Epilepsy is a common neurological disorder in the United States that disproportionately affects African Americans. Religious and spiritual practices are important coping mechanisms that may influence health beliefs and healthcare decisions, yet their influence on epilepsy outcomes in this population remains understudied. This narrative review examines how religious and spiritual practices contribute to health decision making behaviors among African Americans living with epilepsy. A literature search was conducted using PubMed, Google Scholar, Connected Papers, and the New York University Library system, focusing on religiosity and spirituality in chronic illness, epilepsy outcomes, racial disparities, stigma in faith-based settings, and church-based health interventions. Across the reviewed literature, findings showed that religiosity and spirituality were associated with coping, finding purpose, social support, and quality of life. In epilepsy-specific studies, positive religious and spiritual coping associated with better well-being, lower anxiety and depressive symptoms, and higher quality of life, while negative religious coping was associated with poorer psychosocial outcomes. Direct evidence among African Americans with epilepsy was limited; however, available findings suggest that Black patients relied more on religion, emotional support, positive reframing, and denial as coping strategies compared to White patients. Overall, this review highlights the need to better understand how African Americans with epilepsy use religious and spiritual frameworks to manage living with a chronic neurological condition.

Gabapentin and duloxetine are common treatments for neuropathic pain in adults over 65, but data on their gastrointestinal (GI) bleeding risk are limited. We compared GI bleeding risk after starting gabapentin or duloxetine in this population. We used the TriNetX US Collaborative Network to conduct an active-comparator cohort study using target trial emulation. Patients aged 65 years and above with neuropathic pain diagnosed between January 2020 and December 2024 were included, excluding those with prior GI bleeding, major depressive disorder, or thrombocytopenia. Propensity score matching balanced key covariates. The main outcome was GI bleeding within 24 months, analyzed with Cox regression; secondary analyses included upper/lower GI bleeding, mortality, and hospitalization. Negative controls assessed confounding. The study analyzed 62,926 patients (55,236 gabapentin; 7,690 duloxetine) and matched 7,599 pairs. GI bleeding was less common with gabapentin initiators (1.22%) than duloxetine initiators (2.49%), showing an absolute risk reduction of 1.27% (HR 0.86, 95% CI 0.84-0.89, p < 0.0001), mainly for upper GI bleeding (HR 0.39, 95% CI 0.29-0.53). Lower GI bleeding results were not significant. Gabapentin also showed slightly lower all-cause mortality (HR 0.87, 95% CI 0.84-0.90). Negative control outcomes revealed no notable associations. In older adults with neuropathic pain, gabapentin initiation was associated with a lower risk of GI bleeding than duloxetine, especially for upper GI bleeding. As both drugs offer comparable analgesic efficacy, GI bleeding risk may be a relevant consideration when choosing between them. These findings are hypothesis-generating and should be confirmed in independent datasets and prospective comparative studies will confirm the data.

BACKGROUND: Higher sport specialization levels have been associated with increased mental health issues. A recently validated questionnaire, the Wisconsin Sport Specialization Questionnaire (WISSQ), may provide clarity about the degree of sport specialization to investigate associations with mental health/quality of life (QoL) among adolescent athletes. PURPOSE: To examine the association of sports specialization, as measured by the WISSQ, and mental health/QoL outcomes among uninjured adolescent athletes, as well as the effect of age on the interaction between mental health/QoL outcomes and sport specialization. STUDY DESIGN: Cross-sectional study; Level of evidence, 2. METHODS: During the preseason assessment, performed in July and August from 2023 to 2025, participants completed the WISSQ and the Patient-Reported Outcomes Measurement Information System (PROMIS) Global 25 (Version 1.1). A multiple linear regression model was constructed that evaluated the association between 6 PROMIS domains and WISSQ ratings, adjusting for age, sex, and self-reported physical activity volume. To address the secondary purpose, linear regression models with an interaction term were used to examine the association between each PROMIS domain and age with sport specialization. RESULTS: A total of 251 uninjured adolescent athletes completed the study (mean ± SD age, 15.9 ± 1.4 years). The mean WISSQ rating was 54.1 (SD, 15.4). Results from the multivariable linear regression model indicated that higher depressive symptoms (β = 0.46; 95% CI, 0.16-0.76; = .003) and pain interference ratings (β = 0.30; 95% CI, 0.02-0.57; = .03) were significantly associated with higher WISSQ ratings, after adjusting for baseline physical activity, age, sex, and history of anxiety or depression diagnosis. For the secondary purpose, there was a significant interaction between fatigue and age group on sport specialization (β coefficient = 0.49; 95% CI, 0.02-0.95; = .04). The relationship between fatigue and sport specialization differed by age: a stronger association occurred among older adolescents than younger adolescents. There were no other age × QoL interactions. CONCLUSION: This study demonstrated that higher depressive symptoms and pain interference ratings were significantly associated with higher WISSQ ratings. In addition, there was a significant interaction between fatigue and age group, with a stronger association identified among older adolescents. Higher specialized and older adolescent athletes may be more at risk for developing mental health/QoL concerns and may benefit from more targeted screening.

