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To explore how the immune system controls clearance of SARS-CoV-2, we used a single-cell, mass cytometry-based proteomics platform to profile the immune systems of 21 patients who had recovered from SARS-CoV-2 infection without need for admission to an intensive care unit or for mechanical ventilation. We focused on receptors involved in interactions between immune cells and virus-infected cells. We found that the diversity of receptor repertoires on natural killer (NK) cells was negatively correlated with the viral clearance rate. In addition, NK subsets expressing the receptor DNAM1 were increased in patients who more rapidly recovered from infection. Ex vivo functional studies revealed that NK subpopulations with high DNAM1 expression had cytolytic activities in response to target cell stimulation. We also found that SARS-CoV-2 infection induced the expression of CD155 and nectin-4, ligands of DNAM1 and its paired coinhibitory receptor TIGIT, which counterbalanced the cytolytic activities of NK cells. Collectively, our results link the cytolytic immune responses of NK cells to the clearance of SARS-CoV-2 and show that the DNAM1 pathway modulates host-pathogen interactions during SARS-CoV-2 infection.
NK cell receptor and ligand composition influences the clearance of SARS-CoV-2
Introduction This study aims to develop and validate a questionnaire to assess workplace violence (WPV) domains in the healthcare setting. Methods The study used a mixed-method design. In Phase 1, qualitative methods for developing the questionnaire were employed, including literature review, focus-group discussion, expert evaluation, and pre-testing. During Phase 2, quantitative methods were employed for establishing the construct validity of the questionnaire. In Phase 1, experts from departments like emergency medicine, medicine, obstetrics and gynecology, psychiatry, trauma, anesthesia, and critical care unit participated. For Phase 2, data were collected from 213 participants; mean age (30.485.95) in metropolitan cities. Results The questionnaire consists of 37 items in five domains: (A) Forms of violence, (B) Impact of violent incidences, (C) Reporting of incidence, (D) Mitigation strategies, and (E) Risk factors. The Cronbachs alpha value of the questionnaire is 0.86, suggesting an excellent internal consistency. Conclusion A reliable and valid tool for gathering information regarding WPV in the healthcare system from around the world has been developed. The tool can be used to study the elements that may contribute to violence and its consequences, which will help policymakers curate various mitigation methods to safeguard WPV victims.
Development and Validation of a Questionnaire to Evaluate Workplace Violence in Healthcare Settings
The role of the mayor in times of crisis - In the spring of 2020, mayors were on the front line in dealing with the non-health aspects of the Covid-19 epidemic, in particular to manage the lockdown of the population This text draws on reports from the French Parliament and the Association of French Mayors to analyse their action, citing numerous examples Generally speaking, it highlights the indispensable role of the mayors on the ground, which is often little or poorly understood ? cole nationale d'administration Tous droits rservs pour tous pays
Le r?le du maire en temps de crise
Background Covid-19 has presented major challenges to face-to-face clinical encounters and facilitating safe and effective care remotely that is acceptable to children, parents and healthcare professionals is therefore of significant interest. Objectives To determine risks and benefits associated with a change in service delivery of paediatric minor injury follow up. Methods We conducted a prospective audit during introduction of a paediatric virtual fracture clinic (VFC) and associated same-day orthopaedic telephone advice line, staffed by orthopaedic consultants and registrars, on the outcomes of attendances to a dedicated paediatric emergency department at a district general hospital and associated minor injury units spanning nine weeks from April to June 2020, coinciding with the UK's first national lockdown due to Covid-19. Results were compared to a similar number of cases using standard face-to-face fracture clinics without an orthopaedic advice line during April 2019. Patients were identified through the department's established procedure for paediatric x-ray follow up and were included if they were suspected or confirmed to have an acute fracture or soft tissue injury. Patients were excluded from analysis if they presented with a soft tissue infection, wounds without fracture, non-acute injury or condition, were admitted to hospital or had safeguarding concerns. Initial and final diagnosis and management, number of radiographs, missed fractures, hospital attendances for the same injury, 'did not attend' episodes, adverse events and unplanned returns were recorded. Results There was a notable reduction in patient numbers during Covid-19 study period (1.4 vs 4.3 patients per day), commensurate with an overall drop in paediatric attendances during national lockdown. Reasons for attendances were broadly similar between VFC and standard practice groups, with comparable rates of admission (8.1 vs 11.6%). Compared to the standard practice group, the VFC group demonstrated a significant reduction in average face to face visits per patient (1.8 vs 2.9, p = 0.00001), average number of radiographs per patient (1.5 vs 1.8, p = 0.01) and no increase in rate of unplanned returns (0.06 vs 0.1 per patient). There were 2 instances of difficulty contacting parents for VFC appointments, which were both resolved by parents contacting fracture clinic. There were 3 instances of missed fractures in the VFC group;1 was missed in the emergency department and so unrelated to the introduction of VFC, 2 were missed after discussion with the advice line, of which 1 was detected after returning with on-going pain, put into a temporary back slab and discharged after 1 virtual clinic and the other which did not result in any change in management. There was 1 missed fracture in the standard practice group, but this was excluded from analysis due to missing records. Overall management in both groups was similar. Conclusions Face-to-face appointments for paediatric minor trauma can be safely replaced with a virtual fracture clinic system and associated advice line. This effectively saves each child one attendance per injury and one x-ray for every three children attending with minor injuries. Benefits would include reductions in missed school and work days for children and carers, and financial savings for healthcare organisations.
