Publications by authors named "P K S Sarma"

816 Publications

National noncommunicable disease monitoring survey (NNMS) in India: Estimating risk factor prevalence in adult population.

PLoS One 2021 2;16(3):e0246712. Epub 2021 Mar 2.

Department of Community Medicine, Maulana Azad Medical College and Associated Hospitals, New Delhi, India.

Background: The primary objective of National NCD monitoring survey (NNMS) was to generate national-level estimates of key NCD indicators identified in the national NCD monitoring framework. This paper describes survey study protocol and prevalence of risk factors among adults (18-69 years).

Materials And Methods: NNMS was a national level cross-sectional survey conducted during 2017-18. The estimated sample size was 12,000 households from 600 primary sampling units. One adult (18-69 years) per household was selected using the World Health Organization-KISH grid. The study tools were adapted from WHO-STEPwise approach to NCD risk factor surveillance, IDSP-NCD risk factor survey and WHO-Global adult tobacco survey. Total of 8/10 indicators of adult NCD risk factors according to national NCD disease monitoring framework was studied. This survey for the first time estimated dietary intake of salt intake of population at a national level from spot urine samples.

Results: Total of 11139 households and 10659 adults completed the survey. Prevalence of tobacco and alcohol use was 32.8% (95% CI: 30.8-35.0) and 15.9% (95% CI: 14.2-17.7) respectively. More than one-third adults were physically inactive [41.3% (95% CI: 39.4-43.3)], majority [98.4% (95% CI: 97.8-98.8)] consumed less than 5 servings of fruits and / or vegetables per day and mean salt intake was 8 g/day (95% CI: 7.8-8.2). Proportion with raised blood pressure and raised blood glucose were 28.5% (95% CI: 27.0-30.1) and 9.3% (95% CI: 8.3-10.5) respectively. 12.8% (95% CI: 11.2-14.5) of adults (40-69 years) had ten-year CVD risk of ≥30% or with existing CVD.

Conclusion: NNMS was the first comprehensive national survey providing relevant data to assess India's progress towards targets in National NCD monitoring framework and NCD Action Plan. Established methodology and findings from survey would contribute to plan future state-based surveys and also frame policies for prevention and control of NCDs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246712PLOS
March 2021

Clinically relevant cell culture models and their significance in isolation, pathogenesis, vaccine development, repurposing and screening of new drugs for SARS-CoV-2: a systematic review.

Tissue Cell 2021 Jan 26;70:101497. Epub 2021 Jan 26.

Department of Pharmacology, PGIMER, Chandigarh, India. Electronic address:

Background: In-Vitro/Cellular evidence is the backbone and vital proof of concept during the development of novel therapeutics as well as drugs repurposing against COVID-19. Choosing an ideal in-vitro model is vital as the virus entry is through ACE2, CD147, and TMPRSS2 dependant and very specific. In this regard, this is the first systematic review addressing the importance of specific cell lines used as potential in-vitro models in the isolation, pathogenesis, and therapeutics for SARS-COV-2.

Methods: We searched 17 literature databases with appropriate keywords, and identified 1173 non-duplicate studies. In the present study, 71 articles are included after a careful, thorough screening of the titles and their abstracts for possible inclusion using predefined inclusion/exclusion criteria (PRISMA Guidelines).

Results: In the current study, we compiled cell culture-based studies for SARS-CoV-2 and found the best compatible In-Vitro models for SARS-CoV-2 (Vero, VeroE6, HEK293 as well as its variants, Huh-7, Calu-3 2B4, and Caco2). Among other essential cell lines used include LLC-MK2, MDCKII, BHK-21, HepG2, A549,T cell leukemia (MT-2), stems cells based cell line DYR0100for differentiation assays, and embryo-specific NIH3T3 cell line for vaccine production.

Conclusion: The Present study provides a detailed summary of all the drugs/compounds screened for drug repurposing and discovery purpose using the in-vitro models for SARS-CoV-2 along with isolation, pathogenesis and vaccine production. This study also suggests that after careful evaluation of all the cell line based studies, Kidney cells (VeroE6, HEK293 along with their clones), liver Huh-7cells, respiratory Calu-3 cells, and intestinal Caco-2 are the most widely used in-vitro models for SARS-CoV-2.
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http://dx.doi.org/10.1016/j.tice.2021.101497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836970PMC
January 2021

Life Style and Behavioural Factors are Associated with Stroke Recurrence Among Survivors of First Episode of Stroke: A Case Control Study.

J Stroke Cerebrovasc Dis 2021 Feb 3;30(4):105606. Epub 2021 Feb 3.

Ex- Professor, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Honorary Chairman, Health Action by People, Trivandrum 695011 INDIA.

Background: Secondary stroke prevention treatment is associated with an 80% reduction in risk of recurrent stroke. But one out of every four strokes are recurrent. Adherence to pharmacological therapy and strict control of risk factors are essential for prevention of recurrent strokes.

Methods: Pair matched incident case control study was done to find out the factors associated with stroke recurrence after first ever stroke. Incident cases of recurrent strokes and age and post stroke period matched controls were recruited prospectively. The estimated sample size for the study was 70 matched pairs. Data collected from medical records and by visiting their homes. Analysis was done using R statistical software.

Results: Bivariate analysis showed cardio embolic stroke subtype, poor lipid control, unhealthy diet, physical inactivity, medication nonadherence, presence of depression, memory problems no discharge advice at index admission and low income were associated increased risk of recurrence. Higher mean NIHSS score and a greater number of days of hospitalisation during index stroke had less risk of recurrence. Conditional logistic regression analysis revealed non adherence to medication (OR 7.46, 1.67-33.28) and not receiving discharge advice at index admission (OR 10.79, 2.38-49.02) were associated with increased risk of recurrence whereas lacunar stroke (OR 0.08, 0.01-0.59) and a greater number of days of hospitalization during index stroke (OR 0.82, 0.67-0.99) were associated with less risk of recurrence.

Conclusion: Individualised patient education regarding stroke, recurrence risk, medication adherence, healthy lifestyle and risk factor control can reduce stroke recurrence risk.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105606DOI Listing
February 2021

Stem cell therapy in COVID-19: Pooled evidence from SARS-CoV-2, SARS-CoV, MERS-CoV and ARDS: A systematic review.

Biomed Pharmacother 2021 Jan 28;137:111300. Epub 2021 Jan 28.

Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. Electronic address:

Background: SARS-CoV-2, which majorly affects the lungs and respiratory tract is thought due to dysregulation of the immune system which causes an immense imbalance of the cytokines. However, till now no standard treatment has been developed in treating the disease. On the other hand, it becomes important to prevent the acute respiratory tract infection due to COVID-19 which is the most dangerous phase leading to increased mortality. Hence this systematic review has been framed by pooling the available data of the use of stem cells in SARS-CoV-2, SARS-CoV, MERS-CoV and ARDS.

Methods: 6 literature databases (PubMed, EMBASE, Scopus, Google Scholar, Clinicaltrials.gov, and Clinical trial registry of India) were searched for relevant studies till 10th August 2020 using keywords stem cells, mesenchymal stem cells, cell therapy, SARS CoV-2, SARS Coronavirus, Coronavirus 2, COVID-19, nCoV-19, Novel Coronavirus, MERS CoV, ARDS, acute respiratory distress syndrome.

Results: The observations of this systematic review suggest capability of MSCs in reducing the systemic inflammation and protecting against SARS-CoV-2 as evidenced by the available clinical data.

Conclusion: MSCs can overcome the clinical challenges currently faced by SARS-CoV-2 infected patients, specifically who are seriously ill and not responding to conventional therapies. Though the available clinical data is motivating, still predicting the therapeutic potential of MSCs will be too early in COVID-19. Hence, further studies in a larger cohort of patients becomes a prerequisite to validate their potential efficacy.
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http://dx.doi.org/10.1016/j.biopha.2021.111300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843034PMC
January 2021

Engineering of Exciton-Plasmon Coupling Using 2D-WS Nanosheets for 1000-Fold Fluorescence Enhancement in Surface Plasmon-Coupled Emission Platforms.

