Tag: nevin manimala

Aliment Pharmacol Ther. 2026 Mar 11. doi: 10.1111/apt.70596. Online ahead of print.

ABSTRACT

BACKGROUND: Metabolic dysfunction (MetD) and alcohol use disorder (AUD) frequently coexist as synergistic risk factors for steatotic liver disease. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are established therapies for MetD, including type 2 diabetes mellitus (T2DM) and obesity. Recent studies suggested potential beneficial effects of GLP-1RA to decrease addictive behaviours in AUD. We evaluated the outcomes of GLP-1RA therapy compared with FDA-approved pharmacotherapies for AUD, including naltrexone, acamprosate, and disulfiram, in patients with dual risk factors of MetD and AUD.

METHODS: We conducted a retrospective cohort study of patients at Stanford Health Care (2017-2025). Eligible patients had a concurrent diagnosis of alcohol-related complications meeting criteria for AUD and MetD, including obesity (BMI > 25) and/or a history of T2DM with HbA1c > 5.7. Those with advanced liver disease within 1 year of diagnosis were excluded. Exposure groups included ≥ 6 months of GLP-1RA therapy (semaglutide or tirzepatide) in comparison with FDA-approved pharmacotherapies for AUD. Propensity score matching was employed to reduce the effects of confounding factors.

RESULTS: In total, 1946 patients were diagnosed concurrently with AUD and MetD. Of them, 274 patients were exposed to GLP-1RA, 1272 to naltrexone, 232 to acamprosate, and 168 to disulfiram. Patients were followed for an average of 1341 days. Patients exposed to GLP-1RA had higher BMI (35.5 vs. 30.1) and more T2DM (66% vs. 14%). GLP-1RA therapy was associated with lower 1-year AUD relapse [IRR 0.55, 95% CI 0.42-0.73; p < 0.01], greater BMI reduction (-1.3 vs. -0.3; p = 0.004), and HbA1c improvement (-1.0 vs. +0.1; p = 0.02). The incidence of decompensated cirrhosis trended lower but was not statistically significant [HR 0.52, p = 0.09]. Mortality was similar.

CONCLUSIONS: GLP-1RAs are a promising option for patients with concurrent MetD and AUD, improving relapse rates and metabolic outcomes compared with currently FDA-approved pharmacotherapies for AUD. Trends toward better liver outcomes support further prospective evaluation.

PMID:41813606 | DOI:10.1111/apt.70596

Int J Cancer. 2026 Mar 11. doi: 10.1002/ijc.70412. Online ahead of print.

ABSTRACT

Multiple myeloma (MM) is the most common plasma cell dyscrasia in the United States with tremendously high burden. MM is preceded by a premalignant condition, monoclonal gammopathy of undetermined significance (MGUS). Although several risk factors for progression have been identified (e.g., older age, male sex, black race, obesity, chemical exposure), their relative contributions remain unclear. Unlike other malignancies, such evidence is lacking for MM despite its high burden. To identify potential intervention strategies that can effectively prevent progression in patients with MGUS, we quantified contributions of the identified modifiable risk factors in the United States Veteran population with MGUS. Compared to the general population, this population is particularly vulnerable to MM as its higher proportions of male and older age as well as the potential prior Agent Orange exposure. We conducted a retrospective cohort study in the Veterans Health Administration and calculated multivariable-adjusted population attributable fractions (aPAFs) of progression accounting for competing risk of death. The aPAF estimates the proportion of progression burden in the population with MGUS that is statistically attributable to a specific risk factor, independent of other factors. In the cohort of 35,073 Veterans with MGUS, among all evaluated risk factors (both modifiable and non-modifiable), excess body mass index (BMI ≥25 kg/m²) was the leading factor (Black: aPAF = 27.1%, 95% CI 19.5%-34.0%; White: 27.2%, 95% CI 20.3%-33.4%; All: aPAF = 27.1%, 95% CI 22.1%-31.9%). Our study highlights the potential of weight management and lifestyle modification for informing the design of targeted MM prevention strategies for Veterans diagnosed with MGUS.

