title: Ensuring the Biologic Safety of Plasma-Derived Therapeutic Proteins: Detection, Inactivation, and Removal of Pathogens

text: Human plasma-derived proteins, such as immunoglobulins, coagulation factors, α(1)-antitrypsin, fibrin sealants, and albumin, are widely used as therapeutics for many serious and life-threatening medical conditions. The human origin of these proteins ensures excellent efficacy and compatibility but may also introduce the risk of unintentional disease transmission. Historically, only viruses, particularly hepatitis and HIV, have posed serious threats to the safety of these therapeutics. Fortunately, between 1970 and 1990, the molecular biology of each of the major viruses was elucidated. These advances led to the development and implementation of effective donor screening tests, mainly based on immunoassays and nucleic acid testing, which resulted in a significant reduction of disease transmission risk. In addition, viral inactivation and removal steps were implemented and validated by manufacturers, further reducing the risk associated with known, as well as unidentified, viruses. Since the late 1990s, a different class of transmissible agent, referred to as prions, has been identified as a new risk for disease transmission. However, prion diseases are very rare, and prion transmission through plasma-derived proteins has not been reported to date. The prion-related risk is minimized by deferring donors with certain key risk factors, and by the manufacturing processes that are capable of removing prions. Advances in science and pathogen safety-related technology, compliance with good manufacturing practices by manufacturers, and increasingly stringent regulatory oversight, has meant that plasma-derived proteins have been developed into today’s highly effective therapeutics with very low risk of disease transmission.


title: Clinical predictors of chest radiographic abnormalities in young children hospitalized with bronchiolitis: a single center study

text: PURPOSE: Chest radiography is often performed on patients hospitalized with typical clinical manifestations of bronchiolitis. We aimed to determine the proportion of subjects with pathologic chest radiographic findings and the clinical predictors associated with pathologic chest radiographic findings in young children admitted with the typical presentation of bronchiolitis. METHODS: We obtained the following data at admission: sex, age, neonatal history, past history of hospitalization for respiratory illnesses, heart rate, respiratory rate, the presence of fever, total duration of fever, oxygen saturation, laboratory parameters (i.e., complete blood cell count, high-sensitivity C-reactive protein [hs-CRP], etc.), and chest radiography. RESULTS: The study comprised 279 young children. Of these, 26 had a chest radiograph revealing opacity (n=24) or atelectasis (n=2). Multivariate logistic regression analysis showed that after adjustment for confounding factors, the clinical predictors associated with pathologic chest radiographic findings in young children admitted with bronchiolitis were elevated hs-CRP level (>0.3 mg/dL) and past history of hospitalization for respiratory illnesses (all P<0.05). CONCLUSION: The current study suggests that chest radiographs in young children with typical clinical manifestations of bronchiolitis have limited value. Nonetheless, young children with clinical factors such as high hs-CRP levels at admission or past history of hospitalization for respiratory illnesses may be more likely to have pathologic chest radiographic findings.


title: Seasonality and selective trends in viral acute respiratory tract infections

text: Abstract Influenza A and B, and many unrelated viruses including rhinovirus, RSV, adenovirus, metapneumovirus and coronavirus share the same seasonality, since these viral acute respiratory tract infections (vARIs) are much more common in winter than summer. Unfortunately, early investigations that used recycled “pedigree” virus strains seem to have led microbiologists to dismiss the common folk belief that vARIs often follow chilling. Today, incontrovertible evidence shows that ambient temperature dips and host chilling increase the incidence and severity of vARIs. This review considers four possible mechanisms, M1 - 4, that can explain this link: (M1) increased crowding in winter may enhance viral transmission; (M2) lower temperatures may increase the stability of virions outside the body; (M3) chilling may increase host susceptibility; (M4) lower temperatures or host chilling may activate dormant virions. There is little evidence for M1 or M2, which are incompatible with tropical observations. Epidemiological anomalies such as the repeated simultaneous arrival of vARIs over wide geographical areas, the rapid cessation of influenza epidemics, and the low attack rate of influenza within families are compatible with M4, but not M3 (in its simple form). M4 seems to be the main driver of seasonality, but M3 may also play an important role.


title: Vaccination against enteric rota and coronaviruses in cattle and pigs: Enhancement of lactogenic immunity

text: Passive immunity against enteric viral infections is dependent upon the continual presence in the gut lumen of a protective level of specific antibodies. This article examines methods currently used to enhance the titre and duration of specific antibody in the mammary secretions of cows and pigs with particular reference to rotavirus and coronavirus infections. In addition, some of the potential problems to be found in attempting to produce vaccines against these viral infections are outlined


title: Point-of-care testing for respiratory viruses in adults: The current landscape and future potential

text: Summary Respiratory viruses are responsible for a large proportion of acute respiratory illness in adults as well as children, and are associated with a huge socio-economic burden worldwide. Development of accurate point-of-care tests (POCT) for respiratory viruses has been listed as a priority by the World Health Organisation and replacing the current paradigm of empirical antimicrobial use with directed use is a listed goal of the movement for reduction in antimicrobial resistance. POCTs for respiratory viruses have previously been limited by the poor sensitivity of antigen detection based tests and by a limited range of detectable viruses. Highly accurate molecular platforms are now able to test for a comprehensive range of viruses, can be operated by non-laboratory staff and can generate a result in approximately 1 h, making them potentially deployable as POCTs. The potential clinical benefits of POC testing for respiratory viruses in adults include a reduction in unnecessary antibiotic use, improved antiviral prescribing for influenza and rationalisation of isolation facilities. We review here the burden of disease, the currently available molecular platforms with potential for POCT use and the existing evidence for clinical and economic benefits of testing for respiratory viruses in adults.


title: Incidence of novel coronavirus (2019-nCoV) infection among people under home quarantine in Shenzhen, China

text: Since the outbreak of 2019-nCoV in December, Chinese government has implemented various measures including travel bans, centralized treatments, and home quarantines to slowing the transmission across the country. In this study, we aimed to estimate the incidence of 2019-nCoV infection among people under home quarantine in Shenzhen, China. Methods: We used a stratified multistage random sampling method to recruit participants and collected demographic information and laboratory results of people under home quarantine. We conducted descriptive analysis to estimate the basic characteristics and to calculate the incidence in out study population. Results: A total of 2004 people under home quarantine participated in this study, of which 1637 participants finished the questionnaire with a response rate of 81.7%. Mean age of the participants was 33.7 years, ranging from 0.3 to 80.2 years. Of people who provided clear travel history, 129 people have traveled to Wuhan city and 1,046 people have traveled to other cities in Hubei province within 14 days before the home quarantine. Few (less than 1%) participants reported contact history with confirmed or suspected cases during their trip and most of these arrived at Shenzhen between Jan 24, 2020 to Jan 27, 2020. The incidence of COVID-19 in the sample was 1.5‰ (95% CI: 0.31‰–4.37‰). Conclusion: Home quarantine has been effective in preventing the early transmission of COVID-19, but that more needs to be done to improve early detection of COVID-19 infection.


Pausing super spreader events for COVID-19 mitigation: International Hajj pilgrimage cancellation


title: Arenavirus Quasispecies and Their Biological Implications

text: The family Arenaviridae currently comprises over 20 viral species, each of them associated with a main rodent species as the natural reservoir and in one case possibly phyllostomid bats. Moreover, recent findings have documented a divergent group of arenaviruses in captive alethinophidian snakes. Human infections occur through mucosal exposure to aerosols or by direct contact of abraded skin with infectious materials. Arenaviruses merit interest both as highly tractable experimental model systems to study acute and persistent infections and as clinically important human pathogens including Lassa (LASV) and Junin (JUNV) viruses, the causative agents of Lassa and Argentine hemorrhagic fevers (AHFs), respectively, for which there are no FDA-licensed vaccines, and current therapy is limited to an off-label use of ribavirin (Rib) that has significant limitations. Arenaviruses are enveloped viruses with a bi-segmented negative strand (NS) RNA genome. Each genome segment, L (ca 7.3 kb) and S (ca 3.5 kb), uses an ambisense coding strategy to direct the synthesis of two polypeptides in opposite orientation, separated by a noncoding intergenic region (IGR). The S genomic RNA encodes the virus nucleoprotein (NP) and the precursor (GPC) of the virus surface glycoprotein that mediates virus receptor recognition and cell entry via endocytosis. The L genome RNA encodes the viral RNA-dependent RNA polymerase (RdRp, or L polymerase) and the small (ca 11 kDa) RING finger protein Z that has functions of a bona fide matrix protein including directing virus budding. Arenaviruses were thought to be relatively stable genetically with intra- and interspecies amino acid sequence identities of 90–95 % and 44–63 %, respectively. However, recent evidence has documented extensive arenavirus genetic variability in the field. Moreover, dramatic phenotypic differences have been documented among closely related LCMV isolates. These data provide strong evidence of viral quasispecies involvement in arenavirus adaptability and pathogenesis. Here, we will review several aspects of the molecular biology of arenaviruses, phylogeny and evolution, and quasispecies dynamics of arenavirus populations for a better understanding of arenavirus pathogenesis, as well as for the development of novel antiviral strategies to combat arenavirus infections.


