Explore the vast range of titles available.

Background Childhood adversity and trauma are prevalent risk factors for the development of mental health conditions. This two-part paper describes the conceptual basis and pilot implementation of a tiered model of pediatric population mental health, highlighting the local socioecological context in which it was developed and the trauma-informed approach used. Methods Using retrospective record review of three datasets from the primary and secondary care pediatric clinics of a large academic medical center, which were harmonized to cover the study period from July 1, 2023 to June 30, 2024, we conducted descriptive analyses of patients across three levels: pediatric primary care ( n  = 9535), an integrated primary care program, which embeds mental health clinicians in primary care ( n  = 267), and family-centered trauma-informed psychotherapies in secondary care ( n  = 63), designed to address emotion dysregulation in pre-adolescent children. Demographics and lifetime history of trauma and adversity (assessed with a comprehensive 19-item list coded based on standardized screeners) were assessed through electronic medical records. Results Relative to the pediatric primary care population, more patients in the integrated primary care program and trauma-informed psychotherapies identified as White. Using our 19-item assessment, the lifetime prevalence of adversity or trauma was nearly universal among patients in the integrated primary care (94.4%) and trauma-informed psychotherapy (98.4%) programs. However, the lifetime prevalence of childhood adversities differed significantly across the two programs (integrated primary care: 76.8%; trauma-informed psychotherapy: 98.4%) when we assessed prevalence based only on the 10-item Adverse Childhood Experiences Questionnaire (Felitti VJ, Anda RF, Nordenberg D, Williamson DF, Spitz AM, Edwards V, Koss MP, Marks JS, Am J Prev Med 14:245–58, 1998). There was a higher prevalence of family and parent-related adversities in the trauma-informed psychotherapy program. Conclusions Findings support the need for trauma-informed, population mental health approaches in pediatric care. Developmentally tailored, family-centered, transdiagnostic screening and interventions are essential. Study findings, including gaps in programmatic fiscal sustainability, suggest avenues for policy reform to support and scale trauma-informed programs like ours. Programs seeking to implement trauma-informed approaches should leverage implementation and participatory research to ensure effectiveness and equitable accessibility for patients of diverse identities.

Clonal hematopoiesis of indeterminate potential (CHIP) is associated with an increased risk of cardiovascular diseases (CVDs), putatively via inflammasome activation. We pursued an inflammatory gene modifier scan for CHIP-associated CVD risk among 424,651 UK Biobank participants. We identified CHIP using whole-exome sequencing data of blood DNA and modeled as a composite, considering all driver genes together, as well as separately for common drivers (DNMT3A, TET2, ASXL1, and JAK2). We developed predicted gene expression scores for 26 inflammasome-related genes and assessed how they modify CHIP-associated CVD risk. We identified IL1RAP as a potential key molecule for CHIP-associated CVD risk across genes and increased AIM2 gene expression leading to heightened JAK2- and ASXL1-associated CVD risk. We show that CRISPR-induced Asxl1-mutated murine macrophages had a particularly heightened inflammatory response to AIM2 agonism, associated with an increased DNA damage response, as well as increased IL-10 secretion, mirroring a CVD-protective effect of IL10 expression in ASXL1 CHIP. Our study supports the role of inflammasomes in CHIP-associated CVD and provides evidence to support gene-specific strategies to address CHIP-associated CVD risk.

Mitochondria carry their own circular genome and disruption of the mitochondrial genome is associated with various aging-related diseases. Unlike the nuclear genome, mitochondrial DNA (mtDNA) can be present at 1000 s to 10,000 s copies in somatic cells and variants may exist in a state of heteroplasmy, where only a fraction of the DNA molecules harbors a particular variant. We quantify mtDNA heteroplasmy in 194,871 participants in the UK Biobank and find that heteroplasmy is associated with a 1.5-fold increased risk of all-cause mortality. Additionally, we functionally characterize mtDNA single nucleotide variants (SNVs) using a constraint-based score, mitochondrial local constraint score sum (MSS) and find it associated with all-cause mortality, and with the prevalence and incidence of cancer and cancer-related mortality, particularly leukemia. These results indicate that mitochondria may have a functional role in certain cancers, and mitochondrial heteroplasmic SNVs may serve as a prognostic marker for cancer, especially for leukemia. Mitochondrial DNA is known to exhibit heterogeneity of variants, even within a single cell. Here, the authors assessed this heteroplasmy of mitochondrial DNA within the UK Biobank cohort and showed that the presence of heteroplasmy and a functional score generated from heteroplasmic SNVs were associated with all-cause mortality and certain cancers.

