title: Tracing open data in emergencies: the case of the COVID‐19 pandemic

text: BACKGROUND: The COVID‐19 pandemic constitutes an ongoing, burning Public Health Emergency of International Concern (PHEIC). In 2015, the World Health Organization (WHO) adopted an open‐data policy recommendation in such situations. OBJECTIVES: The present cross‐sectional meta‐research study aimed to assess the availability of open data and metrics and of articles pertaining to the COVID‐19 outbreak in five high‐impact journals. METHODS: All articles regarding the SARS‐CoV‐2, published in five high impact journals (Ann Intern Med, BMJ, JAMA, NEJM and Lancet) until March 14, 2020 were retrieved. Meta‐data (namely the type of article, number of authors, number of patients, citations, errata, news and social media mentions) were extracted for each article in each journal in a systematic way. Google Scholar and Scopus were used for citations and author metrics respectively, and Altmetrics and PlumX were used for news and social media mentions retrieval. The degree of adherence to the PHEIC open data call was also evaluated. RESULTS: A total of 140 articles were published until March 14, 2020, mostly opinion papers. Sixteen errata followed these publications. The number of authors in each article ranged from 1 to 63, whereas the number of patients with a laboratory‐confirmed SARS‐CoV‐2 infection reached 2,645. The impact of these publications reached a total of 4,210 cumulative crude citations and 342,790 news and social media mentions. Only one publication (0.7%) provided complete open data, while 32 (22.9%) included patient data. CONCLUSIONS: Even though a large number of manuscripts was produced since the pandemic, availability of open data remains restricted.


title: Cell Biology of Membrane Trafficking in Human Disease

text: Understanding the molecular and cellular mechanisms underlying membrane traffic pathways is crucial to the treatment and cure of human disease. Various human diseases caused by changes in cellular homeostasis arise through a single gene mutation(s) resulting in compromised membrane trafficking. Many pathogenic agents such as viruses, bacteria, or parasites have evolved mechanisms to subvert the host cell response to infection, or have hijacked cellular mechanisms to proliferate and ensure pathogen survival. Understanding the consequence of genetic mutations or pathogenic infection on membrane traffic has also enabled greater understanding of the interactions between organisms and the surrounding environment. This review focuses on human genetic defects and molecular mechanisms that underlie eukaryote exocytosis and endocytosis and current and future prospects for alleviation of a variety of human diseases.


title: Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury

text: The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan, Hubei province, and rapidly spread to many provinces in China as well as other countries. Here we report the epidemiological, clinical, laboratory, and radiological characteristics, as well as potential biomarkers for predicting disease severity in 2019-nCoV-infected patients in Shenzhen, China. All 12 cases of the 2019-nCoV-infected patients developed pneumonia and half of them developed acute respiratory distress syndrome (ARDS). The most common laboratory abnormalities were hypoalbuminemia, lymphopenia, decreased percentage of lymphocytes (LYM) and neutrophils (NEU), elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased CD8 count. The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity. ALB, LYM, LYM (%), LDH, NEU (%), and CRP were highly correlated to the acute lung injury. Age, viral load, lung injury score, and blood biochemistry indexes, albumin (ALB), CRP, LDH, LYM (%), LYM, and NEU (%), may be predictors of disease severity. Moreover, the Angiotensin II level in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury. Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s11427-020-1643-8 and is accessible for authorized users.


title: Consecutive yearly outbreaks of respiratory syncytial virus in a haemato-oncology ward and efficacy of infection control measures

text: Summary Background Respiratory syncytial virus (RSV) causes significant respiratory tract infection in immunosuppressed patients. Aim To describe two consecutive yearly outbreaks of RSV in our haemato-oncology ward. Methods Haematology patients presenting with respiratory symptoms were screened by polymerase chain reaction for viral respiratory pathogens using a saline gargle. Findings None of our patients had undergone bone marrow transplant but all had underlying haematological malignancies. Eight patients were affected in the first outbreak (mortality rate: 37.5%) and 12 patients were affected in the second (mortality rate: 8.3%). Extensive infection control measures were implemented in both outbreaks and were successful in preventing further cross-transmission. Conclusion There was significant learning from both outbreaks and actions implemented with the aim of reducing the likelihood and impact of future outbreaks.


Abstracts of the Tenth Conference of the Federation of Infection Societies, 2003


title: A Cryptosporidium PI(4)K inhibitor is a drug candidate for cryptosporidiosis

text: Diarrheal disease is responsible for 8.6% of global child mortality. Recent epidemiological studies found the protozoan parasite Cryptosporidium to be a leading cause of pediatric diarrhea with particularly grave impact on infants and immunocompromised individuals. There is neither a vaccine nor effective treatment. We establish a drug discovery process built on scalable phenotypic assays and mouse models that takes advantage of transgenic parasites. Screening a library of compounds with anti-parasitic activity we identified pyrazolopyridines as inhibitors of Cryptosporidium parvum and C. hominis. Oral treatment with the pyrazolopyridine KDU731 results in potent reduction in intestinal infection of immunocompromised mice. Treatment also leads to rapid resolution of diarrhea and dehydration in neonatal calves, a clinical model of cryptosporidiosis that closely resembles human infection. Our results suggest the Cryptosporidium lipid kinase PI(4)K as a target for pyrazolopyridines and warrant further preclinical evaluation of KDU731 as a drug candidate for the treatment of cryptosporidiosis.


title: The role of infectious agents in the pathogenesis of vasculitis

text: Numerous human studies and animal models have implicated various infectious agents in the pathogenesis of vasculitis in susceptible hosts. However, the link between infection and vasculitis is very complex and only incompletely understood. In fact, different agents can induce the same type of vasculitis, as the case of leukocytoclastic vasculitis exemplifies. Conversely, the same agent can give rise to a panoply of host responses ranging from a clinically silent infection or localized organ involvement to devastating, widespread vasculitis.


title: Chapter Two Targeting Intramembrane Protein–Protein Interactions: Novel Therapeutic Strategy of Millions Years Old

text: Abstract Intramembrane protein–protein interactions (PPIs) are involved in transmembrane signal transduction mediated by cell surface receptors and play an important role in health and disease. Recently, receptor-specific modulatory peptides rationally designed using a general platform of transmembrane signaling, the signaling chain homooligomerization (SCHOOL) model, have been proposed to therapeutically target these interactions in a variety of serious diseases with unmet needs including cancer, sepsis, arthritis, retinopathy, and thrombosis. These peptide drug candidates use ligand-independent mechanisms of action (SCHOOL mechanisms) and demonstrate potent efficacy in vitro and in vivo. Recent studies surprisingly revealed that in order to modify and/or escape the host immune response, human viruses use similar mechanisms and modulate cell surface receptors by targeting intramembrane PPIs in a ligand-independent manner. Here, I review these intriguing mechanistic similarities and discuss how the viral strategies optimized over a billion years of the coevolution of viruses and their hosts can help to revolutionize drug discovery science and develop new, disruptive therapies. Examples are given.


docid: lknyehsa

title: Antiviral activity of animal venom peptides and related compounds

text: Viruses exhibit rapid mutational capacity to trick and infect host cells, sometimes assisted through virus-coded peptides that counteract host cellular immune defense. Although a large number of compounds have been identified as inhibiting various viral infections and disease progression, it is urgent to achieve the discovery of more effective agents. Furthermore, proportionally to the great variety of diseases caused by viruses, very few viral vaccines are available, and not all are efficient. Thus, new antiviral substances obtained from natural products have been prospected, including those derived from venomous animals. Venoms are complex mixtures of hundreds of molecules, mostly peptides, that present a large array of biological activities and evolved to putatively target the biochemical machinery of different pathogens or host cellular structures. In addition, non-venomous compounds, such as some body fluids of invertebrate organisms, exhibit antiviral activity. This review provides a panorama of peptides described from animal venoms that present antiviral activity, thereby reinforcing them as important tools for the development of new therapeutic drugs.


title: Evaluation of the Luminex xTAG Respiratory Viral Panel FAST v2 assay for detection of multiple respiratory viral pathogens in nasal and throat swabs in Vietnam

text: Background: Acute respiratory infections (ARI) are among the leading causes of hospitalization in children ≤5 years old. Rapid diagnostics of viral pathogens is essential to avoid unnecessary antibiotic treatment, thereby slowing down antibiotic-resistance. We evaluated the diagnostic performance of the Luminex xTAG Respiratory Viral Panel FAST v2 against viral specific PCR as reference assays for ARI in Vietnam. Methods: Four hundred and forty two nose and throat swabs were collected in viral transport medium, and were tested with Luminex xTAG Respiratory Viral Panel FAST v2. Multiplex RT-PCR and single RT-PCR were used as references. Results: Overall, sensitivity of the Luminex against reference assays was 91.8%, 95% CI 88.1-94.7 (270/294), whilst 112/6336 (1.8%, 95% CI, 1.4-2.1) of pathogens were detected by the Luminex, but not by reference assays. Frequency of pathogens detected by Luminex and reference assays was 379 and 292, respectively. The diagnostic yield was 66.7% (295/442, 95%CI 62.1-71.1%) for the Luminex assay and 54.1% (239/442, 95% CI, 49.3-58.8%) for reference assays. The Luminex kit had higher yields for all viruses except influenza B virus, respiratory syncytial virus, and human bocavirus. High agreements between both methods [mean (range): 0.91 (0.83-1.00)] were found for 10/15 viral agents. Conclusions: The Luminex assay is a high throughput multiplex platform for rapid detection of common viral pathogens causing ARI. Although the current high cost may prevent Luminex assays from being widely used, especially in limited resource settings where ARI are felt most, its introduction in clinical diagnostics may help reduce unnecessary use of antibiotic prescription.