The first Ramadan during COVID-19 pandemic: 1.8 billion Muslims should fast or not?


title: 5′- and 3′-noncoding regions in flavivirus RNA

text: Publisher Summary The flavivirus genome is a capped, positive-sense RNA approximately 10.5 kb in length. It contains a single long open reading frame (ORF), flanked by a 5´ noncoding regions (NCR), which is about 100 nucleotides in length, and a 3´ NCR ranging in size from about 400 to 800 nucleotides in length. The conserved structural and nucleotide sequence elements of these NCRs and their function in RNA replication and translation are the subjects of this chapter. The 5´ and 3´ NCRs play a role in the initiation of negative-strand synthesis on virus RNA released from entering virions, switching from negative-strand synthesis to synthesis of progeny plus strand RNA at late times after infection, and possibly in the initiation of translation and in the packaging of virus plus strand RNA into particles. The presence of conserved and nonconserved complementary nucleotide sequences near the 5´ and 3´ termini of flavivirus genomes suggests that ‘‘panhandle’’ or circular RNA structures are formed transiently by hydrogen bonding at some stage during RNA replication.


title: Modelling aerosol transport and virus exposure with numerical simulations in relation to SARS-CoV-2 transmission by inhalation indoors

text: Abstract We provide research findings on the physics of aerosol and droplet dispersion relevant to the hypothesized aerosol transmission of SARS-CoV-2 during the current pandemic. We utilize physics-based modeling at different levels of complexity, along with previous literature on coronaviruses, to investigate the possibility of airborne transmission. The previous literature, our 0D-3D simulations by various physics-based models, and theoretical calculations, indicate that the typical size range of speech and cough originated droplets ( d ⩽ 20 μ m ) allows lingering in the air for O ( 1 h ) so that they could be inhaled. Consistent with the previous literature, numerical evidence on the rapid drying process of even large droplets, up to sizes O ( 100 μ m ) , into droplet nuclei/aerosols is provided. Based on the literature and the public media sources, we provide evidence that the individuals, who have been tested positive on COVID-19, could have been exposed to aerosols/droplet nuclei by inhaling them in significant numbers e.g. O ( 100 ) . By 3D scale-resolving computational fluid dynamics (CFD) simulations, we give various examples on the transport and dilution of aerosols ( d ⩽ 20 μ m ) over distances O ( 10 m ) in generic environments. We study susceptible and infected individuals in generic public places by Monte-Carlo modelling. The developed model takes into account the locally varying aerosol concentration levels which the susceptible accumulate via inhalation. The introduced concept, ’exposure time’ to virus containing aerosols is proposed to complement the traditional ’safety distance’ thinking. We show that the exposure time to inhale O ( 100 ) aerosols could range from O ( 1 s ) to O ( 1 min ) or even to O ( 1 h ) depending on the situation. The Monte-Carlo simulations, along with the theory, provide clear quantitative insight to the exposure time in different public indoor environments.


Contrôle des épidémies de COVID-19 : la leçon de l'Islam


title: A Phased Approach to Resuming Suspended Allergy/Immunology Clinical Services

text: Abstract: In early 2020, the first US and Canadian cases of the novel SARS-CoV-2 infection were detected. In the ensuing months, there has been rapid spread of the infection. In March 2020, in response to the virus, state/provincial and local governments instituted shelter-in-place orders, and non-essential ambulatory care was significantly curtailed, including allergy/immunology services. With rates of new infections and fatalities potentially reaching a plateau and/or declining, restrictions on provision of routine ambulatory care are lifting, and there is a need to help guide the allergy/immunology clinician on how to re-initiate services. Given COVID-19 will circulate within our communities for months or longer, we present a flexible, algorithmic best-practices planning approach on how to prioritize services, in 4 stratified phases of re-opening according to community risk level, as well highlight key considerations for how to safely do so. The decisions on what services to offer and how fast to proceed are left to the discretion of the individual clinician and practice, operating in accordance with state and local ordinances with respect to the level of non-essential ambulatory care that can be provided. Clear communication with staff and patients before and after all changes should be incorporated into this new paradigm on continual change, given the movement may be forward and even backward through the phases as this is an evolving situation.


title: QT Interval Prolongation and Torsade De Pointes in Patients with COVID-19 treated with Hydroxychloroquine/Azithromycin

text: BACKGROUND: There is no known effective therapy for patients with COVID-19. Initial reports suggesting the potential benefit of Hydroxychloroquine/Azithromycin (HY/AZ) have resulted in massive adoption of this combination worldwide. However, while the true efficacy of this regimen is unknown, initial reports have raised concerns regarding the potential risk of QT prolongation and induction of torsade de pointes (TdP). OBJECTIVE: to assess the change in QTc interval and arrhythmic events in patients with COVID-19 treated with HY/AZ METHODS: This is a retrospective study of 251 patients from two centers, diagnosed with COVID-19 and treated with HY/AZ. We reviewed ECG tracings from baseline and until 3 days after completion of therapy to determine the progression of QTc and incidence of arrhythmia and mortality. RESULTS: QTc prolonged in parallel with increasing drug exposure and incompletely shortened after its completion. Extreme new QTc prolongation to > 500 ms, a known marker of high risk for TdP had developed in 23% of patients. One patient developed polymorphic ventricular tachycardia (VT) suspected as TdP, requiring emergent cardioversion. Seven patients required premature termination of therapy. The baseline QTc of patients exhibiting extreme QTc prolongation was normal. CONCLUSION: The combination of HY/AZ significantly prolongs the QTc in patients with COVID-19. This prolongation may be responsible for life threating arrhythmia in the form of TdP. This risk mandates careful consideration of HY/AZ therapy in lights of its unproven efficacy. Strict QTc monitoring should be performed if the regimen is given.


title: Attenuation of an original US porcine epidemic diarrhea virus strain PC22A via serial cell culture passage

text: Abstract Although porcine epidemic diarrhea (PED) has caused huge economic losses in the pork industry worldwide, an effective live, attenuated vaccine is lacking. In this study, an original US, highly virulent PED virus (PEDV) strain PC22A was serially passaged in Vero CCL81 and Vero BI cells. The virus growth kinetics in cell culture, virulence in neonatal pigs and the whole genomic sequences of selected passages were examined. Increased virus titers and sizes of syncytia were observed at the 65th passage level (P65) and P120, respectively. Based on the severity of clinical signs, histopathological lesions and the distribution of PEDV antigens in the gut, the virulence of P100 and above, but not P95C13 (CCL81), was markedly reduced in 4-day-old, caesarian-derived, colostrum-deprived piglets. Subsequently, the attenuation of P120 and P160 was confirmed in 4-day-old, conventional suckling piglets. Compared with P120, P160 replicated less efficiently in the intestine of pigs and induced a lower rate of protection after challenge. Sequence analysis revealed that the virulent viruses [P3 and P95C13 (CCL81)] had one, one, sixteen (including an early termination of nine amino acids) and two amino acid differences in non-structure protein 1 (nsp1), nsp4, spike and membrane proteins, respectively, from the fully attenuated P160. However, the overall pattern of attenuation-related genetic changes in PC22A differed from those of the other four pairs of PEDV wild type strains and their attenuated derivatives. These results suggest that PEDV attenuation can occur through multiple molecular mechanisms. The knowledge provides insights into potential molecular mechanisms of PEDV attenuation.


title: Chronic obstructive pulmonary disease in geriatric critical care

text: COPD is a progressive disorder that is punctuated in its later stages with acute exacerbations that present a risk for respiratory failure. COPD has a disproportionate impact on older patients. In the ICU, therapy is directed toward unloading fatigued respiratory muscles, treating airway infection, and prescribing bronchodilatory drugs. Most patients survive hospitalization in the ICU for an episode of respiratory failure. The severity of the underlying lung disease, however, underlies the poor outcomes of patients in terms of postdischarge survival and quality of life.


title: Emerging viral respiratory tract infections—environmental risk factors and transmission

text: Summary The past decade has seen the emergence of several novel viruses that cause respiratory tract infections in human beings, including Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia, an H7N9 influenza A virus in eastern China, a swine-like influenza H3N2 variant virus in the USA, and a human adenovirus 14p1 also in the USA. MERS-CoV and H7N9 viruses are still a major worldwide public health concern. The pathogenesis and mode of transmission of MERS-CoV and H7N9 influenza A virus are poorly understood, making it more difficult to implement intervention and preventive measures. A united and coordinated global response is needed to tackle emerging viruses that can cause fatal respiratory tract infections and to fill major gaps in the understanding of the epidemiology and transmission dynamics of these viruses.


title: Nucleotide sequence of coronavirus TGEV genomic RNA: evidence for 3 mRNA species between the peplomer and matrix protein genes

text: Abstract The region of the TGEV genome between the E1-matrix protein gene and the E2-peplomer protein gene has been sequenced from a cDNA clone. The consensus recognition sequence, 5 ′AA TT CTAAAC was found upstream from 3 large open reading frames. In coronaviruses these homologous recognition sequences are involved in the initiation of transcription suggesting that there are 3 mRNA species in this region of the TGEV genome. Northern blot analysis and nuclease S1 mapping confirmed the presence of 3 mRNA species between mRNA 3 encoding the E2-peplomer protein and mRNA 6 encoding the E1-matrix protein. The 5′ regions of these 3 mRNAs encode potential polypeptides of predicted molecular weight; 7859, 27744 and 9287, respectively. The potential translation product of ORF B (27744 Da) is considerably larger than previously reported and could be difficult to distinguish by size from the E1-matrix protein.


title: Interferon-inducible antiviral effectors

text: Since the discovery of interferons (IFNs), considerable progress has been made in describing the nature of the cytokines themselves, the signalling components that direct the cell response and their antiviral activities. Gene targeting studies have distinguished four effector pathways of the IFN-mediated antiviral response: the Mx GTPase pathway, the 2′-5′ oligoadenylate-synthetase-directed ribonuclease L pathway, the protein kinase R pathway and the ISG15 ubiquitin-like pathway. These effector pathways individually block viral transcription, degrade viral RNA, inhibit translation, and modify protein function to control all steps of viral replication. Ongoing research continues to expose additional activities for the effector proteins and has revealed unanticipated functions of the antiviral response.


title: Human Health Link to Invasive Species

text: Invasive species are currently a far-reaching, interdisciplinary topic given their broad impacts on biodiversity, economics, and human health, with representatives from all taxonomic levels (e.g., viruses, bacteria, algae, plants, invertebrates, large mammals). Researchers from different fields are working to build a framework for understanding how to best evaluate, quantify, and predict different kinds of impacts by non-indigenous species (NIS). In this context, there has been some controversy regarding the appropriate way to define invasive species and the invasion process, given the widespread use of these terms in both scientific and nonscientific frameworks. Although scientists have not unambiguously identified tax-independent characteristics that define all invasive species, the invasion process itself has been observed to progress through the same sequence of stages regardless of taxonomic identity (i.e. initial establishment, expansion, and saturation). Several non-exclusive hypotheses have been proposed to explain the successful establishment and spread of non-indigenous species in new environments. In the scenario of global change, species introductions and invasions are a major topic due to ecological impacts (e.g. changes in biodiversity), economic and social impacts (e.g. costs incurred for control or eradication or pests) and human health impacts (e.g. epidemics or increased exposure to hazards). Current research highlights the introduction and spread of non-indigenous species as both a consequence and cause of global change with repercussions on ecosystems, economies, and human societies.


