Comparison of local versus intramuscular steroid injection in patients with carpal tunnel syndrome: A prospective open label randomized clinical trial.

AIM: This study compared the efficacy and safety of local corticosteroid injection (LCI) vs intramuscular (IM) corticosteroid injection in mild to moderate carpal tunnel syndrome (CTS). METHODS: This is an open labeled, randomized controlled trial conducted during December 2021 to August 2023. Eighty-six patients with CTS were randomized in 1:1 ratio to receive either single 40 mg methylprednisolone (MP) injection at the wrist (LCI arm), or single 40 mg MP intramuscular injection (IM arm) in the deltoid. Primary outcome was absolute Symptom Severity Scale (SSS) at 3 months. Secondary outcomes were SSS score at 1-month, Functional Status Scale (FSS) score at 1 and 3 months, and recurrence at 3 months and injection site pain assessed on visual analog (VAS) scale. RESULTS: Median age was 45 (range 22 - 80) years, and 86 % were females. Baseline characteristics were comparable between groups. Mean SSS score at 3 months was similar in two arms (1.72 ± 0.71 vs 2.0 ± 0.93) with mean difference (MD) -0.03 (-0.31 to 0.25, p = 0.83) after adjusting for baseline SSS scores. LCI, however, resulted in significantly better SSS (1.48 ± 0.51 vs 1.88 ± 0.69, adjusted p = 0.04), and FSS scores (1.57 ± 0.44 vs 1.80 ± 0.66, adjusted p = 0.03) at 1 month compared to IM arm. Response rate (67.4 % vs 55.8 %; p = 0.30) and recurrence rate (17.1 % vs 22.6 %, p = 0.74) at 3 months were similar. Injection site pain was severe in LCI arm[median 5 (range 3 - 8) vs median 3 (range 2 - 6)]. CONCLUSIONS: In patients with mild to moderate CTS, LCI resulted in better improvement in the BCTQ scores at 1 month compared to IM steroid. However, 3-month's outcome was similar. Intramuscular steroid injection was better tolerated.

Narratives of childhood sexual abuse: healing through music in Ian McEwan's On Chesil Beach.

Narratives of survivors or by survivors offer useful and compelling insights into the experiences of abuse and its consequent effect on health. Reading such narratives can help a physician or clinician to understand the complexities of abuse. Furthermore, the critical study of narratives can open multiple therapeutic options for survivors of abuse to cater both their mental health and medical problems. In this article, we deal with the genre of childhood sexual abuse survivor's narrative and its clinical application adding to the discourse of medical humanities and then critically examine one such narrative (On Chesil Beach by Ian McEwan) in particular and explore the therapeutics of music in abused victim's clinical care.

Fibrin and Fibrinolytic Enzyme Cascade in Thrombosis: Unravelling the Role.

Blood clot formation in blood vessels (thrombosis) is a major cause of life-threatening cardiovascular diseases. These clots are formed by αA-, ßB-, and ϒ-peptide chains of fibrinogen joined together by isopeptide bonds with the help of blood coagulation factor XIIIa. These clot structures are altered by various factors such as thrombin, platelets, transglutaminase, DNA, histones, and red blood cells. Various factors are used to dissolve the blood clot, such as anticoagulant agents, antiplatelets drugs, fibrinolytic enzymes, and surgical operations. Fibrinolytic enzymes are produced by microorganisms (bacteria, fungi, etc.): streptokinase of Streptococcus hemolyticus, nattokinase of Bacillus subtilis YF 38, bafibrinase of Bacillus sp. AS-S20-I, longolytin of Arthrobotrys longa, versiase of Aspergillus versicolor ZLH-1, etc. They act as a thrombolytic agent by either enhancing the production of plasminogen activators (tissue or urokinase types), which convert inactive plasminogen to active plasmin, or acting as plasmin-like proteins themselves, forming fibrin degradation products which cause normal blood flow again in blood vessels. Fibrinolytic enzymes may be classified in two groups, as serine proteases and metalloproteases, based on their catalytic properties, consisting of a catalytic triad responsible for their fibrinolytic activity having different physiochemical properties (such as molecular weight, pH, and temperature). The analysis of fibrinolysis helps to detect hyperfibrinolysis (menorrhagia, renal failure, etc.) and hypofibrinolysis (diabetes, obesity, etc.) with the help of various fibrinolytic assays such as a fibrin plate assay, fibrin microplate assay, the viscoelastic method, etc. These fibrinolytic activities serve as a key aspect in the recognition of numerous cardiovascular diseases and can be easily produced on a large scale with a short generation time by microbes and are less expensive.

