Antibody mediated cellular phagocytosis in Hepatitis C and SARS-CoV-2 infections

Fc-mediated effector antibody functions including antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent complement deposition (ADCD), and antibody-dependent respiratory burst (ADRB) have been recognised to play a key role in antiviral immunity. Among these effector functions, ADCP alone or together with neutralisation function was shown to correlate with immune protection against several RNA viruses. However, methods that comprehensively study ADCP in HCV and SARS-CoV-2 using whole patient plasma are unavailable thereby precluding understanding to its role in the immunopathogenesis of these diseases. To address these, a robust high throughput flow cytometry-based ADCP assay was developed using THP-1 monocyte cell line as effector cells. This easy-to-use assay was then used to characterise ADCP in patients with HCV and SARS-CoV-2 infections. In patients with chronic HCV infection there was higher envelope 2 (E2) antibody titres while patients that cleared the virus produced antibodies with higher affinities. ADCP function was significantly higher in patients with chronic diseases than clearers and strongly correlated with antibody titre and neutralisation function. Multiple regression analysis showed that anti-E2 IgG is the most important variable for predicting ADCP regardless of disease severity, sex or age. Longitudinal study over 14 months showed anti-E2 antibody titres and ADCP function was maintained in both chronically infected patients and those who cleared the virus while there were variable changes in antibody affinities. In COVID-19, patients with acute disease mounted ADCP early as 10 days after symptom onset, primarily driven by heat labile components in the plasma. In convalescent patients, increased ADCP response significantly correlated with high anti-Spike IgG titres, older age, neutralisation and severe disease. Multiple regression analysis showed that anti-Spike antibody titre was the most important variable for predicting high ADCP. Longitudinal study over 12 months showed an increase in plasma antibody affinity and preservation of ADCP and neutralisation functions despite a decline in the anti-Spike IgG titres by >90%. Collectively, anti-E2 and anti-Spike antibody titres in plasma were the most important predictors of ADCP and neutralisation functions in HCV and SARS-CoV-2 infections respectively. Patients with chronic HCV infection showed higher ADCP when compared to clearers and there was a positive correlation between disease severity and ADCP in SARS-CoV-2 infection. Antibody titres in patients with HCV were maintained longitudinally together with ADCP while changes in affinities of the antibodies were variable. By contrast, in COVID-19 affinities increased overtime while. It is therefore likely preservation of ADCP function in HCV is due maintenance of high antibody titres while in COVID-19 it is due to the improvement in the quality of the antibodies

Isolation and Screening of Antibiotics Producing Streptomyces spp from the Soil Collected around the Root of Alnus nepalensis from Godawari

Actinomycetes are considered as the most invaluable prokaryotes whose genome mining show a great number of putative secondary metabolite biosynthesis pathways as well as gene clusters ranging from 20 to 50 per genome. The genus Streptomyces has been explored for its ability to produce 60% antibiotics worldwide. Alnus nepalensis (Alder) has been found to harbor diverse Eubacteria in its rhizosphere. To evaluate the antibiotic production potential from Actinomycetes, we collected soil samples from rhizosphere (5-7 cm deep) of Alder tree. Primary screening was done by cross-streak method against Multidrug Resistant (MDR) such as Methicillin resistant Staphylococcus auereus (MRSA), Vancomycin resistant Enterococcus feacalis (VRE), Imepenem resistant Acinetobacterbaumannii, Vancomycin resistant Klebsiella pneumonia and Imepenem resistant E. coli as well as Non-MDRs (E. coli, Bacillus subtilis, Klebsiella pneumoniae, S. aeureu and Enterococcus feacalis). Extraction of antibiotics was done using rota-vapour from extract obtained by solid-substrate fermentation technique followed by solvent extraction. Secondary screening was done using well diffusion assay against MDRs. Among total of 40 isolates of Actinomycetes recovered, 14 showed remarkable zone of inhibition (ZOI) to various MDRs. NASA 303 showed 26 mm of ZOI against VRE, NASA 101 had ZOI of 34 mm against MRSA, NASA 319 had 33.7 mm ZOI against Imepenem resistant E. coli, NASA 306 had 36 mm of ZOI against Vancomycin resistant Klebsiella pneumoniae, and NASA 108 showed ZOI of 29.6 mm against Imepenem resistant E. faecalis. This investigation revealed that the Actinomycetes found in Rhizosphere of Alder tree had MDR killing potent antibiotics, which needs to be further explored

