Identification and investigation of depression-related molecular subtypes in inflammatory bowel disease and the anti-inflammatory mechanisms of paroxetine

BackgroundUp to 40 per cent of people with active inflammatory bowel disease (IBD) also suffer from mood disorders such as anxiety and depression. Notwithstanding, the fundamental biological pathways driving depression in IBD remain unknown.MethodsWe identified 33 core genes that drive depression in IBD patients and performed consensus molecular subtyping with the NMF algorithm in IBD. The CIBERSORT were employed to quantify the immune cells. Metabolic signature was characterized using the “IOBR” R package. The scoring system (D. score) based on PCA. Pre-clinical models are constructed using DSS.ResultsUsing transcriptome data from the GEO database of 630 IBD patients, we performed a thorough analysis of the correlation between IBD and depression in this research. Firstly, the samples were separated into two different molecular subtypes (D. cluster1 and D. cluster2) based on their biological signatures. Moreover, the immunological and metabolic differences between them were evaluated, and we discovered that D. cluster2 most closely resembled IBD patients concomitant with depression. We also developed a scoring system to assess the IBD-related depression and predict clinical response to anti-TNF- therapy, with a higher D. score suggesting more inflammation and worse reaction to biological therapies. Ultimately, we also identified through animal experiments an antidepressant, paroxetine, has the added benefit of lowering intestinal inflammation by controlling microorganisms in the digestive tract.ConclusionsThis study highlights that IBD patients with or without depression show significant variations and antidepressant paroxetine may help reduce intestinal inflammation

Toxicokinetics of short-chain chlorinated paraffins in Sprague-Dawley rats following single oral administration

Short-chain chlorinated paraffins (SCCPs) have attracted considerable attention for their characteristic of persistent organic pollutants. However, very limited information is available for their toxicokinetic characteristics, limiting the evaluation of their health risks. In this study, we performed a toxicokinetics study to explore the absorption and excretion processes of SCCPs (a mixture of C-10-, C-11-, C-12- and C-13- CPs) after a single oral administration to the Sprague Dawley rats. The toxicokinetic results showed that peak blood concentration of total SCCPs was attained at 2.8 day with C-max value of 2.3 mg L-1. The half-lives of total SCCPs in blood for the absorption t(1/2) (ka), distribution t(1/2) (alpha) and elimination phases t(1/2) (beta) were calculated to be 1.0,1.7 and 6.6 days, respectively. During the 28 days post-dosing, about 27.9% and 3.5% of orally administrated SCCPs were excreted through feces and urine without metabolism, respectively. Congener group abundance profiles indicate a relative increase of Cl-5-SCCPs in blood and urine in the elimination stage, and a higher accumulation of Cl8-10-SCCPs in feces. The distribution discrepancies of SCCPs congener groups in blood and excreta were more dependent on chlorine contents than on carbon chain lengths. (C) 2015 Elsevier Ltd. All rights reserved

Evaluation of Off-Hour Emergency Care in Acute Ischemic Stroke: Results from the China National Stroke Registry

<div><p>Background and Purpose</p><p>The quality of after-hour emergency care of patients with acute ischemic stroke is debatable. We therefore, sought to analyze the performance measures, quality of care and clinical outcomes in these patients admitted during off-hours.</p><p>Methods</p><p>Our study included 4493 patients from a selected cohort of patients admitted to the hospitals with ischemic stroke in the China National Stroke Registry (CNSR) from September 2007 to August 2008. On-hour presentation was defined as arrival at the emergency department from the scene between 8AM and 5PM from Monday through Friday. Off-hours included the remainder of the on-hours and statutory holidays. The association between off-hour presentation and outcome was analyzed using multivariate logistic-regression models.</p><p>Results</p><p>Off-hour presentation was identified in 2672 (59.5%) patients with ischemic stroke. Comparison of patients admitted during off-hours with those admitted during on-hours revealed an unadjusted odds ratio of in-hospital mortality of 1.38 (95% confidence interval, 1.04–1.85), which declined to 1.34 (95% confidence interval, 0.93–1.93) after adjusting for patient characteristics (especially, pre-hospital delay). No difference in 30-day mortality, total death or dependence at three, six and 12 months between two groups was observed. No association between off-hour admission and quality of care was found.</p><p>Conclusions</p><p>In the CNSR database, compared with on-hour patients, off-hour patients with acute ischemic stroke admitted to the emergency departments from scene manifested a higher incidence of in-hospital mortality. However, the difference in incidence and quality of care between the groups disappeared after adjusting for pre-hospital delay and other variables.</p></div

Unadjusted and Adjusted Odds Ratios of Poor Outcomes in Ischemic Stroke Patients: Off-hour versus On-hour Presentations.

<p>Abbreviations: OR, odds ratio; CI, confidence interval. Adjusted for age, sex, National Institutes of Health Stroke Scale, smoking, drinking, hypertension, coronary heart disease, atrial fibrillation, diabetes mellitus, dyslipidemia, IV rtPA, and time from onset to admission within three hours (pre-hospital delay).</p><p>Unadjusted and Adjusted Odds Ratios of Poor Outcomes in Ischemic Stroke Patients: Off-hour versus On-hour Presentations.</p

Patient flow diagram.

<p>Clinical characteristics of the analyzed population (n = 4493) were compared with patients without exact admission time and excluded from the analyzed patients (n = 1212). No differences in demographic characteristics or risk factor profiles were identified between the two groups, except for the NIHSS score and rtPA within three hours of stroke onset, as shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0138046#pone.0138046.s002" target="_blank">S2 Table</a>. Patients with exact admission time had higher NIHSS scores at admission and were more likely to receive rtPA compared with those without admission time.</p

Baseline Characteristics of Patients Admitted to the Emergency Departments between On-hour and Off-hour Presentations after Ischemic Stroke.

<p>Abbreviations: SD, standard deviation; BMI, body-mass index; IQR, interquartile range; TIA, transient ischemic attack; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; OCSP, Oxfordshire Community Stroke Project criteria; PACI, partial anterior circulation infarct; TACI, total anterior circulation infarct; LACI, lacunar infarct; POCI, posterior circulation infarct; IV rtPA, intravenous recombinant tissue plasminogen activator.</p><p>Baseline Characteristics of Patients Admitted to the Emergency Departments between On-hour and Off-hour Presentations after Ischemic Stroke.</p

Quality of Care Indicators and Off-hour vs On-hour Presentation after Ischemic Stroke.

<p>Abbreviations: DVT, deep vein thrombosis; AF, atrial fibrillation; (n/N, %): n, of adherence; N, of eligible; %, Adherence rate.</p><p>Quality of Care Indicators and Off-hour vs On-hour Presentation after Ischemic Stroke.</p