Langmuir 2021 Feb 25;37(5):1954-1960. Epub 2021 Jan 25.

STAR Laboratory, Department of Chemistry, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, Puttaparthi, Anantapur, Andhra Pradesh 515134, India.

Enhancement of fluorescence emission from single-photon quantum emitters on plasmonic nanomaterials using surface plasmon-coupled emission (SPCE) platforms has seen significant advancements. In parallel, there has also been an exponential rise in applications involving two-dimensional (2D) transition-metal dichalcogenides (TMDs) that exhibit unique exciton-plasmon interactions. Although both these Frontier research areas have impacted the development of sensor and sensing technologies, no study coalesces these two arenas for translational applications. In this work, we use thin WS nanosheets for realizing 1000-fold fluorescence enhancement on the SPCE platform. Structure-dependent fluorescence enhancement exhibited by WS provides new insight into the use of TMDs and exciton-plasmon coupling in SPCE substrates. Cellphone-based detection of the emitting dipole is another unique aspect of this work that presents a low-cost alternative in comparison with high-end detectors.
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http://dx.doi.org/10.1021/acs.langmuir.0c03465DOI Listing
February 2021

Mutations and structural variations in Catechol-O-methyltransferase gene of patients exhibiting chronic persistent surgical pain.

Rev Esp Anestesiol Reanim 2021 Mar 19;68(3):128-136. Epub 2021 Jan 19.

Departamento de Cirugía Cardiotorácica y Vascular, Instituto de Ciencias Médicas Sri Venkateswara, Tirupati, India.

Objectives: Mutations in the exon 4 of the COMT gene are associated with chronic persistent surgical pain (CPSP). Especially COMT mutated allele G472A (Val158Met) associated with CPSP patients is reported in different ethnic population. The purpose of this study is to evaluate the prevalence of genetic mutations and structural variations in exon 4 of COMT that can be related to the appearance of CPSP in patients under sternotomy.

Materials And Methods: One hundred patients with American Society of Anesthesiologists (ASA) physical status grades i, ii and iii, who underwent sternotomy procedures, were selected to assess the development and magnitude of the CPSP evaluated with pain questionaries' at the end of three months after surgery. This was correlated with COMT allele presence. The exon 4 of COMT gene (that contains the G472A allele) was studied. The polymerase chain reaction (PCR) products were sequenced and mutated sequences were deposited in GenBank®. The structural analysis of COMT was performed using ProCheck® and distortions of three-dimensional tertiary structural orientation was evaluated with root-mean-square deviation (RMSD) score.

Results: Genetic analysis carried out through PCR showed 220 bp amplicons. The 25% of patients with CPSP showed a Numeric Rating Scale (NRS) > 4 pain score. The 20% of these patients have known Val158Met mutation, 5% of patients showed novel mutations c.382C>G, c.383G>C, p.(Arg128Ala). The mutations in COMT gene contributed major structural variations in COMT leading to the formation of inactive COMT that correlates with CPSP.

Conclusion: The results of the present study showed that both novel and previously reported mutations in COMT gene has strong association with CPSP.
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http://dx.doi.org/10.1016/j.redar.2020.09.012DOI Listing
March 2021

docking and comparative ADMET profile of different glycogen synthase kinase 3 beta inhibitors as the potential leads for the development of anti-Alzheimer drug therapy.

J Adv Pharm Technol Res 2020 Oct-Dec;11(4):194-201. Epub 2020 Oct 10.

Department of Pharmacology, PGIMER, Chandigarh, India.

Glycogen synthase kinase 3 beta (GSK3 β) plays a key role in pathologic hyper phosphorylation of tau and plays an important role in the pathogenesis of Alzheimer's disease. In the present study, we have screened a set of potential hits in platform to gain insight regarding binding profile with the target (GSK3 β) from molecular docking, ADME/T, and molecular dynamics (MD) simulations. The three screened compounds 6-BIBEO, 6-BIO, and SB216763 topped the docking score chart when subjected to hard scoring function extraprecision of GLIDE. The active site dynamics study through MD simulations provides insights on residues Asp133, Val135, and Ile62 which are in a state of minimum deviation from their mean special position while they interact with the respective ligands. The same molecules also displayed favorable pharmacokinetic profile, negative Ames test and falls correctly within drug-likeliness rules. These agents can be taken forward further for the development of anti-Alzheimer's drug therapy.
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http://dx.doi.org/10.4103/japtr.JAPTR_178_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784934PMC
October 2020

Ivermectin as a potential drug for treatment of COVID-19: an in-sync review with clinical and computational attributes.

Pharmacol Rep 2021 Jan 3. Epub 2021 Jan 3.

Department of Pharmacology, Post Graduate Institute of Medical Education and Reseasrch (PGIMER), Chandigarh, 160012, India.

Introduction: COVID-19 cases are on surge; however, there is no efficient treatment or vaccine that can be used for its management. Numerous clinical trials are being reviewed for use of different drugs, biologics, and vaccines in COVID-19. A much empirical approach will be to repurpose existing drugs for which pharmacokinetic and safety data are available, because this will facilitate the process of drug development. The article discusses the evidence available for the use of Ivermectin, an anti-parasitic drug with antiviral properties, in COVID-19.

Methods: A rational review of the drugs was carried out utilizing their clinically significant attributes. A more thorough understanding was met by virtual embodiment of the drug structure and realizable viral targets using artificial intelligence (AI)-based and molecular dynamics (MD)-simulation-based study.

Conclusion: Certain studies have highlighted the significance of ivermectin in COVID-19; however, it requires evidences from more Randomised Controlled Trials (RCTs) and dose- response studies to support its use. In silico-based analysis of ivermectin's molecular interaction specificity using AI and classical mechanics simulation-based methods indicates positive interaction of ivermectin with viral protein targets, which is leading for SARS-CoV 2 N-protein NTD (nucleocapsid protein N-terminal domain).
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http://dx.doi.org/10.1007/s43440-020-00195-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778723PMC
January 2021

Comments on: Intraoperative injection versus sponge-applied mitomycin C during trabeculectomy: One-year study.

Indian J Ophthalmol 2021 01;69(1):178-179

Sri Sankaradeva Nethralaya, Guwahati, Assam, India.

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http://dx.doi.org/10.4103/ijo.IJO_967_20DOI Listing
January 2021

Tuning the transition barrier of H dissociation in the hydrogenation of CO to formic acid on Ti-doped SnO clusters.

Phys Chem Chem Phys 2021 Jan;23(1):204-210

Department of Chemical Sciences, Tezpur University, Tezpur, Assam, India.

A density functional theory study has been performed to investigate cation-doped Sn2O4 clusters for selective catalytic reduction of CO2. We study the influence of Si and Ti dopants on the height of the H2 dissociation barrier for the doped systems, and then the subsequent mechanism for the conversion of CO2 into formic acid (FA) via a hydride pinning pathway. The lowest barrier height for H2 dissociation is observed across the 'Ti-O' bond of the Ti-doped Sn2O4 cluster, with a negatively charged hydride (Ti-H) formed during the heterolytic H2 dissociation, bringing selectivity towards the desired FA product. The formation of a formate intermediate is identified as the rate-determining step (RDS) for the whole pathway, but the barrier height is substantially reduced for the Ti-doped system when compared to the same steps on the undoped Sn2O4 cluster. The free energy of formate formation in the RDS is calculated to be negative, which reveals that the hydride transfer would occur spontaneously. Overall, our results show that the small-sized Ti-doped Sn2O4 clusters exhibit better catalytic activity than undoped clusters in the important process of reducing CO2 to FA when proceeding via the hydride pinning pathway.
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http://dx.doi.org/10.1039/d0cp04472eDOI Listing
January 2021

Emerging role of artificial intelligence in therapeutics for COVID-19: a systematic review.

