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Suicide is a major public health problem affecting US Veterans and the US in general. Many variables (e.g., demographic, clinical, biological, geographic) have been associated with risk for suicide and suicidal behavior, including altitude; however, the exact nature of the relationship between altitude and suicide remains unclear in part due to the fact that previous studies have used either geospatial data or individual-level data, but not both. Prior research has also failed to consider the full range of suicidal thoughts and behaviors, ranging from suicidal ideation to suicide deaths. Accordingly, the objective of the present research was to use both geospatial data (county and zip codes) and individual-level data to comprehensively assess the association between altitude and suicide mortality, suicide attempts, and suicidal ideation among US Veterans between 2000 and 2018. Taken together, our results demonstrate that there is a strong correlation between altitude and suicide rates at all the levels investigated and using different statistical analyses and even after controlling for significant covariates such as percent of age >50yr, percent male, percent white, percent non-Hispanic, median household income, and population density. We show that there is a positive correlation between altitude and suicide attempts especially when controlling by the covariates and a weak correlation between altitude and suicide ideation and the combination of suicide, suicide attempts and suicide ideation.

Background: The genetic association between urticaria and mental disorders and whether inflammatory cytokines mediate this process remains unclear. Materials and methods: A Mendelian randomization (MR) approaches to elucidate the causal relationship between urticaria and mental disorders and to validate the mediation of inflammatory cytokines. Genome‐wide association study (GWAS) databases used were obtained from Psychiatric Genomics Cooperation (PGC), GWAS Catalog, and FinnGen Consortium. Our study was conducted using inverse variance weighted (IVW) and Bayesian weighted MR (BWMR) methods for joint analysis. Results: The MR results showed that urticaria increased the risk of attention deficit hyperactivity disorder (ADHD) (odds ratio [OR] =$ = $ 1.088, 95% confidence interval [CI]: 1.026–1.154, p=$ = $ 0.0051); cholinergic urticaria increased the risk of bipolar disorder (BD) (OR =$ = $ 1.012, 95% CI: 1.001–1.022, p=$ = $ 0.0274); dermatographic urticaria increased the risk of ADHD (OR =$ = $ 1.057, 95% CI: 1.005–1.112, p=$ = $ 0.0323); idiopathic urticaria increased the risk of schizophrenia (SCZ) (OR =$ = $ 1.057, 95% CI: 1.005–1.112, p=$ = $ 0.0323); other unspecified urticaria increased the risk of ADHD (OR =$ = $ 1.085, 95% CI: 1.023–1.151, p=$ = $ 0.0063). We found that eight inflammatory cytokines were negatively associated with mental disorders and seven inflammatory cytokines were positively associated with mental disorders. Finally, our results suggested that inflammatory cytokines do not act as mediators between urticaria and mental disorders. Conclusions: Our study reveals a causal relationship between urticaria and the increased risk of mental disorders. We suggest that the treatment of urticaria could incorporate psychiatric interventions and mental health assessment of patients. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the effects of N‐carbamylglutamate (NCG) on piglets' growth performance and immune response, and to unravel the mechanisms of such effects. In a 2 × 2 factorial design including diet (with or without NCG) and immunological challenge (saline or lipopolysaccharide (LPS)), 24 piglets were randomly distributed into four groups. After being fed a basic diet or a NCG‐supplemented diet for 21 days, piglets were administered LPS or saline intraperitoneally. Results: The results showed that NCG increased the average daily gain and average daily feed intake, and the feed conversion ratio of piglets, and alleviated the adverse effects of LPS stimulation on intestinal morphology. At the phylum level, NCG reversed the increase in the abundance of Firmicutes and the reduction in that of Actinomycete caused by LPS stimulation. At the genus level, NCG increased the abundance of Lactobacillus, Blautia, norank_Butyricicoccaceae, Subdoligranulum, and Ruminococcus_gauvreauii_group, and LPS decreased the abundance of Escherichia‐Shigella and Ruminococcus_gauvreauii_group. The short‐chain fatty acid content was increased by NCG, but LPS reduced its content. N‐Carbamylglutamate also inhibited significantly the LPS‐induced increase in the relative expression of signal transducer and activator of transcription (STAT) 3, related orphan receptor (RAR) c, and pro‐inflammatory cytokines, and the decrease in the relative expression of STAT5, forkhead box P3, IL‐10 and transforming growth factor beta 1 mRNA. A significant correlation was found between intestinal microbiota and inflammatory cytokines and short‐chain fatty acids. Conclusion: N‐Carbamylglutamate can improve piglets' growth performance. It can also attenuate LPS‐induced intestinal inflammation by modulating microbiota and Th17/Treg balance‐related immune signaling pathways. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Background: The link between allergic diseases and dementia remains controversial, and the genetic causality of this link is unclear. Objective: This study investigated the causal relationship between allergic diseases and dementia using univariate and multivariate Mendelian randomization (MR) methods. Methods: We selected genome-wide association studies including 66,645 patients with allergic diseases and 12,281 patients with dementia, with statistical datasets derived from the FinnGen Consortium of European origin. After a rigorous screening process for single nucleotide polymorphisms to eliminate confounding effects, MR estimation was performed mainly using the inverse variance weighting method and the MR-Egger method. Sensitivity analyses were performed using Cochran's Q test, MR-PRESSO test, MR Pleiotropy residuals and leave-one-out analysis. Results: Univariate and multivariate MR together demonstrated a causal relationship between atopic dermatitis and reduced vascular dementia (VaD) risk (OR = 0.89, 95% CI: 0.81–0.99, p = 0.031; OR = 0.85, 95% CI: 0.76–0.95, p = 0.003). MVMR confirmed asthma was associated with a reduction in the risk of Alzheimer's disease (AD) (OR = 0.82, 95% CI: 0.71–0.94, p = 0.005) and may be associated with a reduction in the risk of VaD (OR = 0.80, 95% CI: 0.65–0.99, p = 0.042); allergic rhinitis may be causally associated with an increased risk of AD (OR = 1.16, 95% CI: 1.00–1.35, p = 0.046) and VaD (OR = 1.29, 95% CI: 1.03–1.62, p = 0.027). In sensitivity analyses, these findings were reliable. Conclusions: MR methods have only demonstrated that allergic rhinitis dementia is associated with an increased risk of developing dementia. Previously observed associations between other allergic diseases and dementia may be influenced by comorbidities and confounding factors rather than causality. [ABSTRACT FROM AUTHOR]

