title: Comparison of Estimated Rates of Coronavirus Disease 2019 (COVID-19) in Border Counties in Iowa Without a Stay-at-Home Order and Border Counties in Illinois With a Stay-at-Home Order

text: IMPORTANCE: Iowa is 1 of 5 states in the US that have not issued a stay-at-home order during the coronavirus disease 2019 (COVID-19) pandemic. There is no empirical evidence on whether issuing a stay-at-home order in Iowa could have been associated with a reduced rate of COVID-19 infections in the state. OBJECTIVE: To compare COVID-19 cases in border counties in Iowa, which did not issue a stay-at-home order, with cases in border counties in Illinois, which did issue a stay-at-home order. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study with a difference-in-differences design compared daily changes in COVID-19 cases per 10 000 residents in 8 Iowa counties bordering Illinois with those in the 7 Illinois counties bordering Iowa before and after Illinois issued a stay-at-home order on March 21, 2020. Additional sensitivity analyses were conducted to account for differences in timing of closing schools and nonessential businesses between the 2 states and differential trends in COVID-19 cases by county population density and poverty rates. EXPOSURES: Issuing a stay-at-home order. MAIN OUTCOMES AND MEASURES: Comparison of cumulative cases of COVID-19 per 10 000 residents in border counties in Iowa and Illinois. RESULTS: The total populations were 462 445 in the Iowa border counties and 272 385 in the Illinois border counties. Population density was higher in the Iowa counties (114.2 people per square mile) than in the Illinois counties (78.2 people per square mile). Trends of cumulative COVID-19 cases per 10 000 residents for the Iowa and Illinois border counties were comparable before the Illinois stay-at-home order, which went into effect at 5:00 pm on March 21 (March 15 to March 21: 0.024 per 10 000 residents vs 0.026 per 10 000 residents). After that, cases increased more quickly in Iowa and more slowly in Illinois. Within 10, 20, and 30 days after the enactment of the stay-at-home order in Illinois, the difference in cases was −0.51 per 10 000 residents (SE, 0.09; 95% CI, −0.69 to −0.32; P < .001), −1.15 per 10 000 residents (SE, 0.49; 95% CI, −2.12 to −0.18; P = .02), and −4.71 per 10 000 residents (SE, 1.99; 95% CI, −8.64 to −0.78; P = .02), respectively. The estimates indicate excess cases in the border Iowa counties by as many as 217 cases after 1 month without a stay-at-home order. This estimate of excess cases represents 30.4% of the 716 total cases in those Iowa counties by that date. Sensitivity analyses addressing differences in timing of closing schools and nonessential businesses and differences in county population density and poverty rates between the 2 states supported these findings. CONCLUSIONS AND RELEVANCE: This cross-sectional study with a difference-in-differences design found an increase in estimated rates of COVID-19 cases per 10 000 residents in the border counties in Iowa compared with the border counties in Illinois following a stay-at-home order that was implemented in Illinois but not in Iowa.


title: Convalescent plasma therapy in patients with COVID‐19

text: There are currently no licensed vaccines or therapeutics for COVID‐19. Anti‐SARS CoV‐2 antibody‐containing plasmas, obtained from the recovered individuals who had confirmed COVID‐19, have been started to be collected using apheresis devices and stored in blood banks in some countries in order to administer to the patients with COVID‐19 for reducing the need of intensive care and the mortality rates. Therefore, in this review, we aim to point out some important issues related to convalescent plasma (CP) and its use in COVID‐19. CP may be an adjunctive treatment option to the anti‐viral therapy. The protective effect of CP may continue for weeks and months. After the assessment of the donor, 200‐600 mL plasma can be collected with apheresis devices. The donation interval may vary between countries. Even though limited published studies are not prospective or randomized, until the development of vaccines or therapeutics, CP seems to be a safe and probably effective treatment for critically ill patients with COVID‐19. It could also be used for prophylactic purposes but the safety and effectiveness of this approach should be tested in randomized prospective clinical trials.


title: Pentraxins and Collectins: Friend or Foe during Pathogen Invasion?

text: Innate immunity serves as the frontline defence against invading pathogens. Despite decades of research, new insights are constantly challenging our understanding of host-elicited immunity during microbial infections. Recently, two families of humoral innate immune proteins, pentraxins and collectins, have become a major focus of research in the field of innate immunity. Pentraxins and collectins are key players in activating the humoral arm of innate immunity, taking centre stage in immunoregulation and disease modulation. However, increasing evidence suggests that pentraxins and collectins can also mediate pathogenic effects during some infections. Herein, we discuss the protective and pathogenic effects of pentraxins and collectins, as well as their therapeutic significance.


title: Tsurumi ensures continued delivery capability

text: Tsurumi has confirmed that the majority of its product range continues to be available at short notice, despite the Covid-19 pandemic.


title: COVID-Toes or Pernio?

text: Abstract “COVID toes” are a new phenomenon of pernio-like lesions that has been associated with COVID-19 infection. As dermatology practices reopen and increase patient volumes amidst the waning of the coronavirus pandemic, it is important to consider the finding of pernio and pernio-like lesions in the context of both COVID-19 and its other possible etiologies. This article will discuss possible causes of pernio and pernio-like lesions and offer suggestions for appropriate diagnostic work-up and management when indicated.


title: A novel feline norovirus in diarrheic cats

text: Abstract By screening a collection of fecal samples from young cats housed in three different shelters in South Italy, noroviruses (NoVs) were found in 3/48 (6.2%) specimens of animals with enteritis signs while they were not detected in samples collected from healthy cats (0/57). Upon sequence analysis of the short RNA-dependent RNA polymerase (RdRp) region, the three strains displayed the highest nucleotide (nt) and amino acid (aa) identities to the prototype GIV.2 strain lion/Pistoia/387/06/ITA (91.0–93.0% nt and 97.0–98.0% aa). The sequence of ~3.4-kb portion at the 3′ end of the genome of a NoV strain, TE/77-13/ITA, was determined. In the full-length ORF2, encoding the VP1 capsid protein, the virus was genetically closest to the canine GVI.2 NoV strains C33/Viseu/2007/PRT and FD53/2007/ITA (81.0–84.0% nt and 93.0–94.0% aa identities), suggesting a recombination nature, with the cross-over site being mapped to the ORF1-ORF2 junction. Based on the full-length VP1 amino acid sequence, we classified the novel feline NoV, together with the canine strains Viseu and FD53, as a genotype 2, within the genogroup GVI. These findings indicate that, as observed for GIV NoV, GVI strains may infect both the canine and feline host. Unrestricted circulation of NoV strains in small carnivores may provide the basis for quick genetic diversification of these viruses by recombination. Interspecies circulation of NoVs in pets must also be considered when facing outbreaks of enteric diseases in these animals.


title: Optimal fecal assessment

text: Abstract Fecal testing is a common component of most gastrointestinal work-ups. A multitude of diagnostic techniques are available for identifying parasites and pathogens, or showing abnormalities of flora. Optimal fecal assessment involves careful formulation of a differential list based on signalment, history, and clinical signs. Tests should be selected and interpreted based on their relative sensitivity and specificity for specific conditions. It is essential to use effective testing methods for the etiologies of concern. This article reviews the plethora of diagnostic techniques available for fecal assessment. Indications, limitations, and issues of specimen handling for each technique are discussed. The optimal approach to the diagnosis of some common parasites, pathogens, abnormalities of flora, and metabolic conditions are covered.


title: Quantitative analysis of chest CT imaging findings with the risk of ARDS in COVID-19 patients: a preliminary study

text: Background: The coronavirus disease 2019 (COVID-19) has rapidly become a pandemic worldwide The value of chest computed tomography (CT) is debatable during the treatment of COVID-19 patients Compared with traditional chest X-ray radiography, quantitative CT may supply more information, but its value on COVID-19 patients was still not proven Methods: An automatic quantitative analysis model based on a deep network called VB-Net for infection region segmentation was developed A quantitative analysis was performed for patients diagnosed as severe COVID 19 The quantitative assessment included volume and density among the infectious area The primary clinical outcome was the existence of acute respiratory distress syndrome (ARDS) A univariable and multivariable logistic analysis was done to explore the relationship between the quantitative results and ARDS existence Results: The VB-Ne model was sensitive and stable for pulmonary lesion segmentation, and quantitative analysis indicated that the total volume and average density of the lung lesions were not related to ARDS However, lesions with specific density changes showed some influence on the risk of ARDS The proportion of lesion density from -549 to -450 Hounsfield unit (HU) was associated with increased risk of ARDS, while the density was ranging from -149 to -50 HU was related to a lowered risk of ARDS Conclusions: The automatic quantitative model based on VB-Ne can supply useful information for ARDS risk stratification in COVID-19 patients during treatment


title: Imiquimod - A toll like receptor 7 agonist - Is an IDEAL OPTION for MANAGEMENT of COVID 19

text: According to numerous recent publications, the COVID-19 patients have lymphopenia, higher infection-related biomarkers and several elevated inflammatory cytokines (i.e. tumor necrosis factor (TNF)-α, interleukin IL-2R and IL-6). The total number of B cells, T cells and NK cells are significantly decreased. RNA viruses, SARS-CoV-2 included, hit the innate immune system in order to cause infection, through TLRs 3, 7 and 8. Imiquimod is an immune-stimulator that activates TLR 7 and can be used to enhance the innate and adaptive immunity. Preclinical and clinical trials are proposed.


Coronavirus volunteers, bushfire deaths and a telescope delay


The impact of covid-19 on research


title: Delivery to the lower respiratory tract is required for effective immunization with Newcastle disease virus-vectored vaccines intended for humans

text: Newcastle disease virus (NDV), an avian virus, is being evaluated for the development of vectored human vaccines against emerging pathogens. Previous studies of NDV-vectored vaccines in a mouse model suggested their potency after delivery by injection or by the intranasal route. We compared the efficacy of various routes of delivery of NDV-vectored vaccines in a non-human primate model. While delivery of an NDV vectored vaccine by the combined intranasal/intratracheal route elicited protective immune responses, delivery by the subcutaneous route or the intranasal route alone elicited limited or no protective immune responses, suggesting the necessity for vaccine delivery to the lower respiratory tract. Furthermore, direct comparison of a vaccine based on an NDV mesogenic strain (NDV-BC) with a similarly designed NDV vector based on a modified lentogenic strain carrying a polybasic F cleavage site (NDV-VF) suggested that the two NDV strains were similar in immunogenicity and were equally protective.


title: Diagnosis and treatment of novel coronavirus pneumonia based on the theory of traditional Chinese medicine

text: Abstract Since the outbreak of novel coronavirus pneumonia (coronavirus disease 2019, COVID-19) in December 2019, it has rapidly spread to 187 countries, causing serious harm to the health of people and a huge social burden. However, currently, drugs specifically approved for clinical use are not available, except for vaccines against COVID-19 that are being evaluated. Traditional Chinese medicine (TCM) is capable of performing syndrome differentiation and treatment according to the clinical manifestations of patients, and has a better ability of epidemic prevention and control. The authors comprehensively analyzed the etiology and pathogenesis of COVID-19 based on the theory of TCM, and discussed its syndrome differentiation, treatment and prevention measures so as to provide strategies and reference for the prevention and treatment with TCM.


title: Epizootic diarrhoea of adult cattle associated with a coronavirus-like agent

text: Abstract An epizootic of acute diarrhoea of adult cattle occured in Japan during the winter of 1976 to 1977. A majority of adult cattle clinically diagnosed as having the disease, showed a significant rises in antibody titres to bovine coronavirus, whereas only a smal; minority showed serological evidence of recent infection with calf rotavirus, bovine adenovirus type 7, parainfluenza virus type 3, or bovine viral diarrhoea-mucosal disease virus. A coronavirus-like agent was detected by electron-microscopy in faecal material from a cow with diarrhoea, and was subsequently isolated in primary bovine kidney cell cultures.


