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Mitochondrial Haplogroups and Left Ventricular Diastolic Dysfunction in People Living with and without HIV
No full textCardiac dysfunction is more common in people with HIV (PWH) than those without HIV (PWoH), with mitochondrial dysfunction implicated in pathogenesis. We investigated whether variations in mitochondrial DNA (mtDNA) and certain dideoxynucleoside analogues (D-drugs) relate to left ventricular diastolic dysfunction (LVDD) in PWH.
We included individuals with echocardiograms from the Multicenter AIDS Cohort Study and Women's Interagency HIV Study. LVDD was defined using Characterizing Heart Function on Antiretroviral Therapy criteria. mtDNA haplogroups were inferred using HaploGrep. Separate exploratory multivariable logistic regressions examined associations between LVDD and African (L0L1, L2, L3 or "other") or European haplogroups (UK, H, JT, or "other"), D-drugs, and their interactions. No adjustments were made for multiple comparisons.
Among 842 men (455 PWH, 387 PWoH) and 898 women (620 PWH, 278 PWoH), LVDD prevalence was 29% in women and 24% in men. Among non-Hispanic White men with HIV, European haplogroup H was associated with lower odds of LVDD (odds ratio [OR], 0.50; 95% CI, 0.26-0.93), while haplogroup clade JT was associated with increased odds (OR, 2.09; 95% CI, 1.00-4.36). In men with HIV, D-drug exposure was associated with increased odds of LVDD (OR, 1.94; 95% CI, 1.21-3.13). No significant associations were observed between haplogroups and LVDD in women. HIV serostatus modified the association of haplogroup L2 (pinteraction=0.036) and L3 (pinteraction=0.045) with LVDD in women.
Mitochondrial genetic variation and D-drug use were associated with altered LVDD risk in men with HIV, highlighting potential biological mechanisms that may be targeted for surveillance or therapeutic strategies
The role of short-chain fatty acids in spinal cord injury: A systematic review of human and animal evidence
No full textSpinal cord injury (SCI) disrupts gut microbiota composition, resulting in dysbiosis that can worsen neuroinflammation and impede post-injury recovery. Short-chain fatty acids (SCFA), metabolites produced by the gut microbiome with anti-inflammatory properties, offer a promising avenue for improving recovery and rehabilitation outcomes.We aimed to compile a summary of the human and animal evidence on the potential benefits of SCFA or SCFA - producing bacteria in individuals with SCI.Three databases (EMBASE, Medline (Ovid) and Web of Science) were searched from inception until 19 October 2023. No language restrictions were applied. Title and abstract screening, data extraction and risk of bias assessments were done independently by two reviewers.A total of 2492 studies were retrieved, 69 full-text studies were reviewed, and 13 studies were included (11 animal and 2 human). Human studies, which involved participants with chronic SCI, linked gut dysbiosis (a proxy for low SCFA production) and human metabolic profiles, suggesting a potential role for microbiome-targeted interventions even in later stages of injury. Evidence from animal studies, predominantly in acute and sub-acute models of SCI, consistently associated SCFA interventions with improved motor function, reduced tissue damage and favorable changes in inflammatory and oxidative stress markers. Fecal microbiota transplantation and probiotics improved motor function and reduced lesion size in animal models. Gut microbiome modulations through treatments such as melatonin, moxibustion, and intermittent fasting was correlated with improved motor outcomes and increased abundance of SCFA-producing bacteria.This review highlights the potential of targeting the gut microbiota and SCFAs as therapeutic strategies for SCI recovery. However, despite promising results in animal models, human evidence remains limited
A Retrospective Analysis of Patient-Level and Neighborhood-Level Barriers in Patients Undergoing CSF Leak Repair
No full textFamily‐Based Treatment + Unified Protocol for Avoidant/Restrictive Food Intake Disorder: An Exploratory Feasibility and Treatment Response Study in a Case Series of Adolescents
No full textAdolescents with ARFID commonly seek treatment for eating difficulties as well as cooccurring emotional concerns The study demonstrates initial evidence for FBT + UP‐A as a flexible treatment for adolescent ARFID and cooccurring emotional concerns A larger controlled study is needed to establish the effectiveness of FBT + UP‐A for adolescent ARFID
Modeling the evolutionary dynamics of clonal hematopoiesis
No full textClonal hematopoiesis (CH) results from the acquisition and expansion of somatic mutations in hematopoietic stem and progenitor cells and is associated with age-related clinical sequelae, including an increased risk for cardiovascular disease, myeloid neoplasms and complications related to cancer therapy. Chemotherapy and radiation can accelerate CH expansion and further elevate the risk of adverse events, including cardiotoxicity and therapy-related myeloid neoplasms. Although CH is increasingly recognized as a clinically relevant precursor state and predictive biomarker, the long-term dynamics of CH expansion in humans remain poorly understood. Longitudinal data are often collected but not integrated with mathematical prediction. Mathematical modeling is essential for characterizing CH evolution, estimating clone fitness, inferring stem cell pool dynamics and enabling patient-level predictions. This study summarizes the current evidence on CH dynamics in humans, compares mathematical models used to predict CH progression, assesses the validity of model assumptions and discusses the implications for clinical management of individuals with these precursor conditions
