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The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has adversely affected humankind and caused millions of deaths globally since January 2020. Robust and quick serological tests such as antibody detection assays for SARS-CoV-2 provide relevant information and aid in the process of vaccine development and diagnostics, as well as in sero-epidemiological monitoring of antibody response to the virus. The receptor-binding domain (RBD) of spike and nucleocapsid protein are specific targets for detecting SARS-CoV-2 antibodies. Here, we present the development of a stable spike (S) and nucleocapsid (N) protein-based ELISA antibody detection test "CoroSuchak," with 99% sensitivity, 98% specificity, cost-effective, and detection in a minimum time for serodiagnosis and mass screening of the population for antibodies against SARS-CoV-2. Blood samples were analyzed from 374 SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) positive, 772 negative and asymptomatic, and 874 random groups of subjects. We found that the antibody titer was significantly higher (p 0.0001) in infected and vaccinated group compared to the only vaccinated and only infected group. Using enzyme-linked immunosorbent assay (ELISA), we detected SARS-CoV-2 immunoglobulin G (IgG) antibodies in 118/123 (96%) infected individuals, 570/653 (87%) non-infected but vaccinated individuals, 231/237 (97%) individuals who were both infected and vaccinated, and 499/874 (57%) from randomly selected individuals from the first and second waves of the pandemic. Similarly in the third wave, 14/14 (100%) infected and 16/20 (80%) RT-PCR-negative but symptomatic subjects were detected. Thus, the highly sensitive and specific in-house developed ELISA antibody detection kit "CoroSuchak" is extremely useful to determine the seroprevalence of SARS-CoV-2 antibodies in the coronavirus-exposed population. KEY POINTS: •Indigenous kit using a combination of spike and nucleocapsid proteins and peptide sequences. •High sensitivity and specificity to detect variants. •Highly sensitive for mass screening.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has caused the greatest worldwide pandemic called Coronavirus-2019 (COVID-19) disease. The SARS-CoV-2 virus primarily attacks the respiratory tract, but it also disturbs the gastrointestinal system (GIT). The presence of the angiotensin-converting enzyme-2 (ACE-2) receptor in the intestinal epithelial cells, suggest the transmission of SARS-CoV-2 viruses from lungs to gut through systemic circulation. The virus detected in fecal samples of COVID-19 patients causes several gastrointestinal maladies including vomiting, diarrhea, and pain in abdomen. The gastrointestinal symptoms are associated with alterations in gut microbial composition, an increase in inflammatory cytokines and delayed virus clearance. Several studies demonstrated a decreased abundance of beneficial microbial species and increased opportunistic pathogens in the fecal samples of COVID-19 patients. The gut and lungs, share a bi-directional relationship called the “gut-lung axis” which is modulated by imbalanced gut microbiota. Since the gut microbes are suggested to play a vital role in health and disease by maintaining homeostasis of the immune system, therefore targeting the intestinal dysbiosis with beneficial microbial species, seems plausible to eventually diminish the effects of pulmonary infections and diseases. In this review, we have summarized studies demonstrating the gut-lung axis in association with gut dysbiosis in COVID-19 patients. In addition, the review also highlights the studies showing the potential role of probiotic supplementation in the amelioration of various respiratory infections and diseases. Data demonstrate that the restoration of gut microbial communities by probiotic supplementation can enhance lung capacity to combat respiratory viral infections including SARS-CoV-2.

Over the last twenty months, the attention of the world has been focusing on managing the unprecedented and devastating wave of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) and mitigating its impacts. Recent findings indicated that high levels of pro-inflammatory cytokines are leading cause of poor prognosis in severely ill COVID-19 patients. Presently, the multiple variants and highly contagious nature of virus makes challenge humongous. The shortage and vaccine hesitancy also prompted to develop antiviral therapeutic agents to manage this pandemic. Nanocurcumin has potential antiviral activities and also beneficial in post COVID inflammatory complications. We have developed nanocurcumin based formulation using pyrroloquinoline quinone (PQQ) which protects cardio-pulmonary function and mitochondrial homeostasis in hypobaric hypoxia induced right ventricular hypertrophy in animal model and human ventricular cardiomyocytes. Nanocurcumin based formulation (NCF) with improved bioavailability, has proven several holistic therapeutic effects including myocardial protection, and prevents edema formation, anti-inflammatory and antioxidant properties, maintaining metabolic and mitochondrial homeostasis under hypoxic condition. The post COVID-inflammatory syndrome also reported to cause impaired heart function, lung injuries and increased C-reactive protein level in severely ill patients. Thus, we speculate that NCF could be a new treatment option to manage post COVID-19 inflammatory syndrome.

