Associations Between Neighborhood Racialized Economic Segregation with Cardiometabolic Health and Cortisol in a Racially/Ethnically Diverse Sample of Children from Minneapolis-St. Paul.

Introduction: Past research shows that structural racism contributes to disparities in cardiometabolic health among racially/ethnically minoritized populations. Methods: This cross-sectional study examined the correlation between census tract-level racialized economic segregation and child health metrics among a racially and ethnically diverse cohort of 350 children (ages 6.5-13.8) from Minneapolis-St. Paul, MN. Results: A consistent cardiometabolic and cortisol outcome gradient was observed across the index of concentration at the extremes tertiles, such that health risk factors increased as tract privilege decreased. Conclusion: Racialized economic segregation was associated with less favorable child health outcomes, underscoring the potential importance of place-based interventions for promoting children's health.

Lessons from a decade of adult vaccine rollout in low- and middle-income countries: a scoping review.

INTRODUCTION: The historical focus of vaccines on child health coupled with the advent of novel vaccines targeting adult populations necessitates exploring strategies for adult vaccine implementation. AREAS COVERED: This scoping review extracts insights from the past decade's experiences introducing adult vaccines in low- and middle-income countries. Among 25 papers reviewed, 19 focused on oral cholera vaccine, 2 on Meningococcal A vaccines, 2 on tetanus toxoid vaccine, 1 on typhoid vaccine, and 1 on Ebola vaccine. Aligned with WHO's Global Framework for New TB Vaccines for Adults and Adolescents, our findings center on vaccine availability, accessibility, and acceptance. EXPERT OPINION: Availability findings underscore the importance of understanding disease burden for prioritization, multi-sectoral collaboration during planning, and strategic resource allocation and coordination. Accessibility results highlight the benefits of leveraging existing health infrastructure and adequately training healthcare workers, and contextually tailoring vaccine delivery approaches to reach challenging sub-groups like working male adults. Central to fostering acceptance, resonant sensitization, and communication campaigns engaging the communities and utilizing trusted local leaders countered rumors and increased awareness and uptake. As we approach the introduction of a new adult TB vaccine, insights from this review equips decision-makers with key evidence-based recommendations to support successful and equitable vaccinations targeting adults.

Kinetic Modeling for BT200 to Predict the Level of Plasma-Derived Coagulation Factor VIII in Humans.

Lack of Factor VIII (FVIII) concentrates is one of limiting factors for Hemophilia A prophylaxis in resource-limited countries. Rondaptivon pegol (BT200) is a pegylated aptamer and has been shown to elevate the level of von Willebrand Factor (VWF) and FVIII in previous studies. A population pharmacokinetic model for BT200 was built and linked to the kinetic models of VWF and FVIII based on reasonable assumptions. The developed PK/PD model for BT200 described the observed kinetic of BT200, VWF, and FVIII in healthy volunteers and patients with mild-to-moderate hemophilia A from two clinical trials. The developed model was evaluated using an external dataset in patients with severe hemophilia A taking recombinant FVIII products. The developed and evaluated PK/PD model was able to describe and predict concentration-time profiles of BT200, VWF, and FVIII in healthy volunteers and patients with hemophilia A. Concentration-time profiles of FVIII were then predicted following coadministration of plasma-derived FVIII concentrate and BT200 under various dosing scenarios in virtual patients with severe hemophilia A. Plasma-derived products, that contain VWF, are more accessible in low-resource countries as compared to their recombinant counterparts. The predicted time above 1 and 3 IU/dL FVIII in one week was compared between scenarios in the absence and presence of BT200. A combination dose of 6 mg BT200 once weekly plus 10 IU/kg plasma-derived FVIII twice weekly maintained similar coverage to a 30 IU/kg FVIII thrice weekly dose in absence of BT200, representing only 22% of the FVIII dose per week.

Identifying factors and causal chains associated with optimal implementation of Lynch syndrome tumor screening: An application of coincidence analysis.

