title: Targeting the Vasoprotective Axis of the Renin-Angiotensin System: A Novel Strategic Approach to Pulmonary Hypertensive Therapy

text: A decade has passed since the discovery of angiotensin-converting enzyme 2 (ACE2), a component of the ACE2–angiotensin (Ang)-(1-7)–Mas counterregulatory axis of the renin angiotensin system (RAS). ACE2 is considered an endogenous regulator of the vasoconstrictive, proliferative, fibrotic, and proinflammatory effects of the ACE–Ang II–angiotensin II type 1 receptor (AT(1)R) axis. Both animal and clinical studies have emerged to define a role for ACE2 in pulmonary arterial hypertension (PAH). There is scientific evidence supporting the concept that ACE2 maintains the RAS balance and plays a protective role in PAH. The activation of pulmonary ACE2 could influence the pathogenesis of PAH and serve as a novel therapeutic target in PAH. Current therapeutic strategies and interventions have limited success, and PAH remains a fatal disease. Thus, more research that establishes the novel therapeutic potential and defines the mechanism of the ACE2–Ang-(1-7)–Mas counterregulatory axis in PAH is needed.


title: Comment et pourquoi adapter le masque Décathlon EasyBreath® pour les soignants prenant en charge des patients infectés par le SARS-CoV-2?

text: Résumé Durant l’épidémie de COVID-19, les équipements de protection personnelle sont largement utilisés pour limiter l’infection des soignants. Des solutions innovantes ont été décrites pour pallier les difficultés d’approvisionnement. L’adaptation du masque de plongée EasyBreath® par l’équipe de Prakash a été médiatisée et diffusée. Nous présentons 4 dispositifs imprimés en 3D que nous avons modifiés par rapport au design initial innovant afin de nous adapter aux contraintes locales. Nous avons testé le masque en condition chirurgicale. Les modifications apportées garantissent une meilleure ergonomie, visibilité et capacités de communication, mais elles n’ont pas d’homologation d’utilisation et ne peuvent donc être recommandées qu’en l’absence de solution alternative validée. L’impression 3D est un outil de première importance dans la production de dispositifs à usage médical en situation de crise sanitaire.


title: Respiratory virus infections: Understanding COVID-19

text: Respiratory viruses affect us throughout our lives, from infancy to old age, causing illnesses ranging from a common cold to severe pneumonia. They belong to several virus families, and although many features of infection with these diverse viruses are shared, some have unique characteristics. Here we explain what happens when we are infected by respiratory viruses, including SARS-CoV-2, which causes COVID-19.


title: Chapter 20 Reproductive management of poultry

text: Abstract Based on data from the UN's Food and Agricultural Organization, about 120 million metric tons of poultry meat were produced globally in 2016. In addition, about 82 million metric tons of eggs were produced. One of the bases for this production is the reproductive efficiency of today's poultry. This, in turn, is due to their inherent reproductive physiology, intensive genetic selection and advances in husbandry/management. The system of reproduction in males in largely similar to that in mammals except that there is no descent of testes. In females, there are marked differences with there being a single ovary and oviduct; the latter being the name of the differentiated entire Müllerian duct. Moreover, females produce eggs with a yolky oocyte surrounded by albumen, membranes and shell. Among the most successful reproductive management techniques are optimizing photoperiod, light intensity and nutrition. Widespread employment of these has allowed maximizing production. Laying hens can be re-cycled toward the end egg production. Other aspects of reproductive management in poultry include the following: artificial insemination (almost exclusively employed in turkeys) and approaches to reduce broodiness together with cage free (colony), conventional, enriched and free-range systems.


title: COVID-19 impact assessment on the French radiological centers: a nationwide survey

text: PURPOSE: To determine the impact of the COVID-19 on the CT activities in French radiological centers during the epidemic peak. MATERIALS AND METHODS: A cross-sectional prospective CT scan survey was conducted between March 16 and April 12, 2020, in accordance with the local IRB. Seven hundred nine radiology centers were invited to participate in a weekly online survey. Numbers of CT examinations related to COVID-19 including at least chest (CT(covid)) and whole chest CT scan activities (CT(chest)) were recorded each week. A sub-analysis on French departments was performed during the 4 weeks of the study. The impact of the number of RT-PCRs (reverse transcriptase polymerase chain reactions) on the CT workflow was tested using two-sample t test and Pearson’s test. RESULTS: Five hundred seventy-seven structures finally registered (78%) with mean response numbers of 336 ± 18.9 (323; 351). Mean CT(chest) activity per radiologic structure ranged from 75.8 ± 133 (0–1444) on week 12 to 99.3 ± 138.6 (0–1147) on week 13. Mean ratio of CT(covid) on CT(chest) varied from 0.36 to 0.59 on week 12 and week 14 respectively. There was a significant relationship between the number of RT-PCR performed and the number of CT(covid) (r = 0.73, p = 3.10(−16)) but no link with the number of positive RT-PCR results. CONCLUSION: In case of local high density COVID-19, CT workflow is strongly modified and redirected to the management of these specific patients. KEY POINTS: • Over the 4-week survey period, 117,686 chest CT (CT (total) ) were performed among the responding centers, including 61,784 (52%) CT performed for COVID-19 (CT (covid) ). • Across the country, the ratio CT (covid) /CT (total) varied from 0.36 to 0.59 and depended significantly on the local epidemic density (p = 0.003). • In clinical practice, in a context of growing epidemic, in France, chest CT was used as a surrogate to RT-PCR for patient triage. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00330-020-07035-w) contains supplementary material, which is available to authorized users.


title: A multisite, randomized field trial to evaluate the influence of lactoferrin on the morbidity and mortality of dairy calves with diarrhea

text: ABSTRACT Diarrhea is one of the most common causes of antimicrobial use and mortality in young calves. To reduce antimicrobial use and resistance on dairy farms, research on alternative therapies for calf diarrhea is necessary. Our laboratory previously conducted a randomized clinical trial investigating the effectiveness of lactoferrin, an iron-binding protein found in colostrum, as a treatment for calf diarrhea. The trial showed significantly reduced calf mortality in diarrheic calves that were administered lactoferrin. Thus, the objective of this study was to corroborate the results of our prior clinical trial across multiple farms and to investigate the effect of lactoferrin on the morbidity and mortality of preweaned calves with naturally occurring cases of diarrhea. This randomized field trial was conducted on 5 commercial dairy farms in Ohio. In total, 485 calves (≤21 d of age) were enrolled at first diarrhea diagnosis (fecal score ≥2 defined as loose to watery) and randomly assigned to receive an oral dose of lactoferrin (3 g of lactoferrin powder dissolved in 30 mL of water) or 30 mL of water (control) once daily for 3 consecutive days. Health assessments were conducted on the day of diarrhea diagnosis (d 0) and 1, 2, 3, 7, 14, 21, 28, and 35 d following diagnosis. Producer records of disease treatment and mortality were collected 120 d following diagnosis. A Poisson regression model was used to test differences between treatments in disease frequency through 35 d post-diarrhea diagnosis and the incidence risk of treatment and mortality risk 120 d post-diarrhea diagnosis; the model controlled for calf age at enrollment, farm, and treatment. Median calf age at enrollment was 11 d and ranged from 1 to 26 d of age. At study enrollment, 51.3% (123/240) and 52.2% (128/245) of calves in the control and lactoferrin treatment groups, respectively, were diagnosed with severe diarrhea (fecal score = 3). The frequency of disease (diarrhea, dehydration, depression, signs of respiratory disease) through 35 d following diarrhea diagnosis was not significantly different for calves in the lactoferrin and control groups. Overall mortality risk for enrolled calves was 9.9%, and 10.7% (22/243) and 9.1% (26/242) of calves in the lactoferrin and control groups, respectively, died or were culled in the 120 d following diarrhea diagnosis. The relative risk of death or culling did not differ between treatment groups, however. Therefore, as performed in this study, lactoferrin as a treatment for calf diarrhea was not beneficial.


title: RNA structures with pseudo-knots: Graph-theoretical, combinatorial, and statistical properties

text: The secondary structures of nucleic acids form a particularly important class of contact structures. Many important RNA molecules, however, contain pseudo-knots, a structural feature that is excluded explicitly from the conventional definition of secondary structures. We propose here a generalization of secondary structures incorporating ‘non-nested’ pseudo-knots, which we call bi-secondary structures, and discuss measures for the complexity of more general contact structures based on their graph-theoretical properties. Bi-secondary structures are planar trivalent graphs that are characterized by special embedding properties. We derive exact upper bounds on their number (as a function of the chain length n) implying that there are fewer different structures than sequences. Computational results show that the number of bi-secondary structures grows approximately like 2.35(n). Numerical studies based on kinetic folding and a simple extension of the standard energy model show that the global features of the sequence-structure map of RNA do not change when pseudo-knots are introduced into the secondary structure picture. We find a large fraction of neutral mutations and, in particular, networks of sequences that fold into the same shape. These neutral networks percolate through the entire sequence space.


title: Characterization of pantropic canine coronavirus from Brazil

text: Abstract Characterization of canine coronavirus (CCoV) strains currently in circulation is essential for understanding viral evolution. The aim of this study was to determine the presence of pantropic CCoV type IIa in tissue samples from five puppies that died in Southern Brazil as a result of severe gastroenteritis. Reverse-transcriptase PCR was used to generate amplicons for sequence analysis. Phylogenetic analysis of the CCoV-IIa strains indicated that they were similar to those found in other countries, suggesting a common ancestor of these Brazilian isolates. This is the first report of pantropic CCoV-II in puppies from Latin America and our findings highlight that CCoV should be included as a differential diagnosis when dogs present with clinical signs and lesions typically seen with canine parvovirus infection.


title: The Threat and Response to Infectious Diseases (Revised)

text: The threat from microorganisms is complex, and the approaches for reducing the challenges the world is facing are also multifaceted, but a combination approach including several simple steps can make a difference and reduce morbidity and mortality and the economic cost of fighting infectious diseases. This paper discusses the continually evolving infectious disease landscape, contributing factors in the rise of the threat, reasons for optimism, and the policies, technologies, actions, and institutions that might be harnessed to further reduce the dangers introduced by pathogens. It builds upon and updates the work of other authors that have recognized the dangers of emerging and re-emerging pathogens and have explored and documented potential solutions.


