title: Plasmonics-Based Detection of Virus Using Sialic Acid Functionalized Gold Nanoparticles

text: Biosensor for the detection of virus was developed by utilizing plasmonic peak shift phenomenon of the gold nanoparticles and viral infection mechanism of hemagglutinin on virus and sialic acid on animal cells. The plasmonic peak of the colloidal gold nanoparticles changes with the aggregation of the particles due to the plasmonic interaction between nearby particles and the color of the colloidal nanoparticle solution changes from wine red to purple. Sialic acid reduced and stabilized colloidal gold nanoparticle aggregation is induced by the addition of viral particles in the solution due to the hemagglutinin-sialic acid interaction. In this work, 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. 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 virus species. The detection limit of the virus dilution (hemagglutinination assay titer, 512) was shown to be 0.156 vol% and the upper limit of the linearity can be extended with the use of more sialic acid-gold nanoparticles.


title: Magnesium and vitamin C supplementation attenuates steroid-associated osteonecrosis in a rat model

text: Abstract Magnesium (Mg)-based biometal attracts clinical applications due to its biodegradability and beneficial biological effects on tissue regeneration, especially in orthopaedics, yet the underlying anabolic mechanisms in relevant clinical disorders are lacking. The present study investigated the effect of magnesium (Mg) and vitamin C (VC) supplementation for preventing steroid-associated osteonecrosis (SAON) in a rat experimental model. In SAON rats, 50 mg/kg Mg, or 100 mg/kg VC, or combination, or water control was orally supplemented daily for 2 or 6 weeks respectively. Osteonecrosis was evaluated by histology. Serum Mg, VC, and bone turnover markers were measured. Microfil-perfused samples prepared for angiography and trabecular architecture were evaluated by micro-CT. Primary bone marrow cells were isolated from each group to evaluate their potentials in osteoblastogenesis and osteoclastogenesis. The mechanisms were tested in vitro. Histological evaluation showed SAON lesions in steroid treated groups. Mg and VC supplementation synergistically reduced the apoptosis of osteocytes and osteoclast number, and increased osteoblast surface. VC supplementation significantly increased the bone formation marker PINP, and the combination significantly decreased the bone resorption marker CTX. TNFα expression and oxidative injury were decreased in bone marrow in Mg/VC/combination group. Mg significantly increased the blood perfusion in proximal tibia and decreased the leakage particles in distal tibia 2 weeks after SAON induction. VC significantly elevated the osteoblast differentiation potential of marrow cells and improved the trabecular architecture. The combination supplementation significantly inhibited osteoclast differentiation potential of marrow cells. In vitro study showed promoting osteoblast differentiation effect of VC, and anti-inflammation and promoting angiogenesis effect of Mg with underlying mechanisms. Mg and VC supplementation could synergistically alleviate SAON in rats, indicating great translational potentials of metallic minerals for preventing SAON.


title: Serotype, antigenicity, and pathogenicity of a naturally recombinant TW I genotype infectious bronchitis coronavirus in China

text: Abstract Since 2009, strains of the naturally recombinant TW I genotype of infectious bronchitis virus (IBV) have caused considerable damage to the Chinese poultry industry. To better understand the antigenicity and pathogenesis of this genotype, the characteristics of the ck/CH/LDL/140520 strain were compared to those of four commercial IB vaccine strains that are used commonly in China, as well as four attenuated viruses that represent two types of IBV strains, which are believed to have originated in China and are the predominant IBV types circulating in chicken flocks in China and many other parts of the world. The results showed that all eight strains were genetically and serotypically different from the strain ck/CH/LDL/140520. Furthermore, neither the vaccine strains nor the attenuated viruses could provide complete respiratory protection of chickens against a challenge with the ck/CH/LDL/140520 strain, indicating that it is necessary to develop new live vaccines or to evaluate the use of established vaccines in combination to control naturally recombinant TW I-type IBV strains in the future. Our results showed that strain ck/CH/LDL/140520 is very pathogenic, and that it is able to cause cystic oviducts in a high percentage of birds, as well as mortality due to nephritis and respiratory distress with complete tracheal ciliostasis, especially in chickens infected at 1day of age.


title: Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period

text: It is urgent to understand the future of severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) transmission. We used estimates of seasonality, immunity, and cross-immunity for betacoronaviruses OC43 and HKU1 from time series data from the USA to inform a model of SARS-CoV-2 transmission. We projected that recurrent wintertime outbreaks of SARS-CoV-2 will probably occur after the initial, most severe pandemic wave. Absent other interventions, a key metric for the success of social distancing is whether critical care capacities are exceeded. To avoid this, prolonged or intermittent social distancing may be necessary into 2022. Additional interventions, including expanded critical care capacity and an effective therapeutic, would improve the success of intermittent distancing and hasten the acquisition of herd immunity. Longitudinal serological studies are urgently needed to determine the extent and duration of immunity to SARS-CoV-2. Even in the event of apparent elimination, SARS-CoV-2 surveillance should be maintained since a resurgence in contagion could be possible as late as 2024.


title: Guidance on the use of respiratory and facial protection equipment

text: Summary Infectious micro-organisms may be transmitted by a variety of routes, and some may be spread by more than one route. Respiratory and facial protection is required for those organisms that are usually transmitted via the droplet/airborne route, or when airborne particles have been artificially created, such as during ‘aerosol-generating procedures’. A range of personal protective equipment that provides different degrees of facial and respiratory protection is available. It is apparent from the recent experiences with severe acute respiratory syndrome and pandemic (H1N1) 2009 influenza that healthcare workers may have difficulty in choosing the correct type of facial and respiratory protection in any given clinical situation. To address this issue, the Scientific Development Committee of the Healthcare Infection Society established a short-life working group to develop guidance. The guidance is based upon a review of the literature, which is published separately, and expert consensus.


Personal View: Low-dose Lung Radiotherapy for COVID-19 Pneumonia – The Atypical Science and the Unknown Collateral Consequence


title: Global Research on Artemisinin and its Derivatives: Perspectives from Patents

text: BACKGROUND: The isolation of artemisinin in 1971 heralded the beginning of a new era in antimalarial drug therapy, and artemisinin-based combination therapies are currently the mainstay of malaria treatment worldwide. Artemisinin-related studies have been extensively and intensively executed in the last few decades. However, although many purely technological reviews have been completed in this field, studies on artemisinin from the perspective of patents are still very limited. In terms of the importance of patents for academic research and commercial development, this study aims to reveal the overall patent landscape of artemisinin in the temporal, spatial, and technological dimensions. This work may provide a useful reference for relevant decision-making by researchers, investors, and policymakers. METHODS: All available patent data relevant to artemisinin derivatives and artemisinin-based drug combinations developed for use in various therapeutic areas were collected from the Derwent Innovation database. Descriptive statistics and citation analyses were used to analyze the patent landscape. RESULTS: A total of 4594 patent documents and 1450 simple patent families from 1986 to 2019 were analyzed. A comprehensive patent landscape of artemisinin is presented from the aspects of time trends, filing countries, patent ownership, co-patents, technological categories, therapeutic areas, and citation networks and pathways. CONCLUSIONS: China and the United States are mainly responsible for the dramatic increase of artemisinin patents over the last three decades. From the point of view of patents, notable technological issues on artemisinin are chemical and biological synthesis, novel combinations, new formulations and administration routes, drug repositioning, and minimizing the resistance. Furthermore, a critical challenge lies in how to stimulate the industry to develop artemisinin-related drugs by government regulation and public-private partnership.


An overview of human parainfluenza virus 1-4 infections in northeastern Slovenia based on molecular detection


title: Disruptive Modifications to Cardiac Critical Care Delivery During the Covid-19 Pandemic: An International Perspective

text: Abstract The COVID-19 pandemic has presented a major unanticipated stress on our workforce, organizational structure, systems of care, and critical resource supply. In order to ensure provider safety, maximize efficiency, and optimize patient outcomes, health systems need to be agile. Critical care cardiologists may be uniquely positioned to treat the numerous respiratory and cardiovascular complications of the SARS-CoV-2 virus and support clinicians without critical care training who may be suddenly asked to care for critically ill patients. This manuscript draws upon the experiences of colleagues from heavily impacted regions of the United States and Europe as well as lessons learned from military mass casualty medicine. We offer pragmatic suggestions on how to implement scalable models for critical care delivery, cultivate educational tools for team training, and embrace technologies such as telemedicine to enable effective collaboration despite social distancing imperatives.


title: Mobilising the primary care UDCs during the COVID-19 pandemic

text: When the Chief Dental Officer for England announced that Urgent Dental Centres (UDCs) were to open during the COVID-19 pandemic, there were numerous hurdles that needed to be overcome prior to opening One of the biggest challenges, in addition to securing a supply of appropriate personal protective equipment (PPE), was the provision of training and testing of respiratory protective equipment (RPE) and the appropriate use of PPE in order to ensure that the dental workforce is safe to deliver face to face patient care


title: Évaluation par RT-PCR du portage nasopharyngé du SARS-Cov-2 chez les personnels de santé symptomatiques suspects de COVID-19 dans un CHU de la banlieue parisienne

text: INTRODUCTION: A consultation dedicated to symptomatic health professionals was opened at the beginning of the COVID-19 epidemic in order to meet the specific needs of this population. The objective of this work was to estimate the frequency of SARS-Cov-2 nasopharyngeal carriage in symptomatic healthcare workers suspected of having COVID-19 and to determine the factors associated with this carriage. METHODS: Of the 522 consultants, 308 worked in the Hospital and 214 outside. They had mild forms of COVID-19 and non-specific clinical signs with the exception of agueusia/anosmia, which was significantly more common in those with positive RT-PCR. The rate of RT-PCR positivity was 38% overall, without significant difference according to profession. It was higher among external consultants (47% versus 31%). In the hospital, this rate was significantly lower for symptomatic staff in the care sectors, compared to staff in the technical platforms and laboratories (24%, versus 45%, p = 0.006 and 54%, respectively, p < 0.001), but did not differ between staff in COVID units and other care sectors (30% versus 28%). Among the external consultants, the positivity rates of nursing home and private practices staff (53% and 55% respectively) were more than double that of acute care hospital staff (24%, p < 0.001). CONCLUSIONS: These data confirm the strong impact of COVID-19 on health professionals. The higher positivity rates among symptomatic professionals working outside the hospital compared to those working in hospital may be explained in part by a shortage of protective equipment and by difficulties in accessing virological diagnosis, which were greater outside the hospital when the epidemic began.


