title: Review of Issues and Challenges of Practicing Emergency Medicine Above 30,000-Feet Altitude: 2 Anonymized Cases

text: Abstract We present 2 anonymized cases to identify issues and challenges associated with long-haul in-flight medical emergencies. The first case involved a middle-aged man with a history of carditis on a systemic steroid who developed vomiting and rigor. Four physicians, including a pediatric intensivist, responded to the emergency call. In the second case, a pediatric trainee who was the only onboard medical personnel was summoned for help when a middle-aged man developed acute shortness of breath while traveling on a commercial flight. The cases illustrate the challenges and issues on the critical decisions of diagnosis, resuscitation, and whether the flight had to be returned or diverted. An extensive literature search is made to summarize the evidence available for these decisions and challenges. Epidemiology and outcomes associated with these medical emergencies are reviewed. In-flight medical emergencies are not rare. Physicians of all disciplines should be prepared to deal with these emergencies and make sensible decisions when equipment and resources are likely to be limited.


title: Evaluation of pedestrian wind comfort near ‘lift-up’ buildings with different aspect ratios and central core modifications

text: Abstract Owing to the void space at lower heights, lift-up buildings have high building permeability at ground level and subsequently improve the air circulation in congested urban areas. Despite this advantage, the lift-up design has been sparsely adopted for buildings in urban areas partly because of the lack of understanding of the combined effects of building dimensions and lift-up design on the surrounding pedestrian level wind (PLW) field. Therefore, this study aims to investigate the influence of lift-up buildings with different aspect ratios (height/width) on the surrounding PLW field and pedestrian wind comfort level. Five lift-up buildings with aspect ratios 4:1 to 0.5:1 were tested in a boundary layer wind tunnel and results were compared with those of five buildings with similar dimensions but without lift-up design. The results reveal a strong dependence of the maximum wind speed in lift-up areas with building height, which results subsequently a small area of acceptable wind conditions near tall and slender lift-up buildings. Lift-up designs adopted for short and wide buildings produce larger areas of pedestrian wind comfort. The central cores modified with corner modifications are effective in increasing the pedestrian wind comfort in the lift-up area of tall and slender buildings.


title: Las estadísticas sanitarias y la invisibilidad por sexo y de género durante la epidemia de COVID-19

text: ABSTRACT Reports on COVID-19 from the Spanish Health Ministry are valuable, but incomplete, with the perverse effect that the susceptibility to COVID-19 by sex is unclear. Prevalence of COVID-19 by sexes differs between countries. The trend in Spain shows an unequal pattern, initially more frequent in men, but women outnumbered them from March 31, after two weeks lockdown. Infections are more frequent in women than in men in close contact with probable/confirmed COVID-19 cases. Consistent with deaths in men, they are hospitalized more frequently than women: Significant gender differences in signs/symptoms can drive this pattern, already observed in other pathologies. In late April, excess mortality is the same in women (67%) than in men (66%). But, lack of exhaustive information on deaths from COVID-19 in non-hospitalized patients may contribute to lower notification of deaths in women. Invisibility of data by sex and gender is probably affecting negatively women with COVID -19 more than men.


title: Curation of viral genomes: challenges, applications and the way forward

text: BACKGROUND: Whole genome sequence data is a step towards generating the 'parts list' of life to understand the underlying principles of Biocomplexity. Genome sequencing initiatives of human and model organisms are targeted efforts towards understanding principles of evolution with an application envisaged to improve human health. These efforts culminated in the development of dedicated resources. Whereas a large number of viral genomes have been sequenced by groups or individuals with an interest to study antigenic variation amongst strains and species. These independent efforts enabled viruses to attain the status of 'best-represented taxa' with the highest number of genomes. However, due to lack of concerted efforts, viral genomic sequences merely remained as entries in the public repositories until recently. RESULTS: VirGen is a curated resource of viral genomes and their analyses. Since its first release, it has grown both in terms of coverage of viral families and development of new modules for annotation and analysis. The current release (2.0) includes data for twenty-five families with broad host range as against eight in the first release. The taxonomic description of viruses in VirGen is in accordance with the ICTV nomenclature. A well-characterised strain is identified as a 'representative entry' for every viral species. This non-redundant dataset is used for subsequent annotation and analyses using sequenced-based Bioinformatics approaches. VirGen archives precomputed data on genome and proteome comparisons. A new data module that provides structures of viral proteins available in PDB has been incorporated recently. One of the unique features of VirGen is predicted conformational and sequential epitopes of known antigenic proteins using in-house developed algorithms, a step towards reverse vaccinology. CONCLUSION: Structured organization of genomic data facilitates use of data mining tools, which provides opportunities for knowledge discovery. One of the approaches to achieve this goal is to carry out functional annotations using comparative genomics. VirGen, a comprehensive viral genome resource that serves as an annotation and analysis pipeline has been developed for the curation of public domain viral genome data . Various steps in the curation and annotation of the genomic data and applications of the value-added derived data are substantiated with case studies.


title: Comparisons of envelope through 5B sequences of infectious bronchitis coronaviruses indicates recombination occurs in the envelope and membrane genes

text: Abstract A 1.78kb sequence, including the E, M, 5a and 5b genes, and the intergenic region between the M and 5a genes, of six US strains of infectious bronchitis (corona)virus (IBV) were sequenced and compared to the published sequences for two additional strains. The overall identities as determined through pairwise analyses of nucleotide sequences of the entire 1.78kb region ranged from 90 to 99%, with the 5b open reading frame (ORF) having the greatest identity (94–99%) while the identities of the E, 5a and M ORFs ranged from 87 to 100%. Nucleotide sequencing of recent field isolates from Alabama (Ala1) and California (Cal3) revealed distinct shifts in homology in the M gene, indicating two apparent recombination events between the Holland 52/Mass41-like strain and an Ark-like strain, both origins of commonly used vaccine strains. Putative sites of recombination could also be identified in both the E and M ORFs of laboratory strains of IBV.


Missing information in animal surveillance of MERS-CoV


title: Pathogen survival in the external environment and the evolution of virulence

text: Recent studies have provided evolutionary explanations for much of the variation in mortality among human infectious diseases. One gap in this knowledge concerns respiratory tract pathogens transmitted from person to person by direct contact or through environmental contamination. The sit‐and‐wait hypothesis predicts that virulence should be positively correlated with durability in the external environment because high durability reduces the dependence of transmission on host mobility. Reviewing the epidemiological and medical literature, we confirm this prediction for respiratory tract pathogens of humans. Our results clearly distinguish a high‐virulence high‐survival group of variola (smallpox) virus, Mycobacterium tuberculosis, Corynebacterium diphtheriae, Bordetella pertussis, Streptococcus pneumoniae, and influenza virus (where all pathogens have a mean percent mortality 0.01% and mean survival time >10 days) from a low‐virulence low‐survival group containing ten other pathogens. The correlation between virulence and durability explains three to four times of magnitude of difference in mean percent mortality and mean survival time, using both across‐species and phylogenetically controlled analyses. Our findings bear on several areas of active research and public health policy: (1) many pathogens used in the biological control of insects are potential sit‐and‐wait pathogens as they combine three attributes that are advantageous for pest control: high virulence, long durability after application, and host specificity; (2) emerging pathogens such as the‘hospital superbug’methicillin‐resistant Staphylococcus aureus (MRSA) and potential bioweapons pathogens such as smallpox virus and anthrax that are particularly dangerous can be discerned by quantifying their durability; (3) hospital settings and the AIDS pandemic may provide footholds for emerging sit‐and‐wait pathogens; and (4) studies on food‐borne and insect pathogens point to future research considering the potential evolutionary trade‐offs and genetic linkages between virulence and durability.


title: Immune responses to RNA-virus infections of the CNS

text: A successful outcome for the host of virus infection of the central nervous system (CNS) requires the elimination of the virus without damage to essential non-renewable cells, such as neurons. As a result, inflammatory responses must be tightly controlled, and many unique mechanisms seem to contribute to this control. In addition to being important causes of human disease, RNA viruses that infect the CNS provide useful models in which to study immune responses in the CNS. Recent work has shown the importance of innate immune responses in the CNS in controlling virus infection. And advances have been made in assessing the relative roles of cytotoxic T cells, antibodies and cytokines in the clearance of viruses from neurons, glial cells and meningeal cells.


title: Serological detection of infection dynamics for respiratory viruses among dairy calves

text: Abstract The aim of this study is to reveal infection dynamics of bovine respiratory syncytial virus (BRSV), bovine parainfluenza virus type 3 (PI-3), bovine herpesvirus 1 (BHV-1), bovine viral diarrhea virus (BVDV), bovine adenovirus type 3 (BAV-3) and bovine coronavirus (BCoV), which are important viral pathogens of respiratory disease complex in ruminants. Through such an analysis, the regression period of maternally derived antibodies and optimum vaccination time in calves can be recommended. A total of 10 farms were grouped as large (4)-, medium (2)- and small (4)- sized enterprises according to their animal population. Newborn calves (n: 94) delivered during a calendar month on the farms were studied. Blood samples were collected from these calves during their 1st, 2nd, 3rd, 4th, 6th, 8th, 10th and 12th months of age. Blood samples were also taken from their dams during the first sampling. Neutralizing antibody titers were detected using the serum neutralization test (SN50). New PI-3 and BVDV infections at the early stages of life were determined in the calves. Maternal antibodies began to decrease in the 2nd month for BRSV, BHV-1 and BAV-3 (97.8%, 25.5% and 91.4%) and in the 3rd month for PI-3, BVDV and BCoV (85.1%, 67% and 93.6%). It was concluded that maternal antibodies begin to decrease after the 1st month and that the possible first exposure of calves to respiratory viruses is after the 2nd month. Therefore, it is recommended that the first vaccination program including prime and booster doses can be applied between 2 and 4 months of age. Furthermore, re-vaccination of animals at 6 months after the booster dose is also suggested.