COVID-19 and Neuroinvasion


title: Inhibitor-Based Therapeutics for Treatment of Viral Hepatitis

text: Viral hepatitis remains a significant worldwide threat, in spite of the availability of several successful therapeutic and vaccination strategies. Complications associated with acute and chronic infections, such as liver failure, cirrhosis and hepatocellular carcinoma, are the cause of considerable morbidity and mortality. Given the significant burden on the healthcare system caused by viral hepatitis, it is essential that novel, more effective therapeutics be developed. The present review attempts to summarize the current treatments against viral hepatitis, and provides an outline for upcoming, promising new therapeutics. Development of novel therapeutics requires an understanding of the viral life cycles and viral effectors in molecular detail. As such, this review also discusses virally-encoded effectors, found to be essential for virus survival and replication in the host milieu, which may be utilized as potential candidates for development of alternative therapies in the future.


docid: zdusggae

title: Is parasite load dependent on host aggregation size? The case of the greater mouse-eared bat Myotis myotis (Mammalia: Chiroptera) and its parasitic mite Spinturnix myoti (Acari: Gamasida)

text: The risk of parasite infection grows with the size of host aggregations, which, in turn, may also depend on host sex and age and the quality of environmental resources. Herein, we studied the relationship between ectoparasitic infections with the wing mite (Spinturnix myoti) and the size of the breeding colonies, sex, age, and body condition index (BCI) of its host, the greater mouse-eared bat (Myotis myotis). The influence of environmental quality in the Carpathian Mountains (Poland) was also examined. We found significant differences in mite abundance and BCI between different breeding aggregations of the greater mouse-eared bat and also between the host sex/age categories. The most heavily infected bats were adult M. myotis females, while young males appeared to be the least infected. The BCI differed significantly between the sexes in young bats (males had a higher BCI than females) and also between colonies. No significant differences in the BCI were found for adult females. We did not find any relationship between the infestation rate of M. myotis, their colony size, the quality of environmental resources (percentage of forest cover around the colony), or the BCI. The prevalence of the various developmental stages of the mites did not differ between the host sex/age categories; however, differences were found in the sex ratios of deutonymphs and adult mites between adult M. myotis females. We predict that parasite load may not be dependent on colony size itself, but mainly on microclimatic factors, which are in turn directly correlated with colony size.


title: Prediction of Virulence Factors Using Bioinformatics Approaches

text: Virulence factors produced by a pathogen are essential for causing disease in the host. They enable the pathogen to establish itself within the host thus enhancing its potential to cause disease and in some instances underlie evasion of host defense mechanisms. Identification of these molecules, especially those of immunological interest and their use in vaccine development are attractive and are among the initial steps of reverse vaccinology. Surface localized virulence factors such as adhesins serve as excellent immunogenic candidates in this regard. In this chapter we have described the bioinformatics approaches for adhesin prediction, which include specific adhesin prediction algorithms.


title: Time-series oligonucleotide count to assign antiviral siRNAs with long utility fit in the big data era

text: Oligonucleotides are key elements of nucleic acid therapeutics such as small interfering RNAs (siRNAs). Influenza and Ebolaviruses are zoonotic RNA viruses mutating very rapidly, and their sequence changes must be characterized intensively to design therapeutic oligonucleotides with long utility. Focusing on a total of 182 experimentally validated siRNAs for influenza A, B and Ebolaviruses compiled by the siRNA database, we conducted time-series analyses of occurrences of siRNA targets in these viral genomes. Reflecting their high mutation rates, occurrences of target oligonucleotides evidently fluctuate in viral populations and often disappear. Time-series analysis of the one-base changed sequences derived from each original target identified the oligonucleotide that shows a compensatory increase and will potentially become the ‘awaiting-type oligonucleotide’ the combined use of this oligonucleotide with the original can provide therapeutics with long utility. This strategy is also useful for assigning diagnostic reverse transcription-PCR primers with long utility.


docid: ilsenpus

title: Genome analysis of canine astroviruses reveals genetic heterogeneity and suggests possible inter-species transmission

text: Abstract Canine astrovirus RNA was detected in the stools of 17/63 (26.9%) samples, using either a broadly reactive consensus RT-PCR for astroviruses or random RT-PCR coupled with massive deep sequencing. The complete or nearly complete genome sequence of five canine astroviruses was reconstructed that allowed mapping the genome organization and to investigate the genetic diversity of these viruses. The genome was about 6.6kb in length and contained three open reading frames (ORFs) flanked by a 5′ UTR, and a 3′ UTR plus a poly-A tail. ORF1a and ORF1b overlapped by 43 nucleotides while the ORF2 overlapped by 8 nucleotides with the 3′ end of ORF1b. Upon genome comparison, four strains (HUN/2012/2, HUN/2012/6, HUN/2012/115, and HUN/2012/135) were more related genetically to each other and to UK canine astroviruses (88–96% nt identity), whilst strain HUN/2012/126 was more divergent (75–76% nt identity). In the ORF1b and ORF2, strains HUN/2012/2, HUN/2012/6, and HUN/2012/135 were related genetically to other canine astroviruses identified formerly in Europe and China, whereas strain HUN/2012/126 was related genetically to a divergent canine astrovirus strain, ITA/2010/Zoid. For one canine astrovirus, HUN/2012/8, only a 3.2kb portion of the genome, at the 3′ end, could be determined. Interestingly, this strain possessed unique genetic signatures (including a longer ORF1b/ORF2 overlap and a longer 3′UTR) and it was divergent in both ORF1b and ORF2 from all other canine astroviruses, with the highest nucleotide sequence identity (68% and 63%, respectively) to a mink astrovirus, thus suggesting a possible event of interspecies transmission. The genetic heterogeneity of canine astroviruses may pose a challenge for the diagnostics and for future prophylaxis strategies.


title: Putative structure and function of ORF3 in SARS coronavirus

text: Abstract Based on molecular modeling techniques we constructed a rational 3D model of ORF3 in SARS coronavirus (SARS-CoV). Our studies suggest that the function of ORF3 could be involved in FAD/NAD binding according to its predicted structure and comparison with other structure neighbors. Furthermore, we identified three pairs of non-canonical N–H⋯π interactions in the structure of ORF3, which can make contributions to the stability of protein structure. These results provide important clues for better understanding of SARS-CoV ORF3 and trying new therapeutic strategies.


docid: asrdjmpi

title: Malaria from hyperendemicity to elimination in Hekou County on China–Vietnam border: an ecological study

text: BACKGROUND: Malaria control and elimination are challenged by diversity and complexity of the determinants on the international border in the Great Mekong Sub-region. Hekou, a Chinese county on the China–Vietnam border, was used to document Chinese experiences and lessons for malaria control and elimination. METHODS: The design was an ecological study. Malaria burden before 1951 and procedures of 64 years (1952–2015) from malaria hyperendemicity to elimination are described. Single and bilinear regression analysis was utilized to analyse the relationship between the annual malaria incidence (AMI) and gross domestic product (GDP), urbanization rate, and banana planting area (BPA). RESULTS: There was a huge malaria burden before 1951. AMI was reduced from 358.62 per 1000 person-years in 1953 to 5.69 per 1000 person-years in 1960. A system of primary health services, comprising three levels of county township hospitals and village health stations maintained malaria control and surveillance activities in changing political and social-economic settings. However, potential under-reported of malaria and market-oriented healthcare led to a malaria epidemic in 1987. Strong political commitment reoriented malaria from a control to an elimination programme. High coverage of malaria intervention and population access to intervention was crucial for malaria control and elimination; meanwhile, AMI was closely associated with socio-economic development, correlation coefficients (R) −0.6845 (95% CI −0.7978, −0.6845) for national GDP, −0.7014 (−0.8093, −0.7014) for national urbanization rate and −0.5563 (−0.7147, −0.3437) for BPA. CONCLUSIONS: Multifactor, including political commitment, effective interventions, social and economic development and changing ecological environment, and the complicated interactions between these factors contribute to malaria elimination in Hekou County. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12936-017-1709-z) contains supplementary material, which is available to authorized users.


