title: A framework for One Health research

text: The need for multidisciplinary research to address today's complex health and environmental challenges has never been greater. The One Health (OH) approach to research ensures that human, animal, and environmental health questions are evaluated in an integrated and holistic manner to provide a more comprehensive understanding of the problem and potential solutions than would be possible with siloed approaches. However, the OH approach is complex, and there is limited guidance available for investigators regarding the practical design and implementation of OH research. In this paper we provide a framework to guide researchers through conceptualizing and planning an OH study. We discuss key steps in designing an OH study, including conceptualization of hypotheses and study aims, identification of collaborators for a multi-disciplinary research team, study design options, data sources and collection methods, and analytical methods. We illustrate these concepts through the presentation of a case study of health impacts associated with land application of biosolids. Finally, we discuss opportunities for applying an OH approach to identify solutions to current global health issues, and the need for cross-disciplinary funding sources to foster an OH approach to research.


title: The concept of quarantine in history: from plague to SARS

text: Abstract The concept of ‘quarantine’ is embedded in health practices, attracting heightened interest during episodes of epidemics. The term is strictly related to plague and dates back to 1377, when the Rector of the seaport of Ragusa (then belonging to the Venetian Republic) officially issued a 30-day isolation period for ships, that became 40 days for land travellers. During the next 100 years similar laws were introduced in Italian and in French ports, and they gradually acquired other connotations with respect to their original implementation. Measures analogous to those employed against the plague have been adopted to fight against the disease termed the Great White Plague, i.e. tuberculosis, and in recent times various countries have set up official entities for the identification and control of infections. Even more recently (2003) the proposal of the constitution of a new European monitoring, regulatory and research institution has been made, since the already available system of surveillance has found an enormous challenge in the global emergency of the severe acute respiratory syndrome (SARS). In the absence of a targeted vaccine, general preventive interventions have to be relied upon, including high healthcare surveillance and public information. Quarantine has, therefore, had a rebound of celebrity and updated evidence strongly suggests that its basic concept is still fully valid.


title: Genetic association between a chemokine gene CXCL-10 (IP-10, interferon gamma inducible protein 10) and susceptibility to tuberculosis

text: Abstract Background Previous studies showed that activation of CXCL-10 and other chemokines were prominent in many infectious diseases. These chemokines are components of innate immune response to respiratory tract pathogens. We examined the promoter variants of CXCL-10 and their role in predisposition to tuberculosis (TB). Methods The promoter 1.8kb of CXCL-10 was sequenced in 24 healthy Chinese individuals to identify genetic polymorphisms. Three tagging SNPs in CXCL-10 promoter (−1447A>G, −872G>A, −135G>A) were selected, and genotyping were performed in 240 TB patients and 176 healthy Chinese subjects. Disease associations were examined by χ 2 and Fisher exact test. Results A promoter SNP (−135G>A) with minor allele frequency of 0.1 showed a moderate association with TB both in genotype analysis (p=0.01) and allelic analysis (p=0.03); other tagging SNPs (−1447A>G, −872G>A) were not associated with TB. The odd ratio of the protective allele −135G>A was 0.51(C.I 0.29 −0.91) for homozygotes and heterozygotes carriers of the A allele. Conclusion A new potential protective SNP (−135G>A) for TB is identified in the promoter of chemokine gene, CXCL-10. Interestingly, the exact same allele has been shown to enhance IP-10 transactivation and susceptibility to Hepatitis B virus infection in a recent publication. This SNP, located at 14bp upstream of a NF-kB binding site, might also account for the susceptibility to TB. Our results expanded the clinical significance of this SNP in CXCL-10 promoter.


title: Protein-protein interactions of human viruses

text: Abstract Viruses infect their human hosts by a series of interactions between viral and host proteins, indicating that detailed knowledge of such virus-host interaction interfaces are critical for our understanding of viral infection mechanisms, disease etiology and the development of new drugs. In this review, we primarily survey human host-virus interaction data that are available from public databases following the standardized PSI-MS format. Notably, available host-virus protein interaction information is strongly biased toward a small number of virus families including herpesviridae, papillomaviridae, orthomyxoviridae and retroviridae. While we explore the reliability and relevance of these protein interactions we also survey the current knowledge about viruses functional and topological targets. Furthermore, we assess emerging frontiers of host-virus protein interaction research, focusing on protein interaction interfaces of hosts that are infected by different viruses and viruses that infect multiple hosts. Finally, we cover the current status of research that investigates the relationships of virus-targeted host proteins to other comorbidities as well as the influence of host-virus protein interactions on human metabolism.


title: Intermediate conformations during viral fusion glycoprotein structural transition

text: Entry of enveloped viruses into cells requires the fusion of viral and cellular membranes, driven by conformational changes in viral glycoproteins. Three different classes of viral fusion proteins have been hitherto identified based on common structural elements. Crystal structures have provided static pictures of pre-fusion and post-fusion conformations of these proteins and have revealed the dramatic reorganization of the molecules, but the transition pathway remains elusive. In this review, we will focus on recent data aiming to characterize intermediate structures during the conformational change. All these data support the existence of a pre-hairpin intermediate, but its oligomeric status is still a matter of debate.


title: Imaging in Severe Acute Respiratory Syndrome (SARS)

text: Abstract Severe acute respiratory syndrome (SARS) is a highly infectious disease caused by a novel coronavirus, and has become pandemic within a short period of time. Imaging plays an important role in the diagnosis, management and follow-up of patients with SARS. The current status of imaging in SARS is presented in this review.


title: Infants hospitalized for Bordetella pertussis infection commonly have respiratory viral coinfections

text: BACKGROUND: Whether viral coinfections cause more severe disease than Bordetella pertussis (B. pertussis) alone remains unclear. We compared clinical disease severity and sought clinical and demographic differences between infants with B. pertussis infection alone and those with respiratory viral coinfections. We also analyzed how respiratory infections were distributed during the 2 years study. METHODS: We enrolled 53 infants with pertussis younger than 180 days (median age 58 days, range 17–109 days, 64.1% boys), hospitalized in the Pediatric Departments at “Sapienza” University Rome and Bambino Gesù Children’s Hospital from August 2012 to November 2014. We tested in naso-pharyngeal washings B. pertussis and 14 respiratory viruses with real-time reverse-transcriptase-polymerase chain reaction. Clinical data were obtained from hospital records and demographic characteristics collected using a structured questionnaire. RESULTS: 28/53 infants had B. pertussis alone and 25 viral coinfection: 10 human rhinovirus (9 alone and 1 in coinfection with parainfluenza virus), 3 human coronavirus, 2 respiratory syncytial virus. No differences were observed in clinical disease severity between infants with B. pertussis infection alone and those with coinfections. Infants with B. pertussis alone were younger than infants with coinfections, and less often breastfeed at admission. CONCLUSIONS: In this descriptive study, no associations between clinical severity and pertussis with or without co-infections were found. TRIAL REGISTRATION: Policlinico Umberto I: protocol 213/14, 3085/13.02.2014, retrospectively registered. Bambino Gesù Children’s Hospital: protocol n. RF-2010-2317709.


title: A Review of Acute Myocardial Injury in Coronavirus Disease 2019

text: In December 2019, an outbreak of pneumonia caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), occurred in Wuhan, Hubei province, China, and it has spread rapidly across the world, causing the coronavirus disease 2019 (COVID-19) pandemic. Although SARS-CoV-2 infection predominantly results in pulmonary issues, accumulating evidence suggests the increased frequency of a variety of cardiovascular complications in patients with COVID-19. Acute cardiac injury, defined as elevated cardiac troponin levels, is the most reported cardiac abnormality in COVID-19 and strongly associated with mortality. In this article, we summarize the currently available data on the association of SARS-CoV-2 and COVID-19 with acute myocardial injury.


title: Structural definition of a conserved neutralization epitope on HIV-1 gp120

text: The remarkable diversity, glycosylation and conformational flexibility of the human immunodeficiency virus type 1 (HIV-1) envelope (Env), including substantial rearrangement of the gp120 glycoprotein upon binding the CD4 receptor, allow it to evade antibody-mediated neutralization. Despite this complexity, the HIV-1 Env must retain conserved determinants that mediate CD4 binding. To evaluate how these determinants might provide opportunities for antibody recognition, we created variants of gp120 stabilized in the CD4-bound state, assessed binding of CD4 and of receptor-binding-site antibodies, and determined the structure at 2.3 Å resolution of the broadly neutralizing antibody b12 in complex with gp120. b12 binds to a conformationally invariant surface that overlaps a distinct subset of the CD4-binding site. This surface is involved in the metastable attachment of CD4, before the gp120 rearrangement required for stable engagement. A site of vulnerability, related to a functional requirement for efficient association with CD4, can therefore be targeted by antibody to neutralize HIV-1.


title: Adapting to a Pandemic — Conducting Oncology Trials during the SARS-CoV-2 Pandemic

text: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has necessitated changes in cancer care delivery as resources are reallocated. Clinical trials and other research activities are inevitably impacted. Start-up activities for new trials may be deferred and recruitment suspended. For patients already enrolled however, there are challenges in continuing treatment on trial. Regulatory bodies have issued guidance on managing clinical trials during the pandemic, including contingency measures for remote study visits, delivery of investigational product, and site monitoring visits. New cancer clinical trial practices during the SARS-CoV-2 pandemic include new risk assessment strategies, decentralized and remote trial coordination, data collection, and delegation of specific therapeutic activities. This experience could provide evidence of more feasible and cost-effective methods for future clinical trial conduct.


title: A united statement of the global chiropractic research community against the pseudoscientific claim that chiropractic care boosts immunity

text: BACKGROUND: In the midst of the coronavirus pandemic, the International Chiropractors Association (ICA) posted reports claiming that chiropractic care can impact the immune system. These claims clash with recommendations from the World Health Organization and World Federation of Chiropractic. We discuss the scientific validity of the claims made in these ICA reports. MAIN BODY: We reviewed the two reports posted by the ICA on their website on March 20 and March 28, 2020. We explored the method used to develop the claim that chiropractic adjustments impact the immune system and discuss the scientific merit of that claim. We provide a response to the ICA reports and explain why this claim lacks scientific credibility and is dangerous to the public. More than 150 researchers from 11 countries reviewed and endorsed our response. CONCLUSION: In their reports, the ICA provided no valid clinical scientific evidence that chiropractic care can impact the immune system. We call on regulatory authorities and professional leaders to take robust political and regulatory action against those claiming that chiropractic adjustments have a clinical impact on the immune system.


