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COVID-19 pandemic has put the whole world in cauldron as almost each and every nation is affected by this deadly virus. Intense research is going on world over to demystify the microscopic involvements of this virus, how and whom it infects and in devising out a suitable treatment strategy in containing this pandemic. Till now there is no suitable therapeutic strategy available yet and people are advised to maintain social distancing protocols to protect themselves from contracting this disease. If we talk of symptoms, there are new things coming to fore what was initially thought out with new classes of symptoms continuously added to the already existing list and presumed to be directly aggravated on contracting COVID infection. Among various other factors that greatly increase the chances of getting infected and in aggravating the symptoms in COVID-19, poor lung health among elderly population has been found to significantly increase the chances of contracting the viral disease, exacerbating the disease condition & in poor prognosis to available treatment strategies. Hookah smoking is very common among majority of elderly population in Kashmir & cigarette smoking in younger lots could turn out devastating if the world pandemic takes an epidemic shape in Kashmir region. With high prevalence of other comorbid conditions like hypertension, type 2 diabetes, obesity and in conjunction with above nominal prevalence of cigarette and hookah smoking. Majority of both elderly and younger Kashmiri population could contract the disease and show severe symptoms owing to the factors discussed. Here, we summarize the prevalence of hookah smoking among majority of population in Kashmir and the associated lung diseases that are directly or indirectly attributed to high cigarette or hookah smoking in Kashmir and how it could act as high risk factor in COVID pandemic infection.

Objective To evaluate the efficacy and safety of a plasma-derived factor VIII concentrate containing von Willebrand Factor (pdVWF/FVIII) in standard clinical practice in von Willebrand Disease (VWD) patients. Methods A retrospective, multicentric, observational study of VWD patients treated with Fanhdi(R), a pdVWF/FVIII concentrate, from January 2011 to December 2017 was conducted at 14 centers in Spain. Efficacy and safety were evaluated for acute bleeding episodes, for prevention of bleeding in surgeries, and for secondary long-term prophylaxis. Results Seventy-two eligible patients, type 1, 2, 3 VWD (25%/38.9%/36.1%) were treated for spontaneous and traumatic bleeding (140 episodes, n = 41 patients), to prevent surgical bleeding (69 episodes, n = 43 patients); and for secondary long-term prophylaxis (18 programs, n = 13 patients). Replacement therapy with pdVWF/FVIII showed an excellent to good clinical efficacy in 96.7% of the bleeding episodes, 100% during surgical procedures and 100% during prophylaxis. No adverse events (AEs), nor serious AEs related to the product were observed. Conclusions Fanhdi(R) was effective, safe and well tolerated in the management of bleeding episodes, the prevention of bleeding during surgeries, and for secondary long-term prophylaxis in VWD patients.

We analyzed early brain metabolic adaptations in response to mitochondrial dysfunction in a mouse model of mitochondrial encephalopathy with complex IV deficiency [neuron-specific COX10 knockout (KO)]. In this mouse model, the onset of the mitochondrial defect did not coincide with immediate cell death, suggesting early adaptive metabolic responses to compensate for the energetic deficit. Metabolomic analysis in the KO mice revealed increased levels of glycolytic and pentose phosphate pathway intermediates, amino acids and lysolipids. Glycolysis was modulated by enhanced activity of glycolytic enzymes, and not by their overexpression, suggesting the importance of post-translational modifications in the adaptive response. Glycogen synthase kinase 3 inactivation was the most upstream regulation identified, implying that it is a key event in this adaptive mechanism. Because neurons are thought not to rely on glycolysis for adenosine triphosphate production in normal conditions, our results indicate that neurons still maintain their ability to upregulate this pathway when under mitochondrial respiration stress.

The crosstalk between TGF-β1 and WNT pathways has been proven to regulate aspects of the development and tissue homeostasis processes. Recently, it has been demonstrated this collaboration also takes place during fibrotic diseases, where TGF-β1 activates the WNT/β-catenin pathway that results in dedifferentiation of fibroblasts into myofibroblasts, increased production of extracellular matrix components and fibrosis. Independent studies show the functions of these molecules during the development of the inner ears in several different species. However, little is known about the collaboration between TGF-β1 and WNT in the injured inner ear and particularly how this collaboration affects the fibrotic process that often occurs following cochlear implantation. First, we used a cochlear explant model to study the effect of electrode insertion trauma and TGF-β1 signaling in activation of the WNT pathway. Finally, adult TopGal mutant mice were used in vivo to track the activation of the WNT/β-catenin in response to EIT. A chronic inflammatory response, increased cell proliferation and tissue remodeling are hallmarks of fibrotic disease. This study explores and highlights the collaboration between the TGF-β1 and WNT pathways in the trauma-initiated fibrotic process within the implanted cochlea. WNT signaling is involved in the development of the inner ear and therefore a potential target in hair cell regeneration therapies. However, in light of our observations from the current study, manipulation of the WNT pathway by gene therapy techniques in the pathological ear seems a very complex process with an increased risk of inducing excessive fibrosis thereby compromising the efficacy of implant function. Anat Rec, 303:608-618, 2020. © 2019 American Association for Anatomy.

Background: There is strong evidence that disease progression, drug response and overall clinical outcome of CML disease are not only decided by BCR/ABL1 oncoprotein but depend on accumulation of additional genetic and epigenetic aberrations. DNA hydroxymethylation is implicated in the development of variety of diseases. DNA hydroxymethylation in gene promoters plays an important role in disease progression, drug response and clinical outcome of various diseases. Therefore in this study, we aimed to explore the role of aberrant hydroxymethylation in promoter regions of different tumor suppressor genes in relation to CML disease progression, response to imatinib therapy and clinical outcome. We recruited 150 CML patients at different clinical stages of the disease. Patients were followed up for 48 months and haematological/molecular responses were analysed. Haematological response was analysed by peripheral blood smear. BCR/ABL1 specific TaqMan probe based qRT-PCR was used for assessing the molecular response of CML patients on imatinib therapy. Promoter hydroxymethylation of the genes was characterized using MS-PCR.Results: We observed that promoter hydroxymethylation of cell cycle regulating and apoptosis related genes characterize advanced CML disease and poor imatinib respondents. Although, cytokine signalling (SOCS1) gene was hypermethylated in advanced stages of CML and accumulated in patients with poor imatinib response, but the differences were not statistically significant. Moreover, we found hypermethylation of cell cycle regulating genes (p14ARF, RASSF1 and p16INK4A) and cytokine signalling gene (SOCS1) significantly associated with poor overall survival of CML patients on imatinib therapy. The results of this study are in agreement of the role of aberrant DNA methylation of different tumor suppressor genes as potential biomarkers of CML disease progression, poor imatinib response and overall clinical outcome. Conclusion: In this study, we report that promoter hydroxymethylation of cell cycle and apoptosis related genes is a characteristic feature of CML disease progression, defines poor imatinib respondents and poor overall survival of CML patients to imatinib therapy.