Molecular modeling of C1-inhibitor as SARS-CoV-2 target identified from the immune signatures of multiple tissues: An integrated bioinformatics study.

The expeditious transmission of the severe acute respiratory coronavirus 2 (SARS-CoV-2), a strain of COVID-19, crumbled the global economic strength and caused a veritable collapse in health infrastructure. The molecular modeling of the novel coronavirus research sounds promising and equips more evidence about the pragmatic therapeutic options. This article proposes a machine-learning framework for identifying potential COVID-19 transcriptomic signatures. The transcriptomics data contains immune-related genes collected from multiple tissues (blood, nasal, and buccal) with accession number: GSE183071. Extensive bioinformatics work was carried out to identify the potential candidate markers, including differential expression analysis, protein interactions, gene ontology, and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment studies. The overlapping investigation found SERPING1, the gene that encodes a glycosylated plasma protein C1-INH, in all three datasets. Furthermore, the immuno-informatics study was conducted on the C1-INH protein. 5DU3, the protein identifier of C1-INH, was fetched to identify the antigenicity, major histocompatibility (MHC) Class I and II binding epitopes, allergenicity, toxicity, and immunogenicity. The screening of peptides satisfying the vaccine-design criteria based on the metrics mentioned above is performed. The drug-gene interaction study reported that Rhucin is strongly associated with SERPING1. HSIC-Lasso (Hilbert-Schmidt independence criterion-least absolute shrinkage and selection operator), a model-free biomarker selection technique, was employed to identify the genes having a nonlinear relationship with the target class. The gene subset is trained with supervised machine learning models by a leave-one-out cross-validation method. Explainable artificial intelligence techniques perform the model interpretation analysis.

Good survival rate, moderate overall and good respirator quality of life, near normal pulmonary functions, and good return to work despite catastrophic economic costs 6 months following recovery from Acute Respiratory Distress Syndrome.

Introduction: Long-term quality of life, return to work, economic consequences following Acute Respiratory Distress Syndrome (ARDS) are not well described in India. This study was aimed to address the question. Methods: A prospective cohort study of 109 ARDS survivors were followed up for a minimum of 6 months following discharge. Quality of life was assessed using the SF-36 questionnaire. Respiratory quality was assessed using the St Georges Respiratory Questionnaire. Time to return to work was documented. Costs-direct medical, as well as indirect were documented up to 6 months. Results: At 6 months, 6/109 (5.5%) had expired. Low energy/vitality and general heath were noted in the SF-36 scores at 6 months; overall a moderate quality of life. Pulmonary function tests had mostly normalized. Six-min walk distance was 77% of predicted. Respiratory quality of life was good. It took at the median of 111 days to go back Interquartile range (55-193.5) to work with 88% of previously employed going back to work. There were no significant differences in the severity of ARDS and any of these outcomes at 6 months. The average total cost from the societal perspective was ₹ 231,450 (standard deviation 146,430-, 387,300). There was a significant difference between the 3-ARDS severity groups and costs (P < 0.01). There were no independent predictors of return to work. Conclusion: ARDS survivors have low 6-month mortality. Pulmonary physiology and exercise capacity was mostly normal. Overall, quality of life is average was moderate, while respiratory quality of life was good. Return to work was excellent, while cost of care falls under a catastrophic heath expense.

Prospective study to assess the treatment modalities and fever defervescence in patients with scrub typhus from a tertiary care centre in South India.

BACKGROUND AND OBJECTIVES: Fever defervescence in scrub typhus, a zoonotic bacterial infection is used as a surrogate marker of disease resolution. Failure of fever defervescence prompts clinicians to suspect alternate diagnoses and treatment. In this observational study, various treatment regimens were correlated with clinical outcomes. METHODS: All adult patients with a diagnosed scrub typhus were included; various antibiotic regimens used and clinical outcomes were studied. Data was analyzed using SPSS software for windows 16, with a 2-sided P-value of 0.05 or less was considered statistically significant. RESULTS: In 177 hospitalized patients with scrub typhus, combination therapy (doxycycline and azithromycin) was used in 74 subjects with doxycycline and azithromycin used in 46 and 57 subjects, respectively. Incidence of delayed defervescence was seen in 31.6%, Combination therapy being preferred in sicker patients (SOFA score 8.82). Presence of respiratory dysfunction was associated with a delay in fever defervescence [risk ratio 2.50(1.18-5.3)]. Patients receiving doxycycline did better in terms of oxygen requirement and the presence of hypotension. The overall case fatality rate was 5.6%. The severity of illness rather than the choice of antibiotics predicted the outcome in scrub typhus. INTERPRETATION & CONCLUSION: Combination therapy with doxycycline and azithromycin is the most common regimen used. Incidence of delayed defervescence (31.6%) is increasing despite therapy and the involvement of respiratory dysfunction is an independent predictor of delayed fever defervescence.

Outcomes and factors influencing outcomes of critically ill HIV-positive patients in a tertiary care center in South India.

