title: Optimization of Resources and Modifications in Acute Ischemic Stroke Care in Response to the Global COVID-19 Pandemic

text: Abstract Background: The COVID-19 pandemic has presented unprecedented challenges to healthcare organizations worldwide. A steadily rising number of patients requiring intensive care, a large proportion from racial and ethnic minorities, demands creative solutions to provide high-quality care while ensuring healthcare worker safety in the face of limited resources. Boston Medical Center has been particularly affected due to the underserved patient population we care for and the increased risk of ischemic stroke in patients with COVID-19 infection. Methods: We present protocol modifications developed to manage patients with acute ischemic stroke in a safe and effective manner while prioritizing judicious use of personal protective equipment and intensive care unit resources. Conclusion: We feel this information will benefit other organizations facing similar obstacles in caring for the most vulnerable patient populations during this ongoing public health crisis.


A dose of reality


docid: qwylfihl

title: Let Us Not Forget Cardiovascular Diseases During COVID-19 Pandemic: the Role of Cardiac Prevention and Rehabilitation

text: During novel coronavirus disease (COVID-19) pandemic, major focus of health service is on mitigating the spread of infection and treating the acute severe respiratory syndrome of affected patients. However, from available initial data, it has been shown that cardiovascular and metabolic diseases are responsible for a worse clinical outcome of COVID-19 patients and, on the other hand, myocardial damage might occur as a consequence of infection. Therefore, we propose not to forget the heart during pandemic and to focus on cardiac care in at least three phases: prevention, acute phase, and rehabilitation. We report rationale, scientific evidence, and clinical model for the proposed three-phase program.


title: Clinical and ethical challenges for emergency departments during communicable disease outbreaks: Can lessons from Ebola Virus Disease be applied to the COVID‐19 pandemic?

text: EDs fulfil a frontline function during public health emergencies (PHEs) and will play a pivotal role during the COVID‐19 pandemic. This perspective article draws on qualitative data from a longitudinal, ethnographic study of an Australian tertiary ED to illustrate the clinical and ethical challenges faced by EDs during PHEs. Interview data collected during the 2014 Ebola Virus Disease PHE of International Concern suggest that ED clinicians have a strong sense of professional responsibility, but this can be compromised by increased visibility of risk and sub‐optimal engagement from hospital managers and public health authorities. The study exposes the tension between a healthcare worker's right to protection and a duty to provide treatment. Given the narrow window of opportunity to prepare for a surge of COVID‐19 presentations, there is an immediate need to reflect and learn from previous experiences. To maintain the confidence of ED clinicians, and minimise the risk of moral injury, hospital and public health authorities must urgently develop processes to support ethical healthcare delivery and ensure adequate resourcing of EDs.


Development of SARS vaccines and therapeutics is still needed


title: OnabotulinumtoxinA infiltration and nerve blocks in patients with headache and neuralgia: safety recommendations to prevent SARS-CoV-2 infection

text: Abstract Introduction The COVID-19 pandemic has given rise to the need for changes in clinical practice, with new strategies to enable integrated care for patients with headache and neuralgia. Material and methods Given the high spreadability of SARS-CoV-2, new safety measures are required in such procedures as onabotulinumtoxinA infiltration and nerve blocks. Results We present a series of recommendations based on the measures implemented to prevent infection in our healthcare system. We differentiate between measures related to patients and physicians, to technique, to infrastructure (waiting room and consultation), and to healthcare management.


title: Characteristics of COVID-19 Clinical Trials in China Based on the Registration Data on ChiCTR and ClinicalTrials.gov

text: OBJECTIVE: This study aimed to evaluate the fundamental characteristics of coronavirus disease (COVID-19) clinical trials registered in China. METHODS: COVID-19 clinical trials registered in China were analyzed from databases on ChiCTR and ClinicalTrials.gov. The study designs, samples, primary end points, and intervention measures were evaluated. RESULTS: In total, 262 intervention clinical trials were retrieved on March 10, 2020. Overall, 181 (69.1%) trials involved two groups, 200 (76.3%) trials were randomized parallel trials, 24 (9.2%) trials were double blind, and 60.3% of trials included ≤100 participants. Sixty (22.9%) trials considered symptom improvement as the primary endpoint and 43 (16.4%) trials considered the rate or time at which the subjects became virus-free as the primary endpoint. Of 262 intervention studies, chemical drugs and biological products were studied in 105 (40.1%) intervention studies, of which antiviral drugs accounted for 15.3% and malaria drugs accounted for 8.4% of the studies. Among all trials, 27.9% of the studies used traditional Chinese medicine (TCM), 10.3% used cell therapy, and 5.0% used plasma therapy. CONCLUSION: This study is the first snapshot of the landscape of COVID-19 clinical trials registered in China and provided the basic features of clinical trial designs for the treatment and prevention of COVID-19 to offer useful information to guide future clinical trials on COVID-19 in other countries.


title: Telemedicine for housebound older persons during the Covid-19 pandemic

text: Targeting older at-risk patients with decision-making algorithms is a priority at a time when hospitals are receiving an influx of Covid-19 patients that may exceed their capacity. Such screening could likely be extended to primary care settings in order to identify older community dwellers with Covid-19, but also those experiencing the adverse consequences of prolonged home confinement. The Centre of Excellence on Longevity of McGill University (Quebec, Canada) designed a short assessment for Montreal’s housebound community-dwelling older adults. It acts as the first step in connecting older community dwellers who are housebound during the Covid-19 outbreak to telemedicine.


title: Do Peri-Transplant Respiratory Viral Infections Increase Incidence of Idiopathic Pneumonia Syndrome or Bronchiolitis Obliterans in Pediatric Pateints?

text: Background Upper respiratory viral infections are common in the pediatric population. Idiopathic pneumonia syndrome (IPS) and bronchiolitis obliterans (BO) are rare, but devastating and life-threatening complications post hematopoietic stem cell transplant (HSCT). It has been suggested in work by others that IPS and BO are consequences of early inflammation, and recent data support this hypothesis (Versluys et al, Translational and Clinical Immunology, 2018). Respiratory viral infections early in the peri-transplant period may result in inflammation leading to development of IPS and BO post HSCT. Objectives The primary objective of this study was to determine whether pre-transplant respiratory viral infection or colonization increase incidence of IPS and BO. We hypothesized that patients who acquire respiratory viral infections in the peri-transplant period have increased incidence of IPS and BO. Methods We abstracted and analyzed clinically collected data and compared the frequency of post-transplant respiratory viral complications with the presence of upper respiratory viral infections within 30 days prior to transplant. A Broncho alveolar lavage (BAL) or a nasal swab were used to identify upper respiratory viral infections. Epstein Barr virus (EBV), cytomegalovirus (CMV) and other upper respiratory viral infections were tested in 181 patients, transplanted between 2008 and 2018. Outcomes studied included IPS, BO, transplant associated thrombotic microangiopathy (TMA), graft versus host disease (GVHD), and overall survival (OS). Patients who did not have a BAL or a nasal swab within 30 days prior to transplant were excluded. Results Forty seven of 181 patients had a positive BAL or nasal swab prior to HSCT (group A). There were 53 documented respiratory viral infections in group A. Two tested positive for either coronavirus, herpes simplex virus (HSV) or para-influenza virus, 3 tested positive for adenovirus, human herpes 6, influenza, or respiratory syncytial virus (RSV), EBV and CMV were detected in 9 patients, 1 patient had human metapneumovirus and there were 16 rhino virus infections documented prior to HSCT. Some patients tested positive for more than 1 respiratory viral infection at the time of testing. Results of our study are summarized below in Figure 1. Conclusion Contrary to our hypothesis, our data do not support an association between upper respiratory viral infections prior to transplant and post-transplant IPS or BO. Our data may differ from the findings of others due to a relatively small number of events in our population, or to differences in patient populations being studied, or to differences in transplant strategies.


title: New approach to identifying proper thresholds for a heat warning system using health risk increments

text: Abstract Background A critical adaptation strategy for reducing heat-related health risk under climate change is to establish a heat warning system with a proper threshold that requires evaluation of heat-health relationships using empirical data. Objectives This work presents a new approach to selecting proper health-based thresholds for a heat warning system which are different from thresholds of heat-health relationship. Methods The proposed approach examined heat-health relationships through analyzing 15 years of health records with a modified generalized additive model (GAM), compared risk ratio increments (RRIs) of threshold candidates against a reference, assessed frequency of days above these candidates, and presented results graphically for easy communication. The candidate with the maximum RRI and proper occurring frequency is potentially the best threshold. Three heat indicators, including wet-bulb globe temperature (WBGT), temperature (T), and apparent temperature (AT), as well as three health outcomes, including all-cause mortality, heat-related hospital admissions, and heat-related emergency visits were evaluated. Results Risk ratios for all three health outcomes showed a consistent rising trend with increasing threshold candidates for all three heat indicators among different age and gender groups. WBGT had the most obvious increasing trend of RRIs with the three health outcomes. The maximum RRI was observed in heat-related emergency visits (242%), followed by heat-related hospital admissions (73%), and all-cause mortality (9%). The RRIs assessed for the three health outcomes pointed to the same thresholds, 33.0 °C, 34.0 °C, and 37.5 °C for WBGT, T, and AT, respectively. The number of days above these thresholds and for warning to be issued ranged between 0 and 7 days during 2000–2014. Discussion This study demonstrated a new approach to determining heat-warning thresholds with different heat indicators and health outcomes. The proposed approach provides a straightforward, feasible, and flexible scientific tool that assists the authorities around the world in selecting a proper threshold for a heat warning system.


title: Modified Vaccinia Virus Ankara (MVA) as Production Platform for Vaccines against Influenza and Other Viral Respiratory Diseases

text: Respiratory viruses infections caused by influenza viruses, human parainfluenza virus (hPIV), respiratory syncytial virus (RSV) and coronaviruses are an eminent threat for public health. Currently, there are no licensed vaccines available for hPIV, RSV and coronaviruses, and the available seasonal influenza vaccines have considerable limitations. With regard to pandemic preparedness, it is important that procedures are in place to respond rapidly and produce tailor made vaccines against these respiratory viruses on short notice. Moreover, especially for influenza there is great need for the development of a universal vaccine that induces broad protective immunity against influenza viruses of various subtypes. Modified Vaccinia Virus Ankara (MVA) is a replication-deficient viral vector that holds great promise as a vaccine platform. MVA can encode one or more foreign antigens and thus functions as a multivalent vaccine. The vector can be used at biosafety level 1, has intrinsic adjuvant capacities and induces humoral and cellular immune responses. However, there are some practical and regulatory issues that need to be addressed in order to develop MVA-based vaccines on short notice at the verge of a pandemic. In this review, we discuss promising novel influenza virus vaccine targets and the use of MVA for vaccine development against various respiratory viruses.


