title: Intervention Serology and Interaction Substitution: Modeling the Role of ‘Shield Immunity’ in Reducing COVID-19 Epidemic Spread

text: The COVID-19 pandemic has precipitated a global crisis, with more than 690,000 confirmed cases and more than 33,000 confirmed deaths globally as of March 30, 2020 [1–4]. At present twOfficentral public health control strategies have emerged: mitigation and suppression (e.g, [5]). Both strategies focus on reducing new infections by reducing interactions (and both raise questions of sustainability and long-term tactics). Complementary to those approaches, here we develop and analyze an epidemiological intervention model that leverages serological tests [6, 7] to identify and deploy recovered individuals as focal points for sustaining safer interactions via interaction substitution, i.e., to develop what we term ‘shield immunity’ at the population scale. Recovered individuals, in the present context, represent those who have developed protective, antibodies to SARS-CoV-2 and are no longer shedding virus [8]. The objective of a shield immunity strategy is to help sustain the interactions necessary for the functioning of essential goods and services (including but not limited to tending to the elderly [9], hospital care, schools, and food supply) while decreasing the probability of transmission during such essential interactions. We show that a shield immunity approach may significantly reduce the length and reduce the overall burden of an outbreak, and can work synergistically with social distancing. The present model highlights the value of serological testing as part of intervention strategies, in addition to its well recognized roles in estimating prevalence [10, 11] and in the potential development of plasma-based therapies [12–15].


title: Tackling influenza with broadly neutralizing antibodies

text: Monoclonal antibodies have revolutionized the treatment of several human diseases, including cancer, autoimmunity and inflammatory conditions and represent a new frontier for the treatment of infectious diseases. In the last decade, new methods have allowed the efficient interrogation of the human antibody repertoire from influenza immune individuals and the isolation of several monoclonal antibodies capable of dealing with the high variability of influenza viruses. Here, we will provide a comprehensive overview of the specificity, antiviral and immunological mechanisms of action and development into the clinic of broadly reactive monoclonal antibodies against influenza A and B viruses.


title: Human Lung Spheroids as In Vitro Niches of Lung Progenitor Cells with Distinctive Paracrine and Plasticity Properties

text: Basic and translational research on lung biology has discovered multiple progenitor cell types, specialized or facultative, responsible for turnover, renewal, and repair. Isolation of populations of resident lung progenitor cells (LPCs) has been described by multiple protocols, and some have been successfully applied to healthy human lung tissue. We aimed at understanding how different cell culture conditions may affect, in vitro, the phenotype of LPCs to create an ideal niche‐like microenvironment. The influence of different substrates (i.e., fibronectin, gelatin, laminin) and the impact of a three‐dimensional/two‐dimensional (3D/2D) culture switch on the biology of LPCs isolated as lung spheroids (LSs) from normal adult human lung biopsy specimens were investigated. We applied a spheroid culture system as the selective/inductive step for progenitor cell culture, as described in many biological systems. The data showed a niche‐like proepithelial microenvironment inside the LS, highly sensitive to the 3D culture system and significantly affecting the phenotype of adult LPCs more than culture substrate. LSs favor epithelial phenotypes and LPC maintenance and contain cells more responsive to specific commitment stimuli than 2D monolayer cultures, while secreting a distinctive set of paracrine factors. We have shown for the first time, to our knowledge, how culture as 3D LSs can affect LPC epithelial phenotype and produce strong paracrine signals with a distinctive secretomic profile compared with 2D monolayer conditions. These findings suggest novel approaches to maintain ex vivo LPCs for basic and translational studies. Stem Cells Translational Medicine 2017;6:767–777


title: Co‐localization of angiotensin‐converting enzyme 2‐, octomer‐4‐ and CD34‐positive cells in rabbit atherosclerotic plaques

text: Angiotensin‐converting enzyme 2 (ACE2) is a novel enzyme with possible implications in the treatment of blood pressure disorders. Recent evidence suggests that an upregulation of ACE2 can be stimulated by all‐trans retinoic acid (at‐RA); however, at‐RA also affects regulation of the stem‐cell marker octomer‐4 (Oct‐4) and thus cellular differentiation. We have previously shown that smooth muscle cells and macrophages present within rabbit atherosclerotic plaques are positive for ACE2, Oct‐4 and the haematopoietic stem‐cell marker CD34. Thus, to provide evidence that possible at‐RA treatment could affect both plaque cellular biology (via effects on cellular differentiation) and blood pressure (via ACE2), it is vital to show that cells with atherosclerotic plaques co‐express all three markers. Thus, we sought to provide evidence that a subset of cells within atherosclerotic plaques is positive for ACE2, Oct‐4 and CD34. We used New Zealand White rabbits that were fed a control diet supplemented with 0.5% cholesterol plus 1% methionine for 4 weeks and then allowed to consume a normal diet for 10 weeks. Immunohistochemistry was performed by standard techniques. We report that ACE2, Oct‐4 and CD34 were all present within atherosclerotic plaques. Although macrophages were positive for all three markers, spindle‐shaped cells in the media did not show all three markers. The endothelium overlying normal arterial wall showed positive Oct‐4 and ACE2 immunoreactivity, but CD34 immunoreactivity was patchy, indicating that such cells might not have fully differentiated. It is concluded that cells in atherosclerotic plaques express co‐express ACE2, Oct‐4 and CD34. Further studies aimed at establishing the effects of all‐trans retinoic acid on blood pressure and atherosclerotic cell differentiation are warranted.


title: How long do nosocomial pathogens persist on inanimate surfaces? A systematic review

text: BACKGROUND: Inanimate surfaces have often been described as the source for outbreaks of nosocomial infections. The aim of this review is to summarize data on the persistence of different nosocomial pathogens on inanimate surfaces. METHODS: The literature was systematically reviewed in MedLine without language restrictions. In addition, cited articles in a report were assessed and standard textbooks on the topic were reviewed. All reports with experimental evidence on the duration of persistence of a nosocomial pathogen on any type of surface were included. RESULTS: Most gram-positive bacteria, such as Enterococcus spp. (including VRE), Staphylococcus aureus (including MRSA), or Streptococcus pyogenes, survive for months on dry surfaces. Many gram-negative species, such as Acinetobacter spp., Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, Serratia marcescens, or Shigella spp., can also survive for months. A few others, such as Bordetella pertussis, Haemophilus influenzae, Proteus vulgaris, or Vibrio cholerae, however, persist only for days. Mycobacteria, including Mycobacterium tuberculosis, and spore-forming bacteria, including Clostridium difficile, can also survive for months on surfaces. Candida albicans as the most important nosocomial fungal pathogen can survive up to 4 months on surfaces. Persistence of other yeasts, such as Torulopsis glabrata, was described to be similar (5 months) or shorter (Candida parapsilosis, 14 days). Most viruses from the respiratory tract, such as corona, coxsackie, influenza, SARS or rhino virus, can persist on surfaces for a few days. Viruses from the gastrointestinal tract, such as astrovirus, HAV, polio- or rota virus, persist for approximately 2 months. Blood-borne viruses, such as HBV or HIV, can persist for more than one week. Herpes viruses, such as CMV or HSV type 1 and 2, have been shown to persist from only a few hours up to 7 days. CONCLUSION: The most common nosocomial pathogens may well survive or persist on surfaces for months and can thereby be a continuous source of transmission if no regular preventive surface disinfection is performed.


title: Viral agents of acute gastroenteritis in hospitalized children in Greece

text: Abstract A 6-year study of stool samples from 4604 children hospitalized for acute gastroenteritis was conducted to investigate the role of enteric viruses as a cause of gastroenteritis in north-west Greece. Rotaviruses, noroviruses, adenoviruses and astroviruses were detected in 21.35%, 4%, 3.5% and 2.35%, respectively, by enzyme immunoassays and molecular techniques. Molecular techniques enhanced overall diagnostic efficacy by 2.5%, and by c. 10% each for rotavirus and adenovirus. Rotavirus was the leading cause of viral gastroenteritis, usually associated with severe illness. Mixed infections were found in 4.4% of positive specimens, and rotavirus plus astrovirus represented the most frequent co-infection (55.5%). This first study on the epidemiology of viral gastroenteritis in Greece shows that recent advances in the diagnosis of viral enteropathogens may have only marginal effects on overall diagnostic efficacy, and thus the impact of viral agents causing sporadic gastroenteritis in public health cannot be fully evaluated.


title: Detection of Astrovirus in a Cow with Neurological Signs by Nanopore Technology, Italy

text: In this study, starting from nucleic acids purified from the brain tissue, Nanopore technology was used to identify the etiological agent of severe neurological signs observed in a cow which was immediately slaughtered. Histological examination revealed acute non-suppurative encephalomyelitis affecting the brainstem, cerebrum, cerebellum, and medulla oblongata, while by using PCR-based assays, the nucleic acids of major agents for neurological signs were not detected. By using Nanopore technology, 151 sequence reads were assigned to Bovine Astrovirus (BoAstV). Real-time RT-PCR and in situ hybridization (ISH) confirmed the presence of viral RNA in the brain. Moreover, using the combination of fluorescent ISH and immunofluorescence (IF) techniques, it was possible to detect BoAstV RNA and antigens in the same cells, suggesting the active replication of the virus in infected neurons. The nearly whole genome of the occurring strain (BoAstV PE3373/2019/Italy), obtained by Illumina NextSeq 500, showed the highest nucleotide sequence identity (94.11%) with BoAstV CH13/NeuroS1 26,730 strain, an encephalitis-associated bovine astrovirus. Here, we provide further evidence of the role of AstV as a neurotropic agent. Considering that in a high proportion of non-suppurative encephalitis cases, which are mostly indicative of a viral infection, the etiologic agent remains unknown, our result underscores the value and versatility of Nanopore technology for a rapid diagnosis when the PCR-based algorithm gives negative results.


title: Tools to therapeutically harness the human antibody response

text: The natural human antibody response is a rich source of highly specific, neutralizing and self-tolerant therapeutic reagents. Recent advances have been made in isolating and characterizing monoclonal antibodies that are generated in response to natural infection or vaccination. Studies of the human antibody response have led to the discovery of crucial epitopes that could serve as new targets in vaccine design and in the creation of potentially powerful immunotherapies. With a focus on influenza virus and HIV, herein we summarize the technological tools used to identify and characterize human monoclonal antibodies and describe how these tools might be used to fight infectious diseases.


