title: The US Response to COVID-19 and Climate Change Endangers the Country and the World

text: Climate change and pandemics require cooperative, integrated responses that in turn require planning, coordination, and the mobilization of expertise. US failures in these domains have compromised the world’s ability to cope with both problems. At a minimum, the US needs to re-engage with the Paris Agreement and support the World Health Organization.


title: Recent advancements in combination subunit vaccine development

text: Viral structural proteins share a common nature of homotypic interactions that drive viral capsid formation. This natural process has been mimicked in vitro through recombinant technology to generate various virus-like particles (VLPs) and small subviral particles that exhibit similar structural and antigenic properties of their authentic viruses. Therefore, such self-assembled, polyvalent, and highly immunogenic VLPs and small subviral particles are excellent subunit vaccines against individual viruses, such as the VLP vaccines against the hepatitis B virus, human papilloma virus, and hepatitis E virus, which have already been in the markets. In addition, various antigens and epitopes can be fused with VLPs, small subviral particles, or protein polymers, forming chimeric mono-, bi-, or trivalent vaccines. Owing to their easy-production, un-infectiousness, and polyvalence, the recombinant, chimeric vaccines offer a new approach for development of safe, low-cost, and high efficient subunit vaccines against a single or more pathogens or diseases. While the first VLP-based combination vaccine against malaria has been approved for human use, many others are under development with promising future, which are summarized in this commentary.


PSYCHO-EMOTIONAL CARE IN A NEONATAL UNIT DURING THE COVID-19 PANDEMIC


title: Epidemic intelligence needs of stakeholders in the Asia–Pacific region

text: OBJECTIVE: To understand the global outbreak surveillance needs of stakeholders involved in epidemic response in selected countries and areas in the Asia–Pacific region to inform development of an epidemic observatory, Epi-watch. METHODS: We designed an online, semi-structured stakeholder questionnaire to collect information on global outbreak surveillance sources and limitations from participants who use epidemic intelligence and outbreak alert services in their work in government and nongovernment organizations in the Asia–Pacific region. RESULTS: All respondents agreed that it was important to remain up to date with global outbreaks. The main reason cited for following global outbreak news was as an early warning for serious epidemics. Mainstream media and specialist Internet sources such as the World Health Organization (n = 54/91; 59%), the Program for Monitoring Emerging Diseases (ProMED)-mail (n = 45/91; 49%) and the United States Centers for Disease Control and Prevention (n = 31/91; 34%) were the most common sources for global outbreak news; rapid intelligence services such as HealthMap were less common (n = 9/91; 10%). Only 51% (n = 46/91) of respondents thought that their sources of outbreak news were timely and sufficient for their needs. CONCLUSION: For those who work in epidemic response, epidemic intelligence is important and widely used. Stakeholders are less aware of and less frequently use rapid sources such as HealthMap and rely more on validated but less timely traditional sources of disease surveillance. Users identified a need for more timely and reliable epidemic intelligence.


title: From spatial navigation via visual construction to episodic memory and imagination

text: This hybrid of review and personal essay argues that models of visual construction are essential to extend spatial navigation models to models that link episodic memory and imagination. The starting point is the TAM–WG model, combining the Taxon Affordance Model and the World Graph model of spatial navigation. The key here is to reject approaches in which memory is restricted to unanalyzed views from familiar places, and their later recall. Instead, we will seek mechanisms for imagining truly novel scenes and episodes. We thus introduce a specific variant of schema theory and VISIONS, a cooperative computation model of visual scene understanding in which a scene is represented by an assemblage of schema instances with links to lower-level “patches” of relevant visual data. We sketch a new conceptual framework for future modeling, Visual Integration of Diverse Multi-Modal Aspects, by extending VISIONS from static scenes to episodes combining agents, actions and objects and assess its relevance to both navigation and episodic memory. We can then analyze imagination as a constructive process that combines aspects of memories of prior episodes along with other schemas and adjusts them into a coherent whole which, through expectations associated with diverse episodes and schemas, may yield the linkage of episodes that constitutes a dream or a narrative. The result is IBSEN, a conceptual model of Imagination in Brain Systems for Episodes and Navigation. The essay closes by analyzing other papers in this Special Issue to assess to what extent their results relate to the research proposed here.


title: Protocolo diagnóstico y tratamiento empírico en urgencias de las infecciones respiratorias

text: Acute respiratory infections (ARI), like pneumonia, are the second leading cause of years of live lost and a leading cause of morbidity and mortality in developing countries (WHO). Statistical data show that ARI causes the 30% and 60% of pediatric consultations and represents the 20-40% of pediatric hospital admissions. They account for 63.8% of overall infections treated in emergency department of which, approximately, one quarter involve lower respiratory tract. The most frequent respiratory infections in emergencies, acute bronchitis, COPD flares, bronchiectasis and pneumonia, are analyzed in this protocol.


title: Comparative analysis of the immunogenicity of SARS-CoV nucleocapsid DNA vaccine administrated with different routes in mouse model

text: The development of strategies to augment the immunogenicity of DNA vaccines is critical for improving their clinical utility. One such strategy involves using the different immune routes with DNA vaccines. In the present study, the immunogenicity of SARS-CoV nucleocapsid DNA vaccine, induced by using the current routine vaccination routes (intramuscularly, by electroporation, or orally using live-attenuated Salmonella typhimurium), was compared in mouse model. The comparison between the three vaccination routes indicated that immunization intramuscularly induced a moderate T cell response and antibody response. Mice administrated by electroporation induced the highest antibody response among the three immunization groups and a mid-level of cellular response. In contrast, the orally DNA vaccine evoked vigorous T cell response and a weak antibody production. These results indicated that the distinct types of immune responses were generated by the different routes of DNA immunization. In addition, our results also show that the delivery of DNA vaccines by electroporation and orally using live-attenuated Salmonella in vivo is an effective method to increase the immune responses. Further studies could be carried out using a combination strategy of both oral and electroporation immunizations to stimulate higher cellular and humoral immune responses.


Liability claims in Spain post-COVID-19: a predictable scenario


The higher temperature and ultraviolet, the lower COVID-19 prevalence – Meta-regression of data from large U.S. cities


title: Chapter 25 Diseases Impacting Captive and Free-Ranging Cheetahs

text: Abstract In cheetah, the captive population has historically been beset by multiple degenerative and infectious diseases that have had an impact on cheetah health and breeding programs. In contrast, the free-ranging population has been relatively free of these same diseases. Although research into feline infectious peritonitis mortalities at a few zoos in the early 1980s suggested a possible genetic susceptibility to infectious disease, these diseases have not been noted in genetically similar populations of wild cheetahs despite evidence of exposure to infectious agents. Multidisciplinary and collaborative research has focused on the role of stress in development of disease in captive cheetahs. Subsequent improvements in husbandry and management have lessened the severity of some diseases; however, others remain intractable. As wild populations become increasingly fragmented and managed, it will be important to use the knowledge gained from captive populations to help safeguard their health and to prevent the development of disease in wild-caught cheetahs.


title: Knowledge regarding COVID-19 pandemic in patients with Multiple sclerosis (MS): A report from Iran

text: • 90% of MS patients knew that COVID-19 is in a pandemic stage; • 73% followed quarantine guidelines completely; • All participants believed high person-to-person transmission rate of COVID-19;


title: Looking for Cryptosporidium: the application of advances in detection and diagnosis

text: The protozoan Cryptosporidium is a major public and animal health concern. Young children, immunocompromised people, and pre-weaning animals are especially vulnerable, but treatment options are limited and there is no vaccine. A laboratory diagnosis is required to confirm cases of cryptosporidiosis, and species and genotype determination is essential in distinguishing human from non-human sources, understanding transmission, and strengthening the epidemiological evidence for causative links in outbreaks. However, testing is not consistent, as demonstrated by investigation of a significant increase in cases in some European countries during 2012. Many methods employed are laborious and time-consuming; recent advances, translated into diagnostic assays, can improve testing and facilitate typing to support clinical and environmental investigations.


title: COVID-19 collaborative model for an academic hospital and long-term care facilities

text: Abstract The COVID-19 pandemic is devastating post-acute and long-term care (PA/LTC). As geriatricians practicing in PA/LTC and a regional academic medical center, we created this program for collaboration between academic medical centers and regional PA/LTC facilities. The mission of the geriatric engagement and resource integration in post-acute and long-term care facilities (GERI-PaL) program is to support optimal care of residents in PA/LTC facilities during the COVID-19 pandemic. There are 5 main components of our program: (1) Project ECHO; (2) Nursing liaisons; (3) Infection advisory consultation; (4) Telemedicine consultation; and (5) Resident social contact remote connections. Implementation of this program has had positive response from our local PA/LTC facilities. A key component of our program is our inter-professional team, which includes physicians, nursing, emergency response, and public health experts. With diverse professional backgrounds, our team have created a new model for academic medical centers to collaborate with local PA/LTC facilities.


COVID-19 Fear, Mental Health, and Substance Use Among Israeli University Students


Editorial. A neurosurgery resident’s response to COVID-19: anything but routine


title: Predicting Infectious Disease Using Deep Learning and Big Data

text: Infectious disease occurs when a person is infected by a pathogen from another person or an animal. It is a problem that causes harm at both individual and macro scales. The Korea Center for Disease Control (KCDC) operates a surveillance system to minimize infectious disease contagions. However, in this system, it is difficult to immediately act against infectious disease because of missing and delayed reports. Moreover, infectious disease trends are not known, which means prediction is not easy. This study predicts infectious diseases by optimizing the parameters of deep learning algorithms while considering big data including social media data. The performance of the deep neural network (DNN) and long-short term memory (LSTM) learning models were compared with the autoregressive integrated moving average (ARIMA) when predicting three infectious diseases one week into the future. The results show that the DNN and LSTM models perform better than ARIMA. When predicting chickenpox, the top-10 DNN and LSTM models improved average performance by 24% and 19%, respectively. The DNN model performed stably and the LSTM model was more accurate when infectious disease was spreading. We believe that this study’s models can help eliminate reporting delays in existing surveillance systems and, therefore, minimize costs to society.