Taking measurement-based care to school: Evaluating teacher-report versions of the behavior and feelings survey and the top problems assessment
No full textThere is a need for free, brief, psychometrically sound measures to support youth measurement-based care across settings. Two instruments, the standardized Behavior and Feelings Survey (BFS) and the idiographic Top Problems Assessment (TPA), have shown evidence of validity, reliability, and sensitivity to change by parent and youth report. Extending this measurement suite, we examined the psychometric properties of new teacher-report versions of the BFS and TPA. Participants were 110 youths (ages 7-13, 41.6% female) referred for school-based therapy for internalizing and/or externalizing problems. Multiinformant BFS and TPA measures were administered at pre- and posttreatment and repeatedly throughout treatment. Analyses evaluated the teacher-reported BFS-T and TPA-T across informants (relative to the parallel parent and youth versions), within-informant (relative to the Teacher Report Form), and longitudinally throughout treatment. Results showed that the BFS-T scale scores (internalizing, externalizing, and total) had good internal consistency and distributions comparable to parent/youth data. Factor analyses supported the BFS's original correlated two-factor structure with minor informant-specific modifications that do not impact scoring or interpretation. The BFS-T and TPA-T showed evidence of convergent and discriminant validity with other multiinformant measures. Longitudinal multilevel models documented sensitivity to change via negative loglinear slopes (
s < .005). Mean teacher-report trajectories resembled parent- and youth-report trajectories, but cross-informant correlations were mostly not significant, suggesting incremental utility of teacher report. The BFS and TPA are free, brief, incrementally useful, and psychometrically sound tools for measurement-based care in youth therapy-now including teacher-report forms to complement the original parent- and youth-report forms. (PsycInfo Database Record (c) 2026 APA, all rights reserved)
A new 3-D P-wave velocity model for Central America using the TeletomoDD method
No full textCentral America's tectonic complexity arises from the interaction of multiple plates and diverse plate boundaries, resulting in high seismic activity and intricate subduction processes. 3-D seismic velocity models can provide critical constraints on subduction processes and associated earthquake hazard models. Although regional tomographic studies have offered insights into seismic activity and lithospheric processes in Central America, there have been few studies that image the entire region in a consistent manner, likely due to the geological complexity and numerical challenges. In this study, we develop a new high-resolution 3-D compressional (P)-wave velocity model to investigate the subduction dynamics of the region. We apply the teletomoDD method, which uses both local and global body-wave arrivals to resolve velocity structures. We use the International Seismological Center's EHB catalogue to extract data from 6026 regional earthquakes from 1965 to 2019, recorded by seismic stations both inside and outside of our study area. Our model is further constrained by incorporating about 30 000 global events recorded by the seismic stations within our study area. We perform both checkerboard and restoration tests to assess the resolution of the model and find that the main features are resolved robustly regardless of the initial models. The model shows a coherent high-velocity anomalies along the Middle America Trench at 50 km depth, suggesting cold, dense subducting slabs. It also captures notable variations in slab geometry, including a slab window in the southern Cocos region starting at 75 km depth. Low-velocity anomalies beneath major volcanic systems such as the Central American Volcanic Arc and the Trans-Mexican Volcanic Belt point to slab dehydration, fluid migration and partial melting processes, whereas the discontinuous distribution of volcanism in Mexico and Central America appears to be influenced by the subduction of the Cocos Plate. Additionally, we identify high-velocity anomalies near the Siqueiros and Clipperton Transform Faults on the East Pacific Rise, possibly caused by mafic magmatic cumulates. The high-velocity anomaly near Swan Islands Transform Fault may reflect locally increased density inferred from previous gravity studies. Our new velocity model offers a consistent seismic structural foundation for further investigations into seismogenic processes, slab geodynamics, petrology and rheology in Central America
Racial Differences in Self-Reported Sleep Continuity Disturbance, Problem Endorsement, and Daytime Dysfunction Among Black and White Non-Hispanic Adults in the United States
No full textFew studies have assessed sleep across all sleep continuity variables (eg, sleep latency [SL], number of awakenings [NWAK], wake after sleep onset [WASO], early morning awakenings [EMA], total sleep time [TST], total wake time [TWT]) concurrently, at the community level, leading to gaps in understanding racial sleep disparities. Moreover, many studies do not examine sleep-related problem endorsement and daytime function.
