An immunoinformatic approach for developing a multi-epitope subunit vaccine against Monkeypox virus.

An in-silico approach was implemented to develop a multi-epitope subunit vaccine construct against the recent outbreak of the Monkeypox virus. The contribution of 10 different antigenic proteins based on their antigenicity led to the selection of 10 HTL, 9 CTL, and 6 BCL epitopes. The construct was further investigated for its allergenicity, antigenicity, and physio-chemical properties using servers such as AllerTOP and Allergen FP, VaxiJen and ANTIGENPro, and ProtParam respectively. The secondary structure of the vaccine was predicted using the SOPMA server followed by I-TASSER for the 3D structure. After refinement and validation of structural stability of the modelled vaccine, a molecular docking assay was implemented to study the interaction of the known TLR4 receptor with that of the constructed vaccine using the ClusPro server. The docked vaccine and TLR4 receptor were studied using the molecular dynamics (MD) simulation to validate the stability of the complex. After codon optimization the cDNA was constructed and in-silico cloning of the vaccine construct was carried out. The vaccine was also subjected to computational immune assay which predicted a powerful immune response against the Monkeypox virus validating that the developed multi-epitope vaccine construct can be a potent vaccine candidate. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-024-00220-5.

An Exploratory Research Comparing Oral Health, Pattern of Substance Abuse and Nicotine Dependence among LGBT, Female Sex Workers and Heterogenders.

AIM: Lesbian, gay, bisexual, transgender, and queer (LGBTQ), female sex workers (FSW), and heterogenders are those unconventional groups of the society who are identified with major unacceptance. Thus, the present study is conducted to assess and compare the oral health status, substance abuse pattern and nicotine dependence using Fagerstrom nicotine dependence scale (FNDP) among the LGBTQ, FSW, and heterogender in a defined location of Gautam Buddha Nagar, district in West U.P. MATERIALS AND METHODS: The present exploratory research included three study groups, the LGBTQ, FSW, and heterogenders (HG) residing in the same habitat. Purposive snowball sampling was conducted for the accessibility of the unapproachable population in the defined geographical location at Gautam Budha Nagar, district in West Uttar Pradesh. The data collection of a total of 177 participants was done using a pre-validated, pretested proforma consisting of three different parts including WHO oral health assessment form for adults, 2013, questionnaire regarding pattern of substance abuse and FNDS. Data were recorded and statistically analyzed using SPSS. RESULTS: Prevalence of oral health disorders including dental caries, periodontal disease as well as oral mucosal lesions were more commonly found among the LGBTQ participants followed by FSW and the differences were found to be statistically significant. In context of altered habits, 100% of the participants in the present study were reported with smokeless tobacco habits whereas majority of the FSW were reported with a habit of smoking tobacco. CONCLUSION: In addition to belonging to ethnic and sexual minority, and having minimal or low education status, and low socioeconomic status, the present study groups are reported to have suboptimal access to quality healthcare and are further reported with high level of substance abuse as well as nicotine dependence. CLINICAL SIGNIFICANCE: The present study is an attempt to provide base line data for further research and provide data to the policy makers so as to increase the healthcare access to the present groups. How to cite this article: Sharma S, Shukla S, Kamate SK, et al. An Exploratory Research Comparing Oral Health, Pattern of Substance Abuse and Nicotine Dependence among LGBT, Female Sex Workers and Heterogenders. J Contemp Dent Pract 2023;24(12):991-997.

COVID-19 infection, and reinfection, and vaccine effectiveness against symptomatic infection among health care workers in the setting of omicron variant transmission in New Delhi, India.