Abnormal blood coagulation may lead to venous thromboembolism (VTE), a complex multifactorial disease. Hypoxia (oxygen deprivation) is a major factor disturbing the blood hemostasis and predisposing the body towards coagulation and VTE. Pathophysiology of VTE can be attributed to post-transcriptional gene regulation by microRNAs (miRNAs). The present study identified regulatory miRNAs involved in causing blood coagulation under normoxic and hypoxic conditions. Meta-analysis was performed, following PRISMA guidelines, for identifying miRNAs involved in blood coagulation pathway. Studies evaluating miRNAs from circulating blood as potential biomarkers of VTE were selected. A total of 16 studies met selection criteria and 8 having complete statistical information were selected for analysis. Study of blood coagulation mechanism under hypoxic conditions involved in-silico search within highly cited databases to identify miRNAs commonly regulating genes of hypoxia-inducible factor (HIF) family and coagulation pathway. Further bio-informatics approaches were employed to identify potential biomarker candidates. Meta-analysis revealed a panel of 12 miRNAs; two members of miR-27 family, hsa-miR-27a and hsa-miR-27b; two members of miR-320 family, hsa-miR-320a and hsa-miR-320b, hsa-miR-1233, hsa-miR-134, hsa-miR-424-5p, hsa-miR-221, hsa-miR-28-3p, hsa-miR-136-5p, hsa-miR-374-5p and hsa-miR-338-5p involved in blood coagulation under normoxic conditions. Besides these, present in-silico analysis identified a set of 5 miRNAs including hsa-miR-4667-5p, hsa-miR-6815-3, hsa-miR-4433a-3p, hsa-miR-6735-5p and hsa-miR-6777-3p which predominantly regulate genes that facilitate both coagulation and response to hypoxic stress. The present study generated a panel of regulatory miRNAs potentially involved in the process of blood coagulation under both normoxic and hypoxic conditions, which may serve as putative epigenetic biomarkers for coagulation.

Introduction: Coronavirus disease 2019 (COVID-19) is a novel viral disease that spread as a global pandemic in 2020 by infecting millions of people across the world. Its clinical prognosis is dependent on various coagulatory parameters since thrombotic events are frequently associated with infection severity. Methods: A total of 383 COVID-19 patients enrolled in Rajiv Gandhi Super Specialty Hospital, Delhi, India, were included in the present retrospective study. Patients were divided into three categories, severe (n = 141), moderate (n = 138), and mild (n = 104) based on infection severity. Various thrombotic parameters and anticoagulant levels were measured in 70 patients and further analyzed. Results: Coagulopathy is seen in COVID-19 patients (n = 70) with a significant increase in fibrinogen, D-dimer levels, and prothrombin time in patients with severe and moderate disease compared to patients with a mild infection. Approximately, 70% of patients with severe and moderate disease demonstrated fibrinogen levels higher than the standard reference range. 60.41% of patients with severe disease showed significantly higher D-dimer levels. Thrombotic parameters were notably elevated in the nonsurvivors group compared to COVID-19 survivors. Nearly, 91% of patients with severe infection had anticoagulant protein S levels below the reference range. Conclusion: COVID-19 infection severely impacts the blood coagulation cascade, which might lead to the manifestation of severe symptoms and increased mortality in patients.

Human microbial alterations are associated with environmental stress, nutrition, genetic, and triggering de-novo variations. Nevertheless, the human gut microbiome at extreme altitude (> 5800 m) remains unexplored. We aimed to demonstrate the microbial predominance in individuals with the same ethnicity and dietary pattern at extreme altitude with unique challenges like cold, hypoxia, radiation, etc. Different analysis pipelines were used for fecal whole genome sequencing at 210 m, 3500 m, 4420 m and 5805 m, and 16S rRNA V3-V4 regions amplification sequencing of 19 individuals belonging to the same ethnicity and dietary pattern for the presence of taxonomy and functional potential and confirming the prediction up to the strain level within the same cohort. Principal component analysis revealed distinct microbiome changes at different altitudes, with varied and higher Bacteroides and Prevotella ratio. There was a predominance of genus Prevotella at altitudes 4420 m and 5805 m than at 210 m and 3500 m. The appearance of species Prevotella copri strain 61,740 increased significantly at extreme altitude, whereas co-occurrence of other bacterial strains had a different pattern than Prevotella. The extensive strain-level analysis indicated alteration in the metabolic pathways. This study under the stressful and hypoxic environment of extreme altitudes, associated microbial variation with altered metabolic pathways, reveals the influence of extreme environment on human gut microbiota with the predominance of Prevotella.

Mucosal immunity of Indian Antarctic personnel was analysed during the 34th Indian Scientific Expedition to Antarctica (ISEA) by ship voyage. Serum and salivary IgA, IgA1 and IgA2 levels along with salivary cortisol and TGF-β were quantified by enzyme-linked immunosorbent assay. Samples were collected at three different time points (T1, T2 and T3) during the expedition. Serum and salivary IgA, IgA1 and IgA2 concentrations incrementally increased towards the end of the expedition as compared to the beginning of the expedition. Salivary IgA and TGF-β levels were significantly altered during the expedition. Levels of IgA1 (P = 0.0007) and IgA2 (P = 0.0135) increased significantly at T3 as compared to T1. Additionally, significant changes in serum IgA were observed, with peak levels at T3 (P = 0.0015) and T2 (P < 0.001). However, the level of serum IgA2 was also significantly altered at T3 (P < 0.05) and T2 (P = 0.0006) in comparison with T1. The exact cause of the changes in serum and salivary IgA, IgA1, IgA2 and TGF-β levels during the summer expedition are unknown; however, the changes are evident in mucosal immunity.

