title: Asthma

text: Asthma is the most common inflammatory disease of the lungs. The prevalence of asthma is increasing in many parts of the world that have adopted aspects of the Western lifestyle, and the disease poses a substantial global health and economic burden. Asthma involves both the large-conducting and the small-conducting airways, and is characterized by a combination of inflammation and structural remodelling that might begin in utero. Disease progression occurs in the context of a developmental background in which the postnatal acquisition of asthma is strongly linked with allergic sensitization. Most asthma cases follow a variable course, involving viral-induced wheezing and allergen sensitization, that is associated with various underlying mechanisms (or endotypes) that can differ between individuals. Each set of endotypes, in turn, produces specific asthma characteristics that evolve across the lifecourse of the patient. Strong genetic and environmental drivers of asthma interconnect through novel epigenetic mechanisms that operate prenatally and throughout childhood. Asthma can spontaneously remit or begin de novo in adulthood, and the factors that lead to the emergence and regression of asthma, irrespective of age, are poorly understood. Nonetheless, there is mounting evidence that supports a primary role for structural changes in the airways with asthma acquisition, on which altered innate immune mechanisms and microbiota interactions are superimposed. On the basis of the identification of new causative pathways, the subphenotyping of asthma across the lifecourse of patients is paving the way for more-personalized and precise pathway-specific approaches for the prevention and treatment of asthma, creating the real possibility of total prevention and cure for this chronic inflammatory disease. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrdp.2015.25) contains supplementary material, which is available to authorized users.


title: Bicontinuous cubic phases in biological and artificial self-assembled systems

text: Nature has created innumerable life forms with miraculous hierarchical structures and morphologies that are optimized for different life events through evolution over billions of years. Bicontinuous cubic structures, which are often described by triply periodic minimal surfaces (TPMSs) and their constant mean curvature (CMC)/parallel surface companions, are of special interest to various research fields because of their complex form with unique physical functionalities. This has prompted the scientific community to fully understand the formation, structure, and properties of these materials. In this review, we summarize and discuss the formation mechanism and relationships of the relevant biological structures and the artificial self-assembly systems. These structures can be formed through biological processes with amazing regulation across a great length scales; nevertheless, artificial construction normally produces the structure corresponding to the molecular size and shape. Notably, the block copolymeric system is considered to be an applicable and attractive model system for the study of biological systems due to their versatile design and rich phase behavior. Some of the phenomena found in these two systems are compared and discussed, and this information may provide new ideas for a comprehensive understanding of the relationship between molecular shape and resulting interface curvature and the self-assembly process in living organisms. We argue that the co-polymeric system may serve as a model to understand these biological systems and could encourage additional studies of artificial self-assembly and the creation of new functional materials.


title: Making vaccines “on demand”: A potential solution for emerging pathogens and biodefense?

text: The integrated US Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) has made great strides in strategic preparedness and response capabilities. There have been numerous advances in planning, biothreat countermeasure development, licensure, manufacturing, stockpiling and deployment. Increased biodefense surveillance capability has dramatically improved, while new tools and increased awareness have fostered rapid identification of new potential public health pathogens. Unfortunately, structural delays in vaccine design, development, manufacture, clinical testing and licensure processes remain significant obstacles to an effective national biodefense rapid response capability. This is particularly true for the very real threat of “novel pathogens” such as the avian-origin influenzas H7N9 and H5N1, and new coronaviruses such as hCoV-EMC. Conventional approaches to vaccine development, production, clinical testing and licensure are incompatible with the prompt deployment needed for an effective public health response. An alternative approach, proposed here, is to apply computational vaccine design tools and rapid production technologies that now make it possible to engineer vaccines for novel emerging pathogen and WMD biowarfare agent countermeasures in record time. These new tools have the potential to significantly reduce the time needed to design string-of-epitope vaccines for previously unknown pathogens. The design process—from genome to gene sequence, ready to insert in a DNA plasmid—can now be accomplished in less than 24 h. While these vaccines are by no means “standard,” the need for innovation in the vaccine design and production process is great. Should such vaccines be developed, their 60-d start-to-finish timeline would represent a 2-fold faster response than the current standard.


title: The closterovirus-derived gene expression and RNA interference vectors as tools for research and plant biotechnology

text: Important progress in understanding replication, interactions with host plants, and evolution of closteroviruses enabled engineering of several vectors for gene expression and virus-induced gene silencing. Due to the broad host range of closteroviruses, these vectors expanded vector applicability to include important woody plants such as citrus and grapevine. Furthermore, large closterovirus genomes offer genetic capacity and stability unrivaled by other plant viral vectors. These features provided immense opportunities for using closterovirus vectors for the functional genomics studies and pathogen control in economically valuable crops. This review briefly summarizes advances in closterovirus research during the last decade, explores the relationships between virus biology and vector design, and outlines the most promising directions for future application of closterovirus vectors.


title: Community-acquired pneumonia in children

text: Community acquired pneumonia (CAP) is common in childhood. Viruses account for most cases of CAP during the first two years of life. After this period, bacteria such as Streptococcus pneumoniae, Mycoplasma pneumoniae and Chlamydia pneumoniae become more frequent. CAP symptoms are nonspecific in younger infants, but cough and tachypnea are usually present in older children. Chest x-ray is useful for confirming the diagnosis. Most children can be managed empirically with oral antibiotics as outpatients without specific laboratory investigations. Those with severe infections or with persistent or worsening symptoms need more intensive investigations and may need admission to hospital. The choice and dosage of antibiotics should be based on the age of the patient, severity of the pneumonia and knowledge of local antimicrobial resistance patterns. The Canadian Paediatric Society recommends the use of the heptavalent conjugate pneumococcal vaccine, which is efficacious in reducing chest x-ray positive pneumonia by up to 20%.


title: Incidence and Determinants of QT Interval Prolongation in COVID‐19 Patients Treated with Hydroxychloroquine and Azithromycin

text: Combined use of hydroxychloroquine and azithromycin was globally adopted, in part due to paucity and high cost of alternative therapies. However the utility of these medications has been questioned; and thus safety becomes a major concern given clinical equipoise regarding efficacy. This article is protected by copyright. All rights reserved.


title: Review of the Lithuanian Alcohol Control Legislation in 1990–2020

text: Since the early 1990s, Lithuania has experienced an increasing level of alcohol consumption and a heavy burden of alcohol-related harm, which is associated with the development of alcohol policies. The aim of this analysis was to provide a chronology of change of Lithuanian alcohol control legislation and to present several other detailed examples of the political processes. The data were collected using document reviews. During the last three decades, the Lithuanian alcohol control policies have undergone several cycles of stricter control and liberalizations. Some of the limitations of the study are the exceptional focus on the public health perspective and the inclusion of policies targeting the population as a whole. The strength of the study is in providing a detailed background for future policy effectiveness studies. Some of the recent periods when a series of ‘best buy’ interventions were implemented during a short period are of particular importance, constituting a natural experiment, whose effects need to be studied in more detail in the future.


title: Detection and Characterization of Distinct Alphacoronaviruses in Five Different Bat Species in Denmark

text: Bat populations harbour a multitude of viruses; some of these are pathogenic or potentially pathogenic in other animals or humans. Therefore, it is important to monitor the populations and characterize these viruses. In this study, the presence of coronaviruses (CoVs) in different species of Danish bats was investigated using active surveillance at different geographical locations in Denmark. Faecal samples were screened for the presence of CoVs using pan-CoV real-time RT-PCR assays. The amplicons, obtained from five different species of bats, were sequenced. Phylogenetic analysis revealed a species-specific clustering with the samples from Myotis daubentonii, showing a close resemblance to coronavirus sequences obtained from the same species of bat in Germany and the United Kingdom. Our results show, for the first time, that multiple, distinct alphacoronaviruses are present in the Danish bat populations.


title: From White Count to White Out

text: We present a 6-month-old boy with failure to thrive who was referred to the emergency department by his primary care doctor for leukocytosis and was found to be hypoxic with diffuse infiltrates on chest radiograph. Our patient was admitted and eventually diagnosed with Pneumocystis jirovecii pneumonia secondary to hyper immunoglobulin M syndrome. Even though P jirovecii pneumonia is an uncommon cause of hypoxia in infants, this case illustrates the need for pediatric emergency physicians to be cognizant of this rare but life threatening cause of hypoxia.


title: Preparation of novel (Z)-4-ylidenebenzo[b]furo[3,2-d][1,3]oxazines and their biological activity()

text: A reaction of 2-acetyl-3-acylaminobenzo[b]furans (9d–o) with Vilsmeier (VM) reagent afforded a mixture of (E)- and (Z)-{(E)-2-aralkenylbenzo[b]furo[3,2-d][1,3]oxazin-4-ylidene}acetaldehydes (5) with a characteristic exo-formylmethylene group on the oxazine ring. The Z-isomer was more stable than the E-isomer. The Z-isomers ((Z)-5) were reacted with phosphonate reagents under two different conditions to obtain various butadiene derivatives (12) containing benzo[b]furo[3,2-d][1,3]oxazine skeleton. Typical compounds (5 and 12) were evaluated for their anti-osteoclastic bone resorption activity, antagonistic activity for the cysLT1 receptor and growth inhibitory activity for MIA PaCa-2 and MCF-7. Compounds 12f and 12j showed potent anti-osteoclastic bone resorption activity comparable to E(2) (17β-estradiol).


