title: Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis

text: BACKGROUND: Coronavirus disease 2019 (COVID-19) is a novel infectious disease with lack of established laboratory markers available to evaluate illness severity. In this study, we investigate whether platelet count could differentiate between COVID-19 patients with or without severe disease. Additionally, we evaluate if thrombocytopenia is associated with severe COVID-19. METHODS: An electronic search in Medline, Scopus and Web of Science was performed to identify studies reporting data on platelet count in COVID-19 patients. A meta-analysis was performed, with calculation of weighted mean difference (WMD) of platelet number in COVID-19 patients with or without severe disease and odds ratio (OR) of thrombocytopenia for severe form of COVID-19. RESULTS: Nine studies with 1779 COVID-19 patients, 399 (22.4%) with severe disease, were included in the meta-analysis. The pooled analysis revealed that platelet count was significantly lower in patients with more severe COVID-19 (WMD -31×10(9)/L; 95% CI, from -35 to -29×10(9)/L). A subgroup analysis comparing patients by survival, found an even lower platelet count was observed with mortality (WMD, -48×10(9)/L; 95% CI, -57 to -39×10(9)/L. In the four studies (n=1427) which reported data on rate of thrombocytopenia, a low platelet count was associated with over fivefold enhanced risk of severe COVID-19 (OR, 5.1; 95% CI, 1.8-14.6). CONCLUSIONS: Low platelet count is associated with increased risk of severe disease and mortality in patients with COVID-19, and thus should serve as clinical indicator of worsening illness during hospitalization.


title: Repeated avian infectious bronchitis virus infections within a single chicken farm

text: Genotyping of avian infectious bronchitis virus (IBV) was performed on trachea and kidney samples of six chickens obtained from a single farm in Japan. Using two primer sets targeting the spike (S) protein gene, the S1 and S2 regions of DNA fragments were amplified. Sequences of amplified S1 fragments extracted from both organs were identical among the six chickens, showing a JP-I genotype. Sequences of amplified S2 fragments differed between trachea and kidney samples. The kidney profile showed a group IV genotype, whereas the trachea profile showed an unclassified group. This result showed that two different IBVs infected the six chickens. The first IBV infection induced poor protective immunity in this farm, permitting a second IBV infection to occur.


Advancing Priority Research on the Middle East Respiratory Syndrome Coronavirus


title: Prokaryotic expression of antibodies and affibodies

text: Abstract Recent advances have been made in the development of systems for the display and expression of recombinant antibodies and affibodies in filamentous phages, Escherichia coli and other prokaryotic cells. Emphasis has been placed on improving phage and phagemid vectors, alternative systems for expression in different cellular compartments (e.g. the outer membrane, periplasm, cytoplasm and extracellular secretion) and novel multimerization systems for generating bivalent or multivalent binding molecules.


title: COVID-19 diagnostic approaches: different roads to the same destination

text: “SARS-CoV2”, a previously unknown strain of coronaviruses caused a severe respiratory disease called Coronavirus disease (COVID-19) which emerged from Wuhan city of China on 30 December 2019, and declared as Global health problem by World Health Organisation within a month. In less than two and half months (11 March, 2020) it was declared as a pandemic disease due to its rapid spreading ability, it covered more than 211 countries infecting around 1.7 million persons and claiming around 1.1 lakhs lives within merely 100 days of its emergence. Containment of the infection of this virus is the only available measure to control the disease as no vaccine or specific antiviral treatment is available. Confirmed detection of the virus followed by isolation of the infected person at the earliest possible is the only measure to prevent this disease. Although there are number of methods available for detection of virus and to combat this disease in the present pandemic situation, but these available diagnostic methods have their own limitations. The speedy and exponential global spread of this disease strongly urges the fast and economic diagnostics tools. Additional to the available diagnostic methods, there is a sudden surge for development of various of methods and platforms to diagnose the COVID-19. The review summarized the advantage and disadvantage of various diagnostic approaches being used presently for COVID-19, newer detection methods in developmental stage and the feasibility of advanced platforms like newer nano-sensor based on-the-spot detection technologies.


title: SARS-CoV-2-mediated inflammatory response in lungs: should we look at RAGE?

text: The novel coronavirus disease (COVID-19) pandemic is placing significant strains on health systems, scientific communities, essential public services, and economies all over the world. In this context, the world´s scientific biomedical establishment is unleashing an unprecedented response to the COVID-19 pandemic. This is a battle against time, considering the thousands of human lives are lost every day. In this commentary, based on a very recent research report, we intend to highlight how a new mechanism describing the RAGE transactivation produced by Ang II-mediated ATR1 activation can run continuously and thus, reinforcing a sustained inflammation in lungs, due to the SARS-Cov-2-mediated imbalance of the ACE/And II/ATR1 pathway.


title: IFITM Proteins Inhibit Entry Driven by the MERS-Coronavirus Spike Protein: Evidence for Cholesterol-Independent Mechanisms

text: The interferon-inducible transmembrane (IFITM) proteins 1, 2 and 3 inhibit the host cell entry of several enveloped viruses, potentially by promoting the accumulation of cholesterol in endosomal compartments. IFITM3 is essential for control of influenza virus infection in mice and humans. In contrast, the role of IFITM proteins in coronavirus infection is less well defined. Employing a retroviral vector system for analysis of coronavirus entry, we investigated the susceptibility of human-adapted and emerging coronaviruses to inhibition by IFITM proteins. We found that entry of the recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV) is sensitive to inhibition by IFITM proteins. In 293T cells, IFITM-mediated inhibition of cellular entry of the emerging MERS- and SARS-CoV was less efficient than blockade of entry of the globally circulating human coronaviruses 229E and NL63. Similar differences were not observed in A549 cells, suggesting that cellular context and/or IFITM expression levels can impact inhibition efficiency. The differential IFITM-sensitivity of coronaviruses observed in 293T cells afforded the opportunity to investigate whether efficiency of entry inhibition by IFITMs and endosomal cholesterol accumulation correlate. No such correlation was observed. Furthermore, entry mediated by the influenza virus hemagglutinin was robustly inhibited by IFITM3 but was insensitive to accumulation of endosomal cholesterol, indicating that modulation of cholesterol synthesis/transport did not account for the antiviral activity of IFITM3. Collectively, these results show that the emerging MERS-CoV is a target of the antiviral activity of IFITM proteins and demonstrate that mechanisms other than accumulation of endosomal cholesterol can contribute to viral entry inhibition by IFITMs.


title: Saikosaponin C exerts anti-HBV effects by attenuating HNF1α and HNF4α expression to suppress HBV pgRNA synthesis

text: OBJECTIVE: Saikosaponin c (SSc), a compound purified from the traditional Chinese herb of Radix Bupleuri was previously identified to exhibit anti-HBV replication activity. However, the mechanism through which SSc acts against HBV remains unknown. In this study, we investigated the mechanism of SSc mediated anti-HBV activity. METHODS: HepG2.2.15 cells were cultured at 37 ℃ in the presence of 1–40 μg/mL of SSc or DMSO as a control. The expression profile of HBV markers, cytokines, HNF1α and HNF4α were investigated by real-time quantitative PCR, Elisa, Western blot and Dot blotting. Knockdown of HNF1α or HNF4α in HepG2.2.15 cells was mediated by two small siRNAs specifically targeting HNF1α or HNF4α. RESULTS: We found that SSc stimulates IL-6 expression, leading to attenuated HNF1α and HNF4α expression, which further mediates suppression of HBV pgRNA synthesis. Knockdown of HNF1α or HNF4α in HepG2.2.15 cells by RNA interference abrogates SSc’s anti-HBV role. Moreover, SSc is effective to both wild-type and drug-resistant HBV mutants. CONCLUSION: SSc inhibits pgRNA synthesis by targeting HNF1α and HNF4α. These results indicate that SSc acts as a promising compound for modulating pgRNA transcription in the therapeutic strategies against HBV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00011-019-01284-2) contains supplementary material, which is available to authorized users.


title: Review of Artificial Intelligence Techniques in Imaging Data Acquisition, Segmentation and Diagnosis for COVID-19

text: (This paper was submitted as an invited paper to IEEE Reviews in Biomedical Engineering on April 6, 2020.) The pandemic of coronavirus disease 2019 (COVID-19) is spreading all over the world. Medical imaging such as X-ray and computed tomography (CT) plays an essential role in the global fight against COVID-19, whereas the recently emerging artificial intelligence (AI) technologies further strengthen the power of the imaging tools and help medical specialists. We hereby review the rapid responses in the community of medical imaging (empowered by AI) toward COVID-19. For example, AI-empowered image acquisition can significantly help automate the scanning procedure and also reshape the workflow with minimal contact to patients, providing the best protection to the imaging technicians. Also, AI can improve work efficiency by accurate delination of infections in X-ray and CT images, facilitating subsequent quantification. Moreover, the computer-aided platforms help radiologists make clinical decisions, i.e., for disease diagnosis, tracking, and prognosis. In this review paper, we thus cover the entire pipeline of medical imaging and analysis techniques involved with COVID-19, including image acquisition, segmentation, diagnosis, and follow-up. We particularly focus on the integration of AI with X-ray and CT, both of which are widely used in the frontline hospitals, in order to depict the latest progress of medical imaging and radiology fighting against COVID-19.


title: Enteric viruses in Brazilian turkey flocks: Single and multiple virus infection frequency according to age and clinical signs of intestinal disease

text: Poult enteritis complex has been associated with enteritis and reduction in growth rates in commercial turkeys worldwide. Intestinal samples from 76 turkey flocks from different Brazilian states affected or not with intestinal disorders were evaluated for the presence of adenovirus groups 1 and 2 (TAV), astrovirus types 1 and 2 (TAstV-1 and TAstV-2), turkey coronavirus (TCoV), reovirus, rotavirus, and avian nephritis virus (ANV) using PCR. The percentage of positive samples was categorized according to the geographic origin, age of the flocks, and presence of clinical signs of intestinal disease. The percentage of samples that were positive for at least one virus was 93.4%, whereas the percentage of samples that were positive for more than one virus was 69.7%. An average of 3.20 viruses per sample was detected in turkeys in the growing phase of the production cycle (1 to 4 wk of age). The TAstV-1 and TCoV were the most frequently observed viruses in growing phase turkeys and occurred simultaneously in 85% of these samples. In turkeys in the finishing phase of development (5 to 18 wk), a lower average number of viruses was observed (2.41), and the most frequent viruses isolated in these turkeys were TAstV-1 (57.1%) and rotavirus (51.8%). Overall, every virus was detected more frequently in growing phase turkeys than in finishing phase turkeys with the exception of TAV. Samples from flocks exhibiting clinical signs of intestinal disease showed a higher rate of positivity, and TAstV-1, TAstV-2, and TCoV were the most frequently occurring viruses in this cohort. Birds without clinical signs most frequently harbored TAstV-1 and rotavirus. Future studies should focus on the description and elucidation of the role of each virus, as well as the pathogenic and immunological implications of the different combinations of viruses in turkeys.