13 Health effects of water consumption and water quality


Protection comes at a cost: Doctor's life inside Personal Protection Equipment


title: Marine Predators Algorithm for Forecasting Confirmed Cases of COVID-19 in Italy, USA, Iran and Korea

text: The current pandemic of the new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or COVID-19, has received wide attention by scholars and researchers. The vast increase in infected people is a significant challenge for each country and the international community in general. The prediction and forecasting of the number of infected people (so-called confirmed cases) is a critical issue that helps in understanding the fast spread of COVID-19. Therefore, in this article, we present an improved version of the ANFIS (adaptive neuro-fuzzy inference system) model to forecast the number of infected people in four countries, Italy, Iran, Korea, and the USA. The improved version of ANFIS is based on a new nature-inspired optimizer, called the marine predators algorithm (MPA). The MPA is utilized to optimize the ANFIS parameters, enhancing its forecasting performance. Official datasets of the four countries are used to evaluate the proposed MPA-ANFIS. Moreover, we compare MPA-ANFIS to several previous methods to evaluate its forecasting performance. Overall, the outcomes show that MPA-ANFIS outperforms all compared methods in almost all performance measures, such as Root Mean Squared Error (RMSE), Mean Absolute Error (MAE), Mean Absolute Percentage Error (MAPE), Root Mean Squared Relative Error (RMSRE), and Coefficient of Determination([Formula: see text]). For instance, according to the results of the testing set, the [Formula: see text] of the proposed model is 96.48%, 98.59%, 98.74%, and 95.95% for Korea, Italy, Iran, and the USA, respectively. More so, the MAE is 60.31, 3951.94, 217.27, and 12,979, for Korea, Italy, Iran, and the USA, respectively.


title: Algal lectins as promising biomolecules for biomedical research

text: Lectins are natural bioactive ubiquitous proteins or glycoproteins of non-immune response that bind reversibly to glycans of glycoproteins, glycolipids and polysaccharides possessing at least one non-catalytic domain causing agglutination. Some of them consist of several carbohydrate-binding domains which endow them with the properties of cell agglutination or precipitation of glycoconjugates. Lectins are rampant in nature from plants, animals and microorganisms. Among microorganisms, algae are the potent source of lectins with unique properties specifically from red algae. The demand of peculiar and neoteric biologically active substances has intensified the developments on isolation and biomedical applications of new algal lectins. Comprehensively, algal lectins are used in biomedical research for antiviral, antinociceptive, anti-inflammatory, anti-tumor activities, etc. and in pharmaceutics for the fabrication of cost-effective protein expression systems and nutraceutics. In this review, an attempt has been made to collate the information on various biomedical applications of algal lectins.


title: Respiratory virus surveillance in hospitalised pneumonia patients on the Thailand-Myanmar border

text: BACKGROUND: Pneumonia is a significant cause of morbidity and mortality in the developing world. Viruses contribute significantly to pneumonia burden, although data for low-income and tropical countries are scarce. The aim of this laboratory-enhanced, hospital-based surveillance was to characterise the epidemiology of respiratory virus infections among refugees living on the Thailand-Myanmar border. METHODS: Maela camp provides shelter for ~45,000 refugees. Inside the camp, a humanitarian organisation provides free hospital care in a 158-bed inpatient department (IPD). Between 1st April 2009 and 30th September 2011, all patients admitted to the IPD with a clinical diagnosis of pneumonia were invited to participate. Clinical symptoms and signs were recorded and a nasopharyngeal aspirate (NPA) collected. NPAs were tested for adenoviruses, human metapneumovirus (hMPV), influenza A & B, and RSV by PCR. RESULTS: Seven hundred eight patient episodes (698 patients) diagnosed as pneumonia during the enhanced surveillance period were included in this analysis. The median patient age was 1 year (range: < 1-70), and 90.4% were aged < 5 years. At least one virus was detected in 53.7% (380/708) of episodes. Virus detection was more common in children aged < 5 years old (<1 year: OR 2.0, 95% CI 1.2-3.4, p = 0.01; 1-4 years: OR 1.4, 95% CI 0.8-2.3, p = 0.2). RSV was detected in 176/708 (24.9%); an adenovirus in 133/708 (18.8%); an influenza virus in 68/708 (9.6%); and hMPV in 33/708 (4.7%). Twenty-eight episodes of multiple viral infections were identified, most commonly adenovirus plus another virus. RSV was more likely to be detected in children <5 years (OR 12.3, 95% CI 3.0-50.8, p = 0.001) and influenza viruses in patients ≥5 years (OR 2.8, 95% CI 1.5-5.4, p = 0.002). IPD treatment was documented in 702/708 cases; all but one patient received antimicrobials, most commonly a beta-lactam (amoxicillin/ampicillin +/−gentamicin in 664/701, 94.7%). CONCLUSIONS: Viral nucleic acid was identified in the nasopharynx in half the patients admitted with clinically diagnosed pneumonia. Development of immunisations targeting common respiratory viruses is likely to reduce the incidence of pneumonia in children living refugee camps and similar settings.


Cardiac drugs and outcome in COVID - 19


Attenuated Novel SARS Coronavirus 2 Infection in an Allogeneic Hematopoietic Stem Cell Transplant patient on Ruxolitinib


title: Synthesis and Characterization of H(3)PW(12)O(40) and H(3)PMo(12)O(40) Nanoparticles by a Simple Method

text: In this study H(3)PW(12)O(40)·9H(2)O and H(3)PMo(12)O(40)·6H(2)O (HPA) particles were changed into nano forms by heat-treatment in an autoclave as a simple, repaid, inexpensive and one step method. The particle size of these nanoparticles was around 25 nm. The as-synthesized nanostructures were characterized by dynamic light scattering, X-ray powder diffraction, transmission electron microscopy, Fourier transform infrared spectroscopy and inductively coupled plasma analyzer. Thermal stability of nanoparticles was surveyed by thermal gravimeter analyse. Acidity of prepared nanoparticles was investigated by pyridine adsorption method. Results showed rising acidity by declining particle size of HPA.


title: Nervous system involvement after infection with COVID-19 and other coronaviruses

text: Abstract Viral infections have detrimental impacts on neurological functions, and even to cause severe neurological damage. Very recently, coronaviruses (CoV), especially severe acute respiratory syndrome CoV 2 (SARS-CoV-2), exhibit neurotropic properties and may also cause neurological diseases. It is reported that CoV can be found in the brain or cerebrospinal fluid. The pathobiology of these neuroinvasive viruses is still incompletely known, and it is therefore important to explore the impact of CoV infections on the nervous system. Here, we review the research into neurological complications in CoV infections and the possible mechanisms of damage to the nervous system.


title: Diagnostic Performance of CT and Reverse Transcriptase-Polymerase Chain Reaction for Coronavirus Disease 2019: A Meta-Analysis

text: BACKGROUND: Recent studies have suggested that chest computed tomography (CT) scans could be used as a primary screening or diagnostic tool for coronavirus disease 2019 (COVID-19) in epidemic areas. PURPOSE: To perform a meta-analysis to evaluate diagnostic performance measures, including predictive values, of chest CT and initial reverse transcriptase-polymerase chain reaction (RT-PCR). MATERIALS AND METHODS: MEDLINE and Embase were searched from January 1, 2020 to April 3, 2020 for studies on COVID-19 that reported the sensitivity and/or specificity of CT scans and/or RT-PCR assays. The pooled sensitivity and specificity were estimated by using random-effects models. The actual prevalence (i.e., the proportion of confirmed patients among those tested) in eight countries was obtained from web sources, and the predictive values were calculated. Meta-regression was performed to reveal the effect of potential explanatory factors on the diagnostic performance measures. RESULTS: The pooled sensitivity was 94% (95% CI: 91%, 96%; I(2)=95%) for chest CT and 89% (95% CI: 81%, 94%; I(2)=90%) for RT-PCR. The pooled specificity was 37% (95% CI: 26%, 50%; I(2)=83%) for chest CT. The prevalence of COVID-19 outside China ranged from 1.0% to 22.9%. For chest CT scans, the positive predictive value (PPV) ranged from 1.5% to 30.7%, and the negative predictive value (NPV) ranged from 95.4% to 99.8%. For RT-PCR,the PPV ranged from 47.3% to 96.4%, while the NPV ranged from 96.8% to 99.9%. The sensitivity of CT was affected by the distribution of disease severity, the proportion of patients with comorbidities, and the proportion of asymptomatic patients (all p < 0.05). The sensitivity of RT-PCR was negatively associated with the proportion of elderly patients (p = 0.01). CONCLUSION: Outside of China where there is a low-prevalence of COVID-19 (1-22.9%), chest CT screening of patients with suspected disease had low positive predictive value (1.5-30.7%).


One Health and EcoHealth: the same wine in different bottles?


docid: izzavogm

title: C-reactive protein, procalcitonin, D-dimer, and ferritin in severe coronavirus disease-2019: a meta-analysis

text: BACKGROUND: Patients critically ill with coronavirus disease-2019 (COVID-19) feature hyperinflammation, and the associated biomarkers may be beneficial for risk stratification. We aimed to investigate the association between several biomarkers, including serum C-reactive protein (CRP), procalcitonin (PCT), D-dimer, and serum ferritin, and COVID-19 severity. METHODS: We performed a comprehensive systematic literature search through electronic databases. The outcome of interest for this study was the composite poor outcome, which comprises mortality, acute respiratory distress syndrome, need for care in an intensive care unit, and severe COVID-19. RESULTS: A total of 5350 patients were pooled from 25 studies. Elevated CRP was associated with an increased composite poor outcome [risk ratio (RR) 1.84 (1.45, 2.33), p < 0.001; I(2): 96%] and its severe COVID-19 (RR 1.41; I(2): 93%) subgroup. A CRP ⩾10 mg/L has a 51% sensitivity, 88% specificity, likelihood ratio (LR) + of 4.1, LR- of 0.5, and an area under curve (AUC) of 0.84. An elevated PCT was associated with an increased composite poor outcome [RR 3.92 (2.42, 6.35), p < 0.001; I(2): 85%] and its mortality (RR 6.26; I(2): 96%) and severe COVID-19 (RR 3.93; I(2): 63%) subgroups. A PCT ⩾0.5 ng/ml has an 88% sensitivity, 68% specificity, LR+ of 2.7, LR- of 0.2, and an AUC of 0.88. An elevated D-dimer was associated with an increased composite poor outcome [RR 2.93 (2.14, 4.01), p < 0.001; I(2): 77%], including its mortality (RR 4.15; I(2): 83%) and severe COVID-19 (RR 2.42; I(2): 58%) subgroups. A D-dimer >0.5 mg/L has a 58% sensitivity, 69% specificity, LR+ of 1.8, LR- of 0.6, and an AUC of 0.69. Patients with a composite poor outcome had a higher serum ferritin with a standardized mean difference of 0.90 (0.64, 1.15), p < 0.0001; I(2): 76%. CONCLUSION: This meta-analysis showed that an elevated serum CRP, PCT, D-dimer, and ferritin were associated with a poor outcome in COVID-19. The reviews of this paper are available via the supplemental material section.


