A Clinico-Epidemiological Study of Cutaneous Adverse Drug Reactions in a Tertiary Care Centre of Eastern India.

Background: Adverse drug reactions (ADRs) are major problems in the drug therapy. Cutaneous adverse drug reactions (CADRs) are the most common ADRs. The pattern of CADRs differs among various drugs. Aims: To record various morphological patterns of CADRs and their causal relationships among patients attending in a tertiary care centre. Materials and Methods: An observational, cross-sectional, clinical study was conducted for a duration of one and a half years in a tertiary care centre in eastern India. Patients presenting with suspected CADRs were included if drug identity could be ascertained. Clinical profiling and drug history were recorded, and causality assessment was carried out as per the Naranjo scale. Result: The commonest CADR in our study was fixed drug eruption (FDE) 48.61%, followed by SJS-TEN spectrum 16.66%, maculopapular rash 11.11% and so on. Severe cutaneous adverse drug reactions (SCARs) such as SJS, TEN, SJS-TEN Overlap, AGEP and DRESS accounted for 18 cases (25%). The most common culprit drugs were antimicrobials (54.16%), followed by nonsteroidal anti-inflammatory drugs (15.27%) and anticonvulsants (12.5%). Most of the CADRs were in probable category. Conclusion: The pattern of CADRs and the drugs causing them in our study population are similar to some previous studies but somewhat different from most of the previous Indian studies. The incidence of SCARs was significantly higher than in previous other studies in India and abroad.

Overview of the National Ethics Committee Registry for Biomedical and Health Research in India: Stepping up to safeguard the ethical aspect of research involving human participants.

As notified in the New Drugs and Clinical Trials Rules 2019, ethics committees (ECs), intending to review and oversee the conduct of Biomedical and Health Research (BHR) shall be required to register with the authority designated by the Central Government in the Ministry of Health and Family Welfare, Department of Health Research (DHR). The entire process of receiving and processing such applications is done online through the Naitik portal. Vide these rules, it has become mandatory for all institutions/entities whether publicly or privately conducting or intending to conduct BHR involving the human participants, to get their EC, registered with the DHR. A status report of the functioning of the National Ethics Registry and an analysis of ECs registered with the DHR are presented in this manuscript. A workflow of the processing involved in EC registration is given with sectorial segregation, and analysis of data on ECs across the country is made for the dissemination and information. This article elaborates on the registration requirements and process of the EC registry with the necessity of being registered with the DHR. 2100 login requests and more than 1560 applications for registration have been received; private hospitals and medical colleges have been the front-runner in getting their organization registered, and organizations in the commercial sector are faring better in terms of EC registration. Further dissemination and outreach efforts have to be made to draw the attention of various stakeholders regarding this requirement and thereby ensuring that all ECs in the country are registered with the DHR.

Unveiling the need of interactions for social N400s and supporting the N400 inhibition hypothesis.

When participants (Pps) are presented with stimuli in the presence of another person, they may consider that person's perspective. Indeed, five recent ERP studies show that the amplitudes of their N400s are increased. The two most recent ones reveal that these social-N400 increases occur even when instructions do not require a focus on the other's perspective. These increases also happen when Pps know that this other person has the same stimulus information as they have. However, in all these works, Pps could see the other person. Here, we tested whether the interaction occurring with this sight is important or whether these social N400 increases also occur when the other person is seated a bit behind Pps, who are aware of it. All had to decide whether the word ending short stories was coherent, incoherent, or equivocal. No social N400 increase was observed: N400s elicited by those words in Pps who were with a confederate (n = 50) were similar to those of Pps who were alone (n = 51). On the other hand, equivocal endings did not elicit larger N400s than coherent ones but triggered larger late posterior positivities (LPPs), like in previous studies. The discussion focuses on the circumstances in which perspective-taking occurs and on the functional significance of the N400 and the LPP.

Time-Frequency Analysis of Scalp EEG With Hilbert-Huang Transform and Deep Learning.

