title: CORDITE: the curated CORona Drug InTERactions database for SARS-CoV-2

text: Summary Since the outbreak in 2019, researchers are trying to find effective drugs against the SARS-CoV-2 virus based on de novo drug design and drug repurposing. While the former approach is very time-consuming and needs extensive testing in humans, drug repurposing is more promising, as the drugs have already been tested for side-effects, etc. Currently, there is no treatment for COVID-19 that is clinically effective, but there is a huge amount of data from studies that analyze potential drugs. We developed CORDITE to efficiently combine state-of-the-art knowledge on potential drugs and make it accessible to scientists and clinicians. The web interface also provides access to an easy-to-use API that allows a wide use for other software and applications, e.g., for meta-analysis, design of new clinical studies, or simple literature search. CORDITE is currently empowering many scientists across all continents and accelerates research in the knowledge domains of virology and drug design. Availability: CORDITE is available athttps://cordite.mathematik.uni-marburg.de


title: Transmissible gastroenteritis virus N protein causes endoplasmic reticulum stress, up-regulates interleukin-8 expression and its subcellular localization in the porcine intestinal epithelial cell

text: Abstract This essay focuses on transmissible gastroenteritis virus (TGEV), which is an enteropathogenic virus related to contagious and acute diseases in suckling piglets. Previous literature suggests that the TGEV nucleocapsid protein (N) plays a significant role in viral transcriptional process, however, there is a need to examine other functions of TGEV N protein in the porcine intestinal epithelial cell (IEC) which is the target cell of TGEV. In the present study, we investigated the degradation, subcellular localisation, and function of TGEV N protein by examining its effects on cycle progression, endoplasmic reticulum (ER) stress, interleukin-8 (IL-8) expression, and cell survival. The results showed that TGEV N protein localised in the cytoplasm, inhibited IEC growth, prolonged the S-phase cell cycle by down-regulating cell cycle protein cyclin A, and was mainly degraded through the proteasome pathway. Moreover, TGEV N protein induced ER stress and activated NF-κB, which was responsible for the up-regulation of IL-8 and Bcl-2 expression. This report mainly considers the functions of TGEV N protein in IEC. To be specific, in IEC, TGEV N protein induces cell cycle prolongation at the S-phase, ER stress and up-regulates IL-8 expression. These results provide a better understanding of the functions and structural mechanisms of TGEV N protein.


title: Evaluating the consequences of health policy decisions

text: Uncertainty about intended and possible unintended side effects makes it important to evaluate changes following health policy decisions. A recent IJHPR article by Greenberg et al. evaluated changes in emergency department care following a directive of the Israeli Ministry of Health to limit occupancy in internal medicine wards. Over a six-year observation period, they found that one-month mortality and one-week readmissions after ED visits remained unchanged, while increases in average ED visit length, as well as increased delay time from ED admission to ward were observed. These findings help to assess the impact of the occupancy limit directive and may support future health policy decisions. However, the study by Greenberg et al. was limited by the unavailability of diagnostic data, and this illustrates a significant issue that transcends this particular study. In many countries, policy-relevant administrative data are not sufficiently available on a timely basis. Data availability is the prerequisite for monitoring developments in patterns of care following health policy changes. Besides conducting retrospective studies, timely availability of data makes it possible to establish monitoring systems which may help decision makers assess the impact of policy changes, identify undesired developments early, and recognize changes in need or demand of health services within the population.


title: A new look at brittle diabetes()

text: “Brittle diabetes” was first used to describe a life “disrupted by episodes of hypoglycemia or hyperglycemia.” Early descriptions focused on small case reports of mostly young women with psycho-social instability, recurrent diabetic ketoacidosis, poor patient compliance or maladaptation. We redefine “brittle diabetes” as occurring in four specific life stages each with distinct characteristics and associated conditions resulting in severely erratic glycemic control and poor outcomes. Once identified however these factors can often be reversed or significantly mitigated. The first group includes younger patients with associated psychiatric diseases such as bulimia and depression which require specific therapy and are treatable. A second group includes individuals who have another underlying medical condition resulting in disruption of insulin sensitivity or glucose utilization which must be sought. A third group, the largest we believe, has “geriatric type 1 diabetes” and develops severe glycemic instability due to frailty, chronic renal failure, dementia, vision loss, loss of counterregulation and other diseases of aging which lead to unintentional omission of insulin, insulin dosing errors and increasing insulin sensitivity. The fourth group, now seen around the world, suffers lack of insulin access and associated food insecurity. All four of these groups are described.


title: Coronavirus (COVID-19) Outbreak: What the Department of Radiology Should Know

text: Abstract In December 2019, a novel coronavirus (COVID-19) pneumonia emerged in Wuhan, China. Since then, this highly contagious COVID-19 has been spreading worldwide, with a rapid rise in the number of deaths. Novel COVID-19–infected pneumonia (NCIP) is characterized by fever, fatigue, dry cough, and dyspnea. A variety of chest imaging features have been reported, similar to those found in other types of coronavirus syndromes. The purpose of the present review is to briefly discuss the known epidemiology and the imaging findings of coronavirus syndromes, with a focus on the reported imaging findings of NCIP. Moreover, the authors review precautions and safety measures for radiology department personnel to manage patients with known or suspected NCIP. Implementation of a robust plan in the radiology department is required to prevent further transmission of the virus to patients and department staff members.


Risks of Hydroxychloroquine use for COVID-19 prophylaxis


title: The Impact of Ambient Environmental Exposures to Microbial Products on Asthma Outcomes from Birth to Childhood

text: PURPOSE OF REVIEW: Asthma is a chronic respiratory condition with increasing domestic and worldwide prevalence that burdens individuals and the healthcare system with high costs associated with long-term treatments and acute emergency room (ER) visits. It can be triggered by ambient microbes, including bacteria, viruses, and fungi. In this review, we examine the outcomes of asthma patients in relation to environmental exposures to ambient microbe products, focusing on whether exposure leads to asthma development from birth to childhood and if particular microbes are associated with worsened asthma exacerbations. RECENT FINDINGS: Bacterial endotoxin is more prominent in homes with pets and may cause cytokine cascades that lead to asthma exacerbation. However, some studies have demonstrated a protective effect with early exposure. Patients with positive Aspergillus skin testing are more prone to moderate-severe or severe-uncontrolled asthma. Fungal sensitization is also associated with earlier onset of asthma and demonstrates a dose-dependent relationship of symptom severity and duration. Among viruses, rhinovirus has the greatest association with decreased lung function, severe asthma, and asthma-related hospital admissions. Distribution of microbial products and associated asthma symptoms depends on the geographical climate. Genetic variations among individuals also mitigate the effects of microbial products on asthma development and symptom severity. SUMMARY: Microbial products of bacteria, fungi, and viruses are associated with the development of asthma, more severe asthma symptoms, and worse outcomes. However, some early exposure studies have also demonstrated a protective effect. Bacterial and fungal products are related to decreased lung function and earlier onset of asthma. Viral products are related to asthma-associated hospital admissions; and the climate and patient genetics can also temper or intensify the relationships between microbial products, asthma development, and asthma symptom severity. Further research should focus on the effects of early microbe exposure and its interaction with human immune systems and asthma-related outcomes.


title: Effective inhibition of porcine epidemic diarrhea virus by RNA interference in vitro

text: Porcine epidemic diarrhea virus (PEDV) is a member of the coronaviridae family, which can cause acute and highly contagious enteric disease of swine characterized by severe entero-pathogenic diarrhea in piglets. Currently, the vaccines of PEDV are only partially effective and there is no specific drug available for treatment of PEDV infection. To exploit the possibility of using RNA interference (RNAi) as a strategy against PEDV infection, five shRNA-expressing plasmids targeting the N, M, and S genes of PEDV were constructed and transfected into Vero cells. The cytopathic effect and MTS assays demonstrated that two shRNAs (pSilencer4.1-M1 and pSilencer4.1-N) were capable of protecting cells against PEDV invasion with very high specificity and efficiency. The two shRNA expression plasmids were also able to inhibit the PEDV replication significantly, as shown by detection of virus titers (TCID(50)/mL). A real-time quantitative RT-PCR further confirmed that the amounts of viral RNAs in cell cultures pre-transfected with these two plasmids were reduced by 95.0 %. Our results suggest that RNAi might be a promising new strategy against PEDV infection.


Clean Care is Safer Care: a worldwide priority


title: Complex Genetic Architecture Underlies Regulation of Influenza-A-Virus-Specific Antibody Responses in the Collaborative Cross

text: Host genetic factors play a fundamental role in regulating humoral immunity to viral infection, including influenza A virus (IAV). Here, we utilize the Collaborative Cross (CC), a mouse genetic reference population, to study genetic regulation of variation in antibody response following IAV infection. CC mice show significant heritable variation in the magnitude, kinetics, and composition of IAV-specific antibody response. We map 23 genetic loci associated with this variation. Analysis of a subset of these loci finds that they broadly affect the antibody response to IAV as well as other viruses. Candidate genes are identified based on predicted variant consequences and haplotype-specific expression patterns, and several show overlap with genes identified in human mapping studies. These findings demonstrate that the host antibody response to IAV infection is under complex genetic control and highlight the utility of the CC in modeling and identifying genetic factors with translational relevance to human health and disease.


Coronavirus Disease 2019 (COVID‐19) and cardiac surgeon—Are we on the back foot?


