title: Herd-level risk factors associated with cow mortality in Swedish dairy herds

text: Abstract An increase in on-farm mortality (euthanasia and death) in dairy herds has been reported in several countries in the last decade. This does not only imply possible problems with animal welfare, but it also causes economic losses to the farmer. The objective of this study was to evaluate time trends in on-farm dairy cow mortality in Sweden and identify potential herd-level risk factors. Data were retrieved on all Swedish dairy herds enrolled in the milk recording scheme between 2002 and 2010. Herds with a herd size of <20 cows or a mortality rate (MR) of >40 dead or euthanized cows per 100 cow-years were excluded. Two different models were used: 1 multiple-year analysis, which included 6,898 herds during the period 2002 to 2010 and 1 single-year analysis including 4,252 herds for the year 2010, where other variables that were not present during the entire multiple year study were analyzed. The outcome variable was the number of euthanized and dead cows per year and season. A negative binomial regression model, adjusted for clustering within herd, was applied to both models. Fixed effects in the multiple-year analysis were breed, calving interval, herd size, milk yield, region, season, pasture period, and year. The fixed effects in the single-year analysis were breed, calving interval, conventional versus organic farming, herd size, housing system, milk yield, region, and season. The results demonstrated that MR gradually increased from 5.1 to 6.6 events per 100 cow-years during the study period. Swedish MR are consequently on par with, or even greater than, MR among dairy herds in other comparable countries. Higher mortality was associated with larger herd size, longer calving intervals, and herds that had Swedish Holstein as the predominant breed. Lower mortality was observed in herds with a higher herd average milk yield, during the fall and winter, and in organically managed herds. There were regional differences in mortality. An interaction between herd size and season was found in both models. Also, an interaction between housing system and milk yield was found in the single-year analysis. This first assessment of on-farm mortality in Swedish dairy herds confirmed that the MR has increased over the last few years. The study also identified some herd-level risk factors.


title: Evaluation of antibody responses against SARS coronaviral nucleocapsid or spike proteins by immunoblotting or ELISA

text: Severe acute respiratory syndrome (SARS)‐CoV is a newly emerging virus that causes SARS with high mortality rate in infected people. To study the humoral responses against SARS‐CoV, we evaluated nucleocapsid (N) and spike (S) proteins‐specific antibodies in patients' sera by Western blotting and enzyme‐linked immunosorbent assay (ELISA). Recombinant N and S proteins of SARS‐CoV were purified from transformed E. coli. Serum specimens from 40 SARS‐CoV‐infected patients in the convalescent phase were analyzed by Western blotting using the purified antigens. Serial serum specimens from 12 RT‐PCR‐confirmed SARS patients were assayed by ELISA using the recombinant N protein as coated antigen. By Western blotting, 97.5% of the SARS patients were positive for N protein‐specific antibodies whereas only 47.5% of the samples were positive for S protein‐specific antibodies. Using N protein‐based ELISA, 10 out of the 12 patients were positive for N protein‐specific antibodies and 6 of them showed seroconversion at mean of 16 days after onset of fever. Immunoblotting was useful for detecting the humoral immune response after SARS‐CoV infection. Antibodies against SARS‐CoV N protein appear at the early stage of infection, therefore, N protein‐based ELISA could serve as a simple, sensitive, and specific test for diagnosing SARS‐CoV infection. J. Med. Virol. 73:338–346, 2004. © 2004 Wiley‐Liss, Inc.


title: Chapter 9 Infections caused by rubella, reoviridae, retro, Norwalk and ronaviruses

text: Publisher Summary This chapter focuses on infections caused by rubella, reoviridae, retro, Norwalk and coronaviruses. High incidence of acute gastroenteritis caused by rotaviruses calls for prophylactic and therapeutic measures. Although no vaccine is presently available, it seems likely that vaccines will be developed in the next few years. There are also several rotavirus enzymes useful as targets for antiviral drugs. However, no antiviral drugs have shown therapeutic effects against rotavirus infections. The newly discovered human retrovirus (HTLV) has not yet been investigated in such detail as to predict the usefulness of vaccine or antiviral drugs. Several compounds are known to inhibit other retrovirus enzymes but the implication of this for chemotherapy of HTLV infection is unknown at present. The possibility and need for vaccination or chemotherapy against Norwalk virus and related agents is unclear. Very little work has been carried out to date with human coronaviruses, either from the point of view of vaccine development or specific antivirals. Both approaches may be usefully investigated in the future. Genetic cloning may be particularly useful for development of inactivated vaccines because the virus itself would be difficult to replicate and purify in large quantities for conventional vaccines.


title: Teicoplanin inhibits Ebola pseudovirus infection in cell culture

text: Abstract There is currently no approved antiviral therapy for treatment of Ebola virus disease. To discover readily available approved drugs that can be rapidly repurposed for treatment of Ebola virus infections, we screened 1280 FDA-approved drugs and identified glycopeptide antibiotic teicoplanin inhibiting Ebola pseudovirus infection by blocking virus entry in the low micromolar range. Teicoplanin could be evaluated further and incorporated into ongoing clinical studies.


title: Updates on Wuhan 2019 novel coronavirus epidemic

text: What emerged in December 2019 as a cluster of respiratory ailments with inexplicable etiological findings in Wuhan has now claimed roughly 259 lives, sickened nearly 12 thousand more, and spread to at least 26 more nations including Hong Kong, Taiwan and Macao. This article is protected by copyright. All rights reserved.


title: Running a Radiation Oncology Department at the Time of Coronavirus: An Italian Experience

text: Abstract Starting from Wuhan, China, SARS-CoV-2 has been a catastrophic epidemic involving many countries worldwide. After China, Italy has been heavily affected, and severe measures to limit the spread of the virus have been taken in the last weeks. Radiation oncology departments must guarantee optimal cancer treatments even in such a challenging scenario of an ongoing aggressive epidemic. Adopted preventive measures and recommendations are highlighted for patients, professionals, and clinical operations to minimize the risk of infection while safely treating patients with cancer.


title: Facing SARS: psychological impacts on SARS team nurses and psychiatric services in a Taiwan general hospital

text: Abstract Objective The outbreak of severe acute respiratory syndrome (SARS) in 2003 resulted in 346 probable SARS cases and 37 deaths in Taiwan. This descriptive study, which was conducted from May to June 2003, intended to identify staff stress and coping strategies among a SARS team of nursing staff during the outbreak. Method Twenty-six female nurses of the SARS team completed a questionnaire about their experiences serving in the SARS team. Results SARS had both positive and negative psychological impacts on the nurses. While worrying about infecting their families and colleagues, nurses were able to cope with the situation through various means. Additional findings include the need for more psychiatric staff to provide flexible and continuous service, the importance of meetings to improve teamwork and reduce conflict between doctors and nurses and the useful discovery that video cell phones provided needed reassurance from afar to the worried families of the nurses. Conclusion This study reinforces the importance and benefits of psychiatric services for SARS team members in reducing their secondary traumatization. It is hoped that the results will enhance our knowledge on the needs of frontline health care workers and support the planning of better psychiatric services in future epidemics.


title: Preparing to prevent severe acute respiratory syndrome and other respiratory infections

text: Summary Globalisation and its effect on human development has rendered an environment that is conducive for the rapid international spread of severe acute respiratory syndrome (SARS), and other new infectious diseases yet to emerge. After the unprecedented multi-country outbreak of avian influenza with human cases in the winter of 2003–2004, an influenza pandemic is a current threat. A critical review of problems and solutions encountered during the 2003–2004 SARS epidemics will serve as the basis for considering national preparedness steps that can be taken to facilitate the early detection of avian influenza, and a rapid response to an influenza pandemic should it occur.


title: Identification of novel reassortant mammalian orthoreoviruses from bats in Slovenia

text: BACKGROUND: Recently, mammalian orthoreoviruses (MRVs) were detected for the first time in European bats, and the closely related strain SI-MRV01 was isolated from a child with severe diarrhoea in Slovenia. Genetically similar strains have also been reported from other mammals, which reveals their wide host distribution. The aim of this study was to retrospectively investigate the occurrence and genetic diversity of MRVs in bats in Slovenia, from samples obtained throughout the country in 2008 to 2010, and in 2012 and to investigate the occurrence of the novel SI-MRV01 MRV variant in Slovenian bats. RESULTS: The detection of MRVs in bat guano was based on broad-range RT-PCR and specific bat MRV real-time RT-PCR. Subsequently, MRV isolates were obtained from cell culture propagation, with detailed molecular characterisation through whole-genome sequencing. Overall, bat MRVs were detected in 1.9% to 3.8% of bats in 2008, 2009 and 2012. However, in 2010 the prevalence was 33.0%, which defined an outbreak of the single SI-MRV01 strain. Here, we report on the identification of five MRV isolates of different serotypes that are designated as SI-MRV02, SI-MRV03, SI-MRV04, SI-MRV05 and SI-MRV06. There is high genetic variability between these characterised isolates, with evident genome reassortment seen across their genome segments. CONCLUSIONS: In conclusion, we have confirmed the presence of the SI-MRV01 strain in a Slovenian bat population. Moreover, according to genetic characterisation of S1 genome segment, all three MRV serotypes were present in the bat population. In this study, five independent MRV isolates were obtained and detailed whole genome analysis revealed high diversity between them. This study generates new information about the epidemiology and molecular characteristics of emerging bat MRV variants, and provides important molecular data for further studies of their pathogenesis and evolution. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-018-1585-y) contains supplementary material, which is available to authorized users.


title: A complexity-based measure and its application to phylogenetic analysis

text: In this article, we propose two well-defined distance metrics of biological sequences based on a universal complexity profile. To illustrate our metrics, phylogenetic trees of 18 Eutherian mammals from comparison of their mtDNA sequences and 24 coronaviruses using the whole genomes are constructed. The resulting monophyletic clusters agree well with the established taxonomic groups.


