title: Parainfluenza virus 5-based vaccine vectors expressing vaccinia virus (VACV) antigens provide long-term protection in mice from lethal intranasal VACV challenge

text: Abstract To test the potential for parainfluenza virus 5 (PIV5)-based vectors to provide protection from vaccinia virus (VACV) infection, PIV5 was engineered to express secreted VACV L1R and B5R proteins, two important antigens for neutralization of intracellular mature (IMV) and extracellular enveloped (EEV) virions, respectively. Protection of mice from lethal intranasal VACV challenge required intranasal immunization with PIV5-L1R/B5R in a prime-boost protocol, and correlated with low VACV-induced pathology in the respiratory tract and anti-VACV neutralizing antibody. Mice immunized with PIV5-L1R/B5R showed some disease symptoms following VACV challenge such as loss of weight and hunching, but these symptoms were delayed and less severe than with unimmunized control mice. While immunization with PIV5 expressing B5R alone conferred at least some protection, the most effective immunization included the PIV5 vector expressing L1R alone or in combination with PIV5-B5R. PIV5-L1R/B5R vectors elicited protection from VACV challenge even when CD8+ cells were depleted, but not in the case of mice that were defective in B cell production. Mice were protected from VACV challenge out to at least 1.5years after immunization with PIV5-L1R/B5R vectors, and showed significant levels of anti-VACV neutralizing antibodies. These results demonstrate the potential for PIV5-based vectors to provide long lasting protection against complex human respiratory pathogens such as VACV, but also highlight the need to understand mechanisms for the generation of strong immune responses against poorly immunogenic viral proteins.


title: What is the role of virus vaccination in patients with asthma?

text: It is estimated that viruses play a role in 30% to 80% of asthma exacerbations. Thus, virus vaccination in patients with asthma could play an important role in preventing asthma exacerbations and other complications. Influenza is the only agent for which a routine vaccine is currently available. This article discusses whether influenza vaccination in patients with asthma, based on the available evidence, is justified. Cost-effectiveness of (influenza) vaccination for patients with asthma is questionable. For the other major viruses involved, the present state of affairs is described. Although progress is being made, a vaccine may be available in the near future only for respiratory syncytial virus (RSV). Meanwhile, clinicians and patients should aim for an optimal treatment with the currently available asthma medication.


title: Generation of Recombinant Coronaviruses Using Vaccinia Virus as the Cloning Vector and Stable Cell Lines Containing Coronaviral Replicon RNAs

text: Coronavirus reverse genetic systems have become valuable tools for studying the molecular biology of coronavirus infections. They have been applied to the generation of recombinant coronaviruses, selectable replicon RNAs, and coronavirus-based vectors for heterologous gene expression. Here we provide a collection of protocols for the generation, cloning, and modification of full-length coronavirus cDNA using vaccinia virus as a cloning vector. Based on cloned coronaviral cDNA, we describe the generation of recombinant coronaviruses and stable cell lines containing coronaviral replicon RNAs. Initially, the vaccinia virus-based reverse genetic system was established for the generation of recombinant human coronavirus 229E. However, it is also applicable to the generation of other coronaviruses, such as the avian infectious bronchitis virus, mouse hepatitis virus, and SARS coronavirus.


title: Shutoff of Host Gene Expression in Influenza A Virus and Herpesviruses: Similar Mechanisms and Common Themes

text: The ability to shut off host gene expression is a shared feature of many viral infections, and it is thought to promote viral replication by freeing host cell machinery and blocking immune responses. Despite the molecular differences between viruses, an emerging theme in the study of host shutoff is that divergent viruses use similar mechanisms to enact host shutoff. Moreover, even viruses that encode few proteins often have multiple mechanisms to affect host gene expression, and we are only starting to understand how these mechanisms are integrated. In this review we discuss the multiplicity of host shutoff mechanisms used by the orthomyxovirus influenza A virus and members of the alpha- and gamma-herpesvirus subfamilies. We highlight the surprising similarities in their mechanisms of host shutoff and discuss how the different mechanisms they use may play a coordinated role in gene regulation.


title: Isolated HE-protein from hemagglutinating encephalomyelitis virus and bovine coronavirus has receptor-destroying and receptor-binding activity

text: Abstract Bovine coronavirus (BCV) and hemagglutinating encephalomyelitis virus (HEV) from swine were found to grow to high titers in MDCK I cells, a subline of Madin Darby canine kidney cells. Virus grown in these cells was used to isolate and purify the HE-protein. This protein has been shown recently to have acetylesterase activity and to function as the receptor-destroying enzyme of BCV. Here we show that HEV contains this enzyme, too. The glycoproteins were solubilized by treatment of virions with octylglucoside. Following centrifugation through a sucrose gradient the surface proteins S and HE (hemagglutinin-esterase) were obtained in purified form. After removal of the detergent by dialysis, HE formed rosettes as shown by electron microscopy. The purified HE protein retained acetylesterase activity and was able to function as a receptor-destroying enzyme rendering red blood cells resistant against agglutination by both coronaviruses. HE protein released from the viral membrane failed to agglutinate red blood cells. However, it was found to recognize glycoconjugates containing N-acetyl-9-O-acetylneuraminic acid as indicated by a binding assay with rat serum proteins blotted to nitrocellulose and by its ability to inhibit the hemagglutinating activity of BCV, HEV, and influenza C virus. The purified enzyme provides a useful tool for analyzing the cellular receptors for coronaviruses.


title: Seven recommendations to rescue the patients and reduce the mortality from COVID-19 infection: An immunological point of view

text: Now COVID-19 is causing a severe public health emergency and the mortality is rapidly increasing all over the world. In the current pandemic era, although there have been many efforts to diagnose a number of patients with symptoms or close contacts, there is no definite guideline for the initial therapeutic approach for them and therefore, many patients have been dying due to a hyperinflammatory immunological reaction labeled as “cytokine storm”. Severe patients are hospitalized and the treatment is done, though they have not been established yet. Currently, however, no treatment is provided for those who are isolated at home or shelter until they get severe symptoms, which will increase the harms to the patients. In this review, we discuss some important points dedicated to the management of patients with COVID-19, which should help reducing morbidity and mortality. In this era, we suggest 7 recommendations to rescue the patients and to reduce the morbidity and mortality due to COVID-19 based on the immunological point of view.


title: Risk Factors Associated with Clinical Outcomes in 323 COVID-19 Hospitalized Patients in Wuhan, China

text: BACKGROUND: With evidence of sustained transmission in more than 190 countries, coronavirus disease 2019 (COVID-19) has been declared a global pandemic. Data are urgently needed about risk factors associated with clinical outcomes. METHODS: A retrospective review of 323 hospitalized patients with COVID-19 in Wuhan was conducted. Patients were classified into three disease severity groups (non-severe, severe, and critical), based on initial clinical presentation. Clinical outcomes were designated as favorable and unfavorable, based on disease progression and response to treatments. Logistic regression models were performed to identify risk factors associated with clinical outcomes, and log-rank test was conducted for the association with clinical progression. RESULTS: Current standard treatments did not show significant improvement in patient outcomes. By univariate logistic regression analysis, 27 risk factors were significantly associated with clinical outcomes. Multivariate regression indicated age over 65 years (p<0.001), smoking (p=0.001), critical disease status (p=0.002), diabetes (p=0.025), high hypersensitive troponin I (>0.04 pg/mL, p=0.02), leukocytosis (>10 x 10(9)/L, p<0.001) and neutrophilia (>75 x 10(9)/L, p<0.001) predicted unfavorable clinical outcomes. By contrast, the administration of hypnotics was significantly associated with favorable outcomes (p<0.001), which was confirmed by survival analysis. CONCLUSIONS: Hypnotics may be an effective ancillary treatment for COVID-19. We also found novel risk factors, such as higher hypersensitive troponin I, predicted poor clinical outcomes. Overall, our study provides useful data to guide early clinical decision making to reduce mortality and improve clinical outcomes of COVID-19.


title: Cross-linked Small Polyethylenimines: While Still Nontoxic, Deliver DNA Efficiently to Mammalian Cells in Vitro and in Vivo

text: PURPOSE. Polyethylenimine (PEI) is among the most efficient nonviral gene delivery vectors. Its efficiency and cytotoxicity depend on molecular weight, with the 25-kDa PEI being most efficient but cytotoxic. Smaller PEIs are noncytotoxic but less efficient. Enhancement in gene delivery efficiency with minimal cytotoxicity by cross-linking of small PEIs via potentially biodegradable linkages was explored herein. The hypothesis was that cross-linking would raise the polycation’s effective molecular weight and hence the transfection efficiency, while biodegradable linkages would undergo the intracellular breakdown after DNA delivery and hence not lead to cytotoxicity. Toward this goal, we carried out cross-linking of branched 2-kDa PEI and its 1:1 (w/w) mixture with a linear 423-Da PEI via ester- and/or amide-bearing linkages; the in vitro and in vivo gene delivery efficiency, as well as toxicity to mammalian cells, of the resultant cross-linked polycations were investigated. METHODS. The efficiency of the cross-linked PEIs in delivering in vitro a plasmid containing β-galactosidase gene and their cytotoxicity were investigated in monkey kidney cells (COS-7). Dynamic light scattering was used to compare the relative DNA condensation efficiency of the unmodified and cross-linked PEIs. In vivo gene delivery efficiency was evaluated by intratracheal delivery in mice of the complexes of a luciferase-encoding plasmid and the PEIs and estimating the luciferase expression in the lungs. RESULTS. Cross-linking boosted the gene delivery efficiency of the small PEIs by 40- to 550-fold in vitro; the efficiency of the most potent conjugates even exceeded by an order of magnitude that of the branched 25-kDa PEI. Effective condensation of DNA was evident from the fact that the mean diameter of the complexes of the cross-linked PEIs was some 300 nm with a narrow size distribution, while the complexes of the unmodified small PEIs exhibited a mean size of >700 nm with a very broad size distribution. At concentrations where the 25-kDa PEI resulted in >95% cell death, the conjugates afforded nearly full cell viability. The cross-linked PEIs were 17 to 80 times m ore efficient than the unmodified ones in vivo; furthermore, their efficiencies were up to twice that of the 25-kDa PEI. CONCLUSIONS. Cross-linking of small PEIs with judiciously designed amide- and ester-bearing linkers boosts their gene delivery efficiency both in vitro and in vivo without increasing the cytotoxicity. The high efficiency is dependent on the nature of the linkages and the PEIs used.


