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The aim of this study was to identify psychosocial factors associated with, and predictive of, diabetes self-efficacy (DSE) in young adults with youth-onset type 2 diabetes (T2D), a vulnerable, understudied group. In this observational, longitudinal study (T1 = baseline, T2 = 1 year later), 348 participants in the TODAY2 multi-center study of youth-onset T2D, completed valid measures of: diabetes self-efficacy, beliefs about medicines, depression and anxiety symptoms, diabetes distress, attitudes, self-management support, and need insecurities. Multivariable logistic regression models evaluated independent associations of each psychosocial factor with the likelihood of being in the high/low DSE tertile groups. Multivariable linear regression models assessed associations with DSE as a continuous variable. Participants' mean age was 26 years, 67.9% were women, mean diabetes duration was 12.4 years, with mean of 2.5 diabetes-related complications. Greater self-care support increased the odds of high DSE at T2. Beliefs that medicines are overused, moderate-to-severe depressive or anxiety symptoms, and unmet material needs, decreased the odds of high DSE at T2. More support, fewer depressive and anxiety symptoms, and fewer unmet material needs at T1 predicted T2 DSE scores. Cognitions (beliefs that medicines are overused), emotions (depressive/anxiety symptoms), and social factors (self-management support, unmet material needs), were significant longitudinal predictors of DSE in young adults with youth-onset T2D. These potentially modifiable factors should be considered when screening for, and designing, interventions to enhance DSE, to improve health behaviors and forestall the development of complications in this at-risk group., Competing Interests: Declarations. Ethical approval: All procedures performed in this study were in accordance with the ethical standards of the 1964 Helsinki Declaration and its later amendments. TODAY, TODAY2 and iCount were approved by institutional review boards at 15 participating centers (IRB approval #1032847 at the primary institution). Consent to participate: Informed consent was obtained from all participants in the study. The study involved independent data collection and access to data from the TODAY2 assessments, defined during the informed consent process, and detailed in a signed informed consent document. Consent for publication: Not applicable. Competing interests: Dr Trief reports grants from National Institutes of Health during the conduct of the study, and serves on the Editorial Board of the Journal of Behavioral Medicine. Dr. Anderson reports grants from National Institutes of Health and the Leona M. and Harry B. Helmsley Charitable Trust during the conduct of the study. Dr. Weinstock reports participation in multicenter clinical trials through her institution, sponsored by: Eli Lilly, Insulet, Tandem, Amgen, Diasome, and MannKind. Ms. Wen, Mr. Burke and Ms. Bulger have nothing to disclose., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In the United States (U.S.), 90% of annual health care expenditures are devoted to people with chronic physical and mental health conditions. For people with HIV (PWH), two common, chronic comorbidities are pain and depression. This report assesses the impact of a brief psychotherapy intervention for PWH and comorbid chronic pain and depression on health care service utilization. Data from the HIV Pain and Sadness Study (HIV-PASS) randomized trial were used. Electronic health records were reviewed to tabulate use of the following services: (a) outpatient rehabilitation; (b) outpatient psychiatric; and (c) hospital-based (e.g., emergency department). Estimated average marginal effects were analyzed to determine how many times a participant accessed the service and the charge at each event. The sample consisted of 187 adults recruited from three U.S. sites. Individuals randomized to the three-month, seven session HIV-PASS intervention had average charges for hospital-based services that were significantly less during the post-treatment phase (months 4-12; 95%CI: -$16,612, -$131; p =.046) than those randomized to the comparison condition. On average, comparison condition participants were charged $8,371 more for hospital services in the 8-month period following intervention. No significant differences between treatment conditions were observed in use of outpatient rehabilitation, outpatient psychiatric services, or hospital-based care. Consistent with predictions, lower health care charges among those randomized to the HIV-PASS behavioral intervention were incurred for hospital services, indicating that a brief behavioral intervention could lead to decreased use of more emergent and expensive care services among persons with HIV, depression, and chronic pain., Competing Interests: Declarations. Conflict of Interest: Dr. Uebelacker’s spouse is employed by Abbvie Pharmaceuticals. Dr. Weisberg is the Chief Clinical Officer for RealizedCare. RealizedCare makes virtual reality-based