Correction to the pathogenic alternative splicing, caused by the common GNB3 c.825C>T allele, using a novel, antisense morpholino

The very common GNB3 c.825C>T polymorphism (rs5443), is present in approximately half of all human chromosomes. Significantly the presence of the GNB3 825T allele has been strongly associated, with predisposition to essential hypertension. Paradoxically the presence of the GNB3 825T allele, in exon 10, introduces a pathogenic alternative RNA splice site into the middle of exon 9. To attempt to correct this pathogenic aberrant splicing, we therefore bioinformatically designed, using a Gene Tools® algorithm, a GNB3 specific, antisense morpholino. It was hoped that this morpholino would behave in vitro as either a potential “ splice blocker and/or exon skipper, to both bind and inhibit/reduce the aberrant splicing of the GNB3, 825T allele. On transfecting a human lymphoblast cell line homozygous for the 825T allele, with this antisense morpholino, we encouragingly observed both a significant reduction (from ~58% to ~5%) in the production of the aberrant smaller GNB3 transcript, and a subsequent increase in the normal GNB3 transcript (from ~42% to ~95%). Our results demonstrate the potential use of a GNB3 specific antisense morpholino, as a pharmacogenetic therapy for essential hypertension

Targeting ATM pathway for therapeutic intervention in cancer

The Ataxia Telangiectasia Mutated gene encodes the ATM protein, a key element in the DNA damage response (DDR) signalling pathway responsible for maintaining genomic integrity within the cell. The ATM protein belongs to a family of large protein kinases containing the phosphatidylinositol-3 catalytic domain, including ATM, ATR and PI3K. ATM provides the crucial link between DNA damage, cell cycle progression and cell death by first sensing double stranded DNA breaks and subsequently phosphorylating and activating other downstream proteins functioning in DNA damage repair, cell cycle arrest and apoptotic pathways,. Mammalian cells are constantly challenged by genotoxic agents from a variety of sources and therefore require a robust sensing and repair mechanism to maintain DNA integrity or activate alternative cell fate pathways. This review covers the role of ATM in DDR signalling and describes the interaction of the ATM kinase with other proteins in order to fulfil its various functions. Special emphasis is given to how the growing knowledge of the DDR can help identify drug targets for cancer therapy, thus providing a rationale for exploiting the ATM pathway in anticancer drug development. Moreover, we discuss how a network modelling approach can be used to identify and characterise ATM inhibitors and predict their therapeutic potential

Prevalence and cause of gestational diabetes mellitus in a tertiary care center in Kolar district: a population based study

Background: Gestational diabetes mellitus (GDM) is carbohydrate intolerance at the onset of pregnancy which induces pathological short term or long term outcomes for both mother and baby. The aim of the present study was to know the prevalence of GDM in pregnant women who were attending the antenatal care (ANC) center at a tertiary care hospital in Kolar, Karnataka, India.Methods: This prospective study was conducted in Department of Obstetrics and Gynecology, Sri Devaraj Urs Medical College, a constituent of Sri Devaraj Urs Academy of Higher Education and Research, Kolar, Karnataka, India. The duration of the study was two months. In this study, 108 pregnant women above 24 weeks of gestation were screened for GDM by oral glucose tolerance test. Fasting 2 milli liter blood was collected and were given 75 grams of glucose in 200 milli liters of water and asked to drink within 5 minutes. Again 2 milli liters venous blood was collected after 1 hour and 2 hours from all participants. Plasma sample was used for the estimation of glucose by glucose oxidase and peroxidase (GOD-POD) method.Results: Out of 108, 12 women (11.1%) were diagnosed with GDM. The prevalence rate was higher in the age group of 26-30 years (41.6%).  Among 12 diabetic women, five (47.2%) exercised regularly and seven (58.3%) did not doing exercise. Out of 12 GDM subjects, eight of them had family history of diabetes in first degree relatives; among which one was hypertensive and five were suffering from thyroid problems.Conclusions: In the present study, the prevalence of GDM was found to be 11.1%. Prevalence of GDM might be influenced by increasing age, pre pregnancy weight, family history of diabetes, past history of pregnancy complications, status of literacy and exercise

Intracranial Aneurysms: Review of Current Treatment Options and Outcomes

Intracranial aneurysms are present in roughly 5% of the population, yet most are often asymptomatic and never detected. Development of an aneurysm typically occurs during adulthood, while formation and growth are associated with risk factors such as age, hypertension, pre-existing familial conditions, and smoking. Subarachnoid hemorrhage, the most common presentation due to aneurysm rupture, represents a serious medical condition often leading to severe neurological deficit or death. Recent technological advances in imaging modalities, along with increased understanding of natural history and prevalence of aneurysms, have increased detection of asymptomatic unruptured intracranial aneurysms (UIA). Studies reporting on the risk of rupture and outcomes have provided much insight, but the debate remains of how and when unruptured aneurysms should be managed. Treatment methods include two major intervention options: clipping of the aneurysm and endovascular methods such as coiling, stent-assisted coiling, and flow diversion stents. The studies reviewed here support the generalized notion that endovascular treatment of UIA provides a safe and effective alternative to surgical treatment. The risks associated with endovascular repair are lower and incur shorter hospital stays for appropriately selected patients. The endovascular treatment option should be considered based on factors such as aneurysm size, location, patient medical history, and operator experience