title: Clinicopathological and radiographic features in 40 cats diagnosed with pulmonary and cutaneous Rhodococcus equi infection (2012–2018)

text: OBJECTIVES: This retrospective study aimed to describe clinical manifestations, diagnostic options, radiological features, therapeutic plans and outcomes for cats infected with Rhodococcus equi. METHODS: Forty cats aged between 2 months and 11 years old (median 6 months) that were definitively diagnosed with rhodococcosis between 2012 and 2018 were recruited in this study. Medical records were reviewed for information on signalment, history, clinical presentation, diagnostic testing, treatment plans and clinical outcomes. RESULTS: Of the 40 cats, 36 showed the pulmonary form of the disease, with 35 (87.5%) presented with dyspnoea, while four cats presented with only cutaneous lesions. Mean body temperature was 38.7 ± 0.2(°)C. Dyspnoea was noted in 87.5% of the cats. Leukocytosis (58.3%) with band neutrophilia (83.3%), monocytosis (58.3%) and thrombocytopenia (55.5%) were prominent findings in the haematology reports. Hyperproteinaemia (61.1%) with hypoalbuminaemia (22.2%) and hyperglobulinaemia (63.8%) with a low albumin to globulin ratio (38.9%) were prominent features of blood biochemistry reports. An alveolar–interstitial pattern was noted in 75% of pre-thoracocentesis radiographs. Pleural effusion, hepatomegaly, thoracic lymphadenopathy and atelectasis of any lung lobe were seen in 88.9%, 75%, 41.7% and 36.1% of cats, respectively. Overall, the mortality rate was 67.5% in both forms. CONCLUSIONS AND RELEVANCE: Clinicians should be aware that feline rhodococcosis manifests as a pulmonary disease at a much higher rate than previously reported. Further studies are required to address the epidemiology, pathophysiology, disease management and prognosis of feline rhodococcosis. The role of immunosuppression as a predisposing factor in feline rhodococcosis requires further investigation.


title: Astragalin inhibits autophagy-associated airway epithelial fibrosis

text: BACKGROUND: Fibrotic remodeling of airway and lung parenchymal compartments is attributed to pulmonary dysfunction with an involvement of reactive oxygen species (ROS) in chronic lung diseases such as idiopathic pulmonary fibrosis and asthma. METHODS: The in vitro study elucidated inhibitory effects of astragalin, kaempferol-3-O-glucoside from leaves of persimmon and green tea seeds, on oxidative stress-induced airway fibrosis. The in vivo study explored the demoting effects of astragalin on epithelial to mesenchymal transition in BALB/c mice sensitized with ovalbumin (OVA). RESULTS: The exposure of 20 μM H(2)O(2) for 72 h accelerated E-cadherin loss and vimentin induction in airway epithelial BEAS-2B cells, which was reversed by non-toxic astragalin at 1–20 μM. Astragalin allayed the airway tissue levels of ROS and vimentin enhanced by OVA challenge. Collagen type 1 production increased in H(2)O(2)–exposed epithelial cells and collagen fiber deposition was observed in OVA-challenged mouse airways. This study further investigated that the oxidative stress-triggered autophagic regulation was responsible for inducing airway fibrosis. H(2)O(2) highly enhanced the expression induction of the autophagy-related beclin-1 and light chains 3A/B (LC3A/B) within 4 h and astragalin blocked such induction by H(2)O(2). This compound deterred the ROS-promoted autophagosome formation in BEAS-2B cells. Consistently, in OVA-sensitized mice the expression of beclin-1 and LC3A/B was highly induced, and oral administration of astragalin suppressed the autophagosome formation with inhibiting the induction of these proteins in OVA-challenged airway subepithelium. Induction of autophagy by spermidine influenced the epithelial induction of E-cadherin and vimentin that was blocked by treating astragalin. CONCLUSION: These results demonstrate that astragalin can be effective in allaying ROS-promoted bronchial fibrosis through inhibiting autophagosome formation in airways.


title: Using the Kalman filter with ARIMA for the COVID-19 pandemic dataset of Pakistan

text: The current pandemic of the Novel Corona virus (COVID-19) has resulted in multifold challenges related to health, economy, and society, etc. for the entire world. Many mathematical epidemiological models have been tried for the available data of the COVID-19 pandemic with the core objective to observe the trend and trajectories of infected cases, recoveries, and deaths, etc. However, these models have their own assumptions and parameters and vary with regional demography. This article suggests the use of a more pragmatic approach of the Kalman filter with the Autoregressive Integrated Moving Average (ARIMA) models in order to obtain more precise forecasts for the figures of prevalence, active cases, recoveries, and deaths related to the COVID-19 outbreak in Pakistan.


Rules on isolation rooms for suspected covid-19 cases in GP surgeries to be relaxed.


Enteric viruses in hospital-acquired infection


title: An Illustration of SARS‐CoV‐2 Dissemination Within a Skilled Nursing Facility Using Heat Maps

text: OBJECTIVES: To illustrate dissemination and asymptomatic transmission of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) during a skilled nursing facility (SNF) outbreak. DESIGN: Case report. SETTING AND PARTICIPANTS: Residents of a 150‐bed SNF. MEASUREMENTS: Heat maps generated by the SNF's infection prevention team to track staff and resident symptoms and SARS‐CoV‐2 test results to identify infection patterns. RESULTS: The SNF experienced a severe outbreak of SARS‐CoV‐2 early in the pandemic. The initial cluster of residents with symptoms and the first confirmed case occurred on the SNF's dementia care unit. The insufficient availability and prolonged turnaround time of testing for both residents and staff at the outset of the outbreak prevented timely and accurate identification and cohorting of cases. Despite extensive other infection control measures being in place, SARS‐CoV‐2 disseminated widely through the facility within 3 weeks of the first confirmed case, resulting in significant morbidity and mortality. CONCLUSION: Early, rapid, universal SARS‐CoV‐2 testing of both SNF residents and staff at the outset of an outbreak and then repeatedly thereafter is critical to mitigate viral transmission. This will become even more important as states relax stay‐at‐home orders and SNF staff intermingle with communities that are increasingly mobile. Increased testing will inevitably result in more staff testing positive and having to self‐quarantine at home, meaning that states must partner with SNFs and other long‐term care providers to coordinate and support strategic staffing reserves that can supplement current frontline staff.


title: Air pollution and case fatality of SARS in the People's Republic of China: an ecologic study

text: BACKGROUND: Severe acute respiratory syndrome (SARS) has claimed 349 lives with 5,327 probable cases reported in mainland China since November 2002. SARS case fatality has varied across geographical areas, which might be partially explained by air pollution level. METHODS: Publicly accessible data on SARS morbidity and mortality were utilized in the data analysis. Air pollution was evaluated by air pollution index (API) derived from the concentrations of particulate matter, sulfur dioxide, nitrogen dioxide, carbon monoxide and ground-level ozone. Ecologic analysis was conducted to explore the association and correlation between air pollution and SARS case fatality via model fitting. Partially ecologic studies were performed to assess the effects of long-term and short-term exposures on the risk of dying from SARS. RESULTS: Ecologic analysis conducted among 5 regions with 100 or more SARS cases showed that case fatality rate increased with the increment of API (case fatality = - 0.063 + 0.001 * API). Partially ecologic study based on short-term exposure demonstrated that SARS patients from regions with moderate APIs had an 84% increased risk of dying from SARS compared to those from regions with low APIs (RR = 1.84, 95% CI: 1.41–2.40). Similarly, SARS patients from regions with high APIs were twice as likely to die from SARS compared to those from regions with low APIs. (RR = 2.18, 95% CI: 1.31–3.65). Partially ecologic analysis based on long-term exposure to ambient air pollution showed the similar association. CONCLUSION: Our studies demonstrated a positive association between air pollution and SARS case fatality in Chinese population by utilizing publicly accessible data on SARS statistics and air pollution indices. Although ecologic fallacy and uncontrolled confounding effect might have biased the results, the possibility of a detrimental effect of air pollution on the prognosis of SARS patients deserves further investigation.


title: Interplay of foot-and-mouth disease virus, antibodies and plasmacytoid dendritic cells: virus opsonization under non-neutralizing conditions results in enhanced interferon-alpha responses

text: Foot-and-mouth disease virus (FMDV) is a highly infectious member of the Picornaviridae inducing an acute disease of cloven-hoofed species. Vaccine-induced immune protection correlates with the presence of high levels of neutralizing antibodies but also opsonising antibodies have been proposed as an important mechanism of the immune response contributing to virus clearance by macrophages and leading to the production of type-I interferon (IFN) by plasmacytoid dendritic cells (pDC). The present study demonstrates that the opsonising antibody titres mediating enhanced IFN-α responses in pDC were similar to neutralizing titres, when antigenically related viruses from the same serotype were employed. However, sera cross-reacted also with non-neutralized isolates of multiple serotypes, when tested in this assay. Both uncomplexed virus and immune complexed virus stimulated pDC via Toll-like receptor 7. An additional finding of potential importance for strain-specific differences in virulence and/or immunogenicity was that pDC activation by FMDV strongly differed between viral isolates. Altogether, our results indicate that opsonising antibodies can have a broader reactivity than neutralizing antibodies and may contribute to antiviral responses induced against antigenically distant viruses.


docid: vyyboega

title: Disaster incubation, cumulative impacts and the urban/ex-urban/rural dynamic

text: Abstract This article explores environmental impacts and risks that can accumulate in rural and ex-urban areas and regions and their relation to urban and global development forces. Two Southern Ontario cases are examined: an area level water disaster and cumulative change at the regional level. The role of disaster incubation analysis and advanced environmental assessment tools are discussed in terms of their potential to contribute to more enlightened and effective assessment and planning processes. It is concluded that conventional approaches to EA and planning are characteristically deficient in addressing the full range of impacts and risks, and particularly those originating from pathogens, dispersed and insidious sources. Rigorous application of disaster incubation analysis and more advanced forms of EA has considerable potential to influence a different pattern of planning and decision making.


title: Defining atypical croup: A case report and review of the literature

text: Abstract Background Croup is a common respiratory illness in children. It presents with a barky cough, stridor and hoarseness occurring secondary to inflammation of the subglottis and larynx. The clinical course of croup is well-described, however atypical presentations pose a diagnostic and management challenge. Objectives This case report and systematic review aims to synthesize the published literature on the definition, diagnosis and treatment of atypical croup. Study selection Peer-reviewed journal publications in Ovid MEDLINE® and EMBASE from inception to January 1, 2019 in English, focusing on pediatric patients (<18 years of age) with diagnoses of atypical croup. Data extraction Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results Twelve studies involving 670 patients ranging from 6 months to 11 years of age presenting with atypical croup were selected. A variety of definitions of atypical croup were identified based on recurrence, duration of symptoms, severity, and etiology. Data on the incidence of atypical croup, the overall rates of intubation and tracheostomy, and patient characteristics leading to definitive airway management were not clearly characterized. Limitations All studies were case series, case reports or retrospective chart reviews. Conclusions Atypical croup is a poorly defined clinical entity that is used to describe recurrent, refractory, or croup-like illness that follows an uncharacteristic natural history. Our case presentation and accompanying literature review highlights the variable, but limited, information available on the diagnosis of atypical croup. Given the commonality of its use in clinical practice, we propose some guidelines around the use of the term ‘atypical croup’ as well as a management algorithm.