title: Genomic relationship of porcine hemagglutinating encephalomyelitis virus to bovine coronavirus and human coronavirus OC43 as studied by the use of bovine coronavirus S gene-specific probes

text: The genomic relationship of porcine hemagglutinating encephalomyelitis virus (HEV) to bovine coronavirus (BCV) and human coronavirus (HCV) strain OC43 was examined by dot blot hybridization assays. Two BCV S gene-specific probes were generated by polymerase chain reaction from the avirulent L9-strain of BCV. Probes were located in the S1 and the S2 region of the peplomeric (S) glycoprotein gene. The S1 probe (726 bp) hybridized with BCV and HCV-OC43, but not with HEV under moderate stringency hybridization conditions (50 °C). Only slight signals were present with mouse hepatitis virus (MHV) and no signals were observed with feline infectious peritonitis virus (FIPV) or canine coronavirus (CCV). At high stringency conditions (60 °C) the S1 probe hybridized with BCV only. Using the S2 probe (680 bp) under moderate strin-gency conditions, hybridization signals were obtained with BCV, HCV-OC43 and HEV (strains 67N, NT9, VW572). The signals obtained by the three HEV strains were altogether weaker than with BCV and HCV-OC43. The S2 probe did not react with MHV, FIPV and CCV. At high stringency the S2-specific probe hybridized with BCV and HCV-OC43 but did not hybridize with HEV. Nucleotide sequence analysis of the region covering the S2 probe in HEV revealed 92.6% nucleotide sequence homology to BCV and 91.9% to HCV-OC43. In contrast, the region covering the S1 probe in HEV could not be amplified using the BCV S1-specific primers. The hybridization and sequencing results thus indicate a closer genomic relationship between BCV and HCV-OC43 than there is between HEV and BCV or HCV-OC43, respectively.


title: Algorithms for interval-valued fuzzy soft sets in emergency decision making based on WDBA and CODAS with new information measure

text: Abstract This paper aims to give deeper insights into decision making problem based on interval-valued fuzzy soft set (IVFSS). Firstly, a new score function for interval-valued fuzzy number is proposed for tackling the comparison problem. Subsequently, the formulae of information measures (distance measure, similarity measure and entropy) are introduced and their transformation relations are pioneered. Then, the objective weights of various parameters are determined via new entropy method, meanwhile, we develop the combined weights, which can show both the subjective information and the objective information. Moreover, we propose three algorithms to solve interval-valued fuzzy soft decision making problem by Weighted Distance Based Approximation (WDBA), COmbinative Distance-based ASsessment (CODAS) and similarity measure. Finally, the effectiveness and feasibility of approaches are demonstrated by a mine emergency decision making problem. The salient features of the proposed methods, compared to the existing interval-valued fuzzy soft decision making methods, are (1) it can obtain the optimal alternative without counterintuitive phenomena; (2) it has a great power in distinguishing the optimal alternative; and (3) it can avoid the parameter selection problems.


title: Co-infection with feline retrovirus is related to changes in immunological parameters of cats with sporotrichosis

text: Feline sporotrichosis due to Sporothrix brasiliensis is frequently severe and often correlated to zoonotic transmission. Feline Immunodeficiency Virus (FIV) and Feline Leukemia Virus (FeLV) cause immunodeficiency in cats; no association has been identified with critical cases of sporotrichosis. Moreover, the cytokine profile in Sporothrix-infected cats and a potential impact of retrovirus co-infections on their immunity is unknown. This study assessed immunological parameters in cats with sporotrichosis with and without FIV or FeLV co-infection. FeLV infection was detected by antigen ELISA and by provirus PCR. FIV infection was investigated through ELISA and Western blot. Cytokine transcription (IFN-γ, IL-4, IL-5, IL-6, IL-10, IL-12, TNF-α) was quantified using RT-qPCR and lymphocyte subpopulations (CD4, CD8, CD5 and CD21) were assessed by flow cytometry. Thirty cats with sporotrichosis were recruited to the study, including three FIV-positive and five FeLV-positive (progressive infection) cats. One cat with regressive FeLV infection was excluded from statistics. In comparison to retrovirus-negative cats, FIV-positive cats and FeLV-positive cats had higher IL-10 levels, FeLV-positive cats had lower IL-4 levels and FIV-positive cats had lower IL-12 levels and a lower CD4+/CD8+ ratio. Remarkably, all cats with poor general condition were FeLV (progressive infection) or FIV-positive, but the retrovirus status was not associated with the sporotrichosis treatment length or outcome. The immunological changes and the more severe clinical presentation observed in cats with retrovirus co-infections encourage future prospective studies that address the impact of these changes on prognostic determinants of feline sporotrichosis and the development of new therapy strategies that control disease spread.


title: Web-based infectious disease surveillance systems and public health perspectives: a systematic review

text: BACKGROUND: Emerging and re-emerging infectious diseases are a significant public health concern, and early detection and immediate response is crucial for disease control. These challenges have led to the need for new approaches and technologies to reinforce the capacity of traditional surveillance systems for detecting emerging infectious diseases. In the last few years, the availability of novel web-based data sources has contributed substantially to infectious disease surveillance. This study explores the burgeoning field of web-based infectious disease surveillance systems by examining their current status, importance, and potential challenges. METHODS: A systematic review framework was applied to the search, screening, and analysis of web-based infectious disease surveillance systems. We searched PubMed, Web of Science, and Embase databases to extensively review the English literature published between 2000 and 2015. Eleven surveillance systems were chosen for evaluation according to their high frequency of application. Relevant terms, including newly coined terms, development and classification of the surveillance systems, and various characteristics associated with the systems were studied. RESULTS: Based on a detailed and informative review of the 11 web-based infectious disease surveillance systems, it was evident that these systems exhibited clear strengths, as compared to traditional surveillance systems, but with some limitations yet to be overcome. The major strengths of the newly emerging surveillance systems are that they are intuitive, adaptable, low-cost, and operated in real-time, all of which are necessary features of an effective public health tool. The most apparent potential challenges of the web-based systems are those of inaccurate interpretation and prediction of health status, and privacy issues, based on an individual’s internet activity. CONCLUSION: Despite being in a nascent stage with further modification needed, web-based surveillance systems have evolved to complement traditional national surveillance systems. This review highlights ways in which the strengths of existing systems can be maintained and weaknesses alleviated to implement optimal web surveillance systems. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-016-3893-0) contains supplementary material, which is available to authorized users.


title: Silencing the cytokine storm: the use of intravenous anakinra in haemophagocytic lymphohistiocytosis or macrophage activation syndrome

text: Summary The term cytokine storm syndromes describes conditions characterised by a life-threatening, fulminant hypercytokinaemia with high mortality. Cytokine storm syndromes can be genetic or a secondary complication of autoimmune or autoinflammatory disorders, infections, and haematological malignancies. These syndromes represent a key area of interface between rheumatology and general medicine. Rheumatologists often lead in management, in view of their experience using intensive immunosuppressive regimens and managing cytokine storm syndromes in the context of rheumatic disorders or infection (known as secondary haemophagocytic lymphohistiocytosis or macrophage activation syndrome [sHLH/MAS]). Interleukin (IL)-1 is pivotal in hyperinflammation. Anakinra, a recombinant humanised IL-1 receptor antagonist, is licenced at a dose of 100 mg once daily by subcutaneous injection for rheumatoid arthritis, systemic juvenile idiopathic arthritis, adult-onset Still's disease, and cryopyrin-associated periodic syndromes. In cytokine storm syndromes, the subcutaneous route is often problematic, as absorption can be unreliable in patients with critical illness, and multiple injections are needed to achieve the high doses required. As a result, intravenous anakinra is used in clinical practice for sHLH/MAS, despite this being an off-licence indication and route of administration. Among 46 patients admitted to our three international, tertiary centres for sHLH/MAS and treated with anakinra over 12 months, the intravenous route of delivery was used in 18 (39%) patients. In this Viewpoint, we describe current challenges in the management of cytokine storm syndromes and review the pharmacokinetic and safety profile of intravenous anakinra. There is accumulating evidence to support the rationale for, and safety of, intravenous anakinra as a first-line treatment in patients with sHLH/MAS. Intravenous anakinra has important clinical relevance when high doses of drug are required or if patients have subcutaneous oedema, severe thrombocytopenia, or neurological involvement. Cross-speciality management and collaboration, with the generation of international, multi-centre registries and biobanks, are needed to better understand the aetiopathogenesis and improve the poor prognosis of cytokine storm syndromes.


