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Objectives Myositis-specific and associated autoantibodies are important biomarkers in routine clinical use. We assessed local testing performance for myositis autoantibodies by comparing line immunoassay (LIA) to protein radio-immunoprecipitation and identifying clinical characteristics associated with each myositis autoantibody in the MyoCite cohort. Methods Serum samples from patients within the MyoCite cohort, a well-characterized retro-prospective dataset of adult and juvenile idiopathic inflammatory myopathy (IIM) patients in Lucknow, India (2017–2020), underwent LIA at Sanjay Gandhi Postgraduate Institute of Medical Science (SGPGIMS), Lucknow. Immunoprecipitation of 147 IIM patients' serum samples (125 adult-onset, 22 juvenile-onset) was conducted at the University of Bath, with researchers blind to LIA results. LIA performance was assessed against immunoprecipitation as the reference standard, measuring sensitivity, specificity and inter-rater agreement. Univariate and multivariate logistic regression determined clinical associations for specific myositis-specific autoantibodies. Results Immunoprecipitation identified myositis autoantibodies in 56.5% (n  = 83) of patient samples, with anti-Jo1 (n  = 16; 10.9%) as the most common, followed by anti-MDA5 (n  = 14, 9.5%). While LIA showed good agreement for anti-Jo1, anti-PL7 and anti-PL12 (Cohen's κ 0.79, 0.83 and 1, respectively), poor agreement was observed in other subgroups, notably anti-TIF1γ (Cohen's κ 0.21). Strongly positive samples, especially in myositis-specific autoantibodies, correlated more with immunoprecipitation results. Overall, 59 (40.1%) samples exhibited non-congruence on LIA and immunoprecipitation, and κ values for LIAs for anti-TIF1γ, anti-Ku, anti-PmScl, anti-Mi2 and anti-SAE ranged between 0.21 and 0.60. Conclusion While LIA reliably detected anti-Jo1, anti-PL7, anti-PL12, anti-MDA5 and anti-NXP-2, it also displayed false positives and negatives. Its effectiveness in detecting other autoantibodies, such as anti-TIF1γ, was poor. [ABSTRACT FROM AUTHOR]

Objective: Increasing evidence revealed the role of adipokines in carbohydrates and fat metabolism. The present study was designed to evaluate the adiponectin, leptin, and resistin levels in prediabetes subjects and evaluate the relationship between these adipokines and insulin resistance. Methods: A hospital-based descriptive study was conducted for one year. 200 individuals who met the inclusion criteria were enrolled in the study. Based on the oral glucose tolerance test, the study subjects were grouped into healthy controls (n = 100), prediabetic non-obese (n = 61), and prediabetic obese (n = 39). Blood glucose estimation was done by the glucose oxidase peroxidase method. Chemiluminescent immunoassay was used for the measurement of insulin level and homeostasis model assessment-estimated insulin resistance was used for the assessment of insulin resistance. Serum adipokines levels were determined by ELISA. Statistical analysis was performed by using SPSS Software. Results: Serum adiponectin levels decreased significantly in obese prediabetes (7.21 ± 2.15 µg/ml) when compared to non-obese prediabetes (7.28 ± 2.41 µg/ml) and healthy control subjects (13.64 ± 2.88 µg/ml, p < 0.001). Serum leptin levels increased significantly in obese prediabetes (13.59 ± 2.59 ng/ml) when compared to non-obese prediabetes (9.84 ± 2.66 ng/ml) and healthy control subjects (12.28 ± 2.65 ng/ml, p < 0.001). Serum resistin levels increased significantly in obese prediabetes (17.67 ± 3.60 ng/ml) when compared to non-obese prediabetes (17.2 ± 3.93 ng/ml) and healthy control subjects (14.46 ± 4.16 ng/ml, p < 0.001). Adiponectin-leptin ratio decreased significantly in obese prediabetes (0.56 ± 0.22) when compared to non-obese prediabetes (0.79 ± 0.4) and healthy control subjects (1.15 ± 0.37; p < 0.001). Fasting insulin resistance was statistically significant (p < 0.001) in all groups. Conclusion: The present study strongly suggests that the adipokine profile is an ideal diagnostic tool to predict prediabetes and metabolic syndrome, especially among those with insulin resistance. [ABSTRACT FROM AUTHOR]

Current national severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination policy covers children aged >12 years. Unvaccinated, uninfected children remain susceptible to SARS-CoV-2 and play a role in community transmission, as paediatric infection is mostly mild or asymptomatic. To estimate the proportion of susceptible children in a community for public health measures, there is a need to assess the extent of natural infection. We performed a cross-sectional household serosurvey of SARS-CoV-2 antibodies in unvaccinated children aged between 6 and 18 years after the second COVID-19 wave. Anti-SARS-CoV-2 immunoglobin G (IgG) testing in serum was done using chemiluminescence immunoassay. We used a logistic regression model to investigate predicted factors of seropositivity. We observed a high prevalence (weighted average: 68.3%) of anti-SARS-CoV-2 IgG in 2700 enrolled children. Logistic regression for predictors of IgG seropositivity showed lower odds in households with completely vaccinated adults (adjusted odds ratio [OR]: 0.43, 95% confidence interval [CI]: 0.26–0.71, P = 0.0011) compared with households with unvaccinated adults. Other factors for low seropositivity included frontline workers as family members (adjusted OR: 0.69, 95% CI: 0.52–0.91, P = 0.0091) and non-crowded households (adjusted OR: 0.74, 95% CI: 0.61–0.89, P = 0.0019). A high SARS-CoV-2 IgG prevalence in unvaccinated children was indicative of previous exposure to potentially infected contacts. This implies in-person academic activities for children can be continued during future community transmission. Comparatively lower seropositivity in children of completely vaccinated households or frontline workers suggests decreased transmission due to vaccination-induced immunity of family members. Vaccination will still be required in these children to maintain protective IgG levels, particularly in low seroprevalence groups. [Display omitted] [ABSTRACT FROM AUTHOR]

This prospective observational cohort study aimed to establish and compare baseline rates of Clostridioides difficile infection (CDI) in community and hospitalized patients in Nagpur and rural Melghat Maharashtra, including adults aged ≥18 years with a diagnosis of diarrhoea as defined as 3 or more loose stools in a 24 h period. All diarrhoeal samples were tested for CDI using the C. diff Quik Chek Complete enzyme immunoassay. C. difficile-positive stool samples were characterised by toxigenic culture, antimicrobial susceptibility testing and PCR ribotyping. C. difficile testing was performed on 1683 patients with acute diarrhoea. A total of 54 patients (3.21%; 95% CI: 2.42–4.17) tested positive for both the GDH antigen and free toxin. The risk factors for CDI included the presence of co-morbidities, antibiotic usage, and immunosuppression. The detected PCR ribotypes included 053-16, 017, 313, 001, 107, and 216. Our findings show that toxigenic C. difficile is an important but neglected aetiologic agent of infective diarrhoea in Central India. These results underscore the need to enhance the awareness and testing of patients with diarrhoea in India regarding the presence of toxigenic C. difficile, particularly in high-risk individuals with multiple co-morbidities, immunosuppression, and recent or ongoing antibiotic exposure or hospitalization. [ABSTRACT FROM AUTHOR]

INTRODUCTION: HIV fourth-generation assay, designed for the detection of HIV p24 antigen along with anti-HIV antibodies of both immunoglobulin M and immunoglobulin G type against HIV 1 and HIV 2 viral antigens, have helped in the early detection of HIV infection and supports in minimizing the transmission risk in the acute phase of infection. The objective of this study was to evaluate the analytical and clinical performance of HIV fourth-generation assay based on enhanced chemiluminescence technology. MATERIALS AND METHODS: The analytical performance of the assay was evaluated in terms of accuracy, precision, limit of detection, type of sample (serum vs. plasma), cross-reactivity (with other transfusion transmissible infections markers), and interference (with endogenous substances). Proficiency control material included kit-controls, archived known positive donor samples, third-party controls, and World Health Organization (WHO)/National Institute for Biological Standards and Controls (NIBSC, MHRA, UK) controls. The clinical performance was evaluated using routine donor and patient samples received during the study period. RESULTS: HIV fourth-generation assay showed reliable and reproducible results measured in terms of coefficient of variation % with kit-controls, archived known positive donor samples, third-party controls, and WHO international standards for anti-HIV 1 and 2 antibodies, HIV1 p24 antigens and HIV2 p26 antigen controls. The analytical sensitivity of the HIV fourth-generation assay was found to be 0.1 IU/mL of HIV1 p24 antigen control and there was no cross-reactivity or interference observed. In the clinical performance of the assay, HIV fourth-generation assay showed reliable performance in both donor and patient samples. CONCLUSION: HIV fourth-generation assay meets the requirements for its use as a screening assay for HIV infection based on the analytical and clinical performance of the assay. [ABSTRACT FROM AUTHOR]

