title: The use of digital technologies by small and medium enterprises during COVID-19: Implications for theory and practice

text: Scholars have highlighted the role of Digital Technologies (DT) in enhancing productivity and performance in Small and Medium Enterprises (SMEs). However, there is limited evidence on the use of DT for dealing with the consequences of extreme events, such as COVID-19. We discuss this gap by (i) outlining potential research avenues and (ii) reflecting on the managerial implications of using DT within SMEs to deal with the repercussions of COVID-19 and securing business continuity.


The evolution of pharmacists' roles in disasters, from logistics to assessing and prescribing.


docid: isziopnl

title: Influenza A virus H5N1 entry into host cells is through clathrin-dependent endocytosis

text: Influenza A virus H5N1 presents a major threat to human health. The entry of influenza virus into host cells is believed to be mediated by hemagglutinin (HA), a virus surface glycoprotein that can bind terminal sialic acid residues on host cell glycoproteins and glycolipids. In this study, we elucidated the pathways through which H5N1 enters human lung carcinoma cell line A549. We first proved that H5N1 can enter A549 cells via endocytosis, as lysosomotropic agents, such as bafilomycin A1 and chloroquine, can rescue H5N1-induced A549 cell death. By using specific inhibitors, and siRNAs that target the clathrin pathway, we further found that H5N1 could enter A549 cells via clathrin-mediated endocytosis, while inhibitors targeting caveolae-mediated endocytosis could not inhibit H5N1 cell entry. These findings expand our understanding of H5N1 pathogenesis and provide new information for anti-viral drug research.


docid: kaigrqmd

title: Controversy over antibacterial silver: implications for environmental and sustainability assessments

text: Abstract The potential risks and benefits of using silver, especially nanosilver, as an antibacterial agent in consumer and healthcare products are under debate globally. Using content analysis of texts from newspaper and TV, government agencies, municipalities, government and parliament, non-governmental organizations, and companies, we analyze the argumentation in the Swedish public controversy over antibacterial silver and relate the findings to environmental and sustainability assessments. We conclude that silver is regarded as either beneficial or harmful in relation to four main values: the environment, health, sewage treatment, and product effectiveness. Various arguments are used to support positive and negative evaluations of silver, revealing several contradictory reasons for considering silver beneficial or harmful. Current environmental and sustainability assessments (i.e. substance flow analysis, risk analysis, multi-criteria analysis, and lifecycle assessment) cover many of the concerns raised in the public controversy over antibacterial silver and can therefore inform the debate regarding its toxicity, emissions, and environmental impact. However, not all concerns raised in the public controversy are covered by current environmental and sustainability assessments, most notably, concerns over public health and bacterial resistance issues are not paid full attention. For future environmental and sustainability assessments to make an even more significant societal contribution and to inform consumers and decision-makers about concerns articulated in the public debate, a wider range of issues concerning antibacterial silver needs to be considered through a unified framework.


title: Microglia have a protective role in viral encephalitis-induced seizure development and hippocampal damage

text: Abstract In the central nervous system (CNS), innate immune surveillance is mainly coordinated by microglia. These CNS resident myeloid cells are assumed to help orchestrate the immune response against infections of the brain. However, their specific role in this process and their interactions with CNS infiltrating immune cells, such as blood-borne monocytes and T cells are only incompletely understood. The recent development of PLX5622, a specific inhibitor of colony-stimulating factor 1 receptor that depletes microglia, allows studying the role of microglia in conditions of brain injury such as viral encephalitis, the most common form of brain infection. Here we used this inhibitor in a model of viral infection-induced epilepsy, in which C57BL/6 mice are infected by a picornavirus (Theiler’s murine encephalomyelitis virus) and display seizures and hippocampal damage. Our results show that microglia are required early after infection to limit virus distribution and persistence, most likely by modulating T cell activation. Microglia depletion accelerated the occurrence of seizures, exacerbated hippocampal damage, and led to neurodegeneration in the spinal cord, which is normally not observed in this mouse strain. This study enhances our understanding of the role of microglia in viral encephalitis and adds to the concept of microglia-T cell crosstalk.


Internet Search Limitations and Pandemic Influenza, Singapore


title: Pushing the Bacterial Envelope: Strategies for Re-Engineering Bacterial Surfaces with Heterologous Proteins and Sugars

text: Over the past three decades, a powerful array of techniques has been developed for expressing heterologous proteins and saccharides on the surface of bacteria. Surface-engineered bacteria, in turn, have proven useful in a variety of settings, including high-throughput screening, biofuel production, and vaccinology. In this chapter, we provide a comprehensive review of methods for displaying polypeptides and sugars on the bacterial cell surface, and discuss the many innovative applications these methods have found to date. While already an important biotechnological tool, we believe bacterial surface display may be further improved through integration with emerging methodology in other fields, such as protein engineering and synthetic chemistry. Ultimately, we envision bacterial display becoming a multidisciplinary platform with the potential to transform basic and applied research in bacteriology, biotechnology, and biomedicine.


docid: bjyzrmsb

title: A Comprehensive Review of Manifestations of Novel Coronaviruses in the Context of Deadly COVID-19 Global Pandemic

text: Since December 2019, the global pandemic caused by the highly infectious novel coronavirus 2019-nCoV (COVID-19) has been rapidly spreading. As of April 2020, the outbreak has spread to over 210 countries, with over 2,400,000 confirmed cases and over 170,000 deaths [1]. COVID-19 causes a severe pneumonia characterized by fever, cough, and shortness of breath. Similar coronavirus outbreaks have occurred in the past causing severe pneumonia like COVID-19, most recently, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). However, over time, SARS-CoV and MERS-CoV were shown to cause extra-pulmonary signs and symptoms including hepatitis, acute renal failure, encephalitis, myositis, and gastroenteritis. Similarly, sporadic reports of COVID-19 related extrapulmonary manifestations emerge. Unfortunately, there is no comprehensive summary of the multi-organ manifestations of COVID-19, making it difficult for clinicians to quickly educate themselves about this highly contagious and deadly pathogen. What's more, is that SARS-CoV and MERS-CoV are the closest humanity has come to combating something similar to COVID-19, however, there exists no comparison between the manifestations of any of these novel coronaviruses. In this review, we summarize the current knowledge of the manifestations of the novel coronaviruses SARS-CoV, MERS-CoV, and COVID-19, with a particular focus on the latter, and highlight their differences and similarities.


title: Disease Prevention: An Opportunity to Expand Edible Plant-Based Vaccines?

text: The lethality of infectious diseases has decreased due to the implementation of crucial sanitary procedures such as vaccination. However, the resurgence of pathogenic diseases in different parts of the world has revealed the importance of identifying novel, rapid, and concrete solutions for control and prevention. Edible vaccines pose an interesting alternative that could overcome some of the constraints of traditional vaccines. The term “edible vaccine” refers to the use of edible parts of a plant that has been genetically modified to produce specific components of a particular pathogen to generate protection against a disease. The aim of this review is to present and critically examine “edible vaccines” as an option for global immunization against pathogenic diseases and their outbreaks and to discuss the necessary steps for their production and control and the list of plants that may already be used as edible vaccines. Additionally, this review discusses the required standards and ethical regulations as well as the advantages and disadvantages associated with this powerful biotechnology tool.


Editorial: New Advances in RNA Targeting


title: Contributions of international cooperation projects to the HIV/AIDS response in China

text: Background For 20 years, China has participated in 267 international cooperation projects against the HIV/AIDS epidemic and received ∼526 million USD from over 40 international organizations. These projects have played an important role by complementing national efforts in the fight against HIV/AIDS in China. Methods The diverse characteristics of these projects followed three phases over 20 years. Initially, stand-alone projects provided technical support in surveillance, training or advocacy for public awareness. As the epidemic spread across China, projects became a part of the comprehensive and integrated national response. Currently, international best practices encourage the inclusion of civil society and non-governmental organizations in an expanded response to the epidemic. Results Funding from international projects has accounted for one-third of the resources provided for the HIV/AIDS response in China. Beyond this strong financial support, these programmes have introduced best practices, accelerated the introduction of AIDS policies, strengthened capacity, improved the development of grassroots social organizations and established a platform for communication and experience sharing with the international community. However, there are still challenges ahead, including integrating existing resources and exploring new programme models. The National Centre for AIDS/STD Control and Prevention (NCAIDS) in China is consolidating all international projects into national HIV prevention, treatment and care activities. Conclusion International cooperation projects have been an invaluable component of China’s response to HIV/AIDS, and China has now been able to take this information and share its experiences with other countries with the help of these same international programmes.


title: Cryo X-ray nano-tomography of vaccinia virus infected cells

text: Abstract We have performed full-field cryo X-ray microscopy in the water window photon energy range on vaccinia virus (VACV) infected cells to produce tomographic reconstructions. PtK2 cells were infected with a GFP-expressing VACV strain and frozen by plunge fast freezing. The infected cells were selected by light fluorescence microscopy of the GFP marker and subsequently imaged in the X-ray microscope under cryogenic conditions. Tomographic tilt series of X-ray images were used to yield three-dimensional reconstructions showing different cell organelles (nuclei, mitochondria, filaments), together with other structures derived from the virus infection. Among them, it was possible to detect viral factories and two types of viral particles related to different maturation steps of VACV (immature and mature particles), which were compared to images obtained by standard electron microscopy of the same type of cells. In addition, the effect of radiation damage during X-ray tomographic acquisition was analyzed. Thin sections studied by electron microscopy revealed that the morphological features of the cells do not present noticeable changes after irradiation. Our findings show that cryo X-ray nano-tomography is a powerful tool for collecting three-dimensional structural information from frozen, unfixed, unstained whole cells with sufficient resolution to detect different virus particles exhibiting distinct maturation levels.


title: Transfusion Risks and Transfusion-related Pro-inflammatory Responses

text: Despite improvements in blood screening and administration techniques, serious adverse events related to transfusion continue to occur, albeit at a much lower incidence. In addition to the development and implementation of new screening and blood purification/modification techniques and implementation of an optimal blood management program, the incidence and consequences of transfusion reactions can be reduced by a basic understanding of transfusion-related complications. Although acute hemolytic transfusion reactions, transfusion-associated anaphylaxis and sepsis, and transfusion-associated acute lung injury occur infrequently, diligence in administration of blood and monitoring for development of respective signs/symptoms can minimize the severity of these potentially life-threatening complications. In addition, emerging blood-banking techniques such as psoralen-UV inactivation of pathogens and use of patient identification systems may attenuate the incidence of adverse events related to transfusion. With respect to optimizing blood management by means of an effective blood management program involving pharmacologic and nonpharmacologic strategies, the ability to reduce use of blood products and to decrease operative time or re-exploration rates has important implications for disease prevention, blood inventory and costs, and overall health care costs.


