BMC Medicine最新文献

Background: Despite the well-documented immune dysregulation in both psoriasis and Sjögren's syndrome (SS), the specific link between these two autoimmune diseases has not been extensively explored. The present study aims to investigate the impact of psoriasis on the risk of SS.

Methods: A retrospective cohort study using TriNetX data compared SS development in patients with psoriasis and controls using propensity score matching, Kaplan-Meier curves, and Cox models. Transcriptome data were analyzed to identify shared differentially expressed genes and pathways between the two diseases.

Results: A total of 293,905 patients with psoriasis and an equal number of individuals without psoriasis were included. After propensity score matching, the baseline characteristics of both groups were balanced. During the follow-up period, 3339 patients with psoriasis and 1937 individuals without psoriasis developed SS. The Kaplan-Meier curves indicated a significantly higher risk of developing SS in the psoriasis group compared to the non-psoriasis group. Upon adjustment for multiple confounding factors, the risk of developing SS in the psoriasis group was 50% higher in the psoriasis group than the non-psoriasis group (hazard ratio [HR] 1.50, 95% confidence interval [CI] 1.42-1.58). Subgroup analyses confirmed the elevated risk of SS associated with psoriasis. Patients with psoriatic arthritis (PsA) and those treated with biological agents had an even higher risk of developing SS. Transcriptomic analysis revealed potential shared pathogenesis of psoriasis and SS involving cellular proliferation, immune cell recruitment, cytokine secretion, and the interferon response to viral infections.

Conclusions: Psoriasis might increase the risk of developing SS, which is augmented by PsA. The overlapping immunological mechanisms may underlie the co-occurrence of psoriasis and SS.

Background: Adverse life experiences have been associated with increased susceptibilities to psychopathology in later life. However, their impact on psychological responses following physical trauma remains largely unexplored.

Methods: Based on the China Severe Trauma Cohort, we conducted a cohort study of 2937 patients who were admitted to the Trauma Medical Center of West China Hospital between June 2020 and August 2023. Adverse life experiences, including childhood maltreatment (5 subtypes, measured by Childhood Trauma Questionnaire-Short Form) and adverse lifetime experiences (17 subtypes, by Life Events Checklist) were assessed. Generalized linear mixed models were used to examine the associations of childhood maltreatment and adverse lifetime experiences with symptoms of psychopathology measured at multiple time-points after the index injury (i.e., at recruitment, 1-, 3-, 6-, and 12-month follow-ups), adjusted for important confounders. We further stratified the analyses by level of genetic predisposition to a given psychological symptom quantified by polygenic risk score (PRS) based on publicly available GWAS summary statistics. Mediation analyses were performed to assess the role of adverse lifetime experiences in connecting childhood maltreatment and post-injury psychopathology.

Results: The mean age of participants was 47.95 years with a predominance of males (61.39%). During the whole follow-up period, the incidence of symptoms of stress-related disorders, anxiety, and depression was 13.86%, 29.89%, and 36.57%, respectively. We observed associations between the cumulative number of those studied adversities and increased risk of post-injury psychopathology, particularly stress-related disorder (odds ratio [OR] = 2.78, 95% confidence interval [CI] 1.87-4.12 for ≥ 2 vs no childhood maltreatment; 2.65 [1.67-4.20] for ≥ 4 vs 0-1 adverse lifetime experiences). By subtype, positive associations were observed for most studied life adversities, with the most pronounced estimates for childhood emotional abuse (ORs = 1.71-2.52) and lifetime life-threatening illness/injury (ORs = 1.87-2.89). We found basically comparable estimates among traumatized individuals with different PRSs for studied psychopathology. Moreover, adverse lifetime experiences may partially (mediation proportion: 22.52-27.48%) explain the associations between various childhood maltreatment and post-injury psychopathology.

Conclusions: Both childhood maltreatment and adverse lifetime experiences were associated with post-injury psychopathology, irrespective of genetic susceptibility. Such findings highlight the importance of close surveillance and timely psychological interventions for injury patients with adverse life experiences.

Background: Since older adults spend significant time in their neighborhood environment, environmental factors such as neighborhood socioeconomic disadvantage, high racial segregation, low healthy food availability, low access to recreation, and minimal social engagement may have adverse effects on cognitive function and increase susceptibility to dementia. DNA methylation, which is associated with neighborhood characteristics as well as cognitive function and white matter hyperintensity (WMH), may act as a mediator between neighborhood characteristics and neurocognitive outcomes.

Methods: In this study, we examined whether DNA methylation in peripheral blood leukocytes mediates the relationship between neighborhood characteristics and cognitive function (N = 542) or WMH (N = 466) in older African American (AA) participants without preliminary evidence of dementia from the Genetic Epidemiology Network of Arteriopathy (GENOA).