title: Predictive model of diagnosing probable cases of severe acute respiratory syndrome in febrile patients with exposure risk

text: Abstract Study objective Since the World Health Organization issued a global alert about severe acute respiratory syndrome (SARS) on March 12, 2003, the illness has become a major public health challenge worldwide. The objective of this study is to identify the clinical risk factors of SARS and to develop a scoring system for early diagnosis. Methods The detailed clinical data of all patients presenting to the emergency department (ED) with a temperature higher than 38.0°C (100.3°F), documented at home or at the ED, and risks of exposure to SARS within 14 days were assessed. The diagnosis of probable SARS was made according to the definition of the Centers for Disease Control and Prevention. Items with significant differences among symptoms, signs, and laboratory tests on presentation between SARS and non-SARS groups were determined and used to develop the scoring system. Results Seventy patients were enrolled and 8 were diagnosed as probably having SARS. None of the initially discharged patients or their relatives developed SARS. Compared with the non-SARS group, the SARS group was younger (33.9±15.9 years versus 44±9.8 years; P=.02), had a higher percentage of fever prolonged more than 5 days (87.5% versus 6.5%; P<.01), myalgia (75% versus 27.4%; P=.01), and diarrhea (50% versus 9.7%; P=.02); had less occurrence of cough before or during fever (0% versus 64.5%; P=.01); and had lower absolute lymphocyte (0.9±0.3×109/L versus 1.5±1.1×109/L; P<.01) and platelet counts (144.1±36.3×109/L versus 211.6±78.8×109/L; P=.02). A 4-item symptom score based on the presence of cough before or concomitant with fever, myalgia, diarrhea, and rhinorrhea or sore throat detects SARS with 100% sensitivity and 75.9% specificity; a 6-item clinical score based on lymphopenia (<1.0×109/L), thrombocytopenia (<150×109/L) and the 4 symptom items detects SARS with 100% sensitivity and 86.3% specificity. Conclusion Certain symptoms and laboratory tests indicate higher risk of febrile probable SARS. In nonendemic areas, the febrile patients with recent contact with SARS or travel history to endemic areas could be screened for the probability of SARS by the use of clinical and symptom scores.


title: Acute promyelocytic leukaemia lying under the mask of COVID‐19‐a diagnostic and therapeutic conundrum

text: The diagnosis and management of acute promyelocytic leukaemia (APML) in the context COVID‐19 poses a challenge for clinicians. We present a case illustrating this due to the masking of the typical laboratory pattern of APML coagulopathy and the potential heightened risks of thrombosis and differentiation syndrome (DS) when the two conditions are combined.


title: Psychological crisis intervention during the outbreak period of new coronavirus pneumonia from experience in Shanghai

text: Abstract Since the middle of December 2019, human-to-human transmission of novel coronavirus pneumonia (NCP) has occurred among close contacts. At the same time, greater attention should be paid to psychological crisis intervention (PCI) among affected populations, for the timely prevention of inestimable damage from a secondary psychological crisis. PCI has been initiated via remote (telephone and internet) and onsite medical services to help medical workers, patients, and others affected to overcome any psychological difficulties. This paper outlines experiences based on the work of the Shanghai Medical Team.


title: Antibody testing for coronavirus disease 2019: not ready for prime time

text: The tests need work, and fundamental questions remain about immunity


Neurological Manifestations of COVID-19 - Continually Evolving and Perplexing


title: Sympatric speciation in parasites – what is sympatry?

text: Abstract Parasites account for a large part of known species diversity and are considered to have a high potential for sympatric speciation. However, the frequency of sympatric divergence in these organisms will depend on the definition of sympatry that one uses. Like many of our current species concepts, the typical definition of sympatry is not widely applicable to parasites. Revisiting the historically defined conditions for sympatric speciation and considering the situations in which we might regard parasites as being sympatric leads us to question the classic prediction that parasites have a greater tendency to speciate in sympatry than do free-living organisms.


title: Apelin-potential therapy for COVID-19?

text: We believe that, in parallel to the attempts for direct blockade of the SARS-CoV-2 penetration into host cell and repurposing drugs, finding new therapeutic strategies for patients with lung injury or cardiovascular complications/coagulopathies associated with COVID-19 should be paid particular attention. Apelin or its receptor agonists are of great potential treatment for COVID-19 through suppressing angiotensin-converting enzyme (ACE) and angiotensin II (Ang-II) production, as well as, down-regulating angiotensin receptor 1 (AT1R) and ACE2 up-regulation. These drugs have potential to improve acute lung injury and cardiovascular/coagulopathy complications in COVID-19 which are associated with elevated Ang-II/Ang(1–7) ratio.


Domestic Abuse during COVID-19 - What about the boys?


title: Traumatic non-missile penetrating transnasal anterior skull-base fracture and brain injury with cerebrospinal fluid leak: intraoperative leak detection and an effective reconstruction procedure for a localized skull base defect especially after COVID-19 outbreak

text: Abstract BACKGROUND Cerebrospinal fluid leakage in penetrating skull base injury is relatively rare compared to close head injury involving skull base fracture. CASE DESCRIPTION We report a case of a 65-year-old beekeeping man who presented with epistaxis and serous rhinorrhea. When he fell down on the ground near his bee boxes, a garden pole poked into his right nostril. He instantly removed the pole from his nostril by himself. Immediately after the removal of the pole, he developed some nasal bleeding and serous rhinorrhea. He then drove to our emergency room. Computed tomography showed pneumocephalus with minor cerebral contusion in the left frontal lobe, and penetrating injury in the left anterior skull base. His cerebrospinal fluid (CSF) leakage did not resolve spontaneously within one week after the injury under a strict bed rest. We repaired the CSF leakage using a fat (adipose tissue)-on-fascia autograft plug and caulked the defect in the anterior skull base with the fat-on-fascia graft (FFG) plug through the left nostril under endoscopic vision. The CSF rhinorrhea was successfully controlled. Intranasal local application of fluorescein aided in the detection of the flow direction of CSF leakage. CONCLUSIONS Endonasal endoscopic caulking of a skull base defect using FFG plug is useful for CSF leakage due to localized skull base defect, in particular for the post-COVID-19 era, because it is simple, low-cost, and timesaving: requiring no special skills or no sophisticated instruments, thus reducing infection risks during the surgery. (239 words)


title: Conventional and Specific-Pathogen Free Rats Respond Differently to Anesthesia and Surgical Trauma

text: Specific-pathogen free (SPF) animals were introduced in the 1960s to minimize disease and infection as variables in biomedical research. Our aim was to examine differences in physiological response in rat colonies bred and housed in a conventional versus SPF facility, and implications for research. Sprague-Dawley rats were anesthetized and catheterized for blood and pressure monitoring, and electrocardiogram (ECG) leads implanted. Hematology was assessed, and coagulation profile using rotational thromboelastometry. Health screening was outsourced to Cerberus Sciences. SPF rats had significantly lower pulse pressure (38% decrease), arrhythmias and prolonged QTc (27% increase) compared to conventional rats. No arrhythmias were found in conventional rats. SPF rats had significantly higher white cell, monocyte, neutrophil and lymphocyte counts, and were hyperfibrinolytic, indicated by EXTEM maximum lysis >15%. Independent assessment revealed similar pathogen exclusion between colonies, with the exception of Proteus in SPF animals. Returning to a conventional facility restored normal host physiology. We conclude that SPF animals displayed an abnormal hemodynamic, hematological and hemostatic phenotype in response to anesthesia and surgery, and provide a number of recommendations to help standardize research outcomes and translation.


title: Challenges in Drug Development Posed by the COVID‐19 Pandemic: An Opportunity for Clinical Pharmacology

text: The unprecedented challenges posed by the coronavirus disease 2019 (COVID‐19) pandemic highlight the urgency for applying clinical pharmacology and model‐informed drug development in (i) dosage optimization for COVID‐19 therapies, (ii) approaching therapeutic dilemmas in clinical trial settings, and (iii) maximizing value of information from impacted non–COVID‐19 trials. More than ever, we have a responsibility for adaptive evidence synthesis with a Totality of Evidence mindset in this race against time across biomedical research, clinical practice, drug development, and regulation.


title: A Guide to Viral Inclusions, Membrane Rearrangements, Factories, and Viroplasm Produced During Virus Replication

text: Abstract Virus replication can cause extensive rearrangement of host cell cytoskeletal and membrane compartments leading to the “cytopathic effect” that has been the hallmark of virus infection in tissue culture for many years. Recent studies are beginning to redefine these signs of viral infection in terms of specific effects of viruses on cellular processes. In this chapter, these concepts have been illustrated by describing the replication sites produced by many different viruses. In many cases, the cellular rearrangements caused during virus infection lead to the construction of sophisticated platforms in the cell that concentrate replicase proteins, virus genomes, and host proteins required for replication, and thereby increase the efficiency of replication. Interestingly, these same structures, called virus factories, virus inclusions, or virosomes, can recruit host components that are associated with cellular defences against infection and cell stress. It is possible that cellular defence pathways can be subverted by viruses to generate sites of replication. The recruitment of cellular membranes and cytoskeleton to generate virus replication sites can also benefit viruses in other ways. Disruption of cellular membranes can, for example, slow the transport of immunomodulatory proteins to the surface of infected cells and protect against innate and acquired immune responses, and rearrangements to cytoskeleton can facilitate virus release.


title: Occasional review: Influenza in COPD: pathogenesis, prevention, and treatment

text: Influenza viruses cause respiratory tract infections that in patients with underlying lung diseases such as chronic obstructive pulmonary disease (COPD) are associated with exacerbations and excess morbidity and mortality. Typically, influenza B is associated with relatively mild, local outbreaks, whereas influenza A is the cause of world-wide pandemics. Upon infection, two antigens present on the viral surface, hemagglutinin and neuraminidase result in human immunity, but since many subtypes of these antigens exist that vary over time, immunity in the population is blunted. Vaccination is advocated in high-risk groups including patients with underlying (lung) diseases and in the elderly, and needs to be repeated annually with vaccines expected to cover the expected change in viral antigenicity. When started early, antiviral drugs, especially neuraminidase-inhibitors can be prescribed in adjunct to nonspecific interventions in an attempt to shorten disease duration and to prevent complications in case of an influenza infection. Currently, the effectiveness of antiviral drugs specifically in patients with COPD has not been proven.


title: Improving preparedness for the next flu pandemic

text: Pandemic influenza remains the single greatest threat to global heath security. Efforts to increase our preparedness, by improving predictions of viral emergence, spread and disease severity, by targeting reduced transmission and improved vaccination and by mitigating health impacts in low- and middle-income countries, should receive renewed urgency.


title: Management of IBD during the COVID-19 outbreak: resetting clinical priorities

text: The coronavirus disease (COVID-19) worldwide outbreak has led to a dramatic challenge for all healthcare systems, including inflammatory bowel disease (IBD) centres. Here, we describe the fast changes and clinical issues that IBD specialists could face during this SARS-CoV-2 infection pandemic, highlighting the potential rearrangements of care and resetting of clinical priorities.