title: Endogenous annexin A1 counter-regulates bleomycin-induced lung fibrosis

text: BACKGROUND: The balancing functions of pro/anti-inflammatory mediators of the complex innate responses have been investigated in a variety of experimental inflammatory settings. Annexin-A1 (AnxA1) is one mediator of endogenous anti-inflammation, affording regulation of leukocyte trafficking and activation in many contexts, yet its role in lung pathologies has been scarcely investigated, despite being highly expressed in lung cells. Here we have applied the bleomycin lung fibrosis model to AnxA1 null mice over a 21-day time-course, to monitor potential impact of this mediator on the control of the inflammatory and fibrotic phases. RESULTS: Analyses in wild-type mice revealed strict spatial and temporal regulation of the Anxa1 gene, e.g. up-regulation in epithelial cells and infiltrated granulocytes at day 7, followed by augmented protein levels in alveolar macrophages by day 21. Absence of AnxA1 caused increases in: i) the degree of inflammation at day 7; and ii) indexes of fibrosis (assessed by deposition of hydroxyproline in the lung) at day 7 and 21. These alterations in AnxA1 null mice were paralleled by augmented TGF-β1, IFN-γ and TNF-α generation compared to wild-type mice. Finally, treatment of wild type animals with an AnxA1 peptido-mimetic, given prophylactically (from day 0 to 21) or therapeutically (from day 14 onward), ameliorated both signs of inflammation and fibrosis. CONCLUSION: Collectively these data reveal a pathophysiological relevance for endogenous AnxA1 in lung inflammation and, more importantly, fibrosis, and may open new insights for the pharmacological treatment of lung fibrosis.


title: Coptidis Rhizoma: a comprehensive review of its traditional uses, botany, phytochemistry, pharmacology and toxicology

text: Context: Coptidis rhizome (CR), also known as Huanglian in Chinese, is the rhizome of Coptis chinensis Franch., C. deltoidea C.Y. Cheng et Hsiao, or C. teeta Wall (Ranunculaceae). It has been widely used to treat bacillary dysentery, diabetes, pertussis, sore throat, aphtha, and eczema in China. Objectives: The present paper reviews the latest advances of CR, focusing on the botany, phytochemistry, traditional usages, pharmacokinetics, pharmacology and toxicology of CR and its future perspectives. Methods: Studies from 1985 to 2018 were reviewed from books; PhD. and MSc. dissertations; the state and local drug standards; PubMed; CNKI; Scopus; the Web of Science; and Google Scholar using the keywords Coptis, Coptidis Rhizoma, Huanglian, and goldthread. Results: Currently, 128 chemical constituents have been isolated and identified from CR. Alkaloids are the characteristic components, together with organic acids, coumarins, phenylpropanoids and quinones. The extracts/compounds isolated from CR cover a wide pharmacological spectrum, including antibacterial, antivirus, antifungal, antidiabetic, anticancer and cardioprotective effects. Berberine is the most important active constituent and the primary toxic component of CR. Conclusions: As an important herbal medicine in Chinese medicine, CR has the potential to treat various diseases. However, further research should be undertaken to investigate the clinical effects, toxic constituents, target organs and pharmacokinetics, and to establish criteria for quality control, for CR and its related medications. In addition, the active constituents, other than alkaloids, in both raw and processed products of CR should be investigated.


title: An Analysis of Regulatory T-Cell and Th-17 Cell Dynamics during Cytomegalovirus Replication in Solid Organ Transplant Recipients

text: BACKGROUND: CMV-specific T-cells are crucial to control CMV-replication post-transplant. Regulatory T-cells (T-regs) are associated with a tolerant immune state and may contribute to CMV-replication. However, T-cell subsets such as T-regs and IL-17 producing T-cells (Th-17) are not well studied in this context. We explored T-regs and Th-17 frequencies during CMV-replication after transplantation. METHODS: We prospectively evaluated 30 transplant patients with CMV-viremia. We quantified CMV-specific CD4(+) and CD8(+) T-cells, T-regs (CD4(+)CD25(+)FoxP3(+)) and Th-17 frequencies using flow-cytometry and followed patients requiring anti-viral treatment. Two subsets were compared: anti-viral treatment requirement (n = 20) vs. spontaneous clearance of viremia (n = 10). RESULTS: Higher initial CMV-specific CD4(+) T-cells and lower T-regs were observed in patients with spontaneous clearance (p = 0.043; p = 0.021 respectively). Using a ratio of CMV-specific CD4(+) T-cells to T-regs allowed prediction of viral clearance with 80% sensitivity and 90% specificity (p = 0.001). One month after stop of treatment, the same correlation was observed in patients protected from CMV-relapse. The ratio of CMV-specific CD4(+) T-cells to T-regs allowed prediction of relapse with 85% sensitivity and 86% specificity (p = 0.004). Th-17 responses were not correlated with virologic outcomes. CONCLUSIONS: This study provides novel insights into T-regs and Th-17 subpopulations during CMV-replication after transplantation. These preliminary data suggest that measurement of CMV-specific CD4(+) T-cells together with T-regs has value in predicting spontaneous clearance of viremia and relapse.


“What a stay-at-home order means for migrant dairy workers”


title: One train may hide another: Acute cardiovascular diseases could be neglected because of the COVID-19 pandemic

text: Summary Background Coronavirus disease 2019 (COVID-19) is likely to have significant implications for the cardiovascular care of patients. In most countries, containment has already started (on 17 March 2020 in France), and self-quarantine and social distancing are reducing viral contamination and saving lives. However, these considerations may only be the tip of the iceberg; most resources are dedicated to the struggle against COVID-19, and this unprecedented situation may compromise the management of patients admitted with cardiovascular conditions. Aim We aimed to assess the effect of COVID-19 containment measures on cardiovascular admissions in France. Methods We asked nine major cardiology centres to give us an overview of admissions to their nine intensive cardiac care units for acute myocardial infarction or acute heart failure, before and after containment measures. Results Before containment (02–16 March 2020), the nine participating intensive cardiac care units admitted 4.8±1.6 patients per day, versus 2.6±1.5 after containment (17–22 March 2020) (rank-sum test P =0.0006). Conclusions We confirm here, for the first time, a dramatic drop in the number of cardiovascular admissions after the establishment of containment. Many hypotheses might explain this phenomenon, but we feel it is time raise the alarm about the risk for patients presenting with acute cardiovascular disease, who may suffer from lack of attention, leading to severe consequences (an increase in the number of ambulatory myocardial infarctions, mechanical complications of myocardial infarction leading to an increase in the number of cardiac arrests, unexplained deaths, heart failure, etc.). Similar consequences can be feared for all acute situations, beyond the cardiovascular disease setting.


title: Coronavirus disease 2019 and transplantation: The combination of lopinavir/ritonavir and hydroxychloroquine is responsible for excessive tacrolimus trough level and unfavorable outcome

text: The ongoing outbreak of coronavirus disease 2019 (COVID‐19) first reported in Wuhan has been declared global public health emergency and a pandemic by the World Health Organization. Faced with this novel coronavirus, scientists have been trying to use drugs that have not been validated by rigorous clinical trials, such as lopinavir/ritonavir (LPV/r) and hydroxychloroquine (HCQ). These drugs may be used tentatively for general population with COVID‐19, but for solid organ transplant (SOT) recipients with long‐term immunosuppressive therapy and drug‐related metabolic diseases, antiviral drugs should be chosen with particular care. Notably, the elderly SOT patients commonly suffer from liver and kidney dysfunction of varying degrees, resulting in worse drug metabolism.


title: A simple, rapid method for preparation of virus isolates from cell culture for electron microscopy

text: A simple procedure for the rapid preparation of virus isolates from cell culture for negative-contrast electron microscopy was devised. Using only conventional centrifugation steps (i.e. without ultracentrifugation), the procedure produced consistent, fine-quality preparations of a variety of virus types differing in size/shape and buoyant density.


title: New World Bats Harbor Diverse Influenza A Viruses

text: Aquatic birds harbor diverse influenza A viruses and are a major viral reservoir in nature. The recent discovery of influenza viruses of a new H17N10 subtype in Central American fruit bats suggests that other New World species may similarly carry divergent influenza viruses. Using consensus degenerate RT-PCR, we identified a novel influenza A virus, designated as H18N11, in a flat-faced fruit bat (Artibeus planirostris) from Peru. Serologic studies with the recombinant H18 protein indicated that several Peruvian bat species were infected by this virus. Phylogenetic analyses demonstrate that, in some gene segments, New World bats harbor more influenza virus genetic diversity than all other mammalian and avian species combined, indicative of a long-standing host-virus association. Structural and functional analyses of the hemagglutinin and neuraminidase indicate that sialic acid is not a ligand for virus attachment nor a substrate for release, suggesting a unique mode of influenza A virus attachment and activation of membrane fusion for entry into host cells. Taken together, these findings indicate that bats constitute a potentially important and likely ancient reservoir for a diverse pool of influenza viruses.


