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Multimodal intervention benefits: Responder analysis of J-MINT PRIME Kanagawa trial.

INTRODUCTION: The J-MINT PRIME Kanagawa trial was an 18-month multimodal intervention (incorporating exercise, nutrition, and metabolic management) for dementia prevention. Because the primary analysis showed no significant benefits, we performed an exploratory responder analysis to identify responsive subpopulations. METHODS: We analyzed the Full Analysis Set comprising 188 participants. Classification and regression tree (CART) analysis, applied to the intervention arm, identified baseline predictors of cognitive improvement. These rules were then applied to the entire cohort to evaluate treatment effects on the Mini-Mental State Examination (MMSE) using fully adjusted mixed-effects models for repeated measures (MMRM). RESULTS: CART identified a "Target Group" (N = 108) characterized by baseline profiles such as an MMSE score < 28 or specific metabolic ranges (e.g., LDL-C < 135 mg/dL). Within this target group, the intervention significantly preserved MMSE trajectories compared with the control group (group &#xd7; time interaction, P = 0.022). In contrast, the Non-Target Group (N = 80), consisting of high-functioning individuals (MMSE &#x2265; 28), exhibited no significant group &#xd7; time interaction. DISCUSSION: Multimodal interventions may effectively preserve global cognition in older adults with sub-threshold cognitive decline. Careful targeting of appropriate populations, while considering potential longitudinal measurement artifacts (e.g., practice effects), is essential. These findings provide a hypothesis-generating framework that warrants external validation in future prevention trials.

Humans

Status of dementia care among healthcare practitioners in Nigerian tertiary hospitals: a cross-sectional study.

BACKGROUND/OBJECTIVES: Dementia is an escalating public health concern globally. This study evaluated the knowledge, attitudes, practices, and perceived barriers to dementia care among healthcare practitioners in Nigerian tertiary hospitals, aiming to identify practitioner-related sociodemographic predictors and systemic barriers affecting dementia care delivery. METHODS: We collected data from May 2024 to May 2025 for this cross-sectional study in 12 purposively selected tertiary hospitals across Nigeria's six geopolitical zones. Participants included physicians, nurses, pharmacists, and other professionals involved in geriatric psychiatric care. Using multistage and convenience sampling, 394 respondents were recruited (response rate: 99.5%). Data were collected via a validated Dementia Care Practice Questionnaire (Cronbach's &#x3b1; = 0.84) and analyzed with SPSS v22. Descriptive statistics, Chi-square tests, and odds ratios (ORs) identified associations (significance: p &#x2264; 0.05). RESULTS: Of 394 respondents, 51.5% were aged &#x2265;40 years, and 54.8% were female. While 62.9% demonstrated adequate knowledge, negative perceptions (51.3%) and attitudes (56.9%) were common. Despite this, 71.3% reported engagement in dementia care, and 75.6% demonstrated appropriate professional help-seeking behaviour when confronted with dementia care challenges. Practitioner-reported barriers included limited training opportunities, geographical barriers affecting patient access to dementia services, and inadequate staffing. Predictors of desirable care practices among healthcare practitioners included age &#x2265;40 years, female gender, Christian affiliation, and &#x2265;5 years of professional experience. CONCLUSION: Although many healthcare practitioners are involved in dementia care, gaps in perceptions, attitudes, and structural support persist. Interventions should focus on targeted training, system strengthening, and policy reform to improve dementia care outcomes.

Barriers to care

Interventions to Reduce Loneliness in Informal Caregivers of People With Dementia: A Systematic Review.

AIM: To summarize the current evidence on reducing loneliness among informal caregivers of people with dementia, such as family members or friends. DESIGN: A systematic review. METHODS: The methodological quality was evaluated using the revised Cochrane risk-of-bias tool for randomized controlled trials and the revised JBI critical appraisal checklist for quasi-experimental studies. Data were extracted as predefined and synthesized narratively. The Template for Intervention Description and Replication checklist was used to report the intervention characteristics. DATA SOURCES: Six electronic databases (MEDLINE via PubMed, EMBASE, Cochrane Library, PsycINFO, CINAHL Plus, and Web of Science Core Collection) were searched for studies published in peer-reviewed English journals from the inception of each database until 28 January 2024. RESULTS: Eight studies were included in this review, published between 2002 and 2023, with three being randomized controlled trials. All included interventions were psychosocial. Only one study reported significant improvements in loneliness. Five studies utilized remote and online interventions, such as social networking, psychotherapy, and online social support. Interventions varied in their impact on secondary outcomes, including stress, depressive symptoms, anxiety, and caregiver burden. Four studies demonstrated a positive effect on caregiver stress levels. One pilot trial reported a positive impact on depressive symptoms, and another study noted potential improvements in anxiety. One pilot study reported an average improvement in caregiver burden. CONCLUSION: While the evidence is insufficient for conclusive statements, this systematic review suggests potential benefits of interventions to reduce loneliness and improve mental health among these caregivers. It highlights the promise of remote interventions in addressing loneliness among dementia caregivers. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: The findings suggest that tailored interventions, especially those delivered remotely, can enhance the support provided to caregivers, potentially improving their mental health and overall well-being. REPORTING METHOD: This systematic review adhered to the PRISMA statement. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Humans

