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Background: We estimate the prevalence of drug injection, the variables associated with having ever injected and the proportion of ever injectors whose first drug injection was for having sex; we describe the first drug injection episode, analyze the drugs most frequently injected and estimate the prevalence of risky injecting behaviors. Methods: The participants were 3387 MSM without a previous HIV diagnosis attending four HIV/STI diagnosis services in Madrid and Barcelona. Lifetime prevalence and prevalence ratios (PRs) by different factors were calculated using Poisson regression models with robust variance. We compared the characteristics of first drug injection episode, lifetime injection and risky injecting behaviors of those whose first injection was for sex (FIS) with those whose was not (non-FIS). Results: Lifetime prevalence of injection was 2.1% (CI 1.7–2.7). In the multivariate analysis, it was strongly associated with having been penetrated by more than five men in the last 12 months (aPR = 10.4; CI 2.5–43.4) and having met most of their partners at private parties (aPR = 7.5; CI 4.5–12.3), and less strongly with other factors. Of those who had ever injected drugs, 81.9% injected for sex the first time they injected drugs (FIS). At first injection, FIS participants had a mean age of 31 years, 62.7% used mephedrone and 32.2% methamphetamine on that occasion. Of this FIS group 39.0% had ever shared drugs or equipment and 82.6% had always shared for sex. Some 30.8% of non-FIS reported having also injected drugs for sex later on. Conclusions: Only two out of a hundred had ever injected, most to have sex and with frequent drug or injecting equipment sharing. Injecting for sex is the most common first episode of drug injection and is the most efficient risky behavior for the transmission of HIV, hepatitis B or C and other blood-borne infections. MSM participating in private parties should be considered a priority group for prevention policies. [ABSTRACT FROM AUTHOR]

Background: This article describes the rationale and design of a population-based survey of dementia in Valladolid northwestern Spain). The main aim of the study was to assess the epidemiology of dementia and its subtypes. Prevalence of anosognosia in dementia patients, nutritional status, diet characteristics, and determinants of non-diagnosed dementia in the community were studied. The main socio demographic, educational, and general health status characteristics of the study population are described. Methods: Cross-over and cohort, population-based study. A two-phase door-to-door study was performed. Both urban and rural environments were included. In phase 1 (February 2009 - February 2010) 28 trained physicians examined a population of 2,989 subjects (age: ≥ 65 years). The seven-minute screen neurocognitive battery was used. In phase 2 (May 2009 - May 2010) 4 neurologists, 1 geriatrician, and 3 neuropsychologists confirmed the diagnosis of dementia and subtype in patients screened positive by a structured neurological evaluation. Specific instruments to assess anosognosia, the nutritional status and diet characteristics were used. Of the initial sample,2,170 subjects were evaluated (57% female, mean age 76.5 ± 7.8, 5.2% institutionalized), whose characteristics are described. 227 persons were excluded for various reasons. Among those eligible were 592 non-responders. The attrition bias of non-responders was lower in rural areas. 241 screened positive (11.1%).Discussion: The survey will explore some clinical, social and health related life-style variables of dementia. The population size and the diversification of social and educational backgrounds will contribute to a better knowledge of dementia in our environment. [ABSTRACT FROM AUTHOR]

Background: Data are limited regarding use of narrow-spectrum agents for the treatment of complicated urinary tract infections (cUTIs). We sought to evaluate cefazolin compared with ceftriaxone for the empiric treatment of patients with cUTIs in an inpatient setting., Methods: We conducted a retrospective, single-center, cohort study involving patients with cUTI treated with cefazolin or ceftriaxone at a Veterans Affairs (VA) medical center between November 1, 2019 and September 30, 2022. The primary outcome was 30-day clinical success, defined as resolution of signs and symptoms of infection without re-initiation of antibiotics during hospitalization or relapse within 30 days after cUTI diagnosis. Secondary outcomes included hospital length of stay and Clostridioides difficile infection (CDI) within 30 days of the end of antibiotic therapy., Results: We identified 113 patients with cUTI treated with cefazolin (n = 52) or ceftriaxone (n = 61) meeting study criteria. The study arms had similar demographics, although patients treated with ceftriaxone more frequently had subjective fever on admission or nephrolithiasis while cefazolin-treated patients had more altered mental status as the only UTI symptom reported, urinary catheter, and had a single dose of another antibiotic prior to starting the study medication. Clinical success was achieved in 47/52 (90%) and 53/61 (87%) in the cefazolin and ceftriaxone groups, respectively (P = 0.56). Additionally, there were no statistically significant differences in length of stay and development of CDI., Conclusions: In this retrospective cohort study of patients with cUTI at a VA medical center, empiric therapy with cefazolin appears to be a safe and effective treatment option., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved under non-regulated research as a quality improvement project; therefore was exempt from informed consent, ethics committee, or Institutional Review Board approval, as determined by the University of Texas Health at San Antonio Institutional Review Board (San Antonio, TX, USA). This study was a retrospective chart review of an intervention that had already been made under the local antimicrobial stewardship program as quality improvement. All methods were performed in accordance with the institution relevant guidelines and regulations. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Over 20 years has passed since the principles of gender-responsive correctional strategies were published in a foundational report in the U.S. These practices acknowledge the unique characteristics and life experiences of justice-involved women, have undergone rigorous empirical testing, and are shown to effectively reduce women's recidivism. In part, they supported the United Nation's adoption of minimum human rights afforded to women serving custodial and non-custodial criminal sentences. This paper presents updated research evidence that continues to amplify the need for gender-responsive principles and practices, including the role of victimization in girls' and women's offending trajectories and the intersection of relationships, relational identity, and trauma as key drivers for justice involvement. Further, because the perinatal needs of justice-involved women are a frequently overlooked area of inquiry among the gender-responsive literature, this scholarship is also summarized using a reproductive justice framework. Finally, we illustrate the impact of gender-responsive scholarship by sharing some of the practice and technology innovations that have emerged, while acknowledging there is much yet to accomplish., Competing Interests: Declarations. Ethics approval and consent to participate: There were no participants in the research and therefore IRB approval and consent to participate were not necessary. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Point-of-care ultrasound (POCUS) use has become ubiquitous in the field of anesthesiology. However, POCUS training curriculum in anesthesiology residencies vary widely. We performed a survey study to better understand the structure of existing POCUS training and identify barriers to instituting a POCUS curriculum for anesthesiology trainees., Competing Interests: Declarations. Ethics approval and consent to participate: Non-regulated research, exempt from IRB approval (Protocol: 20220222EX). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Trastuzumab, a monoclonal antibody against human epidermal growth factor receptor 2 (HER2), is often the first line treatment for HER2 positive breast cancer. Although trastuzumab is effective, it has cardiotoxic effects and therefore requires cardiotoxicity monitoring via serial transthoracic echocardiograms (TTEs). We aimed to evaluate risk factors for trastuzumab related cardiac dysfunction in a South Texas population that is uniquely a majority Hispanic population., Methods: A retrospective study was conducted of female patients with HER2-positive breast cancer who received trastuzumab treatment from 2015 to 2021. A total of 180 patients were identified. Patients without a baseline TTE and a baseline left ventricle ejection fraction (LVEF) less than 53% were excluded. The final sample size included 132 patients. Cardiac dysfunction was defined as a drop in LVEF by more than 10% to less than 53% during the 1-year study period., Results: The incidence of cardiac dysfunction was 6% in the study population. Hispanic/Latino patients composed 58% of the study population and represented 50% of patients who experienced cardiotoxicity. Of the patients who developed cardiotoxicity, 50% had hypertension, 25% had hyperlipidemia, 12.5% had type 2 diabetes mellitus, and 12.5% had previous coronary artery bypass grafts. A total of 12.5% had a history of radiation, 25% had a history of anthracycline therapy, 37.5% were former smokers, and 25% were former alcohol users., Conclusions: The incidence of trastuzumab-related cardiotoxicity in this Hispanic/Latino majority-minority population was 6%, which is surprisingly lower than the 9% cardiotoxicity rate observed in a predominantly white population in a previous study by Otchere et al., in 2023. Further studies are needed to determine the factors contributing to the reduced cardiotoxicity rate observed in this Hispanic population., Competing Interests: Declarations. Consent to participate: The study was exempt from consent requirement due it being a quality improvement project. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Gestational trophoblastic neoplasms consist of complete and partial hydatidiform moles, both of which are considered aberrant conceptuses. Both conditions, complete hydatidiform mole (CHM) and partial hydatidiform mole (PHM), differ in histological characteristics, genetic origin and content and clinical features. CHM have a diploid karyotype, mostly 46,XX but lack maternal genetic contribution with all chromosomes of paternal origin. High-resolution SNP microarray testing is an efficient method used to determine the parental contribution of the genomic material in molar pregnancies and confirm the diagnosis., Case Presentation: We present a case of CHM in a 43-year-old, G3P2Ab1 who presented to the emergency department with 2 episodes of heavy bleeding. Chromosome analysis showed a normal 46,XX karyotype but with a homozygous pericentric inversion on chromosome 9. High-resolution SNP microarray studies detected whole genome uniparental isodisomy., Conclusion: We present a case of CHM with homozygous pericentric inversion on chromosome 9 and whole genome uniparental isodisomy. This case illustrates the efficacy of high-resolution SNP microarray in confirming the diagnosis of CHM., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable since this is a case report and no patient identifiers are used. This study protocol was reviewed and the need for approval was waived by the Institutional Review Board (IRB) since this was determined to be not human research. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: The immature lungs of very preterm infants are exposed to supraphysiologic oxygen, contributing to bronchopulmonary dysplasia (BPD), a chronic lung disease that is the most common morbidity of prematurity. While the microbiota significantly influences neonatal health, the relationship between the intestinal microbiome, particularly micro-eukaryotic members such as fungi and yeast, and lung injury severity in newborns remains unknown., Results: Here, we show that the fungal microbiota modulates hyperoxia-induced lung injury severity in very low birth weight premature infants and preclinical pseudohumanized and altered fungal colonization mouse models. Instead of fungal communities dominated by Candida and Saccharomyces, the first stool microbiomes of infants who developed BPD had less interconnected community architectures with a greater diversity of rarer fungi. After using a pseudohumanized model to show that transfer to the neonatal microbiome from infants with BPD increased the severity of lung injury, we used gain and loss of function approaches to demonstrate that modulating the extent of initial neonatal fungal colonization affected the extent of BPD-like lung injury in mice. We also identified alterations in the murine intestinal microbiome and transcriptome associated with augmented lung injury., Conclusions: These findings demonstrate that features of the initial intestinal fungal microbiome are associated with the later development of BPD in premature neonates and exert a microbiome-driven effect that is transferable and modifiable in murine models, which suggests both causality and a potential therapeutic strategy. Video Abstract., Competing Interests: Declarations. Ethics approval and consent to participate: The human study protocol was approved by the Institutional Review Board of The University of Tennessee under protocol 17–05311-XP and conducted in accordance with the Declaration of Helsinki. The human cohort for FMT samples was approved under protocol IRB-300003994 by the IRB at the University of Alabama at Birmingham (UAB, Birmingham, AL, USA). Mouse experiments were performed at UAB under IACUC protocol 22042. Consent for publication: Assent for publication was obtained from the mother during study enrollment. Competing interests: CL is the founder of ResBiotic Nutrition, Inc. and Alveolus Bio, Inc., from which he reports salary and stock options, and TN is now an employee, thereof. KW and NA are scientific advisors to these companies and report consulting fees and stock options from the same. The remaining authors report no disclosures., (© 2025. The Author(s).)