Background /purpose: Leptin—a protein hormone that plays vital role in the regulation of glucose homeostasis and insulin sensitivity, involved in regulating the circadian rhythms of gonadotropic, thyrotropic and adrenal axes in the endocrine system. This cross-sectional study was undertaken to correlate serum leptin levels and other demographic and biochemical parameters between prediabetic cases and control subjects of Kashmiri population. Furthermore, association of serum leptin levels with various demographic and biochemical parameters along with insulin resistance in pre-diabetic subjects was elucidated. In our study, pre-diabetic cases (n = 212) and healthy controls (n = 196) were enrolled. Methods: All study subjects underwent anthropometric assessment. Serum samples of all study subjects were analysed for biochemical parameters employing the principle of spectrophotometry and leptin levels using sandwich enzyme-linked immunosorbent assay (ELISA). Insulin levels of prediabetic cases were deduced by chemiluminescent micro particle immunoassay (CMIA) technology and thereby calculating their insulin resistance. Results: The cases had statistically increased leptin levels, lipid profile and obesity as compared to controls (p ≤ 0.05). Our study, showed a positive correlation between elevated leptin levels and increased lipid levels (total cholesterol, triglycerides; TG and very low density lipoproteins-cholesterol; VLDL-C) in prediabetics (p < 0.001). Conclusion: Beyond adiposity, leptin levels may increase the risk of pre-diabetes in Kashmiri population. Since the secretion, estimation and measurements of leptins are modest in contrast to insulin levels; therefore, leptin levels can also be included in the routine measurement as an indicator of metabolic syndrome and/or T2DM. [ABSTRACT FROM AUTHOR]

Background: Telomeres and telomerase are considered cardinal biomarkers of cellular aging. Shorter telomeres and low telomerase activity have been associated with obesity and accelerated aging. Objective: To compare the effects of a yoga-based lifestyle intervention (YBLI) with the standard of care (SOC) on cellular aging by estimating telomere length (TL) and telomerase activity in obesity. Design and setting: A parallel, two-arm, randomized-controlled trial was conducted at the Integral Health Clinic, Department of Physiology, All India Institute of Medical Sciences, New Delhi, from March 2017 to October 2019. Participants: Obese (n = 72), body mass index (BMI), 25-35 kg/m², aged 20-45 years, male (21), and female (51). Intervention: Seventy-two obese participants were randomized to receive either a 12-week SOC (n = 36) or YBLI (n = 36). SOC included management of obesity as per Indian guidelines including a hypocaloric individualized diet and physical activity. The pretested YBLI included asana (physical postures), pranayama (breathing exercises), and meditation. Methods: Blood samples were collected from both the groups at baseline, 2, 4, and 12 weeks. DNA was extracted from peripheral blood mononuclear cells. TL was measured by quantitative PCR, and serum telo-merase levels by immunoassay. Outcome measures: Primary outcome measures were the changes in the TL and telomerase levels between the two groups at week 12. Secondary outcome measures were the changes in TL and telomerase, and an-thropometric parameters (body weight, BMI, waist-to-hip ratio) at 2, 4, and 12 weeks of intervention in both SOC and YBLI groups. Results: There were no significant changes in TL and telomerase levels between the groups at week 12. The TL was significantly greater in the YBLI group versus the SOC group (p < 0.0001) at 2 weeks. The anthropometric and physiological parameters were influenced positively by both SOC and YBLI. Conclusion: The study did not meet the primary objective, although the results are suggestive of a positive impact of YBLI on aging in obesity as noted within the YBLI group. However, the results should be interpreted carefully, and in the light of other published data. Larger studies to better understand the possible positive benefits of YBLI on cellular aging are recommended. [ABSTRACT FROM AUTHOR]

BACKGROUND: Few international studies have reported the prevalence of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in healthy, asymptomatic blood donors. These findings have definitely raised queries regarding blood safety and transfusion-transmitted coronavirus disease (COVID)-19. We conducted this first anti-SARS-CoV-2 seroprevalence survey among the healthy blood donors in Eastern India. MATERIALS AND METHODS: The study included 611 healthy blood donors who donated whole blood (WB) in our blood center. For detailed analysis, social and demographic details of all donors like gender, age, weight, occupation, and place of residence were included. Donor eligibility criteria for WB donation were followed as per existing national guidelines. Residual serum samples leftover after screening the mandatory infectious markers were tested for the presence of anti-SARS-CoV-2 IgG directed against domain S1 and S2 of the SARS-CoV-2 spike protein using automated enhanced chemiluminescence technology following the manufacturer's instructions. RESULTS: The mean overall seroprevalence of anti-SARS-CoV-2 antibody in blood donors was observed to be 4.4% (95% confidence interval 3.8–4.9) with a monthly increasing trend. Seroprevalence adjusted for sensitivity and specificity of the assay was 4.1%. The mean S/Co values of reactive donor samples were observed to be 2.99 and 3.42 in June and July 2020, respectively (P = 0.013). No significant variation in seroprevalence rate was observed among donor variables like donor age, gender, profession, and educational qualification. A higher significant prevalence of antibody was observed among voluntary donors and donors residing in suburban areas (P < 0.05). Among the ABO blood groups, no statistical significance of seroprevalences was observed among the various ABO blood groups. CONCLUSION: We conclude that despite many limitations in the current study, we found 4.4% seroprevalence of anti-SARS-CoV-2 antibody in the asymptomatic, healthy, epidemiologically, and medically screened blood donors. These data are definitely the tip of an iceberg and signify much higher seroprevalence in the normal population and indicate that protective measures like masking and social distancing should remain implemented for a long term. [ABSTRACT FROM AUTHOR]

Anti-neutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis (AAV) is a small vessel vasculitis with insufficient epidemiological estimates in India. We aimed to determine demographic, clinical features, and laboratory diagnosis of AAV patients presenting to a large tertiary care centre in India. 1289 patient samples were screened for ANCA by indirect immunofluorescence test (IIFT) and confirmation of ANCA target antigens was done by line immunoassay. Association between IIFT and LIA was determined in AAV. By IIFT, ANCA was detected in 13.0% (168 out of 1289), of which 23.8% (40/168) were positive with P-ANCA pattern, 25.0% (42/168) were positive with C-ANCA and 47.6% (80/168) showed an atypical pattern. On evaluation with a line immunoassay, 6.7% (86/1289) were positive out of which 52.3% (45/86), 41.9% (36/86), 8.8% (6/86) were positive for anti-MPO, anti-PR3, and anti-GBM respectively. In eosinophilic granulomatosis with polyangiitis (EGPA) 87.5% (7/8), and microscopic polyangiitis (MPA/RLV) 91.3% (21/23), anti-MPO was the predominantly observed antibody. In granulomatosis with polyangiitis (GPA) anti-PR3 antibody was predominant in 87.5% (28/32) cases. Out of 168 IIF positive samples 8, 32, and 23 cases of EGPA, GPA, and MPA/RLV were observed respectively. The primary aim of the study was to provide single-centre data to determine the laboratory diagnosis of AAV. A combination of IIFT and LIA was found to be an optimum testing strategy for the laboratory diagnosis of AAV. [ABSTRACT FROM AUTHOR]

