title: Regulation of V-ATPase Activity and Organelle pH by Phosphatidylinositol Phosphate Lipids

text: Luminal pH and the distinctive distribution of phosphatidylinositol phosphate (PIP) lipids are central identifying features of organelles in all eukaryotic cells that are also critical for organelle function. V-ATPases are conserved proton pumps that populate and acidify multiple organelles of the secretory and the endocytic pathway. Complete loss of V-ATPase activity causes embryonic lethality in higher animals and conditional lethality in yeast, while partial loss of V-ATPase function is associated with multiple disease states. On the other hand, many cancer cells increase their virulence by upregulating V-ATPase expression and activity. The pH of individual organelles is tightly controlled and essential for function, but the mechanisms for compartment-specific pH regulation are not completely understood. There is substantial evidence indicating that the PIP content of membranes influences organelle pH. We present recent evidence that PIPs interact directly with subunit isoforms of the V-ATPase to dictate localization of V-ATPase subpopulations and participate in their regulation. In yeast cells, which have only one set of organelle-specific V-ATPase subunit isoforms, the Golgi-enriched lipid PI(4)P binds to the cytosolic domain of the Golgi-enriched a-subunit isoform Stv1, and loss of PI(4)P binding results in mislocalization of Stv1-containing V-ATPases from the Golgi to the vacuole/lysosome. In contrast, levels of the vacuole/lysosome-enriched signaling lipid PI(3,5)P(2) affect assembly and activity of V-ATPases containing the Vph1 a-subunit isoform. Mutations in the Vph1 isoform that disrupt the lipid interaction increase sensitivity to stress. These studies have decoded “zip codes” for PIP lipids in the cytosolic N-terminal domain of the a-subunit isoforms of the yeast V-ATPase, and similar interactions between PIP lipids and the V-ATPase subunit isoforms are emerging in higher eukaryotes. In addition to direct effects on the V-ATPase, PIP lipids are also likely to affect organelle pH indirectly, through interactions with other membrane transporters. We discuss direct and indirect effects of PIP lipids on organelle pH, and the functional consequences of the interplay between PIP lipid content and organelle pH.


title: First report of Toxoplasma gondii seroprevalence in peafowls in Yunnan Province, Southwestern China

text: BACKGROUND: Toxoplasma gondii is an intracellular protozoan parasite infecting almost all warm-blooded animals, including birds, with a worldwide distribution. Surveys of T. gondii infection in wild birds have been reported extensively in the world, but little is known of T. gondii infection in peafowls worldwide. This study was performed to determine the seroprevalence of T. gondii infection in peafowls in Yunnan Province, southwestern China. METHODS: Sera from 277 peafowls, including 272 blue peafowls (Pavo cristatus) and 5 green peafowls (Pavo muticus) originated from two geographic areas in Yunnan Province were assayed for T. gondii antibodies using the modified agglutination test (MAT). RESULTS: Specific T. gondii antibodies were detected in 35 of 277 (12.64%) peafowls (MAT titer ≥ 1:5). Seropositive birds were found in both species, 33 in 272 blue peafowls and 2 in 5 green peafowls. There was no significant difference in T. gondii seroprevalence between the adolescent birds (6.74%) and the adult birds (6.67%) (P > 0.05). The geographical origins of peafowls was found to be highly associated with T. gondii infection in the present study, a statistically significant difference in T. gondii seropositivity was observed between peafowls from Kunming (31.08%) and those from Xishuangbanna Dai Autonomous Prefecture (5.91%) (OR = 10.956, 95% CI = 1.632-73.545, P = 0.014). Statistical analyses showed that there were no significant interactions between ages and geographical origins of peafowls (P > 0.05). CONCLUSIONS: The results of the present survey indicated that infection of peafowls with T. gondii is widespread in Yunnan Province, which has significant public health concerns and implications for prevention and control of toxoplamosis in this province. To our knowledge, this is the first seroprevalence report of T. gondii infection in China’s southwestern Yunnan Province.


title: Anti-varicella-zoster virus activity of cephalotaxine esters in vitro

text: Harringtonine (HT) and homoharringtonine (HHT), alkaloid esters isolated from the genus Cephalotaxus, exhibit antitumor activity. A semisynthetic HHT has been approved for treatment of chronic myelogenous leukemia. In addition to antileukemic activity, HT and HHT are reported to possess potent antiviral activity. In this study, we investigated the effects of HT and HHT on replication of varicella-zoster virus (VZV) in vitro. HT and HHT, but not their biologically inactive parental alkaloid cephalotaxine (CET), significantly inhibited replication of recombinant VZV-pOka luciferase. Furthermore, HT and HHT, but not CET, strongly induced down-regulation of VZV lytic genes and exerted potent antiviral effects against a VZV clinical isolate. The collective data support the utility of HT and HHT as effective antiviral candidates for treatment of VZV-associated diseases.


title: The First 75 Days of Novel Coronavirus (SARS-CoV-2) Outbreak: Recent Advances, Prevention, and Treatment

text: The recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, previously known as 2019-nCoV) outbreak has engulfed an unprepared world amidst a festive season. The zoonotic SARS-CoV-2, believed to have originated from infected bats, is the seventh member of enveloped RNA coronavirus. Specifically, the overall genome sequence of the SARS-CoV-2 is 96.2% identical to that of bat coronavirus termed BatCoV RaTG13. Although the current mortality rate of 2% is significantly lower than that of SARS (9.6%) and Middle East respiratory syndrome (MERS) (35%), SARS-CoV-2 is highly contagious and transmissible from human to human with an incubation period of up to 24 days. Some statistical studies have shown that, on average, one infected patient may lead to a subsequent 5.7 confirmed cases. Since the first reported case of coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 on December 1, 2019, in Wuhan, China, there has been a total of 60,412 confirmed cases with 1370 fatalities reported in 25 different countries as of February 13, 2020. The outbreak has led to severe impacts on social health and the economy at various levels. This paper is a review of the significant, continuous global effort that was made to respond to the outbreak in the first 75 days. Although no vaccines have been discovered yet, a series of containment measures have been implemented by various governments, especially in China, in the effort to prevent further outbreak, whilst various medical treatment approaches have been used to successfully treat infected patients. On the basis of current studies, it would appear that the combined antiviral treatment has shown the highest success rate. This review aims to critically summarize the most recent advances in understanding the coronavirus, as well as the strategies in prevention and treatment.


COVID-19 and Argumentum ad ignorantiam or “not everything goes”()


title: Quantifying tetrahedral adduct formation and stabilization in the cysteine and the serine proteases

text: Abstract Two new papain inhibitors have been synthesized where the terminal α-carboxyl groups of Z-Phe-Ala-COOH and Ac-Phe-Gly-COOH have been replaced by a proton to give Z-Phe-Ala-H and Ac-Phe-Gly-H. We show that for papain, replacing the terminal carboxylate group of a peptide inhibitor with a hydrogen atom decreases binding 3–4 fold while replacing an aldehyde or glyoxal group with a hydrogen atom decreases binding by 300,000–1,000,000 fold. Thiohemiacetal formation by papain with aldehyde or glyoxal inhibitors is shown to be ~10,000 times more effective than hemiacetal or hemiketal formation with chymotrypsin. It is shown using effective molarities, that for papain, thiohemiacetal stabilization is more effective with aldehyde inhibitors than with glyoxal inhibitors. The effective molarity obtained when papain is inhibited by an aldehyde inhibitor is similar to the effective molarity obtained when chymotrypsin is inhibited by glyoxal inhibitors showing that both enzymes can stabilize tetrahedral adducts by similar amounts. Therefore the greater potency of aldehyde and glyoxal inhibitors with papain is not due to greater thiohemiacetal stabilization by papain compared to the hemiketal and hemiacetal stabilization by chymotrypsin, instead it reflects the greater intrinsic reactivity of the catalytic thiol group of papain compared to the catalytic hydroxyl group of chymotrypsin. It is argued that while the hemiacetals and thiohemiacetals formed with the serine and cysteine proteases respectively can mimic the catalytic tetrahedral intermediate they are also analogues of the productive and non-productive acyl intermediates that can be formed with the cysteine and serine proteases.


title: Multiattribute evaluation of two simple tests for the detection of Cryptosporidium parvum in calf faeces

text: Abstract There is a need for simple and inexpensive diagnostic and screening tests for the detection of Cryptosporidium parvum infection in calves. A sucrose wet mount test and a lateral immunochromatography test were evaluated for epidemiological sensitivity and specificity, cost per test, simplicity, test time and ease of batching. Polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) of the Cryptosporidium oocyst wall protein (COWP) gene locus, with gel electrophoresis, was used as a gold standard. Cohen's kappa statistic of agreement (к) between the Ontario Veterinary College (OVC) sucrose wet mount test and COWP PCR–RFLP was 0.82, and the sensitivity and specificity of the OVC sucrose wet mount test were 88.6% and 93.8%, respectively. The sensitivity and specificity of the lateral immunochromatography test were 78.3% and 93.3%, respectively, and agreement between this test and PCR–RFLP was good (к =0.73). There was substantial agreement between the OVC sucrose wet mount test and the lateral immunochromatography test (к =0.84). Both tests were inexpensive and easy to use; however, the lateral immunochromatography test was faster and simpler to perform than the sucrose wet mount test, and was generally more user-friendly. These tests provide practitioners and researchers with cheap, quick and accurate methods of detecting C. parvum infection in young calves.


title: Adverse consequences of vaccination

text: The importance of adverse effects from vaccination must not be overstated. Vaccine benefits greatly exceed any risks from the procedure. Neither must they be minimized. Unnecessary vaccination must be discouraged. Hypersensitivity reactions to vaccine components are real and must be guarded against. Residual virulence, although a concern tends to be more a hypothetical than a real problem. Progressive improvements in animal vaccines have significantly reduced the chances of adverse effects occurring, although some issues persist. One such example is injection-site sarcomas in cats. Another issue is the influence of animal size on the prevalence of adverse events in dogs.


title: Large-scale de novo DNA synthesis: technologies and applications

text: For over 60 years, the synthetic production of new DNA sequences has helped researchers understand and engineer biology. Here we summarize methods and caveats for the de novo synthesis of DNA, with particular emphasis on recent technologies that allow for large-scale and low-cost production. In addition, we discuss emerging applications enabled by large-scale de novo DNA constructs, as well as the challenges and opportunities that lie ahead.


