title: Characteristics and outcomes of oral antibiotic treated pulmonary exacerbations in children with cystic fibrosis

text: Abstract Background Pulmonary exacerbations (PEx) in children with cystic fibrosis (CF) are frequently treated in the outpatient setting with oral antibiotics. However, little is known about the characteristics of PEx managed on an outpatient basis and the effectiveness of oral antibiotic therapy. We sought to prospectively evaluate clinical and laboratory changes associated with oral antibiotic treatment for PEx. Methods Children with CF between 8 and 18 years of age prescribed two weeks of oral antibiotics for a PEx were eligible to enroll. The study consisted of a visit within 48 h of starting antibiotics and a second visit within one week of antibiotic completion. Twenty-eight participants were evaluated by exacerbation score, quality of life measurements, lung function, sputum microbiology and inflammation. Results Oral antibiotic treatment was associated with a significant improvement in exacerbation score and quality of life measured by the CF Questionnaire-Revised (CFQ-R) respiratory domain. Following treatment, forced expiratory volume in 1 s (FEV1) % predicted increased [median (range)] 9% (−8%, 31%), and 22 (81%) subjects returned to 90% or higher of baseline FEV1. Bacterial density of the primary organism identified on sputum culture decreased significantly with a median (range) decrease of 0.8 log10 cfu/mL (−8 log10, 2 log10, p = 0.03). Sputum neutrophil elastase [−37 μg/mL (−464, 272), p = 0.02] and IL-1β [−2.8 × 103μg/mL (−6.9 × 104, 3.3 × 104), p = 0.03] decreased significantly following treatment in this cohort. Conclusions Treatment of PEx with oral antibiotics was associated with measurable improvements in patient reported outcomes, lung function, bacterial density and sputum inflammatory markers.


title: Chapter 1 Nanomaterials in Biosensors Fundamentals and Applications

text: Abstract With the recent advancement of nanomaterials and nanostructured materials, the point-of-care biosensor devices have shown a potential growth to revolutionize the future personalized health care diagnostics and therapy practices. This chapter deals with the fundamentals of nanomaterials-based biosensors. The first chapter covers the brief details of nanotechnology with its types and an introduction to the synthesis of nanomaterials and their importance to construct transducers. The different components of transducers such as electrochemical, optical, piezoelectric, thermal, surface plasmon resonance, and so on for biosensors have been explained in this chapter. Various principles utilized for development of enzymatic biosensors, immunosensors, DNA, and whole-cell biosensors have been included in this chapter. Immobilization of bioreceptors is a crucial step to fabricate biosensors and their stepwise demonstration and conjugation of nanomaterials with nanomaterials have been described.


title: Effects of ribavirin on cytokine production of recall antigens and phytohemaglutinin-stimulated peripheral blood mononuclear cells. (Inhibitory effects of ribavirin on cytokine production)

text: Abstract Aim: To evaluate the effects of ribavirin on cytokine production of recall antigen and PHA-stimulated PBMC obtained from healthy individuals. Materials and methods: PBMC were challenged with tetanus toxoid (5μg/mL) and PHA (10 μmL) in absence or presence of ribavirin at different concentrations (1, 10 and 100 (μM). Parallel sets of wells containing PBMC exposed to medium alone were used as negative controls. On day 3 after initiation of the cultures, IL-2, IFN-γ, IL-4, IL-10, TNF-α content were determined in supernatants of PBMC from the different individuals. Results: The effects of ribavirin on cytokine released by human PBMC in response to PHA and TT showed a great variation among individuals. No significant changes were observed between 1-10μ M concentrations in the production of TNF-α, IFN-γ and IL-10 by both PHA and TT-stimulated PBMC. Ribavirin inhibited TNF-α, IFN-γ, and IL-10 in both PHA and TT-stimulated PBMC at 100 μM (p <0.05). At this concentration, ribavirin induced an increase of 124% in the production of IL-2 by PHA-stimulated PBMC (p <0.05). Conclusions: The present data suggest that ribavirin may cause diverse effects on immunoregulatory cytokine secretion with changes in the Th1/Th2 balance.


title: HIV virions sense plasma membrane heterogeneity for cell entry

text: It has been proposed that cholesterol in host cell membranes plays a pivotal role for cell entry of HIV. However, it remains largely unknown why virions prefer cholesterol-rich heterogeneous membranes to uniformly fluid membranes for membrane fusion. Using giant plasma membrane vesicles containing cholesterol-rich ordered and cholesterol-poor fluid lipid domains, we demonstrate that the HIV receptor CD4 is substantially sequestered into ordered domains, whereas the co-receptor CCR5 localizes preferentially at ordered/disordered domain boundaries. We also show that HIV does not fuse from within ordered regions of the plasma membrane but rather at their boundaries. Ordered/disordered lipid domain coexistence is not required for HIV attachment but is a prerequisite for successful fusion. We propose that HIV virions sense and exploit membrane discontinuities to gain entry into cells. This study provides surprising answers to the long-standing question about the roles of cholesterol and ordered lipid domains in cell entry of HIV and perhaps other enveloped viruses.


title: Translational Recoding Induced by G-Rich mRNA Sequences That Form Unusual Structures

text: Abstract We investigated a herpesvirus mutant that contains a single base insertion in its thymidine kinase (tk) gene yet expresses low levels of TK via a net +1 translational recoding event. Within this mutant gene, we defined a G-rich signal that is sufficient to induce recoding. Unlike other translational recoding events, downstream RNA structures or termination codons did not stimulate recoding, and paused ribosomes were not detected. Mutational analysis indicated that specific tRNAs or codon–anticodon slippage were unlikely to account for recoding. Rather, recoding efficiency correlated with the G-richness of the signal and its ability to form unusual structures. These findings identify a mechanism of translational recoding with unique features and potential implications for clinical drug resistance and other biological systems.


title: Genetic dissection of lymphopenia from autoimmunity by introgression of mutated Ian5 gene onto the F344 rat

text: Abstract Peripheral T cell lymphopenia (lyp) in the BioBreeding (BB) rat is linked to a frameshift mutation in Ian5, a member of the Immune Associated Nucleotide (Ian) gene family on rat chromosome 4. This lymphopenia leads to type 1 (insulin-dependent) diabetes mellitus (T1DM) at rates up to 100% when combined with the BB rat MHC RT1 u/u genotype. In order, to better study the lymphopenia phenotype without possible confounding effects of diabetes or other autoimmune disease, we generated congenic F344.lyp rats by introgression of lyp on diabetes-resistant MHC RT1 lv1/lv1 F344 rats. Analysis of thymic CD4 and CD8 T lymphocytes revealed no difference in the percentage of CD4−CD8+and CD4+CD8−subsets in lyp/lyp compared to +/+ F344 rats. The same subsets was however dramatically reduced in blood (P=0.005), spleen (P=0.019) and mesenteric lymph nodes (MLN) (P<0.0001). Compared to F344 +/+ rats double positive CD4+CD8+T cells were increased only in lyp/lyp spleen (P=0.034) while double negative CD4−CD8−were increased in thymus (P=0.033), spleen (P=0.012), MLN (P<0.0001), and peripheral blood (P<0.0001). There were no signs of inflammatory lesions in organs and tissues in F344.lyp/lyp rats examined at 120 days of age or older. We thus conclude that the lymphopenia phenotype was reconstituted by introgression of lyp on to F344 rats without subsequent development of organ-specific autoimmunity. The congenic F344.lyp rat should prove useful to dissect the mechanisms by which the Ian5 frameshift mutation affects T cell selection, differentiation and maturation without organ-specific autoimmunity.


title: Distributed data processing for public health surveillance

text: BACKGROUND: Many systems for routine public health surveillance rely on centralized collection of potentially identifiable, individual, identifiable personal health information (PHI) records. Although individual, identifiable patient records are essential for conditions for which there is mandated reporting, such as tuberculosis or sexually transmitted diseases, they are not routinely required for effective syndromic surveillance. Public concern about the routine collection of large quantities of PHI to support non-traditional public health functions may make alternative surveillance methods that do not rely on centralized identifiable PHI databases increasingly desirable. METHODS: The National Bioterrorism Syndromic Surveillance Demonstration Program (NDP) is an example of one alternative model. All PHI in this system is initially processed within the secured infrastructure of the health care provider that collects and holds the data, using uniform software distributed and supported by the NDP. Only highly aggregated count data is transferred to the datacenter for statistical processing and display. RESULTS: Detailed, patient level information is readily available to the health care provider to elucidate signals observed in the aggregated data, or for ad hoc queries. We briefly describe the benefits and disadvantages associated with this distributed processing model for routine automated syndromic surveillance. CONCLUSION: For well-defined surveillance requirements, the model can be successfully deployed with very low risk of inadvertent disclosure of PHI – a feature that may make participation in surveillance systems more feasible for organizations and more appealing to the individuals whose PHI they hold. It is possible to design and implement distributed systems to support non-routine public health needs if required.


title: COVID-19 provides an opportunity to advance a sustainable UK fisheries policy in a post-Brexit brave new world

text: Brexit creates a systemic shock that provides a unique opportunity for the UK to implement a new sustainable Fisheries Policy to better manage the multiple stocks on which future fishers will depend on leaving the European Union. At the same time, the global slowdown of commercial fishing as a result of COVID-19 has reduced pressure on some threatened stocks to levels not seen since the Second World War. In combination, Brexit and the COVID-19 slowdown have created a unique opportunity to facilitate the recovery of a threatened resource. Nevertheless, challenges remain as fisheries represent only 0.12% of UK economic output, presenting a risk that opportunities for more sustainable management will be lost during wider trade negotiations. Reduced fishing pressure during the COVID-19 era will enable stocks an opportunity to recover if supported by a new UK Fisheries Policy that focuses on: (a) re-establishing the role of Maximum Sustainable Yield to set limits that enable the recovery of fish populations initiated during the COVID-19 era; (b) ensuring that catch targets are set with the aim to maintain biomass at 120% of that which will achieve Maximum Sustainable Yield; (c) improving coherent resource management that also considers the expensive use of carbon associated with unsustainable fishing, and the need to protect fish throughout their life-cycle; and (d) constructing and effectively enforcing protection of a resilient network of Marine Protected Areas despite potential protests from EU member states.


