title: Two enzyme immunoassays for the detection of antibody to rodent coronaviruses

text: Abstract Two enzyme immunoassays for detection of antibody to rodent coronaviruses were compared. Mouse hepatitis virus (MHV), strain JHM, antigen was in the form of formalin-fixed, infected 17 C1 1 cells. This antigen detected antibody to the homologous strain of MHV as well as to two heterologous MHV strains and a serologically related rat coronavirus, sialodacryodenititis virus. Antibody titers in assays using horseradish peroxidase (HRP)-conjugated or ureiase-conjugated anti-mouse IgG were substantially higher than in an indirect immunofluorescence assay. The ureiase assay was somewhat more sensitive than the HRP assay. MHV-JHM antigen was stable under a variety of storage conditions for at least two months.


title: Klassevirus 1, a previously undescribed member of the family Picornaviridae, is globally widespread

text: BACKGROUND: Diarrhea is the third leading infectious cause of death worldwide and is estimated to be responsible for approximately 2 million deaths a year. While many infectious causes of diarrhea have been established, approximately 40% of all diarrhea cases are of unknown etiology. In an effort to identify novel viruses that may be causal agents of diarrhea, we used high throughput mass sequencing to analyze stool samples collected from patients with acute diarrhea. RESULTS: Sequences with limited similarity to known picornaviruses were detected in a stool sample collected in Australia from a child with acute diarrhea. Using a combination of mass sequencing, RT-PCR, 5' RACE and 3' RACE, a 6383 bp fragment of the viral genome was sequenced. Phylogenetic analysis demonstrated that this virus was highly divergent from, but most closely related to, members of the genus Kobuvirus. We have tentatively named this novel virus klassevirus 1. We also detected klassevirus 1 by RT-PCR in a diarrhea specimen collected from a patient in St. Louis, United States as well as in untreated sewage collected in Barcelona, Spain. CONCLUSION: Klassevirus 1 is a previously undescribed picornavirus that is globally widespread and present on at least three continents. Further investigations to determine whether klassevirus 1 is a human pathogen are needed.


Preventing COVID-19 and Its Sequela: “There Is No Magic Bullet . . . It's Just Behaviors”


title: Cleavage of spike protein of SARS coronavirus by protease factor Xa is associated with viral infectivity

text: The spike (S) protein of SARS coronavirus (SARS-CoV) has been known to recognize and bind to host receptors, whose conformational changes then facilitates fusion between the viral envelope and host cell membrane, leading to viral entry into target cells. However, other functions of SARS-CoV S protein such as proteolytic cleavage and its implications to viral infection are incompletely understood. In this study, we demonstrated that the infection of SARS-CoV and a pseudovirus bearing the S protein of SARS-CoV was inhibited by a protease inhibitor Ben-HCl. Also, the protease Factor Xa, a target of Ben-HCl abundantly expressed in infected cells, was able to cleave the recombinant and pseudoviral S protein into S1 and S2 subunits, and the cleavage was inhibited by Ben-HCl. Furthermore, this cleavage correlated with the infectivity of the pseudovirus. Taken together, our study suggests a plausible mechanism by which SARS-CoV cleaves its S protein to facilitate viral infection.


title: Organ-specific features of natural killer cells

text: Natural killer (NK) cells can be swiftly mobilized by danger signals and are among the earliest arrivals at target organs of disease. However, the role of NK cells in mounting inflammatory responses is often complex and sometimes paradoxical. Here, we examine the divergent phenotypic and functional features of NK cells, as deduced largely from experimental mouse models of pathophysiological responses in the liver, mucosal tissues, uterus, pancreas, joints and brain. Moreover, we discuss how organ-specific factors, the local microenvironment and unique cellular interactions may influence the organ-specific properties of NK cells.


title: Complete genomic sequence analysis of infectious bronchitis virus Ark DPI strain and its evolution by recombination

text: An infectious bronchitis virus Arkansas DPI (Ark DPI) virulent strain was sequenced, analyzed and compared with many different IBV strains and coronaviruses. The genome of Ark DPI consists of 27,620 nucleotides, excluding poly (A) tail, and comprises ten open reading frames. Comparative sequence analysis of Ark DPI with other IBV strains shows striking similarity to the Conn, Gray, JMK, and Ark 99, which were circulating during that time period. Furthermore, comparison of the Ark genome with other coronaviruses demonstrates a close relationship to turkey coronavirus. Among non-structural genes, the 5'untranslated region (UTR), 3C-like proteinase (3CL(pro)) and the polymerase (RdRp) sequences are 100% identical to the Gray strain. Among structural genes, S1 has 97% identity with Ark 99; S2 has 100% identity with JMK and 96% to Conn; 3b 99%, and 3C to N is 100% identical to Conn strain. Possible recombination sites were found at the intergenic region of spike gene, 3'end of S1 and 3a gene. Independent recombination events may have occurred in the entire genome of Ark DPI, involving four different IBV strains, suggesting that genomic RNA recombination may occur in any part of the genome at number of sites. Hence, we speculate that the Ark DPI strain originated from the Conn strain, but diverged and evolved independently by point mutations and recombination between field strains.


title: Structural elucidation of SARS-CoV-2 vital proteins: Computational methods reveal potential drug candidates against main protease, Nsp12 polymerase and Nsp13 helicase

text: Abstract The recently emerged SARS-CoV-2 caused a major outbreak of coronavirus disease 2019 (COVID-19) and instigated a widespread fear, threatening global health security. To date, no licensed antiviral drugs or vaccines are available against COVID-19 although several clinical trials are underway to test possible therapies. During this urgency situation, computational drug discovery methods provide an alternative to tiresome high-throughput screening, particularly in the hit-to-lead-optimization stage. Identification of small molecules that specifically target viral replication apparatus has indicated highest potential towards antiviral drug discovery. In this work, we present potential compounds that specifically target SARS-CoV-2 vital proteins, including the main protease, Nsp12 RNA polymerase and Nsp13 helicase. An integrative virtual screening and molecular dynamics simulations approach led to the identification of potential binding modes and favourable molecular interaction profile of corresponding compounds. Moreover, the identification of structurally important binding site residues in conserved motifs located inside the active site highlights relative importance of ligand binding based on residual energy decomposition analysis. Although the current study lacks experimental validation, the structural information obtained from this computational study has paved way for the design of targeted inhibitors to combat COVID-19 outbreak.


title: The Usefulness of Platelet-derived Microparticle as Biomarker of Antiplatelet Therapy in Kawasaki Disease

text: Little is known about platelet dynamics and the effect of antiplatelet therapy in Kawasaki disease (KD). This study sought to define platelet activation dynamics in KD patients by assaying platelet-derived microparticles (PDMPs). We measured plasma PDMPs levels in 46 patients with KD using an enzyme-linked immunosorbent assay (ELISA). Blood samples were collected before, at 2–5 days, and 9–15 days after intravenous immunoglobulin (IVIG) infusion, 2 months and 4–5 months after the onset of KD. We measured PDMP levels in 23 febrile and 10 afebrile control patients. In the acute phase of KD patients, PDMP levels increased significantly after IVIG treatment (12.04 ± 5.58 nmol before IVIG infusion vs. 19.81 ± 13.21 nmol at 2–5 days after IVIG infusion, P = 0.006). PDMP levels were negatively correlated with age and positively correlated with procalcitonin levels in the acute phase of KD. No significant difference was found in PDMP levels between KD patients with and without coronary artery lesion (CAL). Elevated PDMP levels after IVIG therapy significantly decreased below the pre-IVIG level in subacute phase (19.81 ± 13.21 nmol at 2–5 days after IVIG infusion vs. 8.33 ± 2.02 nmol at 9–15 days after IVIG infusion, P < 0.001), and PDMP levels stayed below the pre-IVIG level in the convalescent phase, during which antiplatelet therapy was given. However, PDMP levels rebounded after discontinuing aspirin in 17 patients. In conclusion, enhanced platelet activation was noted before treatment of KD and peaked immediately after IVIG treatment. Recurrent rising of PDMP levels was observed after discontinuing aspirin, although there were no significant differences between the PDMP levels at 2 months after the onset of KD and those at 4–5 months after the onset of the disease.


title: Calf-level risk factors for neonatal diarrhea and shedding of Cryptosporidium parvum in Ontario dairy calves

text: Abstract This work was conducted to investigate calf-level factors that influence the risk of neonatal diarrhea and shedding of Cryptosporidium parvum oocysts in calves, on dairy farms in Ontario with histories of calf diarrhea or cryptosporidiosis. Fecal samples were collected weekly for 4 weeks from each of 1045 calves under 30 days of age on 11 dairy farms in south-western Ontario during the summer of 2003 and the winter of 2004. A questionnaire designed to gather information on calf-level management factors was administered on farm for each calf in the study. Samples were examined for C. parvum oocysts by microscopy, and a subset of specimens was also tested for enterotoxigenic Escherichia coli, Salmonella, bovine rotavirus and bovine coronavirus. The consistency of each sample was scored and recorded at the time of collection in order to assess the presence or absence of diarrhea. In addition, a blood sample was taken from each calf upon enrolment in the study, for assessment of maternal antibody transfer and for polymerase chain reaction testing for persistent bovine viral diarrhea virus infection. Using the GLLAMM function in Stata 9.0, multilevel regression techniques were employed to investigate associations between management practices and the risk of C. parvum shedding or diarrhea. C. parvum oocysts were detected in the feces of 78% of the 919 calves from which all four fecal samples had been collected. Furthermore, 73% of the 846 calves for which all four fecal consistency scores had been recorded were diarrheic at the time of collection of at least one sample. Significant predictors of the calf-level risk of C. parvum shedding included the use of calf diarrhea prophylaxis in pregnant cows, and the type of maternity facilities in which the calves were born. Factors associated with an increased risk of diarrhea were leaving the calf with the dam for more than an hour after birth, and the birth of a calf in the summer as opposed to winter. Calves shedding C. parvum oocysts had 5.3 (95% CI 4.4, 6.4) times the odds of diarrhea than non-shedding calves, controlling for other factors included in the final multivariable model. Furthermore, infected calves shedding more than 2.2×105 oocysts per gram of feces were more likely to scour than infected calves shedding lower numbers of oocysts (OR=6.1, 95% CI 4.8, 7.8). The odds of diarrhea in calves shedding oocysts that had been allowed to remain with their dams for more than an hour were higher than the odds of diarrhea in shedding calves that had been separated from their dams within an hour after birth.