Radiotherapy & oncology during the COVID-19 pandemic


title: In vivo and in vitro models of demyelinating diseases II. Persistence and host-regulated thermosensitivity in cells of neural derivation infected with mouse hepatitis and measles viruses

text: Abstract Following inoculation of continuous cell lines of neural and other derivations, persistent infections are established with facility by mouse hepatitis and measles viruses. This occurs equally with the prototype MHV3 and its neurotropic variant JHM as well as with the Edmonston vaccine and SSPE Hallé measles variants. In almost every instance that the infection becomes persistent at 32.5°, virus replication is found to be thermosensitive at 39.5°; however, progeny virus derived from such infections at 32.5° is itself thermostable when replicating in the indicator, fully permissive cell lines. The new data, therefore, reveal the existence of a host-conferred interrelationship between persistence and virus restriction at elevated temperature. They indicate that the two agents with neurotropic potential, when they become established as pathogens in the nervous system, could be under close host cell regulation involving as yet unknown mechanisms.


title: The crystal structure of main protease from mouse hepatitis virus A59 in complex with an inhibitor

text: Abstract Mouse hepatitis virus A59 (MHV-A59) is a representative member of the genus betacoronavirus within the subfamily Coronavirinae, which infects the liver, brain and respiratory tract. Through different inoculation routes, MHV-A59 can provide animal models for encephalitis, hepatitis and pneumonia to explore viral life machinery and virus-host interactions. In viral replication, non-structural protein 5 (Nsp5), also termed main protease (Mpro), plays a dominant role in processing coronavirus-encoded polyproteins and is thus recognized as an ideal target of anti-coronavirus agents. However, no structure of the MHV-A59 Mpro has been reported, and molecular exploration of the catalysis mechanism remains hindered. Here, we solved the crystal structure of the MHV-A59 Mpro complexed with a Michael acceptor-based inhibitor, N3. Structural analysis revealed that the Cβ of the vinyl group of N3 covalently bound to C145 of the catalytic dyad of Mpro, which irreversibly inactivated cysteine protease activity. The lactam ring of the P1 side chain and the isobutyl group of the P2 side chain, which mimic the conserved residues at the same positions of the substrate, fit well into the S1 and S2 pockets. Through a comparative study with Mpro of other coronaviruses, we observed that the substrate-recognition pocket and enzyme inhibitory mechanism is highly conservative. Altogether, our study provided structural features of MHV-A59 Mpro and indicated that a Michael acceptor inhibitor is an ideal scaffold for antiviral drugs.


title: Evaluation of a recombination-resistant coronavirus as a broadly applicable, rapidly implementable vaccine platform

text: Emerging and re-emerging zoonotic viral diseases are major threats to global health, economic stability, and national security. Vaccines are key for reducing coronaviral disease burden; however, the utility of live-attenuated vaccines is limited by risks of reversion or repair. Because of their history of emergence events due to their prevalence in zoonotic pools, designing live-attenuated coronavirus vaccines that can be rapidly and broadly implemented is essential for outbreak preparedness. Here, we show that coronaviruses with completely rewired transcription regulatory networks (TRNs) are effective vaccines against SARS-CoV. The TRN-rewired viruses are attenuated and protect against lethal SARS-CoV challenge. While a 3-nt rewired TRN reverts via second-site mutation upon serial passage, a 7-nt rewired TRN is more stable, suggesting that a more extensively rewired TRN might be essential for avoiding growth selection. In summary, rewiring the TRN is a feasible strategy for limiting reversion in an effective live-attenuated coronavirus vaccine candidate that is potentially portable across the Nidovirales order.


title: Involvement of LSECtin in the hepatic natural killer cell response

text: Abstract Accumulating evidence has indicated that natural killer cells (NK cells) play an important role in immune responses generated in the liver. However, the underlying molecular basis for local immune regulation is poorly understood. Mice were intraperitoneally injected with polyinosinic-polycytidylic acid (PolyI:C) at a dose of 20 mg/kg body wt. The percentage and absolute number of NK cells in the liver were analysed with flow cytometry. LSECtin knockout mice and LSECtin cDNA plasmids were used for analyze the role of LSECtin in hepatic NK cell regulation in vivo. Here, we show that the C-type lectin LSECtin, a member of the DC-SIGN family, is a novel liver regulator for NK cells. LSECtin could bind to NK cells in a carbohydrate-dependent manner and could regulate the number of hepatic NK cells. In the NK cell-mediated acute liver injury model induced with PolyI:C, the exogenous expression of LSECtin accelerated NK cell-induced liver injury, whereas the absence of LSECtin ameliorated this condition. Our results reveal that LSECtin is a novel, liver-specific NK cell regulator that may be a target for the treatment of inflammatory diseases in the liver.


title: Loss of IKK subunits limits NF-κB signaling in reovirus infected cells

text: Viruses commonly antagonize innate immune pathways that are primarily driven by Nuclear Factor-κB (NF-κB), Interferon Regulatory Factor (IRF) and Signal Transducer and Activator of Transcription (STAT) family of transcription factors. Such a strategy allows viruses to evade immune surveillance and maximize their replication. Using an unbiased RNA-seq based approach to measure gene expression induced by transfected viral genomic RNA (vgRNA) and reovirus infection, we discovered that mammalian reovirus inhibits host cell innate immune signaling. We found that while vgRNA and reovirus infection both induce a similar IRF dependent gene expression program, gene expression driven by the NF-κB family of transcription factors is lower in infected cells. Potent agonists of NF-κB, such as Tumor Necrosis Factor alpha (TNFα) and vgRNA, failed to induce NF-κB dependent gene expression in infected cells. We demonstrate that NF-κB signaling is blocked due to loss of critical members of the Inhibitor of KappaB Kinase (IKK) complex, NF-κB Essential MOdifier (NEMO) and IKKβ. The loss of the IKK complex components prevents nuclear translocation and phosphorylation of NF-κB, thereby preventing gene expression. Our studies demonstrate that reovirus infection selectively blocks NF-κB, likely to counteract its antiviral effects and promote efficient viral replication. IMPORTANCE Host cells mount a response to curb virus replication in infected cells and prevent infection of neighboring, as yet uninfected cells. The NF-κB family of proteins is important for the cell to mediate this response. In this study, we show that in cells infected with mammalian reovirus, NF-κB is inactive. Further, we demonstrate that NF-κB is rendered inactive because virus infection results in reduced levels of upstream intermediaries (called IKKs) that are needed for NF-κB function. Based on previous evidence that active NF-κB limits reovirus infection, we conclude that inactivating NF-κB is a viral strategy to produce a cellular environment that is favorable for virus replication.


The Heart in the Time of the ‘Coronavirus’


title: Immunodeficiencies Caused by Infectious Diseases

text: Immunodeficiencies caused by infectious agents may result from disruption of normal host barriers or dysregulation of cellular immunity, the latter serving to promote survival of the infectious agent through immune evasion. Such infections may be followed by opportunistic infections with a variety of other microorganisms. Classic infectious causes of immunodeficiency in companion animals are the immunodeficiency retroviruses, including feline immunodeficiency virus and feline leukemia virus. Other important causes include canine distemper virus; canine parvovirus 2; feline infectious peritonitis virus; rickettsial organisms that infect leukocytes; Leishmania; and fungal pathogens, such as Cryptococcus. Considerable research effort has been invested in understanding the mechanisms of pathogen-induced immunosuppression, with the hope that effective therapies may be developed that reverse the immunodeficiencies developed and in turn assist the host to clear persistent or life-threatening infectious diseases.


title: Pulmonary toxicity and inflammatory response of e-cigarettes containing medium-chain triglyceride oil and vitamin E acetate: Implications in the pathogenesis of EVALI but independent of SARS-COV-2 COVID-19 related proteins

text: Recently, there has been an outbreak associated with the use of e-cigarette or vaping products, associated lung injury (EVALI). The primary components of vaping products, vitamin E acetate (VEA) and medium-chain triglycerides (MCT) may be responsible for acute lung toxicity. Currently, little information is available on the physiological and biological effects of exposure to these products. We hypothesized that these e-cig cartridges and their constituents (VEA and MCT) induce pulmonary toxicity, mediated by oxidative damage and inflammatory responses, leading to acute lung injury. We studied the potential mechanisms of cartridge aerosol induced inflammatory response by evaluating the generation of reactive oxygen species by MCT, VEA, and cartridges, and their effects on the inflammatory state of pulmonary epithelium and immune cells both in vitro and in vivo. Cells exposed to these aerosols generated reactive oxygen species, caused cytotoxicity, induced epithelial barrier dysfunction, and elicited an inflammatory response. Using a murine model, the parameters of acute toxicity to aerosol inhalation were assessed. Infiltration of neutrophils and lymphocytes was accompanied by significant increases in IL-6, eotaxin, and G-CSF in the bronchoalveolar lavage fluid (BALF). In mouse plasma, eicosanoid inflammatory mediators, leukotrienes, were significantly increased. Plasma from e-cig users also showed increased levels of hydroxyeicosatetraenoic acid (HETEs) and various eicosanoids. Exposure to e-cig cartridge aerosols showed the most significant effects and toxicity compared to MCT and VEA. In addition, we determined at SARS-COV-2 related proteins and found no impact associated with aerosol exposures from these tested cartridges. Overall, this study demonstrates acute exposure to specific e-cig cartridges induces in vitro cytotoxicity, barrier dysfunction, and inflammation and in vivo mouse exposure induces acute inflammation with elevated pro-inflammatory markers in the pathogenesis of EVALI.