title: Exercise testing in survivors of intensive care—is there a role for cardiopulmonary exercise testing?

text: Abstract Purpose The aims of this study were to assess the feasibility of cardiopulmonary exercise testing (CPET) for the early assessment of cardiorespiratory fitness in general adult intensive care unit (ICU) survivors and to characterize the pathophysiology of exercise limitation in this population. Methods Fifty general ICU survivors (ventilated for ≥5 days) performed a maximal cycle ergometer CPET within 6 weeks of hospital discharge. Health-related quality of life was measured by the Medical Outcome Study Short Form 36 version 2.0 questionnaire. Results Fifty patients (median age, 57 years; median Acute Physiology And Chronic Health Evaluation II score, 16) completed a CPET 24 ± 14 days after hospital discharge with no adverse events. Significant exercise limitation was present with peak Vo 2 56% ± 16% predicted and anaerobic threshold (AT) 41% ± 13% of peak predicted Vo 2. Prospectively stratified subgroup comparison showed that patients ventilated for 14 days or more had a significantly lower AT and peak Vo 2 than those ventilated for 5 to 14 days (AT: 9.6 vs 11.7 mL/kg per minute O2, P = .009; peak Vo 2: 12.9 vs 15.3 mL/kg per minute O2, P = .022). At peak exercise, heart rate reserve was 25% ± 14%, breathing reserve was 47% ± 19%, and the respiratory exchange ratio was 0.96 ± 0.11. Ventilatory equivalents for CO2 (Eqco 2) were 39 ± 9. Conclusions Significant exercise limitation is evident in patients who have had critical illness. Etiology of exercise limitation appears multifactorial, with general deconditioning and muscle weakness as major contributory factors. Early CPET appears a practical method of assessing exercise capacity in ICU survivors. Cardiopulmonary exercise testing could be used to select patients who may benefit most from a targeted physical rehabilitation program, aid in exercise prescription, and help assess the response to intervention.


title: Antiviral Innate Immune Response Interferes with the Formation of Replication-Associated Membrane Structures Induced by a Positive-Strand RNA Virus

text: Infection with nidoviruses like corona- and arteriviruses induces a reticulovesicular network of interconnected endoplasmic reticulum (ER)-derived double-membrane vesicles (DMVs) and other membrane structures. This network is thought to accommodate the viral replication machinery and protect it from innate immune detection. We hypothesized that the innate immune response has tools to counteract the formation of these virus-induced replication organelles in order to inhibit virus replication. Here we have investigated the effect of type I interferon (IFN) treatment on the formation of arterivirus-induced membrane structures. Our approach involved ectopic expression of arterivirus nonstructural proteins nsp2 and nsp3, which induce DMV formation in the absence of other viral triggers of the interferon response, such as replicating viral RNA. Thus, this setup can be used to identify immune effectors that specifically target the (formation of) virus-induced membrane structures. Using large-scale electron microscopy mosaic maps, we found that IFN-β treatment significantly reduced the formation of the membrane structures. Strikingly, we also observed abundant stretches of double-membrane sheets (a proposed intermediate of DMV formation) in IFN-β-treated samples, suggesting the disruption of DMV biogenesis. Three interferon-stimulated gene products, two of which have been reported to target the hepatitis C virus replication structures, were tested for their possible involvement, but none of them affected membrane structure formation. Our study reveals the existence of a previously unknown innate immune mechanism that antagonizes the viral hijacking of host membranes. It also provides a solid basis for further research into the poorly understood interactions between the innate immune system and virus-induced replication structures.


title: Fixed-cell immunoperoxidase technique for the study of surface antigens induced by the coronavirus of transmissible gastroenteritis (TGEV)

text: Abstract An immunoperoxidase technique performed on the TGEV-infected cells was developed for detection of virus-induced antigens. The presence of M antigen of TGEV on the surface of infected cells was demonstrated by this technique. This finding is in contrast to the M protein of murine hepatitis coronavirus which migrates to the Golgi apparatus but is not transported to the plasma membrane. The time course of appearance M and S antigens on the surface of TGEV-infected cell can be studied by this technique.


title: The “biosecuritization” of healthcare delivery: Examples of post-9/11 technological imperatives

text: This paper develops the concept of “biosecuritization” to describe new instantiations of the technological imperative in healthcare. Many discourses and practices surrounding hospitals’ new investments in information and communication technologies tend to revolve around security provision. Oftentimes, however, scenarios of extreme and exceptional circumstances are used to justify the implementation of identification and tracking technologies that may be more about managerial control than patient care. Drawing upon qualitative research in 23 U.S. hospitals from 2007 to 2009, our analysis focuses on hospitals’ deployment of identification and location technologies that manage patients, track personnel, and generate data in real-time. These systems are framed as aiding in the process of managing supplies and medications for pandemic flu outbreaks, monitoring exposure patterns for infectious diseases, and helping triage or manage the location and condition of patients during mass casualty disasters. We show that in spite of the framing of security and emergency preparedness, these technologies are primarily managerial tools for hospital administrators. Just as systems can be used to track infection vectors, those same systems can be used on a daily basis to monitor the workflow of hospital personnel, including nurses, physicians, and custodial staff, and to discipline or reward according to performance. In other words, the biosecuritization modality of the technological imperative leads to the framing of medical progress as the “rationalization” of organizations through technological monitoring, which is intended to promote accountability and new forms of responsibilization of healthcare workers.


title: Withdrawing mycophenolate mofetil in treating a young kidney transplant recipient with COVID-19: A case report

text: RATIONALE: Coronavirus disease 2019 (COVID-19) is a novel infectious disease and became a global issue. Treatment of COVID-19 especially in solid organ transplant recipients is empirical and controversial, especially the adjustment of the immunosuppressants. PATIENT CONCERNS: A 29-year-old kidney transplant recipient with the symptoms of COVID-19 pneumonia. DIAGNOSES: COVID-19 pneumonia after kidney transplantation. INTERVENTIONS: He was treated with modified immunosuppressants (unchanged dose of tacrolimus and oral corticosteroids while discontinuing mycophenolate mofetil (MMF)), antibiotics, interferon α-2b inhalation and traditional Chinese medicine. OUTCOMES: He recovered from COVID-19 pneumonia after 29 days of hospitalization. And the renal function (measured as blood urea nitrogen, serum creatinine, and urine protein) returned to normal. LESSONS: In certain group of COVID-19 (e.g., mild to moderate cases, young patients without comorbidities), a reduction instead of an overall withdrawal of immunosuppressant in kidney transplant recipients is feasible.


title: Combination of multiplex reverse-transcription loop-mediated isothermal amplification with an immunochromatographic strip for subtyping influenza A virus

text: Abstract Considering the fatal human victims and economic loss by the annual epidemic influenza virus, the development of a rapid and convenient genetic analysis methodology is demanding for timely on-site pathogen detection. In this study, we utilized reverse-transcription loop-mediated isothermal amplification (RT-LAMP) for multiplex target gene amplification, and the resultant amplicons were analyzed on the immunochromatographic strip (ICS) for subtyping influenza A virus. Through the optimized primer design, reaction temperature and time, and concentration of enzymes (Bst DNA polymerase and AMV reverse transcriptase) and dNTP, the HA (H1, H3, and H5 gene) and conserved M gene were amplified. The ICS contains two test lines in addition to a control line in order to detect the presence of the HA and M gene, thereby informing us of influenza virus A type as well as its subtype (H1N1, H3N2, and H5N1). The combination of the multiplex RT-LAMP with the ICS could be complete in 40min and the pathotyping and subtyping of influenza A virus were performed even with 10 copies of viral RNA templates. Moreover, the subtyping of clinical samples, which were obtained from patients infected by influenza A virus was successfully confirmed using the multiplex RT-LAMP and ICS techniques, showing great feasibility of our methodology for real sample analysis with high speed, simplicity and sensitivity.


title: Third Tofo Advanced Study Week on Emerging and Re-emerging Viruses, 2018

text: Abstract The Third Tofo Advanced Study Week on Emerging and Re-Emerging Viruses (3rd TASW) was held in Praia do Tofo, Mozambique, from September 02 to 06, 2018. It brought together 55 participants from 10 African countries as well as from Belgium, China, Germany, Singapore, and the USA. Meeting sessions covered aspects of the epidemiology, diagnosis, molecular and structural biology, vaccine development, and antiviral drug discovery for emerging RNA viruses that are current threats in Africa and included flaviviruses (dengue and Zika), alphaviruses (chikungunya), coronaviruses, filoviruses (Ebola), influenza viruses, Crimean Congo hemorrhagic fever virus, Rift Valley fever Virus, Lassa virus, and others. Data were presented on recent flavivirus and/or chikungunyavirus outbreaks in Angola, Burkina Faso, and Mozambique. In addition, these viruses are endemic in many sub-Saharan countries. The TASW series on emerging viruses is unique in Africa and successful in promoting collaborations between researchers in Africa and other parts of the world, as well as among African scientists. This report summarizes the lectures held at the meeting and highlights advances in the field.


