Hybridization Approach Toward Novel Antituberculars: Design, Synthesis, and Biological Evaluation of Compounds Combining Pyrazinamide and 4-Aminosalicylic Acid.

Apart from the SARS-CoV-2 virus, tuberculosis remains the leading cause of death from a single infectious agent according to the World Health Organization. As part of our long-term research, we prepared a series of hybrid compounds combining pyrazinamide, a first-line antitubercular agent, and 4-aminosalicylic acid (PAS), a second-line agent. Compound 11 was found to be the most potent, with a broad spectrum of antimycobacterial activity and selectivity toward mycobacterial strains over other pathogens. It also retained its in vitro activity against multiple-drug-resistant mycobacterial strains. Several structural modifications were attempted to improve the in vitro antimycobacterial activity. The δ-lactone form of compound 11 (11') had more potent in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv. Compound 11 was advanced for in vivo studies, where it was proved to be nontoxic in Galleria mellonella and zebrafish models, and it reduced the number of colony-forming units in spleens in the murine model of tuberculosis. Biochemical studies showed that compound 11 targets mycobacterial dihydrofolate reductases (DHFR). An in silico docking study combined with molecular dynamics identified a viable binding mode of compound 11 in mycobacterial DHFR. The lactone 11' opens in human plasma to its parent compound 11 (t1/2 = 21.4 min). Compound 11 was metabolized by human liver fraction by slow hydrolysis of the amidic bond (t1/2 = 187 min) to yield PAS and its starting 6-chloropyrazinoic acid. The long t1/2 of compound 11 overcomes the main drawback of PAS (short t1/2 necessitating frequent administration of high doses of PAS).

Secondary School Teachers and Outpatient Physicians: Differences in Attitudes towards Vaccination against COVID-19 in Slovakia.

The aim of this study was to evaluate the differences in attitudes towards vaccination against COVID-19 among secondary school teachers and outpatient physicians. A cross-sectional study was realised using anonymous questionnaires. The EPI Info 7 program and R software, version 4.0.2 were used for statistical analysis. The questionnaire was completed by 868 respondents (teaching staff N = 451; outpatient physician N = 417). The number of employees vaccinated against COVID-19 was 742 (85.5%). The number of those vaccinated against COVID-19 and influenza (last season) was 192 (21.9%). The statistically significant predictors were the level of fear of COVID-19 (OR 1.40; 95% CI 1.29-1.52), profession-outpatient physicians (OR 2.56; 95% CI 1.55-4.23), history of COVID-19 (OR 0.34; 95% CI 0.22-0.54), gender (OR 0.55; 95% CI 0.33-0.89) and influenza vaccination at any time in the past (OR 3.52; 95% CI 1.10-11.31). The strongest motivation for vaccination against COVID-19 among physicians was the prevention of the spread of COVID-19 during the performance of their profession (N = 336; 87%); among teachers, it was the protection of family members (N = 258; 73%). The most common reason for vaccine hesitancy was concern about vaccine safety (N = 80; 63.5%).

Prevalence of Burnout Syndrome in COVID-19 and Non-COVID-19 Units in University Hospital: A Cross-Sectional Study.

The aim of this study was to assess prevalence and associated risk factors of burnout syndrome among healthcare workers (HCWs), especially among nurses during the pandemic of COVID-19. The sample of the cross-sectional study consists of 201 employees of University Hospital. The Maslach Burnout Inventory-Human Services Survey for Medical Personnel (MBI-HSS MP) was used. An anonymous questionnaire was administered between 15 January and 1 February 2022. The majority of HCWs were female (79.4%). Overall, 69.2% displayed high levels of emotional exhaustion (EE), 35.3% high levels of depersonalization (DP), and 35.5% low levels of personal accomplishment (PA). Burnout was frequent among staff working in COVID units (EE 76.1%; DP 47.8%; and PA 46.7%). Burnout in EE and DP (70.7% and 36.6%, respectively) significantly prevailed in nurses working in COVID-19 units compared to non-frontline nurses (59.6 and 21.1%, respectively). Prevalence of burnout in PA was significantly higher in nurses working in non-COVID-19 units (47.4% vs. 29.3%). It is crucial to pay attention to the high prevalence of burnout syndrome in HCWs, especially in nurses, and not only in the frontline.

Assessment of a novel, easy-to-implement, aerosolized H2O2 decontamination method for single-use filtering facepiece respirators in case of shortage.

The COVID-19 pandemic has affected the world and caused a supply shortage of personal protection equipment, especially filtering facepiece respirators (FFP). This has increased the risk of many healthcare workers contracting SARS-CoV-2. Various strategies have been assessed to tackle these supply issues. In critical shortage scenarios, reusing single-use-designed respirators may be required. Thus, an easily applicable and reliable FFP2 (or alike) respirator decontamination method, allowing safe re-use of FFP2 respirators by healthcare personnel, has been developed and is presented in this study. A potent and gentle aerosolized hydrogen peroxide (12% wt) method was applied over 4 hr to decontaminate various brands of FFP2 respirators within a small common room, followed by adequate aeration and storage overnight. The microbial efficacy was tested on unused respirator pieces using spores of Geobacillus stearothermophilus. Further, decontamination effectiveness was tested on used respirators after one 12-hr shift by swabbing before and after the decontamination. The effects of up to ten decontamination cycles on the respirators' functionality were evaluated using material properties, the structural integrity of the respirators, and fit tests with subjects. The suggested H2O2 decontamination procedure was proven to be (a) sufficiently potent (no microbial recovery, total inactivation of biological indicators as well as spore inoculum on critical respirator surfaces), (b) gentle as no significant damage to the respirator structural integrity and acceptable fit factors were observed, and (c) safe as no H2O2 residue were detected after the defined aeration and storage. Thus, this easy-to-implement and scalable method could overcome another severe respirator shortage, providing enough flexibility to draft safe, effective, and logistically simple crisis plans. However, as highlighted in this study, due to the wealth of design and material used in different models and brands of respirators, the decontamination process should be validated for each FFP respirator model before its field implementation.