title: Under pressure

text: If we aren't sure what causes hypertension, should we really be medicating it, wonders Peter Judge


title: VaccHemInf project: protocol for a prospective cohort study of efficacy, safety and characterisation of immune functional response to vaccinations in haematopoietic stem cell transplant recipients

text: INTRODUCTION: Immune reconstitution after haematopoietic stem cell transplantation (HSCT) is a complex and dynamic process, varying from a state of nearly complete immunosuppression to an expected full immune recovery. Specific vaccination guidelines recommend reimmunisation after HSCT but data regarding vaccine efficacy in this unique population are scarce. New immune functional assays could enable prediction of vaccine response in the setting of HSCT. METHODS AND ANALYSIS: A prospective, longitudinal single-centre cohort study of autologous and allogeneic HSCT recipients was designed in order to determine the vaccine response to five vaccine targets (pneumococcus, hepatitis B virus, Haemophilus Influenzae type b, tetanus and diphtheria) and to correlate it to immune function parameters. A workflow was set up to study serological response to vaccines and to describe the functional immune status of 100 HSCT recipients (50 autologous and 50 allogeneic) before and 3, 12 and 24 months after primary immunisation. At each time point, ‘basic’ immune status recording (serology, immunophenotyping of lymphocyte subsets by flow cytometry) will be assessed. The immune response will furthermore be evaluated before and 3 months after primary vaccination by two ex vivo immune functional assays assessing: (1) tumour necrosis factor alpha, interferon gamma production and host messenger RNA expression on whole-blood stimulation by lipopolysaccharide or Staphylococcus aureus enterotoxin B and (2) T-lymphocyte proliferation in response to a standard mitogen (phytohaemagglutinin) or to selected recall antigens. Reference intervals will be determined from a cohort of 30 healthy volunteers. This translational study will provide data describing vaccine response, immune functionality of HSCT recipients over time and will allow mapping HSCT recipients with regard to their immune function. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the institutional review board (no 69HCL17_0769). Results will be communicated at scientific meetings and submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03659773; Pre-results.


title: Porcine transmissible gastroenteritis virus nonstructural protein 2 contributes to inflammation via NF-κB activation

text: Transmissible gastroenteritis virus (TGEV) infection causes acute enteritis in swine of all ages, and especially in suckling piglets. Small intestinal inflammation is considered a central event in the pathogenesis of TGEV infections, and nuclear factor-kappa B (NF-κB) is a key transcription factor in the inflammatory response. However, it is unclear whether NF-κB is crucial for inducing inflammation during a TGEV infection. Our results show that NF-κB was activated in swine testicular (ST) cells and intestinal epithelial cell lines J2 (IPEC-J2) cells infected with TGEV, which is consistent with the up-regulation of pro-inflammatory cytokines. Treatment of TGEV-infected ST cells and IPEC-J2 cells with the NF-κB-specific inhibitor caused the down-regulation of pro-inflammatory cytokine expression, but did not significantly affect TGEV replication. Individual TGEV protein screening results demonstrated that Nsp2 exhibited a high potential for activating NF-κB and enhancing the expression of pro-inflammatory cytokines. Functional domain analyzes indicated that the first 120 amino acid residues of Nsp2 were essential for NF-κB activation. Taken together, these data suggested that NF-κB activation was a major contributor to TGEV infection-induced inflammation, and that Nsp2 was the key viral protein involved in the regulation of inflammation, with amino acids 1–120 playing a critical role in activating NF-κB. Abbreviations: TCID50: 50% tissue culture infectious dose; DMEM: Dulbecco’s Modified Eagle Medium; eNOS: Endothelial nitric oxide synthase; FBS: fetal bovine serum; IFA: Indirect immunofluorescence; IκB: inhibitor of nuclear factor kappa-B; IL: interleukin; IPEC-J2: intestinal epithelial cell lines J2; IKK: IκB kinase; Luc: luciferase reporter gene; mAbs: monoclonal antibodies; MOI: multiple of infection; Nsp: nonstructural protein; NF-κB: nuclear factor-kappa ; ORFs: open reading frames; PBS: phosphate-buffered saline; p65 p-p65: phosphorylated; RT-PCR: reverse transcription PC; SeV: Sendai virus; ST: swine testicular; TGEV: Transmissible gastroenteritis virus; TNF-α: tumor necrosis factor α; UV-TGEV: Ultraviolet light-inactivated TGEV; ZnF: zinc finger


title: Acyclic nucleoside thiophosphonates as potent inhibitors of HIV and HBV replication

text: 9-[2-(Thiophosphonomethoxy)ethyl]adenine 3 and (R)-9-[2-(Thiophosphonomethoxy)propyl]adenine 4 were synthesized as the first thiophosphonate nucleosides bearing a sulfur atom at the α-position of the acyclic nucleoside phosphonates PMEA and PMPA. Thiophosphonates S-PMEA 3 and S-PMPA 4 were evaluated for in vitro activity against HIV-1 (subtypes A to G), HIV-2 and HBV-infected cells, and found to exhibit potent antiretroviral activity. We showed that their diphosphate forms S-PMEApp 5 and S-PMPApp 6 are readily incorporated by wild-type (WT) HIV-1 RT into DNA and act as DNA chain terminators. Compounds 3 and 4 were evaluated for in vitro activity against a broad panel of DNA and RNA viruses and displayed beside HIV a moderate activity against herpes simplex virus and vaccinia viruses. In order to measure enzymatic stabilities of the target derivatives 3 and 4, kinetic data and decomposition pathways were studied at 37 °C in several media.


title: Development of a duplex real-time RT-PCR for the simultaneous detection and differentiation of Theiler’s murine encephalomyelitis virus and rat theilovirus

text: Abstract Theiler’s murine encephalomyelitis virus (TMEV) and rat theilovirus (RTV), the member of the genus Cardiovirus, are widespread in laboratory mice and rats, and are potential contaminants of biological materials. Cardioviruses infection may cause serious complications in biomedical research. To improve the efficiency of routine screening for Cardioviruses infection, a duplex real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay was developed for simultaneous detection and differentiation of TMEV and RTV. The duplex assay was specific for reference strains of TMEV and RTV, and no cross-reaction was found with seven other rodent viruses. The limits of detection of both TMEV and RTV were 4×101 copies RNA/reaction. Reproducibility was estimated using standard dilutions, with coefficients of variation <3.1%. 439 clinical samples were evaluated by both duplex real-time RT-PCR and conventional RT-PCR. For 439 clinical samples，95 samples were positive for TMEV and 72 samples were positive for RTV using duplex real-time RT-PCR approach, whereas only 77 samples were positive for TMEV and 66 samples were positive for RTV when conventional RT-PCR was applied. Mixed infections were found in 20 samples when analyzed by conventional RT-PCR whereas 30 samples were found to be mixed infection when duplex real-time RT-PCR was applied. This duplex assay provides a useful tool for routine health monitoring and screening of contaminated biological materials of these two viruses.


title: Performance of VivaDiag COVID‐19 IgM/IgG Rapid Test is inadequate for diagnosis of COVID‐19 in acute patients referring to emergency room department

text: From late December 2019 COVID-19 (Coronavirus infectious disease 19) epidemics spread from Wuhan, China, to all over the world, including Italy. This article is protected by copyright. All rights reserved.


title: Special considerations for the management of COVID‐19 pediatric patients in the operating room and pediatric intensive care unit in a tertiary hospital in Singapore

text: COVID‐19 was first identified in Wuhan, China and is caused by the novel coronavirus SARS‐CoV 2. It has now spread rapidly to over 190 countries and territories around the world and has been declared a global pandemic by the World Health Organization. The virus is spread through droplet transmission and currently has a mortality rate of over 4% globally. The pediatric population has been found to be less susceptible to the disease with the majority of children having milder symptoms and only one pediatric death being reported globally so far. Despite this, strategies need to be put in place to prevent further spread of the virus. We present a summary of the general measures implemented at a large adult and pediatric tertiary hospital in Singapore (National University Hospital) as well as the specific strategies in place for the operating room and pediatric intensive care unit.


title: X-ray Structures of the Post-fusion 6-Helix Bundle of the Human Syncytins and their Functional Implications

text: Abstract The retroviral envelope-derived proteins syncytin-1 and syncytin-2 (syn1 and syn2) drive placentation in humans by forming a syncytiotophoblast, a structure allowing for an exchange interface between maternal and fetal blood during pregnancy. Despite their essential role, little is known about the molecular mechanism underlying the syncytins' function. We report here the X-ray structures of the syn1 and syn2 transmembrane subunit ectodomains, featuring a 6-helix bundle (6HB) typical of the post-fusion state of gamma-retrovirus and filovirus fusion proteins. Contrary to the filoviruses, for which the fusion glycoprotein was crystallized both in the post-fusion and in the spring-loaded pre-fusion form, the highly unstable nature of the syncytins' prefusion form has precluded structural studies. We undertook a proline-scanning approach searching for regions in the syn1 6HB central helix that tolerate the introduction of helix-breaker residues and still fold correctly in the pre-fusion form. We found that there is indeed such a region, located two α-helical turns downstream a stutter in the central coiled-coil helix - precisely where the breaks of the spring-loaded helix of the filoviruses map. These mutants were fusion-inactive as they cannot form the 6HB, similar to the “SOSIP” mutant of HIV Env that allowed the high-resolution structural characterization of its labile pre-fusion form. These results now open a new window of opportunity to engineer more stable variants of the elusive pre-fusion trimer of the syncytins and other gamma-retroviruses envelope proteins for structural characterization.


title: Human Coronavirus-HKU1 Infection Among Adults in Cleveland, Ohio

text: BACKGROUND. Human coronaviruses (CoV) have been long recognized as a common cause of respiratory tract disease including severe respiratory tract illness. Coronavirus-HKU1 has been described predominantly among children less than 5 years of age in the United States with few studies characterizing the disease spectrum among adults. METHODS. Nasopharyngeal specimens of patients with respiratory symptoms were analyzed for CoV-HKU1 by NxTAG Respiratory Pathogen Panel multiplex assay from February 7, 2016 to April 30, 2016. Epidemiologic, clinical, and laboratory data were collected on adults (patients >18 years) whose samples screened positive. RESULTS. Of 832 adult respiratory specimens screened, 13 (1.6%) cases of CoV-HKU1 were identified. Adults age ranged between 23 and 75 years and 6 (46%) were males. All of whom had 1 or more respiratory symptoms, and 5 (38%) also reported 1 or more gastrointestinal symptoms. Eleven (85%) reported history of smoking and 5 (38%) used inhaled steroids. Seven (54%) required hospitalization, 5 (71%) of these needed supplemental oxygen, and 2 (29%) were admitted to intensive care. Median length of hospitalization was 5 days. Eight (62%) received antibiotics despite identification of CoV-HKU1. Infectious work-up in 1 patient who died did not reveal any other pathogen. In 2 (15%) CoV-HKU1-positive adults, the only viral coinfection detected was influenza A. CONCLUSIONS. Coronavirus-HKU1 accounted for 1.6% of adult respiratory infections and should be considered in differential diagnosis of severe respiratory illnesses among adults.


