title: Banking for health: the role of financial sector actors in investing in global health

text: The world faces multiple health financing challenges as the global health burden evolves. Countries have set an ambitious health policy agenda for the next 15 years with prioritisation of universal health coverage under the Sustainable Development Goals. The scale of investment needed for equitable access to health services means global health is one of the key economic opportunities for decades to come. New financing partnerships with the private sector are vital. The aim of this study is to unlock additional financing sources, acknowledging the imperative to link financial returns to the providers of capital, and create profitable, sustainable financing structures. This paper outlines the global health investment opportunity exploring intersections of financial and health sector interests, and the role investment in health can play in economic development. Considering increasing demand for impact investments, the paper explores responsible financing initiatives and expansion of the global movement for sustainable capital markets. Adding an explicit health component (H) to the Environmental, Social and Governance (ESG) investment criteria, creating the ESG+H initiative, could serve as catalyst for the inclusion of health criteria into mainstream financial actors’ business practices and investment objectives. The conclusion finds that health considerations directly impact profitability of the firm and therefore should be incorporated into financial analysis. Positive assessment of health impact, at a broad societal or environmental level, as well as for a firm’s employees can become a value enhancing competitive advantage. An ESG+H framework could incorporate this into mainstream financial decision-making and into scalable investment products.


title: Aptamers in Diagnostics and Treatment of Viral Infections

text: Aptamers are in vitro selected DNA or RNA molecules that are capable of binding a wide range of nucleic and non-nucleic acid molecules with high affinity and specificity. They have been conducted through the process known as SELEX (Systematic Evolution of Ligands by Exponential Enrichment). It serves to reach specificity and considerable affinity to target molecules, including those of viral origin, both proteins and nucleic acids. Properties of aptamers allow detecting virus infected cells or viruses themselves and make them competitive to monoclonal antibodies. Specific aptamers can be used to interfere in each stage of the viral replication cycle and also inhibit its penetration into cells. Many current studies have reported possible application of aptamers as a treatment or diagnostic tool in viral infections, e.g., HIV (Human Immunodeficiency Virus), HBV (Hepatitis B Virus), HCV (Hepatitis C Virus), SARS (Severe Acute Respiratory Syndrome), H5N1 avian influenza and recently spread Ebola. This review presents current developments of using aptamers in the diagnostics and treatment of viral diseases.


Wellness in pediatric radiology: lessons learned in a time of pandemic


title: The Canadian Pandemic Influenza Plan: an evolution to the approach for national communicable disease emergencies

text: Abstract Advance planning for a large-scale and widespread health emergency is required to optimize health care delivery during an influenza pandemic. The Canadian Pandemic Influenza Plan (CPIP) is an example of a successful communicable disease emergency plan that ensures a national, coordinated approach to preparedness, response and recovery activities in the event of an influenza pandemic. The general concepts incorporated into the CPIP may be utilised in the contingency planning for a bioterrorism event or other communicable disease emergencies, including: a national, coordinated approach in planning; an emergency management structure to conduct the response; the use of common terminology to facilitate communication and response coordination, and the establishment of specific technical, communications and operational response groups and networks in advance. The multinational outbreak of Severe Acute Respiratory Syndrome (SARS) in 2003 offered the opportunity for the testing of these concepts. The experiences and lessons learnt during the SARS response may be utilised to strengthen communicable disease preparedness and response capacity.


title: After the COVID-19 pandemic: returning to normalcy or returning to a new normal?

text: Abstract The novel coronavirus, SARS-CoV-2, pandemic has delivered a profound and negative impact on the United States. The suspension of elective surgeries including arthroplasty will have a lasting effect on all stakeholders including patients, physicians, and healthcare organizations within the US healthcare system. Resumption of elective hip and knee arthroplasty will need to be carefully focused. The purpose of this work is to address potential strategies, concerns, and regulatory barriers in restarting elective hip and knee arthroplasty in the US.


title: Enteric viruses in HIV-related diarrhoea

text: Abstract HIV-related diarrhoea is an important cause of morbidity and mortality in HIV infection. Cytomegalovirus is a well-established cause of diarrhoea, but the role of other enteric viruses is less clear and will be discussed here. The clinical manifestations, disease mechanisms, diagnostic techniques and current treatments for the management of these infections are reviewed.


title: An emergency responding mechanism for cruise epidemic prevention—taking COVID-19 as an example

text: COVID-19 has severely impacted the global cruise tourism industry. The increasing number of confirmed cases during the quarantine period of ‘Diamond Princess’ questioned the efficiency and science behind the Japanese government's emergency management of the outbreak and led to a debate on the responsibilities of the ship's country of registry and port country. In order to deal with the spread of virus on a cruise ship rationally, the present study analyses why cruise ships are more prone to an emergent epidemic and discusses requirements of international conventions and domestic laws on cruise ship sanitation and epidemic prevention. It also evaluates the rescue responsibility of Flag State and Port State, explores the legal lacunae of international conventions on the rescue obligation of cruise home port, and provides solutions for prevention and control of cruise ship epidemic with short-term response measures and long-term mechanism construction. In terms of a short-term response, it is vital to adopt the quarantine idea of a ‘temporary cabin hospital’ and a disposal procedure of ‘circular disinfection-section repeat testing-batch transfer and quarantine-international collaborative medical treatment’. For a long-term mechanism construction, three aspects need to be considered: the risk emergency management mechanism of cruise lines, health and epidemic prevention supervision mechanisms, and international cooperation mechanisms of infectious disease prevention.


Some lessons from the COVID‐19 pandemic


title: Richard Allen Williams, M.D.: a Career Fighting Disparities and Fostering Equity

text: This is a literature review where we acknowledge Richard Allen Williams, the first African American physician to win the John P. McGovern Compleat Physician Award, and recognize his achievements in race and ethnicity in healthcare. There have been significant advances in the diagnosis and treatment of cardiovascular disease; however, racial disparities continue to create inequity in the medical community especially for African Americans. Dr. Williams founded the Association of Black Cardiologists (ABC) in 1974 to address the misperception about, and the misdiagnosis and maltreatment of African American patients. He emphasized the importance of diversity and the non-biased approach to the treatment of all communities. This literary review further explores current racial disparities African Americans face during the COVID-19 pandemic. Granted that Dr. Williams’ win is a step towards progress and change, there is much to be done to conquer the cultural divide in healthcare.


title: Chapter 9 Diverse Roles of DEAD/DEAH-Box Helicases in Innate Immunity and Diseases

text: Abstract DEAD/DEAH-box helicases are enzymes that belong to the DEAD/H-box family of SF2 helicase superfamily. These enzymes are essential in RNA metabolism, where they are involved in a number of processes that require manipulation of RNA structure. Recent studies have found that some DEAD/DEAH-box helicases play important roles in innate immunity, where they act as sensors of cytosolic DNA/RNA, as adaptor proteins, or as regulators of signaling and gene expression. In spite of their function in immunity, DEAD/DEAH-box helicases can also be hijacked and exploited by viruses to circumvent detection and aid in viral replication. These findings not only imply that DEAD/DEAH-box helicases have a broader function than previously thought, but also give us a much better understanding of immune mechanisms and diseases that arise due to the dysregulation or evasion thereof. In this chapter, we demonstrate the known scope of activities of human DEAD/DEAH-box helicases in innate immunity and interaction with viruses or other pathogens. Additionally, we give an outline of diseases in which they are, or may be, involved in the context of immunity.


title: Experience of establishing severe acute respiratory surveillance in the Netherlands: evaluation and challenges

text: Abstract The 2009 influenza A(H1N1) pandemic prompted the World Health Organization (WHO) to recommend countries to establish a national severe acute respiratory infections (SARI) surveillance system for preparedness and emergency response. However, setting up or maintaining a robust SARI surveillance system has been challenging. Similar to other countries, surveillance data on hospitalisations for SARI in the Netherlands are still limited, in contrast to the robust surveillance data in primary care. The objective of this narrative review is to provide an overview, evaluation, and challenges of already available surveillance systems or datasets in the Netherlands, which might be used for near real-time surveillance of severe respiratory infections. Seven available surveillance systems or datasets in the Netherlands were reviewed. The evaluation criteria, including data quality, timeliness, representativeness, simplicity, flexibility, acceptability and stability were based on United States Centers for Disease Control and Prevention (CDC) and European Centre for Disease Prevention and Control (ECDC) guidelines for public health surveillance. We added sustainability as additional evaluation criterion. The best evaluated surveillance system or dataset currently available for SARI surveillance is crude mortality monitoring, although it lacks specificity. In contrast to influenza-like illness (ILI) in primary care, there is currently no gold standard for SARI surveillance in the Netherlands. Based on our experience with sentinel SARI surveillance, a fully or semi-automated, passive surveillance system seems most suited for a sustainable SARI surveillance system. An important future challenge remains integrating SARI surveillance into existing hospital programs in order to make surveillance data valuable for public health, as well as hospital quality of care management and individual patient care.


title: Emerging viral diseases in kidney transplant recipients

text: Viruses are the most important cause of infections and a major source of mortality in Kidney Transplant Recipients (KTRs). These patients may acquire viral infections through exogenous routes including community exposure, donor organs, and blood products or by endogenous reactivation of latent viruses. Beside major opportunistic infections due to CMV and EBV and viral hepatitis B and C, several viral diseases have recently emerged in KTRs. New medical practices or technologies, implementation of new diagnostic tools, and improved medical information have contributed to the emergence of these viral diseases in this special population. The purpose of this review is to summarize the current knowledge on emerging viral diseases and newly discovered viruses in KTRs over the last two decades. We identified viruses in the field of KT that had shown the greatest increase in numbers of citations in the NCBI PubMed database. BKV was the most cited in the literature and linked to an emerging disease that represents a great clinical concern in KTRs. HHV‐8, PVB19, WNV, JCV, H1N1 influenza virus A, HEV, and GB virus were the main other emerging viruses. Excluding HHV8, newly discovered viruses have been infrequently linked to clinical diseases in KTRs. Nonetheless, pathogenicity can emerge long after the discovery of the causative agent, as has been the case for BKV. Overall, antiviral treatments are very limited, and reducing immunosuppressive therapy remains the cornerstone of management. Copyright © 2012 John Wiley & Sons, Ltd.