title: Critical reviews of immunotheranostics

text: Immunity is the most critical and well-regulated protection to the body. Immunity is implicated in a wide range of diseases and serves as the foundation for immunotherapy. Immunotheranostics is the idea of improving immunotherapy through the organic integration of therapeutic, diagnostic, and screening technologies. This special issue collects reviews and opinions from prominent contributors in the immunotheranostic field who represent highly diversified research expertise. The immunotherapeutics discussed in this issue range from small molecules, peptides, antibodies, nanoparticles, and to cells. Discussions from the therapeutic development perspective are accompanied by opinions from the biology and medicine aspects. Further, there are reviews about different types of imaging technologies and their applications in immunotherapy. Lastly, one review raises attention to mass spectrometry for its utilization in the diagnosis and assessment for immunotherapy. In summary, this special issue is a showcase for what is happening in immunotheranostics. Moreover, it is also a justified wish list for what should and will happen in immunotheranostics.


title: RNA silencing of rotavirus gene expression

text: Abstract RNA interference (RNAi) is a double-stranded RNA (dsRNA)-triggered mechanism for suppressing gene expression, which is conserved in evolution and has emerged as a powerful tool to study gene function. Rotaviruses, the leading cause of severe diarrhea in young children, are formed by three concentric layers of protein, and a genome composed of 11 segments of dsRNA. Here, we show that the RNAi machinery can be triggered to silence rotavirus gene expression by sequence-specific short interfering RNAs (siRNAs). RNAi is also useful for the study of the virus-cell interactions, through the silencing of cellular genes that are potentially important for the replication of the virus. Interestingly, while the translation of mRNAs is readily stopped by the RNAi machinery, the viral transcripts involved in virus genome replication do not seem to be susceptible to RNAi. Since gene silencing by RNAi is very efficient and specific, this system could become a novel therapeutic approach for rotavirus and other virus infections, once efficient methods for in vivo delivery of siRNAs are developed. Although the use of RNAi as an antiviral therapeutic tool remains to be demonstrated, there is no doubt that this technology will influence drastically the way postgenomic virus research is conducted.


title: Detection and genetic characterization of Mamastrovirus 5 from Brazilian dogs

text: Mamastrovirus 5 (MAstV5), belonging to the Astroviridae (AstV) family, previously known as canine astrovirus or astrovirus-like particles, has been reported in several countries to be associated with viral enteric disease in dogs since the 1980s. Astroviruses have been detected in fecal samples from a wide variety of mammals and birds that are associated with gastroenteritis and extra enteric manifestations. In the present study, RT-PCR was used to investigate the presence of MAstV5 in 269 dog fecal samples. MAstV5 was detected in 26% (71/269) of the samples. Interestingly, all MAstV5-positive samples derived from dogs displaying clinical signs suggestive of gastroenteritis, other enteric viruses were simultaneously detected (canine parvovirus, canine distemper virus, canine coronavirus, canine adenovirus and canine rotavirus). Based on genomic sequence analysis of MAstV5 a novel classification of the species into four genotypes, MAstV5a-MAstV5d, is proposed. Phylogenetic analyses based on the ORF2 amino acid sequences, samples described herein grouped into the putative genotype ‘a’ closed related with Chinese samples. Other studies are required to attempt the clinical and antigenic implications of these astrovirus genotypes in dogs.


title: Combined approaches of EPR and NMR illustrate only one transmembrane helix in the human IFITM3

text: Interferon-inducible transmembrane protein IFITM3 was known to restrict the entry of a wide spectrum of viruses to the cytosol of the host. The mechanism used by the protein to restrict viral entry is unclear given the unavailability of the membrane topology and structures of the IFITM family proteins. Systematic site-directed spin labeling (SDSL) and electron paramagnetic resonance (EPR) studies of IFITM3 in detergent micelles identified a single, long transmembrane helix in the C-terminus and an intramembrane segment in the N-terminal hydrophobic region. Solution NMR studies of the same sample verified the secondary structure distribution and demonstrated two rigid regions interacting with the micellar surface. The resulting membrane topology of IFITM3 supports the mechanism of an enhanced restricted membrane hemi-fusion.


title: Mechanisms of Cellular Membrane Reorganization to Support Hepatitis C Virus Replication

text: Like all positive-sense RNA viruses, hepatitis C virus (HCV) induces host membrane alterations for its replication termed the membranous web (MW). Assembling replication factors at a membranous structure might facilitate the processes necessary for genome replication and packaging and shield viral components from host innate immune defenses. The biogenesis of the HCV MW is a complex process involving a concerted effort of HCV nonstructural proteins with a growing list of host factors. Although a comprehensive understanding of MW formation is still missing, a number of important viral and host determinants have been identified. This review will summarize the recent studies that have led to our current knowledge of the role of viral and host factors in the biogenesis of the MWs and discuss how HCV uses this specialized membrane structure for its replication.


title: COVID-19 coronavirus: recommended personal protective equipment for the orthopaedic and trauma surgeon

text: PURPOSE: With the COVID-19 crisis, recommendations for personal protective equipment (PPE) are necessary for protection in orthopaedics and traumatology. The primary purpose of this study is to review and present current evidence and recommendations for personal protective equipment and safety recommendations for orthopaedic surgeons and trauma surgeons. METHODS: A systematic review of the available literature was performed using the keyword terms “COVID-19”, “Coronavirus”, “surgeon”, “health-care workers”, “protection”, “masks”, “gloves”, “gowns”, “helmets”, and “aerosol” in several combinations. The following databases were assessed: Pubmed, Cochrane Reviews, Google Scholar. Due to the paucity of available data, it was decided to present it in a narrative manner. In addition, participating doctors were asked to provide their guidelines for PPE in their countries (Austria, Luxembourg, Switzerland, Germany, UK) for consideration in the presented practice recommendations. RESULTS: World Health Organization guidance for respiratory aerosol-generating procedures (AGPs) such as intubation in a COVID19 environment was clear and included the use of an FFP3 (filtering face piece level 3) mask and face protection. However, the recommendation for surgical AGPs, such as the use of high-speed power tools in the operating theatre, was not clear until the UK Public Health England (PHE) guidance of 27 March 2020. This guidance included FFP3 masks and face protection, which UK surgeons quickly adopted. The recommended PPE for orthopaedic surgeons, working in a COVID19 environment, should consist of level 4 surgical gowns, face shields or goggles, double gloves, FFP2-3 or N95-99 respirator masks. An alternative to the mask, face shield and goggles is a powered air-purifying respirator, particularly if the surgeons fail the mask fit test or are required to undertake a long procedure. However, there is a high cost and limited availabilty of these devices at present. Currently available surgical helmets and toga systems may not be the solution due to a permeable top for air intake. During the current COVID-19 crisis, it appeared that telemedicine can be considered as an electronic personal protective equipment by reducing the number of physical contacts and risk contamination. CONCLUSION: Orthopaedic and trauma surgery using power tools, pulsatile lavage and electrocautery are surgical aerosol-generating procedures and all body fluids contain virus particles. Raising awareness of these issues will help avoid occupational transmission of COVID-19 to the surgical team by aerosolization of blood or other body fluids and hence adequate PPE should be available and used during orthopaedic surgery. In addition, efforts have to be made to improve the current evidence in this regard. LEVEL OF EVIDENCE: IV.


title: SARS‐CoV‐2, bacterial co‐infections, and AMR: the deadly trio in COVID‐19?

text: At the end of December 2019, Chinese public health authorities reported a cluster of pneumonia of unknown cause in central city of Wuhan in Hubei province. Shortly after, Chinese scientists identified a hitherto undescribed beta‐coronavirus as the likely causative agent. The disease is now referred to as coronavirus disease 2019 (COVID‐19), and the virus is called severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Since 31 December 2019 and as of 25 May 2020, 5,432,512 cases of COVID‐19 (in accordance with the applied case definitions and testing strategies in the affected countries) have been reported globally, including 345,467 deaths.


title: Chapter 9 Vaccines and Immunotherapy

text: Abstract This chapter examines the general topic of vaccines. The goal is to develop a perspective on active and passive immunization for vaccination against infectious agents of multiple classes. A discussion also will demonstrate how principles in immunology combine with biotechnology to advance the field of vaccinology.


title: COVID 19 and heart failure: from infection to inflammation and angiotensin II stimulation. Searching for evidence from a new disease

text: Patients with cardiovascular disease and, namely, heart failure are more susceptible to coronavirus disease 2019 (COVID‐19) and have a more severe clinical course once infected. Heart failure and myocardial damage, shown by increased troponin plasma levels, occur in at least 10% of patients hospitalized for COVID‐19 with higher percentages, 25%–35% or more, when patients critically ill or with concomitant cardiac disease are considered. Myocardial injury may be elicited by multiple mechanisms, including those occurring with all severe infections, such as fever, tachycardia, adrenergic stimulation, as well as those caused by the exaggerated inflammatory response, endotheliitis and, in some cases, myocarditis that have been shown in patients with COVID‐19. A key role may be that of the renin–angiotensin‐aldosterone system. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infects human cells binding to angiotensin‐converting‐enzyme 2 (ACE2), an enzyme responsible of the cleavage of angiotensin II into angiotensin 1–7, which has vasodilating and anti‐inflammatory effects. Virus‐mediated downregulation of ACE2 may increase angiotensin II stimulation and contribute to the deleterious hyper‐inflammatory reaction of COVID‐19. On the other hand, ACE2 may be upregulated in patients with cardiac disease and treated with ACE inhibitors or angiotensin receptor blockers. ACE2 upregulation may increase the susceptibility to COVID‐19 but may be also protective versus angiotensin II mediated vasoconstriction and inflammatory activation. Recent data show the lack of untoward effects of ACE inhibitors or angiotensin receptor blockers for COVID‐19 infection and severity. Prospective trials are needed to ascertain whether these drugs may have protective effects. This article is protected by copyright. All rights reserved.


title: Virus diffusion in isolation rooms

text: Summary In hospitals, the ventilation of isolation rooms operating under closed-door conditions is vital if the spread of viruses and infection is to be contained. Engineering simulation, which employs computational fluid dynamics, provides a convenient means of investigating airflow behaviour in isolation rooms for various ventilation arrangements. A cough model was constructed to permit the numerical simulation of virus diffusion inside an isolation room for different ventilation system configurations. An analysis of the region of droplet fallout and the dilution time of virus diffusion of coughed gas in the isolation room was also performed for each ventilation arrangement. The numerical results presented in this paper indicate that the parallel-directional airflow pattern is the most effective means of controlling flows containing virus droplets. Additionally, staggering the positions of the supply vents at the door end of the room relative to the exhaust vents on the wall behind the bed head provides effective infection control and containment. These results suggest that this particular ventilation arrangement enhances the safety of staff when performing medical treatments within isolation rooms.


