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Author(s): RP Sangeetha [1]; Dhritiman Chakrabarti [1]; Kamath Sriganesh (corresponding author) [1]; Musumur Mahendranath [1]; Sathyaprabha TN [2]; Dwarakanath Srinivas [3] INTRODUCTION The autonomic nervous system (ANS) is crucial for [...], Background and Aims: The autonomic nervous system (ANS) is cardinal for systemic homeostasis. Autonomic dysfunction is prevalent in as high as 65% of patients presenting for cardiac surgery in the Indian scenario. Pre-existing cardiac autonomic dysfunction (CAD) in surgical patients can accentuate perioperative haemodynamic fluctuations during stressful intraoperative events, predispose to adverse cardiac events, and contribute to morbidity and mortality. The prevalence and predictors of CAD in the elective neurosurgical population are unknown in the Indian scenario. The current study was conducted to bridge this knowledge gap. Methods: In this single-centre prospective observational study conducted at a tertiary care neurosciences centre, among 400 consenting adult patients of either gender, between 18 and 80 years of age, undergoing elective neurosurgery, the preoperative ANS function at the bedside was assessed as the primary outcome measure. The ANS status was evaluated using ANSiscope™-derived indices of heart rate variability. The diagnosis of CAD was made when the ANS index exceeded a threshold of 13.5. Data regarding predictors of CAD were collected from patient records as the secondary outcome measure. Statistical analysis was done using the R software. A P-value of Results: The prevalence of preoperative CAD in our study population was 79.7% (319/400 patients). None of the demographic and baseline clinical characteristics we studied predicted CAD in our study. Conclusion: We observed a significant prevalence of preoperative CAD among elective neurosurgical patients. None of the parameters we evaluated predicted CAD in our study. Keywords: Dysautonomia, neurosurgery, perioperative, prevalence

Targeting the class A Beta lactamases Omega loop is an ideal way to combat drug resistance because of its significant role in the catalytic activity and deacylation process inhibition. Therefore, the molecular docking approach with computerized peptide-based in silico screening has been applied for the identification of inhibitors of TEM-type βLs. Among the subjected 105 peptides, Chrombacin (-47.8 KJ/mol), Gassericin A (-35.7 KJ/mol), Duramycin (-34.1 KJ/mol), Brevinin-1DYa (-34.0 KJ/mol), Amoebapore A (-31.2 KJ/mol), Mundticin ATO6 (-29.0 KJ/mol), Lactocyclicin Q (-26.3 KJ/mol), Cinnamycin (-25.9 KJ/mol showed highest binding energy. Among the peptides that showed the highest docking score Elafin, Cinnamycin, Duramycin interacted with Lys 73 of the α domain of catalytic residues of TEM-1 Beta lactamases, whereas Taromycin A, Gassericin A interacted with Lys 234 of the β domain, depicting a strong inhibition and also exhibited desirable physicochemical properties. Hence further in vitro examination of these cyclic peptides against the resistant strains is warranted to help design further novel inhibitors based on their scaffolds and also for the development of an effective drug combination regime.

Background: Individuals with inborn errors of immunity (IEI) have an increased risk of developing malignancies compared to their peers. We report a case of Hodgkin lymphoma in an adolescent with CD27 deficiency. Case report: A 15-year-old girl presented with cervical swelling and breathlessness for 3 days. Her past history was remarkable, with a history of recurrent respiratory infections. On examination, she had grade 2 clubbing, bilateral cervical lymphadenopathy, hepatosplenomegaly, and bilateral coarse crepitations. Biopsy showed overlapping immunomorphological features of classic Hodgkin lymphoma (HL), with features intermediate between diffuse large B-cell lymphoma and HL. A staging PET-CT revealed a stage III disease and bronchiectatic changes in bilateral lungs. The serum immunoglobulin levels showed hypogammaglobulinemia. Next generation sequencing demonstrated a homozygous missense variant in the CD27 gene (c.319C>T; p.Arg107Cys). She was treated with ABVD/COPDac chemotherapy along with supportive care. She is currently 16 months post-treatment. Conclusion: CD 27 deficiency is a rare IEI with a common variable immunodeficiency phenotype and a high propensity to develop lymphomas. Clinical suspicion, early detection, and management are warranted to prevent complications and mortality.