Background: Surge of SARS CoV-2 infections ascribed to omicron variant began in December 2021 in New Delhi. We determined the infection and reinfection density in a cohort of health care workers (HCWs) along with vaccine effectiveness (VE) against symptomatic infection within omicron transmission period (considered from December 01, 2021 to February 25, 2022. Methods: This is an observational study from the All India Institute of Medical Sciences, New Delhi. Data were collected telephonically. Person-time at risk was counted from November 30, 2021 till date of infection/ reinfection, or date of interview. Comparison of clinical features and severity was done with previous pandemic periods. VE was estimated using test-negative case-control design [matched pairs (for age and sex)]. Vaccination status was compared and adjusted odds ratios (OR) were computed by conditional logistic regression. VE was estimated as (1-adjusted OR)X100-. Findings: 11474 HCWs participated in this study. The mean age was 36⋅2 (±10⋅7) years. Complete vaccination with two doses were reported by 9522 (83%) HCWs [8394 (88%) Covaxin and 1072 Covishield (11%)]. The incidence density of all infections and reinfection during the omicron transmission period was 34⋅8 [95% Confidence Interval (CI): 33⋅5-36⋅2] and 45⋅6 [95% CI: 42⋅9-48⋅5] per 10000 person days respectively. The infection was milder as compared to previous periods. VE was 52⋅5% (95% CI: 3⋅9-76⋅5, p = 0⋅036) for those who were tested within 14-60 days of receiving second dose and beyond this period (61-180 days), modest effect was observed. Interpretation: Almost one-fifth of HCWs were infected with SARS CoV-2 during omicron transmission period, with predominant mild spectrum of COVID-19 disease. Waning effects of vaccine protection were noted with increase in time intervals since vaccination. Funding: None.

An immediate post op and follow up assessment of circulating adipo-cytokines after bariatric surgery in morbid obesity.

BACKGROUND: Bariatric surgery has emerged as a promising treatment for improving adipose tissue dysfunction in obesity, but the mechanisms for such amelioration are still not known. This study comprehensively explores a panel of adipo-cytokines in individuals with obesity undergoing bariatric surgery, in conjunction with markers of insulin resistance, at three time points i.e., pre-op, immediate post-op and 6 months post-surgery. METHODS: It is a case-control prospective study among obese individuals undergoing bariatric surgery (BMI ≥35 kg/m2, n=30) and non-obese subjects (BMI <25 kg/m2, n=30), comparing the levels of serum adiponectin, resistin, C-Reactive Protein (CRP), Interleukin (IL)-6 and 8, Monocyte chemoattractant protein (MCP)-1 and Tumor necrosis factor (TNF)-α between them. The same were followed at immediate and 6-month post-op periods in the former group. The serum markers were correlated with the markers of Insulin resistance like HOMA-IR, HOMA-ß and QUICKI. RESULTS: A significant increase in adiponectin was seen after weight loss in obese group (17.54 ± 1.31 µg/mL at baseline vs 68.76 ± 1.84 µg/mL at 6- month post-surgery). CRP being an acute phase protein showed significant higher levels at immediate post-op period but declined even below its baseline at 6 months after surgery (33.34 ± 16.85 µg/mL at baseline vs 59.85 ± 23.12 µg/mL at immediate post-op vs 9.66 ± 1.84 µg/mL at 6 months post-operatively). Few inconsistencies were observed in the trajectories of IL-6 and TNF-α, while other pro-inflammatory markers indicated resolution after surgery. CONCLUSION: Bariatric surgery alleviated the systemic inflammation, correlating with improved insulin resistance in individuals with obesity.

SARS-CoV-2 Reinfection Rate and Estimated Effectiveness of the Inactivated Whole Virion Vaccine BBV152 Against Reinfection Among Health Care Workers in New Delhi, India.