BACKGROUND: People with multiple sclerosis (pwMS) often experience impaired quality of life (QoL) despite receiving standard care. Digital therapeutics (DTx) may offer support, but prior trials yielded mixed results, possibly due to active controls and high baseline QoL. OBJECTIVES: We evaluated a DTx (levidex) as an adjunct to treatment as usual (TAU) in pwMS with impaired QoL. METHODS: In this pragmatic, online randomized controlled trial (LAMONT; NCT06090305),  = 470 pwMS with a score ≥ 2 on the Hamburg Quality of Life Questionnaire in Multiple Sclerosis (HAQUAMS) were randomized to levidex + TAU or TAU alone. The primary endpoint was HAQUAMS total score at 6 months, analysed by intention-to-treat analysis of covariance. RESULTS: Compared with TAU, levidex + TAU improved multiple sclerosis-specific QoL at 6 months (baseline-adjusted mean difference -0.10; 95% CI -0.18 to -0.03;  = 0.008; Cohen's  = 0.26). Clinically relevant HAQUAMS improvement (≥0.22) occurred more often with levidex (39.5% vs. 27.8%; number needed to treat = 9). Benefits also emerged for depressive symptoms and social/work functioning but not for anxiety. No serious adverse events occurred, and user satisfaction was high. CONCLUSIONS: In pwMS with impaired QoL, adding the scalable DTx levidex to TAU yields meaningful improvements in QoL and functioning.

This perspective article introduces Gender Affirming Psychiatry (GAP), a conceptual framework that integrates queer phenomenology, the gender minority stress model, and gender-affirming care to guide psychiatric assessment, formulation, and treatment of transgender and gender diverse (TGD) youth. This approach acknowledges the cultural and institutional structures that negatively impact the mental health of gender diverse youth, while leveraging resilience, community connection, and support structures that are known to improve mental health outcomes. In this time of greater awareness and increased scrutiny, GAP is a practical, person-centered approach that is clinically sound and ethically grounded.

Infectious bursal disease virus (IBDV) causes severe immunosuppression diseases in poultry, resulting in substantial economic losses for the global poultry industry. This study aimed to characterize circulating IBDV strains in Egyptian chicken flocks and assess their potential impact on poultry health and production. We conducted a passive surveillance study by collecting bursal samples from a total of 30 flocks, including commercial broilers, layers, and Baladi chickens, across nine Egyptian governorates in 2025. These flocks exhibited clinical signs of depression, along with kidney and bursal lesions indicative of IBDV infection. Pooled bursal homogenates were tested using RT-PCR with VP2-specific primers, revealing that 20 flocks (66.6%) tested positive for IBDV. Field and vaccine strains were distinguished by phylogenetic clustering of the VP2 hypervariable region (HVR) sequences against reference vaccine strains (D78, Winterfield 228, VAXXITEK), strains that cluster closely with reference vaccine strains are classified as vaccine-origin, whereas field strains are distinct branches indicate circulating wild-type or vvIBDV. Ten representative positive samples were inoculated in specific pathogen-free embryonated chicken eggs (SPF-ECE). The inoculated embryos exhibited haemorrhage, skull swelling, and liver necrosis with a pale-yellow appearance, along with congestion and thickening of the chorioallantoic membrane (CAM). Phylogenetic analysis of the partial VP2 gene classified the isolates according to the unified genogroup nomenclature: the majority of isolates belonged to the A3 (vvIBDV) genogroup, while one isolate clustered within the A2d (nVarIBDV) genogroup. These findings highlight the co-circulation of both virulent and variant IBDV strains in Egyptian chicken flocks, complicating disease control and demanding a continued surveillance and periodic re-evaluation of vaccination programs.

Cognitive-behavioral therapy (CBT) is the first-line treatment for obsessive-compulsive disorder (OCD), yet a significant number of patients do not achieve remission or substantial symptom relief. This study aims to enhance the prediction of CBT outcomes in OCD by integrating demographic, clinical, and neuroimaging data using machine learning (ML) models. We conduct a comprehensive analysis on a well-characterized clinical sample, employing a rigorous validation scheme to avoid data leakage, and comparing multiple ML algorithms to minimize bias. Out of four different ML models trained on demographic and clinical data, structural MRI, and resting-state MRI functional connectivity data, no model was able to predict CBT success significantly above chance level in the present sample. Although clinical and demographic data enabled 64%-66% accuracy for predicting remission, this did not reach statistical significance after permutation testing. Pre-treatment symptom severity emerged numerically as the most promising predictor of remission, aligning with previous studies, but did not pass the significance threshold in the present study. Despite efforts to identify neuroimaging predictors, neither functional nor structural MRI features significantly contributed to the prediction models. These findings suggest that robust, individualized brain-based predictions for mental health outcomes remain challenging with the available data and sample size.