title: Ethical and Philosophical Considerations for Gain-of-Function Policy: The Importance of Alternate Experiments

text: The Department of Health and Human Services Framework for Guiding Funding Decisions about Proposed Research Involving Enhanced Potential Pandemic Pathogens (PPPs) contains a series of principles for governing the funding and conduct of gain-of-function (GOF) research resulting in the creation of PPPs. In this article, I address one of these principles, governing the replacement of GOF research with alternate experiments. I argue that the principle fails to address the way that different experiments can promote the same values as those promoted by GOF research resulting in PPPs. I then address some objections to this claim, and provide policy recommendations moving forward.


title: Environmental fate, toxicity and risk management strategies of nanoplastics in the environment: Current status and future perspectives

text: Tiny plastic particles considered as emerging contaminants have attracted considerable interest in the last few years. Mechanical abrasion, photochemical oxidation and biological degradation of larger plastic debris result in the formation of microplastics (MPs, 1 μm to 5 mm) and nanoplastics (NPs, 1 nm to 1000 nm). Compared with MPs, the environmental fate, ecosystem toxicity and potential risks associated with NPs have so far been less explored. This review provides a state-of-the-art overview of current research on NPs with focus on currently less-investigated fields, such as the environmental fate in agroecosystems, migration in porous media, weathering, and toxic effects on plants. The co-transport of NPs with organic contaminants and heavy metals threaten human health and ecosystems. Furthermore, NPs may serve as a novel habitat for microbial colonization, and may act as carriers for pathogens (i.e., bacteria and viruses). An integrated framework is proposed to better understand the interrelationships between NPs, ecosystems and the human society. In order to fully understand the sources and sinks of NPs, more studies should focus on the total environment, including freshwater, ocean, groundwater, soil and air, and more attempts should be made to explore the aging and aggregation of NPs in environmentally relevant conditions. Considering the fact that naturally-weathered plastic debris may have distinct physicochemical characteristics, future studies should explore the environmental behavior of naturally-aged NPs rather than synthetic polystyrene nanobeads.


Reusing N95 (or P2) masks: current evidence and urgent research questions


Antigenic Relatedness of Human Enteric Coronavirus Strains to Human Coronavirus OC43: A Preliminary Report


title: Temporal Trends of In-Hospital Mortality in Patients Treated with Intra-Aortic Balloon Pumping: A Nationwide Population Study in Taiwan, 1998-2008

text: Intra-aortic balloon pumping (IABP) is widely used for hemodynamic support in critical patients with cardiogenic shock (CS). We examined whether the in-hospital mortality of patients in Taiwan treated with IABP has recently declined. We used Taiwan’s National Health Insurance Research Database to retrospectively review the in-hospital all-cause mortality of 9952 (7146 men [71.8%]) 18-year-old and older patients treated with IABP between 1998 and 2008. The mortality rate was 13.84% (n = 1377). The urbanization levels of the hospitals, and the number of days in the intensive care unit, of hospitalization, and of IABP treatment, and prior percutaneous coronary intervention (PCI) were associated with mortality. Seven thousand six hundred thirty-five patients (76.72%) underwent coronary artery bypass grafting (CABG) surgery, and 576 (5.79%) underwent high-risk PCI with IABP treatment. The number of patients treated with IABP significantly increased during this decade (p(trend) < 0.0001), the in-hospital all-cause mortality for patients treated with IABP significantly decreased (p(trend) = 0.0243), but the in-hospital all-cause mortality of patients who underwent CABG and PCI plus IABP did not decrease. In conclusion, the in-hospital mortality rate of IABP treatment decreased annually in Taiwan during the study period. However, high-risk patients who underwent coronary revascularization with IABP had a higher and unstable in-hospital mortality rate.


title: Absence of surface expression of feline infectious peritonitis virus (FIPV) antigens on infected cells isolated from cats with FIP

text: Abstract Feline infectious peritonitis virus (FIPV) positive cells are present in pyogranulomas and exudates from cats with FIP. These cells belong mainly to the monocyte/macrophage lineage. How these cells survive in immune cats is not known. In this study, FIPV positive cells were isolated from pyogranulomas and exudates of 12 naturally FIPV-infected cats and the presence of two immunologic targets, viral antigens and MHC I, on their surface was determined. The majority of the infected cells were confirmed to be cells from the monocyte/macrophage lineage. No surface expression of viral antigens was detected on FIPV positive cells. MHC I molecules were present on all the FIPV positive cells. After cultivation of the isolated infected cells, 52±10% of the infected cells re-expressed viral antigens on the plasma membrane. In conclusion, it can be stated that in FIP cats, FIPV replicates in cells of the monocyte/macrophage lineage without carrying viral antigens in their plasma membrane, which could allow them to escape from antibody-dependent cell lysis.


title: Oral erosions and petechiae during SARS‐CoV‐2 infection

text: An increasing number of reports have been written regarding the cutaneous manifestations during the coronavirus disease-2019 (COVID-19), though knowledge of the possible oral manifestations is still poor. This may be due to a lack of intraoral examinations, which may be caused by a limited availability of the recommended protective measures and the use of telemedical consultations for SARS-CoV-2 infections. This article is protected by copyright. All rights reserved.


title: Interferon-α2b and ribavirin treatment improves outcome in MERS-CoV-infected rhesus macaques

text: The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) is of global concern – causing severe respiratory illness with 97 confirmed cases and 46 deaths(1). Therapeutic interventions have not been evaluated in vivo, thus patient management relies exclusively on supportive care, which given the high case-fatality rate is not highly effective. The rhesus macaque is the only known disease model for MERS-CoV, developing an acute localized-to-widespread pneumonia with transient clinical disease(2,3) that recapitulates mild-to-moderate human MERS-CoV cases(4,5). The combination of interferon-α2b and ribavirin was effective in reducing MERS-CoV replication in vitro(6); therefore, this strategy was initiated 8 h post-infection in the rhesus macaque model. Treated animals did not develop breathing abnormalities and showed no-to-very mild radiographic evidence of pneumonia. Moreover, treated animals showed reduced levels of systemic (serum) and local (lung) proinflammatory markers in addition to reduced viral genome copies, altered gene expression and less severe histopathological changes in the lungs. Taken together, these data suggest that treatment of MERS-CoV infected rhesus macaques with IFN-α2b and ribavirin reduces virus replication, moderates the host response and improves clinical outcome. As these two drugs are already used in combination in the clinic, IFN-α2b and ribavirin should be considered for management of MERS-CoV cases.


title: The international EAN survey on neurological symptoms in patients with COVID‐19 infection

text: BACKGROUND AND PURPOSE: Although the main clinical features of COVID‐19 infection are pulmonary, several associated neurological signs, symptoms and diseases are emerging. Incidence and characteristics of neurological complications are unclear. For this reason, the European Academy of Neurology (EAN) core COVID‐19 Task Force initiated a survey on neurological symptoms observed in patients with COVID‐19 infection. METHODS: A 17‐question on‐line survey was made available on the EAN website and distributed to EAN members and other worldwide physicians starting on April 9(th), 2020. RESULTS: By April 27(th,) 2020, proper data were collected from 2,343 responders (out of 4,199), of whom 82.0% were neurologists, mostly from Europe. Most responders (74.7%) consulted patients with COVID‐19 mainly in emergency rooms and in COVID‐19 units. The majority (67.0%) had evaluated fewer than 10 patients with neurological manifestations of COVID‐19 (neuro COVID‐19). The most frequently reported neurological findings were headache (61.9%), myalgia (50.4%), anosmia (49.2%), ageusia (39.8%), impaired consciousness (29.3%), and psychomotor agitation (26.7%). Encephalopathy and acute cerebrovascular disorders were reported at 21.0%. Neurological manifestations were generally interpreted as being possibly related to COVID‐19, they were most commonly recognized in patients with multiple general symptoms, and occurred at any time during infection. CONCLUSION: Neurologists are currently and actively involved in the management of neurological issues related to the COVID‐19 pandemic. This survey justifies setting up a prospective registry to better capture the prevalence of patients with neuro COVID‐19, neurological disease characteristics and the contribution of neurological manifestations to outcome.


title: Detection of Severe Acute Respiratory Syndrome‐Like, Middle East Respiratory Syndrome‐Like Bat Coronaviruses and Group H Rotavirus in Faeces of Korean Bats

text: Bat species around the world have recently been recognized as major reservoirs of several zoonotic viruses, such as severe acute respiratory syndrome coronavirus (SARS‐CoV), Middle East respiratory syndrome coronavirus (MERS‐CoV), Nipah virus and Hendra virus. In this study, consensus primer‐based reverse transcriptase polymerase chain reactions (RT‐PCRs) and high‐throughput sequencing were performed to investigate viruses in bat faecal samples collected at 11 natural bat habitat sites from July to December 2015 in Korea. Diverse coronaviruses were first detected in Korean bat faeces, including alphacoronaviruses, SARS‐CoV‐like and MERS‐CoV‐like betacoronaviruses. In addition, we identified a novel bat rotavirus belonging to group H rotavirus which has only been described in human and pigs until now. Therefore, our results suggest the need for continuing surveillance and additional virological studies in domestic bat.


title: MERS-coronavirus replication induces severe in vitro cytopathology and is strongly inhibited by cyclosporin A or interferon-α treatment

text: Coronavirus (CoV) infections are commonly associated with respiratory and enteric disease in humans and animals. The 2003 outbreak of severe acute respiratory syndrome (SARS) highlighted the potentially lethal consequences of CoV-induced disease in humans. In 2012, a novel CoV (Middle East Respiratory Syndrome coronavirus; MERS-CoV) emerged, causing 49 human cases thus far, of which 23 had a fatal outcome. In this study, we characterized MERS-CoV replication and cytotoxicity in human and monkey cell lines. Electron microscopy of infected Vero cells revealed extensive membrane rearrangements, including the formation of double-membrane vesicles and convoluted membranes, which have been implicated previously in the RNA synthesis of SARS-CoV and other CoVs. Following infection, we observed rapidly increasing viral RNA synthesis and release of high titres of infectious progeny, followed by a pronounced cytopathology. These characteristics were used to develop an assay for antiviral compound screening in 96-well format, which was used to identify cyclosporin A as an inhibitor of MERS-CoV replication in cell culture. Furthermore, MERS-CoV was found to be 50–100 times more sensitive to alpha interferon (IFN-α) treatment than SARS-CoV, an observation that may have important implications for the treatment of MERS-CoV-infected patients. MERS-CoV infection did not prevent the IFN-induced nuclear translocation of phosphorylated STAT1, in contrast to infection with SARS-CoV where this block inhibits the expression of antiviral genes. These findings highlight relevant differences between these distantly related zoonotic CoVs in terms of their interaction with and evasion of the cellular innate immune response.


