Implementation and Application of Large-Scale Drug Virtual Screening

The molecular docking-based virtual screening technique evaluates the binding abilities between multiple ligand compounds and receptors to screen for the active compounds. In the context of the global spread of the COVID-19 pandemic, large-scale and rapid drug virtual screening is crucial for identifying potential drug molecules from massive datasets of ligand structures. The powerful computing power of supercomputer provides hardware guarantee for drug virtual screening, but the super large-scale drug virtual screening still faces many challenges that affects the effective execution of the calculation. Based on the analysis of the challenges, this paper proposes a centralized task distribution scheme with a central database, and designs a multi-level task distribution framework. The challenges are effectively solved through multi-level intelligent scheduling, multi-level compression processing of massive small molecule files, dynamic load balancing and high error tolerance management technology. An easy-touse"tree”multi-level task distribution system is implemented. A fast, efficient and stable drug virtual screening task distribution, calculation and result analysis function is realized, and the computing efficiency is nearly linear. Then, heterogeneous computing technology is used to complete the drug virtual screening of more than 2 billion compounds, for two different active sites for COVID-19, on the domestic super computing system, which provides a powerful computing guarantee for the super large-scale rapid virtual screening of explosive malignant infectious diseases. © 2023, Journal of Computer Engineering and Applications Beijing Co., Ltd.;Science Press. All rights reserved.

Diagnosing gestational diabetes during the Covid-19 pandemic using HbA1c rather than oral glucose tolerance test (OGTT)

The Royal College of Obstetrics and Gynaecology advocated replacing OGTT with HbA1c for gestational diabetes (GDM) screening for women with risk factors during the Covid-19 pandemic. HbA1c >=48mmol/mol/random plasma glucose (RPG) >=11.1mmol/l at booking indicated diabetes, and 41-47mmol/ mol/9-11mmol/ l prediabetes or possible GDM. Testing was repeated at 26 weeks if normal previously, with HbA1c >=39mmol/mol, fasting PG >=5.6mmol/l, or RPG >=9mmol/l diagnostic for GDM. A) At her clinic booking visit at 10 weeks gestation, 36 year-old South Asian female had HbA1c 55mmol/mol/RPG 9.5mmol/l suggesting undiagnosed type 2 diabetes. Initially managed with dietary advice and home blood glucose monitoring, metformin was added when self-monitored glucose above pregnancy targets (fasting and pre-meal <5.3mmol/l or 1 h post meal <7.8mmol/l) but insulin was required later. Metformin and insulin were stopped after delivery at 38 weeks with HbA1c 50mmol/mol three months postpartum, supporting the earlier diagnosis of type 2 diabetes. B) 32 year-old White Caucasian female was screened for GDM on booking at 11 weeks as BMI 38 kg/m2. HbA1c 44mmol/mol and RPG 6.9mmol/l confirmed GDM which was managed by dietary/lifestyle changes with glucose and pregnancy targets achieved until 28 weeks when metformin added. Normal delivery at 40 weeks with HbA1c 40mmol/mol three months postpartum triggered advice on long-term dietary/lifestyle changes and annual HbA1c checks. HbA1c was useful during the pandemic but most centres reverted to OGTT for GDM screening due to a significant fall in diagnoses using HbA1c >=39mmol/mol at 26 weeks. But, HbA1c testing was advantageous at booking to diagnose type 2 diabetes earlier.

Experiences of adult epilepsy patients with COVID-19 infections and vaccinations

Objective: To assess the course of COVID-19 infections and the tolerability of the mRNA vaccines of Moderna and Pfizer/BioNTech and the viral vector vaccines from Astra Zeneca and Johnson & Johnson in adult patients with epilepsy (PWE). Method(s): From July 2020 to July 2021, we consecutively included adult outpatients with confirmed epilepsy. These PWE were interviewed about COVID-19 infections and vaccinations. Results of follow-up visits were added until the cut-off date (December 31, 2021). The data of COVID-19-infected without vaccinations or fully vaccinated PWE without COVID-19 infections were analyzed. Full vaccination was defined as a double vaccination with the Pfizer/BionTech, Moderna, or Astra Zeneca vaccines or a single Johnson & Johnson vaccination. Result(s): At cut-off, 612 of 1152 PWE fulfilled the inclusion criteria: 51 PWE had been infected without vaccination and 561 had full vaccination without infection. Among the infected PWE, 76.5% presented with symptoms;9.8% had a severe course (one death). The leading symptoms were influenza-like disorders (48.7% of infected PWE with symptoms), anosmia (28.2%), and ageusia (20.5%). Seizure increases or relapses after sustained seizure freedom occurred in 7.8%. Adverse events (AEs) were reported by 113 vaccinated PWE (20.1% of all vaccinated PWE). The leading AEs were fatigue, fever, and headache. The AE rate per vaccine was 14.0% for Pfizer/BionTech, 32.7% for Moderna, 25.8% for Astra Zeneca, and 46.2% for Johnson & Johnson. Of the AEs, 93.3% lasted <=1 week. Seizure increase or relapse occurred in 1.4% and was significantly less frequent than in the infected group (p= 0.0016). Conclusion(s): The course of COVID-19 infections and the tolerability of the vaccines were similar as in the general population, yet, seizure worsening occurred more often after the infection than after the vaccination.Copyright © 2023, The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, part of Springer Nature.