Effect of COVID-19 pandemic on cancer clinician decision making: Known knowns and known unknowns


title: Symptom Severity Patterns in Experimental Common Colds and Their Usefulness in Timing Onset of Illness in Natural Colds

text: Mean total symptom severity scores for subjects with experimental rhinovirus colds peak 48 h after viral inoculation. Also, total symptom scores for natural rhinovirus and nonrhinovirus colds peaked on day 2 of illness in a long-term, noncompensated epidemiology study. In contrast, the mean total symptom scores for compensated patients receiving placebo in natural cold treatment trials peaked on day 1. Comparisons by day indicated that scores for symptoms reported as occurring on day 1 in the natural cold treatment trials corresponded with experimental cold scores for symptoms reported 48 h after viral inoculation. Comparisons of frequency and cumulative distribution scores for the 2 groups indicated that natural colds in the treatment trials were of longer duration than reported. A mean total symptom severity score of ⩽7 would capture 95% of experimental colds 24 h after inoculation while excluding 30.5% of natural colds on day 1 of illness. Histories given by compensated patients in natural cold treatment trials are inaccurate.


title: Predicting Professional Quality of Life and Life Satisfaction in Spanish Nurses: A Cross-Sectional Study

text: Background: Dealing with suffering, grief, and death on a daily basis, together with the particular working conditions, may produce high levels of burnout in nurses, and hinder their well-being. The purpose of this research is to study the effect of self-care and self-compassion on nurses’ professional quality of life and well-being. Methods: The research had a cross-sectional design, used correlational methodology and a structural equation model was hypothesized. Along the study, 210 nurses from the Healthcare Public System of the Balearic Islands, participated. The study took place from June to September 2018. Results: The hypothesized model showed an overall adequate fit. Practice environment predicted both self-care and self-compassion, whereas nursing stress did not. Self-care and self-compassion predicted nurses’ professional quality of life, whereas the practice environment and nursing stress were not predictors. Finally, professional quality of life showed a positive relationship with life satisfaction. Conclusions: The study presents a comprehensive structural equation model in which self-care and self-compassion are the best predictors of nurses’ professional quality of life. A direct relation of professional quality of life and nurses’ well-being has also been found, while controlling for the effects of nurses’ practice environment and stress.


title: Evaluation of protection conferred by a vaccination program based on the H120 and CR88 commercial vaccines against a field variant of avian infectious bronchitis virus

text: Abstract Due to serotype variations among different avian infectious bronchitis viruses isolated in Tunisia since 2000, protection of chicks, especially broiler flocks, with Mass H120 vaccine often fails. Therefore, association of CR88 (793B type) with H120 vaccines was used for better response. Challenge experiments were then conducted to evaluate tracheal and renal cross-protection in chickens immunized via nasal and eye drops. Conferred protection was measured by clinical signs and macroscopic lesions observed, based on scores attributed according to their severities. The results showed a low protection conferred by H120 alone, as vaccination did not reduce tracheal and kidney lesions (70% scored as 3) after TN20/00 virus challenge, which also led to 10% mortality. Conversely, the challenge results indicated that the combination of the 2 strains (H120/CR88) allow high protection. Based on the results of the challenge experiments, a vaccination protocol coupling CR88 to H120 was applied for industrial broiler flocks. Clinical observations and serological results confirmed that association of heterologous serotypes (H120 and CR88 vaccines) increased the levels of protection against infectious bronchitis viruses compared with the H120 vaccine given alone.


Toward a clinically based classification of disease severity for paediatric COVID-19 – Authors' reply


title: Telomeres and COVID‐19

text: The medical, public health, and scientific communities are grappling with monumental imperatives to contain COVID‐19, develop effective vaccines, identify efficacious treatments for the infection and its complications, and find biomarkers that detect patients at risk of severe disease. The focus of this communication is on a potential biomarker, short telomere length (TL), that might serve to identify patients more likely to die from the SARS‐CoV‐2 infection, regardless of age. The common thread linking these patients is lymphopenia, which largely reflects a decline in the numbers of CD4/CD8 T cells but not B cells. These findings are consistent with data that lymphocyte TL dynamics impose a limit on T‐cell proliferation. They suggest that T‐cell lymphopoiesis might stall in individuals with short TL who are infected with SARS‐CoV‐2.


title: Exaptive Evolution of Target of Rapamycin Signaling in Multicellular Eukaryotes

text: Target of rapamycin (TOR) is a protein kinase that coordinates metabolism with nutrient and energy availability in eukaryotes. TOR and its primary interactors, RAPTOR and LST8, have been remarkably evolutionarily static since they arose in the unicellular last common ancestor of plants, fungi, and animals, but the upstream regulatory mechanisms and downstream effectors of TOR signaling have evolved considerable diversity in these separate lineages. Here, I focus on the roles of exaptation and adaptation in the evolution of novel signaling axes in the TOR network in multicellular eukaryotes, concentrating especially on amino acid sensing, cell-cell signaling, and cell differentiation.


docid: lxyvkgdd

title: Development and statistical validation of a guinea pig model for vaccine potency testing against Infectious Bovine Rhinothracheitis (IBR) virus

text: Infectious Bovine Rhinothracheitis (IBR) caused by bovine herpesvirus 1 (BoHV-1) infection is distributed worldwide. BoHV-1 either alone or in association with other respiratory cattle pathogens causes significant economic losses to the livestock industry. The aim of this work was to validate a guinea pig model as an alternative method to the current BoHV-1 vaccine potency testing in calves. Guinea pigs were immunized with two doses of vaccine, 21 days apart and sampled at 30 days post vaccination (dpv). BoHV-1 antibody (Ab) response to vaccination in guinea pigs, measured by ELISA and virus neutralization (VN), was statistically compared to the Ab response in cattle. The guinea pig model showed a dose–response relationship to the BoVH-1 antigen concentration in the vaccine and it was able to discriminate among vaccines containing 1 log(10) difference in its BoHV-1 concentration with very good repeatability and reproducibility (CV ≤ 20%). A regression analysis of the Ab titers obtained in guinea pigs and bovines at 30 and 60 dpv, respectively, allowed us to classify vaccines in three potency categories: “very satisfactory”, “satisfactory” and “unsatisfactory”. Bovines immunized with vaccines corresponding to each of these three categories were experimentally challenged with BoVH-1 virus, the level of protection, as measured by reduction of virus shedding and disease severity, correlated well with the vaccine category used. Data generated by 85 experiments, which included vaccination of calves and guinea pigs with 18 reference vaccines of known potency, 8 placebos and 18 commercial vaccines, was subjected to statistical analysis. Concordance analysis indicated almost perfect agreement between the model and the target species for Ab titers measured by ELISA and almost perfect to substantial agreement when Ab titers were measured by VN. Taken together these results indicate that the developed guinea pig model represents a novel and reliable tool to estimate batch-to-batch vaccine potency and to predict efficacy of killed BoHV-1 veterinary vaccines.


docid: texnuvvp

title: Investigation of the pharmacophore space of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) NTPase/helicase by dihydroxychromone derivatives

text: Abstract Aryl diketoacids have been identified as the first SARS-CoV NTPase/helicase inhibitors with a distinct pharmacophore featuring an arylmethyl group attached to a diketoacid. In order to search for the pharmacophore space around the diketoacid core, three classes of dihydroxychromone derivatives were prepared. Based on SAR study, an extended feature of the pharmacophore model of SARS-CoV NTPase/helicase was proposed which is constituted of a diketoacid core, a hydrophobic arylmethyl substituent, and a free catechol unit.


“COVID-19 Drive Through Testing: An Effective Strategy for Conserving Personal Protective Equipment”


title: Risk of Mycoplasma bovis transmission from contaminated sand bedding to naive dairy calves

text: Abstract The objective of this study was to evaluate the possible transmission of Mycoplasma bovis from positive sand bedding to naïve dairy calves. Twelve preweaned Holstein bull calves were blocked in pairs and randomly assigned as unexposed controls (n=6) bedded with control sand, or exposed calves (n=6) bedded with sand previously positive for M. bovis at a dairy farm. Bedding sand was cultured weekly. Nasal and ear swabs and sera were collected weekly, tracheal swabs were collected monthly, and by the end of the 105-d study, all calves were euthanized (n=10) or died (n=2). Sera were tested for M. bovis-specific antibody. Mycoplasma spp. culture was performed on nasal and ear swabs; culture and a PCR differentiating multiple Mycoplasma spp. were performed on postmortem samples of lung, retropharyngeal lymph node, and trachea from each calf. A complete necropsy also was performed. During 6 wk, mycoplasma concentration in exposed group sand was between 200 and 32,000 cfu/g. All 166 tracheal swabs, nasal and ear swabs, and postmortem tests from all calves were negative for mycoplasma. All 94 sera were negative for M. bovis-specific antibody. No gross pathology suggestive of mycoplasma disease was detected. The probability of mycoplasma detection, if an exposed calf had become infected 4 wk after exposure, ranged between 97 and 99% depending on time of exposure for individual calves. There was no evidence that sand bedding contaminated with M. bovis might serve as a source of transmission to naïve dairy calves.


title: ACE2 and TMPRSS2 are expressed on the human ocular surface, suggesting susceptibility to SARS-CoV-2 infection

text: Purpose Conjunctival signs and symptoms are observed in a subset of patients with COVID-19, and SARS-CoV-2 has been detected in tears, raising concerns regarding the eye both as a portal of entry and carrier of the virus. The purpose of this study was to determine whether ocular surface cells possess the key factors required for cellular susceptibility to SARS-CoV-2 entry/infection. Methods We analyzed human post-mortem eyes as well as surgical specimens for the expression of ACE2 (the receptor for SARS-CoV-2) and TMPRSS2, a cell surface-associated protease that facilitates viral entry following binding of the viral spike protein to ACE2. Results Across all eye specimens, immunohistochemical analysis revealed expression of ACE2 in the conjunctiva, limbus, and cornea, with especially prominent staining in the superficial conjunctival and corneal epithelial surface. Surgical conjunctival specimens also showed expression of ACE2 in the conjunctival epithelium, especially prominent in the superficial epithelium, as well as the substantia propria. All eye and conjunctival specimens also expressed TMPRSS2. Finally, western blot analysis of protein lysates from human corneal epithelium obtained during refractive surgery confirmed expression of ACE2 and TMPRSS2. Conclusions Together, these results indicate that ocular surface cells including conjunctiva are susceptible to infection by SARS-CoV-2, and could therefore serve as a portal of entry as well as a reservoir for person-to-person transmission of this virus. This highlights the importance of safety practices including face masks and ocular contact precautions in preventing the spread of COVID-19 disease.