PURPOSE: This study compared Lynch syndrome universal tumor screening (UTS) across multiple health systems (some of which had two or more distinct UTS programs) to understand multi-level factors that may impact the successful implementation of complex programs. METHODS: Data from 66 stakeholder interviews were used to conduct multi-value coincidence analysis (mv-CNA) and identify key factors that consistently make a difference in whether UTS programs were implemented and optimized at the system level. RESULTS: The selected CNA model revealed combinations of conditions that distinguish 4 optimized UTS programs, 10 non-optimized programs, and 4 systems with no program. Fully optimized UTS programs had both a maintenance champion and a positive inner setting. Two independent paths were unique to non-optimized programs: 1) positive attitudes and a mixed inner setting, or 2) limited planning & engaging among stakeholders. Negative views about UTS evidence or lack of knowledge about UTS led to a lack of planning and engaging, which subsequently prevented program implementation. CONCLUSION: The model improved our understanding of program implementation in health care systems and informed the creation of a toolkit to guide UTS implementation, optimization, and changes. Our findings and toolkit may serve as a use case to increase the successful implementation of other complex precision health programs.

Images in Anesthesiology: Carotid Sinus Reflex From Neck Mass and Opioids.

Surgery on head and neck masses presents unique challenges to overcome, especially in relation to preoperative anesthesia induction. Tumor proximity to the carotid sinus can result in extreme hemodynamic depression, by way of compression or direct invasion of the node. Neck hyperextension required for endotracheal intubation can worsen the underlying compression. Additionally, many anesthetic agents have sympatholytic properties that can exacerbate this imbalance further toward the parasympathetic response. We present a case of a patient with non-Hodgkin lymphoma whose tumor compression of the carotid sinus precipitated an exaggerated vagal reflex response following fentanyl administration.

Erratum: Hematologic DNMT3A reduction and high-fat diet synergize to promote weight gain and tissue inflammation.

[This corrects the article DOI: 10.1016/j.isci.2024.109122.].

Recommendations for Recovery of the COVID-19 Pandemic-related Diagnostic, Screening, and Procedure Backlog in Ontario: A Survey of Healthcare Leaders.

PURPOSE: The COVID-19 pandemic has resulted in a significant diagnostic, screening, and procedure backlog in Ontario. Engagement of key stakeholders in healthcare leadership positions is urgently needed to inform a comprehensive provincial recovery strategy. METHODS: A list of 20 policy recommendations addressing the diagnostic, screening and procedure backlog in Ontario were transformed into a national online survey. Policy recommendations were rated on a 7-point Likert scale (strongly agree to strongly disagree) and organized into those retained (≥75% strongly agree to somewhat agree), discarded (≥80% somewhat disagree to strongly disagree), and no consensus reached. Survey participants included a diverse sample of healthcare leaders with the potential to impact policy reform. RESULTS: Of 56 healthcare leaders invited to participate, there were 34 unique responses (61% response rate). Participants were from diverse clinical backgrounds, including surgical subspecialties, medicine, nursing, and healthcare administration and held institutional or provincial leadership positions. A total of 11 of 20 policy recommendations reached the threshold for consensus agreement with the remaining 9 having no consensus reached. CONCLUSION: Consensus agreement was reached among Canadian healthcare leaders on 11 policy recommendations to address the diagnostic, screening, and procedure backlog in Ontario. Recommendations included strategies to address patient information needs on expected wait times, expand health and human resource capacity, and streamline efficiencies to increase operating room output. No consensus was reached on the optimal funding strategy within the public system in Ontario or the appropriateness of implementing private funding models.

Genotypic variation in the promoter region of the CRH-248 gene interacts with early rearing experiences to disrupt the development of the HPA axis in infant rhesus macaques (Macaca mulatta).

