Children with CKD rate their HRQOL lower than the healthy controls do. It may be reassuring to caregivers that children on dialysis rate their HRQOL higher than would be expected. However, it is of some concern that caregiver perception of improved HRQOL following transplantation was not shared by their children in the present study.

Diabetic cardiomyopathy (DCM) is defined as cardiac disease independent of vascular complications during diabetes. The number of new cases of DCM is rising at epidemic rates in proportion to newly diagnosed cases of diabetes mellitus (DM) throughout the world. DCM is a heart failure syndrome found in diabetic patients that is characterized by left ventricular hypertrophy and reduced diastolic function, with or without concurrent systolic dysfunction, occurring in the absence of hypertension and coronary artery disease. DCM and other diabetic complications are caused in part by elevations in blood glucose and lipids, characteristic of DM. Although there are pathological consequences to hyperglycemia and hyperlipidemia, the combination of the two metabolic abnormalities potentiates the severity of diabetic complications. A natural competition exists between glucose and fatty acid metabolism in the heart that is regulated by allosteric and feedback control and transcriptional modulation of key limiting enzymes. Inhibition of these glycolytic enzymes not only controls flux of substrate through the glycolytic pathway, but also leads to the diversion of glycolytic intermediate substrate through pathological pathways, which mediate the onset of diabetic complications. The present review describes the limiting steps involved in the development of these pathological pathways and the factors involved in the regulation of these limiting steps. Additionally, therapeutic options with demonstrated or postulated effects on DCM are described.

In contrast to laryngoscopy, the ease of intubation using the Trachlight does not appear to be influenced by anatomic variations of the upper airway. Intubation occasionally failed with the Trachlight but in all cases was resolved with direct laryngoscopy. The failures of direct laryngoscopy were resolved with Trachlight. Thus the combined technique was 100% successful in intubating the tracheas of all patients.

During the cardiac cycle, the release of Ca2+ from the sarcoplasmic reticulum (SR) through the ryanodine receptor (RyR2) channel complex is controlled by the levels of cytosolic and luminal Ca 2+ and alterations in these regulatory processes have been implicated in cardiac disease including arrhythmia.

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Non-technical summary Cardiac glycosides (CGs) have been routinely used in the treatment of congestive heart failure (HF). Unfortunately, the therapeutic use of CGs in treating HF is limited by their adverse side effects, including cardiac arrhythmias. The arrhythmic side effects of CGs have been traditionally ascribed to excessive cellular Ca 2+ retention (Ca 2+ overload) leading to spontaneous discharges of intracellular Ca 2+ stores, or Ca 2+ waves, in turn causing oscillations of the cardiac membrane potential. In the present study, we demonstrate that the proarrhythmic effects of CGs on Ca 2+ cycling in cardiac myocytes involve alterations in the function of ryanodine receptor calcium channels caused by oxidative changes in the channel structure by reactive oxygen species. Our findings reveal a new mechanism for CG-induced Ca 2+ waves and suggest a potential target for antiarrhythmic therapy in HF patients treated with CGs.Abstract The therapeutic use of cardiac glycosides (CGs), agents commonly used in treating heart failure (HF), is limited by arrhythmic toxicity. The adverse effects of CGs have been attributed to excessive accumulation of intracellular Ca 2+ resulting from inhibition of Na + /K + -ATPase ion transport activity. However, CGs are also known to increase intracellular reactive oxygen species (ROS), which could contribute to arrhythmogenesis through redox modification of cardiac ryanodine receptors (RyR2s). Here we sought to determine whether modification of RyR2s by ROS contributes to CG-dependent arrhythmogenesis and examine the relevant sources of ROS. In isolated rat ventricular myocytes, the CG digitoxin (DGT) increased the incidence of arrhythmogenic spontaneous Ca 2+ waves, decreased the sarcoplasmic reticulum (SR) Ca 2+ load, and increased both ROS and RyR2 thiol oxidation. Additionally, pretreatment with DGT increased spark frequency in permeabilized myocytes. These effects on Ca 2+ waves and sparks were prevented by the antioxidant N -(2-mercaptopropionyl) glycine (MPG). The CG-dependent increases in ROS, RyR2 oxidation and arrhythmogenic propensity were reversed by inhibitors of NADPH oxidase, mitochondrial ATP-dependent K + channels (mito-K ATP ) or permeability transition pore (PTP), but not by inhibition of xanthine oxidase. These results suggest that the arrhythmogenic adverse effects of CGs involve alterations in RyR2 function caused by oxidative changes in the channel structure by ROS. These CG-dependent effects probably involve release of ROS from mitochondria possibly mediated by NADPH oxidase.

Objectives To quantify the risk of death among people with rare autoimmune rheumatic diseases (RAIRD) during the UK 2020 COVID-19 pandemic compared with the general population, and compared with their pre-COVID risk. Methods We conducted a cohort study in Hospital Episode Statistics for England 2003 onwards, and linked data from the NHS Personal Demographics Service. We used ONS published data for general population mortality rates. Results We included 168 691 people with a recorded diagnosis of RAIRD alive on 01/03/2020. Their median age was 61.7 (IQR 41.5–75.4) years, and 118 379 (70.2%) were female. Our case ascertainment methods had a positive predictive value of 85%. 1,815 (1.1%) participants died during March and April 2020. The age-standardised mortality rate (ASMR) among people with RAIRD (3669.3, 95% CI 3500.4–3838.1 per 100 000 person-years) was 1.44 (95% CI 1.42–1.45) times higher than the average ASMR during the same months of the previous 5 years, whereas in the general population of England it was 1.38 times higher. Age-specific mortality rates in people with RAIRD compared with the pre-COVID rates were higher from the age of 35 upwards, whereas in the general population the increased risk began from age 55 upwards. Women had a greater increase in mortality rates during COVID-19 compared with men. Conclusion The risk of all-cause death is more prominently raised during COVID-19 among people with RAIRD than among the general population. We urgently need to quantify how much risk is due to COVID-19 infection and how much is due to disruption to healthcare services.