Search

Background: Preventing HIV infections among adolescents and young adults (AYA) is crucial for curtailing the epidemic. Oral pre-exposure prophylaxis (PrEP) is a highly effective prevention method increasingly available to this age group in sub-Saharan Africa but population-based data on awareness and use of PrEP among AYA remains limited., Methods: Analyzing survey data from two rounds of the Rakai Community Cohort Study, an open, population-based cohort, we estimated prevalence ratios associating various sociodemographic characteristics with PrEP awareness and ever-use among 15- to 24-year-olds in south-central Uganda between 2018 and 2023., Results: Most (62.4%, N=3,308/5,301) participants were aware of PrEP as an HIV prevention method but only 1.7% (N=133/7,999) of AYA had ever used it. Among the 35.5% (N=2,838/7,999) of participants meeting PrEP eligibility criteria, ever-use was similarly rare (2.6%, N=75/2,838). Compared to 20 to 24-year-olds, 15 to 19-year-olds were less likely to report awareness (fullyadjPR=0.82, 95%CI 0.78, 0.86) or ever-use (fullyadjPR=0.35, 95%CI 0.21, 0.58). Participants from fishing communities were more likely to be PrEP-aware (fullyadjPR=1.22, 95%CI 1.16, 1.29) or have ever used the prevention method (fullyadjPR=6.07, 95%CI 4.10, 8.98) than those from non-fishing communities., Conclusion: In this cross-sectional study of AYA in Uganda, awareness of PrEP was common but ever-use was rare, even among the third of respondents who were likely PrEP-eligible. This suggests that prevention policies and barriers besides unawareness of the method impede PrEP initiation. Efforts that target those barriers, particularly for adolescents, are critical for reducing HIV incidence among this priority population., Competing Interests: Conflicts of Interest: Authors have no conflicts of interest to report., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

The role of cells of the hematopoietic lineage in fibrosis is controversial. Here we evaluate the contribution of Col I+/CD45+ cells (fibrocytes) to lung fibrosis. Systemic bleomycin treatment was used to induce fibrosis in a bone marrow transplant and two transgenic mouse models. Lung cells from these mice were analyzed by flow cytometry, both immediately upon release from the tissue or following growth on tissue-culture plastic. Fibrotic and control human lung tissue were also used. Fibroblasts and fibrocytes derived from a transgenic mouse model were compared in terms of their morphology, growth, and adhesion to fibronectin. Single cell RNAseq was performed with the analysis focusing on CD45-/Col I+ "fibroblasts" and CD45+/Col I+ "fibrocytes" in control and fibrotic mouse lung tissue. Finally, we inhibited fibrosis in mice using a novel, water-soluble version of caveolin scaffolding domain (CSD) called WCSD. In both mouse and human lung tissue, we observed by flow cytometry a large increase in fibrocyte number and Col I expression associated with fibrosis. In contrast, fibroblast number was not significantly increased. A large increase (>50-fold) in fibrocyte number associated with fibrosis was also observed by single cell RNAseq. In this case, fibroblasts increased 5-fold. Single cell RNAseq also revealed that myofibroblast markers in fibrotic tissue are associated with a cluster containing a similar number of fibrocytes and fibroblasts, not with a resident fibroblast cluster. Some investigators claim that fibrocytes are not present among primary fibroblasts. However, we found that fibrocytes were the predominant cell type present in these cultures prior to passage. Fewer fibrocytes were present after one passage, and almost none after two passages. Our experiments suggest that fibrocytes are crowded out of cultures during passage because fibroblasts have a larger footprint than fibrocytes, even though fibrocytes bind more efficiently to fibronectin. Finally, we observed by flow cytometry that in mice treated with bleomycin and WCSD compared to bleomycin alone, there was a large decrease in the number of fibrocytes present but not in the number of fibroblasts. In summary, fibrocytes are a major collagen-producing cell type that is increased in number in association with fibrosis as well as a major source of myofibroblasts. The common observation that collagen-producing spindle-shaped cells associated with fibrosis are CD45- may be an artifact of passage in cell culture., (Copyright © 2025. Published by Elsevier B.V.)

Background: HIV acquisition among adolescents and young adults (AYA, 15-24 years) is influenced by individual factors, community factors, and public policies and programs. We explored the association of HIV incidence and prevalence with these factors over time among AYA in Rakai, Uganda., Methods: We examined trends over nine survey rounds (2005-2020) of the Rakai Community Cohort Study (RCCS), an open population-based surveillance cohort of individuals living in 30 continuously followed communities in south-central Uganda (n= 35,938 person rounds). We evaluated the associations between individual and community-level factors including HIV community viremia (CV, a measure of community-level ART use and HIV prevalence) and HIV incidence and prevalence. Logistic GEE, Poisson GLM and univariate models were run for HIV prevalence, HIV incidence, and predictors of interest, respectively., Findings: HIV incidence and prevalence declined over time after round 14 (2010-2011) by 66% among AYA men and after round 17 (2015-16) by 60% among young women. Between survey round 11 (2007-2008) and round 19 (2017-2019), the proportions reporting being sexually experienced declined from 58% to 38% in adolescent men (15-19) and from 65% to 35% among adolescent women. The prevalence of VMMC among adolescent men increased from 20% in round 11 to 79% in round 19. At the community-level, we found substantial increases in ART use among PLHIV ( 5% in round 11 and 86% in round 19) with corresponding declines in community viremia. In multivariable analyses, a combination of individual and community-level factors were found to predict HIV incidence and prevalence among AYA, notably VMMC among young men and community viremia among young women., Interpretation: Declines in HIV incidence and prevalence occurred first among AYA men and later among AYA women. These coincided with declines in sexual experience and with public policies that increased access to VMMC and ART. Combination HIV prevention with AYA needs to address risk factors at multiple levels., Funding: This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD, grants R01HD091003, RO1HD070769, R01HD050180, R01 HD074949, and P2CHD058486), the National Institute of Allergy and Infectious Diseases (grants R01AI143333, R01AI110324, U01AI100031, U01AI075115, R01AI110324, R01AI102939, and K01AI125086-01), the National Institute of Mental Health (grants R01MH115799, R01MH107275, R01 MH128232, F31MH134699), and the Division of Intramural Research of the National Institute for Allergy and Infectious Diseases., Author Contributions: SAG, JSS, ISC, TL, YW, ES, SH, AND PK conceived and designed the study. ISC, JT and YW oversaw data cleaning and statistical analysis and directly accessed and verified the underlying data reported in the manuscript. AK and DM accessed the data, created the figures for the resubmission and edited the text. AK and DTL, FN, DS, JK, MKG, MJW, LWC, FMS oversaw data collection. All authors had full access to the data in the study, participated in the interpretation of data and revising the manuscript, and had final responsibility for the decision to submit for publication., Research in Context: Evidence before this study: Age-specific rates of HIV incidence are often highest among AYA and particularly young women. Risk factors for HIV infection among AYA include earlier sexual initiation, multiple partners, and inconsistent condom use. Combination prevention including community-wide uptake of ART and male medical circumcision has been associated with declines in HIV incidence in Rakai, Uganda in the overall population. 1,2 A 2019 review of HIV incidence among adolescent girls and young women from 10 high-prevalence African countries found that few studies have examined incidence over time, and among those that there was limited evidence of incidence declines. 3 Added value of this study: Using data from 2005-2020 and the Rakai Community Cohort Study (RCCS) in southcentral Uganda, we found evidence that community-level factors including community viremia and ART use, VMMC among young men, and declines in sexual experience were associated with lower risk of HIV acquisition and seroprevalent infection among AYA. Declining HIV incidence and prevalence over time among AYA coincided with policy changes expanding access to ART and VMMC. Implications of all the available evidence: Age of sexual initiation and community-level factors play critical roles in HIV transmission in Rakai and in declines over time in youth HIV incidence and prevalence. HIV prevention for AYA needs to address individual factors and public policies to improve access to ART and VMMC.

