chickpea ratio of 50 % exhibited the highest protein content (>2 %), solubility (43.6 %), and hydrolysis (35.9 %) after fermentation, indicating that an increase in chickpea improved these parameters in the prepared PBBs. Overall, fermentation using Lactobacillus acidophilus increased plant protein hydrolysis, and legume addition improved the protein content and the nutritional value of plant-based beverages., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: 22q11.2 deletion syndrome (22qDel) is a copy number variant that is associated with psychosis and other neurodevelopmental disorders. Adolescents who are at clinical high risk for psychosis (CHR) are identified based on the presence of subthreshold psychosis symptoms. Whether common neural substrates underlie these distinct high-risk populations is unknown. We compared functional brain measures in 22qDel and CHR cohorts and mapped the results to biological pathways., Methods: We analyzed 2 large multisite cohorts with resting-state functional magnetic resonance imaging data: 1) a 22qDel cohort (n = 164, 47% female) and typically developing (TD) control participants (n = 134, 56% female); and 2) a cohort of CHR individuals (n = 240, 41% female) and TD control participants (n = 149, 46% female) from the NAPLS-2 (North American Prodrome Longitudinal Study-2). We computed global brain connectivity (GBC), local connectivity (LC), and brain signal variability (BSV) across cortical regions and tested case-control differences for 22qDel and CHR separately. Group difference maps were related to published brain maps using autocorrelation-preserving permutation., Results: BSV, LC, and GBC were significantly disrupted in individuals with 22qDel compared with TD control participants (false discovery rate-corrected q < .05). Spatial maps of BSV and LC differences were highly correlated with each other, unlike GBC. In the CHR group, only LC was significantly altered versus the control group, with a different spatial pattern than the 22qDel group. Group differences mapped onto biological gradients, with 22qDel effects being strongest in regions with high predicted blood flow and metabolism., Conclusions: 22qDel carriers and CHR individuals exhibited different effects on functional magnetic resonance imaging temporal variability and multiscale functional connectivity. In 22qDel carriers, strong and convergent disruptions in BSV and LC that were not seen in CHR individuals suggest distinct functional brain alterations., (Copyright © 2024. Published by Elsevier Inc.)

Background: The enduring and severe depression often suffered by Veterans causes immense suffering and is associated with high rates of suicide and disability. This is the first study to evaluate the efficacy and safety of psilocybin in Veterans with severe treatment-resistant depression (TRD)., Methods: 15 Veterans with severe TRD (major depressive episode failing to respond to ≥5 treatments, or lasting >2 years) received 25 mg of psilocybin. Primary outcome was change in Montgomery-Åsberg Depression Rating scale (MADRS) at 3 weeks posttreatment. Response was defined s ≥ 50 % reduction in MADRS, and remission as ≤10 MADRS score. Psychedelic experience was assessed using the Five-Dimensional Altered States of Consciousness scale (5D-ASC). Safety measures included assessment of suicidality and adverse events. Participants on antidepressants were tapered to avoid drug interactions., Results: Of 15 participants, 60 % met response and 53 % met remission criteria at Week 3. At 12 weeks, 47 % maintained response, and 40 % remission. Co-morbid PTSD did not significantly influence study outcomes. The psychedelic experience reported in 5D-ASC did not correlate with response. Participants judged to need antidepressants were restarted and considered non-responders from that timepoint (n = 4). No unexpected adverse events occurred., Limitations: Limitations include the small sample size, and the uncontrolled and unblinded nature of the study., Conclusions: In this first study on psilocybin for Veterans with severe TRD, a surprising response and remission was seen. Many Veterans had PTSD though no moderating impact of response was observed. The degree of psychedelic experience did not correlate with depression changes. Further study is warranted., Trial Registration: ClinicalTrials.gov Identifier: NCT04433858., Competing Interests: Declaration of competing interest TS reported stock options from Psilotec outside the submitted work. ML served as a paid consultant in therapy training for Compass Pathways during the conduct of the study. MO is a consultant for Neurocrine. SA reported grants and nonfinancial support (supply of drug) from Compass Pathways during the conduct of the study and personal fees from LivaNova, Neuronetics, Genomind, and Sage Therapeutics outside the submitted work. No other disclosures were reported., (Published by Elsevier B.V.)

Chromosomes 5 and 7 are large chromosomes that contain close to 1,000 genes each. Deletions of the long arms or loss of the entire chromosome (monosomy) are common defects in myeloid disorders, particularly MDS and AML. Loss of material from either chromosome 5 or 7 results in haploinsufficiency of multiple genes, with some implicated in leukemogenesis. Abnormalities of one or both occur in up to 15% of MDS and AML cases and co-segregate in half of these. Generally, these chromosomal abnormalities are harbingers of adverse risk in both myeloid disorders. A notable exception is del(5q) in 5q- syndrome, a subtype of MDS. In this review, we describe the pathogenesis and genetic consequences of deletions in chromosomes 5 and 7. Furthermore, we provide an overview of current testing methodologies used in the assessment of these chromosomal defects in hematological malignancies and describe the disease associations and prognostic implications of aberrations in chromosomes 5 and 7 in both MDS and AML.

Background: The COVID-19 pandemic amplified the risk environment for people who inject drugs (PWID), making continued access to harm reduction services imperative. Research has shown that some harm reduction service providers were able to continue to provide services throughout the pandemic. Most of these studies, however, focused on staff perspectives, not those of PWID. Our study examines changes in perceptions of access to harm reduction services (e.g., participant reported difficulty in accessing syringes and naloxone) among PWID participating in a longitudinal study conducted through the University of Illinois-Chicago's Community Outreach Intervention Projects field sites during the COVID-19 pandemic., Methods: A COIVD-19 survey module was administered from March 2020-February 2022 to participants of an ongoing longitudinal study of PWID ages 18-30, who were English-speaking, and were residing in the Chicago Metropolitan Area. Responses to the COVID-19 survey module were analyzed to understand how study participants' self-reported access to harm reduction services changed throughout the pandemic. Baseline responses to the survey were analyzed to compare participant-reported drug use behaviors and perceived access to harm reduction services across COIVD-19 time periods. Mixed effects logistic regression was used to examine difficulty in syringe access as an outcome of COVID-19 time period., Results: Participants had significantly lower odds (AOR = 0.28; 95% CI 0.12-0.65) of reporting difficulty in accessing syringes later in the pandemic. However, the majority of participants reported access to syringes and naloxone remained the same as before the pandemic., Conclusions: The lack of perceived changes in harm reduction access by PWID and the decrease in those reporting difficulty accessing syringes as the pandemic progressed suggests the efficacy of adaptations to harm reduction service provision (e.g., window and mobile service) during the pandemic. Further research is needed to understand how the COVID-19 pandemic may have impacted PWIDs' engagement with harm reduction services., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Kristensen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Percutaneous auricular nerve stimulation (neuromodulation) is an analgesic technique involving the percutaneous implantation of multiple leads at various points on/around the ear followed by the delivery of electric current using an external pulse generator. A device is currently available within the USA cleared to treat symptoms from opioid withdrawal, and multiple reports suggest a possible postoperative analgesic effect. The current randomized, controlled pilot study was undertaken to (1) determine the feasibility and optimize the protocol for a subsequent definitive clinical trial and (2) estimate the treatment effect of auricular neuromodulation on postoperative pain and opioid consumption following total knee arthroplasty., Methods: Within the recovery room following primary, unilateral, total knee arthroplasty, an auricular neuromodulation device (NSS-2 Bridge, Masimo, Irvine, California, USA) was applied using three percutaneous leads and one ground electrode. Participants were randomized to 5 days of either electrical stimulation or sham stimulation in a double-masked fashion. Participants were discharged with the stimulator in situ and removed the disposable devices at home. The dual primary treatment effect outcome measures were the cumulative opioid use (oral oxycodone) and the mean of the "average" daily pain measured with the Numeric Rating Scale for the first 5 postoperative days., Results: During the first five postoperative days, oxycodone consumption in participants given active stimulation (n=15) was a median (IQR) of 4 mg (2-12) vs 13 mg (5-23) in patients given sham (n=15) treatment (p=0.039). During this same period, the average pain intensity in patients given active stimulation was a median (IQR) of 2.5 (1.5-3.3) vs 4.0 (3.6-4.8) in those given sham (p=0.014). Awakenings due to pain over all eight postoperative nights in participants given active stimulation was a median (IQR) of 5 (3-8) vs 11 (4-14) in those given sham (p<0.001). No device-related localized cutaneous irritation, systemic side effects, or other adverse events were identified., Conclusions: Percutaneous auricular neuromodulation reduced pain scores and opioid requirements during the initial week after total knee arthroplasty. Given the ease of application as well as the lack of systemic side effects and reported complications, a definitive clinical trial appears warranted., Trial Registration Number: NCT05521516., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2025. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ Group.)

