Analytical and Clinical Performance of Two Point of Care Rapid Antibody Assays for SARS-CoV-2.

OBJECTIVE: The SARS-CoV-2 pandemic has reached to a state where populations across the world should ad-just to live with it like many other diseases. Regular serosurveys are essential for disease surveil-lance and policy decisions. In this study, we evaluated the analytical and clinical performance of two commercially available rapid antibody assays. METHODS: SARS-CoV-2 PCR positive patients (N=104) were recruited for method evaluation study of two commercially available lateral flow Rapid IgM and IgG assays; Edinburgh Genetics ActivXpress+ COVID-19 IgG/IgM Immunoassay Complete Testing Kit (EGCV0092L) and Abchek COVID-19 IgM/IgG Antibody Rapid Test (NUL/COV-19/R&D/001). We have tested all the participants for SARS-CoV-2 with a Rapid Anti-gen Test (Abchek) on the day of sample collection. Additionally, we analyzed vaccinated people (N=187) for seroprevalence of IgG. EP Evaluator version 12 and GraphPad Prism 9.5.0 were used for statistical analysis. RESULTS: The IgG seropositivity after 10-15 days of PCR positivity was 97.11% (Edinburg Genetics Assay) and 92.30% (Abchek Assay). The Rapid Antigen test was 100% negative with IgM negativity of 93.27% (Edinburg Genetics Assay) and 98.08% (Abchek Assay). The IgG seropositivity of vaccinated participants was 89.84% using both the assays. The IgG sero-positivity was 86.82% (Edinburg Genetics Assay, N=91) and 92.71% (Abchek Assay, N=96) in the study participants with post vaccination. CONCLUSIONS: These assays are robust and scalable. Both the assays can be used for serosurveys with desired scale and speed when a quick observation is needed for surveillance. These tests are cost effective, field deployable without need of any sophis-ticated instruments and large capital. IMPACT STATEMENT: During a public health emergency like the COVID-19 pandemic, regular sero-surveys are essential for disease surveillance and swift policy decisions. However, deployment of the gold standard methods like quantitative ELISA, neutralizing antibody assays for assessment of population based seroprevalence and immune status becomes logistically difficult, costly and time consuming. The point of care antibody assays are easily scalable, affordable and field deployable. The present study demonstrates that these tests are reliable in terms of analytical and clinical performance. These assays could be used when rapid observations are to be made by including large sample population.

The GSTM1 and GSTT1 Null Genotypes Increase the Risk for Type 2 Diabetes Mellitus and the Subsequent Development of Diabetic Complications: A Meta-analysis.

BACKGROUND: Studies pertaining to association of GSTM1 and GSTT1 null genotypes with risk of T2DM and its complications were often inconclusive, thus spurring the present study. METHODS: Meta-analysis of 25 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in determining the risk for T2DM and 17 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in development of T2DM related complications were conducted. RESULTS: Our study revealed an association between GSTM1 and GSTT1 null polymorphism with T2DM (GSTM1; OR=1.37;95% CI =1.10-1.70 and GSTT1; OR=1.29;95% CI =1.04-1.61) with an amplified risk of 2.02 fold for combined GSTM1-GSTT1 null genotypes. Furthermore, the GSTT1 null (OR=1.56;95%CI=1.38-1.77) and combined GSTM1-GSTT1 null genotypes (OR=1.91;95%CI=1.25- 2.94) increased the risk for development of T2DM related complications, but not the GSTM1 null genotype. Stratified analyses based on ethnicity revealed GSTM1 and GSTT1 null genotypes increase the risk for T2DM in both Caucasians and Asians, with Asians showing much higher risk of T2DM complications than Caucasians for the same. DISCUSSION: GSTM1, GSTT1 and combined GSTM1-GSTT1 null polymorphism may be associated with increased risk for T2DM; while GSTT1 and combined GSTM1-GSTT1 null polymorphism may increase the risk of subsequent development of T2DM complications with Asian population carrying an amplified risk for the polymorphism. CONCLUSION: Thus GSTM1 and GSTT1 null genotypes increases the risk for Type 2 diabetes mellitus alone, in combination or with regards to ethnicity.

A murine model of type 2 diabetes mellitus developed using a combination of high fat diet and multiple low doses of streptozotocin treatment mimics the metabolic characteristics of type 2 diabetes mellitus in humans.

INTRODUCTION: A murine model of type 2 diabetes mellitus was used to compare the antidiabetic effects of the dipeptidyl peptidase-4 (DPP4) inhibitor vildagliptin and biguanide, metformin. METHODS: Swiss albino mice (n=20 males; n=25 females) were given high fat diet (HFD) ad libitum for 3weeks followed by low dose (40mgkg-1 body weight, bw daily) of streptozotocin (STZ) intraperitoneally five times from the 22nd day of treatment onwards, with HFD continued up to 26th day. Controls (n=15 males; n=15 females) were fed normal balanced diet without administration of STZ. Successful induction of diabetes mellitus was confirmed by testing for fasting blood glucose, intraperitoneal glucose tolerance and intraperitoneal insulin sensitivity. Diabetic mice were administered vildagliptin (10mgkg-1 bw daily) and metformin (50mgkg-1 bw daily) orally for 4weeks. Control, diabetic, vildagliptin and metformin-treated diabetic mice were evaluated for alterations in lipid profile using blood serum and histopathology and oxidative stress using tissues including liver, kidney and heart. RESULTS: Diabetic mice showed significant alterations in lipid profile, tissue histopathology, impaired glucose tolerance, lower insulin sensitivity and elevated lipid peroxidation and protein carbonylation, with depressed catalase activity, when compared to age and gender-matched controls. Metformin and vildagliptin ameliorated the abovementioned diabetic conditions, with vildagliptin found to be more effective. DISCUSSION: A murine model developed by the combination of HFD and multiple low dose of STZ mimics the metabolic characteristics of type 2 diabetes mellitus in humans, and may be useful for antidiabetic drug screening.

