title: Chapter 1 Agents of Emerging Infectious Diseases

text: Abstract Dramatic improvements in the control of infectious diseases in developed countries owing to socioeconomic changes, vaccines, and antibiotics during the first seven decades of the 20th century led to the mistakened concept that infectious diseases would no longer be a concern. Since the declaration of victory in the war against infectious diseases in 1967, approximately 50 new disease agents have been identified. Nearly every type of etiologic agent and clinical manifestation have been involved including acute respiratory infections (e.g., H5N1 influenza A, SARS, hantaviral cardiopulmonary syndrome, and Legionnaires’ disease), central nervous system involvement (e.g., West Nile encephalitis, Nipah virus encephalitis, and prion diseases), enteric infections (e.g., Helicobacter pylori gastric and duodenal diseases, cryptosporidiosis, microsporidioses, and Shiga toxin diseases), systemic bacterial diseases (e.g., Lyme disease, six new rickettsioses, three new human ehrlichioses, bartonelloses, and staphylococcal and streptococcal toxic shock syndrome), viral hemorrhagic fevers (e.g., Marburg, Ebola, Lassa, Bolivian, Argentine, and Venezuelan hemorrhagic fevers), human retroviral infections (e.g., HIV1 and 2 and HTLV-I and II), new human herpesviruses (HHV6, HHV7, and HHV8), and the viral agents of hepatitis A, B, C, D, and E. There are the reciprocal threats that a bioterror agent (e.g., smallpox virus) could cause a newly emerging infectious disease (EID) and that an agent of emerging infections (e.g., SARS-coronavirus or Rift Valley fever virus) could be disseminated by terrorists. Vaccines offer a critically important potential countermeasure against the effects of these and future EIDs. An aggressive approach to developing prototype vaccines against each new class of etiologic agent must be driven by public health initiatives because commercial interests will not undertake these projects. The microbe must be completely characterized biologically, molecularly, and genetically. An accurate animal model of the human infectious disease should be developed. The mechanisms of vaccine-induced protective immunity must be elucidated and the antigens that stimulate these mechanisms of protective immune memory identified. Preclinical testing of vaccine candidates should then be completed in the animal models. It would be most effective if subunit vaccine platforms were developed in which new antigen cassettes could be inserted and FDA approval obtained using one or more prototypes. Experience in manufacturing and a track record of effectiveness and safety for vaccines against numerous emerging infectious agents could be achieved for veterinary diseases caused by organisms that also cause emerging human infections (e.g., West Nile virus and ehrlichioses). In the United States, these approaches are driven currently by individual investigator initiative in pursuing the scientific questions through grants from the National Institute of Allergy and Infectious Diseases. Progress occurs, but not at the desired level. An emerging infection with high transmissibility (e.g., R o=10) and a case-fatality rate of 15% would cause global devastating effects at a level on the order of magnitude of a nuclear war. Our efforts to prepare for EIDs fall far short of nuclear attack preparedness during the Cold War.


title: Seroprevalence of three paramyxoviruses; Hendra virus, Tioman virus, Cedar virus and a rhabdovirus, Australian bat lyssavirus, in a range expanding fruit bat, the Grey-headed flying fox (Pteropus poliocephalus)

text: Habitat-mediated global change is driving shifts in species’ distributions which can alter the spatial risks associated with emerging zoonotic pathogens. Many emerging infectious pathogens are transmitted by highly mobile species, including bats, which can act as spill-over hosts for pathogenic viruses. Over three years, we investigated the seroepidemiology of paramyxoviruses and Australian bat lyssavirus in a range-expanding fruit bat, the Grey-headed flying fox (Pteropus poliocephalus), in a new camp in Adelaide, South Australia. Over six, biannual, sampling sessions, we quantified median florescent intensity (MFI) antibody levels for four viruses for a total of 297 individual bats using a multiplex Luminex binding assay. Where appropriate, florescence thresholds were determined using finite mixture modelling to classify bats’ serological status. Overall, apparent seroprevalence of antibodies directed at Hendra, Cedar and Tioman virus antigens was 43.2%, 26.6% and 95.7%, respectively. We used hurdle models to explore correlates of seropositivity and antibody levels when seropositive. Increased body condition was significantly associated with Hendra seropositivity (Odds ratio = 3.67; p = 0.002) and Hendra virus levels were significantly higher in pregnant females (p = 0.002). While most bats were seropositive for Tioman virus, antibody levels for this virus were significantly higher in adults (p < 0.001). Unexpectedly, all sera were negative for Australian bat lyssavirus. Temporal variation in antibody levels suggests that antibodies to Hendra virus and Tioman virus may wax and wane on a seasonal basis. These findings suggest a common exposure to Hendra virus and other paramyxoviruses in this flying fox camp in South Australia.


All that Glitters isn’t Gold: Critical Care in the Time of COVID


title: Probabilistic analysis of the frequencies of amino acid pairs within characterized protein sequences

text: Abstract Here, we describe a unique probabilistic evaluation of the 20, naturally occurring, amino acids and their distributions within the Swiss-Prot and Complete Human Genebank databases. We have developed a computational technique that imparts both directionality and length constraints into searches for unique combinations of amino acids within protein sequences. Using statistical approaches, we have carried out searches of all possible two- and three-residue motifs contained within these databases. This technique is based on the unusually high occurrence of a small number of these motifs when compared to the expected probability of finding a specific residue grouping within a given database. Subsequent filtering of this search to identify such unique combinations has provided several examples that can be used as markers to identify particular proteins within or across databases. We focus on three of these motifs, which were found to be of greatest interest to us. The CC, CM and a combination of the two, CCM motifs all occur either more or less frequently than would be predicted based on standard amino acid distributions within the entire human proteome.


title: Laboratory Findings of COVID-19 Infection are Conflicting in Different Age Groups and Pregnant Women: A Literature Review

text: Abstract Coronavirus disease 2019 (COVID-19), a new type and rapidly spread viral pneumonia, is now producing an outbreak of pandemic proportions. The clinical features and laboratory results of different age groups are different due to the general susceptibility of the disease. The laboratory findings of COVID-19 in pregnant women are also conflicting. Para-clinical investigations including laboratory tests and radiologic findings play an important role in early diagnosis and treatment monitoring of COVID-19. The majority of previous reports on the COVID-19 laboratory results were based on data from the general population and limited information is available based on age difference and pregnancy status. This review aimed to describe the COVID-19 laboratory findings in neonates, children, adults, elderly and pregnant women altogether for the first time. The most attracting and reliable markers of COVID-19 in patients were: normal C-reactive protein (CRP) and very different and conflicting laboratory results regardless of clinical symptoms in neonates, normal or temporary elevated CRP, conflicting WBC count results and procalcitonin elevation in children, lymphopenia and elevated lactate dehydrogenase (LDH) in adult patients, lymphopenia and elevated CRP and LDH in the elderly people and high CRP, leukocytosis and elevated neutrophil ratio in pregnant women.


title: Applying the Readiness for Interprofessional Learning Scale (RIPLS) to medical, veterinary and dual degree Master of Public Health (MPH) students at a private medical institution

text: PURPOSE: With the emergence of zoonoses such as Ebola, many medical educators, have recommended the need for providing Interprofessional Education (IPE) as a pedagogical tool for familiarizing medical (MD) students with the framework of One Health (OH). This is important as students need to understand, the wider impacts of animal and environmental health factors on human health. IPE initiatives which typically incorporate the principles of OH, can provide MD and veterinary (DVM) students with a greater awareness of the role that animal diseases and climate change have on global health. However, negative attitudes to IPE have been reported as a key limitation to IPE implementation. The purpose of this paper is to examine the differences in readiness for interprofessional learning of medical and other allied human health professional students, including veterinarians and students undertaking dual degrees in combination with a Master of Public Health (MPH). Reflecting on Role Theory (RT) and Social Identity Theory (SIT), the paper aims to contribute to the understanding of differences in perceptions that exist between different types of health professionals. METHODS: Students at a medical University enrolled in MD, DVM, DVM MPH and MD MPH programs, were invited to complete the standardized Readiness for Interprofessional Learning Scale (RIPLS), which consists of 19 Likert scale items measuring concepts relating to teamwork, professional identity and roles and responsibilities. A total of 364 students across the four programs took part. Descriptive and inferential statistical analyses were performed to assess differences between the programmes. RESULTS: Results indicate that MD students score lower on the different RIPLS items compared to DVM, MD MPH and DVM MPH students. DVM and DVM MPH students are generally more positive about the need for teamwork, while MD MPH and DVM MPH students have a stronger positive identity about the need for IPE. CONCLUSIONS: The findings drawn from this study suggests that the MD students keep on seeing themselves as a separate group of health professionals in their own right. In order to guarantee an increased level of understanding on issues relating to the human-animal-environmental spectrum, medical curricula might benefit from the incorporation of shared learning and teamwork, as occurs within the MPH, enabling students to appreciate the value of interprofessional collaboration to their future practice. This is especially important during a time at which human-animal-environmental issues are affecting social and economic life worldwide.


title: Evasion of Antiviral Innate Immunity by Theiler's Virus L* Protein through Direct Inhibition of RNase L

text: Theiler's virus is a neurotropic picornavirus responsible for chronic infections of the central nervous system. The establishment of a persistent infection and the subsequent demyelinating disease triggered by the virus depend on the expression of L*, a viral accessory protein encoded by an alternative open reading frame of the virus. We discovered that L* potently inhibits the interferon-inducible OAS/RNase L pathway. The antagonism of RNase L by L* was particularly prominent in macrophages where baseline oligoadenylate synthetase (OAS) and RNase L expression levels are elevated, but was detectable in fibroblasts after IFN pretreatment. L* mutations significantly affected Theiler's virus replication in primary macrophages derived from wild-type but not from RNase L-deficient mice. L* counteracted the OAS/RNase L pathway through direct interaction with the ankyrin domain of RNase L, resulting in the inhibition of this enzyme. Interestingly, RNase L inhibition was species-specific as Theiler's virus L* protein blocked murine RNase L but not human RNase L or RNase L of other mammals or birds. Direct RNase L inhibition by L* and species specificity were confirmed in an in vitro assay performed with purified proteins. These results demonstrate a novel viral mechanism to elude the antiviral OAS/RNase L pathway. By targeting the effector enzyme of this antiviral pathway, L* potently inhibits RNase L, underscoring the importance of this enzyme in innate immunity against Theiler's virus.