Electroencephalography (EEG) is a brain imaging approach that has been widely used in neuroscience and clinical settings. The conventional EEG analyses usually require pre-defined frequency bands when characterizing neural oscillations and extracting features for classifying EEG signals. However, neural responses are naturally heterogeneous by showing variations in frequency bands of brainwaves and peak frequencies of oscillatory modes across individuals. Fail to account for such variations might result in information loss and classifiers with low accuracy but high variation across individuals. To address these issues, we present a systematic time-frequency analysis approach for analyzing scalp EEG signals. In particular, we propose a data-driven method to compute the subject-specific frequency bands for brain oscillations via Hilbert-Huang Transform, lifting the restriction of using fixed frequency bands for all subjects. Then, we propose two novel metrics to quantify the power and frequency aspects of brainwaves represented by sub-signals decomposed from the EEG signals. The effectiveness of the proposed metrics are tested on two scalp EEG datasets and compared with four commonly used features sets extracted from wavelet and Hilbert-Huang Transform. The validation results show that the proposed metrics are more discriminatory than other features leading to accuracies in the range of 94.93% to 99.84%. Besides classification, the proposed metrics show great potential in quantification of neural oscillations and serving as biomarkers in the neuroscience research.

A Comparative Study to Evaluate the Efficacy and Cost of Rituximab versus Dexamethasone Cyclophosphamide Pulse in Patients of Pemphigus Vulgaris.

INTRODUCTION: Rituximab is slowly getting recognized as a promising steroid-sparing agent in the treatment of moderate to severe cases of pemphigus vulgaris (PV). We evaluated and compared the effectiveness, safety, and cost of therapy of rituximab versus dexamethasone cyclophosphamide pulse (DCP) in Indian patients with PV. MATERIALS AND METHODS: It is a retrospective data analysis, from the Immunobullous disease clinic in a tertiary centre of eastern India, of management of PV. In our institute we use either rituximab or DCP for the management of moderate to severe cases of PV, depending on that we retrospectively divided the treated cases of PV in two groups. Patients who were treated with rheumatoid arthritis (RA) protocol of rituximab were considered to be group 1. Patients who were treated with DCP were included in group 2. Response was assessed by pemphigus area, and activity score (PAAS), Dermatology life quality index (DLQI); photographic documentation, and blood parameters were monitored. RESULTS: Both groups showed significant improvement in PAAS and DLQI, the improvement was faster and well sustained in the rituximab group. In terms of safety and development of new vesicles, rituximab had a better profile with only 1 patient having adverse effects and none with new vesicles as compared to DCP (3 had adverse effects and 2 developed new vesicles). CONCLUSIONS: Rituximab offers the advantage of early and prolonged remission, lesser adverse effects, better effectiveness, less risk of relapses, faster improvement of PAAS, and DLQI. Though rituximab is an expensive drug, but on evaluating the cost of whole therapy, it was seen that rituximab infusions are actually cheaper compared to DCP pulse. We suggest, rituximab can be used as the first-line of therapy for pemphigus vulgaris in the Indian context.

Haemoglobinopathies in India: estimates of blood requirements and treatment costs for the decade 2017-2026.

The Government of India is presently engaged in the implementation of a prevention and control programme for two major forms of haemoglobinopathies, thalassaemia major and sickle cell disease, with guidelines for their prevention and management formulated under the National Health Mission. Based on projections for the population up to the year 2026, the annual blood requirement for treatment will increase to 9.24 million units, together with an 86% increase in budgetary requirements which then would account for over 19% of the current National Health Budget. To avert a public health crisis there is an urgent need to fully implement the prevention programme for haemoglobinopathies.

Recent Progress in Chitosanase Production of Monomer-Free Chitooligosaccharides: Bioprocess Strategies and Future Applications.