title: The emergence of enterovirus D68 in a Dutch University Medical Center and the necessity for routinely screening for respiratory viruses

text: Abstract Background Since August 2014, an increase in infections caused by enterovirus D68 (EV-D68) was reported in the USA and Canada, for the most part in children presenting with severe respiratory symptoms. Objectives To determine whether an increase in severe EV-D68 respiratory infections was observed in our region. Study design Samples from patients with respiratory symptoms were screened for viral pathogens, including rhinovirus and enterovirus. Subsequently, samples positive for rhinovirus and enterovirus were routinely sequenced for phylogenetic analysis. Furthermore, an additional method was used to detect EV-D68 specifically. Results During the first three quarters of the year 2014, 1896 respiratory samples were analyzed; 39 (2%) of them tested positive for enterovirus. Eighteen samples tested positive for EV-D68, obtained from 16 different patients admitted to our hospital. Eleven were children below the age of 18, of whom five children needed intensive care treatment. The remaining five samples were from adults, who all had an underlying disease; three were transplant patients (heart, lung and renal transplantation), the other two had an underlying lung condition (COPD, asthma). Phylogenetic analysis showed a close relationship with the strains circulating currently in the USA, all belonging to the known EV-D68 genetic subtypes. Conclusions We observed an increase of EV-D68 infections in our population, both in children as well as in adult. In 2014 there have been 16 cases so far, compared to none in 2011 and 2013 and a single case in 2012. Phylogenetic analysis identified two similar clusters as shown in the USA and Canada.


title: Effective Treatment of Respiratory Alphaherpesvirus Infection Using RNA Interference

text: BACKGROUND: Equine herpesvirus type 1 (EHV-1), a member of the Alphaherpesvirinae, is spread via nasal secretions and causes respiratory disease, neurological disorders and abortions. The virus is a significant equine pathogen, but current EHV-1 vaccines are only partially protective and effective metaphylactic and therapeutic agents are not available. Small interfering RNAs (siRNA's), delivered intranasally, could prove a valuable alternative for infection control. siRNA's against two essential EHV-1 genes, encoding the viral helicase (Ori) and glycoprotein B, were evaluated for their potential to decrease EHV-1 infection in a mouse model. METHODOLOGY/PRINCIPAL FNDINGS: siRNA therapy in vitro significantly reduced virus production and plaque size. Viral titers were reduced 80-fold with 37.5 pmol of a single siRNA or with as little as 6.25 pmol of each siRNA when used in combination. siRNA therapy in vivo significantly reduced viral replication and clinical signs. Intranasal treatment did not require a transport vehicle and proved effective when given up to 12 h before or after infection. CONCLUSIONS/SIGNIFICANCE: siRNA treatment has potential for both prevention and early treatment of EHV-1 infections.


title: Antiviral activity of an aqueous extract derived from Aloe arborescens Mill. against a broad panel of viruses causing infections of the upper respiratory tract

text: Abstract Background A number of antiviral therapies have evolved that may be effectively administered to treat respiratory viral diseases. But these therapies are very often of limited efficacy or have severe side effects. Therefore there is great interest in developing new efficacious and safe antiviral compounds e.g. based on the identification of compounds of herbal origin. Hypothesis Since an aqueous extract of Aloe arborescens Mill. shows antiviral activity against viruses causing infections of the upper respiratory tract in vitro we hypothesised that a product containing it such as Biaron C® could have an antiviral activity too. Study design Antiviral activity of Bioaron C®, an herbal medicinal product consisting of an aqueous extract of Aloe arborescens Mill., Vitamin C, and Aronia melanocarpa Elliot. succus, added as an excipient, was tested in vitro against a broad panel of viruses involved in upper respiratory tract infections. Methods These studies included human adenovirus and several RNA viruses and were performed either with plaque reduction assays or with tests for the detection of a virus-caused cytopathic effect. Results Our studies demonstrated an impressive activity of Bioaron C® against members of the orthomyxoviridae – influenza A and influenza B viruses. Replication of both analysed influenza A virus strains – H1N1 and H3N2 – as well as replication of two analysed influenza B viruses – strains Yamagatal and Beiying – was significantly reduced after addition of Bioaron C® to the infected cell cultures. In contrast antiviral activity of Bioaron C® against other RNA viruses showed a heterogeneous pattern. Bioaron C® inhibited the replication of human rhinovirus and coxsackievirus, both viruses belonging to the family of picornaviridae and both representing non-enveloped RNA viruses. In vitro infections with respiratory syncytial virus and parainfluenza virus, both belonging to the paramyxoviridae, were only poorly blocked by the test substance. No antiviral activity of Bioaron C® was detected against adenovirus – a non-enveloped DNA virus. Conclusions These results represent the first proof of a selective antiviral activity of Bioaron C® against influenza viruses and create basis for further analyses of type and molecular mechanisms of the antiviral activity of this herbal medicine.


title: Nonparametric methods for the analysis of single-color pathogen microarrays

text: BACKGROUND: The analysis of oligonucleotide microarray data in pathogen surveillance and discovery is a challenging task. Target template concentration, nucleic acid integrity, and host nucleic acid composition can each have a profound effect on signal distribution. Exploratory analysis of fluorescent signal distribution in clinical samples has revealed deviations from normality, suggesting that distribution-free approaches should be applied. RESULTS: Positive predictive value and false positive rates were examined to assess the utility of three well-established nonparametric methods for the analysis of viral array hybridization data: (1) Mann-Whitney U, (2) the Spearman correlation coefficient and (3) the chi-square test. Of the three tests, the chi-square proved most useful. CONCLUSIONS: The acceptance of microarray use for routine clinical diagnostics will require that the technology be accompanied by simple yet reliable analytic methods. We report that our implementation of the chi-square test yielded a combination of low false positive rates and a high degree of predictive accuracy.


title: Longitudinal survey of two serotine bat (Eptesicus serotinus) maternity colonies exposed to EBLV-1 (European Bat Lyssavirus type 1): Assessment of survival and serological status variations using capture-recapture models

text: This study describes two longitudinal serological surveys of European Bat Lyssavirus type 1 (EBLV-1) antibodies in serotine bat (Eptesicus serotinus) maternity colonies located in the North-East of France. This species is currently considered as the main EBLV-1 reservoir. Multievent capture-recapture models were used to determine the factors influencing bat rabies transmission as this method accounts for imperfect detection and uncertainty in disease states. Considering the period of study, analyses revealed that survival and recapture probabilities were not affected by the serological status of individuals, confirming the capacity of bats to be exposed to lyssaviruses without dying. Five bats have been found with EBLV-1 RNA in the saliva at the start of the study, suggesting they were caught during virus excretion period. Among these bats, one was interestingly recaptured one year later and harbored a seropositive status. Along the survey, some others bats have been observed to both seroconvert (i.e. move from a negative to a positive serological status) and serorevert (i.e. move from a positive to a negative serological status). Peak of seroprevalence reached 34% and 70% in site A and B respectively. On one of the 2 sites, global decrease of seroprevalence was observed all along the study period nuanced by oscillation intervals of approximately 2–3 years supporting the oscillation infection dynamics hypothesized during a previous EBLV-1 study in a Myotis myotis colony. Seroprevalence were affected by significantly higher seroprevalence in summer than in spring. The maximum time observed between successive positive serological statuses of a bat demonstrated the potential persistence of neutralizing antibodies for at least 4 years. At last, EBLV-1 serological status transitions have been shown driven by age category with higher seroreversion frequencies in adults than in juvenile. Juveniles and female adults seemed indeed acting as distinct drivers of the rabies virus dynamics, hypothesis have been addressed but their exact role in the EBLV-1 transmission still need to be specified.


Corrigendum to “Kinetics and pattern of viral excretion in biological specimens of two MERS-CoV cases’’ [J. Clin. Virol. 61 (2014) 275–278]


title: Communication between S1N330 and a Region in S2 of Murine Coronavirus Spike Protein Is Important for Virus Entry into Cells Expressing CEACAM1b Receptor

text: Abstract The soluble receptor-resistant (srr) mutants, srr7 and srr11, isolated from a murine coronavirus, mouse hepatitis virus (MHV) JHMV, have an amino acid mutation at positions 1114 (Leu to Phe) and 65 (Leu to His), respectively, in the spike (S) protein. These mutants failed to efficiently infect BHK cells expressing CEACAM1b (BHK-R2), due to their low entry into this cell line, although they infected cells expressing CEACAM1a (BHK-R1) in a manner similar to that of wild-type (wt) JHMV cl-2 (Matsuyama and Taguchi, Virology 273, 80–89, 2000). Following the repeated passage of these mutants through BHK-R2 cells, viruses were no longer isolated from srr11-infected cells, while two distinct mutants, srr7A and srr7B, were obtained from srr7-infected cells. Srr7A and srr7B grew 2 log10 higher than srr7 and induced fusion in BHK-R2 cells, being similar to wt virus. In addition to the amino acid change at position 1114 that stemmed from parental srr7, srr7A and srr7B had mutations around position 280, corresponding to the third region of the S1N330 receptor-binding site (S1N330-III) common to all MHV strains examined thus far. Srr7A and srr7B S proteins showed high fusogenicity in both BHK-R1 and BHK-R2 cells, like the wt virus, while srr7Aa and srr7Ba S proteins, which had mutations in S1N330-III but not at amino acid 1114, exhibited profoundly reduced fusion activity in these cell lines. These findings suggest that communication between S1N330-III and the amino acid at position 1114 is important for efficient fusion activity in BHK-R2 cells. S1N330-III is a possible region in the S1 involved in viral entry into cells.


title: Quality vaccines for all people(): Report on the 16th annual general meeting of the Developing Countries Vaccine Manufacturers' Network, 05–07th October 2015, Bangkok, Thailand

text: The Developing Countries Vaccine Manufacturers Network (DCVMN) assembled high-profile leaders from global health organisations and vaccine manufactures for its 16th Annual General Meeting to work towards a common goal: providing quality vaccines for all people. Vaccines contribute to a healthy community and robust health system; the Ebola outbreak has raised awareness of the threat and damage one single infectious disease can make, and it is clear that the world was not prepared. However, more research to better understand emerging infectious agents might lead to suitable vaccines which help prevent future outbreaks. DCVMN members presented their progress in developing novel vaccines against Dengue, HPV, Chikungunya, Cholera, cell-based influenza and other vaccines, demonstrating the commitment towards eliminating and eradicating preventable diseases worldwide through global collaboration and technology transfer. The successful introduction of novel Sabin-IPV and Oral Cholera vaccine in China and Korea respectively in 2015 was highlighted. In order to achieve global immunisation, local authorities and community leaders play an important role in the decision-making in vaccine introduction and uptake, based on the ability of vaccines to protect vaccinated people and protect non-vaccinated in the community through herd immunity. Reducing the risk of vaccine shortages can also be achieved by increasing regulatory convergence at regional and international levels. Combatting preventable diseases remains challenging, and collective efforts for improving multi-centre clinical trials, creating regional vaccine security strategies, fostering developing vaccine markets and procurement, and building trust in vaccines were discussed.