BACKGROUND: Vascular depression (VaD) is a subtype of late-life depression (LLD) associated with cerebrovascular disease, cognitive impairment, and poor response to standard antidepressants. Despite its clinical relevance and association with increased risk of dementia, no specific treatment guidelines currently exist. OBJECTIVES: To systematically review randomised controlled trials (RCTs) on the clinical efficacy of pharmacological and non-pharmacological interventions for VaD in older adults. METHODS: A systematic search of MEDLINE, EMBASE, Web of Science and ClinicalTrials.gov registry identified 7994 records, of which 8 RCTs met inclusion criteria. Studies included participants with late-life VaD. Interventions comprised pharmacological treatments (augmentation with tandospirone and nimodipine) and neuromodulation techniques (rTMS and tDCS). Outcomes included treatment response and remission, change in depressive symptoms, and other clinical outcomes. RESULTS: Augmentation with tandospirone was associated with faster early symptom improvement in three of four trials. Nimodipine improved remission at 2 months and reduced recurrence in one of two trials. Neuromodulation interventions showed promising antidepressant effects and cognitive benefits (based on two trials). Treatments were generally well tolerated. However, study heterogeneity, small sample sizes, and short follow-up durations limited comparability and precluded meta-analysis. The overall certainty of evidence was low to very low. CONCLUSIONS: Evidence on treatment for VaD remains limited, highlighting the need for large, well-designed RCTs and integrated approaches combining vascular risk management with targeted therapies.

BACKGROUND: Sepsis-associated encephalopathy (SAE) often leads to cognitive impairment and even life-threatening conditions. Its pathophysiology is complex but remains unclear. We investigated the role of the mediodorsal thalamic nucleus-medial prefrontal cortex (MD-mPFC) pathway in alleviating cognitive dysfunction in a mouse model of cecal ligation puncture (CLP)-induced sepsis. METHODS: Neural projections from the MD to the mPFC were identified through retrograde tracing and viral expression. The MD-mPFC pathway was chemogenetically activated. Immunofluorescence staining was performed to determine the count of c-Fos-positive neurons in the mPFC cells. Cognitive functions of the mice were assessed using the Morris water maze, Barnes maze, novel object recognition, and open field tests. The expression of glutamate receptors and the downstream signaling molecules in the mPFC was determined through western blotting. RESULTS: MD-mPFC pathway activation alleviated cognitive dysfunction and anxiety-like behavior in the CLP-induced sepsis mouse model. The inhibition of glutamate receptors led to a decrease in the expression of c-Fos, a marker of neuronal activity, in the mPFC of the mice, indicating that glutamate receptors mediated the positive effects of the MD-mPFC pathway. Activation of the MD-mPFC pathway also led to increased levels of NMDAR, AMPAR, and downstream signaling molecules including CaMKIIa, p-CREB, and brain-derived neurotrophic factor in the mPFC. However, this increase was restrained by the inhibition of glutamate receptors using 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline(NBQX), an AMPAR inhibitor, or the NMDA receptor antagonist D-2-amino-5-phosphonopentanoate(D-AP5). CONCLUSION: The MD-mPFC pathway alleviated cognitive dysfunction in the mouse model of CLP-induced sepsis. Our findings highlight the role of glutamate receptors and the downstream signaling pathways as potential therapeutic targets for SAE-induced cognitive dysfunction and shed light on pathogenetic mechanism for SAE.

BACKGROUND: Pulmonary rehabilitation (PR) has been widely studied and established as an effective intervention in several chronic pulmonary diseases. Nevertheless, evidence in adults with asthma remains inconclusive. OBJECTIVE: . To assess the efficacy of PR, including at least education and exercise training (ET), in adults with asthma. METHODS: . This systematic review followed PRISMA guidelines. Four databases were searched from inception to November 2025. We included randomized clinical trials in adults with asthma who underwent a PR intervention compared to other interventions (including PR within education and ET components), usual care, or no intervention. Primary outcomes were asthma control, lung function, exercise capacity, and airway inflammation. Certainty of evidence and risk of bias were assessed. RESULTS: . Sixteen studies were included, and thirteen in at least one meta-analysis. Most studies enrolled moderate-to-severe asthma. Meta-analysis results showed significant differences in favor of PR in asthma control, exercise capacity, quality of life, anxiety, and depression compared to control group (CG). PR showed significant differences at short-term follow-up in asthma control and quality of life. No significant differences were observed for lung function, airway inflammation, physical activity levels, and body composition. Most studies had a high risk of bias, and the certainty of evidence was very low for some outcomes. CONCLUSIONS: . PR improved asthma control, exercise capacity, quality of life, anxiety, and depression in adults with asthma compared to CG. Nevertheless, these findings should be interpreted cautiously because of the high risk of bias, low certainty of evidence for some outcomes, and uncertainty in sensitivity analyses.

