Comparative Genomics, Evolutionary Epidemiology, and RBD-hACE2 Receptor Binding Pattern in B.1.1.7 (Alpha) and B.1.617.2 (Delta) Related to Their Pandemic Response in UK and India

BACKGROUND: The massive increase in COVID-19 infection had generated a second wave in India during May-June 2021 with a critical pandemic situation. The Delta variant (B.1.617.2) was a significant factor during the second wave. Conversely, the UK had passed through the crucial phase of the pandemic from November to December 2020 due to B.1.1.7. The study tried to comprehend the pandemic response in the UK and India to the spread of the B.1.1.7 (Alpha, UK) variant and B.1.617.2 (Delta, India) variant. METHODS: This study was performed in three directions to understand the pandemic response of the two emerging variants. First, we served comparative genomics, such as genome sequence submission patterns, mutational landscapes, and structural landscapes of significant mutations (N501Y, D614G, L452R, E484Q, and P681R). Second, we performed evolutionary epidemiology using molecular phylogenetics, scatter plots of the cluster evaluation, country-wise transmission pattern, and frequency pattern. Third, the receptor binding pattern was analyzed using the Wuhan reference strain and the other two variants. RESULTS: The study analyzed the country-wise and region-wise genome sequences and their submission pattern, molecular phylogenetics, scatter plot of the cluster evaluation, country-wise geographical distribution and transmission pattern, frequency pattern, entropy diversity, and mutational landscape of the two variants. The structural pattern was analyzed in the N501Y, D614G L452R, E484Q, and P681R mutations. The study found increased molecular interactivity between hACE2-RBD binding of B.1.1.7 and B.1.617.2 compared to the Wuhan reference strain. Our receptor binding analysis showed a similar indication pattern for hACE2-RBD of these two variants. However, B.1.617.2 offers slightly better stability in the hACE2-RBD binding pattern through MD simulation than B.1.1.7. CONCLUSION: The increased hACE2-RBD binding pattern of B.1.1.7 and B.1.617.2 might help to increase the infectivity compared to the Wuhan reference strain

Understanding Gene Expression and Transcriptome Profiling of COVID-19: An Initiative Towards the Mapping of Protective Immunity Genes Against SARS-CoV-2 Infection.

The COVID-19 pandemic has created an urgent situation throughout the globe. Therefore, it is necessary to identify the differentially expressed genes (DEGs) in COVID-19 patients to understand disease pathogenesis and the genetic factor(s) responsible for inter-individual variability. The DEGs will help understand the disease's potential underlying molecular mechanisms and genetic characteristics, including the regulatory genes associated with immune response elements and protective immunity. This study aimed to determine the DEGs in mild and severe COVID-19 patients versus healthy controls. The Agilent-085982 Arraystar human lncRNA V5 microarray GEO dataset (GSE164805 dataset) was used for this study. We used statistical tools to identify the DEGs. Our 15 human samples dataset was divided into three groups: mild, severe COVID-19 patients and healthy control volunteers. We compared our result with three other published gene expression studies of COVID-19 patients. Along with significant DEGs, we developed an interactome map, a protein-protein interaction (PPI) pattern, a cluster analysis of the PPI network, and pathway enrichment analysis. We also performed the same analyses with the top-ranked genes from the three other COVID-19 gene expression studies. We also identified differentially expressed lncRNA genes and constructed protein-coding DEG-lncRNA co-expression networks. We attempted to identify the regulatory genes related to immune response elements and protective immunity. We prioritized the most significant 29 protein-coding DEGs. Our analyses showed that several DEGs were involved in forming interactome maps, PPI networks, and cluster formation, similar to the results obtained using data from the protein-coding genes from other investigations. Interestingly we found six lncRNAs (TALAM1, DLEU2, and UICLM CASC18, SNHG20, and GNAS) involved in the protein-coding DEG-lncRNA network; which might be served as potential biomarkers for COVID-19 patients. We also identified three regulatory genes from our study and 44 regulatory genes from the other investigations related to immune response elements and protective immunity. We were able to map the regulatory genes associated with immune elements and identify the virogenomic responses involved in protective immunity against SARS-CoV-2 infection during COVID-19 development

Recurrent anterior shoulder dislocation with glenoid fracture managed by modified Boytchev procedure: a rare case report

Surgical procedures for recurrent anterior dislocation of the shoulder include using capsuloligamentous or bone blocks to create barriers and active interventions using muscle actions. Fracture of glenoid acts as a barrier for bone block procedures. Boytchev procedure, though outmoded, yet acts as simple and effective procedure in this condition. Here we report a 44 year old male with recurrent anterior dislocation with glenoid fracture treated by Boytchev procedure. The patient is on regular follow up since 3 years with no episode of shoulder dislocation till now with full range of movements. To conclude, Boytchev procedure is technically simple and effective method in patients with recurrent anterior shoulder dislocation with fracture of glenoid

