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Holloway Just posted an update 3 months, 2 weeks ago
Seasonal trends in tuberculosis (TB) notifications have been observed in several countries but are poorly understood. Explanatory factors may include weather, indoor crowding, seasonal respiratory infections and migration. Using enhanced citywide TB surveillance data collected over nine years in Blantyre, Malawi, we set out to investigate how weather and seasonality affect temporal trends in TB case notification rates (CNRs) across different demographic groups. We used data from prospective enhanced surveillance between April 2011 and December 2018, which systematically collected age, HIV status, sex and case notification dates for all registering TB cases in Blantyre. We retrieved temperature and rainfall data from the Global Surface Summary of the Day weather station database. We calculated weekly trends in TB CNRs, rainfall and temperature, and calculated 10-week moving averages. To investigate the associations between rainfall, temperature and TB CNRs, we fitted generalized linear models using a distributr, by limited healthcare access, by patterns of seasonal respiratory infections precipitating cough and care-seeking, or by migratory patterns related to planting and harvesting during the rainy season.Epstein-Barr virus (EBV) is one of the most common viruses latently infecting humans. find more Little is known about the impact of human genetic variation on the large inter-individual differences observed in response to EBV infection. To search for a potential imprint of host genomic variation on the EBV sequence, we jointly analyzed paired viral and human genomic data from 268 HIV-coinfected individuals with CD4 + T cell count less then 200/mm3 and elevated EBV viremia. We hypothesized that the reactivated virus circulating in these patients could carry sequence variants acquired during primary EBV infection, thereby providing a snapshot of early adaptation to the pressure exerted on EBV by the individual immune response. We searched for associations between host and pathogen genetic variants, taking into account human and EBV population structure. Our analyses revealed significant associations between human and EBV sequence variation. Three polymorphic regions in the human genome were found to be associated with EBV variation one at the amino acid level (BRLF1p.Lys316Glu); and two at the gene level (burden testing of rare variants in BALF5 and BBRF1). Our findings confirm that jointly analyzing host and pathogen genomes can identify sites of genomic interactions, which could help dissect pathogenic mechanisms and suggest new therapeutic avenues.Mitochondrial dysfunction is an important factor of the aging process and may play a key role in various diseases. Mitochondrial DNA copy number (mtDNA-CN) is an indirect measure of mitochondrial dysfunction and is associated with type 2 diabetes mellitus (T2DM); however, whether mtDNA-CN can predict the risk of developing T2DM is not well-known. We quantified absolute mtDNA-CN in both prevalent and incident T2DM by well-optimized droplet digital PCR (ddPCR) method in a population-based follow-up study of middle aged (50-59 years) Swedish women (n = 2387). The median follow-up period was 17 years. Compared to those who were free of T2DM, mtDNA-CN was significantly lower in both prevalent T2DM and in women who developed T2DM during the follow-up period. Mitochondrial DNA-copy number was also associated with glucose intolerance, systolic blood pressure, smoking status and education. In multivariable Cox regression analysis, lower baseline mtDNA-CN was prospectively associated with a higher risk of T2DM, independent of age, BMI, education, smoking status and physical activity. Moreover, interaction term analysis showed that smoking increased the effect of low mtDNA-CN at baseline on the risk of incident T2DM. Mitochondrial DNA-copy number may be a risk factor of T2DM in women. The clinical usefulness of mtDNA-CN to predict the future risk of T2DM warrants further investigation.Genetic factors are one of the most important causes of non-obstructive azoospermia (NOA). ESX1 is an X-linked testis-biased expressed gene, and a potential biomarker for testicular sperm retrieval in NOA patients, yet few systematic studies have investigated its association with NOA. Here, we performed selected exonic sequencing in a large cohort of Chinese males, and four novel missense mutations (including one compound mutation), one novel synonymous mutation of ESX1 unique to NOA patients were identified. We analyzed the effects of ESX1 mutations on cyclin A degradation and cell cycle progression by immunoprecipitation assay and flow cytometry, and found that the compound mutant p.[P365R; L366V] ESX1 compromised the stabilizing effect of ESX1 on polyubiquitinated cyclin A, thereby causing the failure of M phase arrest in cells. Further studies showed that the deleterious effect of the compound mutations on ESX1 protein function was attributed to p.P365R but not p.L366V alteration. The novel ESX1 mutation p.P365R might confer high risk for NOA in Han Chinese population, probably via affecting cell cycle control.We non-invasively evaluated macular non-perfused areas (m-NPAs) of branch retinal vein occlusion (BRVO) using optical coherence tomography (OCT) angiography and the Humphrey visual field analyser 10-2 programme (HFA 10-2). We enrolled 30 patients (30 eyes) with macular oedema secondary to BRVO. OCT angiography was used to photograph the macula at 6 × 6-mm; sizes of m-NPAs in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were measured in four areas. For HFA 10-2, we divided the actual measurement threshold of 68 points into four areas and calculated the mean central visual field sensitivity (CVFS). The correlation between the mean m-NPA and mean CVFS (dB) in each area was examined. There was a strong correlation between the m-NPA of each region detected in SCP and DCP, and the mean CVFS of each corresponding area (SCP r = - 0.83, r = - 0.64, r = - 0.73, and r = - 0.79; DCP r = - 0.82, r = - 0.71, r = - 0.71, and r = - 0.70), p values were less then 0.001 for all. m-NPAs were associated with decreased visual field sensitivity in BRVO.