SARS-CoV-2 has surged across the globe causing the ongoing COVID-19 pandemic. Systematic testing to facilitate index case isolation and contact tracing is needed for efficient containment of viral spread. The major bottleneck in leveraging testing capacity has been the lack of diagnostic resources. Pooled testing is a potential approach that could reduce cost and usage of test kits. This method involves pooling individual samples and testing them ‘ en bloc ’. Only if the pool tests positive, retesting of individual samples is performed. Upon reviewing recent articles on this strategy employed in various SARS-CoV-2 testing scenarios, we found substantial diversity emphasizing the requirement of a common protocol. In this article, we review various theoretically simulated and clinically validated pooled testing models and propose practical guidelines on applying this strategy for large scale screening. If implemented properly, the proposed approach could contribute to proper utilization of testing resources and flattening of infection curve.

BackgroundThe early diagnosis of tuberculosis using novel non-sputum-based biomarkers is of high priority in the End TB strategy. MicroRNAs (miRNAs) are significant regulators of TB pathogenesis and their differential expression pattern among healthy, latent, and active TB population has revealed their potentiality as biomarkers in recent studies. Thus, we systematically reviewed and performed a meta-analysis on the role of host miRNAs in TB diagnosis. We also reviewed the involvement of miRNAs in the immune response to Mycobacterium tuberculosis (Mtb).MethodsPubmed, Ovid and Cochrane databases were searched to retrieve published literature from 2000 to 2020 using predefined keywords. We screened relevant studies based on inclusion and exclusion criteria and the included studies were assessed for their quality using STARD guidelines and QUADAS-2 tool. Funnel plots were constructed to assess the publication bias. The heterogeneity of studies and overall pooled results of sensitivity, specificity and DOR were determined using forest plots.ResultsWe retrieved a total of 447 studies collectively from all the databases, out of which 21 studies were included for qualitative analysis. In these studies, miR-29, miR-31, miR-125b, miR146a and miR-155 were consistently reported. The overall sensitivity, specificity and DOR of these miRNAs were found to be 87.9% (81.7-92.2), 81.2% (74.5-86.5) and 43.1(20.3-91.3) respectively. Among these, miR-31 had the maximum diagnostic accuracy, with a sensitivity of 96% (89.7-98.5), specificity of 89% (81.2-93.8) and DOR of 345.9 (90.2-1326.3), meeting the minimal target product profile (TPP) for TB diagnostics.ConclusionmiRNAs can thus be exploited as potential biomarkers for rapid detection of tuberculosis as evident from their diagnostic performance. Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021226559 PROSPERO (CRD42021226559).

The functional significance of the HIV-1 Antisense Protein (ASP) has been a paradox since its discovery. The expression of this protein in HIV-1-infected cells and its involvement in autophagy, transcriptional regulation, and viral latency have sporadically been reported in various studies. Yet, the definite role of this protein in HIV-1 infection remains unclear. Deciphering the 3D structure of HIV-1 ASP would throw light on its potential role in HIV lifecycle and host-virus interaction. Hence, using extensive molecular modeling and dynamics simulation for 200 ns, we predicted the plausible 3D-structures of ASP from two reference strains of HIV-1 namely, Indie-C1 (subtype-C) and NL4-3 (subtype-B) so as to derive its functional implication through structural domain analysis. In spite of sequence and structural differences in subtype B and C ASP, both structures appear to share common domains like the Von Willebrand Factor Domain-A (VWFA), Integrin subunit alpha-X (ITGSX), and ETV6-Transcriptional repressor, thereby reiterating the potential role of HIV-1 ASP in transcriptional repression and autophagy, as reported in earlier studies. Gromos-based cluster analysis of the centroid structures also reassured the accuracy of the prediction. This is the first study to elucidate a highly plausible structure for HIV-1 ASP which could serve as a feeder for further experimental validation studies.