title: Respiratory viruses in bronchiolitis and their link to recurrent wheezing and asthma

text: Bronchiolitis is the leading cause of hospitalization for children age <1 year and these hospitalized children have an increased risk of developing childhood asthma. It remains unclear, however, which children with severe bronchiolitis (e.g., an episode requiring hospitalization) will develop recurrent wheezing and/or asthma. Although many environmental and genetic factors may play a role in the pathway from bronchiolitis to asthma, this review focuses on the viruses that have been linked to bronchiolitis and how these viruses may predict or contribute to future wheezing and asthma. The review also discusses vitamin D as an emerging risk factor for respiratory infections and wheezing.


title: E-health in the East Asian tigers

text: Summary Objective: The article analyzes e-health progress in East Asia's leading tiger economies: Japan, Hong Kong, Singapore, South Korea and Taiwan. It describes five main dimensions of e-health provision in the tigers: policymaking, regulation, provision, funding and physician-patient relations. Methods: We conducted a series of fieldwork interviews and analyzed key healthcare websites. Results and Conclusion: Our main finding is that the development of e-health in the region is less advanced than might be expected. Our explanation focuses on institutional, cultural and financial factors.


title: Laboratory Surge Response to Pandemic (H1N1) 2009 Outbreak, New York City Metropolitan Area, USA

text: The North Shore–Long Island Jewish Health System Laboratories serve 15 hospitals and affiliated regional physician practices in the New York City metropolitan area, with virus testing performed at a central reference laboratory. The influenza A pandemic (H1N1) 2009 outbreak began in this area on April 24, 2009, and within weeks respiratory virus testing increased 7.5 times. In response, laboratory and client service workforces were increased, physical plant build-out was completed, testing paradigms were converted from routine screening tests and viral culture to a high-capacity molecular assay for respiratory viruses, laboratory information system interfaces were built, and same-day epidemiologic reports were produced. Daily review by leadership of data from emergency rooms, hospital facilities, and the Health System Laboratories enabled real-time management of unfolding events. The ability of System laboratories to rapidly increase to high-volume comprehensive diagnostics, including influenza A subtyping, provided key epidemiologic information for local and state public health departments.


title: A Centralized System to Access Acute Healthcare Services: The Pros and Cons

text: Abstract Having a centralized access service results in a daily interconnectedness between hospital sites, which can create many benefits but also much controversy. Knowing the pros and cons of a centralized service and understanding the role and work environment of the access coordinator will assist you in deciding if this service would be of benefit to your health region. In this descriptive analysis of a centralized access model, a regional perspective is presented; however many of the strategies can be adapted to a single hospital service resulting in improved flow in clinical areas.


MediPIET (2014-2017) a network for strengthening capacities for global health security through a regional field epidemiology training programme in the Mediterranean and Balck Sea regions


title: Covid-19 transmission, outcome and associated risk factors in cancer patients at the first month of the pandemic in a Spanish hospital in Madrid

text: BACKGROUND: There are no large reported series determining the Covid-19 cancer patient’s characteristics. We determine whether differences exist in cumulative incidence and mortality of Covid-19 infection between cancer patients and general population in Madrid. MATERIAL AND METHODS: We reviewed 1069 medical records of all cancer patients admitted at Oncology department between Feb 1 and April 7, 2020. We described Covid-19 cumulative incidence, treatment outcome, mortality, and associated risk factors. RESULTS: We detected 45/1069 Covid-19 diagnoses in cancer patients vs 42,450/6,662,000 in total population (p < 0.00001). Mortality rate: 19/45 cancer patients vs 5586/42,450 (p = 0.0001). Mortality was associated with older median age, adjusted by staging and histology (74 vs 63.5 years old, OR 1.06, p = 0.03). Patients who combined hydroxychloroquine and azithromycin presented 3/18 deaths, regardless of age, staging, histology, cancer treatment and comorbidities (OR 0.02, p = 0.03). CONCLUSION: Cancer patients are vulnerable to Covid-19 with an increase in complications. Combined hydroxychloroquine and azithromycin is presented as a good treatment option.


title: Gastrointestinal granuloma due to Candida albicans in an immunocompetent cat

text: A 3.5 year-old cat was admitted to the University of Melbourne Veterinary Teaching Hospital for chronic vomiting. Abdominal ultrasonography revealed a focal, circumferential thickening of the wall of the duodenum extending from the pylorus aborally for 3 cm, and an enlarged gastric lymph node. Cytology of fine-needle aspirates of the intestinal mass and lymph node revealed an eosinophilic inflammatory infiltrate and numerous extracellular septate acute angle branching fungal-type hyphae. Occasional hyphae had globose terminal ends, as well as round to oval blastospores and germ tubes. Candida albicans was cultured from a surgical biopsy of the duodenal mass. No underlying host immunodeficiencies were identified. Passage of an abrasive intestinal foreign body was suspected to have caused intestinal mucosal damage resulting in focal intestinal candidiasis. The cat was treated with a short course of oral itraconazole and all clinical signs resolved.


Please cite this paper as: Vongphrachanh P, Simmerman JM, Phonekeo D, Pansayavong V, Sisouk T, Ongkhamme S, Bryce GT, Corwin A, Bryant JE. An early report from newly established laboratory‐based influenza surveillance in Lao PDR. Influenza and Other Respiratory Viruses 4(2), 47–52. Background Prior to 2007, little information was available about the burden of influenza in Laos. We report data from the first laboratory‐based influenza surveillance system established in the Lao People’s Democratic Republic. Methods Three hospitals in the capital city of Vientiane began surveillance for influenza‐like illness (ILI) in outpatients in 2007 and expanded to include hospitalized pneumonia patients in 2008. Nasal/throat swab specimens were collected and tested for influenza and other respiratory viruses by multiplex ID‐Tag(TM) respiratory viral panel (RVP) assay on a Luminex® 100× MAP IS instrument (Qiagen, Singapore). Results During January 2007 to December 2008, 287 of 526 (54·6%) outpatients with ILI were positive for at least one respiratory virus. Influenza was most commonly identified, with 63 (12·0%) influenza A and 92 (17·5%) influenza B positive patients identified. In 2008, six of 79 (7·6%) hospitalized pneumonia patients were positive for influenza A and four (5·1%) were positive for influenza B. Children <5 years represented 19% of viral infections in outpatients and 38% of pneumonia inpatients. Conclusion Our results provide the first documentation of influenza burden among patients with febrile respiratory illness and pneumonia requiring hospitalization in Laos. Implementing laboratory‐based influenza surveillance requires substantial investments in infrastructure and training. However, continuing outbreaks of avian influenza A/H5N1 in poultry and emergence of the 2009 influenza A(H1N1) pandemic strain further underscore the importance of establishing and maintaining influenza surveillance in developing countries.


title: Dissection of Influenza Infection In Vivo by Single-Cell RNA Sequencing

text: Summary The influenza virus is a major cause of morbidity and mortality worldwide. Yet, both the impact of intracellular viral replication and the variation in host response across different cell types remain uncharacterized. Here we used single-cell RNA sequencing to investigate the heterogeneity in the response of lung tissue cells to in vivo influenza infection. Analysis of viral and host transcriptomes in the same single cell enabled us to resolve the cellular heterogeneity of bystander (exposed but uninfected) as compared with infected cells. We reveal that all major immune and non-immune cell types manifest substantial fractions of infected cells, albeit at low viral transcriptome loads relative to epithelial cells. We show that all cell types respond primarily with a robust generic transcriptional response, and we demonstrate novel markers specific for influenza-infected as opposed to bystander cells. These findings open new avenues for targeted therapy aimed exclusively at infected cells.


title: A Serological Survey of Selected Pathogens in Wild Boar in Slovenia

text: Serum samples collected from 178 shot wild boars (Sus scrofa) were tested for the presence of antibodies against classical swine fever virus, Aujeszky's disease virus (ADV), porcine reproductive and respiratory syndrome virus, porcine respiratory coronavirus (PRCV), transmissible gastroenteritis virus, swine influenza virus, porcine parvovirus (PPV), swine vesicular disease virus, Actinobacillus pleuropneumoniae (APP), Mycoplasma hyopneumoniae, Salmonella spp., Brucella spp. and Haemophilus parasuis (HPS) throughout Slovenia during the hunting season 2003/2004. The number of samples corresponds to 3% of the total hunting bag. By enzyme‐linked immunosorbent assay (ELISA) antibodies against ADV were detected in 55 sera (31%), against PRCV in five sera (3%), PPV in 87 sera (49%), APP in 93 sera (52%), M. hyopneumoniae in 38 sera (21%), Salmonella spp. in 85 sera (47%) and HPS in 33 sera (18%).


title: Chapter 25 Respiratory tract viruses

text: Summary Respiratory tract infections are among the commonest of illnesses, and most individuals will experience two to five infections during each year of their lives. The illnesses vary from relatively mild common colds caused by rhinoviruses and coronaviruses, to severe bronchiolitis and pneumonia caused by adenoviruses and influenza viruses and respiratory syncytial virus (RSV) in infants: the former is associated with little morbidity and no mortality, while influenza is responsible annually for between 1 and 25 thousand deaths per 50 million population. Over 140 viruses cause respiratory tract infections, with the added complications of influenza viruses where new antigenic variants are recognized almost annually; and immunity to infection by one virus strain offers little or no protection to infection by others. Knowledge of the mechanisms of spread of respiratory viruses is largely understood and has helped in infection control; however, the clinical signs and symptoms of infection tend not to be diagnostic of the causative agent; and although vaccines have been developed for the more serious infections such as influenza and some adenovirus infection, none are available for other important infections. Treatment is largely symptomatic, but the compounds ribovirin for RSV infection and amantadine for influenza virus infection have been shown to be effective. Much remains to be discovered before more effective measures can be implemented to limit the enormous costs incurred by these infections. The number of viruses involved is large, and the spectrum of illness complex: in the present chapter, the viruses are described, together with the features of the epidemiology, pathogenesis, clinical disease, and treatment.