The main motor symptoms of Parkinson's disease (PD) emerge following dopamine depletion in the dorsal striatum and are associated with structural and functional adaptations of striatal medium spiny neurons (MSN). Although the indirect pathway MSN (iMSN) selectively expresses dopamine D2 receptors (D2R), the contribution of D2R signaling to these adaptations remains incompletely understood. Here, we examined neuronal morphology, dendritic spine density, corticostriatal transmission, and intrinsic excitability in direct pathway MSN (dMSN) and iMSN from constitutive D2R knockout mice, with or without chronic nigrostriatal lesions induced by 6-hydroxydopamine. D2R ablation reduced dendritic length and complexity in both MSN subtypes, although the effects were markedly greater in iMSN. In iMSN, D2R ablation also reduced spine density and increased intrinsic excitability, reproducing well known effects of nigrostriatal lesions and largely occluding additional effects of dopamine denervation. In contrast, D2R ablation produced only modest changes in dMSN spine density and excitability and did not prevent the additional spine loss and hyperexcitability induced by 6-OHDA lesions. Basal corticostriatal transmission remained largely preserved after D2R ablation in either MSN subtype, except for a slower excitatory postsynaptic current decay in iMSN, which was not enhanced further by the dopamine depleting lesion. Remarkably, nigrostriatal lesions continued to depress corticostriatal excitatory postsynaptic currents in D2R-deficient mice, indicating that this synaptic adaptation does not require D2R signaling. Together, these findings identify D2R signaling as a major determinant of iMSN structural and intrinsic physiological integrity and demonstrate that global loss of D2R function reproduces many of the adaptations induced by dopamine depletion. More broadly, they indicate that dopamine depletion drives distinct forms of plasticity through separable D2R dependent and independent mechanisms, with depression of corticostriatal synaptic currents in iMSN arising independently of D2R signaling.

Post-stroke depression (PSD) represents a complex neuropsychiatric challenge characterized by persistent neuroinflammation and synaptic dysfunction, yet effective therapeutic interventions are constrained by the blood-brain barrier (BBB) and the lack of specific targets. Using a multidimensional screening strategy for Chaihu-Jia-Longgu-Muli Decoction (CLM), we identified ginsenoside Rd (Rd) as a key blood-absorbed bioactive constituent associated with Epidermal Growth Factor Receptor (EGFR) signaling. To overcome the bioavailability bottleneck, a biomimetic nanodelivery system is engineered by encapsulating Rd into microglia-derived exosomes (Exos@Rd). Based on the reported lesion-homing properties of microglia-derived exosomes, we developed a biomimetic Exos@Rd delivery system. Exosomal loading markedly enhanced the brain accumulation of Rd compared with free Rd. Mechanistically, it is demonstrated that aberrant EGFR activation functions as an upstream regulator of the JAK2/STAT3 cascade in microglia. Exos@Rd effectively suppressed this pathway and promoted anti-inflammatory microglial reprogramming, characterized by a shift from an M1-associated pro-inflammatory state toward an M2-associated anti-inflammatory profile. This microglia-centered anti-inflammatory regulation was accompanied by reduced oxidative stress and restoration of brain-derived neurotrophic factor (BDNF), postsynaptic density protein 95 (PSD95) and Synapsin I (SYN1) expression. In a PSD mouse model, Exos@Rd significantly restores cerebral perfusion and alleviates depressive-like behaviors. Collectively, this study elucidates a novel EGFR-driven neuroinflammatory mechanism and presents a bio-inspired strategy for precision CNS drug delivery, offering a promising therapeutic paradigm for PSD.

