title: Molecular characterization of noroviruses detected in diarrheic stools of Michigan and Wisconsin dairy calves: circulation of two distinct subgroups

text: Abstract Noroviruses have emerged as the leading worldwide cause of acute non-bacterial gastroenteritis in humans. The presence of noroviruses in diarrheic stool samples from calves on Michigan and Wisconsin dairy farms was investigated by RT-PCR. Norovirus-positive samples were found on all eight farms studied in Michigan and on 2 out of 14 farms in Wisconsin. Phylogenetic analyses of partial polymerase and capsid sequences, derived for a subset of these bovine noroviruses, showed that these strains formed a group which is genetically distinct from the human noroviruses, but more closely related to genogroup I than to genogroup II human noroviruses. Examination of 2 full and 10 additional partial capsid (ORF2) sequences of these bovine strains revealed the presence of two genetic subgroups or clusters of bovine noroviruses circulating on Michigan and Wisconsin farms. One subgroup is “Jena-like”, the other “Newbury agent-2-like”.


title: Excess drug prescriptions during influenza and RSV seasons in the Netherlands: Potential implications for extended influenza vaccination

text: Abstract Influenza and respiratory syncytial virus (RSV) infections are responsible for considerable morbidity, mortality and health-care resource use. For the Netherlands, we estimated age and risk-group specific numbers of antibiotics, otologicals and cardiovascular prescriptions per 10,000 person-years during periods with elevated activity of influenza or RSV, and compared these with peri-season rates. Data were taken from the University of Groningen in-house prescription database (www.iadb.nl) and virological surveillance for the period 1998–2006. During influenza and RSV periods excess antibiotic prescriptions were estimated for all age groups. In the age groups 0–1 and 2–4 years, excess antibiotic prescriptions during periods with elevated RSV activity (65% and 59% of peri-seasonal rates) exceeded the surpluses estimated during the influenza-activity periods (24% and 34% of peri-seasonal rates) while for otologicals excess prescriptions were higher for influenza (22% and 27%) than for RSV (14% and 17%). Among persons of 50 years and older, notably those without medical high-risk conditions, excess prescriptions for cardiovascular medications were estimated during the influenza periods at approximately 10% (this was also already seen in persons aged 45–49). Our results may have implications for influenza vaccination policies. In particular, extension of influenza vaccination to groups of non-elderly adults and young children may lower excess prescriptions during these influenza periods for all three types of drug prescriptions investigated.


title: Discovery of a novel accessory protein NS7a encoded by porcine deltacoronavirus

text: Porcine deltacoronavirus (PDCoV) is an emerging swine enteric coronavirus. Bioinformatics predicts that PDCoV encodes two accessory proteins (NS6 and NS7), the species-specific proteins for coronavirus. In this study, four mAbs against the predicted NS7 were prepared by using the purified recombinant NS7 protein. Indirect immunofluorescence assay demonstrated that all mAbs recognized cells transfected with an NS7 expression construct or infected with PDCoV. Western blot showed that NS7-specific mAbs recognized an additional protein band of about 12 kDa from PDCoV-infected cell lysates but not from cells with the ectopic expression of NS7. Detailed analysis suggested that this additional protein band represented a novel accessory protein, termed NS7a, a 100 amino acid polypeptide identical to the 3′ end of NS7. Moreover, NS7a is encoded by a separate subgenomic mRNA with a non-canonical transcription regulatory sequence. In summary, our results identified a third accessory protein encoded by PDCoV, which will enhance our understanding of PDCoV.


Abstracts und ausgewählte Vorträge der 17. Jahrestagung der Deutschen Gesellschaft für Pädiatrische Infektiologie (DGPI) zusammen mit der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)


title: Strengthening epidemiologic investigation of infectious diseases in Korea: lessons from the Middle East Respiratory Syndrome outbreak

text: The recent outbreak of Middle East Respiratory Syndrome (MERS) coronavirus infection in Korea resulted in large socioeconomic losses. This provoked the Korean government and the general public to recognize the importance of having a well-established system against infectious diseases. Although epidemiologic investigation is one of the most important aspects of prevention, it has been pointed out that much needs to be improved in Korea. We review here the current status of the Korean epidemiologic service and suggest possible supplementation measures. We examine the current national preventive infrastructure, including human resources such as Epidemic Intelligence Service officers, its governmental management, and related policies. In addition, we describe the practical application of these resources to the recent MERS outbreak and the progress in preventive measures. The spread of MERS demonstrated that the general readiness for emerging infectious diseases in Korea is considerably low. We believe that it is essential to increase society’s investment in disease prevention. Fostering public health personnel, legislating management policies, and establishing research centers for emerging infectious diseases are potential solutions. Evaluating international preventive systems, developing cooperative measures, and initiating improvements are necessary. We evaluated the Korean epidemiologic investigation system and the public preventive measures against infectious diseases in light of the recent MERS outbreak. We suggest that governmental authorities in Korea enforce preventive policies, foster the development of highly qualified personnel, and increase investment in the public health domain of infectious disease prevention.


title: CT imaging features of 4121 patients with COVID‐19: A meta‐analysis

text: OBJECTIVE: We systematically reviewed the computed tomography (CT) imaging features of coronavirus disease 2019 (COVID‐19) to provide reference for clinical practice. METHODS: Our article comprehensively searched PubMed, FMRS, EMbase, CNKI, WanFang databases, and VIP databases to collect literatures about the CT imaging features of COVID‐19 from 1 January to 16 March 2020. Three reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies, and then, this meta‐analysis was performed by using Stata12.0 software. RESULTS: A total of 34 retrospective studies involving a total of 4121 patients with COVID‐19 were included. The results of the meta‐analysis showed that most patients presented bilateral lung involvement (73.8%, 95% confidence interval [CI]: 65.9%‐81.1%) or multilobar involvement (67.3%, 95% CI: 54.8%‐78.7%) and just little patients showed normal CT findings (8.4%). We found that the most common changes in lesion density were ground‐glass opacities (68.1%, 95% CI: 56.9%‐78.2%). Other changes in density included air bronchogram sign (44.7%), crazy‐paving pattern (35.6%), and consolidation (32.0%). Patchy (40.3%), spider web sign (39.5%), cord‐like (36.8%), and nodular (20.5%) were common lesion shapes in patients with COVID‐19. Pleural thickening (27.1%) was found in some patients. Lymphadenopathy (5.4%) and pleural effusion (5.3%) were rare. CONCLUSION: The lung lesions of patients with COVID‐19 were mostly bilateral lungs or multilobar involved. The most common chest CT findings were patchy and ground‐glass opacities. Some patients had air bronchogram, spider web sign, and cord‐like. Lymphadenopathy and pleural effusion were rare.


title: Health Care–Acquired Viral Respiratory Diseases

text: Health care–acquired viral respiratory infections are common and cause increased patient morbidity and mortality. Respiratory syncytial virus and influenza virus are frequently transmitted in the hospital setting. Studies report decreased nosocomial transmission when aggressive infection control measures are implemented with more success using a multicomponent approach. Influenza vaccination of health care personnel has been shown to further decrease rates of transmission, thus mandatory vaccination is becoming more common. This article focuses on the epidemiology, transmission, and control of health care–associated respiratory viral infections.


title: Heat shock proteins and superantigenic properties of bacteria from the gastrointestinal tract of patients with Kawasaki disease

text: We previously suggested that gut bacteria may be involved in the onset of Kawasaki disease (KD). In this study, we evaluated the production of heat shock proteins (hsps) and superantigens (sAgs) by microorganisms isolated from the jejunal mucosa of 19 children with KD in the acute phase and from 15 age-matched control children. We identified 13 strains of Gram-negative microbes from patients with KD; these microbes produced large amounts of hsp60 and induced pro-inflammatory cytokine production by peripheral blood mononuclear cells. The Gram-negative microbes also elicited endogenous hsp60 production, leading to the secretion of anti-inflammatory intereukin-10 (IL-10). We also identified 18 strains of Gram-positive cocci that had superantigenic properties and which induced the expansion of Vβ2 T cells in vitro. All bacteria identified in this study were antibiotic resistant. These data suggest that sAg and hsps produced by gut bacteria might be involved in KD.


title: Spatial spread of an epidemic through public transportation systems with a hub

text: Abstract This article investigates an epidemic spreading among several locations through a transportation system, with a hub connecting these locations. Public transportation is not only a bridge through which infections travel from one location to another but also a place where infections occur since individuals are typically in close proximity to each other due to the limited space in these systems. A mathematical model is constructed to study the spread of an infectious disease through such systems. A variant of the next generation method is proposed and used to provide upper and lower bounds of the basic reproduction number for the model. Our investigation indicates that increasing transportation efficiency, and improving sanitation and ventilation of the public transportation system decrease the chance of an outbreak occurring. Moreover, discouraging unnecessary travel during an epidemic also decreases the chance of an outbreak. However, reducing travel by infectives while allowing susceptibles to travel may not be enough to avoid an outbreak.


title: Is nicotine exposure linked to cardiopulmonary vulnerability to COVID‐19 in the general population?

text: The recent emergence of COVID‐19 has resulted in a worldwide crisis, with large populations locked down and transportation links severed. While approximately 80% of infected individuals have minimal symptoms, around 15–20% need to be hospitalized, greatly stressing global healthcare systems. As of March 10, the death rate appears to be about 3.4%, although this number is highly stratified among different populations. Here, we focus on those individuals who have been exposed to nicotine prior to their exposure to the virus. We predict that these individuals are ‘primed’ to be at higher risk because nicotine can directly impact the putative receptor for the virus (ACE2) and lead to deleterious signaling in lung epithelial cells.


title: Synthetic approaches toward stilbenes and their related structures

text: Compounds belonging to the stilbene family have gained remarkable significance in pharmaceutical as well as material chemistry. The current review covers the various synthetic approaches for the syntheses of stilbene scaffold and related structures over last 30 years. In addition, this review also highlights the role of stilbene intermediates used in the synthesis of important molecules with diverse applications in the field of pharmaceutics and material science.


title: 2018 international meeting of the Global Virus Network

text: Abstract The Global Virus Network (GVN) was established in 2011 to strengthen research and responses to emerging viral causes of human disease and to prepare against new viral pandemics. There are now 45 GVN Centers of Excellence and 7 Affiliate laboratories in 29 countries. The 10th International GVN meeting was held from November 28–30, 2018 in Veyrier du Lac, France and was co-hosted by the two GVN Centers of Excellence, the Mérieux Foundation and the University of Veterinary Medicine Hannover (TiHo). The theme of this 10th International GVN meeting was “Eradication and control of (re-) emerging viruses”. This report highlights the recent accomplishments of GVN researchers in several important areas of medical virology, including strategies for the eradication of smallpox, measles, polio, SARS and vector-borne or zoonotic infections, emergence and intervention strategies for retroviruses and arboviruses, preparedness for outbreaks of Filo- and other hemophilic viruses, pathogenesis, impact and prevention of respiratory viruses, as well as, viruses affecting the central and peripheral nervous system. Also threats in crisis settings like refugee camps were presented.


