BACKGROUND: The CHA2DS2-VASc score guides anticoagulation therapy for stroke prevention in non-valvular atrial fibrillation (NVAF) patients. A previous meta-analysis showed a moderate discrimination ability of CHA2DS2-VASc score to detect stroke in patients with & without NVAF. In the presence of newly published data over the past three years, there is a need to recalibrate the existing statistical evidence. METHODS: A comprehensive literature search was conducted across PubMed, Embase, CENTRAL (the Cochrane Library), & Google Scholar from inception till May 2023. All studies evaluating the discrimination ability of the CHA2DS2-VASc score, as measured by the C statistic, for short (<2 years), intermediate (2-5 years), & long-term (>5 years) follow-ups in patients with & without NVAF were included. The generic inverse variance weighted random effects method was used to pool C-statistic & corresponding standard errors (SEs) from each study. RESULTS: A total of 28 studies with a population of 639450 patients were included. Seventeen studies (n=500555) reported the discrimination ability of CHA2DS2-VASc score for NVAF patients, & 11 studies (n=138895) for patients without NVAF. The summary C statistic for short-term follow up was 0.66 (0.62-0.70) for NVAF subgroup. For mid-term follow-up, the pooled C statistic was 0.65 (0.63-0.67), while being 0.63 (0.60-0.66) & 0.68 (0.66-0.70) for the subgroup with NVAF & without NVAF respectively. The CHA2DS2-VASC score showed moderate discrimination [0.66 (0.62-0.70)] at long-term follow up (NVAF [0.58 (0.55-0.61)]; without NVAF [0.67 (0.64-0.70]). CONCLUSION: CHA2DS2-VASc score has moderate & similar discrimination ability for detecting stroke in both NVAF & non-NVAF patients.

Stroke

Statistic

Subgroup analysis

CHA2DS2–VASc score

Study heterogeneity

10.1161/circ.148.suppl_1.17712

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Rabies – epidemiology, pathogenesis, public health concerns and advances in diagnosis and control: a comprehensive review

Veterinary Quarterly (2017)

Rajendra Singh Karam Pal Singh Susan Cherian M. Saminathan Sanjay Kapoor

Rabies is a zoonotic, fatal and progressive neurological infection caused by rabies virus of the genus Lyssavirus and family Rhabdoviridae. It affects all warm-blooded animals and the disease is prevalent throughout the world and endemic in many countries except in Islands like Australia and Antarctica. Over 60,000 peoples die every year due to rabies, while approximately 15 million people receive rabies post-exposure prophylaxis (PEP) annually. Bite of rabid animals and saliva of infected host are mainly responsible for transmission and wildlife like raccoons, skunks, bats and foxes are main reservoirs for rabies. The incubation period is highly variable from 2 weeks to 6 years (avg. 2–3 months). Though severe neurologic signs and fatal outcome, neuropathological lesions are relatively mild. Rabies virus exploits various mechanisms to evade the host immune responses. Being a major zoonosis, precise and rapid diagnosis is important for early treatment and effective prevention and control measures. Traditional rapid Seller's staining and histopathological methods are still in use for diagnosis of rabies. Direct immunofluoroscent test (dFAT) is gold standard test and most commonly recommended for diagnosis of rabies in fresh brain tissues of dogs by both OIE and WHO. Mouse inoculation test (MIT) and polymerase chain reaction (PCR) are superior and used for routine diagnosis. Vaccination with live attenuated or inactivated viruses, DNA and recombinant vaccines can be done in endemic areas. This review describes in detail about epidemiology, transmission, pathogenesis, advances in diagnosis, vaccination and therapeutic approaches along with appropriate prevention and control strategies.

Zoonosis

Lyssavirus

Gold standard (test)

Rabies vaccine

10.1080/01652176.2017.1343516

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Clinical, Laboratory and Imaging Features of COVID-19: A Systematic Review and Meta-analysis

Alfonso J. Rodríguez‐Morales Jaime A. Cardona‐Ospina Estefanía Gutiérrez‐Ocampo Rhuvi Villamizar‐Peña Yeimer Holguin-Rivera

