title: Hyperinflammation and derangement of renin-angiotensin-aldosterone system in COVID-19: A novel hypothesis for clinically suspected hypercoagulopathy and microvascular immunothrombosis

text: Abstract Early clinical evidence suggests that severe cases of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are frequently characterized by hyperinflammation, imbalance of renin-angiotensin-aldosterone system, and a particular form of vasculopathy, thrombotic microangiopathy, and intravascular coagulopathy. In this paper, we present an immunothrombosis model of COVID-19. We discuss the underlying pathogenesis and the interaction between multiple systems, resulting in propagation of immunothrombosis, which through investigation in the coming weeks, may lead to both an improved understanding of COVID-19 pathophysiology and identification of innovative and efficient therapeutic targets to reverse the otherwise unfavorable clinical outcome of many of these patients.


Sport in the tracks and fields of the corona virus: critical issues during the exit from lockdown


title: Src inhibitor reduces permeability without disturbing vascularization and prevents bone destruction in steroid-associated osteonecrotic lesions in rabbits

text: To examine the therapeutic effect of Src inhibitor on the VEGF mediating vascular hyperpermeability and bone destruction within steroid-associated osteonecrotic lesions in rabbits. Rabbits with high risk for progress to destructive repair in steroid-associated osteonecrosis were selected according to our published protocol. The selected rabbits were systemically administrated with either Anti-VEGF antibody (Anti-VEGF Group) or Src inhibitor (Src-Inhibition Group) or VEGF (VEGF-Supplement Group) or a combination of VEGF and Src inhibitor (Supplement & Inhibition Group) or control vehicle (Control Group) for 4 weeks. At 0, 2 and 4 weeks after administration, in vivo dynamic MRI, micro-CT based-angiography, histomorphometry and immunoblotting were employed to evaluate the vascular and skeletal events in different groups. The incidence of the destructive repair in the Anti-VEGF Group, Src-Inhibition Group and Supplement & Inhibition Group was all significantly lower than that in the Control Group. The angiogenesis was promoted in VEGF-Supplement Group, Src-Inhibition Group and Supplement & Inhibition Group, while the hyperpermeability was inhibited in Anti-VEGF Group, Src-Inhibition Group and Supplement & Inhibition Group. The trabecular structure was improved in Src-Inhibition Group and Supplement & Inhibition Group. Src inhibitor could reduce permeability without disturbing vascularization and prevent destructive repair in steroid-associated osteonecrosis.


“Urinary Tract Infection” in the Era of COVID‐19


title: Chapter 52 Gerbils

text: The chapter provides an overview of the taxonomy, history, and origin of the Mongolian gerbil. It provides quick, easy-to-use information on anatomy, physiology, and behavior as well as management and husbandry practices. It assists in the humane care and use of gerbils by including details on basic experimental methods for investigators, veterinary care, and the commonly seen diseases. Some more common uses of gerbils in research are described.


title: Respiratory and fecal shedding of Porcine respiratory coronavirus (PRCV) in sentinel weaned pigs and sequence of the partial S-gene of the PRCV isolates

text: Porcine respiratory coronavirus (PRCV), a spike (S) gene deletion mutant of Transmissible gastroenteritis virus (TGEV), causes mild or subclinical respiratory infections in pigs. The shedding of PRCV/TGEV was studied at different days post-arrival in fecal and nasal swabs from PRCV/TGEV seronegative sentinel pigs introduced into a PRCV seropositive herd with questionable TGEV serology and diarrhea. Nasal shedding of PRCV was detected in 57% and 63% of samples by nested-RT-PCR and cell culture immunofluorescence (CCIF), respectively. However fecal shedding of PRCV was detected in 37% of the samples by nested-RT-PCR and 19% by CCIF. Four respiratory and 5 fecal PRCV strains were isolated in swine testicle cells including nasal/fecal PRCV pairs (isolated at the same time) from 3 pigs. Comparison of nasal/fecal PRCV pairs from individual pigs revealed different deletions in the spike (S) gene (648 or 681 nt) in 2 pairs and a consistent change in nt 790/791 (aa T to V) for all pairs. In preliminary studies, inoculation of gnotobiotic pigs with each plaque-purified pair of the nasal and fecal PRCV isolates, revealed no clinical disease but different tropisms. The nasal isolate was shed both nasally and in feces, but the fecal isolate was shed only marginally in feces, and not nasally. Our results show that nested-RT-PCR was as sensitive as CCIF for PRCV detection in nasal swabs, but was more sensitive than CCIF for PRCV detection in fecal samples; alternatively PRCV shed in feces was more labile with loss of infectivity. The S-gene sequence differences found between the fecal and respiratory PRCV isolates may influence their tissue tropism. These new PRCV isolates should be useful to understand the molecular basis of coronavirus tropism and evolution in infected swine.


title: PrEP-001 prophylactic effect against rhinovirus and influenza virus - RESULTS of 2 randomized trials

text: Abstract BACKGROUND PrEP-001 Nasal Powder, a proprietary formulation of polyriboinosinic and polyribocytidylic acid effectively elicits a cellular innate immune response in nasal epithelium. The aim of these 2 studies was to investigate the safety and efficacy of PrEP-001 prophylaxis against rhinovirus (HRV-A16) and influenza-A (H3N2-IAV). METHODS Healthy subjects randomly received 2 doses of PrEP-001 or placebo, 48 and 24 h pre-challenge with 10 TCID50 of HRV-A16 (Study 1) or H3N2-IAV (Study 2). RESULTS In Study 1, PrEP-001 reduced median total symptom score from 38.5 to 4.5 (p = 0.004), median symptom duration from 6.0 to 1.7 days and median mucus production from 15 g to 3 g. The percentage of subjects classified as ill was reduced 3-fold (placebo 73%, PrEP-001 23%, p = 0.002). In Study 2, PrEP-001 reduced median total symptom score from 8.0 to 4.1 (p = 0.021), median symptom duration from 4.6 to 3.7 days and median mucus production from 3.6 g to 1.5 g. The percentage of subjects classified as ill was reduced 2-fold (placebo 48%, PrEP-001 24%, p = 0.064). PrEP-001 reduced peak viral shedding in both studies, as assessed by qRT-PCR of nasal lavage. Seroconversion rates were comparable between placebo and PrEP-001 (Study 1: 77% [both arms]; Study 2: placebo 73%, PrEP-001 80%). PrEP-001 was well-tolerated, with no clinically significant adverse events. CONCLUSIONS PrEP-001 reduced the number of individuals with clinical illness and attenuated severity and duration of HRV-A16 and H3N2-IAV infections without compromising seroconversion, and was well-tolerated. This supports further evaluation of PrEP-001 as a potential pan-viral prophylaxis for upper respiratory tract infections. CLINICAL TRIAL REGISTRATION Study 1, HRV-A16 study: EudraCT Number 2012-005579-14 (study conducted before ClinicalTrials.gov registration required). Study 2, H3N2-IAV study: EudraCT Number 2015-002895-26 and ClinicalTrials.gov: NCT03220048.


title: Molecular detection and typing of human picornaviruses

text: Abstract Picornaviruses include several important clinical pathogens which cause diseases varying from common cold to poliomyelitis and hepatitis. Introduction of RT-PCR methods for the detection of these viruses has significantly facilitated the diagnosis of picornavirus infections and elucidated their etiological role in clinical illnesses. Partial sequence analysis of the genomes has been used for typing of the viruses and in studies of molecular epidemiology of picornaviruses. These molecular approaches are likely to become the most predominant techniques for the diagnosis and epidemiological analysis, particularly in the enterovirus infections.


Evaluation of Risks and Benefits Associated with Vaccination against Coronavirus Infections in Cats


title: Yeast for virus research

text: Budding yeast (Saccharomyces cerevisiae) and fission yeast (Schizosaccharomyces pombe) are two popular model organisms for virus research. They are natural hosts for viruses as they carry their own indigenous viruses. Both yeasts have been used for studies of plant, animal and human viruses. Many positive sense (+) RNA viruses and some DNA viruses replicate with various levels in yeasts, thus allowing study of those viral activities during viral life cycle. Yeasts are single cell eukaryotic organisms. Hence, many of the fundamental cellular functions such as cell cycle regulation or programed cell death are highly conserved from yeasts to higher eukaryotes. Therefore, they are particularly suited to study the impact of those viral activities on related cellular activities during virus-host interactions. Yeasts present many unique advantages in virus research over high eukaryotes. Yeast cells are easy to maintain in the laboratory with relative short doubling time. They are non-biohazardous, genetically amendable with small genomes that permit genome-wide analysis of virologic and cellular functions. In this review, similarities and differences of these two yeasts are described. Studies of virologic activities such as viral translation, viral replication and genome-wide study of virus-cell interactions in yeasts are highlighted. Impacts of viral proteins on basic cellular functions such as cell cycle regulation and programed cell death are discussed. Potential applications of using yeasts as hosts to carry out functional analysis of small viral genome and to develop high throughput drug screening platform for the discovery of antiviral drugs are presented.


title: Discovery and Partial Genomic Characterisation of a Novel Nidovirus Associated with Respiratory Disease in Wild Shingleback Lizards (Tiliqua rugosa)

text: A respiratory disease syndrome has been observed in large numbers of wild shingleback lizards (Tiliqua rugosa) admitted to wildlife care facilities in the Perth metropolitan region of Western Australia. Mortality rates are reportedly high without supportive treatment and care. Here we used next generation sequencing techniques to screen affected and unaffected individuals admitted to Kanyana Wildlife Rehabilitation Centre in Perth between April and December 2015, with the resultant discovery of a novel nidovirus significantly associated with cases of respiratory disease according to a case definition based on clinical signs. Interestingly this virus was also found in 12% of apparently healthy individuals, which may reflect testing during the incubation period or a carrier status, or it may be that this agent is not causative in the disease process. This is the first report of a nidovirus in lizards globally. In addition to detection of this virus, characterisation of a 23,832 nt segment of the viral genome revealed the presence of characteristic nidoviral genomic elements providing phylogenetic support for the inclusion of this virus in a novel genus alongside Ball Python nidovirus, within the Torovirinae sub-family of the Coronaviridae. This study highlights the importance of next generation sequencing technologies to detect and describe emerging infectious diseases in wildlife species, as well as the importance of rehabilitation centres to enhance early detection mechanisms through passive and targeted health surveillance. Further development of diagnostic tools from these findings will aid in detection and control of this agent across Australia, and potentially in wild lizard populations globally.


