title: Widening participation would be key in enhancing bioinformatics and genomics research in Africa

text: Bioinformatics and genome science (BGS) are gradually gaining roots in Africa, contributing to studies that are leading to improved understanding of health, disease, agriculture and food security. While a few African countries have established foundations for research and training in these areas, BGS appear to be limited to only a few institutions in specific African countries. However, improving the disciplines in Africa will require pragmatic efforts to expand training and research partnerships to scientists in yet-unreached institutions. Here, we discuss the need to expand BGS programmes in Africa, and propose mechanisms to do so.


title: ENTEROVIRUS D68-ASSOCIATED RESPIRATORY INFECTION IN SOUTHERN BRAZIL, 2018 – A POPULATION-BASED LABORATORY SURVEILLANCE

text: Enterovirus D68 (EV-D68) strain was confirmed in 36/69 - 52.2% of enterovirus-positive samples collected through surveillance networks for severe acute respiratory infections (SARI) and influenza-like illness (ILI) in southern Brazil in 2018. This finding settles the sustained circulation of EV-D68 in southern Brazil.


title: The Ras–PI3K Signaling Pathway Is Involved in Clathrin-Independent Endocytosis and the Internalization of Influenza Viruses

text: BACKGROUND: Influenza virus infection causes highly contagious, severe respiratory disorders and gives rise to thousands of deaths every year; however, the efficacy of currently approved defense strategies, including vaccines and neuraminidase inhibitors, is limited because the virus frequently acquires resistance via antigen drift and reassortment. It is therefore important to establish a novel, effective therapeutic strategy that is effective irrespective of viral subtype. METHODOLOGY/PRINCIPAL FINDINGS: Here, we identify the Ras–phosphoinositide 3-kinase (PI3K) signaling pathway as a host-cell regulatory mechanism for influenza virus entry. The binding of Ras to PI3K is specifically involved in clathrin-independent endocytosis, endosomal maturation, and intracellular transport of viruses, which result in decreased infectious efficacy of different subtypes of influenza viruses in cells lacking the Ras–PI3K interaction. Moreover, influenza virus infection indeed triggered Ras activation and subsequent PI3K activation in early endosomes. CONCLUSIONS/SIGNIFICANCE: Taken together, these results demonstrate that the Ras–PI3K signaling axis acts as a host-oriented mechanism for viral internalization. Given that virus incorporation is a process conserved among virus subtypes and species, this signaling pathway may provide a target for potent, well-tolerated prophylactics and therapeutics against a broad range of viruses.


title: CT manifestations and clinical characteristics of 1115 patients with coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis

text: Abstract Rationale and objectives: We aimed to assess the prevalence of significant computed tomographic(CT) manifestations and describe some notable features based on chest CT images, as well as the main clinical features of patients with coronavirus disease 2019(COVID-19). Materials and methods: A systematic literature search of PubMed, EMBASE, the Cochrane Library, and Web of Science was performed to identify studies assessing CT features, clinical and laboratory results of COVID-19 patients. A single-arm meta-analysis was conducted to obtain the pooled prevalence and 95% confidence interval(95%CI). Results: A total of 14 articles(including 1115 patients) based on chest CT images were retrieved. In the lesion patterns on chest CTs, we found that pure ground-glass opacities(GGO)(69%, 95%CI 58–80%), consolidation(47%, 35–60%) and “air bronchogram sign”(46%,25–66%) were more common than the atypical lesion of “crazy-paving pattern”(15%, 8–22%). With regard to disease extent and involvement, 70%(95%CI 46–95%) of cases showed a location preference for the right lower lobe, 65%(58–73%) of patients presented with ≥3 lobes involvement, and meanwhile, 42%(32–53%) of patients had involvement of all five lobes, while 67%(55–78%) of patients showed a predominant peripheral distribution. An understanding of some important CT features might be helpful for medical surveillance and management. In terms of clinical features, muscle soreness(21%, 95%CI 15–26%) and diarrhea(7%, 4–10%) were minor symptoms compared with fever(80%, 74–87%) and cough(53%, 33–72%). Conclusion: Chest CT manifestations in patients with COVID-19, as well as its main clinical characteristics, might be helpful in disease evolution and management.


title: COVID‐19: some clinical questions after the first four months

text: Coronavirus disease 2019 (COVID‐19) is a multiorgan disease with multiple faces and clinical features. Most patients present with none or only mild symptoms, but severe presentations with need for mechanical ventilation and high case fatality may be observed.


title: The role of high-resolution imaging in the evaluation of nanosystems for bioactive encapsulation and targeted nanotherapy

text: Abstract Nanotechnology has already started to significantly impact many industries and scientific fields including biotechnology, pharmaceutics, food technology and semiconductors. Nanotechnology-based tools and devices, including high-resolution imaging techniques, enable characterization and manipulation of materials at the nanolevel and further elucidate nanoscale phenomena and equip us with the ability to fabricate novel materials and structures. One of the most promising impacts of nanotechnology is in the area of nanotherapy. Employing nanosystems such as dendrimers, nanoliposomes, niosomes, nanotubes, emulsions and quantum dots, nanotherapy leads toward the concept of personalized medicine and the potential for early diagnoses coupled with efficient targeted therapy. The development of smart targeted nanocarriers that can deliver bioactives at a controlled rate directly to the designated cells and tissues will provide better efficacy and reduced side effects. Nanocarriers improve the solubility of bioactives and allow for the delivery of not only small-molecule drugs but also the delivery of nucleic acids and proteins. This review will focus on nanoscale bioactive delivery and targeting mechanisms and the role of high-resolution imaging techniques in the evaluation and development of nanocarriers.


title: Weight Stigma and the “Quarantine‐15”

text: The coronavirus SARS‐CoV‐2 (i.e., COVID‐19) has caused significant disruption in everyday life on a global scale. Due to stay‐at‐home orders and sudden unemployment, millions have found themselves isolated at home without their usual routines. This rise in unstructured time, combined with the enormous stress of the pandemic and its far‐reaching consequences, have led to widespread concerns among the general public about vulnerability to overeating, sedentary behavior, and weight gain. These concerns are reflected in the explosion of social media posts referencing the “quarantine‐15.”


title: Hospital-Associated Infections in Small Animal Practice

text: Hospital-associated infections (HAIs) occur in veterinary hospitals of all types and sizes, and their frequency is likely to increase. Urinary tract infections, pneumonia, bloodstream infections, surgical site infections, and infectious diarrhea are the HAIs most frequently identified in veterinary medicine. A hospital infection control program, consisting of an infectious disease control officer, written protocols, and staff training, is critical to reducing HAIs and promoting patient, staff, and client health. Infection control protocols (plans) should include discussion of hand hygiene and use of personal protective equipment, cleaning and disinfection, patient management, with-in hospital surveillance, and antimicrobial stewardship.


title: Mimicking the passage of avian influenza viruses through the gastrointestinal tract of chickens

text: Abstract In contrast to human influenza viruses that replicate in the respiratory tract and are airborne transmitted, avian viruses also replicate in gut epithelial cells and are transmitted via the fecal-oral route. On this route, the virus is exposed to destructive fluids of the digestive tract, which are acidic and contain the proteases pepsin (gizzard) or chymotrypsin and trypsin (intestine). Only the latter enzyme activates virus by cleaving hemagglutinin (HA) into HA1 and HA2 subunits. We mimicked the passage of viruses through the gastrointestinal tract by treating them with digestive fluids from chicken and determined titers and integrity of HA by western-blot. Gizzard fluid completely inactivated virions and degrades HA even at a high dilution, but only if the pH was kept acidic. If the fluid is diluted with neutral buffer (mimicking virus uptake with seawater) particles were more resistant. Virions containing an uncleaved HA were even activated suggesting that gastric juice contains a trypsin-like protease. Undiluted intestinal fluid inactivated particles and destroyed HA, but diluted fluid activated virions. A virus isolated from the duck´s intestine is more tolerant against intestinal fluid compared to fowl plague virus suggesting that the former is better adapted to grow in the intestine. We also demonstrate that influenza viruses replicate to high titers in a novel chicken epithelial gut cell line. While viruses with a monobasic HA cleavage site require addition of trypsin, these cells effectively process HA with a polybasic cleavage site, which could be blocked with an inhibitor of the cellular furin protease.


title: Points to consider in the preparation and transfusion of COVID‐19 convalescent plasma

text: This document prepared and endorsed by the Working Party on Global Blood Safety of the International Society of Blood Transfusion presents elements, as of April 2020, to take into consideration in the preparation and transfusion of COVID-19 convalescent plasma as a possible treatment approach of COVID-19. The document covers the following important factors to have in mind when considering this treatment: (a) eligibility criteria of convalescent COVID-19 patients to donate whole blood or plasma, (b) pre-screening and pre-donation testing of convalescent COVID-19 donors; (c) criteria for collection of COVID-19 plasma; (d) post-donation treatment of plasma; and (e) it offers recommendations for plasma transfusion.


title: Evolutionary origins of epidemic potential among human RNA viruses

text: To have epidemic potential, a pathogen must be able to spread in human populations, but of human-infective RNA viruses only a minority can do so. We investigated the evolution of human transmissibility through parallel analyses of 1755 virus genome sequences from 39 RNA virus genera. We identified 57 lineages containing human-transmissible species and estimated that at least 74% of these lineages have evolved directly from non-human viruses in other mammals or birds, a public health threat recently designated “Disease X”. Human-transmissible viruses rarely evolve from virus lineages that can infect but not transmit between humans. This result cautions against focussing surveillance and mitigation efforts narrowly on currently known human-infective virus lineages and supports calls for a better understanding of RNA virus diversity in non-human hosts.