title: Autophagy, antiviral immunity, and viral countermeasures

text: The autophagy pathway likely evolved not only to maintain cellular and tissue homeostasis but also to protect cells against microbial attack. This conserved mechanism by which cytoplasmic cargo is delivered to the endolysosomal system is now recognized as a central player in coordinating the host response to diverse intracellular pathogens, including viruses. As an endolysosomal delivery system, autophagy functions in the transfer of viruses from the cytoplasm to the lysosome where they are degraded, in the transfer of viral nucleic acids to endosomal sensors for the activation of innate immunity, and in the transfer of endogenous viral antigens to MHC class II compartments for the activation of adaptive immunity. Viruses have, in turn, evolved different strategies to antagonize, and potentially, to exploit the host autophagic machinery. Moreover, through mechanisms not yet well understood, autophagy may dampen host innate immune and inflammatory responses to viral infection. This review highlights the roles of autophagy in antiviral immunity, viral strategies to evade autophagy, and potential negative feedback functions of autophagy in the host antiviral response.


title: Inhibition of a Putative Dihydropyrimidinase from Pseudomonas aeruginosa PAO1 by Flavonoids and Substrates of Cyclic Amidohydrolases

text: Dihydropyrimidinase is a member of the cyclic amidohydrolase family, which also includes allantoinase, dihydroorotase, hydantoinase, and imidase. These metalloenzymes possess very similar active sites and may use a similar mechanism for catalysis. However, whether the substrates and inhibitors of other cyclic amidohydrolases can inhibit dihydropyrimidinase remains unclear. This study investigated the inhibition of dihydropyrimidinase by flavonoids and substrates of other cyclic amidohydrolases. Allantoin, dihydroorotate, 5-hydantoin acetic acid, acetohydroxamate, orotic acid, and 3-amino-1,2,4-triazole could slightly inhibit dihydropyrimidinase, and the IC(50) values of these compounds were within the millimolar range. The inhibition of dihydropyrimidinase by flavonoids, such as myricetin, quercetin, kaempferol, galangin, dihydromyricetin, and myricitrin, was also investigated. Some of these compounds are known as inhibitors of allantoinase and dihydroorotase. Although the inhibitory effects of these flavonoids on dihydropyrimidinase were substrate-dependent, dihydromyricetin significantly inhibited dihydropyrimidinase with IC(50) values of 48 and 40 μM for the substrates dihydrouracil and 5-propyl-hydantoin, respectively. The results from the Lineweaver−Burk plot indicated that dihydromyricetin was a competitive inhibitor. Results from fluorescence quenching analysis indicated that dihydromyricetin could form a stable complex with dihydropyrimidinase with the K (d) value of 22.6 μM. A structural study using PatchDock showed that dihydromyricetin was docked in the active site pocket of dihydropyrimidinase, which was consistent with the findings from kinetic and fluorescence studies. This study was the first to demonstrate that naturally occurring product dihydromyricetin inhibited dihydropyrimidinase, even more than the substrate analogs (>3 orders of magnitude). These flavonols, particularly myricetin, may serve as drug leads and dirty drugs (for multiple targets) for designing compounds that target several cyclic amidohydrolases.


title: The papain-like protease of avian infectious bronchitis virus has deubiquitinating activity

text: Coronavirus papain-like proteases (PLPs) can act as proteases that process virus-encoded large replicase polyproteins and also as deubiquitinating (DUB) enzymes. Like the PLPs of other coronaviruses (CoVs), the avian infectious bronchitis virus (IBV) PLP catalyzes proteolysis of Gly-Gly dipeptide bonds to release mature cleavage products. However, the other functions of the IBV PLP are not well understood. In this study, we found that IBV exhibits strong global DUB activity with significant reductions of the levels of ubiquitin (Ub)-, K48-, and K63-conjugated proteins. The DUB activity exhibited a clear time dependence, with stronger DUB activity in the early stage of viral infection. Furthermore, the IBV replicase-encoded PLP, including the downstream transmembrane (TM) domain, is a DUB enzyme and dramatically reduced the level of Ub-conjugated proteins, while processing both K48- and K63-linked polyubiquitin chains. By contrast, PLP did not cause any reduction of haemagglutinin (HA)-Ub-conjugated proteins. In addition, mutations of the catalytic residues of PLP-TM, Cys1274Ser and His1437Lys, reduced DUB activity against Ub-, K48- and K63- conjugated proteins, indicating that the DUB activity of the PLP-TM wild-type protein is not completely dependent on its catalytic activity. Overall, these results demonstrate that the IBV-encoded PLP-TM functions as a DUB enzyme and suggest that IBV may interfere with the activation of host antiviral signaling pathway by degrading polyubiquitin-associated proteins.


Ventilation of COVID-19 patients in intensive care units


title: A Recombinant Fungal Lectin for Labeling Truncated Glycans on Human Cancer Cells

text: Cell surface glycoconjugates present alterations of their structures in chronic diseases and distinct oligosaccharide epitopes have been associated with cancer. Among them, truncated glycans present terminal non-reducing β-N-acetylglucosamine (GlcNAc) residues that are rare on healthy tissues. Lectins from unconventional sources such as fungi or algi provide novel markers that bind specifically to such epitopes, but their availability may be challenging. A GlcNAc-binding lectin from the fruiting body of the fungus Psathyrella velutina (PVL) has been produced in good yield in bacterial culture. A strong specificity for terminal GlcNAc residues was evidenced by glycan array. Affinity values obtained by microcalorimetry and surface plasmon resonance demonstrated a micromolar affinity for GlcNAcβ1-3Gal epitopes and for biantennary N-glycans with GlcNAcβ1-2Man capped branches. Crystal structure of PVL complexed with GlcNAcβ1-3Gal established the structural basis of the specificity. Labeling of several types of cancer cells and use of inhibitors of glycan metabolism indicated that rPVL binds to terminal GlcNAc but also to sialic acid (Neu5Ac). Analysis of glycosyltransferase expression confirmed the higher amount of GlcNAc present on cancer cells. rPVL binding is specific to cancer tissue and weak or no labeling is observed for healthy ones, except for stomach glands that present unique αGlcNAc-presenting mucins. In lung, breast and colon carcinomas, a clear delineation could be observed between cancer regions and surrounding healthy tissues. PVL is therefore a useful tool for labeling agalacto-glycans in cancer or other diseases.


THE “PERFECT CYTOKINE STORM” OF COVID-19


IUFoST/CIFST hold an Extraordinary Scientific Roundtable on COVID-19 and Food Safety


Is traditional Chinese medicine useful in the treatment of SARS?


title: Design of microarray probes for virus identification and detection of emerging viruses at the genus level

text: BACKGROUND: Most virus detection methods are geared towards the detection of specific single viruses or just a few known targets, and lack the capability to uncover the novel viruses that cause emerging viral infections. To address this issue, we developed a computational method that identifies the conserved viral sequences at the genus level for all viral genomes available in GenBank, and established a virus probe library. The virus probes are used not only to identify known viruses but also for discerning the genera of emerging or uncharacterized ones. RESULTS: Using the microarray approach, the identity of the virus in a test sample is determined by the signals of both genus and species-specific probes. The genera of emerging and uncharacterized viruses are determined based on hybridization of the viral sequences to the conserved probes for the existing viral genera. A detection and classification procedure to determine the identity of a virus directly from detection signals results in the rapid identification of the virus. CONCLUSION: We have demonstrated the validity and feasibility of the above strategy with a small number of viral samples. The probe design algorithm can be applied to any publicly available viral sequence database. The strategy of using separate genus and species probe sets enables the use of a straightforward virus identity calculation directly based on the hybridization signals. Our virus identification strategy has great potential in the diagnosis of viral infections. The virus genus and specific probe database and the associated summary tables are available at


title: Guillain‐Barré syndrome in a patient with antibodies against SARS‐COV‐2

text: There are now several reports on neurologic features of SARS‐CoV‐2 infection.(1 2) In a recent study of 214 patients with COVID‐19, 78 (36.4%) patients had neurological manifestations, including headache, dizziness, acute cerebrovascular diseases, and impaired consciousness.(2)


title: Demographics and economic burden of un-owned cats and dogs in the UK: results of a 2010 census

text: BACKGROUND: The population of dogs and cats passing through rescue shelters may be subject to compromised welfare and increased susceptibility to disease. Little information exists to describe this population, its dynamics and associated management practices. The aim of this study was to carry out a census of un-owned cats and dogs in the UK in 2010, and to document the origins, destinations, husbandry and costs associated with the care of these animals. RESULTS: A sampling frame was constructed by searching the databases of publicly registered charities for England, Scotland and Wales, registers of breed rescues, and by internet searches of animal welfare websites. Overall, 2,352 contacts for 1,380 organisations were identified. All were sent a postal questionnaire asking for data on the number of dogs and cats housed, their origins and eventual outcomes, and details of husbandry between January 1(st) and December 31(st) 2010. For those which were registered charities (595), financial records were also obtained. A response rate of 38.8% was obtained. Overall, in 2010, 89,571 dogs and 156,826 cats entered the care of the participating organisations. Approximately half of these animals were relinquished by their owners. Other origins included being found as strays or confiscated for welfare purposes. Seventy-five per cent of dogs and 77.1% of cats were rehomed. The next most common outcome was euthanasia, accounting for 10.4% of dogs and 13.2% cats. For dogs and cats, 44.3% and 62% of participants respectively reported having a waiting list, which frequently exceeded the actual capacity of the facility. Over 19,000 people were involved in the care of these animals, on a paid or voluntary basis. Financial records were available for 519/595 (87.2%) of the registered charities, and their total expenditure in 2010 was £340 million. CONCLUSIONS: This study showed that a large number of animals become un-owned each year, which could have considerable implications for their welfare. Despite the resources expended, demand still exceeds capacity for many organisations, and a substantial number of both cats and dogs are euthanased, suggesting that further understanding of how and why these animals become un-owned is essential in order to target interventions.


title: Chapter 9 Respiratory viral infections

text: Abstract Molecular analysis of respiratory viruses and the host response to both infection and vaccination have transformed our understanding of these ubiquitous pathogens. Polymerase chain reaction for the rapid and accurate diagnosis of viral infections has led to a better understanding of the epidemiology and impact of many common respiratory viruses and resulted in better patient care. Over the past decade a number of new respiratory viruses including human metapneumovirus and new coronaviruses have been discovered using molecular techniques such as random primer amplification, pan-viral array and next generation sequencing. Analysis of the host transcriptional response during respiratory viral infection using in-vitro, animal models and natural and experimental human challenge have furthered the understanding of the mechanisms and predictors of severe disease and may identify potential therapeutic targets to prevent and ameliorate illness.