title: Personal Protective Equipment and COVID-19: A Review for Surgeons

text: There is a long history of personal protective equipment (PPE) used by the surgeon to minimize the transmission of various pathogens. In the context of the present coronavirus disease 2019 pandemic there is significant controversy as to what forms of PPE are appropriate or adequate. This review aims to describe the pathogenic mechanism and route of spread of the causative virus, severe acute respiratory syndrome coronavirus, as it pertains to accumulated published data from experienced centers globally. The various forms of PPE that are both available and appropriate are addressed. There are options in the form of eyewear, gloves, masks, respirators, and gowns. The logical and practical utilization of these should be data driven and evolve based on both experience and data. Last, situations specific to surgical populations are addressed. We aim to provide granular collective data that has thus far been published and that can be used as a reference for optimal PPE choices in the perioperative setting for surgical teams.


title: A Genomic Survey of SARS-CoV-2 Reveals Multiple Introductions into Northern California without a Predominant Lineage

text: The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has spread globally, resulting in >300,000 reported cases worldwide as of March 21st, 2020. Here we investigate the genetic diversity and genomic epidemiology of SARS-CoV-2 in Northern California using samples from returning travelers, cruise ship passengers, and cases of community transmission with unclear infection sources. Virus genomes were sampled from 29 patients diagnosed with COVID-19 infection from Feb 3rd through Mar 15th. Phylogenetic analyses revealed at least 8 different SARS-CoV-2 lineages, suggesting multiple independent introductions of the virus into the state. Virus genomes from passengers on two consecutive excursions of the Grand Princess cruise ship clustered with those from an established epidemic in Washington State, including the WA1 genome representing the first reported case in the United States on January 19th. We also detected evidence for presumptive transmission of SARS-CoV-2 lineages from one community to another. These findings suggest that cryptic transmission of SARS-CoV-2 in Northern California to date is characterized by multiple transmission chains that originate via distinct introductions from international and interstate travel, rather than widespread community transmission of a single predominant lineage. Rapid testing and contact tracing, social distancing, and travel restrictions are measures that will help to slow SARS-CoV-2 spread in California and other regions of the USA.


title: Nutraceuticals An Alternative Strategy for the Use of Antimicrobials

text: Livestock industries strive to improve the health of their animals and, in the future, they are going to be required to do this with a continued reduction in antimicrobial use. Nutraceuticals represent a group of compounds that may help fill that void because they exert some health benefits when supplemented to livestock. This review is focused on the mechanisms of action, specifically related to the immune responses and health of ruminants. The nutraceutical classes discussed include probiotics, prebiotics, phytonutrients (essential oils and spices), and polyunsaturated fatty acids.


title: Secondary Photoreceptor Degenerations*

text: Secondary photoreceptor degenerations can be partially distinguished from primary photoreceptor degenerations based upon whether or not correction of the defect in the photoreceptors themselves would be sufficient to arrest photoreceptor death. The distinction is by no means perfect, since there can be genetic mutations that affect directly the survival of photoreceptors as well as the survival of adjacent retinal or retinal pigment epithelium cells that could secondarily be critical for photoreceptor survival. As we attempt to distinguish intrinsic and extrinsic causes of both primary and secondary photoreceptor degenerations, it is increasingly clear that complex interactions and mechanisms can be involved.


Traditional chinese medicine and COVID-19: should emergency practitioners use it?


title: Structural insights of a self-assembling 9-residue peptide from the C-terminal tail of the SARS corona virus E-protein in DPC and SDS micelles: A combined high and low resolution spectroscopic study

text: In recent years, several studies based on the interaction of self-assembling short peptides derived from viroporins with model membranes, have improved our understanding of the molecular mechanism of corona virus (CoV) infection under physiological conditions. In this study, we have characterized the mechanism of membrane interaction of a short, 9-residue peptide TK9 (T(55)VYVYSRVK(63)) that had been derived from the carboxyl terminal of the Severe Acute Respiratory Syndrome (SARS) corona virus (SARS CoV) envelope (E) protein. The peptide has been studied for its physical changes in the presence of both zwitterionic DPC and negatively charged SDS model membrane micelles, respectively, with the help of a battery of biophysical techniques including two-dimensional solution state NMR spectroscopy. Interestingly, in both micellar environments, TK9 adopted an alpha helical conformation; however, the helical propensities were much higher in the case of DPC compared to those of SDS micelle, suggesting that TK9 has more specificity towards eukaryotic cell membrane than the bacterial cell membrane. The orientation of the peptide TK9 also varies in the different micellar environments. The peptide's affinity was further manifested by its pronounced membrane disruption ability towards the mammalian compared to the bacterial membrane mimic. Collectively, the in-depth structural information on the interaction of TK9 with different membrane environments explains the host specificity and membrane orientation owing to subsequent membrane disruption implicated in the viral pathogenesis.


title: Identification of a novel recombinant virulent avian infectious bronchitis virus

text: Abstract The emergence of new infectious bronchitis virus (IBV) variants is often disastrous in the poultry industry. In this study, an IBV, CK/CH/2010/JT-1, was isolated from an H120- and 4/91-IBV-vaccinated flock in China. Antisera against vaccine strains H120 and 4/91 could not provide effective protection against CK/CH/2010/JT-1 in virus neutralization assays. CK/CH/2010/JT-1 could cause 43.75% mortality with respiratory and severe renal lesions in inoculated chickens. Phylogenetic analysis of the S1 gene showed that CK/CH/2010/JT-1 and 31 other isolates could be grouped as a new genotypic cluster. Recombination analysis revealed that three recombination events could be found in the genome of CK/CH/2010/JT-1 at positions 24709-365, 17160-19811 and 21136-21770. Whole-genome sequence analysis showed that CK/CH/2010/JT-1 originated from multiple template switches among QX-like, CK/CH/LSC/99I-, tl/CH/LDT3/03- and 4/91-type IBVs. All of these data demonstrated that CK/CH/2010/JT-1 is a new recombinant genotype IBV with high virulence. Our findings suggest that the surveillance of new genotype strains of IBV is very important for developing more effective anti-IBV strategies.


title: Potential airborne pathogen transmission in a hospital with and without surge control ventilation system modifications

text: Abstract To better understand the transport of airborne particulate matter (PM) in hospital environments when surge control strategies are implemented, tests were conducted in a recently decommissioned hospital during a one-week period. An aerosol was released within a patient room and concentrations measured in the room and hallway with and without surge control ventilation system modifications. The average hallway protection efficiencies were high (>98%) both for the baseline ventilation configuration and when the ventilation system was modified for whole floor negative pressure, indicating very little PM reached the hallway. During entry/exit events through the patient room door into the hallway, the average minimum hallway protection efficiencies were lower during the modified ventilation operation (93–94%) than for the baseline operation (98–99%). These lower hallway protection efficiencies may be explained by the 52% reduction in the outdoor air ventilation being supplied to the hallway during the modified operation mode. This suggests that patient room doors should remain closed to control PM movement into the hallway. In addition, if there is concern about airborne infection transmission, an anteroom may be used to further reduce the transport of particles from the patient rooms to the hallways of the ward.


title: Kidney transplantation with pre‐symptomatic COVID‐19 positive surgeon

text: In Italy the Coronavirus Disease 2019 (COVID‐19) outbreak caused by SARS‐CoV‐2 is testing the national health system and the intensive care unit are at the limits of their capacity. Severe travel limitation and containment at home were applied, such as in the Chinese experience and isolation of the diseased patients to control the exponential trend of the infection spread.


title: Transcriptional profiles of PBMCs from pigs infected with three genetically diverse porcine reproductive and respiratory syndrome virus strains

text: Porcine reproductive and respiratory syndrome virus is the cause of reproductive failure in sows and respiratory disease in young pigs, which has been considered as one of the most costly diseases to the worldwide pig industry for almost 30 years. This study used microarray-based transcriptomic analysis of PBMCs from experimentally infected pigs to explore the patterns of immune dysregulation after infection with two East European PRRSV strains from subtype 2 (BOR and ILI) in comparison to a Danish subtype 1 strain (DAN). Transcriptional profiles were determined at day 7 post infection in three tested groups of pigs and analysed in comparison with the expression profile of control group. Microarray analysis revealed differential regulation (> 1.5-fold change) of 4253 and 7335 genes in groups infected with BOR and ILI strains, respectively, and of 12518 genes in pigs infected with Danish strain. Subtype 2 PRRSV strains showed greater induction of many genes, especially those involved in innate immunity, such as interferon stimulated antiviral genes and inflammatory markers. Functional analysis of the microarray data revealed a significant up-regulation of genes involved in processes such as acute phase response, granulocyte and agranulocyte adhesion and diapedesis, as well as down-regulation of genes enrolled in pathways engaged in protein synthesis, cell division, as well as B and T cell signaling. This study provided an insight into the host response to three different PRRSV strains at a molecular level and demonstrated variability between strains of different pathogenicity level. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11033-018-4204-x) contains supplementary material, which is available to authorized users.


title: The envelope protein of severe acute respiratory syndrome coronavirus interacts with the non-structural protein 3 and is ubiquitinated

text: Abstract To analyze the proteins interacting with the severe acute respiratory syndrome coronavirus (SARS-CoV) envelope (E) protein, a SARS-CoV was engineered including two tags associated to the E protein. Using this virus, complexes of SARS-CoV E and other proteins were purified using a tandem affinity purification system. Several viral and cell proteins including spike, membrane, non-structural protein 3 (nsp3), dynein heavy chain, fatty acid synthase and transmembrane protein 43 bound E protein. In the present work, we focused on the binding of E protein to nsp3 in infected cells and cell-free systems. This interaction was mediated by the N-terminal acidic domain of nsp3. Moreover, nsp3 and E protein colocalized during the infection. It was shown that E protein was ubiquitinated in vitro and in cell culture, suggesting that the interaction between nsp3 and E protein may play a role in the E protein ubiquitination status and therefore on its turnover.