FACTORS ASSOCIATED WITH ADHERENCE TO ANTI TNF-Α THERAPY DURING THE COVID-19 PANDEMIC IN PATIENTS WITH RHEUMATOID ARTHRITIS

BackgroundRheumatoid Arthritis (RA) patients are effectively treated with anti-TNF-α therapy. However, pharmacological non-adherence limits the achievement of the therapeutic objective. This is a multifactorial behavior where factors such as the route of administration, frequency, tolerance, perception of improvement, polypharmacy and social factors are involved [1,2].ObjectivesTo explore the factors associated with non-adherence to anti TNF-α in RA patients during the COVID-19 pandemic.MethodsThis is a cohort of RA patients treated with anti TNF-α in Medicarte SAS, a Colombian center for Immune-Mediated Diseases, between January to December 2021. The program implements strategies such as pharmacotherapeutic support, informed dispensing, phone calls, text messages and home care services to increase adherence. Adherence was defined as dispensing at least 10/12 (>0.80) prescribed monthly doses for 1 year. Sociodemographic characteristics, time in the program, DAS28-CRP, HAQ and treatment were included as exposure variables. For continuous variables, median and interquartile range (IQR) were calculated. Adjusted Odds Ratio (AOR) with logistic regression were calculated, and a p-value <0.05 was considered as statistically significant.Results565 patients were included, 85.8% (n=485) were women, median age 56 years (IQR: 49-65), disease evolution time 13.7 years (IQR: 7.7-20.8), 51% (n=288) had been in the program for more than 3 years, the median time in treatment with anti TNF-α was 3 years (IQR: 1-3) and DAS-28-CRP 2.4 (IQR: 1.6-3.4). The most frequently anti TNF-α prescribed was etanercept 46.0% (n=260), followed by adalimumab 23% (n=130), subcutaneous golimumab 13.3% (n=75), certolizumab 11.0% (n=62) and intravenous golimumab 6.7% (n=38). At the admission, 18.2% (n=103) of the patients had high activity, 38.6% (n=218) mild activity, 9.2% (n=52) low activity and 34% (n=192) were in remission. At the end of follow-up, 6.4% (n=36) of patients had high activity, 18.2% (n=103) mild activity, 14.3% (n= 81) low activity and 61.1% (n= 345) were in remission. The 51.5% (n=291) did not have pharmacological adherence. The use of etanercept (AOR 0.36 CI95% 0.23- 0.58, p < 0.001) and adequate functionality measured through HAQ (AOR 0.64 CI95% 0.42- 0.97, p < 0.04) were associated with a lower risk of non-adherence. Higher DAS28-CRP at the end of follow up was associated with non-adherence (AOR 1.29 CI95% 1.12 - 1.48, p < 0.001).ConclusionDuring COVID-19 pandemic, the implementation of strategies in the home care patient program guaranteed adherence close to 50% in our cohort. Higher values of DAS28-CRP were associated with non-adherence, whilst etanercept use and a normal HAQ value were associated with a higher probability of adherence.References[1]Marengo MF, Suarez-Almazor ME. Improving treatment adherence in patients with rheumatoid arthritis: what are the options? Int J Clin Rheumtol. 2015 Oct 1;10(5):345-356.[2]Smolen JS, Gladman D, McNeil HP, Mease PJ, Sieper J, Hojnik M, et al. Predicting adherence to therapy in rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis: a large cross-sectional study. RMD Open. 2019 Jan 11;5(1):e000585.Acknowledgements:NIL.Disclosure of InterestsWilmer Gerardo Rojas Zuleta Speakers bureau: Pfizer, Jannsen Cilag, Bristol Myers Squibb, Amgen, Eli lilly, Mario Barbosa: None declared, Oscar Jair Felipe Díaz Speakers bureau: Pfizer, Jannsen Cilag, Bristol Myers Squibb, Amgen, Eli lilly, Adelis Enrique Pantoja Marquez: None declared, Jeixa Canizales: None declared, Carolina Becerra-Arias: None declared, Jorge Hernando Donado Gómez: None declared, Natalia Duque Zapata: None declared.

