Assessment of HIV-TB co-infection in newly diagnosed HIV positive patients and their correlation with CD4 and viral load

Background: Human Immunodeficiency Virus (HIV) and Tuberculosis (TB) constitute a major burden of infectious diseases in India. TB is the most common opportunistic infection and a leading cause of death among HIV positive patients. This study was conducted to assess the HIV–TB co-infection in newly diagnosed HIV patients and correlate co-infection with CD4 and viral load (VL). Methods: A prospective observational study was carried out from January 2021 to June 2022 at ART center of a tertiary care hospital. Screening for TB was done by GeneXpert and Radiology. These patients were monitored for absolute CD4 count by flow cytometer and VL by Real time PCR. Results: Among 380 newly diagnosed HIV patients screened, 94 (24.70%) had HIV-TB coinfection. Of these, 42 (44.6%) were pulmonary tuberculosis (PTB) and 52 (55.3%) were extrapulmonary tuberculosis (EPTB) of 42 patients with PTB, 31 (73.80%) were microbiologically confirmed by GeneXpert whereas of 52 patients with EPTB, 33 (63.46%) were diagnosed clinically and radio-logically. Of 94 patients, only 55 patients could be followed up further at 6 months. Of 55 patients, 33 (60%) had CD4 count <350 cells/mm3 and 2 (3.6%) had baseline VL≥1000 copies/ml. 46.80% patients completed their anti-tubercular treatment. Conclusions: EPTB was more as compared to PTB. Co-infection was more with low CD4 counts. Hence, CD4 test can be used as a good immunological marker in co-infection. The study highlights the need of periodic screening of newly diagnosed HIV patients for TB and their monitoring for CD4 and VL

Knowledge, stress and adopted coping strategies of parents of children having congenital adrenal hyperplasia: An exploratory survey

Background: Congenital adrenal hyperplasia (CAH) is an inherited disorder of adrenal glands, the most common type being due to a deficiency of the enzyme 21-α-hydroxylase. Girls affected with it are virilized to a variable extent. The taboo associated with ambiguous genitalia in female babies poses an immense societal pressure on parents for keeping the disease a secret. Objective: The aim of the study was to generate the evidence on the knowledge, stress, and coping strategies used by the parents of CAH children. Methodology: In a cross-sectional descriptive survey using mixed methods approach, 30 parents of children with CAH attending the outdoor department of pediatric medicine and surgery in a tertiary care hospital were enrolled. The CAH knowledge questionnaire, parental stress scale (PSS), and COPE inventory were the standardized tools used along with demographic profile sheet to assess the knowledge of parents related to CAH, stress, and coping strategies used by them. Results: Majority of the parents (67%) had poor knowledge (<7) and moderate stress (42-65) scores. Knowledge and stress were negatively correlated (r=−0.39, p=0.035). Coping strategies used by the parents in dealing with stress in moderate amount were mainly problem-focused (active coping [60%] and planning [60%], instrumental social support [53%], suppression of competing activities [50%]), and emotion-focused (positive reinterpretation [60%], emotional social support [67%], acceptance [53%], and religious coping [50%]). Less useful coping strategies such as focus on and venting of emotions, behavioral disengagement, mental disengagement, humor, and substance abuse were not used by the majority parents. Conclusion: Parents of children with CAH had poor knowledge and moderate stress related to the disease condition of their children and were using problem focused and emotion focused coping strategies to reduce their stress

Polar Localization of Virulence-Related Esx-1 Secretion in Mycobacteria

The Esx-1 (type VII) secretion system is critical for virulence of both Mycobacterium tuberculosis and Mycobacterium marinum, and is highly conserved between the two species. Despite its importance, there has been no direct visualization of Esx-1 secretion until now. In M. marinum, we show that secretion of Mh3864, a novel Esx-1 substrate that remains partially cell wall–associated after translocation, occurred in polar regions, indicating that Esx-1 secretion takes place in these regions. Analysis of Esx-1 secretion in infected host cells suggested that Esx-1 activity is similarly localized in vivo. A core component of the Esx-1 apparatus, Mh3870, also localized to bacterial poles, showing a preference for new poles with active cell wall peptidoglycan (PGN) synthesis. This work demonstrates that the Esx-1 secretion machine localizes to, and is active at, the bacterial poles. Thus, virulence-related protein secretion is localized in mycobacteria, suggesting new potential therapeutic targets, which are urgently needed

Targeted Stimuli-Responsive Dextran Conjugates for Doxorubicin Delivery to Hepatocytes