title: Induction of Cell-Cell Fusion by Ebola Virus Glycoprotein: Low pH Is Not a Trigger

text: Ebola virus (EBOV) is a highly pathogenic filovirus that causes hemorrhagic fever in humans and animals. Currently, how EBOV fuses its envelope membrane within an endosomal membrane to cause infection is poorly understood. We successfully measure cell-cell fusion mediated by the EBOV fusion protein, GP, assayed by the transfer of both cytoplasmic and membrane dyes. A small molecule fusion inhibitor, a neutralizing antibody, as well as mutations in EBOV GP known to reduce viral infection, all greatly reduce fusion. By monitoring redistribution of small aqueous dyes between cells and by electrical capacitance measurements, we discovered that EBOV GP-mediated fusion pores do not readily enlarge—a marked difference from the behavior of other viral fusion proteins. EBOV GP must be cleaved by late endosome-resident cathepsins B or L in order to become fusion-competent. Cleavage of cell surface-expressed GP appears to occur in endosomes, as evidenced by the fusion block imposed by cathepsin inhibitors, agents that raise endosomal pH, or an inhibitor of anterograde trafficking. Treating effector cells with a recombinant soluble cathepsin B or thermolysin, which cleaves GP into an active form, increases the extent of fusion, suggesting that a fraction of surface-expressed GP is not cleaved. Whereas the rate of fusion is increased by a brief exposure to acidic pH, fusion does occur at neutral pH. Importantly, the extent of fusion is independent of external pH in experiments in which cathepsin activity is blocked and EBOV GP is cleaved by thermolysin. These results imply that low pH promotes fusion through the well-known pH-dependent activity of cathepsins; fusion induced by cleaved EBOV GP is a process that is fundamentally independent of pH. The cell-cell fusion system has revealed some previously unappreciated features of EBOV entry, which could not be readily elucidated in the context of endosomal entry.


title: Cancer Prevales on Covid‐19: To Maintain a High Quality Standard Concerning Diagnosis and Oncological Care Even During a Pandemic

text: recently, Yang et al(1) have analyzed retrospectively clinical characteristics and outcomes of 52 cancer patients with novel coronavirus disease‐19 (COVID‐19). They concluded that the infection rate of severe acute respiratory syndrome corona virus 2 (SARS‐CoV‐2) in cancer patients was higher than the general population, cancer patients with COVID‐19 showed deteriorating conditions and poor outcomes. This article is protected by copyright. All rights reserved.


title: The physiology and pharmacology of singlet oxygen

text: Reactive oxygen species (ROS) are generated by many different cells. Singlet oxygen (1O2) and a reaction product of it, excited carbonyls (CO(*)), are important ROS. 1O2 and CO(*) are nonradicalic and emit light (one photon/molecule) when returning to ground state oxygen. Especially activated polymorphonuclear neutrophil granulocytes (PMN) produce large amounts of 1O2. Via activation of the respiratory burst (NADPH oxidase and myeloperoxidase) they synthesize hypochlorite (NaOCl) and chloramines (in particular N-chlorotaurine). Chloramines are selective and stable chemical generators of 1O2. In the human organism, 1O2 is both a signal and a weapon with therapeutic potency against very different pathogens, such as microbes, virus, cancer cells and thrombi. Chloramines at blood concentrations between 1 and 2 mmol/L inactivate lipid enveloped virus and chloramines at blood concentrations below 0.5 mmol/L, i.e. at oxidant concentrations that do not affect thrombocytes or hemostasis factors, act antithrombotically by activation of the physiologic PMN mediated fibrinolysis; this thrombolysis is of selective nature, i.e. it does not impair the hemostasis system of the patient allowing the antithrombotic treatment in patients where the current risky thrombolytic treatment is contraindicated. The action of 1O2 might be compared to the signaling and destroying gunfire of soldiers directed against bandits at night, resulting in an autorecruitment of the physiological inflammatory response. Chloramines (such as the mild and untoxic oxidant chloramine T(®) (N-chloro-p-toluene-sulfonamide)) and their signaling and destroying reaction product 1O2 might be promising new therapeutic agents against a multitude of up to now refractory diseases.


title: Population health technologies Emerging innovations for the health of the public

text: Abstract At the beginning of the 21st century, we are at the dawn of a possibly unprecedented era of scientific discovery and promise. Emerging technologies, including information and communication technologies, genomics, microelectromechanical systems, robotics, sensors, and nanotechnologies, provide enormous opportunities for population health improvement. Population health technology refers to the application of an emerging technology to improve the health of populations. Emerging technologies present an opportunity for addressing global health challenges—in both developed and developing countries. Health issues ripe for the application of new technologies include disease surveillance and control, environmental monitoring and pollution prevention, food safety, health behavior change, self-care, population screening, and chronic disease and injury prevention and control. If appropriately applied, population health technologies may greatly enhance existing health intervention models. However, potential adverse consequences could arise related to privacy, confidentiality, and security; quality and effectiveness; sustainability; and the technology divide. To ensure the optimal development and diffusion of population health technologies will require balancing these risks and benefits while simultaneously adopting new mechanisms of public and private support for research and development in this potentially important new domain of public health.


title: Targeting host lipid flows: Exploring new antiviral and antibiotic strategies

text: Bacteria and viruses pose serious challenges for humans because they evolve continuously. Despite ongoing efforts, antiviral drugs to treat many of the most troubling viruses have not been approved yet. The recent launch of new antimicrobials is generating hope as more and more pathogens around the world become resistant to available drugs. But extra effort is still needed. One of the current strategies for antiviral and antibiotic drug development is the search for host cellular pathways used by many different pathogens. For example, many viruses and bacteria alter lipid synthesis and transport to build their own organelles inside infected cells. The characterization of these interactions will be fundamental to identify new targets for antiviral and antibiotic drug development. This review discusses how viruses and bacteria subvert cell machineries for lipid synthesis and transport and summarises the most promising compounds that interfere with these pathways.


title: Ebola and Marburg virus vaccines

text: The filoviruses, Ebola virus (EBOV), and Marburg virus (MARV), are among the most pathogenic viruses known to man and the causative agents of viral hemorrhagic fever outbreaks in Africa with case fatality rates of up to 90%. Nearly 30,000 infections were observed in the latest EBOV epidemic in West Africa; previous outbreaks were much smaller, typically only affecting less than a few hundred people. Compared to other diseases such as AIDS or Malaria with millions of cases annually, filovirus hemorrhagic fever (FHF) is one of the neglected infectious diseases. There are no licensed vaccines or therapeutics available to treat EBOV and MARV infections; therefore, these pathogens can only be handled in maximum containment laboratories and are classified as select agents. Under these limitations, a very few laboratories worldwide conducted basic research and countermeasure development for EBOV and MARV since their respective discoveries in 1967 (MARV) and 1976 (EBOV). In this review, we discuss several vaccine platforms against EBOV and MARV, which have been assessed for their protective efficacy in animal models of FHF. The focus is on the most promising approaches, which were accelerated in clinical development (phase I–III trials) during the EBOV epidemic in West Africa.


Computed tomography and point‐of‐care ultrasound findings in 2 COVID‐19 patients


title: Advances in disease diagnosis, vaccine development and other emerging methods to control pathogens in aquaculture

text: Disease is still regarded as a major constraint to aquaculture production globally. Rapid disease diagnosis and vaccination play a huge part in the control of bacterial diseases, and there has been significant progress in both of these areas. This chapter considers the limitations of existing methods and reviews recent advances made in pathogen detection technologies and vaccine development methodologies. Future directions are discussed, including nanotechnology and reversed vaccinology.


title: Screening of drugs by FRET analysis identifies inhibitors of SARS-CoV 3CL protease

text: SARS-CoV 3CL protease is essential for viral protein processing and is regarded as a good drug target to prevent SARS-CoV replication. In the present study, we established a high-throughput FRET technique for screening for anti-SARS-CoV 3CL protease drugs. Of a thousand existing drugs examined, hexachlorophene was identified as the most potent in inhibiting SARS-CoV 3CL protease. Further characterization showed that it was effective at micromolar concentrations (K(i) = 4 μM). The binding mode was competitive, and the inhibitory effect was dependent on preincubation time. Two other drugs, triclosan and nelfinavir, were about 10 times less potent. The structure-based search and biological evaluation of various hexachlorophene analogues were described. These analogues gave optimal inhibitory activity against SARS-CoV 3CL protease with IC(50) values ranging from 7.6 to 84.5 μM. Optimization of hexachlorophene analogues was shown to provide several active 3CL protease inhibitors that function as potential anti-SARS agents.


title: Structural characterization of the N‐terminal part of the MERS‐CoV nucleocapsid by X‐ray diffraction and small‐angle X‐ray scattering

text: The N protein of coronaviruses is a multifunctional protein that is organized into several domains. The N‐terminal part is composed of an intrinsically disordered region (IDR) followed by a structured domain called the N‐terminal domain (NTD). In this study, the structure determination of the N‐terminal region of the MERS‐CoV N protein via X‐ray diffraction measurements is reported at a resolution of 2.4 Å. Since the first 30 amino acids were not resolved by X‐ray diffraction, the structural study was completed by a SAXS experiment to propose a structural model including the IDR. This model presents the N‐terminal region of the MERS‐CoV as a monomer that displays structural features in common with other coronavirus NTDs.


title: Molecularly Imprinted Solid Phase Extraction using Bismethacryloyl-β-cyclodextrin and Methacrylic Acid as Double Functional Monomers for Selective Analysis of Glycyrrhizic Acid in Aqueous Media

text: In this work, a new molecularly imprinted solid phase extraction protocol was developed for the selective extraction and purification of glycyrrhizic acid from liquorice roots in aqueous media. The molecularly imprinted polymers (MIPs) for glycyrrhizic acid were prepared by using bismethacryloyl-β-cyclodextrin and methacrylic acid as double functional monomers and characterized by Fourier transform infrared spectroscopy, scanning electron microscope, thermo gravimetric analysis, nitrogen adsorption and elemental analysis. In aqueous media, the adsorption properties of MIPs including adsorption kinetics, adsorption isotherms and selectivity adsorption were investigated. The characterization of imprinted polymers indicated that the prepared MIPs had good stability and many cavity structures. The results of adsorption experiments illustrated the MIPs had high adsorption capacity of glycyrrhizic acid (69.3 mg g(−1)) with the imprinting factor 3.77, and it took ~5 min to get adsorption equilibrium. The MIPs could be used as an solid phase extraction sorbent absorbent for enrichment and purification of glycyrrhizic acid from the crude extraction of licorice roots, and the results showed promising practical value.