Cardiac manifestations of post-COVID syndrome in children and adolescents.

The aim of the research. To study the features of cardiovascular system disorders in post-covid syndrome (PCS) in children and adolescents after a mild form of coronavirus infection (COVID-19). Material and methods. From 260 children and adolescents after a mild form of COVID-19, a total of 30 patients aged 7-17 years with cardiac manifestations of PCS were selected. Therewith, 32 patients with an uncomplicated form of the disease were selected to form a comparison group. In 3 and 6 months after disease onset, a comprehensive examination of patients was performed with a questionnaire on the subjective scale for MFI-20 assessment asthenia (Multidimensional Fatigue Inventory-20), electrocardiography (ECG), echocardiography;daily monitoring of ECG and blood pressure. The biochemical blood test included assay of creatine phosphokinase-MB (CPK-MB), troponin I and lactate dehydrogenase (LDH). Results. The incidence of PCS with cardiac manifestations amounted to 11.5 %. After 3 months from the disease onset, complaints of pain and discomfort in the chest, palpitations, fatigue, and poor exercise tolerance persisted. Asthenic syndrome was diagnosed in 70 % of patients. The "general asthenia" indicator totalled14 [12;16] points (p<0.001) and was associated with the age of patients (r=+0.5;p<0.05). Arrhythmic syndrome and conduction disorders were detected in 67% of children. Labile arterial hypertension and hypotension occurred in 23 % of the adolescents. The increase in CPK-MB remained in 17% of the children, LDH - in 10%. In the sixth month after the onset of the disease, there were no significant differences in the results of the examination in the observation groups. However, a decrease in the level of resistance within 6 months was recorded in 43.3% of the schoolchildren with PCS (p<0.001). Conclusion. The data obtained indicate the need for early verification of cardiopathies in children with COVID-19, determination of a set of therapeutic and rehabilitation measures as well as ECG monitoring.Copyright © 2022, Krasnoyarsk State Medical University. All rights reserved.

RETROSPECTIVE STUDY OF VITAMIN D DEFICIENCY IN RHEUMATOLOGIC PATIENTS DURING THE COVID-19 PANDEMIC IN POLAND

BackgroundBefore the COVID-19 pandemic it was estimated that nearly 70% of the population is deficient in vitamin D - 25(OH)D <20ng/ml in Poland [1]. The percentage was expected to increase due to indoor isolation during the COVID-19 pandemic. Vitamin D has a positive effect on the condition of the bones, affects the course of autoimmune diseases, the course of neurological diseases, in type 2 diabetes, vitamin D supplementation improves glucose tolerance and reduces insulin resistance [2,3,4].ObjectivesThe aim of the retrospective study was to determine what percentage of rheumatology clinic patients suffer from vitamin D deficiency and whether this condition is effectively treated.MethodsIn January 2023, a retrospective analysis of the documentation of 172 patients treated at the Rheumatology Outpatient Clinic in Bełżyce (Poland) in 2022 was conducted.ResultsResults: The mean age of the 172 patients whose documentation was analyzed was 60.43 years (min 19, max 88). There were 132 women (76.8%) and 40 men (23.2%) in this group. The mean concentration of vitamin D was 25.57ng/ml±SD11.9 (min 5.7, max 75, Me 22.8). Vitamin D deficiency was found in 44% (serum concentration <20mg/ml), suboptimal concentration (20-30ng/ml) in 31%, optimal concentration (30-50ng/ml) in 21%, and high concentration (>50ng/ml) ml) in 4%. All those with a deficit or deficiency (75 people) were prescribed cholecalciferol in a dose of 20,000 units orally, 1 capsule twice a week after breakfast for 2 months [5]. Patients with optimal vitamin D levels were advised to take a dose of 2,000 units per day. Among the patients with deficit or deficiency, 48 people came for a follow-up visit to check the level of vitamin D (64% of the group with too low vitamin D concentration;28% of the entire group whose documentation was analyzed). In the follow-up examination, the mean concentration of vitamin D was 37.14±9.8ng/ml (min 28, max 84, Me 35.3). Therefore, a statistically significant increase in the concentration of vitamin D in the blood was noted (p<0.05). In the group of people who came for the follow-up examination, there were 35 women, whose mean age was 60.7 years and 13 men (mean age 68.2 years).Conclusion:1. During the COVID-19 pandemic in the group of outpatient rheumatology patients, 75% had a deficiency or suboptimal level of vitamin D.2. Treatment with cholecalciferol in a dose of 20,000 IU twice a week orally for 2 months is effective treatment of vitamin D deficiency.3. Too low percentage of patients diagnosed with vitamin D deficiency come for visits and check-ups.References[1]Hilger J., Friedel A., Herr R.. A systematic review of vitamin D status in populations worldwide. Br J Nutr. 2013;9: 1023.[2]Karczmarewicz E., Czekuć-Kryskiewicz E., Płudowski P. Effect of vitamin D status on pharmacological treatment efficiency-impact on cost- effective management in medicine. Dermatoendocrinology, 2013;5: 299-304.[3]Zhu J., Bing C., Wilding J.P.H. Vitamin d receptor ligands attenuate the inflammatory profile of IL-1β-stimulated human white preadipocytes via modulating the NF-κB and unfolded protein response pathways Biochemical and Biophysical Research Communications 2-18, 503: 1049-1056.[4]Luan W., Hammond L.A. Vuillermot S. Maternal vitamin d prevents abnormal dopaminergic development and function in a mouse model of prenatal immune activation. Scientific Reports 2018;8 (1) article numer 9741.[5]Płudowski P., Karczmarewicz E. i wsp. Witamina D: Rekomendacje dawkowania w populacji osób zdrowych oraz w grupach ryzyka deficytów.Wytyczne dla Europy Środkowej 2013 r. Standardy Medyczne/Pediatria 2013, 10, 573-578 (in Polish).Acknowledgements:NIL.Disclosure of InterestsNone Declared.