title: A targeted response to the COVID‐19 pandemic: analysing effectiveness of remote consultations for triage and management of routine dermatology referrals

text: New patient referrals from primary care into dermatology services usually enter via one of three routes: (i) 2 week wait for suspected serious skin malignancies, (ii) routine non‐urgent cases and (iii) emergency referrals (via an on call service). All these patients are assessed via a face‐to‐face consultation, after various waiting times depending on their urgency.


title: Considerations and strategies in the organisation of obstetric anaesthesia care during the 2019 COVID-19 outbreak in Singapore

text: • Identifying ‘high-infection risk’ parturients is challenging in the COVID-19 outbreak. • A multidisciplinary approach is required to provide obstetric anaesthesia services. • Protocols for labour analgesia and caesarean delivery allow safe provision of care. • Infection control resource management allows for the allocation of finite resources. • Organisational changes are required to respond to the COVID-19 outbreak.


title: Respiratory viral infections and effects of meteorological parameters and air pollution in adults with respiratory symptoms admitted to the emergency room

text: BACKGROUND: Respiratory viral infections (RVIs) are the most common causes of respiratory infections. The prevalence of respiratory viruses in adults is underestimated. Meteorological variations and air pollution are likely to play a role in these infections. OBJECTIVES: The objectives of this study were to determine the number of emergency visits for influenza-like illness (ILI) and severe acute respiratory infection (SARI) and to evaluate the association between ILI/SARI, RVI prevalence, and meteorological factors/air pollution, in the city of Porto Alegre, Brazil, from November 2008 to October 2010. METHODS: Eleven thousand nine hundred and fifty-three hospitalizations (adults and children) for respiratory symptoms were correlated with meteorological parameters and air pollutants. In a subset of adults, nasopharyngeal aspirates were collected and analyzed through IFI test. The data were analyzed using time-series analysis. RESULTS: Influenza-like illness and SARI were diagnosed in 3698 (30·9%) and 2063 (17·7%) patients, respectively. Thirty-seven (9·0%) samples were positive by IFI and 93 of 410 (22·7%) were IFI and/or PCR positive. In a multivariate logistic regression model, IFI positivity was statistically associated with absolute humidity, use of air conditioning, and presence of mold in home. Sunshine duration was significantly associated with the frequency of ILI cases. For SARI cases, the variables mean temperature, sunshine duration, relative humidity, and mean concentration of pollutants were singnificant. CONCLUSIONS: At least 22% of infections in adult patients admitted to ER with respiratory complaints were caused by RVI. The correlations among meteorological variables, air pollution, ILI/SARI cases, and respiratory viruses demonstrated the relevance of climate factors as significant underlying contributors to the prevalence of RVI.


docid: rqeultbq

title: A short review on antibody therapy for COVID-19

text: Abstract The beginning of the novel SARS-CoV-2 human coronavirus in Wuhan, China, has triggered a worldwide respiratory disease outbreak (COVID-19). By April 07, 2020, SARS-CoV-2 has affected more than 1.36 million people worldwide and caused more than 75,900 deaths. To date, the anti-malaria drug hydroxychloroquine found to be a treatment option for SARS-CoV-2. In addition to supportive treatment, such as oxygen supply in moderate cases and extracorporeal membrane oxygenation in critically ill patients, unique medications for this condition are also under investigation. Here we reviewed the antibody therapy might be an immediate strategy for emergency prophylaxis and SARS-CoV-2 therapy.


title: Towards reduction in bias in epidemic curves due to outcome misclassification through Bayesian analysis of time-series of laboratory test results: Case study of COVID-19 in Alberta, Canada and Philadelphia, USA

text: The aim of our work was to better understand misclassification errors in identification of true cases of COVID-19 and to study the impact of these errors in epidemic curves. We examined publically available time-series data of laboratory tests for SARS-CoV-2 viral infection, the causal agent for COVID-19, to try to explore, using a Bayesian approach, about the sensitivity and specificity of the PCR-based diagnostic test. Data originated from Alberta, Canada (available on 3/28/2020) and city of Philadelphia, USA (available on 3/31/2020). Our analysis revealed that the data were compatible with near-perfect specificity but it was challenging to gain information about sensitivity (prior and posterior largely overlapped). We applied these insights to uncertainty/bias analysis of epidemic curves into jurisdictions under the assumptions of both improving and degrading sensitivity. If the sensitivity improved from 60 to 95%, the observed and adjusted epidemic curves likely fall within the 95% confidence intervals of the observed counts. However, bias in the shape and peak of the epidemic curves can be pronounced, if sensitivity either degrades or remains poor in the 60–70% range. In the extreme scenario, hundreds of undiagnosed cases, even among tested, are possible, potentially leading to further unchecked contagion should these cases not self-isolate. The best way to better understand bias in the epidemic curves of COVID-19 due to errors in testing is to empirically evaluate misclassification of diagnosis in clinical settings and apply this knowledge to adjustment of epidemic curves, a task for which the Bayesian method we presented is well-suited.


docid: drtviivx

title: Critical care capacity in Canada: results of a national cross-sectional study

text: INTRODUCTION: Intensive Care Units (ICUs) provide life-supporting treatment; however, resources are limited, so demand may exceed supply in the event of pandemics, environmental disasters, or in the context of an aging population. We hypothesized that comprehensive national data on ICU resources would permit a better understanding of regional differences in system capacity. METHODS: After the 2009–2010 Influenza A (H1N1) pandemic, the Canadian Critical Care Trials Group surveyed all acute care hospitals in Canada to assess ICU capacity. Using a structured survey tool administered to physicians, respiratory therapists and nurses, we determined the number of ICU beds, ventilators, and the ability to provide specialized support for respiratory failure. RESULTS: We identified 286 hospitals with 3170 ICU beds and 4982 mechanical ventilators for critically ill patients. Twenty-two hospitals had an ICU that routinely cared for children; 15 had dedicated pediatric ICUs. Per 100,000 population, there was substantial variability in provincial capacity, with a mean of 0.9 hospitals with ICUs (provincial range 0.4-2.8), 10 ICU beds capable of providing mechanical ventilation (provincial range 6–19), and 15 invasive mechanical ventilators (provincial range 10–24). There was only moderate correlation between ventilation capacity and population size (coefficient of determination (R(2)) = 0.771). CONCLUSION: ICU resources vary widely across Canadian provinces, and during times of increased demand, may result in geographic differences in the ability to care for critically ill patients. These results highlight the need to evolve inter-jurisdictional resource sharing during periods of substantial increase in demand, and provide background data for the development of appropriate critical care capacity benchmarks. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-015-0852-6) contains supplementary material, which is available to authorized users.


Breaking Social Isolation Amidst COVID‐19: A Viewpoint on Improving Access to Technology in Long‐Term Care Facilities


title: COVID‐19 and Union Prevention

text: One month ago, few people could have foreseen the scope and impact of the COVID‐19 pandemic. At the time of this writing for the current issue of Management Report, the United States has the most confirmed cases of COVID‐19 in the world, the death toll is climbing, and experts say the situation will get worse before it gets better. Commerce in large areas of the country, including California and the Northeast, has largely shut down. The U.S. secretary of the treasury recently suggested that the U.S. unemployment rate could reach as high as 20 percent. Some economists have said it could go as high as during the economic devastation of the Great Depression, when the unemployment rate peaked at nearly 25 percent in 1933. Other economists have said it may reach 30 percent. It has been predicted that 37 million jobs may be the subject of temporary layoffs during this crisis, and 10 million may be lost permanently.


title: Using population-wide administrative and laboratory data to estimate type- and subtype-specific influenza vaccine effectiveness: a surveillance protocol

text: INTRODUCTION: The appropriateness of using routinely collected laboratory data combined with administrative data for estimating influenza vaccine effectiveness (VE) is still being explored. This paper outlines a protocol to estimate influenza VE using linked laboratory and administrative data which could act as a companion to estimates derived from other methods. METHODS AND ANALYSIS: We will use the test-negative design to estimate VE for each influenza type/subtype and season. Province-wide individual-level records of positive and negative influenza tests at the Provincial Laboratory for Public Health in Alberta will be linked, by unique personal health numbers, to administrative databases and vaccination records held at the Ministry of Health in Alberta to determine covariates and influenza vaccination status, respectively. Covariates of interests include age, sex, immunocompromising chronic conditions and healthcare setting. Cases will be defined based on an individual’s first positive influenza test during the season, and potential controls will be defined based on an individual’s first negative influenza test during the season. One control for each case will be randomly selected based on the week the specimen was collected. We will estimate VE using multivariable logistic regression. ETHICS AND DISSEMINATION: Ethics approval was obtained from the University of Alberta’s Health Research Ethics Board—Health Panel under study ID Pro00075997. Results will be disseminated by public health officials in Alberta.


title: Passengers' destinations from China: low risk of Novel Coronavirus (2019-nCoV) transmission into Africa and South America

text: Novel Coronavirus (2019-nCoV [SARS-COV-2]) was detected in humans during the last week of December 2019 at Wuhan city in China, and caused 24 554 cases in 27 countries and territories as of 5 February 2020. The objective of this study was to estimate the risk of transmission of 2019-nCoV through human passenger air flight from four major cities of China (Wuhan, Beijing, Shanghai and Guangzhou) to the passengers' destination countries. We extracted the weekly simulated passengers' end destination data for the period of 1–31 January 2020 from FLIRT, an online air travel dataset that uses information from 800 airlines to show the direct flight and passengers' end destination. We estimated a risk index of 2019-nCoV transmission based on the number of travellers to destination countries, weighted by the number of confirmed cases of the departed city reported by the World Health Organization (WHO). We ranked each country based on the risk index in four quantiles (4(th) quantile being the highest risk and 1(st) quantile being the lowest risk). During the period, 388 287 passengers were destined for 1297 airports in 168 countries or territories across the world. The risk index of 2019-nCoV among the countries had a very high correlation with the WHO-reported confirmed cases (0.97). According to our risk score classification, of the countries that reported at least one Coronavirus-infected pneumonia (COVID-19) case as of 5 February 2020, 24 countries were in the 4(th) quantile of the risk index, two in the 3(rd) quantile, one in the 2(nd) quantile and none in the 1(st) quantile. Outside China, countries with a higher risk of 2019-nCoV transmission are Thailand, Cambodia, Malaysia, Canada and the USA, all of which reported at least one case. In pan-Europe, UK, France, Russia, Germany and Italy; in North America, USA and Canada; in Oceania, Australia had high risk, all of them reported at least one case. In Africa and South America, the risk of transmission is very low with Ethiopia, South Africa, Egypt, Mauritius and Brazil showing a similar risk of transmission compared to the risk of any of the countries where at least one case is detected. The risk of transmission on 31 January 2020 was very high in neighbouring Asian countries, followed by Europe (UK, France, Russia and Germany), Oceania (Australia) and North America (USA and Canada). Increased public health response including early case recognition, isolation of identified case, contract tracing and targeted airport screening, public awareness and vigilance of health workers will help mitigate the force of further spread to naïve countries.