Susceptibility to Upper Respiratory Tract Infection and Touching of the Eyes or Nose: A Cross‐sectional Study of Japanese Workers: Yasushi FUKUNAKA, et al. Department of Safety and Health, Tokyo Gas Co., Ltd.— OBJECTIVES: This study was a cross‐sectional survey of Japanese workers regarding the relationship between touching the eyes or nose and susceptibility to URTI in workers. METHODS: The survey respondents were 4,663 Japanese workers. Subjects were surveyed via a self‐administered questionnaire regarding their susceptibility to URTI and how often they touched their eyes or nose. In addition, subjects were surveyed regarding their preventive behaviors and routine behaviors thought to be associated with URTIs. A multiple logistic regression model was used to assess the relationship between susceptibility to URTI and how often the eyes or nose are touched. RESULTS: Responses from 3,663 individuals who answered the self‐administered questionnaire were analyzed. There were 1,590 individuals (42.9%) with a “frequent incidence of URTIs”, defined as URTIs more than once a year. In terms of how often the eyes or nose are touched, the odds ratios (95% CI) for a frequent incidence of URTIs among the groups responding “sometimes” and “often” were 1.41 (1.21−1.63) and 1.96 (1.59−2.42) (trend test: p<0.001) compared with the groups responding “never” and “almost never”. Multivariate‐adjusted odds ratios adjusted for confounding factors, i.e., behaviors to prevent URTIs, routine behaviors associated with URTIs, age, sex and BMI, were 1.33 (1.14−1.54) and 1.69 (1.36−2.09) (trend test: p<0.001). CONCLUSIONS: The present cross‐sectional study indicates that susceptibility to URTI and how often the eyes or nose are touched are significantly associated in Japanese workers, independent of preventive behaviors and routine behaviors associated with URTIs.


First, do no harm: Lessons learned from a storytelling event for pediatric residents during the COVID-19 pandemic


title: Alterations in Gut Microbiota of Patients With COVID-19 During Time of Hospitalization

text: Abstract BACKGROUD & AIMS: Although SARS-CoV-2 infects gastrointestinal tissues, little is known about the roles of gut commensal microbes in susceptibility to and severity of infection. We investigated changes in fecal microbiomes of patients with SARS-CoV-2 infection during hospitalization and associations with severity and fecal shedding of virus. METHODS We performed shotgun metagenomic sequencing analyses of fecal samples from 15 patients with COVID-19 in Hong Kong, from February 5 through March 17, 2020. Fecal samples were collected 2 or 3 times per week from time of hospitalization until discharge; disease was categorized as mild (no radiographic evidence of pneumonia), moderate (pneumonia was present), severe (respiratory rate ≥30/min, or oxygen saturation ≤93% when breathing ambient air), or critical (respiratory failure requiring mechanical ventilation, shock, or organ failure requiring intensive care). We compared microbiome data with those from 6 subjects with community-acquired pneumonia and 15 healthy individuals (controls). We assessed gut microbiome profiles in association with disease severity and changes in fecal shedding of SARS-CoV-2. RESULTS Patients with COVID-19 had significant alterations in fecal microbiomes compared with controls, characterized by enrichment of opportunistic pathogens and depletion of beneficial commensals, at time of hospitalization and at all timepoints during hospitalization. Depleted symbionts and gut dysbiosis persisted even after clearance of SARS-CoV-2 (determined from throat swabs) and resolution of respiratory symptoms. The baseline abundance of Coprobacillus, Clostridium ramosum, and Clostridium hathewayi correlated with COVID-19 severity; there was an inverse correlation between abundance of Faecalibacterium prausnitzii (an anti-inflammatory bacterium) and disease severity. Over the course of hospitalization, Bacteroides dorei, Bacteroides thetaiotaomicron, Bacteroides massiliensis, and Bacteroides ovatus, which downregulate expression of ACE2 in murine gut, correlated inversely with SARS-CoV-2 load in fecal samples from patients. CONCLUSIONS In a pilot study of 15 patients with COVID-19, we found persistent alterations in the fecal microbiome during the time of hospitalization, compared with controls. Fecal microbiota alterations were associated with fecal levels of SARS-CoV-2 and COVID-19 severity. Strategies to alter the intestinal microbiota might reduce disease severity.


title: Detection of human coronavirus NL63 in young children with bronchiolitis

text: HCoV‐NL63, the fourth human coronavirus, has been isolated recently from children with respiratory tract infections, including upper respiratory infection, bronchiolitis, and pneumonia. The virus has been also detected in immunocompromised adults with respiratory tract infections. A total of 118 nasopharyngeal swab samples from 118 hospitalized young children aged less than 2 years with bronchiolitis who were not infected with human respiratory syncytial virus, influenza A or B, or human metaneumovirus were selected. Three (2.5%) of the 118 samples were positive for HCoV‐NL63 by reverse transcription‐polymerase chain reaction tests. HCoV‐NL63 may be one of the causative agents of bronchiolitis in young children. J. Med. Virol. 75:463–465, 2005. © 2005 Wiley‐Liss, Inc.


title: Diagnostic Techniques: Microarrays

text: Current techniques for viral detection and discovery, which include culture and serological methods as well as polymer chain reaction (PCR)-based protocols, possess a variety of inherent limitations. In an effort to augment the capabilities of existing diagnostic methodologies, the use of virus-specific DNA microarray technology has been recently applied in both research and clinical settings with favorable results. The primary advantage of this approach is that DNA microarrays containing literally thousands of virus-specific sequences allow simultaneous testing for essentially all known viral species. While previous methods have been limited to testing for a single pathogen, or small numbers of specific pathogens, a panviral assay is less biased and can be designed to detect variant or even novel members of existing viral families. The use of DNA microarrays in both research and clinical settings has the potential to substantially increase the number of instances in which a virus may be identified in biological samples. With the proper bioinformatics methodologies, this technology will also maximize the probability that previously uncharacterized pathogens are detected potentially leading to an improved understanding of the etiology for many chronic human diseases. This article focuses on all aspects of virus-specific DNA microarray implementation, from array design to sample processing, amplification, and data analysis.


Immunoblot analysis of antiAChR antibodies in myasthenia gravis


title: Chapter 6 Circulation of respiratory pathogens at mass gatherings, with special focus on the Hajj pilgrimage

text: Abstract A major public health concern in relation to mass gatherings is the international circulation of infectious diseases, and the spread between participants and to the population of the nation hosting the event. Transmission of respiratory pathogens at the Hajj Muslim pilgrimage in the Kingdom of Saudi Arabia is highly frequent, resulting in high acquisition rates of virus and bacteria carriage. The Hajj may, therefore, contribute to the globalization of common respiratory pathogens resulting from the cross-contamination of participants harboring pathogens that easily spread among pilgrims. A wide range of viral and bacterial clinical infections of the upper and lower respiratory tract can occur during the Hajj, leading to a high number of outpatient consultations and hospitalization in Saudi hospitals. Although outbreaks are less frequently reported in or after mass gatherings, they do sometimes occur, resulting in the international spread of measles, influenza, and mumps.


title: Neurosurgery Practice During Coronavirus Disease 2019 (COVID-19) Pandemic

text: Abstract Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a highly contagious, life-threatening condition with unprecedented impacts for worldwide societies and healthcare systems. Since the first detection in China, it has spread rapidly worldwide. The increased burden has substantially impacted the neurosurgery practice and intensive modifications were required in surgical scheduling, inpatient and outpatient clinics, management of emergency cases, and even academic activities. In some systems, non-overlapping teams were created to minimize transmission among healthcare workers. In case of a massive burden, neurosurgeons may be needed to reassign to the COVID-19 wards, or teams from other regions may be needed to send to severely affected areas. In outpatient practice, if possible, appointments should be turned into telemedicine. All staff assigned in the non-COVID treatment unit should be clothed in level 1 personal protective equipment. If possible, postponement is recommended for operations that do not require urgent or emergent intervention. All patients indicated for surgery must receive a COVID-19 screening, including nasopharyngeal swab, and thorax computed tomography. Level 2 protection measures would be appropriate during COVID-19 negative patients' operations. Operations of COVID-19 positive patients, and emergency cases, where screening can not be obtained, should be performed following level 3 protective measures. During surgery, the use of high-speed drills and electrocautery should be reduced to minimize aerosol production. Screening is crucial in all patients since the surgical outcome is highly mortal in COVID-19 patients. All educational and academic conferences can be turned into virtual webinars.


Detection of human bocavirus in Asturias, Northern Spain


title: Protección de los profesionales sanitarios en nefrologia ante la pandemia por COVID-19

text: RESUMEN La epidemia de COVID19 representa un riesgo especial para los pacientes renales por sus comorbilidades y edad avanzada, y por la realización del tratamiento de hemodiálisis en salas colectivas, pero también supone un riesgo para los profesionales responsables de su atención. El presente manuscrito recoge una propuesta de actuación para prevenir la infección entre los profesionales en los Servicios de Nefrología. SUMMARY The COVID19 epidemic represents a special risk for kidney patients due to their comorbidities and advanced age, and the need for hemodialysis treatment in group rooms. It also represents a risk for professionals responsible for their attention. This manuscript contains a proposal for action to prevent infection of professionals in the Nephrology Services, one of the most valuable assets at the present time.


title: How a Psychopharmacology Clinical Trial Site in the Seattle Area Managed Clinical Trials and Patient Care During the COVID-19 Pandemic

text: OBJECTIVES: As the COVID-19 pandemic developed in March 2020 in greater Seattle, our clinical trial site faced several ethical and clinical dilemmas. We remained open to research patients including high-risk elderly patients and adapted to changing health recommendations. METHODS: Beginning March 14, 2020 we developed an in-person evaluation for potential risk of COVID-19. Included are the first 3 weeks of screening by our physicians for potential exposure to COVID-19, common symptoms, temperature, blood oxygen saturation, and heart rate. Individuals with higher risk (n=23) were identified and managed. RESULTS: The 825 evaluations included 37 staff, 167 patients, and 152 visitors. No one needed isolation or transfer to acute care facility, staff attendance was 95%, all 33 geriatric patients continued in phase II trials, and others decreased by 5%. CONCLUSION: We share how we incorporated COVID-19 Center for Disease Control health recommendations to a clinical trial center and addition of pulse oximetry.