Virtual fracture clinics significantly reduce face-to-face contacts and radiographs in children presenting with minor trauma
Growth hormone releasing hormone (GHRH) antagonists enhance endothelial barrier function and counteract the LPS-induced lung endothelial hyperpermeability, the cardinal feature of the acute respiratory distress syndrome (ARDS). The unfolded protein response (UPR) is a multifaceted molecular mechanism, strongly involved in tissue defense against injury. The current study introduces the induction of UPR by GHRH antagonists, since those peptides induced several UPR activation markers, including the inositol-requiring enzyme-1 (IRE1), the protein kinase RNA-like ER kinase (PERK), and the activating transcription factor 6 (ATF6). On the other hand, the GHRH agonist MR-409 exerted the opposite effects. Furthermore, GHRH antagonists counteracted the kifunensine (UPR suppressor)-induced lung endothelial barrier dysfunction. Our observations suggest that UPR mediates, at least in part, the protective effects of GHRH antagonists in the lung microvasculature. To the best of our knowledge; this is the first study to provide experimental evidence in support of the hypothesis that UPR induction is a novel mechanism by which GHRH antagonists oppose severe human disease, including ARDS.
Involvement of the unfolded protein response in the protective effects of growth hormone releasing hormone antagonists in the lungs
Smoking rates are higher for people who use mental health services which contributes substantially to health inequalities. Smoking can lead to worse COVID-19 outcomes, yet it remains unclear whether smoking has changed for people who use mental health services. We examined smoking patterns in a large clinical cohort of people with SMI before and during the pandemic. We found high levels of nicotine dependence and heavier patterns of smoking. Whilst some people had reported quitting, it is likely that smoking inequalities have become further entrenched. Mental health services should seek to mitigate this modifiable risk and source of poor health.
How has the COVID-19 pandemic impacted on smoking and nicotine dependence among people with severe mental ill health? Analysis of linked data from a UK Closing the Gap Cohort
The Azores archipelago is the most suitable region for dairy production in Portugal, representing 30% of the overall Portuguese dairy production. It has a production system characterized by an average milk yield of 6216 kg/cow/year, and the predominance of pasture-based feeding and cows that have longer productive lives and lower incidence of metabolic/production diseases, such as acidosis or mastitis. The biggest problem with the Azores Islands dairy sector is the cost of transport, as the main markets are located in continental Portugal, over 1500 km away, and local dairy products have to compete with dairy products produced in mainland Portugal and in the rest of the European Union. Herein, the evolution of the dairy sector in the Azores Islands from 2007 to 2017 is presented. A SWOT (Strength, Weakness, Opportunity, and Threat) analysis was performed to find potential solutions to increase the value of the Azorean dairy sector. The most relevant solution considered was the valorization of the dairy production through three major aspects: higher milk quality, namely, better organoleptic properties; lower carbon footprint (not considering transport costs); and higher levels of animal welfare. Three examples are shown of such valorization: protected denomination of origin (PDO) cheeses, the happy cows program, and the production of an organic milk, from the Terceira Island. Some of these programs are relatively recent, so, it will be interesting to see how their sales and acceptance by consumers evolve, particularly under the current economic framework.