title: Disaster management, crowdsourced R&D and probabilistic innovation theory: Toward real time disaster response capability

text: Abstract General agreement exists effective disaster management faces constraints related to knowledge sharing and a need for real-time research responses. Extreme case examples of disasters especially vulnerable to these challenges are global pandemics, or disease outbreaks, in which data required for research response are only available after the start of an outbreak. This paper argues the developing field of probabilistic innovation (innovation increasing probability of solving societal problems through radically increasing coordination of volumes of problem-solving inputs and analysis), and its methodologies, such as those drawing from crowdsourced R&D and social media, may offer useful insights into enabling real time research capabilities, with important implications for disaster and crisis management. Three paradigms of disaster research are differentiated, as literature is related to theory offered by post normal science, Kuhnian ‘normal science’ and Lakatosian ‘structural science,’ and the goal of achieving real time research problem solving capacity in disaster crisis situations. Global collaborative innovation platforms and large-scale investments in emerging crowdsourced R&D and social media technologies together with synthesis of appropriate theory may contribute to improved real time disaster response and resilience across contexts, particularly in instances where data required to manage response is only available after disasters unfold.


title: HIV and risk of COVID-19 death: a population cohort study from the Western Cape Province, South Africa

text: BACKGROUND: The effect of HIV co-infection on COVID-19 outcomes in sub-Saharan Africa is unknown METHODS: We conducted a population cohort study using linked data from adults attending public sector health facilities in the Western Cape, South Africa We used Cox-proportional hazards models adjusted for age, sex, location and comorbidities to examine the association between HIV and COVID-19 death among (i) public sector 'active patients' (at least 1 health visit in the 3 years before March 2020), (ii) laboratory-diagnosed COVID-19 cases and (iii) hospitalized COVID-19 cases COVID-19 was diagnosed with SARS-CoV-2 PCR tests We calculated the standardized mortality ratio (SMR) for COVID-19 comparing HIV positive vs negative adults using modelled population estimates RESULTS: Among 3,460,932 public sector patients (16% HIV positive), 22,308 were diagnosed with COVID-19, of whom 625 died In adjusted analysis, HIV increased risk of COVID-19 mortality (adjusted hazard ratio [aHR]:2 14;95% confidence interval [CI]:1 70;2 70), with similar risks across strata of viral load and immunosuppression increased HIV-associated risk of COVID-19 death remained when restricting to COVID-19 cases (aHR:1 70;95%CI:132;2 18) or hospitalized cases (aHR:1 45;95%CI:1 14;1 84) Current and previous tuberculosis also increased COVID-19 mortality risk (aHR [95%CI]:2 70 [1 81;4 04] and 1 51 [1 18;1 93] respectively) The SMR for COVID-19 death associated with HIV was 2 39 (95% CI:1 96;2 86);population attributable fraction 8 5% (95%CI:6 1;11 1) CONCLUSION: HIV was associated with a doubling of COVID-19 mortality risk While our findings may over-estimate the HIV-associated risk COVID-19 death due to residual confounding, people with HIV should be considered a high-risk group for COVID-19 management


title: Coronavirus and Other Respiratory Illnesses Comparing Older with Young Adults

text: Abstract Background Study of human coronavirus and other virus-associated respiratory illnesses is needed to describe their clinical effects on chronically ill, older adults. Methods A prospective study during 2009 to 2013 clinically assessed acute respiratory illnesses soon after onset and 3 to 4 weeks later in patients aged ≥60 years with chronic lung and heart diseases (group 1, 100 subjects) and healthy adults aged 18 to 40 years (group 2, 101 subjects). Respiratory secretions were tested for nucleic acids of a panel of respiratory viruses. An increase in antibody titer was assessed for 4 coronavirus strains. Results Virus-associated illnesses (29 [39.1%] of 74 illnesses in group 1 and 59 [48.7%] of 121 illnesses in group 2) occurred in all calendar quarters, most commonly in the first and fourth quarters. Coronaviruses (group 1: 14 [18.9%] illnesses; group 2: 26 [21.5%] illnesses) and enteroviruses/rhinoviruses (group 1: 14 [18.9%] illnesses; group 2: 37 [30.6%] illnesses) were most common. Virus co-infections occurred in 10 illnesses. Illnesses with 9 to 11 symptoms were more common in group 1 (17 [23.0%]) than in group 2 (15 [12.4%]) (P < .05). Compared with group 2, more group 1 subjects reported dyspnea, more severe disease of longer duration, and treatment for acute illness with prednisone and antibiotics. Coronavirus-associated illnesses (percent of illnesses, group 1 vs group 2) were characterized by myalgias (21% vs 68%, P < .01), chills (50% vs 52%), dyspnea (71% vs 24%, P < .01), headache (64% vs 72%), malaise (64% vs 84%), cough (86% vs 68%), sputum production (86% vs 60%), sore throat (64% vs 80%), and nasal congestion (93% vs 96%). Conclusions Respiratory illnesses were commonly associated with coronaviruses and enteroviruses/rhinoviruses affecting chronically ill, older patients more than healthy, young adults.


title: Megaesophagus Is a Major Pathological Condition in Rats With a Large Deletion in the Rbm20 Gene

text: A spontaneously arising, loss-of-function mutation in the RNA binding motif protein 20 (Rbm20) gene, which encodes a nuclear splicing protein, was previously identified as the underlying reason for expression of an abnormally large TITIN (TTN) protein in a rat model of cardiomyopathy. An outbreak of Pseudomonas aeruginosa led to submission of rats with dyspnea, sneezing, lethargy, nasal discharge, and/or unexpected death for diagnostic evaluation. Necropsy revealed underlying megaesophagus in Rbm20(–/–) rats. Further phenotyping of this rat strain and determination of the size of esophageal TTN was undertaken. The Rbm20-defective rats developed megaesophagus at an early age (26 weeks) with high frequency (13/32, 41%). They also often exhibited secondary rhinitis (9/32, 28%), aspiration pneumonia (8/32, 25%), and otitis media/interna (6/32, 19%). In addition, these rats had a high prevalence of hydronephrosis (13/32, 41%). RBM20 is involved in splicing multiple RNA transcripts, one of which is the muscle-specific protein TTN. Rbm20 mutations are a significant cause of dilated cardiomyopathy in humans. In Rbm20-defective rats, TTN size was significantly increased in the skeletal muscle of the esophagus. Megaesophagus in this rat strain (maintained on a mixed genetic background) is hypothesized to result from altered TTN stretch signaling in esophageal skeletal muscle. This study describes a novel mechanism for the development of megaesophagus, which may be useful for understanding the pathogenesis of megaesophagus in humans and offers insights into potential myogenic causes of this condition. This is the first report of megaesophagus and other noncardiac pathogenic changes associated with mutation of Rbm20 in any species.


title: SARS Risk Perception, Knowledge, Precautions, and Information Sources, the Netherlands

text: Severe acute respiratory syndrome (SARS)–related risk perceptions, knowledge, precautionary actions, and information sources were studied in the Netherlands during the 2003 SARS outbreak. Although respondents were highly aware of the SARS outbreak, the outbreak did not result in unnecessary precautionary actions or fears.


title: Mass spectrometric approaches to study enveloped viruses: New possibilities for structural biology and prophylactic medicine

text: This review considers principles of the use of mass spectrometry for the study of biological macromolecules. Some examples of protein identification, virion proteomics, testing vaccine preparations, and strain surveillance are represented. Possibilities of structural characterization of viral proteins and their posttranslational modifications are shown. The authors’ studies by MALDI-MS on S-acylation of glycoproteins from various families of enveloped viruses and on oligomerization of the influenza virus hemagglutinin transmembrane domains are summarized.


title: Convalescent Plasma Therapy: Helpful Treatment of COVID‐19 in a Kidney Transplant Recipient presenting with serve clinical manifestation and complex complications

text: The latest study observed that KTRs with COVID‐19 had a higher early mortality than persons with COVID‐19 in the general population([1]). To date, there is no specific drugs. Previous studies showed convalescent plasma could help patient recovery from SARS([2, 3]). However, only a very limit evidences has been showed it is effective in COVID‐19 treatment([4, 5]). Here, we describe the first successful recovery of case of COVID‐19 in a KTR treated with convalescent plasma therapy.


title: Effects of disinfection on the molecular detection of porcine epidemic diarrhea virus

text: Abstract Routine detection of porcine epidemic diarrhea virus (PEDV) is currently limited to RT-PCR but this test cannot distinguish between viable and inactivated virus. We evaluated the capability of disinfectants to both inactivate PEDV and sufficiently damage viral RNA beyond RT-PCR detection. Five classes of disinfectants (phenol, quaternary ammonium compound, sodium hypochlorite, oxidizing agent, and quaternary ammonium/glutaraldehyde combination) were evaluated in vitro at varying concentrations, both in the presence and absence of swine feces, and at three different temperatures. No infectious PEDV was recovered after treatment with evaluated disinfectants. Additionally, all tested disinfectants except for 0.17% sodium hypochlorite dramatically reduced qRT-PCR values. However, no disinfectants eliminated RT-PCR detection of PEDV across all replicates; although, 0.52%, 1.03% and 2.06% solutions of sodium hypochlorite and 0.5% oxidizing agent did intermittently produce RT-PCR negatives. To simulate field conditions in a second aim, PEDV was applied to pitted aluminum coupons, which were then treated with either 2.06% sodium hypochlorite or 0.5% oxidizing agent. Post-treatment surface swabs of the coupons tested RT-PCR positive but were not infectious to cultured cells or naïve pigs. Ultimately, viable PEDV was not detected following application of each of the tested disinfectants, however in most cases RT-PCR detection of viral RNA remained. RT-PCR detection of PEDV is likely even after disinfection with many commercially available disinfectants.


title: Pangolin homology associated with 2019-nCoV

text: To explore potential intermediate host of a novel coronavirus is vital to rapidly control continuous COVID-19 spread. We found genomic and evolutionary evidences of the occurrence of 2019-nCoV-like coronavirus (named as Pangolin-CoV) from dead Malayan Pangolins. Pangolin-CoV is 91.02% and 90.55% identical at the whole genome level to 2019-nCoV and BatCoV RaTG13, respectively. Pangolin-CoV is the lowest common ancestor of 2019-nCoV and RaTG13. The S1 protein of Pangolin-CoV is much more closely related to 2019-nCoV than RaTG13. Five key amino-acid residues involved in the interaction with human ACE2 are completely consistent between Pangolin-CoV and 2019-nCoV but four amino-acid mutations occur in RaTG13. It indicates Pangolin-CoV has similar pathogenic potential to 2019-nCoV, and would be helpful to trace the origin and probable intermediate host of 2019-nCoV.


title: The Imperfect Cytokine Storm: Severe COVID-19 with ARDS in Patient on Durable LVAD Support

text: Abstract As health systems worldwide grapple with the COVID-19 pandemic, patients on durable LVAD support represent a unique population at risk for the disease. We outline such a patient who developed COVID-19 complicated by “cytokine storm” with severe ARDS and myocardial injury; and describe the challenges that arose during management.