title: Microbial profiling does not differentiate between childhood recurrent acute otitis media and chronic otitis media with effusion

text: Abstract Objectives Otitis media (OM) is one of the most frequent diseases of childhood, with a minority of children suffering from recurrent acute otitis media (rAOM) or chronic otitis media with effusion (COME), both of which are associated with significant morbidity. We investigated whether the microbiological profiling could be used to differentiate between these two conditions. Methods Children up to five years of age, with rAOM (n =45) or COME (n =129) and scheduled for tympanostomy tube insertion were enrolled in a prospective study between 2008 and 2009. Middle ear fluids (n =119) and nasopharyngeal samples (n =173) were collected during surgery for bacterial culture and PCR analysis to identify Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, and to detect 15 distinct respiratory viruses. Results The occurrence of bacterial and viral pathogens in middle ear fluids did not significantly differ between patients suffering from rAOM and COME. In both patient cohorts, H. influenzae and rhinovirus were the predominant pathogens in the middle ear and nasopharynx. Nasopharyngeal carriage with two or three bacterial pathogens was associated with the presence of bacteria in middle ear fluid (P =0.04). The great majority of the bacteria isolated from middle ear fluid were genetically identical to nasopharyngeal isolates from the same patient. Conclusions Based on these results, we propose that the common perception that rAOM is associated with recurrent episodes of microbiologically mediated AOM, whereas COME is generally a sterile inflammation, should be reconsidered.


title: Posterior Reversible Encephalopathy Syndrome: A Manifestation of COVID-19 Cytokine Storm

text: Neuroimaging manifestations of COVID-19 are being reported with increasing frequency with recent reports of associated atypical leukoencephalopathies. We add to this literature by describing a COVID-19 + patient who demonstrated imaging findings typical for posterior reversible encephalopathy syndrome (PRES). The inflammatory syndrome associated with novel corona virus infection has shown markedly increased levels of cytokines and inflammatory markers. This has also been described in a proposed mechanism for PRES, where elevated inflammatory markers result in endothelial injury causing interstitial fluid extravasation typical of PRES. We expect that other cases of PRES will be observed in this population given the scope of the Covid-19 pandemic.


title: Novel Antiviral Activities of Obatoclax, Emetine, Niclosamide, Brequinar, and Homoharringtonine

text: Viruses are the major causes of acute and chronic infectious diseases in the world. According to the World Health Organization, there is an urgent need for better control of viral diseases. Repurposing existing antiviral agents from one viral disease to another could play a pivotal role in this process. Here, we identified novel activities of obatoclax and emetine against herpes simplex virus type 2 (HSV-2), echovirus 1 (EV1), human metapneumovirus (HMPV) and Rift Valley fever virus (RVFV) in cell cultures. Moreover, we demonstrated novel activities of emetine against influenza A virus (FLUAV), niclosamide against HSV-2, brequinar against human immunodeficiency virus 1 (HIV-1), and homoharringtonine against EV1. Our findings may expand the spectrum of indications of these safe-in-man agents and reinforce the arsenal of available antiviral therapeutics pending the results of further in vitro and in vivo tests.


title: Chapter 8 Non-Lipidated LC3 is Essential for Mouse Hepatitis Virus Infection

text: Abstract Coronaviruses (CoVs) are enveloped viruses responsible for severe respiratory diseases in birds and mammals. In infected cells they induce double-membrane vesicles (DMVs) and convoluted membranes (CMs), which are thought to be the site of virus replication. Until recently, both the origin of the CoV-induced vesicles and the exact localization of CoV replication remained unknown. It was assumed that the vesicles derive from the endoplasmic reticulum (ER). Nevertheless no conventional protein markers of the ER, ER-to-Golgi intermediate compartment (ERGIC), Golgi, or coatomer proteins could be detected in these structures. Recent data from our laboratory and others shed light on this mystery. It appears that the Mouse Hepatitis Virus (MHV), a prototype CoV, co-opts ERAD tuning vesicles as replication platforms. These vesicles are released from the ER, but do not contain conventional ER markers or coatomer proteins. Rather, they contain ERAD factors such as SEL1L, EDEM1, and OS-9 that are constitutively cleared from the folding compartment by so called ERAD tuning programs, and display non-lipidated LC3 (LC3-I) periferically associated at their limiting membrane. In MHV-infected cells, the ERAD tuning vesicle markers co-localize with viral non-structural proteins and double-stranded RNA, which are DMV markers. The unconventional role of LC3-I in the MHV infection cycle is further supported by the fact that Atg5 and Atg7, both essential proteins for LC3-I to LC3-II conversion and macroautophagy, are dispensable for CoV replication and DMV formation. These new insights into CoV replication might lead to new therapies to treat CoV infections. They also reveal a novel role for LC3, in its non-lipidated form, in both maintenance of cellular proteostasis and viral infection, the latter function supported by recent findings showing involvement of LC3-I in equine arteritis virus replication.


title: Adults at high-risk of severe coronavirus disease-2019 (Covid-19) in Brazil

text: OBJECTIVE: To estimate the proportion and total number of the general adult population who may be at higher risk of severe Covid-19 in Brazil. METHODS: We included 51,770 participants from a nationally representative, household-based health survey (PNS) conducted in Brazil. We estimated the proportion and number of adults (≥ 18 years) at risk of severe Covid-19 by sex, educational level, race/ethnicity, and state based on the presence of one or more of the following risk factors: age ≥ 65 years or medical diagnosis of cardiovascular disease, diabetes, hypertension, chronic respiratory disease, cancer, stroke, chronic kidney disease and moderate to severe asthma, smoking status, and obesity. RESULTS: Adults at risk of severe Covid-19 in Brazil varied from 34.0% (53 million) to 54.5% (86 million) nationwide. Less-educated adults present a 2-fold higher prevalence of risk factors compared to university graduated. We found no differences by sex and race/ethnicity. São Paulo, Rio de Janeiro, Minas Gerais, and Rio Grande do Sul were the most vulnerable states in absolute and relative terms of adults at risk. CONCLUSIONS: Proportion and total number of adults at risk of severe Covid-19 are high in Brazil, with wide variation across states and adult subgroups. These findings should be considered while designing and implementing prevention measures in Brazil. We argue that these results support broad social isolation measures, particularly when testing capacity for SARS-CoV-2 is limited.


title: COVID‐19 pneumonia in a kidney transplant recipient successfully treated with tocilizumab and hydroxychloroquine

text: Coronavirus disease 2019 (COVID‐19) pneumonia has been poorly reported in solid organ transplanted patients; prognosis is uncertain and best management unclear. We describe the case of a 61‐year‐old kidney transplant recipient with several comorbidities who was hospitalized and later received a diagnosis of COVID‐19 pneumonia; the infection was successfully managed with the use of hydroxychloroquine and a single administration of tocilizumab, after immunosuppression reduction; the patient did not require mechanical ventilation. During the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic, transplant clinicians should be readily informed about new cases of COVID‐19 pneumonia in solid organ transplant recipients, with focus on therapeutic strategies employed and their outcome.


Post COVID 19 and food pathways to sustainable transformation


title: Echinoderms provide missing link in the evolution of PrRP/sNPF-type neuropeptide signalling

text: Neuropeptide signalling systems comprising peptide ligands and cognate receptors are evolutionarily ancient regulators of physiology and behaviour. However, there are challenges associated with determination of orthology between neuropeptides in different taxa. Orthologs of vertebrate neuropeptide-Y (NPY) known as neuropeptide-F (NPF) have been identified in protostome invertebrates, whilst prolactin-releasing peptide (PrRP) and short neuropeptide-F (sNPF) have been identified as paralogs of NPY/NPF in vertebrates and protostomes, respectively. Here we investigated the occurrence of NPY/NPF/PrRP/sNPF-related signalling systems in a deuterostome invertebrate phylum – the Echinodermata. Analysis of transcriptome/genome sequence data revealed loss of NPY/NPF-type signalling, but orthologs of PrRP-type neuropeptides and sNPF/PrRP-type receptors were identified in echinoderms. Furthermore, experimental studies revealed that the PrRP-type neuropeptide pQDRSKAMQAERTGQLRRLNPRF-NH(2) is a potent ligand for a sNPF/PrRP-type receptor in the starfish Asterias rubens. Our findings indicate that PrRP-type and sNPF-type signalling systems are orthologous and originated as a paralog of NPY/NPF-type signalling in Urbilateria.


title: Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus

text: A large number of SARS-related coronaviruses (SARSr-CoV) have been detected in horseshoe bats since 2005 in different areas of China. However, these bat SARSr-CoVs show sequence differences from SARS coronavirus (SARS-CoV) in different genes (S, ORF8, ORF3, etc) and are considered unlikely to represent the direct progenitor of SARS-CoV. Herein, we report the findings of our 5-year surveillance of SARSr-CoVs in a cave inhabited by multiple species of horseshoe bats in Yunnan Province, China. The full-length genomes of 11 newly discovered SARSr-CoV strains, together with our previous findings, reveals that the SARSr-CoVs circulating in this single location are highly diverse in the S gene, ORF3 and ORF8. Importantly, strains with high genetic similarity to SARS-CoV in the hypervariable N-terminal domain (NTD) and receptor-binding domain (RBD) of the S1 gene, the ORF3 and ORF8 region, respectively, were all discovered in this cave. In addition, we report the first discovery of bat SARSr-CoVs highly similar to human SARS-CoV in ORF3b and in the split ORF8a and 8b. Moreover, SARSr-CoV strains from this cave were more closely related to SARS-CoV in the non-structural protein genes ORF1a and 1b compared with those detected elsewhere. Recombination analysis shows evidence of frequent recombination events within the S gene and around the ORF8 between these SARSr-CoVs. We hypothesize that the direct progenitor of SARS-CoV may have originated after sequential recombination events between the precursors of these SARSr-CoVs. Cell entry studies demonstrated that three newly identified SARSr-CoVs with different S protein sequences are all able to use human ACE2 as the receptor, further exhibiting the close relationship between strains in this cave and SARS-CoV. This work provides new insights into the origin and evolution of SARS-CoV and highlights the necessity of preparedness for future emergence of SARS-like diseases.