Prevalence and phylogenetic characterization of canine coronavirus from diseased pet dogs in Beijing, China


title: The Past, Present, and Future of Orthopaedic Education: Lessons Learned from the COVID-19 Pandemic

text: Abstract The COVID-19 global pandemic has upended nearly every medical discipline, dramatically impacted patient care, and has had far-reaching effects on surgeon education. In many areas of the country, elective orthopaedic surgery has completely stopped to ensure that resources are available for the critically ill and to minimize the spread of disease. COVID-19 is forcing many around the world to reevaluate existing processes and organizations and adapt to carry out business, of which medicine and education are not immune. The majority of national and international orthopaedic conferences, training programs, and workshops have been postponed or canceled, and we are now critically evaluating the delivery of education to our colleagues as well as residents and fellows. This manuscript describes the evolution of orthopaedic education and significant paradigm shifts necessary to continue to teach ourselves and the future leaders of our noble profession.


SARS-CoV2 en pediatría: más allá de la infección


title: The effects of disease severity, use of corticosteroids and social factors on neuropsychiatric complaints in severe acute respiratory syndrome (SARS) patients at acute and convalescent phases

text: Abstract Objective. – To evaluate the effects of disease severity, corticosteroids and social factors on neuropsychiatric complaints in severe acute respiratory syndrome (SARS) patients, both during acute and convalescent phases. Subjects and methods. – Self-administered mail questionnaires survey to 308 SARS patients after discharging from hospital. Both patients and their families were asked about symptoms related to various neuropsychiatric domains, and the questions covered both acute and convalescent phases. Results. – Among the 102 (33%) valid replies, 65% had strong symptoms in convalescent phase as indicated by GHQ28 score ≥ 5. In multiple linear regression analysis, use of pulse steroid and total dosages of pulse steroid during hospitalisation were predictive for anxiety-depression, psychosis and behavioural symptoms in acute phase, the effects persisted in convalescent phase. Disease severity had direct correlation with symptoms in all neuropsychiatric domains at acute phase and anxiety-depression and cognition at convalescent phase. Health care workers had more neuropsychiatric complaints in both phases. Severity of symptoms, corticosteroids and social factors explained about half of the variances (R 2 = 52) in anxiety-depression at acute phase and 33% at convalescent phase. Conclusion. – Severe disease, high dose corticosteroids and being health care workers were independent predictors of neuropsychiatric complaints in both acute and convalescent phases.


title: Does moral reasoning influence public values for health care priority setting?: A population-based randomized stated preference survey

text: OBJECTIVE: Preferences of members of the public are recognized as important inputs into health care priority-setting, though knowledge of such preferences is scant. We sought to generate evidence of public preferences related to healthcare resource allocation among adults and children. METHODS: We conducted an experimental stated preference survey in a national sample of Canadian adults. Preferences were elicited across a range of scenarios and scored on a visual analogue scale. Intervention group participants were randomized to a moral reasoning exercise prior to each choice task. The main outcomes were the differences in mean preference scores by group, scenario, and demographics. RESULTS: Our results demonstrate a consistent preference by participants to allocate scarce health system resources to children. Exposure to the moral reasoning exercise weakened but did not eliminate this preference. Younger respondent age and parenthood were associated with greater preference for children. The top principles guiding participants’ allocative decisions were treat equally, relieve suffering, and rescue those at risk of dying. CONCLUSIONS: Our study affirms the relevance of age in public preferences for the allocation of scarce health care resources, demonstrating a significant preference by participants to allocate healthcare resources to children. However, this preference diminishes when challenged by exposure to a range of moral principles, revealing a strong public endorsement of equality of access. Definitions of value in healthcare based on clinical benefit and cost-effectiveness may exclude moral considerations that the public values, such as equality and humanitarianism, highlighting opportunities to enrich healthcare priority-setting through public engagement.


title: Niños con cáncer e infección viral respiratoria: epidemiología, diagnóstico y posibles tratamientos

text: Community-adquired respiratory viral infection is the most common cause of febrile infection in children, and an important cause of infection to consider in children with cancer. Nevertheless, there are few well-designed, controlled studies in this population, which makes it difficult to understand the importance, behaviour and management of these viruses in immunocompromised children. New diagnostic techniques in PCR-based microbiology, could provide many opportunities for early diagnosis, preventing the spread of the virus and to implement the correct therapy. It is important to design appropriate prospective studies to assess these types of infections in children with cancer. In this review we analyse the main studies published in the literature, evaluating the epidemiology, diagnosis and management of children with cancer and respiratory viral infection.


title: Shiga Toxin–Producing Escherichia coli (STEC)

text: Shiga toxin–producing Escherichia coli (STEC) are important enteric pathogens worldwide, causing diarrhea with or without blood visibly present and hemolytic uremic syndrome. STEC are unique among diarrheogenic E coli in producing Shiga toxin type 1 and type 2, the virulence factors responsible for bloody diarrhea and hemolytic uremic syndrome. Cattle and other ruminants are the natural reservoir of STEC as their normal intestinal flora. Humans become infected by consumption of foods contaminated with cattle feces. Early diagnosis of STEC infection is important because of the contraindication for treating STEC using antimicrobial agents, and the intense supportive care needed if renal failure occurs.


title: Evaluation and Management of Seasonal Influenza in the Emergency Department

text: Seasonal influenza causes significant morbidity and mortality, primarily due to increased complication rates among the elderly population and patients with chronic diseases. Timely diagnosis of influenza and early recognition of an influenza outbreak or epidemic are key components in preventing influenza-related complications, hospitalizations, and deaths. Emergency departments are the most frequent points of entry for most influenza cases and are well positioned to identify and manage influenza community outbreaks and epidemics. Emergency departments need specific infection control measures to curb the spread of influenza in the Emergency Department and hospital during the influenza season.


title: THREE INSIGHTS ON PSYCHONEUROIMMUNOLOGY OF MOOD DISORDERS TO BE TAKEN FROM THE COVID-19 PANDEMIC

text: Abstract In the recent months, the world was taken by surprise by the outbreak of a coronavirus (SARS-CoV-2) pandemic (COVID-19). The COVID-19 pandemic is a unique opportunity to advance the understanding of the association of respiratory viruses with mood disorders and suicide. In this editorial, we explore three insights to the neuropsychoneuroimmunology of mood disorders that could be taken from the COVID-19 pandemic.


title: Influence of COVID-19 on Cerebrovascular Disease and its Possible Mechanism

text: The global spread of COVID-19 has caused a substantial societal burden and become a major global public health issue. The COVID-19 elderly population with hypertension, diabetes, cardiovascular, and cerebrovascular diseases are at risk. Mortality rates are highest in these individuals if infected with COVID-19. Although the lungs are the main organs involved in acute respiratory distress syndrome caused by COVID-19 infection, COVID-19 triggers inflammatory and immune mechanisms, inducing a “cytokine storm” that aggravates disease progression and may lead to death. Presently, effective drugs are lacking, although current studies have confirmed that drugs with therapeutic potential include redaciclovir, lopinavir/ritonavir combined with interferon-β, convalescent plasma, and monoclonal antibodies. Currently, the most reasonable and effective way to prevent COVID-19 is to control the source of infection, terminate routes of transmission, and protect susceptible populations. With the rise of COVID-19 in China and worldwide, further prevention, diagnosis, and treatment measures are a critical unmet need. Cerebrovascular disease has high incidence, disability rate, and fatality rate. COVID-19 patient outcomes may also be complicated with acute stroke. This paper summarizes the influence of COVID-19 on cerebrovascular disease and discusses possible pathophysiological mechanisms to provide new angles for the prevention and diagnosis of this disease.


title: The microbiology of asthma

text: Asthma remains an important human disease that is responsible for substantial worldwide morbidity and mortality. The causes of asthma are multifactorial and include a complex mix of environmental, immunological and host genetic factors. In addition, epidemiological studies show strong associations between asthma and infection with respiratory pathogens, including common respiratory viruses such as rhinoviruses, human respiratory syncytial virus, adenoviruses, coronaviruses and influenza viruses, as well as bacteria (including atypical bacteria) and fungi. In this Review, we describe the many roles of microorganisms in the risk of developing asthma and in the pathogenesis of and protection against the disease, and we discuss the mechanisms by which infections affect the severity and prevalence of asthma.


title: Automated deep transfer learning-based approach for detection of COVID-19 infection in chest X-rays

text: The most widely used novel coronavirus (COVID-19) detection technique is a real-time polymerase chain reaction (RT-PCR). However, RT-PCR kits are costly and take 6-9 hours to confirm infection in the patient. Due to less sensitivity of RT-PCR, it provides high false-negative results. To resolve this problem, radiological imaging techniques such as chest X-rays and computed tomography (CT) are used to detect and diagnose COVID-19. In this paper, chest X-rays is preferred over CT scan. The reason behind this is that X-rays machines are available in most of the hospitals. X-rays machines are cheaper than the CT scan machine. Besides this, X-rays has low ionizing radiations than CT scan. COVID-19 reveals some radiological signatures that can be easily detected through chest X-rays. For this, radiologists are required to analyze these signatures. However, it is a time-consuming and error-prone task. Hence, there is a need to automate the analysis of chest X-rays. The automatic analysis of chest X-rays can be done through deep learning-based approaches, which may accelerate the analysis time. These approaches can train the weights of networks on large datasets as well as fine-tuning the weights of pre-trained networks on small datasets. However, these approaches applied to chest X-rays are very limited. Hence, the main objective of this paper is to develop an automated deep transfer learning-based approach for detection of COVID-19 infection in chest X-rays by using the extreme version of the Inception (Xception) model. Extensive comparative analyses show that the proposed model performs significantly better as compared to the existing models.