Results: For a 1-mile buffer around a participant's residence, each additional fast food destination or unfavorable food store with alcohol per square mile was nominally associated with a 0.05 (95%CI: 0.01, 0.09) and a 0.04 (0.00, 0.08) second improvement in visual conceptual tracking score, respectively. Also, each additional alcohol drinking place per square mile was nominally associated with a 0.62 (0.05, 1.19) word increase in delayed recall score, indicating better memory function (all p < 0.05). Neighborhood characteristics were not associated with WMH. We did not find evidence that DNA methylation mediates the observed associations between neighborhood characteristics and cognitive function.

Conclusions: The presence of fast food destinations and unfavorable food stores with alcohol was associated cognitive measures, possibly due to greater social interaction provided in these venues. However, replication of these findings is necessary. Further examination of the potential pathways between the neighborhood environment and cognitive function/WMH may allow the development of potential behavioral, infrastructural, and pharmaceutical interventions to facilitate aging in place and healthy brain aging in older adults, especially in marginal populations that are most at risk.

Background: Dutch adolescents predominantly purchase unhealthy snacks in supermarkets, which negatively influence their health. The aim of this study was to investigate the short- and longer-term effects of a nutrition peer-education intervention in supermarkets on food purchases and determinants of food purchase behaviour among adolescents of different education levels.

Methods: We performed a quasi-experimental study in three supermarkets (two intervention and one comparison school) in Amsterdam, the Netherlands. The intervention schools received a 45-min peer-education workshop in the supermarket near their school, and the comparison school received no intervention. The workshops also included a 2-week 'healthy snacking challenge' and were led by two young supermarket employees. Measurements were performed 2 weeks before the intervention (T0) 2 weeks after (T1) and 3 months (T2) after the intervention. Cash receipts were used to examine food purchases (n = 458) and questionnaires to examine determinants of food purchase behaviour (n = 463).

Results: The nutrition peer-education intervention did not improve food purchases but did improve several determinants of food purchase behaviour. Adolescents from the intervention schools reported improved nutritional knowledge (β = 0.38, 95% CI: 0.04-0.72) at T1, more favourable attitudes (β = 0.21, 95% CI: 0.00-0.42) and stronger social support (β = 0.27, 95% CI: 0.02-0.53) for healthy food purchases at T2 compared to those from the comparison schools. Adolescents with a low level of education reported more short- and longer-term improvements of determinants of food purchase behaviour compared to those with a higher level of education.

Conclusions: While nutrition peer education in supermarkets did not improve adolescents' food purchases in the supermarket, determinants of food purchase behaviour did improve. The intervention was especially effective among adolescents with a low level of education. Nevertheless, to promote healthy food purchases of adolescents in supermarkets, more efforts are needed.

Background: Identifying clusters of multiple long-term conditions (MLTCs), also known as multimorbidity, and their associated burden may facilitate the development of effective and cost-effective targeted healthcare strategies. This study aimed to identify clusters of MLTCs and their associations with long-term health-related quality of life (HRQoL) in two UK population-based cohorts.

Methods: Age-stratified clusters of MLTCs were identified at baseline in UK Biobank (n = 502,363, 54.6% female) and UKHLS (n = 49,186, 54.8% female) using latent class analysis (LCA). LCA was applied to people who self-reported ≥ 2 LTCs (from n = 43 LTCs [UK Biobank], n = 13 LTCs [UKHLS]) at baseline, across four age-strata: 18-36, 37-54, 55-73, and 74 + years. Associations between MLTC clusters and HRQoL were investigated using tobit regression and compared to associations between MLTC counts and HRQoL. For HRQoL, we extracted EQ-5D index data from UK Biobank. In UKHLS, SF-12 data were extracted and mapped to EQ-5D index scores using a standard preference-based algorithm. HRQoL data were collected at median 5 (UKHLS) and 10 (UK Biobank) years follow-up. Analyses were adjusted for available sociodemographic and lifestyle covariates.

Results: LCA identified 9 MLTC clusters in UK Biobank and 15 MLTC clusters in UKHLS. Clusters centred around pulmonary and cardiometabolic LTCs were common across all age groups. Hypertension was prominent across clusters in all ages, while depression featured in younger groups and painful conditions/arthritis were common in clusters from middle-age onwards. MLTC clusters showed different associations with HRQoL. In UK Biobank, clusters with high prevalence of painful conditions were consistently associated with the largest deficits in HRQoL. In UKHLS, clusters of cardiometabolic disease had the lowest HRQoL. Notably, negative associations between MLTC clusters containing painful conditions and HRQoL remained significant even after adjusting for number of LTCs.

Conclusions: While higher LTC counts remain important, we have shown that MLTC cluster types also have an impact on HRQoL. Health service delivery planning and future intervention design and risk assessment of people with MLTCs should consider both LTC counts and MLTC clusters to better meet the needs of specific populations.

Background: The heterogeneity of cognitive impairments in schizophrenia has been widely observed. However, reliable cognitive boundaries to differentiate the subgroups remain elusive. The key challenge for cognitive subtyping is applying an integrated and standardized cognitive assessment and understanding the subgroup-specific neurobiological mechanisms. The present study endeavors to explore cognitive subgroups and identify their morphological features.