title: Highly pathogenic porcine reproductive and respiratory syndrome virus infection results in acute lung injury of the infected pigs

text: Abstract Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) was firstly characterized in 2006 in China. The virus has caused great economic loss to the Chinese swine production during the past years. Herein, we experimentally infected SPF pigs using two strains of PRRSV with different pathogenicity and observed the lung pathological changes looking for new sights on the possible pathogenesis associated with the virulence of HP-PRRSV. The results indicated that the HP-PRRSV-infected pigs died and exhibited severe pathological changes of lungs featuring increased neutrophils, mast cells and mononuclear macrophages, compared with the pigs inoculated with low pathogenic (LP-) PRRSV. Furthermore, the pigs infected with HP-PRRSV showed the higher levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, interleukin (IL)-8 and histamine, leukotriene B4 (LTB4), platelet activation factor (PAF) in sera than those inoculated with LP-PRRSV. Additionally, the fibrosis of lung was observed in the HP-PRRSV-infected pigs. At present, our findings suggest that the aberrant immune responses triggered by HP-PRRSV infection are closely related to acute lung injury (ALI), and especially the pathological changes in lung vascular system are of particular significance. These associated pathological changes of lung are in part responsible for the additional morbidity and mortality observed in HP-PRRSV infection.


title: Replicative virus shedding in the respiratory tract of patients with Middle East respiratory syndrome coronavirus infection

text: Abstract Background Information on the duration of replicative Middle East respiratory syndrome coronavirus (MERS-CoV) shedding is important for infection control. The detection of MERS-CoV sub-genomic mRNAs indicates that the virus is replicative. This study examined the duration for detecting MERS-CoV sub-genomic mRNA compared with genomic RNA in diverse respiratory specimens. Methods Upper and lower respiratory samples were obtained from 17 MERS-CoV-infected patients. MERS-CoV sub-genomic mRNA was detected by reverse transcription PCR (RT-PCR) and MERS-CoV genomic RNA by real-time RT-PCR. Results In sputum and transtracheal aspirate, sub-genomic mRNA was detected for up to 4 weeks after symptoms developed, which correlated with the detection of genomic RNA. In oropharyngeal and nasopharyngeal swab specimens, the detection of sub-genomic mRNA and genomic RNA did not correlate. Conclusions These findings suggest that MERS-CoV does not replicate well in the upper respiratory tract.


Occupational psychosocial risks of health professionals in the face of the crisis produced by the COVID-19: From the identification of these risks to immediate action


title: Data analysis of COVID-2019 epidemic using machine learning methods: a case study of India

text: At this time, COVID-2019 is spreading its foot in the form of a huge epidemic for the world. This epidemic is spreading its foot very fast in India too. One of the World Health Organization states that COVID-2019 is a serious disease that spreads from one person to another at very fast speed through contact routes and respiratory drops. On this day, India and the world should rise to an effective step to analyze this disease and eliminate the effects of this epidemic. In this paper presented, the growing database of COVID-2019 has been analyzed from March 1, 2020, to April 11, 2020, and the next one is predicted for the number of patients suffering from the rising COVID-2019. Different regression analysis models have been utilized for data analysis of COVID-2019 of India based on data stored by Kaggle in between 1 March 2020 to 11 April 2020. In this study, we have been utilized six regression analysis based models namely quadratic, third degree, fourth degree, fifth degree, sixth degree, and exponential polynomial respectively for the COVID-2019 dataset. We have calculated the root mean square of these six regression analysis models. In these six models, the root mean square error of sixth degree polynomial is very less in compared other like quadratic, third degree, fourth degree, fifth degree, and exponential polynomial. Therefore the sixth degree polynomial regression model is very good models for forecasting the next 6 days for COVID-2019 data analysis in India. In this study, we have found that the sixth degree polynomial regression models will help Indian doctors and the Government in preparing their plans in the next 7 days. Based on further regression analysis study, this model can be tuned for forecasting over long term intervals.


title: Incidence and implications of unrecognized viral respiratory tract infections in premature infants during their birth hospitalization: a prospective surveillance study in two neonatal intensive care units

text: OBJECTIVE: We sought to determine the frequency and effects of nosocomial respiratory viral infections (RVIs) in premature neonates, including those who may be asymptomatic. STUDY DESIGN: We performed a year-long surveillance for RVIs in infants <33 weeks gestational age admitted to two Syracuse neonatal intensive care units (NICUs). Infants were enrolled within 3 days of NICU admission and were sampled for RVIs until discharge using a multiplex PCR assay capable of detecting 17 different respiratory viruses or subtypes. RESULTS: 26 of 50 prematurely born infants (52%) tested positive for a respiratory virus at least once during their birth hospitalization. Testing positive for a respiratory virus was significantly associated with longer length of stay (70 days vs. 35 days, p = 0.002) and prolonged ventilatory support (51 vs. 13 days, p = 0.002). Infants who tested positive for a respiratory virus during their birth hospitalization had more than twice the rate of developing bronchopulmonary dysplasia (BPD; p < 0.05). CONCLUSION: Nosocomial RVIs were frequent in our study population, despite the absence of clinical indicators of illness. Length of hospital stay was significantly longer and a diagnosis of BPD was more common in those premature infants who had respiratory viruses detected.


title: Serum Cytokine and Chemokine Profile in Relation to the Severity of Coronavirus Disease 2019 in China

text: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We investigated the serum cytokine and chemokine levels in asymptomatic, mild, moderate, severe, and convalescent SARS-CoV-2–infected cases. Proinflammatory cytokine and chemokine production induced by SARS-CoV-2 were observed not only in symptomatic patients but also in asymptomatic cases, and returned to normal after recovery. IL-6, IL-7, IL-10, IL-18, G-CSF, M-CSF, MCP-1, MCP-3, IP-10, MIG, and MIP-1α were found to be associated with the severity of COVID-19. Moreover, a set of cytokine and chemokine profiles were significantly higher in SARS-CoV-2–infected male than female patients. The serum levels of MCP-1, G-CSF, and VEGF were weakly and positively correlated with viral titers. We suggest that combinatorial analysis of serum cytokines and chemokines with clinical classification may contribute to evaluation of the severity of COVID-19 and optimize the therapeutic strategies.


title: Etiology and Clinical Characteristics of Influenza-Like Illness (ILI) in Outpatients in Beijing, June 2010 to May 2011

text: BACKGROUND: Since May 2009, exposure of the population of Beijing, China to pH1N1 has resulted in an increase in respiratory illnesses. Limited information is available on the etiology and clinical characteristics of the influenza-like illness (ILI) that ensued in adults following the pH1N1 pandemic. METHODS: Clinical and epidemiological data of ILI in adults was collected. A total of 279 throat swabs were tested for twelve respiratory viruses using multiplex RT-PCR. Clinical characteristics of influenza A in outpatients versus test-negative patients were compared using Pearson's χ2 and the Mann-Whitney U test. 190 swabs were tested for pH1N1 by virus isolation. Consultation rates for ILI were compared between 2009 and 2010. RESULTS: One or two virus were detected in 29% of the samples. Influenza A virus (FLU-A) accounted for 22.9% (64/279). Other viruses were present at a frequency less than 3.0%. Cough was significantly associated with Influenza A virus infection (χ2, p<0.001). The positive rate of FLU-A was consistent with changes in the ILI rate during the same period and there was a significant reduction in the incidence of ILI in 2010 when compared to 2009. During the 2010–2011 influenza season, the incidence peaked in January 2011 in Beijing and north China. CONCLUSIONS: Exposure to pH1N1 had no impact on typical influenza seasonal peaks, although FLU-A remained the predominant virus for 2010 in Beijing. Symptomatically, cough was associated with FLU-A infection. The positive rate of influenza virus was consistent with changes in the ILI rate during the same period and there was a significant reduction in the incidence of ILI in 2010 when compared to that of 2009.


title: Avian influenza in human in Nepal: timely management and preparedness

text: Avian influenza virus infection in humans is an emerging zoonotic disease having high economic and public health impacts. Due to its capability for genetic re-assortment, this virus can emerge as novel influenza strains with pandemic potential. Even though the first Avian influenza incidence in humans in Nepal was reported in April 2019, the threat of the disease remains unmitigated. Limited resources for surveillance, disease tracking, and weak health care facilities in low and middle-income countries will increase the possibility of the outbreak. Therefore, timely management and preparedness by strengthening veterinary and medical services, operational capabilities of laboratories, and surveillance programs through the "One-Health" approach could be crucial for the control of possible outbreaks in Nepal.


title: Nanomaterial-based biosensors for detection of pathogenic virus

text: Abstract Viruses are real menace to human safety that cause devastating viral disease. The high prevalence of these diseases is due to improper detecting tools. Therefore, there is a remarkable demand to identify viruses in a fast, selective and accurate way. Several biosensors have been designed and commercialized for detection of pathogenic viruses. However, they present many challenges. Nanotechnology overcomes these challenges and performs direct detection of molecular targets in real time. In this overview, studies concerning nanotechnology-based biosensors for pathogenic virus detection have been summarized, paying special attention to biosensors based on graphene oxide, silica, carbon nanotubes, gold, silver, zinc oxide and magnetic nanoparticles, which could pave the way to detect viral diseases and provide healthy life for infected patients.