title: Public Health Emergency and Crisis Management: Case Study of SARS-CoV-2 Outbreak

text: The SARS-CoV-2 pandemic has caused an unparalleled public health crisis, delivering an immense shock to humanity. With the virus’s health consequences largely unknown, different health systems around the globe have pursued various avenues of crisis management. South Korea, troubled early by the virus, was once the second most affected nation in the world. Arrays of measures in South Korea, such as large-scale diagnostic testing and technology-based comprehensive contact tracing, have brought about debates among public health experts and medical professionals. This case study describes the major cluster transmissions in SARS-CoV-2 hotspots in South Korea (such as a religious sect, a call center, logistics facilities, and nightclubs) and offers early observations on how South Korean public health authorities acted in response to the initial outbreak of the virus and to the new waves prompted by re-opening economies. We then discuss the way in which South Korea’s experience can act as a reference for shaping other countries’ public health strategies in pandemic crisis management.


title: Laboratory biosafety in China: past, present, and future

text: Abstract The launch of the new journal, Biosafety and Health, presents me with a unique opportunity to recount the progress of laboratory biosafety (LB) in China and my contribution to this area over the past 30 years. Since the severe acute respiratory syndrome epidemic in 2003, China has constructed a primary network of high-level biosafety laboratories at different levels and established an expert team on LB. Furthermore, a series of LB management documents, including laws, regulations, standards, and guidelines, have been developed and published. This gradually maturing LB system has played a pivotal role in emerging infectious disease control and prevention, as well as in research, which in turn contributes to public health. In recent years, international collaboration between China and other countries has also been accelerated. Despite these achievements, we are still facing many challenges and opportunities in the field of LB. Sustainable LB development requires the joint efforts of the entire society and continuous international cooperation to safeguard global public health.


title: Effect of isolation practice on the transmission of middle east respiratory syndrome coronavirus among hemodialysis patients: A 2-year prospective cohort study

text: Hemodialysis (HD) patients had a high rate of infection transmission and mortality during the middle east respiratory syndrome coronavirus (MERS-CoV) outbreak in Saudi Arabia. A standardized guideline on isolation technique for exposed HD patients is not available. Thus, this study aimed to evaluate the effect of different isolation strategies on the prevention of secondary viral transmission and clinical outcomes among exposed HD patients. During the 2015 MERS-CoV outbreak in Korea, 116 patients in 3 HD units were incidentally exposed to individuals with confirmed MERS-CoV infection and underwent different types of isolation, which were as follows: single-room isolation (n = 54, 47%), cohort isolation (n = 46, 40%), and self-imposed quarantine (n = 16, 13%). The primary outcome was rate of secondary viral transmission. The secondary outcome measures were changes in clinical and biochemical markers during the isolation period, difference in clinical and biochemical markers according to the types of isolation practice, and effect of isolation practice on patient survival. During a mean isolation period of 15 days, no further cases of secondary transmission were detected among HD patients. Plasma hemoglobin, serum calcium, and serum albumin levels and single-pool Kt/V decreased during the isolation period but normalized thereafter. Patients who were subjected to self-imposed quarantine had higher systolic and diastolic blood pressure, lower total cholesterol level, and lower Kt/V than those who underwent single-room or cohort isolation. During the 24-month follow-up period, 12 patients died. However, none of the deaths occurred during the isolation period, and no differences were observed in patient survival rate according to different isolation strategies. Although 116 participants in 3 HD units were incidentally exposed to MERS-CoV during the 2015 outbreak in Korea, strict patient surveillance and proper isolation practice prevented secondary transmission of the virus. Thus, a renal disaster protocol, which includes proper contact surveillance and isolation practice, must be established in the future to accommodate the needs of HD patients during disasters or outbreaks.


title: COVID-19: Role of Ambulatory Surgery Facilities in This Global Pandemic

text: Coronavirus Disease 2019 (COVID-19) has now become a global pandemic. This has led the United States to declare a national emergency and resulted in a ban on all elective diagnostic and therapeutic procedures as well as elective surgery in inpatient and outpatient settings. Ambulatory surgery facilities (ASF) that perform only elective procedures are thus likely to be closed. However, these facilities may be able to assist acute care hospitals as essential (urgent and emergent) surgeries and diagnostic and therapeutic procedures will still need to be performed. The aim of this article is to explore the potential contribution of ASFs in the current health care crisis. It is important to understand that COVID-19–related information is continually evolving, and thus, the discussion provided here is subject to change.


title: MERS-CoV spike nanoparticles protect mice from MERS-CoV infection

text: The Middle East respiratory syndrome coronavirus (MERS-CoV) was first discovered in late 2012 and has gone on to cause over 1800 infections and 650 deaths. There are currently no approved therapeutics or vaccinations for MERS-CoV. The MERS-CoV spike (S) protein is responsible for receptor binding and virion entry to cells, is immunodominant and induces neutralizing antibodies in vivo, all of which, make the S protein an ideal target for anti-MERS-CoV vaccines. In this study, we demonstrate protection induced by vaccination with a recombinant MERS-CoV S nanoparticle vaccine and Matrix-M1 adjuvant combination in mice. The MERS-CoV S nanoparticle vaccine produced high titer anti-S neutralizing antibody and protected mice from MERS-CoV infection in vivo.


Emergence of MERS-CoV in the Middle East: Origins, Transmission, Treatment, and Perspectives


title: China's distinctive engagement in global health

text: China has made rapid progress in four key domains of global health. China's health aid deploys medical teams, constructs facilities, donates drugs and equipment, trains personnel, and supports malaria control mainly in Africa and Asia. Prompted by the severe acute respiratory syndrome (SARS) outbreak in 2003, China has prioritised the control of cross-border transmission of infectious diseases and other health-related risks. In governance, China has joined UN and related international bodies and has begun to contribute to pooled multilateral funds. China is both a knowledge producer and sharer, offering lessons based on its health accomplishments, traditional Chinese medicine, and research and development investment in drug discovery. Global health capacity is being developed in medical universities in China, which also train foreign medical students. China's approach to global health is distinctive; different from other countries; and based on its unique history, comparative strength, and policies driven by several governmental ministries. The scope and depth of China's global engagement are likely to grow and reshape the contours of global health.


title: Bibliometric analysis of pathogenic organisms

text: Abstract Infectious diseases remain as an important public health threat to humans. Research into pathogens can be useful for planning an organized response to infectious diseases. Bibliometric analysis is an important method for scientific research and assessing capability. In this study, 100 pathogens of public health importance were selected, and the distributions of annual, national, institutional, and journal publications were statistically analyzed. The United States of America ranked the first in terms of the number of relevant studies published. China attaches great importance to the prevention and control of infectious diseases, but still needs to improve in the following areas: for example, insufficient Science Citation Index reports on particular pathogens, institutions SCI reports on pathogens lower than world top pathogen research institutions, and lack of influential international pathogen-related journals. Scientific literature databases are important tools for science-of-science analysis. The findings of this study shed light on the hot spots and the ignored spots in pathogen researches, and thus would be useful for drawing a national and institutional research plan.


title: Could BCG be used to protect against COVID-19?

text: Nearly 100 years since it was first used in humans as a vaccine for tuberculosis, Bacillus Calmette–Guérin (BCG) has been suggested as a possible agent to prevent coronavirus disease 2019 (COVID-19). A number of studies are underway to investigate this possibility but — even if they prove effective — many questions will remain.


title: Tourism and glocalization “Local” Tour Guiding

text: Abstract In tourism studies globalization and localization are often conceived of as a binary opposition. The ethnography of an Indonesian group of tour guides presented here illustrates how the global and the local are intimately intertwined through what has been described as the process of “glocalization”. The guides studied are remarkable front-runners of glocalization. They fully participate in global popular culture and use new technologies in their private lives. While guiding, however, they skillfully represent the glocalized life around them as a distinctive “local”, adapted to the tastes of different groups of international tourists. It is concluded that tourism offers excellent opportunities to study glocalization, but that more grounded research is needed.


title: Health care workers' views about respirator use and features that should be included in the next generation of respirators

text: BACKGROUND: Numerous studies have demonstrated that health care workers are, in general, poorly compliant with respiratory protection guidelines, especially when a N95 respirator is recommended. The purpose of this study was to assess health care workers' views about respirator use and the features they prefer to be included in the next generation of respirators. METHODS: A 63-item survey was distributed to health care workers in 27 units of 2 tertiary care medical centers. RESULTS: From a total of 559 surveys distributed at both hospitals, 159 responses were returned (response rate, 28%). Survey results indicated that health care workers seek respirators that are more comfortable, interfere less with breathing, diminish heat buildup, are disposable, and permit the user to have facial hair. Multivariate analyses suggest that emergency department staff had 12.3 greater odds of wanting a new respirator (P = .031) as compared with their referent group. Males were more likely to indicate that the N95 respirator was comfortable to wear versus females (P = .003). CONCLUSION: To increase substantially the acceptance of respiratory protective equipment and improve compliance rates, respirators should be modified to meet the specific needs of health care workers.


title: Vaccines: past, present and future

text: The vaccines developed over the first two hundred years since Jenner's lifetime have accomplished striking reductions of infection and disease wherever applied. Pasteur's early approaches to vaccine development, attenuation and inactivation, are even now the two poles of vaccine technology. Today, purification of microbial elements, genetic engineering and improved knowledge of immune protection allow direct creation of attenuated mutants, expression of vaccine proteins in live vectors, purification and even synthesis of microbial antigens, and induction of a variety of immune responses through manipulation of DNA, RNA, proteins and polysaccharides. Both noninfectious and infectious diseases are now within the realm of vaccinology. The profusion of new vaccines enables new populations to be targeted for vaccination, and requires the development of routes of administration additional to injection. With all this come new problems in the production, regulation and distribution of vaccines.


title: Genomic and subgenomic RNAs of rabbit hemorrhagic disease virus are both protein-linked and packaged into particles

text: Abstract The major subgenomic RNA of the calicivirus rabbit hemorrhagic disease virus which codes for the viral capsid protein has been cloned as cDNA. The nucleotide sequence of this mRNA was shown to be identical to the 3′ terminal region of the genomic RNA. The 5′ end of the mRNA corresponds to position 5296 of the genomic sequence; except for two differences the first 16 nucleotides of genomic and subgenomic RNAs are identical. After isolation from liver tissue viral genomic and subgenomic RNAs were found to be resistant to RNase degradation. This protection was due to RNA packaging into particles. Sucrose density gradient centrifugation of liver homogenates allowed separation of such particles containing either genomic RNA or subgenomic RNA. Genomic and subgenomic RNAs are protein-linked and for the genomic molecule this interaction is localized within the first 179 nucleotides. After radioactive labeling of purified RNA and subsequent RNase treatment a protein of 15 kDa was identified.