title: The hidden treasure in your data: phasing with unexpected weak anomalous scatterers from routine data sets

text: Single-wavelength anomalous dispersion (SAD) utilizing anomalous signal from native S atoms, or other atoms with Z ≤ 20, generally requires highly redundant data collected using relatively long-wavelength X-rays. Here, the results from two proteins are presented where the anomalous signal from serendipitously acquired surface-bound Ca atoms with an anomalous data multiplicity of around 10 was utilized to drive de novo structure determination. In both cases, the Ca atoms were acquired from the crystallization solution, and the data-collection strategy was not optimized to exploit the anomalous signal from these scatterers. The X-ray data were collected at 0.98 Å wavelength in one case and at 1.74 Å in the other (the wavelength was optimized for sulfur, but the anomalous signal from calcium was exploited for structure solution). Similarly, using a test case, it is shown that data collected at ∼1.0 Å wavelength, where the f′′ value for sulfur is 0.28 e, are sufficient for structure determination using intrinsic S atoms from a strongly diffracting crystal. Interestingly, it was also observed that SHELXD was capable of generating a substructure solution from high-exposure data with a completeness of 70% for low-resolution reflections extending to 3.5 Å resolution with relatively low anomalous multiplicity. Considering the fact that many crystallization conditions contain anomalous scatterers such as Cl, Ca, Mn etc., checking for the presence of fortuitous anomalous signal in data from well diffracting crystals could prove useful in either determining the structure de novo or in accurately assigning surface-bound atoms.


title: Controlling timing and location in vaccines

text: Vaccines are one of the most powerful technologies supporting public health. The adaptive immune response induced by immunization arises following appropriate activation and differentiation of T and B cells in lymph nodes. Among many parameters impacting the resulting immune response, the presence of antigen and inflammatory cues for an appropriate temporal duration within the lymph nodes, and further within appropriate subcompartments of the lymph nodes– the right timing and location– play a critical role in shaping cellular and humoral immunity. Here we review recent advances in our understanding of how vaccine kinetics and biodistribution impact adaptive immunity, and the underlying immunological mechanisms that govern these responses. We discuss emerging approaches to engineer these properties for future vaccines, with a focus on subunit vaccines.


title: Signaling pathways and therapeutic perspectives related to environmental factors associated with multiple sclerosis

text: Multiple sclerosis (MS) is an immune‐mediated demyelinating disorder of unknown etiology. Both genetic‐susceptibility and environment exposures, including vitamin D deficiency, Epstein‐Barr viral and Herpesvirus (HHV‐6) infections are strongly implicated in the activation of T cells and MS‐pathogenesis. Despite precise knowledge of how these factors could be operating alone or in combination to facilitate and aggravate the disease progression, it is clear that prolonged induction of inflammatory molecules and recruitment of other immune cells by the activated T cells results in demyelination and axonal damage. It is imperative to understand the risk factors associated with MS progression and how these factors contribute to disease pathology. Understanding of the underlying mechanisms of what factors triggers activation of T cells to attack myelin antigen are important to strategize therapeutics and therapies against MS. Current review provides a detailed literature to understand the role of both pathogenic and non‐pathogenic factors on the impact of MS.


title: Contamination, Disinfection, and Cross-Colonization: Are Hospital Surfaces Reservoirs for Nosocomial Infection?

text: Despite documentation that the inanimate hospital environment (e.g., surfaces and medical equipment) becomes contaminated with nosocomial pathogens, the data that suggest that contaminated fomites lead to nosocomial infections do so indirectly. Pathogens for which there is more-compelling evidence of survival in environmental reservoirs include Clostridium difficile, vancomycin-resistant enterococci, and methicillin-resistant Staphylococcus aureus, and pathogens for which there is evidence of probable survival in environmental reservoirs include norovirus, influenza virus, severe acute respiratory syndrome—associated coronavirus, and Candida species. Strategies to reduce the rates of nosocomial infection with these pathogens should conform to established guidelines, with an emphasis on thorough environmental cleaning and use of Environmental Protection Agency—approved detergent-disinfectants.


Characteristics of Traveler with Middle East Respiratory Syndrome, China, 2015


SARS-CoV Sampling from 3 Portals


title: Pathogenicity-associated protein domains: The fiercely-conserved evolutionary signatures

text: Abstract Proteins have highly conserved domains that determine their functionality. Out of the thousands of domains discovered so far across all living forms, some of the predominant clinically-relevant domains include IENR1, HNHc, HELICc, Pro-kuma_activ, Tryp_SPc, Lactamase_B, PbH1, ChtBD3, CBM49, acidPPc, G3P_acyltransf, RPOL8c, KbaA, HAMP, HisKA, Hr1, Dak2, APC2, Citrate_ly_lig, DALR, VKc, YARHG, WR1, PWI, ZnF_BED, TUDOR, MHC_II_beta, Integrin_B_tail, Excalibur, DISIN, Cadherin, ACTIN, PROF, Robl_LC7, MIT, Kelch, GAS2, B41, Cyclin_C, Connexin_CCC, OmpH, Bac_rhodopsin, AAA, Knot1, NH, Galanin, IB, Elicitin, ACTH, Cache_2, CHASE, AgrB, PRP, IGR, and Antimicrobial21. These domains are distributed in nucleases/helicases, proteases, esterases, lipases, glycosylase, GTPases, phosphatases, methyltransferases, acyltransferase, acetyltransferase, polymerase, kinase, ligase, synthetase, oxidoreductase, protease inhibitors, nucleic acid binding proteins, adhesion and immunity-related proteins, cytoskeletal component-manipulating proteins, lipid biosynthesis and metabolism proteins, membrane-associated proteins, hormone-like and signaling proteins, etc. These domains are ubiquitous stretches or folds of the proteins in pathogens and allergens. Pathogenesis alleviation efforts can benefit enormously if the characteristics of these domains are known. Hence, this review catalogs and discusses the role of such pivotal domains, suggesting hypotheses for better understanding of pathogenesis at molecular level.


title: Emergence of Pathogenic Coronaviruses in Cats by Homologous Recombination between Feline and Canine Coronaviruses

text: Type II feline coronavirus (FCoV) emerged via double recombination between type I FCoV and type II canine coronavirus (CCoV). In this study, two type I FCoVs, three type II FCoVs and ten type II CCoVs were genetically compared. The results showed that three Japanese type II FCoVs, M91-267, KUK-H/L and Tokyo/cat/130627, also emerged by homologous recombination between type I FCoV and type II CCoV and their parent viruses were genetically different from one another. In addition, the 3′-terminal recombination sites of M91-267, KUK-H/L and Tokyo/cat/130627 were different from one another within the genes encoding membrane and spike proteins, and the 5′-terminal recombination sites were also located at different regions of ORF1. These results indicate that at least three Japanese type II FCoVs emerged independently. Sera from a cat experimentally infected with type I FCoV was unable to neutralize type II CCoV infection, indicating that cats persistently infected with type I FCoV may be superinfected with type II CCoV. Our previous study reported that few Japanese cats have antibody against type II FCoV. All of these observations suggest that type II FCoV emerged inside the cat body and is unable to readily spread among cats, indicating that these recombination events for emergence of pathogenic coronaviruses occur frequently.


title: VIRULENCE FACTORS IN PORCINE CORONAVIRUSES AND VACCINE DESIGN

text: Porcine enteric coronaviruses (CoVs) cause severe disease in the porcine herds worldwide, leading to important economic losses. Despite the knowledge of these viruses since the 1970’s, vaccination strategies have not been implemented, leading to continuous re-emergence of novel virulent strains. Live attenuated vaccines historically have been the most efficient. We consider that the new trend is the development of recombinant vaccines by using reverse genetics systems to engineer attenuated viruses, which could be used as effective and safe modified live vaccine candidates. To this end, host cell signaling pathways influencing porcine CoV virulence should be identified. Similarly, the identity of viral proteins involved in the modulation of host cell pathways influencing CoV pathogenesis should be analyzed. With this information, and using reverse genetics systems, it is possible to design viruses with modifications in the viral proteins acting as virulence factors, which may lead to attenuated viruses and, therefore, vaccine candidates. In addition, novel antiviral drugs may be developed once the host cell pathways and the molecular mechanism affecting porcine CoV replication and virulence are known. This review is focused in the host cell responses to enteric porcine CoV infection and the viral proteins involved in pathogenesis.


title: Equine arteritis virus

text: Abstract Equine arteritis virus (EAV) is the causative agent of equine viral arteritis (EVA), a respiratory and reproductive disease of equids. There has been significant recent progress in understanding the molecular biology of EAV and the pathogenesis of its infection in horses. In particular, the use of contemporary genomic techniques, along with the development and reverse genetic manipulation of infectious cDNA clones of several strains of EAV, has generated significant novel information regarding the basic molecular biology of the virus. Therefore, the objective of this review is to summarize current understanding of EAV virion architecture, replication, evolution, molecular epidemiology and genetic variation, pathogenesis including the influence of host genetics on disease susceptibility, host immune response, and potential vaccination and treatment strategies.


title: Health Care in China

text: China has recently emerged as an important global partner. However, like other developing nations, China has experienced dramatic demographic and epidemiologic changes in the past few decades. Population discontent with the health care system has led to major reforms. China’s distinctive health care system, including its unique history, vast infrastructure, the speed of health reform, and economic capacity to make important advances in health care, nonetheless, has incomplete insurance coverage for urban and rural dwellers, uneven access, mixed quality of health care, increasing costs, and risk of catastrophic health expenditures.


title: C1‐INH and the contact system in COVID‐19

text: COVID‐19 is frequently associated with severe systemic consequences, including vasculitis, a hyperinflammatory state and hypercoagulation. The mechanisms leading to these life‐threatening abnormalities are multifactorial. Based on the analysis of publicly available interactomes, we propose that SARS‐CoV‐2 infection directly causes a deficiency in C1 esterase inhibitor (C1‐INH), a pathogen‐specific mechanism that may help explain significant systemic abnormalities in COVID‐19 patients.


title: Lessons learned in preparing for and responding to the early stages of the COVID-19 pandemic: one simulation’s program experience adapting to the new normal

text: Use of simulation to ensure an organization is ready for significant events, like COVID-19 pandemic, has shifted from a “backburner” training tool to a “first choice” strategy for ensuring individual, team, and system readiness. In this report, we summarize our simulation program’s response during the COVID-19 pandemic, including the associated challenges and lessons learned. We also reflect on anticipated changes within our program as we adapt to a “new normal” following this pandemic. We intend for this report to function as a guide for other simulation programs to consult as this COVID-19 crisis continues to unfold, and during future challenges within global healthcare systems. We argue that this pandemic has cemented simulation programs as fundamental for any healthcare organization interested in ensuring its workforce can adapt in times of crisis. With the right team and set of partners, we believe that sustained investments in a simulation program will amplify into immeasurable impacts across a healthcare system.