In Memoriam: Michael B. Gregg (1930–2008)


title: Nucleocapsid protein of SARS coronavirus tightly binds to human cyclophilin A

text: Abstract Severe acute respiratory syndrome coronavirus (SARS-CoV) is responsible for SARS infection. Nucleocapsid protein (NP) of SARS-CoV (SARS_NP) functions in enveloping the entire genomic RNA and interacts with viron structural proteins, thus playing important roles in the process of virus particle assembly and release. Protein–protein interaction analysis using bioinformatics tools indicated that SARS_NP may bind to human cyclophilin A (hCypA), and surface plasmon resonance (SPR) technology revealed this binding with the equilibrium dissociation constant ranging from 6 to 160nM. The probable binding sites of these two proteins were detected by modeling the three-dimensional structure of the SARS_NP–hCypA complex, from which the important interaction residue pairs between the proteins were deduced. Mutagenesis experiments were carried out for validating the binding model, whose correctness was assessed by the observed effects on the binding affinities between the proteins. The reliability of the binding sites derived by the molecular modeling was confirmed by the fact that the computationally predicted values of the relative free energies of the binding for SARS_NP (or hCypA) mutants to the wild-type hCypA (or SARS_NP) are in good agreement with the data determined by SPR. Such presently observed SARS_NP–hCypA interaction model might provide a new hint for facilitating the understanding of another possible SARS-CoV infection pathway against human cell.


title: A reflection on an adapted approach from face‐to‐face to telephone consultations in our Urology outpatient department during the COVID‐19 pandemic – a pathway for change to future practice?

text: The sudden and unanticipated COVID‐19 viral pandemic of 2020 and its profound impact on the NHS prompted an almost overnight change in the services we are able to offer our patients to fulfil clinical demands. From March 2020 we have changed outpatient appointments from face‐to‐face to telephone led consultations. We have performed an early review of this service to ensure its sustainability during the unknown duration of this current crisis and to establish its potential utility when normal services resume in the future. Our results show a patient satisfaction of 93% with 83% happy to have telephone follow‐up in the future and a clinician satisfaction of 82% in adequacy of the telephone consultation in making a clinical decision. Telephone clinics are a safe and efficient alternative to face‐to‐face outpatient consultations for many patients, particularly non‐complex benign follow‐ups.


title: CORONAVIRUS PROPAGATED FROM PATIENT WITH NON-BACTERIAL GASTROENTERITIS

text: Abstract A fæcal suspension from a patient with gastroenteritis, which contained large numbers of coronavirus particles when examined by electron microscopy, was inoculated into human embryo intestinal-organ cultures and primary human embryo-kidney monolayers. In the organ cultures, the villous epithelium became detached and large numbers of coronavirus particles were seen by electron microscopy both in the medium and in thin sections of the intestinal epithelial cells, where the virus appeared to be multiplying. In organ cultures and in human embryo-kidney cells, intracytoplasmic virus was demonstrated by indirect immunofluorescence with convalescent serum from the patient.


Response to “Novel Middle East respiratory syndrome coronavirus”


title: Pathogen–Host Defense in the Evolution of Depression: Insights into Epidemiology, Genetics, Bioregional Differences and Female Preponderance

text: Significant attention has been paid to the potential adaptive value of depression as it relates to interactions with people in the social world. However, in this review, we outline the rationale of why certain features of depression including its environmental and genetic risk factors, its association with the acute phase response and its age of onset and female preponderance appear to have evolved from human interactions with pathogens in the microbial world. Approaching the relationship between inflammation and depression from this evolutionary perspective yields a number of insights that may reveal important clues regarding the origin and epidemiology of the disorder as well as the persistence of its risk alleles in the modern human genome.


title: COVID-19 pneumonia with hemoptysis: Acute segmental pulmonary emboli associated with novel coronavirus infection

text: Abstract Recent retrospective studies from Wuhan, China suggest Novel Coronavirus Disease 2019 (COVID-19) may be associated with a hypercoagulable state and increased risk for venous thromboembolism. The overlap in the signs and symptoms of COVID-19 associated Acute Respiratory Distress Syndrome (ARDS) and COVID-19 with concurrent pulmonary embolism creates a diagnostic challenge for emergency medicine physicians in patients already at risk for renal impairment. However, identifying features atypical for COVID-19 alone may play a role in the judicious use of Computed Tomography Angiography among these patients. Hemoptysis is seen in roughly 13% of pulmonary embolism cases and infrequently reported among COVID-19 infections. Additionally, the presence of right heart strain on electrocardiography (EKG) is a well described clinical presentations of pulmonary embolism not reported commonly with COVID-19 infections.


title: Leveraging a Bayesian Network approach to model and analyze supplier vulnerability to severe weather risk: A case study of the U.S. pharmaceutical supply chain following Hurricane Maria

text: Abstract The United States government has identified the health care sector as part of the critical infrastructure for homeland security to protect citizens against health risks arising from terrorism, natural disasters, and epidemics. Citizens also have expectations about the role that health care plays in enjoying a good quality of life, by providing response systems to handle emergencies and other illness situations adequately. Among the systems required to support desired performance levels is a robust and resilient pharmaceutical supply chain that is free of disruption. Shortages of drugs place undue pressure on healthcare providers to devise alternative approaches to administer patient care. With climate change expected to result in increasingly severe weather patterns in the future, it is critical that logistics engineers understand the impact that a catastrophic weather event could have on supply chain disruption to facilitate the design of supply systems that are robust and resilient. This study investigates the main causal and intermediate events that led to risk propagation in, and disruption of, the U.S. pharmaceutical supply chain following Hurricane Maria. A causality Bayesian model is developed to depict linkages between risk events and quantify the associated cumulative risk. The quantification is further examined through different advanced techniques such as predictive inference reasoning and sensitivity analysis. The general interpretation of these analyses suggests that port resilience is imperative to pharmaceutical supply chain performance in the case of Puerto Rico.


Elevated interleukin‐6, interleukin‐10 and neutrophil : lymphocyte ratio as identifiers of severe coronavirus disease 2019


title: Early characteristics of the COVID-19 outbreak predict the subsequent epidemic size

text: OBJECTIVES: The largely resolved first wave of the COVID-19 epidemic in China provides a unique opportunity to investigate how the early characteristics of the COVID-19 outbreak predicts its subsequent size. METHODS: We collected publicly available COVID-19 epidemiological data from 436 Chinese cities during 16(th) January-15(th) March 2020. Based on 45 cities which reported >100 confirmed cases, we examined the correlation between early-stage epidemic characteristics and subsequent epidemic size. RESULTS: We identified a transition point from a slow- to a fast-growing phase for COVID-19 at 5.5 (95% CI, 4.6-6.4) days after the first report, and 30 confirmed cases marked a critical threshold for this transition. The average time for the number of confirmed cases to increase from 30 to 100 (time from 30-to-100) was 6.6 (5.3-7.9) days, and the average case-fatality rate in the first 100 confirmed cases (CFR-100) was 0.8% (0.2-1.4%). The subsequent epidemic size per million population was significantly associated with both of these indicators. We predict a ranking of epidemic size in the cities based on these two indicators and found it highly correlated with the actual ranking of epidemic size. CONCLUSIONS: Early epidemic characteristics are important indicators for the size of the entire epidemic.


title: Accessibility of a critical prion protein region involved in strain recognition and its implications for the early detection of prions

text: Human prion diseases are characterized by the accumulation in the brain of proteinase K (PK)-resistant prion protein designated PrP27-30 detectable by the 3F4 antibody against human PrP109-112. We recently identified a new PK-resistant PrP species, designated PrP(*20), in uninfected human and animal brains. It was preferentially detected with the 1E4 antibody against human PrP 97-108 but not with the anti-PrP 3F4 antibody, although the 3F4 epitope is adjacent to the 1E4 epitope in the PrP(*20) molecule. The present study reveals that removal of the N-terminal amino acids up to residue 91 significantly increases accessibility of the 1E4 antibody to PrP of brains and cultured cells. In contrast to cells expressing wild-type PrP, cells expressing pathogenic mutant PrP accumulate not only PrP(*20) but also a small amount of 3F4-detected PK-resistant PrP27-30. Remarkably, during the course of human prion disease, a transition from an increase in 1E4-detected PrP(*20) to the occurrence of the 3F4-detected PrP27-30 was observed. Our study suggests that an increase in the level of PrP(*20) characterizes the early stages of prion diseases.