title: Withanone and caffeic acid phenethyl ester are predicted to interact with main protease (M(pro)) of SARS-CoV-2 and inhibit its activity

text: The recent novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2/2019-nCoV) has caused a large number of deaths around the globe. There is an urgent need to understand this new virus and develop prophylactic and therapeutic drugs. Since drug development is an expensive, intense and time-consuming path, timely repurposing of the existing drugs is often explored wherein the research avenues including genomics, bioinformatics, molecular modeling approaches offer valuable strengths. Here, we have examined the binding potential of Withaferin-A (Wi-A), Withanone (Wi-N) (active withanolides of Ashwagandha) and Caffeic Acid Phenethyl Ester (CAPE, bioactive ingredient of propolis) to a highly conserved protein, M(pro) of SARS-CoV-2. We found that Wi-N and CAPE, but not Wi-A, bind to the substrate-binding pocket of SARS-CoV-2 M(pro) with efficacy and binding energies equivalent to an already claimed N3 protease inhibitor. Similar to N3 inhibitor, Wi-N and CAPE were interacting with the highly conserved residues of the proteases of coronaviruses. The binding stability of these molecules was further analyzed using molecular dynamics simulations. The binding free energies calculated using MM/GBSA for N3 inhibitor, CAPE and Wi-N were also comparable. Data presented here predicted that these natural compounds may possess the potential to inhibit the functional activity of SARS-CoV-2 protease (an essential protein for virus survival), and hence (i) may connect to save time and cost required for designing/development, and initial screening for anti-COVID drugs, (ii) may offer some therapeutic value for the management of novel fatal coronavirus disease, (iii) warrants prioritized further validation in the laboratory and clinical tests. Communicated by Ramaswamy H. Sarma


title: Novel Coronavirus and Astrovirus in Delaware Bay Shorebirds

text: BACKGROUND: Wild birds are an important but to some extent under-studied reservoir for emerging pathogens. We used unbiased sequencing methods for virus discovery in shorebird samples from the Delaware Bay, USA; an important feeding ground for thousands of migratory birds. FINDINGS: Analysis of shorebird fecal samples indicated the presence of a novel astrovirus and coronavirus. A sanderling sample yielded sequences with distant homology to avian nephritis virus 1, an astrovirus associated with acute nephritis in poultry. A ruddy turnstone sample yielded sequences with homology to deltacoronaviruses. CONCLUSIONS: Our findings highlight shorebirds as a virus reservoir and the need to closely monitor wild bird populations for the emergence of novel virus variants.


title: Organisation d’un service de radiothérapie pendant l’épidémie de COVID-19 : expérience du centre hospitalier de Mulhouse

text: Résumé L’épidémie de COVID-19 continue de croître de manière exponentielle dans notre pays. Si la majorité des formes sont bénignes, les patients atteints de cancer sont à risque de voir se développer une forme grave de la maladie. Les services de radiothérapie sont un lieu à potentiel de contamination en raison du nombre de patients traités et de personnels présent. Leur organisation pendant la période épidémique vise à assurer la continuité des soins tout en limitant le risque de décès dû à une contamination par le SARS-CoV-2 (virus responsable de la COVID-19). Dans le service de radiothérapie du groupe hospitalier de la région de Mulhouse et Sud-Alsace, cette organisation s’articule en cinq points : la protection des personnels médicaux et paramédicaux, la protection des patients en cours de traitement, la détection des patients suspects d’être atteints de COVID-19 et leur prise en charge, la réorganisation du circuit patient et les mesures concernant l’organisation du système qualité du service. Nos pistes de réflexion, débutée dès le début de l’épidémie dans notre département, nous permettent de préserver au maximum l’accès aux soins radiothérapiques en anticipant le risque de diffusion du virus. Grâce à des réunions bihebdomadaires, nous continuons à nous adapter à l’évolution épidémique dans notre service, en tenant compte de nos moyens matériels. La possibilité de réaliser des tests de diagnostic chez tous les patients suspects nous permettrait également d’affiner nos procédures. Summary The COVID-19 outbreak grows exponentially in our country. Despite most of patients develops benign symptoms, cancer patients are at risk of a severe form of the disease. Radiotherapy centres are a potential contamination place due to the number of patients treated and staff present. Their organization during the outbreak period aims to ensure continuity of care while limiting the risk of death from COVID-19. In the radiotherapy department of Mulhouse hospital (France), we pointed five points out: protection of medical and paramedical staff, protection of patients undergoing treatment, detection of patients suspected of being infected by SARS-CoV-2 and their management, reorganization of the patient circuit and measures regarding the quality management. This reflection, which began at the beginning of the outbreak in our city, allows us to preserve the access to radiotherapy treatments by anticipating the risk of spreading the virus. Through biweekly meetings, we continue to adapt to the epidemic in our department, considering our material resources. The ability to perform diagnostic tests in all suspect patients would also allow us to refine our procedures.


title: Toxicology Advances for 21st Century Chemical Pollution

text: Pollution represents a leading threat to global health and ecosystems. Systems-based initiatives, including Planetary Health, EcoHealth, and One Health, require theoretical and translational platforms to address chemical pollution. Comparative and predictive toxicology are providing integrative approaches for identifying problematic contaminants, designing less hazardous alternatives, and reducing the impacts of chemical pollution.


title: A Case of Feline T-cell Lymphoma with Tropism for Striated Muscle and Peripheral Nerve

text: Summary An 11-year-old female American shorthair cat was presented with a 3-month history of hindlimb ataxia and knuckling of the left forelimb. Clinical abnormalities included weight loss, hyperaesthesia of the neck and back, cardiac murmur and systemic muscle atrophy. The cat died 10 days after the initial presentation and a necropsy examination was performed. Grossly, extensive pale lesions were seen in the wall of the left ventricle and the septum of the heart. There were no detectable masses in the heart, skeletal muscles or peripheral nerves. Histopathological examination revealed diffuse, extensive infiltration of atypical lymphoid cells in the heart; the cardiac muscles were markedly degenerate and atrophic and were replaced by the neoplastic cells. Neoplastic cells with similar morphology were seen in all specimens of the skeletal muscles and peripheral nerves. Clonality analysis of the paraffin wax-embedded heart tissue revealed a monoclonal rearrangement of the gene encoding the T-cell receptor γ chain. Based on these findings, the case was diagnosed as T-cell lymphoma with tropism for striated muscle and peripheral nerve.


COVID-19 and Elective Surgery: 7 Practical Tips for a Safe, Successful, and Sustainable Reboot


title: A serological assay to detect SARS-CoV-2 antibodies in at-home collected finger-prick dried blood spots

text: Accurate surveillance of coronavirus disease 2019 (COVID-19) incidence requires large-scale testing of the population. Current testing methods require in-person collection of biospecimens by a healthcare worker, limiting access of individuals who do not have access to testing facilities while placing both the patient and healthcare worker at risk of exposure to infection. We report the development and validation of a at-home finger-prick dried blood spot collection kit and an analysis method. We demonstrated 100% sensitivity and specificity using at-home collected specimens across the US. Such methods may facilitate the conduct of unbiased serosurveys within hard to reach populations and help reduce the sample collection burden of serological testing on both health care systems and individuals alike.


title: An Infectious cDNA Clone of SARS-CoV-2

text: Summary The ongoing pandemic of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), underscores the urgency to develop experimental systems for studying this virus and identifying countermeasures. We report a reverse genetic system for SARS-CoV-2. Seven complimentary DNA (cDNA) fragments spanning the SARS-CoV-2 genome were assembled into a full-genome cDNA. RNA transcribed from the full-genome cDNA was highly infectious after electroporation into cells, producing 2.9 × 106 plaque-forming unit (PFU)/mL of virus. Compared with a clinical isolate, the infectious-clone-derived SARS-CoV-2 (icSARS-CoV-2) exhibited similar plaque morphology, viral RNA profile, and replication kinetics. Additionally, icSARS-CoV-2 retained engineered molecular markers and did not acquire other mutations. We generated a stable mNeonGreen SARS-CoV-2 (icSARS-CoV-2-mNG) by introducing this reporter gene into ORF7 of the viral genome. icSARS-CoV-2-mNG was successfully used to evaluate the antiviral activities of interferon (IFN). Collectively, the reverse genetic system and reporter virus provide key reagents to study SARS-CoV-2 and develop countermeasures.


title: Efficacy and safety of aerosol inhalation of recombinant human interferon α1b (IFNα1b) injection for noninfluenza viral pneumonia, a multicenter, randomized, double-blind, placebo-controlled trial

text: BACKGROUND: To investigate the efficacy and safety of aerosol inhalation of recombinant human interferon α1b (IFNα1b) injection for noninfluenza viral pneumonia. METHODS: One hundred sixty-four patients with noninfluenza viral pneumonia were divided into IFNα1b and control groups. The IFNα1b group received routine treatment + aerosol inhalation of recombinant human IFNα1b injection (50 μg × 2 injections, bid). The control group received routine treatment + IFN analog (two injections, bid). Overall response rate (ORR) of five kinds clinical symptoms. Further outcomes were daily average score and the response rate of each of the symptoms above. RESULTS: A total of 163 patients were included in the full analysis set (FAS) and 151 patients were included in the per-protocol set (PPS). After 7 days of treatment, ORR of clinical symptoms was higher in IFNα1b group than that in control group for both the FAS and PPS. Moreover, after 7 days of treatment, the daily score of three efficacy indexes including expectoration, respiratory rate, and pulmonary rales were improved. The ORRs for expectoration and pulmonary rales were higher in the IFNα1b group than in the control group (P < 0.05). There were no significant differences of the ORRs for coughing, chest pain and respiratory rate between the two groups (P > 0.05). The incidence of adverse events was 6.5% (n = 5) in IFNα1b group and 3.5% (n = 3) in control group (P > 0.05). CONCLUSION: Aerosol inhalation of recombinant human IFNα1b is safe and it can improve the clinical symptoms of noninfluenza viral pneumonia.


