title: Attaching-effacing Escherichia coli Infections in Cattle

text: Diarrheagenic Escherichia coli are now broadly placed into 6 classes based on virulence mechanisms. One of these classes, enterotoxigenic E coli, is the most common cause of diarrhea in beef and dairy calves in the first 4 days of life. Two other diarrheagenic classes, enterohemorrhagic E coli (EHEC) and enteropathogenic E coli (EPEC), are important causes of disease in human beings, but less well substantiated causes of diarrhea in calves. E coli strains that cause hemorrhagic colitis and hemolytic uremic syndrome in humans, express high levels of Shiga toxin, cause attaching-effacing (A/E) lesions in intestinal epithelial cells, and possess a specific 60-MDa EHEC plasmid are known as EHEC. One feature EHEC and EPEC have in common is the causation of intestinal epithelial lesions known as attaching and effacing (A/E). Attaching-effacing E coli (AEEC) is a designation for those E coli strains known to cause A/E lesions or at least carry the genes for this trait, and therefore include organisms that fall into either the EHEC or EPEC classes. Because cattle are carriers of many different serotypes of EHEC, much emphasis has been placed on the public health and food safety concerns associated with the fecal shedding of these organisms. However, much less emphasis has been given to their roles as diarrheagenic pathogens of cattle. The goal of this article is to address the question of pathogenicity, with a review that focuses on the results of studies of natural and experimental infections with these organisms. The authors conclude that there is overwhelming evidence that many different serogroups of AEEC are diarrheagenic pathogens of calves.


title: Infectious agents and age-related neurodegenerative disorders

text: Abstract As with other organ systems, the vulnerability of the nervous system to infectious agents increases with aging. Several different infectious agents can cause neurodegenerative conditions, with prominent examples being human immunodeficiency virus (HIV-1) dementia and prion disorders. Such infections of the central nervous system (CNS) typically have a relatively long incubation period and a chronic progressive course, and are therefore increasing in frequency as more people live longer. Infectious agents may enter the central nervous system in infected migratory macrophages, by transcytosis across blood–brain barrier cells or by intraneuronal transfer from peripheral nerves. Synapses and lipid rafts are important sites at which infectious agents may enter neurons and/or exert their cytotoxic effects. Recent findings suggest the possibility that infectious agents may increase the risk of common age-related neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and stroke. While scenarios can be envisioned whereby viruses such as Chlamydia pneumoniae, herpes simplex and influenza promote damage to neurons during aging, there is no conclusive evidence for a major role of these pathogens in neurodegenerative disorders. In the case of stroke, blood vessels may be adversely affected by bacteria or viruses resulting in atherosclerosis.


SARS control: First nasal vaccine effective in monkeys


title: Post-infectious encephalitis in adults: Diagnosis and management

text: Summary Many important central nervous system (CNS) syndromes can develop following microbial infections. The most severe forms of post-infectious encephalitis include acute disseminated encephalomyelitis (ADEM), acute hemorrhagic leukoencephalitis and Bickerstaff's brainstem encephalitis. ADEM is an inflammatory demyelinating disorder of the CNS. It typically follows a minor infection with a 2–30 days latency period and is thought to be immune-mediated. It is clinically characterized by the acute onset of focal neurological signs and encephalopathy. Patients can require intensive care unit admission because of coma, seizures or tetraplegia. Cerebrospinal fluid analysis usually shows lymphocytic pleocytosis but, unlike viral or bacterial encephalitis, no evidence of direct CNS infection is found. There are no biologic markers of the disease and cerebral magnetic resonance imaging is essential to diagnosis, detecting diffuse or multifocal asymmetrical lesions throughout the white matter on T2- and FLAIR-weighted sequences. High-dose intravenous steroids are accepted as first-line therapy and beneficial effects of plasma exchanges and intravenous immunoglobulins have also been reported. Outcome of ADEM is usually favorable but recurrent or multiphasic forms have been described.


title: Neonatal encephalopathy therapy optimization for better neuroprotection with inhalation of CO(2): the HENRIC feasibility and safety trial

text: BACKGROUND: There is an association between hypocapnia and adverse neurodevelopmental outcome in infants with neonatal encephalopathy (NE). Our aim was to test the safety and feasibility of 5% CO(2) and 95% air inhalation to correct hypocapnia in mechanically ventilated infants with NE undergoing therapeutic hypothermia. METHODS: Ten infants were assigned to this open-label, single-center trial. The gas mixture of 5% CO(2) and 95% air was administered through patient circuits if the temperature-corrected PCO(2) ≤40 mm Hg. The CO(2) inhalation was continued for 12 h or was stopped earlier if the base deficit (BD) level decreased <5 mmol/L. Follow-up was performed using Bayley Scales of Infant Development II. RESULTS: The patients spent a median 95.1% (range 44.6–98.5%) of time in the desired PCO(2) range (40–60 mm Hg) during the inhalation. All PCO(2) values were >40 mm Hg, the lower value of the target range. Regression modeling revealed that BD and lactate had a tendency to decrease during the intervention (by 0.61 and 0.55 mmol/L/h, respectively), whereas pH remained stable. The rate of moderate disabilities and normal outcome was 50%. CONCLUSIONS: Our results suggest that inhaled 5% CO(2) administration is a feasible and safe intervention for correcting hypocapnia.


title: Isotype-specific antibody responses to bovine herpesvirus 1 in sera and mucosal secretions of calves after experimental reinfection and after reactivation

text: Abstract Isotype-specific antibody responses to bovine herpesvirus 1 (BHV1) were measured in sera, nasal, ocular and genital secretions of calves that were reinfected with BHV1 and 6 weeks later treated with corticosteroids to reactivate putative latent virus. After reinfection and after reactivation, no BHV1-specific IgM antibody response was detected. The serum IgA response was only transiently detectable after reinfection and again appeared rapidly after reactivation in most calves. Most calves showed an increase in nasal and ocular IgA titres after reinfection and reactivation; some calves also had IgA antibodies in genital secretions. A salient finding was that after reinfection and reactivation more calves showed a serum IgA response than virus shedding or an increase in serum IgG1 or IgG2 titres. This suggests that the serum IgA response would be the most sensitive indicator to detect BHV1 reinfection and reactivation. No correlation was found between nasal IgA titre at the time of reinfection or corticosteroid treatment and the period of virus shedding, suggesting that nasal IgA does not play a major role in protection against reinfection with BHV1.


title: Virus–virus interactions impact the population dynamics of influenza and the common cold

text: The human respiratory tract hosts a diverse community of cocirculating viruses that are responsible for acute respiratory infections. This shared niche provides the opportunity for virus–virus interactions which have the potential to affect individual infection risks and in turn influence dynamics of infection at population scales. However, quantitative evidence for interactions has lacked suitable data and appropriate analytical tools. Here, we expose and quantify interactions among respiratory viruses using bespoke analyses of infection time series at the population scale and coinfections at the individual host scale. We analyzed diagnostic data from 44,230 cases of respiratory illness that were tested for 11 taxonomically broad groups of respiratory viruses over 9 y. Key to our analyses was accounting for alternative drivers of correlated infection frequency, such as age and seasonal dependencies in infection risk, allowing us to obtain strong support for the existence of negative interactions between influenza and noninfluenza viruses and positive interactions among noninfluenza viruses. In mathematical simulations that mimic 2-pathogen dynamics, we show that transient immune-mediated interference can cause a relatively ubiquitous common cold-like virus to diminish during peak activity of a seasonal virus, supporting the potential role of innate immunity in driving the asynchronous circulation of influenza A and rhinovirus. These findings have important implications for understanding the linked epidemiological dynamics of viral respiratory infections, an important step towards improved accuracy of disease forecasting models and evaluation of disease control interventions.


title: Variations in Spike Glycoprotein Gene of MERS-CoV, South Korea, 2015

text: An outbreak of nosocomial infections with Middle East respiratory syndrome coronavirus occurred in South Korea in May 2015. Spike glycoprotein genes of virus strains from South Korea were closely related to those of strains from Riyadh, Saudi Arabia. However, virus strains from South Korea showed strain-specific variations.


title: A functional subset of CD8(+) T cells during chronic exhaustion is defined by SIRPα expression

text: Prolonged exposure of CD8(+) T cells to antigenic stimulation, as in chronic viral infections, leads to a state of diminished function termed exhaustion. We now demonstrate that even during exhaustion there is a subset of functional CD8(+) T cells defined by surface expression of SIRPα, a protein not previously reported on lymphocytes. On SIRPα(+) CD8(+) T cells, expression of co-inhibitory receptors is counterbalanced by expression of co-stimulatory receptors and it is only SIRPα(+) cells that actively proliferate, transcribe IFNγ and show cytolytic activity. Furthermore, target cells that express the ligand for SIRPα, CD47, are more susceptible to CD8(+) T cell-killing in vivo. SIRPα(+) CD8(+) T cells are evident in mice infected with Friend retrovirus, LCMV Clone 13, and in patients with chronic HCV infections. Furthermore, therapeutic blockade of PD-L1 to reinvigorate CD8(+) T cells during chronic infection expands the cytotoxic subset of SIRPα(+) CD8(+) T cells.


title: Rooting Trees, Methods for

text: Abstract Identifying the root of a phylogenetic tree is important because incorrectly rooted phylogenetic trees may mislead evolutionary and taxonomic inferences. Many techniques for inferring the root have been proposed, but each has shortcomings that may make it inappropriate for any particular dataset. Here we outline the various ways to root phylogenetic trees, which include: outgroup, midpoint rooting, molecular clock rooting, and Bayesian molecular clock rooting. In addition, we discuss the pros and cons and also list software availability for each of the rooting methods.


title: Characterization of a membrane‐bound aminopeptidase purified from Acyrthosiphon pisum midgut cells: A major binding site for toxic mannose lectins

text: A single membrane‐bound aminopeptidase N (APN) occurs in the pea aphid (Acyrthosiphon pisum Harris) midgut, with a pH optimum of 7.0, pI of 8.1 and molecular mass of 130 kDa. This enzyme accounts for more than 15.6% of the total gut proteins. After being solubilized in detergent, APN was purified to homogeneity. The enzyme is a glycoprotein rich in mannose residues, which binds the entomotoxic lectins of the concanavalin family. The internal sequence of APN is homologous with a conservative domain in APNs, and degenerated primers of highly conserved APN motifs were used to screen a gut cDNA library. The complete sequence of APN has standard residues involved in zinc co‐ordination and catalysis and a glycosyl‐phosphatidylinositol anchor, as in APNs from Lepidoptera. APN has a broad specificity towards N‐terminal amino acids, but does not hydrolyze acidic aminoacyl‐peptides, thus resembling the mammalian enzyme (EC 3.4.11.2). The k (cat)/K (m) ratios for different di‐, tri‐, tetra‐, and penta‐peptides suggest a preference for tripeptides, and that subsites S(1), S(2)′ and S(3)′ are pockets able to bind bulky aminoacyl residues. Bestatin and amastatin bound APN in a rapidly reversible mode, with K (i) values of 1.8 µm and 0.6 µm, respectively. EDTA inactivates this APN (k (obs) 0.14 m (−1)·s(−1), reaction order of 0.44) at a rate that is reduced by competitive inhibitors. In addition to oligopeptide digestion, APN is proposed to be associated with amino‐acid‐absorption processes which, in contrast with aminopeptidase activity, may be hampered on lectin binding.