Laboratory Medicine: Meeting the Needs of Mediterranean Nations


title: Effect of Multi-Microbial Probiotic Formulation Bokashi on Pro- and Anti-Inflammatory Cytokines Profile in the Serum, Colostrum and Milk of Sows, and in a Culture of Polymorphonuclear Cells Isolated from Colostrum

text: The use of probiotics in sows during pregnancy and lactation and their impact on the quality of colostrum and milk, as well as the health conditions of their offspring during the rearing period, are currently gaining the attention of researchers. The aim of the study was to determine the effect of Bokashi formulation on the concentrations of pro- and anti-inflammatory cytokines in the serum of sows during pregnancy, in their colostrum and milk, and in a culture of Con-A-stimulated polymorphonuclear cells (PMNs) isolated from the colostrum. The study was conducted on 60 sows aged 2–4 years. EM Bokashi were added to the sows’ feed. The material for the study consisted of peripheral blood, colostrum, and milk. Blood samples were collected from the sows on days 60 and 114 of gestation. Colostrum and milk samples were collected from all sows at 0, 24, 48, 72, 96, 120, 144, and 168 h after parturition. The results indicate that the use of Bokashi as feed additives resulted in increased concentrations of pro-inflammatory cytokines TNF-α and IL-6, which increase the protective capacity of the colostrum by stimulating cellular immune mechanisms protecting the sow and neonates against infection. At the same time, the increased concentrations of cytokines IL-4, IL-10, TGF-β, and of immunoglobulins in the colostrum and milk from sows in the experimental group demonstrate the immunoregulatory effect of Bokashi on Th2 cells and may lead to increased expression of regulatory T cells and polarization of the immune response from Th1 to Th2.


title: Psychosocial consequences of infectious diseases

text: Abstract Historically, there has been an exaggerated fear related to infection compared to other conditions. Infection possesses unique characteristics that account for this disproportionate degree of fear: it is transmitted rapidly and invisibly; historically, it has accounted for major morbidity and mortality; old forms re-emerge and new forms emerge; and both the media and society are often in awe. Because, in an outbreak, the patient is both a victim and a vector, and because there exists the potential for infringement of personal rights in order to control an outbreak, infection may be viewed (and has been depicted in popular culture) as a foreign invasion. During recent outbreaks, fear, denial, stigmatization and loss have been recorded in the implicated individuals. Stigmatization and discrimination may further involve ethical correlations, and attempts to adress these issues through activism may also have unwarranted effects. Public health initiatives can address the public's fears by increasing health literacy, which can contribute to reducing stigmatization.


title: Kunjin replicon-based simian immunodeficiency virus gag vaccines

text: Abstract An RNA-based, non-cytopathic replicon vector system, based on the flavivirus Kunjin, has shown considerable promise as a new vaccine delivery system. Here we describe the testing in mice of four different SIVmac239 gag vaccines delivered by Kunjin replicon virus-like-particles. The four vaccines encoded the wild type gag gene, an RNA-optimised gag gene, a codon-optimised gag gene and a modified gag-pol gene construct. The vaccines behaved quite differently for induction of effector memory and central memory responses, for mediation of protection, and with respect to insert stability, with the SIV gag-pol vaccine providing the optimal performance. These results illustrate that for an RNA-based vector the RNA sequence of the antigen can have profound and unforeseen consequences on vaccine behaviour.


title: Helmet Modification to PPE with 3D Printing During the COVID-19 Pandemic at Duke University Medical Center: A Novel Technique

text: Abstract Care for patients during COVID-19 poses challenges that require the protection of staff with recommendations that health care workers wear at minimum, an N95 mask or equivalent while performing an aerosol-generating procedure with a face shield. The United States faces shortages of personal protective equipment, and surgeons who use loupes and headlights have difficulty using these in conjunction with face shields. Most arthroplasty surgeons use surgical helmet systems, but in the current pandemic, many hospitals have delayed elective arthroplasty surgeries and the helmet systems are going unused. As a result, the authors have begun retrofitting these arthroplasty helmets to serve as personal protective equipment (PPE). The purpose of this paper is to outline the conception, design, donning technique, and safety testing of these arthroplasty helmets being re-purposed as PPE.


title: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges

text: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; previously provisionally named 2019 novel coronavirus or 2019-nCoV) disease (COVID-19) in China at the end of 2019 has caused a large global outbreak and is a major public health issue. As of 11 February 2020, data from the World Health Organization (WHO) have shown that more than 43 000 confirmed cases have been identified in 28 countries/regions, with >99% of cases being detected in China. On 30 January 2020, the WHO declared COVID-19 as the sixth public health emergency of international concern. SARS-CoV-2 is closely related to two bat-derived severe acute respiratory syndrome-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21. It is spread by human-to-human transmission via droplets or direct contact, and infection has been estimated to have mean incubation period of 6.4 days and a basic reproduction number of 2.24–3.58. Among patients with pneumonia caused by SARS-CoV-2 (novel coronavirus pneumonia or Wuhan pneumonia), fever was the most common symptom, followed by cough. Bilateral lung involvement with ground-glass opacity was the most common finding from computed tomography images of the chest. The one case of SARS-CoV-2 pneumonia in the USA is responding well to remdesivir, which is now undergoing a clinical trial in China. Currently, controlling infection to prevent the spread of SARS-CoV-2 is the primary intervention being used. However, public health authorities should keep monitoring the situation closely, as the more we can learn about this novel virus and its associated outbreak, the better we can respond.


title: Management of Gynecology Patients during COVID-19 Pandemic: Chinese Expert Consensus

text: Abstract: Since December 2019, the outbreak of novel coronavirus disease 2019 (COVID-19) became a major epidemic threat in China and later spread worldwide. During the COVID-19 outbreak in mainland China, the Chinese Obstetricians and Gynecologists Association (COGA) distributed guidelines regarding care of gynecologic patients. These guidelines were developed by the Obstetrics and Gynecology department at Peking Union Medical College Hospital (PUMCH) and represent an effort to integrate infection control strategy and promote professionalism in medical practice. The guidelines represent collaboration with experts from 31 provinces and autonomous regions of mainland China over 2 weeks' time. With the implementation of these guidelines no nosocomial infections of COVID-19 have been identified at PUMCH. We think these guidelines might be helpful to departments of obstetrics and gynecology internationally during these unprecedented times. In our guidelines, we describe basic infection precaution principles, an epidemiologic screening tool, prioritization of surgical procedures, and operating room requirements. Using these principles, we then review management of gynecologic patients during the COVID-19 epidemic in the outpatient and operative and non-operative inpatient settings, as well as in clinical trials.


title: Back to Normal: An Old Physics Route to Reduce SARS-CoV-2 Transmission in Indoor Spaces

text: [Image: see text] We advocate the widespread use of UV-C light as a short-term, easily deployable, and affordable way to limit virus spread in the current SARS-CoV-2 pandemic. Radical social distancing with the associated shutdown of schools, restaurants, sport clubs, workplaces, and traveling has been shown to be effective in reducing virus spread, but its economic and social costs are unsustainable in the medium term. Simple measures like frequent handwashing, facial masks, and other physical barriers are being commonly adopted to prevent virus transmission. However, their efficacy may be limited, particularly in shared indoor spaces, where, in addition to airborne transmission, elements with small surface areas such as elevator buttons, door handles, and handrails are frequently used and can also mediate transmission. We argue that additional measures are necessary to reduce virus transmission when people resume attending schools and jobs that require proximity or some degree of physical contact. Among the available alternatives, UV-C light satisfies the requirements of rapid, widespread, and economically viable deployment. Its implementation is only limited by current production capacities, an increase of which requires swift intervention by industry and authorities.


CoViD-19, confinement et accidents de la vie domestique chez l’enfant


title: Short Communication An epidemiological model for SARS-CoV-2

text: Abstract The spread of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is here investigated from an epidemic model considering four pathways of person-to-person transmission. These pathways represent the propagation of this novel coronavirus by asymptomatic and symptomatic infected individuals. In this work, analytical expressions for the disease-free and endemic steady-states are derived. Also, the conditions for eradication of this contagious disease are determined. By taking into account realistic parameter values, the proposed model shows an oscillatory convergence to the endemic steady-state, which means the occurrence of a sequence of peaks in the number of sick individuals as time passes. These results are discussed from a public health standpoint.


title: A Rapid and Specific Assay for the Detection of MERS-CoV

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel human coronavirus that can cause human respiratory disease. The development of a detection method for this virus that can lead to rapid and accurate diagnosis would be significant. In this study, we established a nucleic acid visualization technique that combines the reverse transcription loop-mediated isothermal amplification technique and a vertical flow visualization strip (RT-LAMP-VF) to detect the N gene of MERS-CoV. The RT-LAMP-VF assay was performed in a constant temperature water bath for 30 min, and the result was visible by the naked eye within 5 min. The RT-LAMP-VF assay was capable of detecting 2 × 10(1) copies/μl of synthesized RNA transcript and 1 × 10(1) copies/μl of MERS-CoV RNA. The method exhibits no cross-reactivities with multiple CoVs including SARS-related (SARSr)-CoV, HKU4, HKU1, OC43 and 229E, and thus exhibits high specificity. Compared to the real-time RT-PCR (rRT-PCR) method recommended by the World Health Organization (WHO), the RT-LAMP-VF assay is easy to handle, does not require expensive equipment and can rapidly complete detection within 35 min.


title: Detection of 12 respiratory viruses by duplex real time PCR assays in respiratory samples

text: Abstract Different viruses can be responsible for similar clinical manifestations of respiratory infections. Thus, the etiological diagnosis of respiratory viral diseases requires the detection of a large number of viruses. In this study, 6 duplex real-time PCR assays, using EvaGreen intercalating dye, were developed to detect 12 major viruses responsible for respiratory diseases: influenza A and B viruses, enteroviruses (including enterovirus spp, and rhinovirus spp), respiratory syncytial virus, human metapneumovirus, coronaviruses group I (of which CoV 229E and CoV NL63 are part) and II (including CoV OC43 and CoV HKU1), parainfluenza viruses type 1, 2, 3 and 4, human adenoviruses and human bocaviruses. The 2 target viruses of each duplex reaction were distinguishable by the melting temperatures of their amplicons. The 6 duplex real time PCR assays were applied for diagnostic purpose on 202 respiratory samples from 157 patients. One hundred fifty-seven samples were throat swabs and 45 were bronchoalveolar lavages. The results of the duplex PCR assays were confirmed by comparison with a commercial, validated, assay; in addition, the positive results were confirmed by sequencing. The analytical sensitivity of the duplex PCR assays varied from 103 copies/ml to 104 copies/ml. For parainfluenza virus 2 only it was 105 copies/ml. Seventy clinical samples (35%) from 55 patients (30 children and 25 adults) were positive for 1 or more viruses. In adult patients, influenza A virus was the most frequently detected respiratory virus followed by rhinoviruses. In contrast, respiratory syncytial virus was the most common virus in children, followed by enteroviruses, influenza A virus and coronavirus NL63. The small number of samples/patients does not allow us to draw any epidemiological conclusion. Altogether, the results of this study indicate that the 6 duplex PCR assays described in this study are sensitive, specific and cost-effective. Thus, this assay could be particularly useful to identify the main respiratory viruses directly from clinical samples, after nucleic acid extraction, and, also, to screen a large number of patients for epidemiological studies.


title: A protocol for a systematic literature review: comparing the impact of seasonal and meteorological parameters on acute respiratory infections in Indigenous and non-Indigenous peoples

text: BACKGROUND: Acute respiratory infections (ARI) are a leading cause of morbidity and mortality globally, and are often linked to seasonal and/or meteorological conditions. Globally, Indigenous peoples may experience a different burden of ARI compared to non-Indigenous peoples. This protocol outlines our process for conducting a systematic review to investigate whether associations between ARI and seasonal or meteorological parameters differ between Indigenous and non-Indigenous groups residing in the same geographical region. METHODOLOGY: A search string will be used to search PubMed(®), CAB Abstracts/CAB Direct(©), and Science Citation Index(®) aggregator databases. Articles will be screened using inclusion/exclusion criteria applied first at the title and abstract level, and then at the full article level by two independent reviewers. Articles maintained after full article screening will undergo risk of bias assessment and data will be extracted. Heterogeneity tests, meta-analysis, and forest and funnel plots will be used to synthesize the results of eligible studies. DISCUSSION AND REGISTRATION: This protocol paper describes our systematic review methods to identify and analyze relevant ARI, season, and meteorological literature with robust reporting. The results are intended to improve our understanding of potential associations between seasonal and meteorological parameters and ARI and, if identified, whether this association varies by place, population, or other characteristics. The protocol is registered in the PROSPERO database (#38051). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13643-016-0399-x) contains supplementary material, which is available to authorized users.