title: Insights on cross-species transmission of SARS-CoV-2 from structural modeling

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global pandemic that has infected more than 6 million people in more than 180 countries worldwide. Like other coronaviruses, SARS-CoV-2 is thought to have been transmitted to humans from wild animals. Given the scale and widespread geographical distribution of the current pandemic, the question emerges whether human-to-animal transmission is possible and if so, which animal species are most at risk. Here, we investigated the structural properties of several ACE2 orthologs bound to the SARS-CoV-2 spike protein. We found that species known not to be susceptible to SARS-CoV-2 infection have non-conservative mutations in several ACE2 amino acid residues that disrupt key polar and charged contacts with the viral spike protein. Our models also predict affinity-enhancing mutations that could be used to design ACE2 variants for therapeutic purposes. Finally, our study provides a blueprint for modeling viral-host protein interactions and highlights several important considerations when designing these computational studies and analyzing their results.


title: Clinical aspects of influenza A(H1N1)pdm09 cases reported during the pandemic in Brazil, 2009-2010

text: OBJECTIVE: To describe the clinical aspects of cases of influenza A(H1N1)pdm09 in Brazil. METHODS: A descriptive study of cases reported in Sistema de Informação de Agravos de Notificação (SINAN), 2009-2010. RESULTS: As the final classification, we obtained 53,797 (56.79%) reported cases confirmed as a new influenza virus subtype, and 40,926 (43.21%) cases discarded. Fever was the most common sign, recorded in 99.74% of the confirmed and 98.92% of the discarded cases. Among the confirmed cases, the presence of comorbidities was reported in 32.53%, and in 38.29% of the discarded cases. The case fatality rate was 4.04%; 3,267 pregnant women were confirmed positive for influenza A new viral subtype and 2,730 of them were cured. The case fatality rate of pregnant women was 6.88%. CONCLUSION: The findings suggested concern of the health system with pregnant women, and patients with comorbidities and quality of care may have favored a lower mortality. We recommend that, when caring for patients with severe respiratory symptoms, with comorbidities, or pregnant women, health professionals should consider the need for hospital care, as these factors make up a worse prognosis of infection by the pandemic influenza virus.


title: Electrolyte transport in piglets infected with transmissible gastroenteritis virus Stimulation by verapamil and clonidine

text: Abstract The effects of clonidine, an α 2-adrenergic agonist, and verapamil, a Ca2+ channel blocker, on Na2+ and Cl− absorption were studied in stripped jejunal mucosa from control and transmissible-gastroenteritis-virus-infected piglets. All infected piglets developed severe diarrhea 18–24 hours after oral inoculation. Jejunum from infected animals, as compared with control jejunum, had decreased mucosal-to-serosal, serosal-to-mucosal, and net Na+ and Cl− fluxes. Clonidine and verapamil caused a decrease in short-circuit current and stimulation of Na+ and Cl− absorption in control jejunum. In infected piglets, although the jejunum exhibited severe villus atrophy, both drugs stimulated Na+ and Cl− absorption and the magnitude of Na+ and Cl− absorption was similar in control and transmissible-gastroenteritis-infected jejunum. In contrast, d-glucose stimulated Na+ absorption, and the decrease in shortcircuit current caused by verapamil and clonidine, were decreased in transmissible-gastroenteritis-infected jejunum. Such pharmacological stimulation of Na+ and Cl− absorption might be useful in the management and treatment of certain viral diarrheal diseases.


title: Cellular Reservoirs for Coronavirus Infection of the Brain in β(2)-Microglobulin Knockout Mice

text: Mouse hepatitis virus (MHV) A59 infection which causes acute encephalitis, hepatitis, and chronic demyelination, is one of the experimental models for multiple sclerosis. Previous studies showed that lethal infection of β(2)-microglobulin ‘knockout’ (β(2)M(-/-)) mice required 500-fold less virus and viral clearance was delayed as compared to infection of immunocompetent C57Bl/6 (B6) mice. To investigate the mechanism of the increased susceptibility of β(2)M(-/-) mice to MHV-A59, we studied organ pathology and the distribution of viral antigen and RNA during acute and chronic infection. A59-infected β(2)M(-/-) mice were more susceptible to acute encephalitis and hepatitis, but did not have increased susceptibility to demyelination. Viral antigen and RNA distribution in the brain was increased in microglia, lymphocytes, and small vessel endothelial cells while the distribution in neurons and glia was similar in β(2)M(-/-) mice and B6 mice. Acute hepatitis and thymus cortical hypoplasia in β(2)M(-/-) mice were delayed in onset but pathologic changes in these organs were similar to those in B6 mice. The low rate of demyelination in β(2)M(-/-) mice was consistent with the low dose of the virus given. A less neurotropic virus MHV-2, caused increased parenchymal inflammation in β(2)M(-/-) mice, but without demyelination. Thus, CD8+ cells were important for viral clearance from endothelial cells, microglia and inflammatory cells, but not from neuronal and glial cells. In addition, CD8+ cells played a role in preventing the spread of encephalitis.


title: Wildlife Trade and Global Disease Emergence

text: The global trade in wildlife provides disease transmission mechanisms that not only cause human disease outbreaks but also threaten livestock, international trade, rural livelihoods, native wildlife populations, and the health of ecosystems. Outbreaks resulting from wildlife trade have caused hundreds of billions of dollars of economic damage globally. Rather than attempting to eradicate pathogens or the wild species that may harbor them, a practical approach would include decreasing the contact rate among species, including humans, at the interface created by the wildlife trade. Since wildlife marketing functions as a system of scale-free networks with major hubs, these points provide control opportunities to maximize the effects of regulatory efforts.


Is CoronavirusDisease 2019 (COVID-19) Seen Less in Countries More Exposed to Malaria?


title: Epidemiological aspects of antibiotic resistance in respiratory pathogens

text: Abstract Respiratory infections are the most frequent reason for primary health care consultation. The main causes of respiratory tract infections in children are viruses and the most common types are upper respiratory tract infections: common cold, pharyngitis, otitis media and sinusitis. Pneumonia is much more serious. As well as viruses, bacteria are often involved in respiratory tract infections. Three bacterial species are most commonly isolated: Streptococcus pneumoniae, non-encapsulated Haemophilus influenzae and Moraxella (Branhamella) catarrhalis. The most common bacterial cause of pharyngitis is Streptococcus pyogenes. Bacteria isolated from community-acquired infection usually are sensitive to the majority of suitable drugs, but during the past two decades, significant antibiotic resistance has emerged. Resistance to penicillins has spread among H. influenzae and S. pneumoniae. The mechanism of penicillin resistance in H. influenzae is mainly by production of β-lactamases TEM-1 and ROB-1, whereas in S. pneumoniae resistance is an effect of the changes in penicillin binding proteins. Among respiratory pathogens, resistance to tetracyclines, macrolides, trimethoprim–sulphamethoxazole and fluoroquinolones has also appeared. Several mechanisms depending on changes in target, active efflux and modifying enzymes are involved.


title: Impact of the 2015 Middle East Respiratory Syndrome Outbreak on Emergency Care Utilization and Mortality in South Korea

text: PURPOSE: In May 2015, South Korea experienced an epidemic of Middle East respiratory syndrome (MERS). This study investigated the impacts of MERS epidemic on emergency care utilization and mortality in South Korea. MATERIALS AND METHODS: A natural experimental study was conducted using healthcare utilization and mortality data of the entire Korean population. The number of monthly emergency room (ER) visits was investigated to identify changes in emergency care utilization during the MERS epidemic; these trends were also examined according to patients' demographic factors, disease severity, and region. Deaths within 7 days after visiting an ER were analyzed to evaluate the impact of the reduction in ER visits on mortality. RESULTS: The number of ER visits during the peak of the MERS epidemic (June 2015) decreased by 33.1% compared to the average figures from June 2014 and June 2016. The decrease was observed in all age, sex, and income groups, and was more pronounced for low-acuity diseases (acute otitis media: 53.0%; upper respiratory infections: 45.2%) than for high-acuity diseases (myocardial infarctions: 14.0%; ischemic stroke: 16.6%). No substantial changes were detected for the highest-acuity diseases, with increases of 3.5% for cardiac arrest and 2.4% for hemorrhagic stroke. The number of deaths within 7 days of an ER visit did not change significantly. CONCLUSION: During the MERS epidemic, the number of ER visits decreased in all age, sex, and socioeconomic groups, and decreased most sharply for low-acuity diseases. Nonetheless, there was no significant change in deaths after emergency care.


title: Antiviral activity of zinc salts against transmissible gastroenteritis virus in vitro

text: Abstract Zinc has been shown to mediate antiviral effects against certain viruses. However, the underlying mechanisms are still largely unknown. We investigated the effects of the two zinc salts, zinc chloride (ZnCl2) and zinc sulfate (ZnSO4), on infection of swine testicle (ST) cells with transmissible gastroenteritis virus (TGEV) and compared it to the effects of a control salt, magnesium sulfate (MgSO4). Virus yield reduction experiments showed that ZnCl2 and ZnSO4 did not exhibit direct virucidal effects and did not affect adsorption of TGEV to ST cells. However, ZnCl2 and ZnSO4 markedly reduced viral titers as well as TGEV RNA and viral protein synthesis when applied during virus penetration and at different time points after viral cell entry. The results of the study suggest that zinc salts do not interfere with TGEV-cell binding but that they mediate antiviral effects through inhibition of viral penetration or egress or the intracellular phase of the viral life-cycle.