title: Efficacy of hydroxychloroquine for post-exposure prophylaxis to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among adults exposed to coronavirus disease (COVID-19): a structured summary of a study protocol for a randomised controlled trial

text: OBJECTIVES: Primary Objective • To test the efficacy of Hydroxychloroquine (HCQ) (400 mg orally daily for 3 days then 200 mg orally daily for an additional 11 days, to complete 14 days) to prevent incident SARS-CoV-2 infection, compared to ascorbic acid among contacts of persons with SARS-CoV-2 infection Secondary objectives • To determine the safety and tolerability of HCQ as SARS-CoV-2 Post-exposure Prophylaxis (PEP) in adults • To test the efficacy of HCQ (400 mg orally daily for 3 days then 200 mg orally daily for an additional 11 days, to complete 14 days) to prevent incident SARS-CoV-2 infection 2 weeks after completing therapy, compared to ascorbic acid among contacts of persons with SARS-CoV-2 infection • To test the efficacy of HCQ to shorten the duration of SARS-CoV-2 shedding among those with SARS-CoV-2 infection in the HCQ PEP group • To test the efficacy of HCQ to prevent incident COVID-19 TRIAL DESIGN: This is a randomized, multi-center, placebo-equivalent (ascorbic acid) controlled, blinded study of HCQ PEP for the prevention of SARS-CoV-2 infection in adults exposed to the virus. PARTICIPANTS: This study will enroll up to 2000 asymptomatic adults 18 to 80 years of age (inclusive) at baseline who are close contacts of persons with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 or clinically suspected COVID-19 and a pending SARS-CoV-2 PCR test. This multisite trial will be conducted at seven sites in Seattle (UW), Los Angeles (UCLA), New Orleans (Tulane), Baltimore (UMB), New York City (NYU), Syracuse (SUNY-Upstate), and Boston (BMC). Inclusion criteria 1. Men or women 18 to 80 years of age inclusive, at the time of signing the informed consent. 2. Willing and able to provide informed consent. 3. Had a close contact of a person (index) with known PCR-confirmed SARS-CoV-2 infection or index who is currently being assessed for COVID-19. a. Household contact (i.e., residing with the index case in the 14 days prior to index diagnosis or prolonged exposure within a residence/vehicle/enclosed space without maintaining social distance). b. Medical staff, first responders, or other care persons who cared for the index case without personal protection (mask and gloves): 4. Less than 4 days since last exposure (close contact with a person with SARS-CoV-2 infection) to the index case; 5. Access to device and internet for Telehealth visits; 6. Not planning to take HCQ in addition to the study medication. Exclusion criteria 1. Known hypersensitivity to HCQ or other 4-aminoquinoline compounds. 2. Currently hospitalized. 3. Symptomatic with subjective fever, cough, or shortness of breath. 4. Current medications exclude concomitant use of HCQ. 5. Concomitant use of other anti-malarial treatment or chemoprophylaxis, including chloroquine, mefloquine, artemether, or lumefantrine. 6. History of retinopathy of any etiology. 7. Psoriasis. 8. Porphyria. 9. Known bone marrow disorders with significant neutropenia (polymorphonuclear leukocytes <1500) or thrombocytopenia (<100 K). 10. Concomitant use of digoxin, cyclosporin, cimetidine, amiodarone, or tamoxifen. 11. Known moderate or severe liver disease. 12. Known long QT syndrome. 13. Severe renal impairment. 14. Use of any investigational or non-registered drug or vaccine within 30 days preceding the first dose of the study drugs or planned use during the study period. INTERVENTION AND COMPARATOR: Households will be randomized 1:1 (at the level of household), with close contact participants receiving one of the following therapies: •HCQ 400 mg orally daily for 3 days then 200 mg orally daily for an additional 11 days •Placebo-like control (ascorbic acid) 500 mg orally daily for 3 days then 250 mg orally daily for 11 days MAIN OUTCOMES: The primary outcome of the study is the incidence of SARS-CoV-2 infection through day 14 among participants who are SARS-CoV-2 negative at baseline by randomization group. RANDOMISATION: Participants will be randomized in a 1:1 ratio to HCQ or ascorbic acid at the level of the household (all eligible participants in 1 household will receive the same intervention). The randomization code and resulting allocation list will be generated and maintained by the Study Statistician. The list will be blocked and stratified by site and contact type (household versus healthcare worker). BLINDING (MASKING): This is a blinded study. HCQ and ascorbic acid will appear similar, and taste will be partially masked as HCQ can be bitter and ascorbic acid will be sour. The participants will be blinded to their randomization group once assigned. Study team members, apart from the Study Pharmacist and the unblinded statistical staff, will be blinded. Laboratory staff are blinded to the group allocation. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The sample size for the study is N=2 000 participants randomized 1:1 to either HCZ (n=1 000) and ascorbic acid (n=1 000). TRIAL STATUS: Protocol version: 1.2 05 April 2020 Recruitment is ongoing, started March 31 and anticipated end date is September 30, 2020. TRIAL REGISTRATION: ClinicalTrials.gov, Protocol Registry Number: NCT04328961 Date of registration: April 1, 2020, retrospectively registered FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


docid: guajptuc

title: Diverse microbial interactions with the basement membrane barrier

text: During primary contact with susceptible hosts, microorganisms face an array of barriers that thwart their invasion process. Passage through the basement membrane (BM), a 50–100-nm-thick crucial barrier underlying epithelia and endothelia, is a prerequisite for successful host invasion. Such passage allows pathogens to reach nerve endings or blood vessels in the stroma and to facilitate spread to internal organs. During evolution, several pathogens have developed different mechanisms to cross this dense matrix of sheet-like proteins. To breach the BM, some microorganisms have developed independent mechanisms, others hijack host cells that are able to transverse the BM (e.g. leukocytes and dendritic cells) and oncogenic microorganisms might even trigger metastatic processes in epithelial cells to penetrate the underlying BM.


docid: hnodrgnp

title: Bringing them together: Plasmid pMV158 rolling circle replication and conjugation under an evolutionary perspective

text: Rolling circle-replicating plasmids constitute a vast family that is particularly abundant in, but not exclusive of, Gram-positive bacteria. These plasmids are constructed as cassettes that harbor genes involved in replication and its control, mobilization, resistance determinants and one or two origins of lagging strand synthesis. Any given plasmid may contain all, some, or just only the replication cassette. We discuss here the family of the promiscuous streptococcal plasmid pMV158, with emphasis on its mobilization functions: the product of the mobM gene, prototype of the MOB(V) relaxase family, and its cognate origin of transfer, oriT. Amongst the subfamily of MOB(V1) plasmids, three groups of oriT sequences, represented by plasmids pMV158, pT181, and p1414 were identified. In the same subfamily, we found four types of single-strand origins, namely ssoA, ssoU, ssoW, and ssoT. We found that plasmids of the rolling-circle Rep_2 family (to which pMV158 belongs) are more frequently found in Lactobacillales than in any other bacterial order, whereas Rep_1 initiators seemed to prefer hosts included in the Bacillales order. In parallel, MOB(V1) relaxases associated with Rep_2 initiators tended to cluster separately from those linked to Rep_1 plasmids. The updated inventory of MOB(V1) plasmids still contains exclusively mobilizable elements, since no genes associated with conjugative transfer (other than the relaxase) were detected. These plasmids proved to have a great plasticity at using a wide variety of conjugative apparatuses. The promiscuous recognition of non-cognate oriT sequences and the role of replication origins for lagging-strand origin in the host range of these plasmids are also discussed.


title: Advances in prevention and therapy of neonatal dairy calf diarrhoea: a systematical review with emphasis on colostrum management and fluid therapy

text: Neonatal calf diarrhoea remains the most common cause of morbidity and mortality in preweaned dairy calves worldwide. This complex disease can be triggered by both infectious and non-infectious causes. The four most important enteropathogens leading to neonatal dairy calf diarrhoea are Escherichia coli, rota- and coronavirus, and Cryptosporidium parvum. Besides treating diarrhoeic neonatal dairy calves, the veterinarian is the most obvious person to advise the dairy farmer on prevention and treatment of this disease. This review deals with prevention and treatment of neonatal dairy calf diarrhoea focusing on the importance of a good colostrum management and a correct fluid therapy.


title: SARS‐unique fold in the Rousettus bat coronavirus HKU9

text: The coronavirus nonstructural protein 3 (nsp3) is a multifunctional protein that comprises multiple structural domains. This protein assists viral polyprotein cleavage, host immune interference, and may play other roles in genome replication or transcription. Here, we report the solution NMR structure of a protein from the “SARS‐unique region” of the bat coronavirus HKU9. The protein contains a frataxin fold or double‐wing motif, which is an α + β fold that is associated with protein/protein interactions, DNA binding, and metal ion binding. High structural similarity to the human severe acute respiratory syndrome (SARS) coronavirus nsp3 is present. A possible functional site that is conserved among some betacoronaviruses has been identified using bioinformatics and biochemical analyses. This structure provides strong experimental support for the recent proposal advanced by us and others that the “SARS‐unique” region is not unique to the human SARS virus, but is conserved among several different phylogenetic groups of coronaviruses and provides essential functions.


title: CPR News

text: The International Institute for Conflict Prevention and Resolution in March launched a resource page on its website for conflict resolution in commercial matters when the coronavirus pandemic requires closings and social distancing.