Cohort Profile: The Bern Infant Lung Development Cohort


title: Association between Serum Angiotensin-converting Enzyme 2 Level with Postoperative Morbidity and Mortality after Major Pulmonary Resection in Non-small Cell Lung Cancer Patients

text: Background To explore the association between serum angiotensin-converting enzyme 2 (ACE2) levels and postoperative morbidity and mortality after major pulmonary resection in non-small cell lung cancer (NSCLC) patients. Methods Preoperative and postoperative serum ACE2 levels in 320 NSCLC patients who underwent major pulmonary resection were measured. The serum ACE2 levels on postoperative day 1 were divided into quartile categories. Results After adjustment for age, sex, body mass index, current smoking status, forced expiratory volume in 1 second, coronary heart disease, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, and tumour clinical stages, the risk of developing postoperative morbidities was significantly higher in the lowest serum ACE2 level quartile than in the highest quartile (hazard ratio, 2.12; 95% CI, 1.57-6.23; p=0.008). NSCLC patients with a serum ACE2 level ≤3.21 ng/mL had significantly higher rates of pneumonia, pleural effusion, atrial fibrillation as well as higher in-hospital mortality after major pulmonary resection, compared with those with a serum ACE2 level >3.21ng/mL. Conclusions The serum ACE2 level one day post surgery is an independent risk factor for postoperative morbidities after major pulmonary resection in NSCLC patients. Thus, it could be used as a prognostic factor for postoperative morbidities after major pulmonary resection in NSCLC patients.


title: 2-Aminopyrimidine based 4-aminoquinoline anti-plasmodial agents. Synthesis, biological activity, structure–activity relationship and mode of action studies

text: 2-Aminopyrimidine based 4-aminoquinolines were synthesized using an efficacious protocol. Some of the compounds showed in vitro anti-plasmodial activity against drug-sensitive CQ(S) (3D7) and drug-resistant CQ(R) (K1) strains of Plasmodium falciparum in the nM range. In particular, 5-isopropyloxycarbonyl-6-methyl-4-(2-nitrophenyl)-2-[(7-chloroquinolin-4-ylamino)butylamino] pyrimidine depicted the lowest IC(50) (3.6 nM) value (56-fold less than CQ) against CQ(R) strain. Structure–activity profile and binding with heme, μ-oxo-heme have been studied. Binding assays with DNA revealed better binding with target parasite type AT rich pUC18 DNA. Most compounds were somewhat cytotoxic, but especially cytostatic. Molecular docking analysis with Pf DHFR allowed identification of stabilizing interactions.


title: Transmissible gastroenteritis virus and porcine epidemic diarrhoea virus infection induces dramatic changes in the tight junctions and microfilaments of polarized IPEC-J2 cells

text: Abstract Viral infection converts the normal constitution of a cell to optimise viral entry, replication, and virion production. These conversions contain alterations or disruptions of the tight and adherens junctions between cells as part of their pathogenesis, and reorganise cellular microfilaments that initiate, sustain and spread the viral infections and so on. Using porcine epidemic diarrhoea virus (PEDV), transmissible gastroenteritis virus (TGEV) and a model of normal intestinal epithelial cells (IPEC-J2), we researched the interaction between tight and adherens junctions and microfilaments of IPEC-J2 cells with these viruses. In our work, the results showed that IPEC-J2 cells were susceptible to TGEV and PEDV infection. And TGEV could impair the barrier integrity of IPEC-J2 cells at early stages of infection through down-regulating some proteins of tight and adherens junctions, while PEDV cloud cause a slight of damage in the integrity of epithelial barrier. In addition, they also could affect the microfilaments remodelling of IPEC-J2 cells, and the drug-interfered microfilaments could inhibit viral replication and release. Furthermore, PEDV+TGEV co-infection was more aggravating to damage of tight junctions and remodelling of microfilaments than their single infection. Finally, the PEDV and TGEV infection affected the MAPK pathway, and inhibition of MAPK pathway regulated the changes of tight junctions and microfilaments of cells. These studies provide a new insight from the perspective of the epithelial barrier and microfilaments into the pathogenesis of PEDV and TGEV.


title: Novel Insights Into Immune Systems of Bats

text: In recent years, viruses similar to those that cause serious disease in humans and other mammals have been detected in apparently healthy bats. These include filoviruses, paramyxoviruses, and coronaviruses that cause severe diseases such as Ebola virus disease, Marburg haemorrhagic fever and severe acute respiratory syndrome (SARS) in humans. The evolution of flight in bats seem to have selected for a unique set of antiviral immune responses that control virus propagation, while limiting self-damaging inflammatory responses. Here, we summarize our current understanding of antiviral immune responses in bats and discuss their ability to co-exist with emerging viruses that cause serious disease in other mammals. We highlight how this knowledge may help us to predict viral spillovers into new hosts and discuss future directions for the field.


title: Development of a Genetically–Engineered, Candidate Polio Vaccine Employing the Self–Assembling Properties of the Tobacco Mosaic Virus Coat Protein

text: A synthetic gene coding for the coat protein of tobacco mosaic virus (TMVCP) was expressed in E. coli under the direction of the lacUV5 promoter. Modification of the 3′ end of the TMVCP gene by insertion of a region coding for an antigenic epitope from poliovirus type 3 resulted in the production of a hybrid TMVCP (TMVCP–polio 3). Both the E. coli–produced TMVCP and TMVCP–polio 3 were shown to assemble into virus–like rods under acidic conditions in E. coli extracts. Their purification was accomplished in a single step by chromatography on Sepharose 6B. TMVCP–polio 3 induced the formation of poliovirus neutralizing antibodies following injection into rats. The level of immune response was related to the degree of polymerization of the TMVCP–polio 3 preparations.


title: Systems kinomics for characterizing host responses to high-consequence pathogens at the NIH/NIAID Integrated Research Facility-Frederick

text: Currently, there is a paucity of information regarding the molecular pathogenesis for many high-consequence pathogens (HCPs) that pose threats to both national and international public health. In spite of this, investigations of the molecular pathogenesis for many HCPs have been limited to gross pathological changes in animal models or global analysis of gene expression. Further, questions remain regarding the ability of animal models of disease to recapitulate human molecular pathogenesis or act as predictors of therapeutic efficacy. Thus, it is likely that medical countermeasure development for HCPs will rely on identifying therapeutic targets that are uniquely modulated during HCP infection. It is also appreciated that many cellular processes can be regulated independently of changes in transcription or translation through phosphorylation events. Cellular kinases, individually or collectively (the kinome), play critical roles in regulating complex biology, underlie various malignancies, and represent high-priority drug targets. The growing interest in kinases in both basic and translational research has driven efforts to develop technologies that enable characterization of phosphorylation-mediated signal transduction. To this end, enhanced technical capabilities at the IRF-Frederick provide the unique capability for characterizing host responses to HCP insult during the course of infection and identify novel targets for therapeutic intervention.


Corona pandemic—let us not be part of the problem


title: Objective validation of YouTube™ educational videos for the instruction of regional anesthesia nerve blocks: a novel approach

text: BACKGROUND: YouTube™ (“YouTube”) is often used as an educational tool to instruct anesthesia providers on regional anesthesia nerve blocks. However, there is no current objective standard to assess the educational quality of these user-uploaded videos. A new approach was used to objectively validate these videos by comparing them to high quality educational sources for the seven most commonly used nerve blocks. OBJECTIVE: We sought to evaluate the educational quality of user-uploaded videos when compared to the highest quality anesthesia society websites (NYSORA, ACEP, USRA). METHODS: After reviewing the instructional material available for the seven most frequently conducted nerve blocks on high-quality reference websites, we documented the educational characteristics present including such things as indications, volume, anatomy, etc. Next we reviewed the five most popular videos on YouTube for each block (by views) and documented the presence or absence of these educational characteristics. RESULTS: Eighteen educational characteristics were documented in the “high-quality” anesthesia society reference material. Correlation was sought between this material and YouTube videos. Although there were varying degrees of correlation between the high quality sources and the videos, rarely did YouTube videos contain as high a percentage of these educational characteristics as the well-established sources. Some videos contained very few of these important educational characteristics. CONCLUSION: Although YouTube has been used an educational tool, we recommend that only high quality sources be used to teach or illustrate regional anesthesia nerve blocks.


title: Gel-Filtration Chromatography

text: Gel-filtration chromatography is a popular and versatile technique that permits the effective separation of proteins and other biological molecules in high yield. Here, the basis of the method is described and typical matrix types are contrasted. The selection of suitable operating conditions and applications of the method are also discussed.


title: Koch's postulates fulfilled for SARS virus

text: Severe acute respiratory syndrome (SARS) has recently emerged as a new human disease, resulting globally in 435 deaths from 6,234 probable cases (as of 3 May 2003). Here we provide proof from experimental infection of cynomolgus macaques (Macaca fascicularis) that the newly discovered SARS-associated coronavirus (SCV) is the aetiological agent of this disease. Our understanding of the aetiology of SARS will expedite the development of diagnostic tests, antiviral therapies and vaccines, and may allow a more concise case definition for this emerging disease. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/423240a) contains supplementary material, which is available to authorized users.


title: Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol

text: As of September 30, 2015, a total of 1589 laboratory-confirmed cases of infection with the Middle East respiratory syndrome coronavirus (MERS-CoV) have been reported to the World Health Organization (WHO). At present there is no effective specific therapy against MERS-CoV. The use of convalescent plasma (CP) has been suggested as a potential therapy based on existing evidence from other viral infections. We aim to study the feasibility of CP therapy as well as its safety and clinical and laboratory effects in critically ill patients with MERS-CoV infection. We will also examine the pharmacokinetics of the MERS-CoV antibody response and viral load over the course of MERS-CoV infection. This study will inform a future randomized controlled trial that will examine the efficacy of CP therapy for MERS-CoV infection. In the CP collection phase, potential donors will be tested by the enzyme linked immunosorbent assay (ELISA) and the indirect fluorescent antibody (IFA) techniques for the presence of anti-MERS-CoV antibodies. Subjects with anti-MERS-CoV IFA titer of ≥1:160 and no clinical or laboratory evidence of MERS-CoV infection will be screened for eligibility for plasma donation according to standard donation criteria. In the CP therapy phase, 20 consecutive critically ill patients admitted to intensive care unit with laboratory-confirmed MERS-CoV infection will be enrolled and each will receive 2 units of CP. Post enrollment, patients will be followed for clinical and laboratory outcomes that include anti-MERS-CoV antibodies and viral load. This protocol was developed collaboratively by King Abdullah International Medical Research Center (KAIMRC), Gulf Cooperation Council (GCC) Infection Control Center Group and the World Health Organization—International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC-WHO) MERS-CoV Working Group. It was approved in June 2014 by the Ministry of the National Guard Health Affairs Institutional Review Board (IRB). A data safety monitoring board (DSMB) was formulated. The study is registered at http://www.clinicaltrials.gov (NCT02190799).


title: What happened to blood substitutes?

text: Abstract Concerns about the safety and adequacy of the blood supply have fostered twenty years of research into the so-called “blood substitutes” among them the oxygen carriers based on modified hemoglobin. Although none of these materials has yet been licensed for use in North America or Europe, the results of research and clinical trials have increased our understanding of oxygen delivery and its regulation. In particular, the examination of the basis for the vasoactivity observed with some of the hemoglobin based oxygen carriers has led to the insight that several colligative properties of hemoglobin solutions, such as their diffusion coefficient for oxygen, viscosity and colloid oncotic pressure, are important determinants of efficacy.