title: An update on canine coronaviruses: Viral evolution and pathobiology

text: Abstract The emergence of human severe acute respiratory syndrome incited renewed interest in animal coronaviruses (CoVs) as potential agents of direct and indirect zoonoses. The reinforced epidemiological surveillance on CoVs has led to the identification of new viruses, genotypes, pathotypes and host variants in animals and humans. In dogs, a CoV associated with mild enteritis, canine coronavirus (CCoV), has been known since 1970s. CoV strains with different biological and genetic properties with respect to classical CCoV strains have been identified in dogs in the last few years, leading to a full reconsideration of the CoV-induced canine diseases. The genetic evolution of dog CoVs is paradigmatic of how CoVs evolve through accumulation of point mutations, insertions or deletions in the viral genome, that led to the emergence of new genotypes (CCoV type I), biotypes (pantropic CCoV) and host variants (canine respiratory coronavirus). This paper is a review of the current literature on the recent genetic evolution of CCoV and emergence of new CoVs in the dog. The significances of the newly acquired information for the canine health status and prophylaxis programmes are also discussed.


title: Discovery of a new antiviral protein isolated Lonomia obliqua analysed by bioinformatics and real-time approaches

text: This study presents a new recombinant protein that acts as a powerful antiviral (rAVLO—recombinant Antiviral protein of Lonomia obliqua). It was able to reduce the replication by 10(6) fold for herpes virus and by 10(4) fold for rubella virus. RT-PCR of viral RNA rAVLO treated infected cells also showed similar rate of inhibition in replication. The analysis of this protein by bioinformatics suggests that this protein is globular, secreted with a signal peptide and has the ability to bind to MHC class I. It was found that there are several protein binding sites with various HLA and a prevalence of α-helices in the N-terminal region (overall classified as a α/β protein type). BLAST similarity sequence search for corresponding cDNA did not reveal a similar sequence in Genbank, suggesting that it is from a novel protein family. In this study we have observed that this recombinant protein and hemolymph has a potent antiviral action. This protein was produced in a baculovirus/Sf-9 system. Therefore, these analyses suggest that this novel polypeptide is a candidate as a broad spectrum antiviral.


title: Separation and analysis of glycyrrhizin, 18β-glycyrrhetic acid and 18α-glycyrrhetic acid in liquorice roots by means of capillary zone electrophoresis

text: Abstract Glycyrrhizin is the main active compound of Glycyrrhiza glabra root extracts; according to recent studies, glycyrrhizin and its aglycon, glycyrrhetic acid, have interesting therapeutic properties. A new capillary electrophoretic method has been developed for the separation and quantification of glycyrrhizin, β-glycyrrhetic acid and its isomer α-glycyrrhetic acid. Separation of the analytes was achieved in less than 3min on a fused silica capillary, by injecting the samples at the short end of the capillary (effective length: 8.5cm). The background electrolyte was composed of pH 10.0 carbonate buffer, methanol and ethylene glycol (80/10/10) and contained 0.4% β-cyclodextrin; indomethacin was used as the internal standard. Diode array detection was used, with quantitative assays carried out at 254nm. Linearity was found over the 5–200 and 2.5–100μgmL−1 concentration ranges for glycyrrhizin and glycyrrhetic acid, respectively. This method has been applied to the determination of the analytes in different matrices (liquorice roots and commercial confectionery products), and to the purity control of β-glycyrrhetic acid obtained from the hydrolysis of glycyrrhizin. When analysing β-glycyrrhetic acid and its epimer in roots, the samples were purified by means of a suitable solid-phase extraction (SPE) procedure with Oasis HLB cartridges, which granted good selectivity, eliminating matrix interference.


title: Streptococcus pneumoniae colonization of the nasopharynx is associated with increased severity during respiratory syncytial virus infection in young children

text: BACKGROUND AND OBJECTIVE: Respiratory syncytial virus (RSV) is the most significant cause of acute respiratory infection (ARI) in early life. RSV and other respiratory viruses are known to stimulate substantial outgrowth of potentially pathogenic bacteria in the upper airways of young children. However, the clinical significance of interactions between viruses and bacteria is currently unclear. The present study aimed to clarify the effect of viral and bacterial co‐detections on disease severity during paediatric ARI. METHODS: Nasopharyngeal aspirates from children under 2 years of age presenting with ARI to the emergency department were screened by quantitative PCR for 17 respiratory viruses and the bacterial pathogens Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. Associations between pathogen detection and clinical measures of disease severity were investigated. RESULTS: RSV was the most common virus detected, present in 29 of 58 samples from children with ARI (50%). Detection of S. pneumoniae was significantly more frequent during RSV infections compared to other respiratory viruses (adjusted effect size: 1.8, P: 0.03), and co‐detection of both pathogens was associated with higher clinical disease severity scores (adjusted effect size: 1.2, P: 0.03). CONCLUSION: Co‐detection of RSV and S. pneumoniae in the nasopharynx was associated with more severe ARI, suggesting that S. pneumoniae colonization plays a pathogenic role in young children.


Achieving A Certain Major Achievement During Uncertain Times


title: The impact of direct‐fed microbials and enzymes on the health and performance of dairy cows with emphasis on colostrum quality and serum immunoglobulin concentrations in calves

text: Thirty‐six cows were blocked by calving date and randomly assigned to one of three treatments. Cows were on treatments 3 weeks prepartum through 8 weeks post‐partum. Treatments were as follows: (i) no direct‐fed microbial (DFM) or cellulase and amylase enzymes (C), (ii) 45.4 g/day of DFM (D) or (iii) 45.4 g/day of DFM and 18.2 g/day of enzyme (DE). Total mixed ration fed and refused were measured daily to determine dry matter intake (DMI). Blood samples were taken three times weekly and analysed for β‐hydroxybutyrate, glucose and non‐esterified fatty acids. Body weight (BW) was measured weekly. Colostrum was weighed and analysed for IgA and IgG concentration. Calves were fed 4 L of colostrum within 2 hr of birth. Calf blood samples were taken at 0 and 24 hr for analysis of IgA and IgG concentrations and apparent efficiency of absorption. Milk yield was measured daily and samples collected weekly. Initial BW was different among treatments with D being lesser than C or DE treatments. Body weight, weight gain, efficiency of gain, DMI and blood parameters were unaffected. Treatment did not affect colostrum yield. Ash percentage of colostrum tended to increase with D and DE, while IgA and total solids yield decreased with D. Colostrum fat yield was decreased in D and DE. Treatments did not impact BW, serum IgA and IgG concentrations or apparent efficiency of absorption of calves. Post‐partum BW, DMI, blood parameters, milk production and composition were unaffected by treatment. However, cows on D gained more BW and tended to have greater efficiency of gain compared to those on DE, but were similar to C. Somatic cell scores were greatest for D. Results indicate that DFM and enzyme supplementation did not improve health and performance of dairy cattle during the pre‐ and post‐partum periods under conditions of this study.


title: Evidence of Increasing Diversification of Emerging SARS‐CoV‐2 Strains

text: BACKGROUND: On January 30th, 2020, an outbreak of atypical pneumonia caused by a novel Betacoronavirus (βCoV), named SARS‐CoV‐2, was declared a public health emergency of international concern by the World Health Organization. For this reason, a detailed evolutionary analysis of SARS‐CoV‐2 strains currently circulating in different geographic regions of the world was performed. METHODS: A compositional analysis as well as a Bayesian coalescent analysis of complete genome sequences of SARS‐CoV‐2 strains recently isolated in Europe, North America, South America and Asia was performed. RESULTS: The results of these studies revealed a diversification of SARS‐CoV‐2 strains in three different genetic clades. Co‐circulation of different clades in different countries, as well as different genetic lineages within different clades were observed. The time of the most recent common ancestor (tMRCA) was established to be around November 1, 2019. A mean rate of evolution of 6.57 x 10(‐4) substitutions per site per year was found. A significant migration rate per genetic lineage per year from Europe to South America was also observed. CONCLUSION: The results of these studies revealed an increasing diversification of SARS‐CoV‐2 strains. High evolutionary rates and fast population growth characterizes the population dynamics of SARS‐CoV‐2 strains. This article is protected by copyright. All rights reserved.


title: Managing public health crises: the role of models in pandemic preparedness

text: Background Given the enormity of challenges involved in pandemic preparedness, design and implementation of effective and cost‐effective public health policies is a major task that requires an integrated approach through engagement of scientific, administrative, and political communities across disciplines. There is ample evidence to suggest that modeling may be a viable approach to accomplish this task. Methods To demonstrate the importance of synergism between modelers, public health experts, and policymakers, the University of Winnipeg organized an interdisciplinary workshop on the role of models in pandemic preparedness in September 2008. The workshop provided an excellent opportunity to present outcomes of recent scientific investigations that thoroughly evaluate the merits of preventive, therapeutic, and social distancing mechanisms, where community structures, priority groups, healthcare providers, and responders to emergency situations are given specific consideration. Results This interactive workshop was clearly successful in strengthening ties between various disciplines and creating venues for modelers to effectively communicate with policymakers. The importance of modeling in pandemic planning was highlighted, and key parameters that affect policy decision‐making were identified. Core assumptions and important activities in Canadian pandemic plans at the provincial and national levels were also discussed. Conclusions There will be little time for thoughtful and rapid reflection once an influenza pandemic strikes, and therefore preparedness is an unavoidable priority. Modeling and simulations are key resources in pandemic planning to map out interdependencies and support complex decision‐making. Models are most effective in formulating strategies for managing public health crises when there are synergies between modelers, planners, and policymakers.


title: Development and application of an indirect enzyme-linked immunosorbent assay based on recombinant capsid protein for the detection of mink circovirus infection

text: BACKGROUND: Mink circovirus (MiCV) is a newly discovered pathogen associated with mink diarrhea. The prevalence and economic importance of this virus remain poorly understood, and no specific serological assay has been developed for the diagnosis of MiCV infection. RESULTS: In this study, a recombinant capsid protein antigen expressed in Escherichia coli was utilized to establish an indirect enzyme-linked immunosorbent assay (iELISA). Results revealed that the assay had no cross-reactivity with other related pathogens, and the respective sensitivity and specificity of the proposed iELISA were 92.31% and 91.67% compared with those obtained of Western blot on 138 serum samples from minks. The correlation coefficient between iELISA and Western blot was 0.838 (p > 0.05). iELISA was applied to detect MiCV antibodies in 683 clinical serum samples from different farms from the major mink industry province in China, and 21 of 24 farms with 163 of 683 (23.87%) individuals were tested positive for MiCV antibodies. The positive rates of each of the 21 flocks ranged from 2.33% to 73.68%. CONCLUSIONS: These results indicated that iELISA was a sensitive and specific method suitable for the large-scale detection of MiCV infections in mink. This study provided an effective method for the serological diagnosis and positive rate investigation of MiCV infection.


