title: Genetic architecture of host proteins interacting with SARS-CoV-2

text: Strategies to develop therapeutics for SARS-CoV-2 infection may be informed by experimental identification of viral-host protein interactions in cellular assays and measurement of host response proteins in COVID-19 patients. Identification of genetic variants that influence the level or activity of these proteins in the host could enable rapid ‘in silico’ assessment in human genetic studies of their causal relevance as molecular targets for new or repurposed drugs to treat COVID-19. We integrated large-scale genomic and aptamer-based plasma proteomic data from 10,708 individuals to characterize the genetic architecture of 179 host proteins reported to interact with SARS-CoV-2 proteins or to participate in the host response to COVID-19. We identified 220 host DNA sequence variants acting in cis (MAF 0.01–49.9%) and explaining 0.3–70.9% of the variance of 97 of these proteins, including 45 with no previously known protein quantitative trait loci (pQTL) and 38 encoding current drug targets. Systematic characterization of pQTLs across the phenome identified protein-drug-disease links, evidence that putative viral interaction partners such as MARK3 affect immune response, and establish the first link between a recently reported variant for respiratory failure of COVID-19 patients at the ABO locus and hypercoagulation, i.e. maladaptive host response. Our results accelerate the evaluation and prioritization of new drug development programmes and repurposing of trials to prevent, treat or reduce adverse outcomes. Rapid sharing and dynamic and detailed interrogation of results is facilitated through an interactive webserver (https://omicscience.org/apps/covidpgwas/).


title: Distinct Epitopes on CD13 Mediate Opposite Consequences for Cell Adhesion

text: CD13 is a membrane glycoprotein with aminopeptidase activity, expressed on several cell types, including myeloid cells (dendritic cells, monocytes, macrophages, neutrophils, etc.). CD13 participates in several functions such as proteolytic regulation of bioactive peptides, viral receptor, angiogenesis, and tumor metastasis. CD13 has also been proposed to participate in cell adhesion, as crosslinking of CD13 by certain CD13-specific antibodies induces homotypic aggregation of monocytes and heterotypic adhesion of monocytes to endothelial cells. We generated two monoclonal antibodies (mAbs C and E) that block homotypic aggregation of U-937 monocytic cells induced by CD13-specific mAb 452. Moreover, the mAbs cause detachment of cells whose aggregation was induced by CD13 crosslinking. Both mAbs also inhibit heterotypic adhesion of U-937 monocytes to endothelial cells. mAbs C and E recognize membrane CD13 but bind to epitopes different from that recognized by mAb 452. Crosslinking of CD13 by mAb C or E is required to inhibit adhesion, as monovalent Fab fragments are not sufficient. Thus, C and E antibodies recognize a distinct epitope on CD13, and binding to this epitope interferes with both CD13-mediated cell adhesion and enzymatic activity. These antibodies may represent important tools to study cell-cell interactions mediated by CD13 in physiological and pathological conditions.


title: A mild type of childhood Covid-19 - A case report

text: Abstract This case is about a 9-year-old child diagnosed with COVID-19, with a history of epidemiology; SARS-CoV-2 nucleic acids testing was positive, while chest CT examination was negative. The clinical classification was light. Nonetheless, isolation measures should still be taken to avoid infecting others.


title: Contagion effect of COVID‐19 outbreak: Another recipe for disaster on Indian economy

text: The global outbreak of COVID‐19 and subsequent lockdowns raises serious economic concern and havoc worldwide. This article tries to provide an economic perspective of COVID‐19 in India using some statistical figure of economic indicators. Analysis is based on the data collected for macro‐economy, travel & tourism, transportation, stock market, human capital and trade. Finding revel that India could experience a health debacle at present and excruciating economic contraction in the near future if the government is unable to execute a proper policy framework. Based on the discussion, a few policy suggestions have been presented to counter both health and economic crisis.


COVID‐19 and (hydroxy)chloroquine–azithromycin combination: Should we take the risk for our patients?


title: COVID-19 as a Viral Functional ACE2 Deficiency Disorder with ACE2 Related Multi-organ Disease

text: SARS-CoV-2, the agent of COVID-19, shares a lineage with SARS-CoV-1, and a common fatal pulmonary profile but with striking differences in presentation, clinical course, and response to treatment. In contrast to SARS-CoV-1 (SARS), COVID-19 has presented as an often bi-phasic, multi-organ pathology, with a proclivity for severe disease in the elderly and those with hypertension, diabetes and cardiovascular disease. Whilst death is usually related to respiratory collapse, autopsy reveals multi-organ pathology. Chronic pulmonary disease is underrepresented in the group with severe COVID-19. A commonality of aberrant renin angiotensin system (RAS) is suggested in the at-risk group. The identification of angiotensin-converting-enzyme 2 (ACE2) as the receptor allowing viral entry to cells precipitated our interest in the role of ACE2 in COVID-19 pathogenesis. We propose that COVID-19 is a viral multisystem disease, with dominant vascular pathology, mediated by global reduction in ACE2 function, pronounced in disease conditions with RAS bias toward angiotensin-converting-enzyme (ACE) over ACE2. It is further complicated by organ specific pathology related to loss of ACE2 expressing cells particularly affecting the endothelium, alveolus, glomerulus and cardiac microvasculature. The possible upregulation in ACE2 receptor expression may predispose individuals with aberrant RAS status to higher viral load on infection and relatively more cell loss. Relative ACE2 deficiency leads to enhanced and protracted tissue, and vessel exposure to angiotensin II, characterised by vasoconstriction, enhanced thrombosis, cell proliferation and recruitment, increased tissue permeability, and cytokine production (including IL-6) resulting in inflammation. Additionally, there is a profound loss of the “protective” angiotensin (1-7), a vasodilator with anti-inflammatory, anti-thrombotic, antiproliferative, antifibrotic, anti-arrhythmic, and antioxidant activity. Our model predicts global vascular insult related to direct endothelial cell damage, vasoconstriction and thrombosis with a disease specific cytokine profile related to angiotensin II rather than “cytokine storm”. Our proposed mechanism of lung injury provides an explanation for early hypoxia without reduction in lung compliance and suggests a need for revision of treatment protocols to address vasoconstriction, thromboprophylaxis, and to minimize additional small airways and alveolar trauma via ventilation choice. Our model predicts long term sequelae of scarring/fibrosis in vessels, lungs, renal and cardiac tissue with protracted illness in at-risk individuals. It is hoped that our model stimulates review of current diagnostic and therapeutic intervention protocols, particularly with respect to early anticoagulation, vasodilatation and revision of ventilatory support choices.


title: Neonatal immunity and immunisation in early age: lessons from veterinary medicine

text: Abstract The objective of this paper is to review adaptive immunity of young animals using examples from my own experience and from the literature. Trials carried out by us with a modified live and inactivated canine parvovirus vaccine in newborn puppies provide evidence of the immune capacity of these puppies. With regard to transfer of immunity from mother to offspring, there is a role for transplacental and colostral immunity. Examples of passive protection of young animals against different infections include passive protection of kittens against the feline immunodeficiency virus. However, passive immunity, though very useful at an early age, varies in duration and makes implementation of standard vaccination schedules difficult. Other experiments demonstrate that, under certain conditions, it is possible to overcome residual maternally-derived antibodies and to induce post-vaccinal immunity.


title: Patient Contact Recall after SARS Exposure

text: We reinterviewed healthcare workers who had been exposed to a patient with severe acute respiratory syndrome (SARS) in an intensive care unit to evaluate the effect of time on recall reliability and willingness to report contact activities and infection control precautions. Healthcare workers reliably recalled events 6 months after exposure.


title: Pause, Persist, Pivot: Key Decisions Health Professions Education Researchers Must Make About Conducting Studies During Extreme Events

text: When extreme events occur, some research becomes a clear priority, but what becomes of all other research? Does it stop indefinitely, or can it be paused with plans to resume, persist with modifications, or pivot to address new priorities? Facing this dilemma and witnessing it among their fellow health professions education researchers, the authors recognized a need for guidance. This Invited Commentary presents a framework, organized as key questions related to the research stage and process, to assist health professions education researchers in making decisions about how to proceed with research that was planned or in progress when an extreme event occurred. Although at the time of this writing, the COVID-19 pandemic was the extreme event at hand, the authors intentionally created questions and discussed considerations that can be helpful for thinking through decisions in a variety of disruptions in health professions education research—many of which require similar difficult decisions and creative solutions to carry important research forward and maintain high quality.


Cardiac involvement of COVID-19: Looking forward to novel discoveries and clinically valuable evidence()


title: It can be dangerous to take epidemic curves of COVID-19 at face value

text: During an epidemic with a new virus, we depend on modelling to plan the response: but how good are the data? The aim of our work was to better understand the impact of misclassification errors in identification of true cases of COVID-19 on epidemic curves. Data originated from Alberta, Canada (available on 28 May 2020). There is presently no information of sensitivity (Sn) and specificity (Sp) of laboratory tests used in Canada for the causal agent for COVID-19. Therefore, we examined best attainable performance in other jurisdictions and similar viruses. This suggested perfect Sp and Sn 60–95%. We used these values to re-calculate epidemic curves to visualize the potential bias due to imperfect testing. If the sensitivity improved, the observed and adjusted epidemic curves likely fall within 95% confidence intervals of the observed counts. However, bias in shape and peak of the epidemic curves can be pronounced, if sensitivity either degrades or remains poor in the 60–70% range. These issues are minor early in the epidemic, but hundreds of undiagnosed cases are likely later on. It is therefore hazardous to judge progress of the epidemic based on observed epidemic curves unless quality of testing is better understood. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.17269/s41997-020-00367-6) contains supplementary material, which is available to authorized users.


title: Lower respiratory tract respiratory virus infections increase the risk of invasive aspergillosis after a reduced-intensity allogeneic hematopoietic SCT

text: We have analyzed the incidence and risk factors for the occurrence of invasive aspergillosis (IA) among 219 consecutive recipients of an allogeneic hematopoietic SCT after a reduced-intensity conditioning regimen (Allo-RIC). Twenty-seven patients developed an IA at a median of 218 days (range 24–2051) post-Allo-RIC, for a 4-year incidence of 13% (95% confidence interval 4–24%). In multivariate analysis, risk factors for developing IA were steroid therapy for moderate-to-severe graft vs host disease (GVHD) (Hazard Ratio (HR) 2.9, P=0.03), occurrence of a lower respiratory tract infection (LRTI) by a respiratory virus (RV) (HR 4.3, P<0.01) and CMV disease (HR 2.8, P=0.03). Variables that decreased survival after Allo-RIC were advanced disease phase (HR 1.9, P=0.02), steroid therapy for moderate-to-severe GVHD (HR 2.2, P<0.01), not developing chronic GVHD (HR 4.3, P<0.01), occurrence of LRTI by an RV (HR 3.4, P<0.01) and CMV disease (HR 2, P=0.01), whereas occurrence of IA had no effect on survival (P=0.5). Our results show that IA is a common infectious complication after an Allo-RIC, which occurs late post-transplant and may not have a strong effect on survival. An important observation is the possible role of LRTI by conventional RVs as risk factors for IA.