title: Genomes and seroprevalence of severe fever with thrombocytopenia syndrome virus and Nairobi sheep disease virus in Haemaphysalis longicornis ticks and goats in Hubei, China

text: Abstract Ticks are medically-important arthropods that maintain and transmit numerous emerging viruses. China suffers severely from tick-borne viral diseases such as tick-borne encephalitis and severe fever with thrombocytopenia syndrome (SFTS), but the background of tick-borne viruses is very limited. Here we report the virome profiling of ticks and goat sera from SFTS-epidemic areas, and serological investigation of SFTS virus (SFTSV) and Nairobi sheep disease virus (NSDV). Results revealed divergent viruses in ticks and goat sera, including SFTSV and NSDV. Sequence and phylogenetic analyses showed that the SFTSV identified here was most closely related to human SFTSV in sampling and surrounding areas, and the NSDV to the previously identified NSDV from northeast China. Serological investigation of SFTSV infection in goats revealed intensive activity in those areas. Surprisingly, two different methods of NSDV serological investigation showed no sera positive for this virus.


title: Isolation and molecular characterization of Sul/01/09 avian infectious bronchitis virus, indicates the emergence of a new genotype in the Middle East

text: Abstract Infectious bronchitis virus (IBV) was isolated from trachea and kidney tissues of eight broiler farms in Kurdistan region of North Iraq from 2008 to 2010. The birds were suffering from respiratory and nephropathological symptoms and lesions. A 1116bp hyper mutable spike glycoprotein (S1) gene was amplified and sequenced using conventional RT-PCR. Sequence analysis and BLAST homology search in GenBank data base indicate that two of the farms were infected with the 4/91 strain, one with an unidentified IBV and five were infected with Sul/01/09. The birds in the latter five farms were suffering from nephropathogenic lesions, however, the virus was isolated from kidney but not from trachea in these cases. The birds were vaccinated regularly with 4/91 or MA5 vaccine. The deduced amino acid sequence of the isolated and amplified S1 subunit (372 aa) of Sul/01/09 was differed in 27–28% from that of all three vaccine strains (4/91, MA5, and H120) used in the region. This dissimilarity is most likely the cause of poor efficacy of vaccines used in the region, at least in five of these farms. Amino acid sequence comparison and phylogenetic tree analysis with other published IBV genotypes indicate that this newly isolated virus together with other regionally related and recently published isolates from Israel (IS/720/99, IS/885) and Egypt (egypt/Benisuef/01) belong to a new genotype. This is the first report of identification and genotyping of IBV isolate in Iraq, which indicate the circulation of 4/91 along with a new variant (Sul/01/09) of IBV in vaccinated broiler farms.


title: Recomendaciones para el manejo de la faringoamigdalitis aguda del adulto

text: Resumen La faringoamigdalitis aguda (FAA) en el adulto es una de las enfermedades infecciosas más comunes en la consulta del médico de familia. La etiología más frecuente es viral. Dentro de la etiología bacteriana, el principal agente responsable es Streptococcus pyogenes o estreptococo β-hemolítico del grupo A (EBHGA), causante del 5-30% de los casos. En el manejo diagnóstico, las escalas de valoración clínica para predecir la posible etiología bacteriana, son una buena ayuda para seleccionar a qué pacientes se deben practicar las técnicas de detección rápida de antígeno estreptocócico. Es conocido que, en general, sin estas técnicas se tiende al sobrediagnóstico de FAA estreptocócica, con la consiguiente prescripción innecesaria de antibióticos, muchas veces de amplio espectro. Así, con el manejo de las escalas y la técnica de diagnóstico rápido, elaboramos los algoritmos de manejo de la FAA. Los objetivos del tratamiento son acelerar la resolución de los síntomas, reducir el tiempo de contagio y prevenir las complicaciones supurativas locales y no supurativas. Los antibióticos de elección para el tratamiento de la FAA estreptocócica son penicilina y amoxicilina. La asociación de amoxicilina y clavulánico no está indicada en el tratamiento inicial en la infección aguda. Los macrólidos tampoco son un tratamiento de primera elección; su uso debe reservarse para pacientes con alergia a la penicilina. Es importante en nuestro país adecuar tanto el diagnóstico de la FAA bacteriana y la prescripción de antibióticos a la evidencia científica disponible. La implantación de protocolos de actuación en las farmacias comunitarias puede ser de utilidad para identificar y cribar los casos que no requieran tratamiento antibiótico. Abstract Acute pharyngitis in adults is one of the most common infectious diseases seen in general practitioners’ consultations. Viral aetiology is the most common. Among bacterial causes, the main agent is Streptococcus pyogenes or group A β-haemolytic streptococcus (GABHS), which causes 5%-30% of the episodes. In the diagnostic process, clinical assessment scales can help clinicians to better predict suspected bacterial aetiology by selecting patients who should undergo a rapid antigen detection test. If these techniques are not performed, an overdiagnosis of streptococcal pharyngitis often occurs, resulting in unnecessary prescriptions of antibiotics, most of which are broad spectrum. Consequently, management algorithms that include the use of predictive clinical rules and rapid tests have been set up. The aim of the treatment is speeding up symptom resolution, reducing the contagious time span and preventing local suppurative and non-suppurative complications. Penicillin and amoxicillin are the antibiotics of choice for the treatment of pharyngitis. The association of amoxicillin and clavulanate is not indicated as the initial treatment of acute infection. Neither are macrolides indicated as first-line therapy; they should be reserved for patients allergic to penicillin. The appropriate diagnosis of bacterial pharyngitis and proper use of antibiotics based on the scientific evidence available are crucial. Using management algorithms can be helpful in identifying and screening the cases that do not require antibiotic therapy.


title: COVID19, the pandemic which may exemplify a need for harm-reduction approaches to eating disorders: a reflection from a person living with an eating disorder

text: This reflective piece, written by a woman with an eating disorder aims to identify the impact of COVID-19 on persons living with eating disorders and provide a social justice approach as a resolution. The author identifies that eating disorder behaviors may be the only coping tool available for many persons with eating disorders during this time of uncertainty. While she acknowledges the risks associated with eating disorder behaviors, she identifies that this time of uncertainty may be a time to embrace harm-reduction in approaching the health and wellness of persons with eating disorders.


title: Practical use of povidone‐iodine antiseptic in the maintenance of oral health and in the prevention and treatment of common oropharyngeal infections

text: AIMS: To better inform medical practitioners on the role of antiseptics in oropharyngeal health and disease, this article focuses on povidone‐iodine (PVP‐I), an established and widely‐available antiseptic agent. METHODOLOGY: Review of the anti‐infective profile, efficacy and safety of PVP‐I in managing common upper respiratory tract infections such as the common cold, influenza and tonsillo‐pharyngitis, as well as oral complications resulting from cancer treatment (oral mucositis), and dental conditions (periodontitis, caries). RESULTS: Antiseptics with broad‐spectrum anti‐infective activity and low resistance potential offer an attractive option in both infection control and prevention. While there is some evidence of benefit of antiseptics in a variety of clinical settings that include dental and oral hygiene, dermatology, oncology, and pulmonology, there appears to be discordance between the evidence‐base and practice. This is especially apparent in the management and prevention of oropharyngeal infections, for which the use of antiseptics varies considerably between clinical practices, and is in marked contrast to their dermal application, where they are extensively used as both a prophylaxis and a treatment of skin and wound infections, thus minimising the use of antibiotics. CONCLUSION: The link between oral and oropharyngeal health status and susceptibility to infection has long been recognised. The high rates of antibiotic misuse and subsequent development of bacterial resistance (e.g. increasing vancomycin‐resistant enterococci (VRE) and methicillin‐resistant Staphylococcus aureus (MRSA)) in large parts of the world, especially across Asia Pacific, highlight the need for identifying alternative antimicrobials that would minimise the use of these medications. This, together with recent large‐scale outbreaks of, for example, avian and swine influenza virus, further underline the importance of an increasing armamentarium for infection prevention and control.


title: A War on Two Fronts: Cancer Care in the Time of COVID-19

text: Initial reports suggest that COVID-19 can be particularly lethal in patients with cancer. This commentary discusses how to balance a delay in cancer diagnosis or treatment against the risk for a potential COVID-19 exposure, mitigate the risks for significant care disruptions associated with social distancing behaviors, and manage the appropriate allocation of limited health care resources in this unprecedented time of health care crisis.


title: Travel and public health

text: Summary Increasing international travel and migration can interfere with public health in both the country of destination and back home. The revised International Health Regulations (IHR) and travel disease sentinel networks are means to protect public and individual health. Public health risks related to infectious disease are higher in mass gatherings, in travellers visiting friends and relatives and in sexual encounters away from home. In contrast, in-flight transmission of infections plays only a limited role.


title: Interplay between co-divergence and cross-species transmission in the evolutionary history of bat coronaviruses

text: Abstract Coronaviruses (CoVs) have been documented in almost every species of bat sampled. Bat CoVs exhibit both extensive genetic diversity and a broad geographic range, indicative of a long-standing host association. Despite this, the respective roles of long-term virus-host co-divergence and cross-species transmission (host-jumping) in the evolution of bat coronaviruses are unclear. Using a phylogenetic approach we provide evidence that CoV diversity in bats is shaped by both species richness and their geographical distribution, and that CoVs exhibit clustering at the level of bat genera, with these genus-specific clusters largely associated with distinct CoV species. Co-phylogenetic analyses revealed that cross-species transmission has been more common than co-divergence across coronavirus evolution as a whole, and that cross-species transmission events were more likely between sympatric bat hosts. Notably, however, an analysis of the CoV RNA polymerase phylogeny suggested that many such host-jumps likely resulted in short-term spill-over infections, with little evidence for sustained onward transmission in new co-roosting host species.


title: Compliance with international guidelines in adults with encephalitis

text: Abstract Background Encephalitis is associated with significant neurological disability and mortality. Many guidelines are published for encephalitis management but compliance with them is unknown. Objectives To evaluate the appropriate management and compliance to the current guidelines in adults with encephalitis. Study design A retrospective multicenter study at 17 hospitals in the Greater Houston area from August 1, 2008 through September 30, 2017. All cases met the definition for possible or probable encephalitis as per the international encephalitis consortium guidelines. Results A total of 241 adults (age >17 years) with encephalitis were enrolled. The most common etiologies were unknown (41.9 %), viral (27.8 %) and autoimmune (21.2 %). An adverse clinical outcome was seen in 49 % with 12.4 % in hospital mortality. A high compliance with guidelines (>90 %) was only seen in obtaining a brain computerized tomography (CT) scan, blood cultures and cerebrospinal fluid (CSF) gram stain and culture. A CSF herpes virus simplex (HSV) polymerase chain reaction (PCR) was done in 84 % and only repeated in 14.2 % of patients with an initial negative result. Furthermore, only two-thirds of patients were started empirically on intravenous acyclovir and antibiotics. Evaluation for other etiologies were not uniformly performed: arboviral serologies (57.3 %), CSF anti-N-Methyl-d-Aspartate Receptor (NMDA) receptor antibody (35.7 %), and CSF varicella zoster virus (VZV) PCR (32 %). The highest yield for the tests were arboviral serologies (42 %), anti-NMDA antibodies (41.2 %) and VZV PCR (16.4 %). Conclusion The management of encephalitis as per current guidelines is suboptimal leading to underutilization of currently available diagnostic tests and empirical therapy.


title: Revisión Narrativa Sobre La Respuesta Inmunitaria Frente A Coronavirus: Descripción General, Aplicabilidad Para Sars-Cov2 E Implicaciones Terapéuticas

text: Abstract The new coronavirus (SARS-CoV2) that causes a severe acute respiratory syndrome emerged in Wuhan, China, in December 2019. It produces the aforementioned disease due to coronavirus 2019 (COVID-19), and has led to a declaration of a world public health emergency by the World Health Organisation. This new SARS-CoV2 virus could share characteristics and an immune response similar to those described for other coronavirus. Given its activity on the interferon pathway, and the manner in which it dysregulates innate immunity, the use of treatments directed at modulating or containing this could be of interest. A narrative review was made of the current evidence about immunity against coronavirus and it applicability to SARS-CoV2. The physiopathogenesis is also described, along with the underlying leucocyte activity, with the intention of clarifying the possible usefulness of inflammatory biomarkers and the development of personalised treatments.


title: Impact of COVID‐19 on liver transplantation in Europe: Alert from an early survey of European Liver and Intestine Transplantation Association (ELITA) and European Liver Transplant Registry (ELTR)

text: There are scarce data on the impact of COVID‐19 pandemic on liver transplantation (LT) in Europe. The aim of this study was to obtain a preliminary data on incidence, management and outcome of COVID‐19 in liver transplant recipients and candidates in Europe. An internet‐based survey was sent to the centers affiliated with ELTR. 109 out of 149 (73%) of ELTR centers located in 28 European countries (93%) responded. 94 (86%) of the centers tested all donors and 75 (69%) centers tested all LT recipients for SARS‐Cov‐2. 73 (67%) centers selected recipients for LT in the COVID‐19 pandemic, whereas 33% did not. Eighty‐eight centers reported COVID‐19 infection in 57 LT candidates and in 272 LT recipients. Overall crude incidence of COVID‐19 among LT candidates and recipients was estimated 1.05 % (range 0.5%‐20% and 0.34% (range 0.1%‐4.8%), respectively and it was significantly higher among candidates (p<0.001). Crude rate of death was 18% (10/57) among candidates and 15% (36/244) among recipients. This first large‐scale European snapshot study clearly shows that both LT candidates and recipients are at a high risk for COVID‐19. These results plead for an early and pro‐active screening of COVID‐19 symptoms in these populations.


title: Modern Plasma Fractionation

text: Protein products fractionated from human plasma are an essential class of therapeutics used, often as the only available option, in the prevention, management, and treatment of life-threatening conditions resulting from trauma, congenital deficiencies, immunologic disorders, or infections. Modern plasma product production technology remains largely based on the ethanol fractionation process, but much has evolved in the last few years to improve product purity, to enhance the recovery of immunoglobulin G, and to isolate new plasma proteins, such as α1-protease inhibitor, von Willebrand factor, and protein C. Because of the human origin of the starting material and the pooling of 10000 to 50000 donations required for industrial processing, the major risk associated to plasma products is the transmission of blood-borne infectious agents. A complete set of measures—and, most particularly, the use of dedicated viral inactivation and removal treatments—has been implemented throughout the production chain of fractionated plasma products over the last 20 years to ensure optimal safety, in particular, and not exclusively, against HIV, hepatitis B virus, and hepatitis C virus. In this review, we summarize the practices of the modern plasma fractionation industry from the collection of the raw plasma material to the industrial manufacture of fractionated products. We describe the quality requirements of plasma for fractionation and the various treatments applied for the inactivation and removal of blood-borne infectious agents and provide examples of methods used for the purification of the various classes of plasma protein therapies. We also highlight aspects of the good manufacturing practices and the regulatory environment that govern the whole chain of production. In a regulated and professional environment, fractionated plasma products manufactured by modern processes are certainly among the lowest-risk therapeutic biological products in use today.


title: Assortativity and the Probability of Epidemic Extinction: A Case Study of Pandemic Influenza A (H1N1-2009)

text: Unlike local transmission of pandemic influenza A (H1N1-2009), which was frequently driven by school children, most cases identified in long-distance intranational and international travelers have been adults. The present study examines the relationship between the probability of temporary extinction and the age-dependent next-generation matrix, focusing on the impact of assortativity. Preferred mixing captures as a good approximation the assortativity of a heterogeneously mixing population. We show that the contribution of a nonmaintenance host (i.e., a host type which cannot sustain transmission on its own) to the risk of a major epidemic is greatly diminished as mixing patterns become more assortative, and in such a scenario, a higher proportion of non-maintenance hosts among index cases elevates the probability of extinction. Despite the presence of various other epidemiological factors that undoubtedly influenced the delay between first importations and the subsequent epidemic, these results suggest that the dominance of adults among imported cases represents one of the possible factors explaining the delays in geographic spread observed during the recent pandemic.


title: Early IFN type I response: Learning from microbial evasion strategies

text: Abstract Type I interferon (IFN) comprises a class of cytokines first discovered more than 50 years ago and initially characterized for their ability to interfere with viral replication and restrict locally viral propagation. As such, their induction downstream of germ-line encoded pattern recognition receptors (PRRs) upon recognition of pathogen-associated molecular patterns (PAMPs) is a hallmark of the host antiviral response. The acknowledgment that several PAMPs, not just of viral origin, may induce IFN, pinpoints at these molecules as a first line of host defense against a number of invading pathogens. Acting in both autocrine and paracrine manner, IFN interferes with viral replication by inducing hundreds of different IFN-stimulated genes with both direct anti-pathogenic as well as immunomodulatory activities, therefore functioning as a bridge between innate and adaptive immunity. On the other hand an inverse interference to escape the IFN system is largely exploited by pathogens through a number of tactics and tricks aimed at evading, inhibiting or manipulating the IFN pathway, that result in progression of infection or establishment of chronic disease. In this review we discuss the interplay between the IFN system and some selected clinically important and challenging viruses and bacteria, highlighting the wide array of pathogen-triggered molecular mechanisms involved in evasion strategies.


title: Feline uveitis An ‘intraocular lymphadenopathy’

text: Practical relevance Feline uveitis can be a subtle, insidious, painful, vision-threatening disease with causes that can sometimes be fatal. It is essential that clinicians remain alert to its various clinical presentations, thoroughly diagnose cases once detected, and treat the primary cause whenever possible. Clinical challenges In the majority of patients, a cause is not found and aggressive immunomodulating therapy of what may become a chronic or recurrent immune-mediated disease must be instigated. As with immune-mediated disease elsewhere, this involves local or systemic immunosuppression with slow tapering and frequent monitoring. The aim of this review is to aid diagnosis and therapy of uveitis by likening it to inflammation elsewhere (because it is more similar than it is different) while highlighting differences (because these are helpful). Global importance Feline uveitis is similar in its presentation throughout the world. Although the list of infectious causes may vary in composition or order of likelihood, idopathic, immune-mediated and neoplastic causes of feline uveitis are univerasal. Patient group Patients of either gender and all ages and breeds are affected by uveitis. Evidence base Despite the fact that feline uveitis is a serious and common disorder, the peer-reviewed literature regarding this disease is somewhat limited. Approximately half the publications are review articles, case reports or case series. The majority of prospective and retrospective research describes epidemiologic surveys of antibodies, antigens and organism DNA in serum and aqueous humor.


title: Monitoring disease transmissibility of 2019 novel coronavirus disease in Zhejiang, China()

text: Owing to the frequent travel connections between Wuhan and Zhejiang, Zhejiang was the third worst-affected province in China with 1,205 cases confirmed before 26 February 2020. The transmissibility of the 2019 novel coronavirus disease was monitored in Zhejiang, accounting for the transmissions from imported cases. Even though Zhejiang was one of the worst-affected provinces, an interruption of disease transmission (i.e. instantaneous reproduction numbers <1) was observed in early/mid-February after a comprehensive set of interventions combating the outbreak.


title: Foal Diarrhea Established and Postulated Causes, Prevention, Diagnostics, and Treatments

text: Diarrhea is one of the most important diseases in young foals and may occur in more than half of foals until weaning age. Several infectious and noninfectious underlying causes have been implicated but scientific evidence of pathogenesis is evolving. It is important to investigate all known potential causes and identify infectious agents to avoid outbreaks, evaluate the level of systemic compromise, and establish adequate therapy. It is crucial to differentiate foals that can be managed in field conditions from those that should be sent to a referral center. This article reviews these aspects and recent developments in the diagnostic and therapeutic approaches.