Importance: A surge of COVID-19 occurred from March to June 2021, in New Delhi, India, linked to the B.1.617.2 (Delta) variant of SARS-CoV-2. COVID-19 vaccines were rolled out for health care workers (HCWs) starting in January 2021. Objective: To assess the incidence density of reinfection among a cohort of HCWs and estimate the effectiveness of the inactivated whole virion vaccine BBV152 against reinfection. Design, Setting, and Participants: This was a retrospective cohort study among HCWs working at a tertiary care center in New Delhi, India. Exposures: Vaccination with 0, 1, or 2 doses of BBV152. Main Outcomes and Measures: The HCWs were categorized as fully vaccinated (with 2 doses and ≥15 days after the second dose), partially vaccinated (with 1 dose or 2 doses with <15 days after the second dose), or unvaccinated. The incidence density of COVID-19 reinfection per 100 person-years was computed, and events from March 3, 2020, to June 18, 2021, were included for analysis. Unadjusted and adjusted hazard ratios (HRs) were estimated using a Cox proportional hazards model. Estimated vaccine effectiveness (1 - adjusted HR) was reported. Results: Among 15 244 HCWs who participated in the study, 4978 (32.7%) were diagnosed with COVID-19. The mean (SD) age was 36.6 (10.3) years, and 55.0% were male. The reinfection incidence density was 7.26 (95% CI: 6.09-8.66) per 100 person-years (124 HCWs [2.5%], total person follow-up period of 1696 person-years as time at risk). Fully vaccinated HCWs had lower risk of reinfection (HR, 0.14 [95% CI, 0.08-0.23]), symptomatic reinfection (HR, 0.13 [95% CI, 0.07-0.24]), and asymptomatic reinfection (HR, 0.16 [95% CI, 0.05-0.53]) compared with unvaccinated HCWs. Accordingly, among the 3 vaccine categories, reinfection was observed in 60 of 472 (12.7%) of unvaccinated (incidence density, 18.05 per 100 person-years; 95% CI, 14.02-23.25), 39 of 356 (11.0%) of partially vaccinated (incidence density 15.62 per 100 person-years; 95% CI, 11.42-21.38), and 17 of 1089 (1.6%) fully vaccinated (incidence density 2.18 per 100 person-years; 95% CI, 1.35-3.51) HCWs. The estimated effectiveness of BBV152 against reinfection was 86% (95% CI, 77%-92%); symptomatic reinfection, 87% (95% CI, 76%-93%); and asymptomatic reinfection, 84% (95% CI, 47%-95%) among fully vaccinated HCWs. Partial vaccination was not associated with reduced risk of reinfection. Conclusions and Relevance: These findings suggest that BBV152 was associated with protection against both symptomatic and asymptomatic reinfection in HCWs after a complete vaccination schedule, when the predominant circulating variant was B.1.617.2.

Tapping the Potential of Multimodal Non-invasive Brain Stimulation to Elucidate the Pathophysiology of Movement Disorders.

This mini-review provides a detailed outline of studies that have used multimodal approaches in non-invasive brain stimulation to investigate the pathophysiology of the three common movement disorders, namely, essential tremor, Parkinson's disease, and dystonia. Using specific search terms and filters in the PubMed® database, we finally shortlisted 27 studies in total that were relevant to this review. While two-thirds (Brittain et al., 2013) of these studies were performed on Parkinson's disease patients, we could find only three studies that were conducted in patients with essential tremor. We clearly show that although multimodal non-invasive brain stimulation holds immense potential in unraveling the physiological mechanisms that are disrupted in movement disorders, the technical challenges and pitfalls of combining these methods may hinder their widespread application by movement disorder specialists. A multidisciplinary team with clinical and technical expertise may be crucial in reaping the fullest benefits from such novel multimodal approaches.

Improvements in cholesterol efflux capacity of HDL and adiponectin contribute to mitigation in cardiovascular disease risk after bariatric surgery in a cohort with morbid obesity.

BACKGROUND: Bariatric surgery can alleviate cardiovascular risk via effects on cardiovascular disease (CVD) risk factors such as diabetes mellitus, hypertension, and dyslipidemia. Our study aimed to assess the cholesterol efflux capacity (CEC) of HDL as a negative risk factor for CVD in individuals with obesity and identify the factors associated with improvement in CEC 3 months following bariatric surgery. METHODS: We recruited 40 control individuals (mean BMI of 22.2 kg/m2) and 56 obese individuals (mean BMI of 45.9 kg/m2). The biochemical parameters, inflammatory status and CEC of HDL was measured for the obese individuals before bariatric surgery and at 3 months after surgery. The CEC was measured using a cell-based cholesterol efflux system of BODIPY-cholesterol-labelled THP-1 macrophages. RESULTS: A significant reduction in BMI (- 17%, p < 0.001), resolution of insulin sensitivity (HOMA2-IR = - 23.4%, p = 0.002; Adipo IR = - 16%, p = 0.009) and inflammation [log resistin = - 6%, p = 0.07] were observed 3 months post-surgery. CEC significantly improved 3 months after surgery [Pre: 0.91 ± 0.13; Post: 1.02 ± 0.16; p = 0.001] despite a decrease in HDL-C levels. The change in CEC correlated with the change in apo A-I (r = 0.39, p = 0.02) and adiponectin levels (r = 0.35, p = 0.03). CONCLUSION: The results suggest that improvements in CEC, through improvement in adipose tissue health in terms of adipokine secretion and insulin sensitivity could be an important pathway in modulating obesity-related CVD risk.