Electron microscopy of SARS-CoV-2: a challenging task – Authors' reply


title: Tissue-Specific Amino Acid Transporter Partners ACE2 and Collectrin Differentially Interact With Hartnup Mutations

text: Background & Aims Hartnup amino acid transporter B0AT1 (SLC6A19) is the major luminal sodium-dependent neutral amino acid transporter of small intestine and kidney proximal tubule. The expression of B0AT1 in kidney was recently shown to depend on its association with collectrin (Tmem27), a protein homologous to the membrane-anchoring domain of angiotensin-converting enzyme (ACE) 2. Methods Because collectrin is almost absent from small intestine, we tested the hypothesis that it is ACE2 that interacts with B0AT1 in enterocytes. Furthermore, because B0AT1 expression depends on an associated protein, we tested the hypothesis that Hartnup-causing B0AT1 mutations differentially impact on B0AT1 interaction with intestinal and kidney accessory proteins. Results Immunofluorescence, coimmunoprecipitation, and functional experiments using wild-type and ace2-null mice showed that expression of B0AT1 in small intestine critically depends on ACE2. Coexpressing new and previously identified Hartnup disorder–causing missense mutations of B0AT1 with either collectrin or ACE2 in Xenopus laevis oocytes showed that the high-frequency D173N and the newly identified P265L mutant B0AT1 transporters can still be activated by ACE2 but not collectrin coexpression. In contrast, the human A69T and R240Q B0AT1 mutants cannot be activated by either of the associated proteins, although they function as wild-type B0AT1 when expressed alone. Conclusions We thus show that ACE2 is necessary for the expression of the Hartnup transporter in intestine and suggest that the differential functional association of mutant B0AT1 transporters with ACE2 and collectrin in intestine and kidney, respectively, participates in the phenotypic heterogeneity of human Hartnup disorder.


title: Síndrome respiratorio agudo grave, gripe aviar e infección por metapneumovirus humano

text: Los virus respiratorios fueron descubiertos progresivamente a partir del año 1950 gracias a la posibilidad de aislarlos en cultivos celulares. Los últimos fueron los coronavirus en la década de los años sesenta. No hubo más descubrimientos hasta 2001 con el metapneumovirus humano asociado a brotes de bronquiolitis en niños. Un año después, en noviembre de 2002, apareció el síndrome respiratorio agudo grave (SRAG) definido como una neumonía atípica, al que se asoció un nuevo virus como agente etiológico perteneciente a la familia de los coronavirus. En 2004 se descubrió otro coronavirus (CoV-NL63) y en 2005 se ha publicado el descubrimiento de un tercer coronavirus humano (CoV-HKU1). Además, varios subtipos del virus de la gripe A, que hasta ahora se pensaba que eran patógenos exclusivos de aves, se han transmitido directamente al ser humano. Si la infección respiratoria ha sido importante para el ser humano desde hace siglos, el conocimiento de nuevos virus asociados a ella se presenta en el siglo XXI como un importante campo de trabajo. Beginning in the 1950s respiratory viruses have been gradually discovered by isolation in cell cultures The last were the coronaviruses in the 1960s. No new respiratory viruses were discovered until 2001 when human metapneumovirus was found in respiratory specimens from children with bronchiolitis. A year later, in November 2002, severe acute respiratory syndrome (SARS) suddenly appeared as atypical pneumonia. A novel virus belonging to the Coronaviridae family was found to be a cause of this infection. In 2004, a second coronavirus was discovered (CoV-NL63) and in 2005 a third new coronavirus was described (CoV-HKU1). In addition, several subtypes of the influenza A virus, previously known to infect only poultry and wild birds, were recently found to have been directly transmitted to humans. Respiratory infection has been a considerable problem for humans for centuries. Now, in the 21st century, with new associated viruses continuously emerging, it remains an important field for work.


title: Impact of rotavirus vaccine on rotavirus genotypes and caliciviruses circulating in French cattle

text: Group A rotaviruses are a leading cause of neonatal calf diarrhoea worldwide and prevention of this disease includes vaccination against these viruses. In order to highlight the potential selection of rotavirus genotypes due to immune pressure driven by vaccination, the aim of this study was to compare group A rotavirus genotypes circulating in French diarrhoeic calves in rotavirus vaccinated herds (G6P[5] vaccine) with those in non-vaccinated herds during one calving season in 2010. This study showed a high prevalence of rotavirus in both groups with no significant difference between the two. No significant differences regarding G, P and G/P rotavirus genotype distribution between the two groups were observed, with G6, P[5] and G6P[5] genotypes being by far the most prevalent. Moreover, sequence analyses of the VP7 and VP4 partial coding genes of the G6P[5] strains from this study did not allow us to distinguish them according to their origin. This study also showed that other pathogens responsible for calf diarrhoea, such as genogroup III noroviruses and neboviruses, were not more frequently associated with calf diarrhoea in vaccinated herds. Altogether, these results suggest that the studied vaccine did not promote the emergence of rotavirus genotypes or variants different from those of the vaccine or other viruses responsible for calf diarrhoea, such as caliciviruses.


title: The viral innate immune antagonism and an alternative vaccine design for PRRS virus

text: Abstract Porcine reproductive and respiratory syndrome (PRRS) remains one of the most economically significant diseases in the swine industry worldwide. The current vaccines are less satisfactory to confer protections from heterologous infections and long-term persistence, and the need for better vaccines are urgent. The immunological hallmarks in PRRSV-infected pigs include the unusually poor production of type I interferons (IFNs-α/β) and the aberrant and delayed adaptive immune responses, indicating that PRRSV has the ability to suppress both innate and adaptive immune responses in the host. Type I IFNs are the potent antiviral cytokines and recent studies reveal their pleiotropic functions in the priming of expansion and maturation of adaptive immunity. Thus, IFN antagonism-negative PRRSV is hypothesized to be attenuated and to build effective and broad- spectrum innate and adaptive immune responses in pigs. Such vaccines are promising alternatives to traditional vaccines for PRRSV.


title: Household Transmission of Human Adenovirus Type 55 in Case of Fatal Acute Respiratory Disease

text: We identified a case of fatal acute respiratory disease from household transmission of human adenovirus type 55 (HAdV-55) in Anhui Province, China. Computed tomography showed severe pneumonia. Comparative genomic analysis of HAdV-55 indicated the virus possibly originated in Shanxi Province, China. More attention should be paid to highly contagious HAdV-55.


Heart failure related hospitalisation and management during COVID‐19 pandemic: are we ready to reflect? – REPLY


Role of Mask/Respirator Protection Against SARS-CoV-2


title: Enhancing Citizens Response to Out-of-Hospital Cardiac Arrest: A Systematic Review of Mobile-Phone Systems to Alert Citizens as First Responders

text: Abstract Introduction Involving laypersons in response to out-of-hospital cardiac arrest through mobile-phone technology is becoming widespread in numerous countries, and different solutions were developed. We performed a systematic review on the impact of alerting citizens as first responders and to provide an overview of different strategies and technologies used. Methods We searched electronic databases up to October 2019. Eligible studies described systems to alert citizens first responders to out-of-hospital cardiac arrest through text messages or apps. We analysed the implementation and performance of these systems and their impact on patients’ outcomes. Results We included 28 manuscripts describing 12 different systems. The first text message system was implemented in 2006 and the first app in 2010. First responders accepted to intervene in median (interquartile) 28.7% (27-29%) of alerts and reached the scene after 4.6 (4.4-5.5) minutes for performing CPR. First responders arrived before ambulance, started CPR and attached a defibrillator in 47% (34-58%), 24% (23-27%) and 9% (6-14%) of cases, respectively. Pooled analysis showed that first responders activation increased layperson-CPR rates (1463/2292 [63.8%] in the intervention group vs. 1094/1989 [55.0%] in the control group; OR=1.70; 95% CI, 1.11–2.60; p=0.01) and survival to hospital discharge or at 30 days (327/2273 [14.4%] vs. 184/1955 [9.4%]; OR=1.51; 95% CI, 1.24–1.84; p<0.001). Conclusions Alerting citizens as first responders in case of out-of-hospital cardiac arrest may reduce the intervention-free time and improve patients’ outcomes.


docid: usrpodjx

title: Pathogenesis of Lassa Fever

text: Lassa virus, an Old World arenavirus (family Arenaviridae), is the etiological agent of Lassa fever, a severe human disease that is reported in more than 100,000 patients annually in the endemic regions of West Africa with mortality rates for hospitalized patients varying between 5-10%. Currently, there are no approved vaccines against Lassa fever for use in humans. Here, we review the published literature on the life cycle of Lassa virus with the specific focus put on Lassa fever pathogenesis in humans and relevant animal models. Advancing knowledge significantly improves our understanding of Lassa virus biology, as well as of the mechanisms that allow the virus to evade the host’s immune system. However, further investigations are required in order to design improved diagnostic tools, an effective vaccine, and therapeutic agents.


title: Fiebre chikungunya - Una nueva amenaza global

text: Resumen Las epidemias causadas, entre otros, por los virus Ébola, Marburgo, Nipah, Lassa, coronavirus, virus del Nilo Occidental, virus de Saint Louis, virus de la inmunodeficiencia humana, dengue, fiebre amarilla y fiebre hemorrágica venezolana han puesto sobre el tapete el riesgo que estos agentes representan para la salud pública global. Entre las nuevas amenazas destaca el virus chikungunya, que ha extendido rápidamente su área endémica desde regiones remotas de África hacia la cuenca del océano Índico y el Pacífico Oriental, causando importantes epidemias en África, Asia, islas del Índico y Europa Occidental, llegando a establecerse recientemente en islas del Caribe. Debido a su comportamiento dual endémico y epidémico, a sus propiedades virológicas y a la presencia global de sus vectores, este virus entraña el riesgo de causar grandes epidemias e instalarse en el territorio continental de las Américas a partir de la introducción de casos importados y a la circulación local vista en la región caribeña. Se revisan las principales características epidemiológicas y clínicas de la fiebre chikungunya y el riesgo de introducción de esta enfermedad en las Américas, enfatizando el rol de la vigilancia y la lucha contra los mosquitos en su prevención. Abstract The recent onset of epidemics caused by viruses such as Ebola, Marburg, Nipah, Lassa, coronavirus, West-Nile encephalitis, Saint Louis encephalitis, human immunodeficiency virus, dengue, yellow fever and Venezuelan hemorrhagic fever alerts about the risk these agents represent for the global health. Chikungunya virus represents a new threat. Surged from remote African regions, this virus has become endemic in the Indic ocean basin, the Indian subcontinent and the southeast of Asia, causing serious epidemics in Africa, Indic Ocean Islands, Asia and Europe. Due to their epidemiological and biological features and the global presence of their vectors, chikungunya represents a serious menace and could become endemic in the Americas. Although chikungunya infection has a low mortality rate, its high attack ratio may collapse the health system during epidemics affecting a sensitive population. In this paper, we review the clinical and epidemiological features of chikungunya fever as well as the risk of its introduction into the Americas. We remark the importance of the epidemiological control and mosquitoes fighting in order to prevent this disease from being introduced into the Americas.


title: Electrophoretic separations on microfluidic chips

text: Abstract This review presents a brief outline and novel developments of electrophoretic separation in microfluidic chips. Distinct characteristics of microchip electrophoresis (MCE) are discussed first, in which sample injection plug, joule heat, channel turn, surface adsorption and modification are introduced, and some successful strategies and recognized conclusions are also included. Important achievements of microfluidic electrophoresis separation in small molecules, DNA and protein are then summarized. This review is aimed at researchers, who are interested in MCE and want to adopt MCE as a functional unit in their integrated microsystems.