title: Compassionate use of hydroxychloroquine in clinical practice for patients with mild to severe Covid-19 in a French university hospital

text: BACKGROUND: Data from non-randomized studies have suggested that hydroxychloroquine could be an effective therapeutic agent against Covid-19. METHODS: We conducted an observational, retrospective cohort study involving hospitalized adult patients with confirmed, mild to severe Covid-19 in a French university hospital. Patients who received hydroxychloroquine (200mg tid dosage for 10 days) on a compassionate basis in addition to SOCwere compared to patients without contraindications to hydroxychloroquine who received SOCalone. A propensity score-weighted analysis was performed to control for confounders: age, sex, time between symptom onset and admission ≤ 7 days, Charlson comorbidity index, medical history of arterial hypertension, and obesity, NEWS2 score at admission, and pneumonia severity. The primary endpoint was time to unfavorable outcome, defined as: death, admission to an intensive care unit, or decision to withdraw or withhold life-sustaining treatments, whichever came first. RESULTS: Data from 89 patients with laboratory-confirmed Covid-19 were analyzed, 84 of whom were considered in the primary analysis; 38 patients treated with hydroxychloroquine and 46 patients treated with SOCalone. At admission, the mean age of patients was 66 years, the median Charlson comorbidity index was 3, and the median NEWS2 severity score was 3. After propensity score weighting, treatment with hydroxycholoroquine was not associated with a significantly reduced risk of unfavorable outcome (HR 0.90 [0.38; 2.1], p = 0.81). Overall survival was not significantly different between the two groups (HR 0.89 [0.23; 3.47], p = 1) CONCLUSION: In hospitalized adults with Covid-19, no significant reduction of the risk of unfavorable outcomes was observed with hydroxychloroquine in comparison to standard of care. Unmeasured confounders may however have persisted despite careful propensity-weighted analysis and the study might be underpowered. Ongoing controlled trials in patients with varying degrees of initial severity on a larger scale will help determine whether there is a place for hydroxychloroquine in the treatment of Covid-19.


title: Hämophagozytische Lymphohistiozytose bei unspezifischer Virusinfektion

text: Hemophagocytic lymphohistiocytosis (HLH), also known as hemophagocytic syndrome or macrophage activation syndrome within a pre-existing rheumatological disease, remains undiagnosed in over 70% of all cases in intensive care units (ICU) due to the sepsis-like clinical presentation. This report describes the case of a 30-year-old previously healthy male patient who was admitted to the normal infectiology ward of the Charité – Universitätsmedizin Berlin with unclear fever after a 3‑month journey around Asian and South America. The patient was transferred to the ICU after 3 days because of respiratory failure. Due to the immediate diagnostics of HLH and initiation of specific immunosuppressive treatment with dexamethasone, immunoglobulins and anakinra, the patient completely recovered and could finally be discharged after a 2‑week stay in hospital. Furthermore, the current diagnostic and therapeutic options are discussed. Ferritin is a decisive diagnostic marker that should be determined in every patient with unclear organ failure.


Bat pathogens hit the road: But which one?


title: Temperature screening has negligible value for control of COVID‐19

text: OBJECTIVE: To report the incidence of fever among patients who tested positive for SARS‐CoV‐2. METHODS: Retrospective cohort study of patients who tested positive for SARS‐Cov‐2 at a single centre. Temperature at time of testing and on repeat testing within 24 h were collected. RESULTS: At the time of testing, fever was detected (sensitivity) in 16 of 86 (19%; 95% CI: 11–28) episodes of positive tests for SARS‐CoV‐2. With repeat testing, fever was detected in 18 of 75 (24%; 95% CI: 15–35) episodes. CONCLUSIONS: In an Australian hospital, screening for fever lacked sensitivity for detection of people with SARS‐CoV‐2. This article is protected by copyright. All rights reserved.


title: Fever Screening at Airports and Imported Dengue

text: Airport fever screening in Taiwan, July 2003–June 2004, identified 40 confirmed dengue cases. Results obtained by capture immunoglobulin (Ig) M and IgG enzyme-linked immunoassay, real time 1-step polymerase chain reaction, and virus isolation showed that 33 (82.5%) of 40 patients were viremic. Airport fever screening can thus quickly identify imported dengue cases.


title: Apps for a crisis

text: The new coronavirus has many of us stuck at home. The result could fundamentally reshape how we use the internet, writes Annalee Newitz


COVID-19: Wait For A Novel Drug Or Act With The Age Old Drug - Do We Have A Choice?


title: The Response of An Orthopedic Department and Specialty Hospital at the Epicenter of a Pandemic: The NYU Langone Health Experience

text: Abstract As the world grapples with the COVID-19 pandemic, we as healthcare professionals thrive to continue to help our patients, and as orthopedic surgeons this goal is ever more challenging. As part of a major academic tertiary medical center in New York City, the orthopedic department at New York University (NYU) Langone health has evolved and adapted to meet the challenges of the COVID pandemic. In our report, we will detail the different aspects and actions taken by NYU Langone Health as well as NYU Langone orthopedic Hospital and the Orthopedic Department in particular. Among the steps taken, the department has reconfigured its staff’s assignments to help both with the institution’s efforts and our patients’ needs, from reassigning operating room nurses to medical COVID floors to having attending surgeons cover urgent care locations. We have reorganized our residency and fellowship rotations and assignments as well as adapting our educational programs to online learning. While constantly evolving to meet the institution’s and our patient demands, our leadership starts planning for the return to a new “normal”.


title: Weathering the pandemic: How the Caribbean Basin can use viral and environmental patterns to predict, prepare and respond to COVID‐19

text: The 2020 coronavirus pandemic is developing at different paces throughout the world. Some areas, like the Caribbean Basin, have yet to see the virus strike at full force. When it does, there is reasonable evidence to suggest the consequent COVID‐19 outbreaks will overwhelm healthcare systems and economies. This is particularly concerning in the Caribbean as pandemics can have disproportionately higher mortality impacts on lower and middle income countries. Preliminary observations from our team and others suggest that temperature and climatological factors could influence the spread of this novel coronavirus, making spatiotemporal predictions of its infectiousness possible. This review studies geographic and time‐based distribution of known respiratory viruses in the Caribbean Basin in an attempt to foresee how the pandemic will develop in this region. This review is meant to aid in planning short‐ and long‐term interventions to manage outbreaks at the international, national and sub‐national levels in the region. This article is protected by copyright. All rights reserved.


title: Remdesivir in COVID-19: A critical review of pharmacology, pre-clinical and clinical studies

text: BACKGROUND & AIMS: Remdesivir is a broad spectrum anti-viral drug that has shown to inhibit SARS-CoV-2, in vitro and in vivo. In absence of any effective treatment for SARS-CoV-2 infection (COVID-19), remdesivir has been tried for a compassionate use in severe COVID-19. Newer randomized controlled studies that have recently become available, showed a mixed result. We aimed to systematically search the literature to understand the pharmacology and clinical effects of remdesivir in patients with COVID-19. METHODS: We systematically searched the PubMed, ClinicalTrial.Org and MedRxiv database up till May 5, 2020 using specific key words such as “Remdesivir” or ‘GS-5734″ AND “COVID-19” or “SARS-CoV-2” and retrieved all the article published in English language, that have reported the pharmacology and the clinical outcomes of remdesivir in patients with COVID-19. RESULTS: Initial compassionate use of remdesivir has shown a fairly good result, but difficult to quantify, in the absence of control arm. While the very first double-blind, placebo-controlled, randomized trial conducted in Wuhan, did not find any significant benefit compared to the control, the preliminary result of another similar multi-country trial has shown a significant faster time to recovery but without any difference in mortality. CONCLUSIONS: Remdesivir has shown a mixed result in patients with COVID-19 with an acceptable side effect. However, jury is still out while awaiting the results from the forthcoming trials.


docid: creoyran

title: Structural basis for the function of anti-idiotypic antibody in immune memory

text: Abstract We had earlier proposed a hypothesis to explain the mechanism of perpetuation of immunological memory based on the operation of idiotypic network in the complete absence of antigen. Experimental evidences were provided for memory maintenance through anti-idiotypic antibody (Ab2) carrying the internal image of the antigen. In the present work, we describe a structural basis for such memory perpetuation by molecular modeling and structural analysis studies. A three-dimensional model of Ab2 was generated and the structure of the antigenic site on the hemagglutinin protein H of Rinderpest virus was modeled using the structural template of hemagglutinin protein of Measles virus. Our results show that a large portion of heavy chain containing the CDR regions of Ab2 resembles the domain of the hemagglutinin housing the epitope regions. The similarity demonstrates that an internal image of the H antigen is formed in Ab2, which provides a structural basis for functional mimicry demonstrated earlier. This work brings out the importance of the structural similarity between a domain of hemagglutinin protein to that of its corresponding Ab2. It provides evidence that Ab2 is indeed capable of functioning as surrogate antigen and provides support to earlier proposed relay hypothesis which has provided a mechanism for the maintenance of immunological memory.


title: MicroRNA profiling in paired left and right eyes, lungs, and testes of normal mice

text: Abstract Physiological and pathophysiological differences widely exist in paired organ systems. However, the molecular basis for these differences remain largely unknown. We previously reported that there exist differentially expressed miRNAs (DEMs) in the left and right kidneys of normal mice. Here, we identified the DEMs in the left and right eyes, lungs and testes of normal mice via RNA Sequencing. As a result, we identified 26 DEMs in eyes, with 23 higher and 3 lower in the left eyes compared with right eyes, 21 DEMs in lungs, with 15 higher and 6 lower in the left lungs compared with right lungs; and 54 DEMs in testes, with 6 higher and 48 lower in the left testes compared with right ones. Ten miRNAs were further examined by quantitative PCR assays, and seven of these were confirmed. In addition, correlation analysis was performed between paired organ miRNA expressions and diverse body fluid miRNA expressions. Finally, we explored the functions and networks of DEMs and performed biological process and pathway enrichment analysis of target genes for DEMs, providing insights into the physiological and pathophysiological differences between the two entities of paired organs.


title: TLRs in pulmonary diseases

text: Abstract Toll-like receptors (TLRs) comprise a clan of proteins involved in identification and triggering a suitable response against pathogenic attacks. As lung is steadily exposed to multiple infectious agents, antigens and host-derived danger signals, the inhabiting stromal and myeloid cells of the lung express an aggregate of TLRs which perceive the endogenously derived damage-associated molecular patterns (DAMPs) along with pathogen associated molecular patterns (PAMPs) and trigger the TLR-associated signalling events involved in host defence. Thus, they form an imperative component of host defence activation in case of microbial infections as well as non-infectious pulmonary disorders such as interstitial lung disease, acute lung injury and airways disease, such as COPD and asthma. They also play an equally important role in lung cancer. Targeting the TLR signalling network would pave ways to the design of more reliable and effective vaccines against infectious agents and control deadly infections, desensitize allergens and reduce inflammation. Moreover, TLR agonists may act as adjuvants by increasing the efficiency of cancer vaccines, thereby contributing their role in treatment of lung cancer too. Overall, TLRs present a compelling and expeditiously bolstered area of research and addressing their signalling events would be of significant use in pulmonary diseases.


