Somatic Mosaic Chromosomal Alterations and Death of Cardiovascular Disease Causes among Cancer Survivors.

BACKGROUND: Cancer survivors are at an increased risk of cardiovascular disease (CVD) compared with the general population. We sought to evaluate the impact of mosaic chromosomal alterations (mCA) on death of CVD causes, coronary artery disease (CAD) causes, and of any cause in patients with a cancer diagnosis. METHODS: The study was a prospective cohort analysis of 48,919 UK Biobank participants with a cancer diagnosis. mCAs were characterized using DNA genotyping array intensity data and long-range chromosomal phase inference. Multivariable Cox regression models were used to ascertain the associations of mCAs. Exploratory endpoints included various incident cardiovascular phenotypes. RESULTS: Overall, 10,070 individuals (20.6%) carried ≥ 1 mCA clone. In adjusted analyses, mCA was associated with an increased risk of death of CAD causes [HR, 1.37; 95% confidence interval (CI), 1.09-1.71; P = 0.006]. In sub-analyses, we found that carriers of mCAs diagnosed with kidney cancer had an increased risk of death of CVD causes (HR, 2.03; 95% CI, 1.11-3.72; P = 0.022) and CAD causes (HR, 3.57; 95% CI, 1.44-8.84; P = 0.006). Women diagnosed with breast cancer who carried a mCA also had a higher risk of death of CAD causes (HR, 2.46; 95% CI, 1.23-4.92; P = 0.011). CONCLUSIONS: Among cancer survivors, carriers of any mCA are at an increased risk of CAD death compared with noncarriers. Mechanistic studies should be considered to better ascertain the biological mechanisms underneath the observed associations between mCAs and cardiovascular events for specific cancer types. IMPACT: There may be clinical relevance in considering mCAs in patients diagnosed with cancer and undergoing treatment.

Construction of a femininity score in the UK Biobank and its association with angina diagnosis prior to myocardial infarction.

Gender captures social components beyond biological sex and can add valuable insight to health studies in populations. However, assessment of gender typically relies on questionnaires which may not be available. The aim of this study is to construct a gender metric using available variables in the UK Biobank and to apply it to the study of angina diagnosis. Proxy variables for femininity characteristics were identified in the UK Biobank and regressed on sex to construct a composite femininity score (FS) validated using tenfold cross-validation. The FS was assessed as a predictor of angina diagnosis before incident myocardial infarction (MI) events. The FS was derived for 315,937 UK Biobank participants. In 3059 individuals with no history of MI at study entry who had an incident MI event, the FS was a significant predictor of angina diagnosis prior to MI (OR 1.24, 95% CI 1.10-1.39, P < 0.001) with a significant sex-by-FS interaction effect (P = 0.003). The FS was positively associated with angina diagnosis prior to MI in men (OR 1.37, 95% CI 1.19-1.57, P < 0.001), but not in women. We have provided a new tool to conduct gender-sensitive analyses in observational studies, and applied it to study of angina diagnosis prior to MI.

Genetics of symptom remission in outpatients with COVID-19.

We conducted a genome-wide association study of time to remission of COVID-19 symptoms in 1723 outpatients with at least one risk factor for disease severity from the COLCORONA clinical trial. We found a significant association at 5p13.3 (rs1173773; P = 4.94 × 10-8) near the natriuretic peptide receptor 3 gene (NPR3). By day 15 of the study, 44%, 54% and 59% of participants with 0, 1, or 2 copies of the effect allele respectively, had symptom remission. In 851 participants not treated with colchicine (placebo), there was a significant association at 9q33.1 (rs62575331; P = 2.95 × 10-8) in interaction with colchicine (P = 1.19 × 10-5) without impact on risk of hospitalisations, highlighting a possibly shared mechanistic pathway. By day 15 of the study, 46%, 62% and 64% of those with 0, 1, or 2 copies of the effect allele respectively, had symptom remission. The findings need to be replicated and could contribute to the biological understanding of COVID-19 symptom remission.

A genetic model of ivabradine recapitulates results from randomized clinical trials.