title: La BPCO : une maladie qui commence précocement

text: Résumé Cette revue générale aborde les mécanismes qui sous-tendent les phénomènes génétiques dans la BPCO. L’inflammation de la paroi bronchique met en jeu de nombreux mécanismes cellulaires et biochimiques. Les différents modèles expérimentaux de la maladie sont présentés en insistant sur l’importance du stress oxydatif, et sur les connaissances nouvelles concernant le microbiome pulmonaire. À partir de cette base physiopathologique, nous développons une réflexion sur les différentes cibles génétiques susceptibles d’influencer le modèle. Ces dernières sont à l’origine de recherches sur les marqueurs dans l’air exhalé et de nouveaux impacts pharmacologiques. Summary This general review deals with the mechanisms which underlie the genetic factors in COPD. Many cellular and biochemical mechanisms occur in bronchial inflammation. We present the experimental models of COPD, insisting on the importance of oxydative stress, and on recent knowledge about the lung microbiome. Starting from this pathophysiology basis, we show how various genetic targets are able to interfere with the disease model. Thanks to these genetic targets, new markers in exhaled breath condensates and new drug targets are rising.


title: Emerging virus diseases: can we ever expect the unexpected?

text: Emerging virus diseases are a major threat to human and veterinary public health. With new examples occurring approximately one each year, the majority are viruses originating from an animal host. Of the many factors responsible, changes to local ecosystems that perturb the balance between pathogen and principal host species is one of the major drivers, together with increasing urbanization of mankind and changes in human behavior. Many emerging viruses have RNA genomes and as such are capable of rapid mutation and selection of new variants in the face of environmental changes in host numbers and available target species. This review summarizes recent work on aspects of virus emergence and the current understanding of the molecular and immunological basis whereby viruses may cross between species and become established in new ecological niches. Emergence is hard to predict, although mathematical modeling and spatial epidemiology have done much to improve the prediction of where emergence may occur. However, much needs to be done to ensure adequate surveillance is maintained of animal species known to present the greatest risk thus increasing general alertness among physicians, veterinarians and those responsible for formulating public health policy.


title: The impact of coronavirus infectious disease 19 (COVID‐19) on oral health

text: Health services across the world face an unprecedented situation as a result of a global COVID‐19 outbreak. Urgent joined research efforts regarding the SARS‐COV‐2 rapid tests, accurate diagnosis, especially early recognition, and effective treatment of life‐threatening complications would be highly desirable for humanity and medical workforce all over the world that try to combat a current global pandemic threat. Due to indirect complex effect, intensified COVID‐19 therapies and multi‐drug treatment, it is believed that some oral conditions could be aggravated by COVID‐19 disease, particularly those with autoimmune aetiology, linked to compromised immune system or long‐term pharmacotherapy.


title: Proteintemplat‐gesteuerte Fragmentligationen – von der molekularen Erkennung zur Wirkstofffindung

text: Proteintemplat‐gesteuerte Fragmentligationen sind ein neuartiges Konzept zur Unterstützung der Wirkstofffindung und können dazu beitragen, die Wirksamkeit von Proteinliganden zu verbessern. Es handelt sich dabei um chemische Reaktionen zwischen niedermolekularen Verbindungen (“Fragmenten”), die die Oberfläche eines Proteins als Reaktionsgefäß verwenden, um die Bildung eines Proteinliganden mit erhöhter Bindungsaffinität zu katalysieren. Die Methode nutzt die molekulare Erkennung kleiner reaktiver Fragmente durch die Proteine sowohl zur Assemblierung der Liganden als auch zur Identifizierung bioaktiver Fragmentkombinationen. Chemische Synthese und Bioassay werden dabei in einem Schritt vereint. Dieser Aufsatz diskutiert die biophysikalischen Grundlagen der reversiblen und irreversiblen Fragmentligationen und gibt einen Überblick über die Methoden, mit denen die durch das Proteintemplat gebildeten Ligationsprodukte detektiert werden können. Der chemische Reaktionsraum und aktuelle Anwendungen wie auch die Bedeutung dieses Konzeptes für die Wirkstofffindung werden erörtert.


title: Protection of pigs by vaccination of pregnant sows against eastern equine encephalomyelitis virus

text: Abstract Serum-virus neutralizing antibodies were detected in serum and colostrum of sows vaccinated during pregnancy with commercially available vaccines against eastern equine encephalomyelitis virus (EEEV), and antibodies were detected in serum from nearly all pigs from vaccinated sows flllowing colostrum uptake. Serum-virus neutralizing antibody (SVN) test titers were measured in colostrum and pigs at the next farrowing, and additional vaccination of sows prior to the third farrowing led to elevated SVN titers in serum, colostrum and all pigs. Six pigs from vaccinated sows challenged at 8 to 9 days of age with 1 × 106 TCID50 EEEV did not develop the high temperatures or signs of central nervous system disease that 6 pigs from non-vaccinated sows developed. Virus was isolated from blood and oropharyngeal swabs from all pigs from non-vaccinated sows with blood virus titers as high as 9.3 × 104 TCID50, while only low levels of virus were detected in blood and oropharyngeal swabs from pigs from vaccinated sows. Virus was also isolated from tonsils collected at necropsy from 3 pigs from non-vaccinated and 1 pig from vaccinated sows. Vaccination of pregnant sows leads to development of maternal antibodies that are transmitted via colostrum to pigs and are protective against clinical EEEV related disease after experimental challenge with EEEV. In addition, vaccination prevents amplification of virus in infected pigs and could result in protection of animals and farm labor in the environment of infected pigs.


title: Ozone Is Associated With an Increased Risk of Respiratory Exacerbations in Patients With Cystic Fibrosis

text: Background Tropospheric oxidant pollutants may injure the respiratory tract. Cystic fibrosis (CF) respiratory disease involves significant inflammation and excessive oxidative stress, and exposure to air pollutants can magnify the lung damage. The objective of this study was to investigate the association between the short-term variation in the concentration of air pollutants in metropolitan São Paulo, Brazil, and the occurrence of respiratory exacerbations in children and adolescents with CF. Methods A longitudinal panel of repeated measurements was obtained from 103 patients attending the outpatient center of our institution from September 6, 2006 through September 4, 2007. Daily concentrations of inhaled particulate matter, sulfur dioxide, nitrogen dioxide, ozone (O3), carbon monoxide, and meteorologic variables, such as the minimum temperature and relative humidity, were evaluated. The generalized estimation equation model for binomial distribution was used to assess the impact of these measurements on the occurrence of acute respiratory exacerbations. Results In total, 103 patients with CF (median age, 8.9 years) made 408 visits, with a mean ± SD of 4 ± 1.74 visits per patient (range, 2-9). A respiratory disease exacerbation was diagnosed on 142 visits (38.4%). An interquartile range increase in the O3 concentration (45.62 μg/m3) had a positive, delayed (2 days after exposure) effect on the risk of a respiratory exacerbation (relative risk = 1.86; 95% CI, 1.14-3.02). Conclusions This study demonstrates that exposure to short-term air pollution in a large urban center increases the risk of a pulmonary exacerbation in patients with CF.


title: SURVEY AND SUMMARY: Roles of 5-substituents of tRNA wobble uridines in the recognition of purine-ending codons

text: Many tRNA molecules that recognize the purine-ending codons but not the pyrimidine-ending codons have a modified uridine at the wobble position, in which a methylene carbon is attached directly to position 5 of the uracil ring. Although several models have been proposed concerning the mechanism by which the 5-substituents regulate codon-reading properties of the tRNAs, none could explain recent results of the experiments utilizing well-characterized modification-deficient strains of Escherichia coli. Here, we first summarize previous studies on the codon-reading properties of tRNA molecules with a U derivative at the wobble position. Then, we propose a hypothetical mechanism of the reading of the G-ending codons by such tRNA molecules that could explain the experimental results. The hypothesis supposes unconventional base pairs between a protonated form of the modified uridines and the G at the third position of the codon stabilized by two direct hydrogen bonds between the bases. The hypothesis also addresses differences between the prokaryotic and eukaryotic decoding systems.


Infection control challenge in setting up a temporary test centre at the international airport for rapid diagnosis of coronavirus disease 2019 (COVID-19) due to SARS-CoV-2


title: Protein microarray using α-amino acids as metal tags on chips

text: Abstract Procedures for synthesizing α-amino acids on a chip for coordination with transitional metal ions and a His-Tagged protein have been successfully developed as a stable protein microarray. Using the recombinant His-Tagged 3CL-protease (3CLpro) as a model for attachment to chips containing d-/l-Glu, Asp, Orn, Ser via different transitional metal ions, it was found that the Orn chip was the best of affinity binding and stability by which Zn2+ was the best metal ion for affinity while Co2+ was the best metal ion for stability. Thus, this protein microarray can be alternatively used as a high throughput screening method for rapid detection against SARS CoV 3CLpro and/or efficient purification of other Tagged proteins.


Anatomy of a pandemic: Emergency departments woefully unprepared for bird flu outbreak


title: Co-infection of SARS-CoV-2 and Influenza virus in Early Stage of the COVID-19 Epidemic in Wuhan, China

text: • Of the 1001 influenza positive samples, 3 outpatients and 1 inpatient were co-infected with SARS-CoV-2 in Wuhan in January, 2020. • Clinical and laboratory features indicate the 3 outpatients showed mild symptoms, and the inpatient experienced malignant tumor and had worse outcomes from COVID-19. • In January, when the testing capacity is insufficient, co-infection of SARS-CoV-2 with influenza viruses in winter influenza activity peak season may contribute the expansion of SARS-CoV-2 in the local population.


