title: Interferon lambda inhibits dengue virus replication in epithelial cells

text: BACKGROUND: In viral disease, infection is controlled at the cellular level by type I interferon (IFN-I), but dengue virus (DENV) has the ability to inhibit this response. Type III interferon, also known as lambda IFN (IFN-III or IFN-λ), is a complementary pathway to the antiviral response by IFN-I. This work analyzed the IFN-λ (IFN-III) mediated antiviral response against DENV serotype 2 (DENV-2) infection. METHODS: Dengue fever patients were sampled to determine their IFN-λ levels by ELISA. To study the IFN-λ response during DENV infection we selected the epithelial cell line C33-A, and we demonstrated that it is permissive to DENV-2 infection. The effect of IFN-λ on virus replication was determined in these cells, in parallel to the expression of IFN-stimulated genes (ISGs), and Suppressor of Cytokine Signaling (SOCS), genes measured by RT-qPCR. RESULTS: We found increased (~1.8 times) serological IFN-λ in dengue fever patients compared to healthy blood donors. IFN-λ inhibited DENV-2 replication in a dose-dependent manner in vitro. The reduction of viral titer corresponded with increased ISG mRNA levels (MX1 and OAS1), with the highest inhibition occurring at ISG’s peak expression. Presence of IFN-negative regulators, SOCS1 and SOCS3, during DENV-2 infection was associated with reduced IFN-λ1 expression. CONCLUSIONS: Evidence described here suggests that IFN-λ is a good candidate inhibitor of viral replication in dengue infection. Mechanisms for the cellular and organismal interplay between DENV and IFN- λ need to be further studied as they could provide insights into strategies to treat this disease. Furthermore, we report a novel epithelial model to study dengue infection in vitro.


title: Telemedicine as a tool for PrEP delivery during the COVID-19 Pandemic in a large HIV Prevention service in Rio de Janeiro-Brazil

text: Abstract COVID-19 public health responses such as social distancing and community containment measures protocols are critical to preventing and containing the spread of coronavirus. Brazil accounts for almost half of Latin American HIV cases and Rio de Janeiro is the city with the second largest number of AIDS. Clinical appointments and pharmacy antiretroviral refills may be impaired due to restricted traffic and possible lockdowns, preventing people living with HIV and those using PrEP from accessing needed antiretrovirals. We hereby describe the telemedicine procedures implemented in a large PrEP delivery in Rio de janeiro in the context of the COVID-19 pandemic. At the initial teleconsultation, individuals undergoe HIV rapid testing and are assessed by phone for PrEP related procedures. Individuals receive a digital prescription to retrieve a 120-day PrEP supply plus two HIV self-test kits. Subsequent follow-up teleconsultations will be performed remotely by phone call, including instructions for the HIV self-test performance, which results are to be sent using a digital picture. Participants will attend the service only for PrEP refill. The use of telemedicine procedures is being effective to avoid PrEP shortage and reduce the time PrEP users spend at the service during the COVID-19 pandemic and social distancing recommendations.


title: Detection of bocavirus DNA in nasopharyngeal aspirates of a child with bronchiolitis

text: Summary We describe a case of bronchiolitis associated with the newly detected human bocavirus (hBoV) in a child with a suspected Noonan syndrome. This is the first report of a bronchiolitis probably linked to hBoV that required intensive care while being accompanied by a congenital heart disease and a history of several episodes of severe respiratory symptoms.


title: Dual activity of niclosamide to suppress replication of integrated HIV-1 and Mycobacterium tuberculosis (Beijing)

text: Abstract The human immunodeficiency virus (HIV) pandemic is driving the re-emergence of tuberculosis (TB) as a global health threat, both by increasing the susceptibility of HIV-infected people to infection with Mycobacterium tuberculosis (Mtb), and increasing the rate of emergence of drug-resistant Mtb. There are several other clinical challenges for treatment of co-infected patients including: expense, pill burden, toxicity, and malabsorption that further necessitate the search for new drugs that may be effective against both pathogens simultaneously. The anti-helminthic niclosamide has been shown to have activity against a laboratory strain of Mtb in liquid culture while bacteriostatic activity against non-replicating M. abscessus was also recently described. Here we extend these findings to further demonstrate that niclosamide inhibits mycobacterial growth in infected human macrophages and mediates potent bacteriostatic activity against the virulent Mtb Beijing strain. Importantly, we provide the first evidence that niclosamide inhibits HIV replication in human macrophages and Jurkat T cells through post-integration effects on pro-virus transcription. The dual antiviral and anti-mycobacterial activity was further observed in an in vitro model of HIV and Mtb co-infection using human primary monocyte-derived macrophages. These results support further investigation of niclosamide and derivatives as anti-retroviral/anti-mycobacterial agents that may reduce clinical challenges associated with multi-drug regimens and drug resistance.


title: The TLR4 Agonist Immunomax Affects the Phenotype of Mouse Lung Macrophages during Respiratory Syncytial Virus Infection

text: In the study, the effect of the TLR4 agonist Immunomax was investigated in vitro and in vivo. In particular, Immunomax was shown to polarize mouse bone marrow macrophages from the M0 and M2 states into the M1 state (ARG1 and iNOS mRNA expression levels were used to identify the mouse M1 and M2 phenotypes). Next, we investigated the prophylactic antiviral effect of Immunomax in both a model of mouse respiratory syncytial virus (RSV) infection and a model of RSV-induced bronchial asthma (BA) exacerbation. In the experiment with RSV-induced BA exacerbation, Immunomax-treated mice were characterized by a significant decrease of the viral load in lung homogenates, an increased amount of M1 macrophages in the lung, a tendency toward Th2-dependent ovalbumin-specific IgG1 antibodies decrease in blood serum, a significant increase in RSV-activated CD4+ T cells secreting IFNγ (Th1 cells), and a simultaneous significant decrease in the amount of CD4(+) cells secreting IL-4 (Th2 cells) in the mouse spleen, which were detected by ELISPOT 1.5 months after experiment. These findings suggest that treatment with the TLR4 agonist Immunomax polarizes the immune response towards antiviral Th1 and may be used for short-term antiviral prophylaxis to prevent acute respiratory viral infections in asthmatics.


title: COVID‐19 in a melanoma patient under treatment with checkpoint‐inhibition

text: SARS‐CoV‐2 poses new challenges in all aspects of healthcare. Patients with preexisting cardio‐vascular conditions are at higher risk of developing severe symptoms and worse outcome. Data also suggest that cancer patients are particularly vulnerable, but differences between tumor entities and cancer treatments may exist. Little is known how cancer treatment engaging immune checkpoints affects the course of COVID‐19.


title: Protein microarrays for systems biology

text: Systems biology holds the key for understanding biological systems on a system level. It eventually holds the key for the treatment and cure of complex diseases such as cancer, diabetes, obesity, mental disorders, and many others. The ‘-omics' technologies, such as genomics, transcriptomics, proteomics, and metabonomics, are among the major driving forces of systems biology. Featured as high-throughput, miniaturized, and capable of parallel analysis, protein microarrays have already become an important technology platform for systems biology. In this review, we will focus on the system level or global analysis of biological systems using protein microarrays. Four major types of protein microarrays will be discussed: proteome microarrays, antibody microarrays, reverse-phase protein arrays, and lectin microarrays. We will also discuss the challenges and future directions of protein microarray technologies and their applications for systems biology. We strongly believe that protein microarrays will soon become an indispensable and invaluable tool for systems biology.


title: H5N1 infection causes rapid mortality and high cytokine levels in chickens compared to ducks

text: Abstract Infection with H5N1 influenza virus is often fatal to poultry with death occurring in hours rather than days. However, whilst chickens may be acutely susceptible, ducks appear to be asymptomatic to H5N1. The mechanisms of disease pathogenesis are not well understood and the variation between different species requires investigation to help explain these species differences. Here we investigated the expression of several key proinflammatory cytokines of chickens and ducks following infection with 2 highly pathogenic H5N1 (A/Muscovy duck/Vietnam/453/2004 (Vt453) and A/Duck/Indramayu/BBVW/109/2006 (Ind109)) and a low-pathogenic H5N3 influenza virus (A/Duck/Victoria/1462/2008 (Vc1462)). H5N1 viruses caused fatal infections in chickens as well as high viral loads and increased production of proinflammatory molecules when compared to ducks. Cytokines, including Interleukin 6 (IL6) and the acute phase protein Serum Amyloid A (SAA), were rapidly induced at 24h post infection with H5N1. In contrast, low induction of these cytokines appeared in ducks and only at later times during the infection period. These observations support that hypercytokinemia may contribute to pathogenesis in chickens, whilst the lower cytokine response in ducks may be a factor in their apparent resistance to disease and decreased mortality.


title: Dorsal root ganglia may be reservoirs of viral infection in multiple sclerosis

text: Abstract There are presently two competitive theories that attempt to explain the etiology of multiple sclerosis (MS). Briefly summarized, they are: 1. An infection, probably of viral type, may attack the oligodendroglia of the central nervous system; or, 2. An autoimmune process may begin with an infection of the peripheral lymphatic immune system, producing antibodies that cross the blood-brain barrier, leading to myelinoclasia. Since 1935, research has been directed toward myelin of the central nervous system and the myelin sheaths of peripheral nerve; however, dorsal root and cranial sensory ganglia (DRG) have apparently not been studied. The present hypothesis states that an infectious agent (probably viral) finds privileged sanctuary in the dorsal root and cranial sensory ganglia (DRG): thereafter periodically invading the spinal cord, brain, or peripheral nerve. Previously reported erratic spinal fluid viral titers and cultures can be explained by differences in the anatomy of the DRG in which there is a variable and limited contact of spinal fluid with sensory ganglia. Clues to this hypothesis were noted by the author during routine neurological examinations of patients with MS, in which sensory signs and symptoms were frequently encountered. This clinical observation has also been reported by others who found such symptoms in 75% of MS patients, ranking second only to incoordination.


title: Position Paper on Road Map for RNA Virus Research in India

text: The Indian subcontinent with its population density, climatic conditions, means of subsistence, socioeconomic factors as well as travel and tourism presents a fertile ground for thriving of RNA viruses. Despite being pathogens of huge significance, there is very little focus on research into the biology and pathogenesis of RNA viruses in India. Studies on epidemiology and disease burden, risk factors, the immune response to RNA viruses, circulating virus strains and virus evolution, animal models of disease, antivirals and vaccines are strikingly absent. Emerging RNA viruses such as Zika virus, Nipah virus and Crimean-Congo haemorrhagic fever virus are a matter of grave concern to India. Here we summarize the outcome of the India|EMBO symposium on “RNA viruses: immunology, pathogenesis and translational opportunities” organized at Faridabad, National Capital Region, India, on March 28–30, 2018. The meeting focused on RNA viruses (non-HIV), and both national and international experts on RNA viruses covered topics ranging from epidemiology, immune response, virus evolution and vaccine trials concerning RNA viruses. The aim of the symposium was to create a road map for RNA virus research in India. Both concrete and tentative ideas pointing towards short-term and long-term goals were presented with recommendations for follow-up at government level.


title: Critical care and the global burden of critical illness in adults

text: Summary Critical care has evolved from treatment of poliomyelitis victims with respiratory failure in an intensive care unit to treatment of severely ill patients irrespective of location or specific technology. Population-based studies in the developed world suggest that the burden of critical illness is higher than generally appreciated and will increase as the population ages. Critical care capacity has long been needed in the developing world, and efforts to improve the care of the critically ill in these settings are starting to occur. Expansion of critical care to handle the consequences of an ageing population, natural disasters, conflict, inadequate primary care, and higher-risk medical therapies will be challenged by high costs at a time of economic constraint. To meet this challenge, investigators in this discipline will need to measure the global burden of critical illness and available critical-care resources, and develop both preventive and therapeutic interventions that are generalisable across countries.