title: Adenovirus serotype 7 associated with a severe lower respiratory tract disease outbreak in infants in Shaanxi Province, China

text: BACKGROUND: Pneumonia caused by adenovirus infection is usually severe especially with adenovirus serotype 7 commonly associated with lower respiratory tract disease outbreaks. We reported an outbreak of 70 cases of severe pneumonia with one death of infants in Shaanxi Province, China. Sampling showed adenovirus 7 (Ad7) as the primary pathogen with some co-infections. RESULTS: Two strains of adenovirus and two strains of enterovirus were isolated, the 21 pharynx swabs showed 14 positive amplifications for adenovirus; three co-infections with respiratory syncytial virus, two positive for rhinovirus, one positive for parainfluenza 3, and four negative. Adenovirus typing showed nine of the nine adenovirus positive samples were HAdV-7, three were HAdV-3 and two were too weak to perform sequencing. The entire hexon gene of adenovirus was sequenced and analyzed for the two adenovirus serotype 7 isolates, showing the nucleic acid homology was 99.8% between the two strains and 99.5% compared to the reference strain HAdV-7 (GenBank accession number AY769946). For the 21 acute phase serum samples from the 21 patients, six samples had positives results for ELISA detection of HAdV IgA, and the neutralization titers of the convalescent-phase samples were four times higher than those of the acute-phase samples in nine pairs. CONCLUSIONS: We concluded adenovirus was the viral pathogen, primarily HAdV-7, with some co-infections responsible for the outbreak. This is the first report of an infant pneumonia outbreak caused by adenovirus serotype 7 in Shaanxi Province, China.


title: An updated min-review on environmental route of the SARS-CoV-2 transmission

text: The risk of newly emerging diseases is constantly present in a world where changes occur significantly in climatic, commercial, and ecological conditions, in addition to the development of biomedical investigations in new situations. An epidemic respiratory disease instigated by a new coronavirus was initially identified in and has resulted in the current global dissemination. This viral strain and its related disease has been termed “SARS-CoV-2” and “coronavirus disease 2019” (abbreviated “COVID-19” or “2019-nCoV”), respectively, which is transmitted simply between individuals. The World Health Organization (WHO) announced the COVID-19 outburst as a pandemic on March 11, which necessitates a cooperative endeavour globally for mitigating the spread of COVID-19. The absence of previous, and minimum present-day information, particularly concerning the path of contagion have precluded the control of this disease. The present article, therefore, describes the SARS-CoV-2 paths of contagion such as drinking water, solid waste, sewer water, ambient air, and the rest of emerging likely paths.


title: Generation and Selection of Coronavirus Defective Interfering RNA with Large Open Reading Frame by RNA Recombination and Possible Editing

text: Abstract All of the coronavirus defective interfering (DI) RNAs analyzed thus far contain an open reading frame (ORF) from which DI RNA-specific protein(s) are translated, although the function of the DI-specific protein and the significance of the ORF are not known. A complete cDNA clone of a mouse hepatitis virus (MHV) DI RNA, NE-1, containing a single nucleotide deletion in the 5′ region of the ORF was obtained and analyzed. Due to this single nucleotide deletion, a DI-specific protein of 7.5-kDa was made from NE-1, in contrast to the 88-kDa protein made from the wild-type DI RNA. NE-1 RNA was efficiently replicated after transfection into MHV-infected cells. However, after one passage of NE-1 RNA-containing virus, the 88-kDa wild-type protein was synthesized, indicating that the large ORF was restored during NE-1 DI RNA replication. Sequence analysis of NE-1 DI RNA from infected cells demonstrated that in approximately half of the DI RNA population, the ORF was restored by RNA recombination between NE-1 DI RNA and helper virus genomic sequence. The sequences of other DI RNAs contained an additional nontemplated A̱ at the five-A̱ sequence nine nucleotides upstream of the deletion site, resulting in a stretch of six consecutive A̱ s. In these "edited"-type DI RNAs, the original nucleotide deletion was maintained and no RNA recombination was observed. This "editing" produced an ORF of the same size as the wild-type DI RNA. We conclude that the DI RNA with a large ORF has a selective advantage. There was no significant difference in replication efficiency among these RNAs when they replicated alone. However, cotransfection of two DI RNA species and time course experiments suggested that homologous interference and other mechanism(s) during the early stage of virus multiplication are responsible for the accumulation of DI RNAs containing the large ORF.


title: Hazards of the Health Care Sector: Looking Beyond Infectious Disease

text: Abstract Background Possessing every hazard class, the health care sector poses significant health threats to its workforce in both high-resource settings and low- and middle-income countries (LMICs). Objectives The aim of this paper was to examine the applicability of the classical hierarchy of hazard control technologies in resource-constrained health care settings. Methods Using a biologic and chemical hazard example, the hazard control hierarchy was applied for risk mitigation. Findings Even when resource constraints force a reordered selection of hazard control elements, risk reduction can be achieved across a variety of hazard classes. Conclusion For LMICs with limited resources, the hazard control hierarchy can be effectively employed, although the selection of methods may be reordered, to achieve significant hazard control. Such prevention strategies can thereby strengthen and sustain a critical pillar of the health system, its workforce.


title: Engineering a stable CHO cell line for the expression of a MERS-coronavirus vaccine antigen

text: Middle East respiratory syndrome coronavirus (MERS-CoV) has infected at least 2,040 patients and caused 712 deaths since its first appearance in 2012, yet neither pathogen-specific therapeutics nor approved vaccines are available. To address this need, we are developing a subunit recombinant protein vaccine comprising residues 377 to 588 of the MERS-CoV spike protein receptor-binding domain (RBD), which, when formulated with the AddaVax adjuvant, it induces a significant neutralizing antibody response and protection against MERS-CoV challenge in vaccinated animals. To prepare for the manufacture and first-in-human testing of the vaccine, we have developed a process to stably produce the recombinant MERS S377–588 protein in Chinese hamster ovary (CHO) cells. To accomplish this, we transfected an adherent dihydrofolate reductase-deficient CHO cell line (adCHO) with a plasmid encoding S377–588 fused with the human IgG Fc fragment (S377-588-Fc). We then demonstrated the interleukin-2 signal peptide-directed secretion of the recombinant protein into extracellular milieu. Using a gradually increasing methotrexate (MTX) concentration to 5 μM, we increased protein yield by a factor of 40. The adCHO-expressed S377-588-Fc recombinant protein demonstrated functionality and binding specificity identical to those of the protein from transiently transfected HEK293T cells. In addition, hCD26/dipeptidyl peptidase-4 (DPP4) transgenic mice vaccinated with AddaVax-adjuvanted S377-588-Fc could produce neutralizing antibodies against MERS-CoV and survived for at least 21 days after challenge with live MERS-CoV with no evidence of immunological toxicity or eosinophilic immune enhancement. To prepare for large scale-manufacture of the vaccine antigen, we have further developed a high-yield monoclonal suspension CHO cell line.


title: Exhaled Air Dispersion During Oxygen Delivery Via a Simple Oxygen Mask

text: Background Pneumonia viruses such as influenza may potentially spread by airborne transmission. We studied the dispersion of exhaled air through a simple oxygen mask applied to a human patient simulator (HPS) during the delivery of different oxygen flow in a room free of air currents. Methods The HPS represented a 70-kg adult male individual in a semi-sitting position on a hospital bed inclined at 45°. A simple oxygen mask was fitted to the HPS in the normal fashion. The head, neck, and internal airways of the HPS were configured to allow realistic airflow modeling in the airways and around the face. The HPS was programmed to breathe at a respiratory rate of 14 breaths/min with a tidal volume of 0.5 L. Airflow was marked with intrapulmonary smoke for visualization. A leakage jet plume was revealed by a laser light-sheet, and images were captured by high-resolution video. Smoke concentration in the exhaled plume was estimated from the total light intensity scattered by smoke particles. Findings A jet plume of air leaked through the side vents of the simple oxygen mask to lateral distances of 0.2, 0.22, 0.3, and 0.4 m from the sagittal plane during the delivery of oxygen at 4, 6, 8, and 10 L/min, respectively. Coughing could extend the dispersion distance beyond 0.4 m. Conclusion Substantial exposure to exhaled air occurs generally within 0.4 m from patients receiving supplemental oxygen via a simple mask. Health-care workers should take precautions when managing patients with community-acquired pneumonia of unknown etiology that is complicated by respiratory failure.


Baricitinib for COVID-19: a suitable treatment? – Authors' reply


title: Protein composition of tomato spotted wilt virus

text: Abstract Analysis of the protein composition of tomato spotted wilt virus (TSWV), purified by an improved procedure, by polacrylamide gel electrophoresis, revealed three major structural proteins (of MW 84,000, 50,000, and 29,000d) and a minor one of MW 220,000d. The three major proteins constitute about 98% of the total viral protein and all three were shown to be glycoproteins. One of the major proteins (MW 29,000d) and the minor protein were shown to be associated with subviral particles isolated by treatment of virus with the nonionic detergent Nonidet P-40. Only traces of the other two proteins were detected in the subviral particles. Synthesis of virus-induced proteins in TSWV-infected tobacco leaves was studied by labeling infected and healthy tissue with [3H]and [14C]valine, respectively. The labeled tissues were then fractionated into crude subcellular fractions and protein patterns of healthy and infected tissues were compared by coelectrophoresis on polyacrylamide gels. Only one virus-specific protein (of MW 49,000d) was detected in the virus-enriched fractions; this corresponded with the viral structural protein of MW 50,000d.


title: Sterilization of Microorganisms Contaminated Surfaces and its Treatment with Dielectric Barrier Discharge Plasma

text: Dielectric barrier discharge (DBD) is a promising method of producing non-thermal plasma, which is widely used in variety of industrial and biological applications including disinfection/sterilization. Plasma sterilization offers a faster, less toxic and versatile alternative to conventional sterilization techniques. 45 kV, 50 kHz high voltage high-frequency power supply was designed for generating DBD plasma. Experimental studies were conducted using DBD plasma on growth control in algae, breakdown of complex phenols for chemical wastewater treatment and generation of UV, ozone and other reactive species using DBD plasma discharges in ambient air. A portable DBD plasma-based sterilization system is developed for fighting the Covid-19 pandemic. Quartz tube is used as a dielectric medium between copper foil—SS electrodes and 17 kV, 30 kHz pulse is applied across it, which produces intense DBD across SS mesh. This system can sterilize and disinfect the microorganism contaminated surfaces, garments and used disposable protective gears with UV, ozone and short-lived molecules of metastable states and excited chemical species of nitrogen and oxygen produced during the DBD plasma discharges in ambient air.