Alzheimer's disease (AD) is among the most devastating neurodegenerative disorders with limited treatment options. Emerging evidence points to the involvement of lipid dysregulation in the development of AD. Nevertheless, the precise lipidomic landscape and the mechanistic roles of lipids in disease pathology remain poorly understood. This review aims to highlight the significance of lipidomics and lipid-targeting approaches in the diagnosis and treatment of AD. We summarized the connection between lipid dysregulation in the human brain and AD at both genetic and lipid species levels. We briefly introduced lipidomics technologies and discussed potential challenges and areas of future advancements in the lipidomics field for AD research. To elucidate the central role of lipids in converging multiple pathological aspects of AD, we reviewed the current knowledge on the interplay between lipids and major AD features, including amyloid beta, tau, and neuroinflammation. Finally, we assessed the progresses and obstacles in lipid-based therapeutics and proposed potential strategies for leveraging lipidomics in the treatment of AD., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: All authors have reached consent for publication. Conflict of interest: The authors declare no conflict of interest., (© 2025. The Author(s).)

Immunotherapy has transformed the landscape of cancer treatment, with chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy emerging as a front runner in addressing some hematological malignancies. Despite its considerable efficacy, the occurrence of severe adverse effects associated with CAR-T cell therapy has limited their scope and prompted the exploration of alternative therapeutic strategies. Natural killer (NK) cells, characterized by both their innate cytotoxicity and ability to lyse target cells without the constraint of peptide specificity conferred by a major histocompatibility complex (MHC), have similarly garnered attention as a viable immunotherapy. As such, another therapeutic approach has recently emerged that seeks to combine the continued success of CAR-T cell therapy with the flexibility of NK cells. Clinical trials involving CAR-engineered NK (CAR-NK) cell therapy have exhibited promising efficacy with fewer deleterious side effects. This review aims to provide a concise overview of the cellular and molecular basis of NK cell biology, facilitating a better understanding of advancements in CAR design and manufacturing. The focus is on current approaches and strategies employed in CAR-NK cell development, exploring at both preclinical and clinical settings. We will reflect upon the achievements, advantages, and challenges intrinsic to CAR-NK cell therapy. Anticipating the maturation of CAR-NK cell therapy technology, we foresee its encouraging prospects for a broader range of cancer patients and other conditions. It is our belief that this CAR-NK progress will bring us closer to making significant strides in the treatment of refractory and recurrent cancers, as well as other immune-mediated disorders., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: None of the authors of this manuscript report any competing interests.

Background: Inequity in asthma and COVID-19 outcomes and research among Hispanic or Latino individuals is well established. Patient centered outcomes research (PCOR) may help address these inequalities. This report describes the development, implementation, and evaluation of a virtual conference series program titled "Unidos Hablemos de/United, Let's Talk About" intended to address the health literacy of the Hispanic/Latino community regarding asthma and COVID-19 and to encourage involvement in PCOR., Methods: A Project Advisory Group consisting of Hispanic/Latino patient advisors who had been diagnosed with asthma and/or COVID-19, healthcare providers, researchers, a Hispanic faith-based leader, and a program evaluator designed and implemented a six-month series of monthly one-hour virtual sessions. Speakers and topics were selected that fit the Hispanic/Latino community and culture regarding asthma, COVID-19, and PCOR. Recruitment was through a multichannel digital promotion strategy, including social media. The virtual sessions were free on the ZOOM webinar platform and included interactive polling questions, live chat box, and Q&A. All audio and written materials from the sessions were translated into Spanish and English. Evaluations were used to rate the overall satisfaction with the program., Results: An average of 382 participants attended each of the six sessions, and participation generally increased with each session. The proportion of participants who considered themselves a Hispanic/Latino patient with asthma, caregiver, or clergy who served Hispanic/Latino communities increased by 100% from session one to session two. Preference for materials in Spanish ranged from 12 to 20% of participants over the six sessions. Among the sessions, 74-84% of polling question respondents indicated they would be willing to participate in research or a study, and 88% said they would be willing to serve as a patient partner/advocate. Program evaluations consistently indicated high satisfaction with the session content, session format, and feeling of inclusion., Conclusions: Unidos Hablemos provided a voice to the Hispanic/Latino community that will inform future strategies to improve equity in asthma management, COVID-19, and PCOR. Patient speakers generated trust from the participants and "bridged the gap" between physicians, researchers, and the Hispanic/Latino community. Providing evidence-based, current information will empower patients and caregivers to make informed healthcare decisions., Competing Interests: Declarations Ethics approval and consent to participate An Institutional Review Board granted the program as exempt from human subject research oversight. Consent for publication Not applicable. Competing interests V. Hernandez-Trujillo has received grant support from the Immune Deficiency Foundation, has served as a consultant for Kaleo, Pharming, National Peanut Board, and the Allergy & Asthma Network, has participated in webinars and podcasts for the American College of Allergy, Asthma and Immunology, has been on speakers bureaus for Takeda and CSL, has participated in advisory boards for Takeda, Bayer, Aimmune, Enzyvant, Pfizer, Regeneron, Sanofi/Genzyme, ARS, Bryn, Kaleo and Genentech, and has received honoraria from Amgen for participation in a panel. R. Marie Ramos, A. Colon Moya, D. Delarosa, and M. Lorenzi have nothing to disclose. M. Gieminiani, M. Hart, L. Mitchell, and D.D. Gardner have nothing to disclose, however, their employer Allergy & Asthma Network has received funding from Sanofi Regeneron, Genentech, Pfizer, and Novartis for unbranded disease awareness and education., (© 2024. The Author(s).)

Background: Aside from the canonical role of PDL1 as a tumour surface-expressed immune checkpoint molecule, tumour-intrinsic PDL1 signals regulate non-canonical immunopathological pathways mediating treatment resistance whose significance, mechanisms, and therapeutic targeting remain incompletely understood. Recent reports implicate tumour-intrinsic PDL1 signals in the DNA damage response (DDR), including promoting homologous recombination DNA damage repair and mRNA stability of DDR proteins, but many mechanistic details remain undefined., Methods: We genetically depleted PDL1 from transplantable mouse and human cancer cell lines to understand consequences of tumour-intrinsic PDL1 signals in the DNA damage response. We complemented this work with studies of primary human tumours and inducible mouse tumours. We developed novel approaches to show tumour-intrinsic PDL1 signals in specific subcellular locations. We pharmacologically depleted tumour PDL1 in vivo in mouse models with repurposed FDA-approved drugs for proof-of-concept clinical translation studies., Results: We show that tumour-intrinsic PDL1 promotes the checkpoint kinase-2 (Chk2)-mediated DNA damage response. Intracellular but not surface-expressed PDL1 controlled Chk2 protein content post-translationally and independently of PD1 by antagonising PIRH2 E3 ligase-mediated Chk2 polyubiquitination and protein degradation. Genetic tumour PDL1 depletion specifically reduced tumour Chk2 content but not ATM, ATR, or Chk1 DDR proteins, enhanced Chk1 inhibitor (Chk1i) synthetic lethality in vitro in diverse human and murine tumour models, and improved Chk1i efficacy in vivo. Pharmacologic tumour PDL1 depletion with cefepime or ceftazidime replicated genetic tumour PDL1 depletion by reducing tumour Chk2, inducing Chk1i synthetic lethality in a tumour PDL1-dependent manner, and reducing in vivo tumour growth when combined with Chk1i., Conclusions: Our data challenge the prevailing surface PDL1 paradigm, elucidate important and previously unappreciated roles for tumour-intrinsic PDL1 in regulating the ATM/Chk2 DNA damage response axis and E3 ligase-mediated protein degradation, suggest tumour PDL1 as a biomarker for Chk1i efficacy, and support the rapid clinical potential of pharmacologic tumour PDL1 depletion to treat selected cancers., (© 2024. The Author(s).)