Background: Chikungunya virus (CHIKV) is an arthropod-borne RNA virus which induces host Endoplasmic Reticulum (ER) stress by accumulating unfolded or misfolded proteins. ER stress activates the unfolded protein response (UPR) pathway to enable proper protein folding and maintain cellular homeostasis. There is no approved drug or vaccine available for CHIKV treatment, therefore, a pharmacological countermeasure is warranted for preventing CHIKV infection. Objective: With a view to find a treatment modality for chikungunya infection, “andrographolide”, a plant-derived diterpenoid with reported antiviral, anti-inflammatory and immunomodulatory effects, was used to investigate its role in chikungunya induced unfolded protein stress and apoptosis. Methods: Cells and supernatant collected on andrographolide and VER-155008, a GRP78 inhibitor, treatment in CHIKV infected and mock-infected THP-1 cells were tested for differential expression of UPR pathway proteins including GRP78, PERK, EIF-2α, IRE-1α, XBP-1 and ATF6. Furthermore, the inflammasome and apoptosis pathway proteins, i.e., caspase-1, caspase-3 and PARP, were tested by immunoblotting, and cytokines, i.e., IL-1β, IL-6 and IFN-γ were tested by ELISA. Results: Andrographolide treatment in CHIKV infected THP-1 cells significantly reduced IRE1α and downstream spliced XBP1 protein expression. Furthermore, CHIKV induced apoptosis and viral protein expression were also reduced on andrographolide treatment. A comparative analysis of andrographolide versus VER-155008, confirmed that andrographolide surpasses the effects of VER-155008 in suppressing the CHIKV induced ER stress. Conclusion: The study, therefore, confirms that andrographolide is a potential remedy for chikungunya infection and suppresses CHIKV induced ER stress and apoptosis.

High altitude pulmonary edema (HAPE) is a life threatening non-cardiogenic pulmonary edema that occurs in an otherwise healthy individuals travelling to altitude above 2500 m. Earlier studies have reported association of mutations in nuclear (nDNA) and mitochondrial DNA (mtDNA) with HAPE susceptibility. However, the molecular mechanisms involved in the pathobiology of HAPE have not been fully understood. The present study investigates the genetic predisposition to HAPE by analyzing the mtDNA mutations in HAPE susceptibles (

Alterations in the gut immune axis under hypobaric hypoxia (HH) exposure may be a consequence of microbial dysbiosis. The mechanism of induction of gut inflammation by alterations in gut bacterial and viral populations has not been discovered meticulously. Here we used whole-genome and 16S rRNA sequencing to characterize the taxonomic and functional shifts in the faecal microbiome after HH exposure. Ten faecal samples from unexposed and HH exposed (3 days, 7 days and 14 days) Sprague–Dawley rats were analyzed. 16S rRNA sequencing was conducted on Illumina MiSeq platform using universal primers and analysed using QIIME (Greengenes database). WGS sequencing was done on Illumina HiSEQ 2500 platform and analysed using MOCAT2 (eggNOG database). HH exhibited an overarching effect on taxonomic and functional gene composition. A significant change in α-diversity at phylum level and β-diversity at phylum and genus level were observed between control and HH exposed groups. Significant (p

BackgroundPathophysiology of venous thrombo-embolism (VTE) depends upon several acquired, inherited and environmental risk factors, including high altitude (HA) exposure. The present study aims to gain insights into pathophysiological mechanism(s) of high altitude induced VTE (HA-VTE) by studying global methylation signatures.MethodologyBlood samples were collected from Indian Army volunteers divided into four study groups; sea level control (SLC), sea level VTE patients (SL-VTE), high altitude control (HAC) and high altitude VTE patients (HA-VTE). Methylation patterns were studied using whole genome bisulfate sequencing. Differentially methylated genes and pathways were identified by comparing percentage methylation.ResultsHighest DM was observed in SL-VTE (1162 gene) compared to SLC where in hyper methylation was predominant (62.9%) compared to hypo methylation (37.05%). A reverse trend was observed in HA-VTE, where hypo methylation (61.69%) was predominant over hyper methylation (38.30%) in a total of 296 DM genes. Differential hypomethylation of genes involved in cell adhesion/platelet activity (CADM1, PTPRK, PDGFA) and immune response (CXCL12, IL4, IRF4, NLRP1) was observed in HA-VTE whereas genes encoding transcription factors (GSC, RPSKA1), trans membrane receptor (NOTCH2) and growth factor (TGFB2) were hypermethylated in comparison to SL-VTE. Methylation pattern of HA-VTE compared to HAC showed hypomethylation in genes involved in oxidative phosphorylation (CPOX), immune response and stress response (NDRG1), while those involved in signaling mechanisms (KALRN), neurotransmitter release (TMPRSS2) and transcription factor (ELF1) were hyper-methylated.ConclusionsOur study for the first time reveals genome wide methylation pattern in HA-VTE group where in differential hypo methylation in cell adhesion and inflammation genes was observed.