Structural-functional analysis and molecular characterization of arsenate reductase from Enterobacter cloacae RSC3 for arsenic biotransformation.

Enterobacter cloacae RSC3 isolated from an industrial pesticide site transformed arsenate into arsenite. The arsenate is transported by membrane-bound phosphate transporter and transformed to arsenite by arsenate reductase (arsC). E. cloacae RSC3 produced an arsenate reductase enzyme with a maximum activity of 354 U after 72 h of incubation. Arsenate reductase was found to be active and stable at a wide range of temperatures (20 and 45 °C) and pH (5-10), with maximum activity at 35 °C and pH 7.0. The arsenate reductase protein was further characterised molecularly using different bioinformatics tools. The 3D structure of ArsC protein was predicted by homology modelling and validated by the Ramachandran plot with 91.9% residues in the most favoured region. ArsC protein of E. cloacae RSC3 revealed structural homology with ArsC from PDB ID: 1S3C. The gene ontology results also showed that the ArsC protein had a molecular functionality of the arsenate reductase (glutaredoxin) activity and the biological function of cellular response to DNA damage stimulus. Molecular docking analysis of 3D structures using AutoDock vina-1.5.7 server predicted four ligand binding active site residues at Gln70, Asp68, Leu68, and Leu63. Strong ArsC-arsenate ion interaction was observed with binding energy -1.03 kcal/mol, indicating significant arsenate reductase activity and specificity of ArsC protein. On the basis of molecular dynamics simulation analysis, the RMSD and RMSF values revealed the stability of ArsC protein from E. cloacae RSC3. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03730-9.

Green synthesis of zinc oxide nanoparticles using lychee peel and its application in anti-bacterial properties and CR dye removal from wastewater.

In nanoscience and nanobiotechnology, using plant extracts in synthesizing metal nanoparticles (NPs) has recently come to light as an exciting opportunity with several benefits over traditional physicochemical methods. In the present work, zinc oxide (ZnO) based nanoparticles (NPs) were synthesized by green chemistry route using lychee peel extract to capture hazardous congo red dye from wastewater and illustrate their antimicrobial behavior. The X-Ray Diffraction (XRD) spectra confirm the wurtzite crystal structure, and Fourier Transform Infrared (FTIR) spectra confirm the functional group in ZnO, which is suitable for dye adsorption. It was found that the NPs were spherical and had a size of <10 nm. The synthesized ZnO NPs could effectively remove >98% of CR dye from wastewater within 120 min of contact time at a wide pH range from 2 to 10. The primary mechanism involved in removing dye was the electrostatic interaction between ZnO adsorbent and CR dye. The antimicrobial performance of synthesized ZnO NPs was found to show 34% inhibition against Bacillus subtilis (ATCC 6538), 52% against Escherichia coli (ATCC 11103), 58% against Pseudomonas aeruginosa (ATCC 25668) and 32% against Staphylococcus aureus (ATCC 25923) using well diffusion assay. ZnO demonstrates a suitable anti-bacterial property over both gram-positive and gram-negative pathogenic bacteria. Overall, the green synthesized method for developing ZnO NPs shows promising and significant anti-bacterial performance and is a highly potential adsorbent for removing CR dye from wastewater.

Microbial lipopeptides: Properties, mechanics and engineering for novel lipopeptides.

Microorganisms produce active surface agents called lipopeptides (LPs) which are amphiphilic in nature. They are cyclic or linear compounds and are predominantly isolated from Bacillus and Pseudomonas species. LPs show antimicrobial activity towards various plant pathogens and act by inhibiting the growth of these organisms. Several mechanisms are exhibited by LPs, such as cell membrane disruption, biofilm production, induced systematic resistance, improving plant growth, inhibition of spores, etc., making them suitable as biocontrol agents and highly advantageous for industrial utilization. The biosynthesis of lipopeptides involves large multimodular enzymes referred to as non-ribosomal peptide synthases. These enzymes unveil a broad range of engineering approaches through which lipopeptides can be overproduced and new LPs can be generated asserting high efficacy. Such approaches involve several synthetic biology systems and metabolic engineering techniques such as promotor engineering, enhanced precursor availability, condensation domain engineering, and adenylation domain engineering. Finally, this review provides an update of the applications of lipopeptides in various fields.