title: PI3K-Akt-mTOR axis sustains rotavirus infection via the 4E-BP1 mediated autophagy pathway and represents an antiviral target

text: Rotavirus infection is a major cause of severe dehydrating diarrhea in infants younger than 5 y old and in particular cases of immunocompromised patients irrespective to the age of the patients. Although vaccines have been developed, antiviral therapy is an important complement that cannot be substituted. Because of the lack of specific approved treatment, it is urgent to facilitate the cascade of further understanding of the infection biology, identification of druggable targets and the final development of effective antiviral therapies. PI3K-Akt-mTOR signaling pathway plays a vital role in regulating the infection course of many viruses. In this study, we have dissected the effects of PI3K-Akt-mTOR signaling pathway on rotavirus infection using both conventional cell culture models and a 3D model of human primary intestinal organoids. We found that PI3K-Akt-mTOR signaling is essential in sustaining rotavirus infection. Thus, blocking the key elements of this pathway, including PI3K, mTOR and 4E-BP1, has resulted in potent anti-rotavirus activity. Importantly, a clinically used mTOR inhibitor, rapamycin, potently inhibited both experimental and patient-derived rotavirus strains. This effect involves 4E-BP1 mediated induction of autophagy, which in turn exerts anti-rotavirus effects. These results revealed new insights on rotavirus-host interactions and provided new avenues for antiviral drug development.


title: Impact of COVID-19 on the Practice of Clinical Radiology

text: We examine the impact of COVID-19 on the future of Radiology in the following domains: employment/compensation/practice; location and hours of work; workplace environment and safety; activities beyond the “usual scope” of practice; and CME/meetings/professional organizations.


title: COVID-19: Don't Neglect the Gastrointestinal Tract!

text: n/a.


title: Chapter 5 Common Myths and Legends of Rabies

text: Abstract Humankind has somewhat of a dark, yet almost fascinating, supernatural relationship with rabies. Even after Pasteur's rabies vaccine discovery, globally people continue to be stricken with it today. History has carried along the myths and legends that surround this diabolical virus. Some still believe that rabies treatment requires 20 or more shots to the stomach by some monstrously long needle. However, today's treatment regimen is typically only four vaccinations (five for immunocompromised) in the arm, plus human rabies immune globulin. This chapter explores the misunderstood concepts of rabies prevalence, signs and symptoms, exposures, and treatment protocols.


title: Neuroimaging findings in COVID-19 and other coronavirus infections: a systematic review in 116 patients

text: Abstract Various neurologic syndromes have been described in patients with COVID-19 and other coronavirus infections. In this paper, we systematically reviewed the available imaging findings of patients diagnosed with neurological symptoms associated with coronavirus infections. Diverse radiologic results in the context of different neurologic presentations have been demonstrated using CT and MRI. While many patients have normal imaging evaluations, some patients present with intra-axial and extra-axial abnormalities. Stroke (both ischemic and hemorrhagic), encephalomyelitis, meningitis, demyelinating disorders such as acute disseminated encephalomyelitis (ADEM), and encephalopathy have been reported. Familiarity with these radiologic patterns will guide radiologists and referring clinicians to consider coronavirus infections in patients with worsening or progressive neurologic findings, particularly during the current COVID-19 pandemic. As data on this topic is very limited, further research and investigation are required.


title: Role of fomites in SARS transmission during the largest hospital outbreak in Hong Kong

text: The epidemic of severe acute respiratory syndrome (SARS) had a significant effect on global society in the early 2000s and the potential of its resurgence exists. Studies on the modes of transmission of SARS are limited though a number of outbreak studies have revealed the possible airborne route. To develop more specific and effective control strategies, we conducted a detailed mechanism-based investigation that explored the role of fomite transmission in the well-known Ward 8A outbreak. We considered three hypothetical transmission routes, i.e., the long-range airborne, fomite and combined routes, in 1,744 scenarios with combinations of some important parameters. A multi-agent model was used to predict the infection risk distributions of the three hypothetical routes. Model selection was carried out for different scenarios to compare the distributions of infection risk with that of the reported attack rates and select the hypotheses with the best fitness. Our results reveal that under the assumed conditions, the SARS coronavirus was most possible to have spread via the combined long-range airborne and fomite routes, and that the fomite route played a non-negligible role in the transmission.


title: Elective tracheostomy during COVID-19 outbreak: to whom, when, how? Early experience from Venice, Italy

text: PURPOSE: The need for prolonged invasive mechanical ventilation in COVID-19 patients is placing the otorhinolaryngologist in front of an increasing request for tracheostomy. Nowadays, there is uncertainty regarding the timing of tracheostomy, the prognosis of these patients and the safety of healthcare workers. The aim of this study is to evaluate the efficacy and safety of tracheostomy placement in patients with COVID-19. METHODS: A retrospective cohort study on 23 COVID 19 patients, to analyse the timing of tracheostomy, the risk factors associated with in-hospital death and the infection of the involved health care workers. Early tracheostomy was defined as ≤ 10 days and late ones > 10 days. RESULTS: The mortality rate of COVID-19 patients admitted to ICU that underwent tracheostomy was 18%. The overall mortality of patients admitted to ICU was 53%. The univariate analysis revealed that early tracheostomy, SOFA score > 6, and D-dimer level > 4 were significantly associated with a greater risk of death. At the multivariate analysis SOFA score > 6 and D-dimer level > 4 resulted as significant factors for a higher risk of death. No health care workers associated with tracheostomy are confirmed to be infected by SARS-CoV2. CONCLUSION: We suggest to wait at least 14 days to perform tracheostomy. In patients with SOFA score > 6 and D dimer > 4, tracheostomy should not be performed or should be postponed. Optimized procedures and enhanced personal protective equipment can make the tracheostomy safe and beneficial in COVID-19 patients.


title: Decontamination of rooms, medical equipment and ambulances using an aerosol of hydrogen peroxide disinfectant

text: Summary A programmable device (Sterinis, Gloster Sante Europe) providing a dry fume of 5% hydrogen peroxide (H2O2) disinfectant was tested for decontamination of rooms, ambulances and different types of medical equipment. Pre-set concentrations were used according to the volumes of the rooms and garages. Three cycles were performed with increasing contact times. Repetitive experiments were performed using Bacillus atrophaeus (formerly Bacillus subtilis) Raven 1162282 spores to control the effect of decontamination; after a sampling plan, spore strips were placed in various positions in rooms, ambulances, and inside and outside the items of medical equipment. Decontamination was effective in 87% of 146 spore tests in closed test rooms and in 100% of 48 tests in a surgical department when using three cycles. One or two cycles had no effect. The sporicidal effect on internal parts of the medical equipment was only 62.3% (220 tests). When the devices were run and ventilated during decontamination, 100% (57/57) of spore strips placed inside were decontaminated. In the ambulances, the penetration of H2O2 into equipment, devices, glove boxes, under mattresses, and the drivers' cabins was 100% (60/60 tests) when using three cycles, but was less effective when using one or two cycles. In conclusion, an H2O2 dry fumigation system, run in three cycles, seemed to have a good sporicidal effect when used in rooms, ambulances, and external and internal parts of ventilated equipment. Further studies need to be performed concerning concentration, contact time and the number of cycles of H2O2. This is especially important for inner parts of medical equipment that cannot be ventilated during the decontamination process.


A Comment on “Quaternary Prevention in Public Health” by Dr. Jong-Myon Bae


title: Pericollapse Stage of Osteonecrosis of the Femoral Head: A Last Chance for Joint Preservation

text: OBJECTIVE: To propose a new definition of the pericollapse stage of osteonecrosis of the femoral head (ONFH) and review its significance in disease diagnosis and treatment selection. DATA SOURCES: A search for eligible studies was conducted in three electronic databases including PubMed, Cochrane Library, and Embase up to August 10, 2018, using the following keywords: “osteonecrosis”, “prognosis”, and “treatment”. STUDY SELECTION: Investigations appraising the clinical signs, symptoms, and imaging manifestations in different stages of ONFH were included. Articles evaluating the prognosis of various joint-preserving procedures were also reviewed. RESULTS: The pericollapse stage refers to a continuous period in the development of ONFH from the occurrence of subchondral fracture to early collapse (<2 mm), possessing specific imaging features that mainly consist of bone marrow edema and joint effusion on magnetic resonance imaging (MRI), crescent signs on X-ray films, and clinical manifestations such as the sudden worsening of hip pain. Accumulating evidence has indicated that these findings may be secondary to the changes after subchondral fractures. Of note, computed tomography provides more information for identifying possible subchondral fractures than does MRI and serves as the most sensitive tool for grading the pericollapse lesion stage. The pericollapse stage may indicate a high possibility of progressive disease but also demonstrates satisfactory long- and medium-term outcomes for joint-preserving techniques. In fact, if the articular surface subsides more than 2 mm, total hip arthroplasty is preferable. CONCLUSIONS: The pericollapse stage with distinct clinical and imaging characteristics provides a last good opportunity for the use of joint-preserving techniques. It is necessary to separate the pericollapse stage as an independent state in evaluating the natural progression of ONFH and selecting an appropriate treatment regimen.


The Use of Respirators to Reduce Inhalation of Airborne Biological Agents


Positive strand RNA virus replication: It depends on the ends


title: Role and mechanism of angiotensin-converting enzyme 2 in acute lung injury in coronavirus disease 2019

text: Coronavirus disease 2019 is a major threat to public health globally. Though its pathogenesis has not been fully elucidated, angiotensin-converting enzyme 2 (ACE2) has been recently identified as a receptor for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the cell. Here, we aimed to clarify the potential role of ACE2 in SARS-CoV-2-induced acute lung injury and its underlying mechanism. As a receptor for coronavirus, ACE2 mediates the entry of SARS-CoV-2 into cells in a similar way as for severe acute respiratory syndrome coronavirus (SARS-CoV). The high binding affinity of SARS-CoV-2 to ACE2 correlates with its efficient spread among humans. On the other hand, ACE2 negatively regulates the renin-angiotensin-aldosterone system (RAAS) primarily by converting angiotensin II to angiotensin 1–7, which exerts a beneficial effect on coronavirus-induced acute lung injury. Human recombinant ACE2 has been considered as a potential therapy for SARS-CoV-2 by blocking virus entry and redressing the imbalance of RAAS in SARS-CoV-2 infection. The level of ACE2 expression can be upregulated by treatment with an ACE inhibitor (ACEI) or angiotensin Ⅱ type 1 receptor blocker (ARB). To date, no evidence shows that ACEIs or ARBs increase the susceptibility and mortality of patients infected with SARS-CoV-2, and hence, it is not advisable to discontinue such drugs in patients with cardiovascular disease.


