关键词： Allergies   Biodiversity antigen richness   Civilization diseases   Contacts with nature   Infectious diseases   Wildlife   MICROBIOTA   IMPACT   HYGIENE   FARM   HYPOTHESIS   PREVALENCE   EXPRESSION   RECEPTORS   DISEASES   COHORT  

摘要： The gradual decrease in the prevalence of serious infectious diseases over the last century has been followed by increase in so called "modern" diseases, including allergies, chronic inflammatory conditions, psychiatric, and metabolic disorders. Between 2019 and 2022, public awareness of the threat of infectious diseases in humans was renewed by the global pandemic of a new type of a coronavirus, the SARS-COV-2. This public interest opened improved possibilities to test hypotheses on the factors associated with inter-individual variation in susceptibility to infectious and "modern" diseases. Based on the Hygiene hypothesis and Biodiversity hypothesis, we predicted that contacts with natural environment and wildlife in childhood and/or in adulthood can improve general health and decrease the risks of severe COVID-19 progression or prevalence of the "modern" diseases, namely the allergies. Here we report the results of an online, self-evaluating questionnaire survey conducted in the Czech Republic, where we contrasted selected health issues, and linked them to the living environment, including the level of contacts with biodiversity. In a sample of 1188 respondents, we revealed a significant association of time spent in nature or contacts with biodiversity with physical and mental health, or incidence of allergies. This is unlike the COVID-19 progression, which was related to age, physical health, smoking, allergies, and interaction of age with smoking, but not to contacts with the natural environmental diversity. Our findings regarding to physical and mental health and allergies are in agreement with the Biodiversity hypothesis of allergy and, linking human and environmental health, they urge for One Health approach application.

关键词： 3CL protease   ibuzatrelvir   antivirals   SARS-CoV-2   COVID   crystallography   NIRMATRELVIR  

摘要： Ibuzatrelvir (1) was recently disclosed and patented by Pfizer for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has received fast-track status from the USA Food and Drug Administration (FDA) and has entered phase III clinical trials as a possible replacement for Paxlovid. Like nirmatrelvir (2) in Paxlovid, this orally active drug candidate is designed to target viral main proteases (M-pro) through reversible covalent interaction of its nitrile warhead with the active site thiol of the chymotrypsin-like cysteine protease (3CL protease). Inhibition of M-pro hinders the processing of the proteins essential for viral replication in vivo. However, ibuzatrelvir apparently does not require ritonavir (3), which is coadministered in Paxlovid to block human oxidative metabolism of nirmatrelvir. Here, we report the crystal structure of the complex of ibuzatrelvir with the active site of SARS-CoV-2 M-pro at 2.0 & Aring; resolution. In addition, we show that ibuzatrelvir also potently inhibits the M-pro of Middle East respiratory syndrome-related coronavirus (MERS-CoV), which is fortunately not widespread but can be dangerously lethal (similar to 36% mortality). Co-crystal structures show that the binding mode of the drug to both active sites is similar and that the trifluoromethyl group of the inhibitor fits precisely into a critical S2 substrate binding pocket of the main proteases. However, our results also provide a rationale for the differences in potency of ibuzatrelvir for these two proteases due to minor differences in the substrate preferences leading to a weaker H-bond network in MERS-CoV M-pro. In addition, we examined the reversibility of compound binding to both proteases, which is an important parameter in reducing off-target effects as well as the potential immunogenicity. The crystal structures of the ibuzatrelvir complexes with M-pro of SARS-CoV-2 and of MERS-CoV will further assist drug design for coronaviral infections in h

关键词： COVID-19   Health policy   Health systems evaluation  

摘要： In February 2020, GloPID-R coconvened the Global Research and Innovation Forum with WHO resulting in a Global Research Roadmap for COVID-19, which outlined immediate and mid-term to long-term research priority areas for focusing the global research effort.2 This roadmap has been instrumental in setting the agenda for research for global COVID-19 prevention and control.3 Multiple further research priority setting activities employing varying methodologies were undertaken during the pandemic. Monitoring and evaluation to enable living research roadmaps: it is crucial for assessment processes for progress against research agenda to be promoted particularly in a fast-moving pandemic where research needs rapidly evolve. The PSI Policy and Practice Research Group is undertaking a scoping review on prioritisation activities for high consequence pathogens to map existing practice in this field beyond COVID-19.11 Conclusion From consultations on lessons learnt from research prioritisation during the COVID-19 pandemic, the GloPID-R Research in LMICs Working Group has identified key recommendations for developing and applying research priorities crucial for improving disease outbreak preparedness and response in the future. The remaining unknowns: a mixed methods study of the current and global health research priorities for covid-19.