title: Chapter 19 Advantages and Limitations of Commonly Used Nonhuman Primate Species in Research and Development of Biopharmaceuticals

text: Abstract Nonhuman primates (NHPs) have been used extensively during the past four decades for research and nonclinical development because they are close to humans in terms of genetics, anatomy, physiology, and immunology. They have been widely used in the development of infection models, leading to the generation of vaccines and drugs, as well as in the nonclinical pharmacologic and toxicologic assessment of biopharmaceuticals, especially in the fields of immunotherapy and oncology, despite the constant pressure to move to lower species. In many cases, NHPs are the only species that allows a correct risk assessment for humans. Nevertheless, limitations inherent to each species have to be considered before an investigation. This chapter shines some light on the respective interests and limitations of using cynomolgus monkeys, rhesus monkeys, and marmosets in medical research and nonclinical development, with a specific focus on reproduction and immunology.


title: Human immunodeficiency virus infection (HIV)–associated rheumatic manifestations in thepre- and post-HAART eras

text: Rheumatic manifestations remain an important clinical manifestation associated to HIV. To date after 4 decades of the onset of the HIV/AIDS pandemic, almost 37 million individuals are living with the infection, including close to 2 million of newly infected individuals. The status, however, of a considerable proportion of HIV/AIDS patients has changed from a near fatal disorder secondary to opportunistic infections to a chronic disease in which renal cardiovascular, diabetes, malignancy, and autoimmune co-morbid disorders have become prevalent and relevant. In addition, the spectrum of rheumatic disorders also has changed since the introduction of HAART and its diagnosis and treatment represents a challenge. The purpose of this review is to define and discuss the HIV-related rheumatic manifestations in the pre- and post-HAART eras.


title: The effect of respiratory viral assay panel on antibiotic prescription patterns at discharge in adults admitted with mild to moderate acute exacerbation of COPD: a retrospective before- after study

text: BACKGROUND: Despite well-defined criteria for use of antibiotics in patients presenting with mild to moderate Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD), their overuse is widespread. We hypothesized that following implementation of a molecular multiplex respiratory viral panel (RVP), AECOPD patients with viral infections would be more easily identified, limiting antibiotic use in this population. The primary objective of our study was to investigate if availability of the RVP decreased antibiotic prescription at discharge among patients with AECOPD. METHODS: This is a single center, retrospective, before (pre-RVP) - after (post-RVP) study of patients admitted to a tertiary medical center from January 2013 to March 2016. The primary outcome was antibiotic prescription at discharge. Groups were compared using univariable and multivariable logistic-regression. RESULTS: A total of 232 patient-episodes were identified, 133 following RVP introduction. Mean age was 68.1 (pre-RVP) and 68.3 (post-RVP) years respectively (p = 0.88). Patients in pre-RVP group were similar to the post-RVP group with respect to gender (p = 0.54), proportion of patients with BMI < 21(p = 0.23), positive smoking status (p = 0.19) and diagnoses of obstructive sleep apnea (OSA, p = 0.16). We found a significant reduction in antibiotic prescription rate at discharge in patients admitted with AECOPD after introduction of the respiratory viral assay (pre-RVP 77.8% vs. post-RVP 63.2%, p = 0.01). In adjusted analyses, patients in the pre-RVP group [OR 2.11 (CI: 1.13–3.96), p = 0.019] with positive gram stain in sputum [OR 4.02 (CI: 1.61–10.06), p = 0.003] had the highest odds of antibiotic prescription at discharge. CONCLUSIONS: In patients presenting with mild to moderate Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD), utilization of a comprehensive respiratory viral panel can significantly decrease the rate of antibiotic prescription at discharge.


title: Linking Human Destruction of Nature to COVID-19 Increases Support for Wildlife Conservation Policies

text: This paper investigates if narratives varying the cause of the COVID-19 pandemic affects pro-wildlife conservation outcomes. In a pre-registered online experiment (N = 1081), we randomly allocated subjects to either a control group or to one of three narrative treatment groups, each presenting a different likely cause of the COVID-19 outbreak: an animal cause; an animal and human cause (AHC); and an animal, human or lab cause. We found that the AHC narrative elicited significantly greater pro-conservation policy support, especially for bans in the commercial trade of wildlife, when compared to the control group. Possible mechanisms driving this effect are that AHC narratives were less familiar, elicited higher mental and emotional engagement, and induced feelings that firms and governments are responsible for mitigating wildlife extinction.


title: Expression of Single Chain Variable Fragment (scFv) Molecules in Plants: A Comprehensive Update

text: Single chain variable fragments (scFvs) are generated by joining together the variable heavy and light chain of a monoclonal antibody (mAb) via a peptide linker. They offer some advantages over the parental mAb such as low molecular weight, heterologous production, multimeric form, and multivalency. The scFvs were produced against more than 50 antigens till date using 10 different plant species as the expression system. There were considerable improvements in the expression and purification strategies of scFv in the last 24 years. With the growing demand of scFv in therapeutic and diagnostic fields, its biosynthesis needs to be increased. The easiness in development, maintenance, and multiplication of transgenic plants make them an attractive expression platform for scFv production. The review intends to provide comprehensive information about the use of plant expression system to produce scFv. The developments, advantages, pitfalls, and possible prospects of improvement for the exploitation of plants in the industrial level are discussed.


title: Integrating the preventive medicine specialty in the rural and public health workforce

text: Abstract The majority of the U.S. American Indian and Alaska Native (AI/AN) population live in rural areas, and are thus disproportionately affected by rural health issues. In addition, the AI/AN population has unique health characteristics resulting from a distinct cultural and sociopolitical history. A public health approach to both rural and Tribal health should include the medical specialty of preventive medicine, a unique physician specialty that combines both direct patient care and public health skills. To best prepare preventive medicine physicians for rural and Tribal practice, medical schools could recruit students from rural and Tribal areas and encourage them to pursue the specialty of preventive medicine. Additionally, preventive medicine residency training programs could establish clinical and public health practicum rotations in rural and Tribal areas, and develop curricula that address rural and Tribal health issues. Currently very few preventive medicine residency programs expressly state a mission to train physicians in rural or Tribal settings.


title: Mouse hepatitis virus nasoencephalopathy is dependent upon virus strain and host genotype

text: Mouse hepatitis virus (MHV) S induced typical MHV spongiform lesions in brainstem 28 days following intranasal inoculation of adult A/J, BALB/cByJ, CBA/J, C3H/HeJ and C3H/RV, but not SJL mice. In all but SJL mice, brain lesions occurred at or near the infectious dose level, based on seroconversion by the indirect immunofluorescence assay. During the acute phase of infection (day 5), lesions were limited to the nose and brain in most genotypes. Exceptions were BALB mice, which had mild hepatitis and SJL mice, which had lesions restricted to the nose. No mortality occurred in any genotype. Following intranasal inoculation of adult mice, MHV-1, -3, -A 59,-JHM and -S all caused brain lesions at 28 days after inoculation. MHV-1 and-3 caused lesions that were usually restricted to the anterior olfactory tracts, while MHV-A 59, -S and -JHM also caused more generalized and pronounced lesions involving the midbrain and pons. These studies suggest that avirulent MHV-S given intranasally to most mouse genotypes is a good model for induction of brain infection in the absence of mortality. They also confirm observations made by others in which MHV-JHM, -S and -A 59 are relatively more neurotropic than other MHV strains, such as MHV-1 and -3.


title: Análisis de las tasas de letalidad de la infección por SARS-CoV-2 en las Comunidades Autónomas de España

text: Resumen Introducción: La pandemia por el virus SARS-CoV-2 ha supuesto un auténtico reto para los sistemas sanitarios. En España, la distribución heterogénea del virus y las diferentes estrategias sanitarias han condicionado la morbilidad y letalidad. El objetivo de este estudio fue analizar la letalidad de la infección por sexo y rangos de edad en las CCAA de España. Material y métodos: Para realizar el análisis, los datos se extrajeron del Ministerio de Sanidad, Consejerías y departamentos de Salud Pública de las diferentes CCAA. Se estimó la población infectada a partir de los resultados del ENE-COVID19 y de la población censada a 1 de enero de 2020 (INE) para una validez del test de anticuerpos IgG con 80% de sensibilidad y 100% de especificidad. La tasa de letalidad (TL) (fallecidos/1000 infectados estimados) por sexo y edad (<20 años, 20-64 y ≥65 años) se calculó para cada CCAA. Se calculó la razón estandarizada de letalidad (REL) por el método exacto (EPIDAT). Resultados: La prevalencia estimada de infección por SARS-CoV-2 en España fue del 6 % (rango, 1,4% Ceuta - 14,1% Comunidad de Madrid). La TL para el conjunto de España fue del 9,6/1000 oscilando entre el 1/1000 en Melilla y 26,6/1000 en La Rioja, sin que se encontrara correlación entre letalidad y prevalencia de la infección. La TL fue mayor en hombres (10,2/1000, razón 1,17 respecto de mujeres) excepto en Cataluña (razón 0,92) y especialmente elevada en los mayores de 64 años en La Rioja (143,5/1000), Asturias (69,2/1000) y País Vasco (46,6/1000). Se encontró un exceso de letalidad (REL) global superior al 30% en La Rioja (2,91; IC 95% 2,36-3,57), Asturias (1,51; IC 95% 1,27-1,80), País Vasco (1,42; IC 95% 1,31-1,54) y Extremadura (1,37; IC 95% 1,20-1,57) y en los mayores de 64 años en Madrid y Canarias. Conclusiones: La infección por el virus SARs-Cov-2 se ha distribuido de forma muy irregular en las diferentes CC.AA., existiendo una gran diferencia en la tasa de letalidad entre Comunidades, siendo especialmente elevada en La Rioja, Asturias y País Vasco. Es relevante el exceso de letalidad respecto a la media nacional en la población mayor de 64 años en las CCAA de Madrid y Canarias. Summary Introduction: The SARS-CoV-2 pandemic has posed a real challenge to health systems. In Spain, the heterogeneous distribution of the virus infection and the different health strategies have conditioned the morbidity and fatality rate. The aim of this study was to analyse the lethality of the infection by sex and age range in the Autonomous Communities (AC) of Spain. Material and methods. To perform the analysis, data were extracted from the Ministry of Health, Regional and Public Health Departments of the different AC. The infected population was estimated from the results of the ENE-COVID19 and the population registered on 1 January 2020 (INE) for the validity of the IgG antibody test with 80% sensitivity and 100% specificity. The case fatality rate (TL) (deaths/1000 estimated infected) by sex and age (<20 years, 20-64 and ≥65 years) was calculated for each AC. The standardized case fatality ratio (REL) was calculated by the exact method (EPIDAT). Results. The estimated prevalence of SARS-CoV-2 infection in Spain was 6% (range, 1.4% Ceuta - 14.1% Community of Madrid). The TL in Spain was 9,6/1000, ranged per AC from 1/1000 in Melilla to 26.6/1000 in La Rioja, with no correlation between case fatality and prevalence of infection. The TL was higher in men (10.2/1000, ratio 1.17 with respect to women) except in Cataluña (ratio 0.92) and especially high in those over 64 years of age in La Rioja (143.5/1000), Asturias (69.2/1000) and Basque Country (46.6/1000). Overall excess REL was found to be over 30% in La Rioja (2.91, 95% CI 2.36-3.57), Asturias (1.51, 95% CI 1.27-1.80), Basque Country (1.42, 95% CI 1.31-1.54) and Extremadura (1.37, 95% CI 1.20-1.57) and in those over 64 years in Madrid and the Canary Islands. Conclusions: SARs-Cov-2 virus infection has been very unevenly distributed in the different ACs, with notably differences in TL between ACs, particularly high in La Rioja, Asturias and the Basque Country. Ir important to study the excess in TL the population over 64 years of age in the Autonomous Regions of Madrid and the Canary Islands.