Exported Wuhan Novel Coronavirus Infection: An Expected Rate with Reference to Main Destination of Chinese Tourist, Thailand


title: Active screening and surveillance in the United Kingdom for Middle East respiratory syndrome coronavirus in returning travellers and pilgrims from the Middle East: a prospective descriptive study for the period 2013–2015

text: Summary Background Over 25000 pilgrims from the UK visit Saudi Arabia every year for the Umrah and Hajj pilgrimages. The recent outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in South Korea and the continuing reports of MERS-CoV cases from Saudi Arabia highlight the need for active surveillance for MERS-CoV in returning pilgrims or travellers from the Middle East. Public Health England Birmingham Laboratory (PHEBL) is one of a few selected UK public health laboratories responsible for MERS-CoV screening in travellers returning to the UK from the Middle East who present to hospital with severe respiratory symptoms. The results of the PHEBL MERS-CoV screening and surveillance over the past 3 years is presented. Methods UK travellers/pilgrims who returned from the Middle East and presented to a hospital with respiratory symptoms were studied over the period February 1, 2013 to December 31, 2015. Patients with respiratory symptoms, who satisfied the Public Health England MERS-CoV case algorithm, were tested for MERS-CoV and other respiratory tract viruses on admission to hospital. Results Two hundred and two patients suspected of having MERS-CoV were tested. None of them had a laboratory-confirmed MERS-CoV infection. A viral aetiology was detected in half (50.3%) of the cases, with rhinoviruses, influenza A (H1N1 and H3N2), and influenza B being most frequent. Peak testing occurred following the annual Hajj season and in other periods of raised national awareness. Conclusions Respiratory tract infections in travellers/pilgrims returning to the UK from the Middle East are mainly due to rhinoviruses, influenza A, and influenza B. Whilst MERS-CoV was not detected in the 202 patients studied, heightened awareness of the possibility of MERS-CoV and continuous proactive surveillance are essential to rapidly identify cases of MERS-CoV and other seasonal respiratory tract viruses such as avian influenza, in patients presenting to hospital. Early identification and isolation may prevent outbreaks in nosocomial settings.


title: Campylobacter Jejuni and Cytopenias

text: Abstract Background Leukopenia and thrombocytopenia in a febrile patient are not uncommon and may be a diagnostic clue in patients without an alternative explanation for cytopenias. This has not been reported in Campylobacter jejuni infections. Methods A healthy patient with fever, rigors, and an acute diarrheal illness was noted to have a white blood cell count of 2.65 × 109/L and platelet level of 125 × 109/L. Retrospective chart review of all adult C. jejuni stool-positive cases admitted over 1 year revealed leukopenia in 6 of 20 (30%), thrombocytopenia in 5 of 20 (25%), and both in 1 of 20 (5%). Results Cytopenias were mild, transient, and not associated with prolonged hospital stay or complications. Conclusions Acute C. jejuni infections should be added to the differential diagnosis of acute febrile illnesses that may be associated with leukopenia or thrombocytopenia. Cytopenias can be an important diagnostic clue in febrile illnesses, and their differential is presented.


title: Utilisation of and Attitude towards Traditional and Complementary Medicine among Ebola Survivors in Sierra Leone

text: Background and objectives: In addition to conventional healthcare, Ebola survivors are known to seek traditional and complementary healthcare (T&CM) options to meet their healthcare needs. However, little is known about the general beliefs of Ebola survivors regarding T&CM and the impact of these beliefs in influencing their decisions around T&CM use. This study examines Ebola survivors’ attitudes towards T&CM use in Sierra Leone. Materials and Methods: We conducted a nationwide quantitative cross-sectional study of 358 Ebola survivors in Sierra Leone between January and August 2018. We used descriptive analysis, chi-square tests and backward stepwise binary logistic regression for data analysis. Results: Close to half of the survivors (n = 163, 45.5%) had used T&CM since their discharge from an Ebola treatment centre. Survivors who viewed T&CM as boosting their immune system/resistance were 3.89 times (95%CI: 1.57–9.63, p = 0.003) more likely to use T&CM than those who did not view T&CM as boosting their immune system/resistance. Additionally, survivors who viewed T&CM as having fewer side effects than conventional medicine were more likely to use T&CM [OR = 5.03 (95%CI: 1.92–13.19, p = 0.001)]. Ebola survivors were more influenced to use T&CM based on their personal experience of the effectiveness of T&CM than by clinical evidence [OR = 13.72 (95%CI: 6.10–30.84, P < 0.001)]. Ebola survivors who perceived T&CM as providing them with more control than conventional medicine over their health/body were more likely to use T&CM [OR = 4.15 (95%CI: 1.74–9.89, p = 0.001)] as opposed to those who did not perceive T&CM in this way. Conclusions: Considering the widespread use of T&CM, an understanding of Ebola survivors’ attitudes/beliefs towards T&CM is useful to healthcare providers and policymakers with regard to public education and practitioner–survivors communication, T&CM regulation and research in Sierra Leone. Ebola survivors appear to turn to T&CM not only for treatment, but also to fill gaps in conventional health care services.


title: Detection of diverse viruses in alimentary specimens of bats in Macau

text: Bats carry a variety of viruses, and some of them cause public health problems. Macau, which is famous for its gambling industry, has a complex population structure. The globalization in such an international metropolis has enhanced the chance of disease transmission. Therefore, surveillance of zoonotic viruses is necessary for the early warning of potential emerging infectious diseases. Here, we report the first surveillance of bat viruses in Macau. In this study, we collected 1004 samples involving 10 bat species from 7 sites from April 2015 to May 2016, and examined the presence of viruses using nucleic acid-based methods. Coronaviruses, adenoviruses and paramyxoviruses were detected in these samples, with a high prevalence of coronaviruses. While, none was positive for hepatitis A virus, hepatitis E virus or hantavirus. Co-infections are not common in those bat species, but coronavirus HKU6 and adenovirus can be found commonly occurred in Myotis ricketti.


title: Treatment of primary and metastatic peritoneal tumors in the Covid-19 pandemic

text: Abstract The Covid-19 pandemic is profoundly changing the organization of healthcare access. This is particularly so for peritoneal neoplastic diseases, for which curative treatment mobilizes substantial personnel, operating room and intensive care resources. The BIG-RENAPE and RENAPE groups have made tentative proposals for prioritizing care provision. A tightening of the usual selection criteria is needed for curative care: young patients with few or no comorbidities and limited peritoneal extension. It is desirable to prioritize disease conditions for which cytoreduction surgery with or without associated hyperthermic intraoperative peritoneal chemotherapy (HIPEC) is the gold-standard treatment, and for which systemic chemotherapy cannot be a temporary or long-term alternative: pseudomyxoma peritonei, resectable malignant peritoneal mesotheliomas, peritoneal metastases of colorectal origin if they are resectable and unresponsive to systemic chemotherapy after up to 12 courses, first-line ovarian carcinomatosis if resectable or in interval surgery after at most six courses of systemic chemotherapy. Addition of HIPEC must be discussed case by case in an expert center. The prioritization of indications must consider local conditions and the phase of the epidemic to allow optimal peri-operative care.


title: Diarrhea: an underestimated symptom in coronavirus disease 2019

text: In a retrospective study in the Nord Franche-Comté hospital conducted between March 1st and March 17th 2020, and compared to the review of Li et al., diarrhea was a main symptom in patients with COVID-19. Out of the 114 patients, 55 (48%) had diarrhea; it was the fifth most common symptom. In the group of patients with diarrhea, the median age was 56 years (± 18) and 32 (58%) were female. Only 2 patients (3.6%) had a past history of inflammatory bowel disease. Fifty-six percent of patients (n = 30/54) were hospitalised. Diarrhea appeared 4.5 days (± 1.8) after the onset of the first other symptoms in COVID-19. Of the 55 patients with diarrhea, 29 (52.7%) had at least one simultaneous gastrointestinal (GI) symptom other than diarrhea. Twenty-five patients (45.5%) had nausea, 19 patients (34.5%) had abdominal pain and 9 (16.3%) had vomiting. Myalgia, sore throat, sneezing and the other GI symptoms were statistically more frequent in the group with diarrhea than in the group without diarrhea (P < 0.05).


Importance of the One Health approach to study the SARS-CoV-2 in Latin America


title: Employment and Compliance with Pandemic Influenza Mitigation Recommendations

text: In the event of a serious pandemic influenza outbreak, businesses must play a key role in protecting employees' health and safety. With regard to pandemic influenza mitigation recommendations requiring social distancing, we examined whether some US employees would disproportionately fail to comply because of job insecurity and financial problems associated with missing work. We used the 2006 Harvard School of Public Health Pandemic Influenza Survey and multivariable logistic regression to determine whether employment characteristics such as inability to work from home, lack of pay when absent from work, and self-employment would be associated with less ability to comply with recommendations. We found that inability to work from home, lack of paid sick leave, and income are associated with working adults’ ability to comply and should be major targets for workplace interventions in the event of a serious outbreak.


title: Human Mobility and the Global Spread of Infectious Diseases: A Focus on Air Travel

text: Greater human mobility, largely driven by air travel, is leading to an increase in the frequency and reach of infectious disease epidemics. Air travel can rapidly connect any two points on the planet, and this has the potential to cause swift and broad dissemination of emerging and re-emerging infectious diseases that may pose a threat to global health security. Investments to strengthen surveillance, build robust early-warning systems, improve predictive models, and coordinate public health responses may help to prevent, detect, and respond to new infectious disease epidemics.


title: Plant polyphenols as dietary antioxidants in human health and disease

text: Polyphenols are secondary metabolites of plants and are generally involved in defense against ultraviolet radiation or aggression by pathogens. In the last decade, there has been much interest in the potential health benefits of dietary plant polyphenols as antioxidant. Epidemiological studies and associated meta-analyses strongly suggest that long term consumption of diets rich in plant polyphenols offer protection against development of cancers, cardiovascular diseases, diabetes, osteoporosis and neurodegenerative diseases. Here we present knowledge about the biological effects of plant polyphenols in the context of relevance to human health.


title: Mumps Virus: Modification of the Identify-Isolate-Inform Tool for Frontline Healthcare Providers

text: Mumps is a highly contagious viral infection that became rare in most industrialized countries following the introduction of measles-mumps-rubella (MMR) vaccine in 1967. The disease, however, has been re-emerging with several outbreaks over the past decade. Many clinicians have never seen a case of mumps. To assist frontline healthcare providers with detecting potential cases and initiating critical actions, investigators modified the “Identify-Isolate-Inform” tool for mumps infection. The tool is applicable to regions with rare incidences or local outbreaks, especially seen in college students, as well as globally in areas where vaccination is less common. Mumps begins with a prodrome of low-grade fever, myalgias and malaise/anorexia, followed by development of nonsuppurative parotitis, which is the pathognomonic finding associated with acute mumps infection. Orchitis and meningitis are the two most common serious complications, with hearing loss and infertility occurring rarely. Providers should consider mumps in patients with exposure to a known case or international travel to endemic regions who present with consistent signs and symptoms. If mumps is suspected, healthcare providers must immediately implement standard and droplet precautions and notify the local health department and hospital infection control personnel.