Comparison of Human Epididymis Protein 4, Cancer Antigen 125, and Ultrasound Prediction Model in Differentiating Benign from Malignant Adnexal Masses.

Background: This study aimed to compare the diagnostic performance of carcinogenic antigen (CA) 125, (HE)-4 (Human epididymis protein 4), and ultrasound (International Ovarian Tumor Analysis [IOTA]) Simple Rules individually and to derive a composite score in the differentiating ovarian cancer from benign ovarian mass. Subjects and Methods: Consecutive patients (n = 100) with pelvic mass admitted during February 2018-August 2019 were included prospectively. Patients with either known case of epithelial ovarian cancer (EOC) or metastatic EOC were excluded. The primary outcome was to assess the sensitivity and specificity of CA-125, HE-4, and IOTA Simple Rules in predicting benign from malignant mass independently, while secondary outcome was derivation of a new model incorporating these variables using multivariate logistic regression analysis to predict benign from malignant lesions. Receiver operator curve (ROC) was drawn to redefine the best-performing cutoff values and difference between area under the ROC (AUROC) were compared by DeLong's method. Results: Out of 100 cases of adnexal mass selected, the sensitivity and specificity of CA-125 were 73.8% and 77.6%, HE-4 were 90.5% and 87.9%, and IOTA Simple Rules were 92.9% and 81.0%. CA-125, HE-4, and IOTA Simple Rules were independently associated with the likelihood of malignancy/borderline (P < 0.001). The area under the curve for the "composite score" (AUC = 0.93) was the highest and was significantly better than that of CA-125 (AUC = 0.786) (P = 0.004 using DeLong's test) and comparable with HE-4 (AUROC = 0.90; P = 0.128 using DeLong's Test). Conclusion: The sensitivity and specificity of HE-4 and IOTA Simple Rules for predicting malignant ovarian tumor was better than those of CA-125. The diagnostic performance of "composite score" was comparable to those of either HE-4 or IOTA Simple Rules and significantly better than CA-125.

Dose-Effect Relationship of Motor Nerve Inexcitability on Outcome in Guillain-Barré Syndrome: A Prospective Cohort Study.

Objective: One or more inexcitable motor (IM) nerves are common during electrodiagnostic (EDx) study in Guillain-Barré syndrome (GBS). This study assessed the dose-effect relationship of IM nerves on outcome in patients with acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor and/or sensory axonal neuropathy (AMAN and AMSAN). Materials and Methods: Eighty-eight GBS patients admitted during May 2018-June 2023 underwent detailed clinical evaluation and EDx study. Admission and follow-up disability were assessed on a 0-10 Clinical Grading Scale (CGS). Outcome was recovery at 6 months, defined as good (CGS <3) and poor (CGS ≥3). Binary multivariate logistic regression with backward elimination was used to calculate independent predictors of outcome. Results: Proportion of patients with complete recovery decreased significantly with increasing numbers of IM nerves (P < 0.01). Seventy-six patients were followed for 6 months. Among patients with IM nerves (n = 28), complete recovery was similar between AIDP and axonal GBS (70% vs. 50%, respectively; P = 0.40). However, in patients with recordable compound muscle action potentials (CMAPs) in all the motor nerves (n = 26), axonal GBS had significantly poor recovery compared to AIDP (75% vs. 9.1%; P = 0.01). Among patients receiving intravenous immunoglobulin (IVIg; n = 42), poor recovery was seen in 53.6% with IM nerves compared to 35.7% without (P = 0.28), while it was 37.5% versus 5.6% (P = 0.04), respectively, in those who did not receive IVIg (n = 34). However, only admission disability (odds ratio [OR] 0.88, 95% confidence interval [CI] 0.81-0.97; P = 0.007) was found to be an independent predictor of outcome. Conclusion: Although increasing numbers of IM nerves were associated with poor outcome on univariate analysis, they did not predict 6 months' outcome independently. Outcome did not differ between axonal GBS and AIDP among those with IM nerves. IVIg improved outcome in patients with IM nerves.

Predictors of Posterior Reversible Encephalopathy Syndrome (PRES) in Women With Pre-eclampsia/Eclampsia: A Retrospective Analysis.