title: Posttraumatic Stress Disorder in Primary Care: A Study of General Practices in England

text: Posttraumatic Stress Disorder (PTSD) may be a common issue in primary care in the UK, but there have been no studies of all-cause PTSD in general samples of attenders in this country. The current paper thus explores the extent and distribution of probable PTSD among patients attending general practices in England. Cross-sectional survey data from adult patients (n = 1058) attending 11 general practices in southwest England were analysed. Patients were recruited from waiting rooms and completed anonymous questionnaires, including measures of depression, anxiety and risky alcohol use. Current probable PTSD was measured using the 4-item Primary Care PTSD Scale (PC-PTSD). Results indicated 15.1% of patients that exhibited probable PTSD (PC-PTSD ≥ 3), with higher levels observed in practices from deprived areas. There were 53.8% of patients with probable PTSD that expressed the desire for help with these issues. The analyses suggested that rates were lowest among older adults, and highest among patients who were not in cohabitating relationships or were unemployed. Measures of anxiety and depression were associated with 10-fold and 16-fold increases in risk of probable PTSD, respectively, although there were no discernible associations with risky drinking. Such preliminary findings highlight the need for vigilance for PTSD in routine general practice in the UK, and signal a strong need for additional research and attention in this context.


title: Redeploying plant defences

text: Epidemic diseases are not a new phenomenon, but easy access to transport in the modern world has accelerated their spread. Perhaps some botanical understanding can help slow them down.


title: “Global Health”: Time to Refocus while We still Have Time

text: Two decades of growing resource availability from agencies and foundations in wealthy countries has transformed approaches to health in poorly resourced nations. This progress looks increasingly unstable as climate change, social unrest, and, now, disruptive pandemics present threats not only to health but also to the mechanisms that manage it, and to funding itself. The growth in “global health” schools, technology development laboratories, nongovernmental organizations and multilateral institutions in donor countries has delivered not only successes but also disappointment, and reflect a paradigm that is in many ways contrary to the principles of population-based ownership that they espouse. Although the COVID-19 crisis has underlined the importance of health access and health service capacity, we may have a limited window of opportunity in which to rethink the current model and improve both efficiency and effectiveness. With a dose of humility, we may all benefit from studying our own rhetoric on human-centered design and applying these principles across global health to ensure that our approach is effective, efficient, and defensible.


title: Inquiries to consumer lines manageable, but blitz from COVID‐19 may be coming

text: Operators of the many sources of telephone‐based mental health crisis support across the nation wonder whether a fairly busy March of fielding concerns about the novel coronavirus could transition to an unmanageable April.


title: A descriptive study of acute outbreaks of respiratory disease in Norwegian fattening pig herds

text: BACKGROUND: Respiratory diseases are major health concerns in the pig production sector worldwide, contributing adversely to morbidity and mortality. Over the past years there was a rise in reported incidents of respiratory disease in pigs in Norway, despite population wide freedom from Aujeszky´s disease, porcine reproductive and respiratory syndrome, porcine respiratory corona virus and enzootic pneumonia. The main objective of this study was to investigate acute outbreaks of respiratory disease in conventional Norwegian fattening pig herds. The study included 14 herds. In seven herds with reported outbreaks of acute respiratory disease, data on clinical signs was recorded and samples for laboratory examination were collected. Diagnostic protocols were compared by parallel analysis of clinically healthy pigs from seven non-outbreak herds. RESULTS: The most commonly reported clinical signs were sudden deaths and dyspnea. An average compartment morbidity of 60%, mortality of 4% and case fatality of 9% was recorded in the outbreak herds. Post-mortem examinations revealed acute lesions resembling porcine pleuropneumonia in all 28 pigs investigated from the outbreak herds and in 2 of the 24 (8%) pigs from the non-outbreak herds. Chronic lesions were recorded in another 2 pigs (8%) from the non-outbreak herds. Actinobacillus pleuropneumoniae serovar 8 was isolated from lungs and/or pleura from all tested pigs (n = 28) in the outbreak herds, and from 2 out of 24 pigs (8%) in the non-outbreak herds, one pig with an acute and another pig with a chronic infection. No other significant bacterial findings were made. Seroconversion to A. pleuropneumoniae antibodies was detectable in all outbreak herds analyzed and in six out of seven non-outbreak herds, but the risk ratio for seroconversion of individual pigs was higher (risk ratio 2.3 [1.50- 3.43 95% CI; P < 0.001]) in the outbreak herds. All herds tested positive for porcine circovirus type 2 and negative for influenza A viruses on oral fluid RT-qPCR. CONCLUSION: The main etiological pathogen found during acute outbreaks of respiratory disease was A. pleuropneumoniae serovar 8. All pigs from outbreak herds had typical lesions of acute porcine pleuropneumonia, and only A. pleuropneumoniae serovar 8 was identified. Co-infections were not found to impact disease development.


Developing a New Normal During the Coronavirus Pandemic


title: Effects of Nasal or Pulmonary Delivered Treatments with an Adenovirus Vectored Interferon (mDEF201) on Respiratory and Systemic Infections in Mice Caused by Cowpox and Vaccinia Viruses

text: An adenovirus 5 vector encoding for mouse interferon alpha, subtype 5 (mDEF201) was evaluated for efficacy against lethal cowpox (Brighton strain) and vaccinia (WR strain) virus respiratory and systemic infections in mice. Two routes of mDEF201 administration were used, nasal sinus (5-µl) and pulmonary (50-µl), to compare differences in efficacy, since the preferred treatment of humans would be in a relatively small volume delivered intranasally. Lower respiratory infections (LRI), upper respiratory infections (URI), and systemic infections were induced by 50-µl intranasal, 10-µl intranasal, and 100-µl intraperitoneal virus challenges, respectively. mDEF201 treatments were given prophylactically either 24 h (short term) or 56d (long-term) prior to virus challenge. Single nasal sinus treatments of 10(6) and 10(7) PFU/mouse of mDEF201 protected all mice from vaccinia-induced LRI mortality (comparable to published studies with pulmonary delivered mDEF201). Systemic vaccinia infections responded significantly better to nasal sinus delivered mDEF201 than to pulmonary treatments. Cowpox LRI infections responded to 10(7) mDEF201 treatments, but a 10(6) dose was only weakly protective. Cowpox URI infections were equally treatable by nasal sinus and pulmonary delivered mDEF201 at 10(7) PFU/mouse. Dose-responsive prophylaxis with mDEF201, given one time only 56 d prior to initiating a vaccinia virus LRI infection, was 100% protective from 10(5) to 10(7) PFU/mouse. Improvements in lung hemorrhage score and lung weight were evident, as were decreases in liver, lung, and spleen virus titers. Thus, mDEF201 was able to treat different vaccinia and cowpox virus infections using both nasal sinus and pulmonary treatment regimens, supporting its development for humans.


title: Analysis of the association between necrotizing enterocolitis and transfusion of red blood cell in very low birth weight preterm infants

text: PURPOSE: To investigate the association between necrotizing enterocolitis (NEC) and red blood cell transfusions in very low birth weight (VLBW) preterm infants. METHODS: We studied were 180 VLBW preterm infants who were admitted to the neonatal intensive care unit of CHA Gangnam Hospital from January of 2006 to December of 2009. The subjects were divided into 2 groups: an NEC group (greater than stage II on the modified Bell's criteria) and a control group (less than stage II on the modified Bell's critieria). We defined red blood cell transfusion before NEC diagnosis as the frequency of transfusion until NEC diagnosis (mean day at NEC diagnosis, day 18) in the NEC group and the frequency of transfusion until 18 days after birth in the control group. RESULTS: Of the 180 subjects, 18 (10%) belonged to the NEC group, and 14 (78%) of these 18 patients had a history of transfusion before NEC diagnosis. The NEC group received 3.1±2.9 transfusions, and the control group received 1.0±1.1 transfusions before the NEC diagnosis (P=0.005). In a multivariate logistic regression corrected for gestational age, Apgar score at 1 minute, the presence of respiratory distress syndrome, patent ductus arteriosus, premature rupture of membrane, disseminated intravascular coagulopathy and death were confounding factors. The risk of NEC increased 1.63 times (95% confidence interval, 1.145 to 2.305; P=0.007) with transfusion before the NEC diagnosis. CONCLUSION: The risk for NEC increased significantly with increased transfusion frequency before the NEC diagnosis.


title: Modulatory effect of rRNA synthesis and ppUL83 nucleolar compartmentalization on human cytomegalovirus gene expression in vitro

text: The nucleolus is a nuclear domain involved in the biogenesis of ribosomes, as well as in many other important cellular regulatory activities, such as cell cycle control and mRNA processing. Many viruses, including herpesviruses, are known to exploit the nucleolar compartment during their replication cycle. In a previous study, we demonstrated the preferential targeting and accumulation of the human cytomegalovirus (HCMV) UL83 phosphoprotein (pp65) to the nucleolar compartment and, in particular, to the nucleolar matrix of lytically infected fibroblasts; such targeting was already evident at very early times after infection. Here we have investigated the possible effects of rRNA synthesis inhibition upon the development of HCMV lytic infection, by using either actinomycin D or cisplatin at low concentrations, that are known to selectively inhibit RNA polymerase I activity, whilst leaving RNA polymerase II function unaffected. Following the inhibition of rRNA synthesis by either of the agents used, we observed a significant redistribution of nucleolar proteins within the nucleoplasm and a simultaneous depletion of viral pp65 from the nucleolus; this effect was highly evident in both unextracted cells and in nuclear matrices in situ. Of particular interest, even a brief suppression of rRNA synthesis resulted in a very strong inhibition of the progression of HCMV infection, as was concluded from the absence of accumulation of HCMV major immediate‐early proteins within the nucleus of infected cells. These data suggest that a functional relationship might exist between rRNA synthesis, pp65 localization to the nucleolar matrix and the normal development of HCMV lytic infection. J. Cell. Biochem. 108: 415–423, 2009. © 2009 Wiley‐Liss, Inc.


title: Clinical characteristics and outcomes of COVID‐19 patients with gastrointestinal symptoms admitted to Jianghan Fangcang Shelter Hospital in Wuhan, China

text: OBJECTIVE: Coronavirus disease 2019 (COVID‐19) is a health emergency worldwide, and gastrointestinal (GI) symptoms are increasingly reported in COVID‐19 patients. However, sample size was small and the incidence of GI symptoms in patients was variable across studies, and the correlation between these symptoms and clinical outcomes remains incompletely understood. The objective of this study is to compare clinical characteristics and outcomes between patients with and without GI symptoms admitted to Jianghan Fangcang Shelter Hospital in Wuhan. METHODS: All patients admitted to Jianghan Fangcang Shelter Hospital were evaluated. Data on epidemiological and clinical characteristics, laboratory findings, treatment procedures, and clinical outcomes were retrieved from electronic medical records. RESULTS: This retrospective study recruited 1320 COVID‐19 patients admitted to hospital from February 5, 2020, to March 9, 2020. On the basis of the presence of GI symptoms, the sample was divided into a GI group (n=192) and a non‐GI group (n=1128). The most common GI symptoms were diarrhea (8.1%), anorexia (4.7%), and nausea and vomiting (4.3%). The risk of clinical deterioration was significantly higher in the GI group than in the non‐GI group (15.6% vs. 10.1%, p=0.032). GI symptoms (p=0.045), male gender (p<0.001), and increased C‐reactive protein (p=0.008) were independent risk factors for clinical worsening. CONCLUSION: The risk of clinical deterioration was significantly higher in the GI group. Furthermore, potential risk factors for developing GI symptoms, male gender, and increased C‐reactive protein can help clinicians predict clinical outcomes in COVID‐19 patients. This article is protected by copyright. All rights reserved.