docid: zokdgmme

title: Herd immunity and a vaccination game: An experimental study

text: Would the affected communities voluntarily obtain herd immunity if a cure for COVID-19 was available? This paper experimentally investigates people’s vaccination choices in the context of a nonlinear public good game. A “vaccination game” is defined in which costly commitments (vaccination) are required of a fraction of the population to reach the critical level needed for herd immunity, without which defectors are punished by the natural contagion of epidemics. Our experimental implementation of a vaccination game in a controlled laboratory setting reveals that endogenous epidemic punishment is a credible threat, resulting in voluntary vaccination to obtain herd immunity, for which the orthodox principle of positive externalities fails to account. The concave nature of the infection probability plays a key role in facilitating the elimination of an epidemic.


title: Co-production in health policy and management: a comprehensive bibliometric review

text: BACKGROUND: Due to an increasingly elderly population, a higher incidence of chronic diseases and higher expectations regarding public service provision, healthcare services are under increasing strain to cut costs while maintaining quality. The importance of promoting systems of co-produced health between stakeholders has gained considerable traction both in the literature and in public sector policy debates. This study provides a comprehensive map of the extant literature and identifies the main themes and future research needs. METHODS: A quantitative bibliometric analysis was carried out consisting of a performance analysis, science mapping, and a scientific collaboration analysis. Web of Science (WoS) was chosen to extract the dataset; the search was refined by language, i.e. English, and type of publication, i.e. journal academic articles and reviews. No time limitation was selected. RESULTS: The dataset is made up of 295 papers ranging from 1994 to May 2019. The analysis highlighted an annual percentage growth rate in the topic of co-production of about 25%. The articles retrieved are split between 1225 authors and 148 sources. This fragmentation was confirmed by the collaboration analysis, which revealed very few long-lasting collaborations. The scientific production is geographically polarised within the EU and Anglo-Saxon countries, with the United Kingdom playing a central role. The intellectual structure consists of three main areas: public administration and management, service management and knowledge translation literature. The co-word analysis confirms the relatively low scientific maturity of co-production applied to health services. It shows few well-developed and central terms, which refer to traditional areas of co-production (e.g. public health, social care), and some emerging themes related to social and health phenomena (e.g. the elderly and chronic diseases), the use of technologies, and the recent patient-centred approach to care (patient involvement/engagement). CONCLUSIONS: The field is still far from being mature. Empirical practices, especially regarding co-delivery and co-management as well as the evaluation of their real impacts on providers and on patients are lacking and should be more widely investigated.


title: General Surgery Operating Room Practice in Patients with COVID-19

text: The virus COVID-19, which emerged in China in December 2019, was announced by the World Health Organization as a pandemic in January 2020 It is known that infection is not severe and may even progress without symptoms in patients who have come into contact with COVID-19 Although various organizations have been informed about how to take measures to protect the patient and the surgeon in case of diseases requiring urgent or elective surgery in people infected with COVID-19 or in cases with high suspicion, there is still no definite judgment between patients, physicians and health authorities In this study, which was prepared with the initiative of the Turkish Surgical Association, we tried to shed light on what should be done and how surgeons should act in patients whose operation is mandatory in light of the available data


title: Respiratory Infection and Airway Reactivity

text: The data reviewed demonstrate that viral and mycoplasma infections induce a spectrum of functional abnormalities in airways. Acute virus infections cause wheezing illnesses in both children and adults. Changes in peripheral airway function during infection with similar organisms are observed in other subjects, usually normal adults. The pathogenesis of these responses is unclear. Pathologic data do show that infection with these pathogens damages the airway epithelium. These changes appear to increase permeability of the respiratory epithelium to protein antigens and consequently may contribute to increased frequency of attacks in asthmatic subjects. In addition, increased mucosal permeability may enhance delivery of inhaled drugs to effector sites in airway walls to induce exaggerated bronchoconstrictor responses in clinical challenge situations. Whether changes in the epithelium during infection, inducing greater antigen entry into the interstitium, results in subsequent development of specific allergy is not known and requires further study.


The Undetermined Destiny of Case Reports in the Era of Sophisticated Medicine


A need for consensus on mortality reporting related to the COVID-19 pandemic in ongoing and future vascular registries and trials.


A brief historical overview of emerging infectious disease response in China and the need for a One Health approach in future responses


Quantification and genotyping in management of virus infection


title: Uncharted Paths*: Hospital Networks in Critical Care

text: Wide variation between hospitals in the quality of critical care lead to many potentially avoidable deaths. Regionalization of critical care is a possible solution; regionalization has been implemented for trauma and neonatal intensive care, and it is under active discussion for medical and cardiac critical care. However, regionalization is only one possible approach to reorganizing critical care services. This commentary introduces the technique of network analysis as a framework for the following: (1) understanding how critically ill patients move between hospitals, (2) defining the roles hospitals play in regional care delivery, and (3) suggesting systematic improvements that may benefit population health. We examined transfers of critically ill Medicare patients in Connecticut in 2005 as a model system. We found that patients are systematically transferred to more capable hospitals. However, we find the standard distinction of hospitals into either “secondary hospitals” or “tertiary hospitals” poorly explains observed transfer patterns; instead, hospitals show a continuum of roles. We further examine the implications of the network pattern in a simulation of quarantine of a hospital to incoming transfers, as occurred during the severe acute respiratory syndrome epidemic. Network perspectives offer new ways to study systems to care for critically ill patients and provide additional tools for addressing pragmatic problems in triage and bed management, regionalization, quality improvement, and disaster preparedness.


title: The use of enzyme-linked immunosorbent assay systems for serology and antigen detection in parvovirus, coronavirus and rotavirus infections in dogs in The Netherlands

text: Abstract Complex trapping blocking (CTB) enzyme-linked immunosorbent assays (ELISAs) and indirect ELISAs for the detection of antibodies to canine parvovirus (CPV), canine coronavirus (CCV) and rotavirus in sera of dogs were established. Double antibody sandwich ELISAs for the detection of CPV-, CCV- and rotavirus antigens in fecal samples were also developed. Both the serological and antigen-detection ELISAs were used to screen samples from dogs in The Netherlands, with or without a history of acute diarrhea. It was shown that the results of the respective serological ELISAs correlated well and that CPV was the major cause of virus-induced acute diarrhea in dogs in The Netherlands.


title: Changes in RT‐PCR test results and symptoms during the menstrual cycle of female individuals infected with SARS‐CoV‐2: Report of two cases

text: The implications of the menstrual cycle for disease susceptibility, development, and severity of acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection are largely unknown. Here, we describe two women infected with SARS‐CoV‐2 whose real‐time reverse transcriptase‐polymerase chain reaction (RT‐PCR) test results and symptoms changed during the menstrual cycle. The first patient developed a fever on the first day of her menstrual period, and again on the first day of her next menstrual period after hospital discharge. RT‐PCR test results were positive during the first menstrual period before admission, but turned negative during hospitalization, and then were positive again during the second menstrual period after hospital discharge. Another one also developed a fever again on the first day of her menstrual period after hospital discharge. RT‐PCR test results were negative before admission and during hospitalization, but turned positive during the first menstrual period after hospital discharge. The cases indicate sex hormones may play an important role in SARS‐CoV‐2 infection. For women with history of exposure to SARS‐CoV‐2, the management protocol should include assessment of the menstrual status.


title: Current landscape of Imaging and the potential role for Artificial intelligence in the management of COVID-19

text: The clinical management of COVID-19 is challenging. Medical imaging plays a critical role in the early detection, clinical monitoring and outcomes assessment of this disease. Chest x-ray radiography (CXR) and computed tomography (CT) are the standard imaging modalities used for the structural assessment of the disease status, while functional imaging (namely, positron emission tomography) has had limited application. Artificial intelligence (AI) can enhance the predictive power and utilization of these imaging approaches and new approaches focusing on detection, stratification and prognostication are showing encouraging results. We review the current landscape of these imaging modalities and AI approaches as applied in COVID-19 management.


title: Resiquimod-Mediated Activation of Plasmacytoid Dendritic Cells Is Amplified in Multiple Sclerosis

text: Background: Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. The cause of multiple sclerosis is unknown but there are several evidences that associate the genetic basis of the disease with environmental causes. An important association between viral infection and development of MS is clearly demonstrated. Viruses have a strong impact on innate immune cells. In particular, myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs), are able to respond to viruses and to activate the adaptive immune response. Methods: In this study we mimic viral infection using synthetic single-strand RNA, Resiquimod, and we compared the response of both DC subsets derived from healthy donors and MS patients by characterizing the expression of costimulatory molecules on the DC surface. Results: We found that pDCs from MS patients express higher levels of OX40-L, HLA-DR, and CD86 than healthy donors. Moreover, we found that blood cells from MS patients and healthy donors upon Resiquimod-stimulation are enriched in a subpopulation of pDCs, characterized by a high amount of costimulatory molecules. Conclusion: Overall, these results indicate that activation of pDCs is enhanced in MS, likely due to a latent viral infection, and that costimulatory molecules expressed on pDCs could mediate a protective response against the viral trigger of autoimmunity.


title: Transient Dominant Selection for the Modification and Generation of Recombinant Infectious Bronchitis Coronaviruses

text: We have developed a reverse genetics system for the avian coronavirus infectious bronchitis virus (IBV) in which a full-length cDNA corresponding to the IBV genome is inserted into the vaccinia virus genome under the control of a T7 promoter sequence. Vaccinia virus as a vector for the full-length IBV cDNA has the advantage that modifications can be introduced into the IBV cDNA using homologous recombination, a method frequently used to insert and delete sequences from the vaccinia virus genome. Here we describe the use of transient dominant selection as a method for introducing modifications into the IBV cDNA. We have used it successfully for the substitution of specific nucleotides, deletion of genomic regions, and the exchange of complete genes. Infectious recombinant IBVs are generated in situ following the transfection of vaccinia virus DNA containing the modified IBV cDNA into cells infected with a recombinant fowlpox virus expressing T7 DNA-dependent RNA polymerase.


title: Respiratory viruses and influenza-like illness: Epidemiology and outcomes in children aged 6 months to 10 years in a multi-country population sample

text: Summary Background Better population data on respiratory viruses in children in tropical and southern hemisphere countries is needed. Methods The epidemiology of respiratory viruses among healthy children (6 months to <10 years) with influenza-like illness (ILI) was determined in a population sample derived from an influenza vaccine trial (NCT01051661) in 17 centers in eight countries (Australia, South East Asia and Latin America). Active surveillance for ILI was conducted for approximately 1 year (between February 2010 and August 2011), with PCR analysis of nasal and throat swabs. Results 6266 children were included, of whom 2421 experienced 3717 ILI episodes. Rhinovirus/enterovirus had the highest prevalence (41.5%), followed by influenza (15.8%), adenovirus (9.8%), parainfluenza and respiratory syncytial virus (RSV) (both 9.7%), coronavirus (5.6%), human metapneumovirus (5.5%) and human bocavirus (HBov) (2.0%). Corresponding incidence per 100 person-years was 29.78, 11.34, 7.03, 6.96, 6.94, 4.00, 3.98 and 1.41. Except for influenza, respiratory virus prevalence declined with age. The incidence of medically-attended ILI associated with viral infection ranged from 1.03 (HBov) to 23.69 (rhinovirus/enterovirus). The percentage of children missing school or daycare ranged from 21.4% (HBov) to 52.1% (influenza). Conclusions Active surveillance of healthy children provided evidence of respiratory illness burden associated with several viruses, with a substantial burden in older children.