CONTEXT:  Posterior reversible encephalopathy syndrome (PRES) is a clinical-radiological entity characterized by acute neurological symptoms with reversible subcortical vasogenic brain edema. One of the most common risk factors is pre-eclampsia/eclampsia. AIMS:  This study aimed to compare the clinical and radiological characteristics of PRES with those without PRES in patients with pre-eclampsia/eclampsia and attempts to find independent predictors of PRES. METHODS AND MATERIALS:  This was a single-center, retrospective study. Fifty-three female patients admitted to the Department of Obstetrics & Gynaecology, AIIMS Rishikesh between 2018 and 2021 with severe pre-eclampsia/eclampsia were included. Brain imaging was done to confirm the diagnosis of PRES. Baseline characteristics between patients whose imaging was suggestive and not suggestive of PRES were compared. RESULTS:  Fifty-three patients with pre-eclampsia/eclampsia were included in the analysis. The median age and period of gestation of the study population were 28 (range 19-37) years and 36.6 (range 24.2-41.5) weeks respectively. Twelve patients (22.6%) had eclampsia, and 41 (87.4%) had pre-eclampsia of which 28 (52.8%) had severe pre-eclampsia. Twelve patients were diagnosed with PRES. Patients with PRES were significantly younger with a median age of 23 [range 20-30 vs 29 (range 19-37; p = 0.005) years], and more likely to be primiparous (91.7% vs 36.6%; p < 0.001) compared to those without PRES. PRES was significantly more common in patients with eclampsia. Of 12 patients with eclampsia, nine (75%) had evidence of PRES. The maternal and fetal outcome, however, was similar in both groups. Patients with PRES were more likely to have poor sensorium compared to those without PRES (83.3% vs 5.3%; p < 0.01). Eclampsia was found in the independent predictor of PRES (odds ratio, OR 20.9; 95% confidence interval, CI 3.0-147.0, p = 0.02). CONCLUSIONS:  In this study, patients with PRES were younger and significantly more likely to be primiparous and have eclampsia compared to those without PRES. Headache followed by seizures and altered sensorium were the most common clinical manifestations and subcortical white matter hyperintensities involving fronto-parieto-occipital lobes were the most common radiological finding. Eclampsia emerged as an independent risk factor for PRES.

An Insight into Efflux-Mediated Arsenic Resistance and Biotransformation Potential of Enterobacter Cloacae RSC3 from Arsenic Polluted Area.

Indiscriminate discharge of heavy metals/metalloids from different sources into the sustainable agro-ecosystem is a major global concern for food security and human health. Arsenic (As), categorized as group one human carcinogen is a quintessential toxic metalloid that alters the microbial compositions and functions, induce physiological and metabolic changes in plants and contaminate surface/ground water. The management of arsenic toxicity, therefore, becomes imminent. Acknowledging the arsenic threat, the study was aimed at identifying arsenic resistant bacteria and evaluating its arsenic removal/detoxification potential. Of the total 118 bacterial isolates recovered from arsenic rich environment, the bacterial strain RSC3 demonstrating highest As tolerance was identified as Enterobacter cloacae by 16S rRNA gene sequence analysis. Enterobacter cloacae tolerated high concentration (6000 ppm) of As and exhibited 0.55 h-1 of specific growth rate as calculated from growth kinetics data. Strain RSC3 also displayed varying level of resistance to other heavy metals and many antibacterial drugs in plate bioassay. The bacterial strain RSC3 possessed gene (arsC) which causes transformation of arsenate to arsenite. The arsenate uptake and efflux of the bacterial cells was revealed by high throughput techniques such as AAS, SEM/TEM and EDX. The simultaneous As reducing ability, and multi metal/multi-antibiotics resistance potentials of E. cloacae provides a promising option in the microbes based remediation of As contaminated environments.

Deciphering the genetic and functional diversity of cultivable bacteria from chasmophytic pigweed (Chenopodium album) from Tsomoriri, Ladakh, India.