The dairy sector in the Azores Islands: possibilities and main constraints towards increased added value
Background: Vaccines have had a great impact on disease prevention and mortality reduction. Very rarely, vaccines also can result in serious adverse effects. In consideration of this fact, vaccine injury compensation programs have been implemented in many countries to compensate a vaccinee for associated adverse effects. The existing vaccine injury compensation system addresses routine immunization schemes. However, there are rising concerns about the compensation for adverse effects caused by new vaccines such as those developed for coronavirus disease 2019 (COVID-19). The objective of this article is to review the existing vaccine injury compensation programs in different countries. The review also highlights the necessity to include all upcoming new vaccines for COVID-19 and other emerging viral diseases in the compensation schemes. Methods: : Published articles relating to vaccine compensation injury programs, vaccines, injuries, disabilities, illnesses, and deaths resulting from vaccination were searched in data bases. Through a careful review of the abstracts, 25 relevant articles were selected for analysis. Results: : We identified 27 countries on four continents with vaccine injury compensation schemes: 17 countries in Europe, 7 countries in Asia, the United States, a Canadian Province and New Zealand. No programs were identified in Africa and in South America. Program design, funding, and eligibility for compensation vary vastly between countries. We identified 17 countries operating well-established vaccine injury compensation programs. However, minimal information is available on numerous other countries. Conclusion: We have identified 27 countries operating vaccine injury compensation programs. In Canada, Quebec is the only province with a scheme;however, discussions are ongoing in Canada for nationwide implementation in light of COVID 19. Study limitations include limited scientific material, which hindered our research. Additional data concerning payout for each type of injury and the number of claimants related to a specific vaccine injury worldwide could provide a more comprehensive analysis.
Current situation of vaccine injury compensation program and a future perspective in light of COVID-19 and emerging viral diseases
Mucociliary clearance, mediated by a coordinated function of cilia bathing in the airway surface liquid (ASL) on the surface of airway epithelium, protects the host from inhaled pathogens and is an essential component of the innate immunity. ASL is composed of the superficial mucus layer and the deeper periciliary liquid. Ion channels, transporters, and pumps coordinate the transcellular and paracellular movement of ions and water to maintain the ASL volume and mucus hydration. microRNA (miRNA) is a class of non-coding, short single-stranded RNA regulating gene expression by post-transcriptional mechanisms. miRNAs have been increasingly recognized as essential regulators of ion channels and transporters responsible for ASL homeostasis. miRNAs also influence the airway host defense. We summarize the most up-to-date information on the role of miRNAs in ASL homeostasis and host-pathogen interactions in the airway and discuss concepts for miRNA-directed therapy.
The Role of MicroRNA in the Airway Surface Liquid Homeostasis
COVID-19 is spreading in a global pandemic that is endangering human life and health. Therefore, there is an urgent need to target COVID-19 to find effective treatments for this emerging acute respiratory infection. Viral Papain-Like cysteine protease (PLpro), similar to papain and the cysteine deubiquitinase enzyme, has been a popular target for coronavirus inhibitors, as an indispensable enzyme in the process of coronavirus replication and infection of the host. Combined structure-based virtual screening, molecular dynamics (MD) simulation, and molecular mechanics/Generalized Born surface area (MM/GBSA) free energy calculation approaches were utilized for identification of PLpro inhibitors. Four compounds (F403_0159, F112_0109, G805_0497, D754_0006) with diverse chemical scaffolds were retrieved as hits based on docking score and clustering analysis. Molecular dynamics simulations indicated that the contribution of van der Waals interaction dominated the binding free energies of these compounds, which may be attributed to the hydrophobicity of active site of PLpro from COVID-19. Moreover, all four compounds formed conservative hydrogen bonds with the residues Asp164, Gln269, and Tyr273. We hoped that these four compounds might represent the promising chemical scaffolds for further development of novel PLpro inhibitors against COVID-19.
