Disseminated Tuberculosis of the Lungs, Brain, Pleurae, Mediastinal Lymphadenopathy, and Elbow Joint in an Immunocompetent Indian Female: A First-of-Its-Type Case.

Tuberculosis is usually seen in the lungs. However, the involvement of various extrapulmonary sites is due to the spread of the bacteria via blood, lymphatic, or direct inoculation. The present case is a rare presentation of tuberculosis in an Indian female who came with complaints of swelling in her right elbow joint, headache, and cough with expectoration. A diagnostic evaluation resulted in the isolation of Mycobacterium tuberculosis from the sputum samples and elbow joints, which was further supported by an exudative picture on the cerebrospinal fluid examination. The findings were supported by advanced radiometric techniques. She was commenced on an antituberculous treatment per her weight. Disseminated tuberculosis is a challenging diagnosis as there is often a delay in clinical presentation, a lack of awareness about the possibility of multiple sites with tuberculous infection in clinicians, and a time lag in the availability of the culture results.

In-silico immunoinformatic analysis of SARS-CoV-2 virus for the development of putative vaccine construct.

COVID-19 (CoronaVirus disease 2019) is caused by the SARS-CoV-2 virus (severe acute respiratory syndrome corona virus 2). SARS-CoV-2 virus is highly contagious and affects the human respiratory tract resulting in symptoms such as high fever, body ache, cough, dysfunctions of tastebuds and smelling sense of body. The objective of the present study involves immunoinformatic analysis to predict COVID-19 protein for vaccine construct based on the genomic information SARS-CoV-2 virus. At present, as per WHO estimates, around 133 COVID-19 novel vaccines under development. Three amino acid sequences of SARS-CoV-2 were retrieved from the NCBI database for the analysis of vaccine construct. This study involves computational and immunoinformatic methods. The Immunoinformatic tools used in the present study are NetCTL server, IFN epitope server, Toxin PRED, BCPred, CTL + HTL + ADJUVANTS + LINKERS, AlgPredserver, VaxiJenserver, ProtParam to predict vaccine construct. The secondary and tertiary structure prediction is done by PSIPRED, I-TASSER, Galaxy refine, prosA + Ramachandran. Finally, docking of the vaccine constructs and ligand was done with the help of Cluspro 2.0. C-ImmSimm webserver to simulate the potential vaccine construct. The present study demonstrated three potential Vaccine constructs for the SARS-CoV-2 virus, which were docked with TLR8 (Toll-likereceptor8). Interestingly from these, all constructs one having a high potential for the inhibition effect of the SARS-CoV-2virus. Immunological simulation data shows significant elevated amount of memory B cell; also, the high response was seen in TH(Helper) and TC(cytotoxic) cell population from the vaccine construct proposed in the current study. Hence, these constructs are suitable vaccine candidates that might be useful in developing a novel vaccine.

Does conserved domain SOD1 mutation has any role in ALS severity and therapeutic outcome?

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative fatal disease that can affect the neurons of brain and spinal cord. ALS genetics has identified various genes to be associated with disease pathology. Oxidative stress induced bunina and lewy bodies formation can be regulated through the action of SOD1 protein. Hence, in the present study we aim to analyse the structural and functional annotation of various reported SOD1 variants throughout and their putative correlation with the location of mutation and degree of ALS severity by inferring the structural and functional alterations in different SOD1 variants. METHODS: We have retrieved around 69 SNPs of SOD1 gene from Genecards. Structural annotation of SOD1 variants were performed using SWISS Model, I-Mutant 2.0, Dynamut, ConSurf. Similarly, the functional annotation of same variants were done using SIFT, PHP-SNP, PolyPhen2, PROVEAN and RegulomeDB. Ramachandran plot was also obtained for six synonymous SNPs to compare the amino acid distribution of wild-type SOD1 (WT SOD1) protein. Frequency analysis, Chi square analysis, ANOVA and multiple regression analysis were performed to compare the structural and functional components among various groups. RESULTS AND CONCLUSION: Results showed the mutations in conserved domain of SOD1 protein are more deleterious and significantly distort the tertiary structure of protein by altering Gibb's free energy and entropy. Moreover, significant changes in SIFT, PHP-SNP, PolyPhen2, PROVEAN and RegulomeDB scores were also observed in mutations located in conserved domain of SOD1 protein. Multiple regression results were also suggesting the significant alterations in free energy and entropy for conserved domain mutations which were concordant with structural changes of SOD1 protein. Results of the study are suggesting the biological importance of location of mutation(s) which may derive the different disease phenotypes and must be dealt accordingly to provide precise therapy for ALS patients.

Study of nucleolar organizer regions (NORs) in lesions of gallbladder.

Tissue sections from 100 specimens of gallbladder including 40 cases of chronic cholecystitis, 30 cases of epithelial hyperplasia and 30 cases of well, moderately and poorly differentiated adenocarcinoma of gallbladder were studied for argyrophillic nucleolar organizer regions (AgNORs). The arithmetic mean +/- S.D. were calculated for each category. This showed NOR counts of chronic cholecystitis--(1.89+/-0.96), epithelial hyperplasia--(3.99+/-1.03), well differentiated adenocarcinoma (WDCA)--(7.04+/-1.34), moderately differentiated adenocarcinoma (MDCA)--(7.52+/-0.97) and poorly differentiated adenocarcinoma (PDCA)--(8.37+/-1.27). The study revealed increasing number of AgNORS from cases of chronic cholecystitis to epithelial hyperplasia to carcinoma gallbladder, but a considerable overlap in AgNOR counts of individual cases was observed suggesting that though AgNOR count cannot act as a specific diagnostic parameter for diagnosis of early carcinoma & dysplasia in isolated cases, they may prove to be a good adjunct to presently available imaging techniques and cytology.