Use of proton pump inhibitors in dialysis unit in tertiary care hospital: a pharmaco-epidemiological study

Background: Proton pump inhibitors (PPI) are generally thought to be safer drug with fewer adverse effects. Though this class of the drug is thought to be well tolerated, a detail study about actual use of these agents in nephrology department is still awaited in many parts of India. There had been case reports and case series which were reporting PPIs producing acute interstitial nephritis progressing to acute renal failure. The risk of PPI treatment in haemodialysis patients remains unexplored. The aim of the study was to evaluate a drug utilization of PPI in patient undergoing haemodialysis procedure.Methods: In this study every day visit to the dialysis units of the hospitals was carried out. After taking consent from the patients, the information from the case-report form was noted like; age, sex, diagnosis, laboratory reports and drug prescried. No personally identifiable information about patient or physician was collected. After this an interview of patients was taken.Results: In this study, out of 126 patients 76.6% were male and 23.4% were female. Out of these 126 patients 88.89% patients were on PPI. Nearly 54% were using PPI for more than six months. Nearly 29% patients were using PPI for more than 12 months.Conclusions: As many case-reports and studies are suggesting, there is co-relation of PPI and acute interstitial nephritis from this study we suggest that especially in nephrology unit patients’, more caution must be exercised while using PPI

Processing Big Data Applications using MapReduce

The term Big data is one of the important terms now days for every sector. As there are no. of organizations starts generating huge amount of data so there is a need of having some processing as well as storage engine. The term big data a collection of massive, huge  and complex data sets which includes the large quantities of data, social media its analysis, data management as well as real time data. To fetch and extract the use full data or to derive some conclusion from the Big data, analysis of the data in proper manner is required. So, this analysis can be done with different techniques one of them is Hadoop. And more specifically a MapReduce Framework

Genetic analysis of SLC47A1, SLC22A1, SLC22A2, ATM gene polymorphisms among diabetics in an Indian population

Background: Metformin is a first-line therapy for type 2 diabetes mellitus. However, the glycaemic response to metformin is likely to be affected by polymorphisms of transporter genes. Therefore, the study was done with the  aim to assess demographic distribution of transporter genotypes involved in disposition and action of metformin.Methods: This cross-sectional, observational, single centre, clinical study was conducted in 80 diabetic patients recruited from medicine OPD. Descriptive analysis was done for distribution of the four transporter genotypes viz. SLC47A1 (rs2289669), ATM (rs11212617), SLC22A2 (rs316019) and SLC22A1 (rs622342). Genotyping was determined by DNA extraction, agarose gel electrophoresis, estimation of DNA concentration, polymerase chain reaction, DNA sequencing, sequencing analysis.Results: Transporter genotype analysis showed that for SLC47A1 (rs2289669) transporter, 31.25% and 26.25% were homozygous for AA and GG allele respectively, while 42.5% were heterozygous (AG). For ATM (rs11212617), SLC22A2 (rs316019) and SLC22A1 (rs622342) transporter, 45% and 10%, 1.25% and 80%, 58.75% and 7.50% were homozygous for AA and CC allele respectively; while 45%, 18.75%, 33.75% were heterozygous (AC) respectively. Interethnic differences in the genotype and allele frequencies of SLC22A1 (rs622342) and ATM (rs11212617) gene polymorphism were observed when compared with other major populations.Conclusions: In the genotypic distribution of four transporter genotype study showed that there was an ethnic variation in allelic distribution of allele A and C of ATM (rs11212617) and SLC22A1 (rs622342) while AA genotype of SLC22A2 (rs316019) was rare genotype and allele ‘A’ was major allele found in our study. The study data observed would justify further pharmacogenetic studies to evaluate the role of gene polymorphism in the therapeutic efficacy of metformin.

Ultra Thin White Topping

Paper consists of subsistence of highway road and improvement in low cost and increasing the strength and vitality of the pavement. Ultra-Thin White Topping may be defined as a concrete cover with closely spaced joints and bonded to an existing bituminous pavement. It consists of a fine layer of high durability, fibre-reinforced concrete laid over a clean, milled surface of distressed bituminous concrete pavement, to achieve full or partial bonding. From the degradation summary it is identified that even after 10 years, the riding quality of Ultra-Thin White Topping is the most admirable and the most desirable one without any mediation. Structural collapse emerges from the action that contrarily affects the traffic volume carrying capacity of the pavement. This structural collapse can be overcome by using Ultra-Thin White Topping pavement over bituminous pavement. Ultra-Thin White Topping achieves very low End User Cost values thus resulting in the maximization of Gross Economic Benefits than that of ordinary bitumen overlay

Ion-Abrasion Scanning Electron Microscopy Reveals Surface-Connected Tubular Conduits in HIV-Infected Macrophages

