Anomalous origin of the circumflex coronary artery from the right sinus of Valsalva is the most common coronary anomaly and is usually considered benign. Although several researchers in the past believed that aberrancy predisposes this vessel to accelerated atherosclerosis, this could not get wide acceptance owing to lack of convincing data. To examine the suggestion that atherosclerosis affects the anomalous circumflex artery more severely, the authors reviewed the clinical and angiographic features of patients with this anomaly identified from 2,684 coronary angiography procedures performed between January 1998 and March 2000 at their institution. The degree of atherosclerotic narrowing in the anomalous artery was compared with that in other coronary arteries in the same patient as well as in the nonanomalous circumflex arteries in controls. For comparison 3 control subjects were selected for each patient with anomalous circumflex artery, matched by age, sex, and clinical presentations. The results showed earlier and greater degree of atherosclerotic narrowing of the anomalous artery as compared to the other coronary arteries in the same patients as well as to nonanomalous circumflex arteries of age- and gender-matched control subjects with similar clinical characteristics. However, this predilection for atherosclerosis was evident only in anomalous vessels arising from the right side and pursuing a retroaortic course. The anomalous artery was responsible for myocardial infarction in 3 patients, all of whom were 60 years or older. Two of the patients with this anomaly and myocardial infarction underwent successful angioplasty with stent placement for symptomatic relief.
Administration of oral azithromycin, in addition to previously well-tolerated long-term amiodarone therapy, was associated with a marked prolongation of QT interval and increased QT dispersion, both substrates for life-threatening ventricular tachyarrhythmia and torsades de pointes. This is a report of QT prolongation and increased QT dispersion associated with the use of azithromycin. The report assumes an added significance, in view of widespread empirical use of this antibiotic for the treatment of lower respiratory infections and belief of its safety in patients with cardiac diseases. Based on the authors' experience, they would like to emphasize that the combination of azithromycin with other drugs known to prolong QT or causing torsades de pointes be used with caution until the question of the proarrhythmic effect of azithromycin is resolved by further studies.
Purpose Cervical cancer is one of the leading cancers among women in India. Its prevention and control require a concerted effort to improve awareness among women regarding primary and secondary prevention strategies as well as access to care for treatment and palliation. A focused strategy is important to reach the World Health Organization’s targets for cervical cancer elimination, due to be completed by 2030. Methods Currently available literature was reviewed regarding cervical cancer prevention strategies in India including various national programmes and other initiatives on the part of government, non-governmental organizations and professional organizations. Their applicability to the present situation was assessed. Results National programmes need to build on success stories of various states and neighbouring countries as well as to audit the performance. Strengthening of cancer registries and improvement of linkages between different healthcare levels with incorporation of task-shifting, adding digital technology and supporting programmes that promote women’s welfare and health will also provide synergy to cancer control programmes. In the current pandemic era, HPV self-sampling can be an ideal method for screening. The development of an affordable, point-of-care HPV test is urgently needed to facilitate its introduction in low- and middle-income countries. HPV vaccination efforts need to be speeded up. Conclusion Scaling up of cervical cancer prevention with inclusion of widespread HPV vaccination and primary HPV test should be the new standard of care.
The unanticipated outbreak of Coronavirus had proven detrimental to human existence. It had created waves of panic, anxiety, and fear among people hence facilitating stigmatization toward an infected person. This stigmatization further influences patients health-seeking behaviour due to the trust deficit in the public health system. The virus had placed the world in an impotent situation as people helplessly watched their loved ones pass away in the absence of effective treatment. Dead bodies are denied a dignified death due to mandatory guidelines prescribed by countries to control the pandemic. This article attempts to understand the process of stigmatization of Coronavirus and its mechanism of influencing the health-seeking behaviour of people. Moreover, the way this stigmatization, accompanied by fear and anxiety, led to the denial of having a dignified death in India.
Classical Non-homologous End Joining (NHEJ) pathway is the mainstay of cellular response to DNA double strand breaks. While aberrant expression of genes involved in this pathway has been linked with genomic instability and drug resistance in several cancers, limited information is available about its clinical significance in colon cancer. We performed a comprehensive analysis of seven essential genes, including XRCC5, XRCC6, PRKDC, LIG4, XRCC4, NHEJ1, and PAXX of this pathway, in colon cancer using multi-omics datasets, and studied their associations with molecular and clinicopathological features, including age, gender, stage, KRAS mutation, BRAF mutation, microsatellite instability status and promoter DNA methylation in TCGA colon cancer dataset. This analysis revealed upregulation of XRCC5, PRKDC, and PAXX in colon cancer compared to normal colon tissues, while LIG4 and NHEJ1 (XLF) displayed downregulation. The expression of these genes was independent of age and KRAS status, while XRCC5, PRKDC, and LIG4 exhibited reduced expression in BRAF mutant tumors. Interestingly, we observed a strong association between XRCC6, XRCC5, PRKDC and LIG4 overexpression and microsatellite instability status of the tumors. In multivariate analysis, high PAXX expression emerged as an independent prognostic marker for poor overall and disease specific survival. We also observed hypomethylation of PAXX promoter in tumors, which exhibited a strong correlation with its overexpression. Furthermore, PAXX overexpression was also associated with several oncogenic pathways as well as a reduction in numbers of tumor-infiltrating lymphocytes.
Melanoma associated antigen (MAGE) is an extensively studied family of tumor-associated genes that share a common MAGE homology domain (MHD). Based upon their expression pattern, MAGE genes have been broadly classified into type 1 MAGEs (T1Ms) and type 2 MAGEs (T2Ms) categories. Interestingly, several T2Ms are highly expressed in the brain and involved in the regulation of neuronal development, differentiation, and survival. Available literature suggests possible tumor suppressor functions of a few T2Ms, while information available about their expression, regulation, and clinical significance in glioma is scanty. This prompted us to perform a comprehensive analysis of T2M expression in glioma. Gene expression data from glioma datasets: Oncomine, TCGA, and REMBRANDT study, were used to assess the mRNA expression of T2M genes (MAGED1, MAGED2, MAGED3, MAGED4, MAGED4B, MAGEE1, MAGEE2, MAGEF1, MAGEH1, MAGEL2, NSMCE3, and NDN), and their association with clinical characteristics and composition of the tumor microenvironment. Further, mutation, copy number alteration, and DNA methylation data from TCGA were assessed for determining potential mechanisms of T2Ms expression in glioma. Expression analysis revealed overexpression of MAGED subfamily genes in glioma, while other genes of this family exhibited reduced expression in advanced grades of this malignancy. Further, the expression of T2Ms exhibited varying extent of positive correlations with each other. Amongst downregulated T2Ms, MAGEH1 expression exhibited negative correlations with DNA methylation. Additionally, genes associated with MAGEH1 were enriched in Myc and Hedgehog signaling. Furthermore, T2Ms downregulation was associated with immune infiltration in glioma tissues and poor overall survival of glioma patients. In multivariate Cox regression analysis, MAGEH1 emerged as an independent prognosticator in lower grade glioma. Conclusively, these results suggest that expression of T2Ms is associated with important clinical and molecular features in glioma. Mechanistic studies may further provide novel insights into their role in glioma progression.
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