title: 40 Group A Streptococcus

text: Abstract Group A Streptococcus (GAS) or Streptococcus pyogenes, affects an estimated 800 million people each year. Most of the resulting estimated 639,000 annual deaths are related to rheumatic heart disease (RHD) and its complications. Resource-limited areas account for the vast majority of cases, although outbreaks still occur in industrialized countries. GAS has several mechanisms to avoid phagocytosis, including prevention of opsonization and the use of surface proteins to block complement fixation. The mechanisms behind the immunologic phenomenon are not well understood. Clinical presentations range from benign, short-lived impetigo or pharyngitis through to lifelong RHD. In its most invasive form, GAS can cause a rapidly progressive, often lethal infection: streptococcal toxic shock syndrome. S. pyogenes remains universally sensitive to penicillin, which is the mainstay of treatment.


title: Evolution and Emergence of Pathogenic Viruses: Past, Present, and Future

text: Incidences of emerging/re-emerging deadly viral infections have significantly affected human health despite extraordinary progress in the area of biomedical knowledge. The best examples are the recurring outbreaks of dengue and chikungunya fever in tropical and sub-tropical regions, the recent epidemic of Zika in the Americas and the Caribbean, and the SARS, MERS, and influenza A outbreaks across the globe. The established natural reservoirs of human viruses are mainly farm animals, and, to a lesser extent, wild animals and arthropods. The intricate “host-pathogen-environment” relationship remains the key to understanding the emergence/re-emergence of pathogenic viruses. High population density, rampant constructions, poor sanitation, changing climate, and the introduction of anthropophilic vectors create selective pressure on host-pathogen reservoirs. Nevertheless, the knowledge and understanding of such zoonoses and pathogen diversity in their known non-human reservoirs are very limited. Prevention of arboviral infections using vector control methods has not been very successful. Currently, new approaches to protect against food-borne infections, such as consuming only properly cooked meats and animal products, are the most effective control measures. Though significant progress in controlling human immunodeficiency virus and hepatitis viruses has been achieved, the unpredictable nature of evolving viruses and the rare occasions of outbreaks severely hamper control and preventive modalities.


Coronavirus disease – 2019 assessment zone: A community hospital's rapid response to a novel infectious pandemic


title: Acute urticaria with pyrexia as the first manifestations of a COVID‐19 infection

text: The coronavirus disease 2019 (COVID‐19) affects principally the respiratory tract but recent studies described that COVID‐19 could present a broader clinical spectrum from the absence of any symptoms to heart (1), digestive (2) or Ear‐Nose‐Throat (including anosmia and ageusia) (3) manifestations. Here we report two cases of peculiar skin manifestation.


The puzzle of sharing bio-molecular targets between coronaviruses and mediators of the cardiovascular system in humans: looking for plausible hypotheses


Papel de la Hemodiálisis Extendida (HDx) en COVID-19: A propósito de un caso


title: Heteroaggregation of an enveloped bacteriophage with colloidal sediments and effect on virus viability

text: Abstract Four sediments in the colloidal size range: goethite, montmorillonite, illite, and kaolinite, were suspended with the bacteriophage φ6, a model enveloped virus, to determine relative rates of heteroaggregation and the effect of aggregation on virus viability. Turbidity was measured on combinations of virus and each sediment type at low concentration to determine aggregation rates. Aggregation of sediment with virus occurred regardless of mineral type, and larger fraction of virus is expected to aggregate with increasing sediment concentration leading to higher deposition rates. The negatively charged sediments, aggregated with φ6 (also negatively charged at neutral pH) at a faster rate than the positively charged sediments, yielding turbidity slopes of 4.94 × 10−3 s−1 and 7.50 × 10−4 s−1 for φ6-montmorillonite and φ6-illite aggregates, respectively, and 2.98 × 10−5 s−1 and 2.84 × 10−5 s−1, for φ6-goethite and φ6-kaolinite, respectively. This indicates that the interaction between sediments and virus is hydrophobic, rather than electrostatic. Large numbers of virions remained viable post-aggregation, despite the fragility of the viral envelope, indicating that small-sized aggregates, which may travel more readily through porous media, may pose an infection risk. The fraction of φ6 that remained viable varied with sediment type, with montmorillonite-φ6 aggregates experiencing the greatest reduction in infectivity at 35%. TEM analyses reveal that in all sediment-φ6 combinations, infectivity loss was likely due to disassembly of the viral envelope as a result of aggregation.


title: Proposal for International Standardization of the Use of Lung Ultrasound for Patients With COVID‐19: A Simple, Quantitative, Reproducible Method

text: Growing evidence is showing the usefulness of lung ultrasound in patients with the 2019 new coronavirus disease (COVID‐19). Severe acute respiratory syndrome coronavirus 2 has now spread in almost every country in the world. In this study, we share our experience and propose a standardized approach to optimize the use of lung ultrasound in patients with COVID‐19. We focus on equipment, procedure, classification, and data sharing.


title: The evidence of SARS-CoV-2 infection on ocular surface

text: Abstract This is a cross-sectional study of patients who received a COVID-19 diagnosis between December 30, 2019 and February 7, 2020 at Tongji Hospital. A total of 102 patients (48 Male [47%] and 54 Female [53%]) with clinical symptoms, Rt, and chest Computed Tomography (CT) abnormalities were identified with a clinical diagnosis of COVID-19. Patients had a mean [SD] gestational age of 57.63 [14.90] years. Of a total of 102 patients identified, 72 patients (36 men [50%] and 36 women [50%]; mean [SD] age, 58.68 [14.81] years) were confirmed to have COVID-19 by laboratory diagnosis with a SARS-CoV-2 RT-PCR assay. Only two patients (2.78%) with conjunctivitis were identified from 72 patients with a laboratory confirmed COVID-19. Of those two patients, SARS-CoV-2 RNA fragments were found in ocular discharges by SARS-CoV-2 RT-PCR in only one patient. Our findings suspect the incidence of SARS-CoV-2 infection through the ocular surface is extremely low, while the nosocomial infection of SARS-CoV-2 through the eyes after occupational exposure is a potential route. To lower the SARS-CoV-2 nosocomial infection, all health care professionals should wear protective goggles. The inefficient diagnostic method and the sampling time lag may contribute to the lower positive rate of conjunctival swab samples of SARS-CoV-2.


A “paper diaper” in N95 respirator


title: STEMI During the COVID-19 Pandemic - An Evaluation of Incidence

text: Abstract The COVID-19 pandemic has dramatically changed the practice medicine on a global scale during the year 2020. With fewer patients presenting to hospitals with the diagnosis of STEMI, healthcare workers are wondering what is causing this decline. This piece presents data from two medical centers and addresses several possible causes to explain this phenomenon. It was found that there was a statistically significant decrease from January to March 2020 in number of presenting STEMI diagnoses.


title: Agent-based scenarios comparison for assessing fuel-switching investment in long-term energy transitions of the India’s industry sector

text: This paper presents the formulation and application of a novel agent-based integrated assessment approach to model the attributes, objectives and decision-making process of investors in a long-term energy transition in India’s iron and steel sector. It takes empirical data from an on-site survey of 108 operating plants in Maharashtra to formulate objectives and decision-making metrics for the agent-based model and simulates possible future portfolio mixes. The studied decision drivers were capital costs, operating costs (including fuel consumption), a combination of capital and operating costs, and net present value. Where investors used a weighted combination of capital cost and operating costs, a natural gas uptake of ~12PJ was obtained and the highest cumulative emissions reduction was obtained, 2 Mt CO(2) in the period from 2020 to 2050. Conversely if net present value alone is used, cumulative emissions reduction in the same period was lower, 1.6 Mt CO(2), and the cumulative uptake of natural gas was equal to 15PJ. Results show how the differing upfront investment cost of the technology options could cause prevalence of high-carbon fuels, particularly heavy fuel oil, in the final mix. Results also represent the unique heterogeneity of fuel-switching industrial investors with distinct investment goals and limited foresight on costs. The perception of high capital expenditures for decarbonisation represents a significant barrier to the energy transition in industry and should be addressed via effective policy making (e.g. carbon policy/price).


title: Further in vitro characterization of mouse hepatitis virus papain-like proteinase 1: Cleavage sequence requirements within PP1a

text: Proteolytic processing of the mouse hepatitis virus strain A59 (MHV-A59) replicase gene product, pp1a, results in polypeptides p28, p65, p50, and p240 in infected cells. Based on previously identified p28 and p65 cleavage sites, a p50 cleavage site was proposed to occur between Ala-1262 and Ala-1263. Results of mutagenesis and in vitro cleavage assays show that PLP-1 was able to cleave in trans when the proposed p50 cleavage sequence replaced the p28 cleavage sequence. Mutagenesis was also used to investigate cleavage between Gly-904 and Val-905, a cleavage site predicted to produce a precursor of p65, p72, that was detected in cells infected with MHV strain JHM, but not with MHV-A59. No cleavage could be detected using substrate that carried both the p65 site and the predicted p72 cleavage sequence. Thus, it appeared that PLP-1 could recognize the proposed p50 sequence but not the predicted p72 site under the in vitro conditions used.


title: Single-Domain Antibodies and Their Formatting to Combat Viral Infections

text: Since their discovery in the 1990s, single-domain antibodies (VHHs), also known as Nanobodies(®), have changed the landscape of affinity reagents. The outstanding solubility, stability, and specificity of VHHs, as well as their small size, ease of production and formatting flexibility favor VHHs over conventional antibody formats for many applications. The exceptional ease by which it is possible to fuse VHHs with different molecular modules has been particularly explored in the context of viral infections. In this review, we focus on VHH formats that have been developed to combat viruses including influenza viruses, human immunodeficiency virus-1 (HIV-1), and human respiratory syncytial virus (RSV). Such formats may significantly increase the affinity, half-life, breadth of protection of an antiviral VHH and reduce the risk of viral escape. In addition, VHHs can be equipped with effector functions, for example to guide components of the immune system with high precision to sites of viral infection.