High loading of nanostructured ceramics in polymer composite thick films by aerosol deposition

Low temperature fabrication of Al2O3-polyimide composite substrates was carried out by an aerosol deposition process using a mixture of Al2O3 and polyimide starting powders. The microstructures and dielectric properties of the composite thick films in relation to their Al2O3 contents were characterized by X-ray diffraction analysis. As a result, the crystallite size of α-Al2O3 calculated from Scherrer's formula was increased from 26 to 52 nm as the polyimide ratio in the starting powders increased from 4 to 12 vol.% due to the crushing of the Al2O3 powder being reduced by the shock-absorbing effect of the polyimide powder. The Al2O3-polyimide composite thick films showed a high loss tangent with a large frequency dependence when a mixed powder of 12 vol.% polyimide was used due to the nonuniform microstructure with a rough surface. The Al2O3-polyimide composite thick films showed uniform composite structures with a low loss tangent of less than 0.01 at 1 MHz and a high Al2O3 content of more than 75 vol.% when a mixed powder of 8 vol.% polyimide was used. Moreover, the Al2O3-polyimide composite thick films had extremely high Al2O3 contents of 95 vol.% and showed a dense microstructure close to that of the Al2O3 thick films when a mixed powder of 4 vol.% polyimide was used

Effectiveness of Fluorography Versus Cineangiography at Reducing Radiation Exposure During Diagnostic Coronary Angiography

Coronary angiography is the gold standard for defining obstructive coronary disease. However, radiation exposure remains an unwanted hazard. Patients referred for coronary angiography with abdominal circumference60 ml/min were randomized to the fluorography (n = 25) or cineangiography (n = 25) group. Patients in the fluorography group underwent coronary angiography using retrospectively stored fluorography with repeat injection under cineangiography only when needed for better resolution per operator\u27s discretion. Patients in the cineangiography group underwent coronary angiography using routine cineangiography. The primary end point was patient radiation exposure measured by radiochromic film. Secondary end points included the radiation output measurement of kerma-area product and air kerma at the interventional reference point (Ka,r) and operator radiation exposure measured by a dosimeter. Patient radiation exposure (158.2 mGy [76.5 to 210.2] vs 272.5 mGy [163.3 to 314.0], p = 0.001), kerma-area product (1,323 mu Gy.m(2) 1826 to 1,765] vs 3,451 mu Gy.m(2) [2,464 to 4,818], p \u3c 0.001), and Ka,r (175 mGy [112 to 252] vs 558 mGy [313 to 621], p \u3c 0.001) were significantly lower in the fluorography compared with cineangiography group (42%, 62%, and 69% relative reduction, respectively). Operator radiation exposure trended in the same direction, although statistically nonsignificant (fluorography 2.35 mu Gy [1.24 to 6.30] vs cineangiography 5,03 mu Gy 12.48 to 7.80], p = 0.059). In conclusion, the use of fluorography in a select group of patients during coronary angiography, with repeat injection under cineangiography only when needed, was efficacious at reducing patient radiation exposure. (C) 2014 Elsevier Inc. All rights reserved

Tungabhadra Left Bank Canal (TLBC) irrigation modernization: Detailed command area mapping using remote sensing, (November 2018 - March 2019)

Conventional surveys and assessments have merged with technology to help decision makers take timely action and prevent losses in agricultural production. Remote sensing is one such technology-driven tool that can produce accurate results economically. So is satellite imagery with high temporal and spatial resolutions specifically suited to agriculture. Given Karnataka state’s diverse agro-ecosystems, knowing the spatial distribution of such systems and their constraints to production is essential so that abiotic stresses like drought can be mapped and information disseminated to decision makers for contingency planning. The natural resource base of an area is instrumental in its agricultural development and also linked to improvement of livelihoods. Mapping the natural resource base and crop domains provides insights into the status of and trends in land and water utilization, development of water resources over time, and the impacts of cropping systems on water resource systems (Gumma et al. 2016a; Gumma et al. 2011a). Integrating remote sensing with spatial analyses like crop and economic models provides the much needed knowledge for decision making for resource-based planning of lower risk and profitable cropping systems, efficient allocation of water at basin and sub-basin levels and other crop management interventions in targeting technologies appropriate for different locations. Remote sensing provides such information in a time and cost effective manner by mapping major cropped areas using open datasets such as MODIS, LANDSAT, along with high resolution datasets from Indian remote sensing satellites, and sensors such as LISS IV and RiSAT-1 which provide reliable information on spatial distribution, acreage estimation and crop growth stages (during planting and harvesting)..

Germline heterozygous DDX41 variants in a subset of familial myelodysplasia and acute myeloid leukemia

The Brazilian National Council for Scientific and Technological Development), Bloodwise, Children with Cancer and MRC (Medical Research Council, UK)