title: The p7 protein of the hepatitis C virus induces cell death differently from the influenza A virus viroporin M2

text: Abstract Most viruses encode proteins that modulate cell-death signaling by the host. For hepatitis C virus (HCV) infection, apoptosis and other forms of cell-death have been observed in vitro and in vivo but the detailed understanding of this intricate viral-host interplay is unclear. This study examined the role played by the HCV p7 protein in the induction of cell-death. By measuring caspase-3/7 activation and cleavage of endogenous PARP, two hallmarks of apoptosis, the overexpression of p7 protein was shown to induce apoptosis in Huh7.5 cells. Furthermore, p7-induced apoptosis is caspase-dependent and involves both the intrinsic and extrinsic pathways. Similar to the M2 protein of influenza A virus, p7-induced apoptosis is independent of its ion channel activity. Coimmunoprecipitation experiments further showed that both M2 and p7 interact with the essential autophagy protein Beclin-1. However, only the M2 protein could cause an increase in the level of LC3-II, which is an indicator of autophagic activity. Thus, although the p7 protein is functionally similar to the well-characterized M2 protein, they differ in their activation of autophagic cell-death. Taken together, these results shed more light on the relationship between the HCV p7 ion channel protein and cell-death induction in host cells.


title: Early transmission of SARS-CoV-2 in South Africa: An epidemiological and phylogenetic report

text: BACKGROUND: The emergence of a novel coronavirus, SARS-CoV-2, in December 2019, progressed to become a world pandemic in a few months and reached South Africa at the beginning of March. To investigate introduction and understand the early transmission dynamics of the virus, we formed the South African Network for Genomics Surveillance of COVID (SANGS_COVID), a network of ten government and university laboratories. Here, we present the first results of this effort, which is a molecular epidemiological study of the first twenty-one SARS-CoV-2 whole genomes sampled in the first port of entry, KwaZulu-Natal (KZN), during the first month of the epidemic. By combining this with calculations of the effective reproduction number (R), we aim to shed light on the patterns of infections that define the epidemic in South Africa. METHODS: R was calculated using positive cases and deaths from reports provided by the four major provinces. Molecular epidemiology investigation involved sequencing viral genomes from patients in KZN using ARCTIC protocols and assembling whole genomes using meticulous alignment methods. Phylogenetic analysis was performed using maximum likelihood (ML) and Bayesian trees, lineage classification and molecular clock calculations. FINDINGS: The epidemic in South Africa has been very heterogeneous. Two of the largest provinces, Gauteng, home of the two large metropolis Johannesburg and Pretoria, and KwaZulu-Natal, home of the third largest city in the country Durban, had a slow growth rate on the number of detected cases. Whereas, Western Cape, home of Cape Town, and the Eastern Cape provinces the epidemic is spreading fast. Our estimates of transmission potential for South Africa suggest a decreasing transmission potential towards R=1 since the first cases and deaths have been reported. However, between 06 May and 18 May 2020, we estimate that R was on average 1.39 (1.04 – 2.15, 95% CI). We also demonstrate that early transmission in KZN, and most probably in all main regions of SA, was associated with multiple international introductions and dominated by lineages B1 and B. The study also provides evidence for locally acquired infections in a hospital in Durban within the first month of the epidemic, which inflated early mortality in KZN. INTERPRETATION: This first report of SANGS_COVID consortium focuses on understanding the epidemic heterogeneity and introduction of SARS-CoV-2 strains in the first month of the epidemic in South Africa. The early introduction of SARS-CoV-2 in KZN included caused a localized outbreak in a hospital, provides potential explanations for the initially high death rates in the province. The current high rate of transmission of COVID-19 in the Western Cape and Eastern Cape highlights the crucial need to strength local genomic surveillance in South Africa. FUNDING: UKZN Flagship Program entitled: Afrocentric Precision Approach to Control Health Epidemic, by a research Flagship grant from the South African Medical Research Council (MRC-RFA-UFSP-01-2013/UKZN HIVEPI, by the the Technology Innovation Agency and the the Department of Science and Innovation and by National Human Genome Re- search Institute of the National Institutes of Health under Award Number U24HG006941. H3ABioNet is an initiative of the Human Health and Heredity in Africa Consortium (H3Africa).


title: Differential Cell Count and CRP Level in Blood as Predictors for Middle East Respiratory Syndrome Coronavirus Infection in Acute Febrile Patients during Nosocomial Outbreak

text: A case-control study was performed to identify clinical predictors for Middle East respiratory syndrome coronavirus (MERS-CoV) infection among patients with acute febrile illness during the nosocomial outbreak. Patients with MERS-CoV were more likely to have monocytosis with normal white blood cell (WBC) count and lower C-reactive protein (CRP) level. Simple laboratory data such as complete blood counts (CBC) with differential count could be a useful marker for the prediction of MERS and triage at the initial presentation of acute febrile patients in outbreak setting.


title: Factors associated with system-level activities for patient safety and infection control

text: Abstract Objective We examined the relationship between hospital structural characteristics and system-level activities for patient safety and infection control, for use in designing an incentive structure to promote patient safety. Methods This study utilized a questionnaire to collect institutional data about hospital infrastructure and volume of patient safety activities from all 1039 teaching hospitals in Japan. The patient safety activities were focused on meetings and conferences, internal audits, staff education and training, incident reporting and infection surveillance. Generalized linear modeling was used. Results Of the 1039 hospitals surveyed, 418 (40.2%) hospitals participated. The amount of activities significantly increased by over 30% in hospitals with dedicated patient safety and infection control full-time staff (P <0.001 and P <0.01, respectively). High profit margins also predicted the increase of patient safety programs (P <0.01). Perceived lack of administrative leadership was associated with reduced volume of activities (P <0.05), and the economic burden of safety programs was found to be disproportionately large for small hospitals (P <0.05). Conclusions Hospitals with increased resources had greater spread of patient safety and infection control activities. To promote patient safety programs in hospitals, it is imperative that policy makers require the assignment of dedicated full-time staff to patient safety. Economic support for hospitals will also be required to assure that safety programs are sustainable.


title: Allelic Variation in CXCL16 Determines CD3(+) T Lymphocyte Susceptibility to Equine Arteritis Virus Infection and Establishment of Long-Term Carrier State in the Stallion

text: Equine arteritis virus (EAV) is the causative agent of equine viral arteritis (EVA), a respiratory, systemic, and reproductive disease of horses and other equid species. Following natural infection, 10–70% of the infected stallions can become persistently infected and continue to shed EAV in their semen for periods ranging from several months to life. Recently, we reported that some stallions possess a subpopulation(s) of CD3(+) T lymphocytes that are susceptible to in vitro EAV infection and that this phenotypic trait is associated with long-term carrier status following exposure to the virus. In contrast, stallions not possessing the CD3(+) T lymphocyte susceptible phenotype are at less risk of becoming long-term virus carriers. A genome wide association study (GWAS) using the Illumina Equine SNP50 chip revealed that the ability of EAV to infect CD3(+) T lymphocytes and establish long-term carrier status in stallions correlated with a region within equine chromosome 11. Here we identified the gene and mutations responsible for these phenotypes. Specifically, the work implicated three allelic variants of the equine orthologue of CXCL16 (EqCXCL16) that differ by four non-synonymous nucleotide substitutions (XM_00154756; c.715 A → T, c.801 G → C, c.804 T → A/G, c.810 G → A) within exon 1. This resulted in four amino acid changes with EqCXCL16S (XP_001504806.1) having Phe, His, Ile and Lys as compared to EqCXL16R having Tyr, Asp, Phe, and Glu at 40, 49, 50, and 52, respectively. Two alleles (EqCXCL16Sa, EqCXCL16Sb) encoded identical protein products that correlated strongly with long-term EAV persistence in stallions (P<0.000001) and are required for in vitro CD3(+) T lymphocyte susceptibility to EAV infection. The third (EqCXCL16R) was associated with in vitro CD3(+) T lymphocyte resistance to EAV infection and a significantly lower probability for establishment of the long-term carrier state (viral persistence) in the male reproductive tract. EqCXCL16Sa and EqCXCL16Sb exert a dominant mode of inheritance. Most importantly, the protein isoform EqCXCL16S but not EqCXCL16R can function as an EAV cellular receptor. Although both molecules have equal chemoattractant potential, EqCXCL16S has significantly higher scavenger receptor and adhesion properties compared to EqCXCL16R.


Metabolic disorders in foals


title: Downregulation of angiotensin-converting enzyme 2 by the neuraminidase protein of influenza A (H1N1) virus

text: Abstract Influenza A (H1N1) virus, a high-risk infectious pathogen, can cause severe acute lung injury leading to significant morbidity and mortality. Angiotensin-converting enzyme 2 (ACE2), a negative regulator of the renin-angiotensin system (RAS), plays a protective role in pathogenesis of acute lung injury. Here, we showed that ACE2 protein levels were significantly downregulated after infection with H1N1 viruses but was dispensable for viral replication. ACE2 protein downregulation was most likely related to ACE2 protein degradation by proteasome pathway rather than ACE2 shedding. Finally, we found that ACE2 cleavage could be regulated by influenza neuraminidase (NA), which was fundamentally different from the classically sheddase-induced proteolytic cleavage of ACE2.


title: Procalcitonin Accurately Identifies Hospitalized Children With Low Risk of Bacterial Community-Acquired Pneumonia

text: BACKGROUND: Lower procalcitonin (PCT) concentrations are associated with reduced risk of bacterial community-acquired pneumonia (CAP) in adults, but data in children are limited. METHODS: We analyzed serum PCT concentrations from children hospitalized with radiographically confirmed CAP enrolled in the Centers for Disease Control and Prevention’s Etiology of Pneumonia in the Community (EPIC) Study. Blood and respiratory specimens were tested using multiple pathogen detection methods for typical bacteria (eg, Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus), atypical bacteria (Mycoplasma pneumoniae and Chlamydophila pneumoniae), and respiratory viruses. Multivariable regression was used to assess associations between PCT concentrations and etiology and severity. RESULTS: Among 532 children (median age, 2.4 years; interquartile range [IQR], 1.0–6.3), patients with typical bacteria had higher PCT concentrations (±viruses; n = 54; median, 6.10; IQR, 0.84–22.79 ng/mL) than those with atypical bacteria (±viruses; n = 82; median, 0.10; IQR, 0.06–0.39 ng/mL), viral pathogens only (n = 349; median, 0.33; IQR, 0.12–1.35 ng/mL), or no pathogen detected (n = 47; median, 0.44; IQR, 0.10–1.83 ng/mL) (P < .001 for all). No child with PCT <0.1 ng/mL had typical bacteria detected. Procalcitonin <0.25 ng/mL featured a 96% negative predictive value (95% confidence interval [CI], 93–99), 85% sensitivity (95% CI, 76–95), and 45% specificity (95% CI, 40–50) in identifying children without typical bacterial CAP. CONCLUSIONS: Lower PCT concentrations in children hospitalized with CAP were associated with a reduced risk of typical bacterial detection and may help identify children who would not benefit from antibiotic treatment.