title: Chapter 5 Advance detection technologies for select biothreat agents

text: Abstract This chapter provides a comprehensive update about various technological developments in the field of biothreat agent detection. We have attempted to provide the reader with all the basic information starting with the culture considered as gold standard of diagnosis, immunological assays like the immunochromatographic test (ICT) which includes the lateral flow rapid strip test, flow through spot test and molecular assays, polymerase chain reaction (PCR), real-time RT-PCR, isothermal gene amplification assays, next-generation sequencing (NGS) technology, etc. One major highlight of the chapter includes bio-monitoring and aerosol generation technologies. We have also provided information about the sensor technologies nanomaterials biosensors, various analytical techniques besides various instrumental technologies like mass spectroscopy and Raman chemical imaging. The last part of the chapter is devoted to some newer technologies like biodetectors where we have given details about those that are currently commercially available.


title: Clinical characteristics of 225 patients with COVID-19 in a tertiary Hospital near Wuhan, China

text: Abstract Background The 2019 coronavirus disease (COVID-19) was first identified in Wuhan, Hubei, China in December 2019, caused by a novel coronavirus (SARS-CoV-2). There is a need to study the clinical features of patients in a hospital near Wuhan. Objective To identify clinical features of patients with COVID-19 in a tertiary hospital near Wuhan. Study design General information, clinical manifestations, laboratory data, and computed tomography (CT) data were collected for 225 patients diagnosed of COVID-19 admitted between January 20 and February 14, 2020, to the Hanchuan City People’s Hospital. Results The patients included 120 male and 105 females who had no connection to the Wuhan Huanan Seafood Market. Their average age was 50 ± 14 years. The major clinical symptoms were fever (84.44% of patients), cough (56.44% of patients), and dyspnea (4.00% of patients); 3.56%–22.67% of subjects suffered from expectoration, fatigue, chills, headache, chest pain, and pharyngalgia. Hypertension was present in 20.89% of patients. The counts of white blood cells (WBCs) and lymphocytes were normal or decreased in 86.67% and 99.11% of patients. CRP was increased in 86.22% of patients, PCT in 10.67%, and ESR in 90.22%. CT showed that 86.22% of patients had multiple patchy glassy shadows in both lungs, particularly in the peripheral area. Thirty-seven (16.44%) patients were diagnosed with severe COVID-19. Methylprednisolone was administered in 44.44% of cases. The mortality among the patients was 0.89%. Conclusions Clinical characteristics of COVID-19 patients in the tertiary hospital near Wuhan are very similar to those found in Wuhan, but the lower mortality.


title: On the stability of sequences inserted into viral genomes

text: Viruses are widely used as vectors for heterologous gene expression in cultured cells or natural hosts, and therefore a large number of viruses with exogenous sequences inserted into their genomes have been engineered. Many of these engineered viruses are viable and express heterologous proteins at high levels, but the inserted sequences often prove to be unstable over time and are rapidly lost, limiting heterologous protein expression. Although virologists are aware that inserted sequences can be unstable, processes leading to insert instability are rarely considered from an evolutionary perspective. Here, we review experimental work on the stability of inserted sequences over a broad range of viruses, and we present some theoretical considerations concerning insert stability. Different virus genome organizations strongly impact insert stability, and factors such as the position of insertion can have a strong effect. In addition, we argue that insert stability not only depends on the characteristics of a particular genome, but that it will also depend on the host environment and the demography of a virus population. The interplay between all factors affecting stability is complex, which makes it challenging to develop a general model to predict the stability of genomic insertions. We highlight key questions and future directions, finding that insert stability is a surprisingly complex problem and that there is need for mechanism-based, predictive models. Combining theoretical models with experimental tests for stability under varying conditions can lead to improved engineering of viral modified genomes, which is a valuable tool for understanding genome evolution as well as for biotechnological applications, such as gene therapy.


title: Conformational Flexibility of a Short Loop near the Active Site of the SARS-3CLpro is Essential to Maintain Catalytic Activity

text: The SARS 3C-like proteinase (SARS-3CLpro), which is the main proteinase of the SARS coronavirus, is essential to the virus life cycle. This enzyme has been shown to be active as a dimer in which only one protomer is active. However, it remains unknown how the dimer structure maintains an active monomer conformation. It has been observed that the Ser139-Leu141 loop forms a short 3(10)-helix that disrupts the catalytic machinery in the inactive monomer structure. We have tried to disrupt this helical conformation by mutating L141 to T in the stable inactive monomer G11A/R298A/Q299A. The resulting tetra-mutant G11A/L141T/R298A/Q299A is indeed enzymatically active as a monomer. Molecular dynamics simulations revealed that the L141T mutation disrupts the 3(10)-helix and helps to stabilize the active conformation. The coil-3(10)-helix conformational transition of the Ser139-Leu141 loop serves as an enzyme activity switch. Our study therefore indicates that the dimer structure can stabilize the active conformation but is not a required structure in the evolution of the active enzyme, which can also arise through simple mutations.


title: Immunopathogenesis of Severe Acute Respiratory Disease in Zaire ebolavirus-Infected Pigs

text: Ebola viruses (EBOV) are filamentous single-stranded RNA viruses of the family Filoviridae. Zaire ebolavirus (ZEBOV) causes severe haemorrhagic fever in humans, great apes and non-human primates (NHPs) with high fatality rates. In contrast, Reston ebolavirus (REBOV), the only species found outside Africa, is lethal to some NHPs but has never been linked to clinical disease in humans despite documented exposure. REBOV was isolated from pigs in the Philippines and subsequent experiments confirmed the susceptibility of pigs to both REBOV and ZEBOV with predilection for the lungs. However, only ZEBOV caused severe lung pathology in 5–6 weeks old pigs leading to respiratory distress. To further elucidate the mechanisms for lung pathology, microarray analysis of changes in gene expression was performed on lung tissue from ZEBOV-infected pigs. Furthermore, systemic effects were monitored by looking at changes in peripheral blood leukocyte subsets and systemic cytokine responses. Following oro-nasal challenge, ZEBOV replicated mainly in the respiratory tract, causing severe inflammation of the lungs and consequently rapid and difficult breathing. Neutrophils and macrophages infiltrated the lungs but only the latter were positive for ZEBOV antigen. Genes for proinflammatory cytokines, chemokines and acute phase proteins, known to attract immune cells to sites of infection, were upregulated in the lungs, causing the heavy influx of cells into this site. Systemic effects included a decline in the proportion of monocyte/dendritic and B cells and a mild proinflammatory cytokine response. Serum IgM was detected on day 5 and 6 post infection. In conclusion, a dysregulation/over-activation of the pulmonary proinflammatory response may play a crucial role in the pathogenesis of ZEBOV infection in 5–6 weeks old pigs by attracting inflammatory cells to the lungs.


title: Helicity propensity and interaction of synthetic peptides from heptad-repeat domains of herpes simplex virus 1 glycoprotein H: A circular dichroism study

text: Abstract The secondary structure of two synthetic peptides from heptad-repeat domains of herpes simplex virus 1 glycoprotein H was determined by circular dichroism. In particular, the propensity of these peptides to assume an ordered structure was investigated upon by changing the solvent's polarity and the temperature. A reduction of solvent polarity led to a significant increase in the α-helix content in the case of HR1, whereas only a slight change in the secondary structure was observed in the case of HR2. In both cases the conformational change followed a two-state transition model. The interaction of the peptides was monitored by the conformational change in the mixture with respect to the single peptides. However, formation of the complex did not significantly enhance thermal stability. A reliable estimation of the secondary structure was obtained by optimising the experimental conditions to collect CD data down to 180 nm, and by comparing the structure data yielded by different software packages.


title: An Inverse Relationship between Hyperuricemia and Mortality in Patients Undergoing Continuous Ambulatory Peritoneal Dialysis

text: Background: The results have been inconsistent with regards to the impact of uric acid (UA) on clinical outcomes both in the general population and in patients with chronic kidney disease. The aim of this study was to study the influence of serum UA levels on mortality in patients undergoing continuous ambulatory peritoneal dialysis. Methods: Data on 492 patients from a single peritoneal dialysis unit were retrospectively analyzed. The mean age of the patients was 53.5 ± 15.3 years, with 52% being female (n = 255). The concomitant comorbidities at the start of continuous ambulatory peritoneal dialysis (CAPD) encompassed diabetes mellitus (n = 179, 34.6%), hypertension (n = 419, 85.2%), and cardiovascular disease (n = 186, 37.9%). The study cohort was divided into sex-specific tertiles according to baseline UA level. A Cox proportional hazard model was used to calculate hazard ratios (HRs) of all-cause, cardiovascular, and infection-associated mortality with adjustments for demographic and laboratory data, medications, and comorbidities. Results: Multivariate Cox regression analysis showed that, using UA tertile 1 as the reference, the adjusted HR of all-cause, cardiovascular, and infection-associated mortality for tertile 3 was 0.4 (95% confidence interval (CI) 0.24–0.68, p = 0.001), 0.4 (95% CI 0.2–0.81, p = 0.01), and 0.47 (95% CI 0.19–1.08, p = 0.1). In the fully adjusted model, the adjusted HRs of all-cause, cardiovascular, and infection-associated mortality for each 1-mg/dL increase in UA level were 0.84 (95% CI, 0.69–0.9, p = 0.07), 0.79 (95% CI, 0.61–1.01, p = 0.06), and 0.79 (95% CI, 0.48–1.21, p = 0.32) for men and 0.57 (95% CI, 0.44–0.73, p < 0.001), 0.6 (95% CI, 0.41–0.87, p = 0.006), and 0.41 (95% CI, 0.26–0.6, p < 0.001) for women, respectively. Conclusions: Higher UA levels are associated with lower risks of all-cause, cardiovascular and infection-associated mortality in women treated with continuous ambulatory peritoneal dialysis.