Effectiveness of psychosocial and lifestyle interventions in promoting behaviour change and improving cognitive outcomes in older people with memory concerns: A systematic review.

BACKGROUND: Older adults with mild cognitive impairment or subjective cognitive decline have a greater dementia risk, particularly those from minority ethnic and socioeconomically disadvantaged backgrounds. Psychosocial and lifestyle interventions targeting modifiable risk factors offer hope for reducing risk, yet behavioural mechanisms remain unclear. This systematic review examines these mechanisms and associated outcomes. METHOD: We searched PubMed, Embase (Ovid), PsycINFO (Ovid), Web of Science, and Scopus for randomised control trials testing interventions that aimed to improve lifestyle and cognition in older adults with memory concerns. We explored behavioural mechanisms using the COM-B model and synthesised intervention effectiveness, overall and within underserved groups. We prioritised lower risk of bias studies. RESULTS: 26 studies described 23 randomised controlled trials (14 multidomain, 9 single domain interventions). Certainty of evidence that behaviour change was associated with cognition was low. Moderate-certainty evidence indicated that interventions providing a socially supportive environment and combining nutritional education and counselling for 6&#x202f;+&#x202f;months improved diet. Physical activity improved primarily in interventions incorporating education, structured training, and enablement strategies (e.g., tailored programmes, providing tools). Interventions simultaneously targeting capability, opportunity and motivation showed greater overall effectiveness. Few studies recorded ethnicity (13%) or sociodemographic status (9%), and none explored their impact. CONCLUSIONS: Non-pharmacological interventions can help this population improve their lifestyles if they feel capable, equipped and motivated, highlighting the value of careful design and implementation. There is scarce evidence on how these interventions work for underserved populations. Future research should explore this to inform tailored interventions and develop equitable dementia prevention strategies.

Humans

Short-term aerobic exercise as an adjunct treatment for depression in acute geriatric psychiatry: Results of a randomized controlled trial.

BACKGROUND: This randomized controlled trial examined whether short-term aerobic exercise provided additional clinical benefit over an active control in older inpatients with depression in geriatric psychiatry. METHODS: 100 patients (mean age 76&#xa0;years) were randomized to 2-week supervised aerobic ergometer training (intervention group, IG) or a flexibility program (control group, CG), both delivered in addition to treatment as usual (TAU). Adherence, training exposure and adverse events were recorded to assess feasibility. The primary outcome was clinical improvement measured with the Clinical Global Impression of Change (CGI). Secondary outcomes included depressive symptom severity assessed by the Beck Depression Inventory-II (BDI-II) and clinician-rated Hamilton Rating Scale for Depression (HAMD), physical activity, 6-min walk test (6MWT) performance, and fluoxetine-equivalent antidepressant dose (FLX). RESULTS: Thirty-nine participants attended at least 80% of sessions, with lower adherence in the IG. Weekly training duration differed between groups (74.0&#xa0;&#xb1;&#xa0;31.9 vs. 95.0&#xa0;&#xb1;&#xa0;25.3&#xa0;min/week, p&#xa0;=&#xa0;.003). CGI did not differ between groups (IG: MD -0.31, 95% CI -0.67 to 0.05; p&#xa0;=&#xa0;.069). Depressive symptom severity decreased over time in both groups (p&#xa0;<&#xa0;.001), without significant between-group differences for HAMD (MD -0.22, 95% CI -2.55 to 2.12) or BDI-II (MD -0.62, 95% CI -3.68 to 2.45). 6MWT and FLX increased over time (both p&#xa0;<&#xa0;.001), without group differences (6MWT: MD -1.08&#xa0;m, 95% CI -20.04 to 17.89; FLX: MD 5.69&#xa0;mg/day, 95% CI -2.40 to 13.77). CONCLUSION: Short-term aerobic exercise was deliverable, but showed no additional clinical benefit over low-intensity flexibility during TAU. Further research should determine dose, duration and adherence for clinically relevant effects.

