Lipid Nanoparticles as Promising Carriers for mRNA Vaccines for Viral Lung Infections.

In recent years, there has been an increase in deaths due to infectious diseases, most notably in the context of viral respiratory pathogens. Consequently, the focus has shifted in the search for new therapies, with attention being drawn to the use of nanoparticles in mRNA vaccines for targeted delivery to improve the efficacy of these vaccines. Notably, mRNA vaccine technologies denote as a new era in vaccination due to their rapid, potentially inexpensive, and scalable development. Although they do not pose a risk of integration into the genome and are not produced from infectious elements, they do pose challenges, including exposing naked mRNAs to extracellular endonucleases. Therefore, with the development of nanotechnology, we can further improve their efficacy. Nanoparticles, with their nanometer dimensions, move more freely in the body and, due to their small size, have unique physical and chemical properties. The best candidates for vaccine mRNA transfer are lipid nanoparticles (LNPs), which are stable and biocompatible and contain four components: cationic lipids, ionizable lipids, polyethylene glycols (PEGs), and cholesterol, which are used to facilitate cytoplasmic mRNA delivery. In this article, the components and delivery system of mRNA-LNP vaccines against viral lung infections such as influenza, coronavirus, and respiratory syncytial virus are reviewed. Moreover, we provide a succinct overview of current challenges and potential future directions in the field.

Real-World Evidence on the Effectiveness of Plexiglass Barriers in Reducing Aerosol Exposure.

Reprinted with permission, Cleveland Clinic Foundation ©2022. All Rights Reserved. Background: Barriers are commonly installed in workplace situations where physical distancing cannot be maintained to reduce the risk for transmission of respiratory viruses. Although some types of barriers have been shown to reduce exposure to aerosols in laboratory-based testing, limited information is available on the efficacy of barriers in real-world settings. Methods: In an acute care hospital, we tested the effectiveness of in-use plexiglass barriers in reducing exposure of staff to aerosolized particles. A nebulizer was used to release 5% NaCl aerosol 1 meter from staff members with and without the barrier positioned between the point of aerosol release and the hospital staff. Particle counts on the staff side of the barrier were measured using a 6-channel particle counter. A condensed moisture (fog) generating device was used to visualize the airflow patterns. Results: Of 13 in-use barriers tested, 6 (46%) significantly reduced aerosol particle counts detected behind the barrier, 6 (46%) reduced particle counts to a modest, non-significant degree, and 1 (8%) significantly increased particle counts behind the barrier. Condensed moisture fog accumulated in the area where staff were seated behind the barrier that increased particle exposure, but not behind the other barriers. After repositioning the ineffective barrier, the condensed moisture fog no longer accumulated behind the barrier and aerosol exposure was reduced. Conclusion: In real-world settings, plexiglass barriers vary widely in effectiveness in reducing staff exposure to aerosols, and some barriers may increase risk for exposure if not positioned correctly. Devices that visualize airflow patterns may be useful as simple tools to assess barriers.

Getting Serious About People Over Profit: Addressing Burnout by Establishing Meaning and Connection

Interventions to promote healthy sleep may reduce physician burnout susceptibility.5 An extensive study of physicians reported sleep-related impairment in 40% of attending physicians and 51% of house staff physicians.6 There was large correlation between sleeprelated impairment and interpersonal disengagement, work exhaustion, and overall burnout.6 After adjustment for other variables, high sleep impairment levels increased the odds of self-reporting a clinically significant medical error by 96%.6 Besides medical errors, sleep-related impairment and occupational distress have also been associated with unsolicited patient complaints. Activities that enhance social supports (e.g., peer support programs and Balint groups) and add meaning to work (e.g., professional development time, mentorship, time to develop connections with patients, etc.) are likely to provide some benefit, as they support physicians' capacity to maintain perspective, sense of purpose, and enhance sense of control over their situation.9,10 One study showed such a group normalized struggles, reduced isolation, and provided new strategies for navigating challenging interactions.11 In another study, self-facilitated physician small-group meetings improved burnout, symptoms of depression, and job satisfaction.12 Although rates of burnout among physicians have grown, physicians are resilient when compared to other occupational groups. A recent review found the rate of burnout among nurses working in hospitals ranged widely from 5% to 50%, based on specialty differences and geographical regions.14 More specifically, the review indicated the overall prevalence of emotional exhaustion was 34.1%, of depersonalization 12.6%, and of lack of personal accomplishment 15.2%.15 This same review took COVID-19 into account and noted nurse burnout risk factors as younger age, decreased social support, low family and colleague readiness to cope with COVID-19 outbreak, increased perceived threat of COVID-19, longer working time in quarantine areas, working in a high-risk environment, working in hospitals with inadequate and insufficient material and human resources, increased workload, and lower level of specialized training regarding COVID-19.15 Burnout has many consequences in nurses. Emotional exhaustion is negatively associated with the quality and safety of care, patient satisfaction, nurses' organizational commitment, and productivity.14 Nurse burnout has been a significant factor in predicting medication-associated errors.16 Protective factors in nurses include belief in readiness to cope with COVID-19 outbreaks, willingness to participate in frontline work, prior training and experience in COVID-19 patients' management, safe practices, and increased social support.15 Empathy and nursing organizational climate have been found to be protective against burnout, suggesting this could be targeted in managerial interventions.17 Nursing surveys of three types of work engagement (i.e., vigor, dedication, and absorption) and resiliency suggested some protection from burnout.18 Mindfulness-based interventions could potentially have a protective effect for burnout in nurses.19 (See Table 2 for an overview of how burnout impacts feelings about careers in nurses and physicians.) COVID-19 PANDEMIC AS ACCELERANT TO THE BURN Healthcare workers were already hurting before 2020 and the start of the COVID-19 pandemic.