The relevance of complement to virus biology


Chloroquine reduces Th17 cell differentiation by stimulating T-bet expression in T cells


title: Respiratory Viruses and Atypical Bacteria Co-Infection in Children with Acute Respiratory Infection

text: BACKGROUND: Acute respiratory infections (ARI) are one of the prevalent pediatric diseases. Coinfections of respiratory viruses and atypical bacterial respiratory pathogens are common. AIM: This study aimed to determine the prevalence of co-infection between respiratory pathogens including viruses, bacteria and atypical bacteria in a sample of Egyptian children presenting with symptoms of acute respiratory tract infection. METHODS: This one-year prospective cohort study conducted in Abo El Rish Pediatric Hospital, Cairo University over one year included children presenting with symptoms of acute respiratory infection. Enrolled children were subjected to nasopharyngeal swabs or throat swabs and then processed to detect viral, bacterial and atypical bacterial causative agents by culture), retrotranscription polymerase, Monoplex polymerase chain reaction (PCR) and Multiplex PCR. RESULTS: Viral etiological agents were detected in 20 cases (20.8%), while 76 patients (79.2%) had no definite viral aetiology. The most abundant virus detected was Rhinovirus in 36 (27.3%), followed by 21 (15.9%) were positive for RSV, 12 (9.1%) were positive for HMPV, 6 (4.5%) were positive for adenovirus and 3 (2.3%) were positive for influenza B. For Atypical bacterial causes Mycoplasma were positive for 9 (6.8%) cases and one case was positive for Bordetella parapertussis. Viral and atypical bacteria Co infection were detected in 14 (10.6%) of cases. CONCLUSION: These results suggest that coinfection with bacteria or atypical bacteria in children with acute respiratory tract infection is common and this co-infection can induce serious illness. The multiplex reverse-transcriptase polymerase chain reaction should become an essential tool for epidemiological studies and can fill the gap between clinical presentation and definitive diagnosis.


title: Emerging Structural Insights into Glycoprotein Quality Control Coupled with N-Glycan Processing in the Endoplasmic Reticulum

text: In the endoplasmic reticulum (ER), the sugar chain is initially introduced onto newly synthesized proteins as a triantennary tetradecasaccharide (Glc(3)Man(9)GlcNAc(2)). The attached oligosaccharide chain is subjected to stepwise trimming by the actions of specific glucosidases and mannosidases. In these processes, the transiently expressed N-glycans, as processing intermediates, function as signals for the determination of glycoprotein fates, i.e., folding, transport, or degradation through interactions of a series of intracellular lectins. The monoglucosylated glycoforms are hallmarks of incompletely folded states of glycoproteins in this system, whereas the outer mannose trimming leads to ER-associated glycoprotein degradation. This review outlines the recently emerging evidence regarding the molecular and structural basis of this glycoprotein quality control system, which is regulated through dynamic interplay among intracellular lectins, glycosidases, and glycosyltransferase. Structural snapshots of carbohydrate-lectin interactions have been provided at the atomic level using X-ray crystallographic analyses. Conformational ensembles of uncomplexed triantennary high-mannose-type oligosaccharides have been characterized in a quantitative manner using molecular dynamics simulation in conjunction with nuclear magnetic resonance spectroscopy. These complementary views provide new insights into glycoprotein recognition in quality control coupled with N-glycan processing.


title: Targeting cancer stem cells with dietary phytochemical - Repositioned drug combinations

text: Abstract The tumor microenvironment is complex with the cancer stem cell (CSC) as a member within its community. This population possesses the capacity to self-renew and to cause cellular heterogeneity of the tumor. CSCs are resistant to conventional anti-proliferative drugs. In order to be curative, it is imperative that CSCs must be eliminated by cancer therapy. A variety of dietary phytochemicals and repositioned drugs can act synergistically with conventional anti-cancer agents. In this review, we advocate the development of a novel approach, namely combination therapy by incorporating both phytochemicals and repositioned drugs to target CSCs. We cover select dietary phytochemicals (curcumin, resveratrol, EGCG, genistein) and repurposed drugs (metformin, niclosamide, thioridazine, chloroquine). Five of the eight (curcumin, resveratrol, EGCG, genistein, metformin) are listed in “The Halifax Project”, that explores “the concept of a low-toxicity ‘broad-spectrum’ therapeutic approach that could simultaneously target many key pathways and mechanisms” [1]. For these compounds, we discuss their mechanisms of action, in which models their anti-CSC activities were identified, as well as advantages, challenges and potentials of combination therapy.


title: Quantifying risks and interventions that have affected the burden of lower respiratory infections among children younger than 5 years: an analysis for the Global Burden of Disease Study 2017

text: BACKGROUND: Despite large reductions in under-5 lower respiratory infection (LRI) mortality in many locations, the pace of progress for LRIs has generally lagged behind that of other childhood infectious diseases. To better inform programmes and policies focused on preventing and treating LRIs, we assessed the contributions and patterns of risk factor attribution, intervention coverage, and sociodemographic development in 195 countries and territories by drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) LRI estimates. METHODS: We used four strategies to model LRI burden: the mortality due to LRIs was modelled using vital registration data, demographic surveillance data, and verbal autopsy data in a predictive ensemble modelling tool; the incidence of LRIs was modelled using population representative surveys, health-care utilisation data, and scientific literature in a compartmental meta-regression tool; the attribution of risk factors for LRI mortality was modelled in a counterfactual framework; and trends in LRI mortality were analysed applying changes in exposure to risk factors over time. In GBD, infectious disease mortality, including that due to LRI, is among HIV-negative individuals. We categorised locations based on their burden in 1990 to make comparisons in the changing burden between 1990 and 2017 and evaluate the relative percent change in mortality rate, incidence, and risk factor exposure to explain differences in the health loss associated with LRIs among children younger than 5 years. FINDINGS: In 2017, LRIs caused 808 920 deaths (95% uncertainty interval 747 286–873 591) in children younger than 5 years. Since 1990, there has been a substantial decrease in the number of deaths (from 2 337 538 to 808 920 deaths; 65·4% decrease, 61·5–68·5) and in mortality rate (from 362·7 deaths [330·1–392·0] per 100 000 children to 118·9 deaths [109·8–128·3] per 100 000 children; 67·2% decrease, 63·5–70·1). LRI incidence declined globally (32·4% decrease, 27·2–37·5). The percent change in under-5 mortality rate and incidence has varied across locations. Among the risk factors assessed in this study, those responsible for the greatest decrease in under-5 LRI mortality between 1990 and 2017 were increased coverage of vaccination against Haemophilus influenza type b (11·4% decrease, 0·0–24·5), increased pneumococcal vaccine coverage (6·3% decrease, 6·1–6·3), and reductions in household air pollution (8·4%, 6·8–9·2). INTERPRETATION: Our findings show that there have been substantial but uneven declines in LRI mortality among countries between 1990 and 2017. Although improvements in indicators of sociodemographic development could explain some of these trends, changes in exposure to modifiable risk factors are related to the rates of decline in LRI mortality. No single intervention would universally accelerate reductions in health loss associated with LRIs in all settings, but emphasising the most dominant risk factors, particularly in countries with high case fatality, can contribute to the reduction of preventable deaths. FUNDING: Bill & Melinda Gates Foundation.


title: Pyruvate Affects Inflammatory Responses of Macrophages During Influenza A Virus Infection

text: Pyruvate is the end product of glycolysis and transported into the mitochondria for use in the tricarboxylic acid (TCA) cycle. It is also a common additive in cell culture media. We discovered that inclusion of sodium pyruvate in culture media during infection of mouse bone marrow derived macrophages with influenza A virus impaired cytokine production (IL-6, IL-1β, and TNF-α). Sodium pyruvate did not inhibit viral RNA replication. Instead, the addition of sodium pyruvate alters cellular metabolism and diminished mitochondrial reactive oxygen species (ROS) production and lowered immune signaling. Overall, sodium pyruvate affects the immune response produced by macrophages but does not inhibit virus replication.


title: Additional hypotheses about why COVID‐19 is milder in children than adults

text: We read with great interest the editorial by Brodin discussing why COVID-19 appears to be so mild in children (1). In particular, the author discussed the potential theories that could explain why children have a lower incidence and milder clinical manifestations than adults. However, we feel it is important to present some other additional hypotheses in order to address all the potential theories.


title: Burden of Disease, Injuries, and Risk Factors in the Kingdom of Saudi Arabia, 1990–2010

text: INTRODUCTION: We report the burden of disease and risk factors measured by causes of death, years of life lost attributable to premature mortality (YLLs), years of life lived with disability (YLDs), and disability-adjusted life years (DALYs) for 1990, 2005, and 2010 in the Kingdom of Saudi Arabia (KSA). METHODS: We used the Global Burden of Diseases 2010 (GBD 2010) methodology to estimate the country-level burden of disease in KSA. We used data from systematic reviews of the literature, household survey data, antenatal clinic surveillance data, reportable disease notifications, disease registries, hospital admissions data, outpatient visit data, population-based cancer registries, active screening data, and other administrative data. RESULTS: Noncommunicable diseases and road traffic injuries became the leading cause of death and disability in KSA in 2010. Elevated body mass index was the leading risk factor for disease (7.02% for males and 4.61% for females in 2010). High glucose levels were the second leading disease risk factor for females (3.28%) and third for males (6.25%) in 2010. Preterm birth complications were the main cause for DALYs in 1990; however, in 2010, the leading cause of DALYs for males was road traffic injuries (12.40%) and for females it was major depressive disorder (7.88%). CONCLUSION: KSA is facing a rising burden of noncommunicable diseases and road traffic injuries as a result of rapid changes in behaviors. Our results demonstrate the need for major intervention to reduce these burdens and to engage other sectors of the government and the community in these efforts.


Temblor y ataxia en COVID-19


title: Neurological involvement of coronavirus disease 2019: a systematic review

text: BACKGROUND: In December 2019, unexplained cases of pneumonia emerged in Wuhan, China, which were found to be secondary to the novel coronavirus SARS-CoV-2. On March 11, 2020, the WHO declared the Coronavirus Disease 2019 (COVID-2019) outbreak, a pandemic. OBJECTIVE: To clarify the neurological complications of SARS-CoV-2 infection including the potential mechanisms and therapeutic options. METHODS: We conducted a systematic literature search from December 01, 2019 to May 14, 2020 using multiple combinations of keywords from PubMed and Ovid Medline databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included articles with cases of COVID-19 where neurological involvement was evident. RESULTS: We were able to identify 82 cases of COVID-19 with neurological complications. The mean age was 62.3 years. 37.8% of the patients were women (n = 31). 48.8% of the patients (n = 40) had cerebrovascular insults, 28% (n = 23) had neuromuscular disorders, and 23% of the patients (n = 19) had encephalitis or encephalopathy. CONCLUSIONS: Neurological manifestations of COVID-19 are not rare, especially large vessel stroke, Guillain–Barre syndrome, and meningoencephalitis. Moving forward, further studies are needed to clarify the prevalence of the neurological complications of SARS-CoV-2 infection, investigate their biological backgrounds, and test treatment options. Physicians should be cautious not to overlook other neurological diagnoses that can mimic COVID-19 during the pandemic. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00415-020-09990-2) contains supplementary material, which is available to authorized users.