Coronavirus disease 2019 (COVID-19) continuously affecting the lives of millions of people. The virus is spread through the respiratory route to an uninfected person, causing mild-to-moderate respiratory disease-like symptoms that sometimes progress to severe form and can be fatal. When the host is infected with the virus, both innate and adaptive immunity comes into play. The effector T cells act as the master player of adaptive immune response in eradicating the virus from the system. But during cancer and chronic viral infections, the fate of an effector T cell is altered, and the T cell may enters a state of exhaustion, which is marked by loss of effector function, depleted proliferative capacity and cytotoxic effect accomplished by an increased expression of numerous inhibitory receptors such as programmed cell death protein 1 (PD-1), lymphocyte-activation protein 3 (LAG-3), and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) on their surface. Various other transcriptional and epigenetic changes take place inside the T cell when it enters into an exhausted state. Latest studies point toward the induction of an abnormal immune response such as lymphopenia, cytokine storm, and T cell exhaustion during SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection. This review sheds light on the dysfunctional state of T cells during chronic viral infection and COVID-19. Understanding the cause and the effect of T cell exhaustion observed during COVID-19 may help resolve new therapeutic potentials for treating chronic infections and other diseases.

Wildlife strikes (mainly birds, but also includes bats and other mammals on the ground) with aircraft isa serious economic and safety concern in the aviation industry. The solution to the problem can be evolved byidentifying the species involved in the incidents/ accidents. In the Indian context, such an attempt was started in1980. In the recent past, the Indian Air Force adopted the DNA Bar-coding technology to identify the species involved. The extent of the problems faced by the country and involvement of different species in various time blocks has been compared with the objective of analyzing changes over different periods to gauge the changes and assess the future requirements. The data indicates that over the years, the number of strikes has increased manifold in the civil aviation sector. The number of species involved in strikes has almost doubled. The serious strikes due to Vultures have nearly disappeared and their place has been mainly taken over by Black Kites. In the recent past, Black Kites are the cause of the highest damages and also have the highest probability of causing damages (61.17%) when struck. Adoption of DNA Barcoding technology has helped to identify the species in incidents where minimal bird remnants were found. Although the number of accidents has decreased, the economical losses continue to rise due to the high cost of modern aircraft.

Background Wintering is associated with distress to humans who work in the isolated and confined environment of Antarctica and yoga has been proved helpful for coping with stress. Therefore, a study was conducted on 14 winter expedition members of Indian Scientific Antarctic Expedition (2016) to find out the effects of yoga on stress-related markers. Methods Participants were divided into yoga, and control (non-yoga) groups. The yoga group practiced yoga for 10 months (from January to October 2016) daily in the morning for an hour. The Resilience test questionnaire was administrated at baseline and endpoint of the study. Blood samples were collected during the study at different intervals for the estimation of 8-hydroxydeoxyguanosine (8-OHdG), brain-derived neurotrophic factor (BDNF), serotonin and cortisol using ELISA. Results A trend of improvement was observed in the resilience test score in the yoga group. From January to October, 8-OHdG serum values in the yoga group declined by 55.9% from 1010.0 ± 67.8 pg/mL to 445.6 ± 60.5 pg/mL (Mean ± SD); in the control group, the decline was 49.9% from 1060.4 ± 54.6 pg/mL to 531.1 ± 81.8 pg/mL. In serotonin serum levels in the yoga group, there was a 3.1% increase from 6.4 ± 1.6 ng/mL to 6.6 ± 0.4 ng/mL while no increase was noticed in the control group. Cortisol values in the yoga group decreased by 19.9% from 321.0 ± 189.6 ng/mL to 257.1 ± 133.8 ng/mL; in the control group it increased by 2.8% from 241.2 ± 51.8 ng/mL to 247.8 ± 90.9 ng/mL. Conclusions It could be concluded from the present study that following 10 months yoga practice may be useful for better resilience and management of stress-related blood markers for the polar sojourners.

Background Extreme environments are inherently stressful and are characterized by a variety of physical and psychosocial stressors, including, but not limited to, isolation, confinement, social tensions, minimal possibility of medical evacuation, boredom, monotony, and danger. Previous research studies recommend adaptation to the environment to maintain optimal function and remain healthy. Different interventions have been tried in the past for effective management of stress. Yoga practices have been shown to be beneficial for coping with stress and enhance quality of life, sleep and immune status. Objective The current article describes preparation of a Yoga module for better management of stressors in extreme environmental condition of Antarctica. Materials and methods A Yoga module was designed based on the traditional and contemporary yoga literature as well as published studies. The Yoga module was sent for validation to forty experts of which thirty responded. Results Experts (n = 30) gave their opinion on the usefulness of the yoga module. In total 29 out of 30 practices were retained. The average content validity ratio and intra class correlation of the entire module was 0.89 & 0.78 respectively. Conclusion A specific yoga module for coping and facilitating adaptation in Antarctica was designed and validated. This module was used in the 35th Indian Scientific expedition to Antarctica, and experiments are underway to understand the efficacy and utility of Yoga on psychological stress, sleep, serum biomarkers and gene expression. Further outcomes shall provide the efficacy and utility of this module in Antarctic environments.