title: The impact of COVID-19 on shoulder and elbow trauma. An Italian survey

text: Abstract Background Because of the rapid spreading of COVID-19, on March 8th, Italy became a "protected area": people are told not to leave their homes unless for an essential reason. Aim of this study was to evaluate the activity of our Trauma Centre, relative to shoulder and elbow, in 30 days starting from March 8th, 2020, the first day of restrictions in Italy, and to compare it with the same days of 2019 to weight the impact of Covid-19 on the shoulder and elbow trauma. Materials and methods Patients managed in our Trauma Centre between 8th March 2020 and 8th April 2020 (COVID-19 period) for a shoulder and elbow trauma were retrospectively included and compared to patients admitted in the same period of 2019 (no COVID-19 period).Clinical records of all participants were examined to obtain information regarding age, sex, mechanism of injury, diagnosis. Results During no COVID-19 period, 133 patients were admitted for a shoulder or elbow trauma; in the COVID period, patients were 47(65% less first aid). In the no-COVID and COVID period, patients with shoulder contusion were 60 (14.78% of all) (M:34; F:26) (mean age: 51.8yrs; range: 18-88) and 11 (12.09% of all contusions) (M:7; F:4) (mean age: 43yrs; range: 24-60), respectively. In the no-COVID period, 27 fractures (9.34% of all fractures) involved the shoulder, while 18 fractures (8.69%) were registered in the COVID period. In the no-COVID period,14 elbow fractures were treated (4.8% of all fractures), and 4 in the COVID period. In the no-COVID and COVID periods, 6 (M:5; F:1) (mean age: 42yrs; range 21-64) and 2 (M: 1; F: 1) (mean age: 29.5yrs; range: 24-35 ) patients reported having the feeling of momentary post-traumatic shoulder instability; at the elbow, patients were 0 and 1 (M: 1; F: 0) (age: 56yrs), respectively. Finally, first or recurrent dislocations in the no-COVID period were 10 and 7 in the COVID period.; in the no-COVID period, elbow dislocations were 2, and 3 in the COVID-period. Conclusions During the COVID period, we provided a reduced number of health services, especially for patients with low energy trauma and for those who underwent sports and traffic accidents. However, during the COVID period, elderly subjects remain exposed to shoulder and elbow trauma due to low-energy (domestic) falls. The subsequent hospitalization of these patients has contributed to making more difficult the management of the hospital wards, partly occupied by COVID-19 patients.


title: Symmetric chest pressure ulcers, consequence of prone position ventilation in a patient with COVID‐19

text: First cases of pneumonia with unknown cause were reported in Wuhan, China, in December 2019(1). The new pathogen, called SARS‐CoV‐2, has rapidly spread reaching the level of a pandemic disease. The worldwide diffusion of coronavirus disease 2019 (COVID‐19) is characterized by various clinical presentations and different related complications. This disease exacerbates in some patients and causes pulmonary edema, multiple organ failure and acute respiratory distress syndrome.


title: Human rhinovirus C infections mirror those of human rhinovirus A in children with community-acquired pneumonia

text: Abstract Background Human rhinoviruses (HRVs) are among the most common causes of community-acquired pneumonia (CAP) in children. However, the differential roles of the three HRV species HRV-A, HRV-B, and HRV-C in pediatric CAP are not fully understood. Objective To determine the distribution of HRV species and their roles in children hospitalized with CAP in Beijing, China. Study design Nasopharyngeal aspirates were collected between April 2007 and March 2008 from 554 children with a primary diagnosis of CAP. HRVs in the clinical samples were detected by RT-PCR and by sequencing. Infections with other respiratory viruses were identified by PCR. Results HRVs were detected in 99 patients (17.87%). Among these patients, 51.52% tested positive for HRV-A, 38.38% for HRV-C, and 10.10% for HRV-B. HRVs were detected throughout the study period. The monthly distribution of HRV infections varied with HRV species. Median age, gender, symptoms, severity, and duration of hospitalization for single HRV-C infections were similar to those observed for single HRV-A infections. Co-infections with other respiratory viruses were detected in 57.58% of the HRV-positive children. HRV/RSV dual infections were correlated with a higher frequency of shortness of breath (HRV-A group, P 2tail =0.01; HRV-C group, P 2tail =0.015) and lower median ages (HRV-A group, P 2tail =0.049; HRV-C group, P 2tail =0.009). Conclusion Our study shows that HRV-C strains circulate at a prevalence intermediate between HRV-A and HRV-B. The severity of clinical manifestations for HRV-C is comparable to that for HRV-A in children with CAP. These findings point to an important role of both HRV-A and HRV-C in pediatric CAP.


title: Natural Disasters

text: Abstract Natural disasters are the result of a hazard overwhelming highly vulnerable community, often resulting in mortality and morbidity. Over the past decade, over 300 natural disasters occur yearly around the world affecting millions and cost billions. The disaster cycle is a framework used to base a coordinated plan to respond, recover, prevent, and prepare for a disaster. Access to clean water, proper sanitation, food/nutrition, shelter, and the threat of communicable diseases are concerns that have the potential to be detrimental to the management of a natural disaster, slowing the recovery process.


title: Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)?

text: Abstract The emergent outbreak of coronavirus disease 2019 (COVID-19) has caused a global pandemic. Acute respiratory distress syndrome (ARDS) and multiorgan dysfunction are among the leading causes of death in critically ill patients with COVID-19. The elevated inflammatory cytokines suggest that a cytokine storm, also known as cytokine release syndrome (CRS), may play a major role in the pathology of COVID-19. However, the efficacy of corticosteroids, commonly utilized antiinflammatory agents, to treat COVID-19-induced CRS is controversial. There is an urgent need for novel therapies to treat COVID-19-induced CRS. Here, we discuss the pathogenesis of severe acute respiratory syndrome (SARS)-induced CRS, compare the CRS in COVID-19 with that in SARS and Middle East respiratory syndrome (MERS), and summarize the existing therapies for CRS. We propose to utilize interleukin-6 (IL-6) blockade to manage COVID-19-induced CRS and discuss several factors that should be taken into consideration for its clinical application.


title: Stability of RNA sequences derived from the coronavirus genome in human cells

text: Abstract Most viruses inhibit the innate immune system and/or the RNA degradation processes of host cells to construct an advantageous intracellular environment for their survival. Characteristic RNA sequences within RNA virus genomes or RNAs transcribed from DNA virus genomes contribute toward this inhibition. In this study, we developed a method called “Fate-seq” to comprehensively identify the RNA sequences derived from RNA and DNA viruses, contributing RNA stability in the cells. We examined the stabilization activity of 5,924 RNA fragments derived from 26 different viruses (16 RNA viruses and 10 DNA viruses) using next-generation sequencing of these RNAs fused 3′ downstream of GFP reporter RNA. With the Fate-seq approach, we detected multiple virus-derived RNA sequences that stabilized GFP reporter RNA, including sequences derived from severe acute respiratory syndrome-related coronavirus (SARS-CoV). Comparative genomic analysis revealed that these RNA sequences and their predicted secondary structures are highly conserved between SARS-CoV and the novel coronavirus, SARS-CoV-2, which is responsible for the global outbreak of the coronavirus-associated disease that emerged in December 2019 (COVID-19). These sequences have the potential to enhance the stability of viral RNA genomes, thereby augmenting viral replication efficiency and virulence.


title: Feline Infectious Peritonitis Viruses Arise by Mutation from Endemic Feline Enteric Coronaviruses

text: Abstract Feline infectious peritonitis virus (FIPV) strains from six cats and three different geographic areas were compared genetically with feline enteric coronavirus (FECV) isolates obtained from cats inhabiting the same environments. Sequence comparisons were made from 1.2- to 8.9-kb segments on the 3′ end of the genome. FECV/FIPV pairs from the same catteries or shelters were 97.3–99.5% related but were genetically distinct from FIPV and FECV strains obtained from cats living in geographically distinct environments. The high genetic similarity between FECVs and FIPVs from the same environment strongly suggested a common ancestry. Based on the presence of deletion mutations in the FIPVs and not in the FECVs, it was concluded that FIPVs evolved as mutants of FECVs. The mutations are deletions in the FIPVs and not insertions in the FECVs since similar sequences are present in other strains that have segregated earlier from a common ancestor. Therefore, the order of descent is from FECV to FIPV. Mutations unique to FIPVs were found in open reading frames (ORFs) 3c in 4 of 6 isolates and/or 7b in 3 of 6 isolates. When the study was extended to include 7 additional FIPV isolates, 11/13 of the FIPVs sequenced were found to have mutated 3c ORFs.


docid: ajbgreri

title: Sample-to-result molecular infectious disease assays: clinical implications, limitations and potential

text: Molecular infectious disease diagnostic tests have undergone major advances in the past decade and will continue to rapidly evolve. Assays have become extraordinarily simple to perform, eliminating the need for pre-analytic sample preparation and post-amplification analysis. This allows these tests to be performed in settings without sophisticated expertise in molecular biology, including locations with limited resources. Additionally, the sensitivity and specificity of these assays is superb and many offer extremely fast turn-around times. These tests have major impacts on patient care, but also have some limitations.


title: Synthesis of 3-fluoro-6-S-(2-S-pyridyl) nucleosides as potential lead cytostatic agents

text: Abstract The 3-deoxy-3-fluoro-6-S-(2-S-pyridyl)-6-thio-β-d-glucopyranosyl nucleoside analogs 7 were prepared via two facile synthetic routes. Their precursors, 3-fluoro-6-thio-glucopyranosyl nucleosides 5a-e, were obtained by the sequence of deacetylation of 3-deoxy-3-fluoro-β-d-glucopyranosyl nucleosides 2a-e, selective tosylation of the primary OH of 3 and finally treatment with potassium thioacetate. The desired thiolpyridine protected analogs 7a-c,f,g were obtained by the sequence of deacetylation of 5a-c followed by thiopyridinylation and/or condensation of the corresponding heterocyclic bases with the newly synthesized peracetylated 6-S-(2-S-pyridyl) sugar precursor 13, which was obtained via a novel synthetic route from glycosyl donor 12. None of the compounds 6 and 7 showed antiviral activity, but the 5-fluorouracil derivative 7c and particularly the uracil derivative 7b were endowed with an interesting and selective cytostatic action against a variety of murine and human tumor cell cultures.