GDM diagnosis criteria: Standard and Covid-19 criteria

Aim: Standard diagnosis of gestational diabetes (GDM) is based on the Oral Glucose Tolerance test (OGTT). During the Covid-19 outbreak, due to Covid restrictions, criteria were modified i.e Fasting Blood Glucose >=5.3 and/ or HbA1c >= 39 for diagnosis of GDM. After the lifting of the Covid restrictions, the standard criteria were reimplemented and on analyzing the data, it was highlighted that some of the patients could have tested negative for GDM based on Covid Criteria. Method(s): We analyzed the data of 43 patients based on standard criteria (OGTT and HbA1c) after Covid restrictions, with the following results. Result(s): 11/43(28%) patients who were diagnosed on the basis of standard criteria could have been missed based on Covid criteria. Out of 11 deliveries, 2 babies with weight above 4 kg. There were no admissions to NICU. One patient had postpartum hemorrhage with 670 mL of blood loss. Conclusion(s): This was a retrospective study in which we analyzed the data of 45 pregnant females diagnosed with GDM based on testing using the Covid criteria and compared this to 43 pregnant females who were diagnosed with GDM on the basis of OGTT based on GOLD standard NICE criteria. In addition, we also examined maternal and obstetric outcomes in both groups such as the mode of delivery, the baby's birth weight, the incidence of shoulder dystocia, mean blood loss (MBL), and NICU admission. We understand that Covid GDM diagnosis was a necessity of time. In this study, we want to learn what could have been missed with that diagnostic criteria. For future pandemics, we need to revise our diagnostic criteria to avoid the risk of underdiagnosing GDM and associated complications.

Teaching a tolerance for ambiguity as a response to crisis learning contexts

Using insights from the changes made to a workshop developed before, but occurring after the pandemic, I describe the usefulness of design thinking activities and approaches to education in the post-COVID teaching era. I argue that design thinking techniques help build awareness around tolerance for ambiguity as an opportunity to inspire creative teaching solutions. This transferable skill is important for our students as soon-to-be graduates, and for faculty looking to build resilience in this uncertain time. Using Boyer's framework for scholarship, I explore opportunities to connect the teaching and learning goals of students and faculty. © Springer Nature Switzerland AG 2021. All rights reserved.

Optimal continuous glucose monitoring metrics for identification of women with gestational diabetes

Aims: Continuous glucose monitoring (CGM) is widely used in pregnant women with pre-gestational diabetes, but optimal targets have not been defined in gestational diabetes. Previous work identified mild hyperglycaemia in pregnant women without gestational diabetes, but with risk factors such as obesity. We aimed to examine CGM metrics and patterns of glycaemia in women with gestational diabetes compared to healthy pregnant women with comparable risk factors. Method(s): We recruited 73 healthy women with >1 risk factor (gestational diabetes excluded using Covid-19 criteria, OGTT) and 200 women with gestational diabetes (NICE and interim-Covid- 19 criteria) from antenatal clinics at 28 weeks' gestation. A Dexcom G6 CGM device was cited on the non-dominant upper arm. Result(s): Women with gestational diabetes had significantly higher weight (mean +/- SEM 95.7 kg +/- 1.3 Vs 85.4 kg +/- 2.2) and BMI (36.0 +/- 0.5 Vs 31.3 +/- 0.7) compared to healthy pregnant women (p < 0.01). Women with gestational diabetes had significantly higher mean CGM-glucose (mean +/- SEM 5.6 +/- 0.01 Vs 5.4 +/- 0.01mmol/l;p < 0.01), significantly altered time-below- range (median(IQR);1.0% (0.2-2.9) vs 2.5% (0.7-5.5);p < 0.05) and time-in- range (95.0% (91.1-97.9) vs 94.5% (87.9-96.2);p < 0.05) but comparable time-above- range to healthy women with risk factors. Diurnal glucose profiles in women with gestational diabetes were comparable to healthy women between 14:00 and 18:00, but demonstrated significant increases in glucose at all other time points during the 24-h cycle (p < 0.01). Conclusion(s): Mean CGM glucose is the most reliable CGM metric to distinguish women with gestational diabetes from healthy pregnant women with risk factors.