title: Novel Antiretroviral Structures from Marine Organisms

text: In spite of significant advancements and success in antiretroviral therapies directed against HIV infection, there is no cure for HIV, which scan persist in a human body in its latent form and become reactivated under favorable conditions. Therefore, novel antiretroviral drugs with different modes of actions are still a major focus for researchers. In particular, novel lead structures are being sought from natural sources. So far, a number of compounds from marine organisms have been identified as promising therapeutics for HIV infection. Therefore, in this paper, we provide an overview of marine natural products that were first identified in the period between 2013 and 2018 that could be potentially used, or further optimized, as novel antiretroviral agents. This pipeline includes the systematization of antiretroviral activities for several categories of marine structures including chitosan and its derivatives, sulfated polysaccharides, lectins, bromotyrosine derivatives, peptides, alkaloids, diterpenes, phlorotannins, and xanthones as well as adjuvants to the HAART therapy such as fish oil. We critically discuss the structures and activities of the most promising new marine anti-HIV compounds.


title: Azadirachta indica A. Juss Ameliorates Mouse Hepatitis Virus-Induced Neuroinflammatory Demyelination by Modulating Cell-to-Cell Fusion in an Experimental Animal Model of Multiple Sclerosis

text: Mouse hepatitis virus (MHV)-induced murine neuroinflammation serves as a model to study acute meningoencephalomyelitis, hepatitis, and chronic neuroinflammatory demyelination; which mimics certain pathologies of the human neurologic disease, multiple sclerosis (MS). MHV-induced acute neuroinflammation occurs due to direct glial cell dystrophy instigated by central nervous system (CNS)-resident microglia and astrocytes, in contrast to peripheral CD4+T cell-mediated myelin damage prevalent in the experimental autoimmune encephalomyelitis (EAE) model of MS. Viral envelope Spike glycoprotein-mediated cell-to-cell fusion is an essential mechanistic step for MHV-induced CNS pathogenicity. Although Azadirachta indica (Neem), a traditional phytomedicine, is known for its anti-inflammatory, anti-fungal, and spermicidal activities, not much is known about anti-neuroinflammatory properties of its bark (NBE) in MHV-induced acute neuroinflammation and chronic demyelination. Recombinant demyelinating MHV strain (RSA59) was preincubated with NBE to arrest the infection-initiation event, and its effect on viral replication, viral transcription, cytokine expression, and successive pathogenicity were investigated in vitro and in vivo. Virus-free Luciferase assay explained NBE’s anti-virus-to-cell fusion activity in vitro. Intracranial inoculation of RSA59 preincubated with NBE into the mouse brain significantly reduces acute hepatitis, meningoencephalomyelitis, and chronic progressive demyelination. Additionally, NBE effectively restricts viral entry, dissemination in CNS, viral replication, viral transcription, and expression of the viral nucleocapsid and inflammatory cytokines. From mechanistic standpoints, RSA59 preincubated with NBE reduced viral entry, viral replication and cell-to-cell fusion, as a mode of viral dissemination. Moreover, intraperitoneal injection with NBE (25 mg/kg B.W.) into mice revealed a significant reduction in viral Nucleocapsid protein expression in vivo. Conclusively, A. indica bark extract may directly bind to the virus-host attachment Spike glycoprotein and suppresses MHV-induced neuroinflammation and neuropathogenesis by inhibiting cell-to-cell fusion and viral replication. Further studies will focus on combining bioanalytical assays to isolate potential NBE bioactive compound(s) that contribute towards the anti-viral activity of NBE.


title: Intranasal Inoculation with the Olfactory Bulb Line Variant of Mouse Hepatitis Virus Causes Extensive Destruction of the Olfactory Bulb and Accelerated Turnover of Neurons in the Olfactory Epithelium of Mice

text: Viral upper respiratory infections are the most common cause of clinical olfactory dysfunction, but the pathogenesis of dysosmia after viral infection is poorly understood. Biopsies of the olfactory mucosa in patients that complain of dysosmia after viral infection fall into two categories: one in which no olfactory epithelium is seen and another in which the epithelium is disordered and populated mainly by immature neurons. We have used intranasal inoculation with an olfactory bulb line variant of MHV to study the consequences of viral infection on peripheral olfactory structures. MHV OBLV has little direct effect on the olfactory epithelium, but causes extensive spongiotic degeneration and destruction of mitral cells and interneurons in the olfactory bulb such that the axonal projection from the bulb via the lateral olfactory tract is markedly reduced. Moreover, surviving mitral cells apparently remain disconnected from the sensory neuron input to the glomerular layer, judging from retrograde labeling studies using Dil. The damage to the bulb indirectly causes a persistent, long-term increase in the turnover of sensory neurons in the epithelium, i.e. the relative proportion of immature to mature sensory neurons and the rate of basal cell proliferation both increase. The changes that develop after inoculation with MHV OBLV closely resemble the disordering of the olfactory epithelium in some patient biopsies. Thus, damage to the olfactory nerve or bulb may contribute to a form of post-viral olfactory dysfunction and MHV OBLV is a useful model for studying the pathogenesis of this form of dysosmia.


title: The role of justice in developing critical minerals

text: It is a fundamental objective to transition towards a low-carbon economy worldwide which is supported by an international legal agreement – the 2015 Paris Agreement. In order to achieve this ambition, there is a need for new and more mineral extraction which is necessary for the technology for this low-carbon transition. These minerals are known as critical minerals and this article examines the role of justice needed in their development. The literature to-date lacks any holistic yet focused examination of the key elements of justice in the development of this industry. This conceptual article makes an original contribution that utilises an interdisciplinary perspective, legal geography, and explores key issues of justice that include distributive, procedural, restorative, recognition and cosmopolitan. The research identifies the key questions that need to be resolved under each element of justice and the unfortunate limited timeframes for action. Critical justice areas include taxation, environmental impact assessments, waste management, social license to operate, and cross-border actions. Resolving these issues will directly address societal issues of inequality and ensure a just transition to a low-carbon economy. Already there is a global race for critical minerals, and justice needs a stronger role in its development based on evidence to-date.


docid: fxuxqrap

title: Lack of graft-versus-host-like pathology in mercury-induced autoimmunity of Brown Norway rats

text: Abstract The repeated administration of mercury to Brown Norway (BN) rats induces the production of autoantibodies to laminin 1 and other autoantigens, accompanied by renal deposition of immunoglobulins and a membranous glomerulonephropathy. A graft-versus-host-like (GVHL) syndrome, characterized by widespread necrotizing leukocytoclastic vasculitis of the bowel, skin, and other tissues, has also been observed after mercury treatment of BN rats. These findings have suggested that the autoimmunity caused by the administration of mercury to BN rats may result as a xenobiotic-induced GVHL effect under the control of OX22+ T lymphocytes. However, previous studies of mercury-induced autoimmunity have never reported any evidence of GVHL lesions. Therefore, we have carefully examined various tissues from a large group of BN rats injected with HgCl2 to identify possible areas of inflammatory reactions that may have been unnoticed in previous investigations. In addition, we have determined by flow cytometry whether exposure to mercury results in percentage and numerical alterations of OX22+ or other lymphocyte subpopulations in lymphoid organs of HgCl2-treated BN rats. The present article confirms that mercury induces autoimmune responses to laminin 1 but does not corroborate the hypothesis of a GVHL syndrome regulated by OX22+ lymphocytes. First, changes in OX22+ cells during treatment with HgCl2 were infrequent and had no significant correlation with the kinetics of autoimmune responses to laminin 1. Second, we detected no GVHL lesions in skin and intestine of mercury-treated BN rats.


title: Lysosomotropic agents as HCV entry inhibitors

text: HCV has two envelop proteins named as E1 and E2 which play an important role in cell entry through two main pathways: direct fusion at the plasma membrane and receptor-mediated endocytosis. Fusion of the HCV envelope proteins is triggered by low pH within the endosome. Lysosomotropic agents (LA) such as Chloroquine and Ammonium chloride (NH(4)Cl) are the weak bases and penetrate in lysosome as protonated form and increase the intracellular pH. To investigate the antiviral effect of LA (Chloroquine and NH(4)Cl) on pH dependent endocytosis, HCV pseudoparticles (HCVpp) of 1a and 3a genotype were produced and used to infect liver cells. The toxicological effects of Chloroquine and NH(4)Cl were tested in liver cells through MTT cell proliferation assay. For antiviral screening of Chloroquine and NH(4)Cl, liver cells were infected with HCVpp of 3a and 1a genotype in the presence or absence of different concentrations of Chloroquine and NH4Cl and there luciferase activity was determined by using a luminometer. The results demonstrated that Chloroquine and NH(4)Cl showed more than 50% reduction of virus infectivity at 50 μM and 10 mM concentrations respectively. These results suggest that inhibition of HCV at fusion step by increasing the lysosomal pH will be better option to treat chronic HCV.


title: The role of routine versus random movements on the spread of disease in Great Britain

text: Mathematical models of infectious disease spread are important tools for assessing the threat of a novel pathogen and offer the best information for mitigating an outbreak. Here we present a metapopulation model of disease spread in Great Britain defined at the level of electoral wards. Using data from the United Kingdom 2001 census and the National Travel Survey to define the amount of travel performed by individuals between wards, we examine the effect of assumptions on the regularity of travel. Routine, daily commuter-type movements, characteristic of the working population are shown to lead to a slower epidemic spread compared to movements with random destinations. We demonstrate that routine movements slow down the epidemic spread compared to a standard metapopulation setting by up to 25%. We also show that spurious long distance movements present in the census data do not have a significant impact on the development of a potential epidemic in Great Britain.


title: COVID‐19: providing support for men with prostate cancer

text: Men with prostate cancer are understandably worried about the impact of COVID‐19 on their care. Prostate Cancer UK is helping to provide support and reassurance but the authors warn that men with prostate cancer must not be forgotten in the efforts to rebuild services after the threat of COVID‐19 becomes less pressing.