Care for critically Ill patients with COVID-19: don’t forget the eyes


title: Public perceptions, anxiety, and behaviour change in relation to the swine flu outbreak: cross sectional telephone survey

text: Objective To assess whether perceptions of the swine flu outbreak predicted changes in behaviour among members of the public in England, Scotland, and Wales. Design Cross sectional telephone survey using random digit dialling. Setting Interviews by telephone between 8 and 12 May. Participants 997 adults aged 18 or more who had heard of swine flu and spoke English. Main outcome measures Recommended change in behaviour (increases in handwashing and surface cleaning or plans made with a “flu friend”) and avoidance behaviours (engaged in one or more of six behaviours such as avoiding large crowds or public transport). Results 37.8% of participants (n=377) reported performing any recommended behaviour change “over the past four days . . . because of swine flu.” 4.9% (n=49) had carried out any avoidance behaviour. Controlling for personal details and anxiety, recommended changes were associated with perceptions that swine flu is severe, that the risk of catching it is high risk, that the outbreak will continue for a long time, that the authorities can be trusted, that good information has been provided, that people can control their risk of catching swine flu, and that specific behaviours are effective in reducing the risk. Being uncertain about the outbreak and believing that the outbreak had been exaggerated were associated with a lower likelihood of change. The strongest predictor of behaviour change was ethnicity, with participants from ethnic minority groups being more likely to make recommended changes (odds ratio 3.2, 95% confidence interval 2.0 to 5.3) and carry out avoidance behaviours (4.1, 2.0 to 8.4). Conclusions The results support efforts to inform the public about specific actions that can reduce the risks from swine flu and to communicate about the government’s plans and resources. Tackling the perception that the outbreak has been “over-hyped” may be difficult but worthwhile. Additional research is required into differing reactions to the outbreak among ethnic groups.


title: High prevalence of olfactory and taste disorder during SARS‐CoV‐2 infection in outpatients

text: Prevalent symptoms of SARS-CoV-2 in reports and metaanalyses refer to cough, fatigue, myalgia and respiratory distress. These represent clinically acknowledged relevant findings of valuable importance, particularly with the requirement for ventilation and hospital bed occupancy in ICUs. There is however a wide discordance with the actual picture of clinical presentation and symptoms in Italy. Here we comment on Sun and coll Metaanlysis with particular nuance to olfactory and taste disorders that very often herald SARS-CoV-2 in our country, particularly in outpatients, and are not reported so far in the medical literature from China. This article is protected by copyright. All rights reserved.


title: Basic public health services delivered in an urban community: a qualitative study

text: Summary Objectives To understand the advancements in and barriers to the implementation of measures to improve basic public health services in an urban Chinese community. Study design A qualitative study based on semi-structured interviews. Interviews were audio-taped, transcribed and analysed using thematic content analysis. Methods In-depth interviews were undertaken with the directors of the management centres for community health services in 15 of the 18 districts in Beijing from December 2008 to February 2009. Content analysis of the data was completed in May 2009. Results Fifteen types of free basic public health services had been delivered in Beijing. Some were supplied at a low level. An average of £2.38 per person per year was provided for inhabitants since 2008, but demand for funding far exceeded monies available. Teams consisting of general practitioners, community nurses and public health specialists delivered these services. The number of practitioners and their low levels of skill were insufficient to provide adequate services for community residents. Respondents gave recommendations of how to resolve the above problems. Conclusions In order to improve the delivery of basic public health services, it is necessary for Beijing Municipal Government to supply clear and detailed protocols, increase funding and increase the number of skilled practitioners in the community health services.


title: ISG15: It's Complicated

text: Abstract Interferon-stimulated gene product 15 (ISG15) is a key component of host responses to microbial infection. Despite having been known for four decades, grasping the functions and features of ISG15 has been a slow and elusive process. Substantial work over the past two decades has greatly enhanced this understanding, revealing the complex and variable nature of this protein. This has unveiled multiple mechanisms of action that are only now beginning to be understood. In addition, it has uncovered diversity not only between how ISG15 affects different pathogens but also between the function and structure of ISG15 itself between different host species. Here we review the complexity of ISG15 within the context of viral infection, focusing primarily on its antiviral function and the mechanisms viruses employ to thwart its effects. We highlight what is known regarding the impact of ISG15 sequence and structural diversity on these interactions and discuss the aspects presenting the next frontier toward elucidating a more complete picture of ISG15 function.


title: Porcine endemic diarrhea virus infection regulates long noncoding RNA expression

text: Abstract Long noncoding RNAs (lncRNAs) have been implicated in various life processes. However, the lncRNA expression and potential functions in porcine endemic diarrhea virus (PEDV) infection and host defense are still poorly understood. In this study, we investigated the lncRNA expression profiles during PEDV infection in intestinal porcine epithelial cell-jejunum 2 (IPEC-J2) cell lines by next-generation sequencing and identified 6188 novel lncRNAs. The functional annotation analysis revealed that these lncRNAs might be associated with many immunity-related genes. We next selected candidate lncRNAs related to immune response pathways and further identified their differential expression in PEDV-infected IPEC-J2 cells and newborn piglets. Our results demonstrated that PEDV infection regulated lncRNA expression patterns in both the IPEC-J2 cell line and piglet ileum. These findings provide the first large-scale survey of lncRNAs associated with PEDV infection, specifically the lncRNAs responsible for the activation of the immune system within the ileum.


COVID-19 crisis: time to reflect on how we live and interact with nature


title: Baculovirus expression of HCoV-OC43 nucleocapsid protein and development of a Western blot assay for detection of human antibodies against HCoV-OC43

text: Abstract The nucleocapsid (N) gene of human coronavirus strain OC43 (HCoV-OC43) was amplified by reverse transcriptase-polymerase chain reaction, and cloned in pENTR™/D-TOPO® plasmid. This plasmid containing the N gene was recombined with in a BaculoDirect™ baculovirus DNA designed in order to express N protein in fusion with a C-terminal polyhistidine tag containing V5 epitope. Sf21 cells were transfected with recombinant baculovirus DNA. Recombinant N protein was extracted from infected cells, analysed by SDS-PAGE and Western blot, and purified by Ni2+ affinity procedure. Sera from 100 healthcare workers and five 2–3-year-old children were tested in a Western blot assay using the purified recombinant N protein. All of the sera from adults and two of the sera from children have a positive result.


title: Current Knowledge on Porcine circovirus 3 (PCV-3): A Novel Virus With a Yet Unknown Impact on the Swine Industry

text: Porcine circovirus 3 (PCV-3) is a recently described virus belonging to the family Circoviridae. It represents the third member of genus Circovirus able to infect swine, together with PCV-1, considered non-pathogenic, and PCV-2, one of the most economically relevant viruses for the swine worldwide industry. PCV-3 was originally found by metagenomics analyses in 2015 in tissues of pigs suffering from porcine dermatitis and nephropathy syndrome, reproductive failure, myocarditis and multisystemic inflammation. The lack of other common pathogens as potential infectious agents of these conditions prompted the suspicion that PCV-3 might etiologically be involved in disease occurrence. Subsequently, viral genome was detected in apparently healthy pigs, and retrospective studies indicated that PCV-3 was already present in pigs by early 1990s. In fact, current evidence suggests that PCV-3 is a rather widespread virus worldwide. Recently, the virus DNA has also been found in wild boar, expanding the scope of infection susceptibility among the Suidae family; also, the potential reservoir role of this species for the domestic pig has been proposed. Phylogenetic studies with available PCV-3 partial and complete sequences from around the world have revealed high nucleotide identity (>96%), although two main groups and several subclusters have been described as well. Moreover, it has been proposed the existence of a most common ancestor dated around 50 years ago. Taking into account the economic importance and the well-known effects of PCV-2 on the swine industry, a new member of the same family like PCV-3 should not be neglected. Studies on epidemiology, pathogenesis, immunity and diagnosis are guaranteed in the next few years. Therefore, the present review will update the current knowledge and future trends of research on PCV-3.


title: Reverse genetics approaches: a novel strategy for African horse sickness virus vaccine design

text: African horse sickness (AHS) is a devastating disease caused by African horse sickness virus (AHSV) and transmitted by arthropods between its equine hosts. AHSV is endemic in sub-Saharan Africa, where polyvalent live attenuated vaccine is in use even though it is associated with safety risks. This review article summarizes and compares new strategies to generate safe and effective AHSV vaccines based on protein, virus like particles, viral vectors and reverse genetics technology. Manipulating the AHSV genome to generate synthetic viruses by means of reverse genetic systems has led to the generation of potential safe vaccine candidates that are under investigation.


title: Evaluation of an immunochemotherapeutic protocol constituted of N-methyl meglumine antimoniate (Glucantime®) and the recombinant Leish-110f® +MPL-SE® vaccine to treat canine visceral leishmaniasis

text: Summary The evaluation of the efficacy of an immunochemotherapy protocol to treat symptomatic dogs naturally infected with Leishmania chagasi was studied. This clinical trial had the purpose to test the combination of N-methyl meglumine antimoniate (Glucantime®) and the second generation recombinant vaccine Leish-110f® plus the adjuvant MPL-SE® to treat the canine leishmaniasis (CanL). Thirty symptomatic naturally infected mongrel dogs were divided into five groups. Animals received standard treatment with Glucantime® or treatment with Glucantime®/Leish-110f® +MPL-SE® as immunochemotherapy protocol. Additional groups received Leish-110f® +MPL-SE® only, MPL-SE® only, or placebo. Evaluation of haematological, biochemical (renal and hepatic function) and plasmatic proteins, immunological (humoral and cellular immune response) and the parasitological test revealed improvement of the clinical parameters and parasitological cure in dogs in both chemotherapy alone and immunochemotherapy cohorts. However, the immunotherapy and immunochemotherapy cohorts had reduced number of deaths, higher survival probability, and specific cellular reactivity to leishmanial antigens, in comparison with chemotherapy cohort only and control groups (adjuvant alone and placebo). These results support the notion of using well-characterized recombinant vaccine as an adjunct to improve the current chemotherapy of CanL.


title: Gene Expression Profiling: From Microarrays to Medicine

text: With the mapping of the human genome comes the ability to identify genes of interest in specific diseases and the pathways involved therein. Laboratory technology has evolved in parallel, providing us with the ability to assay thousands of these genes at once, a technique known as microarray analysis. The main #x003Fion that this type of technology raises is how we can apply this powerful technology to clinical medicine. Recently, advances in data analysis, as well as standardization of the technology, have allowed us to examine this #x003Fion, and indeed a few clinical trials currently being performed include microarrays as part of their protocol. In this review we outline the microarray technique and describe these types of studies in further detail.


title: Therapeutic Antibodies: Current State and Future Trends – Is a Paradigm Change Coming Soon?