The Greater Fifth Ward (GFW) is a Northeast Houston, Texas, neighborhood with a legacy of industrial contamination and a confirmed cancer cluster. To understand self-rated health in the GFW, community-based participatory research (CBPR), was used to promote the inclusion of all partners. CBPR involves the community during each stage of the research process from design to research dissemination. A complete census was conducted, and 114 surveys were obtained in the environmental justice (EJ) community from July to November 2021. EJ communities shoulder an unfair burden of environmental exposures, pollution, and poor built environments. Mental and physical health were measured using the validated 12-item Short Form Health Survey (SF-12v2). We posited that the Black or African American (Black/AA) community would have lower mental composite scores (MCS) and physical composite scores (PCS) compared to the nation and their White counterparts. The MCS and PCS were calculated and compared against the national mean. Overall, participants had higher MCS and lower PCS than the national mean. Black/AA males and females had lower MCS compared to their White counterparts. White females had the lowest PCS among all respondents, significantly lower than the national average. MCS was lower among those who lived in the neighborhood longer. Burdens from pollution may impact residents' health and perceived health. Targeted interventions or programs that improve mental or physical health would benefit this community and other inequitably burdened neighborhoods., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

APOE is a major genetic factor in late-onset Alzheimer's disease (LOAD), with APOE4 increasing risk, APOE3 acting as neutral, and APOE2 offering protection. APOE also plays key role in lipid metabolism, affecting both peripheral and central systems, particularly in lipoprotein metabolism in triglyceride and cholesterol regulation. APOE2 is linked to Hyperlipoproteinemia type III (HLP), characterized by mixed hypercholesterolemia and hypertriglyceridemia due to impaired binding to Low-Density Lipoproteins receptors. To explore the impact of human APOE isoforms on LOAD and lipid metabolism, we developed Long-Evans rats with human APOE2, APOE3, or APOE4 in place of rat Apoe. These rats were crossed with those carrying a humanized App allele to express human Aβ, which is more aggregation-prone than rodent Aβ, enabling the study of human APOE-human Aβ interactions. In this study, we focused on 80-day-old adolescent rats to analyze early changes that may be associated with the later development of LOAD. We found that APOE2 hAβ rats had the highest levels of APOE in serum and brain, with no significant transcriptional differences among isoforms, suggesting variations in protein translation or stability. Aβ43 levels were significantly higher in male APOE4 hAβ rats compared to APOE2 hAβ rats. However, no differences in Tau or phosphorylated Tau levels were observed across the APOE isoforms. Neuroinflammation analysis revealed lower levels of IL13, IL4 and IL5 in APOE2 hAβ  males compared to APOE4 hAβ males. Neuronal transmission and plasticity tests using field Input-Output (I/O) and long-term potentiation (LTP) recordings showed increased excitability in all APOE-carrying rats, with LTP deficits in APOE2 hAβ and APOE4 hAβ rats compared to Apoe hAβ and APOE3 hAβ rats. Additionally, a lipidomic analysis of 222 lipid molecular species in serum samples showed that APOE2 hAβ  rats displayed elevated triglycerides and cholesterol, making them a valuable model for studying HLP. These rats also exhibited elevated levels of phosphatidylglycerol, phosphatidylserine, phosphatidylethanolamine, sphingomyelin, and lysophosphatidylcholine. Minimal differences in lipid profiles between APOE3 hAβ and APOE4 hAβ rats reflect findings from mouse models. Future studies will include comprehensive lipidomic analyses in various CNS regions and at older ages to further validate these models and explore the effects of APOE isoforms on lipid metabolism in relation to AD pathology., (© 2024. The Author(s).)

Background: Neighborhood factors of social isolation have been understudied, hindering efforts to reduce social isolation at the neighborhood level. This study aims to investigate the longitudinal effects of neighborhood social cohesion and physical disorder on social isolation in community-dwelling older adults, as well as to examine whether race/ethnicity moderates the neighborhood-isolation relationship., Methods: We used 11-year data from the National Health and Aging Trend Study, a longitudinal national study of Medicare beneficiaries aged 65 and older. Social isolation was measured through a summary score across four domains: marital/partner status, family and friend contact, religious attendance, and club participation. A series of weighted mixed-effects logistic regression models were performed to test the study aims. Sample sizes ranged from 7,303 to 7,291 across individual domains of social isolation., Results: Approximately 20% of participants reported social isolation. Findings indicated a negative association between neighborhood social cohesion and social isolation. Higher levels of neighborhood social cohesion were longitudinally associated with lower odds of social isolation (odds ratio [OR] = 0.52, 95% CI: 0.47-0.58). Yet, the presence of neighborhood physical disorder was associated with an increased risk of overall social isolation ([OR] = 1.2, 95% CI: 1.00, 1.44). Race/ethnicity significantly moderated the effects of neighborhood social cohesion and physical disorder on social isolation. The odds of no in-person visits associated with neighborhood social cohesion are smaller among Black adults compared to White adults. Black adults had constantly lower odds of isolation from religious attendance compared to White adults regardless of the level of neighborhood social cohesion. Hispanic adults had decreased odds of having no friends associated with signs of physical disorder, while no associations were found among older White adults. White adults had higher odds of isolation from in-person visits when living in neighborhoods with signs of physical disorder, whereas no association was observed among older Black and Hispanic adults., Conclusions: This study elucidates the role of neighborhood characteristics in shaping social isolation dynamics among older adults. Furthermore, the observed moderation effects of race/ethnicity suggest the need for culturally sensitive interventions tailored to address social isolation within specific neighborhood and racial contexts., (© 2024. The Author(s).)

Background: The APOE gene is the strongest genetic risk factor for late-onset Alzheimer's Disease (LOAD). However, the gene regulatory mechanisms at this locus remain incompletely characterized., Methods: To identify novel AD-linked functional elements within the APOE locus, we integrated SNP variants with multi-omics data from human postmortem brains including 2,179 RNA-seq samples from 3 brain regions and two ancestries (European and African), 667 DNA methylation samples, and ChIP-seq samples. Additionally, we plotted the expression trajectory of APOE transcripts in human brains during development., Results: We identified an AD-linked APOE transcript (jxn1.2.2) particularly observed in the dorsolateral prefrontal cortex (DLPFC). The APOE jxn1.2.2 transcript is associated with brain neuropathological features, cognitive impairment, and the presence of the APOE4 allele in DLPFC. We prioritized two independent functional SNPs (rs157580 and rs439401) significantly associated with jxn1.2.2 transcript abundance and DNA methylation levels. These SNPs are located within active chromatin regions and affect brain-related transcription factor-binding affinities. The two SNPs shared effects on the jxn1.2.2 transcript between European and African ethnic groups., Conclusion: The novel APOE functional elements provide potential therapeutic targets with mechanistic insight into the disease etiology., (© 2024. The Author(s).)

Background: Long-acting injectable cabotegravir plus rilpivirine (LAI CAB/RPV) has several potential benefits over daily oral formulations for HIV treatment, including the potential to facilitate long-term adherence and reduce pill fatigue. We aimed to assess facilitators of and barriers to LAI CAB/RPV implementation and delivery through the perspectives of physicians and clinical staff, and the experiences of LAI CAB/RPV use among people living with HIV (PLWH) at a Ryan-White supported safety-net clinic in North Texas., Methods: We conducted semi-structured interviews with recruited clinic staff (physicians, nurses, and support staff) involved with LAI CAB/RPV implementation and PLWH who switched to LAI CAB/RPV and consented to participate in individual interviews. Data were collected from July to October 2023. Our interview guide was informed by the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM), and Proctor Implementation Outcomes frameworks. Qualitative data were analyzed using a rapid qualitative analysis approach to summarize key themes., Results: We recruited and interviewed 15 PLWH who transitioned to LAI CAB/RPV and 11 clinic staff serving these patients. PLWH conveyed that emotional and informational support from family or a trusted clinician influenced their decision to switch to LAI CAB/RPV. PLWH also reported that injectable treatment was more effective, convenient, and acceptable than oral antiretroviral therapy. Clinic staff and physicians reported that staff training, pharmacist-led medication switches, flexible appointments, refrigeration space and designated room for injection delivery facilitated implementation. Clinic staff cited medication costs, understaffing, insurance prior authorization requirements, and lack of medication access through state drug assistance programs as critical barriers., Conclusions: Our study offers insights into real-world experiences with LAI usage from the patient perspective and identifies potential strategies to promote LAI CAB/RPV uptake. The barriers to and facilitators of LAI CAB/RPV program implementation reported by clinic staff in our study may be useful for informing strategies to optimize LAI CAB/RPV programs., (© 2024. The Author(s).)