EARLY STAGE OF FIBROMYALGIC PAIN IN ADULTS TREATED WITH GABAPENTIN AT KOSHI ZONAL HOSPITAL

Introduction: Early stage of fibromyalgia (FM) is characterized by generalized body ache, fatigue, restlessness sleep, impaired cognitive and anxiety with unknown etiology. The definite diagnosis and treatment for fibromyalgia are not clear, but medications and alternative treatment can help to alleviate or cure early stage of fibromyalgia, among the medications one is gabapentin. Objective: Evaluation of Numerical pain rating scale (NPRS) of fibromyalgia by treating with gabapentin at Koshi Zonal Hospital from May 2016 to March 2018. Methodology : In this cross-sectional study, 50 patients were selected who had already taken more than two times non-steroid anti-inflammatory drugs (NSAIDS) but pain was not relived and those patients were treated with gabapentin(100mg to 300mg) for eight weeks in early stage of fibromyalgia for evaluating pain score in NPRS and complications by using Microsoft Excel Programme. Results: Out of 50 patients, 39 patients had good response, mean age 25.2 (range18-30 years), 37 female patients, mean female age 25.41 years (range 18-30 years), 13 male patients, mean male age 24.62 years (range 18-30 years), mean duration of illness 5.18 weeks ( 4-6 weeks). Conclusion: Patients who were taking gabapentin displayed significant reduction in pain, better sleep, and less fatigue as well as fewer complications

Prevalence and risk of hepatitis e virus infection in the HIV population of Nepal

Background: Infection with the hepatitis E virus (HEV) can cause acute hepatitis in endemic areas in immune-competent hosts, as well as chronic infection in immune-compromised subjects in non-endemic areas. Most studies assessing HEV infection in HIV-infected populations have been performed in developed countries that are usually affected by HEV genotype 3. The objective of this study is to measure the prevalence and risk of acquiring HEV among HIV-infected individuals in Nepal. Methods: We prospectively evaluated 459 Human Immunodeficiency Virus (HIV)-positive individuals from Nepal, an endemic country for HEV, for seroprevalence of HEV and assessed risk factors associated with HEV infection. All individuals were on antiretroviral therapy and healthy blood donors were used as controls. Results: We found a high prevalence of HEV IgG (39.4%) and HEV IgM (15.3%) in HIV-positive subjects when compared to healthy HIV-negative controls: 9.5% and 4.4%, respectively (OR: 6.17, 95% CI 4.42-8.61, p < 0.001 and OR: 3.7, 95% CI 2.35-5.92, p < 0.001, respectively). Individuals residing in the Kathmandu area showed a significantly higher HEV IgG seroprevalance compared to individuals residing outside of Kathmandu (76.8% vs 11.1%, OR: 30.33, 95% CI 18.02-51.04, p = 0.001). Mean CD4 counts, HIV viral load and presence of hepatitis B surface antigen correlated with higher HEV IgM rate, while presence of hepatitis C antibody correlated with higher rate of HEV IgG in serum. Overall, individuals with HEV IgM positivity had higher levels of alanine aminotransferase (ALT) than IgM negative subjects, suggesting active acute infection. However, no specific symptoms for hepatitis were identified. Conclusions: HIV-positive subjects living in Kathmandu are at higher risk of acquiring HEV infection as compared to the general population and to HIV-positive subjects living outside Kathmandu

OUTCOMES OF SHORT-COURSE ORAL CORTICOSTEROID WITH NONSTEROIDAL ANTI-INFLAMMATORY DRUGS FOR EARLY STAGE OFFROZEN SHOULDER AT KOSHI ZONAL HOSPITAL

Introduction: Frozen shoulder or adhesive pericapsulitis is a common condition estimated to be afflicting 2-5 % of the general population. It presents with pain and progressive limitation of both active and passive shoulder movement. Numerous treatment options have been described in the literature. Among them, one of the treatment methods commonly used is oral corticosteroid combined with non-steroidal anti-inflammatory drugs (NSAID). This treatment has been found effective in the early stage of frozen shoulder. Objective: Evaluation of the outcomes in patients with a frozen shoulder after short course oral corticosteroid and NSAIDS. Methodology: In this cross-sectional study, 50 patients having an early stage of frozen shoulder presenting to the outpatient department of Koshi Zonal Hospital from July to December 2017 were included. We included those patients who had already taken more than two courses of NSAID elsewhere but symptoms did not alleviate. We excluded those patients who were diabetic, pregnant and who had a history of trauma in and around the shoulder, neuromuscular disease, suspected pathology such as a tumor, rotator cuff rupture, infection, and arthritis. Oral steroid and NSAID tablets were given to all the patients under coverage of an oral proton pump inhibitor. The shoulder home exercise program was also instituted. The follow-ups were done on the1st,7th,14thand 21stday in the physiotherapy department to measure range of motion (ROM) and shoulder pain and disability index (SPADI) to evaluate the final outcomes. The data was analyzed by using Microsoft Excel program. Results: We found the mean age 49.46 years ( range 30-60 years), duration of illness mean 15 weeks (range 10-19 weeks), considerable improvement of ROM from the baseline. Total SPADI scoresDownloaded from Medico Research Chronicles “Outcomes of short-course oral corticosteroid with non-steroidal anti-inflammatory drugs for early stage of frozen shoulder at Koshi Zonal hospital” RajKharel Y. et al., Med. Res. Chron., 2018, 5 (3), 246-251 DOI No. 10.26838/MEDRECH.2018.5.3.412 Medico Research Chronicles, 2018 247 calculated on the1stdaywas mean total 66.7, the 1st week was mean 49.99, 2ndweekwas mean 38.53 and3rd week was mean 26.63 respectively. Conclusion : The short- course of corticosteroid with NSAID along with shoulder stretch exercises provides rapid pain relief as well as improved ROM and SPADI in a patient with the early-stage frozen shoulder