Chasmophytes are a group of diverse plants growing on cracks and crevices of rocks. They survive under nutrient and water-limited conditions. Microorganisms associated with chasmophytes may play a critical role in their survival. In the present study, 263 bacterial isolates were obtained from chasmophytic wild Chenopodium collected from Tsomoriri, Ladakh. Members of Enterobacter, Pseudomonas, Pantoea, and Alcaligenes comprised ~ 90% of the Gram-negative bacteria, while among Gram-positive, Bacillus, Solibacillus, Fictibacillus, Microbacterium, and Micrococcus were most abundant. When evaluated for various plant growth-promoting traits, 36 bacteria could solubilize insoluble phosphate, 10 bacteria could release potassium from silicate minerals, and 25 bacteria could solubilize ZnO, while 124 bacteria produced siderophores. ACC deaminase activity was present in 31 isolates, while 46 bacteria could produce IAA (10.40-232.0 µg/mL). Furthermore, more than 64% of the isolates could grow at 50 °C, while ~ 60% could grow at 4 °C. Similarly, ~ 50% isolates were able to grow with > 1.7 M NaCl and ~ 70% could grow under high osmolarity (~ 67 mOsmol/L). The ability of these microorganisms to grow under such a wide range of temperature, salinity, and osmolarity offers adaptive advantage to colonize plants surviving under harsh environmental conditions. A large number (30-49%) of these isolates could produce acids from various sugars and sugar alcohols which is crucial to release mineral nutrients trapped in the rocks. The results indicated that genetically and functionally diverse microflora associated with wild Chenopodium might be helping these plants to effectively mine nutrients and water under extreme conditions. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03278-0.

Chicken Feather Waste Valorization Into Nutritive Protein Hydrolysate: Role of Novel Thermostable Keratinase From Bacillus pacificus RSA27.

Microbial keratinases exhibit a momentous role in converting keratin biowastes into exceedingly valuable protein supplements. This study reports a novel, highly stable keratinase from Bacillus pacificus RSA27 for the production of pure peptides rich in essential amino acids from chicken feathers. Purified keratinase showed a specific activity of 38.73 U/mg, 2.58-fold purification, and molecular weight of 36 kDa. Kinetic studies using a chicken feather as substrate report K m and V max values of 5.69 mg/ml and 142.40 µg/ml/min, respectively, suggesting significant enzyme-substrate affinity/biocatalysis. Identification and in silico structural-functional analysis of keratinase discovered the presence of distinct amino acid residues and their positions. Besides, keratinase possesses a high-affinity calcium-binding site (Asp128, Leu162, Asn164, Ile166, and Val168) and a catalytic triad of Asp119, His151, and Ser308, known attributes of serine protease (subtilisin family). Furthermore, a scale-up to 5 L fermenter revealed complete feather hydrolysis (94.5%) within 24 h with high activity (789 U/ml) and total amino acid of 153.97 µmol/ml. Finally, cytotoxicity evaluation of protein hydrolysate resulted in negligible cytotoxic effects (1.02%) on the mammalian hepatoblastoma cell line, signifying its potential biotechnological applications.

Internal student migration in India: Impact of the COVID-19 crisis.

The education sector in India was among the most affected sectors during the COVID-19 pandemic. While considerable attention has been paid to informal workers' return or reverse migration to their home communities, not much has been reported about the challenges faced by migrant students. Using a mixed-method approach, the current study presents an overview of internal student migration in India prior to the COVID-19 pandemic using data from the 2001 and 2011 Census of India and the 2007-2008 National Sample Survey Organization, and discusses challenges faced by selected migrant learners during the COVID-19 pandemic based on primary research. Based on the census data, nearly 3.3 million migrants in India move for study reasons with 2.9 million migrating within the state (with the duration of residence less than five years) from their last residence within India. The pattern of female student migration suggests an increasingly localized interdistrict migration. Findings from the qualitative data indicate that during the pandemic, students had compromised learning and placement experience, inadequate digital resources and pressure to repay loans. Student migrants experienced varying degrees of the impact of the COVID-19 pandemic based on their destination and migration stream.

Pseudomonas mediated nutritional and growth promotional activities for sustainable food security.

Numerous microbial communities show synergistic and antagonistic interactions among themselves, resulting in benefit and harm to either or both the associated members. The association holds accountability for nutrients recycling and energy drift, resulting in the availability of macronutrients unavailable and insoluble forms of rhizospheric nutrients, crucial for vital processes in plants, e.g., act as co-factors of various phyto-enzyme and redox mediators. Plant growth promoting rhizobacteria are known to enhance plant growth by increasing these macronutrients availability during their plant root colonization. In comparison to any other genera, Pseudomonas is the most favored bioinoculant due to its significant properties in both plant growth and phytopathogen control during its synergistic association with the host plant. These properties include siderophore production, phosphate solubilization, nitrogen fixation, phenazines, antibiotics, and induced systemic resistance carried out by various Pseudomonas species like Pseudomonas fluorescens, Pseudomonas putida, and Pseudomonas syringae. The association of Pseudomonas with crop plants procures several secretory and electron-based feedback mechanisms in order to regulate the plant growth and phytopathogen control activities through the secretion of several phytohormones (auxins, gibberellins, Indole-3-acetic acid), secondary metabolites (flavonoids) and enzymes (aminocyclopropane-1-carboxylate, phenylalanine ammonia-lyase). Ecologically significant applications of Pseudomonas in biocontrol and bioaugmentation are crucial for maintaining food security.

