Impact of media: self-medication and the rising problem of antimicrobial resistance

Antimicrobial agents (AMAs) are one of the most commonly used as well as misused drugs. Antimicrobial resistance is an important growing global health issue which needs urgent addressal.Self-medication involves the use of medicinal products by the patient to treat self-recognized disorders, symptoms, recurrent diseases, or minor health problems. Medicines for self-medication are often called over the counter (OTC) drugs, which are available without a doctor’s prescription through pharmacies, mostly in the developing countries. Self-medication particularly with antibiotics has been widely reported, leading the World Health Organization to call attention to its dangers as a cause of antimicrobial resistance

[C I] and [C II] emission in the circumstellar envelope of IRC +10216 I. Observational data and NLTE modeling of the [C I] emission

Aims: The study at hand aims to describe the distribution of atomic carbon, C0, throughout the envelope, in support of an improved understanding of its photo-chemistry. Additionally, we also briefly discuss the observation of [CII] emission towards the star. Methods: We obtain spectra of the [CI] $\mathrm{^3P_1} \rightarrow \mathrm{^3P_0}$ fine structure line at projected distances of up to 78" from the star. The line profiles are characterized by both direct fitting of Gaussian components, and by modeling the observed line of the [CI] triplet. We also report the detection of the $\mathrm{^2P_{3/2}} \rightarrow \mathrm{^2P_{1/2}}$ line from the C+ fine structure singlet at the central position and at 32" from the star. Results: The overall picture of the [CI] emission from IRC +10216 agrees with more limited previous studies. The satisfying agreement between the observed and modeled line profiles, with emission at the systemic velocity appearing beyond one beam from the star, rules out that the C0 is located in a thin shell. Given that the bond energy of CO falls only 0.1 eV below the ionization threshold of C0, the absence of observable [CII] emission from sightlines beyond a projected distance of $\sim 10^{17}$ cm from the star (adopting a distance of 130 pc) does not contradict a scenario where the bulk of C0 is located between that of CO and C+, as expected for an external FUV radiation field. This conjecture is also corroborated by a model in which the C0 shell is located farther outside, failing to reproduce the [CI] line profiles at intermediate sky-plane distances from the star. Comparing a photo-chemical model adopted from literature with the simplifying assumption of a constant C0 abundance with respect to the $\mathrm{H}_2$ density, we constrain the inner boundary of the [CI] emitting shell, located at $\sim 10^{16}$ cm from the star.Comment: 10 pages, 7 figures, accepted for publication in A&

SPEECH CONTROLLED ROBOCAR

The main goal of this paper is to introduce “hearing” sensor and also the speech synthesis to the robotic car such that it is capable to interact with human through Spoken Natural Language (NL). Speech recognition (SR) is a prominent technology, which helps us to introduce “hearing” as well as Natural Language (NL) interface through Speech for the interaction. The most challenging part of the entire system is designing and interfacing various stages together. Our approach was to get the analog voice signal being digitized. The frequency and pitch of words be stored in a memory. These stored words will be used for matching with the words spoken. When the match is found, the system outputs the address of stored words. Hence we have to decode the address and according to the address sensed, the car will perform the required task. Since we wanted the car to be wireless, we used RF module. The address was decoded using microcontroller (DSPIC30F) and then applied to RF module. This together with driver circuit at receivers end made complete intelligent systems

Comparative Study of Modified Quantitative Buffy Coat and Two Rapid Tests in Comparison with Peripheral Blood Smear in Malaria Diagnosis in Mumbai, India

In order to identify a quick and reliable technique for accurate diagnosis of malaria, study of the efficiency of the tests such as Parahit total (HRPII & aldolase Ag), Advantage mal card (parasite specific LDH), and modified QBC was done in comparison with conventional blood smear microscopy. One hundred patients infected with P. vivax and 101 infected with P. falciparum were included in this study. The sensitivity of Parahit total, Advantage mal card, and modified QBC for P. falciparum detection was 70.3, 95%, and 98%, and specificity was 98%, 98%, and 96%, respectively. The sensitivity of Parahit total, Advantage mal card, and modified QBC for P. vivax detection was 73%, 97.0%, and 98%, respectively, and specificity of all the tests was 98%. On day 15, in falciparum arm, Advantage mal card and Parahit total showed 8 (7.92%) and 59 (58.41%) false positives. On day 15, in vivax arm, Parahit total revealed 52% false positives. The study indicated that modified QBC could be only used where appropriate facilities are available. Advantage mal card was a better follow-up tool than Parahit total

Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 (BMPR2) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. METHODS: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource-Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of <1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. RESULTS: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (Kco; 33% [interquartile range, 30%-35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23-38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. CONCLUSIONS: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low Kco and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation

BionoiNet: Ligand-binding site classification with off-the-shelf deep neural network

© The 2020 Author(s). Published by Oxford University Press. All rights reserved. Motivation: Fast and accurate classification of ligand-binding sites in proteins with respect to the class of binding molecules is invaluable not only to the automatic functional annotation of large datasets of protein structures but also to projects in protein evolution, protein engineering and drug development. Deep learning techniques, which have already been successfully applied to address challenging problems across various fields, are inherently suitable to classify ligand-binding pockets. Our goal is to demonstrate that off-the-shelf deep learning models can be employed with minimum development effort to recognize nucleotide-and heme-binding sites with a comparable accuracy to highly specialized, voxel-based methods. Results: We developed BionoiNet, a new deep learning-based framework implementing a popular ResNet model for image classification. BionoiNet first transforms the molecular structures of ligand-binding sites to 2D Voronoi diagrams, which are then used as the input to a pretrained convolutional neural network classifier. The ResNet model generalizes well to unseen data achieving the accuracy of 85.6% for nucleotide-and 91.3% for heme-binding pockets. BionoiNet also computes significance scores of pocket atoms, called BionoiScores, to provide meaningful insights into their interactions with ligand molecules. BionoiNet is a lightweight alternative to computationally expensive 3D architectures

Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease

Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in $\textit{CHM}$ in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease.This work was supported by The National Institute for Health Research England (NIHR) for the NIHR BioResource – Rare Diseases project (grant number RG65966). The Moorfields Eye Hospital cohort of patients and clinical and imaging data were ascertained and collected with the support of grants from the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital, National Health Service Foundation Trust, and UCL Institute of Ophthalmology, Moorfields Eye Hospital Special Trustees, Moorfields Eye Charity, the Foundation Fighting Blindness (USA), and Retinitis Pigmentosa Fighting Blindness. M.M. is a recipient of an FFB Career Development Award. E.M. is supported by UCLH/UCL NIHR Biomedical Research Centre. F.L.R. and D.G. are supported by Cambridge NIHR Biomedical Research Centre

The Burden of Progressive Fibrosing Interstitial Lung Disease: A DELPHI Approach

Introduction: The term progressive fibrosing interstitial lung disease (ILD) describes patients with fibrotic ILDs who, irrespective of the aetiology of the disease, show a progressive course of their disease despite current available (and non-licensed) treatment. Besides in idiopathic pulmonary fibrosis, little is known about management and the burden of patients with fibrotic ILD, particularly those with a progressive behaviour. Methods: Using the Delphi method, 40 European experts in ILD management delivered information on management of (progressive) fibrosing ILD and on the impact of the disease on patients’ quality of life (QoL) and healthcare resource utilisation (HCRU). Annual costs were calculated for progressive and non-/slow-progressive fibrosing ILD for diagnosis, follow-up management, exacerbation management, and end-of-life care based on the survey data. Results: Physicians reported that progression in fibrosing ILD worsens QoL in both patients and their caregivers. Progression of fibrosing ILD was associated with a greater use of HCRU for follow-up visits and maintenance treatment compared with the non-/slow progression. The number of patients who suffered at least one acute exacerbation was reported to be more than three times higher in progressive fibrosing ILD patients than in patients with non-/slow-progressive fibrosing ILD. On average, annual estimated costs of progressive fibrosing ILD per patient were 1.8 times higher than those of the non-/slow-progressive form of the disease.