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Background: Psychological factors contribute to the pathogenesis of functional dyspepsia (FD). Antidepressant agents are beneficial in treatment of refractory FD. However, their efficacy is greatly hindered by the poor treatment adherence. Stigma is present in patients with chronic diseases or mental disorders and could affect adherence. The present study was aimed to evaluate stigma prevalence in FD patients and to explore the impact of stigma on treatment adherence to antidepressants. Methods: Functional dyspepsia patients unsatisfied with the regular first‐line treatment and received newly initiated antidepressant medicine were recruited and subjected to antidepressant treatment for 8 weeks. Stigma scales and symptom scores of dyspepsia, depression, and anxiety were analyzed before and after treatment. Associations between stigma and medication adherence were evaluated. Key results: One hundred and ten of the enrolled 138 participants reported minimal disease‐related internalized stigma, and 28 reported mild stigma before antidepressant therapy. Male gender, lower education, and higher scores of dyspepsia, depression, and anxiety were predictors of stigma before treatment. The mean stigma scores increased after 8‐week antidepressant treatment. A proportion (36.4%‐89.9%) of patients showed stigma attached to antidepressant therapy in the 4‐question survey. Post‐treatment stigma scores negatively correlated with treatment adherence and efficacy. Patients with decreased post‐treatment stigma scores displayed better medication adherence and symptom improvement compared to those with elevated or unaltered post‐treatment stigma scores. Conclusions: Patients with refractory FD report stigma attached to the disease and antidepressants. It is an obstacle to treatment adherence and efficacy of antidepressant medication in FD therapy. [ABSTRACT FROM AUTHOR]

Serotonin (5-HT) plays pivotal roles in the pathogenesis of postinfectious irritable bowel syndrome (PI-IBS), and luminal 5-HT time-dependently modulates visceral nociception. We found that duodenal biopsies from PI-IBS patients exhibited increased 5-HT and decreased anandamide levels and that decreased anandamide was associated with abdominal pain severity, indicating a link between 5-HT and endocannabinoid signaling pathways in PI-IBS. To understand this, we investigated the role of endocannabinoids in 5-HT modulation of visceral nociception in a rat model. Acute intraduodenally applied 5-HT attenuated the visceromotor response (VMR) to colorectal distention, and this was reversed by the cannabinoid receptor 1 (CB 1 ) antagonist AM251. Duodenal anandamide (but not 2-arachidonoylglycerol) content was greatly increased after luminal 5-HT treatment. This effect was abrogated by the 5-HT 3 receptor (5-HT 3 R) antagonist granisetron, which was luminally delivered to preferentially target vagal terminals. Chemical denervation of vagal afferents blocked 5-HT-evoked antinociception and anandamide release. Chronic luminal 5-HT exposure for 5 days increased baseline VMR and VMR post-5-HT (days 4 and 5). Duodenal levels of anandamide and N-acyl-phosphatidylethanolamine-specific phospholipase D (NAPE-PLD, the anandamide-synthesizing enzyme) protein gradually declined from day 1 to 5. The time-dependent effects of 5-HT were abolished by daily granisetron pretreatment. Daily pretreatment with CB 1 agonists or anandamide from day 3 attenuated 5-HT-induced hyperalgesia. These data suggest that vagal 5-HT 3 R-mediated duodenal anandamide release contributes to acute luminal 5-HT-induced antinociception via CB 1 signaling, whereas decreased anandamide is associated with hyperalgesia upon chronic 5-HT treatment. Further understanding of peripheral vagal anandamide signaling may provide insights into the mechanisms underlying 5-HT-related IBS. [ABSTRACT FROM AUTHOR]