Methods: A total of 920 schizophrenia patients and 169 healthy controls were recruited. MATRICS Consensus Cognitive Battery was applied to assess cognitive performance and recognize cognitive subgroups through latent profile and latent transition analysis. Cortical thickness and gray matter volume were employed for the morphological features across subgroups.

Results: Four reproducible cognitive subgroups were identified, including multidomain-intact, executive-preserved, executive-deteriorated, and multidomain-deteriorated subgroup. After 12 weeks of follow-up, the cognitive characteristics of three out of the four subgroups kept stability, except for multidomain-deteriorated subgroup in which 48.8% of patients with improved cognition transited into the executive-deteriorated subgroup. Across subgroups, significant gradient features of brain structure were exhibited in fronto-temporal regions, hippocampus, and insula. Compared to healthy controls, multidomain-intact subgroup showed the most intact cognition and morphology, and multidomain-deteriorated subgroup with youngest age showed morphological decline in extensive regions. The remaining two subgroups showed intermediate cognitive performance, but could be distinguished by executive function and morphological differences in posterior cingulate cortex.

Conclusions: Our study provides novel insights into the heterogeneity of cognitive impairments in schizophrenia and the morphological features from cross-sectional and longitudinal levels, which could advance our understanding of complex cognition-morphology relationships and guide personalized interventions.

Background: Dystonia is a common neurological hyperkinetic movement disorder that can be caused by mutations in anoctamin 3 (ANO3, TMEM16C), a phospholipid scramblase and ion channel. We previously reported patients that were heterozygous for the ANO3 variants S651N, V561L, A599D and S651N, which cause dystonia by unknown mechanisms.

Methods: We applied electrophysiology, Ca²⁺ measurements and cell biological methods to analyze the molecular mechanisms that lead to aberrant intracellular Ca²⁺ signals and defective activation of K⁺ channels in patients heterozygous for the ANO3 variants.

Results: Upon expression, emptying of the endoplasmic reticulum Ca²⁺ store (store release) and particularly store-operated Ca²⁺ entry (SOCE) were strongly inhibited, leading to impaired activation of K_Ca3.1 (KCNN) K⁺ channels, but not of Na⁺-activated K⁺ channels (K_Na; SLO2). The data provide evidence for a strongly impaired expression of store-operated ORAI1 Ca²⁺ influx channels in the plasma membrane of cells expressing ANO3 variants.

Conclusions: Dysregulated Ca²⁺ signaling by ANO3 variants may impair the activation of K⁺ channels in striatal neurons of the brain, thereby causing dystonia. Furthermore, the data provide a first indication of a possible regulation of protein expression in the plasma membrane by ANO3, as has been described for other anoctamins.

Background: The prevalence of autism spectrum disorder (ASD) has surged, with an estimated 1 in 36 eight-year-olds in the United States meeting criteria for ASD in 2020. Autistic individuals face elevated rates of co-occurring medical, psychiatric, and behavioral conditions compared to non-autistic individuals. The rising ASD-patient demand is increasingly outpacing the capacity of ASD-specialty clinics, resulting in urgent need for autism-competent providers in general practice settings. This work aims to empower healthcare providers, especially primary care providers (PCPs), with guidelines for the recognition and safe pharmacologic management of common co-occurring psychiatric and behavioral conditions in ASD.

Methods: Lurie Center for Autism medical providers, who have extensive experience in ASD care, delineated approaches for recognition and pharmacological treatment of sleep disturbances, attention-deficit/hyperactivity disorder (ADHD), anxiety, depression, and irritability tailored to ASD patients. Pharmacological guidelines were iteratively refined until consensus was reached. Treatment differences relative to standard of care (SOC) of non-autistic individuals are noted. Key literature and clinical trial results were reviewed to supplement clinical experience.

Results: The pharmacological treatment pathways reflect how appropriate medication options for ASD patients can depend on many factors unique to the patient and can differ from established non-autistic SOC. Key takeaways include: For sleep disturbances in ASD, initial strategies align with non-autistic SOC, emphasizing sleep hygiene and melatonin use. First-line recommendations for treating ADHD, anxiety, and depression in ASD differ from non-autistic SOC; α₂-adrenergic agonists are more suitable than stimulants for some ASD-ADHD patients, buspirone and mirtazapine are preferred to selective serotonin reuptake inhibitors (SSRIs) for anxiety, and duloxetine, mirtazapine, bupropion, and vortioxetine are recommended ahead of SSRIs for depression. Addressing irritability in ASD requires interdisciplinary evaluation of contributing factors, and guanfacine, risperidone, or aripiprazole may be appropriate, depending on severity.

Conclusions: Recognition and treatment of co-occurring psychiatric and behavioral conditions in autistic patients must account for differences in clinical presentation and medication effectiveness and tolerability. Drawing on evidence-based clinical insights, these guidelines seek to support PCPs in making informed decisions when prescribing medications for ASD patients with co-occurring psychiatric and behavioral conditions, ultimately enhancing access to timely, comprehensive care for all individuals with ASD.