nSARS-Cov-2, pulmonary edema and thrombosis: possible molecular insights using miRNA-gene circuits in regulatory networks.

BACKGROUND: Given the worldwide spread of the novel Severe Acute Respiratory Syndrome Coronavirus 2 (nSARS-CoV-2) infection pandemic situation, research to repurpose drugs, identify novel drug targets, vaccine candidates have created a new race to curb the disease. While the molecular signature of nSARS-CoV-2 is still under investigation, growing literature shows similarity among nSARS-CoV-2, pulmonary edema, and thromboembolic disorders due to common symptomatic features. A network medicine approach is used to to explore the molecular complexity of the disease and to uncover common molecular trajectories of edema and thrombosis with nSARS-CoV-2. RESULTS AND CONCLUSION: A comprehensive nSARS-CoV-2 responsive miRNA: Transcription Factor (TF): gene co-regulatory network was built using host-responsive miRNAs and it's associated tripartite, Feed-Forward Loops (FFLs) regulatory circuits were identified. These regulatory circuits regulate signaling pathways like virus endocytosis, viral replication, inflammatory response, pulmonary vascularization, cell cycle control, virus spike protein stabilization, antigen presentation, etc. A unique miRNA-gene regulatory circuit containing a consortium of four hub FFL motifs is proposed to regulate the virus-endocytosis and antigen-presentation signaling pathways. These regulatory circuits also suggest potential correlations/similarity in the molecular mechanisms during nSARS-CoV-2 infection, pulmonary diseases and thromboembolic disorders and thus could pave way for repurposing of drugs. Some important miRNAs and genes have also been proposed as potential candidate markers. A detailed molecular snapshot of TGF signaling as the common pathway, that could play an important role in controlling common pathophysiologies among diseases, is also put forth. SUPPLEMENTARY INFORMATION: Supplementary information accompanies this paper at 10.1186/s41544-020-00057-y.

Prevalence of SARS-CoV-2 infection in India: Findings from the national serosurvey, May-June 2020.

BACKGROUND & OBJECTIVES: Population-based seroepidemiological studies measure the extent of SARS-CoV-2 infection in a country. We report the findings of the first round of a national serosurvey, conducted to estimate the seroprevalence of SARS-CoV-2 infection among adult population of India. METHODS: From May 11 to June 4, 2020, a randomly sampled, community-based survey was conducted in 700 villages/wards, selected from the 70 districts of the 21 States of India, categorized into four strata based on the incidence of reported COVID-19 cases. Four hundred adults per district were enrolled from 10 clusters with one adult per household. Serum samples were tested for IgG antibodies using COVID Kavach ELISA kit. All positive serum samples were re-tested using Euroimmun SARS-CoV-2 ELISA. Adjusting for survey design and serial test performance, weighted seroprevalence, number of infections, infection to case ratio (ICR) and infection fatality ratio (IFR) were calculated. Logistic regression was used to determine the factors associated with IgG positivity. RESULTS: Total of 30,283 households were visited and 28,000 individuals were enrolled. Population-weighted seroprevalence after adjusting for test performance was 0.73 per cent [95% confidence interval (CI): 0.34-1.13]. Males, living in urban slums and occupation with high risk of exposure to potentially infected persons were associated with seropositivity. A cumulative 6,468,388 adult infections (95% CI: 3,829,029-11,199,423) were estimated in India by the early May. The overall ICR was between 81.6 (95% CI: 48.3-141.4) and 130.1 (95% CI: 77.0-225.2) with May 11 and May 3, 2020 as plausible reference points for reported cases. The IFR in the surveyed districts from high stratum, where death reporting was more robust, was 11.72 (95% CI: 7.21-19.19) to 15.04 (9.26-24.62) per 10,000 adults, using May 24 and June 1, 2020 as plausible reference points for reported deaths. INTERPRETATION & CONCLUSIONS: Seroprevalence of SARS-CoV-2 was low among the adult population in India around the beginning of May 2020. Further national and local serosurveys are recommended to better inform the public health strategy for containment and mitigation of the epidemic in various parts of the country.

Evaluation of Microscopic observation drug susceptibility (MODS) assay as a rapid, sensitive and inexpensive test for detection of tuberculosis and multidrug resistant tuberculosis.