Background: Maternal obesity is associated with significant racial disparities. People who identify as non-Hispanic Black and Latinx are at the highest risk related adverse short- and long-term health outcomes (eg, hypertension in pregnancy and postpartum weight retention). Remote lifestyle interventions delivered during and after pregnancy hold promise for supporting healthy weight outcomes; however, few are tested in groups of people who self-identify as non-Hispanic Black and Latinx or address the neighborhood-level and psychosocial factors driving maternal health disparities. Implementing remote lifestyle interventions within community-based programs that serve birthing people may optimize trust and engagement, promote scalability and sustainability, and have the broadest public health impact., Objective: The goal of this trial is to test the effectiveness of a culturally adapted remote lifestyle intervention (Healthy for Two-Home Visiting) implemented within home visiting compared to usual home visiting services on postpartum weight retention among pregnant or postpartum individuals, in particular those who identify as non-Hispanic Black and Latinx. Facilitators and barriers to implementation of the intervention within home visiting will be examined., Methods: We describe the rationale and protocol for this hybrid type I effectiveness-implementation randomized controlled trial. In this paper, we highlight the community-engaged approach and trial design features that enable the implementation of the intervention within home visiting and demonstrate its applicability to the target population. Participants will be 360 pregnant individuals with overweight or obesity enrolled between 20 and 33 weeks of gestation and randomized 1:1 to Healthy for Two-Home Visiting or usual home visiting services. The primary outcome is weight retention at 6 months post partum, calculated as 6-month postpartum weight minus earliest pregnancy weight (≤18 wk of gestation). The measures of implementation include intervention feasibility, acceptability, reach, adoption, and fidelity. Throughout the paper, we highlight the community input used to improve intervention effectiveness and study implementation and as a strategy to promote maternal health equity., Results: This study was funded in June 2021, and recruitment began in April 2023. As of November 2024, we enrolled 90 participants. Data collection to assess the intervention's effectiveness is expected to end in June 2026. Implementation evaluation is expected to conclude in December 2026., Conclusions: This hybrid type I effectiveness-implementation randomized controlled trial integrates a culturally adapted remote lifestyle intervention into early home visiting services to examine its effectiveness on postpartum weight retention compared to usual home visiting. We anticipate that the study results will enable an understanding of the drivers of successful implementation within a community-based setting to maximize the future sustainability and dissemination of a strategy for reducing long-term obesity and other maternal health disparities., Trial Registration: Clinicaltrials.gov NCT05619705; https://clinicaltrials.gov/study/NCT05619705., International Registered Report Identifier (irrid): DERR1-10.2196/62847., (©Lindsay M Martin, Christine D McKinney, Lia Escobar Acosta, Janelle W Coughlin, Noelene K Jeffers, Alexandra Solano-Umaña, Kathryn A Carson, Nae-Yuh Wang, Wendy L Bennett, Kelly M Bower. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 07.01.2025.)

Introduction: This scoping review examines the application and evolution of the Social-Ecological Model for Adolescent and Young Adult Readiness for Transition (SMART). SMART provides a framework for assessing transition readiness across pediatric chronic conditions. Evaluating its research and clinical applications identifies insights and gaps across conditions and stakeholders., Method: A systematic search of PubMed, CINAHL, Scopus, OVID, and PsycArticles identified primary research applying SMART in English-language, peer-reviewed literature. Literature was critically appraised using the Mixed Methods Appraisal Tool (MMAT) version 2018., Results: Fifteen studies (2013-2024) met the eligibility criteria. SMART has evolved through revisions and adaptations, demonstrating broad applicability with adolescents, young adults, caregivers, and healthcare providers, and has informed practical applications. Future research is warranted to establish construct measurement, criterion validity, and optimal transition outcomes., Discussion: This review explores SMART's versatility in guiding pediatric-to-adult healthcare transitions and identifying key facilitators and barriers to transition. The recent revision of SMART, integrating health equity, enhances its applicability, yet evaluation across diverse settings is crucial., Competing Interests: Conflicts of Interest None to report., (Copyright © 2024 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.)

Wilms tumors are commonly associated with predisposition syndromes. Many of these syndromes are associated with specific phenotypic features and are discussed in the related article from the AACR Pediatric Cancer Working Group. Guidelines for surveillance in this population were published in 2017, but since then several studies have identified new genes with recurrent pathogenic variants associated with increased risk for Wilms tumor development. In general, variants in these genes are less likely to be associated with other phenotypic features. Recently, members of the AACR Pediatric Cancer Working Group met to update surveillance guidelines for patients with a predisposition to Wilms tumors with a review of recently published evidence and risk estimates. Risk estimates for Wilms tumor for the more recently described genes are discussed here along with suggested surveillance guidelines for these populations. Several other emerging clinical scenarios associated with Wilms tumor predisposition are also discussed, including patients with family histories of Wilms tumor and no identified causative gene, patients with bilateral tumors, and patients with somatic mosaicism for chromosome 11p15.5 alterations. This perspective serves to update pediatric oncologists, geneticists, radiologists, counselors, and other health care professionals on emerging evidence and harmonize updated surveillance recommendations in the North American and Australian context for patients with emerging forms of Wilms tumor predisposition., (©2024 American Association for Cancer Research.)

Pneumonia is the second leading cause of hospital admissions and deaths among children <5 years in Uganda. In 2014, Uganda officially rolled out the introduction of the pneumococcal conjugate vaccine (PCV) into routine immunization schedule. However, little is known about the long-term impact of PCV on pneumonia admissions and deaths. In this study, we described the trends and spatial distribution of pneumonia hospital admissions and mortality among children <5 years in Uganda, 2014-2021. We analysed secondary data on pneumonia admissions and deaths from the District Health Information System version 2 during 2014-2021. The proportion of pneumonia cases admitted and case-fatality rates (CFRs) for children <5 years were calculated for children <5 years presenting at the outpatient department. At national, regional, and district levels, pneumonia mortality rates were calculated per 100,000 children <5 years. The Mann-Kendall Test was used to assess trend significance. We found 667,122 pneumonia admissions and 11,692 (2%) deaths during 2014-2021. The overall proportion of pneumonia cases admitted among children <5 years was 22%. The overall CFR was 0.39%, and the overall pneumonia mortality rate among children <5 years was 19 deaths per 100,000. From 2014 to 2021, there were declines in the proportion of pneumonia cases admitted (31% to 15%; p = 0.051), mortality rates (24/100,000 to 14 per 100,000; p = 0.019), and CFR (0.57% to 0.24%; p = 0.019), concomitant with increasing PCV coverage. Kotido District had a persistently high proportion of pneumonia cases that were admitted (>30%) every year while Kasese District had persistently high mortality rates (68-150 deaths per 100,000 children <5 years). Pneumonia admissions, mortality, and case fatality among children <5 years declined during 2013-2021 in Uganda after the introduction of PCV. However, with these trends it is unlikely that Uganda will meet the 2025 GAPPD targets. There is need to review implementation of existing interventions and identify gaps in order to highlight priority actions to further accelerate declines., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Future self-continuity is the relationship between an individual's perception of their present and future selves and is attracting intense interest from researchers in psychology and health. This study aimed to psychometrically evaluate the Future Self-Continuity Questionnaire (FSCQ), a tool designed to measure an individual's future self-continuity, in New Zealand's unique sociocultural context. In Phase 1 we tested the reliability (internal consistency) of the 10 item FSCQ and its three subscales and attempted to replicate the three-factor structure reported previously. In Phase 2 we examined the FSCQ's correlations with established measures like the Future Self-Continuity Scale (FSCS), Consideration of Future Consequences (CFC-14) Scale, Multidimensional Temporal Self-Continuity Scale (MTSCS), and Beck Hopelessness Scale (BHS). Results from the first phase confirmed the FSCQ's reliability and construct validity, with strong internal consistency (α ranged from .77 to .87) and a good factorial structure (GFI=.97, RMSEA=.04). In the second phase, the FSCQ demonstrated positive correlations with the FSCS, CFC-14, and MTSCS, and negative correlations with the BHS. These findings suggest that the FSCQ reliably measures FSC, has a robust replicable three-factor structure and is consistent with other relevant psychological constructs. This study demonstrates the applicability of the FSCQ outside the United States for the first time.

