Left ventricular hypertrophy and biomarkers of cardiac damage and stress in aortic stenosis

Background Left ventricular hypertrophy (LVH) is associated with increased mortality risk and rehospitalization after transcatheter aortic valve replacement among those with severe aortic stenosis. Whether cardiac troponin (cTnT) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) risk stratify patients with aortic stenosis and without LVH is unknown. Methods and Results In a multicenter prospective registry of 923 patients with severe aortic stenosis undergoing transcatheter aortic valve replacement, we included 674 with core-laboratory-measured LV mass index, cTnT, and NT-proBNP. LVH was defined by sex-specific guideline cut-offs and elevated biomarker levels were based on age and sex cut-offs. Adjusted Cox proportional hazards models evaluated associations between LVH and biomarkers and all-cause death out to 5 years. Elevated cTnT and NT-proBNP were present in 82% and 86% of patients with moderate/severe LVH, respectively, as compared with 66% and 69% of patients with no/mild LVH, respectively

Factors associated with clinical progression to severe COVID-19 in people with cystic fibrosis: A global observational study

BACKGROUND This international study aimed to characterise the impact of acute SARS-CoV-2 infection in people with cystic fibrosis and investigate factors associated with severe outcomes. Methods Data from 22 countries prior to 13$^{th}$ December 2020 and the introduction of vaccines were included. It was de-identified and included patient demographics, clinical characteristics, treatments, outcomes and sequalae following SARS-CoV-2 infection. Multivariable logistic regression was used to investigate factors associated with clinical progression to severe COVID-19, using the primary outcome of hospitalisation with supplemental oxygen. RESULTS SARS-CoV-2 was reported in 1555 people with CF, 1452 were included in the analysis. One third were aged 70%: a 17-fold increase in odds. Worse outcomes were independently associated with older age, non-white race, underweight body mass index, and CF-related diabetes. Prescription of highly effective CFTR modulator therapies was associated with a significantly reduced odds of being hospitalised with oxygen (AOR 0.43 95%CI 0.31-0.60 p<0.001). Transplanted patients were hospitalised with supplemental oxygen therapy (21.9%) more often than non-transplanted (8.8%) and was independently associated with the primary outcome (Adjusted OR 2.45 95%CI 1.27-4.71 p=0.007). CONCLUSIONS This is the first study to show that there is a protective effect from the use of CFTR modulator therapy and that people with CF from an ethnic minority are at more risk of severe infection with SARS-CoV-2

A Hierarchical Model for the Ages of Galactic Halo White Dwarfs

In astrophysics, we often aim to estimate one or more parameters for each member object in a population and study the distribution of the fitted parameters across the population. In this paper, we develop novel methods that allow us to take advantage of existing software designed for such case-by-case analyses to simultaneously fit parameters of both the individual objects and the parameters that quantify their distribution across the population. Our methods are based on Bayesian hierarchical modelling which is known to produce parameter estimators for the individual objects that are on average closer to their true values than estimators based on case-by-case analyses. We verify this in the context of estimating ages of Galactic halo white dwarfs (WDs) via a series of simulation studies. Finally, we deploy our new techniques on optical and near-infrared photometry of ten candidate halo WDs to obtain estimates of their ages along with an estimate of the mean age of Galactic halo WDs of 12.11 +0.85-0.86 Gyr. Although this sample is small, our technique lays the ground work for large-scale studies using data from the Gaia mission

Multi-trait genome-wide association study of opioid addiction: OPRM1 and beyond

Opioid addiction (OA) is moderately heritable, yet only rs1799971, the A118G variant in OPRM1, has been identified as a genome-wide significant association with OA and independently replicated. We applied genomic structural equation modeling to conduct a GWAS of the new Genetics of Opioid Addiction Consortium (GENOA) data together with published studies (Psychiatric Genomics Consortium, Million Veteran Program, and Partners Health), comprising 23,367 cases and effective sample size of 88,114 individuals of European ancestry. Genetic correlations among the various OA phenotypes were uniformly high (

Prevalence of vitamin D deficiency and association with metabolic syndrome in a Qatari population

