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Key pointsr Dysregulation of nitric oxide (NO) signalling is associated with GI motility dysfunctions like chronic constipation, achalasia or Hirschsprung's disease. The inhibitory effect of NO is mainly exerted via NO-sensitive guanylyl cyclase (NO-GC) which is found in different gastrointestinal (GI) cell types including smooth muscle cells (SMCs) and interstitial cells of Cajal (ICC).r Here, we focus on the investigation of NO-GC function in murine colon. Using cell-specific knock-out mice, we demonstrate that NO-GC is expressed in myenteric ICC of murine colon and participates in regulation of colonic spontaneous contractions in longitudinal smooth muscle.r We report a novel finding that basal enteric NO release acts via myenteric ICC to influence the generation of spontaneous contractions whereas the effects of elevated endogenous NO are mediated by SMCS in the murine proximal colon.r These results help in understanding possible pathological mechanisms involved in slowed colonic action and colonic inertia. AbstractIn the enteric nervous systems, NO is released from nitrergic neurons as a major inhibitory neurotransmitter. NO acts via NO-sensitive guanylyl cyclase (NO-GC), which is found in different gastrointestinal (GI) cell types including smooth muscle cells (SMCs) and interstitial cells of Cajal (ICC). The precise mechanism of nitrergic signalling through these two cell types to regulate colonic spontaneous contractions is not fully understood yet. In the present study we investigated the impact of endogenous and exogenous NO on colonic contractile motor activity using mice lacking nitric oxide-sensitive guanylyl cyclase (NO-GC) globally and specifically in SMCs and ICC. Longitudinal smooth muscle of proximal colon from wild-type (WT) and knockout (KO) mouse strains exhibited spontaneous contractile activity ex vivo. WT and smooth muscle-specific guanylyl cyclase knockout (SMC-GCKO) colon showed an arrhythmic contractile activity with varying amplitudes and frequencies. In contrast, colon from global and ICC-specific guanylyl cyclase knockout (ICC-GCKO) animals showed a regular contractile rhythm with constant duration and amplitude of the rhythmic contractions. Nerve blockade (tetrodotoxin) or specific blockade of NO signalling (L-NAME, ODQ) did not significantly affect contractions of GCKO and ICC-GCKO colon whereas the arrhythmic contractile patterns of WT and SMC-GCKO colon were transformed into uniform motor patterns. In contrast, the response to electric field-stimulated neuronal NO release was similar in SMC-GCKO and global GCKO. In conclusion, our results indicate that basal enteric NO release acts via myenteric ICC to influence the generation of spontaneous contractions whereas the effects of elevated endogenous NO are mediated by SMCs in the murine proximal colon.B. Lies and K. Beck contributed equally to this work.

Background Due to the dramatic measures accompanying isolation and the general uncertainty and fear associated with COVID-19, patients and relatives may be at high risk for adverse psychological outcomes. Until now there has been limited research focusing on the prevalence of psychological distress and associated factors in COVID-19 patients and their relatives. The objective of our study was to assess psychological distress in COVID-19 patients and their relatives 30 days after hospital discharge. Methods In this prospective observational cohort study at two Swiss tertiary-care hospitals we included consecutive adult patients hospitalized between March and June 2020 for a proven COVID-19 and their relatives. Psychological distress was defined as symptoms of anxiety and/or depression measured with the Hospital Anxiety and Depression Scale (HADS), i.e., a score of ≥8 on the depression and/or anxiety subscale. We further evaluated symptoms of post-traumatic stress disorder (PTSD), defined as a score of ≥1.5 on the Impact of Event Scale-Revised (IES-R). Results Among 126 included patients, 24 (19.1%) had psychological distress and 10 (8.7%) had symptoms of PTSD 30 days after hospital discharge. In multivariate logistic regression analyses three factors were independently associated with psychological distress in patients: resilience (OR 0.82; 95%CI 0.71 to 0.94; p = 0.005), high levels of perceived stress (OR 1.21; 95%CI 1.06 to 1.38; p = 0.006) and low frequency of contact with relatives (OR 7.67; 95%CI 1.42 to 41.58; p = 0.018). The model showed good discrimination, with an area under the receiver-operating characteristic curve (AUC) of 0.92. Among 153 relatives, 35 (22.9%) showed symptoms of psychological distress, and 3 (2%) of PTSD. For relatives, resilience was negatively associated (OR 0.85; 95%CI 0.75 to 0.96; p = 0.007), whereas perceived overall burden caused by COVID-19 was positively associated with psychological distress (OR 1.72; 95%CI 1.31 to 2.25; p<0.001). The overall model also had good discrimination, with an AUC of 0.87. Conclusion A relevant number of COVID-19 patients as well as their relatives exhibited psychological distress 30 days after hospital discharge. These results might aid in development of strategies to prevent psychological distress in COVID-19 patients and their relatives.

IMPORTANCE Shortcomings in the education of patients at hospital discharge are associated with higher risks for treatment failure and hospital readmission. Whether improving communication at discharge through specific interventions has an association with patient-relevant outcomes remains unclear. OBJECTIVE To conduct a systematic review and meta-analysis on the association of communication interventions at hospital discharge with readmission rates and other patient-relevant outcomes.

Neurocognitive impulsivity impacts upon treatment completion and appears sensitive for the prediction of relapse and dropout in alcohol-dependent patients. Poorer GNG response inhibition and a tendency toward steeper discounting of delayed rewards should be regarded as neurocognitive risk factors, which can be identified early in the course of alcohol dependence treatment.

We conclude that short rings of murine colon can be effectively used to record spontaneous contractions. Although NO-GC in SMC determines smooth muscle tone, concerted action of NO-GC in both SMC and ICC modulates slow phasic contractions and large contractions.

Objective COVID-19 causes psychological distress for patients and their relatives at short term. However, little research addressed the longer-term psychological outcomes in this population. Therefore, we aimed to prospectively assess clinically relevant psychological distress in hospitalized patients with COVID-19 and their relatives 90 days after hospital discharge. Methods This exploratory, prospective, observational cohort study included consecutive adult patients hospitalized in two Swiss tertiary-care hospitals between March and June 2020 for confirmed COVID-19 and their relatives. The primary outcome was psychological distress defined as clinically relevant symptoms of anxiety and/or depression measured with the Hospital Anxiety and Depression Scale (HADS) 90 days after discharge. Results Clinically relevant psychological distress 90 days after hospital discharge was present in 23/108 patients (21.3%) and 22/120 relatives (18.3%). For patients, risk and protective factors associated with clinically relevant psychological distress included sociodemographic, illness-related, psychosocial, and hospital-related factors. A model including these factors showed good discrimination, with an area under the receiver-operating characteristic curve (AUC) of 0.84. For relatives, relevant risk factors were illness-related, psychosocial, and hospital-related factors. Resilience was negatively associated with anxiety and depression in both patients and relatives and regarding PTSD in relatives only. Conclusion COVID-19 is linked to clinically relevant psychological distress in a subgroup of patients and their relatives 90 days after hospitalization. If confirmed in an independent and larger patient cohort, knowledge about these potential risk and protective factors might help to develop preventive strategies.

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