title: Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis

text: Severe acute respiratory syndrome (SARS) is an acute infectious disease that spreads mainly via the respiratory route. A distinct coronavirus (SARS‐CoV) has been identified as the aetiological agent of SARS. Recently, a metallopeptidase named angiotensin‐converting enzyme 2 (ACE2) has been identified as the functional receptor for SARS‐CoV. Although ACE2 mRNA is known to be present in virtually all organs, its protein expression is largely unknown. Since identifying the possible route of infection has major implications for understanding the pathogenesis and future treatment strategies for SARS, the present study investigated the localization of ACE2 protein in various human organs (oral and nasal mucosa, nasopharynx, lung, stomach, small intestine, colon, skin, lymph nodes, thymus, bone marrow, spleen, liver, kidney, and brain). The most remarkable finding was the surface expression of ACE2 protein on lung alveolar epithelial cells and enterocytes of the small intestine. Furthermore, ACE2 was present in arterial and venous endothelial cells and arterial smooth muscle cells in all organs studied. In conclusion, ACE2 is abundantly present in humans in the epithelia of the lung and small intestine, which might provide possible routes of entry for the SARS‐CoV. This epithelial expression, together with the presence of ACE2 in vascular endothelium, also provides a first step in understanding the pathogenesis of the main SARS disease manifestations. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


An Invited Commentary on “World Health Organization declares global emergency: A review of the 2019 novel Coronavirus (COVID-19)": Emergency or new reality?


title: COVID‐19 complicated by acute myocardial infarction with extensive thrombus burden and cardiogenic shock

text: A patient with coronavirus disease 19 (COVID‐19) developed acute myocardial infarction (AMI) complicated by extensive coronary thrombosis and cardiogenic shock. She underwent percutaneous coronary intervention and placement of a mechanical circulatory support device but subsequently died from shock. This report illustrates the challenges in managing patients with COVID‐19, AMI, and cardiogenic shock.


title: The cancellation of mass gatherings (MGs)? Decision making in the time of COVID-19

text: Abstract Our recommendation, as experts who have monitored health hazards at the Hajj for over 15 years, especially if the situation with COVID-19 continues to escalate globally is that Hajj 2020 will be at risk of being suspended and a means for Muslims to fulfill their rights in the future either personally or even by proxy need to be announced. The same holds true for the Summer 2020 Olympics in Japan and for many other MGs and large gatherings. Decisions in the time of COVID-19 will be closely followed and will be a blueprint for other mass gatherings.


title: Patient satisfaction with doctor–patient interaction in a radiotherapy centre during the severe acute respiratory syndrome outbreak

text: An outpatient radiotherapy department assessed how precautions implemented during the severe acute respiratory syndrome (SARS) outbreak affected patient satisfaction with doctor–patient interaction and explored variables potentially influencing satisfaction. The information obtained would help prepare us for future infectious disease outbreaks. Outpatients seen during the outbreak completed a validated questionnaire assessing satisfaction with doctor–patient interaction. Additional items assessed included patients’ perception of SARS measures and patient demographics. Of 149 patients, 97% had heard of SARS, 92% believed SARS precautions necessary, and 54% believed contracting SARS was possible despite the precautions. Patients were satisfied with doctors wearing masks (97%), temperature checks (97%), and patients wearing masks (96%). Despite the high satisfaction levels with SARS precautions, 24% believed it had adversely affected doctor–patient interaction. With regards to doctor–patient interaction, 94% of patients were satisfied. Patients were most satisfied with the ‘information exchange’ domain (mean score 3.23 out of 4) compared to other domains (P < 0.0001, 100.00% confidence) and were less satisfied with the ‘empathy’ domain compared to other domains (P < 0.0001, 100.00% confidence). Patients were most satisfied with understanding their treatment plan (100%), doctor being honest (97%) and being understood (96%). Patients were least satisfied with information about caring for their illness (61%), that the visit could be better (59%), and the doctor showing more interest (58%). On multivariate analysis, patients who were less satisfied with SARS measures were significantly less satisfied with doctor–patient interaction (P = 0.0001). Dissatisfaction with SARS measures was associated with significant dissatisfaction for questions in all domains. Older age and non‐breast cancer patients were also less satisfied with doctor–patient interaction. Most (94%) of patients were satisfied with doctor–patient interaction, despite implementation of infectious disease prevention measures. However, patients who were dissatisfied with the SARS precautions had poorer satisfaction. In particular, physician empathy appeared to be most adversely affected. The results have relevance to any radiotherapy department preparing contingency plans in the event of infectious disease outbreaks.


title: Detection of novel respiratory viruses from influenza‐like illness in the Philippines

text: Several novel viruses have been recently identified in respiratory samples. However, the epidemiology of these viruses in tropical countries remains unclear. The aim of the present study was to provide an overview of the epidemiology of novel respiratory viruses, including human metapneumovirus, human bocavirus, new subtypes of human coronavirus (NL63 and HKU1), KI virus, WU virus, and Melaka virus in the Philippines, a tropical country. Nasopharyngeal aspirates from 465 patients with influenza‐like illness were collected in 2006 and 2007. Reverse transcription polymerase chain reaction (RT‐PCR) and PCR were performed to detect viruses from culture‐negative specimens. Human metapneumovirus, human bocavirus, human coronavirus HKU1, KI virus, and WU virus were detected for the first time in the Philippines; Melaka virus was not found. J. Med. Virol. 82:1071–1074, 2010. © 2010 Wiley‐Liss, Inc.


title: Comparative Analysis of Eleven Healthcare-Associated Outbreaks of Middle East Respiratory Syndrome Coronavirus (Mers-Cov) from 2015 to 2017

text: Since its emergence in 2012, 2,260 cases and 803 deaths due to Middle East respiratory syndrome coronavirus (MERS-CoV) have been reported to the World Health Organization. Most cases were due to transmission in healthcare settings, sometimes causing large outbreaks. We analyzed epidemiologic and clinical data of laboratory-confirmed MERS-CoV cases from eleven healthcare-associated outbreaks in the Kingdom of Saudi Arabia and the Republic of Korea between 2015–2017. We quantified key epidemiological differences between outbreaks. Twenty-five percent (n = 105/422) of MERS cases who acquired infection in a hospital setting were healthcare personnel. In multivariate analyses, age ≥65 (OR 4.8, 95%CI: 2.6–8.7) and the presence of underlying comorbidities (OR: 2.7, 95% CI: 1.3–5.7) were associated with increased mortality whereas working as healthcare personnel was protective (OR 0.07, 95% CI: 0.01–0.34). At the start of these outbreaks, the reproduction number ranged from 1.0 to 5.7; it dropped below 1 within 2 to 6 weeks. This study provides a comprehensive characterization of MERS HCA-outbreaks. Our results highlight heterogeneities in the epidemiological profile of healthcare-associated outbreaks. The limitations of our study stress the urgent need for standardized data collection for high-threat respiratory pathogens, such as MERS-CoV.


title: Spike Protein Fusion Peptide and Feline Coronavirus Virulence

text: Coronaviruses are well known for their potential to change their host or tissue tropism, resulting in unpredictable new diseases and changes in pathogenicity; severe acute respiratory syndrome and feline coronaviruses, respectively, are the most recognized examples. Feline coronaviruses occur as 2 pathotypes: nonvirulent feline enteric coronaviruses (FECVs), which replicate in intestinal epithelium cells, and lethal feline infectious peritonitis viruses (FIPVs), which replicate in macrophages. Evidence indicates that FIPV originates from FECV by mutation, but consistent distinguishing differences have not been established. We sequenced the full genome of 11 viruses of each pathotype and then focused on the single most distinctive site by additionally sequencing hundreds of viruses in that region. As a result, we identified 2 alternative amino acid differences in the putative fusion peptide of the spike protein that together distinguish FIPV from FECV in >95% of cases. By these and perhaps other mutations, the virus apparently acquires its macrophage tropism and spreads systemically.


First reported in September 2012, the Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV) has resulted in 206 laboratory-confirmed deaths, with a 42% mortality rate as of 27 March 2014. Closely related coronaviruses have been isolated in bats, but most evidence suggests that humans have become infected directly from camels in a number of separate transmission events, with limited human-to-human transmission reported thus far. The majority of cases originated in the Middle East (predominantly Saudi Arabia), including all the index cases. Clinical manifestations primarily involve fever, chills, and rapidly progressive respiratory failure, often resulting in an acute respiratory distress syndrome, with a minority of patients reporting gastrointestinal symptoms, as well. The majority of critically ill patients are older males with medical co-morbidities, and a large number of minimally symptomatic cases likely go undetected. Unfortunately, attempted therapies have all been unsuccessful thus far, and treatment remains supportive care.


SARS‐CoV‐2 and HIV


title: Robust Atomistic Modeling of Materials, Organometallic, and Biochemical Systems

text: Modern chemistry seems to be unlimited in molecular size and elemental composition. Metal‐organic frameworks or biological macromolecules involve complex architectures and a large variety of elements. Yet, a general and broadly applicable theoretical method to describe the structures and interactions of molecules beyond the 1000‐atom size regime semi‐quantitatively is not self‐evident. For this purpose, a generic force field named GFN‐FF is presented, which is completely newly developed to enable fast structure optimizations and molecular‐dynamics simulations for basically any chemical structure consisting of elements up to radon. The freely available computer program requires only starting coordinates and elemental composition as input from which, fully automatically, all potential‐energy terms are constructed. GFN‐FF outperforms other force fields in terms of generality and accuracy, approaching the performance of much more elaborate quantum‐mechanical methods in many cases.


Can COVID 19 virus be transmitted through sex?


Challenges in the management of critical ill COVID‐19 patients with pressure ulcer


Intragenic variations in the HCMV RL11-family


In Reply–The “Perfect Cytokine Storm” of COVID-19


title: Increased replication of respiratory syncytial virus in the presence of cytokeratin 8 and 18

text: Previously, it was reported that productive viral infection, viral protein synthesis, and viral RNA replication of respiratory syncytial virus (RSV) operated efficiently in two human epithelial cell lines (HEp‐2 and A549), but not in a human mast‐cell line, HMC‐1. Based on these observations, it was hypothesized that HMC‐1 cells lack the machinery required for RSV replication. To identify the host factors required for RSV replication, cDNA subtraction using A549, HEp‐2, and HMC‐1 cells was performed, and cytokeratin 18 (C18) was identified as a candidate host factor. Because C18 is generally expressed in simple epithelia with cytokeratin 8 (C8), HMC‐1 cells that constitutively express C18 and C8 (HMC‐1‐C8/18) were established to evaluate the role of C8/18 in RSV replication. In HMC‐1‐C8/18 cells, RSV RNA replication was increased, and the amount of infective virus produced was also increased in the cellular fraction after RSV spinoculation, whereas RSV production was decreased in A549 cells in which C18 expression was knocked down. These data suggest that the replication of RSV increases in the presence of C8/18. J. Med. Virol. 84:365–370, 2012. © 2011 Wiley Periodicals, Inc.


title: Any port in a storm: Cryptocurrency safe-havens during the COVID-19 pandemic

text: Controlling for the polarity and subjectivity of social media data based on the development of the COVID-19 outbreak, we analyse the relationships between the largest cryptocurrencies and such time-varying realisation as to the scale of the economic shock centralised within the rapidly-escalating pandemic. We find evidence of significant growth in both returns and volumes traded, indicating that large cryptocurrencies acted as a store of value during this period of exceptional financial market stress. Further, cryptocurrency returns are found to be significantly influenced by negative sentiment relating to COVID-19. While not only providing diversification benefits for investors, results suggest that these digital assets acted as a safe-haven similar to that of precious metals during historic crises.


title: Food Safety: Emerging Pathogens

text: Abstract This article presents information related to emerging pathogens that are foodborne or have the potential to be foodborne including bacteria, viruses, and parasites. The phenotypic characteristics of these pathogens, their epidemiology, prevalence in foods, and transmission routes to humans as well as means for their control are also discussed.


title: Ganglioside Biochemistry

text: Gangliosides are sialic acid-containing glycosphingolipids. They occur especially on the cellular surfaces of neuronal cells, where they form a complex pattern, but are also found in many other cell types. The paper provides a general overview on their structures, occurrence, and metabolism. Key functional, biochemical, and pathobiochemical aspects are summarized.


