Role of HLA polymorphism in COVID-19 progression in the Bulgarian population

The SARS-CoV-2 outbreak has impacted different socioeconomic aspects of our societies and represents a global health problem. The different rates of infection are heavily influenced by host genetic factors such as the variability in the HLA region. The aim of our study was to evaluate the role of specific HLA alleles in the Bulgarian population that contribute to COVID-19 progression. 76 Bulgarian patients (median age 59.4;range 25-84) with COVID-19, separated into 3 groups based on the severity of the infection, were included in the study. All patients were typed at allele level for HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1. Data from a representative Bulgarian population control group of young individuals (n = 540;median age 28,5;range 18-38) with unknown infectious status was used for comparison. Among the patient group, HLA-A*23:01 (OR = 3.16;p = 0.016), and DQB1*05:03 (OR = 3.1;p = 0.0009) showed positive association with moderate course of COVID-19, whereas DRB1*07:01 (OR = 2.54;p = 0.018) was associated with more severe disease. We found that A*01:01 (OR = 1.82;p = 0.018), B*35:03 (OR = 2.22;p = 0.011), B*40:06 (OR = 23.59;p = 0.0001), and DRB1*14:01 (OR = 3.37;p = 0.015) strongly correlate with the disease progression and could be considered as high-risk alleles. Furthermore, A*02:01 (OR = 0.4;p = 0.02), and DQB1*03:01 (OR = 0.47;p = 0.025) were predominantly found in asymptomatic patients and controls and probably exert a protective effect. Population-based and intra-individual variability of the HLA complex could partially explain the different courses of COVID-19. Despite some limitations, our preliminary data shows that some HLA alleles may be associated with a more severe course of the SARS-Cov infection, while others could possibly be considered protective. This work was supported by grant KP06DK1/13, 2021, Ministry of Education and Science, Bulgaria.

Improving Taxation of Small and Medium Enterprises in Russia

The paper focuses on some measures to improve the taxation of small- and medium-sized businesses. The legislation has many problems that should be solved in the field of taxation of business. The authors conclude that the discussed issue is problematic at the federal and regional levels because it is impossible to implement tasks and objectives for developing small and medium enterprises (including tax revenues) without state and regional support. The application of effective measures will increase the quantitative growth of entrepreneurs and the importance of their contribution to the regional and national economy. In scientific terms, a significant result is the application of a comprehensive and systemic method of the considered relationship with the use of the methodological tools of scientific research of the raised issues. The research confirms the need to further improve the practical activities of the subjects of commercial and entrepreneurial relations and their taxation, which is important in the current context of restrictions and the COVID-19 pandemics, which have considerably influenced the economic indicators of 2020–2021. The strategy for the development of small and medium entrepreneurship in the Russian Federation until 2030 clearly states that about 20% of the GRP in Russia and over one-third of GRP in some regions are created by small businesses. In a developed market economy, entrepreneurial activity is one of the fundamental segments of the market because it is one of the main indicators of economic growth. Consequently, the economy of Russia, like most developed countries in the world, is built on market principles directly regulated in the legislative acts of the national and international agreements. These principles include freedom of entrepreneurial activity, diversity of ownership, market pricing system, and limited government intervention in the entrepreneurial sphere. The country solves the issues considering all existing internal mechanisms. © 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Discovery: Transition of an Inquiry-focused Learning Program to a Virtual Platform During the COVID-19 Pandemic (Evaluation)

The shift to distance learning in response to the COVID-19 pandemic has presented teachers and students with several challenges. Teachers have found themselves quickly creating distance learning materials to provide equal or greater educational opportunity and engagement as in-person instruction. This shift is met with parallel increased demand on students to independently manage their learning and coursework with the absence of in-person supervision, support, and peer interaction. In this work, we describe our approach and observations in transitioning Discovery, a secondary student science, technology, engineering, and mathematics (STEM) education program, to a virtual platform. Developed by graduate students in 2016, Discovery was designed to engage secondary students in semester-long inquiry-based projects within the context of biomedical engineering. Projects are designed to foster and reinforce critical thinking skills required for post-secondary study. Throughout the semester, students design and execute experiments within post-secondary laboratories with instructional support from both their teachers and graduate student volunteers. In response to university teaching space closures in early 2020, we developed and delivered a virtual offering of Discovery. In contrast to in-person delivery, this initial virtual offering placed greater emphasis upon quantitative analysis rather than experimental design and execution. Access to virtual laboratory simulations was provided as a substitute for in-laboratory skill development. While overall assessment of student (survey instrument) and teacher (interviews) experiences revealed a highly positive perception of the program experience, areas for improvement were also highlighted. Many students reported struggling with motivation to keep up with course materials and soft deadlines (60%) as well as the lack of guidance provided by in-person mentor and teacher interactions (50%). Teacher interviews echoed quantified student perceptions, but further identified lamentation at the loss of student-driven, open-ended, and iterative problem-solving opportunities typically afforded by Discovery. Consequently, we developed an adjusted virtual program for the Fall 2020 term. The redesigned program reintroduced the open-ended aspect of previous in-person projects, and rather than including access to commercially available virtual laboratory simulation, greater focus was placed on design of experimental procedures that were evaluated and simulated by graduate students. Additionally, greater care was taken to discretize project components and deliverable deadlines to provide enhanced structure and guidance for students. We observed this updated program structure to similar outcomes of in-person offerings. A slight majority (51.4%) of Fall 2020 students achieved higher grades for Discovery deliverables than other class assessments. In post-program surveys, ~49% of students indicated they are more likely to pursue STEM courses, ~89% would participate in the program again, and ~78% responded that the experience made them more comfortable with completing university or college level laboratory work. While these results were encouraging, comparisons to previous in-person outcomes and analysis of teacher experiences (interviews) highlighted persistent gaps in student experience while completing the program virtually. © American Society for Engineering Education, 2021