Hepatitis B infection is a common disease worldwide. Hepatitis B is one of the leading cause of malignancy and cirrhosis of liver. The diagnosis of Hepatitis B Virus (HBV) infection is mainly made through detection of serological markers. Our study aimed to detect presence of Hepatitis B Precore Antigen (HBeAg) and Antibodies to Hepatitis B core Antigen (HBcAg) among Hepatitis B Surface Antigen (HBsAg) positive samples detected in Microbiology laboratory during the study period. HBeAg, Total Anti HBc and Anti HBcIgM was detected using ELISA (DIA.PRO – ITALY) and patients were categorized based on presence of HBeAg, Total Anti HBc and Anti HBcIgM. Out of 180 samples tested positive for HBsAg, majority belonged to the age group of 41-60 years. With regard to gender, males were found to be majority and four percent were antenatal women. HBeAg was found in 20.6% patients indicating high infectivity. Out of 180 samples, 9.45% were found to have acute infection and 90.55% were with chronic infection. Among the patients with acute infection, 58.8% had high infectivity whereas in patients with chronic infection 16.56% had high infectivity. HBV Screening and categorization of positive patients are important to prevent chronic hepatitis, its complications among infected patients and to reduce the transmission of HBV in the community.

Introduction: Supraclavicular approaches serve as a common method for administering regional anesthesia in upper limb procedures. In improving the impact with a length of pain relief, medical professionals frequently include additional substances such as dexmedetomidine, buprenorphine, dexamethasone, clonidine, sodium bicarbonate, and tramadol alongside local anesthetics. The intent of this study was to evaluate its impact of incorporating buprenorphine and dexmedetomidine into ropivacaine 0.5%. Materials and Methods: The trial of 90 patients between the ages of 18 and 60, who were identified as American Society of Anesthesiologists Grade 1 and 2, and scheduled upper limb surgery using the supraclavicular approach, were included. They were assigned into distinct groups, each of the groups consisting of thirty individuals. Group R was administered anesthesia consisting of 25 ml of ropivacaine 0.5% along with 1 ml of saline. Group B was administered anesthetics containing ropivacaine 0.5% and buprenorphine, which was diluted in saline. Group D was administered a solution containing ropivacaine 0.5% and dexmedetomidine, which was diluted in saline. Results: Group D had an earlier sensory blockade onset (8.25 min) compared to Group B (9.64 min) and Group R (12.89 min). Group D demonstrated a notably quicker motor blockade onset (9.21 min) in contrast to Group B (12.07 min) and Group R (15.03 min). In contrast with the other groups, Group D exhibited a more longer time frame of both sensory and motor blockades and also an extended period of anesthesia after the surgery. Conclusion: Dexmedetomidine was a more effective adjuvant over buprenorphine in the brachial plexus blocks. This resulted in significantly lower postoperative pain scores at 407.67 min and 612.32 min for the plain ropivacaine and buprenorphine groups, respectively.

Background: Self-directed learning (SDL) is an internationally accepted principle of adult education. CBME curriculum implemented by the Government of India has allotted 280 hours of SDL in all subjects for undergraduate medical students. SDL is yet to root into the student community as norms and a definitive program evaluation is still not in shape. Aim and Objective: To identify students’ readiness and perceived barriers towards SDL. Materials and Methods: This questionnaire-based study was conducted between January 2023 to May 2023 among faculties and students. The 12 items of self-directed learning readiness instrument were adopted from Shen et al. Results: A total of 480 MBBS students participated. 97.7% of students were aware of SDL in their first year. The highest score was in the “self-monitoring” domain (Mean ± SD = 3.89 ± 0.64) and the lowest score was in “Planning and Implementation” (3.56 ± 0.80). Students perceived that SDL would enhance their communication (50.41%), critical thinking (49.2%), problem solving (40.4%), research (39.8%) and cognitive skills (37.1%). Among barriers the most significant was lack of guidance and resource deficiency (30.4%, 29%). In this study 52 CISP completed faculty participated and 82.69% agreed students were ready for SDL. The suggested resource materials were reference books and online materials (90.38% & 26.92%). Conclusion: Medical students’ readiness for SDL is quite encouraging which was also attested by 83% of faculty. Given the fertile nidus of growing young minds if deficiencies are addressed, the medical curriculum would be fortified with SDL ensuring long term benefits.