A new pathogenic human parvovirus


Cloning of a Gene Involved in Antibiotic Synthesis


title: A quickly, effectively screening process of novel corona virus disease 2019 (COVID-19) in children in Shanghai, China

text: Background: A recent cluster of pneumonia cases in China was caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report the screening and diagnosis of corona virus disease 2019 (COVID-19) in our hospital. Methods: Developed a procedure for the identification of children cases with COVID-19 in outpatient and emergency department of our hospital, then we observed how this process works. Results: (I) There were 56 cases considered suspected cases, and 10 cases were confirmed as COVID-19. (II) Of the 10 confirmed COVID-19 cases admitted in our hospital, 5 were males and 5 were females, aged from 7 months to 11 years, the average age is 6.0±4.2 years, 6 cases were mild pneumonia, the others were upper respiratory tract infection. (III) We followed up 68 patients in isolation at home until symptoms disappeared. Non were missed in the patient's first visit. The sensitivity of this method is 100% and the specificity is 71.3%. Conclusions: Our screening process works well, and it is also necessary to establish a screening network in the hospital.


title: Impact of Covid-19 lockdown on PM(10), SO(2) and NO(2) concentrations in Salé City (Morocco)

text: Covid-19 was first reported in Morocco on March 2, 2020. Since then, to prevent its propagation, the Moroccan government declared a state of health emergency. A set of rapid and strict countermeasures have taken, including locking down cities, limiting population's mobility and prohibiting almost all avoidable activities. In the present study, we attempted to evaluate the changes in levels of some air pollutants (mainly PM(10), NO(2) and SO(2)) in Salé city (North-Western Morocco) during the lockdown measures. In this context, a continuous measurement of PM(10), SO(2) and NO(2) was carried before and during the Covid-19 lockdown period. As a consequence of the security measures and control actions undertaken, the emissions from vehicle exhaust and industrial production were significantly reduced, which contribute to the decrease in the concentrations of the studied pollutants. The obtained results showed that the difference between the concentrations recorded before and during the lockdown period were respectively 75%, 49% and 96% for PM(10), SO(2) and NO(2). PM(10) levels were much less reduced than NO(2). The three-dimensional air mass backward trajectories, using the HYSPLIT model, demonstrated the benefits of PM(10) local emission reductions related to the lockdown were overwhelmed by the contribution of long-range transported aerosols outside areas. In addition, noteworthy differences in the air mass back trajectories and the meteorology between these two periods were evidenced.


The surgeon and the COVID-19 pandemic - Perspective


title: A Novel Gene Underlies Bleomycin-Response Variation in Caenorhabditis elegans

text: Bleomycin is a powerful chemotherapeutic drug used to treat a variety of cancers. However, individual patients vary in their responses to bleomycin. The identification of genetic differences that underlie this response variation could improve treatment outcomes by tailoring bleomycin dosages to each patient. We used the model organism Caenorhabditis elegans to identify genetic determinants of bleomycin-response differences by performing linkage mapping on recombinants derived from a cross between the laboratory strain (N2) and a wild strain (CB4856). This approach identified a small genomic region on chromosome V that underlies bleomycin-response variation. Using near-isogenic lines, and strains with CRISPR-Cas9 mediated deletions and allele replacements, we discovered that a novel nematode-specific gene (scb-1) is required for bleomycin resistance. Although the mechanism by which this gene causes variation in bleomycin responses is unknown, we suggest that a rare variant present in the CB4856 strain might cause differences in the potential stress-response function of scb-1 between the N2 and CB4856 strains, thereby leading to differences in bleomycin resistance.


title: Perspective: Vitamin D deficiency and COVID‐19 severity – plausibly linked by latitude, ethnicity, impacts on cytokines, ACE2, and thrombosis (R1)

text: BACKGROUND: SARS‐CoV‐2 coronavirus infection ranges from asymptomatic through to fatal COVID‐19 characterised by a “cytokine storm” and lung failure. Vitamin D deficiency has been postulated as a determinant of severity. OBJECTIVES: To review the evidence relevant to vitamin D and COVID‐19 METHODS: Narrative review RESULTS: Regression modelling shows that more northerly countries in the Northern Hemisphere are currently (May 2020) showing relatively high COVID‐19 mortality, with an estimated 4.4% increase in mortality for each 1 degree latitude north of 28 degrees North (P=0.031) after adjustment for age of population. This supports a role for ultraviolet B acting via vitamin D synthesis. Factors associated with worse COVID‐19 prognosis include old age, ethnicity, male sex, obesity, diabetes and hypertension and these also associate with deficiency of vitamin D or its response. Vitamin D deficiency is also linked to severity of childhood respiratory illness. Experimentally, vitamin D increases the ratio of angiotensin converting enzyme 2 (ACE2) to ACE, thus increasing angiotensin II hydrolysis and reducing subsequent inflammatory cytokine response to pathogens and lung injury. CONCLUSIONS: Substantial evidence supports a link between vitamin D deficiency and COVID‐19 severity but it is all indirect. Community‐based placebo‐controlled trials of vitamin D supplementation may be difficult. Further evidence could come from study of COVID‐19 outcomes in large cohorts with information on prescribing data for vitamin D supplementation or assay of serum unbound 25(OH) vitamin D levels. Meanwhile vitamin D supplementation should be strongly advised for people likely to be deficient.


title: Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study

text: BACKGROUND: Since June, 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) has, worldwide, caused 104 infections in people including 49 deaths, with 82 cases and 41 deaths reported from Saudi Arabia. In addition to confirming diagnosis, we generated the MERS-CoV genomic sequences obtained directly from patient samples to provide important information on MERS-CoV transmission, evolution, and origin. METHODS: Full genome deep sequencing was done on nucleic acid extracted directly from PCR-confirmed clinical samples. Viral genomes were obtained from 21 MERS cases of which 13 had 100%, four 85–95%, and four 30–50% genome coverage. Phylogenetic analysis of the 21 sequences, combined with nine published MERS-CoV genomes, was done. FINDINGS: Three distinct MERS-CoV genotypes were identified in Riyadh. Phylogeographic analyses suggest the MERS-CoV zoonotic reservoir is geographically disperse. Selection analysis of the MERS-CoV genomes reveals the expected accumulation of genetic diversity including changes in the S protein. The genetic diversity in the Al-Hasa cluster suggests that the hospital outbreak might have had more than one virus introduction. INTERPRETATION: We present the largest number of MERS-CoV genomes (21) described so far. MERS-CoV full genome sequences provide greater detail in tracking transmission. Multiple introductions of MERS-CoV are identified and suggest lower R(0) values. Transmission within Saudi Arabia is consistent with either movement of an animal reservoir, animal products, or movement of infected people. Further definition of the exposures responsible for the sporadic introductions of MERS-CoV into human populations is urgently needed. FUNDING: Saudi Arabian Ministry of Health, Wellcome Trust, European Community, and National Institute of Health Research University College London Hospitals Biomedical Research Centre.


title: Aetiological role of common respiratory viruses in acute lower respiratory infections in children under five years: A systematic review and meta–analysis

text: BACKGROUND: Acute lower respiratory infection (ALRI) remains a major cause of childhood hospitalization and mortality in young children and the causal attribution of respiratory viruses in the aetiology of ALRI is unclear. We aimed to quantify the absolute effects of these viral exposures. METHODS: We conducted a systematic literature review (across 7 databases) of case–control studies published from 1990 to 2014 which investigated the viral profile of 18592 children under 5 years with and without ALRI. We then computed a pooled odds ratio and virus–specific attributable fraction among the exposed of 8 common viruses – respiratory syncytial virus (RSV), influenza (IFV), parainfluenza (PIV), human metapneumovirus (MPV), adenovirus (AdV), rhinovirus (RV), bocavirus (BoV), and coronavirus (CoV). FINDINGS: From the 23 studies included, there was strong evidence for causal attribution of RSV (OR 9.79; AFE 90%), IFV (OR 5.10; AFE 80%), PIV (OR 3.37; AFE 70%) and MPV (OR 3.76; AFE 73%), and less strong evidence for RV (OR 1.43; AFE 30%) in young children presenting with ALRI compared to those without respiratory symptoms (asymptomatic) or healthy children. However, there was no significant difference in the detection of AdV, BoV, or CoV in cases and controls. CONCLUSIONS: This review supports RSV, IFV, PIV, MPV and RV as important causes of ALRI in young children, and provides quantitative estimates of the absolute proportion of virus–associated ALRI cases to which a viral cause can be attributed.


title: The costs of preventing the spread of respiratory infection in family physician offices: a threshold analysis

text: BACKGROUND: Influenza poses concerns about epidemic respiratory infection. Interventions designed to prevent the spread of respiratory infection within family physician (FP) offices could potentially have a significant positive influence on the health of Canadians. The main purpose of this paper is to estimate the explicit costs of such an intervention. METHODS: A cost analysis of a respiratory infection control was conducted. The costs were estimated from the perspective of provincial government. In addition, a threshold analysis was conducted to estimate a threshold value of the intervention's effectiveness that could generate potential savings in terms of averted health-care costs by the intervention that exceed the explicit costs. The informational requirements for these implicit costs savings are high, however. Some of these elements, such as the cost of hospitalization in the event of contacting influenza, and the number of patients passing through the physicians' office, were readily available. Other pertinent points of information, such as the proportion of infected people who require hospitalization, could be imported from the existing literature. We take an indirect approach to calculate a threshold value for the most uncertain piece of information, namely the reduction in the probability of the infection spreading as a direct result of the intervention, at which the intervention becomes worthwhile. RESULTS: The 5-week intervention costs amounted to a total of $52,810.71, or $131,094.73 prorated according to the length of the flu season, or $512,729.30 prorated for the entire calendar year. The variable costs that were incurred for this 5-week project amounted to approximately $923.16 per participating medical practice. The (fixed) training costs per practice were equivalent to $73.27 for the 5-week intervention, or $28.14 for 13-week flu season, or $7.05 for an entire one-year period. CONCLUSION: Based on our conservative estimates for the direct cost savings, there are indications that the outreach facilitation intervention program would be cost effective if it can achieve a reduction in the probability of infection on the order of 0.83 (0.77, 1.05) percentage points. A facilitation intervention initiative tailored to the environment and needs of the family medical practice and walk-in clinics is of promise for improving respiratory infection control in the physicians' offices.


