Advanced engineering of third-generation lysins and formulation strategies for clinical applications

One of the possible solutions for the current antibiotic resistance crisis may be found in (often bacteriophage-derived) peptidoglycan hydrolases. The first clinical trials of these natural enzymes, coined here as first-generation lysins, are currently ongoing. Moving beyond natural endolysins with protein engineering established the second generation of lysins. In second-generation lysins, the focus lies on improving antibacterial and biochemical properties such as antimicrobial activity and stability, as well as expanding their activities towards Gram-negative pathogens. However, solutions to particular key challenges regarding clinical applications are only beginning to emerge in the third generation of lysins, in which protein and biochemical engineering efforts focus on improving properties relevant under clinical conditions. In addition, increasingly advanced formulation strategies are developed to increase the bioavailability, antibacterial activity, and half-life, and to reduce pro-inflammatory responses. This review focuses on third-generation and advanced formulation strategies that are developed to treat infections, ranging from topical to systemic applications. Together, these efforts may fully unlock the potential of lysin therapy and will propel it as a true antibiotic alternative or supplement

Evaluation of the potential for virus dispersal during hand drying: a comparison of three methods

Aims To use a MS2 bacteriophage model to compare three hand-drying methods, paper towels (PT), a warm air dryer (WAD) and a jet air dryer (JAD), for their potential to disperse viruses and contaminate the immediate environment during use. Methods and Results Participants washed their gloved hands with a suspension of MS2 bacteriophage and hands were dried with one of the three hand-drying devices. The quantity of MS2 present in the areas around each device was determined using a plaque assay. Samples were collected from plates containing the indicator strain, placed at varying heights and distances and also from the air. Over a height range of 0.15-1.65 m, the JAD dispersed an average of >60 and >1300-fold more plaque-forming units (pfu) compared to the WAD and PT (P 20 and >190-fold more pfu in total compared to WAD and PT at all distances tested up to 3 m (P 50 and >100-fold more pfu compared to the WAD and PT (P <0.001), respectively. Conclusions Use of the JAD lead to significantly greater and further dispersal of MS2 bacteriophage from artificially contaminated hands when compared to the WAD and PT. Significance and Impact of Study The choice of hand drying device should be considered carefully in areas where infection prevention concerns are paramount, such as healthcare settings and the food industry

Clinical Experience in Adults and Children Treated with Intravenous Peramivir for 2009 Influenza A (H1N1) Under an Emergency IND Program in the United States

Peramivir, an investigational intravenous neuraminidase inhibitor, was given to 31 hospitalized patients with severe viral pneumonia during the 2009 H1N1 influenza pandemic under the Emergency IND regulations. The drug was generally well tolerated and associated with recovery in most patientes

Characteristics of HIV seroprevalence of visitors to public health centers under the national HIV surveillance system in Korea: cross sectional study

<p>Abstract</p> <p>Background</p> <p>In Korea, the cumulative number of HIV-infected individuals was smaller than those of other countries. Mandatory HIV tests, dominating method until 1990's, have been gradually changed to voluntary HIV tests. We investigated HIV seroprevalence status and its characteristics of visitors to Public Health Centers (PHCs), which conducted both mandatory test and voluntary test under the national HIV/STI surveillance program.</p> <p>Methods</p> <p>We used HIV-testing data from 246 PHCs in 2005 through the Health Care Information System. The number of test taker was calculated using the code distinguished by the residential identification number. The subjects were classified into four groups by reason for testing; General group, HIV infection suspected group (HIV ISG), HIV test recommended group (HIV TRG), and sexually transmitted infection (STI) risk group.</p> <p>Results</p> <p>People living with HIV/AIDS were 149 (124 male and 25 female) among 280,456 individuals tested at PHCs. HIV seroprevalence was 5.3 per 10,000 individuals. Overall, the male revealed significantly higher seroprevalence than the female (adjusted Odds Ratio (adj. OR): 6.2; CI 3.8–10.2). Individuals aged 30–39 years (adj. OR: 2.6; CI 1.7–4.0), and 40–49 years (adj. OR: 3.8; CI 2.4–6.0) had higher seroprevalence than 20–29 years. Seroprevalence of HIV ISG (voluntary test takers and cases referred by doctors) was significantly higher than those of others. Foreigners showed higher seroprevalence than native Koreans (adj. OR: 3.8; CI 2.2–6.4). HIV ISG (adj. OR: 4.9; CI 3.2–7.5), and HIV TRG (adj. OR: 2.6; CI 1.3–5.4) had higher seroprevalence than General group.</p> <p>Conclusion</p> <p>A question on the efficiency of current mandatory test is raised because the seroprevalence of mandatory test takers was low. However, HIV ISG included voluntary test takers was high in our result. Therefore, we suggest that Korea needs to develop a method encouraging more people to take voluntary tests at PHCs, also to expand the anonymous testing centers and Voluntary Counselling and Testing Program (VCT) for general population to easily access to HIV testing.</p

Contextual characteristics of adults’ drinking occasions and their association with levels of alcohol consumption and acute alcohol‐related harm : a mapping review

Background and Aims There is a growing literature using event‐level methods to estimate associations between contextual characteristics of drinking occasions, consumption levels, and acute harms. This literature spans many research traditions and has not been brought together as a whole. This mapping review aimed to identify and describe the theoretical approaches to conceptualising drinking occasions, study designs, predictors, and outcome measures used in existing research with a view to identifying dominant approaches, research gaps and areas for further synthesis. Methods Eligible papers studied adults’ drinking occasions using quantitative event‐level methods and considered one or more contextual characteristics (e.g. venue, timing, or company) and at least one event‐level consumption or acute alcohol‐related harm outcome. We systematically searched Ovid MEDLINE, PsycInfo, and the Web of Science Social Sciences Citation Index, extracting data on studies’ theoretical approach, data collection methods, settings, populations, drinking occasion characteristics, and outcome measures. Results Searches identified 278 eligible papers (from 1975 to 2019), predominantly published after 2010 (n=181; 65.1%). Most papers reported research conducted in the United States (n=170; 61.2%) and half used student participants (n=133; 47.8%). Papers typically lacked a stated theoretical approach (n=203; 73.0%). Consistent with this, only 53 (19.1%) papers studied three or more occasion characteristics and most used methods that assume occasion characteristics do not change during an occasion (n=189; 68.0%). The most common outcome type considered was consumption (n=224; 80.6%) and only a few papers studied specific acute harm outcomes such as unprotected sex (n=24; 8.6%), drink driving (n=14; 5.0%) or sexual violence (n=9; 3.2%). Conclusions Studies from 1975 to 2019 using event‐level methods to estimate associations between contextual characteristics of drinking occasions, consumption levels, and acute harms were largely focused on students and consumption outcomes and most have considered a limited range of contextual characteristics