Molecular docking (Mol.Doc) approach of an azo-ester based fluorophore (AEF) with widely studied proteins like Human serum Albumin (HSA), Bovine serum Albumin (BSA), Beta lactoglobin (βLG) and Ovalbumin (OVA) were carried out. The binding affinity and strength of AEF-HSA complex is due to hydrogen-bonding (h-bonding) and hydrophobic interactions (predominantly attributed to pi-alkyl). AEF and HSA acts as h-bonding acceptor as well as donor. The energetically favored conformers of AEF-HSA complex are governed and stabilized by polar as well as non-polar amino acids. On the contrary, the pattern observed in all the conformers of AEF-BSA, AEF- βLG and AEF-OVA are energetically least favored (+ve ∆G) compared to that of HSA. The least binding affinity of AEF is towards OVA (Binding energy (BE) +581.15 Kcalmol−1 followed by βLG (+55.11) and BSA (+12.12) . Though BSA and HSA are structurally similar to each other, they vary in the binding stability with AEF. This is attributed to several unfavorable interactions that destabilize AEF-BSA complex which was not resulted in the complex existing between AEF-HSA. The energetically least stable complexes (AEF-BSA, AEF-βLG and AEF-OVA) are predominantly governed by hydrophobic interactions. However, several h-bonding interactions along with pi-sigma/pi-pi/pi-alkyl interactions result in destabilization of the above complexes. Interestingly, AEF-HSA complex stability is attributed to fewer number of hydrophobic interactions along with h-bonding interactions. The h-bonding interaction governs the stability of the complex which is the driving force. Docking studies illustrates that the binding of amino acids (AAs) in various subdomains play a significant role on the binding nature. The stability of AEF-HSA over other protein complexes in terms of BE is emphasized in the study. The energetically stable sites and sub-domains of AEF with HSA and BSA establish the site selective and site-specific nature of AEF with proteins. In silico studies provide an excellent and easier approach in establishing the molecular interactions existing between AEF with globular proteins. ADMET parameters of the guest molecule calculated exemplifies that AEF compound is less toxic and possesses high oral bioavailability. Based on the binding efficiency of AEF with albumins, the ADMET properties and drug likeliness approach of AEF provides an information on the application towards proteins in the concept of medicine and chemistry.

Non-Collusive Interest Flooding Attacks (NCIFA) disrupt Named Data Networks' (NDNs) seamless communication and content distribution through QoS degradation. This work proposes 2TierEdge-Defense: a framework based on Long Short Term Memory (LSTM) to detect NCIFA in NDN at the edge content routers. The framework has been evaluated on large-scale Rocketfuel topologies for AT&T Internet Service Provider. The 2TierEdge-Defense framework consists of attack detection and mitigation modules with detection at edge router and their interfaces. During offline training and evaluation, the 2TierEdge-Defense framework can detect NCIFA with 0.92 (F1-score) and 0.84 (F1-score) at edge routers and their interfaces, respectively, with cascaded F1-score of 0.9872. Upon detection, the mitigation strategy in the 2TierEdge-Defense framework can improve the QoS metrics as quickly as in 0.45 seconds with an overall F1 score as high as 0.9872. The 2TierEdge-Defense is evaluated for scalability topology scenarios to ensure better performance when deployed on NDN content routers with a cascaded miss rate of 0.1 and a false alarm rate of 0.07.

Typhoid fever is a bacterial infection that can be fatal and a major concern globally. Due to the infection’s high morbidity and fatality rates, there is an urgent need for precise and quick diagnostic tests to help with disease management and prevention. The purpose of the current review is to evaluate the specificity and sensitivity of the currently commercially available typhoid fever rapid diagnostic kits (RDTs). Publicly available English databases, such as PubMed and Google Scholar, were used to screen the research papers. We mined a total of 371 research documents, of which 18 articles were selected based on the inclusion and exclusion criteria. Studies from 10 different developing countries evaluated the diagnostic performance of Typhidot, Typhidot-M, and Tubex. The average sensitivity and specificity were approximately 80%–90% and 65%–78% for Typhidot, 85%–94% and 77%–89% for Typhidot-M, and 94.7% and 80.4% for Tubex. The sensitivity and specificity of these diagnostics varied with the geographical location. In comparison to the widely used Widal test, the observed performance cannot support the exclusive use of a particular RDT. Hence, there is a need to develop affordable, antigen-based RDTs.

Background: Metabolic syndrome has increased globally due to sedentary lifestyles, unhealthy diets and obesity, which is posing a substantial burden on healthcare systems. Understanding the determinants of metabolic syndrome like lifestyle factors, socioeconomic status and the environment are vital for devising effective prevention and management. Research into these determinants helps to identify high-risk populations and develop interventions to reduce its occurrence. Objectives: i. To estimate the prevalence of metabolic syndrome among the adult population. ii. To determine the factors associated with metabolic syndrome among the adult population. Methodology: A cross-sectional study was carried out among 410 adults (≥18 years). A semi-structured questionnaire was used to collect data and National Cholesterol Education Program’s Adult Treatment Panel III criteria was used to diagnose metabolic syndrome. Continuous and categorical data were represented as mean and proportion, respectively. The strength of the association was determined using the prevalence ratio and adjusted prevalence ratio. Results: The mean age of the participants was 44.97 ± 14.7, about 58.3% of them were females. Metabolic syndrome prevalence was 39.8%. Multivariate regression analysis demonstrated that being over 40 years old, marital status, higher socioeconomic status, skilled workers, physical inactivity and obesity were independently linked to metabolic syndrome. Conclusions: The burden can be reduced by identifying the risk factors at the early stage through screening and by adopting a healthy lifestyle.

