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Objective: Diabetic foot ulcers (DFU) are a major sequela of uncontrolled diabetes with a high risk of adverse outcomes. Poor DFU outcomes disproportionately impact patients living in rural and economically distressed communities with lack of access to consistent, quality care. This study aimed to analyze the risk of geographic and economic disparities, including rural status and county economic distress, on the disease burden of DFU at presentation utilizing the SVS WIfI classification system., Methods: We conducted a retrospective review of 454 patients diagnosed with a DFU from 2011 to 2020 at a single institution's inpatient and outpatient wound care service. Patients >18 years old, with type II diabetes mellitus, and diabetic foot ulcer were included., Results: ANCOVA analyses showed rural patients had significantly higher WIfI composite scores (F(1,451) = 9.61, p = .002), grades of wound (F(1,439) = 11.03, p = .001), and ischemia (F(1,380) = 12.574, p = .001) compared to the urban patients. Patients that resided in at-risk economic counties had significantly higher overall WIfI composite scores (F(2,448) = 3.31, p = .037) than patients who lived in transitional economic counties, and higher foot infection grading (F(2,440) = 3.02, p = .05) compared to patients who lived in distressed economic counties. DFU patients who resided in distressed economic counties presented with higher individual grades of ischemia (F(2, 377) = 3.14, p = .04) than patients in transitional economic counties. Chi-Square analyses demonstrated patients who resided in urban counties were significantly more likely to present with grade 1 wounds (χ2(3) = 9.86, p = .02) and grade 0 ischemia (χ2(3) = 16.18, p = .001) compared to patients in rural areas. Economically distressed patients presented with significantly less grade 0 ischemia compared to patients in transitional economic counties (χ2(6) = 17.48, p = .008)., Conclusions: Our findings are the first to demonstrate the impact of geographic and economic disparities on the disease burden of DFU at presentation utilizing the SVS WIfI classification system. This may indicate need for improved multidisciplinary primary care prevention strategies with vascular specialists in these communities to mitigate worsening DFU and promote early intervention., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Optimum formulation of Biological-E's protein subunit CORBEVAX™ vaccine was selected in phase-1 and -2 studies and found to be safe and immunogenic in healthy adult population. This is a phase-3 prospective, single-blinded, randomized, active controlled study conducted at 18 sites across India in 18-80 year-old subjects. This study has two groups; (i) immunogenicity-group, participants randomized either to CORBEVAX™ ( n  = 319) or COVISHIELD™ arms ( n  = 320). (ii) Safety-group containing single CORBEVAX™ arm ( n  = 1500) and randomization is not applicable. Healthy adults without a history of COVID-19 vaccination or SARS-CoV-2 infection were enrolled into immunogenicity arm and subjects seronegative to SARS-CoV-2 infection were enrolled into the safety arm. The safety profile of CORBEVAX™ vaccine was comparable to the comparator vaccine COVISHIELD™. Majority of reported AEs were mild in nature in both arms. The CORBEVAX™ to COVISHIELD™ GMT-ratios at day-42 time-point were 1·15 and 1·56 and the lower limit of the 95% confidence interval for the GMT-ratios was determined as 1·02 and 1·27 against Ancestral and Delta strains of SARS-COV-2 respectively. Both COVISHIELD™ and CORBEVAX™ vaccines showed comparable seroconversion post-vaccination against anti-RBD-IgG response. The subjects in CORBEVAX™ cohort also exhibited higher interferon-gamma secreting PBMC's post-stimulation with SARS-COV-2 RBD-peptides than subjects in COVISHIELD™ cohort.