title: The Global One Health Paradigm: Challenges and Opportunities for Tackling Infectious Diseases at the Human, Animal, and Environment Interface in Low-Resource Settings

text: Zoonotic infectious diseases have been an important concern to humankind for more than 10,000 years. Today, approximately 75% of newly emerging infectious diseases (EIDs) are zoonoses that result from various anthropogenic, genetic, ecologic, socioeconomic, and climatic factors. These interrelated driving forces make it difficult to predict and to prevent zoonotic EIDs. Although significant improvements in environmental and medical surveillance, clinical diagnostic methods, and medical practices have been achieved in the recent years, zoonotic EIDs remain a major global concern, and such threats are expanding, especially in less developed regions. The current Ebola epidemic in West Africa is an extreme stark reminder of the role animal reservoirs play in public health and reinforces the urgent need for globally operationalizing a One Health approach. The complex nature of zoonotic diseases and the limited resources in developing countries are a reminder that the need for implementation of Global One Health in low-resource settings is crucial. The Veterinary Public Health and Biotechnology (VPH-Biotec) Global Consortium launched the International Congress on Pathogens at the Human-Animal Interface (ICOPHAI) in order to address important challenges and needs for capacity building. The inaugural ICOPHAI (Addis Ababa, Ethiopia, 2011) and the second congress (Porto de Galinhas, Brazil, 2013) were unique opportunities to share and discuss issues related to zoonotic infectious diseases worldwide. In addition to strong scientific reports in eight thematic areas that necessitate One Health implementation, the congress identified four key capacity-building needs: (1) development of adequate science-based risk management policies, (2) skilled-personnel capacity building, (3) accredited veterinary and public health diagnostic laboratories with a shared database, and (4) improved use of existing natural resources and implementation. The aim of this review is to highlight advances in key zoonotic disease areas and the One Health capacity needs.


title: Genetic diversity and phylogenetic analysis of newly discovered bat astroviruses in Korea

text: Bats have been identified as a natural reservoir for several potentially zoonotic viruses. Recently, astroviruses have been reported in bats in many countries, but not Korea. We collected 363 bat samples from thirteen species at twenty-nine sites in Korea across 2016 and tested them for astrovirus. The detection of the RNA-dependent RNA polymerase (RdRp) gene in bat astroviruses was confirmed in thirty-four bats across four bat species in Korea: twenty-five from Miniopterus fuliginosusi, one from Myotis macrodactylus, four from M. petax, and four from Rhinolophus ferrumequinum. The highest detection rates for astrovirus were found in Sunchang (61.5%, 8/13 bats), and in the samples collected in April (63.2%, 12/19 bats). The amino acid identity of astroviral sequences identified from bat samples was ≥ 46.6%. More specifically, the amino acid identity within multiple clones from individual bats was ≥ 50.8%. Additionally, the phylogenetic topology between astroviruses from different bat families showed a close relationship. Furthermore, phylogenetic analysis of the partial ORF2 sequence of bat astroviruses was found to have a maximum similarity of 73.3–74.8% with available bat astrovirus sequences. These results indicate potential multiple-infection by several bat astrovirus species in individual bats, or hyperpolymorphism in the astrovirus strains, as well as the transmission of astroviruses across bat families; furthermore, our phylogenetic analysis of the partial ORF2 implied that a novel astrovirus may exist. However, the wide diversity of astroviral sequences appeared to have no significant correlation with bat species or the spatiotemporal distribution of Korean bat astroviruses.


title: A worthy introduction For the book see http://www.amazon.co.uk/Infectious-Disease-Short-Introduction-Introductions/dp/0199688931

text: Unknown


Index to volume 43, January–June 2004


title: Unemployment in the time of COVID-19: A research agenda

text: Abstract This essay represents the collective vision of a group of scholars in vocational psychology who have sought to develop a research agenda in response to the massive global unemployment crisis that has been evoked by the COVID-19 pandemic. The research agenda includes exploring how this unemployment crisis may differ from previous unemployment periods; examining the nature of the grief evoked by the parallel loss of work and loss of life; recognizing and addressing the privilege of scholars; examining the inequality that underlies the disproportionate impact of the crisis on poor and working class communities; developing a framework for evidence-based interventions for unemployed individuals; and examining the work-family interface and unemployment among youth.


Presence of ON1 and BA HRSV-genotypes in Paraguay, 2010–2013


Preventing the Emergence of Corona Virus Disease 2019 Outbreak in Mass Gatherings: Appeal to Public Health Authorities


title: Topical pharmacotherapy for allergic rhinitis: Nedocromil

text: Abstract Nedocromil sodium is a mast-cell stabilizer that prevents or ablates both the acute and late phases of the allergic response. It is an antiinflammatory agent that is not a steroid. It is more potent than the currently available mastcell stabilizer, cromolyn, and maintenance therapy may be possible at less frequent intervals than the initially recommended regimen of 4 times daily. Nedocromil for pulmonary administration is currently available. The nasal form has undergone clinical trials but has not yet been released in the United States.


Characteristics of COVID-19 pandemic and public health consequences


title: Receptive Music Therapy to reduce stress and improve wellbeing in Italian Clinical Staff involved in COVID-19 Pandemic: a preliminary study

text: The influence of music therapy (MT) as a support intervention to reduce stress and improve wellbeing in Clinical Staff (CS) working with COVID-19 patients was evaluated. Participants were enrolled as a result of spontaneous agreement (n = 34) and were given remote receptive MT intervention over a 5-week period. Their levels of tiredness, sadness, fear and worry were measured with MTC-Q1 before and after MT intervention. An immediate significant variation in the CS emotional status was observed. The results seem to confirm that in an emergency situation, it is possible to put in place a remote MT support intervention for CS exposed to highly stressful situations.


title: Appraising the risk level of physicochemical and bacteriological twin contaminants of water resources in part of the western Niger Delta region

text: This study was carried out to assess the physicochemical and bacteriological contaminants of surface, shallow well and municipal borehole waters in part of the western Niger Delta as a way of safeguarding public health against waterborne diseases. A total of 72 water samples collected from the study area were analysed and their results show that the pH average value ranges from 6.2 in the dry to 8.5 in the rainy seasons for surface water, 6.6 and 8.3 for shallow well water and 6.5 to 8.4 for borehole water. The turbidity in surface water varies from 8.1 to 26.2 Formazin Attenuation Unit (FAU), 0.3 to 2.9 FAU in shallow well water and 0.4 to 4.8 FAU in borehole water. Electrical conductivity (EC) value varies from 1010 to 1840 μs/cm for surface water, 201 to 950 μs/cm for shallow well water and 670 to 1650 μs/cm for borehole water. Total dissolved solids range from 0.1 to 2.6 mg/l in surface water, 0.2 to 4.1 mg/l in shallow well water and 0.3 to 4.4 mg/l in borehole water. The value of the total hardness ranges from 44 to 120 mg in surface water, 46 to 96 mg in shallow well water and 70 to 130 mg in borehole water. The nitrate value ranges from 1.1 to 10.6 mg in surface water, 3.0 to 8.4 mg in shallow well water and 3.7 to 9.6 mg in borehole water. The value of sulphate content varies from 4.6 to 38.5 mg in surface water, 6.2 to 34.8 mg in shallow well water and 5.7 to 55.7 mg in borehole water. The value of phosphate concentrations in surface water varies from 1.0 to 9.0 mg, 0.7 to 3.4 mg in shallow well water and 1.0 to 4.7 mg in borehole water. The bacteriological analysis using the membrane filtration technique revealed the presence of faecal bacteria and total coliform counts. The presence of the analysed twin contaminants in the studied water resources reduced their water quality. The physicochemical and bacteriological data were subjected to statistical and correlation tests. It was concluded that their concentration levels were independent of intra-seasonal changes. The likely natural and artificial sources of contaminants are run-offs from fertilized lands, septic tanks, industrial discharges, sewage and waste disposal, algae blooms and erosion from natural deposits. The inherent risk is water-related diseases such as waterborne diseases, water-washed diseases, water-based diseases and diseases transmitted by water-related insect vectors. Water resources should be protected through proper sanitation systems, limiting of up-stream discharges, maintenance of wellheads, boiling and municipal water treatment plants. Educational advice should be given to the inhabitants on the dangers posed by continuous drinking of contaminated water. These measures will prevent disease outbreak and public health burden in the area.


title: Development of nasal, fecal and serum isotype-specific antibodies in calves challenged with bovine coronavirus or rotavirus

text: Abstract Unsuckled specific pathogen free calves were inoculated at 3–4 weeks of age, either intranasally (IN) or orally (O) with bovine coronavirus or O plus IN (O/IN) or O with bovine rotavirus. Shedding of virus in nasal or fecal samples, and virus-infected nasal epithelial cells were detected using immunofluorescent staining (IF), ELISA or immune electron microscopy (IEM). Isotype-specific antibody titers in sera, nasal and fecal samples were determined by ELISA. Calves inoculated with coronavirus shed virus in feces and virus was detected in nasal epithelial cells. Nasal shedding persisted longer in IN-inoculated calves than in O-inoculated calves and longer than fecal shedding in both IN and O-inoculated calves. Diarrhea occurred in all calves, but there were no signs of respiratory disease. Calves inoculated with rotavirus had similar patterns of diarrhea and fecal shedding, but generally of shorter duration than in coronavirus-inoculated calves. No nasal shedding of rotavirus was detected. Peak IgM antibody responess, in most calves, were detected in fecal and nasal speciments at 7–10 days post-exposure (DPE), preceeding peak IgA responses which occurred at 10–14 DPE. The nasal antibody responses occurred in all virus-inoculated calves even in the absence of nasal shedding of virus in rotavirus-inoculated calves. Calves inoculated with coronavirus had higher titers of IgM and IgA antibodies in fecal and nasal samples than rotavirus-inoculated calves. In most inoculated calves, maximal titers of IgM or IgA antibodies correlated with the cessation of fecal or nasal virus shedding. A similar sequence of appearance of IgM and IgA antibodies occurred in serum, but IgA antibodies persisted for a shorter period than in fecal or nasal samples. Serum IgG1 antibody responses generally preceeded IgG2 responses and were predominant in most calves after 14–21 DPE.