Background: Obstetric hemorrhage is the leading cause of maternal mortality and severe maternal morbidity (SMM) in Maryland and nationally. Currently, through a quality collaborative, the state is implementing the Alliance for Innovation on Maternal Health (AIM) patient safety bundle on obstetric hemorrhage., Objective: To describe SMM events contributed by obstetric hemorrhage and their preventability in Maryland., Study Design: This cross-sectional study used data from hospital-based SMM surveillance and review program in Maryland. Hospital-based SMM criteria include admission to an intensive care unit and/or transfusion of 4 or more units of blood products (of any type) during pregnancy or within 42 days postpartum. A total of 193 obstetric hemorrhage events that met the surveillance definition were identified in hospitals participating in SMM surveillance since inception on August 1, 2020 until December 31, 2022. We compared patient and delivery characteristics, practices done well, and recommendations for care improvement among patients with severe obstetric hemorrhage deemed preventable and non-preventable by hospital-based review committees. For obstetric hemorrhage events deemed preventable, we further identified factors that contributed to the SMM outcome at the provider, system, and patient levels., Results: Uterine atony was the leading cause of obstetric hemorrhage events (37.8%), followed by uterine rupture, laceration and intra-abdominal bleeding (23.8%). Sixty-six (34.2%) obstetric hemorrhage events were preventable. Patients with preventable obstetric hemorrhage were significantly more likely to have an emergency than planned cesarean delivery and less likely to have a placental complication or >1500 mL blood loss volume. Hospital-based review committees determined that 81.8%, 30.3%, and 22.7% of preventable events could have been prevented or made less severe through changes to provider, system, or patient factors, respectively. Recommendations following event reviews aligned with the Alliance for Innovation on Maternal Health Obstetric Hemorrhage Patient Safety Bundle, particularly regarding elements in the Recognition and Prevention and Response domains., Conclusion: About one-third of SMM events contributed by obstetric hemorrhages were deemed preventable. Of AIM bundle elements, assessing hemorrhage risk on admission to labor and delivery, peripartum, and upon transition to postpartum care together with rapid, unit-standardized management of hemorrhage are likely to benefit more than half of patients with preventable SMM contributed by obstetric hemorrhage., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Background: Ultrasound (US) has emerged as a promising supplement to electrodiagnostic studies (EDX) in the diagnosis of cubital tunnel syndrome (CuTS) and has potential to be performed by novice operators. Our objective is to understand the discrepancies in assessment between the two modalities and to assess the utility of US in CuTS diagnosis by a novice operator., Methods: Patients who presented to a single tertiary academic medical center and clinically diagnosed with CuTS were prospectively enrolled. Electrodiagnostic studies were performed along with US measurements of the cross-sectional area (CSA) of the ulnar nerve by both a board-certified physiatrist and novice operator. Electrodiagnostic study and US outcomes were compared among four diagnostic impression groups: EDX-/US-, EDX+/US-, EDX-/US+, and EDX+/US+., Results: Sixteen patients were classified as abnormal by both EDX and US, 14 were classified abnormal by US only, 3 were classified abnormal by EDX only, and 6 were classified normal by both EDX and US ( P = .008, K = 0.14). The EDX+/US+ group had a significantly reduced sensory amplitude compared with the EDX-/US+ ( P = .04) group. Diagnostic classifications between a board-certified physiatrist and novice operator were in moderate agreement (K = 0.58, P = .08)., Conclusions: Ultrasound detected a greater proportion of patients as abnormal than EDX. A subset of patients with clinical diagnoses of CuTS had normal sensory amplitudes but increased maximum nerve CSAs. Competency in US may be easily acquired with minimal training, suggesting its potential to be extended for use by other members of the health care team., 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.

We present a concise review of the background, pitfalls, and potential solutions for the noninvasive evaluation and continuous tracking of cardiac autonomic nervous system activity (ANSA), using surface-ECG-accessible parameters, including heart rate (HR), heart-rate variability (HRV), and cardiac repolarization. These parameters have provided insights into the dynamics of cardiac ANSA in controlled experiments and have proved useful in risk assessment with respect to sudden cardiac death and all-cause mortality in some patient populations, as well as in implantable device programming. Yet attempts to translate these parameters from the laboratory environment to ambulatory settings have been hampered by the presence of multiple uncontrolled factors, including changes in blood pressure, body position, physical activity, and respiration frequency. We show that a single-parameter-based, simplified cardiac ANSA evaluation in an uncontrolled ambulatory setting could be inaccurate, and we discuss several approaches to improve accuracy. Discerning cardiac ANSA effects in uncontrolled ambulatory environments requires tracking multiple physiological processes, preferably using multisensor, multiparametric monitoring and controlling some physiological variables (e.g., respiration frequency); data fusion and machine-learning-based analytics are instrumental for developing more accurate personalized ANSA evaluation., Competing Interests: Declaration of competing interest Dr. Shusterman has patents in the area of personalized ECG monitoring. He also has a significant (>5 %) ownership interest in PinMed, Inc., which develops physiological monitoring systems., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: In sub-Saharan Africa, pediatric and adult treatment programs have not met the needs of youth living with HIV (15-24 years), whose enrollment in antiretroviral treatment (ART) programs is much lower than that of adults. To inform targeted interventions, we analyzed factors associated with ART use among youth in Uganda., Methods: Data were from 42 communities between 2011 and 2020 (5 survey rounds) from the Rakai Community Cohort Study, an open, population-based cohort. Among youth, we assessed trends in ART use over time and demographic characteristics and sexual behaviors associated with ART use., Results: Youth (N = 1518) contributed 2101 person-visits. ART coverage increased over time with 8% of men and 11% of women on ART in 2011-2013 and 45% and 68%, respectively, on ART in 2018-2020 (AORwomen vs. men=2.57; 95% CI: 1.72 to 3.84). Youth with 2 or more sexual partners compared with youth with 0-1 sexual partner were less likely to be on ART (men AOR = 0.40; 0.19-0.82; women AOR = 0.54; 0.41-0.72). Youth who reported consistent condom use were more likely to be on ART (men AOR = 2.94; 95% CI: 1.14 to 7.57; women AOR = 1.70; 95% CI: 1.00 to 2.88)., Conclusions: In this longitudinal study, ART use among youth increased over time, yet at 63% remained well below UNAIDS 95-95-95 goals, thus depriving many of lifesaving treatment. Those engaging in fewer protective sexual behaviors had lower ART use, thus further increasing risk of future HIV transmission. Targeted efforts are needed to ensure rapid initiation of ART and continued engagement among this vulnerable population., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Risk perception, its relationship to preventive health behaviors and other factors (e.g., direct experience of a disease) are important for determining effective targets for disease prevention. Whether these relationships are the same for various diseases has not been well-researched. Drawing on a holistic model of risk perception, this study compares levels of perceived risk for COVID-19 and HIV in a rural Zambian community, examines hypothesized correlates of perceived risk, and evaluates whether higher perceived risk and/or its correlates are associated with practicing preventive behaviors for each disease. The sample included 118 adults participating in a larger study of families affected by HIV. Via surveys, information about risk perception, preventive behaviors, knowledge about, trust in information sources, direct experience and hearing about each disease, and prosociality, were collected. For each disease, perceived risk was not related to its preventive behaviors. Levels of perceived risk for COVID-19 and HIV differed significantly, as did their correlates. Having trusted sources of information about HIV was related to higher perceived risk of HIV. Direct experience of COVID-19 was related to higher perceived risk of COVID-19, but only at a level of interest. Although practicing preventive behaviors for each condition was related to higher levels of knowledge about each disease at a level of interest, willingness to engage in behavior beneficial to others (prosociality) was significantly related only to COVID-19 preventive behaviors. Different diseases provoke different levels of perceived risk and engagement with preventive behaviors and may be correlated with distinct factors. These differences may be due to history of experience with a disease, as well as cultural factors., Competing Interests: Declarations. Ethical Approval: All procedures performed in this study involving human participants were in accordance with the ethical standards of the University of Houston and Macha Research Trust Institutional Review Boards, with the National Health Research Authority of Zambia, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed Consent: Written informed consent was obtained from all individual participants included in the study. Statement Regarding the Welfare of Animals (as Appropriate): Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Exploration of the relationship between mental health constructs and physical health constructs can help practitioners better understand the mental health of vulnerable populations, such as college students in the United States. The purpose of this exploratory study was to investigate the connection between mental well-being and health literacy of US college students. Participants: The sample included 410 undergraduate students (63% white; 71% female) attending universities across the United States. Methods: Participants completed the All Aspects of Health Literacy Scale and the Warwick-Edinburgh Mental Well-being Scale. Univariate and bivariate statistics were observed for all study variables, and three linear regression models were run to see whether functional, communicative, and/or critical health literacy scores predicted mental well-being. Conclusions: Findings suggest that health literacy was associated with improved mental well-being among US college students, which has implications for health programming at US universities, such as the coordination of physical and mental healthcare.

Health literacy (HL) is essential to understanding health information and achieving health goals. Unfortunately, limited information is available on how parent HL impact child health outcomes. This is critical to understand in areas of the world where access to healthcare services is limited or unavailable. Thus, the purpose of this study was to assess the moderating influence of access to care on the relationship between parent HL and child health outcomes in Mexico. Using a geographically stratified convenience sample survey design, we gathered a sample of 373 parent-child dyads throughout Mexico in August of 2021. Using the HLS-Q12, the Warwick-Edinburgh Mental Wellbeing Scale, healthcare access questions developed by Levy and Janke, a single-item self-report overall health measure, and questions about substance use frequency, we found that parent HL was positively associated with youth mental wellbeing and overall health. Limited healthcare access was associated with increased youth cigarette, marijuana and alcohol use. Our results indicate that efforts to increase parent HL may be effective in improving youth health behaviors and outcomes., (© The Author(s) 2024. Published by Oxford University Press. 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.)