title: Evolution and emergence of novel human infections

text: Some zoonotic pathogens cause sporadic infection in humans but rarely propagate further, while others have succeeded in overcoming the species barrier and becoming established in the human population. Adaptation, driven by selection pressure in human hosts, can play a significant role in allowing pathogens to cross this species barrier. Here we use a simple mathematical model to study potential epidemiological markers of adaptation. We ask: under what circumstances could ongoing adaptation be signalled by large clusters of human infection? If a pathogen has caused hundreds of cases but with little transmission, does this indicate that the species barrier cannot be crossed? Finally, how can case reports be monitored to detect an imminent emergence event? We distinguish evolutionary scenarios under which adaptation is likely to be signalled by large clusters of infection and under which emergence is likely to occur without any prior warning. Moreover, we show that a lack of transmission never rules out adaptability, regardless of how many zoonoses have occurred. Indeed, after the first 100 zoonotic cases, continuing sporadic zoonotic infections without onward, human-to-human transmission offer little extra information on pathogen adaptability. Finally, we present a simple method for monitoring outbreaks for signs of emergence and discuss public health implications.


Transforming Positive Pressure Interventional Radiology Suites to Treat COVID-19 Patients


title: Chapter 36 Disseminated Infections A Clinical Overview

text: The ability of microorganisms to cause infection is governed by multiple different factors – some linked to the microorganisms itself and others to the host or environment. In this chapter we explore some of these factors and provide an overview of disseminated infections examining some important manifestations such as toxic shock syndrome and sepsis as well as examining some of molecular aspects including host receptors and bacterial antigens. A brief discussion will also follow about disseminated infections in specific populations such as neonates and the immunosuppressed.


title: Role of Teleproctoring in Challenging and Innovative Structural Interventions Amidst the COVID-19 Pandemic and Beyond

text: Abstract Teleproctoring can be used successfully in performing challenging and innovative structural heart interventions using sophisticated technology which allows real time bidirectional audiovisual communication with digital transmission of live videos and direct observation of the operative field by a remote proctor. We share an illustrative case that was performed amidst the COVID-19 global pandemic that led to travel restrictions to limit spread of the virus. Teleproctoring has future implications beyond the current global health crisis to facilitate rapid dissemination and exchange of knowledge for ultimately helping patients around the globe.


Frailty in the Face of COVID-19


title: Anxiety and coping strategies among nursing students during the covid-19 pandemic

text: Anxiety is highly prevalent among nursing students even in normal circumstances. In Israel during the covid-19 pandemic and mandatory lockdown, nursing students encountered a new reality of economic uncertainty, fear of infection, challenges of distance education, lack of personal protection equipment (PPE) at work etc. The objective of this study was to assess levels of anxiety and ways of coping among nursing students in the Ashkelon Academic College, Southern District, Israel. A cross-sectional study was conducted among all 244 students in the nursing department during the third week of a national lockdown. Anxiety level was assessed using the Generalized Anxiety Disorder 7-Item Scale with a cut-off point of 10 for moderate and of 15 for severe anxiety. Factor analysis was used to identify coping components. The prevalence of moderate and severe anxiety was 42.8% and 18.1% respectively. Gender, lack of PPE, parental status, and fear of infection were significantly associated with a higher anxiety score. Stronger self-esteem and usage of humor were associated with significantly lower anxiety levels, while mental disengagement with higher anxiety levels. The nursing department's staff may contribute in lowering student anxiety by staying in contact with students and encouraging and supporting them through this challenging period.


title: Chapter 53 Virus Infection of Airway Epithelial Cells

text: Abstract The airway epithelial cell barrier serves as the main site of replication for most of the common respiratory viruses and is thereby the first line of defense against these viruses. Host epithelial cells are specially enriched for pattern recognition receptors that activate immune response genes to limit viral replication. A prominently expressed set of these genes encodes cytokines that orchestrate key aspects of host defense, such as recruitment of immune cells and repair of epithelial cell damage. Under some circumstances, airway epithelial cells may be programmed to release cytokines (notably IL-33) that activate a type 2 immune response, which in excess might contribute to the development of chronic obstructive lung disease. Moreover, long-term epithelial progenitor cells with this capability may explain an ongoing susceptibility to lung disease in response to acute respiratory infection or other types of inhaled danger signals. The mucosal airway epithelial cell can thereby mediate a beneficial response for host defense and a detrimental response leading to inflammatory disease.


title: Information and Disinformation: Social Media in the COVID‐19 Crisis

text: The novel coronavirus disease of 2019 (COVID‐19) is a global pandemic with over 4.7 million cases and 316,000 deaths worldwide.(1) Social media, defined as “electronic communication through which users create online communities to share information, ideas, personal messages, and other content,”(2) has played an important role during the COVID‐19 pandemic. In fact, social media usage amongst the public has previously been demonstrated to significantly increase in cases of natural disasters and crises.(3) However, it is important to consider the benefits and limitations of this medium.


title: Association of extended dosing intervals or delays in pembrolizumab-based regimens with survival outcomes in advanced non-small cell lung cancer

text: BACKGROUND: Besides modeling/simulation-based analysis, no post-approval studies have evaluated optimal administration frequency of pembrolizumab in non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: We performed a multicenter retrospective cohort study to evaluate association between survival outcomes and treatment extensions/delays of pembrolizumab-based regimens in advanced NSCLC patients. Those who had received at least four cycles in routine practice were divided into two groups: non-standard (Non-Std: ≥2 cycles at intervals >3weeks +3days) and standard (Std: all cycles every 3weeks or 1 cycle >3weeks +3days). RESULTS: Among 150 patients, 92 (61%) were eligible for the study (Non-Std:27, Std:65). Reasons for patients with extensions/delays in the Non-Std group included: immune-related adverse events (irAEs,33%), non-irAE-related medical issues (26%), and patient-physician preference (41%). Non-Std group was more likely to have higher PD-L1 tumor proportion score, higher number of treatment cycles and pembrolizumab monotherapy. Univariate and 6-month landmark analyses showed longer median overall survival (OS) and progression-free survival (PFS) in Non-Std group compared to the Std group. After multivariable adjustment for confounding factors, there was no significant difference in OS [HR 1.2 (95%C.I.: 0.3–4.8), p=0.824] or PFS [HR 2.6 (95%C.I.: 0.7–9.6), p=0.157] between the two groups. CONCLUSION: Our study shows that a significant proportion of advanced NSCLC patients receive pembrolizumab-based regimens with extended intervals or delays in routine clinical practice and with similar outcomes to those receiving treatment at label-specified 3-week intervals. Given the durability of benefit seen and the potential for cost reduction and decreased infusion frequency in these patients, this requires validation in prospective trials.


title: Trying Times and Trying Out Solutions: Intimate Partner Violence Screening and Support for Women Veterans During COVID-19

text: Initial reports indicate widespread increases in intimate partner violence (IPV) rates during the coronavirus disease 2019 (COVID-19) pandemic. Women veterans are at particular risk for experiencing IPV, and the COVID-19 pandemic and resulting stay-at-home orders may be exacerbating this risk. IPV screening and intervention are an integral part of the care provided to women veterans in the Veteran’s Health Administration (VHA). Current changes in healthcare delivery during COVID-19 may present challenges to the VHA’s standard methods of initiating IPV screening and intervention with women veterans. We discuss the potential challenges VHA healthcare providers may be encountering when conducting routine IPV screening during the COVID-19 pandemic and when providing resources and support to women veterans experiencing IPV. We describe solutions to these challenges, including existing efforts led by the VHA IPV Assistance Program (IPVAP) as well as additional potential solutions. New ideas and partnerships will be critical for helping the VHA continue to assist women veterans experiencing IPV as the COVID-19 pandemic evolves. Though our focus is on women veterans and the VHA, the challenges and solutions we discuss are likely applicable to other populations experiencing IPV and other health care systems screening for IPV.


title: Prevention in COVID-19 time: from failure to future

text: The COVID-19 pandemic has developed as a consequence of sheer prevention failures, leading in many countries to a sizeable number of deaths and over-saturation of intensive care units. This triggered the imposition of generalisd quarantine (‘lockdown’) of variable stringency in different countries: with the decrease of the epidemic, the lockdown is now gradually relaxed and replaced by tight tracing and isolation of new cases and their contacts. Prevention, however, remains not a constant priority, as the objective may be avoidance of saturation of intensive care beds or more generally of healthcare facilities rather than the minimisation of the disease incidence. This combined with the fact that notwithstanding repeated warnings in past years the epidemic occurred as a surprise denotes a way of thinking in which prevention is an important option but not a guiding principle of choice and action within the health system. To modify this way of thinking and place prevention at the core of the system, non-negligible changes are required: they may become possible in light of emerging hazards like new viruses and climate change, huge economic costs of failed prevention and initial changes in the health system already induced by the COVID-19 epidemic.


title: Nearly full-length genome sequence of a novel astrovirus isolated from chickens with ‘white chicks’ condition

text: Avian astroviruses (aAstVs) are divided into three species, Avastrovirus 1, Avastrovirus 2, and Avastrovirus 3, but there are a few strains are waiting to be assigned to an official taxonomic group. This study presents the molecular characterization of chicken astrovirus (CAstV), PL/G059/2014, which is involved in the induction of “white chicks” condition. The 7382-nucleotide-long genome sequence was determined by next-generation sequencing using an Illumina MiSeq System. Phylogenetic analysis showed that it has the characteristics that are typical of avian astroviruses. However, overall degree of nucleotide sequence identity was 43.6 % to 73.7 % between PL/G059/2014 and other available genome sequences of aAstV strains. The amino acid sequences of the proteins encoded by ORF1a and ORF1b of the studied strain were very similar (86.5-93.8 % identity) to those of CAstVs 4175 and GA2011, but they were only 32.7-35.2 % identical in the case of ORF2, which is used officially for astrovirus species demarcation. These features could suggest that the PL/G059/2014 strain should be assigned to a new species in the genus Avastrovirus. Moreover, the different phylogenetic topology of PL/G059/2014 and its nucleotide sequence similarity in different genomic regions could suggest that a recombination event occurred during its evolution and that it has ancestors in common with duck astroviruses.