Background: RNA sequencing (RNA-Seq) offers profound insights into the complex transcriptomes of diverse biological systems. However, standard differential expression analysis pipelines based on DESeq2 and edgeR encounter challenges when applied to the immediate early transcriptomes of Chlamydia spp., obligate intracellular bacteria. These challenges arise from their reliance on assumptions that do not hold in scenarios characterized by extensive transcriptomic activation and limited repression., Results: Standard analyses using unique chlamydial RNA-Seq reads alone identify nearly 300 upregulated and about 300 downregulated genes, significantly deviating from actual RNA-Seq read trends. By incorporating both chlamydial and host reads or adjusting for total sequencing depth, the revised normalization methods each detected over 700 upregulated genes and 30 or fewer downregulated genes, closely aligned with observed RNA-Seq data. Further validation through qRT-PCR analysis confirmed the effectiveness of these adjusted approaches in capturing the true extent of transcriptomic activation during the immediate early phase of chlamydial infection., Conclusions: This study highlights the limitations of standard RNA-Seq analysis tools in scenarios with extensive transcriptomic activation, such as in Chlamydia spp. during early infection. Our revised normalization methods, incorporating host reads or total sequencing depth, provide a more accurate representation of gene expression dynamics. These approaches may inform similar adjustments in other systems with unbalanced gene expression dynamics, enhancing the accuracy of transcriptomic analysis., (© 2024. The Author(s).)

Background: Older adult women often do not engage in sufficient physical activity (PA) and can encounter biological changes that exacerbate the negative effects of inadequate activity. Wearable activity monitors can facilitate PA initiation, but evidence of sustained behavior change is lacking. Supplementing wearable technologies with intervention content that evokes enjoyment, interest, meaning, and personal values associated with PA may support long term adherence. In this paper, we present the protocol of an NIA-funded study designed to evaluate the efficacy of CHALLENGE for increasing step count and motivation for PA in insufficiently active older women (Challenges for Healthy Aging: Leveraging Limits for Engaging Networked Game-based Exercise). CHALLENGE uses social media to supplement wearable activity monitors with the autonomy-supportive frame of a game. We hypothesize that CHALLENGE will engender playful experiences that will improve motivation for exercise and lead to sustained increases in step count., Methods: We will recruit 300 healthy, community dwelling older adult women on a rolling basis and randomize them to receive either the CHALLENGE intervention (experimental arm) or an activity monitor-only intervention (comparison arm). Participants in both groups will receive a wearable activity monitor and personalized weekly feedback emails. In the experimental group, participants will also be added to a private Facebook group, where study staff will post weekly challenges that are designed to elicit playful experiences while walking. Assessments at baseline and 6, 12, and 18 months will measure PA and motivation-related constructs. We will fit linear mixed-effects models to evaluate differences in step count and motivational constructs, and longitudinal mediation models to evaluate if interventional effects are mediated by changes in motivation. We will also conduct thematic content analysis of text and photos posted to Facebook and transcripts from individual interviews., Discussion: By taking part in a year-long intervention centered on imbuing walking behaviors with playful and celebratory experiences, participating older adult women may internalize changes to their identity and relationship with PA that facilitate sustained behavior change. Study results will have implications for how we can harness powerful and increasingly ubiquitous technologies for health promotion to the vast and growing population of older adults in the U.S. and abroad., Trial Registration: ClinicalTrials.gov Identifier NCT04095923. Registered September 17th, 2019., (© 2024. The Author(s).)

Background: Qualitative methods are a critical tool for enhancing implementation planning and tailoring, yet rapid turn-around of qualitative insights can be challenging in large implementation trials. The Department of Veterans Affairs-funded EMPOWER 2.0 Quality Enhancement Research Initiative (QUERI) is conducting a hybrid type 3 effectiveness-implementation trial comparing the impact of Replicating Effective Programs (REP) and Evidence-Based Quality Improvement (EBQI) as strategies for implementing three evidence-based practices (EBPs) for women Veterans. We describe the development of the Rapid Implementation Feedback (RIF) report, a pragmatic, team-based approach for the rapid synthesis of qualitative data to aid implementation planning and tailoring, as well as findings from a process evaluation of adopting the RIF report within the EMPOWER 2.0 QUERI., Methods: Trained qualitative staff conducted 125 semi-structured pre-implementation interviews with frontline staff, providers, and leadership across 16 VA sites between October 2021 and October 2022. High-priority topic domains informed by the updated Consolidated Framework for Implementation Research were selected in dialogue between EMPOWER 2.0 implementation and evaluation teams, and relevant key points were summarized for each interview to produce a structured RIF report, with emergent findings about each site highlighted in weekly written and verbal communications. Process evaluation was conducted to assess EMPOWER 2.0 team experiences with the RIF report across pre-implementation data collection and synthesis and implementation planning and tailoring., Results: Weekly RIF updates supported continuous EMPOWER 2.0 team communication around key findings, particularly questions and concerns raised by participating sites related to the three EBPs. Introducing the RIF report into team processes enhanced: team communication; quality and rigor of qualitative data; sensemaking around emergent challenges; understanding of site readiness; and tailoring of REP and EBQI implementation strategies. RIF report findings have facilitated rapid tailoring of implementation planning and rollout, supporting increased responsiveness to sites' needs and concerns., Conclusions: The RIF report provides a structured strategy for distillation of time-sensitive findings, continuous team communication amid a complex multi-site implementation effort, and effective tailoring of implementation rollout in real-time. Use of the RIF report may also support trust-building by enhancing responsiveness to sites during pre- and early implementation., Trial Registration: Enhancing Mental and Physical Health of Women Veterans (NCT05050266); https://clinicaltrials.gov/study/NCT05050266?term=EMPOWER%202.0&rank=1 Date of registration: 09/09/2021., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Prolonged exposure (PE) therapy is widely recognized as an effective treatment for post-traumatic stress disorder (PTSD) and is often considered one of the primary options for addressing this condition. Nevertheless, a significant proportion of patients (30-51%) fail to demonstrate clinically significant symptom changes. One of the reasons is that a high proportion of patients drop out from treatment, which often lasts for a minimum of 3-4 months. Hence, there is an urgent need for PTSD treatments that can be delivered to decrease dropout rates. A more intensive PE treatment approach has been suggested to decrease dropout rates and in addition achieve faster recovery rates and has shown promising effects on reducing PTSD symptoms but needs to be tested against firsthand treatment., Methods: This single-blind, randomized controlled trial (N = 140) will compare an intensive delivery format of prolonged exposure (iPE) against standard weekly delivered sessions of PE. The primary outcome is change on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). Secondary outcomes include self-rated measures of symptoms of PTSD and complex PTSD, depression and quality of life, speed of recovery, cost effectiveness, dropout rates, and adverse events., Discussion: This study will be the first to compare iPE with first-line treatment in a psychiatric outpatient setting. One of the key strengths of this study lies in its implementation within a clinical setting and the broad eligibility criteria. Additionally, the utilization of gold-standard assessment measures ensures the accuracy and reliability of the outcomes. However, several potential challenges may arise during the study's execution. These challenges may include difficulties in participant recruitment, ensuring adequate participant retention, adherence to the treatment protocol, and maintaining therapist retention mostly due to recruitment taking place at one single clinic., Trial Registration Number: Clinicaltrials.gov NCT05934175. Registered on June 6, 2023. Open Science Framework (OSF) https://osf.io/7qsb3 . Registered on September 2, 2023., (© 2024. The Author(s).)

Background: Nearly two-thirds of family caregivers of persons living with Alzheimer's disease or related dementias (AD/ADRD) provide complex care, including medical care. Family caregivers typically receive little to no training on how to provide this care. Furthermore, family caregivers simultaneously grapple with the presence of behavioral and psychological symptoms of dementia (BPSD), diminished communication abilities, and comorbidities such as diabetes. We developed Learning Skills Together (LST), a 6-week digitally delivered psychoeducational program, to facilitate family caregiver abilities to administer complex care tasks. The goal of the present study is to test the efficacy of LST and to reduce adverse outcomes associated with caregiving, such as depressive symptomology and negative appraisal of BPSD., Methods: To test the efficacy of LST, we will conduct a two-arm single-site randomized controlled trial (RCT) with N = 200 family caregivers of persons living with AD/ADRD. Eligible family caregivers will be randomly assigned to participate in either the LST intervention or a structurally equivalent control condition focused on healthy living. All family caregivers will complete four surveys, including a baseline survey administered prior to randomization, a post-intervention survey, and a 3- and 6-month follow-up survey to assess change in study outcomes. Between-group comparisons of each outcome will be evaluated using generalized estimating equation models. Mediation analyses will assess family caregiver self-efficacy as the intervention's mechanism of change in depressive symptomology and BPSD. We will also examine caregiver race, ethnicity, and gender as effect modifiers of the intervention., Discussion: LST findings will inform the field of AD/ADRD and caregiving regarding optimally supporting family caregivers in managing complex care tasks. If efficacious, the LST intervention will support family caregivers in preserving their own mental health while providing complex care., Trial Registration: Clinical Trials.gov NCT05846984 . This study was registered on May 6, 2023., (© 2024. The Author(s).)