title: Travel-related MERS-CoV cases: an assessment of exposures and risk factors in a group of Dutch travellers returning from the Kingdom of Saudi Arabia, May 2014

text: BACKGROUND: In May 2014, Middle East respiratory syndrome coronavirus (MERS-CoV) infection, with closely related viral genomes, was diagnosed in two Dutch residents, returning from a pilgrimage to Medina and Mecca, Kingdom of Saudi Arabia (KSA). These patients travelled with a group of 29 other Dutch travellers. We conducted an epidemiological assessment of the travel group to identify likely source(s) of infection and presence of potential risk factors. METHODS: All travellers, including the two cases, completed a questionnaire focussing on potential human, animal and food exposures to MERS-CoV. The questionnaire was modified from the WHO MERS-CoV questionnaire, taking into account the specific route and activities of the travel group. RESULTS: Twelve non-cases drank unpasteurized camel milk and had contact with camels. Most travellers, including one of the two patients (Case 1), visited local markets, where six of them consumed fruits. Two travellers, including Case 1, were exposed to coughing patients when visiting a hospital in Medina. Four travellers, including Case 1, visited two hospitals in Mecca. All travellers had been in contact with Case 1 while he was sick, with initially non-respiratory complaints. The cases were found to be older than the other travellers and both had co-morbidities. CONCLUSIONS: This epidemiological study revealed the complexity of MERS-CoV outbreak investigations with multiple potential exposures to MERS-CoV reported such as healthcare visits, camel exposure, and exposure to untreated food products. Exposure to MERS-CoV during a hospital visit is considered a likely source of infection for Case 1 but not for Case 2. For Case 2, the most likely source could not be determined. Exposure to MERS-CoV via direct contact with animals or dairy products seems unlikely for the two Dutch cases. Furthermore, exposure to a common but still unidentified source cannot be ruled out. More comprehensive research into sources of infection in the Arabian Peninsula is needed to strengthen and specify the prevention of MERS-CoV infections.


title: Slum Livestock Agriculture

text: Abstract Slums are unplanned squatter human settlements in peri-urban and urban areas where more than 800 million people live. These densely populated areas lack basic public services. Livestock raised in these conditions compete with humans for space and water, and pose a risk to human and animal health. Notwithstanding the risk of disease transmission, slum livestock agriculture plays an essential role in the livelihoods of people and deserves consideration in urban planning and policy making.


title: Comment on “The neuroinvasive potential of SARS‐CoV‐2 may play a role in the respiratory failure of COVID‐19 patients”

text: We have read with great care and interest the article by Li et al The authors provide interesting elements with respect to the possible entry of severe acute respiratory syndrome coronavirus 2 at the brain area and plead for an implication of the central nervous system in respiratory problems linked to coronavirus disease. Here we provide additional elements that support those observations, notably the role of brainstem structures located in the medulla oblongata in modulating respiration. We also discussed the possible pathways the virus uses to cross the brain blood barrier and reach the brainstem.


title: Modelling SARS-COV2 Spread in London: Approaches to Lift the Lockdown

text: Abstract Objective To use mathematical models to predict the epidemiological impact of lifting the lockdown in London, UK, and alternative strategies to help inform policy in the UK. Methods A mathematical model for the transmission of SARS-CoV2 in London. The model was parametrised using data on notified cases, deaths, contacts, and mobility to analyse the epidemic in the UK capital. We investigated the impact of multiple non pharmaceutical interventions (NPIs) and combinations of these measures on future incidence of COVID-19. Results Immediate action at the early stages of an epidemic in the affected districts would have tackled spread. While an extended lockdown is highly effective, other measures such as shielding older populations, universal testing and facemasks can all potentially contribute to a reduction of infections and deaths. However, based on current evidence it seems unlikely they will be as effective as continued lockdown. In order to achieve elimination and lift lockdown within 5 months, the best strategy seems to be a combination of weekly universal testing, contact tracing and use of facemasks, with concurrent lockdown. This approach could potentially reduce deaths by 48% compared with continued lockdown alone. Conclusions A combination of NPIs such as universal testing, contact tracing and mask use while under lockdown would be associated with least deaths and infections. This approach would require high uptake and sustained local effort but it is potentially feasible as may lead to elimination in a relatively short time scale.


title: Chapter 496 Arterivirus Papain-like Proteinase 1β

text: The third edition of the Handbook of Proteolytic Enzymes aims to be a comprehensive reference work for the enzymes that cleave proteins and peptides, and contains over 800 chapters. Each chapter is organized into sections describing the name and history, activity and specificity, structural chemistry, preparation, biological aspects, and distinguishing features for a specific peptidase. The subject of Chapter 499 is Arterivirus Papain-like Proteinase β. Keywords: Arterivirus, autoproteolytic proteinase release, cytoplasm-to-nucleus transport, innate immunity control, multidomain proteinase, multifunctional proteinase, polyprotein processing, RNA virus, single-cleavage proteinase, transcriptional control, virion formation control.


title: Dual Analysis of the Murine Cytomegalovirus and Host Cell Transcriptomes Reveal New Aspects of the Virus-Host Cell Interface

text: Major gaps in our knowledge of pathogen genes and how these gene products interact with host gene products to cause disease represent a major obstacle to progress in vaccine and antiviral drug development for the herpesviruses. To begin to bridge these gaps, we conducted a dual analysis of Murine Cytomegalovirus (MCMV) and host cell transcriptomes during lytic infection. We analyzed the MCMV transcriptome during lytic infection using both classical cDNA cloning and sequencing of viral transcripts and next generation sequencing of transcripts (RNA-Seq). We also investigated the host transcriptome using RNA-Seq combined with differential gene expression analysis, biological pathway analysis, and gene ontology analysis. We identify numerous novel spliced and unspliced transcripts of MCMV. Unexpectedly, the most abundantly transcribed viral genes are of unknown function. We found that the most abundant viral transcript, recently identified as a noncoding RNA regulating cellular microRNAs, also codes for a novel protein. To our knowledge, this is the first viral transcript that functions both as a noncoding RNA and an mRNA. We also report that lytic infection elicits a profound cellular response in fibroblasts. Highly upregulated and induced host genes included those involved in inflammation and immunity, but also many unexpected transcription factors and host genes related to development and differentiation. Many top downregulated and repressed genes are associated with functions whose roles in infection are obscure, including host long intergenic noncoding RNAs, antisense RNAs or small nucleolar RNAs. Correspondingly, many differentially expressed genes cluster in biological pathways that may shed new light on cytomegalovirus pathogenesis. Together, these findings provide new insights into the molecular warfare at the virus-host interface and suggest new areas of research to advance the understanding and treatment of cytomegalovirus-associated diseases.


title: Talk COVID to Me: Language Rights and Canadian Government Responses to the Pandemic

text: Since the COVID-19 outbreak, a gradual loosening of linguistic obligations in public institutions and governments has been observed in various jurisdictions in Canada. This article argues that in addition to legal requirements to provide minority language services, it is not justifiable for governments to suspend or curtail such services in an emergency situation, for reasons pertaining to public safety and public health. After performing a survey and analysis of government actions against their constitutional, legislative, and policy language obligations to highlight best practices and deficiencies, we discuss the policy implications of these actions. In conclusion, the article considers how governments could better uphold their language obligations in times of emergency.


title: Using machine learning to predict ICU transfer in hospitalized COVID-19 patients

text: Objectives: Approximately 20–30% of patients with COVID-19 require hospitalization, and 5–12% may require critical care in an intensive care unit (ICU). A rapid surge in cases of severe COVID-19 will lead to a corresponding surge in demand for ICU care. Because of constraints on resources, frontline healthcare workers may be unable to provide the frequent monitoring and assessment required for all patients at high risk of clinical deterioration. We developed a machine learning-based risk prioritization tool that predicts ICU transfer within 24 h, seeking to facilitate efficient use of care providers’ efforts and help hospitals plan their flow of operations. Methods: A retrospective cohort was comprised of non-ICU COVID-19 admissions at a large acute care health system between 26 February and 18 April 2020. Time series data, including vital signs, nursing assessments, laboratory data, and electrocardiograms, were used as input variables for training a random forest (RF) model. The cohort was randomly split (70:30) into training and test sets. The RF model was trained using 10-fold cross-validation on the training set, and its predictive performance on the test set was then evaluated. Results: The cohort consisted of 1987 unique patients diagnosed with COVID-19 and admitted to non-ICU units of the hospital. The median time to ICU transfer was 2.45 days from the time of admission. Compared to actual admissions, the tool had 72.8% (95% CI: 63.2–81.1%) sensitivity, 76.3% (95% CI: 74.7–77.9%) specificity, 76.2% (95% CI: 74.6–77.7%) accuracy, and 79.9% (95% CI: 75.2–84.6%) area under the receiver operating characteristics curve. Conclusions: A ML-based prediction model can be used as a screening tool to identify patients at risk of imminent ICU transfer within 24 h. This tool could improve the management of hospital resources and patientthroughput planning, thus delivering more effective care to patients hospitalized with COVID-19.