Aberrant functioning of the hypothalamic-pituitary-adrenal (HPA) axis is a hallmark of conditions such as depression, anxiety disorders, and post-traumatic stress disorder. Early-life adversity and genetic variation can interaction to disrupt HPA axis regulation, potentially contributing to certain forms of psychopathology. This study employs a rhesus macaque model to investigate how early parental neglect interacts with a single nucleotide polymorphism within the promoter region of the corticotropin-releasing hormone (CRH-248) gene, impacting the development of the HPA axis. For the initial six months of life, 307 rhesus monkey infants (n = 146 females, n = 161 males) were either reared with their mothers (MR) in conditions emulating the natural environment (control group) or raised without maternal care in groups with constant or 3-hours daily access to same-aged peers (NR). Blood samples collected on days 30, 60, 90, and 120 of life under stressful conditions were assayed for plasma cortisol and adrenocorticotropic hormone (ACTH) concentrations. Findings revealed that NR subjects exhibited a significant blunting of both ACTH and cortisol concentrations. Notably, there was a gene-by-environment interaction observed for ACTH and cortisol levels, with NR subjects with the polymorphism displaying higher ACTH concentrations and lower cortisol concentrations. To the extent that these results generalize to humans, they suggest that early parental neglect may render individuals vulnerable to HPA axis dysfunction, a susceptibility that is modulated by CRH-248 genotype-a gene-by-environment interaction that leaves a lasting developmental signature.

Bring It Up: An Adapted Collaborative Care Model for Depression in a Safety-Net Primary Care Clinic.

Objective: Over 90 clinical trials demonstrate the efficacy of the collaborative care model (CoCM) to treat depression in primary care but there is significant variability in real-world CoCM implementation and scalability. This study aimed to determine the feasibility and effectiveness of an adapted CoCM in a safety-net primary care setting. Methods: Bring It Up! (BIU) is a pilot trial comparing an adapted CoCM (intervention group) to usual care (historical controls) for primary care safety-net clinic patients with depression. Inclusion criteria: (1) age ≥18; (2) Patient Health Questionnaire-9 (PHQ-9) score ≥10; and (3) major depressive disorder diagnosis. Patients who completed ≥6 months of treatment upon rolling enrollment (April 1, 2018-October 31, 2019) were included. Historical controls completed ≥6 months of usual care in 2017. BIU included all aspects of CoCM except accountable care and leveraged existing staff rather than a dedicated care manager. The primary outcome was depression remission (PHQ-9 <5) within 6 months. Secondary outcomes included depression response, adherence to treatment guidelines and care coordination process. Data were extracted from the electronic health record. Results: Thirty-six patients received the intervention; 41 controls received usual care. Depression remission was achieved in 33.3% of intervention patients and 0% of controls (p = 0.001). Of intervention patients, 44.4% achieved ≥50% reduction in PHQ-9 compared to 4.9% of controls (p = 0.003). Further, 66.7% of intervention patients had guideline-recommended antidepressant medication titration compared to 26.9% of controls (p = 0.003); 94.4% of intervention patients had PHQ-9 repeated compared to 53.7% of controls (p < 0.001). Conclusions: An adapted CoCM was feasible and improved depression care in a safety-net clinic.

Beyond Victim Identification: A Practitioner's Guide to Designing a Youth Anti-Sex Trafficking Advocacy Program.

Thousands of youth are sexually trafficked each year in the United States. In order to address this concern, anti-trafficking advocates often emphasize the importance of uniform screening protocols to assist with the identification of survivors. Unfortunately, an oft-overlooked component of sex trafficking identification is what to do once a victim has been identified, and how to best meet survivors' complex needs. In this article, the authors provide social work practitioners and other advocates with best practice guidelines for how to design and evaluate anti-sex trafficking advocacy programs for children and youth. These guidelines include considerations related to direct services with clients, community partnerships, and organizational capacity, as well as recommendations for how to begin and then evaluate programming. Regardless of the form selected for the program, all anti-sex trafficking programs should be designed to provide effective, client-centered follow-up and advocacy once a positive identification is made in the community. The recommendations included in this paper are based upon extant literature, the authors' practice experience with survivors, and insights from anti-sex trafficking program evaluations.

One-Hour Suicide Prevention Training Makes a Difference!

ABSTRACT: Nurses and other healthcare workers in the United States are at increased risk of suicide compared to non-healthcare workers. College students also experience high suicide risk. To impact suicide prevention in these populations, a Question, Persuade, Refer (QPR) 1-hour gatekeeper suicide prevention training program was implemented at the University of Detroit Mercy for faculty, staff, and administrators in the College of Health Professions (N = 43). Knowledge in seven areas of suicide significantly increased after the training (p < .001). Sixteen attitudes about suicide improved; however, only two showed a statistically significant change. Results support that 1-hour QPR training can be effectively implemented in a large organization.