title: COVID-19 as a Complex Intergovernmental Problem

text: Federations increasingly face complex policy challenges, from managing climate change to mass migration. COVID-19 is a prime example of this emerging type of problem. This research note introduces the concept of complex intergovernmental problems (CIPs) to better understand these types of challenges.


title: Comparative In Vivo Analysis of Recombinant Type II Feline Coronaviruses with Truncated and Completed ORF3 Region

text: Our previous in vitro comparative study on a feline coronavirus (FCoV) pair, differing only in the intactness of their ORF3abc regions, showed that the truncated ORF3abc plays an important role in the efficient macrophage/monocyte tropism of type II feline infectious peritonitis virus (FIPV). In the present study, we describe a challenge experiment with the same recombinant FCoVs in order to gain data on the in vivo characteristics on these viruses. While parent virus FIPV DF-2 developed feline infectious peritonitis in all the infected cats, its recombinant virus PBFIPV-DF-2, differing only in seven nucleotides, proved to be surprisingly low virulent, although caused an acute febrile episode similarly to the original FIPV DF-2. PBFIPV-DF-2 infection induced significantly lower virus neutralization titers than its parent virus, and lacked the second phase of viremia and development of fatal course of the disease. The recombinant PBFIPV-DF-2-R3i with completed ORF3abc gained biological properties that differentiate between the feline enteric coronavirus (FECV) and FIPV biotypes such as intensive replication in the gut, absence of viremia and weak or no serological response. Using reverse genetic approaches our study is the first experimental proof that ORF3abc is indeed responsible for the restriction of FECV replication to the intestine in vivo.


title: Estimating survival rates in MERS-CoV patients 14 and 45 days after experiencing symptoms and determining the differences in survival rates by demographic data, disease characteristics and regions: a worldwide study

text: Although Middle East respiratory syndrome coronavirus (MERS-CoV) has a recorded 5 years of circulation in 27 countries worldwide, there is no international study to assess whether there is variation in mortality by region. Neither has there been a comprehensive study detailing how the disease characteristics of MERS-CoV influence mortality in patients presenting symptoms. This study aimed to assess how region, patient and disease characteristics influence 14- and 45-day mortality in MERS patients. The author utilised publically available data on MERS-CoV. The study included 883 MERS patients reported between 5 January 2015 and 10 March 2017. Data on patient and disease characteristics were collected. The mean age at MERS-CoV diagnosis was 54.3 years: 69.1% were male, and 86.7% of the cases were reported from Saudi Arabia. About 40% of MERS patients studied were over the age of 60. The study estimated 14- and 45-day survival rates after initial onset of symptoms: 83.67% and 65.9%, respectively. Saudi Arabian MERS patients exhibited 4.1 and 5.0 times higher 14-day (adjusted hazard risk (aHR) = 4.1; 95% confidence interval (CI) 1.012–16.921) and 45-day (aHR = 5.0; 95% CI 1.856–13.581) mortality risk compared with MERS patients in the Republic of Korea or other countries. Similarly, Middle Eastern MERS patients showed 5.3 and 4.1 times higher 14-day (aHR = 5.3; 95% CI 1.070–25.902) and 45-day (aHR = 4.1; 95% CI 1.288–113.076) mortality risk compared with MERS patients in the Republic of Korea or other countries. The results demonstrated a link between mortality and geography, disease and patient factors such as regions, symptoms, source of infections, underlying medical conditions, modes of transmission, non-healthcare workers and those of older age. Educational programmes, access to healthcare and early diagnosis could be implemented as modifiable factors to reduce the higher mortality rates in MERS patients.


title: Remdesivir (GS-5734) Impedes Enterovirus Replication Through Viral RNA Synthesis Inhibition

text: Human enteroviruses are responsible for diverse diseases, from mild respiratory symptoms to fatal neurological complications. Currently, no registered antivirals have been approved for clinical therapy. Thus, a therapeutic agent for the enterovirus-related disease is urgently needed. Remdesivir (GS-5734) is a novel monophosphoramidate adenosine analog prodrug that exhibits potent antiviral activity against diverse RNA virus families, including positive-sense Coronaviridae and Flaviviridae and negative-sense Filoviridae, Paramyxoviridae, and Pneumoviridae. Currently, remdesivir is under phase 3 clinical development for disease COVID-19 treatment. Here, we found that remdesivir impeded both EV71 viral RNA (vRNA) and complementary (cRNA) synthesis, indicating that EV71 replication is inhibited by the triphosphate (TP) form of remdesivir. Moreover, remdesivir showed potent antiviral activity against diverse enteroviruses. These data extend the remdesivir antiviral activity to enteroviruses and indicate that remdesivir is a promising antiviral treatment for EV71 and other enterovirus infections.


COVID-19 and the role of neurosurgeons in Nepal


title: The impact of the COVID-19 pandemic on the provision of surgical care

text: The coronavirus disease 2019 (COVID-19) pandemic has brought about unprecedented adaptations in healthcare management, be it at a local or global level With so much that is not known about the disease itself, it has become manifestly clear that even less is known about how healthcare systems can contain such a disease In this situation we are obliged as clinicians and academics to share our experiences in order to pool together vital information that will not only help to tackle the matter at hand but will also serve as a road map for future crises such as this


title: Development of a real-time reverse-transcription-PCR method for detection of RD114 virus in canine vaccines

text: Abstract It is known that certain feline cell lines, such as the Crandell-Rees feline kidney cell, produce an RD-114-like virus. As a feline endogenous retrovirus, RD114 virus, exists in the genome of all cats, it can be assumed that contamination with the virus in feline and canine live vaccines manufactured by culturing cells of feline origin occurs. To detect an infectious RD114 virus in vitro, a LacZ marker rescue assay has recently been established. In feline and canine live vaccines approved in Japan, feline cell lines are widely used to produce vaccines, especially those containing canine parvovirus components. The LacZ marker rescue assay detects infectious viral particles, but the real-time reverse-transcription-PCR detects both infectious and defective viruses. The canine live vaccines manufactured in cells of feline origin showed positive results for the env gene by the real-time reverse-transcription-PCR, including all of the 8 vaccines produced in feline cell lines that were negative in the LacZ marker rescue assay. In conclusion, the present investigation suggests that the newly developed method has the advantages of shorter time requirements and can be applied as a valuable screening method to detect RD114 viral RNA in vaccines.


title: China's health transitions Bridie Andrews Medical Transi

text: Unknown


title: Discovery of novel virus sequences in an isolated and threatened bat species, the New Zealand lesser short-tailed bat (Mystacina tuberculata)

text: Bats harbour a diverse array of viruses, including significant human pathogens. Extensive metagenomic studies of material from bats, in particular guano, have revealed a large number of novel or divergent viral taxa that were previously unknown. New Zealand has only two extant indigenous terrestrial mammals, which are both bats, Mystacina tuberculata (the lesser short-tailed bat) and Chalinolobus tuberculatus (the long-tailed bat). Until the human introduction of exotic mammals, these species had been isolated from all other terrestrial mammals for over 1 million years (potentially over 16 million years for M. tuberculata). Four bat guano samples were collected from M. tuberculata roosts on the isolated offshore island of Whenua hou (Codfish Island) in New Zealand. Metagenomic analysis revealed that this species still hosts a plethora of divergent viruses. Whilst the majority of viruses detected were likely to be of dietary origin, some putative vertebrate virus sequences were identified. Papillomavirus, polyomavirus, calicivirus and hepevirus were found in the metagenomic data and subsequently confirmed using independent PCR assays and sequencing. The new hepevirus and calicivirus sequences may represent new genera within these viral families. Our findings may provide an insight into the origins of viral families, given their detection in an isolated host species.


title: RATE AND INFLUENCE OF RESPIRATORY VIRUS CO-INFECTION ON PANDEMIC (H1N1) INFLUENZA DISEASE

text: OBJECTIVES: Many patients with influenza have more than one viral agent with co-infection frequencies reported as high as 20%. The impact of respiratory virus copathogens on influenza disease is unclear. We sought to determine if respiratory virus co-infection with pandemic H1N1 altered clinical disease. METHODS: Respiratory samples from 229 and 267 patients identified with and without H1N1 influenza respectively were screened for the presence of 13 seasonal respiratory viruses by multiplex RT-PCR. Disease severity between coinfected and monoinfected H1N1 patients were quantified using a standardized clinical severity scale. Influenza viral load was calculated by quantitative RT-PCR. RESULTS: Thirty (13.1%) influenza samples screened positive for the presence of 31 viral copathogens. The most prominent copathogens included rhinovirus (61.3%), and coronaviruses (16.1%). Median clinical severity of both monoinfected and co-infected groups were 1. Patients coinfected with rhinovirus tended to have lower clinical severity (median 0), whereas non rhinovirus co-infections had substantially higher clinical severity (median 2). No difference in H1N1 viral load was observed between co-infected and mono infected groups. CONCLUSIONS: Respiratory viruses co-infect patients with influenza disease. Patients coinfected with rhinovirus had less severe disease while non-rhinovirus co-infections were associated with substantially higher severity without changes in influenza viral titer.


title: Rigorous Randomized Controlled Trial Implementation in the Era of COVID-19

text: Rigorous Randomized Controlled Trial Implementation in the Era of Novel Coronavirus Disease (COVID-19).


title: A Novel Therapeutic and Prophylactic Vaccine (HVJ-Envelope / Hsp65 DNA + IL-12 DNA) against Tuberculosis Using the Cynomolgus Monkey Model

text: Abstract We have developed a novel tuberculosis (TB) vaccine; a combination of the DNA vaccines expressing mycobacterial heat shock protein 65 (HSP65) and interleukin 12 (IL-12) delivered by the hemagglutinating virus of Japan (HVJ)-envelope and –liposome (HSP65 + IL-12/HVJ). An IL-12 expression vector (IL-12DNA) encoding single-chain IL-12 proteins comprised of p40 and p35 subunits were constructed. This vaccine provided remarkable protective efficacy in mouse and guinea pig models compared to the BCG vaccine on the basis of C.F.U of number of TB, survival, an induction of the CD8 positive CTL activity and improvement of the histopathological tuberculosis lesions. This vaccine also provided therapeutic efficacy against multi-drug resistant TB (MDR-TB) and extremely drug resistant TB (XDR-TB) (prolongation of survival time and the decrease in the number of TB in the lung) in murine models. Furthermore, we extended our studies to a cynomolgus monkey model, which is currently the best animal model of human tuberculosis. This novel vaccine provided a higher level of the protective efficacy than BCG based upon the assessment of mortality, the ESR, body weight, chest X-ray findings and immune responses. All monkeys in the control group (saline) died within 8 months, while 50% of monkeys in the HSP65+hIL-12/HVJ group survived more than 14 months post-infection (the termination period of the experiment). Furthermore, the BCG priming and HSP65 + IL-12/HVJ vaccine (booster) by the priming-booster method showed a synergistic effect in the TB-infected cynomolgus monkey (100% survival). In contrast, 33% of monkeys from BCG Tokyo alone group were alive (33% survival). Furthermore, this vaccine exerted therapeutic efficacy (100% survival) and augmentation of immune responses in the TB-infected monkeys. These data indicate that our novel DNA vaccine might be useful against Mycobacterium tuberculosis including XDR-TB and MDR-TB for human therapeutic clinical trials.