Cardiac magnetic resonance characterization of COVID-19 myocarditis


title: Lessons from China When Performing Neurosurgical Procedures During the Coronavirus Disease 2019 (COVID-19) Pandemic

text: The novel coronavirus disease 2019 (COVID-19) pandemic poses a substantial threat to the health of health care personnel on the front line of caring for patients with COVID-19. The Centers for Medicare and Medicaid Services have announced that all nonessential planned surgeries and procedures should be postponed until further notice and only urgent procedures should proceed. Neurologic surgeries and procedures should not be delayed under the circumstance in which it is essential at saving a life or preserving functioning of the central nervous system. With the intent to advise the neurosurgery team on how to adequately prepare and safely perform neurosurgical procedures on confirmed and suspected patients with COVID-19, we discuss considerations and recommendations based on the lessons and experience shared by neurosurgeons in China. Perioperative and intraoperative strategies, considerations, as well as challenges arisen under the specific circumstance have been discussed. In addition, a case of a ruptured aneurysm in a suspected patient with COVID-19 is reported. It is advised that all health care personnel who immediately participate in neurosurgical surgeries and procedures for confirmed and suspected patients with COVID-19 should take airborne precautions and wear enhanced personal protective equipment. Following the proposed guidance, urgent neurosurgical surgeries and procedures can be safely performed for the benefit of critical patients with or suspected for COVID-19.


title: A fine balance: Immunosuppression and immunotherapy in a patient with multiple sclerosis and COVID-19

text: Abstract Background : Treatment decisions in patients with multiple sclerosis (MS) during the coronavirus disease 2019 (COVID-19) pandemic are challenging. It is not known whether and how various disease modifying therapies, especially immunosuppressive drugs, affect COVID-19 risk and disease course. Methods : Case report Results : We report a fingolimod-treated MS patient who developed severe COVID-19 but recovered after treatment with tocilizumab. Conclusion : This report suggests that a brief course of tocilizumab for the treatment of severe COVID-19 may be effective while not aggravating pre-existing MS.


title: Characteristic features and outcomes of severe acute respiratory syndrome found in severe acute respiratory syndrome intensive care unit patients

text: Abstract Purpose The aim of the study was to identify characteristic clinical features and outcomes of critically ill patients with confirmed severe acute respiratory syndrome (SARS). Materials and Methods This retrospective study enrolled all patients admitted to a 12-bed SARS intensive care unit (ICU) in a tertiary care medical center in Taipei between May 15 and July 17, 2003. Patients with positive results of either reverse transcriptase–polymerase chain reaction or antibody to SARS coronavirus were defined as SARS cases and others with negative results as control cases. Results Of the 50 patients, 14 had confirmed SARS. Demographics were similar between the 2 groups. The highest leukocyte and neutrophil counts, lactate dehydrogenase, and creatine kinase; positive end-expiratory pressure; and use of corticosteroids, ribavirin, and intravenous immunoglobulin were higher in the SARS group. In contrast, the lowest lymphocyte count and the ratio of Pao 2 to the fraction of inspired oxygen were lower in the SARS group. Of the 15 deaths in the control group, 12 (80%) occurred during the first 2 weeks after ICU admission. However, in the confirmed SARS group, 5 (55.6%) of the 9 deaths occurred within the third or fourth week. This difference in timing between these 2 groups was significant (P = .004). Conclusions In a SARS ICU, patients with a confirmed diagnosis of SARS had significantly different clinical features and timing of mortality from those of the control group.


title: Quarantine, isolation and the duty of easy rescue in public health

text: We address the issue of whether, why and under what conditions, quarantine and isolation are morally justified, with a particular focus on measures implemented in the developing world. We argue that the benefits of quarantine and isolation justify some level of coercion or compulsion by the state, but that the state should be able to provide the strongest justification possible for implementing such measures. While a constrained form of consequentialism might provide a justification for such public health interventions, we argue that a stronger justification is provided by a principle of State Enforced Easy Rescue: a state may permissibly compel individuals to engage in activities that entail a small cost to them but a large benefit to others, because individuals have a moral duty of easy rescue to engage in those activities. The principle of State Enforced Easy Rescue gives rise to an Obligation Enforcement Requirement: the state should create the conditions such that submitting to coercive or compulsive measures becomes a fundamental moral duty of individuals, i.e. a duty of easy rescue. When the state can create such conditions, it has the strongest justification possible for implementing coercive or compulsive measures, because individuals have a moral duty to temporarily relinquish the rights that such measures would infringe. Our argument has significant implications for how public health emergencies in the developing world should be tackled. Where isolation and quarantine measures are necessary, states or the international community have a moral obligation to provide certain benefits to those quarantined or isolated.


title: Detection of non-primate hepaciviruses in UK dogs

text: Abstract Non-primate hepacivirus (NPHV) has been identified in dogs, horses, bats and wild rodents. The presence of NPHV in dogs outside of the USA however is yet to be established. Here we describe for the first time the detection of NPHV in the UK dog population (described throughout the manuscript as CnNPHV). We examined tissues collected from dogs housed in a rehoming kennel where respiratory disease was endemic. CnNPHV RNA was detected in the tracheal tissues of 48/210 dogs by RT-PCR, and in the liver, lung and/or tracheal tissues of 12/20 dogs. The presence of CnNPHV RNA, and its tropism was confirmed by in situ hybridisation. Histopathological examination demonstrated a trend toward higher histopathological scores in CnNPHV RNA positive respiratory tissues, although, this was not statistically significant. Our findings broaden the geographic distribution and our understanding of CnNPHV. Further evidence of CnNPHV replication in canids warrants investigation.


title: Methylene blue covalently attached to single stranded DNA as electroactive label for potential bioassays

text: Abstract Methylene blue is an electroactive molecule that has been employed for the detection of the DNA hybridization event in electrochemical sensors. However, its use as a covalent label is very scarce and in most of the cases, non-covalent interactions (hydrophobic, electrostatic) are employed. Although it has advantages as simplicity and fewer number of procedure steps, the covalent attachment is less exploited in the development of these sensors. In this article, the electrochemical behavior of methylene blue attached to different DNA-strands is studied. Several lengths (15- and 30-mer) and different degree of DNA modification (MB-DNA, MB-DNA-MB and MB-DNA-SH) have been studied. The highest signals were obtained for longer strands with two MB molecules. In all the cases the signal is enhanced by CNT-nanostructuration of the electrode. Adsorption on these modified screen-printed electrodes allowed the amplification by employing an accumulation time. In this way, a sensitivity of −0.2864μAμM−1 and a limit of detection of 800nM for a 120s accumulation time were obtained.


title: Infectiologie itinérante

text: Résumé Objectifs Une prise de conscience s’impose à l’égard du développement actuel des épidémies d’infections sévères. Le développement considérable des transports internationaux a beaucoup amplifié la circulation des agents infectieux, véhiculés par les voyageurs et les migrants, mais aussi par les animaux et les marchandises. Observations La distribution des infections à potentiel épidémique, dont certaines maladies émergentes, a tendance à devenir planétaire. Cette évolution impose un renforcement de la surveillance internationale et des capacités de réponse aux alertes. Solutions Les pays industrialisés, les mieux équipés en moyens et en structures opérationnelles, interviennent de façon prépondérante dans cette lutte. Leur contribution est nécessaire dans les pays en développement, particulièrement affectés par les endémo-épidémies infectieuses, et cette contribution progresse et doit être soutenue. Cette revue rapporte à travers des observations personnelles les pathologies les plus menaçantes à travers le monde. Abstract Objectives We have to become aware of the current development of international travels which has contributed to amplify circulation of all sorts of infectious agents. We will describe the current situation. Observations Infectious agents are carried by means of travellers, immigrants, as well as by animals, goods and merchandise. The distribution of infections potentially responsible for epidemics tends to become worldwide and some of them are emergent diseases. Solutions Such a situation imposes enhancement of international surveillance and development of resources for control and response to alerts. Developed countries possess most advanced equipments and interventional structures: they are those which may intervene predominantly in the fight against epidemics. The necessary contribution of these industrialized countries is increasing in developing countries in which infectious epidemics are spreading and such intervention must be sustained. The content of the article is a review of major threatening infectious epidemic diseases with the contribution of personal experiences.


title: Expression profile analysis of 5-day-old neonatal piglets infected with porcine Deltacoronavirus

text: BACKGROUND: Porcine deltacoronavirus (PDCoV) is a novel coronavirus that can cause diarrhea in nursing piglets. This study was aimed to investigate the roles of host differentially expressed genes on metabolic pathways in PDCoV infections. RESULTS: Twenty thousand six hundred seventy-four differentially expressed mRNAs were identified in 5-day-old piglets responded to PDCoV experimental infections. Many of these genes were correlated to the basic metabolism, such as the peroxisome proliferator-activated receptor (PPAR) signaling pathway which plays a critical role in digestion. At the same time, in the PPAR pathway genes of fatty acid-binding protein (FABP) family members were observed with remarkably differential expressions. The differential expressed genes were associated with appetite decrease and weight loss of PDCoV- affected piglets. DISCUSSION: Fatty acid-binding protein 1 (FABP1) and fatty acid-binding protein 3 (FABP3) were found to be regulated by PDCoV. These two genes not only mediate fatty acid transportation to different cell organelles such as mitochondria, peroxisome, endoplasmic reticulum and nucleus, but also modulate fatty acid metabolism and storage as a signaling molecule outside the cell. Therefore, it can be preliminarily concluded that PPAR differential expression caused by PDCoV was mostly associated with weight loss and death from emaciation. CONCLUSIONS: The host differentially expressed genes were associated with infection response, metabolism signaling and organismal systems signaling pathways. The genes of FABP family members in the PPAR signaling pathway were the most highly altered and played important roles in metabolism. Alteration of these genes were most likely the reason of weight loss and other clinical symptoms. Our results provided new insights into the metabolic mechanisms and pathogenesis of PDCoV infection. METHODS: Animal experiment, Determination of viral growth by real-time RT-PCR, Histopathology, Immunohistochemical staining, Microarray analysis.