(S)-ML-SA1 ACTIVATES AUTOPHAGY VIA TRPML1-TFEB PATHWAY.

Autophagic flux plays a crucial role in various diseases. Recently, the lysosomal ion channel TRPML1 has emerged as a promising target in lysosomal storage diseases, such as mucolipidosis. The discovery of mucolipin synthetic agonist-1 (ML-SA1) has expanded our understanding of TRPML1's function and its potential therapeutic uses. However, ML-SA1 is a racemate with limited cellular potency and poor water solubility. In this study, we synthetized rac-ML-SA1, separated the enantiomers by chiral liquid chromatography and determined their absolute configuration by vibrational circular dichroism (VCD). In addition, we focused on investigating the impact of each enantiomer of ML-SA1 on the TRPML1-TFEB axis. Our findings revealed that (S)-ML-SA1 acts as an agonist for TRPML1 at the lysosomal membrane. This activation prompts transcription factor EB (TFEB) to translocate from the cytosol to the nucleus in a dose-dependent manner within live cells. Consequently, this signaling pathway enhances the expression of coordinated lysosomal expression and regulation (CLEAR) genes and activates autophagic flux. Our study presents evidence for the potential use of (S)-ML-SA1 in the development of new therapies for lysosomal storage diseases that target TRPML1.

Optical manipulation of the charge-density-wave state in RbV3Sb5.

Broken time-reversal symmetry in the absence of spin order indicates the presence of unusual phases such as orbital magnetism and loop currents1-4. The recently discovered kagome superconductors AV3Sb5 (where A is K, Rb or Cs)5,6 display an exotic charge-density-wave (CDW) state and have emerged as a strong candidate for materials hosting a loop current phase. The idea that the CDW breaks time-reversal symmetry7-14 is, however, being intensely debated due to conflicting experimental data15-17. Here we use laser-coupled scanning tunnelling microscopy to study RbV3Sb5. By applying linearly polarized light along high-symmetry directions, we show that the relative intensities of the CDW peaks can be reversibly switched, implying a substantial electro-striction response, indicative of strong nonlinear electron-phonon coupling. A similar CDW intensity switching is observed with perpendicular magnetic fields, which implies an unusual piezo-magnetic response that, in turn, requires time-reversal symmetry breaking. We show that the simplest CDW that satisfies these constraints is an out-of-phase combination of bond charge order and loop currents that we dub a congruent CDW flux phase. Our laser scanning tunnelling microscopy data open the door to the possibility of dynamic optical control of complex quantum phenomenon in correlated materials.

Remote Monitoring App for Endocrine Therapy Adherence Among Patients With Early-Stage Breast Cancer: A Randomized Clinical Trial.

Importance: Adjuvant endocrine therapy (AET) use among women with early-stage, hormone receptor-positive breast cancer reduces the risk of cancer recurrence, but its adverse symptoms contribute to lower adherence. Objective: To test whether remote monitoring of symptoms and treatment adherence with or without tailored text messages improves outcomes among women with breast cancer who are prescribed AET. Design, Setting, and Participants: This nonblinded, randomized clinical trial (RCT) following intention-to-treat principles included English-speaking women with early-stage breast cancer prescribed AET at a large cancer center with 14 clinics across 3 states from November 15, 2018, to June 11, 2021. All participants had a mobile device with a data plan and an email address and were asked to use an electronic pillbox to monitor AET adherence and to complete surveys at enrollment and 1 year. Interventions: Participants were randomized into 3 groups: (1) an app group, in which participants received instructions for and access to the study adherence and symptom monitoring app for 6 months; (2) an app plus feedback group, in which participants received additional weekly text messages about managing symptoms, adherence, and communication; or (3) an enhanced usual care (EUC) group. App-reported missed doses, increases in symptoms, and occurrence of severe symptoms triggered follow-ups from the oncology team. Main Outcomes and Measures: The primary outcome was 1-year, electronic pillbox-captured AET adherence. Secondary outcomes included symptom management abstracted from the medical record, as well as patient-reported health care utilization, symptom burden, quality of life, physician communication, and self-efficacy for managing symptoms. Results: Among 304 female participants randomized (app group, 98; app plus feedback group, 102; EUC group, 104), the mean (SD) age was 58.6 (10.8) years (median, 60 years; range, 31-83 years), and 60 (19.7%) had an educational level of high school diploma or less. The study completion rate was 87.5% (266 participants). There were no statistically significant differences by treatment group in AET adherence (primary outcome): 76.6% for EUC, 73.4% for the app group (difference vs EUC, -3.3%; 95% CI, -11.4% to 4.9%; P = .43), and 70.9% for the app plus feedback group (difference vs EUC, -5.7%; 95% CI, -13.8% to 2.4%; P = .17). At the 1-year follow-up, app plus feedback participants had fewer total health care encounters (adjusted difference, -1.23; 95% CI, -2.03 to -0.43; P = .003), including high-cost encounters (adjusted difference, -0.40; 95% CI, -0.67 to -0.14; P = .003), and office visits (adjusted difference, -0.82; 95% CI, -1.54 to -0.09; P = .03) over the previous 6 months compared with EUC participants. Conclusions and Relevance: This RCT found that a remote monitoring app with alerts to the patient's care team and tailored text messages to patients did not improve AET adherence among women with early-stage breast cancer; however, it reduced overall and high-cost health care encounters and office visits without affecting quality of life. Trial Registration: ClinicalTrials.gov Identifier: NCT03592771.

