Gene-Gene and Gene-Environmental Interactions of Childhood Asthma: A Multifactor Dimension Reduction Approach

Background: The importance of gene-gene and gene-environment interactions on asthma is well documented in literature, but a systematic analysis on the interaction between various genetic and environmental factors is still lacking. Methodology/Principal Findings: We conducted a population-based, case-control study comprised of seventh-grade children from 14 Taiwanese communities. A total of 235 asthmatic cases and 1,310 non-asthmatic controls were selected for DNA collection and genotyping. We examined the gene-gene and gene-environment interactions between 17 singlenucleotide polymorphisms in antioxidative, inflammatory and obesity-related genes, and childhood asthma. Environmental exposures and disease status were obtained from parental questionnaires. The model-free and non-parametrical multifactor dimensionality reduction (MDR) method was used for the analysis. A three-way gene-gene interaction was elucidated between the gene coding glutathione S-transferase P (GSTP1), the gene coding interleukin-4 receptor alpha chain (IL4Ra) and the gene coding insulin induced gene 2 (INSIG2) on the risk of lifetime asthma. The testing-balanced accuracy on asthma was 57.83 % with a cross-validation consistency of 10 out of 10. The interaction of preterm birth and indoor dampness had the highest training-balanced accuracy at 59.09%. Indoor dampness also interacted with many genes, including IL13, beta-2 adrenergic receptor (ADRB2), signal transducer and activator of transcription 6 (STAT6). We also used likelihood ratio tests for interaction and chi-square tests to validate our results and all tests showed statistical significance

Life-threatening heart failure in meningococcal septic shock in children: non-invasive measurement of cardiac parameters is of important prognostic value

Heart failure is a life-threatening complication of fulminant meningococcal septic shock (MSS). Depression of left ventricular function, in particular, is thought to be due to circulating meningococcal endotoxin. Myocardial failure leads to ventricular dilation expressed by an increased left-ventricle end-diastolic diameter (LVED). With ultrasonography, LVED can be accurately measured as well as the shortening fraction (SF). In an evaluative study we investigated the accuracy of the SF and compared it to the accuracy of the Glasgow meningococcal septicemia prognostic score (GMSPS) in the prediction of mortality in children with fulminant MSS. In 27 children admitted in a 4-year period with a presumptive clinical diagnosis of fulminant MSS, hypotension persisted for more than 1 h despite volume loading and inotropic therapy. Seven of these children died (26%); all had an SF or =10 (the sensitivity of both scores was 100%). Positive predictive values of the SF and GMSPS were 41% and 58% respectively. CONCLUSIONS: SF can be used in addition to other severity scores in clinical decision-making and contribute to the selection of children with the worst prospects for inclusion in experimental treatment studie

The outcome of pulmonary hypertension and its association with pulmonary artery dilatation

Background: Pulmonary artery (PA) dilatation is often seen in pulmonary hypertension (PH) and is considered a long-term consequence of elevated pressure. The PA dilates over time and therefore may reflect disease severity and duration. Survival is related to the stage of the disease at the time of diagnosis and therefore PA diameter might be used to predict prognosis. This study evaluates the outcome of patients with pulmonary arterial hypertension (PAH) and chronic thrombo-embolic pulmonary hypertension (CTEPH) and investigates whether PA diameter at the time of diagnosis is associated with mortality. Methods: Patients visiting an outpatient clinic of a tertiary centre between 2004 and 2018 with a cardiac catheterisation confirmed diagnosis of PAH or CTEPH and a CT scan available for PA diameter measurement were included. PA diameter and established predictors of survival were collected (New York Heart Association (NYHA) class, N‑terminal pro-brain natriuretic peptide (NT-proBNP) level and 6‑min walking distance (6MWD)). Results: In total 217 patients were included (69% female, 71% NYHA class ≥III). During a median follow-up of 50 (22–92) months, 54% of the patients died. Overall survival was 87% at 1 year, 70% at 3 years and 58% at 5 years. The mean PA diameter was 34.2 ± 6.2 mm and was not significantly different among all the diagnosis groups. We found a weak correlation between PA diameter and mean PA pressure (r = 0.23, p < 0.001). Male sex, higher age, shorter 6MWD and higher NT-proBNP level were independently associated with mortality, but PA diameter was not. Conclusion: The prognosis of PAH and CTEPH is still poor. Known predictors of survival were confirmed, but PA diameter at diagnosis was not associated with survival in PAH or CTEPH patients

Presence of Genetic Variants Among Young Men With Severe COVID-19

Contains fulltext : 222168.pdf (Publisher’s version ) (Closed access