title: Pelargonium sidoides extract EPs 7630: a review of its clinical efficacy and safety for treating acute respiratory tract infections in children

text: BACKGROUND: In numerous randomized controlled trials (RCTs) and systematic reviews such as those published by the Cochrane Collaboration, Pelargonium sidoides extract EPs(®) 7630 was shown to be effective in acute respiratory tract infections (aRTI) in all investigated age-groups. This narrative review focuses on recently published results from RCTs investigating the clinical efficacy and safety of EPs 7630 in children and adolescents with different manifestations of aRTI, in order to present a broader overview and to provide an update on the state of knowledge regarding the use of EPs 7630 in this age-group. METHODS: The Cochrane review on P. sidoides extract for aRTI published by the Cochrane Collaboration was searched for cited RCTs with EPs 7630 in children and adolescents suffering from aRTI. A PubMed and SCOPUS literature search was performed for publications issued before June 13, 2017 (search terms: children, Pelargonium sidoides, EPs 7630, respiratory). Reference lists of publications found were searched for relevant citations. RESULTS: Eight RCTs investigating the application of EPs 7630 in acute bronchitis, acute tonsil-lopharyngitis, and aRTI in the context of chronic preconditions were identified. Results showed a statistically significant improvement of aRTI symptom severity for EPs 7630 as compared to controls. The investigation of EPs 7630 in asthmatic children and adolescents with aRTI demonstrated a significant symptom-alleviating effect and a possibly associated reduction of asthma attacks. In immunocompromised children with acute upper RTI, an alleviating effect of EPs 7630 was shown. All RCTs reviewed reported good safety and tolerability of EPs 7630. CONCLUSION: The P. sidoides extract EPs 7630 is effective and safe for those of pediatric age and may be regarded as an alternative option for the management of aRTI.


title: Successful recovery of MERS CoV pneumonia in a patient with acquired immunodeficiency syndrome: A case report

text: Abstract Middle East Respiratory Syndrome Coronavirus (MERS CoV) may cause severe pneumonia with significant morbidity and mortality, particularly in patients with multiple comorbid condition. MERS CoV pneumonia has not been previously reported in patients with Human Immunodeficiency Virus (HIV). Herein, we report a case of MERS CoV pneumonia with a successful outcome in a patient recently diagnosed with HIV.


title: Duration of wheezy episodes in early childhood is independent of the microbial trigger

text: Background Wheezy episodes in young children are often triggered by viral and bacterial respiratory tract infections, but there is little evidence supporting the hypothesis that symptom duration depends on the specific microbial trigger. Objective We sought to investigate whether the duration of wheezy episodes in young children depends on the microbial trigger. Methods Two hundred eighty-three children from the Copenhagen Prospective Study on Asthma in Childhood2000 at-risk birth cohort were prospectively examined for common airway pathogenic bacteria and viruses during acute wheezy episodes in the first 3 years of life. Findings were related to symptomatic duration of episodes, as monitored in daily diary cards from birth. Results Eight hundred thirty-seven samples were investigated for viruses, bacteria, or both. Both viruses and bacteria were identified in 55% of episodes, bacteria were identified exclusively in 31% of episodes, and viruses were identified exclusively in 10% of episodes. The median duration of acute symptoms was 9 days (interquartile range, 5-16 days), and duration was independent of bacterial or viral species. Conclusions The duration of wheezy episodes was independent of pathogenic airway bacterial or viral species. This suggests that symptom burden from infections is dependent on other factors, such as environmental exposures or host factors. The common term viral wheeze seems inappropriate in view of the finding of pathogenic bacteria in 86% of wheezy episodes.


title: A novel clinical set‐up for examining healthy dermatology outpatients during the COVID‐19 pandemic

text: The pandemic of COVID-19 has made social distancing necessary as a result, daily outpatient departments (OPD) are at a standstill due to rule imposed by many governing bodies to close all non-essential OPDs.


title: Development of an indirect ELISA, blocking ELISA, fluorescent microsphere immunoassay and fluorescent focus neutralization assay for serologic evaluation of exposure to North American strains of Porcine Epidemic Diarrhea Virus

text: BACKGROUND: Recent, severe outbreaks of porcine epidemic diarrhea virus (PEDV) in Asia and North America highlight the need for well-validated diagnostic tests for the identification of PEDV infected animals and evaluation of their immune status to this virus. PEDV was first detected in the U.S. in May 2013 and spread rapidly across the country. Some serological assays for PEDV have been previously described, but few were readily available in the U.S. Several U.S. laboratories quickly developed indirect fluorescent antibody (IFA) assays for the detection of antibodies to PEDV in swine serum, indicating prior exposure. However, the IFA has several disadvantages, including low throughput and relatively subjective interpretation. Different serologic test formats have advantages and disadvantages, depending on the questions being asked, so a full repertoire of tests is useful. Therefore, the objective of this study was to develop and validate multiple improved serological assays for PEDV, including an indirect ELISA (iELISA); a highly specific monoclonal antibody-based blocking ELISA (bELISA); fluorescent microsphere immunoassays (FMIA) that can be multiplexed to monitor exposure to multiple antigens and pathogens simultaneously; and a fluorescent focus neutralization assay (FFN) to measure functional virus neutralizing antibodies. RESULTS: A recombinant North American nucleoprotein (NP) based iELISA was developed and validated along with a bELISA using newly developed PEDV-NP specific biotinylated monoclonal antibodies (mAbs) and an FMIA using magnetic beads coupled with expressed NA PEDV-NP. Receiver operating characteristic (ROC) analysis was performed using swine serum samples (iELISA n = 1486, bELISA n = 1186, FMIA n = 1420). The ROC analysis for the FMIA showed estimated sensitivity and specificity of 98.2 and 99.2 %, respectively. The iELISA and bELISA showed a sensitivity and specificity of 97.9 and 97.6 %; and 98.2 and 98.9 %, respectively. Inter-rater (kappa) agreement was calculated to be 0.941 between iELISA and IFA, 0.945 between bELISA and IFA and 0.932 between FMIA and IFA. Similar comparative kappa values were observed between the iELISA, bELISA and FMIA, which demonstrated a significant level of testing agreement among the three assays. No cross-reactivity with the closely related coronaviruses, transmissible gastroenteritis virus (TGEV) or porcine respiratory coronavirus (PRCV) was noted with these assays. All three assays detected seroconversion of naïve animals within 6–9 days post exposure. The FFN assay allows relative quantitation of functional neutralizing antibodies in serum, milk or colostrum samples. CONCLUSION: Well-validated iELISA, bELISA and FMIA assays for the detection of PEDV antibodies were developed and showed good correlation with IFA and each other. Each assay format has advantages that dictate how they will be used in the field. Newly developed mAbs to the PEDV-NP were used in the bELISA and for expediting FFN testing in the detection and quantitation of neutralizing antibodies. In addition, these PEDV mAbs are useful for immunohistochemistry, fluorescent antibody staining and other antigen-based tests. Measurement of neutralizing antibody responses using the FFN assay may provide a valuable tool for assessment of vaccine candidates or protective immunity.


title: Pathogenic mechanisms implicated in the intravascular coagulation in the lungs of BVDV-infected calves challenged with BHV-1

text: Resistance to respiratory disease in cattle requires host defense mechanisms that protect against pathogens which have evolved sophisticated strategies to evade them, including an altered function of pulmonary macrophages (MΦs) or the induction of inflammatory responses that cause lung injury and sepsis. The aim of this study was to clarify the mechanisms responsible for vascular changes occurring in the lungs of calves infected with bovine viral diarrhea virus (BVDV) and challenged later with bovine herpesvirus type 1 (BHV-1), evaluating the role of MΦs in the development of pathological lesions in this organ. For this purpose, pulmonary lesions were compared between co-infected calves and healthy animals inoculated only with BHV-1 through immunohistochemical (MAC387, TNFα, IL-1α, iNOS, COX-2 and Factor-VIII) and ultrastructural studies. Both groups of calves presented important vascular alterations produced by fibrin microthrombi and platelet aggregations within the blood vessels. These findings were earlier and more severe in the co-infected group, indicating that the concomitance of BVDV and BHV-1 in the lungs disrupts the pulmonary homeostasis by facilitating the establishment of an inflammatory and procoagulant environment modulated by inflammatory mediators released by pulmonary MΦs. In this regard, the co-infected calves, in spite of presenting a greater number of IMΦs than single-infected group, show a significant decrease in iNOS expression coinciding with the presence of more coagulation lesions. Moreover, animals pre-inoculated with BVDV displayed an alteration in the response of pro-inflammatory cytokines (TNFα and IL-1), which play a key role in activating the immune response, as well as in the local cell-mediated response.


title: SARS‐CoV‐2 environmental contamination associated with persistently infected COVID‐19 patients

text: BACKGROUND: Severe COVID‐19 patients typically test positive for SARS‐CoV‐2 RNA for extended periods of time, even after recovery from severe disease. Due to the timeframe involved, these patients may have developed humoral immunity to SARS‐CoV‐2 while still testing positive for viral RNA in swabs. Data are lacking on exposure risks in these situations. Here, we studied SARS‐CoV‐2 environmental contamination in an ICU and an isolation ward caring for such COVID‐19 patients. METHODS: We collected air and surface samples in a hospital caring for critical and severe COVID‐19 cases from common areas and areas proximal to patients. RESULTS: Of the 218 ICU samples, an air sample contained SARS‐CoV‐2 RNA. Of the 182 isolation ward samples, nine contained SARS‐CoV‐2 RNA. These were collected from a facemask, the floor, mobile phones, and the air in the patient room and bathroom. Serum antibodies against SARS‐CoV‐2 were detected in these patients at the beginning of the study. CONCLUSIONS: While there is a perception of increased risk in the ICU, our study demonstrates that isolation wards may pose greater risks to healthcare workers and exposure risks remain with clinically improved patients, weeks after their initial diagnoses. As these patients had serum antibodies, further studies may be warranted to study the utility of serum antibodies as a surrogate of viral clearance in allowing people to return to work. We recommend continued vigilance even with patients who appear to have recovered from COVID‐19.