J Biomol Struct Dyn 2020 Dec 10:1-16. Epub 2020 Dec 10.

Department of Biochemistry, All India Institute of Medical Sciences, Rishikesh, India.

To elucidate the role of artificial intelligence (AI) in therapeutics for coronavirus disease 2019 (COVID-19). Five databases were searched (December 2019-May 2020). We included both published and pre-print original articles in English that applied AI, machine learning or deep learning in drug repurposing, novel drug discovery, vaccine and antibody development for COVID-19. Out of 31 studies included, 16 studies applied AI for drug repurposing, whereas 10 studies utilized AI for novel drug discovery. Only four studies used AI technology for vaccine development, whereas one study generated stable antibodies against SARS-CoV-2. Approx. 50% of studies exclusively targeted 3CLpro of SARS-CoV-2, and only two studies targeted ACE/TMPSS2 for inhibiting host viral interactions. Around 16% of the identified drugs are in different phases of clinical evaluation against COVID-19. AI has emerged as a promising solution of COVID-19 therapeutics. During this current pandemic, many of the researchers have used AI-based strategies to process large databases in a more customized manner leading to the faster identification of several potential targets, novel/repurposing of drugs and vaccine candidates. A number of these drugs are either approved or are in a late-stage clinical trial and are potentially effective against SARS-CoV2 indicating validity of the methodology. However, as the use of AI-based screening program is currently in budding stage, sole reliance on such algorithms is not advisable at this current point of time and an evidence based approach is warranted to confirm their usefulness against this life-threatening disease. Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1855250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738208PMC
December 2020

Strengthening policy coding methodologies to improve COVID-19 disease modeling and policy responses: a proposed coding framework and recommendations.

BMC Med Res Methodol 2020 12 8;20(1):298. Epub 2020 Dec 8.

University of Washington School of Public Health, Seattle, WA, USA.

Background: In recent months, multiple efforts have sought to characterize COVID-19 social distancing policy responses. These efforts have used various coding frameworks, but many have relied on coding methodologies that may not adequately describe the gradient in social distancing policies as states "re-open."

Methods: We developed a COVID-19 social distancing intensity framework that is sufficiently specific and sensitive to capture this gradient. Based on a review of policies from a 12 U.S. state sample, we developed a social distancing intensity framework consisting of 16 domains and intensity scales of 0-5 for each domain.

Results: We found that the states with the highest average daily intensity from our sample were Pennsylvania, Washington, Colorado, California, and New Jersey, with Georgia, Florida, Massachusetts, and Texas having the lowest. While some domains (such as restaurants and movie theaters) showed bimodal policy intensity distributions compatible with binary (yes/no) coding, others (such as childcare and religious gatherings) showed broader variability that would be missed without more granular coding.

Conclusion: This detailed intensity framework reveals the granularity and nuance between social distancing policy responses. Developing standardized approaches for constructing policy taxonomies and coding processes may facilitate more rigorous policy analysis and improve disease modeling efforts.
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http://dx.doi.org/10.1186/s12874-020-01174-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721792PMC
December 2020

Systematic review and meta-analysis of effectiveness and safety of favipiravir in the management of novel coronavirus (COVID-19) patients.

Indian J Pharmacol 2020 Sep-Oct;52(5):414-421

Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Multiple options are being tried for the management of 2019-nCoV infection since its pandemic started. Favipiravir (FPV) is one of drugs, which is also being tried for the management of 2019-nCoV infection. The present study aimed to evaluate the efficacy and safety of FPV in published literature. Comparative randomized or nonrandomized controlled clinical trials comparing FPV to the standard of care (SOC)/control or other antiviral agent/combinations were included. A total of 12 databases were searched and identify four studies which were further used for final analysis. The data analysis was done as pooled prevalence using a random effect model by "RevMan manager version 5.4.1 and "R" software. The point estimate, odds ratio (OR) with 95% confidence interval (CI) was calculated for dichotomous data. In the present study, the marginal beneficial effect was seen in the FPV group in overall clinical improvement comparison to SOC/control, i.e., (4 studies, log OR [95% CI] (-0.19 [-0.51, 0.13]). However, in all other outcomes, it was found to be comparable to the SOC/control arm namely "clinical improvement on day 7-10" (3 studies, OR [95% CI] 1.63 [1.07, 2.48]) while "clinical improvement on day 10-14" (3 studies, OR [95% CI] 1.37 [0.24, 7.82]) and viral negativity was seen (4 studies, OR [95% CI] 1.91 [0.91, 4.01]). No difference in efficacy was found between FPV versus lopinavir/ritonavir or arbidol groups. Regarding adverse effects, except for the occurrence of rash (higher in the FPV group), safety was comparable to SOC. In our study, there was a marginal difference between the FPV and the SOC arm in terms of "clinical improvement" on day 7-10 or 10-14, and "virological negativity" on day 10-14." However, some benefit was observed in a few studies, but it was also comparable to the control drugs or SOC.
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http://dx.doi.org/10.4103/ijp.ijp_998_20DOI Listing
December 2020

Variation in biosynthesis of an effective anticancer secondary metabolite, mahanine in Murraya koenigii, conditional on soil physicochemistry and weather suitability.

Sci Rep 2020 11 18;10(1):20096. Epub 2020 Nov 18.

Drug Discovery Laboratory, Life Sciences Division, Institute of Advanced Study in Science and Technology, Vigyan Path, Paschim Boragaon, Guwahati, Assam, 781035, India.

Murraya koenigii (MK) leaf being a rich source of bioactive secondary metabolites has received inordinate attention in drug development research. Formation of secondary plant metabolite(s) in medicinal plants depends on several factors and in this study the cause of variation in bioavailability and content of a vital bioactive phytochemical, mahanine in the MK leaves from different geographical locations of varying soil properties and weather parameters was determined. Accordingly, MK leaves and soil samples around the plant base in quintuplicate from each site across five states of India at similar time point were collected. Mahanine content was determined and compared among samples from different regions. The quantitative analysis data comprised that MK-leaves of southern part of India contains highest amount of mahanine, which is 16.9 times higher than that of MK-leaves of north-eastern part of India (which measured as the lowest). The results suggested that pH, conductivity and bacterial populations of the soil samples were positively correlated with mahanine content in the MK-leaves. For examples, the average soil pH of the southern India sites was in basic range (8.8 ± 0.6); whereas that of the north-east India sites was in slightly acidic ranges (6.1 ± 0.5) and mean soil conductivity value for the north east India soils was 78.3 ± 16.3 µS/cm against mean value of 432.4 ± 204.5 µs/cm for south India soils. In conclusion, this study proclaims that higher level of bioactive phytochemical, mahanine in MK leaves depending upon geographical location, weather suitability and soil's physiochemical and microbial parameters of its cultivation sites.
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http://dx.doi.org/10.1038/s41598-020-77113-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675983PMC
November 2020

Control of hypertension among teachers in schools in Kerala (CHATS-K), India.

Indian Heart J 2020 Sep - Oct;72(5):416-420. Epub 2020 Jun 27.

Department of Public Health and Community Medicine, Central University Kerala, Kasaragod, Tejaswini Hills, Periye, 671320, Kerala, India.

Objective: We investigated the prevalence, awareness, treatment, control of hypertension and the factors associated with hypertension prevalence and control among school teachers in Kerala, India.

Methods: We surveyed 2216 school teachers in Thiruvananthapuram district of Kerala as part of the control of hypertension among teachers in schools in Kerala (CHATS-K), India. We used World Health Organization STEPS tools for non-communicable diseases risk factor surveillance. Blood pressure, weight and height were measured using standard protocols. Hypertension was defined as systolic blood pressure (SBP) ≥ 140 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg, or self-reported current antihypertensive medication. Controlled hypertension was defined as SBP<140 and DBP<90 mmHg. Separate multivariate analysis was done for finding the associated factors with prevalence and control of hypertension.

