It is increasingly recognized that microbes that reside in and on human body sites play major roles in modifying the pathogenesis of several diseases including cancer. However, specific microbes or microbial communities that can be mechanistically linked to cervical carcinogenesis remain largely unexplored. The purpose of the study was to examine the association between cervical microbiota and high-grade cervical intraepithelial neoplasia (CIN 2+) in women infected with high-risk (HR) human papillomaviruses (HPVs) and to assess whether the cervical microbiota are associated with oxidative DNA damage as indicated by the presence of cervical cells positive for 8-hydroxy-2′-deoxyguanosine. Study included 340 women diagnosed with CIN 2+ (cases) and 90 diagnosed with CIN 1 (non-cases). Microbiota composition was determined by Illumina sequencing of the 16S rRNA gene amplified from DNA extracted from cervical mucus samples. Measures of alpha/beta-diversity were not associated with either CIN severity or oxidative DNA damage. However, a cervical mucosal community type (CT) dominated by L. iners and unclassified Lactobacillus spp. was associated with CIN 2+ (OR=3.48, 95% CI: 1.27–9.55). Sequence reads mapping to Lactobacillaceae, Lactobacillus, L. reuteri and several sub-genus level Lactobacillus OTUs were also associated with CIN 2+ when examined independently (effect size >2.0; p < 0.05). Our 16S rRNA sequencing results need confirmation in independent studies using whole-genome shotgun sequencing and that would allow sharpening the suggested associations at finer taxonomic levels. Our results provide little evidence that DNA oxidative damage mediates the effect of the microbiome on the natural history of HPV infection and CIN severity.
Introduction: The novel coronavirus pandemic has caused significant mortality throughout the world. This study was done as there is scarce data on mortality predictors in severe COVID-19 pneumonia patients admitted to ICU in the Indian population. Material and methods: A retrospective study was conducted on COVID-19 pneumonia patients admitted to tertiary care center during June–October 2020. The records of patients admitted to ICU were collected and data included demography, symptoms, comorbidites and vital parameters. Laboratory parameters included complete hemogram, random blood sugar, S.Ferritin, S.LDH, renal function test, liver function test. Treatment-associated information such as the use of remdesivir, timing of initiating rem-desivir after the symptom onset, the use of steroids, use of anticoagulants, use of HFNC, NIV, ventilator were collected. 30 days mortality data post-discharge was collected via telephonic interview. Results: 4,012 confirmed cases of COVID-19 were admitted to hospital, of which 560 (13.95%) with severe pneumonia were included in the study. Mean age was 57.75 ± 13.96 years. The mortality rates were 54.64% among severe COVID-19 cases and 5% among mild to moderate COVID-19 cases. The Cox multinominal regression analysis identified SpO2/FiO2 < 400, age > 50 years, duration of symptom > 4 days, serum ferritin > 450 µg/L, respiratory rate > 23/min, the presence of comorbidities and non-usage of remdesivir were independently associated with increased mortality. Mortality rate at 30 days was 56.60%. Conclusion: Severe COVID-19 pneumonia is associated with very high mortality, especially in a resource-constrained setting. The use of remdesivir may have to be considered early in the course of disease to prevent excess mortality related to COVID-19.
Retinoblastoma is a rare pediatric tumor of the retina, caused by the homozygous loss of the Retinoblastoma 1 (RB1) tumor suppressor gene. Previous microarray studies have identified changes in the expression profiles of coding genes; however, our understanding of how non-coding genes change in this tumor is absent. This is an important area of research, as in many adult malignancies, non-coding genes including LNC-RNAs are used as biomarkers to predict outcome and/or relapse. To establish a complete and in-depth RNA profile, of both coding and non-coding genes, in Retinoblastoma tumors, we conducted RNA-seq from a cohort of tumors and normal retina controls. This analysis identified widespread transcriptional changes in the levels of both coding and non-coding genes. Unexpectedly, we also found rare RNA fusion products resulting from genomic alterations, specific to Retinoblastoma tumor samples. We then determined whether these gene expression changes, of both coding and non-coding genes, were also found in a completely independent Retinoblastoma cohort. Using our dataset, we then profiled the potential effects of deregulated LNC-RNAs on the expression of neighboring genes, the entire genome, and on mRNAs that contain a putative area of homology. This analysis showed that most deregulated LNC-RNAs do not act locally to change the transcriptional environment, but potentially function to modulate genes at distant sites. From this analysis, we selected a strongly down-regulated LNC-RNA in Retinoblastoma, DRAIC, and found that restoring DRAIC RNA levels significantly slowed the growth of the Y79 Retinoblastoma cell line. Collectively, our work has generated the first non-coding RNA profile of Retinoblastoma tumors and has found that these tumors show widespread transcriptional deregulation.
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