Background: After establishing safety and immunogenicity of Biological-E's CORBEVAX™ vaccine in adult population (18-80 years) in Phase 1-3 studies, vaccine is further tested in children and adolescents in this study., Methods: This is a phase-2/3 prospective, randomised, double-blind, placebo-controlled study evaluating safety, reactogenicity, tolerability and immunogenicity of CORBEVAX™ vaccine in children and adolescents of either gender between <18 to ≥12 years of age in Phase-2 and <18 to ≥5 years of age in Phase-Phase-2/Phase-3 with placebo as a control. This study has two age sub-groups; subgroup-1 with subjects <18 to ≥12 years of age and subgroup-2 with subjects <12 to ≥5 years of age. In both sub groups, eligible subjects (SARS-CoV-2 RT-PCR negative and seronegative at baseline) were randomized to receive either CORBEVAX™ vaccine or Placebo in 3:1 ratio., Findings: The safety profile of CORBEVAX™ vaccine in both pediatric cohorts was comparable to the placebo-control group. Majority of reported adverse events (AEs) were mild in nature. No severe or serious-AEs, medically attended AEs (MAAEs) or AEs of special interest (AESI) were reported during the study period and all reported AEs resolved without any sequelae. In both pediatric age groups, CORBEVAX™ vaccinated subjects showed significant improvement in humoral immune-responses in terms of anti-RBD-IgG concentrations, anti-RBD-IgG1 titers, neutralizing-antibody (nAb)-titers against Ancestral-Wuhan and Delta-strains. Significantly high interferon-gamma immune- response (cellular) was elicited by CORBEVAX™ vaccinated subjects with minimal effect on IL-4 cytokine secretion., Interpretations: The safety profile of CORBEVAX™ vaccine in <18 to ≥5 years' children and adolescents was found to be safe and tolerable. Significant increase in anti-RBD-IgG and nAb-titers and IFN-gamma immune-responses were observed post-vaccination in both pediatric age sub-groups. The nAb titers observed in both the pediatric age cohorts were non-inferior to the adult cohort (BECT069 study) in terms of ratio of the GMT's of both the cohorts. This study shows that CORBEVAX™ vaccine is highly immunogenic and can be safely administered to pediatric population as young as 5 years old. The study was prospectively registered with clinical trial registry of India- CTRI/2021/10/037066., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ST, VP, SG, VY, RM, PVS, KT, MK, SKM, SA and ASJ are employees of Biological E Limited and they don’t have any incentives or stock options. All other participating authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Being predictors of the mechanical properties of human cortical bone, bound and pore water measurements by magnetic resonance (MR) imaging are being developed for the clinical assessment of fracture risk. While pore water is a surrogate of cortical bone porosity, the determinants of bound water are unknown. Manipulation of organic matrix properties by oxidative deproteinization, thermal denaturation, or nonenzymatic glycation lowers bone toughness. Because bound water contributes to bone toughness, we hypothesized that each of these matrix manipulations affect bound water fraction (V bw /V bone ). Immersing cadaveric bone samples in sodium hypochlorite (NaClO) for 96 hours did not affect tissue mineral density or cortical porosity, but rather decreased V bw /V bone and increased short-T 2 pore water signals as determined by 1 H nuclear MR relaxometry ( 1 H NMR). Moreover, the post treatment V bw /V bone linearly correlated with the remaining weight fraction of the organic matrix. Heating bone samples at 110°C, 120°C, 130°C, and then 140°C (∼24 hours per temperature and rehydration for ∼24 hours before 1 H NMR analysis) did not affect V bw /V bone . After subsequently heating them at 200°C, V bw /V bone increased. Boiling bone samples followed by heating at 110°C, 120°C, and then 130°C in water under pressure (8 hours per temperature) had a similar effect on V bw /V bone . Raman spectroscopy analysis confirmed that the increase in V bw /V bone coincided with an increase in an Amide I subpeak ratio that is sensitive to changes in the helical structure of collagen I. Glycation of bone by ribose for 4 weeks, but not in glucose for 16 weeks, decreased V bw /V bone , although the effect was less pronounced than that of oxidative deproteinization or thermal denaturation. We propose that MR measurements of bound water reflect the amount of bone organic matrix and can be modulated by collagen I helicity and by sugar-derived post translational modifications of the matrix. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.