Outcomes of closed reduction and percutaneous K-Wire fixation versus conventional plaster cast immobilization in the treatment of extra-articular fracture distal end of radius

Introduction: Fracture of the distal end of the radius is among the commonest skeletal injury with diverse treatment options. There is no clear consensus on functional outcomes about diverse treatment options. Objective: To evaluate the accuracy of reduction and compare the functional outcome between closed reduction supplemental percutaneous Kirschner wire fixation and conventional plaster cast immobilization for treatment of fracture distal end of the radius. Methodology: 60 patients with the distal end of radius fracture were selected and divided into two groups, group A (K-wire group): Patients with closed reduction and percutaneous K-wire fixation combined with plaster cast and group B (Cast group): Patients with closed reduction and conventional plaster cast immobilization randomly. Results: All patients in the cast group showed signs of clinical union compared to the k-wire group (96.66%) at 6 weeks. Meanwhile, all patients showed signs of both clinical and radiological union at the subsequent 12 weeks follow up. Patients in both groups showed a progressive decrease in disability scores. Conclusion: Group treated with k wire was more comfortable during the treatment period with less complication as compared to that of the cast group and had better functionality as well as the anatomical outcome. Regardless of the cost, we recommend K- wire fixation overcast application in the treatment of extra-articular distal end radius fracture

Evaluation of antidiabetic efficacy of Murraya koenigii on Streptozotocin induced diabetes in experimental rats

Background: The medicinal plant Murraya koenigii shown to have a wide variety of pharmacological activities (hypoglycemic and hypolipidemic). Objective of this study is the present study was designed to evaluate Antidiabetic and Hypolipidemic property of Murraya koenigii in experimentally induced diabetes in rats.Methods: Experimental diabetes was produced with single dose of Streptozotocin (STZ): 45 mg/kg IP. The rats were randomly allocated in various groups for 37 days. After the confirmation of diabetes on 7th day (>200 mg/dl), hydroalcoholic extract of Murraya koenigii (500 mg/kg) was administered orally to experimental rats from day 7th day and continued for 37 days thereafter. Various antidiabetic (Glucose, HbA1C), metabolic (Lipid profile), safety (pancreatic lipase, Creatinine, SGPT, Histopathology of Liver and Kidney) were evaluated in various group.Results: Efficacy of Murraya koenigii was observed on various parameter of diabetes. Administration of STZ resulted in a significant decrease in diabetic changes (increase in blood glucose, HbA1C), altered lipid profile (p<0.01) in the Control group rats as compared to sham group. Murraya koenigii treatment demonstrated significant antidiabetic indicated by restoration of blood glucose, HbA1C level (p<0.01) compared to Control group. In addition, Murraya koenigii also documented hypolipidemic property of test drug. As per biochemical assessment of Pancreatic lipase, Serum creatinine, SGPT and Histopathological report, the test drug reduce the pancreatic, liver and renal marker and also showed safe to pancreas, Liver and kidney. The histopathological assessment of the liver and kidney confirmed the biochemical findings.Conclusions: The study concluded that the Murraya koenigii possess antidiabetic efficacy

Data_Sheet_1_Participatory Approach to Develop Evidence-Based Clinical Ethics Guidelines for the Care of COVID-19 Patients: A Mixed Method Study From Nepal

Questionnaire and feedback form produced for the study, "Participatory Approach to Develop Evidence-Based Clinical Ethics Guidelines for the Care of COVID-19 Patients: A Mixed Method Study From Nepal"

Participatory Approach to Develop Evidence-Based Clinical Ethics Guidelines for the Care of COVID-19 Patients: A Mixed Method Study From Nepal.