Association between OGG1 Ser326Cys polymorphism and risk of upper aero-digestive tract and gastrointestinal cancers: a meta-analysis.

Cancers of the upper aero-digestive and gastrointestinal tract are one of the major causes of mortality around the world. DNA repair genes play a vital role in preventing carcinogenesis by maintaining genomic integrity. Polymorphisms in the nucleotide sequence of DNA repair genes are often reported to be associated with an increased risk for different cancers. The OGG1 gene encodes the enzyme 8-oxoguanine DNA glycosylase which removes oxidatively damaged bases of DNA. Several studies report that the OGG1 Ser326Cys polymorphism increases the risk for cancers of the upper aero-digestive and gastrointestinal tract. However, other studies provide evidence that such an association does not exist. A meta-analysis to assess the role of OGG1 Ser326Cys polymorphism in the cancers of the upper aero-digestive and gastrointestinal tract was therefore undertaken in order to resolve this ambiguity. Seventeen studies were recruited for this meta-analysis after screening 58 articles with a total of 5533 cases and 6834 controls for which the odds ratio with 95 % confidence interval was calculated. Begg's funnel test and Egger's test were performed for calculating publication bias. Our study reveals an association between OGG1 Ser326Cys polymorphism and cancer susceptibility of the upper aero-digestive and gastrointestinal tract (CG + GG vs CC; odds ratio, OR 1.22; 95 % CI 1.05-1.41; GG vs CG + CC; OR 1.36; 95 % CI 1.09-1.70; GG vs CC; OR 1.46; 95 % CI 1.12-1.92). Subgroup analysis based on cancer types and ethnicity also revealed the association of OGG1 Ser326Cys polymorphism to the risk for upper aero-digestive and gastrointestinal tract cancers among both the Asian and the Caucasian populations. No risk was however observed for smoking habits and OGG1 Ser326Cys polymorphism. In conclusion, OGG1 Ser326Cys polymorphism may be associated with the increased risk for aero-digestive tract and gastro-intestinal cancers in both Asian and Caucasian populations.

ATM rs189037 (G > A) polymorphism and risk of lung cancer and head and neck cancer: A meta-analysis.

A number of different epidemiological studies have measured the association between the risk of different cancers and polymorphism at promoter region of 5' untranslated region (5'-UTR) of the Ataxia-telangiectasia mutated (ATM) gene. However the results were contentious rather than conclusive. The current study was aimed at evaluating the association between the SNP (rs189037 G>A) and the risk of head and neck cancer and lung cancer by conducting a meta-analysis. A total of 9 case-control studies were considered for this quantitative analysis. Stats Direct Statistical software (version 2.7.2) was used to evaluate the crude odds ratio (OR) with their 95% confidence interval (CI). The dominant model (GG vs. GA + AA) showed no heterogeneity and the fixed effects pooled OR was found to be significant (OR = 1.14, 95% CI = 1.05-1.25) at p = 0.003. The pooled OR for fixed effects of heterozygote and homozygote mutant allele (GA vs. AA) model was significant (OR = 1.17, 95% CI = 1.04-1.30, p = 0.006) and no heterogeneity was observed for this model. The current meta-analysis manifested that ATM rs189037 G>A genetic polymorphism may contribute increased risk of head and neck and lung cancer. Moreover, the AA mutant allele was found to be related significantly with the prognosis of lung cancer and head and neck cancer.

MicroRNAs: a new ray of hope for diabetes mellitus.

Diabetes mellitus has become one of the most common chronic diseases, thereby posing a major challenge to global health. Characterized by high levels of blood glucose (hyperglycemia), diabetes usually results from a loss of insulin-producing ß-cells in the pancreas, leading to a deficiency of insulin (type 1 diabetes), or loss of insulin sensitivity (type 2 diabetes). Both types of diabetes have serious secondary complications, such as microvascular abnormalities, cardiovascular dysfunction, and kidney failure. Various complex factors, such as genetic and environmental factors, are associated with the pathophysiology of diabetes. Over the past two decades, the role of small, single-stranded noncoding microRNAs in various metabolic disorders, especially diabetes mellitus and its complications, has gained widespread attention in the scientific community. Discovered first as an endogenous regulator of development in the nematode Caenorhabditis elegans, these small RNAs post-transcriptionally suppress mRNA target expression. In this review, we discuss the potential roles of different microRNAs in diabetes and diabetes-related complications.