Introduction: An epidemic of Coronavirus Disease 2019 (COVID-19) begun in December 2019 in China, causing primary concern. Among raised questions, clinical, laboratory, and imaging features have been partially characterized in some observational studies. No systematic reviews have been published on this matter. Methods: We performed a systematic review of the literature with meta-analysis, using three databases to assess clinical, laboratory, imaging features, and outcomes of confirmed cases of COVID-19. All the observational studies, and also case reports, were included. The case reports were analyzed separately. We performed a random-effects model meta-analysis to calculate the pooled prevalence and 95%CI. Measures of heterogeneity, including Cochran’s Q statistic, the I2 index, and the τ2 test, were estimated and reported.Results: 660 articles were retrieved. After screening by abstract and title, 27 articles were selected for full-text assessment. Of them, 19 were finally included for qualitative and quantitative analyses. Additionally, 39 case report articles were included and analyzed separately. For >656 patients, fever (88.7%, 95%CI 84.5-92.9%), cough (57.6%, 40.8-74.4%) and dyspnea (45.6%, 10.9-80.4%) were the most prevalent clinical manifestations. Among the patients, 20.3% (95%CI 10.0-30.6%) required ICU, with 32.8% presenting ARDS (95%CI 13.7-51.8), 6.2% (95%CI 3.1-9.3) with shock and 13.9% (95%CI 6.2-21.5%) with a fatal outcome.Discussion: COVID-19 is a new clinical infectious disease, causing considerable compromise, especially in patients with comorbidities, requiring ICU in at least a fifth of them and sometimes with fatal outcomes. Additional research is needed to elucidate factors that may mediate the pathogenesis of the severe and fatal associated disease.

10.20944/preprints202002.0378.v1

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Optimization of Formic Acid-Formalin-Based Decalcification Protocol for Rat Calvarial Bone Histology

Journal of Experimental Biology and Agricultural Sciences (2024)

S. Amitha Banu Khan Sharun Merlin Mamachan Athira Subash Vadapalli Deekshita

Decalcification is crucial in histological processing, particularly for studying mineralized tissues like bone. The choice of decalcification method can significantly impact the quality of histological sections and the preservation of tissue morphology. This study aims to establish a standardized protocol for decalcifying rat calvarial bone using a formic acid-formalin-based decalcification solution. The protocol was systematically optimized and evaluated based on various parameters, including decalcification time, formic acid concentration, and tissue integrity preservation. The decalcification process was evaluated through comprehensive assessments, including gross physical examination, chemical analysis, and radiographic imaging techniques. Our result demonstrated that the 10% formic acid concentration proved most effective for decalcifying rat calvarial bone samples within eight days, excelling in mineral content removal while preserving specimen structural integrity. In contrast, the 5% concentration failed to complete decalcification within ten days, and the 15% compromised sample quality within eight days. Histological analyses confirmed the efficacy of the 10% formic acid concentration in maintaining tissue integrity and achieving optimal staining quality. The standardized protocol presented in this study provides an effective and reliable approach for achieving consistent and high-quality histological sections of rat calvarial bone. An ideal decalcification agent should effectively remove calcium salts, preserve structural integrity and molecular components, facilitate rapid yet minimally damaging decalcification, and ensure ease of handling for laboratory personnel. Further exploration of its applicability to different bone types or species is recommended to broaden its research utility.

Bone decalcification

Histology

10.18006/2024.12(2).218.225

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Editorial: Therapeutic Advances and their Biomedical Perspectives - Part 2

Current Drug Metabolism (2018)

Kuldeep Dhama Yashpal Singh Malik

10.2174/138920021903180508154943

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Deep learning research should be encouraged for diagnosis and treatment of antibiotic resistance of microbial infections in treatment associated emergencies in hospitals

International Journal of Surgery (2022)

Chiranjib Chakraborty Manojit Bhattacharya Ashish Ranjan Sharma Sanjiban Sekhar Roy Md. Aminul Islam

Carvacrol

Satureja

Thymol

10.1016/j.ijsu.2022.106857

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In silico Molecular Docking Analysis Targeting SARS-CoV-2 Spike Protein and Selected Herbal Constituents

Journal of Pure and Applied Microbiology (2020)

Subbaiyan Anbazhagan Ravichandran Karthikeyan Shiv Varan Singh M. Sankar Prasad Thomas