title: New technologies, potential unemployment and ‘nescience economy’ during and after the 2020 economic crisis

text: The coronavirus pandemic and the economic crisis in 2020 are accelerating digital transformation. During and after the crisis, there are opportunities and needs for remote work facilities, online services, delivery drones, etc. We discuss how unmanned technologies can cause a long‐term employment decrease, and why compensation mechanisms may not work. Using the internationally comparable Frey–Osborne methodology, we estimated that less than a third of employees in Russia work in professions with a high automation probability. Some of these professions can suffer the most during quarantine measures; employment in traditional services can be significantly reduced. By 2030, about half of the jobs in the world and a little less in Russia will need to adapt during the fourth industrial revolution because they are engaged in routine, potentially automated activities. In the regions, specializing in manufacturing, this value is higher; the lowest risk is in the largest agglomerations with a high share of digital economy, greater and diverse labour markets. Accelerating technological change can lead to a long‐term mismatch between the exponential increase in automation rate and compensating effects of retraining, new jobs creation and other labour market adaptation mechanisms. Some people will not be ready for a life‐long learning and competition with robots, and accordingly there is a possibility of their technological exclusion. The term “nescience economy” and corresponding assessment method were proposed. Using an econometric model, we identified factors that reduce these risks: human capital concentration, favourable business climate, high quality of life and ICT development. Based on these factors, some recommendations for authorities were proposed in the conclusion.


title: Diagnostic delays in 537 symptomatic cases of Middle East respiratory syndrome coronavirus infection in Saudi Arabia

text: Abstract Background Although the literature indicates that patient delays in seeking medical support for Middle East respiratory syndrome coronavirus (MERS-CoV) infections are associated with poor clinical outcomes, delays in the diagnosis itself remain poorly understood in these patients. This study aimed to determine the median time interval from symptom onset to a confirmed diagnosis and to identify the potential predictors of this interval in Saudi Arabian MERS patients. Methods This was a retrospective study of patients with confirmed MERS who were publicly reported by the World Health Organization (WHO). Results Five hundred and thirty-seven symptomatic cases of MERS-CoV infection were included. The median time interval between symptom onset and confirmation of the MERS diagnosis was 4 days (interquartile range 2–7 days), ranging from 0 to 36 days. According to the negative binomial model, the unadjusted rate ratio (RR) of delays in the diagnosis was significantly higher in older patients (>65 years) (RR 1.42), non-healthcare workers (RR 1.74), patients with severe illness (RR 1.22), those with an unknown source of infection (RR 1.84), and those who had been in close contact with camels (RR 1.74). After accounting for confounders, the adjusted rate ratio (aRR) of delays in the diagnosis was independently associated with unknown source of infection (aRR 1.68) and close contact with camels (aRR 1.58). Conclusions The time interval from symptom onset to diagnosis was greater in older patients, non-healthcare workers, patients with severe illness, patients with an unknown source of infection, and patients who had been in close contact with camels. The findings warrant educational interventions to raise general public awareness of the importance of early symptom notification.


Contribution of certified registered nurse anesthetists to the management of the COVID-19 pandemic health crisis


title: dsRNA binding characterization of full length recombinant wild type and mutants Zaire ebolavirus VP35

text: Abstract The Ebola viruses (EBOVs) VP35 protein is a multifunctional major virulence factor involved in EBOVs replication and evasion of the host immune system. EBOV VP35 is an essential component of the viral RNA polymerase, it is a key participant of the nucleocapsid assembly and it inhibits the innate immune response by antagonizing RIG-I like receptors through its dsRNA binding function and, hence, by suppressing the host type I interferon (IFN) production. Insights into the VP35 dsRNA recognition have been recently revealed by structural and functional analysis performed on its C-terminus protein. We report the biochemical characterization of the Zaire ebolavirus (ZEBOV) full-length recombinant VP35 (rVP35)–dsRNA binding function. We established a novel in vitro magnetic dsRNA binding pull down assay, determined the rVP35 optimal dsRNA binding parameters, measured the rVP35 equilibrium dissociation constant for heterologous in vitro transcribed dsRNA of different length and short synthetic dsRNA of 8bp, and validated the assay for compound screening by assessing the inhibitory ability of auryntricarboxylic acid (IC50 value of 50μg/mL). Furthermore, we compared the dsRNA binding properties of full length wt rVP35 with those of R305A, K309A and R312A rVP35 mutants, which were previously reported to be defective in dsRNA binding-mediated IFN inhibition, showing that the latter have measurably increased K d values for dsRNA binding and modified migration patterns in mobility shift assays with respect to wt rVP35. Overall, these results provide the first characterization of the full-length wt and mutants VP35–dsRNA binding functions.


title: Identification of Potential Vaccine Candidates Against Streptococcus pneumoniae by Reverse Vaccinology Approach

text: In the past few decades, genome-based approaches have contributed significantly to vaccine development. Our aim was to identify the most conserved and immunogenic antigens of Streptococcus pneumoniae, which can be potential vaccine candidates in the future. BLASTn was done to identify the most conserved antigens. PSORTb 3.0.2 was run to predict the subcellular localization of the proteins. B cell epitope prediction was done for the immunogenicity testing. Finally, BLASTp was done for verifying the extent of similarity to human proteome to exclude the possibility of autoimmunity. Proteins failing to comply with the set parameters were filtered at each step. Based on the above criteria, out of the initial 22 pneumococcal proteins selected for screening, pavB and pullulanase were the most promising candidate proteins.


title: Adenovirus receptors and their implications in gene delivery

text: Adenoviruses (Ads) have gained popularity as gene delivery vectors for therapeutic and prophylactic applications. Ad entry into host cells involves specific interactions between cell surface receptors and viral capsid proteins. Several cell surface molecules have been identified as receptors for Ad attachment and entry. Tissue tropism of Ad vectors is greatly influenced by their receptor usage. A variety of strategies have been investigated to modify Ad vector tropism by manipulating the receptor-interacting moieties. Many such strategies are aimed at targeting and/or detargeting of Ad vectors. In this review, we discuss the various cell surface molecules that are implicated as receptors for virus attachment and internalization. Special emphasis is given to Ad types that are utilized as gene delivery vectors. Various strategies to modify Ad tropism using the knowledge of Ad receptors are also discussed.


docid: eewdmyou

title: Regulation of Ribosomal Proteins on Viral Infection

text: Ribosomal proteins (RPs), in conjunction with rRNA, are major components of ribosomes involved in the cellular process of protein biosynthesis, known as “translation”. The viruses, as the small infectious pathogens with limited genomes, must recruit a variety of host factors to survive and propagate, including RPs. At present, more and more information is available on the functional relationship between RPs and virus infection. This review focuses on advancements in my own understanding of critical roles of RPs in the life cycle of viruses. Various RPs interact with viral mRNA and proteins to participate in viral protein biosynthesis and regulate the replication and infection of virus in host cells. Most interactions are essential for viral translation and replication, which promote viral infection and accumulation, whereas the minority represents the defense signaling of host cells by activating immune pathway against virus. RPs provide a new platform for antiviral therapy development, however, at present, antiviral therapeutics with RPs involving in virus infection as targets is limited, and exploring antiviral strategy based on RPs will be the guides for further study.


title: Suspected COVID-19 case definition: a narrative review of the most frequent signs and symptoms among confirmed cases Definição de caso suspeito da COVID-19: uma revisão narrativa dos sinais e sintomas mais frequentes entre os casos confirmados/ Defin

text: Abstract Objective to describe the most frequent signs and symptoms of infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Methods this is a narrative literature review carried out in April 2020;the search was performed on electronic databases and complemented with a manual review of the references of the selected papers and Brazilian Ministry of Health publications Results the spectrum of clinical disease was wide;fever, coughing and dyspnea were the most frequent signs/symptoms, however, they may not be present, thus hindering case definition;gastrointestinal symptoms and loss of taste or smell have been reported among mild cases;dyspnea was frequent among severe and fatal cases Conclusion considering the scarcity of diagnostic tests and the diversity of symptoms, health services should use a sensitive case definition, in order to adopt appropriate surveillance, prevention and treatment actions


title: Dynamics of Bacterial Colonization With Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis During Symptomatic and Asymptomatic Viral Upper Respiratory Tract Infection

text: BACKGROUND: Virus is detected in about 80% of upper respiratory tract infections (URTIs) in children and is also detectable in the nasopharynx of 30% of asymptomatic children. The effect of asymptomatic viral infection on the dynamics of bacterial density and colonization of the nasopharynx has not been reported. The current study was performed to assess the presence and density of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the nasopharynx of 4–7-year-old children during URTI and when well. METHODS: Nasal samples were obtained during 4 surveillance periods when children were asymptomatic and whenever they had symptoms of URTI. Respiratory viruses and bacterial pathogens were identified and quantified using polymerase chain reaction. RESULTS: The proportion of children colonized with all 3 bacteria was higher during visits for acute URTI than during asymptomatic surveillance visits. Mean bacterial densities were significantly higher at all visits for all 3 pathogens when a virus was detected. The differences between the means were 1.0, 0.4, and 0.7 log(10) colony-forming unit equivalents per milliliter for S. pneumoniae, H. influenzae, and M. catarrhalis, respectively, compared with visits in which virus was not detected. The percentage of children colonized and density were also higher at asymptomatic visits in which virus was detected than at visits in which virus was not detected. CONCLUSION: The density and frequency of colonization with S. pneumoniae, H. influenzae, and M. catarrhalis in nasal wash samples increase during periods of both symptomatic and asymptomatic viral infection. Increases in bacterial colonization observed during asymptomatic viral infection were nearly the same magnitude as when children were symptomatic.


