Development of an IgG-Fc fusion COVID-19 subunit vaccine,AKS-452

AKS-452 is a biologically-engineered vaccine comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain antigen (Ag) and human IgG1 Fc (SP/RBD-Fc) in clinical development for the induction and augmentation of neutralizing IgG titers against SARS-CoV-2 viral infection to address the COVID-19 pandemic. The Fc moiety is designed to enhance immunogenicity by increasing uptake via Fc-receptors (FcγR) on Ag-presenting cells (APCs) and prolonging exposure due to neonatal Fc receptor (FcRn) recycling. AKS-452 induced approximately 20-fold greater neutralizing IgG titers in mice relative to those induced by SP/RBD without the Fc moiety and induced comparable long-term neutralizing titers with a single dose vs. two doses. To further enhance immunogenicity, AKS-452 was evaluated in formulations containing a panel of adjuvants in which the water-in-oil adjuvant, Montanide™ ISA 720, enhanced neutralizing IgG titers by approximately 7-fold after one and two doses in mice, including the neutralization of live SARS-CoV-2 virus infection of VERO-E6 cells. Furthermore, ISA 720-adjuvanted AKS-452 was immunogenic in rabbits and non-human primates (NHPs) and protected from infection and clinical symptoms with live SARS-CoV-2 virus in NHPs (USA-WA1/2020 viral strain) and the K18 human ACE2-trangenic (K18-huACE2-Tg) mouse (South African B.1.351 viral variant). These preclinical studies support the initiation of Phase I clinical studies with adjuvanted AKS-452 with the expectation that this room-temperature stable, Fc-fusion subunit vaccine can be rapidly and inexpensively manufactured to provide billions of doses per year especially in regions where the cold-chain is difficult to maintain.     

Steep Decrease of Gender Difference in DSM-IV Alcohol Use Disorder: A Comparison of Two Nation-wide Surveys Conducted 10 Years Apart in Korea

While decreasing trend in gender differences in alcohol use disorders was reported in Western countries, the change in Asian countries is unknown. This study aims to explore the shifts in gender difference in alcohol abuse (AA) and dependence (AD) in Korea. We compared the data from two nation-wide community surveys to evaluate gender differences in lifetime AA and AD by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Face-to-face interviews using the Composite International Diagnostic Interview (CIDI) were applied to all subjects in 2001 (n=6,220) and 2011 (n=6,022). Male-to-female ratio of odds was decreased from 6.41 (95% CI, 4.81-8.54) to 4.37 (95% CI, 3.35-5.71) for AA and from 3.75 (95% CI, 2.96-4.75) to 2.40 (95% CI, 1.80-3.19) for AD. Among those aged 18-29, gender gap even became statistically insignificant for AA (OR, 1.59; 95% CI, 0.97-2.63) and AD (OR, 1.18; 95% CI, 0.80-2.41) in 2011. Men generally showed decreased odds for AD (0.55; 95% CI, 0.45-0.67) and women aged 30-39 showed increased odds for AA (2.13; 95% CI 1.18-3.84) in 2011 compared to 2001. Decreased AD in men and increased AA in women seem to contribute to the decrease of gender gap. Increased risk for AA in young women suggests needs for interventions.     

Disparate exposure to physically demanding working conditions in France

BackgroundOur study was aimed at examining disparate exposure to physically demanding working conditions in France, a key objective being to identify the types of employees/jobs requiring high-priority preventive actions.MethodsWe analyzed the data from the 2017 French nationwide cross-sectional survey (SUMER) on occupational hazards to which French employees in various sectors were subjected. The prevalence of several types of physically demanding working conditions (lifting of heavy loads, awkward body postures, vibrations, noise, and extreme temperatures) was explored. Potential associations of individual and job characteristics with these factors of hardship at work were studied by multivariate logistic regression.ResultsIn total, 48% of employees were exposed to at least one physically demanding working condition and 24.8% were exposed to multiple constraints. While managers and intellectual professionals were exposed relatively infrequently to physical constraints, blue-collar workers experienced the highest frequency of exposure. On the one hand, the role of company size depended on the factor of hardship at work considered; on the other hand, employees in large-scale companies were generally less exposed. As expected, employees in the construction industry were the most exposed to physical constraints; that said, our results also show that some activities in the services sector (e.g., personal care, administrative and support services) were quite significantly affected by a wide array of physically demanding working conditions.ConclusionNotwithstanding the establishment in France of Plans de Santé au travail (preventive workplace health and safety plans), occupational risks were found to be high, and above all, they were unevenly distributed among the various socio-professional categories, and strongly contributed to social inequalities in health. Our results identify the types of publics to be designated as high-priority targets for preventive measures aimed at reducing the adverse impacts of physically demanding working conditions and the incidence of associated musculoskeletal disorders.     

Ocular changes in the mouse embryo following acute maternal ethanol intoxication

The development of the eye was investigated in the mouse embryo following a single administration of ethanol plus [3H]thymidine to the dam on day 13 of gestation. After 1 hr there was no difference in the number of labelled cells/100 micron 2 in the neural layer of the retina compared to controls, but there was an alcohol-related reduction in labelling density. After 24 hr there was an increase in the numbers of both pyknotic cells and mitotic figures, breaks occurred in the inner surface of the retina and cell debris was being extruded into the posterior chamber. At 48 hr the increase in pyknotic cells persisted, but there was less evidence of cell debris and the borders had been repaired. The estimated cell cycle time in the neural progenitor cells following maternal alcohol administration was increased 7-fold compared to controls. Morphometric analysis revealed that after 48 hr there were significant alcohol-related reductions in the width and depth of the eye, in the thickness of the neural layer and in the interocular distance. It appears that many of the ophthalmic abnormalities reported in human fetal alcohol syndrome can be produced in the mouse embryo following a single episode of acute maternal intoxication during a critical period of ocular ontogeny, and that they evolve primarily from disturbances in the normal patterns of recruitment and loss of neural progenitor cells in the developing retina.     

Enhancing Nurse Assessment of Alcohol and Drug Dependency: A Preliminary Study

The purpose of this project was to prepare nurses to provide brief interventions for clients with alcohol or other drug (AOD) dependency in order to reduce hospitalization, morbidity, and mortality. The project was a collaborative process between a major medical center and a school of nursing. Nurses were surveyed for understanding of alcohol and other drug assessment, and a day long training was provided to teach techniques of brief interventions. The short-term results included increased knowledge of nurses about AOD assessment. Long-term results indicated that 95% of patients referred to the AOD team were confirmed to have AOD problems (Dunn & Ries, 1997). This project documents the need for nurses to have more knowledge about AOD problems and brief intervention techniques.