Results: Age adjusted hypertension prevalence was 14.6%. Men, those with self-reported diabetes, having family history of hypertension and overweight were more likely to have higher prevalence of hypertension compared to their counterparts. Among hypertensives 62% were aware, 49% on treatment and 34% achieved adequate control. Hypertension control was significantly higher among women, diabetics and overweight individuals compared to their counterparts.

Conclusions: A higher level of hypertension control among school teachers in this study indicates an attainable level of hypertension control in the general population of the state. Teachers, with their highly regarded place in the social construct of the country and the state, could thus be used as role models for hypertension control for the general population in the state.
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http://dx.doi.org/10.1016/j.ihj.2020.06.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670257PMC
June 2020

Profile of distress callers and service utilisation of tele-counselling among the population of Assam, India: an exploratory study during COVID-19.

Open J Psychiatry Allied Sci 2021 Jan-Jun;12(1):7-12

Department of Psychiatry, Sikkim Manipal Institute of Medical Sciences, Sikkim Manipal University, Gangtok, Sikkim, India.

Background: The coronavirus disease 2019 (COVID-19) pandemic has affected people globally by causing psychological, social, and economic chaos. The Assam Police, India started telephone helplines to address the psychological issues.

Aims: To evaluate the sociodemographic profile of the distress callers, their psychosocial concerns, the interventions provided by the service provider, and whether the service users were satisfied with the intervention(s) or not.

Method: It was a cross-sectional study done during the period of lockdown (7-24 April 2020). All the callers who called the helpline were screened for anxiety, depression, suicidal thoughts (when required), and the psychosocial issues which they were facing were explored. They were provided the psychological intervention(s) at the appropriate time, and they were asked to rate their experience at the end.

Results: A total of 239 callers used the tele-counselling services. The majority of callers were male (79.1%). Most of the callers were between 19-35 years of age group (66.5%), married (52.5%), and graduates (31%). Two-thirds of the callers called to seek guidance for their own issues and one-third for their relatives or friends. Callers had anxiety (46%), depressive disorder (8.3%), and depressive symptoms not qualifying for depressive disorder (14%), and suicidal thoughts (5.44%). The commonest intervention provided to the callers was supportive (77.8%), followed by psychoeducation (30.5%), cognitive behaviour therapy (24.7%), relaxation (23.6%) and behaviour therapy (13.4%). Most of the callers utilised more than one type of therapy. Overall, most of the callers were satisfied and appreciated the tele-counselling services.

Conclusion: The findings could help in formulating psychological interventions to improve the mental health of vulnerable groups in the post-COVID-19 period to reduce psychiatric morbidity and mortality.
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http://dx.doi.org/10.5958/2394-2061.2021.00001.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644027PMC
November 2020

Comment on: Pattern Electroretinograms in Preperimetric and Perimetric Glaucoma.

Am J Ophthalmol 2021 01 31;221:325. Epub 2020 Oct 31.

Guwahati, Assam, India.

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http://dx.doi.org/10.1016/j.ajo.2020.07.040DOI Listing
January 2021

Staphylococcus aureus grown in anaerobic conditions exhibit elevated glutamine biosynthesis and biofilm units.

Can J Microbiol 2020 Nov 2. Epub 2020 Nov 2.

Sri Venkateswara Institute of Medical Sciences and University, Biotechnology, SVIMS university, Alipiri road, Tirupati, tirupati, Andhra Pradesh, India, 517507;

The enormous spread of Staphylococcus aureus infections through biofilms is a major concern in hospital-acquired infections. Biofilm formation by S. aureus on any surface is facilitated by adjusting its redox status. This organism is a facultative anaerobe shifts more towards reductive conditions by enhancing nitrogen metabolism where Glutamine synthesis plays a key role. Glutamine is synthesized by Glutamine synthetase (GS) encoded by the glnA gene was PCR amplified from the chromosomal DNA of Staphylococcus aureus, sequenced (HQ329146.1) and cloned; the pure recombinant GS exhibited KM11.06±0.05mM for Glutamate and 2.4±0.03mM for ATP. The glnA gene sequence showed high degree variability with the human counterpart while it was highly conserved in bacteria. Structural analysis revealed the GS structure of S. aureus showed close homology with other Gram-positive bacteria and exhibited a high degree of variation with E .coli GS. In the present study, we have observed the increased presence of glutamine synthetase activity in multidrug-resistant strains of Staphylococcus aureus with elevated biofilm units grown in brain heart infusion broth among them methicillin-resistant strains of S. aureus LMV3-5 showed higher biofilm units. All these results explain the important role of glutamine biosynthesis with elevated biofilm units in the pathogenesis of S. aureus.
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http://dx.doi.org/10.1139/cjm-2020-0434DOI Listing
November 2020

Measurement of the Low-Energy Antideuteron Inelastic Cross Section.