text: Antibody-based therapeutics currently enjoy unprecedented success, growth in research and revenues, and recognition of their potential. It appears that the promise of the “magic bullet” has largely been realized. There are currently 22 monoclonal antibodies (mAbs) approved by the United States Food and Drug Administration (FDA) for clinical use and hundreds are in clinical trials for treatment of various diseases including cancers, immune disorders, and infections. The revenues from the top five therapeutic antibodies (Rituxan, Remicade, Herceptin, Humira, and Avastin) nearly doubled from $6.4 billion in 2004 to $11.7 billion in 2006. During the last several years major pharmaceutical companies raced to acquire antibody companies, with a recent example of MedImmune being purchased for $15.6 billion by AstraZeneca. These therapeutic and business successes reflect the major advances in antibody engineering which have resulted in the generation of safe, specific, high-affinity, and non-immunogenic antibodies during the last three decades. Currently, second and third generations of antibodies are under development, mostly to improve already existing antibody specificities. However, although the refinement of already known methodologies is certainly of great importance for potential clinical use, there are no conceptually new developments in the last decade comparable, for example, to the development of antibody libraries, phage display, domain antibodies (dAbs), and antibody humanization to name a few. A fundamental question is then whether there will be another change in the paradigm of research as happened 1–2 decades ago or the current trend of gradual improvement of already developed methodologies and therapeutic antibodies will continue. Although any prediction could prove incorrect, it appears that conceptually new methodologies are needed to overcome the fundamental problems of drug (antibody) resistance due to genetic or/and epigenetic alterations in cancer and chronic infections, as well as problems related to access to targets and complexity of biological systems. If new methodologies are not developed, it is likely that gradual saturation will occur in the pipeline of conceptually new antibody therapeutics. In this scenario we will witness an increase in combination of targets and antibodies, and further attempts to personalize targeted treatments by using appropriate biomarkers as well as to develop novel scaffolds with properties that are superior to those of the antibodies now in clinical use.


title: Predictors of progression from moderate to severe COVID-19: a retrospective cohort

text: OBJECTIVE: Most coronavirus disease 2019 (COVID-19) cases were identified as moderate, which is defined as having a fever or dry cough and lung imaging with ground-glass opacities. The risk factors and predictors of prognosis in such cohorts remain uncertain. METHODS: All adult patients with COVID-19 of moderate severity diagnosed using qRT-PCR and hospitalized at the Central Hospital of Wuhan, China, from Jan 1 to Mar 20, 2020 were enrolled in this retrospective study. The main outcomes were progression from moderate to severe or critical condition or death. RESULTS: Among the 456 enrolled patients with moderate COVID-19, 251/456 (55.0%) had poor prognosis. Multivariate logistic regression analysis identified higher NLR on admission (OR =1.032, 95%CI 1.042-1.230, P = 0.004) and higher CRP on admission (OR =3.017, 95%CI 1.941-4.690, P < 0.001) were associated with increased odds ratios of poor prognosis. The area under the receiver operating characteristic (ROC) curve (AUC) for NLR and CRP in predicting progression to critical condition was 0.77 (95% CI 0.694-0.846, P < 0.001) and 0.84 (95% CI 0.780-0.905, P < 0.001), with a cut-off value of 2.79 and 25.95 mg/l, respectively. The AUC of NLR and CRP in predicting death was 0.81 (95% CI, 0.732-0.878, P < 0.001) and 0.89 (95% CI 0.825-0.946, P < 0.001), with a cut-off value of 3.19 and 33.4 mg/l, respectively. CONCLUSIONS: Higher levels of NLR and CRP at admission were associated with poor prognosis of moderate COVID-19 patients. NLR and CRP were good predictors of progression to critical condition and death.


title: Sequence analysis of SARS-CoV-2 genome reveals features important for vaccine design

text: As the SARS-CoV-2 pandemic is rapidly progressing, the need for the development of an effective vaccine is critical. A promising approach for vaccine development is to generate, through codon pair deoptimization, an attenuated virus. This approach carries the advantage that it only requires limited knowledge specific to the virus in question, other than its genome sequence. Therefore, it is well suited for emerging viruses for which we may not have extensive data. We performed comprehensive in silico analyses of several features of SARS-CoV-2 genomic sequence (e.g., codon usage, codon pair usage, dinucleotide/junction dinucleotide usage, RNA structure around the frameshift region) in comparison with other members of the coronaviridae family of viruses, the overall human genome, and the transcriptome of specific human tissues such as lung, which are primarily targeted by the virus. Our analysis identified the spike (S) and nucleocapsid (N) proteins as promising targets for deoptimization and suggests a roadmap for SARS-CoV-2 vaccine development, which can be generalizable to other viruses.


title: FSDB: A frameshift signal database

text: Abstract Programmed frameshifting is a recoding event in which a ribosome shifts reading frame by one or more nucleotides at a specific mRNA signal between overlapping genes. Programmed frameshifting is involved in the expression of many genes in a wide range of organisms, especially in viruses and bacteria. The mechanism of programmed frameshifting is not fully understood despite many studies, and there are few databases available for detailed information on programmed frameshifting. We have developed a database called FSDB (Frameshift Signal Database), which is a comprehensive compilation of experimentally known or computationally predicted data about programmed ribosomal frameshifting. FSDB provides a graphical view of frameshift signals and the genes using programmed frameshifting for their expression. It also allows the user himself/herself to find programmed frameshift sites in genomic sequences using a program called FSFinder (http://wilab.inha.ac.kr/fsfinder2). We believe FSDB will be a valuable resource for scientists studying programmed ribosomal frameshifting. FSDB is freely accessible at http://wilab.inha.ac.kr/fsdb/.


title: Chapter 15 Analysis of alkaloids (indole alkaloids, isoquinoline alkaloids, tropane alkaloids)

text: Abstract Alkaloids are a large cluster of molecules found in Mother Nature all over the world. They are all secondary compounds and collection of miscellaneous elements and biomolecules, derived from amino acids or from transamination. This diverse chemical group is categorized, based on the amino acids that deliver their nitrogen atom and part of their skeleton. Alkaloids from a similar origin or having the same basic nucleus may have dissimilar biosynthetic pathways and different biological activity. They are derived from l-phenylalanine, l-tyrosine, anthranilic acid or acetate, l-histidine, l-ornithine, nicotinic acid, and l-lysine. Apart from other types of alkaloids, indole, tropane, and isoquinoline alkaloids are very important. People from all over the world are using them in their everyday life. Alkaloids can also have an animal origin, which may be endogenous or exogenous. This chapter highlights the phytochemistry of the main representatives among the diverse group of alkaloids. This chapter also focuses on their extraction, purification, fractionation, identification, and quantification procedures. A fundamental understanding of the biological activity of important alkaloids is also highlighted in this chapter. With the potential of revealing new compounds and diverse pharmacological properties, alkaloids still embrace a great potential for the future of drug discovery.


title: A time-trend ecological study for identifying flood-sensitive infectious diseases in Guangxi, China from 2005 to 2012

text: Abstract Background Flood-related damage can be very severe and include health effects. Among those health impacts, infectious diseases still represent a significant public health problem in China. However, there have been few studies on the identification of the spectrum of infectious diseases associated with floods in one area. This study aimed to quantitatively identify sensitive infectious diseases associated with floods in Guangxi, China. Methods A time-trend ecological design was conducted. A descriptive analysis was first performed to exclude infectious diseases with low incidence from 2005 to 2012 in ten study sites of Guangxi. The Wilcoxon rank-sum test was applied to examine the difference in the ten-day attack rate of infectious diseases between the exposure and control periods with different lagged effects. Negative binomial, zero-inflated Poisson and zero-inflated negative binomial models were used to examine the relationship and odd ratios (ORs) of the risk of floods on infectious diseases of preliminary screening. Results A total of 417,271 infectious diseases were notified. There were 11 infectious diseases associated with floods in the preliminary screening process for flood-sensitive infectious diseases. The strongest effect was shown with a 0–9 ten-day lag in different infectious diseases. Multivariate analysis showed that floods were significantly associated with an increased the risk of bacillary dysentery (odds ratio (OR) = 1.268, 95% confidence interval (CI): 1.072–1.500), acute haemorrhagic conjunctivitis (AHC, OR = 3.230, 95% CI: 1.976–5.280), influenza A (H1N1) (OR = 1.808, 95% CI: 1.721–1.901), tuberculosis (OR = 1.200, 95% CI: 1.036–1.391), influenza (OR = 2.614, 95% CI: 1.476–4.629), Japanese encephalitis (OR = 2.334, 95% CI: 1.119–4.865), and leptospirosis (OR = 1.138, 95% CI: 1.075–1.205), respectively. Conclusion The spectrum of infectious diseases which are associated with floods are bacillary dysentery, AHC, influenza A (H1N1), tuberculosis, influenza, Japanese encephalitis and leptospirosis in Guangxi. Floods can result in differently increased risk of these diseases, and public health action should be taken to control a potential risk of these diseases after floods.


docid: wytlfffq

title: Feeding sentinels: Logics of care and biosecurity in farms and labs

text: This article compares the treatment of living beings (unvaccinated chickens and infected cells) considered as sentinel devices in a farm and in a lab in Hong Kong. Sentinel devices are defined as living beings posted on a boundary from which they send signals of invisible threats. The ethnography looks at how they transform differences between ordinary lives and lives exposed, between good death and bad death, through the practices of those who feed them. In farms and labs exposed to Avian Influenza viruses, the logic of biosecurity intersects with a logic of care, blurring the distinction between self and other, friend and enemy through aesthetic judgments concerning what is a ‘good death’. Metabolism and immunity are redefined when sentinels are fed to produce clear signals of the mutations of viruses.