title: The Concept of Making On-Chip Thermal Cycler for RT-PCR Using Conjugate Heat Transfer in Diverging Microchannel

text: Covid-19 is pandemic to which the world is fighting. Various precautionary measures are being imposed all over the world which is affecting the routine life of an individual and also the economy worldwide. Although, a definite vaccine is still not known to medical science but they are able to distinguish Covid-19 from the other types of flu. Presently this is being done by detecting the SARS-CoV-2 virus using RT-PCR technique as recommended by the World Health Organization (WHO) (WHO, Geneva, 2020). Reverse Transcription Polymerase Chain Reaction (RT-PCR) is a nucleic acid amplification test that converts the RNA into DNA and subsequently amplifies the specific DNA targets. This method was already being employed to detect the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) (Emery et al. in Emerg Infect Dis 10(2):311, 2004). The entire process of DNA amplification takes place in three steps: denaturation, annealing, and extension for which the sample is required to be maintained at constant temperatures of 95, 55 and 72 °C, respectively. This article introduces the technology to achieve a constant temperature which can be tweaked to develop on-chip RT-PCR.


title: Influenza vaccination in the COVID-19 era

text: Abstract Influenza spreads globally annually with significant paediatric and adult attack rates and considerable morbidity, mortality and the exacerbation of extant chronic disease. In the northern and southern hemispheres, outbreaks occur mainly in the respective winter seasons. Influenza vaccination is available but only partially effective. In the absence of a vaccine, in winter, novel coronavirus COVID-19 will also circulate in parallel with seasonal influenza. Thus far it appears that with the current strains of these two viruses, the clinical outcome of co-infection is not significantly worse than infection with COVID-19 alone. However, several strains of influenza circulate, including strains still to come. Similarly, COVID-19 has several strains, with probably more to come. This paper discusses these issues and estimates ideal minimum influenza vaccination coverage based on an estimated influenza Basic Reproduction Number (R0) of 0.9–2.1 so as to obtain herd immunity or approach it. There is a strong argument for attempting near universal population coverage with the annual influenza vaccine leading up to next winter.


title: Are we fully exploiting type I Interferons in today's fight against COVID-19 pandemic?

text: Coronavirus disease 2019 (COVID-19) first emerged in late 2019 in China. At the time of writing, its causative agent SARS-CoV-2 has spread worldwide infecting over 9 million individuals and causing more than 460,000 deaths. In the absence of vaccines, we are facing the dramatic challenge of controlling COVID-19 pandemic. Among currently available drugs, type I Interferons (IFN-I) – mainly IFN-α and β –represent ideal candidates given their direct and immune-mediated antiviral effects and the long record of clinical use. However, the best modalities of using these cytokines in SARS-CoV-2 infected patients is a matter of debate. Here, we discuss how we can exploit the current knowledge on IFN-I system to tailor the most promising dosing, timing and route of administration of IFN-I to the disease stage, with the final aim of making these cytokines a valuable therapeutic strategy in today's fight against COVID-19 pandemic.


title: Porcine reproductive and respiratory syndrome virus nucleocapsid protein modulates interferon-β production by inhibiting IRF3 activation in immortalized porcine alveolar macrophages

text: Porcine reproductive and respiratory syndrome virus (PRRSV) infection appears to elicit a weak innate immune response suppressing type 1 interferon (IFN) production. Recent studies have revealed that several nonstructural proteins encoded by the PRRSV genome independently antagonize the type 1 IFN system. The present study sought to identify the structural proteins that possess the immune evasion properties in immortalized porcine alveolar macrophages (PAM). Each structural protein gene was stably expressed in a porcine monocyte-derived macrophage cell line, PAM-pCD163, and tested for its potential to inhibit IFN-β induction. We then focused on the nucleocapsid (N) protein, which has a strong inhibitory effect on dsRNA-induced IFN-β production. Upon dsRNA stimulation, IFN-β production was shown to decrease proportionally with increasing levels of N expression. Furthermore, the PRRSV N protein was found to down-regulate IFN-dependent gene production by dsRNA. Taken together, these results indicate the ability of N to modulate the dsRNA-mediated IFN induction pathways. In addition, the N protein significantly interfered with dsRNA-induced phosphorylation and nuclear translocation of IRF3. Our data suggest that the PRRSV N protein is a responsible component, independent of other nonstructural elements, for evading the IFN response by antagonizing IRF3 activation.


title: Promoting Functional Communication Within the Home

text: Functional communication skills are essential for all learners and must be promoted within all environments, including the home. During this time of home confinement, many families will need to look at opportunities for their children to use existing functional communication skills or even to acquire new skills. This article describes a set of 9 critical communication skills and provides a variety of examples of how families can improve the use of these important skills. Some of these involve speaker (expressive) skills, whereas others involve listener (receptive) skills.


title: ERAD and how viruses exploit it

text: Endoplasmic reticulum (ER)-associated degradation (ERAD) is a universally important process among eukaryotic cells. ERAD is necessary to preserve cell integrity since the accumulation of defective proteins results in diseases associated with neurological dysfunction, cancer, and infections. This process involves recognition of misfolded or misassembled proteins that have been translated in association with ER membranes. Recognition of ERAD substrates leads to their extraction through the ER membrane (retrotranslocation or dislocation), ubiquitination, and destruction by cytosolic proteasomes. This review focuses on ERAD and its components as well as how viruses use this process to promote their replication and to avoid the immune response.


title: Avian Influenza Virus Infections in Humans

text: Seroepidemiologic and virologic studies since 1889 suggested that human influenza pandemics were caused by H1, H2, and H3 subtypes of influenza A viruses. If not for the 1997 avian A/H5N1 outbreak in Hong Kong of China, subtype H2 is the likely candidate for the next pandemic. However, unlike previous poultry outbreaks of highly pathogenic avian influenza due to H5 that were controlled by depopulation with or without vaccination, the presently circulating A/H5N1 genotype Z virus has since been spreading from Southern China to other parts of the world. Migratory birds and, less likely, bird trafficking are believed to be globalizing the avian influenza A/H5N1 epidemic in poultry. More than 200 human cases of avian influenza virus infection due to A/H5, A/H7, and A/H9 subtypes mainly as a result of poultry-to-human transmission have been reported with a > 50% case fatality rate for A/H5N1 infections. A mutant or reassortant virus capable of efficient human-to-human transmission could trigger another influenza pandemic. The recent isolation of this virus in extrapulmonary sites of human diseases suggests that the high fatality of this infection may be more than just the result of a cytokine storm triggered by the pulmonary disease. The emergence of resistance to adamantanes (amantadine and rimantadine) and recently oseltamivir while H5N1 vaccines are still at the developmental stage of phase I clinical trial are causes for grave concern. Moreover, the to-be pandemic strain may have little cross immunogenicity to the presently tested vaccine strain. The relative importance and usefulness of airborne, droplet, or contact precautions in infection control are still uncertain. Laboratory-acquired avian influenza H7N7 has been reported, and the laboratory strains of human influenza H2N2 could also be the cause of another pandemic. The control of this impending disaster requires more research in addition to national and international preparedness at various levels. The epidemiology, virology, clinical features, laboratory diagnosis, management, and hospital infection control measures are reviewed from a clinical perspective.


title: Simultaneous removal of bioaerosols, odors and volatile organic compounds from a wastewater treatment plant by a full-scale integrated reactor

text: Biological control of odors and bioaerosols in wastewater treatment plants (WWTPs) have gained more attention in recent years. The simultaneous removal of odors, volatile organic compounds (VOCs) and bioaerosols in each unit of a full-scale integrated-reactor (FIR) in a sludge dewatering room was investigated. The average removal efficiencies (REs) of odors, VOCs and bioaerosols were recorded as 98.5%, 25 94.7% and 86.4%, respectively, at an inlet flow rate of 5760 m(3)/h. The RE of each unit decreased, and the activated carbon adsorption zone (AZ) played a more important role as the inlet flow rate increased. The REs of hydrophilic compounds were higher than those of hydrophobic compounds. For bioaerosols, roughly 35% of airborne heterotrophic bacteria (HB) was removed in the low-pH zone (LPZ) while over 30% of total fungi (TF) was removed in the neutral-pH zone (NPZ). Most bioaerosols removed by the biofilter (BF) had a particle size larger than 4.7 μm while bioaerosols with small particle size were apt to be adsorbed by AZ. The microbial community in the BF changed significantly at different units. Health risks were found to be associated with H(2)S rather than with bioaerosols at the FIR outlet.


title: Canine adipose tissue-derived mesenchymal stem cells pre-treated with TNF-alpha enhance immunomodulatory effects in inflammatory bowel disease in mice

text: Abstract Canine inflammatory bowel disease (IBD) is an intractable autoimmune disorder that results in various gastrointestinal and systemic symptoms. Mesenchymal stem cells (MSCs), which release immunomodulatory factors such as tumor necrosis factor-α (TNF-α)-induced gene/protein 6 (TSG-6) and prostaglandin E2 (PGE2), have been suggested as an alternative therapeutic option for IBD treatment in veterinary medicine. Furthermore, although it is known that MSCs pre-treated with pro-inflammatory cytokines show enhanced anti-inflammatory properties via the secretion of soluble factors, the underlying mechanisms of IBD remain unclear. The aim of this study was to demonstrate the therapeutic effects and corresponding mechanisms of canine adipose tissue-derived (cAT)-MSCs stimulated with TNF-α in mouse models of IBD. Mice with dextran sulfate sodium (DSS)- or dinitrobenzene sulfonic acid (DNBS)-induced colitis were injected intraperitoneally with cAT-MSCs pre-treated with TNF-α. Colitis severity was assessed and colon tissues were collected for histopathological, enzyme-linked immunosorbent assay, and flow cytometry analysis. cAT-MSCs stimulated with TNF-α secreted higher concentrations of immunomodulatory factors such as TSG-6 and PGE2, which play a key role in inducing phenotypic alterations in macrophages. Consequently, TNF-α-pre-treated cAT-MSCs further regulated colonic inflammatory cytokines such as interleukin (IL)-1β, IL-6, and IL-10, and ameliorated DSS- or DNBS-induced colitis in mice. Additionally, we demonstrated that M1 macrophages (F4/80+/iNOS+ cells) were decreased in colon tissues from mice treated with TNF-α-pre-treated cAT-MSCs, whereas M2 macrophages (F4/80+/CD206+ cells) were increased. These results may suggest a new cell-based therapeutic option for treating IBD.