Humans

Subtle cortical thinning in the temporal pole in middle-aged APOE-&#x3b5;4 and PICALM (rs3851179) AA/AG carriers without dementia.

The symptoms of Alzheimer's disease (AD) are caused by neurodegeneration and atrophy in particular brain regions, especially in the temporal lobe. However, the influence of genetic risk on cortical thickness prior to dementia onset, remains unclear. This study aimed to explore the relationship between AD genetic risk (related to APOE and PICALM genes) and cortical thickness in selected regions of interest (ROIs) in middle-aged individuals without dementia. Sixty-nine (N&#x202f;=&#x202f;69) participants (34 females, 35 males; age: 55.45&#x202f;&#xb1;&#x202f;3.19) underwent magnetic resonance imaging (MRI). They were divided into three groups based on their genetic AD risk: A+&#x202f;P+&#x202f;(APOE/PICALM risk variants), A+P- (APOE risk variant, PICALM neutral variants), and the N group (APOE/PICALM neutral alleles). Cortical thickness was analyzed using CAT12 software (surface-based morphometry with the Destrieux atlas) based on T1-weighted MR images in five ROIs referred to as "the cortical signature of AD" in previous studies. The A+P- group had a thinner right temporal pole cortex than non-carriers after controlling for sex, age, and Raven's Progressive Matrices scores. Although this finding did not survive FDR correction across the 10 tested regions, it is consistent with our hypotheses and prior literature. No other differences in cortical thickness were found in the analyzed regions of AD "signature". The observed effect was restricted to single-risk APOE carriers without PICALM risk alleles. Therefore, further research is needed to understand the genetic interplay between these two genes in conferring AD risk.

Humans

Cardiovascular risks in psychiatric disorders and psychiatric risks in cardiovascular disorders: implications for prevention and clinical management - a large-scale umbrella review encompassing 76 meta-analyses.

OBJECTIVE: Psychiatric and cardiovascular disorders often co-occur, complicating their assessment and management. No umbrella review(UR) has summarized the meta-analytic evidence on the co-occurrence of psychiatric and cardiovascular disorders and assessed its credibility. METHODS: Meta-analytic systematic reviews of observational studies documenting the prevalence, risk factors, and outcomes associated with the co-occurrence of cardiovascular and psychiatric disorders, indexed from inception through March.16.2026, and meeting established diagnostic criteria, were included. Meta-analytic association and prevalence estimates were recalculated and graded based on established or adapted criteria. The AMSTAR-2 assessed the quality of the meta-analyses, while several subgroup analyses and meta-regressions aimed to explain the heterogeneity. RESULTS: We included 76 meta-analyses yielding 131 meta-analytic estimates. Based on pre-existing meta-analytic evidence, 22/24 prevalence estimates (91.7%) met moderate/strong credibility criteria. Strong credibility emerged for: orthostatic hypotension in Lewy body(58%;95%C.I.&#xa0;=&#xa0;50-66%) and Alzheimer's dementias(28.0%&#xa0;=&#xa0;95%C.I.&#xa0;=&#xa0;17.0-40.0%); pericardial effusion in anorexia nervosa(25.0%;95%C.I.&#xa0;=&#xa0;17.0-34.0%); in heart failure(HF): major depressive disorder(MDD)(41.9%;95%C.I.&#xa0;=&#xa0;36.7-47.1%), mild cognitive impairment(MCI)(41.4%;95%C.I.&#xa0;=&#xa0;38.3-45.6%), anxiety(32.0%;95%C.I.&#xa0;=&#xa0;26.5-37.6%), MDD&#xa0;+&#xa0;anxiety(24.7%;95%C.I.&#xa0;=&#xa0;17.9-34.3%), and dementia(19.8%;95%C.I.&#xa0;=&#xa0;12.9-27.8%); in atrial fibrillation(AF): MCI(26.0%;95%C.I.&#xa0;=&#xa0;21.0-30.0%), anxiety in patients undergoing pulmonary vein isolation(PVI)(25.0%;95%C.I.&#xa0;=&#xa0;12.0-46.0%), MDD in PVI patients (20.0%;95%C.I.&#xa0;=&#xa0;13.0-29.0%); in coronary artery disease: MDD&#xa0;+&#xa0;anxiety(19.8%;95%C.I.&#xa0;=&#xa0;16.0-24.6%): in schizophrenia spectrum disorders: clozapine-associated-cardiomyopathy(0.6%;95%C.I.&#xa0;=&#xa0;0.2-2.3%); clozapine-associated-cardiomyopathy absolute death rates (0.0003;95%C.I.&#xa0;=&#xa0;0.0001-0.0012); clozapine-associated-cardiomyopathy case fatality rate (0.078;95%C.I.&#xa0;=&#xa0;0.018-0.285). Several additional disorders were multimorbid in>5% of people, yet with a lower credibility rating. No re-pooled risk factors/outcomes reached strong credibility criteria. CONCLUSIONS: The present study provides an atlas of cardiovascular and psychiatric multimorbidity across varying levels of credibility, reinforcing the need for an integrated, multidisciplinary approach to patient care and for more research on actionable risk/protective factors and outcomes.