Lockdowns were implemented in nearly all countries in the world in order to reduce the spread of COVID-19. The majority of the production activities like industries, transportation, and construction were restricted completely. This unprecedented stagnation of resident's consumption and industrial production has efficiently reduced air pollution emissions, providing typical and natural test sites to estimate the effects of human activity controlling on air pollution control and reduction. Air pollutants impose higher risks on the health of human beings and also damage the ecosystem. Previous research has used machine learning (ML) and statistical modeling to categorize and predict air pollution. This study developed a binary spring search optimization with hybrid deep learning (BSSO-HDL) for air pollution prediction and an air quality index (AQI) classification process during the pandemic. At the initial stage, the BSSO-HDL model pre-processes the actual air quality data and makes it compatible for further processing. In the presented BSSO-HDL model, an HDL-based air quality prediction and AQI classification model was applied in which the HDL was derived by the use of a convolutional neural network with an extreme learning machine (CNN-ELM) algorithm. To optimally modify the hyperparameter values of the BSSO-HDL model, the BSSO algorithm-based hyperparameter tuning procedure gets executed. The experimental outcome demonstrates the promising prediction classification performance of the BSSO-HDL model. This model, developed on the Python platform, was evaluated using the coefficient of determination R2, the mean absolute error (MAE), and the root mean squared error (RMSE) error measures. With an R2 of 0.922, RMSE of 15.422, and MAE of 10.029, the suggested BSSO-HDL technique outperforms established models such as XGBoost, support vector machines (SVM), random forest (RF), and the ensemble model (EM). This demonstrates its ability in providing precise and reliable AQI predictions.

Author(s): Himanshu Jog [1]; Divya Nagabushana (corresponding author) [1]; Sangeetha Shenoy [2]; Namita Ravikumar [2]; A R Somashekhar [2] Sir, Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently described [...]

Methyl-coenzyme M reductase (MCR) catalyzes the formation of methane, and its activity accounts for nearly all biologically produced methane released into the atmosphere. The assembly of MCR is an intricate process involving the installation of a complex set of posttranslational modifications and the unique Ni-containing tetrapyrrole called coenzyme F430. Despite decades of research, details of MCR assembly remain largely unresolved. Here, we report the structural characterization of MCR in two intermediate states of assembly. These intermediate states lack one or both F430 cofactors and form complexes with the previously uncharacterized McrD protein. McrD is found to bind asymmetrically to MCR, displacing large regions of the alpha subunit and increasing active-site accessibility for the installation of F430-shedding light on the assembly of MCR and the role of McrD therein. This work offers crucial information for the expression of MCR in a heterologous host and provides targets for the design of MCR inhibitors.

PurposeThere is a growing interest in extracellular vesicles (EVs) for ocular applications as therapeutics, biomarkers, and drug delivery vehicles. EVs secreted from mesenchymal stem cells (MSCs) have shown to provide therapeutic benefits in ocular conditions. However, very little is known about the properties of bioreactor cultured-3D human retinal organoids secreted EVs. This study provides a comprehensive morphological, nanomechanical, molecular, and proteomic characterization of retinal organoid EVs and compares it with human umbilical cord (hUC) MSCs.MethodsThe morphology and nanomechanical properties of retinal organoid EVs were assessed using Nanoparticle tracking analysis (NTA) and Atomic force microscopy (AFM). Gene expression analysis of exosome biogenesis of early and late retinal organoids were compared using qPCR. The protein profile of the EVs were analyzed with proteomic tools.ResultsNTA indicated the average size of EV as 100-250 nm. A high expression of exosome biogenesis genes was observed in late retinal organoids EVs. Immunoblot analysis showed highly expressed exosomal markers in late retinal organoids EVs compared to early retinal organoids EVs. Protein profiling of retinal organoid EVs displayed a higher differential expression of retinal function-related proteins and EV biogenesis proteins than hUCMSC EVs, implicating that the use of retinal organoid EVs may have a superior therapeutic effect on retinal disorders.ConclusionThis study provides supplementary knowledge on the properties of retinal organoid EVs and suggests their potential use in the diagnostic and therapeutic treatments for ocular diseases.