Discovery of small molecule PLpro inhibitor against COVID-19 using structure-based virtual screening, molecular dynamics simulation, and molecular mechanics/Generalized Born surface area (MM/GBSA) calculation
Background: Concern for the development of actions against COVID-19 has continued to grow since February 2020. Government responses remain a crucial part of preventing virus transmission through policy formulation and strengthening national capacity. Methods: This study has used quantitative analysis, using secondary data from 177 countries. The variables consist of Global Health Security (GHS) category and COVID-19 pandemic. An analysis of the appropriateness of the governments policy response in dealing with the COVID-19 pandemic was carried out by comparing the two variables. Results: The study indicated a significant relationship between global health security category and pandemic score (P < 0.01). There were 37 countries out of 177 (20.9%) categorized as under-reaction and least-reaction. Conclusion: Pandemic COVID-19 score, rated based on doubling time, is directly significant with the health security category. The government should improve its responsiveness and preparation to improve national capacity during the novel coronavirus pandemic.
Global policy responses to the COVID-19 pandemic: proportionate adaptation and policy experimentation: a study of country policy response variation to the COVID-19 pandemic
Vaccination is the most effective way to provide long-lasting immunity against viral infection; thus, rapid assessment of vaccine acceptance is a pressing challenge for health authorities. Prior studies have applied survey techniques to investigate vaccine acceptance, but these may be slow and expensive. This study investigates 29 million vaccine-related tweets from August 8, 2020 to April 19, 2021 and proposes a social media-based approach that derives a vaccine acceptance index (VAI) to quantify Twitter users opinions on COVID-19 vaccination. This index is calculated based on opinion classifications identified with the aid of natural language processing techniques and provides a quantitative metric to indicate the level of vaccine acceptance across different geographic scales in the U.S. The VAI is easily calculated from the number of positive and negative Tweets posted by a specific users and groups of users, it can be compiled for regions such a counties or states to provide geospatial information, and it can be tracked over time to assess changes in vaccine acceptance as related to trends in the media and politics. At the national level, it showed that the VAI moved from negative to positive in 2020 and maintained steady after January 2021. Through exploratory analysis of state- and county-level data, reliable assessments of VAI against subsequent vaccination rates could be made for counties with at least 30 users. The paper discusses information characteristics that enable consistent estimation of VAI. The findings support the use of social media to understand opinions and to offer a timely and cost-effective way to assess vaccine acceptance.
Dynamic assessment of the COVID-19 vaccine acceptance leveraging social media data
Objective: This study aimed to examine and evaluate the knowledge levels, attitudes and anxiety sources regarding coronavirus disease-2019 (COVID-19) infection in dentistry students in clinical practice Materials and Methods: Fourth- and fifth-year dentistry students of Aydin Adnan Menderes University and Akdeniz University were selected for this study For data collection, a questionnaire survey was performed The questionnaire contained 34 items on demographic data, knowledge level about COVID-19 infection and attitudes and anxiety sources about their education Descriptive statistical methods and the Pearson chi-square test were used to analyse data P<0 05 was statistically significant Results: A total of 137 students, including 75 females (54 7%) and 62 males (45 3%), participated in the study Significantly higher levels of negativity and anxiety due to COVID-19 was found in female participants than in male participants, based on their responses to the following questions: "Do you believe that the lack of face-toface training due to COVID-19 will negatively affect your working life?";"Do you worry about graduating having completed clinical practice without direct patient care?";"Do you worry about practising your job because of the coronavirus?"and the p values were found 0 019, 0 002 and 0 009, respectively The answers for these questions were not related to the graduation degree Conclusion: The results reveal that female students demonstrated higher stress levels than male students based on the responses to some questions Moreover, responses to the same questions were not related to the graduation degree Further larger studies will give more accurate outcomes
Examination of the knowledge levels, attitudes and anxiety sources regarding coronavirus disease-2019 infection in dentistry students in clinical practice
BACKGROUND: Global Health Leadership (GHL) programs are essential for training emerging health care professionals to be effective leaders. Synthesizing knowledge acquired through experience implementing GHL programs can inform future recommendations for GHL. OBJECTIVE: To describe the lessons learned, highlighting gaps, challenges and opportunities, during implementation of two GHL capacity building programs, namely the Afya Bora Consortium Fellowship in Global Health Leadership and the Sustaining Technical and Analytic Resources (STAR) fellowship and internship program for global health professionals. METHODS: A mixed methods case-comparison study was conducted, using qualitative data (expert opinion) collected from the Program Directors in order to understand the experiences of the two GHL programs. A structured response guide was used to assess the overall experience in GHL program implementation, operational challenges and reported gaps. Afya Bora and STAR have been implemented for 8 and 2.5 years respectively. Thus, the analysis reflects a snapshot of the two programs at different stages. FINDINGS: The results reflect knowledge gained through extensive experience in implementing the two GHL programs. Afya Bora has trained 188 multi-disciplinary fellows, and 100% of the African fellows are engaged in leadership positions in government departments and non-governmental organizations (NGOs) in their countries. STAR has placed 147 participants (89 fellows and 58 interns) in more than 25 countries globally. Both programs were successful in strengthening south-south and north-south collaborations for a common goal of improving global health. Implementation of both fellowships identified room for improvement in operational procedures and financing of the programs, and highlighted knowledge and skills gaps, as well as challenges in sustainability of the training programs. CONCLUSIONS: Afya Bora and STAR have had significant impact and have contributed to changing the leadership landscape in global health. Future GHL programs should address sustainability in terms of financing, delivery modalities and domestic integration of knowledge.