title: Our First Month of Delivering the Prostate Cancer Diagnostic Pathway within the Limitations of COVID‐19 Using Local Anaesthetic Transperineal Biopsy

text: The COVID‐19 pandemic is impacting all urological cancer services. On March 19(th) the British Association of Urological Surgeons (BAUS) provided pragmatic guidance for prostate cancer diagnostic services (Table 1).(1)


title: RNA-Binding Domain in the Nucleocapsid Protein of Gill-Associated Nidovirus of Penaeid Shrimp

text: Gill-associated virus (GAV) infects Penaeus monodon shrimp and is the type species okavirus in the Roniviridae, the only invertebrate nidoviruses known currently. Electrophoretic mobility shift assays (EMSAs) using His(6)-tagged full-length and truncated proteins were employed to examine the nucleic acid binding properties of the GAV nucleocapsid (N) protein in vitro. The EMSAs showed full-length N protein to bind to all synthetic single-stranded (ss)RNAs tested independent of their sequence. The ssRNAs included (+) and (−) sense regions of the GAV genome as well as a (+) sense region of the M RNA segment of Mourilyan virus, a crustacean bunya-like virus. GAV N protein also bound to double-stranded (ds)RNAs prepared to GAV ORF1b gene regions and to bacteriophage M13 genomic ssDNA. EMSAs using the five N protein constructs with variable-length N-terminal and/or C-terminal truncations localized the RNA binding domain to a 50 amino acid (aa) N-terminal sequence spanning Met(11) to Arg(60). Similarly to other RNA binding proteins, the first 16 aa portion of this sequence was proline/arginine rich. To examine this domain in more detail, the 18 aa peptide (M(11)PVRRPLPPQPPRNARLI(29)) encompassing this sequence was synthesized and found to bind nucleic acids similarly to the full-length N protein in EMSAs. The data indicate a fundamental role for the GAV N protein proline/arginine-rich domain in nucleating genomic ssRNA to form nucleocapsids. Moreover, as the synthetic peptide formed higher-order complexes in the presence of RNA, the domain might also play some role in protein/protein interactions stabilizing the helical structure of GAV nucleocapsids.


title: Central Nervous System Stromal Cells Control Local CD8(+) T Cell Responses during Virus-Induced Neuroinflammation

text: Stromal cells generate a complex cellular scaffold that provides specialized microenvironments for lymphocyte activation in secondary lymphoid organs. Here, we assessed whether local activation of stromal cells in the central nervous system (CNS) is mandatory to transfer immune recognition from secondary lymphoid organs into the infected tissue. We report that neurotropic virus infection in mice triggered the establishment of such stromal cell niches in the CNS. CNS stromal cell activation was dominated by a rapid and vigorous production of CC-motif chemokine receptor (CCR) 7 ligands CCL19 and CCL21 by vascular endothelial cells and adjacent fibroblastic reticular cell (FRC)-like cells in the perivascular space. Moreover, CCR7 ligands produced by CNS stromal cells were crucial to support recruitment and local re-activation of antiviral CD8(+) T cells and to protect the host from lethal neuroinflammatory disease, indicating that CNS stromal cells generate confined microenvironments that control protective T cell immunity.


Perinatal Mental Health during the COVID-19 Pandemic


title: Synthesis of (R)- and (S)-β-hydroxyphosphonate acyclonucleosides: structural analogues of Adefovir (PMEA)

text: Abstract A synthetic pathway to new acyclonucleoside phosphonates, as analogues of Adefovir, is described. The reduction of an acyclonucleoside β-ketophosphonate, readily available from the nucleobase and benzylacrylate, afforded a mixture of (R)- and (S)-β-hydroxyphosphonate derivatives which was resolved. The assignment of the absolute configuration was proposed on the basis of NMR studies and was supported by molecular modelling studies.


title: The Structure of DC-SIGNR with a Portion of its Repeat Domain Lends Insights to Modeling of the Receptor Tetramer

text: The dendritic cell-specific ICAM-3 non-integrin (DC-SIGN) and its close relative DC-SIGNR recognize various glycoproteins, both pathogenic and cellular, through the receptor lectin domain-mediated carbohydrate recognition. While the carbohydrate-recognition domains (CRD) exist as monomers and bind individual carbohydrates with low affinity and are permissive in nature, the full-length receptors form tetramers through their repeat domain and recognize specific ligands with high affinity. To understand the tetramer-based ligand binding avidity, we determined the crystal structure of DC-SIGNR with its last repeat region. Compared to the carbohydrate-bound CRD structure, the structure revealed conformational changes in the calcium and carbohydrate coordination loops of CRD, an additional disulfide bond between the N and the C termini of the CRD, and a helical conformation for the last repeat. On the basis of the current crystal structure and other published structures with sequence homology to the repeat domain, we generated a tetramer model for DC-SIGN/R using homology modeling and propose a ligand-recognition index to identify potential receptor ligands.


title: Putative vaccine breakthrough event associated with heterotypic rotavirus infection in newborn calves, Turkey, 2015

text: Abstract Group A rotaviruses (RVA) are regarded as major enteric pathogens of large ruminants, including cattle. Rotavirus vaccines administered to pregnant cows are commonly used to provide passive immunity that protects newborn calves from the clinical disease. In this study we report the detection of RVA from calves with severe diarrhea in a herd regularly vaccinated to prevent enteric infections including RVA. Diarrheic disease was observed in newborn calves aged 4–15days, with high morbidity and mortality rates, but no diarrhea was seen in adult animals. Rotavirus antigen was detected by enzyme-immunoassay in the intestinal content or the fecal samples of all examined animals. Besides RVA, bovine coronavirus and bovine enteric calicivirus were detected in some samples. Selected RVA strains were characterized by whole genome sequencing. Two strains, RVA/Cow-wt/TUR/Amasya-1/2015/G8P[5] and RVA/Cow-wt/TUR/Amasya-2/2015/G8P[5] were genotyped as G8-P[5]-I2-R2-C2-M2-A3-N2-T6-E2-H3 and showed >99% nucleotide sequence identity among themselves. This genomic constellation is fairly common among bovine RVA strains; however, phylogenetic analysis of the G8 VP7 gene showed close genetic relationship to some European human RVA strains (up to 98.4% nt identity). Our findings is the first indication regarding the circulation of G8 RVA strains in Turkey. Given that the administered RVA vaccines contained type G6 and G10 VP7 antigens some concerns raised with regard to the level of heterotypic protection elicited by the vaccine strains against circulating bovine G8 RVA strains. Enhancement of surveillance of circulating RVA strains in calves across Turkey is needed to support ongoing vaccination programs.


How will the COVID-19 pandemic affect the catalysis community?


title: Why should cell biologists study microbial pathogens?

text: One quarter of all deaths worldwide each year result from infectious diseases caused by microbial pathogens. Pathogens infect and cause disease by producing virulence factors that target host cell molecules. Studying how virulence factors target host cells has revealed fundamental principles of cell biology. These include important advances in our understanding of the cytoskeleton, organelles and membrane-trafficking intermediates, signal transduction pathways, cell cycle regulators, the organelle/protein recycling machinery, and cell-death pathways. Such studies have also revealed cellular pathways crucial for the immune response. Discoveries from basic research on the cell biology of pathogenesis are actively being translated into the development of host-targeted therapies to treat infectious diseases. Thus there are many reasons for cell biologists to incorporate the study of microbial pathogens into their research programs.


title: Mortality Risk Factors for Middle East Respiratory Syndrome Outbreak, South Korea, 2015

text: As of July 15, 2015, the South Korean Ministry of Health and Welfare had reported 186 case-patients with Middle East respiratory syndrome in South Korea. For 159 case-patients with known outcomes and complete case histories, we found that older age and preexisting concurrent health conditions were risk factors for death.


title: Genomic characterization of the unclassified bovine enteric virus Newbury agent-1 (Newbury1) endorses a new genus in the family Caliciviridae

text: Abstract The pathogenic bovine enteric virus, Newbury agent-1 (Bo//Newbury1/1976/UK), first identified in 1976, was characterized as a possible calicivirus by morphology, buoyant density in CsCl and the presence of a single capsid protein but genomic sequence could not be obtained. In the present study, the complete genome sequence of Newbury1 was determined and classified Newbury1 in a new genus of the Caliciviridae. The Newbury1 genome, of 7454 nucleotides, had two predicted open reading frames (ORFs). ORF1 encoded the non-structural and contiguous capsid proteins. ORF2 encoded a basic protein characteristic of the family Caliciviridae. Compared to the 4 recognized Caliciviridae genera, Norovirus, Sapovirus, Lagovirus and Vesivirus, Newbury1 had less than 39% amino acid (47% nucleotide) identity in the complete 2C-helicase, 3C-protease, 3D-polymerase and capsid regions but had 89% to 98% amino acid (78% to 92% nucleotide) identity to the recently characterized NB virus in these regions. By phylogenetic analyses, Newbury1 and NB viruses formed a distinct clade independent of the 4 recognized genera. However, amino acid identities showed that Newbury1 and the NB virus were distinct polymerase types (90% amino acid identity), but their complete capsid proteins were almost identical (98% amino acid identity). Analyses of contemporary viruses showed that the two polymerase genotypes, Newbury1 and NB, were circulating in UK cattle and antibody to Newbury1-like viruses was common in cattle sera. The present study defined the existence of a new genus in the Caliciviridae that we propose be named Becovirus or Nabovirus to distinguish the new clade from bovine noroviruses.


title: Viruses associated with influenza‐like‐illnesses in Papua New Guinea, 2010

text: Influenza‐like‐illness can be caused by a wide range of respiratory viruses. The etiology of influenza‐like‐illness in developing countries such as Papua New Guinea is poorly understood. The etiological agents associated with influenza‐like‐illness were investigated retrospectively for 300 nasopharyngeal swabs received by the Papua New Guinea National Influenza Centre in 2010. Real‐time PCR/RT‐PCR methods were used for the detection of 13 respiratory viruses. Patients with influenza‐like‐illness were identified according to the World Health Organization case definition: sudden onset of fever (>38°C), with cough and/or sore throat, in the absence of other diagnoses. At least one viral respiratory pathogen was detected in 66.3% of the samples tested. Rhinoviruses (17.0%), influenza A (16.7%), and influenza B (12.7%) were the pathogens detected most frequently. Children <5 years of age presented with a significantly higher rate of at least one viral pathogen and a significantly higher rate of co‐infections with multiple viruses, when compared to all other patients >5 years of age. Influenza B, adenovirus, and respiratory syncytial virus were all detected at significantly higher rates in children <5 years of age. This study confirmed that multiple respiratory viruses are circulating and contributing to the presentation of influenza‐like‐illness in Papua New Guinea. J. Med. Virol. 86:899–904, 2014. © 2013 Wiley Periodicals, Inc.