title: Modelling can only tell us so much: politics explains the rest Adam Kucharski

text: Unknown


Intervention précoce avec un protocole d’EMDR dans un centre de dépistage du COVID-19


title: Molecular characterization of astrovirus infection in children with diarrhea in Beijing, 2005–2007

text: Human astroviruses (HAstVs) have been recognized as one of the major causes of acute gastroenteritis in children. To provide more insight into the prevalence of HAstV gastroenteritis in China, 664 fecal samples were collected from children affected with acute gastroenteritis in Beijing from March 2005 to November 2007. The samples were analyzed genetically. All eight serotypes (genotypes) of HAstVs were screened using RT‐PCR assays targeting the ORF2 region in the study. The assays detected HAstVs in 52 (7.8%) of the patients, with HAstV‐1 (50/52) being the dominant genotype during the study period. Two minor genotypes, HAstV‐6 and HAstV‐3, were also detected. Partial sequencing of the 50 HAstV‐1 strains showed that the homology of the nucleotide sequence of the ORF1a region between these strains was 88.4–100%, whereas the homology of the amino acid sequences was 95.6–100%. In the ORF2 partial region, the nucleotide identities ranged from 91.5% to 100%, and amino acid identities ranged from 97.3% to 100%. The identity of the whole genome sequence between four randomly examined HAstV‐1 strains was 91–99%. No recombination events were observed in HAstVs in this study. The findings of this study will provide baseline data for HAstVs surveillance and control. J. Med. Virol. 82:415–423, 2010. © 2010 Wiley‐Liss, Inc.


docid: syeavper

title: Murine hepatitis virus nsp4 N258T mutants are not temperature-sensitive

text: Abstract Coronavirus replicase nsp4 is critical for virus-induced membrane modifications. An nsp4 mutant (N258T) of murine hepatitis virus (MHV) has been reported to be temperature-sensitive (ts) and to alter membrane targeting. We engineered and recovered all four possible codon variants of N258T in the cloned MHV-A59 background. All mutant viruses demonstrated impaired replication compared to wildtype MHV, but no nsp4 N258T mutant virus was ts, and all variants colocalized with viral protein markers for replication complexes, but not with markers for mitochondria. This study emphasizes that complete genome sequencing may be necessary, even with directed and confirmed reverse genetic mutants.


title: Virucidal action of sore throat lozenges against respiratory viruses parainfluenza type 3 and cytomegalovirus

text: Abstract Most respiratory tract infections are self-limiting and caused by viruses, and do not warrant antibiotic treatment. Despite this, patients with respiratory tract infections often receive antibiotics, fuelling the rise of antibiotic resistance. Therefore, there is a need to encourage patients to try alternative non-antibiotic therapies, which ideally treat the symptoms and the cause. Lozenges containing amylmetacresol and 2,4-dichlorobenzyl alcohol (AMC/DCBA lozenges) as well as lozenges containing hexylresorcinol have been shown to provide effective symptomatic relief for sore throat. In this study, we investigated whether these lozenges also have virucidal effects in vitro against two viruses associated with respiratory tract infections, parainfluenza virus type 3 and cytomegalovirus. Both viruses were incubated with AMC/DCBA lozenge, placebo lozenge or the active ingredients (AMC/DCBA) as free substances, and parainfluenza virus type 3 was incubated with hexylresorcinol lozenge, placebo lozenge or hexylresorcinol as a free substance. Virucidal effects were observed with the active lozenges and the active ingredients as free substances against both parainfluenza virus type 3 and cytomegalovirus. Mean reductions in viral titre were significantly greater compared with placebo lozenge and peak effects were observed for the shortest incubation time, 1min. These findings suggest that AMC/DCBA lozenge and hexylresorcinol lozenge have the potential to have local antiviral effects in patients with sore throat due to viral respiratory tract infections. Use of such over-the-counter treatments for self-limiting respiratory tract infections may satisfy patients’ desire for an anti-infective medication and reduce the demand for antibiotics.


title: First respiratory transmitted food borne outbreak?

text: Abstract The world is faced with a remarkable coronavirus outbreak with epicentre in Wuhan, China. Altogether 40554 cases have been confirmed globally with novel coronavirus (SARS-CoV-2) until February 10, 2020. Rigorous surveillance in other countries is required to prevent further global expansion of the outbreak, but resolving the exact mechanism of the initial transmission events is crucial. Most initial cases had visited Huanan South Seafood Market in Wuhan selling also various exotic live animals. Based on the limited initial human-to-human transmission and timely clustering of cases in Huanan market among elderly men, coupled with knowledge that coronaviruses are derived from animals and relationship of SARS-CoV-2 to bat coronavirus, zoonotic transmission in the first instance is probable. To target the actions, similar epidemiological actions to human cases are needed with animal or food exposures. According to current information, an exceptionally wide contamination of seafood market might explain the initiation of the SARS-CoV-2 outbreak. Seafood tanks, air contamination by live animals or rodents are possibilities, but sold animals normally come from various sources. The mode of transmission may become clearer in future: usually in outbreak investigations, hindsight is easy, but for now information about the initial source of this outbreak is limited.


title: Modulation of nasopharyngeal innate defenses by viral coinfection predisposes individuals to experimental pneumococcal carriage

text: Increased nasopharyngeal colonization density has been associated with pneumonia. We used experimental human pneumococcal carriage to investigate whether upper respiratory tract viral infection predisposes individuals to carriage. A total of 101 healthy subjects were screened for respiratory virus before pneumococcal intranasal challenge. Virus was associated with increased odds of colonization (75% virus positive became colonized vs. 46% virus-negative subjects; P=0.02). Nasal Factor H (FH) levels were increased in virus-positive subjects and were associated with increased colonization density. Using an in vitro epithelial model we explored the impact of increased mucosal FH in the context of coinfection. Epithelial inflammation and FH binding resulted in increased pneumococcal adherence to the epithelium. Binding was partially blocked by antibodies targeting the FH-binding protein Pneumococcal surface protein C (PspC). PspC epitope mapping revealed individuals lacked antibodies against the FH binding region. We propose that FH binding to PspC in vivo masks this binding site, enabling FH to facilitate pneumococcal/epithelial attachment during viral infection despite the presence of anti-PspC antibodies. We propose that a PspC-based vaccine lacking binding to FH could reduce pneumococcal colonization, and may have enhanced protection in those with underlying viral infection.


title: Epidemiology of Human Respiratory Viruses in Children with Acute Respiratory Tract Infections in Jinan, China

text: The viral etiologies of UTRIs and LTRIs in children in Jinan city were investigated between July 2009 and June 2010. Nasal and throat swabs were collected from 397 children with URTIs and bronchoalveolar lavage fluid specimens were collected from 323 children with LRTIs. RT-PCR/PCR was used to examine all samples for IFV, PIV, RSV, RV, hMPV, HBoV, CoV, ADV, RSV, and EV. Viral pathogens were detected in 47.10% of URTI samples and 66.57% samples, and the incidence of viral coinfection was 5.29% and 21.05%, respectively. IFV was the most common virus in URTIs, with a detection rate of 19.40%, followed by PIV (10.83%), RV (10.58%), and EV (6.30%). For LRTIs, PIV and RV were both detected in 27% of samples, followed by RSV (9.91%), HBoV (8.36%), IFV (5.57%), and hMPV (5.57%). RSV and HBoV were more prevalent in the youngest children of no more than six months. Meanwhile, RV, PIV, and RSV were the most frequent viruses combined with bacterial pathogens in LRTIs. In conclusion, the spectrum of respiratory virus infections in URTIs and LRTIs differed in terms of the most common pathogens, seasonal distribution, and coinfection rate.


title: The past, present, and future of consumer research

text: In this article, we document the evolution of research trends (concepts, methods, and aims) within the field of consumer behavior, from the time of its early development to the present day, as a multidisciplinary area of research within marketing. We describe current changes in retailing and real-world consumption and offer suggestions on how to use observations of consumption phenomena to generate new and interesting consumer behavior research questions. Consumption continues to change with technological advancements and shifts in consumers’ values and goals. We cannot know the exact shape of things to come, but we polled a sample of leading scholars and summarize their predictions on where the field may be headed in the next twenty years.


title: Contrasted patterns of variation and evolutionary convergence at the antiviral OAS1 gene in old world primates

text: The oligoadenylate synthetase 1 (OAS1) enzyme acts as an innate sensor of viral infection and plays a major role in the defense against a wide diversity of viruses. Polymorphisms at OAS1 have been shown to correlate with differential susceptibility to several infections of great public health significance, including hepatitis C virus, SARS coronavirus, and West Nile virus. Population genetics analyses in hominoids have revealed interesting evolutionary patterns. In Central African chimpanzee, OAS1 has evolved under long-term balancing selection, resulting in the persistence of polymorphisms since the origin of hominoids, whereas human populations have acquired and retained OAS1 alleles from Neanderthal and Denisovan origin. We decided to further investigate the evolution of OAS1 in primates by characterizing intra-specific variation in four species commonly used as models in infectious disease research: the rhesus macaque, the cynomolgus macaque, the olive baboon, and the Guinea baboon. In baboons, OAS1 harbors a very low level of variation. In contrast, OAS1 in macaques exhibits a level of polymorphism far greater than the genomic average, which is consistent with the action of balancing selection. The region of the enzyme that directly interacts with viral RNA, the RNA-binding domain, contains a number of polymorphisms likely to affect the RNA-binding affinity of OAS1. This strongly suggests that pathogen-driven balancing selection acting on the RNA-binding domain of OAS1 is maintaining variation at this locus. Interestingly, we found that a number of polymorphisms involved in RNA-binding were shared between macaques and chimpanzees. This represents an unusual case of convergent polymorphism.


Coronavirus-Pandemie: So werden die Leistungen am Patienten vergütet: Wie Sie an das extrabudgetäre Honorar kommen


title: Nsp1 proteins of group I and SARS coronaviruses share structural and functional similarities

text: Abstract The nsp1 protein of the highly pathogenic SARS coronavirus suppresses host protein synthesis, including genes involved in the innate immune system. A bioinformatic analysis revealed that the nsp1 proteins of group I and SARS coronaviruses have similar structures. Nsp1 proteins of group I coronaviruses interacted with host ribosomal 40S subunit and did not inhibit IRF-3 activation. However, synthesis of host immune and non-immune proteins was inhibited by nsp1 proteins at both transcriptional and translational levels, similar to SARS coronavirus nsp1. These results indicate that different coronaviruses might employ the same nsp1 mechanism to antagonize host innate immunity and cell proliferation. However, nsp1 may not be the key determinant of viral pathogenicity, or the factor used by the SARS coronavirus to evade host innate immunity.