Child maltreatment is a major public and global health issue with well-documented intergenerational patterns. Social-emotional development, which is detrimentally impacted by child maltreatment, has been associated with parenting behaviors and implicated as a mechanism of intergenerational transmission of child maltreatment. This scoping review sought to synthesize information on the social-emotional skills that contribute to or protect against intergenerational maltreatment. Following the JBI Manual for Evidence Synthesis systematic scoping review methodology, 23 studies were identified as having met all inclusion criteria. Eligible studies were empirical, primary, peer-reviewed and published work written in English. Included studies contained a parental history of maltreatment, maltreatment or risk thereof to the child, and at least one independent parental social-emotional factor. Studies were organized, and findings were conceptually mapped according to Collaborative for Academic, Social, and Emotional Learning (CASEL) social-emotional competency domains. Key findings included determining self-management as the most well-studied CASEL competency area, whereas there was a paucity of research on relationship skills and responsible decision-making. Studies focused almost exclusively on assessing risk. The most well-documented risk factors for intergenerational maltreatment included parental emotion dysregulation, low self-control, aggression, and dissociation. Measurement and consideration of the developmental timing of maltreatment was identified as a critical oversight in the literature. Future work should explore developmentally specific models and elucidate more comprehensive profiles of social-emotional risk and resilience as a means of developing more effective prevention strategies., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Intestinal transplantation (ITx) has become an accepted option for children with serious complications from intestinal failure and parenteral nutrition (PN) dependence. We aimed to assess long-term growth and nutritional outcomes in these patients. We also assessed factors influencing nutritional status and ability to wean off tube feedings (TFs) after ITx., Methods: We looked retrospectively into post-ITx growth parameters, nutrition treatment, and micronutrient status for children who survived for 5 or more years after ITx. One hundred thirty-three children between 1993 and 2014 were involved. Descriptive data and growth parameters were collected over 15 years after ITx. We also analyzed influencing factors, including the presence of permanent stoma, prolonged use of steroids, partial gastrectomy at the time of ITx, developmental delay, concurrent visceral transplant, and graft rejection episodes., Results: There was an increase in the height z-scores over the 15-year period post-ITx (p < 0.001). There was a downward trend in body mass index (BMI) z-scores over the 15-year post-ITx period. Isolated intestinal transplant patients showed a better height z-score compared to multivisceral transplant (p = 0.04). The height and BMI z-scores for patients on steroids were not significantly different from the z-scores for steroid-free patients (p = 0.72, 0.99, respectively). There was no significant change in height and BMI z-scores based on prednisolone dose: ≤0.2 mg/kg (p = 0.76); >0.2 mg/kg (p = 0.52). Patients were more likely to require supplemental TF up to 15 years post-ITx when they had partial gastrectomy (p < 0.001), permanent ostomy (p = 0.009), or developmental delay (p < 0.001)., Conclusions: There was improved long-term linear growth post-ITx. Developmental delay, partial gastrectomy, and a permanent ostomy are likely to delay TF wean post-ITx., (© 2025 The Author(s). Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: Intracerebral hemorrhage (ICH) is stroke caused by non-traumatic bleeding into the brain., Aim: This factsheet provides summary statistics for ICH from the 2021 Global of Burden of Diseases Study., Methods: Data were downloaded from the GBD results platform using "intracerebral hemorrhage" as a Level 4 cause of death or injury, extracting key metrics (number, percent, rate) for measures (incidence, disabilty adjusted life years [DALYs], deaths) described in this factsheet., Results: Globally, stroke was the third leading cause of death in 2021, and ICH accounted for 28.8% of incident strokes. There were estimated to be 7,252,678 deaths due to stroke in 2021 of which ICH accounted for 3,308,367 (45.6%). When considering the burden of ICH in terms of DALYs, ICH accounts for nearly half of the burden of stroke at 49.5%, compared to 43.8% caused by ischemic stroke. ICH must therefore be considered on an equal footing with ischemic stroke, so that efforts can be made to reduce its burden through public health, research, and healthcare provision. Although the overall age-standardized incidence of ICH has been decreasing since 1990, the rate of reduction has been much slower in regions with lower socio-demographic index (SDI). Most of the burden of ICH lies in areas with lower SDI, with 94.2% of DALYs lost to ICH outside areas of high SDI. Geographically, the majority of DALYs due to ICH occur in Southeast Asia, East Asia, and Oceania, with 53.3% of global DALYs lost in these regions alone. The risk factors for ICH are dominated by high systolic blood pressure, which accounts for at least 50% of the burden of ICH, regardless of SDI. Areas with middle or high-middle SDI have a greater proportion of the burden of ICH accounted for by ambient particulate pollution, smoking, and diets high in sodium, whereas household air pollution from solid fuels accounts for much more of the risk of ICH in low SDI regions., Conclusion: This World Stroke Organization (WSO) Global ICH Fact Sheet 2025 provides the most updated information on ICH that can be used to support communication with all internal and external stakeholders, inform healthcare policy, and raise public awareness. All statistics have been reviewed and approved for use by the WSO Executive Committee., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The sharp increase in the cost of living in the UK over the past few years has affected all populations, including higher education students. Many higher education students, including nursing students, are experiencing financial difficulties and concerns, which adversely affect their mental health and can cause them to consider leaving their course. This article reports the findings of an online survey undertaken in one university in Glasgow, Scotland, that aimed to explore the effects of financial stress on second and third-year nursing students. Most respondents had experienced financial worries since starting their preregistration nursing degree programme; many were concerned about the cost of living, and financial worries adversely affected their academic performance and clinical placements. The authors suggest there is a need for a collaborative partnership between universities and practice placement areas to adopt a student-centred approach to identifying solutions to nursing students' financial concerns as well as a review of the available funding for this cohort., Competing Interests: None declared, (© 2025 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.)