title: Porcine epidemic diarrhea virus (PEDV): An update on etiology, transmission, pathogenesis, and prevention and control

text: Porcine epidemic diarrhea virus (PEDV), a member of the genus Alphacoronavirus in the family Coronaviridae, causes acute diarrhea and/or vomiting, dehydration and high mortality in neonatal piglets. Two different genogroups of PEDV, S INDEL [PEDV variant containing multiple deletions and insertions in the S1 subunit of the spike (S) protein, G1b] and non-S INDEL (G2b) strains were detected during the diarrheal disease outbreak in US swine in 2013-2014. Similar viruses are also circulating globally. Continuous improvement and update of biosecurity and vaccine strains and protocols are still needed to control and prevent PEDV infections worldwide. Although the non-S INDEL PEDV was highly virulent and the S INDEL PEDV caused milder disease, the latter has the capacity to cause illness in a high number of piglets on farms with low biosecurity and herd immunity. The main PEDV transmission route is fecal–oral, but airborne transmission via the fecal–nasal route may play a role in pig-to-pig and farm-to-farm spread. PEDV infection of neonatal pigs causes fecal virus shedding (alongside frequent detection of PEDV RNA in the nasal cavity), acute viremia, severe atrophic enteritis (mainly jejunum and ileum), and increased pro-inflammatory and innate immune responses. PEDV-specific IgA effector and memory B cells in orally primed sows play a critical role in sow lactogenic immunity and passive protection of piglets. This review focuses on the etiology, transmission, pathogenesis, and prevention and control of PEDV infection.


title: Koch's Postulates and the Pathogenesis of Comparative Infectious Disease Causation Associated with Bartonella species

text: Summary In his homage to Lucretius (‘Georgica’), Vergil is credited with stating: ‘Felix qui potuit rerum cognoscere causas’ (‘Fortunate is he who knows the causes of things’). Based on numerous commentaries and publications it is obvious that clinicians, diagnosticians and biomedical research scientists continue to struggle with disease causation, particularly in the assessment of the pathogenic role of ‘stealth pathogens’ that produce persistent infections in the host. Bartonella species, because of their evolutionary ability to induce persistent intravascular infections, present substantial challenges for researchers attempting to clarify the ability of these stealth bacteria to cause disease. By studying the comparative biological and pathological behaviour of microbes across mammalian genera, researchers might be able more rapidly to advance medical science and, subsequently, patient care by undertaking focused research efforts involving a single mammalian species or by attempting to recapitulate a complex disease in an rodent model. Therefore, in an effort to further assist in the establishment of disease causation by stealth pathogens, we use recent research observations involving the genus Bartonella to propose an additional postulate of comparative infectious disease causation to Koch's postulates.


title: National French survey of COVID-19 symptoms in people aged 70 and over

text: The objective of this national French survey was to determine the COVID-19 semiology in seniors(n=353; mean,84.7±7.0y). 57.8% of patients exhibited ≤3symptoms, including thermal dysregulation(83.6%), cough(58.9%), asthenia(52.7%), polypnea(39.9%), gastrointestinal signs(24.4%). Patients≥80y exhibited falls(P=0.002) and asthenia(P=0.002). Patients with neurocognitive disorders exhibited delirium(P<0.001) and altered consciousness(P=0.001). Clinical peculiarities of COVID-19 were reported in seniors.


Companies partner to develop PPE for frontline health care workers


title: Fate of Manure‐Borne Pathogens during Anaerobic Digestion and Solids Separation

text: Anaerobic digestion can inactivate zoonotic pathogens present in cattle manure, which reduces transmission of these pathogens from farms to humans through the environment. However, the variability of inactivation across farms and over time is unknown because most studies have examined pathogen inactivation under ideal laboratory conditions or have focused on only one or two full‐scale digesters at a time. In contrast, we sampled seven full‐scale digesters treating cattle manure in Wisconsin for 9 mo on a biweekly basis (n = 118 pairs of influent and effluent samples) and used real‐time quantitative polymerase chain reaction to analyze these samples for 19 different microbial genetic markers. Overall, inactivation of pathogens and fecal indicators was highly variable. When aggregated across digester and season, log‐removal values for several representative microorganisms—bovine Bacteroides, Bacteroidales‐like CowM3, and bovine polyomavirus—were 0.78 ± 0.34, 0.70 ± 0.50, and 0.53 ± 0.58, respectively (mean ± SD). These log‐removal values were up to two times lower than expected based on the scientific literature. Thus, our study indicates that full‐scale anaerobic digestion of cattle manure requires optimization with regard to pathogen inactivation. Future studies should focus on identifying the potential causes of this suboptimal performance (e.g., overloading, poor mixing, poor temperature control). Our study also examined the fate of pathogens during manure separation and found that the majority of microbes we detected ended up in the liquid fraction of separated manure. This finding has important implications for the transmission of zoonotic pathogens through the environment to humans. CORE IDEAS: Pathogen inactivation is highly variable among full‐scale anaerobic digesters. Pathogen inactivation by full‐scale digesters on cattle farms needs optimization. Most microbes end up in the liquid fraction during solids separation of manure.


title: Clinical Utility of Buccal Swabs for Severe Acute Respiratory Syndrome Coronavirus 2 Detection in Coronavirus Disease 2019–Infected Children

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected from at least 1 buccal specimen in 9 of 11 coronavirus disease 2019 (COVID-19)–infected children (81.8%). Viral loads in buccal specimens were substantially lower than those in nasopharyngeal specimens. Buccal swabs are not good as COVID-19 screening specimens in children.


title: Ventilator Triage Policies During the COVID-19 Pandemic at U.S. Hospitals Associated With Members of the Association of Bioethics Program Directors

text: BACKGROUND: The coronavirus disease 2019 pandemic has or threatens to overwhelm health care systems. Many institutions are developing ventilator triage policies. OBJECTIVE: To characterize the development of ventilator triage policies and compare policy content. DESIGN: Survey and mixed-methods content analysis. SETTING: North American hospitals associated with members of the Association of Bioethics Program Directors. PARTICIPANTS: Program directors. MEASUREMENTS: Characteristics of institutions and policies, including triage criteria and triage committee membership. RESULTS: Sixty-seven program directors responded (response rate, 91.8%); 36 (53.7%) hospitals did not yet have a policy, and 7 (10.4%) hospitals' policies could not be shared. The 29 institutions providing policies were relatively evenly distributed among the 4 U.S. geographic regions (range, 5 to 9 policies per region). Among the 26 unique policies analyzed, 3 (11.3%) were produced by state health departments. The most frequently cited triage criteria were benefit (25 policies [96.2%]), need (14 [53.8%]), age (13 [50.0%]), conservation of resources (10 [38.5%]), and lottery (9 [34.6%]). Twenty-one (80.8%) policies use scoring systems, and 20 of these (95.2%) use a version of the Sequential Organ Failure Assessment score. Among the policies that specify the triage team's composition (23 [88.5%]), all require or recommend a physician member, 20 (87.0%) a nurse, 16 (69.6%) an ethicist, 8 (34.8%) a chaplain, and 8 (34.8%) a respiratory therapist. Thirteen (50.0% of all policies) require or recommend those making triage decisions not be involved in direct patient care, but only 2 (7.7%) require that their decisions be blinded to ethically irrelevant considerations. LIMITATION: The results may not be generalizable to institutions without academic bioethics programs. CONCLUSION: Over one half of respondents did not have ventilator triage policies. Policies have substantial heterogeneity, and many omit guidance on fair implementation.


title: COVID‐19 and thalassaemia: A position statement of the Thalassaemia International Federation

text: OBJECTIVES: Many patients with haemoglobinopathies, including thalassaemia and sickle cell disease, are at increased risk of developing severe complications from the coronavirus disease 2019 (COVID‐19). Although epidemiologic evidence concerning the novel coronavirus (SARS‐CoV‐2) infection in these patients is currently lacking, the COVID‐19 pandemic represents a significant challenge for haemoglobinopathy patients, their families and their attending physicians. METHODS: The present statement summarizes the key challenges concerning the management of haemoglobinopathies, with particular focus on patients with either transfusion‐dependent or non‐transfusion‐dependent thalassaemia, identifies the gaps in knowledge and suggests measures and strategies to deal with the pandemic, based on available evidence and expert opinions. Key areas covered include patients’ risk level, adaptation of haemoglobinopathy care, safety of blood transfusions, blood supply challenges, and lifestyle and nutritional considerations. CONCLUSIONS: The proposed measures and strategies may be useful as a blueprint for other disorders which require regular hospital visits, as well as for the timely adaptation of patient care during similar future pandemics.


Age-related difference in the rate of COVID-19 mortality in women versus men


title: The Relationship between Diabetes Mellitus and COVID-19 Prognosis: A Retrospective Cohort Study in Wuhan, China

text: BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease, first appeared in Wuhan, China, and quickly spread throughout the world. We aimed to understand the relationship between diabetes mellitus and the prognosis of COVID-19. METHODS: Demographic, clinical, laboratory, radiologic, treatments, complications, and clinical outcomes data were extracted from electronic medical records and compared between diabetes (n=84) and non-diabetes (n=500) groups. Kaplan-Meier method and multivariate Cox analysis were applied to determine the risk factors for the prognosis of COVID-19. RESULTS: Compared to non-diabetic patients, diabetic patients had higher levels of neutrophils (p = 0.014), c-reactive protein (p = 0.008), procalcitonin (p < 0.01), and D-dimer (p = 0.033), and lower levels of lymphocytes (p = 0.032) and albumin (p = 0.035). Furthermore, diabetic patients had a significant higher incidence of bilateral pneumonia (86.9%, p = 0.020). In terms of complications and clinical outcomes, the incidence of respiratory failure (36.9% vs. 24.2%, p = 0.022), acute cardiac injury (47.4% vs. 21.2%, p < 0.01) and death (20.2% vs. 8.0%, p = 0.001) in the diabetes group was significantly higher than that in non-diabetes group. Kaplan-Meier survival curve showed that COVID-19 patients with diabetes had a shorter overall survival time. Multivariate Cox analysis indicated that diabetes (HR 2.180, p = 0.031) was an independent risk factor for COVID-19 prognosis. In subgroup analysis, we divided diabetic patients into insulin required and non-insulin required groups according to whether they needed insulin, and found that diabetic patients requiring insulin may have a higher risk of disease progression and worse prognosis after the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). CONCLUSIONS: Diabetes is an independent risk factor for the prognosis of COVID-19. More attention should be paid to the prevention and treatment for diabetic patients, especially those who require insulin therapy.