An authority for crisis coordination and accountability


title: Coronaviruses and SARS-CoV-2: A Brief Overview

text: In late December 2019, several cases of pneumonia of unknown origin were reported from China, which in early January 2020 were announced to be caused by a novel coronavirus. The virus was later denominated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and defined as the causal agent of Coronavirus Disease 2019 (COVID-19). Despite massive attempts to contain the disease in China, the virus has spread globally, and COVID-19 was declared a pandemic by the World Health Organization (WHO) in March 2020. Here we provide a short background on coronaviruses, and describe in more detail the novel SARS-CoV-2 and attempts to identify effective therapies against COVID-19.


title: A review of studies on animal reservoirs of the SARS coronavirus

text: Abstract In this review, we summarize the researches on animal reservoirs of the SARS coronavirus (SARS-CoV). Masked palm civets were suspected as the origin of the SARS outbreak in 2003 and was confirmed as the direct origin of SARS cases with mild symptom in 2004. Sequence analysis of the SARS-CoV-like virus in masked palm civets indicated that they were highly homologous to human SARS-CoV with nt identity over 99.6%, indicating the virus has not been circulating in the population of masked palm civets for a very long time. Alignment of 10 complete viral genome sequences from masked palm civets with those of human SARS-CoVs revealed 26 conserved single-nucleotide variations (SNVs) in the viruses from masked palm civets. These conserved SNVs were gradually lost from the genomes of viruses isolated from the early phase to late phase human patients of the 2003 SARS epidemic. In 2005, horseshoe bats were identified as the natural reservoir of a group of coronaviruses that are distantly related to SARS-CoV. The genome sequences of bat SARS-like coronavirus had about 88–92% nt identity with that of the SARS-CoV. The prevalence of antibodies and viral RNA in different bat species and the characteristics of the bat SARS-like coronavirus were elucidated. Apart from masked palm civets and bats, 29 other animal species had been tested for the SARS-CoV, and the results are summarized in this paper.


title: Using LongSAGE to Detect Biomarkers of Cervical Cancer Potentially Amenable to Optical Contrast Agent Labelling

text: Sixteen longSAGE libraries from four different clinical stages of cervical intraepithelial neoplasia have enabled us to identify novel cell-surface biomarkers indicative of CIN stage. By comparing gene expression profiles of cervical tissue at early and advanced stages of CIN, several genes are identified to be novel genetic markers. We present fifty-six cell-surface gene products differentially expressed during progression of CIN. These cell surface proteins are being examined to establish their capacity for optical contrast agent binding. Contrast agent visualization will allow real-time assessment of the physiological state of the disease process bringing vast benefit to cancer care. The data discussed in this publication have been submitted to NCBIs Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/) and are accessible through GEO Series accession number GSE6252.


title: Identification and genetic characterization of porcine hemagglutinating encephalomyelitis virus from domestic piglets in China

text: In this study, we investigated an acute outbreak of porcine hemagglutinating encephalomyelitis on a farm of 127 pigs in Jilin province, China. Porcine hemagglutinating encephalomyelitis virus (PHEV) was detected in suckling and weaning pigs by RT-PCR assays. Coronavirus-like particles were observed by electron microscopy. The virus isolate was designated PHEV-JT06. The clinical signs, nervous symptoms and positive labeling of neurons in the cerebral cortex with an immunohistochemical stain in PHEV-JT06-infected BALB/c mice supported the diagnosis of PHEV infection. The five full-length PHEV-JT06 structural genes were cloned, sequenced and analyzed. Phylogenetic studies based on the nucleotide and amino acid sequences of the five genes in the outbreak showed that PHEV remained genetically stable. PHEV shares 95.3-99.3 % amino acid sequence identity with American strains (AY078417), suggesting that the Chinese isolate is most likely derived from the North American strain. Additionally, PHEV, HCoV-OC43 and BCoV were genetically close. These results may provide some insights into the genotype of the etiological agent responsible for the porcine hemagglutinating encephalomyelitis outbreak and could also provide a comparative view of the genomics of the five structural proteins of PHEV.


title: Review: Viral infections and mechanisms of thrombosis and bleeding

text: Viral infections are associated with coagulation disorders. All aspects of the coagulation cascade, primary hemostasis, coagulation, and fibrinolysis, can be affected. As a consequence, thrombosis and disseminated intravascular coagulation, hemorrhage, or both, may occur. Investigation of coagulation disorders as a consequence of different viral infections have not been performed uniformly. Common pathways are therefore not fully elucidated. In many severe viral infections there is no treatment other than supportive measures. A better understanding of the pathophysiology behind the association of viral infections and coagulation disorders is crucial for developing therapeutic strategies. This is of special importance in case of severe complications, such as those seen in hemorrhagic viral infections, the incidence of which is increasing worldwide. To date, only a few promising targets have been discovered, meaning the implementation in a clinical context is still hampered. This review discusses non‐hemorrhagic and hemorrhagic viruses for which sufficient data on the association with hemostasis and related clinical features is available. This will enable clinicians to interpret research data and place them into a perspective. J. Med. Virol. 84:1680–1696, 2012. © 2012 Wiley Periodicals, Inc.


title: The weak cat. Practical approach and common neurological differentials

text: Practical relevance Weakness is recognized somewhat infrequently in cats, but is an important manifestation of neurological disease. The clinician must perform a complete neurological examination to determine the neuroanatomic basis for the weakness. As for all species, the neuroanatomic diagnosis allows the clinician to generate an appropriate differential diagnosis, to design a diagnostic plan, to prognosticate, and ultimately to develop a treatment plan. Clinical challenges The cause(s) of neurological weakness in the cat may be difficult to determine without access to advanced imaging modalities, cerebrospinal fluid analysis or electrodiagnostics. However, an accurate neuroanatomic diagnosis allows the clinician to pursue preliminary anomalous (vertebral anomalies), metabolic (eg, diabetes mellitus, electrolyte abnormalities) and neoplastic differentials via blood work, vertebral column and thoracic radiography, and abdominal ultrasound. Subsequently, referral to a specialty veterinary hospital may be warranted to pursue advanced neurodiagnostics. Audience This review provides a framework for generating a neuroanatomic and differential diagnosis in the weak cat. It also discusses the pathogenesis and clinical signs associated with the most common neurological differentials for feline paresis. As such, it is aimed at both primary health care and specialty veterinarians. Patient group The neurological conditions discussed in this review cause weakness in cats of all age groups.


Malaria kills more than Ebola virus disease


title: Analysis of multimerization of the SARS coronavirus nucleocapsid protein

text: Abstract Severe Acute Respiratory Syndrome (SARS), an emerging disease characterized by atypical pneumonia, has recently been attributed to a novel coronavirus. The genome of SARS Coronavirus (SARS-CoV) has recently been sequenced, and a number of genes identified, including that of the nucleocapsid protein (N). It is noted, however, that the N protein of SARS-CoV (SARS-CoV N) shares little homology with nucleocapsid proteins of other members of the coronavirus family [Science 300 (2003) 1399; Science 300 (2003) 1394]. N proteins of other coronavirus have been reported to be involved in forming the viral core and also in the packaging and transcription of the viral RNA. As data generated from some viral systems other than coronaviruses suggested that viral N–N self-interactions may be necessary for subsequent formation of the nucleocapsid and assembly of the viral particles, we decided to investigate SARS-CoV N–N interaction. By using mammalian two-hybrid system and sucrose gradient fractionations, a homotypic interaction of N, but not M, was detected by the two-hybrid analysis. The mammalian two-hybrid assay revealed an approximately 50-fold increase in SEAP activity (measurement of protein–protein interaction) in N–N interaction compared to that observed in either M–M or mock transfection. Furthermore, mutational analyses characterized that a serine/arginine-rich motif (SSRSSSRSRGNSR) between amino acids 184 and 196 is crucial for N protein oligomerization, since deletion of this region completely abolished the N protein self-multimerization. Finally, the full-length nucleocapsid protein expressed and purified from baculovirus system was found to form different levels of higher order structures as detected by Western blot analysis of the fractionated proteins. Collectively, these results may aid us in elucidating the mechanism pertaining to formation of viral nucleocapsid core, and designing molecular approaches to intervene SARS-CoV replication.