title: An adult model of exclusive viral wheeze: inflammation in the upper and lower respiratory tracts

text: Background We have previously reported an experimental infection of young adults with a history of episodic and exclusive viral wheeze (EVW) using human coronavirus, in which 16 of 24 with EVW (15 atopic) and 11 of 19 healthy controls (seven atopic) developed a symptomatic cold with evidence of infection, but only those with EVW developed lower respiratory tract symptoms and increased airway responsiveness. Objective The aim of this study was to compare the EVW and control groups from this study for inflammatory changes occurring in the upper and lower respiratory tracts during the experimental infection, in particular, to determine whether eosinophil‐driven inflammation was associated with EVW. Methods Nasal lavage and induced sputum were collected prior to inoculation (day 0) and 2, 4 and 17 days later. Differential cell counts were performed and supernatant was assayed for IL‐8, IL‐5, IFN‐γ, and eosinophilic cationic protein (ECP). Results There was no difference between the two groups in any measurement at baseline. In both groups, during colds the volume of nasal secretion increased as did leucocyte counts in both upper and lower respiratory tracts. A modest increase in nasal neutrophil count was seen in both EVW and control groups with symptomatic colds on day 2 (median (quartile) difference from baseline 5.4 (0.0, 11.0) and 1.8 (−1.1, 2.2)×10(4)/mL of secretions, respectively). The change in nasal neutrophil counts in all subjects correlated with nasal symptom scores. A significant relative increase in sputum differential neutrophil count was seen on day 4 in the EVW group with a cold but not in controls (mean difference (95% confidence interval) 20.4 (9.6, 31.1)% and 3.1 (−8.2, 14.5)%, respectively, P<0.01); however, this increase did not correlate with lower respiratory tract symptom scores. IL‐8 increased in both the upper and lower respiratory tracts in both EVW and control subjects with colds, the largest change being seen on day 4 in the sputum of those with EVW (mean difference from baseline (95% confidence interval) 2.5 (0.55–4.46) ng/mL). Only modest changes were seen in IFN‐γ and no changes were seen in IL‐5 or ECP. None of the results was influenced by the atopic status of the subjects in either group. Conclusions EVW wheeze is characterized by neutrophilic inflammation in both the upper and lower respiratory tracts without eosinophilia (even in atopic subjects). IL‐8 is likely to be an important chemokine in this process. Symptoms and airway responsiveness were correlated with change in neutrophils.


title: Mental health and psychosocial well-being during the COVID-19 pandemic: the invisible elephant in the room

text: The novel SARS-CoV-2 coronavirus pandemic has emerged as a truly formidable threat to humankind’s existence. In the wake of the massively volatile global situation created by COVID-19, it is vital to recognize that the trauma it causes can affect people in different ways, at the individual and collective levels, resulting in mental health challenges for many. Although mental health problems account for about one-third of the world’s disability among adults, these issues tend to be under-addressed and overlooked in society and are closely associated with deadly disease outbreaks. In large scale outbreaks, the mental health problems experienced are not limited to infected persons but also extend to involve frontline health workers and community members alike. While it is crucial to limit the spread of infections during an outbreak, previous experience suggests that mental and behavioural health interventions should be fully included in public health response strategies.


title: New immunization strategies: adapting to global challenges

text: Immunization has made an enormous contribution to global health. Global vaccination coverage has dramatically improved and mortality rates among children due to vaccine-preventable diseases have been significantly reduced since the creation of the Expanded Programme of Immunization in 1974, the formation of Gavi, the Vaccine Alliance, in 2000, and the development of the Global Vaccine Action Plan in 2012. However, challenges remain and persisting inequities in vaccine uptake contribute to the continued occurrence and outbreaks of vaccine-preventable diseases. Inequalities in immunization coverage by geography, urban-rural, and socio-economic status jeopardize the achievement of global immunization goals and call for renewed immunization strategies. These should take into account emerging opportunities for building better immunization systems and services, as well as the development of new vaccine products and delivery technologies. Such strategies need to achieve equity in vaccination coverage across and within countries. This will require the participation of communities, a better understanding of vaccine acceptance and hesitancy, the expansion of vaccination across the life course, approaches to improve immunization in middle-income countries, enhanced use of data and possible financial and non-financial incentives. Vaccines also have an important role to play in comprehensive disease control, including the fight against antimicrobial resistance. Lessons learned from disease eradication and elimination efforts of polio, measles and maternal and neonatal tetanus are instrumental in further enhancing global immunization strategies in line with the revised goals and targets of the new Immunization Agenda 2030, which is currently being developed.


title: Effect of ambient air pollutants and meteorological variables on COVID-19 incidence

text: OBJECTIVE: To determine whether ambient air pollutants and meteorological variables are associated with daily COVID-19 incidence. DESIGN: A retrospective cohort from January 25 to February 29, 2020. SETTING: Cities of Wuhan, Xiaogan, and Huanggang, China. PATIENTS: The COVID-19 cases detected each day. METHODS: We collected daily data of COVID-19 incidence, 8 ambient air pollutants (particulate matter of ≤2.5 µm [PM(2.5)], particulate matter ≤10 µm [PM(10)], sulfur dioxide [SO(2)], carbon monoxide [CO], nitrogen dioxide [NO(2)], and maximum 8-h moving average concentrations for ozone [O(3)-8h]) and 3 meteorological variables (temperature, relative humidity, and wind) in China’s 3 worst COVID-19–stricken cities during the study period. The multivariate Poisson regression was performed to understand their correlation. RESULTS: Daily COVID-19 incidence was positively associated with PM(2.5) and humidity in all cities. Specifically, the relative risk (RR) of PM(2.5) for daily COVID-19 incidences were 1.036 (95% confidence interval [CI], 1.032–1.039) in Wuhan, 1.059 (95% CI, 1.046–1.072) in Xiaogan, and 1.144 (95% CI, 1.12–1.169) in Huanggang. The RR of humidity for daily COVID-19 incidence was consistently lower than that of PM(2.5), and this difference ranged from 0.027 to 0.111. Moreover, PM(10) and temperature also exhibited a notable correlation with daily COVID-19 incidence, but in a negative pattern The RR of PM(10) for daily COVID-19 incidence ranged from 0.915 (95% CI, 0.896–0.934) to 0.961 (95% CI, 0.95–0.972, while that of temperature ranged from 0.738 (95% CI, 0.717–0.759) to 0.969 (95% CI, 0.966–0.973). CONCLUSIONS: Our data show that PM(2.5) and humidity are substantially associated with an increased risk of COVID-19 and that PM(10) and temperature are substantially associated with a decreased risk of COVID-19.


title: EVOLUTION OF HOST SPECIFICITY DRIVES REPRODUCTIVE ISOLATION AMONG RNA VIRUSES

text: Ecological speciation hypotheses claim that assortative mating evolves as a consequence of divergent natural selection for ecologically important traits. Reproductive isolation is expected to be particularly likely to evolve by this mechanism in species such as phytophagous insects that mate in the habitats in which they eat. We tested this expectation by monitoring the evolution of reproductive isolation in laboratory populations of an RNA virus that undergoes genetic exchange only when multiple virus genotypes coinfect the same host. We subjected four populations of the RNA bacteriophage φ6 to 150 generations of natural selection on a novel host. Although there was no direct selection acting on host range in our experiment, three of the four populations lost the ability to infect one or more alternative hosts. In the most extreme case, one of the populations evolved a host range that does not contain any of the hosts infectible by the wild‐type φ6. Whole genome sequencing confirmed that the resulting reproductive isolation was due to a single nucleotide change, highlighting the ease with which an emerging RNA virus can decouple its evolutionary fate from that of its ancestor. Our results uniquely demonstrate the evolution of reproductive isolation in allopatric experimental populations. Furthermore, our data confirm the biological credibility of simple “no‐gene” mechanisms of assortative mating, in which this trait arises as a pleiotropic effect of genes responsible for ecological adaptation.


Nicaragua's response to COVID-19 – Authors' reply


title: An early test and treat strategy for SARS-CoV-2

text: As COVID-19 cases and deaths continue to expand globally, there is an urgent need to develop, test and approve effective antiviral therapies. Currently a majority of clinical trials are evaluating therapies in patients who are already hospitalized with SARS Co-V-2 infection. Given that the median time between development of symptoms and need for hospitalization is a week, a golden opportunity to intervene early is being missed. Indeed, for many other viral infections, early treatment soon after development of symptoms is associated with decreased mortality, lower hospitalization rates and lower likelihood of transmission to others. Here, we advocate for randomized double-blind placebo controlled clinical trials to evaluate promising agents early during SARS Co-V-2 infection.


title: Aminopeptidase inhibitors bestatin and actinonin inhibit cell proliferation of myeloma cells predominantly by intracellular interactions

text: Abstract The antiproliferative effects of bestatin and actinonin on U937 and K562 cells have been compared with their inhibitory activity on cell surface aminopeptidases. The results strongly suggest that the inhibition of cell surface aminopeptidases cannot be the main reason for the inhibition of cell proliferation. This was confirmed by studying the effect of buthionine sulfoximine (BSO), MK-571 (3-([{3-(2-[7-chloro-2-quinolinyl]-ethenyl)-phenyl}-{(3-dimethyl-amino-3-oxopropyl)-thio}-methyl]thio)propanoic acid) and verapamil on the inhibition of cell proliferation by bestatin and actinonin. BSO and MK-571, which inhibit the efflux of drugs mediated by multidrug resistance-associated protein (MRP), increased the action of both inhibitors, indicating that the latter enter the cells and that their export is mediated by MRP in both cell lines. Verapamil significantly increased the inhibitory activity of bestatin on K562 cells, indicating that the intracellular concentration of bestatin can be mediated also by P-glycoprotein.


title: A multiplex real-time PCR assay for detection of oseltamivir-resistant strains of influenza virus

text: Influenza is a contagious disease of humans and animals caused by viruses belonging to the Orthomyxoviridae family. The influenza A virus genome consists of negative sense, single-stranded, segmented RNA. Influenza viruses are classified into subtypes based on two surface antigens known as hemagglutinin (H) and neuraminidase (N). The main problem with influenza A viruses infecting humans is drug resistance, which is caused by antigenic changes. A few antiviral drugs are available, but the most popular is the neuraminidase inhibitor — oseltamivir. The resistance against this drug has probably developed through antigenic drift by a point mutation in one amino acid at position 275 (H275Y). In order to prevent a possible influenza pandemic it is necessary to develop fast diagnostic tests. The aim of this project was to develop a new test for detection of influenza A virus and determination of oseltamivir resistance/sensitivity in humans. Detection and differentiation of oseltamivir resistance/sensitivity of influenza A virus was based on real-time PCR. This test contains two TaqMan probes, which work at different wavelengths. Application of techniques like multiplex real-time PCR has greatly enhanced the capability for surveillance and characterization of influenza viruses. After its potential validation, this test can be used for diagnosis before treatment.