Integrated infection control strategy to minimize nosocomial infection during outbreak of COVID-19 among ED healthcare workers


title: A functional nuclear localization sequence in the VP1 capsid protein of coxsackievirus B3

text: Abstract The capsid proteins of some RNA viruses can translocate to the nucleus and interfere with cellular phenotypes. In this study we found that the VP1 capsid protein of coxsackievirus B3 (CVB3) was dominantly localized in the nucleus of the cells transfected with VP1-expressing plasmid. The VP1 nuclear localization also occurred in the cells infected with CVB3. Truncation analysis indicated that the VP1 nuclear localization sequence located near the C-terminal. The substitution of His220 with threonine completely abolished its translocation. The VP1 proteins of other CVB types might have the nuclear localization potential because this region was highly conserved. Moreover, the VP1 nuclear localization induced cell cycle deregulation, including a prolonged S phase and shortened G2-M phase. Besides these findings, we also found a domain between Ala72 and Phe106 that caused the VP1 truncates dotted distributed in the cytoplasm. Our results suggest a new pathogenic mechanism of CVB.


title: Acute Limb Ischemia Due to Arterial Thrombosis Associated With Coronavirus Disease 2019

text: OBJECTIVES: To describe a case of acute limb ischemia caused by arterial thrombosis due to coronavirus disease 2019. DESIGN: Clinical observation of a patient. SETTING: Academic medical center. PATIENT: A 59-year-old female with history of hypertension, hyperlipidemia, and prior smoking. INTERVENTION: Clinical observation and data extraction from electronic medical records. MEASUREMENTS AND MAIN RESULTS: We report a case of peripheral arterial thrombosis associated with coronavirus disease 2019, resulting in acute limb ischemia of the right lower extremity. This event was heralded by a sudden and significant elevation in d-dimer levels. At the time of surgery, a long, gelatinous clot was retrieved from the right popliteal artery. Perioperatively, she continued to have absent pedal Doppler signals and after multiple embolectomy attempts, required distal arterial cut down with removal of additional thrombi and resultant improvement of distal arterial flow. CONCLUSIONS: This case demonstrates the importance of regularly checking d-dimer levels and vigilant monitoring for arterial thrombotic events, as they can rapidly become catastrophic.


title: Isolation Facilities for Highly Infectious Diseases in Europe – A Cross-Sectional Analysis in 16 Countries

text: BACKGROUND: Highly Infectious Diseases (HIDs) are (i) easily transmissible form person to person; (ii) cause a life-threatening illness with no or few treatment options; and (iii) pose a threat for both personnel and the public. Hence, even suspected HID cases should be managed in specialised facilities minimizing infection risks but allowing state-of-the-art critical care. Consensus statements on the operational management of isolation facilities have been published recently. The study presented was set up to compare the operational management, resources, and technical equipment among European isolation facilities. Due to differences in geography, population density, and national response plans it was hypothesized that adherence to recommendations will vary. METHODS AND FINDINGS: Until mid of 2010 the European Network for Highly Infectious Diseases conducted a cross-sectional analysis of isolation facilities in Europe, recruiting 48 isolation facilities in 16 countries. Three checklists were disseminated, assessing 44 items and 148 specific questions. The median feedback rate for specific questions was 97.9% (n = 47/48) (range: n = 7/48 (14.6%) to n = 48/48 (100%). Although all facilities enrolled were nominated specialised facilities' serving countries or regions, their design, equipment and personnel management varied. Eighteen facilities fulfilled the definition of a High Level Isolation Unit'. In contrast, 24 facilities could not operate independently from their co-located hospital, and five could not ensure access to equipment essential for infection control. Data presented are not representative for the EU in general, as only 16/27 (59.3%) of all Member States agreed to participate. Another limitation of this study is the time elapsed between data collection and publication; e.g. in Germany one additional facility opened in the meantime. CONCLUSION: There are disparities both within and between European countries regarding the design and equipment of isolation facilities. With regard to the International Health Regulations, terminology, capacities and equipment should be standardised.


title: Posterior oropharyngeal saliva for the detection of SARS-CoV-2

text: BACKGROUND: The coronavirus disease-2019 (COVID-19) pandemic has put tremendous pressure on the healthcare system worldwide. Diagnostic testing remained one of the limiting factors for early identification and isolation of infected patients. This study aimed to evaluate posterior oropharyngeal saliva (POPS) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection among patients with confirmed or suspected COVID-19. METHODS: The laboratory information system was searched retrospectively for all respiratory specimens and POPS requested for SARS-CoV-2 RNA detection between Feb 1, 2020 and Apr 15, 2020. The agreement and diagnostic performance of POPS against NPsp were evaluated. RESULTS: A total of 13772 specimens were identified during the study period, including 2130 POPS and 8438 NPsp. Two hundred and twenty-nine same-day POPS-NPsp paired were identified with POPS and NPsp positivity of 61.5% (95% CI [55.1–67.6%]) and 53.3% (95% CI [46.8–59.6%]). The overall, negative and positive percent agreement were 76.0% (95% CI [70.2–80.9%]), 65.4% (95% CI [55.5–74.2%]), 85.2% (95% CI [77.4–90.8%]). Better positive percent agreement was observed in POPS-NPsp obtained within seven days (96.6%, 95% CI [87.3–99.4%]) compared with after seven days of symptom onset (75.0%, 95% CI [61.4–85.2%)). Among the 104 positive pairs, the mean difference in Cp value was 0.26 (range: 12.63 to -14.74), with an overall higher Cp value in NPsp (Pearson coefficient 0.579). No significant temporal variation was noted between the two specimen types. CONCLUSIONS: POPS is an acceptable alternative specimen to nasopharyngeal specimen for the detection of SARS-CoV-2.


title: Anesthetic Considerations During Heart Transplantation using Donation after Circulatory Death

text: Worldwide, the majority of heart transplant organs are from donation after brain death (DBD). However, the shortage of suitable donors places severe limitations on this route. One option to increase the donor pool is to use organs from donation after circulatory death (DCD). Transplant centers for solid organs have been using DCD organs for years. At this time, 40% of solid organ transplantation in the UK use organs from DCD. Use of DCD for solid organ transplants in Canada is also rising. Recently, there has been interest in using DCD organs for heart transplantation. We will discuss our experience of 4 heart transplants with organs from DCD donors after normothermic regional perfusion (NRP). Our first heart transplant using a DCD organ was in January 2020, and the fourth was in March 2020, just before the COVID-19 pandemic. Our protocol using NRP allows us to evaluate the donor heart adequately to confidently determine organ acceptance. The co-location of the donor and the recipient in neighboring ORs limits ischemic times. Avoidance of an expensive ex-vivo organ perfusion machine is an additional benefit for programs that may not have the resources required to purchase and maintain the machine. Some hospitals may not have the resources and space to be able to co-locate both the donor and recipient. Use of cold storage may be an option to transport the procured organ, similar to DBD organs. We hope that this technique of NRP in DCD donors can help further increase the donor pool for heart transplantation in the US.


title: Covid‐19: countermeasure for N95 mask‐induced pressure sore

text: As known to all, World Health Organization has declared on March 11th, 2020 that Coronavirus (Covid-19) epidemic could be characterized as a pandemic, which proposed a big challenge for healthcare works worldwide, especially doctors and nurses. The strong infectiousness of SARS-CoV-2 forces medical personnel to do good and needful safeguard against virus.


title: Rapid Detection, Complete Genome Sequencing, and Phylogenetic Analysis of Porcine Deltacoronavirus

text: In February 2014, porcine deltacoronavirus (PDCoV) was identified in the United States. We developed a PDCoV real-time reverse transcription PCR that identified PDCoV in 30% of samples tested. Four additional PDCoV genomes from the United States were sequenced; these had ≈99%–100% nt similarity to the other US PDCoV strains.


title: ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation

text: Malnutrition affects up to one billion people in the world and is a major cause of mortality(1,2). In many cases, malnutrition is associated with diarrhoea and intestinal inflammation, further contributing to morbidity and death(2). The mechanisms by which unbalanced dietary nutrients affect intestinal homeostasis are largely unknown. Here we report that deficiency in murine angiotensin I converting enzyme (peptidyl-dipeptidase A) 2 (Ace2), which encodes a key regulatory enzyme of the renin-angiotensin system (RAS), results in highly increased susceptibility to intestinal inflammation induced by epithelial damage. The RAS is known to be involved in acute lung failure(3), cardiovascular functions(4) and SARS infections(5). Mechanistically, ACE2 has a RAS-independent function, regulating intestinal amino acid homeostasis, expression of antimicrobial peptides, and the ecology of the gut microbiome. Transplantation of the altered microbiota from Ace2 mutant mice into germ-free wild-type hosts was able to transmit the increased propensity to develop severe colitis. ACE2-dependent changes in epithelial immunity and the gut microbiota can be directly regulated by the dietary amino acid tryptophan. Our results identify ACE2 as a key regulator of dietary amino acid homeostasis, innate immunity, gut microbial ecology, and transmissible susceptibility to colitis. These results provide a molecular explanation for how amino acid malnutrition can cause intestinal inflammation and diarrhoea. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nature11228) contains supplementary material, which is available to authorized users.


title: Factors associated with death outcome in patients with severe coronavirus disease-19 (COVID-19): a case-control study

text: Rationale: Up to date, the exploration of clinical features in severe COVID-19 patients were mostly from the same center in Wuhan, China. The clinical data in other centers is limited. This study aims to explore the feasible parameters which could be used in clinical practice to predict the prognosis in hospitalized patients with severe coronavirus disease-19 (COVID-19). Methods: In this case-control study, patients with severe COVID-19 in this newly established isolation center on admission between 27 January 2020 to 19 March 2020 were divided to discharge group and death event group. Clinical information was collected and analyzed for the following objectives: 1. Comparisons of basic characteristics between two groups; 2. Risk factors for death on admission using logistic regression; 3. Dynamic changes of radiographic and laboratory parameters between two groups in the course. Results: 124 patients with severe COVID-19 on admission were included and divided into discharge group (n=35) and death event group (n=89). Sex, SpO2, breath rate, diastolic pressure, neutrophil, lymphocyte, C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), and D-dimer were significantly correlated with death events identified using bivariate logistic regression. Further multivariate logistic regression demonstrated a significant model fitting with C-index of 0.845 (p<0.001), in which SpO2≤89%, lymphocyte≤0.64×10(9)/L, CRP>77.35mg/L, PCT>0.20μg/L, and LDH>481U/L were the independent risk factors with the ORs of 2.959, 4.015, 2.852, 3.554, and 3.185, respectively (p<0.04). In the course, persistently lower lymphocyte with higher levels of CRP, PCT, IL-6, neutrophil, LDH, D-dimer, cardiac troponin I (cTnI), brain natriuretic peptide (BNP), and increased CD4+/CD8+ T-lymphocyte ratio and were observed in death events group, while these parameters stayed stable or improved in discharge group. Conclusions: On admission, the levels of SpO2, lymphocyte, CRP, PCT, and LDH could predict the prognosis of severe COVID-19 patients. Systematic inflammation with induced cardiac dysfunction was likely a primary reason for death events in severe COVID-19 except for acute respiratory distress syndrome.