Breast Reconstruction and the Covid-19 Pandemic: A Viewpoint


title: Identification of intertypic recombinant infectious bronchitis viruses from slaughtered chickens

text: Avian coronavirus infectious bronchitis virus (IBV) poses a major threat to the global poultry industry. New IBV geno- and serotypes are continually reported. However, information on IBV prevalence is not frequently addressed in these reports. This study reports on a viral surveillance program in Taiwan from 2005 to 2006 with sampling conducted in poultry slaughterhouses. The genetic features of the obtained field isolates were investigated using sequence analysis and SimPlot analysis. A 1-directional neutralization test was performed to examine the antigenic variations among the collected viruses. The selection pressures that may contribute to the evolution of Taiwan IBV during recent decades were assessed. The surveillance program revealed that 8 out of 47 flocks (17%) were IBV-infected, from which 13 IBV isolates were recovered. Based on the phylogenetic analysis of the S1 gene, 11 of 13 isolates (84.6%) clustered with Taiwan group I. One IBV isolate showed evidence of frequent recombination events with China-like IBV in the spike glycoprotein (S) gene. Another isolate demonstrated the incorporation of China-like and H120-like genome fragments within the S2 gene and the membrane protein (M) gene region, respectively. Some antigenic changes were found in the 1-directional neutralization test. However, no positive selection pressures were related to those variations in the S1 genes among Taiwan IBV. Based on our work, we suggest that sampling chickens in poultry slaughterhouses is an effective and valuable means of compiling viral prevalence data, particularly in situations where there is subclinical infection. Infectious bronchitis viruses from slaughtered chickens revealed intertypic genetic recombination and antigenic diversity.


title: Cryptosporidium outbreak in calves on a large dairy farm: Effect of treatment and the association with the inflammatory response and short-term weight gain

text: Abstract Cryptosporidium spp. infections in neonatal dairy calves can cause diarrhoea and, in rare cases, death. The infection is usually self-limiting, but halofuginone lactate (HL) can be used prophylactically. Calves (n =144) in the study were born during a 2-month period on one farm. A total of 901 serum and 767 faecal samples were collected. Based on HL treatment, the calves were divided into 3 groups: I) not treated, II) treated incorrectly (treatment started >48h after birth, or lasted <7days), and III) treated correctly (started <48h after birth, and lasted ≥7days). Over the 3-month observation period, 14.6% (n =21) of the calves died, of which most (67%) had not been treated with HL. Correctly performed treatment of cryptosporidiosis significantly delayed the onset of oocysts shedding (P <0.001) and reduced haptoglobin (HP) and serum amyloid A (SAA) concentrations in the second week of life. HP concentration and HL treatment were negatively associated with weight gain at 3months of age. Cryptosporidium positive faecal samples were significantly (P <0.001) more likely to be diarrhoeic but Giardia or Eimeria positive samples were not. Correct prophylactic treatment with HL delayed the shedding of Cryptosporidium oocysts and improved survival, but was negatively associated with weight gain. Incorrect treatment had a low impact on mortality and resembled no treatment regarding the proportion of calves shedding oocysts. Acute phase response (APR) in the second week of life seemed to be positively associated with shedding high amounts of Cryptosporidium oocysts.


title: Placental Pathology in COVID-19

text: OBJECTIVES: To describe histopathologic findings in the placentas of women with coronavirus disease 2019 (COVID-19) during pregnancy. METHODS: Pregnant women with COVID-19 delivering between March 18, 2020, and May 5, 2020, were identified. Placentas were examined and compared to historical controls and women with placental evaluation for a history of melanoma. RESULTS: Sixteen placentas from patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were examined (15 with live birth in the third trimester, 1 delivered in the second trimester after intrauterine fetal demise). Compared to controls, third trimester placentas were significantly more likely to show at least one feature of maternal vascular malperfusion (MVM), particularly abnormal or injured maternal vessels, and intervillous thrombi. Rates of acute and chronic inflammation were not increased. The placenta from the patient with intrauterine fetal demise showed villous edema and a retroplacental hematoma. CONCLUSIONS: Relative to controls, COVID-19 placentas show increased prevalence of decidual arteriopathy and other features of MVM, a pattern of placental injury reflecting abnormalities in oxygenation within the intervillous space associated with adverse perinatal outcomes. Only 1 COVID-19 patient was hypertensive despite the association of MVM with hypertensive disorders and preeclampsia. These changes may reflect a systemic inflammatory or hypercoagulable state influencing placental physiology.


title: Detection and differentiation of virulent and avirulent strains of Newcastle disease virus by real-time PCR

text: Abstract A rapid diagnostic method based on the melting curve SYBR Green I real-time PCR analysis was developed to detect and differentiate Newcastle disease virus (NDV) strains. Degenerated primers based on the cleavage site sequence of the F0 gene were designed to detect specific sequences characteristic of virulent and avirulent strains of NDV. Eighteen strains of NDV from four lineages were identified and grouped into virulent and avirulent strains. Peaks on the melting temperature graph with melting temperature values between 80.00 and 83.80°C were observed for lentogenic (avirulent) strains. T m values higher than 83.80 were observed for virulent (mesogenic and velogenic) strains. The detection limit of real-time PCR was 2×102 plasmid copies per reaction or 102 EID50 for velogenic strains and 103 EID50 for lentogenic strains. The results obtained in this study demonstrate the possible applications for melting curve real-time PCR analysis in laboratory practice for the diagnosis and differentiation of avirulent and virulent strains of Newcastle disease virus.


title: Rapid optimization of antimicrobial chemotherapy given to pediatric patients with community-acquired pneumonia using PCR techniques with serology and standard culture

text: Abstract Children (n =117; mean age 2.4 ± 2.9 years) were diagnosed as having community-acquired pneumonia (CAP) using clinical symptoms, chest X-rays, and hematological data. The causative pathogen was determined using real-time polymerase chain reaction (PCR) (6 bacteria), multiple reverse transcription-PCR (MPCR; 11 viruses), bacterial culture, and serology. The initial chemotherapy was evaluated based on the pathogens identified using PCR. We found 27 viral cases (23.1%), 25 bacterial cases (21.4%), 45 mixed infections with virus and bacteria (38.5%), 10 Mycoplasma pneumoniae (8.5%), 7 mixed infections with M. pneumoniae and another pathogen (6.0%), 1 Chlamydophila pneumoniae (0.9%), and 2 unknown pathogens (1.7%). Streptococcus pneumoniae and Haemophilus influenzae accounted for 58 (49.5%) and 27 (23.0%) of the cases, respectively. The median values (50%) of the white blood cell count (WBC) and C-reactive protein (CRP) using the box-and-whisker and plot method, respectively, were 11.7 × 103 mm−3 and 1.4mg/dl in viral infections, 15.6 × 103 mm−3 and 4.8mg/dl in mixed infections with virus and bacteria, 17.8 × 103 mm−3 and 6.3mg/dl in bacterial infections, 6.7 × 103 mm−3 and 1.4mg/dl in M. pneumoniae infections, and 21.5 × 103 mm−3 and 6.4mg/dl in mixed infections with M. pneumoniae and other bacterial infections. Sulbactam/ampicillin (n =61), carbapenems (n =12), and ceftriaxone (n =7) were selected for the patients suspected of having bacterial infections alone or mixed infections with bacterial and viruses in accordance with our criteria defined tentatively. For those with M. pneumoniae and C. pneumoniae infections, azithromycin or minocycline was initially used. Treatments averaged 3–5 days. The empirical chemotherapy was improper in 9.4% of cases in relation to the etiologic agents finally identified. We conclude that rapid and comprehensive identification using PCR can provide optimal antimicrobial chemotherapy for CAP patients.


title: Genetic aspects of macrophage involvement in natural resistance to virus infections

text: Abstract Macrophages are thought to constitute an important element in the body's natural defense against invasion and dissemination of viruses. Possible antiviral mechanisms of macrophages are defined and referred to as intrinsic, i.e. the ability of macrophages to serve as a non-permissive barrier between the virus and susceptible cells and extrinsic, i.e. the ability of macrophages to affect the virus or virus replication in surrounding cells. Most studies on the role of macrophages in natural resistance to virus infections have been performed in animal models. An interesting aspect of many viral infections in animals is the finding of a genetically determined variation in natural resistance. Because of the availability of numerous inbred and congenic strains most studies on genetically determined resistance have been performed in mice. The classical examples are resistance to flaviviruses and susceptibility to mouse hepatitis virus, both of which are inherited as dominant, monogenic traits. With these viruses macrophage intrinsic restriction of virus replication has been found to express at the cellular level the genetics of resistance/susceptibility seen in the intact animal. Other examples, where macrophages have been implicated in genetically determined resistance include herpes simplex virus and influenza virus. The involvement of macrophages in natural resistance to these viruses is discussed in relation to other putative resistance determinants like interferon production and sensitivity and natural killer cell activity.


title: Diagnostic value of respiratory virus detection in symptomatic children using real-time PCR

text: BACKGROUND: Acute respiratory tract infections are an important public health problem. Sensitive and rapid diagnostic techniques have been developed and are used in daily clinical practice. Here we evaluate the clinical relevance of detecting 20 common respiratory pathogens by molecular methods in a general pediatric clinic. METHODS: Nasopharynx samples of children < 18 years of age with respiratory symptoms referred to a general pediatric clinic were tested for the presence of 19 viruses and Mycoplasma pneumoniae, using real-time polymerase chain reaction. RESULTS: Of 177 patients included in this retrospective study, 73% were positive for at least one virus. Respiratory syncytial virus (36.6%) and human rhinovirus (24%) were most frequently detected. Patients in whom a respiratory virus or Mycoplasma pneumoniae was detected, were younger (6 versus 24 months; p < 0.001) and more often hospitalized (116 versus 34; p = 0.001) than patients in whom no respiratory pathogen was detected. Also they were more likely to present with feeding problems, dyspnea, rhinorrhea and wheezing (all p < 0.05) than patients without a respiratory pathogen. In the majority of cases, clinicians did not change their antibiotic management after detecting a viral respiratory pathogen. No difference in mean Ct value was found between patients with one respiratory pathogen and those with >1 respiratory pathogen (30.5 versus 31.2; p = 0.573). CONCLUSION: Routine testing of common respiratory pathogens could lead to a better understanding of their role in disease in children with respiratory symptoms.


title: Structural basis for dimerization and RNA binding of avian infectious bronchitis virus nsp9

text: The potential for infection by coronaviruses (CoVs) has become a serious concern with the recent emergence of Middle East respiratory syndrome and severe acute respiratory syndrome (SARS) in the human population. CoVs encode two large polyproteins, which are then processed into 15–16 nonstructural proteins (nsps) that make significant contributions to viral replication and transcription by assembling the RNA replicase complex. Among them, nsp9 plays an essential role in viral replication by forming a homodimer that binds single‐stranded RNA. Thus, disrupting nsp9 dimerization is a potential anti‐CoV therapy. However, different nsp9 dimer forms have been reported for alpha‐ and beta‐CoVs, and no structural information is available for gamma‐CoVs. Here we determined the crystal structure of nsp9 from the avian infectious bronchitis virus (IBV), a representative gamma‐CoV that affects the economy of the poultry industry because it can infect domestic fowl. IBV nsp9 forms a homodimer via interactions across a hydrophobic interface, which consists of two parallel alpha helices near the carboxy terminus of the protein. The IBV nsp9 dimer resembles that of SARS‐CoV nsp9, indicating that this type of dimerization is conserved among all CoVs. This makes disruption of the dimeric interface an excellent strategy for developing anti‐CoV therapies. To facilitate this effort, we characterized the roles of six conserved residues on this interface using site‐directed mutagenesis and a multitude of biochemical and biophysical methods. We found that three residues are critical for nsp9 dimerization and its abitlity to bind RNA.