Background The positive predictive value of Tuberculin Skin Test and current generation Interferon Gamma Release Assays are very low leading to high numbers needed to treat. Therefore, it is critical to identify new biomarkers with high predictive accuracy to identify individuals bearing high risk of progression to active tuberculosis. Methods We used stored QuantiFERON supernatants from 14 household contacts of index TB patients who developed incident active TB during a two-year follow-up and 20 age and sex-matched non-progressors. The supernatants were tested for an expanded panel of 45 cytokines, chemokines and growth factors using the Luminex Multiplex Array kit. Results We found significant differences in the levels of TB-antigen induced production of several analytes between progressors and non-progressors. Dominance analysis identified 15 key predictive biomarkers based on relative percentage importance. Principal component analysis revealed that these biomarkers could robustly distinguish between the two groups. Receiver operating characteristic analysis identified IP-10, CCL19, IFN-γ, IL-1ra, CCL3 and GM-CSF as the most promising predictive markers, with AUC ≥90. IP-10/CCL19 ratio exhibited maximum sensitivity and specificity (100%) in predicting progression. Through Classification and Regression Tree analysis, a cut-off of 0.24 for IP-10/CCL19 ratio was found to be ideal for predicting short-term risk of progression to TB disease with a positive predictive value of 100 (95% CI 85.8-100). Conclusion The biomarkers identified in this study will pave way for the development of a more accurate test that can identify individuals at high risk for immediate progression to TB disease for targeted intervention.

Chronic viral infections represent a leading cause of global morbidity and mortality. Chronic HBV, HCV, and HIV infections result in cytokine perturbations that may hold key implications in understanding the complex disease mechanisms driving virus persistence and/or resolution. Here, we determined the levels of various plasma cytokines using a commercial Bio-Plex Luminex cytokine array in chronic HBV (n = 30), HCV (n = 15), and HIV (n = 40) infections and correlated with corresponding plasma viral loads (PVLs) and liver parameters. We observed differential perturbations in cytokine profiles among the study groups. The cytokines levels positively correlated with PVL and liver transaminases. The monocyte-derived cytokines viz., MIP-1β, IL-8, and TNF-α, and Th2 cytokines like IL-4, IL-5, and IL-13 showed a better correlation with liver enzymes as compared to their corresponding PVLs. Our investigation also identified two cytokines viz., IL-5 and IL-7 that inversely correlated with HBV DNA and HIV PVLs, respectively. Regression analysis adjusted for age showed that every increase of IL-5 by one unit was associated with a reduction in HBV PVL by log10 0.4, whereas, every elevation by a unit of IL-7 was associated with decreased HIV PVL by log10 2.5. We also found that IL-7 levels correlated positively with absolute CD4+ T cell counts in HIV-infected patients. We concluded that plasma IL-5 and IL-7 may likely have a key role on viral control in HBV and HIV infections, respectively. A noteworthy increase in cytokines appears to bear protective and pathological significance, and indeed is reflective of the host’s versatile immune armory against viral persistence.

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Background: Diabetes is found to be one of the major causes for ocular disease such as retinopathy, cataract, and eye infections. Several studies in recent time focus on ocular function and tear function related to diabetes. This study is focused to find the differences in ocular tear function using Shirmer’s test and tear break-up time (TBUT) among three groups of people such as those who are normal, those with diabetes mellitus (DM) and the group of people having diabetic retinopathy (DR). Aims and Objectives: The aim of the study was to study the ocular tear function among normal subjects, patients with Type II diabetes mellitus, and among patients with DR and compare the results. Materials and Methods: A total of 90 participants were included in the study. Three different groups of population were selected such as the normal (30 respondents), DM (30 respondents), and DR (30 respondents). They were evaluated for their glycemic index using fasting, post-prandial, and HBA1C, by the researchers. An ocular fundus evaluation using 90 D biomicroscopy to select patients with DR was done. Two tests were used to study the ocular functions such as the TBUT test and Schirmer’s test. The data were entered in excel and analyzed with the help of SPSS 26. Statistical tests such as descriptive statistics, frequency and percentages, Chi-square, and Kruskal–Wallis were used. Results: The ocular tear film parameters, Schirmer’s test, and TBUT were significantly reduced in diabetic patients and those with DR when compared to control group. These results indicate that dry eye is a significant diabetic ocular surface disease feature. Conclusion: When compared with the control group, both the study groups (D.M. and D.R.) have a significant abnormality in the results of the Shirmer’s and TBUT tests. There is a strong association between diabetes control and ocular tear function tests and is proven that diabetic control has a highly significant influence on the ocular tear film function.

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