title: Transcriptomic Signatures of Tacaribe Virus-Infected Jamaican Fruit Bats

text: Tacaribe virus (TCRV) is a mammalian arenavirus that was first isolated from artibeus bats in the 1950s. Subsequent experimental infection of Jamaican fruit bats (Artibeus jamaicensis) caused a disease similar to that of naturally infected bats. Although substantial attention has focused on bats as reservoir hosts of viruses that cause human disease, little is known about the interactions between bats and their pathogens. We performed a transcriptome-wide study to illuminate the response of Jamaican fruit bats experimentally infected with TCRV. Differential gene expression analysis of multiple tissues revealed global and organ-specific responses associated with innate antiviral responses, including interferon alpha/beta and Toll-like receptor signaling, activation of complement cascades, and cytokine signaling, among others. Genes encoding proteins involved in adaptive immune responses, such as gamma interferon signaling and costimulation of T cells by the CD28 family, were also altered in response to TCRV infection. Immunoglobulin gene expression was also elevated in the spleens of infected bats, including IgG, IgA, and IgE isotypes. These results indicate an active innate and adaptive immune response to TCRV infection occurred but did not prevent fatal disease. This de novo assembly provides a high-throughput data set of the Jamaican fruit bat and its host response to TCRV infection, which remains a valuable tool to understand the molecular signatures involved in antiviral responses in bats. IMPORTANCE As reservoir hosts of viruses associated with human disease, little is known about the interactions between bats and viruses. Using Jamaican fruit bats infected with Tacaribe virus (TCRV) as a model, we characterized the gene expression responses to infection in different tissues and identified pathways involved with the response to infection. This report is the most detailed gene discovery work in the species to date and the first to describe immune gene expression responses in bats during a pathogenic viral infection.


Caregiving at a Physical Distance: Initial Thoughts for COVID‐19 and Beyond


title: Plant‐produced candidate countermeasures against emerging and reemerging infections and bioterror agents

text: Despite progress in the prevention and treatment of infectious diseases, they continue to present a major threat to public health. The frequency of emerging and reemerging infections and the risk of bioterrorism warrant significant efforts towards the development of prophylactic and therapeutic countermeasures. Vaccines are the mainstay of infectious disease prophylaxis. Traditional vaccines, however, are failing to satisfy the global demand because of limited scalability of production systems, long production timelines and product safety concerns. Subunit vaccines are a highly promising alternative to traditional vaccines. Subunit vaccines, as well as monoclonal antibodies and other therapeutic proteins, can be produced in heterologous expression systems based on bacteria, yeast, insect cells or mammalian cells, in shorter times and at higher quantities, and are efficacious and safe. However, current recombinant systems have certain limitations associated with production capacity and cost. Plants are emerging as a promising platform for recombinant protein production due to time and cost efficiency, scalability, lack of harboured mammalian pathogens and possession of the machinery for eukaryotic post‐translational protein modification. So far, a variety of subunit vaccines, monoclonal antibodies and therapeutic proteins (antivirals) have been produced in plants as candidate countermeasures against emerging, reemerging and bioterrorism‐related infections. Many of these have been extensively evaluated in animal models and some have shown safety and immunogenicity in clinical trials. Here, we overview ongoing efforts to producing such plant‐based countermeasures.


title: New Isoxazolidine-Conjugates of Quinazolinones—Synthesis, Antiviral and Cytostatic Activity

text: A novel series of (3-diethoxyphosphoryl)isoxazolidines substituted at C5 with various quinazolinones have been synthesized by the 1,3-dipolar cycloaddition of N-methyl-C-(diethoxyphosphoryl)nitrone with N3-substitued 2-vinyl-3H-quinazolin-4-ones. All isoxazolidines were assessed for antiviral activity against a broad range of DNA and RNA viruses. Isoxazolidines trans-11f/cis-11f (90:10), trans-11h and trans-11i/cis-11i (97:3) showed weak activity (EC(50) = 6.84, 15.29 and 9.44 μM) toward VZV (TK(+) strain) which was only one order of magnitude lower than that of acyclovir used as a reference drug. Phosphonates trans-11b/cis-11b (90:10), trans-11c, trans-11e/cis-11e (90:10) and trans-11g appeared slightly active toward cytomegalovirus (EC(50) = 27–45 μM). Compounds containing benzyl substituents at N3 in the quinazolinone skeleton exhibited slight antiproliferative activity towards the tested immortalized cells with IC(50) in the 21–102 μM range.


title: OPEN TRACHEOSTOMY FOR COVID19 POSITIVE PATIENTS: A METHOD TO MINIMIZE AEROSOLIZATION AND REDUCE RISK OF EXPOSURE

text: INTRODUCTION: The COVID-19 virus is highly contagious and thus there is a potential of infecting operating staff when operating on these patients. This case series describes a method of performing open tracheostomy for COVID-19 patients while minimizing potential aerosolization of the virus using typically available equipment and supplies. METHODS: This is a case series of 18 patients who were COVID-19 positive and underwent open tracheostomy in the operating room under a negative pressure plastic hood created using readily available equipment and supplies. Patients had to be intubated for at least 14 days, be convalescing from their cytokine storm, and deemed to survive for at least 14 more days. Other indications for tracheostomy were altered mental status, severe deconditioning, respiratory failure and failed extubation attempts. RESULTS: There were 14 men and 4 women with severe SARS-CoV2 infection requiring long-term intubation since March 23 or later. The mean age was 61.7, BMI was 32.6, and the pre-tracheostomy ventilator day was 20.4. The indications for tracheostomy were altered mental status, severe deconditioning and continued respiratory with hypoxia. Failed extubation attempt rate was 16.7% and hemodialysis rate was 38.9%. All patients were hemodynamically stable, without any evidence of accelerating cytokine storm. To date there was one minor bleeding due to postoperative therapeutic anticoagulation. CONCLUSION: This report describes a method of performing open tracheostomy with minimal aerosolization using readily available equipment and supplies in most hospitals.


Screening for neurotropism of SARS-CoV-2 among COVID patients requiring neurosurgical interventions


title: Holy Immune Tolerance, Batman!

text: Bats are reservoir hosts of numerous viruses that cause severe pathology in humans. How bats cope with such pathogens remains elusive. In a recent issue of Cell, Pavlovich et al. (2018) describe several key adaptations in innate immune-related genes that suggest that the Egyptian rousette fruit bat relies on immune tolerance mechanisms to manage viral infections.


title: World braces for economic impact

text: The repercussions for businesses, workers and supply chains could be severe


title: Use of recombinant S1 spike polypeptide to develop a TCoV-specific antibody ELISA

text: Abstract Turkey coronavirus (TCoV) causes diarrhoea in young turkey poults but little is known about its prevalence in the field. To address this, a portion of the S1 region of the spike glycoprotein of TCoV carrying relevant B cell epitopes (amino acid positions 54–395) was cloned and expressed in Escherichia coli. This protein was purified and used to develop an indirect ELISA for detection of antibodies against TCoV. Using experimentally derived positive and negative turkey serum samples this ELISA showed high sensitivity (95%) and specificity (92%) for TCoV. To further evaluate the potential of the ELISA, 360 serum samples from commercial turkey farms in Ontario were tested for TCoV-specific antibodies using the recombinant TCoV ELISA. High seroprevalence of TCoV was found with 71.11% of breeders and 56.67% of meat turkeys testing seropositive. Although there was significant positive correlation with a TCoV-N protein-based ELISA, there was little to no correlation with the whole IBV antigen-based ELISA when field sera were tested for antibodies against TCoV.


title: Visitor behaviour and public health implications associated with exotic pet markets: an observational study

text: OBJECTIVES: To conduct on-site assessments of public health implications at key European pet markets. DESIGN: Observational study of visitor behaviour at stalls that displayed and sold animals, mainly amphibians and reptiles, to assess potential contamination risk from zoonotic pathogens. We noted initial modes of contact as ‘direct’ (handling animals) as well as ‘indirect’ (touching presumed contaminated animal-related sources) and observed whether these visitors subsequently touched their own head or mouth (H1), body (H2) or another person (H3). SETTING: Publicly accessible exotic animal markets in the UK, Germany and Spain. PARTICIPANTS: Anonymous members of the public in a public place. MAIN OUTCOME MEASURES: Occurrence and frequency of public contact (direct, indirect or no contact) with a presumed contaminated source. RESULTS: A total of 813 public visitors were observed as they attended vendors. Of these, 29 (3.6%) made direct contact with an animal and 222 (27.3%) made indirect contact with a presumed contaminated source, with subsequent modes of contact being H1 18.7%, H2 52.2% and H3 9.9%. CONCLUSIONS: Our observations indicate that opportunities for direct and indirect contact at pet markets with presumed contaminated animals and inanimate items constitute a significant and major concern, and that public attendees are exposed to rapid contamination on their person, whether or not these contaminations become associated with any episode of disease involving themselves or others. These public health risks appear unresolvable given the format of the market environment.


title: Discovery of anti‐SARS coronavirus drug based on molecular docking and database screening

text: The active site of 3CL proteinase (3CL(pro)) for coronavirus was identified by comparing the crystal structures of human and porcine coronavirus. The inhibitor of the main protein of rhinovirus (Ag7088) could bind with 3CL(pro) of human coronavirus, then it was selected as the reference for molecular docking and database screening. The ligands from two databases were used to search potential lead structures with molecular docking. Several structures from natural products and ACD‐SC databases were found to have lower binding free energy with 3CL(pro) than that of Ag7088. These structures have similar hydrophobicity to Ag7088. They have complementary electrostatic potential and hydrogen bond acceptor and donor with 3CL(pro), showing that the strategy of anti‐SARS drug design based on molecular docking and database screening is feasible.


