Almost every age group is at higher risk for serious flu complications. The major problem arising these days regarding the control of influenza disease is the development of resistance among the influenza viruses against the existing anti-viral drugs that are being recommended. Also, these antiviral drugs have a number of side effects. The main objective of the present paper is to explore riboswitches as a novel target for design of drugs for influenza virus in order to address the issues of resistance and side effects of present drugs. Riboswitches are present in the non-coding region of mRNA that sense changes in the cellular environment and directly mediate appropriate gene control responses. These riboswitches are primarily found in the 5' untranslated regions of messenger RNAs. In the present paper in-silico approach is proposed for the prediction of riboswitches for the strains of influenza virus, their binding sites and design of their inhibitors. Two riboswitches have been predicted for the three strains of influenza virus and five inhibitors have been identified for each of the two riboswitches by virtual screening. These inhibitors are found to be free from the side effects of antiviral agents and have remote chances of being resistant.
Intensification in the frequency of diabetes and the associated vascular complications has been a root cause of blindness and visual impairment worldwide. One such vascular complication which has been the prominent cause of blindness; retinal vasculature, neuronal and glial abnormalities is diabetic retinopathy (DR), a chronic complicated outcome of Type 1 and Type 2 diabetes. It has also become clear that “genetic” variations in population alone can’t explain the development and progression of diabetes and its complications including DR. DR experiences engagement of foremost mediators of diabetes such as hyperglycemia, oxidant stress, and inflammatory factors that lead to the dysregulation of “epigenetic” mechanisms involving histone acetylation and histone and DNA methylation, chromatin remodeling and expression of a complex set of stress-regulated and disease-associated genes. In addition, both elevated glucose concentration and insulin resistance leave a robust effect on epigenetic reprogramming of the endothelial cells too, since endothelium associated with the eye aids in maintaining the vascular homeostasis. Furthermore, several studies conducted on the disease suggest that the modifications of the epigenome might be the fundamental mechanism(s) for the proposed metabolic memory’ resulting into prolonged gene expression for inflammation and cellular dysfunction even after attaining the glycemic control in diabetics. Henceforth, the present review focuses on the aspects of genetic and epigenetic alterations in genes such as vascular endothelial growth factor and aldose reductase considered being associated with DR. In addition, we discuss briefly the role of the thioredoxin-interacting protein TXNIP, which is strongly induced by high glucose and diabetes, in cellular oxidative stress and mitochondrial dysfunction potentially leading to chromatin remodeling and ocular complications of diabetes. The identification of disease-associated genes and their epigenetic regulations will lead to potential new drugs and gene therapies as well as personalized medicine to prevent or slow down the progression of DR.
A 9-year-old girl who presented with dyspnea on exertion was diagnosed with total anomalous systemic venous connection to the left atrium (both venae cavae), no left superior vena cava, and a moderate-sized atrial septal defect with severe pulmonary arterial hypertension and ectopic atrial rhythm. She underwent septation of the common atrium using autologous pericardium, thereby rerouting the superior vena cava, inferior vena cava, and coronary sinus to the right atrium. Her postoperative course was uneventful. This case is reported for its rarity of presentation with severe pulmonary arterial hypertension and ectopic atrial rhythm.
Stenting of the arterial duct (PDA) has become a standard palliation for ductal-dependent pulmonary circulation. Carotid arterial access provides a direct route for stenting vertical ducts. We evaluated our early results of hybrid ductal stenting via surgical carotid cutdown. Methods and results: In this retrospective single centre cohort study, hybrid PDA stenting was attempted in 11 patients with “flip technique”, between January 2020 and February 2021, and was successful in 10. Median age was 29 days (interquartile range 17.5–87) and mean weight 3.37 ± 1.23 kg. Mean fluoroscopy time was 13.58 ± 5.35 minutes, mean procedure time was 48.50 ± 22.5 minutes, and mean radiation dose was 1719.5 ± 1217.6 mGycm2. Mean time for cutdown was 9.9 ± 2.4 minutes and for haemostasis and suturing was 25.3 ± 11.0 minutes. Median duration of ventilation post-stenting was 26 hours (interquartile range 21–43.75). The median ICU stay post-procedure was 5 days (interquartile range 4–7.25) and mean hospital stay was 12 ± 6.3 days. On early follow-up, carotid patency was confirmed in all patients with colour Doppler, with no intravascular thrombi, narrowing, haematomas, or aneurysms noted. There were no complications secondary to vascular access. There was one early mortality, 27 days post-stenting, which was unrelated to the procedure. Conclusion: This study adds to the limited literature on ductal stenting with carotid access and the flip technique. In our early experience, the hybrid carotid approach is an attractive alternative to percutaneous carotid puncture and has simplified a complex and challenging intervention, with good outcomes.
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