title: Free fatty acids induce ER stress and block antiviral activity of interferon alpha against hepatitis C virus in cell culture

text: BACKGROUND: Hepatic steatosis is recognized as a major risk factor for liver disease progression and impaired response to interferon based therapy in chronic hepatitis C (CHC) patients. The mechanism of response to interferon-alpha (IFN-α) therapy under the condition of hepatic steatosis is unexplored. We investigated the effect of hepatocellular steatosis on hepatitis C virus (HCV) replication and IFN-α antiviral response in a cell culture model. METHODS: Sub-genomic replicon (S3-GFP) and HCV infected Huh-7.5 cells were cultured with a mixture of saturated (palmitate) and unsaturated (oleate) long-chain free fatty acids (FFA). Intracytoplasmic fat accumulation in these cells was visualized by Nile red staining and electron microscopy then quantified by microfluorometry. The effect of FFA treatment on HCV replication and IFN-α antiviral response was measured by flow cytometric analysis, Renilla luciferase activity, and real-time RT-PCR. RESULTS: FFA treatment induced dose dependent hepatocellular steatosis and lipid droplet accumulation in the HCV replicon cells was confirmed by Nile red staining, microfluorometry, and by electron microscopy. Intracellular fat accumulation supports replication more in the persistently HCV infected culture than in the sub-genomic replicon (S3-GFP) cell line. FFA treatment also partially blocked IFN-α response and viral clearance by reducing the phosphorylation of Stat1 and Stat2 dependent IFN-β promoter activation. We show that FFA treatment induces endoplasmic reticulum (ER) stress response and down regulates the IFNAR1 chain of the type I IFN receptor leading to defective Jak-Stat signaling and impaired antiviral response. CONCLUSION: These results suggest that intracellular fat accumulation in HCV cell culture induces ER stress, defective Jak-Stat signaling, and attenuates the antiviral response, thus providing an explanation to the clinical observation regarding how hepatocellular steatosis influences IFN-α response in CHC.


title: Viral interactions with the host and microbiota in the intestine

text: This review explores the recent advances that have been made in our understanding of host viral interactions in the intestine. Technical advances have allowed the initial definition of intestinal viromes in a number of species including humans. Important advances in our knowledge of the host response to viral infection have shown that interferon lambda has a role that is unique from type I interferons in the intestine. Lastly, our understanding of virally induced phenotypes has expanded through new studies that show bacteria can play an important role in the outcome of viral infection in the intestine.


title: Treatment of COVID-19 Patients with Convalescent Plasma in Houston, Texas

text: Background: COVID-19 disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread globally, and no proven treatments are available. Convalescent plasma therapy has been used with varying degrees of success to treat severe microbial infections for more than 100 years. Methods: Patients (n=25) with severe and/or life-threatening COVID-19 disease were enrolled at the Houston Methodist hospitals from March 28 to April 14, 2020. Patients were transfused with convalescent plasma obtained from donors with confirmed SARS-CoV-2 infection and had been symptom free for 14 days. The primary study outcome was safety, and the secondary outcome was clinical status at day 14 post-transfusion. Clinical improvement was assessed based on a modified World Health Organization 6-point ordinal scale and laboratory parameters. Viral genome sequencing was performed on donor and recipient strains. Results: At baseline, all patients were receiving supportive care, including anti-inflammatory and anti-viral treatments, and all patients were on oxygen support. At day 7 post-transfusion with convalescent plasma, nine patients had at least a 1-point improvement in clinical scale, and seven of those were discharged. By day 14 post-transfusion, 19 (76%) patients had at least a 1-point improvement in clinical status and 11 were discharged. No adverse events as a result of plasma transfusion were observed. The whole genome sequencing data did not identify a strain genotype-disease severity correlation. Conclusions: The data indicate that administration of convalescent plasma is a safe treatment option for those with severe COVID-19 disease. Randomized, controlled trials are needed to determine its efficacy.


title: 9 Composite nonwovens in medical applications

text: Abstract: This chapter reviews the role of composite nonwovens in medical applications. It covers surgical gowns, clinical wearable products, wipes, wound dressings, pads, swabs, scaffolds for tissue engineering, hernia meshes, filtration materials, and incontinence products. Commercially available, innovatively designed composite nonwovens for various medical applications are improving the quality of life of many people. Specific research needs have been highlighted to further improve the effectiveness of these products. The chapter ends with some perspectives for the use of composite nonwovens in medical applications in the future.


title: The clinical course and its correlated immune status in COVID-19 pneumonia

text: Abstract Objectives To explore the clinical course and its dynamic features of immune status in COVID-19 patients and find predictors correlated with severity and prognosis of COVID-19. Methods The electronic medical records of 204 patients with COVID-19 pneumonia confirmed by nucleic acid testing were retrospectively collected and analyzed. Results All Patients were divided into severe (69) and non-severe group (135). Lymphocyte subsets count, including CD3 + T cell, CD4 + T cell, CD8 + T cell, B cell (CD19+) and NK cell (CD16 + 56+), were significantly lower in severe group (P＜0.001). The dynamic levels of T lymphocytes in severe group were significantly lower from disease onset, but in the improved subgroup the value of T lymphocyte began to increase after about 15-day treatment and finally returned to the normal level. The cut-off value of the counts of CD3+ (576), CD4+ (391) and CD8+ (214) T cell were calculated and indicated significantly high sensitivity and specificity for severity of COVID-19. Conclusion Our results shown that the decrease of CD3+, CD4+ and CD8 + T lymphocyte correlated with the course of patients with COVID-19 pneumonia, especially in severe cases. The level of T lymphocyte could be used as an indicator for prediction of severity and prognosis of patients with COVID-19 pneumonia. The application of glucocorticoid should be cautious in severe cases.


Smoke evacuation, is it important for prevention of COVID‐19?


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title: Ethical concerns for anesthesiologists during an Ebola threat

text: PURPOSE: The World Health Organization has proclaimed the current Ebola outbreak as a public health emergency. If an outbreak of Ebola should occur in Canada, anesthesiologists and anesthesia departments may be called upon to respond. The purpose of this review is to highlight and discuss potential ethical concepts that may be relevant to anesthesiologists. SOURCE: A thorough literature search was conducted using a variety of MEDLINE(®) sources, and we used Stand on Guard for Thee. Ethical Considerations in Preparedness Planning for Pandemic Influenza, a report by The University of Toronto Joint Centre for Bioethics Pandemic Influenza Working Group, as the framework for our review. PRINCIPAL FINDINGS: Two groups of ethical concerns were identified. The first group relates to public health ethics, which analyzes the morality of public health interventions, and the second group relates to medical ethics, particularly to “the duty to care”. The Canadian Medical Association Code of Ethics is vague in the description of duties of physicians who may respond to high-risk contagious diseases. CONCLUSIONS: Government, public health authorities, and anesthesia departments need to be prepared to respond to an outbreak of Ebola. Anesthesiologists have a skill that is suited to treat the complications of Ebola virus disease, and in case they are called for duty, anesthesiologists should be aware of the ethical concerns of treating a highly contagious communicable disease.


title: Prediction of smallpox outbreak and evaluation of control-measure policy in Japan, using a mathematical model

text: Abstract Since the September 1 terrorist attacks and moreover, since the anthrax exposure events in 2001 in the United States, bioterrorism attacks seem to be a real threat. Of course, the public health authorities in Japan have started to prepare control measures for such events. We report here our attempts, using a mathematical model, to estimate outbreak size and to examine the most effective measures; comparing ring vaccination (contact tracing, isolation, and vaccination among contacts) and mass vaccination of the susceptible population in the area. The basic framework of the mathematical model follows a model used in previous research. The initial susceptible population is assumed to be 30 million persons. Concerning the important parameters, such as the number of initial-exposure cases, R 0 (infectious power, or natural history) and, the starting day of intervention after the initial exposure, we checked the robustness of our conclusions by sensitivity analysis. We found that mass vaccination is preferable to ring vaccination when the values for the initial-exposure cases and R 0 are high and when the start of intervention by public health authorities is delayed. In the base-case situation, the mass vaccination strategy needs almost 30 million vaccine doses. On the other hand, though ring vaccination needs fewer doses, it needs fewer than 50â€‰000 doses in the worst-case scenario, that with larger first exposure, higher R 0, or later start of public health authority intervention. This mathematical model can measure the prevalence of an infectious disease and can evaluate control measures for it before an outbreak. Especially, it is useful for the planning of the outbreaks of emerging diseases such as severe acute respiratory syndrome (SARS) or for bioterrorism attacks involving such diseases as smallpox. In further research, we will have to take into account the population people vaccinated of for smallpox, who account for about 70% of the total population in Japan.


title: Chapter 11 Pathology: The Clinical Description of Human Disease

text: Publisher Summary This chapter discusses the fundamental concepts, terminology, and practice of pathology as the discipline dedicated to the understanding of causes, mechanisms, and effects of diseases. It describes some key terms, definitions, and concepts, presents historical human approaches to diseases, and provides an overview of current diagnostic practice and a vision for new interface with applied molecular biology. Pathology refers to the specialty of medical science concerned with the cause, development, structural/functional changes, and natural history associated with diseases. Disease refers to a definable deviation from a normal phenotype (observable characteristics due to genome and environment), evident via patient complaints (symptoms), and/or the measurements of a careful observer (signs). The cause of the disease is referred to as its etiology. One disease entity can have more than one etiology, and one etiology can lead to more than one disease. Each disease entity develops through a series of mechanistic chemical and cellular steps. This stepwise process of disease development is referred to as its pathogenesis. Pathogenesis can refer to the changes in the structure or function of an organism at the gross/clinical level and the stepwise molecular abnormalities leading to changes in cellular and tissue function. The presentation of a disease to a clinician is in the form of a human patient with variably specific complaints (symptoms), to which the examining physicians can add diagnostic sensitivity and specificity by making observations (screening for signs of diseases).


Management of CLL patients early in the COVID‐19 pandemic: An international survey of CLL experts


title: COVID-19 Pandemic: Survey of future use of personal protective equipment in optometric practice

text: Abstract Purpose The aim of this project was to evaluate which personal protective equipment (PPE) eye care practitioners (ECP) will use during the next months and also what they will ask the patient to use in clinical practice. Methods A social-media survey was carried out, asking 257 optometrists and opticians in Germany, Austria and Switzerland (i) which PPE they intended to use in the future (after lockdown and before herd immunity and / or vaccine availability) and (ii) what they would ask the patient to do in terms of this. Results 75% of the ECPs planned on wearing masks during refractions and 69% when fitting contact lens. 62% of the ECPs also expected their patients to wear masks in these tasks. This number is higher than for distance tasks such as fitting frames. Around 90% of the ECPs would, in addition to hand washing, disinfect their hands and around 80% expected their patients to do so too. Less than one third of ECPs favoured wearing safety spectacles, gloves and / or protective facial shields. 73% planed on disinfecting frames after they would have been tried on by customers. Conclusions In summary, most ECPs planed on continuing to use higher standards of PPE. Those, who intended to wear masks themselves, would ask their patients to also do so, combined with hand disinfection.


Treating cancer patients in times of COVID-19 pandemic: A virtual women cancers multidisciplinary meeting experience


title: The Ebola Outbreak: Catalyzing a “Shift” in Global Health Governance?

text: BACKGROUND: As the 2014 Ebola virus disease outbreak (EVD) transitions to its post-endemic phase, its impact on the future of global public health, particularly the World Health Organization (WHO), is the subject of continued debate. Criticism of WHO’s performance grew louder in the outbreak’s wake, placing this international health UN-specialized agency in the difficult position of navigating a complex series of reform recommendations put forth by different stakeholders. Decisions on WHO governance reform and the broader role of the United Nations could very well shape the future landscape of 21st century global health and how the international community responds to health emergencies. DISCUSSION: In order to better understand the implications of the EVD outbreak on global health and infectious disease governance, this debate article critically examines a series of reports issued by four high-level commissions/panels convened to specifically assess WHO’s performance post-Ebola. Collectively, these recommendations add increasing complexity to the urgent need for WHO reform, a process that the agency must carry out in order to maintain its legitimacy. Proposals that garnered strong support included the formation of an independent WHO Centre for Emergency Preparedness and Response, the urgent need to increase WHO infectious disease funding and capacity, and establishing better operational and policy coordination between WHO, UN agencies, and other global health partners. The recommendations also raise more fundamental questions about restructuring the global health architecture, and whether the UN should play a more active role in global health governance. SUMMARY: Despite the need for a fully modernized WHO, reform proposals recently announced by WHO fail to achieve the “evolution” in global health governance needed in order to ensure that global society is adequately protected against the multifaceted and increasingly complex nature of modern public health emergencies. Instead, the lasting legacy of the EVD outbreak may be its foreshadowing of a governance “shift” in formal sharing of the complex responsibilities of global health, health security, outbreak response, and managing health emergencies to other international structures, most notably the United Nations. Only time will tell if the legacy of EVD will include a WHO that has the full support of the international community and is capable of leading human society in this brave new era of the globalization of infectious diseases.


Adapting protocols for the care of surgical patients during the COVID‐19 pandemic


2019-nCoV: Polite with children!


title: Mechanism of falcipain-2 inhibition by α,β-unsaturated benzo[1,4]diazepin-2-one methyl ester

text: Falcipain-2 (FP-2) is a papain-family cysteine protease of Plasmodium falciparum whose primary function is to degrade the host red cell hemoglobin, within the food vacuole, in order to provide free amino acids for parasite protein synthesis. Additionally it promotes host cell rupture by cleaving the skeletal proteins of the erythrocyte membrane. Therefore, the inhibition of FP-2 represents a promising target in the search of novel anti-malarial drugs. A potent FP-2 inhibitor, characterized by the presence in its structure of the 1,4-benzodiazepine scaffold and an α,β-unsaturated methyl ester moiety capable to react with the Cys42 thiol group located in the active site of FP-2, has been recently reported in literature. In order to study in depth the inhibition mechanism triggered by this interesting compound, we carried out, through ONIOM hybrid calculations, a computational investigation of the processes occurring when the inhibitor targets the enzyme and eventually leads to an irreversible covalent Michael adduct. Each step of the reaction mechanism has been accurately characterized and a detailed description of each possible intermediate and transition state along the pathway has been reported.


title: Characterization of the cysteine protease domain of Semliki Forest virus replicase protein nsP2 by in vitro mutagenesis

text: The function of Semliki Forest Virus nsP2 protease was investigated by site-directed mutagenesis. Mutations were introduced in its protease domain, Pro39, and the mutated proteins were expressed in Escherichia coli, purified and their activity in vitro was compared to that of the wild type Pro39. Mutations M781T, A662T and G577R, found in temperature-sensitive virus strains, rendered the enzyme temperature-sensitive in vitro as well. Five conserved residues were required for the proteolytic activity of Pro39. Changes affecting Cys(478), His(548), and Trp(549) resulted in complete inactivation of the enzyme, whereas the replacements N600D and N605D significantly impaired its activity. The importance of Trp(549) for the proteolytic cleavage specificity is discussed and a new structural motif involved in substrate recognition by cysteine proteases is proposed.


title: On the clinical psychologist's role in the time of COVID‐19, with particular reference to experience gained in pediatric oncology

text: OBJECTIVE: The COVID‐19 pandemic seems to be developing into a planetary‐scale mental health experiment, undermining the foundations of our being human, obliging us to keep physically apart from one another, and inducing us to see other people as a potential threat. METHODS: In the world of pediatric oncology, we have found ourselves up against new challenges. In this article, we discuss the difficulties found in conducting psychological support sessions while complying with physical distancing rules, as well as wearing protective face masks, and even gloves; or while using modern remote communication telecommunications. RESULTS: The classic reasons behind requests for psychological support have been compounded by other, novel problems, such as: fewer relational resources for families at home, less chance to socialize, hospital stays with only one parent, the suspension of all teaching and group activities on the ward, economic difficulties caused by the pandemic, the rising levels of family conflictuality and generalized anxiety. CONCLUSIONS: It is essential to find new solutions that can be promptly implemented, reconfiguring the way we humanize our hospital wards.


title: 2017 international meeting of the Global Virus Network

text: Abstract The Global Virus Network (GVN) was established in 2011 to strengthen research and responses to emerging viral causes of human disease and to prepare against new viral pandemics. There are now 40 GVN Centers of Excellence and 6 Affiliate laboratories in 24 countries. The 2017 meeting was held from September 25–27 in Melbourne, Australia, and was hosted by the Peter Doherty Institute for Infection and Immunity and the Institut Pasteur. This report highlights the recent accomplishments of GVN researchers in several important areas of medical virology, including the recent Zika epidemic, infections by human papillomavirus, influenza, HIV, hepatitis C, HTLV-1, and chikungunya viruses, and new and emerging viruses in the Australasia region. Plans for the 2018 meeting also are noted.


title: Erratum zu: SARS-CoV-2/COVID-19 und neuromuskuläre Erkrankungen: Bestandsaufnahme der DGN (Deutsche Gesellschaft für Neurologie) Kommission Motoneuron- und neuromuskuläre Erkrankungen

text: Erratum zu: DGNeurologie 2020 https://doi Die ursprünglich publizierte Online-Version des Beitrags ent-hielt einen fehlerhaften Interessenkonflikt Dies wurde im Ori-ginalbeitrag berichtigt Bitte beachten Sie die korrigierte Version Wir bitten, den Fehler zu entschuldigen Die Online-Version des Originalartikels ist unter https://doi org/10


title: The enlightenment from two cases of asymptomatic infection with SARS-CoV-2: is it safe after 14 days of isolation?

text: Abstract From 78 laboratory-confirmed cases, we found 2 asymptomatic infections. One patient was discharged within 14 days after treatment. Another patient was discharged 25 days after treatment, and his TR-PCR test was still positive on the 15th day. We found that there may be virus carriers in asymptomatic population with epidemiological contact history. After 14 days of isolation, asymptomatic infection may still carry the virus, which means the risk of transmission and present a new challenge to home isolation.


title: Chapter 11.6 Clays and Clay Minerals as Drugs

text: Publisher Summary This chapter discusses the applications of clays and clay materials as drugs. Clay minerals are efficient against several aggressors that cause major disorders of the gut. These beneficial effects of clay minerals (on the gastrointestinal mucosa) are associated with two mechanisms of action: (1) adsorption of the aggressors or their toxic secretions and (2) modification of the thickness and rheological properties of the adherent mucus, reinforcing the natural defenses of the gastrointestinal mucosa. At the surface of the gut, a mucus gel adheres to the epithelial cells of the mucosa. This adherent mucus is dynamic, being continuously secreted by the calceiform cells and regularly eroded by environmental aggressors present in the gut lumen. The mucus gel is largely composed of glycoprotein polymers, lipids, and proteins linked together by covalent bonds. It acts as a physical barrier protecting the mucosa against penetration by extraneous molecules and mechanical injury. By maintaining a pH gradient and competing with the epithelial surface for microorganisms, the mucus gel also acts as a chemical barrier.