Background: Improving the infrastructure for drug overdose surveillance is critical for identifying new threats and responding to emerging trends. We aimed to develop a prototype tool using the principles of natural language processing that can extract information from the death records of drug overdose victims., Methods: Data were obtained from the Violent Death Reporting System on drug overdose deaths. Narratives were manually labelled for 12 attributes of interest, totalling 82 labels about the circumstances of the overdose. Narratives were passed through the 'Excel Extractor' to identify and extract a target phrase and subsequently map the extracted phrase to predetermined code values. The output from the Excel Extractor was compared with manually labelled data to determine accuracy. Performance was compared against multiple machine learning models., Results: The Excel Extractor performed well across the attributes of interest, achieving an F1 Score over 0.8 on nine of the 12 attributes. The Excel Extractor was the highest performing model on seven of the 12 attributes. The Excel Extractor achieved an F1 Score of 0.8 or higher on 46 of 82 (56%) of the labels, and a score of 0.9 or higher on nearly one-third (25 out of 82) of the labels., Conclusion: This work demonstrates it is feasible to develop a spreadsheet-formula-based natural language processing tool to accurately extract information about drug overdose deaths from narratives; for most attributes, a rule-based search performs well or better than deep learning. The Excel Extractor has the potential to streamline data abstraction for epidemiologists gathering data about drug overdose deaths., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Importance: Doxycycline postexposure prophylaxis (doxyPEP) has been shown to decrease the incidence of bacterial sexually transmitted infections (STIs) among people assigned male sex at birth in clinical trials, but data from clinical practice are limited., Objective: To describe early uptake of doxyPEP and evaluate changes in STI incidence following doxyPEP initiation., Design, Setting, and Participants: This retrospective cohort study of adults (aged ≥18 years) dispensed HIV preexposure prophylaxis (PrEP) at Kaiser Permanente Northern California during November 1, 2022, to December 31, 2023, examined electronic health record data to compare HIV PrEP users dispensed and not dispensed doxyPEP and rates of bacterial STIs before and after starting doxyPEP. Individuals were followed up from their first recorded STI test on or after November 1, 2020, until December 31, 2023, or discontinuation of health plan membership., Exposure: Pharmacy dispensing data were used to define doxyPEP recipients., Main Outcomes and Measures: Demographic and clinical characteristics were compared between individuals dispensed and not dispensed doxyPEP. Primary outcomes were incident chlamydia, gonorrhea, or infectious syphilis measured as quarterly STI positivity (proportion of individuals testing positive at least once per quarter). Among doxyPEP recipients, rate ratios (RRs) compared mean quarterly STI positivity from 24 months before to 12 months after starting doxyPEP. In an exploratory analysis, STI trends were evaluated for the full cohort, stratified by receipt of doxyPEP., Results: Among 11 551 HIV PrEP users (mean [SD] age, 39.9 [12.1] years; 95.1% male), 2253 (19.5%) were dispensed doxyPEP, of whom 2228 (98.9%) were male and 1096 (48.6%) had an STI in the year before starting doxyPEP. Compared with individuals not dispensed doxyPEP, doxyPEP recipients were older (mean [SD] age, 40.4 [10.8] vs 39.8 [12.4] years; P = .04) and had used HIV PrEP longer (mean [SD], 4.2 [2.8] vs 3.4 [2.6] years; P < .001), and a higher proportion were commercially insured (2091 [92.8%] vs 8270 [88.9%]; P < .001). Among doxyPEP recipients, quarterly chlamydia positivity decreased from 9.6% (95% CI, 9.0%-10.3%) before starting doxyPEP to 2.0% (95% CI, 1.5%-2.6%) after starting doxyPEP (RR, 0.21; 95% CI, 0.16-0.27; P < .001), with significant declines for each anatomic site of infection. Quarterly gonorrhea positivity decreased from 10.2% (95% CI, 9.6%-10.9%) before starting doxyPEP to 9.0% (95% CI, 8.0%-10.1%) after starting doxyPEP (RR, 0.88; 95% CI, 0.77-1.00; P = .048); site-specific declines were significant for rectal (RR, 0.81; 95% CI, 0.67-0.97; P = .02) and urethral (RR, 0.56; 95% CI, 0.40-0.79; P = .001) gonorrhea, but not pharyngeal gonorrhea. Quarterly syphilis positivity decreased from 1.7% (95% CI, 1.4%-1.9%) before starting doxyPEP to 0.3% (95% CI, 0.2%-0.6%) after starting doxyPEP (RR, 0.20; 95% CI, 0.11-0.37; P < .001). Positivity for STIs remained stable in individuals not dispensed doxyPEP., Conclusions and Relevance: This study found that receipt of doxyPEP was associated with substantial declines in chlamydia and syphilis incidence and modest declines in urethral and rectal gonorrhea incidence among individuals using HIV PrEP. These findings suggest that doxyPEP may offer substantial benefits for reducing population-level STI transmission with broader implementation.

Haematological malignancies affect 12·5 in 100 000 pregnancies. Over the past two decades, the number of haematological malignancies in pregnancy has substantially increased. Life-threatening haematological malignancies in pregnancy, such as acute leukaemia and aggressive lymphomas, pose a unique therapeutic challenge: clinicians must consider both maternal and fetal wellbeing, aiming to deliver optimal curative therapy for the patient and a successful pregnancy outcome. A multidisciplinary approach to disease management is paramount, and there are currently no clinical practice guidelines available. An Australasian working group, including representatives from haematology, obstetric medicine, clinical teratology, radiology, nuclear medicine, maternal-fetal medicine, and a patient representative, was established to develop this position statement, which is based on a combination of current evidence and expert consensus. We provide recommendations for diagnosis and staging, imaging safety in pregnancy, therapy in pregnancy incorporating a multidisciplinary approach, supportive care, oncofertility, and pregnancy and birth management. This Viewpoint was reviewed and endorsed by the councils of the Society of Obstetric Medicine of Australia and New Zealand, the Haematology Society of Australia and New Zealand, and the Haematology in Obstetric and Women's Health Collaborative., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Introduction: Unmet oral health needs remain a significant issue among immigrant adolescents, often exacerbated by experiences of racial discrimination. This study aimed to examine the associations between perceived discrimination and oral health behaviours in adolescents with immigrant backgrounds and explore the potential moderating role of resilience on this association., Methods: Ethical approval for this cross-sectional study was obtained from the University of Alberta Research Ethics Board. Participants were 12 to 18-year-old adolescents from immigrant backgrounds. Participants were recruited through nine community organizations using a snowball sampling technique. After obtaining active parental consent and assent from the adolescent, the participants completed a questionnaire covering demographics, oral health behaviours, and perceived racial discrimination and resilience. Perceived racial discrimination and resilience were measured using validated scales. Descriptive statistics summarized variables. Logistic regression assessed associations, controlling for confounding factors. Resilience's moderating impact was analyzed via the interaction model of regression analysis., Results: In this cross-sectional study of 316 participants, average age of 15.3 (SD = 1.9) years, and a median age of 15 years (Inter Quartile Range-12-18), 76% reported discrimination experiences. Adjusted analysis showed that an increase of one unit in the total discrimination distress score was associated with 51% less likelihood of categorizing self-rated oral health as good (OR = 0.49, 95% CI: 0.29-0.81). The odds of brushing teeth more than twice a day, as opposed to once a day, decreased by 58% with one unit increase in the total discrimination distress score (OR = 0.42, 95% CI: 0.25-0.71). The odds of visiting the dentist for an urgent procedure instead of a regular check-up were 2.3 times higher with a unit increase in the total discrimination distress score (OR = 2.3: 95% CI:1.3-4.0) Resilience did not moderate the observed association., Conclusion: Perceived racial discrimination was associated with the pattern for dental attendance, tooth brushing frequency, and self-rated oral health. Resilience did not moderate the observed association., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Saluja et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Ebola virus (EBOV) causes severe human disease. During late infection, EBOV virions are on the skin's surface; however, the permissive skin cell types and the route of virus translocation to the epidermal surface are unknown. We describe a human skin explant model and demonstrate that EBOV infection of human skin via basal media increases in a time-dependent and dose-dependent manner. In the dermis, cells of myeloid, endothelial, and fibroblast origin were EBOV antigen-positive whereas keratinocytes harbored virus in the epidermis. Infectious virus was detected on the apical epidermal surface within 3 days, indicating that virus propagates and traffics through the explants. Purified human fibroblasts and keratinocytes supported EBOV infection ex vivo and both cell types required the phosphatidylserine receptor, AXL, and the endosomal protein, NPC1, for virus entry. This platform identified susceptible cell types and demonstrated dynamic trafficking of EBOV virions. These findings may explain person-to-person transmission via skin contact.

Background: Newborn screening is a public health system designed to identify infants at risk for conditions early in life to facilitate timely intervention and treatment to prevent or mitigate adverse health outcomes. Newborn screening programs use tandem mass spectrometry as a platform to detect several treatable inborn errors of metabolism, and the T-cell receptor excision circle assay to detect some inborn errors of the immune system. Recent advancements in DNA sequencing have decreased the cost of sequencing and allow us to consider DNA sequencing as an additional platform to complement other newborn screening methods., Content: This review provides an overview of DNA-based newborn screening, including its applications, opportunities, challenges, and future directions. We discuss the potential benefits of expanded DNA sequencing in newborn screening, such as expanding conditions screened and improved specificity and sensitivity of currently screened conditions. Additionally, we examine the ethical, legal, and social implications of implementing genomic sequencing in newborn screening programs, including issues related to consent, privacy, equity, data interpretation, scalability, and psychosocial impact on families. Additionally, we explore emerging strategies for addressing current limitations and advancing the field of newborn screening., Summary: DNA sequencing in newborn screening has the potential to improve the diagnosis and management of rare diseases but also presents significant challenges that need to be addressed before implementation at the population level., (© Association for Diagnostics & Laboratory Medicine 2025. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose: School-based teams are called to be collaborative in order to appropriately and effectively serve students. Speech-language pathologists play crucial roles on school-based teams. This systematic review sought to synthesize existing empirical evidence on collaborative perceptions and experiences in research that included school-based speech-language pathologists (SLPs)., Method: A systematic literature review was conducted, which included Boolean search methods of the Science Citation Index Expanded, Social Sciences Citation Index, Education Resources Information Center, Academic Search Complete, Education Research Complete, and PubMed databases. Through an abstract, text screening, and progeny search process, 26 articles met the study's inclusion criteria. Relevant data were extracted from each article, analyzed, synthesized, and organized into themes to answer the research questions., Results: The main findings from the systematic review were organized into (a) study design and participants; (b) purpose, definitions, and collaborative activities; (c) perceptions of collaboration; (d) engagement in collaboration; (e) facilitators and barriers; (f) collaboration and telepractice; and (g) differing findings based on demographic factors., Conclusions: Underscoring the complexity of school-based collaboration, researchers have utilized varied designs and frameworks to explore collaborative perceptions and experiences in research including school-based SLPs. While SLPs generally view school-based collaboration as valuable, engagement in collaboration is not as clear-cut. The number of facilitators and barriers described, variability in frameworks and definitions, and limited disaggregation across demographic factors underlie the need for continued research and have implications for policy and practice.