Severe viral infection and the kidney: lessons learned from the H1N1 pandemic


title: Molecular Evolution and Structural Mapping of N-Terminal Domain in Spike Gene of Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

text: The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a lethal zoonotic pathogen circulating in the Arabian Peninsula since 2012. There is no vaccine for MERS and anti-viral treatment is generally not applicable. We investigated the evolution of the MERS-CoV spike gene sequences and changes in viral loads over time from patients in Saudi Arabia from 2015–2017. All the MERS-CoV strains belonged to lineage 5, and showed high sequence homology (99.9%) to 2017 strains. Recombination analysis showed a potential recombination event in study strains from patients in Saudi Arabia. The spike gene showed eight amino acid substitutions, especially between the A1 and B5 lineage, and contained positively selected codon 1020. We also determined that the viral loads were significantly (p < 0.001) higher in fatal cases, and virus shedding was prolonged in some fatal cases beyond 21 days. The viral concentration peaked during the first week of illness, and the lower respiratory specimens had higher levels of MERS-CoV RNA. The presence of the diversifying selection and the topologies with the structural mapping of residues under purifying selection suggested that codon 1020 might have a role in the evolution of spike gene during the divergence of different lineages. This study will improve our understanding of the evolution of MERS-CoV, and also highlights the need for enhanced surveillance in humans and dromedaries. The presence of amino acid changes at the N-terminal domain and structural mapping of residues under positive selection at heptad repeat 1 provides better insight into the adaptive evolution of the spike gene and might have a potential role in virus-host tropism and pathogenesis.


title: Major factors affecting the emergence and re-emergence of infectious diseases

text: The diversity of infectious disease threats currently facing humanity is unprecedented because of the remarkable emergence and reemergence of pathogens worldwide. Because of population mobility, globalization of commerce and the food supply, and the effects of the HIV/AIDS pandemic, infections in the developing world must be addressed to prevent infections in industrialized countries. Because pathogens do not recognize national boundaries, the rapidity with which individuals can circumnavigate the globe incubating infections makes the control of communicable diseases an enormous challenge for governments as well as for the public and primary health care systems. A global strategy for dealing with infectious disease threats must be developed and implemented as soon as possible.


title: Implementation of Clinical Diagnostic Criteria and Universal Symptom Survey Contributed to Lower Magnitude and Faster Resolution of the COVID-19 Epidemic in Wuhan

text: Abstract The majority of cases infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China centered in the city of Wuhan. Despite a rapid increase in the number of cases and deaths due to the coronavirus disease 2019 (COVID-19), the epidemic was stemmed via a combination of epidemic mitigation and control measures. This study evaluates how the implementation of clinical diagnostics and universal symptom surveys contributed to epidemic control in Wuhan. We extended the susceptibles-exposed-infectious-removed (SEIR) transmission dynamics model by considering three quarantined compartments (SEIR+Q). The SEIR+Q dynamics model was fitted using the daily reported number of confirmed infections and unconfirmed cases by clinical diagnostic criteria up to February 14, 2020 in Wuhan. Applying the model to carry forward the pre-February 14 trend in Wuhan, the number of daily new diagnosed cases would be expected to drop below 100 by March 25, below 10 by April 29, and reach 0 by May 31, 2020. The observed case counts after February 14 demonstrated that the daily new cases fell below 100 by March 6, below 10 by March 11, and reached 0 by March 18, or, respectively, 19, 49, and 74 d earlier than model predictions. By March 30, the observed number of cumulative confirmed cases was 50 006, which was 19 951 cases fewer than the predicted count. Effective reproductive number R(t) analysis using observed frequencies showed a remarkable decline after the implementation of clinical diagnostic criteria and universal symptom surveys, which was significantly below the R(t) curve estimated by the model assuming that the pre-February 14 trend was carried forward. In conclusion, the proposed SEIR+Q dynamics model was a good fit for the epidemic data in Wuhan and explained the large increase in the number of infections during February 12–14, 2020. The implementation of clinical diagnostic criteria and universal symptom surveys contributed to a contraction in both the magnitude and the duration of the epidemic in Wuhan.


Síndrome post-cuidados intensivos después de la pandemia por SARS-CoV-2


title: Rapid and visual detection of novel astroviruses causing fatal gout in goslings using one-step reverse transcription loop-mediated isothermal amplification

text: Abstract To visually and rapidly detect a novel goose astrovirus (N-GoAstV) causing fatal gout in goslings, an isothermal detection method based on one-step reverse transcription loop-mediated isothermal amplification (one-step RT-LAMP) was established. The one-step RT-LAMP assay for N-GoAstV detection, using Bst 3.0 DNA polymerase with strong reverse transcription activity and primer sets targeting the opening reading frame 1b (ORF1b) of N-GoAstV, could be completed in 30 min using a water bath at 61°C; the detection results could be visually observed by adding a pH-sensitive dye containing phenol red and cresol red. The detection limit of the one-step RT-LAMP assay was 57.8 copies/μL, which was similar to that of reverse transcription–quantitative polymerase chain reaction. The assay specifically detected N-GoAstV without any cross-reaction with other reference viruses, and this was further confirmed using enzyme digestion. These results indicated that the newly established RT-LAMP assay could accomplish reverse transcription, amplification, and visual result determination in one step, and the results obtained via this rapid and cost-effective method could be used to support disease control on farms in terms of N-GoAstV infection.


title: Determinants of the infection rate of the COVID-19 in the U.S. using ANFIS and virus optimization algorithm (VOA)

text: Recently, anovel coronavirus virus disease (COVID-19) has become a serious concern for global public health hazards. Infectious disease outbreaks such as COVID-19can also significantly affect the sustainable development of urban areas. Several factors such as population density and climatology parameters could potentially affect the spread of the COVID-19. In this study, a combination of the virus optimization algorithm (VOA) and adaptive network-based fuzzy inference system (ANFIS) to investigate the effects of various climate-related factors and population density on the spread of the COVID-19. For this purpose, data on the climate-related factors and the confirmed infected cases by the COVID-19across the U.S counties was used.The results show that the variable defined for the population density had the most significant impact on the performance of the developed models, which is an indication of the importance social distancing in reducing the infection rate and spread rate of the COVID-19. Among the climatology parameters, an increase in the maximum temperature was found to reduce the infection rate. Average temperature, minimum temperature, precipitation, and average wind speed were not found to significantly affect the spread of the COVID-19 while an increase in the relative humidity was found to slightly increase the infection rate. The findings of this research show that it could be expected to have reduced infection rate over the summer season. However, it should be noted that the models developed in this study were based on limited one-month data. Future investigation can benefit from using more comprehensive data covering a wider range for the input variables.


Maladies respiratoires, allergies et infections à COVID-19. Premières nouvelles de Wuhan


title: Pharmacological and Biological Antiviral Therapeutics for Cardiac Coxsackievirus Infections

text: Subtype B coxsackieviruses (CVB) represent the most commonly identified infectious agents associated with acute and chronic myocarditis, with CVB3 being the most common variant. Damage to the heart is induced both directly by virally mediated cell destruction and indirectly due to the immune and autoimmune processes reacting to virus infection. This review addresses antiviral therapeutics for cardiac coxsackievirus infections discovered over the last 25 years. One group represents pharmacologically active low molecular weight substances that inhibit virus uptake by binding to the virus capsid (e.g., pleconaril) or inactivate viral proteins (e.g., NO-metoprolol and ribavirin) or inhibit cellular proteins which are essential for viral replication (e.g., ubiquitination inhibitors). A second important group of substances are interferons. They have antiviral but also immunomodulating activities. The third and most recently discovered group includes biological and cellular therapeutics. Soluble receptor analogues (e.g., sCAR-Fc) bind to the virus capsid and block virus uptake. Small interfering RNAs, short hairpin RNAs and antisense oligonucleotides bind to and led to degradation of the viral RNA genome or cellular RNAs, thereby preventing their translation and viral replication. Most recently mesenchymal stem cell transplantation has been shown to possess antiviral activity in CVB3 infections. Taken together, a number of antiviral therapeutics has been developed for the treatment of myocardial CVB infection in recent years. In addition to low molecular weight inhibitors, biological therapeutics have become promising anti-viral agents.


title: A political economy perspective on horizontal FDI in a dynamic Cournot-oligopoly with endogenous entry

text: Abstract Entry in a homogeneous Cournot-oligopoly is excessive if and only if there is business-stealing (Amir et al., 2014). The excessive entry prediction has been derived primarily for closed economies and using a welfarist benchmark. We extend this framework and allow for (1) horizontal FDI in a multi-period setting and (2) interest group-based government behaviour. Opening the market to greenfield investments from abroad tends to aggravate the entry distortion. Moreover, market opening may reduce welfare if a more pronounced entry distortion dominates the gain in consumer surplus. Finally, a government, which places sufficiently little weight on the interests of consumers, will object to market opening, even if welfare rises.


title: Structure and infrastructure of infectious agent research literature: SARS

text: Text mining was used to extract technical intelligence from the open source global SARS research literature. A SARS-focused query was applied to the Science Citation Index (SCI) (SCI 2008) database for the period 1998–early 2008. The SARS research literature infrastructure (prolific authors, key journals/institutions/countries, most cited authors/journals/documents) was obtained using bibliometrics, and the SARS research literature technical structure (hierarchical taxonomy) was obtained using computational linguistics/document clustering.


title: Structural changes in foreign investors’ trading behavior and the corresponding impact on Taiwan's stock market

text: Abstract This study investigates the impact of the expected and unexpected trading behavior of foreign investors on return volatilities during structural change periods. And the jump intensity model pinpoints crucial events that have influenced the stock market. The empirical results find that there has been a stabilizing effect of foreign investment on Taiwan's stock market as restrictions on foreign trading have been gradually relaxed, as opposed to there being a complete relaxation of the restrictions imposed on Qualified Foreign Institutional Investors (QFIIs).


title: Benefits of using heterologous polyclonal antibodies and potential applications to new and undertreated infectious pathogens

text: BACKGROUND: Passive immunotherapy using polyclonal antibodies (immunoglobulins) has been used for over a century in the treatment and post-exposure prophylaxis of various infections and toxins. Heterologous polyclonal antibodies are obtained from animals hyperimmunised with a pathogen or toxin. AIMS: The aims of this review are to examine the history of animal polyclonal antibody therapy use, their development into safe and effective products and the potential application to humans for emerging and neglected infectious diseases. METHODS: A literature search of OVID Medline and OVID Embase databases was undertaken to identify articles on the safety, efficacy and ongoing development of polyclonal antibodies. The search contained database-specific MeSH and EMTREE terms in combination with pertinent text-words: polyclonal antibodies and rare/neglected diseases, antivenins, immunoglobulins, serum sickness, anaphylaxis, drug safety, post marketing surveillance, rabies, human influenza, Dengue, West Nile, Nipah, Hendra, Marburg, MERS, Hemorrhagic Fever Virus, and Crimean-Congo. No language limits were applied. The final search was completed on 20.06.2015. Of 1960 articles, title searches excluded many irrelevant articles, yielding 303 articles read in full. Of these, 179 are referenced in this study. RESULTS: Serum therapy was first used in the 1890s against diphtheria. Early preparation techniques yielded products contaminated with reactogenic animal proteins. The introduction of enzymatic digestion, and purification techniques substantially improved their safety profile. The removal of the Fc fragment of antibodies further reduces hypersensitivity reactions. Clinical studies have demonstrated the efficacy of polyclonal antibodies against various infections, toxins and venoms. Products are being developed against infections for which prophylactic and therapeutic options are currently limited, such as avian influenza, Ebola and other zoonotic viruses. CONCLUSIONS: Polyclonal antibodies have been successfully applied to rabies, envenomation and intoxication. Polyclonal production provides an exciting opportunity to revolutionise the prognosis of both longstanding neglected tropical diseases as well as emerging infectious threats to humans.