title: Molecular Targets in the Chemotherapy of Coronavirus Infection

text: In the pathogenesis of the infectious process in the respiratory tract by SARS, MERS, and COVID-19 coronaviruses, two stages can be distinguished: early (etiotropic) and late (pathogenetic) ones. In the first stage, when the virus multiplication and accumulation are prevalent under insufficient host immune response, the use of chemotherapeutic agents blocking the reproduction of the virus is reasonable to suppress the development of the disease. This article considers six major chemotherapeutic classes aimed at certain viral targets: inhibitors of viral RNA polymerase, inhibitors of viral protease Mpro, inhibitors of proteolytic activation of viral protein S allowing virus entry into the target cell, inhibitors of virus uncoating in cellular endosomes, compounds of exogenous interferons, and compounds of natural and recombinant virus-neutralizing antibodies. In the second stage, when the multiplication of the virus decreases and threatening pathological processes of excessive inflammation, acute respiratory distress syndrome, pulmonary edema, hypoxia, and secondary bacterial pneumonia and sepsis events develop, a pathogenetic therapeutic approach including extracorporeal blood oxygenation, detoxification, and anti-inflammatory and anti-bacterial therapy seems to be the most effective way for the patient’s recovery.


title: Transmission and Effect of Multiple Clusters of Seasonal Influenza in a Swiss Geriatric Hospital

text: OBJECTIVES: To investigate a nosocomial outbreak of influenza. DESIGN: Prospective outbreak investigation with active case finding and molecular typing. SETTING: A large academic geriatric hospital in Switzerland. PARTICIPANTS: Elderly hospitalized adults. MEASUREMENTS: Based on syndromic surveillance, a nosocomial influenza outbreak was suspected in February 2012. All suspected cases were screened for respiratory viruses using real‐time reverse transcription polymerase chain reaction of nasopharyngeal swabs. Infection control procedures (droplet precautions with single room isolation whenever possible) were implemented for all suspected or confirmed cases. Specimens positive for influenza viruses were processed and sequenced whenever possible to track transmission dynamics. RESULTS: Respiratory samples from 155 suspected cases were analyzed during the outbreak period, of which 69 (44%) were positive for influenza virus, 26 (17%) were positive for other respiratory viruses, and 60 (39%) were negative. Three other cases fulfilled clinical criteria for influenza infection but were not sampled, and one individual was admitted with an already positive test, resulting in a total of 73 influenza cases, of which 62 (85%) were classified as nosocomial. Five distinct clusters of nosocomial transmission were identified using viral sequencing, with epidemiologically unexpected in‐hospital transmission dynamics. Seven of 23 patients who experienced influenza complications died. Sixteen healthcare workers experienced an influenza‐like illness (overall vaccination rate, 36%). CONCLUSION: Nosocomial influenza transmission caused more secondary cases than repeated community importation during this polyclonal outbreak. Molecular tools revealed complex transmission dynamics. Low healthcare worker vaccination rates and gaps in recommended infection control procedures are likely to have contributed to nosocomial spread of influenza, which remains a potentially life‐threatening disease in elderly adults.


title: High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study

text: PURPOSE: Little evidence of increased thrombotic risk is available in COVID-19 patients. Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection. METHODS: All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included. Medical history, symptoms, biological data and imaging were prospectively collected. Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients. RESULTS: 150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points). Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting. Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO. Most patients (> 95%) had elevated D-dimer and fibrinogen. No patient developed disseminated intravascular coagulation. Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant. Comparison with non-COVID-19 ARDS patients (n = 145) confirmed that COVID-19 ARDS patients (n = 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs. 2.1%, p < 0.008). Coagulation parameters significantly differed between the two groups. CONCLUSION: Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications. Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-06062-x) contains supplementary material, which is available to authorized users.


title: Epidemieën zijn moeilijk beheersbaar

text: Halverwege de vorige eeuw had men een groot vertrouwen in de beheersbaarheid van infectieziekten. Maar nu, veertig jaar later, is het optimisme omgeslagen in bezorgdheid voor de toekomst. Hoe terecht is dat? In dit inleidend hoofdstuk wordt kort ingegaan op begrippen als ‘uitbraak’ en zoönose, de historie van pestilentieën, de risicofactoren en de manier waarop risicofactoren zouden kunnen worden aangepakt. Ziekten als pest, pokken en mazelen worden genoemd als voorbeeld van pestilentieën die min of meer onder controle zijn gebracht, en dengue als opkomende ziekte waartegen nog geen passend antwoord is gevonden.


title: Risk, resilience, psychological distress, and anxiety at the beginning of the COVID‐19 pandemic in Germany

text: BACKGROUND: The current COVID‐19 pandemic comes with multiple psychological stressors due to health‐related, social, economic, and individual consequences and may cause psychological distress. The aim of this study was to screen the population in Germany for negative impact on mental health in the current COVID‐19 pandemic and to analyze possible risk and protective factors. METHODS: A total of 6,509 people took part in an online survey in Germany from 27 March to 6 April. The questionnaire included demographic information and ascertained psychological distress, anxiety and depressive symptoms, and risk and protective factors. RESULTS: In our sample, over 50% expressed suffering from anxiety and psychological distress regarding the COVID‐19 pandemic. Participants spent several hours per day thinking about COVID‐19 (M = 4.45). Psychological and social determinants showed stronger associations with anxiety regarding COVID‐19 than experiences with the disease. CONCLUSIONS: The current COVID‐19 pandemic does cause psychological distress, anxiety, and depression for large proportions of the general population. Strategies such as maintaining a healthy lifestyle and social contacts, acceptance of anxiety and negative emotions, fostering self‐efficacy, and information on where to get medical treatment if needed, seem of help, while substance abuse and suppression of anxiety and negative emotions seem to be associated with more psychological burden.


title: Electron microscopy of stool‐shed viruses: Retention of characteristic morphologies after long‐term storage at ultralow temperatures

text: Storage of stool specimens at —70°C has been reported to destroy the characteristic morphology of calicivirus. To determine if other stool‐shed viruses are similarly affected, stool specimens previously examined by electron microscopy and observed to contain virus particles were reexamined after 6–10 years of storage at —70°C to —85°C. The stools contained virus particles of different morphological types, including astrovirus, small round structured virus, adenovirus, and rotavirus as well as calicivirus. Also reexamined were stools containing coronavirus‐like particles and T = 19 virus‐like particles. Characteristic virus particles, including calicivirus particles, were recognized in all the stools reexamined. The results indicate that long‐term storage of stools at ultralow temperatures does not present a significant problem for the morphological identification of stool‐shed viruses.


title: Exposure to greenspaces could reduce the high global burden of pain

text: Abstract Painful conditions are among the leading causes of years lived with disability. To reduce this burden, novel, cost-effective and accessible interventions are required. We propose that greenspace exposure may be one such intervention. Drawing on evidence from neuroscience, physiology, microbiology, and psychology, we articulate how and why exposure to greenspaces could improve pain outcomes and reduce the high global burden of pain. Greenspace exposure potentially provides opportunities to benefit from known or proposed health-enhancing components of nature, such as environmental microbiomes, phytoncides, negative air ions, sunlight, and the sights and sounds of nature itself. We review the established and potential links between these specific exposures and pain outcomes. While further research is required to determine possible causal links between greenspace exposure and pain outcomes, we suggest that there is already sufficient evidence to help reduce the global burden of pain by improving access and exposure to quality greenspaces.


title: Safety and efficacy assessment of allogeneic human dental pulp stem cells to treat patients with severe COVID-19: structured summary of a study protocol for a randomized controlled trial (Phase I / II)