Warped Speed: How COVID-19 Transfected and Transformed Medical Journals


title: Personalized Predictive Models for Symptomatic COVID-19 Patients Using Basic Preconditions: Hospitalizations, Mortality, and the Need for an ICU or Ventilator

text: BACKGROUND: The rapid global spread of the virus SARS-CoV-2 has provoked a spike in demand for hospital care. Hospital systems across the world have been over-extended, including in Northern Italy, Ecuador, and New York City, and many other systems face similar challenges. As a result, decisions on how to best allocate very limited medical resources have come to the forefront. Specifically, under consideration are decisions on who to test, who to admit into hospitals, who to treat in an Intensive Care Unit (ICU), and who to support with a ventilator. Given today’s ability to gather, share, analyze and process data, personalized predictive models based on demographics and information regarding prior conditions can be used to (1) help decision-makers allocate limited resources, when needed, (2) advise individuals how to better protect themselves given their risk profile, (3) differentiate social distancing guidelines based on risk, and (4) prioritize vaccinations once a vaccine becomes available. OBJECTIVE: To develop personalized models that predict the following events: (1) hospitalization, (2) mortality, (3) need for ICU, and (4) need for a ventilator. To predict hospitalization, it is assumed that one has access to a patient’s basic preconditions, which can be easily gathered without the need to be at a hospital. For the remaining models, different versions developed include different sets of a patient’s features, with some including information on how the disease is progressing (e.g., diagnosis of pneumonia). MATERIALS AND METHODS: Data from a publicly available repository, updated daily, containing information from approximately 91,000 patients in Mexico were used. The data for each patient include demographics, prior medical conditions, SARS-CoV-2 test results, hospitalization, mortality and whether a patient has developed pneumonia or not. Several classification methods were applied, including robust versions of logistic regression, and support vector machines, as well as random forests and gradient boosted decision trees. RESULTS: Interpretable methods (logistic regression and support vector machines) perform just as well as more complex models in terms of accuracy and detection rates, with the additional benefit of elucidating variables on which the predictions are based. Classification accuracies reached 61%, 76%, 83%, and 84% for predicting hospitalization, mortality, need for ICU and need for a ventilator, respectively. The analysis reveals the most important preconditions for making the predictions. For the four models derived, these are: (1) for hospitalization: age, gender, chronic renal insufficiency, diabetes, immunosuppression; (2) for mortality: age, SARS-CoV-2 test status, immunosuppression and pregnancy; (3) for ICU need: development of pneumonia (if available), cardiovascular disease, asthma, and SARS-CoV-2 test status; and (4) for ventilator need: ICU and pneumonia (if available), age, gender, cardiovascular disease, obesity, pregnancy, and SARS-CoV-2 test result.


title: Viroporins and inflammasomes: A key to understand virus-induced inflammation

text: Abstract Viroporins are virus encoded proteins that alter membrane permeability and can trigger subsequent cellular signals. Oligomerization of viroporin subunits results in formation of a hydrophilic pore which facilitates ion transport across host cell membranes. These viral channel proteins may be involved in different stages of the virus infection cycle. Inflammasomes are large multimolecular complexes best recognized for their ability to control activation of caspase-1, which in turn regulates the maturation of interleukin-1 β (IL-1β) and interleukin 18 (IL-18). IL-1β was originally identified as a pro-inflammatory cytokine able to induce both local and systemic inflammation and a febrile reaction in response to infection or injury. Excessive production of IL-1β is associated with autoimmune and inflammatory diseases. Microbial derivatives, bacterial pore-forming toxins, extracellular ATP and other pathogen-associated molecular patterns trigger activation of NLRP3 inflammasomes. Recent studies have reported that viroporin activity is capable of inducing inflammasome activity and production of IL-1β, where NLRP3 is shown to be regulated by fluxes of K+, H+ and Ca2+ in addition to reactive oxygen species, autophagy and endoplasmic reticulum stress. The aim of this review is to present an overview of the key findings on viroporin activity with special emphasis on their role in virus immunity and as possible activators of inflammasomes.


title: First case of a natural infection in a domestic cat (Felis catus) with the canid heart worm Angiostrongylus vasorum

text: Abstract Cardiopulmonary nematodes in cats include different parasite species affecting feline lungs and the heart, with the metastrongyloid Aelurostrongylus abstrusus being the most frequent feline lungworm worldwide. The present case report describes an 11-month-old male neutered European short hair cat which presented with generalised subcutaneous oedema and pleural and peritoneal effusions. According to clinical examination, abdominal imaging and laboratory analyses, a tentative diagnosis of severe glomerulopathy with massive proteinuria was made. Due to worsening of the clinical signs despite therapeutic interventions and a poor prognosis, the cat was euthanised. Necropsy and histological examinations revealed severe bilateral collagenofibrotic glomerulopathy, generalised oedema and a focal verminous pneumonia with thrombosis in arterial lung vessels containing nematode cross sections. A serum sample was tested for the presence of antibodies against the cat lungworm A. abstrusus, resulting negative. Genetic analyses confirmed the presence of nematode DNA; after exclusion of common lung and heart parasites occurring in cats, DNA of the canid heart worm nematode Angiostrongylus vasorum was identified. This is the first description of a naturally occurring infection with A. vasorum in a cat. Previous experimental studies demonstrated the development of adult male and female A. vasorum worms containing eggs in cats, but no larval excretion in the faeces. Although cats did not become patent, A. vasorum infections were clinically relevant. As A. abstrusus and A. vasorum are both gastropod transmitted nematodes, they may share the same intermediate hosts within overlapping areas. In addition, especially chronic A. abstrusus infected cats become non-patent and do not excrete L1. Considering that patent A. vasorum infections are widespread in the dog and fox population in Switzerland (and several other countries) but are apparently not patent in cats, we cannot exclude that infections with A. vasorum may occur more frequently than expected.


Aerosol generation from high speed ophthalmic instrumentation and the risk of contamination from SARS COVID19


title: Heart and Brain: Complex Relationships for Left Ventricular Dysfunction

text: PURPOSE OF REVIEW: This review summarizes the evidence for the established vascular/hypoperfusion model and explores the new hypothesis that configures the heart/brain axis as an organ system where similar pathogenic mechanisms exploit physiological and pathological changes. RECENT FINDINGS: Although associated by common risk factors, similar epidemiological stratification and common triggers (including inflammation, oxidative stress, and hypoxia), heart failure and Alzheimer’s disease have been, for long time, viewed as pathogenically separate illnesses. The silos began to be broken down with the awareness that vascular dysfunction, and loss of cardiac perfusion pump power, trigger biochemical changes, contributing to the typical hallmark of Alzheimer’s disease (AD)—the accumulation of Aβ plaques and hyperphosphorylated Tau tangles. Compromised blood flow to the brain becomes the paradigm for the “heart-to-head” connection. Compelling evidence of common genetic variants, biochemical characteristics, and the accumulation of Aβ outside the brain suggests a common pathogenesis for heart failure (HF) and AD. These new findings represent just the beginning of the understanding the complex connection between AD and HF requiring further studies and interdisciplinary approaches. SUMMARY: Altogether, the current evidence briefly summarized in this review, highlight a closer and complex relationship between heart failure and Alzheimer’s that goes beyond the vascular/perfusion hypothesis. Genetic and biochemical evidence begin to suggest common pathogenic mechanisms between the two diseases involving a systemic defect in the folding of protein or a seeding at distance of the misfolded proteins from one organ to the other.


title: siRNA for Influenza Therapy

text: Influenza virus is one of the most prevalent and ancient infections in humans. About a fifth of world’s population is infected by influenza virus annually, leading to high morbidity and mortality, particularly in infants, the elderly and the immunocompromised. In the US alone, influenza outbreaks lead to roughly 30,000 deaths each year. Current vaccines and anti-influenza drugs are of limited use due to high mutation rate of the virus and side effects. In recent years, RNA interference, triggered by synthetic short interfering RNA (siRNA), has rapidly evolved as a potent antiviral regimen. Properly designed siRNAs have been shown to function as potent inhibitors of influenza virus replication. The siRNAs outperform traditional small molecule antivirals in a number of areas, such as ease of design, modest cost, and fast turnaround. Although specificity and tissue delivery remain major bottlenecks in the clinical applications of RNAi in general, intranasal application of siRNA against respiratory viruses including, but not limited to influenza virus, has experienced significant success and optimism, which is reviewed here.


title: Cleavage of a Neuroinvasive Human Respiratory Virus Spike Glycoprotein by Proprotein Convertases Modulates Neurovirulence and Virus Spread within the Central Nervous System

text: Human coronaviruses (HCoV) are respiratory pathogens that may be associated with the development of neurological diseases, in view of their neuroinvasive and neurotropic properties. The viral spike (S) glycoprotein is a major virulence factor for several coronavirus species, including the OC43 strain of HCoV (HCoV-OC43). In an attempt to study the role of this protein in virus spread within the central nervous system (CNS) and neurovirulence, as well as to identify amino acid residues important for such functions, we compared the sequence of the S gene found in the laboratory reference strain HCoV-OC43 ATCC VR-759 to S sequences of viruses detected in clinical isolates from the human respiratory tract. We identified one predominant mutation at amino acid 758 (from RRSR↓ G (758) to RRSR↓R (758)), which introduces a putative furin-like cleavage (↓) site. Using a molecular cDNA infectious clone to generate a corresponding recombinant virus, we show for the first time that such point mutation in the HCoV-OC43 S glycoprotein creates a functional cleavage site between the S1 and S2 portions of the S protein. While the corresponding recombinant virus retained its neuroinvasive properties, this mutation led to decreased neurovirulence while potentially modifying the mode of virus spread, likely leading to a limited dissemination within the CNS. Taken together, these results are consistent with the adaptation of HCoV-OC43 to the CNS environment, resulting from the selection of quasi-species harboring mutations that lead to amino acid changes in viral genes, like the S gene in HCoV-OC43, which may contribute to a more efficient establishment of a less pathogenic but persistent CNS infection. This adaptative mechanism could potentially be associated with human encephalitis or other neurological degenerative pathologies.