BACKGROUND: Naturally occurring human genetic variants provide a valuable tool to identify drug targets and guide drug prioritization and clinical trial design. Ivabradine is a heart rate lowering drug with protective effects on heart failure despite increasing the risk of atrial fibrillation. In patients with coronary artery disease without heart failure, the drug does not protect against major cardiovascular adverse events prompting questions about the ability of genetics to have predicted those effects. This study evaluates the effect of a variant in HCN4, ivabradine's drug target, on safety and efficacy endpoints. METHODS: We used genetic association testing and Mendelian randomization to predict the effect of ivabradine and heart rate lowering on cardiovascular outcomes. RESULTS: Using data from the UK Biobank and large GWAS consortia, we evaluated the effect of a heart rate-reducing genetic variant at the HCN4 locus encoding ivabradine's drug target. These genetic association analyses showed increases in risk for atrial fibrillation (OR 1.09, 95% CI: 1.06-1.13, P = 9.3 ×10-9) in the UK Biobank. In a cause-specific competing risk model to account for the increased risk of atrial fibrillation, the HCN4 variant reduced incident heart failure in participants that did not develop atrial fibrillation (HR 0.90, 95% CI: 0.83-0.98, P = 0.013). In contrast, the same heart rate reducing HCN4 variant did not prevent a composite endpoint of myocardial infarction or cardiovascular death (OR 0.99, 95% CI: 0.93-1.04, P = 0.61). CONCLUSION: Genetic modelling of ivabradine recapitulates its benefits in heart failure, promotion of atrial fibrillation, and neutral effect on myocardial infarction.

GenPipes: an open-source framework for distributed and scalable genomic analyses.

BACKGROUND: With the decreasing cost of sequencing and the rapid developments in genomics technologies and protocols, the need for validated bioinformatics software that enables efficient large-scale data processing is growing. FINDINGS: Here we present GenPipes, a flexible Python-based framework that facilitates the development and deployment of multi-step workflows optimized for high-performance computing clusters and the cloud. GenPipes already implements 12 validated and scalable pipelines for various genomics applications, including RNA sequencing, chromatin immunoprecipitation sequencing, DNA sequencing, methylation sequencing, Hi-C, capture Hi-C, metagenomics, and Pacific Biosciences long-read assembly. The software is available under a GPLv3 open source license and is continuously updated to follow recent advances in genomics and bioinformatics. The framework has already been configured on several servers, and a Docker image is also available to facilitate additional installations. CONCLUSIONS: GenPipes offers genomics researchers a simple method to analyze different types of data, customizable to their needs and resources, as well as the flexibility to create their own workflows.

Dirofilaria immitis JYD-34 isolate: whole genome analysis.

BACKGROUND: Macrocyclic lactone (ML) anthelmintics are used for chemoprophylaxis for heartworm infection in dogs and cats. Cases of dogs becoming infected with heartworms, despite apparent compliance to recommended chemoprophylaxis with approved preventives, has led to such cases being considered as suspected lack of efficacy (LOE). Recently, microfilariae collected from a small number of LOE isolates were used as a source of infection of new host dogs and confirmed to have reduced susceptibility to ML in controlled efficacy studies using L3 challenge in dogs. A specific Dirofilaria immitis laboratory isolate named JYD-34 has also been confirmed to have less than 100% susceptibility to ML-based preventives. For preventive claims against heartworm disease, evidence of 100% efficacy is required by FDA-CVM. It was therefore of interest to determine whether JYD-34 has a genetic profile similar to other documented LOE and confirmed reduced susceptibility isolates or has a genetic profile similar to known ML-susceptible isolates. METHODS: In this study, the 90Mbp whole genome of the JYD-34 strain was sequenced. This genome was compared using bioinformatics tools to pooled whole genomes of four well-characterized susceptible D. immitis populations, one susceptible Missouri laboratory isolate, as well as the pooled whole genomes of four LOE D. immitis populations. Fixation indexes (FST), which allow the genetic structure of each population (isolate) to be compared at the level of single nucleotide polymorphisms (SNP) across the genome, have been calculated. Forty-one previously reported SNP, that appeared to differentiate between susceptible and LOE and confirmed reduced susceptibility isolates, were also investigated in the JYD-34 isolate. RESULTS: The FST analysis, and the analysis of the 41 SNP that appeared to differentiate reduced susceptibility from fully susceptible isolates, confirmed that the JYD-34 isolate has a genome similar to previously investigated LOE isolates, and isolates confirmed to have reduced susceptibility, and to be dissimilar to the susceptible isolates. CONCLUSIONS: These results provide additional evidence for the link between genotype and the reduced susceptibility phenotype observed in such isolates as JYD-34. Further work on other isolates showing reduced susceptibility to ML is required to demonstrate the value of genetic analysis in predicting the response to ML chemoprophylaxis. The authors suggest that genetic analysis may be useful in helping to interpret the results of in vivo efficacy testing of ML heartworm preventives against D. immitis isolates.