Background Phytoplasmas are bacteria without cell walls from the class Mollicutes . They are obligate intracellular plant pathogens which cause diseases in hundreds of economically important plants including the grapevine ( Vitis vinifera ). Knowledge of their biology and the mechanisms of their interactions with hosts is largely unknown because they are uncultivable and experimentally inaccessible in their hosts. We detail here the global transcriptional profiling in grapevine responses to phytoplasmas. The gene expression patterns were followed in leaf midribs of grapevine cv. 'Chardonnay' naturally infected with a phytoplasma from the stolbur group 16SrXII-A, which is associated with the grapevine yellows disease 'Bois noir'. Results We established an on field experimental system in a productive vineyard that allowed application of molecular tools in a plant natural environment. Global transcription profiles of infected samples were compared with the healthy ones using microarray datasets and metabolic pathway analysis software (MapMan). The two-year-long experiment revealed that plant genes involved in primary and secondary metabolic pathways were changed in response to infection and that these changes might support phytoplasma nutrition. A hypothesis that phytoplasmas interact with the plant carbohydrate metabolism was proven and some possibilities how the products of this pathway might be utilized by phytoplasmas are discussed. In addition, several photosynthetic genes were largely down-regulated in infected plants, whereas defense genes from the metabolic pathway leading to formation of flavonoids and some PR proteins were significantly induced. Few other genes involved in defense-signaling were differentially expressed in healthy and infected plants. A set of 17 selected genes from several differentially expressed pathways was additionally analyzed with quantitative real-time PCR and confirmed to be suitable for a reliable classification of infected plants and for the characterization of susceptibility features in the field conditions. Conclusion This study revealed some fundamental aspects of grapevine interactions with the stolbur 'Bois noir' phytoplasma in particular and some plant interactions with phytoplasmas in general. In addition, the results of the study will likely have an impact on grape improvement by yielding marker genes that can be used in new diagnostic assays for phytoplasmas or by identifying candidate genes that contribute to the improved properties of grape.

We performed genome-wide meta-analysis of lipid traits on three samples of Mexican and Mexican American ancestry comprising 4,383 individuals and followed up significant and highly suggestive associations in three additional Hispanic samples comprising 7,876 individuals. Genome-wide significant signals were observed in or near CELSR2 , ZNF259/APOA5 , KANK2/DOCK6 and NCAN/MAU2 for total cholesterol, LPL, ABCA1, ZNF259/APOA5 , LIPC and CETP for HDL cholesterol, CELSR2, APOB and NCAN/MAU2 for LDL cholesterol and GCKR , TRIB1 , ZNF259/APOA5 and NCAN/ MAU2 for triglycerides. Linkage disequilibrium and conditional analyses indicate that signals observed at ABCA1 and LIPC for HDL cholesterol and NCAN/MAU2 for triglycerides are independent of previously reported lead SNP associations. Analyses of lead SNPs from the European Global Lipids Genetics Consortium (GLGC) dataset in our Hispanic samples show remarkable concordance of direction of effects as well as strong correlation in effect sizes. A meta-analysis of the European GLGC and our Hispanic datasets identified five novel regions reaching genome-wide significance: two for total cholesterol ( FN1 and SAMM50 ), two for HDL cholesterol ( LOC100996634 and COPB1 ) and one for LDL cholesterol ( LINC00324/CTC1/PFAS ). The top meta-analysis signals were found to be enriched for SNPs associated with gene expression in a tissue-specific fashion, suggesting an enrichment of tissue-specific function in lipid-associated loci.

Pericardial fat is a localized fat depot associated with coronary artery calcium and myocardial infarction. We hypothesized that genetic loci would be associated with pericardial fat independent of other body fat depots. Pericardial fat was quantified in 5,487 individuals of European ancestry from the Framingham Heart Study (FHS) and the Multi-Ethnic Study of Atherosclerosis (MESA). Genotyping was performed using standard arrays and imputed to ~2.5 million Hapmap SNPs. Each study performed a genome-wide association analysis of pericardial fat adjusted for age, sex, weight, and height. A weighted z-score meta-analysis was conducted, and validation was obtained in an additional 3,602 multi-ethnic individuals from the MESA study. We identified a genome-wide significant signal in our primary meta-analysis at rs10198628 near TRIB2 (MAF 0.49, p = 2.7 × 10(-08)). This SNP was not associated with visceral fat (p = 0.17) or body mass index (p = 0.38), although we observed direction-consistent, nominal significance with visceral fat adjusted for BMI (p = 0.01) in the Framingham Heart Study. Our findings were robust among African ancestry (n = 1,442, p = 0.001), Hispanic (n = 1,399, p = 0.004), and Chinese (n = 761, p = 0.007) participants from the MESA study, with a combined p-value of 5.4E-14. We observed TRIB2 gene expression in the pericardial fat of mice. rs10198628 near TRIB2 is associated with pericardial fat but not measures of generalized or visceral adiposity, reinforcing the concept that there are unique genetic underpinnings to ectopic fat distribution.