title: Statistical analysis of the impact of environmental temperature on the exponential growth rate of cases infected by COVID-19

text: We perform a statistical analysis for understanding the effect of the environmental temperature on the exponential growth rate of the cases infected by COVID-19 for US and Italian regions. In particular, we analyze the datasets of regional infected cases, derive the growth rates for regions characterized by a readable exponential growth phase in their evolution spread curve and plot them against the environmental temperatures averaged within the same regions, derive the relationship between temperature and growth rate, and evaluate its statistical confidence. The results clearly support the first reported statistically significant relationship of negative correlation between the average environmental temperature and exponential growth rates of the infected cases. The critical temperature, which eliminates the exponential growth, and thus the COVID-19 spread in US regions, is estimated to be T(C) = 86.1 ± 4.3 F(0).


title: Epidemiologic Characteristics, Transmission Chain, and Risk Factors of Severe Infection of COVID-19 in Tianjin, a Representative Municipality City of China

text: This study was performed to describe the epidemiologic characteristics of coronavirus disease 2019 (COVID-19) and explore risk factors for severe infection. Data of all 131 confirmed cases in Tianjin before February 20 were collected. By February 20, a total of 14/16 districts reported COVID-19 cases, with Baodi district reporting the most cases (n = 56). A total of 22 (16.8%) cases had a Wuhan-related exposure. Fever was the most common symptom (82.4%). The median duration of symptom onset to treatment was [1.0 (0.0–4.0) days], the duration of symptom onset to isolation [2.0 (0.0–6.0) days], and the duration of symptom onset to diagnosis [5.0 (2.0–8.0) days]. The analysis of the transmission chain showed two cluster infections with 62 cases infected. Transmission from a family member constituted 42%, usually at the end of transmission chain. Compared with patients with non-severe infections, patients with severe infections were more likely to be male (46.2 vs. 77.3%, P = 0.009) and had a Wuhan-related exposure (14.0 vs. 40.9%, P = 0.004). Multivariate logistic regression showed that male (OR 3.913, 95% CI 1.206, 12.696; P = 0.023) was an independent risk factor for severe infection. This study provides evidence on the epidemic of COVID-19 by analyzing the epidemiological characteristics of confirmed cases in Tianjin. Self-quarantine at an outbreak's early stage, especially for those with high-risk exposures, is conducive to prevent the transmission of infection. Further investigation is needed to confirm the risk factors for severe COVID-19 infection and investigate the mechanisms involved.


No added value of the modified NEWS score to predict clinical deterioration in COVID-19 patients


title: Discourses of disease: Representations of tuberculosis within New Zealand newspapers 2002–2004()

text: This paper critically examines the ways that tuberculosis (TB) has been represented in the print media in New Zealand over recent years (2002–2004). Our broad contention is that, notwithstanding its biomedical reality, TB is socially constructed by, and through, human experience. Further, public health practitioners depend, to a large extent, on the media to alert the public to threats of disease and opportunities for protection. However, the messages conveyed are sometimes neither helpful nor accurate. In our analysis of TB coverage in three major daily newspapers in New Zealand, we enumerate and classify references to the disease, as well as undertake a discursive analysis of the revealed themes. Of the 366 texts we retrieved in the database search, we selected 120 for in-depth analysis. Our examination indicated the importance of bovine TB within the national consciousness, the stigmatised character of TB and the association between TB and immigrants. We observe that newspaper ‘stories’ in general, and commentaries by public health officials in particular, are invariably offered on a ‘case by case’ basis. We conclude that this specificity in time and place avoids more challenging discourses linking TB with deeply embedded determinants of health such as the strong link between TB and poverty.


title: Nanoparticles and the Control of Oral Biofilms

text: Nanoparticles, novel in size, shape, or surface chemistry, may offer additional functional properties to a range of products from drug delivery systems to dental implant coatings. The potential to control oral biofilms through the use of nanoparticles, classified as particles having a size no greater than 100nm, is reviewed in this chapter. Exploitation of the toxic properties of nanoparticles to bacteria, viruses, and fungi, in particular metals and metal oxides and their incorporation into other materials has increased markedly over the past decade. The potential of nanoparticles to control the formation of biofilms within the oral cavity, as a function of their antimicrobial, antiadhesive, and delivery capabilities, is now coming under close scrutiny. Formulation of materials at the nanoscale range does require novel physicochemical and technological approaches. Keywords Nanoparticles, metals, oral infections, biofilm, coatings, antimicrobial, antiadhesive


title: Machine Learning Approaches in COVID-19 Survival Analysis and Discharge Time Likelihood Prediction using Clinical Data

text: Summary As a highly contagious respiratory disease, COVID-19 has yielded high mortality rates since its emergence in December of 2019. As the number of COVID-19 cases soars in epicenters, health officials are warning about the possibility of the designated treatment centers being overwhelmed by coronavirus patients. In this study, several computational techniques are implemented to analyze the survival characteristics of 1182 patients. The computational results agree with the outcome reported in early clinical reports released for a group of patients from China that confirmed a higher mortality rate in men compared to women and in older age groups. The discharge time prediction of COVID-19 patients was also evaluated using different machine learning and statistical analysis methods. The results indicate that the Gradient Boosting survival model outperforms other models for patient survival prediction in this study. This research study is aimed to help health officials make more educated decisions during the outbreak.


title: Degradation of iopromide by combined UV irradiation and peroxydisulfate

text: Abstract The aqueous degradation of iopromide, an iodinated X-ray contrast media (ICM) compound, by the combination of UV254 irradiation and potassium peroxydisulfate (K2S2O8) has been studied in laboratory scale experiments. The influence of various parameters on the performance of the treatment process has been considered, namely the UV irradiation light intensity, the initial concentrations of iopromide and peroxydisulfate, and the initial solution pH. Iopromide degradation increased with UV light intensity and peroxydisulfate concentration, but decreased with initial pH. Under specific conditions complete removal of iopromide was achieved within 30min, and near-complete mineralisation (loss of solution TOC) within 80min. Degradation was believed to be caused by a combination of direct photolysis, sulphate radical attack, and, to a minor degree, direct oxidation by peroxydisulfate. Approximate values for the reaction rate constants have been determined and found to be equal to 1–2×104 M−1 s−1 for sulfate radicals, and 1–2M−2 s−1 for S2O8 2−. Overall compound degradation was observed to follow first-order kinetics where the rate constant decreased with initial solution pH. During the reaction, the solution pH decreased as a consequence of sulfate radical scavenging.


title: Evaluation of sentinel surveillance system for monitoring hand, foot and mouth disease in Hong Kong

text: Summary Objectives A sentinel surveillance system (SSS) was set up in Hong Kong to monitor hand, foot and mouth disease (HFMD) trends. This evaluation assessed the performance of the SSS from 2001 to 2009, and aimed to identify areas for improvement. Study design A retrospective review using structured guidelines for evaluating public health surveillance systems published by the US Centers for Disease Control and Prevention. Methods The effectiveness of the SSS was evaluated using routine service statistics, laboratory surveillance data, and results of an acceptability survey conducted among the sentinel doctors. This information was used to assess various attributes of the SSS including simplicity, flexibility, data quality, usefulness, sensitivity, specificity, positive predictive value (PPV), representativeness, timeliness and acceptability. Results The SSS was simple and flexible with high-quality data. It correlated well with the laboratory surveillance data (P < 0.001) and facilitated early detection of community epidemics. It helped to identify seasonal trends and high-risk groups. Specificity was high (83.4–88.5%), while sensitivity and PPV were borderline satisfactory (38.4–56.8%). The sentinel clinics were representative of the population distribution. The SSS was acceptable to the sentinel doctors, but 17.9–28.2% of them had delays in reporting. Conclusions The SSS is effective for monitoring HFMD trends in Hong Kong, and is useful for initiating preventive measures.


title: Identification and Genetic Characterization of a Novel Respirovirus in Alpine Chamois (Rupicapra rupicapra rupicapra)

text: SIMPLE SUMMARY: The Alpine chamois is a free-living wild ruminant distributed across the mountainous areas of France, Italy, Switzerland, Liechtenstein, Germany, Austria, Slovenia and Croatia. This wide distribution favours interactions with other wild ruminants and livestock, implying the risk of cross-transmission of pathogens. Due to the impact of lung diseases on chamois populations, the investigation of respiratory pathogens is important for wildlife conservation and for the understanding of infection transmission at the livestock–wildlife interface. In the present study, a novel respirovirus was isolated from a chamois with lung lesions and characterized by full-genome sequence and phylogeny. The genome characterization of this novel virus revealed similarities to domestic ruminant respiroviruses, mainly of caprine and ovine origin. Overall, phylogenetic analyses indicated that the chamois virus is distinct from already defined species and suggested that it is a putative novel member of the genus Respirovirus. The present investigation contributes to the knowledge of respiratory infections in wild ruminants and raises questions on the epidemiological link between chamois and other animal species. ABSTRACT: The Respirovirus genus, family Paramamixoviridae, includes respiratory viral pathogens. Here we report the identification and genetic characterization of a respirovirus in an Alpine chamois showing interstitial pneumonia associated with catarrhal bronchopneumonia. The full-genome characterization of this respirovirus, named ChamoisRV/IT2014, revealed low similarities to caprine respirovirus (77.1%), bovine respirovirus (74.5%) and human respirovirus (72.0%). The phylogenetic analyses based on the full-length genome sequence of the novel isolate and reference respirovirus strains showed that ChamoisRV/IT2014 clustered with caprine respirovirus but formed a separate branch. The phylogenetic tree topology of complete large protein amino acid sequences, representing the current species demarcation criterion for Respirovirus genus, showed a 0.05 branch length of ChamoisRV/IT2014 sequence between the nearest node and the tip of the branch, suggesting that this virus belongs to a novel species. This new isolate in a new host species raises several questions to be addressed on the epidemiological role of chamois and the risks of cross-transmission between wild ruminants and livestock.


title: Pediatric Community-Acquired Pneumonia in the United States Changing Epidemiology, Diagnostic and Therapeutic Challenges, and Areas for Future Research

text: Community-acquired pneumonia (CAP) is one of the most common serious infections in childhood. This review focuses on pediatric CAP in the United States and other industrialized nations, specifically highlighting the changing epidemiology of CAP, diagnostic and therapeutic challenges, and areas for further research.


title: Isolation of sequences from a random-sequence expression library that mimic viral epitopes

text: Abstract We describe the use of random peptide sequences for the mapping of antigenic determinants. An oligonucleotide with a completely degenerate sequence of 17 or 23 nucleotides was inserted into a bacterial expression vector. This resulted in an expression library producing random hexa- or octapeptides attached to a β-galactosidase hybrid protein. Mimotopes, or antigenic sequences that mimic an epitope, were selected by immunoscreening of colonies with monoclonal antibodies, which were specific for antigenic sites on the spike protein of the coronavirus transmissible gastroenteritis virus. We report one mimotope for antigenic site II, eight for site III and one for site IV. The site III and site IV mimotopes were closely similar to the corresponding linear epitopes, localized previously in the amino acid sequence of the S protein. An alignment of the site II mimotope and the sequence of the S protein around Trp97, which is substituted in escape mutants, suggests that this mimotope mimics a conformational epitope located around residues 97–103. Applications of mimotopes to epitope mapping, serodiagnosis and vaccine development are discussed.