Reply to Lipsitch


title: Downstream Ribosomal Entry for Translation of Coronavirus TGEV Gene 3b

text: Abstract Gene 3b (ORF 3b) in porcine transmissible gastroenteritis coronavirus (TGEV) encodes a putative nonstructural polypeptide of 27.7 kDa with unknown function that during translation in vitro is capable of becoming a glycosylated integral membrane protein of 31 kDa. In the virulent Miller strain of TGEV, ORF 3b is 5′-terminal on mRNA 3–1 and is presumably translated following 5′ cap-dependent ribosomal entry. For three other strains of TGEV, the virulent British FS772/70 and Taiwanese TFI and avirulent Purdue-116, mRNA species 3–1 is not made and ORF 3b is present as a non-overlapping second ORF on mRNA 3. ORF 3b begins at base 432 on mRNA 3 in Purdue strain. In vitro expression of ORF 3b from Purdue mRNA 3-like transcripts did not fully conform to a predicted leaky scanning pattern, suggesting ribosomes might also be entering internally. With mRNA 3-like transcripts modified to carry large ORFs upstream of ORF 3a, it was demonstrated that ribosomes can reach ORF 3b by entering at a distant downstream site in a manner resembling ribosomal shunting. Deletion analysis failed to identify a postulated internal ribosomal entry structure (IRES) within ORF 3a. The results indicate that an internal entry mechanism, possibly in conjunction with leaky scanning, is used for the expression of ORF 3b from TGEV mRNA 3. One possible consequence of this feature is that ORF 3b might also be expressed from mRNAs 1 and 2.


title: 15 Diffuse Air Space Opacities

text: Abstract Diffuse bilateral confluent air space opacities with air bronchograms may result from alveolar edema, pneumonia, or hemorrhage. Associated findings such as cardiac enlargement and pleural effusions help confirm the diagnosis of congestive heart failure; clinical findings of high fever, elevated white blood count, and productive cough favor pneumonia; and a history of hemoptysis may confirm pulmonary hemorrhage. This appearance is also seen in noncardiac edema from a variety of causes, including near-drowning, drug reactions, or acute respiratory distress syndrome. Pulmonary alveolar proteinosis is one of the few chronic diseases that causes this pattern.


title: Chapter 1 Introduction to Virus Origins and Their Role in Biological Evolution

text: Abstract Viruses are extremely abundant and diverse parasites of cells. They might have arisen during an early phase of the evolution of life on Earth dominated by RNA or RNA-like macromolecules, or when a cellular world was already well established. The theories of the origin of life on Earth shed light on the possible origin of primitive viruses or virus-like genetic elements in our biosphere. Some features of present day viruses, notably error-prone replication, might be a consequence of the selective forces that mediated their ancestral origin. Two views on the role of viruses in our biosphere predominate: viruses considered as opportunistic, selfish elements, and viruses considered as active participants in the construction of the cellular world via lateral transfers of genes. These two models bear on considering viruses predominantly as disease agents or predominantly as cooperators in the shaping of differentiated cellular organisms.


title: Trends in 30-Day Readmission Rates for Medicare and Non-Medicare Patients in the Era of the Affordable Care Act

text: Abstract Background Temporal changes in the readmission rates for patient groups and conditions that were not directly under the purview of the Hospital Readmissions Reduction Program (HRRP) can help assess whether efforts to lower readmissions extended beyond targeted patients and conditions. Methods Using the Nationwide Readmissions Database (2010-2015), we assessed trends in all-cause readmission rates for 1 of the 3 HRRP conditions (acute myocardial infarction, heart failure, pneumonia) or conditions not targeted by the HRRP in age-insurance groups defined by age group (≥65 years or <65 years) and payer (Medicare, Medicaid, or private insurance). Results In the group aged ≥65 years, readmission rates for those covered by Medicare, Medicaid, and private insurance decreased annually for acute myocardial infarction (risk-adjusted odds ratio [OR; 95% confidence interval] among Medicare patients, 0.94 [0.94-0.95], among Medicaid patients, 0.93 [0.90-0.97], and among patients with private-insurance, 0.95 [0.93-0.97]); heart failure (ORs, 0.96 [0.96-0.97], 0.96 [0.94-0.98], and 0.97 [0.96-0.99], for the 3 payers, respectively), and pneumonia (ORs, 0.96 [0.96-0.97), 0.94 [0.92-0.96], and 0.96 [0.95-0.97], respectively). Readmission rates also decreased in the group aged <65 years for acute myocardial infarction (ORs: Medicare 0.97 [0.96-0.98], Medicaid 0.94 [0.92-0.95], and private insurance 0.93 [0.92-0.94]), heart failure (ORs, 0.98 [0.97-0.98]: 0.96 [0.96-0.97], and 0.97 [0.95-0.98], for the 3 payers, respectively), and pneumonia (ORs, 0.98 [0.97-0.99], 0.98 [0.97-0.99], and 0.98 [0.97-1.00], respectively). Further, readmission rates decreased significantly for non-target conditions. Conclusions There appears to be a systematic improvement in readmission rates for patient groups beyond the population of fee-for-service, older, Medicare beneficiaries included in the HRRP.


title: Management of hypertension in COVID-19

text: The ACE2 receptor plays a central role in severe acute respiratory syndrome coronavirus 2 host cell entry and propagation. It has therefore been postulated that angiotensin converting enzyme inhibitors and angiotensin receptor blockers may upregulate ACE2 expression and thus increase susceptibility to infection. We suggest that alternative anti-hypertensive agents should be preferred among individuals who may be exposed to this increasingly common and potentially lethal virus.


title: Structure of the glycoprotein gene of sonchus yellow net virus, a plant rhabdovirus

text: Abstract The nucleotide sequence of the glycoprotein (G) gene of sonchus yellow net virus (SYNV), a plant rhabdovirus, was determined from viral genomic and mRNA cDNA clones. The G cistron is 2045 nucleotides (nt) long and the G protein mRNA open reading frame (ORF), as determined from the cDNA sequence, contains 1896 nt and encodes a protein of 632 amino acids. Immunoblots with antibodies elicited against the purified glycoprotein from virus particles reacted with a fusion protein produced in Escherichia coli, indicating that the cloned ORF encodes the G protein. The 5′ end of the G protein mRNA corresponds to nt 5111, relative to the 3′ end of the viral (minus sense) genome, as determined by primer extension from mRNA isolated from infected plants, and extends to nt position 7155 on the genomic RNA. A 34-nt untranslated 5′ leader sequence and a 115-nt untranslated 3′ end flank the ORF on the mRNA. The gene junctions on either side of the G gene on the genomic RNA are identical to those previously described for other SYNV genes and are similar to sequences separating genes of animal rhabdoviruses. The predicted molecular weight of the G protein is 70,215 Da, a value less than the 77,000 Da estimated for the glycosylated G protein from virus particles. The deduced amino acid sequence of the SYNV G protein shares little direct relatedness with the G proteins of other rhabdoviruses, but appears to contain a similar signal sequence, a transmembrane anchor domain, and glycosylation signals. In addition, the SYNV G protein contains a putative nuclear targeting site near the carboxy terminus, which may be involved in transit to the nuclear membrane prior to morphogenesis.


title: Middle east respiratory syndrome corona virus spike glycoprotein suppresses macrophage responses via DPP4-mediated induction of IRAK-M and PPARγ

text: Middle East Respiratory Syndrome Corona Virus (MERS-CoV) is transmitted via the respiratory tract and causes severe Acute Respiratory Distress Syndrome by infecting lung epithelial cells and macrophages. Macrophages can readily recognize the virus and eliminate it. MERS-CoV infects cells via its Spike (S) glycoprotein that binds on Dipeptidyl-Peptidase 4 (DPP4) receptor present on macrophages. Whether this Spike/DPP4 association affects macrophage responses remains unknown. Herein we demonstrated that infection of macrophages with lentiviral particles pseudotyped with MERS-CoV S glycoprotein results in suppression of macrophage responses since it reduced the capacity of macrophages to produce TNFa and IL-6 in naive and LPS-activated THP-1 macrophages and augmented LPS-induced production of the immunosuppressive cytokine IL-10. MERS-CoV S glycoprotein induced the expression of the negative regulator of TLR signaling IRAK-M as well as of the transcriptional repressor PPARγ. Inhibition of DPP4 by its inhibitor sitagliptin or siRNA abrogated the effects of MERS-CoV S glycoprotein on IRAK-M, PPARγ and IL-10, confirming that its immunosuppressive effects were mediated by DPP4 receptor. The effect was observed both in THP-1 macrophages and human primary peripheral blood monocytes. These findings support a DPP4-mediated suppressive action of MERS-CoV in macrophages and suggest a potential target for effective elimination of its pathogenicity.


title: Do psychiatric patients experience more psychiatric symptoms during COVID-19 pandemic and lockdown? A Case-Control Study with Service and Research Implications for Immunopsychiatry

text: Abstract This study aimed to assess and compare the immediate stress and psychological impact experienced by people with and without psychiatric illnesses during the peak of 2019 coronavirus disease (COVID-19) epidemic with strict lockdown measures. Seventy-six psychiatric patients and 109 healthy control subjects were recruited from Chongqing, China and completed a survey on demographic data, physical symptoms during the past 14 days and a range of psychiatric symptoms using the Impact of Event Scale- Revised (IES-R), Depression, Anxiety and Stress Scale (DASS-21) and Insomnia Severity Index (ISI). IES-R measures PTSD symptoms in survivorship after an event. DASS -21 is based on tripartite model of psychopathology that comprise a general distress construct with distinct characteristics. The mean IES-R, DASS-21 anxiety, depression and stress subscale and ISI scores were higher in psychiatric patients than healthy controls (p<0.001). Serious worries about their physical health, anger and impulsivity and intense suicidal ideation were significantly higher in psychiatric patients than healthy controls (p<0.05). More than one-third of psychiatric patients might fulfil the diagnostic criteria post-traumatic stress disorder (PTSD). More than one-quarter of psychiatric patients suffered from moderately severe to severe insomnia. Respondents who reported no change, poor or worse physical health status and had a psychiatric illness were significantly more likely to have higher mean IES-R, DASS depression, anxiety and stress subscale scores and ISI scores (p<0.05). This study confirms the severity of negative psychological impact on psychiatric patients during the COVID-19 epidemic with strict lockdown measures. Understanding the psychological impact on psychiatric patients during the COVID-19 pandemic has the potential to provide insight into how to develop a new immunopsychiatry service. Further research is required to compare pro-inflammatory cytokines between psychiatric patients and healthy controls during the pandemic.


title: Food-borne diseases — The challenges of 20years ago still persist while new ones continue to emerge

text: Abstract The burden of diseases caused by food-borne pathogens remains largely unknown. Importantly data indicating trends in food-borne infectious intestinal disease is limited to a few industrialised countries, and even fewer pathogens. It has been predicted that the importance of diarrhoeal disease, mainly due to contaminated food and water, as a cause of death will decline worldwide. Evidence for such a downward trend is limited. This prediction presumes that improvements in the production and retail of microbiologically safe food will be sustained in the developed world and, moreover, will be rolled out to those countries of the developing world increasingly producing food for a global market. In this review evidence is presented to indicate that the microbiological safety of food remains a dynamic situation heavily influenced by multiple factors along the food chain from farm to fork. Sustaining food safety standards will depend on constant vigilance maintained by monitoring and surveillance but, with the rising importance of other food-related issues, such as food security, obesity and climate change, competition for resources in the future to enable this may be fierce. In addition the pathogen populations relevant to food safety are not static. Food is an excellent vehicle by which many pathogens (bacteria, viruses/prions and parasites) can reach an appropriate colonisation site in a new host. Although food production practices change, the well-recognised food-borne pathogens, such as Salmonella spp. and Escherichia coli, seem able to evolve to exploit novel opportunities, for example fresh produce, and even generate new public health challenges, for example antimicrobial resistance. In addition, previously unknown food-borne pathogens, many of which are zoonotic, are constantly emerging. Current understanding of the trends in food-borne diseases for bacterial, viral and parasitic pathogens has been reviewed. The bacterial pathogens are exemplified by those well-recognized by policy makers; i.e. Salmonella, Campylobacter, E. coli and Listeria monocytogenes. Antimicrobial resistance in several bacterial food-borne pathogens (Salmonella, Campylobacter, Shigella and Vibrio spp., methicillin resistant Staphylcoccus aureas, E. coli and Enterococci) has been discussed as a separate topic because of its relative importance to policy issues. Awareness and surveillance of viral food-borne pathogens is generally poor but emphasis is placed on Norovirus, Hepatitis A, rotaviruses and newly emerging viruses such as SARS. Many food-borne parasitic pathogens are known (for example Ascaris, Cryptosporidia and Trichinella) but few of these are effectively monitored in foods, livestock and wildlife and their epidemiology through the food-chain is poorly understood. The lessons learned and future challenges in each topic are debated. It is clear that one overall challenge is the generation and maintenance of constructive dialogue and collaboration between public health, veterinary and food safety experts, bringing together multidisciplinary skills and multi-pathogen expertise. Such collaboration is essential to monitor changing trends in the well-recognised diseases and detect emerging pathogens. It will also be necessary understand the multiple interactions these pathogens have with their environments during transmission along the food chain in order to develop effective prevention and control strategies.