Psychomotor retardation (PMR) is a core feature of major depressive disorder (MDD), yet its neural substrates remain elusive. We hypothesized that aberrant striato-cortical connectivity differentially underlies the cognitive and motor components of PMR. In a case-control study, 172 PMR patients, 387 non-PMR patients, and 297 healthy controls were examined using a gray matter-white matter-gray matter (G-W-G) connectivity model. The dataset was split into primary (80%) and validation (20%) sets. In both sets, the PMR group showed reduced connectivity between the left dorsolateral prefrontal cortex and bilateral ventral striatum (negatively associated with cognitive retardation), and enhanced connectivity between the right primary motor cortex and bilateral dorsal striatum (positively associated with motor retardation). These findings demonstrate that distinct striato-cortical pathways differentially contribute to PMR subcomponents, with cognitive retardation linked to disrupted cognitive control circuits and motor retardation to hyperconnectivity in motor pathways.

BACKGROUND: The purpose of this study was to examine factors associated with dental service utilization among Indonesian youth using the Expanded Andersen Behavioral Model (EABM). METHODS: This cross-sectional study assessed data from 3332 people aged 15 to 24 from the 2023 Indonesian Health Survey. Using EABM, variables were classified as predisposing, enabling, need, and psychosocial domains. Dental service utilization within the previous year was the outcome variable. A series of appropriate statistical analysis, such as chi-square, binary logistic regression, multivariable logistic regression, and principal component analysis (PCA) with varimax rotation was conducted to analyse the 2023 Indonesian Health Survey data. Logistic regressions were reported as odds ratios (ORs) with 95% confidence intervals (CIs). PCA was conducted to examine clustering patterns among the included variables and to assess whether these patterns were broadly consistent with the conceptual domains. RESULTS: Overall, only 7.6% of respondents reported using dental services within the previous year. Female (adjusted OR [AOR] [95% CI] = 1.655 [1.236-2.154]), urban residence (AOR [95% CI] = 2.274 [1.689-3.058]), and health insurance ownership (AOR [95% CI] = 1.985 [1.383-2.849]) were significantly associated with higher utilization rates. Factors that showed the strongest associations were oral pain (AOR [95% CI] = 12.630 [7.747-20.582]) and caries experience (AOR [95% CI] = 2.342 [1.467-3.741]). In contrast, psychosocial factors, including depression and psychological distress, were not significantly associated with utilization. PCA identified four components corresponding to psychosocial, need, predisposing, and enabling domains, which explained 60.24% of total variance, supporting the conceptual structure of EABM. CONCLUSION: Dental service utilization among Indonesian youth remains low and is primarily driven by clinical need and structural access factors rather than psychosocial conditions. While psychosocial variables were in line with a coherent latent construct, they did not translate into observable utilization behaviour.

Topographic depressions in karst landscapes, called dolines, serve as important microrefugia for biodiversity. However, they may be strongly affected by various anthropogenic disturbances, including forest management, waste dumping, and livestock grazing. Although the effects of grazing on doline vegetation are well documented, far less is known about how grazing intensity influences arthropod communities within these landforms. To study the effects of grazing intensity on arthropods, we applied a multi-taxa approach including spiders (Araneae), true bugs (Hemiptera: Heteroptera), and ants (Hymenoptera: Formicidae) as bioindicators. We selected 18 doline bottoms and their adjacent plateaus in the Aggtelek Karst, Hungary, and sampled them over two consecutive years - with grazing present in one year and excluded in the other, the latter serving as a control. We used structural equation models (SEMs) to assess how habitat type (doline vs. plateau) - which reflects associated differences in microclimate and vegetation characteristics - together with grazing intensity influenced arthropod abundance and diversity. The SEMs showed that in the control year, habitat-related differences between dolines and plateaus were clearly reflected in the diversity patterns of all three arthropod groups, with higher species richness and abundance in dolines. Grazing partially overrode this pattern through both direct and indirect pathways, although the extent and underlying mechanisms differed among taxa. Our results demonstrate that habitat type, vegetation height, and grazing intensity interactively shape arthropod diversity in karst landscapes. Appropriately managed grazing may help maintain the arthropod biodiversity of these microrefugia and should therefore be considered in future conservation planning.