Objective: Adolescents with perinatally acquired HIV (AWH) are at an increased risk of poor cognitive development yet the underlying mechanisms remain unclear. Circulating galectin-9 (Gal-9) has been associated with increased inflammation and multimorbidity in adults with HIV despite antiretroviral therapy (ART); however, the relationship between Gal-9 in AWH and cognition remain unexplored., Design: A cross-sectional study of two independent age-matched cohorts from India [AWH on ART ( n  = 15), ART-naive ( n  = 15), and adolescents without HIV (AWOH; n  = 10)] and Myanmar [AWH on ART ( n  = 54) and AWOH ( n  = 22)] were studied. Adolescents from Myanmar underwent standardized cognitive tests., Methods: Plasma Gal-9 and soluble mediators were measured by immunoassays and cellular immune markers by flow cytometry. We used Mann-Whitney U tests to determine group-wise differences, Spearman's correlation for associations and machine learning to identify a classifier of cognitive status (impaired vs. unimpaired) built from clinical (age, sex, HIV status) and immunological markers., Results: Gal-9 levels were elevated in ART-treated AWH compared with AWOH in both cohorts (all P  < 0.05). Higher Gal-9 in AWH correlated with increased levels of inflammatory mediators (sCD14, TNFα, MCP-1, IP-10, IL-10) and activated CD8 + T cells (all P  < 0.05). Irrespective of HIV status, higher Gal-9 levels correlated with lower cognitive test scores in multiple domains [verbal learning, visuospatial learning, memory, motor skills (all P  < 0.05)]. ML classification identified Gal-9, CTLA-4, HVEM, and TIM-3 as significant predictors of cognitive deficits in adolescents [mean area under the curve (AUC) = 0.837]., Conclusion: Our results highlight a potential role of Gal-9 as a biomarker of inflammation and cognitive health among adolescents with perinatally acquired HIV., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Objectives: There are limited published data on association of results from commercial serological anti‐SARS‐CoV‐2 IgG antibody CLIA (chemiluminescent immunoassay) assays with neutralizing antibodies. This study was undertaken with an objective to correlate sample‐to‐cut‐off (S/Co) ratio of CLIA antibody tests with inhibition activity, which may then serve as a valuable guide for labelling plasma as COVID convalescent plasma (CCP) for therapy and assessing vaccine efficacy. Materials and Methods: A total of 139 donor serum samples who were previously RT‐PCR positive and had recovered completely from COVID‐19 at least 28 days prior to collection of samples were recruited at three sites. The samples were analysed for S/Co ratio and per cent inhibition activity with VITROS SARS‐CoV‐2 IgG chemiluminescent assay and GenScript cPass SARS‐CoV‐2 Surrogate Virus Neutralization Test (sVNT) kit, respectively. Linear regression equation and receiver operating characteristic (ROC) curve were used to check the proposed model of comparing S/Co with per cent inhibition. Results: The results indicate very good correlation between the S/Co ratio of the chemiluminescent IgG assay and the neutralization activity depicted by per cent inhibition on sVNT assay. S/Co ratio of 4·04 (low‐titre) and 8·19 (high‐titre) correlated with 30% and 68% inhibition, respectively. Conclusion: Chemiluminescent SARS‐CoV‐2 IgG assay can be used as a semi‐quantitative test, with a cut‐off of >8·19S/Co ratio for selecting donors for convalescent plasma therapy and assessing efficacy of vaccination. [ABSTRACT FROM AUTHOR]

Objectives: To estimate the regional cutoff of optical density (OD) values for immunoglobulin M (IgM) antibodies against Orientia tsutsugamushi in serum and cerebrospinal fluid (CSF) for clinical diagnosis of scrub typhus and immunoglobulin G (IgG) antibodies in serum for sero-epidemiology in Gorakhpur, Uttar Pradesh, India. Methods: We used data from a serological investigation of acute encephalitis syndrome patients (n=407) during the 2016 outbreak in Gorakhpur, India to determine the cutoff for OD values for IgM antibodies, and from community-based serosurveys (n=1991) to estimate the cutoff for OD values for IgG antibodies. Results: We determined regionally relevant cutoff for OD values of 0.76 for IgM antibodies in serum and 0.22 in cerebrospinal fluid for scrub typhus diagnosis. For serosurveys, IgG antibody cutoff was 1.5. Conclusions: We have proposed locally relevant cutoffs for scrub typhus endemic regions, which may be useful for correctly classifying infected population. [ABSTRACT FROM AUTHOR]

Objectives: To estimate the regional cutoff of optical density (OD) values for immunoglobulin M (IgM) antibodies against Orientia tsutsugamushi in serum and cerebrospinal fluid (CSF) for clinical diagnosis of scrub typhus and immunoglobulin G (IgG) antibodies in serum for sero-epidemiology in Gorakhpur, Uttar Pradesh, India. Methods: We used data from a serological investigation of acute encephalitis syndrome patients (n=407) during the 2016 outbreak in Gorakhpur, India to determine the cutoff for OD values for IgM antibodies, and from community-based serosurveys (n=1991) to estimate the cutoff for OD values for IgG antibodies. Results: We determined regionally relevant cutoff for OD values of 0.76 for IgM antibodies in serum and 0.22 in cerebrospinal fluid for scrub typhus diagnosis. For serosurveys, IgG antibody cutoff was 1.5. Conclusions: We have proposed locally relevant cutoffs for scrub typhus endemic regions, which may be useful for correctly classifying infected population. [ABSTRACT FROM AUTHOR]

Objectives: To assess the vitamin D status among the study population and to determine the association between Vitamin D deficiency and dyslipidemia. Materials and Methods: This cross sectional study included medical undergraduates aged between 18-20 years with no major illness or medication history. Complete fasting lipid profile was measured by photometry method and biochemical estimation of serum 25-hydroxy 25(OH)D was done using automated chemiluminescent immunoassay. Vitamin D status and lipid profile parameters were compared using Pearson Chi-square test. P < 0.05 was considered as statistically significant. Descriptive statistics such as mean, standard deviation, and inferential statistics like Chi-square test were used. Results: 96.6% were vitamin D deficient and 40% of the subjects were dyslipidemic. There was no significant association between Vitamin D status and Lipid profile. Conclusion: High prevalence of Vitamin D deficiency but no significant association between vitamin D deficiency and dyslipidemia. [ABSTRACT FROM AUTHOR]

Background: Gain‐of‐function of ATP‐sensitive K+ (KATP) channels because of mutations in the genes encoding SUR1 (ABCC8) or Kir6.2 (KCNJ11) is a major cause of neonatal diabetes mellitus (NDM). Our aim is to determine molecular defects in KATP channels caused by ABCC8 mutations in Asian Indian children with NDM by in vitro functional studies. Methods: Wild‐type (WT; NM_000352.4) or mutant sulfonylurea receptor 1 (SUR1) and Kir6.2 were co‐expressed in COSm6 cells. Biogenesis efficiency and surface expression of mutant channels were assessed by immunoblotting and immunostaining. The response of mutant channels to cytoplasmic ATP and ADP was assessed by inside‐out patch‐clamp recordings. The response of mutant channels to known KATP inhibitors in intact cells were determined by 86Rb efflux assays. Results: Five SUR1 missense mutations, D212Y, P254S, R653Q, R992C, and Q1224H, were studied and showed increased activity in MgATP/MgADP. Two of the mutants, D212Y and P254S, also showed reduced response to ATP4− inhibition, as well as markedly reduced surface expression. Moreover, all five mutants were inhibited by the KATP channel inhibitors glibenclamide and carbamazepine. Conclusions: The study shows the mechanisms by which five SUR1 mutations identified in Asian Indian NDM patients affect KATP channel function to cause the disease. The reduced ATP4− sensitivity caused by the D212Y and P254S mutations in the L0 of SUR1 provides novel insight into the role of L0 in channel inhibition by ATP. The results also explain why sulfonylurea therapy is effective in two patients and inform how it should be effective for the other three patients. [ABSTRACT FROM AUTHOR]

Data on specific causes of mortality in South East Asians with type 2 diabetes mellitus (T2DM) remain scarce. We followed 2061 outpatients with T2DM (Chinese 63%, Malays 20%, and Asian Indians 17%) for an average of 5.5 (standard deviation = 2.9) years and identified 365 death events by data linkage with national death registry. Cardiovascular disease was the main cause of mortality (44%), followed by renal disease (17%), infection (17%), cancer (14%), and others causes (8%). Survival analyses revealed that risks for all-cause and cause-specific mortality vary greatly among ethnic groups. Presence of diabetic kidney disease was an independent risk factor for death attributable to cardiovascular disease, renal disease, and infection, while HbA1c level predicted all major causes of deaths even after accounting for multiple other risk factors. These data reinforce the importance of glycemic control and prevention of diabetic kidney disease for mitigation of mortality burden in multiethnic Asians with T2DM. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Hemostatic disorders are often missed in women with bleeding particularly menorrhagia. Preexisting hemostatic disorders are now known as common risk factor for postpartum hemorrhage and prolonged bleeding in puerperium. Females with bleeding complaints constitute an important population referred to hematology clinic. Hence, we aim to evaluate the type and frequency of hemostatic disorders among females presenting with bleeding in a tertiary care hospital and a basic hemostatic laboratory. Methods: Three‐year data were retrospectively analyzed for 200 females with various bleeding complaints. Due to resource constraints, a hemostatic workup was done with prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen assay, clot solubility test, mixing studies, specific factor assays, platelet function test, and von Willebrand factor antigen level. Results: A total of 200 females were investigated to identify the cause of their bleeding. Thirty‐five of 200 (17.5%) females were found with an underlying bleeding disorder. Of these 35 females, 65.7% presented with bleeding from more than 1 site. Most common bleeding manifestation was spontaneous bruising in 18 of 35 (51.4%) patients followed by petechiae (48.6%). Inherited bleeding disorders were noted in majority. The most common inherited bleeding disorder identified was von Willebrand disease (VWD) in 34.3% females. Second most common disorder was Glanzmann's thrombasthenia accounting for 22.8%. Rare coagulation factor deficiency, such as factors VII, X, and XIII deficiencies, was noted. Three cases revealed acquired causes of coagulation defects. Conclusion: Underlying hemostatic defects should be searched for in women with unexplained bleeding complaints. This will not only help in diagnosis but also in proper management for future hemostatic challenges. [ABSTRACT FROM AUTHOR]