title: HCMV glycoprotein B subunit vaccine efficacy was mediated by non-neutralizing antibody effector functions

text: Human cytomegalovirus (HCMV) is the most common congenital infection worldwide, frequently causing hearing loss and brain damage in afflicted infants. A vaccine to prevent maternal acquisition of HCMV during pregnancy is necessary to reduce the incidence of infant disease. The glycoprotein B (gB) + MF59 adjuvant subunit vaccine platform is the most successful HCMV vaccine tested to-date, demonstrating approximately 50% efficacy in preventing HCMV acquisition in phase II trials. However, the mechanism of vaccine protection remains unknown. Plasma from 33 gB/MF59 vaccinees at peak immunogenicity was tested for gB epitope specificity as well as neutralizing and non-neutralizing anti-HCMV effector functions, and compared to an HCMV-seropositive cohort. gB/MF59 vaccination elicited IgG responses with gB-binding magnitude and avidity comparable to natural infection. Additionally, IgG subclass distribution was similar with predominant IgG1 and IgG3 responses induced by gB vaccination and HCMV infection. However, vaccine-elicited antibodies exhibited limited neutralization of the autologous virus, negligible neutralization of multiple heterologous strains, and limited binding responses against gB structural motifs targeted by neutralizing antibodies including AD-1, AD-2, and Domain I. Interestingly, vaccinees had high-magnitude IgG responses against AD-3 linear epitopes, demonstrating immunodominance against this non-neutralizing, cytosolic region. Finally, vaccine-elicited IgG robustly bound trimeric, membrane-associated gB on the surface of transfected or HCMV-infected cells and mediated virion phagocytosis, though were poor mediators of NK cell activation. Altogether, these data suggest that non-neutralizing antibody functions, including virion phagocytosis, likely played a role in the observed 50% vaccine-mediated protection against HCMV acquisition. The CDC estimates that every hour, a child is born in the United States with permanent neurologic disability resulting from human cytomegalovirus (HCMV) infection – more than is caused by Down syndrome, fetal alcohol syndrome, and neural tube defects combined. A maternal vaccine to block transmission of HCMV to the developing fetus is a necessary intervention to prevent these adverse outcomes. The gB/MF59 vaccine is the most successful tested clinically to-date, achieving 50% reduction in HCMV acquisition. This manuscript establishes the function and epitope specificity of the humoral response stimulated by this vaccine that may explain the partial vaccine efficacy. Understanding the mechanism of gB/MF59-elicited protective immune responses will guide rational design and evaluation of the next generation of HCMV vaccines.


title: Challenges in maintaining treatment services for people who use drugs during the COVID-19 pandemic

text: The impact of COVID-19 across health services, including treatment services for people who use drugs, is emerging but likely to have a high impact. Treatment services for people who use drugs provide essential treatment services including opiate agonist treatment and needle syringe programmes alongside other important treatment programmes across all substance types including withdrawal and counselling services. Drug and alcohol hospital consultation-liaison clinicians support emergency departments and other services provided in hospital settings in efficiently managing patients who use drugs and present with other health problems. COVID-19 will impact on staff availability for work due to illness. Patients may require home isolation and quarantine periods. Ensuring ongoing supply of opiate treatment during these periods will require significant changes to how treatment is provided. The use of monthly depot buprenorphine as well as moving from a framework of supervised dosing will be required for patients on sublingual buprenorphine and methadone. Ensuring ready access to take-home naloxone for patients is crucial to reduce overdose risks. Delivery of methadone and buprenorphine to the homes of people with confirmed COVID-19 infections is likely to need to occur to support home isolation. People who use drugs are likely to be more vulnerable during the COVID-19 epidemic, due to poorer health literacy and stigma and discrimination towards this group. People who use drugs may prioritise drug use above other health concerns. Adequate supply of clean injecting equipment is important to prevent outbreaks of blood-borne viruses. Opiate users may misinterpret SARS-CoV2 symptoms as opiate withdrawal and manage this by using opioids. Ensuring people who use drugs have access to drug treatment as well as access to screening and testing for SARS-CoV2 where this is indicated is important.


title: Nonstructural protein 9 residues 586 and 592 are critical sites in determining the replication efficiency and fatal virulence of the Chinese highly pathogenic porcine reproductive and respiratory syndrome virus

text: Abstract The highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) has caused huge economic losses to the swine industry in China. Understanding the molecular basis in relation to the virulence of HP-PRRSV is essential for effectively controlling clinical infection and disease. In the current study, we constructed and rescued a serial of mutant viruses in nsp9 and nsp10 based on the differential amino acid sites between HP-PRRSV JXwn06 and LP-PRRSV HB-1/3.9. The replication efficiency in pulmonary alveolar macrophages (PAMs) and the pathogenicity of the mutant viruses for piglets were analyzed. Our results showed that the mutation of Thr to Ala in 586 and Ser to Thr in 592 of nsp9 decreased the replication efficiency of HP-PRRSV in PAMs, and could attenuate its virulence for piglets, suggesting that the residues 586 and 592 of nsp9 are critical sites natively in determining the fatal virulence of the Chinese HP-PRRSV for piglets.


title: Application of a Real-Time Polymerase Chain Reaction with Internal Positive Control for Detection and Quantification of Enterovirus in Cerebrospinal Fluid

text: A quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) method based on TaqMan technology was developed to determine the presence and amount of enterovirus RNA. In order to prevent false-negative results, a one-step multiplex RT-PCR was optimized. It contains two dual-labelled fluorogenic probes to quantify the 5′ noncoding region of enterovirus and detect an internal positive control. In the present study, 104 cerebrospinal fluid samples collected during an outbreak of enteroviral meningitis were analyzed using this method. Amplification of the internal positive control was effective in all but two specimens, confirming the absence of PCR inhibitors and allowing the results of amplification to be validated. The sensitivity of the RT-PCR was 96.8%, while that of cell culture was 34.9%. Genomic viral loads found ranged between 3.3 and 5.9 log(10) copies per milliliter of cerebrospinal fluid (mean, 4.8 log(10) copies/ml). This fluorogenic enterovirus RT-PCR allows large numbers of samples to be screened rapidly. Moreover, its sensitivity and reproducibility make it highly reliable. With these characteristics, the enterovirus RT-PCR can be a useful tool that may offer considerable benefit in the clinical management of patients with enteroviral infections.


title: Isolation is not the answer

text: International scientific collaboration is the best defence against bioterror.


title: Effect of preweaning feeding of pasteurized and nonpasteurized milk on postweaning weight gain of heifer calves on a Californian dairy

text: Abstract The effect of preweaning feeding of pasteurized colostrum and pasteurized waste milk on postweaning performance of dairy heifers on a dairy in the Central Valley of California was investigated as an extension of a clinical trial examining the effect of preweaning growth and morbidity on performance at weaning. Of the 150 heifer calves originally enrolled in the field trial, 115 calves (59 treatment, 56 controls) were followed to about 6 months of age, during which time their weights were measured. After weights were adjusted for several potential risk factors and effect modifiers, calves fed pasteurized colostrum and pasteurized waste milk were 3.7 kg heavier at 180 days of age than those fed nonpasteurized colostrum and nonpasteurized milk.


title: Personalized recovery of severe COVID19: Rehabilitation from the perspective of patient needs

text: After long term hospitalization or ICU treatment, COVID‐19 patients are severe functionally impaired. They experience not only physical weakness but may also suffer from problems on the pulmonary, physical, psychosocial and cognitive domain. These domains interact and the impact on participation varies between patients. Therefore aftercare should be costumized to the patients individual needs. In this article we present a patient centered model to tailor treatment in the view of the Dutch health care system. This model can be helpful to determine the appropriate treatment for each patient at the right time in the right setting


title: Bats Without Borders: Long-Distance Movements and Implications for Disease Risk Management

text: Fruit bats of the genus Pteropus (commonly known as flying-foxes) are the natural hosts of several recently emerged zoonotic viruses of animal and human health significance in Australia and Asia, including Hendra and Nipah viruses. Satellite telemetry was used on nine flying-foxes of three species (Pteropus alecto n = 5, P. vampyrus n = 2, and P. neohibernicus n = 2) to determine the scale and pattern of their long-distance movements and their potential to transfer these viruses between countries in the region. The animals were captured and released from six different locations in Australia, Papua New Guinea, Indonesia, and Timor-Leste. Their movements were recorded for a median of 120 (range, 47–342) days with a median total distance travelled of 393 (range, 76–3011) km per individual. Pteropus alecto individuals were observed to move between Australia and Papua New Guinea (Western Province) on four occasions, between Papua New Guinea (Western Province) and Indonesia (Papua) on ten occasions, and to traverse Torres Strait on two occasions. Pteropus vampyrus was observed to move between Timor-Leste and Indonesia (West Timor) on one occasion. These findings expand upon the current literature on the potential for transfer of zoonotic viruses by flying-foxes between countries and have implications for disease risk management and for the conservation management of flying-fox populations in Australia, New Guinea, and the Lesser Sunda Islands.


title: Quantification and determinants of the amount of respiratory syncytial virus (RSV) shed using real time PCR data from a longitudinal household study

text: Background: A better understanding of respiratory syncytial virus (RSV) epidemiology requires realistic estimates of RSV shedding patterns, quantities shed, and identification of the related underlying factors. Methods: RSV infection data arise from a cohort study of 47 households with 493 occupants, in coastal Kenya, during the 2009/2010 RSV season. Nasopharyngeal swabs were taken every 3 to 4 days and screened for RSV using a real time polymerase chain reaction (PCR) assay. The amount of virus shed was quantified by calculating the ‘area under the curve’ using the trapezoidal rule applied to rescaled PCR cycle threshold output. Multivariable linear regression was used to identify correlates of amount of virus shed. Results: The median quantity of virus shed per infection episode was 29.4 (95% CI: 15.2, 54.2) log (10 )ribonucleic acid (RNA) copies * days. Young age (<1 year), presence of upper respiratory symptoms, intra-household acquisition of infection, an individual’s first infection episode in the RSV season, and having a co-infection of RSV group A and B were associated with increased amount of virus shed. Conclusions: The findings provide insight into which groups of individuals have higher potential for transmission, information which may be useful in designing RSV prevention strategies.


title: Plasmacytoid dendritic cells: one-trick ponies or workhorses of the immune system?

text: Plasmacytoid dendritic cells (pDCs) were first described as interferon-producing cells and, for many years, their overlapping characteristics with both lymphocytes and classical dendritic cells (cDCs) created confusion over their exact ontogeny. In this Viewpoint article, Nature Reviews Immunology asks five leaders in the field to discuss their thoughts on the development and functions of pDCs — do these cells serve mainly as a major source of type I interferons or do they also make other important contributions to immune responses?