title: Infection control measures of a Taiwanese hospital to confront the COVID‐19 pandemic

text: The World Health Organization announced the coronavirus disease 2019 (COVID‐19) outbreak a pandemic on 12 March 2020. Although being in proximity to China, the original epicenter of the COVID‐19 outbreak, Taiwan has maintained a low number of COVID‐19 cases despite its close social ties and heavy traffic between Taiwan and China. Containment strategies executed by the Taiwanese government have attracted global attention. Similarly, in‐hospital settings, high alertness and swift responses to the changing outbreak situation are necessary to ensure hospital staff members' safety so they can continue to save patients' lives. Herein, we present infection control measures that can be adopted in hospital settings that were executed in a Taiwanese hospital to confront the COVID‐19 pandemic, including emergency preparedness and responses from the hospital administration, education, surveillance, patient flow arrangement, the partition of hospital zones, and the prevention of a systemic shutdown by using the “divided cabin, divided flow” strategy. The measures implemented by a Taiwan hospital during the COVID‐19 pandemic may not be universally applicable in every hospital. Nonetheless, the presented infection control methods have been practically executed and can be referenced or modified to fit each hospital's unique condition.


title: SARS-CoV-2 Infection of Pluripotent Stem Cell-derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response

text: The most severe and fatal infections with SARS-CoV-2 result in the acute respiratory distress syndrome, a clinical phenotype of coronavirus disease 2019 (COVID-19) that is associated with virions targeting the epithelium of the distal lung, particularly the facultative progenitors of this tissue, alveolar epithelial type 2 cells (AT2s). Little is known about the initial responses of human lung alveoli to SARS-CoV-2 infection due in part to inability to access these cells from patients, particularly at early stages of disease. Here we present an in vitro human model that simulates the initial apical infection of the distal lung epithelium with SARS-CoV-2, using AT2s that have been adapted to air-liquid interface culture after their derivation from induced pluripotent stem cells (iAT2s). We find that SARS-CoV-2 induces a rapid global transcriptomic change in infected iAT2s characterized by a shift to an inflammatory phenotype predominated by the secretion of cytokines encoded by NF-kB target genes, delayed epithelial interferon responses, and rapid loss of the mature lung alveolar epithelial program. Over time, infected iAT2s exhibit cellular toxicity that can result in the death of these key alveolar facultative progenitors, as is observed in vivo in COVID-19 lung autopsies. Importantly, drug testing using iAT2s confirmed the efficacy of TMPRSS2 protease inhibition, validating putative mechanisms used for viral entry in human alveolar cells. Our model system reveals the cell-intrinsic responses of a key lung target cell to infection, providing a platform for further drug development and facilitating a deeper understanding of COVID-19 pathogenesis.


title: Reflections on scrapie and related disorders, with consideration of the possibility of a viral aetiology

text: The transmissible spongiform encephalopathies of domesticated animals, scrapie in-sheep and bovine spongiform encephalopathy (BSE), and transmissible mink encephalopathy are more than a scientific curiosity; under certain circumstances their impact on commercial activities can be calamitous. Knowledge of their causation and pathogenesis is still rudimentary, but many consider than an unconventional agent, the prion (a brain protein, PrP), that is not associated with nucleic acid is involved in both. Others believe that conventional viruses, which replicate by virtue of their nucleic acid-defined genes, are involved in the causation and progression of the encephalopathies but that technical problems have prevented their identification. Others postulate even more exotic causative agents. While this paper will particularly address the possibility of a viral aetiology for these diseases, it is also emphasized that our knowledge of the state of the immune system in animals with encephalopathy needs broadening. There are remarkable gaps in our knowledge of the histopathology of these diseases, particularly the nature of the characteristic vacuoles. Much further work is needed on the biochemical changes in the brain and the serum, particularly of the latter as it could lead to an additional means of recognizing clinical cases without waiting for the animal to die with subsequent examination of the brain for characteristic lesions and the presence of protease-K-resistant PrP.


title: A novel multiplex PCR-electronic microarray assay for rapid and simultaneous detection of bovine respiratory and enteric pathogens

text: Abstract Respiratory and enteric diseases continue to be two major causes of economic losses to the cattle industry worldwide. Despite their multifactorial etiology, the currently available diagnostic tests for bovine respiratory disease complex (BRDC) and bovine enteric disease (BED) are single-pathogen-tests. DNA microarray when combined with multiplex polymerase chain reaction (PCR) is a powerful tool in detection and differentiation of multiple pathogens in a single sample. This study reports development and initial validation of two independent highly sensitive and specific multiplex PCR-electronic microarray assays, one for the detection and differentiation of pathogens of the BRDC and the other for detection and differentiation of pathogens of the BED. The BRDC multiplex PCR-microarray assay was able to detect and differentiate four bacteria (Mannheimia haemolytica, Histophilus somni, Pasteurella multocida, and Mycoplasma bovis) and five viruses [bovine parainfluenza virus-3, bovine respiratory syncytial virus, bovine herpesvirus-1, bovine coronavirus (BCoV), and bovine viral diarrhea virus (BVDV)] associated with BRDC. The BED multiplex PCR- microarray- assay was able to detect and differentiate four bacteria (Clostridium perfringens, Escherichia coli, Salmonella enterica Dublin, and Salmonella enterica Typhimurium), three protozoa (Eimeria zuernii, Eimeria bovis, and Cryptosporidium parvum), and four viruses (bovine torovirus, bovine rotavirus, BCoV, and BVDV) associated with the BED. Both assays detected their respective targets individually or in combination when present. The limit-of-detection of each assay at the PCR amplification and DNA microarray levels was determined using previously titrated laboratory amplified target pathogens or using quantified synthetic nucleotides. Both assays showed very high analytical sensitivity and specificity, and were validated using a limited number of clinical samples. The BRDC and BED multiplex PCR- microarray-assays developed in this study, with further clinical validation, could be used in veterinary diagnostic laboratories for the rapid and simultaneous identification of pathogens to facilitate quick and accurate decision making for the control and treatment of these two economically important disease complexes. Furthermore, these assays could be very effective tools in epidemiological studies as well as for screening of healthy animals to identify carriers that may potentially develop BRDC or BED.


Response to recent commentaries regarding the involvement of angiotensin‐converting enzyme 2 (ACE2) and renin‐angiotensin system blockers in SARS‐CoV‐2 infections


GUÍA BÁSICA Ecografía Pulmonar y COVID-19


title: Public health and medical care for the world's factory: China's Pearl River Delta Region

text: While the growth of urbanization, worldwide, has improved the lives of migrants from the hinterland, it also raises health risks related to population density, concentrated poverty and the transmission of infectious disease. Will megacity regions evolve into socially infected breeding grounds for the rapid transmission of disease, or can they become critical spatial entities for the protection and promotion of population health? We address this question for the Pearl River Delta Region (PRD) based on recent data from Chinese sources, and on the experience of how New York, Greater London, Tokyo and Paris have grappled with the challenges of protecting population health and providing their populations with access to health care services. In some respects, there are some important lessons from comparative experience for PRD, notably the importance of covering the entire population for health care services and targeting special programs for those at highest risk for disease. In other respects, PRD's growth rate and sheer scale make it a unique megacity region that already faces new challenges and will require new solutions.


Introduction to the special issue on COVID‐19 and the Canadian agriculture and food sectors: Thoughts from the pandemic onset


title: Caring for bereaved family members during the COVID-19 pandemic: before and after the death of a patient

text: Abstract Bereavement care is considered an integral component of quality end-of-life care endorsed by the palliative care movement. However, few hospitals and health care institutions offer universal bereavement care to all families of patients who die. The current COVID-19 pandemic has highlighted this gap and created a sense of urgency, from a public health perspective, for institutions to provide support to bereaved family members. In this article, drawing upon the palliative care and bereavement literature, we offer suggestions about how to incorporate palliative care tools and psychological strategies into bereavement care for families during this pandemic.


title: In Preparation for Outdoor Pharming: Griffithsin Can Be Expressed in Nicotiana excelsiana and Retains Activity After Storage as Silage

text: Griffithsin is an algae-derived lectin with strong anti-viral activity against HIV and a positive safety profile. Multiple clinical studies are investigating griffithsin's utility as topical HIV microbicide. HIV microbicides are an extremely cost-sensitive market and plant-based griffithsin protein expression has the potential to meet those demands. The griffithsin product used in the clinic has been expressed and purified in N. benthamiana, using a TMV-based viral vector system, Geneware®. Outdoor pharming of biopharmaceuticals would further alleviate startup costs for biotechnology firms and may allow broader product accessibility. Therefore, this study assessed expression in a hybrid tobacco line, N. excelsiana, that is susceptible to TMV-based viral vectors and can be grown outdoors. In addition to using this hybrid line we expand on methods for in planta storage of griffithsin in leafy plants by ensiling kilogram quantities of griffithsin. The ensiling process allows year-round biomanufacturing, minimal environmental-controlled storage, and reduces the industry need for multiple growth areas to maintain multi-product manufacturing of plant-based pharmaceuticals. This study shows that griffithsin can be expressed in N. excelsiana and is stable, recoverable, and active from ensiled tissue. These studies can pave the way for future plant-based pharmaceuticals to be expressed and stored in this manner.