title: Genetic deletion of Sphk2 confers protection against Pseudomonas aeruginosa mediated differential expression of genes related to virulent infection and inflammation in mouse lung

text: BACKGROUND: Pseudomonas aeruginosa (PA) is an opportunistic Gram-negative bacterium that causes serious life threatening and nosocomial infections including pneumonia. PA has the ability to alter host genome to facilitate its invasion, thus increasing the virulence of the organism. Sphingosine-1- phosphate (S1P), a bioactive lipid, is known to play a key role in facilitating infection. Sphingosine kinases (SPHK) 1&2 phosphorylate sphingosine to generate S1P in mammalian cells. We reported earlier that Sphk2(−/−) mice offered significant protection against lung inflammation, compared to wild type (WT) animals. Therefore, we profiled the differential expression of genes between the protected group of Sphk2(−/−) and the wild type controls to better understand the underlying protective mechanisms related to the Sphk2 deletion in lung inflammatory injury. Whole transcriptome shotgun sequencing (RNA-Seq) was performed on mouse lung tissue using NextSeq 500 sequencing system. RESULTS: Two-way analysis of variance (ANOVA) analysis was performed and differentially expressed genes following PA infection were identified using whole transcriptome of Sphk2(−/−) mice and their WT counterparts. Pathway (PW) enrichment analyses of the RNA seq data identified several signaling pathways that are likely to play a crucial role in pneumonia caused by PA such as those involved in: 1. Immune response to PA infection and NF-κB signal transduction; 2. PKC signal transduction; 3. Impact on epigenetic regulation; 4. Epithelial sodium channel pathway; 5. Mucin expression; and 6. Bacterial infection related pathways. Our genomic data suggests a potential role for SPHK2 in PA-induced pneumonia through elevated expression of inflammatory genes in lung tissue. Further, validation by RT-PCR on 10 differentially expressed genes showed 100% concordance in terms of vectoral changes as well as significant fold change. CONCLUSION: Using Sphk2(−/−) mice and differential gene expression analysis, we have shown here that S1P/SPHK2 signaling could play a key role in promoting PA pneumonia. The identified genes promote inflammation and suppress others that naturally inhibit inflammation and host defense. Thus, targeting SPHK2/S1P signaling in PA-induced lung inflammation could serve as a potential therapy to combat PA-induced pneumonia.


title: Handwashing and risk of respiratory infections: a quantitative systematic review

text: Objective To determine the effect of handwashing on the risk of respiratory infection. Methods We searched PubMed, CAB Abstracts, Embase, Web of Science, and the Cochrane library for articles published before June 2004 in all languages. We had searched reference lists of all primary and review articles. Studies were included in the review if they reported the impact of an intervention to promote hand cleansing on respiratory infections. Studies relating to hospital‐acquired infections, long‐term care facilities, immuno‐compromised and elderly people were excluded. We independently evaluated all studies, and inclusion decisions were reached by consensus. From a primary list of 410 articles, eight interventional studies met the eligibility criteria. Results All eight eligible studies reported that handwashing lowered risks of respiratory infection, with risk reductions ranging from 6% to 44% [pooled value 24% (95% CI 6–40%)]. Pooling the results of only the seven homogenous studies gave a relative risk of 1.19 (95% CI 1.12%–1.26%), implying that hand cleansing can cut the risk of respiratory infection by 16% (95% CI 11–21%). Conclusions Handwashing is associated with lowered respiratory infection. However, studies were of poor quality, none related to developing countries, and only one to severe disease. Rigorous trials of the impact of handwashing on acute respiratory tract infection morbidity and mortality are urgently needed, especially in developing countries.


title: The use of a multiplex real-time PCR assay for diagnosing acute respiratory viral infections in children attending an emergency unit

text: Abstract Background The use of a multiplex molecular technique to identify the etiological pathogen of respiratory viral infections might be a support as clinical signs are not characteristic. Objectives The aim of the study was to evaluate a multiplex molecular real-time assay for the routine diagnosis of respiratory viruses, to analyze the symptoms associated with the pathogens detected and to determine the spread of virus during the period. Study design Respiratory samples were collected from children presenting with respiratory symptoms and attending the emergency unit during the 2010–2011 winter seasons. Samples were tested with the multiplex RespiFinder® 15 assay (PathoFinder™) which potentially detects 15 viruses. Results 857 (88.7%) of the 966 samples collected from 914 children were positive for one (683 samples) or multiple viruses (174 samples). The most prevalent were the respiratory syncytial virus (39.5%) and the rhinovirus (24.4%). Influenza viruses were detected in 139 (14.4%) samples. Adenovirus was detected in 93 (9.6%) samples, coronaviruses in 88 (9.1%), metapneumovirus in 51 (5.3%) and parainfluenzae in 47 (4.9%). Rhinovirus (40%) was the most prevalent pathogen in upper respiratory tract infections while respiratory syncytial virus (49.9%) was the most prevalent in lower respiratory tract infections. Co-infections were associated with severe respiratory symptoms. Conclusion The multiplex assay detected clinically important viruses in a single genomic test and thus will be useful for detecting several viruses causing respiratory tract disorders.


title: THE EXPANDING REGULATORY NETWORK OF STING-MEDIATED SIGNALING

text: The identification and characterization of DNA-sensing pathways has been a subject of intensive investigation for the last decade. This interest, in part, is supported by the fact that the main outcome of DNA-responses is production of type I interferon (IFN-I), which, if produced in excessive amounts, leads to various pathologies. STING (Stimulator of Interferon Genes) is positioned in the center of these responses and is activated either via direct sensing of second messengers or via interaction with upstream sensors of dsDNA. STING mediates responses to pathogens as well as host-derived DNA and is, therefore, linked to various autoimmune diseases, cancer predisposition and ageing. Recent mouse models of DNA damage showed the adaptor STING to be crucial for heightened resting levels of IFN-I. In this review, we will focus on recent advances in understanding the regulation of STING-signaling and identification of its novel components.


COVID-19: An update from England's high consequence infectious diseases intensive care unit leads.


title: Gene- and Viral-Based Therapies for Brain Tumors

text: Summary Advances in understanding and controlling genes and their expression have set the stage to alter genetic material to fight or prevent disease with brain tumors being among one of the first human malignancies to be targeted by gene therapy. All proteins are coded for by DNA and most neoplastic diseases ultimately result from the expression or lack thereof with one or more proteins (e.g., coded by oncogenes or tumor suppressor genes, respectively). In theory, therefore, diseases could be treated by expression of the appropriate protein in the affected cells. Gene therapy is an experimental treatment that involves introducing genetic material (DNA or RNA) into cells, and it has made important advances in the past decade. Within this short time span, it has moved from the conceptual laboratory research stage to clinical translational trials for brain tumors. The most efficient approaches for gene delivery are based on viral vectors, which have been proven relatively safe in the CNS, despite occasional cases of morbidity and death in non-neurosurgical trials. However, the human response to various viral vectors can not be predicted in a reliable manner from animal experimentation, nor can size, consistency, and extent of experimental brain tumors in mouse models reflect the large, necrotic, infiltrative nature of malignant gliomas. Furthermore, the problem of delivering genetic vectors into solid brain tumors and the efficiency in situ gene transfer remains one of the most significant hurdles in gene therapy.


docid: uruklzls

title: Epidemiological, clinical, and immunological features of a cluster of COVID-19 contracted hemodialysis patients

text: BACKGROUND: The outbreak of highly contagious COVID-19 has posed a serious threat to human life and health, especially for those with underlying diseases. However, the impact of COVID-19 epidemic on HD center and HD patients has not been reported. METHODS: We reviewed the whole course of the COVID-19 in the HD center of Renmin Hospital, Wuhan University (from January 14, 2020 till March 12, 2020). We compared the clinical manifestation and immune profiles among different patient groups with healthy individuals. RESULTS: 42 out of 230 HD patients (18.26%) and 4 out of 33 medical staff (12.12%) were diagnosed with COVID-19 during the study period. 15 HD patients (6.52%), including 10 COVID-19 diagnosed, died. Only 2 deaths of the COVID-19 HD patients were associated with pneumonia/lung failure, others were ascribed to cardiovascular/cerebrovascular diseases or hyperkalemia. Except for 3 patients who were admitted to ICU for severe condition (8.11%), including 2 dead, most COVID-19 diagnosed patients presented mild or non-respiratory symptoms. The flow cytometric analysis of peripheral blood showed that multiple lymphocyte populations in HD patients were significantly decreased. HD patients with COVID-19 even displayed more remarkable reduction of serum inflammatory cytokines than other COVID-19 patients. CONCLUSIONS: Compared with the general population, HD patients and health care professionals are the highly susceptible population and HD centers are high risk area during the outbreak. A majority of HD Patients with COVID-19 exhibited mild clinical symptoms and did not progress to severe pneumonia likely due to the impaired cellular immune function and incapability of mounting cytokines storm. More attention should be paid to prevent cardiovascular events, which may be the collateral impacts of COVID-19 epidemic on HD patients.