title: A germ-free status does not protect from the lethal effects of acute lung damage caused by o,s,s,-trimethyl phosphorodithioate

text: Abstract To investigate whether a normal resident microbiological flora of conventional rats influences the lethality of chemical-induced lung damage, the pneumotoxin O,S,S-trimethyl phosphorodithioate (OSSMe, 75 or 100 mg/kg, s.c.) was administered to age-matched conventional and germ-free male F344 rats. Microbiological and serological examinations confirmed the germ-free state of the germ-free rats and showed that no specific lung pathogens were present in the conventional rats. As in conventional rats, clinical symptoms and death of OSSMe-treated germ-free rats resulted from respiratory failure. The germ-free rats were not more resistant, but rather more susceptible to OSSMe than conventional rats. Increases in lung weight and histological examination of lung tissue 3 days after dosing with OSSMe (75 mg/kg, s.c.) showed no differences between germ-free and conventional rats. Despite alterations in their nasopharyngeal flora, death in the conventional rats was probably not caused by bacterial superinfection. The higher susceptibility of germ-free rats to OSSMe can be partly attributed to pharmacokinetic differences, since plasma levels of OSSMe decreased more slowly in germ-free than in conventional rats. It is concluded that germ-free rats are not protected from the lethal consequences of acute chemical-induced lung damage.


title: Novel avian single-chain fragment variable (scFv) targets dietary gluten and related natural grain prolamins, toxic entities of celiac disease

text: BACKGROUND: Celiac disease (CD) is a chronic, small intestinal inflammatory disease mediated by dietary gluten and related prolamins. The only current therapeutic option is maintenance of a strict life-long gluten-free diet, which implies substantial burden for CD patients. Different treatment regimes might be feasible, including masking of toxic celiac peptides with blocking antibodies or fragments thereof. The objective of this study was therefore to select and produce a recombinant avian single-chain fragment variable (scFv) directed against peptic-tryptic digested gliadin (PT-Gliadin) and related celiac toxic entities. RESULTS: Gluten-free raised chicken of same age were immunized with PT-Gliadin. Chicken splenic lymphocytes, selected with antigen-coated magnetic beads, served as RNA source for the generation of cDNA. Chicken V(H) and V(L) genes were amplified from the cDNA by PCR to generate full-length scFv constructs consisting of V(H) and V(L) fragments joined by a linker sequence. ScFv constructs were ligated in a prokaryotic expression vector, which provides a C-terminal hexahistidine tag. ScFvs from several bacterial clones were expressed in soluble form and crude cell lysates screened for binding to PT-Gliadin by ELISA. We identified an enriched scFv motif, which showed reactivity to PT-Gliadin. One selected scFv candidate was expressed and purified to homogeneity. Polyclonal anti-PT-Gliadin IgY, purified from egg yolk of immunized chicken, served as control. ScFv binds in a dose-dependent manner to PT-Gliadin, comparable to IgY. Furthermore, IgY competitively displaces scFv from PT-Gliadin and natural wheat flour digest, indicating a common epitope of scFv and IgY. ScFv was tested for reactivity to different gastric digested dietary grain flours. ScFv detects common and khorasan wheat comparably with binding affinities in the high nanomolar range, while rye is detected to a lesser extent. Notably, barley and cereals which are part of the gluten-free diet, like corn and rice, are not detected by scFv. Similarly, the pseudo-grain amaranth, used as gluten-free alternative, is not targeted by scFv. This data indicate that scFv specifically recognizes toxic cereal peptides relevant in CD. CONCLUSION: ScFv can be of benefit for future CD treatment regimes.


title: ANOSMIA - A REVIEW: IN THE CONTEXT OF COVID 19/OROFACIAL PAIN

text: ABSTRACT Background Anosmia/hyposmia is a relatively rare sensory disorder that could indicate an underlying more serious cause. In the context of the current COVID 19 pandemic, this could be one of the red flags for the dental practitioner in terms of screening potential COVID 19 patients. Methods The authors searched electronic databases with regards to anosmia/hyposmia and their relation to local and systemic causes. Results The authors found articles relating to the physiology and significance of normal olfaction, etiology, and pathophysiology of olfaction and disorders of the same. Also, we found the most recent literature of anosmia/hyposmia linked to early symptoms of this pandemic. Conclusions Anosmia/hyposmia is most likely indicative of a local or systemic pathology affecting the olfactory system. Recent evidence suggests the importance of this as related to the new global pandemic of COVID 19. Practical Implications The dental professional must be cognizant of the fact that anosmia/hyposmia could indicate a more serious underlying local or systemic issue. In the coming months of the new reality of COVID 19, dental practitioners have an additional role of potential early screening of these infections.


title: Diagnóstico microbiológico de la colonización-infección broncopulmonar en el paciente con fibrosis quística

text: Cystic fibrosis (CF), a condition produced by mutations in the gene that encodes the cystic fibrosis transmembrane conductance regulator, is the most prevalent autosomal-recessive hereditary disease in caucasian populations. Among other repercussions, this defect leads to an alteration of respiratory secretions and determines a predisposition for chronic bronchopulmonary colonization-infection, which is the main driver of the high morbidity and early mortality of CF patients. Colonization by Staphylococcus aureus and Haemophilus influenzae is frequent in children younger than 10 years, but mucoid Pseudomonas aeruginosa is by far the most relevant pathogen in adults with CF and is responsible for the progressive bronchopulmonary deterioration. As a consequence of repeated, long-lasting antimicrobial treatments and deterioration of lung function, colonization by multidrug-resistant Gram-negative bacilli, such as Stenotrophomonas maltophilia, Achromobacter spp. and Burkholderia cepacia complex, is also frequent in adult CF patients. The special characteristics of the pathologic process and the microorganisms implicated in CF make it advisable to consider microbiological follow-up of chronic bronchopulmonary colonization-infection in these patients a specific diagnostic entity.


Chapter 1 Progress in Transport and Tourism Research: Reformulating the Transport-Tourism Interface and Future Research Agendas


title: Zikavirus prME Envelope Pseudotyped Human Immunodeficiency Virus Type-1 as a Novel Tool for Glioblastoma-Directed Virotherapy

text: Glioblastoma multiforme is the most lethal type of brain tumor that is not yet curable owing to its frequent resurgence after surgery. Resistance is mainly caused by the presence of a subpopulation of tumor cells, the glioma stem cells (GSCs), which are highly resistant to radiation and chemotherapy. In 2015, Zikavirus (ZIKV)-induced microcephaly emerged in newborns, indicating that ZIKV has a specific neurotropism. Accordingly, an oncolytic tropism for infecting GSCs was demonstrated in a murine tumor model. Like other flaviviruses, ZIKV is enveloped by two proteins, prM and E. The pME expression plasmid along with the HIV-1 vector pNL Luc AM generated prME pseudotyped viral particles. Four different prME envelopes, Z1 to Z4, were cloned, and the corresponding pseudotypes, Z1- to Z4-HIVluc, produced by this two-plasmid system, were tested for entry efficiency using Vero-B4 cells. The most efficient pseudotype, Z1-HIVluc, also infected glioma-derived cell lines U87 and 86HG39. The pseudotype system was then extended by using a three-plasmid system including pME-Z1, the HIV-1 packaging plasmid psPAX2, and the lentiviral vector pLenti-luciferase-P2A-Neo. The corresponding pseudotype, designated Z1-LENTIluc, also infected U87 and 86HG39 cells. Altogether, a pseudotyped virus especially targeting glioma-derived cells might be a promising candidate for a prospective glioblastoma-directed virotherapy.


title: Recomendaciones sobre el manejo clínico de la infección por el «nuevo coronavirus» SARS-CoV2. Grupo de trabajo de la Asociación Española de Pediatría (AEP)

text: Resumen El 31 de diciembre de 2019, la Comisión Municipal de Salud y Sanidad de Wuhan (provincia de Hubei, China) informó sobre la existencia de 27 casos de neumonía de etiología desconocida con inicio de síntomas el 8 de diciembre, incluyendo 7 casos graves, con exposición común a un mercado de marisco, pescado y animales vivos en la ciudad de Wuhan. El 7 de enero de 2020, las autoridades chinas identificaron como agente causante del brote un nuevo tipo de virus de la familia Coronaviridae, denominado temporalmente «nuevo coronavirus», 2019-nCoV. El 30 de enero de 2020 la Organización Mundial de la Salud (OMS) declara el brote una Emergencia Internacional. El día 11 de febrero la OMS le asigna el nombre de SARS-CoV2 e infección COVID-19 (Coronavirus Infectious Disease). El Ministerio de Sanidad convoca a las Sociedades de Especialidades para la elaboración de un protocolo clínico de manejo de la infección. La Asociación Española de Pediatría nombra un grupo de trabajo de las Sociedades de Infectología Pediátrica y Cuidados Intensivos Pediátricos que se encargan de elaborar las presentes recomendaciones con la evidencia disponible en el momento de su realización. Abstract On 31 December 2019, the Wuhan Municipal Committee of Health and Healthcare (Hubei Province, China) reported that there were 27 cases of pneumonia of unknown origin with symptoms starting on the 8 December. There were 7 serious cases with common exposure in market with shellfish, fish, and live animals, in the city of Wuhan. On 7 January 2020, the Chinese authorities identified that the agent causing the outbreak was a new type of virus of the Coronaviridae family, temporarily called «new coronavirus», 2019-nCoV. On January 30th, 2020, the World Health Organisation (WHO) declared the outbreak an International Emergency. On 11 February 2020 the WHO assigned it the name of SARS-CoV2 and COVID-19 (SARS-CoV2 and COVID-19). The Ministry of Health summoned the Specialties Societies to prepare a clinical protocol for the management of COVID-19. The Spanish Paediatric Association appointed a Working Group of the Societies of Paediatric Infectious Diseases and Paediatric Intensive Care to prepare the present recommendations with the evidence available at the time of preparing them.


title: Infections and Their Role in Childhood Asthma Inception

text: The association of early onset wheezing with common viral and bacterial infections has raised significant interest in the role of infections in childhood asthma inception. This article serves to review these relationships among infections, host factors, and asthma inception in childhood.