title: Effect of the COVID-19 Epidemic on Physical Activity in Community-Dwelling Older Adults in Japan: A Cross-Sectional Online Survey

text: OBJECTIVES: The objective of this study was to investigate changes in physical activity (PA) between January (before the COVID-19 epidemic) and April (during the COVID-19 epidemic) 2020 in community-dwelling older adults in Japan. DESIGN: Cross-sectional online survey. SETTING AND SUBJECTS: From April 23 to 27, 2020, an online survey was completed by 1,600 community-dwelling older adults in Japan. METHODS: We assessed the frailty status using the Kihon checklist, and other demographics and asked questions regarding PA at two time points: January and April 2020. We defined the total PA time (minutes) per week based on activity frequency and time. RESULTS: The study participants’ mean age, proportion of women, and prevalence of frailty were 74.0±5.6 years, 50% (n=800), and 24.3% (n=388), respectively. We found a significant decrease in total PA time in April 2020 (median [interquartile range (IQR)], 180 [0 to 420]) when compared to January 2020 (median [IQR], 245 [90 to 480]) (P<0.001). We also performed a subgroup analysis according to the frailty category; total PA time significantly decreased in April 2020 when compared to January 2020 for all frailty categories (P<0.001). CONCLUSION: In conclusion, due to the COVID-19 epidemic, the total PA time in April 2020 significantly decreased compared to that in January 2020 in older adults. This finding may lead to a higher incidence of disability in the near future in older people.


title: Risiken und Chancen von Immuntherapien in Zeiten der Coronavirus-2019-Pandemie

text: Immunotherapies form the essential basis of treatment for neuroinflammatory disease. However, in times of the coronavirus 2019 (COVID-19) pandemic, the question is increasingly arising in clinical routine as to whether immunotherapy should be initiated, intensified, paused, or even discontinued in neurological patients due to the risk of infection. Uncertainty is caused primarily due to the fact that a number of national and international scientific medical societies have published differing recommendations in this regard. This article provides an overview of the mechanisms of action of immunotherapies and the resulting risks of infection with COVID-19. Potential opportunities and beneficial effects of individual substrates in the acute treatment of COVID-19 are discussed.


title: Resumption of Respiratory Outpatient Services in the COVID-19 era: experience from Southern Italy

text: COVID-19 pandemic turned the entire health-care system organization upside-down, suspending elective activities and outpatient services. In Italy, we are entering a second phase of the pandemic and several strategies has been developed to “re-open” the country, some businesses, and also health-care outpatient activities. This manuscript describes the experience of a Southern Italy Respiratory Unit for safely resuming outpatient respiratory services and preventing COVID-19 transmission.


title: Code-based Syndromic Surveillance for Influenzalike Illness by International Classification of Diseases, Ninth Revision

text: With the spread of avian influenza, use of automated data streams to rapidly detect and track human influenza cases has increased. We performed correlation analyses to determine whether International Classification of Diseases, Ninth Revision (ICD-9), groupings used to detect influenzalike illness (ILI) within an automated syndromic system correlate with respiratory virus laboratory test results in the same population (r = 0.71 or 0.86, depending on group). We used temporal and signal-to-noise analysis to identify 2 subsets of ICD-9 codes that most accurately represent ILI trends, compared nationwide sentinel ILI surveillance data from the Centers for Disease Control and Prevention with the automated data (r = 0.97), and found the most sensitive set of ICD-9 codes for respiratory illness surveillance. Our results demonstrate a method for selecting the best group of ICD-9 codes to assist system developers and health officials who are interpreting similar data for daily public health activities.


title: Show me a man or a woman alone and I'll show you a saint: Changes in the frequency of criminal incidents during the COVID-19 pandemic

text: OBJECTIVES: To investigate the effect of the COVID-19 pandemic on the frequency of various crime types (property, violent, and mischief) in Vancouver, Canada. METHODS: Crime data representing residential burglary, commercial burglary, theft of vehicle, theft from vehicle, theft, violence, and mischief are analysed at the city level using interrupted time series techniques. RESULTS: While COVID-19 has not had an impact on all crime types, statistically significant change has been identified in a number of cases. Depending on the crime type, the magnitude and direction of the change in frequency varies. It is argued that (mandated) social restrictions, shifted activity patterns and opportunity structures which are responsible for these findings. CONCLUSIONS: We find support for changes in the frequency of particular crime types during the COVID-19 pandemic. This is important for criminal justice and social service practitioners when operating within an extraordinary event.


title: Early indication for a reduced burden of radiologically confirmed pneumonia in children following the introduction of routine vaccination against Haemophilus influenzae type b in Nha Trang, Vietnam

text: Abstract Introduction Despite the global success of Hib vaccination in reducing disease and mortality, uncertainty about the disease burden and the potential impact of Hib vaccination in Southeast Asia has delayed the introduction of vaccination in some countries in the region. Hib vaccination was introduced throughout Vietnam in July 2010 without catch-up. In an observational, population based surveillance study we estimated the impact of routine Hib vaccination on all cause radiologically confirmed childhood pneumonia in Nha Trang, Vietnam. Materials and methods In 2007 active hospital based surveillance was established in Khanh Hoa General Hospital, the only hospital in Nha Trang, Khanh Hoa province. Nasopharyngeal samples and chest radiographs are taken routinely from all children diagnosed with acute respiratory illness on admission. For admissions between 02/2007 and 03/2012 chest radiographs were interpreted for the presence of WHO primary endpoint pneumonia and nasopharyngeal swabs were analysed by PCR for the presence of Influenza A or B, RSV and rhinovirus. We employed Poisson regression to estimate the impact of Hib vaccination on radiologically confirmed pneumonia (RCP) while statistically accounting for potential differences in viral circulation in the post vaccination era which could have biased the estimate. Results Of 3151 cases admitted during the study period, 166 had RCP and major viruses were detected in 1601. The adjusted annual incidence of RCP in children younger than 5 years declined by 39% (12–58%) after introduction of Hib vaccination. This decline was most pronounced in children less than 2 years old, adjusted IRR: 0.52 (0.33–0.81), and no significant impact was observed in the 2–4 years old who were not eligible for vaccination, adjusted IRR: 0.96 (0.52–1.72). Discussion We present early evidence that the burden of Hib associated RCP in Nha Trang before vaccination was substantial and that shortly after introduction to the routine childhood immunisation scheme vaccination has substantially reduced that burden.


Minor aphthae associated with SARS‐CoV‐2 infection


title: Mortality and survival of COVID-19

text: This study aims to identify the risk factors associated with mortality and survival of COVID-19 cases in a state of the Brazilian Northeast. It is a historical cohort with a secondary database of 2070 people that presented flu-like symptoms, sought health assistance in the state and tested positive to COVID-19 until 14 April 2020, only moderate and severe cases were hospitalised. The main outcome was death as a binary variable (yes/no). It also investigated the main factors related to mortality and survival of the disease. Time since the beginning of symptoms until death/end of the survey (14 April 2020) was the time variable of this study. Mortality was analysed by robust Poisson regression, and survival by Kaplan–Meier and Cox regression. From the 2070 people that tested positive to COVID-19, 131 (6.3%) died and 1939 (93.7%) survived, the overall survival probability was 87.7% from the 24th day of infection. Mortality was enhanced by the variables: elderly (HR 3.6; 95% CI 2.3–5.8; P < 0.001), neurological diseases (HR 3.9; 95% CI 1.9–7.8; P < 0.001), pneumopathies (HR 2.6; 95% CI 1.4–4.7; P < 0.001) and cardiovascular diseases (HR 8.9; 95% CI 5.4–14.5; P < 0.001). In conclusion, mortality by COVID-19 in Ceará is similar to countries with a large number of cases of the disease, although deaths occur later. Elderly people and comorbidities presented a greater risk of death.


title: Antiviral Agents

text: Antiviral agents are drugs approved by the Food and Drug Administration (FDA) for the treatment or control of viral infections. Available antiviral agents mainly target stages in the viral life cycle. The target stages in the viral life cycle are; viral attachment to host cell, uncoating, synthesis of viral mRNA, translation of mRNA, replication of viral RNA and DNA, maturation of new viral proteins, budding, release of newly synthesized virus, and free virus in body fluids. At least half of available antiviral agents are for the treatment of human immunodeficiency virus (HIV) infections. The others are used mainly for the management of herpesviruses, hepatitis B virus (HBV), hepatitis C virus (HCV), and respiratory viruses. Antiviral agents can be used for prophylaxis, suppression, preemptive therapy, or treatment of overt disease. Two important factors that can limit the utility of antiviral drugs are toxicity and the development of resistance to the antiviral agent by the virus. In addition, host phenotypic behaviors toward antiviral drugs because of either genomic or epigenetic factors could limit the efficacy of an antiviral agent in an individual. This article summarizes the most relevant pharmacologic and clinical properties of current antiviral agents, and targets for novel antiviral agents.