Humans

The feasibility and efficacy of weighted blankets as a sleep intervention for people with behavioural and psychological symptoms of dementia: a pilot randomised crossover trial.

Sleep disturbances contribute to disease progression in dementia and result in reduced quality of life. Non-pharmacological interventions are recommended for the management of sleep and other behavioural and psychological symptoms of dementia (BPSD), although these interventions can be challenging to implement. This pilot study assessed the feasibility and efficacy of weighted blankets as a sleep intervention for people with BPSD in a neurobehavioural unit. Fourteen residents, serving as their own control, slept two weeks with a weighted blanket and two weeks with usual bedding in a crossover trial. The primary outcomes were sleep duration and efficiency, measured via a Withing's sleep analyser and sleep disordered behaviours, measured by the sleep disorder inventory (SDI). Secondary outcomes included responsive behaviours, measured by the Neuropsychiatric index (NPI), falls incidents, restrictive practice incidents and use of pro re nata psychotropic medications. Generalised Estimation Equation (GEE) method was used for analysis. There was no statistical evidence that weighted blankets improved sleep or behavioural outcomes for people with BPSD, however fewer fall incidents, wakings and restrictive practices were reported during weighted blanket use. Weighted blankets were considered feasible and acceptable with high recruitment rates, nil participant withdrawals and no adverse outcomes, however there was variable compliance to the intervention protocol and the Withings did not adequately measure sleep. Whilst there is insufficient effectiveness evidence for further trials, weighted blankets can be offered to people living with dementia as a low risk sleep intervention option, with the caveat that there is currently no effectiveness evidence.

Behavioural Symptoms

Apoptosis protein markers in comorbid type 2 diabetes mellitus and depression; relationships with cognitive performance, incident dementia, and white matter hyperintensities.

Type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) are reciprocal risk factors, and both elevate dementia risk. Dysregulation of programmed cell death is implicated in T2DM, MDD, and neurodegeneration, but proteomic markers of apoptosis have yet to be studied as dementia predictors in people with T2DM and/or MDD. This study examines apoptosis markers in comorbid T2DM and MDD, and their associations with cognitive, dementia, and neuroimaging outcomes. The retrospective sample (n&#xa0;=&#xa0;15,765) consisted of UK Biobank participants (MDD only n&#xa0;=&#xa0;1230; T2DM only n&#xa0;=&#xa0;3644; comorbid T2DM&#xa0;+&#xa0;MDD n&#xa0;=&#xa0;721). Individuals with T2DM&#xa0;+&#xa0;MDD comorbidity had poorer cognitive performance, and a higher 15-year dementia incidence (HR&#xa0;=&#xa0;4.44, 95% CI&#xa0;=&#xa0;[3.23,6.11]). Among 60 apoptosis-related proteins identified by Kyoto Encyclopedia of Genes and Genomes pathway enrichment, 41 were significantly up-regulated in comorbid T2DM&#xa0;+&#xa0;MDD relative to controls, and 4 were higher in the comorbid group than both T2DM alone and MDD alone. Tumor necrosis factor ligand superfamily member 10 (TNFSF10), growth arrest and DNA damage-inducible protein GADD45 beta, tumor necrosis factor ligand superfamily member 6, and RAC-gamma serine/threonine-protein kinase were associated with dementia risk. Nine proteins (e.g. apoptosis-inducing factor 1, mitochondrial, caspase-2, mitogen-activated protein kinase kinase kinase 5, TNFSF10), were associated with white matter hyperintensity volumes in comorbid T2DM&#xa0;+&#xa0;MDD after FDR correction, but none were associated with cognitive performance, atrophy, or white matter microstructural changes. These findings identify peripheral apoptosis markers that were further elevated in comorbid T2DM&#xa0;+&#xa0;MDD compared to either alone, pointing to an important pathophysiological element underlying adverse outcomes in the context of mood and metabolic comorbidity.