Cancer and COVID-19; how do we manage cancer optimally through a public health crisis?


title: Type I Interferon Receptor Signaling of Neurons and Astrocytes Regulates Microglia Activation during Viral Encephalitis

text: In sterile neuroinflammation, a pathological role is proposed for microglia, whereas in viral encephalitis, their function is not entirely clear. Many viruses exploit the odorant system and enter the CNS via the olfactory bulb (OB). Upon intranasal vesicular stomatitis virus instillation, we show an accumulation of activated microglia and monocytes in the OB. Depletion of microglia during encephalitis results in enhanced virus spread and increased lethality. Activation, proliferation, and accumulation of microglia are regulated by type I IFN receptor signaling of neurons and astrocytes, but not of microglia. Morphological analysis of myeloid cells shows that type I IFN receptor signaling of neurons has a stronger impact on the activation of myeloid cells than of astrocytes. Thus, in the infected CNS, the cross talk among neurons, astrocytes, and microglia is critical for full microglia activation and protection from lethal encephalitis.


title: Mathematical Modeling of COVID-19 Control and Prevention Based on Immigration Population Data in China: Model Development and Validation

text: BACKGROUND: At the end of February 2020, the spread of coronavirus disease (COVID-19) in China had drastically slowed and appeared to be under control compared to the peak data in early February of that year. However, the outcomes of COVID-19 control and prevention measures varied between regions (ie, provinces and municipalities) in China; moreover, COVID-19 has become a global pandemic, and the spread of the disease has accelerated in countries outside China. OBJECTIVE: This study aimed to establish valid models to evaluate the effectiveness of COVID-19 control and prevention among various regions in China. These models also targeted regions with control and prevention problems by issuing immediate warnings. METHODS: We built a mathematical model, the Epidemic Risk Time Series Model, and used it to analyze two sets of data, including the daily COVID-19 incidence (ie, newly diagnosed cases) as well as the daily immigration population size. RESULTS: Based on the results of the model evaluation, some regions, such as Shanghai and Zhejiang, were successful in COVID-19 control and prevention, whereas other regions, such as Heilongjiang, yielded poor performance. The evaluation result was highly correlated with the basic reproduction number (R(0)) value, and the result was evaluated in a timely manner at the beginning of the disease outbreak. CONCLUSIONS: The Epidemic Risk Time Series Model was designed to evaluate the effectiveness of COVID-19 control and prevention in different regions in China based on analysis of immigration population data. Compared to other methods, such as R(0), this model enabled more prompt issue of early warnings. This model can be generalized and applied to other countries to evaluate their COVID-19 control and prevention.


title: Expression and functional analysis of porcine aminopeptidase N produced in prokaryotic expression system

text: Abstract Porcine aminopeptidase N (pAPN) is a cellular membrane protein and a functional receptor for porcine coronaviruses. Here, we describe the heterologous expression of pAPN without signal peptide in BL21(DE3)pLysS host cells. The Escherichia coli (E. coli) harboring the recombinant construct was efficiently induced to express the pAPN protein at a high level. The most optimal expression profile for pAPN expression was investigated. By inoculating a rabbit with the purified pAPN, a high tittered specific antibody was achieved. Biologically, the antibody reacted with either pAPN-expressing E. coli or native pAPN on the surface of swine testis cells. The pAPN and its specific antibody blocked transmissible gastroenteritis coronavirus infection in vitro. Furthermore, the localization of pAPN on the small intestine of swine was analyzed by immunohistochemistry.


title: Foxp3(+) regulatory T cells, immune stimulation and host defence against infection

text: The immune system is intricately regulated allowing potent effectors to expand and become rapidly mobilized after infection, while simultaneously silencing potentially detrimental responses that averts immune-mediated damage to host tissues. This relies in large part on the delicate interplay between immune suppressive regulatory CD4(+) T (Treg) cells and immune effectors that without active suppression by Treg cells cause systemic and organ-specific autoimmunity. Although these beneficial roles have been classically described as counterbalanced by impaired host defence against infection, newfound protective roles for Treg cells against specific viral pathogens (e.g. herpes simplex virus 2, lymphocytic choriomeningitis virus, West Nile virus) have been uncovered using transgenic mice that allow in vivo Treg-cell ablation based on Foxp3 expression. In turn, Foxp3(+) Treg cells also provide protection against some parasitic (Plasmodium sp., Toxoplasma gondii) and fungal (Candida albicans) pathogens. By contrast, for bacterial and mycobacterial infections (e.g. Listeria monocytogenes, Salmonella enterica, Mycobacterium tuberculosis), experimental manipulation of Foxp3(+) cells continues to indicate detrimental roles for Treg cells in host defence. This variance is probably related to functional plasticity in Treg cell suppression that shifts discordantly following infection with different types of pathogens. Furthermore, the efficiency whereby Treg cells silence immune activation coupled with the plasticity in Foxp3(+) cell activity suggest that overriding Treg-mediated suppression represents a prerequisite ‘signal zero’ that together with other stimulation signals [T-cell receptor (signal 1), co-stimulation (signal 2), inflammatory cytokines (signal 3)] are essential for T-cell activation in vivo. Herein, the importance of Foxp3(+) Treg cells in host defence against infection, and the significance of infection-induced shifts in Treg-cell suppression are summarized.


Curcumin: a Wonder Drug as a Preventive Measure for COVID19 Management


title: Performance Evaluation of the Maxwell 16 System for Extraction of Influenza Virus RNA from Diverse Samples

text: This study evaluated the performance of the Maxwell 16 System (Promega) for extraction of influenza virus (flu-v) RNA from diverse samples compared to a classical manual method (QIAamp Kit, QIAGEN). Following extraction by the two methods, all samples were analyzed by Real-time RT-PCR. Results revealed that the use of the standard Maxwell 16 protocol (Maxwell 16-S) resulted in good linearity and precision across a wide concentration range and higher sensitivity of detection from flu-v stock suspensions than the manual method. Compared with the latter method, Maxwell 16-S extracted RNA more efficiently (higher RNA yield and/or fewer PCR inhibitors) from throat swabs and bronchoalveolar lavage fluids, while both methods performed comparably on fecal samples from human and poultry in terms of overall threshold cycle values and detection rates although the Maxwell 16-S co-purified more inhibitors from fecal samples. The capacity of this system to remove inhibitors from fecal matrix was improved by using a modified Maxwell 16 protocol with a reduced sample input, which eliminated all false-negatives produced by the Maxwell 16-S. These findings suggest that the Maxwell 16 System is suitable for RNA extraction from multiple-source samples for diagnosis of influenza and viral load determination and that a proper reduction in starting sample volume may improve the detection of flu-v from complex matrices such as feces. Additionally, this system allows flexible sample throughput and labor-saving sample processing with little or no risk of cross-contamination.


title: Networking for training Level 3/4 biosafety laboratory staff

text: Abstract Worldwide, public health systems are continually challenged by emerging and re-emerging viruses. It is therefore important that high-containment labs coordinate and communicate globally to share their experiences and lessons to improve their capacity to respond to threats. The National Biosafety (Level 4) Laboratory in Wuhan, CAS, which is the first Level 4 biosafety laboratory (BSL-4) in China, has been certified recently and it is expected to play an important role in the prevention and control of highly infectious agents in future. Trained and experienced staff in such organizations is the most important factor contributing to safety and security. Therefore, it is imperative to develop a standard training program. Accordingly, in the present study, we developed an improved training program and assessment system based on policies and practices developed by BSL-3/4s in other countries. It included the following three components: (1) A flexible modularized theoretical training: This training comprised 14 modularized theoretical topics such that staffs with different backgrounds could take this theoretical training with different topic combinations according to their knowledge and skill levels; (2) A standardized practical training assessment: This comprehensive assessment, which could be used with biosafety laboratory staff before, during, and after training, included standard operation procedures to meet the special requirements of trainees with different scores; and (3) An applicable documentation system: A certification system was established to evaluate the ability of all staff working inside or outside the laboratory, implemented by a special committee. This certification was approved and authorized by the director of the laboratory and was classified into three grades with corresponding minimal requirements. Further, the present study examined the importance of and need for networking for training BSL-3/4 staff. The establishment of rigorous standards for training BSL-3/4 staff will instill confidence in the public, policy makers, and security officials. Additionally, the expanded international network of BSL-3/4s will continue to be operated safely and will pose no risk to scientific staff, local communities, surrounding environment, and host nations. The clarification and coordination of training standards will help develop a highly-qualified biocontainment workforce and will result in a series of programs that will enable scientists to develop measures to deal with existing threat agents and new diseases that emerge.


title: Metabolic liver disease in diabetes – from mechanisms to clinical trials

text: Abstract Non-alcoholic fatty liver disease (NAFLD) comprises fatty liver (steatosis), non-alcoholic steatohepatitis (NASH) and fibrosis/cirrhosis and may lead to end-stage liver failure or hepatocellular carcinoma. NAFLD is tightly associated with the most frequent metabolic disorders, such as obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). Both multisystem diseases share several common mechanisms. Alterations of tissue communications include excessive lipid and later cytokine release by dysfunctional adipose tissue, intestinal dysbiosis and ectopic fat deposition in skeletal muscle. On the hepatocellular level, this leads to insulin resistance due to abnormal lipid handling and mitochondrial function. Over time, cellular oxidative stress and activation of inflammatory pathways, again supported by multiorgan crosstalk, determine NAFLD progression. Recent studies show that particularly the severe insulin resistant diabetes (SIRD) subgroup (cluster) associates with NAFLD and its accelerated progression and increases the risk of diabetes-related cardiovascular and kidney diseases, underpinning the critical role of insulin resistance. Consequently, lifestyle modification and certain drug classes used to treat T2DM have demonstrated effectiveness for treating NAFLD, but also some novel therapeutic concepts may be beneficial for both NAFLD and T2DM. This review addresses the bidirectional relationship between mechanisms underlying T2DM and NAFLD, the relevance of novel biomarkers for improving the diagnostic modalities and the identification of subgroups at specific risk of disease progression. Also, the role of metabolism-related drugs in NAFLD is discussed in light of the recent clinical trials. Finally, this review highlights some challenges to be addressed by future studies on NAFLD in the context of T2DM.


title: Abnormal glycogen in astrocytes is sufficient to cause adult polyglucosan body disease

text: Abstract Background A 45-year old woman of Cambodian ethnic background presented with fatal respiratory failure due to a severe diaphragmatic dysfunction. Two years before, she had developed early onset of urinary symptoms. Methods and results Neuroimaging showed atrophy of the spine and medulla as well as a leukodystrophy affecting both supra- and infra-tentorial regions. At autopsy, polyglucosan bodies (PB) were seen in several peripheral tissues, including the diaphragm, and nervous tissues such as peripheral nerves, cerebral white matter, basal ganglia, hippocampus, brainstem and cerebellum. Immunohistochemistry and electron microscopy of the brain revealed an exclusive astrocytic localization of the PB. The diagnosis of adult polyglucosan body disease (APBD) was confirmed by enzymatic and molecular studies. Conclusion Storage of abnormal glycogen in astrocytes is sufficient to cause the leukodystrophy of APBD. Since brain glycogen is almost exclusively metabolized in astrocytes, this observation sheds light on the pathophysiology of APBD. In addition, this is the first report of an APBD patient presenting with a subacute diaphragmatic failure.