Recombinant human ACE2: acing out angiotensin II in ARDS therapy


title: Surveillance and Testing for Middle East Respiratory Syndrome Coronavirus, Saudi Arabia, April 2015–February 2016

text: Saudi Arabia has reported >80% of the Middle East respiratory syndrome coronavirus (MERS-CoV) cases worldwide. During April 2015–February 2016, Saudi Arabia identified and tested 57,363 persons (18.4/10,000 residents) with suspected MERS-CoV infection; 384 (0.7%) tested positive. Robust, extensive, and timely surveillance is critical for limiting virus transmission.


docid: vyidtnnq

title: Coinfection modulates inflammatory responses, clinical outcome and pathogen load of H1N1 swine influenza virus and Haemophilus parasuis infections in pigs

text: BACKGROUND: Respiratory co-infections are important factor affecting the profitability of pigs production. Swine influenza virus (SIV) may predispose to secondary infection. Haemophilus parasuis (Hps) can be a primary pathogen or be associated with other pathogens such as SIV. To date, little is known about the effect of coinfection with SIV and Hps on the disease severity and inflammatory response and the role of Hps in the induction of pneumonia in the absence of other respiratory pathogens. In the study we investigated the influence of SIV and Hps coinfection on clinical course, inflammatory response, pathogens shedding and load at various time points following intranasal inoculation. The correlation between local concentration of cytokines and severity of disease as well as serum acute phase proteins (APP) concentration has been also studied. RESULTS: All co-infected pigs had fever, while in single inoculated pigs fever was observed only in part of animals. Necropsy revealed lesions in the lungs all SIV-inoculated and co-inoculated pigs, while in Hps-single inoculated animals only 1 out of 11 pigs revealed gross lung lesions. The SIV shedding was the highest in co-inoculated pigs. There were no differences between Hps-single inoculated and co-inoculated groups with regard to Hps shedding. The significant increase in Hps titre in the lung has been found only in co-inoculated group. All APP increased after co-infection. In single-inoculated animals various kinetics of APP response has been observed. The lung concentrations of cytokines were induced mostly in SIV + Hps pigs in the apical and middle lobe. These results correlated well with localization of gross lung lesions. CONCLUSIONS: The results revealed that SIV increased the severity of lung lesions and facilitated Hps (PIWetHps192/2015) replication in the porcine lung. Furthermore, Hps influenced the SIV nasal shedding. Enhanced Hps and SIV replication, together with stronger systemic and local inflammatory response contributed to a more severe clinical signs and stronger, earlier immune response in co-inoculated animals. We confirmed the previous evidence that single-Hps infection does not produce significant pneumonic lesions but it should be in mind that other strains of Hps may produce lesions different from that reported in the present study.


title: Genomic Analyses of Human European Diversity at the Southwestern Edge: Isolation, African Influence and Disease Associations in the Canary Islands

text: Despite the genetic resemblance of Canary Islanders to other southern European populations, their geographical isolation and the historical admixture of aborigines (from North Africa) with sub-Saharan Africans and Europeans have shaped a distinctive genetic makeup that likely affects disease susceptibility and health disparities. Based on single nucleotide polymorphism array data and whole genome sequencing (30×), we inferred that the last African admixture took place ∼14 generations ago and estimated that up to 34% of the Canary Islander genome is of recent African descent. The length of regions in homozygosis and the ancestry-related mosaic organization of the Canary Islander genome support the view that isolation has been strongest on the two smallest islands. Furthermore, several genomic regions showed significant and large deviations in African or European ancestry and were significantly enriched in genes involved in prevalent diseases in this community, such as diabetes, asthma, and allergy. The most prominent of these regions were located near LCT and the HLA, two well-known targets of selection, at which 40‒50% of the Canarian genome is of recent African descent according to our estimates. Putative selective signals were also identified in these regions near the SLC6A11-SLC6A1, KCNMB2, and PCDH20-PCDH9 genes. Taken together, our findings provide solid evidence of a significant recent African admixture, population isolation, and adaptation in this part of Europe, with the favoring of African alleles in some chromosome regions. These findings may have medical implications for populations of recent African ancestry.


title: A systematic review and meta-analysis of cancer patients affected by a novel coronavirus

text: BACKGROUND: Cancer patients with COVID-19 disease have been reported to have double the case fatality rate of the general population. MATERIALS AND METHODS: A systematic search of PubMed/MEDLINE, Embase, Cochrane Central, Google Scholar, and MedRxiv was done for studies on cancer patients with COVID-19. Pooled proportions were calculated for categorical variables. Odds ratio and forest plots were constructed for both primary and secondary outcomes. The random-effects model was used to account for heterogeneity between studies. RESULTS: This systematic review of 31 studies and meta-analysis of 181,323 patients from 26 studies involving 23,736 cancer patients is the largest meta-analysis to the best of our knowledge assessing outcomes in cancer patients affected by COVID-19. Our meta-analysis shows that cancer patients with COVID-19 have a higher likelihood of death (odds ratio, OR 2.54), which was largely driven by mortality among patients in China. Cancer patients were more likely to be intubated, although ICU admission rates were not statistically significant. Among cancer subtypes, the mortality was highest in hematological malignancies (OR 2.43) followed by lung cancer (OR 1.8). There was no association between receipt of a particular type of oncologic therapy and mortality. Our study showed that cancer patients affected by COVID-19 are a decade older than the normal population and have a higher proportion of co-morbidities. There was insufficient data to assess the association of COVID-directed therapy and survival outcomes in cancer patients. Despite the heterogeneity of studies and inconsistencies in reported variables and outcomes, these data could guide clinical practice and oncologic care during this unprecedented global health pandemic. CONCLUSION: Cancer patients with COVID-19 disease are at increased risk of mortality and morbidity. A more nuanced understanding of the interaction between cancer-directed therapies and COVID-19-directed therapies is needed. This will require uniform prospective recording of data, possibly in multi-institutional registry databases.


title: A Human Rights Approach to Emergency Response? The Advocacy of Canada's Human Rights Commissions during the COVID-19 Crisis

text: Emergencies can threaten human rights by disrupting societies, increasing vulnerabilities, and instigating exceptional measures from governments and other actors. As independent institutions mandated to protect and promote the human rights embedded in Canada's federal, provincial and territorial legislation, Canada's human rights commissions (HRCs) have mobilized to advocate for human rights during the COVID-19 public health emergency.


title: Disruption of Arthroplasty Practice in an Orthopedic Center in Northern Italy During the Coronavirus Disease 2019 Pandemic

text: Abstract Background The Coronavirus disease 2019 (COVID-19) outbreak has put a strain on many healthcare systems around the world, with important consequences. The aim of this paper is to describe the impact of the COVID-19 pandemic on hip and knee arthroplasties in an Italian high-volume orthopedic center, located in the region of the country first and worst affected by the Coronavirus. Methods Data from institutional database were retrospectively analyzed to obtain the number of hip and knee arthroplasties performed from February 24 to April 10 2020. The figures were compared with those of the same 7-week period of the last year (2019). Results The number of hip and knee arthroplasties showed a decrease from 706 in the same period of 2019 to 166 (76.5% less) in the current year. In 2019, a mean of 101 ± 9 hip and knee arthroplasties were performed per week compared with a mean of 24 ± 34 in 2020. Ten patients were tested positive for SARS-CoV2 during hospital stay. Two of these patients died after a regular postoperative period after developing unexpectedly COVID-19 during rehabilitation. The mortality in the 7-week period of the current year was 1.2% compared with 0% in 2019. Conclusion The outbreak of COVID-19 had a considerable effect in our center on the number of hip and knee arthroplasties that rapidly decreased to 0 in parallel to the worsening of the situation in the country. Efforts will be soon requested because our practice is going to deal with the after-effects of the pandemic in the near future.


title: Perceived vulnerability to disease and attitudes towards public health measures: COVID-19 in Flanders, Belgium

text: During the COVID-19 pandemic, governments installed measures to contain the disease. Information about these measures was disseminated through news media. Nonetheless, many individuals did not abide by these guidelines. We investigated how perceived vulnerability to disease and personality characteristics related to support for public health measures. We analyzed survey data of 1000 Flemish (Belgium) adults, collected between March 17, 2020 and March 22, 2020. Older age, low educational attainment, gender (female) and work situation (no telecommuting) were associated with greater perceived vulnerability. Greater expectations of loneliness and more solidarity with our fellow men were associated with gender (female), younger age and work situation (telecommuting). Greater perceived vulnerability to disease was related to a greater belief that public health measures protect the population, but also to a critical stance towards the Belgian government's handling of the crisis. High agreeableness and high emotional stability were associated with respectively greater belief that health measures protect the population, and greater support for the government's crisis management. Watching television news was related to a greater belief that public health measures are necessary, and specifically consuming public television news increased support for public health measures. We discuss the implications for handling the COVID-19 pandemic.


title: The electronic medical record and COVID-19: is it up to the challenge?