The role of lung ultrasound in the assessment of novel coronavirus pneumonia


Anticipating and curtailing the Cardiometabolic toxicity of social isolation and emotional stress in the time of COVID-19


title: COVID-19, Medicine, and Sports

text: Abstract The COVID-19 outbreak has brought our lives to a sudden and complete lockdown. While the numbers of confirmed cases and deaths continue to rise, people around the world are taking brave actions to mitigate transmission and save lives. The role sports play in this pandemic is unprecedented, fascinating, and reveals the immense impact sports has on every aspect of our lives. We must all do our part to keep each other safe until this outbreak subsides and sports and humanity are back to being greater than ever.


title: Anticancer compound ABT-263 accelerates apoptosis in virus-infected cells and imbalances cytokine production and lowers survival rates of infected mice

text: ABT-263 and its structural analogues ABT-199 and ABT-737 inhibit B-cell lymphoma 2 (Bcl-2), BCL2L1 long isoform (Bcl-xL) and BCL2L2 (Bcl-w) proteins and promote cancer cell death. Here, we show that at non-cytotoxic concentrations, these small molecules accelerate the deaths of non-cancerous cells infected with influenza A virus (IAV) or other viruses. In particular, we demonstrate that ABT-263 altered Bcl-xL interactions with Bcl-2 antagonist of cell death (Bad), Bcl-2-associated X protein (Bax), uveal autoantigen with coiled-coil domains and ankyrin repeats protein (UACA). ABT-263 thereby activated the caspase-9-mediated mitochondria-initiated apoptosis pathway, which, together with the IAV-initiated caspase-8-mediated apoptosis pathway, triggered the deaths of IAV-infected cells. Our results also indicate that Bcl-xL, Bcl-2 and Bcl-w interact with pattern recognition receptors (PRRs) that sense virus constituents to regulate cellular apoptosis. Importantly, premature killing of IAV-infected cells by ABT-263 attenuated the production of key pro-inflammatory and antiviral cytokines. The imbalance in cytokine production was also observed in ABT-263-treated IAV-infected mice, which resulted in an inability of the immune system to clear the virus and eventually lowered the survival rates of infected animals. Thus, the results suggest that the chemical inhibition of Bcl-xL, Bcl-2 and Bcl-w could potentially be hazardous for cancer patients with viral infections.


title: Liver Transplantation in the Time of COVID19: Barriers and Ethical considerations for Management and Next Steps

text: The recent outbreak of the novel virus Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) which causes COVID19 disease has spread globally affecting millions of people. This pandemic has taxed our healthcare system and disrupted normal operations, even of lifesaving procedures like liver transplants. During these unprecedented times providers and patients are imperiled and resources for diagnosis and care may be limited. Continuing to perform resource intense advanced procedures is challenging, as is caring for patients with end‐stage liver disease or patients with urgent needs for liver tumor control. Liver transplantation in particular requires critical resources like blood products and critical care beds, which are fairly limited in the COVID19 pandemic. The potential of COVID19 infections in post‐transplant patients on immunosuppression and staff contacts further adds to the complexity. Therefore, transplant programs must re‐evaluate the ethicality, feasibility, and safety of performing liver transplants during this pandemic. Herein, we discuss the clinical and ethical challenges posed by performing liver transplants and offer guidance for managing patients with end‐stage liver disease during the COVID19 pandemic.


title: Spray dried plasma as an alternative to antibiotics in piglet feeds, mode of action and biosafety

text: The use of growth promoting and therapeutic antibiotics in piglet feed has been a concerning subject over the last few decades because of the risk of generating antimicrobial resistance that could be transferred to humans. As a result, many products have been proposed as potential alternatives to the use of antibiotics, and among these, spray dried plasma is considered one of the most promising. However, there have been concerns about its biosafety, particularly during periods of emergence or re-emergence of swine diseases in different regions of the world, such as the recent porcine epidemic diarrhea virus outbreak in North America. The objectives of this paper are to review recent publications about the use of spray dried plasma as an alternative to antibiotics in weaned pig diets, the possible mechanisms of action of spray dried plasma, and the existing evidence related to the biosafety of spray dried animal plasma. Particular attention is given to studies in which spray dried plasma has been directly compared to antibiotics or other alternative antimicrobial products. Several studies on the possible modes of action for spray dried plasma, such as preservation of gut barrier function or modulation of the immune response, are also reviewed. Finally, the paper focuses on the review of the existing studies on the risks of disease transmission with the use of spray dried plasma from porcine origin. Overall, spray dried plasma is a promising alternative to in-feed antimicrobials for piglets, particularly during the early stages of the post-weaning phase. Additionally, there is enough evidence to support that commercial spray dried porcine plasma is a safe product for pigs.


Leading with Empathy: Supporting Faculty through COVID‐19 and Beyond


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title: What comes after the ICU?

text: Some people with covid-19 need ventilation. Those who survive this will need a lot of physical and mental rehabilitation, finds Clare Wilson


title: Clinical Rounds

text: This section offers medicine-related news briefs as of July 1, 2020 A study found that warmer temperatures and ultraviolet (UV) light are not found to reduce the transmission of coronavirus disease-2019 (COVID-19) The JDRF/Beyond Type 1 Alliance collected best practices recommended by 50 global organizations for people with diabetes who contract COVID-19 The U S Food and Drug Administration (FDA) has banned the use of electrical stimulus devices(ESDs) for managing self-injurious behaviors


title: Novel hantavirus identified in black-bearded tomb bats, China

text: Abstract Hantaviruses cause life-threatening diseases in human worldwide. Rodents, insectivores and bats are known hantaviral reservoirs, but lack of complete genomic sequences of bat-borne hantaviruses impedes phylogenetic and evolutionary comparison with those of rodents and insectivores. Here, a novel bat-borne hantavirus, Laibin virus (LBV), has been identified in a black-bearded tomb bat in China. The complete genomic sequence shows that LBV is only distantly related to all previously known bat-borne hantaviruses.


COVID-19 pneumonia versus EVALI, distinguishing the overlapping CT features in the COVID-19 era


title: Electronic Health Record Documentation of Psychiatric Assessments in Massachusetts Emergency Department and Outpatient Settings During the Coronavirus Disease 2019 (COVID-19) Pandemic

text: This cohort study investigates the documentation of psychiatric symptoms in narrative clinical notes as coronavirus disease 2019 (COVID-19) prevalence increased in eastern Massachusetts.


title: Extensive homeostatic T cell phenotypic variation within the Collaborative Cross

text: The Collaborative Cross (CC) is a panel of reproducible recombinant inbred mouse strains with high levels of standing genetic variation, thereby affording unprecedented opportunity to perform experiments in a small animal model containing controlled genetic diversity while allowing for genetic replicates. Here, we advance the utility of this unique mouse resource for immunology research, as it allows for both examination and genetic dissection of mechanisms behind adaptive immune states in mice with distinct and defined genetic makeups. This approach is founded on quantitative trait locus mapping: identifying genetically variant genome regions associated with phenotypic variance in traits-of-interest. Furthermore, the CC can be utilized for mouse model development; distinct strains have unique immunophenotypes and immune properties, making them suitable for research on particular diseases and infections. Here, we describe variation in cellular immune phenotypes across F1 crosses of CC strains, and reveal quantitative trait loci responsible for several immune phenotypes.


title: Facing SARS-CoV-2 outbreak in immunotherapy era

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread represents a sanitary emergency all over the world. Viral biology is only partially known with some aspects in common with other CoV and the damage observed in most severe cases is due to intense inflammation. Immunotherapy restores immunological activity against cancer cells and it has become a standard treatment for several cancers. We carried out an examination of available data concerning with the effects exerted by both SARS-CoV-2 and the most widespread immunotherapy treatments on the immune system in order to hypothesize mechanisms underlying potential and mutual interaction. We provided an analysis of laboratory, clinical and therapeutic data related with severe acute respiratory syndrome coronavirus. We finally focused on implications of immunotherapy treatments in clinical practice.


title: Predicted protein interactions of IFITMs may shed light on mechanisms of Zika virus-induced microcephaly and host invasion

text: After the first reported case of Zika virus (ZIKV) in Brazil, in 2015, a significant increase in the reported cases of microcephaly was observed. Microcephaly is a neurological condition in which the infant’s head is significantly smaller with complications in brain development. Recently, two small membrane-associated interferon-inducible transmembrane proteins (IFITM1 and IFITM3) have been shown to repress members of the flaviviridae family which includes ZIKV. However, the exact mechanisms leading to the inhibition of the virus are yet unknown. Here, we assembled an interactome of IFITM1 and IFITM3 with known protein-protein interactions (PPIs) collected from publicly available databases and novel PPIs predicted using the High-confidence Protein-Protein Interaction Prediction (HiPPIP) model. We analyzed the functional and pathway associations of the interacting proteins, and found that there are several immunity pathways (toll-like receptor signaling, cd28 signaling in T-helper cells, crosstalk between dendritic cells and natural killer cells), neuronal pathways (axonal guidance signaling, neural tube closure and actin cytoskeleton signaling) and developmental pathways (neural tube closure, embryonic skeletal system development) that are associated with these interactors. Our novel PPIs associate cilia dysfunction in ependymal cells to microcephaly, and may also shed light on potential targets of ZIKV for host invasion by immunosuppression and cytoskeletal rearrangements. These results could help direct future research in elucidating the mechanisms underlying host defense to ZIKV and other flaviviruses.


title: The SARS-CoV-2 crisis - a crisis of reductionism?

text: Abstract Reductionism is ubiquitous in Medicine. In this paper, I argue that the current SARS-CoV-2 crisis is also a crisis of reductionism, with a narrow view on a virus without consideration of interdependencies between virology, epidemiology, immunity, economics and a diversity of other scientific disciplines. For optimal management of this crisis, systems thinking and transdisciplinary science would be much more appropriate. Some examples to underline my argument are provided.


title: Fosfomycin suppresses RS-virus-induced Streptococcus pneumoniae and Haemophilus influenzae adhesion to respiratory epithelial cells via the platelet-activating factor receptor

text: Human respiratory syncytial virus (RSV) sometimes causes acute and severe lower respiratory tract illness in infants and young children. The platelet-activating factor (PAF) receptor, which is a receptor for Streptococcus pneumoniae and Haemophilus influenzae, is upregulated by RSV infection in the pulmonary epithelial cell line A549. Fosfomycin, an antimicrobial agent, significantly suppressed PAF receptor induction by RSV infection at the mRNA and cell surface expression levels. Fosfomycin also suppressed RSV-induced adhesion of fluorescence-labeled S. pneumoniae and H. influenzae cells, as determined by flow cytometry and fluorescence microscopy. The RSV-induced bacterial adhesion was suggested to be host-PAF-receptor and bacterial-phosphocholine mediated. Fosfomycin, which has been shown to exhibit antimicrobial and immunomodulatory activities, was found here to suppress adhesion by disease-causing bacteria. Thus, fosfomycin might prevent secondary bacterial infection during RSV infection.