Prevention of fogging of protective eyewear for medical staff during the COVID-19 pandemic


title: No observed effect of homologous recombination on influenza C virus evolution

text: The occurrence of homologous recombination in influenza viruses has been under some debate recently. To determine the extent of homologous recombination in influenza C virus, recombination analyses of all available gene sequences of influenza C virus were carried out. No recombination signal was found. With the previous evidence in influenza A and B viruses, it seems that homologous recombination has minimal or no effect on influenza virus evolution.


title: One Health: Past Successes and Future Challenges in Three African Contexts

text: BACKGROUND: The recent emergence of zoonotic diseases such as Highly Pathogenic Avian Influenza (HPAI) and Severe Acute Respiratory Syndrome (SARS) have contributed to dominant Global Health narratives around health securitisation and pandemic preparedness, calling for greater co-operation between the health, veterinary and environmental sectors in the ever-evolving One Health movement. A decade later, One Health advocates face increasing pressure to translate the approach from theory into action. METHODOLOGY/PRINCIPAL FINDINGS: A qualitative case study methodology was used to examine the emerging relationships between international One Health dialogue and its practical implementation in the African health policy context. A series of Key Informant Interviews (n = 32) with policy makers, government officials and academics in Nigeria, Tanzania and Uganda are presented as three separate case studies. Each case examines a significant aspect of One Health operationalisation, framed around the control of both emerging and Neglected Zoonotic Diseases including HPAI, Human African Trypanosomiasis and rabies. The research found that while there is general enthusiasm and a strong affirmative argument for adoption of One Health approaches in Africa, identifying alternative contexts away from a narrow focus on pandemics will help broaden its appeal, particularly for national or regionally significant endemic and neglected diseases not usually addressed under a “global” remit. CONCLUSIONS/SIGNIFICANCE: There is no ‘one size fits all’ approach to achieving the intersectoral collaboration, significant resource mobilisation and political co-operation required to realise a One Health approach. Individual country requirements cannot be underestimated, dismissed or prescribed in a top down manner. This article contributes to the growing discussion regarding not whether One Health should be operationalised, but how this may be achieved.


title: Make Data Sharing Routine to Prepare for Public Health Emergencies

text: Jean-Paul Chretien and colleagues argue that recent Ebola and Zika virus outbreaks highlight the importance of data sharing in scientific research.


Coronavirus Disease 2019: Harnessing Healthy Fear via Knowledge, Attitudes, and Behavior


title: Infection prevention and chronic disease management in cystic fibrosis and noncystic fibrosis bronchiectasis

text: Bronchiectasis is a chronic lung disease (CLD) characterized by irreversible bronchial dilatation noted on computed tomography associated with chronic cough, ongoing viscid sputum production, and recurrent pulmonary infections. Patients with bronchiectasis can be classified into two groups: those with cystic fibrosis and those without cystic fibrosis. Individuals with either cystic fibrosis related bronchiectasis (CFRB) or noncystic fibrosis related bronchiectasis (NCFRB) experience continuous airway inflammation and suffer airway architectural changes that foster the acquisition of a unique polymicrobial community. The presence of microorganisms increases airway inflammation, triggers pulmonary exacerbations (PEx), reduces quality of life (QOL), and, in some cases, is an independent risk factor for increased mortality. As there is no cure for either condition, prevention and control of infection is paramount. Such an undertaking incorporates patient/family and healthcare team education, immunoprophylaxis, microorganism source control, antimicrobial chemoprophylaxis, organism eradication, daily pulmonary disease management, and, in some cases, thoracic surgery. This review is a summary of recommendations aimed to thwart patient acquisition of pathologic organisms, and those therapies known to mitigate the effects of chronic airway infection. A thorough discussion of airway clearance techniques and treatment of or screening for nontuberculous mycobacteria (NTM) is beyond the scope of this discussion.


title: The 2019 coronavirus (SARS-CoV-2) surface protein (Spike) S1 Receptor Binding Domain undergoes conformational change upon heparin binding

text: Many pathogens take advantage of the dependence of the host on the interaction of hundreds of extracellular proteins with the glycosaminoglycans heparan sulfate to regulate homeostasis and use heparan sulfate as a means to adhere and gain access to cells. Moreover, mucosal epithelia such as that of the respiratory tract are protected by a layer of mucin polysaccharides, which are usually sulfated. Consequently, the polydisperse, natural products of heparan sulfate and the allied polysaccharide, heparin have been found to be involved and prevent infection by a range of viruses including S-associated coronavirus strain HSR1. Here we use surface plasmon resonance and circular dichroism to measure the interaction between the SARS-CoV-2 Spike S1 protein receptor binding domain (SARS-CoV-2 S1 RBD) and heparin. The data demonstrate an interaction between the recombinant surface receptor binding domain and the polysaccharide. This has implications for the rapid development of a first-line therapeutic by repurposing heparin and for next-generation, tailor-made, GAG-based antivirals.


title: The S2 Subunit of Infectious Bronchitis Virus Beaudette Is a Determinant of Cellular Tropism

text: The spike (S) glycoprotein of the avian gammacoronavirus infectious bronchitis virus (IBV) is comprised of two subunits (S1 and S2), has a role in virulence in vivo, and is responsible for cellular tropism in vitro. We have previously demonstrated that replacement of the S glycoprotein ectodomain from the avirulent Beaudette strain of IBV with the corresponding region from the virulent M41-CK strain resulted in a recombinant virus, BeauR-M41(S), with the in vitro cell tropism of M41-CK. The IBV Beaudette strain is able to replicate in both primary chick kidney cells and Vero cells, whereas the IBV M41-CK strain replicates in primary cells only. In order to investigate the region of the IBV S responsible for growth in Vero cells, we generated a series of recombinant IBVs expressing chimeric S glycoproteins, consisting of regions from the Beaudette and M41-CK S gene sequences, within the genomic background of Beaudette. The S2, but not the S1, subunit of the Beaudette S was found to confer the ability to grow in Vero cells. Various combinations of Beaudette-specific amino acids were introduced into the S2 subunit of M41 to determine the minimum requirement to confer tropism for growth in Vero cells. The ability of IBV to grow and produce infectious progeny virus in Vero cells was subsequently narrowed down to just 3 amino acids surrounding the S2′ cleavage site. Conversely, swapping of the 3 Beaudette-associated amino acids with the corresponding ones from M41 was sufficient to abolish Beaudette growth in Vero cells. IMPORTANCE Infectious bronchitis remains a major problem in the global poultry industry, despite the existence of many different vaccines. IBV vaccines, both live attenuated and inactivated, are currently grown on embryonated hen's eggs, a cumbersome and expensive process due to the fact that most IBV strains do not grow in cultured cells. The reverse genetics system for IBV creates the opportunity for generating rationally designed and more effective vaccines. The observation that IBV Beaudette has the additional tropism for growth on Vero cells also invokes the possibility of generating IBV vaccines produced from cultured cells rather than by the use of embryonated eggs. The regions of the IBV Beaudette S glycoprotein involved in the determination of extended cellular tropism were identified in this study. This information will enable the rational design of a future generation of IBV vaccines that may be grown on Vero cells.


title: Changing risk awareness and personal protection measures for low to high pathogenic avian influenza in live-poultry markets in Taiwan, 2007 to 2012

text: BACKGROUND: Outbreaks of low and high pathogenic avian influenza (LPAI, HPAI) H5N2 in chickens have occurred in Taiwan since 2003 and 2012, respectively. Fully understanding the different awareness, attitudes and protective behaviors adopted by workers in live-poultry markets (LPMWs) and local community residents (CRs) to face the challenges of LPAI and HPAI is very important to minimize viral adaptations to human populations. METHODS: A structural questionnaire containing information on respondents’ occupation, personal risk awareness, attitudes toward different policies, and preventative measures was administered. The two-stage survey (before and after HPAI H5N2 outbreaks) was conducted from 2007 to 2012, including: (1) 430 LPMWs and 418 CRs at LPMs from different geographical areas of Taiwan after the government announced outbreaks of LPAI H5N2 during 2007–2009, and (2) 73 LPMWs and 152 CRs at two LPMs in central Taiwan after the HPAI H5N2 outbreaks in 2012. The chi-squared test and logistic regression were applied for univariate and multivariate analyses, respectively. RESULTS: Before HPAI-H5N2 outbreaks, higher educated respondents demonstrated greater risk awareness and concerns regarding AI. However, LPM-workers protected themselves less from AI viruses (AIVs) and had lower acceptance of human or avian influenza vaccines. Most importantly, the participants who opposed (versus agreed with) the policy on banning live-poultry slaughtering at LPMs reported lower awareness of government prevention and control policies [Odds Ratio (OR): 0.76, 95 % Confidence Interval (CI): 0.56–1.01] or practiced preventive measures (OR: 0.42, 95 % CI: 0.25–0.70). After HPAI-H5N2 outbreaks, the risk awareness about AI in central Taiwan significantly increased [LPAI to HPAI LPMWs: 34.6 to 65.6 %, p < 0.05; CRs: 44.0 to 76.5 %, p < 0.05] and LPMWs’ belief in the effectiveness of vaccination to prevent human or avian influenza virus infection strikingly decreased (92.3 to 68.5 %, p < 0.05). CONCLUSIONS: Risk awareness depends on high or low pathogenicity of AIVs, working in LPMs, levels of education, age, and proximity to the sites of severe AI outbreaks. Regardless of novel LPAI or HPAI virus reassortants that pose public health risks, prompt and clear risk communication focusing on both correct information about AIVs and the most appropriate preventive measures are important for effective prevention of human infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-0987-8) contains supplementary material, which is available to authorized users.