Authors:
S Acharya D Adamová A Adler J Adolfsson M M Aggarwal G Aglieri Rinella M Agnello N Agrawal Z Ahammed S Ahmad S U Ahn Z Akbar A Akindinov M Al-Turany S N Alam D S D Albuquerque D Aleksandrov B Alessandro H M Alfanda R Alfaro Molina B Ali Y Ali A Alici N Alizadehvandchali A Alkin J Alme T Alt L Altenkamper I Altsybeev M N Anaam C Andrei D Andreou A Andronic M Angeletti V Anguelov C Anson T Antičić F Antinori P Antonioli N Apadula L Aphecetche H Appelshäuser S Arcelli R Arnaldi M Arratia I C Arsene M Arslandok A Augustinus R Averbeck S Aziz M D Azmi A Badalà Y W Baek S Bagnasco X Bai R Bailhache R Bala A Balbino A Baldisseri M Ball S Balouza D Banerjee R Barbera L Barioglio G G Barnaföldi L S Barnby V Barret P Bartalini C Bartels K Barth E Bartsch F Baruffaldi N Bastid S Basu G Batigne B Batyunya D Bauri J L Bazo Alba I G Bearden C Beattie C Bedda N K Behera I Belikov A D C Bell Hechavarria F Bellini R Bellwied V Belyaev G Bencedi S Beole A Bercuci Y Berdnikov D Berenyi R A Bertens D Berzano M G Besoiu L Betev A Bhasin I R Bhat M A Bhat H Bhatt B Bhattacharjee A Bianchi L Bianchi N Bianchi J Bielčík J Bielčíková A Bilandzic G Biro R Biswas S Biswas J T Blair D Blau C Blume G Boca F Bock A Bogdanov S Boi J Bok L Boldizsár A Bolozdynya M Bombara G Bonomi H Borel A Borissov H Bossi E Botta L Bratrud P Braun-Munzinger M Bregant M Broz E Bruna G E Bruno M D Buckland D Budnikov H Buesching S Bufalino O Bugnon P Buhler P Buncic Z Buthelezi J B Butt S A Bysiak D Caffarri A Caliva E Calvo Villar J M M Camacho R S Camacho P Camerini F D M Canedo A A Capon F Carnesecchi R Caron J Castillo Castellanos A J Castro E A R Casula F Catalano C Ceballos Sanchez P Chakraborty S Chandra W Chang S Chapeland M Chartier S Chattopadhyay S Chattopadhyay A Chauvin C Cheshkov B Cheynis V Chibante Barroso D D Chinellato S Cho P Chochula T Chowdhury P Christakoglou C H Christensen P Christiansen T Chujo C Cicalo L Cifarelli L D Cilladi F Cindolo M R Ciupek G Clai J Cleymans F Colamaria D Colella A Collu M Colocci M Concas G Conesa Balbastre Z Conesa Del Valle G Contin J G Contreras T M Cormier Y Corrales Morales P Cortese M R Cosentino F Costa S Costanza P Crochet E Cuautle P Cui L Cunqueiro D Dabrowski T Dahms A Dainese F P A Damas M C Danisch A Danu D Das I Das P Das P Das S Das A Dash S Dash S De A De Caro G de Cataldo J de Cuveland A De Falco D De Gruttola N De Marco S De Pasquale S Deb H F Degenhardt K R Deja A Deloff S Delsanto W Deng P Dhankher D Di Bari A Di Mauro R A Diaz T Dietel P Dillenseger Y Ding R Divià D U Dixit Ø Djuvsland U Dmitrieva A Dobrin B Dönigus O Dordic A K Dubey A Dubla S Dudi M Dukhishyam P Dupieux R J Ehlers V N Eikeland D Elia B Erazmus F Erhardt A Erokhin M R Ersdal B Espagnon G Eulisse D Evans S Evdokimov L Fabbietti M Faggin J Faivre F Fan A Fantoni M Fasel P Fecchio A Feliciello G Feofilov A Fernández Téllez A Ferrero A Ferretti A Festanti V J G Feuillard J Figiel S Filchagin D Finogeev F M Fionda G Fiorenza F Flor A N Flores S Foertsch P Foka S Fokin E Fragiacomo U Frankenfeld U Fuchs C Furget A Furs M Fusco Girard J J Gaardhøje M Gagliardi A M Gago A Gal C D Galvan P Ganoti C Garabatos J R A Garcia E Garcia-Solis K Garg C Gargiulo A Garibli K Garner P Gasik E F Gauger M B Gay Ducati M Germain J Ghosh P Ghosh S K Ghosh M Giacalone P Gianotti P Giubellino P Giubilato A M C Glaenzer P Glässel A Gomez Ramirez V Gonzalez L H González-Trueba S Gorbunov L Görlich A Goswami S Gotovac V Grabski L K Graczykowski K L Graham L Greiner A Grelli C Grigoras V Grigoriev A Grigoryan S Grigoryan O S Groettvik F Grosa J F Grosse-Oetringhaus R Grosso R Guernane M Guittiere K Gulbrandsen T Gunji A Gupta R Gupta I B Guzman R Haake M K Habib C Hadjidakis H Hamagaki G Hamar M Hamid R Hannigan M R Haque A Harlenderova J W Harris A Harton J A Hasenbichler H Hassan Q U Hassan D Hatzifotiadou P Hauer L B Havener S Hayashi S T Heckel E Hellbär H Helstrup A Herghelegiu T Herman E G Hernandez G Herrera Corral F Herrmann K F Hetland H Hillemanns C Hills B Hippolyte B Hohlweger J Honermann D Horak A Hornung S Hornung R Hosokawa P Hristov C Huang C Hughes P Huhn T J Humanic H Hushnud L A Husova N Hussain S A Hussain D Hutter J P Iddon R Ilkaev H Ilyas M Inaba G M Innocenti M Ippolitov A Isakov M S Islam M Ivanov V Ivanov V Izucheev B Jacak N Jacazio P M Jacobs S Jadlovska J Jadlovsky S Jaelani C Jahnke M J Jakubowska M A Janik T Janson M Jercic O Jevons M Jin F Jonas P G Jones J Jung M Jung A Jusko P Kalinak A Kalweit V Kaplin S Kar A Karasu Uysal D Karatovic O Karavichev T Karavicheva P Karczmarczyk E Karpechev A Kazantsev U Kebschull R Keidel M Keil B Ketzer Z Khabanova A M Khan S Khan A Khanzadeev Y Kharlov A Khatun A Khuntia B Kileng B Kim B Kim D Kim D J Kim E J Kim H Kim J Kim J S Kim J Kim J Kim J Kim M Kim S Kim T Kim T Kim S Kirsch I Kisel S Kiselev A Kisiel J L Klay C Klein J Klein S Klein C Klein-Bösing M Kleiner A Kluge M L Knichel A G Knospe C Kobdaj M K Köhler T Kollegger A Kondratyev N Kondratyeva E Kondratyuk J Konig S A Konigstorfer P J Konopka G Kornakov L Koska O Kovalenko V Kovalenko M Kowalski I Králik A Kravčáková L Kreis M Krivda F Krizek K Krizkova Gajdosova M Krüger E Kryshen M Krzewicki A M Kubera V Kučera C Kuhn P G Kuijer L Kumar S Kundu P Kurashvili A Kurepin A B Kurepin A Kuryakin S Kushpil J Kvapil M J Kweon J Y Kwon Y Kwon S L La Pointe P La Rocca Y S Lai M Lamanna R Langoy K Lapidus A Lardeux P Larionov E Laudi R Lavicka T Lazareva R Lea L Leardini J Lee S Lee S Lehner J Lehrbach R C Lemmon I León Monzón E D Lesser M Lettrich P Lévai X Li X L Li J Lien R Lietava B Lim V Lindenstruth A Lindner C Lippmann M A Lisa A Liu J Liu S Liu W J Llope I M Lofnes V Loginov C Loizides P Loncar J A Lopez X Lopez E López Torres J R Luhder M Lunardon G Luparello Y G Ma A Maevskaya M Mager S M Mahmood T Mahmoud A Maire R D Majka M Malaev Q W Malik L Malinina D Mal'Kevich P Malzacher G Mandaglio V Manko F Manso V Manzari Y Mao M Marchisone J Mareš G V Margagliotti A Margotti A Marín C Markert M Marquard C D Martin N A Martin P Martinengo J L Martinez M I Martínez G Martínez García S Masciocchi M Masera A Masoni L Massacrier E Masson A Mastroserio A M Mathis O Matonoha P F T Matuoka A Matyja C Mayer F Mazzaschi M Mazzilli M A Mazzoni A F Mechler F Meddi Y Melikyan A Menchaca-Rocha C Mengke E Meninno A S Menon M Meres S Mhlanga Y Miake L Micheletti L C Migliorin D L Mihaylov K Mikhaylov A N Mishra D Miśkowiec A Modak N Mohammadi A P Mohanty B Mohanty M Mohisin Khan Z Moravcova C Mordasini D A Moreira De Godoy L A P Moreno I Morozov A Morsch T Mrnjavac V Muccifora E Mudnic D Mühlheim S Muhuri J D Mulligan A Mulliri M G Munhoz R H Munzer H Murakami S Murray L Musa J Musinsky C J Myers J W Myrcha B Naik R Nair B K Nandi R Nania E Nappi M U Naru A F Nassirpour C Nattrass R Nayak T K Nayak S Nazarenko A Neagu R A Negrao De Oliveira L Nellen S V Nesbo G Neskovic D Nesterov L T Neumann B S Nielsen S Nikolaev S Nikulin V Nikulin F Noferini P Nomokonov J Norman N Novitzky P Nowakowski A Nyanin J Nystrand M Ogino A Ohlson J Oleniacz A C Oliveira Da Silva M H Oliver C Oppedisano A Ortiz Velasquez A Oskarsson J Otwinowski K Oyama Y Pachmayer V Pacik S Padhan D Pagano G Paić J Pan S Panebianco P Pareek J Park J E Parkkila S Parmar S P Pathak B Paul J Pazzini H Pei T Peitzmann X Peng L G Pereira H Pereira Da Costa D Peresunko G M Perez S Perrin Y Pestov V Petráček M Petrovici R P Pezzi S Piano M Pikna P Pillot O Pinazza L Pinsky C Pinto S Pisano D Pistone M Płoskoń M Planinic F Pliquett M G Poghosyan B Polichtchouk N Poljak A Pop S Porteboeuf-Houssais V Pozdniakov S K Prasad R Preghenella F Prino C A Pruneau I Pshenichnov M Puccio J Putschke S Qiu L Quaglia R E Quishpe S Ragoni S Raha S Rajput J Rak A Rakotozafindrabe L Ramello F Rami S A R Ramirez R Raniwala S Raniwala S S Räsänen R Rath V Ratza I Ravasenga K F Read A R Redelbach K Redlich A Rehman P Reichelt F Reidt X Ren R Renfordt Z Rescakova K Reygers A Riabov V Riabov T Richert M Richter P Riedler W Riegler F Riggi C Ristea S P Rode M Rodríguez Cahuantzi K Røed R Rogalev E Rogochaya D Rohr D Röhrich P F Rojas P S Rokita F Ronchetti A Rosano E D Rosas K Roslon A Rossi A Rotondi A Roy P Roy O V Rueda R Rui B Rumyantsev A Rustamov E Ryabinkin Y Ryabov A Rybicki H Rytkonen O A M Saarimaki R Sadek S Sadhu S Sadovsky K Šafařík S K Saha B Sahoo P Sahoo R Sahoo S Sahoo P K Sahu J Saini S Sakai S Sambyal V Samsonov D Sarkar N Sarkar P Sarma V M Sarti M H P Sas E Scapparone J Schambach H S Scheid C Schiaua R Schicker A Schmah C Schmidt H R Schmidt M O Schmidt M Schmidt N V Schmidt A R Schmier J Schukraft Y Schutz K Schwarz K Schweda G Scioli E Scomparin J E Seger Y Sekiguchi D Sekihata I Selyuzhenkov S Senyukov D Serebryakov A Sevcenco A Shabanov A Shabetai R Shahoyan W Shaikh A Shangaraev A Sharma A Sharma H Sharma M Sharma N Sharma S Sharma O Sheibani K Shigaki M Shimomura S Shirinkin Q Shou Y Sibiriak S Siddhanta T Siemiarczuk D Silvermyr G Simatovic G Simonetti B Singh R Singh R Singh R Singh V K Singh V Singhal T Sinha B Sitar M Sitta T B Skaali M Slupecki N Smirnov R J M Snellings C Soncco J Song A Songmoolnak F Soramel S Sorensen I Sputowska J Stachel I Stan P J Steffanic E Stenlund S F Stiefelmaier D Stocco M M Storetvedt L D Stritto A A P Suaide T Sugitate C Suire M Suleymanov M Suljic R Sultanov M Šumbera V Sumberia S Sumowidagdo S Swain A Szabo I Szarka U Tabassam S F Taghavi G Taillepied J Takahashi G J Tambave S Tang M Tarhini M G Tarzila A Tauro G Tejeda Muñoz A Telesca L Terlizzi C Terrevoli D Thakur S Thakur D Thomas F Thoresen R Tieulent A Tikhonov A R Timmins A Toia N Topilskaya M Toppi F Torales-Acosta S R Torres A Trifiró S Tripathy T Tripathy S Trogolo G Trombetta L Tropp V Trubnikov W H Trzaska T P Trzcinski B A Trzeciak A Tumkin R Turrisi T S Tveter K Ullaland E N Umaka A Uras G L Usai M Vala N Valle S Vallero N van der Kolk L V R van Doremalen M van Leeuwen P Vande Vyvre D Varga Z Varga M Varga-Kofarago A Vargas M Vasileiou A Vasiliev O Vázquez Doce V Vechernin E Vercellin S Vergara Limón L Vermunt R Vernet R Vértesi L Vickovic Z Vilakazi O Villalobos Baillie G Vino A Vinogradov T Virgili V Vislavicius A Vodopyanov B Volkel M A Völkl K Voloshin S A Voloshin G Volpe B von Haller I Vorobyev D Voscek J Vrláková B Wagner M Weber S G Weber A Wegrzynek S C Wenzel J P Wessels J Wiechula J Wikne G Wilk J Wilkinson G A Willems E Willsher B Windelband M Winn W E Witt J R Wright Y Wu R Xu S Yalcin Y Yamaguchi K Yamakawa S Yang S Yano Z Yin H Yokoyama I-K Yoo J H Yoon S Yuan A Yuncu V Yurchenko V Zaccolo A Zaman C Zampolli H J C Zanoli N Zardoshti A Zarochentsev P Závada N Zaviyalov H Zbroszczyk M Zhalov S Zhang X Zhang Z Zhang V Zherebchevskii Y Zhi D Zhou Y Zhou Z Zhou J Zhu Y Zhu A Zichichi G Zinovjev N Zurlo