title: Detection of air and surface contamination by SARS-CoV-2 in hospital rooms of infected patients

text: Understanding the particle size distribution in the air and patterns of environmental contamination of SARS-CoV-2 is essential for infection prevention policies. Here we screen surface and air samples from hospital rooms of COVID-19 patients for SARS-CoV-2 RNA. Environmental sampling is conducted in three airborne infection isolation rooms (AIIRs) in the ICU and 27 AIIRs in the general ward. 245 surface samples are collected. 56.7% of rooms have at least one environmental surface contaminated. High touch surface contamination is shown in ten (66.7%) out of 15 patients in the first week of illness, and three (20%) beyond the first week of illness (p = 0.01, χ(2) test). Air sampling is performed in three of the 27 AIIRs in the general ward, and detects SARS-CoV-2 PCR-positive particles of sizes >4 µm and 1–4 µm in two rooms, despite these rooms having 12 air changes per hour. This warrants further study of the airborne transmission potential of SARS-CoV-2.


title: Autocrine Interferon Priming in Macrophages but Not Dendritic Cells Results in Enhanced Cytokine and Chemokine Production after Coronavirus Infection

text: Coronaviruses efficiently inhibit interferon (IFN) induction in nonhematopoietic cells and conventional dendritic cells (cDC). However, IFN is produced in infected macrophages, microglia, and plasmacytoid dendritic cells (pDC). To begin to understand why IFN is produced in infected macrophages, we infected bone marrow-derived macrophages (BMM) and as a control, bone marrow-derived DC (BMDC) with the coronavirus mouse hepatitis virus (MHV). As expected, BMM but not BMDC expressed type I IFN. IFN production in infected BMM was nearly completely dependent on signaling through the alpha/beta interferon (IFN-α/β) receptor (IFNAR). Several IFN-dependent cytokines and chemokines showed the same expression pattern, with enhanced production in BMM compared to BMDC and dependence upon signaling through the IFNAR. Exogenous IFN enhanced IFN-dependent gene expression in BMM at early times after infection and in BMDC at all times after infection but did not stimulate expression of molecules that signal through myeloid differentiation factor 88 (MyD88), such as tumor necrosis factor (TNF). Collectively, our results show that IFN is produced at early times postinfection (p.i.) in MHV-infected BMM, but not in BMDC, and primes expression of IFN and IFN-responsive genes. Further, our results also show that BMM are generally more responsive to MHV infection, since MyD88-dependent pathways are also activated to a greater extent in these cells than in BMDC.


title: Clinical outcomes of influenza-like illness treated with Chinese herbal medicine: an observational study

text: Abstract OBJECTIVE To present and analyze treatments and clinical outcomes of Chinese patients with influenza-like illness. METHODS We conducted a multi-site observational study from December 2009 to April 2010. Patients with influenza-like illness from 45 hospitals were enrolled. Patients received Chinese herbal medicine (CHM), conventional treatments, or CHM plus conventional treatments (combination treatment) according to the guidelines for influenza A/H1N1 2009 in China. The primary outcomes were the time to alleviation of symptoms and the incidence of complications. The secondary outcomes were the time until becoming afebrile, incidence of severe illness, testing negative on an influenza A viral test, and total medical fees. RESULTS In total, 5967 patients were enrolled. The percentages of patients prescribed CHM alone, conventional treatment, and combination treatment were 27.8%, 5.1%, and 67.7%, respectively. There were no significant differences in the time to alleviation of symptoms, incidence of complications, time to becoming afebrile, or rate of severe illness among the CHM, conventional, and combination treatment groups. The rates of testing negative on the influenza virus A rapid test and H1N1 virus test were 90.3% and 76.3%, respectively. However, significant differences were found in the total medical fees among the three groups: CHM treatments were more economical than the other two treatments. CONCLUSION The efficacy of CHM for influenza-like illness was not different from that of conventional treatments, but it was more economical.


title: Essential covalent linkage between the chymotrypsin-like domain and the extra domain of the SARS-CoV main protease

text: The main protease of the coronavirus causing severe acute respiratory syndrome performs proteolytic processing of the viral polyproteins. The active form of the enzyme is a homodimer with each subunit consisting of three structural domains. Domains I and II, hosting the complete catalytic machinery, constitute the N-terminal chymotrypsin-like folding scaffold and connect to the extra C-terminal domain III by a long loop. Previously, the domain III-truncated enzyme was demonstrated to fold independently into an intact chymotrypsin-like fold, but it showed no enzyme activity. To further delineate the structure–function relationships of the domain III and the long loop, we generated some truncated and mutated M(pro) forms bearing various combinations of the loop with other structural parts of the enzyme. Their conformational and association properties were investigated in detail. Far-ultraviolet circular dichroism (CD) measurements revealed that these fragments could fold independently. The secondary, tertiary and quaternary structures of these mixtures were monitored by CD, fluorescence spectroscopy and analytical ultracentrifugation. However, no enzyme activity was observed for any mutant or mixtures. These observations indicate that the covalent linkage between the chymotrypsin like and the extra domain is essential for enzymatic activity of the main coronavirus protease and for the integrity of its quaternary structure.


title: Potential causes and consequences of gastrointestinal disorders during a SARS-CoV-2 infection

text: Summary Coronaviruses cause several human diseases, including severe acute respiratory syndrome. The global coronaviruses disease 2019 (COVID-19) pandemic has become a huge threat to humans. Intensive research on the pathogenic mechanisms used by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is urgently needed – notably in order to identify potential drug targets. Clinical studies of patients with COVID-19 have shown that gastrointestinal disorders appear to precede or follow the respiratory symptoms. Here, we review gastrointestinal disorders in patients with COVID-19, suggest hypothetical mechanisms leading to gut symptoms, and discuss the potential consequences of gastrointestinal disorders on the outcome of the disease. Lastly, we discuss the role of the gut microbiota during respiratory viral infections and suggest that targeting gut dysbiosis may help to control the pathogenesis of COVID-19.


title: Severe COVID-19 infection in a patient with multiple sclerosis treated with fingolimod

text: Abstract Background : Fingolimod is used for immune therapy in patients with multiple sclerosis. Long-term treatment is associated with a small increase in the risk of herpes virus reactivation and respiratory tract infections. Patients with coronavirus disease 2019 (COVID-19) under Fingolimod treatment have not been described. Methods and results : We report a 57-year old female patient with a relapsing remitting multiple sclerosis under fingolimod treatment who experienced a severe COVID-19 infection in March 2020 (Extended Disability Status Scale: 2.0). Having peripheral lymphopenia typical for fingolimod treatment (total lymphocytes 0.39/nL [1.22-3.56]), the patient developed bilateral interstitial pneumonia with multiple ground-glass opacities on chest CT. Fingolimod medication was stopped. On the intensive care unit, non-invasive ventilation was used to provide oxygen and ventilation support regularly. Over the following two days, oxygenation improved, and the patient was transferred to a normal ward five days after admission. Conclusion : The implications fingolimod has on COVID-19 are complex. As an S1P analogue, fingolimod might enhance lung endothelial cell integrity. In addition, in case of a so-called cytokine storm, immunomodulation might be beneficial to reduce mortality. Future studies are needed to explore the risks and therapeutic effects of fingolimod in COVID-19 patients.


title: Epidemiology of respiratory virus infections among infants and young children admitted to hospital in Oman

text: The aim of this prospective study was to determine the epidemiology of respiratory viruses responsible for seasonal epidemics of influenza‐like illness in infants and young children in Oman. All children ≤5 years of age consecutively admitted to Sultan Qaboos University Hospital in Oman over a 1‐year period between December 2007 and December 2008 with acute respiratory infections were included. A multiplex polymerase chain reaction (PCR) for viral detection was performed on nasopharyngeal aspirates. Analyses were conducted using univariate statistical methods. Of the 259 infants and young children, at least one respiratory virus was detected in 130 samples (50%). The most prevalent viruses were respiratory syncytial virus (RSV; 43%; n = 56), adenovirus (15%; n = 20), and parainfluenza virus (PIV) (11%; n = 14). Dual or multiple viral infections were found in 23 cases (18%). The three most prominent symptoms of the cohort were fever (78%; n = 201), tachypnoea (77%; n = 200), and runny nose (61%; n = 158). The majority had bronchiolitis (39%; n = 101) while 37% (n = 96) had pneumonia. RSV was more likely to affect those that were young (4 months vs. 7.5 months; P = 0.002) and had tachypnoea (93% vs. 69%; P = 0.004), lower respiratory tract infections (91% vs. 80%; P = 0.039), and bronchiolitis (57% vs. 38%; P = 0.024). The study indicated that respiratory viruses are highly prevalent in children ≤5 years presenting with acute respiratory infections in Oman, of which RSV is the most prominent. J. Med. Virol. 84: 1323–1329, 2012. © 2012 Wiley Periodicals, Inc.


title: Thromboinflammation in COVID-19 acute lung injury

text: Since the initial description in 2019, the novel coronavirus SARS-Cov-2 infection (COVID-19) pandemic has swept the globe. The most severe form of the disease presents with fever and shortness of breath, which rapidly deteriorates to respiratory failure and acute lung injury (ALI). COVID-19 also presents with a severe coagulopathy with a high rate of venous thromboembiolism(1). In addition, autopsy studies have revealed co-localized thrombosis and inflammation, which is the signature of thromboinflammation, within the pulmonary capillary vasculature. While the majority of published data is on adult patients, there are parallels to pediatric patients. In our experience as a COVID-19 epicenter, children and young adults do develop both the coagulopathy and the ALI of COVID-19. This review will discuss COVID-19 ALI from a hematological perspective with discussion of the distinct aspects of coagulation that are apparent in COVID-19. Current and potential interventions targeting the multiple thromboinflammatory mechanisms will be discussed.


title: The surgeons and the COVID-19 pandemic.