title: Safety of intranasal corticosteroids in acute rhinosinusitis

text: Treatment guidelines for acute rhinosinusitis (RS) recommend the use of intranasal corticosteroids (INSs) as monotherapy or adjunctive therapy. However, the adverse event (AE) profiles of oral glucocorticoids, which result largely from the systemic absorption of those agents, have engendered concerns about the safety of INSs. These concerns persist for INSs despite significant or marked clinical differences between them and systemic corticosteroids in systemic absorption and among the INSs in bioavailability, mechanism of action, and lipophilicity, which may contribute to differences in AEs. For example, the systemic bioavailability of the INSs as a percentage of the administered drug is less than 0.1% for mometasone furoate, less than 1% for fluticasone propionate, 46% for triamcinolone acetonide, and 44% for beclomethasone dipropionate. A review of the safety profiles of INSs, as reported in clinical trials in acute and chronic RS and allergic rhinitis, shows primarily local AEs (eg, epistaxis and headache) that are generally classified as mild to moderate, with occurrence rates that are similar to those with placebo. Studies of the safety of mometasone furoate, fluticasone propionate, budesonide, and triamcinolone acetonide did not identify any evidence of systemic AEs, such as growth retardation in children due to suppression of the hypothalamic-pituitary-adrenal axis, bone mineral density loss, or cataracts, which suggests that INSs can be safely administered in patients with acute RS without concern for systemic AEs.


docid: aiksdnjc

title: Mobile populations across the Mediterranean Sea and beyond: travel medicine, mass gathering medicine and homeless health

text: The Méditerranée Infection institute is internationally recognized for its expertise in infectious diseases and tropical medicine, and is one of the most active research centres for infectious diseases in Europe. Surveillance and research addressing infectious diseases in globally mobile populations is one of the strong components of the research conducted at the institute. A significant amount of clinical, microbiologic and epidemiologic works have been conducted in international travellers, pilgrims participating in large international religious gatherings, economic migrants and homeless migrant people over the last decades by our group. Our strong anchoring in several countries around the Mediterranean Sea and beyond, as well as the pivotal role of Marseille in the EuroTravNet and GeoSentinel international networks that monitor travel-associated diseases, reinforce our leading position in the fields of travel and tropical medicine, mass gathering medicine and homeless health.


title: CytoResc – “CytoSorb” Rescue for critically ill patients undergoing the COVID-19 Cytokine Storm: A structured summary of a study protocol for a randomized controlled trial

text: OBJECTIVES: Approximately 8 - 10 % of COVID-19 patients present with a serious clinical course and need for hospitalization, 8% of hospitalized patients need ICU-treatment. Currently, no causal therapy is available and treatment is purely supportive. The main reason for death in critically ill patients is acute respiratory failure. However, in a number of patients a severe hyperinflammatory response with excessively elevated proinflammatory cytokines causes vasoplegic shock resistant to vasopressor therapy. A new polystyrene-based hemoadsorber (CytoSorb®, Cytosorbents Inc., New Jersey, USA) has been shown to adsorb effectively cytokines and other middle molecular weight toxins this way reducing their blood concentrations. This has been routinely used in clinical practice in the EU for other conditions where a cytokine storm occurs and an observational study has just been completed on COVID-19 patients. We hypothesized that the extracorporeal elimination of cytokines in critically ill COVID-19 patients with suspected hyperinflammation and shock may stabilize hemodynamics and improve outcome. The primary endpoint is time until resolution of vasoplegic shock, which is a well implemented, clinically relevant endpoint in critical care studies. TRIAL DESIGN: Phase IIb, multicenter, prospective, open-label, randomized, 1:1 parallel group pilot study comparing the additional use of “CytoSorb” to standard of care without “CytoSorb”. PARTICIPANTS: Patients are recruited from the Intensive Care Units (ICUs) of 7 participating centers in Germany (approximately 10 ICUs). All patients aged 18- 80 with positive polymerase chain reaction (PCR) test for SARS-CoV-2, a C-reactive protein (CRP) ≥ 100 mg/l, a Procalcitonin (PCT) < 2 ng/l, and suspected cytokine storm defined via a vasoplegic shock (Norepinephrine > 0.2 μg/min/kg to achieve a Mean Arterial Pressure ≥ 65mmHg). Patients are included irrespective of indication for renal replacement therapy. Suspected or proven bacterial cause for vasoplegic shock is a contraindication. INTERVENTION AND COMPARATOR: Within 24 hours after meeting the inclusion criteria patients will be randomized to receive either standard of care or standard of care and additional “CytoSorb” therapy via a shaldon catheter for 3-7 days. Filter exchange is done every 24 hours. If patients receive antibiotics, an additional dose of antibiotics is administered after each change of “CytoSorb” filter in order to prevent underdosing due to “CytoSorb” treatment. MAIN OUTCOMES: Primary outcome is time to resolution of vasoplegic shock (defined as no need for vasopressors for at least 8 hours in order to sustain a MAP ≥ 65mmHg) in days. Secondary outcomes are 7 day mortality after fulfilling the inclusion criteria, mortality until hospital discharge, Interleukin-6 (IL-6) measurement on day 1 and 3, need for mechanical ventilation, duration of mechanical ventilation, duration of ICU-stay, catecholamine dose on day 1/2/3 after start of “CytoSorb” and acute kidney injury. RANDOMIZATION: An electronic randomization will be performed using the study software secuTrial® administered by the Clinical Study Center (CSC) of the Charité – Universitätsmedizin Berlin, Germany. Randomization is done in blocks by 4 stratified by including center. BLINDING (MASKING): The trial will be non-blinded for the clinicians and patients. The statistician will receive a blinded data set, so that all analyses will be conducted blinded. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): As this is a pilot study with the goal to examine the feasibility of the study design as well as the intervention effect, no formal sample size calculation was conducted. A total number of approximately 80-100 patients is planned (40-50 patients per group). Safety assessment is done after the inclusion of each 10 patients per randomization group. TRIAL STATUS: Please see the study protocol version from April 24 2020. Recruitment of patients is still pending. TRIAL REGISTRATION: The study was registered on April 27 2020 in the German Registry of Clinical Trials (DRKS) under the number DRKS00021447. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


title: Chapter 9 Nutrition and feeding of dairy cattle

text: Abstract Feeding dairy cattle utilize the sciences of nutrition, biochemistry, and microbiology and combine them with animal husbandry. In this chapter, we will discuss the nutrients and how they are integral for dairy cattle performance (growth and milk production). We will evaluate the feeding of calves and heifers along with some brief practical feeding recommendations for dry and prepartum cows.


title: Les gastroenterites virales

text: Summary Many virus are able to induce gastroenteritis, especially in young children with immunological or nutritional defects. The most frequently observed, using ELISA, are Rotavirus. The others : Norwalk agent, Coronavirus, Breda virus, are identified using electron microscope. Using symptomatic therapy, prognosis is related to precocious hydratation.


title: Molecular Pathogenesis of Middle East Respiratory Syndrome (MERS) Coronavirus

text: PURPOSE OF REVIEW: Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 and is listed in the World Health Organization’s blueprint of priority diseases that need immediate research. Camels are reservoirs of this virus, and the virus spills over into humans through direct contact with camels. Human-to-human transmission and travel-associated cases have been identified as well. Limited studies have characterized the molecular pathogenesis of MERS-CoV. Most studies have used ectopic expression of viral proteins to characterize MERS-CoV and its ability to modulate antiviral responses in human cells. Studies with live virus are limited, largely due to the requirement of high containment laboratories. In this review, we have summarized current studies on MERS-CoV molecular pathogenesis and have mentioned some recent strategies that are being developed to control MERS-CoV infection. RECENT FINDINGS: Multiple antiviral molecules with the potential to inhibit MERS-CoV infection by disrupting virus-receptor interactions are being developed and tested. Although human vaccine candidates are still being developed, a candidate camel vaccine is being tested for efficacy. Combination of supportive treatment with interferon and antivirals is also being explored. SUMMARY: New antiviral molecules that inhibit MERS-CoV and host cell receptor interaction may become available in the future. Additional studies are required to identify and characterize the pathogenesis of MERS-CoV EMC/2012 and other circulating strains. An effective MERS-CoV vaccine, for humans and/or camels, along with an efficient combination antiviral therapy may help us prevent future MERS cases.


title: The damage-response framework of microbial pathogenesis

text: The late twentieth century witnessed the emergence of numerous infectious diseases that are caused by microorganisms that rarely cause disease in normal, healthy immunocompetent hosts. The emergence of these diseases shows that the existing concepts of pathogenicity and virulence do not take into account the fact that both the microorganism and the host contribute to microbial pathogenesis. To address this impediment to studies of host–microorganism interactions, we propose a new theoretical approach to understanding microbial pathogenesis, known as the 'damage-response' framework.


title: Protecting Chinese healthcare workers while combating the 2019 novel coronavirus

text: Hospital-associated transmission is an important route of spreading the 2019 novel coronavirus (2019-nCoV) infection and pneumonia (Corona Virus Disease 2019, COVID-19) [1]. Healthcare workers (HCWs) are at high risk while combating COVID-19 at the very frontline, and nosocomial outbreaks among HCWs are not unusual in similar settings; the 2003 severe acute respiratory syndrome (SARS) outbreak led to over 966 HCW infections with 1.4% deaths in mainland China [2]. As of 11 February 2020, 3019 HCWs might have been infected with 2019-nCov in China, 1716 HCW cases were confirmed by nucleic acid testing[3], and at least 6 HCWs died, including the famous whistleblower Dr Li Wenliang. In view of this severe situation, we are recommending urgent interventions to help to protect HCWs.