PMID:41813601 | DOI:10.1002/ijc.70412

Alzheimers Dement. 2026 Mar;22(3):e71274. doi: 10.1002/alz.71274.

ABSTRACT

INTRODUCTION: Sleep disturbances are common and distressing for people with dementia and their family caregivers, with limited treatment options. The DREAMS START (Dementia RElAted Manual for Sleep; STrAtegies for RelaTives) multi-component intervention for sleep disturbance in people at home with dementia is clinically and cost-effective at 8 months. In this long-term follow-on study, we assessed 2-year clinical effectiveness.

METHODS: We recruited dyads of people with dementia and their family caregivers from community settings, for a two-arm, multi-center, single-blind, parallel-arm, superiority trial with the primary outcome Sleep Disorders Inventory (SDI). Analyses were intention to treat.

RESULTS: We randomized 377 dyads, 189 to treatment-as-usual (TAU) and 188 to intervention; 177 dyads (46.9%) were followed up at 24 months. Two-year adjusted mean SDI score was lower in the intervention arm than TAU (-5.40; 95% CI -9.14 to -1·67; p = 0·005).

DISCUSSION: In this follow-on study we demonstrate 2-year improvement in sleep disruption for people with dementia. DREAMS START has potential for delivery at scale.

PMID:41813600 | DOI:10.1002/alz.71274

DNA Cell Biol. 2026 Mar 11:10445498261421790. doi: 10.1177/10445498261421790. Online ahead of print.

ABSTRACT

Breast cancer is the most diagnosed cancer in women and the second leading cause of cancer-related mortality worldwide. Advances in genetic technology have highlighted the heterogeneity of breast cancer, composed of various biological subtypes, with genetic profiling playing a crucial role in predicting chemotherapy response. This underscores the importance of identifying sensitive diagnostic and prognostic markers for early detection and developing more efficient targeted therapies. Among these, survivin, a protein linked to apoptosis inhibition and cell cycle regulation, is strongly expressed in various cancers, including breast cancer, where its overexpression is associated with poor prognosis and reduced survival rates. To analyze the effects of survivin gene inhibition in a triple-negative breast cancer (TNBC) model. The MDA-MB-231 cell line was stably transfected with short hairpin RNA targeting survivin, and the inhibition was validated via RT-qPCR and Western blot. Morphological evaluation, proliferation and migration assays, and a differential gene expression analysis using the GeneChip™ Human Gene 2.0 ST Array were performed. Statistical analyses were conducted with GraphPad Prism version 8 and Transcriptome Analysis Console. Survivin-inhibited MDA-MB-231-KD cells exhibited evident morphological changes, reduced migration capacity, and altered expression of genes such as BCL2, COX1, COX2, VGF, BIR2, and CDC20, involved in key cancer signaling pathways. Inhibition of survivin in this TNBC model induces critical cellular changes and significantly alters gene expression associated with tumor progression, highlighting its potential as a therapeutic target.

PMID:41813598 | DOI:10.1177/10445498261421790

Int J Cancer. 2026 Mar 11. doi: 10.1002/ijc.70427. Online ahead of print.