A targeted, stimuli-responsive, polymeric drug delivery vehicle has been developed to help alleviate the severe side-effects caused by narrow therapeutic window drugs. Doxorubicin, a commonly used chemotherapeutic agent has been conjugated to dextran by two different techniques. In the first method, doxorubicin and hepatocyte-targeting galactosamine were attached to dextran through amine bonds. Conjugation efficiency based on the amount loaded of each reactant varied from 1% to 50% for doxorubicin and from 2% to 20% for galactosamine, depending on various synthesis parameters. For the second conjugate, doxorubicin was attached to dextran through an acid-labile hydrazide bond. Fluorescence quenching indicated that all our conjugates can bind to DNA. The degree of binding was improved with increasing polymer molecular weight and substitution of doxorubicin, and also with hydrazide-bonded conjugate. In cell culture experiments, we have found that the uptake of conjugates was much lower than that of free doxorubicin. Lower uptake of conjugates decreased the toxicity of doxorubicin. Also, the uptake of non-galactosylated conjugate was lower than that of the galactosylated conjugate. Microscopy studies indicated that doxorubicin was localized almost exclusively at the nucleus, whereas the amine-bonded conjugates were present throughout the cell. Targeted amine-linked conjugates and hydrazide-bonded conjugates achieved greatly improved cytotoxicity. Following uptake, the doxorubicin was dissociated from the hydrazide conjugate in an endosomal compartment and diffused to the nucleus. The LC₅₀ values of non-targeted amine-linked, targeted amine-linked, and hydrazide-linked doxorubicin were 19.81 μg/mL, 7.33 μg/mL and 4.39 μg/mL, respectively. The amine-linked conjugates were also tested on a multidrug-resistant cell line; the LC₅₀ values of doxorubicin and the non-targeted amine-linked conjugate were 8.60 μg/mL and 36.02 μg/mL, respectively.Singapore-MIT Alliance (SMA

Biomass and carbon stocks in mangrove stands of Kadalundi estuarine wetland, south-west coast of India

Mangroves are keystone ecosystems which provide numerous environmental services. Mangroves assume significance as standing stores of sequestered atmospheric carbon and are therefore, important in the light of climate change mitigation. In this study, we attempted to assess the biomass of mangroves in the Kadalundi wetland, south-west coast of India and evaluated the potential of these mangroves to sequester and store carbon. The C-stocks of above-ground and root biomass were 83.32±11.06 t C ha-1 and 34.96±4.30 t C ha-1 respectively, while the C-stock in sediment was estimated to be 63.87±8.67 t C ha-1. The estimates of mean combined C-stocks in the mangrove biomass and sediment of Kadalundi shows that this estuarine mangrove wetland stored 182.15 t C ha-1, which was equivalent to 668.48 t CO2 ha-1. The mangroves which cover an area of 13.23 ha in the Kadalundi wetland is assumed to have a potential to sequester and store a substantial quantity of 2,409.84 t C which is equivalent to 8,844.11 t CO2. The study underscores the importance of these intertidal forests for climate change mitigation and stresses the importance of protecting the mangroves which provide many other important ecosystem services that benefit communities

Characterizing and Predicting the Future Popularity of Online Videos

ABSTRAC

Correlation between hematological parameters, blood urea level and mortality of COVID-19 patients.

Aim: Present study was aimed to analyze difference of hematological parameters and blood urea level between Recovered and Dead cases of COVID-19. Material & Methods: A hospital based study was undertaken wherein hematological parameters and blood urea level of 65 cases were analyzed. Results: Recovered patients, 16 (42.1%) showed higher levels of neutrophils with corresponding 22 (57.9%) patients showing normal level of lymphocytes, 25 (65.7%) with normal hemoglobin and 35 (92%) with normal blood urea. On other hand, among 27 Died cases, 26 (96.2%) showed higher counts of neutrophils, 1 patient showed normal lymphocytes (3.8%) and 26 (96.2%) with low count of lymphocytes. Conclusion: In majority of cases, recovered patients showed normal range of lymphocytes (20-45%), hemoglobin and blood urea levels, whereas mortality was observed associated with deficiency of lymphocytes (except one patient all belo

Tetrazolylmethyl quinolines: design, docking studies, synthesis, anticancer and antifungal analyses