Revisiting causality in psychosomatic research


title: A fractional-order model for the novel coronavirus (COVID-19) outbreak

text: The outbreak of the novel coronavirus (COVID-19), which was firstly reported in China, has affected many countries worldwide. To understand and predict the transmission dynamics of this disease, mathematical models can be very effective. It has been shown that the fractional order is related to the memory effects, which seems to be more effective for modeling the epidemic diseases. Motivated by this, in this paper, we propose fractional-order susceptible individuals, asymptomatic infected, symptomatic infected, recovered, and deceased (SEIRD) model for the spread of COVID-19. We consider both classical and fractional-order models and estimate the parameters by using the real data of Italy, reported by the World Health Organization. The results show that the fractional-order model has less root-mean-square error than the classical one. Finally, the prediction ability of both of the integer- and fractional-order models is evaluated by using a test data set. The results show that the fractional model provides a closer forecast to the real data.


title: Probable Role of Viruses in Calfhood Diseases

text: Abstract Bovine enteroviruses, bovine viral diarrhea virus, rotavirus (formerly called reovirus-like agent), coronavirus-like agent, bovine adenovirus, and bovine parainfluenza-3 virus have been isolated from calves suffering from neonatal disease. The experimental disease produced by these viruses is not necessarily severe or fatal, but under farm and ranch conditions, each probably serves as an added stress factor that contributes significantly to mortality from neonatal disease. After initial losses following the introduction of a virus into a herd, the subsequent losses will be limited because the cow will produce antibodies to protect the fetus during gestation. Antibodies will also be concentrated in colostrum to protect the calf at birth. However, colostrum must be fed immediately after birth, before the calf becomes infected.


title: Intermediate compartment (IC): from pre-Golgi vacuoles to a semi-autonomous membrane system

text: Despite its discovery more than three decades ago and well-established role in protein sorting and trafficking in the early secretory pathway, the intermediate compartment (IC) has remained enigmatic. The prevailing view is that the IC evolved as a specialized organelle to mediate long-distance endoplasmic reticulum (ER)–Golgi communication in metazoan cells, but is lacking in other eukaryotes, such as plants and fungi. However, this distinction is difficult to reconcile with the high conservation of the core machineries that regulate early secretory trafficking from yeast to man. Also, it has remained unclear whether the pleiomorphic IC components—vacuoles, tubules and vesicles—represent transient transport carriers or building blocks of a permanent pre-Golgi organelle. Interestingly, recent studies have revealed that the IC maintains its compositional, structural and spatial properties throughout the cell cycle, supporting a model that combines the dynamic and stable aspects of the organelle. Moreover, the IC has been assigned novel functions, such as cell signaling, Golgi-independent trafficking and autophagy. The emerging permanent nature of the IC and its connections with the centrosome and the endocytic recycling system encourage reconsideration of its relationship with the Golgi ribbon, role in Golgi biogenesis and ubiquitous presence in eukaryotic cells.


title: La grippe saisonnière

text: Résumé La grippe saisonnière est due aux virus influenza A et B. Il s’agit de virus enveloppés dont le génome est constitué de sept à huit fragments d’ARN. Les différents sous-types sont déterminés par la nature des deux glycoprotéines de surface HA et NA. La grippe saisonnière est une maladie épidémique et hivernale dans les zones à climat tempéré. Son épidémiologie est liée à la grande variabilité du virus au cours du temps, nécessitant la mise en place d’un système d’alerte détectant chaque année les variants circulants dominant et déterminant la composition vaccinale. Les symptômes cliniques de la grippe ne sont pas suffisamment spécifiques pour permettre le diagnostic sans examen virologique. Cela est particulièrement vrai en période non épidémique, chez les sujets de plus de 65 ans et chez les enfants de moins de cinq ans. L’enfant représente une cible privilégiée des infections à virus influenza. Le recours à l’hospitalisation est d’autant plus élevé que l’enfant est jeune. Chez le nourrisson, l’infection peut être paucisymptomatique et s’accompagner de manifestations non respiratoires (léthargie, convulsions, malaises). Le diagnostic virologique de la grippe est justifié chez tous les sujets hospitalisés pour un syndrome respiratoire compatible avec une infection à virus influenza. Il existe plusieurs outils permettant une recherche directe du virus dans les sécrétions respiratoires : isolement du virus en culture, détection d’antigènes, détection moléculaire de l’ARN. Le choix de la méthode se fait selon les caractéristiques du test : sensibilité, spécificité, rapidité et simplicité de réalisation, coût. Abstract Seasonal flu is caused by influenza viruses A and B. These enveloped viruses have a genome made up of seven or eight RNA fragments. The different subtypes are determined by the nature of the two surface glycoproteins HA and NA. Seasonal flu is an epidemic wintertime illness occurring in temperate climate zones. Its epidemiology is linked to the great variability of the virus in time, necessitating an alert system that detects dominating circulating variants each year and that determines the vaccination composition. Clinical flu symptoms are not sufficiently specific to allow for diagnosis with virological tests. This is especially true during non-epidemic periods as well as in subjects older than 65 and younger than five. Children are especially vulnerable to influenza virus infections. Hospitalization occurs more frequently, the younger the child. In children younger than two years, the infection can be pauci-symptomatic and is sometimes detected from non-respiratory symptoms such as lethargy, convulsions, and dizziness. In all cases of respiratory syndrome compatible with influenza virus infection in hospitalized subjects, virological flu diagnosis is of utmost interest. Several tools are available to allow for direct viral detection in respiratory specimens: cell culture isolation, antigenic detection, RNA molecular detection. Choice of method is based on the characteristics of the test: sensibility, specificity, speed and ease of realization, and cost.


title: Elevated interleukin‐6 is associated with severity of COVID‐19: a meta‐analysis

text: Coronavirus disease 2019 (COVID‐19) has spread rapidly around the world since its emergence in humans last December. Previous studies suggested that numerous markers of inflammation were elevated in patients in with severe disease relative to patients with milder conditions, and an elevated level of interleukin‐6 (IL‐6) was associated with a high case fatality of COVID‐19 infection. This article is protected by copyright. All rights reserved.


title: Constraints to cruising across cultures and time

text: Cruise tourism is permeating the global arena. With companies developing new ships/itineraries for the U.S. and China markets, understanding constraints to cruising for different cultures carries significant value for cruise tourism development. This study adopted longitudinal and cross-cultural approaches to validate constraint measures. Data were collected in the U.S. in 2008 and 2017 and in China in 2017, using the same set of constraint measures across different times and cultures. This multi-dimensional triangulation approach was deemed important for testing the robustness of a measurement scale and is believed to be the first of its type. Findings validate the cruising constraint instrument across time and cultures and provide theoretical and practical implications.


title: Chemical and Structural Aspects of Ebola Virus Entry Inhibitors

text: [Image: see text] The Ebolaviruses are members of the family Filoviridae (“filoviruses”) and cause severe hemhorragic fever with human case fatality rates as high as 90%. Infection requires attachment of the viral particle to cells and triggering of membrane fusion between the host and viral membranes, a process that occurs in the host endosome and is facilitated by the envelope glycoprotein (GP). One potential strategy for therapeutic intervention is the development of agents (antibodies, peptides, and small molecules) that can interfere with viral entry aspects such as attachment, uptake, priming, or membrane fusion. This paper highlights recent developments in the discovery and evaluation of therapeutic entry inhibitors and identifies opportunities moving forward.


title: La cellule d’aide à la Décision (CAD) « éléments et produits du corps humain » : définition, mode de fonctionnement et bilan en 2013-2014

text: La cellule d’aide à la décision « éléments et produits du corps humain » (CAD) est une structure qui se réunit en cas d’alerte épidémiologique pour émettre des recommandations sur les mesures à prendre pour prévenir la transmission par la transfusion ou par la greffe des agents infectieux non dépistés en routine (initialement Arboviroses puis Paludisme et infections à Coronavirus…). La CAD, pilotée par l’ANSM, comprend des experts et des représentants des institutions impliquées : ABM, CNR, ARS (CRH), CTSA, DGS, EFS, INTS et InVS. Les alertes sont adressées à l’ANSM par l’InVS. Au vu des éléments transmis, l’ANSM réunit la CAD afin de proposer des mesures pour les donneurs prélevés ou ayant séjourné dans les zones impactées par l’alerte. La discussion prend en compte notamment les données épidémiologiques disponibles, les mesures déjà en place localement et leur impact sur la mise à disposition des produits aux patients ainsi que les modalités de leur retrait en fin d’épidémie. Lors des alertes relatives à la Dengue, au Chikungunya ou au virus West Nile (WNV), la CAD est activée selon des critères préétablis tenant compte de la circulation virale antérieure en métropole, dans les DOM et à l’étranger. Les mesures applicables à la sélection des donneurs (exclusion), à la qualification des dons (dépistage supplémentaire) ou aux produits (quarantaine, inactivation) sont actualisées une fois par an mais l’opportunité de les appliquer est discutée pour chaque alerte. En 2013, la CAD a traité 21 alertes pour 16 mesures prises et 3 retraits de mesures. Depuis 2011, une liste des destinations motivant une exclusion a priori des donneurs, vis-à-vis du WNV, est établie en tenant compte des cas déclarés l’année précédente. Ainsi, un bilan détaillé des alertes traitées en 2013–2014 ainsi que l’efficacité de la stratégie adoptée pour le WNV en 2014 seront abordés. Les auteurs remercient tous les membres de la CAD pour leur implication dans son fonctionnement.


title: Presumptive Development of Fibrotic Lung Disease From Bordetella bronchiseptica and Post-infectious Bronchiolitis Obliterans in a Dog

text: A 7-month-old Miniature Poodle acquired from a pet store developed cough and subsequently respiratory distress compatible with Bordetella bronchiseptica infection. Partial but incomplete resolution of clinical signs and thoracic radiographic/computed tomographic imaging lesions were noted with use of susceptibility-guided antimicrobials. Additionally, a concern for an infectious nidus led to left cranial lung lobectomy at 9 months of age. Histopathology predominantly revealed polypoid and constrictive bronchiolitis obliterans (i.e., small airway disease). Intermittent antimicrobial administration over the next 5 years failed to blunt progressive clinical signs. At 8 years, necropsy confirmed severe airway-centered interstitial fibrosis. This pattern of fibrosis was strongly suggestive of underlying small airway disease as the trigger. In retrospect, post-infectious bronchiolitis obliterans (PIBO), a syndrome in young children caused by pulmonary infections but not yet recognized in pet dogs, likely initiated a pathway of fibrosis in this dog. In dogs with risk factors for community-acquired pathogens such as Bordetella bronchiseptica, PIBO is a differential diagnosis with development of severe, persistent respiratory signs incompletely responsive to appropriate antimicrobials. Untreated PIBO may lead to airway-centered interstitial fibrosis. Future study is required to determine if targeted therapy of PIBO could alter the course of end-stage pulmonary fibrosis.


title: The economic strategy for the Hong Kong SAR: Evidence from productivity and cost analysis

text: Abstract By using a growth accounting framework for the period 1980–2000, this paper estimates Hong Kong's total factor productivity and unit labor cost of twenty industries classified into three economic sectors of tradable goods, tradable services and non-tradable services. The results show that Hong Kong's total factor productivity has fallen in the 1990s. The competitiveness of the three sectors of tradable goods, tradable services and non-tradable services has increased, remained unchanged and declined, respectively in the last two decades. Policy recommendation for Hong Kong will be to aim for a supply-drive strategy so as to broaden the economic base.