title: Contextualizing green building rating systems: Case study of Hong Kong

text: The paper reports on a research study undertaken on the differentiation of green building certification systems at an international, national and local level. Through a cross comparison, authors are able to explain the differences by the contextualism theory which could be traced back to the fundamental divergence on lifestyles, preferences, urban morphology besides climatic variations. The discussion is derived from a study of three green rating systems representing international, national and local systems with reference to intentions, mechanisms and benchmarks to facilitate objective assessments. For the case of Hong Kong, local challenges are identified and compared with counterparts at a national level. Two residential projects having certified by the ‘modified, localized’ national system is selected for a case study for synopsis with a view to explain the cause and effect of transferability versus non-transferability of assessment credits and protocols. Introducing and applying national and international systems to a local context can detect flaws in local design practices that may be ignored in the local rating system.


title: Acute acral cutaneous manifestations during the COVID‐19 pandemic: a single center experience

text: Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome‐related coronavirus 2 (SARS‐CoV‐2), was first reported in China on December 2019. Almost 5 months into the pandemic, little is still known about cutaneous manifestations in COVID‐19. In fact, the prevalence of cutaneous signs varies greatly in the literature, ranging from 0.2% to 20.4%. Given their potential association with COVID‐19, acral lesions have received special attention worldwide, both in the medical literature and the media. Our aim is to share our experience regarding acral manifestations during this pandemic.


title: Prise en charge des pathologies respiratoires à adénovirus chez l’enfant immunocompétent À propos d’une étude rétrospective de 116 enfants hospitalisés

text: Résumé Les adénovirus sont une cause commune d’atteinte respiratoire ; bien que dépendant du sérotype, ils peuvent également être la cause d’atteintes extrarespiratoires. Le diagnostic positif peut en être difficile. Les résultats cliniques chez 116 enfants hospitalisés en raison d’une infection adénovirale ont été repris rétrospectivement. Chez 71 enfants, le diagnostic virologique a été obtenu par immunofluorescence directe sur les aspirations nasales, 71 par culture virale de ces mêmes prélèvements. Le tableau clinique de l’infection adénovirale est caractérisé par une fièvre élevée (moyenne 39°1C) et prolongée (durée moyenne 4,3 jours). L’atteinte des voies aériennes supérieures (rhinopharyngite, angine, otite) et des voies aériennes inférieures (bronchite, bronchiolite, pneumopathie) sont les plus fréquentes. Douze enfants ont présenté des convulsions hyperpyrétiques, 6 avaient une méningite lymphocytaire. Les examens complémentaires ont objectivé des valeurs allant de la normalité à celles évocatrices d’infection bactérienne. Cinquante-neuf enfants furent adressés pour fièvre résistante à une antibiothérapie. Les symptômes de l’atteinte respiratoire dues aux infections adénovirales s’étendent de la rhinite à la pneumopathie et la bronchiolite. Les adénovirus peuvent entraîner des séquelles graves même chez l’enfant sain. Les recherches sur les mécanismes moléculaires de l’infection virale sur les voies aériennes amèneront d’importantes voies de réflexion sur la nature des processus inflammatoires participant à l’asthme et à la bronchite chronique obstructive. La plupart des infections sont modérées et ne nécessitent qu’un traitement symptomatique. Il n’existe pas actuellement de traitement antiviral efficace pour les infections adénovirales graves. Le diagnostic virologique rapide par l’étude des sécrétions nasopharyngées est d’une grande utilité clinique. Abstract Adenoviruses most commonly cause respiratory illness; however, depending on the infecting serotype, they may also cause various other diseases. Diagnosis may be difficult to achieve. The clinical findings for 116 children hospitalised with adenoviral infection were studied retrospectively. In 71 children, the diagnosis was based on detection of adenovirus antigen in the nasopharyngeal specimens and in 71 children on viral culture. The clinical picture of adenoviral infection was characterised by high-grade (mean 39°1C) and prolonged fever (mean duration 4,3 days). Upper respiratory and lower respiratory symptoms were the most common infections. Twelve had been admitted to the hospital due to febrile convulsions, 6 had meningitis. Laboratory findings varied from normal values to values seen in bacterial infections. Thus it was difficult to distinguish adenoviral disease from a bacterial disease. Fifty-nine children were referred to the hospital due to infection unresponsive to antimicrobial therapy. Symptoms of respiratory infection caused by adenovirus may range from the common cold syndrome to pneumonia, croup and bronchiolitis. Adenoviruses can be responsible for severe consequences, even in previously healthy children. Studies of the molecular mechanisms of viral infections of the airways could provide important insights into the nature of the inflammatory process involved in asthma and chronic obstructive pulmonary disease. Most infections are mild and require no therapy or only symptomatic treatment. There are at present time no recognised antiviral agents that are effective in treating serious adenovirus disease. The rapid detection of adenovirus antigen in nasopharygeal specimens proved to have a great clinical value in the diagnosis.


title: Metastatic melanoma treatment with checkpoint inhibitors in the COVID‐19 era: experience from an Italian Skin Cancer Unit

text: Melanoma epidemiology has shown a constant increase in the last few decades even if mortality is low and only a small percentage of patients develop metastatic disease. For these patients, immunotherapy with checkpoint inhibitors (ICI) significantly improves disease outcome with a median survival more than 2 years. The same drugs are used as adjuvant treatment in disease-free patients. Coronavirus Disease-19 (COVID-19) is now a pandemic disease with lung manifestations, which can bring severe acute respiratory distress. The most important risk factors related to a higher death risk for COVID-19 pneumonia are elderly age and comorbidities (hypertension, diabetes, previous cancer).


title: Solid phase immune electron microscopy for diagnosis of transmissible gastroenteritis in pigs

text: A serological trapping technique is described for detecting transmissible gastroenteritis (tge) virus in faeces. The technique involves the coating of electron microscope grids with protein A and specific tge virus antiserum. Optimal conditions for performing this solid phase immune electron microscopy technique were a concentration 250 µg ml−1 of protein A; 1:100 diluted rabbit anti-tge virus hyperimmune serum for coating the grids and overnight incubation with virus samples. The possibility of detecting coronavirus in crude faeces was highly improved with solid phase immune electron microscopy, compared with conventional negative staining electron microscopy, by specific trapping of virus and prevention of adsorption of contaminants. The sensitivity of the method was evaluated by coded investigation of a dilution series of stock virus mixed with different pools of faeces. The improvement of virus detection in faeces by solid phase immune electron microscopy, compared with standard electron microscopy was at least 100-fold. Faecal shedding of coronavirus by pigs infected with virulent and attenuated strains of tge virus was studied. Virus detection in faeces by a standard electron microscopy technique was not practical, since the virus was obscured by a large quantity of debris in the faeces. By using solid phase immune electron microscopy, however, the aspect of the specimens on the grids improved so much that, in addition to more common immunofluorescence, the technique might be useful as a diagnostic test for tge. Virus was detected in daily faecal samples from one or two days after experimental infection with virulent tge virus, until death in five out of eight animals. Unlike immunofluorescence, solid phase immune electron microscopy may be used for diagnosis in living animals.


title: Planning for historic urban environments under austerity conditions: Insights from post-crash Ireland

text: In this paper, we examine how conservation-planning and local regeneration in historic urban cores have been re-shaped under austerity conditions and how local planners and local government more generally have negotiated or navigated this emerging austerity terrain. We seek to contribute to wider debates on ‘austerity urbanism’, by examining the impacts of austerity on local planning and how planning officials have attempted to moderate austerity largely imposed by central government (entrenched roll-back neoliberalism) but often through the further roll-out of neoliberalism in local growth strategies. Drawing on the experience of three Irish urban centres, we examine efforts to ‘sell’ the historic city. Both nationally and within the three case study areas, a common overarching theme was evident in the initial post-crisis response to urban development: an emphasis on utilising heritage as a potential economic regeneration pathway. However, while drawing on intangible heritage and heritage narratives for place-branding, the actual protection of tangible built heritage assets was undermined through a greater emphasis on ‘flexible’ planning responses to managing heritage, which seek to minimise barriers to development.


title: Applications of ultraviolet germicidal irradiation disinfection in health care facilities: Effective adjunct, but not stand-alone technology

text: This review evaluates the applicability and relative contribution of ultraviolet germicidal irradiation (UVGI) to disinfection of air in health care facilities. A section addressing the use of UVGI for environmental surfaces is also included. The germicidal susceptibility of biologic agents is addressed, but with emphasis on application in health care facilities. The balance of scientific evidence indicates that UVGI should be considered as a disinfection application in a health care setting only in conjunction with other well-established elements, such as appropriate heating, ventilating, and air-conditioning (HVAC) systems; dynamic removal of contaminants from the air; and preventive maintenance in combination with through cleaning of the care environment. We conclude that although UVGI is microbiocidal, it is not “ready for prime time” as a primary intervention to kill or inactivate infectious microorganisms; rather, it should be considered an adjunct. Other factors, such as careful design of the built environment, installation and effective operation of the HVAC system, and a high level of attention to traditional cleaning and disinfection, must be assessed before a health care facility can decide to rely solely on UVGI to meet indoor air quality requirements for health care facilities. More targeted and multiparameter studies are needed to evaluate the efficacy, safety, and incremental benefit of UVGI for mitigating reservoirs of microorganisms and ultimately preventing cross-transmission of pathogens that lead to health care-associated infections.


title: Exploration of Sialic Acid Diversity and Biology Using Sialoglycan Microarrays

text: Sialic acids (Sias) are a group of α‐keto acids with a nine‐carbon backbone, which display many types of modifications in nature. The diversity of natural Sia presentations is magnified by a variety of glycosidic linkages to underlying glycans, the sequences and classes of such glycans, as well as the spatial organization of Sias with their surroundings. This diversity is closely linked to the numerous and varied biological functions of Sias. Relatively large libraries of natural and unnatural Sias have recently been chemically/chemoenzymatically synthesized and/or isolated from natural sources. The resulting sialoglycan microarrays have proved to be valuable tools for the exploration of diversity and biology of Sias. Here we provide an overview of Sia diversity in nature, the approaches used to generate sialoglycan microarrays, and the achievements and challenges arising. © 2013 Wiley Periodicals, Inc. Biopolymers 99: 650–665, 2013.


title: Calicivirus from Novel Recovirus Genogroup in Human Diarrhea, Bangladesh

text: To identify unknown human viruses in the enteric tract, we examined 105 stool specimens from patients with diarrhea in Bangladesh. A novel calicivirus was identified in a sample from 1 patient and subsequently found in samples from 5 other patients. Phylogenetic analyses classified this virus within the proposed genus Recovirus.