title: Acute Stroke Care Is at Risk in the Era of COVID-19: Experience at a Comprehensive Stroke Center in Barcelona

text: BACKGROUND AND PURPOSE: The purpose of the study is to analyze how the coronavirus disease 2019 (COVID-19) pandemic affected acute stroke care in a Comprehensive Stroke Center. METHODS: On February 28, 2020, contingency plans were implemented at Hospital Clinic of Barcelona to contain the COVID-19 pandemic. Among them, the decision to refrain from reallocating the Stroke Team and Stroke Unit to the care of patients with COVID-19. From March 1 to March 31, 2020, we measured the number of emergency calls to the Emergency Medical System in Catalonia (7.5 million inhabitants), and the Stroke Codes dispatched to Hospital Clinic of Barcelona. We recorded all stroke admissions, and the adequacy of acute care measures, including the number of thrombectomies, workflow metrics, angiographic results, and clinical outcomes. Data were compared with March 2019 using parametric or nonparametric methods as appropriate. RESULTS: At Hospital Clinic of Barcelona, 1232 patients with COVID-19 were admitted in March 2020, demanding 60% of the hospital bed capacity. Relative to March 2019, the Emergency Medical System had a 330% mean increment in the number of calls (158 005 versus 679 569), but fewer Stroke Code activations (517 versus 426). Stroke admissions (108 versus 83) and the number of thrombectomies (21 versus 16) declined at Hospital Clinic of Barcelona, particularly after lockdown of the population. Younger age was found in stroke admissions during the pandemic (median [interquartile range] 69 [64–73] versus 75 [73–80] years, P=0.009). In-hospital, there were no differences in workflow metrics, angiographic results, complications, or outcomes at discharge. CONCLUSIONS: The COVID-19 pandemic reduced by a quarter the stroke admissions and thrombectomies performed at a Comprehensive Stroke Center but did not affect the quality of care metrics. During the lockdown, there was an overload of emergency calls but fewer Stroke Code activations, particularly in elderly patients. Hospital contingency plans, patient transport systems, and population-targeted alerts must act concertedly to better protect the chain of stroke care in times of pandemic.


title: Psychiatrist experience of remote consultations by telephone in an outpatient psychiatric department during the COVID-19 pandemic

text: OBJECTIVE: In response to the COVID-19 pandemic, there has been a shift globally from face-to-face consultations to remote consultations. In our department, remote consultations have taken in the form of telephone consultations. In this paper, we set out to study a group of Irish psychiatrists’ experience of these consultations. METHODS: We identified recurrent themes in the existing literature on doctors’ experience of telephone consultations with a view to determining the applicability of these themes to a group of Irish psychiatrists. A questionnaire was developed based on themes in the literature. This was sent to all psychiatrists working in a busy psychiatric service in Dublin. RESULTS: The questionnaire response rate was 72% (n = 26/35). Diagnostic challenges, the effect of phone consultation on the therapeutic alliance, challenges associated with the use of technology and ethical concerns were identified as issues. Flexibility in the working day and convenience were identified as possible benefits to telephone consultations. CONCLUSIONS: The group that participated in this research study identified a number of challenges to carrying out successful phone consultations. This study highlights the need at our clinical site for interventions to address the issues identified by staff. The findings also highlight the requirement for larger studies with stronger methodologies to determine the generalisability of our results.


title: Emergency Preparedness and Public Health Systems Lessons for Developing Countries

text: Abstract Low- and middle-income countries, where emerging diseases often make their debut, are also likely to bear the harshest consequences of a potential influenza pandemic. Yet public health systems in developing countries are underfunded, understaffed, and in many cases struggling to deal with the existing burden of disease. As a result, developed countries are beginning to expand assistance for emergency preparedness to the developing world. Given developing countries' weak infrastructure and many competing public health priorities, it is not clear how to best direct these resources. Evidence from the U.S. and other developed countries suggests that some investments in bioterror and pandemic emergency preparedness, although initially implemented as vertical programs, have the potential to strengthen the general public health infrastructure. This experience may hold some lessons for how global funds for emergency preparedness could be invested in developing countries to support struggling public health systems in responding to current health priorities as well as potential future public health threats.


title: Neurological, Cognitive, and Behavioral Disorders during COVID‐19: The Nitric Oxide Track

text: See the Reply by Alkeridy et al.


title: The agents of non-A, non-B viral hepatitis

text: Abstract Recent studies have provided physicochemical and electron microscopic evidence for the existence of two distinct agents of posttransfusion non-A, non-B (NANB) hepatitis. One of these agents is chloroform-resistant and is not associated with the formation of unique ultrastructural structures in infected liver. The other agent is CHCl3-sensitive, induces the formation of characteristic hepatocyte cytoplasmic tubules, and interferes with concurrent HAV or HBV infection in experimentally inoculated chimpanzees. The tubule-forming agent (TFA) has also been shown to pass through an 80 nm capillary pore membrane filter, suggesting that it is a small enveloped (or lipid-containing) virus. The TFA can also be recovered from low titer (⩽ 105 infectious doses/ml) chronic-phase chimpanzee plasma by use of a multi-step purification procedure that assumes the agent is a small enveloped RNA virus with an approximate buoyant density of 1.24 g/cm3 and a sedimentation coefficient of 200–280 S. The apparent lack of nucleic acid homology between the NANB-TFA and HBV further suggests that the NANB-TFA is either Togavirus-like or belongs to another or as yet undefined class of RNA or DNA virus.


Human Rhinovirus Group C Infection in Children with Lower Respiratory Tract Infection


title: The American College of Nuclear Medicine Guidance on Operating Procedures for a Nuclear Medicine Facility During COVID-19 Pandemic

text: The novel coronavirus 2 pandemic is causing widespread disruption in everyday life necessitating urgent and radical adaptations in operating procedures at Nuclear Medicine facilities. The potential for causing severe illness, COVID-19, calls for strict observance of preventive measures aimed to mitigate the spread of the virus. The threat of COVID-19 is particularly serious as there is no vaccine and no specific antiviral therapy. Further complications are introduced by shortages of personal protective equipment for healthcare workers who have direct contact with patients and effective testing to identify infected patients, raising the need for delaying some testing and therapies. Certain vulnerable segments of the general population have been identified (advanced age and certain comorbidities), which should heighten further their preventive efforts. Therefore, this guidance is intended to be operationalized depending on a facility’s specific needs and local disease prevalence.


title: Severe Acute Respiratory Syndrome: Clinical Outcome and Prognostic Correlates

text: Severe acute respiratory syndrome (SARS) poses a major threat to the health of people worldwide. We performed a retrospective case series analysis to assess clinical outcome and identify pretreatment prognostic correlates of SARS, managed under a standardized treatment protocol. We studied 127 male and 196 female patients with a mean age of 41±14 (range 18–83). All patients, except two, received ribavirin and steroid combination therapy. In 115 (36%) patients, the course of disease was limited. Pneumonitis progressed rapidly in the remaining patients. Sixty-seven (21%) patients required intensive care, and 42 (13%) required ventilator support. Advanced age, high admission neutrophil count, and high initial lactate dehydrogenase level were independent correlates of an adverse clinical outcome. SARS-associated coronavirus caused severe illnesses in most patients, despite early treatment with ribavirin and steroid. This study has identified three independent pretreatment prognostic correlates.


title: Postnatal SARS‐CoV‐2 Infection and Immunological Reaction: A Prospective Family Cohort Study

text: The coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) appears milder in children but little is known about neonates and about the chains of infections after delivery.(1‐3) When in early March 2020 a midwife in our large maternity and perinatal center returned from vacation in Ischgl, Austria, she triggered a COVID‐19 outbreak affecting 36 midwives, nurses and doctors. We reported previously on the successful containment of this outbreak and characterized the clinical symptoms and immunoglobulin development in staff members exposed to SARS‐CoV‐2.(4‐5)


title: Programmable low-cost DNA-based platform for viral RNA detection

text: Viral detection is critical for controlling disease spread and progression. Recent emerging viral threats including Zika, Ebola, and the current COVID-19 outbreak highlight the cost and difficulty in responding rapidly. To address these challenges, we develop a platform for low-cost and rapid detection of viral RNA with DNA nanoswitches designed to mechanically reconfigure in response to specific viruses. Using Zika virus as a model system, we show non-enzymatic detection of viral RNA to the attomole level, with selective and multiplexed detection between related viruses and viral strains. For clinical-level sensitivity in biological fluids, we paired the assay with a sample preparation step using either RNA extraction or isothermal pre-amplification. Our assay can be performed with minimal or no lab infrastructure, and is readily adaptable to detect other viruses. We demonstrate the adaptability of our method by quickly developing and testing DNA nanoswitches for detecting a fragment of SARS-CoV-2 RNA in human saliva. Given this versatility, we expect that further development and field implementation will improve our ability to detect emergent viral threats and ultimately limit their impact.


title: Treatment of disseminated Strongyloides spp. infection in an infant Sumatran orangutan (Pongo abelii)

text: Strongyloides nematodes have been reported in all species of great apes with orangutans ≤5 years old most susceptible to severe clinical disease. This brief communication describes the first published case of antemortem diagnosis and treatment of disseminated strongyloidiasis in a clinically affected 5‐month‐old Sumatran orangutan (Pongo abelii).


title: The Pace of Human-Induced Change in Large Rivers: Stresses, Resilience, and Vulnerability to Extreme Events

text: The world’s great rivers are threatened by a range of anthropogenic stresses—of which climate change is just one—that decrease resilience and increase vulnerability to extreme events. Future governance must recognize both the rate of change associated with these stressors and the potential for extreme events to transgress sustainability thresholds.


title: Does Pathogen Spillover from Commercially Reared Bumble Bees Threaten Wild Pollinators?

text: The conservation of insect pollinators is drawing attention because of reported declines in bee species and the ‘ecosystem services’ they provide. This issue has been brought to a head by recent devastating losses of honey bees throughout North America (so called, ‘Colony Collapse Disorder’); yet, we still have little understanding of the cause(s) of bee declines. Wild bumble bees (Bombus spp.) have also suffered serious declines and circumstantial evidence suggests that pathogen ‘spillover’ from commercially reared bumble bees, which are used extensively to pollinate greenhouse crops, is a possible cause. We constructed a spatially explicit model of pathogen spillover in bumble bees and, using laboratory experiments and the literature, estimated parameter values for the spillover of Crithidia bombi, a destructive pathogen commonly found in commercial Bombus. We also monitored wild bumble bee populations near greenhouses for evidence of pathogen spillover, and compared the fit of our model to patterns of C. bombi infection observed in the field. Our model predicts that, during the first three months of spillover, transmission from commercial hives would infect up to 20% of wild bumble bees within 2 km of the greenhouse. However, a travelling wave of disease is predicted to form suddenly, infecting up to 35–100% of wild Bombus, and spread away from the greenhouse at a rate of 2 km/wk. In the field, although we did not observe a large epizootic wave of infection, the prevalences of C. bombi near greenhouses were consistent with our model. Indeed, we found that spillover has allowed C. bombi to invade several wild bumble bee species near greenhouses. Given the available evidence, it is likely that pathogen spillover from commercial bees is contributing to the ongoing decline of wild Bombus in North America. Improved management of domestic bees, for example by reducing their parasite loads and their overlap with wild congeners, could diminish or even eliminate pathogen spillover.