Objective: To assess the influence of neighborhood socioeconomic deprivation on the effectiveness of an intensive lifestyle intervention (ILI) in the Look AHEAD trial., Research Design and Methods: Look AHEAD randomized adults with overweight/obesity and type 2 diabetes to ILI for weight loss, or Diabetes Support and Education (DSE). We linked participant data from four study sites to the 2000 United States Census to generate a neighborhood socioeconomic deprivation score. We analyzed the effect of neighborhood deprivation in tertiles on various clinical outcomes including weight and HbA1c changes over 4 years using a mixed-effects linear model with random intercept and an interaction term between deprivation tertile and study arm over 4 years., Results: Among 1213 participants at baseline, the mean age was 60 years, 41% were male, and 65% identified as White, 26% as Black, and 4% as Hispanic. Most participants had a college degree (84%) and reported an annual income over $40,000 (75%). The deprivation score ranged from -12.04 to -2.61 in the most deprived tertile and 2.01 to 18.69 in the least deprived tertile (the lower the score, the higher the deprivation). There were no statistically significant treatment differences by deprivation score in weight or HbA1c changes over the 4-year period., Conclusions: In this clinical trial population, an intensive lifestyle intervention was equally effective across levels of neighborhood socioeconomic deprivation. However, these findings may not extend to individuals with the lowest income and educational attainment who are not typically represented in clinical trials and for whom more research is needed., Competing Interests: Declarations:. Conflict of Interest: The authors declare that they do not have a conflict of interest., (© 2024. The Author(s).)

In a given year, 1 in 6 youth will experience a mental health disorder. 1 Prevalence data reveal that anxiety (9.4%), attention-deficit/hyperactivity disorder (9.8%), and behavior problems (8.9%) are the most common mental disorders in youth. 2 With the coronavirus disease (COVID-19) pandemic, psychiatric needs skyrocketed because of factors such as isolation from social networks, disruption in routines, reduction in physical activities, and increased social media use. 3 As a result, symptoms of depression and anxiety doubled and suicide attempts rose, which illuminated the mental health crisis among children and adolescents. 4,5 More concerning, this trend has had a disproportionate impact on racially minoritized communities, who also had to grapple with significant compounding stressors related to inequitable health care access, police brutality, xenophobia, and more. 6 For instance, exposure to personal and indirect racial discrimination through channels such as social media resulted in elevated worry and stress among Black and Asian American youth. 6 Furthermore, across different racial groups, the percentage of youth injured from a suicide attempt only increased for Black youth from 2019 to 2021. 7 Despite these needs, mental health service use rates among racially minoritized youth remain low compared to those of their White counterparts. Moreover, once and if care is provided, racially minoritized youth report poorer quality services, contributing to premature termination and unmet mental health needs. 8 Thus, strategies that promote racially minoritized youths' engagement in services are warranted to address mental health inequities., (Copyright © 2024 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objectives: The aims of the study are to characterize children with mental and behavioral health conditions (MBH) transported by emergency medical services (EMS) and examine differences in patient, emergency department (ED), and EMS transport characteristics based on restraint interventions during EMS transport., Methods: This is a retrospective cohort study of EMS patients with MBH crises, aged 5-18, transported to 2 pediatric EDs over 9 years. Demographic and ED data were collected electronically; EMS data were extracted manually from prehospital care records. Field interventions studied included pharmacologic and mechanical restraints by EMS clinicians. Univariate analysis compared variables between patients who received EMS restraints and those who did not and multivariable logistic regression identified patient factors independently associated with EMS restraint use., Results: Among 10,264 patients transported by EMS for MBH crises, 1400 encounters were randomly selected, with 768 records available. EMS restraint interventions were used in 73 (9.5%) patients: 5 (0.7%) received only pharmacologic restraints, 58 (7.6%) received only physical restraints, and 10 (1.3%) received both. Those who received EMS restraints were more likely to be younger (35.6% vs 19.6%, P = 0.001), male (71.2% vs 44.6%, P < 0.0001), and had longer scene times (13 vs 9 min). Restraint use was more common when patients were picked up from schools (30.1% vs 14.8%, P = 0.007). EMS-restrained patients were also more likely to receive physical (12.3% vs 2.3%, P < 0.0001), mechanical (15.1% vs 1.0%, P < 0.0001), or pharmacologic (24.7% vs 3.9%, P < 0.0001) restraints in the ED. Predictors of EMS restraint use were male sex (odds ratio, 3.00; 95% confidence interval, 1.74-5.17) and being picked up from schools (odds ratio, 2.08; 95% confidence interval, 1.13-3.81), whereas age group, race, and insurance type were not independent predictors., Conclusions: Nearly 1 in 10 pediatric patients experiencing mental health crises and transported by EMS required restraint interventions in the field. Male patients, younger aged children, and those picked up from school represent a distinct and vulnerable population that could benefit from specialized prehospital care to manage agitation., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Academic clinical nurse educators are valued for their current clinical expertise; however, they often have little training in pedagogy. Current research has focused on strategies to improve orientation, support, confidence, and retention. The purpose of this paper is to analyze and evaluate transition theory and basic needs theory as they relate to the phenomenon of becoming a clinical instructor. After analysis and review, basic needs theory was determined to be a useful, parsimonious theory to examine the phenomenon of becoming a clinical instructor and may allow for developing interventions to increase the intrinsic motivation of academic clinical nurse educators., Competing Interests: Declaration of Conflicting InterestsThe author declared no potential conflicts of interest with respect to the authorship and/or publication of this review.

Background: Nivolumab obtained approval in advanced melanoma (AM) with weight-adjusted dose (WAD) administration (3 mg/kg/2 weeks). In 2018, the dosage regimen was changed to flat dose (FD) administration (240 mg/2 weeks or 480 mg/4 weeks) based on a modeling study, without clinical data., Methods: AM patients have been prospectively included in the French national multicenter MelBase database since 2013. First-line patients treated with nivolumab monotherapy were included in the WAD or FD groups of this study. The primary end point was the incidence of grade ≥3 immune-related adverse events (irAEs). Secondary end points were incidence of any grade irAEs, and overall survival (OS) and progression-free survival (PFS). Inverse probability of treatment weighting was used to balance groups on their baseline characteristics., Results: Between 2015 and 2022, 348 patients were included: 160 in the WAD and 188 in the FD groups. In the FD group, 45% and 27% of patients weighed <75 kg and >85 kg, respectively. Grade ≥3 and any grade irAEs rates were 13.1% versus 11.7% (p = .8) and 63.1% versus 67.0% (p = .5) in the WAD and FD groups, respectively. After weighting, median PFS was 3.1 and 3.7 months (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.65-1.07), and median OS was 24.8 and 37.0 months (HR, 0.74; 95% CI, 0.54-1.01) in the WAD and FD groups, respectively., Conclusions: There was no difference in the incidence of severe irAEs and in median PFS between AM patients treated by WAD or FD nivolumab. The median OS between patient groups did not reach statistical significance., (© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Anthropogenically driven environmental change has imposed substantial threats on biodiversity, including the emergence of infectious diseases that have resulted in declines of wildlife globally. In response to pathogen invasion, maintaining diversity within host populations across heterogenous environments is essential to facilitating species persistence. White-nose syndrome is an emerging fungal pathogen that has caused mass mortalities of hibernating bats across North America. However, in the northeast, peripheral island populations of the endangered northern myotis ( Myotis septentrionalis ) appear to be persisting despite infection while mainland populations in the core of the species range have experienced sharp declines. Thus, this study investigated host and environmental factors that may contribute to divergent population responses. We compared patterns of pathogen exposure and infection intensity between populations and documented the environmental conditions and host activity patterns that may promote survival despite disease invasion. For island populations, we found lower prevalence and less severe infections, possibly due to a shorter hibernation duration compared to the mainland, which may reduce the time for disease progression. The coastal region of the northern myotis range may serve as habitat refugia that enables this species to persist despite pathogen exposure; however, conservation efforts could be critical to supporting species survival in the long term.