behavioral health interventions for common problems including pain and depression. The authors declare no other relevant financial or non-financial interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In the United States (US), sexuality-based stigma continues to undermine HIV prevention and care efforts. We assessed sexual behavior stigma burden across family, healthcare, and social domains and determined associations with HIV-related outcomes among cisgender gay, bisexual, and other men who have sex with men (MSM) in nine US metropolitan statistical areas. MSM ( N = 4,086) recruited at places of MSM social congregation via venue-based, time-sampling procedures completed a survey on sexual behavior stigma, PrEP (pre-exposure prophylaxis) continuum and HIV care continuum outcomes, sociodemographic characteristics, and other measures. We calculated prevalence and overall mean stigma subscale scores (range: 0.00-1.00) and used logistic and mixed effects logistic regression to determine stigma-HIV outcome associations. Most participants identified as gay, were employed, and were from West Coast cities; roughly 40% were non-Hispanic white, aged 25 to 34 years, and had completed some college. One in five were living with HIV. Family stigma (prevalence = 47.5%; mean = 0.36) was associated with greater odds of healthcare engagement, PrEP awareness, and PrEP use among HIV-negative MSM. Anticipated healthcare stigma (prevalence = 14.5%; mean = 0.11) was associated with lower odds of healthcare engagement, current ART (antiretroviral therapy) use, and viral load undetectability among MSM living with HIV. General social stigma (prevalence = 49.9%; mean = 0.20) was associated with greater odds of PrEP awareness and use among HIV-negative MSM and lower odds of current ART use among MSM living with HIV. Targeted stigma-mitigation in family, healthcare, and other social contexts remains paramount to ending the HIV epidemic in the US., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to report.

Lysosomal storage diseases (LSDs) comprise ~50 monogenic disorders marked by the buildup of cellular material in lysosomes, yet systematic global molecular phenotyping of proteins and lipids is lacking. We present a nanoflow-based multiomic single-shot technology (nMOST) workflow that quantifies HeLa cell proteomes and lipidomes from over two dozen LSD mutants. Global cross-correlation analysis between lipids and proteins identified autophagy defects, notably the accumulation of ferritinophagy substrates and receptors, especially in NPC1 -/- and NPC2 -/- mutants, where lysosomes accumulate cholesterol. Autophagic and endocytic cargo delivery failures correlated with elevated lysophosphatidylcholine species and multilamellar structures visualized by cryo-electron tomography. Loss of mitochondrial cristae, MICOS complex components, and OXPHOS components rich in iron-sulfur cluster proteins in NPC2 -/- cells was largely alleviated when iron was provided through the transferrin system. This study reveals how lysosomal dysfunction affects mitochondrial homeostasis and underscores nMOST as a valuable discovery tool for identifying molecular phenotypes across LSDs.

Background: The effect of the anticoagulant, dabigatran, and its antagonist, idarucizumab, on coagulation remains poorly quantified. There are few pharmacokinetic-pharmacodynamic data available to determine dabigatran dose in humans or animals undergoing cardiopulmonary bypass., Methods: Five sheep were given intravenous dabigatran 4 mg/kg. Blood samples were collected for thromboelastometric reaction time (R-time) and drug assay at 5, 15, 30, 60, 120, 240, 480 min, and 24 h. Plasma dabigatran concentrations and R-times were analyzed using an integrated pharmacokinetic-pharmacodynamic model using non-linear mixed effects. The impact of idarucizumab 15 mg/kg administered 120 min after dabigatran 4 mg/kg and its effect on R-time was observed., Results: A 2-compartment model described dabigatran pharmacokinetics with a clearance (CL 0.0453 L/min/70 kg), intercompartment clearance (Q 0.268 L/min/70 kg), central volume of distribution (V1 2.94 L/70 kg), peripheral volume of distribution (V2 9.51 L/70 kg). The effect compartment model estimates for a sigmoid E MAX model using Reaction time had an effect site concentration (Ce 50 64.2 mg/L) eliciting half of the maximal effect (E MAX 180 min). The plasma-effect compartment equilibration half time (T 1/2 keo) was 1.04 min. Idarucizumab 15 mg/kg reduced R-time by approximately 5 min., Conclusions: Dabigatran reversibly binds to the active site on the thrombin molecule, preventing activation of coagulation factors. The pharmacologic target concentration strategy uses pharmacokinetic-pharmacodynamic information to inform dose. A loading dose of dabigatran 0.25 mg/kg followed by a maintenance infusion of dabigatran 0.0175 mg/kg/min for 30 min and a subsequent infusion dabigatran 0.0075 mg/kg/min achieves a steady state target concentration of 5 mg/L in a sheep model., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.