Teaching anatomy with dissection in the time of COVID‐19 is essential and possible


title: Ghosts of infections past: using archival samples to understand a century of monkeypox virus prevalence among host communities across space and time

text: Infectious diseases that originate from multiple wildlife hosts can be complex and problematic to manage. A full understanding is further limited by large temporal and spatial gaps in sampling. However, these limitations can be overcome, in part, by using historical samples, such as those derived from museum collections. Here, we screened over 1000 museum specimens collected over the past 120 years to examine the historical distribution and prevalence of monkeypox virus (MPXV) in five species of African rope squirrel (Funisciurus sp.) collected across Central Africa. We found evidence of MPXV infections in host species as early as 1899, half a century earlier than the first recognized case of MPXV in 1958, supporting the suggestion that historic pox-like outbreaks in humans and non-human primates may have been caused by MPXV rather than smallpox as originally thought. MPX viral DNA was found in 93 of 1038 (9.0%) specimens from five Funisciurus species (F. anerythrus, F. carruthersi, F. congicus, F. lemniscatus and F. pyrropus), of which F. carruthersi and pyrropus had not previously been identified as potential MPXV hosts. We additionally documented relative prevalence rates of infection in museum specimens of Funisciurus and examined the spatial and temporal distribution of MPXV in these potential host species across nearly a hundred years (1899–1993).


title: A Two-hybrid Screen Identifies Cathepsins B and L as Uncoating Factors for Adeno-associated Virus 2 and 8

text: Vectors based on different serotypes of adeno-associated virus hold great promise for human gene therapy, based on their unique tissue tropisms and distinct immunological profiles. A particularly interesting candidate is AAV8, which can efficiently and rapidly transduce a wide range of tissues in vivo. To further unravel the mechanisms behind AAV8 transduction, we used yeast two-hybrid analyses to screen a mouse liver complementary DNA library for cellular proteins capable of interacting with the viral capsid proteins. In total, we recovered approximately 700 clones, comprising over 300 independent genes. Sequence analyses revealed multiple hits for over 100 genes, including two encoding the endosomal cysteine proteases cathepsins B and L. Notably, these two proteases also physically interacted with the corresponding portion of the AAV2 capsid in yeast, but not with AAV5. We demonstrate that cathepsins B and L are essential for efficient AAV2- and AAV8-mediated transduction of mammalian cells, and document the ability of purified cathepsin B and L proteins to bind and cleave intact AAV2 and AAV8 particles in vitro. These data suggest that cathepsin-mediated cleavage could prime AAV capsids for subsequent nuclear uncoating, and indicate that analysis of additional genes recovered in our screen may help to further elucidate the mechanisms behind transduction by AAV8 and related serotypes.


title: Hepatitis C virus modelled as an indirectly transmitted infection highlights the centrality of injection drug equipment in disease dynamics

text: The hepatitis C virus (HCV) epidemic often occurs through the persistence of injection drug use. Mathematical models have been useful in understanding various aspects of the HCV epidemic, and especially, the importance of new treatment measures. Until now, however, few models have attempted to understand HCV in terms of an interaction between the various actors in an HCV outbreak—hosts, viruses and the needle injection equipment. In this study, we apply perspectives from the ecology of infectious diseases to model the transmission of HCV among a population of injection drug users. The products of our model suggest that modelling HCV as an indirectly transmitted infection—where the injection equipment serves as an environmental reservoir for infection—facilitates a more nuanced understanding of disease dynamics, by animating the underappreciated actors and interactions that frame disease. This lens may allow us to understand how certain public health interventions (e.g. needle exchange programmes) influence HCV epidemics. Lastly, we argue that this model is of particular importance in the light of the modern opioid epidemic, which has already been associated with outbreaks of viral diseases.


title: Mobile technology adoption across the lifespan: A mixed methods investigation to clarify adoption stages, and the influence of diffusion attributes

text: We conducted a multi-study, mixed-methods, longitudinal investigation to examine how mobile technology diffuses across the lifespan, in real time, within a multi-generational population, while seeking local knowledge through community-based participatory research. Using qualitative methods (QUAL), we examined technology adoption within and across three iterations (16 weeks) of a nine-wave longitudinal community technology-training workshop, situated within a 15-wave study. In parallel, we interrogated existing conceptualization and operationalization of diffusion of technology variables, then deductively evaluated the dominant DOI-related variables re-conceptualized through the community study in a large cross-sectional quantitative (QUAN) investigation. We interpreted our results consistently and iteratively with a mixed-methods approach that included conceptualization, operationalization, and empirical testing. We discovered that oft-conflated concepts of knowledge, use, and ownership represent distinct stages of adoption. Our findings suggest constant feedback/permeable boundaries between these stages, and that DOI attributes may influence mobile technology adoption stages differentially. We suggest that innovators seeking to facilitate mobile technology adoption should focus on reducing complexity, and establishing calibration of complexity perceptions. We propose a lifespan mobile technology diffusion model, and call to question the language used in investigations related to the digital divide. We strive to clarify labels that may stereotype vulnerable populations, such as older adults. Our research contributes to theories of technology adoption – particularly after the introduction of digital communication - the diffusion of innovations in the community over time, and technology adoption process as affected by interpersonal communication and relationships, including among the technologically undercapitalized and the digitally privileged.


title: Emergencies and Critical Care of Commonly Kept Fowl

text: Fowl are birds belonging to one of the 2 biological orders, the game fowl or land fowl (Galliformes) and the waterfowl (Anseriformes). Studies of anatomic and molecular similarities suggest these two groups are close evolutionary relatives. Multiple fowl species have a long history of domestication. Fowl are considered food-producing animals in most countries and clinicians should follow legislation regarding reportable diseases and antibiotic use, even if they are pets. This article reviews aspects of emergency care for most commonly kept fowl, including triage, patient assessment, diagnostic procedures, supportive care, short-term hospitalization, and common emergency presentations.


title: Loop-mediated isothermal amplification assay for the diagnosis of retinitis caused by herpes simplex virus-1

text: Abstract A loop-mediated isothermal amplification (LAMP) assay was developed for the detection of herpes simplex virus 1 (HSV-1). The specificity of the assay was tested using DNA extracted from HSV-1-infected rabbit corneal epithelium cultures, HSV-2 grown on Vero cell line, cytomegalovirus (CMV) (AD-169), varicella zoster virus (VZV) (Oka-vaccine), adenovirus, Aspergillus flavus and Staphylococcus aureus. The specificity of LAMP was confirmed by bidirectional sequencing of the amplicons. The sensitivity of the LAMP assay was tested using different concentrations of HSV-1 DNA. To evaluate the application of the LAMP assay in clinical diagnosis, we tested vitreous samples from 20 patients with suspected viral retinitis using LAMP and real-time PCR for HSV-1. The LAMP primers amplified only HSV-1 DNA; no LAMP products were detected with the DNAs of HSV-2, CMV, VZV, adenovirus A. flavus and S. aureus. The sequences of the positive HSV-1 LAMP products perfectly (99–100%) matched the HSV-1 sequences deposited in the GenBank database. LAMP is as sensitive as real-time PCR, with the lowest detection limit being 10 copies/μL of HSV-1 DNA. Of the 20 patients with suspected viral retinitis, four tested positive for HSV-1 using real- time PCR and LAMP. A 100% concordance was observed across the two methods. The LAMP assay is a rapid, highly specific and sensitive method for the diagnosis of retinitis caused by HSV-1.


title: Evaluation of a programme for ‘Rapid Assessment of Febrile Travelers’ (RAFT): a clinic-based quality improvement initiative

text: BACKGROUND: Fever in the returned traveller is a potential medical emergency warranting prompt attention to exclude life-threatening illnesses. However, prolonged evaluation in the emergency department (ED) may not be required for all patients. As a quality improvement initiative, we implemented an algorithm for rapid assessment of febrile travelers (RAFT) in an ambulatory setting. METHODS: Criteria for RAFT referral include: presentation to the ED, reported fever and travel to the tropics or subtropics within the past year. Exclusion criteria include Plasmodium falciparum malaria, and fulfilment of admission criteria such as unstable vital signs or significant laboratory derangements. We performed a time series analysis preimplementation and postimplementation, with primary outcome of wait time to tropical medicine consultation. Secondary outcomes included number of ED visits averted for repeat malaria testing, and algorithm adherence. RESULTS: From February 2014 to December 2015, 154 patients were seen in the RAFT clinic: 68 men and 86 women. Median age was 36 years (range 16–78 years). Mean time to RAFT clinic assessment was 1.2±0.07 days (range 0–4 days) postimplementation, compared to 5.4±1.8 days (range 0–26 days) prior to implementation (p<0.0001). The RAFT clinic averted 132 repeat malaria screens in the ED over the study period (average 6 per month). Common diagnoses were: traveller's diarrhoea (n=27, 17.5%), dengue (n=12, 8%), viral upper respiratory tract infection (n=11, 7%), chikungunya (n=10, 6.5%), laboratory-confirmed influenza (n=8, 5%) and lobar pneumonia (n=8, 5%). CONCLUSIONS: In addition to provision of more timely care to ambulatory febrile returned travellers, we reduced ED bed-usage by providing an alternate setting for follow-up malaria screening, and treatment of infectious diseases manageable in an outpatient setting, but requiring specific therapy.


Patients with MS treated with immunosuppressive agents: across the COVID-19 spectrum


title: Artificial Intelligence Distinguishes COVID-19 from Community Acquired Pneumonia on Chest CT

text: BACKGROUND: Coronavirus disease has widely spread all over the world since the beginning of 2020. It is desirable to develop automatic and accurate detection of COVID-19 using chest CT. PURPOSE: To develop a fully automatic framework to detect COVID-19 using chest CT and evaluate its performances. MATERIALS AND METHODS: In this retrospective and multi-center study, a deep learning model, COVID-19 detection neural network (COVNet), was developed to extract visual features from volumetric chest CT exams for the detection of COVID-19. Community acquired pneumonia (CAP) and other non-pneumonia CT exams were included to test the robustness of the model. The datasets were collected from 6 hospitals between August 2016 and February 2020. Diagnostic performance was assessed by the area under the receiver operating characteristic curve (AUC), sensitivity and specificity. RESULTS: The collected dataset consisted of 4356 chest CT exams from 3,322 patients. The average age is 49±15 years and there were slightly more male patients than female (1838 vs 1484; p-value=0.29). The per-exam sensitivity and specificity for detecting COVID-19 in the independent test set was 114 of 127 (90% [95% CI: 83%, 94%]) and 294 of 307 (96% [95% CI: 93%, 98%]), respectively, with an AUC of 0.96 (p-value<0.001). The per-exam sensitivity and specificity for detecting CAP in the independent test set was 87% (152 of 175) and 92% (239 of 259), respectively, with an AUC of 0.95 (95% CI: 0.93, 0.97). CONCLUSIONS: A deep learning model can accurately detect COVID-19 and differentiate it from community acquired pneumonia and other lung diseases.


title: Covid-19: Gorman-Rupp continues to operate in Ohio

text: The Gorman-Rupp Co will continue to operate all of its locations within the State of Ohio as an essential business during a state-wide Stay at Home Order issued in response to the Covid-19 outbreak.