title: Syndromic surveillance using regional emergency medicine internet()()()()()

text: STUDY OBJECTIVE: We demonstrate the feasibility and utility of emergency department (ED) syndromic surveillance using a regional emergency medicine Internet application to minimize impact on ED and public health staffing. METHODS: Regional (multi-ED) surveillance was established for 2 periods, one characterized by a high-profile national sports event and the other during an international disease outbreak. Counts of patient visits meeting syndrome criteria and total patient visits were reported daily on the secure regional emergency medicine Internet site and downloaded by public health staff. Trends were analyzed and displayed on the secure Web site. ED participants were surveyed about the acceptability and time cost of the project. RESULTS: In the first (“All Star Game”) project, 8 departments reported daily counts for 4 weeks, covering more than 26,000 patient visits. In the second (“severe acute respiratory syndrome” [SARS]) project, an average of 11 departments in the same region reported daily data on febrile respiratory illnesses, travel, and contacts for 10 weeks. Experience with the first project allowed for rapid implementation of the second project during a 3-day period. In both instances, the surveillance efforts were undertaken without the need for extraordinary ED or public health staffing requirements. CONCLUSION: A regional emergency medicine Internet approach permitted rapid implementation of multisite syndromic surveillance without additional staff. Some problems were identified with the first project, related to clinician checklist completion and manual data tabulation and entry. The SARS project addressed these by simplifying data collection and restricting it to triage.


title: Impact of COVID-19 on thyroid cancer surgery and adjunct therapy

text: COVID-19 has profoundly modified the way healthcare is delivered. Jordan imposed lockdown and restrictive policies between March 17 and May 20, 2020. We aimed to assess the impact of such measures on thyroid cancer treatment plans. In the specified period, 12 patients were scheduled for surgery. Since papillary carcinoma was the preoperative diagnosis in all cases, radioactive iodine ablation (RIA) therapy was also planned 3–4 weeks following surgery after withdrawing thyroxine and achieving a thyroid stimulating hormone (TSH) level > 30 mU/L. Thyroxine withdrawal is the routine method applied for RIA in Jordan as it is less costly compared to the rapid method of exogenous stimulation using recombinant TSH. All surgical procedures were performed without delay since all patients were asymptomatic per flu-like illness and came from a region of low COVID-19 prevalence. These included total thyroidectomy (n = 11), bilateral therapeutic central compartment neck dissection (n = 7), lateral compartment neck dissection (n = 5). However, the RIA treatment plan was altered considerably according to the period in which they were operated. 6 out of the 7 patients operated in March changed to the stimulated method of RIA at a considerable additional extra cost. The seventh patient and the April patient opt to delay RIA until after lockdown. The remaining cases (operated in May) followed the usual withdrawal method as restrictions were due to an end. The restrictive measures applied during COVID-19 did not affect the safe and timely delivery of surgical care. However, it added a financial and psychological burden to the entire cancer management plan.


title: The challenge of PRRS immunology

text: Abstract Porcine reproductive and respiratory syndrome (PRRS) is one of the most challenging subjects of research in veterinary viral immunology, and the immune response against PRRS virus (PRRSV) still is poorly understood. Infected pigs develop a strong and rapid humoral response but these initial antibodies do not confer protection and can even be harmful by mediating an antibody-dependent enhancement of disease. In contrast, development of neutralising antibodies (NAs) is delayed and generation of cell-mediated immune responses, such as PRRSV-specific interferon (IFN)-γ secreting cells, is initially erratic. In spite of this, induction of strong and rapid NAs and IFN-γ responses seem to be required for effective vaccination. PRRSV strongly modulates the host’s immune responses. The virus inhibits key cytokines, such as IFN-α, and may induce regulatory cytokines, such as interleukin (IL)-10. Development of NAs seems to be impaired by the existence of a decoy epitope close to the main neutralisation epitope in glycoprotein 5. This ability to modulate the host immune response probably varies among strains or isolates. The genetic diversity of the virus is very high and it has been shown that this diversity can have serious implications for the development of vaccines, since the immunity induced by one strain may be only partial against a different strain, even within the same genotype. With this panorama, the development of newer and universally efficacious PRRSV vaccines is challenging, but the present state of knowledge allows optimism if collaborative efforts are undertaken in the scientific community.


title: Epidemiology and Clinical Features of Human Coronaviruses in the Pediatric Population

text: BACKGROUND: The epidemiology and clinical features of human coronaviruses (HCoVs) in children are not fully characterized. METHODS: A retrospective study of children with HCoV detected by reverse-transcriptase polymerase chain reaction (RT-PCR) was performed for a community cohort and a children’s hospital in the same community from January 2013 to December 2014. The RT-PCR assay detected HCoV 229E, HKU1, NL63, and OC43 in nasal swabs from symptomatic children ≤18 years. Factors associated with increased severity of illness in hospitalized children were assessed by multivariable logistic regression. RESULTS: Human coronavirus was detected in 261 children, 49 and 212 from the community and hospital, respectively. The distribution of HCoV types and seasonal trends were similar in the community and hospital. Community cases were older than hospitalized cases (median age, 4.4 versus 1.7 years, respectively; P < .01), and a minority of community cases (26.5%) sought medical attention. Among the hospitalized children with HCoV detected, 39 (18.4%) received respiratory support and 24 (11.3%) were admitted to the pediatric intensive care unit (PICU). Age <2 years (odds ratio [OR] = 5.0; 95% confidence interval [CI], 1.9–13.1) and cardiovascular (OR = 3.9; 95% CI, 1.6–9.5), genetic/congenital (OR = 2.8; 95% CI, 1.1–7.0), and respiratory chronic complex conditions ([CCCs] OR = 4.5; 95% CI, 1.7–12.0) were associated with receiving respiratory support. Genetic/congenital (OR = 2.8; 95% CI, 1.1–7.4) CCCs were associated with PICU admission. Severity of illness was similar among hospitalized children with different HCoV types. CONCLUSIONS: Children in the community with HCoV detected generally had mild illness as demonstrated by few medically attended cases. In hospitalized children, young age and CCCs, but not HCoV type, were associated with increased severity of illness.


title: Portable sequencing, genomic data, and scale in global emerging infectious disease surveillance

text: Emerging infectious diseases (EIDs) occur when pathogens unpredictably spread into new contexts. EID surveillance systems seek to rapidly identify EID outbreaks to contain spread and improve public health outcomes. Sequencing data has historically not been integrated into real‐time responses, but portable DNA sequencing technology has prompted optimism among epidemiologists. Specifically, attention has focused on the goal of a “sequencing singularity”: the integration of portable sequencers in a worldwide event‐based surveillance network with other digital data (Gardy & Loman, Nature Reviews Genetics, 19, 2018, p. 9). The sequencing singularity vision is a powerful socio‐technical imaginary, shaping the discourse around the future of portable sequencing. Ethical and practical issues are bound by the vision in two ways: they are framed only as obstacles, and they are formulated only at the scales made visible by its implicit geography. This geography privileges two extremes of scale – the genomic and the global – and leaves intermediate scales comparatively unmapped. We explore how widespread portable sequencing could challenge this geography. Portable sequencers put the ability to produce genomic data in the hands of the individual. The explicit assertion of rights over data may therefore become a matter disputed more at an interpersonal scale than an international one. Portable sequencers also promise ubiquitous, indiscriminate sequencing of the total metagenomic content of samples, raising the question of what (or who) is under surveillance and inviting consideration of the human microbiome and more‐than‐human geographies. We call into question a conception of a globally integrated stream of sequencing data as composed mostly of “noise,” within which signals of pathogen “emergence” are “hidden,” considering it instead from the perspective of recent work into more‐than‐human geographies. Our work highlights a practical need for researchers to consider both the alternative possibilities they foreclose as well as the exciting opportunities they move towards when they deploy their visions of the future.


title: S1 Subunit of Spike Protein from a Current Highly Virulent Porcine Epidemic Diarrhea Virus Is an Important Determinant of Virulence in Piglets

text: Base on the sequence of S genes, which encode spike proteins, we previously identified three different types (North American, S INDEL, and S large-DEL types) of porcine epidemic diarrhea virus (PEDV) that have re-emerged in Japan since 2013. Based on experimental infections with the North American and S large-DEL types, we also hypothesized that PEDV virulence may be linked to the S1 subunit of the S protein. To test this hypothesis, we have now assayed in gnotobiotic piglets various recombinant PEDVs generated by reverse genetics. Piglets inoculated with CV777 maintained in National Institute of Animal Health, along with piglets infected with a recombinant form of the same virus, developed subclinical to mild diarrhea. In contrast, severe watery diarrhea, dehydration, weight loss, astasia, and high mortality were observed in piglets inoculated with recombinant strains in which the S gene was partially or fully replaced with corresponding sequences from the highly virulent Japanese PEDV isolate OKN-1/JPN/2013. Indeed, symptoms resembled those in piglets inoculated with the OKN-1/JPN/2013, and were especially pronounced in younger piglets. Collectively, the data demonstrate that the S1 subunit of the S protein is an important determinant of PEDV virulence, and advance development of new vaccine candidate.


title: Identification of a Nidovirales Orf1a N7-guanine cap Methyltransferase signature-sequence as a genetic marker of large genome Tobaniviridae

text: Members of the Nidovirales order have (+)RNA genomes amongst the largest in size in the RNA virus world. Expression of their genes is promoted through reading of genomic RNA and mRNA transcripts by the ribosome of the infected cell. The 5’-end of these RNAs is supposedly protected by an RNA-cap structure (m7GpppNm) whose most synthesis steps remain elusive. In Eukaryotes, the RNA-cap structure is methylated by RNA methyltransferases (MTases) at the RNA-cap N7-guanine position as well as the 2’-O methyl position of the first transcribed nucleotide. In Coronaviridae, two separate enzymes (nsp14 and nsp16) perform the N7-guanine and the 2’-OH methylation, respectively. One salient feature of the Nidovirales N7-guanine MTase nsp14 is that it is the only example of non-Rossman fold viral MTase known so far. Conversely, all other Nidovirales nsp16-like MTases have a canonical Rossman fold. Many Nidovirales members lack either any RNA MTase signature sequence (e.g., Arteriviridae), or lack a N7-guanine MTase signature sequence (e.g., Tobaniviridae, Euroniviridae, Roniviridae, Medioniviridae). Both nsp14-and nsp16-like enzyme genes are usually located in Orf1b encoding for the replication machinery. Here, we report the discovery of a putative Rossman fold RNA MTase in the Orf1a of ten Tobaniviridae members. Multiple sequence alignments and structural analyses identify this novel gene as a typical RNA-cap N7-guanine MTase with substrate specificity and active-site organization similar to the canonical eukaryotic RNA-cap N7-guanine MTase.