title: To translate, or not to translate: viral and host mRNA regulation by interferon-stimulated genes

text: Type I interferon (IFN) is one of the first lines of cellular defense against viral pathogens. As a result of IFN signaling, a wide array of IFN-stimulated gene (ISG) products is upregulated to target different stages of the viral life cycle. We review recent findings implicating a subset of ISGs in translational regulation of viral and host mRNAs. Translation inhibition is mediated either by binding to viral RNA or by disrupting physiological interactions or levels of the translation complex components. In addition, many of these ISGs localize to translationally silent cytoplasmic granules, such as stress granules and processing bodies, and intersect with the microRNA (miRNA)-mediated silencing pathway to regulate translation of cellular mRNAs.


title: Rapid and sensitive detection of canine distemper virus by real-time reverse transcription recombinase polymerase amplification

text: BACKGROUND: Canine distemper, caused by Canine distemper virus (CDV), is a highly contagious and fatal systemic disease in free-living and captive carnivores worldwide. Recombinase polymerase amplification (RPA), as an isothermal gene amplification technique, has been explored for the molecular detection of diverse pathogens. METHODS: A real-time reverse transcription RPA (RT-RPA) assay for the detection of canine distemper virus (CDV) using primers and exo probe targeting the CDV nucleocapsid protein gene was developed. A series of other viruses were tested by the RT-RPA.Thirty-two field samples were further tested by RT-RPA, and the resuts were compared with those obtained by the real-time RT-PCR. RESULTS: The RT-RPA assay was performed successfully at 40 °C, and the results were obtained within 3 min–12 min. The assay could detect CDV, but did not show cross-detection of canine parvovirus-2 (CPV-2), canine coronavirus (CCoV), canine parainfluenza virus (CPIV), pseudorabies virus (PRV) or Newcastle disease virus (NDV), demonstrating high specificity. The analytical sensitivity of RT-RPA was 31.8 copies in vitro transcribed CDV RNA, which is 10 times lower than the real-time RT-PCR. The assay performance was validated by testing 32 field samples and compared to real-time RT-PCR. The results indicated an excellent correlation between RT-RPA and a reference real-time RT-PCR method. Both assays provided the same results, and R(2) value of the positive results was 0.947. CONCLUSIONS: The results demonstrated that the RT-RPA assay offers an alternative tool for simple, rapid, and reliable detection of CDV both in the laboratory and point-of-care facility, especially in the resource-limited settings.


Author's Reply


title: Stroke as a complication and prognostic factor of COVID-19

text: Abstract Introduction Contradictory data have been reported on the incidence of stroke in patients with COVID-19 and the risk of SARS-CoV-2 infection among patients with history of stroke. Methods This study systematically reviews case series reporting stroke as a complication of COVID-19, and analyses the prognosis of patients with COVID-19 and history of stroke. The pathophysiological mechanisms of stroke in patients with COVID-19 are also reviewed. Conclusions History of stroke increases the risk of death due to COVID-19 by 3 times. Stroke currently seems not to be one of the main complications of COVID-19.


title: The IMEx Coronavirus interactome: an evolving map of Coronaviridae-Host molecular interactions

text: The current Coronavirus Disease 2019 (COVID-19) pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has spurred a wave of research of nearly unprecedented scale. Among the different strategies that are being used to understand the disease and develop effective treatments, the study of physical molecular interactions enables studying fine-grained resolution of the mechanisms behind the virus biology and the human organism response. Here we present a curated dataset of physical molecular interactions, manually extracted by IMEx Consortium curators focused on proteins from SARS-CoV-2, SARS-CoV-1 and other members of the Coronaviridae family. Currently, the dataset comprises over 2,200 binarized interactions extracted from 86 publications. The dataset can be accessed in the standard formats recommended by the Proteomics Standards Initiative (HUPO-PSI) at the IntAct database website (www.ebi.ac.uk/intact), and will be continuously updated as research on COVID-19 progresses.


title: Population-based Post-crisis Psychological Distress: An Example From the SARS Outbreak in Taiwan

text: Background/Purpose As a result of the severe acute respiratory syndrome (SARS) pandemic, the World Health Organization placed Taiwan on the travel alert list from May 21 to July 5, 2003. The aim of this study was to explore the post-crisis psychological distress among residents in Taiwan after the SARS epidemic. Methods The target population consisted of a nationwide representative sample of residents aged ≥ 18 years. Data were collected using computer assisted telephone interview systems by stratified random sampling according to geographic area. The survey (n = 1278) was conducted in November 2003, about 4 months after resolution of the SARS crisis in Taiwan. The maximum deviation of sampling error at the 95% confidence level was ± 2.74%. Psychological distress was measured by a question related to subject's changes in perception of life, plus the five-item Brief Symptom Rating Scale. Multivariate logistic regression was used to examine the correlation of psychological distress. Results About 9.2% of the participants reported that their perceptions of life became more pessimistic following the SARS crisis. The prevalence of psychiatric morbidity was 11.7%. Major predictors of higher levels of pessimism after the SARS epidemic included demographic factors, perception of SARS and preparedness, knowing people or having personal experiences of SARS-related discrimination, and individual worries and psychiatric morbidity. The correlates of symptomatic cases, as indicated by the five-item Brief Symptom Rating Scale, included age ≥ 50 years, senior high school graduate, and worries about recurrence of SARS. Conclusion Psychological distress was significantly correlated with demographic factors and perception regarding the SARS epidemic. It is suggested that marketing of mental health education should be segmented according to age and education level, which should enhance crisis communication for newly emerging infectious diseases among community populations.


title: One-step real-time reverse transcription-PCR assays for detecting and subtyping pandemic influenza A/H1N1 2009, seasonal influenza A/H1N1, and seasonal influenza A/H3N2 viruses

text: Abstract Pandemic influenza A/H1N1 2009 (A/H1N1pdm) virus has caused significant outbreaks worldwide. A previous one-step real-time reverse transcription-PCR (rRT-PCR) assay for detecting A/H1N1pdm virus (H1pdm rRT-PCR assay) was improved since the former probe had a low melting temperature and low tolerance to viral mutation. To help with the screening of the A/H1N1pdm virus, rRT-PCR assays were also developed for detecting human seasonal A/H1N1 (H1 rRT-PCR assay) and A/H3N2 influenza viruses (H3 rRT-PCR assay). H1pdm, H1, and H3 rRT-PCR assays were evaluated using in vitro-transcribed control RNA, isolated viruses, and other respiratory pathogenic viruses, and were shown to have high sensitivity, good linearity (R 2 =0.99), and high specificity. In addition, the improved H1pdm rRT-PCR assay could detect two viral strains of A/H1N1pdm, namely, A/Aichi/472/2009 (H1N1)pdm and A/Sakai/89/2009 (H1N1)pdm, which have mutation(s) in the probe-binding region of the hemagglutinin gene, without loss of sensitivity. Using the three rRT-PCR assays developed, 90 clinical specimens collected between May and October 2009 were then tested. Of these, 26, 20, and 2 samples were identified as positive for A/H1pdm, A/H3, and A/H1, respectively, while 42 samples were negative for influenza A viruses. The present results suggest that these highly sensitive and specific H1pdm, H1, and H3 rRT-PCR assays are useful not only for diagnosing influenza viruses, but also for the surveillance of influenza viruses.


New clinical needs and strategies for care in children with neurodisability during COVID‐19


title: Macroeconomic and health care aspects of the coronavirus epidemic: EU, US and global perspectives

text: The novel coronavirus (COVID-19) epidemic represents a major challenge for the world economy. While a detailed longer-term diffusion path of the new virus cannot be anticipated for individual countries, one may anticipate international supply shocks and declining GDP growth in many OECD countries and China in 2020; and one should expect falling asset prices in Asia, the United States and the European Union plus the United Kingdom – except for the price of risk-free government bonds. In the course of 2020/21 the US, the EU and the UK, as well as other countries, will face both an increasing number of infected patients as well as a higher case fatality ratio. Health care expenditures in the US could increase more than in the Eurozone and the EU in the medium term, a development that undermines the international competitiveness of the United States. The analysis suggests that per capita income is a positive function of the effective trade openness and of the new Global Health Security Index indicator from the NTI/Johns Hopkins University. A rising health care-GDP ratio in the US is equivalent to a rising US export tariff. As regards the coronavirus challenge, the ratio of acute care beds to the elderly in OECD countries shows considerable variation. Due to international tourism contraction alone, output growth in the Eurozone, the US and China can be expected to fall by about 1.6% in 2020. The COVID-19 challenge for the US Trump Administration is a serious one, since the lack of experts in the Administration will become more apparent in such a systemic stress situation – and this might well affect the November 2020 US presidential election which, in turn, would itself have considerable impacts on the UK and the EU27 as well as EU-UK trade negotiations. Integrating the health care sector into macroeconomics, which should include growth analysis, is an important task. The role of health quality - and health insurance coverage - for endogenous time horizons and economic welfare, respectively, is emphasized.


title: M and N proteins of SARS coronavirus induce apoptosis in HPF cells

text: Background: SARS-associated coronavirus (SARS-CoV) induced cell apoptosis and its structural proteins may play a role in this process. Objectives: To determine whether the structural proteins M and N of SARS-CoV induce apoptosis. Study design: We investigated human pulmonary fibroblast (HPF) cells, were transfected with plasmids containing the M or N gene, by TdT-mediated dUTP nick end labeling (TUNEL), Hoechst 33342 staining for nuclei, and observation of morphology. Results: We found that in the absence of serum about 16.34% of cells transfected by pcDNA3.1-M and 21.72% of N-transfected cells showed typical apoptotic characteristics, significantly different from mock-transfected cells (only 6.23%, p<0.01). Furthermore, the cells that were co-transfected with M and N proteins showed more obvious phenomena of cell death (about 36.03%). There was a statistical significance between M-transfected cells and co-transfected cells (p<0.01), and a remarkable difference between N-transfected cells and co-transfected cells (p<0.01). Conclusions: The results show that M and N proteins of SARS-CoV can induce apoptosis of HPF cells. Co-transfection of M and N enhances the induction of apoptosis by M or N alone, which also suggests that the structural proteins of SARS-CoV may play an important role not only in the process of invasion but also in the pathogenetic process in cells.