Birds as sentinels for pandemic influenza


title: Nuclear/nucleolar localization properties of C-terminal nucleocapsid protein of SARS coronavirus

text: Abstract A novel coronavirus (CoV) has recently been identified as the aetiological agent of severe acute respiratory syndrome (SARS). Nucleocapsid (N) proteins of the Coronaviridae family have no discernable homology, but they share a common nucleolar-cytoplasmic distribution pattern. There are three putative nuclear localization signal (NLS) motifs present in the N. To determine the role of these putative NLSs in the intracellular localization of the SARS–CoV N, we performed a confocal microscopy analysis using rabbit anti-N antisera. In this report, we show that the wild type N was distributed mainly in the cytoplasm. The N-terminal of the N, which contains the NLS1 (aa38–44), was localized to the nucleus. The C-terminus of the N, which contains both NLS2 (aa257–265) and NLS3 (aa369–390) was localized to the cytoplasm and the nucleolus. Results derived from analysis of various deletion mutations show that the region containing amino acids 226–289 is able to mediate nucleolar localization. The deletion of two hydrophobic regions that flanked the NLS3 recovered its activity and localized to the nucleus. Furthermore, deletion of leucine rich region (220-LALLLLDRLNRL) resulted in the accumulation of N to the cytoplasm and nucleolus, and when fusing this peptide to EGFP localization was cytoplasmic, suggesting that the N may act as a shuttle protein. Differences in nuclear/nucleolar localization properties of N from other members of coronavirus family suggest a unique function for N, which may play an important role in the pathogenesis of SARS.


title: A proposal for selective resuscitation of adult cardiac arrest patients in a pandemic

text: Allocation of limited resources in pandemics begs for ethical guidance. The issue of ventilator allocation in pandemics has been reviewed by many medical ethicists, but as localities activate crisis standards of care, and health care workers are infected from patient exposure, the decision to pursue cardiopulmonary resuscitation (CPR) must also be examined to better balance the increased risks to healthcare personnel with the very low resuscitation rates of patients infected with coronavirus disease 2019 (COVID‐19) . A crisis standard of care that is equitable, transparent, and mindful of both human and physical resources will lessen the impact on society in this era of COVID‐19. This paper builds on previous work of ventilator allocation in pandemic crises to propose a literature‐based, justice‐informed ethical framework for selecting treatment options for CPR. The pandemic affects regions differently over time, so these suggested guidelines may require adaptation to local practice variations.


title: Preventing bat-born viral outbreaks in future using ecological interventions

text: [Figure: see text]


title: Molecular Epidemiology of Severe Acute Respiratory Syndrome–Associated Coronavirus Infections in Taiwan

text: Background In 2003, Taiwan experienced a series of outbreaks of severe acute respiratory syndrome (SARS) and 1 laboratory-contamination accident. Here we describe a new phylogenetic analytical method to study the sources and dissemination paths of SARS-associated coronavirus (SARS-CoV) infections in Taiwan Methods A phylogenetic analytical tool for combining nucleotide sequences from 6 variable regions of a SARS-CoV genome was developed by use of 20 published SARS-CoV sequences; and this method was validated by use of 80 published SARS-CoV sequences. Subsequently, this new tool was applied to provide a better understanding of the entire complement of Taiwanese SARS-CoV isolates, including 20 previously published and 19 identified in this study. The epidemiological data were integrated with the results from the phylogenetic tree and from the nucleotide-signature pattern Results The topologies of phylogenetic trees generated by the new and the conventional strategies were similar, with the former having better robustness than the latter, especially in comparison with the maximum-likelihood trees: the new strategy revealed that during 2003 there were 5 waves of epidemic SARS-CoV infection, which belonged to 3 phylogenetic clusters in Taiwan Conclusions The new strategy is more efficient than its conventional counterparts. The outbreaks of SARS in Taiwan originated from multiple sources


title: Analysis of thin-section CT in patients with coronavirus disease (COVID-19) after hospital discharge

text: PURPOSE: To analyze clinical and thin-section computed tomographic (CT) data from the patients with coronavirus disease (COVID-19) to predict the development of pulmonary fibrosis after hospital discharge. MATERIALS AND METHODS: Fifty-nine patients (31 males, 28 females; mean age: 41 years, range: 25 to 70 years) with confirmed COVID-19 infection performed follow-up thin-section CT of the thorax. After 31.5 days of hospital admission, the results of thin-section CT were analyzed for parenchymal abnormality (ground-glass opacification, interstitial thickening, and consolidation) and evidence of fibrosis (parenchymal band, traction bronchiectasis, and irregular interfaces). Patients were analyzed based on the evidence of fibrosis and divided into two groups, group A (with CT evidence of fibrosis) and group B (without CT evidence of fibrosis). Patient demographics, length of stay (LOS), rate of intensive care unit (ICU) admission, peak C-reactive protein level, and CT score were compared between the two groups. RESULTS: Among the 59 patients, 89.8% (53/59) patients had a typical transition from early phase to advanced phase and advanced phase to dissipating phase. Out of 59 patients, 39% (23/59) patients developed fibrosis (group A), whereas 61% (36/59) patients did not show definite fibrosis (group B). Patients in group A were older (mean age, 45.4 vs. 33.8 years), with longer LOS (19.1 vs. 15.0 days), higher rate of ICU admission (21.7% (5/23) vs. 5.6% (2/36)), higher peak C-reactive protein level (30.7 vs. 18.1 mg/L), and higher maximal CT score (5.2 vs. 4.0) than those in group B. CONCLUSIONS: Pulmonary fibrosis may develop early in patients with COVID-19 after hospital discharge. Older patients with severe illness during treatment were more prone to develop fibrosis according to thin-section CT results.


title: Influenza D virus infection in Mississippi beef cattle

text: Abstract A new member of the Orthomyxoviridae family, influenza D virus (IDV), was first reported in swine in the Midwest region of the United States. This study aims to extend our knowledge on the IDV epidemiology and to determine the impact of bovine production systems on virus spread. A total of 15 isolates were recovered from surveillance of bovine herds in Mississippi, and two genetic clades of viruses co-circulated in the same herd. Serologic assessment from neonatal beef cattle showed 94% seropositive, and presumed maternal antibody levels were substantially lower in animals over six months of age. Active IDV transmission was shown to occur at locations where young, weaned, and comingled calves were maintained. Serological characterization of archived sera suggested that IDV has been circulating in the Mississippi cattle populations since at least 2004. Continuous surveillance is needed to monitor the evolution and epidemiology of IDV in the bovine population.


Cures thermales et COVID-19


title: Activated GL7(+) B cells are maintained within the inflamed CNS in the absence of follicle formation during viral encephalomyelitis

text: Central nervous system (CNS) inflammation associated with viral infection and autoimmune disease results in the accumulation of B cells in various differentiation stages. However, the contribution between peripheral and CNS activation remains unclear. During gliatropic coronavirus induced encephalomyelitis, accumulation of protective antibody secreting cells is preceded by infiltration of B cells with a naïve and early differentiation phenotype (Phares et al., 2014). Investigation of the temporal dynamics of B cell activation in draining cervical lymph nodes (CLN) and the CNS revealed that peak CNS infiltration of early activated, unswitched IgD(+) and IgM(+) B cells coincided with polyclonal activation in CLN. By contrast, isotype-switched IgG(+) B cells did not accumulate until peripheral germinal center formation. In the CNS, unswitched B cells were confined to the perivascular space and meninges, with only rare B cell clusters, while isotype-switched B cells localized to parenchymal areas. Although ectopic follicle formation was not observed, more differentiated B cell subsets within the CNS expressed the germinal center marker GL7, albeit at lower levels than CLN counterparts. During chronic infection, CNS IgD(int) and IgD(−) B cell subsets further displayed sustained markers of proliferation and CD4 T cell help, which were only transiently expressed in the CLN. A contribution of local CD4 T cell help to sustain B cell activation was supported by occasional B cells adjacent to T cells. The results suggest that accumulation of differentiated B cell subsets within the CNS is largely dictated by peripheral activation, but that local events contribute to their sustained activation independent of ectopic follicle formation.


title: Decreased plasma levels of the survival factor renalase are associated with worse outcomes in COVID-19

text: Introduction: Renalase (RNLS), a novel secreted plasma flavoprotein, has anti-inflammatory effects in a variety of disease processes. Severe COVID-19 disease is associated with disordered inflammatory responses. We hypothesized that reduced plasma RNLS levels could be a marker of COVID-19 disease severity. Methods: Plasma was collected from 51 hospitalized COVID-19 patients and 15 uninfected non-hospitalized controls. Plasma RNLS and cytokine levels were measured and sociodemographic and clinical data were collected from chart review. Data were analyzed using nonparametric analyses and Kaplan Meir curve log rank analysis. Results: Plasma RNLs levels were negatively correlated with inflammatory markers, including IL-1b, IL-6, and TNFa (p = 0.04, p = 0.03, p = 0.01, respectively). Patients with COVID-19 disease had lower levels of RNLS than controls. Lower levels of RNLS were associated with more severe disease among COVID-19 patients. Low RNLS was also associated with worse survival among COVID-19 patients (HR = 4.54; 95% CI: 1.06-19.43; p = 0.005). Conclusion: Low plasma RNLS levels are associated with severe COVID-19 disease and may be a useful additional biomarker when identifying patients with severe COVID-19 disease. Given RNLS anti-inflammatory properties and negative correlation with inflammatory markers, these findings also suggest evidence of a potential pathophysiological mechanism for severe COVID-19 disease.


title: A career in biophysics

text: My career in science started with my PhD under Professor Darcy Gilmour at the University of Sydney. I quickly learned his iconoclastic ways and completed the degree in early 1969 in just over three years. Professor Charles Birch was the Head of Zoology and had been watching my progress and offered me a position as Lecturer as soon as my PhD was submitted. He asked me to set up a new course on invertebrate physiology, and the salary enabled me to afford the airfare to San Francisco for my family. In December 1969, I headed to the University of California San Francisco to work with Manuel Morales in the renowned Cardiovascular Research Institute headed by Julius Comroe (1965), the author of the textbook of pulmonary physiology, The Lung. I had a great time there meeting many important scientists that I had only read about, including Setsuro Ebashi, Andrew Huxley, Fumio Oosawa and Bernard Katz who had just won his Nobel Prize. It was inspiring. For the next two and a half years, I immersed myself in fluorescence polarisation spectroscopy, and rubbed up against with some of the best minds in the muscle field including Roger Cooke. Manuel Morales sent Roger to collect this Aussie and his family, and we have remained friends ever since.