title: The attribute reductions of three-way concept lattices

text: Abstract Three-way concept analysis is a newly proposed area of formal concept analysis from which one can obtain both the inclusion decision and the exclusion decision. In general, given a context, some attributes may not be essential in three-way concept analysis, such as forming three-way concept lattice. So in this paper, we study the attribute reductions of three-way concept lattices in order to make the data easily be understood. Firstly, based on different criteria generated from object-induced three-way concept (OE-concept), four kinds of attribute reductions are proposed. The four reductions together embody different characteristics of a formal context and can be used in different occasions. Secondly, we discuss their relationships, including their advantages and disadvantages and the relationships among consistent sets and among the cores. Thirdly, based on attribute-induced three-way concept (AE-concept), we also give four attribute-induced three-way attribute reductions and discuss their relationships. Finally, the approaches to computing these attribute reductions are presented and the obtained results are demonstrated and verified by an empirical case. In this paper, we systematically investigate the attribute reductions of three-way concept lattices which enriches the study of formal concept analysis.


title: Fish TRIM8 exerts antiviral roles through regulation of the proinflammatory factors and interferon signaling

text: Abstract The tripartite motif (TRIM)-containing proteins usually exert important regulatory roles during multiple biological processes. TRIM8 has been demonstrated to be a RING domain-containing E3 ubiquitin ligase which plays critical roles in inflammation and cancer. In this study, a TRIM8 homolog from grouper, Epinephelus coioides (EcTRIM8) was cloned, and its effects on fish virus replication were investigated. The full-length EcTRIM8 cDNA encoded a polypeptide of 568 amino acids with 92% identity to TRIM8 homolog from large yellow croaker (Larimichthys crocea). Sequence alignment analysis indicated that EcTRIM8 contained conserved RING finger, B-box and coiled-coil domain. Expression patterns analysis showed that EcTRIM8 was predominant in kidney, gill, fin, liver, spleen and brain. After challenging with Singapore grouper iridovirus (SGIV) or polyinosin-polycytidylic acid (poly I:C), the EcTRIM8 transcript was significantly increased at the early stage of injection. Under fluorescence microscopy, we observed different distribution patterns of EcTRIM8 in grouper spleen (GS) cells, including punctate fluorescence evenly situated throughout the cytoplasm and bright aggregates. The ectopic expression of EcTRIM8 in vitro significantly inhibited the replication of SGIV and red spotted grouper nervous necrosis virus (RGNNV), evidenced by the obvious reduction in the severity of cytopathic effect (CPE) and the significant decrease in viral gene transcription and protein synthesis. Moreover, the transcription of the proinflammatory factors and interferon related immune factors were differently regulated by EcTRIM8 during SGIV or RGNNV infection. In addition, overexpression of EcTRIM8 significantly increased the transcription of interferon regulator factor 3 (IRF3) and IRF7, and enhanced IRF3 or IRF7 induced interferon-stimulated response element (ISRE) promoter activity. Together, our results firstly demonstrated that fish TRIM8 could exert antiviral function through the regulation of the expression of proinflammatory cytokines and interferon related transcription factors in response to fish viruses.


title: Unravelling the networks dictating host resistance versus tolerance during pulmonary infections

text: The appearance of single cell microorganisms on earth dates back to more than 3.5 billion years ago, ultimately leading to the development of multicellular organisms approximately 3 billion years later. The evolutionary burst of species diversity and the “struggle for existence”, as proposed by Darwin, generated a complex host defense system. Host survival during infection in vital organs, such as the lung, requires a delicate balance between host defense, which is essential for the detection and elimination of pathogens and host tolerance, which is critical for minimizing collateral tissue damage. Whereas the cellular and molecular mechanisms of host defense against many invading pathogens have been extensively studied, our understanding of host tolerance as a key mechanism in maintaining host fitness is extremely limited. This may also explain why current therapeutic and preventive approaches targeting only host defense mechanisms have failed to provide full protection against severe infectious diseases, including pulmonary influenza virus and Mycobacterium tuberculosis infections. In this review, we aim to outline various host strategies of resistance and tolerance for effective protection against acute or chronic pulmonary infections.


COVID 19: SINDROME FEBRIL Y CLÍNICA NEURÓLOGICA EN NEONATO


Editorial ‐ Nutritional Status Affects COVID‐19 Patient Outcomes


title: Computational screening of antagonist against the SARS-CoV-2 (COVID-19) coronavirus by molecular docking

text: Abstract In the current episode of novel coronavirus (SARS-CoV-2) spreads, antiviral drug discovery is of great importance. Auto dock vina was used to screen potential drugs by molecular docking with the structure protein and non-structure protein sites of new coronavirus. Ribavirin, a common antiviral drug, as well as remdesivir, chloroquine and luteolin, were all studied. Honeysuckle is generally believed to have antiviral effect in traditional Chinese medicine, the main flavonoid in which is Luteolin. In the study, it was found luteolin could bind to the same sites of main protease of SARS-CoV-2 as the control molecular with a high affinity. Chloroquine, was proved clinically effective, can bind to the main protease, which may be the possible antiviral mechanism. And the study was restricted to molecular docking without validation by MD simulations. Interactions with the main protease may play a key role in in fighting against viruses. Luteolin is a potential antiviral molecule worthy of attention.


Methotrexate based oral chemotherapy for advanced oral cancer during COVID-19 pandemic: another option in the therapeutic armamentarium


title: Studies of enteric coronaviruses in a feline cell line

text: Abstract Development is reported of a feline cell line which can support the growth of coronaviruses from canine (CCV), feline (FIPV) and porcine (TGEV) species. The cell culture has been serially transferred over 100 times and has retained its initial growth requirements, proliferative capacity and morphologic features. Each virus had specific growth characteristics in this cell culture although all produced a similar CPE and plaques under agar. Cross neutralization studies demonstrated a two-way relationship between TGEV and CCV and between TGEV and FIPV, whereas a one-way relationship was demonstrated between CCV and FIPV.


title: Chapter 5 Lyssaviruses—Current Trends

text: Abstract Various technological developments have revitalized the approaches employed to study the disease of rabies. In particular, reverse genetics has facilitated the generation of novel viruses used to improve our understanding of the fundamental aspects of rabies virus (RABV) biology and pathogenicity and yielded novel constructs potentially useful as vaccines against rabies and other diseases. Other techniques such as high throughput methods to examine the impact of rabies virus infection on host cell gene expression and two hybrid systems to explore detailed protein–protein interactions also contribute substantially to our understanding of virus–host interactions. This review summarizes much of the increased knowledge about rabies that has resulted from such studies but acknowledges that this is still insufficient to allow rational attempts at curing those who present with clinical disease.


title: Temporal regulation of bovine coronavirus RNA synthesis

text: Abstract The structure and synthesis of bovine coronavirus (BCV)-specific intracellular RNA were studied. A genome-size RNA and seven subgenomic RNAs with molecular weights of approximately 3.3 × 106, 3.1 × 106, 2.6 × 106, 1.1 × 106, 1.0 × 106, 0.8 × 106 and 0.6 × 106 were detected. Comparisons of BCV intracellular RNAs with those of mouse hepatitis virus (MHV) demonstrated the presence of an additional RNA for BCV, species 2a, of 3.1 × 106 daltons. BCV RNAs contain a nested-set structure similar to that of other coronaviruses. This nested-set structure would suggest that the new RNA has a capacity to encode a protein of approximately 430 amino acids. Kinetic studies demonstrated that the synthesis of subgenomic mRNAs and genomic RNA are differentially regulated. At 4 to 8 h post-infection (p.i.), subgenomic RNAs are synthesized at a maximal rate and represent greater than 90% of the total viral RNA synthesized, whereas genome-size RNA accounts for only 7%. Later in infection, at 70 to 72 h p.i., genome-size RNA is much more abundant and accounts for 88% of total RNA synthesized. Immunoprecipitations of [35S]methionine-pulse-labeled viral proteins demonstrated that viral protein synthesis occurs early in the infection, concurrent with the peak of viral subgenomic RNA synthesis. Western blot analysis suggests that these proteins are stable since the proteins are present at high level as late as 70 to 72 h p.i. The kinetics of production of virus particles coincides with the synthesis of genomic RNA. These studies thus indicate that there is a differential temporal regulation of the synthesis of genomic RNA and subgenomic mRNAs, and that the synthesis of genomic RNA is the rate-limiting step regulating the production of virus particles.


title: A Simplified Positive-Sense-RNA Virus Construction Approach That Enhances Analysis Throughput

text: Here we present an approach that advances the throughput of a genetic analysis of a positive-sense RNA virus by simplifying virus construction. It enabled comprehensive dissection of a complex, multigene phenotype through rapid derivation of a large number of chimeric viruses and construction of a mutant library directly from a virus pool. The versatility of the approach described here expands the applicability of diverse genetic approaches to study these viruses.


title: S-layers: principles and applications

text: Monomolecular arrays of protein or glycoprotein subunits forming surface layers (S-layers) are one of the most commonly observed prokaryotic cell envelope components. S-layers are generally the most abundantly expressed proteins, have been observed in species of nearly every taxonomical group of walled bacteria, and represent an almost universal feature of archaeal envelopes. The isoporous lattices completely covering the cell surface provide organisms with various selection advantages including functioning as protective coats, molecular sieves and ion traps, as structures involved in surface recognition and cell adhesion, and as antifouling layers. S-layers are also identified to contribute to virulence when present as a structural component of pathogens. In Archaea, most of which possess S-layers as exclusive wall component, they are involved in determining cell shape and cell division. Studies on structure, chemistry, genetics, assembly, function, and evolutionary relationship of S-layers revealed considerable application potential in (nano)biotechnology, biomimetics, biomedicine, and synthetic biology.