purpose of this study was to analyze the improvement effect of clinical pharmacist intervention on renal function impairment in patients with antimicrobial-induced acute kidney injury (AKI). Methods: A total of 145 patients with AKI caused by antibiotics admitted to the ICU department were selected as the research subjects. The patients were divided into the control group (n=57) and the intervention group (n=88) according to whether there were ICU specialist clinical pharmacists involved in clinical treatment. The renal function outcome and infection control were evaluated in the two groups. Results: The proportion of renal function outcome in the intervention group was 88.6%, which was significantly higher than that in the control group. However, there was no statistically significant difference in infection control between the two groups. For the intervention group, the clinical pharmacists adopted three intervention methods: dose adjustment, drug replacement and CRRT treatment, respectively, according to the disease conditions of AKI patients. Among them, dose adjustment and drug replacement were the most frequently used intervention methods. In addition, the proportion of renal function outcome was higher in the group of patients who changed antibiotics and underwent CRRT, which were 93.1% and 100%, respectively. The adjusted-dose group had the highest infection control rate at 82.1%. However, there were no statistically significant differences in renal function outcomes and infection control among the three interventions. Conclusion: Clinical pharmacists participating in the clinical treatment of patients with antimicrobial-induced AKI in ICU can effectively improve the renal function of patients. [ABSTRACT FROM AUTHOR]

Mucosal bile acid (BA) profile is still unestablished in diarrhea-predominant irritable bowel syndrome (IBS-D). The aim of this study was to explore colonic mucosal BAs and their associations with mucosal mast cell (MMC)-derived nerve growth factor (NGF) and bowel symptoms in IBS-D. Colonic mucosal biopsies from 36 IBS-D patients and 35 healthy controls (HCs) were obtained for targeted BA profiling. MMC count and the expression of NGF and tight junction proteins (TJPs) were examined. We found that colonic mucosal BA profile was altered in the IBS-D cohort. The proportion of primary BAs was significantly higher and that of secondary BAs was lower in IBS-D patients. According to the 90th percentile of total mucosal BA content of HCs, IBS-D patients were divided into BA-H (n = 7, 19.4%) and BA-L (n = 29, 80.6%) subgroups. BA-H patients showed significantly higher total mucosal BA content compared to BA-L subgroup and HCs. The mucosal content of 11 BA metabolites significantly increased in BA-H subgroup, e.g. cholic acid (CA) and taurocholic acid (TCA). Moreover, BA-H patients displayed significantly elevated MMC count and NGF expression, with decreased expression of TJPs (claudin-1, junctional adhesion molecule-A and zonula occludens-1). Correlation analyses revealed that mucosal TCA content positively correlated with MMC count, MMC-derived NGF levels, and abdominal pain while negatively correlated with TJP expression. In conclusion, IBS-D patients showed an altered BA profile in the colonic mucosa. Approximately 20% of them exhibit elevated mucosal BA content, which may be associated with MMC-derived NGF signaling and bowel symptoms. Graphical Abstract [ABSTRACT FROM AUTHOR]

Objective To analyze autonomic functioning which presented as the high frequency ( HF) component of heart rate variability, a measurement of vagal tone, and the ratio of low frequency ( LF) to HF (LF : HF), an indicator of sympathovagal balance in irritable bowel syndrome ( IBS) patients. Methods We identified relevant studies by performing a literature search of MEDLINE, EMBASE and the ISI Web of Knowledge to 31 March 2013. Pooled effect sizes with 95% confidence interval ( CI) were calculated using a random effects model. Between-study heterogeneity was assessed using the Q test and I2 statistic. Results In all, 11 articles including 392 IBS patients and 263 controls met the inclusion criteria of the analysis. IBS patients had lower HF band power ( Hedges's g = −0.38, 95% CI −0.68 to −0.09) than the controls ( I2 = 63.6%, P = 0.003). Moreover, IBS patients showed a higher LF : HF ( Hedges's g = 0.43, 95% CI 0.13-0.74), with no significant heterogeneity. A subgroup analysis of the HF index according to the recording time yielded different results for the IBS patients and controls. Additionally, constipation-predominant IBS ( IBS- C) patients had decreased HF band power, whereas no significant difference was found in LF : HF. Conclusions Impaired parasympathetic functioning and abnormal sympathovagal balance may be involved in the pathogenesis of IBS. Vagal dysfunction is more obvious in the IBS- C subgroup. [ABSTRACT FROM AUTHOR]