title: FDG-PET/CT findings highly suspicious for COVID-19 in an Italian case series of asymptomatic patients

text: AIM: To illustrate the [18F]FDG-PET/CT findings in patients affected by cancer with clinical diagnosis of Covid-19 METHODS: We retrospectively reviewed the cases of patients who showed pulmonary involvement unrelated to cancer metastases on March 13 and 16 2020. We reviewed the scans, collected medical history, and exposure information. RESULTS: Among the 13 scans, we identified 5 cases with imaging findings suspicious for viral infection. Peripheral lung consolidations and/or ground-glass opacities in two or more lobes were found. Lung abnormalities displayed increased [18F]FDG uptake (SUVmax 4.3–11.3). All the patients on the day of PET/CT acquisition were asymptomatic, and they did not have fever or cough. In view of the PET/CT findings, home isolation, symptom surveillance, and treatment (in 3/5 patients) were indicated. At 1-week follow-up, 2/5 patients experienced the onset of mild respiratory symptoms. CONCLUSIONS: The [18F]FDG-PET/CT can identify probable Covid-19 disease in the absence or before symptoms onset and can guide patient management. Nuclear medicine staff needs to be aware of the possibility of contact with patients affected by the SARS-CoV-2 infection even if they do not present any symptom. Therefore, safety measures need to be adopted for other patients and hospital staff in order to block the spread of infection.


title: Bovine Neonatal Immunology

text: Early fetal immune development occurs independent of antigen exposure, whereas later development depends on exposure to specific antigens. Although neonates are immunocompetent at birth, they are clearly immunonaive and dependent on passively acquired maternal immunoglobulins, immune cells, and other substances from colostrum for protection. Neonates that suffer failure of passive transfer of maternal immunoglobulins may be at increased risk for disease; however, many other factors interact in conjunction with the level of passively acquired immunoglobulin to determine the occurrence of disease.


title: Global commercial passenger airlines and travel health information regarding infection control and the prevention of infectious disease: What's in a website?

text: Abstract Background Air travel has never been easier, cheaper or faster, with large volumes of people travelling around the world. These factors increase the risk of the spread of infectious diseases by air travel. Little is known, however, about the extent to which airlines provide information to passengers on infection control and measures to prevent the spread of infectious diseases. This study examined the websites of the global commercial passenger airlines to see if they contained information about infection control and prevention of infectious diseases and appraised the clinical usefulness of that information. Method A cross-sectional text-based analysis of the 73 airline websites from the six global commercial passenger airline conglomerates was performed to identify information about infection control and prevention of infectious between July and August 2019. Results Of the 73 airline websites, less than half (n = 35, 28.6%) contained information deemed useful for passengers. While there was a range of general health advice within the websites, there was limited information about infection control and preventing infectious diseases. A minority of websites contained information about vaccination status prior to travel, and to a lesser extent handwashing and hand hygiene, with very few including disease-specific advice or preventive measures. Conclusions Airline websites are an underutilised source of information for infection control and the prevention of infectious diseases. Providing passengers with information on basic infection control and prevention measures may support the global efforts against the spread of infectious diseases.


title: Effects of chloroquine on viral infections: an old drug against today's diseases

text: Summary Chloroquine is a 9-aminoquinoline known since 1934. Apart from its well-known antimalarial effects, the drug has interesting biochemical properties that might be applied against some viral infections. Chloroquine exerts direct antiviral effects, inhibiting pH-dependent steps of the replication of several viruses including members of the flaviviruses, retroviruses, and coronaviruses. Its best-studied effects are those against HIV replication, which are being tested in clinical trials. Moreover, chloroquine has immunomodulatory effects, suppressing the production/release of tumour necrosis factor α and interleukin 6, which mediate the inflammatory complications of several viral diseases. We review the available information on the effects of chloroquine on viral infections, raising the question of whether this old drug may experience a revival in the clinical management of viral diseases such as AIDS and severe acute respiratory syndrome, which afflict mankind in the era of globalisation.


title: Duration of challenge immunity to coronavirus JHM in mice

text: The duration of challenge resistance in mice immunized with mouse hepatitis virus (MHV) strain JHM was examined as a model of immunity to corona-virus infection. Genetically susceptible BALB/cByJ mice were immunized by intranasal (i.n.) or per os (p.o.) inoculation with MHV-JHM or sterile tissue culture fluid (sham) then challenged i.n. with MHV-JHM or sterile tissue culture fluid 1, 6, or 12 months later. Four days after challenge, virus in nasal turbinates and liver was quantified, and prevalance of microscopic lesions in liver and gut-associated lymphoid tissue was tabulated as indices of challenge resistance. MHV-immunized and challenged groups were compared to sham-immunized and challenged groups. Mice immunized by i.n. inoculation were strongly resistant to challenge at 1, 6, and 12 months. Mice immunized by p.o. inoculation were resistant at 1 month, but became partially susceptible to reinfection at 6 and 12 months, based upon all indices. These data indicate that, depending upon route of immunization, mice can become susceptible to reinfection with the same coronavirus strain over time.


title: Effects of cold storage on detection of avian infectious bronchitis virus in chicken carcasses and local antibodies in tracheal washes

text: Abstract In order to test the survivability of infectious bronchitis virus (IBV) in dead chicken carcasses during 24h of cold storage, 7 week-old specific-pathogen-free chickens were infected with virulent IBV Massachusetts strain M41, and were killed humanely 10 days later. Carcasses were stored in a cold room at 4°C. After 1, 3, 6, 9, 12 or 24h of storage, necropsies were carried out. Trachea, lung, kidney and rectum were collected for virus isolation by tracheal organ culture (TOC) or embryonated chicken eggs (ECE), and detection by nested reverse-transcriptase polymerase chain reaction (RT-PCR). IBV was detected by RT-PCR at all sampling times, except for 1 and 6h of storage in kidney and 9h of storage in kidney and rectum. For ECE, isolation was obtained at all sampling points, except at 1 and 24h of storage in lungs. Isolation by tracheal organ cultures was less successful, except from rectum. In addition to sampling for virus, tracheal washes were collected from each carcass to measure the ability to detect local antibodies after storage. Levels of IgA in tracheal washes remained high for up to 9h of storage, suggesting that accurate sampling for research purposes when required must be carried out within this time.


title: Structure–function analysis and molecular modeling of DNase catalytic antibodies

text: Abstract There is great interest in the antibodies-to-DNA transformation, since this change is characteristic of autoimmune diseases and contributes to its pathology. After immunization and fusions, 14 hybridomas bearing DNA-hydrolysis activity against pUC19 plasmid DNA were obtained. Genes coding for VH and VL regions of the 14 monoclonal antibodies (mAbs) were cloned and sequenced. The sequences were compared with sequences of the Ig-Blast database to determine their germline and to identify potential mutations responsible for DNA binding and DNase activity. V genes of the H chains’ genes expressed four genes of the VH1/J558 family, three of VH5/VH7183, and three of VH8/VH3609. The genetic repertoire of these mAbs was examined by determining the nucleotide sequences of their H chain V regions. This VH and VL domain was most similar to an anti-ssDNA (DNA-1) antibody as well as to catalytic autoimmune mAb (m3D8). Computer-generated models of the three-dimensional structures of VH and VL (VHL4) of the IgG4 combinations were used to define the positions occupied by the important sequence motifs at the binding sites. The modeling structure showed that VHL4 binds to oligo (dT3) primarily by sandwiching thymine bases between Tyr L32, Tyr L49 and Tyr H97 side-chains. Superposing VHL4 with anti-nucleic acid m3D8 catAbs revealed a common ssDNA recognition module consisting of His L93, His H35 residues which are critical for DNA-hydrolyzing antibodies. This study demonstrates the potential usefulness of the protein DNA surrogate in the investigation of the origin of anti-DNA antibodies’ hydrolyzing activities.


title: Prevalence of Pulmonary Infections Caused by Atypical Pathogens in non-HIV Immunocompromised Patients

text: Although atypical bacteria are important causes of lower airway infections, data on their role in immunocompromised patients are scarce. The aim of the study was to evaluate the prevalence of atypical pulmonary infections in patients with various types of immunosuppression, and to analyze clinical characteristics of these infections. Eighty non-HIV immunocompromised patients with different underlying diseases and clinical and radiological signs of pulmonary infection were enrolled. Due to incomplete data on eight patients, 72 patients were eligible for final analysis (median age 58 years). All patients underwent fiberoptic bronchoscopy and bronchoalveolar lavage. Bronchoalveolar lavage fluid (BALF) fluid samples were sent for direct microscopy, cultures, and fungal antigen detection, when appropriate. Commercial qualitative amplification assay (PNEUMOTRIS oligomix Alert Kit(®)), based on nested PCR method, was used to detect specific DNA sequences of L. pneumophila, C. pneumoniae, and M. pneumoniae in BALF. There were 61 (84.7 %) patients with hematologic diseases, 3 (4.2 %) after solid organ transplantation, and 8 (11.1 %) with miscellaneous diseases affecting immune status. Specific sequences of M. pneumoniae, C. pneumoniae, and L. pneumophila DNA were found in 7 (9.7 %), 2 (2.8 %), and 0 patients, respectively. In 8 of these patients co-infections with different microorganisms were demonstrated. Co-infection with A. baumanii and P. aeruginosa was diagnosed in three patients who died. We conclude that atypical lower airway infections are uncommon in immunocompromised patients. The majority of these infections are co-infections rather than single pathogen infections.