BACKGROUND: Microscopic observation drug susceptibility (MODS) assay has been suggested as a low cost method for rapid, accurate detection of tuberculosis (TB) and multidrug resistant tuberculosis (MDR-TB). METHODS: A total of 2424 samples collected from 1063 eligible patients of suspected pulmonary or extrapulmonary TB were subjected to MODS assay. Performance of MODS was compared with culture and drug susceptibility testing (DST) by conventional solid Lowenstein-Jensen (LJ) media or liquid Mycobacteria Growth Indicator Tube (MGIT) culture. RESULTS: When compared to reference gold standard of positivity in either solid or liquid reference culture, the MODS assay had sensitivity, specificity, positive predictive value and negative predictive value of 91.3%, 98.2%, 96.0% and 95.9% respectively. MODS took a median time of 10.3 days to culture positivity as compared to 13.8 days using MGIT and 30.5 days using LJ culture. Culture and DST being concurrent in MODS, the median turnaround time for DST was the same as that for culture i.e. 10.3 days. The overall median turn around time for culture positivity and DST using manual MGIT and LJ medium was 23.6 days and 61.2 days respectively. The concordance between MODS culture and the reference susceptibility method was 97.7% for rifampicin, 95.6% for isoniazid, 98.5% for rifampicin and isoniazid. The cost of performing a single MODS assay was INR 200. CONCLUSION: MODS is a rapid and sensitive, yet simple and inexpensive test that may be helpful to enhance diagnostic accuracy, and case detection of TB and MDR-TB in resource constrained settings.

Overlap Syndrome with Rowell's Syndrome, Antiphospholipid Syndrome, Primary Sterility, and Sensorineural Hearing Loss: A Case Report, Brief Review, and Analysis of Cases of Rowell's Syndrome Reported from India and Abroad.

Rowell's syndrome (RS) is recognized since 1963 as a presentation of lupus erythematosus (LE) with erythema multiforme-like lesions and characteristic immunological changes. Antiphospholipid syndrome (APS) encompasses antibodies to phospholipids/phospholipid-binding cofactor proteins and/or circulating lupus anticoagulant with clinical manifestations of thrombosis such as recurrent spontaneous abortions, etc. A 32-year-old female with primary infertility since marriage (7 years) and sequential appearance, for the past 6 months, of various lupus-specific cutaneous lesions, "targetoid" lesions on palms, musculoskeletal, ocular and auditory (sensorineural hearing loss [SNHL]) complaints with positive serological profile for SMD-1, SS-A/Ro, SS-B/La, U1-snRNP, Ku, antiphospholipid and anticardiolipin antibodies, and histopathologically confirmed LE is presented as a case of concurrent overlap syndrome, RS and APS, primary infertility, and SNHL. A brief review of RS including analysis of data of cases reported from India hereto vis-a-vis that of cases worldwide up to 2012 has also been done.

Role of miRNAs in hypoxia-related disorders.

Hypoxia is a complex pathophysiological condition. The physiological and molecular responses to this stress have been extensively studied. However, the management of its ill effects still poses a challenge to clinicians. MicroRNAs (miRNAs) are short non-coding RNA molecules that control post-transcriptional gene expression. The regulatory role of miRNAs in hypoxic environments has been studied in many hypoxia-related disorders, however a comprehensive compilation and analysis of all data and the significance of miRNAs in hypoxia adaption is still lacking. This review summarizes the miRNAs related to various hypoxia-related disorders and highlights the computational approaches to study them. This would help in designing novel strategies toward efficient management of hypoxia-related disorders.

Metabolic syndrome in vitiligo patients among a semi-urban Maharashtrian population: A case control study.

AIM: To assess the prevalence of metabolic syndrome and its correlation with the severity and duration of vitiligo. METHODS: One hundred vitiligo patients and 100 age-and-sex matched controls were included, whose waist circumference and blood pressure were measured; fasting serum cholesterol, triglycerides and glucose levels quantified; disease severity assessed and metabolic syndrome defined by National Cholesterol Education Program (NCEP) criteria. RESULTS: Metabolic syndrome (24%:12%), hypertriglyceridemia (41%:24%), impaired glucose tolerance (25%:16%) [P<0.05] and low HDL (P=0.044) were significantly more prevalent in cases as compared to controls as were the mean values of triglycerides and fasting blood sugar. Increased mean age of vitiligo patients correlated with the presence of metabolic syndrome. CONCLUSION: Metabolic syndrome had significant presence in but remained unaffected by the severity of vitiligo in our study patients.