title: Three‐dimensional model of a substrate‐bound SARS chymotrypsin‐like cysteine proteinase predicted by multiple molecular dynamics simulations: Catalytic efficiency regulated by substrate binding

text: Severe acute respiratory syndrome (SARS) is a contagious and deadly disease caused by a new coronavirus. The protein sequence of the chymotrypsin‐like cysteine proteinase (CCP) responsible for SARS viral replication has been identified as a target for developing anti‐SARS drugs. Here, I report the ATVRLQ(p1)A(p1')‐bound CCP 3D model predicted by 420 different molecular dynamics simulations (2.0 ns for each simulation with a 1.0‐fs time step). This theoretical model was released at the Protein Data Bank (PDB; code: 1P76) before the release of the first X‐ray structure of CCP (PDB code: 1Q2W). In contrast to the catalytic dyad observed in X‐ray structures of CCP and other coronavirus cysteine proteinases, a catalytic triad comprising Asp187, His41, and Cys145 is found in the theoretical model of the substrate‐bound CCP. The simulations of the CCP complex suggest that substrate binding leads to the displacement of a water molecule entrapped by Asp187 and His41, thus converting the dyad to a more efficient catalytic triad. The CCP complex structure has an expanded active‐site pocket that is useful for anti‐SARS drug design. In addition, this work demonstrates that multiple molecular dynamics simulations are effective in correcting errors that result from low‐sequence‐identity homology modeling. Proteins 2004. © 2004 Wiley‐Liss, Inc.


title: Primum non nocere – Are chloroquine and hydroxychloroquine safe prophylactic/treatment options for SARS-CoV-2 (covid-19)?

text: Chloroquine (CQ) and its analog hydroxychloroquine (HCQ) were recently included in several clinical trials as potential prophylactic and therapeutic options for SARS-COV-2 infection/covid-19. However, drug effectiveness in preventing, treating, or slowing the progression of the disease is still unknown. Despite some initial promising in vitro results, rigorous pre-clinical animal studies and randomized clinical trials have not been performed yet. On the other hand, while the potential effectiveness of CQ/HCQ is, at best, hypothetical, their side effects are factual and most worrisome, particularly when considering vulnerable groups of patients being treated with these drugs. in this comment, we briefly explain the possible mechanisms of action of CQ/HCQ for treating other diseases, possible actions against covid-19, and their potent side effects, in order to reinforce the necessity of evaluating the benefit-risk balance when widely prescribing these drugs for SARS-COV-2 infection/covid-19. We conclude by strongly recommending against their indiscriminate use.


Ivermectina en COVID-19. ¿Argumentum ad ignorantiam?


title: Acute disseminated encephalomyelitis associated with hepatitis B virus reinfection – Consequence or coincidence?

text: Abstract Acute disseminated encephalomyelitis (ADEM) is an idiopathic inflammatory demyelinating disease of the CNS that is particularly difficult to differentiate from the first episode of multiple sclerosis. ADEM typically occurs as a post-infectious phenomenon, and usually presents a monophasic episode, but also includes recurrent and multiphasic forms. We report a case of ADEM associated with hepatitis B virus (HBV) reinfection. After steroid and IV immunoglobulin treatment, neurologic symptoms were improved. We suppose that the HBV reinfection was the cause of ADEM, but possible pathogenetic mechanism is still obscure.


title: The ALPHA Project: An architecture for leveraging public health applications

text: Summary Objective Public health surveillance applications are central to the collection, analysis and dissemination of disease and health information. As these applications evolve and mature, it is evident that many of these applications must address similar requirements, such as policies, security and flexibility. It is important a software architecture is created to meet these requirements. Methods We outline the requirements for a public health surveillance application, and define a set of common components to address these requirements. These components are configured to produce services used in the development of public health applications. Results A layered software architecture, the ALPHA architecture, has been developed to support the development of public health applications. The architecture has been used to build eleven surveillance applications for the Public Health Agency of Canada in the areas of disease surveillance, survey, distributed data collection and inventory management. Conclusions We have found that a software architecture that addresses requirements on policies, security and flexibility facilitates the development of configurable public health applications. By creating this architecture, key success factors, such as reducing cost and time-to-market of applications, adapting to changing surveillance targets and increasing user efficiency are achieved.


docid: mdvkrbrr

title: B-Cell-Mediated Lysis of Cells Infected with the Neurotropic JHM Strain of Mouse Hepatitis Virus

text: Abstract Cells expressing the spike (S) glycoprotein of the neurotropic JHM strain (JHMV) of mouse hepatitis virus (MHV) are susceptible to lysis by B cells derived from naı̈ve mice, including B cells from perforin-deficient mice. Cytolysis requires interaction of the virus receptor and the viral S glycoprotein, is independent of other viral-induced components, and is not a unique property of B cells. Neutralizing anti-S-protein monoclonal antibodies (mAb) and a mAb specific for the viral receptor inhibit lysis. However, cells infected with an MHV strain unable to induce cell–cell fusion are resistant to lysis and lysis of JHMV-infected cells is inhibited by an anti-S-protein nonneutralizing mAb which prevents S-protein-mediated cell fusion. These data suggest that B cells may function as antibody-independent innate immune response during JHMV infection in vivo.


title: Effectiveness of the 2010–2011 seasonal influenza vaccine in preventing confirmed influenza hospitalizations in adults: A case–case comparison, case-control study

text: INTRODUCTION: We estimated influenza vaccine effectiveness (IVE) to prevent laboratory-confirmed influenza-related hospitalizations in patients 18 years old or older during the 2010–2011 influenza season. METHODS: We conducted a prospective case-control study in five hospitals, in Valencia, Spain. Study subjects were consecutive emergency hospitalizations for predefined conditions associated with an influenza-like illness episode <8 days before admission. Patients were considered immunized if vaccinated ≥14 days before influenza-like illness onset. Cases were those with a real time reverse transcriptase polymerase chain reaction (RT-PCR) positive for influenza and controls were RT-PCR positive for other respiratory viruses. Adjusted IVE was estimated as 100 × (1 − adjusted odds ratio). To account for indication bias we computed adjusted IVE for respiratory syncytial virus related hospitalizations. RESULTS: Of 826 eligible hospitalized patients, 102 (12%) were influenza positive and considered cases, and 116 (14%) were positive for other respiratory viruses and considered controls. Adjusted IVE was 54% (95% confidence interval, 11–76%). By subgroup, adjusted IVE was 53% (4–77%) for those with high-risk conditions, 59% (16–79%) for those ≥60 years of age, and, 54% (4–79%) for those ≥60 years of age with high-risk conditions. No influenza vaccine effect was observed against respiratory syncytial virus related hospitalization. CONCLUSION: Influenza vaccination was associated with a significant reduction on the risk of confirmed influenza hospitalization, irrespective of age and high-risk conditions.


title: Perspectives towards antiviral drug discovery against Ebola virus

text: Ebola virus disease (EVD), caused by Ebola viruses, resulted in more than 11 500 deaths according to a recent 2018 WHO report. With mortality rates up to 90%, it is nowadays one of the most deadly infectious diseases. However, no Food and Drug Administration‐approved Ebola drugs or vaccines are available yet with the mainstay of therapy being supportive care. The high fatality rate and absence of effective treatment or vaccination make Ebola virus a category‐A biothreat pathogen. Fortunately, a series of investigational countermeasures have been developed to control and prevent this global threat. This review summarizes the recent therapeutic advances and ongoing research progress from research and development to clinical trials in the development of small‐molecule antiviral drugs, small‐interference RNA molecules, phosphorodiamidate morpholino oligomers, full‐length monoclonal antibodies, and vaccines. Moreover, difficulties are highlighted in the search for effective countermeasures against EVD with additional focus on the interplay between available in silico prediction methods and their evidenced potential in antiviral drug discovery.


title: Molecular basis of COVID-19 relationships in different species: a one health perspective

text: Abstract Outside the Hubei province, China, the mild form of infection and the progressive recover of the COVID-19 patients suggest the intervention of “unconventional” biological mechanisms worthy of attention. Based on the high-homology between the Spike protein epitopes of taxonomically-related coronaviruses, we hypothesized that past contact with infected dogs shield humans against the circulating SARS-CoV-2. Elseways, the recurrent virus exposure over a short time-lapse might result in the Antibody Dependent Enhancement, triggering the violent immune reaction responsible for the severe clinical outcomes observed in the Hubei province. Nevertheless, further experimental studies are desired for a confidential evaluation of the postulated hypotheses.


title: Dual infections of feeder pigs with porcine reproductive and respiratory syndrome virus followed by porcine respiratory coronavirus or swine influenza virus: a clinical and virological study

text: Abstract Dual infections of pigs with porcine reproductive and respiratory syndrome virus (PRRSV) followed by a second common respiratory virus, either porcine respiratory coronavirus (PRCV) or swine influenza virus (SIV), were studied. The aim was to determine if dual infections, as compared to single virus infections, result in enhanced clinical manifestations. It was also examined if PRRSV replication affects replication of PRCV or SIV in the respiratory tract. Groups of conventional 10 week old pigs were inoculated with PRRSV-only (3 pigs), PRCV-only (4 pigs) or SIV-only (4 pigs). Dual inoculations with PRRSV-PRCV (4 pigs) and PRRSV-SIV (3 groups of 4, 4 and 5 pigs) were performed at a 3 day interval. A group of uninoculated control pigs (8 pigs) was included. The infection with PRRSV-only induced a transient fever (40.2°C) at 2 DPI, but no respiratory signs. The PRCV-only infection remained subclinical. The SIV-only infection resulted in a one day fever (40.1°C) with moderate tachypnoea and dyspnoea. Mean weight gain in the virus-inoculated groups was retarded compared with the control group. The PRRSV-PRCV infection induced a 9 day lasting fever (peak 40.9°C) with tachypnoea, dyspnoea and productive coughing. The PRRSV-SIV infection resulted in fever and respiratory signs in all 3 groups. Clinical signs, however, were more pronounced in group 1 than in groups 2 and 3. Pigs of group 1 showed fever during 10 days (peak 41.4°C), tachypnoea, marked dyspnoea with abdominal breathing, and a productive cough. Pigs of groups 2 and 3 had fever for 5 and 3 days (peaks 40.6 and 40.3°C) respectively and mild respiratory disorders. Mean weight gain during 14 DPI of the 2nd virus was 5.9 kg in the PRRSV-PRCV group and 4.0, 6.8 and 6.7 kg in PRRSV-SIV groups 1, 2 and 3 respectively. Mean weight gain during the corresponding period in the PRRSV-only group was 8.6 kg. It was concluded that dual infections with viruses causes more severe disease and growth retardation than single PRRSV infection. PRCV excretion curves were similar in single and dual virus inoculated groups. Excretion of SIV was delayed by 2 days in the dual inoculated pigs. Thus, replication of the second virus is not (PRCV) or only slightly (SIV) affected by a prior infection with PRRSV.


title: Sequence analysis of strains of avian infectious bronchitis coronavirus isolated during the 1960s in the U.K.

text: Sequencing of parts of the spike, small membrane, and integral membrane protein genes of English isolates of avian infectious bronchitis virus (IBV) isolated in the 1960s revealed that they were not the direct ancestors of those isolated in the 1980s.


Analysis of SARS-CoV Receptor Activity of ACE2 Orthologs


title: Efficacy of a Dried Colostrum Powder in the Prevention of Disease in Neonatal Holstein Calves

text: Abstract The efficacy of a dried colostrum powder, DCW Concentrate™, as a colostrum supplement or substitute was tested using four groups of 15 calves. Physical condition and IgG status were examined during the first 30 d of life. Calves were fed the dried colostrum powder (group A), pooled colostrum (group C), or both (groups B and D) 2h after birth. Calves fed 85g of the dried colostrum powder dissolved in 3kg of whole milk (group A) had significantly lower IgG concentrations 24h after birth than calves of the other groups. Administration of 85g of the dried colostrum powder plus 3kg of colostrum (group C) did not lead to significantly higher IgG concentrations 24h after birth than did administration of 3kg of colostrum alone (group B). Calves fed 85g of the dried colostrum powder plus 1.5kg of colostrum (group D) had an IgG concentration at 24h of age that was not significantly different from that of calves given 3kg of colostrum (group B). Morbidity and mortality rates were not significantly different among groups. One calf died in each of groups A and B; no losses occurred in groups C and D. Body weight increase was not significantly different among groups.


title: Therapeutic Options for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection: How Close Are We?

text: Over 1100 cases of MERS-CoV have been reported since it was first identified in June 2012. Clinical presentation ranges from asymptomatic or mild illness to rapidly progressive disease with multi-organ failure and high mortality. Treatment has been largely supportive. A large number of compounds have been shown to have significant in vitro inhibitory activity against MERS-CoV. Until recently, macaques were the only suitable animal models for animal studies, hindering further clinical development of MERS-CoV therapy. However, the recent successful development of MERS-CoV infection model in transduced mice offers opportunities to accelerate clinical development of therapeutic agents for MERS-CoV infection. Currently available evidence supports further clinical investigation of interferon-based treatment regimens for patients with MERS-CoV. Combining interferon with mycophenolate and/or high-dose ribavirin appears especially promising. Monoclonal antibodies against various targets within MERS-CoV Spike protein have yielded encouraging in-vitro results. However, their safety and efficacy require confirmation in animal models and exploratory clinical trials.


SARS-CoV-2 infection in very preterm pregnancy: experiences from two cases


title: Predictors of hand hygiene practice among Saudi nursing students: A cross-sectional self-reported study

text: Summary Hand hygiene is an important component of infection control, which is critical to ensuring patients’ safety in hospitals. Nursing students are regarded as healthcare workers in training and can also be vehicles of cross-contamination within the hospital. Thus, this study aimed to identify the predictors of hand hygiene practice among Saudi nursing students. A descriptive, cross-sectional, self-reported study was conducted among 198 Saudi nursing students. Knowledge, attitude, and practice of hand hygiene were assessed using the WHO Hand Hygiene Knowledge Questionnaire for Health-Care Workers and its adopted scales. A regression analysis was performed to identify the predictors of hand hygiene practice. The respondents demonstrated moderate knowledge of hand hygiene (mean 13.20±2.80). The majority displayed a moderate attitude toward hand hygiene (52.1%), while only a few reported a poor attitude (13.1%). Approximately 68.7%, 29.8%, and 1.5% of the respondents reported moderate, good, and poor practice of hand hygiene, respectively. Having a good attitude toward hand hygiene, being male, being aware that hand hygiene is an effective intervention in preventing healthcare-associated infections (HAIs), attendance at hand hygiene trainings and seminars, and being in the lower academic level of nursing education were identified as predictors of better hand hygiene practice. The importance of ensuring a positive attitude toward hand hygiene and improving awareness of hand hygiene is emphasized, as are educational interventions. Educational interventions should be implemented to reinforce knowledge and instill a positive attitude toward hand hygiene.


docid: ihmjgkfa

title: Studies on the evolution, pathology, and immunity of commercial fattening rabbits affected with epizootic outbreaks of diarrhoeas in Mexico: A case report

text: Abstract Epizootic outbreaks of diarrhoeas have emerged and disseminated in different rabbit farms in Mexico causing great economical losses, during the past years. Seven, 5-weeks-old New Zealand White (NZW) rabbits chosen at random from 35 ill animals that were remitted for postmortem, histopathology, and ultrastructural examinations were studied. Bacteriological and parasitological studies were carried out in three additional ill rabbits of same age. In a field trail 45, 5-weeks-old apparently healthy NZW rabbits were observed daily for sanitary status for a 5-week period. Some of the rabbits did not response to the preventive drug treatment and were therefore, used to study the development of the disease. Clinical signs, gross lesions, and mortality throughout the fattening period were recorded. Eight, 8-weeks-old NZW rabbits who survived an outbreak were assessed for gamma-globulins in serum of the total protein fraction during a 3-week period. Gamma-globulins were also measured in eight free-disease healthy rabbits of same breed and age. Lesions of the small intestine consisted of mucoid enteropathy, lymphocytic plasmocytic enteritis with atrophy and fusion of villi, and hyperplasia of globet cells. Serosal edema was present. Ultrastructural examinations of jejunum and ileum from 3/7 diseased rabbits, revealed enterocytes in apoptosis, mixed with degenerative and/or necrotic changes together with infiltration of lymphocytes, macrophages, neutrophils, and loss of microvillus. There were electron dense structures suggestive of virus particles inside the nuclei and cytoplasm of some enterocytes. There was lymphoid spleen atrophy and proliferation of reticuloendothelial cells in 7/7 rabbits. Interstitial pneumonia in 4/7 rabbits was found. Encephalitozoon cuniculi was detected in the brain of 1/7 rabbits. Escherichia coli were detected in 3/3 cases and Eimeria spp. in 2/3 cases. Mortality rate in the field study was 51.1% and the spread of the disease occur in 9/9 cages. The proportion of gamma-globulins in rabbits who survive an outbreak was much lower (P =0.0001) than free-disease healthy rabbits (8.1±1.0 and 14.0±1.0, respectively). The disease was multifactorial and consisted of sub-acute mucoid enteropathy probably induced by viral infection and aggravated by the proliferation of opportunistic pathogens common to rabbits. This may explain the severe degenerative and necrotic changes observed in the small intestine of diarrhoeic rabbits.


title: Stimulatory role of interleukin 10 in CD8(+) T cells through STATs in gastric cancer

text: CD8(+) T cells are considered to be critical in tumor surveillance and elimination. Increased CD8(+) T cell frequency and function is associated with better prognosis in cancer patients. Interleukin 10 is a cytokine with controversial roles in CD8(+) T cell–mediated anti-tumor immunity. We therefore examined the interleukin 10 expression and consumption in CD8(+) T cells harvested from the peripheral blood and resected tumors of gastric cancer patients of stages II–IV. We found that the gastric cancer patients presented significantly elevated frequencies of interleukin 10–expressing cells in both CD4(+) and CD8(+) T cells compared to healthy controls. But distinctive from the interleukin 10–expressing CD4(+) T cells, which increased in frequency in advanced cancer, the interleukin 10–expressing CD8(+) T cells did not increase with cancer stage in the peripheral blood and actually decreased with cancer stage in resected tumor. Interleukin 10 and interleukin 10 receptor expression was also enriched in interferon gamma–expressing activated CD8(+) T cells. Compared to interleukin 10–nonexpressing CD8(+) T cells, interleukin 10 receptor–expressing CD8(+) T cells secreted significantly elevated interferon gamma levels. Treatment of anti-CD3/CD28-stimulated, purified CD8(+) T cells with interleukin 10 alone could significantly enhance CD8(+) T cell survival, an effect dependent on interleukin 10 receptor expression. Interleukin 10 also increased CD8(+) T cell proliferation synergistically with interferon gamma but not alone. Analysis of downstream signal transducer and activator of transcription molecules showed that interleukin 10 treatment significantly increased the phosphorylation of signal transducer and activator of transcription 3 and signal transducer and activator of transcription 1 to lesser extent. Together, these results demonstrate that interleukin 10 possessed stimulatory roles in activated CD8(+) T cells from gastric cancer patients.


title: Replication of bovine coronavirus in cell line BEK-1 culture

text: Bovine coronavirus readily multiplied and induced marked cytopathic effect in BEK-1 cultures, thus providing a sensitive, practical assay system for viral infectivity and neutralizing antibody and a satisfactory source of the virus.


title: Targeted Strategies for Henipavirus Therapeutics

text: Hendra and Nipah viruses are related emergent paramyxoviruses that infect and cause disease in animals and humans. Disease manifests as a generalized vasculitis affecting multiple organs, but is the most severe in the respiratory and central nervous systems. The high case fatality and person-to-person transmission associated with the most recent NiV outbreaks, and the recent re-emergence of HeV, emphasize the importance and necessity of effective therapeutics for these novel agents. In recent years henipavirus research has revealed a more complete understanding of pathogenesis and, as a consequence, viable approaches towards vaccines and therapeutics have emerged. All strategies target early steps in viral replication including receptor binding and membrane fusion. Animal models have been developed, some of which may prove more valuable than others for evaluating the efficacy of therapeutic agents and regimes. Assessments of protective host immunity and drug pharmacokinetics will be crucial to the further advancement of therapeutic compounds.