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title: Human Metapneumovirus Detection in Patients with Severe Acute Respiratory Syndrome

text: We used a combination approach of conventional virus isolation and molecular techniques to detect human metapneumovirus (HMPV) in patients with severe acute respiratory syndrome (SARS). Of the 48 study patients, 25 (52.1%) were infected with HMPV; 6 of these 25 patients were also infected with coronavirus, and another 5 patients (10.4%) were infected with coronavirus alone. Using this combination approach, we found that human laryngeal carcinoma (HEp-2) cells were superior to rhesus monkey kidney (LLC-MK2) cells commonly used in previous studies for isolation of HMPV. These widely available HEp-2 cells should be included in conjunction with a molecular method for cell culture followup to detect HMPV, particularly in patients with SARS.


title: Letter: Covid‐19, and vitamin D

text: LINKED CONTENT This article is linked to Tian et al and Tian and Rong papers. To view these articles, visit https://doi.org/10.1111/apt.15731 and https://doi.org/10.1111/apt.15764.


title: Key elements of the human bocavirus type 1 (HBoV1) promoter and its trans-activation by NS1 protein

text: BACKGROUND: Human bocavirus (HBoV), a parvovirus, is suspected to be an etiologic agent of respiratory disease and gastrointestinal disease in humans. All mRNAs of HBoV1 are transcribed from a single promoter. METHODS: In this study, we constructed EGFP and luciferase reporter gene vectors under the control of the HBoV1 full promoter (nt 1–252) and its mutated variants, respectively. Fluorescence microscopy was used to observe expression activities of the EGFP. Dual-luciferase reporter vectors were employed in order to evaluate critical promoter elements and the effect of NS1 protein on promoter activity. RESULTS: The HBoV1 promoter activity was about 2.2-fold and 1.9-fold higher than that of the CMV promoter in 293 T and HeLa cells, respectively. The putative transcription factor binding region of the promoter was identified to be located between nt 96 and nt 145. Mutations introduced in the CAAT box of the HBoV1 promoter reduced promoter activity by 34%, whereas nucleotide substitutions in the TATA box had no effect on promoter activity. The HBoV1 promoter activities in 293 T and HeLa cells, in the presence of NS1 protein, were 2- to 2.5-fold higher than those in the absence of NS1 protein. CONCLUSION: The HBoV1 promoter was highly active in 293 T and HeLa cell lines, and the sequence from nt 96 to nt 145 was critical for the activity of HBoV1 promoter. The CAAT box, in contrast to the TATA-box, was important for optimum promoter activity. In addition, the transcriptional activity of this promoter could be trans-activated by the viral nonstructural protein NS1 in these cells.


The corona crisis unmasks prevailing social ideologies


title: Detection of human coronavirus strain HKU1 in a 2 years old girl with asthma exacerbation caused by acute pharyngitis

text: Respiratory viral infections can trigger asthma attack which may lead to sever morbidity. In this report, using molecular methods, we show the chronological association between human coronavirus - HKU1 infection and asthma exacerbation in a two years and seven months old asthmatic girl who was not under treatment and was otherwise healthy.


title: SARS‐CoV‐2 infection‐induced immune responses: friends or foes?

text: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is an emerging coronavirus that belongs to the β genus, causing the outbreak of coronavirus disease 19 (COVID‐19). SARS‐CoV‐2 infection can stimulate a pronounced immune response in the host, which embodies in the decrease of lymphocytes and aberrant increase of cytokines in COVID‐19 patients. SARS‐CoV‐2 RNA and proteins interact with various pattern recognition receptors that switch on antiviral immune responses to regulate viral replication and spreading within the host in vivo. However, overactive and impaired immune responses also cause immune damage and subsequent tissue inflammation. This article focuses on the dual roles of immune system during SARS‐CoV‐2 infection, providing a theoretical basic for identifying therapeutic targets in a situation with an unfavorable immune reaction.


title: Protective Efficacy of Different Live Attenuated Infectious Bronchitis Virus Vaccination Regimes Against Challenge With IBV Variant-2 Circulating in the Middle East

text: Six vaccination regimes using classical (Mass-type) and variant (IB-VAR2 and IB-793B) live vaccines were evaluated against Middle Eastern variant-2 infectious bronchitis virus challenge. Six groups of SPF chicks (30 birds/group) were vaccinated using prime-boost regimes at day-1 and day-14 using; IB-M41:IB-VAR2, IB-VAR2:IB-VAR2, IB-VAR2:IB-M41, IB-Ma5:IB-793B, IB-793B:IB-793B, and IB-793B:IB-Ma5, respectively. Ciliostasis and lesion scores were evaluated at day-5 after each vaccination. Birds were challenged intranasally at 14-day post 2nd vaccination using 10(5)EID(50)/0.1 ml/bird of wild-type IBV (Eg/1212B/2012). At 3, 5, and 7-day post challenge (DPC) virus shedding was monitored by real-time RT-PCR. Five chicks/group were euthanized at 7DPC for ciliostasis and lesion scoring and histopathology was conducted on 3 chicks/group. Seroconversion was evaluated at 14 DPC. All groups primed with the 793B vaccine showed relatively higher ciliostasis scores compared to other groups. The IB-VAR2 vaccinated groups showed the highest protection rates (80–100%) and high protection score (67.6–73.2%) compared to the 793B vaccine groups (50–60%). The virus shedding was significantly reduced at 3 and 5DPC in groups received the IBV-VAR2 (prime or booster) compared to those received the 793B vaccine. In conclusion, the homologous IBV-VAR2 vaccine showed superior results compared to 793B or Mass-type vaccines confirming the importance of IBV vaccine seed homology to the circulating IBV strains.


title: Epidemiology of necrotizing enterocolitis

text: Necrotizing enterocolitis (NEC) is a worldwide problem that has emerged in the past 25 years as the most common gastrointestinal emergency in neonatal intensive care units (NICU). In the United States the incidence ranges from 1 to 7.7% of NICU admissions. Ninety percent of the patients are premature infants. Mucosal injury, bacterial colonization and formula feeding are the three major pathogenetic factors that have been documented in most infants who have developed NEC. However, NEC may develop only if a threshold of injury, imposed by the coincidence of at least two of three events (intestinal ischemia, pathogenic bacteria, and excess of protein substrate) is exceeded. Immunological immaturity of the gut in premature babies may represent the crucial risk factor.


title: Molecular Basis of the Differentiation and Function of Virus Specific Follicular Helper CD4(+) T Cells

text: During viral infection, virus-specific follicular helper T cells provide important help to cognate B cells for their survival, consecutive proliferation and mutation and eventual differentiation into memory B cells and antibody-secreting plasma cells. Similar to Tfh cells generated in other conditions, the differentiation of virus-specific Tfh cells can also be characterized as a process involved multiple factors and stages, however, which also exhibits distinct features. Here, we mainly focus on the current understanding of Tfh fate commitment, functional maturation, lineage maintenance and memory transition and formation in the context of viral infection.


title: Key Vitamin D Target Genes with Functions in the Immune System

text: The biologically active form of vitamin D(3), 1α,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), modulates innate and adaptive immunity via genes regulated by the transcription factor vitamin D receptor (VDR). In order to identify the key vitamin D target genes involved in these processes, transcriptome-wide datasets were compared, which were obtained from a human monocytic cell line (THP-1) and peripheral blood mononuclear cells (PBMCs) treated in vitro by 1,25(OH)(2)D(3), filtered using different approaches, as well as from PBMCs of individuals supplemented with a vitamin D(3) bolus. The led to the genes ACVRL1, CAMP, CD14, CD93, CEBPB, FN1, MAPK13, NINJ1, LILRB4, LRRC25, SEMA6B, SRGN, THBD, THEMIS2 and TREM1. Public epigenome- and transcriptome-wide data from THP-1 cells were used to characterize these genes based on the level of their VDR-driven enhancers as well as the level of the dynamics of their mRNA production. Both types of datasets allowed the categorization of the vitamin D target genes into three groups according to their role in (i) acute response to infection, (ii) infection in general and (iii) autoimmunity. In conclusion, 15 genes were identified as major mediators of the action of vitamin D in innate and adaptive immunity and their individual functions are explained based on different gene regulatory scenarios.


Expanding the Paradigms of Plant Pathogen Life History and Evolution of Parasitic Fitness beyond Agricultural Boundaries


title: Incidence of Adverse Drug Reactions in COVID‐19 Patients in China: An Active Monitoring Study by Hospital Pharmacovigilance System

text: To evaluate the incidence, type, and risk factors associated with adverse drug reactions (ADRs) among patients with coronavirus disease 2019 (COVID‐19) by Hospital Pharmacovigilance System (CHPS). A retrospective analysis was performed on 217 patients with COVID‐19 admitted to the First Hospital of Changsha in China, from January 17, 2020, to February 29, 2020. The active monitoring model in CHPS was used to detect ADR signals of the hospital information system. The risk factors for the ADRs were classified using the World Health Organization‐Uppsala Monitoring Centre (WHO‐UMC) system. Univariate and multivariate logistic regressions were carried out to analyze the risk factors of ADRs. Our results showed that the prevalence of ADRs was 37.8% in the patients, which was predominated by drug‐induced gastrointestinal disorders and liver system disorders (23.0% vs. 13.8%). The ADR could be explained by the use of lopinavir/ ritonavir and umifenovir by 63.8% and 18.1%, respectively. There were 96.8% of ADRs that occurred within 14 days of hospitalization. Multivariable analysis showed that length of stay (odds ratio (OR): 2.02; 95% confidence interval (CI) 1.03–3.96; P = 0.04), number of drugs used in the hospital (OR: 3.17; 95% CI 1.60–6.27; P = 0.001) and underlying basic diseases (OR: 2.07; 95% CI 1.02–4.23; P = 0.04) were independent risk factor for ADRs in the patients. Together, the incidence of ADRs was significantly high during the treatment period. Moreover, the active monitoring of the CHPS system reflected ADRs during COVID‐19 treatment in the real world, which provided reference for safe medication in the clinic.