Zerebrovaskuläre Komplikationen bei Patienten mit COVID-19


title: Other Respiratory Viruses Are Important Contributors to Adult Respiratory Hospitalizations and Mortality Even During Peak Weeks of the Influenza Season

text: BACKGROUND: During peak weeks of seasonal influenza epidemics, severe respiratory infections without laboratory confirmation are typically attributed to influenza. METHODS: In this prospective study, specimens and demographic and clinical data were collected from adults admitted with respiratory symptoms to 4 hospitals during the 8–10 peak weeks of 2 influenza seasons. Specimens were systematically tested for influenza and 13 other respiratory viruses (ORVs) by using the Luminex RVP FAST assay. RESULTS: At least 1 respiratory virus was identified in 46% (21% influenza, 25% noninfluenza; 2% coinfection) of the 286 enrolled patients in 2011–2012 and in 62% (46% influenza, 16% noninfluenza; 3% coinfection) of the 396 enrolled patients in 2012–2013. Among patients aged ≥75 years, twice as many ORVs (32%) as influenza viruses (14%) were detected in 2011–2012. During both seasons, the most frequently detected ORVs were enteroviruses/rhinoviruses (7%), respiratory syncytial virus (6%), human metapneumovirus (5%), coronaviruses (4%), and parainfluenza viruses (2%). Disease severity was similar for influenza and ORVs during both seasons. CONCLUSIONS: Although ORV contribution relative to influenza varies by age and season, during the peak weeks of certain influenza seasons, ORVs may be a more frequent cause of elderly hospitalization than influenza.


title: The Role of Myeloid Cell Activation and Arginine Metabolism in the Pathogenesis of Virus-Induced Diseases

text: When an antiviral immune response is generated, a balance must be reached between two opposing pathways: the production of proinflammatory and cytotoxic effectors that drive a robust antiviral immune response to control the infection and regulators that function to limit or blunt an excessive immune response to minimize immune-mediated pathology and repair tissue damage. Myeloid cells, including monocytes and macrophages, play an important role in this balance, particularly through the activities of the arginine-hydrolyzing enzymes nitric oxide synthase 2 (Nos2; iNOS) and arginase 1 (Arg1). Nitric oxide (NO) production by iNOS is an important proinflammatory mediator, whereas Arg1-expressing macrophages contribute to the resolution of inflammation and wound repair. In the context of viral infections, expression of these enzymes can result in a variety of outcomes for the host. NO has direct antiviral properties against some viruses, whereas during other virus infections NO can mediate immunopathology and/or inhibit the antiviral immune response to promote chronic infection. Arg1 activity not only has important wound healing functions but can also inhibit the antiviral immune response during some viral infections. Thus, depending on the specific virus and the tissue(s) involved, the activity of both of these arginine-hydrolyzing enzymes can either exacerbate or limit the severity of virus-induced disease. In this review, we will discuss a variety of viral infections, including HIV, SARS-CoV, LCMV, HCV, RSV, and others, where myeloid cells influence the control and clearance of the virus from the host, as well as the severity and resolution of tissue damage, via the activities of iNOS and/or Arg1. Clearly, monocyte/macrophage activation and arginine metabolism will continue to be important areas of investigation in the context of viral infections.


COVID-19 and globalization


docid: lttavvly

title: Extended ORF8 Gene Region Is Valuable in the Epidemiological Investigation of Severe Acute Respiratory Syndrome–Similar Coronavirus

text: Severe acute respiratory syndrome coronavirus (SARS-CoV) was discovered as a novel pathogen in the 2002–2003 SARS epidemic. The emergence and disappearance of this pathogen have brought questions regarding its source and evolution. Within the genome sequences of 281 SARS-CoVs, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and SARS-related CoVs (SARSr-CoVs), a ~430 bp genomic region (from 27 701 bp to 28 131 bp in AY390556.1) with regular variations was investigated. This ~430 bp region overlaps with the ORF8 gene and is prone to deletions and nucleotide substitutions. Its complexity suggested the need for a new genotyping method for coronaviruses related to SARS-similar coronaviruses (SARS-CoV, SARSr-CoV, and SARS-CoV-2). Bat SARSr-CoV presented 3 genotypes, of which type 0 is only seen in bat SARSr-CoV, type I is present in SARS in the early phase, and type II is found in all SARS-CoV-2. This genotyping also shows potential usage in distinguishing the SARS-similar coronaviruses from different hosts and geographic areas. This genomic region has important implications for predicting the epidemic trend and studying the evolution of coronavirus.


title: The autopsy at the time of SARS-CoV-2: Protocol and lessons

text: A new viral disease named COVID-19 has recently turned into a pandemic. Compared to a common viral pneumonia it may evolve in an atypical way, causing the rapid death of the patient. For over two centuries, autopsy has been recognized as a fundamental diagnostic technique, particularly for new or little-known diseases. To date, it is often considered obsolete giving the inadequacy to provide samples of a quality appropriate to the sophisticated diagnostic techniques available today. This is probably one of the reasons why during this pandemic autopsies were often requested only in few cases, late and discouraged, if not prohibited, by more than one nation. This is in contrast with our firm conviction: to understand the unknown we must look at it directly and with our own eyes. This has led us to implement an autopsy procedure that allows the beginning of the autopsy shortly after death (within 1–2 h) and its rapid execution, also including sampling for ultrastructural and molecular investigations. In our experience, the tissue sample collected for diagnosis and research were of quality similar to biopsy or surgical resections. This procedure was performed ensuring staff and environmental safety. We want to propose our experience, our main qualitative results and a few general considerations, hoping that they can be an incentive to use autopsy with a new procedure adjusted to match the diagnostic challenges of the third millennium.


docid: okmkgsbr

title: Influenza virus infection affects insulin signaling, fatty acid-metabolizing enzyme expressions, and the tricarboxylic acid cycle in mice

text: Although the severity of influenza virus infections has been associated with host energy metabolism, the related mechanisms have not yet been clarified. Here we examined the effects of influenza virus infection on host energy metabolism in mice. After infecting mice with intranasal applications of 500 plaque-forming units of A/Puerto Rico/8/34 (H1N1; PR8) virus, the serum levels of most intermediates in the tricarboxylic acid (TCA) cycle and related metabolic pathways were significantly reduced. These data suggest that substrate supply to the TCA cycle is reduced under these conditions, rather than specific metabolic reactions being inhibited. Then, we focused on glucose and fatty acid metabolism that supply substrates to the TCA cycle. Akt phosphorylation following insulin injections was attenuated in the livers of PR8 virus-infected mice. Furthermore, glucose tolerance tests revealed that the PR8 virus-infected mice showed higher blood glucose levels than the vehicle-inoculated control mice. These results suggest that influenza virus infection impairs insulin signaling, which regulates glucose uptake. However, increases in the hepatic expressions of fatty acid-metabolizing enzymes suggest that fatty acids accumulate in liver cells of infected mice. Collectively, our data indicate that influenza virus infection dysregulates host energy metabolism. This line of investigation provides novel insights into the pathogenesis of influenza.


title: Walk-Through Screening Center for COVID-19: an Accessible and Efficient Screening System in a Pandemic Situation

text: With the ongoing novel coronavirus disease 2019 (COVID-19) pandemic, the number of individuals that need to be tested for COVID-19 has been rapidly increasing. A walk-through (WT) screening center using negative pressure booths that is inspired by the biosafety cabinet has been designed and implemented in Korea for easy screening of COVID-19 and for safe and efficient consultation for patients with fever or respiratory symptoms. Here, we present the overall concept, advantages, and limitations of the COVID-19 WT screening center. The WT center increases patient access to the screening clinics and adequately protects healthcare personnel while reducing the consumption of personal protective equipment. It can also increase the number of people tested by 9–10 fold. However, there is a risk of cross-infection at each stage of screening treatment, including the booths, and adverse reactions with disinfection of the booths. These limitations can be overcome using mobile technology and increasing the number of booths to reduce congestion inside the center, reducing booth volume for sufficient and rapid ventilation, and using an effective, harmless, and certified environmental disinfectant. A WT center can be implemented in other institutions and countries and modified depending on local needs to cope with the COVID-19 pandemic.


title: Unravelling the Myths of R(0) in Controlling the Dynamics of COVID-19 Outbreak: a Modelling Perspective

text: COVID-19 is an emerging and rapidly evolving pandemic around the world, which causes severe acute respiratory syndrome and results in substantial morbidity and mortality. To examine the transmission dynamics of COVID-19, we investigate the spread of this pandemic using Malaysia as a case study and investigate its interactions with some exogenous factors such as limited medical resources and false detection problems. To do this, we employ a simple epidemiological model and analyse this system using modelling and dynamical systems techniques. We discover some contrasting findings with respect to the observations of basic reproduction number: while it is observed that R(0) seems to provide a good description of transmission dynamic in simple pandemic scenarios, this quantity might mislead the assessment on the severity of pandemic when certain complexities such as limited medical resources and false detection problems are incorporated into the model. In particular, we observe the possibility of a COVID-19 pandemic through bistable behaviour, even when the basic reproduction number is less than unity. Based on these findings, we caution policy makers not to make their decisions solely based on the guidance of the basic reproduction number only, which clearly courting trouble.


title: COVID-19 and “Lockdown” in Organ transplantation in the UK

text: Abstract Recent outbreak of Coronavirus (COVID-19) has impacted the health services globally. The UK has experienced the second highest deaths in the world (after USA) of over 40,000 people due to COVID-19. In the beginning of March 2020, as a precaution most NHS hospital trust halted the organ transplant services due to outbreak of COVID-19 and completed ceased the live-donors facility. This has severely affected the waiting time especially for patients from ethnic minorities.


Transplantation of murine oligodendrocytes and JHMV-infected astrocytes into demyelinating lesions in the rat spinal cord


title: New Frontiers of Basic Science Research in Neurogenic Lower Urinary Tract Dysfunction

text: The lower urinary tract has two main functions, storage and elimination. The micturition reflex is one of the autonomic reflexes mediated by the spinobulbospinal reflex pathway that passes through the pontine micturition center. This reflex pathway is in turn modulated by higher centers in the cerebral cortex that are involved in the voluntary control of micturition. Due to the complexity of the neural control of lower urinary tract, micturition is sensitive to numerous injuries, such as spinal cord injury, cerebral infarction, Parkinson’s disease, multiple sclerosis and spina bifida, which result in various types of neurogenic lower urinary tract dysfunction. Studies in animals for these diseases involved in the central nervous system indicate that the lower urinary tract dysfunction is dependent in part on plasticity of the neural pathways controlling the lower urinary tract. Reflex plasticity is also associated with changes in the properties of ion channels, receptors, and numerous mediators. These animal models may help to investigate the mechanism involved in the genesis of pathological conditions as well as the plasticity in reflex pathways to the lower urinary tract after neurogenic lesions.