Subcutaneous nerve activity and mechanisms of sudden death in a rat model of chronic kidney disease

BACKGROUND: The mechanisms of sudden death in chronic kidney disease (CKD) remain unclear. OBJECTIVE: The purpose of this study was to test the hypotheses that subcutaneous nerve activity (SCNA) can be used to estimate sympathetic tone in ambulatory rats and that abrupt reduction of SCNA precedes the spontaneous arrhythmic death of Cy/+ rats. METHODS: Radiotransmitters were implanted in ambulatory normal (N = 6) and Cy/+ (CKD; N = 6) rats to record electrocardiogram and SCNA. Two additional rats were studied before and after chemical sympathectomy with 6-hydroxydopamine. RESULTS: In normal rats, the baseline heart rate (HR) and SCNA were 351 ± 29 bpm and 5.12 ± 2.97 mV·s, respectively. SCNA abruptly increased HR by 4.31% (95% confidence interval 4.15%-4.47%). In comparison, the CKD rats had reduced baseline HR (336 ± 21 bpm, P < .01) and SCNA (4.27 ± 3.19 mV·s, P < .01). When SCNA was observed, HR increased by only 2.48% (confidence interval 2.29%-2.67%, P < .01). All Cy/+ rats died suddenly, preceded by sinus bradycardia, advanced (second- and third-degree) AV block (N = 6), and/or ventricular tachycardia or fibrillation (N = 3). Sudden death was preceded by a further reduction of SCNA (3.22 ± 2.86 mV·s, P < .01) and sinus bradycardia (243 ± 55 bpm, P < .01). Histologic studies in CKD rats showed myocardial calcification that involved the conduction system. Chemical sympathectomy resulted in progressive reduction of SCNA over 7 days. CONCLUSION: SCNA can be used to estimate sympathetic tone in ambulatory rats. CKD is associated with reduced HR response to SCNA and conduction system diseases. Abrupt reduction of sympathetic tone precedes AV block, ventricular arrhythmia, and sudden death of CKD rats

A study of employee affective organisational commitment and retention in Pakistan:the roles of psychological contract breach and norms of reciprocity

Social exchange theory and notions of reciprocity have long been assumed to explain the relationship between psychological contract breach and important employee outcomes. To date, however, there has been no explicit testing of these assumptions. This research, therefore, explores the mediating role of negative, generalized, and balanced reciprocity, in the relationships between psychological contract breach and employees’ affective organizational commitment and turnover intentions. A survey of 247 Pakistani employees of a large public university was analyzed using structural equation modeling and bootstrapping techniques, and provided excellent support for our model. As predicted, psychological contract breach was positively related to negative reciprocity norms and negatively related to generalized and balanced reciprocity norms. Negative and generalized (but not balanced) reciprocity were negatively and positively (respectively) related to employees’ affective organizational commitment and fully mediated the relationship between psychological contract breach and affective organizational commitment. Moreover, affective organizational commitment fully mediated the relationship between generalized and negative reciprocity and employees’ turnover intentions. Implications for theory and practice are discussed

Brexit and the everyday politics of emotion: methodological lessons from history

The 2016 European Union referendum campaign has been depicted as a battle between ‘heads’ and ‘hearts’, reason and emotion. Voters’ propensity to trust their feelings over expert knowledge has sparked debate about the future of democratic politics in what is increasingly believed to be an ‘age of emotion’. In this article, we argue that we can learn from the ways that historians have approached the study of emotions and everyday politics to help us make sense of this present moment. Drawing on William Reddy’s concept of ‘emotional regimes’, we analyse the position of emotion in qualitative, ‘everyday narratives’ about the 2016 European Union referendum. Using new evidence from the Mass Observation Archive, we argue that while reason and emotion are inextricable facets of political decision-making, citizens themselves understand the two processes as distinct and competing

Clinically Actionable Hypercholesterolemia and Hypertriglyceridemia in Children with Nonalcoholic Fatty Liver Disease

OBJECTIVE: To determine the percentage of children with nonalcoholic fatty liver disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or triglycerides was indicated based on National Heart, Lung, and Blood Institute guidelines. STUDY DESIGN: This multicenter, longitudinal cohort study included children with NAFLD enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. Fasting lipid profiles were obtained at diagnosis. Standardized dietary recommendations were provided. After 1 year, lipid profiles were repeated and interpreted according to National Heart, Lung, and Blood Institute Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction. Main outcomes were meeting criteria for clinically actionable dyslipidemia at baseline, and either achieving lipid goal at follow-up or meeting criteria for ongoing intervention. RESULTS: There were 585 participants, with a mean age of 12.8 years. The prevalence of children warranting intervention for low-density lipoprotein cholesterol at baseline was 14%. After 1 year of recommended dietary changes, 51% achieved goal low-density lipoprotein cholesterol, 27% qualified for enhanced dietary and lifestyle modifications, and 22% met criteria for pharmacologic intervention. Elevated triglycerides were more prevalent, with 51% meeting criteria for intervention. At 1 year, 25% achieved goal triglycerides with diet and lifestyle changes, 38% met criteria for advanced dietary modifications, and 37% qualified for antihyperlipidemic medications. CONCLUSIONS: More than one-half of children with NAFLD met intervention thresholds for dyslipidemia. Based on the burden of clinically relevant dyslipidemia, lipid screening in children with NAFLD is warranted. Clinicians caring for children with NAFLD should be familiar with lipid management

In Children with Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis is Associated with Advanced Fibrosis

Background & Aims Focal zone 1 steatosis, although rare in adults with nonalcoholic fatty liver disease (NAFLD), does occur in children with NAFLD. We investigated whether focal zone 1 steatosis and focal zone 3 steatosis are distinct subphenotypes of pediatric NAFLD. We aimed to determine associations between the zonality of steatosis and demographic, clinical, and histologic features in children with NAFLD. Methods We performed a cross-sectional study of baseline data from 813 children (age <18 years; mean age, 12.8 ± 2.7 years). The subjects had biopsy-proven NAFLD and were enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network. Liver histology was reviewed using the Nonalcoholic Steatohepatitis Clinical Research Network scoring system. Results Zone 1 steatosis was present in 18% of children with NAFLD (n = 146) and zone 3 steatosis was present in 32% (n = 244). Children with zone 1 steatosis were significantly younger (10 vs 14 years; P < .001) and a significantly higher proportion had any fibrosis (81% vs 51%; P < .001) or advanced fibrosis (13% vs 5%; P < .001) compared with children with zone 3 steatosis. In contrast, children with zone 3 steatosis were significantly more likely to have steatohepatitis (30% vs 6% in children with zone 1 steatosis; P < .001). Conclusions Children with zone 1 or zone 3 distribution of steatosis have an important subphenotype of pediatric NAFLD. Children with zone 1 steatosis are more likely to have advanced fibrosis and children with zone 3 steatosis are more likely to have steatohepatitis. To achieve a comprehensive understanding of pediatric NAFLD, studies of pathophysiology, natural history, and response to treatment should account for the zonality of steatosis

Taxonomy based on science is necessary for global conservation

Peer reviewe