Introduction: Child marriage is practiced widely in West and Central Africa with established links to several negative outcomes, particularly for girls. Although some reviews on predictors of the practice of child marriage exist, to date no review has focused on the costs and potential benefits to girls who have experienced child marriage., Method: We conducted a scoping review of PubMed, African Index Medicus, Embase, PsycINFO, Web of Science, and Global Health and in the grey literature for studies on child marriage and adjustment up to October 2023. Studies were included if they assessed marriages where the female was younger than 18 at the time of marriage, were conducted in Central and Western African countries, explored positive and/or negative indicators of well-being and mental health in the context of child marriage, were written in English, were published in a peer-reviewed journal, or was a published thesis or dissertation, grey literature, or technical report, were conducted between 2014 and 2023, and presented qualitative, quantitative, or mixed-method data., Results: Based on the inclusion criteria, we included nine qualitative and four quantitative studies. Using the lens of Self-Determination Theory, we found that overall child marriage compromised needs for autonomy, competence, and relatedness. Further, child marriage was linked to negative mental health outcomes. However, for some girls, child marriage was associated with some benefits including social recognition and elevated status in society., Conclusion: Future research on adjustment within the context of child marriage should focus on all aspects of well-being as well as the processes associated with adjustment for girls., (© 2024 Foundation for Professionals in Services to Adolescents.)

Abstract: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is the most common type of autoimmune encephalitis. The initial presentation can vary from subtle mental status changes to more severe symptoms such as seizures, coma, or death. This case report outlines the interdisciplinary and collaborative approach to diagnosing and treating a patient with anti-NMDAR autoimmune encephalitis., (Copyright © 2025 American Academy of Physician Associates.)

Background: Adolescents and young adults with cancer (AYAs, ages 15-39 at the time of diagnosis) experience significant adverse health and psychosocial outcomes. AYAs live with emotional distress and health care demands that exceed those of their healthy peers but can have difficulty accessing care. Digitally delivered interventions are an attractive option for AYA survivors, a population that routinely utilizes online resources when seeking health information and support., Aim: By improving access to survivorship resources and support and strengthening health literacy and self-management skills, the INteractive Survivorship Program to Improve Health care REsources [INSPIRE] is designed to improve adherence to AYA health care guidelines and reduce cancer-related distress. We describe the protocol for a two-arm randomized controlled trial (RCT) testing the AYA-adapted INSPIRE program., Methods/design: The intervention includes an interactive mobile app, study website, and social media platforms, adding telehealth for those with continued distress, lower survivorship health care literacy, or poor engagement with the digital program at 6 weeks. Participants are randomized to INSPIRE or an active control. In the active control arm, survivors receive access to a study website with links to existing AYA survivor resources followed by delayed access to the INSPIRE program. Participants are not blinded; study staff not providing telehealth are blinded. The primary outcomes are cancer-related distress and health care adherence specific to second cancer and cardiometabolic screenings., Discussion: If effective, the program is positioned for accelerated implementation to improve care for AYA survivors by using a scalable informatics-based administration and largely digital intervention program., Competing Interests: Declaration of competing interest The authors declare no relevant conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Objectives: Limited research has examined how discrimination in young adulthood relates to substance use. We examined how multiple and specific types (e.g., race-based) of experiences of unfair treatment are related to problematic alcohol and cannabis use., Methods: We analyzed cross-sectional data from a diverse cohort of young adults (mean age 24.7) predominantly residing in southern California (n = 2303) to examine associations of multiple (count) and specific experiences (race-, sexual orientation-, gender-based) of perceived everyday discrimination with self-reported alcohol and cannabis use outcomes (consequences, use disorders, and solitary use). We also tested interactions between the three specific discrimination experiences and sociodemographic characteristics (e.g., race-based discrimination × race/ethnicity)., Results: In this diverse sample (e.g., 47% Latinx/o and 22% Asian; 22% sexual/gender diverse; 56% female) of young adults, about 46% reported up to four different discrimination experiences and 27% reported race-, 26% gender-, and 5% sexual orientation-based discrimination. Race- and gender-based discrimination and experiencing more types of discrimination were associated with worse cannabis use outcomes. Race-based discrimination was associated with fewer alcohol consequences and lower Alcohol Use Disorders Identification Test (AUDIT) scores. Associations with sexual orientation-based discrimination and the interactions were not significant., Discussion and Conclusions: Findings build on limited research on associations of discrimination with cannabis use in young adults. More work is needed to understand the mechanisms by which discrimination influences drinking behaviors., Scientific Significance: This study advances the field by examining the unique contributions of specific and multiple types of discrimination experiences in young adulthood, a critical developmental period in which substance use peaks., (© 2024 The American Academy of Addiction Psychiatry (AAAP).)

The forces generated by action potentials in muscle cells shuttle blood, food and waste products throughout the luminal structures of the body. Although non-invasive electrophysiological techniques exist 1-3 , most mechanosensors cannot access luminal structures non-invasively 4-6 . Here we introduce non-toxic ingestible mechanosensors to enable the quantitative study of luminal forces and apply them to study feeding in living Caenorhabditis elegans roundworms. These optical 'microgauges' comprise upconverting NaY 0.8 Yb 0.18 Er 0.02 F 4 @NaYF 4 nanoparticles embedded in polystyrene microspheres. Combining optical microscopy and atomic force microscopy to study microgauges in vitro, we show that force evokes a linear and hysteresis-free change in the ratio of emitted red to green light. With fluorescence imaging and non-invasive electrophysiology, we show that adult C. elegans generate bite forces during feeding on the order of 10 µN and that the temporal pattern of force generation is aligned with muscle activity in the feeding organ. Moreover, the bite force we measure corresponds to Hertzian contact stresses in the pressure range used to lyse the bacterial food of the worm 7,8 . Microgauges have the potential to enable quantitative studies that investigate how neuromuscular stresses are affected by ageing, genetic mutations and drug treatments in this organ and other luminal organs., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature Limited.)

Islatravir is a nucleoside reverse transcriptase translocation inhibitor in development for the treatment of HIV-1. People living with HIV-1 receiving methadone maintenance therapy may benefit from islatravir. This study was designed to evaluate single-dose islatravir on steady-state methadone pharmacokinetics. A nonrandomized, open-label study (NCT04568603) was conducted and included adult participants receiving methadone therapy. Participants received their standard methadone therapy and a single oral dose of islatravir 60 mg concomitantly. Blood samples were collected to determine methadone and islatravir pharmacokinetics. Fourteen participants aged 26-63 years were enrolled; 13 completed the study. The geometric mean ratios for methadone area under the concentration-time curve from time 0 to 24 hours (AUC 0-24 ), maximum plasma concentration (C max ), and concentration at 24 hours (C 24 ) were 1.03, 1.01, and 1.07, respectively. Similar effects were seen for the R- and S-enantiomer of methadone (R-methadone: AUC 0-24 , 1.03; C max , 1.02; and C 24 , 1.06; S-methadone: AUC 0-24 , 1.03; C max , 1.01; and C 24 , 1.08). For islatravir, based on a comparison with historical data, the geometric mean ratios for AUC 0-inf and C max were 1.18 and 0.86, respectively. Coadministration of a single dose of islatravir and methadone was generally well tolerated. Single-dose islatravir did not affect steady-state methadone pharmacokinetics in a clinically meaningful way., (© 2024 Sirtsei Pharmaceuticals, Inc. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

