Structural insights into the human RyR2 N-terminal region involved in cardiac arrhythmias

Human ryanodine receptor 2 (hRyR2) mediates calcium release from the sarcoplasmic reticulum, enabling cardiomyocyte contraction. The N-terminal region of hRyR2 (amino acids 1–606) is the target of >30 arrhythmogenic mutations and contains a binding site for phosphoprotein phosphatase 1. Here, the solution and crystal structures determined under near-physiological conditions, as well as a homology model of the hRyR2 N-terminal region, are presented. The N-terminus is held together by a unique network of interactions among its three domains, A, B and C, in which the central helix (amino acids 410–437) plays a prominent stabilizing role. Importantly, the anion-binding site reported for the mouse RyR2 N-terminal region is notably absent from the human RyR2. The structure concurs with the differential stability of arrhythmogenic mutations in the central helix (R420W, I419F and I419F/R420W) which are owing to disparities in the propensity of mutated residues to form energetically favourable or unfavourable contacts. In solution, the N-terminus adopts a globular shape with a prominent tail that is likely to involve residues 545–606, which are unresolved in the crystal structure. Docking the N-terminal domains into cryo-electron microscopy maps of the closed and open RyR1 conformations reveals C atom movements of up to 8 A ° upon channel gating, and predicts the location of the leucine– isoleucine zipper segment and the interaction site for spinophilin and phosphoprotein phosphatase 1 on the RyR surface

Quality of Life in Patients with Diabetic Foot Ulcer in the Visegrad Countries

AIM AND OBJECTIVES: The aim of the present study was to identify the quality of life of patients with diabetic foot ulcers in the Visegrad countries. BACKGROUND: The diabetics with foot ulcers are principally evaluated on the basis of physical parameters, but this does not always reveal much about the patient's experience of life with ulceration. DESIGN: The cross-sectional study. METHODS: The standardized generic questionnaire World Health Organisation Quality of Life Bref was used. The sample was made up of 525 participants and the calculations were performed using the IBM SPSS statistical program. RESULTS: The significant negative correlations between demographic data such as age, duration of diabetes mellitus, duration of diabetes ulceration treatment and a lower level of quality of life were found across the sample. The statistically significant differences according to clinical characteristics such as Wagner classification, frequency of foot ulcers, present peripheral vascular diseas and pain in terms of quality of life were also revealed. Significant differences of quality of life among Visegrad countries were revealed: Hungary's participants had a worse quality of life than others, while Slovak participants expressed lower satisfaction with their health than Czech. CONCLUSIONS: Socio-demographic factors and clinical characteristics influence the quality of life of patients with diabetic foot ulcer. Significant differences between patients of Visegrad countries were found in all domains of quality of life: physical, psychological, social and environmental. RELEVANCE TO CLINICAL PRACTICE: The quality of life of patients with diabetic foot ulcer reflects the conditions and health care system in each of the Visegrad countries. We have to respect socio-demographic factors and clinical characteristics in nursing care. This could have an impact on managing patient care not only with regard to their diabetic foot ulcer but also with regard to the patient as a personality with their own problems in relation to physical, psychosocial and environmental conditions. This article is protected by copyright. All rights reserved

Structural insights into the human RyR2 N terminal region involved in cardiac arrhythmias

Human ryanodine receptor 2 hRyR2 mediates calcium release from the sarcoplasmic reticulum, enabling cardio myocyte contraction. The N terminal region of hRyR2 amino acids 1 606 is the target of gt;30 arrhythmogenic mutations and contains a binding site for phosphoprotein phosphatase 1. Here, the solution and crystal structures determined under near physiological conditions, as well as a homology model of the hRyR2 N terminal region, are presented. The N terminus is held together by a unique network of interactions among its three domains, A, B and C, in which the central helix amino acids 410 437 plays a prominent stabilizing role. Importantly, the anion binding site reported for the mouse RyR2 N terminal region is notably absent from the human RyR2. The structure concurs with the differential stability of arrhythmogenic mutations in the central helix R420W, I419F and I419F R420W which are owing to disparities in the propensity of mutated residues to form energetically favourable or unfavourable contacts. In solution, the N terminus adopts a globular shape with a prominent tail that is likely to involve residues 545 606, which are unresolved in the crystal structure. Docking the N terminal domains into cryo electron microscopy maps of the closed and open RyR1 conformations reveals C[alpha] atom movements of up to 8 upon channel gating, and predicts the location of the leucine isoleucine zipper segment and the interaction site for spinophilin and phosphoprotein phosphatase 1 on the RyR surfac

Examining the impact of a 9-component bundle and the INICC multidimensional approach on catheter-associated urinary tract infection rates in 32 countries across Asia, Eastern Europe, Latin America, and the Middle East

Background: Catheter-Associated Urinary Tract Infections (CAUTIs) frequently occur in the intensive care unit (ICU) and are correlated with a significant burden. Methods: We implemented a strategy involving a 9-element bundle, education, surveillance of CAUTI rates and clinical outcomes, monitoring compliance with bundle components, feedback of CAUTI rates and performance feedback. This was executed in 299 ICUs across 32 low- and middle-income countries. The dependent variable was CAUTI per 1,000 UC days, assessed at baseline and throughout the intervention, in the second month, third month, 4 to 15 months, 16 to 27 months, and 28 to 39 months. Comparisons were made using a 2-sample t test, and the exposure-outcome relationship was explored using a generalized linear mixed model with a Poisson distribution. Results: Over the course of 978,364 patient days, 150,258 patients utilized 652,053 UC-days. The rates of CAUTI per 1,000 UC days were measured. The rates decreased from 14.89 during the baseline period to 5.51 in the second month (risk ratio [RR] = 0.37; 95% confidence interval [CI] = 0.34-0.39; P < .001), 3.79 in the third month (RR = 0.25; 95% CI = 0.23-0.28; P < .001), 2.98 in the 4 to 15 months (RR = 0.21; 95% CI = 0.18-0.22; P < .001), 1.86 in the 16 to 27 months (RR = 0.12; 95% CI = 0.11-0.14; P < .001), and 1.71 in the 28 to 39 months (RR = 0.11; 95% CI = 0.09-0.13; P < .001). Conclusions: Our intervention, without substantial costs or additional staffing, achieved an 89% reduction in CAUTI incidence in ICUs across 32 countries, demonstrating feasibility in ICUs of low- and middle-income countries.Revisión por pare