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title: The pathogenesis of an enteric infection in pigs, experimentally induced by the coronavirus-like agent, CV 777

text: Abstract Sixteen 2–3-days-old caesarean-derived, colostrum-deprived piglets were each dosed oro-nasally with 2 ml of a bacteria-free filtrate containing 104 pig-infectious-doses of CV 777. The piglets were killed at intervals of 12 to 120 h after infection. The coronvirus-like agent caused a local infection of the intestinal tract which resulted in villous atrophy, malabsorption and diarrhea. The pathogenesis of this infection was similar to that of transmissible gastroenteritis (TGE), a known coronaviral infection of pigs. However, where were some differences. By immunofluorescent staining, CV 777 antigens were not only detected in the epithelial cells covering the small intestinal villi, but also in the cells of the colonic surface epithelium. Occasional fluorescence was also seen in the small intestinal crypt epithelium, but the regenerative capacity of the crypts was not affected. The progress of intestinal epithelial cell infection by CV 777 was much slower than that in TGE, resulting in a longer incubation period and in less drastic epithelial cell destruction. The infection of regenerating cells occurred to a much higher degree during the late stage of a CV 777 infection than has been observed in TGE.


title: Chapter 642 Coagulation Factor Xa

text: The third edition of the Handbook of Proteolytic Enzymes aims to be a comprehensive reference work for the enzymes that cleave proteins and peptides, and contains over 800 chapters. Each chapter is organized into sections describing the name and history, activity and specificity, structural chemistry, preparation, biological aspects, and distinguishing features for a specific peptidase. The subject of Chapter 642 is Coagulation Factor Xa. Keywords Coagulation factor, prothrombin, thrombin, proconvertin, Stuart’s factor, Prower’s factor.


title: A Review and Update on Waterborne Viral Diseases Associated with Swimming Pools

text: Infectious agents, including bacteria, viruses, protozoa, and molds, may threaten the health of swimming pool bathers. Viruses are a major cause of recreationally-associated waterborne diseases linked to pools, lakes, ponds, thermal pools/spas, rivers, and hot springs. They can make their way into waters through the accidental release of fecal matter, body fluids (saliva, mucus), or skin flakes by symptomatic or asymptomatic carriers. We present an updated overview of epidemiological data on viral outbreaks, a project motivated, among other things, by the availability of improved viral detection methodologies. Special attention is paid to outbreak investigations (source of the outbreak, pathways of transmission, chlorination/disinfection). Epidemiological studies on incidents of viral contamination of swimming pools under non-epidemic conditions are also reviewed.


title: Papel de las infecciones víricas en pacientes inmunodeprimidos

text: Being a solid organ and hematopoietic stem cell transplant recipient as well as receiving chemotherapy for a malignant hematological disease clearly predispose the subject to a variety of viral infections, both common and opportunistic diseases. The patient may have acquired these infections from the community as well as from the donor organ (donor-derived infections) and/or from reactivation of an endogenous latent virus. Herpes viruses and especially the cytomegalovirus and Epstein-Barr virus are among the most common of the opportunistic viral pathogens affecting these patients, in addition to respiratory viruses. Treatment consists in antiviral drug therapies combined with the reduction in the degree of the induced immunosuppression. A review of the literature has been performed in order to update the epidemiology, pathogenesis, clinical manifestations and therapeutic approach of the viral infections in these immunocompromised patients.


title: Prevalence of major depressive disorder and socio-demographic correlates: Results of a representative household epidemiological survey in Beijing, China

text: Abstract Background Major depressive disorder (MDD) is the most prevalent mental disorder in the general population and has been associated with socioeconomic factors. Beijing has undergone significant socioeconomic changes in last decade, however no large-scale community epidemiological surveys of MDD have been conducted in Beijing since 2003. Aims To determine the prevalence of MDD and its socio-demographic correlates in a representative household sample of the general population in Beijing, China. Method Data were collected from the 2010 representative household epidemiological survey of mental disorders in Beijing. The multistage cluster random sampling method was used to select qualified subjects in 18 districts and counties, and then face-to-face interviews were administered using the Chinese version of Structured Clinical Interview for DSM-IV-TR Axis I Disorders-Patient Edition (SCID-I/P) during November 1, 2010 to December 31, 2010. Results 19,874 registered permanent residents were randomly identified and 16,032 (response rate=80.7%) completed face-to-face interviews. The time-point and life-time prevalence rates of MDD were estimated to be 1.10% (95% CI: 0.94–1.26%) and 3.56% (95% CI: 3.27–3.85%) respectively. Significant differences were found in sex, age, location of residence, marital status, education, employment status, personal/family monthly income, perception of family environment and relationship with others, when comparing residents with MDD to those without MDD. Those who were female, aged 45 or above, reported low family income, or reported an “average” or “poor” family environment were associated with a higher risk of MDD. Conclusions The prevalence of MDD reported in this survey is relatively lower than that in other western countries. Female sex, age older than 45, low family income, and poor family environment appear to be independent risk factors for MDD.


Emergency Preparedness and Mass Casualty Considerations for Anesthesiologists


docid: rxokovog

title: Iraq: time to signal a new era for health in foreign policy


title: Health and health-care systems in southeast Asia: diversity and transitions

text: Southeast Asia is a region of enormous social, economic, and political diversity, both across and within countries, shaped by its history, geography, and position as a major crossroad of trade and the movement of goods and services. These factors have not only contributed to the disparate health status of the region's diverse populations, but also to the diverse nature of its health systems, which are at varying stages of evolution. Rapid but inequitable socioeconomic development, coupled with differing rates of demographic and epidemiological transitions, have accentuated health disparities and posed great public health challenges for national health systems, particularly the control of emerging infectious diseases and the rise of non-communicable diseases within ageing populations. While novel forms of health care are evolving in the region, such as corporatised public health-care systems (government owned, but operating according to corporate principles and with private-sector participation) and financing mechanisms to achieve universal coverage, there are key lessons for health reforms and decentralisation. New challenges have emerged with rising trade in health services, migration of the health workforce, and medical tourism. Juxtaposed between the emerging giant economies of China and India, countries of the region are attempting to forge a common regional identity, despite their diversity, to seek mutually acceptable and effective solutions to key regional health challenges. In this first paper in the Lancet Series on health in southeast Asia, we present an overview of key demographic and epidemiological changes in the region, explore challenges facing health systems, and draw attention to the potential for regional collaboration in health.


title: Orthopedics and COVID-19: Scientific Publications Rush

text: BACKGROUND: The purpose of this literature review is to analyze all the articles related to COVID-19 and orthopedics and to shed light on the scientific evidence that has actually been found. METHODS: A systematic review of the existing literature was performed to identify all studies dealing with COVID-19 and orthopedics. The guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) were followed for the identification of the articles. On April 19 2020, a search was performed using MEDLINE and PubMed Central. For the research, the following terms were used: “COVID-19” OR “SARS-CoV-2” OR “Coronavirus” AND “orthopaedic” OR “orthopedic” OR “traumatology”. RESULTS: A total of 23 studies were included in the review, of which 19 (82.6%) were editorials, letters to editors, orthopedic forums or expert opinions, 3 (13.0%) studies were level IV of evidence and 1 (4.4%) was a literature review. Articles have been divided into the follow categories: guidelines, traumatology, pediatric, spine surgery, telemedicine, sports medicine, bioethical, educational, rehabilitation, survey and hand surgery. CONCLUSIONS: Although scientific production is very active on the topic of COVID-19 and orthopedics, the scientific evidence is practically nil, mainly dealing with editorials, letters to editors or expert opinions. Therefore, future studies should focus on clinical outcomes and treatments in COVID-19-positive orthopedic patients and prevention strategies. Additionally, international guidelines and consensus statements must be developed to standardize procedures as much as possible in this pandemic scenario.


title: Gastrointestinal Manifestations of AIDS

text: Although gastrointestinal complications have decreased dramatically in patients with acquired immunodeficiency syndrome (AIDS) who received highly active antiretroviral therapy, these disorders still occur in those who do not seek healthcare, those with resistant virus, and those in developing countries where these drugs are not available. Opportunistic infections are the most frequent causes of gastrointestinal disease in patients with AIDS. A practical approach based on the character of the complaints and location of symptoms will help direct the most appropriate evaluation. In most patients, a diagnosis should be sought because effective antimicrobial therapy is available for most infections in these patients. When possible, improvement in immune function forms an integral part of the treatment regimen.


title: Conservation as vaccination: Integrated approaches to public health and environmental protection could prevent future disease outbreaks

text: The main lesson from the 2015 Ebola outbreak is that we need to increase global preparedness to better deal with zoonotic disease outbreaks. Yet, it might be a more efficient strategy to prevent such zoonotic spillover events in the first place through conservation measures to protect biodiversity and wildlife. [Image: see text]


RILI model and the Covid-19 pneumonia: the radiation oncologist point of view


title: Visibility and transmission: complexities around promoting hand hygiene in young children – a qualitative study

text: BACKGROUND: Effective hand hygiene practice can reduce transmission of diseases such as respiratory tract infections (RTIs) and gastrointestinal infections, especially in young children. While hand hygiene has been widely promoted within Australia, primary care providers’ (PCPs) and parents’ understanding of hand hygiene importance, and their views on hand hygiene in reducing transmission of diseases in the community are unclear. Therefore, the aim of this study was to explore the views of PCPs and parents of young children on their knowledge and practice of hand hygiene in disease transmission. METHODS: Using a cross-sectional qualitative research design, we conducted 30 in-depth interviews with PCPs and five focus groups with parents (n = 50) between June 2014 and July 2015 in Melbourne, Australia. Data were thematically analysed. RESULTS: Participants agreed that hand hygiene practice was important in reducing disease transmissions. However, barriers such as variations of hand hygiene habits, relating visibility to transmission; concerns around young children being obsessed with washing hands; children already being ‘too clean’ and the need to build their immunity through exposure to dirt; and scepticism that hand hygiene practice was achievable in young children, all hindered participants’ motivation to develop good hand hygiene behaviour in young children. CONCLUSION: Despite the established benefits of hand hygiene, sustained efforts are needed to ensure its uptake in routine care. To overcome the barriers identified in this study a multifaceted intervention is needed that includes teaching young children good hand hygiene habits, PCPs prompting parents and young children to practice hand hygiene when coming for an RTI consultation, reassuring parents that effective hand hygiene practice will not lead to abnormal psychological behaviour in their children, and community health promotion education campaigns.


title: Administration of Δ9‐Tetrahydrocannabinol (THC) Post‐Staphylococcal Enterotoxin B Exposure Protects Mice From Acute Respiratory Distress Syndrome and Toxicity

text: Acute Respiratory Distress Syndrome (ARDS) is a life-threatening complication that can ensue following Staphylococcus aureus infection. The enterotoxin produced by these bacteria (SEB) acts as a superantigen thereby activating a large proportion of T cells leading to cytokine storm and severe lung injury. Δ9Tetrahydrocannabinol (THC), a psychoactive ingredient found in Cannabis sativa, has been shown to act as a potent anti-inflammatory agent. In the current study, we investigated the effect of THC treatment on SEB-induced ARDS in mice. While exposure to SEB resulted in acute mortality, treatment with THC led to 100% survival of mice. THC treatment significantly suppressed the inflammatory cytokines, IFN-γ and TNF-α. Additionally, THC elevated the induction of regulatory T cells (Tregs) and their associated cytokines, IL-10 and TGF-β. Moreover, THC caused induction of Myeloid-Derived Suppressor Cells (MDSCs). THC acted through CB2 receptor as pharmacological inhibitor of CB2 receptors blocked the anti-inflammatory effects. THC-treated mice showed significant alterations in the expression of miRNA (miRs) in the lung-infiltrated mononuclear cells (MNCs). Specifically, THC caused downregulation of let7a-5p which targeted SOCS1 and downregulation of miR-34-5p which caused increased expression of FoxP3, NOS1, and CSF1R. Together, these data suggested that THC-mediated alterations in miR expression in the lungs may play a critical role in the induction of immunosuppressive Tregs and MDSCs as well as suppression of cytokine storm leading to attenuation of SEB-mediated lung injury.


title: Modelling in infectious diseases: between haphazard and hazard

text: Modelling of infectious diseases is difficult, if not impossible. No epidemic has ever been truly predicted, rather than being merely noticed when it was already ongoing. Modelling the future course of an epidemic is similarly tenuous, as exemplified by ominous predictions during the last influenza pandemic leading to exaggerated national responses. The continuous evolution of microorganisms, the introduction of new pathogens into the human population and the interactions of a specific pathogen with the environment, vectors, intermediate hosts, reservoir animals and other microorganisms are far too complex to be predictable. Our environment is changing at an unprecedented rate, and human-related factors, which are essential components of any epidemic prediction model, are difficult to foresee in our increasingly dynamic societies. Any epidemiological model is, by definition, an abstraction of the real world, and fundamental assumptions and simplifications are therefore required. Indicator-based surveillance methods and, more recently, Internet biosurveillance systems can detect and monitor outbreaks of infections more rapidly and accurately than ever before. As the interactions between microorganisms, humans and the environment are too numerous and unexpected to be accurately represented in a mathematical model, we argue that prediction and model-based management of epidemics in their early phase are quite unlikely to become the norm.


title: Repositionnement de la chlorpromazine dans le traitement du COVID-19: étude reCoVery

text: Abstract Objectives: The ongoing COVID-19 pandemic has caused approximately 2,350,000 infections worldwide and killed more than 160,000 individuals. In Sainte Anne Hospital (GHU PARIS Psychiatrie & Neuroscience, Paris, France) we have observed a lower incidence of symptomatic forms of COVID-19 among patients than among our clinical staff. This observation led us to hypothesize that psychotropic drugs could have a prophylactic action against SARS-CoV-2 and protect patients from the symptomatic and virulent forms of this infection, since several of these psychotropic drugs have documented antiviral properties. Chlorpromazine (CPZ), a phenothiazine derivative, is also known for its antiviral activity via the inhibition of clathrin-mediated endocytosis. Recent in vitro studies have reported that CPZ exhibits anti-MERS-CoV and anti-SARS-CoV-1 activity. Methods: In this context, the ReCoVery study aims to repurpose CPZ, a molecule with an excellent tolerance profile and a very high biodistribution in the saliva, lungs and brain. We hypothesize that CPZ could reduce the unfavorable course of COVID-19 infection among patients requiring respiratory support without the need for ICU care, and that it could also reduce the contagiousness of SARS-CoV-2. For this purpose, we plan a pilot, multicenter, randomized, single blind, controlled, phase III therapeutic trial (standard treatment vs. CPZ + standard treatment). Conclusion: This repurposing of CPZ for its anti-SARS-CoV-2 activity could offer an alternative, rapid strategy to alleviate infection severity. This repurposing strategy also avoids numerous developmental and experimental steps, and could save precious time to rapidly establish an anti-COVID-19 therapy with well-known, limited and easily managed side effects. Résumé Objectifs: La pandémie mondiale actuelle de COVID-19 a touché environ 2 350 000 personnes et fait plus de 160 000 morts. Nous avons observé dans le GHU PARIS Psychiatrie & Neurosciences (site Sainte-Anne, Paris, France) une incidence moins importante de formes symptomatiques de COVID-19 chez les patients que dans notre personnel soignant. Notre hypothèse est que les traitements psychotropes pourraient avoir une action prophylactique sur le SARS-CoV-2. Cette hypothèse est cohérente avec les propriétés antivirales connues de plusieurs psychotropes au premier rang desquels la chlorpromazine (CPZ). En plus de ses effets antipsychotiques classiques, plusieurs études in vitro ont également démontré une activité antivirale de cette phénothiazine via l'inhibition de l'endocytose dépendante des clathrines. Récemment, des études ont révélé un effet anti-MERS-CoV et anti-SARS-CoV-1 de la CPZ. Méthodes: Dans ce contexte, l’étude reCoVery, basée sur le repositionnement de la CPZ -molécule avec un excellent profil de tolérance et une biodistribution très élevée dans la salive, les poumons et le cerveau - vise à tester l’hypothèse que la CPZ pourrait diminuer l’évolution défavorable de l’infection COVID-19 chez des patients oxygénorequérants sans nécessité de soins en réanimation mais aussi réduire la contagiosité du SARS-CoV-2. Nous allons réaliser pour cela un essai thérapeutique pilote de phase III multicentrique, randomisé, contrôlé (traitement standard vs. CPZ + traitement standard) et en simple insu. Conclusion: Le repositionnement de la CPZ comme antiviral anti-SARS-CoV-2 offre une stratégie alternative et rapide pour atténuer la propagation du virus ainsi que la gravité et la létalité du COVID-19.


title: A dominant antigenic epitope on SARS-CoV spike protein identified by an avian single-chain variable fragment (scFv)-expressing phage

text: Abstract Severe acute respiratory syndrome (SARS) is a newly emergent human disease, which requires rapid diagnosis and effective therapy. Among antibody sources, immunoglobulin Y (IgY) is the major antibody found in chicken eggs and can be used as an alternative to mammalian antibodies normally used in research and immunotherapy. In this study, phage-expressing chicken monoclonal scFv antibody was chosen and characterized with phage display antibody technology. Truncated fragments of SARS-CoV spike protein were cloned in pET-21 vector and expressed in BL-21 Escherichia coli (E. coli) cells. After purification, the purity of these recombinant spike proteins was examined on SDS–PAGE and their identity verified with Western blot analysis using anti-his antibodies and sera from convalescent stage SARS-CoV-infected patients. Using these bacteria-derived proteins to immunize chickens, it was found that polyclonal IgY antibodies in the egg yolk and sera were highly reactive to the immunogens, as shown by Western blot and immunocytochemical staining analysis. A phage displaying scFv library was also established from spleen B cells of immunized chicken with 5×107 clones. After four panning cycles, the eluted phage titer showed a 10-fold increase. In sequence analysis with chicken germline gene, five phage clones reacted, with large dissimilarities of between 31 and 62%, in the complementarity-determining regions, one dominant phage 4S1 had strong binding to fragment Se-e, located between amino acid residues 456–650 of the spike protein and this particular phage had significantly strong binding to SARS-CoV-infected Vero E6 cells. Based on the results, we conclude that generating specific scFv-expressing phage binders with the phage display system can be successfully achieved and that this knowledge can be applied in clinical or academic research.


Navigating the storm of COVID‐19 for patients with suspected bowel cancer


Flawed disinfectant recommendations during a pandemic


title: Inhibition of Helicobacter pylori sialic acid-specific haemagglutination by human gastrointestinal mucins and milk glycoproteins

text: Abstract Helicobacter pylori, a human gastric pathogen causing chronic gastritis and duodenal ulcer disease, has been found in large amounts in gastric mucous gel layer. Mucin preparations, separated from human gastric juices and isolated from different colon regions, were examined for their ability to inhibit haemagglutination of H. pylori with the emphasis on evaluating the role of sialic acid-dependent haemagglutinins of the bacteria in colonisation of the stomach. The mucins showed high inhibitory activity for H. pylori, which was significantly decreased after the removal of sialic acids from the mucins. The inhibitory potencies using high molecular mass mucin-like components from bovine milk were comparable with those obtained for gastric mucins, suggesting their possible role in the prevention of H. pylori infection.


title: Managing Toronto Citywide Health Crises Through 2-1-1 Services

text: Abstract Information and referral systems such as 2-1-1 can be key partners in responding to community-wide health crises and other emergency and disaster events. This paper describes the experience of Toronto 2-1-1 dealing with the 2003 severe acute respiratory syndrome (SARS) epidemic and later that year the Great Northeastern Blackout. It shares five lessons learned from these experiences and describes how they have shaped the current approach to emergency and disaster response at Toronto 2-1-1 (now 2-1-1 Central Region Ontario).


Coronavirus: doctor who faced backlash from police after warning of outbreak dies.


title: Human Respiratory Viruses

text: Viruses are the leading causes of acute lower respiratory-tract infection in infancy. Respiratory syncytial virus (RSV) is the most common pathogen, with hMPV, PIV-3, influenza viruses, and rhinoviruses accounting for the majority of the remainder of acute viral respiratory infections. Humans generally do not develop lifelong immunity to reinfection with these viruses; rather, specific immunity protects against severe and lower respiratory-tract disease.


title: Seroprevalence of Antibody to Severe Acute Respiratory Syndrome (SARS)–Associated Coronavirus among Health Care Workers in SARS and Non-SARS Medical Wards

text: The seroprevalence of antibody to severe acute respiratory syndrome (SARS)–associated coronavirus (SARS-CoV) in cohorts of health care workers (HCWs) with subclinical infection in SARS and non-SARS medical wards was 2.3% (3 of 131 HCWs) and 0% (0 of 192 HCWs), respectively. Rates for clinical SARS-CoV infection among 742 HCWs on these wards were highest among nurses (11.6%) and health care assistants (11.8%), indicating that these occupations are associated with the highest risks for exposure.