Outbreak of COVID-19 pandemic in December 2019 affected millions of people globally. After substantial research, there is no specific and reliable biomarker available till date. Present study was designed to identify specific biomarkers to predict COVID-19 severity and tool for formulating treatment. A small cohort of subjects (n=43) were enrolled and categorized in four study groups; Dead (n=16), Severe (n=10) and Moderate (n=7) patients and healthy controls (n=10). Small RNA sequencing was done on Illumina platform after isolation of microRNA from peripheral blood. Differential expression (DE) of miRNA (patients groups compared to control) revealed 118 down-regulated and 103 up-regulated known miRNAs with fold change (FC) expression ≥2 folds and p≤0.05. DE miRNAs were then subjected to functional enrichment and network analysis. Bioinformatic analysis resulted in 31 miRNAs (24 Down-regulated; 7 up-regulated) significantly associated with COVID-19 having AUC>0.8 obtained from ROC curve. Seventeen out of 31 DE miRNAs have been linked to COVID-19 in previous studies. Three miRNAs, hsa-miR-147b-5p and hsa-miR-107 (down-regulated) and hsa-miR-1299 (up-regulated) showed significant unique DE in Dead patients. Another set of 4 miRNAs, hsa-miR-224-5p (down-regulated) and hsa-miR-4659b-3p, hsa-miR-495-3p and hsa-miR-335-3p were differentially up-regulated uniquely in Severe patients. Members of three miRNA families, hsa-miR-20, hsa-miR-32 and hsa-miR-548 were significantly down-regulated in all patients group in comparison to healthy controls. Thus a distinct miRNA expression profile was observed in Dead, Severe and Moderate COVID-19 patients. Present study suggests a panel of miRNAs which identified in COVID-19 patients and could be utilized as potential diagnostic biomarkers for predicting COVID-19 severity.

Ship voyage to Antarctica is a stressful journey for expedition members. The response of human gut microbiota to ship voyage and a feasible approach to maintain gut health, is still unexplored. The present findings describe a 24-day long longitudinal study involving 19 members from 38th Indian Antarctic Expedition, to investigate the impact of ship voyage and effect of probiotic intervention on gut microbiota. Fecal samples collected on day 0 as baseline and at the end of ship voyage (day 24), were analyzed using whole genome shotgun sequencing. Probiotic intervention reduced the sea sickness by 10% compared to 44% in placebo group. The gut microbiome in placebo group members on day 0 and day 24, indicated significant alteration compared to a marginal change in the microbial composition in probiotic group. Functional analysis revealed significant alterations in carbohydrate and amino acid metabolism. Carbohydrate-active enzymes analysis represented functional genes involved in glycoside hydrolases, glycosyltransferases and carbohydrate binding modules, for maintaining gut microbiome homeostasis. Suggesting thereby the possible mechanism of probiotic in stabilizing and restoring gut microflora during stressful ship journey. The present study is first of its kind, providing a feasible approach for protecting gut health during Antarctic expedition involving ship voyage.

High mobility group box 1 (HMGB1) is an endogenous alarmin that drives the pathogenesis of neurodegenerative disorders including cognitive decline. Therefore, HMGB1 is thought to be a common biomarker as well as promising therapeutic target for neuroinflammation associated with neurocognitive disorders. Here, for the first time, we have unmasked the potential inhibitory effect of a novel receptor of HMGB1-CXCL12 complex; atypical chemokine receptor 3 (ACKR3/CXCR7) on HMGB1 induced glial phenotype switching, neuroinflammation, and subsequent memory loss. Upregulation of CXCR7 inhibits HMGB1-CXCL12 complex induced peripheral immune cells infiltration to CNS by regulating blood-brain barrier (BBB) integrity in HMGB1 induced dementia model of mice. Whereas, gene knockdown study by RNA interference (non-invasive intranasal delivery to animal model) shows CXCR7 ablation aggravates inflammatory responses in hippocampus region and immune cell infiltration to CNS tissue by breached BBB. This study also indicates the important role of CXCR7 molecule in maintaining CNS homeostasis by balancing M1/M2 microglia, A1/A2 astrocytes, long term potentiation/long term depression markers which ultimately ameliorates HMGB1 induced neurodegeneration, synaptic depression and memory loss (assessed by both radial arm maze and Morris water maze) in male mice model of dementia. Overall, the study summarizes several significant protective functions afforded by CXCR7 against HMGB1 induced disbalance in neuroimmunological axis, neurodegeneration and memory loss and thereby provides a new paradigm for strategic development of novel therapeutics against neurodegenerative diseases with dementia as a common symptom.