The Use of Impella 5.5 Reduces Pulmonary Vascular Resistance as Bridge to Heart Transplant in a Pediatric Patient.

This case report explores the successful use of the Impella 5.5 (Abiomed Inc., Danvers, MA) device in a 22 kg, 0.89 body surface area (BSA) pediatric patient with longstanding dilated cardiomyopathy and elevated pulmonary vascular resistance. The article details the device selection, management, and outcome demonstrating the feasibility and potential benefits of the Impella 5.5 as a device within the pediatric population.

Evaluation of the Analytical Performance of a Lateral Flow Assay for the Detection of Anti-Coccidioides Antibodies in Human Sera-Argentina.

Coccidiomycosis is a potentially life-threatening fungal infection endemic to certain regions of Argentina. The infection is caused by Coccidioides spp. and is primarily diagnosed by Coccidioides antibody (Ab) detection. Access to rapid, highly accurate diagnostic testing is critical to ensure prompt antifungal therapy. The sona Coccidioides Ab Lateral Flow Assay (LFA) performs faster and requires less laboratory infrastructure and equipment compared with other Ab detection assays, potentially providing a substantial improvement for rapid case screening in coccidioidomycosis-endemic regions; however, validation of this test is needed. Thus, we aimed to evaluate the analytical performance of the sona Coccidioides Ab (LFA) and compare agreement with anti-Coccidioides Ab detection assays. A total of 103 human sera specimens were tested, including 25 specimens from patients with coccidioidomycosis and 78 from patients without coccidioidomycosis. The sona Coccidioides Ab Lateral Flow Assay (LFA) was performed with a sensitivity of 88%, and specificity and accuracy of 87%. Furthermore, the Coccidioides Ab LFA had good agreement with other anti-Coccidioides Ab detection assays. Our findings suggest the sona Coccidioides Ab LFA has satisfactory performance and may be useful for diagnosing coccidioidomycosis in endemic regions.

Estimated prophylactic dose required to achieve 3% trough as a function of age and concentrate class in multi-country severe WAPPS-Hemo haemophilia patients.

INTRODUCTION: Web-Accessible Population-Pharmacokinetic Service-Haemophilia (WAPPS-Hemo) data are available to study factor-concentrate usage, defined as the required weekly dose to achieve a 3% trough (WD3T), across standard and extended half-life (SHL/EHL) products. AIM: To provide baseline usage data including (i) differences across plasma-derived (pdSHL) versus recombinant (rSHL) products, (ii) SHL versus EHL, and (iii) effect of age and positive inhibitor history. METHODS: PK profiles (n = 14,416 patients, 0.3-85.2 years) and linear mixed effects models were used to estimate usage versus age, controlling for significant factors, using 95% confidence intervals to perform comparisons across all ages and posthoc tests to assess the differences. RESULTS: Average usage was significantly higher for pdSHL versus rSHL in patients with a positive inhibitor history (PIH; 1.9-2.5 times higher), for SHL versus EHL (4-10 times), and was significantly associated with age. CONCLUSION: Baseline usage patterns from 2017 to early 2023 provide a benchmark for assessing the impact of emerging technologies in haemophilia.