Background: Lagenidium deciduum is an oomycete that can cause infections in mammals that present similarly to pythiosis and mucormycosis. Most of the existing case reports have occurred in canines and have been fatal. In animals, medical therapy has not been successful, so surgical excision is the mainstay of treatment. Lagenidium sp. infections in humans are rare. There is only one case of a human Lagenidium sp. infection in the literature, and it presented as an ocular infection. The human ocular infection was resistant to medical therapy and required a penetrating keratoplasty for cure. Additional reports of effective therapy are needed to guide management of this emerging pathogen. We present the first case of a cutaneous Lagenidium deciduum infection in a human patient, which is also the first documented case of a Lagenidium deciduum infection in an immunocompromised host of any species., Case Presentation: An 18-year-old female with relapsed acute myeloid leukemia, awaiting a haploidentical stem cell transplant, presented with erythematous cutaneous lesions on her left hip and bilateral buttocks that enlarged and blackened over several days. About 1 week later, boil-like lesions appeared on her bilateral buttocks. The skin lesions were initially presumed to be bacterial in origin, so the patient was treated with clindamycin and cefepime with little improvement. Upon further investigation, fungal cultures and skin biopsies revealed aseptate hyphae, so the patient was switched to isavuconazole and amphotericin B due to concern for mucormycosis. Phenotypic characterization and DNA sequencing were performed by the Fungus Testing Laboratory, University of Texas Health Science Center at San Antonio, which identified the causal fungal organism as Lagenidium deciduum. All of her cutaneous lesions were surgically excised, and the patient was treated with micafungin, terbinafine, doxycycline, and azithromycin. Micafungin and terbinafine were continued until she achieved engraftment post-transplant., Conclusions: We report the first successful treatment of a human Lagenidium infection in an immunocompromised host through a combination of aggressive surgical excision and prolonged antifungal therapy during the prolonged neutropenia associated with allogeneic stem cell transplant. Prompt diagnosis and management may prevent disseminated oomycosis., (© 2024. The Author(s).)

Background: Ectopic cervical thymoma (ECT) is an extremely rare tumor, especially in association with myasthenia gravis (MG)., Case Presentation: We report a case of myasthenia gravis with an ectopic thymoma in the neck, whose myasthenic symptoms significantly improved after complete removal of the mass. A 55-year-old woman with generalized myasthenia gravis (MG) experienced worsening neuromuscular weakness after abruptly discontinuing pyridostigmine. Testing revealed acetylcholine receptor-antibody (AChR-Ab) positivity and a cervical mass initially thought to be thyroid or parathyroid was identified as a thymoma, type A. Post-surgery and radiation therapy, her myasthenic symptoms improved significantly with less prednisone and pyridostigmine requirements over time and no need for additional immunotherapies., Conclusions: Diagnosing ECTs is challenging due to rarity, atypical locations, and inconclusive fine needle aspiration cytology (FNAC) results, often misinterpreted as thyroid or parathyroid lesions. As proper management of patients with MG, including thymectomy, offers favorable clinical outcomes such as significant improvement in myasthenic complaints and reduced immunosuppressive medication requirements, clinicians should be vigilant of the ectopic locations of thymomas to ensure timely diagnosis and intervention., (© 2024. The Author(s).)

The adoption and maintenance of physical activity (PA) is an important health behavior. This paper presents the first comprehensive empirical test of the Physical Activity Adoption and Maintenance (PAAM) model, which proposes that a combination of explicit (e.g., intention) and implicit (e.g., habit,, affect) self-regulatory processes is involved in PA adoption and maintenance. Data were collected via online questionnaires in English, German, and Italian at two measurement points four weeks apart. The study included 422 participants (M age = 25.3, SD age = 10.1; 74.2% women) from Germany, Switzerland, Italy, Canada, and the U.S. The study results largely supported the assumptions of the PAAM model, indicating that intentions and habits significantly mediate the effects of past PA on future PA. In addition, the effect of past PA on future PA was shown to be significant through a mediation chain involving affect and habit. Although the hypothesis that trait self-regulation moderates the intention-behavior relationship was not supported, a significant moderating effect of affect on the same relationship was observed. The results suggest that interventions targeting both explicit and implicit processes may be effective in promoting PA adoption and maintenance., (© 2024. The Author(s).)

Background: Metagenomic profiling algorithms commonly rely on genomic differences between lineages, strains, or species to infer the relative abundances of sequences present in a sample. This observation plays an important role in the analysis of diverse microbial communities, where targeted sequencing of 16S and 18S rRNA, both well-known hypervariable genomic regions, have led to insights into microbial diversity and the discovery of novel organisms. However, the variable nature of discriminatory regions can also act as a double-edged sword, as the sought-after variability can make it difficult to design primers for their amplification through PCR. Moreover, the most variable regions are not necessarily the most informative regions for the purpose of differentiation; one should focus on regions that maximize the number of lineages that can be distinguished., Results: Here we present AmpliDiff, a computational tool that simultaneously finds highly discriminatory genomic regions in viral genomes of a single species, as well as primers allowing for the amplification of these regions. We show that regions and primers found by AmpliDiff can be used to accurately estimate relative abundances of SARS-CoV-2 lineages, for example in wastewater sequencing data. We obtain errors that are comparable with using whole genome information to estimate relative abundances. Furthermore, our results show that AmpliDiff is robust against incomplete input data and that primers designed by AmpliDiff also bind to genomes sampled months after the primers were selected., Conclusions: With AmpliDiff we provide an effective, cost-efficient alternative to whole genome sequencing for estimating lineage abundances in viral metagenomes., (© 2024. The Author(s).)

Background: The Limb Girdle Muscular Dystrophies (LGMDs) are characterized by progressive weakness of the shoulder and hip girdle muscles as a result of over 30 different genetic mutations. This study is designed to develop clinical outcome assessments across the group of disorders., Methods/design: The primary goal of this study is to evaluate the utility of a set of outcome measures on a wide range of LGMD phenotypes and ability levels to determine if it would be possible to use similar outcomes between individuals with different phenotypes. We will perform a multi-center, 12-month study of 188 LGMD patients within the established Genetic Resolution and Assessments Solving Phenotypes in LGMD (GRASP-LGMD) Research Consortium, which is comprised of 11 sites in the United States and 2 sites in Europe. Enrolled patients will be clinically affected and have mutations in CAPN3 (LGMDR1), ANO5 (LGMDR12), DYSF (LGMDR2), DNAJB6 (LGMDD1), SGCA (LGMDR3), SGCB (LGMDR4), SGCD (LGMDR6), or SGCG (LGMDR5, or FKRP-related (LGMDR9)., Discussion: To the best of our knowledge, this will be the largest consortium organized to prospectively validate clinical outcome assessments (COAs) in LGMD at its completion. These assessments will help clinical trial readiness by identifying reliable, valid, and responsive outcome measures as well as providing data driven clinical trial decision making for future clinical trials on therapeutic agents for LGMD. The results of this study will permit more efficient clinical trial design. All relevant data will be made available for investigators or companies involved in LGMD therapeutic development upon conclusion of this study as applicable., Trial Registration: Clinicaltrials.gov NCT03981289; Date of registration: 6/10/2019., (© 2024. The Author(s).)

Diabetic retinopathy (DR) affects about 200 million people worldwide, causing leakage of blood components into retinal tissues, leading to activation of microglia, the resident phagocytes of the retina, promoting neuronal and vascular damage. The microglial receptor, CX3CR1, binds to fractalkine (FKN), an anti-inflammatory chemokine that is expressed on neuronal membranes (mFKN), and undergoes constitutive cleavage to release a soluble domain (sFKN). Deficiencies in CX3CR1 or FKN showed increased microglial activation, inflammation, vascular damage, and neuronal loss in experimental mouse models. To understand the mechanism that regulates microglia function, recombinant adeno-associated viral vectors (rAAV) expressing mFKN or sFKN were delivered to intact retinas prior to diabetes. High-resolution confocal imaging and mRNA-seq were used to analyze microglia morphology and markers of expression, neuronal and vascular health, and inflammatory mediators. We confirmed that prophylactic intra-vitreal administration of rAAV expressing sFKN (rAAV-sFKN), but not mFKN (rAAV-mFKN), in FKN KO retinas provided vasculo- and neuro-protection, reduced microgliosis, mitigated inflammation, improved overall optic nerve health by regulating microglia-mediated inflammation, and prevented fibrin(ogen) leakage at 4 weeks and 10 weeks of diabetes induction. Moreover, administration of sFKN improved visual acuity. Our results elucidated a novel intervention via sFKN gene therapy that provides an alternative pathway to implement translational and therapeutic approaches, preventing diabetes-associated blindness., (© 2024. The Author(s).)