title: Potential impact of COVID-19 on colorectal disease management

text: Abstract The current recommendations for management of colorectal diseases are still evolving, due to the limited experience on this issue. As the new coronavirus can be transmitted through breath droplets, by contact and orofecally, there is no consensus of how this fact may affect the investigation and treatment of anorectal diseases. Thus, high-quality multicenter studies are urgently needed to provide better information to both patients and the multiprofessional team, in order to build an effective pandemic response plan in our specialty. As a greater operative risk for infected patients has already been demonstrated, the next step lies on the identification of new therapeutic strategies that could minimize this effect on an individual basis. There is a present understanding that the COVID-19 pandemic should change some traditional practices. Therefore, the surgical treatment of suspected or known COVID-19 case demands specific insights. This article analyses potential influences regarding the treatment of patients with Colorectal Cancer (CRC) and Inflammatory Bowel Diseases (IBD). At present, elective surgery must be avoided, and the colorectal surgeon must carefully evaluate the risks and benefits of such decision. Within this context, a change towards nonsurgical and less aggressive modalities of CRC treatment may help to postpone definitive treatment. We also discuss the concerns regarding the viral infection among the IBD population, the influence on clinical symptoms and the proposed modifications on therapeutic schemes.


title: In toxic demyelination oligodendroglial cell death occurs early and is FAS independent

text: Abstract Oligodendroglial cell death is a frequent phenomenon of many neurological diseases, e.g. in demyelinating diseases such as multiple sclerosis (MS). The underlying mechanisms are largely unknown. Here, we demonstrate that in the toxic demyelination cuprizone model, oligodendroglial cell death and downregulation of myelin genes start days after initiation of the cuprizone diet and weeks before demyelination is obvious. In early – but not in later – stages, dying oligodendrocytes express activated caspase 3, suggesting a switch from classical apoptotic pathways to caspase 3-independent mechanisms during the course of the cuprizone diet. The expression level of FAS in the corpus callosum, a cell death receptor crucial for oligodendroglial cell death in experimental autoimmune encephalomyelitis (EAE), correlates with the expression of activated caspase 3 in oligodendrocytes. However, mice lacking FAS in oligodendrocytes are not protected against cuprizone-induced oligodendroglial cell death, showing that FAS is dispensable for oligodendroglial cell death in the cuprizone model.


title: Trade, production sharing, and the international transmission of business cycles

text: Abstract Countries that are more engaged in production sharing exhibit higher bilateral manufacturing output correlations. We use data on trade flows between US multinationals and their affiliates as well as trade between the United States and Mexican maquiladoras to measure production-sharing trade and its link with the business cycle. We then develop a quantitative model of international business cycles that generates a positive link between the extent of vertically integrated production-sharing trade and internationally synchronized business cycles. A key assumption in the model is a relatively low elasticity of substitution between home and foreign inputs in the production of the vertically integrated good.


title: Successful COVID-19 rescue therapy by extra-corporeal membrane oxygenation (ECMO) for respiratory failure: a case report

text: BACKGROUND: The value of extracorporeal membrane oxygenation (ECMO) for patients suffering from novel coronavirus disease 2019 (COVID-19) as a rescue therapy for respiratory failure remains controversial and associated with high mortality rates of 50 to 82% in early reports from Wuhan, China. We hypothesized that patient outcomes would be improved at our tertiary cardiothoracic surgery referral center with a protocolized team-approach for ECMO treatment of patients with severe COVID-19 disease. CASE PRESENTATION: A 51-year-old healthy female developed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) bilateral pneumonia while vacationing in Colorado with her family. She was transferred to our facility for a higher level of care. Her respiratory status continued to deteriorate despite maximized critical care, including prone positioning ventilation and nitric oxide inhalation therapy. Veno-venous ECMO was initiated on hospital day 7 in conjunction with a 10-day course of compassionate use antiviral treatment with remdesivir. The patient’s condition improved significantly and she was decannulated from ECMO on hospital day 17 (ECMO day 11). She was successfully extubated and eventually discharged to rehabilitation on hospital day 28. CONCLUSION: This case report demonstrates a positive outcome in a young patient with COVID-19 treated by the judicious application of ECMO in conjunction with compassionate use antiviral treatment (remdesivir). Future prospective multi-center studies are needed to validate these findings in a larger cohort of patients.


title: Spike-based phylogenetically defined clades within the Alphacoronavirus 1 species

text: Taxonomic classification for the Coronaviridae can be challenging, due to the wide host tropism and highly variable genome of the viruses in this Family. Within the Alphacoronavirus genus, there is a single species Alphacoronavirus 1 that encompasses several biologically distinct viruses of distinct animal species. Here, we carried out phylogenetic analysis of members of the Alphacoronavirus genus, focusing on the viral spike gene, which is a primary driver of viral tropism and pathogenesis. We identify two distinct clades (A and B) within the Alphacoronavirus 1 species. Alphacoronavirus 1 clade A encompasses serotype I FCoV and CCoV, and Alphacoronavirus 1 clade B, encompasses serotype II FCoV and CCoV and TGEV-like viruses. We propose this clade designation, along with the newly proposed Alphacoronavirus 2 species, as an improved way to classify the diverse Alphacoronavirus genus.


title: Benefits of Intensive Care Unit Hospitalization for Patients Older than 90 Years

text: This editorial comments on the article by Haas et al.


title: Impact of the Interaction of Hepatitis B Virus with Mitochondria and Associated Proteins

text: Around 350 million people are living with hepatitis B virus (HBV), which can lead to death due to liver cirrhosis and hepatocellular carcinoma (HCC). Various antiviral drugs/nucleot(s)ide analogues are currently used to reduce or arrest the replication of this virus. However, many studies have reported that nucleot(s)ide analogue-resistant HBV is circulating. Cellular signaling pathways could be one of the targets against the viral replication. Several studies reported that viral proteins interacted with mitochondrial proteins and localized in the mitochondria, the powerhouse of the cell. And a recent study showed that mitochondrial turnover induced by thyroid hormones protected hepatocytes from hepatocarcinogenesis mediated by HBV. Strong downregulation of numerous cellular signaling pathways has also been reported to be accompanied by profound mitochondrial alteration, as confirmed by transcriptome profiling of HBV-specific CD8 T cells from chronic and acute HBV patients. In this review, we summarize the ongoing research into mitochondrial proteins and/or signaling involved with HBV proteins, which will continue to provide insight into the relationship between mitochondria and HBV and ultimately lead to advances in viral pathobiology and mitochondria-targeted antiviral therapy.


title: Porcine epidemic diarrhea virus: An emerging and re-emerging epizootic swine virus

text: The enteric disease of swine recognized in the early 1970s in Europe was initially described as “epidemic viral diarrhea” and is now termed “porcine epidemic diarrhea (PED)”. The coronavirus referred to as PED virus (PEDV) was determined to be the etiologic agent of this disease in the late 1970s. Since then the disease has been reported in Europe and Asia, but the most severe outbreaks have occurred predominantly in Asian swine-producing countries. Most recently, PED first emerged in early 2013 in the United States that caused high morbidity and mortality associated with PED, remarkably affecting US pig production, and spread further to Canada and Mexico. Soon thereafter, large-scale PED epidemics recurred through the pork industry in South Korea, Japan, and Taiwan. These recent outbreaks and global re-emergence of PED require urgent attention and deeper understanding of PEDV biology and pathogenic mechanisms. This paper highlights the current knowledge of molecular epidemiology, diagnosis, and pathogenesis of PEDV, as well as prevention and control measures against PEDV infection. More information about the virus and the disease is still necessary for the development of effective vaccines and control strategies. It is hoped that this review will stimulate further basic and applied studies and encourage collaboration among producers, researchers, and swine veterinarians to provide answers that improve our understanding of PEDV and PED in an effort to eliminate this economically significant viral disease, which emerged or re-emerged worldwide.


title: Inpatient Capacity at Children’s Hospitals during Pandemic (H1N1) 2009 Outbreak, United States

text: Quantifying how close hospitals came to exhausting capacity during the outbreak of pandemic influenza A (H1N1) 2009 can help the health care system plan for more virulent pandemics. This ecologic analysis used emergency department (ED) and inpatient data from 34 US children's hospitals. For the 11-week pandemic (H1N1) 2009 period during fall 2009, inpatient occupancy reached 95%, which was lower than the 101% occupancy during the 2008-09 seasonal influenza period. Fewer than 1 additional admission per 10 inpatient beds would have caused hospitals to reach 100% occupancy. Using parameters based on historical precedent, we built 5 models projecting inpatient occupancy, varying the ED visit numbers and admission rate for influenza-related ED visits. The 5 scenarios projected median occupancy as high as 132% of capacity. The pandemic did not exhaust inpatient bed capacity, but a more virulent pandemic has the potential to push children's hospitals past their maximum inpatient capacity.


title: Astrovirus in wild boars (Sus scrofa) in Hungary

text: The family Astroviridae consists of two genera, Avastrovirus and Mamastrovirus whose members are associated with gastroenteritis in avian and mammalian hosts, respectively. In this study, we report the first detection of astrovirus from fecal specimens of wild boars (Sus scrofa) using viral metagenomics and complete genome sequencing. The wild boar astrovirus (WBAstV-1/2011/HUN, JQ340310) genome is 6707 nucleotide long and had 76%, 95% and 56% amino acid (aa) identity in the ORF1a (852aa), ORF1b (522aa) and ORF2 (845aa) regions, respectively, to porcine astrovirus 4 (PAstV-4, JF713713), the closest match. This study indicates that wild boar could be a reservoir for astroviruses.