title: Tracheotomy in COVID‐19 patients: Optimizing patient selection and identifying prognostic indicators

text: BACKGROUND: Tracheotomy, through its ability to wean patients off ventilation, can shorten ICU length of stay and in doing so increase ICU bed capacity, crucial for saving lives during the COVID‐19 pandemic. To date, there is a paucity of patient selection criteria and prognosticators to facilitate decision making and enhance precious ICU capacity. METHODS: Prospective study of COVID‐19 patients undergoing tracheotomy (n = 12) over a 4‐week period (March‐April 2020). Association between preoperative and postoperative ventilation requirements and outcomes (ICU stay, time to decannulation, and death) were examined. RESULTS: Patients who sustained FiO(2) ≤ 50% and PEEP ≤ 8 cm H(2)O in the 24 hours pretracheotomy exhibited a favorable outcome. Those whose requirements remained below these thresholds post‐tracheotomy could be safely stepped down after 48 hours. CONCLUSION: Sustained FiO(2) ≤ 50% and PEEP ≤ 8 cm H(2)O in the 48 hours post‐tracheotomy are strong predictive factors for a good outcome, raising the potential for these patients to be stepped down early, thus increasing ICU capacity.


title: Porcine circovirus type 2 (PCV2) enteric disease: An independent condition or part of the systemic disease?

text: Abstract Intestinal disorders in growing and finishing pigs have been associated with several infectious agents, including Porcine circovirus type 2 (PCV2). This virus has been mainly related with PCV2-systemic disease (PCV2-SD); nevertheless, some authors have suggested a possible restricted intestinal infection of this virus associated with enteric clinical signs. This condition has been referred as PCV2-enteric disease (PCV2-ED). The present study analysed retrospectively, from a pathological point of view, the relation between intestinal disorders and PCV2 infection in nursery and growing-finishing pigs. Among the 96 selected pigs suffering from enteric disease and submitted for necropsy between 1998 and 2011, the most prevalent enteric lesions were catarrhal enteritis/colitis (77.1%), followed by fibrinous lesions (11.5%), granulomatous inflammation (4.2%) and other lesions such as haemorrhages or ulceration (4.2%). Seventy-two pigs (75%) were positive for PCV2 by in situ hybridization (ISH). Among positive pigs for PCV2 ISH, 39 animals suffered from PCV2-SD and 33 had no lymphoid lesions but low amount of viral nucleic acid in several lymphoid tissues, therefore, these animals did not qualify for PCVD-ED. In conclusion, all animals with enteric disorders that were positive to PCV2 by ISH had evidence of viral systemic infection. These results suggest that PCV2-ED is probably a negligible condition and PCV2 mainly contributes to enteric clinical disorders in relation to PCV2-SD occurrence.


title: STAT3 in Skeletal Muscle Function and Disorders

text: Signal transducer and activator of transcription 3 (STAT3) signaling plays critical roles in regulating skeletal muscle mass, repair, and diseases. In this review, we discuss the upstream activators of STAT3 in skeletal muscles, with a focus on interleukin 6 (IL6) and transforming growth factor beta 1 (TGF-β1). We will also discuss the double-edged effect of STAT3 activation in the muscles, including the role of STAT3 signaling in muscle hypertrophy induced by exercise training or muscle wasting in cachectic diseases and muscular dystrophies. STAT3 is a critical regulator of satellite cell self-renewal after muscle injury. STAT3 knock out affects satellite cell myogenic progression by impairing proliferation and inducing premature differentiation. Recent studies in STAT3 signaling demonstrated its direct role in controlling myogenic capacity of myoblasts and satellite cells, as well as the potential benefit in using STAT3 inhibitors to treat muscle diseases. However, prolonged STAT3 activation in muscles has been shown to be responsible for muscle wasting by activating protein degradation pathways. It is important to balance the extent of STAT3 activation and the duration and location (cell types) of the STAT3 signaling when developing therapeutic interventions. STAT3 signaling in other tissues and organs that can directly or indirectly affects skeletal muscle health are also discussed.


title: A structure-based rationale for sialic acid independent host-cell entry of Sosuga virus

text: The bat-borne paramyxovirus, Sosuga virus (SosV), is one of many paramyxoviruses recently identified and classified within the newly established genus Pararubulavirus, family Paramyxoviridae. The envelope surface of SosV presents a receptor-binding protein (RBP), SosV-RBP, which facilitates host-cell attachment and entry. Unlike closely related hemagglutinin neuraminidase RBPs from other genera of the Paramyxoviridae, SosV-RBP and other pararubulavirus RBPs lack many of the stringently conserved residues required for sialic acid recognition and hydrolysis. We determined the crystal structure of the globular head region of SosV-RBP, revealing that while the glycoprotein presents a classical paramyxoviral six-bladed β-propeller fold and structurally classifies in close proximity to paramyxoviral RBPs with hemagglutinin-neuraminidase (HN) functionality, it presents a receptor-binding face incongruent with sialic acid recognition. Hemadsorption and neuraminidase activity analysis confirms the limited capacity of SosV-RBP to interact with sialic acid in vitro and indicates that SosV-RBP undergoes a nonclassical route of host-cell entry. The close overall structural conservation of SosV-RBP with other classical HN RBPs supports a model by which pararubulaviruses only recently diverged from sialic acid binding functionality.


title: ACE2, a new regulator of the renin–angiotensin system

text: Abstract Angiotensin-converting enzyme (ACE) is a zinc metalloproteinase and a key regulator of the renin–angiotensin system (RAS). ACE2 is a newly described enzyme identified in rodents and humans with a more restricted distribution than ACE, and is found mainly in heart and kidney. ACE2 cleaves a single residue from angiotensin I (Ang I) to generate Ang 1–9, and degrades Ang II, the main effector of the RAS, to the vasodilator Ang 1–7. The importance of ACE2 in normal physiology and pathophysiological states is largely unknown. ACE2 might act in a counter-regulatory manner to ACE, modulating the balance between vasoconstrictors and vasodilators within the heart and kidney, and playing a significant role in regulating cardiovascular and renal function.


title: A metaanalysis of bat phylogenetics and positive selection based on genomes and transcriptomes from 18 species

text: Historically, the evolution of bats has been analyzed using a small number of genetic loci for many species or many genetic loci for a few species. Here we present a phylogeny of 18 bat species, each of which is represented in 1,107 orthologous gene alignments used to build the tree. We generated a transcriptome sequence of Hypsignathus monstrosus, the African hammer-headed bat, and additional transcriptome sequence for Rousettus aegyptiacus, the Egyptian fruit bat. We then combined these data with existing genomic and transcriptomic data from 16 other bat species. In the analysis of such datasets, there is no clear consensus on the most reliable computational methods for the curation of quality multiple sequence alignments since these public datasets represent multiple investigators and methods, including different source materials (chromosomal DNA or expressed RNA). Here we lay out a systematic analysis of parameters and produce an advanced pipeline for curating orthologous gene alignments from combined transcriptomic and genomic data, including a software package: the Mismatching Isoform eXon Remover (MIXR). Using this method, we created alignments of 11,677 bat genes, 1,107 of which contain orthologs from all 18 species. Using the orthologous gene alignments created, we assessed bat phylogeny and also performed a holistic analysis of positive selection acting in bat genomes. We found that 181 genes have been subject to positive natural selection. This list is dominated by genes involved in immune responses and genes involved in the production of collagens.


title: Viral etiology of pneumonia among severely malnourished under-five children in an urban hospital, Bangladesh

text: BACKGROUND: In Bangladesh, pneumonia has a higher mortality among malnourished children aged <5 years. Evaluating pneumonia etiology among malnourished children may help improve empiric treatment guidelines. METHODS: During April 2015—December 2017, we conducted a case-control study among severe acute malnourished (SAM) children aged <5 years admitted to the Dhaka hospital of International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b). We enrolled hospital admitted SAM children with clinical or radiological pneumonia as cases (during April 2015 to March 2017) and hospital admitted SAM children without any respiratory symptom in the past 10 days before admission as controls (during February 2016 to December 2017). We tested nasopharyngeal wash from both case and control for respiratory syncytial virus (RSV), human metapneumovirus (HMPV), influenza viruses, human parainfluenza viruses (HPIV), rhinovirus and adenovirus by singleplex real-time reverse transcriptase polymerase chain reaction. To identify the independent association of pneumonia with viral pathogens during February 2016 to March 2017, we used multivariable logistic regression for calculating adjusted odds ratios. RESULTS: We enrolled 360 cases and 334 controls. For case and control the median age was 8 months (IQR: 5–13) and 11 months (IQR: 6–18) (p = 0.001) respectively. Weight/age Z-score was -4.3 (SD ±0.7) for cases and -4.1 (SD ±1.1) for controls (p = 0.01). Among cases 68% had both clinical and radiological pneumonia, 1% had clinical pneumonia and 31% had only radiological pneumonia. Respiratory virus detection was high in cases compared to controls [69.9% (251) vs. 44.8% (148), p = 0.0001]. The most frequently detected viruses among cases were rhinoviruses (79, 22.0%) followed by RSV (32, 8.9%), adenovirus (23, 6.4%), HPIV (22, 6.1%), influenza virus (16, 4.5%), and HMPV (16, 4.5%). Among the controls, rhinoviruses (82, 24.8%) were most commonly detected one followed by adenovirus (26,7.9%), HMPV (5, 1.5%), HPIV (4, 1.2%), RSV (3, 0.9%), and influenza virus (2, 0.6%). RSV (OR 13.1; 95% CI: 1.6, 106.1), influenza virus (OR 8.7; 95% CI: 1.0, 78.9), HPIV (3.8; 95% CI: 1.0, 14.8), and HMPV (2.7; 95% CI: 1.3, 5.5) were independently associated with pneumonia while compared between 178 cases and 174 controls. CONCLUSION: Viral etiology of pneumonia in SAM children were mainly attributable to RSV, influenza, HPIV and HMPV. Our study findings may help in planning further studies targeting vaccines or drugs against common respiratory viruses responsible for pneumonia among SAM children.


title: The assessment of transmission efficiency and latent infection period on asymptomatic carriers of SARS-CoV-2 infection

text: ABSTRACT Few studies aimed on the transmission efficiency of asymptomatic carriers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A follow-up study was performed on 147 asymptomatic carriers in Anhui Province. Of 147 asymptomatic carriers, 50.0% were male, 50.3% cases were older than 40 years, and 43.8% were farmers, 68.7% cases were from north of Anhui Province. There were 16 asymptomatic carriers developed illness in the following 14 days isolated observation, and diagnosed as confirmed cases. The possible latent infection period was evaluated ranged from one to five days before onset, and the median time was two days. The second attack rate of 16 confirmed cases whom transferred from asymptomatic carriers was 9.7% (23/236), while 131 asymptomatic carriers caused 2.6% (24/914) close contacts infection, there was a significant difference of second attack rate among two groups (P＜0.001). Our study indicated that COVID-19 cases are contagious during the incubation period, and the close contact screening should be covered the incubation period. Furthermore, the transmission efficiency of asymptomatic carriers was lower than that of confirmed cases.