title: Constitutive expression of types 1 and 2 cytokines by alveolar macrophages from feline immunodeficiency virus-infected cats

text: Abstract Evidence suggests that feline immunodeficiency virus (FIV), causes pulmonary immunodeficiency. The overall objective of this study was to explore FIV-induced alterations in cell counts and cytokine gene expression in the pulmonary compartment during the acute stage infection. Bronchoalveolar lavage (BAL) cells were collected from FIV-infected and control cats at 0, 4, 10, and 16 weeks post-FIV infection for phenotype and cytokine analysis. The major change in BAL cellular populations following FIV-infection was the development of a neutrophilia. Total BAL cell counts and relative numbers of alveolar macrophages (AM), eosinophils, and lymphocytes remained similar in both groups. The RT-qcPCR analyses of AM purified from BAL showed constitutive expression of TNFα, IL6 and IL10 mRNAs that peaked during the acute stage of infection then declined. The TNFα and IL6 bioactive protein secretion showed a similar response. In contrast, IFNγ expression increased progressively with time after infection and paralleled a progressive increase in FIV-gag mRNA in AM. The IL12 p40 expression also differed from the other cytokines in that there was a progressive decrease in the number of cats with AM IL12 expression following FIV infection. Infection of AM in vitro with FIV also caused an increase in TNFα and IL6 mRNA and bioactive protein suggesting that the increased cytokine response by AM following infection of cats with FIV is an intrinsic characteristic of FIV-infected AM. In summary, pulmonary immune changes seen in FIV-infected cats are similar to those seen in HIV-infected human patients.


title: Rhinitis and Meningitis in Two Shelter Cats Caused by Streptococcus equi subspecies zooepidemicus

text: Summary In the past 6 years there have been increasing reports describing outbreaks of a severe fatal respiratory disease associated with Streptococcus equi subspecies zooepidemicus (SEZ) in dogs maintained in shelters, research facilities and kennels. Although SEZ appears to be an emerging pathogen of dogs kept in intensively housed environments, this bacterium has not been reported as a cause of death in intensively housed cats. This report describes fatal SEZ infection in two adult cats housed in separate animal shelter facilities. Both cats had acute onset of illness, which progressed to death in less than 24h. Post-mortem examination revealed rhinitis and meningitis and SEZ was demonstrated in the nasal cavity and brain. Polymerase chain reaction and sequence analysis of a 500 base pair region of the 16S rRNA gene confirmed the identity of the bacterium.


title: No evidence for distinct types in the evolution of SARS-CoV-2

text: A recent study by Tang et al. (2020) claimed that two major types of SARS-CoV-2 had evolved in the ongoing COVID-19 pandemic and that one of these types was more “aggressive” than the other. Given the repercussions of these claims and the intense media coverage of these types of articles, we have examined in detail the data presented by Tang et al, and show that the major conclusions of that paper cannot be substantiated. Using examples from other viral outbreaks we discuss the difficulty in demonstrating the existence or nature of a functional effect of a viral mutation, and we advise against overinterpretation of genomic data during the pandemic.


title: Clinical picture, diagnosis, treatment and outcome of severe acute respiratory syndrome (SARS) in children

text: Summary Children are susceptible to infection by SARS-associated coronavirus (SARS-CoV) but the clinical picture of SARS is milder than in adults. Teenagers resemble adults in presentation and disease progression and may develop severe illness requiring intensive care and assisted ventilation. Fever, malaise, cough, coryza, chills or rigor, sputum production, headache, myalgia, leucopaenia, lymphopaenia, thrombocytopaenia, mildly prolonged activated partial thromboplastin times and elevated lactate dehydrogenase levels are common presenting features. Radiographic findings are non-specific but high-resolution computed tomography of the thorax in clinically suspected cases may be an early diagnostic aid when initial chest radiographs appear normal. The improved reverse transcription-polymerase chain reaction (RT-PCR) assays are critical in the early diagnosis of SARS, with sensitivity approaching 80% in the first 3 days of illness when performed on nasopharyngeal aspirates, the preferred specimens. Absence of seroconversion to SARS-CoV beyond 28 days from disease onset generally excludes the diagnosis. The best treatment strategy for SARS among children remains to be determined. No case fatality has been reported in children and the short- to medium-term outcome appears to be good. The importance of continued monitoring for any long-term complications due to the disease or its empiric treatment, cannot be overemphasised.


title: Kawasaki Disease Features and Myocarditis in a Patient with COVID-19

text: A 10-year-old male with prolonged fever, rash, and conjunctivitis presented to the emergency department with concern for Kawasaki disease, found to have myocarditis and PCR positive for SARS-CoV-2. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00246-020-02393-0) contains supplementary material, which is available to authorized users.


title: Clinical Features Predicting Mortality Risk in Patients With Viral Pneumonia: The MuLBSTA Score

text: OBJECTIVE: The aim of this study was to further clarify clinical characteristics and predict mortality risk among patients with viral pneumonia. METHODS: A total of 528 patients with viral pneumonia at RuiJin hospital in Shanghai from May 2015 to May 2019 were recruited. Multiplex real-time RT-PCR was used to detect respiratory viruses. Demographic information, comorbidities, routine laboratory examinations, immunological indexes, etiological detections, radiological images and treatment were collected on admission. RESULTS: 76 (14.4%) patients died within 90 days in hospital. A predictive MuLBSTA score was calculated on the basis of a multivariate logistic regression model in order to predict mortality with a weighted score that included multilobular infiltrates (OR = 5.20, 95% CI 1.41–12.52, p = 0.010; 5 points), lymphocyte ≤ 0.8(∗)10(9)/L (OR = 4.53, 95% CI 2.55–8.05, p < 0.001; 4 points), bacterial coinfection (OR = 3.71, 95% CI 2.11–6.51, p < 0.001; 4 points), acute-smoker (OR = 3.19, 95% CI 1.34–6.26, p = 0.001; 3 points), quit-smoker (OR = 2.18, 95% CI 0.99–4.82, p = 0.054; 2 points), hypertension (OR = 2.39, 95% CI 1.55–4.26, p = 0.003; 2 points) and age ≥60 years (OR = 2.14, 95% CI 1.04–4.39, p = 0.038; 2 points). 12 points was used as a cut-off value for mortality risk stratification. This model showed sensitivity of 0.776, specificity of 0.778 and a better predictive ability than CURB-65 (AUROC = 0.773 vs. 0.717, p < 0.001). CONCLUSION: Here, we designed an easy-to-use clinically predictive tool for assessing 90-day mortality risk of viral pneumonia. It can accurately stratify hospitalized patients with viral pneumonia into relevant risk categories and could provide guidance to make further clinical decisions.


title: COVID19 and acute lymphoblastic leukemias of children and adolescents: first recommendations of the Leukemia committee of the French Society for the fight against Cancers and Leukemias in children and adolescents (SFCE)

text: Abstract Since the emergence of the SARS-CoV-2infection, many recommendations have been made. However, the very nature of acute lymphoblastic leukemias and their treatment in children and adolescents led the Leukemia Committee of the French Society for the fight against Cancers and leukemias in children and adolescents (SFCE) to propose more specific recommendations, even if data for this population are still scarce. They may have to evolve according to the rapid evolution of knowledge on COVID19.


title: A recombinant subunit vaccine formulation protects against lethal Nipah virus challenge in cats

text: Abstract Nipah virus (NiV) and Hendra virus (HeV) are closely related deadly zoonotic paramyxoviruses that have emerged and re-emerged over the last 10 years. In this study, a subunit vaccine formulation containing only recombinant, soluble, attachment glycoprotein from HeV (sGHeV) and CpG adjuvant was evaluated as a potential NiV vaccine in the cat model. Different amounts of sGHeV were employed and sG-induced immunity was examined. Vaccinated animals demonstrated varying levels of NiV-specific Ig systemically and importantly, all vaccinated cats possessed antigen-specific IgA on the mucosa. Upon oronasal challenge with NiV (50,000TCID50), all vaccinated animals were protected from disease although virus was detected on day 21 post-challenge in one animal. The ability to elicit protective systemic and mucosal immunity in this animal model provides significant progress towards the development of a human subunit vaccine against henipaviruses.


title: Bismuth Complexes Inhibit the SARS Coronavirus

text: Hold tight: Bismuth complexes including ranitidine bismuth citrate effectively inhibit the nucleoside triphosphate hydrolase and DNA unwinding activities of the SARS coronavirus (SCV) helicase and dramatically reduce SCV replication levels in infected cells. This suggests that bismuth‐based drugs should be further evaluated for the treatment of SCV infections in vivo. ss=single‐stranded DNA, ds=duplex DNA.[Image: see text]


Chicken soup in the time of COVID


title: Enhancement of ribosomal frameshifting by oligonucleotides targeted to the HIV gag-pol region.

text: The pol gene of all retroviruses is expressed as a gag-pol fusion protein which is proteolytically processed to produce all viral enzymes. In the human immunodeficiency virus (HIV), the gag and pol genes overlap by 241 nucleotides with pol in the -1 phase with respect to gag. The gag-pol fusion is produced via a -1 ribosomal frameshifting event that brings the overlapping, out-of-phase gag and pol genes into translational phase. Frameshifting occurs at a so called 'shift site' 8-10 nucleotides upstream of a hairpin loop which may play a role in the regulation of frameshifting. We have fused this region of HIV-1 to the 5' end of the firefly luciferase reporter gene in order to quantitatively measure ribosomal frameshifting both in cells and by in vitro translation. A series of 2'-O-methyl oligonucleotides was designed to specifically bind the sequences which flank the gag-pol hairpin. Ribosomal frameshifting is enhanced up to 6 fold by those oligonucleotides which bind the area just 3 to the stem. Oligonucleotides which bind 5' to the stem have no effect on frameshift efficiency. In addition, we have constructed a series of fusion genes which mimic the effect of the bound oligonucleotides with intramolecular hairpins. The results suggest that increasing RNA secondary structure downstream of the shift site increases the frequency of ribosomal frameshifting, and that this effect can be mimicked by antisense oligonucleotides.