title: Delivery of hepato-pancreato-biliary surgery during the COVID-19 pandemic: an European-African Hepato-Pancreato-Biliary Association (E-AHPBA) cross-sectional survey

text: INTRODUCTION: The extent of the COVID-19 pandemic and the resulting response has varied globally. The European and African Hepato-Pancreato-Biliary Association (E-AHPBA), the premier representative body for practicing HPB surgeons in Europe and Africa, conducted this survey to assess the impact of COVID-19 on HPB surgery. METHODS: An online survey was disseminated to all E-AHPBA members to assess the effects of the pandemic on unit capacity, management of HPB cancers, use of COVID-19 screening and other aspects of service delivery. RESULTS: overall, 145 (25%) members responded. Most units, particularly in COVID-high countries (>100,000 cases) reported insufficient critical care capacity and reduced HPB operating sessions compared to COVID-low countries. Delayed access to cancer surgery necessitated alternatives including increased neoadjuvant chemotherapy for pancreatic cancer and colorectal liver metastases, and locoregional treatments for hepatocellular carcinoma. Other aspects of service delivery including COVID-19 screening and personal protective equipment varied between units and countries. DISCUSSION: This study demonstrates that the COVID-19 pandemic has had a profound adverse impact on the delivery of HPB cancer care across the continents of Europe and Africa. The findings illustrate the need for safe resumption of cancer surgery in a “new” normal world with screening of patients and staff for COVID-19.


title: Transcriptomic analysis of immune response to bacterial lipopolysaccharide in zebra finch (Taeniopygia guttata)

text: BACKGROUND: Despite the convergence of rapid technological advances in genomics and the maturing field of ecoimmunology, our understanding of the genes that regulate immunity in wild populations is still nascent. Previous work to assess immune function has relied upon relatively crude measures of immunocompetence. However, with next-generation RNA-sequencing, it is now possible to create a profile of gene expression in response to an immune challenge. In this study, captive zebra finch (Taeniopygia guttata; adult males) were challenged with bacterial lipopolysaccharide (LPS) or vehicle to stimulate the innate immune system. 2 hours after injection, birds were euthanized and hypothalami, spleen, and red blood cells (RBCs) were collected. Taking advantage of the fully sequenced genome of zebra finch, total RNA was isolated, sequenced, and partially annotated in these tissue/cells. RESULTS: In hypothalamus, there were 707 significantly upregulated transcripts, as well as 564 and 144 in the spleen and RBCs, respectively, relative to controls. Also, 155 transcripts in the hypothalamus, 606 in the spleen, and 61 in the RBCs were significantly downregulated. More specifically, a number of immunity-related transcripts (e.g., IL-1β, RSAD2, SOCS3) were upregulated among tissues/cells. Additionally, transcripts involved in metabolic processes (APOD, LRAT, RBP4) were downregulated. CONCLUSIONS: These results suggest a potential trade-off in expression of genes that regulate immunity and metabolism in birds challenged with LPS. This finding is consistent with a hypothermic response to LPS treatment in small birds. Unlike mammals, birds have nucleated RBCs, and these results support a novel transcriptomic response of avian RBCs to immune challenge. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-019-6016-3) contains supplementary material, which is available to authorized users.


title: The impact of city epidemics on rural labor market: The Korean Middle East Respiratory Syndrome case

text: Abstract This study compared the changes in employment in urban areas in Korea, where a large number of people were quarantined by the Middle East Respiratory Syndrome epidemic, to those in rural areas, where only a small number of people were quarantined using the difference-in-difference approach. The results indicate that the urban labor market experienced a direct effect in terms of a reduction in employment of the group vulnerable to the epidemic while the rural labor market experienced an indirect effect on its economy through a reduction in employment resulting from a decline in consumption and leisure activities. If one looks into the employment in the accommodation and leisure industry, which sustained the most severe blow, dropped to its lowest level right after the Middle East Respiratory Syndrome outbreak. The rural leisure and accommodation industries are highly likely to be dependent on consumption and spending from urban areas. The results suggest that the rural labor market was influenced by the spillover/external effects caused by behavioral changes among people in urban areas due to fear of infection. Thus, this empirical analysis can be used to customize policy to support regions that can be negatively impacted by spillovers due to epidemic in order to respond against economic stresses.


title: Impact of Covid-19 on Digital Transformation and Sustainability in Small and Medium Enterprises (SMEs): A Conceptual Framework

text: This paper aims to develop a framework for sustainability in SMEs. SMEs are most vulnerable to the effects of covid-19. The implementation of social distancing makes people limit activities outside their home, consequently sales turnover decreases. Therefore, SMEs need to change the mindset in running business by using technology transformation. It is believed to continue the sustainability of SMEs. However, some SMEs do not have knowledge about digital skills that are relevant to their business. In fact, during covid-19 condition, online business can result sustainability in their business that can take place now and in the future.


title: Associations Between Hand Hygiene Education and Self-Reported Hand-Washing Behaviors Among Korean Adults During MERS-CoV Outbreak

text: Background. Hand washing is an effective way to prevent transmission of infectious diseases. Education and promotional materials about hand washing may change individuals’ awareness toward hand washing. Infectious disease outbreak may also affect individuals’ awareness. Aims. Our study aimed to examine associations between hand-washing education and self-reported hand-washing behaviors among Korean adults during the year of the Middle East respiratory syndrome (MERS) outbreak. Methods. Data from the 2015 Community Health Survey were used for this study. The total study population comprised 222,599 individuals who were older than 20 years of age. A multiple linear regression model was used to investigate associations between hand hygiene education and self-reported hand-washing behaviors. Subgroup analyses stratified by age, sex, income, and MERS outbreak regions were also performed. Results. Individuals who received hand-washing education or saw promotional materials related to hand washing had significantly higher scores for self-reported use of soap or sanitizer (β = 0.177, P < .0001) and self-reported frequency of hand washing (β = 0.481, P < .0001) than those who did not have such experiences. The effect of hand-washing education on self-reported behavior change was greater among older adults, women, and lower income earners. The effect of hand hygiene education on self-reported use of soap or sanitizer was similar regardless of whether the participants lived in MERS regions. Conclusion. Our findings emphasize the importance of education or promotions encouraging hand washing, especially for older adults, women, and lower income earners. In addition, MERS outbreak itself affected individuals’ awareness of hand-washing behaviors. Well-organized campaigns that consider these factors are needed to prevent infectious diseases.


title: Effectiveness of adjuvanted seasonal influenza vaccines (Inflexal V(®) and Fluad(®)) in preventing hospitalization for influenza and pneumonia in the elderly: A matched case-control study

text: Annual vaccination is the main mean of preventing influenza in the elderly. In order to evaluate the effectiveness of the adjuvanted seasonal influenza vaccines available in Italy in preventing hospitalization for influenza and pneumonia, a matched case-control study was performed in elderly subjects during the 2010–2011 season in Genoa (Italy). Cases and controls were matched in a 1:1 ratio according to gender, age, socio-economic status and type of influenza vaccine. Vaccine effectiveness was calculated as IVE = [(1-OR)x100] and crude odds ratios were estimated through conditional logistic regression models. Adjusted odds ratios were estimated through multivariable logistic models. In the study area, influenza activity was moderate in the 2010–2011 season, with optimal matching between circulating viruses and vaccine strains. We recruited 187 case-control pairs; 46.5% of cases and 79.1% of controls had been vaccinated. The adjuvanted influenza vaccines (Fluad(®) considered together with Inflexal V(®)) were associated with a significant reduction in the risk of hospitalization, their effectiveness being 94.8% (CI 77.1–98.8). Adjusted vaccine effectiveness was 95.2% (CI 62.8–99.4) and 87.8 (CI 0.0–98.9) for Inflexal V(®) and Fluad(®), respectively. Both adjuvanted vaccines proved effective, although the results displayed statistical significance only for Inflexal V(®) (p = 0.004), while for Fluad(®) statistical significance was not reached (p = 0.09). Our study is the first to provide information on the effectiveness of Inflexal V(®) in terms of reducing hospitalizations for influenza or pneumonia in the elderly, and demonstrates that this vaccine yields a high degree of protection and that its use would generate considerable saving for the National Health Service.


title: Characterization of influenza A virus pseudotyped with the spike protein of porcine epidemic diarrhea virus

text: The coronavirus spike protein and the influenza virus hemagglutinin are class I viral membrane fusion proteins. While the two proteins display strong structural conservation and the mechanisms underlying membrane fusion are similar, they share no sequence similarity. Whether they are functionally interchangeable is currently unknown. In this study, we constructed scIAV-S, a single-cycle influenza A virus pseudotyped with the spike protein of porcine epidemic diarrhea virus (PEDV), and demonstrated that this virus could infect cultured cells and trigger massive syncytium formation. Treatment with endocytosis inhibitors did not affect syncytium formation by infected cells. Moreover, the infectivity of scIAV-S was associated with the degree of cell adaptation of PEDV-S. Intriguingly, scIAV-S lacking functional neuraminidase (NA) exhibited substantially higher infectivity, suggesting a pivotal role of the sialic acid in the binding/entry of PEDV. Together, scIAV-S offers a robust platform for the investigation of the entry mechanism of PEDV or, possibly, of other coronaviruses.