Gaps, Challenges, and Opportunities for Global Health Leadership Training
The ongoing COVID-19 pandemic currently involves millions of people worldwide Radiology plays an important role in the diagnosis and management of patients, and chest computed tomography (CT) is the most widely used imaging modality An automatic method to characterize the lungs of COVID-19 patients based on individually optimized Hounsfield unit (HU) thresholds was developed and implemented Lungs were considered as composed of three components—aerated, intermediate, and consolidated Three methods based on analytic fit (Gaussian) and maximum gradient search (using polynomial and original data fits) were implemented The methods were applied to a population of 166 patients scanned during the first wave of the pandemic Preliminarily, the impact of the inter-scanner variability of the HU-density calibration curve was investigated Results showed that inter-scanner variability was negligible The median values of individual thresholds th1 (between aerated and intermediate components) were −768, −780, and −798 HU for the three methods, respectively A significantly lower median value for th2 (between intermediate and consolidated components) was found for the maximum gradient on the data (−34 HU) compared to the other two methods (−114 and −87 HU) The maximum gradient on the data method was applied to quantify the three components in our population—the aerated, intermediate, and consolidation components showed median values of 793 ±499 cc, 914 ±291 cc, and 126 ±111 cc, respectively, while the median value of the first peak was −853 ±56 HU
An Automatic Approach for Individual HU-Based Characterization of Lungs in COVID-19 Patients
BACKGROUND: This study aims to describe the radiological findings in chest radiographs (CXRs) of patients with coronavirus disease (COVID-19) and the Middle East respiratory syndrome (MERS) and compare the radiological patterns of the two diseases. METHOD: A retrospective cohort study was conducted in a tertiary care hospital in the Southern region of Saudi Arabia. The CXRs were evaluated for the presence and distribution of ground-glass opacities (GGO), consolidation, pleural effusions, pneumothorax, cavitation, and nodules. RESULTS: A total of 120 CXRs from 15 MERS and six COVID-19 patients were assessed. In the first available CXR, GGO was present in 11 (73%) of the MERS patients (18% located in the middle zones and 67% located peripherally) and in 100% of COVID-19 patients (peripheral and middle zone involvement in all patients). In the first available CXRs, consolidation was present in 10 MERS patients (67%) and all six COVID-19 patients, while it was present in all patients of both groups when all the available CXRs were considered. Confluent consolidation was present in 47% of the MERS patients and 50% of COVID-19 patients. All the fatal cases had confluent consolidation and radiological signs of acute respiratory distress syndrome (ARDS). Pneumothorax was present in 13% of patients, with 100% mortality, and pleural effusion was present in 47% of patients, with 57% mortality. Lung nodules were present in one patient of each group. CONCLUSION: COVID-19 patients showed earlier development of GGO and consolidation with greater involvement of the middle and peripheral lung zones. Confluent consolidation and ARDS-like radiological findings were associated with high mortality. Pneumothorax and pleural effusions were more frequent in MERS patients, with high associated mortality.