Rapid identification of Mycobacterium tuberculosis complex in clinical isolates by combining presumptive cord formation and MPT64 Antigen Immunochromatographic Assay.

PURPOSE: Combining the results of presumptive cord formation in smear and MPT64 Antigen Immunochromatographic Assay has been suggested to reduce the false negative and positive rates for identification of Mycobacterium tuberculosis (MTB) complex in liquid culture. This study was done to evaluate the clinical utility of combining the results of the two tests for rapid identification MTB complex in mycobacterial isolates. METHODS: 484 isolates of mycobacteria obtained in MGIT culture were identified using presumptive cord formation in smear and further by MPT64 Antigen ICT assay. Result obtained were analyzed taking PNB inhibition test as the reference standard. RESULTS: Combining the results of the two tests, 464 (95.9%) isolates were correctly identified while discrepant results were obtained in 20 (4.1%) isolates. When the results of the two tests were intersected, the specificity and PPV was 100%, but the sensitivity decreased to 96.4% and the NPV to 68.6%. On the other hand, when the results of the two methods were combined, the sensitivity and NPV was 100%, but the specificity decreased to 88.6% and the PPV to 99.1%. CONCLUSION: Presumptive cord formation and MPT64 antigen ICT assay can be used in combination for identification of MTB complex. When both the test are positive, the culture can be reported to contain MTB complex. If both the tests are negative, the culture should be reported to contain NTM. Only when discrepant results are obtained by the two tests, further evaluation is necessary to ensure an accurate diagnosis.

Nanoscale conductive pattern of the homoepitaxial AlGaN/GaN transistor.

The gallium nitride (GaN)-based buffer/barrier mode of growth and morphology, the transistor electrical response (25-310 °C) and the nanoscale pattern of a homoepitaxial AlGaN/GaN high electron mobility transistor (HEMT) have been investigated at the micro and nanoscale. The low channel sheet resistance and the enhanced heat dissipation allow a highly conductive HEMT transistor (Ids > 1 A mm(-1)) to be defined (0.5 A mm(-1) at 300 °C). The vertical breakdown voltage has been determined to be ∼850 V with the vertical drain-bulk (or gate-bulk) current following the hopping mechanism, with an activation energy of 350 meV. The conductive atomic force microscopy nanoscale current pattern does not unequivocally follow the molecular beam epitaxy AlGaN/GaN morphology but it suggests that the FS-GaN substrate presents a series of preferential conductive spots (conductive patches). Both the estimated patches density and the apparent random distribution appear to correlate with the edge-pit dislocations observed via cathodoluminescence. The sub-surface edge-pit dislocations originating in the FS-GaN substrate result in barrier height inhomogeneity within the HEMT Schottky gate producing a subthreshold current.

Effect of extreme conditions of Antarctica on human leukocyte antigen-G in Indian expeditioners.

BACKGROUND & OBJECTIVES: Immune activation and inflammation play critical roles in the stressful environmental conditions like high altitude, extreme cold, etc. Human leukocyte antigen-G (HLA-G) is a non classical major histocompatiblity complex class I (MHC class- I) protein, upregulated in the context of transplantation, malignancy and inflammation. We hypothesized serum HLA-G as a possible stress biomarker and studied levels of soluble form of HLA-G (sHLA-G) in Indian Antarctic expeditioners. METHODS: sHLA-G ELISA was performed in the serum of summer (n=27) and winter (n=22) Indian Antarctic expeditioners. The summer expeditioners were evaluated at three different time points, i.e. before leaving India, after one month ship borne journey, and after staying one month at Indian research base, Maitri in Antarctica, while winter expeditioners were evaluated at five different time points, i.e. before leaving India, and in the month of March, May, August and November at Antarctica. RESULTS: o0 ne month ship borne journey did not cause any significant change in the sHLA-G level as compared to the baseline level of the summer expeditioners. sHLA-G levels were not changed significantly in the months of March, May, August and November as compared to the baseline level of the winter expeditioners. INTERPRETATION & CONCLUSIONS: Our results indicated that the extreme conditions of Antarctica did not cause any significant change in the sHLA-G level in both summer and winter expeditioners.

