Geographical and chronological origin and evolution of Hepatitis C Virus.

Hepatitis C Virus (HCV) infection is a major health problem that leads to cirrhosis and hepatocellular carcinoma. World over, more than 270-300 million people are estimated to be infected with the virus. HCV is a positive sense single stranded RNA virus and replicates within the cytoplasm of the hepatocyte using its own RNA dependent RNA polymerase (RdRp). RdRp does not have proof reading capacity, and hence generates mutants of the virus, resulting in a chronic infection, which ultimately ends in hepatocellular carcinoma. Such mutations have given rise to several genotypes, subtypes, strains and variants with significant difference in disease outcomes. The mutation rate varies among genotypes, subtypes, strains or even in different sites of the genome. Yet, the extent of heterogeneity is usually moderate, so that estimates of the time of divergence can be computed. The evolution of variants seems to be influenced by the genetic make-up and the immune response of the host and has geographical significance. Here we used phylogenetic analysis and Computational molecular dating techniques to conclude that the ancestral genotype is 7a and that it originated in Canada 363 years ago. Molecular dating was based on the fact that the rate of mutation across all evolutionary lineages is constant over time. Surprisingly, our analyses show that genotype 1d isolated from Canada5 is the most recent with an evolutionary date of just 33 years. It is evident that HCV is still an emerging virus and demographical parameters seem to have a very strong influence in its evolution. We believe that this emphasises the need for developing drugs that are customised to act against strains that evolve and become geographically endemic

Virtual screening for NS5B inhibitors of Hepatitis C virus

Hepatitis C Virus (HCV) infection is a serious cause of chronic liver disease worldwide with more than 170 million infected individuals at a risk of developing significant morbidity and mortality. To date there is no effective drug for the treatment or vaccine to prevent this infection. The present study aims to discover novel inhibitors which target an allosteric binding site of RNA dependent RNA polymerase enzyme of HCV. A structure based virtual screening of Zinc database by computational docking and the post docking analysis of energy calculations and interactions followed by ADMET studies were conducted. Our study revealed 10 compounds which has more potential than the existing inhibitor to be considered as lead compounds.
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Selective C-methylation of phenol with methanol over transition metals modified mesoporous ceria catalysts

The demand for selective catalysts with larger molecular dimensions led to the discovery of mesoporous catalytic materials. We report herein the development of an environmentally friendly process for C-methylation of phenol derivatives with methanol using mesoporous ceria modified with transition metals.  Selective C-methylation of phenol, has been investigated over transition metals loaded mesoporous ceria. Catalyst reaction rates at various reaction parameters were also investigated. 98% selectivity for ortho-alkylated products (o-cresol and 2, 6-xylenol) was obtained. The reaction is proved to be first order with phenol conversion. The frequency factor A and the activation energy Ea were also evaluated with (CeFe10%) catalyst

NEUTRACUETICAL EVALUATION OF BOERHAVIA DIFFUSA L.

Objective: Boerhavia diffusa a tropical herb has been a subject of keen interest in phytochemical and pharmacological research due to its excellent medicinal values. The stress and need for quality control and standardisation of medicinal preparations from plants is gaining more importance today in view of the commercialization of drug formulations.Methods: WHO recommends various physicochemical, proximate and nutritive standards so that uniformity in composition and effectiveness is maintained? All the analysis was done using standard protocols.Results: The nutraceutical evaluation of the plant gives an insight into its value as a medicinal as well as highly nutritious one, safe for consumption both as a medicine and as a natural source for antioxidant activities.Conclusion: Thus the present finding suggests that B. diffusa have a promising potential not only to cure ailments but to maintain a healthy life

Chromia Modified Sol-gel Titania as Catalysts for Wet Peroxide Oxidation of Phenol

Wet peroxide oxidation of phenol was carried out over chromia modified sol-gel titania. An added advantage of this method is the removal of phenol from waste water effluents. The influence of solvent, reaction temperature, reaction time, catalyst amount and the molar ratio of phenol to hydrogen peroxide were investigated intensively. An initial induction period is noticed in all the cases. A thorough study on the reaction variables suggests free radical mechanism of the reaction. Physico-chemical characterizations of the prepared systems were done using powder XRD, EDX, BET surface area-pore volume measurements and TG-DTG analysis

Rodenticide poisoning in children: A study of clinical profile and electrocardiographic changes