Humans

Artificial intelligence enabled social robotic interventions (PARO) in Australian dementia care: A systematic review and meta-analysis.

BACKGROUND: Although there is a growing body of research indicating that Personal Robot/Social Robot could be used in various aspects of care for individuals with dementia, little is known about how well these types of interventions work in an actual hospital setting in Australia. AIMS & OBJECTIVES: The objective of the present systematic review and meta-analysis is to assess the effectiveness of PARO-based socially assistive robotic intervention in terms of its effectiveness outcomes towards the reduction of dementia-related behavioural and psychological symptoms in Australian based healthcare settings. METHODS: A systematic search was conducted across five electronic databases, including MEDLINE (PubMed), EMBASE, CINAHL, PsycINFO, and the Cochrane Library, to identify randomised controlled trials (RCTs) investigating PARO-based socially assistive robotic interventions for dementia in Australian healthcare settings. This review was registered with PROSPERO (CRD420251251916) and followed the PRISMA 2020 guidelines. In addition, the Cochrane Risk of Bias tool (RoB 2) was used to evaluate the risk of bias across all studies. Pooled standardised mean differences (SMD) with 95&#xa0;% confidence intervals (CI) were calculated for agitation, anxiety, and depression. Heterogeneity across studies was evaluated using the I2 statistic. RESULTS: Six RCTs involving 1444 participants were identified for inclusion in this review. AI-enabled socially assistive robotic interventions, specifically the PARO therapeutic robot, significantly reduced agitation and anxiety when compared to standard treatment or control conditions. The pooled analysis showed that agitation [SMD&#xa0;=&#xa0;-0.44 (95&#xa0;% CI: -0.70, -0.18) p&#xa0;=&#xa0;0.0008] and anxiety [SMD&#xa0;=&#xa0;-0.59 (95&#xa0;% CI: -0.91, -0.27) p&#xa0;=&#xa0;0.0003] were reduced significantly, while the decrease in depression [SMD&#xa0;=&#xa0;-0.44 (95&#xa0;% CI: -0.95, -0.07) p&#xa0;=&#xa0;0.09] scores was non-significant among dementia patients receiving PARO-based socially assistive robotic interventions as compared to the control. The overall risk of bias across all six studies was considered low to moderate. CONCLUSION: PARO-based socially assistive robotic interventions may provide preliminary evidence of effectiveness in reducing agitation and anxiety in individuals with dementia in Australian healthcare, but the evidence regarding the reduction of depression remains unclear. Therefore, additional high-quality trials with consistent methodology and extended follow-up will be necessary to determine both the short-term and long-term clinical efficacy and practicality of implementing these interventions into practice.

Humans

Intervention Without Borders - an Automated Self-Guided AI-Enhanced Psychoeducation Intervention for Dementia Caregivers: Parallel-Group Randomized Waitlist-Controlled Trial.

OBJECTIVE: To examine whether a fully automated, self-guided intervention (PDC30) could improve caregiver well-being over a 1-month waitlist control in an international sample. DESIGN: Randomized waitlist-controlled trial. SETTING: Web-based platform accessible globally. PARTICIPANTS: 441 individuals responded to study promotion on the internet, of whom 274 from 43 countries met the study criteria and were randomized. Eligible participants were adults providing &#x2265;10 care hours weekly to community-dwelling relatives with dementia, scoring &#x2265;5 on Patient Health Questionnaire-9 (PHQ-9), and without recent caregiver intervention. INTERVENTION: Available 24/7, PDC30 is a self-guided, automated intervention consisting of a Guidebook, an AI-powered counseling chatbot, and interactive applications for cognitive-behavioral techniques, relaxation, and caregiver-recipient bonding. MEASUREMENTS: At baseline and follow-ups at 1, 2, and 3 months, depression was assessed by PHQ-9. Secondary outcomes were measured with validated brief versions of anxiety, burden, and positive gains. RESULTS: Intent-to-treat analysis using mixed-effects regression showed treatment x time2 effects on all outcomes except anxiety. At 1-month follow-up, coinciding with exclusive access to PDC30, intervention caregivers showed significant improvements in depression (d = -0.37), burden (d = -0.34), and positive gains (d = 0.42). The differences mostly disappeared after control participants received the intervention, while improvements in both groups were sustained thereafter. Participants reported using the website several times weekly, were generally satisfied with it, and found the chatbot most helpful. CONCLUSIONS: The effects on depression and other outcomes were consistent with those observed for in-person programs, suggesting the viability of well-designed automated intervention. The study demonstrates the feasibility, acceptability, and potential global health impact of PDC30.