title: Urban Trees in Times of Crisis: Palliatives, Mitigators, and Resources

text: Trees have been integral to cities for centuries. Their tangible and intangible benefits for human and environmental systems are particularly evident in times of crisis. As cities grow and adapt to climate change, historical, scientific, and practical expertise are needed to ensure equal access to urban trees and their benefits.


title: Controls of SARS-CoV-2 transmission in orthodontic practice

text: ABSTRACT The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has attracted worldwide concerns because of its high person-to-person infectivity and lethality, and it was labeled as a pandemic as the rapid increase of confirmed cases in most areas around the world became evident. The SARS-CoV-2 is mainly transmitted through respiratory droplets and close contact. There are also evidences of transmission through aerosols and digestive tracts. Since orthodontic treatment involves large population who need routine return-visits, it was significantly affected and suspended because of the COVID-19 pandemic and the shutdown of the dental clinics and hospitals. Although the spread of COVID-19 has been effectively controlled in China and many areas have gradually resumed work and classes, orthodontic participants are still under high risks of SARS-CoV-2 infection. This is due to the asymptomatic carriers of SARS-CoV-2 or patients in the incubation period may cause the cross infection between orthodontic practitioners and patients. The close proximity between the practitioners and the patients, and the generation of droplets and aerosols that contain saliva and blood during treatment further increase the risks of transmission. In this review, we summarized the preventive strategies for controls of SARS-CoV-2 transmission to protect both staffs and patients during the orthodontic practice.


title: Vulnerabilities in coronavirus glycan shields despite extensive glycosylation

text: Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential. Vaccine development has focussed on the principal target of the neutralizing humoral immune response, the spike (S) glycoprotein, which mediates receptor recognition and membrane fusion. Coronavirus S proteins are extensively glycosylated viral fusion proteins, encoding around 69-87 N-linked glycosylation sites per trimeric spike. Using a multifaceted structural approach, we reveal a specific area of high glycan density on MERS S that results in the formation of under-processed oligomannose-type glycan clusters, which was absent on SARS and HKU1 CoVs. We provide a comparison of the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin, where glycosylation plays a known role in shielding immunogenic epitopes. Consistent with the ability of the antibody-mediated immune response to effectively target and neutralize coronaviruses, we demonstrate that the glycans of coronavirus spikes are not able to form an efficacious high-density global shield to thwart the humoral immune response. Overall, our data reveal how differential organisation of viral glycosylation across class I viral fusion proteins influence not only individual glycan compositions but also the immunological pressure across the viral protein surface.


title: The Powerful Immune System Against Powerful COVID-19: A Hypothesis

text: Abstract On March 11, 2020, the World Health Organization declared the coronavirus outbreak a pandemic. Since December 2019, the world has experienced an outbreak of coronavirus disease 2019 (COVID-19). Epidemiology, risk factors, and clinical characteristics of patients with COVID-19 have been reported but the factors affecting the immune system against COVID-19 have not been well described. In this article, we provide a novel hypothesis to describe how an increase in cellular adenosine triphosphate (c-ATP) can potentially improve the efficiency of innate and adaptive immune systems to either prevent and fight off COVID-19.


title: Efficacy and safety of hydroxychloroquine as add-on therapy in uncontrolled type 2 diabetes patients who were using two oral antidiabetic drugs

text: OBJECTIVE: To evaluate the Safety and Efficacy of Hydroxychloroquine as add-on therapy in uncontrolled type 2 diabetes patients who were using two oral antidiabetic drugs. MATERIALS AND METHODS: This was a double blind, placebo controlled, parallel group study in 304 inadequately controlled type 2 diabetes (T2DM) subjects with two oral antidiabetic drugs (glimepiride 4 mg and metformin 500 mg) were randomised to hydroxychloroquine (HCQ) 200 mg, 300 mg, 400 mg once daily (OD) or placebo. Dose of hydroxychloroquine was selected as per body weight of the subject. Primary end point was glycated haemoglobin (HbA1c) change at week 12 from baseline. Secondary endpoint was change in fasting plasma glucose (FPG), post prandial plasma glucose (PPG), body weight and any adverse reaction including no of hypoglycemic events, as well as a change in the percentage of subjects with A1C < 7.0% and > 6.5% after 12 weeks of treatment.. In follow-up of 400 mg once daily was once again divided to 200 mg twice daily (BD) to study the effect on tolerability profile for further 12 weeks. RESULTS: Hydroxychloroquine was associated with significant reduction in HbA1c from baseline (7–8.5%) in 12 weeks −0.78%, −0.91% and 1.2% for hydroxychloroquine 200 mg, 300 mg and 400 mg OD, respectively, versus 0.13% with placebo (P < 0.005). FPG and PPG were reduced by −25 to −38 mg/dl and 34–53 mg/dl, respectively. Body weight also reduced in each group of HCQ. Hypoglycemia was reported only with 300 mg (1.2%) and 400 mg (2.1%) group of HCQ. It was observed that patients who complains with mild GI disturbance with HCQ 400 mg glycemic efficacy was maintained with 200 mg BD with significant relief of the symptoms. CONCLUSION: Hydroxychloroquine added to sulphonylurea and metformin, improves glycemic control significantly in T2DM patients. Glycemic effect of different dose of hydroxychloroquine is dose dependent. The safety/tolerability profile of hydroxychloroquine was favourable except GI disturbance which is more frequent with 400 mg. This can be avoided with 200 mg BD without compromise on efficacy.


title: European biosafety labs set to grow

text: Bioterrorism and emerging diseases spur building boom, although some question the need for more facilities.


title: Complete genome sequence analysis of chicken astrovirus isolate from India

text: OBJECTIVE: Chicken astroviruses have been known to cause severe disease in chickens leading to increased mortality and “white chicks” condition. Here we aim to characterize the causative agent of visceral gout suspected for astrovirus infection in broiler breeder chickens. METHODS: Total RNA isolated from allantoic fluid of SPF embryo passaged with infected chicken sample was sequenced by whole genome shotgun sequencing using ion-torrent PGM platform. The sequence was analysed for the presence of coding and non-coding features, its similarity with reported isolates and epitope analysis of capsid structural protein. RESULTS: The consensus length of 7513 bp genome sequence of Indian isolate of chicken astrovirus was obtained after assembly of 14,121 high quality reads. The genome was comprised of 13 bp 5′-UTR, three open reading frames (ORFs) including ORF1a encoding serine protease, ORF1b encoding RNA dependent RNA polymerase (RdRp) and ORF2 encoding capsid protein, and 298 bp of 3′-UTR which harboured two corona virus stem loop II like “s2m” motifs and a poly A stretch of 19 nucleotides. The genetic analysis of CAstV/INDIA/ANAND/2016 suggested highest sequence similarity of 86.94% with the chicken astrovirus isolate CAstV/GA2011 followed by 84.76% with CAstV/4175 and 74.48%% with CAstV/Poland/G059/2014 isolates. The capsid structural protein of CAstV/INDIA/ANAND/2016 showed 84.67% similarity with chicken astrovirus isolate CAstV/GA2011, 81.06% with CAstV/4175 and 41.18% with CAstV/Poland/G059/2014 isolates. However, the capsid protein sequence showed high degree of sequence identity at nucleotide level (98.64-99.32%) and at amino acids level (97.74–98.69%) with reported sequences of Indian isolates suggesting their common origin and limited sequence divergence. The epitope analysis by SVMTriP identified two unique epitopes in our isolate, seven shared epitopes among Indian isolates and two shared epitopes among all isolates except Poland isolate which carried all distinct epitopes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11259-016-9673-6) contains supplementary material, which is available to authorized users.


Toulouse Alzheimer’s Clinical Research Center Recovery after the COVID-19 Crisis: Telemedicine an Innovative Solution for Clinical Research during the Coronavirus Pandemic


title: Susceptibility to cytotoxic T lymphocyte-induced apoptosis is a function of the proliferative status of the target

text: Cytotoxic T lymphocytes (CTL) kill cells by perturbing the target's plasma membrane and by inducing the disintegration of the target cell's DNA into oligonucleosomal fragments, a process characteristic of apoptosis. We show that the DNA fragmentation event is distinct from the membrane lysis event and is dependent on the state of target cell activation or commitment into the mitotic cycle. Quiescent cells were refractory to DNA fragmentation, but not to membrane lysis. Log phase growth, transformation with c-myc, or infection of quiescent G0 targets with herpes simplex virus-1, which induces a competent state for DNA synthesis, all enhanced target cell susceptibility to CTL-induced DNA fragmentation without altering the membrane lysis. These results suggest that G0 cells are resistant to CTL-induced apoptosis, but that entry into G1 or a G1-like state by growth factors, cellular transformation, or DNA virus infection renders them competent to enter the apoptotic pathway(s).


title: Seasonality of infectious diseases and severe acute respiratory syndrome–what we don't know can hurt us

text: Summary The novel severe acute respiratory syndrome (SARS) coronavirus caused severe disease and heavy economic losses before apparently coming under complete control. Our understanding of the forces driving seasonal disappearance and recurrence of infectious diseases remains fragmentary, thus limiting any predictions about whether, or when, SARS will recur. It is true that most established respiratory pathogens of human beings recur in wintertime, but a new appreciation for the high burden of disease in tropical areas reinforces questions about explanations resting solely on cold air or low humidity. Seasonal variation in host physiology may also contribute. Newly emergent zoonotic diseases such as ebola or pandemic strains of influenza have recurred in unpredictable patterns. Most established coronaviruses exhibit winter seasonality, with a unique ability to establish persistent infections in a minority of infected animals. Because SARS coronavirus RNA can be detected in the stool of some individuals for at least 9 weeks, recurrence of SARS from persistently shedding human or animal reservoirs is biologically plausible.


title: Acute increase in deaths among adult congenital heart disease patients during COVID-19 - single center experience.

text: Abstract Fear of acquiring severe acute respiratory syndrome coronavirus 2 infection is a major contributor to under-utilization of the healthcare system during the current pandemic. In this report, we describe 4 cases of unexpected deaths that occurred within a short time period in adult congenital heart disease patients without warning symptoms.


MP17-08 NEUROGENIC BLADDER DYSFUNCTION IN A MURINE MODEL OF MULTIPLE SCLEROSIS IS CAUSED BY CORONOVIRUS-INDUCED DEMYELINATION OF THE NERVOUS SYSTEM


title: The other rabies viruses: The emergence and importance of lyssaviruses from bats and other vertebrates

text: Summary The recognition that viruses related to rabies virus cause rabies in humans has stimulated research into the relationships, geographic distribution and natural histories of these viruses. This paper reviews what is known of these fascinating viruses and the complexity of prevention and treatment of the disease they cause.


