CSA is associated with post-traumatic stress disorder (PTSD), dissociation, emotion-regulation difficulties and psychopathology. Trauma-focused cognitive behavioral therapy (TF-CBT) and eye movement desensitization and reprocessing (EMDR) are evidence-based interventions, but their sequential delivery in online groups for women with CSA-related complex trauma remains underexplored.

To examine feasibility and preliminary clinical outcomes of a 16-session online group intervention combining TF-CBT and EMDR Group Traumatic Episode Protocol (G-TEP), and to explore differences by sequence (EMDR → CBT vs. CBT → EMDR).

Of 31 eligible participants, nine adult women (Mean age = 39.42 years, SD = 10.23) completed both phases and assessment (EMDR → CBT: n = 5; CBT → EMDR: n = 4). Assessments at baseline (T1), T2, and T3 included PTSD (EGS-R), dissociation (DES), psychopathology (SCL-90-R), emotion regulation (DERS), self-esteem (RSES), life satisfaction (SWLS), and treatment satisfaction (CRES-4). Non-parametric tests and effect sizes were used. An illustrative case was included.

The intervention showed descriptive improvements across domains, including PTSD symptoms, dissociation, and psychopathology, with improved self-esteem and life satisfaction. However, most statistical tests were non-significant, consistent with the exploratory nature of the small sample. Effect sizes indicated variability across sequences: EMDR → CBT showed larger effects in phobic anxiety and self-esteem, whereas CBT → EMDR showed larger effects in dissociation. Findings indicate exploratory sequence-related patterns rather than definitive treatment effects.

Sequential online delivery of TF-CBT and EMDR G-TEP appears feasible among completers, although substantial attrition limits feasibility. Findings are preliminary and require confirmation in future controlled studies.

3q29 deletion syndrome is a rare genomic disorder characterized by a broad spectrum of neurodevelopmental and psychiatric manifestations, including developmental delay (DD), intellectual disability (ID), autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and a markedly increased lifetime risk of psychosis and schizophrenia.

We describe a 17-year-old female adolescent with severe congenital heart disease and longstanding neurodevelopmental impairment who developed early-onset recurrent psychotic symptoms. Chromosomal microarray analysis identified a de novo heterozygous 1.6 Mb deletion at the 3q29 locus. The emergence of psychotic symptoms served as the pivotal clinical trigger for genetic investigation in the absence of distinctive dysmorphic findings. Combination therapy with lurasidone and olanzapine led to sustained clinical stabilization over a one-year follow-up period, allowing gradual dose adjustment and functional reintegration through adapted educational and recreational activities.

Early-onset psychotic symptoms in adolescents with neurodevelopmental comorbidities may represent a critical clinical indicator of underlying pathogenic copy number variants, including 3q29 deletion syndrome, even in the absence of highly recognizable dysmorphic features. Increased clinical awareness may facilitate consideration of early genetic testing in this clinical profile to support precision-informed diagnostic evaluation, treatment planning and multidisciplinary management.

Large language models have evolved from laboratory demonstrations into mass-market companion-style conversational agents that many users treat as social partners. As these systems produce increasingly human-like conversational behavior, users may attribute mind, form affective bonds, disclose sensitive information, and rely on agents for emotional support, creating both potential benefits and psychosocial risks.

We conducted a PRISMA-ScR-informed scoping review of socioaffective human-artificial intelligence interaction research published or posted from 2016 to 15 January 2026. Eligible sources addressed companion-style conversational agents and adjacent therapeutic, assistant-first, or governance sources. Evidence was stratified by system type and calibrated as stronger empirical support, moderate support, preliminary support, or proposed/normative synthesis.

The final evidence map included 58 sources. We synthesized mechanisms that make agents feel social, including anthropomorphism, social presence, mind perception, self-disclosure, parasocial attachment, and socioaffective alignment. Therapeutic chatbot studies provided the strongest evidence for short-term symptom reduction in selected contexts, whereas evidence for sustained loneliness reduction in open-domain companion systems remained emerging. Reported and hypothesized risks included dependency-like use, displacement of human interaction, maladaptive validation or sycophancy, persuasive manipulation, privacy harms, and risks to minors or vulnerable users.

We propose an integrative pathway linking model capabilities and product design cues to relational outcomes and outline a companion-specific relational safety stack as a synthesis-based evaluation agenda rather than a validated regulatory or clinical standard. The review identifies measurement priorities for evaluating companion agents and governance priorities for managing psychosocial impact as these systems scale.