title: Effects of lactation and pregnancy on gene expression of endometrium of Holstein cows at day 17 of the estrous cycle or pregnancy

text: Abstract Objectives were to determine effects of lactation and pregnancy on endometrial gene expression on d 17 of the estrous cycle and pregnancy. Heifers (n=33) were assigned randomly after parturition to lactating (L, n=17) or nonlactating (NL, n=16) groups. Cows were subjected to an ovulation synchronization program for a timed artificial insemination (TAI); 10 cows in L and 12 in NL were inseminated. Slaughter occurred 17 d after the day equivalent to TAI, and intercaruncular endometrial tissues were collected. Gene expression was determined by DNA microarray analysis for pregnant (L, n=8; NL, n=6) and noninseminated cyclic (L, n=7; NL, n=4) cows. Differentially expressed genes were selected with a P-value <0.01 and absolute expression >40. In addition, a fold effect >1.5 was used as a criterion for genes affected by pregnancy. In total, 210 genes were differentially regulated by lactation (136 downregulated and 74 upregulated), and 702 genes were differentially regulated by pregnancy (407 downregulated and 295 upregulated). The interaction effect of pregnancy and lactation affected 61 genes. Genes up- and downregulated in pregnant cows were associated with several gene ontology terms, such as defense response and interferon regulatory factor, cell adhesion, and extracellular matrix. The gene ontology analyses of up- and downregulated genes of lactating cows revealed terms related to immunoglobulin-like fold, immune response, COMM domain, and non-membrane-bounded organelle. Several genes upregulated by lactation, such as IGHG1, IGLL1, IGK, and TRD, were related to immune function, particularly for B cells and γδ T cells. Developmental genes related to limb and neural development and glucose homeostasis (e.g., DKK1, RELN, PDK4) were downregulated by lactation, whereas an interaction was also detected for RELN. The stated genes associated with immune function and developmental genes expressed in the endometrium affected by lactational state are possible candidate genes for interventions to improve fertility of lactating dairy cows.


title: Purine analogs as phosphatidylinositol 4-kinase IIIβ inhibitors

text: Abstract We report on an extensive structure–activity relationship study of novel PI4K IIIβ inhibitors. The purine derivative of the potent screening hit T-00127-HEV1 has served as a suitable starting point for a thorough investigation of positions 8 and 2. While position 8 of the purine scaffold can only bear a small substituent to maintain the inhibitory activity, position 2 is opened for extensive modification and can accommodate even substituted phenyl rings without the loss of PI4K IIIβ inhibitory activity. These empirical observations nicely correlate with the results of our docking study, which suggests that position 2 directs towards solution and can provide the necessary space for the interaction with remote residues of the enzyme, whereas the cavity around position 8 is strictly limited. The obtained compounds have also been subjected to antiviral screening against a panel of (+)ssRNA viruses.


title: Endocytosis of the receptor-binding domain of SARS-CoV spike protein together with virus receptor ACE2

text: Abstract Cell entry of severe acute respiratory syndrome coronavirus (SARS-CoV) is mediated by the viral spike (S) protein. Amino acids 319–510 on the S protein have been mapped as the receptor-binding domain (RBD), which mediates binding to the SARS-CoV receptor angiotensin converting enzyme 2 (ACE2) on SARS-CoV susceptible cells. In this study, we expressed a fusion protein containing the human codon-optimized RBD of the SARS-CoV spike protein linked to the Fc portion of human IgG1 (named RBD-Fc) in HEK293 cells. The RBD-Fc protein was purified by affinity chromatography. The flow cytometry assay showed that the purified RBD-Fc protein could bind to ACE2. We demonstrated that the RBD spike protein alone could be internalized into SARS-CoV susceptible cells together with ACE2. We also showed that the removal of N-glycans from the RBD spike protein did not abolish this phenomenon. Our discoveries may have some implications for the development of the SARS vaccine.


title: Evaluation of a single-tube fluorogenic RT-PCR assay for detection of bovine respiratory syncytial virus in clinical samples

text: Abstract Bovine respiratory syncytial virus (BRSV) causes severe disease in naïve cattle of all ages and is a common pathogen in the respiratory disease complex of calves. Simplified methods for rapid BRSV diagnosis would encourage sampling during outbreaks and would consequently lead to an extended understanding of the virus. In this study, a BRSV fluorogenic reverse transcription PCR (fRT-PCR) assay, based on TaqMan principle, was developed and evaluated on a large number of clinical samples, representing various cases of natural and experimental BRSV infections. By using a single-step closed-tube format, the turn-around time was shortened drastically and results were obtained with minimal risk for cross-contamination. According to comparative analyses, the detection limit of the fRT-PCR was on the same level as that of a nested PCR and the sensitivity relatively higher than that of a conventional PCR, antigen ELISA (Ag-ELISA) and virus isolation (VI). Interspersed negative control samples, samples from healthy animals and eight symptomatically or genetically related viruses were all negative, confirming a high specificity of the assay. Taken together, the data indicated that the fRT-PCR assay can be applied to routine virus detection in clinical specimens and provides a rapid and valuable tool in BRSV research.


A Disease Around the Corner


title: Adenovirus-mediated expression of CXCL10 in the central nervous system results in T-cell recruitment and limited neuropathology

text: In the present study, the authors evaluated the contributions of the CXC chemokine ligand (CXCL)10 to leukocyte recruitment into the central nervous system (CNS) and disease development. Instillation of a replication-deficient adenovirus that expresses CXCL10 (AdCXCL10) into the CNS of C57BL/6 mice resulted in a rapid (day 3) and prolonged (day 21) infiltration of both CD4(+) and CD8(+) T cells as compared to mice infected with an adenovirus vector containing β-galactosidase (Adβgal). Despite increased T-cell infiltration into the CNS of AdCXCL10-infected mice, production of proinflammatory chemokines normally associated with the recruitment of activated T cells into the CNS was muted and mice developed limited neuropathology. Therefore, these results indicate that T-cell infiltration in the absence of appropriate activation is not sufficient to induce pathology within the CNS and that additional signals other than CXCL10 are required for induction of an immune-mediated neurologic disease.


title: The relevance of allergen exposure to the development of asthma in childhood()()()

text: Sensitization to 1 or more of the common indoor allergens has been consistently associated with asthma among children and young adults (odds ratios for asthma, 3-18). For dust mite and cockroach allergens, there is a dose response relationship between domestic exposure and sensitization. Given that allergen provocation can induce many of the features of asthma, the findings strongly suggest that there is a causal relationship between allergen exposure in the home and asthma. However, it remains unclear at what time the critical exposure occurs (ie, in infancy or later) and what role allergen exposure has played in the increasing prevalence and severity of asthma. Objective evidence of an immune response to allergens is generally not present until after 2 years of age. Viral infections play several different roles in asthma in childhood. In infancy, respiratory syncytial virus infection can induce bronchiolitis and set up recurrent wheezing over the next few years. However, the risk factors for this are maternal smoking and small lungs at birth, rather than allergy. By contrast, the role of rhinovirus in precipitating attacks in children and young adults is strongly associated with allergy. Thus the likely scenario is that allergen exposure over the first few years of life induces sensitization (ie, T(H2) cells and IgE antibodies). Continuing exposure can maintain inflammation in the nose and lungs. However, many other factors contribute to wheezing such that there is no simple relationship between allergen exposure and asthma. Nonetheless, it is clear that the changes that have increased asthma have acted on allergic children. (J Allergy Clin Immunol 2000;105:S503-8.)


title: Explicit non-Markovian susceptible-infected-susceptible mean-field epidemic threshold for Weibull and Gamma infections but Poisson curings

text: Although non-Markovian processes are considerably more complicated to analyze, real-world epidemics are likely non-Markovian, because the infection time is not always exponentially distributed. Here, we present analytic expressions of the epidemic threshold in a Weibull and a Gamma SIS epidemic on any network, where the infection time is Weibull, respectively, Gamma, but the recovery time is exponential. The theory is compared with precise simulations. The mean-field non-Markovian epidemic thresholds, both for a Weibull and Gamma infection time, are physically similar and interpreted via the occurrence time of an infection during a healthy period of each node in the graph. Our theory couples the type of a viral item, specified by a shape parameter of the Weibull or Gamma distribution, to its corresponding network-wide endemic spreading power, which is specified by the mean-field non-Markovian epidemic threshold in any network.


title: Identification of Secreted Proteins Involved in Nonspecific dsRNA-Mediated Lutzomyia longipalpis LL5 Cell Antiviral Response

text: Hematophagous insects transmit infectious diseases. Sand flies are vectors of leishmaniasis, but can also transmit viruses. We have been studying immune responses of Lutzomyia longipalpis, the main vector of visceral leishmaniasis in the Americas. We identified a non-specific antiviral response in L. longipalpis LL5 embryonic cells when treated with non-specific double-stranded RNAs (dsRNAs). This response is reminiscent of interferon response in mammals. We are investigating putative effectors for this antiviral response. Secreted molecules have been implicated in immune responses, including interferon-related responses. We conducted a mass spectrometry analysis of conditioned medium from LL5 cells 24 and 48 h after dsRNA or mock treatment. We identified 304 proteins. At 24 h, 19 proteins had an abundance equal or greater than 2-fold change, while the levels of 17 proteins were reduced when compared to control cells. At the 48 h time point, these numbers were 33 and 71, respectively. The two most abundant secreted peptides at 24 h in the dsRNA-transfected group were phospholipid scramblase, an interferon-inducible protein that mediates antiviral activity, and forskolin-binding protein (FKBP), a member of the immunophilin family, which mediates the effect of immunosuppressive drugs. The transcription profile of most candidates did not follow the pattern of secreted protein abundance.


title: Strengthening community-based initiatives for health emergency management

text: Abstract An analysis of the situation of health emergencies in the Western Pacific Region and how the World Health Organization (WHO) has provided support to member states is presented in the paper. Emergency and Humanitarian Action is one of the youngest programmes of the WHO Regional Office for the Western Pacific. Despite its organizational size and budgetary limitations, it has endeavored to adequately respond to regional needs for preparedness and response. The paper further looks into approaches for strengthening preparedness, collaboration, and action for disasters and how a community-based approach should offer the best preparedness and response alternative for the region. Examples of country efforts are included. Community-based initiatives are taken as integral components of public health efforts for health emergency management. Thus, public health plays a very crucial role in emergencies.


title: Noscapine, a possible drug candidate for attenuation of cytokine release associated with SARS‐CoV‐2

text: Successful treatment of viral infections has proven to be huge challenge for modern medicine with the most effective approach being prior vaccination. The problem with vaccination is the time it takes to develop an effective vaccine, validate its safety and manufacture it in large quantities. Facing Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2), we simply do not have the time to develop the vaccine before thousands of people die. Therefore, any treatment which can decrease the severe symptoms due to lung damage may help attenuate mortality rates. Inactivation of ACE2 during virus fusion into the host cell may be one of the underlying reasons for intense immunological reaction seen in the lung tissue. This overreaction is probably mediated through the bradykinin receptor activation. Noscapine, a medication used for the treatment of cough, has been shown to inhibit bradykinin enhanced cough response in man. As it is already marketed in a number of countries as a cough medicine, even for children, a suitable formulation with all the required licenses is available that can be rapidly utilized in preliminary trials.