A proposal for appropriate countermeasures to infectious diseases in schools


title: Prevalence of rhinoviruses in young children of an unselected birth cohort from the Netherlands

text: Abstract Rhinovirus (RV) is a frequent pathogen in young children, eliciting symptoms ranging from common colds to wheezing illnesses and lower respiratory tract infections. The recently identified RV-C seems to be associated with asthma exacerbations and more severe disease, but results vary. We studied the prevalence and severity of infection with RV in an unselected birth cohort. Children with respiratory symptoms entered the symptomatic arm of the cohort and were compared with asymptomatic children. Severity of wheezing and other respiratory symptoms was registered. Respiratory viruses were evaluated using throat and nasopharyngeal swabs on first presentation and after recovery (wheezing children). RV genotyping was performed on RV-PCR positive samples. RV was the most prevalent respiratory virus and was found in 58/140 symptomatic children (41%), 24/96 (25%) control children and 19/74 (26%) wheezing symptomatic children after recovery (p <0.05) and did not differ between wheezing and non-wheezing symptomatic children—respectively, 42% (38/90) and 40% (20/50). RV-A was the most commonly detected species (40/68, 59%), followed by RV-C (22/68, 32%) and RV-B (6/68, 9%). RV-B was more frequently detected in asymptomatic children (5/6, p <0.05). There was no significant difference in the frequency of RV species between wheezing and non-wheezing symptomatic children. Children with RV mono-infection had more severe symptoms, but no association between RV species and severity of disease was seen. In an unselected birth cohort from the Netherlands with mild respiratory disease RV was the most prevalent respiratory virus. RV(-C) infection was not associated with more severe disease or wheezing.


title: STING: infection, inflammation and cancer

text: The rapid detection of microbial agents is essential for the effective initiation of host defence mechanisms against infection. Understanding how cells detect cytosolic DNA to trigger innate immune gene transcription has important implications — not only for comprehending the immune response to pathogens but also for elucidating the causes of autoinflammatory disease involving the sensing of self-DNA and the generation of effective antitumour adaptive immunity. The discovery of the STING (stimulator of interferon genes)-controlled innate immune pathway, which mediates cytosolic DNA-induced signalling events, has recently provided important insights into these processes, opening the way for the development of novel immunization regimes, as well as therapies to treat autoinflammatory disease and cancer.


title: Regulation and function of CMTR1‐dependent mRNA cap methylation

text: mRNA is modified co‐transcriptionally at the 5′ end by the addition of an inverted guanosine cap structure which can be methylated at several positions. The mRNA cap recruits proteins involved in gene expression and identifies the transcript as being cellular or ‘self’ in the innate immune response. Methylation of the first transcribed nucleotide on the ribose 2′‐O position is a prevalent cap modification which has roles in splicing, translation and provides protection against the innate immune response. In this review, we discuss the regulation and function of CMTR1, the first transcribed nucleotide ribose 2′‐O methyltransferase, and the molecular interactions which mediate methylated 2′‐O ribose function. WIREs RNA 2017, 8:e1450. doi: 10.1002/wrna.1450 1.. RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications; 2.. RNA Processing > Capping and 5' End Modifications; 3.. RNA in Disease and Development > RNA in Disease.


title: Could a mannequin simplify rhinopharyngeal swab collection in COVID 19 patients?

text: Rhinopharyngeal swab collection is used to test patients for COVID-19; unfortunately, the false negative rate is around 30% in symptomatic patients, and maybe even higher in asymptomatic ones. A correct swab collection is consequently critical. Swabs are usually performed by dedicated personnel, but at the present moment, the methods for its training are not standardized. In a Letter to the Editor recently published in the European Archives of Otorhinolaringology, Tagliabue et al. describe the training method used in their Institution: the personnel dedicated to swab collection increases its confidence with the procedure by observing endoscopic anatomy, while an otolaryngologist performs rigid endoscopy. Although we found this paper interesting, we think that the author’s proposal has timing and financial drawbacks that should be considered in daily activity, especially in an emergency period like the pandemic we are experiencing. In this Letter to the Editor, we discuss some pre-analytic and analytic issues that should be considered while performing rhinopharyngeal swabs, and we propose the use of a mannequin to train personnel, thus reducing the risk of infection for health workers, and patient’s discomfort.


title: Chemical composition, antimicrobial activity against Staphylococcus aureus and a pro-apoptotic effect in SGC-7901 of the essential oil from Toona sinensis (A. Juss.) Roem. leaves

text: Abstract Ethnopharmacological relevance Leaves of Toona sinensis (A. Juss.) Roem. (TSL), a popular vegetable in China, have anti-inflammatory, antidoting, and worm-killing effects and are used in folk medicine for the treatment of enteritis, dysentery, carbuncles, boils, and especially abdominal tumors. Our aim was to investigate the in vitro antimicrobial activity against Staphylococcus aureus and anticancer property of the essential oil from TSL (TSL-EO), especially the pro-apoptotic effect in SGC-7901. Materials and methods TSL-EO obtained by hydrodistillation was analyzed by GC/MS and was tested in vitro against twenty clinically isolated strains of Staphylococcus aureus (SA 1–20), which were either methicillin-sensitive Staphylococcus aureus (MSSA) or methicillin-resistant Staphylococcus aureus (MRSA) and two standard strains viz. ATCC 25923 and ATCC 43300. The anticancer activity of TSL-EO was evaluated in vitro against HepG2, SGC7901, and HT29 through MTT assay. Moreover, the apoptosis-inducing activity of TSL-EO in SGC7901 cells was determined by Hoechst 33324 staining and flow cytometry methods. Also, the apoptosis-related proteins viz. Bax, Bcl-2 and caspase-3 were detected by western-blotting. Results GC–MS analysis showed that TSL-EO contained a high amount of sesquiterpenes (84.64%), including copaene (8.27%), β-caryophyllene (10.16%), caryophyllene (13.18%) and β-eudesmene (5.06%). TSL-EO inhibited the growth of both MSSA and MRSA, with the lowest MIC values of 0.125 and 1mg/ml, respectively. Treatment with TSL-EO for 24h could significantly suppress the viability of three different cancer cell lines (P<0.05). Furthermore, the apoptosis-inducing activity of TSL-EO in SGC7901 cells increased in a dose-dependent manner, potentially resulting from the up-regulated expression of Bax, caspase-3 and down-regulated expression of Bcl-2. Conclusions TSL-EO possessed antibacterial activity against Staphylococcus aureus and significant cytotoxicity against cancer cells and particularly prominent pro-apoptotic activity in SGC7901 cells. These bioactivities were probably due to the high content of sesquiterpenes. Our results suggested that TSL-EO possessed potential health benefits and could serve as a promising natural food addictive.


title: Respiratory syncytial virus entry and how to block it

text: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease in young children and elderly people. Although the virus was isolated in 1955, an effective RSV vaccine has not been developed, and the only licensed intervention is passive immunoprophylaxis of high-risk infants with a humanized monoclonal antibody. During the past 5 years, however, there has been substantial progress in our understanding of the structure and function of the RSV glycoproteins and their interactions with host cell factors that mediate entry. This period has coincided with renewed interest in developing effective interventions, including the isolation of potent monoclonal antibodies and small molecules and the design of novel vaccine candidates. In this Review, we summarize the recent findings that have begun to elucidate RSV entry mechanisms, describe progress on the development of new interventions and conclude with a perspective on gaps in our knowledge that require further investigation.


title: Associating Changes in the Immune System with Clinical Diseases for Interpretation in Risk Assessment

text: This overview unit discusses the relationship between immunosuppression, a potential consequence of immunotoxicity, and disease progression. It also discusses other factors, such as stress and age, that affect disease susceptibility. These factors play an important role in risk assessment for exposures to environmental factors.


title: Is diabetes mellitus associated with mortality and severity of COVID-19? A meta-analysis

text: Abstract Background Many studies on COVID-19 have reported diabetes to be associated with severe disease and mortality, however, the data is conflicting. The objectives of this meta-analysis were to explore the relationship between diabetes and COVID-19 mortality and severity, and to determine the prevalence of diabetes in patients with COVID-19. Methods We searched the PubMed for case-control studies in English, published between Jan 1 and Apr 22, 2020, that had data on diabetes in patients with COVID-19. The frequency of diabetes was compared between patients with and without the composite endpoint of mortality or severity. Random effects model was used with odds ratio as the effect size. We also determined the pooled prevalence of diabetes in patients with COVID-19. Heterogeneity and publication bias were taken care by meta-regression, sub-group analyses, and trim and fill methods. Results We included 33 studies (16,003 patients) and found diabetes to be significantly associated with mortality of COVID-19 with a pooled odds ratio of 1.90 (95% CI: 1.37–2.64; p < 0.01). Diabetes was also associated with severe COVID-19 with a pooled odds ratio of 2.75 (95% CI: 2.09–3.62; p < 0.01). The combined corrected pooled odds ratio of mortality or severity was 2.16 (95% CI: 1.74–2.68; p < 0.01). The pooled prevalence of diabetes in patients with COVID-19 was 9.8% (95% CI: 8.7%–10.9%) (after adjusting for heterogeneity). Conclusions Diabetes in patients with COVID-19 is associated with a two-fold increase in mortality as well as severity of COVID-19, as compared to non-diabetics. Further studies on the pathogenic mechanisms and therapeutic implications need to be done.


title: The COVID19 pandemic crisis and the relevance of a farm-system-for-nutrition approach

text: The Covid19 pandemic should be seen as a wake-up call for humanity, to reflect, rethink and redesign food systems that are safe, healthy, sustainable, and beneficial to all. This crisis has disrupted food supply chains, affecting lives and livelihoods. Hunger and malnutrition is expected to increase and the poor and vulnerable will suffer the most. There is urgent need to build resilient food systems. A location specific farm-system-for-nutrition approach, based on sustainable use of natural resources and local agri-food value chains can help improve household diet diversity and address nutrition deficiencies. The food-based approach can improve preparedness and resilience of communities to withstand the challenge posed by crises in general, and COVID19 in particular.


title: Overlapping findings or oral manifestations in new SARS‐CoV‐2 infection?

text: We have read the short communication “Oral vesiculobullous lesions associated with SARS‐CoV‐2 infection” (Martin Carreras‐Presas, Amaro Sanchez, Lopez‐Sanchez, Jane‐Salas, & Somacarrera Perez, 2020) by Dr. Martín Carreras‐Presas et al. with great interest. We congratulate the team for contributing to the knowledge about this devastating infection in such challenging times. However, we raise some concerns that must be addressed.


title: Effect of Glucocorticoid on Piglet Jejunal Mucosa during Acute Viral Enteritis

text: ABSTRACT: We measured the effect of pharmacological doses of glucocorticoid on piglet jejunal structure and function during acute viral diarrhea. Weaned piglets, infected experimentally with transmissible gastroenteritis virus, a coronavirus that induces a diarrheal illness similar to human rotavirus infection, received methylprednisolone (30 mg/kg) or saline intramuscularly at 48 and 72 h after infection; noninfected littermate controls were similarly injected with methylprednisolone. Animals were killed at 96 h, at the height of diarrhea, and jejunal epithelium was studied in vitro. Transmissible gastroenteritis, as expected, induced structural, enzyme, and Na transport abnormalities. Methylprednisolone did not affect small intestinal structure or function of noninfected control piglets. In transmissible gastroenteritis-infected piglets, jejunal villi were longer and glucose-facilitated Na absorption was greater after methylprednisolone than after saline treatment. Increased glucose stimulation of Na flux in vitro in the methylprednisolone-treated infected group was not attributable to enhanced Na(+)-K(+)-ATPase activity and occurred despite persistence of the virus within mucosal cells, shown by immunofluorescense microscopy. In this piglet model of viral diarrhea, early regeneration of absorptive surface that precedes recovery of disaccharidase function is accelerated by glucocorticoid therapy.


