Chemo-metric assisted UV-spectrophotometric methods for simultaneous estimation of Darunavir ethanolate and Cobicistat in binary mixture and their tablet formulation.

Darunavir ethanolate (DRV) and Cobicistat (CBS) is a combination of antiretroviral drugs used for the treatment of human immunodeficiency virus (HIV) infections. Two Chemo-metric assisted UV-spectrophotometric methods were developed for simultaneous estimation of DRV and CBS in tablet dosage form, namely; partial least square (PLS) and Classical least square method (CLS). The proposed methods were successfully applied for simultaneous determination of DRV and CBS in a laboratory mixture and their tablet formulation to achieve maximum sensitivity and lowest error. The applied methods were validated as per ICH guidelines and found to be linear in the concentration range of 5-30µg/mL for DRV and 5-30µg/mL for CBS. The developed methods were statistically comared with reported UPLC method where no significant difference was found relating to both accuracy and precision. Thus, the proposed methods can be effectively utilized for the routine quality control assessment of these drugs in commercial tablet dosage form.

Biclonal gammopathay in a case of severe COVID-19.

COVID-19 is a disease caused by a coronavirus named as SARS-CoV-2. It has become pandemic due to its contagious nature. Majority of the patients are asymptomatic or having mild flu like symptoms. Few need hospitalisation due to severe acute respiratory infection (SARI). Co-morbidity like diabetes, hypertension, renal failure etc. are associated with severe COVID-19 that often causes death. There have been only two published case reports of monoclonal gammopathy of unknown significance (MGUS) in patients with COVID-19 disease. Cytokine storm is often observed in severe COVID-19 and various cytokines including IL-6 that activates plasma cells are increased in blood in this condition. Here we present a case of severe COVID-19 patient with bioclonal gammopathy. He was known diabetic and hypertensive on treatment. He developed SARI, cytokines storm and septicaemia, treated with antibiotics, enoxaparin, hydroxychloroquine, insulin, anti-hypertensives, put on ventilator, subsequently developed septicaemia, multi-organ failure and died. Two M-bands on serum capillary electrophoresis with presence IgG-κ on both the M-bands indicates a biclonal gammopathy of unknown significance in this patient. We conclude that like MGUS, early stage biclonal gammopathy, although rare, gets manifested with M-bands on plasma protein electrophoresis. It is probably due to high level of IL-6 associated with cytokine storm in severe COVID-19 that stimulate early stage dyscratic plasma cells. Such biclonal gammopathy might be a risk factor for severe COVID-19 and associated mortality.

Effect of sub-toxic exposure to Malathion on glucose uptake and insulin signaling in L6 myoblast derived myotubes.

Biochemical basis of Malathion exposure-induced diabetes mellitus is not known. Hence, effects of its sub-toxic exposure on redox sensitive kinases (RSKs), insulin signaling and insulin-induced glucose uptake were assessed in rat muscle cell line. In this in vitro study, rat myoblast (L6) cells were differentiated to myotubes and were exposed to sub-toxic concentrations (10 mg/l and 20 mg/l) of Malathion for 18 hours. Total antioxidant level and insulin-stimulated glucose uptake by myotubes were assayed. Activation of JNK, NFκB, p38MAPK and insulin signaling from tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and serine phosphorylation of Akt were assessed in myotubes after Malathion exposure by western blot and was compared with those in controls. Paraoxonase (PON) activity was measured in cell lysate using p-nitrophenyl acetate as substrate. PON1 and PON2 expression in myotubes were assessed by PCR. The glucose uptake and total antioxidant level in L6-derived myotubes after sub-toxic exposure to Malathion were decreased in a dose-dependent manner. Phosphorylation levels of RSKs (JNK, p38MAPK and IκBα component of NFκB) were increased and that of IRS-1 and Akt on insulin stimulation was decreased following Malathion exposure as compared to those in controls. PON1 and PON2 genes were expressed in myotubes with and without Malathion exposure. Significant PON activity was present in cell lysate. We conclude that sub-toxic Malathion exposure induces oxidative stress in muscle cells activating RSKs that impairs insulin signaling and thereby insulin-stimulated glucose uptake in muscle cells. This probably explains the biochemical basis of Malathion-induced insulin resistance state and diabetes mellitus.

Genetic affinities of the Jewish populations of India.

Due to the lack of written records or inscription, the origin and affiliation of Indian Jewish populations with other world populations remain contentious. Previous genetic studies have found evidence for a minor shared ancestry of Indian Jewish with Middle Eastern (Jewish) populations. However, these studies (relied on limited individuals), haven't explored the detailed temporal and spatial admixture process of Indian Jewish populations with the local Indian populations. Here, using large sample size with combination of high resolution biparental (autosomal) and uniparental markers (Y chromosome and mitochondrial DNA), we reconstructed genetic history of Indian Jewish by investigating the patterns of genetic diversity. Consistent with the previous observations, we detected minor Middle Eastern specific ancestry component among Indian Jewish communities, but virtually negligible in their local neighbouring Indian populations. The temporal test of admixture suggested that the first admixture of migrant Jewish populations from Middle East to South India (Cochin) occurred during fifth century. Overall, we concluded that the Jewish migration and admixture in India left a record in their genomes, which can link them to the 'Jewish Diaspora'.

Zhihengliuella somnathii sp. nov., a halotolerant actinobacterium from the rhizosphere of a halophyte Salicornia brachiata.

Two novel, Gram-stain-positive, rod-shaped, halotolerent bacteria, strains JG 03(T) and JG 05 were isolated from the rhizosphere of Salicornia brachiata, an extreme halophyte. Comparative analyses of 16S rRNA gene sequences showed that they were closely related to members of the genus Zhihengliuella, with sequence similarities of 96.9-99.1%. The sequence similarity of strains JG 03(T )and JG 05 with each other was 99.4%. DNA-DNA hybridization of JG 03(T) and JG 05 with other species of the genus Zhihengliuella with validly published names showed reassociation values of 19.8%-53.4% and a value of 91.4% between each other. The peptidoglycan type of both strains was A4α and MK-9 and MK-10 were the predominant menaquinones. The predominant fatty acid in JG 03(T) was anteiso-C15 : 0 and anteiso-C17 : 0. However, iso-C15 : 0, anteiso-C15 : 0 and anteiso-C17 : 0 were the major fatty acids in strain JG 05. The DNA G+C content of strains JG 03(T) and JG 05 was 70.0 and 70.1 mol%, respectively. In nutrient broth medium both strains grew at NaCl concentrations of up to 15% (w/v). On the basis of chemotaxonomic characteristics and phylogenetic analyses, strains JG 03(T) and JG 05 should be affiliated to the genus Zhihengliuella. Strains JG 03(T) and JG 05 represent a novel species of the genus Zhihengliuella for which the name Zhihengliuella somnathii sp. nov. is proposed. The type strain is JG 03(T) ( = DSM 23187(T) = IMCC 253(T)).