Electrocardiographic changes during haemodialysis and the potential impact on subcutaneous implantable cardioverter defibrillator eligibility.

INTRODUCTION: Haemodialysis patients who require defibrillator therapy are expected to benefit from the entirely avascular subcutaneous defibrillator (S-ICD), but haemodialysis is associated with dynamic changes in R and T wave amplitude which can impact S-ICD eligibility. A continuous assessment of S-ICD eligibility during haemodialysis has not previously been performed. MATERIAL AND METHODS: Continuous surface ECG recordings were obtained from a cohort of patients undergoing maintenance haemodialysis, but without an indication for an ICD. Automated vector screening was retrospectively performed at one-minute intervals throughout the dialysis session. Variations in S-ICD eligibility were calculated and in vectors with high degrees of variation, the underlying mechanism was identified. RESULTS: 72 vector recordings (mean duration 254.1 ± 6.0 min) were obtained from 24 patients (mean age 64.3 ± 5.5 years, 68% male). At the start of haemodialysis 47 vectors were S-ICD eligible (65.2%). At the end of session, all of these vectors had remained eligible, and an additional 6 vectors had also become eligible (73.6%). High vector score variability was observed in 7 patients and the commonest cause was a progressive change in R:T ratio (71.5%). CONCLUSION: In a haemodialysis population, a single haemodialysis session can be associated with a potential change in S-ICD eligibility in 8.4% of vectors, with up to 12.5% of vectors showing high degrees of variability, most commonly due to variations in R:T ratio. In an S-ICD population with similar characteristics S-ICD screening prior to haemodialysis would be expected to more accurately identify vectors that retain eligibility.

Characterising user engagement with mHealth for chronic disease self-management and impact on machine learning performance.

Mobile Health (mHealth) has the potential to be transformative in the management of chronic conditions. Machine learning can leverage self-reported data collected with apps to predict periods of increased health risk, alert users, and signpost interventions. Despite this, mHealth must balance the treatment burden of frequent self-reporting and predictive performance and safety. Here we report how user engagement with a widely used and clinically validated mHealth app, myCOPD (designed for the self-management of Chronic Obstructive Pulmonary Disease), directly impacts the performance of a machine learning model predicting an acute worsening of condition (i.e., exacerbations). We classify how users typically engage with myCOPD, finding that 60.3% of users engage frequently, however, less frequent users can show transitional engagement (18.4%), becoming more engaged immediately ( < 21 days) before exacerbating. Machine learning performed better for users who engaged the most, however, this performance decrease can be mostly offset for less frequent users who engage more near exacerbation. We conduct interviews and focus groups with myCOPD users, highlighting digital diaries and disease acuity as key factors for engagement. Users of mHealth can feel overburdened when self-reporting data necessary for predictive modelling and confidence of recognising exacerbations is a significant barrier to accurate self-reported data. We demonstrate that users of mHealth should be encouraged to engage when they notice changes to their condition (rather than clinically defined symptoms) to achieve data that is still predictive for machine learning, while reducing the likelihood of disengagement through desensitisation.

The NF-κB subunit c-Rel stimulates cardiac hypertrophy and fibrosis.

Cardiac remodeling and hypertrophy are the pathological consequences of cardiovascular disease and are correlated with its associated mortality. Activity of the transcription factor NF-κB is increased in the diseased heart; however, our present understanding of how the individual subunits contribute to cardiovascular disease is limited. We assign a new role for the c-Rel subunit as a stimulator of cardiac hypertrophy and fibrosis. We discovered that c-Rel-deficient mice have smaller hearts at birth, as well as during adulthood, and are protected from developing cardiac hypertrophy and fibrosis after chronic angiotensin infusion. Results of both gene expression and cross-linked chromatin immunoprecipitation assay analyses identified transcriptional activators of hypertrophy, myocyte enhancer family, Gata4, and Tbx proteins as Rel gene targets. We suggest that the p50 subunit could limit the prohypertrophic actions of c-Rel in the normal heart, because p50 overexpression in H9c2 cells repressed c-Rel levels and the absence of cardiac p50 was associated with increases in both c-Rel levels and cardiac hypertrophy. We report for the first time that c-Rel is highly expressed and confined to the nuclei of diseased adult human hearts but is restricted to the cytoplasm of normal cardiac tissues. We conclude that c-Rel-dependent signaling is critical for both cardiac remodeling and hypertrophy. Targeting its activities could offer a novel therapeutic strategy to limit the effects of cardiac disease.

