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.

Advances in pediatric oncology have created a growing cohort of adult survivors of childhood cancer, but data on long-term psychological outcomes from low- and middle-income countries (LMICs) remain limited. We evaluated psychosocial outcomes among adult survivors of childhood cancer in North India and examined demographic and clinical predictors of distress, social support, self-esteem, and sexual dysfunction.

In this cross-sectional study at a tertiary care cancer center in India, 266 long-term survivors diagnosed at ≤21 years of age, aged ≥18 years at recruitment, who had completed definitive therapy and remained cancer-free for ≥2 years, underwent psychological assessment using the HADS, MSPSS, SRQ, RSS, and SDQ.

Overall, 62.1% screened positive for borderline/abnormal anxiety symptoms and 82.2% for borderline/abnormal depressive symptoms. Despite this burden, 87.9% reported high perceived social support. Mental distress and low self-esteem were reported by 16.9% and 5.9%, respectively. Among 120 sexually active respondents, 70.8% screened positive for sexual dysfunction. Female sex was independently associated with higher anxiety, higher mental distress, and lower perceived social support. Time off therapy less than 8 years was associated with lower self-esteem. Diagnosis at age ≤12 years was associated with greater sexual dysfunction.

Adult survivors of childhood cancer experience a substantial and partly hidden psychosocial burden, and their psychological journey is influenced not just by biology, but by the deep-rooted cultural norms and societal structures. The current study offers valuable evidence from India, with implications for survivorship care across LMICs.

This study aimed to examine college students' trust in generative artificial intelligence (AI) for mental health information and decisions.

Among 926 undergraduates at two institutions in the 2024-2025 Healthy Minds Study, demographic and clinical correlates of dichotomized trust ratings were examined.

Overall, 31% trusted AI for mental health information, and 13% trusted AI for mental health decisions. Severe depression, anxiety, and therapy history were not significantly associated with trust. Students with (vs. without) a lifetime psychiatric diagnosis trusted AI less for information (28% vs. 34%). Lesbian, gay, bisexual, and queer (LGBQ; vs. non-LGBQ) students trusted AI less for information (21% vs. 38%) and decisions (7% vs. 17%). International (vs. domestic) students trusted AI more for information (52% vs. 29%), and Asian (vs. White) students trusted AI more for decisions (17% vs. 11%).

Trust varied by identity but not by most clinical characteristics. Clinicians should ask patients about AI use.

Adolescence is characterized by heightened emotional reactivity and rapid maturation of emotion regulation (ER) capacities. Sexual abuse during adolescence disrupts normal ER development. Adolescents often struggle to modulate intrusive memories, hypervigilance, and intense affect following sexual abuse, resulting in increased distress and maladaptive coping strategies, including non-suicidal self-injury.

Using an embedded mixed-methods design, emotional dysregulation and mental health outcomes among sexually abused adolescents were examined. Three focused group discussions with 18 professionals and 43 key interviews with 25 adolescents (14 with penetrative abuse, including 1 gang rape case, and 11 with non-penetrative abuse) and 18 parents/caregivers (N = 61) were conducted at child-care institutions and hospital settings. Thematic frequency analysis resulted in 572 codes, 38 subthemes/subdomains, and 6 themes/domains across the three sample groups. Multi-informant perspectives and multiple settings were considered to draw more generalizable conclusions. Screening measures, namely the Patient Health Questionnaire-9 (PHQ-9), Screen for Child Anxiety Related Emotional Disorders (SCARED), and the Children's Revised Impact of Event Scale (CRIES-13), were used. Qualitative data focused on emotional impact, triggers, relational difficulties, academic consequences, and coping strategies, while quantitative data assessed depressive, anxiety, and post-traumatic stress symptoms.

Across all groups, themes converged on persistent emotional pain, somatic and affective reactivity, hypervigilance, mistrust in relationships, academic decline, and self-harm. Adolescents consistently reported profound emotional dysregulation, including fear, persistent crying spells, anger outbursts, and social withdrawal. Parents highlighted mood volatility, anger, withdrawal, and emotional numbing, whereas professionals identified chronic dysregulation and attachment ruptures as enduring sequelae of abuse. All adolescents scored above the cutoff on the PHQ-9, while 14 scored above the cutoff on the SCARED, and 13 on the CRIES-13.

The effects of sexual abuse type, gender differences, parental support, and the obtained themes are discussed in the context of impact severity and ER.