Background: Netball, with its dynamic movements, poses a high injury risk, notably to the ankles and knees. This study examined the injury knowledge and attitudes of semi-professional netball players in the Western Cape, South Africa., Methods: In this study 117 semi-professional female netball players from eight clubs in the Western Cape district were conveniently sampled. A self-administered researcher-generated questionnaire collected data on the players' sociodemographic characteristics, as well as their knowledge and attitudes regarding netball injuries. Independent samples t-test, Pearson's correlation coefficient, and the χ 2 tests were employed for data analyses., Results: Results showed that most players (62.4%) had good knowledge of injury prevention and recovery, though a minority held negative attitudes (39.0% and 29.0%, respectively). Those with over three years of experience demonstrated superior knowledge (85.7%) and more positive attitudes (61.9% and 71.4%). Conversely, a minority (37.6%) exhibited poor knowledge, while a majority (61.00%) displayed positive attitudes. Furthermore, a moderate positive correlation (r=0.552; P<0.001) was observed between overall knowledge and attitudes towards injury prevention and recovery., Conclusions: While most semi-professional netball players possess adequate injury knowledge, those with longer experience show more positive attitudes. Establishing educational programs emphasizing injury prevention and recovery could benefit players, especially those starting later in life, promoting both knowledge and positive attitudes towards injury management.

Introduction: Accurate information on context and implementation of public health interventions is necessary to replicate, adapt, and scale effective interventions and to interpret evaluations. Reporting the context and implementation of water, sanitation, and hygiene (WASH) interventions has been inconsistent and incomplete., Methods: To improve the reporting of WASH interventions, we developed the Template for Intervention Description and Replication for WASH (TIDieR-WASH) checklist and guide, by adapting and expanding the original TIDieR guide. We performed a scoping review of existing implementation reporting guidelines, and of current implementation reporting in WASH evaluations, to develop a list of candidate items to include in this checklist. We then used a 4-stages of review by international experts to reach consensus., Results: The resulting 14-item checklist comprises: a ) name, b ) theory of change, c ) prior evidence, d ) location and setting, e ) context, f ) suitability, g ) implementers, h ) recipients, i ) targeting, j ) activities, k ) intervention dose, l ) fidelity, m ) costs, and n ) materials. Definitions, explanations, examples, and instructions for use are reported in this article., Discussion: The checklist can be applied to all types of evaluations of WASH interventions, including direct service provision, behavior change, and systems strengthening interventions. We deliberately developed this guidance document to be accessible and relevant to practitioners and researchers. Adoption of this checklist will support transparent reporting of WASH implementation for research and practice. As with other sectors that have used TIDieR checklists, clear implementation reporting can assist with evidence synthesis, adaptation, and policy guidance. https://doi.org/10.1289/EHP14780.

In 2022-2024, three outbreaks of sheeppox (SPP) were reported in the European Union. These occurred in Spain, Bulgaria, and Greece and had serious economic consequences due to animal losses and trade restrictions. Five sheeppox virus (SPPV) whole-genome sequences (WGSs) were determined from samples collected during these outbreaks and analyzed in the context of all other published WGSs. Sheeppox virus strains can be divided in two, or possibly three, main groups. The isolates from the recent outbreaks belong to clade A2, which includes strains historically circulating in the Middle East and Northern Africa. Sequence divergence was low among the isolates that caused the recent European outbreaks. These results highlight the need for more regular and dense surveillance in under-sampled areas and the use of WGS to increase the chance of pinpointing the origin of an introduction, identifying potential introduction routes, and providing insights into SPPV evolution., (© 2024. The Author(s).)

Clinical trials in metabolic dysfunction-associated steatohepatitis (MASH, formerly known as nonalcoholic steatohepatitis) require histologic scoring for assessment of inclusion criteria and endpoints. However, variability in interpretation has impacted clinical trial outcomes. We developed an artificial intelligence-based measurement (AIM) tool for scoring MASH histology (AIM-MASH). AIM-MASH predictions for MASH Clinical Research Network necroinflammation grades and fibrosis stages were reproducible (κ = 1) and aligned with expert pathologist consensus scores (κ = 0.62-0.74). The AIM-MASH versus consensus agreements were comparable to average pathologists for MASH Clinical Research Network scores (82% versus 81%) and fibrosis (97% versus 96%). Continuous scores produced by AIM-MASH for key histological features of MASH correlated with mean pathologist scores and noninvasive biomarkers and strongly predicted progression-free survival in patients with stage 3 (P < 0.0001) and stage 4 (P = 0.03) fibrosis. In a retrospective analysis of the ATLAS trial (NCT03449446), responders receiving study treatment showed a greater continuous change in fibrosis compared with placebo (P = 0.02). Overall, these results suggest that AIM-MASH may assist pathologists in histologic review of MASH clinical trials, reducing inter-rater variability on trial outcomes and offering a more sensitive and reproducible measure of patient responses., (© 2024. The Author(s).)

Ribosomal RNA (rRNA) genes exist in multiple copies arranged in tandem arrays known as ribosomal DNA (rDNA). The total number of gene copies is variable, and the mechanisms buffering this copy number variation remain unresolved. We surveyed the number, distribution, and activity of rDNA arrays at the level of individual chromosomes across multiple human and primate genomes. Each individual possessed a unique fingerprint of copy number distribution and activity of rDNA arrays. In some cases, entire rDNA arrays were transcriptionally silent. Silent rDNA arrays showed reduced association with the nucleolus and decreased interchromosomal interactions, indicating that the nucleolar organizer function of rDNA depends on transcriptional activity. Methyl-sequencing of flow-sorted chromosomes, combined with long read sequencing, showed epigenetic modification of rDNA promoter and coding region by DNA methylation. Silent arrays were in a closed chromatin state, as indicated by the accessibility profiles derived from Fiber-seq. Removing DNA methylation restored the transcriptional activity of silent arrays. Array activity status remained stable through the iPS cell re-programming. Family trio analysis demonstrated that the inactive rDNA haplotype can be traced to one of the parental genomes, suggesting that the epigenetic state of rDNA arrays may be heritable. We propose that the dosage of rRNA genes is epigenetically regulated by DNA methylation, and these methylation patterns specify nucleolar organizer function and can propagate transgenerationally.

The plasma membrane protein caveolin-1 (CAV-1) regulates signaling by inhibiting a wide range of kinases and other enzymes. Our previous study demonstrated that the downregulation of CAV-1 in psoriatic epidermal cells contributes to inflammation by enhancing JAK/STAT signaling, cell proliferation, and chemokine production. Administration of the CAV-1 scaffolding domain (CSD) peptide suppressed imiquimod (IMQ)-induced psoriasis-like dermatitis. To identify an optimal therapeutic peptide derived from CAV-1, we have compared the efficacy of CSD and subregions of CSD that have been modified to make them water soluble. We refer to these modified peptides as sCSD, sA, sB, and sC. In IMQ-induced psoriasis-like dermatitis, while all four peptides showed major beneficial effects, sB caused the most significant improvements of skin phenotype and number of infiltrating cells, comparable or superior to the effects of sCSD. Phosphorylation of STAT3 was also inhibited by sB. Furthermore, sB suppressed angiogenesis both in vivo in the dermis of IMQ-induced psoriasis mice and in vitro by blocking the ability of conditioned media derived from CAV-1-silenced keratinocytes to inhibit tube formation by HUVEC. In conclusion, sB had similar or greater beneficial effects than sCSD not only by cytokine suppression but by angiogenesis inhibition adding to its ability to target psoriatic inflammation., (© 2024. The Author(s).)

The complex and dynamic cellular composition of the human endometrium remains poorly understood. Previous endometrial single-cell atlases profiled few donors and lacked consensus in defining cell types. We introduce the Human Endometrial Cell Atlas (HECA), a high-resolution single-cell reference atlas (313,527 cells) combining published and new endometrial single-cell transcriptomics datasets of 63 women with and without endometriosis. HECA assigns consensus and identifies previously unreported cell types, mapped in situ using spatial transcriptomics and validated using a new independent single-nuclei dataset (312,246 nuclei, 63 donors). In the functionalis, we identify intricate stromal-epithelial cell coordination via transforming growth factor beta (TGFβ) signaling. In the basalis, we define signaling between fibroblasts and an epithelial population expressing progenitor markers. Integration of HECA with large-scale endometriosis genome-wide association study data pinpoints decidualized stromal cells and macrophages as most likely dysregulated in endometriosis. The HECA is a valuable resource for studying endometrial physiology and disorders, and for guiding microphysiological in vitro systems development., (© 2024. The Author(s).)

Postprandial dyslipidemia is commonly present in people with type 2 diabetes and obesity and is characterized by overproduction of apolipoprotein B48-containing chylomicron particles from the intestine. Peripheral serotonin is emerging as a regulator of energy homeostasis with profound implications for obesity; however, its role in dietary fat absorption and chylomicron production is unknown. Chylomicron production was assessed in Syrian golden hamsters by administering an olive oil gavage and IP poloxamer to inhibit lipoprotein clearance. Administration of serotonin or selective serotonin reuptake inhibitor, fluoxetine, increased postprandial plasma triglyceride (TG) and TG-rich lipoproteins. Conversely, inhibiting serotonin synthesis pharmacologically by p-chlorophenylalanine (PCPA) led to a reduction in both the size and number of TG-rich lipoprotein particles, resulting in lower plasma TG and apolipoprotein B48 levels. The effects of PCPA occurred independently of gastric emptying and vagal afferent signaling. Inhibiting serotonin synthesis by PCPA led to increased TG within the intestinal lumen and elevated levels of TG and cholesterol in the stool when exposed to a high-fat/high-cholesterol diet. These findings imply compromised fat absorption, as evidenced by reduced lipase activity in the duodenum and lower levels of serum bile acids, which are indicative of intestinal bile acids. During the postprandial state, mRNA levels for serotonin receptors (5-HTRs) were upregulated in the proximal intestine. Administration of cisapride, a 5-HT4 receptor agonist, alleviated reductions in postprandial lipemia caused by serotonin synthesis inhibition, indicating that serotonin controls dietary fat absorption and chylomicron secretion via 5-HT4 receptor., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. 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. See the journal About page for additional terms.)