Mechanical ventilation in COVID-19: Is it due to patient or virology factors?


title: Conducta práctica ante un niño febril al regresar de un viaje

text: Las enfermedades más frecuentes al regresar de un viaje al extranjero son las infecciones gastrointestinales, las enfermedades febriles y los problemas dermatológicos. La evaluación de un niño febril al regreso de un viaje es clínica: verificación de los antecedentes y las vacunaciones, búsqueda de otros casos en contacto, signos funcionales y físicos, y características del viaje. Unas pruebas complementarias de rutina completan a menudo la evaluación para una orientación sindrómica. Si bien las causas de fiebre son, sobre todo, cosmopolitas, la gravedad de la enfermedad exótica obliga a buscarlas prioritariamente. El paludismo debe sospecharse ante una fiebre procedente de África subsahariana. El diagnóstico se basa en la asociación de un frotis sanguíneo y una prueba sensible (gota gruesa, reacción en cadena de la polimerasa [PCR]) o una prueba de diagnóstico rápido (para Plasmodium falciparum). Los criterios clínico-biológicos de gravedad son esenciales para orientar y tratar al paciente. En caso de acceso no complicado por P. falciparum, el tratamiento se basa en un tratamiento combinado a base de artemisinina (ACT), arteméter-lumefantrina o artenimol-piperaquina. Los accesos graves se tratan con artesunato intravenoso, seguido de ACT oral. Dengue, chikungunya e infección por virus Zika tienen características clínicas comunes (fiebre-erupción-artralgias, tratamiento sintomático). En caso de dengue, conviene controlar la aparición de signos de alerta, que podrían hacer temer una evolución negativa. El chikungunya es grave en caso de transmisión en el parto, con un riesgo de encefalitis neonatal. En el niño, el Zika es asintomático o poco sintomático. Pero, en caso de infección durante el embarazo, el riesgo es el de una embriofetopatía. El diagnóstico de estas arbovirosis se basa en la PCR en la fase aguda y en la serología secundariamente. La sintomatología de la fiebre tifoidea es poco específica, lo cual justifica la práctica de hemocultivos sistemáticos ante una fiebre tras un viaje. Su tratamiento se basa en las cefalosporinas de tercera generación o el ciprofloxacino, pero las resistencias aumentan. En suma, la diversidad de las etiologías de una fiebre al regreso de un viaje y la potencial gravedad de las infecciones importadas imponen una reflexión sobre el proceso de tratamiento de estos pacientes, en especial en lo referente al riesgo de fiebre hemorrágica.


title: Italian Public Health Response to the COVID-19 Pandemic: Case Report from the Field, Insights and Challenges for the Department of Prevention

text: The coronavirus disease (COVID-19) outbreak is rapidly progressing globally, and Italy, as one of the main pandemic hotspots, may provide some hard lessons for other countries. In this paper, we summarize the current organizational capacity and provide a pragmatic and narrative account of strategies and activities implemented by the Department of Prevention (Dipartimento di Prevenzione)—the regional entity of the Local Health Authority of the Italian National Health Service in charge of public health—since the beginning of the outbreak. We conduct a preliminary analysis of general strengths, weaknesses, opportunities, and threats (SWOT) of the response strategies from a local perspective. Furthermore, we provide firsthand insights on future directions and priorities to manage this unprecedented pandemic. Our case report gives a qualitative view of the healthcare response, based on the experience of frontline professionals, with the aim to generate hypotheses about factors which may promote or hinder the prevention and management of a pandemic locally. We highlight the importance of a public health approach for responding to COVID-19 and reshaping healthcare systems.


title: A review of potential treatments to date in COVID-19 patients according to the stage of the disease

text: Abstract Introduction and motivation: Since the end of 2019, the COVID-19 pandemic has affected millions of people worldwide. With the rapid spread of this virus, an immense burden has fallen upon both healthcare and economic systems. As a consequence, there is an unprecedented urgency for researchers and scientific committees from all over the world to find an effective treatment and vaccine. Review Structure: Many potential therapies are currently under investigation, with some, like Hydroxychloroquine, being authorized for emergency use in some countries. The crucial issue is now clearly to find the suitable treatment strategy for patients given comorbidities and the timeline of the illness.Vaccines are also under development and phase 1 clinical trials are rolling. Despite all efforts, no single drug or vaccine has yet been approved. In this review, we aim at presenting the proposed pathophysiological mechanisms of SARS-CoV-2 and to provide clinicians with a brief and solid overview of the current potential treatments classified according to their use at the three different currently proposed disease stages. In light of pathogenesis and proposed clinical classification, this review’s purpose is to summarize and simplify the most important updates on the management and the potential treatment of this emergent disease.


title: Medicinal herb extracts ameliorate impaired growth performance and intestinal lesion of newborn piglets challenged with the virulent porcine epidemic diarrhea virus

text: The objective of this study was to evaluate effects of a combined use of extracts of medicinal herbs Taraxaumi mongolicum, Viola yedoensis Makino, Rhizoma coptidis, and Radix isatidis (MYCI) on porcine epidemic diarrhea (PED). Twenty-two 3-day-old piglets received an oral challenge with 3 × 10(3.5) TCID(50) of the virulent PED virus (PEDV) in PBS or PBS only and daily oral administration of 60 mg of the MYCI mixture suspended in milk replacer or the vehicle for 7 days in a 2 × 2 factorial arrangement of treatments. Average daily gain (ADG) increased (p < 0.05) in response to the MYCI treatment in the PEDV-challenged piglets (−18 vs. 7 g for the vehicle- vs. MYCI-administered group), but not in unchallenged animals (27 vs. 28 g). Diarrhea score and fecal PEDV shedding, however, were not influenced by the MYCI treatment. The PEDV challenge caused severe intestinal villus atrophy and crypt hyperplasia, both of which were alleviated by administration of the MYCI mixture as indicated by an increase in the villus height and a decrease in the crypt depth due to the treatment. Overall, medicinal herb extracts used in this study ameliorated impaired growth performance and intestinal lesion of newborn piglets challenged with the virulent PEDV. Therefore, our results suggest that the MYCI mixture could be used as a prophylactic or therapeutic agent against PED.


Pancitopenia en el curso de infección por SARS-CoV-2


title: Acute stroke management pathway during Coronavirus-19 pandemic

text: Since the outbreak of the COVID-19 epidemic which in our region, Veneto (Italy), dates back to February, we were confronted with several challenges, but with a constant aim of keeping our Stroke Unit COVID-free. For this reason, in addition to creating a dedicated hot-spot as a pre-triage just outside the Emergency Department, together with the Neuroradiology Unit we obtained a mobile CT unit that could be used by COVID-positive or COVID-suspected patients. Furthermore, thanks to the collaboration with colleagues from different specialties (Infectious Disease, Internal Medicine, Intensive Care, Emergency Medicine), dedicated areas for COVID patients were activated. This led to a substantial change of our acute stoke management pathway. As the number of COVID patients increased, and the WHO declared a state of pandemic, this new stroke pathway has been fully tested. We would like to share our experience and send a clear message to keep a high attention on stroke as an emergency condition, because we have observed a decreased number of patients with minor strokes and TIAs, longer onset-to-door and door-to-treatment times for major strokes, and a reduced number of transfers from spokes. We strongly believe that the general population and family doctors are rightly focused on COVID. However, to remain at home with stroke symptoms does not mean to “stay safe at home”.


title: Diversity of clinical appearance of cutaneous manifestations in the course of COVID‐19

text: The outbreak of COVID‐19 has stricken more than 203,000 people in Italy up to 30(th) of April 2020, with over 27,000 died according to official estimates(1). While Italy was one of the most affected countries in Europe, the impact of the disease in the southern part of the state was less dramatic than in the north, due to some still not understood reasons. Particularly in Sicily, ‘only’ 3,140 cases have been recorded, of whom 533 encountered in the province of Messina.


title: A second, non-canonical RNA-dependent RNA polymerase in SARS Coronavirus

text: In (+) RNA coronaviruses, replication and transcription of the giant ∼30 kb genome to produce genome- and subgenome-size RNAs of both polarities are mediated by a cognate membrane-bound enzymatic complex. Its RNA-dependent RNA polymerase (RdRp) activity appears to be supplied by non-structural protein 12 (nsp12) that includes an RdRp domain conserved in all RNA viruses. Using SARS coronavirus, we now show that coronaviruses uniquely encode a second RdRp residing in nsp8. This protein strongly prefers the internal 5′-(G/U)CC-3′ trinucleotides on RNA templates to initiate the synthesis of complementary oligonucleotides of <6 residues in a reaction whose fidelity is relatively low. Distant structural homology between the C-terminal domain of nsp8 and the catalytic palm subdomain of RdRps of RNA viruses suggests a common origin of the two coronavirus RdRps, which however may have evolved different sets of catalytic residues. A parallel between the nsp8 RdRp and cellular DNA-dependent RNA primases is drawn to propose that the nsp8 RdRp produces primers utilized by the primer-dependent nsp12 RdRp.


title: Scorpion Peptides: Potential Use for New Drug Development

text: Several peptides contained in scorpion fluids showed diverse array of biological activities with high specificities to their targeted sites. Many investigations outlined their potent effects against microbes and showed their potential to modulate various biological mechanisms that are involved in immune, nervous, cardiovascular, and neoplastic diseases. Because of their important structural and functional diversity, it is projected that scorpion-derived peptides could be used to develop new specific drugs. This review summarizes relevant findings improving their use as valuable tools for new drugs development.