Background. Chronic obstructive pulmonary disease (COPD) is a devastating condition with limited pharmacotherapeutic options and exceptionally high public-health burden globally as well as in India. Tobacco smoking is the primary cause for COPD among men in India. Systemic inflammation involving altered regulation of cytokines controlling the host defense mechanism is a hallmark of COPD pathogenesis. However, biomarker discovery studies are limited among Indian COPD patients. Methods. We assessed the serum concentrations [median (25th-75th percentile) pg/ml] of interleukin (IL)-2,4,6,8,10, granulocyte macrophage colony stimulating factor (GM-CSF), interferon gamma (IFN-γ), and tumor necrosis factor alpha (TNF-α) using a multiplexed immunoassay. Our study cohort consisted of 30 tobacco smokers with COPD (TS COPD) and 20 tobacco smokers without COPD (TS CONTROL) from South India. The study population was matched for age, sex (male), and tobacco consumption (pack-years). COPD was diagnosed according to the global initiative for chronic obstructive lung disease (GOLD) criteria of persistent airflow obstruction determined by the ratio of postbronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) of <0.7. A validated structured questionnaire-based survey [Burden of Obstructive Lung Disease (BOLD) study] and spirometry were performed during house to house visit of the field study. Statistical analysis included nonparametric (two-tailed) Mann–Whitney U and Spearman rank test, as appropriate (significance: p<0.05). Results. Serum GM-CSF [69.64 (46.67, 97.48); 36.78 (30.07, 53.88), p=0.014], IFN-γ [51.06 (17.00, 84.86); 11.70 (3.18, 32.81), p=0.017], IL-4 [9.09 (1.8, 19.9); 1.8 (1.8, 4.46); p=0.024], and TNF-α [20.68 (5.5, 29.26); 3.5 (3.5, 4.5); p<0.001] concentrations (pg/ml) were increased in TS COPD subjects compared to TS CONTROL. A weak correlation between lung function parameters and cytokine concentrations was detected. Conclusion. Our pilot study reveals GM-CSF, IFN-γ, IL-4, and TNF-α as plausible COPD susceptibility biomarkers within the investigated South Indian population that needs to be validated in a larger cohort. [ABSTRACT FROM AUTHOR]

BACKGROUND: Alloantibodies may be detected in blood donors who have either been transfused previously or female donors with previous obstetric events. These antibodies can occasionally cause severe transfusion reaction, if a large amount of plasma or whole blood is transfused, as in massive transfusions and pediatric patients. AIMS: The present study aims to assess the prevalence of red cell antibodies in healthy blood donors at a tertiary care hospital-based blood bank in India. MATERIALS AND METHODS: A total of 82,153 donor samples were screened for irregular red cell antibodies between January 2012 and December 2015 at the Department of Transfusion Medicine, Indraprastha Apollo Hospitals, New Delhi. Antibody screening was performed by solid phase method using Immucor Capture-R ready screen (pooled cells) on fully automated immunohematology analyzer Galileo Neo (Immucor Inc., Norcross, GA, USA). Positive tests were further confirmed using Capture-R ready screen (4 cell panel). Advanced investigations to identify the antibody/ies were performed on confirmed positive samples. Antibody identification was conducted using various cell panels (Immucor Capture-R Ready-ID, Panocell-10, Ficin Treated). An advanced technique such as adsorption and elution was performed as per requirement. RESULTS: Screening with pooled cells and 4 cell panel was positive in 227 donors (0.27%), 150 of these donors had autoantibodies, 1 had autoantibodies with underlying alloantibody anti-Jka (0.001%), and 76 had alloantibodies (0.09%) alone in their plasma. Anti-M was the most common antibody (43 donors) identified, followed by anti-D (21 donors). Anti-N was detected in 4; anti-Jka, anti-C, and anti-E in two donors each followed by anti-P1 and anti-Leb in 1 donor. CONCLUSION: Antibodies against red cells can be present in healthy donors detection of which is important in providing safe blood to the patient. The prevalence of red blood cell antibody in healthy donors in this study was found to be 0.27%, while the prevalence of alloantibodies was 0.09%. The majority of alloantibodies were anti-M (56.57%) and anti-D (27.63%). [ABSTRACT FROM AUTHOR]

Background: The mechanism of development of atrial fibrillation (AF) in patients undergoing coronary artery bypass grafting (CABG) has not been clearly defined, and the involvement of multiple factors such as advanced age, withdrawal of β-blockers, inadequate atrial protection, and electrolyte imbalance, particularly hypomagnesemia has been documented by several authors. Despite all the available pharmacologic prophylaxis, incidence of AF still remains high in this group of patients. This unexplained cause could be genetic inheritance of endothelin-1 (ET-1) gene which is thought to have a pro-arrhythmogenic effect.Aim: This study aims to investigate the relationship between plasma ET-1 concentrations, ET-1 gene polymorphisms in loci -1370 T/G, -134 (3A/4A) Ins/del, Lys198Asn (G/T), and occurrence of AF in patients undergoing CABG.Methodology: Ninety-eight nonrelated, nondiabetic patients over a period of 4 years undergoing routine CABG were selected for the present study. All patients were genotyped for three single nucleotide polymorphisms (SNPs) in loci -1370 T/G, -134 (3A/4A) Ins/del, and Lys198Asn (G/T) in the ET-1 gene by gene sequencing. The plasma ET-1 concentrations were measured using an ET immunoassay.Results: Plasma ET-1 concentrations were higher in AF+ group (P = 0.001) as compared to AF- group. The allele frequencies between AF+ and AF- group were significantly different only with respect to the Lys198Asn (G/T) SNP of the ET-1 gene.Conclusion: The study described the possible correlation of polymorphism of ET gene in CABG population from India. The ET-1 gene might play a disease-modifying role in atrial fibrillation. [ABSTRACT FROM AUTHOR]

Background: Data are scant on bone health in endocrinopathies from India. This study evaluated bone mineral density (BMD) loss in endocrinopathies [Graves’ disease (GD), type 1 diabetes mellitus (T1DM), hypogonadotrophic hypogonadism (HypoH), hypergonadotropic hypogonadism (HyperH), hypopituitarism, primary hyperparathyroidism (PHPT)] as compared to age-related BMD loss [postmenopausal osteoporosis (PMO), andropause]. Materials and Methods: Retrospective audit of records of patients >30 years age attending a bone clinic from August 2014 to January 2016 was done. Results: Five-hundred and seven records were screened, out of which 420 (females:male = 294:126) were analyzed. A significantly higher occurrence of vitamin D deficiency and insufficiency was noted in T1DM (89.09%), HyperH (85%), and HypoH (79.59%) compared to age-related BMD loss (60.02%; P < 0.001). The occurrence of osteoporosis among females and males was 55.41% and 53.97%, respectively, and of osteopenia among females and males was 28.91% and 32.54%, respectively. In females, osteoporosis was significantly higher in T1DM (92%), HyperH (85%), and HypoH (59.26%) compared to PMO (49.34%; P < 0.001). Z score at LS, TF, NOF, and greater trochanter (GT) was consistently lowest in T1DM women. Among men, osteoporosis was significantly higher in T1DM (76.67%) and HypoH (54.55%) compared to andropause (45.45%; P = 0.001). Z score at LS, TF, NOF, GT, and TR was consistently lowest in T1DM men. In GD, the burden of osteoporosis was similar to PMO and andropause. BMD difference among the study groups was not significantly different after adjusting for body mass index (BMI) and vitamin D. Conclusion: Low bone mass is extremely common in endocrinopathies, warranting routine screening and intervention. Concomitant vitamin D deficiency compounds the problem. Calcium and vitamin D supplementations may improve bone health in this setting. [ABSTRACT FROM AUTHOR]