title: Analysis of User Satisfaction with Online Education Platforms in China during the COVID-19 Pandemic

text: The outbreak of Corona Virus Disease 2019 (COVID-19) in various countries at the end of last year has transferred traditional face-to-face teaching to online education platforms, which directly affects the quality of education Taking user satisfaction on online education platforms in China as the research object, this paper uses a questionnaire survey and web crawler to collect experience data of online and offline users, constructs a customer satisfaction index system by analyzing emotion and the existing literature for quantitative analysis, and builds aback propagation (BP) neural network model to forecast user satisfaction The conclusion shows that users' personal factors have no direct influence on user satisfaction, while platform availability has the greatest influence on user satisfaction Finally, suggestions on improving the online education platform are given to escalate the level of online education during the COVID-19 pandemic, so as to promote the reform of information-based education


title: Murine immune responses to a Plasmodium vivax-derived chimeric recombinant protein expressed in Brassica napus

text: BACKGROUND: To develop a plant-based vaccine against Plasmodium vivax, two P. vivax candidate proteins were chosen. First, the merozoite surface protein-1 (MSP-1), a major asexual blood stage antigen that is currently considered a strong vaccine candidate. Second, the circumsporozoite protein (CSP), a component of sporozoites that contains a B-cell epitope. METHODS: A synthetic chimeric recombinant 516 bp gene encoding containing PvMSP-1, a Pro-Gly linker motif, and PvCSP was synthesized; the gene, named MLC, encoded a total of 172 amino acids. The recombinant gene was modified with regard to codon usage to optimize gene expression in Brassica napus. The Ti plasmid inducible gene transfer system was used for MLC chimeric recombinant gene expression in B. napus. Gene expression was confirmed by polymerase chain reaction (PCR), beta-glucuronidase reporter gene (GUS) assay, and Western blot. RESULTS: The MLC chimeric recombinant protein expressed in B. napus had a molecular weight of approximately 25 kDa. It exhibited a clinical sensitivity of 84.21% (n = 38) and a clinical specificity of 100% (n = 24) as assessed by enzyme-linked immunosorbent assay (ELISA). Oral immunization of BALB/c mice with MLC chimeric recombinant protein successfully induced antigen-specific IgG1 production. Additionally, the Th1-related cytokines IL-12 (p40), TNF, and IFN-γ were significantly increased in the spleens of the BALB/c mice. CONCLUSIONS: The chimeric MLC recombinant protein produced in B. napus has potential as both as an antigen for diagnosis and as a valuable vaccine candidate for oral immunization against vivax malaria.


title: The protective and pathogenic roles of CXCL17 in human health and disease: Potential in respiratory medicine

text: Abstract C-X-C motif chemokine 17 (CXCL-17) is a novel chemokine that plays a functional role maintaining homeostasis at distinct mucosal barriers, including regulation of myeloid-cell recruitment, angiogenesis, and control of microorganisms. Particularly, CXCL17 is produced along the epithelium of the airways both at steady state and under inflammatory conditions. While increased CXCL17 expression is associated with disease progression in pulmonary fibrosis, asthma, and lung/hepatic cancer, it is thought to play a protective role in pancreatic cancer, autoimmune encephalomyelitis and viral infections. Thus, there is emerging evidence pointing to both a harmful and protective role for CXCL17 in human health and disease, with therapeutic potential for translational applications. In this review, we provide an overview of the discovery, characteristics and functions of CXCL17 emphasizing its clinical potential in respiratory disorders.


title: Psychological, Political, and Situational Factors Combine to Boost COVID-19 Conspiracy Theory Beliefs

text: Conspiracy theories (CTs) are not solely the domain of extremists and paranoids. They cut across demographic and political differences (Uscinski and Parent, 2014) and can have negative social/political consequences. For example, Imhoff and Lamberty (2020) find that belief that the seriousness of COVID-19 is being exaggerated is negatively correlated with self-reported preventative behaviours such as hand washing and social distancing, and belief that the virus was intentionally created by humans is positively correlated with self-reported hoarding of food, sanitary products, and gasoline/oil, as well as stocking up on weapons.


title: Association between a Novel Human Coronavirus and Kawasaki Disease

text: Kawasaki disease is a systemic vasculitis of childhood; its etiology is unknown. We identified evidence of a novel human coronavirus, designated “New Haven coronavirus” (HCoVNH), in respiratory secretions from a 6-month-old infant with classic Kawasaki disease. To further investigate the possible association between HCoV-NH infection and Kawasaki disease, we conducted a case-control study. Specimens of respiratory secretions from 8 (72.7%) of 11 children with Kawasaki disease and from 1 (4.5%) of 22 control subjects (children without Kawasaki disease matched by age and the time the specimens were obtained) tested positive for HCoVNH by reverse-transcriptase polymerase chain reaction (Mantel-Haenszel matched odds ratio, 16.0 [95% confidence interval, 3.4–74.4]; P = .0015). These data suggest that HCoV-NH infection is associated with Kawasaki disease.


title: Photoantimicrobials—are we afraid of the light?

text: Although conventional antimicrobial drugs have been viewed as miraculous cure-alls for the past 80 years, increasing antimicrobial drug resistance requires a major and rapid intervention. However, the development of novel but still conventional systemic antimicrobial agents, having only a single mode or site of action, will not alleviate the situation because it is probably only a matter of time until any such agents will also become ineffective. To continue to produce new agents based on this notion is unacceptable, and there is an increasing need for alternative approaches to the problem. By contrast, light-activated molecules called photoantimicrobials act locally via the in-situ production of highly reactive oxygen species, which simultaneously attack various biomolecular sites in the pathogenic target and therefore offer both multiple and variable sites of action. This non-specificity at the target circumvents conventional mechanisms of resistance and inhibits the development of resistance to the agents themselves. Photoantimicrobial therapy is safe and easy to implement and, unlike conventional agents, the activity spectrum of photoantimicrobials covers bacteria, fungi, viruses, and protozoa. However, clinical trials of these new, truly broad-spectrum, and minimally toxic agents have been few, and the funding for research and development is almost non-existent. Photoantimicrobials constitute one of the few ways forward through the morass of drug-resistant infectious disease and should be fully explored. In this Personal View, we raise awareness of the novel photoantimicrobial technologies that offer a viable alternative to conventional drugs in many relevant application fields, and could thus slow the pace of resistance development.


title: Viruses of Respiratory Tract: an Observational Retrospective Study on Hospitalized Patients in Rome, Italy

text: Respiratory tract infections account for high morbidity and mortality around the world. Fragile patients are at high risk of developing complications such as pneumonia and may die from it. Limited information is available on the extent of the circulation of respiratory viruses in the hospital setting. Most knowledge relates to influenza viruses (FLU) but several other viruses produce flu-like illness. The study was conducted at the University Hospital Policlinico Tor Vergata, Rome, Italy. Clinical and laboratory data from hospitalized patients with respiratory tract infections during the period October 2016–March 2019 were analysed. The retrospective analysis included 17 viral agents detected by FilmArray test and clinical data from medical records and hospital discharge sheets. Models were adjusted for relevant confounders such as clinical severity and risk of death, socio-demographic characteristics and surgical procedures. From a total of 539 specimens analysed, 180 (33.39%) were positive for one or more respiratory viruses. Among them, 83 (46.1 %) were positive for influenza viruses (FLU), 36 (20%) rhino/enteroviruses (RHV/EV), 17 (9.44%) human coronaviruses (HCOV-229E, -HKU1, -NL63, and -OC43), 17 (9.44%) respiratory syncytial virus, 15 (8.33%) human metapneumovirus (HMPV), 8 (4.44%) parainfluenza viruses (PIV) and 4 (2.22%) adenoviruses (ADV). The distribution of viral agents varied across age groups and month of detection. The positive specimens were from 168 patients [102 M, 66 F; median age (range): 64 years (19−93)]. Overall, 40% of them had a high-grade clinical severity and a 27% risk of death; 27 patients died and 22 of them (81.5%) had received a clinical diagnosis of pneumonia. Respiratory viral infections may have a severe course and a poor prognosis in hospitalized patients, due to underlying comorbidities. Monitoring the circulation of respiratory viruses in hospital settings is important to improve diagnosis, prevention and treatment.


title: Arrhythmic profile and 24-hour QT interval variability in COVID-19 patients treated with hydroxychloroquine and azithromycin

text: BACKGROUND: Hydroxychloroquine and azithromycin combination therapy is often prescribed for coronavirus disease 2019 (COVID-19). Electrocardiographic (ECG) monitoring is warranted because both medications cause corrected QT-interval (QTc) prolongation. Whether QTc duration significantly varies during the day, potentially requiring multiple ECGs, remains to be established. METHODS: We performed 12‑lead ECGs and 12‑lead 24-h Holter ECG monitoring in all patients aged <80 years admitted to our medical unit for COVID-19, in oral therapy with hydroxychloroquine (200 mg, twice daily) and azithromycin (500 mg, once daily) for at least 3 days. A group of healthy individuals matched for age and sex served as control. RESULTS: Out of 126 patients, 22 (median age 64, 82% men) met the inclusion criteria. ECG after therapy showed longer QTc-interval than before therapy (450 vs 426 ms, p = .02). Four patients had a QTc ≥ 480 ms: they showed higher values of aspartate aminotransferase (52 vs 30 U/L, p = .03) and alanine aminotransferase (108 vs 33 U/L, p < .01) compared with those with QTc < 480 ms. At 24-h Holter ECG monitoring, 1 COVID-19 patient and no control had ≥1 run of non-sustained ventricular tachycardia (p = .4). No patients showed “R on T" premature ventricular beats. Analysis of 24-h QTc dynamics revealed that COVID-19 patients had higher QTc values than controls, with no significant hourly variability. CONCLUSION: Therapy with hydroxychloroquine and azithromycin prolongs QTc interval in patients with COVID-19, particularly in those with high levels of transaminases. Because QTc duration remains stable during the 24 h, multiple daily ECG are not recommendable.


title: Diagnosis of Viral Respiratory Infections in the 1980s

text: The introduction of immunologic techniques for rapid viral diagnosis and the availability of high quality commercial reagents have resulted in significant advances in the laboratory diagnosis of viral respiratory infections. Laboratories just beginning in the area of diagnostic virology are advised to direct their efforts at viral isolation using cell types such as human embryonic kidney; immunofluorescence and other techniques of rapid viral diagnosis are recommended when the laboratory is prepared to expand.


title: Identification of a potent benzoxaborole drug candidate for treating cryptosporidiosis

text: Cryptosporidiosis is a leading cause of life-threatening diarrhea in young children and causes chronic diarrhea in AIDS patients, but the only approved treatment is ineffective in malnourished children and immunocompromised people. We here use a drug repositioning strategy and identify a promising anticryptosporidial drug candidate. Screening a library of benzoxaboroles comprised of analogs to four antiprotozoal chemical scaffolds under pre-clinical development for neglected tropical diseases for Cryptosporidium growth inhibitors identifies the 6-carboxamide benzoxaborole AN7973. AN7973 blocks intracellular parasite development, appears to be parasiticidal, and potently inhibits the two Cryptosporidium species most relevant to human health, C. parvum and C. hominis. It is efficacious in murine models of both acute and established infection, and in a neonatal dairy calf model of cryptosporidiosis. AN7973 also possesses favorable safety, stability, and PK parameters, and therefore, is an exciting drug candidate for treating cryptosporidiosis.