title: Immunogenicity of a polyvalent HIV-1 candidate vaccine based on fourteen wild type gp120 proteins in golden hamsters

text: BACKGROUND: One of the major obstacles in the design of an effective vaccine against HIV-1 is the hypervariability of the HIV-1 envelope glycoprotein. Most HIV-1 vaccine candidates have utilized envelope glycoprotein from a single virus isolate, but to date, none of them elicited broadly reactive humoral immunity. Herein, we hypothesised that a cocktail of HIV-1 gp120 proteins containing multiple epitopes may increase the breadth of immune responses against HIV-1. We compared and evaluated the immunogenicity of HIV-1 vaccines containing either gp120 protein alone or in combinations of four or fourteen gp120s from different primary HIV-1 isolates in immunized hamsters. RESULTS: We amplified and characterized 14 different gp120s from primary subtype B isolates with both syncytium and non-syncytium inducing properties, and expressed the proteins in Chinese Hamster Ovary (CHO) cell lines. Purified proteins were used either alone or in combinations of four or fourteen different gp120s to vaccinate golden hamsters. The polyvalent vaccine showed higher antibody titers to HIV-1 subtype B isolates MN and SF162 compared to the groups that received one or four gp120 proteins. However, the polyvalent vaccine was not able to show higher neutralizing antibody responses against HIV-1 primary isolates. Interestingly, the polyvalent vaccine group had the highest proliferative immune responses and showed a substantial proportion of cross-subtype CD4 reactivity to HIV-1 subtypes B, C, and A/E CONCLUSION: Although the polyvalent approach achieved only a modest increase in the breadth of humoral and cellular immunity, the qualitative change in the vaccine (14 vs. 1 gp120) resulted in a quantitative improvement in vaccine-induced immunity.


title: Stability issues of RT‐PCR testing of SARS‐CoV‐2 for hospitalized patients clinically diagnosed with COVID‐19

text: In this study, we collected a total of 610 hospitalized patients from Wuhan between February 2, 2020, and February 17, 2020. We reported a potentially high false negative rate of real‐time reverse‐transcriptase polymerase chain reaction (RT‐PCR) testing for SARS‐CoV‐2 in the 610 hospitalized patients clinically diagnosed with COVID‐19 during the 2019 outbreak. We also found that the RT‐PCR results from several tests at different points were variable from the same patients during the course of diagnosis and treatment of these patients. Our results indicate that in addition to the emphasis on RT‐PCR testing, clinical indicators such as computed tomography images should also be used not only for diagnosis and treatment but also for isolation, recovery/discharge, and transferring for hospitalized patients clinically diagnosed with COVID‐19 during the current epidemic. These results suggested the urgent needs for the standard of procedures of sampling from different anatomic sites, sample transportation, optimization of RT‐PCR, serology diagnosis/screening for SARS‐CoV‐2 infection, and distinct diagnosis from other respiratory diseases such as fluenza infections as well.


title: Modeling Control Strategies of Respiratory Pathogens

text: Effectively controlling infectious diseases requires quantitative comparisons of quarantine, infection control precautions, case identification and isolation, and immunization interventions. We used contact network epidemiology to predict the effect of various control policies for a mildly contagious disease, such as severe acute respiratory syndrome, and a moderately contagious disease, such as smallpox. The success of an intervention depends on the transmissibility of the disease and the contact pattern between persons within a community. The model predicts that use of face masks and general vaccination will only moderately affect the spread of mildly contagious diseases. In contrast, quarantine and ring vaccination can prevent the spread of a wide spectrum of diseases. Contact network epidemiology can provide valuable quantitative input to public health decisionmaking, even before a pathogen is well characterized.


title: Human coronavirus NL63, a new respiratory virus

text: From the mid-1960s onwards, it was believed that only two human coronavirus species infect humans: HCoV-229E and HCoV-OC43. Then, in 2003, a novel member of the coronavirus family was introduced into the human population: SARS-CoV, causing an aggressive lung disease. Fortunately, this virus was soon expelled from the human population, but it quickly became clear that the human coronavirus group contains more members then previously assumed, with HCoV-NL63 identified in 2004. Despite its recent discovery, ample results from HCoV-NL63 research have been described. We present an overview of the publications on this novel coronavirus.


title: COVID‐19 in elderly kidney transplant recipients

text: The SARS‐Cov‐2 infection disease (COVID‐19) pandemic has posed at risk the kidney transplant (KT) population, particularly the elderly recipients. From March‐12(th) until April‐4(th) 2020, we diagnosed COVID‐19 in 16 of our 324 KT patients aged ≥65 years old (4.9%). Many of them had had contact with healthcare facilities in the month prior to infection. Median time of symptom onset to admission was 7 days. All presented with fever and all but one with pneumonia. Up to 33% showed renal graft dysfunction. At infection diagnosis, mTOR inhibitors or mycophenolate were withdrawn. Tacrolimus was withdrawn in 70%. The main treatment combination was hydroxychloroquine and azithromycin. A subset of patients was treated with anti‐retroviral and tocilizumab. Short‐term fatality rate was 50% at a median time since admission of 3 days. Those who died were more frequently obese, frail and had underlying heart disease. Although a higher respiratory rate was observed at admission in nonsurvivors, symptoms at presentation were similar between both groups. Patients who died were more anemic, lymphopenic and showed higher D‐dimer, C‐reactive protein, and IL‐6 at their first tests. COVID‐19 is frequent among the elderly KT population and associates a very early and high mortality rate.


title: Chapter 27 Personalized Medicine of Alzheimer’s Disease

text: Abstract Alzheimer’s disease (AD) is a major problem of health and disability, with a relevant economic impact on society (e.g., €177 billion in Europe). Despite important advances in pathogenesis, diagnosis, and treatment, The primary causes of AD remain elusive, accurate biomarkers are not well characterized, and available pharmacological treatments are not cost-effective. As a complex disorder, AD is polygenic and multifactorial: hundreds of defective genes distributed across the human genome may contribute to its pathogenesis (with the participation of diverse environmental factors, cerebrovascular dysfunction, and epigenetic phenomena) and lead to amyloid deposition, neurofibrillary tangle formation, and premature neuronal death. Future perspectives for the global management of AD predict that structural and functional genomics and proteomics may help in the search for reliable biomarkers, and that pharmacogenomics may be an option in optimizing drug development and therapeutics.


title: The common cold

text: Summary Despite great advances in medicine, the common cold continues to be a great burden on society in terms of human suffering and economic losses. Of the several viruses that cause the disease, the role of rhinoviruses is most prominent. About a quarter of all colds are still without proven cause, and the recent discovery of human metapneumovirus suggests that other viruses could remain undiscovered. Research into the inflammatory mechanisms of the common cold has elucidated the complexity of the virus-host relation. Increasing evidence is also available for the central role of viruses in predisposing to complications. New antivirals for the treatment of colds are being developed, but optimum use of these agents would require rapid detection of the specific virus causing the infection. Although vaccines against many respiratory viruses could also become available, the ultimate prevention of the common cold seems to remain a distant aim.


Using a CO(2) detector to confirm endotracheal intubation in SARS patients


title: Rapid detection of the Streptococcus mutans cnm gene by loop-mediated isothermal amplification

text: This study investigated a method using loop-mediated isothermal amplification (LAMP) for the rapid detection of cnm-positive Streptococcus mutans (S. mutans) associated with cerebral microhemorrhage. LAMP amplified the cnm gene plasmid vector, but not human or microbial genomic DNA. The cnm DNA of the cnm-positive S. mutans strain was detected in saliva without DNA extraction after 1 day of culture. This method resulted in a cnm-positive rate of 26.4% in 102 samples, which was higher than that obtained with conventional PCR. In conclusion, LAMP may be used for the detection of cnm-positive S. mutans in a large number of samples.


The COVID‐19 outbreak and rheumatologic skin diseases


title: Efficacy, safety and cost‐effectiveness of hydroxychloroquine in children with COVID‐19: A call for evidence

text: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses a serious threat to public health and local economies around the globe. This has created an urgent need to identify effective medications for its prevention and treatment (1). Among these treatments, the off-label use of hydroxychloroquine (HCQ), a less toxic derivate of chloroquine, has become a common practice among clinicians, including pediatricians, despite lack of evidence of its clinical efficacy for this indication (especially for pediatric patients) at present time (2).


title: Type I Interferon Regulates the Expression of Long Non-Coding RNAs

text: Interferons (IFNs) are key players in the antiviral response. IFN sensing by the cell activates transcription of IFN-stimulated genes (ISGs) able to induce an antiviral state by affecting viral replication and release. IFN also induces the expression of ISGs that function as negative regulators to limit the strength and duration of IFN response. The ISGs identified so far belong to coding genes. However, only a small proportion of the transcriptome corresponds to coding transcripts and it has been estimated that there could be as many coding as long non-coding RNAs (lncRNAs). To address whether IFN can also regulate the expression of lncRNAs, we analyzed the transcriptome of HuH7 cells treated or not with IFNα2 by expression arrays. Analysis of the arrays showed increased levels of several well-characterized coding genes that respond to IFN both at early or late times. Furthermore, we identified several IFN-stimulated or -downregulated lncRNAs (ISRs and IDRs). Further validation showed that ISR2, 8, and 12 expression mimics that of their neighboring genes GBP1, IRF1, and IL6, respectively, all related to the IFN response. These genes are induced in response to different doses of IFNα2 in different cell lines at early (ISR2 or 8) or later (ISR12) time points. IFNβ also induced the expression of these lncRNAs. ISR2 and 8 were also induced by an influenza virus unable to block the IFN response but not by other wild-type lytic viruses tested. Surprisingly, both ISR2 and 8 were significantly upregulated in cultured cells and livers from patients infected with HCV. Increased levels of ISR2 were also detected in patients chronically infected with HIV. This is relevant as genome-wide guilt-by-association studies predict that ISR2, 8, and 12 may function in viral processes, in the IFN pathway and the antiviral response. Therefore, we propose that these lncRNAs could be induced by IFN to function as positive or negative regulators of the antiviral response.