Background: Participant recruitment in rural and hard-to-reach (HTR) populations can present unique challenges. These challenges are further exacerbated by the need for low-cost recruiting, which often leads to use of web-based recruitment methods (eg, email, social media). Despite these challenges, recruitment strategy statistics that support effective enrollment strategies for underserved and HTR populations are underreported. This study highlights how a recruitment strategy that uses email in combination with follow-up, mostly phone calls and email reminders, produced a higher-than-expected enrollment rate that includes a diversity of participants from rural, Appalachian populations in older age brackets and reports recruitment and demographic statistics within a subset of HTR populations., Objective: This study aims to provide evidence that a recruitment strategy that uses a combination of email, telephonic, and follow-up recruitment strategies increases recruitment rates in various HTR populations, specifically in rural, older, and Appalachian populations., Methods: We evaluated the overall enrollment rate of 1 recruitment arm of a larger study that aims to understand the relationship between genetics and substance use disorders. We evaluated the enrolled population's characteristics to determine recruitment success of a combined email and follow-up recruitment strategy, and the enrollment rate of HTR populations. These characteristics included (1) enrollment rate before versus after follow-up; (2) zip code and county of enrollee to determine rural or urban and Appalachian status; (3) age to verify recruitment in all eligible age brackets; and (4) sex distribution among age brackets and rural or urban status., Results: The email and follow-up arm of the study had a 17.4% enrollment rate. Of the enrolled participants, 76.3% (4602/6030) lived in rural counties and 23.7% (1428/6030) lived in urban counties in Pennsylvania. In addition, of patients enrolled, 98.7% (5956/6030) were from Appalachian counties and 1.3% (76/6030) were from non-Appalachian counties. Patients from rural Appalachia made up 76.2% (4603/6030) of the total rural population. Enrolled patients represented all eligible age brackets from ages 20 to 75 years, with the 60-70 years age bracket having the most enrollees. Females made up 72.5% (4371/6030) of the enrolled population and males made up 27.5% (1659/6030) of the population., Conclusions: Results indicate that a web-based recruitment method with participant follow-up, such as a phone call and email follow-up, increases enrollment numbers more than web-based methods alone for rural, Appalachian, and older populations. Adding a humanizing component, such as a live person phone call, may be a key element needed to establish trust and encourage patients from underserved and rural areas to enroll in studies via web-based recruitment methods. Supporting statistics on this recruitment strategy should help researchers identify whether this strategy may be useful in future studies and HTR populations., (©Tabitha Milliken, Donielle Beiler, Samantha Hoffman, Ashlee Olenginski, Vanessa Troiani. Originally published in JMIR Formative Research (https://formative.jmir.org), 22.08.2024.)

Esophageal adenocarcinoma (EAC) is a highly lethal cancer of the upper gastrointestinal tract with rising incidence in western populations. To decipher EAC disease progression and therapeutic response, we performed multiomic analyses of a cohort of primary and metastatic EAC tumors, incorporating single-nuclei transcriptomic and chromatin accessibility sequencing, along with spatial profiling. We identified tumor microenvironmental features previously described to associate with therapy response. We identified five malignant cell programs, including undifferentiated, intermediate, differentiated, epithelial-to-mesenchymal transition, and cycling programs, which were associated with differential epigenetic plasticity and clinical outcomes, and for which we inferred candidate transcription factor regulons. Furthermore, we revealed diverse spatial localizations of malignant cells expressing their associated transcriptional programs and predicted their significant interactions with microenvironmental cell types. We validated our findings in three external single-cell RNA-seq and three bulk RNA-seq studies. Altogether, our findings advance the understanding of EAC heterogeneity, disease progression, and therapeutic response., Competing Interests: E.M.V.: Advisory/Consulting: Enara Bio, Manifold Bio, Monte Rosa, Novartis Institute for Biomedical Research, Serinus Bio, TracerDx Research support: Novartis, BMS, Sanofi, NextPoint Equity: Tango Therapeutics, Genome Medical, Genomic Life, Enara Bio, Manifold Bio, Microsoft, Monte Rosa, Riva Therapeutics, Serinus Bio, Syapse, TracerDx Travel reimbursement: None Patents: Institutional patents filed on chromatin mutations and immunotherapy response, and methods for clinical interpretation; intermittent legal consulting on patents for Foaley & Hoag Editorial Boards: Science Advances A.J.A. has consulted for Anji Pharmaceuticals, Affini-T Therapeutics, Arrakis Therapeutics, AstraZeneca, Boehringer Ingelheim, Kestrel Therapeutics, Merck & Co., Inc., Mirati Therapeutics, Nimbus Therapeutics, Oncorus, Inc., Plexium, Quanta Therapeutics, Revolution Medicines, Reactive Biosciences, Riva Therapeutics, Servier Pharmaceuticals, Syros Pharmaceuticals, T-knife Therapeutics, Third Rock Ventures, and Ventus Therapeutics. A.J.A. holds equity in Riva Therapeutics and Kestrel Therapeutics. A.J.A. has research funding from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Deerfield, Inc., Eli Lilly, Mirati Therapeutics, Nimbus Therapeutics, Novartis, Novo Ventures, Revolution Medicines, and Syros Pharmaceuticals.

Suicide negatively impacts societies worldwide. A particular area of concern is the prevalence of suicide among Latinx youth, as research indicates that suicide behaviors among Latinx in the United States and youth in Latin America have increased drastically over the last decade. Reducing suicide stigma is a key factor in promoting youth help-seeking behaviors regarding suicidality. Previous research suggests that a relationship with a trusted adult may influence the likelihood of an adolescent contacting a suicide crisis line. Our study seeks to further the research of how parents can influence youth perceptions of suicide by studying the relationship between parent and child suicide stigma. Data were collected from parent-child dyads throughout Mexico. The Stigma of Suicide Scale Short Form was used to measure suicide stigma among adult and youth participants independently. Results suggest that parent suicide stigma was a significant predictor of youth suicide stigma, that male youth in our sample had higher suicide stigma than female youth, and that access to healthcare services was associated with lower suicide stigma. Results are discussed considering unique cultural factors in Mexico such as familismo. If future research reinforces the findings of this study, suicide stigma programs might be more effective if targeted at the entire family unit rather than just adolescents., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interests with respect to the authorship and/or publication of this article.

Objective. The transcranial magnetic stimulation (TMS) coil induces an electric field that diminishes rapidly upon entering the brain. This presents a challenge in achieving focal stimulation of a deep brain structure. Neuronal elements, including axons, dendrites, and cell bodies, exhibit specific time constants. When exposed to repetitive TMS pulses at a high frequency, there is a cumulative effect on neuronal membrane potentials, resulting in temporal summation. This study aims to determine whether TMS pulse train at high-frequency and subthreshold intensity could induce a suprathreshold response. Approach. As a proof of concept, we developed a TMS machine in-house that could consistently output pulses up to 250 Hz, and performed experiments on 22 awake rats to test whether temporal summation was detectable under pulse trains at 100, 166, or 250 Hz. Main results. Results revealed that TMS pulses at 55% maximum stimulator output (MSO, peak d I /d t = 68.5 A/ μ s at 100% MSO, pulse width = 48 μ s) did not induce motor responses with either single pulses or pulse trains. Similarly, a single TMS pulse at 65% MSO failed to evoke a motor response in rats; however, a train of TMS pulses at frequencies of 166 and 250 Hz, but not at 100 Hz, successfully triggered motor responses and MEP signals, suggesting a temporal summation effect dependent on both pulse intensities and pulse train frequencies. Significance. We propose that the temporal summation effect can be leveraged to design the next-generation focal TMS system: by sequentially driving multiple coils at high-frequency and subthreshold intensity, areas with the most significant overlapping E-fields undergo maximal temporal summation effects, resulting in a suprathreshold response., (Creative Commons Attribution license.)