Introduction: Many physicians including emergency medicine physicians report insufficient training and education on prescribing buprenorphine for opioid use disorder. As emergency departments implement buprenorphine induction protocols, educational sessions can provide physicians with further familiarity with the treatment of opioid use disorder. This quality improvement project aimed to address the barrier of physician education in the implementation of buprenorphine initiation in the emergency department and presents a model for resident-led education sessions of emergency medicine physicians., Methods: The project was a resident-led educational quality improvement project on educating members of the Department of Emergency Medicine on buprenorphine induction. The thirty-minute educational session included a pre-test survey, lecture, practice case workshop, questions, post-test survey, and a discussion. The survey questions were designed for physicians including residents and faculty, but medical students were invited to complete the session., Results: Physicians including faculty and resident physicians responded positively to the educational survey, with an increase from 42.5 to 100% responding that they understood the risks and benefits of prescribing buprenorphine in the emergency department pre and post-survey respectively. Based on post-survey results, 88.5% of physicians responded that they planned to prescribe buprenorphine in the emergency department for patients meeting clinical criteria after completing the educational session., Conclusion: The results suggest that a resident-led training session can encourage peer involvement in buprenorphine induction to treat opioid use disorder in the emergency department., (© 2024. The Author(s).)

Background: Older adults, as the population considered at increased risk for severe COVID-19, were the most impacted by social isolation. Thus, this study aimed to assess the salivary immune/inflammatory response of older adults before and during the COVID-19 pandemic., Methods: A cohort of 11 older adults (mean age 66.8 ± 6.1) was followed at three different time points: before (S1) and after 6 (S2) and 20 months (S3) of the beginning of the COVID-19 pandemic in Brazil. Unstimulated saliva samples were obtained to assess the levels of antibodies (secretory IgA, IgG and IgM) by ELISA and cytokines (IL-2, IL-5, IL-6, IL-8 and IL-10, TSLP, IFN-γ, TNF-α) by multiplex analysis. Significant differences were evaluated using the Kruskal-Wallis test with Dunn's post-test., Results: None volunteer presented periodontal disease or caries. All volunteers received at least two doses of the COVID-19 vaccines after S2 and before S3. A tendency to increase salivary levels of SIgA and IgM at S2 and of IgG at S3 were observed compared to the values found at S1 and S2. Significantly decreased levels of IL-2 and IL-5 were found at S2 and S3 (p < 0.001) time points. Lower levels of IFN-γ were found at S2 as compared to the values observed at S1 (p < 0.01). A significant decrease in the IFN-γ/IL-10 ratio was found at S2 (p < 0.01). When assessing the Th1/Th2 ratios, a significant decrease was found in the IFN-γ/TSLP ratio at S2 (p < 0.001) and S3 (p < 0.001) when compared to the values at S1. In addition, a significant increase was observed in the TNF-α/IL-5 ratio at S2 (p < 0.001) and S3 (p < 0.001) in comparison to the values at S1. In a similar way, an increase in the TNF-α/IL-6 ratio (Fig. 5E) was observed at S3 (p < 0.001) when compared to the values at S1., Conclusions: Overall, this study provides valuable insights into the impact of COVID-19-induced social isolation on immune/inflammatory responses in the upper airway mucosa, particularly those present in oral cavity, of older adults. It demonstrates that a controlled shift in Th1 and Th2 immune responses, both during infection and post-vaccination, can create favorable conditions to combat viral infections without exacerbating the immune response or worsening the pathology., (© 2024. The Author(s).)

Objectives: To develop a prediction model of mortality in pediatric trauma-based injuries. Our secondary objective was to transform this model into a translational tool for clinical use., Study Design: A retrospective cohort study of children ≤ 18 years was derived from the National Trauma Data Bank between the years of 2007 to 2015. The goal was to identify clinical or physiologic variables that would serve as predictors for pediatric death. Data was split into a development cohort (80%) to build the model and then tested in an internal validation cohort (20%) and a temporal cohort. The area under the receiver operating characteristic curve (AUC) was assessed for the new model., Results: In 693,192 children, the mortality rate was 1.4% (n = 9,785). Most subjects were male (67%), White (65%), and incurred an unintentional injury (92%). The proposed model had an AUC of 96.4% (95% CI: 95.9%-96.9%). In contrast, the Injury Severity Score yielded an AUC of 92.9% (95% CI: 92.2%-93.6%), while the Revised Trauma Score resulted in an AUC of 95.0% (95% CI: 94.4%-95.6%)., Conclusion: The TRAGIC + Model (Temperature, Race, Age, GCS, Injury Type, Cardiac-systolic blood pressure + Mechanism of Injury and Sex) is a new pediatric mortality prediction model that leverages variables easily obtained upon trauma admission., (© 2023. The Author(s).)

Background and Objectives: Because much of the work in academic medicine is done by committee, early career URiM faculty, are often asked to serve on multiple committees, including diversity work that may not be recognized as important. They may also be asked to serve on committees to satisfy a diversity "check box," and may be asked more often than their non-URiM peers to serve in this capacity. We sought to describe the committee experiences of early career URiM faculty, hypothesizing that they may see committee service as a minority tax., Methods: Participants in the Leadership through Scholarship Fellowship (LTSF) were asked to share their experiences with committee service in their careers after participating in a faculty development discussion. Their responses were analyzed and reported using qualitative, open, axial, and abductive reasoning methods., Results: Four themes, with eight sub-themes (in parenthesis), emerged from the content analysis of the LTSF fellows responses to the prompt: Time commitment (Timing of committee work and lack of protected time for research and scholarship), URiM Committee service (Expectation that URiM person will serve on committees and consequences for not serving), Mentoring issues (no mentoring regarding committee service, faculty involvement is lacking and the conflicting nature of committee work) and Voice (Lack of voice or acknowledgement)., Conclusions: Early career URiM faculty reported an expectation of serving on committees and consequences for not serving related to their identity, but other areas of committee service they shared were not connected to their URiM identity. Because most of the experiences were not connected to the LTSF fellows' URiM identity, this group has identified areas of committee service that may affect all early career faculty. More research is necessary to determine how committee service affects URiM and non-URiM faculty in academic family medicine., (© 2023. The Author(s).)

Background: Numerous upper airway anatomy characteristics are risk factors for sleep apnea, which affects 26% of older Americans, and more severe sleep apnea is associated with cognitive impairment. This study explores the pathophysiology and links between upper airway anatomy, sleep, and cognition., Methods: Participants in the Multi-Ethnic Study of Atherosclerosis underwent an upper airway MRI, polysomnography to assess sleep measures including the apnea-hypopnea index (AHI) and completed the Cognitive Abilities Screening Instrument (CASI). Two model selection techniques selected from among 67 upper airway measures those that are most strongly associated with CASI score. The associations of selected upper airway measures with AHI, AHI with CASI score, and selected upper airway anatomy measures with CASI score, both alone and after adjustment for AHI, were assessed using linear regression., Results: Soft palate volume, maxillary divergence, and upper facial height were significantly positively associated with higher CASI score, indicating better cognition. The coefficients were small, with a 1 standard deviation (SD) increase in these variables being associated with a 0.83, 0.75, and 0.70 point higher CASI score, respectively. Additional adjustment for AHI very slightly attenuated these associations. Larger soft palate volume was significantly associated with higher AHI (15% higher AHI (95% CI 2%,28%) per SD). Higher AHI was marginally associated with higher CASI score (0.43 (95% CI 0.01,0.85) per AHI doubling)., Conclusions: Three upper airway measures were weakly but significantly associated with higher global cognitive test performance. Sleep apnea did not appear to be the mechanism through which these upper airway and cognition associations were acting. Further research on the selected upper airway measures is recommended., (© 2023. The Author(s).)

Background: Insulin resistance (IR) is a major risk factor for Alzheimer's disease (AD) dementia. The mechanisms by which IR predisposes to AD are not well-understood. Epigenetic studies may help identify molecular signatures of IR associated with AD, thus improving our understanding of the biological and regulatory mechanisms linking IR and AD., Methods: We conducted an epigenome-wide association study of IR, quantified using the homeostatic model assessment of IR (HOMA-IR) and adjusted for body mass index, in 3,167 participants from the Framingham Heart Study (FHS) without type 2 diabetes at the time of blood draw used for methylation measurement. We identified DNA methylation markers associated with IR at the genome-wide level accounting for multiple testing (P < 1.1 × 10 -7 ) and evaluated their association with neurological traits in participants from the FHS (N = 3040) and the Religious Orders Study/Memory and Aging Project (ROSMAP, N = 707). DNA methylation profiles were measured in blood (FHS) or dorsolateral prefrontal cortex (ROSMAP) using the Illumina HumanMethylation450 BeadChip. Linear regressions (ROSMAP) or mixed-effects models accounting for familial relatedness (FHS) adjusted for age, sex, cohort, self-reported race, batch, and cell type proportions were used to assess associations between DNA methylation and neurological traits accounting for multiple testing., Results: We confirmed the strong association of blood DNA methylation with IR at three loci (cg17901584-DHCR24, cg17058475-CPT1A, cg00574958-CPT1A, and cg06500161-ABCG1). In FHS, higher levels of blood DNA methylation at cg00574958 and cg17058475 were both associated with lower IR (P = 2.4 × 10 -11 and P = 9.0 × 10 -8 ), larger total brain volumes (P = 0.03 and P = 9.7 × 10 -4 ), and smaller log lateral ventricular volumes (P = 0.07 and P = 0.03). In ROSMAP, higher levels of brain DNA methylation at the same two CPT1A markers were associated with greater risk of cognitive impairment (P = 0.005 and P = 0.02) and higher AD-related indices (CERAD score: P = 5 × 10 -4 and 0.001; Braak stage: P = 0.004 and P = 0.01)., Conclusions: Our results suggest potentially distinct epigenetic regulatory mechanisms between peripheral blood and dorsolateral prefrontal cortex tissues underlying IR and AD at CPT1A locus., (© 2023. The Author(s).)