Progress and Concept for COVID‐19 Vaccine Development


title: Complete Heart Block, Severe Ventricular Dysfunction and Myocardial Inflammation in a Child with COVID-19 Infection

text: Abstract A young child presented with severe ventricular dysfunction and troponin leak in the setting of Coronavirus-19 disease (COVID-19). He developed intermittent, self-resolving, and hemodynamically insignificant episodes of complete heart block (CHB), which were diagnosed on telemetry and managed conservatively. This report is the first description of COVID-19 induced transient CHB in a child.


title: The effects of renin-angiotensin system inhibitors (RASI) in Corona Virus Disease (COVID-19) with Hypertension: A retrospective, single-center trial

text: Abstract Introduction and objective: A recent outbreak of Coronavirus disease 2019 (COVID-19) occurs in the worldwide. Angiotensin-converting enzyme 2 (ACE2) can mediate coronavirus entry into host cells. Therefore, renin-angiotensin system inhibitors (RASI) were suspected of contributing to the increase of coronavirus infection. We aimed to analyze the effects of RASI in COVID-19 patients with Hypertension. Patients and method: In this retrospective, single-center study, 27 COVID-19 patients with hypertension, who were admitted to the Shanghai Public Health Clinical Center from January 25, 2020 to January 31, 2020, were analyzed for clinical features, laboratory parameters, medications and the length of stay. All the patients were given antiviral and antihypertension treatment, of which 14 patients were treated with RASI and 13 patients without RASI. Results: Comparing the two groups, we did not found statistically significant differences in clinical symptoms and laboratory tests. Furthermore, cough was not aggravated. Conclusions: Through the analysis of this small sample, RASI could be deemed safe and effective to control high blood pressure of COVID-19 patients. Further analysis with a larger sampling size is required to explore the underlying mechanisms.


title: Tissue compartmentalization of T cell responses during early life

text: The immune system in early life is tasked with transitioning from a relatively protected environment to one in which it encounters a wide variety of innocuous antigens and dangerous pathogens. The immaturity of the developing immune system, and particularly the distinct functionality of T lymphocytes in early life, has been implicated in increased susceptibility to infection. Previous work has demonstrated that immune responses in early life are skewed toward limited inflammation and atopy; however, there is mounting evidence that such responses are context- and tissue-dependent. The regulation, differentiation, and maintenance of infant T cell responses, particularly as it relates to tissue compartmentalization, remains poorly understood. How the tissue environment impacts early-life immune responses and whether the development of localized protective immune memory cell subsets are established is an emerging area of research. As infectious diseases affecting the respiratory and digestive tracts are a leading cause of morbidity and mortality worldwide in infants and young children, a deeper understanding of site-specific immunity is essential to addressing these challenges. Here, we review the current paradigms of T cell responses during infancy as they relate to tissue localization and discuss implications for the development of vaccines and therapeutics.


title: COVID-19: Abnormal liver function tests

text: BACKGROUND & AIMS: Recent data on the coronavirus disease 2019 (COVID-19) outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has begun to shine light on the impact of the disease on the liver. But no studies to date have systematically described liver test abnormalities in patients with COVID-19. We evaluated the clinical characteristics of COVID-19 in patients with abnormal liver test results. METHODS: Clinical records and laboratory results were obtained from 417 patients with laboratory-confirmed COVID-19 who were admitted to the only referral hospital in Shenzhen, China from January 11 to February 21, 2020 and followed up to March 7, 2020. Information on clinical features of patients with abnormal liver tests were collected for analysis. RESULTS: Of 417 patients with COVID-19, 318 (76.3%) had abnormal liver test results and 90 (21.5%) had liver injury during hospitalization. The presence of abnormal liver tests became more pronounced during hospitalization within 2 weeks, with 49 (23.4%), 31 (14.8%), 24 (11.5%) and 51 (24.4%) patients having alanine aminotransferase, aspartate aminotransferase, total bilirubin and gamma-glutamyl transferase levels elevated to more than 3× the upper limit of normal, respectively. Patients with abnormal liver tests of hepatocellular type or mixed type at admission had higher odds of progressing to severe disease (odds ratios [ORs] 2.73; 95% CI 1.19–6.3, and 4.44, 95% CI 1.93–10.23, respectively). The use of lopinavir/ritonavir was also found to lead to increased odds of liver injury (OR from 4.44 to 5.03, both p <0.01). CONCLUSION: Patients with abnormal liver tests were at higher risk of progressing to severe disease. The detrimental effects on liver injury mainly related to certain medications used during hospitalization, which should be monitored and evaluated frequently. LAY SUMMARY: Data on liver tests in patients with COVID-19 are scarce. We observed a high prevalence of liver test abnormalities and liver injury in 417 patients with COVID-19 admitted to our referral center, and the prevalence increased substantially during hospitalization. The presence of abnormal liver tests and liver injury were associated with the progression to severe pneumonia. The detrimental effects on liver injury were related to certain medications used during hospitalization, which warrants frequent monitoring and evaluation for these patients.


title: The Unexpected Risks of COVID-19 on Asthma Control in Children

text: Abstract Much is being learned about clinical outcomes for adult COVID-19 patients with underlying chronic conditions, however, there is less coverage on how the COVID-19 pandemic impacts the management of chronic medical conditions in children and youth, such as asthma. Asthma is a common chronic medical condition in children that is uniquely susceptible to changes brought upon by COVID-19. Sudden dramatic changes in the environment, medical practice, and medication use have altered the asthma management landscape with potential impacts on asthma outcomes. In this paper, we review how changes in transportation and travel patterns, school attendance, physical activity, and time spent indoors, along with changes in healthcare delivery since the start of the pandemic all play a contributing role in asthma control in children. We review potentially important influences of asthma control in children during the COVID-19 pandemic worthy of further study.


title: Development, Implementation, and Process Evaluation of a Regional Palliative Care Quality Improvement Project

text: Abstract The delivery of optimal palliative care requires an integrated and coordinated approach of many health care providers across the continuum of care. In response to identified gaps in the region, the Palliative Care Integration Project (PCIP) was developed to improve continuity and decrease variability of care to palliative patients with cancer. The infrastructure for the project included multi-institutional and multisectoral representation on the Steering Committee and on the Development, Implementation and Evaluation Working Groups. After review of the literature, five Collaborative Care Plans and Symptom Management Guidelines were developed and integrated with validated assessment tools (Edmonton Symptom Assessment System and Palliative Performance Scale). These project resources were implemented in the community, the palliative care unit, and the cancer center. Surveys were completed by frontline health professionals (defined as health professionals providing direct care), and two independent focus groups were conducted to capture information regarding: 1) the development of the project and 2) the processes of implementation and usefulness of the different components of the project. Over 90 individuals from more than 30 organizations were involved in the development, implementation, and evaluation of the PCIP. Approximately 600 regulated health professionals and allied health professionals who provided direct care, and over 200 family physicians and medical residents, received education/training on the use of the PCIP resources. Despite unanticipated challenges, frontline health professionals reported that the PCIP added value to their practice, particularly in the community sector. The PCIP showed that a network in which each organization had ownership and where no organization lost its autonomy, was an effective way to improve integration and coordination of care delivery.


title: Immune response of AA broilers to IBV H120 vaccine and sodium new houttuyfonate

text: Abstract In this report, 120 healthy one-day-old AA broilers were divided into six groups. Groups 1–4 received 100, 200, 400 and 800mg/L of sodium new houttuyfonate (SNH) with IB vaccine H120 respectively. Group 5 received PBS and H120 and group 6 IL-2 and H120. The chickens were inoculated at 7 and 14days of age. On 0, 7, 14, 21, 28 and 35 post first vaccination, the dynamic changes of peripheral lymphocyte proliferation, cytokine assays and serum antibody titers were assayed respectively by MTT method, ELISA and hemagglutination inhibition assay (HI). The results showed that sodium new houttuyfonate significantly raised IB antibody titer in the chickens and also markedly promoted lymphocyte proliferation. The serum levels of IFN-γ and IL-4 in groups 1–4 were higher than those in groups 5 and 6. Hence, the immunologic enhancement of SNH was slightly superior to that of IL-2 adjuvant. Following challenge with IBV, chickens inoculated with SNH showed fewer and less severe clinical signs, lower death rate and less kidney pathology, as compared to those of the control groups. It indicated that SNH could enhance immune responses and increase protection against virulent IBV challenge in chickens.


COVID-19 y shock cardiogénico: diferentes formas de presentación cardiovascular con alta mortalidad


title: What are the pros and cons of the use of host-targeted agents against hepatitis C?

text: Abstract Hepatitis C virus (HCV) therapy is living a revolution. Host-targeted agents (HTAs) block HCV production by interacting with host cell components. Because they target conserved host proteins, not variable viral proteins, HTAs have the potential for pangenotypic antiviral activity and a high barrier to resistance. Only two HTAs have reached clinical development, including specific inhibitors of cyclophilin A peptidyl-prolyl cis/trans isomerase activity and antagonists of microRNA-122. Cyclophilin inhibitors have proven to be relatively well tolerated and can be confidently used as backbones of all-oral, interferon-free regimens. In addition, HTAs such as cyclophilin inhibitors offer opportunities for “panviral” approaches when they target mechanisms common to viruses of the same or different families. This article forms part of a symposium in Antiviral Research on “Hepatitis C: next steps toward global eradication.”


Prise en charge adaptée au COVID-19


title: Treatment Approach to Coronavirus Disease (COVID-19) Seen Early After Open Heart Surgery. Case Report

text: SARS-CoV-2 was reported for the first time in China on December 31, 2019, as the cause of some pneumonia cases characterized by fever, cough, dyspnea, myalgia, and fatigue. Here, we present our approach to a 54-year-old male patient who had coronary artery bypass (CABG) surgery diagnosed as high probability coronavirus disease 2019 (COVID-19) in early postoperative period.


title: Advancing Planetary Health in Australia: focus on emerging infections and antimicrobial resistance

text: With rising population numbers, anthropogenic changes to our environment and unprecedented global connectivity, the World Economic Forum ranks the spread of infectious diseases second only to water crises in terms of potential global impact. Addressing the diverse challenges to human health and well-being in the 21st century requires an overarching focus on ‘Planetary Health’, with input from all sectors of government, non-governmental organisations, academic institutions and industry. To clarify and advance the Planetary Health agenda within Australia, specifically in relation to emerging infectious diseases (EID) and antimicrobial resistance (AMR), national experts and key stakeholders were invited to a facilitated workshop. EID themes identified included animal reservoirs, targeted surveillance, mechanisms of emergence and the role of unrecognised human vectors (the ‘invisible man’) in the spread of infection. Themes related to AMR included antimicrobial use in production and companion animals, antimicrobial stewardship, novel treatment approaches and education of professionals, politicians and the general public. Effective infection control strategies are important in both EID and AMR. We provide an overview of key discussion points, as well as important barriers identified and solutions proposed.


CORONAVIRUS: Severe Blow to Growth


title: Antibodies derived from a toxoid MEFA (multiepitope fusion antigen) show neutralizing activities against heat-labile toxin (LT), heat-stable toxins (STa, STb), and Shiga toxin 2e (Stx2e) of porcine enterotoxigenic Escherichia coli (ETEC)

text: Abstract Enterotoxigenic Escherichia coli (ETEC) strains are the main cause of diarrhea in pigs. Pig diarrhea especially post-weaning diarrhea remains one of the most important swine diseases. ETEC bacterial fimbriae including K88, F18, 987P, K99 and F41 promote bacterial attachment to intestinal epithelial cells and facilitate ETEC colonization in pig small intestine. ETEC enterotoxins including heat-labile toxin (LT) and heat-stable toxins type Ia (porcine-type STa) and type II (STb) stimulate fluid hyper-secretion, leading to watery diarrhea. Blocking bacteria colonization and/or neutralizing enterotoxicity of ETEC toxins are considered effective prevention against ETEC diarrhea. In this study, we applied the MEFA (multiepitope fusion antigen) strategy to create toxoid MEFAs that carried antigenic elements of ETEC toxins, and examined for broad antitoxin immunogenicity in a murine model. By embedding STa toxoid STaP12F (NTFYCCELCCNFACAGCY), a STb epitope (KKDLCEHY), and an epitope of Stx2e A subunit (QSYVSSLN) into the A1 peptide of a monomeric LT toxoid (LTR192G), two toxoid MEFAs, ‘LTR192G-STb-Stx2e-STaP12F’ and ‘LTR192G-STb-Stx2e-3xSTaP12F’ which carried three copies of STaP12F, were constructed. Mice intraperitoneally immunized with each toxoid MEFA developed IgG antibodies to all four toxins. Induced antibodies showed in vitro neutralizing activities against LT, STa, STb and Stx2e toxins. Moreover, suckling piglets born by a gilt immunized with ‘LTR192G-STb-Stx2e-3xSTaP12F’ were protected when challenged with ETEC strains, whereas piglets born by a control gilt developed diarrhea. Results from this study showed that the toxoid MEFA induced broadly antitoxin antibodies, and suggested potential application of the toxoid MEFA for developing a broad-spectrum vaccine against ETEC diarrhea in pigs.


title: Genotypic and phenotypic characterization of the California 99 (Cal99) variant of infectious bronchitis virus

text: The California 99 (Cal99) variant of infectious bronchitis virus (IBV) was first recovered in 1999 from vaccinated broiler chicken flocks in Central California. The S1 hypervariable region of Cal99 genome was most closely related to Arkansas (Ark) serotype viruses. In this study, the complete genome of Cal99 was sequenced, and the structural protein genes were compared with those of commonly used IBV vaccines as well as those of isolates from naturally occurring outbreaks in different parts of the world, to elucidate potential sources of genetic material. Based on sequence comparison, the prototype Cal99 virus is similar to the apathogenic ArkDPI virus, except in the S1 gene and stretches of sequence in the S2 and M structural protein genes, which are more related to Connecticut (Conn) and Massachusetts (Mass) strain viruses, respectively. We speculate that these two fragments came from a Conn and a Mass virus, respectively, and were incorporated into a virus largely derived from ArkDPI. Since Ark, Conn and Mass strains have been simultaneously used as live vaccines in California, both point mutations and recombination among vaccine strains may have contributed to the emergence of the Cal99 variant virus. Analysis of the structural protein genes of six Cal99 isolates demonstrated that viruses of this serotype may differ substantially in the non-S1 structural genes. Finally, we performed a challenge study with Cal99 and demonstrated that the virus causes late-onset respiratory disease, with a severity comparable to that of the M41 IBV challenge strain.


title: Combating the Coronavirus Pandemic: Early Detection, Medical Treatment, and a Concerted Effort by the Global Community

text: The World Health Organization (WHO) has declared the outbreak of 2019 novel coronavirus, known as 2019-nCoV, a pandemic, as the coronavirus has now infected over 2.6 million people globally and caused more than 185,000 fatalities as of April 23, 2020. Coronavirus disease 2019 (COVID-19) causes a respiratory illness with symptoms such as dry cough, fever, sudden loss of smell, and, in more severe cases, difficulty breathing. To date, there is no specific vaccine or treatment proven effective against this viral disease. Early and accurate diagnosis of COVID-19 is thus critical to curbing its spread and improving health outcomes. Reverse transcription-polymerase chain reaction (RT-PCR) is commonly used to detect the presence of COVID-19. Other techniques, such as recombinase polymerase amplification (RPA), loop-mediated isothermal amplification (LAMP), clustered regularly interspaced short palindromic repeats (CRISPR), and microfluidics, have allowed better disease diagnosis. Here, as part of the effort to expand screening capacity, we review advances and challenges in the rapid detection of COVID-19 by targeting nucleic acids, antigens, or antibodies. We also summarize potential treatments and vaccines against COVID-19 and discuss ongoing clinical trials of interventions to reduce viral progression.


title: First evidence of the emergence of novel putative infectious bronchitis virus genotypes in Cuba

text: Abstract The emergence of new infectious bronchitis virus (IBV) genotypes or serotypes along with the poor cross-protection observed among IBV serotypes have complicated the avian infectious bronchitis (IB) control programs in different geographic regions. In Cuba, the lack of genetic information regarding IBV and the increasing epidemiological importance of this virus in Cuban chicken flocks demand further characterization of IBV isolates. In the present work, studies of genetic diversity and phylogenetic relationships among recent IBV isolates from Cuban chicken flocks showing respiratory disorders were performed. Two putative genotypes genetically different to the Massachusetts genotype H120 strain used in the Cuban vaccination program were found in the flocks assessed. In addition, a potential nephropathogenic IBV isolate was found by first time in Cuba.


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title: Rapid Deployment of a Statewide COVID‐19 ECHO Program for Frontline Clinicians: Early Results and Lessons Learned


title: Molecular epidemiology and evolution of avian infectious bronchitis virus in Spain over a fourteen-year period

text: Abstract An in-depth molecular study of infectious bronchitis viruses (IBV) with particular interest in evolutionary aspects of IBV in Spain was carried out in the present study based on the S1 gene molecular characterization of twenty-six Spanish strains isolated over a fourteen-year period. Four genotypes were identified based on S1 gene sequence analyses and phylogenetic studies. A drastic virus population shift was demonstrated along time and the novel Italy 02 serotype was shown to have displaced the previous predominant serotype 4/91 in the field. Detailed analyses of synonymous to non-synonymous ratio of the S1 gene sequences of this new serotype Italy 02 suggested positive selection pressures might have contributed to the successful establishment of Italy 02 serotype in our country. In addition, differences on the fitness abilities of new emergent genotypes were indicated. Furthermore, intergenic sequences (IGs)-like motifs within S1 gene sequences of IBV isolates were suggested to enhance the recombination abilities of certain serotypes.


title: UK newspapers' representations of the 2009–10 outbreak of swine flu: one health scare not over-hyped by the media?

text: BACKGROUND: A/H1N1, more commonly referred to as swine flu, emerged in Mexico in spring 2009. It rapidly spread across the world and was classed as a global pandemic on 11 June 2009. OBJECTIVE: To analyse UK newsprint coverage of the swine flu pandemic. METHODS: Content analysis of 2374 newsprint articles published in eight UK national newspapers between 1 March 2009 and 28 February 2010. RESULTS: Newsprint coverage of the swine flu epidemic was immense. The threat from swine flu was portrayed as greatest in the spring and summer of 2009 when scientific uncertainties about the impact on the UK and global population were at their height and when swine flu cases in the UK first peaked. Thereafter the number of news articles waned, failing to mirror the October peak in flu cases as the virus failed to be as virulent as first feared. Content analysis found little evidence of the media ‘over-hyping’ the swine flu pandemic. CONCLUSIONS: The news media's role as a disseminator of scientific information is particularly important in areas of risk perception. Despite a succession of health scares in recent years in which the media has been accused of exaggerating the risks and contributing to public misunderstandings of the issues, this analysis suggests that the UK newsprint reporting of swine flu in the 2009–10 outbreak was largely measured. The news media's role as disseminators of factual health information on swine flu is to be welcomed, particularly in relation to their handling and responsible reporting on scientific uncertainty.


title: Chapter 9 Gene Therapy for Respiratory Viral Infections

text: Abstract Pulmonary infections by viruses may result in serious diseases of public health importance. The problems of the infections are exacerbated by rapid transmission of the pathogenic agents, which occur through inhalation and direct contact with contaminated surfaces. Moreover, cross-species transmission resulting from changes to viral genetic makeup poses a risk for emergence of pathogens with new characteristics, which in some cases may be responsible for causing different diseases. With the advent of efficient sequencing and nucleic acid-based virus-disabling technologies, gene therapy is well placed to advance new treatments to counter respiratory infections. Most studies aimed at using nucleic acids to treat respiratory viral infections have used RNA interference (RNAi) to silence viral gene targets. A few studies have used silencing of host factors required by the viruses as a means of inhibiting viral replication and preventing emergence of escape mutants. By administering antivirals to the airways, studies performed in vivo have taken advantage of the anatomy of the respiratory system to deliver therapeutic nucleic acids. Reported data have shown proof of principle of efficacy of gene therapy in models of respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus, influenza virus A, and measles virus, among others. RNAi-based gene therapy has been advanced to clinical trial for treatment of RSV infection. Although the primary endpoint was not met in an intent-to-treat analysis, the investigation has provided useful information for the advancement of gene therapy for current and emergent respiratory infections.


title: World wide web resources on control of nosocomial infections

text: Nosocomial infections are a major worldwide cause of death and disability, infection control programs are effective in limiting these infections, especially those acquired in the intensive care unit. The development of the world wide web has provided health care professionals with immediate access to continuously updated information in the field of infection control. We sought to identify websites that contain information on nosocomial infection control by using popular internet search engines, such as Google, Yahoo and AltaVista, and by reviewing relevant publications identified in the PubMed and Current Contents databases. Only those sites that were English language, open access, and developed by a government, academic institution, or national or international scientific association were eligible for inclusion. From a vast number of internet sites initially identified, we selected 49 that provide information on infection control for inclusion in our list of practical and relevant internet resources. Several sites provide general information on infection control practices, whereas others focus on one or a few specific infection(s). We provide health care professionals with a timely and succinct list of open access internet resources that contain information regarding the prevention and control of nosocomial infections in order to help in the dissemination of relevant information and so contribute to the limitation of such hazards.