Objective: To describe the incidence, severity and etiology of diarrheal disease in infants and young children residing in an urban slum community in Southern India. Setting: Three contiguous urban slums in Vellore, Tamil Nadu. Participants: 452 children participating in a birth cohort study on diarrheal disease; 373 completed three years of follow-up. Outcome measures: Diarrheal incidence (obtained by twiceweekly home visits) and severity (assessed by the Vesikari scoring system), and etiological agents associated with diarrhea (through examination of stool specimens by bacteriologic culture, rotavirus enzyme immunoassay, PCR for norovirus and microscopy for parasites). Results: A total of 1856 diarrheal episodes were reported in 373 children. The overall incidence rate of diarrhea was 1.66 episodes per child year for three years, with 2.76 episodes per child year in infancy. The incidence peaked during the months of July and August. Severe diarrhea formed 8% of the total episodes. Rotavirus was the most common pathogen detected, being identified in 18% of episodes. Good hygiene status resulted in 33% protection against moderate-to-severe diarrhea. Conclusions: This study highlights the burden of diarrheal disease and the important etiological agents of childhood diarrhea in Southern India. Promotion of hygienic behavior through health education may help reduce diarrheal incidence in this and similar communities. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrinological disorders among women of reproductive age and the leading cause of female infertility. This study intends to evaluate the lipid profile, hormonal levels [free T3 (fT3), free T4 (fT4), thyroid stimulating hormone (TSH), insulin, luteinizing hormone (LH), follicle stimulating hormone (FSH), and prolactin] in PCOS women from Nellore and its surrounding districts of Andhra Pradesh, India. Materials and Methods: This cross-sectional study included 80 newly diagnosed PCOS women and an equal number of age and body mass index (BMI) matched healthy controls. We used the photometry methods to determine serum glucose levels and the lipid profile. An immunoturbidometry method was employed to measure high sensitive C-reactive protein (hsCRP). All hormonal parameters were measured using chemiluminescence immunoassays. Insulin resistance was evaluated using the homeostatic model assessment-insulin resistance (HOMA-IR) method. Statistical analysis was done using SPSS software version 20.0. Results: The PCOS patients presented statistically higher levels of total cholesterol (TC), triglycerides (TG) and low density lipoprotein cholesterol (LDL-c, P<0.0001) when compared to those of controls. PCOS patients had elevated fasting glucose, hsCRP, fasting insulin, TSH, LH and prolactin levels (P<0.001). An increased LH/FSH ratio (>1.5) was seen in women with PCOS compared with control women. In addition, we observed a direct correlation between fasting insulin with fasting glucose and HOMA-IR. LH was inversely proportional to BMI. Conclusion: The present study showed a higher prevalence of insulin resistance, dyslipidemia, and hypothyroidism in PCOS women. Furthermore this study showed increased LH concentrations, a higher LH/FSH ratio, and higher prolactin levels in PCOS women. [ABSTRACT FROM AUTHOR]

Recent scientific evidence suggests there is high prevalence of Vitamin D deficiency in India. There is paucity of scientific data on Vitamin D status in population residing at high altitude regions in India. Hence, the present study was undertaken to determine Vitamin D status of adult population residing at altitude of 4000 meter and above in Himachal Pradesh, India. A total of 105 subjects aged 19-56 years were recruited (3 subjects per village) from 35 villages in Lahaul & Spiti district. The data on socio-demographic profile was collected by administering a questionnaire. Venous blood samples were withdrawn. Serum 25-OHD level was measured by using direct competitive chemiluminescence immunoassay. Vitamin D status was categorized as deficient (<20ng/ml), insufficient (21-29ng/ml) and sufficient (≥30ng/ml). The mean±SD level of 25-OHD was 14.76±7.03 ng/ml. The subjects with vitamin D deficiency, insufficiency and sufficiency were 83.8%, 11.4% and 4.8%, respectively suggestive of significant Vitamin D deficiency in high altitude Lahaul & Spiti district, Himachal Pradesh. [ABSTRACT FROM AUTHOR]

Our earlier studies both in animals and in humans have indicated that micronutrients (folic acid, vitamin B12) and long‐chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), are interlinked in the one‐carbon cycle, which plays an important role in fetal ‘programming’ of adult diseases. The present study examines the levels of maternal and cord plasma fatty acids, maternal folate, vitamin B12 and homocysteine in healthy mothers at various time points during pregnancy and also examine an association between them. A longitudinal study of 106 normal pregnant women was carried out, and maternal blood was collected at three time points, viz., T1 = 16–20th week, T2 = 26–30th week and T3 = at delivery. Cord blood was collected at delivery. Fatty acids were estimated using a gas chromatograph. Levels of folate, vitamin B12 and homocysteine were estimated by the chemiluminescent microparticle immunoassay (CMIA) technology. Maternal plasma folate (P < 0.05), vitamin B12 (P < 0.01) and DHA (P < 0.05) levels were lowest, while maternal homocysteine levels were highest (P < 0.01) at T3. There was a negative association between maternal DHA and homocysteine at T2 (P < 0.05) and T3 (P < 0.01). There was a positive association between plasma DHA in maternal blood at T3 and cord blood. Furthermore, there was a positive association between maternal folate and vitamin B12 at T3 and baby weight, whereas maternal homocysteine at T1 were inversely associated with baby weight at delivery. Our study provides evidence for the associations of folic acid, vitamin B12, homocysteine with DHA and baby weight, suggesting that a balanced dietary supplementation of folate–vitamin B12–DHA during pregnancy may be beneficial. [ABSTRACT FROM AUTHOR]

Background: Lipid quantity and quality have been shown to affect serum cholesterol, adipose and serum leptin levels during prenatal and postnatal dietary supplementation of adult rats. Maternal protein deficiency during pregnancy and lactation also affects polyunsaturated fatty acid (PUFA) levels in the offspring. The aim of the present study was to analyze the effect of α-linolenic acid (ALA; n-3) on n-3 PUFA accretion, lipid profile, leptin levels and adipose growth in normal and protein-restricted (deficient) dams and their suckling pups. Methods: Garden cress oil rich in ALA (32 %) was supplemented in the normal and protein-restricted (10 %) diets and fed to rats for 8 weeks prior to gestation and during lactation. PUFA, cholesterol, triglycerides, leptin levels and retroperitoneal white adipose tissue weight (WAT) of the dams and the pups were analyzed at 3 weeks after delivery. Results: The serum cholesterol levels were remarkably decreased ( p < 0.01), and the n-3 PUFA levels were markedly increased ( p < 0.05) in the pups of lactating normal and protein-deficient dams supplemented with ALA. Triglycerides were unaltered in the dams and the pups of different dietary groups. Serum leptin levels and relative WAT weights were lower ( p < 0.01) in the pups of the ALA-supplemented normal and protein-deficient dams. Conclusion: Maternal supplementation of ALA in normal and protein-restricted diets modulates n-3 PUFA levels, cholesterol, leptin levels and also adipose growth in the suckling offspring. [ABSTRACT FROM AUTHOR]

Background: The present study addressed the interesting findings of supplemental evaluation of hepatitis B “seroyield” donors. Materials and Methods: Each blood donor sample was tested for anti-human immunodeficiency virus type I (HIV-I)/HIV type II (HIV-II), HBsAg, and anti-hepatitis C virus (HCV) antibody by enhanced chemiluminescence method and subjected to individual donor-nucleic acid testing (NAT) for HIV-I, hepatitis B virus (HBV), and HCV. NAT test was performed using the eSAS system, Procleix Ultrio Assay, Novartis Diagnostics, CA, US. Confirmation of HBsAg was done using HBsAg Confirmatory Kit (Ortho Clinical Diagnostics, Johnson & Johnson, USA) and viral load assessment was done using Cobas TaqMan real time-polymerase chain reaction (RT-PCR) assay (Roche Molecular Systems, Branchburg, NJ, USA). To provide information on the stage of infection, specimens were tested for anti-HBc total (IgG + IgM), anti-HBc IgM and HBeAg. HBeAg-negative samples were tested for anti-HBe antibody. Results: A total of 60 hepatitis B seroyield donors which showed mean initial sample/cutoff of 1.6 with enhanced chemiluminescence assay were investigated further for confirmation of disease status. All 60 cases were confirmed positive with neutralization assay (VITROS HBsAg Confirmatory Kit) while no target was detected on viral load assessment with RT-PCR. Sixteen donors were HBeAg positive (4 IgM anti-HBc positive and 12 IgM anti-HBc negative) and 44 were IgM anti-HBc negative, anti-HBc total positive, and anti-HBe positive. Conclusion: About 7.7% of HBsAg positive and NAT nonreactive donors (nondetectable HBV DNA) could be potentially infectious (HBeAg positive), whereas rest of the donors were consistent with chronic HBV infection. [ABSTRACT FROM AUTHOR]