Humans

Complement component C4 and neuroimaging in psychiatry: A systematic review.

INTRODUCTION: Genomic, transcriptomic, and proteomic studies suggest that the complement system contributes to the pathophysiology of various psychiatric disorders partly through neurodevelopmental effects linked to C4A protein levels variations. We conducted a systematic review to characterize how brain micro- and macrostructure and connectivity vary with proxies of in vivo brain C4A protein levels in both psychiatric and general-population cohorts. METHODS: We used Medline, Web of Science, and Embase, and included all studies published before April 14, 2025. Inclusion criteria were: (1) inclusion of healthy controls and/or individuals with psychiatric disorders assessed according to recognized diagnostic manuals (DSM or ICD); (2) use of MRI-based neuroimaging; and (3) use of genomic, transcriptomic and/or proteomic approaches as proxies of in vivo brain C4A proteins levels. RESULTS: From 317 identified articles, 11 were included. Associations between C4A levels and brain structure were heterogeneous across regions. Only the mOFC, dlPFC, and entorhinal cortex were implicated in more than one study. Findings for the mOFC and dlPFC varied by the type of metrics and clinical status, whereas higher C4A levels were more consistently associated with smaller entorhinal cortex surface area and cortical thickness in pediatric, middle-aged, and older general-population cohorts. In addition, one study found higher genetically predicted C4A expression to be associated with higher TSPO levels. CONCLUSION: The limited number of available studies and their methodological heterogeneity make synthesis challenging. However, biological hypotheses such as excessive synaptic pruning or broader inflammatory effects on the brain may provide plausible explanatory frameworks for the reported associations.

Humans

Perinatal depression, maternal thyroid status and fetus/infant health and development: A systematic review.

BACKGROUND: Thyroid hormones are known to influence both maternal depression and child developmental outcomes, while maternal depression independently affects child outcomes. The potential interaction between thyroid dysfunction and depression in shaping child development remains insufficiently explored. The present study addresses such interplay. METHODS: Following PRISMA 2020 and JBI guidelines, three databases were searched through December 2025 for primary studies on maternal thyroid status, perinatal depression, and child development. Risk of bias (RoB) was assessed using validated tools. Due to clinical and methodological heterogeneity, data were synthesized narratively following SWiM guidelines. RESULTS: Eleven studies were included. Beyond independent risks for preterm birth and behavioral problems, limited evidence supports a synergistic model, while most studies likely reflect the simple co-occurrence of risks. Maternal thyroid peroxidase antibodies (TPO-Ab) were associated with child externalizing problems exclusively in the presence of clinical depression. High depressive symptoms also attenuated the cognitive benefits of prenatal iodine supplementation. Thyroid status appears to function as a risk moderator rather than a mediator. However, 50% of observational studies presented high RoB, primarily due to participant attrition. CONCLUSION: Findings are still scarce to support a synergistic risk model where specific maternal thyroid parameters (i.e. thyroid autoimmunity and iodine status) may moderate the impact of depressive symptoms on child development. Despite the high RoB in half of the studies, results highlight the need for integrated screening protocols. Simultaneously assessing mental health and thyroid status may optimize risk stratification for high-risk mother-infant dyads.

Female

Impact of Chewing Behavior Change on Cognition and Cerebral Hemodynamics.