title: Aetiology of Canine Infectious Respiratory Disease Complex and Prevalence of its Pathogens in Europe

text: Summary The canine infectious respiratory disease complex (CIRDC) is an endemic worldwide syndrome involving multiple viral and bacterial pathogens. Traditionally, Bordetella bronchiseptica (Bb), canine adenovirus type 2 (CAV-2), canine distemper virus (CDV), canine herpesvirus (CHV) and canine parainfluenza virus (CPiV) were considered the major causative agents. Lately, new pathogens have been implicated in the development of CIRDC, namely canine influenza virus (CIV), canine respiratory coronavirus (CRCoV), canine pneumovirus (CnPnV), Mycoplasma cynos and Streptococcus equi subspecies zooepidemicus. To better understand the role of the different pathogens in the development of CIRDC and their epidemiological relevance in Europe, prevalence data were collected from peer-reviewed publications and summarized. Evidence of exposure to Bb is frequently found in healthy and diseased dogs and client-owned dogs are as likely to be infected as kennelled dogs. Co-infections with viral pathogens are common. The findings confirm that Bb is an important cause of CIRDC in Europe. CAV-2 and CDV recovery rates from healthy and diseased dogs are low and the most likely explanation for this is control through vaccination. Seroconversion to CHV can be demonstrated following CIRDC outbreaks and CHV has been detected in the lower respiratory tract of diseased dogs. There is some evidence that CHV is not a primary cause of CIRDC, but opportunistically re-activates at the time of infection and exacerbates the disease. The currently available data suggest that CIV is, at present, neither a prevalent nor a significant pathogen in Europe. CPiV remains an important pathogen in CIRDC and facilitates co-infection with other viral and bacterial pathogens. CnPnV and CRCoV are important new elements in the aetiology of CIRDC and spread particularly well in multi-dog establishments. M. cynos is common in Europe and is more likely to occur in younger and kennelled dogs. This organism is frequently found together with other CIRDC pathogens and is significantly associated with more severe respiratory signs. S. zooepidemicus infection is not common and appears to be a particular problem in kennels. Protective immunity against respiratory diseases is rarely complete, and generally only a reduction in clinical signs and excretion of pathogen can be achieved through vaccination. However, even vaccines that only reduce and do not prevent infection carry epidemiological advantages. They reduce spread, increase herd immunity and decrease usage of antimicrobials. Recommending vaccination of dogs against pathogens of CIRDC will directly provide epidemiological advantages to the population and the individual dog.


title: Zymographic patterns of MMP-2 and MMP-9 in the CSF and cerebellum of dogs with subacute distemper leukoencephalitis

text: Abstract Distemper leukoencephalitis is a disease caused by the canine distemper virus (CDV) infection. It is a demyelinating disease affecting mainly the white matter of the cerebellum and areas adjacent to the fourth ventricle; the enzymes of the matrix metalloproteinases (MMPs) group, especially MMP-2 and MMP-9 have a key role in the myelin basic protein fragmentation and in demyelination, as well as in leukocyte traffic into the nervous milieu. To evaluate the involvement of MMPs during subacute distemper leukoencephalitis, we measured the levels of MMP-2 and MMP-9 by zymography in the cerebrospinal fluid (CSF) and in the cerebellum of 14 dogs naturally infected with CDV and 10 uninfected dogs. The infected dogs presented high levels of pro-MMP-2 in the CSF and elevated levels of pro-MMP-2 and pro-MMP-9 in the cerebellar tissue. Active MMP-2 was detected in the CSF of some infected dogs. As active MMP-2 and MMP-9 are required for cellular migration across the blood–brain barrier and any interference between MMPs and their inhibitors may result in an amplification of demyelination, this study gives additional support to the involvement of MMPs during subacute distemper leukoencephalitis and suggests that MMP-2 and MMP-9 may take part in the brain inflammatory changes of this disease.


title: Host-Viral Interactions: Role of Pattern Recognition Receptors (PRRs) in Human Pneumovirus Infections

text: Acute respiratory tract infection (RTI) is a leading cause of morbidity and mortality worldwide and the majority of RTIs are caused by viruses, among which respiratory syncytial virus (RSV) and the closely related human metapneumovirus (hMPV) figure prominently. Host innate immune response has been implicated in recognition, protection and immune pathological mechanisms. Host-viral interactions are generally initiated via host recognition of pathogen-associated molecular patterns (PAMPs) of the virus. This recognition occurs through host pattern recognition receptors (PRRs) which are expressed on innate immune cells such as epithelial cells, dendritic cells, macrophages and neutrophils. Multiple PRR families, including Toll-like receptors (TLRs), RIG-I-like receptors (RLRs) and NOD-like receptors (NLRs), contribute significantly to viral detection, leading to induction of cytokines, chemokines and type I interferons (IFNs), which subsequently facilitate the eradication of the virus. This review focuses on the current literature on RSV and hMPV infection and the role of PRRs in establishing/mediating the infection in both in vitro and in vivo models. A better understanding of the complex interplay between these two viruses and host PRRs might lead to efficient prophylactic and therapeutic treatments, as well as the development of adequate vaccines.


title: The Canadian 2014 porcine epidemic diarrhoea virus outbreak: Important risk factors that were not considered in the epidemiological investigation could change the conclusions

text: The introduction and spread of porcine epidemic diarrhoea virus (PEDV) in North America resulted in significant death loss in the swine industry. As the industry learned how to manage this disease, many new risks were identified, including the potential for feed and feed ingredients to become contaminated and spread PEDV. In addition, biosecurity practices were reevaluated and strengthened throughout the industry. At the time of the outbreak epidemiologists did not understand, as well as they are understood today, all the risk factors that contribute to the spread of PEDV. As a result, the epidemiological investigations into the 2014 PEDV outbreak in eastern Canada may not have investigated all risk factors as thoroughly as they would be investigated today. In retrospect, many of the Bradford Hill criteria used to determine causation were not fulfilled. This review identifies risk factors that were not included in the 2014 epidemiology. If these risk factors were included in the epidemiology, the conclusions and determination of causation may have been different.


Maternal Mortality Among Women with COVID-19 Admitted to the Intensive Care Unit


title: Tracking the engraftment and regenerative capabilities of transplanted lung stem cells using fluorescent nanodiamonds

text: Lung stem/progenitor cells are potentially useful for regenerative therapy, for example in repairing damaged or lost lung tissue in patients. Several optical imaging methods and probes have been used to track how stem cells incorporate and regenerate themselves in vivo over time. However, these approaches are limited by photobleaching, toxicity and interference from background tissue autofluorescence. Here we show that fluorescent nanodiamonds, in combination with fluorescence-activated cell sorting, fluorescence lifetime imaging microscopy and immunostaining, can identify transplanted CD45(–)CD54(+)CD157(+) lung stem/progenitor cells in vivo, and track their engraftment and regenerative capabilities with single-cell resolution. Fluorescent nanodiamond labelling did not eliminate the cells’ properties of self-renewal and differentiation into type I and type II pneumocytes. Time-gated fluorescence imaging of tissue sections of naphthalene-injured mice indicates that the fluorescent nanodiamond-labelled lung stem/progenitor cells preferentially reside at terminal bronchioles of the lungs for 7 days after intravenous transplantation. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nnano.2013.147) contains supplementary material, which is available to authorized users.


title: Specific organization for in‐hospital belatacept infusion to avoid nosocomial transmission during the SARS‐CoV‐2 pandemic

text: The first cases of Severe Acute Respiratory Syndrome coronavirus 2 (SARS‐CoV‐2) occurred in France in early February and in our region (Southwest France) in early March 2020.


title: Meeting report on 3rd National Congress of the Italian society of virology (SIV)

text: J. Cell. Physiol. 199: 171–173, 2004© 2004 Wiley‐Liss, Inc.


title: A rational roadmap for SARS‐CoV‐2/COVID‐19 pharmacotherapeutic research and development. IUPHAR Review 29

text: In this review, we identify opportunities for drug discovery in the treatment of COVID‐19 and in so doing, provide a rational roadmap whereby pharmacology and pharmacologists can mitigate against the global pandemic. We assess the scope for targetting key host and viral targets in the mid‐term, by first screening these targets against drugs already licensed; an agenda for drug re‐purposing, which should allow rapid translation to clinical trials. A simultaneous, multi‐pronged approach using conventional drug discovery methodologies aimed at discovering novel chemical and biological means targetting a short‐list of host and viral entities should extend the arsenal of anti‐SARS‐CoV‐2 agents. This longer‐term strategy would provide a deeper pool of drug choices for future‐proofing against acquired drug resistance. Second, there will be further viral threats, which will inevitably evade existing vaccines. This will require a coherent therapeutic strategy which pharmacology and pharmacologists are best placed to provide.


title: Application of the phosphoramidate ProTide approach to the antiviral drug ribavirin

text: Ribavirin is a nucleoside analogue with broad antiviral activity. Here we report the synthesis and biological evaluation of novel ribavirin ProTides designed to deliver the bioactive ribavirin monophosphate into cells. Some of the compounds display activity similar to the parent nucleoside against a range of viruses. Enzymatic, cell lysate and preliminary modeling studies have been performed to investigate the lack of enhancement of potency by the ProTides, and these indicate a failure at the final, amino acid cleavage step in the ProTide activation process, leading to inefficient release of the nucleoside monophosphate.


title: Epidemiological investigation of the 119th confirmed Middle East Respiratory Syndrome coronavirus case with an indefinite mode of transmission during the Pyeongtaek outbreak in Korea

text: Since the first case was diagnosed on May 20, 2015, there were 186 confirmed cases of Middle East Respiratory Syndrome (MERS) until the end of outbreak in South Korea. Although medical institutions were the most identifiable sources of MERS transmission in South Korea, similar to other countries, in-depth epidemiological investigation was required for some confirmed cases with indefinite contact history or hospital visit records. The subject of epidemiological investigation in the present study was a 35 year-old male patient diagnosed with MERS (#119) who lived in Asan-city and worked in Pyeongtaek-city. Various potential sources of transmission were carefully investigated. While he could have been exposed to MERS through a friend from Saudi Arabia or confirmed MERS cases in his workplace, neighboring areas, and medical institutions, as well as contacts in his home, the chances of transmission were low; however, the potential for transmission through his local community could not be excluded. Practically, it was difficult to determine the modes of transmission for all outbreak cases in communicable disease that occurred in this short period of time. The investigation to identify the mode of transmission in this case was ultimately unsuccessful. However, the various data collected and analyzed to reveal modes of transmission provided detailed information that could not be collected using only interview surveys.