Venous thrombosis (VT) is the third major cause of mortality in the world after heart attack and stroke. Its two major clinical manifestations are deep vein thrombosis (DVT) and pulmonary embolism (PE) which are serious medical conditions but often remain under-diagnosed. Although rate of occurrence of venous thrombosis in men is slightly higher, a number of studies have pointed out that woman poses higher risk of venous thromboembolism (VTE) compared to men at various stages of life. Risk of VTE increases in women’s life particularly with use of oral contraceptives, during pregnancy and with exogenous administration of hormones like in post-menopausal hormone therapy. Various reports show that these factors increase risk of DVT and PE by several folds. DVT is considered as an important cause of maternal death in western countries. It is often asymptomatic and its signs and symptoms are similar to those of normal pregnancy. The hormonal changes at various stages of life and less physical activity increase the risk of VTE by blood flow stasis. It is extremely important for women to know the stages of life when they are prone to develop VTE, about its prevention and treatment. Detailed studies on differences in clinical manifestations of VTE between men and women are lacking. This review focusses on assessing the increased risk of VTE and its prognosis in women based on available literature.

Polar T3 syndrome is a common ailment for polar sojourners. It is characterised by abnormal fluctuations of thyroid hormones during extended polar winter. A randomised controlled study was conducted on 14 winter expedition members of Indian Scientific Expedition (2016) to Antarctica by introducing customised yoga module. Blood samples were collected during January to October, 2016 at different intervals for the estimation of total thyroxine (TT4), total triiodothyronine (TT3), thyroid stimulating hormone and noradrenaline (NA) by ELISA. In October yoga group showed significant (p = 0.04) higher TT3 values (2.1 ng/ml ± 0.9; mean ± SD) as compared to the control (0.7 ng/ml ± 0.6). In October a significant difference (p=0.0085) was observed between yoga and control group for NA values (47.0 pg/ml ± 22.0 and 107 pg/ml ± 46.0). Thyroid response of control group at the end of the study revealed presence of polar T3 syndrome in control group. Results indicate that regular yoga practice helped mitigating polar T3 syndrome

Traditional antibiotic susceptibility testing methods take several days to confirm and start disease treatment. The lack of new antibiotics or drugs warrants a need for optimization of current diagnostic tools for immediate antibiotic susceptibility testing. We present a rapid screening method to evaluate the response of bacteria to antibiotics based upon the electrochemical measurement of live bacterial cell metabolic activity using an electroactive redox dye, resazurin. A thin film of Pt deposited over a glass substrate using the direct current sputtering technique was used as a working bio-electrode for electrochemical readouts. X-ray diffraction and scanning electron microscopy was carried out to characterize the Pt thin film. We tested the efficacy of the method using two different strains, Klebsiella pneumoniae (ATCC-700603) and Escherichia coli (ATCC-25922), against ampicillin, kanamycin and tetracycline. The dye, on incubation with viable bacteria, undergoes reduction and lowers the corresponding peak current value. However, in the presence of an effective antibacterial agent, reduction did not occur due to bacterial cell death and absence of a reducing environment. The electrochemical changes in peak current values were monitored using the differential pulse voltammetry technique and interpretation of the results obtained was based upon changes in peak current values. Our results depict a new methodology where a concentration of 104 cells/mL cells can be detected in less than 4 h. The results were also compared with the conventional disc diffusion method for susceptibility testing which has a bacterial incubation time of 18–24 h. The method can potentially be used for monitoring the susceptibility of bacterial strains towards existing antibacterial agents in an easy, rapid, reliable and inexpensive manner without any pre-cultivation of bacteria.

Based on 12 male volunteers we investigated through blood samples at four distinct time-points if a sojourn of 90 days in the Antarctic environment induces or impels significant alterations in platelet activation and inflammatory cytokines. The levels of coagulation signatures in terms of platelet activation molecules, clotting time, clot rate, key inflammatory cytokines and coagulation-associated inflammatory markers were measured. Significant enhancement in the expression of platelet activation molecules and cytokines was observed with shortened clotting time, most prominent during the ship's approach to the continent. In conclusion, exposure to the Antarctic environment correlated with hyper activation of platelets and inflammatory cytokines, indicative of the pro-coagulative state.

High altitude-induced gastrointestinal (GI) problems are potentially life-threatening. GI tract bleeding and inflammation are the major problems induced by hypobaric hypoxia (HH). In this study, effects of acute exposure to HH up to 14 days at 7620 m on GI immune function have been studied. To fulfill these objectives, Sprague-Dawley (SD) rats were divided into five groups namely Control and HH exposed (1, 3, 7, and 14 days). All groups except control were exposed to 7620 m of HH in an animal decompression chamber for the respective time intervals. Different degrees of intestinal mucosal damage in terms of increased mucosal permeability and disruption of intestinal villi were observed for different time intervals. HH exposure also upregulated secretory immunoglobulin A (sIgA) and proinflammatory cytokines in GI lavage along with proinflammatory markers such as toll-like receptor 4 (TLR4) and inducible nitric oxide synthase (iNOS). HH exposure of rats for 7 days significantly increased interleukin-17 (IL-17) and natural killer (NK) cell and dendritic cell populations compared with unexposed control rats. However, the number of naive T cells was significantly decreased in Peyer's patches. Our results connect HH to GI immune axis and highlight Th17 cells and proinflammatory molecules as potential therapeutic targets to counteract HH-induced GI dysfunction.