Neuroinflammation is recognized as a pivotal pathological process underlying a spectrum of neurological disorders. The exploration of natural flavonoids as therapeutic agents has substantially advanced our understanding of strategies to mitigate neuroinflammatory injury. Accumulating evidence indicates that kaempferol-a dietary flavonoid abundantly present in various fruits and vegetables-exerts potent neuroprotective effects in multiple neurological conditions. Its beneficial actions are mediated through multi-target mechanisms, primarily involving the suppression of microglial activation, modulation of immune cell reactivity, and enhancement of endogenous antioxidant defenses. These mechanisms collectively contribute to reduced production of inflammatory mediators, alleviation of oxidative stress, and inhibition of neuronal apoptosis, thereby counteracting the pathogenesis of various neuroinflammatory diseases. This review summarizes current knowledge on the protective role of kaempferol in the pathogenesis and progression of central nervous system disorders. We further elucidate the underlying molecular and cellular mechanisms, as well as autophagy and oxidative stress. Additionally, potential challenges in clinical translation, such as bioavailability and blood-brain barrier permeability, are discussed to guide future research in this promising field. Elucidating the pleiotropic actions of kaempferol will not only deepen our understanding of its pharmacodynamics but may also open new avenues for the prevention and treatment of neuroinflammatory-related neurological diseases.

Demoralization, a syndrome of helplessness, hopelessness, and loss of meaning and chronic pain are common sources of distress in early palliative care. Psilocybin-assisted therapy (PAT) is an emerging intervention with preliminary data suggesting improvements in pain and demoralization. To date, PAT has not been studied among people living with both demoralization and chronic pain nor has it been studied as part of routine multidisciplinary outpatient palliative care.

We conducted an open-label pilot study assessing the safety, feasibility, and acceptability of PAT delivered with multidisciplinary palliative care support in cancer patients across the illness trajectory living with demoralization and chronic pain.

Participants received a single 25 mg oral dose of psilocybin with preparation, monitoring, and integration provided by a mental health clinician and spiritual health clinician, alongside multidisciplinary palliative care support. Outcomes included safety, feasibility, acceptability, and exploratory self-report measures assessing for demoralization and pain intensity pre- and post-dosing.

Eleven participants were enrolled, ten of whom received psilocybin. The intervention was safe and feasible, with no serious adverse events and complete study visit retention among dosed participants. All 10 dosed participants reported the intervention as highly acceptable. Among dosed participants, 70% rated the experience among the five most meaningful and educational of their lives, and 60% among their five most spiritually significant experiences. By study endpoint, 90% no longer met criteria for clinically-significant demoralization syndrome and had pain scores below the trial enrollment threshold.

PAT delivered with multidisciplinary palliative care support was safe, feasible, and acceptable in demoralized cancer patients with chronic pain.

Psilocybin-assisted therapy delivered within multidisciplinary outpatient palliative care was safe, feasible, and acceptable among demoralized cancer patients with chronic pain.

Electronic health record (EHR)-linked biorepositories provide opportunities to advance epidemiological research in Alzheimer's disease (AD) and related dementias.

Evaluate the extraction, curation, and associative validity of Mini Mental State Examination (MMSE) scores from the VA EHR for participants in the VA Million Veteran Program (MVP).

The sample (N = 49,555; 7.4% women) included a multiethnic cohort (European [68.3%], African [20.4%], Hispanic [9.0%]) with EHR-extracted MMSE scores; 30.7% were apolipoprotein E ( APOE ) ε4 carriers, and 25.8% had multiple scores. Linear regressions examined cross-sectional associations between ε4 dosage (0, 1, 2) and first and lowest MMSE scores. MMSE scores were also evaluated against MVP dementia diagnostic algorithms in participants aged ≥65 years.

Among participants of European ancestry, there was a significant ε4 dose-response relationship ( p s < .001) with MMSE scores. Homozygote carriers scored lower than heterozygote carriers (M _diff : first = -0.5; lowest = -0.9), who scored lower than non-carriers (M _diff : first = -0.4; lowest = -0.6). Among Veterans of African and Hispanic ancestry, no dose-response relationship was observed, although ε4 carriers had lower scores than non-carriers ( p s ≤ .04). MMSE scores corresponded strongly with dementia case/control status across phenotypes: mild impairment on the MMSE was strongly associated with AD (odds ratio [OR] = 11.48), with more severe MMSE impairment showing stronger associations (moderate OR = 17.95; severe OR = 27.83).