title: Three months of informational trends in COVID-19 across New York City

text: In the midst of widespread community transmission of coronavirus disease 2019 (COVID-19) in New York, residents have sought information about COVID-19. We analyzed trends in New York State (NYS) and New York City (NYC) data to quantify the extent of COVID-19-related queries. Data on the number of 311 calls in NYC, Google Trend data on the search term ‘Coronavirus’ and information about trends in COVID-19 cases in NYS and the USA were compiled from multiple sources. There were 1228 994 total calls to 311 between 22 January 2020 and 22 April 2020, with 50 845 calls specific to COVID-19 in the study period. The proportion of 311 calls related to COVID-19 increased over time, while the ‘interest over time’ of the search term ‘Coronavirus’ has exponentially increased since the end of February 2020. It is vital that public health officials provide clear and up-to-date information about protective measures and crucial communications to respond to information-seeking behavior across NYC.


title: Characteristics of venous thromboembolism in COVID-19 patients: a multicenter experience from Northern Italy.

text: OBJECTIVE: The liability of patients affected by novel coronavirus disease (COVID-19) to develop venous thromboembolic events (VTE) is widely acknowledged. However, many particulars of the interactions between the two diseases are still unknown. This study aims to outline the main characteristics of deep venous thrombosis (DVT) and pulmonary embolism (PE) in COVID-19 patients, based on experience of four high-volume COVID-19 hospitals in Northern Italy. METHODS: All cases of COVID-19 in-hospital patients undergoing duplex ultrasound (DUS) for clinically suspected DVT between March 1(st) and April 25(th) 2020 were reviewed. Demographics and clinical data of all patients with confirmed DVT were recorded. Computed Tomography Pulmonary Angiographies of the same population were also examined looking for signs of PE. RESULTS: of 101 DUS performed, 42 were positive for DVT, 7 for superficial thrombophlebitis and 24 for PE, 8 of which associated with a DVT. Most had a moderate (43.9%) or mild (16.9%) pneumonia. All venous districts were involved. Time of onset varied greatly, but diagnosis was more frequent in the first two weeks since in-hospital acceptance (73.8%). Most PEs involved the most distal pulmonary vessels, and two thirds occurred in absence of a recognizable deep vein thrombosis. CONCLUSIONS: DVT, thrombophlebitis and PE are different aspects of COVID-19 procoagulant activity and they can arise regardless of severity of respiratory impairment. All venous districts can be involved, including the pulmonary arteries, where the high number and distribution of the thrombotic lesions without signs of DVT could hint a primitive thrombosis rather than embolism.


title: Time-Varying COVID-19 Reproduction Number in the United States

text: The basic reproduction number is the average number of people to whom an infected person transmits the infection when virtually all individuals in a population are susceptible. We sought to calculate the current reproduction number for COVID-19 for each state in the United States. For the entire United States, the reproduction number declined from 4.02 to 1.51 between March 17 and April 1, 2020. We also found that the reproduction number for COVID-19 has declined in most states over the past two weeks which suggests that social isolation measures may be having a beneficial effect.


title: Prevalence and risk factors for agents causing diarrhea (Coronavirus, Rotavirus, Cryptosporidium spp., Eimeria spp., and nematodes helminthes) according to age in dairy calves from Brazil

text: The present study attempted to verify the prevalence of and risk factors for diarrhea-causing agents in dairy calves from Brazil. Additionally, ages with a higher risk of occurrence for each agent were verified by means of the receiver operating characteristic (ROC) curve. The collections were performed on 39 farms, belonging to 29 municipalities located in eight states of Brazil. It was possible to conclude that the prevalence of Coronavirus, Rotavirus, Cryptosporidium spp., Eimeria spp., and nematodes was 7.20% (95% CI 4.54–9.78), 6.37% (95% CI 3.85–8.89), 51.52% (95% CI 45.26–55.57), 3.46% (95% CI 2.24–4.67), and 3.46% (95% CI 2.24–4.67), respectively. Ages with higher probabilities of occurrence of these diseases in calves were < 10, > 8, > 6, > 37, and > 36 days, respectively. Diarrhea occurred more significantly (P < 0.0001) in animals less than 21 days old and mainly on those receiving milk through automatic feeders (P < 0.001). Cryptosporidium spp. were a risk factor for the occurrence of Rotavirus, and vice versa (P = 0.0039) and presented a positive correlation with Coronavirus (P = 0.0089). Calves that drink water from rivers, streams, and ponds had a higher chance of being infected by Eimeria spp. (P < 0.0001), as well as developing infection by nematodes (P < 0.0001). The results found in this study highlight the importance of studying the agents of diarrhea together, once they act as coinfection where the losses triggered for the owners will involve some of these agents simultaneously.


Exposure and Seroconversion to SARS-CoV-2 Among Obstetric Healthcare Providers Following a Contained Outbreak


title: Tunicamycin resistant glycosylation of a coronavirus glycoprotein: Demonstration of a novel type of viral glycoprotein

text: Abstract Tunicamycin has different effects on the glycosylation of the two envelope glycoproteins of mouse hepatitis virus (MHV), a coronavirus. Unlike envelope glycoproteins of other viruses, the transmembrane glycoprotein El is glycosylated normally in the presence of tunicamycin. This suggests that glycosylation of El does not involve transfer of core oligosaccharides from dolichol pyrophosphate intermediates to asparagine residues, but may occur by 0-linked glycosylation of serine or threonine residues. Synthesis of the peplomeric glycoprotein E2 is not readily detectable in the presence of tunicamycin. Inhibition of N-linked glycosylation of E2 by tunicamycin either prevents synthesis or facilitates degradation of the protein moiety of E2. Radiolabeling with carbohydrate precursors and borate gel electrophoresis of glycopeptides show that different oligcsaccharide side chains are attached to El and E2. The two coronavirus envelope glycoproteins thus appear to be glycosylated by different mechanisms. In tunicamycin-treated cells, noninfectious virions lacking peplomers are formed at intracytoplasmic membranes and released from the cells. These virions contain normal amounts of nucleocapsid protein and glycosylated El, but lack E2. Thus the transmembrane glycoprotein El is the only viral glycoprotein required for the formation of the viral envelope or for virus maturation and release. The peplomeric glycoprotein E2 appears to be required for attachment to virus receptors on the plasma membrane. The coronavirus envelope envelope glycoprotein E1 appears to be a novel type of viral glycoprotein which is post-translationally glycosylated by a tunicamycin-resistant process that yields oligosaccharide side chains different from those of N-linked glycoproteins. These findings suggest that El may be particularly useful as a model for studying the biosynthesis, glycosylation, and intracellular transport of 0-linked glycoproteins.


COVID-19 Lockdown Learning: The uprising of Virtual Teaching


title: Use of SARS‐CoV‐2 infected deceased organ donors: Should we always “just say no?”

text: In the context of a rapidly evolving pandemic, multiple organizations have released guidelines stating that all organs from potential deceased donors with SARS‐CoV‐2 infection should be deferred, including from otherwise medically eligible donors found to have mild or asymptomatic SARS‐CoV‐2 discovered on routine donor screening. In this manuscript, we critically examine the available data on the risk of transmission of SARS‐CoV‐2 through organ transplantation. The isolation of SARS‐CoV‐2 from non‐lung clinical specimens, the detection of SARS‐CoV‐2 in autopsy specimens, previous experience with the related coronaviruses SARS‐CoV and MERS‐CoV, and the vast experience with other common RNA respiratory viruses are all addressed. Taken together, these data provide little evidence to suggest the presence of intact transmissible SARS‐CoV in organs that can potentially be transplanted, specifically liver and heart. Other considerations including ethical, financial, societal, and logistical concerns are also addressed. We conclude that, for selected patients with high waitlist mortality, transplant programs should consider accepting heart or liver transplants from deceased donors with SARS‐CoV‐2 infection.


title: The Collaborative Cross Resource for Systems Genetics Research of Infectious Diseases

text: An increasing body of evidence highlights the role of host genetic variation in driving susceptibility to severe disease following pathogen infection. In order to fully appreciate the importance of host genetics on infection susceptibility and resulting disease, genetically variable experimental model systems should be employed. These systems allow for the identification, characterization, and mechanistic dissection of genetic variants that cause differential disease responses. Herein we discuss application of the Collaborative Cross (CC) panel of recombinant inbred strains to study viral pathogenesis, focusing on practical considerations for experimental design, assessment and analysis of disease responses within the CC, as well as some of the resources developed for the CC. Although the focus of this chapter is on viral pathogenesis, many of the methods presented within are applicable to studies of other pathogens, as well as to case–control designs in genetically diverse populations.


title: Monitoring Proteolytic Activity in Real Time: A New World of Opportunities for Biosensors

text: Proteases play a pivotal role in several biological processes, from digestion, cell proliferation, and differentiation to fertility. Deregulation of protease metabolism can result in several pathological conditions (i.e., cancer, neurodegenerative disorders, and others). Therefore, monitoring proteolytic activity in real time could have a fundamental role in the early diagnosis of these diseases. Herein, the main approaches used to develop biosensors for monitoring proteolytic activity are reviewed. A comparison of the advantages and disadvantages of each approach is provided along with a discussion of their importance and promising opportunities for the early diagnosis of severe diseases. This new era of biosensors can be characterized by the ability to control and monitor biological processes, ultimately improving the potential of personalized medicine.


title: Modeling the trend of coronavirus disease 2019 and restoration of operational capability of metropolitan medical service in China: a machine learning and mathematical model-based analysis

text: BACKGROUND: To contain the outbreak of coronavirus disease 2019 (COVID-19) in China, many unprecedented intervention measures are adopted by the government. However, these measures may interfere in the normal medical service. We sought to model the trend of COVID-19 and estimate the restoration of operational capability of metropolitan medical service in China. METHODS: Real-time data of COVID-19 and population mobility data were extracted from open sources. SEIR (Susceptible, Exposed, Infectious, Recovered) and neural network models (NNs) were built to model disease trends in Wuhan, Beijing, Shanghai and Guangzhou. Combined with public transportation data, Autoregressive Integrated Moving Average (ARIMA) model was used to estimate the accumulated demands for nonlocal hospitalization during the epidemic period in Beijing, Shanghai and Guangzhou. RESULTS: The number of infected people and deaths would increase by 45% and 567% respectively, given that the government only has implemented traffic control in Wuhan without additional medical professionals. The epidemic of Wuhan (measured by cumulative confirmed cases) was predicted to reach turning point at the end of March and end in later April, 2020. The outbreak in Beijing, Shanghai and Guangzhou was predicted to end at the end of March and the medical service could be fully back to normal in middle of April. During the epidemic, the number of nonlocal inpatient hospitalizations decreased by 69.86%, 57.41% and 66.85% in Beijing, Shanghai and Guangzhou respectively. After the end of epidemic, medical centers located in these metropolises may face 58,799 (95% CI 48926–67,232) additional hospitalization needs in the first month. CONCLUSION: The COVID-19 epidemic in China has been effectively contained and medical service across the country is expected to return to normal in April. However, the huge unmet medical needs for other diseases could result in massive migration of patients and their families, bringing tremendous challenges for medical service in major metropolis and disease control for the potential asymptomatic virus carrier.