BACKGROUND: Impaired chewing ability is a recognized risk factor for cognitive decline in older adults, potentially due to reduced neural stimulation in cognition-related brain regions. While short-term studies have demonstrated transient increases in neural activity from chewing, the sustained cognitive and neurophysiological effects of encouraging thorough chewing habits in daily life remain unclear. OBJECTIVE: This randomized controlled trial investigated whether promoting thorough chewing during meals could improve cognitive function and cerebral hemodynamics in older adults. METHODS: Fifty participants aged 65 y or older were randomly assigned to either a 1-mo intervention group, which used a wearable device to monitor and increase chewing strokes during meals, or a control group that maintained usual chewing habits. Chewing behavior, cognitive performance (including memory and executive function via the color Stroop test), and cerebral hemodynamics in the dorsolateral prefrontal cortex (DLPFC) were measured at baseline and after 1 mo. Statistical analyses included t tests, chi-square tests, 2-way analysis of variance with post hoc tests, Pearson correlations, and generalized linear models to evaluate group differences and associations between chewing and cognitive outcomes. RESULTS: Significant time-by-group interactions were observed for memory, F(1, 48) = 6.24, P = 0.043, and hemodynamic responses in the left DLPFC, F(1, 48) = 6.19, P = 0.013. The intervention group showed increased chewing frequency (P = 0.017), improved memory performance, and reduced left DLPFC responses compared with controls. Chewing frequency was positively correlated with Stroop test scores (r = 0.53, P = 0.010) and negatively with hemodynamic changes in the left DLPFC (r = -0.30, P = 0.040). Although improvements in other cognitive outcomes and hemodynamic measures favored the intervention group, these differences did not reach statistical significance. CONCLUSIONS: Promoting intentional chewing habits for 1 mo may enhance memory-related cognitive performance and neural efficiency in the DLPFC during working memory tasks in older adults. This nonpharmacologic, low-burden strategy warrants further research with longer interventions to support cognitive health and dementia prevention. TRIAL REGISTRATION ID: UMIN000044280Knowledge Transfer Statement:This study demonstrates that promoting thorough chewing habits in older adults can improve memory and enhance neural efficiency in the brain. Encouraging intentional mastication is a simple, nonpharmacologic approach that may help maintain cognitive health and prevent dementia, providing a practical strategy for clinicians and policymakers to support healthy aging.

Humans

Brief Report: Beyond Testing: Exploring the Psychosocial Impact of HIV Self-Testing Among Ugandan Gender-Diverse Sex Workers.

BACKGROUND: The psychosocial effect of HIV self-testing (HIVST) on sex workers' self-esteem, depression, alcohol misuse, perceived sex work stigma, and empowerment remains poorly characterized. We hypothesized that HIVST would reduce sex work stigma and improve these psychosocial outcomes by enabling private, autonomous testing and reducing exposure to stigmatizing healthcare encounters. SETTING: Kampala, Uganda. METHODS: We conducted a secondary analysis of the Empower study (NCT03426670), an open-label randomized trial in which 117 cisgender female, transgender female, and cisgender male sex workers were assigned 1:1 to monthly HIVST plus quarterly clinic-based testing, or to quarterly clinic-based testing alone, and followed for 12 months. Self-esteem (Rosenberg Self-Esteem Scale), depressive symptoms (PHQ-2), alcohol misuse (RAPS4), perceived sex work stigma (adapted Female Sex Worker Stigma Scale), and empowerment were assessed quarterly. Mixed-effects regression models, adjusted for baseline values, evaluated intervention effects. RESULTS: Data from 117 participants were analyzed, including 7 early disenrollments. Over 12 months, HIVST participants reported significantly lower perceived sex work stigma than standard of care participants (&#x3b2; = -0.38, P = 0.04; monthly reduction P = 0.003), although the rate of decline did not differ significantly between arms (interaction P = 0.08). Self-esteem and depressive symptoms improved in both arms, with no between-arm differences (interaction P = 0.41 and 0.32). Alcohol misuse and empowerment showed no significant arm differences. CONCLUSION: HIVST may reduce sex work stigma without adverse psychosocial effects, supporting its integration into combination HIV prevention for gender-diverse sex workers in sub-Saharan Africa.

Humans

Chronic neurological diseases with acute respiratory failure in a real-life cohort: insights into ICU and long-term survival-A retrospective study.

BACKGROUND: Patients with chronic neurological diseases (CND) are at increased risk of pulmonary complications that often require ICU admission. This study aimed to identify clinical factors associated with ICU mortality and long-term survival in patients with CND who developed acute respiratory failure (ARF). METHODS: This retrospective cohort study was conducted in a level III respiratory ICU. Patients with pre-existing CND admitted to the ICU with ARF were included. ICU mortality was analyzed using multivariable logistic regression. Long-term survival after ICU discharge was evaluated using Kaplan-Meier survival analysis and Cox proportional hazards models. Mortality timing was further characterized using hazard function analysis. RESULTS: A total of 220 patients were included; the most common neurological diagnoses were dementia (37.3%), stroke (22.7%), and amyotrophic lateral sclerosis (14.1%). ICU mortality was 33.6%. Higher APACHE II scores were independently associated with increased ICU mortality (OR 1.076 per point increase; 95% CI 1.029-1.126; p&#xa0;<&#xa0;0.001). Long-term survival differed significantly by post-discharge respiratory support strategy, with Kaplan-Meier analysis demonstrating more favorable survival patterns among patients receiving home non-invasive mechanical ventilation (NIMV) (p&#xa0;=&#xa0;0.003). In Cox regression analysis, age, home NIMV, and feeding modality at discharge were independently associated with long-term outcomes. Survival analyses revealed an early clustering of deaths within the first months after ICU discharge, particularly among patients with dementia. CONCLUSIONS: In patients with CND, acute physiological severity was the main determinant of ICU mortality, whereas long-term survival after ICU discharge was poor, with deaths clustering within the first months thereafter. Post-discharge respiratory support and nutritional management should be individualized according to the expected clinical trajectory and patient values.