Sclerostin-Mediated Impaired Osteogenesis by Fibroblast-Like Synoviocytes in the Particle-Induced Osteolysis Model

Engineered biomaterials are envisioned to replace, augment, or interact with living tissues for improving the functional deformities associated with end-stage joint pathologies. Unfortunately, wear debris from implant interfaces is the major factor leading to periprosthetic osteolysis. Fibroblast-like synoviocytes (FLSs) populate the intimal lining of the synovium and are in direct contact with wear debris. This study aimed to elucidate the effect of Ti particles as wear debris on human FLSs and the mechanism by which they might participate in the bone remodeling process during periprosthetic osteolysis. FLSs were isolated from synovial tissue from patients, and the condition medium (CM) was collected after treating FLSs with sterilized Ti particles. The effect of CM was analyzed for the induction of osteoclastogenesis or any effect on osteogenesis and signaling pathways. The results demonstrated that Ti particles could induce activation of the NFκB signaling pathway and induction of COX-2 and inflammatory cytokines in FLSs. The amount of Rankl in the conditioned medium collected from Ti particle–stimulated FLSs (Ti CM) showed the ability to stimulate osteoclast formation. The Ti CM also suppressed the osteogenic initial and terminal differentiation markers for osteoprogenitors, such as alkaline phosphate activity, matrix mineralization, collagen synthesis, and expression levels of Osterix, Runx2, collagen 1α, and bone sialoprotein. Inhibition of the WNT and BMP signaling pathways was observed in osteoprogenitors after the treatment with the Ti CM. In the presence of the Ti CM, exogenous stimulation by WNT and BMP signaling pathways failed to stimulate osteogenic activity in osteoprogenitors. Induced expression of sclerostin (SOST: an antagonist of WNT and BMP signaling) in Ti particle–treated FLSs and secretion of SOST in the Ti CM were detected. Neutralization of SOST in the Ti CM partially restored the suppressed WNT and BMP signaling activity as well as the osteogenic activity in osteoprogenitors. Our results reveal that wear debris–stimulated FLSs might affect bone loss by not only stimulating osteoclastogenesis but also suppressing the bone-forming ability of osteoprogenitors. In the clinical setting, targeting FLSs for the secretion of antagonists like SOST might be a novel therapeutic approach for preventing bone loss during inflammatory osteolysis

Predictability of STOP-Bang Questionnaire and Epworth Sleepiness Scale in Identifying Obstructive Sleep Apnoea against Polysomnography: A Cross-sectional Study

Introduction: Rising morbidty resulting from Obstructive Sleep Apnoea (OSA) is an emerging public health concern. The estimated prevalence of OSA in India has been investigated. STOP-Bang and Epworth Sleepiness Scale (ESS) have proven beneficial in identifying sleep breathing disorder. Validity of these questionnaire has been verified against polysomnography in many studies. Aim: To assess the predictive ability of STOP-Bang questionnaire and ESS in identifying OSA and comparing their efficacy with polysomnography. Materials and Methods: The cross-sectional study was conducted in the Department of Respiratory Medicine, Government Medical College, Kota, Rajasthan, India, from January 2020 to June 2021, among 100 patients with symptoms of OSA. The STOP-Bang questionnaires were administered to the patients, and scoring was done, followed by overnight attended polysomnography. The normality of data was tested by Shapiro Wilk’s test. The values obtained were statistically analysed and to compare the parameters between groups and with in groups for normal data parametric test One-way Analysis of Variance (ANOVA) followed by Tukey’s HSD test, for intragroup Paired t-test. Results: Mean age of the study population was 49.46±6.523 years, 79 were males and 21 females. Total, 79% of the subjects were males, and 21% of the study subjects were females. Among the 100, 65% had OSA as per polysomnography. STOP-Bang questionnaire had a higher sensitivity as compared to ESS in predicting OSA (75.38% for STOP-Bang and 72.31% for ESS). Conversely, the specificity of ESS (82.8%) was found to be greater than STOP-Bang (45.71%). Similar results were obtained for positive predictive value, in which ESS scored 88.6% while STOP-Bang scored 50%. For negative predictive values, ESS again scored higher (65%) than STOP-Bang (61.7%). Similarly, the Likelihood Ratio for a positive result (LR+) of ESS was greater than STOP-Bang (4.2 and 1.3 respectively). The STOP-Bang questionnaire, however, had higher Likelihood Ratio for a negative test (LR-) as compared to ESS (0.5 and 0.3 respectively). Conclusion: Polysomnography is the gold standard to diagnose OSA. For screening OSA, patients with symptoms of sleep disordered breathing, this study found that STOP-Bang questionnaire is better in identifying OSA as compared to ESS