title: Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial

text: Summary Background No specific antiviral drug has been proven effective for treatment of patients with severe coronavirus disease 2019 (COVID-19). Remdesivir (GS-5734), a nucleoside analogue prodrug, has inhibitory effects on pathogenic animal and human coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, and inhibits Middle East respiratory syndrome coronavirus, SARS-CoV-1, and SARS-CoV-2 replication in animal models. Methods We did a randomised, double-blind, placebo-controlled, multicentre trial at ten hospitals in Hubei, China. Eligible patients were adults (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia. Patients were randomly assigned in a 2:1 ratio to intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2–10 in single daily infusions) or the same volume of placebo infusions for 10 days. Patients were permitted concomitant use of lopinavir–ritonavir, interferons, and corticosteroids. The primary endpoint was time to clinical improvement up to day 28, defined as the time (in days) from randomisation to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first. Primary analysis was done in the intention-to-treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04257656. Findings Between Feb 6, 2020, and March 12, 2020, 237 patients were enrolled and randomly assigned to a treatment group (158 to remdesivir and 79 to placebo); one patient in the placebo group who withdrew after randomisation was not included in the ITT population. Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1·23 [95% CI 0·87–1·75]). Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less (hazard ratio 1·52 [0·95–2·43]). Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early. Interpretation In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies. Funding Chinese Academy of Medical Sciences Emergency Project of COVID-19, National Key Research and Development Program of China, the Beijing Science and Technology Project.


title: Infection and the etiology and pathogenesis of multiple sclerosis

text: Multiple sclerosis (MS) currently defies clinical and scientific definitions, and carries a prognosis that remains practically unchanged despite many years of intensive research. Although the prevailing dogma is that MS is an immune-mediated condition, it fulfills none of the criteria of an autoimmune disease. On the other hand, there is enough significant data to suggest that infectious agents(s) could be involved in either direct damage to the white matter or induce inflammatory responses that secondarily affect the brain. Our goal here is to review the data supporting the possibility that infection has a critical role in the disease, examine the list of potential candidates that have been suggested, and outline an approach regarding the potential role of infectious agents in the etiology and pathogenesis of MS.


title: Ten years’ experience with year-round active surveillance of up to 19 respiratory pathogens in children

text: INTRODUCTION: Surveillance systems for acute respiratory infections (ARI) in children currently are often limited in terms of the panel of pathogens and the age range investigated or are only syndromic and at times only active in the winter season. METHODS: Within PID-ARI.net, a research network for ARI in children in Germany, an active, year-round surveillance system was formed in three regions from north to south for population-based analysis. Children from birth to 16 years of age were included and up to 19 noncolonizing airway pathogens were tested for with multiplex RT-PCR. RESULTS: In the 10-year period from July 1996 to June 2006, a total of 18,899 samples were tested. The positive rate increased with the size of the test panel to up to 72.9%. Picornaviruses (35–39%), paramyxoviruses (23–28%) and orthomyxoviruses (5.8–12.5%) comprised the highest fraction. Reoviruses and Legionella pneumophila were not found at all and Chlamydia pneumoniae and Bordetella parapertussis only rarely. Respiratory syncytial virus and parainfluenza virus (PIV) type 3 were anticyclical in rhythmicity with metapneumovirus and PIV1 and PIV2. The age medians per pathogen depended predominantly upon the attack rate and interepidemic intervals. CONCLUSION: Active surveillance systems for ARI are superior to passive systems. They should be pathogen-specific and comprehensive for viruses and bacteria and age ranges. They should be population-based and multilevel to avoid bias. The impact of atypical bacteria in children was highly overestimated in earlier studies.


title: Assessing the spreading potential of an undetected case of COVID-19 in orthopaedic surgery

text: BACKGROUND: With the novel coronavirus-induced disease (COVID-19), there is the fear of nosocomial infections and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmissions to healthcare workers (HCW). We report the case of a 64-year-old male patient who underwent explantation of a shoulder prosthesis due to a periprosthetic infection. He was tested SARS-CoV-2 positive 7 days after admission to the orthopaedic department following strict infection control measures, routinely including screening all patients for multi-drug-resistant organism (MDRO) colonization upon admission. Aim of our study is to report on the spreading potential of SARS-CoV-2 in a healthcare setting if standard contact precautions and infection control measures have been established. METHODS: All HCW with exposure to the patient from day of admission until confirmed diagnosis of COVID-19 were identified and underwent oropharyngeal swab testing for SARS‐CoV‐2 by real-time RT-PCR. RESULTS: Sixty-six HCW were identified: nine orthopaedic surgeons, four anaesthesiologists, 25 orthopaedic nurses, five nurse anesthetists, eight scrub nurses, five nursing students, two medical assistants and seven service employees. Fourteen HCW (21%) showed clinical symptoms compatible with a SARS-CoV-2 infection: cough (n = 4), sore throat (n = 3), nasal congestion (n = 3), dyspnea (n = 2), fever (n = 1), headache and myalgia (n = 1). SARS-CoV-2 was not detected in any of the 66 HCW. CONCLUSION: Hygienic measures and contact precautions, aimed at preventing the spread of MRDO, may have helped to prevent a SARS-CoV-2 transmission to HCW—despite high-risk exposure during intubation, surgical treatment and general care. LEVEL OF EVIDENCE: IV, case series.


title: Global Reach of an Online COVID-19 Course in Multiple Languages on OpenWHO in the First Quarter of 2020: Analysis of Platform Use Data

text: BACKGROUND: At the onset of the coronavirus outbreak, the World Health Organization’s (WHO) Health Emergencies Learning and Capacity Development Unit, together with the WHO’s health technical lead on coronaviruses, developed a massive open online course within 3 weeks as part of the global response to the emergency. The introductory coronavirus disease (COVID‑19) course was launched on January 26, 2020, on the health emergencies learning platform OpenWHO.org. OBJECTIVE: The aim of this paper is to investigate the geographic reach of different language courses accessed by a worldwide audience seeking information on COVID-19. Users’ professional identities and backgrounds were explored to inform course owners on the use case. The course was developed and delivered via the open-access learning platform OpenWHO.org. The self-paced resources are available in a total of 13 languages and were produced between January 26 and March 25, 2020. METHODS: Data were collected from the online courses’ statistical data and metrics reporting system on the OpenWHO platform. User patterns and locations were analyzed based on Google Analytics and the platform’s own statistics capabilities, and data sets were overlaid. This analysis was conducted based on user location, with the data disaggregated according to the six WHO regions, the top 10 countries, and the proportion of use for each language version. Data included affiliation, gender, age, and other parameters for 32.43% (52,214/161,007) of the users who indicated their background. RESULTS: As of March 25, 2020, the introductory COVID-19 course totaled 232,890 enrollments across all languages. The Spanish language course was comprised of more than half (n=118,754, 50.99%) of all course enrollments, and the English language course was comprised of 38.21% (n=88,988) of enrollments. The WHO’s Region of the Americas accounted for most of the course enrollments, with more than 72.47% (138,503/191,130) enrollment across all languages. Other regions were more evenly distributed with less than 10% enrollment for each. A total of 32.43% (52,214/161,007) of users specified a professional affiliation by choosing from the 12 most common backgrounds in the OpenWHO user profiles. Before the COVID-19 pandemic, users were spread over the 11 distinct affiliations, with a small fraction of users identifying themselves as “Other.” With the COVID-19 introductory course, the largest number of users selected “Other” (16,527/52,214, 31.65%), suggesting a large number of users who were not health professionals or academics. The top 10 countries with the most users across all languages were Argentina, Chile, Colombia, Ecuador, India, Mexico, Peru, Spain, the United Kingdom, and the United States. CONCLUSIONS: The online course has addressed a worldwide learning need by providing WHO’s technical guidance packaged in simple formats for access and use. The learning material development was expedited to meet the onset of the epidemic. Initial data suggest that the various language versions of the course, in particular Spanish, have reached new user groups, fulfilling the platform’s aim of providing learning everywhere to anyone that is interested. User surveys will be carried out to measure the real impact.


title: Virology of infantile chronic recurrent parotitis in Santiago de Chile

text: Infantile chronic recurrent parotitis (ICRP) has been attributed to multiple causes, including viral infections, and therefore its treatment remains empirical. Our aim was to evaluate the involvement of respiratory and oropharyngeal viruses in acute episodes of ICRP. Seventy children were studied, 50 patients and 20 age‐matched controls, in a 2‐year follow‐up study. Saliva samples were taken from the parotid duct and analyzed by viral isolation and immunofluorescence for adenovirus (Ad), respiratory sincitial virus (RSV), parainfluenza virus (PI), influenza virus (Flu), Cytomegalovirus (CMV), and herpes simplex virus (HSV). Paired sera samples were tested by ELISA for anti‐Epstein‐Barr virus (EBV) IgG and anti‐mumps IgM and IgG. Viral infections were detected in 7/50 (14%) cases of the ICRP group: one CMV; 2 Enteroviruses isolated in human embryonic lung fibroblast cells; 1 Flu A; and 3 mumps virus. No EBV seroconversions were detected. In the control group, 2 out of the 20 children had an asymptomatic mumps positive IgM titer. Our data indicate that the main respiratory and oropharyngeal viruses are not the cause of acute episodes of ICRP in Chilean children. J. Med. Virol. 70:459–462, 2003. © 2003 Wiley‐Liss, Inc.