title: The perpetuation and epidemic recurrence of communicable diseases in human populations

text: Abstract Recurrence of communicable diseases is a looming threat for human populations. Factors explaining the recurrences are partially known, involving demographics, biology, and complex relationships with the environment, but no comprehensive theory exists today. Here, we review some recent results obtained in modelling studies with a view to understanding better the mechanisms of perpetuation. Factors intrinsic to the interaction of pathogen and host have regained interest in this respect, especially with multiple pathogen and multiple population interactions. Extrinsic factors, including pure demography and environmental forcing are also strong predictors. With increasingly detailed data available, large-scale integrated models will help sorting out the multiple influences on recurrence. To cite this article: P.-Y. Boëlle, C. R. Biologies 330 (2007).


title: Economic thoughts on COVID‐19 for Canadian food processors

text: In this paper, I explore the potential effects of the COVID‐19 pandemic on Canadian food processors. First, COVID‐19 may have an impact on food processing economic activities because of supply and demand shocks. Second, the impact of COVID‐19 on food processing may depend on the type of products and the size of the processors. The effects of measures taken by the government to flatten the epidemiological curve on the economic activities of the food processing sector are uncertain.


title: Of chloroquine and COVID-19

text: Abstract Recent publications have brought attention to the possible benefit of chloroquine, a broadly used antimalarial drug, in the treatment of patients infected by the novel emerged coronavirus (SARS-CoV-2). The scientific community should consider this information in light of previous experiments with chloroquine in the field of antiviral research.


title: Respiratory Distress in Postanesthesia Care Unit: First Presentation of Coronavirus Disease 2019 in a 17-Year-Old Girl: A Case Report

text: A 17-year-old healthy girl underwent an uneventful esthetic septorhinoplasty. She was easily extubated and transferred to the postanesthesia care unit (PACU) with oxygen saturation (Spo(2)) of 96%. About 30 minutes after arrival in the PACU, she developed dyspnea with Spo(2) of 84% and promptly received oxygen with bilevel positive airway pressure in conjunction with low-dose corticosteroid. The subsequent chest computed tomography (CT) revealed bilateral patchy infiltrates similar to the radiologic findings of Coronavirus Disease 2019 (COVID-19). Finally, a reverse transcriptase polymerase chain reaction (RT-PCR) of a pharyngeal specimen confirmed the diagnosis of COVID-19.


title: Population‐based study showed that necrotising enterocolitis occurred in space–time clusters with a decreasing secular trend in Sweden

text: AIM: This study investigated space–time clustering of neonatal necrotising enterocolitis over three decades. METHODS: Space–time clustering analyses objects that are grouped by a specific place and time. The Knox test and Kulldorff's scan statistic were used to analyse space–time clusters in 808 children diagnosed with necrotising enterocolitis in a national cohort of 2 389 681 children born between 1987 and 2009 in Sweden. The municipality the mother lived in and the delivery hospital defined closeness in space and the time between when the cases were born – seven, 14 and 21 days – defined closeness in time. RESULTS: The Knox test showed no indication of space–time clustering at the residential level, but clear indications at the hospital level in all the time windows: seven days (p = 0.026), 14 days (p = 0.010) and 21 days (p = 0.004). Significant clustering at the hospital level was found during 1987–1997, but not during 1998–2009. Kulldorff's scan statistic found seven significant clusters at the hospital level. CONCLUSION: Space–time clustering was found at the hospital but not residential level, suggesting a contagious environmental effect after delivery, but not in the prenatal period. The decrease in clustering over time may reflect improved routines to minimise the risk of contagion between patients receiving neonatal care.


title: A preliminary evaluation on the efficacy of ozone therapy in the treatment of COVID‐19

text: Currently, coronavirus disease 2019 (COVID‐19) is a global pandemic disease with significant morbidity and mortality. Ozone may exert its antiviral actions and ozone therapy has been demonstrated therapeutically usefulness in influenza and novel viruses. In this letter, two severe cases with COVID‐19 received ozone therapy were described. The results showed that ozone therapy may promote recovery of clinical condition and improvement of chest CT images, shorten the duration of viral shedding and length of hospital stay. This article is protected by copyright. All rights reserved.


title: A Molecularly Imprinted Polymer-Based Technology for Rapid Testing of COVID-19

text: The outbreak of COVID-19 has taken a large number of lives since 2019 and the death toll continues to increase all over the world. Recent data reports that about 27 lacs of people are infected with this virus till date and around 2 lacs are dead due to this pandemic. The situation in India is no way better. In India, almost all the states have become victim of this deadly pandemic. Considering the enormous population in India, citizens here are facing acute shortage of detection kits and many are dying even before the knowledge of their infection. The present treatise proposes a molecularly imprinted polymer (MIP) based technique for simple and rapid detection of COVID-19. The technique will be inexpensive, selective, reusable and easy to handle. It has been already implemented in our laboratory in order to detect the taste contributing agents found in tea. This article discusses the detailed methodology and the resultant analytical characteristic of the sensors developed so far and also outlines the suitability of the MIP technique towards fabrication of testing kits for rapid detection of COVID-19.


title: Predominance of Human Bocavirus Genotype 1 and 3 in Outpatient Children with Diarrhea from Rural Communities in South Africa, 2017–2018

text: Human bocavirus (HBoV) is an emerging virus globally associated with diarrhea in young children. This study aims to investigate the prevalence of HBoV genotypes in children (≤5 years) from rural communities in South Africa (SA) suffering from acute gastroenteritis (AGE). A total of 141 fecal samples of children ≤5 years with acute gastroenteritis (AGE) were collected from rural primary health care facilities in the Vhembe district of SA between June 2017 and July 2018. Clinical symptoms and demographic data were also recorded. A total of 102 (72%) were outpatients, and 39 (28%) were hospitalized patients. Human bocavirus (HBoV) genotypes were determined using real-time multiplex PCR. DNA extracts of positive samples were confirmed by conventional PCR targeting the NS1 gene. Co-infection with other enteric viruses were determined in HBoV-positive samples using real-time PCR. HBoV was detected in eight (5.7%) children with AGE, of which three (37.5%) were HBoV1, three (37.5%) were HBoV3, and two (25%) were HBoV2. The majority of positive cases were identified in outpatients (62%) between the ages of 1 and 24 months. Co-infection in HBoV-positive samples with other enteric viruses included rotavirus (37.5%), adenovirus (37.5%), norovirus (25%), and astrovirus (12.5%). HBoV infections could be seen as a potential emerging diarrheal pathogen in South Africa. However, more studies are needed to understand the role of HBoV infections in children with AGE.


title: SARS‐CoV2 and immunosuppression: a double‐edged sword

text: Severe acute respiratory syndrome Coronavirus 2 (SARS‐Cov2) outbreak has caused a pandemic rapidly impacting on the way of life of the entire world. This impact in the specific setting of transplantation and immunosuppression has been poorly explored to date. Discordant data exist on the impact of previous coronavirus outbreaks on immunosuppressed patients. Overall, only a very limited number of cases have been reported in literature, suggesting that transplanted patients not necessarily present an increased risk of severe SARS‐Cov2‐related disease compared to the general population. We conducted a literature review related to the impact of immunosuppression on coronavirus infections including case reports and series describing immunosuppression management in transplant recipients. The role of steroids, calcineurin inhibitors and mycophenolic acid has been explored more in detail. A point‐in‐time snapshot of the yet released literature and some considerations in relation to the use of immunosuppression in SARS‐Cov2 infected transplant recipients are provided here for the physicians dealing with immunocompromised patients.


title: Psychological impact of the COVID-19 pandemic on healthcare workers: a cross-sectional study in China

text: BACKGROUND: Healthcare workers fighting against the coronavirus disease 2019 (COVID-19) pandemic are under tremendous pressure, which puts them at an increased risk of developing psychological problems. AIMS: This study aimed to investigate the prevalence of psychological problems in different healthcare workers (ie, physicians, medical residents, nurses, technicians and public health professionals) during the COVID-19 pandemic in China and explore factors that are associated with the onset of psychological problems in this population during this public health crisis. METHODS: A cross-sectional, web-based survey was conducted in February 2020 among healthcare workers during the COVID-19 pandemic. Psychological problems were assessed using the Generalized Anxiety Disorder Scale, Patient Health Questionnaire and Insomnia Severity Index. Logistic regression analyses were used to explore the factors that were associated with psychological problems. RESULTS: The prevalence of symptoms of anxiety, depression, insomnia and the overall psychological problems in healthcare workers during the COVID-19 pandemic in China was 46.04%, 44.37%, 28.75% and 56.59%, respectively. The prevalence of the overall psychological problems in physicians, medical residents, nurses, technicians and public health professionals was 60.35%, 50.82%, 62.02%, 57.54% and 62.40%, respectively. Compared with healthcare workers who did not participate in front-line work, front-line healthcare workers had a higher risk of anxiety, insomnia and overall psychological problems. In addition, attention to negative or neutral information about the pandemic, receiving negative feedback from families and friends who joined front-line work, and unwillingness to join front-line work if given a free choice were three major factors for these psychological problems. CONCLUSIONS: Psychological problems are pervasive among healthcare workers during the COVID-19 pandemic. Receiving negative information and participating in front-line work appear to be important risk factors for psychological problems. The psychological health of different healthcare workers should be protected during the COVID-19 pandemic with timely interventions and proper information feedback.