Usage Pattern of Glimepiride/Metformin Fixed-dose Combination in Type 2 Diabetes Patients with CVD or at Risk of CVD: An Experience in Indian Setting

Background: Diabetes is associated with almost twofold increased risk of cardiovascular diseases (CVD). The present case-based questionnaire survey evaluated the treatment pattern and clinical experience of healthcare professionals in prescribing glimepiride/metformin fixed-dose combination (FDC) to type 2 diabetes mellitus (T2DM) patients with CVD or those patients who are at risk of CVD in the Indian settings. Material and methods: A retrospective, multicenter, observational, case-based questionnaire survey was conducted in Indian healthcare centers using medical records of patients having T2DM, with CVD or are at risk of CVD, who were prescribed any strength of glimepiride/metformin FDC. Data was collected from the patients’ medical records and was analyzed using statistical tests. Results: A total of 680 patients with T2DM with CVD or at risk of CVD were included in this study. Mean duration of diabetes in the patients was 5.7 ± 4.8 years. About 68.5% patients had hypertension, 47.9% had dyslipidemia, 25.4% had coronary artery disease (CAD), 3.6% had transient ischemic attack (TIA), 4.8% had peripheral arterial disease (PAD) and 2.9% had heart failure. Around 18.1% patients had CVD after diabetes was diagnosed, while 81.9% presented with cardiovascular (CV) issues at the time of diabetes diagnosis. All patients received glimepiride/metformin FDC as first-line therapy. About 68.2% patients on glimepiride/metformin FDC had blood pressure within optimal limits. A large proportion of patients had improvement in glycemic parameters. Weight change was noted in 18.4% of the patients overall. Of these, 59.2% had reduction in weight. There were no major adverse events and treatment efficacy and tolerability were reported as good to excellent for 94.6% and 92.9% patients, respectively. Conclusion: This case-based questionnaire survey demonstrates the usage pattern of various strengths of glimepiride/metformin FDC and the clinicians’ practice approach regarding early initiation of this combination in Indian patients with diabetes who have or are at risk of CVD

Comparison of the Success of Two Techniques for the Endotracheal Intubation with C-MAC Video Laryngoscope Miller Blade in Children: A Prospective Randomized Study

Background. Ease of endotracheal intubation with C-MAC video laryngoscope (VLS) with Miller blades 0 and 1 has not been evaluated in children. Methods. Sixty children weighing 3-15 kg with normal airway were randomly divided into two groups. Intubation was done with C-MAC VLS Miller blade using either nonstyletted endotracheal tube (ETT) (group WS) or styletted ETT (group S). The time for intubation and total procedure, intubation attempts, failed intubation, blade repositioning or external laryngeal maneuver, and complications were recorded. Results. The median (minimum/maximum) time for intubation in group WS and group S was 19.5 (9/48) seconds and 13.0 (18/55) seconds, respectively ( = 0.03). The median (minimum/maximum) time for procedure in group WS was 30.5 (18/72) seconds and in group S was 24.5 (14/67) seconds, respectively ( = 0.02). Intubation in first attempt was done in 28 children in group WS and in 30 children in group S. Repositioning was required in 14 children in group WS and in 7 children in group S ( = 0.06). There were no failure to intubate, desaturation, and bradycardia in both groups. Conclusion. Styletted ETT significantly reduces time for intubation and time for procedure in comparison to nonstyletted ETT

Comparison of the Success of Two Techniques for the Endotracheal Intubation with C-MAC Video Laryngoscope Miller Blade in Children: A Prospective Randomized Study

Background. Ease of endotracheal intubation with C-MAC video laryngoscope (VLS) with Miller blades 0 and 1 has not been evaluated in children. Methods. Sixty children weighing 3–15 kg with normal airway were randomly divided into two groups. Intubation was done with C-MAC VLS Miller blade using either nonstyletted endotracheal tube (ETT) (group WS) or styletted ETT (group S). The time for intubation and total procedure, intubation attempts, failed intubation, blade repositioning or external laryngeal maneuver, and complications were recorded. Results. The median (minimum/maximum) time for intubation in group WS and group S was 19.5 (9/48) seconds and 13.0 (18/55) seconds, respectively (p=0.03). The median (minimum/maximum) time for procedure in group WS was 30.5 (18/72) seconds and in group S was 24.5 (14/67) seconds, respectively (p=0.02). Intubation in first attempt was done in 28 children in group WS and in 30 children in group S. Repositioning was required in 14 children in group WS and in 7 children in group S (p=0.06). There were no failure to intubate, desaturation, and bradycardia in both groups. Conclusion. Styletted ETT significantly reduces time for intubation and time for procedure in comparison to nonstyletted ETT

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy