title: Management of Pemphigus in COVID-19 Pandemic Era; a Review Article

text: The novel coronavirus is rapidly spreading around the world. Since the public announcement of the COVID-19 outbreak, several concerns have been raised by dermatologists as well as pemphigus patients who take immunosuppressive drugs. In this paper, we review the literature about the common treatment of pemphigus with a focus on the lessons from similar epidemics to find a proper suggestion to manage pemphigus in the COVID-19 pandemic era. The effect of many of the drugs used for treatment of Pemphigus vulgaris (PV) on COVID-19 is not clear. We also do not have data on the impact of this autoimmune disease, which may involve the mucous membranes, on the acquisition or course of COVID-19. We are currently in the midst of a pandemic and evaluating the effect of COVID-19 on the population of susceptible patients suffering from auto-immune diseases like pemphigus is essential. The evidence on best ways to manage patients with underlying conditions, such as pemphigus, during the outbreak of COVID-19 is evolving and the data is updated every day.


title: CD133作为肺癌干细胞标记物的应用及其局限性

text: Lung cancer is one of the most common tumor, which lacks of effective clinical treatment to lead to desirable prognosis. According to cancer stem cell hypothesis, lung cancer stem cells are considered to be responsible for carcinogenesis, development, metastasis, recurrence, invasion, resistance to chemotherapy and radiotherapy of lung cancer. In recent years, more and more institutes used glycosylated CD133 epitopes to define, isolate, purify lung cancer stem cells. However, along with deeply research, the application of CD133 epitopes in lung cancer stem cell research is questioned. The utilization and limitation of CD133 epitopes in lung cancer stem cells research for the past few years is summaried in this review.


docid: afcjqjdj

title: Reply to correspondence: Vaginal Delivery in a Woman Infected With SARS-CoV-2 - The First Case Reported in Portugal


title: Managing Cancer Care during the COVID-19 Pandemic and Beyond

text: Abstract COVID-19 pandemic has posed insurmountable challenges to health care systems globally. Cancer therapy is complex, and outcomes are centered on timing. Many oncology societies and health ministries have issued guidelines for cancer care to enable oncologists and patients navigate the crisis. Lessons learned should inform care models for future pandemics.


title: Multihospital Outbreak of a Middle East Respiratory Syndrome Coronavirus Deletion Variant, Jordan: A Molecular, Serologic, and Epidemiologic Investigation

text: BACKGROUND: An outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in Jordan in 2015 involved a variant virus that acquired distinctive deletions in the accessory open reading frames. We conducted a molecular and seroepidemiologic investigation to describe the deletion variant’s transmission patterns and epidemiology. METHODS: We reviewed epidemiologic and medical chart data and analyzed viral genome sequences from respiratory specimens of MERS-CoV cases. In early 2016, sera and standardized interviews were obtained from MERS-CoV cases and their contacts. Sera were evaluated by nucleocapsid and spike protein enzyme immunoassays and microneutralization. RESULTS: Among 16 cases, 11 (69%) had health care exposure and 5 (31%) were relatives of a known case; 13 (81%) were symptomatic, and 7 (44%) died. Genome sequencing of MERS-CoV from 13 cases revealed 3 transmissible deletions associated with clinical illness during the outbreak. Deletion variant sequences were epidemiologically clustered and linked to a common transmission chain. Interviews and sera were collected from 2 surviving cases, 23 household contacts, and 278 health care contacts; 1 (50%) case, 2 (9%) household contacts, and 3 (1%) health care contacts tested seropositive. CONCLUSIONS: The MERS-CoV deletion variants retained human-to-human transmissibility and caused clinical illness in infected persons despite accumulated mutations. Serology suggested limited transmission beyond that detected during the initial outbreak investigation.


title: Porcine adenovirus as a delivery system for swine vaccines and immunotherapeutics

text: Abstract Porcine adenovirus (PAdV) has many qualities which make it an ideal choice for use as a delivery vector in swine. It is a low grade pathogen, present almost world-wide in a number of serotypes varying in their virulence and tissue tropism, which may allow for serotype specific vaccine targeting. PAdV is species specific having only been isolated from swine, reducing the possibility of its spread to other animals or man following administration. When engineered to contain a foreign gene, recombinant PAdV (rPAdV) can be grown to high titres in tissue culture cells making it cheap to produce. Knowledge of the complete nucleotide sequence of the PAdV genome has enabled rationally directed insertions of foreign genes which remain stably inserted in the genome and can be expressed at high levels following delivery to the target host. Importantly, recombinant PAdV can be administered by injection or by the oral route in feed or drinking water. We have delivered a range of antigens and immunomodulatory molecules to commercially available pigs using rPAdV and found it to be a very effective delivery system. Significantly, recombinant PAdV serotype 3 is highly effective as a delivery vehicle even when administered in the face of high levels of artificially induced serotype specific neutralising antibody to the vector.


title: II n’y a pas de parallélisme entre les susceptibilités bactériologiques in vitro et la réponse clinique après une cure antibiotique intraveineuse dans la mucoviscidose A.L. Smith

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title: Antibodies to coronaviruses are higher in older compared with younger adults and binding antibodies are more sensitive than neutralizing antibodies in identifying coronavirus‐associated illnesses

text: Human coronaviruses (HCoV) are common causes of respiratory illnesses (RI) despite preexisting humoral immunity. Sera were obtained near the onset of RI and 3 to 4 weeks later as part of a prospective study of 200 subjects evaluated for RI from 2009 to 2013. Antibodies against common HCoV strains were measured by enzyme‐linked immunosorbent assay and neutralization assay comparing older adults with cardiopulmonary diseases (99 subjects) to younger, healthy adults (101 subjects). Virus shedding was detected in respiratory secretions by polymerase chain reaction. Of 43 HCoV‐associated illnesses, 15 (35%) occurred in 14 older adults (aged ≥60 years) and 28 (65%) in 28 younger adults (aged 21‐40 years). Binding and neutralizing antibodies were higher in older adults. Only 16 (35.7%) of RI with increases in binding antibodies also had increases in neutralizing antibodies to HCoV. Increases in binding antibodies with RI were more frequent than increased neutralizing antibodies and virus shedding, and more frequent in younger compared to older adults. Functional neutralizing antibodies were not stimulated as often as binding antibodies, explaining in part a susceptibility to reinfection with HCoV. Monitoring binding antibodies may be more sensitive for the serologic detection of HCoV infections.


title: Molecular methods for pathogen and microbial community detection and characterization: Current and potential application in diagnostic microbiology

text: Abstract Clinical microbiology laboratories worldwide have historically relied on phenotypic methods (i.e., culture and biochemical tests) for detection, identification and characterization of virulence traits (e.g., antibiotic resistance genes, toxins) of human pathogens. However, limitations to implementation of molecular methods for human infectious diseases testing are being rapidly overcome allowing for the clinical evaluation and implementation of diverse technologies with expanding diagnostic capabilities. The advantages and limitation of molecular techniques including real-time polymerase chain reaction, partial or whole genome sequencing, molecular typing, microarrays, broad-range PCR and multiplexing will be discussed. Finally, terminal restriction fragment length polymorphism (T-RFLP) and deep sequencing are introduced as technologies at the clinical interface with the potential to dramatically enhance our ability to diagnose infectious diseases and better define the epidemiology and microbial ecology of a wide range of complex infections.


title: Risk factors for a poor outcome among children admitted with clinically severe pneumonia to a university hospital in Rabat, Morocco

text: Summary Objectives Data on prognostic factors among children with severe pneumonia are scarce in middle-income countries. We investigated prognostic factors for an adverse outcome among children admitted to the Hôpital d’Enfants de Rabat, Morocco with World Health Organization-defined clinically severe pneumonia (CSP). Methods Children aged 2–59 months admitted to the hospital and fulfilling the CSP definition were recruited into this 13-month prospective study. A poor prognosis was defined as death, a need for intensive care, or a Respiratory Index of Severity in Children (RISC) score ≥3. Multivariate logistic regression was performed to ascertain independent predictive factors for a poor prognosis. Results Of the 689 children included in this analysis, 55 (8.0%) required intensive care and 28 died (4.0%). Five hundred and two (72.8%) children were classified as having a good prognosis and 187 (27.2%) as having a poor prognosis. A history of prematurity (odds ratio (OR) 2.50, 95% confidence interval (CI) 1.24–5.04), of fever (OR 2.25, 95% CI 1.32–3.83), living in a house with smokers (OR 1.79, 95% CI 1.18–2.72), impaired consciousness (OR 10.96, 95% CI 2.88–41.73), cyanosis (OR 2.09, 95% CI 1.05–4.15), pallor (OR 2.27, 95% CI 1.34–3.84), having rhonchi on auscultation (OR 2.45, 95% CI 1.58–3.79), and human metapneumovirus infection (OR 2.13, 95% CI 1.13–4.02) were all independent risk factors for an adverse outcome, whereas a history of asthma (OR 0.46, 95% CI 0.25–0.84) was the only independent risk factor for a positive outcome. Conclusions The early identification of factors associated with a poor prognosis could improve management strategies and the likelihood of survival of Moroccan children with severe pneumonia.


title: Identification of coronavirus sequences in carp cDNA from Wuhan, China

text: Severe acute respiratory syndrome (SARS)‐like coronavirus sequences were identified in two separate complementary DNA (cDNA) pools. The first pool was from a Carassius auratus (crusian carp) cell line and the second was from Ctenopharyngodon idella (grass carp) head kidney tissue. BLAST analysis suggests that these sequences belong to SARS‐like coronaviruses, and that they are not evolutionarily conserved in other species. Investigation of the submitting laboratories revealed that two laboratories from the Institute of Hydrobiology at the Chinese Academy of Sciences in Wuhan, China performed the research and submitted the cDNA libraries to GenBank. This institution is very close in proximity to the Wuhan South China Seafood Wholesale Market where SARS‐CoV‐2 first amplified in the human population. It is possible that these sequences are an artifact of the bioinformatics pipeline that was used. It is also possible that SARS‐like coronaviruses are a common environmental pathogen in the region that may be in aquatic habitats.


title: The Neurobiology of Social Distance

text: Abstract Never before have we experienced social isolation on such a massive scale as we have in response to COVID-19. Yet we know that the social environment has a dramatic impact on our sense of life satisfaction and well-being. In times of distress, crisis, or disaster, human resilience depends on the richness and strength of social connections, as well as active engagement in groups and communities. Over recent years, evidence emerging from various disciplines has made it abundantly clear: loneliness may be the most potent threat to survival and longevity. Here, we highlight the benefits of social bonds, choreographies of bond creation and maintenance, as well as the neurocognitive basis of social isolation and its deep consequences for mental and physical health.


title: Post-SARS infection control in the hospital and clinic

text: Summary The recent severe acute respiratory syndrome (SARS) outbreak has almost mandated a re-evaluation of infection control practices in hospitals, clinics, schools and domestic environments, especially for patients with respiratory tract symptoms. Triage, early case detection followed by prompt isolation and quarantine are major preventive measures. Respiratory tract infections are the most common childhood illnesses and paediatric SARS poses special problems in diagnosis because of its non-specific presentation. The main lessons learnt from the outbreak were: (1) despite well established guidelines on infection control precautions, poor understanding of underlying principles and deficiencies in compliance are common among healthcare professionals, especially during emergencies; (2) even a slight lapse can be fatal; and (3) over-protection can be counterproductive. Hence it is important to: (1) be protected to protect others; (2) be vigilant and prepared for emerging infections; (3) be proficient and scrupulous in infection control measures; (4) be apposite and practical on personal protective equipments to ensure sustainability; and (5) be dutiful and prompt in informing of potential threats and work closely with others.


title: A Feminist Perspective on COVID‐19 and the Value of Care Work Globally

text: The shared response to the COVID‐19 crisis demonstrates that the vast majority of society believes human well‐being ‐ not economic growth ‐ should be at the center of policy. COVID‐19 exposes the foundational role of care work, both paid and unpaid, to functioning societies and economies. Focusing on "production" instead of the sustainable reproduction of human life devalues care work and those who perform it. Women's physical and mental health, and the societies that rely on them, are at stake. When these policies are formulated, the field of feminist economics has valuable lessons for mitigating hardships as countries navigate the related economic fallout. A comprehensive response to the COVID‐19 crisis must recognize this gendered work as an integral part of the economic system that promotes human well‐being for all.


title: Low-level Circulation of Enterovirus D68–Associated Acute Respiratory Infections, Germany, 2014

text: We used physician sentinel surveillance to identify 25 (7.7%) mild to severe infections with enterovirus D68 (EV-D68) in children and adults among 325 outpatients with acute respiratory infections in Germany during August–October 2014. Results suggested low-level circulation of enterovirus D68 in Germany. Viruses were characterized by sequencing viral protein (VP) 1 and VP4/VP2 genomic regions.


docid: vzsdvrwo

title: Rewriting the rules for care of MDS and AML patients in the time of COVID-19

text: Abstract The care of patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) has been radically altered by COVID-19, especially in New York City, the epicenter of the pandemic. Here we summarize how telemedicine, virtual visits, delayed transfusions, and chemotherapy, preferably selecting self-administered medications and visits by home healthcare workers, are employed to minimize exposure of our high-risk population of patients to the virus. The unique challenges of transplants during the pandemic and the consequences of an abrupt halt in all non-essential research activities are described. Not all the changes forced by COVID-19 are detrimental.


title: Testing for SARS-CoV-2 (COVID-19): a systematic review and clinical guide to molecular and serological in-vitro diagnostic assays

text: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated Coronavirus disease 2019 (COVID-19) pandemic has demanded rapid upscaling of in-vitro diagnostic assays to enable mass screening and testing of high-risk groups, and simultaneous ascertainment of robust data on past SARS-CoV-2 exposure at an individual and population level. To meet the exponential demand in testing, there has been an accelerated development of both molecular and serological assays across a plethora of platforms. In the present review, we discuss the current literature on these modalities including the nucleic acid amplification tests, direct viral antigen tests and the rapidly expanding laboratory based and point of care serological tests. This suite of complementary tests will inform crucial decisions by healthcare providers and policy makers and understanding their strengths and limitations will be critical to their judicious application for the development of algorithmic approaches to treatment and public health strategies.


docid: fsoswzzk

title: Documento de consenso sobre el diagnóstico y tratamiento de la faringoamigdalitis aguda

text: Resumen La faringoamigdalitis aguda (FAA) es una de las enfermedades más comunes en la infancia. La etiología más frecuente es vírica. Entre las causas bacterianas, el principal agente responsable es Streptococcus pyogenes o estreptococo beta hemolítico del grupo A (EbhGA). Las escalas de valoración clínica son una buena ayuda para seleccionar a qué niños se deben practicar las técnicas de detección rápida de antígeno estreptocócico (TDR) y/o el cultivo de muestras faringoamigdalares. Sin su empleo, se tiende al sobrediagnóstico de FAA estreptocócica, con la consiguiente prescripción innecesaria de antibióticos, muchas veces de amplio espectro. Los objetivos del tratamiento son: acelerar la resolución de los síntomas, reducir el tiempo de contagio y prevenir las complicaciones supurativas locales y no supurativas. Idealmente, solo deben tratarse los casos confirmados. En caso de no disponibilidad de la TDR, o en algunos casos, ante un resultado negativo, se recomienda obtener cultivo e iniciar tratamiento a la espera de los resultados, solo si la sospecha clínica es alta. Los antibióticos de elección para el tratamiento de la FAA estreptocócica son penicilina y amoxicilina. Amoxicilina-clavulánico no está indicado de forma empírica en la infección aguda. Los macrólidos tampoco son un tratamiento de primera elección; su uso debe reservarse para pacientes con alergia inmediata a penicilina o como tratamiento erradicador, en los casos indicados. Es urgente y prioritario en nuestro país adecuar la prescripción de antibióticos a la evidencia científica disponible. Abstract Acute tonsillopharyngitis is one of the most common childhood diseases. Viruses are the most frequent origin. Group A Streptococcus (Streptococcus pyogenes) is the main bacterial cause. A culture or a rapid antigen-detection test of a throat-swab specimen should only be done on the basis of clinical scores, in order to avoid over-diagnosis of bacterial origin and unnecessary antibiotic prescription. The objectives of treatment are: the reduction of symptoms, reduce the contagious period, and prevent local suppurative and systemic complications. Ideally, only confirmed cases should receive antibiotics. If there is no possibility to perform a rapid antigen-detection test, or in some cases if the result is negative, it is recommended to perform a culture and, if there is high suspicious index, to prescribe antibiotics. Penicillin is the treatment of choice, although amoxicillin is also accepted as the first option. Amoxicillin/clavulanate is not indicated in any case as empirical treatment. Macrolides are not a first choice antibiotic, and should be reserved for those patients with immediate penicillin allergy reaction or for the treatment of streptococcal carriers. It is of primordial importance to adapt the prescribing of antibiotics to the scientific evidence.


title: The Stirling Protocol – Putting the environment at the heart of prosperity and social inclusion

text: Abstract While the global coronavirus crisis impacts society and the economy in a myriad of ways, it provides, what is likely to be, a once in a lifetime opportunity for us to rethink our response to climate change. According to the 2020 Global Risk Register, extreme weather and climate action failure are the two most likely and impactful risks to the global economy, which now more than ever needs to be avoided. Addressing the major challenges that we face from climate change can often appear to conflict with economic priorities. Add to this the fact that environmental mitigation steps can inadvertently exclude sections of the population and the enormity and complexity of climate change responses can result in paralysis. In contrast, the Stirling Protocol provides the framework for rapid, effective action and comprises three pillars: Environment, Economy & Inclusion. By addressing and balancing these three pillars, the simple protocol can be adopted throughout organisations putting the environment at the heart of sustainable prosperity and inclusion and provide a benchmark for positive action.


A multipurpose portable negative air flow isolation chamber for aerosol generating medical procedures during the COVID-19 pandemic


title: Phosphorylation events during viral infections provide potential therapeutic targets

text: For many medically relevant viruses, there is now considerable evidence that both viral and cellular kinases play important roles in viral infection. Ultimately, these kinases, and the cellular signaling pathways that they exploit, may serve as therapeutic targets for treating patients. Currently, small molecule inhibitors of kinases are under investigation as therapy for herpes viral infections. Additionally, a number of cellular or host-directed tyrosine kinase inhibitors that have been previously FDA-approved for cancer treatment are under study in animal models and clinical trials, as they have shown promise for the treatment of various viral infections as well. This review will highlight the wide range of viral proteins phosphorylated by viral and cellular kinases, and the potential for variability of kinase recognition sites within viral substrates to impact phosphorylation and kinase prediction. Research studying kinase-targeting prophylactic and therapeutic treatments for a number of viral infections will also be discussed.


title: Impact of the Autophagy Machinery on Hepatitis C Virus Infection

text: Autophagy is a cellular process that catabolizes cytoplasmic components and maintains energy homeostasis. As a stress response, the autophagy machinery interconnects a wide range of cellular pathways, enhancing the spread of certain pathogens while limiting others, and has become a highly active research area over the past several years. Independent laboratories have recently reported that autophagy vesicles accumulate in hepatitis C virus (HCV) infected cells and that autophagy proteins can function as proviral factors required for HCV replication. In this review, we summarize what is currently known about the interplay between autophagy and HCV and the possible mechanisms whereby autophagy proteins might favor HCV propagation.


COVID-19 and One-Lung Ventilation


title: Lack of transmission among healthcare workers in contact with a case of Middle East respiratory syndrome coronavirus infection in Thailand

text: INTRODUCTION: A hospital-associated outbreak of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was reported. We aimed to assess the effectiveness of infection control measures among healthcare workers (HCWs) who were exposed to a MERS patient and/or his body fluids in our institute. METHODS: A descriptive study was conducted among HCWs who worked with a MERS patient in Bamrasnaradura Infectious Diseases Institute, Thailand, between 18 June and 3 July 2015. Contacts were defined as HCWs who worked in the patient’s room or with the patient’s body fluids. Serum samples from all contacts were collected within 14 days of last contact and one month later. Paired sera were tested for detection of MERS‐CoV antibodies by using an indirect ELISA. RESULTS: Thirty-eight (88.4 %) of 43 identified contacts consented to enroll. The mean (SD) age was 38.1 (11.1) years, and 79 % were females. The median (IQR) cumulative duration of work of HCWs in the patient’s room was 35 (20–165) minutes. The median (IQR) cumulative duration of work of HCWs with the patient’s blood or body fluids in laboratory was 67.5 (43.7–117.5) minutes. All contacts reported 100 % compliance with hand hygiene, using N95 respirator, performing respirator fit test, wearing gown, gloves, eye protection, and cap during their entire working period. All serum specimens of contacts tested for MERS-CoV antibodies were negative. CONCLUSIONS: We provide evidence of effective infection control practices against MERS-CoV transmission in a healthcare facility. Strict infection control precautions can protect HCWs. The optimal infection control measures for MERS-CoV should be further evaluated.


title: Priorisierung von Pflegeheimbewohnern aus notfallmedizinischer Sicht: Corona-Pandemie 2020

text: Aus notfallmedizinischer Sicht sollten geriatrische Patienten in Pflege- und Seniorenheimen bereits vor einem „Massenanfall von infizierten Personen” eine Priorisierung auf der Basis des ACP(Advance Care Planning)-Konzepts erfahren.


title: Epidemiology and Phylogenetic Analysis of Viral Respiratory Infections in Vietnam

text: Acute respiratory infections (ARIs) impose a major public health burden on fragile healthcare systems of developing Southeast Asian countries such as Vietnam. The epidemiology, genetic diversity and transmission patterns of respiratory viral pathogens that circulate in this region are not well characterized. We used RT-PCR to screen for 14 common respiratory viruses in nasal/throat samples from 4326 ARI patients from 5 sites in Vietnam during 2012–2016. 64% of patients tested positive for viruses; 14% tested positive multiple co-infecting viruses. The most frequently detected viruses were Respiratory syncytial virus (RSV, 23%), Human Rhinovirus (HRV, 13%), Influenza A virus (IAV, 11%) and Human Bocavirus (HBoV, 7%). RSV infections peaked in July to October, were relatively more common in children <1 year and in the northernmost hospital. IAV infections peaked in December to February and were relatively more common in patients >5 years in the central region. Coinfection with IAV or RSV was associated with increased disease severity compared with patients only infected with HBoV or HRV. Over a hundred genomes belonging to 13 families and 24 genera were obtained via metagenomic sequencing, including novel viruses and viruses less commonly associated with ARIs. Phylogenetic and phylogeographic analyses further indicated that neighboring countries were the most likely source of many virus lineages causing ARIs in Vietnam and estimated the period that specific lineages have been circulating. Our study illustrates the value of applying the state-of-the-art virus diagnostic methods (multiplex RT-PCR and metagenomic sequencing) and phylodynamic analyses at a national level to generate an integrated picture of viral ARI epidemiology.


Anthropology: Anklebone kicks up primate debate


title: A case of mucolipidosis II presenting with prenatal skeletal dysplasia and severe secondary hyperparathyroidism at birth

text: Mucolipidosis II (ML II) or inclusion cell disease (I-cell disease) is a rarely occurring autosomal recessive lysosomal enzyme-targeting disease. This disease is usually found to occur in individuals aged between 6 and 12 months, with a clinical phenotype resembling that of Hurler syndrome and radiological findings resembling those of dysostosis multiplex. However, we encountered a rare case of an infant with ML II who presented with prenatal skeletal dysplasia and typical clinical features of severe secondary hyperparathyroidism at birth. A female infant was born at 37(+1) weeks of gestation with a birth weight of 1,690 g (<3rd percentile). Prenatal ultrasonographic findings revealed intrauterine growth retardation and skeletal dysplasia. At birth, the patient had characteristic features of ML II, and skeletal radiographs revealed dysostosis multiplex, similar to rickets. In addition, the patient had high levels of alkaline phosphatase and parathyroid hormone, consistent with severe secondary neonatal hyperparathyroidism. The activities of β-D-hexosaminidase and α-N-acetylglucosaminidase were moderately decreased in the leukocytes but were 5- to 10-fold higher in the plasma. Examination of a placental biopsy specimen showed foamy vacuolar changes in trophoblasts and syncytiotrophoblasts. The diagnosis of ML II was confirmed via GNPTAB genetic testing, which revealed compound heterozygosity of c.3091C>T (p.Arg1031X) and c.3456_3459dupCAAC (p.Ile1154GlnfsX3), the latter being a novel mutation. The infant was treated with vitamin D supplements but expired because of asphyxia at the age of 2 months.


title: Clinicopathological Phenotype of Autosomal Recessive Cholesterol Deficiency in Holstein Cattle

text: BACKGROUND: Cholesterol deficiency (CD), a newly identified autosomal recessive genetic defect in Holstein cattle, is associated with clinical signs of diarrhea, failure to thrive, and hypocholesterolemia. HYPOTHESIS/OBJECTIVES: The objective is to describe the clinicopathological phenotype of affected Holstein cattle homozygous for the causative apolipoprotein B gene (APOB) mutation. ANIMALS: Six Holstein cattle, 5 calves with a clinical history of chronic diarrhea, and 1 heifer with erosions in the buccal cavity and neurologic symptoms were admitted to the Clinic for Ruminants. METHODS: This case review included a full clinical examination, a complete blood count, blood chemistry, and measurements of cholesterol and triglycerides. The animals were euthanized and necropsied. A PCR‐based direct gene test was applied to determine the APOB genotype. RESULTS: All 6 animals were inbred, could be traced back to the sire Maughlin Storm, and were confirmed homozygous for the APOB mutation. The clinical phenotype included poor development, underweight, and intermittent diarrhea in the calves, and neurologic signs in the heifer included hypermetria and pacing. Hypocholesterolemia and low triglycerides concentrations were present in all animals. The pathological phenotype of all animals was steatorrhea with enterocytes of the small intestine containing intracytoplasmic lipid vacuoles. The peripheral nervous system of the heifer displayed degenerative changes. CONCLUSIONS AND CLINICAL IMPORTANCE: Suspicion of CD in Holstein cattle is based on the presence of chronic diarrhea with no evidence of primary infections. Confirmation of the associated APOB gene mutation is needed. Additionally, the heifer demonstrated primarily signs of neurologic disease providing an unexpected phenotype of CD.


title: Rotavirus I in feces of a cat with diarrhea

text: A divergent rotavirus I was detected using viral metagenomics in the feces of a cat with diarrhea. The eleven segments of rotavirus I strain Felis catus encoded non-structural and structural proteins with amino acid identities ranging from 25 to 79% to the only two currently sequenced members of that viral species both derived from canine feces. No other eukaryotic viral sequences nor bacterial and protozoan pathogens were detected in this fecal sample suggesting the involvement of rotavirus I in feline diarrhea. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11262-017-1440-4) contains supplementary material, which is available to authorized users.


title: New Metrics for Evaluating Viral Respiratory Pathogenesis

text: Viral pathogenesis studies in mice have relied on markers of severe systemic disease, rather than clinically relevant measures, to evaluate respiratory virus infection; thus confounding connections to human disease. Here, whole-body plethysmography was used to directly measure changes in pulmonary function during two respiratory viral infections. This methodology closely tracked with traditional pathogenesis metrics, distinguished both virus- and dose-specific responses, and identified long-term respiratory changes following both SARS-CoV and Influenza A Virus infection. Together, the work highlights the utility of examining respiratory function following infection in order to fully understand viral pathogenesis.


title: Diagnostic accuracy of two point‐of‐care kits for the diagnosis of Giardia species infection in dogs

text: OBJECTIVES: The objective of this study was to compare results obtained by ZnSO(4) Flotation and SNAP (®)Giardia to those generated by the new point‐of‐care tests Single and Triple Rapid. METHODS: Prospective study evaluating 51 canine faecal samples submitted at a reference laboratory for the presence of Giardia spp. Kappa statistics, specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) were calculated by comparing the new tests to the combined results of ZnSO(4) and SNAP tests. RESULTS: There was fair (Single Rapid, j=0·434) to good (Triple Rapid, j =0·797) agreement with the reference tests. At this study's prevalence (59 to 61%), specificities and PPV were high (1·00) with both Rapid tests, but sensitivities and NPV were lower for the Single than for the Triple (0·48 vs 0·83 and 0·55 vs 0·80) tests. At lower prevalence rates, both tests exhibited a high PPV (1·00), but the NPV were higher with the Triple (0·96 to 0·99) than the Single (0·88 to 0·96) Rapid test. CLINICAL SIGNIFICANCE: Both tests exhibited excellent PPV values at all prevalence rates but an excellent NPV only at low prevalence. As the prevalence is likely to be low (<15%) in clinical settings, we propose that these tests may be helpful in the in‐house diagnosis of Giardia spp infection. However, they exhibit lower sensitivity than the combined sensitivity of ZnSO(4) and SNAP tests, particularly in high prevalence settings.


title: Hospital Preparation for Severe Acute Respiratory Syndrome Using a Multidisciplinary Task Force

text: Abstract BACKGROUND: In March 2003, the severe acute respiratory syndrome (SARS) epidemic was recognized in China. The disease quickly spread to countries around the world and was transmitted in healthcare settings. Infection control professionals had to formulate a response to potential cases of SARS presenting to healthcare facilities. OBJECTIVE: To formulate and operationalize a plan for education and training of staff and to ensure availability of personal protective equipment (PPE) and adherence to infection control protocols to prevent SARS transmission in a large urban healthcare institution. METHODS: A multidisciplinary task force was charged with maintaining up-to-date knowledge about the SARS epidemic and providing education and training to staff in the hospital and outlying clinics. Signage for SARS triage and SARS isolation was created. Policies and checklists were developed for designated patient areas, and SARS carts and boxes stocked with PPE were obtained for these areas. A new “observer” role was created to ensure adherence to isolation procedures when caring for SARS patients. An educational video was made for distribution to healthcare workers. RESULTS: The SARS task force developed a cohesive package of policies, procedures, signage, and patient education in multiple languages. We developed a system to supply PPE and education to staff who might care for SARS patients. A new video will make staff education more accessible, especially for those working off-site or during nontraditional hours. CONCLUSION: The SARS task force responded to an emerging infectious threat and is a model for continued response to potential biological emergencies.


title: Scientific Opinion on porcine epidemic diarrhoea and emerging porcine deltacoronavirus

text: In the last decade, many porcine epidemic diarrhoea (PED) outbreaks have been reported by several countries in Asia whereas only a few Member States of the European Union (EU) have reported PED clinical cases and/or PED virus (PEDV)‐seropositive animals. This alphacoronavirus was first reported in the USA in May 2013, followed by rapid spread throughout the country and outbreaks reported by several countries in the Americas. The recent PEDV‐EU isolates have high level of sequence identity to PEDV‐Am isolates. Based on nucleotide sequencing, multiple variants of PEDV are circulating in Europe, the Americas and Asia but any difference in virulence and antigenicity is currently unknown. Serological cross‐reactivity has been reported between PEDV isolated in Europe and in the Americas; however no data regarding cross‐protection are available. The impact of different PEDV strains is difficult to compare between one country and another, since impact is dependent not only on pathogenicity but also on factors such as biosecurity, farm management, sanitary status or herd immune status. However, the clinical signs of PEDV infections in naive pigs are similar in different countries with mortalities up to 100% in naive newborn piglets. The impact of recently reported PED outbreaks in Asia and the USA seems to be more severe than what has been described in Europe. Infected animals, faeces, feed and objects contaminated with faeces are matrices that have been reported to transmit PEDV between farms. Infectious PEDV has been detected in spray‐dried porcine plasma (SDPP) in one study but the origin of the infectious PEDV in SDPP is not clear. Detection of porcine deltacoronavirus (PDCoV) has been reported in a few countries but only limited testing has been done. Based on the currently available information, it seems that PDCoV would have a lower impact than PEDV.


title: Suppression of Coronavirus Replication by Cyclophilin Inhibitors

text: Coronaviruses infect a variety of mammalian and avian species and cause serious diseases in humans, cats, mice, and birds in the form of severe acute respiratory syndrome (SARS), feline infectious peritonitis (FIP), mouse hepatitis, and avian infectious bronchitis, respectively. No effective vaccine or treatment has been developed for SARS-coronavirus or FIP virus, both of which cause lethal diseases. It has been reported that a cyclophilin inhibitor, cyclosporin A (CsA), could inhibit the replication of coronaviruses. CsA is a well-known immunosuppressive drug that binds to cellular cyclophilins to inhibit calcineurin, a calcium-calmodulin-activated serine/threonine-specific phosphatase. The inhibition of calcineurin blocks the translocation of nuclear factor of activated T cells from the cytosol into the nucleus, thus preventing the transcription of genes encoding cytokines such as interleukin-2. Cyclophilins are peptidyl-prolyl isomerases with physiological functions that have been described for many years to include chaperone and foldase activities. Also, many viruses require cyclophilins for replication; these include human immunodeficiency virus, vesicular stomatitis virus, and hepatitis C virus. However, the molecular mechanisms leading to the suppression of viral replication differ for different viruses. This review describes the suppressive effects of CsA on coronavirus replication.


title: Sex Differences in Mortality from COVID-19 Pandemic: Are Men Vulnerable and Women Protected?

text: Abstract Sex disaggregated data is an important for reducing health inequities in medicine. Global data suggests that is a sex difference in mortality from COVID-19. In this report, we explore plausible reasons for this sex difference including the contribution of underlying cardiovascular risk factors, high risk behaviors, immune response and biological differences between men and women.


title: Bench-to-bedside review: Rare and common viral infections in the intensive care unit – linking pathophysiology to clinical presentation

text: Viral infections are common causes of respiratory tract disease in the outpatient setting but much less common in the intensive care unit. However, a finite number of viral agents cause respiratory tract disease in the intensive care unit. Some viruses, such as influenza, respiratory syncytial virus (RSV), cytomegalovirus (CMV), and varicella-zoster virus (VZV), are relatively common. Others, such as adenovirus, severe acute respiratory syndrome (SARS)-coronavirus, Hantavirus, and the viral hemorrhagic fevers (VHFs), are rare but have an immense public health impact. Recognizing these viral etiologies becomes paramount in treatment, infection control, and public health measures. Therefore, a basic understanding of the pathogenesis of viral entry, replication, and host response is important for clinical diagnosis and initiating therapeutic options. This review discusses the basic pathophysiology leading to clinical presentations in a few common and rare, but important, viruses found in the intensive care unit: influenza, RSV, SARS, VZV, adenovirus, CMV, VHF, and Hantavirus.


docid: unnrflmr

title: Broad-spectrum coronavirus antiviral drug discovery

text: Introduction: The highly pathogenic coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are lethal zoonotic viruses that have emerged into human populations these past 15 years. These coronaviruses are associated with novel respiratory syndromes that spread from person-to-person via close contact, resulting in high morbidity and mortality caused by the progression to Acute Respiratory Distress Syndrome (ARDS). Areas covered: The risks of re-emergence of SARS-CoV from bat reservoir hosts, the persistence of MERS-CoV circulation, and the potential for future emergence of novel coronaviruses indicate antiviral drug discovery will require activity against multiple coronaviruses. In this review, approaches that antagonize viral nonstructural proteins, neutralize structural proteins, or modulate essential host elements of viral infection with varying levels of efficacy in models of highly pathogenic coronavirus disease are discussed. Expert opinion: Treatment of SARS and MERS in outbreak settings has focused on therapeutics with general antiviral activity and good safety profiles rather than efficacy data provided by cellular, rodent, or nonhuman primate models of highly pathogenic coronavirus infection. Based on lessons learned from SARS and MERS outbreaks, lack of drugs capable of pan-coronavirus antiviral activity increases the vulnerability of public health systems to a highly pathogenic coronavirus pandemic.


A Cured COVID-19 case of 86-year-old with 13 chronic diseases: A Case Report


title: Role of Glutathionylation in Infection and Inflammation

text: Glutathionylation, that is, the formation of mixed disulfides between protein cysteines and glutathione (GSH) cysteines, is a reversible post-translational modification catalyzed by different cellular oxidoreductases, by which the redox state of the cell modulates protein function. So far, most studies on the identification of glutathionylated proteins have focused on cellular proteins, including proteins involved in host response to infection, but there is a growing number of reports showing that microbial proteins also undergo glutathionylation, with modification of their characteristics and functions. In the present review, we highlight the signaling role of GSH through glutathionylation, particularly focusing on microbial (viral and bacterial) glutathionylated proteins (GSSPs) and host GSSPs involved in the immune/inflammatory response to infection; moreover, we discuss the biological role of the process in microbial infections and related host responses.


title: Environmental Health and Bioterrorism☆

text: Abstract Environment has complex and permanent relations with the biological warfare in comparison to other war types (conventional, nuclear, chemical). Changes of the environment interfere with many of the major determinants of biological warfare. The most probable type and the key issue of biological war is bioterrorism. Bioterrorism is defined as a release of biological agents or toxins that affect human beings, animals, or plants with the intent to harm or intimidate. The essence of bioterrorism is a biological attack. Four components are required for a biological attack: perpetrators, agents, mediums/means of delivery, and targets.


Colonization and infection of the respiratory tract: What do we know?


title: Development and optimization of plaque assays for rat coronaviruses

text: Abstract Plaque assays under Sephadex or agarose overlays are described for rat coronaviruses (RCVs) grown in L2 mouse fibroblasts. A plaque assay using Sephadex was simple; however, viable plaques could not be collected for propagation, and fixation was necessary before evaluation. Plaque formation under agarose was optimized using diethylaminoethyl-dextran (DEAE-D) in the pre-treatment and absorption media and trypsin added to the absorption media and agarose overlay. The use of DEAE-D alone, trypsin alone or trypsin combined with DEAE-D significantly increased plaque numbers and visibility. Plaque numbers were highest when pre-treatment media contained DEAE-D, absorption media contained DEAE-D and trypsin, and the agarose overlay contained trypsin. The assay was useful for plaque isolation and quantification of sialodacryoadenitis virus (SDA), Parker's rat coronavirus (PRCV) and other coronavirus isolates from rats and its specificity was demonstrated by plaque-reduction neutralization testing. These methods will facilitate production of cloned virus stocks for study of RCV biology and virus quantification for in vitro and in vivo studies of RCVs.


title: SARS-CoV nucleocapsid protein interacts with cellular pyruvate kinase protein and inhibits its activity

text: The pathogenesis of SARS-CoV remains largely unknown. To study the function of the SARS-CoV nucleocapsid protein, we have conducted a yeast two-hybrid screening experiment to identify cellular proteins that may interact with the SARS-CoV nucleocapsid protein. Pyruvate kinase (liver) was found to interact with SARS-CoV nucleocapsid protein in this experiment. The binding domains of these two proteins were also determined using the yeast two-hybrid system. The physical interaction between the SARS-CoV nucleocapsid and cellular pyruvate kinase (liver) proteins was further confirmed by GST pull-down assay, co-immunoprecipitation assay and confocal microscopy. Cellular pyruvate kinase activity in hepatoma cells was repressed by SARS-CoV nucleocapsid protein in either transiently transfected or stably transfected cells. PK deficiency in red blood cells is known to result in human hereditary non-spherocytic hemolytic anemia. It is reasonable to assume that an inhibition of PKL activity due to interaction with SARS-CoV N protein is likely to cause the death of the hepatocytes, which results in the elevation of serum alanine aminotransferase and liver dysfunction noted in most SARS patients. Thus, our results suggest that SARS-CoV could reduce pyruvate kinase activity via its nucleocapsid protein, and this may in turn cause disease.


Análisis de las coinfecciones detectadas entre los virus gripales A y B y otros virus respiratorios, 2012-2013


title: Broad Host Range of SARS-CoV-2 Predicted by Comparative and Structural Analysis of ACE2 in Vertebrates

text: The novel coronavirus SARS-CoV-2 is the cause of Coronavirus Disease-2019 (COVID-19). The main receptor of SARS-CoV-2, angiotensin I converting enzyme 2 (ACE2), is now undergoing extensive scrutiny to understand the routes of transmission and sensitivity in different species. Here, we utilized a unique dataset of 410 vertebrates, including 252 mammals, to study cross-species conservation of ACE2 and its likelihood to function as a SARS-CoV-2 receptor. We designed a five-category ranking score based on the conservation properties of 25 amino acids important for the binding between receptor and virus, classifying all species from very high to very low. Only mammals fell into the medium to very high categories, and only catarrhine primates in the very high category, suggesting that they are at high risk for SARS-CoV-2 infection. We employed a protein structural analysis to qualitatively assess whether amino acid changes at variable residues would be likely to disrupt ACE2/SARS-CoV-2 binding, and found the number of predicted unfavorable changes significantly correlated with the binding score. Extending this analysis to human population data, we found only rare (<0.1%) variants in 10/25 binding sites. In addition, we observed evidence of positive selection in ACE2 in multiple species, including bats. Utilized appropriately, our results may lead to the identification of intermediate host species for SARS-CoV-2, justify the selection of animal models of COVID-19, and assist the conservation of animals both in native habitats and in human care.


title: Enablers of, and barriers to, optimal glove and mask use for routine care in the emergency department: an ethnographic study of Australian clinicians

text: Abstract Background The risk of healthcare-acquired infection increases during outbreaks of novel infectious diseases. Emergency department (ED) clinicians are at high risk of exposure to both these and common communicable diseases. Personal protective equipment (PPE) is recommended to protect clinicians from acquiring, or becoming vectors of, infection, yet compliance is typically sub-optimal. Little is known about factors that influence use of PPE—specifically gloves and masks—during routine care in the ED. Methods This was an ethnographic study, incorporating documentation review, field observations and interviews. The theoretical domains framework (TDF) was used to aid thematic analysis and identify relevant enablers of and barriers to optimal PPE use. Results Thirty-one behavioural themes were identified that influenced participants’ use of masks and gloves. There were significant differences, namely: more reported enablers of glove use vs more barriers to mask use. Reasons included more positive unit culture towards glove use, and lower perception of risk via facial contamination. Conclusion Emerging infectious diseases, spread (among other routes) by respiratory droplets, have caused global outbreaks. Emergency clinicians should ensure that, as with gloves, the use of masks is incorporated into routine cares where appropriate. Further research which examines items of PPE independently is warranted.


title: Clinical analysis of pregnant women with 2019 novel coronavirus pneumonia

text: The aim is to evaluate pregnant women infected with coronavirus disease 2019 (COVID‐19) and provide help for clinical prevention and treatment. All five cases of pregnant women confirmed COVID‐19 were collected among patients who admitted to the Maternal and Child Hospital of Hubei Province between January 20 and February 10, 2020. All patients, aging from 25 to 31 years old, had the gestational week from 38th weeks to 41st weeks. All pregnant women did not have an antepartum fever but developed a low‐grade fever (37.5℃‐38.5℃) within 24 hours after delivery. All patients had normal liver and renal function, two patients had elevated plasma levels of the myocardial enzyme. Unusual chest imaging manifestations, featured with ground‐grass opacity, were frequently observed in bilateral (three cases) or unilateral lobe (two cases) by computed tomography (CT) scan. All labors smoothly processed, the Apgar scores were 10 points 1 and 5 minutes after delivery, no complications were observed in the newborn. Pregnancy and perinatal outcomes of patients with COVID‐19 should receive more attention. It is probable that pregnant women diagnosed with COVID‐19 have no fever before delivery. Their primary initial manifestations were merely low‐grade postpartum fever or mild respiratory symptoms. Therefore, the protective measures are necessary on admission; the instant CT scan and real‐time reverse‐transcriptase polymerase‐chain‐reaction assay should be helpful in early diagnosis and avoid cross‐infection on the occasion that patients have fever and other respiratory signs.


title: Alternative Care Sites: An Option in Disasters

text: During the current COVID-19 pandemic, the limited surge capacity of the healthcare system is being quickly overwhelmed. Similar scenarios play out when an institution’s systems fail, or when local or regional disasters occur. In these situations, it becomes necessary to use one or more alternative care sites (ACS). Situated in a variety of non-healthcare structures, ACS may be used for ambulatory, acute, subacute, or chronic care. Developing alternative care facilities is the disaster-planning step that moves communities from talking to doing. This commitment pays real dividends if a disaster of any magnitude strikes. This paper discusses the basic criteria for selecting, establishing and ultimately closing an ACS, difficulties of administration, staffing, security, and providing basic supplies and equipment.


title: Ancient recombination events and the origins of hepatitis E virus

text: BACKGROUND: Hepatitis E virus (HEV) is an enteric, single-stranded, positive sense RNA virus and a significant etiological agent of hepatitis, causing sporadic infections and outbreaks globally. Tracing the evolutionary ancestry of HEV has proved difficult since its identification in 1992, it has been reclassified several times, and confusion remains surrounding its origins and ancestry. RESULTS: To reveal close protein relatives of the Hepeviridae family, similarity searching of the GenBank database was carried out using a complete Orthohepevirus A, HEV genotype I (GI) ORF1 protein sequence and individual proteins. The closest non-Hepeviridae homologues to the HEV ORF1 encoded polyprotein were found to be those from the lepidopteran-infecting Alphatetraviridae family members. A consistent relationship to this was found using a phylogenetic approach; the Hepeviridae RdRp clustered with those of the Alphatetraviridae and Benyviridae families. This puts the Hepeviridae ORF1 region within the “Alpha-like” super-group of viruses. In marked contrast, the HEV GI capsid was found to be most closely related to the chicken astrovirus capsid, with phylogenetic trees clustering the Hepeviridae capsid together with those from the Astroviridae family, and surprisingly within the “Picorna-like” supergroup. These results indicate an ancient recombination event has occurred at the junction of the non-structural and structure encoding regions, which led to the emergence of the entire Hepeviridae family. The Astroviridae capsid is also closely related to the Tymoviridae family of monopartite, T = 3 icosahedral plant viruses, whilst its non-structural region is related to viruses of the Potyviridae; a large family of plant-infecting viruses with a flexible filamentous rod-shaped virion. Thus, we identified a separate inter-viral family recombination event, again at the non-structural/structural junction, which likely led to the creation of the Astroviridae. CONCLUSIONS: In summary, we have shown that new viral families have been created though recombination at the junction of the genome that encodes non-structural and structural proteins, and such recombination events are implicated in the genesis of important human pathogens; HEV, astrovirus and rubella virus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12862-016-0785-y) contains supplementary material, which is available to authorized users.


title: COVID-19: Role of neutrophil extracellular traps in acute lung injury

text: Abstract The COVID-19 pandemic has caused significant disease and loss of life worldwide. SARS-CoV-2 causes respiratory infection with pneumonia, acute respiratory distress syndrome (ARDS), coagulopathy, and multiorgan failure in a significant number of patients. The pathophysiology of this disease is still unknown. Neutrophil extracellular traps (NETs) are mesh-like structures composed of DNA and covered with histones and proteinaceous enzymes released by neutrophils during a specialized type of cell death called “NETosis.” The primary function of NETs is to trap and kill microbes; however, dysregulation of neutrophils with excessive production of NETs can culminate in disease. Interestingly, higher levels of NETs have been observed in the serum samples of COVID-19 patients, which is correlated with the severity of this disease. This paper describes the role of excessive NET release in acute lung injury, as seen in COVID-19 patients.


title: Tracking Nosocomial Diseases at Individual Level with a Real-Time Indoor Positioning System

text: Our research is motivated by the rapidly-evolving outbreaks of rare and fatal infectious diseases, for example, the severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome. In many of these outbreaks, main transmission routes were healthcare facility-associated and through person-to-person contact. While a majority of existing work on modelling of the spread of infectious diseases focuses on transmission processes at a community level, we propose a new methodology to model the outbreaks of healthcare-associated infections (HAIs), which must be considered at an individual level. Our work also contributes to a novel aspect of integrating real-time positioning technologies into the tracking and modelling framework for effective HAI outbreak control and prompt responses. Our proposed solution methodology is developed based on three key components – time-varying contact network construction, individual-level transmission tracking and HAI parameter estimation – and aims to identify the hidden health state of each patient and worker within the healthcare facility. We conduct experiments with a four-month human tracking data set collected in a hospital, which bore a big nosocomial outbreak of the 2003 SARS in Hong Kong. The evaluation results demonstrate that our framework outperforms existing epidemic models for characterizing macro-level phenomena such as the number of infected people and epidemic threshold.


title: Reorienting entrepreneurial support infrastructure to tackle a social crisis: A rapid response

text: Abstract Chile is experiencing its worst economic and social crisis in decades, which is adversely impacting entrepreneurs and SMEs. Chile’s Economic Development Agency is seeking to support recovery efforts by reorienting its entrepreneurship programs and ecosystem support capacity. What makes the reorientation especially challenging is the need to ensure all actions are sensitive to the causes of the social unrest, where arguably extant entrepreneurship policy has played a role. Theory and evidence in entrepreneurship literature seem insufficient to inform immediate actions. In this rapid response paper, we leverage and translate research on ecosystem democracy, spontaneous venturing and entrepreneurship-enabled social cohesion to inform decision-making and contribute to the development of policy solutions. We propose an entrepreneurship policy reorientation model, including interventions during and post crisis, potentially capable of minimizing the effects of the crisis and changing the orientation of future support.


docid: pjotppso

title: Vitamin intervention for cytokine storm in the patients with coronavirus disease 2019


title: Origin time and epidemic dynamics of the 2019 novel coronavirus

text: The 2019 novel coronavirus (2019-nCoV) have emerged from Wuhan, China. Studying the epidemic dynamics is crucial for further surveillance and control of the outbreak. We employed a Bayesian framework to infer the time-calibrated phylogeny and the epidemic dynamics represented by the effective reproductive number (Re) changing over time from the genomic sequences available from GISAID. The origin time is estimated to be December 17, 2019 (95% CI: December 5, 2019 – December 23, 2019). The median estimate of Re ranges from 0.2 to 2.2 and changes drastically over time. This study provides an early insight of the 2019-nCoV epidemic.


title: COVID-19 prevalence and fatality rates in association with air pollution emission concentrations and emission sources()

text: The novel coronavirus disease (COVID-19) is primarily respiratory in nature, and as such, there is interest in examining whether air pollution might contribute to disease susceptibility or outcome. We merged data on COVID-19 cumulative prevalence and fatality rates as of May 31, 2020 with 2014–2019 pollution data from the US Environmental Protection Agency Environmental Justice Screen (EJSCREEN), with control for state testing rates, population density, and population covariate data from the County Health Rankings. Pollution data included three types of air emission concentrations (particulate matter<2.5 μm (PM2.5), ozone and diesel particulate matter (DPM)), and four pollution source variables (proximity to traffic, National Priority List sites, Risk Management Plan (RMP) sites, and hazardous waste treatment, storage and disposal facilities (TSDFs)). Results of mixed model linear multiple regression analyses indicated that, controlling for covariates, COVID-19 prevalence and fatality rates were significantly associated with greater DPM. Proximity to TSDFs was associated to greater fatality rates, and proximity to RMPs was associated with greater prevalence rates. Results are consistent with previous research indicating that air pollution increases susceptibility to respiratory viral pathogens. Results should be interpreted cautiously given the ecological design, the time lag between exposure and outcome, and the uncertainties in measuring COVID-19 prevalence. Areas with worse prior air quality, especially higher concentrations of diesel exhaust, may be at greater COVID-19 risk, although further studies are needed to confirm these relationships.


title: The Fate of Mengovirus on Fiberglass Filter of Air Handling Units

text: One of the most important topics that occupy public health problems is the air quality. That is the reason why mechanical ventilation and air handling units (AHU) were imposed by the different governments in the collective or individual buildings. Many buildings create an artificial climate using heating, ventilation, and air-conditioning systems. Among the existing aerosols in the indoor air, we can distinguish the bioaerosol with biological nature such as bacteria, viruses, and fungi. Respiratory viral infections are a major public health issue because they are usually highly infective. We spend about 90% of our time in closed environments such as homes, workplaces, or transport. Some studies have shown that AHU contribute to the spread and transport of viral particles within buildings. The aim of this work is to study the characterization of viral bioaerosols in indoor environments and to understand the fate of mengovirus eukaryote RNA virus on glass fiber filter F7 used in AHU. In this study, a set-up close to reality of AHU system was used. The mengovirus aerosolized was characterized and measured with the electrical low pressure impact and the scanner mobility particle size and detected with RT-qPCR. The results about quantification and the level of infectivity of mengovirus on the filter and in the biosampler showed that mengovirus can pass through the filter and remain infectious upstream and downstream the system. Regarding the virus infectivity on the filter under a constant air flow, mengovirus was remained infectious during 10 h after aerosolization.


title: Sargramostim to treat patients with acute hypoxic respiratory failure due to COVID-19 (SARPAC): A structured summary of a study protocol for a randomised controlled trial

text: OBJECTIVES: The hypothesis of the proposed intervention is that Granulocyte-macrophage colony-stimulating factor (GM-CSF) has profound effects on antiviral immunity, and can provide the stimulus to restore immune homeostasis in the lung with acute lung injury post COVID-19, and can promote lung repair mechanisms, that lead to a 25% improvement in lung oxygenation parameters. Sargramostim is a man-made form of the naturally-occurring protein GM-CSF. TRIAL DESIGN: A phase 4 academic, prospective, 2 arm (1:1 ratio), randomized, open-label, controlled trial. PARTICIPANTS: Patients aged 18-80 years admitted to specialized COVID-19 wards in 5 Belgian hospitals with recent (< 2 weeks prior to randomization) confirmed COVID-19 infection and acute respiratory failure defined as a PaO2/FiO2 below 350 mmHg or SpO2 below 93% on minimal 2 L/min supplemental oxygen. Patients were excluded from the trial in case of (1) known serious allergic reactions to yeast-derived products, (2) lithium carbonate therapy, (3) mechanical ventilation prior to randomization, (4) peripheral white blood cell count above 25.000/μL and/or active myeloid malignancy, (5) high dose systemic steroid therapy (> 20 mg methylprednisolone or equivalent), (6) enrolment in another investigational study, (7) pregnant or breastfeeding or (8) ferritin levels > 2000 μg/mL. INTERVENTION AND COMPARATOR: Inhaled sargramostim 125 μg twice daily for 5 days in addition to standard care. Upon progression of disease requiring mechanical ventilation or to acute respiratory distress syndrome (ARDS) and initiation of mechanical ventilator support within the 5 day period, inhaled sargramostim will be replaced by intravenous sargramostim 125 μg/m(2) body surface area once daily until the 5 day period is reached. From day 6 onwards, progressive patients in the active group will have the option to receive an additional 5 days of IV sargramostim, based on the treating physician's assessment. Intervention will be compared to standard of care. Subjects progressing to ARDS and requiring invasive mechanical ventilatory support, from day 6 onwards in the standard of care group will have the option (clinician's decision) to initiate IV sargramostim 125m μg/m(2) body surface area once daily for 5 days. MAIN OUTCOMES: The primary endpoint of this intervention is measuring oxygenation after 5 days of inhaled (and intravenous) treatment through assessment of a change in pretreatment and post-treatment ratio of PaO2/FiO2 and through measurement of the P(A-a)O2 gradient (PAO2= Partial alveolar pressure of oxygen, PaO2=Partial arterial pressure of oxygen; FiO2= Fraction of inspired oxygen). RANDOMISATION: Patients will be randomized in a 1:1 ratio. Randomization will be done using REDCap (electronic IWRS system). BLINDING (MASKING): In this open-label trial neither participants, caregivers, nor those assessing the outcomes will be blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 80 patients with confirmed COVID-19 and acute hypoxic respiratory failure will be enrolled, 40 in the active and 40 in the control group. TRIAL STATUS: SARPAC protocol Version 2.0 (April 15 2020). Participant recruitment is ongoing in 5 Belgian Hospitals (i.e. University Hospital Ghent, AZ Sint-Jan Bruges, AZ Delta Roeselare, University Hospital Brussels and ZNA Middelheim Antwerp). Participant recruitment started on March 26(th) 2020. Given the current decline of the COVID-19 pandemic in Belgium, it is difficult to anticipate the rate of participant recruitment. TRIAL REGISTRATION: The trial was registered on Clinical Trials.gov on March 30(th), 2020 (ClinicalTrials.gov Identifier: NCT04326920) - retrospectively registered; https://clinicaltrials.gov/ct2/show/NCT04326920?term=sarpac&recrs=ab&draw=2&rank=1 and on EudraCT on March 24th, 2020 (Identifier: 2020-001254-22). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


docid: biundkbv

title: Protests in Hong Kong (2019–2020): a Perspective Based on Quality of Life and Well-Being

text: Triggered by the Fugitive Offenders and Mutual Legal Assistance in Criminal Matters Legislation (Amendment) Bill 2019 in Hong Kong (Extradition Bill), many protests have taken place in Hong Kong in 2019–2020. Using a perspective based on quality of life and well-being in different ecological systems, it is argued that the process of introducing the Bill is the “heat” which has ignited the “fuels” represented by 12 pre-existing and new issues in quality of life and well-being. These issues included distrust in the Central Government, lack of national identity, political dissatisfaction, economic strains, mental health threats, drop in family quality of life, lack of life skills education, lack of evidence-based national education in the formal curriculum, slow response of the Government, and alleged excessive use of force by the police. The fire has been intensified by “four strong winds”, including disinformation and misinformation, anonymity of the protesters, public support for the students, and support given by parties outside Hong Kong. Possible solutions in terms of promotion of quality of life and well-being with reference to the fire triangle are discussed.


docid: felcsozk

title: Antiviral and antiretroviral use in pregnancy

text: The history of antiviral and antiretroviral therapy is recent compared with many other medical therapies, including traditional antibiotics in pregnancy. There are few long-term data on which to base decisions of management in pregnancy. Accessing up-to-date information is critical to optimizing the safety of care for mothers and their infants. Exposure to medications in pregnancy can be toxic to a fetus in a gestational age-dependent manner. Determination of safe medications for pregnancy must take into consideration the need for certain medications and the possibility of inadvertent exposure in early pregnancy because of unplanned pregnancies. This article reviews the most commonly used antiviral and antiretroviral agents and places emphasis on the issues regarding use in pregnancy.


title: Invisibility and the extractive-pandemic nexus

text: • Covid-19 is reshaping the world economy. • Visibility of mining issues and social impacts is limited by the remote nature of extraction. • The pandemic is providing a platform for unchecked corporate self-ascriptions of virtue. • Regulatory control through public scrutiny has been suspended. • In this environment, scholars play a critical role in capturing the local conditions of both fast and ‘slow moving crises’.


title: A Digital Protein Microarray for COVID-19 Cytokine Storm Monitoring

text: Despite widespread concern for cytokine storms leading to severe morbidity in COVID-19, rapid cytokine assays are not routinely available for monitoring critically ill patients. We report the clinical application of a machine learning-based digital protein microarray platform for rapid multiplex quantification of cytokines from critically ill COVID-19 patients admitted to the intensive care unit (ICU) at the University of Michigan Hospital. The platform comprises two low-cost modules: (i) a semi-automated fluidic dispensing/mixing module that can be operated inside a biosafety cabinet to minimize the exposure of technician to the virus infection and (ii) a 12-12-15 inch compact fluorescence optical scanner for the potential near-bedside readout. The platform enabled daily cytokine analysis in clinical practice with high sensitivity (<0.4pg/mL), inter-assay repeatability (~10% CV), and near-real-time operation with a 10 min assay incubation. A cytokine profiling test with the platform allowed us to observe clear interleukin-6 (IL-6) elevations after receiving tocilizumab (IL-6 inhibitor) while significant cytokine profile variability exists across all critically ill COVID-19 patients and to discover a weak correlation between IL-6 to clinical biomarkers, such as Ferritin and CRP. Our data revealed large subject-to-subject variability in a patient's response to anti-inflammatory treatment for COVID-19, reaffirming the need for a personalized strategy guided by rapid cytokine assays.


title: Mechanisms of Innate Immune Evasion In Re-Emerging RNA Viruses

text: Recent outbreaks of Ebola, West Nile, Chikungunya, Middle Eastern Respiratory and other emerging/re-emerging RNA viruses continue to highlight the need to further understand the virus-host interactions that govern disease severity and infection outcome. As part of the early host antiviral defense, the innate immune system mediates pathogen recognition and initiation of potent antiviral programs that serve to limit virus replication and spread and activate adaptive immune responses. Concordantly, viral pathogens have evolved several strategies to counteract pathogen recognition and cell-intrinsic antiviral responses. In this Review, we highlight the major mechanisms of innate immune evasion by emerging and re-emerging RNA viruses, focusing on pathogens that pose significant risk to public health.


title: How COVID-19’s Disruption of the U.S. Correctional System Provides an Opportunity for Decarceration

text: The COVID-19 pandemic has amplified decades of vulnerabilities, disparities, and injustices within the U.S. correctional system. The spread of the coronavirus poses a particularly serious threat to those that comprise the system, including personnel, attorneys, prisoners, their families and extends into the communities in which facilities are located. These correctional facilities and communities were especially underprepared for the sudden onset of a highly contagious virus, which has resulted in an exceedingly high number of infections among those who work and are held in the facilities. Rampant overcrowding in the U.S. correctional system, an aging population, and a population exhibiting high rates of underlying health conditions are highly likely to exacerbate the spread of this highly contagious virus. This potentially dire set of interrelated circumstances necessitates rapid decarceration measures that effectively balance public safety and public health. Unfortunately, there has been unclear guidance as well as changing and even contradictory information coming from the federal government concerning rapid measures to mitigate the spread of infection to justice system personnel and federal prisoners. In this paper we summarize the federal response and how it has impacted those responsible for implementation. Furthermore, we discuss how systemic deleterious conditions of the U.S. correctional system serve as both accelerants to as well as effects of the pandemic. We end highlighting critical issues relating to early release due to COVID-19 that will necessitate future research.


title: Multifunctional roles of leader protein of foot-and-mouth disease viruses in suppressing host antiviral responses

text: Foot-and-mouth disease virus (FMDV) leader protein (L(pro)) is a papain-like proteinase, which plays an important role in FMDV pathogenesis. L(pro) exists as two forms, Lab and Lb, due to translation being initiated from two different start codons separated by 84 nucleotides. L(pro) self-cleaves from the nascent viral polyprotein precursor as the first mature viral protein. In addition to its role as a viral proteinase, L(pro) also has the ability to antagonize host antiviral effects. To promote FMDV replication, L(pro) can suppress host antiviral responses by three different mechanisms: (1) cleavage of eukaryotic translation initiation factor 4 γ (eIF4G) to shut off host protein synthesis; (2) inhibition of host innate immune responses through restriction of interferon-α/β production; and (3) L(pro) can also act as a deubiquitinase and catalyze deubiquitination of innate immune signaling molecules. In the light of recent functional and biochemical findings regarding L(pro), this review introduces the basic properties of L(pro) and the mechanisms by which it antagonizes host antiviral responses.


docid: vvauwhko

title: Pig trade networks through live pig markets in Guangdong Province, China

text: This study used social network analysis to investigate the indirect contact network between counties through the movement of live pigs through four wholesale live pig markets in Guangdong Province, China. All 14,118 trade records for January and June 2016 were collected from the markets and the patterns of pig trade in these markets analysed. Maps were developed to show the movement pathways. Evaluating the network between source counties was the primary objective of this study. A 1‐mode network was developed. Characteristics of the trading network were explored, and the degree, betweenness and closeness were calculated for each source county. Models were developed to compare the impacts of different disease control strategies on the potential magnitude of an epidemic spreading through this network. The results show that pigs from 151 counties were delivered to the four wholesale live pig markets in January and/or June 2016. More batches (truckloads of pigs sourced from one or more piggeries) were traded in these markets in January (8,001) than in June 2016 (6,117). The pigs were predominantly sourced from counties inside Guangdong Province (90%), along with counties in Hunan, Guangxi, Jiangxi, Fujian and Henan provinces. The major source counties (46 in total) contributed 94% of the total batches during the two‐month study period. Pigs were sourced from piggeries located 10 to 1,417 km from the markets. The distribution of the nodes' degrees in both January and June indicates a free‐scale network property, and the network in January had a higher clustering coefficient (0.54 vs. 0.39) and a shorter average pathway length (1.91 vs. 2.06) than that in June. The most connected counties of the network were in the central, northern and western regions of Guangdong Province. Compared with randomly removing counties from the network, eliminating counties with higher betweenness, degree or closeness resulted in a greater reduction of the magnitude of a potential epidemic. The findings of this study can be used to inform targeted control interventions for disease spread through this live pig market trade network in south China.


title: Chapter 9 Viral Strategies to Subvert the Mammalian Translation Machinery

text: Abstract Viruses do not carry their own protein biosynthesis machinery and the translation of viral proteins therefore requires that the virus usurps the machinery of the host cell. To allow optimal translation of viral proteins at the expense of cellular proteins, virus families have evolved a variety of methods to repress the host translation machinery, while allowing effective viral protein synthesis. Many viruses use noncanonical mechanisms that permit translation of their own RNAs under these conditions. Viruses have also developed mechanisms to evade host innate immune responses that would repress translation under conditions of viral infection, in particular PKR activation in response to double-stranded RNA (dsRNA). Importantly, the study of viral translation mechanisms has enormously enhanced our understanding of many aspects of the cellular protein biosynthesis pathway and its components. A number of unusual mechanisms of translation initiation that were first discovered in viruses have since been observed in cellular mRNAs, and it has become apparent that a diverse range of translation mechanisms operates in eukaryotes, allowing subtle regulation of this essential process.


title: Active fractions of mannoproteins derived from yeast cell wall stimulate innate and acquired immunity of adult and elderly dogs

text: Abstract Nutritional intervention in older dogs aims to increase lifespan and improve life quality as well as delay the development of diseases related to ageing. It is believed that active fractions of mannoproteins (AFMs) obtained through extraction and fractionation of yeast cell walls (Saccharomyces cerevisiae) may beneficially modulate the immune system. However, studies that have evaluated this component and the effects of ageing on the immune system of dogs are scarce. This study aimed to evaluate the immunological effects of AFMs in adult and elderly dogs. Three extruded iso-nutrient experimental diets were formulated: without addition of AFM (T0); with AFM at 400 mg/kg (T400); and with AFM at 800 mg/kg (T800). Thirty-six beagle dogs were used, and six experimental treatments, resulting in combinations of age (adult and elderly) and diet (T0, T400, and T800), were evaluated. On days zero, 14, and 28, blood samples were obtained for leucocyte phenotyping and phagocytosis assays. On days zero and 28, a lymphoproliferation test, quantification of reactive oxygen (H2O2) and nitrogen (NO) intermediate production, evaluation of faecal immunoglobulin A (IgA) content, and a delayed cutaneous hypersensitivity test (DCHT) were performed. Statistical analyses were performed with SAS software. Repeated measure variance analyses were performed, and means were compared by the Tukey test. Values of P ≤ 0.05 were considered significant, and values of P ≤ 0.10 were considered tendencies. Dogs fed T400 tended to have higher neutrophilic phagocytic activity than dogs fed T800 (P = 0.073). Regarding reactive oxygen intermediates, bacterial lipopolysaccharide (LPS)-stimulated neutrophils from animals that were fed T400 had a tendency to produce more H2O2 than those from animals fed the control diet (P = 0.093). Elderly dogs, when compared to adult dogs, had lower absolute T and B lymphocyte counts, lower auxiliary T lymphocyte counts, and higher cytotoxic T lymphocyte counts (P < 0.05). A significant effect of diet, age, and time with saline inoculation was noted for the DCHT. There was no effect of diet or age on faecal IgA content in dogs. This study suggests beneficial effects of mannoproteins on the specific and nonspecific immune responses in adult and elderly dogs.


title: La batalla contra la enfermedad del Coronavirus 2019 (COVID-19): Manejo de Emergencia y Control de Infecciones en un Departamento de Radiología

text: Objetivo Describir las estrategias, manejo de emergencias y los procedimientos de control de infecciones de nuestro departamento durante el brote de la enfermedad por coronavirus 2019 (COVID-19). Métodos Creamos un equipo de manejo de emergencias. El equipo estableció varias medidas: Reconfiguración del flujo de trabajo en el departamento de radiología, distribución de material de protección personal y adiestramiento del personal, procedimientos para la obtención de imágenes en pacientes sospechosos o confirmados con COVID-19, así como para pacientes sin historial de exposición o síntomas. Aquellos con sospecha o confirmación de COVID-19 fueron escaneados en una unidad dedicada para ello. Result ados: Del 21 de enero del 2020 hasta el 9 de marzo del 2020, 3,083 personas con sospecha o confirmación de COVID-19 recibieron CT de torax. Incluyendo los exámenes iniciales y repetidos, el número total de CT fue 3,340. Como resultado de nuestras medidas de precaución, ninguno de los miembros del personal del departamento de radiología fue infectado con COVID-19. Conclusión Las estrategias de planificación y las protecciones adecuadas pueden ayudar a proteger a los pacientes y al personal contra una enfermedad altamente infecciosa. Y a la misma vez ayudar a mantener la capacidad de atender un volumen alto de pacientes.


title: Viral infections in patients with acute respiratory infection in Northwest of Iran

text: INTRODUCTION: Acute respiratory infection (ARI) is one of the main causes of morbidity and mortality all around the world. The aim of this study was to determine the frequency, mortality and association with clinical entities of influenza virus type A, influenza virus type B, respiratory syncytial virus (RSV), coronavirus, and adenoviruses in patients with ARI. MATERIALS AND METHODS: During September 2014 till May 2015, 143 respiratory inpatients samples for viral testing collected from central Hospital in Northwest of Iran. A real-time reverse transcription-PCR (RT-PCR) assay was done to allow in one test the detection of influenza A and B viruses. Also, RSV and adenovirus were identified by Immunochromatography test. RESULTS: Twenty-four (46%) cases were positive for influenza A, which 11 (46%) of them were subtype H1N1 and 13 (54%) cases were subtype H3N2. Also, 21 (40%) cases were positive for influenza B, 5 (10%) cases were positive for RSV, and 2 (4%) cases were positive for adenovirus. One of the patients was positive for both influenza A and adenovirus. Two of the patients were positive for both influenza A and RSV. None of the patients were positive for coronavirus. CONCLUSIONS: Our findings show the importance of influenza virus type A, influenza virus type B, RSV, and adenoviruses associated with ARI in hospitalized patient and the different epidemiological patterns of the viruses in Tabriz, Iran.


title: Nasal Infection of Enterovirus D68 Leading to Lower Respiratory Tract Pathogenesis in Ferrets (Mustela putorius furo)

text: Data from EV-D68-infected patients demonstrate that pathological changes in the lower respiratory tract are principally characterized by severe respiratory illness in children and acute flaccid myelitis. However, lack of a suitable animal model for EV-D68 infection has limited the study on the pathogenesis of this critical pathogen, and the development of a vaccine. Ferrets have been widely used to evaluate respiratory virus infections. In the current study, we used EV-D68-infected ferrets as a potential animal to identify impersonal indices, involving clinical features and histopathological changes in the upper and lower respiratory tract (URT and LRT). The research results demonstrate that the EV-D68 virus leads to minimal clinical symptoms in ferrets. According to the viral load detection in the feces, nasal, and respiratory tracts, the infection and shedding of EV-D68 in the ferret model was confirmed, and these results were supported by the EV-D68 VP1 immunofluorescence confocal imaging with α2,6-linked sialic acid (SA) in lung tissues. Furthermore, we detected the inflammatory cytokine/chemokine expression level, which implied high expression levels of interleukin (IL)-1a, IL-8, IL-5, IL-12, IL-13, and IL-17a in the lungs. These data indicate that systemic observation of responses following infection with EV-D68 in ferrets could be used as a model for EV-D68 infection and pathogenesis.


title: Multiple gastric involvement by myeloid antigen CD13‐positive non‐secretory plasma cell leukaemia

text: Gastrointestinal tract involvement is a rare complication of plasma cell neoplasia. We present a case of non‐secretory type primary plasma cell leukaemia (PCL) with multiple gastric involvement. Dual surface antigen analysis of bone marrow cells revealed that atypical plasma cells coexpressed CD38 and myeloid antigen CD13. Upper gastrointestinal endoscopy disclosed multiple submucosal masses in the body of the stomach. Endoscopic biopsy specimens showed marked infiltration of atypical plasma cells consistent with a diagnosis of gastric involvement by PCL. Since CD13 antigen is identical to aminopeptidase N, a membrane‐bound glycoprotein thought to be involved in the process of tumour invasion, CD13 expression on neoplastic plasma cells may be related to the gastric involvement in this patient.


title: The determinants of Chinese visitors to Australia: A dynamic demand analysis

text: Although China has progressively become an important inbound tourism market for Australia, its demand elasticities have been little studied to date. This study examines the determinants of Chinese visitors to Australia using a dynamic time-series estimator. Interesting findings include a high income elasticity as a source of the continuous doubledigit growth rates in Chinese arrivals that Australia has experienced over the past two decades, together with relatively high total trip price elasticities for both short run and long run. A trend of Chinese outbound to Australia is also identified. From a policy perspective, the results confirm that keeping a low cost of visiting Australia, both ground and travel costs, is a good strategy to secure greater numbers of Chinese tourists.


title: Clinical features, diagnostics, and outcomes of patients presenting with acute respiratory illness: a comparison of patients with and without COVID-19

text: BACKGROUND: Emerging data on the clinical presentation, diagnostics, and outcomes of patients with COVID-19 have largely been presented as case series. Few studies have compared these clinical features and outcomes of COVID-19 to other acute respiratory illnesses. METHODS: We examined all patients presenting to an emergency department in San Francisco, California between February 3 and March 31, 2020 with an acute respiratory illness who were tested for SARS-CoV-2. We determined COVID-19 status by PCR and metagenomic next generation sequencing (mNGS). We compared demographics, comorbidities, symptoms, vital signs, and laboratory results including viral diagnostics using PCR and mNGS. Among those hospitalized, we determined differences in treatment (antibiotics, antivirals, respiratory support) and outcomes (ICU admission, ICU interventions, acute respiratory distress syndrome, cardiac injury). FINDINGS: In a cohort of 316 patients, 33 (10%) tested positive for SARS-CoV-2; 31 patients, all without COVID-19, tested positive for another respiratory virus (16%). Among patients with additional viral testing, no co-infections with SARS-CoV-2 were identified by PCR or mNGS. Patients with COVID-19 reported longer symptoms duration (median 7 vs. 3 days), and were more likely to report fever (82% vs. 44%), fatigue (85% vs. 50%), and myalgias (61% vs 27%); p<0.001 for all comparisons. Lymphopenia (55% vs 34%, p=0.018) and bilateral opacities on initial chest radiograph (55% vs. 24%, p=0.001) were more common in patients with COVID-19. Patients with COVID-19 were more often hospitalized (79% vs. 56%, p=0.014). Of 186 hospitalized patients, patients with COVID-19 had longer hospitalizations (median 10.7d vs. 4.7d, p<0.001) and were more likely to develop ARDS (23% vs. 3%, p<0.001). Most comorbidities, home medications, signs and symptoms, vital signs, laboratory results, treatment, and outcomes did not differ by COVID-19 status. INTERPRETATION: While we found differences in clinical features of COVID-19 compared to other acute respiratory illnesses, there was significant overlap in presentation and comorbidities. Patients with COVID-19 were more likely to be admitted to the hospital, have longer hospitalizations and develop ARDS, and were unlikely to have co-existent viral infections. These findings enhance understanding of the clinical characteristics of COVID-19 in comparison to other acute respiratory illnesses.


title: Integrating Biomedical, Ecological, and Sustainability Sciences to Manage Emerging Infectious Diseases

text: Globalization accelerates the mobilization of microorganisms via international trade and transport. Growth in population, increasing connectivity, and rapid urbanization all exacerbate the consequent risk of pandemics of zoonotic diseases. Global problems require global solutions, particularly the co-ordination of international research in biomedical sciences, global ecology, and sustainability.


title: Comment on “Central Nervous System Involvement by Severe Acute Respiratory Syndrome Coronavirus ‐2 (SARS‐CoV‐2)”

text: A very interesting report, for the first time, provided direct evidence that the ongoing pandemic etiological agent, SARS‐CoV‐2, may be able to directly infect central nervous system (CNS) through an endothelial route. If proven true, this may explain frequent neurological symptoms associated with severe COVID‐19 diseases. A corresponding therapeutic intervention will be urgently needed to prevent such dangerous infections of CNS and associated high mortality rate. This article is protected by copyright. All rights reserved.


title: Diagnostic Evaluation of Pulmonary Abnormalities in Patients with Hematologic Malignancies and Hematopoietic Cell Transplantation

text: Pulmonary complications (PC) of hematologic malignancies and their treatments are common causes of morbidity and mortality. Early diagnosis is challenging due to host risk factors, clinical instability, and provider preference. Delayed diagnosis impairs targeted treatment and may contribute to poor outcomes. An integrated understanding of clinical risk and radiographic patterns informs a timely approach to diagnosis and treatment. There is little prospective evidence guiding optimal modality and timing of minimally invasive lung sampling; however, a low threshold for diagnostic bronchoscopy during the first 24 to 72 hours after presentation should be a guiding principle in high-risk patients.


title: Ad astra per aspera (Through Hardships to the Stars): Lessons Learned from the First National Virtual APDS Meeting, 2020

text: OBJECTIVE: After COVID-19 rendered in-person meetings for national societies impossible in the spring of 2020, the leadership of the Association of Program Directors in Surgery (APDS) innovated via a virtual format in order to hold its national meeting. DESIGN: APDS leadership pre-emptively considered factors that would be important to attendees including cost, value, time, professional commitments, education, sharing of relevant and current information, and networking. SETTING: The meeting was conducted using a variety of virtual formats including a web portal for entry, pre-ecorded poster and oral presentations on the APDS website, interactive panels via a web conferencing platform, and livestreaming. PARTICIPANTS: There were 298 registrants for the national meeting of the APDS, and 59 participants in the New Program Directors Workshop. The registrants and participants comprised medical students, residents, associate program directors, program directors, and others involved in surgical education nationally. RESULTS: There was no significant difference detected for high levels of participant satisfaction between 2019 and 2020 for the following items: overall program rating, topics and content meeting stated objectives, relevant content to educational needs, educational format conducive to learning, and agreement that the program will improve competence, performance, communication skills, patient outcomes, or processes of care/healthcare system performance. CONCLUSIONS: A virtual format for a national society meeting can provide education, engagement, and community, and the lessons learned by the APDS in the process can be used by other societies for utilization and further improvement.


title: Review of international efforts to strengthen the global outbreak response system since the 2014–16 West Africa Ebola Epidemic

text: The 2014–16 West Africa Ebola epidemic was a watershed moment for global health. The outbreak galvanized global action around strengthening infectious disease prevention, detection and response capabilities. We examined the nascent landscape of international programmes, initiatives and institutions established in the aftermath of the 2014–16 Ebola outbreak with the aim of assessing their progress to date to illustrate the current state of the world’s global health security architecture. We also compare these efforts with shortcomings in epidemic management documented during the epidemic, and underscore remaining gaps in regional and global epidemic response capabilities that might benefit from additional programmatic and financial support. Notably, most of the post-Ebola initiatives considered in this analysis have yet to meet their financial goals. Operational progress has also been limited, revealing a need for continued investments to improve outbreak surveillance and detection capabilities specifically. Furthermore, our review highlighted the dominance of the USA and Europe in leading and financing efforts to coordinate long-term recovery efforts in West Africa, strengthen health systems across the continent, and enhance global preparedness for future epidemics, raising important questions about ownership of global health security efforts in non-Western regions of the world. Finally, the lack of transparency and available data on these initiatives’ activities and budgets also complicate efforts to project their impacts on the global health security landscape.


title: Oil and Gas in the Age of COVID‐19 —Where Do They Go From Here?

text: Within the global financial chaos caused by the impacts of COVID‐19, the oil and natural gas production industry has been hit unusually hard. At the onset of the pandemic, oil was already experiencing severe market distress, as global supply exceeded global demand. OPEC had tried to craft a cutback in production, which then turned into a price war between Russia and Saudi Arabia, driving a dramatic decline in global crude oil prices. Then, as the global pandemic emerged and the response of almost all major consuming nations was to bring travel, industry, and workplace commuting to a screeching full stop, the resulting collapse in demand allowed the oil industry to give an object lesson in supply‐demand economics. The bottom fell out of the crude oil price both internationally and domestically for the United States. Figure 1 charts the price of US crude oil at the West Texas Intermediate (WTI) index at Cushing, Oklahoma, from 2007, when the shale era began, to the current situation (the chart presents the data on a rolling‐monthly‐average basis, to smooth out the high level of daily volatility experienced over that entire 13‐year period).


title: ACE2 and prognosis of COVID‐19. Insights from Bartter's and Gitelman's syndromes patients

text: The relationship between Renin‐Angiotensin system (RAS) and COVID‐19 pandemic and, in particular, RAS as part of the CoV‐2 infection process via Angiotensin Converting Enzyme 2 (ACE2), the entry point of SARS‐CoV‐2, has resulted in conflicting suggestions regarding how RAS and its role(s) should inform treating COVID‐19. ACE inhibitors or angiotensin II (Ang)‐type 1 receptor blockers (ARBs), in fact, have been suggested to be avoided as they potentially upregulate ACE2 (1) and, conversely, there are suggestions that ARBs might be beneficial (2) as SARS‐CoV‐2 causing ACE2 downregulation slows the Ang II conversion to the vasodilatory, anti‐inflammatory, antioxidant and antiatherosclerotic Ang 1‐7 (3‐5), and the use of ARBs by blocking the excessive Ang II type‐1 receptors activation, would be beneficial upregulating ACE2 activity and increasing Ang 1‐7 levels. This article is protected by copyright. All rights reserved.