ARIA‐EAACI statement on Asthma and COVID‐19 (June 2, 2020)


title: Urban‐Rural Polarisation in Times of the Corona Outbreak? The Early Demographic and Geographic Patterns of the SARS‐CoV‐2 Epidemic in the Netherlands

text: The global health crisis due to the pandemic of the SARS‐CoV‐2 is associated with processes of urbanisation and globalisation. Globally well‐connected areas with high population densities are hence expected to be disproportionately affected by COVID‐19. This paper investigates the role of population density within the Netherlands, comparing hospitalisation and mortality related to COVID‐19 across municipalities. The paper finds that infections, hospitalisation and mortality related to COVID‐19 are not clearly correlated with the population density or urbanity of the municipality, also when controlling for age and public health factors. The paper concludes that while the public debate stresses the elevated risk of infections in cities, due to transgressive behaviour, the evidence in this paper suggests that the geography of the epidemic in the Netherlands is more complex. It speculates that the variation in urbanisation in most of the country might just be too small to expect significant differences.


ACE2 Gene Polymorphisms Do Not Affect Outcome of Severe Acute Respiratory Syndrome


Recommending wearing a mask without masking the truth


title: Etiology of community‐acquired pneumonia in 1500 hospitalized children

text: Childhood community‐acquired pneumonia (CAP) is a common illness; however, comprehensive studies of hospitalizations for CAP among children in China based on prospective and multicenter data collection are limited. The aim of this investigation was to determine the respiratory pathogens responsible for CAP in hospitalized children. From January to December 2015, oropharyngeal swabs and blood serum were collected from hospitalized children with CAP symptoms ranging in age from 6 months to 14 years at 10 hospitals across China. We used immunofluorescence to detect antibodies for eight respiratory viruses and passive agglutination to detect specific IgM against Mycoplasma pneumoniae (M. pneumoniae). Of 1500 children presenting with CAP, 691 (46.1%) tested positive for at least one pathogen (virus or M. pneumoniae). M. pneumoniae (32.4%) was detected most frequently, followed by respiratory syncytial virus (11.5%), adenovirus (5.0%), influenza A virus (4.1 %), influenza B virus (3.4%), parainfluenza virus types 2 and 3 type (3.1 %), parainfluenza virus type 1 (2.9%), and human metapneumovirus (0.3%). Co‐infections were identified in 128 (18.5%) of the 691 cases. These data provide a better understanding of viral etiology and M. pneumoniae in CAP in children between 6 months and 14 years in China. More study of the etiologic investigations that would further aid the management of pneumonia is required. With effective immunization for RSV, ADV, and M. pneumoniae infections, more than one‐half of the pneumonia cases in this study could have been prevented.


Reactivation of COVID-19 pneumonia: a report of two cases


Children returning to schools following COVID-19: A balance of probabilities – Letter to the Editor


title: Procedures for Flow Cytometry‐Based Sorting of Unfixed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) Infected Cells and Other Infectious Agents

text: In response to the recent COVID‐19 pandemic, many laboratories are involved in research supporting SARS‐CoV‐2 vaccine development and clinical trials. Flow cytometry laboratories will be responsible for a large part of this effort by sorting unfixed antigen‐specific lymphocytes. Therefore, it is critical and timely that we have an understanding of risk assessment and established procedures of infectious cell sorting. Here we present procedures covering the biosafety aspects of sorting unfixed SARS‐CoV‐2‐infected cells and other infectious agents of similar risk level. These procedures follow the ISAC Biosafety Committee guidelines and were recently approved by the National Institutes of Health Institutional Biosafety Committee for sorting SARS‐CoV‐2‐infected cells. © 2020 International Society for Advancement of Cytometry


title: Rapid Field Immunoassay for Detecting Antibody to Sin Nombre Virus in Deer Mice

text: We developed a 1-hour field enzyme immunoassay (EIA) for detecting antibody to Sin Nombre virus in deer mice (Peromyscus maniculatus). The assay specificity and sensitivity were comparable to those of a standard EIA. This test will permit identification of rodents with antibody to this and perhaps other hantaviruses.


title: Evaluation of Lassa antiviral compound ST-193 in a guinea pig model

text: Abstract Lassa virus (LASV), a member of the Arenaviridae family, causes a viral hemorrhagic fever endemic to West Africa, where as many as 300,000 infections occur per year. Presently, there are no FDA-approved LASV-specific vaccines or antiviral agents, although the antiviral drug ribavirin has shown some efficacy. A recently identified small-molecule inhibitor of arenavirus entry, ST-193, exhibits submicromolar antiviral activity in vitro. To determine the antiviral utility of ST-193 in vivo, we tested the efficacy of this compound in the LASV guinea pig model. Four groups of strain 13 guinea pigs were administered 25 or 80mg/kg ST-193, 25mg/kg of ribavirin, or the vehicle by the intraperitoneal (i.p.) route before infection with a lethal dose of LASV, strain Josiah, and continuing once daily for 14 days. Control animals exhibited severe disease, becoming moribund between days 10 and 15 postinfection. ST-193-treated animals exhibited fewer signs of disease and enhanced survival when compared to the ribavirin or vehicle groups. Body temperatures in all groups were elevated by day 9, but returned to normal by day 19 postinfection in the majority of ST-193-treated animals. ST-193 treatment mediated a 2–3-log reduction in viremia relative to vehicle-treated controls. The overall survival rate for the ST-193-treated guinea pigs was 62.5% (10/16) compared with 0% in the ribavirin (0/8) and vehicle (0/7) groups. These data suggest that ST-193 may serve as an improved candidate for the treatment of Lassa fever.


title: Collection of Viable Aerosolized Influenza Virus and Other Respiratory Viruses in a Student Health Care Center through Water-Based Condensation Growth

text: The dynamics and significance of aerosol transmission of respiratory viruses are still controversial, for the major reasons that virus aerosols are inefficiently collected by commonly used air samplers and that the collected viruses are inactivated by the collection method. Without knowledge of virus viability, infection risk analyses lack accuracy. This pilot study was performed to (i) determine whether infectious (viable) respiratory viruses in aerosols could be collected from air in a real world environment by the viable virus aerosol sampler (VIVAS), (ii) compare and contrast the efficacy of the standard bioaerosol sampler, the BioSampler, with that of the VIVAS for the collection of airborne viruses in a real world environment, and (iii) gain insights for the use of the VIVAS for respiratory virus sampling. The VIVAS operates via a water vapor condensation process to enlarge aerosolized virus particles to facilitate their capture. A variety of viable human respiratory viruses, including influenza A H1N1 and H3N2 viruses and influenza B viruses, were collected by the VIVAS located at least 2 m from seated patients, during a late-onset 2016 influenza virus outbreak. Whereas the BioSampler when operated following our optimized parameters also collected virus aerosols, it was nevertheless overall less successful based on a lower frequency of virus isolation in most cases. This side-by-side comparison highlights some limitations of past studies based on impingement-based sampling, which may have generated false-negative results due to either poor collection efficiency and/or virus inactivation due to the collection process. IMPORTANCE The significance of virus aerosols in the natural transmission of respiratory diseases has been a contentious issue, primarily because it is difficult to collect or sample virus aerosols using currently available air sampling devices. We tested a new air sampler based on water vapor condensation for efficient sampling of viable airborne respiratory viruses in a student health care center as a model of a real world environment. The new sampler outperformed the industry standard device (the SKC BioSampler) in the collection of natural virus aerosols and in maintaining virus viability. These results using the VIVAS indicate that respiratory virus aerosols are more prevalent and potentially pose a greater inhalation biohazard than previously thought. The VIVAS thus appears to be a useful apparatus for microbiology air quality tests related to the detection of viable airborne viruses.


Simultaneous coinfection with Cryptococcus neoformans and Mycobacterium tuberculosis in an adult


title: A Hadoop-Based Platform for Patient Classification and Disease Diagnosis in Healthcare Applications

text: Nowadays, the increasing number of patients accompanied with the emergence of new symptoms and diseases makes heath monitoring and assessment a complicated task for medical staff and hospitals. Indeed, the processing of big and heterogeneous data collected by biomedical sensors along with the need of patients’ classification and disease diagnosis become major challenges for several health-based sensing applications. Thus, the combination between remote sensing devices and the big data technologies have been proven as an efficient and low cost solution for healthcare applications. In this paper, we propose a robust big data analytics platform for real time patient monitoring and decision making to help both hospital and medical staff. The proposed platform relies on big data technologies and data analysis techniques and consists of four layers: real time patient monitoring, real time decision and data storage, patient classification and disease diagnosis, and data retrieval and visualization. To evaluate the performance of our platform, we implemented our platform based on the Hadoop ecosystem and we applied the proposed algorithms over real health data. The obtained results show the effectiveness of our platform in terms of efficiently performing patient classification and disease diagnosis in healthcare applications.


title: An AI approach to COVID-19 infection risk assessment in virtual visits: a case report

text: OBJECTIVE: In an effort to improve the efficiency of computer algorithms applied to screening for COVID-19 testing, we used natural language processing (NLP) and artificial intelligence (AI)-based methods with unstructured patient data collected through telehealth visits. METHODS: After segmenting and parsing documents, we conducted analysis of overrepresented words in patient symptoms. We then developed a word embedding-based convolutional neural network for predicting COVID-19 test results based on patients’ self-reported symptoms. RESULTS: Text analytics revealed that concepts such as “smell” and “taste” were more prevalent than expected in patients testing positive. As a result, screening algorithms were adapted to include these symptoms. The deep learning model yielded an AUC of 0.729 for predicting positive results and was subsequently applied to prioritize testing appointment scheduling. DISCUSSION: Informatics tools such as NLP and AI methods can have significant clinical impacts when applied to data streams early in the development of clinical systems for outbreak response.