During health emergencies such as the COVID-19 pandemic, healthcare workers face numerous ethical challenges while catering to the needs of patients in healthcare settings. Although the data recapitulating high-income countries ethics frameworks are available, the challenges faced by clinicians in resource-limited settings of low- and middle-income countries are not discussed widely due to a lack of baseline data or evidence. The Nepali healthcare system, which is chronically understaffed and underequipped, was severely affected by the COVID-19 pandemic in its capacity to manage health services and resources for needy patients, leading to ethical dilemmas and challenges during clinical practice. This study aimed to develop a standard guideline that would address syndemic ethical dilemmas during clinical care of COVID-19 patients who are unable to afford standard-of-care. A mixed method study was conducted between February and June of 2021 in 12 government designated COVID-19 treatment hospitals in central Nepal. The draft guideline was discussed among the key stakeholders in the pandemic response in Nepal. The major ethical dilemmas confronted by the study participants (50 healthcare professionals providing patient care at COVID-19 treatment hospitals) could be grouped into five major pillars of ethical clinical practice: rational allocation of medical resources, updated treatment protocols that guide clinical decisions, standard-of-care regardless of patient's economic status, effective communication among stakeholders for prompt patient care, and external factors such as political and bureaucratic interference affecting ethical practice. This living clinical ethics guideline, which has been developed based on the local evidence and case stories of frontline responders, is expected to inform the policymakers as well as the decision-makers positioned at the concerned government units. These ethics guidelines could be endorsed with revisions by the concerned regulatory authorities for the use during consequent waves of COVID-19 and other epidemics that may occur in the future. Other countries affected by the pandemic could conduct similar studies to explore ethical practices in the local clinical and public health context

Prevalence and attributable health burden of chronic respiratory diseases, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

Background Previous attempts to characterise the burden of chronic respiratory diseases have focused only on specific disease conditions, such as chronic obstructive pulmonary disease (COPD) or asthma. In this study, we aimed to characterise the burden of chronic respiratory diseases globally, providing a comprehensive and up-to-date analysis on geographical and time trends from 1990 to 2017. Methods Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, we estimated the prevalence, morbidity, and mortality attributable to chronic respiratory diseases through an analysis of deaths, disability-adjusted life-years (DALYs), and years of life lost (YLL) by GBD super-region, from 1990 to 2017, stratified by age and sex. Specific diseases analysed included asthma, COPD, interstitial lung disease and pulmonary sarcoidosis, pneumoconiosis, and other chronic respiratory diseases. We also assessed the contribution of risk factors (smoking, second-hand smoke, ambient particulate matter and ozone pollution, household air pollution from solid fuels, and occupational risks) to chronic respiratory disease-attributable DALYs. Findings In 2017, 544·9 million people (95% uncertainty interval [UI] 506·9–584·8) worldwide had a chronic respiratory disease, representing an increase of 39·8% compared with 1990. Chronic respiratory disease prevalence showed wide variability across GBD super-regions, with the highest prevalence among both males and females in high-income regions, and the lowest prevalence in sub-Saharan Africa and south Asia. The age-sex-specific prevalence of each chronic respiratory disease in 2017 was also highly variable geographically. Chronic respiratory diseases were the third leading cause of death in 2017 (7·0% [95% UI 6·8–7·2] of all deaths), behind cardiovascular diseases and neoplasms. Deaths due to chronic respiratory diseases numbered 3 914 196 (95% UI 3 790 578–4 044 819) in 2017, an increase of 18·0% since 1990, while total DALYs increased by 13·3%. However, when accounting for ageing and population growth, declines were observed in age-standardised prevalence (14·3% decrease), agestandardised death rates (42·6%), and age-standardised DALY rates (38·2%). In males and females, most chronic respiratory disease-attributable deaths and DALYs were due to COPD. In regional analyses, mortality rates from chronic respiratory diseases were greatest in south Asia and lowest in sub-Saharan Africa, also across both sexes. Notably, although absolute prevalence was lower in south Asia than in most other super-regions, YLLs due to chronic respiratory diseases across the subcontinent were the highest in the world. Death rates due to interstitial lung disease and pulmonary sarcoidosis were greater than those due to pneumoconiosis in all super-regions. Smoking was the leading risk factor for chronic respiratory disease-related disability across all regions for men. Among women, household air pollution from solid fuels was the predominant risk factor for chronic respiratory diseases in south Asia and sub-Saharan Africa, while ambient particulate matter represented the leading risk factor in southeast Asia, east Asia, and Oceania, and in the Middle East and north Africa super-region. Interpretation Our study shows that chronic respiratory diseases remain a leading cause of death and disability worldwide, with growth in absolute numbers but sharp declines in several age-standardised estimators since 1990. Premature mortality from chronic respiratory diseases seems to be highest in regions with less-resourced health systems on a per-capita basis