Coronavirus Disease (COVID-19) compared with Middle East Respiratory Syndrome (MERS): A Radiological Perspective
Sleep disturbances in early childhood are associated with mood and anxiety disorders. Children also exhibit sleep disruptions, such as nighttime awakenings, nightmares, and difficulties falling asleep, in conjunction with adverse events and stress. Prior studies have examined independently the role of sleep on adaptive processing, as well as the effects of stress on sleep. However, how childhood sleep and children's adaptive behavior (i.e., coping strategies) bidirectionally interact is currently less known. Using a within-subjects design and actigraphy-measured sleep from 16 preschool-aged children (M(age) = 56.4 months, SD = 10.8, range: 36C70 months), this study investigated how prior sleep patterns relate to children's coping during a potentially stressful event, the COVID-19 pandemic, and how prior coping skills may influence children's sleep during the pandemic. Children who woke earlier had greater negative expression both before and during the pandemic. During the pandemic, children slept longer and woke later on average compared to before the pandemic. Additionally, for children engaged in at-home learning, sleeping longer was associated with less negative expression. These findings highlight how sleep behaviors and coping strategies are related, and the stability of this relationship under stress.
Sleep and Coping in Early Childhood During the COVID-19 Pandemic
Oxylipins are an important class of bioactive lipids derived from polyunsaturated fatty acids. They can be both pro- and anti-inflammatory and function as important mediators in various pathological conditions. However, comprehensive analysis of oxylipins still remains a challenge because of their low abundance in plasma and the dominance of structurally similar isomeric species. Herein, we describe a simple and rapid method to comprehensively analyze oxylipins in blood plasma, which utilizes solid-phase extraction in 96-well format for efficient sample cleanup. Separation and detection of more than 130 oxylipins is accomplished by liquid chromatography-tandem mass spectrometry with multiple reaction monitoring in negative-ion mode. The absolute concentrations of oxylipins in human plasma are determined using the calibration curves constructed from internal standards. Detailed methods and precautions are presented for a successful adoption of this method in analytical laboratory.
Quantification of Plasma Oxylipins Using Solid-Phase Extraction and Reversed-Phase Liquid Chromatography-Triple Quadrupole Mass Spectrometry
1 ABSTRACT Objective Correct use of face masks is required for their efficacy in preventing possible droplet infections with SARS-CoV-2. We tried to provide information about differences in the distribution of gender and age groups wearing face masks incorrectly. Design Pilot field study Methods Visual observation of mask use in public, not age- and gender-related places in central European large cities regarding incorrect mask-wearing (n=523); statistical analysis (nominal scale) in terms of gender and estimated age group using the total numbers, binomial test and chi-square test. Results There is no significant difference (binomial test: p-value = 0.43) in mask misuse between the genders (female: 271 (51.8%), male: 252 (48.2%) and 0 non-binary individuals (0%)). There is a significant difference (chi-square test: p-value < 2.2e-16) in age group distribution (170 young 10-29 years (32.5%), 261 middle-aged 30-59 years (49.9%), 92 older adults []60 years (17.6%)). In total numbers, the highest counts were observed in middle-aged persons with 261 counts (49.9%). Conclusion Our study shows an uneven age-distribution of people wearing the face mask in public improperly. Keywords Coronavirus, SARS-CoV-2, COVID-19, Community, Face mask, Prevention
Gender- and age-related differences in misuse of face masks in COVID-19 prevention in central European cities
The work presented in this paper uses empirical evidence to highlight the important role digital technology plays in mitigating a pandemic's economic disruption As extensive datasets including the effect of the current COVID-19 pandemic are still unavailable, this study provides an assessment of the role of digitization at the time of SARS in 2003 Results are robust in pointing out that those countries with better broadband connectivity were able to mitigate some of the economic losses incurred by the pandemic While anecdotal evidence is plentiful even for COVID-19, this study provides rigorous analysis to support that a reliable telecommunications infrastructure and a high level of digitization is crucial to keep the economy running under pandemic conditions These results provide valuable evidence for the current context of COVID-19, which has resulted in several national lockdowns around the world In consequence, we believe that the public and private sectors must collaborate and work together to promote the enhancement of the digital ecosystem In the long run, a suitable regulatory framework seems crucial to stimulate private investments to close the digital supply gap, as well as promoting the digitization of business process and the training of the workforce to acquire digital skills In the short term, we discuss several measures that can be taken to accommodate the expected increases in internet traffic in such circumstances and maintain the quality of service
Can digitization mitigate the economic damage of a pandemic? Evidence from SARS