Phys Rev Lett 2020 Oct;125(16):162001

Università di Brescia, Brescia, Italy.

In this Letter, we report the first measurement of the inelastic cross section for antideuteron-nucleus interactions at low particle momenta, covering a range of 0.3≤p<4  GeV/c. The measurement is carried out using p-Pb collisions at a center-of-mass energy per nucleon-nucleon pair of sqrt[s_{NN}]=5.02  TeV, recorded with the ALICE detector at the CERN LHC and utilizing the detector material as an absorber for antideuterons and antiprotons. The extracted raw primary antiparticle-to-particle ratios are compared to the results from detailed ALICE simulations based on the geant4 toolkit for the propagation of (anti)particles through the detector material. The analysis of the raw primary (anti)proton spectra serves as a benchmark for this study, since their hadronic interaction cross sections are well constrained experimentally. The first measurement of the inelastic cross section for antideuteron-nucleus interactions averaged over the ALICE detector material with atomic mass numbers ⟨A⟩=17.4 and 31.8 is obtained. The measured inelastic cross section points to a possible excess with respect to the Glauber model parametrization used in geant4 in the lowest momentum interval of 0.3≤p<0.47  GeV/c up to a factor 2.1. This result is relevant for the understanding of antimatter propagation and the contributions to antinuclei production from cosmic ray interactions within the interstellar medium. In addition, the momentum range covered by this measurement is of particular importance to evaluate signal predictions for indirect dark-matter searches.
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http://dx.doi.org/10.1103/PhysRevLett.125.162001DOI Listing
October 2020

The Prognostic Impact of Epidermal Growth Factor Receptor (EGFR) in Patients with Acute Myeloid Leukaemia.

Indian J Hematol Blood Transfus 2020 Oct 9;36(4):749-753. Epub 2020 Apr 9.

Department of Bioengineering and Technology, Gauhati University, Guwahati, 781014 Assam India.

Expression of Epidermal Growth Factor Receptor (), an important proto-oncogene, regulates cell differentiation, proliferation, cell migration and survival in most of the cancer types. expression has been reported in Acute Myeloid Leukaemia (AML), however, many other reports nullified expression in AML. These contradictory data prompted us to reevaluate the expression of in AML and carry out a comparative survival analysis between expressing and non-expressing AML patients (Children and Acute Promyelocytic Leukaemia patients excluded). Bone marrow and/or peripheral blood samples were collected from 60 adult patients with AML with written informed consent. PCR, Real-Time Taqman gene expression assays were used for the detection of genetic alterations. Statistical analysis was conducted using SPSS software (IBM SPSS 20). In our study, expression was detected in 21 out of 60, in 35% (95% C.I. 23.45-48.48) AML patients. Overall survival was significantly shorter in patients with ( = < 0.01), with an average survival of 18.57 months (95% C.I. 12.42-24.73 months) compared with 31.27 months (95% C.I. 28.19-34.33 months) in patients without . expression was significantly higher in female patients compared to male ( = 0.037).This study confirms the presence of in AML and indicates that expression confers poor prognosis in AML. However, the underlying cause of this adverse prognostic effect has not been identified. Further clinical studies are warranted to determine the exact mechanism through which activity might contribute to AML progression and identify the potential therapeutic target for the reversal of resistance to conventional chemotherapeutics.
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http://dx.doi.org/10.1007/s12288-020-01274-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572979PMC
October 2020

Safety and efficacy of lopinavir/ritonavir combination in COVID-19: A systematic review, meta-analysis, and meta-regression analysis.

Indian J Pharmacol 2020 Jul-Aug;52(4):313-323

Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh, Chandigarh, India.