Objectives: To determine if rates of pin site infection and surgical site infection among patients managed with primary closure after external fixator removal were similar to those allowed to heal secondarily., Design: Retrospective cohort., Setting: Urban/Suburban Academic Level I Trauma Center., Patient Selection Criteria: Patients who had received a lower extremity external fixator for provisional management before definitive fixation of lower extremity fractures were included with pin site wounds closed primarily or allowed to heal by secondary intention., Outcome Measures and Comparisons: The rate of pin tract infection and surgical site infection following primary closure of external fixator pin sites relative to patients whose pin sites were allowed to heal through secondary intention., Results: In total, 256 patients were evaluated: 143 patients (406 pin sites) in the primary closure group and 113 patients (340 in sites) in the secondary closure group. The average age was 49 ± 16 years. Sixty-five percent of included patients were male. There was no difference in pin tract infections between cohorts (primary = 0.5%, secondary = 1.5%, P = 0.26). External fixator duration in the primary closure group was 11.5 ± 8.4 days and 13.0 ± 8.1 days in the secondary closure group (P = 0.15). There was a greater rate of surgical site infections in the secondary intention cohort (15.9% vs. 7.7%, P = 0.047)., Conclusions: There was no difference in pin site infection rate after primary pin site closure relative to patients who were allowed to heal through secondary intention. Furthermore, there was a lower rate of surgical site infection after primary closure. These results challenge the dogma of secondary closure for ex fix pin sites, suggesting that debridement and primary closure is a safe option for management of external fixator pin sites and may impart benefit in decreasing infection risk., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors report no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Many-analysts studies explore how well an empirical claim withstands plausible alternative analyses of the same dataset by multiple, independent analysis teams. Conclusions from these studies typically rely on a single outcome metric (e.g. effect size) provided by each analysis team. Although informative about the range of plausible effects in a dataset, a single effect size from each team does not provide a complete, nuanced understanding of how analysis choices are related to the outcome. We used the Delphi consensus technique with input from 37 experts to develop an 18-item subjective evidence evaluation survey (SEES) to evaluate how each analysis team views the methodological appropriateness of the research design and the strength of evidence for the hypothesis. We illustrate the usefulness of the SEES in providing richer evidence assessment with pilot data from a previous many-analysts study., Competing Interests: We declare we have no competing interests., (© 2024 The Authors.)

Adolescent dating violence is a national public health issue and research suggests that aggressive parenting may predict the likelihood that a child will subsequently experience abuse. The purpose of this study is to examine the effect of parent physical and psychological aggression on adolescent dating violence perpetration and victimization. Data derived from the Future of Families and Child Wellbeing Study resulted in a racially and ethnically diverse sample of adolescents in dating relationships at the age of 15 years ( N  = 952). Utilizing both parent and adolescent data which assessed parenting practices at ages 3, 5, 9, and 15, and adolescent dating violence victimization and perpetration at age 15, we analyzed the data using a latest class analysis. Youth were typologized into three classes: the non-physically aggressive parenting, nonaggressive dating class (Class 1; 16% of youth), the aggressive parenting, nonaggressive dating class (Class 2; 76% of youth), and the aggressive parenting, aggressive dating class (Class 3; 8% of youth). Parents across all three classes utilized high levels of psychologically aggressive parenting. An important finding from this study is that parents' use of both physically and psychologically aggressive parenting only predicted subsequent dating violence victimization and perpetration among a small portion of adolescents. Findings suggest that additional risk factors, including household income and adolescent impulsivity, may help to elucidate pathways to adolescent dating violence. There is also a need to further explore the resiliency factors at play for youth who, despite having experienced both psychologically and physically aggressive parenting across the lifespan, did not experience dating violence victimization or perpetration., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interests with respect to the authorship and/or publication of this article.

Whole-genome sequencing has become the method of choice for bacterial outbreak investigation, with most clinical and public health laboratories currently routinely using short-read Illumina sequencing. Recently, long-read Oxford Nanopore Technologies (ONT) sequencing has gained prominence and may offer advantages over short-read sequencing, particularly with the recent introduction of the R10 chemistry, which promises much lower error rates than the R9 chemistry. However, limited information is available on its performance for bacterial single-nucleotide polymorphism (SNP)-based outbreak investigation. We present an open-source workflow, Prokaryotic Awesome variant Calling Utility (PACU) (https://github.com/BioinformaticsPlatformWIV-ISP/PACU), for constructing SNP phylogenies using Illumina and/or ONT R9/R10 sequencing data. The workflow was evaluated using outbreak data sets of Shiga toxin-producing Escherichia coli and Listeria monocytogenes by comparing ONT R9 and R10 with Illumina data. The performance of each sequencing technology was evaluated not only separately but also by integrating samples sequenced by different technologies/chemistries into the same phylogenomic analysis. Additionally, the minimum sequencing time required to obtain accurate phylogenetic results using nanopore sequencing was evaluated. PACU allowed accurate identification of outbreak clusters for both species using all technologies/chemistries, but ONT R9 results deviated slightly more from the Illumina results. ONT R10 results showed trends very similar to Illumina, and we found that integrating data sets sequenced by either Illumina or ONT R10 for different isolates into the same analysis produced stable and highly accurate phylogenomic results. The resulting phylogenies for these two outbreaks stabilized after ~20 hours of sequencing for ONT R9 and ~8 hours for ONT R10. This study provides a proof of concept for using ONT R10, either in isolation or in combination with Illumina, for rapid and accurate bacterial SNP-based outbreak investigation., Competing Interests: The authors declare no conflict of interest.

Peer-to-peer chain recruitment has been used for descriptive studies, but few intervention studies have employed it. We used this method to enroll sexually active women ages 18 to 25 into an online Pre-Exposure Prophylaxis (PrEP) information and motivation intervention pilot in eThekwini (Durban), South Africa. Seeds (N = 16) were recruited by study staff and randomized to Masibambane, Ladies Chat, a Gender-Enhanced group-based WhatsApp Workshop (GE), or Individual-Access (IA), a control condition that provided participants with online information/motivation materials only. Each seed could recruit up to three women to participate in the same study condition, with an incentive for each enrolled woman; participants in subsequent waves could choose to recruit or not. We evaluated if peer-to-peer recruitment was self-sustaining and resulted in enrolling women who, in subsequent waves, had less contact with the health care system and less knowledge about PrEP than the initial seeds. Over three recruitment waves beyond the seeds, 84 women were recruited. Almost 90% of women became recruiters, with each recruiting on average 1.90 women and 1.26 eligible enrolled women. The approach was successful at reaching women with less education but not women with less health system contact and PrEP knowledge across waves. IA participants had a slightly higher, though non-significantly different, percentage of individuals who became Peer Health Advocates (PHAs) than GE participants and, on average, they recruited slightly more women who enrolled. Our findings demonstrated that peer-to-peer recruitment is a feasible and self-sustaining way to recruit SA young women into a PrEP intervention study., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To determine whether lactate levels were associated with maternal infection and infection-related outcomes in the antepartum, intrapartum, and early postpartum periods., Design: Retrospective, observational cohort., Setting: Eleven hospitals from a single health system., Participants: Women (N = 783) with at least one lactate and blood culture test for obstetric sepsis screening in the antepartum period (n = 154), intrapartum period (n = 348), and early postpartum period (n = 281) from January 2, 2018, to October 21, 2020., Methods: We reported the proportion of participants with adverse outcomes by lactate cut points (≤2.0 and >2.0 mmol/L). We used logistic regression to model the association of infection-related outcomes with lactate levels and calculated receiver operating characteristic curves., Results: Lactate was associated with bacteremia among participants in the antepartum period (odds ratio [OR] = 1.60, 95% confidence interval [CI] [1.00, 2.56]) but not among participants in the intrapartum and early postpartum periods. Higher lactate levels were significantly associated with a composite measure of infection-related outcomes (OR = 1.41, 95% CI [1.14, 1.81]), with no differential association by antepartum, intrapartum, or early postpartum periods. Lactate levels were positively associated with intraamniotic infection in the antepartum period (OR = 1.57, 95% CI [1.06, 1.81]) but not in the intrapartum period. The receiver operating characteristic curve indicated that the lactate threshold of 2.0 mmol/L has poor sensitivity. Overall, participants in the antepartum period had lower lactate values than participants in the intrapartum and early postpartum periods., Conclusion: Lactate levels were not consistently associated with infection-related measures across all periods. We suggest caution when interpreting lactate levels when sepsis is suspected., Competing Interests: Conflict of Interest The authors report no conflicts of interest or relevant financial relationships., (Copyright © 2023 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.)