Biological activities of chitosan oligosaccharides (COS) are well documented, and numerous reports of COS production using specific and non-specific enzymes are available. However, strategies for improving the overall yield by making it monomer free need to be developed. Continuous enzymatic production from chitosan derived from marine wastes is desirable and is cost-effective. Isolation of potential microbes showing chitosanase activity from various ecological niches, gene cloning, enzyme immobilization, and fractionation/purification of COS are some areas, where lot of work is in progress. This review covers recent measures to improve monomer-free COS production using chitosanase/non-specific enzymes and purification/fractionation of these molecules using ultrafiltration and column chromatographic techniques. Various bioprocess strategies, gene cloning for enhanced chitosanase enzyme production, and other measures for COS yield improvements have also been covered in this review. COS derivative preparation as well as COS-coated nanoparticles for efficient drug delivery are being focused in recent studies.

Enzymatic production of glucosamine and chitooligosaccharides using newly isolated exo-ß-D-glucosaminidase having transglycosylation activity.

Exochitosanase secreting fungus (A. fumigatus IIT-004) was isolated from fish waste using 1 % (w/v) chitosan as sole carbon source after multistage screening. Chitosan-dependent exochitosanase enzyme production (6 IU ml-1) in log phase of growth (chitosan utilization rate 0.11 g g-1 cell h-1) was observed for Aspergillus fumigatus in chitosan minimal salt medium and there was no enzyme production in glucose medium. Enzyme production was found to be extracellular and subjected to purification by a number of steps like acetone fractionation as well as column chromatography. 40 % yield and 26-fold of enzyme purification was achieved after all the steps. Purified enzyme was characterized for optimum temperature, pH, ionic strength and substrate specificity. The K m and V max for purified exochitosanase enzyme was calculated to be 8 mg ml-1 and 5.2 × 10-6 mol mg-1 min-1. Enzyme was immobilized on polyacrylonitrile nanofibres membrane matrix by adsorption as well as amidination. Enzymatic production of glucosamine was achieved using various chitosan substrates by free/immobilized exochitosanase and compared. Isolated and purified exochitosanase also showed transglycosylation activity.

Genotype-phenotype correlation and report of novel mutations in ß-globin gene in thalassemia patients.

Heterogeneity in thalassemia is due to various modifying factors viz. coinheritance of α-gene defects, abnormal hemoglobin, XmnI polymorphism, variation in repeat sequences present in LCR, and silencer region of the gene. The present work on populations from eastern regions of India was undertaken to study the genetic profile of heterogeneity in thalassemia patients. Mutation analysis in 126 index families revealed the presence of 3 novel mutations: CD2 (-A) in the 1st exon, -42 (C-G), and -223 (T-C) in the promoter region of ß-globin gene. The modifying effect of coexisting α-gene defects, and abnormal Hb (HbS) was clearly observed in our study, however ameliorating effect of T allele of XmnI polymorphism was not found. Analysis of the regulatory regions (LCR) exhibited new combinations (CA(15)TA(5) and CA(13)TA(8)) in HS1 region and one (AT)(10)T(3) in (AT)(x)T(y )silencer region. Thus disparate factors, when considered together, were able to explain several of the thalassemic phenotypes, otherwise not explained by the ß globin mutations. However, there were still some cases in this group whose molecular origin could not be ascertained. Our findings confirm not only the extensive genotypic and clinical heterogeneity in ß thalassemia but also the need to look for more modulators and modifiers to better understand the genotype-phenotype correlation in thalassemia.

Haemoglobinopathies in eastern Indian states: a demographic evaluation.

Haemoglobinopathies are a leading cause of child mortality worldwide, although with a variable geographical incidence. A reliable estimate of prevalence of the disease is necessary for reducing its burden. However, most studies in India are either hospital based or from certain regions of the country and hence may not realistically reflect the disease burden. The eastern Indian states of Bihar, Chhattisgarh and Jharkhand and eastern region of Uttar Pradesh, which comprise ~25 % population of the country, are poorly studied with respect to haemoglobinopathies. The present study, conducted on 1,642 individuals from this region, shows a frequency of 3.4 % for ß-thalassaemia trait (BTT), 3.4 % for sickle cell haemoglobin trait (HbS)/haemoglobin E trait (HbE) and 18 % for α-globin defects. While BTT mutations are distributed rather uniformly across the region, HbS occurs only in Chhattisgarh and Jharkhand, the regions rich in tribal populations. The frequency of α-gene mutation is strikingly high, occurring even in individuals with normal blood count, in tribal as well as non-tribal groups. The mutation spectrum of BTT is also distinct since the common mutations, IVS1-1 (G-T) and 619 bp del, are absent while CD15 (G-A) is the second most frequent. The HbA2 level in the suspected cases is strikingly low. We demonstrate association of the low HbA2 level with vitamin B12 and folate deficiency in this cohort. Thus, the present report besides providing an estimate of the carrier frequency of ß-thalassaemia traits also confirms high prevalence of α-gene defects and regional heterogeneity in distribution of HbS in the eastern parts of India.