text: The current world Covid-19 pandemic has been the most discussed topic in the media and scientific journals. Fear, uncertainty, and lack of knowledge about the disease may be the significant factors that justify such reality. It has been known that the disease presents with a rapidly spreading, it is significantly more severe among the elderly, and it has a substantial global socioeconomic impact. Besides the challenges associated with the unknown, there are other factors, such as the deluge of information. In this regard, the high number of scientific publications, encompassing in vitro, case studies, observational and randomized clinical studies, and even systematic reviews add up to the uncertainty. Such a situation is even worse when considering that most healthcare professionals lack adequate knowledge to critically appraise the scientific method, something that has been previously addressed by some authors. Therefore, it is of utmost importance that expert societies supported by data provided by the World Health Organization and the National Health Department take the lead in spreading trustworthy and reliable information. The Brazilian College of Surgeons suggests in this document various initiatives that may help surgeons, healthcare providers, and patients who will have to face a surgical event under the pandemic.


title: Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19)

text: BACKGROUND: The emergence of coronavirus disease 2019 (COVID-19) is a major healthcare threat. The current method of detection involves a quantitative polymerase chain reaction (qPCR)–based technique, which identifies the viral nucleic acids when present in sufficient quantity. False-negative results can be achieved and failure to quarantine the infected patient would be a major setback in containing the viral transmission. We aim to describe the time kinetics of various antibodies produced against the 2019 novel coronavirus (SARS-CoV-2) and evaluate the potential of antibody testing to diagnose COVID-19. METHODS: The host humoral response against SARS-CoV-2, including IgA, IgM, and IgG response, was examined by using an ELISA-based assay on the recombinant viral nucleocapsid protein. 208 plasma samples were collected from 82 confirmed and 58 probable cases (qPCR negative but with typical manifestation). The diagnostic value of IgM was evaluated in this cohort. RESULTS: The median duration of IgM and IgA antibody detection was 5 (IQR, 3–6) days, while IgG was detected 14 (IQR, 10–18) days after symptom onset, with a positive rate of 85.4%, 92.7%, and 77.9%, respectively. In confirmed and probable cases, the positive rates of IgM antibodies were 75.6% and 93.1%, respectively. The detection efficiency by IgM ELISA is higher than that of qPCR after 5.5 days of symptom onset. The positive detection rate is significantly increased (98.6%) when combining IgM ELISA assay with PCR for each patient compared with a single qPCR test (51.9%). CONCLUSIONS: The humoral response to SARS-CoV-2 can aid in the diagnosis of COVID-19, including subclinical cases.


title: Haemorrhagic-fever-like changes and normal chest radiograph in a doctor with SARS

text: Summary A 33-year-old doctor contracted severe acute respiratory syndrome presenting with features of disseminated intravascular coagulopathy without changes in the chest radiograph initially. A CT scan of his chest showed marked lung changes. His condition improved with intravenous methylprednisolone 500 mg daily and ribavirin 1·2 g orally thrice daily. The case illustrates the importance of a break in fever between the viraemic and lung inflammatory phases of the illness that occurs before radiographic changes and which may obscure diagnosis. Careful quarantine and follow-up of these patients are necessary. Coagulopathy is usually uncomplicated and early CT of the chest may elucidate hidden lung changes and facilitate a rapid diagnosis.


title: Extent of prior lung irradiation and mortality in COVID-19 patients with a cancer history

text: PURPOSE: There have been nearly 200,000 deaths from SARS-CoV-2 (COVID-19) worldwide so far. Cancer history appears to be a poor prognostic factor for COVID-19 patients, though the reasons for this are unclear. In this report, we assess if extent of prior lung irradiation is a risk factor for death due to COVID-19 infection. METHODS: Patients who tested positive for COVID-19 between March 14(th) and April 15(th), 2020 at our institution and previously received radiotherapy for cancer in our department were included in this analysis. Patient characteristics and metrics describing the extent of lung irradiation were tabulated. Cox regression models were used to identify predictors of death following COVID-19 diagnosis. A logistic model was used to characterize the association between mean lung radiotherapy dose and 14-day mortality risk following COVID-19 diagnosis. RESULTS: 107 patients met inclusion criteria. With a median follow-up of 7 days from COVID-19 diagnosis for surviving patients, 24 deaths have been observed. The actuarial survival rate 14 days after COVID-19 testing is 66%. Increasing mean lung dose (HR per Gy = 1.1, p=0.002), lung cancer diagnosis (HR=3.0, p=0.034), and receiving radiotherapy between one month and one year before COVID-19 testing (HR = 3.4, p=0.013) were associated with increased risk of death. Our survival model demonstrates a near linear relationship between mortality risk following COVID-19 diagnosis and mean lung radiotherapy dose. CONCLUSIONS: COVID-19 patients with a history of radiotherapy for cancer have a poor prognosis, and mortality risk appears to be associated with extent of lung irradiation. Validation of these findings will be critical as the COVID-19 pandemic continues.


title: Gene expression analysis reveals schizophrenia-associated dysregulation of immune pathways in peripheral blood mononuclear cells

text: Abstract Peripheral blood mononuclear cells (PBMCs) represent an accessible tissue source for gene expression profiling in schizophrenia that could provide insight into the molecular basis of the disorder. This study used the Illumina HT_12 microarray platform and quantitative real time PCR (QPCR) to perform mRNA expression profiling on 114 patients with schizophrenia or schizoaffective disorder and 80 non-psychiatric controls from the Australian Schizophrenia Research Bank (ASRB). Differential expression analysis revealed altered expression of 164 genes (59 up-regulated and 105 down-regulated) in the PBMCs from patients with schizophrenia compared to controls. Bioinformatic analysis indicated significant enrichment of differentially expressed genes known to be involved or associated with immune function and regulating the immune response. The differential expression of 6 genes, EIF2C2 (Ago 2), MEF2D, EVL, PI3, S100A12 and DEFA4 was confirmed by QPCR. Genome-wide expression analysis of PBMCs from individuals with schizophrenia was characterized by the alteration of genes with immune system function, supporting the hypothesis that the disorder has a significant immunological component in its etiology.


title: A roadmap for MERS-CoV research and product development: report from a World Health Organization consultation

text: As part of the World Health Organization (WHO) R&D Blueprint initiative, leading stakeholders on Middle East respiratory syndrome coronavirus (MERS-CoV) convened to agree on strategic public-health goals and global priority research activities that are needed to combat MERS-CoV. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nm.4131) contains supplementary material, which is available to authorized users.


I. Anaesthesia and SARS


SARS‐CoV‐2: Environment and spread: An annotated selection of World Wide Web sites relevant to the topics in environmental microbiology


title: Surveillance for foodborne disease outbreaks in China, 2003 to 2008

text: Abstract Knowledge of implicated food vehicles and contributing factors derived from foodborne disease outbreak (FBDO) investigations allows consumers to be educated on decreasing high-risk behavior to reduce the risk of being affected by foodborne diseases. Food safety regulatory authorities also need summary of outbreak data, as these data indicate where the existing food supply system should be improved. To obtain information on epidemiology of FBDOs in China, FBDOs reported to the China National Foodborne Diseases Surveillance Network by 12 surveillance provinces that include 43% of the Chinese population was summarized. Between 2003 and 2008, 2795 FBDOs were reported, resulting in 62559 illnesses, 31261 hospitalizations, and 330 deaths. Outbreak size ranged from 2 to 464 cases, with a median of 14 cases. The outbreak rate had decreased from 1.37 per 1 million population in 2003 to 0.46 per 1 million population in 2008. Of the 2176 outbreaks with a single known etiology, bacteria (1051 outbreaks, 48%), man-made chemical hazards (550 outbreaks, 25%), and animal and plant toxins (536 outbreaks, 25%) were the main courses. Only one outbreak was caused by virus. Of the 1930 outbreaks with a single commodity, plant-based foods were the most common reported (930 outbreaks, 48%), followed by animal-based foods (590 outbreaks, 31%). Outbreaks most frequently occurred in private residences (32%), workplace cafeterias (21%), and restaurants (17%). The most common factor reported in the 2190 outbreaks with known contributing factors were improper cooking (510 outbreaks, 23%), contaminated ingredient (503 outbreaks, 23%), cross contamination (475 outbreaks, 22%) and improper storage (295 outbreaks, 13%). It is considered that FBDOs continue to be an important public health problem in China.


title: Quality assessment of patient information on orthognathic surgery on the Internet

text: OBJECTIVE: The aim of this study was to assess the quality of online information for patients on orthognathic surgery. MATERIALS AND METHODS: A selection of search terms specific for orthognathic surgery was chosen and 150 websites were identified using the Internet search engines Google, Yahoo and Bing. Irrelevant websites were excluded. The remaining websites were assessed with a modified Ensuring Quality Information for Patients (EQIP) tool. EQIP evaluates the quality of medical patient information by measuring the three key aspects of content, structure, and identification data. RESULTS: 48 relevant websites were indentified. EQIP values ranged between 2 and 28 (median 13.65). While 37 of the 48 websites described details of the surgical procedures, only 13 mentioned possible risks and complications of the surgery. No differences were found between the websites of private practices, dentists and public hospitals, universities, or others (p =0.66). Websites found by Google had a significantly lower EQIP score compared with Yahoo and Bing (11.12 vs. 16.60 for Yahoo and 16.23 for Bing; p = 0.012). The better the rank of the website, the higher the EQIP score (r = −0.411, p = 0.004). CONCLUSIONS: The results of this study reflected a large variation of quality of information on orthognathic surgery on the Internet. Therefore, surgeons must be aware that they might be confronted with unrealistic expectations of patients, who may underestimate the potential risks and drawbacks of orthognathic surgery.