title: Guillain Barre syndrome associated with COVID-19 infection: A case report

text: Abstract Novel outbreak with coronavirus 2019 began since 31 December 2019. Coronaviruses can cause multiple systemic infections that respiratory complications are the most obvious symptoms. In this report, we describe the symptoms of Guillain Barre syndrome (GBS) in one infected patient with COVID-19, for the first time. We reported a 65-years- old male patient with complaints of acute progressive symmetric ascending quadriparesis. Two weeks prior to hospitalization, the patient suffered from cough, fever, and RT-PCR was reported positive for COVID-19 infection. The electrodiagnostic test showed that the patient is an AMSAN variant of GBS. COVID-19 stimulates inflammatory cells and produces various inflammatory cytokines and as a result, it creates immune-mediated processes. GBS is an immune-mediated disorder and molecular mimicry as a mechanism of autoimmune disorder plays an important role in creating it. It is unclear whether COVID-19 induces the production of antibodies against specific gangliosides. Further investigations should be conducted about the mechanism of GBS in patients with COVID-19, in the future.


title: Increased litter survival rates, reduced clinical illness and better lactogenic immunity against TGEV in gilts that were primed as neonates with porcine respiratory coronavirus (PRCV)

text: Abstract Establishing immunological memory in female piglets at a young age with PRCV was effective in inducing a secondary immune response to a limiting dose of virulent TGEV given orally 13–18 days prior to farrowing. Subsequently, because of passive antibody transfer, the offspring of these primed gilts were more efficient in surviving a lethal TGEV challenge. An average survival rate of 89% occurred in 6 litters of piglets from primed gilts that were boosted with 2.8×106 plaque forming units (PFU) of TGEV whereas 76% of the piglets survived in three litters that suckled primed gilts boosted with 3.0×105 PFU of TGEV. Non-primed gilts given identical pre-farrowing doses of TGEV had litter survival rates of 63 and 55%, respectively. Moreover, both groups of litters from primed gilts suffered less clinical illness (as measured by the extent of weight loss post-challenge) than control litters. Priming of the piglets as neonates and boosting the pregnant gilts produced an anamnestic systemic immune response and correspondingly higher milk titers in the primed gilts compared to control animals. Thus, priming piglets with PRCV was beneficial in providing resistance to TGEV and could be incorporated into a vaccine strategy that yields better protection against TGEV.


title: Infectious disease symptoms and microbial carriage among French medical students travelling abroad: A prospective study

text: Abstract Background In France, no previous studies have focused specifically on health problems among medical students during internships abroad including the clinical symptoms suggestive of infectious diseases and the acquisition of pathogen carriage. Methods Clinical follow up and qPCR based respiratory, gastrointestinal and vaginal pathogen carriage before and after travel were prospectively assessed in a cohort of medical students departing from Marseille, France. Results 134 students were included. 73.9%, 38.8% and 5.0% of students reported gastrointestinal, respiratory and vaginal symptoms, respectively. The acquisition rate of Enteroaggregative Escherichia coli (EAEC) and Enteropathogenic E. coli (EPEC) was 53% and 41%, respectively. The acquisition of respiratory viruses was low but associated with persisting symptoms, while bacterial acquisition ranged from 3.3% for Streptococcus pyogenes to 15.0% for Haemophilus influenzae. Gardnerella vaginalis and Atopobium vaginae acquisition rates were 7.7% and 14.3% respectively. Five students (5.1%) had molecular quantification criteria for bacterial vaginosis on return. Conclusion This preliminary study demonstrates that besides the known risk of gastrointestinal and respiratory infections and associated changes in intestinal and respiratory microbiota, medical students abroad may also experience changes in vaginal microbiota leading, in some cases, to clinical symptoms or the acquisition of bacterial vaginosis, which may be asymptomatic.


title: Impact of SARS-CoV-2 infection on neurodegenerative and neuropsychiatric diseases: A delayed pandemic?

text: Abstract Introduction SARS-CoV-2 was first detected in December 2019 in the Chinese city of Wuhan and has since spread across the world. At present, the virus has infected over 1.7 million people and caused over 100000 deaths worldwide. Research is currently focused on understanding the acute infection and developing effective treatment strategies. In view of the magnitude of the epidemic, we conducted a speculative review of possible medium- and long-term neurological consequences of SARS-CoV-2 infection, with particular emphasis on neurodegenerative and neuropsychiatric diseases of neuroinflammatory origin, based on the available evidence on neurological symptoms of acute SARS-CoV-2 infection. Development We systematically reviewed the available evidence about the pathogenic mechanisms of SARS-CoV-2 infection, the immediate and lasting effects of the cytokine storm on the central nervous system, and the consequences of neuroinflammation for the central nervous system. Conclusions SARS-CoV-2 is a neuroinvasive virus capable of triggering a cytokine storm, with persistent effects in specific populations. Although our hypothesis is highly speculative, the impact of SARS-CoV-2 infection on the onset and progression of neurodegenerative and neuropsychiatric diseases of neuroinflammatory origin should be regarded as the potential cause of a delayed pandemic that may have a major public health impact in the medium to long term. Cognitive and neuropsychological function should be closely monitored in COVID-19 survivors.


title: SARS‐CoV‐2 and Oral Ulcers; a Causative Agent or a Predisposing Factor?

text: Earlier reports on COVID‐19 have reported certain orofacial manifestations like taste loss and salivary gland infection (Dar‐Odeh et al, 2020). More recently, two studies from Spain and France reported oral ulcerative lesions in COVID‐19 patients ( Chaux‐Bodard et al, 2020; Carreras‐ Presas et al, 2020). The study from Spain included three patients. The first two cases (males) were suspected cases of COVID‐19 as testing was not done for them. Intraorally, they had oral ulcers affecting the hard palate unilaterally in the anatomic area innervated by greater palatine nerve.


title: Time for a Change: Personal Experiences With COVID-19 and Diabetes

text: Personal experiences during the COVID-19 pandemic.


title: The Host Restriction Factor Interferon-Inducible Transmembrane Protein 3 Inhibits Vaccinia Virus Infection

text: Interferons (IFNs) establish dynamic host defense mechanisms by inducing various IFN-stimulated genes that encodes many antiviral innate immune effectors. IFN-inducible transmembrane (IFITM) proteins have been identified as intrinsic antiviral effectors, which block the entry of a broad spectrum of enveloped RNA viruses by interrupting virus-endosomal fusion. However, antiviral activity of IFITM proteins against mammalian DNA virus has not been demonstrated till date. Here, we sought to investigate the antiviral activities and mechanisms of interferon-inducible transmembrane protein 3 (IFITM3) protein against poxvirus infection. Analysis of expression kinetics of cell endogenous IFITM3 protein indicated that vaccinia virus (VACV) infection suppressed its translation, which was independent of IRF3 phosphorylation triggered by VACV. Although silencing of endogenous IFITM proteins did not affect their baseline antiviral effects in the cell, it has reduced the IFN-α-mediated inhibition of VACV infection, and also modulated VACV-induced cell death. Moreover, we discovered that overexpression of IFITM3 significantly restricted VACV infection, replication and proliferation mainly by interfering with virus entry processes prior to the virus nucleocapsid entry into the cytoplasm. Interestingly, IFITM3 overexpression showed an impact on virus binding. Furthermore, IFITM3 interfered with the cytosolic entry of virus through low pH-dependent fashion. Taken together, our findings provide the first evidence of exogenously expressed IFITM3 protein restricting infection of an enveloped DNA virus, thus expanding their antiviral spectrum. This study further explores the complex mechanism and provides novel insights into the interaction between virus infection and host defense.


From Fear to Fortitude: Using the Power Within the Nursing Profession to Fight COVID-19


title: Investigation of an experimental infection model of equine coronavirus in adult horses

text: BACKGROUND: Equine coronavirus (ECoV) is a recently reported enteric disease of adult horses. Natural infection by ECoV has been reported in adult horses worldwide, whereas experimental infection has only been reported in juvenile horses. An experimental infection model is needed to study the clinical presentation, laboratory abnormalities, and pathophysiological changes associated with ECoV. OBJECTIVES: To investigate the clinical, hematologic, molecular, and serological features of adult horses experimentally infected with ECoV. ANIMALS: Eight adult horses. METHODS: Four horses were intragastrically infected with fecal material containing 10(9) genome equivalents of ECoV. Four additional horses were exposed daily to the feces from the experimentally‐infected horses. Monitoring included physical examinations, as well as daily nasal swab, whole blood, and fecal collection for molecular detection of ECoV. Blood was collected every other day for hematologic analysis and weekly for serologic analysis. RESULTS: All 8 horses shed ECoV in feces. Six of the 8 horses (75%) exhibited mild, clinical disease with soft, formed manure; 1 horse exhibited transient pyrexia. All horses maintained total white cell counts within normal limits, but 3 horses developed transient lymphopenia. No statistically significant differences (P = .20) were observed in quantity of fecal shedding of ECoV between the 2 groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Experimental infection of adult horses with ECoV was associated with mild and self‐limiting clinical signs, transient lymphopenia, and fecal shedding of ECoV, which mimics natural infection. No differences between experimentally‐infected horses and horses exposed to ECoV‐containing feces were identified. Results of our study support a fecal‐oral route of transmission.


title: From the Argonauts Mythological Sailors to the Argonautes RNA-Silencing Navigators: Their Emerging Roles in Human-Cell Pathologies

text: Regulation of gene expression has emerged as a fundamental element of transcript homeostasis. Key effectors in this process are the Argonautes (AGOs), highly specialized RNA-binding proteins (RBPs) that form complexes, such as the RNA-Induced Silencing Complex (RISC). AGOs dictate post-transcriptional gene-silencing by directly loading small RNAs and repressing their mRNA targets through small RNA-sequence complementarity. The four human highly-conserved family-members (AGO1, AGO2, AGO3, and AGO4) demonstrate multi-faceted and versatile roles in transcriptome’s stability, plasticity, and functionality. The post-translational modifications of AGOs in critical amino acid residues, the nucleotide polymorphisms and mutations, and the deregulation of expression and interactions are tightly associated with aberrant activities, which are observed in a wide spectrum of pathologies. Through constantly accumulating information, the AGOs’ fundamental engagement in multiple human diseases has recently emerged. The present review examines new insights into AGO-driven pathology and AGO-deregulation patterns in a variety of diseases such as in viral infections and propagations, autoimmune diseases, cancers, metabolic deficiencies, neuronal disorders, and human infertility. Altogether, AGO seems to be a crucial contributor to pathogenesis and its targeting may serve as a novel and powerful therapeutic tool for the successful management of diverse human diseases in the clinic.