title: Virucidal effect against Coronavirus SARS-CoV-2 of a silver nanocluster/silica composite sputtered coating

text: Abstract During the current pandemic of COVID-19 caused by the new Coronavirus SARS-CoV-2, the confinement measures slowed down the contagion, but did not completely avoid the disease diffusion for health workers, patients and the remaining population. The individual protection equipment (e.g. facial masks), filters for air conditioning systems and for medical respiratory devices do not possess an intrinsic antimicrobial/virucidal action and they are susceptible to microbial/viral colonization. An efficient antimicrobial/virucidal technology on air filtering media is crucial for maintaining a safe air environment and protecting people, in particular when lockdown is eased. This short communication reports about the virucidal effect, preliminary verified towards Coronavirus SARS-CoV-2, of a silver nanocluster/silica composite sputtered coating, directly applicated on a FFP3 mask.


title: Neurobiology of coronaviruses: Potential relevance for COVID-19

text: In the first two decades of the 21st century, there have been three outbreaks of severe respiratory infections caused by highly pathogenic coronaviruses (CoVs) around the world: the severe acute respiratory syndrome (SARS) by the SARS-CoV in 2002–2003, the Middle East respiratory syndrome (MERS) by the MERS-CoV in June 2012, and Coronavirus Disease 2019 (COVID-19) by the SARS-CoV-2 presently affecting most countries In all of these, fatalities are a consequence of a multiorgan dysregulation caused by pulmonary, renal, cardiac, and circulatory damage; however, COVID patients may show significant neurological signs and symptoms such as headache, nausea, vomiting, and sensory disturbances, the most prominent being anosmia and ageusia. The neuroinvasive potential of CoVs might be responsible for at least part of these symptoms and may contribute to the respiratory failure observed in affected patients. Therefore, in the present manuscript, we have reviewed the available preclinical evidence on the mechanisms and consequences of CoVs-induced CNS damage, and highlighted the potential role of CoVs in determining or aggravating acute and long-term neurological diseases in infected individuals. We consider that a widespread awareness of the significant neurotropism of CoVs might contribute to an earlier recognition of the signs and symptoms of viral-induced CNS damage. Moreover, a better understanding of the cellular and molecular mechanisms by which CoVs affect CNS function and cause CNS damage could help in planning new strategies for prognostic evaluation and targeted therapeutic intervention.


title: Successful blood glucose management of a severe COVID-19 patient with diabetes: A case report

text: RATIONALE: Coronavirus disease 2019 (COVID-19) has emerged as a rapidly spreading communicable disease affecting individuals worldwide. Patients with diabetes are more vulnerable to the disease, and the mortality is higher than in those without diabetes. We reported a severe COVID-19 patient with diabetes and shared our experience with blood glucose management. PATIENT CONCERNS: A 64-year-old female diabetes patient was admitted to the intensive care unit due to productive coughing for 8 days without any obvious cause. The results of blood gas analysis indicated that the partial pressure of oxygen was 84 mm Hg with oxygen 8 L/min, and the oxygenation index was less than 200 mm Hg. In addition, postprandial blood glucose levels were abnormal (29.9 mmol/L). DIAGNOSES: The patient was diagnosed with COVID-19 (severe type) and type 2 diabetes. INTERVENTIONS: Comprehensive interventions including establishing a multidisciplinary team, closely monitoring her blood glucose level, an individualized diabetes diet, early activities, psychological care, etc, were performed to control blood glucose while actively treating COVID-19 infection. OUTCOMES: After the comprehensive measures, the patient's blood glucose level gradually became stable, and the patient was discharged after 20 days of hospitalization. LESSONS: This case indicated that the comprehensive measures performed by a multidisciplinary team achieved good treatment effects on a COVID-19 patient with diabetes. Targeted treatment and nursing methods should be performed based on patients’ actual situations in clinical practice.


title: Quels éléments président à l’émergence d’une épidémie virale ? Peut-on la prévoir ?

text: Résumé L’émergence d’une maladie virale résulte le plus souvent d’un déséquilibre dans l’interaction entre l’agent infectieux, l’hôte et l’environnement. Après une phase d’introduction de la maladie virale dans un territoire ou une population donnée et une fois que les premières chaînes de transmission sont en place, on peut assister à la diffusion de la maladie, voire sa pérennisation si les mesures de contrôle ne sont pas mises en œuvre ou ne sont pas suffisamment efficaces. S’il est difficile d’anticiper la survenue et l’introduction d’une maladie virale émergente, les trois axes suivants de lutte doivent être développés pour en limiter l’impact : (1) anticipation et préparation ; (2) recherche et (3) veille et surveillance. Pour garantir enfin que les mesures prises soient pertinentes au regard des données disponibles et acceptables par la population, il convient de s’appuyer de manière systématique sur une approche multidisciplinaire qui devra être réévaluée de manière dynamique. Summary The emergence of a viral disease most often results from an imbalance in the interaction between the infectious agent, the host and the environment. After the introduction phase of a viral disease in a territory or a given population and once the first chains of transmission occur, the spread of the disease or its sustainability are possible if the control measures are not implemented or are not sufficiently effective. If it is difficult to anticipate the occurrence and introduction of an emerging viral disease, the following three key elements must be strengthened to limit its impact: (1) anticipation and preparation; (2) research and (3) monitoring and surveillance. Finally, to guarantee that the measures taken are relevant and acceptable to the population, a multidisciplinary approach must be systematically relied upon and re-evaluated on a prospective basis.


COVID-19: affordable alternatives of household disinfectants for community


title: Phylogenetic nomenclature and evolution of mannose-binding lectin (MBL2) haplotypes

text: BACKGROUND: Polymorphisms of the mannose-binding lectin gene (MBL2) affect the concentration and functional efficiency of the protein. We recently used haplotype-specific sequencing to identify 23 MBL2 haplotypes, associated with enhanced susceptibility to several diseases. RESULTS: In this work, we applied the same method in 288 and 470 chromosomes from Gabonese and European adults, respectively, and found three new haplotypes in the last group. We propose a phylogenetic nomenclature to standardize MBL2 studies and found two major phylogenetic branches due to six strongly linked polymorphisms associated with high MBL production. They presented high Fst values and were imbedded in regions with high nucleotide diversity and significant Tajima's D values. Compared to others using small sample sizes and unphased genotypic data, we found differences in haplotyping, frequency estimation, Fu and Li's D* and Fst results. CONCLUSION: Using extensive testing for selective neutrality, we confirmed that stochastic evolutionary factors have had a major role in shaping this polymorphic gene worldwide.


title: Microarray-based method for screening of immunogenic proteins from bacteria

text: BACKGROUND: Detection of immunogenic proteins remains an important task for life sciences as it nourishes the understanding of pathogenicity, illuminates new potential vaccine candidates and broadens the spectrum of biomarkers applicable in diagnostic tools. Traditionally, immunoscreenings of expression libraries via polyclonal sera on nitrocellulose membranes or screenings of whole proteome lysates in 2-D gel electrophoresis are performed. However, these methods feature some rather inconvenient disadvantages. Screening of expression libraries to expose novel antigens from bacteria often lead to an abundance of false positive signals owing to the high cross reactivity of polyclonal antibodies towards the proteins of the expression host. A method is presented that overcomes many disadvantages of the old procedures. RESULTS: Four proteins that have previously been described as immunogenic have successfully been assessed immunogenic abilities with our method. One protein with no known immunogenic behaviour before suggested potential immunogenicity. We incorporated a fusion tag prior to our genes of interest and attached the expressed fusion proteins covalently on microarrays. This enhances the specific binding of the proteins compared to nitrocellulose. Thus, it helps to reduce the number of false positives significantly. It enables us to screen for immunogenic proteins in a shorter time, with more samples and statistical reliability. We validated our method by employing several known genes from Campylobacter jejuni NCTC 11168. CONCLUSIONS: The method presented offers a new approach for screening of bacterial expression libraries to illuminate novel proteins with immunogenic features. It could provide a powerful and attractive alternative to existing methods and help to detect and identify vaccine candidates, biomarkers and potential virulence-associated factors with immunogenic behaviour furthering the knowledge of virulence and pathogenicity of studied bacteria.


title: Analysis of dsDNA and RNA viromes in methanogenic digesters reveals novel viral genetic diversity

text: Although viruses are not the key players of the anaerobic digestion process, they may affect the dynamics of bacterial and archaeal populations involved in biogas production. Until now viruses have received very little attention in this specific habitat; therefore, as a first step towards their characterization, we optimized a virus filtration protocol from anaerobic sludge. Afterwards, to assess dsDNA and RNA viral diversity in sludge samples from nine different reactors fed either with waste water, agricultural residues or solid municipal waste plus agro‐food residues, we performed metagenomic analyses. As a result we showed that, while the dsDNA viromes (21 assigned families in total) were dominated by dsDNA phages of the order C audovirales, RNA viruses (14 assigned families in total) were less diverse and were for the main part plant‐infecting viruses. Interestingly, less than 2% of annotated contigs were assigned as putative human and animal pathogens. Our study greatly extends the existing view of viral genetic diversity in methanogenic reactors and shows that these viral assemblages are distinct not only among the reactor types but also from nearly 30 other environments already studied, including the human gut, fermented food, deep sea sediments and other aquatic habitats.


title: Impact of lockdown in COVID 19 on glycemic control in patients with type 1 Diabetes Mellitus

text: BACKGROUND AND AIMS: COVID 19 is a novel pandemic affecting globally. Although no reliable data suggests that patients of well controlled Type 1 Diabetes Mellitus (T1DM) being at increased risk of becoming severely ill with SARS-CoV2, but lockdown may impact patients with T1DM requiring regular medications and follow up. Hence this study was planned to see the impact of lockdown on glycemic control in patients with T1DM. METHODS: A cross sectional study was done in T1DM patients in whom a structured questionnaire was administered on follow up within 15 days after lockdown. Data regarding hypoglycemic and hyperglycemic episodes, Diabetic ketoacidosis (DKA), insulin dose missed, regular glucose monitoring, dietary compliance, physical activity, hospitalization during the phase of lockdown was taken. Average blood glucose and HbA1C of lockdown phase was compared with the readings of prelockdown phase. RESULTS: Out of 52 patients, 36.5% had hyperglycemic and 15.3% had hypoglycemic episodes. Insulin dose was missed in 26.9%, glucose monitoring not done routinely in 36.5% and 17.4% were not diet compliant during lockdown. Average blood glucose during lockdown phase was 276.9 ± 64.7 mg/dl as compared to 212.3 ± 57.9 mg/dl during prelockdown phase. Mean HbA1c value of lockdown (10 ± 1.5%) which was much higher that of pre lockdown (8.8 ± 1.3%) and the difference was statistically significant (p < 0.05). CONCLUSION: Glycemic control of T1DM patients has worsened mainly due to non availability of insulin/glucostrips during lockdown period. There is a need for preparedness in future so that complications can be minimised.