ABSTRACT

Monoclonal gammopathy of undetermined significance (MGUS) is a necessary precursor condition to multiple myeloma (MM). Given the role of autophagy in modulating MM risk, we investigated whether genetic variation in autophagy-related genes influences susceptibility to MGUS. We analyzed the association of 34,042 common autophagy-related single nucleotide polymorphisms (SNPs) with MGUS across six independent cohorts, five from Europe and one from North America, comprising 2317 MGUS cases and 282,358 controls. We also assessed their impact on immune parameters, including absolute counts of 91 blood-derived immune cell subsets and 103 circulating immunological proteins. Meta-analysis revealed a genome-wide significant association between the ULK4_rs6599175C allele and increased MGUS risk (p = 3.35 × 10^-8). Carriers of this allele showed reduced counts of memory B cell subsets (IgM+CD38+CD27+ and IgD+IgM+CD27+; p = .0038 and p = .0056, respectively) and natural effector B cells (CD24+CD38+IgD+IgM+ cells; p = .0060). Although these associations were not statistically significant after multiple testing correction, they suggest a role of ULK4 in early B-cell differentiation. Additionally, the CDKN2A_rs2811710 variant showed a suggestive association with MGUS risk (p = 2.17 × 10^-4), affecting transcription factor binding involved in B-cell proliferation and differentiation, although it lacked association with immune markers. In conclusion, we confirm a genome-wide significant association of the ULK4 locus and MGUS risk, supporting its role in early B-cell differentiation, and identify CDKN2A as a candidate susceptibility locus warranting further investigation.

PMID:41813586 | DOI:10.1002/ijc.70427

Trop Med Int Health. 2026 Mar 11. doi: 10.1111/tmi.70114. Online ahead of print.

ABSTRACT

INTRODUCTION: In 1999, the prevalence of female genital mutilation (FGM) was 5% in the Democratic Republic of the Congo (DRC). This study aims to assess FGM prevalence and types, describe its demographic and sociocultural characteristics, and evaluate its long-term impact on pelvic floor and sexual function.

METHODS: A cross-sectional study was conducted from 2021 to 2023 among 519 adult women living in six provinces of the DRC, selected to represent the country’s ethnolinguistic diversity. Pregnant women, those within 6 months of childbirth, survivors of sexual violence, and those with war mutilations were excluded. A questionnaire was designed to collect data, supplemented by a vulvar assessment. The variables were compared using appropriate statistical tests (p < 0.05).

RESULTS: The prevalence of FGM was 15.2% (95% CI: 12.2%-18.6%). The prevalence of FGM Types I-II and inner labia elongation (ILE) was 1.7% (95% CI: 0.8%-3.3%) and 13.5% (95% CI: 10.7%-16.7%), respectively. ILE was on average performed at the age of 13.8 years, mainly by women themselves (88.6%), while the circumstances of FGM I-II practice were unknown. ILE was practiced among the Swahili (65.7%) and the Baluba (27.1%), while FGM I-II were practiced among the Bangala (100%). Women with ILE were at higher risk of urinary incontinence (OR: 2.02; 95% CI: 1.17-3.45), dyspareunia (OR: 2.07; 95% CI: 1.08-3.99), and sexual satisfaction disorders (OR: 2.75; 95% CI: 1.34-5.52) than women without FGM.

CONCLUSION: FGM is practiced in specific ethnic groups in the DRC, with ILE secondarily leading to long-term effects on pelvic floor and sexual function.

PMID:41813581 | DOI:10.1111/tmi.70114

JMIRx Med. 2026 Feb 27;6:e90221. doi: 10.2196/90221.

NO ABSTRACT

PMID:41813577 | DOI:10.2196/90221

JMIR Pediatr Parent. 2026 Mar 2;9:e80129. doi: 10.2196/80129.

ABSTRACT

BACKGROUND: Physical activity (PA) is essential for the healthy development of children. However, the pervasive presence of digital technologies has made digital gaming (DG) a prominent part of children’s everyday lives. As children grow up immersed in these digital environments, concerns about reduced PA have intensified. Given that adults, particularly parents and guardians, play a central role in guiding children’s behavior, their understanding of children’s motivational drivers for both PA and DG is of particular relevance.

OBJECTIVE: This study aimed to explore the motivational differences underlying children’s engagement in either PA or DG. Specifically, the study investigated five distinct motivational scales (recreation, social interaction, coping, competition, and skill) to determine which motives primarily drive behavior in each context. Also, it assessed whether adults accurately perceive these motives in children.