Background: Ischemic stroke (IS) is a common cause of death from vascular diseases. Studies have found that smoking increases the risk of ischemic stroke, but the association of smoking with the outcome of IS remains unclear. This meta-analysis aims to investigate the effect of smoking on the prognosis of IS. Methods: We searched four electronic databases including PubMed, EMBASE, Cochrane library and Web of science for papers, published before January 2019. In this meta-analysis, Review Manager 5.3 software was used to calculate for the pooled estimate effect, as well as the inverse-variance method for pooled mean difference (MD) and odds ratio (OR) of incidence in two groups of population. Results: A total of 14,789 citations were identified during the literature search, 21 studies were included in the meta-analyses after screening. The full-adjusted OR of poor prognostic outcome in smoking and nonsmoking patients with stroke was pooled as 0.96 (95% CI 0.77–1.21), suggested that smoking or not has no impact on prognosis of IS. The pooled MD of onset age between smoking and nonsmoking IS patients was − 10.05 (− 12.91, − 7.19), indicated that smoking causes first onset of IS to occur 10 years earlier. Conclusions: This meta-analysis showed that smoking was not a protective factor for poor prognosis of IS. Smoking patients with IS are 10 years younger than nonsmoking patients at time of the first onset of stroke. [ABSTRACT FROM AUTHOR]

Background: Psychological stress is an important factor for the development and recurrence of irritable bowel syndrome (IBS). The mechanisms underlying stress‐induced visceral hypersensitivity (VH), a key pathophysiological component in IBS, are still incompletely understood. We aimed to test whether transient receptor potential melastatin 8 (TRPM8) participates in acute stress–induced VH. Methods: Rats were subjected to 1‐hour water avoidance stress (WAS). Visceral sensitivity was measured with visceromotor response to colorectal distension. Western blot and immunofluorescence were applied to evaluate the expression of GR and TRPM8 and activation of PKA, Akt, and PKC pathways. Results: WAS‐caused VH depended on glucocorticoid receptors (GRs) and TRPM8 channels. In a dorsal root ganglion (DRG)–derived cell line, corticosterone rapidly (within 30 minutes) induced membrane expression of TRPM8. This effect was inhibited by GR antagonism and was mimicked by membrane‐impermeable corticosterone. PKA, PI3K/Akt, and PKC pathways, which lied downstream of GR and acted in parallel to promote membrane expression of TRPM8, contributed to WAS‐induced VH. The non‐receptor tyrosine kinase Pyk2, which may serve as a convergence point for PKA, PI3K/Akt, and PKC pathways, facilitated membrane insertion of TRPM8 via tyrosine‐phosphorylating TRPM8 in L6‐S2 DRGs and participated in WAS‐induced VH. Conclusions: Collectively, acute stress–induced VH could involve membrane‐bound GR‐dependent enhancement of TRPM8 function in nociceptive DRG neurons. Mechanistically, Pyk2 could act as a key mediator that coordinates multiple protein kinase signaling and triggers phosphorylation and membrane insertion of TRPM8. [ABSTRACT FROM AUTHOR]

Objective Chordoid meningioma (CM) and clear-cell meningioma (CCM) are rare World Health Organization grade II meningioma subtypes. This study aimed to evaluate favorable factors and appropriate therapeutic strategies for these lesions. Methods We retrospectively reviewed clinical data from 111 cases of grade II meningiomas, including 55 cases of CM and 56 cases of CCM, between January 2011 and December 2015. Results The mean follow-up time of the rare World Health Organization grade II meningiomas ( n = 111) was 45.3 months. In the CM group, 8 patients (14.5%) experienced recurrence, and 2 patients (3.6%) died. In the CCM group, 22 patients (39.3%) experienced recurrence, and 9 patients (16.1%) died. Significant differences were observed between the CM and CCM groups in tumor size ( P = 0.019), history of surgery ( P = 0.038), and peritumoral edema ( P = 0.004). In the CM group, gross total resection was associated with favorable progression-free survival (hazard ratio, 0.144; 95% confidence interval, 0.029–0.714; P = 0.018). In the CCM group, univariate analyses showed that preoperative Karnofsky Performance Status <80 ( P < 0.001), tumor size ≥5 cm ( P = 0.015), tumor size (per-centimeter increase) ( P = 0.022), bone invasion ( P = 0.004), a history of surgery ( P < 0.001), and subtotal resection ( P = 0.009) were associated with worse progression-free survival. Male gender ( P = 0.039), tumor size (per-centimeter increase) ( P = 0.043), bone invasion ( P = 0.030), and a history of surgery ( P = 0.007) were associated with poor overall survival. Conclusions This study showed that gross total resection should be achieved in grade II meningiomas. Patients with larger tumors and/or surgical histories had worse outcomes. [ABSTRACT FROM AUTHOR]