Background: Uganda has among the highest fertility rates in the world and multi-level barriers contribute to the low contraceptive use., Objective: The objective of this study was to develop a culturally and socially relevant, community-based intervention to increase contraceptive use among couples in rural Uganda through community-engaged research methods. This study reports on the community-engaged research that informed the intervention's content and structure and the final content of the intervention; the evaluation of the pilot intervention will be reported upon completion., Methods: An intervention steering committee of community stakeholders reviewed the initially proposed intervention content and approach. Four (4) gender-segregated focus groups were conducted with twenty-six (26) men and women who had an unmet need for family planning. Fifteen key-informant interviews were conducted with community leaders and family planning stakeholders. Finally, the 4-session intervention was pilot tested with a cohort of couples (N = 7) similar in demographics to the target sample of the future pilot intervention trial. Qualitative data were analyzed thematically., Results: Findings included the identification of community beliefs to reshape in order to increase family planning acceptance, as well as strategies to engage men, acceptable approaches for community leader involvement in the intervention to endorse family planning, and methods for managing gender dynamics and minimizing risk of unintended negative consequences of participation. The findings were used to inform the ideal structure and format of the intervention, including the distribution of contraceptives directly during group sessions, and identified the need to strengthen health worker capacity to provide Long-Acting Reversable Contraceptives (LARCs) as part of the intervention., Conclusions: These findings were used to refine an intervention before a larger scale pilot test of its feasibility, acceptability, and potential efficacy. They can inform other multi-level family planning interventions in similar settings and the methods can be adopted by others to increase the feasibility, acceptability, and cultural relevance of interventions., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Purpose: To investigate foveal changes in infants with ROP not requiring treatment(nROP) and ROP infants needing treatment (tROP) using a handheld SD-OCT device., Method: We performed horizontal SD-OCT scans through the fovea in 156 eyes of 81 infants diagnosed with ROP. Foveal immaturity indices including the presence of inner retinal layers (IRL), absence of foveal outer nuclear layers widening (ONL) and attenuation of hyperreflective outer segment layers (OS), presence and type of cystoid macular edema (CME), epiretinal membrane (ERM), foveal pit depth (FPD), foveal pit width (FPW) and central foveal thickness (CFT) were calculated. The multivariate logistic regression model was used to predict the need for treatment based on OCT measurements., Results: The shape of the foveolar pit was not significantly different among tROP and nROP groups (P-value = 0.287, Chi-square test). IRL extrusion was incomplete in both tROP and nROP groups (P-value = 0.0.41, Chi-square test). Nevertheless, the presence of thicker IRL was more frequent in the nROP group in comparison with the tROP group (100% vs.64.8%, P-value = 0.001). CME was observed in 29% of eyes in the tROP group and 40% of eyes in the nROP group; however, this difference was not statistically significant (P-value = 0.32, Chi-square test). ERM was detected in 15 (75%) and 84 (65.6%) eyes in the nROP and tROP groups, respectively (P-value = 0.39, Chi-square test). Multivariate logistic regression analyses showed that the need for treatment was significantly associated with gestational age (GA), CFT and FPD (P-values 0.001 and 0.002 respectively)., Conclusions: This study demonstrated GA, foveal pit depth and the central foveal thickness could accurately predict the need for treatment with sensitivity, specificity, and diagnostic accuracy of 97%, 65% and 91.7% respectively., (© 2023. Brazilian Retina and Vitreous Society.)

Background: Intimate partner violence (IPV) is a significant public health issue, and when experienced during pregnancy, IPV substantially harms maternal health. Still, limited research has examined how IPV may influence prenatal oral health and dental care utilization. This study investigates the relationship between IPV during pregnancy and women's oral health experiences., Data: Data are from 31 states from 2016-2019 in the United States that participated in the Pregnancy Risk Assessment Monitoring System (N = 85,289)-a population-based surveillance system of live births conducted annually by the Centers for Disease Control and Prevention and state health departments. Multivariable logistic regression analyses were used to examine the association between physical IPV during pregnancy (measured by being pushed, hit, slapped, kicked, choked, or physically hurt any other way by a current or ex-husband/partner) and various oral health experiences., Findings: Women who experienced prenatal physical IPV reported worse oral health experiences during pregnancy, including being more likely to report not knowing it was important to care for their teeth, not talking about dental health with a provider, needing to see a dentist for a problem, going to see a dentist for a problem, as well as having more unmet dental care needs., Conclusions: Together, these findings indicate that women who experience physical IPV during pregnancy have lower knowledge of prenatal oral health care, more oral health problems, and greater unmet dental care needs. Given the risk of IPV and oral health problems for maternal and infant health, the study findings point to greater attention toward the oral health needs of IPV-exposed pregnant women., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Chronic insomnia is the most prevalent sleep disorder among military service members, and it compromises readiness, performance, and physical and mental health. Cognitive behavioral treatment for insomnia (CBTI) is the standard of care for the treatment of insomnia recommended by the VA/DoD Clinical Practice Guideline, the American Academy of Sleep Medicine, and the American College of Physicians. CBTI is highly effective but has limited scalability. It is often unavailable in clinical settings where service members receive sleep care. Digital technologies offer unique opportunities to scale and broaden the geographic reach of CBTI services and support increased patient access and engagement in behavioral sleep care. This study aims to evaluate the impact and acceptability of digital CBTI hubs to augment military treatment facilities' capabilities in behavioral sleep medicine., Methods: This is a multi-site, non-inferiority randomized clinical trial designed to compare the effects of in-person (face-to-face or virtual) insomnia care as usual at three military sleep clinics versus CBTI delivered remotely and asynchronously through digital CBTI hubs. Digital CBTI hubs are led by licensed, certified clinicians who use NOCTEM's® evidence-based clinical decision support platform COAST™ (Clinician Operated Assistive Sleep Technology). Changes in insomnia severity and daytime symptoms of depression and anxiety will be compared at baseline, at 6-8 weeks, and at 3-month follow-up. Patient satisfaction with insomnia care as usual versus digital CBTI hubs will also be examined. We hypothesize that digital CBTI hubs will be non-inferior to insomnia care as usual for improvements in insomnia and daytime symptoms as well as patient satisfaction with insomnia care., Discussion: Digital technology has a high potential to scale CBTI accessibility and delivery options required to meet the insomnia care needs of military service members. Digital CBTI hubs using COAST offer a novel approach to broaden service members' access to CBTI and to serve as an augmentation strategy for existing sleep services at military treatment facilities. The pragmatic approach leveraging technology in this trial has the potential to rapidly inform clinical practice within the Defense Health Agency as well as other healthcare systems., Trial Registration: ClinicalTrials.gov NCT05490550. Registered on 14 July 2023., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The Eyes Absent (EYA) family of proteins is an atypical group of four dual-functioning protein phosphatases (PP), which have been linked to many vital cellular processes and organogenesis pathways. The four family members of this PP family possess transcriptional activation and phosphatase functions, with serine/threonine and tyrosine phosphatase domains. EYA4 has been associated with several human cancers, with tumor-suppressing and tumor-promoting roles. However, EYA4 is the least well-characterized member of this unique family of PP, with its biological functions and molecular mechanisms in cancer progression, particularly in breast cancer, still largely unknown. In the present study, we found that the over-expression of EYA4 in breast tissue leads to an aggressive and invasive breast cancer phenotype, while the inhibition of EYA4 reduced tumorigenic properties of breast cancer cells in vitro and in vivo. Cellular changes downstream of EYA4, including cell proliferation and migration, may explain the increased metastatic power of breast cancer cells over-expressing EYA4. Mechanistically, EYA4 prevents genome instability by inhibiting the accumulation of replication-associated DNA damage. Its depletion results in polyploidy as a consequence of endoreplication, a phenomenon that can occur in response to stress. The absence of EYA4 leads to spontaneous replication stress characterized by the activation of the ATR pathway, sensitivity to hydroxyurea, and accumulation of endogenous DNA damage as indicated by increased γH2AX levels. In addition, we show that EYA4, specifically its serine/threonine phosphatase domain, plays an important and so far, unexpected role in replication fork progression. This phosphatase activity is essential for breast cancer progression and metastasis. Taken together, our data indicate that EYA4 is a novel potential breast cancer oncogene that supports primary tumor growth and metastasis. Developing therapeutics aimed at the serine/threonine phosphatase activity of EYA4 represents a robust strategy for killing breast cancer cells, to limit metastasis and overcome chemotherapy resistance caused by endoreplication and genomic rearrangements., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Point-of-care ultrasound (POCUS) can aid geriatricians in caring for complex, older patients. Currently, there is limited literature on POCUS use by geriatricians. We conducted a national survey to assess current POCUS use, training desired, and barriers among Geriatrics and Extended Care ("geriatric") clinics at Veterans Affairs Medical Centers (VAMCs)., Methods: We conducted a prospective observational study of all VAMCs between August 2019 and March 2020 using a web-based survey sent to all VAMC Chiefs of Staff and Chiefs of geriatric clinics., Results: All Chiefs of Staff (n=130) completed the survey (100% response rate). Chiefs of geriatric clinics ("chiefs") at 76 VAMCs were surveyed and 52 completed the survey (68% response rate). Geriatric clinics were located throughout the United States, mostly at high-complexity, urban VAMCs. Only 15% of chiefs responded that there was some POCUS usage in their geriatric clinic, but more than 60% of chiefs would support the implementation of POCUS use. The most common POCUS applications used in geriatric clinics were the evaluation of the bladder and urinary obstruction. Barriers to POCUS use included a lack of trained providers (56%), ultrasound equipment (50%), and funding for training (35%). Additionally, chiefs reported time utilization, clinical indications, and low patient census as barriers., Conclusions: POCUS has several potential applications for clinicians caring for geriatric patients. Though only 15% of geriatric clinics at VAMCs currently use POCUS, most geriatric chiefs would support implementing POCUS use as a diagnostic tool. The greatest barriers to POCUS implementation in geriatric clinics were a lack of training and ultrasound equipment. Addressing these barriers systematically can facilitate implementation of POCUS use into practice and permit assessment of the impact of POCUS on geriatric care in the future., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Purpose: Although a long-term goal of cancer therapy always has been the development of agents that selectively destroy cancer cells, more recent trends have been to seek secondary agents that sensitize cancer cells to existing treatment regimens. In this regard, the present study explored the possibility of using small molecule inhibitors of p38MAPK/MK2 stress signaling pathways as potential agents to enhance the sensitivity of cancer cells with abrogated G1 checkpoint to the DNA damaging agent etoposide by specifically targeting the DNA damage-induced G2 cell cycle checkpoint., Methods: We have applied CCK8 and FACS-based viability assays and cell cycle analysis to investigate the effect of small molecules SB203580 and MK2.III on the sensitivity of small cell lung cancer cells (SCLC) that lack the G1 checkpoint to the DNA damaging agent Etoposide when used in combination. We have also assessed the effectiveness of combination chemotherapy on tumor xenograft suppression with etoposide and MK2.III in immunosuppressed mice. In addition, additional CCK8 cell viability analysis of the MDA-MB-231 breast cancer cell line, and SW620, and SW480 colorectal cancer cell lines was performed., Results: Results suggest that etoposide produces a profound effect on the cell cycle profile of cells in a manner that is consistent with the degree of cell viability that is seen using the viable cell assay. Results of the co-treatment experiments revealed that the p38/MK2 kinase inhibitors SB203580 and MK2.III both enhanced the DNA-damaging effects of etoposide on NCI-H69 cell viability in vitro. Results revealed that in vivo MK2.III was able to act as a chemosensitizer when used in combination with etoposide making NCI-H69 lung cancer cells sensitive to chemotherapeutic drug by 45% compared to single usage of the drug. We also report that MK2.III sensitizes metastatic cell lines SW-620 and MDA-MB-231 to etoposide but does not increase the sensitivity of non-metastasizing SW-480 colorectal cells to DNA damaging agent in vitro., Conclusion: Findings reported in this study provide evidence that specific inhibitors of MK2 may indeed improve overall cancer therapy; however, their effectiveness depends on cell types., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Several systemic conditions can result in distinct degrees of salivary gland damage and consequent hypofunction. The development of successful management schemes is highly challenging due to the complexity of saliva. This study aimed to systematically map the literature on the physical stimulation of salivary glands for hyposalivation management and the response of individuals according to different systemic conditions causing salivary impairment., Methods: A systematic search in the literature was performed. Two reviewers independently selected clinical trials, randomized or not, that used physical stimulation to treat hyposalivation caused by systemic conditions. Studies evaluating healthy subjects without hyposalivation were included as controls. Single-arm clinical studies or case series were also included for protocol mapping (PRISMA extension for scoping reviews)., Results: Out of 24 included studies, 10 evaluated healthy subjects, from which 9 tested transcutaneous electrical nerve stimulation (TENS) and 1 tested acupuncture and electroacupuncture. Fourteen studies evaluated individuals with hyposalivation: 6 applied TENS, 6 applied low-level laser therapy (LLLT), and 2 applied acupuncture, carried out in post-chemotherapy, medication use, postmenopausal women, hemodialysis patients, smokers, diabetics, Sjögren's syndrome (SS). All showed increased salivation after treatment, except for two LLLT studies in individuals with SS., Conclusions: Among the different patient groups, individuals with Sjögren's syndrome (SS) exhibited the poorest responses, while those with medication-induced hyposalivation demonstrated the most favorable treatment outcomes, independently of the management strategy for saliva stimulation. It means that physical stimulation of salivary glands holds promise as an alternative for managing hyposalivation in cases of reversible gland damage. However, to make informed decisions in current practice, it is necessary to conduct new well-designed randomized clinical trials with appropriate methodologies., (© 2023. The Author(s).)