To examine race differences in insomnia symptom severity (eg, sleep continuity disturbance [SCD]), problem endorsement, and daytime dysfunction among Black and White non-Hispanic adults.
Participants (N=8172) living in Greater Philadelphia completed an online community survey about their sleep between 2011 and 2021. Chi-square and
-test analyses were used to compare sleep-related differences by race. Multiple regression analyses were conducted to investigate the effect of race on sleep, controlling for age, sex, BMI, and education.
Black non-Hispanics had significantly worse SL (Δ>3 min), WASO (Δ>8.4 min), and TWT (Δ >12.1 min) but not NWAK (Δ36.8 min). Appreciable effect sizes ranged from .01 to .44. White non-Hispanics consistently endorsed greater daytime dysfunction with small effects ranging from .07 to .14.
Findings suggest that Black non-Hispanics experience less restorative sleep, which can lead to impaired cognitive function, mood disturbances, and increased risk of chronic illness. Observed differences in TST may be due to the unmeasured effects of EMA or to reduced time in bed, underscoring the importance of comprehensive approaches to understanding sleep disturbances like insomnia. Addressing insomnia severity using multidimensional approaches and with targeted interventions, such as Cognitive Behavioral Therapy for Insomnia and/or systematic sleep extension, could help improve sleep health. Moreover, examining differences in sleep across sociodemographic characteristics leads to nuanced understandings that highlight the importance of developing targeted, precision-based behavioral health interventions
Prediction Analysis of Microarray of 50 genes (PAM50) classifier validated for predicting prostate cancer progression in active surveillance: Miami Active Surveillance Trial (MAST)
No full textTo evaluate basal-luminal cell of origin subtyping using Prediction Analysis of Microarray of 50 genes (PAM50) genomic classification profiles for predicting disease progression in men undergoing active surveillance (AS) for prostate cancer (PCa).
In the prospective Miami Active Surveillance Trial (MAST) trial, 205 men undergoing AS received serial multiparametric magnetic resonance imaging (MRI) and biopsies, including MRI-targeted and systematic sampling. The highest-grade core from each biopsy was sent for expression profiling using Decipher, a clinical-grade transcriptome assay (Veracyte Inc., San Diego, CA, USA). Basal-luminal subtyping was evaluated using PAM50 molecular subtype models. PCa grade progression was compared across subtypes, as were gene mutation signatures, prognostic indices, and pathway activities. Kaplan-Meier curves, log-rank test, and multivariable Cox regression were used to assess association between PAM50 and grade progression. Heatmaps and volcano plots were rendered to illustrate potential mechanistical differences between PAM50 subtypes.
Of the 205 patients, 128 had transcriptome data for baseline basal-luminal classification. PAM50 identified 46 Luminal A (LA), 26 Luminal B (LB), and 56 Basal subtypes. Decipher scores were lowest in LA, followed by Basal, and highest in LB. Grade progression-free survival was worse in patients with the LB subtype (median 1.7 years) compared to those with LA and Basal subtypes (median 2.9 years; log-rank P = 0.005); LB patients had grade progression-free survival of 34% by 24 months of AS, compared to 63% for Basal or 68% for LA. Transcriptome analysis showed distinct enrichment profiles for each subtype, with LB strongly associated with SPOP and CHD1 mutations. Limitations include small sample size and single-institution setting.
The PAM50 basal-luminal subtyping shows promise as a molecular classification tool for predicting progression risk in PCa. This is one of the only prospective studies evaluating PAM50 subtyping for predicting cancer progression in a cohort of men undergoing AS for PCa