ASE Statement on Point-of-Care Ultrasound (POCUS) During the 2019 Novel Coronavirus Pandemic


title: A novel and exploitable antifungal peptide from kale (Brassica alboglabra) seeds

text: The aim of this study was to purify and characterize antifungal peptides from kale seeds in view of the paucity of information on antifungal peptides from the family Brassicaceae, and to compare its characteristics with those of published Brassica antifungal peptides. A 5907-Da antifungal peptide was isolated from kale seeds. The isolation procedure comprised affinity chromatography on Affi-gel blue gel, ion exchange chromatography on SP-Sepharose and Mono S, and gel filtration on Superdex Peptide. The peptide was adsorbed on the first three chromatographic media. It inhibited mycelial growth in a number of fungal species including Fusarium oxysporum, Helminthosporium maydis, Mycosphaerella arachidicola and Valsa mali, with an IC(50) of 4.3 μM, 2.1 μM, 2.4 μM, and 0.15 μM, respectively and exhibited pronounced thermostability and pH stability. It inhibited proliferation of hepatoma (HepG2) and breast cancer (MCF7) cells with an IC(50) of 2.7 μM and 3.4 μM, and the activity of HIV-1 reverse transcriptase with an IC(50) of 4.9 μM. Its N-terminal sequence differed from those of antifungal proteins which have been reported to date.


title: Different residues in the SARS-CoV spike protein determine cleavage and activation by the host cell protease TMPRSS2

text: The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) mediates viral entry into target cells. Cleavage and activation of SARS S by a host cell protease is essential for infectious viral entry and the responsible enzymes are potential targets for antiviral intervention. The type II transmembrane serine protease TMPRSS2 cleaves and activates SARS S in cell culture and potentially also in the infected host. Here, we investigated which determinants in SARS S control cleavage and activation by TMPRSS2. We found that SARS S residue R667, a previously identified trypsin cleavage site, is also required for S protein cleavage by TMPRSS2. The cleavage fragments produced by trypsin and TMPRSS2 differed in their decoration with N-glycans, suggesting that these proteases cleave different SARS S glycoforms. Although R667 was required for SARS S cleavage by TMPRSS2, this residue was dispensable for TMPRSS2-mediated S protein activation. Conversely, residue R797, previously reported to be required for SARS S activation by trypsin, was dispensable for S protein cleavage but required for S protein activation by TMPRSS2. Collectively, these results show that different residues in SARS S control cleavage and activation by TMPRSS2, suggesting that these processes are more complex than initially appreciated.


title: Development of reagents to study the turkey's immune response: Cloning and characterisation of two turkey cytokines, interleukin (IL)-10 and IL-13

text: Abstract The cDNAs of two turkey cytokines, interleukin (IL)-10 and IL-13, were cloned using oligonucleotide primers designed from their chicken orthologues. The coding regions of the chicken and turkey genes are highly conserved, with IL-10 and IL-13 exhibiting 94.1% and 90% nucleotide and 92% and 79.9% amino acid identity respectively. Both showed consistent mRNA expression in turkey lymphoid and gut tissues. Expression in non-lymphoid tissues was more variable but generally highest in the skin and trachea. Recombinant turkey IL-10 was expressed and bioactivity demonstrated by inhibition of IFN-γ synthesis from activated splenocytes. Chicken and turkey IL-10 cross-reacted in functional assays.


title: The technological 'exposure' of populations; characterisation and future reduction

text: The nature and level of individuals' exposure to technological systems has been explored previously and is briefly restated here. This paper demonstrates how the concept of technological exposure can be extended to generic needs of individuals, and further to the needs of populations of individuals and even as far as “existential threats” to humanity. Technological categories that incur high levels of population exposure are explored, and categories are described. A theoretical basis for reducing population exposure is developed from the basic concepts of technological exposure. Technological developments that potentially enable less centralised societies having lower levels of population exposure, are considered for practicality and effectiveness as are the factors that could allow and cause transition to a less technologically centralised model. Some conclusions regarding practicality, triggers, and issues arising from a decentralised society are considered and include the key conclusion that a higher level of decentralisation and exposure reduction is both desirable and possible.


title: Site specific target binding controls RNA cleavage efficiency by the Kaposi's sarcoma-associated herpesvirus endonuclease SOX

text: A number of viruses remodel the cellular gene expression landscape by globally accelerating messenger RNA (mRNA) degradation. Unlike the mammalian basal mRNA decay enzymes, which largely target mRNA from the 5′ and 3′ end, viruses instead use endonucleases that cleave their targets internally. This is hypothesized to more rapidly inactivate mRNA while maintaining selective power, potentially though the use of a targeting motif(s). Yet, how mRNA endonuclease specificity is achieved in mammalian cells remains largely unresolved. Here, we reveal key features underlying the biochemical mechanism of target recognition and cleavage by the SOX endonuclease encoded by Kaposi's sarcoma-associated herpesvirus (KSHV). Using purified KSHV SOX protein, we reconstituted the cleavage reaction in vitro and reveal that SOX displays robust, sequence-specific RNA binding to residues proximal to the cleavage site, which must be presented in a particular structural context. The strength of SOX binding dictates cleavage efficiency, providing an explanation for the breadth of mRNA susceptibility observed in cells. Importantly, we establish that cleavage site specificity does not require additional cellular cofactors, as had been previously proposed. Thus, viral endonucleases may use a combination of RNA sequence and structure to capture a broad set of mRNA targets while still preserving selectivity.


title: Roles for the Recycling Endosome, Rab8, and Rab11 in hantavirus release from epithelial cells

text: Hantavirus structural proteins are believed to localize to intracellular membranes often identified as Golgi membranes, in virus-infected cells. After virus budding into the Golgi luminal space, virus-containing vesicles are transported to the plasma membrane via trafficking pathways that are not well defined. Using the New World hantavirus, Andes virus, we have investigated the role of various Rab proteins in the release of hantavirus particles from infected cells. Rabs 8 and 11 were found to colocalize with Andes virus proteins in virus infected cells and when expressed from cDNA, implicating the recycling endosome as an organelle important for hantavirus infection. Small interfering RNA-mediated downregulation of Rab11a alone or Rab11a and Rab11b together resulted in a decrease in infectious virus particle secretion from infected cells. Downregulation of Rab8a did not alter infectious virus release but reduction of both isoforms did. These data implicate the recycling endosome and the Rab proteins associated with vesicular transport to or from this intracellular organelle as an important pathway for hantavirus trafficking to the plasma membrane.


title: Small interfering RNAs targeting the rabies virus nucleoprotein gene

text: Abstract Rabies virus (RABV) infection continues to be a global threat to human and animal health, yet no curative therapy has been developed. RNA interference (RNAi) therapy, which silences expression of specific target genes, represents a promising approach for treating viral infections in mammalian hosts. We designed six small interfering (si)RNAs (N473, N580, N783, N796, N799 and N1227) that target the conserved region of the RABV challenge virus standard (CVS)-11 strain nucleoprotein (N) gene. Using a plasmid-based transient expression model, we demonstrated that N796, N580 and N799 were capable of significantly inhibiting viral replication in vitro and in vivo. These three siRNAs effectively suppressed RABV expression in infected baby hamster kidney-21 (BHK-21) cells, as evidenced by direct immunofluorescence assay, viral titer measurements, real-time PCR, and Western blotting. In addition, liposome-mediated siRNA expression plasmid delivery to RABV-infected mice significantly increased survival, compared to a non-liposome-mediated delivery method. Collectively, our results showed that the three siRNAs, N796, N580 and N799, targeting the N gene could potently inhibit RABV CVS-11 reproduction. These siRNAs have the potential to be developed into new and effective prophylactic anti-RABV drugs.


title: In-silico strategies for probing chloroquine based inhibitors against SARS-CoV-2

text: The global health emergency of novel COVID-19 is due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Currently there are no approved drugs for the treatment of coronaviral disease (COVID-19), although some of the drugs have been tried. Chloroquine is being widely used in treatment of SARS-CoV-2 infection. Hydroxychloroquine, the derivative of Chloroquine shows better inhibition than Chloroquine and has in vitro activity against SARS-CoV-2 also used to treat COVID-19. To study the interactions of Chloroquine and derivatives of Chloroquine with SARS-CoV-2, series of computational approaches like pharmacophore model, molecular docking, MM_GBSA study and ADME property analysis are explored. The pharmacophore model and molecular docking study are used to explore the structural properties of the compounds and the ligand-receptor (PDB_ID: 6LU7) interactions respectively. MM_GBSA study gives the binding free energy of the protein-ligand complex and ADME property analysis explains the pharmacological property of the compounds. The resultant best molecule (CQD15) further subjected to molecular dynamics (MD) simulation study which explains the protein stability (RMSD), ligand properties as well as protein-ligand contacts. Outcomes of the present study conclude with the molecule CQD15 which shows better interactions for the inhibition of SARS-CoV-2 in comparison to Chloroquine and Hydroxychloroquine. Communicated by Ramaswamy H. Sarma


title: Potential Therapeutic Targeting of Coronavirus Spike Glycoprotein Priming

text: Processing of certain viral proteins and bacterial toxins by host serine proteases is a frequent and critical step in virulence. The coronavirus spike glycoprotein contains three (S1, S2, and S2′) cleavage sites that are processed by human host proteases. The exact nature of these cleavage sites, and their respective processing proteases, can determine whether the virus can cross species and the level of pathogenicity. Recent comparisons of the genomes of the highly pathogenic SARS-CoV2 and MERS-CoV, with less pathogenic strains (e.g., Bat-RaTG13, the bat homologue of SARS-CoV2) identified possible mutations in the receptor binding domain and in the S1 and S2′ cleavage sites of their spike glycoprotein. However, there remains some confusion on the relative roles of the possible serine proteases involved for priming. Using anthrax toxin as a model system, we show that in vivo inhibition of priming by pan-active serine protease inhibitors can be effective at suppressing toxicity. Hence, our studies should encourage further efforts in developing either pan-serine protease inhibitors or inhibitor cocktails to target SARS-CoV2 and potentially ward off future pandemics that could develop because of additional mutations in the S-protein priming sequence in coronaviruses.


title: A novel method for high-throughput screening to quantify antiviral activity against viruses that induce limited CPE

text: Abstract For antiviral screenings purposes, infection of cell cultures with the virus under study, should ideally result in the induction, within just a few days, of (nearly) complete CPE and allow the calculation of acceptable Z’ factors (>0.5). The human Corona virus NL63 (HCoV-NL63) causes only limited CPE on different cell lines (Schildgen et al., 2006). Following infection of Vero118 cells, virus-induced CPE was too low to allow readout based on classical colorimetric methods (such as the MTS assay), even following prolonged incubation times (>7 days). To develop an antiviral screenings-assay against HCoV-NL63, we explored whether a dead-cell protease substrate could be used instead. The substrate used is a quenched peptide (bis-AAF-R110) that releases a fluorophore upon proteolytic-cleavage by proteases; the latter released from dead cells. Following different rounds of optimization a screening protocol was developed: Vero118 cells in 96-well plate format were infected with HCoV-NL63 (MOI=0.01; 200μL cell culture; 2.104 cells/mL, IMDM 5% FBS medium). Cultures were subsequently incubated for 5 days at 35°C after which 20μL of the peptide solution was added. Fluorescence was quantitated 2 hr after incubation at 37°C. A roughly 3-fold increase in fluorescence intensity in the infected cultures was observed as compared to the uninfected cultures with a low well-to-well variability. Z’ factors calculated from different experiments were in the range of 0.6–0.8, indicating excellent assay quality. An anti-ACE2 polyclonal antiserum (that prevents coronavirus infection in cell cultures) was used as a positive control and allowed to validate the assay for antiviral screening purposes. In conclusion, in conditions where a viability staining is inadequate to quantitate virus-induced CPE, a novel simple and convenient method that detects cell-death and that is suitable for high-throughput screening purposes can be employed.