Airway Management in COVID-19: In the Den of the Beast


Dapsone and Doxycycline could be potential treatment modalities for COVID-19


Covid-19: Impact on Perianesthesia Nursing Areas


title: A programmable CRISPR/Cas9-based phage defense system for Escherichia coli BL21(DE3)

text: Escherichia coli BL21 is arguably the most popular host for industrial production of proteins, and industrial fermentations are often plagued by phage infections. The CRISPR/Cas system is guided by a gRNA to cleave a specific DNA cassette, which can be developed into a highly efficient programable phage defense system. In this work, we constructed a CRISPR/Cas system targeting multiple positions on the genome of T7 phage and found that the system increased the BL21’s defense ability against phage infection. Furthermore, the targeted loci on phage genome played a critical role. For better control of expression of CRISPR/Cas9, various modes were tested, and the OD of the optimized strain BL21(pT7cas9, pT7-3gRNA, prfp) after 4 h of phage infection was significantly improved, reaching 2.0, which was similar to the control culture without phage infection. Although at later time points, the defensive ability of CRISPR/Cas9 systems were not as obvious as that at early time points. The viable cell count of the engineered strain in the presence of phage was only one order of magnitude lower than that of the strain with no infection, which further demonstrated the effectiveness of the CRISPR/Cas9 phage defense system. Finally, the engineered BL21 strain under phage attack expressed RFP protein at about 60% of the un-infected control, which was significantly higher than the parent BL21. In this work, we successfully constructed a programable CRISPR/Cas9 system to increase the ability of E. coli BL21’s to defend against phage infection, and created a resistant protein expression host. This work provides a simple and feasible strategy for protecting industrial E. coli strains against phage infection.


title: Outbreak of Middle East Respiratory Syndrome-Coronavirus Causes High Fatality After Cardiac Operations

text: Middle East respiratory syndrome-coronavirus (MERS-CoV) resembles a severe form of community-acquired pneumonia initially reported in Saudi Arabia in 2012. The MERS-CoV epidemic poses a big challenge because of its high mortality. In January 2015, a patient who was potentially incubating MERS-CoV arrived from the emergency department of another hospital and was admitted with acute coronary syndrome. This resulted in an outbreak in the cardiac surgery ward that caused the deaths of 5 of 6 patients who had undergone cardiac operations.


title: Advancing scientific knowledge in times of pandemics

text: Researchers at the Precision Immunology Institute at the Icahn School of Medicine (PrIISM), New York, describe their contribution to the global research effort against COVID-19 by trying to separate signal from noise in the preprint arena.


title: Antiviral effects on bacteriophages and rotavirus by cranberry juice

text: Abstract Studies were undertaken to investigate the antiviral effects of comestible juices, especially cranberry juice, on non-related viral species. After exposure of bacteriophage T2 to a commercially available cranberry (Vaccinium macrocarpon) juice cocktail (CJ), virus infectivity titer was no longer detectible. After a 60-min exposure to orange (OJ) and grapefruit juices (GJ), phage infectivity was reduced to 25–35% of control, respectively. Similar data were observed for the bacteriophage T4. CJ inactivation of phage T4 was rapid, dose-dependent, and occurred at either 4 or 23°C. Neither pH nor differences in sugar/carbohydrate levels among the juices may be ascribed to the recognized antiviral effects. Further studies were performed to identify the occurrence of antiviral activity by CJ to a mammalian enteric virus. The treatment of the simian rotavirus SA-11 with a 20% CJ suspension was sufficient to inhibit hemagglutination. Under scanning and transmission electron microscopy, CJ was observed to inhibit the adsorption of phage T4 to its bacterial host cells and prevented the replication of rotavirus in its monkey kidney (MA-104) host cells, respectively. The data suggest, for the first time, a non-specific antiviral effect towards unrelated viral species (viz., bacteriophages T2 and T4 and the simian rotavirus SA-11) by a commercially available cranberry fruit juice drink.


title: Development of a Selection Method for Discovering Irreversible (Covalent) Binders from a DNA-Encoded Library

text: DNA-encoded libraries (DELs) have been broadly applied to identify chemical probes for target validation and lead discovery. To date, the main application of the DEL platform has been the identification of reversible ligands using multiple rounds of affinity selection. Irreversible (covalent) inhibition offers a unique mechanism of action for drug discovery research. In this study, we report a developing method of identifying irreversible (covalent) ligands from DELs. The new method was validated by using 3C protease (3CP) and on-DNA irreversible tool compounds (rupintrivir derivatives) spiked into a library at the same concentration as individual members of that library. After affinity selections against 3CP, the irreversible tool compounds were specifically enriched compared with the library members. In addition, we compared two immobilization methods and concluded that microscale columns packed with the appropriate affinity resin gave higher tool compound recovery than magnetic beads.


Management of COVID-19 in burns patients: The experience of a UK burn centre


SARS‐CoV‐2, the medical profession, ventilator beds, and mortality predictions: personal reflections of an Australian clinician


title: Covid-19 epidemic in Italy: evolution, projections and impact of government measures

text: We report on the Covid-19 epidemic in Italy in relation to the extraordinary measures implemented by the Italian Government between the 24th of February and the 12th of March. We analysed the Covid-19 cumulative incidence (CI) using data from the 1st to the 31st of March. We estimated that in Lombardy, the worst hit region in Italy, the observed Covid-19 CI diverged towards values lower than the ones expected in the absence of government measures approximately 7–10 days after the measures implementation. The Covid-19 CI growth rate peaked in Lombardy the 22nd of March and in other regions between the 24th and the 27th of March. The CI growth rate peaked in 87 out of 107 Italian provinces on average 13.6 days after the measures implementation. We projected that the CI growth rate in Lombardy should substantially slow by mid-May 2020. Other regions should follow a similar pattern. Our projections assume that the government measures will remain in place during this period. The evolution of the epidemic in different Italian regions suggests that the earlier the measures were taken in relation to the stage of the epidemic, the lower the total cumulative incidence achieved during this epidemic wave. Our analyses suggest that the government measures slowed and eventually reduced the Covid-19 CI growth where the epidemic had already reached high levels by mid-March (Lombardy, Emilia-Romagna and Veneto) and prevented the rise of the epidemic in regions of central and southern Italy where the epidemic was at an earlier stage in mid-March to reach the high levels already present in northern regions. As several governments indicate that their aim is to “push down” the epidemic curve, the evolution of the epidemic in Italy supports the WHO recommendation that strict containment measures should be introduced as early as possible in the epidemic curve.


title: Pentraxin 3 as a clinical marker in children with lower respiratory tract infection

text: BACKGROUND: Pentraxin 3 (PTX‐3) is an acute‐phase protein that increases in the plasma during inflammation. OBJECTIVE: We aimed to evaluate the usefulness of PTX‐3 as a clinical marker in children with lower respiratory tract infection (LRTI) and examine the correlation of PTX‐3 with other biomarkers such as C‐reactive protein (CRP) and procalcitonin (PCT). METHODS: We enrolled 117 consecutive patients admitted to Seoul St. Mary's Hospital with LRTI using the WHO criteria. We recorded data on fever duration and peak temperature before admission, duration of fever after admission, respiratory rate, heart rate, oxygen saturation upon admission, duration of oxygen supplementation, and duration of hospital stay. Upon admission, white blood cell (WBC) count, erythrocyte sedimentation rate, CRP level were measured. Multiplex respiratory virus polymerase chain reaction was performed using nasal swabs. PTX‐3, PCT, and various cytokines were measured after the study had been completed. RESULTS: We found that there was no significant difference in the level of PTX‐3 according to the type of viral infection. PTX‐3 levels showed a significant correlation with PCT levels, but not with levels of CRP. The level of PTX‐3 showed a significant correlation with peak temperature and duration of fever before admission as well as interleukin (IL)‐6 levels. PCT levels showed a significant correlation with IL‐6 and granulocyte‐colony stimulating factor levels, peak temperature, and duration of fever before admission, and duration of hospital stay. CRP levels showed a significant correlation with duration of fever before admission, total WBC count, and neutrophil count. PCT levels significantly predicted a hospital stay of 7 days or more. PTX‐3, PCT, and CRP levels showed no correlation with any other clinical features. CONCLUSION: PTX‐3 reflected disease severity but failed to predict length of hospital stay. Further studies evaluating the use of PTX‐3 as a biomarker in mild LRTI would be useful. Pediatr Pulmonol. 2016;51:42–48. © 2015 Wiley Periodicals, Inc.


Twitter-based learning for continuing medical education?: A new perspective for a paradigm shift in medical education, accelerated by COVID-19


title: Evidence of porcine epidemic diarrhea virus (PEDV) shedding in semen from infected specific pathogen-free boars

text: In 2013, PED emerged for the first time in the United States (US). The porcine epidemic diarrhea virus (PEDV) spread quickly throughout North America. Infection with PEDV causes watery diarrhea and up to 100% mortality in piglets, particularly for highly pathogenic non-InDel strains circulating in the US. PEDV is mainly transmitted by the fecal–oral route. Transmission via the venereal route has been suspected but not previously investigated. The aim of the study was to determine if PEDV could be detected in semen from infected specific pathogen-free (SPF) boars inoculated with a PEDV US non-InDel strain suggesting venereal transmission may occur. Two boars orally inoculated with PEDV showed clinical signs and virus shedding in feces. Transient presence of the PEDV genome was detected by RT-qPCR in the seminal (5.06 × 10(2) to 2.44 × 10(3) genomic copies/mL) and sperm-rich fraction of semen (5.64 × 10(2) to 3.40 × 10(4) genomic copies/mL) and a longer duration of viral shedding was observed in the sperm-rich fraction. The evidence of PEDV shedding in semen raises new questions in term of disease spread within the pig population with the use of potentially contaminated semen.


title: Collective impacts on a global education emergency: The power of network response

text: The COVID-19 pandemic is an emergency of an exceptional scale, with major impacts on education globally and with significant new challenges for education in existing humanitarian contexts. This Viewpoint reflects on the immediate challenges of continuing education in humanitarian contexts and on the experience of the Inter-agency Network for Education in Emergencies (INEE) as a network supporting collective action of Education in Emergencies (EiE) practitioners globally. It also looks forward at INEE’s plans to support quality distance education and issues to consider on the reopening of schools. It concludes with reflections on the needs and risks for EiE longer term.


title: Ethics for surgeons during the COVID-19 pandemic, review article

text: The Covid-19 pandemic is a devastating global healthcare emergency with seismic impact on how modern surgical services function. Surgeons worry, that whilst healthcare-resources are directed against the pandemic, double effect may predict these benevolent public health efforts will cause unintended maleficent effects through delays to surgical treatment. Surgeons will make many challenging ethical judgements during this pandemic, here we conduct a narrative review of how medical ethics may help us make the best available choices. A narrative review of all the relevant papers known to the author was conducted. We discuss the key aspects of medical ethics, and how they have applied to surgeons during the Covid-19 pandemic. The four fundamental principles of medical ethics include: Beneficence, Nonmaleficence, Autonomy and Justice. Surgeons will face many decisions which shall challenge those ethical principles during the pandemic, and wisdom from medical ethics can guide surgeons, to do the right thing, make best available choices, and get the best available outcome for patients during the Covid-19 pandemic. The practice of surgery is distinguished by good judgement in the face of uncertainty, we must strive to do the right thing, advocate for our patients, and be honest in the face of uncertainty. Medical Ethics can guide us to make the best available choices for our patients during the Covid-19 pandemic, afterwards, we must emerge wiser having learnt lessons and rebuilding trust in surgical care.