Microbial Fibrinolytic Enzymes as Anti-Thrombotics: Production, Characterisation and Prodigious Biopharmaceutical Applications.

Cardiac disorders such as acute myocardial infarction, embolism and stroke are primarily attributed to excessive fibrin accumulation in the blood vessels, usually consequential in thrombosis. Numerous methodologies including the use of anti-coagulants, anti-platelet drugs, surgical operations and fibrinolytic enzymes are employed for the dissolution of fibrin clots and hence ameliorate thrombosis. Microbial fibrinolytic enzymes have attracted much more attention in the management of cardiovascular disorders than typical anti-thrombotic strategies because of the undesirable after-effects and high expense of the latter. Fibrinolytic enzymes such as plasminogen activators and plasmin-like proteins hydrolyse thrombi with high efficacy with no significant after-effects and can be cost effectively produced on a large scale with a short generation time. However, the hunt for novel fibrinolytic enzymes necessitates complex purification stages, physiochemical and structural-functional attributes, which provide an insight into their mechanism of action. Besides, strain improvement and molecular technologies such as cloning, overexpression and the construction of genetically modified strains for the enhanced production of fibrinolytic enzymes significantly improve their thrombolytic potential. In addition, the unconventional applicability of some fibrinolytic enzymes paves their way for protein hydrolysis in addition to fibrin/thrombi, blood pressure regulation, anti-microbials, detergent additives for blood stain removal, preventing dental caries, anti-inflammatory and mucolytic expectorant agents. Therefore, this review article encompasses the production, biochemical/structure-function properties, thrombolytic potential and other surplus applications of microbial fibrinolytic enzymes.

Association of IFN-gamma and IL-10 gene variants with the risk of extrapulmonary tuberculosis.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) is a chronic infectious disease. Interferon-gamma (IFN-γ) is an important cytokine imparting resistance to mycobacterial diseases. It is believed that IFN-γ and Interleukin-10 (IL-10) play divergent roles in the host immune system against MTB infection. IL-10 is an important inhibitory cytokine and helps balancing the inflammatory and immune responses. IL-10 is involved in down regulation of Th1 cytokines, MHC class II antigen and co-stimulatory molecular expression on macrophages, while IFN-γ results in macrophage activation allowing them to exert the microbicidal role. The objectives were to find out the association of IL-10 (-1082 A/G) and IFN-γ (+874 A/T) single nucleotide polymorphisms (SNPs) with extrapulmonary tuberculosis in ethnic Kashmiri population. A total of 100 extrapulmonary tuberculosis cases and 102 healthy controls were analyzed for IL-10 (-1082 A/G) and IFN- γ (+874 A/T) SNPs using Allele-Specific PCR. We found a significant association of IFN-γ + 874 'TT' genotype with extrapulmonary tuberculosis (p = 0.006) and in case of IL-10 (-1082 A/G) we found a significant association with extrapulmonary tuberculosis under recessive model (GG vs GA + AA) (p = 0.03) in Kashmiri population. IL-10 (-1082 A/G) and IFN-γ (+874 A/T) have a significant association with extrapulmonary tuberculosis in ethnic Kashmiri population.

Computational-approach understanding the structure-function prophecy of Fibrinolytic Protease RFEA1 from Bacillus cereus RSA1.