text: • Improvements to the electronic medical records must occur prior to the next pandemic; • During pandemics, infection preventionists’ should advise staff, not review charts; • Automation can help improve healthcare safety and quality;


docid: nnedgexs

title: Antiviral Activity of Novel Quinoline Derivatives against Dengue Virus Serotype 2

text: Dengue virus causes dengue fever, a debilitating disease with an increasing incidence in many tropical and subtropical territories. So far, there are no effective antivirals licensed to treat this virus. Here we describe the synthesis and antiviral activity evaluation of two compounds based on the quinoline scaffold, which has shown potential for the development of molecules with various biological activities. Two of the tested compounds showed dose-dependent inhibition of dengue virus serotype 2 in the low and sub micromolar range. The compounds 1 and 2 were also able to impair the accumulation of the viral envelope glycoprotein in infected cells, while showing no sign of direct virucidal activity and acting possibly through a mechanism involving the early stages of the infection. The results are congruent with previously reported data showing the potential of quinoline derivatives as a promising scaffold for the development of new antivirals against this important virus.


title: Emerging henipaviruses and flying foxes – Conservation and management perspectives

text: Abstract Wildlife populations are affected by a series of emerging diseases, some of which pose a significant threat to their conservation. They can also be reservoirs of pathogens that threaten domestic animal and human health. In this paper, we review the ecology of two viruses that have caused significant disease in domestic animals and humans and are carried by wild fruit bats in Asia and Australia. The first, Hendra virus, has caused disease in horses and/or humans in Australia every five years since it first emerged in 1994. Nipah virus has caused a major outbreak of disease in pigs and humans in Malaysia in the late 1990s and has also caused human mortalities in Bangladesh annually since 2001. Increased knowledge of fruit bat population dynamics and disease ecology will help improve our understanding of processes driving the emergence of diseases from bats. For this, a transdisciplinary approach is required to develop appropriate host management strategies that both maximise the conservation of bat populations as well as minimise the risk of disease outbreaks in domestic animals and humans.


title: Virus replicon particles expressing porcine reproductive and respiratory syndrome virus proteins elicit immune priming but do not confer protection from viremia in pigs

text: Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent of one of the most devastating and economically significant viral disease of pigs worldwide. The vaccines currently available on the market elicit only limited protection. Recombinant vesicular stomatitis virus (VSV) replicon particles (VRP) have been used successfully to induce protection against influenza A virus (IAV) in chickens and bluetongue virus in sheep. In this study, VSV VRP expressing the PRRSV envelope proteins GP5, M, GP4, GP3, GP2 and the nucleocapsid protein N, individually or in combination, were generated and evaluated as a potential vector vaccine against PRRSV infection. High level expression of the recombinant PRRSV proteins was demonstrated in cell culture. However, none of the PRRSV antigens expressed from VRP, with the exception of the N protein, did induce any detectable antibody response in pigs before challenge infection with PRRSV. After challenge however, the antibody responses against GP5, GP4 and GP3 appeared in average 2 weeks earlier than in pigs vaccinated with the empty control VRP. No reduction of viremia was observed in the vaccinated group compared with the control group. When pigs were co-vaccinated with VRP expressing IAV antigens and VRP expressing PRRSV glycoproteins, only antibody responses to the IAV antigens were detectable. These data show that the VSV replicon vector can induce immune responses to heterologous proteins in pigs, but that the PRRSV envelope proteins expressed from VSV VRP are poorly immunogenic. Nevertheless, they prime the immune system for significantly earlier B-cell responses following PRRSV challenge infection.


title: Bacillus Calmette–Guérin vaccination and clinical characteristics and outcomes of COVID-19 in Rhode Island, United States: a cohort study

text: Coronavirus disease 2019 (COVID-19) has resulted in a global pandemic, and there is limited data on effective therapies. Bacillus Calmette–Guérin (BCG) vaccine, a live-attenuated strain derived from an isolate of Mycobacterium bovis and originally designed to prevent tuberculosis, has shown some efficacy against infection with unrelated pathogens. In this study, we reviewed 120 consecutive adult patients (≥18 years old) with COVID-19 at a major federally qualified health centre in Rhode Island, United States from 19 March to 29 April 2020. Median age was 39.5 years (interquartile range, 27.0–50.0), 30% were male and 87.5% were Latino/Hispanics. Eighty-two (68.3%) patients had BCG vaccination. Individuals with BCG vaccination were less likely to require hospital admission during the disease course (3.7% vs. 15.8%, P = 0.019). This association remained unchanged after adjusting for demographics and comorbidities (P = 0.017) using multivariate regression analysis. The finding from our study suggests the potential of BCG in preventing more severe COVID-19.


title: COVID-19 and diabetes: The why, the what and the how

text: BACKGROUND: The novel coronavirus SARS-CoV-2 has taken the world by storm. Alongside COVID-19, diabetes is a long-standing global epidemic. The diabetes population has been reported to suffer adverse outcomes if infected by COVID-19. The aim was to summarise information and resources available on diabetes and COVID-19, highlighting special measures that individuals with diabetes need to follow. METHODS: A search using keywords “COVID-19” and “Diabetes” was performed using different sources, including PubMed and World Health Organization. RESULTS: COVID-19 may enhance complications in individuals with diabetes through an imbalance in angiotension-converting enzyme 2 (ACE2) activation pathways leading to an inflammatory response. ACE2 imbalance in the pancreas causes acute β-cell dysfunction and a resultant hyperglycemic state. These individuals may be prone to worsened COVID-19 complications including vasculopathy, coagulopathy as well as psychological stress. Apart from general preventive measures, remaining hydrated, monitoring blood glucose regularly and monitoring ketone bodies in urine if on insulin is essential. All this while concurrently maintaining physical activity and a healthy diet. Different supporting entities are being set up to help this population. CONCLUSION: COVID-19 is a top priority. It is important to remember that a substantial proportion of the world's population is affected by other co-morbidities such as diabetes. These require special attention during this pandemic to avoid adding on to the burden of countries' healthcare systems.


title: Control of HPV-associated tumors by innovative therapeutic HPV DNA vaccine in the absence of CD4+ T cells

text: Human papillomavirus (HPV) infections are particularly problematic for HIV + and solid organ transplant patients with compromised CD4+ T cell-dependent immunity as they produce more severe and progressive disease compared to healthy individuals. There are no specific treatments for chronic HPV infection, resulting in an urgent unmet need for a modality that is safe and effective for both immunocompromised and otherwise normal patients with recalcitrant disease. DNA vaccination is attractive because it avoids the risks of administration of live vectors to immunocompromised patients, and can induce potent HPV-specific cytotoxic T cell responses. We have developed a DNA vaccine (pNGVL4a-hCRTE6E7L2) encoding calreticulin (CRT) fused to E6, E7 and L2 proteins of HPV-16, the genotype associated with approximately 90% vaginal, vulvar, anal, penile and oropharyngeal HPV-associated cancers and the majority of cervical cancers. Administration of the DNA vaccine by intramuscular (IM) injection followed by electroporation induced significantly greater HPV-specific immune responses compared to IM injection alone or mixed with alum. Furthermore, pNGVL4a-hCRTE6E7L2 DNA vaccination via electroporation of mice carrying an intravaginal HPV-16 E6/E7-expressing syngeneic tumor demonstrated more potent therapeutic effects than IM vaccination alone. Of note, administration of the DNA vaccine by IM injection followed by electroporation elicited potent E6 and E7-specific CD8+ T cell responses and antitumor effects despite CD4+ T cell-depletion, although no antibody response was detected. While CD4+ T cell-depletion did reduce the E6 and E7-specific CD8+ T cell response, it remained sufficient to prevent subcutaneous tumor growth and to eliminate circulating tumor cells in a model of metastatic HPV-16+ cancer. Thus, the antibody response was CD4-dependent, whereas CD4+ T cell help enhanced the E6/E7-specific CD8+ T cell immunity, but was not required. Taken together, our data suggest that pNGVL4a-hCRTE6E7L2 DNA vaccination via electroporation warrants testing in otherwise healthy patients and those with compromised CD4+ T cell immunity to treat HPV-16-associated anogenital disease and cancer.


title: Lung epithelial cells have virus-specific and shared gene expression responses to infection by diverse respiratory viruses

text: The severity of respiratory viral infections is partially determined by the cellular response mounted by infected lung epithelial cells. Disease prevention and treatment is dependent on our understanding of the shared and unique responses elicited by diverse viruses, yet few studies compare host responses to viruses from different families while controlling other experimental parameters. Murine models are commonly used to study the pathogenesis of respiratory viral infections, and in vitro studies using murine cells provide mechanistic insight into the pathogenesis observed in vivo. We used microarray analysis to compare changes in gene expression of murine lung epithelial cells infected individually by three respiratory viruses causing mild (rhinovirus, RV1B), moderate (coronavirus, MHV-1), and severe (influenza A virus, PR8) disease in mice. RV1B infection caused numerous gene expression changes, but the differential effect peaked at 12 hours post-infection. PR8 altered an intermediate number of genes whose expression continued to change through 24 hours. MHV-1 had comparatively few effects on host gene expression. The viruses elicited highly overlapping responses in antiviral genes, though MHV-1 induced a lower type I interferon response than the other two viruses. Signature genes were identified for each virus and included host defense genes for PR8, tissue remodeling genes for RV1B, and transcription factors for MHV-1. Our comparative approach identified universal and specific transcriptional signatures of virus infection that can be used to distinguish shared and virus-specific mechanisms of pathogenesis in the respiratory tract.


title: Prevalence of respiratory virus in symptomatic children in private physician office settings in five communities of the state of Veracruz, Mexico

text: BACKGROUND: Acute respiratory tract infections are the leading cause of morbidity and mortality in children worldwide. Many studies have described the frequency of viruses in hospitalized patients, but studies describing the prevalence of viruses in the community setting are limited, particularly in developing countries, where most of the deaths from serious respiratory diseases occur. The aim of this study was to evaluate the diversity of respiratory viruses in the community setting using molecular diagnostic tools, as well as the clinical characteristics of respiratory viral infections in the general pediatric practice in Mexico. METHODS: Children with respiratory tract infections attending private pediatric practices during a 10-month period in five cities of the state of Veracruz were included. Nasal swabs were taken and processed by a multiplex detection kit for 15 respiratory viruses. RESULTS: 525 children were included from July 2011 to May 2012; 44% were female, mean age was 45 months. The 3 most frequent clinical diagnosis were: rhinopharyngitis 68%, pharyngitis 18%, and 3.3% influenza-like illness. 71.5% of the samples were positive for virus. The five most frequent pathogens were respiratory syncycitial virus in 18.3% of the children, rhinovirus in 17.5%, influenza A 9.1%, adenovirus 7.2%, and enterovirus 3.4%, although all 15 viruses were detected; there were viral coinfections in 14.1%, and 28.5% of the samples were negative. CONCLUSIONS: A large proportion of respiratory infections in the community setting in Mexico was associated to viruses. Although testing for common respiratory pathogens in children with acute respiratory tract infections may lead to a better understanding of the role of viral pathogens in, and eventually to improvement in the management of, individual patients, additional prospective studies are required to study the need of routinely using such tests in general pediatric practices in resource-limited countries.