Notes and Comments on “Proposed Approach for Re-using Surgical Masks in COVID-19 Pandemic”


title: Improving estimates of the basic reproductive ratio: Using both the mean and the dispersal of transition times

text: Abstract In both within-host and epidemiological models of pathogen dynamics, the basic reproductive ratio, R 0 , is a powerful tool for gauging the risk associated with an emerging pathogen, or for estimating the magnitude of required control measures. Techniques for estimating R 0 , either from incidence data or in-host clinical measures, often rely on estimates of mean transition times, that is, the mean time before recovery, death or quarantine occurs. In many cases, however, either data or intuition may provide additional information about the dispersal of these transition times about the mean, even if the precise form of the underlying probability distribution remains unknown. For example, we may know that recovery typically occurs within a few days of the mean recovery time. In this paper we elucidate common situations in which R 0 is sensitive to the dispersal of transition times about their respective means. We then provide simple correction factors that may be applied to improve estimates of R 0 when not only the mean but also the standard deviation of transition times out of the infectious state can be estimated.


title: Proteomic analysis of chicken embryonic trachea and kidney tissues after infection in ovo by avian infectious bronchitis coronavirus

text: BACKGROUND: Avian infectious bronchitis (IB) is one of the most serious diseases of economic importance in chickens; it is caused by the avian infectious coronavirus (IBV). Information remains limited about the comparative protein expression profiles of chicken embryonic tissues in response to IBV infection in ovo. In this study, we analyzed the changes of protein expression in trachea and kidney tissues from chicken embryos, following IBV infection in ovo, using two-dimensional gel electrophoresis (2-DE) coupled with matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF-TOF MS). RESULTS: 17 differentially expressed proteins from tracheal tissues and 19 differentially expressed proteins from kidney tissues were identified. These proteins mostly related to the cytoskeleton, binding of calcium ions, the stress response, anti-oxidative, and macromolecular metabolism. Some of these altered proteins were confirmed further at the mRNA level using real-time RT-PCR. Moreover, western blotting analysis further confirmed the changes of annexin A5 and HSPB1 during IBV infection. CONCLUSIONS: To the best of our knowledge, we have performed the first analysis of the proteomic changes in chicken embryonic trachea and kidney tissues during IBV infection in ovo. The data obtained should facilitate a better understanding of the pathogenesis of IBV infection.


title: A host-restricted viral vector for antigen-specific immunization against Lyme disease pathogen

text: Newcastle disease virus (NDV) is an avian virus that is attenuated in primates and is a potential vaccine vector for human use. We evaluated NDV as a vector for expressing selected antigens of the Lyme disease pathogen Borrelia burgdorferi. A series of recombinant NDVs were generated that expressed intracellular or extracellular forms of two Borrelia burgdorferi antigens: namely, the basic membrane protein A (BmpA) and the outer surface protein C (OspC). Expression of the intracellular and extracellular forms of these antigens was confirmed in cultured chicken cells. C3H or Balb/C mice that were immunized intranasally with the NDV vectors mounted vigorous serum antibody responses against the NDV vector, but failed to mount a robust response against either the intracellular or extracellular forms of BmpA or OspC. In contrast, a single immunization of hamsters with the NDV vectors via the intranasal, intramuscular, or intraperitoneal route resulted in rapid and rigorous antibody responses against the intracellular or extracellular forms of BmpA and OspC. When groups of hamsters were separately inoculated with various NDV vectors and challenged with B. burgdorferi (10(8) cells/animal), immunization with vector expressing either intracellular or extracellular BmpA was associated with a significant reduction of the pathogen load in the joints. Taken together, our studies highlighted the importance of NDV as vaccine vector that can be used for simple yet effective immunization of hosts against bacterial infections including Lyme disease.


title: D471G Mutation in LCMV-NP Affects its Ability to Self-associate and Results in a Dominant Negative Effect in Viral RNA Synthesis

text: Arenaviruses merit significant interest because several family members are etiological agents of severe hemorrhagic fevers, representing a major burden to public health. Currently, there are no FDA-licensed vaccines against arenaviruses and the only available antiviral therapy is limited to the use of ribavirin that is partially effective. Arenavirus nucleoprotein (NP) is found associated with the genomic RNA forming the viral ribonucleoproteins (vRNPs) that together with the polymerase (L) direct viral replication and transcription. Virion formation requires the recruitment of vRNPs into budding sites, a process in which the arenavirus matrix-like protein (Z) plays a major role. Therefore, proper NP-NP and NP-Z interactions are required for the generation of infectious progeny. In this work we demonstrate the role of the amino acid residue D471 in the self-association of lymphocytic choriomeningitis virus nucleoprotein (LCMV-NP). Amino acid substitutions at this position abrogate NP oligomerization, affecting its ability to mediate replication and transcription of a minigenome reporter plasmid. However, its ability to interact with the Z protein, counteract the cellular interferon response and bind to dsRNA analogs was retained. Additionally, we also document the dominant negative effect of D471G mutation on viral infection, suggesting that NP self-association is an excellent target for the development of new antivirals against arenaviruses.


title: Wildlife cancer: a conservation perspective

text: Until recently, cancer in wildlife was not considered to be a conservation concern. However, with the identification of Tasmanian devil facial tumour disease, sea turtle fibropapillomatosis and sea lion genital carcinoma, it has become apparent that neoplasia can be highly prevalent and have considerable effects on some species. It is also clear that anthropogenic activities contribute to the development of neoplasia in wildlife species, such as beluga whales and bottom-dwelling fish, making them sensitive sentinels of disturbed environments.


title: Insight into capacity planning for cardiac catheterization services: Policy lessons learned from “Looking in the Mirror” over a decade

text: Abstract Background Cardiac catheterization (CATH) is key in the diagnosis and management of coronary artery disease. Increasing demand coupled with limited resources in a publicly funded system (e.g. Ontario, the largest province in Canada) resulted in a waitlist for this procedure. Our province has recommended maximum wait times (RMWT) for patients referred to CATH. The purpose of this study is to describe our experience over the past decade in attempting to meet RMWTs for patients needing CATH at our centre, and to discuss issues concerning capacity planning in providing timely service. Methods We measured the proportion of patients undergoing a procedure within the RWMT, and calculated both the mean number of patients and mean length of time on the wait list for each year over a decade for those referred to CATH using prospectively collected registry data. We identified factors that increased referrals or improved capacity. Wait time was compared to community standard RMWTs in order to establish if and how RMWTs were achieved. Results Despite a number of systematic and capacity improvements, RMWTs were not achieved until after the addition of a 4th laboratory. Interpretation Improving access to CATH in our centre was reactive to the increasing need of the community rather than based on anticipation of need and continuity of service within RMWTs. Registry data can help monitor key indicators (e.g. RMWT). Prudent use of this information should help policy makers with future expansion in our region.


title: The novel H1N1 Influenza A global airline transmission and early warning without travel containments

text: A novel influenza A (H1N1) has been spreading worldwide. Early studies implied that international air travels might be key cause of a severe potential pandemic without appropriate containments. In this study, early outbreaks in Mexico and some cities of United States were used to estimate the preliminary epidemic parameters by applying adjusted SEIR epidemiological model, indicating transmissibility infectivity of the virus. According to the findings, a new spatial allocation model totally based on the real-time airline data was established to assess the potential spreading of H1N1 from Mexico to the world. Our estimates find the basic reproductive number R0 of H1N1 is around 3.4, and the effective reproductive number fall sharply by effective containment strategies. The finding also implies Spain, Canada, France, Panama, Peru are the most possible country to be involved in severe endemic H1N1 spreading.


title: Chicken GRIFIN: Structural characterization in crystals and in solution

text: Abstract Despite its natural abundance in lenses of vertebrates the physiological function(s) of the galectin-related inter-fiber protein (GRIFIN) is (are) still unclear. The same holds true for the significance of the unique interspecies (fish/birds vs mammals) variability in the capacity to bind lactose. In solution, ultracentrifugation and small angle X-ray scattering (at concentrations up to 9 mg/mL) characterize the protein as compact and stable homodimer without evidence for aggregation. The crystal structure of chicken (C-)GRIFIN at seven pH values from 4.2 to 8.5 is reported, revealing compelling stability. Binding of lactose despite the Arg71Val deviation from the sequence signature of galectins matched the otherwise canonical contact pattern with thermodynamics of an enthalpically driven process. Upon lactose accommodation, the side chain of Arg50 is shifted for hydrogen bonding to the 3-hydroxyl of glucose. No evidence for a further ligand-dependent structural alteration was obtained in solution by measuring hydrogen/deuterium exchange mass spectrometrically in peptic fingerprints. The introduction of the Asn48Lys mutation, characteristic for mammalian GRIFINs that have lost lectin activity, lets labeled C-GRIFIN maintain capacity to stain tissue sections. Binding is no longer inhibitable by lactose, as seen for the wild-type protein. These results establish the basis for detailed structure-activity considerations and are a step to complete the structural description of all seven members of the galectin network in chicken.