title: Molecular detection of bovine coronavirus in a diarrhea outbreak in pasture-feeding Nellore steers in southern Brazil

text: Worldwide diarrhea outbreaks in cattle herds are more frequently detected in calves being that diarrhea outbreaks in adult cattle are not common. Winter dysentery (WD) is a bovine coronavirus (BCoV) enteric infection that is more reported in Northern hemisphere. Seasonal outbreaks of WD in adult cattle occur mainly in dairy cows. WD has not been described in beef cattle herds of tropical countries. This study describes the molecular detection of BCoV in a diarrhea outbreak in beef cattle steers (Nellore) raised on pasture in Parana, southern Brazil. During the outbreak, the farm had about 600 fattening steers. Watery and bloody diarrhea unresponsive to systemic broad-spectrum antibiotic therapy reveals a morbidity rate of approximately 15 %. The BCoV N gene was identified in 42.9 % (6/14) of the diarrheic fecal samples evaluated by semi-nested polymerase chain reaction (SN-PCR) technique. Other enteric microorganisms occasionally identified in adult cattle and evaluated in this study such as bovine groups A, B, and C rotavirus, bovine viral diarrhea virus, bovine torovirus, aichivirus B, and Eimeria sp. were not identified in the fecal samples. To the best knowledge of the authors, this is the first description of the BCoV diagnosis in fecal samples collected in a diarrhea outbreak in adult beef cattle grazing in the grass in a tropical country.


title: Summary of 20 tracheal intubation by anesthesiologists for patients with severe COVID-19 pneumonia: retrospective case series

text: SARS-CoV-2 pandemic is announced and it is very important to share our experience to the critical care community in the early stage. Urgent intubation team was organized by anesthesiologists and was dispatched upon request. We have retrospectively reviewed medical charts of 20 critically ill patients with Covid-19 pneumonia who required tracheal intubation from February 17 to March 19 in Wuhan No.1 hospital, China. We collected their demographics, vital signs, blood gas analysis before and after tracheal intubation, and 7-day outcome after tracheal intubation. Out of 20 patients, 90% were over 60 years old and 15 were with at least one comorbidity. All meet the indication for tracheal intubation announced by treatment expert group. We had successfully intubated all patients using personal protective equipment without circulatory collapse during tracheal intubation. During the observational period, none of 17 anesthesiologists were infected. Although intubation improved SPO(2), reduced PaCO(2) and blood lactate, seven of 20 patients died within 7-days after tracheal intubation. Non-survivors showed significantly lower SPO(2) and higher PaCO(2) and blood lactate compared to survivors. For those who are anticipated to deteriorate severe pneumonia with poor prognosis, earlier respiratory support with tracheal intubation may be advised to improve outcome. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00540-020-02778-8) contains supplementary material, which is available to authorized users.


title: Emerging infectious disease laboratory and diagnostic preparedness to accelerate vaccine development

text: Rapid vaccine development in response to an outbreak of a new emerging infectious disease (EID) is a goal targeted by public health agencies worldwide. This goal becomes more complicated when there are no standardized sets of viral and immunological assays, no accepted and well-characterized samples, standards or reagents, and no approved diagnostic tests for the EID pathogen. The diagnosis of infections is of critical importance to public health, but also in vaccine development in order to track incident infections during clinical trials, to differentiate natural infection responses from those that are vaccine-related and, if called for by study design, to exclude subjects with prior exposure from vaccine efficacy trials. Here we review emerging infectious disease biological standards development, vaccine clinical assay development and trial execution with the recent experiences of MERS-CoV and Zika virus as examples. There is great need to establish, in advance, the standardized reagents, sample panels, controls, and assays to support the rapid advancement of vaccine development efforts in response to EID outbreaks.


title: Kawasaki disease – A common childhood vasculitis

text: Abstract Kawasaki disease (KD) is an acute self-limiting vasculitis of children predominantly affecting the medium sized arteries. The disease was first described by Dr. Tomisaku Kawasaki in 1967 from Japan. KD has now been reported from more than 60 countries and is the commonest cause of acquired heart disease in children in the developed countries. Japan reports the highest incidence of KD at 265/100,000 children below 5 years, followed by Korea and Taiwan. In North America and Europe, the incidence of KD is much lower (9–25/100,000 children below 5) and appears to have plateaued down over the last few decades. The reasons for these differences in epidemiology are not clearly understood. KD has been increasingly reported from India over the last 20 years. At Chandigarh, an incidence of 4.54/100,000 children below 15 years was reported in 2011. However, this was likely to be an underestimate. The etiology of KD remains unknown. Although a genetic basis of KD seems plausible, an intercurrent infectious process seems to act as a trigger for the inflammatory cascade. Like many other vasculitides, the diagnosis of KD is essentially clinical and is based on a set of criteria first elaborated by Dr. Kawasaki himself. However, several children (especially infants) with KD can have incomplete and atypical presentations. This can result in diagnostic and therapeutic delays. Approximately 15–25% children with KD can develop coronary artery abnormalities (CAAs) if left untreated. Two dimensional echocardiography remains the gold standard in detecting CAAs in patients with KD. Dual source CT coronary angiography is a recent advance in accurate detection of CAAs with minimal radiation risk. Intravenous immunoglobulin (2g/kg) remains the drug of choice and is administered as an infusion. Other therapeutic agents that have been used include infliximab, cyclosporine, glucocorticoids, and statins. KD has been associated with several long-term sequelae.


title: Understanding the COVID‐19 coagulopathy spectrum

text: The SARS‐Cov‐2 (COVID‐19) pandemic has already claimed over 200,000 lives. Quite early on in this pandemic, it was recognised that the virus triggers the immune system leading to a cytokine storm in some severely ill patients [1]. This hyper‐responsiveness has been suggested to be the predominant aetiology for clinical deterioration and mortality in patients with this infection [2]. More recently, there have been several reports of increased thrombotic events in these patients [3‐6]. From a laboratory perspective, this hypercoagulability is reflected in the marked elevation of the fibrinolytic marker, D‐dimer, in almost all hospitalised COVID‐19 patients [7]. We must, therefore, ask ourselves what is the link between the extremes of the immune system, presenting as cytokine storm, and the extremes of coagulation, presenting as arterial and venous thromboembolism?


title: Loop‐mediated isothermal amplification for rapid identification of biotypes B and Q of the globally invasive pest Bemisia tabaci, and studying population dynamics

text: BACKGROUND: Bemisia tabaci, the sweetpotato whitefly, is a globally invasive pest that causes serious agricultural damage by transmitting plant viruses. This pest forms a cryptic species complex that displays morphologically indistinguishable biotypes. Among them, the B and Q biotypes are the most important pests worldwide. Because they have different levels of insecticide resistance, these biotypes must be identified in order to achieve proper pest control. Therefore, a convenient, rapid and specific detection method for identifying the two biotypes is necessary. RESULTS: Loop‐mediated isothermal amplification (LAMP) was employed for rapid identification of B. tabaci B and Q biotypes. By combining a quick DNA extraction method, identification of the two biotypes was achieved within 1 h of detection time. The LAMP assay was applied to study the dynamics of B. tabaci biotypes both in the field and in greenhouses. It was found that, while temperature may be important for population dynamics of the whitefly in the field, population dynamics in greenhouse conditions may be influenced by the types of insecticide. CONCLUSION: The newly designed LAMP assay is a simple, rapid and accurate method for identifying the B and Q biotypes. It can be conducted by non‐specialists and can contribute to pest management. Copyright © 2012 Society of Chemical Industry


title: Islet Xeno/transplantation and the risk of contagion: local responses from Canada and Australia to an emerging global technoscience

text: This paper situates the public debate over the use of living animal organs and tissue for human therapies within the history of experimental islet transplantation. Specifically, the paper compares and contrasts the Canadian and Australian responses on xenotransplantation to consider what lessons can be learnt about the regulation of a complex and controversial biotechnology. Sobbrio and Jorqui described public engagement on xenotransplantation in these countries as ‘important forms of experimental democracy.’ While Canada experimented with a novel nation-wide public consultation, Australia sought public input within the context of a national inquiry. In both instances, the outcome was a temporary moratorium on all forms of clinical xenotransplantation comparable to the policies adopted in some European countries. In addition, the Australian xenotransplantation ban coincided with a temporary global ban on experimental islet allotransplantation in 2007. Through historical and comparative research, this paper investigates how public controversies over organ and tissue transplantation can inform our understanding of the mediation of interspeciality and the regulation of a highly contested technoscience. It offers an alternative perspective on the xenotransplantation controversy by exploring the ways in which coinciding moratoriums on islet allograft and xenograft challenge, complicate and confound our assumptions regarding the relationships between human and animal, between routine surgery and clinical experimentation, between biomedical science and social science, and between disease risks and material contagion.


title: Evaluation of disaster preparedness for mass casualty incidents in private hospitals in Central Saudi Arabia

text: OBJECTIVES: To identify and describe the hospital disaster preparedness (HDP) in major private hospitals in Riyadh, Saudi Arabia. METHODS: This is an observational cross-sectional survey study performed in Riyadh city, Saudi Arabia between December 2015 and April 2016. Thirteen major private hospitals in Riyadh with more than 100 beds capacity were included in this investigation. RESULTS: The 13 hospitals had HDP plan and reported to have an HDP committee. In 12 (92.3%) hospitals, the HDP covered both internal and external disasters and HDP was available in every department of the hospital. There were agreements with other hospitals to accept patients during disasters in 9 facilities (69.2%) while 4 (30.8%) did not have such agreement. None of the hospitals conducted any unannounced exercises in previous year. CONCLUSION: Most of the weaknesses were apparent particularly in the education, training and monitoring of the hospital staff to the preparedness for disaster emergency occasion. Few hospitals had conducted an exercise with casualties, few had drilled evacuation of staff and patients in the last 12 months, and none had any unannounced exercise in the last year.


title: Design, synthesis, and evaluation of trifluoromethyl ketones as inhibitors of SARS-CoV 3CL protease

text: Abstract A series of trifluoromethyl ketones as SARS-CoV 3CL protease inhibitors was developed. The inhibitors were synthesized in four steps from commercially available compounds. Three different amino acids were explored in the P1-position and in the P2–P4 positions varying amino acids and long alkyl chain were incorporated. All inhibitors were evaluated in an in vitro assay using purified enzyme and fluorogenic substrate peptide. One of the inhibitors showed a time-dependent inhibition, with a K i value of 0.3μM after 4h incubation.