Exploring the Validity of GOLD 2023 Guidelines: Should GOLD C and D Be Combined?

Introduction: The GOLD (Global Initiative for Chronic Obstructive Lung Disease) 2023 guidelines proposed important changes to the stratification of disease severity using the "ABCD" assessment tool. The highest risk groups "C" and "D" were combined into a single category "E" based on exacerbation history, no longer considering symptomology. Purpose: We quantify the differential disease progression of individuals initially stratified by the GOLD 2022 "ABCD" scheme to evaluate these proposed changes. Patients and Methods: We utilise data collected from 1529 users of the myCOPD mobile app, a widely used and clinically validated app supporting people living with COPD in the UK. For patients in each GOLD group, we quantify symptoms using COPD Assessment Tests (CAT) and rate of exacerbation over a 12-month period post classification. Results: CAT scores for users initially classified into GOLD C and GOLD D remain significantly different after 12 months (Kolmogorov-Smirnov statistic = 0.59, P = 8.2 × 10-23). Users initially classified into GOLD C demonstrate a significantly lower exacerbation rate over the 12 months post classification than those initially in GOLD D (Kolmogorov-Smirnov statistic = 0.26; P = 3.1 × 10-2; all exacerbations). Further, those initially classified as GOLD B have higher CAT scores and exacerbation rates than GOLD C in the following 12 months. Conclusion: CAT scores remain important for stratifying disease progression both in-terms of symptomology and future exacerbation risk. Based on this evidence, the merger of GOLD C and GOLD D should be reconsidered.

Tomato Brown Rugose Fruit Virus: Survival and Disinfection Efficacy on Common Glasshouse Surfaces.

Tomato brown rugose fruit virus (ToBRFV) is a contact-transmitted tobamovirus affecting many tomato growing regions of the world. This study investigated the effects of different glasshouse surfaces on the survival of the virus; the efficacy of different disinfectants; and heat treatment against ToBRFV (surfaces included steel, aluminium, hard plastic, polythene, glass and concrete). A bioassay followed by ELISA was used to check virus viability. ToBRFV survived for at least 7 days on all surfaces tested and on some for at least 6 months. The virus survived for over two hours on hands and gloves. Hand washing was shown to be unreliable for the removal of the virus. Glutaraldehyde and quaternary ammonium compound disinfectants were effective at one hour on all surfaces. Some other disinfectants were effective at one hour of contact time, on all surfaces except concrete. Sodium hypochlorite was partially effective against ToBRFV, even on concrete. A 5 min soak of plastic trays in water at 90 °C was effective at denaturing ToBRFV; however, 5 min at 70 °C was not. Heating infected sap showed the thermal inactivation point to be 90 °C, confirming the hot water treatment results and showing that deactivation was due to the heat treatment and not a washing effect of the water.

Differential expression of claudin tight junction proteins in the human cortical nephron.

BACKGROUND: In renal tubules, paracellular permeability is tightly controlled to facilitate solute absorption and urinary concentration and is regulated by tight junctions, which incorporate claudin proteins. There is very limited information confirming the localization of these proteins in the human renal cortex. Most data is inferred from mouse, bovine and rabbit studies and differences exist between mouse and other species. METHODS: A survey of claudin staining was performed on human kidney cortex embedded in glycolmethacrylate resin to enhance tissue morphology and facilitate the cutting of 2 microm serial sections. RESULTS: Claudin-2, -10 and -11 antibodies labelled renal tubular epithelial cells, correlating with Lotus tetragonolobus and N-cadherin positive proximal tubules. Claudin-3, -10, -11 and -16 antibodies strongly stained a population of tubules that were positive for Tamm Horsfall protein on adjacent sections, confirming expression in the thick ascending limb of the Loop of Henle. Claudin-3, -4 and -8 antibodies reacted with tubules that correlated with the distal nephron markers, E-cadherin, epithelial membrane antigen and Dolichos biflorus and claudin-3, -4, -7 and -8 with the distal tubule marker, calbindin, and the collecting duct marker, aquaporin-2. Claudin-14 was localized in distal convoluted tubules, correlating positively with calbindin but negatively with aquaporin-2, whereas claudin-1 staining was identified in the parietal epithelium of Bowman's capsule, distal convoluted tubule and collecting duct. Cellular and tight junction localization of claudin staining in renal tubules was heterogeneous and is discussed. CONCLUSIONS: Complex variation in the expression of human claudins likely determines paracellular permeability in the kidney. Altered claudin expression may influence pathologies involving abnormalities of absorption.