title: SARS Coronavirus Detection Methods

text: Using clinical samples from patients with severe acute respiratory syndrome, we showed that the sensitivities of a quantitative reverse transcription–polymerase chain reaction (80% for fecal samples and 25% for urine samples) were higher than those of the polyclonal (50% and 5%) and monoclonal (35% and 8%) antibody-based nucleocapsid antigen capture enzyme-linked immunosorbent assays.


title: Fighting against COVID-19: Innovative strategies for clinical pharmacists

text: Abstract Background Clinical pharmacists’ routine task is carrying out pharmaceutical care to ensure patients' safe and reasonable medication use. However, under public health emergencies, such as the outbreak of COVID-19, the work strategies of clinical pharmacists need to be modified according to the rapid spread of the disease, where information and resources are usually lack to guide them. Objective To retrieve and investigate the prevention and control measures of clinical pharmacists during the outbreak of novel coronavirus, summarize the roles and responsibilities of clinical pharmacists, and to propose innovative strategies for developing pharmacy services under the epidemic. Methods The Chinese and English databases, self-media network, website of professional society or medical institution, and clinical trial center platforms were searched, and clinical pharmacists involved in the work against COVID-19 were surveyed and interviewed. Investigate the challenges and needs of frontline medical staffs for treating patients, and formulate strategies based on the actual medical environment. Results Clinical pharmacists play a vital role in leading the industry to formulate work instructions, provide frontline medical staff with drug information, and develop innovative pharmacy services to promote the rational use of medicines with collaborative teamwork and close communication according to the epidemic situation of COVID-19. Anti-epidemic work indeed has driven the development of remote pharmacy services. Conclusion Facing public health emergencies, clinical pharmacists can give full play to their professional expertise, analyze the current situation rationally, formulate telehealth strategies swiftly, and work in a united and efficient manner to provide innovative pharmacy services to ensure medication safety and rational use of medicine.


title: A novel peptide with potent and broad-spectrum antiviral activities against multiple respiratory viruses

text: A safe, potent and broad-spectrum antiviral is urgently needed to combat emerging respiratory viruses. In light of the broad antiviral activity of β-defensins, we tested the antiviral activity of 11 peptides derived from mouse β-defensin-4 and found that a short peptide, P9, exhibited potent and broad-spectrum antiviral effects against multiple respiratory viruses in vitro and in vivo, including influenza A virus H1N1, H3N2, H5N1, H7N7, H7N9, SARS-CoV and MERS-CoV. The antiviral activity of P9 was attributed to its high-affinity binding to viral glycoproteins, as well as the abundance of basic amino acids in its composition. After binding viral particles through viral surface glycoproteins, P9 entered into cells together with the viruses via endocytosis and prevented endosomal acidification, which blocked membrane fusion and subsequent viral RNA release. This study has paved the avenue for developing new prophylactic and therapeutic agents with broad-spectrum antiviral activities.


title: Timing of antiviral treatment initiation is critical to reduce SARS-Cov-2 viral load

text: We modeled the viral dynamics of 13 untreated patients infected with SARS-CoV-2 to infer viral growth parameters and predict the effects of antiviral treatments. In order to reduce peak viral load by more than 2 logs, drug efficacy needs to be greater than 80% if treatment is administered after symptom onset; an efficacy of 50% could be sufficient if treatment is initiated before symptom onset. Given their pharmacokinetic/pharmacodynamic properties, current investigated drugs may be in a range of 20-70% efficacy. They may help control virus if administered very early, but may not have a major effect in severe patients.


title: Human Coronavirus EMC Is Not the Same as Severe Acute Respiratory Syndrome Coronavirus

text: A newly identified betacoronavirus, human coronavirus EMC (HCoV-EMC), has been isolated from several patients with respiratory and renal disease in the Middle East. While only a few infected patients have been identified, the mortality of the infection is greater than 50%. Like its better-known cousin severe acute respiratory syndrome coronavirus (SARS-CoV), HCoV-EMC appears to have originated from bats. In a recent article in mBio, Müller et al. described several important differences between the two viruses [M. A. Müller et al., mBio 3(6):e00515-12, 2012, doi:10.1128/mBio.00515-12]. Unlike SARS-CoV, HCoV-EMC can directly infect bat cells. As important, HCoV-EMC does not enter cells using the SARS-CoV receptor, human angiotensin-converting receptor-2 (hACE2). These results provide a strong incentive for identifying the host cell receptor used by HCoV-EMC. Identification of the receptor will provide insight into the pathogenesis of pulmonary and renal disease and may also suggest novel therapeutic interventions.


title: Epidemiological and clinical characteristics of three family clusters of COVID-19 transmitted by latent patients in China

text: From 21 January 2020 to 9 February 2020, three family clusters involving 31 patients with coronavirus disease 2019 were identified in Wenzhou, China. The epidemiological and clinical characteristics of the family cluster patients were analysed and compared with those of 43 contemporaneous sporadic cases. The three index cases transmitted the infection to 28 family members 2–10 days before illness onset. Overall, 28 of the 41 sporadic cases and three of 31 patients in the family clusters came back from Wuhan (65.12 vs. 9.68%, P< 0.001). In terms of epidemiological characters and clinical symptoms, no significant differences were observed between the family cluster and sporadic cases. However, the lymphocyte counts of sporadic cases were significantly lower than those of family cluster cases ((1.32 ± 0.55) × 10(9)/l vs. (1.63 ± 0.70) × 10(9)/l, P = 0.037), and the proportion of hypoalbuminaemia was higher in sporadic cases (18/43, 41.86%) than in the family clusters (6/31, 19.35%) (P < 0.05). Within the family cluster, the second- and third-generation cases had milder clinical manifestations, without severe conditions, compared with the index and first-generation cases, indicating that the virulence gradually decreased following passage through generations within the family clusters. Close surveillance, timely recognition and isolation of the suspected or latent patient is crucial in preventing family cluster infection.


title: Simian adenovirus vector production for early-phase clinical trials: A simple method applicable to multiple serotypes and using entirely disposable product-contact components

text: A variety of Good Manufacturing Practice (GMP) compliant processes have been reported for production of non-replicating adenovirus vectors, but important challenges remain. Most clinical development of adenovirus vectors now uses simian adenoviruses or rare human serotypes, whereas reported manufacturing processes mainly use serotypes such as AdHu5 which are of questionable relevance for clinical vaccine development. Many clinically relevant vaccine transgenes interfere with adenovirus replication, whereas most reported process development uses selected antigens or even model transgenes such as fluorescent proteins which cause little such interference. Processes are typically developed for a single adenovirus serotype – transgene combination, requiring extensive further optimization for each new vaccine. There is a need for rapid production platforms for small GMP batches of non-replicating adenovirus vectors for early-phase vaccine trials, particularly in preparation for response to emerging pathogen outbreaks. Such platforms must be robust to variation in the transgene, and ideally also capable of producing adenoviruses of more than one serotype. It is also highly desirable for such processes to be readily implemented in new facilities using commercially available single-use materials, avoiding the need for development of bespoke tools or cleaning validation, and for them to be readily scalable for later-stage studies. Here we report the development of such a process, using single-use stirred-tank bioreactors, a transgene-repressing HEK293 cell – promoter combination, and fully single-use filtration and ion exchange components. We demonstrate applicability of the process to candidate vaccines against rabies, malaria and Rift Valley fever, each based on a different adenovirus serotype. We compare performance of a range of commercially available ion exchange media, including what we believe to be the first published use of a novel media for adenovirus purification (NatriFlo® HD-Q, Merck). We demonstrate the need for minimal process individualization for each vaccine, and that the product fulfils regulatory quality expectations. Cell-specific yields are at the upper end of those previously reported in the literature, and volumetric yields are in the range 1 × 10(13) – 5 × 10(13) purified virus particles per litre of culture, such that a 2–4 L process is comfortably adequate to produce vaccine for early-phase trials. The process is readily transferable to any GMP facility with the capability for mammalian cell culture and aseptic filling of sterile products.


title: The early landscape of COVID‐19 vaccine development in the UK and rest of the world

text: Since the first WHO notification on 31st December 2019, COVID‐19, the respiratory disease caused by the coronavirus SARS‐CoV‐2, has been responsible for over 4 million confirmed infections, and almost 300,000 deaths worldwide. The pandemic has led to over half of the world's population living under lockdown conditions. To allow normal life to resume, public health interventions will be needed to prevent further waves of infections as lockdown measures are lifted. As one of the most effective countermeasures against infectious diseases, an efficacious vaccine is considered crucial to containing the COVID‐19 pandemic. Following the publication of the genome sequence of SARS‐CoV‐2, vaccine development has accelerated at an unprecedented pace across the world. Here we review the different platforms employed to develop vaccines, the standard timelines of development and how they can be condensed in a pandemic situation. We focus on vaccine development in the UK and vaccines which have entered clinical trials around the world.


title: Lyon-IARC Polyomavirus DNA in Feces of Diarrheic Cats

text: A viral metagenomic analysis of feces from an unexplained outbreak of feline diarrhea revealed the presence of Lyon-IARC polyomavirus (LIPyV) DNA. LIPyV, whose genome was originally sequenced from swabs of human skin, was fecally shed by three out of five diarrheic cats.


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title: The hookworm Ancylostoma ceylanicum intestinal transcriptome provides a platform for selecting drug and vaccine candidates

text: BACKGROUND: The intestine of hookworms contains enzymes and proteins involved in the blood-feeding process of the parasite and is therefore a promising source of possible vaccine antigens. One such antigen, the hemoglobin-digesting intestinal aspartic protease known as Na-APR-1 from the human hookworm Necator americanus, is currently a lead candidate antigen in clinical trials, as is Na-GST-1 a heme-detoxifying glutathione S-transferase. METHODS: In order to discover additional hookworm vaccine antigens, messenger RNA was obtained from the intestine of male hookworms, Ancylostoma ceylanicum, maintained in hamsters. RNA-seq was performed using Illumina high-throughput sequencing technology. The genes expressed in the hookworm intestine were compared with those expressed in the whole worm and those genes overexpressed in the parasite intestine transcriptome were further analyzed. RESULTS: Among the lead transcripts identified were genes encoding for proteolytic enzymes including an A. ceylanicum APR-1, but the most common proteases were cysteine-, serine-, and metallo-proteases. Also in abundance were specific transporters of key breakdown metabolites, including amino acids, glucose, lipids, ions and water; detoxifying and heme-binding glutathione S-transferases; a family of cysteine-rich/antigen 5/pathogenesis-related 1 proteins (CAP) previously found in high abundance in parasitic nematodes; C-type lectins; and heat shock proteins. These candidates will be ranked for downstream antigen target selection based on key criteria including abundance, uniqueness in the parasite versus the vertebrate host, as well as solubility and yield of expression. CONCLUSION: The intestinal transcriptome of A. ceylanicum provides useful information for the identification of proteins involved in the blood-feeding process, representing a first step towards a reverse vaccinology approach to a human hookworm vaccine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-016-1795-8) contains supplementary material, which is available to authorized users.