Epilepsy is the results from the imbalance between inhibition and excitation in neural circuits, which is mainly treated by some chemical drugs with side effects. Gain‐of‐function of BK channels or knockout of its β4 subunit associates with spontaneous epilepsy. Currently, few reports were published about the efficacy of BK(α + β4) channel modulators in epilepsy prevention. Charybdotoxin is a non‐specific inhibitor of BK and other K+ channels. Here, by nuclear magnetic resonance (NMR) and other biochemical techniques, we found that charybdotoxin might interact with the extracellular loop of human β4 subunit (i.e., hβ4‐loop) of BK(α + β4) channel at a molar ratio 4:1 (hβ4‐loop vs. charybdotoxin). Charybdotoxin enhanced its ability to prevent K+ current of BK(α + β4 H101Y) channel. The charybdotoxin Q18F variant selectively reduced the neuronal spiking frequency and increased interspike intervals of BK(α + β4) channel by π–π stacking interactions between its residue Phe18 and residue His101 of hβ4‐loop. Moreover, intrahippocampal infusion of charybdotoxin Q18F variant significantly increased latency time of seizure, reduced seizure duration and seizure numbers on pentylenetetrazole‐induced pre‐sensitized rats, inhibited hippocampal hyperexcitability and c‐Fos expression, and displayed neuroprotective effects on hippocampal neurons. These results implied that charybdotoxin Q18F variant could be potentially used for intractable epilepsy treatment by therapeutically targeting BK(α + β4) channel. [ABSTRACT FROM AUTHOR]

Introduction: We carried out a systematic review and meta-analysis to assess the safety and effectiveness of uterine artery embolization (UAE) compared with conventional hysterectomy on refractory postpartum hemorrhage (PPH).Methods: We searched PubMed, Embase, Chinese National Knowledge Infrastructure database (CNKI), Cochrane Library, and Wanfang database through October 2017 for randomized controlled trials (RCTs) and observational studies assessing the safety and effectiveness of UAE compared with hysterectomy on refractory PPH. The main outcome measures included the blood loss, operating time, hemostatic effective rate, and length of stay.Results: Six RCTs and nine observational studies were included in the meta-analysis, which involved 1142 women with refractory PPH. The results demonstrated that UAE was more beneficial on refractory PPH compared with hysterectomy using four scales: blood loss (WMD 893.39 mL; 95% CI: -1205.65, -581.13; p < .001); operating time (WMD -37.19 minutes; 95% CI: -44.42, -29.96; p < .001); length of stay (WMD -5.36 days; 95% CI: -5.76, -4.97; p < .001), hemostatic effective rate (OR 1.58, 95% CI: 0.80, 3.12, p = .184) .Conclusions: In the present meta-analysis, the positive findings suggest UAE has beneficial effects on refractory PPH. UAE significantly reduced blood loss, shortened the operating time, and length of stay compared with hysterectomy. And there is no difference between the UAE group and hysterectomy group in hemostatic effective rate. However, those findings should be treated with caution because of heterogeneity and potential biases. [ABSTRACT FROM AUTHOR]