Introduction: Lab-diagnosis of hepatitis C virus (HCV) is based on detecting specific antibodies by enzyme immunoassay (EIA) or chemiluminescence immuno-assay (CIA). Center for Disease Control reported that signal-to-cut-off (s/co) ratios in anti-HCV antibody tests like EIA/CIA can be used to predict the probable result of supplemental test; above a certain s/co value it is most likely to be true-HCV positive result and below that certain s/co it is most likely to be false-positive result. A prospective study was undertaken in patients in tertiary care setting for establishing this “certain” s/co value. Materials and Methods: The study was carried out in consecutive patients requiring HCV testing for screening/diagnosis and medical management. These samples were tested for anti-HCV on CIA (VITROS® Anti-HCV assay, Ortho-Clinical Diagnostics, New Jersey) for calculating s/co value. The supplemental nucleic acid test used was polymerase chain reaction (PCR) (Abbott). PCR test results were used to define true negatives, false negatives, true positives, and false positives. Performance of different putative s/co ratios versus PCR was measured using sensitivity, specificity, positive predictive value and negative predictive value and most appropriate s/co was considered on basis of highest specificity at sensitivity of at least 95%. Results: An s/co ratio of ≥6 worked out to be over 95% sensitive and almost 92% specific in 438 consecutive patient samples tested. Conclusion: The s/co ratio of six can be used for lab-diagnosis of HCV infection; those with s/co higher than six can be diagnosed to have HCV infection without any need for supplemental assays. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Although TSH measurement by electrochemiluminescence immunoassay has become commonplace in India, significant discrepancy has been observed on interpretation of the test results when the manufacturer supplied biological reference interval (BRI) criteria were applied. This report determined whether the manufacturer's BRI (Roche Cobas) is transferable to the Indian population. Methods: Three hundred seventy-eight age- and sex-matched healthy subjects were selected from an urban Indian population. TSH reference measurements were acquired, and the reference data were statistically analysed. Results: BRI of the Indian urban reference population was determined by non-parametric means. BRI was found to be 1.134 to 7.280μIU/ml. Conclusion: BRI thus calculated was found to be significantly different from that mentioned by the manufacturer (0.27 to 4.20μIU/ml), which, needless to mention, has profound clinical implications in this part of the globe. [Copyright &y& Elsevier]

Objectives: There is no literature available on the performance of cystatin C in Chronic Kidney Disease (CKD) patients of Indian population based on age group. Hence, this study is aimed to compare the diagnostic performance of serum cystatin C and creatinine with measured glomerular filtration rate (GFR) and estimated GFR (eGFR) in subjects of Indian origin. Methods: The study was carried out at Tiruchirappalli, South India during the period of September 2010 to march 2011. One hundred and six CKD patients (82 males, 24 females) were enrolled and categorized into three groups based on age. The eGFR was calculated using Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) formulae. Serum cystatin C was measured with a particle-enhanced nephelometric immunoassay (PENIA) method. GFR was measured using 99mTC - diethylene triamine penta aceticacid (DTPA) renal scan method. Results: Serum cystatin C showed significant correlation with measured GFR in all the three groups (r=-0.9735, r=-0.8975 and r=-0.7994 respectively) than serum creatinine (r=-0.7380, r=- 0.6852 and r=-0.5127 respectively). Conclusion: Serum cystatin C showed a high correlation with measured GFR in young and older patients with CKD than creatinine. Thus, cystatin C is a good alternative marker to creatinine in CKD patients. [ABSTRACT FROM AUTHOR]

Polymorphisms in the drug transporter gene (ABCB1) may play a significant role in individualizing cyclosporine (CsA) and tacrolimus (Tac) dosage and subsequently the allograft outcome in renal transplant recipients. In total, 225 recipients on CsA and 75 on Tac-based immunosuppression regimen were recruited, and 6 common polymorphic sites in the ABCB1 gene were analyzed for association with dose-adjusted levels of CsA/Tac. Furthermore, association of ABCB1 single-nucleotide polymorphisms (SNPs) with allograft outcome was examined. GG and CC genotype patients at ABCB1 2677G>T and ABCB1 3435C>T were associated with lower dose-adjusted levels of CsA and Tac at 1 month (P = .057, P = .034), 3 months (P = .001, P = .015), and 6 months (P = .043) posttransplantation. Wild-type patients at 1236C>T (log P = .025) and 2677G>T (log P = .002) in CsA and 2677G>T (log P = .008) and 3435C>T (log P = .015) in Tac therapy patients demonstrated lower mean time to allograft rejection. No influence of ABCB1 haplotypes on CsA/Tac dose-adjusted levels was observed. Wild-type patients at ABCB1 2677G>T and 3435C>T were associated with lower dose-adjusted levels and thereby were at increased risk of allograft rejection because of under-immunosuppression in the early part of posttransplantation. Thus, genetic evaluation may be helpful to identify patients at risk for allograft rejection and also to individualize immunosuppressant dosing. [ABSTRACT FROM PUBLISHER]

Ethnopharmacological relevance: Emblica officinalis fruit (EO), commonly known as Amla is a reputed traditional medicine and functional food used in Indian subcontinent. It has long been used in Indian folk medicine to treat liver diseases, stomach ulcers, inflammatory diseases, metabolic disorders, geriatric complaints, skin disorders and beauty care. Aim of the study: Recently, it has been shown to promote pro-collagen content and inhibit matrix metalloproteinase levels in skin fibroblast. The aim of the present study was to investigate the efficacy of EO to inhibit UVB-induced photo-aging in human skin fibroblasts. Materials and methods: Mitochondrial activity of human skin fibroblasts was measured by MTT-assay. Quantifications of pro-collagen 1 and matrix metalloproteinase 1 (MMP-1) release were performed by immunoassay techniques. Hyaluronidase inhibition assay was studied in vitro using bovine testicular hyaluronidase and human umbilical cord hyaluronic acid. Cell cycle analysis was performed by flowcytometry using propidium iodide. Results: EO stimulated, the otherwise UVB inhibited cellular proliferation and protected pro-collagen 1 against UVB-induced depletion via inhibition of UVB-induced MMP-1 in skin fibroblasts (10–40μg/mL, p >0.001). EO exhibited inhibitory activity of hyaluronidase (10–40μg/mL, p >0.001). Treatment with EO also prevented UVB disturbed cell cycle to normal phase. Conclusion: The results of the present study suggests that EO effectively inhibits UVB-induced photo-aging in human skin fibroblast via its strong ROS scavenging ability and its therapeutic and cosmetic applications remain to be explored. [Copyright &y& Elsevier]

Aim of the study The present study investigated the influence of Clomipramine (Clmp) on male rat's sexual behavior, histology of testes and serum testosterone concentration. Material and Methods The study was conducted on male Sprague-Dawley rats in four groups of 12 rats each. Group I served as control and the therapeutic dose of 27mg/kg was given to Group II, III and IV as half therapeutic dose (½TD), therapeutic dose (TD) & double the therapeutic dose (2TD) of Clmp respectively. Sexual behavior of male rats was studied on 0, 15th, 30th & 60th days by challenging them with female rats in estrous phase. After 30 days treatment, blood samples were collected from half of the animals in each group and sacrificed, remaining animals on 60th day. Testes were collected and processed for histopathological examination. Serum separated and stored at -200C for testosterone estimation. Results and Conlusions Our study indicated that Clmp produced dose & time dependent sexual dysfunction. It also showed that ½TD of Clmp impaired the sexual behavior without decreasing the testosterone levels, TD & 2TD of Clmp produced sexual dysfunction and also decreased the serum testosterone levels and testicular cells count. Reduction in percentage of rats mounted, intromitted and ejaculated was observed dose and time dependently in all the doses of Clmp tested. All the latencies like mount latency, intromission latency, ejaculation latency and post ejaculatory pause were increased with all the doses of Clmp. Significant fall in testosterone was observed in TD and 2TD at the end of 30 days and 60 days. Reduction in testicular cell count was observed in ½TD, TD, 2TD after 30 days and further decline was observed at the end of 60 days treatment. However this was significant in TD and 2TD treatment groups. [ABSTRACT FROM AUTHOR]

Background: The pollen grain of the Areca catechu L. tree is airborne and allergenic. This study aimed to know the role of this pollen as a source of aeroallergen with effect on emergency asthma hospitalization, to isolate its important allergic fraction and to check its cross-reaction with betel nut. Methods:Areca pollen was monitored with a Burkard sampler. Determination of allergenic activities was studied by in vivo and in vitro analyses. Asthma hospitalization data were collected from two nearby hospitals. The pollen extract was fractionated by a combination of DEAE-Sephadex and Sephacryl S-200 column. The protein components were observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Cross-reactivity of Areca pollen and betel nut was shown by IgE enzyme-linked immunosorbent assay (ELISA) inhibition. Results: The Areca pollen was perennially airborne. Skin test results of respiratory allergic patients showed 38.6% positivity. The detected aeroallergen spots in particle immunoblotting correlated significantly with airborne pollen count. Areca pollen showed a significant positive correlation with asthma hospitalization. There are 6 IgE-reactive protein components in the whole-pollen extract. IgE-reactive fraction 1 was resolved into 4 subfractions. Subfraction 1a showing IgE reactivity contained 3 protein components, among which 2 of 48 and 118 kDa were IgE reactive. The 48-kDa component was reported to be cross-reactive with other palm pollen types. In IgE ELISA inhibition, the betel nut extract showed 50% inhibition with about 110 ng/ml concentration. Conclusion:A. catechu pollen is a significant contributor to the aeroallergen load in India. Its partially purified IgE-reactive fraction may be useful in therapeutics. The betel nut extract showed remarkable cross-reactivity with Areca pollen. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Deficiency in cystathionine beta synthase (CBS) enzyme sometimes leads to hyperhomocysteinemia/homocystinuria, conditions often associated with mental retardation (MR). In this investigation, association of idiopathic MR (IMR) with six CBS gene polymorphisms and fasting total plasma homocysteine (plHcy) was explored. Nuclear families with IMR probands (N =180) and control subjects (N =106) were recruited. Genomic DNA was subjected to PCR amplification and RFLP analysis. plHcy was measured by enzyme immunoassay. Data obtained was subjected to statistical analyses. Linkage disequilibrium between polymorphic sites was computed. T833C/844ins68 polymorphism revealed significant maternal transmission in IMR cases. The 31bpVNTR 21 repeat allele was significantly higher in male IMR cases as compared to sex-matched controls (P =0.004). A significant difference was also noticed in genotype frequencies of male IMR cases (P =0.005). Four other sites, G919A, C1105T, G1316A and G1330A, were not polymorphic in the studied population. While no significant contribution of any particular genotype was observed, plHcy level was significantly higher in male IMR cases as compared to sex-matched controls (P =0.0001). The data presented here is probably indicative of a higher risk of IMR in male subjects in association with two CBS polymorphisms and mild elevation in plHcy concentration. [Copyright &y& Elsevier]

