Psychiatric disorders are the leading cause of disability worldwide while the pathogenesis remains unclear. Genome-wide association studies (GWASs) have made great achievements in detecting disease-related genetic variants. However, functional information on the underlying biological processes is often lacking. Current reports propose the use of metabolic traits as functional intermediate phenotypes (the so-called genetically determined metabotypes or GDMs) to reveal the biological mechanisms of genetics in human diseases. Here we conducted a two-sample Mendelian randomization analysis that uses GDMs to assess the causal effects of 486 human serum metabolites on 5 major psychiatric disorders, which respectively were schizophrenia (SCZ), major depression (MDD), bipolar disorder (BIP), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD). Using genetic variants as proxies, our study has identified 137 metabolites linked to the risk of psychiatric disorders, including 2-methoxyacetaminophen sulfate, which affects SCZ (P = 1.7 × 10–5) and 1-docosahexaenoylglycerophosphocholine, which affects ADHD (P = 5.6 × 10–5). Fourteen significant metabolic pathways involved in the 5 psychiatric disorders assessed were also detected, such as glycine, serine, and threonine metabolism for SCZ (P = .0238), Aminoacyl-tRNA biosynthesis for both MDD (P = .0144) and ADHD (P = .0029). Our study provided novel insights into integrating metabolomics with genomics in order to understand the mechanisms underlying the pathogenesis of human diseases.
21 March 2023 in Journal of the American Heart Association
Background: Previous studies found an association between self‐reported sleep duration and mortality. This study aimed to compare the effects of objective and self‐reported sleep duration on all‐cause and cardiovascular disease (CVD) mortality. Methods and Results: A total of 2341 men and 2686 women (aged 63.9±11.1 years) were selected from the SHHS (Sleep Heart Health Study). Objective sleep duration was acquired using in‐home polysomnography records, and self‐reported sleep duration on weekdays and weekends was based on a sleep habits questionnaire. The sleep duration was categorized as ≤4 hours, 4 to 5 hours, 5 to 6 hours, 6 to 7 hours, 7 to 8 hours, and >8 hours. Multivariable Cox regression analysis was used to investigate the association of objective and self‐reported sleep duration with all‐cause and CVD mortality. During a mean follow‐up period of 11 years, 1172 (23.3%) participants died, including 359 (7.1%) deaths from CVD. All‐cause and CVD mortality rates decreased gradually with increasing objective sleep duration. In multivariable Cox regression analysis, the greatest association for all‐cause and CVD mortality was with an objective sleep duration of 5 hours or shorter. In addition, we found a J‐shaped association of self‐reported sleep duration on both weekdays and weekends with all‐cause and CVD mortality. Self‐reported short (≤4 hours) and long (>8 hours) sleep duration on weekdays and weekends were associated with an increased risk of all‐cause and CVD mortality compared with 7 to 8 hours sleep duration. Furthermore, a weak correlation was observed between objective and self‐reported sleep duration. Conclusions: This study showed that both objective and self‐reported sleep duration were associated with all‐cause and CVD mortality, but with different characteristics. Registration: URL: https://clinicaltrials.gov/ct2/show/NCT00005275 ; Unique identifier: NCT00005275.
Background: Virtual simulation and face-to-face simulation are effective for clinical judgment training. Rare studies have tried to improve clinical judgment ability by applying virtual simulation and face-to-face simulation together. This study aimed to evaluate the effect of an integrated non-immersive virtual simulation and high-fidelity face-to-face simulation program on enhancing nursing students’ clinical judgment ability and understanding of nursing students’ experiences of the combined simulation. Methods: A sequential exploratory mixed-methods study was conducted in a nursing simulation center of a university in Central China. Third-year nursing students (n = 122) taking clinical training in ICUs were subsequentially assigned to the integrated non-immersive virtual simulation and high-fidelity face-to-face simulation program arm (n = 61) or the face-to-face simulation-only arm (n = 61) according to the order in which they entered in ICU training. Clinical judgment ability was measured by the Lasater Clinical Judgment Rubric (LCJR). Focus group interviews were conducted to gather qualitative data. Results: Students in both arms demonstrated significant improvement in clinical judgment ability scores after simulation, and students in the integrated arm reported more improvement than students in the face-to-face simulation-only arm. The qualitative quotes provided a context for the quantitative improvement measured by the LJCR in the integrated arm. Most of the quantitative findings were confirmed by qualitative findings, including the domains and items in the LJCR. The findings verified and favored the effect of the combination of non-immersive virtual simulation and high-fidelity face-to-face simulation integrated program on enhancing nursing students’ clinical judgment ability. Conclusions: The integrated virtual simulation and face-to-face simulation program was feasible and enhanced nursing students’ self-reported clinical judgment ability. This integrated non-immersive virtual simulation and high-fidelity face-to-face simulation program may benefit nursing students and newly graduated nurses in the ICU more than face-to-face simulation only.