docid: wdnnjlcw

title: Postdigital Research in the Time of Covid-19

text: The First 80 Days of Covid-19 The first case of the coronavirus disease, Covid-19, was officially reported from Wuhan, China, on 31 December 2019 (World Health Organization 2020a) The coronavirus disease had initially been compared with an ordinary flu, and Dr Li Wenliang, who raised the alarm in the early days of the outbreak, was investigated by the Chinese police and the Public Security Bureau for ‘spreading rumours’ Yet it soon became obvious that Covid-19 is far more dangerous than the flu, and Dr Li Wenliang, aged 33, died of the infection on 7 February 2020 (Hegarty 2020) In spite of their harsh initial reactions to Dr Li Wenliang’s alleged whistleblowing, Chinese authorities soon exhibited remarkable determination in containing the virus By late January, they quarantined the city of Wuhan (11 million inhabitants) and several other areas affecting over 60 million of people ‘Since February 18, China has reported the number of recovered cases is vastly outpacing the number of new confirmed cases each day ’ (Roper 2020) In the meantime, the coronavirus has crossed the borders of China, and Western countries have been much slower in their response On 11 March, the World Health Organization ‘declared COVID-19 a pandemic, pointing to the over 118,000 cases of the coronavirus illness in over 110 countries and territories around the world and the sustained risk of further global spread’ (Ducharme 2020) and on 13 March, ‘[i] nternational health officials said Friday that Europe has become the epicenter of the coronavirus pandemic, as the continent is now producing more new cases each day than China did at the height of its crisis’ (Coote and Jacobson 2020) In popular media, the Covid-19 pandemic has started an infodemic of unprecedented scale;fake news and bullshit flourish alongside credible information from sources such as the World Health Organization In the context of research, the Covid-19 pandemic has initiated historically unprecedented levels of collaboration and openness, prompting some authors to suggest that ‘[w] hen the story of the coronavirus (2019-nCOV) is finally written, it might well become a template for the utopian dream of open science — where research data is shared freely, unrestrained by competition, paywalls and patents’ (Crowe 2020) Worldwide closures of schools and universities have pushed millions of students and teachers online, bringing decades of experience in the field under the public eye (Bates 2020) Commentators compare Chinese and Western responses to the crisis, often under bombastic titles such as ‘Coronavirus and the Clash of Civilizations’ (Maçães 2020) Political scientists discuss whether the pandemic is an argument for total dismissal of capitalism or just a passing aberration in its functioning (Roberts 2020) Economists advise us to prepare the new recession (Elliott 2020) Sociologists see worldwide border closures as an anti-globalization experiment (Peters et al 2020), and philosophers go back to questions pertaining to human nature Worldwide governments are responding in radically different ways—the government of Montenegro has closed down the whole country before it registered the first patient within its borders (World Health Organization 2020b), while the UK has opted for a laissez faire approach which is hoped to result in herd immunity (Dunn and Kahn 2020) From official news to social networks, everyone and anyone has something to contribute to these debates, creating an infodemic which will be analysed long after Covid-19 is gone As I write these words on 16 March 2020 from self-isolation in my flat in Zagreb, Croatia, the future of the pandemic is unclear We have no idea what percentage of the global population will be affected by the virus, whether the virus will mutate, how many people the virus might kill, and what might happen with our politics and economy after the pandemic is gone At this point, we need to develop immediate measures to protect ourselves individually and collectively—weed out reliable information, self-isolate, reduce panic, develop educated guesses and emergency plans However, these urgent measures cannot arrive from thin air, and it is just as important to step back and take a birds-eye, longue durée view at the pandemic While doctors, nurses, politicians, food suppliers, and many other brave people self-sacrifice to support our daily survival, this editorial argues that academics have a unique opportunity, and a moral duty, to immediately start conducting in-depth studies of current events [truncated]


title: Contact Heterogeneity and Phylodynamics: How Contact Networks Shape Parasite Evolutionary Trees

text: The inference of population dynamics from molecular sequence data is becoming an important new method for the surveillance of infectious diseases. Here, we examine how heterogeneity in contact shapes the genealogies of parasitic agents. Using extensive simulations, we find that contact heterogeneity can have a strong effect on how the structure of genealogies reflects epidemiologically relevant quantities such as the proportion of a population that is infected. Comparing the simulations to BEAST reconstructions, we also find that contact heterogeneity can increase the number of sequence isolates required to estimate these quantities over the course of an epidemic. Our results suggest that data about contact-network structure will be required in addition to sequence data for accurate estimation of a parasitic agent's genealogy. We conclude that network models will be important for progress in this area.


title: Immunization with an attenuated severe acute respiratory syndrome coronavirus deleted in E protein protects against lethal respiratory disease

text: Abstract The severe acute respiratory syndrome coronavirus (SARS-CoV) caused substantial morbidity and mortality in 2002–2003. Deletion of the envelope (E) protein modestly diminished virus growth in tissue culture but abrogated virulence in animals. Here, we show that immunization with rSARS-CoV-ΔE or SARS-CoV-Δ[E,6-9b] (deleted in accessory proteins (6, 7a, 7b, 8a, 8b, 9b) in addition to E) nearly completely protected BALB/c mice from fatal respiratory disease caused by mouse-adapted SARS-CoV and partly protected hACE2 Tg mice from lethal disease. hACE2 Tg mice, which express the human SARS-CoV receptor, are extremely susceptible to infection. We also show that rSARS-CoV-ΔE and rSARS-CoV-Δ[E,6-9b] induced anti-virus T cell and antibody responses. Further, the E-deleted viruses were stable after 16 blind passages through tissue culture cells, with only a single mutation in the surface glycoprotein detected. The passaged virus remained avirulent in mice. These results suggest that rSARS-CoV-ΔE is an efficacious vaccine candidate that might be useful if SARS recurred.


title: High prevalence of human bocavirus 1 in infants with lower acute respiratory tract disease in Argentina, 2007 – 2009

text: Abstract Human bocavirus (HBoV) is a parvovirus whose association with respiratory disease is currently under investigation. Objective To determine HBoV prevalence in children with lower acute respiratory infection. Methods We investigated HBoV in 433 nasopharyngeal aspirates collected in 2007–2009 from children 0 to 5 years old hospitalized with bronchiolitis or pneumonia in Córdoba, Argentina. Results The general prevalence of HBoV was 21.5% and the positive cases (HBoV+) were more frequent during winter and spring. The mean age of HBoV+ patients was 6.9 months, with 87.1% of the detections corresponding to infants less than 1 year old (among which the prevalence of HBoV was 26.3% in patients < 3 months of age, 22.1% in 3 to 6 months, 25.3% in 6 to 9 months, and 18.8% in 9 to 12 months). The sequence analysis of the NP1 coding region of 15 isolates showed that all isolates from Cordoba were HBoV1 which exhibited a homology of nearly 100% both among themselves and with the originally discovered virus from 2005. Conclusion Overall, our results indicate that HBoV is a significant pathogen that contributes to acute respiratory infection both on its own and during coinfection with other viruses.


In this together: China-EU relations in the COVID-19 era


Multisystem Inflammatory Syndrome in Children (MIS-C) and Kawasaki Disease: Two Different Illnesses with Overlapping Clinical Features


title: The Endless Challenges of Arboviral Diseases in Brazil

text: In this Editorial, we list and discuss some of the main challenges faced by the population and public health authorities in Brazil concerning arbovirus infections, including the occurrence of concurrent epidemics like the ongoing SARS-CoV-2/COVID-19 pandemic.


title: Characteristics of Peripheral Lymphocyte Subset Alteration in COVID-19 Pneumonia

text: BACKGROUND: In December 2019, novel coronavirus (SARS-CoV-2) pneumonia (COVID-19) was reported in Wuhan and has since rapidly spread throughout China. We aimed to clarify the characteristics and clinical significance of peripheral lymphocyte subset alteration in COVID-19. METHODS: The levels of peripheral lymphocyte subsets were measured by flow cytometry in 60 hospitalized COVID-19 patients before and after treatment, and their association with clinical characteristics and treatment efficacy was analyzed. RESULTS: Total lymphocytes, CD4(+) T cells, CD8(+) T cells, B cells, and natural killer (NK) cells decreased in COVID-19 patients, and severe cases had a lower level than mild cases. The subsets showed a significant association with inflammatory status in COVID-19, especially CD8(+) T cells and CD4(+)/CD8(+) ratio. After treatment, 37 patients (67%) showed clinical response, with an increase in CD8(+) T cells and B cells. No significant change in any subset was detected in nonresponsive cases. In multivariate analysis, posttreatment decrease in CD8(+) T cells and B cells and increase in CD4(+)/CD8(+) ratio were indicated as independent predictors of poor efficacy. CONCLUSIONS: Peripheral lymphocyte subset alteration was associated with clinical characteristics and treatment efficacy of COVID-19. CD8(+) T cells tended to be an independent predictor for COVID-19 severity and treatment efficacy.


title: The potential of house flies to act as a vector of avian influenza subtype H5N1 under experimental conditions

text: The objective of the present study was to determine the potential for house flies (Musca domestica L.) (Diptera: Muscidae) to harbour the avian influenza (AI) H5N1 virus. Laboratory‐reared flies were experimentally fed with a mixture containing the AI virus. Exposed flies were washed with brain–heart infusion broth and followed by 70% alcohol before preparation of whole fly homogenate. The homogenate was inoculated into six 10‐day‐old embryonated chicken eggs (ECEs). Allantoic fluids were collected to determine the virus using the haemagglutination (HA) test, reverse transcription‐polymerase chain reaction (RT‐PCR) or quantitative real‐time RT‐PCR (RRT‐PCR). In the first experiment, ECEs that were inoculated with the 50 AI virus exposed fly homogenates died within 48 h and HA and RT‐PCR were positive for AI virus. In the second experiment, ECEs that were inoculated with only one fly died with positive HA test and RT‐PCR. In the last experiment, a group of exposed flies was collected at 0, 6, 12, 24, 36, 48, 72 and 96 h post‐exposure. Fly homogenates of each time point were tested by virus titration in ECEs and RRT‐PCR. Virus titres declined in relation to exposure time. Furthermore, RRT‐PCR results were positive at any time point. The present study shows that the flies may harbour the AI virus and could act as a mechanical vector of the AI virus.