title: Serological and Molecular Surveillance of Infectious Bronchitis Virus Infection in Free-Range Chickens and Guinea Fowls in the Ga-East District of Ghana

text: Infectious bronchitis is an economically important disease with worldwide distribution. Information is available on the presence of infectious bronchitis virus in commercial chicken in parts of Ghana but there is no information on free-range poultry and guinea fowls in the country. Possible IBV infections among free-range chickens and guinea fowls in Abokobi and Frafraha communities in the Ga-East district of the Greater Accra Region of Ghana were investigated using serology and PCR. Blood, tracheal, and cloacal swabs were obtained from 219 free-range chickens and guinea fowls with no respiratory symptoms and no history of IBV vaccination. Sera were evaluated for IBV antibodies by ELISA using commercial IBV test kit from IDEXX, Inc., USA. Swab samples were evaluated for S1 glycoprotein gene by one-step RT PCR. All the swab samples tested negative for IBV. 16% of all tested sera were positive for IBV. IBV seroprevalence in guinea fowls was 0%. 21.2% of sera from local chickens were positive for IBV. The seroprevalence of IBV among local chickens from Frafraha was 30% and that of Abokobi was 7.7%. This study shows exposure of local chickens in the study communities to IBV.


title: Structural Stability of Optofluidic Nanostructures in Flow-Through Operation

text: Optofluidic sensors based on periodic arrays of subwavelength apertures that support surface plasmon resonance can be employed as both optical sensors and nanofluidic structures. In flow-through operation, the nanoapertures experience pressure differences across the substrate in which they are fabricated, which imposes the risk for structural failure. This work presents an investigation of the deflection and structural stability of nanohole array-based optofluidic sensors operating in flow-through mode. The analysis was approached using experiments, simulations via finite element method, and established theoretical models. The results depict that certain areas of the sensor deflect under pressure, with some regions suffering high mechanical stress. The offset in the deflection values between theoretical models and actual experimental values is overturned when only the effective area of the substrate, of 450 µm, is considered. Experimental, theoretical, and simulation results suggest that the periodic nanostructures can safely operate under trans-membrane pressures of up to 20 psi, which induce deflections of up to ~20 μm.


title: Chapter 4 The middle east respiratory syndrome coronavirus respiratory infection: an emerging infection from the arabian peninsula

text: Abstract Middle East Respiratory Syndrome coronavirus (MERS-CoV) was initially isolated from a patient who was admitted to a private hospital in the Western part of the Kingdom of Saudi Arabia in 2012. Subsequently, MERS-CoV resulted in many sporadic cases, multiple intrafamilial transmission, and major outbreaks in healthcare settings. Of all the cases reported within the Kingdom of Saudi Arabia, 38% of the cases were primary, 45% were healthcare-associated infection, and 14% were household infections. The clinical spectrum of the MERS-CoV infection ranges from asymptomatic infections, mild or moderately symptomatic cases, and severe disease requiring intensive care unit admissions and may result in death. Within healthcare settings, transmissions of MERS-CoV are facilitated by overcrowding, poor infection control measures, unrecognized infections, and superspreader phenomenon. Currently, there is no approved therapy for MERS-CoV and there are no vaccines.


title: Detection of the Influenza A(H1N1)pdm09 Virus Carrying the K-15E, P83S and Q293H Mutations in Patients Who Have Undergone Bone Marrow Transplant

text: The 2009 pandemic influenza A(H1N1)pdm09 virus emerged and caused considerable morbidity and mortality in the third world, especially in Brazil. Although circulating strains of A(H1N1)pdm09 are A/California/04/2009-like (CA-04-like) viruses, various studies have suggested that some mutations in the viral hemagglutinin (HA) may be associated with enhanced severity and fatality. This phenomenon is particularly challenging for immunocompromised individuals, such as those who have undergone bone marrow transplant (BMT), because they are more likely to display worse clinical outcomes to influenza infection than non-immunocompromised individuals. We studied the clinical and viral aspects of post-BMT patients with confirmed A(H1N1)pdm09 diagnosis in the largest cancer hospital in Brazil. We found a viral strain with K-15E, P83S and Q293H polymorphisms in the HA, which is presumably more virulent, in these individuals. Despite that, these patients showed only mild symptoms of infection. Our findings complement the discovery of mild cases of infection with the A(H1N1)pdm09 virus with the K-15E, P83S and Q293H mutations in Brazil and oppose other studies that have linked these changes with increased disease severity. These results could be important for a better comprehension of the impact of the pandemic influenza in the context of BMT.


title: Prognostic Factors for Severe Acute Respiratory Syndrome: A Clinical Analysis of 165 Cases

text: This study analyzes single factors that affect the prognosis of severe acute respiratory syndrome (SARS) and establishes a prognosis model by multivariate analysis. We retrospectively analyzed the clinical features of SARS in 165 clinically confirmed severe cases. Both age and existence of other diseases before SARS were significantly correlated with prognosis (r = 0.506 and r = 0.457, respectively; P < .001). During the acute phase of SARS, lactate dehydrogenase level, degree of hypoxemia, respiratory rate, α-hydroxybutyric dehydrogenase level, creatine kinase isoenzyme—MB, platelet count, and number of involved lobes noted on chest radiographs, and so on, correlated markedly with the prognosis (r = 0.257–0.788; P < .05). The multivariate prognosis regression model was associated with degree of hypoxemia and platelet count. The model was defined by the formula P(y=1) = e(s)/(1 + e(s)), where S is [2.490 × degree of hypoxemia]-[0.050 × number of platelets], and it had a high sensitivity (91.67%), specificity (98.33%), and accuracy (96.42%). The model could be used to effectively judge the state of illness and the prognosis.


Social scientific knowledge in times of crisis: What climate change can learn from coronavirus (and vice versa)


title: Controversies in the management of acute tonsillitis: an evidence‐based review

text: BACKGROUND: Patients admitted with acute tonsillitis generate a substantial workload for the National Health Service (NHS), placing huge financial pressures on an already overstretched budget. OBJECTIVE OF REVIEW: Due to the difficulty of accurate diagnosis and varying practices across the UK, there exist a number of controversial areas and non‐standardised practice. These will be highlighted and tackled within this article. TYPE OF REVIEW AND SEARCH STRATEGY: A literature review, last performed in September 2013, searched PubMed citing variations on the areas of controversies with ‘tonsillitis’, ‘pharyngitis’ and ‘pharyngotonsillitis’ – from 1956 to present with language restrictions. Excluded articles included those regarding sore throat after tonsillectomy and peritonsillar abscess. EVALUATION METHOD: Titles and abstracts were initially screened, and full text of potentially relevant articles obtained. The bibliographies of articles were searched for relevant references. The references were then compiled and reviewed independently by two authors (JB & TB), overseen by the senior author (EK). RESULTS: (i) Diagnosis and investigation: Use of the Centor criteria is inadequate within the secondary care setting. Blood testing is unnecessary in the majority of cases where patients do not require admission, as they are unlikely to change management. (ii) Antibiotics: Antibiotics are likely to be indicated in all those presenting to secondary ENT care, with penicillin being the antibiotic of choice for first‐line therapy. (iii) Corticosteroids: Moderate evidence supports the benefit of steroid administration in this patient cohort, advocating a single dose initially followed by reassessment. (iv) Analgesia: Paracetamol and NSAIDs have good evidence of action. Codeine should be used with caution in the paediatric population. (v) Reduced admission rates and early discharge: There is evidence suggesting that a trial of medical therapy prior to admission is beneficial in reducing rates of admission and length of stay. CONCLUSIONS: Management of acute tonsillitis within a secondary care setting largely consists of anecdotal or relatively low‐quality evidence. Thus, much evidence from management comes from expert opinion or practice within a primary care setting. Management across the UK can also vary greatly. An evidence‐based review of best practice has been presented here, but further evidence will be required in the future examining the significance of corticosteroids and antibiotic administration in this patient cohort specifically, ensuring practice is evidence based and clinically relevant.


title: Porcine Anti-viral Immunity: How Important Is It?

text: Pork has become the number one meat consumed worldwide. Meeting the demand for pork has forced the revolution of swine production from traditional husbandry practices that involved a few pigs or small herds to intensive concentration of swine raised in multisite production systems. This dramatic change has made the production of pork very efficient, but it has also changed the ecology of many swine diseases, may encourage the emergence of new diseases, and amplifies the economic impact of swine diseases. Sustained treatment of diseases in livestock production is not feasible making prevention of disease a priority. Prevention of livestock diseases involves eliminating exposure to pathogens and anti-viral strategies to prevent or reduce clinical disease. For some swine diseases, efficacious vaccines can be made, however, for other diseases the host/pathogen relationship is more complex and efficacious vaccines are not available. Given the increasing demand for pork, the development of new approaches to improve swine anti-viral immunity is critical. Rate-limiting steps to improving vaccines are understanding how the pathogen interacts with the host's immune system, any immunopathology resulting from such interactions and how the host's immune system resolves the infection. Solving this puzzle will require sustained research and may require new technologies to battle contemporary diseases now wreaking havoc in swine production systems around the world. This Special Issue will focus on current swine viral diseases that are the most challenging to the global production of pork with contributions focusing on anti-viral immunity.


title: The Dual Role of TNF in Pulmonary Edema

text: —Pulmonary edema, a major manifestation of left ventricular heart failure, renal insufficiency, shock, diffuse alveolar damage and lung hypersensitivity states, is a significant medical problem worldwide and can be life-threatening. The proinflammatory cytokine tumor necrosis factor (TNF) has been shown to contribute to the pathogenesis and development of pulmonary edema. However, some recent studies have demonstrated surprisingly that TNF can also promote alveolar fluid reabsorption in vivo and in vitro. This protective effect of the cytokine is mediated by the lectin-like domain of the cytokine, which is spatially distinct from the TNF receptor binding sites. The TIP peptide, a synthetic mimic of the lectin-like domain of TNF, can significantly increase alveolar fluid clearance and improve lung compliance in pulmonary edema models. In this review, we will discuss the dual role of TNF in pulmonary edema. ABBREVIATIONS: —tumor necrosis factor (TNF); acute lung injury (ALI); acute respiratory distress syndrome (ARDS); positive end-expiratory pressure (PEEP);epithelial sodium channel (ENaC);neural precursor cell-expressed developmentally downregulated (gene 4) protein (Nedd4-2);serum and glucocorticoid dependent kinase (Sgk-1);insulin-like growth factor 1 (IGF-1);Protein Kinase C (PKC);reactive oxygen species (ROS);myosin light chain (MLC);pneumolysin (PLY);listeriolysin (LLO);interleukin (IL);bronchoalveolar lavage fluids (BALF);Bacillus Calmette-Guerin (BCG);TNF receptor type 1 (TNFR1); TNF receptor type 2 (TNF-R2);