Background: Being protease inhibitors and owing to their efficacy in SARS-CoV, lopinavir + ritonavir (L/R) combination is being used in the management of COVID-19. In this systematic review and meta-analysis, we have evaluated the comparative safety and efficacy of L/R combination.

Materials And Methods: Comparative, observational studies and controlled clinical trials comparing L/R combination to standard of care (SOC)/control or any other antiviral agent/combinations were included. A total of 10 databases were searched to identify 13 studies that fulfilled the predefined inclusion/exclusion criteria.

Results: No discernible beneficial effect was seen in the L/R group in comparison to SOC/control in terms of "progression to more severe state" (4 studies, odds ratio [OR]: 1.446 [0.722-2.895]), "mortality" (3 studies, OR: 1.208 [0.563-2.592]), and "virological cure on days 7-10" (3 studies, OR: 0.777 [0.371-1.630]), while the L/R combination arm performed better than the SOC/control arm in terms of "duration of hospital stay" (3 studies, mean difference (MD): -1.466 [-2.403 to - 0.529]) and "time to virological cure" (3 studies, MD: -3.272 [-6.090 to - 0.454]). No difference in efficacy was found between L/R versus hydroxychloroquine (HCQ) and L/R versus arbidol. However, in a single randomized controlled trail (open label), chloroquine (CQ) performed better than L/R. The combination L/R with arbidol may be beneficial (in terms of virological clearance and radiological improvement); however, we need more dedicated studies. Single studies report efficacy of L/R + interferon (IFN, either alpha or 1-beta) combination. We need more studies to delineate the proper effect size. Regarding adverse effects, except occurrence of diarrhea (higher in the L/R group), safety was comparable to SOC.

Conclusion: In our study, no difference was seen between the L/R combination and the SOC arm in terms of "progression to more severe state," "mortality," and virological cure on days 7-10;" however, some benefits in terms of "duration of hospital stay" and "time to virological cure" were seen. No significant difference in efficacy was seen when L/R was compared to arbidol and HCQ monotherapy. Except for the occurrence of diarrhea, which was higher in the L/R group, safety profile of L/R is comparable to SOC. Compared to L/R combination, CQ, L/R + arbidol, L/R + IFN-α, and L/R + IFN-1β showed better efficacy, but the external validity of these findings is limited by limited number of studies (1 study each).
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http://dx.doi.org/10.4103/ijp.IJP_627_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722914PMC
October 2020

Tear Meniscus Imaging by Anterior Segment-Optical Coherence Tomography in Medically Controlled Glaucoma.

J Glaucoma 2020 Sep 29. Epub 2020 Sep 29.

Sri Sankaradeva Nethralaya, City-GuwahaD, State Assam, Pin code- 781028, India.

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http://dx.doi.org/10.1097/IJG.0000000000001666DOI Listing
September 2020

Descemet's membrane rupture secondary to forceps-induced birth injury.

Indian J Ophthalmol 2020 Oct;68(10):2253

Sri Sankaradeva Nethralaya, Department of Glaucoma, Guwahati, Assam, India.

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http://dx.doi.org/10.4103/ijo.IJO_149_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727978PMC
October 2020

Structure-Based Repositioning of Approved Drugs for Spike Glycoprotein S2 Domain Fusion Peptide of SARS-CoV-2: Rationale from Molecular Dynamics and Binding Free Energy Calculations.

mSystems 2020 Sep 22;5(5). Epub 2020 Sep 22.

Department of Pharmacology, PGIMER, Chandigarh, India

The membrane-anchored spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a pivotal role in directing the fusion of the virus particle mediated by the host cell receptor angiotensin-converting enzyme 2 (ACE-2). The fusion peptide region of the S protein S2 domain provides SARS-CoV-2 with the biological machinery needed for direct fusion to the host lipid membrane. In our present study, computer-aided drug design strategies were used for the identification of FDA-approved small molecules using the optimal structure of the S2 domain, which exhibits optimal interaction ratios, structural features, and energy variables, which were evaluated based on their performances in molecular docking, molecular dynamics simulations, molecular mechanics/generalized Born model and solvent accessibility binding free energy calculations of molecular dynamics trajectories, and statistical inferences. Among the 2,625 FDA-approved small molecules, chloramphenicol succinate, imipenem, and imidurea turned out to be the molecules that bound the best at the fusion peptide hydrophobic pocket. The principal interactions of the selected molecules suggest that the potential binding site at the fusion peptide region is centralized amid the Lys790, Thr791, Lys795, Asp808, and Gln872 residues. The present study provides the structural identification of the viable binding residues of the SARS-CoV-2 S2 fusion peptide region, which holds prime importance in the virus's host cell fusion and entry mechanism. The classical molecular mechanics simulations were set on values that mimic physiological standards for a good approximation of the dynamic behavior of selected drugs in biological systems. The drug molecules screened and analyzed here have relevant antiviral properties, which are reported here and which might hint toward their utilization in the coronavirus disease 2019 (COVID-19) pandemic owing to their attributes of binding to the fusion protein binding region shown in this study.
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http://dx.doi.org/10.1128/mSystems.00382-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511214PMC
September 2020

Human animal interface of SARS-CoV-2 (COVID-19) transmission: a critical appraisal of scientific evidence.

Vet Res Commun 2020 Nov 14;44(3-4):119-130. Epub 2020 Sep 14.

Department of Pharmacology, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, India.

Coronaviruses are a large family of viruses that are known to infect both humans and animals. However, the evidence of inter-transmission of coronavirus between humans and companion animals is still a debatable issue. There is substantial evidence that the virus outbreak is fueled by zoonotic transmission because this new virus belongs to the same family of viruses as SARS-CoV associated with civet cats, and MERS-CoV associated with dromedary camels. While the whole world is investigating the possibility about the transmission of this virus, the transmission among humans is established, but the interface between humans and animals is not much evident. Not only are the lives of human beings at risk, but there is an equal potential threat to the animal world. With multiple reports claiming about much possibility of transmission of COVID-19 from humans to animals, there has been a significant increase in the number of pets being abandoned by their owners. Additionally, the risk of reverse transmission of COVID-19 virus from companion pets like cats and dogs at home is yet another area of concern. The present article highlights different evidence of human-animal interface and necessitates the precautionary measures required to combat with the consequences of this interface. The Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) have suggested various ways to promote awareness and corroborate practices for helping people as well as animals to stay secure and healthy.
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http://dx.doi.org/10.1007/s11259-020-09781-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487339PMC
November 2020

Efficacy and Safety of Topical Cysteamine in Corneal Cystinosis: A Systematic Review and Meta-Analysis.

Am J Ophthalmol 2020 Sep 2;223:275-285. Epub 2020 Sep 2.

Department of Ophthalmology, Government Medical College and Hospital, Chandigarh, Madras, Chennai, India. Electronic address:

Purpose: To evaluate safety and efficacy of topical cysteamine ophthalmic solution for corneal cystinosis.

Methods: Seven databases were searched (PubMed, OVID, EMBASE, Web of Science, Cochrane Central, Google Scholar, and ClinicalTrials.gov) for relevant studies, using appropriate keywords. Comparative observational studies and randomized controlled trials comparing cysteamine with control or other formulations for treatment of corneal or ophthalmic cystinosis were included. Outcome measurements were improvement or response to therapy, change in corneal cystine crystal score (CCCS), in vivo confocal microscopy score (IVCM), cystine crystal depth, contrast sensitivity (CS), photophobia score, and safety.

Design: Systematic review and meta-analysis.