The rise of antibiotic resistance is an emerging problem of the millennium. Clinical microbiology plays an important role in combating the problem by facilitating diagnostics and therapeutics thus managing infection in patients. Diagnostic failures are a major limiting factor during bacterial infection that causes inappropriate use of antibiotics, delay in start up of treatment and decrease in the survival rate during septic conditions. Thus rapid and reliable detection is highly relevant during such bacterial infections and also at the time of disease outbreak as many such pathogens can be used as biothreat agents or bioweapons affecting human health and posing risk to national security. This review highlights the importance of various methods for fast pathogen detection and antimicrobial susceptibility determination. These methods have the potential to provide very precise and rapid ways for bacterial screening and identifying the correct antibiotics to cure infection

Exposure to heat stress (HS) elicits systemic and cellular response in experimental animals and humans. The current study was undertaken to determine the effect of HS on liver microstructure and function in rats. A heat simulation chamber with ambient temperature (Ta) 45 ± 0.5 °C and relative humidity (RH) 30 ± 5 per cent was used to expose animals to HS. Rats were categorised as moderately heat stressed (MHS, Tc = 40 °C) and severely heat stressed (SHS, Tc = 42 °C) group. We observed that with rise in core temperature (Tc) alanine aminotransferase(ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels were increased but glucose level was decreased in both plasma and liver tissue. Significantly elevated levels of reactive oxygen species (ROS) and nitric oxide (NO) were detected in liver of MHS and SHS animals. Additionally, glutathione disulfide and glutathione (GSSG and GSH) ratio was found to be increased with rise in Tc which suggested saturation in antioxidant capacity of tissue. Furthermore, levels of heat shock proteins (HSPs) and caspases were upregulated upon HS. Results of histological examination indicated extensive loss of cells in liver parenchyma leading to disorganisation of lobular structure. Thus, biochemical and histological studies in experimental animals demonstrates that HS may severely altered structural and biochemical functions of liver.

Heat stress impairs physiology and overall functionality of the body at tissue and organ level in animals. Liver being a vital organ performs more than hundreds regulatory functions of the body. Present study investigates the modulation of molecular pathways that are responsible for liver damage triggered by heat stress. Male Sprague dawley rats were exposed to heat stress (45 °C) in heat simulation chamber till core temperature reaches 40 °C and 42 °C in 25 and 42 min respectively. For in-depth evaluation of liver functions during severe heat stress, hepatic transcriptome and proteome were analysed by microarray and two dimensional gel electrophoresis respectively. Results revealed major alterations in redox status, inflammation, mitochondrial dysfunction and proteostasis related pathways. Data of molecular pathway analysis demonstrate that nuclear factor erythroid 2-related factor 2 (NRF-2) mediated oxidative stress response and macrophage migration inhibitory factor (MIF) regulated inflammatory pathways were upregulated in severe heat stressed liver. Expression levels of downstream molecules of above pathways such as heat shock protein 90AB 1, peroxiredoxin 5, Jun N-terminal kinases 1/2, heme-oxygenase 1, apolipoprotein 1 and interleukin 10 were examined and result suggested the upregulation of these genes modulates the NRF-2 and MIF regulated pathways in heat stressed liver. Irregularity in molecular signalling networks lead to mitochondrial dysfunction indicated by upregulation of ATP synthase β and peroxiredoxin 1 along with decreased levels of glucose-6-phosphate dehydrogenase and enhanced activity of cytochrome c in liver mitochondria. Thus, current study demonstrated heat induced alterations in key liver functions were regulated by NRF-2 and MIF pathways. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12079-022-00668-0.

Khanna, Kunjan, Kamla Prasad Mishra, Sudipta Chanda, Lilly Ganju, Shashi Bala Singh, and Bhuvnesh Kumar. Effect of synbiotics on amelioration of intestinal inflammation under hypobaric hypoxia. Hig...

BackgroundGiven 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 conclusionA 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.

Aim Environmental heat stress alters physiological and biochemical functions which leads to multiorgan dysfunction including severe hepatic injury in animals. We hypothesize that heat preconditioning can be potential intervention in combating heat illnesses. Main methods Sprague Dawley rats were exposed to moderate heat stress, severe heat stress and heat preconditioning in heat simulation chamber. Mean arterial pressure, heart rate, skin and core temperature were monitored in pre and post heat exposed animals. After stress exposure, blood for hemodynamic and liver tissue for liver function tests, oxidative stress, inflammatory variables and structural studies were collected from rats. Hepatic mitochondria were isolated to study the key structural alterations and functional changes by transmission electron microscopy. Key findings The effect of heat precondition shows improvement in time to attain the core temperature, weight loss, blood pressure and heart rate in rats. Results exhibited decreased levels of liver function tests, elevated levels of free radicals and inflammatory cytokines in heat exposed liver as compared with heat preconditioned animals. Expression levels of mitochondrial heat shock protein 60, superoxide dismutase 1 and uncoupling protein 1 along with activity of electron transport chain complexes I-V were examined and found to be increased in heat preconditioned as compared to heat stressed animals. Morphological studies of liver parenchyma demonstrated reduction in structural deterioration of hepatic lobules and restoration of mitochondrial structural integrity in heat preconditioned rats. Significance Present study suggests that heat preconditioning intervention plays a crucial role in protection against heat induced hepatic injury in animals.