OPINIONES SOBRE LAS PRÁCTICAS ANTICONCEPTIVAS EN ESTUDIANTES DE UNA FACULTAD DE HUMANIDADES EN SANTA MARTA / ATTITUDES ABOUT OPINIONS AND PRACTICES IN STUDENTS OF BIRTH CONTROL A FACULTY OF HUMANITIES IN SANTA MARTA

En el presente estudio se buscó determinar las opiniones sobre los métodos anticonceptivos y la relación existente entre la variable de estudio, el programa académico y el género en estudiantes de la facultad de humanidades de la Universidad del Magdalena. Mediante el cual se brindan datos actualizados sobre las conductas sexuales de riesgo de los estudiantes, los cuales pueden ser útiles para la prevención de esta problemática, por ello se realizó un estudio descriptivo-correlacional, utilizando un muestreo intencional, con una participación de 120 estudiantes. Los hallazgos permitieron concluir que los estudiantes plantean opiniones positivas y mayor uso sobre el preservativo y las píldoras; asimismo poseen opiniones negativas de la abstinencia, el dispositivo intrauterino y los implantes. Por otro lado, no se encontró relación entre el género y las opiniones sobre los métodos anticonceptivos, igualmente la opinión de los estudiantes no difiere según el programa.

In the present study views on contraception and the relationship between the variable gender study and students of the faculty of humanities at the University of Magdalena are determined. This article would provide data on sexual risk behaviors of students, which can be useful for the prevention of this problem, thus a descriptive correlational study was conducted using purposive sampling, with a participation of 120 students. The findings support the conclusion that students pose positive reviews and increased use of condoms and pills also have negative opinions of abstinence, intrauterine devices and implants. On the other hand, there is no relationship between gender and views on contraception, also the opinion of students does not differ according to the program.

Accion de los cambios hormonales sobre la funcion plaquetaria en nativos de la altura / Hormonal changes and platelets function in natives of high altitude

El objetivo de nuestro trabajo sobre las hormonas sexuales y estrogenos, tiene por finalidad, ver que cambios producen en la funcion plaquetaria, tanto en su parte cualitativa como cuantitativa, yaque se observa con mucha frecuencia de hematomas, fragilidad capilar (Petequias). En el sexo femenino, por lo que estudiamos a 50 mujeres en la que se tomo sangre pre y post menstruacion, en edades comprendidas entre 18 y 30 años comparando con mujeres menopausicas y varones de las mismas edades. En todos los casos se realizo una ficha clinica. Los parametros estudiados fueron la prueba de Rumpell-Lee, la agregacion plaquetaria con inductores tales como el ADP a diferente concentracion, colageno y ademas la relacion genetica con la determinacion de grupos sanguineos. Los resuktados nos demuestran una fragilidad capilar aumentada despues del ciclo: 15 petequias, a 20 cmHg (Normal 2-6; p 0.05), el conteo plaquetario en P.R.P. esta bajo < 300.000X mm3 y, mujeres menopausicas que no tienen los asiclos hormonales ovaricos; la agregacion con A.D.P. a 2,5 uM final es de 50 por ciento (p=0.05) antes, y 40 por ciento despues. Estos demuestran primeramente la hipoagregacion del nativo de altura y la accion hirmonal por la que observamos la presencia de hematomas y fragilidad capilar. En cuanto al grupo sanguineo, en nuestro muestreo los grupos sanguineos O, es de 60 por ciento de agregacion; el rupo A, un 47 por ciento tanto en grupo B y AB, un 35 por ciento . Con estos datos concluimos que la accion genetica muestra que es mas baja la agregacion en los grupos a-b-ab. Finalmente, los valores hormonales en nuestro medio dados por el Instituto de Medicina Nuclear es: para Estadiol=30 pg/ml y Progesterona=30ng/ml.