title: Obvious and Hidden Anxiety and the Related Factors in Operating Room Nurses Employed in General Hospital, Qazvin, Iran: A Cross-Sectional Study

text: BACKGROUND: Health promotion and security of manpower in a society is one of the pillars to progress a society. Anxiety, is the most common psychological disorder in societies and occupations like nursing, anesthesia technicians and operation room technicians. The aim of this study was to investigate prevalence of anxiety, and its severity in Iranian nurses working in operation room. Also, we determined the most important associated factors with anxiety. METHODS: In this cross sectional study, 152 nurses working in operating room participated. The tool to gather the data was a questionnaire, that included three parts; demographic information, obvious anxiety questions and hidden anxiety questions of Spielburger. Obtained data was analysed with SPSS 16 software. RESULTS: The majority of participants were females (94.7%) with experience at work less than 10 years (84.9%). The average scores of participants in obvious and hidden anxiety were 41.9±39.4 (range 20 to 75) and 39.4±8.2 (range 20 to 70), respectively. Anxiety level was significantly higher in females than males (P=0.04). The most prevalent cause of anxiety, was contact with infected biological factors (23% of nurses). The less important cause was concern about retirement (42.8% of nurses). CONCLUSION: Our results suggest that, anxiety disorders is prevalent in Iranian nurses working in public city hospitals, which warrants immediate programs for intervention to improve working situations in work place.


title: Foldamers in Medicinal Chemistry

text: Bio-inspired synthetic backbones leading to foldamers can provide effective biopolymer mimics with new and improved properties in a physiological environment, and in turn could serve as useful tools to study biology and lead to practical applications in the areas of diagnostics or therapeutics. Remarkable progress has been accomplished over the past 20 years with the discovery of many potent bioactive foldamers originating from diverse backbones and targeting a whole spectrum of bio(macro)molecules such as membranes, protein surfaces, and nucleic acids. These current achievements, future opportunities, and key challenges that remain are discussed in this article.


title: Unknown unknowns – COVID-19 and potential global mortality

text: COVID-19 (SARS-CoV-2) is currently a global pandemic. This paper will attempt to estimate global infection rates and potential resultant mortality in the absence of effective treatment and/or vaccination. Calculations are based on World Health Organisation data from Wuhan in China: 14% of infected cases are severe, 5% require intensive care and 4% die. Estimated infection rates and mortality rates at the level of continents and some individual countries (when these are of sufficient size) are tabulated. This pandemic may cause close to half a billion deaths, i.e. 6% of the global population – and potentially more. At the risk of sounding sensational, but with a sober sense of realism, healthcare risks being plunged into the Middle-Ages if the public do not do their part. Infection cannot occur in the absence of contact. The only way to mitigate these numbers is to apply social distancing and take the standard precautions so frequently reiterated by Public Health: hand washing, avoid touching the face and so on. These measures are crucial as the human cost is going to be unthinkable even in the best-case scenarios that epidemiologists are modelling.


title: Why We (Probably) Must Deliberately Infect

text: In the grip of a pandemic of proportions that have not been seen for generations, some have proposed conducting “human challenge” vaccine trials in which healthy volunteers are deliberately infected with the SARS-CoV-2 virus that causes COVID-19. Such trials might substantially speed up the search for a safe and effective vaccine and save many thousands of lives. I argue that such trials are not only permissible, but given reasonable assumptions, they are morally required, subject to some important caveats.


title: Comparative immunological evaluation of recombinant Salmonella Typhimurium strains expressing model antigens as live oral vaccines

text: BACKGROUND: Despite the development of various systems to generate live recombinant Salmonella Typhimurium vaccine strains, little work has been performed to systematically evaluate and compare their relative immunogenicity. Such information would provide invaluable guidance for the future rational design of live recombinant Salmonella oral vaccines. RESULT: To compare vaccine strains encoded with different antigen delivery and expression strategies, a series of recombinant Salmonella Typhimurium strains were constructed that expressed either the enhanced green fluorescent protein (EGFP) or a fragment of the hemagglutinin (HA) protein from the H5N1 influenza virus, as model antigens. The antigens were expressed from the chromosome, from high or low-copy plasmids, or encoded on a eukaryotic expression plasmid. Antigens were targeted for expression in either the cytoplasm or the outer membrane. Combinations of strategies were employed to evaluate the efficacy of combined delivery/expression approaches. After investigating in vitro and in vivo antigen expression, growth and infection abilities; the immunogenicity of the constructed recombinant Salmonella strains was evaluated in mice. Using the soluble model antigen EGFP, our results indicated that vaccine strains with high and stable antigen expression exhibited high B cell responses, whilst eukaryotic expression or colonization with good construct stability was critical for T cell responses. For the insoluble model antigen HA, an outer membrane expression strategy induced better B cell and T cell responses than a cytoplasmic strategy. Most notably, the combination of two different expression strategies did not increase the immune response elicited. CONCLUSION: Through systematically evaluating and comparing the immunogenicity of the constructed recombinant Salmonella strains in mice, we identified their respective advantages and deleterious or synergistic effects. Different construction strategies were optimally-required for soluble versus insoluble forms of the protein antigens. If an antigen, such as EGFP, is soluble and expressed at high levels, a low-copy plasmid-cytoplasmic expression strategy is recommended; since it provokes the highest B cell responses and also induces good T cell responses. If a T cell response is preferred, a eukaryotic expression plasmid or a chromosome-based, cytoplasmic-expression strategy is more effective. For insoluble antigens such as HA, an outer membrane expression strategy is recommended.


title: Description and initial characterization of metatranscriptomic nidovirus-like genomes from the proposed new family Abyssoviridae, and from a sister group to the Coronavirinae, the proposed genus Alphaletovirus

text: Abstract Transcriptomics has the potential to discover new RNA virus genomes by sequencing total intracellular RNA pools. In this study, we have searched publicly available transcriptomes for sequences similar to viruses of the Nidovirales order. We report two potential nidovirus genomes, a highly divergent 35.9 kb likely complete genome from the California sea hare Aplysia californica, which we assign to a nidovirus named Aplysia abyssovirus 1 (AAbV), and a coronavirus-like 22.3 kb partial genome from the ornamented pygmy frog Microhyla fissipes, which we assign to a nidovirus named Microhyla alphaletovirus 1 (MLeV). AAbV was shown to encode a functional main proteinase, and a translational readthrough signal. Phylogenetic analysis suggested that AAbV represents a new family, proposed here as Abyssoviridae. MLeV represents a sister group to the other known coronaviruses. The importance of MLeV and AAbV for understanding nidovirus evolution, and the origin of terrestrial nidoviruses are discussed.


title: A chimeric multi-epitope DNA vaccine elicited specific antibody response against severe acute respiratory syndrome-associated coronavirus which attenuated the virulence of SARS-CoV in vitro

text: Abstract Epitope-based vaccines designed to induce antibody responses specific for severe acute respiratory syndrome-associated coronavirus (SARS-CoV) are being developed as a means for increasing vaccine potency. In this study, we identified four B cell epitopes from the spike (S) and membrane (M) protein through bioinformatics analysis and constructed a multi-epitope DNA vaccine. Intramuscular immunization of mice with this vaccine was sufficient to induce specific prime as well as a long-term memory humoral immune response to at least two candidate epitopes, S437–459 and M1–20. A DNA prime–protein boost strategy greatly enhanced the antibody generation and the immune sera not only reacted with the lysates of SARS-CoV-infected Vero cells but also neutralized the cytopathic effect of SARS by 75% at 1:160 dilution. The novel immunogenic S protein peptide revealed in this study provides new target for SARS vaccine design; and our work indicated multi-epitope DNA vaccine as an effective means for eliciting polyvalent humoral immune response against SARS-CoV.


title: Identification of Leukotoxin and other vaccine candidate proteins in a Mannheimia haemolytica commercial antigen

text: Bovine Respiratory Disease is the most costly disease that affects beef and dairy cattle industry. Its etiology is multifactorial, arising from predisposing environmental stress conditions as well as the action of several different respiratory pathogens. This situation has hindered the development of effective control strategies. Although different type of vaccines are available, many currently marketed vaccines are based on inactivated cultures of the main viral and bacterial agents involved in this pathology. The molecular composition of commercial veterinary vaccines is a critical issue. The present work aims to define at the proteomic level the most relevant valence of a line of commercial respiratory vaccines widely used in Central and South America. Since Mannheimia haemolytica is responsible for most of the disease associated morbid-mortality, we focused on the main proteins secreted by this pathogen, in particular Leukotoxin A, its main virulence factor. By Western blot analysis and mass spectrometry, Leukotoxin A was identified as a major component of M. haemolytica culture supernatants. We also identified other ten M. haemolytica proteins, including outer membrane proteins, periplasmic transmembrane solute transporters and iron binding proteins, which are relevant to achieve protective immunity against the pathogen. This work allowed a detailed molecular characterization of this vaccine component, providing evidence of its quality and efficacy. Furthermore, our results contributed to the identification of several proteins of interest as subunit vaccine candidates.


title: A University-Based Social Services Parent-Training Model: A Telehealth Adaptation During the COVID-19 Pandemic

text: With the COVID-19 pandemic resulting in social-distancing recommendations, many service providers find themselves altering the way they must provide medically necessary therapy. Even with the advent of more advanced telehealth technologies, the implementation of behavioral programming falls mainly on the caregivers of the clients that are served. This crisis brings to light ethical dilemmas and upends the current ways many programs may have been implemented across the world. As a result, a reevaluation of how these services are delivered is in order. This article reviews how a university-based, state-funded service delivery program (USSDP) provided essential and necessary services during the COVID-19 pandemic. Specifically, the purpose of this article is to describe how the USSDP quickly adopted a telehealth care model in a program that previously had not delivered services in this modality. Ethical, contextual, and competency-based factors are reviewed in the context of this organization, followed by a dialogue on broader generalization suggestions utilizing an active support model of care within telehealth restrictions.


title: NS3 protein of hepatitis C virus regulates cyclooxygenase-2 expression through multiple signaling pathways

text: Abstract Hepatitis C virus (HCV) causes chronic hepatitis, which often results in the development of liver cirrhosis and hepatocellular carcinoma (HCC) worldwide. In this study, we demonstrated that the non-structural protein NS3 of HCV enhances cyclooxygenase-2 (COX-2) gene promoter activity, COX-2 mRNA expression, COX-2 protein production, and prostaglandin E2 (PGE2) release in HepG2 cells in a concentration-dependent fashion. We also showed that transcription factor NF-κB is required for the activation of COX-2 regulated by NS3. In addition, multiple signaling pathways are involved cooperatively in the expression of COX-2 activated by the viral protein in a calcium-independent manner, which requires signaling components including JNK, ERK, and PKD2. A thorough investigation of mechanism involved in the activation of COX-2 regulated by HCV would provide insights into our understanding the processes of liver inflammatory response and hepatocellular carcinoma development caused by the viral infection and also into the development of novel therapeutics against HCV infection.