title: UPPER RESPIRATORY TRACT INFECTION

text: Upper respiratory tract infection (URI) is a general term for a heterogeneous group of illnesses caused by numerous etiologic agents that affect the mucosal lining of the upper respiratory tract, including the middle-ear cavity and paranasal sinuses. URIs are primarily caused by viruses, rhinoviruses being the most common etiological agents. Respiratory viruses transmit easily via direct contact or aerosols. The incidence of URI is highest in children who suffer 6–8 infections per year. The main symptoms of URI are nasal blockage and discharge, sneezing, sore throat, and cough. Fever occurs variably, most commonly in children. Viral URIs often predispose to bacterial complications. Acute otitis media is the most common complication in children, whereas sinusitis and pneumonia are more frequent in adults and the elderly. The treatment of URI is mainly symptomatic because specific antivirals are available only for influenza viruses. Antibiotics have no efficacy for viral URI but are commonly used for treating acute otitis media and sinusitis. Most URIs are self-limited illnesses with an average duration of 7–10 days and an excellent prognosis.


title: Are we prepared? The development of performance indicators for public health emergency preparedness using a modified Delphi approach

text: BACKGROUND: Disasters and emergencies from infectious diseases, extreme weather and anthropogenic events are increasingly common. While risks vary for different communities, disaster and emergency preparedness is recognized as essential for all nation-states. Evidence to inform measurement of preparedness is lacking. The objective of this study was to identify and define a set of public health emergency preparedness (PHEP) indicators to advance performance measurement for local/regional public health agencies. METHODS: A three-round modified Delphi technique was employed to develop indicators for PHEP. The study was conducted in Canada with a national panel of 33 experts and completed in 2018. A list of indicators was derived from the literature. Indicators were rated by importance and actionability until achieving consensus. RESULTS: The scoping review resulted in 62 indicators being included for rating by the panel. Panel feedback provided refinements to indicators and suggestions for new indicators. In total, 76 indicators were proposed for rating across all three rounds; of these, 67 were considered to be important and actionable PHEP indicators. CONCLUSIONS: This study developed an indicator set of 67 PHEP indicators, aligned with a PHEP framework for resilience. The 67 indicators represent important and actionable dimensions of PHEP practice in Canada that can be used by local/regional public health agencies and validated in other jurisdictions to assess readiness and measure improvement in their critical role of protecting community health.


title: Vanadium compounds in medicine

text: Abstract Vanadium is a transition metal that, being ubiquitously distributed in soil, crude oil, water and air, also found roles in biological systems and is an essential element in most living beings. There are also several groups of organisms which accumulate vanadium, employing it in their biological processes. Vanadium being a biological relevant element, it is not surprising that many vanadium based therapeutic drugs have been proposed for the treatment of several types of diseases. Namely, vanadium compounds, in particular organic derivatives, have been proposed for the treatment of diabetes, of cancer and of diseases caused by parasites. In this work we review the medicinal applications proposed for vanadium compounds with particular emphasis on the more recent publications. In cells, partly due to the similarity of vanadate and phosphate, vanadium compounds activate numerous signaling pathways and transcription factors; this by itself potentiates application of vanadium-based therapeutics. Nevertheless, this non-specific bio-activity may also introduce several deleterious side effects as in addition, due to Fenton's type reactions or of the reaction with atmospheric O2, VCs may also generate reactive oxygen species, thereby introducing oxidative stress with consequences presently not well evaluated, particularly for long-term administration of vanadium to humans. Notwithstanding, the potential of vanadium compounds to treat type 2 diabetes is still an open question and therapies using vanadium compounds for e.g. antitumor and anti-parasitic related diseases remain promising.


title: Discovery of Novel Alphacoronaviruses in European Rodents and Shrews

text: Eight hundred and thirteen European rodents and shrews encompassing seven different species were screened for alphacoronaviruses using PCR detection. Novel alphacoronaviruses were detected in the species Rattus norvegicus, Microtus agrestis, Sorex araneus and Myodes glareolus. These, together with the recently described Lucheng virus found in China, form a distinct rodent/shrew-specific clade within the coronavirus phylogeny. Across a highly conserved region of the viral polymerase gene, the new members of this clade were up to 22% dissimilar at the nucleotide level to the previously described Lucheng virus. As such they might represent distinct species of alphacoronaviruses. These data greatly extend our knowledge of wildlife reservoirs of alphacoronaviruses.


title: Immune responses in Balb/c mice induced by a candidate SARS-CoV inactivated vaccine prepared from F69 strain

text: The immunogenicity of a candidate-inactivated vaccine prepared from SARS-CoV F69 strain was evaluated in Balb/c mice. Potent humoral immune responses were induced under the elicitation of three times of immunizations at 2-week intervals with this vaccine, combined with three types of adjuvants (Freund's adjuvant, Al(OH)(3) adjuvant and CpG adjuvant). Titers of specific IgG antibodies in three test groups all peaked in the sixth week after first vaccination, but significant differences existed in the kinetics of specific IgG antibody levels. The strong neutralizing capacity exhibited in micro-cytopathic effect neutralization tests indicated the specific antibodies are protective. Western blot assay further demonstrated the specificity of the induced serum antibodies.


title: Microwave-induced release and degradation of airborne endotoxins from Escherichia coli bioaerosol

text: Abstract Endotoxins are widely distributed toxins in the outer cell-wall membranes of Gram-negative bacteria and other microorganisms. Chronic exposure to endotoxins can induce and exacerbate airway symptoms and diseases. However, the release and degradation of airborne endotoxins from bioaerosol by microwave (MW) irradiation have not yet been reported. This study investigated the distribution and fate of airborne endotoxins during MW irradiation process, as well as the kinetics and thermodynamics of the degradation of airborne endotoxins. Results showed that MW irradiation induced cell lysis, thus considerably increasing the proportion of cells with ruptured membranes. Furthermore, MW irradiation changed the distribution of airborne endotoxins, sharply decreased the concentration of bound endotoxins from 230 EU/m3 to 68 EU/m3, and increased the concentration of free endotoxins from 21 EU/m3 to 122 EU/m3. These results indicated that MW irradiation released endotoxins from cells into the atmosphere. MW irradiation likely degraded endotoxins by exerting thermal effects, which achieved a total endotoxin removal efficiency of as high as 35%. Endotoxin degradation was a first-order reaction and required the activation energy of 26.3 kJ/mol.


title: Coronavirus disease 2019 (COVID-19) in pregnant women: A report based on 116 cases

text: Abstract Background The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global public health emergency. Data on the effect of COVID-19 in pregnancy are limited to small case series. Objectives To evaluate the clinical characteristics and outcomes in pregnancy and the vertical transmission potential of SARS-CoV-2 infection. Study Desigh Clinical records were retrospectively reviewed for 116 pregnant women with COVID-19 pneumonia from 25 hospitals in China between January 20 and March 24, 2020. Evidence of vertical transmission was assessed by testing for SARS-CoV-2 in amniotic fluid, cord blood, and neonatal pharyngeal swab samples. Results The median gestational age on admission was 38+0 (IQR 36+0-39+1) weeks. The most common symptoms were fever (50.9%, 59/116) and cough (28.4%, 33/116); 23.3% (27/116) patients presented without symptoms. Abnormal radiologic findings were found in 96.3% (104/108) of cases. There were eight cases (6.9%, 8/116) of severe pneumonia but no maternal deaths. One of eight patients (1/8) that presented in the first- and early-second-trimester had a missed spontaneous abortion. Twenty-one of 99 patients (21.2%, 21/99) that had delivered had preterm birth, including six with preterm premature ruptured of membranes. The rate of spontaneous preterm birth before 37 weeks was 6.1% (6/99). There was one case of severe neonatal asphyxia that resulted in neonatal death. Eighty-six of the 100 neonates that had testing for SARS-CoV-2 had negative results, of these ten neonates had paired amniotic fluid and cord blood samples that were tested negative for SARS-CoV-2. Conclusions SARS-CoV-2 infection during pregnancy is not associated with an increased risk of spontaneous abortion and spontaneous preterm birth. There is no evidence of vertical transmission of SARS-CoV-2 infection when the infection manifests during the third-trimester of pregnancy.


title: A review of big data and medical research

text: Universally, the volume of data has increased, with the collection rate doubling every 40 months, since the 1980s. “Big data” is a term that was introduced in the 1990s to include data sets too large to be used with common software. Medicine is a major field predicted to increase the use of big data in 2025. Big data in medicine may be used by commercial, academic, government, and public sectors. It includes biologic, biometric, and electronic health data. Examples of biologic data include biobanks; biometric data may have individual wellness data from devices; electronic health data include the medical record; and other data demographics and images. Big data has also contributed to the changes in the research methodology. Changes in the clinical research paradigm has been fueled by large-scale biological data harvesting (biobanks), which is developed, analyzed, and managed by cheaper computing technology (big data), supported by greater flexibility in study design (real-world data) and the relationships between industry, government regulators, and academics. Cultural changes along with easy access to information via the Internet facilitate ease of participation by more people. Current needs demand quick answers which may be supplied by big data, biobanks, and changes in flexibility in study design. Big data can reveal health patterns, and promises to provide solutions that have previously been out of society’s grasp; however, the murkiness of international laws, questions of data ownership, public ignorance, and privacy and security concerns are slowing down the progress that could otherwise be achieved by the use of big data. The goal of this descriptive review is to create awareness of the ramifications for big data and to encourage readers that this trend is positive and will likely lead to better clinical solutions, but, caution must be exercised to reduce harm.


title: Comparative transcriptome analysis reveals induction of apoptosis in chicken kidney cells associated with the virulence of nephropathogenic infectious bronchitis virus

text: Abstract Avian infectious bronchitis virus (IBV) that causes respiratory and nephritic diseases in chicken is a major poultry pathogen leading to serious economic loss worldwide. The nephropathogenic IBV strains cause nephritis and kidney lesions intrinsically and the pathogenic mechanism is still unclear. In the present study, SPF chicks were infected with three nephropathogenic IBVs of different virulence and their gene expression profiles in chicken kidney were compared at transcriptome level. As a result, 1279 differentially expressed (DE) genes were found in very virulent SCDY2 inoculated group, 145 in virulent SCK2 group and 74 in non-virulent LDT3-A group when compared to mock infected group. Gene Ontology (GO) and KEGG pathway enrichment analysis on SCDY2 group displayed that the up-regulated DE genes were mainly involved in cell apoptosis, and the down-regulated genes were involved in metabolic processes and DNA replication. Protein-Protein Interaction (PPI) analysis showed that DE genes in SCDY2 group formed a network, and the core of the network was composed by cell apoptosis and immune response proteins. The clustering of gene expression profile among the three virus inoculated groups indicated that the majority of up-regulated DE genes on apoptosis in very virulent SCDY2 group were up-regulated more or less in virulent SCK2 group and those down-regulated on innate immune response in SCDY2 group were also down-regulated differently in SCK2 group. In addition, the number of apoptotic cells detected experimentally in kidney tissue were very different among the three virus inoculated groups and were positively accordant with the viral titer, kidney lesions and viral virulence of each group. Taken all together, the present study revealed that virulent nephropathogenic IBV infection modified a number of gene expression and induction of apoptosis in kidney cells may be a major pathogenic determinant for virulent nephropathogenic IBV.