Challenges of methadone maintenance treatment during the COVID-19 epidemic in China: policy and service recommendations


title: Overview of Microarray Analysis of Gene Expression and its Applications to Cervical Cancer Investigation

text: SUMMARY Cervical cancer is one of the leading female cancers in Taiwan and ranks as the fifth cause of cancer death in the female population. Human papillomavirus has been established as the causative agent for cervical neoplasia and cervical cancer. However, the tumor biology involved in the prognoses of different cell types in early cancers and tumor responses to radiation in advanced cancers remain largely unknown. The introduction of microarray technologies in the 1990s has provided genome-wide strategies for searching tens of thousands of genes simultaneously. In this review, we first summarize the two types of microarrays: oligonucleotides microarray and cDNA microarray. Then, we review the studies of functional genomics in cervical cancer. Gene expression studies that involved cervical cancer cell lines, cervical cells of cancer versus normal ectocervix, cancer tissues of different histology, radioresistant versus radiosensitive patients, and the combinatorial gene expression associated with chromosomal amplifications are discussed. In particular, CEACAM5, TACSTD1, S100P, and MSLN have shown to be upregulated in adenocarcinoma, and increased expression levels of CEACAM5 and TACSTD1 were significantly correlated with poorer patient outcomes. On the other hand, 35 genes, including apoptotic genes (e.g. BIK, TEGT, SSI-3), hypoxia-inducible genes (e.g. HIF1A, CA12), and tumor cell invasion and metastasis genes (e.g. CTSL, CTSB, PLAU, CD44), have been noted to echo the hypothesis that increased tumor hypoxia leads to radiation resistance in cervical cancer during radiation.


title: Synthesis and evaluation of phenylisoserine derivatives for the SARS-CoV 3CL protease inhibitor

text: Abstract Synthesis and evaluation of new scaffold phenylisoserine derivatives connected with the essential functional groups against SARS CoV 3CL protease are described. The phenylisoserine backbone was found by simulation on GOLD software and the structure activity relationship study of phenylisoserine derivatives gave SK80 with an IC50 value of 43μM against SARS CoV 3CL R188I mutant protease.


title: CD13/aminopeptidase N and murine cytomegalovirus infection

text: Abstract CD13/aminopeptidase N is a membrane-bound metalloproteinase implicated in human cytomegalovirus (HCMV) infection and pathogenesis. Anti-CD13 antibodies can neutralize HCMV infectivity, and HCMV viremia after bone marrow transplantation induces anti-CD13 autoantibodies which correlate with development of chronic graft vs. host disease. We examined whether murine CD13/APN was similarly implicated in murine cytomegalovirus (MCMV) disease. MCMV infection did induce anti-CD13 antibodies in mice in a strain-specific manner. ICR and 129S mice developed high titers of anti-CD13 antibodies and anti-MCMV antibodies after MCMV infection, whereas CBA and CBAxC57BL/6 f1 hybrid mice produced antibodies against MCMV only. Unlike HCMV, no evidence was found for a correlation between host cell CD13/APN expression and infection, or for the presence of CD13/APN on MCMV particles, although APN inhibitors decreased MCMV plaque formation. Reproduction of CD13/APN autoantibody production in the murine system should make it possible to determine if these antibodies contribute to CMV pathogenesis.


title: Seventy-two-hour emergency department revisits among adults with chronic diseases: a Saudi Arabian study

text: BACKGROUND: Despite the increase in adult emergency department (ED) utilization in Saudi Arabia, no studies have evaluated the 72-hour revisits. This study estimates the rate of 72-hour ED revisits and identifies its reasons and predictive factors among adults with chronic diseases. PATIENTS AND METHODS: A hospital-based retrospective study that included 24,206 ED discharges for adults with chronic diseases at the adult ED of King Abdulaziz Medical City, Riyadh between September 13, 2015 and July 29, 2017 was performed. We extracted data on demographic information, reasons for ED visits/revisits, health insurance coverage, weekend ED arrival, and mortality. RESULTS: A sample of 24,206 ED discharges for 19,697 adults with at least one chronic disease was included in the analysis. The rate of 72-hour revisits in this study population was high: 3,144/24,206 (13%) had the first revisit and 319/3,144 (10.1%) had the second ED revisit within 72 hours. Diseases of the circulatory (19%) and genitourinary (15.8%) systems were the major reasons for the first ED revisit. The adjusted relative rate (aRR) of 72-hour ED revisits was higher in adults with chronic diseases and aged ≥60 years (aRR=1.360, 95% CI: 1.41–1.83; P=0.001), patients of female gender (aRR=1.24, 95% CI: 1.09–1.41; P=0.001), patients with health insurance coverage (aRR=4.23, 95% CI: 2.60–6.90; P=0.001), patients arriving to ED on a weekend (aRR=2.13, 95% CI: 1.03–4.41; P=0.041), and new patients (aRR=1.47, 95% CI: 1.25–1.73; P=0.001). CONCLUSION: The rate of 72-hour revisits is high among adults with chronic diseases. Advancing age, female gender, health insurance coverage, weekend ED arrival, and new patients are the important predictive factors of the high rate of 72-hour revisits. Continuous quality assessment and monitoring of factors related to patients are needed to reduce the frequency of early ED revisits after discharge.


title: Resource allocation for biomedical research: analysis of investments by major funders

text: BACKGROUND: Data on grants for biomedical research by 10 major funders of health research were collected from the World RePORT platform to explore what is being funded, by whom and where. This analysis is part of the World Health Organization Global Observatory on Health Research and Development’s work with the overall aim to enable evidence-informed deliberations and decisions on new investments in health research and development. The analysis expands on the interactive data visualisations of these data on the Observatory’s website and describes the methods used to enable the categorisation of grants by health categories using automated data-mining techniques. METHODS: Grants data were extracted from the World RePORT platform for 2016, the most recent year with data from all funders. A data-mining algorithm was developed in Java to categorise grants by health category. The analysis explored the distribution of grants by funder, recipient country and organisation, type of grant, health category, average grant duration, and the nature of collaborations between recipients of direct grants and the institutions they collaborated with. RESULTS: Out of a total of 69,420 grants in 2016, the United States of America’s National Institutes of Health funded the greatest number of grants (52,928; 76%) and had the longest average grant duration (6 years and 10 months). Grants for research constituted 70.4% (48,879) of all types of grants, followed by grants for training (13,008; 18.7%) and meetings (2907; 4.2%). Of grant recipients by income group, low-income countries received only 0.2% (165) of all grants. Almost three-quarters of all grants were for non-communicable diseases (72%; 40,035), followed by communicable, maternal, perinatal and nutritional conditions (20%; 11,123), and injuries (6%; 3056). Only 1.1% of grants were for neglected tropical diseases and 0.4% for priority diseases on the WHO list of highly infectious (R&D blueprint) pathogens. CONCLUSIONS: The findings highlight the importance of considering funding decisions by other actors in future health research and capacity-strengthening decisions. This will not only improve efficiency and equity in allocating scarce resources but will also allow informed investment decisions that aim to support research on public health needs and neglected areas.


title: Full genome characterization of two novel Alpha-coronavirus species from Italian bats

text: Abstract Coronaviruses (CoVs) have been detected worldwide in several bat species, which are considered the main reservoir. The attention to the high diversity of CoVs hosted by bats has increased during the last decade due to the high number of human infections caused by two zoonotic Beta-CoVs, SARS-CoV and MERS-CoV, that cause several respiratory diseases. Among coronaviruses, two Alpha-CoV strains (HuCoV-229E and HuCoV-NL63) cause mild respiratory disease that can change to severe disease in children, elderly and individuals affected by illnesses. Phylogenetic analysis conducted on bat Alpha-CoV strains revealed their evolutive correlation to human strains, suggesting their origin in bats. The genome of CoVs is characterized by a high frequency of mutations and recombination events, increasing their ability to switch hosts and their zoonotic potential. In this study, three strains of Alpha-CoV genera detected in Italian bats (Pipistrellus kuhlii) were fully sequenced by Next Generation Sequencing (NGS) and characterized. The complete genome analysis showed the correlation of the Italians strains with a Chinese strain detected in 2013 and, based on CoV molecular species demarcation, two new Alpha-CoV species were established. The analysis of a fragment of the RNA-dependent RNA polymerase (RdRp) showed the correlation of the Italian strains with CoVs that was only detected in the bat Pipistrellus genera (Pipistrellus kuhlii and Pipistrellus Pipistrellus) in European countries.


title: Are loose-fitting powered air-purifying respirators safe during chest compression? A simulation study

text: Abstract Background The application of appropriate personal protective equipment for respiratory protection to health care workers is a cornerstone for providing safe healthcare in emergency departments. We investigated the protective effect and usefulness of loose-fitting powered air-purifying respirators (PAPRs) during chest compression. Methods This was a single-center simulation study performed from May 2019 to July 2019 in a tertiary hospital. We measured the concentrations of ambient aerosol and particles inside the loose-fitting PAPR during chest compression, and this ratio was set as the simulated workplace protecting factor (SWPF). According to the National Institute for Occupational Safety and Health regulations, the assigned protection factor (APF) of loose-fitting PAPRs is 25. Thus, the loose-fitting PAPRs were assumed to have a protective effect when the SWPF were ≥ 250 (APF × 10). We measured the SWPF of PAPR in real time during chest compression and also investigated the problems encountered during its use. Results Ninety-one participants (median age 29 [interquartile range (IQR): 26–32] years; 74% female) completed the simulation. None of the participants failed with SWPF below 250 during three sessions of chest compression. The median (IQR) values of SWPF at three cycles were 17,063 (10,145-26,373), 15,683 (9477-32,394), and 16,960 (7695-27,279). There was no disconnection of equipment or mechanical failures during chest compression. In addition, most participants (83%) replied that they rarely or never experienced difficulty in verbal communication and felt that the loose-fitting PAPR was comfortable. Conclusions The loose-fitting PAPRs provided sufficient respiratory protection without disturbances during chest compression.


title: Prevalence of feline coronavirus antibodies in cats in Bursa province, Turkey, by an enzyme-linked immunosorbent assay

text: Feline sera from Bursa province (Turkey) were assayed for coronavirus antibody using an enzyme-linked immunosorbent assay (ELISA). The study was performed on 100 sera collected from cats belonging to catteries or community shelters and to households. The serum samples were initially tested with the virus neutralisation (VN) test and the results were then compared with the ELISA. The VN yielded 79 negative and 21 positive sera but the ELISA confirmed only 74 as negative. The ELISA-negative sera were also found to be free of feline coronoviruses-specific antibodies by Western blotting. Using the VN as the gold standard test, ELISA had a sensitivity of 100% and a specificity of 93.6%, with an overall agreement of 95%. The Kappa (κ) test indicated high association between the two tests (κ =0.86, 95% confidence interval (CI) 0.743–0.980). The positive predictive value (PPV) was 0.8, and the negative predictive value (NPV) was 0.93. The prevalence of FCoV II antibodies in the sampled population based on the gold standard was 62% (95% CI 0.44–0.77) among multi-cat environments, and 4% (95% CI 0.01–0.11) among single cat households.