title: Pharmacist-led Medication Counseling for Patients Undergoing Hemodialysis: A Path to Better Adherence

text: Objective: The primary objective was to assess the satisfaction of patients undergoing hemodialysis regarding counseling services provided by pharmacists. The secondary objectives were to compare the effect of years on dialysis and the presence of comorbidities on patient satisfaction. Methods: A total of 138 patients were included in the study, and all demographic and clinical variables were retrieved from the dialysis unit records of King Abdulaziz Medical City over a period of 4 months from July to October 2015. Chi-square test and Fisher’s exact test were used for group comparisons at a significance level of 0.05. Results: Most patients aged between 51 and 75 years and had been on dialysis for 1 to 5 years; 94.9% of them had comorbidities. The overall satisfaction of patients toward pharmacy services was excellent (77.5%), and approximately 38.4% of patients thought that pharmacists were providing clear information about their prescribed medications. In addition, 55.8% of the patients did not know that hemodialysis could affect the efficacy of their medications. Conclusions: Patients undergoing hemodialysis were somewhat satisfied with the counseling provided by the pharmacist. Moreover, there is a need for educational programs for patients undergoing hemodialysis that would increase awareness among hospital pharmacists to improve patients’ medication knowledge.


title: Truthful but Misleading: Advanced Linguistic Strategies for Lying Among Children

text: We explored whether children could apply linguistic strategies for lying, i.e., manipulating linguistic content of speech to mislead others. We announced a knowledge-test entailing prizes in the classrooms of a primary school and a middle school. Altogether 79 Chinese children (6–18 years) voluntarily participated in the test: listening to a series of animal sounds before guessing the names of the animals. Meanwhile, behind the participants, a video was playing images that ostensibly corresponded to the sounds being played. In fact, this was not necessarily the case, i.e., some items cannot be solved because the sounds played are not from any animal but machine-synthesized. Participants were instructed not to look back at the video. However, 51 children peeked at the video for the unsolvable items, although the peeking behavior decreased with age. Moreover, when explaining how they correctly guessed the unsolvable items, children as young as 6 years old were able to apply a linguistic strategy (i.e., “capability attribution”) for lying. Besides “capability attribution,” Children also applied “fortune attribution” and “topic shift” for lying. Finally, “fortune attribution” and “topic shift” increased with age. Therefore, educators need to be aware that children are able to apply verbal strategies for lying that could involve truthful statements (i.e., “topic shift”) or statements that are difficult to be proved as untruthful (i.e., “fortune attribution”).


title: Crystal structure of dengue virus methyltransferase without S-adenosyl-L-methionine

text: Abstract Flavivirus methyltransferase is a genetically-validated antiviral target. Crystal structures of almost all available flavivirus methyltransferases contain S-adenosyl-L-methionine (SAM), the methyl donor molecule that co-purifies with the enzymes. This raises a possibility that SAM is an integral structural component required for the folding of dengue virus (DENV) methyltransferase. Here we exclude this possibility by solving the crystal structure of DENV methyltransferase without SAM. The SAM ligand was removed from the enzyme through a urea-mediated denaturation-and-renaturation protocol. The crystal structure of the SAM-depleted enzyme exhibits a vacant SAM-binding pocket, with a conformation identical to that of the SAM-enzyme co-crystal structure. Functionally, equivalent enzymatic activities (N-7 methylation, 2′-O methylation, and GMP-enzyme complex formation) were detected for the SAM-depleted and SAM-containing recombinant proteins. These results clearly indicate that the SAM molecule is not an essential component for the correct folding of DENV methyltransferase. Furthermore, the results imply a potential antiviral approach to search for inhibitors that can bind to the SAM-binding pocket and compete against SAM binding. To demonstrate this potential, we have soaked crystals of DENV methyltransferase without a bound SAM with the natural product Sinefungin and show that preformed crystals are capable of binding ligands in this pocket.


title: P136 Combined action of type I and type III IFN restricts initial replication of SARS-coronavirus in the lung but fails to inhibit systemic virus spread

text: Introduction STAT1-deficient mice are more susceptible to infection with SARS-Coronavirus (SARS-CoV) than type I IFN receptor-deficient mice. The increased susceptibility of STAT1-deficient mice is potentially due to the lack of functional type III IFN (IFN-λ) signalling. Methods We used mice lacking functional receptors for both type I and type III IFN (dKO) to evaluate the possibility that type III IFN plays a decisive role in SARS-CoV protection. Results We found that viral peak titres in lungs of dKO and STAT1-deficient mice were similar, although significantly higher than in wild-type mice. The kinetics of viral clearance from the lung was also comparable in dKO and STAT1-deficient mice. Surprisingly, however, infected dKO mice remained healthy, whereas infected STAT1-deficient mice developed liver pathology and eventually succumbed to neurological disease. Conclusion Our data suggest that the failure of STAT1-deficient mice to efficiently control initial SARS-CoV replication in the lung is due to impaired type I and type III IFN signaling, whereas the failure to control subsequent systemic viral spread is due to unrelated defects in STAT1-deficient mice.


title: Coronavirus leader‐RNA‐primed transcription: An alternative mechanism to RNA splicing

text: Many viral and cellular mRNA species contain a leader sequence derived from a distant upstream site on the same gene by a process of RNA splicing. This process usually involves either nuclear functions or self‐splicing of RNA molecules. Coronavirus, a cytoplasmic RNA virus, unfolds yet another mechanism of joining RNA, which involves the use of a free leader RNA molecule. This molecule is synthesized and dissociates from the template RNA, and subsequently reassociates with the template RNA at down‐stream initiation sites of subgenomic mRNAs to serve as the primer for transcription. This leader‐primed transcriptional process thus generates viral mRNAs with a fused leader sequence. A similar mechanism might also operate in the mRNA transcription of African trypanosomes.


title: Online Gaming During the COVID-19 Pandemic in India: Strategies for Work-Life Balance

text: ARDS, first described in 1967, is the commonest form of acute severe hypoxemic respiratory failure Despite considerable advances in our knowledge regarding the pathophysiology of ARDS, insights into the biologic mechanisms of lung injury and repair, and advances in supportive care, particularly ventilatory management, there remains no effective pharmacological therapy for this syndrome Hospital mortality at 40% remains unacceptably high underlining the need to continue to develop and test therapies for this devastating clinical condition The purpose of the review is to critically appraise the current status of promising emerging pharmacological therapies for patients with ARDS and potential impact of these and other emerging therapies for COVID-19-induced ARDS We focus on drugs that: (1) modulate the immune response, both via pleiotropic mechanisms and via specific pathway blockade effects, (2) modify epithelial and channel function, (3) target endothelial and vascular dysfunction, (4) have anticoagulant effects, and (5) enhance ARDS resolution We also critically assess drugs that demonstrate potential in emerging reports from clinical studies in patients with COVID-19-induced ARDS Several therapies show promise in earlier and later phase clinical testing, while a growing pipeline of therapies is in preclinical testing The history of unsuccessful clinical trials of promising therapies underlines the challenges to successful translation Given this, attention has been focused on the potential to identify biologically homogenous subtypes within ARDS, to enable us to target more specific therapies 'precision medicines ' It is hoped that the substantial number of studies globally investigating potential therapies for COVID-19 will lead to the rapid identification of effective therapies to reduce the mortality and morbidity of this devastating form of ARDS


title: Sources et devenir des micro-organismes pathogènes dans les environnements aquatiques

text: Résumé Un grand nombre d’infections humaines d’origine hydrique sont causées par des micro-organismes qu’il s’agisse de virus, de bactéries ou encore de protozoaires. Ces micro-organismes sont soit naturellement présents dans les environnements aquatiques, soit transférés au sein de ces derniers via des sources d’origine fécale. Ils séjournent dans ces environnements pendant un temps plus ou moins long avant de contaminer un nouvel hôte. Les environnements aquatiques sont soumis à une forte variabilité de leurs paramètres physicochimiques et abritent une vaste communauté microbienne plus ou moins adaptée à ces changements environnementaux. Ainsi les interactions entre les micro-organismes, qu’ils soient pathogènes ou non, sont nombreuses et certaines d’entre elles sont encore aujourd’hui méconnues. L’objectif de cet article est de présenter les interactions connues entre certains micro-organismes pathogènes et le milieu naturel en abordant notamment la diversité des sources de contamination, leur contribution dans la pollution microbiologique des milieux aquatiques, et le devenir des pathogènes dans des environnements notamment au travers des stratégies de survie que certains sont capables de développer. Summary A large number of human waterborne infections are caused by microorganisms including viruses, bacteria or protozoa. These microorganisms are either naturally presents in aquatic environments, or come from fecal sources. They may stay in aquatic ecosystems for a long time before contaminating a new host. Aquatic environments are subjected to high variability of physico- chemical parameters. They include a microbial community that is more or less adapted to these environmental changes. Thus, numerous interactions occur between microorganisms, which are pathogenic or not, and most of them are still unknown. This review focused on interactions between pathogen microorganisms and their environment. More specifically we addressed the question of the diversity of the sources of contamination, their contribution to the microbiological pollution of the aquatic environment, and the ability of some pathogens to survive adverse environmental conditions.


title: Acute effects of viral respiratory tract infections on sputum bacterial density during CF pulmonary exacerbations

text: Abstract Background Airway proliferation of Pseudomonas aeruginosa bacteria is thought to trigger CF exacerbations and may be affected by the presence of viral infections. Methods A 2-year prospective study was conducted on 35 adults with CF. P. aeruginosa sputum density was analyzed during stable, exacerbation and post exacerbation assessments. Upon exacerbation, samples were sent for PCR detection of respiratory viruses and the sputum density of P. aeruginosa in patients with a viral infection versus those without was compared. Results Twenty-two patients experienced 30 exacerbations during the study period; 50% were associated with a viral infection. There was no change in sputum density of P. aeruginosa from the stable to exacerbation state when measured by quantitative culture or by PCR. Virus-associated exacerbations did not result in significant increases in P. aeruginosa sputum density compared to non-viral exacerbations. Conclusion Sputum density of P. aeruginosa was not increased at the time of CF exacerbation and was not influenced by the presence of viral infection.


title: Pulmonary Infection with Lophomonas blattarum

text: OBJECTIVE: To describe the characteristics of Lophomonas blattarum infection in children based on a retrospective review of medical records data from Beijing Children’s Hospital, Capital Medical University, China. METHODS: This study included 53 cases from July 2014 through December 2016. The data were tabulated and statistically analysed in a Microsoft Excel spreadsheet and SPSS 17.0. RESULTS: The average age of the 53 patients was 7.10 ± 0.56 years, and the male/female ratio was 3:2.3. The most common clinical manifestation was cough, and almost half of the patients had fever. Furthermore, all patients were treated with metronidazole and recovered. CONCLUSIONS: For children who have had long-term respiratory symptoms, the possibility of Lophomonas blattarum infection should be ruled out. Metronidazole is effective in treating L. blattarum infection in children.