Was the diagnosis of gestational diabetes from 34 weeks gestation of pregnancy more prevalent during Covid-19 due to the change in how gestational diabetes was diagnosed?

Aim: During Covid we noticed that more women were being diagnosed with Gestational Diabetes (GDM) from 34 weeks gestation than prior to Covid. It was suspected that this was due to how GDM was diagnosed, from Oral Glucose Tolerance Test (OGTT) prior to Covid to HbA1c with Fasting or Random Blood Glucose (RBG) during Covid. Method(s): An audit of our GDM database was performed, looking at rates of late GDM diagnosis from 2018-present. Result(s): Prior to Covid the late diagnosis rate was 14-15%. In 2020 and 2021 this increased to 27.7%. This year diagnosis is only by OGTT, and the rate has dropped to 21%. There was also a significant rise in the number of women who were being diagnosed from 34 weeks gestation whom had previously been tested for GDM earlier in their pregnancy. In 2018 and 2019 52-56% of these women had previously been tested. In 2020 this increased up to 84% and fell to 74% in 2021. This year the rate has fallen to 67%. In 2018 and 2019 all women had been diagnosed using OGTT's. In 2020 61% of women had previously been tested for GDM by HbA1c and RBG, with this increasing to 84% in 2021. This year only 10% had previously been tested using HbA1 and RBG. Conclusion(s): The sharp increase in late diagnosis of GDM during the Covid seems to be related to the change in diagnostic testing and shows that OGTT is the more accurate way to diagnose GDM and not HbA1c with RBG.

Efficacy and safety of bovhyaluronidase azoximer (Longidase) in patients with post-COVID syndrome: results of an open, prospective, controlled, comparative, multicenter clinical trial DISSOLVE.

Post-COVID syndrome develops after COVID-19 (COronaVIrus Disease 2019) and leads to cumulative effects in the form of shortness of breath and impaired lung function. Notably, patients with airway inflammation and COVID-19 were found to have increased concentrations of hyaluronic acid (HA). Since bovhyaluronidase azoximer (Longidase) catalyzes the hydrolysis of HA, this drug has the potential to reduce HA levels and improve lung function in patients with post-COVID syndrome. The aim of the DISSOLVE trial, which was conducted early in the pandemic, was to investigate the efficacy and safety of bovhyaluronidase azoximer in patients with symptoms associated with post-COVID syndrome. Methods. An open, prospective, controlled, comparative, multicenter clinical trial (NCT04645368) included adult patients (n = 160) who had post-COVID syndrome. Patients in the treatment group (n = 81) received bovhyaluronidase azoximer, and individuals in the control group (n = 79) were followed up without intervention. The study included physical examination, evaluation of forced vital capacity (FVC), assessment of dyspnea with the Modified Medical Research Council Dyspnea Scale (mMRC), 6-minute walking test, and pulse oximetry. These indicators were measured on 3 visits, at days 1 (baseline), 75, and 180. In addition, the number of patients who experienced adverse events and serious adverse events were recorded. Results. Baseline patient characteristics in the treatment group and the control group were similar. In the treatment group, there was a statistically significant reduction in residual pulmonary abnormalities after visit 2 (day 75) and visit 3 (day 180). In addition, FVC, pulse oximetry values, and functional exercise tolerance increased statistically significantly at days 75 and 180 compared to baseline. The mMRC scores for dyspnea decreased statistically significantly in the treatment group over 75 days. The safety profile of the drug was reported to be favorable throughout the study. Conclusion. Treatment with bovhyaluronidase azoximer in patients with post-COVID syndrome showed improvement in FVC, pulse oximetry, functional exercise tolerance, and mMRC dyspnea.Copyright © Chuchalin A.G. et al., 2023.