BACKGROUND: Psychological resilience predicts better outcomes in persons with multiple sclerosis (pwMS), yet factors which sustain it over time remain poorly understood, particularly in diverse populations. Personality traits may represent stable determinants of resilience. OBJECTIVES: To examine the influence of personality on resilience in Black and Non-Hispanic White pwMS (BpwMS/WpwMS) and their healthy counterparts (BHCs/WHCs). METHODS: Psychological resilience and personality were assessed in a matched cohort of 120 pwMS and 80 HCs using the Connor-Davidson Resilience Scale and NEO-Five Factor Inventory-3. Personality and resilience were compared across groups. In pwMS, cross-sectional regression and longitudinal mixed-effects models evaluated personality-resilience associations; sensitivity analyses adjusted separately for depressive symptoms, psychiatric history, and subjective social status to evaluate the robustness of these associations. RESULTS: PwMS and HCs reported similar levels of Neuroticism, Agreeableness, and Conscientiousness; Extraversion and Openness were lower in pwMS. PwMS had worse resilience compared to HCs at follow-up. Higher Neuroticism predicted lower resilience, with a stronger association observed in BpwMS; higher Extraversion and Conscientiousness predicted better resilience. Higher Conscientiousness was associated with less longitudinal decline in resilience. Adjustment for depression attenuated the Conscientiousness and Neuroticism × Race associations, whereas Neuroticism and Extraversion associations remained significant. In prospective models, Conscientiousness continued to predict follow-up resilience independent of baseline depression. CONCLUSIONS: Personality traits may identify pwMS susceptible to reduced psychological resilience; Conscientiousness in particular may help sustain it over time. Although depression contributes to personality-resilience relationships, Neuroticism and Extraversion remain independently associated with resilience. Our findings support personality-informed approaches to strengthen psychological resilience in pwMS and identify depression as a clinically actionable target for future intervention.

Metabotropic glutamate receptor subtype 5 (mGlu5) is an important regulator of excitatory neurotransmission and remains a therapeutic target for neuropsychiatric and neurological disorders, including substance use disorders, depression, Fragile X syndrome, Parkinson's disease-related dyskinesia, and other movement disorders. However, the clinical development of mGlu5 negative allosteric modulators (NAMs) has been limited by translational challenges, inconsistent efficacy, and safety concerns, particularly hepatotoxicity associated with early acetylene-containing scaffolds such as ADX10059. The study provides an updated assessment of the mGlu5 NAM patent landscape and related medicinal chemistry advances from 2018 to the present. The post-2018 period is characterised as a phase of translational and medicinal chemistry refinement, marked by a shift from metabolically unstable aryl-alkyne and acetylene-based chemotypes towards more stable heterocyclic, bicyclic, and non-acetylene frameworks. Key strategies include scaffold hopping, structure-based drug design, receptor occupancy assessment, and pharmacokinetic optimisation to reduce the risk of bioactivation, improve brain exposure, and enhance clinical translatability. Recent patent-linked compounds such as TMP-301/HTL0014242, VU0424238, VU6031545, VU6024945, and AE90015 are presented alongside unconventional approaches, including GET-73, LCGM-10, antibodies, and nanobodies. It also covers clinical progress, including the repurposing of mavoglurant/STP7 for cocaine use disorder. Overall, the field aims for safer, more selective, and better-controlled mGlu5 modulation strategies, but challenges related to efficacy, tolerability, and patient selection continue to hinder clinical success.

AIMS: Few studies have examined menopause's impact on health outcomes in women living with Type 1 diabetes mellitus (T1D). We compared physical, diabetes-related, and psychosocial outcomes between premenopausal and postmenopausal women with T1D. METHODS: A cross-sectional analysis of 211 women aged 40-60 years from the BETTER registry (121 premenopausal; 90 postmenopausal). Outcomes included physical complications (retinopathy, neuropathy, cardiovascular disease [CVD], falls), diabetes management (HbA1c, insulin doses, hypoglycemia, medication), and psychosocial outcomes (depressive symptoms, fear of hypoglycemia [FOH]). Overlap weighting balanced covariates between groups; weighted regression models estimated associations as risk ratios (RR) for binary and mean differences (MD) for continuous outcomes (95% CI). RESULTS: In weighted models, postmenopausal women had higher risks of CVD (RR 3.31 [1.07-10.23]), neuropathy (RR 2.22 [1.17-4.21]), retinopathy (RR 2.20 [1.15-4.23]), falls (RR 2.64 [1.73-4.03]), and moderate-to-severe depressive symptoms (RR 1.48 [1.01-2.17]), and lower odds of antihypertensive (RR 0.57 [0.38-0.84]) and lipid-lowering prescriptions (RR 0.68 [0.54-0.86]), and elevated diabetes distress (RR 0.80 [0.68-0.95]). Insulin doses, HbA1c, hypoglycemia frequency, and FOH did not differ. CONCLUSIONS: Postmenopausal women with T1D showed less favourable physical and psychosocial health profiles than premenopausal women, underscoring the need for prospective studies to clarify these associations.