关键词： SARS-CoV-2   brain stimulation   post-COVID-19   systematic review   transcranial electrical stimulation   transcutaneous vagus nerve stimulation  

摘要： Alongside the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, the number of patients with persistent symptoms following acute infection with SARS-CoV-2 is of concern. It is estimated that at least 65 million people worldwide meet criteria for what the World Health Organization (WHO) defines as "post-COVID-19 condition" - a multisystem disease comprising a wide range of symptoms. Effective treatments are lacking. In the present review, we aim to summarize the current evidence for the effectiveness of non-invasive or minimally invasive brain stimulation techniques in reducing symptoms of post-COVID-19. A total of nineteen studies were identified, one using transcutaneous vagus nerve stimulation (tVNS), another using transorbital alternating current stimulation (toACS), six studies on transcranial magnetic stimulation (TMS) and eleven studies on transcranial direct current stimulation (tDCS) for the treatment of post-COVID-19 symptoms. Existing studies report first promising results, illustrating improvement in clinical outcome parameters. Yet, the mechanistic understanding of post-COVID-19 and how brain stimulation techniques may be benefitial are limited. Directions for future research in the field are discussed.

关键词： Silver price volatility   Oil prices volatility   China stock exchange   Econometric model   EXCHANGE-RATE   GOLD PRICES   STOCK-MARKET   LINKAGES  

摘要： Several research studies globally focus on the volatility of gold and oil prices, neglecting an examination of silver price volatility in relation to other market commodities. The current Covid-19 pandemic has led to various uncertainties and fluctuations in financial and stock exchange markets, yet existing literature primarily concentrates on individual product rates rather than combined rate changes. Our study aims to bridge this research gap by analyzing the relationship between oil rates, silver rates, oil rate transitions, and silver rate transitions on the security exchange in China from 1990 to 2022, using the ARDL approach and Nonlinear ARDL for a comprehensive assessment. The findings reveal a significant impact of silver and oil rates on China's security exchange in the future, with the negative effects of oil rate changes and a positive effect of silver rate transitions. In the short term, oil and silver rates play a crucial role in influencing China's security exchange, highlighting the importance of monitoring these trends for investors. It is recommended that investors respond prudently to market transitions, particularly by considering silver as a secure option during times of uncertainty, while policymakers should implement appropriate measures to manage the rapid fluctuations from oil to the security market.

关键词： COVID-19   Catheter -related bloodstream infections   Gram-negative bacilli   Intensive care unit   PREVENTION   GUIDELINES   UNITS  

摘要： Introduction: The COVID-19 pandemic increased catheter-related bloodstream infections (C-RBSI), but its subsequent impact has not been adequately described. Our hospital has already depicted the effects of the COVID-19 pandemic in the first wave. However, we still do not know whether CRBSI rates and aetiology are similar to those described before the COVID-19 pandemic. We aimed to evaluate the impact of the COVID-19 pandemic on the evolution of C-RBSI in a large tertiary teaching hospital two years later. Material and methods: We prospectively collected all confirmed C-RBSI episodes in a clinical microbiology laboratory database by matching blood cultures and catheter tip cultures with the isolation of the same microorganism (s). We compared our C-RBSI incidence rates and aetiology from 2018 to 2023. C-RBSI was defined as bacteremia or fungemia in a patient with clinical manifestations of infection and no other apparent source except the catheter. Results: During the study period, we collected 556 C-RBSI episodes. C-RBSI incidence rate per 1000 admissions each year was as follows: 2018: 2.2; 2019: 1.7; 2020: 3.29; 2021: 2.92; 2022: 2.69. and 2023: 2.01. Mainly, C-RBSI episodes occurring in critical care units each year were, respectively: 2018: 57 (54.8 %), 2019: 38 (45.2 %), 2020: 89 (63.6 %), 2021: 69 (60.5 %), 2022: 58 (50.9 %) and 2023 (61.4 %). The distribution of microorganisms showed an increase in Gramnegative episodes after the pandemic. Conclusion: Our study shows an increase in the incidence rate of C-RBSI during the COVID-19 pandemic, with a discrete decrease after that. C-RBSI episodes were mainly caused by coagulase-negative Staphylococci but with a rise in Gram-negative bacilli.