The Ethics of Scare: COVID-19 and the Philippines’ Fear Appeals


title: Survey: BH organizations closing programs, reducing staff amid pandemic

text: Behavioral health organizations have canceled, rescheduled and even turned away patients, according to results of a new survey on the economic impact of COVID‐19 — an impact felt even more among smaller organizations. The survey of 880 community behavioral health organizations (CBHOs) around the country served to clarify the impact of the virus on patients, employment safety and financial viability.


title: Complete genomic sequences, a key residue in the spike protein and deletions in non-structural protein 3b of US strains of the virulent and attenuated coronaviruses, transmissible gastroenteritis virus and porcine respiratory coronavirus

text: Transmissible gastroenteritis virus (TGEV) isolates that have been adapted to passage in cell culture maintain their infectivity in vitro but may lose their pathogenicity in vivo. To better understand the genomic mechanisms for viral attenuation, we sequenced the complete genomes of two virulent TGEV strains and their attenuated counterparts: virulent TGEV Miller M6 and attenuated TGEV Miller M60 and virulent TGEV Purdue and attenuated TGEV Purdue P115, together with the ISU-1 strain of porcine respiratory coronavirus (PRCV-ISU-1), a naturally occurring TGEV deletion mutant with an altered respiratory tropism and reduced virulence. Pairwise comparison at both the nucleotide (nt) and amino acid (aa) levels between virulent and attenuated TGEV strains identified a common change in nt 1753 of the spike gene, resulting in a serine to alanine mutation at aa position 585 of the spike proteins of the attenuated TGEV strains. Alanine was also present in this protein in PRCV-ISU-1. Particularly noteworthy, the serine to alanine mutation resides in the region of the major antigenic site A/B (aa 506-706) that elicites neutralizing antibodies and within the domain mediating the cell surface receptor aminopeptidase N binding (aa 522-744). Comparison of the predicted polypeptide products of ORF3b showed significant deletions in the naturally attenuated PRCV ISU-1 and TGEV Miller M60; these deletions occurred at a common break point, suggesting a related mechanism of recombination that may affect viral virulence or tropism. Sequence comparisons at both genomic and protein levels indicated that PRCV-ISU-1 had a closer relationship with TGEV Miller strains than Purdue strains. Phylogenetic analyses showed that virulence is an evolutionarily labile trait in TGEV and that TGEV strains as a group share a common ancestor with PRCV.


title: Will the next human influenza pandemic be caused by the virus of the avian flu A/H5N1? Arguments pro and counter

text: In 1997, the avian influenza A subtype H5N1 that caused big outbreaks of fowl pest in mass poultry farming had emerged in Hong Kong. Its spread throughout Eurasia had given rise to concerns in terms of the possible imminence of the next human influenza pandemic. In this article, epidemiological and virological arguments supporting or declining this fear are outlined and discussed with regard to viral infectivity and pathogenicity.


title: CT imaging features of 34 patients infected with COVID-19

text: OBJECTIVE: To retrospectively analyze the CT findings in patients infected with Coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: The thirty-four cases, 15 females and 19 males, with an age ranging from 7 to 88 years old, confirmed by real-time reverse-transcriptase-polymerase chain reaction (RT-PCR), were used for our study. All thin-section CT scans of the lungs were performed in all of patients. The clinical, laboratory and CT imaging were available to evaluate in all patients. RESULTS: The patients present with fever (85.29%, n = 29), cough (67.65%, n = 23), fatigue or myalgia (26.47%, n = 9), and pharyngalgia (8.82%, n = 3). The 4 patients (11.76%) with no symptoms were identified during screening for close contacts, who had typical CT findings. On initial CT scans, the bilateral lung involved was shown in 24 cases (70.59%), while 29 (82.35%) cases were distributed in peripheral. The pure ground glass opacity (GGO) was shown in 18 cases (52.94%), the GGO with consolidation was in 12 cases (35.29%), and full consolidation only in 3 cases. The lesion with air bronchogram was seen in 14 (41.18%) cases, with enlarged blood vessel in 17 (50.00%) cases, with crazy-paving pattern in 8 (23.53%) cases, with fine reticular pattern in 4 (11.77%) cases, and with intralesional vacuole sign in 6 (17.65%) cases. The pleural effusion was seen in one patient. Follow-up imaging in 19 patients during the study time window demonstrated mild, moderate or severe progression of disease, as manifested by increasing extent and density of lung opacities. CONCLUSIONS: The bilateral GGO with air bronchogram, enlarged blood vessel, fine reticular pattern, and peripheral distribution are the early CT findings of COVID-19. The crazy-paving pattern and intralesional vacuole sign are the features of progressive stage.


Aileen Joy Plant


title: Therapeutic potential of the renin angiotensin system in ischaemic stroke

text: The renin angiotensin system (RAS) consists of the systemic hormone system, critically involved in regulation and homeostasis of normal physiological functions [i.e. blood pressure (BP), blood volume regulation], and an independent brain RAS, which is involved in the regulation of many functions such as memory, central control of BP and metabolic functions. In general terms, the RAS consists of two opposing axes; the ‘classical axis’ mediated primarily by Angiotensin II (Ang II), and the ‘alternative axis’ mediated mainly by Angiotensin-(1–7) (Ang-(1–7)). An imbalance of these two opposing axes is thought to exist between genders and is thought to contribute to the pathology of cardiovascular conditions such as hypertension, a stroke co-morbidity. Ischaemic stroke pathophysiology has been shown to be influenced by components of the RAS with specific RAS receptor antagonists and agonists improving outcome in experimental models of stroke. Manipulation of the two opposing axes following acute ischaemic stroke may provide an opportunity for protection of the neurovascular unit, particularly in the presence of pre-existing co-morbidities where the balance may be shifted. In the present review we will give an overview of the experimental stroke studies that have investigated pharmacological interventions of the RAS.


title: SARS-Like Coronavirus WIV1-CoV Does Not Replicate in Egyptian Fruit Bats (Rousettus aegyptiacus)

text: Severe acute respiratory syndrome (SARS)-like WIV1-coronavirus (CoV) was first isolated from Rhinolophus sinicus bats and can use the human angiotensin converting enzyme 2 (ACE2) receptor. In the current study, we investigate the ability of WIV1-CoV to infect Rousettus aegyptiacus bats. No clinical signs were observed throughout the experiment. Furthermore, only four oropharyngeal swabs and two respiratory tissues, isolated on day 3 post inoculation, were found positive for viral RNA. Two out of twelve bats showed a modest increase in coronavirus specific antibodies post challenge. In conclusion, WIV1-CoV was unable to cause a robust infection in Rousettus aegyptiacus bats.


title: TAR-VIR: a pipeline for TARgeted VIRal strain reconstruction from metagenomic data

text: BACKGROUND: Strain-level RNA virus characterization is essential for developing prevention and treatment strategies. Viral metagenomic data, which can contain sequences of both known and novel viruses, provide new opportunities for characterizing RNA viruses. Although there are a number of pipelines for analyzing viruses in metagenomic data, they have different limitations. First, viruses that lack closely related reference genomes cannot be detected with high sensitivity. Second, strain-level analysis is usually missing. RESULTS: In this study, we developed a hybrid pipeline named TAR-VIR that reconstructs viral strains without relying on complete or high-quality reference genomes. It is optimized for identifying RNA viruses from metagenomic data by combining an effective read classification method and our in-house strain-level de novo assembly tool. TAR-VIR was tested on both simulated and real viral metagenomic data sets. The results demonstrated that TAR-VIR competes favorably with other tested tools. CONCLUSION: TAR-VIR can be used standalone for viral strain reconstruction from metagenomic data. Or, its read recruiting stage can be used with other de novo assembly tools for superior viral functional and taxonomic analyses. The source code and the documentation of TAR-VIR are available at https://github.com/chjiao/TAR-VIR. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12859-019-2878-2) contains supplementary material, which is available to authorized users.


title: Prime immunization with rotavirus VLP 2/6 followed by boosting with an adenovirus expressing VP6 induces protective immunization against rotavirus in mice

text: BACKGROUND: Rotavirus (RV) is the main cause of severe gastroenteritis in children. An effective vaccination regime against RV can substantially reduce morbidity and mortality. Previous studies have demonstrated the efficacy of virus-like particles formed by RV VP2 and VP6 (VLP2/6), as well as that of recombinant adenovirus expressing RV VP6 (rAd), in eliciting protective immunities against RV. However, the efficacy of such prime-boost strategy, which incorporates VLP and rAd in inducing protective immunities against RV, has not been addressed. We assessed the immune effects of different regimens in mice, including rAd prime-VLP2/6 boost (rAd+VLP), VLP2/6 prime-rAd boost (VLP+rAd), rAd alone, and VLP alone. RESULTS: Mice immunized with the VLP+rAd regimen elicit stronger humoral, mucosal, and cellular immune responses than those immunized with other regimens. RV challenging experiments showed that the highest reduction (92.9%) in viral shedding was achieved in the VLP+rAd group when compared with rAd+VLP (25%), VLP alone (75%), or rAd alone (40%) treatment groups. The reduction in RV shedding in mice correlated with fecal IgG (r = 0.95773, P = 0.04227) and IgA (r = 0.96137, P = 0.038663). CONCLUSIONS: A VLP2/6 prime-rAd boost regimen is effective in conferring immunoprotection against RV challenge in mice. This finding may lay the groundwork for an alternative strategy in novel RV vaccine development.


title: Coronavirus replication factories

text: This study suggests that double-membrane vesicles are the primary and likely only site of coronavirus viral RNA within the replication organelle.