Background/Objectives Despite long hours of sunlight in Qatar and other regions of the Middle East, vitamin D deficiency has been rising. In parallel, the prevalence metabolic syndrome has also been increasing in Qatar. Vitamin D levels have been associated with metabolic syndrome but data are inconsistent and no studies have addressed these inter-relationships in a Middle Eastern population where the prevalence of these conditions is high. The objective is to investigate the prevalence of vitamin D deficiency and its association with metabolic syndrome and its components in the Qatar Biobank population. Subjects/Methods A cross-sectional study of 1 205 participants (702 women and 503 men) from the Qatar Biobank, comprising Qataris and non-Qataris between the ages of 18 to 80 years, was used to perform multivariate linear regression analyses to examine the association between metabolic syndrome and prevalence of vitamin D deficiency (defined as <20 ng/mL serum vitamin D levels) adjusting for age, sex, ethnicity, season of blood collection, physical activity, and education. Odds ratios and 95% confidence intervals were calculated for all analyses. Results Approximately 64% of participants were vitamin D deficient (<20 ng/mL) with more men being deficient (68.6%) than women (61.3%). Serum vitamin D was 8% lower in individuals with metabolic syndrome (RR: 0.92, 95%CI: 0.87 – 0.98, p-value: 0.01) compared to individuals without metabolic syndrome. Waist circumference and HDL as well as high triglyceride levels were also significantly positively associated with vitamin D deficiency. No association was found between the other components of metabolic syndrome or diabetes and the presence of vitamin D deficiency. Conclusions Vitamin D deficiency is prevalent in this Qatari population. Presence of metabolic syndrome was associated with presence of vitamin D deficiency. Future prospective studies need to be conducted to investigate the potential for causality

Capacity for the management of kidney failure in the International Society of Nephrology Africa region:Report from the 2023 ISN Global Kidney Atlas (ISN-GKHA)

The burden of chronic kidney disease (CKD) and associated risk of kidney failure are increasing in Africa. The management of people with CKD is fraught with numerous challenges because of limitations in health systems and infrastructures for care delivery. From the third iteration of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA), we describe the status of kidney care in the ISN Africa region using the World Health Organization building blocks for health systems. We identified limited government health spending which in turn led to increased out-of-pocket costs for people with kidney disease at the point of service delivery. The healthcare workforce across Africa was sub-optimal and further challenged by the exodus of trained healthcare workers out of the continent. Medical products, technologies, and services for the management of people with non-dialysis CKD and for kidney replacement therapy (KRT) were scarce due to limitations in health infrastructure that was inequitably distributed. There were few kidney registries and advocacy groups championing kidney disease management in Africa compared to the rest of the world. Strategies for ensuring improved kidney care in Africa include focusing on CKD prevention and early detection, improving the effectiveness of the available healthcare workforce (e.g., multidisciplinary teams, task substitution, and telemedicine), augmenting kidney care financing, providing quality, up-to-date health information data, and improving the accessibility, affordability, and delivery of quality treatment (KRT or conservative kidney management) for all people living with kidney failure

Asymptomatic Phytoplasma Reveal a Novel and Troublesome Infection

Asymptomatic infections are by their nature challenging to study and even more difficult to monitor across broad geographical ranges, particularly as methods are reliant on expensive molecular techniques. The plant pathogen that causes Witches’ Broom disease of lime (Candidatus Phytoplasma aurantifolia) is a major limiting factor in lime production across the Middle East and was recently detected in Brazil, but without the typical symptoms from the Middle East. Here, we discuss the difficulty of monitoring asymptomatic infections and highlight the threat posed by highlight future outbreaks. Asymptomatic infections have important implications for understanding the evolution of pathogens within perennial hosts. We use three model systems of asymptomatic infections: (i) a Phytoplasma and (ii) a bacterial infection of lime (Citrus aurantifolia) and (iii) an “out-group” Phytoplasma of Cassava (Manihot esculenta) to demonstrate consistency across divergent hosts. We found that although all plants in the study were intentionally infected, assays typically did not confirm this diagnosis. Emergent technologies monitoring gene expression could be used to both study novel biology associated with asymptomatic infections and develop monitoring technologies. We highlight the difficulty of monitoring asymptomatic infections in possible future outbreaks and have important implications for understanding the evolution of pathogens within perennial hosts

Microchannel neural interface manufacture by stacking silicone and metal foil laminae

Objective: Microchannel neural interfaces (MNIs) overcome problems with recording from peripheral nerves by amplifying signals independent of Node of Ranvier position. Selective recording and stimulation using an MNI requires good insulation between microchannels and a high electrode density. We propose that stacking microchannel laminae will improve selectivity over single layer MNI designs due to the increase in electrode number and an improvement in microchannel sealing. Approach: This paper describes a manufacturing method for creating MNIs which overcomes limitations on electrode connectivity and microchannel sealing. Laser cut silicone – metal foil laminae were stacked using plasma bonding to create an array of microchannels containing tripolar electrodes. Electrodes were DC etched and electrode impedance and cyclic voltammetry were tested. Main results: MNIs with 100 µm and 200 µm diameter microchannels were manufactured. High electrode density MNIs are achievable with electrodes present in every microchannel. Electrode impedances of 27.2 ± 19.8 kΩ at 1kHz were achieved. Following 2 months of implantation in Lewis rat sciatic nerve, micro-fascicles were observed regenerating through the MNI microchannels. Significance: Selective microchannel neural interfaces with the peripheral nervous system may allow upper limb amputees to control prostheses intuitively