title: Protective effect of an inactivated avian coronavirus vaccine administered by aerosol

text: The antigenicity and protective effect of 3 strains of avian infectious bronchitis virus inactivated by beta-propiolactone were studied. Chickens administered 2 doses of the inactivated Connecticut strain (IBV-46) vaccine by aerosol at 3-week intervals had significant levels of virus-neutralizing antibodies and were resistant to infection by the Massachusetts strain (IBV-41) as determined by virus isolation attempts. Antibody levels in chickens given inactivated Iowa 33 and Iowa 609 were not significant and they were not resistant to infection by IBV-41.


title: Synthesis revolution

text: Evidence synthesis facilitates a more robust understanding of generalities in ecology and evolution, as well as the effectiveness of conservation interventions. However, as synthesis methods become embedded in research workflows, it is imperative that the next generation of researchers receives sufficient training.


title: Global health concerns stirred by emerging viral infections

text: Emerging viral infections continue to pose a major threat to global public health. In 1997, a highly pathogenic avian influenza A (H5N1) virus was found to directly spread from poultry to humans unlike previously reported transmission routs of human-to-human and livestock-to-human, stirring a grave concern for a possible influenza pandemic. This article is protected by copyright. All rights reserved.


title: Presumed Caudal Cerebellar Artery Infarction in Three Cats: Neurological Signs, MRI Findings, and Outcome

text: Ischemic cerebrovascular disease (CVD) is a relatively common condition in dogs but infrequent in cats, with acute or peracute onset of non-progressive neurological signs. Cerebellar artery infarction appears to be very uncommon in cats, with only two cases reported affecting the rostral cerebellar artery (RCA). This study aims to report for the first time the neurological signs, magnetic resonance imaging (MRI) findings and outcome in three cats diagnosed with presumed caudal cerebellar artery (CCA) infarction. Unique presentation of vestibular signs associated with CCA in three cats and similarities between dogs and humans are discussed.


title: Effective inactivation of a wide range of viruses by pasteurization

text: BACKGROUND: Careful selection and testing of plasma reduces the risk of blood‐borne viruses in the starting material for plasma‐derived products. Furthermore, effective measures such as pasteurization at 60°C for 10 hours have been implemented in the manufacturing process of therapeutic plasma proteins such as human albumin, coagulation factors, immunoglobulins, and enzyme inhibitors to inactivate blood‐borne viruses of concern. A comprehensive compilation of the virus reduction capacity of pasteurization is presented including the effect of stabilizers used to protect the therapeutic protein from modifications during heat treatment. STUDY DESIGN AND METHODS: The virus inactivation kinetics of pasteurization for a broad range of viruses were evaluated in the relevant intermediates from more than 15 different plasma manufacturing processes. Studies were carried out under the routine manufacturing target variables, such as temperature and product‐specific stabilizer composition. Additional studies were also performed under robustness conditions, that is, outside production specifications. RESULTS: The data demonstrate that pasteurization inactivates a wide range of enveloped and nonenveloped viruses of diverse physicochemical characteristics. After a maximum of 6 hours' incubation, no residual infectivity could be detected for the majority of enveloped viruses. Effective inactivation of a range of nonenveloped viruses, with the exception of nonhuman parvoviruses, was documented. CONCLUSION: Pasteurization is a very robust and reliable virus inactivation method with a broad effectiveness against known blood‐borne pathogens and emerging or potentially emerging viruses. Pasteurization has proven itself to be a highly effective step, in combination with other complementary safety measures, toward assuring the virus safety of final product.


title: Prise en charge des infections des voies respiratoires basses de l'immunocompétent. Partie concernant les définitions, l'épidémiologie et les éléments du diagnostic

text: Résumé Les infections respiratoires basses sont une des principales cause de mortalité dans le monde et les pneumopathies représentent en France la première cause de décès d'origine infectieuse. Trois entités nosologiques distinctes sont habituellement isolées en fonction de la localisation infectieuse : la bronchite aiguë, la pneumopathie et la bronchopneumopathie (atteignant les bronches et le parenchyme pulmonaire). En cas d'infections de l'arbre bronchique dans le cadre d'une bronchopathie chronique on parle de décompensation infectieuse de la maladie bronchique. Les deux principales difficultés diagnostiques de ces infections sont de déterminer la présence d'une participation alvéolaire au processus infectieux et de définir l'agent (ou les agents) pathogènes. Ces deux éléments vont conditionner la prise en charge thérapeutique. En dehors de l'examen physique, indispensable dans ce contexte, seule la radiographie thoracique pourra, en cas de persistance d'un doute, permettre de confirmer la présence d'une participation alvéolaire. Le diagnostic microbiologique pose la question de sa nécessité systématique et celui de sa valeur. Il n'est pas indispensable de réaliser un diagnostic microbiologique de certitude dans tous les cas. La décision de documentation doit répondre à deux impératifs : faisabilité et valeur diagnostique. La valeur d'un prélèvement dépend de son aptitude à mettre en évidence l'agent pathogène et dans certains cas de la possibilité d'en déterminer le profil de sensibilité (qui reste une indication majeure à la réalisation de ces prélèvements). Abstract Particular attention is given to lower respiratory tract infections because of their frequency and potential severity. These infections represent a major cause of death worldwide and pneumonia remains the first cause of death from infectious origin in France. Three nosological entities are usually described according to the anatomic localization of the infectious process: acute bronchitis, pneumonia, and bronchopneumonia (if the infection involves the bronchial tree and the lung parenchyma). If bronchial infection occurs within the context of a chronic respiratory tract disease, it is called acute decompensation of chronic lung disease (usually chronic obstructive pulmonary disease). The major diagnostic difficulties are to be able to confirm alveolar implication in the infectious process and to determine the pathogenic agent(s) responsible for the clinical pattern. This information is essential for subsequent care depends. Apart from clinical examination, essential in this context, only chest-X-rays can be of any help to confirm alveolar involvement in the disease process. On the contrary, the interest of systematic microbiological confirmation and its value according to various techniques and swab conditions may be questioned for the clinical diagnosis. Microbiological confirmation does not seem essential in every case. The feasibility and relevance of microbiological techniques must be determined before any decision is taken on documentation. The microbiological documentation value depends on its yield and sensitivity profile in identifying the pathogen.


title: A rapid and quantitative assay for measuring neutralizing antibodies of Coxsackievirus B3

text: Abstract Coxsackievirus B3 (CVB3) infection has been found to account for an increasing proportion cases of hand, foot and mouth disease (HFMD) in recent epidemiology studies. CVB3 is a single stranded, non-enveloped RNA virus and the infection can cause prominent health threat to pre-school children. Here, by taking approaches of reverse genetics, we established a single-round infection system for CVB3. The pseudovirus was produced by sequential transfection of CVB3 capsid expresser plasmid and CVB3 replicon RNA bearing firefly luciferase as a reporter. The CVB3 pseudovirus system was used for quantifying neutralizing antibody (NtAb) levels of 720 human serum samples and showed superior specificity and sensitivity comparing traditional cytopathic effect (CPE) assay. Furthermore, we compared the seroprevalence of CVB3 NtAbs in pre-school children and healthy adults, and found that only 11.94% of pre-school children were NtAbs positive which suggested that most children were naive to CVB3 infection; while there is much higher positive rate in adults (60%) indicating that most adults have experienced CVB3 infection during childhood. This rapid and quantitative assay greatly facilitates evaluating the level of NtAbs against CVB3 in populations and will help to advance CVB3 vaccine development.


title: Mobility

text: Mobility and movement are of concern to academics working across the social sciences, and this article provides a critical evaluation of current geographical research on mobility. Mobilities are fundamental to our daily lives and to the functioning of societies and economies, and the article begins by examining how geographers have approached mobility and fixity during the past half century and why there appears to have been a resurgence of research on mobility in the past decade. Mobilities are entwined with complex power relationships and the article examines how governments and businesses have attempted to encourage and facilitate the movements of people and things, while controlling and regulating mobilities which are deemed to be threatening, out of place, and uncontrolled – such as the mobility of gypsies and illegal immigrants. The article examines how mobilities have frequently been pushed into the background in accounts of landscape and place, before showing how geographers have more recently begun to take account of movement, change, and dynamism in conceptualizing place and landscape. The final section examines how human geographers and social scientists have been paying increasing attention to the social and cultural dimensions of travel and transport, and focuses on recent work on the geographies of the car and driving.


title: Generation and protective efficacy of a cold-adapted attenuated genotype 2b porcine epidemic diarrhea virus

text: The recent emergence and re-emergence of porcine epidemic diarrhea virus (PEDV) underscore the urgent need for the development of novel, safe, and effective vaccines against the prevailing strain. In this study, we generated a cold-adapted live attenuated vaccine candidate (Aram-P29-CA) by short-term passage of a virulent PEDV isolate at successively lower temperatures in Vero cells. Whole genome sequencing identified 12 amino acid changes in the cold-adapted strain with no insertions and deletions throughout the genome. Animal inoculation experiments confirmed the attenuated phenotype of Aram-P29-CA virus in the natural host. Pregnant sows were orally administered P29-CA live vaccines two doses at 2-week intervals prior to parturition, and the newborn piglets were challenged with the parental virus. The oral homologous prime-boost vaccination of P29-CA significantly improved the survival rate of the piglets and notably mitigated the severity of diarrhea and PEDV fecal shedding after the challenge. Furthermore, strong antibody responses to PEDV were detected in the sera and colostrum of immunized sows and in the sera of their offspring. These results demonstrated that the cold-adapted attenuated virus can be used as a live vaccine in maternal vaccination strategies to provide durable lactogenic immunity and confer passive protection to litters against PEDV.