Interaction of Biologically-Relevant Peptides with Membrane Model Systems


title: Arthropods as vectors of transmissible diseases in Spain

text: Abstract Different aspects related to globalization together with the great capacity of the arthropod vectors to adapt to a changing world favour the emergence and reemergence of numerous infectious diseases transmitted by them. Diptera (mosquitoes and sandflies), ticks, fleas and lice, among others, cause a wide spectrum of diseases with relevance in public health. Herein, arthropod-borne disease are reviewed, with special emphasis on the existing risk to contract them in Spain according to different parameters, such as the presence of arthropod and the circulation or the possible circulation of the causative agents.


title: Application of Genetically Engineered Pigs in Biomedical Research

text: Progress in genetic engineering over the past few decades has made it possible to develop methods that have led to the production of transgenic animals. The development of transgenesis has created new directions in research and possibilities for its practical application. Generating transgenic animal species is not only aimed towards accelerating traditional breeding programs and improving animal health and the quality of animal products for consumption but can also be used in biomedicine. Animal studies are conducted to develop models used in gene function and regulation research and the genetic determinants of certain human diseases. Another direction of research, described in this review, focuses on the use of transgenic animals as a source of high-quality biopharmaceuticals, such as recombinant proteins. The further aspect discussed is the use of genetically modified animals as a source of cells, tissues, and organs for transplantation into human recipients, i.e., xenotransplantation. Numerous studies have shown that the pig (Sus scrofa domestica) is the most suitable species both as a research model for human diseases and as an optimal organ donor for xenotransplantation. Short pregnancy, short generation interval, and high litter size make the production of transgenic pigs less time-consuming in comparison with other livestock species This review describes genetically modified pigs used for biomedical research and the future challenges and perspectives for the use of the swine animal models.


title: A novel cognitive interpretation of breast cancer thermography with complementary learning fuzzy neural memory structure

text: Abstract Early detection of breast cancer is the key to improve survival rate. Thermogram is a promising front-line screening tool as it is able to warn women of breast cancer up to 10 years in advance. However, analysis and interpretation of thermogram are heavily dependent on the analysts, which may be inconsistent and error-prone. In order to boost the accuracy of preliminary screening using thermogram without incurring additional financial burden, Complementary Learning Fuzzy Neural Network (CLFNN), FALCON-AART is proposed as the Computer-Assisted Intervention (CAI) tool for thermogram analysis. CLFNN is a neuroscience-inspired technique that provides intuitive fuzzy rules, human-like reasoning, and good classification performance. Confluence of thermogram and CLFNN offers a promising tool for fighting breast cancer.


title: 1,2,3,4,6-Penta-O-galloylglucose within Galla Chinensis Inhibits Human LDH-A and Attenuates Cell Proliferation in MDA-MB-231 Breast Cancer Cells

text: A characteristic feature of aggressive malignancy is the overexpression of lactic acid dehydrogenase- (LDH-) A, concomitant to pericellular accumulation of lactate. In a recent high-throughput screening, we identified Rhus chinensis (Mill.) gallnut (RCG) (also known as Galla Chinensis) extract as a potent (IC(50) < 1 µg/mL) inhibitor of human LDH-A (hLDH-A). In this study, through bioactivity guided fractionation of the crude extract, the data demonstrate that penta-1,2,3,4,6-O-galloyl-β-D-glucose (PGG) was a primary constituent responsible for hLDH-A inhibition, present at ~9.95 ± 0.34% dry weight. Theoretical molecular docking studies of hLDH-A indicate that PGG acts through competitive binding at the NADH cofactor site, effects confirmed by functional enzyme studies where the IC(50) = 27.32 nM was reversed with increasing concentration of NADH. Moreover, we confirm protein expression of hLDH-A in MDA-231 human breast carcinoma cells and show that PGG was toxic (LC(50) = 94.18 µM), parallel to attenuated lactic acid production (IC(50) = 97.81 µM). In a 72-hour cell proliferation assay, PGG was found to be a potent cytostatic agent with ability to halt cell division (IC(50) = 1.2 µM) relative to paclitaxel (IC(50) < 100 nM). In summary, these findings demonstrate that PGG is a potent hLDH-A inhibitor with significant capacity to halt proliferation of human breast cancer cells.


title: Generation and Analysis of Novel Plant-Derived Antibody-Based Therapeutic Molecules against West Nile Virus

text: Previously, our group engineered a plant-derived monoclonal antibody (MAb) (pHu-E16) that efficiently treated West Nile virus (WNV) infection in mice. In this study, we developed several pHu-E16 variants to improve its efficacy. These variants included a single-chain variable fragment (scFv) of pHu-E16 fused to the heavy chain (HC) constant domains (C(H) (1-3)) of human IgG (pHu-E16scFv-C(H) (1-3)) and a tetravalent molecule (Tetra pHu-E16) assembled from pHu-E16scFv-C(H) (1-3) with a second pHu-E16scFv fused to the light chain (LC) constant region. pHu-E16scFv-C(H) (1-3) and Tetra pHu-E16 were efficiently expressed and assembled in plants. To assess the impact of differences in N-linked glycosylation on pHu-E16 variant assembly and function, we expressed additional pHu-E16 variants with various combinations of HC and LC components. Our study revealed that proper pairing of HC and LC was essential for the complete N-glycan processing of antibodies in both plant and animal cells. Associated with their distinct N-glycoforms, pHu-E16, pHu-E16scFv-C(H) (1-3) and Tetra pHu-E16 exhibited differential binding to C1q and specific Fcγ receptors (FcγR). Notably, none of the plant-derived Hu-E16 variants showed antibody-dependent enhancement (ADE) activity in CD32A(+) human cells, suggesting the potential of plant-produced antibodies to minimize the adverse effect of ADE. Importantly, all plant-derived MAb variants exhibited at least equivalent in vitro neutralization and in vivo protection in mice compared to mammalian cell-produced Hu-E16. This study demonstrates the capacity of plants to express and assemble a large, complex and functional IgG-like tetravalent mAb variant and also provides insight into the relationship between MAb N-glycosylation, FcγR and C1q binding, and ADE. These new insights may allow the development of safer and cost effective MAb-based therapeutics for flaviviruses, and possibly other pathogens.


UGANDA: Strict Covid‐19 Measures


title: Ellagic Acid, Kaempferol, and Quercetin from Acacia nilotica: Promising Combined Drug With Multiple Mechanisms of Action

text: The pharmacological activity of Acacia nilotica’s phytochemical constituents was confirmed with evidence-based studies, but the determination of exact targets that they bind and the mechanism of action were not done; consequently, we aim to identify the exact targets that are responsible for the pharmacological activity via the computational methods. Furthermore, we aim to predict the pharmacokinetics (ADME) properties and the safety profile in order to identify the best drug candidates. To achieve those goals, various computational methods were used including the ligand-based virtual screening and molecular docking. Moreover, pkCSM and SwissADME web servers were used for the prediction of pharmacokinetics and safety. The total number of the investigated compounds and targets was 25 and 61, respectively. According to the results, the pharmacological activity was attributed to the interaction with essential targets. Ellagic acid, Kaempferol, and Quercetin were the best A. nilotica’s phytochemical constituents that contribute to the therapeutic activities, were non-toxic as well as non-carcinogen. The administration of Ellagic acid, Kaempferol, and Quercetin as combined drug via the novel drug delivery systems will be a valuable therapeutic choice for the treatment of recent diseases attacking the public health including cancer, multidrug-resistant bacterial infections, diabetes mellitus, and chronic inflammatory systemic disease.


title: Equine Coronavirus-Associated Colitis in Horses: A Retrospective Study

text: Abstract Equine coronavirus (ECoV) is a known cause of fever, anorexia, and lethargy in adult horses. Although there are multiple reports of ECoV outbreaks, less is known about the clinical presentation of individual horses during a nonoutbreak situation. The purpose of this study was to describe the clinical presentation of horses diagnosed with ECoV infection that were not associated with an outbreak. Medical records of all horses admitted to Washington State University, Veterinary Teaching Hospital, during an 8-year period were reviewed (2010–2018). The five horses included in this study were older than 1 year of age, were diagnosed with colitis, tested positive for ECoV using real-time polymerase chain reaction, and were negative to other enteric pathogens. Interestingly, 4 of 5 horses had moderate to severe diarrhea, 3 had abnormal large colon ultrasonography, 2 had transient ventricular tachycardia and 2 had clinicopathologic evidence of liver dysfunction. ECoV should be included as a differential diagnosis for individual horses presenting with anorexia, fever, lethargy, and colitis. Early identification of ECoV cases is key to implement appropriate biosecurity measures to prevent the potential spread of this disease.


title: Estimating the effects of asymptomatic and imported patients on COVID‐19 epidemic using mathematical modeling

text: The epidemic of Coronavirus Disease 2019 has been a serious threat to public health worldwide. Data from 23 January to 31 March at Jiangsu and Anhui provinces in China were collected. We developed an adjusted model with two novel features: the asymptomatic population and threshold behavior in recovery. Unbiased parameter estimation identified faithful model fitting. Our model predicted that the epidemic for asymptomatic patients (ASP) was similar in both provinces. The latent periods and outbreak sizes are extremely sensitive to strongly controlled interventions such as isolation and quarantine for both asymptomatic and imported cases. We predicted that ASP serve as a more severe factor with faster outbreaks and larger outbreak sizes compared with imported patients. Therefore, we argued that the currently strict interventions should be continuously implemented, and unraveling the asymptomatic pool is critically important before preventive strategy such as vaccines.