Metabolic health is highly dependent on intestinal and hepatic handling of dietary and endogenous lipids and lipoproteins. Disorders of lipid and lipoprotein metabolism are commonly observed in patients with insulin resistant states such as obesity, metabolic syndrome, and type 2 diabetes. Evidence from both animal models and human studies indicates that a major underlying factor in metabolic or diabetic dyslipidemia is the overproduction of hepatic and intestinal apolipoprotein (apo)B-containing lipoprotein particles. These particles are catabolized down into highly proatherogenic remnants, which can be taken up into the arterial intima and promote plaque development. Several gut-derived peptides have been identified as key regulators of energy metabolism; one such peptide is the incretin hormone glucagon-like peptide (GLP)-1. Our laboratory has previously demonstrated that GLP-1 can signal both centrally and peripherally to reduce postprandial and fasting lipoprotein secretion. Moreover, we have demonstrated that GLP-1 receptor (GLP-1R) agonists can ameliorate diet-induced dyslipidemia. Recently, we published evidence for a novel vagal neuroendocrine signalling pathway by which native GLP-1 may exert its anti-lipemic effects. Furthermore, we demonstrated a novel role for other gut-derived peptides in regulating intestinal lipoprotein production. Overall, ample evidence supports a key role for GLP-1R on the portal vein afferent neurons and nodose ganglion in modulating intestinal fat absorption and lipoprotein production and identifies other gut-derived peptides as novel regulators of postprandial lipemia. Insights from these data may support identification of potential drug targets and the development of new therapeutics targeting treatment of diabetic dyslipidemia., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

The terrestrial carbon cycle varies dynamically on hourly to weekly scales, making it difficult to observe. Geostationary ("weather") satellites like the Geostationary Environmental Operational Satellite - R Series (GOES-R) deliver near-hemispheric imagery at a ten-minute cadence. The Advanced Baseline Imager (ABI) aboard GOES-R measures visible and near-infrared spectral bands that can be used to estimate land surface properties and carbon dioxide flux. However, GOES-R data are designed for real-time dissemination and are difficult to link with eddy covariance time series of land-atmosphere carbon dioxide exchange. We compiled three-year time series of GOES-R land surface attributes including visible and near-infrared reflectances, land surface temperature (LST), and downwelling shortwave radiation (DSR) at 314 ABI fixed grid pixels containing eddy covariance towers. We demonstrate how to best combine satellite and in-situ datasets and show how ABI attributes useful for ecosystem monitoring vary across space and time. By connecting observation networks that infer rapid changes to the carbon cycle, we can gain a richer understanding of the processes that control it., (© 2024. The Author(s).)

LGBTQ+ women have long been overlooked in sexual and reproductive health research. However, recent research has established that LGBTQ+ women have unique and specific needs that need to be addressed in order to improve effectiveness of sexual health education and practice with this historically and presently underserved population. Informed by a reproductive justice framework coupled with liberation psychology theory, this review discusses the current state of sexual and reproductive health and technologies among LGBTQ+ women. In particular, we focus on a range of HIV prevention and reproductive technologies and their use and promotion, including the internal condom, abortion, oral contraceptives, dapivirine ring, HIV pre-exposure prophylaxis, intrauterine device, and other less studied options, such as the contraceptive sponge. Grounded in an intersectional framing, this review acknowledges the intersecting systems of oppression that affect multiply marginalized women inequitably and disproportionately. A sociohistorical, critical lens is applied to acknowledge the well-documented racist origins of reproductive health technologies and ongoing coercive practices that have led to medical mistrust among marginalized and stigmatized communities, particularly racialized LGBTQ+ women, women with disabilities, and women who are poor or incarcerated. Moreover, we discuss the urgent need to center LGBTQ+ women in research and clinical care, community-engaged health promotion efforts, affirming non-heteronormative sexual health education, and health policies that prioritize autonomy and dismantle structural barriers for this population. We conclude with recommendations and future directions in this area to remedy entrenched disparities in health.

Few studies have sought to untangle the influence of social determinants and pregnancy on adolescent marriage declines. Using longitudinal data from 15- to 17-year-old girls in the Rakai Community Cohort Survey, we assessed how education, socio-economic status, orphanhood and pregnancy contributed to trends in adolescent marriage. We examined descriptive trends and logistic regressions of the associations between social determinants and adolescent marriage, and conducted causal mediation analysis to assess the extent that pregnancy mediated the effect of education on marriage. Between 1999-2018, adolescent marriages and pregnancies dropped substantially (24%-6% and 28%-8%). Girls' secondary schooling was strongly associated with lower marriage risk (aOR marriage=0.09; 95%CI=0.07-0.12), accounting for time. Lower pregnancy rates partially explained the effect of secondary schooling on lower adolescent marriage (aOR indirect effect=0.55; 95%CI=0.421-0.721). Findings affirm the importance of education in preventing adolescent marriages but call attention to the role of pregnancies in influencing adolescent marriages.

Background: One in four Americans report experiencing harassment online via social media and interactive gaming, which includes physical threats, stalking, sexual harassment, and sustained harassment., Objective: The aim of this study was to gain understanding of the state of the science surrounding young adults and sexual violence/harassment harms in virtual reality (VR) as well as possible uses of VR to heal and intervene., Methods: A scoping review was conducted in early 2023 using the Ovid Synthesis Clinical Evidence Manager and the MEDLINE database. Forty-seven articles met inclusion criteria., Results: Our review found a growing body of evidence exploring incidents, effects, possible predictors, and initial strategies to prevent sexual violence in VR and to use the modality to positively intervene. Limited research addresses the effects of harms incurred in VR on (re)traumatization of survivors as well as the development and testing of VR tools used to educate, deliver bystander interventions, transform biases and perceptions via embodiment, and promote healing among survivors., Conclusion: Research addressing sexual violence in VR is needed and should build on the existing peripheral science on gaming and social media environments. Forensic nursing is well positioned to advance strategies of health and safety in VR, just as in the physical world. Incorporating forensic nursing avatars in VR and deploying diverse resources targeted for college-age young adults to prevent harms in VR should be explored safely and ethically. Forensic nurses are also positioned to assess for VR-related harms among patients and to work with private and government sectors to influence regulations and policies., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc.)

Research suggests that health literacy (HL) is critical in preventing and managing health problems. However, over half of adults in Mexico report having inadequate health literacy. Research suggests the parent-child relationship can be a key predictor of developmental competencies; however, little research has examined how dyadic family interactions relate to HL. This study examined whether parent-child relationship conflict was associated with adolescent health literacy among families living in Mexico. Data from a parent-child dyads in Mexico were gathered using online surveys ( N  = 746, 373 parent-child dyads). Our findings suggested that child-reported family conflict-but not parent-reported family conflict - was associated with lower adolescent health literacy. Researchers and practitioners should consider how parent-child conflict may impact adolescent health outcomes, and prioritise child reports in data collection.

Objective . Transcranial magnetic stimulation (TMS) coil design involves a tradeoff among multiple parameters, including magnetic flux density ( B ), inductance ( L ), induced electric ( E ) field, focality, penetration depth, coil heating, etc. Magnetic materials with high permeability have been suggested to enhance coil efficiency. However, the introduction of magnetic core invariably increases coil inductance compared to its air-core counterpart, which in turn weakens the E field. Our lab previously reported a rodent-specific TMS coil with silicon steel magnetic core, achieving 2 mm focality. This study aims to better understand the tradeoffs among B , L, and E in the presence of magnetic core. Approach . The magnetic core initially operates within the linear range, transitioning to the nonlinear range when it begins to saturate at high current levels and reverts to the linear range as coil current approaches zero; both linear and nonlinear analyses were performed. Linear analysis assumes a weak current condition when magnetic core is not saturated; a monophasic TMS circuit was employed for this purpose. Nonlinear analysis assumes a strong current condition with varying degrees of core saturation. Main results . Results reveal that, the secondary E field generated by the silicon steel core substantially changed the dynamics during TMS pulse. Linear and nonlinear analyses revealed that higher inductance coils produced stronger peak E fields and longer E field waveforms. On a macroscopic scale, the effects of these two factors on neuronal activation could be conceptually explained through a one-time-constant linear membrane model. Four coils with different B , L, and E characteristics were designed and constructed. Both E field mapping and experiments on awake rats confirmed that inductance could be much higher than previously anticipated, provided that magnetic material possesses a high saturation threshold. Significance . Our results highlight the novel potentials of magnetic core in TMS coil designs, especially for small animals., (Creative Commons Attribution license.)

Background: Diagnosis and management of neuropathic pain (NP) in foot and ankle patients remain challenging. We investigated the plausibility of using Patient-Reported Outcomes Measurement Information System (PROMIS) Neuropathic Pain Quality (PQ-Neuro) as an initial screening tool to detect NP and track the treatment effects., Methods: Patients with heel pain were prospectively recruited and grouped to no-NP, mild-NP, and severe-NP based on the initial PROMIS PQ-Neuro t scores. Pain Interference (PI), Physical Function (PF), and Self-Efficacy (SE) scores were evaluated at baseline, 30-day, and 90-day follow-up. Other factors such as age, smoking, body mass index (BMI), low back/neck pain, anxiety/depression, and medications were analyzed. Linear mixed modeling was used to assess the main effects of time and NP on PROMIS t scores, comparing minimal clinically important difference (MCID)., Results: Forty-eight patients with mean age of 52.4 years were recruited. Using the PROMIS PQ-Neuro as the assessment tool, 33 patients (69%) were detected to have NP at baseline-23 (48%) mild and 10 (21%) severe. BMI was the only independent factor associated with NP ( P  = .011). Higher baseline PQ-Neuro t score was significantly associated with higher follow-up PQ-Neuro ( P  < .001), PI ( P  = .005), and lower SE ( P  = .04) across time points. Patients with NP showed lower PF at baseline with significantly less improvement in PF (3 vs 9.9, P  = .035) and did not meet MCID., Conclusion: Baseline PROMIS PQ-Neuro ≥46 was significantly associated with worse PI and SE across all time points, with less clinically significant improvements in PF. Prevalence of NP in heel pain patients was high. The PROMIS PQ-Neuro may serve as a valuable tool for detection of NP and guiding clinical treatment decision pathways for heel pain patients., Level of Evidence: Level III, prospective cohort study., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. ICMJE forms for all authors are available online., (© The Author(s) 2023.)