text: OBJECTIVES: To assess the safety and therapeutic effects of allogeneic human dental pulp stem cells (DPSCs) in treating severe pneumonia caused by COVID-19. TRIAL DESIGN: This is a single centre, two arm ratio 1:1, triple blinded, randomized, placebo-controlled, parallel group, clinical trial. PARTICIPANTS: 1. Adults aged 18-65 years; 2. Voluntarily participate in this clinical trial and sign the “informed consent form” or have consent from a legal representative. 3. Diagnosed with severe pneumonia of COVID-19: nucleic acid test SARS-CoV-2 positive; respiratory distress (respiratory rate > 30 times / min); hypoxia (resting oxygen saturation < 93% or arterial partial pressure of oxygen / oxygen concentration < 300 mmHg). 4. COVID-19 featured lung lesions in chest X-ray image. 1. Patients have received other experimental treatment for COVID-19 within the last 30 days; 2. Patients have severe liver condition (e.g., Child Pugh score >=C or AST> 5 times of the upper limit); 3. Patients with severe renal insufficiency (estimated glomerular filtration rate <=30mL / min/1.73 m(2)) or patients receiving continuous renal replacement therapy, hemodialysis, peritoneal dialysis; 4. Patients who are co-infected with HIV, hepatitis B, tuberculosis, influenza virus, adenovirus or other respiratory infection viruses; 5. Female patients who have no sexual protection in the last 30 days prior to the screening assessment; 6. Pregnant or lactating women or women using estrogen contraception; 7. Patients who are planning to become pregnant during the study period or within 6 months after the end of the study period; 8. Other conditions that the researchers consider not suitable for participating in this clinical trial. INTERVENTION AND COMPARATOR: There will be two study groups: experimental and control. Both will receive all necessary routine treatment for COVID-19. The experimental group will receive an intravenous injection of dental pulp stem cells suspension (3.0x10(7) human DPSCs in 30ml saline solution) on day 1, 4 and 7; The control group will receive an equal amount of saline (placebo) on the same days. Clinical and laboratory observations will be performed for analysis during a period of 28 days for each case since the commencement of the study. MAIN OUTCOMES: 1. Primary outcome The primary outcome is Time To Clinical Improvement (TTCI). By definition, TTCI is the time (days) it takes to downgrade two levels from the following six ordered grades [(grade 1) discharge to (grade 6) death] in the clinical state of admission to the start of study treatments (hDPSCs or placebo). Six grades of ordered variables: 2. Secondary outcomes 2.1 vital signs: heart rate, blood pressure (systolic blood pressure, diastolic blood pressure). During the screening period, hospitalization every day (additional time points of D1, D4, D7 30min before injection, 2h ± 30min, 24h ± 30min after the injection) and follow-up period D90 ± 3 days. 2.2 Laboratory examinations: during the screening period, 30 minutes before D1, D4, D7 infusion, 2h ± 30min, 24h ± 30min after the end of infusion, D10, D14, D28 during hospitalization or discharge day and follow-up period D90 ± 3 days. 2.3 Blood routine: white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, basophils, neutrophils, lymphocytes, monocytes, eosinophils Acidic granulocyte count, basophil count, red blood cell, hemoglobin, hematocrit, average volume of red blood cells, average red blood cell Hb content, average red blood cell Hb concentration, RDW standard deviation, RDW coefficient of variation, platelet count, platelet specific platelet average Volume, platelet distribution width,% of large platelets; 2.4 Liver and kidney function tests: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyl transferase, prealbumin, total protein, albumin, globulin, white / globule ratio , Total bilirubin, direct bilirubin, cholinesterase, urea, creatinine, total carbon dioxide, uric acid glucose, potassium, sodium, chlorine, calcium, corrected calcium, magnesium, phosphorus, calcium and phosphorus product, anion gap, penetration Pressure, total cholesterol, triacylglycerol, high density lipoprotein cholesterol, Low density lipoprotein cholesterol, lipoprotein a, creatine kinase, lactate dehydrogenase, estimated glomerular filtration rate. 2.5 Inflammation indicators: hypersensitive C-reactive protein, serum amyloid (SAA); 2.6 Infectious disease testing: Hepatitis B (HBsAg, HBsAb, HBeAg, HBeAb, HBcAb), Hepatitis C (Anti-HCV), AIDS (HIVcombin), syphilis (Anti-TP), cytomegalovirus CMV-IgM, cytomegalovirus CMV-IgG; only during the screening period and follow-up period D90 ± 3. 2.7 Immunological testing: Collect peripheral blood to detect the phenotype of T lymphocyte, B lymphocyte, natural killer cell, Macrophage and neutrophil by using flow cytometry. Collect peripheral blood to detect the gene profile of mononuclear cells by using single-cell analyses. Collect peripheral blood serum to detect various immunoglobulin changes: IgA, IgG, IgM, total IgE; Collect peripheral blood serum to explore the changes of cytokines, Th1 cytokines (IL-1 β, IL-2, TNF-a, ITN-γ), Th2 cytokines (IL-4, IL-6, IL -10). 2.8 Pregnancy test: blood β-HCG, female subjects before menopause are examined during the screening period and follow-up period D90 ± 3. 2.9 Urine routine: color, clarity, urine sugar, bilirubin, ketone bodies, specific gravity, pH, urobilinogen, nitrite, protein, occult blood, leukocyte enzymes, red blood cells, white blood cells, epithelial cells, non-squamous epithelial cells , Transparent cast, pathological cast, crystal, fungus; 2.10 Stool Routine: color, traits, white blood cells, red blood cells, fat globules, eggs of parasites, fungi, occult blood (chemical method), occult blood (immune method), transferrin (2h ± 30min after the injection and not detected after discharge). RANDOMIZATION: Block randomization method will be applied by computer to allocate the participants into experimental and control groups. The random ratio is 1:1. BLINDING (MASKING): Participants, outcomes assessors and investigators (including personnel in laboratory and imaging department who issue the sample report or image observations) will be blinded. Injections of cell suspension and saline will be coded in accordance with the patient’s randomisation group. The blind strategy is kept by an investigator who does not deliver the medical care or assess primary outcome results. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): Twenty participants will be randomized to the experimental and control groups (10 per group). TRIAL STATUS: Protocol version number, hDPSC-CoVID-2019-02-2020 Version 2.0, March 13, 2020. Patients screening commenced on 16(th) April and an estimated date of the recruitment of the final participants will be around end of July. . TRIAL REGISTRATION: Registration: World Health Organization Trial Registry: ChiCTR2000031319; March 27,2020. ClinicalTrials.gov Identifier: NCT04336254; April 7, 2020 Other Study ID Numbers: hDPSC-CoVID-2019-02-2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Mayo Clinic Strategies for COVID-19 Avoiding a Medical Education Quarantine During the Pandemic


Adverse drug reactions and interactions: first reports and special situations


title: Chapter 34 Mannose–fucose recognition by DC-SIGN

text: Publisher Summary Dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN). DC-SIGN is a C-type lectin receptor that recognizes N-linked high-mannose oligosaccharides and branched fucosylated structures. It is now clear that the biological role of DC-SIGN is two-fold. It is primarily expressed by dendritic cells and mediates important functions necessary for the induction of successful immune responses that are essential for the clearance of microbial infections, such as the capture, destruction, and presentation of microbial pathogens to induce successful immune responses. Yet, on the other hand, pathogens may also exploit DC-SIGN to modulate DC functioning thereby skewing the immune response and promoting their own survival. This chapter presents an overview of the structure of DC-SIGN and its expression pattern among immune cells. The current state of knowledge of DC-SIGN-carbohydrate interactions is discussed and how these interactions influence dendritic cell functioning is examined. The molecular aspects that underlie the selectivity of DC-SIGN for mannose-and fucose-containing carbohydrates are detailed. Furthermore, the chapter discusses the role of DC-SIGN in dendritic cell biology and how certain bacterial pathogens exploit DC-SIGN to escape immune surveillance.


title: Coronavirus (COVID‐19): Patient experience—Administrative services on the frontline during crisis

text: The COVID‐19 pandemic has had a dramatic impact on care delivery among health care institutions and providers in the United States. As a categorical cancer center, MD Anderson has prioritized care for our patients based on acuity of their disease. We continue to implement measures to protect patients and employees from acquiring the infection within our facilities, and to provide acute management of cancer patients with concomitant COVID‐19 infections who are considered at high risk of death. The Division of Patient Experience, formerly established in October 2016, has played an integral role in the institution's pandemic response from its inception. The team actively supported programs and processes in anticipation of the pandemic's effect on our patients and employees. We will describe how the team continues to serve in the ever‐dynamic environment as we approach the expected surge in COVID‐19 cases among our patient population, our employees, and in our community.


title: Correction: Middle East Respiratory Syndrome Coronavirus Intra-Host Populations Are Characterized by Numerous High Frequency Variants

text: [This corrects the article DOI: 10.1371/journal.pone.0146251.].


title: Unveiling cultures in emergency response communication networks on social media: following the 2016 Louisiana floods

text: While culture in emergency management has gained attention from the field of risk communication, few have systemically dealt with the nuances of general culture involved in the formation and differentiation of risk communication. To fill this gap, this research aims to first examine cultural nuances from the 2016 Louisiana flood response by primarily focusing on communications embedded in social media. The results from social network analysis and content analysis highlight that the flood response communication had strong cultural characteristics, highlighting the notion that of the cultures in Louisiana—faith-based, local authority, and nonprofits—were the prominent cultural responders in the flood response communication. In particular, cultural similarity in both intra/inter group response communication was observed, with each communication group comprising actors who shared a common cultural background and spoke similar keywords.


title: Clinical Characteristics and Results of Semen Tests Among Men With Coronavirus Disease 2019

text: This cohort study examines the clinical characteristics of men with coronavirus disease 2019 whose semen tested positive for severe acute respiratory syndrome coronavirus 2.


title: Estimation of the number of blood donors during the COVID‐19 incubation period across China and analysis of prevention and control measures for blood transfusion transmission

text: BACKGROUND: The aim of this study was to estimate the number of blood donors during the COVID‐19 incubation period across China. STUDY DESIGN AND METHODS: In this study, we developed a predictive model to estimate the number of blood donors during the COVID‐19 incubation period among 34 provincial regions in China. Our main assumption was that blood donors of all ages in different regions have a stable blood donation intention and the same infection risk. RESULTS: First, we estimated the number of blood donors during the COVID‐19 incubation period in Wuhan city, Hubei Province, and China, from December 31, 2019 to March 17, 2020. Second, we compared the number of blood donors during the COVID‐19 incubation period in all provinces across China. In addition, we found that if all RBCs, plasma, and cryoprecipitation were stored in isolation until the 14th day, the potential risk of SARS‐CoV‐2 transmission through blood transfusion was reduced by at least 65.77% after the blood donor safely passed the COVID‐19 incubation period. Moreover, if the detection of SARS‐CoV‐2 RNA was carried out on all platelets, the potential risk would be reduced by 77.48%. CONCLUSIONS: Although the risk is low, with the rapid spread of the COVID‐19 and the appearance of alarmingly high infectivity and a high fatality rate, appropriate measures should be taken by health departments to ensure the safety of clinical blood.


title: Similarities between the Yin/Yang Doctrine and Hormesis in Toxicology and Pharmacology

text: Hormesis is a generalizable dose–response relationship characterized by low-dose stimulation and high-dose inhibition. Despite debate over this biphasic dose–response curve, hormesis is challenging central beliefs in the evaluation of chemicals or drugs and has influenced biological model selection, concentration range, study design, and hypothesis testing. We integrate the traditional Chinese philosophy – Yin/Yang doctrine – into the representation of the Western hormetic dose–response relationship and review the Yin/Yang historical philosophy contained in the hormesis concept, aiming to promote general acceptance and wider applications of hormesis. We suggest that the Yin/Yang doctrine embodies the hormetic dose–response, including the relationship between the opposing components, curve shape, and time-dependence, and may afford insights that clarify the hormetic dose–response relationship in toxicology and pharmacology.