Objectives: To study the clinical profile and electrocardiographic (ECG) changes in rodenticide poisoning in children. Methods: Patients admitted with a history of ingestion of rat poison between October 2014 and October 2016 were included in the study. Clinical history was taken in detail, and stomach wash samples were sent for toxicological analysis. Continuous ECG monitoring was done in all cases. Investigations to assess organ functions and coagulation profile were done at admission and repeated as indicated. Results: There were 17 cases of rodenticide poisoning. Zinc phosphide was the rodenticide identified in 50% of cases, bromodiolone in 30%, and yellow phosphorous in 20% cases. Only 23% presented within 1 h of ingestion and only 12% received stomach wash from referring hospital. Out of the 17 cases, 12 cases (70%) were symptomatic, of which 42% hadminor symptoms such as vomiting and abdominal pain and 58% had major symptoms including dysrhythmias, shock, coagulation abnormality, hepatic failure, and seizures. ECG changes were observed in 7 cases (42%), and coagulopathy was seen in 2 (12%) cases of which one had hepatic failure. The mean time of onset of ECG changes was 19.7 h (range 9-36 h). The overall mortality rate was 17.6%. Cardiac arrhythmia was the most common cause of death (66%). Conclusion: Zinc phosphide has been detected as the most common chemical being used as domestic rodenticide. Transient rate abnormalities, metabolic acidosis, fever, and leukocytosis are early markers of toxicity and they should be looked for in all cases. General public, medical, and aramedicalpersonnel should be made aware of the toxic nature of rodenticides

Liquid Phase Benzylation of Toluene over Modified Titania Catalysts

Titania, sulfated titania and a series of iron loaded sulfated titania catalyst with different iron loadings (39 %) are prepared by sol-gel method and calcined at 500°C. Anatase is found to be the active phase with crystallite size in the nano range. All the prepared catalysts are found to be stable up to 700°C. Acidity is measured using spectrophotometric monitoring of adsorption of perylene, thermogravimetric desorption of 2,6-dimethylpyridine and temperature programmed desorption of ammonia. The activities of the catalysts were tested for liquid phase Friedel-Crafts benzylation of toluene with benzyl chloride. It has been concluded that Lewis acid sites are responsible for the reaction

Inhibition of the mitochondrial calcium uniporter (MCU) rescues dopaminergic neurons in pink1-/- zebrafish

Mutations in PTEN-induced putative kinase 1 (PINK1) are a cause of early onset Parkinson's disease (PD). Loss of PINK1 function causes dysregulation of mitochondrial calcium homeostasis, resulting in mitochondrial dysfunction and neuronal cell death. We report that both genetic and pharmacological inactivation of the mitochondrial calcium uniporter (MCU), located in the inner mitochondrial membrane, prevents dopaminergic neuronal cell loss in pink1Y431* mutant zebrafish (Danio rerio) via rescue of mitochondrial respiratory chain function. In contrast, genetic inactivation of the voltage dependent anion channel 1 (VDAC1), located in the outer mitochondrial membrane, did not rescue dopaminergic neurons in PINK1 deficient Danio rerio. Subsequent gene expression studies revealed specific upregulation of the mcu regulator micu1 in pink1Y431* mutant zebrafish larvae and inactivation of micu1 also results in rescue of dopaminergic neurons. The functional consequences of PINK1 deficiency and modified MCU activity were confirmed using a dynamic in silico model of Ca2+ triggered mitochondrial activity. Our data suggest modulation of MCU-mediated mitochondrial calcium homeostasis as a possible neuroprotective strategy in PINK1 mutant PD

Some considerations concerning the challenge of incorporating social variables into epidemiological models of infectious disease transmission

Incorporation of ‘social’ variables into epidemiological models remains a challenge. Too much detail and models cease to be useful; too little and the very notion of infection —a highly social process in human populations—may be considered with little reference to the social. The French sociologist Emile Durkheim proposed that the scientific study of society required identification and study of ‘social currents.’ Such ‘currents’ are what we might today describe as ‘emergent properties,’ specifiable variables appertaining to individuals and groups, which represent the perspectives of social actors as they experience the environment in which they live their lives. Here we review the ways in which one particular emergent property, hope, relevant to a range of epidemiological situations, might be used in epidemiological modelling of infectious diseases in human populations. We also indicate how such an approach might be extended to include a range of other potential emergent properties to repre