COVID-19 among Hospitalized Patients with Diabetes in Karachi: A Single Centre Study

Aim: To evaluate the clinical characteristics, severity, and outcomes of local COVID-19 patients with diabetes. Study Design: Case series Place and duration of study: Orthopedic Medical Institute Hospital, Karachi from 1st September 2020 to 28th February 2021. Method(s): One hundred and forty seven COVID-19 positive patients with diabetes and pre-diabetes were enrolled. The patients' demographic and clinical information specific to COVID-19 and diabetes was collected and analyzed. Result(s): The mean age of 64.03+/-11.56 years. The ischemic heart disease (39.9%) and hypertension (74.3%) were the two most prevalent comorbid conditions. The overall mortality rate of 20.3%. Between patients with diabetes receiving steroids and those receiving no steroids, the mean fasting (FBG) and random blood glucose (RBG) were relatively elevated. Glycemic control had no discernible impact on the severity, results, or length of the COVID-19 hospital stay (p>0.05). Conclusion(s): No significant effect of diabetes millitus control on COVID severity and outcomes, but the altered blood glucose levels suggest a need to define specific targeted intervention for COVID-19 patients with comorbidities, specifically diabetes mellitus.Copyright © 2023 Lahore Medical And Dental College. All rights reserved.

IgG4 Antibodies Induced by Repeated Vaccination May Generate Immune Tolerance to the SARS-CoV-2 Spike Protein.

Less than a year after the global emergence of the coronavirus SARS-CoV-2, a novel vaccine platform based on mRNA technology was introduced to the market. Globally, around 13.38 billion COVID-19 vaccine doses of diverse platforms have been administered. To date, 72.3% of the total population has been injected at least once with a COVID-19 vaccine. As the immunity provided by these vaccines rapidly wanes, their ability to prevent hospitalization and severe disease in individuals with comorbidities has recently been questioned, and increasing evidence has shown that, as with many other vaccines, they do not produce sterilizing immunity, allowing people to suffer frequent re-infections. Additionally, recent investigations have found abnormally high levels of IgG4 in people who were administered two or more injections of the mRNA vaccines. HIV, Malaria, and Pertussis vaccines have also been reported to induce higher-than-normal IgG4 synthesis. Overall, there are three critical factors determining the class switch to IgG4 antibodies: excessive antigen concentration, repeated vaccination, and the type of vaccine used. It has been suggested that an increase in IgG4 levels could have a protecting role by preventing immune over-activation, similar to that occurring during successful allergen-specific immunotherapy by inhibiting IgE-induced effects. However, emerging evidence suggests that the reported increase in IgG4 levels detected after repeated vaccination with the mRNA vaccines may not be a protective mechanism; rather, it constitutes an immune tolerance mechanism to the spike protein that could promote unopposed SARS-CoV2 infection and replication by suppressing natural antiviral responses. Increased IgG4 synthesis due to repeated mRNA vaccination with high antigen concentrations may also cause autoimmune diseases, and promote cancer growth and autoimmune myocarditis in susceptible individuals.

Influence of Sensation Seeking and Life Satisfaction Expectancy on Stock Addiction Tendency: Moderating Effect of Distress Tolerance.

Due to the COVID-19 pandemic, a very low interest rate policy was economically applied in Korea, and various investment activities through loans were activated. Real estate and stock prices rose rapidly, and many people became involved in stock investments because of economic instability. However, hastily started investment behavior resulted in economic loss and addictive behavior in stocks. The phenomenon of using stock investment to satisfy individual sensation seeking or addictive dependence on stocks due to lowered life satisfaction expectancy can become a serious social problem. However, the improvement of distress tolerance and the ability to endure pain despite frequent stock price fluctuations or lowered life satisfaction expectancy would be good alternatives to prevent stock addiction tendency. Therefore, the purpose of this study is to test the moderating effect of distress tolerance on the effect of adults' sensation seeking and life satisfaction expectancy in stock addiction tendencies. The participants were 272 adults with stock investment experience. As a result, distress tolerance significantly moderated the positive effect of sensation seeking on stock addiction tendency. In addition, life satisfaction expectancy did not significantly increase in the group with high distress tolerance even if life satisfaction expectancy was lowered. These results suggest that stock addiction can be prevented by enhancing distress tolerance.

Prevalence of Hyperglycemia in Pregnancy and Related Screening Practices in Rural Dehradun: The First Population-Based Study from Uttarakhand (PGDRD-1).