title: Kawasaki disease: 40 years after the original report

text: The cause of Kawasaki disease (KD) remains unknown, although a number of epidemiologic and clinical observations suggest it is triggered by one or more infectious agents, each of which can result in the clinical manifestation of the disease. Advances have been made in the management of the disease with the introduction of aspirin and intravenous immunoglobulin (IVIG), which have had a significant impact on lowering the rate of coronary artery aneurysms and death from the disease. Questions remain regarding the management of those patients who fail to respond to IVIG. It appears that some patients with severe KD who are resistant to IVIG may benefit from IV pulse steroid therapy or infliximab infusion. However, a recent multicenter, randomized, controlled trial did not support the addition of a pulsed dose of intravenous methylprednisolone to the conventional IVIG therapy for the primary treatment of KD. It remains to be seen whether other anti-inflammatory agents such as immunosuppressive therapies or new biologics will play a role in the management of patients with KD.


title: Hemoglobin Cleavage Site-Specificity of the Plasmodium falciparum Cysteine Proteases Falcipain-2 and Falcipain-3

text: The Plasmodium falciparum cysteine proteases falcipain-2 and falcipain-3 degrade host hemoglobin to provide free amino acids for parasite protein synthesis. Hemoglobin hydrolysis has been described as an ordered process initiated by aspartic proteases, but cysteine protease inhibitors completely block the process, suggesting that cysteine proteases can also initiate hemoglobin hydrolysis. To characterize the specific roles of falcipains, we used three approaches. First, using random P(1) – P(4) amino acid substrate libraries, falcipain-2 and falcipain-3 demonstrated strong preference for cleavage sites with Leu at the P(2) position. Second, with overlapping peptides spanning α and β globin and proteolysis-dependent (18)O labeling, hydrolysis was seen at many cleavage sites. Third, with intact hemoglobin, numerous cleavage products were identified. Our results suggest that hemoglobin hydrolysis by malaria parasites is not a highly ordered process, but rather proceeds with rapid cleavage by falcipains at multiple sites. However, falcipain-2 and falcipain-3 show strong specificity for P(2) Leu in small peptide substrates, in agreement with the specificity in optimized small molecule inhibitors that was identified previously. These results are consistent with a principal role of falcipain-2 and falcipain-3 in the hydrolysis of hemoglobin by P. falciparum and with the possibility of developing small molecule inhibitors with optimized specificity as antimalarial agents.


Neonatal necrotizing enterocolitis: a neonatal infection?


title: Transmissible Viral Vaccines

text: Genetic engineering now enables the design of live viral vaccines that are potentially transmissible. Some designs merely modify a single viral genome to improve on the age-old method of attenuation whereas other designs create chimeras of viral genomes. Transmission has the benefit of increasing herd immunity above that achieved by direct vaccination alone but also increases the opportunity for vaccine evolution, which typically undermines vaccine utility. Different designs have different epidemiological consequences but also experience different evolution. Approaches that integrate vaccine engineering with an understanding of evolution and epidemiology will reap the greatest benefit from vaccine transmission.


title: Middle East Respiratory Syndrome Coronavirus: A Case-Control Study of Hospitalized Patients

text: Background. There is a paucity of data regarding the differentiating characteristics of patients with laboratory-confirmed and those negative for Middle East respiratory syndrome coronavirus (MERS-CoV). Methods. This is a hospital-based case-control study comparing MERS-CoV–positive patients (cases) with MERS-CoV–negative controls. Results. A total of 17 case patients and 82 controls with a mean age of 60.7 years and 57 years, respectively (P = .553), were included. No statistical differences were observed in relation to sex, the presence of a fever or cough, and the presence of a single or multilobar infiltrate on chest radiography. The case patients were more likely to be overweight than the control group (mean body mass index, 32 vs 27.8; P = .035), to have diabetes mellitus (87% vs 47%; odds ratio [OR], 7.24; P = .015), and to have end-stage renal disease (33% vs 7%; OR, 7; P = .012). At the time of admission, tachypnea (27% vs 60%; OR, 0.24; P = .031) and respiratory distress (15% vs 51%; OR, 0.15; P = .012) were less frequent among case patients. MERS-CoV patients were more likely to have a normal white blood cell count than the control group (82% vs 52%; OR, 4.33; P = .029). Admission chest radiography with interstitial infiltrates was more frequent in case patients than in controls (67% vs 20%; OR, 8.13; P = .001). Case patients were more likely to be admitted to the intensive care unit (53% vs 20%; OR, 4.65; P = .025) and to have a high mortality rate (76% vs 15%; OR, 18.96; P < .001). Conclusions. Few clinical predictors could enhance the ability to predict which patients with pneumonia would have MERS-CoV. However, further prospective analysis and matched case-control studies may shed light on other predictors of infection.


title: Medical students’ knowledge, perceptions, and behavioral intentions towards the H1N1 influenza, swine flu, in Pakistan: A brief report

text: This study was conducted to assess the knowledge of H1N1 among medical students, their perceptions, and behavioral intentions in the wake of the H1N1 pandemic influenza. There were significant gaps in important self-isolation protocols and preventive measures. Increased contact with both patients and colleagues can lead to unintentional transmission and contraction of influenza. Universities should introduce and encourage infection control guidelines into routine curriculum.


title: Safety and Infectivity of Two Doses of Live -Attenuated Recombinant Cold-Passaged Human Parainfluenza Type 3 Virus Vaccine rHPIV3cp45 in HPIV3-Seronegative Young Children

text: BACKGROUND: Human parainfluenza virus type 3 (HPIV3) is a common cause of upper and lower respiratory tract illness in infants and young children. Live-attenuated cold-adapted HPIV3 vaccines have been evaluated in infants but a suitable interval for administration of a second dose of vaccine has not been defined. METHODS: HPIV3-seronegative children between the ages of 6 and 36 months were randomized 2:1 in a blinded study to receive two doses of 10(5) TCID(50) (50% tissue culture infectious dose) of live-attenuated, recombinant cold-passaged human PIV3 vaccine (rHPIV3cp45) or placebo 6 months apart. Serum antibody levels were assessed prior to and approximately 4-6 weeks after each dose. Vaccine virus infectivity, defined as detection of vaccine-HPIV3 in nasal wash and/or a ≥ 4-fold rise in serum antibody titer, and reactogenicity were assessed on days 3, 7, and 14 following immunization. RESULTS: Forty HPIV3-seronegative children (median age 13 months; range 6-35 months) were enrolled; 27 (68%) received vaccine and 13 (32%) received placebo. Infectivity was detected in 25 (96%) of 26 evaluable vaccinees following dose 1 and 9 of 26 subject (35%) following dose 2. Among those who shed virus, the median duration of viral shedding was 12 days (range, 6-15 days) after dose 1 and 6 days (range 3-8 days) after dose 2, with a mean peak log(10) viral titer of 3.4 PFU/mL (SD: 1.0) after dose 1 compared to1.5 PFU/mL (SD: 0.92) after dose 2. Overall, reactogenicity was mild, with no difference in rates of fever and upper respiratory infection symptoms between vaccine and placebo groups. CONCLUSION: rHPIV3cp45 was immunogenic and well-tolerated in seronegative young children. A second dose administered 6 months after the initial dose was restricted in those previously infected with vaccine virus; however, the second dose boosted antibody responses and induced antibody responses in two previously uninfected children.


title: Retrospective on the all-in-one retroviral nucleocapsid protein

text: Abstract This review aims at briefly presenting a retrospect on the retroviral nucleocapsid protein (NC), from an unspecific nucleic acid binding protein (NABP) to an all-in-one viral protein with multiple key functions in the early and late phases of the retrovirus replication cycle, notably reverse transcription of the genomic RNA and viral DNA integration into the host genome, and selection of the genomic RNA together with the initial steps of virus morphogenesis. In this context we will discuss the notion that NC protein has a flexible conformation and is thus a member of the growing family of intrinsically disordered proteins (IDPs) where disorder may account, at least in part, for its function as a nucleic acid (NA) chaperone and possibly as a protein chaperone vis-à-vis the viral DNA polymerase during reverse transcription. Lastly, we will briefly review the development of new anti-retroviral/AIDS compounds targeting HIV-1 NC because it represents an ideal target due to its multiple roles in the early and late phases of virus replication and its high degree of conservation.


title: Mechanisms of protective immune responses induced by the Plasmodium falciparum circumsporozoite protein-based, self-assembling protein nanoparticle vaccine

text: BACKGROUND: A lack of defined correlates of immunity for malaria, combined with the inability to induce long-lived sterile immune responses in a human host, demonstrate a need for improved understanding of potentially protective immune mechanisms for enhanced vaccine efficacy. Protective sterile immunity (>90%) against the Plasmodium falciparum circumsporozoite protein (CSP) has been achieved using a transgenically modified Plasmodium berghei sporozoite (Tg-Pb/PfCSP) and a self-assembling protein nanoparticle (SAPN) vaccine presenting CSP epitopes (PfCSP-SAPN). Here, several possible mechanisms involved in the independently protective humoral and cellular responses induced following SAPN immunization are described. METHODS: Inbred mice were vaccinated with PfCSP-SAPN in PBS. Serum antibodies were harvested and effects on P. falciparum sporozoites mobility and integrity were examined using phase contrast microscopy. The functionality of SAPN-induced antibodies on inhibition of sporozoite invasion and growth within primary human hepatocytes was also examined. The internal processing of SAPN by bone marrow-derived dendritic cells (BMDDC), using organelle-specific, fluorescent-tagged antibody or gold-encapsulated SAPN, was observed using confocal or electron microscopy, respectively. RESULTS: The results of this work demonstrate that PfCSP-SAPN induces epitope-specific antibody titers, predominantly of the Th2 isotype IgG1, and that serum antibodies from PfCSP-SAPN-immunized mice appear to target P. falciparum sporozoites via the classical pathway of complement. This results in sporozoite death as indicated by cessation of motility and the circumsporozoite precipitation reaction. Moreover, PfCSP-SAPN-induced antibodies are able to inhibit wild-type P. falciparum sporozoite invasion and growth within cultured primary human hepatocytes. In addition, the observation that PfCSP-SAPN are processed (and presented) to the immune system by dendritic cells in a slow and continuous fashion via transporter associated with antigen processing (TAP) recruitment to the early endosome (EE), and have partially delayed processing through the endoplasmic reticulum, has the potential to induce the long-lived, effector memory CD8(+) T-cells as described previously. CONCLUSION: This paper describes the examination of humoral and cellular immune mechanisms induced by PfCSP-SAPN vaccination which result in sterile host protection against a transgenic P. berghei malaria sporozoite expressing the P. falciparum CSP, and which significantly inhibits native P. falciparum sporozoites from invading and developing within cultured human hepatocytes. These results may indicate the type and mode of action of protective antibodies needed to control P. falciparum sporozoites from infecting humans as well as a potential mechanism of induction of protective long-lived effector memory CD8(+) T-cells.