COVID‐19, leadership and lessons from physics


title: Infectious bronchitis virus regulates cellular stress granule signaling

text: Viruses must hijack cellular translation machinery to efficiently express viral genes. In many cases, this is impeded by cellular stress responses. These stress responses swiftly relocate and repurpose translation machinery, resulting in global inhibition of translation and the aggregation of stalled 48S mRNPs into cytoplasmic foci called stress granules. This results in translational silencing of all mRNAs excluding those beneficial for the cell to resolve the specific stress. For example, expression of antiviral factors is maintained during viral infection. Here we investigated stress granule regulation by Gammacoronavirus infectious bronchitis virus (IBV), which causes the economically important poultry disease, infectious bronchitis. Interestingly, we found that IBV is able to inhibit multiple cellular stress granule signaling pathways whilst at the same time IBV replication also results in induction of seemingly canonical stress granules in a proportion of infected cells. Moreover, IBV infection uncouples translational repression and stress granule formation and both processes are independent of eIF2α phosphorylation. These results provide novel insights into how IBV modulates cellular translation and antiviral stress signaling.


title: External quality assessment for the molecular detection of MERS-CoV in China

text: Abstract Background In May 2015, an imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection occurred in China, so rapid and reliable diagnosis of suspected cases was necessary. Objectives An external quality assessment (EQA) program for the molecular detection of MERS-CoV was organized by the National Center for Clinical Laboratories (NCCL). Study design MS2 virus-like particles (VLPs) encapsulating specific RNA sequences of MERS-CoV were prepared as positive specimens. The assessment panel, which comprised of three negative and seven positive samples with different concentrations of VLPs, was distributed to 56 laboratories from 16 provinces, municipalities, or autonomous regions for molecular detection. Results Among the received data sets, three employed an in-house-developed real-time reverse-transcription polymerase chain reaction (rRT-PCR) assay and the others applied various commercial rRT-PCR kits. Overall, the majority of laboratories (46/56, 82.1%) could achieve 100% accuracy for MERS-CoV detection, but three laboratories (5.4%) still had room for improvement. Consequently, all negative samples were identified correctly, reaching 100% specificity. The false-negative rate was 3.1%, and most of the false-negative results were obtained from samples with relatively low concentration, indicating an urgent need to improve detection in weak-positive specimens. Conclusions The majority of participants possessed reliable diagnostic capacity for the detection of MERS-CoV. Moreover, EQA is indispensable because it can help enhance the diagnostic capability for the surveillance of MERS-CoV infections and allow comparison of the results among different laboratories.


title: Sustained Viremia and High Viral Load in Respiratory Tract Secretions Are Predictors for Death in Immunocompetent Adults with Adenovirus Pneumonia

text: The predictors for fatal adenovirus (AdV) pneumonia among immunocompetent adults are unclear. Laboratory-confirmed, hospitalized AdV pneumonia adults were prospectively enrolled in Beijing Chao-Yang hospital from March to June 2013. Clinical data and serial whole blood and respiratory tract secretions from such patients were collected. Quantitative real-time polymerase chain reaction was performed to quantify the viral load. A total of 14 AdV pneumonia cases were consecutively enrolled, and four of them were fatal. Ten cases were caused by AdV-55, three by AdV-7 and one by AdV-3. There were no differences in age, gender or underlying diseases between the patients in the fatal cases and surviving cases. At admission (on day 5–7 after illness onset), the patients in fatal cases presented higher initial viral loads in respiratory tract secretions (8.578 ± 2.115 vs 6.263 ± 1.225 Log(10) copies/ml, p = 0.023). All patients in fatal cases presented with viremia on day 12–14 (100% vs 66.7%, p = 0.017). A higher initial viral load in the respiratory tract and sustained viremia (more than 2 weeks) may be predictors for fatal clinical outcomes.


title: Detection of astroviruses in feces of a cat with diarrhea

text: Astroviruses were detected by electron microscopy in the feces from a 4 month old kitten with diarrhea. The mean diameter of the viral particles was 28.7 nm, and they showed characteristic five- or six-pointed star-shaped surface configurations. The clinical disease manifested by the cat and the observed morphology of the viral particles are consistent with previous reports on astroviruses of other species.


title: Transport and Management of Patients With Confirmed or Suspected Ebola Virus Disease

text: The foundation of safe care for patients with confirmed or suspected Ebola virus disease is effective infection control practice, which requires implementation of appropriate administrative policies, work practices, and environmental controls, accompanied by focused education, training, and supervision. In 2002, Emory University partnered with the Centers for Disease Control and Prevention to develop a capability for the evaluation and management of individuals with serious communicable disease. In 2005, the University of Nebraska developed a similar isolation capability. In each case, the hospitals partnered with emergency medical services (EMS) professionals to ensure safe out-of-hospital transport and management of their patients. The objectives of these hospital and out-of-hospital collaborations were to close education, training, and practice gaps to best facilitate the care for patients with serious communicable disease while ensuring the safety of the medics and the general public through meticulous implementation of infection control practices as recommended by Centers for Disease Control and Prevention. The description of practices implemented by EMS teams in these communities for the transport of patients with confirmed Ebola virus disease is shared so that others might more readily implement these practices, policies, and procedures as applicable to their mission requirements and system design. Transport of patients with relevant travel history and development of illness (persons under investigation) is also included.


COVID-19 - Journal de bord - 10/03/2020: Pandémie virale: s’inquiéter, organiser, prévoir


Immunology of Multiple Sclerosis


title: Chapter 501 Rubella Virus Non-Structural Protease

text: The third edition of the Handbook of Proteolytic Enzymes aims to be a comprehensive reference work for the enzymes that cleave proteins and peptides, and contains over 800 chapters. Each chapter is organized into sections describing the name and history, activity and specificity, structural chemistry, preparation, biological aspects, and distinguishing features for a specific peptidase. The subject of Chapter 501 is Rubella Virus Non-structural Protease. Keywords: Alphavirus protease, Ca binding motif, calmodulin binding motif, catalytic Cys-His dyad, papain-like cysteine protease, regulation of virus replication, regulation of virus RNA polymerase activity, togavirus protease, virus evolution, virus-encoded protease, virus peptidase, Zn binding motif.


title: COVID 19 can spread through breathing, talking, study estimates

text: Abstract The COVID 19 pandemic has become a major threat to humankind infecting millions world-wide. This virus can be spread through breathing, talking. During sneezing, breathing and loud conservation, it releases about 1000 micro droplets which drift in the air. These micro droplets carry many viruses and it might act as a third route of infection for COVID 19 infection. The type of infection is known as micro droplets infection.


title: Short-term effects of weather parameters on COVID-19 morbidity in select US cities

text: Abstract Little is known about the environmental conditions that drive the spatiotemporal patterns of SARS-CoV-2, and preliminary research suggests an association with weather parameters. However, the relationship with temperature and humidity is not yet apparent for COVID-19 cases in US cities first impacted. The objective of this study is to evaluate the association between COVID-19 cases and weather parameters in select US cities. A case-crossover design with a distributed lag nonlinear model was used to evaluate the contribution of ambient temperature and specific humidity on COVID-19 cases in select US cities. The case-crossover examines each COVID case as its own control at different time periods (before and after transmission occurred). We modeled the effect of temperature and humidity on COVID-19 transmission using a lag period of 7 days. A subset of 8 cities were evaluated for the relationship with weather parameters and 5 cities were evaluated in detail. Short-term exposure to humidity was positively associated with COVID-19 transmission in 4 cities. The associations were small with ¾ cities exhibiting higher COVID19 transmission with specific humidity that ranged from 6 to 9 g/kg. Our results suggest that weather should be considered in infectious disease modeling efforts and future work is needed over a longer time period and across different locations to clearly establish the weather-COVID19 relationship.


SARS Patients and Need for Treatment


title: Bariatric surgery and the COVID-19 pandemic: SICOB recommendations on how to perform surgery during the outbreak and when to resume the activities in phase 2 of lockdown

text: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its related disease, coronavirus disease 2019 (COVID-19), has been rapidly spreading all over the world and is responsible for the current pandemic. The current pandemic has found the Italian national health system unprepared to provide an appropriate and prompt response, heavily affecting surgical activities. Based on the limited data available in the literature and personal experiences, the Società Italiana di Chirurgia dell’OBesità e Malattie Metaboliche (SICOB) provides recommendations regarding the triage of bariatric surgical procedures during the COVID-19 pandemic defining a dedicated path for surgery in morbidly obese patients with known or suspected COVID-19 who may require emergency operations. Finally, the current paper delineates a strategy to resume outpatient visits and elective bariatric surgery once the acute phase of the pandemic is over. Models developed during the COVID-19 crisis should be integrated into hospital practices for future use in similar scenarios. Surgeons are presented with a golden opportunity to embrace systemic change and to drive their professional future.


title: Reconstruction and prediction of viral disease epidemics

text: A growing number of infectious pathogens are spreading among geographic regions. Some pathogens that were previously not considered to pose a general threat to human health have emerged at regional and global scales, such as Zika and Ebola Virus Disease. Other pathogens, such as yellow fever virus, were previously thought to be under control but have recently re-emerged, causing new challenges to public health organisations. A wide array of new modelling techniques, aided by increased computing capabilities, novel diagnostic tools, and the increased speed and availability of genomic sequencing allow researchers to identify new pathogens more rapidly, assess the likelihood of geographic spread, and quantify the speed of human-to-human transmission. Despite some initial successes in predicting the spread of acute viral infections, the practicalities and sustainability of such approaches will need to be evaluated in the context of public health responses.


title: Effectiveness of Interventions to Reduce Contact Rates during a Simulated Influenza Pandemic

text: Measures to decrease contact between persons during an influenza pandemic have been included in pandemic response plans. We used stochastic simulation models to explore the effects of school closings, voluntary confinements of ill persons and their household contacts, and reductions in contacts among long-term care facility (LTCF) residents on pandemic-related illness and deaths. Our findings suggest that school closings would not have a substantial effect on pandemic-related outcomes in the absence of measures to reduce out-of-school contacts. However, if persons with influenzalike symptoms and their household contacts were encouraged to stay home, then rates of illness and death might be reduced by ≈50%. By preventing ill LTCF residents from making contact with other residents, illness and deaths in this vulnerable population might be reduced by ≈60%. Restricting the activities of infected persons early in a pandemic could decrease negative health impact.