The incidence of (Human immune deficiency) HIV in India has fallen by 58% since the onset of the HIV epidemic. As of 2016 there are 2.1 million people living in India with HIV and only 49% of the adults with HIV are on ART (1). The HIV infected individuals may require intensive care due to various reasons. This study attempts to look at the outcomes of these patients admitted in the intensive care unit and the predictors of these outcomes. AIMS: 1. To assess the outcomes of critically ill HIV infected patients admitted in the medical intensive care unit. 2. Assessment of the factors that are likely to influence the outcome. MATERIALS AND METHODS: it is a retrospective medical review of all the patient records available on our electronic database. The study period was January 2008 - October 2013. RESULTS: in our study cohort the commonest reason for admission into the intensive care unit was sepsis associated with multi organ dysfunction (64%). A low CD 4 count, renal failure acute respiratory distress syndrome, and hypotension and multi organ dysfunction were predictive of a poor outcome in our study. CONCLUSION: The most common cause of admission of PLHIV in ours study cohort was Infections, ART associated side effects and low CD4 counts, presence of multi organ dysfunction, acute respiratory distress syndrome (ARDS), hypotension were associated with adverse outcomes.

Dominance of international high-risk clones in carbapenemase-producing Pseudomonas aeruginosa: Multicentric molecular epidemiology report from India.

BACKGROUND: Pseudomonas aeruginosa is one of the most common opportunistic pathogens that cause severe infections in humans. The burden of carbapenem resistance is particularly high and is on the rise. Very little information is available on the molecular mechanisms and its clonal types of carbapenem-resistant P. aeruginosa seen in Indian hospitals. This study was undertaken to monitor the ß-lactamase profile and to investigate the genetic relatedness of the carbapenemase-producing (CP) P. aeruginosa collected across different hospitals from India. MATERIALS AND METHODS: A total of 507 non-duplicate, carbapenem-resistant P. aeruginosa isolated from various clinical specimens collected during 2014-2017 across seven Indian hospitals were included. Conventional multiplex polymerase chain reaction for the genes encoding beta-lactamases such as extended-spectrum beta-lactamase (ESBL) and carbapenemase were screened. A subset of isolates (n = 133) of CP P. aeruginosa were genotyped by multilocus sequence typing (MLST) scheme. RESULTS: Of the total 507 isolates, 15%, 40% and 20% were positive for genes encoding ESBLs, carbapenemases and ESBLs + carbapenemases, respectively, whilst 25% were negative for the ß-lactamases screened. Amongst the ESBL genes, blaVEB is the most predominant, followed by blaPER and blaTEM, whilst blaVIM and blaNDM were the most predominant carbapenemases seen. However, regional differences were noted in the ß-lactamases profile across the study sites. Genotyping by MLST revealed 54 different sequence types (STs). The most common are ST357, ST235, ST233 and ST244. Six clonal complexes were found (CC357, CC235, CC244, CC1047, CC664 and CC308). About 24% of total STs are of novel types and these were found to emerge from the high-risk clones. CONCLUSION: This is the first large study from India to report the baseline data on the molecular resistance mechanisms and its association with genetic relatedness of CP P. aeruginosa circulating in Indian hospitals. blaVIM- and blaNDM-producing P. aeruginosa is the most prevalent carbapenemase seen in India. Majority of the isolates belongs to the high-risk international clones ST235, ST357 and ST664 which is a concern.

Mycobacterial blood culture as the only means of diagnosis of disseminated tuberculosis in advanced HIV infection.

The diagnosis of disseminated tuberculosis (TB) in advanced HIV infection is often delayed because of difficulty in obtaining suitable specimens for culture. A total of 32 such patients from South India with positive mycobacterial blood cultures were studied over ten years. Almost all (90%) had a febrile illness and the majority (68.7%) had clinical lung involvement, but only 27.3% had positive sputum smears. Liver biopsy yielded a positive diagnosis in only 1/7. Cytopenia was almost universal (96.9%). Bone marrow cultures were, however, positive in 54.8%, of whom one-quarter grew atypical mycobacteria. Mycobacterial blood culture is therefore a useful adjunct test to diagnose TB in advanced HIV.

Lateral medullary syndrome after a scorpion sting.

Scorpion bites are a common problem in Southern parts of India. The sting of Mesobuthus tamulus belonging to the Buthidae family is known for being fatal. The toxidrome of scorpion sting is known for its effect on the cardiovascular system, and there have been rare reports of cerebrovascular accidents as well. We describe a case of lateral medullary syndrome secondary to scorpion sting. As per the knowledge of the authors, this is the first case report of the same.

Paraquat poisoning: Case report of a survivor.

N, N'-dimethyl-4, 4'-bipyridinium dichloride (paraquat) is a widely used synthetic, nonselective contact herbicide. Ingestion of toxic doses of paraquat can be fatal with life-threatening effects on the lungs, gastrointestinal (GI) tract, kidney, liver, heart, and other organs. Till date, there are no specific antidotes and none of the current treatments have proven efficacious. The prognosis is uniformly poor worldwide, including those who treat aggressively with multimodal therapies. Long-term survivors are few, and have GI and pulmonary complications. Hence, prevention needs to be the utmost priority, and on exposure, aggressive decontamination should be initiated. Although it is a very common herbicide, there are very few cases reported from India and awareness among people needs to be widened.

Hansen's disease: An unusual presentation.

Hansen's disease can present with varied and subtle symptoms which can be missed. A middle-aged gentleman presented with swelling of face and hands. Detailed examination and investigations confirmed borderline tuberculoid leprosy with lepra reaction. A high index of suspicion with vigilance can help to make an early diagnosis in this potentially treatable condition.