Low-Incidence, High-Consequence Pathogens


title: Lesion size changes in osteonecrosis of the femoral head: a long-term prospective study using MRI

text: Osteonecrosis of the femoral head (ONFH) is one of the intractable diseases. It is controversial whether the lesion size assessed by magnetic resonance imaging (MRI) can change over time without any operative treatment. In this study, we used MRI to observe the lesion size changes of ONFH induced by corticosteroid administration in severe acute respiratory syndrome (SARS) patients. The study included 51 SARS patients (84 hips) with early-stage ONFH who did not receive any operative treatment and were diagnosed by MRI. All of the patients underwent MRI follow-ups. Each patient was evaluated on the basis of the lesion volume on MRI at every follow-up for further comparisons. At the first MRI scan, the mean lesion volume was 10.12 ± 8.05 cm(3) (range: 0.39–41.62 cm(3)). At the mid-term follow-up (2.5 years), the mean lesion volume was 7.82 ± 7.59 cm(3) (range: 0.11–39.65 cm(3)). At the final follow-up (five years), complete regression of the lesion was observed in six hips, and the mean lesion volume was 5.67 ± 6.58 cm(3) (range: 0.00–31.47 cm(3)). Overall, the lesion volume was reduced by >15% in 80 hips, and only four hips with relatively larger lesion volumes showed no apparent reductions. The reduction in lesion size of ONFH observed on MRI is a slow, discontinuous and time-dependent process.


title: Rapid Transient Production of a Monoclonal Antibody Neutralizing the Porcine Epidemic Diarrhea Virus (PEDV) in Nicotiana benthamiana and Lactuca sativa

text: Porcine epidemic diarrhea virus (PEDV) causes acute diarrhea, vomiting, dehydration, weight loss, and high mortality rate in neonatal piglets. Porcine epidemic diarrhea (PED) has been reported in Europe, America, and Asia including Thailand. The disease causes substantial losses to the swine industry in many countries. Presently, there is no effective PEDV vaccine available. In this study, we developed a plant-produced monoclonal antibody (mAb) 2C10 as a prophylactic candidate to prevent the PEDV infection. Recently, plant expression systems have gained interest as an alternative for the production of antibodies because of many advantages, such as low production cost, lack of human and animal pathogen, large scalability, etc. The 2C10 mAb was transiently expressed in Nicotiana benthamiana and lettuce using geminiviral vector. After purification by protein A affinity chromatography, the antibody was tested for the binding and neutralizing activity against PEDV. Our result showed that the plant produced 2C10 mAb can bind to the virus and also inhibit PEDV infection in vitro . These results show excellent potential for a plant-expressed 2C10 as a PEDV prophylaxis and a diagnostic for PEDV infection.


title: Systems pharmacology uncovers Janus functions of botanical drugs: activation of host defense system and inhibition of influenza virus replication

text: Given the imminent threat of influenza pandemics and continuing emergence of new drug-resistant influenza virus strains, novel strategies for preventing and treating influenza disease are urgently needed. Herbal medicine, used for thousands of years in combinational therapies (Herb Formula), plays a significant role in stimulating the host immune system in vivo, and meanwhile, in fighting against the pandemic by directly inhibiting influenza virus in vitro. Such potential Janus functions may spark interest in therapeutic manipulation of virus diseases. Unfortunately, the molecular mechanism of the Janus functions of the medicinal herbs in the treatment of influenza remains unclear. In this work, to illustrate the therapeutic concept of Janus functions in the treatment of influenza, we have introduced a novel systems pharmacology model that integrates pharmacokinetic screening, targeting and network analysis of two representative herbs Lonicera japonica and Fructus Forsythiae that are efficient in the treatment of influenza, inflammation and other diseases. 50 Chemicals with favorable pharmacokinetic profiles have been identified for the two herbs, and the ligand–target network was constructed by complementing the literature-based experimental data deposited in DrugBank. The annotation of these chemicals was assigned using a novel drug targeting approach, and mapped to target–disease and drug–target–pathway networks. The overall data suggest that the medicinal herbs function by indirectly suppressing the virus proliferation via regulating the immune systems in hosts, and also, by directly inhibiting virus proliferation through targeting viral proteins essential for the viral life cycle. For the first time, we have demonstrated the mechanism of medicinal herbs in prevention and treatment of virus diseases via the Janus functions on a systematic level.


title: Clinical features of 2019 novel coronavirus infection in Beijing.

text: Background A new coronavirus pneumonia caused by 2019 new coronavirus (2019-nCoV) is spreading in China. Here we summarized the patients we accepted in the fever outpatient department. Methods Patients with epidemiologic history, respiratory symptoms or fever were required to go to the fever clinic for screening. Patients were finally laboratory-confirmed 2019-nCoV infection by real-time reverse transcription-polymerase chain reaction (RT-PCR) using nasal and pharyngeal swabs. Epidemiologic features, clinical presentation, laboratory findings and image features were collected and analyzed. Results Totally, 16 patients were diagnosed as 2019-nCoV infection. The median age of the patients was 39.00 (35.25-55.75) years old, and the ratio of men and women was 9:7. Fifteen (93.75%) patients had clear epidemiologic history. The most common symptoms of the patients were fever (87.50%) and cough (n=8, 50.00%). The mean white blood cell count in the patients was (4.97±1.71) ×109/L, and it was lower than 4.00×109/L in 4 (25.00%) patients. The median neutrophil and lymphocyte count were 2.70 (1.84-3.27) ×109/L and (1.52±0.53) ×109/L respectively. The mean C-reactive protein level was 19.11±17.39 mg/L. Patients were likely had normal procalcitonin, creatinine, alanine aminotransferase, creatine kinase and lactate dehydrogenase levels at diagnosis. Fourteen (87.50%) patients had pneumonia in chest CT scan. Conclusions No specific symptom was helpful in the diagnosis of 2019-nCoV infection, but relatively low WBC and lymphocyte level might be suggestive to diagnosis. Most patients had fever and pneumonia, however, there were indeed some patients without fever and pneumonia. Screening procedure should not only focus on fever patients. The origin, transmission route, key targets of the virus and mechanism of infection deserved more studies.


title: How to get out: ssRNA enveloped viruses and membrane fission

text: Enveloped viruses acquire their membrane from the host cell and accordingly need to separate their envelope from cellular membranes via membrane fission. Although some of the enveloped viruses recruit the endosomal sorting complex required for transport (ESCRT) to catalyze the final fission reaction, many enveloped viruses seem to bud in an ESCRT-independent manner. Here we describe the principles that govern membrane fission reactions in general and review progress in the understanding of ESCRT-mediated membrane fission. We relate ESCRT function to budding of single stranded RNA viruses and discuss alternative ways to mediate membrane fission that may govern ESCRT-independent budding.


title: Covid-19 Pandemic: What Changes for Dentists and Oral Medicine Experts? A Narrative Review and Novel Approaches to Infection Containment

text: The authors performed a narrative review on Severe Acute Respiratory Syndrome- CoronaVirus-2 ( SARS-CoV-2) and all infectious agents with the primary endpoints to illustrate the most accepted models of safety protocols in dentistry and oral medicine, and to propose an easy view of the problem and a comparison (pre- vs post-COVID19) for the most common dental procedures. The outcome is forecast to help dentists to individuate for a given procedure the differences in terms of safety protocols to avoid infectious contagion (by SARS-CoV-2 and others dangerous agents). An investigation was performed on the online databases Pubmed and Scopus using a combination of free words and Medical Subject Headings (MESH) terms: “dentist” OR “oral health” AND “COVID-19” OR “SARS-CoV-2” OR “coronavirus-19”. After a brief excursus on all infectious agents transmittable at the dental chair, the authors described all the personal protective equipment (PPE) actually on the market and their indications, and on the basis of the literature, they compared (before and after COVID-19 onset) the correct safety procedures for each dental practice studied, underlining the danger of underestimating, in general, dental cross-infections. The authors have highlighted the importance of knowing exactly the risk of infections in the dental practice, and to modulate correctly the use of PPE, in order to invest adequate financial resources and to avoid exposing both the dental team and patients to preventable risks.


Potential challenges in managing obstetric patients with COVID-19


title: Guidelines for the management of hospital-acquired pneumonia in the UK: Report of the Working Party on Hospital-Acquired Pneumonia of the British Society for Antimicrobial Chemotherapy

text: These evidence-based guidelines have been produced after a systematic literature review of a range of issues involving prevention, diagnosis and treatment of hospital-acquired pneumonia (HAP). Prevention is structured into sections addressing general issues, equipment, patient procedures and the environment, whereas in treatment, the structure addresses the use of antimicrobials in prevention and treatment, adjunctive therapies and the application of clinical protocols. The sections dealing with diagnosis are presented against the clinical, radiological and microbiological diagnosis of HAP. Recommendations are also made upon the role of invasive sampling and quantitative microbiology of respiratory secretions in directing antibiotic therapy in HAP/ventilator-associated pneumonia.


title: Transmission dynamics and control of Ebola virus disease (EVD): a review

text: The complex and unprecedented Ebola epidemic ongoing in West Africa has highlighted the need to review the epidemiological characteristics of Ebola Virus Disease (EVD) as well as our current understanding of the transmission dynamics and the effect of control interventions against Ebola transmission. Here we review key epidemiological data from past Ebola outbreaks and carry out a comparative review of mathematical models of the spread and control of Ebola in the context of past outbreaks and the ongoing epidemic in West Africa. We show that mathematical modeling offers useful insights into the risk of a major epidemic of EVD and the assessment of the impact of basic public health measures on disease spread. We also discuss the critical need to collect detailed epidemiological data in real-time during the course of an ongoing epidemic, carry out further studies to estimate the effectiveness of interventions during past outbreaks and the ongoing epidemic, and develop large-scale modeling studies to study the spread and control of viral hemorrhagic fevers in the context of the highly heterogeneous economic reality of African countries.