A new series of 2,5 and 1,5-regioisomers of the tetrazolyl group viz., 3-(5-benzyl/benzylthio-2H-tetrazol-2-yl) methyl-2-chloro-6-substituted quinoline 6h-q and 3-(5-benzyl/benzylthio-1H-tetrazol-1-yl) methyl-2-chloro-6-substituted quinolines 7h-q were synthesized. Docking studies of all these compounds with DNA as target using PDB: 1AU5 and 453D revealed that the compounds 6h and 6i act as covalent cross linker on the DNA helix of the former and intercalate the latter both with higher C score values. Another set of docking studies in the active pocket of dihydrofolate reductase and N-myristoyl transferase as targets to assess antifungal activity revealed that compounds 6k, 6l, 6p and 7q (with bromo and fluro substituents) showcases different binding modes and hydrogen bonding. Further, the compounds were screened for anticancer activity (primary cytotoxicity) against NCI-60 Human tumor cell line at a single high dose (10−5 M) concentration assay. Among the tested compounds, 6h has shown 99.28% of GI against Melanoma (SK-MEL-5) and compound 6i has shown 97.56% of GI against Breast Cancer (T-47D). Further, in vitro antifungal assay against A. fumigatus and C. albicans for these compounds 6h-q and 7h-q revealed potential to moderate activities as compared to the standard

Molecular Basis of Host-Virus Interactions to Explain Relative Transmission and Severity Caused by Omicron and Delta variants of SARS-CoV-2

In India and other affected countries, Omicron variant of SARS-CoV-2 has shown faster transmission but less clinical severities when compared to Delta strain. Present study was aimed to investigate how molecular changes in the spike proteins of Omicron variant has increased its transmission but reduced the disease severity. We report molecular interactions of Spike proteins of Delta and Omicron variants with ACE-2 receptor to explain how change in chemical and physical nature of mutated amino acids of Omicron variant has affected the internalization competence of virus into host cell. The Research Collaboratory Structural Bioinformatics (RCSB) and Protein Data Bank (PDB) were used to construct ACE2-Spike Protein interaction. The binding affinity of both omicron and delta variant spike proteins with human ACE2 receptor was observed. Spike protein of Omicron variants has revealed total number of 93 dissimilarities of amino acids from Delta strain,15 of which are in its Receptor Binding Domain (RBD). Our study showed that RBD of Delta variant contained only one hydrophobic amino acid whereas there were 6 hydrophobic amino acids in the RBD of Omicron variant. We report that increased number of Hydrophobic Amino Acids in RBD of Omicron variant affects its binding with ACE2 receptor to enter into the cell. The failure of internalization of virus has increased concentration of extracellular virions at nasopharyngeal region leading to faster expulsion of infective droplets during coughing or sneezing to increase transmission but has reduced the severity of infection. The reported observations could prove to be of public health and therapeutic significance

Establishment of reference CD4+ T cell values for adult Indian population

<p>Abstract</p> <p>Background</p> <p>CD4+ T lymphocyte counts are the most important indicator of disease progression and success of antiretroviral treatment in HIV infection in resource limited settings. The nationwide reference range of CD4+ T lymphocytes was not available in India. This study was conducted to determine reference values of absolute CD4+ T cell counts and percentages for adult Indian population.</p> <p>Methods</p> <p>A multicentric study was conducted involving eight sites across the country. A total of 1206 (approximately 150 per/centre) healthy participants were enrolled in the study. The ratio of male (N = 645) to female (N = 561) of 1.14:1. The healthy status of the participants was assessed by a pre-decided questionnaire. At all centers the CD4+ T cell count, percentages and absolute CD3+ T cell count and percentages were estimated using a single platform strategy and lyse no wash technique. The data was analyzed using the Statistical Package for the Social Scientist (SPSS), version 15) and Prism software version 5.</p> <p>Results</p> <p>The absolute CD4+ T cell counts and percentages in female participants were significantly higher than the values obtained in male participants indicating the true difference in the CD4+ T cell subsets. The reference range for absolute CD4 count for Indian male population was 381-1565 cells/μL and for female population was 447-1846 cells/μL. The reference range for CD4% was 25-49% for male and 27-54% for female population. The reference values for CD3 counts were 776-2785 cells/μL for Indian male population and 826-2997 cells/μL for female population.</p> <p>Conclusion</p> <p>The study used stringent procedures for controlling the technical variation in the CD4 counts across the sites and thus could establish the robust national reference ranges for CD4 counts and percentages. These ranges will be helpful in staging the disease progression and monitoring antiretroviral therapy in HIV infection in India.</p