MANIFESTACIONES CUTÁNEAS EN CONTEXTO DEL BROTE ACTUAL DE ENFERMEDAD POR CORONAVIRUS 2019


title: Pneumothorax, Bullous Disease, and Emphysema

text: This article addresses several distinct but related pulmonary conditions that are commonly referred to general thoracic surgeons for decision making and management. The management of various types of pneumothorax is reviewed, with particular attention to the selection of the appropriate level of surgical intervention. The related entities of bullous lung disease and diffuse emphysema are discussed, with a focus on the identification of appropriate circumstances for surgical intervention. The summarized work and the treatment recommendations are supported with an extensive bibliography of important work in this area.


title: Novel genetically-modified chimpanzee adenovirus and MVA-vectored respiratory syncytial virus vaccine safely boosts humoral and cellular immunity in healthy older adults

text: Abstract Objectives Respiratory syncytial virus (RSV) causes respiratory infection across the world, with infants and the elderly at particular risk of developing severe disease and death. The replication-defective chimpanzee adenovirus (PanAd3-RSV) and modified vaccinia virus Ankara (MVA-RSV) vaccines were shown to be safe and immunogenic in young healthy adults. Here we report an extension to this first-in-man vaccine trial to include healthy older adults aged 60–75 years. Methods We evaluated the safety and immunogenicity of a single dose of MVA-RSV given by intra-muscular (IM) injection (n = 6), two doses of IM PanAd3-RSV given 4-weeks apart (n = 6), IM PanAd3-RSV prime and IM MVA-RSV boost 8-weeks later (n = 6), intra-nasal (IN) spray of PanAd3-RSV prime and IM MVA-RSV boost 8-weeks later (n = 6), or no vaccine (n = 6). Safety measures included all adverse events within one week of vaccination and blood monitoring. Immunogenicity measures included serum antibody responses (RSV- and PanAd3-neutralising antibody titres measured by plaque-reduction neutralisation and SEAP assays, respectively), peripheral B-cell immune responses (frequencies of F-specific IgG and IgA antibody secreting cells and memory B-cells by ex vivo and cultured dual-colour ELISpot assays respectively), and peripheral RSV-specific T-cell immune responses (frequencies of IFNγ-producing T-cells by ex vivo ELISpot and CD4+/CD8+/Tfh-like cell frequencies by ICS/FACS assay). Results The vaccines were safe and well tolerated. Compared with each individual baseline immunity the mean fold-changes in serum RSV-neutralising antibody, appearance and magnitude of F-specific IgG and IgA ASCs and expansion of CD4+/CD8+ IFNγ-producing T-cells in peripheral circulation were comparable to the results seen from younger healthy adults who received the same vaccine combination and dose. There were little/no IgA memory B-cell responses in younger and older adults. Expansion of IFNγ-producing T-cells was most marked in older adults following IM prime, with balanced CD4+ and CD8+ T cell responses. The RSV-specific immune responses to vaccination did not appear to be attenuated in the presence of PanAd3 (vector) neutralising antibody. Conclusions PanAd3-RSV and MVA-RSV was safe and immunogenic in older adults and the parallel induction of RSV-specific humoral and cellular immunity merits further assessment in providing protection from severe disease.


title: Emerging zoonotic viral infections of occupational health importance

text: Emerging viral infections represent a public health risk pointed out by the spreading of pathogens with potential zoonotic risk. Moreover, the risk of zoonosis has probably been underestimated in occupational settings. A literature review between 2007 and 2018 was performed to identify evidences concerning the epidemiological associations between some emerging viruses and occupational diseases. Observational studies and case-reports were selected and analyzed. West Nile Virus (WNV) disease, Crimean-Congo Hemorrhagic Fever (CCHF) disease and Hepatitis E virus (HEV) infection were included in the review for their potential zoonotic transmission. The most important risk factor for acquiring WNV infection and CCHF infection is the exposure to infected mosquitoes and ticks, respectively; therefore, outdoor workers are at risk of infection. HEV is responsible for epidemics and endemics of acute hepatitis in humans, that can become infected through waterborne, foodborne and zoonotic transmission routes. A total of 10, 34 and 45 eligible studies for WNV, CCHF virus (CCFHV) and HEV, respectively, were analyzed by year, country, study design, risk group and outcomes. The occupational risk groups mainly included farm and agricultural workers, veterinarians, slaughterers, animal handlers, healthcare workers and soldiers. These findings support the need to develop effective interventions to prevent transmission of emerging viruses.


title: Transmission characteristics of MERS and SARS in the healthcare setting: a comparative study

text: BACKGROUND: The Middle East respiratory syndrome (MERS) coronavirus has caused recurrent outbreaks in the Arabian Peninsula since 2012. Although MERS has low overall human-to-human transmission potential, there is occasional amplification in the healthcare setting, a pattern reminiscent of the dynamics of the severe acute respiratory syndrome (SARS) outbreaks in 2003. Here we provide a head-to-head comparison of exposure patterns and transmission dynamics of large hospital clusters of MERS and SARS, including the most recent South Korean outbreak of MERS in 2015. METHODS: To assess the unexpected nature of the recent South Korean nosocomial outbreak of MERS and estimate the probability of future large hospital clusters, we compared exposure and transmission patterns for previously reported hospital clusters of MERS and SARS, based on individual-level data and transmission tree information. We carried out simulations of nosocomial outbreaks of MERS and SARS using branching process models rooted in transmission tree data, and inferred the probability and characteristics of large outbreaks. RESULTS: A significant fraction of MERS cases were linked to the healthcare setting, ranging from 43.5 % for the nosocomial outbreak in Jeddah, Saudi Arabia, in 2014 to 100 % for both the outbreak in Al-Hasa, Saudi Arabia, in 2013 and the outbreak in South Korea in 2015. Both MERS and SARS nosocomial outbreaks are characterized by early nosocomial super-spreading events, with the reproduction number dropping below 1 within three to five disease generations. There was a systematic difference in the exposure patterns of MERS and SARS: a majority of MERS cases occurred among patients who sought care in the same facilities as the index case, whereas there was a greater concentration of SARS cases among healthcare workers throughout the outbreak. Exposure patterns differed slightly by disease generation, however, especially for SARS. Moreover, the distributions of secondary cases per single primary case varied highly across individual hospital outbreaks (Kruskal–Wallis test; P < 0.0001), with significantly higher transmission heterogeneity in the distribution of secondary cases for MERS than SARS. Simulations indicate a 2-fold higher probability of occurrence of large outbreaks (>100 cases) for SARS than MERS (2 % versus 1 %); however, owing to higher transmission heterogeneity, the largest outbreaks of MERS are characterized by sharper incidence peaks. The probability of occurrence of MERS outbreaks larger than the South Korean cluster (n = 186) is of the order of 1 %. CONCLUSIONS: Our study suggests that the South Korean outbreak followed a similar progression to previously described hospital clusters involving coronaviruses, with early super-spreading events generating a disproportionately large number of secondary infections, and the transmission potential diminishing greatly in subsequent generations. Differences in relative exposure patterns and transmission heterogeneity of MERS and SARS could point to changes in hospital practices since 2003 or differences in transmission mechanisms of these coronaviruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-015-0450-0) contains supplementary material, which is available to authorized users.


title: Etiology of viral respiratory infections in Northern Lao People's Democratic Republic

text: In Lao People's Democratic Republic (PDR), acute respiratory infections overburden the health care system, but viral etiology, genetic diversity, and seasonality, especially in light of the introduction of influenza vaccination in the country, are poorly understood. From August 2010 to April 2011, 309 outpatients were recruited at the Luang Prabang Provincial Hospital covering highland Lao communities. Nasopharyngeal swabs were screened for the presence of 13 respiratory viruses. At least one virus was detected in 69.6% and dual/triple viral infections in 12.9%/1.9% of the patients. Influenza A and B viruses combined were the most frequently detected pathogens, followed by human adenovirus and respiratory syncytial virus (RSV). The other viruses were detected in less than 10% of the patients. Phylogenetic analyses on a representative set of RSV strains revealed that, while otherwise very rare, the RSV‐B CB1/THB genotype cocirculated with other common genotypes. A single wave of influenza virus and RSV activity was observed during the rainy season, providing further support to influenza vaccination before the onset of the rains. This study provides recommendations for influenza vaccination that still needs optimization and highlights the need for revised guidelines for treatment and prevention of respiratory infections in Lao PDR, as well as for increased surveillance efforts.


title: Highly Infectious CJD Particles Lack Prion Protein but Contain Many Viral‐Linked Peptides by LC‐MS/MS

text: It is widely believed that host prion protein (PrP), without nucleic acid, converts itself into an infectious form (PrP‐res) that causes transmissible encephalopathies (TSEs), such as human sporadic CJD (sCJD), endemic sheep scrapie, and epidemic BSE. There are many detailed investigations of PrP, but proteomic studies of other proteins in verified infectious TSE particles have not been pursued, even though brain homogenates without PrP retain their complete infectious titer. To define proteins that may be integral to, process, or protect an agent genome, we developed a streamlined, high‐yield purification of infectious FU‐CJD mouse brain particles with minimal PrP. Proteinase K (PK) abolished all residual particle PrP, but did not reduce infectivity, and viral‐size particles lacking PrP were ∼70S (vs. 90–120S without PK). Furthermore, over 1,500 non‐PrP proteins were still present and positively identified in high titer FU‐CJD particles without detectable PrP by mass spectrometry (LC‐MS/MS); 114 of these peptides were linked to viral motifs in the environmental–viral database, and not evident in parallel uninfected controls. Host components were also identified in both PK and non‐PK treated particles from FU‐CJD mouse brain and human sCJD brain. This abundant cellular data had several surprises, including finding Huntingtin in the sCJD but not normal human brain samples. Similarly, the neural Wiskott–Aldrich sequence and multivesicular and endosome components associated with retromer APP (Alzheimer amyloid) processing were only in sCJD. These cellular findings suggest that new therapies directed at retromer–vesicular trafficking in other neurodegenerative diseases may also counteract late‐onset sCJD PrP amyloid pathology. J. Cell. Biochem. 115: 2012–2021, 2014. © 2014 Wiley Periodicals, Inc.


title: Perspectives of patients with rheumatic diseases in the early phase of COVID‐19

text: OBJECTIVE: To determine health perceptions of patients with rheumatic diseases in the early phase of the coronavirus disease 2019 (COVID‐19) pandemic. METHODS: Rheumatology patients at a single centre received via text message the national Rheumatology Association COVID‐19 information sheet and an invitation to participate in a de‐identified survey. Patient concerns regarding risks conferred by their rheumatological disease or medications, impact of receiving the information sheet on the likelihood of staying on medication, and acceptance of telehealth, were ascertained. RESULTS: 2,630 patients received the message and the survey response rate was 21% (n=550). Mean (±SD) age was 52 (±15.2) years and 75% were female. Participants’ highest ranked concern was that their medications would increase their severity of COVID‐19 (76.1%). The highest levels of concern were seen in patients on combination conventional synthetic disease‐modifying anti‐rheumatic drugs (csDMARDs) and/or a biologic/targeted synthetic disease‐modifying anti‐rheumatic drug (b/tsDMARD). There was no association between prednisolone dose and concern. While 63% of patients planned to continue their anti‐rheumatic medications, a further 30% were more likely to stay on their medications as a result of receiving the information. Telehealth was acceptable to 98.4% of patients, but 28.1% felt this was only appropriate while infection control measures were in place. CONCLUSION: Concerns regarding the risk of COVID‐19 among patients on anti‐rheumatic drugs are common. Proactive dissemination of information is needed to address misconceptions relating to medication risk, improve medication adherence and minimise the risk of flares. Telehealth is acceptable to a majority of patients during the COVID‐19 pandemic.