Amino Acid-Functionalized Metal-Organic Frameworks for Asymmetric Base-Metal Catalysis.

We report a strategy to develop heterogeneous single-site enantioselective catalysts based on naturally occurring amino acids and earth-abundant metals for eco-friendly asymmetric catalysis. The grafting of amino acids within the pores of a metal-organic framework (MOF), followed by post-synthetic metalation with iron precursor, affords highly active and enantioselective (>99 % ee for 10 examples) catalysts for hydrosilylation and hydroboration of carbonyl compounds. Impressively, the MOF-Fe catalyst displayed high turnover numbers of up to 10 000 and was recycled and reused more than 15 times without diminishing the enantioselectivity. MOF-Fe displayed much higher activity and enantioselectivity than its homogeneous control catalyst, likely due to the formation of robust single-site catalyst in the MOF through site-isolation.

Serum Adipocytokines Levels and Their Association with Insulin Sensitivity in Morbidly Obese Individuals Undergoing Bariatric Surgery.

BACKGROUND: Obese adipose tissue secretes a variety of adipocytokines that act as metabolic regulators with complex mechanisms. Our objective was to compare serum concentration of a panel of adipocytokines between obese and non-obese individuals and identify any distinct patterns correlating with insulin sensitivity in obesity. METHODS: We designed a cross-sectional study among obese (body mass index [BMI] ≥30 kg/m2, n=62) and non-obese (BMI <25 kg/m2, n=32) individuals to compare circulating levels of the adipokines, such as adiponectin and resistin in conjunction with the measurement of the levels of inflammatory cytokines including C-reactive protein (CRP), interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α using Luminex multiplex immunoassay with drop array technology. Correlations between circulating adipocytokine levels and those of multiple well-established markers of insulin resistance including homeostatic model assessment of insulin resistance (HOMA-IR), homeostatic model assessment of ß-cell function (HOMA-ß) and quantitative insulin sensitivity check index were also established. RESULTS: CRP, IL-8, MCP-1, and TNF-α levels were higher in obese than non-obese individuals; the CRP and IL-8 differences were statistically significant. CRP correlated significantly with markers of insulin resistance (fasting plasma insulin, HOMA-IR, and QUICKI), and adiponectin correlated with HOMA-ß in obese individuals. We divided the group of obese individuals on the basis of HOMA-IR levels into insulin-resistant (IR; HOMA-IR ≥2.5) and insulin-sensitive (IS; HOMA-IR <2.5) groups; and 43 out of 62 participants were IR despite comparable BMIs. An overall proinflammatory profile was compared between IR and IS obese, though the values were higher in IR obese but the difference was not significant. CONCLUSION: Obesity is associated with a general inflammatory milieu and a crosstalk between adipocytokines and insulin resistance is complex as well as multifactorial.

Single-Site Cobalt-Catalyst Ligated with Pyridylimine-Functionalized Metal-Organic Frameworks for Arene and Benzylic Borylation.

We report a highly active single-site heterogeneous cobalt-catalyst based on a porous and robust pyridylimine-functionalized metal-organic frameworks (pyrim-MOF) for chemoselective borylation of arene and benzylic C-H bonds. The pyrim-MOF having UiO-68 topology, constructed from zirconium-cluster secondary building units and pyridylimine-functionalized dicarboxylate bridging linkers, was metalated with CoCl2 followed by treatment of NaEt3BH to give the cobalt-functionalized MOF-catalyst (pyrim-MOF-Co). Pyrim-MOF-Co has a broad substrate scope, allowing the C-H borylation of halogen-, alkoxy-, alkyl-substituted arenes as well as heterocyclic ring systems using B2pin2 or HBpin (pin = pinacolate) as the borylating agent to afford the corresponding arene- or alkyl-boronate esters in good yields. Pyrim-MOF-Co gave a turnover number (TON) of up to 2500 and could be recycled and reused at least 9 times. Pyrim-MOF-Co was also significantly more robust and active than its homogeneous control, highlighting the beneficial effect of active-site isolation within the MOF framework that prevents intermolecular decomposition. The experimental and computational studies suggested (pyrim•-)CoI(THF) as the active catalytic species within the MOF, which undergoes a mechanistic pathway of oxidative addition, turnover limiting σ-bond metathesis, followed by reductive elimination to afford the boronate ester.