Mesenchymal stem cells represent a potential therapeutic option for coronavirus disease 2019-related acute respiratory distress syndrome


title: Increasing diversity of swine parvoviruses and their epidemiology in African pigs

text: Abstract Detection of infectious viral agents has been on the increase globally with the advent and usage of more sensitive and selective novel molecular techniques in the epidemiological study of viral diseases of economic importance to the swine industry. The observation is not different for the pig-infecting member of the subfamily Parvovirinae in the family Parvoviridae as the application of novel molecular methods like metagenomics has brought about the detection of many other novel members of the group. Surprisingly, the list keeps increasing day by day with some of them possessing zoonotic potentials. In the last one decade, not less than ten novel swine-infecting viruses have been added to the subfamily, and ceaseless efforts have been in top gear to determine the occurrence and prevalence of the old and new swine parvoviruses in herds of pig-producing countries worldwide. The story, however, is on the contrary on the African continent as there is presently a dearth of information on surveillance initiatives of the viruses among swine herds of pig-producing countries in the region. Timely detection and characterization of the viral pathogens is highly imperative for the implementation of effective control and prevention of its spread. This review therefore presents a concise overview on the epidemiology of novel porcine parvoviruses globally and also provides up-to-date highlights on the reported cases of the viral agents in the African sub-region.


title: Lanxess withstands challenging environment in 2019, achieves record margin

text: German speciality chemicals company Lanxess AG reports that it had a ‘successful fiscal year’ in 2019 despite the increasingly difficult global economic environment. It generated EBITDA pre-exceptionals of E1.019 billion and net income from continuing operations of E240 million on net sales of E6.802 billion. The EBITDA margin pre-exceptionals for full-year 2019 increased to 15.0% compared to 14.4% for the previous year, a new record high for the company.


title: The potential use of thalidomide in the therapy of graft-versus-host disease—A review of clinical and laboratory information

text: Abstract This article reviews the historical development of thalidomide as an immunosuppressive agent and the current state of knowledge of thalidomide as an anti-graft-versus-host disease (GVHD) agent. The evidence suggests that metabolites of thalidomide act at an early stage in the antigen recognition-activation pathway of graft T lymphocytes and down regulate normal lymphocyte responses. This effect seems to have beneficial effects in both acute and chronic GVHD, but the optimal mode of use in the clinical setting remains to be determined.


title: The clinical benefits of Chinese patent medicines against COVID-19 based on current evidence

text: Abstract The outbreak of emerging infectious pneumonia caused by 2019 Novel Coronavirus (2019-nCoV) has posed an enormous threat to public health, and traditional Chinese medicine (TCM) have made vast contribution to the prevention, treatment and rehabilitation of coronavirus disease 19 (COVID-19) among Chinese population. As an indispensable part of TCM, Chinese patent medicines (CPMs) are highly valued and critically acclaimed in their campaign to contain and tackle the epidemic, they can achieve considerable effects for both suspected cases under medical observation period, and confirmed individuals with serious underlying diseases or critical conditions. Given this, based on the Guideline on Diagnosis and Treatment of Coronavirus Disease 2019 in China, the present review summarized the basic information, clinical evidence and published literatures of recommended CPMs against COVID-19. The details were thoroughly introduced involving compositions, therapeutic effects, clinical indications, medication history of CPMs and the profiles of corresponding research. With regard to infected patients with different stages and syndrome, the preferable potentials and therapeutic mechanism of CPMs were addressed through the comprehensive collection of relevant literatures and on-going clinical trials. This study could provide an insight into clinical application and underlying mechanism of recommended CPMs against COVID-19, with the aim to share the Chinese experience in clinical practice and facilitate scientific development of TCM, especially CPMs in the fierce battle of COVID-19.


title: Authors’ reply to correspondence in response to “Will children reveal their secret? The coronavirus dilemma”

text: The role of ACE2 receptor in SARS-CoV-2 infection and in COVID-19 outcomes is still debated, especially in children.


title: Identification of a recombinant dengue virus type 1 with 3 recombination regions in natural populations in Guangdong province, China

text: Using recombination analysis, we identified a recombinant dengue virus type 1 strain, namely, GD23/95, with three recombination regions, located within the sequences of the prM/E junction, NS1, and NS3, respectively. The recombinant dengue virus was further confirmed by phylogenetic analysis based on its recombination and non-recombination regions. This appears to be the first study to confirm the existence of three recombination regions in a single dengue virus isolate and to report recombination between parent virus strains isolated from the same geographic area (Guangdong province, China). It is also the first to report breakpoints within the NS3 gene of dengue viruses.


title: Detecting Food‐ and Waterborne Viruses by Surface‐Enhanced Raman Spectroscopy

text: Abstract: Food‐ and waterborne viruses pose serious health risks to humans and were associated with many outbreaks worldwide. Rapid, accurate, and nondestructive methods for detection of viruses are of great importance to protect public health. In this study, surface‐enhanced Raman spectroscopy (SERS) coupled with gold SERS‐active substrates was used to detect and discriminate 7 food‐ and waterborne viruses, including norovirus, adenovirus, parvovirus, rotavirus, coronavirus, paramyxovirus, and herpersvirus. Virus samples were purified and dialyzed in phosphate buffered saline (8 to 9 log PFU/mL) and then further diluted in deionized water for SERS measurement. After capturing the characteristic SERS spectral patterns, multivariate statistical analyses, including soft independent modeling of class analogy (SIMCA) and principal component analysis (PCA), were employed to analyze SERS spectral data for characterization and identification of viruses. The results show that SIMCA was able to differentiate viruses with and without envelope with >95% of classification accuracy, while PCA presented clear spectral data segregations between different virus strains. The virus detection limit by SERS using gold substrates reached a titer of 10(2). Practical Application: SERS is a simple, rapid, and accurate method for detection of food‐ and waterborne viruses. Our results demonstrate that coupled with gold substrates, SERS was able to rapidly detect and discriminate among different food‐ and waterborne viruses, indicating that SERS can provide rapid, sensitive, and reproducible detection results with minimum sample preparation for virus detection.


title: Chapter 8 Transportation and _______

text: Abstract This chapter examines some topics that have not received as much attention, at least not concerning the potential roles for transportation in mitigating or avoiding public health impacts.


title: COVID‐19 presenting with immune thrombocytopenia: a case report and review of the literature

text: Novel coronavirus disease (COVID‐19) may be associated with thrombocytopenia which might have different mechanisms in different patients and in different phases of the disease. Cytokine release, thrombotic consumption or autoimmune destruction are some leading etiologies of thrombocytopenia in COVID‐19. This case report presents a 41‐year‐old male COVID‐19 patient who had petechiae and purpura as the referral symptoms. Laboratory tests revealed isolated thrombocytopenia with no other additional pathologic findings. Most probable diagnosis was COVID‐19 induced immune thrombocytopenia (ITP) and high dose intravenous immunoglobulin (IVIg) treatment generated a good response. There were four other recent publications with a total of eight cases in the literature. The presented case was discussed in comparison with those similar cases. This article is protected by copyright. All rights reserved.


title: Synthesis and anti‐coronavirus activity of a series of 1‐thia‐4‐azaspiro[4.5]decan‐3‐one derivatives

text: A series of 1‐thia‐4‐azaspiro[4.5]decan‐3‐ones bearing an amide group at C‐4 and various substitutions at C‐2 and C‐8 were synthesized and evaluated against human coronavirus and influenza virus. Compounds 7m, 7n, 8k, 8l, 8m, 8n, and 8p were found to inhibit human coronavirus 229E replication. The most active compound was N‐(2‐methyl‐8‐tert‐butyl‐3‐oxo‐1‐thia‐4‐azaspiro[4.5]decan‐4‐yl)‐3‐phenylpropanamide (8n), with an EC(50) value of 5.5 µM, comparable to the known coronavirus inhibitor, (Z)‐N‐[3‐[4‐(4‐bromophenyl)‐4‐hydroxypiperidin‐1‐yl]‐3‐oxo‐1‐phenylprop‐1‐en‐2‐yl]benzamide (K22). Compound 8n and structural analogs were devoid of anti‐influenza virus activity, although their scaffold is shared with a previously discovered class of H3 hemagglutinin‐specific influenza virus fusion inhibitors. These findings point to the 1‐thia‐4‐azaspiro[4.5]decan‐3‐one scaffold as a versatile chemical structure with high relevance for antiviral drug development.


title: Genetics of mouse hepatitis virus transcription: Identification of cistrons which may function in positive and negative strand RNA synthesis

text: Abstract A panel of 26 temperature-sensitive mutants of MHV-A59 were selected by mutagenesis with either 5-fluorouracil or 5-azacytidine. Complementation analysis revealed the presence of one RNA+ and five RNA− complementation groups. None of the RNA− complementation groups transcribed detectable levels of positive- or negative-stranded RNA at the restrictive temperature. Temperature shift experiments after the onset of mRNA synthesis revealed at least two classes of RNA− mutants. RNA− complementation groups A, B, D, and E were blocked in the ability to release infectious virus and transcribe mRNA and genome, while group C mutants continued to release infectious virus and transcribe both mRNA and genome. Temperature shift experiments at different times postinfection suggest that the group C mutants encode a function required early in viral transcription which affects the overall rate of positive strand synthesis. Analysis of steady state levels of negative strand RNA after the shift indicate that the group C mutants were probably blocked in the ability to synthesize additional minus strand RNA under conditions in which the group E mutants continued low levels of minus strand synthesis. These data suggest that at least four cistrons may be required for positive strand synthesis while the group C cistron functions during minus strand synthesis.


title: Politics of Prevention: Reflections From the COVID-19 Pandemic

text: The COVID-19 pandemic from a prevention science perspective, including research topics, is discussed. Political considerations that influence prevention activities, with examples from the pandemic and from more typical prevention initiatives in schools and communities, are presented. The definitions of prevention science and prevention interventions are delineated, and a brief summary of prevention history is given. The relationship between health disparities and COVID-19 is discussed. Two theoretical perspectives that may help to inform effectiveness of COVID-19 prevention measures, Health Belief Model and Theory of Reasoned Action and Planned Behavior, are summarized. The article emphasizes the importance of adapting prevention applications to the intended recipients, especially ethnic and cultural groups. The need to strengthen prevention training in graduate education and strategies to reform the education to meet accreditation and licensing standards are suggested.