Humans

Mixed Methods Findings from a Stepped Wedge Hybrid Implementation Trial of ATTAIN NAV: A Mental Health Family Navigation Intervention for Autistic Youth.

ATTAIN NAV (Access to Tailored Autism Integrated Care through Family Navigation) was delivered by family navigators to promote access to and engagement with mental health services for school-age autistic youth. This study used a mixed method, stepped wedge design to test the effects of family navigation on service and clinical outcomes while gathering information on implementation. Primary care providers from six clinics in California and 56 caregiver-child dyads enrolled in and completed the study. Clinics were randomized to either a technology-enhanced or standard family navigation condition. Caregivers completed assessments at baseline and post about child, family and services outcomes, and a subset participated in a post qualitative interview. Quantitative findings demonstrated improvements in child challenging behavior and parent activation across conditions although these improvements were more pronounced for families in the standard FN condition. At post-intervention, families in the standard FN condition reported higher levels of navigation satisfaction, a shorter time to attend their first mental health appointment, and higher engagement with their navigator. Qualitative findings complemented and expanded the quantitative survey findings. The ATTAIN NAV model of family navigation for autistic children with co-occurring mental health needs demonstrates promising implementation, service, and clinical benefits. Clinical Trials Registration. NCT05344378.

Humans

Elastic tape as an add-on strategy to potentiate pulmonary rehabilitation outcomes in nonobese males with moderate-to-very severe COPD: A randomised clinical trial.

BACKGROUND AND OBJECTIVE: Pulmonary rehabilitation (PR) improves exercise capacity but has limited effects on ventilatory constraints in severe COPD. Application of elastic tape (ET) is a potential adjunctive strategy that improves ventilatory efficiency, but its effects during PR remain un lear. This study investigated whether ET potentiates PR benefits on exercise capacity, health status, psychological symptoms, and health-related quality of life (HRQoL) in individuals with COPD. METHODS: Forty-two nonobese men with moderate-to-very severe COPD were randomised to ET or Sham groups during an 8-week PR programme. The primary outcome was endurance shuttle walk test (ESWT) time; secondary outcomes included COPD Assessment Test (CAT), Chronic Respiratory Questionnaire (CRQ), and Hospital Anxiety and Depression Scale (HADS). RESULTS: ESWT improved by +329s in the ET group, exceeding the MCID. Greater CAT improvements (p&#x2009;=&#x2009;0.02), and a higher proportion achieving minimal clinically important difference (MCID) (48% vs. 29%; p&#x2009;=&#x2009;0.02) were observed in the ET group. Only ET group achieved MCIDs for depression (p&#x2009;=&#x2009;0.003) and anxiety (p&#x2009;=&#x2009;0.02). HRQoL improved similarly in both groups. The only outcome with a significant time&#x2009;&#xd7;&#x2009;group interaction was HADS-D (p&#x2009;=&#x2009;0.001), improved by ET. Only This study was performed in accordance with the Declaration of Helsinki. This human study was approved by Ethics Committee for Analysis of Research Projects (CAPPesq) of School of Medicine of the University of S&#xe3;o Paulo - Hospital das Cl&#xed;nicas (approval 55 617 321.20000.0068). All adult participants provided written informed consent to participate in this study. Clinical Trial Registration number NCT05939999 (https://clinicaltrials.gov), registered on October 26th, 2025.ET group presented moderate-to-large effect sizes for ESWT (d&#x2009;=&#x2009;0.89), HADS-A (d&#x2009;=&#x2009;0.51) and HADS-D (d&#x2009;=&#x2009;1.02). CONCLUSIONS: ET potentiates PR benefits on exercise capacity, health status, and psychological symptoms in individuals with moderate-to-very severe COPD.

Humans