Identifying factors associated with durable viral suppression (DVS) can inform interventions to support young adults living with HIV (YALWH) in sustaining optimal health. We examined associations between client characteristics and DVS among YALWH aged 18-29 who completed an intake assessment and received ≥ 1 Ryan White Part A service in New York City from 1/2017 to 12/2019. Individuals were classified as achieving DVS at least once if they had ≥ 2 suppressed viral load test results ≥ 90 days apart with: (a) no intervening unsuppressed viral load test results in a 12-month period; and (b) no unsuppressed viral load test results after achieving DVS in that 12-month period. Of 2208 YALWH, 92.1% (n = 2034) had sufficient data in the New York City HIV Surveillance Registry to ascertain DVS status. Of these, 68% achieved DVS at least once. Controlling for ART prescription status at intake, YALWH with higher incomes were significantly more likely to achieve DVS at least once. YALWH with lifetime and recent histories of incarceration and/or drug use were significantly less likely to achieve DVS. Our findings underscore the potential role of tailored harm reduction and post-incarceration programs in reducing health inequities among YALWH., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Before the COVID-19 pandemic, nurses had little experience providing care during a pandemic. This project aimed to identify Pearls (suggestions) to survive a pandemic as a nurse., Methods: A phenomenologic design was implemented. Narrative comments were analyzed using Braun & Clarke's Six Phases of Summative Concept Analysis. This paper focuses on responses to a secondary question of this design., Results: One hundred thirty-four professional nurses provided 150 Pearls; of these, 123 Pearls reflected a positive sentiment. The Pearls fit into four themes: take care of yourself and find a balance, work as a team, practice safety, and appreciate that this is a hard time., Conclusion: The COVID-19 pandemic provides a valuable lesson for how nurses can survive future pandemics. Further research is warranted to investigate how useful the Pearls are for nurses in future pandemics and other crises threatening healthcare., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: In the US, despite the recent decline in breast cancer deaths, a persistent mortality disparity exists between black and white women with breast cancer, with black women having a 41% higher death rate. Several studies are now reporting that racial disparities can exist independent of socioeconomic and standard of care issues, suggesting that biological factors may be involved. Caveolin-1 (Cav1) loss in the tumor stromal compartment is a novel clinical biomarker for predicting poor outcome in breast cancer including triple negative subtype, however the mechanism of Cav1 loss is unknown. We previously identified miR-510-5p as a novel oncomir and propose here that the high levels observed in patients is a novel mechanism leading to stromal Cav1 loss and worse outcomes., Methods: Cav1 was identified as a direct target of miR-510-5p through luciferase, western blot and qPCR assays. Stromal cross talk between epithelial cells and fibroblasts was assessed in vitro using transwell co-culture assays and in vivo using xenograft assays., Results: We found that Cav1 is a direct target of miR-510-5p and that expression in fibroblasts results in an 'activated' phenotype. We propose that this could be important in the context of cancer disparities as we also observed increased levels of circulating miR-510-5p and reduced levels of stromal Cav1 in black women compared to white women with breast cancer. Finally, we observed a significant increase in tumor growth when tumor cells were co-injected with miR-510-5p expressing cancer associated fibroblasts in vivo ., Conclusion: We propose that miR-510-5p mediated negative regulation of Cav1 in fibroblasts is a novel mechanism of aggressive tumor growth and may be a driver of breast cancer disparity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 King, Krisanits, Guo, Blake, Nogueira, Jolly, Satterwhite, Turner, Hoffman, Evans-Knowell and Findlay.)

Objectives: To understand public health organizations' experiences providing comprehensive COVID-19 case investigation and contact tracing, and related promising practices with refugee, immigrant and migrant communities., Methods: We interviewed public health professionals (September 2020 to February 2021) from local and state health departments using a geographically stratified, purposive sampling approach. A multidisciplinary team at the National Resource Center for Refugees, Immigrants and Migrants (NRC-RIM) conducted a thematic analysis of the data., Results: Six themes were identified: understanding community and public health context, cultivating relationships, ensuring linguistic and cultural concordance, communicating intentionally, evolving response, and implementing equity. The interconnection of themes and promising practices is explored., Conclusion: As public health continues to learn from and build upon COVID-19 response experiences, the thematic findings and potential promising practices identified in this project may foster proactive, community-engaged solutions for public health, and other organizations working and partnering with refugee, immigrant, and migrant communities. Implementing these findings with COVID-19 into current and future public health crisis responses may improve public health, collaborations with refugee, immigrant, and migrant communities, and staff wellbeing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dawson-Hahn, Fredkove, Karim, Mohamed, Abudiab, de Acosta, Ebengho, Garcia, Hoffman, Keaveney, Mann, Thomas, Yu and Yun.)

Carbapenem-resistant Enterobacterales (CRE) are among the most concerning antibiotic resistance threats due to high rates of multidrug resistance, transmissibility in health care settings, and high mortality rates. We evaluated the potential for regional genomic surveillance to track the spread of bla -carrying CRE (KPC-CRE) by using isolate collections from health care facilities in three U.S. states. Clinical isolates were collected from Connecticut (2017 to 2018), Minnesota (2012 to 2018), and Tennessee (2016 to 2017) through the U.S. Centers for Disease Control and Prevention's Multi-site Gram-negative Surveillance Initiative (MuGSI) and additional surveillance. KPC-CRE isolates were whole-genome sequenced, yielding 255 isolates from 214 patients across 96 facilities. Case report data on patient comorbidities, facility exposures, and interfacility patient transfer were extracted. We observed that in Connecticut, most KPC-CRE isolates showed evidence of importation from outside the state, with limited local transmission. In Minnesota, cases were mainly from sporadic importation and transmission of KPC -carrying CRE (KPC-CRE) by using isolate collections from health care facilities in three U.S. states. Clinical isolates were collected from Connecticut (2017 to 2018), Minnesota (2012 to 2018), and Tennessee (2016 to 2017) through the U.S. Centers for Disease Control and Prevention's Multi-site Gram-negative Surveillance Initiative (MuGSI) and additional surveillance. KPC-CRE isolates were whole-genome sequenced, yielding 255 isolates from 214 patients across 96 facilities. Case report data on patient comorbidities, facility exposures, and interfacility patient transfer were extracted. We observed that in Connecticut, most KPC-CRE isolates showed evidence of importation from outside the state, with limited local transmission. In Minnesota, cases were mainly from sporadic importation and transmission of bla KPC -carrying Klebsiella pneumoniae ST258, and clonal expansion of bla KPC -carrying Enterobacter hormaechei ST171, primarily at a single focal facility and its satellite facilities. In Tennessee, we observed transmission of diverse strains of bla KPC -carrying Enterobacter and Klesbiella , with evidence that most derived from the local acquisition of bla KPC plasmids circulating in an interconnected regional health care network. Thus, the underlying processes driving KPC-CRE burden can differ substantially across regions and can be discerned through regional genomic surveillance. This study provides proof of concept that integrating genomic data with information on interfacility patient transfers can provide insights into locations and drivers of regional KPC-CRE burden that can enable targeted interventions., Competing Interests: The authors declare no conflict of interest.

Introduction: The purpose of our study is to analyze the outcomes of traumatic posterolateral elbow dislocations using patient-reported outcomes measurement information system (PROMIS). We hypothesized that physical function (PF) and upper extremity (UE) scores in PROMIS will significantly improve over six months of follow-up and correlate with a positive change in the patient-acceptable symptom state (PASS)., Methods: This is a seven-year retrospective study of 165 consecutive adult patients with traumatic posterolateral elbow dislocations. Demographic information, PROMIS PF, PROMIS UE, PROMIS pain interference (PI), PROMIS depression, and PASS were recorded over six months of follow-up., Results: At the time of injury, mean PROMIS scores were PF 41.24 (SD 11.16), UE 34.27 (SD 11.87), PI 60.44 (SD 8.07), and depression 49.82 (SD 10.42). At six months, the mean PROMIS scores were PF 39.71 (SD 9.71), UE 33.95 (SD 9.09), PI 57.35 (SD 8.59), and depression 51.43 (SD 10.62). The overall six-month changes in PROMIS scores were PF -1.53, UE -0.32, PI -3.09, and depression +1.61. At the 6-month follow-up, 41.7% responded positively on the PASS, which correlated only with PROMIS PI., Conclusions: Among patients who improved from negative to positive response on PASS, the PROMIS PF, UE, and depression scores did not significantly improve. Only PROMIS PI correlated with PASS at the six-month follow-up; PROMIS PI significantly improved among simple posterolateral elbow dislocation patients at both short-term and long-term follow-up points. PROMIS PF, UE, and depression did not significantly differ between time of injury and short-term and long-term follow-up points., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Carroll et al.)