title: The Rotavirus NSP4 Viroporin Domain is a Calcium-conducting Ion Channel

text: Viroporins are small virus-encoded ion channel proteins. Most viroporins are monovalent selective cation channels, with few showing the ability to conduct divalent cations, like calcium (Ca(2+)). Nevertheless, some viroporins are known to disrupt host cell Ca(2+) homeostasis, which is critical for virus replication and pathogenesis. Rotavirus nonstructural protein 4 (NSP4) is an endoplasmic reticulum transmembrane glycoprotein that has a viroporin domain (VPD), and NSP4 viroporin activity elevates cytosolic Ca(2+) in mammalian cells. The goal of this study was to demonstrate that the NSP4 VPD forms an ion channel and determine whether the channel can conduct Ca(2+). Using planar lipid bilayer and liposome patch clamp electrophysiology, we show that a synthetic peptide of the NSP4 VPD has ion channel activity. The NSP4 VPD was selective for cations over anions and channel activity was observed to have both well-defined “square top” openings as well as fast current fluctuations, similar to other viroporins. Importantly, the NSP4 VPD showed similar conductance of divalent cations (Ca(2+) and Ba(2+)) as monovalent cations (K(+)), but a viroporin defective mutant lacked Ca(2+) conductivity. These data demonstrate that the NSP4 VPD is a Ca(2+)-conducting viroporin and establish the mechanism by which NSP4 disturbs host cell Ca(2+) homeostasis.


Vulnerability, equity and universal coverage – a concept note


title: A genome-wide CRISPR screen identifies N-acetylglucosamine-1-phosphate transferase as a potential antiviral target for Ebola virus

text: There are no approved therapies for Ebola virus infection. Here, to find potential therapeutic targets, we perform a screen for genes essential for Ebola virus (EBOV) infection. We identify GNPTAB, which encodes the α and β subunits of N-acetylglucosamine-1-phosphate transferase. We show that EBOV infection of a GNPTAB knockout cell line is impaired, and that this is reversed by reconstituting GNPTAB expression. Fibroblasts from patients with mucolipidosis II, a disorder associated with mutations in GNPTAB, are refractory to EBOV, whereas cells from their healthy parents support infection. Impaired infection correlates with loss of the expression of cathepsin B, known to be essential for EBOV entry. GNPTAB activity is dependent upon proteolytic cleavage by the SKI-1/S1P protease. Inhibiting this protease with the small-molecule PF-429242 blocks EBOV entry and infection. Disruption of GNPTAB function may represent a strategy for a host-targeted therapy for EBOV.


Slums Are Not Places for Children to Live Vulnerabilities, Health Outcomes, and Possible Interventions


Inmunoglobulinas intravenosas: una alternativa terapéutica a tener en cuenta en el paciente trasplantado renal con COVID 19


title: Loop-mediated isothermal amplification for rapid detection and differentiation of wild-type pseudorabies and gene-deleted virus vaccines

text: Abstract A loop-mediated isothermal amplification (LAMP) assay was developed specifically for detection and differentiation of pseudorabies virus (PRV). One group of primers was designed to detect wild-type strains (i.e., strains with the gE gene) and the other group of primers was designed to detect both PRV gE-vaccine and wild-type strains (i.e., strains with the gG gene and with or without the gE gene). After amplification by Bst enzyme at a constant temperature of 65°C, a laddering of bright products was visible following electrophoresis on a 2% agarose gel. LAMP was 100–1000-fold more sensitive than the standard PCR. The assay was specific in that it did not amplify other porcine viruses including porcine parvovirus, porcine circovirus type 1, porcine circovirus type 2, porcine reproductive and respiratory syndrome virus, classical swine fever virus, swine transmissible gastroenteritis coronavirus, and porcine epidemic diarrhea virus. Because of its sensitivity, specificity, and simplicity, the LAMP assay could be a useful method for early and rapid differentiation of swine vaccinated with PRV gE-deleted vaccine from swine infected with wild virus.


title: How do Mainland Chinese travelers choose restaurants in Hong Kong? An exploratory study of individual visit scheme travelers and packaged travelers

text: Abstract The introduction of the Individual Visit Scheme (IVS), which allows Mainland Chinese travelers (hereafter called Chinese travelers) to visit Hong Kong on an individual basis, has been beneficial to the fast recovery of the local economy in Hong Kong from severe acute respiratory syndrome (SARS). The IVS travelers, together with the packaged travelers who visited Hong Kong by joining packaged tours, are presently forming the largest segment of inbound travelers to Hong Kong. Despite the significant economic contributions of Chinese travelers to Hong Kong in general, and to the foodservice sector in particular, there has been an absence of prior studies on IVS travelers’ behavior of selecting restaurants in the existing hospitality and tourism literature. This paper reports on an exploratory study that investigated the perceived importance of attributes that pertain to the selection of restaurants from the perspective of IVS and packaged travelers from Mainland China. Empirical findings of a questionnaire survey with 230 Chinese travelers, including 127 IVS travelers and 103 packaged travelers, showed that the respondents in general viewed the included attributes as relatively important. In addition, only two attributes exhibited significant differences between IVS and packaged travelers. Findings of this research would be useful for hospitality and tourism practitioners to better prepare for receiving the growing number of Chinese travelers.


Unequal Distribution of COVID‐19 Risk among Rural Residents by Race and Ethnicity


title: A duplex real-time RT-PCR assay for the detection of California serogroup and Cache Valley viruses

text: A duplex TaqMan real-time RT-PCR assay was developed for the detection of California (CAL) serogroup viruses and Cache Valley virus (CVV), for use in human surveillance. The targets selected for the assay were the sequences encoding the nucleocapsid protein of CAL and the G1 glycoprotein of CVV. Conserved regions were selected by aligning genetic sequences from various strains available in the GenBank database. Primers and probes were selected in conserved regions. The assay sensitivity was 75 gene copies (gc)/reaction for CAL serogroup viruses and 30 gc/reaction for CVV. The performance of the assay was linear over at least 6 log(10) gc. The assay was specific, given that it did not cross-react with a variety of pathogens. It did however, detect 11 viruses within the CAL serogroup, and 12 CVV isolates. The use of an internal control ensured that possible inefficiency in nucleic acid extraction or PCR inhibition would be detected.


title: Enterovirus serotypes in patients with central nervous system and respiratory infections in Viet Nam 1997–2010

text: BACKGROUND: Enteroviruses are the most common causative agents of human illness. Enteroviruses have been associated with regional and global epidemics, recently, including with severe disease (Enterovirus A71 and D68), and are of interest as emerging viruses. Here, we typed Enterovirus A-D (EV) from central nervous system (CNS) and respiratory infections in Viet Nam. METHODS: Data and specimens from prospective observational clinical studies conducted between 1997 and 2010 were used. Species and serotypes were determined using type-specific RT-PCR and viral protein 1 or 4 (VP1, VP4) sequencing. RESULTS: Samples from patients with CNS infection (51 children – 10 CSF and 41 respiratory/rectal swabs) and 28 adults (28 CSF) and respiratory infection (124 children – 124 respiratory swabs) were analysed. Twenty-six different serotypes of the four Enterovirus species (A-D) were identified, including EV-A71 and EV-D68. Enterovirus B was associated with viral meningitis in children and adults. Hand, foot and mouth disease associated Enteroviruses A (EV-A71 and Coxsackievirus [CV] A10) were detected in children with encephalitis. Diverse serotypes of all four Enterovirus species were found in respiratory samples, including 2 polio-vaccine viruses, but also 8 CV-A24 and 8 EV-D68. With the exception of EV-D68, the relevance of these viruses in respiratory infection remains unknown. CONCLUSION: We describe the diverse spectrum of enteroviruses from patients with CNS and respiratory infections in Viet Nam between 1997 and 2010. These data confirm the global circulation of Enterovirus genera and their associations and are important for clinical diagnostics, patient management, and outbreak response. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-0980-0) contains supplementary material, which is available to authorized users.


title: Neuropsychiatric symptoms and quality of life in Spanish Alzheimer’s disease patients during COVID‐19 lockdown

text: BACKGROUND AND PURPOSE: The COVID epidemic is affecting individuals worldwide, and Alzheimer’s disease (AD) and amnesic mild cognitive impairment (MCI) patients are at risk due to their characteristics and age. We analysed the impact of the pandemic on these patients’ neuropsychiatric symptoms and their quality of life after five weeks of lockdown in Spain. METHODS: We tested 40 subjects with a diagnosis of MCI (20) or mild AD (20) from the Cognitive Stimulation Program of Cognitive Disorders Unit. All patients had undergone a previous evaluation during the month before the lockdown, and they were re‐evaluated after 5 weeks of lockdown. The Neuropsychiatric Inventory (NPI) and EuroQol‐5D were used to evaluate the neuropsychiatric symptoms and quality of life of patients and caregivers. RESULTS: The total baseline NPI score was 33.75 (22.28) vs 39.05 (27.96) after confinement (p=0.028). The most frequent neuropsychiatric symptoms affected were apathy (4.15 (3.78) vs 5.75 (4.02); p=0.002) and anxiety (3.95 (3.73) vs 5.30 (4.01); p=0.006) in MCI patients and apathy (2.35 (2.70) vs 3.75 (3.78); p=0.036), agitation (0.45 (1.14) vs 1.50 (2.66); p=0.029) and aberrant motor behaviour (1.25 (2.86) vs 2.00 (2.93); p=0.044) in AD patients. We did not observe differences in EuroQol‐5D scores during the reevaluation. Approximately 30% of patients and 40% of caregivers reported a worsening of their health status during confinement. CONCLUSIONS: We have demonstrated the worsening of neuropsychiatric symptoms in patients with AD and MCI during 5 weeks of lockdown, with agitation, apathy and aberrant motor activity being the most affected symptoms.