Prevalence of risk factors for coronary artery disease in an urban Indian population.

OBJECTIVE: The objective of this study was to assess the prevalence of risk factors for coronary artery disease (CAD) in government employees across India. METHODS: The study population consisted of government employees in different parts of India ({n=10,642 men and n=1966 women; age 20-60 years}) and comprised various ethnic groups living in different environmental conditions. Recruitment was carried out in 20 cities across 14 states, and in one union territory. All selected individuals were subjected to a detailed questionnaire, medical examinations and anthropometric measurements. Blood samples were collected for blood glucose and serum lipid profile estimation, and resting ECG was recorded. Results were analysed using appropriate statistical tools. RESULTS: The study revealed that 4.6% of the study population had a family history of premature CAD. The overall prevalence of diabetes was 16% (5.6% diagnosed during the study and the remaining 10.4% already on medication). Hypertension was present in 21% of subjects. The prevalence of dyslipidemia was significantly high, with 45.6% of study subjects having a high total cholesterol/high density lipoprotein ratio. Overall, 78.6% subjects had two or more risk factors for CAD. CONCLUSIONS: The present study demonstrates a high prevalence of CAD risk factors in the Indian urban population. Therefore, there is an immediate need to initiate measures to raise awareness of these risk factors so that individuals at high risk for future CAD can be managed.

Evaluation of p-nitro benzoic acid (pnb) inhibition test to differentiate Mycobacterium tuberculosis complex from non-tuberculous mycobacteria using microscopic observation of drug susceptibility (MODS) methodology.

BACKGROUND: Microscopically observed drug susceptibility (MODS) assay relies on visualisation of characteristic serpentine cord for identification of Mycobacterium tuberculosis (MTB) complex. Since a few Non-tuberculous mycobacteria (NTM) also form cords or pseudocords, additional tests are required to obviate false positive result. Revised MODS platform by including p-nitro benzoic acid (PNB) in one of the wells is suggested to differentiate MTB from NTM. METHODS: 464 cultures positive by both MODS assay and reference solid LJ/liquid MGIT were included in the study. MODS protocol was modified by addition of a PNB well. Identification of MTB in reference culture methods was done by standard methods. Results obtained were compared with that of modified MODS assay. RESULTS: Overall concordance for species identification between MODS assay and reference solid LJ/liquid MGIT culture on the basis of visual detection of serpentine cords was 94.8% (95% Confidence interval- 92.3%-96.5%). When results of visual detection of serpentine cords were combined with PNB inhibition test, concordance was 100% (95% CI 98.9%-100%). CONCLUSION: Based on results of our study, we recommend modification of MODS assay protocol by adding PNB to one well to differentiate MTB complex from NTM species.

Assessment of clinical profile of the patients treated at ayurvedic health facilities in north India.

Since a very long time, a significant number of patients have been seeking treatment at Complementary and Alternative Medicine health facilities, but the disease burden at these facilities has never been assessed and documented. Present cross-sectional study was carried out at Ayurvedic tertiary care hospital to document and to assess the rationale of disease reporting at Ayurvedic institutions of the northern state of India from January 2011 to October 2011. Almost half of the patients' morbidities were not classified at all into any of the disease categories. The common reported morbidities at study hospital were: Respiratory (10.5%), neuromuscular (9.5%), digestive (9.2%) and circulatory (9.1%) disorders. As the majority of diseases were unclassified, so mainstreaming of the effective disease surveillance would be required to understand the morbidity pattern and successful treatment practices at health facilities.

Heart rate variabilty changes during first week of acclimatization to 3500 m altitude in Indian military personnel.