title: Safety and efficacy of an infectious bronchitis virus used for chicken embryo vaccination

text: Commercial vaccines for in ovo vaccination have not yet been developed for infectious bronchitis virus (IBV), the major coronavirus in the poultry industry. Recombinant IBVs based on the Beaudette strain expressing the Beaudette spike protein (Beau-R) or that from the virulent M41 strain (BeauR-M41(S)) were assessed for their potential as prototype vaccines for application to 18-day-old embryos. Pathogenicity was assessed by observing the effect on hatchability, and/or the production of nasal discharge and/or the effects on ciliary activity in the trachea at various time points post hatch. In contrast to commercial IBV vaccines given in ovo, the Beau-R and BeauR-M41(S) strains did not reduce hatchability or cause nasal discharge, and caused minimal damage to the ciliated epithelium of the trachea. The presence of the spike protein from a virulent virus did not increase the pathogenicity of the virus according to the criteria used. Assessment of the BeauR-M41(S) strain for efficacy showed that it protected up to 90% of chicks against challenge with virulent IB virus (M41) in a dose dependent manner. Further egg passage of the BeauR-M41(S) strain (BeauR-M41(S) EP10) did not increase its pathogenicity though it did improve its efficacy, based on serology and protection against a virulent challenge. BeauR-M41(S) EP10 was more efficacious than BeauR-M41(S) protecting more birds against virulent challenge and providing a better serological antibody response. BeauR-M41(S) EP10 induced a serological response similar to that of a commercial vaccine given at day-old though the commercial vaccine provided slightly higher efficacy. These results are promising for the development of embryo safe efficacious IBV vaccines for in ovo application.


title: Lactobacillus acidophilus S-layer protein-mediated inhibition of PEDV-induced apoptosis of Vero cells

text: Abstract To gain insight into the mechanism of Lactobacillus acidophilus (L. acidophilus) S-layer protein antiviral activity, we examined how S-layer protein impacts porcine epidemic diarrhea virus (PEDV) infection and PEDV-induced apoptosis of Vero cells. Pretreatment (exclusion assay), coincubation (competition assay), and post-treatment (displacement assay) of PEDV-infected Vero cells with the S-layer protein was examined. Interestingly, significant inhibition of PEDV by S-layer protein was only observed in the exclusion assay. In Vero cells infected with PEDV, we found that apoptosis was mediated by activation of caspase-8 and caspase-3 in the late stage of infection. When PEDV-infected Vero cells were pretreated with S-layer protein, rates of Vero cell apoptosis were markedly decreased and cell damage was significantly reduced, as evaluated by flow cytometry and microscopy. Detailed analyses showed that the S-layer protein inhibited caspase-8 and caspase-3 activity. Taken together, our results suggest that L. acidophilus S-layer protein plays an inhibitory role during PEDV infection of Vero cells, and that the antagonistic activity of the protein is not via competition with PEDV for binding sites. In addition, the findings suggest that L. acidophilus S-layer protein protects against PEDV-induced apoptosis through reduced caspase-8 and caspase-3 activation in the later stages of infection. This mechanism may represent a novel approach for antagonizing PEDV and other viruses.


title: Engineered Human Cathelicidin Antimicrobial Peptides Inhibit Ebola Virus Infection

text: The 2014–2016 West Africa Ebola virus (EBOV) outbreak coupled with the most recent outbreaks in Central Africa underscore the need to develop effective treatment strategies against EBOV. Although several therapeutic options have shown great potential, developing a wider breadth of countermeasures would increase our efforts to combat the highly lethal EBOV. Here we show that human cathelicidin antimicrobial peptide (AMP) LL-37 and engineered LL-37 AMPs inhibit the infection of recombinant virus pseudotyped with EBOV glycoprotein (GP) and the wild-type EBOV. These AMPs target EBOV infection at the endosomal cell-entry step by impairing cathepsin B-mediated processing of EBOV GP. Furthermore, two engineered AMPs containing D-amino acids are particularly potent in blocking EBOV infection in comparison with other AMPs, most likely owing to their resistance to intracellular enzymatic degradation. Our results identify AMPs as a novel class of anti-EBOV therapeutics and demonstrate the feasibility of engineering AMPs for improved therapeutic efficacy.


title: The helicase activity of DDX56 is required for its role in assembly of infectious West Nile virus particles

text: Abstract Although flaviviruses encode their own helicases, evidence suggests that cellular helicases are also required for replication and/or assembly of these viruses. By and large, the mechanisms of action for viral and cellular helicases are not known. Moreover, in some cases, enzymatic activity is not even required for their roles in virus biology. Recently, we showed that expression of the host nucleolar helicase DDX56 is important for infectivity of West Nile virus (WNV) particles. In the present study, we demonstrate that the helicase activity of this enzyme is essential for its role in assembly of infectious WNV virions. Over-expression of the capsid-binding region of DDX56 also reduces infectivity of WNV suggesting that interaction of DDX56 and capsid protein is an important step in the virion assembly pathway. To our knowledge, this is the first study showing that enzymatic activity of a cellular helicase is critical for infectivity of flaviviruses.


title: A serological survey of selected pathogens in wild boar (Sus scrofa) in northern Turkey

text: During the hunting season in March 2012, a total of 93 blood samples were collected from wild boars (Sus scrofa) shot in the area of northern Turkey (Samsun and Gumushane provinces). These blood samples were examined by enzyme immunoassay (ELISA) for the presence of antibodies to classical swine fever virus (CSFV), Aujeszky’s disease virus (ADV), porcine reproductive and respiratory syndrome virus (PRRSV), porcine respiratory coronavirus (PRCV), swine influenza virus (SIV), porcine parvovirus (PPV), swine vesicular disease virus (SVDV), hepatitis E virus (HEV), African swine fever virus (ASFV), porcine rotavirus (PRV), transmissible gastroenteritis virus (TGEV) and bovine viral diarrhoea virus (BVDV). Out of 93 serum samples examined, 65 (69.9 %) were positive for PRV, 22 (23.7 %) were positive for ADV, 5 (5.4 %) were positive for BVDV, 4 (4.3 %) were positive for PPV and 2 (2.2 %) were positive for PRRSV. All sera were negative for ASFV, SVDV, HEV, SIV, PRCV, TGEV and CSFV. The results, recorded for the first time in Turkey, supported the hypothesis that wild boar act as a potential reservoir of selected viruses and thus have a role in the epidemiology of these diseases.


title: AUTOPSIAS EN CASOS SOSPECHOSOS DE SARS-CoV-2

text: Resumen La medicina forense debe contemplar la posibilidad de que fallecidos por causas violentas o desconocidas puedan estar infectados por el virus SARS-CoV-2, o que el diagnóstico de la enfermedad tenga implicaciones legales, lo que exige un conocimiento adecuado de la epidemiología de la enfermedad, de las medidas de protección, de la toma de muestras y de las características anatomopatológicas. La práctica de autopsias en fallecidos por COVID-19 se ha visto limitada por las obligadas medidas preventivas frente al contagio y por la necesidad de disponer de instalaciones con nivel de protección frente a riesgos biológicos de nivel 3, de modo que las series publicadas hasta la fecha son escasas, y parciales, con abordajes limitados (autopsia mínimamente invasiva o biopsia con aguja gruesa). En este artículo se hace una revisión de los aspectos de la fisiopatología de la enfermedad que tienen repercusión en la infectividad de los tejidos y fluidos del cadáver, de las medidas de prevención del riesgo biológico, de la toma de muestras y de los hallazgos patológicos, tanto macroscópicos como microscópicos, asociados a la muerte provocada por la infección por el virus SARS-CoV-2. Abstract Forensic physicians should consider the possibility that people who have died from violent or unknown causes may be infected by the virus SARS-CoV-2, or that the diagnosis of the disease has legal implications, which requires adequate knowledge of the epidemiology of the disease, protective measures, adequate sampling and the pathological characteristics. The practice of autopsies on people who have died from COVID-19 has been limited by the mandatory preventive measures against contagion and by the need for facilities with a level of protection against level-3 biological risk, and therefore series published to date are scarce and partial,with limited approaches (minimally invasive autopsy or needle biopsy). This article reviews the aspects of the pathophysiology of the disease that have an impact on the infectivity of the body's tissues and fluids, measures for preventing biological risk, taking samples and pathological findings, both macroscopic and microscopic, associated with death caused by infection with the SARS-CoV-2 virus.


Sites for health rights: Local, national, regional and global


Los antimaláricos (cloroquina e hidroxicloroquina) en la pandemia Covid19


title: COVID‐19 in solid organ transplant recipients: Initial report from the US epicenter

text: Solid organ transplant recipients may be at a high risk for SARS‐CoV‐2 infection and poor associated outcomes. We herein report our initial experience with solid organ transplant recipients with SARS‐CoV‐2 infection at two centers during the first 3 weeks of the outbreak in New York City. Baseline characteristics, clinical presentation, antiviral and immunosuppressive management were compared between patients with mild/moderate and severe disease (defined as ICU admission, intubation or death). Ninety patients were analyzed with a median age of 57 years. Forty‐six were kidney recipients, 17 lung, 13 liver, 9 heart, and 5 dual‐organ transplants. The most common presenting symptoms were fever (70%), cough (59%), and dyspnea (43%). Twenty‐two (24%) had mild, 41 (46%) moderate, and 27 (30%) severe disease. Among the 68 hospitalized patients, 12% required non‐rebreather and 35% required intubation. 91% received hydroxychloroquine, 66% azithromycin, 3% remdesivir, 21% tocilizumab, and 24% bolus steroids. Sixteen patients died (18% overall, 24% of hospitalized, 52% of ICU) and 37 (54%) were discharged. In this initial cohort, transplant recipients with COVID‐19 appear to have more severe outcomes, although testing limitations likely led to undercounting of mild/asymptomatic cases. As this outbreak unfolds, COVID‐19 has the potential to severely impact solid organ transplant recipients.