title: Toward development of generic inhibitors against the 3C proteases of picornaviruses

text: Development of novel antivirals, which requires knowledge of the viral life cycle in molecular detail, is a daunting task, involving extensive investments, and frequently resulting in failure. As there exist significant commonalities among virus families in the manner of host interaction, identifying and targeting common rather than specific features may lead to the development of broadly useful antivirals. Here, we have targeted the 3C protease of Hepatitis A Virus (HAV), a feco‐orally transmitted virus of the family Picornaviridae, for identification of potential antivirals. The 3C protease is a viable drug target as it is required by HAV, as well as by other picornaviruses, for post‐translational proteolysis of viral polyproteins and for inhibiting host innate immune pathways. Computational screening, followed by chemical synthesis and experimental validation resulted in identification of a few compounds which, at low micromolar concentrations, could inhibit HAV 3C activity. These compounds were further tested experimentally against the 3C protease of Human Rhinovirus, another member of the Picornaviridae family, with comparable results. Computational studies on 3C proteases from other members of the picornavirus family have indicated that the compounds identified could potentially be generic inhibitors for picornavirus 3C proteases.


title: Effective strategies for responding to rumors about risks: The case of radiation-contaminated food in South Korea

text: Abstract This experimental study explores how governments should respond to rumors about national-level risk issues. Informed by research in rumor psychology and risk/crisis communication, it investigates whether type of rumor and rumor response strategy have main and interaction effects on reducing rumor beliefs and intention to disseminate rumor. The two featured rumor types are the bogie rumor, which highlights feared outcomes, and the wedge rumor, which aims to reinforce differences between rival groups. Derived from Situational Crisis Communication Theory, the three response strategies examined are refuting the rumor, denying it, and attacking its source. Data were drawn from part of a large-scale online experiment, and the sample of the analysis was 942 South Korean adults. The experiment had a between-subjects design of 2 rumor type (wedge vs. bogie) x 3 government response strategies (refutation, denial, attack the attacker). Results show that all three rumor response strategies significantly reduced rumor beliefs, but only the refutation strategy significantly reduced intention to disseminate the rumor. Rumor type (bogie) and response strategies (refutation) had main, but not interaction, effects on reduction of intention to disseminate the rumor.


docid: kjgpriow

title: Quercetin solid lipid microparticles: A flavonoid for inhalation lung delivery

text: Abstract Purpose The aim of the present work was to develop solid lipid microparticles (SLMs), as dry powders containing quercetin for direct administration to the lung. Methods Quercetin microparticles were prepared by o/w emulsification via a phase inversion technique, using tristearin as the lipid component and phosphatidylcholine as an emulsifier. The quercetin SLMs were characterised for morphology, drug loading (15.5%±0.6, which corresponded to an encapsulation efficiency of 71.4%), particle size distribution, response to humidity, crystallinity, thermal behaviour and in vitro respirable fraction. Furthermore, the toxicity and the in vitro transport of the SLMs on an air liquid interface model of the Calu-3 cell line were also investigated using a modified twin-stage impinger apparatus. Results Results showed that quercetin SLMs could be formulated as dry powder suitable for inhalation drug delivery (20.5±3.3% fine particle fraction ⩽4.46μm) that was absorbed, via a linear kinetic model across the Calu-3 monolayer (22.32±1.51% over 4h). In addition, quercetin SLMs were shown to be non-toxic at the concentrations investigated. Interestingly, no apical to basolateral transport of the micronised quercetin was observed over the period of study. Conclusions These observations suggest quercetin diffusion was enhanced by the presence of the lipid/emulsifying excipients in the SLMs; however further studies are necessary to elucidate the exact mechanisms.


title: Enterotropic Strains of Mouse Coronavirus Differ in Their Use of Murine Carcinoembryonic Antigen-Related Glycoprotein Receptors

text: Abstract Enterotropic mouse hepatitis virus strains (MHV-RI and MHV-Y) replicate in the intestine and rarely disseminate to other tissues, unlike respiratory MHV strains. Murine carcinoembryonic antigen-related glycoproteins (MHVR and mmCGM2) are expressed in many murine tissues and serve as receptors for respiratory MHV strains. To assess the role of receptors in the limited tissue tropism of enterotropic MHV strains, the permissiveness of MHVR- and mmCGM2-expressing cell lines and peritoneal exudate cells from BALB/c and SJL mice for MHV-RI and MHV-Y replication was determined. MHVR transfected BHK cells were susceptible to infection with both MHV-RI and MHV-Y. Additionally, the anti-MHVR monoclonal antibody CC1 blocked MHV-RI and MHV-Y infection. mmCGM2-transfected BHK cells were susceptible to infection with MHV-Y, but not MHV-RI. Peritoneal exudate cells from BALB/c mice were susceptible to infection with MHV-Y and MHVRI, whereas peritoneal exudate cells from SJL- mice were susceptible to infection with MHV-Y but not MHV-RI. These results indicate that MHV-RI probably uses a different receptor than other MHV strains to infect SJL mice and that receptors are probably not the primary determinant of the limited tissue tropism of enterotropic MHV strains.


title: French consensus regarding precautions during tracheostomy and post-tracheostomy care in the context of COVID-19 pandemic

text: Abstract Tracheostomy post-tracheostomy care are regarded as at high risk for contamination of health care professionals with the new coronavirus (SARS-CoV-2). Considering the rapid spread of the infection, all patients in France must be considered as potentially infected by the virus. Nevertheless, patients without clinical or radiological (CT scan) markers of COVID-19, and with negative nasopharyngeal sample within 24h of surgery, are at low risk of being infected. Instructions for personal protection include specific wound dressings and decontamination of all material used. The operating room should be ventilated after each tracheostomy and the pressure of the room should be neutral or negative. Percutaneous tracheostomy is to be preferred over surgical cervicotomy in order to reduce aerosolization and to avoid moving patients from the intensive care unit to the operating room. Ventilation must be optimized during the procedure, to limit patient oxygen desaturation. Drug assisted neuromuscular blockage is advised to reduce coughing during tracheostomy tube insertion. An experienced team is mandatory to secure and accelerate the procedure as well as to reduce risk of contamination.


title: How should colorectal surgeons practice during the COVID‐19 epidemic? A retrospective single‐center analysis based on real‐world data from China

text: BACKGROUND: The coronavirus disease 2019 is currently of global concern. Cancer patients are advised to stay at home in case of potential infection, which may cause delays of routine diagnosis and necessary treatment. How colorectal surgeons should manage this during the epidemic remains a big challenge. OBJECTIVE: To evaluate the feasibility of routine colorectal surgery during coronavirus disease 2019 and to offer some Chinese recommendations to colorectal surgeons throughout the world. METHODS: A total of 166 patients receiving colorectal surgery from 20th December 2019 to 20th March 2020 at Department of General Surgery in Chinese General Hospital of People's Liberation Army were enrolled, and further divided into two groups based on before or after admission date of 20th January 2020. Clinicopathologic data such as hospital stay and economic data such as total costs were collected and analyzed retrospectively. RESULTS: Longer hospital stay, higher proportion of non‐local patients and more hospitalization cost were found in the post‐20 January group (special‐time group) (P < 0.001; P < 0.05; P < 0.05 respectively). Apart from this, no difference existed with regard to baseline demographical data such as age, sex and height, as well as clinicopathological data such as previous history, surgery time, operation extent and TNM staging. CONCLUSIONS: This real‐world study indicated that performing colorectal surgery during coronavirus disease 2019 epidemic might be safe and feasible based on comprehensive screening and investigation. We have summarized several recommendations here, hoping to help surgeons from related departments across the world. This article is protected by copyright. All rights reserved.


title: Beyond Respiratory Syncytial Virus and Rhinovirus in the Pathogenesis and Exacerbation of Asthma The Role of Metapneumovirus, Bocavirus and Influenza Virus

text: Respiratory viruses other than rhinovirus or respiratory syncytial virus, including human metapneumovirus, influenza virus, and human bocavirus, are important pathogens in acute wheezing illness and asthma exacerbations in young children. Whether infection with these viruses in early life is associated with recurrent wheezing and/or asthma is not fully investigated, although there are data to suggest children with human metapneumovirus lower respiratory tract infection may have a higher likelihood of subsequent and recurrent wheezing several years after initial infection.


title: International tracking of the COVID-19 invasion: an amazing example of a globalized scientific coordination effort

text: It is extraordinary to witness the spread of COVID-19 almost in real-time. This tight monitoring of the invasion of a new virus is a situation that most other invasion scientists could only dream of. Especially spatiotemporal spread data of the early phases of an invasion would be extremely useful in order to understand and predict the human-mediated spread of species around the globe. So far, invasive species that directly affect human health, such as the Sars-Cov-2 virus causing COVID-19, have been treated differently from invasive species affecting environmental health. Despite progresses in constructing large checklists of invasive species, these records often enter the databases only decades after the establishment of the organism in a country. This is inadequate to understand ongoing spread dynamics and estimate current invasion risks. Yet, national services often possess extremely useful information about early detections and interceptions of species at air and maritime ports, which could greatly improve predictions and help set management priorities. Considering the massive impacts of invasive species, it is time to move on to such a collaborative way of handling invasion data. Invasive insects, birds, mammals, fungi, and other species are the result of globalization and call for a globalized response, exactly like the COVID-19 pandemic.