HIV-1-containing internal compartments are readily detected in images of thin sections from infected cells using conventional transmission electron microscopy, but the origin, connectivity, and 3D distribution of these compartments has remained controversial. Here, we report the 3D distribution of viruses in HIV-1-infected primary human macrophages using cryo-electron tomography and ion-abrasion scanning electron microscopy (IA-SEM), a recently developed approach for nanoscale 3D imaging of whole cells. Using IA-SEM, we show the presence of an extensive network of HIV-1-containing tubular compartments in infected macrophages, with diameters of ∼150–200 nm, and lengths of up to ∼5 µm that extend to the cell surface from vesicular compartments that contain assembling HIV-1 virions. These types of surface-connected tubular compartments are not observed in T cells infected with the 29/31 KE Gag-matrix mutant where the virus is targeted to multi-vesicular bodies and released into the extracellular medium. IA-SEM imaging also allows visualization of large sheet-like structures that extend outward from the surfaces of macrophages, which may bend and fold back to allow continual creation of viral compartments and virion-lined channels. This potential mechanism for efficient virus trafficking between the cell surface and interior may represent a subversion of pre-existing vesicular machinery for antigen capture, processing, sequestration, and presentation

Constraints on the shallow elastic and anelastic structure of Mars from InSight seismic data

Mars’s seismic activity and noise have been monitored since January 2019 by the seismometer of the InSight (Interior Exploration using Seismic Investigations, Geodesy and Heat Transport) lander. At night, Mars is extremely quiet; seismic noise is about 500 times lower than Earth’s microseismic noise at periods between 4 s and 30 s. The recorded seismic noise increases during the day due to ground deformations induced by convective atmospheric vortices and ground-transferred wind-generated lander noise. Here we constrain properties of the crust beneath InSight, using signals from atmospheric vortices and from the hammering of InSight’s Heat Flow and Physical Properties (HP3) instrument, as well as the three largest Marsquakes detected as of September 2019. From receiver function analysis, we infer that the uppermost 8–11 km of the crust is highly altered and/ or fractured. We measure the crustal diffusivity and intrinsic attenuation using multiscattering analysis and find that seismic attenuation is about three times larger than on the Moon, which suggests that the crust contains small amounts of volatiles

Laparoscopic Bilateral Adrenalectomy in a patient of Cushing syndrome: A Challenge for the Anaesthesiologist

We present a case of Cushing syndrome who underwent laparoscopic bilateral adrenalectomy and discuss her intraoperative management and postoperative course in ICU, especially pulmonary oedema, that occurred within 3 hours after resection (half life of cortisol is 80-110 minutes). [1] She was diagnosed to have bilateral adrenal hyperplasia with no pituitary involvement on CT scan. Preoperative workup revealed hypokalemia, anaemia, hypertension and hyperglycemia. She was posted for laparoscopic bilateral adrenalectomy. She received general anaesthesia; we did not give epidural analgesia as the patient had fracture of body of L1 vertebrae. Her intra-operative course was uneventful. Post-operative concerns included acute adrenal insufficiency, hypoglycaemia, hypotension and hyperkalemia, which were successfully managed in ICU. Patient was then given oral corticosteroids. One month later she was reassessed and was in better health

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BACE-1 inhibition by protriptyline.

<p><b>A</b>. Determination of IC50 of BACE-1 by using various concentrations of protriptyline. The sigmoidal curve indicates the best fit for the percentage inhibition data obtained <b>B</b>. Lineweaver-Burk analysis to estimate the kinetic constants. It showed competitive inhibition. <b>C</b>. Snapshot of drug binding with active site of BACE-1. Active site residues in BACE-1 are in line representation. <b>D</b>. Active site of BACE-1. The structures from unbound (green) and ligand bound (orange) simulations are shown after all - atom superimposition. Snapshots are generated using PyMol.</p

Molecular Investigations of Protriptyline as a Multi-Target Directed Ligand in Alzheimer's Disease

<div><p>Alzheimer's disease (AD) is a complex neurodegenerative disorder involving multiple cellular and molecular processes. The discovery of drug molecules capable of targeting multiple factors involved in AD pathogenesis would greatly facilitate in improving therapeutic strategies. The repositioning of existing non-toxic drugs could dramatically reduce the time and costs involved in developmental and clinical trial stages. In this study, preliminary screening of 140 FDA approved nervous system drugs by docking suggested the viability of the tricyclic group of antidepressants against three major AD targets, viz. Acetylcholinesterase (AChE), β-secretase (BACE-1), and amyloid β (Aβ) aggregation, with one member, protriptyline, showing highest inhibitory activity. Detailed biophysical assays, together with isothermal calorimetry, fluorescence quenching experiments, kinetic studies and atomic force microscopy established the strong inhibitory activity of protriptyline against all three major targets. The molecular basis of inhibition was supported with comprehensive molecular dynamics simulations. Further, the drug inhibited glycation induced amyloid aggregation, another important causal factor in AD progression. This study has led to the discovery of protriptyline as a potent multi target directed ligand and established its viability as a promising candidate for AD treatment.</p></div