title: International surgical guidance for COVID-19: Validation using an international Delphi process - Cross-sectional study

text: BACKGROUND: International professional bodies have been quick to disseminate initial guidance documents during the COVID-19 pandemic. In the absence of firm evidence, these have been developed by expert committees, limited in participant number. This study aimed to validate international COVID-19 surgical guidance using a rapid Delphi consensus exercise. METHODS: Delphi statements were directly mapped to guidance from surgical professional bodies in the US and Europe (SAGES/EAES), the UK (Joint RCS), and Australasia (RACS), to validate content against international consensus. Agreement from ≥70% participants was determined as consensus agreement. RESULTS: The Delphi exercise was completed by 339 individuals from 41 countries and 52 statements were mapped to the guidance, 47 (90.4%) reaching consensus agreement. Of these, 27 statements were mapped to SAGES/EAES guidance, 21 to the Joint RCS document, and 33 to the RACS document. Within the SAGES/EAES document, 92.9% of items reached consensus agreement (median 89.0%, range 60.5–99.2%), 90.4% within the Joint RCS document (87.6%, 63.4–97.9%), and 90.9% within the RACS document (85.5%, 18.7–98.8%). Statements lacking consensus related to the surgical approach (open vs. laparoscopic), dual consultant operating, separate instrument decontamination, and stoma formation rather than anastomosis. CONCLUSION: Initial surgical COVID-19 guidance from the US, Europe and Australasia was widely supported by an international expert community, although a small number of contentious areas emerged. These findings should be addressed in future guidance iterations, and should stimulate urgent investigation of non-consensus areas.


title: Health Communication during SARS

text: During the severe acute respiratory syndrome (SARS) outbreak, electronic media made it possible to disseminate prevention messages rapidly. The Centers for Disease Control and Prevention’s Travelers’ Health Web site was frequently visited in the first half of 2003; more than 2.6 million visits were made to travel alerts, advisories, and other SARS-related documents.


title: Rapid quantitative detection of Yersinia pestis by lateral-flow immunoassay and up-converting phosphor technology-based biosensor

text: Abstract Up-converting phosphor technology (UPT)-based lateral-flow immunoassay has been developed for quantitative detection of Yersinia pestis rapidly and specifically. In this assay, 400nm up-converting phosphor particles were used as the reporter. A sandwich immumoassay was employed by using a polyclonal antibody against F1 antigen of Y. pestis immobilized on the nitrocellulose membrane and the same antibody conjugated to the UPT particles. The signal detection of the strips was performed by the UPT-based biosensor that could provide a 980nm IR laser to excite the phosphor particles, then collect the visible luminescence emitted by the UPT particles and finally convert it to the voltage as a signal. V T and V C stand for the multiplied voltage units for the test and the control line, respectively, and the ratio V T/V C is directly proportional to the number of Y. pestis in a sample. We observed a good linearity between the ratio and logCFU/ml of Y. pestis above the detection limit, which was approximately 104 CFU/ml. The precision of the intra- and inter-assay was below 15% (coefficient of variation, CV). Cross-reactivity with related Gram-negative enteric bacteria was not found. The UPT-LF immunoassay system presented here takes less than 30min to perform from the sample treatment to the data analysis. The current paper includes only preliminary data concerning the biomedical aspects of the assay, but is more concentrated on the technical details of establishing a rapid manual assay using a state-of-the-art label chemistry.


title: 10.17 Metabolism of Glutathione S-Conjugates: Multiple Pathways

text: This is an update of Cooper, A.J.L., Hanigan, M.H., Enzymes Involved in Processing Glutathione Conjugates, Comprehensive Toxicology, Second Edition, edited by Charlene A. McQueen, Elsevier, Oxford, 2010, Volume 4, Pages 323–366.


title: Contribution of Host Intracellular Transport Machineries to Intercellular Movement of Turnip Mosaic Virus

text: The contribution of different host cell transport systems in the intercellular movement of turnip mosaic virus (TuMV) was investigated. To discriminate between primary infections and secondary infections associated with the virus intercellular movement, a gene cassette expressing GFP-HDEL was inserted adjacent to a TuMV infectious cassette expressing 6K(2):mCherry, both within the T-DNA borders of the binary vector pCambia. In this system, both gene cassettes were delivered to the same cell by a single binary vector and primary infection foci emitted green and red fluorescence while secondarily infected cells emitted only red fluorescence. Intercellular movement was measured at 72 hours post infiltration and was estimated to proceed at an average rate of one cell being infected every three hours over an observation period of 17 hours. To determine if the secretory pathway were important for TuMV intercellular movement, chemical and protein inhibitors that blocked both early and late secretory pathways were used. Treatment with Brefeldin A or Concanamycin A or expression of ARF1 or RAB-E1d dominant negative mutants, all of which inhibit pre- or post-Golgi transport, reduced intercellular movement by the virus. These treatments, however, did not inhibit virus replication in primary infected cells. Pharmacological interference assays using Tyrphostin A23 or Wortmannin showed that endocytosis was not important for TuMV intercellular movement. Lack of co-localization by endocytosed FM4-64 and Ara7 (AtRabF2b) with TuMV-induced 6K(2)-tagged vesicles further supported this conclusion. Microfilament depolymerizing drugs and silencing expression of myosin XI-2 gene, but not myosin VIII genes, also inhibited TuMV intercellular movement. Expression of dominant negative myosin mutants confirmed the role played by myosin XI-2 as well as by myosin XI-K in TuMV intercellular movement. Using this dual gene cassette expression system and transport inhibitors, components of the secretory and actomyosin machinery were shown to be important for TuMV intercellular spread.


title: Viral Loads in Clinical Specimens and SARS Manifestations

text: A retrospective viral load study was performed on clinical specimens from 154 patients with laboratory-confirmed severe acute respiratory syndrome (SARS); the specimens were prospectively collected during patients' illness. Viral load in nasopharyngeal aspirates (n = 142) from day 10 to day 15 after onset of symptoms was associated with oxygen desaturation, mechanical ventilation, diarrhea, hepatic dysfunction, and death. Serum viral load (n = 53) was associated with oxygen desaturation, mechanical ventilation, and death. Stool viral load (n = 94) was associated with diarrhea, and urine viral load (n = 111) was associated with abnormal urinalysis results. Viral replications at different sites are important in the pathogenesis of clinical and laboratory abnormalities of SARS.


title: Prisons confinées: quelles conséquences pour les soins psychiatriques et la santé mentale des personnes détenues en France?

text: Résumé Objectif. En France, les mesures de confinement ont été accompagnées de dispositions spécifiques pour les prisons: suspension des activités, parloirs et interventions extérieures. Plus de dix mille personnes détenues ont en outre été libérées pour diminuer le taux d’occupation des établissements et limiter la propagation du virus. L’objectif de cet article est de décrire la réorganisation des soins psychiatriques en milieu pénitentiaire en contexte de pandémie de Covid-19 et d’interroger les conséquences du confinement et des libérations anticipées sur la santé mentale des personnes détenues. Méthode. Ce travail s’appuie sur une enquête menée en avril 2020 auprès des soignants de 42 unités sanitaires en milieu pénitentiaire et des 9 unités hospitalières spécialement aménagées en France. Une synthèse de la littérature internationale sur la question des soins psychiatriques en milieu pénitentiaire durant l’épidémie de Covid-19 a également été réalisée. Résultats. L’épidémie de Covid-19 semble avoir été plutôt contenue dans les prisons françaises au cours de la période de confinement mais le poids des mesures mises en place sur la population carcérale est important. Les 3 niveaux de soins psychiatriques en milieu pénitentiaire ont instauré des mesures spécifiques pour assurer la continuité des soins, accompagner les personnes incarcérées et contenir l’épidémie. Parmi les plus importantes, on note la restriction des consultations, la création de « secteurs Covid », la déprogrammation des hospitalisations non urgentes, le renforcement des mesures d’hygiène et le remaniement des effectifs. Actuellement, les soignants sont principalement confrontés à des sevrages forcés, des symptomatologies anxieuses et des décompensations de troubles psychiatriques chroniques. Certaines libérations anticipées sont aussi très préoccupantes, pouvant entraîner des ruptures de soins, par manque de préparation des relais de prise en charge. Discussion. Les remaniements en lien avec le confinement donnent une visibilité accrue au fossé qui sépare la psychiatrie en milieu libre de la psychiatrie en milieu pénitentiaire. Il nous apparaît important de rappeler la vulnérabilité des personnes incarcérées qui doivent impérativement être considérées dans les politiques de santé publique. Abstract Objective. The impact of the Covid-19 pandemic on the 11 million people currently incarcerated worldwide is the subject of many concerns. Prisons and jails are filled with people suffering from many preexisting medical conditions increasing the risk of complications. Detainees’ access to medical services is already limited and overcrowding poses a threat of massive contagion. Beyond the health impact of the crisis, the tightening of prison conditions worries. On March 16, 2020, in France, the lockdown measures have been accompanied by specific provisions for prisons: all facilities have suspended visitations, group activities and external interventions. Over 10 000 prisoners have been released to reduce the prison population and the risk of virus propagation. These adjustments had major consequences on the healthcare system in French prisons. The objectives of this article are to describe the reorganization of the three levels of psychiatric care for inmates in France in the context of Covid-19 pandemic and to have a look at the impact of lockdown measures and early releases on mental health of prisoners. Methods. This work is based on a survey conducted in April 2020 in France among psychiatric healthcare providers working in 42 ambulatory units for inmates and in the 9 full-time inpatient psychiatric wards exclusively for inmates called “UHSAs” (which stands for “unités hospitalières spécialement aménagées”, and can be translated as “specially equipped hospital units”). A review of the international literature on mental healthcare system for inmates during the Covid-19 epidemic has also been performed. Results. The Covid-19 epidemic has been rather contained during the period of confinement in French prisons but the impact of confinement measures on the prison population is significant. The three levels of psychiatric care for inmates have implemented specific measures to ensure continuity of care, to support detainees during Coronavirus lockdown and to prevent an infection’s spread. Among the most important are: limitation of medical consultations to serious and urgent cases, creation of “Covid units”, cancellation of voluntary psychiatric hospitalizations, reinforcement of preventive hygiene measures and reshuffling of medical staff. Prolonged confinement has consequences on mental health of detainees. Currently, mental health workers are facing multiple clinical situations such as forced drug and substance withdrawal (linked to difficulties in supplying psychoactive substances), symptoms of anxiety (due to concerns for their own and their relatives’ wellbeing) and decompensation among patients with severe psychiatric conditions. Early releases from prison may also raise some issues. People recently released from prison are identified as at high risk of death by suicide and drug overdose. The lack of time to provide the necessary link between health services within prisons and health structures outside, could have serious consequences, emphasizing the well-known “revolving prison doors” effect. Discussion. The current lockdown measures applied in French jails and prisons point out the disparities between psychiatric care for inmates and psychiatric care for general population. Giving the high vulnerability of prison population, public health authorities should pay more attention to health care in prisons.