Traumatic Brain Injury (TBI) is a risk factor for Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD) and otherwise classified post-traumatic neurodegeneration (PTND). Targeted research is needed to elucidate the circumstances and mechanisms through which TBI contributes to the initiation, development, and progression of AD/ADRD pathologies including multiple etiology dementia (MED). The National Institutes of Health hosts triennial ADRD summits to inform a national research agenda, and TBI was included for a second time in 2022. A multidisciplinary expert panel of TBI and dementia researchers was convened to re-evaluate the 2019 research recommendations for understanding TBI as an AD/ADRD risk factor and to assess current progress and research gaps in understanding post-TBI AD/ADRD. Refined and new recommendations were presented during the MED special topic session at the virtual ADRD Summit in March 2022. Final research recommendations incorporating broad stakeholder input are organized into four priority areas as follows: (1) Promote interdisciplinary collaboration and data harmonization to accelerate progress of rigorous, clinically meaningful research; (2) Characterize clinical and biological phenotypes of PTND associated with varied lifetime TBI histories in diverse populations to validate multimodal biomarkers; (3) Establish and enrich infrastructure to support multimodal longitudinal studies of individuals with varied TBI exposure histories and standardized methods including common data elements (CDEs) for ante-mortem and post-mortem clinical and neuropathological characterization; and (4) Support basic and translational research to elucidate mechanistic pathways, development, progression, and clinical manifestations of post-TBI AD/ADRDs. Recommendations conceptualize TBI as a contributor to MED and emphasize the unique opportunity to study AD/ADRD following known exposure, to inform disease mechanisms and treatment targets for shared common AD/ADRD pathways.

Purpose: The purpose of our study was to compare the 1-year revision surgery rates and outcomes of open versus endoscopic carpal tunnel release. Our hypothesis was that, compared to open release, endoscopic carpal tunnel release was an independent risk factor for revision surgery within 1-year., Methods: This was a retrospective cohort study of 4338 patients undergoing isolated endoscopic or open carpal tunnel release. Demographic data, medical comorbidities, surgical approach, need for revision surgery, hand dominance, history of prior injection, and Patient Reported Outcomes Measurement Information System upper extremity (UE), pain interference (PI) and physical function scores were analyzed. Multivariable analysis was used to identify the risk factors for revision surgery within one year of the index procedure., Results: In total, 3280 patients (76%) underwent open and 1058 (24%) underwent endoscopic carpal tunnel release. Within one year of the index procedure, 45 patients required revision carpal tunnel release. The average time to revision was 143 days. The rate of revision carpal tunnel release in the open group was 0.71% compared to 2.08% in the endoscopic group. Multivariable analysis demonstrated that endoscopic surgery, male sex, cubital tunnel syndrome, tobacco use, and diabetes were associated independently with revision surgery., Conclusions: In this study, we found that endoscopic carpal tunnel release was associated independently with a 2.96 times greater likelihood of requiring revision carpal tunnel release within one year, compared to open carpal tunnel release. Male sex, concurrent cubital tunnel syndrome, tobacco use, and diabetes also were associated independently with greater risk of needing revision carpal tunnel release within one year., Type of Study/level of Evidence: Prognostic II., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: To characterize the experience of providing nursing care amid the COVID-19 pandemic., Methods: A qualitative, phenomenology method was used. Data were collected via a confidential electronic survey., Results: A total of 166 nurses completed the survey, of which 63 (37.9%) took care of a patient with COVID-19. Four themes (with subthemes) emerged from the survey data: It feels like a marathon that won't end; Take care of yourself or you cannot take care of anyone else effectively; I'm a nurse so I can take care of sick patients, however, it is harder to go to work now; and It is challenging not to be angry., Conclusion: Nurses remain proud of their role as a nurse. However, the joy related to work faded as nurses fought against being angry with patients, visitors, and other clinicians who did not follow safety precautions, such as wearing masks, and social distancing. The perception of running a marathon illustrates the exhaustion nurses are experiencing., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Since rapid population growth challenges longitudinal population-based HIV cohorts in Africa to maintain coverage of their target populations, this study evaluated whether the exclusion of some residents due to growing population size biases key HIV metrics like prevalence and population-level viremia., Design, Setting and Participants: Data were obtained from the Rakai Community Cohort Study (RCCS) in south central Uganda, an open population-based cohort which began excluding some residents of newly constructed household structures within its surveillance boundaries in 2008. The study includes adults aged 15-49 years who were censused from 2019 to 2020., Measures: We fit ensemble machine learning models to RCCS census and survey data to predict HIV seroprevalence and viremia (prevalence of those with viral load >1000 copies/mL) in the excluded population and evaluated whether their inclusion would change overall estimates., Results: Of the 24 729 census-eligible residents, 2920 (12%) residents were excluded from the RCCS because they were living in new households. The predicted seroprevalence for these excluded residents was 10.8% (95% CI: 9.6% to 11.8%)-somewhat lower than 11.7% (95% CI: 11.2% to 12.3%) in the observed sample. Predicted seroprevalence for younger excluded residents aged 15-24 years was 4.9% (95% CI: 3.6% to 6.1%)-significantly higher than that in the observed sample for the same age group (2.6% (95% CI: 2.2% to 3.1%)), while predicted seroprevalence for older excluded residents aged 25-49 years was 15.0% (95% CI: 13.3% to 16.4%)-significantly lower than their counterparts in the observed sample (17.2% (95% CI: 16.4% to 18.1%)). Over all ages, the predicted prevalence of viremia in excluded residents (3.7% (95% CI: 3.0% to 4.5%)) was significantly higher than that in the observed sample (1.7% (95% CI: 1.5% to 1.9%)), resulting in a higher overall population-level viremia estimate of 2.1% (95% CI: 1.8% to 2.4%)., Conclusions: Exclusion of residents in new households may modestly bias HIV viremia estimates and some age-specific seroprevalence estimates in the RCCS. Overall, HIV seroprevalence estimates were not significantly affected., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Acute kidney injury (AKI) is characterized by cell death and inflammation. CD24 is a protein induced during tissue damage and is not expressed in mature renal tissue. We explored the role of CD24 in the pathogenesis of folic acid-induced AKI (FA-AKI) in mice. A single Intraperitoneal (IP) injection of folic acid induced AKI in WT and CD24 -/- mice. Renal function tests, histological analysis, immunohistochemistry, Western blot analysis, and ELISA were performed to assess the severity of renal damage and the intensity of the inflammatory response. FA-AKI induced CD24 in the distal tubular epithelial cells. Compared to WT mice, FA-AKI CD24 -/- mice exhibited an attenuated reduction in renal function and histological injury, lower serum IL-10 and interferon γ, and decreased expression of renal TNFα. In contrast, renal and systemic IL-33 upregulation were augmented. CD24 -/- FA-AKI animals exhibited increased splenic margination and renal infiltration of regulatory T cells (Tregs). At day 7, FA-AKI CD24 -/- mice exhibited increased expression of tubular pro-apoptotic and decreased anti-apoptotic proteins compared to WT animals. Anti-CD24 antibody administration to FA-AKI mice attenuated the decrease in renal function as well as the histological injury. Renal biopsies from patients with ATN stained strongly for CD24 in the distal tubules. In conclusion, during AKI, upregulation of CD24 promotes renal inflammation through inhibition of Treg infiltration and diversion of cell death towards necrosis rather than apoptosis. Neutralization of CD24 may prove a target for future therapies in AKI.

Objectives: To assess the cognitive capacity of early, middle, and late adolescents and their parents or guardians to provide informed consent to a population-based cohort study., Study Design: Adolescent-parent/guardian dyads including 40 early (n = 80; 10-14 years), 20 middle (15-17 years), and 20 late (18-19 years) adolescents were recruited from the Rakai Community Cohort Study, an open demographic cohort in Uganda. Participants were administered the MacArthur Competence Assessment Tool for Clinical Research, a structured open-ended assessment; interviews were recorded and transcribed. Twenty transcripts were scored independently by two coders; the intraclass correlation coefficient was 0.89. The remaining interviews were scored individually. We compared mean scores for early and middle/late adolescents using a one-sided t test and score differences between parent/guardian and adolescent dyads using two-sided paired t tests., Results: Early adolescents (mean score, 28.8; 95% CI, 27.1-30.5) scored significantly lower (P < .01) than middle/late adolescents (32.4; 31.6-33.1). In paired dyad comparisons, we observed no statistically significant difference in scores between parents/guardians and middle/late adolescents (difference, -0.2; 95% CI, -1.0-0.6). We found a statistically significant difference in scores between parents/guardians and early adolescents (difference, 3.0; 95% CI, 1.2-4.8)., Conclusions: The capacity of adolescents-of different ages and in diverse settings-to comprehend risks, benefits, and other elements of informed consent is a critical but understudied area in research ethics. Our findings support the practice of having middle and late adolescents provide independent informed consent for sexual and reproductive health studies. Early adolescents may benefit from supported decision-making approaches., (Copyright © 2022. Published by Elsevier Inc.)