A new bifunctional chitosanase enzyme from Streptomyces sp. and its application in production of antioxidant chitooligosaccharides.

Chitosanases produced by microbes and plants are getting attention to explore vastly available marine waste. Chitooligosaccharides and glucosamine can be produced using chitosanase enzyme and have applications in food, pharma and other industries. A potential microbial chitosanase source was found after isolation and screening of chitosan degrading microbes from garden soil. An isolate, designated as C6 produced chitosanase enzyme upon induction by chitosan substrates. Production of 6 U/ml of chitosanase enzyme was achieved from this isolate on chitosan minimal salt broth medium at 32 °C after 3 days of growth. The enzyme was able to hydrolyse both chitosan and cellulosic substrates. Enzymatic production of D -glucosamine and chitooligosaccharides were studied with various chitosan substrates using crude enzyme. The yield of glucosamine was found to be 40% after 2 h of reaction at 40 °C, and chitosan oligomers were produced having two to six polymerizations at 60 °C reaction temperature. The hydrolysates showed 50% antioxidant activity as compared to ascorbic acid.

Electrospun polyacrylonitrile nanofibrous membranes for chitosanase immobilization and its application in selective production of chitooligosaccharides.

Polyacrylonitrile nanofibrous membranes (PANNFM) were prepared by electrospinning from 10 wt.% of PAN solution and its surface was modified by amidination reaction. A new chitosan degrading enzyme from Aspergillus sp. was covalently immobilized on PANNFM. Immobilization efficiency of 80% was achieved by activating PANNFM surface for 30 min followed by 2 h treatment with enzyme solution. The optimum temperature and pH for immobilized enzyme were 50°C and 5.8, respectively. The immobilized chitosanase retained >70% activity after ten repeated batch reaction and could be stored up to 60 days at 4°C with minor loss in activity. Chitosan hydrolysis using different substrates were studied using immobilized chitosanase in batch conditions. Continuous selective production of chitooligosaccharides (dimer to hexamer) by changing the temperature was achieved by PANNFM-chitosanase.

ThalInd, a ß-thalassemia and hemoglobinopathies database for India: defining a model country-specific and disease-centric bioinformatics resource.

Web-based informatics resources for genetic disorders have evolved from genome-wide databases like OMIM and HGMD to Locus Specific databases (LSDBs) and National and Ethnic Mutation Databases (NEMDBs). However, with the increasing amenability of genetic disorders to diagnosis and better management, many previously underreported conditions are emerging as disorders of public health significance. In turn, the greater emphasis on noncommunicable disorders has generated a demand for comprehensive and relevant disease-based information from end-users, including clinicians, patients, genetic epidemiologists, health administrators and policymakers. To accommodate these demands, country-specific and disease-centric resources are required to complement the existing LSDBs and NEMDBs. Currently available preconfigured Web-based software applications can be customized for this purpose. The present article describes the formulation and construction of a Web-based informatics resource for ß-thalassemia and other hemoglobinopathies, initially for use in India, a multiethnic, multireligious country with a population approaching 1,200 million. The resource ThalInd (http://ccg.murdoch.edu.au/thalind) has been created using the LOVD system, an open source platform-independent database system. The system has been customized to incorporate and accommodate data pertinent to molecular genetics, population genetics, genotype-phenotype correlations, disease burden, and infrastructural assessment. Importantly, the resource also has been aligned with the administrative health system and demographic resources of the country.