Intramatricial methotrexate for treatment of resistant acrodermatitis continua of Hallopeau: an alterative in Covid‐19


title: Travel Medicine Online International sources of travel medicine information on the Internet

text: Abstract Access to global information through the Internet has become an essential ingredient to successful practice in travel medicine. Internet sites that may be useful to travel health practitioners include those that represent international organisations (eg. http://www.who.int), national and international professional bodies (eg. http://www.istm.org), national public health and disease control centres (eg. http://www.cdc.gov). These useful sites often include online journals, geographic epidemiological information, regular outbreak alerts and news and downloadable information sheets for travellers, as well as those providing official guidelines and policies in travel medicine. It is also useful to have access to search engines, which can search the literature as well as the Internet.


title: Cell‐Based Hepatitis C Virus Infection Fluorescence Resonance Energy Transfer (FRET) Assay for Antiviral Compound Screening

text: Hepatitis C virus (HCV) affects an estimated 3% of the population and is a leading cause of chronic liver disease worldwide. Since HCV therapeutic and preventative options are limited, the development of new HCV antivirals has become a global health care concern. This has spurred the development of cell‐based infectious HCV high‐throughput screening assays to test the ability of compounds to inhibit HCV infection. This unit describes methods that may be used to assess the in vitro efficacy of HCV antivirals using a cell‐based high‐throughput fluorescence resonance energy transfer (FRET) HCV infection screening assay, which allows for the identification of inhibitors that target HCV at any step in the viral life cycle. Basic protocols are provided for compound screening during HCV infection and analysis of compound efficacy using an HCV FRET assay. Support protocols are provided for propagation of infectious HCV and measurement of viral infectivity. Curr. Protoc. Microbiol. 18:17.5.1‐17.5.27. © 2010 by John Wiley & Sons, Inc.


title: Extending and adapting the concept of quality management for museums and cultural heritage attractions: A comparative study of southern European cultural heritage managers' perceptions

text: Quality in cultural heritage attractions is mainly approached from the visitors' satisfaction perspective, and the literature does not contain a clear definition of quality in the management of cultural heritage sites open to the public. The present study aims to reframe this trend. By way of theoretical contribution, we propose a definition of quality in cultural heritage attractions management based on dimensions such as the capacity of preserving the cultural assets, the ability to communicate effectively their significance, the quality of commodification for visitor use, and the ability to boost intercultural competence and promote intercultural dialogue. Based on the above, an empirical, qualitative study was conducted on the cultural heritage managers' current perceptions of quality. The results suggest that a profound asymmetry exists among practitioners' opinions and practices, and four types of cultural heritage managers were defined with regard to their perception of quality: Reactionary, Reticent, Pragmatic, Enthusiastic.


title: COVID-19-Pandemie: strukturierte Erweiterung von Beatmungskapazitäten mithilfe von Heimrespiratoren

text: Due to the current COVID-19 pandemic there is a need for a rapid increase in intensive care and ventilation capacities. Delivery times for additional intensive care respirators are currently not foreseeable. An option to increase ventilation capacities not only for COVID-19, but for all patients requiring mechanical ventilation is to use home respirators. Home respirators are turbine respirators, so they can usually be operated without high-pressure oxygen connections and can therefore also be used in areas outside the classical intensive care medical infrastructure. Due to their limited technical features, home respirators are not suitable for the treatment of severely affected patients but can be used for weaning after respiratory improvement, which means that intensive care respirators are available again more quickly. Respiratory therapists are specially trained nurses or therapists in the field of out of hospital ventilation and can independently use home ventilation respirators, for example for weaning in the intensive care unit. Thus, they relieve intensive care nursing staff in the pandemic. Due to the COVID-19 pandemic medical students from the Oldenburg University are currently being trained in operating home respirators to provide basic support in the hospital if necessary.


title: What are the key success factors for strategy formulation and implementation? Perspectives of managers in the hotel industry

text: This study investigates how hotel managers describe strategy and identify key success factors for its formulation and implementation. The study analyzes qualitative data collected through semi-structured interviews with property level top managers of hotels in Hong Kong. The findings show that hotel managers prioritize competition analysis and macro-environmental conditions over internal characteristics such as teamwork in strategy formulation. In the implementation phase, however, internal considerations such as employee involvement and strategic consensus are given prominence. This study provides a significant contribution by examining how top level practitioners in the industry interpret success factors in their strategic management efforts, and it highlights a largely neglected area in the hospitality and tourism management literature.


Comments on: The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality


title: Viral Inclusion Bodies in Tracheobronchial Epithelium of Asymptomatic Subjects

text: During a survey conducted for the cytodiagnosis of early bronchogenic carcinoma, cytoplasmic viral inclusion bodies were found sporadically in tracheobronchial smears of asymtomatic patients of both sexes (ages ranging from 18 to 80 years) undergoing general endotracheal anesthesia for surgery. A review of 3,049 cases performed to assess the frequency of occurrence of this phenomenon showed a 1.1 percent incidence in all smears studied. There was no relationship between smoking habit, age, or sex and the presence of inclusion bodies; however, there was a marked seasonal incidence, with 60 percent of inclusion-bearing smears being found during the months of January through March.


title: Molecular and cellular evidence of natural Venezuelan equine encephalitis virus infection in frugivorous bats in Colombia

text: BACKGROUND AND AIM: Venezuelan equine encephalitis virus (VEEV) is an alphavirus that causes encephalitis with a high impact on public health in Latin America. However, only in Guatemala, Trinidad and Tobago, and Mexico have found antibodies in VEEV in bats, using immunohistochemistry, the sensitivity and specificity are improved; thus, it is better for demonstrating natural infection in bats as potential hosts. This study aimed to determine the presence of VEEV in tissues of frugivorous bats. MATERIALS AND METHODS: A prospective descriptive cross-sectional study with a non-probabilistic sampling was carried out in 12 localities of Córdoba and Sucre area of the Colombian Caribbean. Two hundred and eighty-six bats were captured using fog nets, and the specimens according to taxonomic keys were classified. According to the Ethics Committee of the University of Córdoba, the bats were treated with analgesics and anesthetics. Blood samples were taken and then euthanized to obtain tissues and organs which were preserved in liquid N2 at −196°C. A portion of each organ was fixed in 10% buffered formalin for the detection of antigens by immunohistochemistry. Several pathological anatomy analyses were performed to determine the histological characteristics of tissue lesions of frugivorous bats naturally infected with the VEEV. RESULTS: Of the 286 bats captured, 23 species were identified. In samples of the brain, spleen, and lung of two frugivorous bats (2/286=0.70%) Artibeus planirostris and Sturnira lilium, the presence of VEEV was confirmed by immunohistochemistry. CONCLUSION: A fragment of the nsP4 non-structural protein gene corresponding to the alphavirus was amplified. Two samples were positive (2/286=0.70%) in frugivorous bats; A. planirostris (code GenBank: MG820274) and S. lilium (code GenBank: MG820275). The present study showed the first molecular evidence and cellular evidence (histopathology and immunohistochemistry) of natural VEEV infection in frugivorous bats in Colombia; these bats could be a host of this zoonosis.


title: Serine-scanning mutagenesis studies of the C-terminal heptad repeats in the SARS coronavirus S glycoprotein highlight the important role of the short helical region

text: Abstract The fusion subunit of the SARS-CoV S glycoprotein contains two regions of hydrophobic heptad-repeat amino acid sequences that have been shown in biophysical studies to form a six-helix bundle structure typical of the fusion-active core found in Class I viral fusion proteins. Here, we have applied serine-scanning mutagenesis to the C-terminal-most heptad-repeat region in the SARS-CoV S glycoprotein to investigate the functional role of this region in membrane fusion. We show that hydrophobic sidechains at a and d positions only within the short helical segment of the C-terminal heptad-repeat region (I1161, I1165, L1168, A1172, and L1175) are critical for cell–cell fusion. Serine mutations at outlying heptad-repeat residues that form an extended chain in the core structure (V1158, L1179, and L1182) do not affect fusogenicity. Our study provides genetic evidence for the important role of α-helical packing in promoting S glycoprotein-mediated membrane fusion.


title: Development of a homogeneous time-resolved fluorescence assay for detection of viral double-stranded RNA

text: Abstract The group of positive-sense single-stranded RNA ((+) ssRNA) viruses includes many important human pathogens. However, specific antiviral agents are not currently available for many RNA viruses. For screening of antiviral agents, methods that are simple, rapid, and compatible with high-throughput are required. Here, we describe a novel method for measurement of double-stranded RNA using a homogeneous time-resolved fluorescence assay. This method allowed detection of human rhinovirus (HRV), enterovirus, coxsackievirus, and murine norovirus. Furthermore, this method detected antiviral activity of a HRV 3C protease inhibitor. The assay may be useful for discovery of antiviral agents against (+) ssRNA viruses.