Background: Lentils are the most common legume involved in allergic reactions in the Mediterranean area and India. Lentil crops could be attacked by a wide range of insect species. Occupational asthma caused by the lentil pest Bruchus lentis has been described in the present study. Objective: We studied the possibility of immunoglobulin (Ig)E-mediated hypersensitivity to lentil pests in 16 patients who suffered from allergic symptoms (asthma and anaphylaxis) related to inhalation of lentil particles or ingestion of lentils, in which sensitization to legume proteins was not clear. Methods: Extracts prepared either from noninfested and infested lentils, and from the lentil parasite B. lentis were used for skin prick testing (SPT), bronchial and oral challenges and in vitro determinations. Results: Skin prick test were positive to infested lentils and B. lentis in all patients and negative to noninfested lentil extracts. Five asthmatic patients reacted in the bronchial challenge test with Bruchus extract. Oral challenges performed with boiled infested lentils were positive in six of seven patients. Immunoglobulin E immunoblotting with Bruchus and infested lentils extracts revealed protein bands that were reactive to serum IgE from six and four, respectively, out of 16 patients. These patients had no IgE to lentil-specific proteins as determined by immunoblotting and Len c 1-specific IgE test. Conclusions: Lentil pest proteins can be a cause of IgE-mediated rhinoconjunctivitis and asthma in patients eating or inhaling infested lentil particles. [ABSTRACT FROM AUTHOR]

• The prevalence of melioidosis in patients presenting with sepsis without CAP, with sepsis and underlying CAP, with only CAP without sepsis was 31%, 22% and 3 % respectively. • All the LFI or PCR positive cases were culture positive from at least one or more samples (blood/sputum/urine/pus). • The sensitivity, specificity, positive predictive value and negative predictive value of TTS1 PCR was 78% (18/23 melioidosis patients), 100% (34/34 non-melioidosis patients), 100% (18/18 melioidosis patients) and 87% (34/39 non-melioidosis patients). • The sensitivity, specificity, positive predictive value and negative predictive value of Rapid LFI was 91% (21/23 melioidosis patients), 100% (22/22 non-melioidosis patients), 100% (21/21 melioidosis patients) and 91% (22/24 non-melioidosis patients). • On sample wise stratification of LFI and TTS1 with respect to culture, plasma/serum samples showed the highest discordance by PCR (9/55, 16%) and LFI (11/35, 31%), with respect to culture. The lowest discordance was noted in respiratory tract samples (2/32, 6%) by PCR and pus/body fluids samples (2/14, 14%) by LFI. • The clinical utility of PCR and LFI needs to be further validated in a large scale study for early diagnosis of septicaemic melioidosis. Establishing a diagnosis of melioidosis based on clinical grounds is difficult in hospitalized patients with sepsis or community acquired pneumonia (CAP). We aimed to ascertain the prevalence, clinico-epidemiological and laboratory profile of melioidosis in hospitalized patients with sepsis or CAP, and to evaluate the diagnostic utility of rapid lateral flow immunoassay (LFI) and PCR in comparison with culture. In all patients with sepsis or CAP, blood, sputum/throat swab, and urine sample were subjected to culture along with other samples based on clinical presentation. In addition, PCR assay targeting the type III secretion system 1 (TTS1) and LFI was performed. Thirty-three (33/196, 17%) out of the total 196 cases were diagnosed as melioidosis by culture. The prevalence of melioidosis in patients who had only sepsis without CAP, had both sepsis and CAP, had CAP without sepsis was 31% (26/84), 22 % (4/18) and 3%(3/94) respectively. All the LFI or PCR positive cases were culture positive from at least one or more samples (blood/sputum/urine/pus). The sensitivity, specificity, positive predictive value and negative predictive value of TTS1 PCR was 78% (18/23 melioidosis patients), 100% (34/34 non-melioidosis patients), 100% (18/18 melioidosis patients) and 87% (34/39 non-melioidosis patients). The sensitivity, specificity, positive predictive value and negative predictive value of Rapid LFI was 91% (21/23 melioidosis patients), 100% (22/22 non-melioidosis patients), 100% (21/21 melioidosis patients) and 91% (22/24 non-melioidosis patients). On sample wise stratification of LFI and TTS1 with respect to culture, plasma/serum samples showed the highest discordance by PCR (9/55, 16.3%) and LFI (11/35, 31.4%). The lowest discordance was noted in respiratory tract samples (2/32, 6.2%) by PCR and pus/body fluids samples (2/14, 14.2%) by LFI and these findings are in line with previous published literature. The clinical utility of PCR and LFI needs to be further validated in a large scale study for early diagnosis of septicaemic melioidosis. [ABSTRACT FROM AUTHOR]

• rPPRV-NPN-specific polyclonal antibodies based ABrAC ELISA developed for surveillance of PPR. • Assay is rapid, sensitive, and specific for the detection of the PPR virus/antigens in the clinical specimens. • rPPRV-NPN and its polyclonal antibodies could be the sustainable source of safe diagnostic reagents in ABrAC ELISA. This study describes the development of Avidin-Biotin recombinant Antigen Capture ELISA (ABrAC ELISA) for the detection of the peste des petits ruminants virus (PPRV) antigens in the clinical specimens of sheep and goats. The assay uses the truncated recombinant PPRV N-terminal immunogenic region of nucleoprotein (rPPRV-NPN) as a reference positive antigen and its polyclonal antibodies as capture/detective antibodies and the rabbit PPRV polyclonal antibodies as coating antibodies. The cut-off value was determined as double times the mean reactivity of blank control based on the reactivity of the PPR confirmed negative and positive control panel samples. On assessing the specificity with the related differential diagnosis of the disease-causing viruses and bacteria, the assay showed specific detective reactivity to PPRV. Further, on evaluation using clinical specimens (n-274) of sheep and goats, the assay showed that the relative diagnostic sensitivity of 86.49 % (95 % confidence interval (CI): 71.23–95.46 %) and diagnostic specificity of 96.20 % (95 % CI: 92.91–98.25 %) against PPRV nucleoprotein-specific monoclonal antibody-based sandwich-ELISA (PPR s-ELISA) kit, with an accuracy of 94.89 % (95 % CI: 91.58–97.18 %) and Cohen's Kappa value of 0.791 + 0.055 SE (95 % CI: 0.68−0.90) with substantial agreements. The ABrAC-ELISA is an alternative method of an immunoassay for the rapid, sensitive, and specific detection of the PPRV antigens m the clinical specimens of sheep and goats for surveillance or diagnosis of PPR. This study also shows that the rPPRV-NPN and its specific polyclonal antibodies could be the sustainable source of safe diagnostic reagents without the need to handle the infectious virus during the eradication and post-eradication phases in endemic countries like India or PPR non-endemic countries. [ABSTRACT FROM AUTHOR]