title: ACE2 in Brain Physiology and Pathophysiology: Evidence from Transgenic Animal Models

text: Angiotensin-converting enzyme 2 (ACE2) is a protein consisting of two domains, the N-terminus is a carboxypeptidase homologous to ACE and the C-terminus is homologous to collectrin and responsible for the trafficking of the neutral amino acid transporter B(0)AT1 to the plasma membrane of gut epithelial cells. The carboxypeptidase domain not only metabolizes angiotensin II to angiotensin-(1–7), but also other peptide substrates, such as apelin, kinins and morphins. In addition, the collectrin domain regulates the levels of some amino acids in the blood, in particular of tryptophan. Therefore it is of no surprise that animals with genetic alterations in the expression of ACE2 develop a diverse pattern of phenotypes ranging from hypertension, metabolic and behavioural dysfunctions, to impairments in serotonin synthesis and neurogenesis. This review summarizes the phenotypes of such animals with a particular focus on the central nervous system.


title: A novel approach to the diagnosis and treatment of hemoptysis in infants: A case series

text: INTRODUCTION: Hemoptysis in children is an uncommon presenting symptom but can be life‐threatening if massive. Cardiac catheterization and coil embolization of aorto‐pulmonary collateral vessels (APCs) is uncommon in pediatric hemoptysis patients without congenital heart disease. METHODS: We present a series of seven infants (≤12 months of age) with hemoptysis, all of whom underwent cardiac catheterization to look for and intervene upon APCs, if found. Only those patients who underwent both bronchoscopy as well as cardiac catheterization from January 1995 to January 2015 were included in this retrospective review. RESULTS: Seven patients met inclusion criteria, and three had a history of recurrent hemoptysis. The mean age was 3 months. Four had evidence of bleeding on bronchoscopy. All seven had respiratory distress which necessitated ICU admission; five required mechanical ventilation. Cardiac catheterization showed significant APCs (>2 mm) in six of the seven studied patients, all of which were coil embolized. One patient had no significant APCs and therefore, no embolization. All patients had complete resolution with no recurrences during the 10‐20‐year outpatient follow‐up period. Chest CT scans were not helpful in delineating the site or etiology of bleeding in any patient. CONCLUSIONS: APCs should be considered as a differential diagnosis for pulmonary hemorrhage in infants after more common causes have been ruled out.


title: Recombinant vaccines against the mononegaviruses—What we have learned from animal disease controls

text: Abstract The mononegaviruses include a number of highly contagious and severe disease-causing viruses of both animals and humans. For the control of these viral diseases, development of vaccines, either with classical methods or with recombinant DNA virus vectors, has been attempted over the years. Recently reverse genetics of mononegaviruses has been developed and used to generate infectious viruses possessing genomes derived from cloned cDNA in order to study the consequent effects of viral gene manipulations on phenotype. This technology allows us to develop novel candidate vaccines. In particular, a variety of different attenuation strategies to produce a range of attenuated mononegavirus vaccines have been studied. In addition, because of their ideal nature as live vaccines, recombinant mononegaviruses expressing foreign proteins have also been produced with the aim of developing multivalent vaccines against more than one pathogen. These recombinant mononegaviruses are currently under evaluation as new viral vectors for vaccination. Reverse genetics could have great potential for the preparation of vaccines against many mononegaviruses.


title: A numerical method to determine the steady state distribution of passive contaminant in generic ventilation systems

text: Abstract Ventilation system with air recirculation is designed to conserve energy, yet at the same time may result in transporting hazardous substance among different rooms in the same building, which is a concern in indoor air quality control. There is a lack of effective methods to predict indoor contaminant distribution primarily because of uncertainty of the contaminant concentration in supply air which in turn due to the mixing ratio of fresh and recirculation air. In this paper, a versatile numerical method to determine the pollutant distribution of ventilation system with recirculation at steady state is proposed based on typical ventilation systems with accessibility of supply air (ASA) and accessibility of contaminant source (ACS). The relationship is established between contaminant concentrations of supply air and return air in a ventilated room or zone. The concentrations of supply air and contaminant distribution in each room can be determined using such parameters as ASA and ACS. The proposed method is validated by both experimental data and numerical simulation result. The computing speed of the proposed method is compared with the iteration method. The comparisons between the proposed method and the lumped parameter model are also conducted. The advantages of the proposed method in terms of accuracy, speed and versatility make it advantageous to be applied in air quality control of complex ventilation systems with recirculation.


title: Lymphoid chemokines in chronic neuroinflammation

text: Abstract Lymphoid chemokines play an essential role in the establishment and maintenance of lymphoid tissue microarchitecture and have been implicated in the formation of tertiary (or ectopic) lymphoid tissue in chronic inflammatory conditions. Here, we review recent advances in lymphoid chemokine research in central nervous system inflammation, focusing on multiple sclerosis and the animal model experimental autoimmune encephalomyelitis. We also highlight how the study of lymphoid chemokines, particularly CXCL13, has led to the identification of intrameningeal B-cell follicles in the multiple sclerosis brain paving the way to the discovery that these abnormal structures are highly enriched in Epstein–Barr virus-infected B cells and plasma cells.


title: Risk factors associated with exposure to bovine respiratory disease pathogens during the peri-weaning period in dairy bull calves

text: BACKGROUND: Bovine respiratory disease (BRD) remains among the leading causes of death of cattle internationally. The objective of this study was to identify risk factors associated with exposure to BRD pathogens during the peri-weaning period (day (d)-14 to d 14 relative to weaning at 0) in dairy bull calves using serological responses to these pathogens as surrogate markers of exposure. Clinically normal Holstein-Friesian and Jersey breed bull calves (n = 72) were group housed in 4 pens using a factorial design with calves of different breeds and planes of nutrition in each pen. Intrinsic, management and clinical data were collected during the pre-weaning (d − 56 to d − 14) period. Calves were gradually weaned over 14 days (d − 14 to d 0). Serological analysis for antibodies against key BRD pathogens (BRSV, BPI3V, BHV-1, BHV-4, BCoV, BVDV and H. somni) was undertaken at d − 14 and d 14. Linear regression models (for BVDV, BPI3V, BHV-1, BHV-4, BCoV and H. somni) and a single mixed effect random variable model (for BRSV) were used to identify risk factors for changes in antibody levels to these pathogens. RESULTS: BRSV was the only pathogen which demonstrated clustering by pen. Jersey calves experienced significantly lower changes in BVDV S/P than Holstein-Friesian calves. Animals with a high maximum respiratory score (≥8) recorded significant increases in H. somni S/P during the peri-weaning period when compared to those with respiratory scores of ≤3. Haptoglobin levels of between 1.32 and 1.60 mg/ml at d − 14 were significantly associated with decreases in BHV-1 S/N during the peri-weaning period. Higher BVDV S/P ratios at d − 14 were significantly correlated with increased changes in serological responses to BHV-4 over the peri-weaning period. CONCLUSIONS: Haptoglobin may have potential as a predictor of exposure to BHV-1. BRSV would appear to play a more significant role at the ‘group’ rather than ‘individual animal’ level. The significant associations between the pre-weaning levels of antibodies to certain BRD pathogens and changes in the levels of antibodies to the various pathogens during the peri-weaning period may reflect a cohort of possibly genetically linked ‘better responders’ among the study population.


title: An Insect Nidovirus Emerging from a Primary Tropical Rainforest

text: Tropical rainforests show the highest level of terrestrial biodiversity and may be an important contributor to microbial diversity. Exploitation of these ecosystems may foster the emergence of novel pathogens. We report the discovery of the first insect-associated nidovirus, tentatively named Cavally virus (CAVV). CAVV was found with a prevalence of 9.3% during a survey of mosquito-associated viruses along an anthropogenic disturbance gradient in Côte d’Ivoire. Analysis of habitat-specific virus diversity and ancestral state reconstruction demonstrated an origin of CAVV in a pristine rainforest with subsequent spread into agriculture and human settlements. Virus extension from the forest was associated with a decrease in virus diversity (P < 0.01) and an increase in virus prevalence (P < 0.00001). CAVV is an enveloped virus with large surface projections. The RNA genome comprises 20,108 nucleotides with seven major open reading frames (ORFs). ORF1a and -1b encode two large proteins that share essential features with phylogenetically higher representatives of the order Nidovirales, including the families Coronavirinae and Torovirinae, but also with families in a basal phylogenetic relationship, including the families Roniviridae and Arteriviridae. Genetic markers uniquely conserved in nidoviruses, such as an endoribonuclease- and helicase-associated zinc-binding domain, are conserved in CAVV. ORF2a and -2b are predicted to code for structural proteins S and N, respectively, while ORF3a and -3b encode proteins with membrane-spanning regions. CAVV produces three subgenomic mRNAs with 5′ leader sequences (of different lengths) derived from the 5′ end of the genome. This novel cluster of mosquito-associated nidoviruses is likely to represent a novel family within the order Nidovirales.


title: Identification of NCAM that interacts with the PHE-CoV spike protein

text: BACKGROUND: The spike proteins of coronaviruses associate with cellular molecules to mediate infection of their target cells. The characterization of cellular proteins required for virus infection is essential for understanding viral life cycles and may provide cellular targets for antiviral therapies. RESULTS: We identified Neural Cell Adhesion Molecule (NCAM) as a novel interacting partner of the PHE-CoV S protein. A T7 phage display cDNA library from N2a cells was constructed, and the library was screened with the soluble PHE-CoV S glycoproteins. We used a coimmunoprecipitation assay to show that only the NCAM was a binding partner of spike protein. We found that a soluble form of anti-NCAM antibody blocked association of the PHE-CoV with N2a cells. Furthermore, double-stranded siRNA targeted against NCAM inhibited PHE-CoV infection. CONCLUSIONS: A novel interaction was identified between NCAM and spike protein and this association is critical during PHE-CoV infection.


Astroviruses in bats, Madagascar


title: Design of Angiotensin‐converting Enzyme 2 (ACE2) Inhibitors by Virtual Lead Optimization and Screening

text: A group of presumed drug‐like molecules that possess high in silico affinity for angiotensin‐converting enzyme 2 were computationally designed. This enzyme is a promising new target in both cardiorenal disease and some coronavirus infections. A set of substrate analogous molecules were optimized by means of the LeapFrog module of the SYBYL package. Later, Molinspiration and Molsoft were used for screening out the compounds with low oral bioavailability. Similarly, OSIRIS was used for screening out the compounds having serious side effects. At the end of several stages of screening, seven candidates to anti‐viral drugs fulfiling all the evaluated criteria were obtained. They are amenable for future studies in vitro and in vivo. These designed ligands were finally evaluated by Quantitative Structure Activity Relationship studies. 21 molecules were used to carry out the qsar models. Fom these four molecules were taken as external sets yielding models with q (2) = 0.652 and r (2) = 0.962 values.