Microbial fibrinolytic proteases are therapeutic enzymes responsible to ameliorate thrombosis, a fatal cardiac-disorder which effectuates due to excessive fibrin accumulation in blood vessels. Inadequacies such as low fibrin specificity, lethal after-effects and short life-span of available fibrinolytic enzymes stimulates an intensive hunt for novel, efficient and safe substitutes. Therefore, we herewith suggest a novel and potent fibrinolytic enzyme RFEA1 from Bacillus cereus RSA1 (MK288105). Although, attributes such as in-vitro purification, characterization and thrombolytic potential of RFEA1 were successfully accomplished in our previous study. However, it is known that structure-function traits and mode of action significantly aid to commercialization of an enzyme. Also, predicting structural model of a protein from its amino acid sequence is challenging in computational biology owing to intricacy of energy functions and inspection of vast conformational space. Our present study thus reports In-silico structural-functional analysis of RFEA1. Sequence based modelling approaches such as-Iterative threading ASSEmbly Refinement (I-TASSER), SWISS-MODEL, RaptorX and Protein Homology/analogY Recognition Engine V 2.0 (Phyre2) were employed to model three-dimensional structure of RFEA1 and the modelled RFEA1 was validated by structural analysis and verification server (SAVES v6.0). The modelled crystal structure revealed the presence of high affinity Ca1 binding site, associated with hydrogen bonds at Asp147, Leu181, Ile185 and Val187residues. RFEA1 is structurally analogous to Subtilisin E from Bacillus subtilis 168. Molecular docking analysis using PATCH DOCK and FIRE DOCK servers was performed to understand the interaction of RFEA1 with substrate fibrin. Strong RFEA1-fibrin interaction was observed with high binding affinity (-21.36 kcal/mol), indicating significant fibrinolytic activity and specificity of enzyme RFEA1. Overall, the computational research suggests that RFEA1 is a subtilisin-like serine endopeptidase with proteolytic potential, involved in thrombus hydrolysis.

Role of genetic variants of Vitamin D receptor, Toll-like receptor 2 and Toll-like receptor 4 in extrapulmonary tuberculosis.

BACKGROUND: Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (MTB). Vitamin D deficiency and vitamin D receptor (VDR) gene abnormalities confer susceptibility to tuberculosis. Toll-like receptors (TLRs), such as TLR-2, are also important mediators of inflammatory response against Mycobacterium tuberculosis. We evaluated VDR, TLR-2 and TLR-4 gene polymorphisms in patients with extrapulmonary tuberculosis (EPTB). OBJECTIVES: To find out a possible association of Vitamin D receptor (VDR) (rs731236), TLR-2 (196-174 Ins > Del) and TLR-4 (Thr399Ile) gene polymorphisms with extrapulmonary tuberculosis in ethnic Kashmiri population. METHODS: A total of 100 extrapulmunary tuberculosis cases and 102 healthy controls were analyzed for Vitamin D receptor (VDR) (rs731236), TLR-2 (196-174 ins > del) and TLR-4 (Thr399Ile) gene polymorphisms using PCR-RFLP and Allele-Specific PCR methods. RESULTS: We found increased frequency of TLR-4 Thr/Ile heterozygous genotype in cases as compared with healthy controls (22% vs 5.8%). Thus acting as a risk factor for extrapulmonary tuberculosis, as was elucidated from statistical analysis [OR, 4.5; 95% CI (1.74-11.68); P < 0.001]. In case of TLR-2 (196-174 ins > del) we observed significant differences in the homozygous variant (Del/Del) genotype of cases and controls (28% in cases & 2.94% in controls). Thus, TLR-2 (Del/Del) genotype acts as a strong risk factor for extrapulmonary tuberculosis predisposition [OR, 12.2; 95% CI (3.5-42.69); P < 0.001]. We did not find any significant differences in the genotypic distribution of (VDR) (rs731236) T > C SNP between cases and controls (P > 0.05). CONCLUSION: TLR-4 (Thr/Ile) and TLR-2 (Del/Del) act as significant risk factors for extrapulmonary tuberculosis predisposition in ethnic Kashmiri population.

Concrete Crack Restoration Using Bacterially Induced Calcium Metabolism.

Concrete structures are prone to develop cracks and cause devastation. Repair and renovation are not enough to ensure complete eradication of crack development. The entire process is costly and laborious. The microbiologically induced calcium carbonated precipitation can be effective in restoring the cracks. The calcium-based nutrients along with specific bacterial strain have been used in the present investigation. The pellets of calcium as per Fourier transform infrared spectroscopy and energy-dispersive X-ray spectroscopy are deposited in the cracks of the concrete over a period of 7 days of incubation. The presence of bacteria in the calcium precipitates as demonstrated by scanning electron microscope provides adequate strength and adhering quality to the pellets. The effective filling of cracks is confirmed with the help ultrasonic pulse velocity test also. Since, elephantine heritage and high sky buildings have high maintenance costs, the use of present technique will cut down the cost and duration of restoration. SUPPLEMENTARY INFORMATION: The online version of this article (10.1007/s12088-020-00916-0) contains supplementary material, which is available to authorized users.