title: Inter-state transmission potential and vulnerability of COVID-19 in India

text: Abstract Since the first case of COVID-19 traced in India on 30th January 2020, the total no. of confirmed cases is amplified. To assess the inter-state diversity in spreading potentiality of COVID-19, the exposure, readiness and resilience capability have been studied. On the basis of the extracted data, the outbreak scenario, growth rate, testing amenities have been analysed. The study reflects that there is an enormous disparity in growth rate and total COVID-19 cases. The major outbreak clusters associated with major cities of India. COVID-19 cases are very swiftly amplifying with exponential growth in every four to seven days in main affected states during first phase of lockdown. The result shows the vibrant disproportion in the aspect of, hospital bed ratio, coronavirus case-hospital bed ratio, provision of isolation and ventilators, test ratio, distribution of testing laboratories and accessibility of test centres all over India. The study indicates the sharp inequality in transmission potentiality and resilience capacity of different states. Every state and union territory are not well-prepared to contain the spreading of Covid-19. The strict protective measures and uniform resilience system must be implemented in every corner of India to battle against the menace of Covid-19.


title: Coding-Complete Genome Sequences of Two SARS-CoV-2 Isolates from Early Manifestations of COVID-19 in Israel

text: We announce the genome sequences of two strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolated in Israel, one imported by a traveler who returned from Japan and the second strain collected from a patient infected by a traveler returning from Italy The sequences obtained are valuable as early manifestations for future follow-up of the local spread of the virus in Israel


title: World Health Organization declares global emergency: A review of the 2019 novel coronavirus (COVID-19)

text: Abstract An unprecedented outbreak of pneumonia of unknown aetiology in Wuhan City, Hubei province in China emerged in December 2019. A novel coronavirus was identified as the causative agent and was subsequently termed COVID-19 by the World Health Organization (WHO). Considered a relative of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), COVID-19 is caused by a betacoronavirus named SARS-CoV-2 that affects the lower respiratory tract and manifests as pneumonia in humans. Despite rigorous global containment and quarantine efforts, the incidence of COVID-19 continues to rise, with 90,870 laboratory-confirmed cases and over 3,000 deaths worldwide. In response to this global outbreak, we summarise the current state of knowledge surrounding COVID-19.


title: Rapid selection of a human monoclonal antibody that potently neutralizes SARS-CoV-2 in two animal models

text: Effective therapies are urgently needed for the SARS-CoV-2/COVID19 pandemic. We identified panels of fully human monoclonal antibodies (mAbs) from eight large phage-displayed Fab, scFv and VH libraries by panning against the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) glycoprotein. One high affinity mAb, IgG1 ab1, specifically neutralized replication competent SARS-CoV-2 with exceptional potency as measured by two different assays. There was no enhancement of pseudovirus infection in cells expressing Fcγ receptors at any concentration. It competed with human angiotensin-converting enzyme 2 (hACE2) for binding to RBD suggesting a competitive mechanism of virus neutralization. IgG1 ab1 potently neutralized mouse ACE2 adapted SARS-CoV-2 in wild type BALB/c mice and native virus in hACE2 expressing transgenic mice. The ab1 sequence has relatively low number of somatic mutations indicating that ab1-like antibodies could be quickly elicited during natural SARS-CoV-2 infection or by RBD-based vaccines. IgG1 ab1 does not have developability liabilities, and thus has potential for therapy and prophylaxis of SARS-CoV-2 infections. The rapid identification (within 6 days) of potent mAbs shows the value of large antibody libraries for response to public health threats from emerging microbes.


title: Chirurgie endocrinienne au cours et au décours de l’épidémie de COVID-19: Recommandations de l’AFCE

text: Résumé La pandémie de COVID-19 impose une réorganisation majeure de l’ensemble de notre système de soins. En France, des règles générales ont été diffusées au niveau national et sont déclinées par chaque établissement, public comme privé, sur l'ensemble du territoire. Ces recommandations, rédigées par un groupe d’experts sous l’égide de l’Association Francophone de Chirurgie Endocrinienne (AFCE), ont pour objectif de proposer des principes spécifiques de prise en charge chirurgicale au cours et au décours de l’épidémie de COVID- 19, pour les pathologies chirurgicales de la thyroïde, des parathyroïdes, du pancréas endocrine, et des surrénales. Abstract The Covid-19 pandemic commands a major reorganization of the entire French healthcare system. In France, general rules have been issued nationally and implemented by each healthcare center, both public and private, throughout France. Guidelines drafted by an expert group led by the French-speaking Association of Endocrine Surgery (AFCE) propose specific surgical management principles for thyroid, parathyroid, endocrine pancreas and adrenal surgery during and after the Covid-19 epidemic.


title: Process Characterization and Biophysical Analysis for a Yeast-Expressed Phlebotomus papatasi Salivary Protein (PpSP15) as a Leishmania Vaccine Candidate

text: Abstract Cutaneous leishmaniasis is a neglected tropical disease caused by the parasite Leishmania and transmitted by sandflies. It has become a major health problem in many tropical and subtropical countries, especially in regions of conflict and political instability. Currently, there are only limited drug treatments and no available licensed vaccine; thus, the need for more therapeutic interventions remains urgent. Previously, a DNA vaccine encoding a 15 kDa sandfly (Phlebotomus papatasi) salivary protein (PpSP15) and recombinant nonpathogenic Leishmania tarentolae secreting PpSP15 have been shown to induce protective immunity against Leishmania major in mice, demonstrating that PpSP15 is a promising vaccine candidate. In this study, we developed a fermentation process in yeast with a yield of ~1g PpSP15/L and a scalable purification process consisting of only 2 chromatographic purification steps with high binding capacity for PpSP15, suggesting that PpSP15 can be produced economically. The biophysical/biochemical analysis of the purified PpSP15 indicated that the protein was of high purity (>97%) and conformationally stable between pH 4.4 and 9.0. More importantly, the recombinant protein had a defined structure similar to that of the related PdSP15 from Phlebotomus duboscqi, implying the suitability of the yeast expression system for producing a correctly folded PpSP15.


title: Evaluation of hospital disaster preparedness by a multi-criteria decision making approach: The case of Turkish hospitals

text: Considering the unexpected emergence of natural and man-made disasters over the world and Turkey, the importance of preparedness of hospitals, which are the first reference points for people to get healthcare services, becomes clear. Determining the level of disaster preparedness of hospitals is an important and necessary issue. This is because identifying hospitals with low level of preparedness is crucial for disaster preparedness planning. In this study, a hybrid fuzzy decision making model was proposed to evaluate the disaster preparedness of hospitals. This model was developed using fuzzy analytic hierarchy process (FAHP)-fuzzy decision making trial and evaluation laboratory (FDEMATEL)-technique for order preference by similarity to ideal solutions (TOPSIS) techniques and aimed to determine a ranking for hospital disaster preparedness. FAHP is used to determine weights of six main criteria (including hospital buildings, equipment, communication, transportation, personnel, flexibility) and a total of thirty-six sub-criteria regarding disaster preparedness. At the same time, FDEMATEL is applied to uncover the interdependence between criteria and sub-criteria. Finally, TOPSIS is used to obtain ranking of hospitals. To provide inputs for TOPSIS implementation, some key performance indicators are established and related data is gathered by the aid of experts from the assessed hospitals. A case study considering 4 hospitals from the Turkish healthcare sector was used to demonstrate the proposed approach. The results evidenced that Personnel is the most important factor (global weight = 0.280) when evaluating the hospital preparedness while Flexibility has the greatest prominence (c + r = 23.09).


title: A multiplex PCR assay for the detection of five influenza viruses using a dual priming oligonucleotide system

text: BACKGROUND: A cost-effective, accurate and rapid simultaneous multiplex assay is required for testing and diagnoses of conventional and emerging viruses in clinical virology laboratories. We developed and optimized a dual priming oligonucleotide (DPO) multiplex PCR assay for detecting influenza viruses including seasonal H1N1, 2009 pandemic H1N1, H3N2, influenza B and H5N1. METHODS: The optimized multiplex DPO PCR was used to detect 233 clinical human samples. The results were compared to those obtained with RT-qPCR, conventional PCR and immunochromatographic assay. RESULTS: Specificity analysis revealed that the DPO PCR assay amplified each target virus without any cross-amplification. Statistical analysis demonstrated that the multiplex DPO-PCR sensitivity was higher than for the immunochromatographic assay and lower than for qPCR, while no significant difference was observed compared with conventional PCR, when detecting influenza A and B. Additional experiments using the same sample panel indicated no significant differences between the number of positive samples detected by multiplex DPO PCR and RT-qPCR when applying a Cq with a value lower than 30. CONCLUSIONS: The five-targeted simultaneous multiplex DPO PCR assay could be easily adopted into routine practice. This approach is cost effective with a short running time, low technical requirements for the detection of influenza virus and early diagnosis in clinical laboratories.


Anaplasma phagocytophilum Infection in North Norway. The First Laboratory Confirmed Case


Traditional and complementary treatments do have a role to play in global health, but probably not in emerging pandemics


title: Social Equity and COVID‐19: The Case of African Americans

text: Emerging statistics demonstrate that COVID‐19 disproportionately affects African Americans. The effects of COVID‐19 for this population are inextricably linked to areas of systemic oppression and disenfranchisement, which are further exacerbated by COVID‐19: (1) healthcare inequality; (2) segregation, overall health, and food insecurity; (3) underrepresentation in government and the medical profession; and (4) inequalities in participatory democracy and public engagement. Following a discussion of these issues, this article shares early and preliminary lessons and strategies on how public administration scholars and practitioners can lead in crafting equitable responses to this global pandemic to uplift the African American community. This article is protected by copyright. All rights reserved.


title: Fowl adenovirus recombinant expressing VP2 of infectious bursal disease virus induces protective immunity against bursal disease

text: The right hand end Nde I fragment 3 (90.8–100 map units) of the fowl adenovirus serotype 10 (FAV-10) was characterised so as to allow the location of an insertion site for recombinant vector construction. Infectious bursal disease virus (IBDV) VP2 gene from the Australian classical strain 002/73, under the control of the FAV-10 major late promoter/leader sequence (MLP/LS) was inserted into a unique Not I site that was generated at 99.5 map units. This recombinant virus was produced without deletion of any portion of the FAV-10 genome. When administered to specific pathogen free (SPF) chickens intravenously, intraperitoneally, subcutaneously or intramuscularly, it was shown that the FAV-10/VP2 recombinant induced a serum VP2 antibody response and protected chickens against challenge with IBDV V877, an intermediate virulent classical strain. Birds were not protected when the recombinant was delivered via the conjunctival sac.


title: COVID-19 in a MS patient treated with ocrelizumab: does immunosuppression have a protective role?

text: Abstract Background Coronavirus disease 19 (COVID-19) is a novel disease entity that is spreading throughout the world. It has been speculated that patients with comorbidities and elderly patients could be at high risk for respiratory insufficiency and death. Immunosuppression could expose infected patients to even higher risks of disease complications due to dampened immune response. However, it has been speculated that overactive immune response could drive clinical deterioration and, based on this hypothesis, several immunosuppressants are currently being tested as potential treatment for COVID-19. Methods In this paper we report on a patient that has been treated with ocrelizumab (a B-cell depleting monoclonal antibody) for primary progressive multiple sclerosis who developed COVID-19. Results Despite complete B cell depletion, patient symptoms abated few days after hospitalization, and he was discharged to home-quarantine. Phone interview follow-up confirmed that, after 14 days, no new symptoms occurred. Discussion This report supports the putative role of immunosuppressive therapy in COVID-19 affected patients.


