Search

Roles for the baculoviral inhibitor of apoptosis repeat-containing (BIRC) genes, BIRC2 and BIRC3, may include signaling to the inflammatory transcription factor, nuclear factor-κB (NF-κB) and protection from cell death. However, distinct functions for each BIRC are not well-delineated. Given roles for the epithelium in barrier function and host defence, BIRC2 and BIRC3 expression was characterized in pulmonary epithelial cell lines and primary human bronchial epithelial cells (pHBECs) grown as undifferentiated cells in submersion culture (SC) or as highly differentiated cells at air-liquid interface (ALI). In A549 cells, interleukin-1β (IL1B) and tumor necrosis factor α (TNF) induced BIRC3 mRNA (~20-50-fold), with maximal protein expression from 6–24 h. Similar effects occurred in BEAS-2B and Calu-3 cells, as well as SC and ALI pHBECs. BIRC2 protein was readily detected in unstimulated cells, but was not markedly modulated by IL1B or TNF. Glucocorticoids (dexamethasone, budesonide) modestly increased BIRC3 mRNA and protein, but showed little effect on BIRC2 expression. In A549 cells, BIRC3 mRNA induced by IL1B was unchanged by glucocorticoids and showed supra-additivity with TNF-plus-glucocorticoid. Supra-additivity was also evident for IL1B-plus-budesonide induced-BIRC3 in SC and ALI pHBECs. Using A549 cells, IL1B- and TNF-induced BIRC3 expression, and to a lesser extent, BIRC2, was prevented by NF-κB inhibition. Glucocorticoid-induced BIRC3 expression was prevented by silencing and antagonism of the glucocorticoid receptor. Whereas TNF, but not IL1B, induced degradation of basal BIRC2 and BIRC3 protein, IL1B- and TNF-induced BIRC3 protein remained stable. Differential regulation by cytokines and glucocorticoids shows BIRC2 protein expression to be consistent with roles in rapid signaling events, whereas cytokine-induced BIRC3 may be more important in later effects. While TNF-induced degradation of both BIRCs may restrict their activity, cytokine-enhanced BIRC3 expression could prime for its function. Finally, shielding from glucocorticoid repression, or further enhancement by glucocorticoid, may indicate a key protective role for BIRC3. [ABSTRACT FROM AUTHOR]

Background: Lack of awareness about viral hepatitis (VH) potentially predisposes the healthcare workers (HCWs) to a higher risk of infection and may in turn increase the risk of transmission of the infection to their families and in the community. Thus, combating VH, requires adequate and updated training to the HCWs. With this objective, Project PRAKASH designed a meticulously planned training program, aimed to assess the effect of a one-day training on VH among in-service nurses. Methods and material: The content and schedule of scientific sessions of the training program were decided by subject experts to improve knowledge, attitude and practice(KAP) related to VH among in-service nurses. A 54-item questionnaire divided into four domains: Transmission and Risk Factors; Prevention; Treatment; Pathophysiology and Disease Progression were used to assess the KAP related to VH. The questionnaire consisted of four sections: demographic details, knowledge(30-items), attitude(12-items) and practice(12-itmes) with a total score of 30, 60 and 24 respectively in each section. The pre-post knowledge assessment was done and impact assessment survey was undertaken among the participants who completed six months post-training period. Paired-t-test was used to assess the effect of training on knowledge using SPSSv-22. Results: A total of 5253 HCWs were trained through 32 one-day trainings, however data for 4474 HCWs was included in final pre-post knowledge analysis after removing the missing/incomplete data. Mean age of participants was 33.7±8.4 with median experience of 8(IQR: 3–13). Mean improvement in knowledge score was found to be significant (p<0.001) with mean knowledge score of 19.3±4.4 in pre-test and 25.7±3.9 in the post-test out of 30. Impact assessment survey suggested change in attitude and practice of HCWs. Conclusion: The one-day training programs helped the in-service nurses to enhance their knowledge related to viral hepatitis. The study provided a roadmap to combating viral hepatitis through health education among HCWs about viral hepatitis. [ABSTRACT FROM AUTHOR]

There are very few reports that describe the mutational landscape of cervical cancer, one of the leading cancers in Indian women. The aim of the present study was to investigate the somatic mutations that occur in cervical cancer. Whole exome sequencing of 10 treatment naïve tumour biopsies with matched blood samples, from a cohort of Indian patients with locally advanced disease, was performed. The data revealed missense mutations across 1282 genes, out of 1831 genes harbouring somatic mutations. These missense mutations (nonsynonymous + stop-gained) when compared with pre-existing mutations in the COSMIC database showed that 272 mutations in 250 genes were already reported although from cancers other than cervical cancer. More than 1000 novel somatic variations were obtained in matched tumour samples. Pathways / genes that are frequently mutated in various other cancers were found to be mutated in cervical cancers. A significant enrichment of somatic mutations in the MAPK pathway was observed, some of which could be potentially targetable. This is the first report of whole exome sequencing of well annotated cervical cancer samples from Indian women and helps identify trends in mutation profiles that are found in an Indian cohort of cervical cancer. [ABSTRACT FROM AUTHOR]