The association of hypertension with the severity and mortality of COVID-19 patients: evidence based on adjusted effect estimates


title: The action of three antiseptics/disinfectants against enveloped and non-enveloped viruses

text: Abstract The antiviral action of chloroxylenol, benzalkonium chloride and cetrimide/chlorhexidine was assessed against a range of enveloped and non-enveloped human viruses using a suspension test method. Viral suspensions of 106–107 pfu/TCID50 or sfu were prepared in each of the antiseptic/ disinfectant solutions in the presence of a bovine serum/yeast extract mixture to simulate ‘dirty conditions’. During incubation, aliquots were removed at predetermined timepoints up to 10 min to assess the kinetics of inactivation. Results indicate that all products were effective in inactivating the enveloped viruses herpes simplex virus type 1 and human immunodeficiency virus type 1, whilst being ineffective in inactivating human coronavirus, also enveloped, and the non-enveloped viruses. The exception to this was the benzalkonium chloride-based product (Dettol Hospital Concentrate) which was active against the non-enveloped human coxsackie virus. Four antiseptic/disinfectant solutions with chloroxylenol, benzalkonium chloride, cetrimide/ chlorhexidme and povidone-iodine were also assessed for antiviral effect against human immunodeficiency virus in the presence of whole human blood. All four solutions proved to be effective within l min despite the cytotoxic nature of the compounds to the detection system.


title: CHILBLAIN-LIKE ACRAL LESIONS DURING THE COVID-19 PANDEMIC (“COVID TOES”): HISTOLOGIC, IMMUNOFLUORESCENCE AND IMMUNOHISTOCHEMICAL STUDY OF 17 CASES

text: Abstract Background During the COVID-19 pandemic, several acral chilblain-like skin lesions (CBLL) were observed in young patients with suspected, but mostly unconfirmed, infection with SARS-CoV-2. The histopathological aspect of these lesions is as yet poorly known. Objective To investigate the pathologic features of CBLL. Methods Biopsies were obtained from 17 cases of CBLL during the COVID-19 pandemic in France and were studied by routine histological examination, immunohistochemistry and direct immunofluorescence (DIF). The patients had suspected but unconfirmed infection with SARS-CoV-2 (negative nasopharyngeal PCR test and serological tests). Results CBLL showed many features with those reported in idiopathic (IC) and auto-immune related chilblains (AC), including epidermal necrotic keratinocytes, dermal edema, perivascular and perieccrine sweat gland lymphocytic (predominantly CD3/CD4+) inflammation and frequent vascular changes (endothelialitis, microthromboses, fibrin deposition, immunoreactant deposits on vessels). Conclusions CBLL show similar histopathologic features with IC and AC, with a rather high rate of vascular changes and DIF positivity. The role of SARS-CoV-2 in the development of these puzzling lesions remains to be elucidated.


title: Assessment of SARS-CoV-2 serological tests for the diagnosis of COVID-19 through the evaluation of three immunoassays: two automated immunoassays (Euroimmun and Abbott) and one rapid lateral flow immunoassay (NG Biotech)

text: BACKGROUND: The emergence of new SARS-CoV-2 has promoted the development of new serological tests that could be complementary to RT-PCR. Nevertheless, the assessment of clinical performances of available tests is urgently required as their use has just been initiated for diagnose. OBJECTIVES: The aim of this study was to assess the performance of three immunoassays for the detection of SARS-CoV-2 antibodies. METHODS: Two automated immunoassays (Abbott SARS-CoV-2 CLIA IgG and Euroimmun Anti-SARS-CoV-2 ELISA IgG/IgA assays) and one lateral flow immunoassay (LFIA NG-Test® IgG-IgM COVID-19) were tested. 293 specimens were analyzed from patients with a positive RT-PCR response, from patients with symptoms consistent with COVID-19 but exhibiting a negative response to the RT-PCR detection test, and from control group specimens. Days since symptoms onset were collected from clinical information sheet associated with respiratory tract samples. RESULTS: Overall sensitivity for IgG was equivalent (around 80%) for CLIA, ELISA and LFIA. Sensitivity for IgG detection, >14 days after onset of symptoms, was 100.0% for all assays. Overall specificity for IgG was greater for CLIA and LFIA (more than 98%) compared to ELISA (95.8%). Specificity was significantly different between IgA ELISA (78.9%) and IgM LFIA (95.8%) (p < 0.05). The best agreement was observed between CLIA and LFIA assays (97%; k = 0.936). CONCLUSION: Excellent sensitivity for IgG detection was obtained >14 days after onset of symptoms for all immunoassays. Specificity was also excellent for IgG CLIA and IgG LFIA. Our study shows that NG-Test® is reliable and accurate for routine use in clinical laboratories.


Emerging Infectious Diseases in the Emergency Care Setting


title: Infectious Bronchitis Virus Infection Induces Apoptosis during Replication in Chicken Macrophage HD11 Cells

text: Avian infectious bronchitis has caused huge economic losses in the poultry industry. Previous studies have reported that infectious bronchitis virus (IBV) infection can produce cytopathic effects (CPE) and apoptosis in some mammalian cells and primary cells. However, there is little research on IBV-induced immune cell apoptosis. In this study, chicken macrophage HD11 cells were established as a cellular model that is permissive to IBV infection. Then, IBV-induced apoptosis was observed through a cell viability assay, morphological changes, and flow cytometry. The activity of caspases, the inhibitory efficacy of caspase-inhibitors and the expression of apoptotic genes further suggested the activation of apoptosis through both intrinsic and extrinsic pathways in IBV-infected HD11 cells. Additionally, ammonium chloride (NH(4)Cl) pretreated HD11 cells blocked IBV from entering cells and inhibited IBV-induced apoptosis. UV-inactivated IBV also lost the ability of apoptosis induction. IBV replication was increased by blocking caspase activation. This study presents a chicken macrophage cell line that will enable further analysis of IBV infection and offers novel insights into the mechanisms of IBV-induced apoptosis in immune cells.


title: Ovarian Tumor (OTU)-domain Containing Viral Proteases Evade Ubiquitin- and ISG15-dependent Innate Immune Responses

text: Ubiquitin (Ub) and interferon stimulated gene product 15 (ISG15) reversibly conjugate to proteins via a conserved LRLRGG C-terminal motif, mediating important innate antiviral responses. The ovarian tumor (OTU) domain represents a superfamily of predicted proteases found in eukaryotic, bacterial and viral proteins, some of which have Ub-deconjugating activity. We show that the OTU domain-containing proteases of nairoviruses and arteriviruses hydrolyze Ub and ISG15 from cellular target proteins. This broad activity contrasts with the target specificity of known mammalian OTU domain-containing proteins. The biological significance of this activity of viral OTU domain-containing proteases was evidenced by their capacity to inhibit NF-κB dependent signaling and to antagonize the antiviral effects of ISG15 during Sindbis virus infection in vivo. The deconjugating activity of viral OTU proteases represents a novel viral immune evasion mechanism that inhibits Ub-and ISG15-dependent antiviral pathways.


The Topic of COVID-19–Related Liver Injury Needs More Rigorous Research


docid: sstayqml

title: Respiratory Virus Infections in People Over 14 Years of Age in Poland in the Epidemic Season of 2017/18

text: People most at risk of influenza complications are the elderly with impaired immunity. Clinical picture of influenza virus infection includes symptoms such as chills, increased body temperature, dry cough, chest pain, or dizziness as well as headaches and muscle aches. In the diagnosis of influenza, quick and effective tests are necessary. Sensitive diagnostic methods of molecular biology require more time, but the result firmly confirm or exclude the presence of the genetic material of influenza or other respiratory viruses. Influenza vaccination plays an important role in combating influenza infection. Unfortunately, the awareness of vaccination benefits is insufficient in Poland. In this study we demonstrate the results of examination of 4,507 people aged over 14 years toward the influenza infection in the epidemic season of 2017/18. Most of the confirmed infections were reported in older people aged over 65, a high-risk population group. A low percentage of the vaccinated population may affect an increased number of confirmed influenza viruses in the elderly. The findings demonstrate a need to increase awareness of vaccination benefits, which is particularly essential to avoid influenza infection in the elderly.


title: A spatio-temporal analysis for exploring the effect of temperature on COVID-19 early evolution in Spain

text: Abstract The new SARS-CoV-2 coronavirus, which causes the COVID-19 disease, was reported in Wuhan, China, in December 2019. This new pathogen has spread rapidly around more than 200 countries, in which Spain has one of the world's highest mortality rates so far. Previous studies have supported an epidemiological hypothesis that weather conditions may affect the survival and spread of droplet-mediated viral diseases. However, some contradictory studies have also been reported in the same research line. In addition, many of these studies have been performed considering only meteorological factors, which can limit the reliability of the results. Herein, we report a spatio-temporal analysis for exploring the effect of daily temperature (mean, minimum and maximum) on the accumulated number of COVID-19 cases in the provinces of Spain. Non-meteorological factors such as population density, population by age, number of travellers and number of companies have also been considered for the analysis. No evidence suggesting a reduction in COVID-19 cases at warmer mean, minimum and maximum temperatures has been found. Nevertheless, these results need to be interpreted cautiously given the existing uncertainty about COVID-19 data, and should not be extrapolated to temperature ranges other than those analysed here for the early evolution period.