Aims: Phase I of the Prevalence of Gestational Diabetes Mellitus in Rural Dehradun (PGDRD) project estimates hyperglycemia in pregnancy (HIP) prevalence and identifies gaps in the utilization of community-related services in rural areas of the Dehradun district (western Uttarakhand); a state where notably no prior population-based study has ever been conducted despite being an Empowered Action Group state for more than two decades. Methods: Using a multistage random sampling technique, 1,223 pregnant women locally registered in the rural field practice area of a block were identified. Those requiring HIP screening were subjected to a 2-h 75 g oral glucose tolerance test during the house visit irrespective of their period-of-gestation and last meal timings, diagnosed using the Diabetes in Pregnancy Study Group India (DIPSI) criterion (when indicated). Data were collected by personal interviews using a pretested data collection tool. Statistical Package for Social Sciences version 20.0 was used for analysis. Results: The overall HIP prevalence recorded was 9.7% (95% CI: 8.1-11.5%); the majority (95.8%) were GDM followed by overt DIP (4.2%). Less than 1% of the subjects (0.7%) self-reported pre-GDM. Despite this burden, more than three-fourths were never screened for HIP in their pregnancy. Of those tested, the majority availed secondary healthcare facilities. Few even had to bear expenses in private with a very handful being tested free-of-cost by ANM in the community; findings that altogether sharply contrast to those recommended by national protocols. Conclusion: Despite the high HIP burden, beneficiaries are unable to utilize community-related universal screening protocols as desired.

CD71+ erythroid cells suppress T-cell effector functions and predict immunotherapy outcomes in patients with virus-associated solid tumors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer. However, only a portion of patients respond to such treatments. Therefore, it remains a prevailing clinical need to identify factors associated with acquired resistance or lack of response to ICIs. We hypothesized that the immunosuppressive CD71+ erythroid cells (CECs) within the tumor and/or distant 'out-of-field' may impair antitumor response. METHODS: We studied 38 patients with cancer through a phase II clinical trial investigating the effects of oral valproate combined with avelumab (anti-programmed death-ligand 1 (PD-L1)) in virus-associated solid tumors (VASTs). We quantified the frequency/functionality of CECs in blood and biopsies of patients. Also, we established an animal model of melanoma (B16-F10) to investigate the possible effects of erythropoietin (EPO) treatment on anti-PD-L1 therapy. RESULTS: We found a substantial expansion of CECs in the blood of patients with VAST compared with healthy controls. We noted that the frequency of CECs in circulation was significantly higher at the baseline and throughout the study in non-responders versus responders to PD-L1 therapy. Moreover, we observed that CECs in a dose-dependent manner suppress effector functions of autologous T cells in vitro. The subpopulation of CD45+CECs appears to have a more robust immunosuppressive property compared with their CD45- counterparts. This was illustrated by a stronger expression of reactive oxygen species, PD-L1/PD-L2, and V-domain Ig suppressor of T-cell activation in this subpopulation. Lastly, we found a higher frequency of CECs in the blood circulation at the later cancer stage and their abundance was associated with anemia, and a poor response to immunotherapy. Finally, we report the expansion of CECs in the spleen and tumor microenvironment of mice with melanoma. We found that although CECs in tumor-bearing mice secret artemin, this was not the case for VAST-derived CECs in humans. Notably, our results imply that EPO, a frequently used drug for anemia treatment in patients with cancer, may promote the generation of CECs and subsequently abrogates the therapeutic effects of ICIs (eg, anti-PD-L1). CONCLUSIONS: Our results demonstrate that anemia by the expansion of CECs may enhance cancer progression. Notably, measuring the frequency of CECs may serve as a valuable biomarker to predict immunotherapy outcomes.

Revisiting the policy implications of COVID-19, asylum seekers, and migrants on the Mexico–U.S. border: Creating (and maintaining) states of exception in the Trump and Biden administrations

Public policy choices continue to bring dramatic changes to migration practices in the era of the coronavirus in the United States. In this article, we argue that the COVID-19 pandemic facilitated the creation and maintenance of states of exception while continuing to destabilize practices at the Mexico–U.S. border through the politics of fear. Specifically, the Migrant Protection Protocols (MPP), Zero Tolerance Policy (ZTP), COVID-19 CAPIO, Asylum Cooperative Agreements (ACA), and Title 42 used an arcane section of U.S. law to immediately expel asylum seekers and refugees. We show that these policies highlight the formation and maintenance of states of exception consistent with the work of Agamben. We further discuss how the politics of fear can reinforce hegemonic narratives targeting asylum seekers while shaping political agendas that lean toward a specific brand of nationalism using public health as a context. The U.S. government under the Trump administration—and the Biden administration to a lesser, yet continuous, extent—constructed these policies aimed primarily at refugees and asylum seekers from El Salvador, Guatemala, Honduras, and Mexico thereby violating laws and international treaty obligations. Related Articles: Duman, Yoav H. 2014. "Reducing the Fog? Immigrant Regularization and the State.” Politics & Policy 42(2): 187–220. https://doi.org/10.1111/polp.12065. Garrett, Terence Michael. 2020. "The Security Apparatus, Federal Magistrate Courts, and Detention Centers as Simulacra: The Effects of Trump's Zero Tolerance Policy on Migrants and Refugees in the Rio Grande Valley.” Politics & Policy 48(2): 372–95. https://doi.org/10.1111/polp.12348. Maggio, James. 2007. "The Presidential Rhetoric of Terror: The (Re)Creation of Reality Immediately after 9/11.” Politics & Policy 35(4): 819–35. https://doi.org/10.1111/j.1747-1346.2007.00085.x. © 2023 Policy Studies Organization.