Results: Seven studies were included. Compared to placebo and control, the cysteamine arm was better in terms of improvements and responses to therapy (2 studies showed a risk ratio [RR] of 16; 95% confidence interval [CI]: 2.30-111.37) and crystal density score (1 study showed a mean difference [MD] of -0.80; 95% CI: -1.56 to -0.04). No significant differences were observed in terms of improvement in CS (1 study showed an RR of 7.00; 95% CI: 0.47-103.27). Compared to cystamine, cysteamine showed benefits in terms of crystal density score (MD -0.94; 95% CI: -1.64 to -0.24). Compared to a newer formulation, the standard formulation (cysteamine [Cystaran]; 0.55% cysteamine hydrochloride + benzalkonium chloride 0.01%) performed better in terms of decreasing CCCS. Another newer, viscous formulation, Cystadrops, performed better than the standard formulation in terms of change in CCCS, IVCM score, corneal crystal depth, and photophobia score; however, local adverse effects and blurring were higher in the group receiving Cystadrops.

Conclusions: Conventional cysteamine (0.1% to 0.3%) performed better than placebo (control) in terms of response to therapy. In terms of decreasing corneal cystine density, cysteamine (0.55%) was better than cystamine (0.55%), and the viscous Cystadrops (0.55%) was better than the standard formulation (0.1%).
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http://dx.doi.org/10.1016/j.ajo.2020.07.052DOI Listing
September 2020

Virtual screening and molecular dynamics study of approved drugs as inhibitors of spike protein S1 domain and ACE2 interaction in SARS-CoV-2.

J Mol Graph Model 2020 12 21;101:107716. Epub 2020 Aug 21.

Dept. of Pharmacology, PGIMER, Chandigarh, India. Electronic address:

Background: The receptor binding domain (RBD) of spike protein S1 domain SARS-CoV-2 plays a key role in the interaction with ACE2, which leads to subsequent S2 domain mediated membrane fusion and incorporation of viral RNA into host cells. In this study we tend to repurpose already approved drugs as inhibitors of the interaction between S1-RBD and the ACE2 receptor.

Methods: 2456 approved drugs were screened against the RBD of S1 protein of SARS-CoV-2 (target PDB ID: 6M17). As the interacting surface between S1-RBD and ACE2 comprises of bigger region, the interacting surface was divided into 3 sites on the basis of interactions (site 1, 2 and 3) and a total of 5 grids were generated (site 1, site 2, site 3, site 1+site 2 and site 2+site 3). A virtual screening was performed using GLIDE implementing HTVS, SP and XP screening. The top hits (on the basis of docking score) were further screened for MM-GBSA. All the top hits were further evaluated in molecular dynamics studies. Performance of the virtual screening protocol was evaluated using enrichment studies.

Result: and discussion: We performed 5 virtual screening against 5 grids generated. A total of 42 compounds were identified after virtual screening. These drugs were further assessed for their interaction dynamics in molecular dynamics simulation. On the basis of molecular dynamics studies, we come up with 10 molecules with favourable interaction profile, which also interacted with physiologically important residues (residues taking part in the interaction between S1-RBD and ACE2. These are antidiabetic (acarbose), vitamins (riboflavin and levomefolic acid), anti-platelet agents (cangrelor), aminoglycoside antibiotics (Kanamycin, amikacin) bronchodilator (fenoterol), immunomodulator (lamivudine), and anti-neoplastic agents (mitoxantrone and vidarabine). However, while considering the relative side chain fluctuations when compared to the S1-RBD: ACE2 complex riboflavin, fenoterol, cangrelor and vidarabine emerged out as molecules with prolonged relative stability.

Conclusion: We identified 4 already approved drugs (riboflavin, fenoterol, cangrelor and vidarabine) as possible agents for repurposing as inhibitors of S1:ACE2 interaction. In-vitro validation of these findings are necessary for identification of a safe and effective inhibitor of S1: ACE2 mediated entry of SARS-CoV-2 into the host cell.
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http://dx.doi.org/10.1016/j.jmgm.2020.107716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442136PMC
December 2020

Stimuli-responsive aggregation-induced fluorescence in a series of biphenyl-based Knoevenagel products: effects of substituent active methylene groups on π-π interactions.

Acta Crystallogr B Struct Sci Cryst Eng Mater 2019 Oct 31;75(Pt 5):775-783. Epub 2019 Aug 31.

Department of Chemistry, Gauhati University, Guwahati, Assam 781014, India.

A series of three biphenyl-based Knoevenagel products (denoted 1a, 1b, 1c) with active methylene groups has been synthesized. Compounds 1a and 1b show strong solid-state fluorescence, whereas 1c displays low emission. Effects of substituent groups in condensed phase packing of the molecules have been investigated and correlated with their photophysical properties. Interestingly, compound 1a exhibits mechanofluorochromism with emission color changes from yellow to green (wavelength shift of 40 nm) after mechanical grinding. Furthermore, fluorescence of 1a and 1b is turned off under alkaline conditions, making them potential candidates for aggregation-enhanced emission-based pH sensors.
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http://dx.doi.org/10.1107/S2052520619009156DOI Listing
October 2019

Assessment of Reference Range of Serum Homocysteine from the Post-therapy Values of Cobalamin and Folate Deficiency Patients.

J Assoc Physicians India 2020 Sep;68(9):36-42

Department of Biotechnology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh.

Objectives: Ideally, the upper reference limit of plasma or serum homocysteine (Hcy) is to be defined from the studies done on individuals with normal cobalamin and folate status. It is difficult to separate the truly healthy (Cobalamin/Folate Replete) individuals from the randomly selected, apparently healthy individuals who are sub-clinically deficient of cobalamin/folate. The present study was aimed at defining the reference values for the serum homocysteine from individuals with normalized cobalamin and folate status.

Methods: In our study, 215 patients with cobalamin, folic acid deficiency were treated accordingly till complete restoration of clinical and laboratory abnormalities. The post-therapy serum Hcy values were used as reference values.

Results: Post-therapy serum Hcy values 12.56 μmol/L (95th percentile), 11.4 μmol/L (85th percentile), 9.8 μmol/L (67th percentile) were seen. The hyperhomocysteinemia was more visible (17.3% gain in prevalence) in the same patient group if interpreted using the post-therapy Hcy value (11.4 μmol/L) as the cut-off. There was no difference between the genders and age groups in the pre or post-therapy Hcy values.

Conclusions: The benefit of the gain in prevalence of disease or the increase in the sensitivity of the test, though small, gets magnified in common diseases and in populous countries. Selection of the individuals is as important as the method or the reagent used in the method when a particular parameter is studied. Repleting the vitamin stores in the confirmed vitamin-deficient patients is more appropriate and easily feasible, since anyway they require treatment, than doing the same on the apparently healthy people. The data thus obtained can be better used as the reference value, for a more meaningful interpretation. The reference range can in turn be used to identify the sub-clinically deficient but asymptomatic people and managed accordingly.
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September 2020

Molecular diagnosis of COVID-19 in different biologic matrix, their diagnostic validity and clinical relevance: A systematic review.

Life Sci 2020 Oct 7;258:118207. Epub 2020 Aug 7.

Department of Pharmacology, PGIMER, Chandigarh, India. Electronic address:

Due to COVID 19 outbreak many studies are being conducted for therapeutic strategies and vaccines but detection methods play an important role in the containment of the disease. Hence, this systematic review aims to evaluate the effectiveness of the molecular detection techniques in COVID-19. For framing the systematic review 6 literature databases (PubMed, EMBASE, OVID, Web of Science, Scopus and Google Scholar) were searched for relevant studies and articles were screened for relevant content till 25th April 2020. Observations from this systematic review reveal the utility of RT-PCR with serological testing as one such method cannot correlate with accurate results. Availability of point of care devices do not conform to sensitivity and specificity in comparison to the conventional methods due to lack of clinical investigations. Pivotal aim of molecular and serological research is the development of detection methods that can support the clinical decision making of patients suspected with SARS-CoV-2. However, none of the methods were 100% sensitive and specific; hence additional studies are required to overcome the challenges addressed here. We hope that the present article with its observations and suggestions will assist the researchers to realize this vision in future.
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http://dx.doi.org/10.1016/j.lfs.2020.118207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411381PMC
October 2020