From the Editor's desk


title: Immediate psychological distress in quarantined patients with COVID-19 and its association with peripheral inflammation: a mixed-method study

text: Since the end of 2019, Corona Virus Disease 2019 (COVID-19) has been the cause of a worldwide pandemic. The mental status of patients with COVID-19 who have been quarantined and the interactions between their psychological distress and physiological levels of inflammation have yet to be analyzed. Using a mixed-method triangulation design (QUAN + QUAL), this study investigated and compared the mental status and inflammatory markers of 103 patients who, while hospitalized with mild symptoms, tested positive with COVID-19 and 103 matched controls that were COVID-19 negative. The severity of depression, anxiety, and post-traumatic stress symptoms (PTSS) was measured via an on-line survey. Using a convenience sampling technique, qualitative data were collected until the point of data saturation. In addition, a semi-structured interview was conducted among five patients with COVID-19. Peripheral inflammatory markers were also collected in patients, both at baseline and within ± three days of completing the on-line survey. Results revealed that COVID-19 patients, when compared to non-COVID controls, manifested higher levels of depression (P < 0.001), anxiety (P < 0.001), and post-traumatic stress symptoms (P < 0.001). A gender effect was observed in the score of “Perceived Helplessness”, the subscale of PSS-10, with female patients showing higher scores compared to male patients (Z = 2.56, P = 0.010), female (Z = 2.37, P = 0.018) and male controls (Z = 2.87, P = 0.004). Levels of CRP, a peripheral inflammatory indicator, correlated positively with the PHQ-9 total score (R = .37, P = 0.003, Spearman’s correlation) of patients who presented symptoms of depression. Moreover, the change of CRP level from baseline inversely correlated with the PHQ-9 total score (R = -0.31, P = 0.002), indicative of improvement of depression symptoms. Qualitative analysis revealed similar results with respect to patient reports of negative feelings, including fear, guilt, and helplessness. Stigma and uncertainty of viral disease progression were two main concerns expressed by COVID-19 patients. Our results indicate that significant psychological distress was experienced by hospitalized COVID-19 patients and that levels of depressive features may be related to the inflammation markers in these patients. Thus, we recommend that necessary measures should be provided to address depression and other psychiatric symptoms for COVID-19 patients and attention should be paid to patient perceived stigma and coping strategies when delivering psychological interventions.


title: A SARS-CoV-2 vaccine candidate: In silico cloning and validation

text: SARS-CoV-2 is spreading globally at a rapid pace. To contain its spread and prevent further fatalities, the development of a vaccine against SARS-CoV-2 is an urgent prerequisite. Thus, in this article, by utilizing the in silico approach, a vaccine candidate for SARS-CoV-2 has been proposed. Moreover, the effectiveness and safety measures of our proposed epitopic vaccine candidate have been evaluated by in silico tools and servers (AllerTOP and AllergenFP servers). We observed that the vaccine candidate has no allergenicity and successfully combined with Toll-like receptor (TLR) protein to elicit an inflammatory immune response. Stable, functional mobility of the vaccine-TLR protein binding interface was confirmed by the Normal Mode Analysis. The in silico cloning model demonstrated the efficacy of the construct vaccine along with the identified epitopes against SARS-CoV-2. Taken together, our proposed in silico vaccine candidate has potent efficacy against COVID-19 infection, and successive research work might validate its effectiveness in in vitro and in vivo models.


SARS‐CoV‐2 and the Liver: Considerations in Hepatitis B and Hepatitis C Infections


title: Chapter 27 Sphenisciformes, Gaviiformes, Podicipediformes, Procellariiformes, and Pelecaniformes

text: Abstract Penguins are flightless seabirds with unique anatomy. Although susceptible to a wide range of diseases, aspergillosis and avian malaria dominate captive mortalities, whereas starvation impacts free-ranging colonies. Gastrointestinal foreign bodies, pododermatitis, drug and heavy metal toxicities are relevant in captivity; oil and algal biotoxicities in the wild. Arthropod-borne, pox-, and herpesviruses are significant for captive and free-ranging populations. Important bacterial diseases include salmonellosis, clostridiosis, and the polymicrobial contribution to penguin diphtheria. Free-ranging populations frequently harbor metazoan parasites but avian malaria is the most clinically important parasitic disease. Many Pelecaniformes, Gaviiformes, Podicipediformes, and Procellariiformes are pelagic species that congregate periodically in nesting colonies or during migration. For free-ranging pelagic species, information derives from infrequent opportunistic screening as sentinels of ocean health and pathogen circulation, and mass mortality events. Birds in captive populations, whose life history differs dramatically, are sparsely represented. Nutritional stress, infectious disease, and toxins contribute to morbidity in congregating birds. Adverse anthropogenic influences (population growth, climate change, environmental pollution, and intensive fishing) pose conservation threats.


title: Whither vaccines?

text: Summary Currently used vaccines have had major effects on eliminating common infections, largely by duplicating the immune responses induced by natural infections. Now vaccinology faces more complex problems, such as waning antibody, immunosenescence, evasion of immunity by the pathogen, deviation of immunity by the microbiome, induction of inhibitory responses, and complexity of the antigens required for protection. Fortunately, vaccine development is now incorporating knowledge from immunology, structural biology, systems biology and synthetic chemistry to meet these challenges. In addition, international organisations are developing new funding and licensing pathways for vaccines aimed at pathogens with epidemic potential that emerge from tropical areas.


title: Effects of distribution of infection rate on epidemic models

text: A goal of many epidemic models is to compute the outcome of the epidemics from the observed infected early dynamics. However, often, the total number of infected individuals at the end of the epidemics is much lower than predicted from the early dynamics. This discrepancy is argued to result from human intervention or nonlinear dynamics not incorporated in standard models. We show that when variability in infection rates is included in standard susciptible-infected-susceptible ([Formula: see text]) and susceptible-infected-recovered ([Formula: see text]) models the total number of infected individuals in the late dynamics can be orders lower than predicted from the early dynamics. This discrepancy holds for [Formula: see text] and [Formula: see text] models, where the assumption that all individuals have the same sensitivity is eliminated. In contrast with network models, fixed partnerships are not assumed. We derive a moment closure scheme capturing the distribution of sensitivities. We find that the shape of the sensitivity distribution does not affect [Formula: see text] or the number of infected individuals in the early phases of the epidemics. However, a wide distribution of sensitivities reduces the total number of removed individuals in the [Formula: see text] model and the steady-state infected fraction in the [Formula: see text] model. The difference between the early and late dynamics implies that in order to extrapolate the expected effect of the epidemics from the initial phase of the epidemics, the rate of change in the average infectivity should be computed. These results are supported by a comparison of the theoretical model to the Ebola epidemics and by numerical simulation.


title: Bioinformatic prediction of potential T cell epitopes for SARS-Cov-2

text: To control and prevent the current COVID-19 pandemic, the development of novel vaccines is an emergent issue. In addition, we need to develop tools that can measure/monitor T-cell and B-cell responses to know how our immune system is responding to this deleterious virus. However, little information is currently available about the immune target epitopes of novel coronavirus (SARS-CoV-2) to induce host immune responses. Through a comprehensive bioinformatic screening of potential epitopes derived from the SARS-CoV-2 sequences for HLAs commonly present in the Japanese population, we identified 2013 and 1399 possible peptide epitopes that are likely to have the high affinity (<0.5%- and 2%-rank, respectively) to HLA class I and II molecules, respectively, that may induce CD8(+) and CD4(+) T-cell responses. These epitopes distributed across the structural (spike, envelope, membrane, and nucleocapsid proteins) and the nonstructural proteins (proteins corresponding to six open reading frames); however, we found several regions where high-affinity epitopes were significantly enriched. By comparing the sequences of these predicted T cell epitopes to the other coronaviruses, we identified 781 HLA-class I and 418 HLA-class II epitopes that have high homologies to SARS-CoV. To further select commonly-available epitopes that would be applicable to larger populations, we calculated population coverages based on the allele frequencies of HLA molecules, and found 2 HLA-class I epitopes covering 83.8% of the Japanese population. The findings in the current study provide us valuable information to design widely-available vaccine epitopes against SARS-CoV-2 and also provide the useful information for monitoring T-cell responses.


title: Individual Monitoring and Occupational Dose Record Management in China: History, Current Status and Perspectives

text: This review paper presents an overview of individual monitoring, as well as the national dose register and dose record management of radiation workers in China. Progress has recently been made on the individual monitoring of radiation workers. A critical analysis of current status and problems in individual monitoring is also presented and necessary future research on individual monitoring, such as the monitoring technology in the form of the ring dosimeters and eye lens dosimeters, is suggested.


title: Strong policies control the spread of COVID‐19 in China

text: OBJECTIVE: The coronavirus disease 2019 (COVID‐19) outbroke in Wuhan, Hubei Province, China, affecting more than 200 countries and regions. This study aimed to predict the development of the epidemic with specific interventional policies applied in China and evaluate their effectiveness. METHODS: COVID‐19 data of Hubei Province and the next five most affected provinces were collected from daily case reports of COVID‐19 on the Health Committee official website of these provinces. The number of current cases, defined as the number of confirmed cases minus the number of cured cases and those who have died, was examined in this study. A modified Susceptible‐Exposed‐Infectious‐ Removed (SEIR) model was used to assess the effects of interventional policies on the epidemic. In this study, January 28 was day zero of the model. RESULTS: The results of the modified SEIR model showed that the number of current cases in Hubei and Zhejiang provinces tended to be stabilized after 70 days and after 60 days in the four other provinces. The predicted number of current cases without policy intervention was shown to far exceed that with policy intervention. The estimated number of COVID‐19 cases in Hubei Province with policy intervention was predicted to peak at 51,222, whereas that without policy intervention was predicted to reach 157,721. CONCLUSION: Based on the results of the model, strong interventional policies were found to be vital components of epidemic control. Applying such policies is likely to shorten the duration of the epidemic and reduce the number of new cases. This article is protected by copyright. All rights reserved.


title: Establishment of Vero E6 cell clones persistently infected with severe acute respiratory syndrome coronavirus

text: Abstract Little information is available on persistent infection of severe acute respiratory syndrome (SARS) coronavirus (CoV). In this study, we established persistent infection of SARS-CoV in the Vero E6 cell line. Acute infection of Vero E6 with SARS-CoV produced a lytic infection with characteristic rounding cytopathic effects (CPE) and the production of a large number of infectious particles in the culture fluid within 3 days post-infection. Upon subsequent culturing of the remaining adherent cells, the cells gradually proliferated and recovered normal morphology similar to that of the parental cells, and continued to produce large numbers of infectious viral particles during the observation period of 5 months. Among a total of 87 cell clones obtained from the persistently infected Vero E6, only four cell clones (named #13, #18, #21, and #34) were positive for viral RNA. Clones #13, #18, and #34 shifted to viral RNA-negative during subsequent cultures, while #21 continuously produced infectious particles at a high rate. The SARS-CoV receptor, angiotensin-converting enzyme 2, was almost completely down regulated from the cell surface of persistently infected cells. Western blot analysis as well as electron microscopy indicated that the ratios of spike to nucleocapsid protein in clone #21 as well as its parental persistently infected cells were lower than that in the cells in the acute phase of infection. These Vero E6 cells persistently infected with SARS-CoV may be useful for clarifying the mechanism of the persistent infection and also for elucidating the possible pathophysiologic significance of such long-term maintenance of this virus.