In modern drug discovery, molecular docking analysis is routinely used to understand and predict the interaction between a drug molecule and a target protein from a microbe. Drugs identified in this way may inhibit the entry and replication of pathogens in host cells. The SARS-CoV-2 associated coronavirus disease, COVID-19, has become the most contagious and deadly pandemic disease in the world today. In abeyance of any specific vaccine or therapeutic against SARS-CoV-2, the burgeoning situation urges a need for effective drugs to treat the virus-infected patients. Herbal medicines have been used as natural remedies for treating various infectious diseases since ancient times. The spike (S) protein of SARS-CoV-2 is important for the attachment and pathogenesis of the virus. Therefore, this study focused on the search of useful ligands for S protein among active constituents present in common herbs that could serve as efficient remedies for COVID-19. We analysed the binding efficiency of twelve compounds present in common herbs with the S protein of SARS-CoV-2 through molecular docking analysis and also results are validated with two different docking tools. The binding efficiency of ligands was scored based on their predicted pharmacological interactions coupled with binding energy estimates. In docking analysis, compound “I” (Epigallocatechin gallate (EGCG)) was found to have the highest binding affinity with the viral S protein, followed by compounds, “F” (Curcumin),“D” (Apigenin) and “E” (Chrysophanol). The present study corroborates that compound “I” (EGCG) mostly present in the integrants of green tea, shows the highest potentiality for acting as an inhibitor of SARS-CoV-2. Further, characterization of the amino acid residues comprising the viral binding site and the nature of the hydrogen bonding involved in the ligand-receptor interaction revealed significant findings with herbal compound “I” (EGCG) binding to the S protein at eight amino acid residues. The binding sites are situated near to the amino acids which are required for virus pathogenicity. The findings of the present study need in vivo experiments to prove the utility of “I”, “F”,“D” and “E” compounds and their further use in making herb-based anti-SARS-CoV-2 product in near future. This analysis may help to create a new ethno-drug formulation for preventing or curing the COVID-19.

Docking (animal)

Target protein

Coronavirus

10.22207/jpam.14.spl1.37

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ENTERIC VIRAL ZOONOSES: COUNTERACTING THROUGH ONE HEALTH APPROACH

Journal of Experimental Biology and Agricultural Sciences (2018)

Atul Kumar Verma Sudipta Bhat Shubhankar Sircar Kuldeep Dhama Yashpal Singh Malik

10.18006/2018.6(1).42.52

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Emerging Coronavirus Disease (COVID-19), a Pandemic Public Health Emergency with Animal Linkages: Current Status Update

Yashpal Singh Malik Shubhankar Sircar Sudipta Bhat Obli Rajendran Vinodhkumar Ruchi Tiwari

After the appearance of first cases of ‘pneumonia of unknown origin’ in the Wuhan city, China, during late 2019, the disease progressed fast. Its cause was identified as a novel coronavirus, named provisionally 2019-nCoV. Subsequently, an official name was given as SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) by the International Committee on Taxonomy of Viruses (ICTV) study group. The World Health Organization (WHO) named the Coronavirus disease-2019 as COVID-19. The epidemics of COVID-2019 have been recorded over 113 countries/territories/areas apart from China and filched more than 4292 humans, affecting severely around 1,18,326 cases in a short span. The status of COVID-2019 emergency revised by the WHO within 42 days from Public Health International Emergency (January 30, 2020) to a pandemic (March 11, 2020). Nonetheless, the case fatality rate (CFR) of the current epidemic is on the rise (between 2-4%), relatively is lower than the previous SARS-CoV (2002/2003) and MERS-CoV (2012) outbreaks. Even though investigations are on its way, the researchers across the globe have assumptions of animal-origin of current SARS-CoV-2. A recent case report provides evidence of mild COVID-2019 infection in a pet dog that acquired COVID-2019 infection from his owner in Hong Kong. The news on travellers associated spread across the globe have also put many countries on alert with the cancellation of tourist visa to all affected countries and postponement of events where international visits were required. A few diagnostic approaches, including quantitative and differential real-time polymerase chain reaction assays, have been recommended for the screening of the individuals at risk. In the absence of any selective vaccine against SARS-CoV-2, re-purposed drugs are advocated in many studies. This article discourse the current worldwide situation of COVID-2019 with information on virus, epidemiology, host, the role of animals, effective diagnosis, therapeutics, preventive and control approaches making people aware on the disease outcomes.

Pandemic

Case fatality rate

Coronavirus

Atypical pneumonia

10.20944/preprints202003.0343.v1

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The cholera challenge: How should the world respond?

New Microbes and New Infections (2022)

Jaffar A. Al‐Tawfiq Hitesh Chopra Kuldeep Dhama Ranjit Sah Patricia Schlagenhauf

Cholera

10.1016/j.nmni.2022.101077

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Citations (4)