title: Quantitative detection of human Malawi polyomavirus in nasopharyngeal aspirates, sera, and feces in Beijing, China, using real-time TaqMan-based PCR

text: BACKGROUND: Human Malawi polyomavirus (MWPyV) was discovered in 2012, but its prevalence and clinical characteristics are largely unknown. METHODS: We used real-time TaqMan-based PCR to detect MWPyV in the feces (n = 174) of children with diarrhea, nasopharyngeal aspirates (n = 887) from children with respiratory infections, and sera (n = 200) from healthy adults, and analyzed its clinical characteristics statistically. All the MWPyV-positive specimens were also screened for other common respiratory viruses. RESULTS: Sixteen specimens were positive for MWPyV, including 13 (1.47%) respiratory samples and three (1.7%) fecal samples. The samples were all co-infected with other respiratory viruses, most commonly with influenza viruses (69.2%) and human coronaviruses (30.7%). The MWPyV-positive children were diagnosed with bronchopneumonia or viral diarrhea. They ranged in age from 12 days to 9 years, and the most frequent symptoms were cough and fever. CONCLUSIONS: Real-time PCR is an effective tool for the detection of MWPyV in different types of samples. MWPyV infection mainly occurs in young children, and fecal–oral transmission is a possible route of its transmission. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-017-0817-2) contains supplementary material, which is available to authorized users.


Thinking “outside the box”


title: Viruses and Gram-negative bacilli dominate the etiology of community-acquired pneumonia in Indonesia, a cohort study

text: Abstract Objective Knowledge about the etiology of community-acquired pneumonia (CAP) is essential for adequate management. Presently, few studies about CAP are available from Southeast Asia. This study aimed to investigate the etiology, severity, and outcome of CAP in the most populous Southeast Asia country, Indonesia. Methods From October 2007 to April 2009, adult patients admitted with CAP to two hospitals in Semarang, Indonesia, were included to detect the etiology of CAP using a full range of diagnostic methods. The severity of disease was classified according to the Pneumonia Severity Index (PSI). The outcome was assessed as 30-day mortality. Results In total, 148 consecutive patients with CAP were included. Influenza virus (18%), Klebsiella pneumoniae (14%), and Streptococcus pneumoniae (13%) were the most common agents identified. Other Gram-negative bacilli, Mycobacterium tuberculosis, Chlamydia pneumoniae each accounted for 5%. The bacteria presented wild type antibiotic susceptibility profiles. Forty-four percent of subjects were high-risk patients (PSI class IV-V). The mortality rate (30%) was significantly associated with disease severity score (P<0.001), and with failure to establish an etiological diagnosis (P=0.027). No associations were found between etiology and underlying diseases, PSI class, nor mortality. Conclusions Viruses and Gram-negative bacilli are dominant causes of CAP in this region, more so than S. pneumoniae. Most of the bacteria have wild type susceptibility to antimicrobial agents. Patients with severe disease and those with unknown etiology have a higher mortality risk.


title: Endoribonuclease activities of porcine reproductive and respiratory syndrome virus nsp11 was essential for nsp11 to inhibit IFN-β induction

text: Abstract Previous studies have shown that PRRSV nsp11, which was an endoribonuclease, was an interferon antagonist, however, the mechanism that nsp11 inhibited IFN-β production was unclear. To explore whether the endoribonuclease was required for nsp11 to disrupt the IFN-β production, substitutions of the presumed catalytic histidine and lysine residues of nsp11 were introduced into plasmid pcDNA 3.1-FLAG. The results showed that mutation that inactivated endoribonuclease made nsp11 lose its ability to inhibit Poly(I:C)-induced IFN-β promoter activity. In conclusion, our present work indicated that the endoribonuclease activity of nsp11 was essential for nsp11 to inhibit the IFN-β induction.


title: Oral recombinant Lactobacillus vaccine targeting the intestinal microfold cells and dendritic cells for delivering the core neutralizing epitope of porcine epidemic diarrhea virus

text: BACKGROUND: Porcine epidemic diarrhea caused by porcine epidemic diarrhea virus (PEDV) has led to serious economic losses to the swine industry worldwide. In this study, an oral recombinant Lactobacillus casei vaccine against PEDV infection targeting the intestinal microfold (M) cells and dendritic cells (DCs) for delivering the core neutralizing epitope (COE) of PEDV spike protein was developed with M cell-targeting peptide (Col) and dendritic cell-targeting peptide (DCpep). The immunogenicity of the orally administered recombinant strains was evaluated. RESULTS: After immunization, significantly higher levels of anti-PEDV specific IgG antibodies with PEDV neutralizing activity in the sera and mucosal sIgA antibodies in the tractus genitalis, intestinal mucus, and stools were detected in mice orally administered with the recombinant strain pPG-COE-Col-DCpep/L393, which expressed DCpep and Col targeting ligands fused with the PEDV COE antigen, compared to mice orally immunized with the recombinant strain pPG-COE/L393 without the DCpep and Col targeting ligands. Moreover, in response to restimulation with the PEDV COE antigen in vitro, a significant difference in splenocyte proliferation response and Th2-associated cytokine IL-4 level was observed in the group of mice orally immunized with pPG-COE-Col-DCpep/L393 (p < 0.05) compared to the groups of mice that received pPG-COE-Col/L393 and pPG-COE-DCpep/L393, respectively. CONCLUSIONS: The intestinal M cells- and DCs-targeting oral delivery of genetically engineered Lactobacillus expressing the COE antigen of PEDV can efficiently induce anti-PEDV mucosal, humoral, and cellular immune responses via oral administration, suggesting a promising vaccine strategy against PEDV infection. [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12934-018-0861-7) contains supplementary material, which is available to authorized users.


title: Rabies outbreak in African Wild Dogs (Lycaon pictus) in the Tuli region, Botswana: Interventions and management mitigation recommendations

text: Abstract We describe an outbreak of rabies in a pack of African wild dogs (Lycaon pictus) in the Limpopo-Lipadi Private Game and Wilderness Reserve in the Tuli region of south-eastern Botswana. We define the pack’s behavioural response to the disease, clinical signs, and management interventions undertaken and make recommendations to mitigate against future disease outbreaks of this nature. The outbreak, which occurred in late 2014 and early 2015, resulted in the death or disappearance of 29 individuals out of a pack of 35 wild dogs. The disruption to the social structure within the pack, the behaviour of the animals and clinical signs were similar to that documented during previous rabies outbreaks amongst African wild dogs in Southern and East Africa in recent years. Management interventions taken during the outbreak were aimed at preventing extirpation of the pack and reducing the risk of further disease spread to other mammals in the reserve.


title: IL-6: relevance for immunopathology of SARS-CoV-2

text: COVID-19 mortality is strongly associated with the development of severe pneumonia and acute respiratory distress syndrome with the worst outcome resulting in cytokine release syndrome and multiorgan failure. It is becoming critically important to identify at the early stage of the infection those patients who are prone to develop the most adverse effects. Elevated systemic interleukin-6 levels in patients with COVID-19 are considered as a relevant parameter in predicting most severe course of disease and the need for intensive care. This review discusses the mechanisms by which IL-6 may possibly contribute to disease exacerbation and the potential of therapeutic approaches based on anti-IL-6 biologics.


title: Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China

text: Previous studies have showed clinical characteristics of patients with the 2019 novel coronavirus disease (COVID-19) and the evidence of person-to-person transmission. Limited data are available for asymptomatic infections. This study aims to present the clinical characteristics of 24 cases with asymptomatic infection screened from close contacts and to show the transmission potential of asymptomatic COVID-19 virus carriers. Epidemiological investigations were conducted among all close contacts of COVID-19 patients (or suspected patients) in Nanjing, Jiangsu Province, China, from Jan 28 to Feb 9, 2020, both in clinic and in community. Asymptomatic carriers were laboratory-confirmed positive for the COVID-19 virus by testing the nucleic acid of the pharyngeal swab samples. Their clinical records, laboratory assessments, and chest CT scans were reviewed. As a result, none of the 24 asymptomatic cases presented any obvious symptoms while nucleic acid screening. Five cases (20.8%) developed symptoms (fever, cough, fatigue, etc.) during hospitalization. Twelve (50.0%) cases showed typical CT images of ground-glass chest and 5 (20.8%) presented stripe shadowing in the lungs. The remaining 7 (29.2%) cases showed normal CT image and had no symptoms during hospitalization. These 7 cases were younger (median age: 14.0 years; P=0.012) than the rest. None of the 24 cases developed severe COVID-19 pneumonia or died. The median communicable period, defined as the interval from the first day of positive nucleic acid tests to the first day of continuous negative tests, was 9.5 days (up to 21 days among the 24 asymptomatic cases). Through epidemiological investigation, we observed a typical asymptomatic transmission to the cohabiting family members, which even caused severe COVID-19 pneumonia. Overall, the asymptomatic carriers identified from close contacts were prone to be mildly ill during hospitalization. However, the communicable period could be up to three weeks and the communicated patients could develop severe illness. These results highlighted the importance of close contact tracing and longitudinally surveillance via virus nucleic acid tests. Further isolation recommendation and continuous nucleic acid tests may also be recommended to the patients discharged. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s11427-020-1661-4 and is accessible for authorized users.


title: Outbreak of COVID-19 in a family, Wenzhou, China

text: Since December 2019, China has experienced a widespread outbreak of COVID-19. However, at the early stage of outbreak, investigations revealed a variety of patterns resulting in the transmission of COVID-19. Thus, it is essential to understand the transmission types and the potential for sustained human-to-human transmission. Moreover, the information regarding the characteristics of transmission helps in coordinating the current screening programme, and controlling and containing measures, and also, helps in deciding the appropriate quarantine duration. Thus, this investigation reports an outbreak of COVID-19 in a family residing in Wenzhou, Zhejiang, China during the month of January−February 2020.