The legal determinants of health: harnessing the power of law for global health and sustainable development


Acute pancreatitis in a COVID‐19 patient


title: Maximizing virtual meetings and conferences: a review of best practices

text: PURPOSE: In the current COVID-19 pandemic, it is more important than ever to maximize communication in the scientific and medical community. In the context of academic meetings and conferences, there is the growing need for a set of guidelines secondary to the COVID-19 pandemic, and the growing environmental and economic challenges that large academic and medical conferences face. These Virtual Meetings Best Practices were established in response to the scant evidence and guidance on the topic. METHODS: These best practice guidelines were developed from a scoping review of peer-reviewed literature, grey literature and lay literature. MEDLINE and Embase databases were scoped for relevant, non-duplicate articles. For lay articles, Google searches were utilized. The recommendations that comprise this document are a compilation of nonexperimental descriptive studies (e.g. case studies) and expert committee reports, opinions and/or experience of respected authorities, and lay articles. RESULTS: We identified four phases of the meeting cycle: Pre-planning considerations, Planning, Accomplishing conference goals through execution, gauging Response and Engaging the target audience for future cycles (PrePARE). Akin to the Plan, Do, Study, Act Cycle of quality improvement interventions, this document is meant to drive meaningful initial and subsequent interventions in the meetings of the medical and academic community. This covers actions and preparation for registration, scheduling, speakers, attendees, event type, technology, monetization/marketing, dealing with disruptions, post-event deliverables, response and engagement strategies. Enhanced access to integrated, high-quality and efficient virtual meetings will establish a new norm as an effective alternative for innovative health research, education and information dissemination in orthopaedics and beyond. CONCLUSIONS: Given the uncertainty of whether large in-person gatherings will be permitted, advisable or responsible later into the summer of 2020 and beyond, these guidelines will aid events being converted and scheduled as virtual-only meetings. As we move forward in the era of increased utility and utilization of virtual conferencing, these guidelines will serve as a benchmark and standard for surgeons in the field. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00264-020-04615-9) contains supplementary material, which is available to authorized users.


A Canadian perspective on coronavirus disease-19 and neurosurgical residency training


title: Cardiovascular comorbidity and its impact on patients with Covid-19

text: Comorbid hypertension correlates with poorer outcomes in patients with Covid-19.


title: Antibody signature induced by SARS-CoV-2 spike protein immunogens in rabbits

text: Multiple vaccine candidates against SARS-CoV-2 based on viral spike protein are under development. However, there is limited information on the quality of antibody responses generated with these vaccine modalities. To better understand antibody responses induced by spike protein-based vaccines, we performed a qualitative study by immunizing rabbits with various SARS-CoV-2 spike protein antigens: S-ectodomain (S1+S2) (aa 16-1213), which lacks the cytoplasmic and transmembrane domains (CT-TM), the S1 domain (aa 16-685), the receptor-binding domain (RBD) (aa 319-541), and the S2 domain (aa 686-1213, lacking the RBD, as control). Resulting antibody quality and function were analyzed by enzyme linked immunosorbent assay (ELISA), receptor binding domain (RBD) competition assay, surface plasmon resonance (SPR) against different spike proteins in native conformation, and neutralization assays. All three antigens (S1+S2 ectodomain, S1 domain, and RBD), but not S2, generated strong neutralizing antibodies against SARS-CoV-2. Vaccination-induced antibody repertoire was analyzed by SARS-CoV-2 spike genome fragment phage display libraries (SARS-CoV-2 GFPDL), which identified immunodominant epitopes in the S1, S1-RBD, and S2 domains. Furthermore, these analyses demonstrated that the RBD immunogen elicited a higher antibody titer with 5-fold higher affinity antibodies to native spike antigens compared with other spike antigens; and antibody affinity correlated strongly with neutralization titers. These findings may help guide rational vaccine design and facilitate development and evaluation of effective therapeutics and vaccines against COVID-19 disease.


title: Handwashing practice and the use of personal protective equipment among medical students after the SARS epidemic in Hong Kong

text: BACKGROUND: Hand hygiene is an important element of infection control. We conducted 2 surveys on hand hygiene practices and use of personal protective equipment among medical students during and after the outbreak of severe acute respiratory syndrome (SARS) to study its impact on their personal hygiene practice when they contacted patients. METHODS: Two cross-sectional surveys were conducted among medical students in their clinical training years (years 3-5) in a teaching hospital (at which the first and major SARS outbreak occurred) in March 2003 and August 2004, respectively. RESULTS: Prior to the recognition of the SARS outbreak in March 2003, 35.2% of the students washed their hands before and 72.5% after they physically examined patients in the wards. None of the students wore masks during history taking and physical examination. In the 2004 survey, the corresponding proportions were 60.3% and 100%, respectively, and 86.1% and 93.8% of students wore masks during history taking and physical examination, respectively. Attitudes to handwashing and perception of infection risk were not significantly associated with handwashing practice, whereas peer behavior might be a significant influencing factor. CONCLUSION: A significant improvement in compliance with hand hygiene practice was found after the SARS outbreak.


Progress in identifying the aetiologies of infectious foal diarrhoea


title: The effect of regionalization on outcome in pulmonary lobectomy: A Canadian national study

text: Objective To examine the effect of regionalization of thoracic surgery services in Canada by evaluating change over time in hospital volumes of pulmonary lobectomy and its impact on length of stay and in-hospital mortality. Methods Data on pulmonary lobectomy between 1999 and 2007 were abstracted from the Canadian Institute for Health Information Discharge Abstract Database. In-hospital mortality was analyzed by logistic regression, and log-transformed length of stay was analyzed by linear regression. Cross-sectional analysis of hospital volume, in-hospital mortality, and length of stay was performed, controlling for clustering. Within-hospital changes in annual volume on outcome was analyzed using multivariable logistic regression, controlling for Charlson comorbidity index and other confounders. Results Of 19,732 patients, 10, 281 (52%) were male, with an average age of 63.3 years. There was a 45% (95% confidence interval, 21–61; P = .001) relative risk reduction in in-hospital mortality with a 19% reduction in length of stay (95% confidence interval, 12–25; P < .0001). On comparison of volume between hospitals, an increase of 20 cases was associated with a 15% relative risk reduction (95% confidence interval, 9–19; P < .0001) in in-hospital mortality and a 5% relative decrease (95% confidence interval, 3–7; P < .001) in length of stay. Within hospitals there was a nonsignificant relationship between volume and in-hospital mortality. Conclusions In-hospital mortality and length of stay for lobectomies have decreased in Canada. In multivariate analysis, volume was associated with improved in-hospital mortality, but there was no reduction in mortality when volume was increased within a given hospital. However, the proportion of patients treated in high-volume centers has increased over time, inferring the importance of high-volume centers in improved outcomes. This supports regionalization policies for pulmonary lobectomy.


title: Commentaire sur un article d'Alberto Quintavalla & Klaus Heine. Reconnaître l'importance du droit à la santé comme condition préalable à la hiérarchisation des droits

text: Résumé Ce commentaire, qui porte sur l'article de Heine et Quintavalla intitulé "Priorités et droits de l'homme", examine la position des auteurs selon laquelle, si le droit à la vie et les autres droits civils et politiques sont aussi importants que la santé et les autres droits sociaux, il est nécessaire de hiérarchiser les types de droits dans une certaine mesure, car tous les droits ne peuvent être mis en œuvre simultanément. Ce commentaire rejoint la contestation par Heine et Quintavalla de l'argument commun selon lequel les droits civils et politiques sont d'une importance supérieure [1-3]. Mais ce commentaire va plus loin, en suggérant qu'avant qu'une société ne commence à donner la priorité à la mise en œuvre des droits de l'homme, elle doit d'abord s'assurer que le droit à la santé est effectivement aussi important que les droits civils et politiques. Ce commentaire utilise l'exemple des tribunaux nationaux pour montrer comment l'engagement judiciaire en faveur du droit à la santé a commencé à effacer la frontière entre les catégories de droits. Il suggère qu'une plus grande interconnexion entre le droit à la santé et les autres droits a également rendu beaucoup plus difficile l'établissement d'une relation hiérarchique. Ainsi, avant que la mise en œuvre puisse avoir un ordre défini, les États doivent d'abord parvenir à une compréhension commune de l'importance égale, voire supérieure, du droit à la santé. Abstract This commentary, on Heine and Quintavalla’s article Priorities and Human Rights, considers the authors’ position that, while the right to life and other civil and political rights are equally as important as health and other social rights, some degree of prioritizing types of rights is necessary because all rights cannot be implemented simultaneously. This commentary concurs with Heine and Quintavalla’s challenge to the common argument that civil and political rights are of higher importance [1-3]. But this commentary goes further, in suggesting that before a society begins to prioritize implementation of human rights, it must first secure the basic understanding that the right to health is indeed equally important to civil and political rights. This commentary uses the example of national courts to show how judicial engagement with the right to health has begun to chip away at the boundary between the categories of rights. It suggests that greater interconnection among health and other rights has also made mapping out a hierarchical relationship far more difficult. Thus, before implementation can have any defined order, states must first come to a shared understanding regarding the equal if not greater importance of the right to health.


title: Prevention of infectious diseases among international pediatric travelers: Considerations for clinicians

text: An estimated 1.9 million children travel overseas annually. Infectious disease risks associated with international travel are diverse and depend on the destination, planned activities, and baseline medical history. Children have special needs and vulnerabilities that should be addressed when preparing for travel abroad. Children should have a pretravel health assessment that includes recommendations for both routine and special travel-related vaccination; malaria chemoprophylaxis, if indicated; and prevention counseling regarding insect and animal exposures, food and water safety, and avoiding injuries. Special consideration should be given to children with chronic diseases. Families should be given anticipatory guidance for management of potential illnesses and information about the location of medical resources overseas.