Human microbial alterations are associated with environmental stress, nutritional, genetic and triggering de-novo variations. Nevertheless, human gut microbiome at extreme altitude (>5800 m) remains unexplored. We aimed to demonstrate the microbial predominance in individuals with same ethnicity and dietary pattern at extreme altitude with unique challenges like cold, hypoxia, radiation etc. Different analysis pipelines were used for fecal whole genome sequencing at 210m, 3500m, 4420m and 5805m, and 16s rRNA V3-V4 regions amplification sequencing of 19 individuals belonging to the same ethnicity and dietary pattern, for presence of taxonomy & functional potential and confirming the prediction upto the strain level within the same cohort. Principal component analysis, revealed distinct microbiome changes at different altitudes, with varied and higher Bacteroides and Prevotella ratio. There was predominance of genus Prevotella at altitudes 4420m & 5805m than at 210m & 3500m. Appearance of species Prevotella copri strain 61740 was increasing significantly at extreme altitudes, whereas co-occurrence of other bacterial strains had different pattern than Prevotella. The extensive strain level analysis indicated alteration in the metabolic pathways. This study under stressful and hypoxic environment of extreme altitudes, associated microbial variation with altered metabolic pathways, reveals influence of extreme environment on human gut microbiota with predominance of Prevotella.

In view of 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, diagnostic markers etc have created a new race to curb the disease. To uncover nSARS-CoV-2-related important biological features and understanding the molecular basis of this disease, network biology and miRNA-gene regulatory motif-based approach is used. 11 antiviral human-microRNAs (miRNAs) which can potentially target SARS-CoV-2 genes were collated; their direct miRNA interactors were identified and a comprehensive nSARS-CoV-2 responsive miRNA:Transcription Factor (TF):gene coregulatory network was built. 1385 miRNA:TF:gene tripartite, Feed-Forward Loops (FFLs) were identified from the network. The network topology was mapped into the biological space and the overrepresented pathways were identified. Four regulatory circuits: hsa-mir-9-5p-EP300-PLCB4, hsa-mir-324-3p-MYC-HLA-F, hsa-mir-1827-E2F1-CTSV and hsa-mir-1277-5p-SP1-CANX are identified. These miRNA-gene regulatory circuits are found to regulate signalling pathways like virus endocytosis, viral replication, inflammatory response, pulmonary vascularization, cell cycle control, virus spike protein stabilization, antigen presentation, etc. Some novel computational evidences for understanding nSARS-CoV-2 molecular mechanisms controlled by these regulatory circuits is put forth. The novel associations of miRNAs and genes identified with this infection are open for experimental validation. Further, these regulatory circuits also suggest potential correlations/similarity in the molecular mechanisms during nSARS-CoV-2 infection and pulmonary diseases and thromboembolic disorders. A detailed molecular snapshot of TGF-β signalling pathway as the common mechanism that could play an important role in controlling common pathophysiology i.e. systemic inflammation, increased pulmonary pressure, ground glass opacities, D-dimer overexpression is also put forth.

The number of hospitalization of COVID-19 patients with one or more comorbid diseases is highly alarming. Despite the lack of large clinical data and incomplete understanding of virus pathology, identification of the COVID-19 associated diseases with clinical precision are highly limited. In this regard, our text mining of 6238 PubMed abstracts (as on 23 April 2020) successfully identified broad spectrum of COVID-19 comorbid diseases/disorders (54), and their prevalence on the basis of the number of occurrence of disease terms in the abstracts. The disease ontology based semantic similarity network analysis revealed the six highly comorbid diseases of COVID-19 namely Viral Pneumonia, Pulmonary Fibrosis, Pulmonary Edema, Acute Respiratory Distress Syndrome (ARDS), Chronic Obstructive Pulmonary Disease (COPD) and Asthma. The disease gene bipartite network revealed 15 genes that were strongly associated with several viral pathways including the corona viruses may involve in the manifestation (mild to critical) of COVID-19. Our tripartite network- based repurposing of the approved drugs in the world market revealed six promising drugs namely resveratrol, dexamethasone, acetyl cysteine, Tretinoin, simvastatin and aspirin to treat comorbid symptoms of COVID-19 patients. Our animal studies in rats and literatures strongly supported that resveratrol is the most promising drug to possibly reduce several comorbid symptoms associated with COVID-19 including the severe hypoxemia induced vascular leakage. Overall, the anti-viral properties of resveratrol against corona virus could be readily exploited to effectively control the viral load at early stage of COVID-19 infection through nasal administration.