This study demonstrated MMSE scores can be systematically extracted and curated from the VA EHR. Findings offer a scalable framework for future studies on risk stratification, highlighting the potential for harnessing MVP to explore genetic and clinical factors contributing to cognitive and dementia outcomes in diverse samples.

There is a bidirectional relationship between emotional distress and pain. However, this relationship is understudied in people with HIV in low-resource settings. This study sought to describe the temporal relationship between emotional distress and pain in people with HIV.

Longitudinal observational study.

Participants with virally suppressed HIV, reporting either no pain or persistent pain at baseline, provided weekly remote ratings of distress, worst pain, and average pain using 0-10 visual analogue scales. Within-individual fluctuations in distress and pain were visualised over time. Group-level correlations were determined using Spearman's correlation tests. Cumulative link mixed models assessed whether distress and pain each predicted the other in the following week.

72 participants provided responses over 49 weeks. The participants had a median (IQR) age of 43 (37-51) years, 63% (n=45) were unemployed and most were females (n=51;71%). Distress and pain fluctuated concurrently within individuals: distress was positively correlated with worst pain (ρ=0.66, 95% CI= 0.60-0.72, p<0.001) and average pain (ρ=0.70, 95% CI=0.64-0.75, p<0.001) intensity within the same week. Worst pain (OR=1.42, 95% CI=1.17-1.71, p<0.001) and average pain (OR=1.43, 95% CI=1.20-1.71, p<0.001) intensity both predicted distress in the next week. Distress predicted worst pain intensity (OR=1.25, 95% CI=1.07-1.46, p=0.023) but not average pain intensity (OR=1.19, 95% CI=1.01-1.40, p=0.152) in the next week.

The temporal relationship between distress and worst pain intensity was bidirectional, whereas distress did not temporally predict average pain intensity. Both pain and emotional distress should receive attention from HIV research and clinical care in low-resource settings.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been linked to heterogeneous, potentially pleiotropic effects across organ systems, motivating outcome-wide comparative risk profiling in real-world data. A central challenge in such analyses is residual bias that remains after adjustment for observed confounders, which can distort effect estimates and mis-calibrate uncertainty. We present distributional diagnosis and calibration (DC), which uses panels of negative control outcomes (NCOs) to diagnose residual bias and calibrate uncertainty. DC evaluates null behavior via p -value uniformity and empirical coverage across NCOs, and uses the empirical distribution of NCO effect estimates to calibrate confidence intervals for prespecified primary outcomes. DC is modular: it can wrap around commonly used causal inference methods and operates directly on summary statistics, supporting collaborative research under data-sharing constraints. Using electronic health records from a large U.S. clinical research network (152.7 million patients), we compared GLP-1RAs with sodium-glucose cotransporter 2 inhibitors across 15 prespecified outcomes spanning cardiovascular, mental health, and genitourinary domains using four causal estimators. Across outcomes and methods, DC diagnostics revealed substantial and method-dependent residual systematic error. DC calibration attenuated systematic error signals observed in negative controls and yielded more stable, better-calibrated estimates for clinical outcomes, supporting DC as a practical strategy to strengthen the credibility of outcome-wide real-world CER.

The contents are solely the responsibility of the authors and do not necessarily represent the official views of, or an endorsement by, Food and Drug Administration (FDA)/Department of Health and Human Services (HHS) or the U.S. Government.

Policy Points The federal government should provide states with authorities under Medicaid that allow greater use of home and community-based services for people with serious and persistent mental illness. This requires deemphasizing authorities that require budget neutrality in a post-institutionalization world (Section 1115 waivers) and relying on those with greater budget flexibility (Section 1915 waivers). The federal government, in its design of new mental health programming, would make it most effective if it establishes regulations and oversight that permit states to effectively pursue policy intents. When federal programs that intend to deal with consequences of serious and persistent mental illness are provided through broad authorities (e.g., 988 call lines), states should take greater care to create expectations and lines of accountability that align with federal intent and limit tendencies toward mission drift.

Since the early 1960s, US policymakers have sought to assist persons living with intellectual and developmental disabilities (IDDs) and persons living with severe and persistent mental illness (SPMI) to live on a human scale with their clinical and service needs met in their communities.

We review this history, including the accomplishments and shortcomings of these efforts.

People with both sets of disabilities and their families have benefited from deinstitutionalization. Yet deinstitutionalization proved tangibly more successful in assisting people with IDDs and their families than have comparable efforts that sought to assist people with SPMI and their families.

These contrasting histories offer instructive lessons for state policymakers and others seeking to improve services for people living with SPMI.