Residents' attitudes, perceptions and the development of positive tourism behaviours amid COVID -19

Local people's pro-tourism behavioural intention plays an important role in determining the sustainability and success of a tourism destination. A semi-structured questionnaire was randomly administered to residents aged 18 years and above of Botswana's two premier tourism centres (Maun and Kasane). These two exotic tourism areas were chosen in this study to ensure enrichment of the literature through sharing of lived experiences and critical decision-making by people in the face of an impending disaster (i.e. COVID-19) threatening their existence. The Theory of Reasoned Action (TRA) was used to provide a better understanding in linking residents' attitudes in supporting or opposing tourism development in the face of COVID-19. Overall, majority (67.5%, p = 0.015) of the respondents indicated that they are willing to accept some inconvenience as long as they benefit from tourism industry. Also, most (84.4% (p = 0.034)) residents indicated that they were willing to welcome tourists because of the contribution tourists bring to the economy of their area. Thus, a positive attitude towards tourism development and tourists from locals will likely lead to a more positive behaviour supporting tourism in host communities. The study recommends that, of utmost importance, key stakeholders in the tourism industry including policymakers and planners should devise and implement strategies geared towards positively influencing attitudes of local communities towards tourism development. The results from this study will assist government and other tourism stakeholders as they devise mitigating strategies to sustain and guide future tourism operations following socioeconomic devastations from COVID-19 pandemic.

Addressing mental health, misinformation, & religious tensions among South Asian students across California higher education during the COVID-19 pandemic: A qualitative research study.

Background: South Asian Americans comprise one of the fastest-growing ethnic groups in the US. Nevertheless, the scientific literature on the experiences of South Asian students is lacking, where often studies focused on Asian Americans exclude South Asians altogether. South Asian students have unique experiences in California higher education, often having to cope with high pressure to perform academically and various social responsibilities associated with being first-, second-, or third-generation American.Many South Asian countries have been more severely affected by COVID-19 due to the density of people living in close proximity to one another. Students of South Asian origin worry for their families overseas, especially as the COVID-19 pandemic has impacted populations there to a more considerable extent. Methodology: This was a qualitative research study conducted using in-depth interviews with 25 students who identified as South Asian and were currently enrolled in higher education in California at the time they were interviewed. Ads were placed on social media networks, such as Facebook and Twitter, and participation in the study was voluntary. Students were chosen randomly to avoid bias. Study participants described their experiences navigating higher education throughout the ongoing COVID-19 pandemic in relation to their social, economic, cultural, and political spheres. Interviews were mainly conducted through Zoom, some through emails or phone calls. All participants will remain anonymous to protect the identities of students.This project sought to understand the experiences of South Asian students as they navigate the new normal amidst a global crisis. Qualitative responses were indexed by themes, with South Asian students reporting a relationship between the pandemic and worsened academic experiences, issues of exacerbated mental health, the spread of misinformation, and increased religious tensions.This research reflects pragmatism, and the findings of this paper are coupled with suggested recommendations to ameliorate pandemic related issues for future South Asian students. The project was conducted through both inductive and qualitative approaches. The research strategy is action research, and the research was meant to shine a light on issues South Asian students face and help university administrations understand how to better support students during a pandemic. The time horizon is cross-sectional. The research focuses on COVID-19 in relation to South Asian students' performance and health.At 25 participants, data saturation was reached. Further participants were not needed as the qualitative research data was sufficient to draw conclusions from. The research was deemed to pose no risk to students; therefore, approval from an ethical committee was not sought. All participants signed consent forms in order to participate.Follow-up interviews were conducted to address students' experiences with family in India experiencing the B.167.2 variant and the transition back to in-person learning following virtual schooling. Conclusions/significance: South Asian students in higher education bear a unique set of responsibilities in addition to the already rigorous coursework associated with college. However, the stresses and health of South Asian students often go understudied or overlooked. This research serves to begin to fill in the gaps in literature of South Asian experiences in higher education.The pandemic posed additional challenges for students, who lost access to their campus communities with university education going virtual, and many South Asian students had to move back home. Through this qualitative research study analyzing the experiences of South Asians enrolled in California higher education, it can be concluded that there is a relationship between the COVID-19 pandemic and students' academic performance, mental health, as well as an increase in the amount of misinformation spread regarding COVID-19 public safety guidelines.