Macrocytic anemia is common in liver disease. However, its role in hepatitis B virus (HBV)-related decompensated cirrhosis remains unknown. The aim of the present study was to determine the association between macrocytic anemia and the severity of liver impairment in patients with HBV-related decompensated cirrhosis according to the Model for End Stage Liver Disease (MELD) score. A total of 463 participants who fulfilled our criteria were enrolled in this cross-sectional study. Patients were classified into three groups according to anemia types, diagnosed based on their mean corpuscular volume level. Multivariate linear regression analyses were used to determine the association between macrocytic anemia and the MELD score for patients with HBV-related decompensated cirrhosis. Patients with macrocytic anemia had evidently higher MELD scores (10.8 ± 6.6) than those with normocytic anemia (8.0 ± 5.5) or microcytic anemia (6.3 ± 5.1). The association remained robust after adjusting for age, gender, smoking, drinking, and total cholesterol (β = 1.94, CI: 0.81–3.07, P < 0.001). Macrocytic anemia was found to be associated with the severity of liver impairment and might be a predictor for short-term mortality in patients with HBV-related decompensated cirrhosis.
1 December 2018 in Neuroscience & Biobehavioral Reviews
Attention deficit hyperactivity disorder (ADHD), bipolar disorder (BP) and schizophrenia (SCZ) are complex psychiatric disorders. We conducted a large-scale integrative analysis of genome-wide association studies (GWAS) and life course consistent methylation quantitative trait loci (meQTLs) datasets. The GWAS data of ADHD (including 20,183 cases and 35,191 controls), BP (including 7481 cases and 9250 controls) and SCZ (including 36,989 cases and 113,075 controls) were derived from published GWAS. Life course consistent meQTLs dataset was obtained from a longitudinal meQTLs analysis of 1018 mother-child pairs. Gene prioritization, pathway and tissue/cell type enrichment analysis were conducted by DEPICT. We identified multiple genes and pathways with common or disease specific effects, such as NISCH (P = 9.87 x 10(-3) for BP and 2.49 x 10(-6) for SCZ), ST3GAL3 (P = 1.19 x 10(-2) for ADHD), and KEGG_MAPK_SIGNALING_PATHWAY (P = 1.56 x 10(-3) for ADHD, P = 4.71 x 10(-3) for BP, P = 4.60 x 10(-4) for SCZ). Our study provides novel clues for understanding the genetic mechanism of ADHD, BP and SCZ.
Following a ban on antibiotic use in the feed industry, trials on the effects of various immunostimulants (prebiotics, probiotics, antimicrobial peptides [AMPs], and herbs) on the survival, growth, immunity, and disease control of farmed fish in aquaculture are being rapidly conducted. The wide variety of microbes with roles in nutrition, metabolism, and immunity in the fish intestine is the primary factor affecting the fermentability and functionality of dietary immunostimulants. For this reason, the dynamic interactions between immunostimulants and the intestinal microbiome may influence fish health. In this study, the effects of two agriculturally important AMPs (nisin and cecropin) and one herb (Penthorum chinense) on the gut microbiome of common carp were investigated, using 16S rDNA high-throughput sequencing. The results suggest that all three substances can alter the richness, diversity, and composition of the intestinal microbiota of common carp. P. chinense had a similar effect on the gut microbiota of common carp to that of nisin, and both promoted more striking changes in the gut microbiota community than did cecropin. The relative abundance of Proteobacteria was lower in the nisin and P. chinense groups than in the control and cecropin groups. The relative abundance of Bacteroidetes in the nisin, cecropin, and P. chinense groups was markedly increased, compared with that of the control group. Additionally, nisin, cecropin, and P. chinense showed obvious anti-inflammatory effects on the fish intestine, which was reflected by significantly increasing the expression levels of two anti-inflammatory cytokines IL-10 and TGF-β. Some digestive enzyme activities in the fish intestine were also significantly enhanced by supplementing these three substances in feeds.