Acute exposure to hypobaric hypoxia induces the changes in autonomic control of heart rate. Due to emergencies or war like conditions, rapid deployment of Indian military personnel into high altitude frequently occurs. Rapid deployment to high altitude soldiers are at risk of developing high altitude sickness. The present study was conducted to evaluate the acute exposure to high altitude hypobaric hypoxia (3500 m altitude) on the autonomic nervous control of heart rate in Indian military personnel during first week of acclimatization Indices of heart rate variability (viz; R-R interval, total power, low frequency, high frequency, ratio of low to high frequency) and pulse arterial oxygen saturation were measured at sea level and 3500m altitude. Power spectrum of heart rate variability was quantified by low frequency (LF: 0.04-0.15 Hz) and high frequency (HF: 0.15-0.5 Hz) widths. The ratio of LF to HF was also assessed as an index of the sympathovagal balance. Mean R-R interval decreased significantly on day 2 on induction to altitude which tended to increase on day 5. Total power (TP) decreased high altitude and tended to recover within a week. Both HF and LF power showed decrement at 3500m in comparison to sea level. The ratio of LF to HF (LF/HF) at 3500m was significantly higher at 3500m. SpO2 values decreased significantly (P < 0.05) at high altitude on day-2 which increased on day-5. We conclude that autonomic control of the heart rate measured by heart rate variability was altered on acute induction to 3500m which showed a significant decrease in parasympathetic tone and increase in sympathetic tone, then acclimatization seems to be characterized by progressive shift toward a higher parasympathetic tone.

The histone H1 variant accumulates in response to water stress in the drought tolerant genotype of Gossypium herbaceum L.

We have optimized and improved the protocol for extraction of histone proteins from Gossypium herbaceum. Histone proteins were isolated by acid extraction method and fractionation of histone proteins were performed using RP-HPLC (reverse-phase high performance liquid chromatography). Analysis of histones from drought tolerant (Vagad) and drought sensitive genotype (RAHS-14) indicated that the tolerant genotype Vagad encodes a 29 kDa protein. Protein sequencing on MALDI TOF/TOF revealed that the 29 kDA protein shared sequence similarity with another drought-inducible linker histone-H1.S reported in tomato. This H1.S like linker histone was not found in RAHS-14 in our study. We further examined the expression of H1 variant at the transcript and protein levels and found that it was induced specifically in the tolerant genotype Vagad.

Physiological and proteomic responses of cotton (Gossypium herbaceum L.) to drought stress.

Cotton genotype RAHS 187 was analyzed for changes in physiology, biochemistry and proteome due to drought stress. The deleterious effect of drought in cotton plants was mainly targeted towards photosynthesis. The gas-exchange parameters of net photosynthesis (A), stomatal conductance (g(s)) and transpiration (E) showed a decreasing trend as the drought intensity increased. The fluorescence parameters of, effective quantum yield of PSII (Φ(PSII)), and electron transport rates (ETR), also showed a declining trend. As the intensity of drought increased, both H(2)O(2) and MDA levels increased indicating oxidative stress. Anthocyanin levels were increased by more than four folds in the droughted plants. Two-dimensional gel electrophoresis detected more than 550 protein spots. Significantly expressed proteins were analyzed by peptide mass fingerprinting (PMF) using MALDI-TOF-TOF. The number of up-regulated spots was found to be 16 while 6 spots were down-regulated. The reasonable implications in drought response of the identified proteins vis-à-vis physiological changes are discussed. Results provide some additional information that can lead to a better understanding of the molecular basis of drought-sensitivity in cotton plants.

Paenibacillus lentimorbus enhances growth of chickpea (Cicer arietinum L.) in chromium-amended soil.

Chromium (Cr), with its great economic importance in industrial use, is a major metal pollutant of the environment. It affects soil microbial activity and soil fertility, resulting in losses in yield of plants. Paenibacillus lentimorbus B-30488(r) (B-30488(r)) tolerated 200 µg ml(-1) of Cr under in vitro conditions and produced the plant growth promoting substance indole acetic acid in the presence of Cr. Our in vitro study indicates enhancement in B-30488(r) biofilm formation by sodium alginate (SA) and calcium chloride (CaCl(2)) both in absence and presence of supplemented Cr(VI) as compared to unsupplemented control. The plant growth promoting effects caused by the B-30488(r) biofilm in rhizosphere of chickpea under Cr(VI) stress suggests a phytoprotective role of B-30488(r) biofilm. Our study reflects the multifarious role of strain B-30488(r) and presents it as a potent plant growth promoting and bioremediation agent useful in Cr-contaminated rhizosphere soil, whereby the SA and CaCl(2) induced B-30488(r) biofilm on plant root acts as a shield in preventing the direct access of toxic Cr to plant tissues, thus reducing its uptake in plants.