title: Myocarditis caused by Feline Immunodeficiency Virus in Five Cats with Hypertrophic Cardiomyopathy

text: Summary Viral infections have been implicated as the cause of cardiomyopathy in several mammalian species. This study describes hypertrophic cardiomyopathy (HCM) and myocarditis associated with feline immunodeficiency virus (FIV) infection in five cats aged between 1 and 4 years. Clinical manifestations included dyspnoea in four animals, one of which also exhibited restlessness. One animal showed only lethargy, anorexia and vomiting. Necropsy examination revealed marked cardiomegaly, marked left ventricular hypertrophy and pallor of the myocardium and epicardium in all animals. Microscopical and immunohistochemical examination showed multifocal infiltration of the myocardium with T lymphocytes and fewer macrophages, neutrophils and plasma cells. An intense immunoreaction for FIV antigen in the cytoplasm and nucleus of lymphocytes and the cytoplasm of some macrophages was observed via immunohistochemistry (IHC). IHC did not reveal the presence of antigen from feline calicivirus, coronavirus, feline leukaemia virus, feline parvovirus, Chlamydia spp. or Toxoplasma gondii. The results demonstrate the occurrence of FIV infection in inflammatory cells in the myocardium of five cats with myocarditis and HCM.


title: Probable Molecular Mechanism of Remdesivir for the Treatment of COVID-19: Need to Know More

text: Abstract COVID-19 is now pandemic throughout the world. Scientist, doctors are searching for effective therapy of this diseases. The remdesivir, an antiviral drug, is appeared as ‘molecule of hope’ for the treatment of this disease. USFDA approve this drug for the treatment of COVID-19. The molecular mechanism is unknown. In this paper, we tried to describe the probable molecular mechanism of remdesivir to inhibit the RNA synthesis of SARS-CoV-2. However, more detail mechanism is needed to understand mechanism of action of remdesivir.


title: Pulmonary Edema in COVID19—A Neural Hypothesis

text: In COVID-19, lung manifestations present as a slowly evolving pneumonia with insidious early onset interstitial pulmonary edema that undergoes acute exacerbation in the late stages and microvascular thrombosis. Currently, these manifestations are considered to be only consequences of pulmonary SARS-CoV-2 virus infection. We are proposing a new hypothesis that neurogenic insult may also play a major role in the pathogenesis of these manifestations. SARS-CoV-2 mediated inflammation of the nucleus tractus solitarius (NTS) may play a role in the acute exacerbation of pulmonary edema and microvascular clotting in COVID-19 patients.


Editorial: Moving Pieces in Molecular Immunology


title: Marine Algal Antioxidants as Potential Vectors for Controlling Viral Diseases

text: As the COVID-19 epidemic expands in the world, and with the previous SARS epidemic, avian flu, Ebola and AIDS serving as a warning, biomedical and biotechnological research has the task to find solutions to counteract viral entry and pathogenesis. A novel approach can come from marine chemodiversity, recognized as a relevant source for developing a future natural “antiviral pharmacy”. Activities of antioxidants against viruses can be exploited to cope with human viral infection, from single individual infections to protection of populations. There is a potentially rich and fruitful reservoir of such compounds thanks to the plethora of bioactive molecules and families present in marine microorganisms. The aim of this communication is to present the state-of-play of what is known on the antiviral activities recognized in (micro)algae, highlighting the different molecules from various algae and their mechanisms of actions, when known. Given the ability of various algal molecules—mainly sulfated polysaccharides—to inhibit viral infection at Stage I (adsorption and invasion of cells), we envisage a need to further investigate the antiviral ability of algae, and their mechanisms of action. Given the advantages of microalgal production compared to other organisms, the opportunity might become reality in a short period of time.


title: International Expansion of a Novel SARS-CoV-2 Mutant

text: RNA viruses such as coronavirus are rapidly evolving pathogens that can accumulate considerable genetic diversity in relatively short time periods.….


MHV-A59 Orf1a Replicase Protein NSP7-NSP10 Processing in Replication


LIGHTS AND SHADOWS OF SARS-CoV-2 INFECTION RISK ASSESSMENT IN ENDOSCOPY


title: De Novo Design of α-Helical Lipopeptides Targeting Viral Fusion Proteins: A Promising Strategy for Relatively Broad-Spectrum Antiviral Drug Discovery

text: [Image: see text] Class I enveloped viruses share similarities in their apparent use of a hexameric coiled-coil assembly to drive the merging of virus and host cell membranes. Inhibition of coiled coil-mediated interactions using bioactive peptides that replicate an α-helical chain from the viral fusion machinery has significant antiviral potential. Here, we present the construction of a series of lipopeptides composed of a de novo heptad repeat sequence-based α-helical peptide plus a hydrocarbon tail. Promisingly, the constructs adopted stable α-helical conformations and exhibited relatively broad-spectrum antiviral activities against Middle East respiratory syndrome coronavirus (MERS-CoV) and influenza A viruses (IAVs). Together, these findings reveal a new strategy for relatively broad-spectrum antiviral drug discovery by relying on the tunability of the α-helical coiled-coil domains present in all class I fusion proteins and the amphiphilic nature of the individual helices from this multihelix motif.


title: Performance of a commercial assay for detecting and quantifying HEV RNA in faeces

text: Abstract Background Detecting hepatitis E virus (HEV) RNA in faeces is useful for diagnosing and monitoring HEV infections, particularly in immunocompromised patients requiring ribavirin therapy. Objectives This study evaluated the performance of the Altona RealStar HEV RNA kit for detecting and quantifying HEV in faeces. Study design RNA was extracted from 94 stool samples by two methods: QIAamp Viral RNA Mini kit and MagNA Pure 96 automate. The Altona results were compared to a reference laboratory-developed accredited ISO15189 RT-PCR assay. Results The Altona and reference assays detect HEV RNA in 77/93 (82.8%) and 83/93 (89.2%) of the QIAamp extracted samples, respectively, after exclusion of invalid result; they detected HEV RNA in 67/92 (72.8%) and 66/92 (71.7%) of the MagNA Pure extracted samples, respectively, which emphasizes the importance of the RNA extraction method. The HEV RNA concentrations obtained with Altona RT-PCR and the reference RT-PCR were well correlated whatever the extraction method, and Bland Altman analyses indicated that the Altona values were higher than the reference assay values. The Altona values for QIAamp-extracted and MagNA Pure-extracted HEV RNA were very similar. Conclusions The Altona RealStar assay is suitable for quantifying HEV RNA in the faeces and monitoring HEV RNA shedding during ribavirin therapy. Extraction is critical for detecting faecal HEV with high performance RT-PCR assays.


title: Idiopathic polyradiculoneuropathy in a Bengal cat: electrophysiological findings and 1 year follow-up

text: This report describes a rapidly progressive loss of motor function in a 16-month-old male neutered Bengal cat, beginning in the pelvic limbs and progressing to involve all limbs and rendering the cat non-ambulatory. The neurological examination revealed flaccid tetraparesis with decreased spinal reflexes but preserved conscious proprioception and skin sensation. Extensive electrophysiological tests were conducted including electromyography, motor and sensory peripheral nerves potential recordings and ‘late’ potentials, defining the electrodiagnostic characteristics of this disease. Based on the electrophysiological findings, a generalised proximal and predominantly axonal neuropathy affecting the ventral (motor) nerve roots was suspected. As no aetiology was identified, this disease was classified as idiopathic polyradiculoneuropathy. Over a year, the cat presented three separate episodes of tetraparesis, each with a spontaneous complete recovery, consistent with the reportedly good prognosis for this disease.


Answering the Call: Medical Students Reinforce Health System Frontlines Through Ochsner COVID-19 Hotline


title: Traditional Chinese herbal medicine for treating novel coronavirus (COVID-19) pneumonia: protocol for a systematic review and meta-analysis

text: BACKGROUND: A new type of coronavirus, novel coronavirus (COVID-19), is causing an increasing number of cases of pneumonia and was declared a Public Health Emergency of International Concern by the World Health Organization on 30 January 2020. The virus first appeared in Wuhan, China, in late December 2019, and traditional Chinese herbal medicine is being used for its treatment. This systematic review and meta-analysis will assess studies of the effects of traditional Chinese herbal medicine in COVID-19 pneumonia. METHODS: We will search electronic databases including PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), and Wanfang database using keywords related to COVID-19 and traditional Chinese herbal medicine. Reference lists of relevant trials and reviews will be searched. We will manually search gray literature, such as conference proceedings and academic degree dissertations, and trial registries. Two independent reviewers will screen studies (XL and DZ), extract data (YL and LG), and evaluate risk of bias (YL and DZ). Data analysis will be conducted using the Review Manager software (version 5.3.5) and R software (version 3.6.1). Statistical heterogeneity will be assessed using a standard chi-square test with a significance level of P < 0.10. Biases associated with study size (e.g., publication bias) will be investigated using funnel plots, Egger’s test and Begg’s test, and Trim and Fill analysis. DISCUSSION: This study will provide a high-quality synthesis of the effects of traditional Chinese herbal medicine for COVID-19. The use of traditional Chinese herbal medicine for treatment or prevention of these novel viral infections affecting the pneumonia will be investigated. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number: CRD42020168004


Chronic obstructive pulmonary disease and the COVID-19 pandemic: reciprocal challenges


title: Animal and plant cell technology: A critical evaluation of the technology/society interface

text: The rate at which technology progresses is dependent on the nature of the technology/society interface. This is a complex interaction which involves the production of people capable of making technical advances, the physical opportunities for the deployment of those trained individuals in this task as well as cultural and social factors which will motivate the innovators to produce the advances we need to maintain the momentum of our continually improving situation. One particular aspect of the social situation which may be singled out for special attention is that of the ethics of the society in which people make and use the products of the innovation process. The ethical aspects of biotechnological activities has commanded a great deal of attention recently both from the professional and societal stake-holders. This paper, therefore examines in some detail the ethical aspects of the technology/society interface as it applies, in particular, to the development of animal and plant cell biotechnology. It focuses on the role of the regulatory agency and on the need for biotechnologists to acquire professional status so that they may develop a more trustworthy relationship with society.


title: General concepts of virology

text: A basic understanding of viruses and how they replicate and produce disease can aid in the management of virus infections. Parameters, such as clinical signs, sample and test selection, prognosis, and control, are implicit in this understanding. Information increases almost daily about known and emerging viruses; this impacts our ability to manage and control infections.