title: Long-term immunogenicity of an AS03-adjuvanted influenza A(H1N1)pdm09 vaccine in young and elderly adults: An observer-blind, randomized trial

text: Abstract Background This study (NCT00979602) evaluated the immunogenicity and relative protective efficacy of one dose of influenza A(H1N1)pdm09 vaccine with or without AS03 (an α-tocopherol oil-in-water emulsion based Adjuvant System). Methods Four thousands and forty-eight healthy adults aged ≥18 years were randomized (1:1) to receive one dose of either the adjuvanted split virion (3.75μg hemagglutinin antigen [HA]/AS03) or non-adjuvanted (15μg HA) vaccine. Hemagglutination inhibition [HI] antibody response was evaluated before vaccination and at Days 21, 42 and 182 (Month 6). Safety of the study vaccines was evaluated during the entire study duration. Results At Day 21, both study vaccines induced HI immune responses meeting the US regulatory criteria in subjects 18–64 years (seroprotection rate [SPR]: 98.0% [97.1–98.6]; seroconversion rate [SCR]: 89.7% [88.0–91.2] in the AS03-adjuvanted group; SPR: 91.4% [89.9–92.8]; SCR: 74.6% [72.3–76.9] in the non-adjuvanted group) and >64 years of age (SPR: 86.0% [82.5–89.0]; SCR: 75.3% [71.1–79.2] in the AS03-adjuvanted group; SPR: 69.1% [64.6–73.3]; SCR: 56.7% [52.0–61.3] in the non-adjuvanted group). The AS03-adjuvanted vaccine induced higher HI geometric mean titers than the non-adjuvanted vaccine at all time points. At Month 6, only subjects 18–64 years of age from both vaccine groups still met the US regulatory criteria (SPR: 82.1% [80.0–84.1]; SCR: 62.3% [59.6–64.8] in the AS03-adjuvanted group; SPR: 75.3% [72.9–77.5]; SCR: 53.7% [51.0–56.4] in the non-adjuvanted group). Protective efficacy was not evaluated due to low number of RT-qPCR-confirmed A(H1N1)pdm09 influenza cases. Through Month 12, 216 serious adverse events (in 157 subjects: 84 in the AS03-adjuvanted and 73 in the non-adjuvanted group) and 12 potentially immune mediated diseases (5 in the AS03-adjuvanted and 7 in the non-adjuvanted group) were reported. Conclusion A single dose of either adjuvanted or non-adjuvanted influenza A(H1N1)pdm09 vaccine induced protective HI antibody levels against the A/California/7/2009 strain that persisted through Month 6 in the 18–64 years population.


Correction to Lancet Gastroenterol Hepatol 2020; 5: 667–68


title: AIK-C measles vaccine expressing fusion protein of respiratory syncytial virus induces protective antibodies in cotton rats

text: Abstract Respiratory syncytial virus (RSV) is the most common cause of respiratory infection in infants, and no vaccine is available. In this report, recombinant AIK-C measles vaccines, expressing the RSV G or F protein of subgroup A (MVAIK/RSV/G or F), were investigated as a RSV vaccine candidate. MVAIK/RSV/G or F had the original ts phenotype and expressed RSV/G or F protein. Cross-reactive neutralizing antibodies against RSV subgroups A and B were detected in cotton rats immunized intramuscularly with MVAIK/RSV/F but not MVAIK/RSV/G. In cotton rats infected with RSV, RSV was recovered and lung histopathological finding was compatible with interstitial pneumonia, demonstrating thickening of alveolar walls and infiltration of mononuclear cells. When cotton rats immunized with MVAIK/RSV/F were challenged with homologous RSV subgroup A, no infectious RSV was recovered and very mild inflammation was noted without RSV antigen expression. When they were challenged with subgroup B, protective efficacy decreased. When cotton rats immunized with MVAIK/RSV/G were challenged with RSV subgroup A, low levels of infectious virus were recovered from lung. When challenged with subgroup B, no protective effects was demonstrated, demonstrating large amounts of RSV antigen in bronchial-epithelial cells. MVAIK/RSV/F is promising candidate and protective effects should be confirmed in monkey model.


Novel hepacivirus in Asian house shrew, China


Agri-food tech discovers silver linings in the pandemic


title: Acute pulmonary embolism in non-hospitalized COVID-19 patients referred to CTPA by emergency department

text: OBJECTIVES: To evaluate the prevalence of acute pulmonary embolism (APE) in non-hospitalized COVID-19 patients referred to CT pulmonary angiography (CTPA) by the emergency department. METHODS: From March 14 to April 6, 2020, 72 non-hospitalized patients referred by the emergency department to CTPA for COVID-19 pneumonia were retrospectively identified. Relevant clinical and laboratory data and CT scan findings were collected for each patient. CTPA scans were reviewed by two radiologists to determinate the presence or absence of APE. Clinical classification, lung involvement of COVID-19 pneumonia, and CT total severity score were compared between APE group and non-APE group. RESULTS: APE was identified in 13 (18%) CTPA scans. The mean age and D-dimer of patients from the APE group were higher in comparison with those from the non-APE group (74.4 vs. 59.6 years, p = 0.008, and 7.29 vs. 3.29 μg/ml, p = 0.011). There was no significant difference between APE and non-APE groups concerning clinical type, COVID-19 pneumonia lung lesions (ground-glass opacity: 85% vs. 97%; consolidation: 69% vs. 68%; crazy paving: 38% vs. 37%; linear reticulation: 69% vs. 78%), CT severity score (6.3 vs. 7.1, p = 0.365), quality of CTPA (1.8 vs. 2.0, p = 0.518), and pleural effusion (38% vs. 19%, p = 0.146). CONCLUSIONS: Non-hospitalized patients with COVID-19 pneumonia referred to CT scan by the emergency departments are at risk of APE. The presence of APE was not limited to severe or critical clinical type of COVID-19 pneumonia. KEY POINTS: • Acute pulmonary embolism was found in 18% of non-hospitalized COVID-19 patients referred by the emergency department to CTPA. Two (15%) patients had main, four (30%) lobar, and seven (55%) segmental acute pulmonary embolism. • Five of 13 (38%) patients with acute pulmonary embolism had a moderate clinical type. • Severity and radiological features of COVID-19 pneumonia showed no significant difference between patients with or without acute pulmonary embolism.


Décision kinésithérapique : Éric 0. 55 ans. En réanimation avec Covid-19


title: Maintaining mental health in the time of coronavirus

text: From social isolation to working on the front line, covid-19 is posing serious challenges to mental health. Moya Sarner asks the experts how we can protect ourselves


title: Tumor suppressor p53 inhibits porcine epidemic diarrhea virus infection via interferon-mediated antiviral immunity

text: Abstract p53 is a tumor suppressor gene that can be activated in many contexts, such as DNA damage or stressful conditions. p53 has also been shown to be important for responses to certain viral infections. Porcine epidemic diarrhea virus (PEDV) is a major enteric pathogen of the coronavirus family that causes extensive mortality among piglets. The involvement of p53 during PEDV infection has not previously been investigated. In this study, we detected p53 upregulation in response to PEDV infection. Treatment with a p53 specific activator or p53 overexpression markedly decreased viral replication, and we showed that there was more viral progeny produced in p53 knock-out cells than in p53 wild-type cells. Finally, we demonstrated that inhibition of viral infection by p53 was mediated via p53-dependent IFN signaling, leading to IFN-stimulated response element (ISRE) activation, as well as the upregulation of IFN-stimulated genes (ISGs) and IFN-β released from infected cells. These findings demonstrate that p53 suppresses PEDV infection, offering a novel therapeutic strategy for combatting this deadly disease in piglets.


Alveolar levels of immuno-inflammatory mediators in diffuse alveolar hemorrhage after allogeneic transplant


Molecular mechanisms of viral infection and propagation: An overview of the second Advanced Summer School in Africa


title: Transmission and clinical characteristics of coronavirus disease 2019 in 104 outside‐Wuhan patients, China

text: OBJECTIVE: Cases with coronavirus disease 2019 (COVID‐19) emigrated from Wuhan escalated the risk of spreading in other cities. This report focused on the outside‐Wuhan patients to assess the transmission and clinical characteristics of this illness. METHODS: Contact investigation was conducted on each patient who admitted to the assigned hospitals in Hunan Province (geographically adjacent to Wuhan) from Jan 22, 2020 to Feb 23, 2020. Patients were confirmed by PCR test. Demographic, clinical and outcomes were collected and analyzed. RESULTS: Of the 104 patients, 48 (46.15%) were imported cases who were immigrated from Wuhan; 93 (89.42%) had a definite contact history with infections. Family clusters were the major body of patients. Transmission along the chain of 3 “generations” was observed. Five asymptomatic infections were found and 2 of them infected their relatives. Mean age was 43 (rang, 8‐84) years and 49 (47.12%) were male. The median incubation period was 6 (rang, 1‐32) days, of 8 patients ranged from 18 to 32 days, 96 (92.31%) discharged and 1 (0.96%) died. Average hospital stay was 10 (rang, 8‐14) days. CONCLUSIONS: Family but not community transmission occupied the main body of infections in the two centers, suggesting the timely control measures after the Wuhan shutdown wok well. Asymptomatic transmission demonstrated here warned us that it may bring more risk to the spread of COVID‐19. A 14‐day quarantine may need to be prolonged. This article is protected by copyright. All rights reserved.


title: Cardiac surgery in patients with confirmed COVID‐19 infection: Early experience

text: The novel coronavirus, now termed SARS‐CoV‐2, has caused a significant global impact in the space of 4 months. Almost all elective cardiac surgical operations have been postponed in order to reduce transmission and to allocate resources adequately. Urgent and emergency cardiac surgery is still taking place during the pandemic. The decision to operate in urgent patients with active/recent COVID‐19 infection is difficult to make, particularly as it is still an unknown disease entity in the setting of emergent cardiac surgery. We present a case series of three patients who underwent urgent cardiac surgery and who have had recent or active COVID‐19 infection.


title: Treatment of Community-Acquired Pneumonia: Are All Countries Treating Children in the Same Way? A Literature Review

text: BACKGROUND: Pneumonia represents an important threat to children's health in both developed and developing countries. In the last 10 years, many national and international guidelines on the treatment of pediatric CAP have been published, in order to optimize the prescription of antibiotics and limit their cost and side effects. However, the practical implementation of these guidelines is still limited. MAIN TEXT: We analyzed the current recommendations for the therapy of pediatric community-acquired pneumonia (CAP) that all converge on the identification of aminopenicillins and beta-lactams as the optimal treatment for CAP. We also conducted a review of the current literature on antibiotic regimens used for pediatric CAP to identify the current state of guidelines implementation in different settings. We selected 37 studies published from 2010 to 2016, including both retrospective and prospective studies, mainly cross-sectional and hospital based. The results show a global heterogeneity in the antibiotics prescription for pediatric CAP, with application of guidelines varying from 0% to more than 91% and with important differences even within the same country. CONCLUSIONS: Our review has demonstrated that the implementation of the guidelines is still limited but also that achieving the optimal prescription is possible and can be done in both developed and developing countries.