docid: jereueeg

title: Diffuse Alveolar Hemorrhage in a Patient Receiving Bevacizumab for Lung Cancer


title: The ocular surface, coronaviruses and COVID‐19

text: The ocular surface has been suggested as a site of infection with Coronavirus‐2 (SARS‐CoV‐2) responsible for the coronavirus disease‐19 (COVID‐19). This review examines the evidence for this hypothesis, and its implications for clinical practice. Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2), responsible for the COVID‐19 pandemic, is transmitted by person‐to‐person contact, via airborne droplets, or through contact with contaminated surfaces. SARS‐CoV‐2 binds to angiotensin converting enzyme‐2 (ACE2) to facilitate infection in humans. This review sets out to evaluate evidence for the ocular surface as a route of infection. A literature search in this area was conducted on 15 April 2020 using the Scopus database. In total, 287 results were returned and reviewed. There is preliminary evidence for ACE2 expression on corneal and conjunctival cells, but most of the other receptors to which coronaviruses bind appear to be found under epithelia of the ocular surface. Evidence from animal studies is limited, with a single study suggesting viral particles on the eye can travel to the lung, resulting in very mild infection. Coronavirus infection is rarely associated with conjunctivitis, with occasional cases reported in patients with confirmed COVID‐19, along with isolated cases of conjunctivitis as a presenting sign. Coronaviruses have been rarely isolated from tears or conjunctival swabs. The evidence suggests coronaviruses are unlikely to bind to ocular surface cells to initiate infection. Additionally, hypotheses that the virus could travel from the nasopharynx or through the conjunctival capillaries to the ocular surface during infection are probably incorrect. Conjunctivitis and isolation of the virus from the ocular surface occur only rarely, and overwhelmingly in patients with confirmed COVID‐19. Necessary precautions to prevent person‐to‐person transmission should be employed in clinical practice throughout the pandemic, and patients should be reminded to maintain good hygiene practices.


title: Religion as a Health Promoter During the 2019/2020 COVID Outbreak: View from Detroit

text: The 2019/2020 COVID outbreak has surfaced as a global pandemic. The news has carried stories of the heroic efforts of medical and other health practitioners, with public health officials charting the course of spread. In an urban center like Detroit, the generosity of everyday citizens and church organizations has also played an important role. This inspection of the pandemic from the view of Detroit will examine the epidemiology of the coronavirus, translation of professional practice into people’s awareness of the chronic disease risk factors which are prevalent in Detroit, moral and ethical views on the distribution of resources, and three major ways that religious faith has helped to sustain people’s health and welfare in the midst of the broad social challenges posed by this novel coronavirus.


docid: hucwnvef

title: Chinese Bioethicists Speak Out on Covid‐19, and Others Follow

text: Shortly after Wuhan, the city where the novel coronavirus was first identified, was placed on lockdown in January, I received an email from two Hastings Center fellows in China: Renzong Qiu, of Renmin University of China in Beijing, and Ruipeng Lei, of Huazhong University of Science and Technology in Wuhan. Attached was a post for our blog, Hastings Bioethics Forum, that raised ethical and legal questions about China's response. “Hegel says, ‘We learn from history that we do not learn from history,’” their piece began. “The recurrence of the coronavirus epidemic in China proves his insight to be right.” This bold report from bioethicists in China was courageous and eye‐opening. It was among the first discussions in bioethics of what has since become a global crisis, and it turned out to be the first in a string of commentaries in Hastings Bioethics Forum with insights about the crisis, the issues it raises, and how the world should respond to it.


title: miR‐193b represses influenza A virus infection by inhibiting Wnt/β‐catenin signalling

text: Due to an increasing emergence of new and drug‐resistant strains of the influenza A virus (IAV), developing novel measures to combat influenza is necessary. We have previously shown that inhibiting Wnt/β‐catenin pathway reduces IAV infection. In this study, we aimed to identify antiviral human microRNAs (miRNAs) that target the Wnt/β‐catenin signalling pathway. Using a miRNA expression library, we identified 85 miRNAs that up‐regulated and 20 miRNAs that down‐regulated the Wnt/β‐catenin signalling pathway. Fifteen miRNAs were validated to up‐regulate and five miRNAs to down‐regulate the pathway. Overexpression of four selected miRNAs (miR‐193b, miR‐548f‐1, miR‐1‐1, and miR‐509‐1) that down‐regulated the Wnt/β‐catenin signalling pathway reduced viral mRNA, protein levels in A/PR/8/34‐infected HEK293 cells, and progeny virus production. Overexpression of miR‐193b in lung epithelial A549 cells also resulted in decreases of A/PR/8/34 infection. Furthermore, miR‐193b inhibited the replication of various strains, including H1N1 (A/PR/8/34, A/WSN/33, A/Oklahoma/3052/09) and H3N2 (A/Oklahoma/309/2006), as determined by a viral reporter luciferase assay. Further studies revealed that β‐catenin was a target of miR‐193b, and β‐catenin rescued miR‐193b‐mediated suppression of IAV infection. miR‐193b induced G0/G1 cell cycle arrest and delayed vRNP nuclear import. Finally, adenovirus‐mediated gene transfer of miR‐193b to the lung reduced viral load in mice challenged by a sublethal dose of A/PR/8/34. Collectively, our findings suggest that miR‐193b represses IAV infection by inhibiting Wnt/β‐catenin signalling.


title: Modulatory effects of ammonia-N on the immune system of Penaeus japonicus to virulence of white spot syndrome virus

text: Abstract To study response to white spot syndrome virus (WSSV) under ammonia stress, Penaeus japonicus were exposed to 5 mg l−1 ammonia-N and challenged orally with WSSV (NW). Controls consisted of an ammonia-N-exposed control group (N), a WSSV-challenged positive control group (W), and an untreated control group (control). Immune parameters measured were total haemocyte count (THC), haemocyte phagocytosis, plasma protein content and haemolymph enzymatic activities for prophenoloxidase (proPO), alkaline phosphatase (ALP), and nitric oxide synthase (NOS). THC and plasma protein had downward trends with time in all treatment groups (NW, N, and W) in contrast to the untreated control group (control). The percentage phagocytosis, NOS activity, and ALP and proPO activity of W and NW decreased initially then increased from 6 to 78 h (except for NOS and ALP, from 6 to 54 h) before declining thereafter until the end of the experiment. Compared with untreated controls (control), there was a downward trend for all measured parameters in the treatment groups (N, NW, and W), but the degree was W>NW>N. WSSV was detected at 78 h postchallenge in both W and NW. In conclusion, 5 mg l−1 ammonia-N reduced the immunocompetence of P. japonicus and may have decreased the virulence of WSSV.


title: Common Adverse Events Associated with the Use of Ribavirin for Severe Acute Respiratory Syndrome in Canada

text: Although information on efficacy and adverse drug reactions is lacking, ribavirin has been used empirically for the treatment of severe acute respiratory syndrome (SARS). We report common adverse events in 110 patients with suspected or probable SARS who were treated with ribavirin. Sixty-one percent of the patients had evidence of hemolytic anemia, and hypocalcemia and hypomagnesmia were reported in 58% and 46% of patients, respectively.


title: Upper airway viruses and bacteria detection in clinical pneumonia in a population with high nasal colonisation do not relate to clinical signs

text: Indigenous Australian children have high (up to 90%) rates of nasopharyngeal microbial colonisation and of hospitalisation for pneumonia. In Indigenous children hospitalised with pneumonia in Central Australia, we describe the nasopharyngeal detection of viruses and bacteria and assessed whether their presence related to signs of pneumonia (tachypnoea and/or chest in-drawing) on hospital admission and during subsequent days. Nasopharyngeal swabs (NPS) and data were prospectively collected from 145 children (median age = 23.5 months, interquartile range [IQR] 8.7–50) hospitalised with pneumonia at Alice Springs Hospital, Australia, between April 2001 and July 2002. The cohort was enrolled in a randomised controlled study using zinc and/or vitamin A supplementation. NPS were taken within 24 hours of hospitalisation and kept frozen at-80°C until analysed in 2014. Polymerase chain reaction (PCR) was used to detect Moraxella catarrhalis, Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus, Chlamydophila pneumoniae, Mycoplasma pneumoniae, and 16 respiratory viruses. Uni- and multi-variate analyses were used to examine the relationships. One or more organisms were present in 137 (94.5%) NPS; 133 (91.7%) detected ≥ 1 bacterium, 34 (37.2%) for ≥ 1 virus and 50 (34.5%) were positive for both viruses and bacteria. C. pneumoniae (n = 3) and M. pneumoniae (n = 2) were rare. In multi-variate analyses, age < 12 months (odds ratio [OR] 6.6 [95% confidence interval {CI} 1.7–25.4]) and fever (OR 4.1 [95% CI 1.7–10.4]) were associated with tachypnoea and chest in-drawing. However the presence of bacteria and/or virus type was not associated with tachypnoea and/or chest in-drawing on admission or during recovery. In children with high nasopharyngeal microbial colonisation rates, the utility of NPS in determining the diagnosis of clinical pneumonia or duration of tachypnoea or in-drawing is likely limited. Larger cohort and case-control studies are required to confirm our findings.


title: The release into the environment of genetically engineered viruses, vaccines and viral pesticides

text: Abstract Viruses are being developed by genetic engineering procedures for two purposes: as improved vaccines or vectors for inserting foreign genes into a vaccinated hosts, and as improved viral pesticides. Both uses raise environmental issues.


title: Paper alert Coronavirus Disease 2019 Return to Work Guidance and Recommendations for Vestibular Clinicians

text: As states begin issuing progressive deconfinement guidelines, hospitals and institutions are starting to reopen for elective procedures and consultations Vestibular clinicians are opening their practices to evaluate, test, or treat patients with dizziness and balance problems The following document, requested by the American Balance Society, collates the current information about the virus, including transmission from asymptomatic carriers, decontamination, and other safety protocols, and provides a return to work guidance for clinicians caring for this population of patients, promoting provider, patient, and staff safety


title: Human genomics and preparedness for infectious threats

text: Public health preparedness requires effective surveillance of and rapid response to infectious disease outbreaks. Inclusion of research activities within the outbreak setting provides important opportunities to maximize limited resources, to enhance gains in scientific knowledge, and ultimately to increase levels of preparedness. With rapid advances in laboratory technologies, banking and analysis of human genomic specimens can be conducted as part of public health investigations, enabling valuable research well into the future.


title: Proteolytic Disassembly Is a Critical Determinant for Reovirus Oncolysis

text: See page 1406 Mammalian ortheoreoviruses are currently being investigated as novel cancer therapeutics, but the cellular mechanisms that regulate susceptibility to reovirus oncolysis remain poorly understood. In this study, we present evidence that virion disassembly is a key determinant of reovirus oncolysis. To penetrate cell membranes and initiate infection, the outermost capsid proteins of reovirus must be proteolyzed to generate a disassembled particle called an infectious subviral particle (ISVP). In fibroblasts, this process is mediated by the endo/lysosomal proteases cathepsins B and L. We have analyzed the early events of infection in reovirus-susceptible and -resistant cells. We find that, in contrast to susceptible glioma cells and Ras-transformed NIH3T3 cells, reovirus-resistant cancer cells and untransformed NIH3T3 cells restrict virion uncoating and subsequent gene expression. Disassembly-restrictive cells support reovirus infection, as in vitro-generated ISVPs establish productive infection, and pretreatment with poly(I:C) does not prevent infection in cancer cells. We find that the level of active cathepsin B and L is increased in tumors and that disassembly-restrictive glioma cells support reovirus oncolysis when grown as a tumor in vivo. Together, these results provide a model in which proteolytic disassembly of reovirus is a critical determinant of susceptibility to reovirus oncolysis.