title: Pathogenic Mechanisms Of Anti‐Endothelial Cell Antibodies (AECA): Their Prevalence And Clinical Relevance

text: 1. Abstract Anti‐endothelial cell antibodies (AECA) represent a heterogeneous family of autoantibodies directed against structural endothelial proteins, as well as antigens adhering to endothelial cells. Although AECA immunoassays still show a high‐interlaboratory variability, several findings suggest a pathogenic role of these autoantibodies in diseases characterized by endothelial damage. In this chapter, we analyze the knowledge about AECA prevalence, clinical relevance, and their pathogenic role in autoimmune diseases focusing in particular on systemic lupus erythematosus, antiphospholipid syndrome, systemic sclerosis (SSc), and systemic vasculitis.


title: Isolation and experimental inoculation of an S INDEL strain of porcine epidemic diarrhea virus in Japan

text: Abstract In 2013, porcine epidemic diarrhea (PED) was reported in Japan for the first time in 7years and caused significant economic losses. In the present study, we isolated PED virus (PEDV) circulating in Japan using Vero cell cultures and analyzed sequences of S1 genes of these PEDV isolates. Sequence analysis revealed that one of these strains contained distinct insertion and deletions in the S gene (i.e., S INDEL). Furthermore, inoculation of PEDV into 1-week-old pigs demonstrated that the S INDEL strain had a lower pathogenicity than the North American (NA) prototype strain. This is the first report comparing pathogenicity of an S INDEL strain with the NA prototype strain following experimental inoculation. Excretion of PEDV in the feces of S INDEL strain-inoculated pigs occurred later than in NA prototype strain-inoculated pigs. Thus, our findings suggested that the S INDEL strain had different viral dynamics than the NA prototype strain.


title: Ferret Coronavirus-Associated Diseases

text: A novel coronavirus of ferrets was first described in 1993. This coronavirus caused an enteric disease called epizootic catarrhal enteritis (ECE). Recently, a ferret systemic coronavirus (FRSCV)-associated disease was discovered. This new systemic disease resembles the dry form of feline infectious peritonitis (FIP) and has been reported in the United States and Europe. This article addresses the clinical signs, pathology, pathogenesis, diagnosis, treatment, and prevention of this ferret FIP-like disease.


title: The combination of PRRS virus and bacterial endotoxin as a model for multifactorial respiratory disease in pigs

text: Abstract This paper reviews in vivo studies on the interaction between porcine reproductive and respiratory syndrome virus (PRRSV) and LPS performed in the authors’ laboratory. The main aim was to develop a reproducible model to study the pathogenesis of PRRSV-induced multifactorial respiratory disease. The central hypothesis was that respiratory disease results from an overproduction of proinflammatory cytokines in the lungs. In a first series of studies, PRRSV was shown to be a poor inducer of TNF-α and IFN-α in the lungs, whereas IL-1 and the anti-inflammatory cytokine IL-10 were produced consistently during infection. We then set up a dual inoculation model in which pigs were inoculated intratracheally with PRRSV and 3–14 days later with LPS. PRRSV-infected pigs developed acute respiratory signs for 12–24h upon intratracheal LPS inoculation, in contrast to pigs inoculated with PRRSV or LPS only. Moreover, peak TNF-α, IL-1 and IL-6 titers were 10–100 times higher in PRRSV–LPS inoculated pigs than in the singly inoculated pigs and the cytokine overproduction was associated with disease. To further prove the role of proinflammatory cytokines, we studied the effect of pentoxifylline, a known inhibitor of TNF-α and IL-1, on PRRSV–LPS induced cytokine production and disease. The clinical effects of two non-steroidal anti-inflammatory drugs (NSAIDs), meloxicam and flunixin meglumine, were also examined. Pentoxifylline, but not the NSAIDs, significantly reduced fever and respiratory signs from 2 to 6h after LPS. The levels of TNF-α and IL-1 in the lungs of pentoxifylline-treated pigs were moderately reduced, but were still 26 and 3.5-fold higher than in pigs inoculated with PRRSV or LPS only. This indicates that pathways other than inhibition of cytokine production contributed to the clinical improvement. Finally, we studied a mechanism by which PRRSV may sensitize the lungs for LPS. We hypothesized that PRRSV would increase the amount of LPS receptor complex in the lungs leading to LPS sensitisation. Both CD14 and LPS-binding protein, two components of this complex, increased significantly during infection and the amount of CD14 in particular was correlated with LPS sensitisation. The increase of CD14 was mainly due to infiltration of strongly CD14-positive monocytes in the lungs. The PRRSV–LPS combination proved to be a simple and reproducible experimental model for multifactorial respiratory disease in pigs. To what extent the interaction between PRRSV and LPS contributes to the development of complex respiratory disease is still a matter of debate.


title: Featuring advanced translational strategies: Principles, techniques, devices and applications

text: Abstract The ever-emerging developments and innovations on the advanced translational strategies for diagnosing and treating fatal human diseases are substantially re-shaping our future and improving the human health quality. This special issue published several mini-review manuscripts covering fundamental principles, techniques, devices and applications in the related fields. Several investigators including basic research scientists and medical doctors have described recent breakthroughs in the fields of cancer therapy, biomedical engineering, material sciences and their translational medicine from-bench-to-bed into clinical uses.


title: Recent trends in mass spectrometer development

text: Trends in mass analyzer development are reviewed here with an emphasis on tandem mass spectrometers. The move toward “hybridization” of conventional mass analyzers to allow additional instrument functionality in tandem mass spectrometry is discussed.


title: Coronavirus Infection and Diversity in Bats in the Australasian Region

text: Following the SARS outbreak, extensive surveillance was undertaken globally to detect and identify coronavirus diversity in bats. This study sought to identify the diversity and prevalence of coronaviruses in bats in the Australasian region. We identified four different genotypes of coronavirus, three of which (an alphacoronavirus and two betacoronaviruses) are potentially new species, having less than 90% nucleotide sequence identity with the most closely related described viruses. We did not detect any SARS-like betacoronaviruses, despite targeting rhinolophid bats, the putative natural host taxa. Our findings support the virus-host co-evolution hypothesis, with the detection of Miniopterus bat coronavirus HKU8 (previously reported in Miniopterus species in China, Hong Kong and Bulgaria) in Australian Miniopterus species. Similarly, we detected a novel betacoronavirus genotype from Pteropus alecto which is most closely related to Bat coronavirus HKU9 identified in other pteropodid bats in China, Kenya and the Philippines. We also detected possible cross-species transmission of bat coronaviruses, and the apparent enteric tropism of these viruses. Thus, our findings are consistent with a scenario wherein the current diversity and host specificity of coronaviruses reflects co-evolution with the occasional host shift.


title: An ELISA for the detection of rhinovirus specific antibody in serum and nasal secretion

text: Abstract An enzyme-linked immunosorbent assay (ELISA) which detects rhinovirus specific antibody in human sera and nasal secretions, has been developed. This sandwich ELISA utilizes a rabbit antirhinovirus hyperimmune serum as the capture antibody and was found to be very sensitive, detecting rhinovirus specific antibody in the serum at dilutions of 1:106 and 1:103.5 and IgA immunoglobulins, respectively. Thus, this new assay is 102–104 times more sensitive than our standard neutralization test. Furthermore, this increase in sensitivity has enabled us to reliably detect rhinovirus specific immunoglobulins in unconcentrated nasal washings, which are thought to be particularly important for protection against rhinovirus reinfection. A preliminary study of the immune response in human volunteers challenged with rhinovirus using this new ELISA system is presented and further applications and potential of the method are also discussed.


title: Psychosocial burden of healthcare professionals in times of COVID-19 – a survey conducted at the University Hospital Augsburg

text: Objective: The outbreak of COVID-19 was declared a pandemic by the WHO in March 2020. Studies from China, where the virus first spread, have reported increased psychological strain in healthcare professionals. The aim of this study was to investigate the psychosocial burden of physicians and nurses depending on their degree of contact with COVID-19 patients. In addition, we explored which supportive resources they used and which supportive needs they experienced during the crisis. Methods: Data were collected between March and April 2020 at the University Hospital Augsburg. A total of 75 nurses and 35 physicians, working either in a special COVID-19 ward or in a regular ward, took part in the survey. The participants filled in two standardized questionnaires (the Patient Health Questionnaire, PHQ; and the Maslach Burnout Inventory, MBI), and reported their fear of a COVID-19 infection and stress at work on a 10-point Likert scale. Finally, they answered three open-ended questions about causes of burden, supportive resources and needs during the crisis. Results: Nurses working in the COVID-19 wards reported higher levels of stress, exhaustion, and depressive mood, as well as lower levels of work-related fulfilment compared to their colleagues in the regular wards. Physicians reported similar scores independent of their contact with COVID-19 patients. The most common causes for burden were job strain and uncertainty about the future. Psychosocial support as well as leisure time were listed as important resources, and a better infrastructure adjustment to COVID-19 at the hospital (e.g. sufficient staff, keeping teams and working schedules stable) as suggestion for improvement. Conclusions: Our findings indicate that especially nurses working in COVID-19 wards are affected psychologically by the consequences of the pandemic. This might be due to a higher workload and longer time in direct contact with COVID-19 patients, compared to physicians.


To resume noninvasive imaging detection safely after peak period of COVID‐19: experiences from Wuhan China


title: COVID-19 in a patient with active tuberculosis: A rare case-report

text: Scarce data exist about the clinical features of COVID-19 in patients with concomitant active and/or latent tuberculosis (TB). This rare case-report outlines the diagnosis, management and outcome of a sixty year old hypertensive and diabetic patient with serious COVID-19 pneumonia and underlying active TB. The patient was treated successfully in a COVID-19 designated intensive care unit in Saudi Arabia.


title: Construction of an infectious cDNA clone of Enterovirus 71: Insights into the factors ensuring experimental success

text: Abstract Enterovirus 71 (EV 71) is a causative agent of mild Hand Foot and Mouth Disease but is capable of causing severe complications in the CNS in young children. Reverse genetics technology is currently widely used to study the pathogenesis of the virus. The aim of this work was to determine and evaluate the factors which can contribute to infectivity of EV 71 RNA transcripts in vitro. Two strategies, overlapping RT-PCR and long distance RT-PCR, were employed to obtain the full-length genome cDNA clones of the virus. The length of the poly(A) tail and the presence of non-viral 3′-terminal sequences were studied in regard to their effects on infectivity of the in vitro RNA transcripts of EV 71 in cell culture. The data revealed that only cDNA clones obtained after long distance RT-PCR were infectious. No differences were observed in virus titres after transfection with in vitro RNA harbouring a poly(A) tail of 18 or 30 adenines in length, irrespective of the non-viral sequences at the 3′-terminus.