title: Ultrastructure of the replication sites of positive-strand RNA viruses

text: Abstract Positive strand RNA viruses replicate in the cytoplasm of infected cells and induce intracellular membranous compartments harboring the sites of viral RNA synthesis. These replication factories are supposed to concentrate the components of the replicase and to shield replication intermediates from the host cell innate immune defense. Virus induced membrane alterations are often generated in coordination with host factors and can be grouped into different morphotypes. Recent advances in conventional and electron microscopy have contributed greatly to our understanding of their biogenesis, but still many questions remain how viral proteins capture membranes and subvert host factors for their need. In this review, we will discuss different representatives of positive strand RNA viruses and their ways of hijacking cellular membranes to establish replication complexes. We will further focus on host cell factors that are critically involved in formation of these membranes and how they contribute to viral replication.


title: Putative roles of the CNF2 and CDTIII toxins in experimental infections with necrotoxigenic Escherichia coli type 2 (NTEC2) strains in calves

text: Abstract Newborn colostrum-restricted calves were orally inoculated with an Escherichia coli strain, identified originally as non-pathogenic, and into which the plasmid pVir was conjugally transferred. This resulted in diarrhea, intestinal lesions and extra-intestinal invasion, suggesting that factors affecting these pathogenic properties are located on pVir. In order to analyze the respective roles of the toxins CNF2 and CDTIII in the pathogenesis, colostrum-restricted calves were inoculated with isogenic mutants in the cnf2 and the cdt-III genes. The loss of cnf2 is associated with a reduction in the pathogenicity, since diarrhea does not occur in calves challenged, in spite of successful colonization of the intestine. Nevertheless, the mutant strain remains able to invade the bloodstream and to localize in the internal organs. Conversely, the calves inoculated with mutant in the cdt-III gene evolved in the same way as wild-type strain-inoculated calves with regard to clinical signs and macroscopic or microscopic lesions.


title: Cuidados enfermeros orientados a mitigar la transmisión del coronavirus en caso de positivos: una revisión narrativa

text: Resumen Objetivo: Esta revisión tiene como objetivo realizar un mapeado de evidencias científicas en cuidados enfermeros dirigidos a controlar infecciones por coronavirus. Método: Se llevó a cabo una búsqueda bibliográfica en las bases de datos Medline, CINAHL, Scopus y en la colección principal de la WOS, sin límite de fecha y a través de las palabras clave “transmission”, “infection”, “contagious”, “spreads”, “coronavirinae”, “coronavirus”, “covid 19”, “sars cov 2”, “nurses” y “nursing”. Inicialmente se identificaron 154 estudios y, tras seleccionarlos según criterios de elegibilidad, se incluyeron 16. Resultados: Entre las recomendaciones principales, según la evidencia disponible, se encuentran el intercambio de aire en las habitaciones como medida para reducir el riesgo de contagio entre pacientes; el refuerzo de medidas en unidades de cuidados intensivos; seguimiento de contactos de casos positivos; y una adecuada formación de los profesionales. Discusión y conclusiones: Los estudios incluidos en la revisión trataron sobre prácticas de prevención y control de contagios, analizando riesgos asociados a la exposición y enumerando acciones para evitar complicaciones en pacientes críticos. Se identificaron patrones de transmisión de casos, contactos y factores asociados. También se estudiaron los conocimientos y actitudes profesionales, mostrando la importancia de una buena formación para el control de infecciones, y de disponer de equipos suficientes y adecuadas infraestructuras. Las enfermeras son vectores importantes de propagación. A pesar de que la evidencia disponible sobre la efectividad de cuidados para evitar el contagio por SARS-CoV-2 es escasa, los estudios publicados sobre la prevención y control ante brotes anteriores por coronavirus son de considerable utilidad. Abstract Objective: This review aims to map scientific evidence in nursing care aimed at controlling coronavirus infections. Methods: A bibliographic search was conducted in the Medline, CINAHL, Scopus and WOS main databases, with no date limit and using the keywords "transmission", "infection", "contagious", "spreads", "coronavirinae", "coronavirus", "COVID 19", "sars cov 2", "nurses" and "nursing". Initially, 154 studies were identified and, after selecting them according to eligibility criteria, 16 were included. Results: Among the main recommendations according to the available evidence are air exchange in rooms as a measure to reduce the risk of infection among patients; reinforcement of measures in intensive care units; follow-up of positive case contacts; and adequate training of professionals. Discussion and conclusions: The studies included in the review addressed infection prevention and control practices by analyzing risks associated with exposure and listing actions to avoid complications in critically ill patients. Patterns of case transmission, contacts and associated factors were identified. Professional knowledge and attitudes were also studied, showing the importance of good infection control training, and of sufficient equipment and adequate infrastructure. Nurses are important vectors of spread. Although there is little evidence available on the effectiveness of care to prevent the spread of SARS-CoV-2, published studies on the prevention and control of previous outbreaks of coronavirus are of considerable value.


Et les virus respiratoires !


title: Neuroepidemiology and the epidemiology of viral infections of the nervous system

text: Abstract Viral infections result in a tremendous burden of neurologic illness worldwide. Although many viral etiologies of neurologic infectious disease have been recently controlled through vaccination and other public health measures, the emergence of new pathogens and the re-emergence of previously controlled pathogens remain significant global public health challenges. One of the fundamental bases for understanding the dynamics of viral nervous system infections is through epidemiology – the science of assessing patterns of disease in populations and the factors that influence these patterns. Neuroepidemiology is a discipline that applies epidemiologic principles and practices to neurologic disease. There are several characteristics of neurologic illness that necessitate the subdiscipline of neuroepidemiology. This chapter reviews some of the basic terms and concepts of neuroepidemiology, including epidemiologic analysis and studies. It then applies these concepts to infections of the nervous system, including encephalitis, aseptic meningitis, acute myelitis, prion diseases, and slow virus infections. The chapter then addresses the epidemiology of emerging and re-emerging viral neurologic diseases as well as the factors driving these emergences. The epidemiology of viral nervous system diseases will undoubtedly continue to change and expand, and as we gain a better understanding of this epidemiology and the pathophysiology of viral infections, this will hopefully lead to improved surveillance, diagnostic, treatment, and prevention strategies for these illnesses.


title: RNA interference as a therapeutic strategy for treating CNS disorders

text: RNA interference (RNAi) controls gene silencing in most living organisms. The potential clinical applications of RNAi represent a strategy with unsurpassed selectivity, with the ability to target multiple disease-related genes, independent of their perceived drugability. The design of highly selective and efficacious small interfering (siRNAs) and short hairpin RNAs (shRNAs) has become routine, owing to significant progress in modeling and chemistry. RNAi significantly downregulates gene expression and function both in vitro and in vivo, including in the brain. This essay highlights recent findings and how the pharmaceutical industry intends to apply RNAi for the treatment neuropsychiatric and other diseases. Section editors: David Sibley – National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, USA C. Anthony Altar – Psychiatric Genomics, Gaithersburg, USA Theresa Branchek – Lundbeck Research, Paramus, USA


Articles That May Change Your Practice: Infection Prevention and Control


Famotidine against SARS-CoV2: A hope or hype?


title: Aerodynamic Characteristics and RNA Concentration of SARS-CoV-2 Aerosol in Wuhan Hospitals during COVID-19 Outbreak

text: Background The ongoing outbreak of COVID-19 has spread rapidly and sparked global concern. While the transmission of SARS-CoV-2 through human respiratory droplets and contact with infected persons is clear, the aerosol transmission of SARS-CoV-2 has been little studied. Methods Thirty-five aerosol samples of three different types (total suspended particle, size segregated and deposition aerosol) were collected in Patient Areas (PAA) and Medical Staff Areas (MSA) of Renmin Hospital of Wuhan University (Renmin) and Wuchang Fangcang Field Hospital (Fangcang), and Public Areas (PUA) in Wuhan, China during COVID-19 outbreak. A robust droplet digital polymerase chain reaction (ddPCR) method was employed to quantitate the viral SARS-CoV-2 RNA genome and determine aerosol RNA concentration. Results The ICU, CCU and general patient rooms inside Renmin, patient hall inside Fangcang had undetectable or low airborne SARS-CoV-2 concentration but deposition samples inside ICU and air sample in Fangcang patient toilet tested positive. The airborne SARS-CoV-2 in Fangcang MSA had bimodal distribution with higher concentration than those in Renmin during the outbreak but turned negative after patients number reduced and rigorous sanitization implemented. PUA had undetectable airborne SARS-CoV-2 concentration but obviously increased with accumulating crowd flow. Conclusions Room ventilation, open space, proper use and disinfection of toilet can effectively limit aerosol transmission of SARS-CoV-2. Gathering of crowds with asymptomatic carriers is a potential source of airborne SARS-CoV-2. The virus aerosol deposition on protective apparel or floor surface and their subsequent resuspension is a potential transmission pathway and effective sanitization is critical in minimizing aerosol transmission of SARS-CoV-2.


title: Hyperacute multi-organ thromboembolic storm in COVID-19: a case report

text: Acute viral pneumonia, hypoxemic respiratory failure and severe inflammatory response are hallmarks of severe coronavirus disease 2019 (COVID-19). The COVID-19-associated inflammatory state may further lead to symptomatic thromboembolic complications despite prophylaxis. We report a 66-year-old female patient with post-mortem diagnosis of COVID-19 who presented progressive livedo racemosa, acute renal failure and myocardial injury, as well as an absence of respiratory symptoms. Transthoracic echocardiography showed severe spontaneous echo contrast in the right cardiac chambers and right-sided cardiac overload presumed to result from pulmonary microvascular thrombosis or embolism. d-dimer levels were increased. The patient developed an acute ischemic stroke and died 2 days following presentation despite therapeutic anticoagulation. Her predominantly thromboembolic presentation supports the concept of coronavirus infection of endothelial cells and hypercoagulability, or COVID-19 endotheliitis. The case we report highlights that COVID-19-associated hyperacute multi-organ thromboembolic storm may precede or present disproportionately to respiratory involvement. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11239-020-02173-w) contains supplementary material, which is available to authorized users.