title: Managing COVID‐19 in Renal Transplant Recipients: A Review of Recent Literature and Case Supporting Corticosteroid‐sparing Immunosuppression

text: Novel coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome virus (SARS‐CoV‐2) has become a global health care crisis. The Centers for Disease Control and Prevention (CDC) lists immunocompromised patients, including those requiring immunosuppression following renal transplantation, as high risk for severe disease from SARS‐CoV‐2. Treatment for other viral infections in renal transplant recipients often includes a reduction in immunosuppression; however, no current guidelines are available recommending the optimal approach to managing immunosuppression in the patients who are infected with SARS‐CoV‐2. It is currently advised to avoid corticosteroids in the treatment of SARS‐CoV‐2 outside of critically ill patients. Recently published cases describing inpatient care of COVID‐19 in renal transplant recipients differ widely in disease severity, time from transplantation, baseline immunosuppressive therapy, and the modifications made to immunosuppression during COVID‐19 treatment. This review summarizes and compares inpatient immunosuppressant management strategies of recently published reports in the renal transplant population infected with SARS‐CoV‐2 and discusses the limitations of corticosteroids in managing immunosuppression in this patient population.


title: Diagnosis of COVID‐19 infection in children: less nasopharyngeal swabs, more saliva

text: We read with great interest the article by Jonas F. Ludvigsson on COVID‐19 infection in Children (1). He conducted a systematic literature review to identify papers on COVID‐19. The conclusion was that COVID‐19 infection can occur in children, but they seemed to have a lower incidence as well as a milder disease course and better prognosis than adults.


title: El papel del dermatólogo en el diagnóstico precoz de la artritis psoriásica: recomendaciones de un grupo de expertos

text: Psoriatic arthritis is a common type of inflammatory arthritis found in 40% of patients with psoriasis. Because skin involvement usually precedes joint involvement, dermatologists play a key role in early detection. Early diagnosis is important for reducing the risk of irreversible structural damage, attenuating the deterioration of physical function, and improving patients’ quality of life. This consensus statement was drafted by a group of 9 dermatologists and 1 rheumatologist to provide simple recommendations to help dermatologists screen for psoriatic arthritis in patients with psoriasis. The experts offer consensus-based guidelines that draw on a review of available scientific evidence and on experience acquired in routine clinical practice.


Please cite this paper as: He et al. (2013) Amaryllidaceae alkaloids inhibit nuclear‐to‐cytoplasmic export of ribonucleoprotein (RNP) complex of highly pathogenic avian influenza virus H5N1. Influenza and Other Respiratory Viruses 7(6), 922–931. Background Few drugs are currently licensed to treat influenza A infection, and new therapies are needed, especially for highly pathogenic strains. Traditional medicinal plants, such as Lycoris radiata, are a potential source of new antiviral agents. Objective To test 15 Amaryllidaceae alkaloids isolated from the bulbs of L. radiata in vitro for antiviral activities against influenza virus type A, A/Chicken/GuangDong/178/2004 (H5N1, 178). Methods Antiviral activities of the compounds were tested in time‐of‐addition assays, hemagglutination inhibition (HI) assays, neuraminidase (NA) activity assays, and viral entry inhibition assays using H5N1‐HIV pseudoviruses. Effects of the compounds on localization and activity of the viral ribonucleoprotein (RNP) were determined by immunofluorescence and an RNP minigenome assay, respectively. Results Among the alkaloids, lycorine (AA1), hippeastrine (AA2), hemanthamine (AA3) and 11‐hydroxy vittatine (AA4) exhibited antiviral activities, with EC(90) values of 0·52, 82·07, 4·15, and 13·45 μm, respectively. These compounds did not affect the function of the outer membrane proteins or the viral entry process and viral RNP activity. As AA1 and AA3 exhibited stronger antiviral activities, they were further analyzed. Intracellular nucleoprotein (NP) localization showed that AA1 and AA3 inhibited the RNP complex in the nucleus at an early stage of a single‐round and multi‐round of replication. Conclusion Four Amaryllidaceae alkaloids were first determined that could exert anti‐influenza activities after virus entry into cells. Furthermore, AA1 and AA3 could inhibit nuclear‐to‐cytoplasmic export of the RNP complex of virus replication. Thus, these compounds may be developed further as anti‐influenza drug candidates.


title: 5′-O-Masked 2′-deoxyadenosine analogues as lead compounds for hepatitis C virus (HCV) therapeutic agents

text: Abstract On the basis of our previous study on antiviral agents against the severe acute respiratory syndrome (SARS) coronavirus, a series of nucleoside analogues whose 5′-hydroxyl groups are masked by various protective groups such as carboxylate, sulfonate, and ether were synthesized and evaluated to develop novel anti-hepatitis C virus (HCV) agents. Among these, several 5′-O-masked analogues of 6-chloropurine-2′-deoxyriboside (e.g., 5′-O-benzoyl, 5′-O-p-methoxybenzoyl, and 5′-O-benzyl analogues) were found to exhibit effective anti-HCV activity. In particular, the 5′-O-benzoyl analogue exhibited the highest potency with an EC50 of 6.1μM in a cell-based HCV replicon assay. Since the 5′-O-unmasked analogue (i.e., 6-chloropurine-2′-deoxyriboside) was not sufficiently potent (EC50 =47.2μM), masking of the 5′-hydroxyl group seems to be an effective method for the development of anti-HCV agents. Presently, we hypothesize two roles for the 5′-O-masked analogues: One is the role as an anti-HCV agent by itself, and the other is as a prodrug of its 5′-O-demasked (deprotected) derivative.


title: COVID‐19 risk triage: Engaging residents in telephonic screening

text: In response to the increased demand to screen patients with symptoms concerning for COVID-19, we created a risk assessment triage process for our internal medicine clinic that utilizes residents' clinical reasoning skills without direct exposure to high-risk patients.


title: From APOBEC to ZAP: Diverse mechanisms used by cellular restriction factors to inhibit virus infections

text: Abstract Antiviral restriction factors are cellular proteins that inhibit the entry, replication, or spread of viruses. These proteins are critical components of the innate immune system and function to limit the severity and host range of virus infections. Here we review the current knowledge on the mechanisms of action of several restriction factors that affect multiple viruses at distinct stages of their life cycles. For example, APOBEC3G deaminates cytosines to hypermutate reverse transcribed viral DNA; IFITM3 alters membranes to inhibit virus membrane fusion; MXA/B oligomerize on viral protein complexes to inhibit virus replication; SAMHD1 decreases dNTP intracellular concentrations to prevent reverse transcription of retrovirus genomes; tetherin prevents release of budding virions from cells; Viperin catalyzes formation of a nucleoside analogue that inhibits viral RNA polymerases; and ZAP binds virus RNAs to target them for degradation. We also discuss countermeasures employed by specific viruses against these restriction factors, and mention secondary functions of several of these factors in modulating immune responses. These important examples highlight the diverse strategies cells have evolved to combat virus infections.


title: CD154 Blockade and Donor-Specific Transfusions in DLA-Identical Marrow Transplantation in Dogs Conditioned with 1-Gy Total Body Irradiation

text: Abstract Stable mixed donor/host chimerism has been reliably established in dogs given a sublethal dose (2 Gy) of total body irradiation (TBI) before and immunosuppression with mycophenolate mofetil (MMF) or rapamycin combined with cyclosporine (CSP) after marrow transplantation from dog leukocyte antigen (DLA)-identical littermates (hematopoietic cell transplantation [HCT]). When TBI was reduced to 1 Gy, only transient engraftment was observed. Here we investigated whether stable engraftment after 1-Gy TBI could be accomplished by reducing host-versus-donor immune responsiveness through preceding CD154 blockade and infusion of donor peripheral blood mononuclear cells (PBMCs). We found that the anti-human CD154 antibody, 5c8, cross-reacted with canine lymphocytes and blocked alloimmune responses in vitro. Based on pharmacokinetic studies, 6 dogs received a single intravenous injection of 5 mg/kg anti-CD154 antibody (on day −5), followed 1 day later by donor PBMCs. On day 0, the dogs were given 1 Gy of TBI and underwent DLA-identical marrow grafts. Postgraft immunosuppression consisted of MMF and CSP. All 6 dogs demonstrated initial engraftment; 3 dogs sustained the engraftment for >26 weeks, whereas 3 dogs rejected their grafts, after 9, 22, and 24 weeks, and survived with autologous recovery. Graft survival was significantly improved over that in 11 historical controls conditioned with 1-Gy TBI and given either MMF or rapamycin with CSP after HCT, all of which rejected their grafts between 3 and 12 weeks (P = .03). Preceding donor PBMC infusion and CD154 blockade improved survival of DLA-identical marrow grafts after 1-Gy TBI.


title: Complete Genome Sequence of a Variant Porcine Epidemic Diarrhea Virus Strain Isolated in Central China

text: We report here the complete genome sequence of the porcine epidemic diarrhea virus strain CH/ZMDZY/11 isolated from central China. Our data, together with sequence data of porcine epidemic diarrhea virus (PEDV) isolates from other parts in China, will help to understand better the epidemiology and genetic diversity of PEDV field isolates in China.


title: Inaccurate conclusions by Tang and colleagues

text: I read with interest the study by Tang and colleagues, published March 27, 2020, entitled "Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease patients with coagulopathy." Unfortunately, this retrospective study came to conclusions that are inaccurate with the information provided. The authors use of the word "therapy" implies that patients were given therapeutic doses of anticoagulants, however, doses appear to be most consistent with prophylaxis dosing. The authors report that 94 patients received enoxaparin at 40-60mg/day. They did not specify the route of administration, subcutaneous (SC) or intravenous (IV), nor did they specify the percentage of patients that received which dose. The 40mg per day dose of enoxaparin given SC is the prophylactic dose. The 60mg per day IV dose would be therapeutic for patients weighing 40kg, not a typical weight for an adult patient.


title: The nsP3 Macro Domain is Important for Sindbis Virus Replication in Neurons and Neurovirulence in Mice

text: Sindbis virus (SINV), the prototype alphavirus, contains a macro domain in the highly conserved N-terminal region of nonstructural protein 3 (nsP3). However, the biological role of the macro domain is unclear. Mutations of amino acids 10 and 24 from asparagine to alanine in the ADP-ribose binding region of the macro domain impaired SINV replication and viral RNA synthesis particularly in neurons, but did not alter binding of poly(ADP-ribose). Mutation at position 10 had the greatest effect and caused nsP3 instability in neurons, decreased SINV-induced death of mature, but not immature neurons, and attenuated virulence in 2 week-old, but not 5 day-old mice. A compensatory mutation at amino acid 31 in the macro domain of nsP3, as well as reversion of mutated amino acid 10, occurred during replication of double mutant SINV in vitro and in vivo. The nsP3 macro domain is important for SINV replication and age-dependent susceptibility to encephalomyelitis.