title: Lack of Handwashing Access: A Widespread Deficiency in the Age of COVID-19

text: [Figure: see text]


title: Enteric involvement of severe acute respiratory syndrome-associated coronavirus infection 1 1 The authors thank Man-yee Yung, Sara Fung, Dr. Bonnie Kwan, and Dr. Thomas Li for their help in retrieving patient information.

text: Abstract Background & Aims : Severe acute respiratory syndrome (SARS) is a recently emerged infection from a novel coronavirus (CoV). Apart from fever and respiratory complications, gastrointestinal symptoms are frequently observed in patients with SARS but the significance remains undetermined. Herein, we describe the clinical, pathologic, and virologic features of the intestinal involvement of this new viral infection. Methods : A retrospective analysis of the gastrointestinal symptoms and other clinical parameters of the first 138 patients with confirmed SARS admitted for a major outbreak in Hong Kong in March 2003 was performed. Intestinal specimens were obtained by colonoscopy or postmortem examination to detect the presence of coronavirus by electron microscopy, virus culture, and reverse-transcription polymerase chain reaction. Results : Among these 138 patients with SARS, 28 (20.3%) presented with watery diarrhea and up to 38.4% of patients had symptoms of diarrhea during the course of illness. Diarrhea was more frequently observed during the first week of illness. The mean number of days with diarrhea was 3.7 ± 2.7, and most diarrhea was self-limiting. Intestinal biopsy specimens obtained by colonoscopy or autopsy showed minimal architectural disruption but the presence of active viral replication within both the small and large intestine. Coronavirus was also isolated by culture from these specimens, and SARS-CoV RNA can be detected in the stool of patients for more than 10 weeks after symptom onset. Conclusions : Diarrhea is a common presenting symptom of SARS. The intestinal tropism of the SARS-CoV has major implications on clinical presentation and viral transmission.


title: Polymorphism of SARS-CoV Genomes

text: Abstract In this work, severe acute respiratory syndrome associated coronavirus (SARS-CoV) genome BJ202 (AY864806) was completely sequenced. The genome was directly accessed from the stool sample of a patient in Beijing. Comparative genomics methods were used to analyze the sequence variations of 116 SARS-CoV genomes (including BJ202) available in the NCBI Gen-Bank. With the genome sequence of GZ02 as the reference, there were 41 polymorphic sites identified in BJ202 and a total of 278 polymorphic sites present in at least two of the 116 genomes. The distribution of the polymorphic sites was biased over the whole genome. Nearly half of the variations (50.4%, 140/278) clustered in the one third of the whole genome at the 3′ end (19.0 kb-29.7 kb). Regions encoding Orf10–11, Orf3/4, E, M and S protein had the highest mutation rates. A total of 15 PCR products (about 6.0 kb of the genome) including 11 fragments containing 12 known polymorphic sites and 4 fragments without identified polymorphic sites were cloned and sequenced. Results showed that 3 unique polymorphic sites of BJ202 (positions 13 804, 15 031 and 20 792) along with 3 other polymorphic sites (26 428, 26 477 and 27 243) all contained 2 kinds of nucleotides. It is interesting to find that position 18379 which has not been identified to be polymorphic in any of the other 115 published SARS-CoV genomes is actually a polymorphic site. The nucleotide composition of this site is A (8) to G (6). Among 116 SARS-CoV genomes, 18 types of deletions and 2 insertions were identified. Most of them were related to a 300 bp region (27 700–28 000) which encodes parts of the putative ORF9 and ORF10–11. A phylogenetic tree illustrating the divergence of whole BJ202 genome from 115 other completely sequenced SARS-CoVs was also constructed. BJ202 was phylogeneticly closer to BJ01 and LLJ-2004.


title: Functional Diversity of Chemokines and Chemokine Receptors in Response to Viral Infection of the Central Nervous System

text: Encounters with neurotropic viruses result in varied outcomes ranging from encephalitis, paralytic poliomyelitis or other serious consequences to relatively benign infection. One of the principal factors that control the outcome of infection is the localized tissue response and subsequent immune response directed against the invading toxic agent. It is the role of the immune system to contain and control the spread of virus infection in the central nervous system (CNS), and paradoxically, this response may also be pathologic. Chemokines are potent proinflammatory molecules whose expression within virally infected tissues is often associated with protection and/or pathology which correlates with migration and accumulation of immune cells. Indeed, studies with a neurotropic murine coronavirus, mouse hepatitis virus (MHV), have provided important insight into the functional roles of chemokines and chemokine receptors in participating in various aspects of host defense as well as disease development within the CNS. This chapter will highlight recent discoveries that have provided insight into the diverse biologic roles of chemokines and their receptors in coordinating immune responses following viral infection of the CNS.


Editorial overview: Emerging viruses: interspecies transmission


An Invited Commentary on “Impact of the Coronavirus (COVID-19) pandemic on surgical practice-part 1”. Impact of the Coronavirus (COVID-19) pandemic on surgical practice: Time to embrace Telehealth in Surgery


title: 9 Targeted Adenoviral Vectors I Transductional Targeting

text: Abstract Human adenovirus (Ad) has been used extensively to develop gene transfer vectors for vaccine and gene therapy applications. A major factor limiting the efficacy of the current generation of Ad vectors is their inability to accomplish specific gene delivery to the cells of interest. Transductional targeting strategies seek to redirect virus binding to the appropriate cellular receptor to increase infection efficiency in selected cell types to achieve therapeutic intervention. These efforts mainly focused on incorporating targeting ligands by means of chemical conjugation or genetic modification of Ad capsid proteins and using bispecific adapter molecules to mediate virus recognition of target cells. This review summarizes current progress in Ad tropism modification maneuvers that embody genetic capsid modification and adapter-based approaches that have encouraging implications for further development of advanced vectors suitable for clinical translation.


Dengue and Relative Bradycardia


title: SARS and Common Viral Infections

text: In California, molecular testing was useful in decreasing suspicion for severe acute respiratory syndrome (SARS), by detecting common respiratory pathogens (influenza A/B, human metapneumovirus, picornavirus, Mycoplasma pneumoniae, Chlamydia spp., parainfluenza virus, respiratory syncytial virus, and adenovirus) in 23 (45%) of 51 patients with suspected SARS and 9 (47%) of 19 patients with probable SARS.


title: A Patient with Asymptomatic Severe Acute Respiratory Syndrome (SARS) and Antigenemia from the 2003–2004 Community Outbreak of SARS in Guangzhou, China

text: An asymptomatic case of severe acute respiratory syndrome (SARS) occurred early in 2004, during a community outbreak of SARS in Guangzhou, China. This was the first time that a case of asymptomatic SARS was noted in an individual with antigenemia and seroconversion. The asymptomatic case patient and the second index case patient with SARS in the 2003–2004 outbreak both worked in the same restaurant, where they served palm civets, which were found to carry SARS-associated coronaviruses. Epidemiological information and laboratory findings suggested that the findings for the patient with asymptomatic infection, together with the findings from previously reported serological analyses of handlers of wild animals and the 4 index case patients from the 2004 community outbreak, reflected a likely intermediate phase of animal-to-human transmission of infection, rather than a case of human-to-human transmission. This intermediate phase may be a critical stage for virus evolution and disease prevention.


title: Tick-Borne Encephalitis Virus Replication, Intracellular Trafficking, and Pathogenicity in Human Intestinal Caco-2 Cell Monolayers

text: Tick-borne encephalitis virus (TBEV) is one of the most important vector-borne viruses in Europe and Asia. Its transmission mainly occurs by the bite of an infected tick. However, consuming milk products from infected livestock animals caused TBEV cases. To better understand TBEV transmission via the alimentary route, we studied viral infection of human intestinal epithelial cells. Caco-2 cells were used to investigate pathological effects of TBEV infection. TBEV-infected Caco-2 monolayers showed morphological changes including cytoskeleton rearrangements and cytoplasmic vacuolization. Ultrastructural analysis revealed dilatation of the rough endoplasmic reticulum and further enlargement to TBEV containing caverns. Caco-2 monolayers maintained an intact epithelial barrier with stable transepithelial electrical resistance (TER) during early stage of infection. Concomitantly, viruses were detected in the basolateral medium, implying a transcytosis pathway. When Caco-2 cells were pre-treated with inhibitors of cellular pathways of endocytosis TBEV cell entry was efficiently blocked, suggesting that actin filaments (Cytochalasin) and microtubules (Nocodazole) are important for PI3K-dependent (LY294002) virus endocytosis. Moreover, experimental fluid uptake assay showed increased intracellular accumulation of FITC-dextran containing vesicles. Immunofluorescence microscopy revealed co-localization of TBEV with early endosome antigen-1 (EEA1) as well as with sorting nexin-5 (SNX5), pointing to macropinocytosis as trafficking mechanism. In the late phase of infection, further evidence was found for translocation of virus via the paracellular pathway. Five days after infection TER was slightly decreased. Epithelial barrier integrity was impaired due to increased epithelial apoptosis, leading to passive viral translocation. These findings illuminate pathomechanisms in TBEV infection of human intestinal epithelial cells and viral transmission via the alimentary route.


title: Nucleocapsid protein of porcine reproductive and respiratory syndrome virus antagonizes the antiviral activity of TRIM25 by interfering with TRIM25-mediated RIG-I ubiquitination

text: Abstract Porcine reproductive and respiratory syndrome (PRRS) is caused by PRRS virus (PRRSV), and is characterized by respiratory diseases in piglet and reproductive disorders in sow. Identification of sustainable and effective measures to mitigate PRRSV transmission is a pressing problem. The nucleocapsid (N) protein of PRRSV plays a crucial role in inhibiting host innate immunity during PRRSV infection. In the current study, a new host-restricted factor, tripartite motif protein 25 (TRIM25), was identified as an inhibitor of PRRSV replication. Co-immunoprecipitation assay indicated that the PRRSV N protein interferes with TRIM25–RIG-I interactions by competitively interacting with TRIM25. Furthermore, N protein inhibits the expression of TRIM25 and TRIM25-mediated RIG-I ubiquitination to suppress interferon β production. Furthermore, with increasing TRIM25 expression, the inhibitory effect of N protein on the ubiquitination of RIG-I diminished. These results indicate for the first time that TRIM25 inhibits PRRSV replication and that the N protein antagonizes the antiviral activity by interfering with TRIM25-mediated RIG-I ubiquitination. This not only provides a theoretical basis for the development of drugs to control PRRSV replication, but also better explains the mechanism through which the PRRSV N protein inhibits innate immune responses of the host.


