Stroke in UK Biobank (UKB) is ascertained
linkages to coded administrative datasets and self-report. We studied the accuracy of these codes using genetic validation.
We compiled stroke-specific and ...broad cerebrovascular disease (CVD) code lists (Read V2/V3, ICD-9/-10) for medical settings (hospital, death record, primary care) and self-report. Among 408,210 UKB participants, we identified all with a relevant code, creating 12 stroke definitions based on the code type and source. We performed genome-wide association studies (GWASs) for each definition, comparing summary results against the largest published stroke GWAS (MEGASTROKE), assessing genetic correlations, and replicating 32 stroke-associated loci.
The stroke case numbers identified varied widely from 3,976 (primary care stroke-specific codes) to 19,449 (all codes, all sources). All 12 UKB stroke definitions were significantly correlated with the MEGASTROKE summary GWAS results (rg.81-1) and each other (rg.4-1). However, Bonferroni-corrected confidence intervals were wide, suggesting limited precision of some results. Six previously reported stroke-associated loci were replicated using ≥1 UKB stroke definition.
Stroke case numbers in UKB depend on the code source and type used, with a 5-fold difference in the maximum case-sample size. All stroke definitions are significantly genetically correlated with the largest stroke GWAS to date.
Adequate levels of folate are crucial for human development. MTHFR (Methylene tetrahydrofolate reductase) is involved in the metabolism of folic acid and other B vitamins. The aim of this work is to ...examine the allele frequency and haplotype distribution of MTHFR-C677T and MTHFR-A1298C polymorphisms in two independent samples (NorthEast Spanish and North-Western Siberia). The degree of population differentiation and signatures of positive selection were also examined in 18 world populations. The samples comprised 623 Spanish individuals and 172 Ob-Ugric people (Khanty and Mansi). The Spanish sample showed 44% individuals with 30% reduced enzyme activity, and 16% people with 70% reduced activity; whereas the Khanty sample revealed only 3% people with 70% reduced activity. In the 18 populations screened, we found significant South to North clines for SNPs and haplotypes. Overall, we failed to detect any traces of positive selection. The high frequency of people with reduced MTHFR enzyme activity in Spain highlights the need for diets rich in folate and folic acid supplementation in some groups. The low frequency of individuals with reduced enzymatic activity among the Khanty together with their traditional diet indicates a protective combination against pathologies related to folic acid deficiencies.
A series of adamantane‐containing molecules consisting of two lipophilic centers which are linked by different bridges (oxime esters, oxime ethers, amides, and symmetric alcohols), were designed and ...synthesized as anti‐inflammatory agents. Their anti‐inflammatory activity was evaluated as their ability to inhibit phlogistic‐induced mouse paw edema. Some of the tested compounds exhibited activity comparable to that of diclofenac, others had a weaker activity, while some oxime esters proved to enhance the inflammatory response. In all cases, activity was dose‐dependent. The deacylated compound 10 was found to be the most active of the series, inhibiting inflammation due to Baker’s yeast, the mechanism of which involves mainly the activation of lipoxy‐genase and/or complement systems, a property which is absent from most selective cyclooxygenase only inhibiting non‐steroidal anti‐inflammatory drugs (NSAIDs).
Presently, the penetration of residential distributed energy resources (DER) that produce (photovoltaics, wind generators) or consume (electric heat pumps, electric vehicles) electric power, is ...continuously increasing in an uncoordinated fashion. If the appropriate steps are not taken to ensure their smooth integration, issues such as violations of voltage and thermal limits occur, especially at higher DER penetrations. This study investigates the impact of each DER on low-voltage (LV) networks, and subsequently, multiple large-scale demand side flexibility (DSF) schemes are proposed per DER type, based on the cooperation of system operator and residential customer, to combat said issues and to significantly increase DER penetration. A rule-based approach is used for each DSF scheme, to highlight their effectiveness in ‘raw’ form, and to assess whether they merit further practical consideration. Using data on real LV feeders and real DER profiles, through a Monte Carlo simulation framework considering the stochastic behaviour of the various network elements, DER impact and DSF performance are measured. The results include a major improvement in delivered power quality, highly increased DER accommodation capacity, a thorough comparison of the technical performance of each DSF scheme, and a conclusion on the effectiveness of each DSF scheme.
Cardiovascular disease is commonly accompanied by renal dysfunction. Multimorbidity in hospitalized patients impacts unfavorably on prognosis and hospital stay. We aimed to illustrate the ...contemporary burden of cardiorenal morbidity across inpatient cardiology care in Greece.
The Hellenic Cardiorenal Morbidity Snapshot (HECMOS) used an electronic platform to collect demographic and clinically relevant information about all patients hospitalized on March 3, 2022, in Greece. The participating institutions covered all levels of inpatient cardiology care and most of the country’s territories to collect a real-world, nation representative sample.
A total of 923 patients (men 68.4%, median age 73 ± 14.8 years) were admitted to 55 different cardiology departments. 57.7% of the participants were aged >70 years. Hypertension was highly prevalent and present in 66% of the cases. History of chronic HF, diabetes mellitus, atrial fibrillation, and chronic kidney disease was present in 38%, 31.8%, 30%, and 26%, respectively. Furthermore, 64.1% of the sample exhibited at least one of these 4 entities. Accordingly, a combination of ≥2 of these morbid conditions was recorded in 38.7%, of ≥3 in 18.2%, whereas 4.3% of the sample combined all 4 in their medical history. The most common combination was the coexistence of heart failure-atrial fibrillation accounting for 20.6% of the sample. Nine of 10 nonelectively admitted patients were hospitalized due to acute HF (39.9%), acute coronary syndrome (33.5%), or tachyarrhythmias (13.2%).
HECMOS participants carried a remarkable burden of cardio-reno-metabolic disease. HF in conjunction with atrial fibrillation was found to be the most prevalent combination among the studied cardiorenal nexus of morbidities in the whole study population.
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