title: Rapid report: Early demand, profiles and concerns of mental health users during the coronavirus (COVID-19) pandemic

text: BACKGROUND: Trends in contact with a high volume national digital mental health service (DMHS), the MindSpot Clinic, provide a unique opportunity to assess the mental health effects of the COVID-19 pandemic. METHODS: Three methods were used to assess changes in responses to COVID-19. First, website visits and call centre traffic were compared across two time periods: the “comparison period” (1 September 2020 to 28 September 2019), and during the early weeks of the “COVID-19 pandemic” (19 March 2020 to 15 April 2020). Second, demographic and symptom data were compared across all patients who started an assessment during the comparison (n = 1650) and the COVID-19 period (n = 1668). Third, responses to questions about the impact of COVID-19 introduced to the assessment from 19 March 2020, and reports from treating therapists were examined. RESULTS: There was an 89% increase in website visits and a 90% increase in telephone calls to the clinic in the early COVID-19 period compared to the comparison period. There was a higher proportion of females in the COVID-19 sample (76.9% vs. 72.9), and a lower proportion reported being in employment (52.8% vs. 60.8%). There was a small but significant increase in the severity of anxiety symptoms, and an increase in the number of people reporting recent onset of anxiety and depression. However, there were no differences between groups in severity of symptoms of distress or depression. Most people (94%) reported concern about the impact of COVID-19, and 88% reported making changes in lifestyle. Older adults had higher levels of concern about COVID-19. Therapists reported that patients were concerned about how to access testing, manage quarantine, financial security and the effect of social isolation. CONCLUSIONS: COVID-19 has resulted in a significant increase in contact with an established DMHS, but we have not yet detected increases in baseline symptom severity. With the prospect of prolonged restriction of movement, DMHS such as MindSpot could play an important role in both providing clinical services and monitoring the mental health of the population.


title: Antigenic structures stably expressed by recombinant TGEV-derived vectors

text: Abstract Coronaviruses (CoVs) are positive-stranded RNA viruses with potential as immunization vectors, expressing high levels of heterologous genes and eliciting both secretory and systemic immune responses. Nevertheless, its high recombination rate may result in the loss of the full-length foreign gene, limiting their use as vectors. Transmissible gastroenteritis virus (TGEV) was engineered to express porcine reproductive and respiratory syndrome virus (PRRSV) small protein domains, as a strategy to improve heterologous gene stability. After serial passage in tissue cultures, stable expression of small PRRSV protein antigenic domains was achieved. Therefore, size reduction of the heterologous genes inserted in CoV-derived vectors led to the stable expression of antigenic domains. Immunization of piglets with these TGEV vectors led to partial protection against a challenge with a virulent PRRSV strain, as immunized animals showed reduced clinical signs and lung damage. Further improvement of TGEV-derived vectors will require the engineering of vectors with decreased recombination rate.


50th Anniversary Editorial: Building on firm foundations


title: Applications of RNA interference: current state and prospects for siRNA-based strategies in vivo

text: Within the recent years, RNA interference (RNAi) has become an almost-standard method for in vitro knockdown of any target gene of interest. Now, one major focus is to further explore its potential in vivo, including the development of novel therapeutic strategies. From the mechanism, it becomes clear that small interfering RNAs (siRNAs) play a pivotal role in triggering RNAi. Thus, the efficient delivery of target gene-specific siRNAs is one major challenge in the establishment of therapeutic RNAi. Numerous studies, based on different modes of administration and various siRNA formulations and/or modifications, have already accumulated promising results. This applies to various animal models covering viral infections, cancer and multiple other diseases. Continuing efforts will lead to the development of efficient and “double-specific” drugs, comprising of siRNAs with high target gene specificity and of nanoparticles enhancing siRNA delivery and target organ specificity.


title: Ebola virus disease: How can African pharmacists respond to future outbreaks?

text: Abstract In its forty years history (1976–2016), the West African region has recorded the most devastating form of the Ebola virus disease. The sparse knowledge of healthcare professionals and general public combined with lesser responses from international community are major factors for the dissemination of the disease. In the context of this outbreak, there is a need to highlight the roles and responsibilities of pharmacists, especially in the African healthcare setting. Moreover, the prerequisite of diagnostic kits for the timely detection of the infection as well as pharmacists' awareness of the current therapeutic regimen are recommended.


title: Near-infrared observations of active asteroid (3200) Phaethon reveal no evidence for hydration

text: Asteroid (3200) Phaethon is an active near-Earth asteroid and the parent body of the Geminid Meteor Shower. Because of its small perihelion distance, Phaethon's surface reaches temperatures sufficient to destabilize hydrated materials. We conducted rotationally resolved spectroscopic observations of this asteroid, mostly covering the northern hemisphere and the equatorial region, beyond 2.5-micron to search for evidence of hydration on its surface. Here we show that the observed part of Phaethon does not exhibit the 3-micron hydrated mineral absorption (within 2-sigma). These observations suggest that Phaethon's modern activity is not due to volatile sublimation or devolatilization of phyllosilicates on its surface. It is possible that the observed part of Phaethon was originally hydrated and has since lost volatiles from its surface via dehydration, supporting its connection to the Pallas family, or it was formed from anhydrous material.


title: The interaction of the SARS coronavirus non-structural protein 10 with the cellular oxido-reductase system causes an extensive cytopathic effect

text: Abstract The pathological mechanism of SARS-CoV infection was investigated. The gene for the SARS-CoV non-structural protein 10, which is located in the open reading frame of pp1a/pp1ab gene, was synthesized and used to screen for the specific cellular gene coding for the protein interacting with this nsp10 protein in a human embryo lung cDNA library using a yeast trap method. The results indicated that apart from the two subunits of cellular RNA polymerase complex, BTF3 and ATF5, this nsp10 protein was also able to interact specifically with the NADH 4L subunit and cytochrome oxidase II. Further study revealed that the activity of the NADH-cytochrome was altered and the inner mitochondrial membrane was depolarized in the transfected human embryo lung fibroblast by the nsp10 protein gene. The cytopathic effect of the Coronavirus 229E strain appeared more extensive in these cells than in the control cells.


title: Synthetic virus-like particles prepared via protein corona formation enable effective vaccination in an avian model of coronavirus infection

text: Abstract The ongoing battle against current and rising viral infectious threats has prompted increasing effort in the development of vaccine technology. A major thrust in vaccine research focuses on developing formulations with virus-like features towards enhancing antigen presentation and immune processing. Herein, a facile approach to formulate synthetic virus-like particles (sVLPs) is demonstrated by exploiting the phenomenon of protein corona formation induced by the high-energy surfaces of synthetic nanoparticles. Using an avian coronavirus spike protein as a model antigen, sVLPs were prepared by incubating 100 nm gold nanoparticles in a solution containing an optimized concentration of viral proteins. Following removal of free proteins, antigen-laden particles were recovered and showed morphological semblance to natural viral particles under nanoparticle tracking analysis and transmission electron microscopy. As compared to inoculation with free proteins, vaccination with the sVLPs showed enhanced lymphatic antigen delivery, stronger antibody titers, increased splenic T-cell response, and reduced infection-associated symptoms in an avian model of coronavirus infection. Comparison to a commercial whole inactivated virus vaccine also showed evidence of superior antiviral protection by the sVLPs. The study demonstrates a simple yet robust method in bridging viral antigens with synthetic nanoparticles for improved vaccine application; it has practical implications in the management of human viral infections as well as in animal agriculture.


title: The intensive care unit work environment: Current challenges and recommendations for the future

text: Abstract The need for critical care services has grown substantially in the last decade in most of the G8 nations. This increasing demand has accentuated an already existing shortage of trained critical care professionals. Recent studies argue that difficulty in recruiting an appropriate workforce relates to a shortage of graduating professionals and unhealthy work environments in which critical care professionals must work. Objective This narrative review summarizes existing literature and experiences about the key work environment challenges reported within the critical care context and suggests best practices—implemented in hospitals or suggested by professional associations—which can be an initial step in enhancing patient care and professional recruitment and retention in our intensive care units, with particular emphasis on the recruitment and retention of an appropriately trained and satisfied workforce. The experiences are categorized for the physical, emotional, and professional environments. A case study is appended to enhance understanding of the magnitude and some of the proposed remedies of these experiences.


title: UPDATE ON ACUTE MYOCARDITIS

text: Acute myocarditis (AM), a recent-onset inflammation of the heart, has heterogeneous clinical presentations, varying from minor symptoms to high-risk cardiac conditions with severe heart failure, refractory arrhythmias, and cardiogenic shock. AM is moving from being a definitive diagnosis based on histological evidence of inflammatory infiltrates on cardiac tissue to a working diagnosis supported by high sensitivity troponin increase in association with specific cardiac magnetic resonance imaging (CMRI) findings. Though experts still diverge between those advocating for histological definition versus those supporting a mainly clinical definition of myocarditis, in the real-world practice the diagnosis of AM has undoubtedly shifted from being mainly biopsy-based to solely CMRI-based in most of clinical scenarios. It is thus important to clearly define selected settings where EMB is a must, as information derived from histology is essential for an optimal management. As in other medical conditions, a risk-based approach should be promoted in order to identify the most severe AM cases requiring appropriate bundles of care, including early recognition, transfer to tertiary centers, aggressive circulatory supports with inotropes and mechanical devices, histologic confirmation and eventual immunosuppressive therapy. Despite improvements in recognition and treatment of AM, including a broader use of promising mechanical circulatory supports, severe forms of AM are still burdened by dismal outcomes. This review is focused on recent clinical studies and registries that shed new insights on AM. Attention will be paid to contemporary outcomes and predictors of prognosis, the emerging entity of immune checkpoint inhibitors-associated myocarditis, updated CMRI diagnostic criteria, new data on the use of temporary mechanical circulatory supports in fulminant myocarditis. The role of viruses as etiologic agents will be reviewed and a brief update on pediatric AM is also provided. Finally, we summarize a risk-based approach to AM, based on available evidence and clinical experience.