Una herramienta para apoyar el trabajo de los equipos quirúrgicos y afrontar el Covid 19


title: Systematic Review of Important Viral Diseases in Africa in Light of the ‘One Health’ Concept

text: Emerging and re-emerging viral diseases are of great public health concern. The recent emergence of Severe Acute Respiratory Syndrome (SARS) related coronavirus (SARS-CoV-2) in December 2019 in China, which causes COVID-19 disease in humans, and its current spread to several countries, leading to the first pandemic in history to be caused by a coronavirus, highlights the significance of zoonotic viral diseases. Rift Valley fever, rabies, West Nile, chikungunya, dengue, yellow fever, Crimean-Congo hemorrhagic fever, Ebola, and influenza viruses among many other viruses have been reported from different African countries. The paucity of information, lack of knowledge, limited resources, and climate change, coupled with cultural traditions make the African continent a hotspot for vector-borne and zoonotic viral diseases, which may spread globally. Currently, there is no information available on the status of virus diseases in Africa. This systematic review highlights the available information about viral diseases, including zoonotic and vector-borne diseases, reported in Africa. The findings will help us understand the trend of emerging and re-emerging virus diseases within the African continent. The findings recommend active surveillance of viral diseases and strict implementation of One Health measures in Africa to improve human public health and reduce the possibility of potential pandemics due to zoonotic viruses.


title: Assessing the evolutionary persistence of ecological relationships: a review and preview

text: Species interactions, such as pollination, parasitism and predation, form the basis of functioning ecosystems. The origins and resilience of such interactions therefore merit attention. However, fossils only occasionally document ancient interactions, and phylogenetic methods are blind to recent interactions. Is there some other way to track shared species experiences? “Comparative demography” examines when pairs of species jointly thrived or declined. By forging links between ecology, epidemiology, and evolutionary biology, this method sheds light on biological adaptation, species resilience, and ecosystem health. Here, we describe how this method works, discuss examples, and suggest future directions in hopes of inspiring interest, imitators, and critics.


title: Effect of Inapparent Murine Hepatitis Virus Infections on Macrophages and Host Resistance

text: Inapparent infections of mice with murine hepatitis virus (MHV) altered host resistance to experimental infection with a second virus, encephalomyocarditis virus (EMC), reduced the protective effects of exogeneously administered interferon against EMC infections, and it altered macrophage ectoenzyme phenotypes in two macrophage populations. Resident peritoneal macrophages from mice experimentally infected with one of two strains of MHV also demonstrated altered ectoenzyme phenotypes. These data demonstrate that inapparent infections with MHV alter several host resistance and macrophage parameters and directly demonstrate that effects of inapparent MHV infection on macrophage parameters can be reproduced experimentally.


title: Localization of an RNA-binding domain in the nucleocapsid protein of the coronavirus mouse hepatitis virus

text: The interaction between the nucleocapsid (N) protein of mouse hepatitis virus (MHV) and RNA was studied in an effort to define portions of the N molecule that participate in binding to RNA. N mRNAs transcribed from SP6 and T7 vectors were translated in a rabbit reticulocyte lysate. Analysis of synthesized N protein in a nondenaturing gel system showed that it bound in vitro to an endogenous RNA in the reticulocyte lysate but not to its own mRNA. A set of deletion mutants was constructed in order to localize the RNA-binding activity of the N protein. It was found that removal of as much as 135 amino-terminal or 57 carboxy-terminal amino acids from the molecule had little or no effect on RNA binding. Moreover, deletion mutants lacking both termini still retained RNA-binding ability. By contrast, internal deletions or truncations extending beyond these two limits effectively abolished RNA binding by N protein. Thus, the RNA-binding region of N has been mapped to the second (central) of the three structural domains of the molecule.


title: Chapter 3 Targeting Proteasomal Degradation of Soluble, Misfolded Proteins Ubi Major…

text: Abstract This chapter deals with small molecule modulators of the ubiquitin–proteasome system (UPS). They are designed to restore its impaired capacity to dispose of soluble, dysfunctional protein copies, and to fight its pathological impairment in proteinopathies in general and in tauopathies in particular. Two specific molecular targets belonging to the U-box E3 ligase family (C-terminus of Hsc70 interacting protein, CHIP) and to the proteasome-associated cysteine protease DUB family (USP14) are selected for their putative role against NDDs and tauopathies. The limited available structural information for the two targets, and for their interactions with members of UPS-driven protein complexes, is described. A small number of known modulators for each target (or even for structurally related targets, possibly to provide translatable examples) are portrayed in terms of their biological profile, and of their development potential as disease-modifying drugs against NDDs.


title: Managing Urology Consultations during COVID-19 Pandemic: Application of a Structured Care Pathway

text: Abstract Objectives To describe and evaluate a risk-stratified triage pathway for inpatient urology consultations during the SARS-CoV-2 (COVID-19) pandemic. This pathway seeks to outline a urology patient care strategy that reduces the transmission risk to both healthcare providers and patients, reduces the healthcare burden, and maintains appropriate patient care. Methods Consultations to the urology service during a three-week period (March 16 to April 2, 2020) were triaged and managed via one of three pathways: Standard, Telemedicine, or High-Risk. Standard consults were in-person consults with non- COVID-19 patients, High-Risk consults were in-person consults with COVID-19 positive/suspected patients, and Telemedicine consults were telephonic consults for low-acuity urologic issues in either group of patients. Patient demographics, consultation parameters and consultation outcomes were compared to consultations from the month of March 2019. Categorical variables were compared using Chi-square test and continuous variables using Mann-Whitney U test. A p-value <0.05 was considered significant. Results Between March 16 and April 2, 2020, 53 inpatient consultations were performed. By following our triage pathway, a total of 19/53 consultations (35.8%) were performed via Telemedicine with no in-person exposure, 10/53 consultations (18.9%) were High-Risk, in which we strictly controlled the urology team member in-person contact, and the remainder, 24/53 consultations (45.2%), were performed as Standard in-person encounters. COVID-19 associated consultations represented 18/53 (34.0%) of all consultations during this period, and of these, 8/18 (44.4%) were managed successfully via Telemedicine alone. No team member developed COVID-19 infection. Conclusions During the COVID-19 pandemic, most urology consultations can be managed in a patient and physician safety-conscious manner, by implementing a novel triage pathway.


title: Efficacy of intranasal and spray delivery of adjuvanted live vaccine against infectious bronchitis virus in experimentally infected poultry

text: Abstract Live vaccines are widely used in the avian industry. Such vaccines can be either injected or delivered on animal mucosa and are usually not adjuvanted. In this study we show that live vaccines efficacy can be improved by formulation with adjuvants in a model of mucosal delivery of live infectious bronchitis vaccine in chicken. Three adjuvant technologies have been tested using intranasal and spray delivery methods to poultry. Those technologies are water in oil in water emulsion, nanoparticles and polymer adjuvants. Intranasal delivery of polymer and nanoparticles adjuvanted live vaccines improved significantly the antibody titer and protection to challenge observed compared to a commercial non-adjuvanted reference. Moreover, spray delivery of the polymer adjuvanted vaccine showed a significantly higher protection compared to the non-adjuvanted reference. Our data demonstrates that the use of MontanideTM adjuvants in the formulation of live poultry vaccines for mucosal delivery can confer to vaccinated animals a significantly improved protection against pathogens.


title: Pneumonia and Other Respiratory Infections

text: Pneumonia is a leading killer of children in developing countries and results in significant morbidity worldwide. This article reviews the management of pneumonia and its complications from the perspective of both developed and resource-poor settings. In addition, evidence-based management of other respiratory infections, including tuberculosis, is discussed. Finally, the management of common complications of pneumonia is reviewed.


Improving staff safety during tracheostomy in COVID‐19 patients


title: Infections à Bocavirus humain

text: Résumé Le bocavirus humain (HboV) a été récemment cloné lors d’un criblage systématique de prélèvements nasopharyngés d’enfants hospitalisés pour infections respiratoires. Ce virus, du genre bocavirus, de la famille des Parvoviridae, a été détecté par son ADN, lors de différentes études, dans environ 5 % des prélèvements nasopharyngés. Il serait responsable d’infections respiratoires hautes et basses chez les jeunes enfant de moins de cinq ans avec un pic hivernal. Son rôle pathogène dans ces infections reste encore à déterminer, compte tenu d’un taux élevé de co-infections virales. Des études supplémentaires permettront de préciser le rôle de ce virus, possiblement systémique, dans d’autres affections. Abstract Human Bocavirus (HboV) was recently cloned by a systematic screening of nasopharyngeal samples from children hospitalized for respiratory tract infections. This virus, genus Bocavirus, family Parvoviridae, was identified by screening for its DNA in 5% of nasopharyngeal aspirates, as reported in several studies. It may be responsible for upper and lower respiratory tract infections of young children under five years with a peak rate in winter. Because of a high rate of viral co-infections, its pathogenic role in these infections should be documented. Further studies are required to determine the role of this possibly systemic virus in other affections.


title: Principles of mental health care during the COVID-19 pandemic

text: We describe the basic principles of mental health care during the COVID-19 pandemic that should be endorsed by the mental health professional associations and incorporated in the health strategies for the management of the COVID-19 pandemic. The main principle is that there should be no substantial differences in the provision of health care for COVID-19 between persons with pre-existing mental health disorders and the ones without previous disorders. Subsequently, the organization of the health care should reflect that as well. These principles should (a) prevent the possible effects of stigmatizing attitudes toward mental health issues, possibly leading to potentially deleterious situations, such as psychiatric patients being treated (even temporarily) separately from other patients, in psychiatric facilities, where the staff is not equipped and trained adequately for the management of COVID-19; (b) highlight the fact that patients with mental health disorders are at greater risk for developing serious complications of COVID-19 infection due to other factors—they often smoke and have comorbidities such as hypertension, diabetes, all associated with higher morbidity and mortality from COVID-19 infection; (c) highlight that measures should be taken to minimize the risk of the spread of infection in psychiatric wards/institutions; (d) provide a general framework for the reorganization of mental health services toward the provision of services for persons in need, including frontline medical workers and patients with COVID-19 without previous mental health problems as well as for persons with pre-existing mental health problems under new circumstances of pandemic.