title: New method for the visual detection of human respiratory syncytial virus using reverse transcription loop-mediated amplification

text: Abstract Human respiratory syncytial virus (HRSV) is a seasonal respiratory pathogen that causes respiratory infection in children and the elderly. A new, reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) assay was developed for the rapid (within 1h), simultaneous detection of A and B group HRSV. Primers specific for groups A and B were designed to amplify the N and L genes of HRSV, respectively. A fluorescent dye, calcein, was used as an indicator for the endpoint visual detection and/or real-time amplification of HRSV RNA. The detection limit of the new method was 281.17 50% tissue culture infective doses (TCID50)/ml for HRSV A and 1.58 TCID50/ml for HRSV B. To evaluate the validity of this method, a comparison with RT-PCR was performed using 77 nasopharyngeal swabs as samples. Both RT-LAMP and RT-PCR detected HRSV in 38 HRSV samples, yielding a positive rate of 49%. Of the RT-LAMP positive samples, 36 (95%) were also positive by RT-PCR, while two were negative by RT-PCR. Among the 36 RT-LAMP and RT-PCR positive samples, 11 belonged to HRSV group A, while 25 belonged to group B. The results show that the new RT-LAMP is simple, rapid and well suited for HRSV diagnosis, especially in a limited-resource setting.


Advanced forecasting of SARS‐CoV‐2‐related deaths in Italy, Germany, Spain, and New York State


title: Response to “The imaginary ‘Asian Super Consumer’: A critique of demand reduction campaigns for the illegal wildlife trade”

text: Abstract In a recent paper in Geoforum, Margulies et al. (2019) outline what they perceive as a bias toward an “Asian super consumer”. They argue that wildlife trade demand reduction campaigns are unfocused, untargeted, and therefore have a tendency to place blame on people of colour and communities in the Global South as key actors in driving illegal wildlife trade. As researchers and practitioners, we have been studying the demand for wildlife and wildlife products for many years. While we agree that it is vitally important to consider the cultural nuances of illegal and unsustainable wildlife trade and to operate in a manner that is respectful toward different cultures, we believe that the authors have overlooked the fact that modern wildlife trade demand reduction campaigns are already conducting this research and using it to target their campaigns to specific groups.


title: The interferon stimulated gene 20 protein (ISG20) is an innate defense antiviral factor that discriminates self versus non-self translation

text: ISG20 is a broad spectrum antiviral protein thought to directly degrade viral RNA. However, this mechanism of inhibition remains controversial. Using the Vesicular Stomatitis Virus (VSV) as a model RNA virus, we show here that ISG20 interferes with viral replication by decreasing protein synthesis in the absence of RNA degradation. Importantly, we demonstrate that ISG20 exerts a translational control over a large panel of non-self RNA substrates including those originating from transfected DNA, while sparing endogenous transcripts. This activity correlates with the protein’s ability to localize in cytoplasmic processing bodies. Finally, these functions are conserved in the ISG20 murine ortholog, whose genetic ablation results in mice with increased susceptibility to viral infection. Overall, our results posit ISG20 as an important defense factor able to discriminate the self/non-self origins of the RNA through translation modulation.


title: Natural Products as Potential Leads Against Coronaviruses: Could They be Encouraging Structural Models Against SARS-CoV-2?

text: New coronavirus referred to SARS-CoV-2 has caused a worldwide pandemic (COVID-19) declared by WHO. Coronavirus disease 2019 (COVID-19) is an infectious disease with severe acute respiratory syndrome caused by coronavirus-2 (SARS-CoV-2). SARS-CoV-2 is akin to SARS-CoV, which was the causative agent of severe acute respiratory syndrome (SARS) in 2002 as well as to that of Middle East respiratory syndrome (MERS) in 2012. SARS-CoV-2 has been revealed to belong to Coronaviridiae family as a member of β-coronaviruses. It has a positive-sense single-stranded RNA with the largest RNA genome. Since its genomic sequence has a notable similarity to that of SARS-CoV, antiviral drugs used to treat SARS and MERS are now being also applied for COVID-19 treatment. In order to combat SARS-CoV-2, many drug and vaccine development studies at experimental and clinical levels are currently conducted worldwide. In this sense, medicinal plants and the pure natural molecules isolated from plants have been reported to exhibit significant inhibitory antiviral activity against SARS-CoV and other types of coronaviruses. In the present review, plant extracts and natural molecules with the mentioned activity are discussed in order to give inspiration to researchers to take these molecules into consideration against SARS-CoV-2.


title: Challenging times: ethics, nursing and the COVID‐19 pandemic

text: Globally nurses and midwives are working hard to detect cases of COVID‐19, to save lives or give comfort in the face of death, to educate themselves and the public about protective measures to stop the viral spread, while still caring for those not infected with the virus. In many countries nurses are working under virtual siege from this pandemic, with not enough resources or personal protective equipment, overwhelming numbers of patients, staff shortages, underprepared health systems and supply chain failures. Nurses and other health and emergency workers are suffering physical and emotional stress, and moral distress from conflicting professional values. They are faced with unpalatable and complex ethical issues in practice, with moral conflicts, high levels of acuity and patient deaths, and long working hours. A rising number of nurses are infected with SARS‐CoV‐2 or dying in the line of duty. Nurses need strong moral courage, stamina and resilience to work on the front lines of the pandemic, often while separated from their loved ones.


title: Investigation of nonlinear epidemiological models for analyzing and controlling the MERS outbreak in Korea

text: Abstract Much concern has arisen regarding serious epidemics due to the Middle East Respiratory Syndrome (MERS) coronavirus. The first MERS case of Korea was reported on 20 May 2015, and since then, the MERS outbreak in Korea has resulted in hundreds of confirmed cases and tens of deaths. Deadly infectious diseases such as MERS have significant direct and indirect social impacts, which include disease-induced mortality and economic losses. Also, a delayed response to the outbreak and underestimating its danger can further aggravate the situation. Hence, an analysis and establishing efficient strategies for preventing the propagation of MERS is a very important and urgent issue. In this paper, we propose a class of nonlinear susceptible-infectious-quarantined (SIQ) models for analyzing and controlling the MERS outbreak in Korea. For the SIQ based ordinary differential equation (ODE) model, we perform the task of parameter estimation, and apply optimal control theory to the controlled SIQ model, with the goal of minimizing the infectious compartment population and the cost of implementing the quarantine and isolation strategies. Simulation results show that the proposed SIQ model can explain the observed data for the confirmed cases and the quarantined cases in the MERS outbreak very well, and the number of the MERS cases can be controlled reasonably well via the optimal control approach.


Fellowship Training in Adult Cardiothoracic Anesthesiology – navigating the new educational landscape due to the coronavirus crisis


title: Understanding and Managing Zoonotic Risk in the New Livestock Industries

text: Background: In many parts of the world, livestock production is undergoing a process of rapid intensification. The health implications of this development are uncertain. Intensification creates cheaper products, allowing more people to access animal-based foods. However, some practices associated with intensification may contribute to zoonotic disease emergence and spread: for example, the sustained use of antibiotics, concentration of animals in confined units, and long distances and frequent movement of livestock. Objectives: Here we present the diverse range of ecological, biological, and socioeconomic factors likely to enhance or reduce zoonotic risk, and identify ways in which a comprehensive risk analysis may be conducted by using an interdisciplinary approach. We also offer a conceptual framework to guide systematic research on this problem. Discussion: We recommend that interdisciplinary work on zoonotic risk should take into account the complexity of risk environments, rather than limiting studies to simple linear causal relations between risk drivers and disease emergence and/or spread. In addition, interdisciplinary integration is needed at different levels of analysis, from the study of risk environments to the identification of policy options for risk management. Conclusion: Given rapid changes in livestock production systems and their potential health implications at the local and global level, the problem we analyze here is of great importance for environmental health and development. Although we offer a systematic interdisciplinary approach to understand and address these implications, we recognize that further research is needed to clarify methodological and practical questions arising from the integration of the natural and social sciences.


title: Ivermectin and COVID-19: Keeping Rigor in Times of Urgency

text: Ivermectin and Novel Coronavirus Disease (COVID-19): Keeping Rigor in Times of Urgency.


title: Cooperation between transmissible gastroenteritis coronavirus (TGEV) structural proteins in the in vitro induction of virus-specific antibodies

text: Abstract Following infection of haplotype defined NIH-miniswine with virulent transmissible gastroenteritis coronavirus (TGEV), isolated mesenteric lymph node CD4+ T-cells mounted a specific proliferative response against infectious or inactivated purified virus in secondary in vitro stimulation. A specific, dose-dependent response to the three major recombinant viral proteins: spike (S), membrane (M), and nucleoprotein (N), purified by affinity chromatography, was characterized. Induction of in vitro antibody synthesis was analyzed. The purified recombinant viral proteins induced the in vitro synthesis of neutralizing TGEV-specific antibodies when porcine TGEV-immune cells were stimulated with each of the combinations made with two of the major structural proteins: S+N, S+M, and to a minor extent with M+N, but not by the individual proteins. S-protein was dissociated from purified virus using NP-40 detergent and then micellar S-protein oligomers (S-rosettes) were formed by removing the detergent. These occurred preferentially by the association of more than 10 S-protein trimmers. These S-rosettes in collaboration with either N or M-proteins elicited TGEV-specific antibodies with titers up to 84 and 60%, respectively, of those induced by the whole virus. N-protein could be partially substituted by a 15-mer peptide that represents a T helper epitope previously identified in N-protein (Antón et al. (1995)). These results indicate that the induction of high levels of TGEV-specific antibodies requires stimulation by at least two viral proteins, and that optimum responses are induced by a combination of S-rosettes and the nucleoprotein.