Adults with schizophrenia spectrum disorders (SSDs) have substantially elevated suicide risk, yet few suicide prevention interventions have been developed or tested for this population. The effectiveness of Cognitive-Behavioral Suicide Prevention for psychosis (CBSPp) in US community mental health (CMH) settings remains unknown. This study aimed to examine the preliminary effectiveness of the CBSPp intervention in reducing suicidal ideation, depressive symptoms, psychosis symptoms, and emergency/hospital service use compared with services as usual (SAU) among adults with SSDs in a CMH setting. A pilot randomized clinical trial was conducted between 2022 and 2025 with four assessment timepoints. Adults aged 18 years or older receiving CMH services who met DSM-5 criteria for an SSD and reported suicidal ideation or attempt within 12 months of screening. Fifty-one participants were randomized (CBSPp + SAU, n = 25; SAU, n = 26) and forty-one (80.4%) completed the final follow-up assessment. Primary outcomes were assessed with the Columbia-Suicide Severity Rating Scale, Calgary Depression Rating Scale for Schizophrenia, Positive and Negative Syndrome Scale, and electronic health records. Analyses followed the intention-to-treat principle. Among participants (mean [SD] age, 44.5 [12.9] years; 31 male [60.8%]), significant group × time interactions were observed for suicidal ideation severity (F(3,125.25) = 3.48; P = .018; η ≈ 0.10), depressive symptoms (η ≈ 0.07), negative psychosis symptoms (η ≈ 0.12), and general psychosis symptoms (η ≈ 0.17), indicating greater reductions among participants receiving CBSPp compared with SAU. Preliminary findings provide support for further evaluation of CBSPp in larger, adequately powered trials across diverse clinical settings to establish its effectiveness and impact on suicide-related outcomes among adults with SSDs.

BACKGROUND: Herpes zoster (HZ) has been linked to elevated cardiovascular risk, but the mechanisms remain unclear. Depressive symptoms, particularly specific domains of symptoms, may show statistical mediation in this association. This study examined the longitudinal association between HZ and heart disease, assessed whether depressive symptoms showed statistical mediation, and conducted exploratory internal prediction analyses using machine-learning survival models. METHODS: Based on the data from the Health and Retirement Study (HRS), we used Cox proportional hazards models to estimate the association between HZ and heart disease and mediation analyses to evaluate the role of total, cognitive-affective, and somatic depressive symptoms in middle-aged and older adults. In addition, five survival prediction models, including Cox, RSF, GBM, LASSO-Cox, and XGBoost, were evaluated using the concordance index (C-index). RESULTS: Among 16,195 participants, HZ was associated with an increased risk of heart disease (adjusted HR 1.22, 95% CI 1.09-1.38, P = 0.001). Significant statistical indirect effects were observed for total (P = 0.003) and somatic depressive symptoms (P = 0.001), whereas no significant indirect effect was observed for cognitive-affective symptoms. Among the evaluated models, Cox and LASSO-Cox showed the highest discrimination, with C-indices of approximately 0.67. CONCLUSION: HZ was associated with an increased risk of incident heart disease. Statistical indirect effects were observed through depressive symptoms, particularly somatic symptoms, under the assumed temporal ordering. HZ and depressive symptoms provided modest additional predictive information in exploratory internal analyses.

STUDY OBJECTIVES: To determine the effect of CPAP therapy on symptom burden in OSA patients with and without type D personality. METHODS: OSA patients eligible for CPAP treatment filled out the DS-14, BFI-2, HADS, SF-36, PSQI, ISI, ESS, SSS, FAS and CIS questionnaires. These were repeated at 3, 6 and 18mo after CPAP initiation. At each visit, adherence and residual AHI were collected from the CPAP device. RESULTS: Of the 605 patients who initiated CPAP treatment for moderate to severe OSA and were included in the study, 384 patients showed optimal CPAP treatment (residual AHI <5/hour combined with an adherence of ≥ 4h/night) at visit 1, and 272 patients completed all study visits with optimal CPAP treatment during the entire 18 months follow-up period. CPAP therapy had a positive impact on fatigue, anxiety, depression, health perception, sleepiness, sleep quality, and insomnia severity at 3 months, with an additional improvement of the latter 3 symptoms at 6 months. Despite these improvements, OSA patients with type D personality remained significantly more symptomatic at 18 months. CONCLUSION: While OSA patients benefit from CPAP treatment, irrespective of type D personality, the patients with type D do show more residual OSA symptoms than their non-type D counterparts. These results suggest close and pro-active management could be relevant in patients with OSA and type D personality.