title: A signal-flexible gene diagnostic strategy coupling loop-mediated isothermal amplification with hybridization chain reaction

text: Abstract Recent study proves that the combination of loop mediated isothermal nucleic acid amplification (LAMP) with one-step strand displacement (OSD) is of great help to improve the sequence specificity during genetic detection. However, because OSD is incapable of signal amplification, the signal-to-noise ratio or the observable signal change may be usually not significant enough to satisfy practical usage. With the purpose to overcome this challenge, herein a more advanced and practical sensing principle is developed with the OSD replaced by an amplifiable nucleic acid circuit, hybridization chain reaction (HCR). The very contagious norovirus (NoV) was employed as the model target. Compared with LAMP-OSD, the LAMP-HCR can detect as few as 30 copies of NoV gene in 2% fecal samples with significantly enlarged signal change and signal-to-background ratio. Therefore, more reliable detection is achieved. Moreover, due to the high compatibility of HCR, the final LAMP-HCR products can be flexibly transduced into different types of readouts, including fluorescence, flow cytometer (FCM) and even a personal glucose meter (PGM). This further enlarges the operating environments for the detection from hospital labs, bedsides, to potential off-the-shelf devices in local pharmacies. Especially when using FCM or PGM, with the assistance of magnetic beads (MBs), the detection shows even higher tolerance capability to complicated biological matrices.


title: OTITIS MEDIA AGUDA. DIAGNÓSTICO Y MANEJO PRÁCTICO

text: RESUMEN La otitis media aguda es una patología infecciosa del oído medio muy frecuente. El diagnóstico es clínico, por lo que es fundamental un acucioso examen físico y una neumootoscopía para evaluar la movilidad timpánica. Hay dos tendencias respecto al manejo, tratamiento antibiótico inmediato u observación estricta (dependiendo de las características del paciente y del cuadro clínico). Los gérmenes más frecuentes son los virus, Neumococo, Haemophilus influenza y Moraxella catarrhalis. La prevalencia de cada uno de ellos varía según región geográfica y según la presencia de vacunación. La resistencia a antibióticos ha ido en aumento en estos años, pero aún puede considerarse sensible a amoxicilina por lo que se recomienda su uso como primera línea. En el caso de fracaso a tratamiento pueden utilizarse asociaciones con B-lactámicos y/o cefalosporinas, dejando en forma excepcional clindamicina o quinolonas. Aquellos niños con OMA recurrente requerirán evaluación por especialidad para mayor estudio y tratamiento. SUMMARY Acute otitis media is a very frequent cause of medical visit and antimicrobial use in children. Clinical diagnosis should be performed with pneumatic otoscopy. Management of AOM requires a thorough clinical exam and updated knowledge of local patterns of microorganisms involved and antimicrobial susceptibility profiles, knowing that the presence of these microorganisms in AOM transtimpanic exudate cultures may vary depending on geographical areas and vaccination. AOM can be treated either with inmediate antibiotic or with observation depending on patients and clinical characteristics. The most common microorganism causing AOM are Pneumococcus, Haemophilus Influenzae, and Moraxella catarrhalis. S. pneumoniae has acquired resistance to penicillin in the last decade that cannot be extrapolated to Amoxicillin. Based on this data Amoxicillin is recommended as the first choice. For amoxicillin failure, cefalosporins or B lactamase can be prescribed. Patients that presents with recurrent AOM should be refered to otolaryngologist for further evaluation and treatment.


title: Household transmission of respiratory viruses – assessment of viral, individual and household characteristics in a population study of healthy Australian adults

text: BACKGROUND: Household transmission of influenza-like illness (ILI) may vary with viral and demographic characteristics. We examined the effect of these factors in a population-based sample of adults with ILI. METHODS: We conducted a prospective cohort study in community-dwelling Australian adults nested within an influenza vaccine effectiveness trial. On presentation with ILI, participants were swabbed for a range of respiratory viruses and asked to return a questionnaire collecting details of household members with or without similar symptoms. We used logistic and Poisson regression to assess the key characteristics of household transmission. RESULTS: 258 participants from multi-occupancy households experienced 279 ILI episodes and returned a questionnaire. Of these, 183 were the primary case in the household allowing assessment of factors associated with transmission. Transmission was significantly associated in univariate analyses with female sex (27% vs. 13%, risk ratio (RR) = 2.13 (1.08, 4.21)) and the presence of a child in the house (33% vs. 17%, RR = 1.90 (1.11, 3.26)). The secondary household attack proportion (SHAP) was 0.14, higher if influenza was isolated (RR = 2.1 (1.0, 4.5)). Vaccinated participants who nonetheless became infected with influenza had a higher SHAP (Incidence RR = 5.24 (2.17, 12.6)). CONCLUSIONS: The increased SHAP in households of vaccinated participants who nonetheless had confirmed influenza infection supports the hypothesis that in years of vaccine mismatch, not only is influenza vaccine less protective for the vaccine recipient, but that the population’s immunity is also lower.


title: Evolving epidemiology and transmission dynamics of coronavirus disease 2019 outside Hubei province, China: a descriptive and modelling study

text: BACKGROUND: The coronavirus disease 2019 (COVID-19) epidemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), began in Wuhan city, Hubei province, in December, 2019, and has spread throughout China. Understanding the evolving epidemiology and transmission dynamics of the outbreak beyond Hubei would provide timely information to guide intervention policy. METHODS: We collected individual information from official public sources on laboratory-confirmed cases reported outside Hubei in mainland China for the period of Jan 19 to Feb 17, 2020. We used the date of the fourth revision of the case definition (Jan 27) to divide the epidemic into two time periods (Dec 24 to Jan 27, and Jan 28 to Feb 17) as the date of symptom onset. We estimated trends in the demographic characteristics of cases and key time-to-event intervals. We used a Bayesian approach to estimate the dynamics of the net reproduction number (R(t)) at the provincial level. FINDINGS: We collected data on 8579 cases from 30 provinces. The median age of cases was 44 years (33–56), with an increasing proportion of cases in younger age groups and in elderly people (ie, aged >64 years) as the epidemic progressed. The mean time from symptom onset to hospital admission decreased from 4·4 days (95% CI 0·0–14·0) for the period of Dec 24 to Jan 27, to 2·6 days (0·0–9·0) for the period of Jan 28 to Feb 17. The mean incubation period for the entire period was estimated at 5·2 days (1·8–12·4) and the mean serial interval at 5·1 days (1·3–11·6). The epidemic dynamics in provinces outside Hubei were highly variable but consistently included a mixture of case importations and local transmission. We estimated that the epidemic was self-sustained for less than 3 weeks, with mean Rt reaching peaks between 1·08 (95% CI 0·74–1·54) in Shenzhen city of Guangdong province and 1·71 (1·32–2·17) in Shandong province. In all the locations for which we had sufficient data coverage of Rt, Rt was estimated to be below the epidemic threshold (ie, <1) after Jan 30. INTERPRETATION: Our estimates of the incubation period and serial interval were similar, suggesting an early peak of infectiousness, with possible transmission before the onset of symptoms. Our results also indicate that, as the epidemic progressed, infectious individuals were isolated more quickly, thus shortening the window of transmission in the community. Overall, our findings indicate that strict containment measures, movement restrictions, and increased awareness of the population might have contributed to interrupt local transmission of SARS-CoV-2 outside Hubei province. FUNDING: National Science Fund for Distinguished Young Scholars, National Institute of General Medical Sciences, and European Commission Horizon 2020.


The Growing Challenge of Avian Influenza


docid: owfnttqr

title: Allergen immunotherapy in the current COVID-19 pandemic: A position paper of AeDA, ARIA, EAACI, DGAKI and GPA: Position paper of the German ARIA Group(A) in cooperation with the Austrian ARIA Group(B), the Swiss ARIA Group(C), German Society for Applied Allergology (AEDA)(D), German Society for Allergology and Clinical Immunology (DGAKI)(E), Society for Pediatric Allergology (GPA)(F) in cooperation with AG Clinical Immunology, Allergology and Environmental Medicine of the DGHNO-KHC(G) and the European Academy of Allergy and Clinical Immunology (EAACI)(H)

text: No abstract available.


title: Reusable elastomeric air-purifying respirators: Physiologic impact on health care workers

text: BACKGROUND: Elastomeric air-purifying respirators offer the benefit of reusability, but their physiological impact on health care workers is unknown. METHODS: Ten health care workers exercised at 2 health care-associated work rates wearing an elastomeric air-purifying respirator. Mixed inhalation/exhalation respirator dead space gases (oxygen, carbon dioxide) were sampled, and physiological parameters were monitored (heart rate, breathing rate, tidal volume, minute volume, oxygen saturation, transcutaneous carbon dioxide). Numerical rating scales were used to evaluate comfort and exertion. RESULTS: Compared with controls (no respirator), significant decreases in the breathing rate at both work rates (P < .05) and increases in tidal volume at the lower work rate (P < .01) were noted with respirator use. Approximately half the subjects had transcutaneous carbon dioxide levels above the upper limit of normal after 1 hour of use. Although well tolerated, comfort was negatively impacted by elastomeric air-purifying respirators wear. CONCLUSION: Reusable elastomeric air-purifying respirators impose little additional physiological burden over the course of 1 hour at usual health care work rates. However, the potential for carbon dioxide retention in a significant proportion of users exists and requires further investigation.


title: StralSV: assessment of sequence variability within similar 3D structures and application to polio RNA-dependent RNA polymerase

text: BACKGROUND: Most of the currently used methods for protein function prediction rely on sequence-based comparisons between a query protein and those for which a functional annotation is provided. A serious limitation of sequence similarity-based approaches for identifying residue conservation among proteins is the low confidence in assigning residue-residue correspondences among proteins when the level of sequence identity between the compared proteins is poor. Multiple sequence alignment methods are more satisfactory--still, they cannot provide reliable results at low levels of sequence identity. Our goal in the current work was to develop an algorithm that could help overcome these difficulties by facilitating the identification of structurally (and possibly functionally) relevant residue-residue correspondences between compared protein structures. RESULTS: Here we present StralSV (structure-alignment sequence variability), a new algorithm for detecting closely related structure fragments and quantifying residue frequency from tight local structure alignments. We apply StralSV in a study of the RNA-dependent RNA polymerase of poliovirus, and we demonstrate that the algorithm can be used to determine regions of the protein that are relatively unique, or that share structural similarity with proteins that would be considered distantly related. By quantifying residue frequencies among many residue-residue pairs extracted from local structural alignments, one can infer potential structural or functional importance of specific residues that are determined to be highly conserved or that deviate from a consensus. We further demonstrate that considerable detailed structural and phylogenetic information can be derived from StralSV analyses. CONCLUSIONS: StralSV is a new structure-based algorithm for identifying and aligning structure fragments that have similarity to a reference protein. StralSV analysis can be used to quantify residue-residue correspondences and identify residues that may be of particular structural or functional importance, as well as unusual or unexpected residues at a given sequence position. StralSV is provided as a web service at http://proteinmodel.org/AS2TS/STRALSV/.