Introduction: Chronic pain (CP) affects 35.0%-51.3% of the UK population, with 67%-88% reporting sleep disturbances. Cannabis-based medicinal products (CBMPs) have shown therapeutic potential in managing CP. Evidence suggests poor sleep worsens pain perception; therefore, this study aimed to assess patient-reported outcome measures (PROMs) following CBMP treatment in CP patients with and without co-morbid sleep impairment., Methods: A prospective cohort study of CP patients from the UK Medical Cannabis Registry was conducted. Participants were separated by baseline single-item sleep quality scale (SQS) score into sleep impaired (SQS ≤3) and unimpaired (SQS ≥4) cohorts. The primary outcome assessed changes in PROMs from baseline to 1-, 3-, 6-, and 12-months. Participants completed the following: SQS, General Anxiety Disorder-7, EQ-5D-5L, Brief Pain Inventory (BPI), and Short-Form McGill Pain Questionnaire-2. Significance was defined as p < 0.050., Results: 1139 participants met the inclusion criteria (sleep impaired: n = 517, 45.4%; sleep unimpaired: n = 622, 54.61%). The sleep impaired cohort showed improvements in all PROMs at each follow-up (p < 0.010). The sleep unimpaired cohort showed similar results (p < 0.050), except in SQS and ED-5Q-5L: self-care and anxiety/depression scores (p > 0.050). However, the sleep impaired cohort observed greater improvements in BPI pain severity (p < 0.050) and SQS (p < 0.001) than the sleep unimpaired cohort at all follow-ups. 2817 adverse events were self-reported between both cohorts (p = 0.197)., Discussion: These findings align with literature that shows associated improvements in pain outcomes following CBMP administration. Sleep impaired individuals were more likely to experience greater pain severity improvements. However, this was not confirmed on multivariate logistic regression analysis and instead may be confounded by baseline pain severity., Conclusion: Whilst these results show promise for the effects of CBMPs on CP, they must be examined within the limitations of the study design. These findings provide further evidence to support the design of subsequent randomized controlled trials to verify causality between CBMPs and pain outcomes., (© 2024 The Author(s). Pain Practice published by Wiley Periodicals LLC on behalf of World Institute of Pain.)

Purpose: Youth who are Not in Education, Employment, or Training (NEET) are at risk for numerous long-term occupational, social, and mental health-related sequelae. The aim of the present study was to investigate mediated pathways from early life risk factors to NEET status in early adulthood, with a particular focus on the role of the family environment during adolescence., Methods: Participants were 6,403 respondents from the National Longitudinal Survey of Children and Youth, who were aged 10-11 years in cycles 1 (1994-1995) to 4 (2000-2001). Parents reported on indicators of early life adversity as well as parent-child conflict at age 12-13. Adolescents reported on their mental health and behaviour at age 14-15. NEET status was assessed at age 24 using tax information from the linked T1 Family File. Indirect pathways from childhood exposures, through adolescent factors, to NEET status in young adulthood were assessed via mediation analysis., Results: At age 10/11, living with a single parent, low household income, stressful life events, and having a parent with a chronic condition were associated with greater likelihood of being NEET at age 24; parents' social support was negatively associated with NEET. These associations were mediated through parental depression at age 10/11, parent-child conflict at age 12/13, and adolescent mental health and behaviour at age 14/15., Discussion: Our results add to a large body of literature linking family stressors, parental depression, parent-child interaction, and adolescent behaviour symptoms, suggesting a chain of influence through these factors toward young adult marginalization from the labour market., (Copyright © 2024 Society for Adolescent Health and Medicine. All rights reserved.)

Developmental plasticity refers to conditions and circumstances that increase phenotypic variability. In infancy, plasticity expands and contracts depending on domains of functioning, developmental history, and timing. In terms of language processing, infants attend to and discriminate both native and non-native phonetic contrasts, but selectively attune to their native phonemes by the end of the first postnatal year. However, relevant studies have excluded factors regarded as promoters of attention such as infant-directed (ID) speech, synchronous multimodal presentations, and female speakers. Here we investigated whether English-learning 11-month-olds would discriminate a non-native phonetic contrast while manipulating these factors. Results showed significant discrimination of the non-native contrast, regardless of speech register, provided that they were presented by a dynamic female speaker. Interestingly, when a static object or a dynamic male ID speaker replaced the female, no significant discrimination was found. These results show infants to be capable of discriminating non-native phonetic contrasts in an enhanced context at an age when they have been characterized as not being able to do so. Synchronized, multimodal information from female speakers allowed infants to perceive difficult non-native phonemes, highlighting the importance of an ecologically valid context for studying speech perception and language learning in early development., (© 2024 The Author(s). Infancy published by Wiley Periodicals LLC on behalf of International Congress of Infant Studies.)

Introduction: We sought to develop clinical guidelines within our multidisciplinary Breast Center to support decision-making for managing high-risk breast lesions. The objective is to describe the process used to develop these guidelines and assess perceived acceptability., Methods: We recruited clinical stakeholders to identify key "high-risk" topics. Stakeholder groups (surgery, radiology, pathology) met separately to review the topics, leveraging existing literature reviews and best available evidence. Guidelines were initially developed in 2015 and updated in 2019. We surveyed breast clinical team members in 2023 regarding the perceived acceptability of the guidelines and summarized the data., Results: We created clinical guidelines to address the management of atypical ductal hyperplasia, flat epithelial atypia, atypical lobular hyperplasia/lobular carcinoma in situ, radial scar/complex sclerosing lesion, and papillomas. Key guideline components included process for radiologic-pathologic correlation, patient disposition after biopsy (surgical referral needed, follow-up imaging recommended), recommendation for the role of surgical excision, and recommendation regarding imaging follow-up if excision not performed. Forty clinical team members (66% [40/60] response rate) completed the acceptability survey from varied disciplines. Most (78%) were aware of the guidelines. Respondents rated the recommendations for disposition after biopsy, surgical management, and follow-up imaging as the most helpful components. Most (> 80%) rated them to be very/extremely useful., Conclusion: We leveraged input from key stakeholders to develop clinical guidelines to support the multidisciplinary management of patients with high-risk breast lesions. Our guidelines have been successfully implemented across our academic and community practice. Future steps will assess the impact of implementation on clinical outcomes., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Assess university students' SARS-CoV-2 antibody seroprevalence and mitigation behaviors over time. Participants: Randomly selected college students ( N  = 344) in a predominantly rural Southern state. Methods: Participants provided blood samples and completed self-administered questionnaires at three timepoints over the academic year. Adjusted odds ratios and 95% confidence intervals were estimated from logistic regression analyses. Results: SARS-CoV-2 antibody seroprevalence was 18.2% in September 2020, 13.1% in December, and 45.5% in March 2021 (21% for those with no vaccination history). SARS-CoV-2 antibody seroprevalence was associated with large social gatherings, staying local during the summer break, symptoms of fatigue or rhinitis, Greek affiliation, attending Greek events, employment, and using social media as the primary COVID-19 information source. In March 2021, seroprevalence was associated with receiving at least one dose of a COVID-19 vaccination. Conclusion: SARS-CoV-2 seroprevalence was higher in this population of college students than previous studies. Results can assist leaders in making informed decisions as new variants threaten college campuses.