docid: eaedmeze

title: Appropriate care for neonates born to mothers with COVID‐19 disease

text: The global COVID‐19 pandemic has been associated with high rates of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) transmission, morbidity and mortality in the general population. Evidence‐based guidance on caring for babies born to mothers with COVID‐19 is needed. There is currently insufficient evidence to suggest vertical transmission between mothers and their newborn infants. However, transmission can happen after birth from mothers or other carers. Based on the currently available data, prolonged skin‐to‐skin contact and early and exclusive breastfeeding remain the best strategies to reduce the risks of morbidity and mortality for both the mother with COVID‐19 and her baby.


title: IFN-α2a or IFN-β1a in combination with ribavirin to treat Middle East respiratory syndrome coronavirus pneumonia: a retrospective study

text: OBJECTIVES: Middle East respiratory syndrome coronavirus (MERS-CoV) is associated with significant mortality. We examined the utility of plasma MERS-CoV PCR as a prognostic indicator and compared the efficacies of IFN-α2a and IFN-β1a when combined with ribavirin in reducing MERS-CoV-related mortality rates. METHODS: We retrospectively analysed 32 patients with confirmed MERS-CoV infection, admitted between April 2014 and June 2014, by positive respiratory sample RT–PCR. Plasma MERS-CoV RT–PCR was performed at the time of diagnosis for 19 patients. RESULTS: The overall mortality rate was 69% (22/32). Ninety percent (9/10) of patients with positive plasma MERS-CoV PCR died compared with 44% (4/9) of those with negative plasma MERS-CoV PCR. Mortality rate in patients who received IFN-α2a was 85% (11/13) compared with 64% (7/11) in those who received IFN-β1a (P = 0.24). The mortality rate in patients with renal failure (14), including 8 on haemodialysis, was 100%. Age >50 years and diabetes mellitus were found to be significantly associated with mortality (OR = 26.1; 95% CI 3.58–190.76; P = 0.001 and OR = 15.74; 95% CI 2.46–100.67; P = 0.004, respectively). The median duration of viral shedding in patients who recovered was 11 days (range 6–38 days). Absence of fever was noted in 5/32 patients. CONCLUSIONS: Plasma MERS-CoV RT–PCR may serve as an effective tool to predict MERS-CoV-associated mortality. Older age and comorbid conditions may have contributed to the lack of efficacy of IFN-α2a or IFN-β1a with ribavirin in treating MERS-CoV. Absence of fever should not exclude MERS-CoV.


title: A brief review of interplay between vitamin D and angiotensin‐converting enzyme 2: Implications for a potential treatment for COVID‐19

text: The novel coronavirus disease 2019 (COVID‐19) is rapidly expanding and causing many deaths all over the world with the World Health Organization (WHO) declaring a pandemic in March 2020. Current therapeutic options are limited and there is no registered and/or definite treatment or vaccine for this disease or the causative infection, severe acute respiratory coronavirus 2 syndrome (SARS‐CoV‐2). Angiotensin‐converting enzyme 2 (ACE2), a part of the renin‐angiotensin system (RAS), serves as the major entry point into cells for SARS‐CoV‐2 which attaches to human ACE2, thereby reducing the expression of ACE2 and causing lung injury and pneumonia. Vitamin D, a fat‐soluble‐vitamin, is a negative endocrine RAS modulator and inhibits renin expression and generation. It can induce ACE2/Ang‐(1‐7)/MasR axis activity and inhibits renin and the ACE/Ang II/AT1R axis, thereby increasing expression and concentration of ACE2, MasR and Ang‐(1‐7) and having a potential protective role against acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Therefore, targeting the unbalanced RAS and ACE2 down‐regulation with vitamin D in SARS‐CoV‐2 infection is a potential therapeutic approach to combat COVID‐19 and induced ARDS.


title: Efficacy and safety of Chou-Ling-Dan granules in the treatment of seasonal influenza via combining Western and traditional Chinese medicine: protocol for a multicentre, randomised controlled clinical trial

text: INTRODUCTION: Chou-Ling-Dan (CLD) (Laggerapterodonta) granules are an ethnic herbal medicine from Yunnan province of China. CLD granules have been used for the treatment of inflammatory conditions and feverish diseases in China, including seasonal influenza, but few evidence-based medicine (EBM) clinical studies have been conducted to assess its efficacy and safety in the treatment of influenza. Here, we performed an EBM clinical trial combining Western Chinese medicine and traditional Chinese medicine (TCM) evaluation systems to evaluate the efficacy and safety of CLD granules in the treatment of seasonal influenza. METHODS AND ANALYSIS: The study is designed as a multicentre, randomised, double-blinded, double-simulation, oseltamivir-controlled and placebo-controlled, parallel-design clinical trial. Eligible subjects (n=318) will be allocated after satisfying the criteria (Western medicine). Subjects will be randomised to receive CLD granules, oseltamivir, or a placebo for 5 days of treatment and with follow-up after treatment to record symptoms and signs and to collect pharyngeal/throat swabs and serum samples for detecting the virus and antibodies. At the same time, the syndrome differentiation criteria of TCM, such as tongue body, furred tongue and type of pulse, will be recorded as determined by doctors of both Western and Chinese medicine. Participants will be instructed to comply with the protocol and to keep a daily record of symptoms. The primary and secondary outcomes and safety indicators will be used to evaluate the efficacy and safety of CLD granules in the treatment of seasonal influenza based on both Western Chinese medicine and TCM evaluation systems. ETHICS AND DISSEMINATION: The CLD granules clinical trial will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice and has been approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University. All participants must provide written informed consent. The results obtained will be disseminated at international medical conferences and in peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT02662426; Pre-results.


title: Causes of fever in primary care in Southeast Asia and the performance of C-reactive protein in discriminating bacterial from viral pathogens

text: Abstract Objectives We investigated causes of fever in the primary levels of care in Southeast Asia, and evaluated whether C-reactive protein (CRP) could distinguish bacterial from viral pathogens. Methods Blood and nasopharyngeal swab specimens were taken from children and adults with fever (>37.5˚C) or history of fever (<14 days) in Thailand and Myanmar. Results Of 773 patients with at least one blood or nasopharyngeal swab specimen collected, 227 (29.4%) had a target organism detected. Influenza virus type A was detected in 85/227 cases (37.5%), followed by dengue virus (30 cases, 13.2%), respiratory syncytial virus (24 cases, 10.6%) and Leptospira spp. (9 cases, 4.0%). Clinical outcome was similar between patients with a bacterial or a viral organism, regardless of antibiotic prescription. CRP was higher among patients with a bacterial organism compared to those with a viral organism (median 18mg/L, interquartile range [10-49] versus 10mg/L [≤8-22], p-value 0.003), with an area under the curve of 0.65, 95% confidence interval (0.55-0.75). Conclusions Serious bacterial infections requiring antibiotics are exceptions rather than the rule in the first lines of care. CRP-testing could assist in ruling out such cases in settings where diagnostic uncertainty is high and routine antibiotic prescription is common. The original CRP randomised-controlled trial (RCT) was registered with ClinicalTrials.gov, number NCT02758821.


title: Proteomics studies reveal important information on small molecule therapeutics: a case study on plasma proteins

text: The most abundant proteins in serum, such as albumin and IgG, act as molecular sponges that bind and transport low molecular weight proteins/peptides and drugs. In the near future, pharmacoproteomics, the use of proteomic technologies in the field of drug discovery and development, and interactomics, the branch of proteomics which is concerned with identifying interactions between proteins, will allow researchers to (i) know the specific protein changes that occur in biological compartments in response to drug administration; (ii) design small novel therapeutic molecules that can have extended half-lives if carried by plasma protein in the blood stream. Advances in these fields will open new avenues of tailor-made molecular therapy, reducing present limitations on treatment arising from toxicity and inefficiency. In this short review we report and discuss the most recent developments arising from the use of proteomic tools in blood plasma protein research, looking at the identification of proteins found in plasma as well as their interactions with small molecules such as drugs, peptides, organic chemicals and metals. We believe this research demonstrates that proteomic technologies, and in particular pharmacoproteomics, interactomics and post-translational modification analysis, could be instrumental in the design of new tailor-made drugs leading to substantial improvements in molecular therapy.


title: Analysis of morphology, nanostructure, and oxidation reaction of soot particulates from CI engines with dimethoxymethane–diesel blends under different loads and speeds

text: Dimethoxymethane (DMM)–diesel blended fuels can simultaneously reduce exhaust emissions of soot and nitrogen oxide (NO(X)); several studies have been conducted in this regard. However, the influence of additive DMM on the production of inception and precursors of particulates, especially the relation between oxidation, morphology, and the nanostructure of soot particles has not been extensively investigated. In this study, a transmission electron microscope (TEM) and a thermogravimetric analyzer are introduced to acquire TEM images and conduct temperature-programmed-oxidation experiments. Aiming to study the influence of DMM addition on soot oxidation, morphology, and nanostructure, tests are conducted at different rotational speeds (1400 rpm and 2200 rpm), two engine loads (0.6 MPa and 1.2 MPa), and three fuels (D100, DMM6.4, and DMM13). The results show that the diameter distributions of all samples display a similar distribution, with the range of sample diameters being from 10 to 45 nm, and the addition of DMM reduces the dp (primary particle diameters) and the Df (fractal dimension), indicating a decreased structural compactness of aggregates, compared with diesel. Moreover, with increasing load and speed, La (the length of the fringe) increases and d (the distance between adjacent layer planes) decreases. Furthermore, with the addition of DMM, a more regular and higher degree of graphitization within soot particles can be observed in comparison to D100. The nanostructure influences the oxidation reaction of graphene segments with a line relation, leading to a difference in soot oxidation property.


title: An overview on molecular chaperones enhancing solubility of expressed recombinant proteins with correct folding

text: Abstract The majority of research topics declared that most of the recombinant proteins have been expressed by Escherichia coli in basic investigations. But the majority of high expressed proteins formed as inactive recombinant proteins that are called inclusion body. To overcome this problem, several methods have been used including suitable promoter, environmental factors, ladder tag to secretion of proteins into the periplasm, gene protein optimization, chemical chaperones and molecular chaperones sets. Co-expression of the interest protein with molecular chaperones is one of the common methods The chaperones are a group of proteins, which are involved in making correct folding of recombinant proteins. Chaperones are divided two groups including; cytoplasmic and periplasmic chaperones. Moreover, periplasmic chaperones and proteases can be manipulated to increase the yields of secreted proteins. In this article, we attempted to review cytoplasmic chaperones such as Hsp families and periplasmic chaperones including; generic chaperones, specialized chaperones, PPIases, and proteins involved in disulfide bond formation.