title: Dietary Probiotic Compound Improves Reproductive Performance of Porcine Epidemic Diarrhea Virus-Infected Sows Reared in a Japanese Commercial Swine Farm under Vaccine Control Condition

text: Lactogenic immunity transferred to piglets after inoculation of a live vaccine to pregnant sows was proved limited to control porcine epidemic diarrhea (PED). Hence, here we evaluated the efficacy of administration of a probiotic compound containing Bacillus mesentericus, Clostridium butyricum, and Enterococcus faecalis together with a commercial live-attenuated PED vaccine (Nisseiken PED Live Vaccine, Nisseiken, Tokyo, Japan) to improve the health and reproductive performance of PED-infected sows. Twenty pregnant sows in a PED-positive farm were equally divided into probiotics-administered (VP) and control (VC) sow groups. A commercial live-attenuated vaccine was injected as per the manufacturer’s instruction. The probiotic compound (15 g/day) was orally administered to VP from 6 weeks pre-parturition to 7 days post-parturition (ppd7). VP had a significantly higher body weight at ppd7 than VC (191 vs 186 kg; P < 0.05). At day 3 post-parturition (ppd3) (4.18 vs 3.63 kg/day) and ppd7 (5.14 vs 4.34 kg/day), milk produced by VP was significantly (P < 0.05) greater than that by VC. Total immunoglobulin (Ig)A and IgG concentrations at day 0 were significantly (P < 0.05) higher in whey of VP (1.9 and 6.6 g/dL, respectively) than in that of VC (1.7 and 6.1 g/dL, respectively). However, total IgG concentration in whey of VP and VC at ppd3 and ppd7 did not differ. Antibody titer was significantly higher at day 0 in serum of VP than it was that of VC (60 vs 37 in geometric mean; P < 0.05). Likewise, the antibody titer in whey of VP and VC was found to be similar at day 0 (416 vs 208 in geometric mean; P = 0.13). Consequently, VP had fewer days between weaning and return to estrus than did VC (7 vs 10 days; P < 0.05). Moreover, piglets of VP had a significantly (P < 0.05) higher litter weight at birth (9,252 g/litter) and a lower mortality (12%) during suckling than those of VC (8,686 g/litter and 28%, respectively). In summary, probiotic-supplemented, PED-vaccinated sows were healthier, transferred PED-specific antibodies via colostrum to piglets, had greater litter weight at birth, and reduced mortality during suckling.


COVID‐19 convalescent plasma: phase 2


title: SINS model in the management of biosafety level 2 laboratories: exploration and practice

text: Abstract A significant number of biosafety level 2 (BSL-2) laboratories have been established in many countries for studies of various types of pathogenic agents and other infectious biological materials. The harmonized management of biological risks in such diverse laboratories thus appears as a real challenge. Zhejiang Province in China has taken the initiative to establish a comprehensively integrated laboratory biosafety management system called SINS (Standardization, Informatization, Normalization and Systematization). The SINS model system has been introduced and adopted in 1,721 BSL-2 laboratories in Zhejiang Province, and thus lead to an increase in the number of biosafety committees from 20% to more than 95% from 2007 to 2018, and the number of biosafety laboratory managers who knows biosafety-related laws and regulations increase from 52.7% to 83.7% from 2009 to 2017. Such achievements indicate that the successful implementation of SINS model has increased the effective control of biological risks in BSL-2 laboratories of the Zhejiang Province. SINS model and its main effects on leading the improvement of laboratory biosafety management was presented in this review. The SINS model helps to strengthen laboratory biosafety and thus effectively reduces occurrence of biosafety-related incidences. This model can potentially be used by other regions or countries where harmonized biosafety management system is still under-developing.


title: Learning from the Past: Possible Urgent Prevention and Treatment Options for Severe Acute Respiratory Infections Caused by 2019‐nCoV

text: With the current trajectory of the 2019‐nCoV outbreak unknown, public health and medicinal measures will both be needed to contain spreading of the virus and to optimize patient outcomes. Although little is known about the virus, an examination of the genome sequence shows strong homology with its better‐studied cousin, SARS‐CoV. The spike protein used for host cell infection shows key nonsynonymous mutations that might hamper the efficacy of previously developed therapeutics but remains a viable target for the development of biologics and macrocyclic peptides. Other key drug targets, including RNA‐dependent RNA polymerase and coronavirus main proteinase (3CLpro), share a strikingly high (>95 %) homology to SARS‐CoV. Herein, we suggest four potential drug candidates (an ACE2‐based peptide, remdesivir, 3CLpro‐1 and a novel vinylsulfone protease inhibitor) that could be used to treat patients suffering with the 2019‐nCoV. We also summarize previous efforts into drugging these targets and hope to help in the development of broad‐spectrum anti‐coronaviral agents for future epidemics.


title: Genomic Sequencing of the Severe Acute Respiratory Syndrome-Coronavirus

text: The polymerase chain reaction (PCR), which can exponentially replicate a target DNA sequence, has formed the basis for the sensitive and direct examination of clinical samples for evidence of infection. During the epidemic of severe acute respiratory syndrome (SARS) in 2003, PCR not only offered a rapid way to diagnose SARS-coronavirus (SARS-CoV) infection, but also made the molecular analysis of its genomic sequence possible. Sequence variations were observed in the SAR-CoV obtained from different patients in this epidemic. These unique viral genetic signatures can be applied as a powerful molecular tool in tracing the route of transmission and in studying the genome evolution of SARS-CoV. To extract this wealth of information from the limited primary clinical specimens of SARS patients, we were presented with the challenge of efficiently amplifying fragments of the SARS-CoV genome for analysis. In this chapter, we will discuss how we managed to accomplish this task with our optimized protocols on reversetranscription, nested PCR amplification, and DNA cycle sequencing. We will also discuss the sequence variations that typified some strains of SARS-CoV in the different phases during this epidemic. PCR amplification of the viral sequence and genomic sequencing of these critical sequence variations of re-emerging SARS-CoV strains would give us quick insights into the virus.


COVID-19 and opportunities for international cooperation in health.


title: A long-term animal experiment indicating persistent infection of bovine coronavirus in cattle

text: A long-term animal experiment involving inoculation with bovine coronavirus (BCoV) was conducted to verify its persistent infection in cattle. Three colostrum-deprived Holstein calves were housed separately in individual rooms of a high-containment facility and inoculated with the BCoV strain Kumamoto/1/07. Until the end of the experiment (1,085, 700 and 280 days, respectively), viral RNAs were detected sporadically by RT-PCR and nested PCR from plasma, nasal discharge, and feces. Seroconversion and titer changes were validated by hemagglutination inhibition tests and neutralization tests. Among the samples, nasal discharge showed a higher viral positivity than feces, which seemed to be associated with positive detection in the plasma. These data demonstrate the existence of persistent infection of BCoV in the respiratory tissues of cattle.


title: Update in the treatment of non-influenza respiratory virus infection in solid organ transplant recipients

text: Introduction: Despite the improved outcomes in solid organ transplantation with regard to prevention of rejection and increased patient and graft survival, infection remains a common cause of morbidity and mortality. Respiratory viruses are a frequent and potentially serious cause of infection after solid organ transplantation. Furthermore, clinical manifestations of respiratory virus infection (RVI) may be more severe and unusual in solid organ transplant recipients (SOTRs) compared with the non-immunocompromised population. Areas covered: This article reviews the non-influenza RVIs that are commonly encountered in SOTRs. Epidemiologic and clinical characteristics are highlighted and available treatment options are discussed. Expert opinion: New diagnostic tools, particularly rapid molecular assays, have expanded the ability to identify specific RVI pathogens in SOTRs. This is not only useful from a treatment standpoint but also to guide infection control practices. More data are needed on RVIs in the solid organ transplant population, particularly regarding their effect on rejection and graft dysfunction. There is also a need for new antiviral agents active against these infections as well as markers that can identify which patients would most benefit from treatment.


title: An In-Silico Investigation of Phytochemicals as Antiviral Agents Against Dengue Fever

text: Abstract: A virtual screening analysis of our library of phytochemical structures with dengue virus protein targets has been carried out using a molecular docking approach. A total of 2194 plant-derived secondary metabolites have been docked. This molecule set comprised of 290 alkaloids (68 indole alkaloids, 153 isoquinoline alkaloids, 5 quinoline alkaloids, 13 piperidine alkaloids, 14 steroidal alkaloids, and 37 miscellaneous alkaloids), 678 terpenoids (47 monoterpenoids, 169 sesquiterpenoids, 265 diterpenoids, 81 steroids, and 96 triterpenoids), 20 aurones, 81 chalcones, 349 flavonoids, 120 isoflavonoids, 74 lignans, 58 stilbenoids, 169 miscellaneous polyphenolic compounds, 100 coumarins, 28 xanthones, 67 quinones, and 160 miscellaneous phytochemicals. Dengue virus protein targets examined included dengue virus protease (NS2B-NS3pro), helicase (NS3 helicase), methyltransferase (MTase), RNA-dependent RNA polymerase (RdRp), and the dengue virus envelope protein. Polyphenolic compounds, flavonoids, chalcones, and other phenolics were the most numerous of the strongly docking ligands for dengue virus protein targets.