Exploring the genetic control of sweat gland characteristics in beef cattle for enhanced heat tolerance.

BACKGROUND: Thermal stress in subtropical regions is a major limiting factor in beef cattle production systems with around $369 million being lost annually due to reduced performance. Heat stress causes numerous physiological and behavioral disturbances including reduced feed intake and decreased production levels. Cattle utilize various physiological mechanisms such as sweating to regulate internal heat. Variation in these traits can help identify genetic variants that control sweat gland properties and subsequently allow for genetic selection of cattle with greater thermotolerance. METHODS: This study used 2,401 Brangus cattle from two commercial ranches in Florida. Precise phenotypes that contribute to an animal's ability to manage heat stress were calculated from skin biopsies and included sweat gland area, sweat gland depth, and sweat gland length. All animals were genotyped with the Bovine GGP F250K, and BLUPF90 software was used to estimate genetic parameters and for Genome Wide Association Study. RESULTS: Sweat gland phenotypes heritability ranged from 0.17 to 0.42 indicating a moderate amount of the phenotypic variation is due to genetics, allowing producers the ability to select for favorable sweat gland properties. A weighted single-step GWAS using sliding 10 kb windows identified multiple quantitative trait loci (QTLs) explaining a significant amount of genetic variation. QTLs located on BTA7 and BTA12 explained over 1.0% of genetic variance and overlap the ADGRV1 and CCDC168 genes, respectively. The variants identified in this study are implicated in processes related to immune function and cellular proliferation which could be relevant to heat management. Breed of Origin Alleles (BOA) were predicted using local ancestry in admixed populations (LAMP-LD), allowing for identification of markers' origin from either Brahman or Angus ancestry. A BOA GWAS was performed to identify regions inherited from particular ancestral breeds that might have a significant impact on sweat gland phenotypes. CONCLUSIONS: The results of the BOA GWAS indicate that both Brahman and Angus alleles contribute positively to sweat gland traits, as evidenced by favorable marker effects observed from both genetic backgrounds. Understanding and utilizing genetic traits that confer better heat tolerance is a proactive approach to managing the impacts of climate change on livestock farming.

Investigating the shared genetic basis and causal relationships between mucosa-associated lymphoid tissue inflammation and psychiatric disorders.

Background: Chronic and acute inflammation of the mucosa-associated lymphoid tissue have been positively linked to the development of psychiatric disorders in observational studies. However, it remains unclear whether this association is causal. In the present study, we investigated this association, using as proxies genetically predicted tonsillectomy, appendectomy and appendicitis on psychiatric disorders including major depressive disorder (MDD), schizophrenia (SCZ), bipolar depression (BD) and anxiety (ANX) via a two-sample Mendelian randomization (MR) analysis. Methods: Genetic association summary statistics for tonsillectomy, appendectomy and appendicitis were sourced from FinnGen Consortium, comprising data from 342,000 participants. Genetic correlations between all exposures and outcome were calculated with Linkage Disequilibrium Score (LDSC) Regression analysis. MR estimates were then calculated to assess their impact on the risk of developing psychiatric disorders. Sensitivity analysis was employed to test for any directional pleiotropy. Results: Our results suggest that there is no direct causal association between tonsillectomy, appendectomy or appendicitis with a heightened risk for development of psychiatric disorders. The robustness of the results of the main MR analysis was further confirmed with additional sensitivity analyses. However, a moderate inverse genetic correlation was observed between tonsillectomy and MDD traits (rg=-0.39, p-value (P)=7.5x10-5). Conclusion: Our findings provide, for the first time, evidence that there is no causal association between tonsillectomy or appendectomy on subsequent vulnerability of developing psychiatric disorders. Future studies using larger sample size GWAS should focus on unraveling the confounding factors and mediators to investigate this relationship further.