HIV Epidemiology in Africa: Weak Variables and Tendentiousness Generate Wobbly Conclusions


title: Evaluation of multiple commercial molecular and conventional diagnostic assays for the detection of respiratory viruses in children

text: This study compares the performance of four commercial multiplex PCR assays (Resplex II Panel v2.0, Seeplex RV15, xTAG RVP and xTAG RVP Fast) and direct fluorescent antibody (DFA) staining and viral isolation. Seven hundred and fifty nasopharyngeal swabs were tested for 17 viral agents. In each assay, the sensitivity and specificity for each target were determined against a composite reference standard. Two hundred and eighty-eight out of 750 (38.4%) specimens were positive by DFA or viral isolation, while an additional 214 (28.5%) were positive by multiplex PCR, for a total positivity rate of 66.9%. Of 502 positive specimens, one virus was detected in 420 specimens (83.7%), two in 77 (15.3%), three in four (0.8%) and four in one case (0.2%). Compared with a composite reference standard, the inter-assay accuracy of the multiplex PCR assays varied, but all were superior to conventional diagnostic methods in detecting a broad range of respiratory viral agents in children. In addition, the sensitivity of two commercial assays, Resplex II Plus PRE and Seeplex Influenza A/B Subtyping, was determined relative to the Astra influenza Screen & Type assay for detection of influenza A viruses, including seasonal influenzas and pandemic H1N1 2009 influenza A virus. Using 75 positive and 55 negative nasopharyngeal swabs for influenza A by the Astra assay, the sensitivity of Seeplex and Resplex was 95.9% and 91.8%, respectively, with a specificity of 100% for both.


title: Timeliness of Nongovernmental versus Governmental Global Outbreak Communications

text: To compare the timeliness of nongovernmental and governmental communications of infectious disease outbreaks and evaluate trends for each over time, we investigated the time elapsed from the beginning of an outbreak to public reporting of the event. We found that governmental sources improved the timeliness of public reporting of infectious disease outbreaks during the study period.


title: Angiotensin-converting enzyme 2 in acute respiratory distress syndrome

text: Angiotensin-converting enzyme (ACE) and ACE2 are highly homologous metalloproteases that provide essential catalytic functions in the renin-angiotensin system (RAS). Angiotensin II is one key effector peptide of the RAS, inducing vasoconstriction and exerting multiple biological functions. ACE cleaves angiotensin I to generate angiotensin II, whereas ACE2 reduces angiotensin II levels. Accumulating evidence has demonstrated a physiological and pathological role of ACE2 in the cardiovascular systems. Intriguingly, the SARS coronavirus, the cause of severe acute respiratory syndrome (SARS), utilizes ACE2 as an essential receptor for cell fusion and in vivo infections. Moreover, recent studies have demonstrated that ACE2 protects murine lungs from acute lung injury as well as SARS-Spike protein-mediated lung injury, suggesting a dual role of ACE2 in SARS infections and protection from ARDS.


title: Antigenicity of the peplomer protein of infectious bronchitis virus

text: Abstract To study the antigenic structure of the peplomer protein of the avian coronavirus infectious bronchitis virus, fragments from the peplomer gene were generated by restriction-enzyme cleavage or by limited DNase digestion and inserted in the Escherichia coli expression plasrnid pEX (Stanley and Luzio, 1984). The antigenicity of the expression products was tested using a number of polyclonal antisera and monoclonal antibodies. The polyclonal antisera recognized different sets of epitopes in the 1162-residue sequence. The N-terminal region of one of the two subunits, S2, was recognized by all polyclonal sera and by two monoclonal antibodies. This clearly immunodominant region contains at least two adjacent or overlapping epitopes, one of which has been localized within 18 residues. The epitopes found as antigenic pEX expression products do not coincide with the regions in the S1 subunit that have been found to contain hypervariable sequences. We suggest that these regions constitute conformation dependent neutralization epitopes that cannot be detected in the pEX system. The relevance of our finclings for vaccine development is discussed.


title: Dermatological therapies with relevance to COVID‐19

text: SARS‐CoV‐2 is a novel single stranded RNA virus that has gripped humanity all over. It affects primarily the respiratory system, but is not limited to it, causing widespread involvement of many organ systems. The cases are still rising at an exponential rate and manifold trials are on to test different agents with the hope for potential limitation of spread and control of symptoms. Various classes of drugs have been tried; some with moderate success while many are yet to be proven to be of definite benefit. We have observed that the drugs used in dermatology practice are featured in more than a few of such studies. Here we wish to highlight the ones that we are familiar with, which has featured at some point, in the management of this very challenging pandemic. This article is protected by copyright. All rights reserved.


Back to the Basics: Diluted Bleach for COVID-19


Can dried blood spots (DBS) contribute to conducting comprehensive SARS‐CoV‐2 antibody tests?


title: Mining Social Media and Web Searches For Disease Detection

text: Web-based social media is increasingly being used across different settings in the health care industry. The increased frequency in the use of the Internet via computer or mobile devices provides an opportunity for social media to be the medium through which people can be provided with valuable health information quickly and directly. While traditional methods of detection relied predominately on hierarchical or bureaucratic lines of communication, these often failed to yield timely and accurate epidemiological intelligence. New web-based platforms promise increased opportunities for a more timely and accurate spreading of information and analysis. This article aims to provide an overview and discussion of the availability of timely and accurate information. It is especially useful for the rapid identification of an outbreak of an infectious disease that is necessary to promptly and effectively develop public health responses. These web-based platforms include search queries, data mining of web and social media, process and analysis of blogs containing epidemic key words, text mining, and geographical information system data analyses. These new sources of analysis and information are intended to complement traditional sources of epidemic intelligence. Despite the attractiveness of these new approaches, further study is needed to determine the accuracy of blogger statements, as increases in public participation may not necessarily mean the information provided is more accurate.


title: Upper respiratory tract infection and serum antibody responses in nursing home patients

text: Abstract Residents of a Veterans Administration nursing home care unit (NHCU) were observed for the development of upper respiratory tract infection (URI) during 12 consecutive months to determine the frequency of sporadic cases of outbreaks of URI and to characterize them clinically and by laboratory means. Fifty-nine episodes of URI occurred in 56 residents during the study period. Serologic testing or virus isolation proved or suggested an etiologic agent on 22 occasions. URI was more common in late Fall and Winter and was caused by various agents, including influenza, Mycoplasma pneumoniae, respiratory syncytial virus, and parainfluenza viruses. A minor outbreak of influenza B in February 1986 contrasted with previous cases of URI in that the patients had a higher mean temperature and abnormal breath sounds, and they were clinically sicker. This suggests that clinical and epidemiologic surveillance during the influenza season may allow the early recognition of influenza in elderly nursing home residents. Over a 4-year period 147 serum antibody responses after influenza infection or influenza vaccination were compiled. Antibody responses to individual influenza vaccine components were measured 75 to 90 days after vaccination. The geometric mean titer (GMT) and the percentage of samples with antibody levels ⩾ 1:40 were determined for each of the three antigenic subtypes on 3 consecutive years. The GMT to individual vaccine components was consistently greater than 1:40, except to influenza B/Singapore in 1984 and A/Chile and B/U.S.S.R. in 1985, when these subtypes were first included in the vaccine, suggesting the NHCU residents responded less vigorously to unfamiliar vaccine subtypes. In 1984 the GMT to A/Phillippines of unvaccinated NHCU residents without URI was surprisingly no different from the corresponding GMT of their vaccinated counterparts, raising the possibility that an influenza A/Phillippines outbreak in 1983 conferred herd immunity.


Scientific statement of the Chinese Society of Cardiology (CSC) on using of renin angiotensin system blockers in patients with cardiovascular disease and COVID-19


title: Transcriptional profiling of the spleen in progressive visceral leishmaniasis reveals mixed expression of type 1 and type 2 cytokine-responsive genes

text: BACKGROUND: The Syrian golden hamster (Mesocricetus aureus) has been used as a model to study infections caused by a number of human pathogens. Studies of immunopathogenesis in hamster infection models are challenging because of the limited availability of reagents needed to define cellular and molecular determinants. RESULTS: We sequenced a hamster cDNA library and developed a first-generation custom cDNA microarray that included 5131 unique cDNAs enriched for immune response genes. We used this microarray to interrogate the hamster spleen response to Leishmania donovani, an intracellular protozoan that causes visceral leishmaniasis. The hamster model of visceral leishmaniasis is of particular interest because it recapitulates clinical and immunopathological features of human disease, including cachexia, massive splenomegaly, pancytopenia, immunosuppression, and ultimately death. In the microarray a differentially expressed transcript was identified as having at least a 2-fold change in expression between uninfected and infected groups and a False Discovery Rate of <5%. Following a relatively silent early phase of infection (at 7 and 14 days post-infection only 8 and 24 genes, respectively, were differentially expressed), there was dramatic upregulation of inflammatory and immune-related genes in the spleen (708 differentially expressed genes were evident at 28 days post-infection). The differentially expressed transcripts included genes involved in inflammation, immunity, and immune cell trafficking. Of particular interest there was concomitant upregulation of the IFN-γ and interleukin (IL)-4 signaling pathways, with increased expression of a battery of IFN-γ- and IL-4-responsive genes. The latter included genes characteristic of alternatively activated macrophages. CONCLUSIONS: Transcriptional profiling was accomplished in the Syrian golden hamster, for which a fully annotated genome is not available. In the hamster model of visceral leishmaniasis, a robust and functional IFN-γ response did not restrain parasite load and progression of disease. This supports the accumulating evidence that macrophages are ineffectively activated to kill the parasite. The concomitant expression of IL-4/IL-13 and their downstream target genes, some of which were characteristic of alternative macrophage activation, are likely to contribute to this. Further dissection of mechanisms that lead to polarization of macrophages toward a permissive state is needed to fully understand the pathogenesis of visceral leishmaniasis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12865-014-0038-z) contains supplementary material, which is available to authorized users.


title: Analysis of the codon usage pattern in Middle East Respiratory Syndrome Coronavirus

text: Middle East Respiratory Syndrome Coronavirus (MERS-CoV), which first broken out in Jeddah in 2012, causes a severe acute respiratory illness with a high mortality rate. To better understand the molecular characteristics of isolated MERS-CoV genomes, we first analysed the codon usage pattern of the zoonotic MERS-CoV strains comprehensively to gain an insight into the mechanism of cross-species transmission. We found that MERS human/camel isolates showed a low codon usage bias. Both mutation and nature selection pressure have contributed to this low codon usage bias, with the former being the main determining factor. We also observed that gene function, evolution time and the different host species of the virus all contributed to the bias of MERS-CoV, to some extent. Additionally, the codon usage pattern of MERS-CoV isolates is different from other related Nidovirales viruses isolated from bats and hedgehogs. In the future, more epidemiological surveys are required to examine the factors that resulted in the emergence and outbreak of this virus.