Rapid health systems change: online medical consultations to fight COVID-19


title: Establishment of Fruit Bat Cells (Rousettus aegyptiacus) as a Model System for the Investigation of Filoviral Infection

text: BACKGROUND: The fruit bat species Rousettus aegyptiacus was identified as a potential reservoir for the highly pathogenic filovirus Marburg virus. To establish a basis for a molecular understanding of the biology of filoviruses in the reservoir host, we have adapted a set of molecular tools for investigation of filovirus replication in a recently developed cell line, R06E, derived from the species Rousettus aegyptiacus. METHODOLOGY/PRINCIPAL FINDINGS: Upon infection with Ebola or Marburg viruses, R06E cells produced viral titers comparable to VeroE6 cells, as shown by TCID(50) analysis. Electron microscopic analysis of infected cells revealed morphological signs of filovirus infection as described for human- and monkey-derived cell lines. Using R06E cells, we detected an unusually high amount of intracellular viral proteins, which correlated with the accumulation of high numbers of filoviral nucleocapsids in the cytoplasm. We established protocols to produce Marburg infectious virus-like particles from R06E cells, which were then used to infect naïve target cells to investigate primary transcription. This was not possible with other cell lines previously tested. Moreover, we established protocols to reliably rescue recombinant Marburg viruses from R06E cells. CONCLUSION/SIGNIFICANCE: These data indicated that R06E cells are highly suitable to investigate the biology of filoviruses in cells derived from their presumed reservoir.


title: Type 3 hypersensitivity in COVID-19 vasculitis

text: Coronavirus Disease 2019 (COVID-19) is an ongoing public health emergency and new knowledge about its immunopathogenic mechanisms is deemed necessary in the attempt to reduce the death burden around the world. For the first time in worldwide literature, we provide scientific evidence that in COVID-19 vasculitis a life-threatening escalation from type 2 T-helper immune response (humoral immunity) to type 3 hypersensitivity (immune complex disease) takes place. The subsequent deposition of immune complexes inside the vascular walls is supposed to induce a severe inflammatory state and a cytokine release syndrome, whose interleukin-6 is the key myokine, from the smooth muscle cells of blood vessels.


title: Respiratory viral infection in the chronic persistent phase of chronic rhinosinusitis

text: OBJECTIVES/HYPOTHESIS: The role of respiratory viral infection in the pathogenesis of chronic rhinosinusitis (CRS) has been rarely studied and remains controversial. The aim of this study was to explore the prevalence of respiratory viruses in the chronic status of CRS. STUDY DESIGN: A case‐control prospective study. METHODS: Fifty‐three control subjects, and 67 CRS with nasal polyp (CRSwNP) and 61 CRS without nasal polyp (CRSsNP) patients without signs of acute viral infection were enrolled. Epithelial cells scraped from the middle nasal meatus were tested for the nucleic acid of nine common respiratory viruses using polymerase chain reaction assay. The clinical disease severity was compared between subjects with and without viral infection. RESULTS: The overall detection rate of viral infection was 75.47%, 68.66%, and 73.77% in controls, CRSwNP, and CRSsNP, respectively, and no significant difference among studied groups was observed. There was no significant difference in detection rate of any specific individual virus or multiple viruses among the groups studied either. Visual analog scale scores of symptoms, computed tomography scores, or endoscope scores did not show obvious difference between subjects with and without viral infection. CONCLUSIONS: Although a high frequency of viral infection could be observed in the middle nasal meatus, no increase of frequency of viral infection could be demonstrated in chronic persistent phase of CRSsNP and CRSwNP. The contribution of the interaction between viral infection and host immunity to the pathogenesis of CRS remains to be determined. LEVEL OF EVIDENCE: 3b. Laryngoscope, 124:832–837, 2014


title: Unexplained Deaths and Critical Illnesses of Suspected Infectious Cause, Taiwan, 2000–2005

text: We report 5 years’ surveillance data from the Taiwan Centers for Disease Control on unexplained deaths and critical illnesses suspected of being caused by infection. A total of 130 cases were reported; the incidence rate was 0.12 per 100,000 person-years; and infectious causes were identified for 81 cases (62%).


title: When two pandemics meet: Why is obesity associated with increased COVID-19 mortality?

text: Abstract A growing body of evidence indicates that obesity is strongly and independently associated with adverse outcomes of COVID-19 including death. By combining emerging knowledge of the pathological processes involved in COVID-19 with insights into the mechanisms underlying the adverse health consequences of obesity, we present some hypotheses regarding the deleterious impact of obesity on the course of COVID-19. These hypotheses are testable and could guide therapeutic and preventive interventions. As obesity is now almost ubiquitous and no vaccine for COVID-19 is currently available, even a modest reduction in the impact of obesity on mortality and morbidity from this viral infection could have profound consequences for public health.


title: The challenges of COVID-19 in nursing education: The time for faculty leadership training is now

text: • Nursing faculty have an influential and critical role in both classroom, clinical, and university setting. • Faculty must engage in leadership training to be able to master the ever-evolving complex challenges of the faculty role. • Leadership training is critical for faculty, student, and university success.


title: Measuring Social Contacts in the Emergency Department

text: BACKGROUND: Infectious individuals in an emergency department (ED) bring substantial risks of cross infection. Data about the complex social and spatial structure of interpersonal contacts in the ED will aid construction of biologically plausible transmission risk models that can guide cross infection control. METHODS AND FINDINGS: We sought to determine the number and duration of contacts among patients and staff in a large, busy ED. This prospective study was conducted between 1 July 2009 and 30 June 2010. Two 12-hour shifts per week were randomly selected for study. The study was conducted in the ED of an urban hospital. There were 81 shifts in the planned random sample of 104 (78%) with usable contact data, during which there were 9183 patient encounters. Of these, 6062 (66%) were approached to participate, of which 4732 (78%) agreed. Over the course of the year, 88 staff members participated (84%). A radiofrequency identification (RFID) system was installed and the ED divided into 89 distinct zones structured so copresence of two individuals in any zone implied a very high probability of contact <1 meter apart in space. During study observation periods, patients and staff were given RFID tags to wear. Contact events were recorded. These were further broken down with respect to the nature of the contacts, i.e., patient with patient, patient with staff, and staff with staff. 293,171 contact events were recorded, with a median of 22 contact events and 9 contacts with distinct individuals per participant per shift. Staff-staff interactions were more numerous and longer than patient-patient or patient-staff interactions. CONCLUSIONS: We used RFID to quantify contacts between patients and staff in a busy ED. These results are useful for studies of the spread of infections. By understanding contact patterns most important in potential transmission, more effective prevention strategies may be implemented.


title: Mannose‐binding lectin cord blood levels and respiratory symptoms during infancy: a prospective birth cohort study

text: Respiratory infections cause considerable morbidity during infancy. The impact of innate immunity mechanisms, such as mannose‐binding lectin (MBL), on respiratory symptoms remains unclear. The aims of this study were to investigate whether cord blood MBL levels are associated with respiratory symptoms during infancy and to determine the relative contribution of MBL when compared with known risk factors. This is a prospective birth cohort study including 185 healthy term infants. MBL was measured in cord blood and categorized into tertiles. Frequency and severity of respiratory symptoms were assessed weekly until age one. Association with MBL levels was analysed using multivariable random effects Poisson regression. We observed a trend towards an increased incidence rate of severe respiratory symptoms in infants in the low MBL tertile when compared with infants in the middle MBL tertile [incidence rate ratio (IRR) = 1.59; 95% confidence interval (CI): 0.95–2.66; p = 0.076]. Surprisingly, infants in the high MBL tertile suffered significantly more from severe and total respiratory symptoms than infants in the middle MBL tertile (IRR = 1.97; 95% CI: 1.20–3.25; p = 0.008). This association was pronounced in infants of parents with asthma (IRR = 3.64; 95% CI: 1.47–9.02; p = 0.005). The relative risk associated with high MBL was similar to the risk associated with well‐known risk factors such as maternal smoking or childcare. In conclusion the association between low MBL levels and increased susceptibility to common respiratory infections during infancy was weaker than that previously reported. Instead, high cord blood MBL levels may represent a so far unrecognized risk factor for respiratory morbidity in infants of asthmatic parents.


title: Rapid Screening for Entry Inhibitors of Highly Pathogenic Viruses under Low-Level Biocontainment

text: Emerging viruses including Nipah, Hendra, Lujo, and Junin viruses have enormous potential to spread rapidly. Nipah virus, after emerging as a zoonosis, has also evolved the capacity for human-to-human transmission. Most of the diseases caused by these pathogens are untreatable and require high biocontainment conditions. Universal methods for rapidly identifying and screening candidate antivirals are urgently needed. We have developed a modular antiviral platform strategy that relies on simple bioinformatic and genetic information about each pathogen. Central to this platform is the use of envelope glycoprotein cDNAs to establish multi-cycle replication systems under BSL2 conditions for viral pathogens that normally require BSL3 and BSL4 facilities. We generated monoclonal antibodies against Nipah G by cDNA immunization in rats, and we showed that these antibodies neutralize both Nipah and Hendra live viruses. We then used these effective Henipavirus inhibitors to validate our screening strategy. Our proposed strategy should contribute to the response capability for emerging infectious diseases, providing a way to initiate antiviral development immediately upon identifying novel viruses.