Is physiotherapy ready for the management of COVID‐19 in Africa? – Snippets of anecdotal evidences in two African countries


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title: Lack of cross-protection against Mycoplasma haemofelis infection and signs of enhancement in “Candidatus Mycoplasma turicensis”-recovered cats

text: “Mycoplasma haemofelis” and “Candidatus Mycoplasma turicensis” are feline hemoplasmas that induce hemolytic anemia. Protection from homologous re-challenge was recently demonstrated in cats recovered from primary infection. Here, we determined if cats recovered from “Cand. M. turicensis” infection were protected against infections with the more pathogenic M. haemofelis. Ten specified pathogen-free cats were exposed to M. haemofelis. Five of the ten cats had recovered from “Cand. M. turicensis” bacteremia (group A), and five cats were naïve controls (group B). No cross-protection was observed. By contrast, the “Cand. M. turicensis”-recovered cats displayed faster M. haemofelis infection onset (earlier PCR-positive and anemic) than the controls. No “Cand. M. turicensis” was detected in any cat. M. haemofelis shedding was observed in saliva, feces and urine. In both groups, evidence of a Th1 response was observed (high IFN-γ, low IL-4), but IL-10 levels were also high. In group A, total, CD4+ and CD8+ T cells increased within days after M. haemofelis exposure. At times of maximal bacteremia, macrocytic hypochromic anemia, neutropenia, monocytosis and a decrease in leukocyte, eosinophil, and lymphocyte counts and subsets thereof (B- and T-cells, CD4+, CD8+ and CD4+CD25+ cells) were particularly significant in group A. Moreover, an increase in protein concentrations, hypoalbuminemia and a polyclonal hypergammaglobulinemia were observed. Five of ten M. haemofelis-infected cats subsequently cleared bacteremia without antibiotic treatment. In conclusion, the study suggests that a previous hemoplasma infection, even when the cat has ostensibly recovered, may influence subsequent infections, lead to an enhancement phenomenon and other differences in infection kinetics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-015-0240-x) contains supplementary material, which is available to authorized users.


title: A Proposal for Staging COVID‐19 Coagulopathy

text: COVID‐19 is associated with significant hypercoagulability. However, despite prophylactic anticoagulation, critically‐ill patients with this condition develop thromboses. This forum discusses the lungs as the epicentre for the haemostatic issues, put forwards a proposal for staging COVID‐19 coagulopathy based on available diagnostic markers, and suggest considering current and future treatment options based on these different stages.


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title: Chapter 26 The Molecular Libraries Screening Center Network (MLSCN): Identifying Chemical Probes of Biological Systems

text: Publisher Summary The NIH Molecular Libraries Screening Center Network (MLSCN) is a subset of the Molecular Libraries Initiative (MLI) component of the NIH Roadmap for Medical Research. The ultimate goal of the MLSCN and the MLI is to expand the availability, flexibility, and use of small-molecule chemical probes for basic research. A number of aspects of the MLSCN make this initiative unique from other academic screening center. First, all researchers have access to the screening centers through the NIH X01 and R03 funding mechanisms. Second, because of the diverse source of assays and the wide expertise available within the MSLCN, specific biological systems investigated and screened will include: (1) “high risk” targets—that is, proteins or biological systems whose function is unknown; (2) targets implicated in orphan diseases or diseases not typically addressed by the private sector; (3) novel or uncommon assay systems; and (4) “non-druggable” targets, such as inhibitors of aggregation and protein–protein interactions. Third, the small molecule screening library contains structures not typically found in commercial collections or those housed in pharmaceutical companies. Fourth, as the goal of the MLSCN is to develop selective chemical probes and small molecule tools that will interrogate novel biochemical pathways, the criteria for an acceptable class of molecules is broader for the MLSCN than for those involved in drug discovery and development. Fifth, is the inclusion of integral medicinal chemistry within each MLSCN Center that allows the network to produce chemical probes with particular properties, rather than simply identifying apparent activities from the screening collection.


title: Biological Materials: The Next Frontier for Cell-Free Synthetic Biology

text: Advancements in cell-free synthetic biology are enabling innovations in sustainable biomanufacturing, that may ultimately shift the global manufacturing paradigm toward localized and ecologically harmonized production processes. Cell-free synthetic biology strategies have been developed for the bioproduction of fine chemicals, biofuels and biological materials. Cell-free workflows typically utilize combinations of purified enzymes, cell extracts for biotransformation or cell-free protein synthesis reactions, to assemble and characterize biosynthetic pathways. Importantly, cell-free reactions can combine the advantages of chemical engineering with metabolic engineering, through the direct addition of co-factors, substrates and chemicals –including those that are cytotoxic. Cell-free synthetic biology is also amenable to automatable design cycles through which an array of biological materials and their underpinning biosynthetic pathways can be tested and optimized in parallel. Whilst challenges still remain, recent convergences between the materials sciences and these advancements in cell-free synthetic biology enable new frontiers for materials research.


title: Synthesis, modification and docking studies of 5-sulfonyl isatin derivatives as SARS-CoV 3C-like protease inhibitors

text: Abstract The Severe Acute Respiratory Syndrome (SARS) is a serious life-threatening and strikingly mortal respiratory illness caused by SARS-CoV. SARS-CoV which contains a chymotrypsin-like main protease analogous to that of the main picornavirus protease, 3CLpro. 3CLpro plays a pivotal role in the viral replication cycle and is a potential target for SARS inhibitor development. A series of isatin derivatives as possible SARS-CoV 3CLpro inhibitors was designed, synthesized, and evaluated by in vitro protease assay using fluorogenic substrate peptide, in which several showed potent inhibition against the 3CLpro. Structure–activity relationship was analyzed, and possible binding interaction modes were proposed by molecular docking studies. Among all compounds, 8k1 showed most potent inhibitory activity against 3CLpro (IC50 =1.04μM). These results indicated that these inhibitors could be potentially developed into anti-SARS drugs.


title: The small envelope protein of porcine reproductive and respiratory syndrome virus possesses ion channel protein-like properties

text: Abstract The small envelope (E) protein of porcine reproductive and respiratory syndrome virus (PRRSV) is a hydrophobic 73 amino acid protein encoded in the internal open reading frame (ORF) of the bicistronic mRNA2. As a first step towards understanding the biological role of E protein during PRRSV replication, E gene expression was blocked in a full-length infectious clone by mutating the ATG translational initiation to GTG, such that the full-length mutant genomic clone was unable to synthesize the E protein. DNA transfection of PRRSV-susceptible cells with the E gene knocked-out genomic clone showed the absence of virus infectivity. P129-ΔE-transfected cells however produced virion particles in the culture supernatant, and these particles contained viral genomic RNA, demonstrating that the E protein is essential for PRRSV infection but dispensable for virion assembly. Electron microscopy suggests that the P129-ΔE virions assembled in the absence of E had a similar appearance to the wild-type particles. Strand-specific RT-PCR demonstrated that the E protein-negative, non-infectious P129-ΔE virus particles were able to enter cells but further steps of replication were interrupted. The entry of PRRSV has been suggested to be via receptor-mediated endocytosis, and lysomotropic basic compounds and known ion-channel blocking agents both inhibited PRRSV replication effectively during the uncoating process. The expression of E protein in Escherichia coli-mediated cell growth arrests and increased the membrane permeability. Cross-linking experiments in cells infected with PRRSV or transfected with E gene showed that the E protein was able to form homo-oligomers. Taken together, our data suggest that the PRRSV E protein is likely an ion-channel protein embedded in the viral envelope and facilitates uncoating of virus and release of the genome in the cytoplasm.


title: Integration of virtual and physical screening

text: High-throughput screening (HTS) represents the dominant technique for the identification of new lead compounds in current drug discovery. It consists of physical screening (PS) of large libraries of chemicals against one or more specific biological targets. Virtual screening (VS) is a strategy for in silico evaluation of chemical libraries for a given target, and can be integrated to focus the PS process. The present work addresses the integration of both PS and VS, respectively. Section editors: Tudor Oprea – University of New Mexico School of Medicine, Albuquerque, USA Alex Tropsha – University of North Carolina, Chapel Hill, USA


COVID-19 in Puerto Rico: Perspective from an Internal Medicine Resident Physician


title: Binding interactions of niclosamide with serum proteins

text: Abstract A study of the binding of niclosamide (NC) to serum proteins such as human serum albumin, hemoglobin, and globulin was carried out using fluorescence and UV-visible spectroscopy. Interactions between NC and these proteins were estimated by Stern–Volmer and van't Hoff equations. The binding constants and the thermodynamic parameters, ΔH, ΔS, and ΔG at different temperatures were also determined by using these equations. Data showed that NC may exhibit a static quenching mechanism with all proteins. The thermodynamic parameters were calculated. Data showed that van der Waals interactions and hydrogen bonds are the main forces for human serum albumin and hemoglobin. Globulin, however, bound to NC via hydrophobic interaction. The spectral changes of synchronous fluorescence suggested that both the microenvironment of NC and the conformation of the proteins changed in relation to their concentrations during NC's binding.


Invited Commentary on the letter "The COVID-19 crisis: A unique opportunity to expand dermatology to underserved populations."