The evolution of the education module for men with metastatic prostate cancer (mPC) in the prostate cancer supportive care (PCSC) program

Background: The PCSC Program was initiated in 2013 at the Vancouver Prostate Centre to provide a comprehensive program for patients and partners with prostate cancer. This program provides educational sessions (ES) and clinical services, including decision-making for primary therapy, sexual health, pelvic floor physiotherapy, hormone therapy, counseling, exercise, and nutrition for patients in BC, Canada. In 2016, the PCSC Program expanded to BC Cancer Victoria and in 2017 to other BC Cancer sites. In 2018, medical oncologists (MDS) in Victoria (JR, SP) developed an Education Module addressing treatment options for men with metastatic hormone sensitive (mHSPC) and metastatic castration resistant (mCRPC) disease. MDS delivered in-person ES in Victoria in 2018 and, in 2019, added a virtual platform (VP) option. From 3-5/2020, the ESs were on hold due to the COVID pandemic and parental leaves. In 6/2020, the ESs resumed only on VP, and the PCSC Oncology Nurse Practitioner (NP), NI, gave the presentations for the MDS on leave. In 10/2020, due to a changing standard of care for mHSPC, the PCSC team consolidated the two ESs into one. We report on the evolution of this Education Module in response to both the changing standard of care and the COVID pandemic. Methods: We prospectively collected attendance and patient characteristic metrics from all ES for men with mPC. We tracked presenter type (MD vs. NP) and prospectively collected anonymous patient satisfaction questionnaires. Results: From 1/2018 to 1/2021, 100 men registered for 27 ES;81 men, 41 partners, and 2 family members actually attended. 48/75 (64%) men were white, 39/75 (52%) retired, and 56/75 (74.7%) married. 47 men attended 12 mHSPC ES, 13 men attended ten mCRPC ES, and 17 attended four consolidated ES. MDS presented 15 ES, and the NP presented 12 ES. Responses to questions on 70 satisfaction surveys were similar for MD vs. NP presenters. 9 responders to the recently added VP-specific questions said they agreed (4) or strongly agreed (5) that it was beneficial to watch the ES at home on a computer. The Table below shows attendance per site per year. Conclusions: The ESs for men with mPC were well-received. Although there was a VP option before COVID, attendance increased significantly after the lockdown as patients and providers became more familiar with VPs. Satisfaction surveys confirmed that an NP could deliver the ES rather than MD. Consolidation of the mHSPC and mCRPC ES reflected the changing standard of care and resulted in more efficient use of presenter time. Virtual delivery of the sessions provided greater access to those living in distant or remote areas of the province and those in lockdown during the COVID pandemic.

Case study with chloroquine and hydroxychloroquine by using a thermal aerosolization process coupled to SUPER SESI-HRMS

Severe acute respiratory syndrome coronavirus 2 was identified in January 2020 as the cause of the SARS-like atypical pneumonia called coronavirus disease 2019. Recent publications have brought attention to the possible benefit of chloroquine (CQ) and its analog hydroxychloroquine (HCQ) in treatment of patients infected by this coronavirus. Previous research has demonstrated a narrow margin between the therapeutic and toxic doses of CQ and HCQ. In this study, we investigated the feasibility of developing inhalable forms of the antiviral drugs CQ and HCQ. The drugs were solubilized in an appropriate carrier and subjected to thermal aerosolization to generate an aerosol. The liquid formulation was evaporated by heating and subsequently cooled, which triggered nucleation and condensation processes that lead to aerosol formation. The aerosol was generated and assessed by using a programmable dual syringe pump coupled to the aerosol generation device, which guaranteed active drawing of a specified volume of air. The chemicals were detected by using secondary electrospray ionization interfaced with a Q Exactive mass spectrometer (MS). Transfer rate was assessed by analyzing the chemicals present in aerosol particles trapped in a Cambridge filter pad, by using liquid chromatography coupled to MS detection. Both CQ and HCQ solutions showed good potential for thermal aerosolization. These formulations are currently undergoing further improvements in parallel with transfer rate optimization related to thermal aerosol generation and gas/liquid phase partitioning. The developed methods and protocol for thermal drug aerosolization could have potential applications in treatment of infected people.