STUDY OBJECTIVES: Poor sleep is linked to adverse health outcomes. Animal studies suggest the gut microbiome may influence sleep, but human findings remain inconsistent. We examined associations of self-reported insomnia symptoms, daytime sleepiness, and actigraphy-measured sleep with gut microbiome diversity and composition in older adults. METHODS: We studied 869 Baltimore Longitudinal Study of Aging participants with self-reported sleep and shotgun metagenomic sequencing; 332 also had actigraphy. We tested associations of sleep with alpha diversity, beta diversity, and species composition using regression, PERMANOVA, and ANCOM-BC2, adjusting for age, sex, BMI, physical activity, education, and depressive symptoms. RESULTS: Participants had mean age 70.7 years; 54.8% were female and 66.9% White. Trouble falling asleep ≥5 times/week was associated with higher Shannon diversity (β=0.41 SD; 95% CI: 0.09, 0.73) and Pielou's evenness, but not richness metrics. No actigraphy-measured sleep variables were associated with alpha or beta diversity. Beta diversity analyses suggested excessive sleepiness (1-2 o 3-4 times/week) was associated with different microbial composition, though variance explained was small. In species-level analyses, frequent insomnia symptoms or excessive sleepiness were associated with depleted or undetected Eubacterium sp. CAG:251. In exploratory actigraphy models, each doubling of sleep efficiency was associated with higher Eubacterium sp. CAG:251 prevalence (PR=2.15; 95% CI: 1.47, 3.14), while each 30-minute increase in wake after sleep onset was associated with lower prevalence (PR=0.49; 95% CI: 0.29, 0.81). CONCLUSIONS: Global diversity findings were limited and inconsistent, whereas subjective and objective sleep disturbances converged on Eubacterium sp. CAG:251. Findings are exploratory and require longitudinal replication.

BackgroundAlthough neuropsychological scores have predicted progression from mild cognitive impairment (MCI) to dementia, past work has limitations, including small samples, limited batteries, and research cohorts.ObjectiveThis study sought to identify which baseline cognitive scores predicted progression in clinical patients with MCI followed over 1.5 years.Methods243 individuals clinically diagnosed with MCI at a baseline visit completed neuropsychological testing at baseline and were followed approximately 1.5 years later. Using follow-up diagnoses from neurologists, they were grouped as "MCI-Stable" (i.e., MCI at baseline and follow-up, n = 131) or "MCI-Progressors" (i.e., MCI at baseline but dementia at follow-up, n = 112). Stepwise logistic regression examined follow-up group status predicted from demographics, baseline cognitive scores, and self-reported depressive symptoms.ResultsNeither baseline demographic variables nor depressive symptoms significantly predicted group status at follow-up. Conversely, worse baseline performance on tests of visuospatial construction and semantic fluency were significant predictors of progression from MCI to dementia. Longer follow-up interval also significantly predicted conversion.ConclusionsAlthough many individuals progress from MCI to dementia, there is considerable variability in the timing and cognitive performance among those who convert to dementia versus those who remain stable over time. The current findings identified multiple baseline neuropsychological test scores that predicted that progression over approximately 1.5 years. Such results have implications for clinical care (e.g., providing more services and closer monitoring of at-risk individuals) and research (e.g., enriching clinical trials with those more likely to progress).

BackgroundMeaningful employment is essential to recovery, self-esteem, and life satisfaction for individuals with traumatic brain injuries (TBIs), particularly those who are high-functioning. Engagement in purposeful work can foster emotional and functional gains during rehabilitation.ObjectiveThis single-case retrospective study explored how meaningful employment impacted one client with TBI and examined how transportation barriers limited access to work.MethodsData were collected from December 2022 through March 2023 using the Canadian Occupational Performance Measure, Beck Depression Inventory, and daily SOAP notes during a three-month occupational therapy intervention.ResultsThe client showed significant improvements in mood, occupational performance, and satisfaction when supported in accessing meaningful work.ConclusionsOccupational therapists and interdisciplinary teams play a critical role in facilitating vocational engagement. Structural transportation barriers should be addressed as part of rehabilitation planning to support access to meaningful employment, overall well-being, and long-term community participation.

INTRODUCTION: Caregivers have first-hand experience of facing the daily challenges of Rett syndrome (RTT). The aim of this study was to understand caregivers' experiences of RTT, including challenging symptoms that caregivers hope novel therapies will address. METHODS: This non-interventional, qualitative and quantitative market research study engaged caregivers of individuals with RTT in the USA, the UK, Canada, and Israel, through an online survey comprising both closed- and open-ended items. Survey domains included age of symptom onset, symptom severity and impact on quality of life, the most challenging symptoms, and caregiver perspectives on meaningful improvement. RESULTS: A total of 323 caregivers completed the survey. Symptoms with the most severe and lasting impact on patients' quality of life typically presented by 6 years of age. These symptoms included loss of speech, loss of purposeful use of hands, and gait disturbances. Caregivers reported a dynamic and lifelong burden associated with impairments in activities of daily living and expressed a desire for improvement across these functional domains following gene therapy treatment. CONCLUSION: Despite RTT's clinical heterogeneity, similarities emerged in caregivers' daily experiences and their hopes regarding gene therapy treatment. Caregivers believe meaningful improvements for people with RTT would be improved function and enhanced autonomy related to fine and gross motor abilities, and improved ability to communicate needs.