title: Reproduction of postweaning multisystemic wasting syndrome (PMWS) in immunostimulated and non-immunostimulated 3-week-old piglets experimentally infected with porcine circovirus type 2 (PCV2)

text: Abstract Postweaning multisystemic wasting syndrome (PMWS) in swine is causally associated with the newly recognised pathogen, porcine circovirus type 2 (PCV2). In this study, 3-week-old SPF PCV2-seronegative piglets were inoculated intranasally with PCV2. The effect of immunostimulation on the induction of PMWS was investigated by immunisation with keyhole limpet hemocyanin (KLH) emulsified in incomplete Freunds adjuvant. The study was terminated 5 weeks after inoculation. While disease was not observed in the age-matched controls, two out of five non-immunised PCV2-infected piglets died on postinoculation day (PID) 21, and one was euthanized on PID 25 in moribund condition. These animals had appeared lethargic with persistent fever from PID 12 onwards. The euthanized pig appeared smaller than littermates and suffered from jaundice. At postmortem examination, gastric ulceration, icterus, and liver and thymus atrophy were observed. Furthermore, histological lesions of degenerating hepatocytes and hepatitis in combination with lymphoid depletion and syncytial cells in lymph nodes were consistent with the diagnosis of PMWS. One out of five immunostimulated PCV2-infected piglets was euthanized on PID 22 with convulsions after a period with wasting. This pig was lethargic from PID 14 onwards with persistent fever from PID 8 and transient dyspnoea. No differences in clinical signs, gross pathologic or histological findings were observed for the remaining non-immunostimulated and immunostimulated PCV2-infected piglets. All 10 PCV2-inoculated piglets seroconverted to PCV2 within 14 days after inoculation. By virus isolation, quantitative polymerase chain reaction (Q-PCR), and immunostaining of cryostat sections, it was demonstrated that lymphoid tissue contained abundant PCV2 antigen. Viral DNA load in serum samples was assessed by Q-PCR. All four PMWS-affected piglets had high levels of PCV2 DNA in serum, suggesting that there was a correlation between high levels of viral DNA in serum and the development of PMWS. In conclusion, infection with PCV2 caused PMWS in SPF piglets, however, the immunostimulation did not seem to play a critical role.


title: Conformation of an RNA pseudoknot

text: Abstract The structure of the 5′ GCGAUUUCUGACCGCUUUUUUGUCAG 3′ RNA oligonucleotide was investigated using biochemical and chemical probes and nuclear magnetic resonance spectroscopy. Formation of a pseudoknot is indicated by the imino proton spectrum. Imino protons are observed consistent with formation of two helical stem regions; nuclear Overhauser enhancements between imino protons show that the two stem regions stack to form a continuous helix. In the stem regions, nucleotide conformations (3′-endo, anti) and internucleotide distances, derived from two-dimensional correlated, spectroscopy and two-dimensional nuclear Overhauser effect spectra, are characteristic of A-form geometry. The data suggest minor distortion in helical stacking at the junctions of stems and loops. The model of the pseudoknot is consistent with the structure originally proposed by Pleij et al.


title: Cardiovascular implications of the COVID-19 pandemic: a global perspective

text: The Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), represents the pandemic of the century, with approximately 3.5 million cases and 250,000 deaths worldwide as of May 2020. Although respiratory symptoms usually dominate the clinical presentation, COVID-19 is now known to also have potentially serious cardiovascular consequences, including myocardial injury, myocarditis, acute coronary syndromes, pulmonary embolism, stroke, arrhythmias, heart failure, and cardiogenic shock. The cardiac manifestations of COVID-19 might be related to the adrenergic drive, systemic inflammatory milieu and cytokine-release syndrome caused by SARS-CoV-2, direct viral infection of myocardial and endothelial cells, hypoxia due to respiratory failure, electrolytic imbalances, fluid overload, and side effects of certain COVID-19 medications. COVID-19 has profoundly reshaped usual care of both ambulatory and acute cardiac patients, by leading to the cancellation of elective procedures and by reducing the efficiency of existing pathways of urgent care, respectively. Decreased utilization of healthcare services for acute conditions by non-COVID-19 patients has also been reported and attributed to concerns about acquiring in-hospital infection. Innovative approaches that leverage modern technologies to tackle the COVID-19 pandemic have been introduced, which include telemedicine, dissemination of educational material over social media, smartphone apps for case tracking, and artificial intelligence for pandemic modelling, among others. This article provides a comprehensive overview of the pathophysiology and cardiovascular implications of COVID-19, its impact on existing pathways of care, the role of modern technologies to tackle the pandemic, and a proposal of novel management algorithms for the most common acute cardiac conditions.


title: Inactivation of airborne viruses using a packed bed non-thermal plasma reactor

text: Outbreaks of airborne infectious diseases such as measles or severe acute respiratory syndrome can cause significant public alarm. Where ventilation systems facilitate disease transmission to humans or animals, there exists a need for control measures that provide effective protection while imposing minimal pressure differential. In the present study, viral aerosols in an airstream were subjected to non-thermal plasma (NTP) exposure within a packed-bed dielectric barrier discharge reactor. Comparisons of plaque assays before and after NTP treatment found exponentially increasing inactivation of aerosolized MS2 phage with increasing applied voltage. At 30 kV and an air flow rate of 170 standard liters per minute, a greater than 2.3 log reduction of infective virus was achieved across the reactor. This reduction represented ~2 log of the MS2 inactivated and ~0.35 log physically removed in the packed bed. Increasing the air flow rate from 170 to 330 liters per minute did not significantly impact virus inactivation effectiveness. Activated carbon-based ozone filters greatly reduced residual ozone, in some cases down to background levels, while adding less than 20 Pa pressure differential to the 45 Pa differential pressure across the packed bed at the flow rate of 170 standard liters per minute.


title: Emergency nurses’ perceptions regarding the risks appraisal of the threat of the emerging infectious disease situation in emergency departments

text: Purpose: Emerging infectious diseases are considered as a pressing challenge to global public health. Throughout public health response to emerging infectious diseases, emergency nurses are situated at the forefront of the healthcare system. The present study has explored emergency nurses’ perceptions regarding the risks appraisal of the threat of the emerging infectious disease situation in emergency department context. Methods: The present study used a qualitative descriptive approach. A purposive sampling method was employed to recruit emergency nurses who worked in public hospitals in Hong Kong. Semi-structured interviews were conducted to 24 emergency nurses. The data were interpreted using a thematic analysis strategy. Results: Five overarching themes emerged from the data: (1) the novelty of an emerging infectious disease, (2) the severity of an emerging infectious disease, (3) the proximity to an emerging infectious disease, (4) the complexity of an emerging infectious disease situation, and (5) the response levels towards an emerging infectious disease situation. Conclusion: It is anticipated that the information may help to predict the attitudes and behaviours of emergency nurses in future impending epidemic events, enhancing emergency nurses’ preparedness towards in such situations. Abbreviations: EID: Emerging infectious disease; ED: Emergency department; SARS: Severe acute respiratory syndrome; MERS: Middle East respiratory syndrome; WHO: World Health Organization; RN: Registered nurse; APN: Advanced practice nurse; NO: Nursing officer


COVID-19—White matter and globus pallidum lesions: Demyelination or small-vessel vasculitis?


title: “Quarantine during COVID-19 outbreak: changes in Diet and physical activity increase the risk of cardiovascular disease”

text: Abstract Aims CoV-19/SARS-CoV-2 is a highly pathogenic virus that is causing a global pandemic with a high number of deaths and infected people. To contain the diffusion of infection, several Governments have enforced restrictions on outdoor activities or even collective quarantine on the population. The present commentary briefly analyzes the effects of quarantine on lifestyle, including nutrition and physical activity and the impact of new technologies in dealing with this situation. Data Synthesis Quarantine is associated with stress and depression leading to unhealthy diet and reduced physical activity. A diet poor in fruit and vegetables is frequent during isolation, with a consequent low intake of antioxidants and vitamins. However, vitamins have recently been identified as a principal weapon in the fight against the Cov-19 virus. Some reports suggest that Vitamin D could exert a protective effect on such infection. During quarantine, strategies to further increase home-based physical activity and to encourage adherence to a healthy diet should be implemented. The WHO has just released guidance for people in self-quarantine, those without any symptoms or diagnosis of acute respiratory illness, which provides practical advice on how to stay active and reduce sedentary behaviour while at home. Conclusions Quarantine carries some long-term effects on cardiovascular disease, mainly related to unhealthy lifestyle and anxiety. Following quarantine, a global action supporting healthy Diet and physical activity is mandatory to encourage people to return to a good lifestyle routine.


title: Performance evaluation of ExiStation HBV diagnostic system for hepatitis B virus DNA quantitation

text: Abstract The performance of a recently developed real-time PCR system, the ExiStation HBV diagnostic system, for quantitation of hepatitis B virus (HBV) in human blood was evaluated. The detection limit, reproducibility, cross-reactivity, and interference were evaluated as measures of analytical performance. For the comparison study, 100 HBV-positive blood samples and 100 HBV-negative samples from Korean Blood Bank Serum were used, and the results of the ExiStation HBV system showed good correlation with those obtained using the Cobas TaqMan (r 2 =0.9931) and Abbott real-time PCR systems (r 2 =0.9894). The lower limit of detection was measured as 9.55IU/mL using WHO standards and the dynamic range was linear from 6.68 to 6.68×109 IU/mL using cloned plasmids. The within-run coefficient of variation (CV) was 9.4%, 2.1%, and 1.1%, and the total CV was 11.8%, 3.6%, and 1.7% at a concentration of 1.92log10 IU/mL, 3.88log10 IU/mL, and 6.84log10 IU/mL, respectively. No cross-reactivity or interference was detected. The ExiStation HBV diagnostic system showed satisfactory analytical sensitivity, excellent reproducibility, no cross-reactivity, no interference, and high agreement with the Cobas TaqMan and Abbott real-time PCR systems, and is therefore a useful tool for the detection and monitoring of HBV infection.