METHODS: Data were collected during events using an on-site questionnaire based on the Videogaming Motives Questionnaire. Both children and their accompanying adults completed parallel assessments regarding motives for PA and DG. The final sample included 94 participants forming 49 parent-child pairs. A 3-way mixed ANOVA with group as a between-subjects factor and activity and motive as within-subjects factors was conducted to examine group, activity, and motive effects and their interactions. To further explore these effects, a series of 2 × 5 repeated measures ANOVAs were conducted to examine the interaction between activity type and motivational dimension across groups, followed by separate multivariate tests per motive.

RESULTS: A significant interaction effect between activity type and motivational dimension emerged in the children’s data (F4,45=3.93, P=.008, partial η²=.259). Further analyses showed that motive competition was rated significantly higher for DG than for PA (F1,48=4.38, P=.04, partial η²=.084). Among adults, separate multivariate tests for each motivational dimension revealed the largest difference in perceived motive coping (F1,48=4.72, P=.01, partial η²=.123), with PA rated higher than DG. Additionally, a significant difference emerged for motive competition (F1,48=4.10, P=.05, partial η²=.079), indicating higher ratings for DG compared to PA.

CONCLUSIONS: The findings emphasize the complexity of children’s motivational profiles, suggesting that engagement in DG is not necessarily a sign of diminished interest in PA but rather reflects alternative, equally compelling motivations. This nuanced understanding challenges simplistic dichotomies and supports the need for balanced perspectives on children’s activity preferences. Importantly, no statistically significant differences were detected between children’s self-reported motives and adults’ perceptions of their children’s motives, suggesting a general tendency toward similar ratings rather than clear evidence of alignment. These insights can inform the development of more tailored strategies for promoting both physical and digital engagement in a healthy and complementary manner.

PMID:41813574 | DOI:10.2196/80129

JMIRx Med. 2026 Feb 27;7:e88830. doi: 10.2196/88830.

NO ABSTRACT

PMID:41813573 | DOI:10.2196/88830

Heart Lung Circ. 2026 Mar 10:S1443-9506(25)01698-1. doi: 10.1016/j.hlc.2025.09.016. Online ahead of print.

ABSTRACT

BACKGROUND: Effective management of volume overload is essential for improving the prognosis of heart failure (HF), which is often complicated by exacerbations and rehospitalisations. Psychosocial and behavioural factors significantly influence volume status. However, studies directly linking these factors to volume overload in patients with HF remain limited.

AIM: This study aimed to model the direct and indirect influences of social support, cognition, self-efficacy, consideration of future outcomes, and self-care on volume overload in patients with HF to guide volume management interventions.

METHOD: A cross-sectional study was conducted among 233 consecutively hospitalised patients with HF from a tertiary hospital in Chongqing, China (January-July 2023). Bioelectrical impedance analysis measured volume status, and psychosocial and behavioural variables were assessed using validated scales, including the Lubben Social Network Scale, Mini-Cog, General Self-Efficacy Scale, Consideration of Future Consequences Scale, and Self-Care of Heart Failure Index, Version 6.2 Behaviour Scale. Data were analysed using IBM SPSS Statistics, Version 26.0 and AMOS 24.0.

RESULTS: Among the patients (mean age=66.49±12.49 years; 43.35% women; 61.8% New York Heart Association stage III), 71% experienced volume overload. Path analysis showed that volume overload (oedema index) was directly and negatively associated with self-care maintenance (β=-0.263; p<0.001), cognition (β=-0.202; p<0.001), and self-efficacy (β=-0.199; p<0.01). Indirect negative effects were observed for social support (β=-0.203; p<0.001), self-care confidence (β=-0.090; p<0.001), and consideration of future outcomes (β=-0.057; p<0.001).

CONCLUSIONS: Factors such as social support, cognitive functioning, self-efficacy, future considerations, and self-care are significant contributors to the vulnerability of patients with HF to volume overload. This underscores the necessity for multifaceted interventions aimed at improving the prognosis of patients with HF.

PMID:41813559 | DOI:10.1016/j.hlc.2025.09.016