Managing Healthcare Worker Wellbeing in an Australian Emergency Department during The COVID‐19 Pandemic


title: Detection of Nucleocapsid Antibody to SARS-CoV-2 is More Sensitive than Antibody to Spike Protein in COVID-19 Patients

text: Background: SARS-CoV-2, the cause of coronavirus disease 2019 (COVID-19), is associated with respiratory-related morbidity and mortality. Assays to detect virus-specific antibodies are important to understand the prevalence of infection and the course of the immune response. Methodology: Quantitative measurements of plasma or serum antibodies by luciferase immunoprecipitation assay systems (LIPS) to the nucleocapsid and spike proteins were analyzed in 100 cross-sectional or longitudinal samples from SARS-CoV-2-infected patients. A subset of samples was tested with and without heat inactivation. Results: Fifteen or more days after symptom onset, antibodies against SARS-CoV-2 nucleocapsid protein showed 100% sensitivity and 100% specificity, while antibodies to spike protein were detected with 91% sensitivity and 100% specificity. Neither antibody levels nor the rate of seropositivity were significantly reduced by heat inactivation of samples. Analysis of daily samples from six patients with COVID-19 showed anti-nucleocapsid and spike antibodies appearing between day 8 to day 14 after initial symptoms. Immunocompromised patients generally had a delayed antibody response to SARS-CoV-2 compared to immunocompetent patients. Conclusions: Antibody to the nucleocapsid protein of SARS-CoV-2 is more sensitive than spike protein antibody for detecting early infection. Analyzing heat-inactivated samples by LIPS is a safe and sensitive method for detecting SARS-CoV-2 antibodies.


title: Safety and efficacy of a modified-live canine coronavirus vaccine in dogs

text: Abstract The safety and the efficacy of a modified-live (ML) canine coronavirus (CCoV) vaccine strain 257/98-3c was evaluated in 14 dogs seronegative and virus negative for CCoV. For the safety test, four dogs were inoculated, two by intramuscular and two by oronasal route, with 10 times the vaccinal dose. During the observation period (28 days) all dogs did not display any local or systemic reaction. For the efficacy test, eight dogs were vaccinated by intramuscular (four dogs—group A) or by oronasal route (four dogs—group B). Two dogs were maintained as non-vaccinated controls. In the dogs of group A, vaccinal virus was not detected in faecal samples by virus isolation (VI) and by PCR assay, while in the dogs of group B, the virus was revealed for six median days only by PCR. Twenty-eight days later, the vaccinated and control dogs were challenged with a field CCoV strain. After the challenge, the vaccinated dogs did not display clinical signs and the dogs of group A shed virus for 5.5 median days, evaluated by VI, and for 10 median days evaluated by PCR. Virus shedding was not observed, both by VI and PCR assay, in the dogs of group B. The two control dogs displayed moderate clinical signs and the virus was detected by VI for 14.5 median days starting from day 3 post-challenge (dpc 3) and by PCR assay for 23 median days starting from dpc 1.


title: Perspectives on challenges and opportunities for birth defects surveillance programs during and after the COVID‐19 era

text: In recent months, various public health measures have been implemented throughout the world in response to the coronavirus disease 2019 (COVID‐19) pandemic. This outbreak, and the subsequent containment policies, may have a range of potential short‐ and long‐term impacts on the monitoring and surveillance of other conditions, such as birth defects. In this commentary, we provide a perspective on these potential impacts on birth defects surveillance and analysis. We discuss possible effects on clinical birth defect diagnoses, routine birth defects surveillance system activities, and epidemiologic considerations, as well as opportunities for mitigating the impact of COVID‐19. Like many other sectors of public health and medicine, birth defects surveillance programs may be faced with organizational and methodological obstacles in the wake of a changing landscape. A better understanding of these potential challenges faced by birth defects surveillance programs could facilitate better planning and collaboration across programs to overcome barriers to core activities and to prepare for novel opportunities for research and prevention.


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title: Human coronavirus NL63 infections in infants hospitalised with acute respiratory tract infections in South Africa

text: Background Human coronavirus NL63 (HCoV‐NL63) is a novel respiratory virus which is associated with respiratory tract infections in children. Objective To determine the role of HCoV‐NL63 in infants and young children hospitalised with acute respiratory tract infections (ARI) in Cape Town, South Africa. Methods Respiratory specimens were collected from 1055 infants and young children hospitalised with ARI in 2003–2004. Samples were screened by RT‐PCR to detect HCoV‐NL63 and human metapneumovirus (hMPV). Standard shell vial culture and immunofluoresence was used to detect the common respiratory viruses including RSV, influenza A and B viruses, parainfluenza viruses 1, 2, 3, adenovirus and CMV. Results A respiratory virus was found in 401/1055 (38·0%) samples. HCoV‐NL63 was detected in 9/1055 (0·85%) with peak activity during autumn (67%). Most patients had a diagnosis of pneumonia or lower respiratory tract infection (6/9; 67%). Conclusions This is the first report of HCoV‐NL63 infections in hospitalised children in Africa. During the 2‐year period HCoV‐NL63 played a minor role in ARI in children.


title: High-Dose Mannose-Binding Lectin Therapy for Ebola Virus Infection

text: Mannose-binding lectin (MBL) targets diverse microorganisms for phagocytosis and complement-mediated lysis by binding specific surface glycans. Although recombinant human MBL (rhMBL) trials have focused on reconstitution therapy, safety studies have identified no barriers to its use at higher levels. Ebola viruses cause fatal hemorrhagic fevers for which no treatment exists and that are feared as potential biothreat agents. We found that mice whose rhMBL serum concentrations were increased ≥7-fold above average human levels survived otherwise fatal Ebola virus infections and became immune to virus rechallenge. Because Ebola glycoproteins potentially model other glycosylated viruses, rhMBL may offer a novel broad-spectrum antiviral approach.


Metallo-β-lactamase 1 - why blame New Delhi & India?


title: Comparative pathology of pigs infected with Korean H1N1, H1N2, or H3N2 swine influenza A viruses

text: BACKGROUND: The predominant subtypes of swine influenza A virus (SIV) in Korea swine population are H1N1, H1N2, and H3N2. The viruses are genetically close to the classical U.S. H1N1 and triple-reassortant H1N2 and H3N2 viruses, respectively. Comparative pathogenesis caused by Korean H1N1, H1N2, and H3N2 SIV was evaluated in this study. FINDINGS: The H3N2 infected pigs had severe scores of gross and histopathological lesions at post-inoculation days (PID) 2, and this then progressively decreased. Both the H1N1 and H1N2 infected pigs lacked gross lesions at PID 2, but they showed moderate to severe pneumonia on PID 4, 7 and 14. The pigs infected with H1N1 had significant scores of gross and histopathological lesions when compared with the other pigs infected with H1N2, H3N2, and mock at PID 14. Mean SIV antigen-positive scores were rarely detected for pigs infected with H1N2 and H3N2 from PID 7, whereas a significantly increased amount of viral antigens were found in the bronchioles and alveolar epithelium of the H1N1infected pigs at PID 14. CONCLUSIONS: We demonstrated that Korean SIV subtypes had different pulmonary pathologic patterns. The Korean H3N2 rapidly induced acute lung lesions such as broncho-interstitial pneumonia, while the Korean H1N1 showed longer course of infection as compared to other strains.


title: Clinical practice of respiratory virus diagnostics in critically ill patients with a suspected pneumonia: A prospective observational study

text: Abstract Background Clinical guidelines suggest testing for respiratory viruses during the influenza season, but are unclear which categories of patients on the intensive care unit (ICU) should be tested. Objective We described the clinical practice of diagnostic testing for respiratory virus infections in patients presenting to ICU with suspected community-acquired pneumonia (CAP) or hospital-acquired pneumonia (HAP). Study design Prospective observational study in consecutive CAP and HAP patients with an ICU stay of more than 24h in two tertiary care hospitals in The Netherlands, from 2011 to December 2013. The proportion of patients receiving diagnostic testing with PCR for the presence of respiratory viruses in respiratory tract specimens was determined. Results In total, 1452 patients were included, of which 712 patients presented with CAP and 740 with HAP. In CAP, 282 of 712 (40%) were tested for respiratory viruses (190 of 417 (46%) during the influenza season). In HAP, 95 of 740 (13%) were tested (50 of 372 (13%) during the influenza season). Regardless of the season, virus diagnostic tests were ordered significantly more often in patients with comorbidities, and in those presenting with elevated CRP and leucopenia. In patients who were tested during the influenza season, the prevalence of influenza was 14% in patients with CAP and 10% in those with HAP. Influenza was absent during the summer in both groups. Conclusions Less than half of patients admitted to the ICU with suspected pneumonia were tested for the presence of viral pathogens, either in or outside the influenza season.


title: Eleven faces of coronavirus disease 2019

text: BACKGROUND AND AIMS: The outbreak of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has recently spread worldwide and been declared a pandemic. We aim to describe here the various clinical presentations of this disease by examining eleven cases. METHODS: Electronic medical records of 11 patients with COVID‐19 were collected, and demographics, clinical manifestations, outcomes, key laboratory results, and radiological images are discussed. RESULTS: The clinical course of the eleven cases demonstrated the complexity of the COVID‐19 profile with different clinical presentations. Clinical manifestations range from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia. Laboratory detection of the viral nucleic acid can yield false‐negative results, and serological testing of virus‐specific IgG and IgM antibodies should be used as an alternative for diagnosis. Patients with common allergic diseases did not develop distinct symptoms and severe courses. Cases with a pre‐existing condition of chronic obstructive pulmonary disease or complicated with a secondary bacterial pneumonia were more severe. CONCLUSION: All different clinical characteristics of COVID‐19 should be taken into consideration to identify patients that need to be in strict quarantine for the efficient containment of the pandemic.


title: Chapter 3 Infectious Bronchitis Virus in Poultry: Molecular Epidemiology and Factors Leading to the Emergence and Reemergence of Novel Strains of Infectious Bronchitis Virus

text: Abstract Infectious bronchitis virus (IBV) is a coronavirus that causes an acute and highly contagious disease in chickens. The virus can cause substantial economic losses throughout the poultry industry worldwide. It can affect the upper respiratory tract and the reproductive tract, and some strains can cause nephritis. The causative agent IBV is an RNA virus with great ability for mutation and recombination, thus capable of generating new virus strains that are difficult to control. There are many IBV strains found worldwide, including the Massachusetts, 4/91, D274, and QX-like strains that can be grouped under the classic or variant serotypes. In addition, new types of the virus continue to arise due to mutations and recombination events in the viral genome and even more factors, making this virus difficult to identify and extremely difficult to control. Surveillance and identification of IBV types are extremely important for control of the disease and the advancement of molecular methods has aided in this pursuit. Genetic typing of IBV, which involves reverse transcription polymerase chain reaction amplification and sequence analysis of the S1 glycoprotein gene, has revolutionized diagnosis and identification of this virus by making it possible to type and compare the relatedness of a large number of virus isolates in a short period of time. Several conventional and molecular diagnostic methods have been described for the diagnosis of IB in chickens. “All-in/all-out” operations of rearing along with good biosafety measures form the basis of prevention, whereas vaccination forms the backbone of IB control program. Both live and inactivated (oil emulsified) conventional vaccines are available. The new generation vaccines (recombinant and vector-based) developed against locally prevailing IBV strains may be more helpful and avoid the reversion of virulence in live vaccine viruses.