Background: Cervical cancer (CC), colorectal cancer (CRC), and breast cancer (BC) are diseases that can be prevented/detected through early test. Through educational programs, individuals can become better informed about these cancers and understand the importance of screening and early detection. However, many people, especially low-income, low-educated, uninsured minority population groups, do not have their cancer screenings at the recommended intervals and do not receive appropriate and timely follow-up of abnormal screening results or timely treatment after diagnosis. A community-based educational program was developed to improve knowledge and awareness toward the screening of the three cancer types in a South Texas underserved population., Methods: Residents living in Laredo, Texas were invited to participate in the present educational program. From January 2020 to April 2021, participants were recruited using social media and flyer distributions in the general community. Participants received a free live web cancer education presentation delivered by bilingual community health educators, and online pre- and post-education surveys for CC, CRC, and BC separately. Pre-post changes in knowledge for individual items were compared using McNemar's chi-squared tests., Results: Overall, the participants showed increases in CC (n = 237), CRC (n = 59), and BC (n = 56) screening knowledge and awareness after receiving the cancer screening education (Ps < 0.05). After receiving the cancer screening education, 85-97% of participants had an intent to talk to a healthcare provider about CC/CRC/BC screening, 88-97% had an intent to get a CC/CRC/BC screening test in the next 12 months or at the next routine appointment, and 90-97% had an intent to talk about CC/CRC/BC with their family members or friends., Conclusions: A community-based educational program culturally and linguistically tailored help increase knowledge and awareness about cervical, colorectal, and breast cancer screening, and promote positive changes in population's knowledge and awareness about the benefits of cancer screening. Future cancer screening educational programs in similar populations are warranted to reduce the risk of cervical, colorectal, and breast cancer., (© 2023. The Author(s).)

Objectives: Built on the Positive Youth Development (PYD) framework, this study examined how physical activity affected the subjective well-being of adolescents in the multi-ethnic area of southwest China. The mediating role of school connectedness as an external development asset and the moderating role of resilience as an internal development asset were specified and tested within the framework of sport-based PYD., Methods: A cross-sectional survey of 3143 adolescents (47.2% boys with mean age = 12.88 and SD = 1.68) was conducted in 2020. A structural equation model (SEM) was developed to estimate the direct effect of physical activity, the mediating effect of school connectedness, and the moderating effect of resilience on adolescents' subjective well-being. Multi-group comparison was made to investigate differences and similarities across three parental absence subgroups: (1) both parents present, (2) one parent absent, and (3) both parents absent., Results: As surmised, physical activity, school connectedness, and resilience all positively and significantly affected adolescents' subjective well-being. SEM analyses revealed that school connectedness mediated the effect of physical activity on subjective well-being. Moreover, resilience moderated both the direct and indirect effects of physical activity (through school connectedness) on subjective well-being. Finally, the multi-group comparison revealed a moderating effect of parental absence on the moderated mediation model., Limitations: This study is a cross-sectional survey, so inference of causal associations among the study variables is impossible., Conclusions: Healthy lifestyle behaviors, school-supportive settings, and positive individual development assets can enhance the subjective well-being of adolescents in southwest China, especially those whose parents were absent. Physical activity interventions informed by the PYD framework should be incorporated into public health programs designed to foster the physical and mental health of left-behind adolescents in southwest China., (© 2023. The Author(s).)

Transnational public and global health programs in China have rapidly expanded over the past 20 years, and have potential to make important contributions to China's global health workforce. However, there has been sparse if any literature specific to transnational public and global health higher education in China. In response, this perspective article aims to: (1) outline current transnational public and global health programs in China, and (2) delineate opportunities and challenges for transnational public and global health programs to enhance China's global health workforce. Based on internet searches, eight active transnational public and global health programs in China were identified in September 2022 (one Bachelors; four Masters; three doctorate). Degree awarding institutions are located in Australia, Portugal, the United Kingdom, and the United States. Courses for stand-alone transnational programs were co-delivered by faculty from the Chinese and foreign sponsoring institutions. The earliest and latest programs were respectively established in 2001 and 2022, and the average year of establishment was 2013. The endurance of some programs (three programs operating ≥ 10 years) indicates the potential sustainability of transnational public and global health programs in China. However, opportunities for cross-cultural engagement appear to be constrained by lack of English (or other language) requirements in some programs, limited recruitment of international students, pandemic travel restrictions, and a dearth of funding for global health research outside China. In addition, students enrolled at transnational universities in China are currently ineligible for China Scholarship Council funding. As China's need for global health capacity grows amid a rapidly shrinking population of younger citizens, strategic investments in transnational public and global health programs may be of increasing value., (© 2023. The Author(s).)