Objective: The purpose of this review is to systematically assess primary research publications on known genetic variants, which modify the risk for symptoms or dysfunction persisting 30 days or more following mild traumatic brain injury (mTBI)., Summary of Review: A search of PubMed and Embase from inception through June 2022 identified 42 studies that associated genetic variants with the presence of symptoms or cognitive dysfunction 30 days or more following mTBI. Risk of bias was assessed for each publication using the Newcastle Ottawa Scale (NOS). Fifteen of the 22 studies evaluating apolipoprotein E ( APOE ) ɛ4 concluded that it was associated with worse outcomes and 4 of the 8 studies investigating the brain-derived neurotrophic factor ( BDNF ) reported the Val66Met allele was associated with poorer outcomes. The review also identified 12 studies associating 28 additional variants with mTBI outcomes. Of these, 8 references associated specific variants with poorer outcomes. Aside from analyses comparing carriers and noncarriers of APOE ɛ4 and BDNF Val66Met, most of the reviewed studies were too dissimilar, particularly in terms of specific outcome measures but also in genes examined, to allow for direct comparisons of their findings. Moreover, these investigations were observational and subject to varying degrees of bias., Conclusions: The most consistent finding across articles was that APOE ɛ4 is associated with persistent post-mTBI impairment (symptoms or cognitive dysfunction) more than 30 days after mTBI. The sparsity of other well-established and consistent findings in the mTBI literature should motivate larger, prospective studies, which characterize the risk for persistent impairment with standardized outcomes in mTBI posed by other genetic variants influencing mTBI recovery., Competing Interests: Michael L. Lipton receives funding from the National Institutes of Health. The remaining authors have no conflicts of interest or funding to declare., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Protein phosphatase 2 regulatory subunit B56δ related neurodevelopmental disorder (PPP2R5D-related NDD) is largely caused by de novo heterozygous missense PPP2R5D variants. We report medical characteristics, longitudinal adaptive functioning, and in-person neurological, motor, cognitive, and electroencephalogram (EEG) activity for PPP2R5D-related NDD. Forty-two individuals (median age 6 years, range = 0.8-25.3) with pathogenic/likely pathogenic PPP2R5D variants were assessed, and almost all variants were missense (97.6%) and de novo (85.7%). Common clinical symptoms were developmental delay, hypotonia, macrocephaly, seizures, autism, behavioral challenges, and sleep problems. The mean Gross motor functional measure-66 was 60.2 ± 17.3% and the mean Revised upper limb module score was 25.9 ± 8.8. The Vineland-3 adaptive behavior composite score (VABS-3 ABC) at baseline was low (M = 61.7 ± 16.8). VABS-3 growth scale value scores increased from baseline in all subdomains (range = 0.6-5.9) after a mean follow-up of 1.3 ± 0.3 years. EEG beta and gamma power were negatively correlated with VABS-3 score; p < 0.05. Individuals had a mean Quality-of-life inventory-disability score of 74.7 ± 11.4. Twenty caregivers (80%) had a risk of burnout based on the Caregiver burden inventory. Overall, the most common clinical manifestations of PPP2R5D-related NDD were impaired cognitive, adaptive function, and motor skills; and EEG activity was associated with adaptive functioning. This clinical characterization describes the natural history in preparation for clinical trials., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: Increased mental health (MH) needs during the COVID-19 pandemic led to the implementation of a novel pediatric Emergency Department Virtual Care (EDVC) service. Our study aimed to describe the pediatric MH patient population that used EDVC by comparing patient-specific factors of those who obtained services virtually to those seen in-person. Method: This retrospective chart review was conducted at a pediatric hospital in Eastern Ontario. Children and youth (aged 3-17) who received virtual or in-person emergency MH services from May to December 2020 were included. Patient demographics, clinical presentation details and disposition were compared between the virtual and in-person groups. Data was analyzed using descriptive statistics. Results: 1104 youth (96.1%) utilized the in-person ED for MH concerns; 45 (3.9%) used EDVC. In-person youth had a higher level of perceived risk (78.9% vs. 41.9%) and were more likely to present with concerns of depression, suicidal ideation, self-harm, or laceration (46.1% vs. 35.6%). Anxiety/situational crises or behavioural issues were more likely to present virtually. Eight patients (17.8%) were redirected to the ED from EDVC. Conclusions: Several patient-specific factors varied between youth seen in-person or virtually for MH concern. Study results can assist with the design and implementation of virtual MH care platforms., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Discrimination disrupts sleep and contributes to race-based health inequities for Black Americans, but less is known about the psychological mechanisms underlying this relation. The current work tests whether emotion invalidation, termed Social Pain Minimization (SPM), mediates discrimination's negative effects on sleep quality. We focus on the experiences of Black Americans because of racism's disproportionate effect on the health outcomes of Black individuals in the U.S., Methods: Four studies with cross-sectional (Studies 1a-1b) and cross-lagged panel designs (Studies 2-3; N total  = 1,176) were used. Discrimination and SPM were assessed with established measures and self-reported sleep quality was assessed with three different operationalizations including the short form Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep-Related Impairment (SRI) subscale and composites of the Insomnia Severity Index (ISI)., Results: Cross-sectional (Studies 1a-1b) and longitudinal mediation analyses (Studies 2-3) indicated discrimination's negative effect on sleep quality partially operated through SPM (Study 1a, 95% CI = [-.24, -.016]); Study 1b, 95% CI = [-.22, -.03]; Study 2, 95% CI = [-.268, -.007]]; Study 3, 95% CI = [-0.043, -.002])., Conclusion: Beyond its direct negative effect on sleep, discrimination also operates through SPM to reduce sleep quality. Emotion invalidation stemming from discrimination damages sleep.

Competing Interests: Disclosure No potential competing interest is reported by the authors. This Information/Education Page did not receive direct funding. Dr Engel's research program has been supported by the Government of Canada's Social Development Partnerships Program (Disability Component), the Canadian Institutes of Health Research, and funds through the University of Manitoba.

Background: The prevalence of suboptimal self-rated health (SRH) and its association with subsequent all-cause and cause-specific mortality after blood or marrow transplantation (BMT) were examined., Methods: Study participants were drawn from the multicenter Blood or Marrow Transplant Survivor Study, and included patients who were transplanted between 1974 and 2014 and had survived ≥2 years after BMT. Participants (aged ≥18 years) completed a survey at a median of 9 years from BMT, and were followed for a median of 5.6 years after survey completion. Survivors provided information on sociodemographic factors, chronic health conditions, health behaviors, and SRH (a single-item measure rated as excellent, very good, good, fair, or poor; excellent, very good, and good SRH were classified as good SRH, and fair and poor were classified as suboptimal SRH). The National Death Index Plus and Accurint databases and medical records provided vital status through December 2021., Results: Of 3739 participants, 784 died after survey completion (21%). Overall, 879 BMT survivors (23.5%) reported suboptimal SRH. Pain, low socioeconomic status, psychological distress, lack of exercise, severe/life-threatening chronic health conditions, post-BMT relapse, obesity, smoking, and male sex were associated with suboptimal SRH. BMT survivors who reported suboptimal SRH had a 1.9-fold increased risk of all-cause mortality (95% confidence interval [CI], 1.6-2.3), 1.8-fold increased risk of recurrence-related mortality (95% CI, 1.4-2.5), and 1.9-fold increased risk of non-recurrence-related mortality (95% CI, 1.4-2.4) compared to those who reported good SRH., Conclusions: This single-item measure could help identify vulnerable subpopulations who could benefit from interventions to mitigate the risk for subsequent mortality., (© 2024 American Cancer Society.)

Purpose: Cardiac dysfunction is the leading cause of mortality among 10-year breast cancer survivors. Limited information regarding long-term risks of cardiac dysfunction after cardiotoxic therapy (anthracyclines, trastuzumab/pertuzumab, radiation) has precluded development of surveillance guidelines for the survivors., Methods: Patients with breast cancer who completed cardiotoxic therapy underwent echocardiographic screening every 2 years. New-onset cardiac dysfunction was defined as left ventricular ejection fraction (LVEF) <50% after cardiotoxic therapy initiation and included early- and late-onset cardiac dysfunction., Results: We evaluated 2,808 echocardiograms in 829 breast cancer survivors; the median age at breast cancer diagnosis was 54.2 years (range, 20.3-86.3); the median follow-up was 8.6 years (1.8-39.8); 39.7% received anthracyclines, 16% received trastuzumab/pertuzumab, 6.2% received both anthracyclines and trastuzumab/pertuzumab, and 38.1% received radiation alone. The cumulative incidence of cardiac dysfunction increased from 1.8% at 2 years to 15.3% at 15 years from cardiotoxic therapy initiation. Multivariable Cox regression analysis identified the following risk factors: non-Hispanic Black race (hazard ratio [HR], 2.15 [95% CI], 1.37 to 3.38), cardiotoxic therapies (anthracyclines: HR, 2.35 [95% CI, 1.25 to 4.4]; anthracyclines and trastuzumab/pertuzumab: HR, 3.92 [95% CI, 1.74 to 8.85]; reference: left breast radiation alone), selective estrogen receptor modulators (HR, 2.0 [95% CI, 1.2 to 3.33]), and precancer hypertension (HR, 3.16 [95% CI, 1.63 to 6.1]). Late-onset cardiac dysfunction was most prevalent among anthracycline- and radiation-exposed patients; early-onset cardiac dysfunction was most prevalent among patients exposed to anthracyclines and trastuzumab/pertuzumab; equal prevalence of both early- and late-onset cardiac dysfunction was observed in trastuzumab-/pertuzumab-exposed patients. Adjusted longitudinal analyses revealed an annual decline in LVEF by 0.29% ( P = .009) over 20 years from breast cancer diagnosis., Conclusion: These findings provide evidence to support echocardiographic surveillance for several years after cardiotoxic therapy and also suggest a need to examine the efficacy of management of cardiovascular risk factors to mitigate risk.