IgG immunoassays have been developed and used widely for clinical samples and serosurveys for SARS-CoV2, with most detecting antibodies against the spike/receptor-binding-domain or nucleocapsid. Limited information is available on comparative evaluation of IgG immunoassays against a clinical reference standard, i.e., RT-PCR positivity with >20 days of illness. This study addresses the need for comparing clinical performance of IgG immunoassays with respect to this alternate reference standard. We compared the performance of three immunoassays, an in-house RBD assay, and two commercial assays, the Diasorin LIAISON SARS-CoV-2 S1/S1 IgG CLIA which detects antibodies against S1/S2 domains of the Spike protein and the Zydus Kavach assay based on inactivated virus using a well-characterized panel of sera. 379 sera and plasma samples from RTPCR positive individuals >20 days of illness in symptomatic or RT-PCR positivity in asymptomatic individuals and 184 samples collected prior to 2019 were used for assay evaluation. The sensitivity of the assays were 84.7 (95 %CI 80.6–88.1), 82.6 (95 %CI 78.3–86.2) and 75.7 (95 %CI 71.0–79.9) respectively for RBD, LIAISON and Kavach. Kavach and the in-house RBD ELISA showed a specificity of 99.5 % and 100 %, respectively. The RBD and LIAISON (S1/S2) assays showed high agreement (94.7 %; 95 %CI: 92.0, 96.6) and were able to correctly identify more positive sera/plasma than Kavach. Independent comparisons support the evaluation of performance characteristics of immunoassays. All three assays are suitable for serosurveillance studies, but in low prevalence sites, estimation of exposure may require adjustment based on our findings. [ABSTRACT FROM AUTHOR]

• A microsphere‐based immunoassay developed for glanders • Hcp1 and GroEL antigens exhibited the best specificity and sensitivity Burkholderia mallei is the etiologic agent of glanders, an infectious disease of solipeds, with renewed scientific interest due to its increasing incidence in different parts of the world. More rapid, sensitive and specific assays are required by laboratories for confirmatory testing of this disease. A microsphere‐based immunoassay consisting of beads coated with B. mallei recombinant proteins (BimA, GroEL, Hcp1, and TssB) has been developed for the serological diagnosis of glanders. The proteins' performance was compared with the OIE reference complement fixation test (CFT) and an indirect enzyme‐linked immunosorbent assay (iELISA) on a large panel of sera comprised of uninfected horses (n=198) and clinically confirmed cases of glanders from India and Pakistan (n=99). Using Receiver Operating Characteristics (ROC) analysis and adjusting the cutoff levels, Hcp1 (Se=100%, Sp=99.5%) and GroEL (Se= 97%, Sp=99.5%) antigens exhibited the best specificity and sensitivity. Neither Hcp1 and GroEL proteins, nor iELISA reacted with doubtful and positive CFT samples from glanders free countries which further confirmed the false positive reactions seen in CFT. [ABSTRACT FROM AUTHOR]

Background & Objectives: Healthcare workers (HCWs) are considered to be at a high risk of contracting COVID-19 infection. Besides, control of nosocomial infections transmitted from HCWs to the patients is also a cause of concern. This study was undertaken to investigate the seroprevalence of antibodies against the SARS-CoV-2 virus among the hospital staff of a tertiary care health facility in north India., Methods: The HCWs were tested for SARS-CoV-2 serology (IgG+IgM) using chemiluminescence immunoassay between June 22 and July 24, 2020. Venous blood (2 ml) was collected and tested for SARS-CoV-2 IgG and IgM antibodies., Results: Of the 3739 HCWs tested, 487 (13%) were positive for total SARS-CoV-2 antibodies. The highest seroprevalence was observed in administrative staff (19.6%) and least in physicians (5.4%). The staff who used public (20%) and hospital transportation (16.9%) showed higher seroprevalence compared to staff using personal transportation (12.4%). No difference was observed between HCWs posted in COVID versus non-COVID areas. All seropositive symptomatic HCWs in our study (53.6%) had mild symptoms, and the remaining 46.4 per cent were asymptomatic. The antibody positivity rate progressively increased from 7.0 per cent in the first week to 18.6 per cent in the fourth week during the study., Interpretation & Conclusions: The presence of antibodies to SARS-CoV-2 in a significant number of asymptomatic HCWs, association with the use of public transport, relatively lower seroprevalence compared with the non-HCWs and rising trend during the period of the study highlight the need for serosurveillance, creating awareness for infection control practices including social distancing and study of infection dynamics in the community for effective control of an infectious pandemic., Competing Interests: None

Background & Objectives: Coronavirus disease 2019 (COVID-19) has so far affected over 41 million people globally. The limited supply of real-time reverse transcription-polymerase chain reaction (rRT-PCR) kits and reagents has made meeting the rising demand for increased testing incompetent, worldwide. A highly sensitive and specific antigen-based rapid diagnostic test (RDT) is the need of the hour. The objective of this study was to evaluate the performance of a rapid chromatographic immunoassay-based test (index test) compared with a clinical reference standard (rRT-PCR)., Methods: A cross-sectional, single-blinded study was conducted at a tertiary care teaching hospital in north India. Paired samples were taken for RDT and rRT-PCR (reference standard) from consecutive participants screened for COVID-19 to calculate the sensitivity and specificity of the RDT. Further subgroup analysis was done based on the duration of illness and cycle threshold values. Cohen's kappa coefficient was used to measure the level of agreement between the two tests., Results: Of the 330 participants, 77 were rRT-PCR positive for SARS-CoV-2. Sixty four of these patients also tested positive for SARS-CoV-2 by RDT. The overall sensitivity and specificity were 81.8 and 99.6 per cent, respectively. The sensitivity of RDT was higher (85.9%) in participants with a duration of illness ≤5 days., Interpretation & Conclusions: With an excellent specificity and moderate sensitivity, this RDT may be used to rule in COVID-19 in patients with a duration of illness ≤5 days. Large-scale testing based on this RDT across the country would result in quick detection, isolation and treatment of COVID-19 patients., Competing Interests: None

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted (at the time of writing) in over 3.3 million cases and 233,000 deaths globally and ~33,000 cases and ~1,100 deaths in India. The mainstay of the diagnosis is a reverse-transcription polymerase chain reaction assay to detect SARS-CoV-2 RNA. The accurate diagnosis is contingent on appropriate specimen choice, time of collection, and assay employed. In this commentary, we highlight the role of laboratory diagnostic tests used in the different stages of India's COVID-19 pandemic response., Competing Interests: None

Aim: To evaluate validate and analyse Luminex – X Map technology for detection of donor specific antibodies (DSA) and panel reactive antibody (PRA) screen in a standalone laboratory in India. Methods: Thirty –two samples and 22 controls were evaluated for presence of Class I and II DSA using of IgG isotype using Genprobe (USA) kits. B and T cell crossmatch had been performed on all samples by two stage basic NIH method on all samples. PRA screen was performed on 35 samples with inclusion of positive and negative controls in each of the three assays using commercial kits from the same vendor. Reproducibility in PRA screen testing was checked on eight samples of which three samples were tested in triplicate and five samples in duplicate. DSA was also carried out on five samples in duplicate. Results: Data accrued from validation studies are shown in Table 1. High background was observed in 20 and 10 percent of the samples for DSA and PRA respectively. The background was reduced by 35-60% on using Seraclean. The overall results were unaffected by high background. Results of PRA were concordant in 90 % of samples for class I DSA and PRA. Conclusions: DSA and PRA screen detected class II antibodies in far more cases than class I antibodies and both tests may be used for detection of antibodies which may be missed on serology.[Table 1] [Copyright &y& Elsevier]

Background: The Ortho ECi assay employs an immunometric technique with enhanced chemiluminiscence for optimal assay performance. The performance of a fully automated, randomaccess, enhanced chemiluminiscence immunoassay (Ortho ECi) for the detection of HBsAg, anti-HIV and anti-HCV in the serum of blood donors was evaluated at Department of Transfusion Medicine, SPS Apollo Hospitals, Ludhiana, for a period of 14 months (June 2005 to August 2006). Aims: To evaluate the working of Ortho ECi for routine screening of blood donors. Materials and Methods: 2341 samples were processed on Ortho ECi system for all three parameters. The reactive samples were re-run on the same system. Repeat reactive samples were then sent for confirmation at the Ortho Diagnostic.s reference laboratory. Results: The overall concordance between the Ortho ECi assays for HBsAg, anti HIV and anti HCV and the corresponding confiiniatory tests was 100%, 99.8% and 99.8% respectively. The specificities of the assays for HBsAg, anti HIV and anti HCV were 100%, 99.9% and 99.8% respectively. The sensitivities of the assays for HBsAg, anti HIV and anti HCV were 100%, 100% and 100% respectively. The Positive Predictive values (PPV) of the assays for HBsAg, anti HIV and anti HCV were 100%, 33% and 85% respectively. The Negative Predictive values (NPV) of the assays for HBsAg, anti HIV and anti HCV were 100%, 100% and 100% respectively. Conclusions: The Ortho ECi assays for diagnosis of HBsAg, anti- HIV and anti-HCV are highly specific and sensitive assays. The rapid turn around time (TAT), random access, full automation and high throughput make it an effective assay system for blood bank screening programmes for blood donors, thus increasing the patient safety. The instrument has an additional advantages of intellicheck feature, closed system, capability of processing STAT samples and being user friendly with touch-screen. [ABSTRACT FROM AUTHOR]