title: Phagocytic cells contribute to the antibody-mediated elimination of pulmonary-infected SARS coronavirus

text: Abstract While the 2002–2003 outbreak of severe acute respiratory syndrome (SARS) resulted in 774 deaths, patients who were affected with mild pulmonary symptoms successfully recovered. The objective of the present work was to identify, using SARS coronavirus (SARS-CoV) mouse infection models, immune factors responsible for clearing of the virus. The elimination of pulmonary SARS-CoV infection required the activation of B cells by CD4+ T cells. Furthermore, passive immunization (post-infection) with homologous (murine) anti-SARS-CoV antiserum showed greater elimination efficacy against SARS-CoV than that with heterologous (rabbit) antiserum, despite the use of equivalent titers of neutralizing antibodies. This distinction was mediated by mouse phagocytic cells (monocyte-derived infiltrating macrophages and partially alveolar macrophages, but not neutrophils), as demonstrated both by adoptive transfer from donors and by immunological depletion of selected cell types. These results indicate that the cooperation of anti-SARS-CoV antibodies and phagocytic cells plays an important role in the elimination of SARS-CoV.


title: Prevalence of infectious diseases in feral cats in Northern Florida

text: Abstract Objectives of this study were to determine prevalence of infection in feral cats in Northern Florida with a select group of infectious organisms and to determine risk factors for infection. Blood samples or sera from 553 cats were tested with a panel of antibody, antigen or PCR assays. Male cats were at higher risk for FIV, Mycoplasma haemofelis, and M. haemominutum. Infection with either FeLV or FIV was associated with increased risk for coinfection with the other retrovirus, M. haemofelis, or M. haemominutum. Bartonella henselae had the highest prevalence and was the only organism that did not have any associated risk for coinfection with other organisms. Feral cats in this study had similar or lower prevalence rates of infections than those published for pet cats in the United States. Thus, feral cats assessed in this study appear to be of no greater risk to human beings or other cats than pet cats.


title: Residues affecting the chloride regulation and substrate selectivity of the angiotensin‐converting enzymes (ACE and ACE2) identified by site‐directed mutagenesis

text: Angiotensin‐converting enzyme (ACE) and its homologue angiotensin‐converting enzyme 2 (ACE2) are critical counter‐regulatory enzymes of the renin–angiotensin system, and have been implicated in cardiac function, renal disease, diabetes, atherosclerosis and acute lung injury. Both ACE and ACE2 have catalytic activity that is chloride sensitive and is caused by the presence of the CL1 and CL2 chloride‐binding sites in ACE and the CL1 site in ACE2. The chloride regulation of activity is also substrate dependent. Site‐directed mutagenesis was employed to elucidate which of the CL1 and CL2 site residues are responsible for chloride sensitivity. The CL1 site residues Arg186, Trp279 and Arg489 of testicular ACE and the equivalent ACE2 residues Arg169, Trp271 and Lys481 were found to be critical to chloride sensitivity. Arg522 of testicular ACE was also confirmed to be vital to the chloride regulation mediated by the CL2 site. In addition, Arg514 of ACE2 was identified as a residue critical to substrate selectivity, with the R514Q mutant, relative to the wild‐type, possessing a fourfold greater selectivity for the formation of the vasodilator angiotensin‐(1–7) from the vasoconstrictor angiotensin II. The enhancement of angiotensin II cleavage by R514Q ACE2 was a result of a 2.5‐fold increase in V (max) compared with the wild‐type. Inhibition of ACE2 was also found to be chloride sensitive, as for testicular ACE, with residues Arg169 and Arg514 of ACE2 identified as influencing the potency of the ACE2‐specific inhibitor MLN‐4760. Consequently, important insights into the chloride sensitivity, substrate selectivity and inhibition of testicular ACE and ACE2 were elucidated.


title: Prediction of proteinase cleavage sites in polyproteins of coronaviruses and its applications in analyzing SARS‐CoV genomes

text: Recently, we have developed a coronavirus‐specific gene‐finding system, ZCURVE_CoV 1.0. In this paper, the system is further improved by taking the prediction of cleavage sites of viral proteinases in polyproteins into account. The cleavage sites of the 3C‐like proteinase and papain‐like proteinase are highly conserved. Based on the method of traditional positional weight matrix trained by the peptides around cleavage sites, the present method also sufficiently considers the length conservation of non‐structural proteins cleaved by the 3C‐like proteinase and papain‐like proteinase to reduce the false positive prediction rate. The improved system, ZCURVE_CoV 2.0, has been run for each of the 24 completely sequenced coronavirus genomes in GenBank. Consequently, all the non‐structural proteins in the 24 genomes are accurately predicted. Compared with known annotations, the performance of the present method is satisfactory. The software ZCURVE_CoV 2.0 is freely available at http://tubic.tju.edu.cn/sars/.


title: Rates of coinfection with other respiratory pathogens in patients positive for coronavirus disease 2019 (COVID‐19)

text: OBJECTIVES: The purpose of this study was to assess coinfection rates of coronavirus disease 2019 (COVID‐19) with other respiratory infections on presentation. METHODS: This is a retrospective analysis of data from a 2 hospital academic medical centers and 2 urgent care centers during the initial 2 weeks of testing for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) , March 10, 2020 to March 23, 2020. Testing was targeted toward high‐risk patients following US Centers for Disease Control and Prevention guidelines. Demographics include age group and sex. Laboratory test results included SARS‐CoV‐2, rapid influenza A/B, and upper respiratory pathogen nucleic acid detection. Patient demographics and coinfections are presented overall and by test results with descriptive statistics. RESULTS: Complete laboratory results from the first 2 weeks of testing were available for 471 emergency department patients and 117 urgent care center patients who were tested for SARS‐CoV. A total of 51 (8.7%) patients tested positive for COVID‐19 with only 1 of these patients also testing positive for another respiratory infection. One of the patients positive for COVID‐19 also tested positive for influenza A. Among the 537 patients who were screened and tested negative for COVID‐19, there were 33 (6.1%) patients who tested positive in the upper respiratory pathogen nucleic acid detection test. CONCLUSION: In our study investigating coinfections among 51 patients testing positive for COVID‐19, 1 patient also tested positive for influenza A. Although we found limited coinfections in our emergency department and urgent care center patient populations, further research is needed to assess potential coinfection in patients with COVID‐19.


Ferrets further disease research


title: Adaptive multiresolution method for MAP reconstruction in electron tomography

text: Abstract 3D image reconstruction with electron tomography holds problems due to the severely limited range of projection angles and low signal to noise ratio of the acquired projection images. The maximum a posteriori (MAP) reconstruction methods have been successful in compensating for the missing information and suppressing noise with their intrinsic regularization techniques. There are two major problems in MAP reconstruction methods: (1) selection of the regularization parameter that controls the balance between the data fidelity and the prior information, and (2) long computation time. One aim of this study is to provide an adaptive solution to the regularization parameter selection problem without having additional knowledge about the imaging environment and the sample. The other aim is to realize the reconstruction using sequences of resolution levels to shorten the computation time. The reconstructions were analyzed in terms of accuracy and computational efficiency using a simulated biological phantom and publically available experimental datasets of electron tomography. The numerical and visual evaluations of the experiments show that the adaptive multiresolution method can provide more accurate results than the weighted back projection (WBP), simultaneous iterative reconstruction technique (SIRT), and sequential MAP expectation maximization (sMAPEM) method. The method is superior to sMAPEM also in terms of computation time and usability since it can reconstruct 3D images significantly faster without requiring any parameter to be set by the user.


title: Drug Safety Surveillance in China and Other Countries: A Review and Comparison

text: Abstract Objectives Drug safety and postmarketing surveillance have become important public health issues in China. This study reviews the relatively new drug safety surveillance system in China and compares it with the systems in the United States and Europe. Methods An extensive literature review was conducted in the following four areas: 1) the organizational structure of the State Food and Drug Administration (SFDA) in China; 2) the development of an adverse drug reaction (ADR) monitoring system in China; 3) regulatory issues related to drug safety in China; and 4) similarities and differences between drug safety surveillance in China and surveillance in the United States and Europe. Results The SFDA oversees an extensive network of drug safety “watchdogs,” including the China National Center for ADR Monitoring and 32 regional centers throughout China. China's system has faced a number of recent challenges. It has had to respond quickly to the withdrawal of various high-profile drugs like Vioxx (rofecoxib) and Baycol (cerivastatin) from other markets. Together with China's Ministry of Health, the SFDA has faced several unique drug safety events. Three of those events, involving the injectable form of the heartleaf houttuyinia herb (Yu Xing Cao), Armillarisni A injections, and clindamycin glucose infusions (Xinfu), are discussed. The rapid development of drug safety surveillance in China is manifested in extensive organizational structure, development of large databases, and laws and regulations supporting drug safety. The two major laws are the China Drug Administration Law issued in February 2001 and the Regulation for the Administration of ADR Reporting and Monitoring issued in March 2004. The study also discusses and compares recent developments in drug safety surveillance in the United States and the European Union. These developments will most likely have implications for the Chinese system in the near future. Conclusions While postmarketing surveillance guidelines are not yet available in China, we fully expect their eventual issuance after adaptation to the particular culture and clinical practices in China.


title: Site-Specific Photo-Crosslinking Proteomics Reveal Regulation of IFITM3 Trafficking and Turnover by VCP/p97 ATPase

text: Interferon-induced transmembrane protein 3 (IFITM3) is a key interferon effector that broadly prevents infection by diverse viruses. However, the cellular factors that control IFITM3 homeostasis and antiviral activity have not been fully elucidated. Using site-specific photo-crosslinking and quantitative proteomic analysis, here we present the identification and functional characterization of VCP/p97 AAA-ATPase as a primary interaction partner of IFITM3. We show that IFITM3 ubiquitination at lysine 24 is crucial for VCP binding, trafficking, turnover, and engagement with incoming virus particles. Consistently, pharmacological inhibition of VCP/p97 ATPase activity leads to defective IFITM3 lysosomal sorting, turnover, and co-trafficking with virus particles. Our results showcase the utility of site-specific protein photo-crosslinking in mammalian cells and reveal VCP/p97 as a key cellular factor involved in IFITM3 trafficking and homeostasis.