关键词： COVID-19 pandemic   National emergency policy   Individualism   Collectivism   Democracy  

摘要： This study investigates the efficacy of national emergency response policies in addressing the COVID-19 pandemic and their interactions with cultural and political factors. Employing the synthetic control method, we analyze data from countries on five continents that implemented such policies in early 2020. Our results indicate the overall effectiveness of these policies in mitigating the impact of COVID-19 yet reveal significant variability in their outcomes among countries. Notably, we identify a negative association between policy effectiveness and a culture characterized by individualism. Additionally, we observe that the impact of COVID-19 response measures is more prominent in countries with lower levels of democracy. These findings offer valuable insights into the intricate interplay between COVID-19 response policies, cultural dynamics, and political regimes, with potential implications for future policy decisions and research endeavors.

关键词： Public health emergency   Implementation of criminal law   Risk assessment   Risk criminal law   China   COVID-19   SCIENCE  

摘要： This study addresses the complexities of applying criminal law during public health emergencies, particularly under the shadow of scientific uncertainty, and explores the challenge of balancing public health protection with individual rights. The primary aim is to dissect the application of criminal law in the context of the COVID-19 pandemic in China, focusing on the impact of scientific uncertainty on legal decision-making and the efficacy of criminal law interventions in public health crises. This study utilized a doctrinal method combined with case studies, integrating theoretical frameworks on risk and uncertainty with an analysis of China's legal responses to COVID-19. It involved assessing legislative and policy documents alongside judicial decisions, focusing on their alignment with evolving scientific understanding and public health strategies. The study reveals significant hurdles, including the limitations of empirical rules in judicial judgments, the emergence of technocratic bureaucracy, and the complexities surrounding risk mitigation and legal attribution under uncertain conditions. It highlights the inadequacy of traditional criminal law mechanisms to respond dynamically to the evolving landscape of public health emergencies. To address these challenges, the study recommends the development of temporary criminal legislation tailored to public health emergencies, the adoption of risk-based criminal law approaches, and the refinement of individualized risk assessment procedures. These measures aim to provide a more flexible and effective legal framework capable of safeguarding public health while ensuring the protection of individual liberties during crises.

关键词： Health care workers   Quality of life   Physical health   Mental health   COVID-19 protocols   Physical distancing   Hand hygiene   Personal protective equipments   PERSONAL PROTECTIVE EQUIPMENT   CARE WORKERS  

摘要： This study conducts an empirical retrospective examination of the effect of COVID-19 protocols on Health workers' quality of life during the pandemic. Data from a survey respondent of 330 health workers were analyzed through structural equation modeling. Results indicated COVID-19 protocols specifically hand hygiene, personal protective equipments, and physical distancing had a significant effect on the quality of life of health workers during the COVID-19 era. However, the results did not follow the expected literature trend. Analysis indicated a direct significant positive relationship between hand hygiene and quality of life and also highlighted a negative relationship between physical distancing and protective equipments and quality of life. Detailed analysis in an attempt to explain this development highlighted the significant role physical and mental health play in the relationship between COVID-19 safety protocols and quality of life. The findings of the study suggest implications and suggestions for future research.

关键词： SARS-CoV-2   COVID-19   Adaptive immunity   Cytokine storm   Immune memory   MESSENGER-RNA VACCINES   SARS-COV-2   ANTIBODY   BIOLOGY  

摘要： SARS-CoV-2 infection can trigger cytokine storm in some patients, which characterized by an excessive production of cytokines and chemical mediators. This hyperactive immune response may cause significant tissue damage and multiple organ failure (MOF). The severity of COVID-19 correlates with the intensity of cytokine storm, involving elements such as IFN, NF-kappa B, IL-6, HMGB1, etc. It is imperative to rapidly engage adaptive immunity to effectively control the disease progression. CD4+ T cells facilitate an immune response by improving B cells in the production of neutralizing antibodies and activating CD8+ T cells, which are instrumental in eradicating virus-infected cells. Meanwhile, antibodies from B cells can neutralize virus, obstructing further infection of host cells. In individuals who have recovered from the disease, virus-specific antibodies and memory T cells were observed, which could confer a level of protection, reducing the likelihood of re-infection or attenuating severity. This paper discussed the roles of macrophages, IFN, IL-6 and HMGB1 in cytokine release syndrome (CRS), the intricacies of adaptive immunity, and the persistence of immune memory, all of which are critical for the prevention and therapeutic strategies against COVID-19.