title: COVID-19 Pandemic: Knowledge and Perceptions of the Public and Healthcare Professionals

text: Background and objective The recent pandemic due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a major concern for the people and governments across the world due to its impact on individuals as well as on public health. The infectiousness and the quick spread across the world make it an important event in everyone’s life, often evoking fear. Our study aims at assessing the overall knowledge and perceptions, and identifying the trusted sources of information for both the general public and healthcare personnel. Materials and methods This is a questionnaire-based survey taken by a total of 1,246 respondents, out of which 744 belonged to the healthcare personnel and 502 were laypersons/general public. There were two different questionnaires for both groups. The questions were framed using information from the World Health Organization (WHO), UpToDate, Indian Council of Medical Research (ICMR), Center for Disease Control (CDC), National Institute of Health (NIH), and New England Journal of Medicine (NEJM) website resources. The questions assessed awareness, attitude, and possible practices towards ensuring safety for themselves as well as breaking the chain of transmission. A convenient sampling method was used for data collection. Descriptive statistics [mean(SD), frequency(%)] were used to portray the characteristics of the participants as well as their awareness, sources of information, attitudes, and practices related to SARS-CoV-2. Results The majority (94.3%) of the respondents were Indians. About 80% of the healthcare professionals and 82% of the general public were worried about being infected. Various websites such as ICMR, WHO, CDC, etc., were a major source of information for the healthcare professional while the general public relied on television. Almost 98% of healthcare professionals and 97% of the general public, respectively, identified ‘Difficulty in breathing” as the main symptom. More than 90% of the respondents in both groups knew and practiced different precautionary measures. A minority of the respondents (28.9% of healthcare professionals and 26.5% of the general public) knew that there was no known cure yet. Almost all respondents from both the groups agreed on seeking medical help if breathing difficulty is involved and self-quarantine if required. Conclusion Most healthcare professionals and the general public that we surveyed were well informed about SARS-CoV-2 and have been taking adequate measures in preventing the spread of the same. There is a high trust of the public in the government. There are common trusted sources of information and these need to be optimally utilized to spread accurate information.


title: Severe Acute Respiratory Illness Deaths in Sub-Saharan Africa and the Role of Influenza: A Case Series From 8 Countries

text: Background. Data on causes of death due to respiratory illness in Africa are limited. Methods. From January to April 2013, 28 African countries were invited to participate in a review of severe acute respiratory illness (SARI)–associated deaths identified from influenza surveillance during 2009–2012. Results. Twenty-three countries (82%) responded, 11 (48%) collect mortality data, and 8 provided data. Data were collected from 37 714 SARI cases, and 3091 (8.2%; range by country, 5.1%–25.9%) tested positive for influenza virus. There were 1073 deaths (2.8%; range by country, 0.1%–5.3%) reported, among which influenza virus was detected in 57 (5.3%). Case-fatality proportion (CFP) was higher among countries with systematic death reporting than among those with sporadic reporting. The influenza-associated CFP was 1.8% (57 of 3091), compared with 2.9% (1016 of 34 623) for influenza virus–negative cases (P < .001). Among 834 deaths (77.7%) tested for other respiratory pathogens, rhinovirus (107 [12.8%]), adenovirus (64 [6.0%]), respiratory syncytial virus (60 [5.6%]), and Streptococcus pneumoniae (57 [5.3%]) were most commonly identified. Among 1073 deaths, 402 (37.5%) involved people aged 0–4 years, 462 (43.1%) involved people aged 5–49 years, and 209 (19.5%) involved people aged ≥50 years. Conclusions. Few African countries systematically collect data on outcomes of people hospitalized with respiratory illness. Stronger surveillance for deaths due to respiratory illness may identify risk groups for targeted vaccine use and other prevention strategies.


title: Policy and Pandemic: The Changing Practice of Nephrology During the COVID-19 Outbreak

text: ABSTRACT The coronavirus (COVID-19) pandemic has changed care delivery for patients with end-stage kidney disease (ESKD). We explore the United States healthcare system as it pertains to dialysis care, including existing policies, modifications implemented in response to the COVID-19 crisis, and possible next steps for policy makers and nephrologists. This includes policies related to resource management, use of telemedicine, prioritization of dialysis access procedures, expansion of home dialysis modalities, administrative duties, and quality assessment. The government has already established policies that have instated some flexibilities to help providers focus their response to the crisis. However, future policy during and following the COVID-19 pandemic can bolster our ability to optimize care for patients with ESKD. Key themes in this perspective are the importance of policy flexibility, clear strategies for emergency preparedness, and robust health systems that maximize accessibility and patient autonomy.


title: Rotavirus prevalence and relationships with climatological factors in gabon, africa

text: A one‐year study of rotavirus prevalence was carried out using electron microscopy in Gabon, equatorial Africa. One hundred fifty‐six nonhospitalized diarrheic children up to 10 years of age and 115 age‐matched controls were investigated together with diarrheic adults and children over 10 years of age. Rotaviruses were observed only in diarrheic children under 10 years of age (10.2%). Rotaviruses were more prevalent in the dry‐season months (19.2% versus 1.3%, P < .001). Rotaviruses were the most commonly found among all the viral, bacterial, and parasitic agents we detected, with the exception of the coronaviruslike particles, which are the subject of another paper [Sitbon, 1985].


Non Structural Proteins 8 and 9 of Human Coronavirus 229E


Will the COVID-19 pandemic accelerate the implementation of single-day coronary angioplasty in Poland?


title: Offering patients more: how the West Africa Ebola outbreak can shape innovation in therapeutic research for emerging and epidemic infections

text: Although, after an epidemic of over 28 000 cases, there are still no licensed treatments for Ebola virus disease (EVD), significant progress was made during the West Africa outbreak. The pace of pre-clinical development was exceptional and a number of therapeutic clinical trials were conducted in the face of considerable challenges. Given the on-going risk of emerging infectious disease outbreaks in an era of unprecedented population density, international travel and human impact on the environment it is pertinent to focus on improving the research and development landscape for treatments of emerging and epidemic-prone infections. This is especially the case since there are no licensed therapeutics for some of the diseases considered by the World Health Organization as most likely to cause severe outbreaks—including Middle East respiratory syndrome coronavirus, Marburg virus, Crimean Congo haemorrhagic fever and Nipah virus. EVD, therefore, provides a timely exemplar to discuss the barriers, enablers and incentives needed to find effective treatments in advance of health emergencies caused by emerging infectious diseases. This article is part of the themed issue ‘The 2013–2016 West African Ebola epidemic: data, decision-making and disease control’.


title: Improving immunological insights into the ferret model of human viral infectious disease

text: Ferrets are a well‐established model for studying both the pathogenesis and transmission of human respiratory viruses and evaluation of antiviral vaccines. Advanced immunological studies would add substantial value to the ferret models of disease but are hindered by the low number of ferret‐reactive reagents available for flow cytometry and immunohistochemistry. Nevertheless, progress has been made to understand immune responses in the ferret model with a limited set of ferret‐specific reagents and assays. This review examines current immunological insights gained from the ferret model across relevant human respiratory diseases, with a focus on influenza viruses. We highlight key knowledge gaps that need to be bridged to advance the utility of ferrets for immunological studies.


title: Landscape of emerging and re-emerging infectious diseases in China: impact of ecology, climate, and behavior

text: For the past several decades, the infectious disease profile in China has been shifting with rapid developments in social and economic aspects, environment, quality of food, water, housing, and public health infrastructure. Notably, 5 notifiable infectious diseases have been almost eradicated, and the incidence of 18 additional notifiable infectious diseases has been significantly reduced. Unexpectedly, the incidence of over 10 notifiable infectious diseases, including HIV, brucellosis, syphilis, and dengue fever, has been increasing. Nevertheless, frequent infectious disease outbreaks/events have been reported almost every year, and imported infectious diseases have increased since 2015. New pathogens and over 100 new genotypes or serotypes of known pathogens have been identified. Some infectious diseases seem to be exacerbated by various factors, including rapid urbanization, large numbers of migrant workers, changes in climate, ecology, and policies, such as returning farmland to forests. This review summarizes the current experiences and lessons from China in managing emerging and re-emerging infectious diseases, especially the effects of ecology, climate, and behavior, which should have merits in helping other countries to control and prevent infectious diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available in the online version of this article at 10.1007/s11684-017-0605-9 and is accessible for authorized users.


title: The type I interferon response during viral infections: a “SWOT” analysis

text: The type I interferon (IFN) response is a strong and crucial moderator for the control of viral infections. The strength of this system is illustrated by the fact that, despite some temporary discomfort like a common cold or diarrhea, most viral infections will not cause major harm to the healthy immunocompetent host. To achieve this, the immune system is equipped with a wide array of pattern recognition receptors and the subsequent coordinated type I IFN response orchestrated by plasmacytoid dendritic cells (pDCs) and conventional dendritic cells (cDCs). The production of type I IFN subtypes by dendritic cells (DCs), but also other cells is crucial for the execution of many antiviral processes. Despite this coordinated response, morbidity and mortality are still common in viral disease due to the ability of viruses to exploit the weaknesses of the immune system. Viruses successfully evade immunity and infection can result in aberrant immune responses. However, these weaknesses also open opportunities for improvement via clinical interventions as can be seen in current vaccination and antiviral treatment programs. The application of IFNs, Toll‐like receptor ligands, DCs, and antiviral proteins is now being investigated to further limit viral infections. Unfortunately, a common threat during stimulation of immunity is the possible initiation or aggravation of autoimmunity. Also the translation from animal models to the human situation remains difficult. With a Strengths–Weaknesses–Opportunities–Threats (“SWOT”) analysis, we discuss the interaction between host and virus as well as (future) therapeutic options, related to the type I IFN system. Copyright © 2011 John Wiley & Sons, Ltd.


title: Chapter 10 Organization of Public Health Systems

text: Abstract Public health consists of a complex of activities of public and private organizations working to protect and promote the health of the population, within laws, regulations, legal precedents, and ethics to ensure individual rights as well as those of society. Elected governments in unitary or federal states have legislative, executive, and judicial functions with taxing and enforcement powers. Unitary countries have two levels of government: national and local; federal states have three: federal, state, and local. Each level has official public health responsibilities. Interaction with governmental, non-governmental, and professional organizations, and the public is vital to successful public health. Higher levels of government have greater tax resources, so cost sharing from state and national levels is essential. Low-income countries generally allocate low levels of funding to health and have weak public health infrastructures. Linkages among prevention, health promotion, and medical care are essential to meet population and individual health targets.