title: Clinical characteristics of 16 patients with COVID-19 infection outside of Wuhan, China: A retrospective, single-center study

text: Background: Since early December 2019, the 2019 novel coronavirus (COVID-19) has emerged in Wuhan and spread rapidly in China. We aimed to describe the clinical characteristics of hospitalized patients with confirmed COVID-19 infection in Shaoxing, and provide an insight into the treatment of COVID-19 across China and elsewhere. Methods: In this retrospective, single-center, study, we enrolled 16 patients with laboratory-confirmed COVID-19 admitted to the Affiliated Hospital of Shaoxing University between February 24 and January 25, 2020. Epidemiological, demographic, clinical, laboratory, radiological feature, and treatment data were all collected. Outcomes were followed up until March 16, 2020. Results: Among the 16 patients with COVID-19 infection, 11 patients (68.8%) had traveled or lived in Wuhan or surrounding areas, and 2 (12.5%) patients had exposure to patients with confirmed COVID-19 infection. The average age of the patients was 44.1 (16.5) years, and there were 10 women (62.5%) and 6 men (37.5%). More than half had chronic diseases [9 (56.3%)]. The most common symptoms at onset of COVID-19 infection were fever [12 (75%)] and cough [8 (50%)]; 11 (68.8%) patients had lymphopenia, and 12 (75%) had elevated C-reactive protein. On admission, abnormalities in computed tomography (CT) or chest X-ray images were revealed among all patients, and 11 (68.8%) of 16 patients had bilateral involvement. All patients were given psychological counseling, 15 (93.8%) patients were administered with antiviral therapy, 8 (50%) received empirical antibiotic treatment, and 5 (31.3%) patients were given systematic corticosteroids. Complications included acute respiratory distress syndrome (ARDS) requiring non-invasive mechanical ventilation [1 (6.3%)], acute respiratory injury [4 (25%)], acute renal injury [1 (6.3%)], septic shock [1 (6.3%)], liver dysfunction [5 (31.3%)], electrolyte disturbance [8 (50.0%)], and hospital-acquired pneumonia [3 (18.8%)]. None of the 16 patients died of COVID-19 pneumonia. Conclusions: Compared with the symptoms of the initial patients with COVID-19 infection in Wuhan, the symptoms of the patients from Shaoxing city were relatively mild. Currently, there is no effective drug treatment or vaccine for COVID-19, and psychological counseling cannot be ignored. Drugs and vaccines against COVID-19 infection need to be developed as soon as possible.


title: Treatment of a Woman With Glycyrrhiza glabra for Acute Sinusitis: A Case Report

text: OBJECTIVE: The purpose of this case report is to describe the treatment of a patient with acute sinusitis using Glycyrrhiza glabra. CLINICAL FEATURES: A 26-year-old woman presented with acute sinusitis of 10-day duration. Her symptoms included facial pressure and soreness around the frontal and maxillary sinuses, a headache, pharyngitis, a fever, rhinorrhea, nasal congestion with postnasal drip, a productive cough, myalgias, and fatigue. INTERVENTION AND OUTCOME: After administration of 12 to 15 drops of a 2 000-mg tincture of G glabra twice a day, improvements were noted. Resolution of her symptoms occurred after 3 days of treatment. CONCLUSION: For the treatment of acute sinusitis, G glabra may be a natural therapeutic remedy.


title: The Role of Medical Student Government in Responding to COVID-19

text: The COVID-19 outbreak has sown clinical and administrative chaos at academic health centers throughout the country. As COVID-19-related burdens on the health care system and medical schools piled up, questions from medical students far outweighed the capacity of medical school administrators to respond in an adequate or timely manner, leaving students feeling confused and without clear guidance. In this Perspective, incoming and outgoing executive leaders of the University of Michigan Medical School Student Council and medical school deans outline the specific ways they were able to bridge the gap between medical students and administrators in a time of crisis. To illustrate the value of student government during uncertain times, the authors identify the most pressing problems faced by students at each phase of the curriculum—preclerkship, clerkship, and postclerkship—and explain how Student Council leadership partnered with administrators to find creative solutions to these problems and provide guidance to learners. They end by reflecting on the role of student government more broadly, identifying 3 guiding principles of student leadership and how these principles enable effective student representation.


Low Cost Homemade System to Disinfect Food Items from SARS-CoV-2


title: Human Neutralizing Monoclonal Antibody Inhibition of Middle East Respiratory Syndrome Coronavirus Replication in the Common Marmoset

text: Middle East respiratory syndrome coronavirus (MERS-CoV) infection in humans is highly lethal, with a fatality rate of 35%. New prophylactic and therapeutic strategies to combat human infections are urgently needed. We isolated a fully human neutralizing antibody, MCA1, from a human survivor. The antibody recognizes the receptor-binding domain of MERS-CoV S glycoprotein and interferes with the interaction between viral S and the human cellular receptor human dipeptidyl peptidase 4 (DPP4). To our knowledge, this study is the first to report a human neutralizing monoclonal antibody that completely inhibits MERS-CoV replication in common marmosets. Monotherapy with MCA1 represents a potential alternative treatment for human infections with MERS-CoV worthy of evaluation in clinical settings.


Interaction Between the Spike Protein of Human Coronavirus NL63 and its Cellular Receptor ACE2


Coronavirus disease-19 and its hematological manifestations


title: Challenges and opportunities in the purification of recombinant tagged proteins

text: Abstract The purification of recombinant proteins by affinity chromatography is one of the most efficient strategies due to the high recovery yields and purity achieved. However, this is dependent on the availability of specific affinity adsorbents for each particular target protein. The diversity of proteins to be purified augments the complexity and number of specific affinity adsorbents needed, and therefore generic platforms for the purification of recombinant proteins are appealing strategies. This justifies why genetically encoded affinity tags became so popular for recombinant protein purification, as these systems only require specific ligands for the capture of the fusion protein through a pre-defined affinity tag tail. There is a wide range of available affinity pairs “tag-ligand” combining biological or structural affinity ligands with the respective binding tags. This review gives a general overview of the well-established “tag-ligand” systems available for fusion protein purification and also explores current unconventional strategies under development.


title: Facial protection in the era of COVID‐19: a narrative review

text: We live in extraordinary times, where COVID‐19 pandemic has brought the whole world to a screeching halt. Tensions and contradictions that surround the pandemic ridden world include the availability, and the lack thereof, various facial protection measures to mitigate the viral spread. Here, we comprehensively explore the different type of facial protection measures, including masks, needed both for the pubic and the health care workers (HCW). We discuss the anatomy, the critical issues of disinfection and reusability of masks, the alternative equipment available for the protection of the facial region from airborne diseases, such as face shields and powered air purifying respirators (PAPR), and the skin‐health impact of prolonged wearing of facial protection by HCW. Clearly, facial protection, either in the form of masks or alternates, appears to have mitigated the pandemic as seen from the minimal COVID‐19 spread in countries where public mask wearing is strictly enforced. On the contrary, the healthcare systems, that appear to have been unprepared for emergencies of this nature, should be appropriately geared to handle the imbalance of supply and demand of personal protective equipment including face masks. These are two crucial lessons we can learn from this tragic experience.


Key highlights from the Canadian Thoracic Society’s Position Statement on the Optimization of Asthma Management during the COVID-19 Pandemic


title: The HIV-1 Envelope Glycoprotein Structure: Nailing down a Moving Target

text: Structure determination of the HIV-1 envelope glycoprotein (Env) presented a number of challenges, but several high-resolution structures have now become available. In 2013, cryo-EM and x-ray structures of soluble, cleaved SOSIP Env trimers from the clade A BG505 strain provided the first glimpses into the Env trimer fold as well as more the variable regions. A recent cryo-EM structure of a native full-length trimer without any stabilizing mutations had the same core structure, but revealed new insights and features. A more comprehensive and higher resolution understanding of the glycan shield has also emerged, enabling a more complete representation of the Env glycoprotein structure. Complexes of Env trimers with broadly neutralizing antibodies have surprisingly illustrated that most of the Env surface can be targeted in natural infection and that the neutralizing epitopes are almost all composed of both peptide and glycan components. These structures have also provided further evidence of the inherent plasticity of Env and how antibodies can exploit this flexibility by perturbing or even stabilizing the trimer to facilitate neutralization. These breakthroughs have stimulated further design and stabilization of Env trimers as well as other platforms to generate trimers that now span multiple subtypes The Env trimers as immunogens have led to the first vaccine-induced neutralizing antibodies for structural and functional analyses.


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title: H1N1 viral proteome peptide microarray predicts individuals at risk for H1N1 infection and segregates infection versus Pandemrix® vaccination

text: A high content peptide microarray containing the entire influenza A virus [A/California/08/2009(H1N1)] proteome and haemagglutinin proteins from 12 other influenza A subtypes, including the haemagglutinin from the [A/South Carolina/1/1918(H1N1)] strain, was used to gauge serum IgG epitope signatures before and after Pandemrix® vaccination or H1N1 infection in a Swedish cohort during the pandemic influenza season 2009. A very narrow pattern of pandemic flu-specific IgG epitope recognition was observed in the serum from individuals who later contracted H1N1 infection. Moreover, the pandemic influenza infection generated IgG reactivity to two adjacent epitopes of the neuraminidase protein. The differential serum IgG recognition was focused on haemagglutinin 1 (H1) and restricted to classical antigenic sites (Cb) in both the vaccinated controls and individuals with flu infections. We further identified a novel epitope VEPGDKITFEATGNL on the Ca antigenic site (251–265) of the pandemic flu haemagglutinin, which was exclusively recognized in serum from individuals with previous vaccinations and never in serum from individuals with H1N1 infection (confirmed by RNA PCR analysis from nasal swabs). This epitope was mapped to the receptor-binding domain of the influenza haemagglutinin and could serve as a correlate of immune protection in the context of pandemic flu. The study shows that unbiased epitope mapping using peptide microarray technology leads to the identification of biologically and clinically relevant target structures. Most significantly an H1N1 infection induced a different footprint of IgG epitope recognition patterns compared with the pandemic H1N1 vaccine.