title: Antioxidant Status and Immune Activity of Glycyrrhizin in Allergic Rhinitis Mice

text: Oxidative stress is considered as a major risk factor that contributes to increased lipid peroxidation and declined antioxidants in some degenerative diseases. Glycyrrhizin is widely used to cure allergic diseases due to its medicinal properties. In the present study, we evaluated the role of glycyrrhizin on lipid peroxidation and antioxidant status in the blood and nasal mucosa of allergic rhinitis (AR) mice. Mice were divided into six groups: normal control mice, model control (MC) mice, three glycyrrhizin-treated mice groups and lycopene-treated mice. Sensitization-associated increase in lipid peroxidation was observed in the blood and nasal mucosa of MC mice. Activities of antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), total antioxidant capacity (TAOC) and levels of glutathione (GSH) were found to be significantly decreased in the blood and nasal mucosa in MC mice when compared to normal control mice. However, normalized lipid peroxidation and antioxidant defenses were reported in the glycyrrhizin-treated and lycopene-treated mice. Moreover, glycyrrhizin treatment still enhanced IFN-γ and reduced IL-4 levels in glycyrrhizin-treated mice. These findings demonstrated that glycyrrhizin treatment enhanced the antioxidant status and decreased the incidence of free radical-induced lipid peroxidation and improved immunity activities in the blood and nasal mucosa of AR mice.


title: Epidemiologic Features of 135 Patients With Coronavirus Disease (COVID-19) in Tianjin, China

text: OBJECTIVE: This study describes the epidemiologic features of an outbreak of the coronavirus disease (COVID-19) in Tianjin caused by a novel coronavirus and provides the scientific basis for prevention and control measures. METHODS: Data from COVID-19 cases were collected from daily notifications given to the National Health Commission of the People’s Republic of China and Tianjin Health Committee. All of the data were analyzed with SPSS, version 24.0 software (IBM Corp, Armonk, NY). RESULTS: As of February 24, 2020, there have been 135 confirmed cases, 3 deaths, and 87 recoveries in Tianjin, China. The incidence of COVID-19 was 8.65/1 000 000 with a 2.22% case fatality rate. Regarding geographic distribution, the incidence was 8.82 per 1 000 000 in urban areas and 8.00 per 1 000 000 in suburbs. During the early stage of the epidemic, most cases came from urban areas and in patients with a history of sojourning in Hubei Province. The majority of patients were 31–70 years old (75.97%). A familial clustering was the most important characteristic of COVID-19 (accounting for 74.81%). CONCLUSIONS: Current information suggests that people are generally susceptible to COVID-19, which has shown a familial clustering in Tianjin.


Managing Endovascular Workload During COVID-19 Outbreak – the Singapore Experience


title: Clinicopathological findings and disease staging of feline infectious peritonitis: 51 cases from 2003 to 2009 in Taiwan

text: Fifty-one cats histopathologically confirmed to have been naturally infected by feline infectious peritonitis (FIP), were collected to analyse the clinical and laboratory findings and to characterise disease staging. Effusive FIP was found in 33 cats, non-effusive FIP in 12 cats, and mixed-type in six cats. Highly significant decreases in haematocrit and albumin levels and an increase in total bilirubin level were noted in both effusive and non-effusive FIP, at first presentation and before death. In serial blood examinations of the effusive group, anaemia and increases in bilirubin and aspartate aminotransferase (AST) were observed from 2 weeks to 0–3 days before death. The packed cell volume, bilirubin, AST, potassium, and sodium levels were established to predict disease staging and survival time. Cumulative points ranging from 0 to 4, 5 to 11 and excess of 12, indicate that the cat can survive for at least 2 weeks, less than 2 weeks and less than 3 days, respectively.


title: Emergence of human caliciviruses among diarrhea cases in southwest China

text: BACKGROUND: Acute diarrhea is one of the most serious problems in global public health that causes considerable morbidity and mortality worldwide. Human caliciviruses (HuCV) including norovirus (NoV, genogroup GI and GII) and sapovirus (SaV), is a leading cause of acute sporadic diarrhea in individuals across all age groups. However, few studies had been conducted clarifying the characteristics of HuCV in diarrhea cases across all age groups in China. Our study was aimed at assessing the HuCV-related diarrhea burden and NoV genotypes distribution in southwest China. METHODS: The study was conducted in four hospitals in Kunming city, Yunnan province, from June 2014 to July 2015. Stool specimens were collected from 1,121 diarrhea cases and 319 healthy controls in outpatient departments. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect NoV (GI, GII) and SaV. Sequencing was applied to confirm the three viral infections and phylogenetic analysis was performed to determine their genotypes. A structured questionnaire was used to record the demographic information and clinical symptoms of subjects. RESULTS: HuCV was detected at an 11.0 % infection rate in 1,121 diarrhea cases and at 3.4 % rate in 319 non-diarrhea subjects (p < 0.0001, OR = 3.5, 95 % CI 1.8–6.5). The prevalence of the NoV genogroup GII and genotype GII.4 in diarrhea cases was significantly higher than that found in healthy controls (p < 0.0001, p = 0.018, respectively). NoV GII (n = 118, 10.5 %) was the most common HuCV subtype in diarrhea cases, followed by SaV (n = 3, 0.3 %) and NoV GI (n = 2, 0.2 %). Of 118 NoV GII strains isolated from diarrhea patients. GII.4 (n = 55, 46.6 %) was the predominant strain, followed by GII.3 (n = 28, 23.7 %), GII.12 (n = 25, 21.2 %), GII.17 (n = 8, 6.8 %), and GII.5 (n = 2, 1.7 %). Of the 55 GII.4 strains, the GII.4 Sydney 2012 variant had absolutely predominant prevalence (n = 52, 94.5 %), followed by the NoV GII.4-2006b variant (n = 3, 5.5 %). The GII.4 Orleans 2009 variant was not found in diarrhea cases of the study. CONCLUSIONS: NoV GII was the major genogroup and GII.4 was the most predominant strain detected in diarrhea patients. The GII.17 is an emergent variant in sporadic diarrhea and might become the predominant strain in diarrhea cases in the near future. Rapid, accurate detection kits need to be developed to help us find and treat NoV-associated diarrhea in clinical settings in a timely manner.


title: COVID-19 Pandemic: Global Impact and Potential Implications for Cardiovascular Disease in Canada

text: BACKGROUND: Literature indicates that cardiovascular disease (CVD, including stroke), older age, and availability of healthcare resources impact COVID-19 case fatality rates (CFR). The cumulative effect of COVID-19 CFR in global CVD populations and the extrapolated impact on access to healthcare services in the CVD population in Canada are not fully known. This study explored the relationships of factors that may impact COVID-19 CFR and estimated the potential indirect impact of COVID-19 on Canadian healthcare resources. METHODS: Country-level epidemiological data were analyzed to study the correlation, main effect, and interaction between COVID-19 CFR and: a) proportion of the population with CVD, b) proportion of the population ≥ 65 years, and c) availability of essential health services as defined by the World Health Organization Universal Health Coverage (UHC) index. For indirect implications on healthcare resources, estimates of the volume of postponed coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI) and valve surgeries in Ontario were calculated. RESULTS: Positive correlations were found between COVID-19 CFR and a) proportion of the population with CVD (ρ=0.40, p=0.001), b) proportion of the population ≥ 65 years (ρ=0.43, p=0.0005) and c) UHC index (ρ=0.27, p=0.03). For every 1% increase in proportion of the population ≥ 65 years or proportion of the population with CVD, COVID-19 CFR was 9% and 19% higher, respectively. Approximately 1,252 procedures would be postponed monthly in Ontario due to current public health measures. CONCLUSIONS: Countries with more prevalent CVD reported higher COVID-19 CFR. Strain on healthcare resources is likely in Canada.


title: Levels and sources of hourly PM2.5-related elements during the control period of the COVID-19 pandemic at a rural site between Beijing and Tianjin

text: Abstract To control the spread of the novel coronavirus disease 2019 (COVID-19) in China, many anthropogenic activities were reduced and even closed on the national scale. To study the impact of this reduction and closing down, hourly concentrations of PM2.5-related elements were measured at a rural site before (12–25 January 2020), during (26 January–9 February 2020) and after (22 March–2 April 2020) all people gathered in their homes and could not return to economic zones for work. Nine major sources were identified by the positive matrix factorization model, including fireworks burning, coal combustion, vehicle emissions, dust, Cr industry, oil combustion, Se industry, Zn smelter, and iron and steel industry. Before the control period, K, Fe, Ca, Zn, Ba and Cu were the main elements, and fireworks burning, Zn smelter and vehicle emissions provide the highest contributions to the total element mass with 55%, 12.1% and 10.3%, respectively. During the control period, K, Fe, Ba, Cu and Zn were the dominating elements, and fireworks burning and vehicle emissions contributed 55% and 27% of the total element mass. After the control period, Fe, K, Ca, Zn and Ba were the main elements, and dust and iron and steel industry were responsible for 56% and 21% of the total element mass. The increased contribution from vehicle emissions during the control period could be attributed to our sampling site being near a town hospital and the fact that the vehicle activities were not restricted. The source apportionment results were also related to air mass backward trajectories. The largest reductions of dust, coal combustion, and the industrial sources (Cr industry, Zn smelter, Se industry, iron and steel industry) were distinctly seen for northwest transport (Ulanqab) and were least significant for northeast transport (Tangshan and Tianjin).


title: High-neurovirulence GDVII virus induces apoptosis in murine astrocytes through tumor necrosis factor (TNF)-receptor and TNF-related apoptosis-inducing ligand

text: Abstract We carried out a study to determine if the high-neurovirulence GDVII strain of Theiler’s murine encephalomyelitis virus (TMEV) and the demyelinating, low-neurovirulence BeAn strain induced apoptosis in murine astrocytes. Astrocytes, the major glial cell population of the central nervous system, were semipermissive for GDVII virus replication. Programmed cell death, demonstrated by apoptosis-specific caspase-3 protease activity, was maximal 8 h after GDVII infection at an m.o.i. of 1. Purified TMEV capsid proteins VP1, VP2, and VP3 did not induce apoptosis but antibodies to VP1 and VP2 inhibited it. Antibody inhibition of caspase-3 activity as well as flow cytometry experiments implicated TNF-related apoptosis-inducing ligand (TRAIL) and TNF-α-receptor (TNF-R) in apoptosis signaling. Converselly, TNF-α and the TRAIL-receptor were not upregulated. Furthermore, the number of functional TNF-α receptors, but not their affinity, was increased in apoptotic GDVII virus-infected astrocytes, as confirmed in binding experiments with 125I-labeled recombinant murine TNF-α. In vivo studies showed that most of the cells loaded with the virus when injected in the brains of SJL mice were neurons but very few showed TUNEL costaining. Conversely, many of the apoptotic cells found were also positive for GFAP staining.