Back pain is the #1 cause of years lived with disability worldwide, yet surprisingly little is known regarding the biology underlying this symptom. We conducted a genome-wide association study (GWAS) meta-analysis of chronic back pain (CBP). Adults of European ancestry were included from 15 cohorts in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and from the UK Biobank interim data release. CBP cases were defined as those reporting back pain present for ≥3-6 months; non-cases were included as comparisons (\"controls\"). Each cohort conducted genotyping using commercially available arrays followed by imputation. GWAS used logistic regression models with additive genetic effects, adjusting for age, sex, study-specific covariates, and population substructure. The threshold for genome-wide significance in the fixed-effect inverse-variance weighted meta-analysis was p<5×10(-8). Suggestive (p<5×10(-7)) and genome-wide significant (p<5×10(-8)) variants were carried forward for replication or further investigation in the remaining UK Biobank participants not included in the discovery sample. The discovery sample comprised 158,025 individuals, including 29,531 CBP cases. A genome-wide significant association was found for the intronic variant rs12310519 in SOX5 (OR 1.08, p = 7.2×10(-10)). This was subsequently replicated in 283,752 UK Biobank participants not included in the discovery sample, including 50,915 cases (OR 1.06, p = 5.3×10(-11)), and exceeded genome-wide significance in joint meta-analysis (OR 1.07, p = 4.5×10(-19)). We found suggestive associations at three other loci in the discovery sample, two of which exceeded genome-wide significance in joint meta-analysis: an intergenic variant, rs7833174, located between CCDC26 and GSDMC (OR 1.05, p = 4.4×10(-13)), and an intronic variant, rs4384683, in DCC (OR 0.97, p = 2.4×10(-10)). In this first reported meta-analysis of GWAS for CBP, we identified and replicated a genetic locus associated with CBP (SOX5). We also identified 2 other loci that reached genome-wide significance in a 2-stage joint meta-analysis (CCDC26/GSDMC and DCC).

OBJECTIVE: Many studies have documented associations between inflammation and type 2 diabetes incidence. We assessed potential variability in this association in the major U.S. racial/ethnic groups. RESEARCH DESIGN AND METHODS: Incident type 2 diabetes was assessed among men and women aged 45-84 years without prior clinical cardiovascular disease or diabetes in the prospective Multi-Ethnic Study of Atherosclerosis. Interleukin (IL)-6, fibrinogen, and C-reactive protein (CRP) were measured at baseline (2000-2002); fasting glucose and diabetes medication use was assessed at baseline and three subsequent in-person exams through 2007. Type 2 diabetes was defined as use of diabetes drugs or glucose ≥126 mg/dl. Covariates included baseline demographics, clinic, smoking, alcohol, exercise, hypertension medication, systolic blood pressure, insulin resistance, and BMI. Cox proportional hazards regression was used to calculate hazard ratios (HRs) by quartiles of CRP, IL-6, and fibrinogen. RESULTS: Among 5,571 participants (mean age 61.6 years, 53% female, 42.1% white, 11.5% Chinese, 25.7% black, and 20.7% Hispanic), 410 developed incident diabetes during a median follow-up time of 4.7 years (incidence 16.8 per 1,000 person-years). CRP, IL-6, and fibrinogen levels were associated with incident diabetes in the entire sample. After adjustment, the associations were attenuated; however, quartile 4 (versus quartile 1) of IL-6 (HR 1.5 [95% CI 1.1-2.2]) and CRP (1.7 [1.3-2.4]) remained associated with incident diabetes. In stratified analyses, similar associations were observed among white, black, and Hispanic participants. CONCLUSIONS: Higher levels of inflammation predict short-term incidence of type 2 diabetes in a multiethnic American sample.

Asynchronous Learning Networks (ALN) are a form of \"e-learning\" that emphasizes the use of the Internet to support class discussions and activities. This paper presents a qualitative study of role changes that occur when faculty become online or \"virtual\" professors. In 20 semi-structured interviews of faculty, coded with pattern analysis software, the authors captured role changes enacted by instructors in ALN settings - cognitive roles, affective roles, and managerial roles. The cognitive role, which relates to mental processes of learning, information storage, and thinking, shifts to one of deeper cognitive complexity. The affective role, which relates to influencing the relationships between students, the instructor, and the classroom atmosphere, required faculty to find new tools to express emotion, yet they found the relationship with students more intimate. The managerial role, which deals with class and course management, requires greater attention to detail, more structure, and additional student monitoring. Overall, faculty reported a change in their teaching persona, toward more precision in their presentation of materials and instructions, combined with a shift to a more Socratic pedagogy, emphasizing multilogues with students. The main sources of frustration and of fulfillment of the virtual professor are explored.