title: Methylprednisolone pulse therapy for refractory Mycoplasma pneumoniae pneumonia in children

text: Summary Objectives To determine the efficacy of methylprednisolone pulse therapy for children with Mycoplasma pneumoniae pneumonia (MP) that is refractory to antibiotic treatment. Methods Refractory patients were defined as cases showing clinical and radiological deterioration despite appropriate antibiotic therapy for 7 days or more. We identified 6 such children (male/female: 3/3) aged 3–9 years who were treated between 1998 and 2006. During the same period, 190 children with MP were admitted to our institution. Results Common laboratory findings of the patients included cytopenia, elevated serum lactate dehydrogenase and ferritin levels, and elevated urine β2-microglobulin levels, suggesting complication of hypercytokinemic condition. We initiated intravenous methylprednisolone at a dose of 30mg/kg on 10.2±2.8 clinical days and administered it once daily for 3 consecutive days. Fever subsided 4–14h after initiation of steroid pulse therapy in all patients. This dramatic effect was accompanied by rapid improvement of radiological abnormalities including infiltrates and pleural effusion, followed by improvement of laboratory abnormalities. There were no adverse events of steroid therapy. Conclusions This is the first case-series study showing an effect of 3-day methylprednisolone pulse therapy on refractory MP in children. This therapy is apparently an efficacious and well-tolerated treatment for refractory MP.


title: The avian coronavirus spike protein

text: Abstract Avian coronaviruses of the genus Gammacoronavirus are represented by infectious bronchitis virus (IBV), the coronavirus of chicken. IBV causes a highly contagious disease affecting the respiratory tract and, depending on the strain, other tissues including the reproductive and urogenital tract. The control of IBV in the field is hampered by the many different strains circulating worldwide and the limited protection across strains due to serotype diversity. This diversity is believed to be due to the amino acid variation in the S1 domain of the major viral attachment protein spike. In the last years, much effort has been undertaken to address the role of the avian coronavirus spike protein in the various steps of the virus’ live cycle. Various models have successfully been developed to elucidate the contribution of the spike in binding of the virus to cells, entry of cell culture cells and organ explants, and the in vivo tropism and pathogenesis. This review will give an overview of the literature on avian coronavirus spike proteins with particular focus on our recent studies on binding of recombinant soluble spike protein to chicken tissues. With this, we aim to summarize the current understanding on the avian coronavirus spike's contribution to host and tissue predilections, pathogenesis, as well as its role in therapeutic and protective interventions.


title: MERS: emergence of a novel human coronavirus

text: A novel coronavirus (CoV) that causes a severe lower respiratory tract infection in humans, emerged in the Middle East region in 2012. This virus, named Middle East respiratory syndrome (MERS)-CoV, is phylogenetically related to bat CoVs, but other animal species like dromedary camels may potentially act as intermediate hosts by spreading the virus to humans. Although human to human transmission has been demonstrated, analysis of human MERS clusters indicated that chains of transmission were not self-sustaining, especially when infection control was implemented. Thus, timely identification of new MERS cases followed by their quarantine, combined with measures to limit spread of the virus from the (intermediate) host to humans, may be crucial in controlling the outbreak of this emerging CoV.


title: A multi-target, non-infectious and clonable artificial positive control for routine PCR-based assays

text: Abstract Positive controls are essential for PCR reliability and are challenging to obtain for rare, exotic and/or emerging pathogens and pose biosafety risks if manufactured using infectious pathogens. Custom synthetic DNA inserts can be designed de novo in tandems of forward and reverse complement priming sequences to be inserted in circular plasmid vectors. To test this concept, artificial positive controls (APCs) for use in PCR were synthesized to contain primer sequences targeting four viruses (Barley yellow dwarf virus, Soilborne wheat mosaic virus, Triticum mosaic virus and Wheat streak mosaic virus) pathogenic to wheat and, as internal control, the plant mitochondrial nad5 gene. Thermodynamics and folding parameters of twenty-four APC inserts were assessed in silico. Two thermodynamically different APCs, designated optimal and sub-optimal, were cloned and tested using end point PCR. The optimal APC had a 100% amplification rate, while only 92% of virus-infected plant tissues, commonly used as reference positive controls, amplified. An array of APC priming sequences from different organisms and/or previously tested primers can be accommodated in a large and flexible number of positive control targets. APCs will streamline and standardize routine PCR, improve reliability and biosafety, and create opportunities for development and commercialization of new synthetic positive control sequences.


title: Influenza

text: Summary Although most influenza infections are self-limited, few other diseases exert such a huge toll of suffering and economic loss. Despite the importance of influenza, there had been, until recently, little advance in its control since amantadine was licensed almost 40 years ago. During the past decade, evidence has accrued on the protection afforded by inactivated vaccines and the safety and efficacy in children of live influenza-virus vaccines. There have been many new developments in vaccine technology. Moreover, work on viral neuraminidase has led to the licensing of potent selective antiviral drugs, and economic decision modelling provides further justification for annual vaccination and a framework for the use of neuraminidase inhibitors. Progress has also been made on developing near-patient testing for influenza that may assist individual diagnosis or the recognition of widespread virus circulation, and so optimise clinical management. Despite these advances, the occurrence of avian H5N1, H9N2, and H7N7 influenza in human beings and the rapid global spread of severe acute respiratory syndrome are reminders of our vulnerability to an emerging pandemic. The contrast between recent cases of H5N1 infection, associated with high mortality, and the typically mild, self-limiting nature of human infections with avian H7N7 and H9N2 influenza shows the gaps in our understanding of molecular correlates of pathogenicity and underlines the need for continuing international research into pandemic influenza. Improvements in animal and human surveillance, new approaches to vaccination, and increasing use of vaccines and antiviral drugs to combat annual influenza outbreaks are essential to reduce the global toll of pandemic and interpandemic influenza.


title: SARS-related Perceptions in Hong Kong

text: To understand different aspects of community responses related to severe acute respiratory syndrome (SARS), 2 population-based, random telephone surveys were conducted in June 2003 and January 2004 in Hong Kong. More than 70% of respondents would avoid visiting hospitals or mainland China to avoid contracting SARS. Most respondents believed that SARS could be transmitted through droplets, fomites, sewage, and animals. More than 90% believed that public health measures were efficacious means of prevention; 40.4% believed that SARS would resurge in Hong Kong; and ≈70% would then wear masks in public places. High percentages of respondents felt helpless, horrified, and apprehensive because of SARS. Approximately 16% showed signs of posttraumatic symptoms, and ≈40% perceived increased stress in family or work settings. The general public in Hong Kong has been very vigilant about SARS but needs to be more psychologically prepared to face a resurgence of the epidemic.


title: Fatal multiorgan failure due to yellow fever vaccine-associated viscerotropic disease

text: Yellow fever vaccine-associated viscerotropic disease (YEL-AVD) is a rare complication of yellow fever (YF) vaccination. A previously healthy 22-year-old female died following YF vaccination despite aggressive measures. Serial viral load titers, cytokine levels and host genetic factors were evaluated in an attempt to understand this unusual and lethal outcome. The patient's high-titer vaccine viremia and possibly related minor genetic anomalies provide clues to exploring the etiology of YEL-AVD.


Attributing Priority to Elective Knee Operations/Patients during the re-introduction of Elective Care


title: Applications of Functional Protein Microarrays in Basic and Clinical Research

text: The protein microarray technology provides a versatile platform for characterization of hundreds of thousands of proteins in a highly parallel and high-throughput manner. It is viewed as a new tool that overcomes the limitation of DNA microarrays. On the basis of its application, protein microarrays fall into two major classes: analytical and functional protein microarrays. In addition, tissue or cell lysates can also be directly spotted on a slide to form the so-called “reverse-phase” protein microarray. In the last decade, applications of functional protein microarrays in particular have flourished in studying protein function and construction of networks and pathways. In this chapter, we will review the recent advancements in the protein microarray technology, followed by presenting a series of examples to illustrate the power and versatility of protein microarrays in both basic and clinical research. As a powerful technology platform, it would not be surprising if protein microarrays will become one of the leading technologies in proteomic and diagnostic fields in the next decade.


Coronaviruses as DNA Wannabes: A New Model for the Regulation of RNA Virus Replication Fidelity


title: The Smallpox Epidemics in America in the 1700s and the Role of the Surgeons: Lessons to be Learned During the Global Outbreak of COVID-19

text: Today’s COVID-19 pandemic offers many similarities with previous pandemics hitting our country. In particular, the smallpox epidemics during the 1700s threatened the lives of multitudes and created panic and fear in the society, similar to the situation caused by the coronavirus. Remedies that were instituted, especially inoculations, were met with opposition and even violence when first introduced. The newspapers were filled with headlines reflecting the disputes. There was a “six feet rule” during the smallpox epidemics, although it had a different meaning than today. Politicians and other leaders of the society were engaged in the war against the infection. Boston became involved in the fight against the smallpox by Dr. Zabdiel Boylston’s and Rev. Cotton Mather’s introduction of inoculations. When George Washington realized the benefits of the procedure and ordered mass inoculations of the Continental Army, it became an important factor in winning not only the fight against smallpox but the Revolutionary War as well. Looking back at history, realizing that we have survived previous outbreaks of devastating diseases, can provide hope during the current pandemic.


title: Combining Clinical and Epidemiologic Features for Early Recognition of SARS

text: Early recognition and rapid initiation of infection control precautions are currently the most important strategies for controlling severe acute respiratory syndrome (SARS). No rapid diagnostic tests currently exist that can rule out SARS among patients with febrile respiratory illnesses. Clinical features alone cannot with certainty distinguish SARS from other respiratory illnesses rapidly enough to inform early management decisions. A balanced approach to screening that allows early recognition of SARS without unnecessary isolation of patients with other respiratory illnesses will require clinicians not only to look for suggestive clinical features but also to routinely seek epidemiologic clues suggestive of SARS coronavirus exposure. Key epidemiologic risk factors include 1) exposure to settings where SARS activity is suspected or documented, or 2) in the absence of such exposure, epidemiologic linkage to other persons with pneumonia (i.e., pneumonia clusters), or 3) exposure to healthcare settings. When combined with clinical findings, these epidemiologic features provide a possible strategic framework for early recognition of SARS.