title: Whole exome sequencing in the differential diagnosis of Diamond-Blackfan anemia: Clinical and molecular study of three patients with novel RPL5 and mosaic RPS19 mutations

text: Abstract Diamond-Blackfan anemia (DBA) is a rare congenital disorder presenting remarkable phenotypic overlap with other inherited bone marrow failure syndromes, making differential diagnosis challenging and its confirmation often reached with great delay. By whole exome sequencing, we unraveled the presence of pathogenic variants affecting genes already known to be involved in DBA pathogenesis (RPL5 and RPS19) in three patients with otherwise uncertain clinical diagnosis, and provided new insights on DBA genotype-phenotype correlations. Remarkably, the RPL5 c.482del frameshift mutation has never been reported before, whereas the RPS19 c.3G>T missense mutation, although previously described in a 2-month-old DBA patient without malformations and refractory to steroid therapy, was detected here in the mosaic state in different bodily tissues for the first time in DBA patients.


title: Evidence of Aujeszky’s disease in wild boar in Serbia

text: BACKGROUND: Aujeszky’s disease is a viral disease of suids caused by Suid Herpesvirus 1. The disease has worldwide distribution with significant economic impact. In Serbia, there is neither an Aujeszky’s disease eradication nor national vaccination programme of domestic pigs. Since clinical symptoms of Aujeszky’s disease are not specific, it is important to establish a link between clinical signs and presence of ADV active infection in wild boars. The aim of this study was to investigate the possibility of active infection within wild boar showing signs of ADV and also to examine relationship between isolates from domestic pigs and wild boar. Having in mind that virus has not been previously isolated from wild boars in Serbia, we report the first isolation of Suid Herpesvirus 1 from this species in Serbia. RESULTS: Tissue and serum samples from 40 wild boars from eastern Serbia were examined for evidence of Aujeszky’s disease (AD). Suid Herpesvirus 1 (SHV1), the cause of AD was isolated on PK15 cell line from three tissue samples, inducing cytopathic effect (CPE) with syncytia forming, and viral genome was detected by polymerase chain reaction (PCR) in eight samples. Genetic analysis of us4, us9 and ul49.5 partial sequences showed high homology between ADV isolates from wild boars and between isolates from wild boars and domestic animals. Neutralizing antibodies were not detected by virus neutralisation test (VNT) in sera from four out of eight PCR positive wild boars suggesting recent infection in those animals. CONCLUSIONS: This is the first demonstration of Aujeszky’s disease virus (ADV) in the wild boar population in Serbia although seroconversion has been detected previously.


SEVERE ASTHMA DURING THE COVID-19 PANDEMIC: CLINICAL OBSERVATIONS


title: Viral infections in patients with hematological malignancies

text: Viral infections remain one of the most frequent complications in patients with hematological malignancies, especially in those receiving an allogeneic stem cell transplantation. Viral infections result from reactivation of latent infection rather than from acquisition of new infection. Infections caused by herpes viruses, including cytomegalovirus and Epstein-Barr virus, respiratory viruses and hepatitis B virus are frequently associated with high morbidity and mortality in the immunocompromised host. Major advances have been made primarily by the availability of rapid diagnostic tests and the introduction of potent antiviral compounds into clinical practice.


title: Impact of porcine epidemic diarrhea on herd and individual Berkshire sow productivity

text: Abstract Porcine epidemic diarrhea (PED) is an emerging disease of pigs in several countries. In the present study, individual sow productivity of Berkshire sows exposed to PED virus at different stages of production was compared. On a commercial farrow-to-finish farm in Kagoshima Prefecture, Japan, the clinical presence of PED was observed in the farrowing barn on January 6, 2014, and all gilts and sows were immunized on January 9, except those in the farrowing barn. The sows were categorized into six groups based on the period in which they were exposed to PED virus: between days 0–30 (G1), 31–60 (G2), 61–90 (G3), or after 91 days of pregnancy (G4), during lactation (L), and after weaning (W). The control group was not exposed to PED during the period of PED outbreak. The study was based on 574 production records. The sows of the G4 and L groups had the fewest piglets weaned (4.8±0.4, and 4.0±0.3 pigs, respectively; P<0.05) and the greatest pre-weaning mortality (33.1±4.8%, and 39.7±4.1%, respectively; P<0.05). The number of piglets weaned and pre-weaning mortality, however, did not differ among the G1, G2, G3, and uninfected groups. The G4 and W groups had slightly lesser farrowing rates than the uninfected group (P<0.05), however, similar subsequent piglet litter performance as the uninfected group. In conclusion, the effect of PED on individual sow productivity differed with the production stage in which sows were exposed to PED virus.


title: Universal primers that amplify RNA from all three flavivirus subgroups

text: BACKGROUND: Species within the Flavivirus genus pose public health problems around the world. Increasing cases of Dengue and Japanese encephalitis virus in Asia, frequent outbreaks of Yellow fever virus in Africa and South America, and the ongoing spread of West Nile virus throughout the Americas, show the geographical burden of flavivirus diseases. Flavivirus infections are often indistinct from and confused with other febrile illnesses. Here we review the specificity of published primers, and describe a new universal primer pair that can detect a wide range of flaviviruses, including viruses from each of the recognised subgroups. RESULTS: Bioinformatic analysis of 257 published full-length Flavivirus genomes revealed conserved regions not previously targeted by primers. Two degenerate primers, Flav100F and Flav200R were designed from these regions and used to generate an 800 base pair cDNA product. The region amplified encoded part of the methyltransferase and most of the RNA-dependent-RNA-polymerase (NS5) coding sequence. One-step RT-PCR testing was successful using standard conditions with RNA from over 60 different flavivirus strains representing about 50 species. The cDNA from each virus isolate was sequenced then used in phylogenetic analyses and database searches to confirm the identity of the template RNA. CONCLUSION: Comprehensive testing has revealed the broad specificity of these primers. We briefly discuss the advantages and uses of these universal primers.


title: Melamine and other food safety and health scares in China: Comparing households with and without young children

text: Abstract The purpose of this study was to determine whether household responses to melamine and other recent food safety and health scares in China in recent years differed between households that did or did not have young children (less than six years of age). A consumer survey was conducted in Hohhot, China in September 2009, one year after the melamine contamination of milk was disclosed to the public. Households with young children who were not being breast-fed reported that they had reduced milk consumption by at least 1/3 in the immediate aftermath of the melamine disclosure and 39% reported that they cut out milk consumption altogether. A significantly higher percentage of households with children reported being concerned with the effects of melamine in milk and two communicable diseases: SARS and H1N1 influenza than were those with no children. A significantly higher percentage of households with no young children were concerned with the effects of Trace Sudan in chicken, Clenbuterol in pork, chicken eggs with red yolks, and excess iodine in milk powder than were those with young children. All households that reduced consumption of fluid milk following news of the melamine contamination reported a much greater concern with most food safety and health scares than did households that did not reduce consumption of fluid milk. Survey data revealed that most consumers had a relatively low level of knowledge of the Food Safety Law that went into effect just over three months before this survey was conducted. Households with children also were significantly more concerned about melamine and two communicable diseases, SARS and H1N1 than were households without children.


title: Case-control study of the epidemiological and clinical features of human adenovirus 55 and human adenovirus 7 infection in children with acute lower respiratory tract infections in Beijing, China, 2008–2013

text: BACKGROUND: In adults, the emerging human adenovirus (HAdV) type 55 (HAdV-55) has been reported to cause more severe cases of adenovirus induced acute lower respiratory tract infections (ALRTIs) compared to other HAdV serotypes (HAdV-3, HAdV-7, HAdV-14). However, there is a dearth of comparative studies in children that address differences in the clinical epidemiological features between HAdV-55 and other HAdV serotypes that can also induce severe infection (such as HAdV-7). METHODS: We conducted a retrospective review of pediatric patients hospitalized at Beijing Children’s Hospital with ALRTI from April 2008 to December 2013 who had adenovirus detected from nasopharyngeal or throat samples by PCR. We further compared pediatric patients infected with HAdV-55 to those infected with HAdV-7 using a case-control methodology by matching each subject with HAdV-55 infection to 4 patients with HAdV-7 infection within 2 months of each HAdV-55 infection. Demographic, clinical, and etiological data were collected and analyzed. RESULTS: Over the five-year period, HAdV was detected in 194 children. Of these, 8 were HAdV-55 positive. Epidemiological results showed that HAdV-55 infection was observed only in 4% of adenovirus infected children whereas HAdV-7 infection proportioned 53%. Most cases of HAdV-55 infection were identified during March and April, whereas HAdV-7 infection occurred throughout the year. Wheezing was significantly less frequent in the HAdV-55 group. No patients infected with HAdV-55 presented with vomiting or had any underlying disease. Coinfections with other respiratory tract pathogens were frequent among children infected with either HAdV-55 or HAdV-7. CONCLUSIONS: HAdV-55 circulated in Beijing during spring and appeared to cause pediatric respiratory infections that were as severe as HAdV-7 infections. Broader surveillance studies are needed.


title: Plant-based solutions for veterinary immunotherapeutics and prophylactics

text: An alarming increase in emergence of antibiotic resistance among pathogens worldwide has become a serious threat to our ability to treat infectious diseases according to the World Health Organization. Extensive use of antibiotics by livestock producers promotes the spread of new resistant strains, some of zoonotic concern, which increases food-borne illness in humans and causes significant economic burden on healthcare systems. Furthermore, consumer preferences for meat/poultry/fish produced without the use of antibiotics shape today’s market demand. So, it is viewed as inevitable by the One Health Initiative that humans need to reduce the use of antibiotics and turn to alternative, improved means to control disease: vaccination and prophylactics. Besides the intense research focused on novel therapeutic molecules, both these strategies rely heavily on the availability of cost-effective, efficient and scalable production platforms which will allow large-volume manufacturing for vaccines, antibodies and other biopharmaceuticals. Within this context, plant-based platforms for production of recombinant therapeutic proteins offer significant advantages over conventional expression systems, including lack of animal pathogens, low production costs, fast turnaround and response times and rapid, nearly-unlimited scalability. Also, because dried leaves and seeds can be stored at room temperature for lengthy periods without loss of recombinant proteins, plant expression systems have the potential to offer lucrative benefits from the development of edible vaccines and prophylactics, as these would not require “cold chain” storage and transportation, and could be administered in mass volumes with minimal processing. Several biotechnology companies currently have developed and adopted plant-based platforms for commercial production of recombinant protein therapeutics. In this manuscript, we outline the challenges in the process of livestock immunization as well as the current plant biotechnology developments aimed to address these challenges.


title: Taking the Longer View of COVID‐19

text: What are the prospects for dealing with COVID‐19 more effectively in the future? This editorial addresses the question from the perspective of long‐term control of coronavirus infection.