title: Evaluation of COVID 19 infection in 279 cancer patients treated during a 90-day period in 2020 pandemic

text: BACKGROUND: The aim of this study was investigation of COVID-19 disease and its outcome in cancer patients who needed treatment, in a 90-day period. METHODS: Cancer patient who required treatment, were evaluated for potential COVID-19 infection in a 90-day period, starting from beginning of this epidemic in Iran, January, to April 19, 2020. For treatment of solid tumor patients, if they did not have symptoms related to COVID-19, just chest X-ray was requested. If they showed COVID-19 related symptoms, high resolution CT scan of lungs was requested. For hematology cancer patients, PCR test for COVID-19 infection was requested as well. Protection measures were considered for personnel of oncology wards. RESULTS: 279 Patients were followed up in this 90-day period. No COVID-19 infection was observed in 92 cases of breast cancer, 14 cases of gastric cancer and 12 cases of pancreaticobiliary cancer. However, in 72 cases of colon cancer, 11 cases of lung cancer, 5 cases brain tumors and 12 cases ovarian cancer; 4 cases of COVID-19 were observed. In the hematology cancers group, which included 14 cases of Hodgkin’s disease, 23 cases of lymphoproliferative disorder, 12 cases of acute leukemia and 12 cases of multiple myeloma; 3 cases of COVID-19 were observed. CONCLUSION: Patients with cancer who need treatment can be treated by taking some measures. These measures include observing individual and collective protection principles in patients and health-care personnel, increasing patients’ awareness particularly about self-care behavior, performing a COVID-19 test, and taking a chest X-ray, before the treatment starts


title: Respiratory virus associated with surgery in children patients

text: BACKGROUND: Viral respiratory infection (VRI) is a common contraindication to elective surgery. Asymptomatic shedding among pediatric surgery patients (PSPs) could potentially lead to progression of symptomatic diseases and cause outbreaks of respiratory diseases. The aim of this study is to investigate the incidence of infection among mild symptomatic PSP group and asymptomatic PSP group after surgical procedure. METHODS: We collected the induced sputum from enrolled 1629 children (under 18 years of age) with no respiratory symptom prior to pediatric surgery between March 2017 and February 2019. We tested 16 different respiratory virus infections in post-surgery mild symptomatic PSP group and asymptomatic PSP group using a quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) assay panel. We analyzed symptom data and quantitative viral load to investigate the association between viruses, symptoms and viral quantity in qRT-PCR-positive PSPs. RESULTS: Out of 1629 children enrolled, a total of 204 respiratory viruses were present in 171 (10.50%) PSPs including 47 patients with mild symptoms and 124 with no symptoms after surgery. Commonly detected viruses were human rhino/enterovirus (HRV/EV, 42.19%), parainfluenza virus 3 (PIV3, 24.48%), coronavirus (CoV NL63, OC43, HKU1, 11.46%), and respiratory syncytial virus (RSV, 9.9%). PIV3 infection with a higher viral load was frequently found in PSPs presenting with mild symptoms, progressing to pneumonia with radiographic evidence after surgery. HRV/EV were the most commonly detected pathogens in both asymptomatic and mild symptomatic PSPs. CoV (OC43, HKU1) infections with a higher viral load were mostly observed in asymptomatic PSPs progressing to alveolar or interstitial infiltration. CONCLUSIONS: Our study suggested that PIV3 is a new risk factor for VRI in PSPs. Employing a more comprehensive, sensitive and quantitative method should be considered for preoperative testing of respiratory viruses in order to guide optimal surgical timing.


The “SARS-CoV-2 Effect”: An opportunity to reduce general anaesthesia rates for caesarean section?


title: Fractional Dosing of Yellow Fever Vaccine to Extend Supply: A Modeling Study

text: BACKGROUND: The ongoing yellow fever (YF) epidemic in Angola strains the global vaccine supply, prompting WHO to adopt dose sparing for its vaccination campaign in Kinshasa in July–August 2016. Although a 5-fold fractional-dose vaccine is similar to standard-dose vaccine in safety and immunogenicity, efficacy is untested. There is an urgent need to ensure the robustness of fractional-dose vaccination by elucidating the conditions under which dose fractionation would reduce transmission. METHODS: We estimate the effective reproductive number for YF in Angola using disease natural history and case report data. With simple mathematical models of YF transmission, we calculate the infection attack rate (IAR, the proportion of population infected over the course of an epidemic) under varying levels of transmissibility and five-fold fractional-dose vaccine efficacy for two vaccination scenarios: (i) random vaccination in a hypothetical population that is completely susceptible; (ii) the Kinshasa vaccination campaign in July–August 2016 with different age cutoff for fractional-dose vaccines. FINDINGS: We estimate the effective reproductive number early in the Angola outbreak was between 5·2 and 7·1. If vaccine action is all-or-nothing (i.e. a proportion VE of vaccinees receives complete and the remainder receive no protection), n-fold fractionation can dramatically reduce IAR as long as efficacy VE exceeds 1/n. This benefit threshold becomes more stringent if vaccine action is leaky (i.e. the susceptibility of each vaccinee is reduced by a factor that is equal to the vaccine efficacy VE). The age cutoff for fractional-dose vaccines chosen by the WHO for the Kinshasa vaccination campaign (namely, 2 years) provides the largest reduction in IAR if the efficacy of five-fold fractional-dose vaccines exceeds 20%. INTERPRETATION: Dose fractionation is a very effective strategy for reducing infection attack rate that would be robust with a large margin for error in case fractional-dose VE is lower than expected.


title: Small molecule ISRIB suppresses the integrated stress response within a defined window of activation

text: Activation of the integrated stress response (ISR) by a variety of stresses triggers phosphorylation of the α-subunit of translation initiation factor eIF2. P-eIF2α inhibits eIF2B, the guanine nucleotide exchange factor that recycles inactive eIF2•GDP to active eIF2•GTP. eIF2 phosphorylation thereby represses translation. Persistent activation of the ISR has been linked to the development of several neurological disorders, and modulation of the ISR promises new therapeutic strategies. Recently, a small-molecule ISR inhibitor (ISRIB) was identified that rescues translation in the presence of P-eIF2α by facilitating the assembly of more active eIF2B. ISRIB enhances cognitive memory processes and has therapeutic effects in brain-injured mice without displaying overt side effects. While using ISRIB to investigate the ISR in picornavirus-infected cells, we observed that ISRIB rescued translation early in infection when P-eIF2α levels were low, but not late in infection when P-eIF2α levels were high. By treating cells with varying concentrations of poly(I:C) or arsenite to induce the ISR, we provide additional proof that ISRIB is unable to inhibit the ISR when intracellular P-eIF2α concentrations exceed a critical threshold level. Together, our data demonstrate that the effects of pharmacological activation of eIF2B are tuned by P-eIF2α concentration. Thus, ISRIB can mitigate undesirable outcomes of low-level ISR activation that may manifest neurological disease but leaves the cytoprotective effects of acute ISR activation intact. The insensitivity of cells to ISRIB during acute ISR may explain why ISRIB does not cause overt toxic side effects in vivo.


title: CORONAVIRUS‐DAYS IN DERMATOLOGY

text: Severe acute respiratory syndrome‐corona virus‐2 (SARS‐CoV‐2), which causes coronavirus disease 2019 (COVID‐19), is highly contagious and a particularly popular problem in all around the World and also in all departments of every hospital. In order to protect the well‐being of healthcare providers while providing a sufficient workforce to respond to the coronavirus disease (COVID‐19) are vital for pandemic planning. In this article, we will discuss this problem from a dermatological aspect. This article is protected by copyright. All rights reserved.


title: Privilege and burden of im‐/mobility governance: On the reinforcement of inequalities during a pandemic lockdown

text: In order to contain the COVID‐19 pandemic, nation states have focused on governance of im‐/mobilities: Certain mobility restrictions were enforced, while simultaneously some forms of mobility were maintained or even enhanced in order to keep the system running in crisis mode. With a special focus on Austria, we analyze specific politics of im‐/mobilities concerning the organization of paid work and show how the socio‐spatial conditions of who is permitted, denied or urged to work are inextricably linked to inequalities. It becomes apparent that while in principle all bodies are equally dependent on collective social relations and enduring infrastructure, not everybody contributes equally to their maintenance. In fact, the governance of im‐/mobilities follows and reinforces already prevalent inequality regimes based on class, gender and migration relations, thereby differentiating between bodies perceived as highly valuable and worth protecting and those categorized as less valued and potentially disposable.


title: Management of the difficult airway in the COVID‐19 pandemic: Illustrative complex head and neck cancer scenario

text: BACKGROUND: This case highlights challenges in the assessment and management of the “difficult airway” patient in the SARS‐CoV‐2 (COVID‐19) pandemic era. METHODS: A 60‐year‐old male with history of recent transoral robotic surgery resection, free flap reconstruction, and tracheostomy for p16+ squamous cell carcinoma presented with stridor and dyspnea 1 month after decannulation. Careful planning by a multidisciplinary team allowed for appropriate staffing and personal protective equipment, preparations for emergency airway management, evaluation via nasopharyngolaryngoscopy, and COVID testing. The patient was found to be COVID negative and underwent imaging which revealed new pulmonary nodules and a tracheal lesion. RESULTS: The patient was safely transorally intubated in the operating room. The tracheal lesion was removed endoscopically and tracheostomy was avoided. CONCLUSIONS: This case highlights the importance of careful and collaborative decision making for the management of head and neck cancer and other “difficult airway” patients during the COVID‐19 epidemic.


We should beware of ignoring uncomfortable possible truths (a reply to McManus et al)


title: Microbial disinfection capacity of municipal solid waste (MSW) composting

text: The disinfection capacity of a municipal solid waste (MSW) composting plant (Siloda(®)) has been evaluated. In spring and summer, MSW was followed during the composting process from raw material to mature compost and long‐term storage (1 year). Ascaris eggs, Salmonella, Shigella, total streptococci, faecal streptococci, total coliforms, faecal coliforms and Escherichia coli were studied. Disinfection was successful in terms of a decrease in faecal contamination indicators and disappearance of faecal pathogens. Faecal coliform concentrations in raw waste reached 2·1 × 10(8) cfu g(−1) dry weight in spring (CI 95% : 5·2 × 10(7)–3·4 × 10(8)) and 7·2 × 10(8) cfu g(−1) dry weight (1 × 10(8)–1·7 × 10(9)) in summer, and fell to less than 100 cfu g(−1) dry weight within 20 d. Faecal streptococci concentrations reached 8·7 × 10(8) cfu g(−1) dry weight (3·7 × 10(8)–1·3 × 10(9)) in spring and 2·0 × 10(9) cfu g(−1) dry weight (5·6 × 10(8)–3·4 × 10(9)) in summer, and fell to 8·7 × 10(4) cfu g (−1) dry weight (6·9 × 10(4)–1·0 × 10(5)). No seasonal pattern of contamination, mainly of animal origin, was observed. Microbiological quality of finished compost depends on the storage conditions. Therefore, the storage stage should be viewed as part of the composting process. Monitoring disinfection capacity of MSW composting needs to combine several microbial populations.


The 1st Workshop of the Canadian Society for Virology (CSV2016) was a Special Workshop of the 35th Annual Meeting for the American Society for Virology, held on 18 June 2016 on the beautiful Virginia Tech campus in Blacksburg, Virginia. The workshop provided a forum for discussion of recent advances in the field, in an informal setting conducive to interaction with colleagues. CSV2016 featured two internationally-renowned Canadian keynote speakers who discussed translational virology research; American Society for Virology President Grant McFadden (then from University of Florida, now relocated to Arizona State University) who presented his studies of oncolytic poxviruses, while Matthew Miller (McMaster University) reviewed the prospects for a universal influenza vaccine. The workshop also featured a variety of trainee oral and poster presentations, and a panel discussion on the topic of the future of the CSV and virus research in Canada.