Public opinion of the Irish “COVID Tracker” digital contact tracing App: A national survey

Objective This study aims to gather public opinion on the Irish “COVID Tracker” digital contact tracing (DCT) App, with particular focus on App usage, usability, usefulness, technological issues encountered, and potential changes to the App. Methods A 35-item online questionnaire was deployed for 10 days in October 2020, 3 months after the launch of the Irish DCT App. Results A total of 2889 completed responses were recorded, with 2553 (88%) respondents currently using the App. Although four in five users felt the App is easy to download, is easy to use and looks professional, 615 users (22%) felt it had slowed down their phone, and 757 (28%) felt it had a negative effect on battery life. Seventy-nine percent of respondents reported the App's main function is to aid contact tracing. Inclusion of national COVID-19 trends is a useful ancillary function according to 87% of respondents, and there was an appetite for more granular local data. Overall, 1265 (44%) respondents believed the App is helping the national effort, while 1089 (38%) were unsure. Conclusions DCT Apps may potentially augment traditional contact tracing methods. Despite some reports of negative effects on phone performance, just 7% of users who have tried the App have deleted it. Ancillary functionality, such as up-to-date regional COVID-19, may encourage DCT App use. This study describes general positivity toward the Irish COVID Tracker App among users but also highlights the need for transparency on effectiveness of App-enabled contact tracing and for study of non-users to better establish barriers to use.

Virtual screening-driven drug discovery of SARS-CoV2 enzyme inhibitors targeting viral attachment, replication, post-translational modification and host immunity evasion infection mechanisms.

The novel coronavirus SARS-CoV2, the causative agent of the pandemic disease COVID-19, emerged in December 2019 forcing lockdown of communities in many countries. The absence of specific drugs and vaccines, the rapid transmission of the virus, and the increasing number of deaths worldwide necessitated the discovery of new substances for anti-COVID-19 drug development. With the aid of bioinformatics and computational modelling, ninety seven antiviral secondary metabolites from fungi were docked onto five SARS-CoV2 enzymes involved in viral attachment, replication, post-translational modification, and host immunity evasion infection mechanisms followed by molecular dynamics simulation and in silico ADMET prediction (absorption, distribution, metabolism, excretion and toxicity) of the hit compounds. Thus, three fumiquinazoline alkaloids scedapin C (15), quinadoline B (19) and norquinadoline A (20), the polyketide isochaetochromin D1 (8), and the terpenoid 11a-dehydroxyisoterreulactone A (11) exhibited high binding affinities on the target proteins, papain-like protease (PLpro), chymotrypsin-like protease (3CLpro), RNA-directed RNA polymerase (RdRp), non-structural protein 15 (nsp15), and the spike binding domain to GRP78. Molecular dynamics simulation was performed to optimize the interaction and investigate the stability of the top-scoring ligands in complex with the five target proteins. All tested complexes were found to have dynamic stability. Of the five top-scoring metabolites, quinadoline B (19) was predicted to confer favorable ADMET values, high gastrointestinal absorptive probability and poor blood-brain barrier crossing capacities.Communicated by Ramaswamy H. Sarma.

Kaggle Competitions in the Classroom: Retrospectives and Recommendations

Ruiz et al discuss the use of Kaggle in classrooms. Kaggle is an online data science platform best known for its public machine learning competitions. Since its inception in 2008, Kaggle has hosted thousands of competitions to advance research on a myriad of topics ranging from satellite imagery feature detection to COVID-19 research analysis. Besides hosting these global competitions, Kaggle has grown into an expansive data science educational platform that offers full courses, an open-source dataset repository, and a feature known as Kaggle InClass competitions (KICs). These KICs are contests specifically tailored for use in an academic setting that are completely customizable by the hosting professor or teaching assistant. In turn, the Kaggle platform provides a leaderboard, centralized location to access the competition data, and support for various popular code libraries.

Not One, But Five: Virtual Screening-Driven Drug Discovery of SARS-CoV2 Enzyme Inhibitors Targeting Viral Attachment, Replication and Post-Translational Infection Mechanisms (preprint)

The novel coronavirus SARS-CoV2, the causative agent of the worldwide pandemic disease COVID-19, emerged in December 2019 forcing lockdown of communities in many countries. The absence of specific drugs and vaccines, the rapid transmission of the virus, and the increasing number of deaths worldwide have necessitated the need to discover substances that can be tapped for drug development. With the aid of bioinformatics and computational modelling, ninety seven secondary metabolites from fungi previously reported to exhibit antiviral properties were docked onto SARS-CoV2 enzymes involved in viral attachment, replication and post-translational mechanisms followed by in silico ADMET prediction (absorption, distribution, metabolism, excretion and toxicity) of the hit compounds. Thus, two fumiquinazoline alkaloids quinadoline B (19), scedapin C (15), and the polyketide isochaetochromin D1 (8) exhibited high binding affinities depending on the target protein. The compounds were active against the cysteine proteases, papain-like protease (PLpro) and chymotrypsin-like protease (3CLpro) which are involved in post-translational modifications, RNA-directed RNA polymerase (RdRp) which is essential in viral replication, non-structural protein 15 (nsp15) which is involved in evasion of host immunity, and the spike protein which is responsible for binding to GRP78. Quinadoline B (19) was predicted to confer favorable ADMET values, high gastrointestinal absorptive probability and poor blood-brain barrier crossing capacities.