Identification of Respiratory Viral Infection in Hematopoietic Stem Cell Transplant Recipients - Impact on Non Relapse Mortality


title: Challenges and strategies to research ethics in conducting COVID‐19 research

text: The number of research involving human subjects on coronavirus disease 2019 (COVID‐19) is surging, bringing challenges to the ethical review committee (ERC) in terms of reviewing speed and special ethical considerations under the pandemic. However, the existing ethical review system and regulations have their limitations to meet the demand for a prompt and efficient epidemic control. Since the research under the public health emergency is different from that carried out in familiar situations to design and implementation, the strategy for a satisfactory ERC response should balance the duty of protecting individual participants as well as the special public needs derived from the disease control. It is suggested that the ethical review‐related regulations need to be updated, and a unified supervision system to the overall ERC is required. ERC collaboration, capacity‐improving and efficiency‐improving measures need to be taken. With respect to the reviewing guidelines, it is suggested that the international norms should be explained with more consideration of the local condition and the exceptional circumstances in this public health emergency. A joint effort needs to be taken for better research conduction.


title: Viral Etiology of Chronic Obstructive Pulmonary Disease Exacerbations during the A/H1N1pdm09 Pandemic and Postpandemic Period

text: Viral infections are one of the main causes of acute exacerbations of chronic obstructive pulmonary disease (AE-COPD). Emergence of A/H1N1pdm influenza virus in the 2009 pandemic changed the viral etiology of exacerbations that were reported before the pandemic. The aim of this study was to describe the etiology of respiratory viruses in 195 Spanish patients affected by AE-COPD from the pandemic until the 2011-12 influenza epidemic. During the study period (2009–2012), respiratory viruses were identified in 48.7% of samples, and the proportion of viral detections in AE-COPD was higher in patients aged 30–64 years than ≥65 years. Influenza A viruses were the pathogens most often detected during the pandemic and the following two influenza epidemics in contradistinction to human rhino/enteroviruses that were the main viruses causing AE-COPD before the pandemic. The probability of influenza virus detection was 2.78-fold higher in patients who are 30–64 years old than those ≥65. Most respiratory samples were obtained during the pandemic, but the influenza detection rate was higher during the 2011-12 epidemic. There is a need for more accurate AE-COPD diagnosis, emphasizing the role of respiratory viruses. Furthermore, diagnosis requires increased attention to patient age and the characteristics of each influenza epidemic.


title: Creeping Through the Backdoor: Disruption in Medicine and Health

text: Can disruption happen when no one notices? Disruptive technologies and processes are fundamentally starting to up-end how medicines and health systems benefit patients but the question is whether health systems are ready for them. This paper will briefly review the business strategy and management literature on topics such as disruption and “black swan” theories of change, before turning to discuss some of the areas where change is affecting medicine and healthcare. Such areas include the emergence of cell and gene therapies, the economics of cures, digital technologies, mobile apps, social media, supply chain technologies such as drones and online distribution, universal health coverage and funding, and consumerisation of healthcare. The question to be asked is whether these sorts of changes are “disruptive” or whether they were coming for a long time and it is just that health systems are slow to change. It could be argued that while perhaps unexpected by day-to-day practitioners in healthcare, in fact, many of the changes now starting to affect the health and medicines sector have been affecting other sectors such as technology, finance and communications for decades.


Obesity and COVID-19: The Clash of Two Pandemics


title: A review of mathematical modeling, artificial intelligence and datasets used in the study, prediction and management of COVID-19

text: In the past few months, several works were published in regards to the dynamics and early detection of COVID-19 via mathematical modeling and Artificial intelligence (AI). The aim of this work is to provide the research community with comprehensive overview of the methods used in these studies as well as a compendium of available open source datasets in regards to COVID-19. In all, 61 journal articles, reports, fact sheets, and websites dealing with COVID-19 were studied and reviewed. It was found that most mathematical modeling done were based on the Susceptible-Exposed-Infected-Removed (SEIR) and Susceptible-infected-recovered (SIR) models while most of the AI implementations were Convolutional Neural Network (CNN) on X-ray and CT images. In terms of available datasets, they include aggregated case reports, medical images, management strategies, healthcare workforce, demography, and mobility during the outbreak. Both Mathematical modeling and AI have both shown to be reliable tools in the fight against this pandemic. Several datasets concerning the COVID-19 have also been collected and shared open source. However, much work is needed to be done in the diversification of the datasets. Other AI and modeling applications in healthcare should be explored in regards to this COVID-19.


title: Hypothesized behavioral host manipulation by SARS-CoV2 / COVID-19 infection

text: Abstract Although not widely studied, behavioral host manipulation by various pathogens has been documented. Host manipulation is the process by which a pathogen evolves adaptations to manipulate the behavior of the host to maximize reproduction (Ro) of the pathogen. The most notable example is rabies. When a host is infected with the rabies virus it gets into the host’s central nervous system and triggers hyper aggression. The virus is also present in the rabid animal’s saliva so being bitten transmits the infection to a new host and the old host is left to eventually die if untreated. Toxoplasmosis is another example. When mice are infected they demonstrate a fearlessness toward cats, thus increasing their chances of being eaten. Toxoplasmosis needs the digestive tract of the feline to survive. Recent studies have shown that exposure to toxoplasmosis in humans (e.g., through cat feces) has also been associated with behavioral changes that are predicted to enhance the spread of the pathogen. Even the common influenza virus has been shown to selectively increase in-person sociality during the 48-hour incubation period, thus producing an obvious vector for transmission. Here we hypothesize that the novel coronavirus, SARS-CoV2, which produces the COVID-19 disease may produce similar host manipulations that maximize its transmission between humans.


title: Pneumonia in children admitted to the national referral hospital in Bhutan: A prospective cohort study

text: Abstract Objectives The study aim was to describe the etiological profile and clinical characteristics of pneumonia among children hospitalized in Thimphu, Bhutan. Methods This prospective study enrolled children aged 2–59 months admitted to the Jigme Dorji Wangchuck National Referral Hospital with World Health Organization (WHO)-defined clinical pneumonia. Demographic and clinico-radiological data were collected through questionnaires, physical examination, and chest radiography. Blood samples and nasopharyngeal washing were collected for microbiological analysis including culture and molecular methods. Results From July 2017 to June 2018, 189 children were enrolled, of which 53.4% were infants. Pneumonia-related admissions were less frequent over the winter. Chest radiographies were obtained in 149 children; endpoints included pneumonia in 39 cases (26.2%), other infiltrates in 31 (20.8%), and were normal in 79 children (53.0%). Non-contaminated bacterial growth was detected in 8/152 (5.3%) blood cultures, with only two cases of Streptococcus pneumoniae. Viral detection in upper respiratory secretions was common, with at least one virus detected in 103/115 (89.6%). The three most-commonly isolated viruses were respiratory syncytial virus (52/115; 45.2%), rhinovirus (42/115; 36.5%), and human parainfluenza virus (19/115; 16.5%). A third of patients with viral infections showed mixed infections. Case fatality rate was 3.2% (6/189). Conclusion Respiratory viral infections predominated among this cohort of WHO-defined clinical pneumonia cases, whereas bacterial aetiologies were uncommon, highlighting the epidemiologic transition that Bhutan seems to have reached.


title: Detection of the New Human Coronavirus HKU1: A Report of 6 Cases

text: Background. Human coronavirus HKU1 (HCoV-HKU1), a new group 2 coronavirus, was first characterized in 2005 from 2 adults with pneumonia in Hong Kong, China. To the best of our knowledge, there is no other report to date about the detection of this new virus. We report a molecular method allowing for the detection of HCoV-HKU1 and also report the clinical presentation of 6 infected patients. Methods. We screened 141 specimens (135 nasal samples and 6 stool samples) received in February and March 2005 in our laboratory and obtained from 135 hospitalized patients (61.5% of whom were <5 years old and 34.1% of whom were >20 years old) for HCoV-HKU1. Results. HCoV-HKU1 was detected in 6 (4.4%) of the 135 nasal specimens and in 2 (33.3%) of the 6 stool samples; the positive samples were obtained from 6 patients (5 children and 1 adult). The clinical presentation of these 6 patients was as follows: 3 were admitted to the hospital for acute enteric disease resulting in severe dehydration associated with upper respiratory symptoms; 1 had fever, otitis, and febrile seizure; 1 had a sample obtained to investigate failure to thrive; and 1 had a sample obtained for exploration of X-linked agammaglobulinemia and hyperleucocytosis. Conclusion. HCoV-HKU1 can be detected in respiratory and stool samples from children and adults in a part of the world other than Hong Kong. Our results suggest that HCoV-HKU1 could be associated with respiratory and enteric diseases, and its detection can be related to a persistent asymptomatic infection in patients with poor underlying conditions.


title: Evaluation of Two Commercial Real-Time PCR Kits for Aspergillus DNA Detection in Bronchoalveolar Lavage Fluid in Patients with Invasive Pulmonary Aspergillosis

text: Invasive pulmonary aspergillosis (IPA) is a common complication of immunosuppression. Rapid diagnosis using molecular techniques is essential to improve patient survival. PCR techniques are promising in enhancing Aspergillus detection in blood and respiratory samples. We evaluate for the first time the performances of two commercial real-time PCR kits, the A. fumigatus Bio-Evolution and the MycoGENIE A. fumigatus for the detection of A. fumigatus DNA in bronchoalveolar lavage (BAL) from patients with and without IPA. Seventy-three BAL samples were included. Thirty-one of them corresponded to patients with probable IPA, 11 to patients with possible IPA, and 31 to patients without aspergillosis, according to the 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. In the probable IPA group, A. fumigatus Bio-Evolution and the MycoGENIE A. fumigatus real-time PCR kits showed a specificity of 100% and a sensitivity of 81% and 71%, respectively. The A. fumigatus Bio-Evolution detected Aspergillus DNA in the 14 BAL samples with a positive Aspergillus culture result, whereas the MycoGENIE A. fumigatus PCR result was positive only for 12. In the possible IPA group, there were no positive real-time PCR or positive Aspergillus culture results. For the patients without aspergillosis, no positive result was observed for real-time PCR kit, despite the presence of various other non-Aspergillus pathogens in this group. Our study demonstrates an excellent specificity and a good sensitivity of A. fumigatus DNA detection in BAL samples with both kits.


title: Descriptive review and evaluation of the functioning of the International Health Regulations (IHR) Annex 2

text: BACKGROUND: The International Health Regulations (IHRs) (2005) was developed with the aim of governing international responses to public health risks and emergencies. The document requires all 194 World Health Organization (WHO) Member States to detect, assess, notify and report any potential public health emergency of international concern (PHEIC) under specific timelines. Annex 2 of the IHR outlines decision-making criteria for State-appointed National Focal Points (NFP) to report potential PHEICs to the WHO, and is a critical component to the effective functioning of the IHRs. METHODS: The aim of the study was to review and evaluate the functioning of Annex 2 across WHO-reporting States Parties. Specific objectives were to ascertain NFP awareness and knowledge of Annex 2, practical use of the tool, activities taken to implement it, its perceived usefulness and user-friendliness. Qualitative telephone interviews, followed by a quantitative online survey, were administered to NFPs between October, 2009 and February, 2010. RESULTS: A total of 29 and 133 NFPs participated in the qualitative and quantitative studies, respectively. Qualitative interviews found most NFPs had a strong working knowledge of Annex 2; perceived the tool to be relevant and useful for guiding decisions; and had institutionalized management, legislation and communication systems to support it. NFPs also perceived Annex 2 as human and disease-centric, and emphasized its reduced applicability to potential PHEICs involving bioterrorist attacks, infectious diseases among animals, radio-nuclear and chemical spills, and water- or food-borne contamination. Among quantitative survey respondents, 88% reported having excellent/good knowledge of Annex 2; 77% reported always/usually using Annex 2 for assessing potential PHEICs; 76% indicated their country had some legal, regulatory or administrative provisions for using Annex 2; 95% indicated Annex 2 was always/usually useful for facilitating decisions regarding notifiability of potential PHEICs. CONCLUSION: This evaluation, including a large sample of WHO-reporting States Parties, found that the IHR's Annex 2 is perceived as useful for guiding decisions about notifiability of potential PHEICs. There is scope for the WHO to expand training and guidance on application of the IHR's Annex 2 to specific contexts. Continued monitoring and evaluation of the functioning of the IHR is imperative to promoting global health security.


title: Interventions to mitigate early spread of SARS-CoV-2 in Singapore: a modelling study

text: BACKGROUND: Since the coronavirus disease 2019 outbreak began in the Chinese city of Wuhan on Dec 31, 2019, 68 imported cases and 175 locally acquired infections have been reported in Singapore. We aimed to investigate options for early intervention in Singapore should local containment (eg, preventing disease spread through contact tracing efforts) be unsuccessful. METHODS: We adapted an influenza epidemic simulation model to estimate the likelihood of human-to-human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a simulated Singaporean population. Using this model, we estimated the cumulative number of SARS-CoV-2 infections at 80 days, after detection of 100 cases of community transmission, under three infectivity scenarios (basic reproduction number [R(0)] of 1·5, 2·0, or 2·5) and assuming 7·5% of infections are asymptomatic. We first ran the model assuming no intervention was in place (baseline scenario), and then assessed the effect of four intervention scenarios compared with a baseline scenario on the size and progression of the outbreak for each R(0) value. These scenarios included isolation measures for infected individuals and quarantining of family members (hereafter referred to as quarantine); quarantine plus school closure; quarantine plus workplace distancing; and quarantine, school closure, and workplace distancing (hereafter referred to as the combined intervention). We also did sensitivity analyses by altering the asymptomatic fraction of infections (22·7%, 30·0%, 40·0%, and 50·0%) to compare outbreak sizes under the same control measures. FINDINGS: For the baseline scenario, when R(0) was 1·5, the median cumulative number of infections at day 80 was 279 000 (IQR 245 000–320 000), corresponding to 7·4% (IQR 6·5–8·5) of the resident population of Singapore. The median number of infections increased with higher infectivity: 727 000 cases (670 000–776 000) when R(0) was 2·0, corresponding to 19·3% (17·8–20·6) of the Singaporean population, and 1 207 000 cases (1 164 000–1 249 000) when R(0) was 2·5, corresponding to 32% (30·9–33·1) of the Singaporean population. Compared with the baseline scenario, the combined intervention was the most effective, reducing the estimated median number of infections by 99·3% (IQR 92·6–99·9) when R(0) was 1·5, by 93·0% (81·5–99·7) when R(0) was 2·0, and by 78·2% (59·0 −94·4) when R(0) was 2·5. Assuming increasing asymptomatic fractions up to 50·0%, up to 277 000 infections were estimated to occur at day 80 with the combined intervention relative to 1800 for the baseline at R(0) of 1·5. INTERPRETATION: Implementing the combined intervention of quarantining infected individuals and their family members, workplace distancing, and school closure once community transmission has been detected could substantially reduce the number of SARS-CoV-2 infections. We therefore recommend immediate deployment of this strategy if local secondary transmission is confirmed within Singapore. However, quarantine and workplace distancing should be prioritised over school closure because at this early stage, symptomatic children have higher withdrawal rates from school than do symptomatic adults from work. At higher asymptomatic proportions, intervention effectiveness might be substantially reduced requiring the need for effective case management and treatments, and preventive measures such as vaccines. FUNDING: Singapore Ministry of Health, Singapore Population Health Improvement Centre.


Murine Typhus from Vietnam, Imported into Japan


title: Inactivation effects of electrostatic field on Bacillus subtilis

text: Abstract In order to study the inactivation effects of electrostatic field of electret films on Bacillus subtilis, a plane–plane electrode system was used to simulate the electric field of the electret films and the viability of B. subtilis affected by electrostatic field for different applying durations was investigated. It was found that the survival ratio of B. subtilis can be considerably affected by the field and duration. It was also found that the viability of bacillus decreases with the increase of the duration. In addition, the comparative survival ratio (CSR) of B. subtilis decreases to 35% even during a short duration as the applied field reaches an enough high value of more than 15kV/cm. These indicated that the uniform field inactivated the viability of B. subtilis availability. Based on the inactivation effect of the applied field on the B. subtilis, the effectiveness of charged polypropylene films on the inactivation of B. subtilis was measured and discussed.


title: Correlation between Chest CT Findings and Clinical Features of 211 COVID-19 Suspected Patients in Wuhan, China

text: BACKGROUND: Chest CT has been widely used to assess the pulmonary involvement in COVID-19. We aimed to investigate the correlation between chest CT and clinical features in COVID-19 suspected patients with or without fever. METHODS: We retrospectively enrolled 211 COVID-19 suspected patients who underwent both chest CT and RT-PCR in Wuhan, China. The performance of CT in patients having relevant onset symptoms with fever (n=141) and without fever (n=70) were assessed respectively. RESULTS: The sensitivity of CT for COVID-19 was 97.3% with AUC of 0.71 (95% CI 0.66-0.76). There were 141 suspected patients with fever and 70 without fever. In fever group, four variables were screened to establish the basic model: age, monocyte, red blood cell, and hypertension. The AUC of basic model was 0.72 (95% CI 0.63-0.81) while CT-aided model was 0.77 (95% CI 0.68-0.85), with significantly difference (P＜0.05). In non-fever group, only dry cough was screened out to establish the basic model, AUC was 0.76 (95% CI 0.64-0.88), which made no significantly difference than CT-aided model (P=0.08). CONCLUSIONS: Chest CT has a high sensitivity on COVID-19, and it can improve the diagnostic accuracy for COVID-19 suspected patients with fever in initial screen, while its value for non-fever patients remains questionable.


title: Targeting the host or the virus: Current and novel concepts for antiviral approaches against influenza virus infection

text: Abstract Influenza epidemics and pandemics are constant threats to human health. The application of antiviral drugs provides an immediate and direct control of influenza virus infection. At present, the major strategy for managing patients with influenza is through targeting conserved viral proteins critical for viral replication. Two classes of conventional antiviral drugs, the M2 ion channel blockers and the neuraminidase inhibitors, are frequently used. In recent years, increasing levels of resistance to both drug classes has become a major public health concern, highlighting the urgent need for the development of alternative treatments. Novel classes of antiviral compounds or biomolecules targeting viral replication mechanism are under development, using approaches including high-throughput small-molecule screening platforms and structure-based designs. In response to influenza virus infection, host cellular mechanisms are triggered to defend against the invaders. At the same time, viruses as obligate intracellular pathogens have evolved to exploit cellular responses in support of their efficient replication, including antagonizing the host type I interferon response as well as activation of specific cellular pathways at different stages of the replication cycle. Numerous studies have highlighted the possibility of targeting virus–host interactions and host cellular mechanisms to develop new treatment regimens. This review aims to give an overview of current and novel concepts targeting the virus and the host for managing influenza.


title: Potential enhancement of osteoclastogenesis by severe acute respiratory syndrome coronavirus 3a/X1 protein

text: Severe acute respiratory syndrome coronavirus (SARS-CoV) causes a lung disease with high mortality. In addition, osteonecrosis and bone abnormalities with reduced bone density have been observed in patients following recovery from SARS, which were partly but not entirely explained by the short-term use of steroids. Here, we demonstrate that human monocytes, potential precursors of osteoclasts, partly express angiotensin converting enzyme 2 (ACE2), a cellular receptor of SARS-CoV, and that expression of an accessory protein of SARS-CoV, 3a/X1, in murine macrophage cell line RAW264.7 cells, enhanced NF-κB activity and differentiation into osteoclast-like cells in the presence of receptor activator of NF-κB ligand (RANKL). Furthermore, human epithelial A549 cells expressed ACE2, and expression of 3a/X1 in these cells up-regulated TNF-α, which is known to accelerate osteoclastogenesis. 3a/X1 also enhanced RANKL expression in mouse stromal ST2 cells. These findings indicate that SARS-CoV 3a/X1 might promote osteoclastogenesis by direct and indirect mechanisms.


title: RESOLVIENDO UNA DE LAS PIEZAS DEL PUZLE: COVID-19 Y DIABETES TIPO 2

text: Resumen La eclosión de la pandemia por COVID-19 supone un reto de enormes dimensiones y, dada la gran presencia de diabetes mellitus tipo2 en la población actual, hace que sea un problema de salud en el que centrar nuestros esfuerzos para dar la mejor respuesta a nuestros pacientes, que son más vulnerables al desarrollo de la infección y candidatos a presentar cuadros clínicos más graves. Este documento pretende abordar la relación entre la infección por COVID-19 y la DM2. Para ello analizaremos brevemente qué datos epidemiológicos sustentan esta asociación y, posteriormente, se profundizará en los mecanismos fisiopatológicos que podrían conectar ambas enfermedades. Abstract The emergence of the COVID-19 pandemic represents an enormous challenge. Given the considerable presence of type 2 diabetes mellitus in the current population, the pandemic is a health issue that requires an effort to provide better responses to our patients who are more vulnerable to the onset of infection and who are candidates for presenting more severe symptoms. This document attempts to address the relationship between COVID-19 infection and type 2 diabetes mellitus. To this end, we will briefly analyse whether the epidemiological data support this association and, subsequently, go in depth on the pathophysiological mechanisms that might connect the two diseases.


title: Binding mechanism of coronavirus main proteinase with ligands and its implication to drug design against SARS()

text: In order to stimulate the development of drugs against severe acute respiratory syndrome (SARS), based on the atomic coordinates of the SARS coronavirus main proteinase determined recently [Science 13 (May) (2003) (online)], studies of docking KZ7088 (a derivative of AG7088) and the AVLQSGFR octapeptide to the enzyme were conducted. It has been observed that both the above compounds interact with the active site of the SARS enzyme through six hydrogen bonds. Also, a clear definition of the binding pocket for KZ7088 has been presented. These findings may provide a solid basis for subsite analysis and mutagenesis relative to rational design of highly selective inhibitors for therapeutic application. Meanwhile, the idea of how to develop inhibitors of the SARS enzyme based on the knowledge of its own peptide substrates (the so-called “distorted key” approach) was also briefly elucidated.


title: First detection of Nebovirus and Norovirus from cattle in China

text: Neboviruses and genogroup III noroviruses (NoVsGIII) are causative agents of calf diarrhea. The purpose of this study was to investigate the presence of neboviruses and noroviruses in cattle in China. Twenty-eight diarrhea fecal samples collected from 5 different farms were analyzed by RT-PCR. The results showed that 3 nebovirus positive samples were detected on 2 farms, with two strains being related to Bo/DijonA216/06/FR strain and the other one clustering with NB-like strains. Meanwhile, 3 norovirus positive samples were detected on 3 farms, all of which belonged to genotype 1. Our results confirmed the presence of neboviruses and NoVsGIII in China for the first time, and supported the presence of a novel “DijonA216-like” nebovirus genotype.


title: Influenza Virus in a Natural Host, the Mallard: Experimental Infection Data

text: Wild waterfowl, particularly dabbling ducks such as mallards (Anas platyrhynchos), are considered the main reservoir of low-pathogenic avian influenza viruses (LPAIVs). They carry viruses that may evolve and become highly pathogenic for poultry or zoonotic. Understanding the ecology of LPAIVs in these natural hosts is therefore essential. We assessed the clinical response, viral shedding and antibody production of juvenile mallards after intra-esophageal inoculation of two LPAIV subtypes previously isolated from wild congeners. Six ducks, equipped with data loggers that continually monitored body temperature, heart rate and activity, were successively inoculated with an H7N7 LPAI isolate (day 0), the same H7N7 isolate again (day 21) and an H5N2 LPAI isolate (day 35). After the first H7N7 inoculation, the ducks remained alert with no modification of heart rate or activity. However, body temperature transiently increased in four individuals, suggesting that LPAIV strains may have minor clinical effects on their natural hosts. The excretion patterns observed after both re-inoculations differed strongly from those observed after the primary H7N7 inoculation, suggesting that not only homosubtypic but also heterosubtypic immunity exist. Our study suggests that LPAI infection has minor clinically measurable effects on mallards and that mallard ducks are able to mount immunological responses protective against heterologous infections. Because the transmission dynamics of LPAIVs in wild populations is greatly influenced by individual susceptibility and herd immunity, these findings are of high importance. Our study also shows the relevance of using telemetry to monitor disease in animals.


title: Turning biodefense dollars into products

text: Five years after the US anthrax attacks, and more than two years after BioShield legislation was ratified, a survey reveals that biodefense funding has thus far produced only a handful of products for clinical development.


Increased sFLT1/PlGF ratio in COVID‐19: a novel link to Angiotensin II‐mediated endothelial dysfunction


title: In vivo and in vitro models of demyelinating diseases: Tropism of the JHM strain of murine hepatitis virus for cells of glial origin

text: Abstract Infection of mice with the neurotropic JHM strain of murine hepatitis virus causes demyelinating lesions resulting from an infection of the oligodendroglia. This was most evident in mice inoculated intraperitoneally with JHM. Such CNS lesions were not observed in mice inoculated intraperitoneally with the MHV3 strain. An in vitro system is described in which the rat glial RN2 cell line functions as a discriminating host for the JHM virus. Shortly after inoculation, this virus establishes a persistent infection in which there is a cyclical rise and fall in titer with an accompanying cytopathology. Furthermore, this host cell confers a thermal lability which the virus does not demonstrate in the fully permissive host cell, L-2. By comparison, infection of RN2 cells with the prototype MHV3 is aborted immediately. In the persistent infection of RN2 cells with measles virus, Hallé strain, the cell again confers a temperature sensitivity which the virus does not possess when replicating in Vero cells. This appears to be the first instance in which a cloned cell line of glial origin determines the outcome of the infectious process, discriminating in favor of a neurotropic variant which possesses a tropism for the glia in vivo. Systems such as the one described here may now offer a specific screening procedure for selecting, identifying and characterizing the nature of neurotropic viruses.


title: Respiratory syncytial virus outbreak defined by rapid screening in a neonatal intensive care unit

text: Summary Palivizumab is currently licensed for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in infants and children with chronic lung disease, with a history of preterm birth, or with haemodynamically significant congenital heart disease, but its routine use during outbreaks in neonatal intensive care units (NICUs) is not currently recommended. Here we report an outbreak in a NICU detected during a screening trial for RSV infection using a rapid antigen test (Respi-Strip®). Eleven preterm infants in our NICU tested positive for RSV during January 2009. Subsequent testing of the remaining infants in the NICU revealed two additional asymptomatic cases. In addition to precautions against cross-infection, palivizumab prophylaxis was administered to the remaining 37 premature infants. Two days after treatment, RSV was detected in two additional infants who had become symptomatic. To our knowledge this is the largest RSV outbreak in a NICU to be identified at an early stage by rapid testing and effectively controlled by infection control measures and palivizumab prophylaxis.


title: Manifold construction based on local distance invariance

text: This paper presents a distance invariant manifold that preserves the neighborhood relations among data patterns. All patterns have their corresponding cells in the manifold space. The constellation of neighborhood cells closely resembles that of patterns. The manifold is invariant under the translation, rotation and scale of the pattern coordinates. The neighborhood relations among cells are adjusted and improved in each iteration according to the reduction of the distance preservation energy.


title: Effects of In-Person Navigation to Address Family Social Needs on Child Health Care Utilization: A Randomized Clinical Trial

text: IMPORTANCE: While many organizations endorse screening for social risk factors in clinical settings, few studies have examined the health and utilization effects of interventions to address social needs. OBJECTIVE: To compare the acute care utilization effects of a written resources handout vs an in-person navigation service intervention to address social needs. DESIGN, SETTINGS, AND PARTICIPANTS: In this secondary analysis of a randomized clinical trial, 1809 adult caregivers of pediatric patients seen in primary and urgent care clinics of 2 safety-net hospitals in northern California were recruited between October 13, 2013, and August 27, 2015. Each participating family was randomly assigned to an in-person navigator intervention vs active control to address the family’s social needs. Analyses were conducted between February 28, 2018, and September 25, 2019. INTERVENTIONS: Caregivers either received written information about relevant local resources related to social needs (active control) or met with a patient navigator focused on helping them resolve social needs (navigator intervention). After an initial in-person visit, navigation services included telephone, email, and/or in-person follow-up for up to 3 months. MAIN OUTCOME AND MEASURES: Child emergency department visit or hospitalization within 12 months of study enrollment. RESULTS: Among the 1300 caregivers enrolled in the study without missing follow-up data, most spoke English (878 [67.5%]) and were women (1127 [86.7%]), with a mean (SD) age of 33.0 (9.33) years. Most children were aged 0 to 5 years (779 of 1300 [59.9%]), 723 children (55.6%) had Hispanic ethnicity, and 462 children (35.5%) were in excellent health; 840 families (64.6%) were recruited from urgent care. In total, 637 families (49.0%) were randomized to the in-person navigator group and 663 (51.0%) to the active control group. There was no difference in risk of an emergency department visit between the 2 groups. Children enrolled in the in-person navigator group had a decreased risk of hospitalization within 12 months (hazard ratio, 0.59; 05% CI, 0.38-0.94; P = .03), making them 69% less likely to be hospitalized. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial evaluating heath care utilization effects of programs designed to address social needs among families, children enrolled in the navigation group were significantly less likely to be hospitalized after the intervention but equally likely to have an emergency department visit. These findings strengthen our understanding of the effects of addressing social needs in clinical settings as part of a comprehensive strategy to improve health and reduce health care utilization. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01939704


Value and Challenges: Nucleic Acid Amplification Tests for SARS–CoV-2 in Hospitalized COVID-19 Patients


title: Airborne transmission of SARS-CoV-2: the world should face the reality

text: Abstract Hand washing and maintaining social distance are the main measures recommended by the World Health Organization (WHO) to avoid contracting COVID-19. Unfortunately, these measured do not prevent infection by inhalation of small droplets exhaled by an infected person that can travel distance of meters or tens of meters in the air and carry their viral content. Science explains the mechanisms of such transport and there is evidence that this is a significant route of infection in indoor environments. Despite this, no countries or authorities consider airborne spread of COVID-19 in their regulations to prevent infections transmission indoors. It is therefore extremely important, that the national authorities acknowledge the reality that the virus spreads through air, and recommend that adequate control measures be implemented to prevent further spread of the SARS-CoV-2 virus, in particularly removal of the virus-laden droplets from indoor air by ventilation.


Severe acute respiratory syndrome and other emerging severe respiratory viral infections


title: Cyberpsychology research and COVID-19

text: • Research in cyberpsychology is needed during the COVID-19 pandemic. • COVID-19 elicits new challenges for cyrberpsychology research. • Online technologies will be part of the solution to mitigate the crisis.


title: Oral Chemotherapy for Treatment of Lung Cancer

text: The global COVID-19 pandemic has disrupted healthcare delivery, particularly for patients with advanced lung cancer. While certain aspects of care can be safely omitted or delayed, systemic therapy plays an important role in survival and quality of life for patients with advanced lung cancer; limiting access to systemic therapy will compromise cancer-related outcomes. This can be at odds with strategies to mitigate risk of COVID-19 exposure, which include reducing hospital and clinic visits. One important strategy is implementation of oral cancer therapies. Many standard regimens require intravenous infusions but there are specific circumstances where an oral agent could be an acceptable alternative. Integrating oral therapeutics can permit patients to receive effective systemic treatment without the exposure risks associated with frequent infusions. Here, we review currently available oral cytotoxic agents with a potential role in the treatment of lung cancer.


title: The Pandemic and the Role of the Program Director as Gatekeeper

text: Short Summary: Graduation decisions are weighty and sometimes difficult, even under normal circumstances. The novel coronavirus (COVID-19) pandemic has imposed highly abnormal circumstances, leaving the program director with less than the usual amount of data to inform 2020 graduation decisions. Nevertheless, the program director is obligated to the program, the sponsoring institution, the residents/fellows and, most importantly, to the public to graduate only those residents/fellows who are truly prepared to safely and independently practice their specialty.


title: Biothreat Agents and Emerging Infectious Disease in the Emergency Department

text: The challenges faced by the emergency physician with recognizing and treating category A biothreat agents and emerging infectious disease are summarized and reviewed.


title: Purification of turkey coronavirus by Sephacryl size-exclusion chromatography

text: Abstract Sephacryl S-1000 size-exclusion chromatography was used to purify turkey coronavirus (TCoV) from infected turkey embryo. TCoV was propagated in the 22-day-old turkey embryos. Intestines and intestinal contents of infected embryos were harvested and homogenized. After low speed centrifugation, the supernatant was concentrated by ultracentrifugation through a cushion of 30 or 60% sucrose solution, or by ammonium sulfate precipitation. The purification methods included sucrose gradient and Sephacryl S-1000 size-exclusion chromatography. Ultracentrifugation through a cushion of 60% sucrose solution was better than the other two methods for concentration of TCoV from intestinal homogenate. The most effective method for purifying TCoV and removing extraneous materials was size-exclusion chromatography as analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. More spike-rich particles were observed in the sample purified by chromatography than those purified by sucrose gradient as examined by electron microscopy. Differentiation of turkey anti-TCoV antiserum from normal turkey serum was better achieved by ELISA plates coated with TCoV preparation purified by size-exclusion chromatography than that purified by sucrose density gradient. The results indicated that Sephacryl S-1000 chromatography was useful for purification of TCoV.


title: Immune response to SARS‐CoV‐2 and mechanisms of immunopathological changes in COVID‐19

text: As a zoonotic disease that has already spread globally to several million human beings and possibly to domestic and wild animals, eradication of coronavirus disease 2019 (COVID‐19) appears practically impossible. There is a pressing need to improve our understanding of the immunology of this disease to contain the pandemic by developing vaccines and medicines for the prevention and treatment of patients. In this review, we aim to improve our understanding on the immune response and immunopathological changes in patients linked to detoriating clinical conditions such as, cytokine storm, acute respiratory distress syndrome, autopsy findings and changes in acute phase reactants and serum biochemistry in COVID‐19. Similar to many other viral infections, asymptomatic disease is present in a significant but currently unknown fraction of the affected individuals.In the majority of the patients, a one‐week, self‐limiting viral respiratory disease typically occurs, which ends with the development of neutralizing anti‐viral T cell and antibody immunity. The IgM, IgA and IgG type virus‐specific antibodies levels are important measurements to predict population immunity against this disease and whether cross‐reactivity with other coronaviruses is taking place.High viral‐load during the first infection and repeated exposure to virus especially in healthcare workers can be an important factor for severity of disease. It should be noted that many aspects of severe patients are unique to COVID‐19 and are rarely observed in other respiratory viral infections, such as severe lymphopenia and eosinopenia, extensive pneumonia and lung tissue damage, a cytokine storm leading to acute respiratory distress syndrome and multiorgan failure. Lymphopenia causes a defect in antiviral and immune regulatory immunity. At the same time, a cytokine storm starts with extensive activation of cytokine‐secreting cells with innate and adaptive immune mechanisms both of with contribute to a poor prognosis. Elevated levels of acute phase reactants and lymphopenia are early predictors of high disease severity. Prevention of development to severe disease, cytokine storm, acute respiratory distress syndrome and novel approachs to prevent their development will be main routes for future research areas. As we learn to live amidst the virus, understanding the immunology of the disease can assist in containing the pandemic and in developing vaccines and medicines to prevent and treat individual patients.


title: Synthesis, biological evaluation and molecular modeling of a novel series of fused 1,2,3-triazoles as potential anti-coronavirus agents

text: Synthesis and biological evaluation of a novel library of fused 1,2,3-triazole derivatives are described. The in-house developed multicomponent reaction based on commercially available starting materials was applied and broad biological screening against various viruses was performed, showing promising antiviral properties for compounds 14d, 14n, 14q, 18f and 18i against human coronavirus 229E. Further in silico studies identified the key molecular interactions between those compounds and the 3-chymotrypsin-like protease, which is essential to the intracellular replication of the virus, supporting the hypothesis that the protease is the target molecule of the potential antiviral derivatives.


title: Using rapid online surveys to assess perceptions during infectious disease outbreaks: a cross-sectional survey on Covid-19 among the general public in the United States and United Kingdom

text: Background: Given the extensive time needed to conduct a nationally representative household survey and the commonly low response rate in phone surveys, rapid online surveys may be a promising method to assess and track knowledge and perceptions among the general public during fast-moving infectious disease outbreaks. Objective: To apply rapid online surveying to determine knowledge and perceptions of coronavirus disease 2019 (Covid-19) among the general public in the United States (US) and the United Kingdom (UK). Methods: An online questionnaire was administered to 3,000 adults residing in the US and 3,000 adults residing in the UK who had registered with Prolific Academic to participate in online research. Strata by age (18 - 27, 28 - 37, 38 - 47, 48 - 57, or >=58 years), sex (male or female), and ethnicity (White, Black or African American, Asian or Asian Indian, Mixed, or "Other"), and all permutations of these strata, were established. The number of participants who could enrol in each of these strata was calculated to reflect the distribution in the US and UK general population. Enrolment into the survey within the strata was on a first-come, first-served basis. Participants completed the questionnaire between February 23 and March 2 2020. Results: 2,986 and 2,988 adults residing in the US and the UK, respectively, completed the questionnaire. 64.4% (1,924/2,986) of US and 51.5% (1,540/2,988) of UK participants had a tertiary education degree. 67.5% (2,015/2,986) of US participants had a total household income between $20,000 and $99,999, and 74.4% (2,223/2,988) of UK participants had a total household income between GBP15,000 and GBP74,999. US and UK participants' median estimate for the probability of a fatal disease course among those infected with SARS-CoV-2 was 5.0% (IQR: 2.0% - 15.0%) and 3.0% (IQR: 2.0% - 10.0%), respectively. Participants generally had good knowledge of the main mode of disease transmission and common symptoms of Covid-19. However, a substantial proportion of participants had misconceptions about how to prevent an infection and the recommended care-seeking behavior. For instance, 37.8% (95% CI: 36.1% - 39.6%) of US and 29.7% (95% CI: 28.1% - 31.4%) of UK participants thought that wearing a common surgical mask was 'highly effective' in protecting them from acquiring Covid-19. 25.6% (95% CI: 24.1% - 27.2%) of US and 29.6% (95% CI: 28.0% - 31.3%) of UK participants thought it prudent to refrain from eating at Chinese restaurants. Around half (53.8% [95% CI: 52.1% - 55.6%] of US and 39.1% [95% CI: 37.4% - 40.9%] of UK participants) thought that children were at an especially high risk of death when infected with SARS-CoV-2. Conclusions: The distribution of participants by total household income and education followed approximately that of the general population. The findings from this online survey could guide information campaigns by public health authorities, clinicians, and the media. More broadly, rapid online surveys could be an important tool in tracking the public's knowledge and misperceptions during rapidly moving infectious disease outbreaks.


title: Evaluation of the user seal check on gross leakage detection of 3 different designs of N95 filtering facepiece respirators

text: BACKGROUND: The use of N95 respirators prevents spread of respiratory infectious agents, but leakage hampers its protection. Manufacturers recommend a user seal check to identify on-site gross leakage. However, no empirical evidence is provided. Therefore, this study aims to examine validity of a user seal check on gross leakage detection in commonly used types of N95 respirators. METHODS: A convenience sample of 638 nursing students was recruited. On the wearing of 3 different designs of N95 respirators, namely 3M-1860s, 3M-1862, and Kimberly-Clark 46827, the standardized user seal check procedure was carried out to identify gross leakage. Repeated testing of leakage was followed by the use of a quantitative fit testing (QNFT) device in performing normal breathing and deep breathing exercises. Sensitivity, specificity, predictive values, and likelihood ratios were calculated accordingly. RESULTS: As indicated by QNFT, prevalence of actual gross leakage was 31.0%-39.2% with the 3M respirators and 65.4%-65.8% with the Kimberly-Clark respirator. Sensitivity and specificity of the user seal check for identifying actual gross leakage were approximately 27.7% and 75.5% for 3M-1860s, 22.1% and 80.5% for 3M-1862, and 26.9% and 80.2% for Kimberly-Clark 46827, respectively. Likelihood ratios were close to 1 (range, 0.89-1.51) for all types of respirators. CONCLUSIONS: The results did not support user seal checks in detecting any actual gross leakage in the donning of N95 respirators. However, such a check might alert health care workers that donning a tight-fitting respirator should be performed carefully.


title: Colorimetric viral detection based on sialic acid stabilized gold nanoparticles

text: Sialic acid reduced and stabilized gold nanoparticles (d = 20.1 ± 1.8 nm) were synthesized by a simple one-pot, green method without chemically modifying sialic acid for colorimetric detection of influenza virus. The gold nanoparticles showed target-specific aggregation with viral particles via hemagglutinin-sialic acid binding. A linear correlation was observed between the change in optical density and dilution of chemically inactivated influenza B/Victoria and influenza B/Yamagata. Virus dilution (hemagglutinination assay titer, 512) of 0.156 vol% was readily detected. The upper limit of the linearity can be extended with the use of more sialic acid-gold nanoparticles.


title: A novel mechanism for immune regulation after human lung transplantation

text: Abstract Objective Lung transplantation is therapeutic for end-stage lung disease, but survival is limited due to bronchiolitis obliterans syndrome and restrictive chronic lung allograft dysfunction. We sought a common denominator in lung transplant recipients, analyzing risk factors that trigger immune responses that lead to bronchiolitis obliterans syndrome. Methods We collected blood from patients who underwent lung transplant at our institution. Exosomes were isolated from the sera of recipients with risk factors for chronic rejection and from stable recipients. Exosomes were analyzed with western blot, using antibodies to lung self-antigens K alpha 1 tubulin and collagen-V, costimulatory molecules (costimulatory molecule 80, costimulatory molecule 86), transcription factors (nuclear factor kappa-light-chain-enhancer of activated B cells, hypoxia-inducible factor 1α, Class II Major Histocompatibility Complex Transactivator), and 20S proteasome. Results Of the 90 patients included, we identified 5 with grade 3 primary graft dysfunction, 5 without, 15 with respiratory viral infection, 10 with acute rejection, 10 with donor-specific antibodies (DSA), 5 without DSA, and 10 who were stable for exosome isolation. Recipients with grade 3 primary graft dysfunction, respiratory viral infection, acute rejection, and DSA had exosomes containing self-antigens; exosomes from stable recipients did not. Exosomes from recipients with grade 3 primary graft dysfunction, acute rejection, and DSA also demonstrated costimulatory molecule 80, costimulatory molecule 86, major histocompatibility complex class II, transcription factor, and 20S proteasome. Conclusions Transplanted lungs with grade 3 primary graft dysfunction, symptomatic respiratory viral infection, acute rejection, and immune responses induce exosomes that contain self-antigens, costimulatory molecules, major histocompatibility complex class II, transcription factors, and 20S proteasome. Release of circulating exosomes post-transplant from the aforementioned stress-inducing insults augment immunity and may play an important role in the pathogenesis of bronchiolitis obliterans syndrome.


title: Cellulose–polymer–Ag nanocomposite fibers for antibacterial fabrics/skin scaffolds

text: Abstract Natural carbohydrates (polysaccharides): gum acacia (GA) and gaur gum (GG) were employed in dilute solutions: 0.3%, 0.5% and 0.7% (w/v), as effective reductants for the green synthesis of silver nanoparticles (AgNPs) from AgNO3. The formed AgNPs were impregnated into cellulose fibers after confirming their formation by utilizing ultraviolet–visible (UV–vis) spectral studies, Fourier transforms infrared (FTIR) and transmission electron microscopy (TEM). The surface morphology of the developed cellulose–silver nanocomposite fibers (CSNCFs) were examined with scanning electron microscope-energy dispersive spectroscopy (SEM-EDS). The thermal stability and mechanical properties of the CSNCFs were found to be better than cellulose fibers alone. The antibacterial activity of the nanocomposites was studied by inhibition zone method against Escherichia coli, which suggested that the developed CSNCFs can function effectively as anti-microbial agents. Hence, the developed CSNCFs can effectively used for tissue scaffolding.


title: Protection conferred by a recombinant Marek’s disease virus that expresses the spike protein from infectious bronchitis virus in specific pathogen-free chicken

text: BACKGROUND: In many countries, the predominant field isolates of infectious bronchitis virus (IBV) have been classified as QX-like strains since 1996. However, no commercial vaccines that are specific for this type of IBV are currently available. Therefore, there is an urgent need to develop novel vaccines that prevent QX-like IBV infection. RESULTS: A recombinant Marek’s disease virus (MDV), rMDV-S1, that expresses the S1 subunit of the spike (S) protein from the QX-like infectious bronchitis virus (IBV) was constructed by inserting the IBV S1 gene into the genome of the CVI988/Rispens strain of MDV. Specific pathogen-free (SPF) chickens that were vaccinated with rMDV-S1 were protected when challenged with the QX-like IBV. They were observed to have mild clinical signs of disease, a short virus-shedding period and low mortality. Additionally, the rMDV-S1 conferred full protection to chickens against virulent MDV, as did the CVI988/Rispens strain. CONCLUSIONS: Our results demonstrate that rMDV-S1 is an effective and promising recombinant vaccine for the prevention of QX-like IBV infection.


title: Design, construction and validation of a nose‐only inhalation exposure system to measure infectivity of filtered bioaerosols in mice

text: AIMS: The aim of this project was to validate a method to deliver a reproducible, selected dose of infective bioaerosol through a respiratory protective technology to an animal that exhibits a proportional clinical response. METHODS AND RESULTS: The Controlled Aerosol Test System (CATS) was designed to generate and condition a viable infective aerosol, pass it through a treatment technology and thence to the breathing zone of a mouse constrained in a Nose‐Only Inhalation Exposure System (NOIES). A scanning mobility particle sizer and impingers at sampling ports were used to show that viability is preserved and particle size distribution (PSD) is acceptably uniform throughout the open CATS, including the 12 ports of the NOIES, and that a particle filter used caused the expected attenuation of particle counts. CONCLUSIONS: Controlled Aerosol Test System delivers uniformly to mice constrained in the NOIES a selectable dose of viral bioaerosol whose PSD and viable counts remain consistent for an hour. SIGNIFICANCE AND IMPACT OF THE STUDY: This study's characterization of CATS provides a new test system in which a susceptible small‐animal model can be used as the detector in a quantitative method to evaluate the ability of respiratory protective technologies to attenuate the infectivity of an inspired pathogenic aerosol. This provides a major improvement over the use of viable bioaerosol collectors (e.g. impactors and impingers), which provide data that are difficult to relate to the attenuation of pathogenicity.


title: Selection of and recombination between minor variants lead to the adaptation of an avian coronavirus to primate cells

text: Abstract An interesting question posed by the current evidence that severe acute respiratory syndrome coronavirus may be originated from an animal coronavirus is how such an animal coronavirus breaks the host species barrier and becomes zoonotic. In this report, we study the chronological order of genotypic changes in the spike protein of avian coronavirus infectious bronchitis virus (IBV) during its adaptation to a primate cell line. Adaptation of the Beaudette strain of IBV from chicken embryo to Vero cells showed the accumulation of 49 amino acid mutations. Among them, 26 (53.06%) substitutions were located in the S protein. Sequencing analysis and comparison of the S gene demonstrated that the majority of the mutations were accumulated and fixed at passage 7 on Vero cells and minor variants were isolated in several passages. Evidence present suggests that the dominant Vero cell-adapted IBV strain may be derived from the chicken embryo passages by selection of and potential recombination between the minor variants. This may explain why adaptation is a rapid process and the dominant strain, once adapted to a new host cell, becomes relatively stable.


title: Sustainable Diabetes Care Services during COVID-19 Pandemic

text: Abstract Introduction The COVID-19 pandemic creates a challenge in the provision of care for patients with diabetes. Furthermore, those with uncontrolled diabetes are at a higher risk for complications due to COVID-19. The purpose of this study is to find an innovative method to sustain effective diabetes care services amidst the COVID-19 pandemic. Methods Outpatient diabetes care was successfully transformed from traditional face-to-face encounters in the clinic to an online telemedicine service. Results 1,972 patients were encountered over a 4-week study period during which we had a low proportion of unreached patients (4%). Some patients were still seen in person because they came as walk-in visits or insisted to be seen in person. Conclusion Telemedicine has become an essential healthcare service and could be augmented by the use of technology like web-based applications and communication via transfer of data from patients’ glucometer, insulin pumps, or sensors. Diabetes care can be transitioned to telemedicine effectively and would be successful in reaching more patients than by traditional face-to-face visits. This model of care is time consuming and unfortunately does not reduce the need for medical staff.


title: Pernio-like skin lesions associated with COVID-19: a case series of 318 patients from 8 countries

text: Abstract Background Increasing evidence suggests pernio-like lesions are cutaneous manifestations of COVID-19. Objective To describe clinical and pathologic findings of pernio-like lesions in confirmed or suspected COVID-19 cases. Methods An international dermatology registry was circulated to healthcare providers worldwide through the American Academy of Dermatology (AAD), International League of Dermatologic Societies (ILDS), and other organizations. Results We documented 505 patients with dermatologic manifestations associated with COVID-19, including 318 (63%) with pernio-like lesions. Patients with pernio-like lesions were generally young and healthy, with relatively mild COVID-19. Of 318 cases confirmed or suspected as COVID-19 by providers, twenty-three cases (7%) were laboratory-confirmed COVID-19 positive, and 20 others (6%) were close contacts of confirmed COVID-19 cases. Given current testing criteria, many patients lacked COVID-19 testing access. For 55% of patients, pernio-like lesions were their only symptom. In patients with other COVID-19 symptoms, pernio-like lesions typically appeared after other symptoms. Pernio-like lesions lasted a median of 14 days (IQR 10-21). Limitations A case series cannot estimate population level incidence or prevalence. Additionally, there may be confirmation bias in reporting. We cannot exclude an epiphenomenon. Conclusions Pernio-like skin changes of the feet and hands, without another explanation, may suggest COVID-19 infection and should prompt confirmatory testing.


title: Naïve Human Antibody Libraries for Infectious Diseases

text: Many countries are facing an uphill battle in combating the spread of infectious diseases. The constant evolution of microorganisms magnifies the problem as it facilitates the re-emergence of old infectious diseases as well as promote the introduction of new and more deadly variants. Evidently, infectious diseases have contributed to an alarming rate of mortality worldwide making it a growing concern. Historically, antibodies have been used successfully to prevent and treat infectious diseases since the nineteenth century using antisera collected from immunized animals. The inherent ability of antibodies to trigger effector mechanisms aids the immune system to fight off pathogens that invades the host. Immune libraries have always been an important source of antibodies for infectious diseases due to the skewed repertoire generated post infection. Even so, the role and ability of naïve antibody libraries should not be underestimated. The naïve repertoire has its own unique advantages in generating antibodies against target antigens. This chapter will highlight the concept, advantages and application of human naïve libraries as a source to isolate antibodies against infectious disease target antigens.


title: Novel Molecular Type of Clostridium difficile in Neonatal Pigs, Western Australia

text: Clostridium difficile causes neonatal enteritis in piglets; strains of PCR ribotype 078 are most commonly identified. We investigated C. difficile prevalence in piglets in Australia and isolated a novel strain with a unique pathogenicity locus. In a mouse infection model, this strain produced more weight loss than did a ribotype 078 strain.


title: Single-Family Room Design in the Neonatal Intensive Care Unit—Challenges and Opportunities

text: The trend toward single-family room (SFR) design in the neonatal intensive care unit (NICU) has been driven by a growing understanding of the developmental needs of preterm infants, a desire to provide environments that support and encourage family participation, and infection control considerations. SFR design offers many potential benefits, but also requires substantial change in the NICU culture, as well as additional space and technology when compared to an open ward. The advantages and drawbacks of the SFR design are reviewed, and strategies are offered to assist those who are considering construction or renovation of an NICU.


title: Modeling respiratory illnesses with change point: A lesson from the SARS epidemic in Hong Kong

text: Abstract It is generally agreed that respiratory disease is closely related to ambient air quality and weather conditions. Besides, hygiene related factors such as the public health measures by the government and possible personal awareness in the community can also affect the spread of infectious respiratory diseases. However, there is no quantitative support for this conclusion, because of lack of quality data. The severe acute respiratory syndrome (or SARS) outbreak in 2003 triggered strict public health measures and personal awareness in the prevention of infectious respiratory diseases, providing us an opportunity to quantify the impact of hygiene related factors in the spread of the disease. In this paper, we model the number of the respiratory illnesses by a semiparametric model which models the environmental and weather impacts using a multiple index model and the impact of other public health measures and possible personal awareness using a growth curve with jump. Using data from Hong Kong, we found that public health measures contributed to about 39% of reduction in the number of respiratory illnesses during the SARS period. However, the impact of hygienically related factors eventually fades as time passes. The results provide indirect quantitative support to the usefulness of governmental campaigns to arouse the awareness of the public in staying away from transmission of respiratory diseases during the full outbreak of the disease. The results also show the fast fading of alertness of Hong Kong people towards the epidemic. Furthermore, our model also offers a way to model the impacts of environmental factors on respiratory diseases, when the data contains the effect of human intervention, by introducing the change point and growth curve to remove such an effect.


title: Oral disorders of exotic rodents

text: Our dental knowledge of rodents is still patchy but their increasing popularity and advances in technology allow us to make good strides toward better understanding. Cutting incisors with nail clippers and treating incisor problems without examining cheek teeth is no longer acceptable. Good practice dictates that a thorough examination is performed, a diagnosis is made, and treatment is planned and executed appropriately. Dentistry is expanding at a tremendous rate; the next few years should provide plenty of opportunities to solve most of the remaining problems with dental disease in rodents.


title: Dengue conundrums

text: Abstract Dengue virus is the most common arboviral infection of humans in the tropical and subtropical regions of the world. This review briefly describes some of the challenges it presents. Dengue is an emerging disease; it is increasing in geographical distribution and severity, despite being significantly underreported. The World Health Organization case definition for the generally more severe manifestation of infection, dengue haemorrhagic fever (DHF), is controversial. The name DHF is something of a misnomer as the disease infrequently results in frank haemorrhage; the hallmark of DHF is actually plasma leakage. The existence of four closely related dengue virus serotypes contributes to difficulties in diagnosis and to original antigenic sin in the serological response to infection. The existence of multiple serotypes can result in more severe disease upon a second infection and complicates vaccine development. Nevertheless, a safe and effective vaccine is the greatest prospect for stemming the tide of dengue.


Using the Systems Engineering Initiative for Patient Safety (SEIPS) model to describe critical care nursing during the SARS‐CoV‐2 pandemic (2020)


title: Psoriasis health care in the time of the coronavirus pandemic: insights from dedicated centers in sardinia (Italy)

text: Psoriasis is a major chronic inflammatory skin disease, affecting about 3% of the population in Italy, whose management require experienced specialists in order to guarantee high‐quality standards of care. The pandemic coronavirus (2019‐nCoV; COVID‐19) has changed the approach to all patients requiring close contact during a visit, including dermatologic consultations. In Italy, true outbreak begun in Lombardy, by February 21, 2020 with exponential contagion, surpassing China in the number of deaths.


title: Prevalence of serum antibodies against Bartonella species in the serum of cats with or without uveitis

text: Bartonella henselae has been implicated as a causative agent of chronic uveitis in people and in some cats. The objective of this study was to determine whether Bartonella species seroprevalence or titer magnitude varies among cats with uveitis, cats without ocular diseases recorded and healthy cats, while controlling for age and risk of flea exposure based on state of residence. There was no difference in seroprevalence rates or titer magnitude between cats with uveitis and cats with non-ocular diseases. Healthy cats were more likely to be seropositive for Bartonella species than cats with uveitis. The median Bartonella species titer was 1:64 for all groups, although healthy cats were more likely to have higher titers than cats with uveitis and cats with non-ocular disease. The results suggest that serum antibody tests alone cannot be used to document clinical uveitis associated with Bartonella species infection.


title: Crazy paving pattern as a rare radiological manifestation of peripheral T-cell lymphoma (PTCL) with lung involvement: A case report

text: We report on a 70-year old woman with dyspnea, systemic lymphadenopathy and abnormal chest computed tomography (CT) findings. A complete laboratory testing as well as mediastinal tissue sampling via Endobronchial Ultrasound (EBUS)-guided Transbronchial Needle Biopsy (TBNB) did not reveal a definite diagnosis. After experiencing acute respiratory failure which led to intensive care unit, the patient underwent a cervical lymph node biopsy which revealed peripheral T-cell lymphoma not otherwise specified (PTCL-NOS). A CT-guided trans-thoracic lung biopsy was performed that showed involvement of the lung parenchyma in the context of PTCL-NOS. Lung involvement is a rare extra-nodal manifestation of PTCL. The imaging patterns of this lymphoma have not been well described. We conclude that the finding of crazy paving pattern is a rare manifestation of this disease. In patients with pre-existing lymphoma, lung involvement should be included in the differential due to high pre-test probability.


title: Are you surgically current? Lessons from aviation for returning to non-urgent surgery following COVID-19

text: The COVID-19 crisis has caused many issues across healthcare. In surgery, many operations have been cancelled with some surgeons losing their regular operating lists. During this time, technical expertise and decision making can deteriorate. In aviation after a prolonged period of absence from flying, this deficit in keeping skills and thinking up to date is known as being “out of currency” or “not current”. Although aviation and healthcare cannot be compared, numerous human factors concepts are applicable to both. In this article, we explore the likely impact of potentially prolonged absences in operating on surgical skills and psyche, and introduce the concept of a Surgical Skills Currency Barometer. We also discuss a “task-o-meter” thought experiment, and suggest practices which could be adopted to help protect surgeon workload from exceeding surgical capability when returning to operating following a period of prolonged absence.


title: Replicating and Non-replicating Viral Vectors for Vaccine Development

text: Viral vectors provide a convenient means to deliver vaccine antigens to select target cells or tissues. A broad spectrum of replicating and non-replicating vectors is available. An appropriate choice for select applications will depend on the biology of the infectious agent targeted, as well as factors such as whether the vaccine is intended to prevent infection or boost immunity in already infected individuals, prior exposure of the target population to the vector, safety, and the number and size of gene inserts needed. Here several viral vectors under development as HIV/AIDS vaccines are reviewed. A vaccine strategy based on initial priming with a replicating vector to enlist the innate immune system, target mucosal inductive sites, and prime both cellular and humoral systemic and mucosal immune responses is proposed. Subsequently, boosting with a replicating or non-replicating vector and/or protein subunits could lead to induction of necessary levels of protective immunity.


title: Dual roles of calpain in facilitating Coxsackievirus B3 replication and prompting inflammation in acute myocarditis

text: Abstract Background Viral myocarditis (VMC) treatment has long been lacking of effective methods. Our former studies indicated roles of calpain in VMC pathogenesis. This study aimed at verifying the potential of calpain in Coxsackievirus B3 (CVB3)-induced myocarditis treatment. Methods A transgenic mouse overexpressing the endogenous calpain inhibitor, calpastatin, was introduced in the study. VMC mouse model was established via intraperitoneal injection of CVB3 in transgenic and wild mouse respectively. Myocardial injury was assayed histologically (HE staining and pathology grading) and serologically (myocardial damage markers of CK-MB and cTnI). CVB3 replication was observed in vivo and in vitro via the capsid protein VP1 detection or virus titration. Inflammation/fibrotic factors of MPO, perforin, IFNγ, IL17, Smad3 and MMP2 were evaluated using western blot or immunohistology stain. Role of calpain in regulating fibroblast migration was studied in scratch assays. Results Calpastatin overexpression ameliorated myocardial injury induced by CVB3 infection significantly in transgenic mouse indicated by reduced peripheral CK-MB and cTnI levels and improved histology injury. Comparing with CVB3-infected wild type mouse, the transgenic mouse heart tissue carried lower virus load. The inflammation factors of MPO, perforin, IFNγ and IL17 were down-regulated accompanied with fibrotic agents of Smad3 and MMP2 inhibition. And calpain participated in the migration of fibroblasts in vitro, which further proves its role in regulating fibrosis. Conclusion Calpain plays dual roles of facilitating CVB3 replication and inflammation promotion. Calpain inhibition in CVB3-induced myocarditis showed significant treatment effect. Calpain might be a novel target for VMC treatment in clinical practices.


title: Sialic acid involves in the interaction between ovomucin and hemagglutinin and influences the antiviral activity of ovomucin

text: Abstract Ovomucin (OVM) plays an important role in inhibiting infection of various pathogens. However, this bioactivity mechanism is not much known. Here, the role of sialic acid in OVM anti-virus activity has been studied by ELISA with lectin or ligand. Structural changes of OVM after removing sialic acid were analyzed by circular dichroism and fluorescence spectroscopy. OVM could be binding to the hemagglutinin (HA) of avian influenza viruses H5N1 and H1N1, this binding was specific and required the involvement of sialic acid. When sialic acid was removed, the binding was significantly reduced 71.5% and 64.35%, respectively. Therefore, sialic acid was proved as a recognition site which avian influenza virus bound to. Meanwhile, the endogenous fluorescence and surface hydrophobicity of OVM removing sialic acid were increased and the secondary structure tended to shift to random coil. This indicated that OVM molecules were in an unfolded state and spatial conformation disorder raising weakly. Remarkably, free sialic acid strongly promoted OVM binding to HA and thereby enhanced the interaction. It may contribute to the inhibition of host cell infection, agglutinate viruses. This study can be extended to the deepening of passive immunization field.


title: Co-infection of classic swine H1N1 influenza virus in pigs persistently infected with porcine rubulavirus

text: Abstract Porcine rubulavirus (PorPV) and swine influenza virus infection causes respiratory disease in pigs. PorPV persistent infection could facilitate the establishment of secondary infections. The aim of this study was to analyse the pathogenicity of classic swine H1N1 influenza virus (swH1N1) in growing pigs persistently infected with porcine rubulavirus. Conventional six-week-old pigs were intranasally inoculated with PorPV, swH1N1, or PorPV/swH1N1. A mock-infected group was included. The co-infection with swH1N1 was at 44 days post-infection (DPI), right after clinical signs of PorPV infection had stopped. The pigs of the co-infection group presented an increase of clinical signs compared to the simple infection groups. In all infected groups, the most recurrent lung lesion was hyperplasia of the bronchiolar-associated lymphoid tissue and interstitial pneumonia. By means of immunohistochemical evaluation it was possible to demonstrate the presence of the two viral agents infecting simultaneously the bronchiolar epithelium. Viral excretion of PorPV in nasal and oral fluid was recorded at 28 and 52 DPI, respectively. PorPV persisted in several samples from respiratory tissues (RT), secondary lymphoid organs (SLO), and bronchoalveolar lavage fluid (BALF). For swH1N1, the viral excretion in nasal fluids was significantly higher in single-infected swH1N1 pigs than in the co-infected group. However, the co-infection group exhibited an increase in the presence of swH1N1 in RT, SLO, and BALF at two days after co-infection. In conclusion, the results obtained confirm an increase in the clinical signs of infection, and PorPV was observed to impact the spread of swH1N1 in analysed tissues in the early stage of co-infection, although viral shedding was not enhanced. In the present study, the interaction of swH1N1 infection is demonstrated in pigs persistently infected with PorPV.


title: Analyzing Cytotoxic and Apoptogenic Properties of Scutellaria litwinowii Root Extract on Cancer Cell Lines

text: The Scutellaria species (Lamiaceae) is used as a source of flavonoids to treat a variety of diseases in traditional medicine. In spite of many reports about the cytotoxic and antitumor effects of some species of this genus, anticancer researches on one of the Iranian species S. litwinowii have not yet been conducted. The cytotoxic properties of total methanol extract of S. litwinowii and its fractions were investigated on different cancer cell lines including AGS, HeLa, MCF-7, PC12 and NIH 3T3. Meanwhile, the role of apoptosis in this toxicity was explored. The cells were cultured in DMEM medium and incubated with different concentrations of herb plant extracts. Cell viability was quantitated by MTT assay. Apoptotic cells were determined using propidium iodide staining of DNA fragmentation by flow cytometry (sub-G1 peak). Scutellaria litwinowii inhibited the growth of malignant cells in a dose-dependent manner. Among solvent fractions of S. litwinowii, the methylene chloride fraction was found to be more toxic compared to other fractions. The IC(50) values of this fraction against AGS, HeLa, MCF-7 and PC12 cell lines after 24 h were determined, 121.2 ± 3.1, 40.9 ± 2.5, 115.9 ± 3.5 and 64.5 ± 3.4 μg/ml, respectively. Scutellaria litwinowii induced a sub-G1 peak in the flow cytometry histogram of treated cells compared to control cells indicating that apoptotic cell death is involved in S. litwinowii toxicity. Scutellaria litwinowii exerts cytotoxic and proapototic effects in a variety of malignant cell lines and could be considered as a potential chemotherapeutic agent in cancer treatment.


title: “Conflating Culture With COVID-19: Xenophobic Repercussions of a Global Pandemic”

text: Abstract This commentary aimed to deconstruct xenophobia and its worldwide impact, particularly on people of Asian descent, amid the global COVID-19 pandemic. The commentary begins with an overview of COVID-19’s impact on the United States economy and educational landscape, continues with a discussion about the global history of pandemic-prompted xenophobia and its relationship to sensationalized media discourse, and concludes with recommendations to reconsider various aspects of intercultural communication in relation to public health issues.


The triage dilemma: opening Pandora's box... ever so slowly


title: High-level expression and purification of soluble recombinant FGF21 protein by SUMO fusion in Escherichia coli

text: BACKGROUND: Fibroblast growth factor 21 (FGF21) is a promising drug candidate to combat metabolic diseases. However, high-level expression and purification of recombinant FGF21 (rFGF21) in Escherichia coli (E. coli) is difficult because rFGF21 forms inclusion bodies in the bacteria making it difficult to purify and obtain high concentrations of bioactive rFGF21. To overcome this problem, we fused the FGF21 with SUMO (Small ubiquitin-related modifier) by polymerase chain reaction (PCR), and expressed the fused gene in E. coli BL21(DE3). RESULTS: By inducing with IPTG, SUMO-FGF21 was expressed at a high level. Its concentration reached 30% of total protein, and exceeded 95% of all soluble proteins. The fused protein was purified by DEAE sepharose FF and Ni-NTA affinity chromatography. Once cleaved by the SUMO protease, the purity of rFGF21 by high performance liquid chromatography (HPLC) was shown to be higher than 96% with low endotoxin level (<1.0 EU/ml). The results of in vivo animal experiments showed that rFGF21 produced by using this method, could decrease the concentration of plasma glucose in diabetic rats by streptozotocin (STZ) injection. CONCLUSIONS: This study demonstrated that SUMO, when fused with FGF21, was able to promote its soluble expression of the latter in E. coli, making it more convenient to purify rFGF21 than previously. This may be a better method to produce rFGF21 for pharmaceutical research and development.


Neprilysin inhibitor–angiotensin II receptor blocker combination (sacubitril/valsartan): rationale for adoption in SARS-CoV-2 patients


title: Increasing Host Cellular Receptor—Angiotensin-Converting Enzyme 2 (ACE2) Expression by Coronavirus may Facilitate 2019-nCoV Infection

text: The ongoing outbreak of a new coronavirus (2019-nCoV) causes an epidemic of acute respiratory syndrome in humans. 2019-nCoV rapidly spread to national regions and multiple other countries, thus, pose a serious threat to public health. Recent studies show that spike (S) proteins of 2019-nCoV and SARS-CoV may use the same host cell receptor called angiotensin-converting enzyme 2 (ACE2) for entering into host cells. The affinity between ACE2 and 2019-nCoV S is much higher than ACE2 binding to SARS-CoV S protein, explaining that why 2019-nCoV seems to be more readily transmitted from the human to human. Here, we reported that ACE2 can be significantly upregulated after infection of various viruses including SARS-CoV and MERS-CoV. Basing on findings here, we propose that coronavirus infection can positively induce its cellular entry receptor to accelerate their replication and spread, thus drugs targeting ACE2 expression may be prepared for the future emerging infectious diseases caused by this cluster of viruses.


title: A comparative study of the etiology of adult upper and lower respiratory tract infections in the community

text: Abstract Lower respiratory tract infection and upper respiratory tract infection (URTI) are very common, but the etiology is not diagnosed in routine practice. The objective of this study was to determine and compare the frequency distribution of the various infectious etiologies for these diseases. One hundred seventy five adults in the community with febrile LRTI and 75 with febrile URTI were included in a purely serologically based prospective study. Paired sera were obtained for each of the patients and were tested by EIA or immunofluorescence methods to identify 14 different pathogens. Only a significant change in antibody titers between the paired sera was considered diagnostic. At least one infectious etiology was identified in 167 patients (67%). In the LRTI group, infection with at least one of 7 respiratory viruses was found in 88 patients (50%). One of the atypical pathogens was found in 40 patients (23%), of these Legionella spp. in 19 (11%) and Mycoplasma pneumoniae in 18 (10%). A bacterial etiology was found in 19 patients (11%), of these Streptococcus pneumoniae in 8 (5%) and β-hemolytic streptococci group A in 5 (3%). The frequency distribution of etiologies in the URTI group was not significantly different from the LRTI group, except for M. pneumoniae that was identified in only one patient with URTI (p = 0.015). More than one etiologic agent was found in 42 (17%) of the patients. LRTI is caused by a broad spectrum of etiologies, with respiratory viruses predominating and a moderate, but significant, prevalence of atypical pathogens. The frequency distribution of etiologies for URTI is similar to LRTI. In a significant proportion of patients with URTI and LRTI there is serologic evidence of infection with more than one pathogen. The justification and benefit of distinguishing between URTI and LRTI in routine clinical work is doubtful. When a decision is reached to treat RTI patients with an antibiotic, it is logical to use a macrolide or tetracycline.


title: Spatial epidemiology of networked metapopulation: An overview

text: An emerging disease is one infectious epidemic caused by a newly transmissible pathogen, which has either appeared for the first time or already existed in human populations, having the capacity to increase rapidly in incidence as well as geographic range. Adapting to human immune system, emerging diseases may trigger large-scale pandemic spreading, such as the transnational spreading of SARS, the global outbreak of A(H1N1), and the recent potential invasion of avian influenza A(H7N9). To study the dynamics mediating the transmission of emerging diseases, spatial epidemiology of networked metapopulation provides a valuable modeling framework, which takes spatially distributed factors into consideration. This review elaborates the latest progresses on the spatial metapopulation dynamics, discusses empirical and theoretical findings that verify the validity of networked metapopulations, and the application in evaluating the effectiveness of disease intervention strategies as well.