Human Bocavirus in Febrile Children, the Netherlands


title: The molecular epidemiology of respiratory viruses in military trainees in Iran

text: Background: Military populations are more prone to respiratory infections worldwide. There is a dearth of research about the role of viral pathogens in the etiology of respiratory infections in military trainees in Iran. Hence, we aimed to investigate the molecular epidemiology and clinical symptoms of respiratory viruses among this population. Methods: This cross-sectional study was performed on 400 military trainees with symptoms of respiratory infection, referred to the military medical clinic center in the basic military training camp of the General Staff of the Armed Forces of the Islamic Republic of Iran. Nucleic acid extraction from the throat or nasopharyngeal swab samples was performed by an automated extraction system. The extracts were then analyzed by the CLART® PneumoVir array system for the detection of respiratory viruses. Results: All military trainees were male, aged between 18 and 57 years (mean: 21.69 years). Sore throat (75.5%), rhinorrhea (63.2%), cough (59.2%), fever (59.2%), and nasal congestion (50.5%) were amongst the most common symptoms. Overall, viral pathogens were detected in a total count of 124 (31%). The most commonly detected viruses were rhinovirus (7.2%), respiratory syncytial virus A (7.2%) and influenza B virus (6%). Conclusion: This study was an important first step for understanding the etiological role of viral pathogens in respiratory infection among military trainees population in Iran. Our results indicated that rhinovirus, respiratory syncytial virus A and influenza B virus are important viral pathogens causing respiratory infection in military trainees, respectively. However, further multi-center studies with larger sample size are strongly recommended to confirm our findings.


docid: vjfquvlu

title: Genomic characterization of a novel SARS-CoV-2

text: Abstract A new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associated with human to human transmission and extreme human sickness has been as of late announced from the city of Wuhan in China. Our objectives were to mutation analysis between recently reported genomes at various times and locations and to characterize the genomic structure of SARS-CoV-2 using bioinformatics programs. Information on the variation of viruses is of considerable medical and biological impacts on the prevention, diagnosis, and therapy of infectious diseases. To understand the genomic structure and variations of the SARS-CoV-2. The study analyzed 95 SARS-CoV-2 complete genome sequences available in GenBank, National MicrobiologyData Center (NMDC) and NGDC Genome Warehouse from December-2019 until 05 of April-2020. The genomic signature analysis demonstrates that a strong association between the time of sample collection, location of sample and accumulation of genetic diversity. We found 116 mutations, the three most common mutations were 8782C>T in ORF1ab gene, 28144T>C in ORF8 gene and 29095C>T in the N gene. The mutations might affect the severity and spread of the SARS-CoV-2. The finding heavily supports an intense requirement for additional prompt, inclusive investigations that combine genomic detail, epidemiological information and graph records of the clinical features of patients with COVID-19.


Convalescent plasma therapy in the treatment of COVID-19: some considerations: correspondence


title: Human T-cell immunity against the emerging and re-emerging viruses

text: Over the past decade, we have seen an alarming number of high-profile outbreaks of newly emerging and re-emerging viruses. Recent outbreaks of avian influenza viruses, Middle East respiratory syndrome coronaviruses, Zika virus and Ebola virus present great threats to global health. Considering the pivotal role of host T-cell immunity in the alleviation of symptoms and the clearance of viruses in patients, there are three issues to be primarily concerned about T-cell immunity when a new virus emerges: first, does the population possess pre-existing T-cells against the new virus through previous infections of genetically relevant viruses; second, does a proper immune response arise in the patients to provide protection through an immunopathogenic effect; lastly, how long can the virus-specific immune memory persist. Herein, we summarize the current updates on the characteristics of human T-cell immunological responses against recently emerged or re-emerged viruses, and emphasize the necessity for timely investigation on the T-cell features of these viral diseases, which may provide beneficial recommendations for clinical diagnosis and vaccine development.


title: Serial Interval of COVID-19 among Publicly Reported Confirmed Cases

text: We estimate the distribution of serial intervals for 468 confirmed cases of coronavirus disease reported in China as of February 8, 2020. The mean interval was 3.96 days (95% CI 3.53–4.39 days), SD 4.75 days (95% CI 4.46–5.07 days); 12.6% of case reports indicated presymptomatic transmission.


title: Tumour Necrosis Factor Gene Polymorphism and Disease Prevalence

text: Tumour necrosis factor (TNF), an important proinflammatory cytokine, plays a role in the regulation of cell differentiation, proliferation and death, as well as in inflammation, innate and adaptive immune responses, and also implicated in a wide variety of human diseases. The presence of DNA sequence variations in regulatory region might interfere with transcription of TNF gene, influencing the circulating level of TNF and thus increases the susceptibility to human diseases (infectious, cancer, autoimmune, neurodegenerative and other diseases). In this review, we have comprehensively analysed various published case–control studies of different types of human diseases, in which TNF gene polymorphism played a role, and computationally predicted several single nucleotide polymorphisms (SNPs) lie in transcription factor–binding sites (TFBS) of transcription factors (TFs). It has been observed that TNF enhancer polymorphism is implicated in several diseases, and TNF rs1800629 and rs361525 SNPs are the most important in human disease susceptibility as these might influence the transcription of TNF gene. Thirty‐two SNPs lies in TFBS of 20 TFs have been detected in the TNF upstream region. It has been found that TNF enhancer polymorphism influences the serum level of TNF in different human diseases and thus affects the susceptibility to diseases. The presence of DNA sequence variation in TNF gene causes the modification of transcriptional regulation and thus responsible for association of susceptibility/resistance with human diseases.


title: Children in Critical Care Due to Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Experience in a Spanish Hospital

text: Spain has been one of the countries most severely affected by the coronavirus disease 2019. This study aims to describe a series of children admitted to a PICU due to coronavirus disease 2019 infection. DESIGN: Prospective observational study. SETTING: Tertiary hospital in Madrid, Spain. PATIENTS: Children admitted to the PICU with severe acute respiratory syndrome coronavirus 2 (severe acute respiratory syndrome coronavirus 2) infection, from March 1, 2020, to April 15, 2020. INTERVENTIONS: Observational study. MEASUREMENTS AND MAIN RESULTS: Epidemiologic data, previous clinical characteristics, support therapy needed, imaging tests, laboratory observations on admission, and pharmacologic therapy. Eleven children were admitted to the PICU, with suspected coronavirus disease 2019; the polymerase chain reaction test was positive in seven. The median age was 100.7 months (range, 0.5–162). Five were admitted from the emergency department and two from the ward. The Pediatric Sequential Organ Failure Assessment score was 3 (range, 0–9), and Pediatric Risk of Mortality II score was 4 (range, 0–16). All children were previously healthy except one (allogeneic hematopoietic stem cell transplantation). Respiratory symptoms and fever were prevalent. A chest radiograph led to a pneumonia diagnosis. Not all patients presented with lymphopenia on admission. d-Dimer and ferritin were elevated. All patients needed oxygen therapy through a nasal cannula; five patients received high-flow nasal cannula therapy, which was later substituted with noninvasive ventilation in four. Mechanical ventilation was necessary in two patients on the first day of PICU admission. Two children required mechanical ventilation and inotropic support. Tocilizumab was applied in two intubated children. Also, four children received heparin. No patients died. CONCLUSIONS: On the whole, the children were previously healthy and are more than 1 year old. Respiratory symptoms were the leading cause of PICU admission, making respiratory support the principal therapy. Patients requiring mechanical ventilation showed deterioration on the first day of admission. These children seemed to require close monitoring, and multicenter studies are necessary.


title: The effects of high performance work systems in employees’ service-oriented OCB

text: The present research investigates the effects of “High Performance Work Systems (HPWS)” on employees’ “work engagement” and “service-oriented Organizational Citizenship Behavior (OCB)”, through the development of a social and justice climate. In doing so, “Partial Least Squares Structural Equation Modeling (PLS-SEM)” was applied based on a convenient sample of 448 customer-contact hotel employees across ten Greek hotel organizations. In summary, the study reveals first the valuable contribution of HPWS towards the development of a justice and service climate, which in turn influence positively employees’ work engagement. As a consequence, employees respond by exhibiting extra role behaviors and by engaging in service-oriented OCB. Overall, the findings clarify the mechanism behind the HPWS process, known as the “black-box”, a valuable knowledge for professionals practicing Human Resource Management (HRM).


title: PDGF and FGF2 regulate oligodendrocyte progenitor responses to demyelination

text: Acute demyelination of adult CNS, resulting from trauma or disease, is initially followed by remyelination. However, chronic lesions with subsequent functional impairment result from eventual failure of the remyelination process, as seen in multiple sclerosis. Studies using animal models of successful remyelination delineate a progression of events facilitating remyelination. A universal feature of this repair process is extensive proliferation of oligodendrocyte progenitor cells (OPs) in response to demyelination. To investigate signals that regulate OP proliferation in response to demyelination we used murine hepatitis virus‐A59 (MHV‐A59) infection of adult mice to induce focal demyelination throughout the spinal cord followed by spontaneous remyelination. We cultured glial cells directly from demyelinating and remyelinating spinal cords using conditions that maintain the dramatically enhanced OP proliferative response prior to CNS remyelination. We identify PDGF and FGF2 as significant mitogens regulating this proliferative response. Furthermore, we demonstrate endogenous PDGF and FGF2 activity in these glial cultures isolated from demyelinated CNS tissue. These findings correlate well with our previous demonstration of increased in vivo expression of PDGF and FGF2 ligand and corresponding receptors in MHV‐A59 lesions. Together these studies support the potential of these pathways to function in vivo as critical factors in regulating remyelination. © 2003 Wiley Periodicals, Inc. J Neurobiol 54: 457–472, 2003


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