Key experiences of primary social groups in Unspecified Kidney Donation.

BACKGROUND: The role of family members in directed kidney donation is well documented in the literature from both a physiological and psychosocial perspective. The experiences of families, or primary social groups (PSGs), where one member considers donating a kidney via unspecified altruistic kidney donation route (UKD) is poorly understood. This is pertinent as lack of family support has been identified as a potential contributor to donation withdrawal. OBJECTIVES: This study aimed to explore the relevant psychosocial factors underpinning completed and uncompleted donations. DESIGN: A qualitative study using semi-structured interviews. PARTICIPANTS: Qualitative interviews were conducted in the United Kingdom with 35 individuals comprising of: 11 donors who donated their kidney altruistically and 8 of their PSG members, and 11 donors who withdrew and 5 of their PSG members. APPROACH: Interviews were transcribed verbatim and analysed using Framework Analysis. RESULTS: Two major themes were identified: (1) Supportability, which contained experiences fundamental to proceeding to donate, underpinned by four subthemes Acceptability, Awareness and Information, Family Risk and Ambivalence;(2) Seeking Resolution, contained discussions of experiences following either withdrawal from or completion of the donation, and comprised two sub-themes, Unfinished Business and Resolve. CONCLUSIONS: There are key differences in the experiences between those who completed their donation and those who withdrew. It is clear from this study that UKD operates within a PSG's social framework. Clinical implications suggest interventions at the level of addressing ambivalence within the PSG and the need for promotion of better psychosocial outcomes both following completion or withdrawal from donation.

Racial and social disparities in the access to automated peritoneal dialysis - results of a national PD cohort.

The prevalence of patients on automated peritoneal dialysis (APD) is increasing worldwide and may be guided by clinical characteristics, financial issues and patient option. Whether socioeconomic factors at the patient level may influence the decision for the initial peritoneal dialysis (PD) modality is unknown. This is a prospective cohort study. The primary outcome of interest was the probability to start PD on APD. The inclusion criteria were adult patients incident in PD. Exclusion criteria were missing data for either race or initial PD modality. We used a mixed-model analysis clustering patients according to their PD center and region of the country. We included 3,901 patients of which 1,819 (46.6%) had APD as their first modality. We found a significant disparity for race and educational level with African American patients less likely to start on APD (Odds ratio 0.74 CI95% 0.58-0.94) compared to Whites whilst those with greater educational levels were more likely to start on APD (Odds ratio 3.70, CI95% 2.25-6.09) compared to illiterate patients. Limiting the use of APD in disadvantaged population may be unethical. Demographics and socioeconomic status should not be necessarily part of the decision-making process of PD modality choice.

Enhanced immunohistochemical resolution of claudin proteins in glycolmethacrylate-embedded tissue biopsies.

There are a number of disadvantages with conventional tissue immunohistochemistry for accurate -localisation of claudin proteins. Traditionally, tissue cryopreservation or formaldehyde fixation with wax embedding is utilised prior to sectioning and antibody localisation. Wax embedding gives better morphological preservation than frozen tissue, but the required use of chemical cross-linking fixatives renders many antigens inaccessible to antibody binding or results in subsequent disruption of antibody localisation patterns due to the use of harsh antigen retrieval methods. Use of frozen or wax-embedded tissue also requires the cutting of relatively thick>6-µm sections, making the interrogation of serial sections very limited. The use of glycolmethacrylate (GMA) tissue embedding with fixation in acetone is compatible with epitope preservation for many antibody reagents that are often destroyed by chemical cross-linking fixatives. GMA is a water-miscible embedding resin that maintains tissue hydration during processing, thus reducing tissue shrinkage, while embedding and cutting in the polymerised resin physically supports the tissue, thus improving morphology. This method also facilitates the cutting of 2-µm sequential sections for analysis of multiple antigens and maximises the information available from small tissue biopsies from human clinical sources.