title: Inhibitory effect of silver nanomaterials on transmissible virus-induced host cell infections

text: Abstract Coronaviruses belong to the family Coronaviridae, which primarily cause infection of the upper respiratory and gastrointestinal tract of hosts. Transmissible gastroenteritis virus (TGEV) is an economically significant coronavirus that can cause severe diarrhea in pigs. Silver nanomaterials (Ag NMs) have attracted great interests in recent years due to their excellent anti-microorganism properties. Herein, four representative Ag NMs including spherical Ag nanoparticles (Ag NPs, NM-300), two kinds of silver nanowires (XFJ011) and silver colloids (XFJ04) were selected to study their inhibitory effect on TGEV-induced host cell infection in vitro. Ag NPs were uniformly distributed, with particle sizes less than 20 nm by characterization of environmental scanning electron microscope and transmission electron microscope. Two types of silver nanowires were 60 nm and 400 nm in diameter, respectively. The average diameter of the silver colloids was approximately 10 nm. TGEV infection induced the occurring of apoptosis in swine testicle (ST) cells, down-regulated the expression of Bcl-2, up-regulated the expression of Bax, altered mitochondrial membrane potential, activated p38 MAPK signal pathway, and increased expression of p53 as evidenced by immunofluorescence assays, real-time PCR, flow cytometry and Western blot. Under non-toxic concentrations, Ag NPs and silver nanowires significantly diminished the infectivity of TGEV in ST cells. Moreover, further results showed that Ag NPs and silver nanowires decreased the number of apoptotic cells induced by TGEV through regulating p38/mitochondria-caspase-3 signaling pathway. Our data indicate that Ag NMs are effective in prevention of TGEV-mediated cell infection as a virucidal agent or as an inhibitor of viral entry and the present findings may provide new insights into antiviral therapy of coronaviruses.


title: Chapter 5 Clinical Applications of Quantitative Real-Time PCR in Virology

text: Abstract Since the invention of the polymerase chain reaction (PCR) and discovery of Taq polymerase, PCR has become a staple in both research and clinical molecular laboratories. As clinical and diagnostic needs have evolved over the last few decades, demanding greater levels of sensitivity and accuracy, so too has PCR performance. Through optimisation, the present-day uses of real-time PCR and quantitative real-time PCR are enumerable. The technique, combined with adoption of automated processes and reduced sample volume requirements, makes it an ideal method in a broad range of clinical applications, especially in virology. Complementing serologic testing by detecting infections within the pre-seroconversion window period and infections with immunovariant viruses, real-time PCR provides a highly valuable tool for screening, diagnosing, or monitoring diseases, as well as evaluating medical and therapeutic decision points that allows for more timely predictions of therapeutic failures than traditional methods and, lastly, assessing cure rates following targeted therapies. All of these serve vital roles in the continuum of care to enhance patient management. Beyond this, quantitative real-time PCR facilitates advancements in the quality of diagnostics by driving consensus management guidelines following standardisation to improve patient outcomes, pushing for disease eradication with assays offering progressively lower limits of detection, and rapidly meeting medical needs in cases of emerging epidemic crises involving new pathogens that may result in significant health threats.


title: Integration of Global Analyses of Host Molecular Responses with Clinical Data To Evaluate Pathogenesis and Advance Therapies for Emerging and Re-emerging Viral Infections

text: [Image: see text] Outbreaks associated with emerging and re-emerging viral pathogens continue to increase in frequency and are associated with an increasing burden to global health. In light of this, there is a need to integrate basic and clinical research for investigating the connections between molecular and clinical pathogenesis and for therapeutic development strategies. Here, we will discuss this approach with a focus on the emerging viral pathogens Middle East respiratory syndrome coronavirus (MERS-CoV), Ebola virus (EBOV), and monkeypox virus (MPXV) from the context of clinical presentation, immunological and molecular features of the diseases, and OMICS-based analyses of pathogenesis. Furthermore, we will highlight the role of global investigations of host kinases, the kinome, for investigating emerging and re-emerging viral pathogens from the context of characterizing cellular responses and identifying novel therapeutic targets. Lastly, we will address how increased integration of clinical and basic research will assist treatment and prevention efforts for emerging pathogens.


Clonal T-cell cross-reactivity between myelin antigens MBP and PLP and human respiratory coronaviruses in multiple sclerosis


title: Mortality impacts of the coronavirus disease (COVID-19) outbreak by sex and age: rapid mortality surveillance system, Italy, 1 February to 18 April 2020

text: Data from the rapid mortality surveillance system in 19 major Italian cities were used to carry out a timely assessment of the health impact of the COVID-19 epidemic. By 18 April, a + 45% excess in mortality was observed, with a higher impact in the north of the country (+ 76%). The excess was greatest among men, with an increasing trend by age. Surveillance data can be used to evaluate the lockdown and re-opening phases.


title: The efficacy of medical masks and respirators against respiratory infection in healthcare workers

text: OBJECTIVE: We aimed to examine the efficacy of medical masks and respirators in protecting against respiratory infections using pooled data from two homogenous randomised control clinical trials (RCTs). METHODS: The data collected on 3591 subjects in two similar RCTs conducted in Beijing, China, which examined the same infection outcomes, were pooled. Four interventions were compared: (i) continuous N95 respirator use, (ii) targeted N95 respirator use, (iii) medical mask use and (iv) control arm. The outcomes were laboratory‐confirmed viral respiratory infection, influenza A or B, laboratory‐confirmed bacterial colonisation and pathogens grouped by mode of transmission. RESULTS: Rates of all outcomes were consistently lower in the continuous N95 and/or targeted N95 arms. In adjusted analysis, rates of laboratory‐confirmed bacterial colonisation (RR 0.33, 95% CI 0.21‐0.51), laboratory‐confirmed viral infections (RR 0.46, 95% CI 0.23‐0.91) and droplet‐transmitted infections (RR 0.26, 95% CI 0.16‐0.42) were significantly lower in the continuous N95 arm. Laboratory‐confirmed influenza was also lowest in the continuous N95 arm (RR 0.34, 95% CI 0.10‐1.11), but the difference was not statistically significant. Rates of laboratory‐confirmed bacterial colonisation (RR 0.54, 95% CI 0.33‐0.87) and droplet‐transmitted infections (RR 0.43, 95% CI 0.25‐0.72) were also lower in the targeted N95 arm, but not in medical mask arm. CONCLUSION: The results suggest that the classification of infections into droplet versus airborne transmission is an oversimplification. Most guidelines recommend masks for infections spread by droplets. N95 respirators, as “airborne precautions,” provide superior protection for droplet‐transmitted infections. To ensure the occupational health and safety of healthcare worker, the superiority of respirators in preventing respiratory infections should be reflected in infection control guidelines.


The Lung Tissue Microbiota Features of 20 Deceased Patients with COVID-19


title: Biochemical characterisation of lectin from Indian hyacinth plant bulbs with potential inhibitory action against human cancer cells

text: Abstract This work describes purification and characterisation of a monocot mannose-specific lectin from Hyacinth bulbs. The purified lectin has a molecular mass of ∼30kDa in reducing as well as in non-reducing SDS-PAGE. In hydrodynamic studies by Dynamic Light Scattering (DLS) showed that purified lectin was monomeric in nature with a molecular size of 2.38±0.03nm. Agglutination activity of purified lectin was confirmed by rabbit erythrocytes and its agglutination activity was inhibited by d-mannose and a glycoprotein (ovalbumin). Glycoprotein nature of purified lectin was confirmed by Periodic Acid Schiff’s (PAS) stain. Purified lectin showed moderate pH and thermal stability by retaining hemagglutination activity from pH 6–8 and temperature up to 60°C. It also suppressed the growth of human colon cancer cells (Caco-2) and cervical cancer cells (HeLa) with IC50 values of 127μg/mL and 158μg/mL respectively, after 24-h treatment. Morphological studies of treated cells (Caco-2 and HeLa) with hyacinth lectin by AO/EB dual staining indicated that purified lectin is capable of inducing apoptosis.


title: Two enzyme immunoassays for the detection of antibody to rodent coronaviruses

text: Abstract Two enzyme immunoassays for detection of antibody to rodent coronaviruses were compared. Mouse hepatitis virus (MHV), strain JHM, antigen was in the form of formalin-fixed, infected 17 C1 1 cells. This antigen detected antibody to the homologous strain of MHV as well as to two heterologous MHV strains and a serologically related rat coronavirus, sialodacryodenititis virus. Antibody titers in assays using horseradish peroxidase (HRP)-conjugated or ureiase-conjugated anti-mouse IgG were substantially higher than in an indirect immunofluorescence assay. The ureiase assay was somewhat more sensitive than the HRP assay. MHV-JHM antigen was stable under a variety of storage conditions for at least two months.


title: Klassevirus 1, a previously undescribed member of the family Picornaviridae, is globally widespread

text: BACKGROUND: Diarrhea is the third leading infectious cause of death worldwide and is estimated to be responsible for approximately 2 million deaths a year. While many infectious causes of diarrhea have been established, approximately 40% of all diarrhea cases are of unknown etiology. In an effort to identify novel viruses that may be causal agents of diarrhea, we used high throughput mass sequencing to analyze stool samples collected from patients with acute diarrhea. RESULTS: Sequences with limited similarity to known picornaviruses were detected in a stool sample collected in Australia from a child with acute diarrhea. Using a combination of mass sequencing, RT-PCR, 5' RACE and 3' RACE, a 6383 bp fragment of the viral genome was sequenced. Phylogenetic analysis demonstrated that this virus was highly divergent from, but most closely related to, members of the genus Kobuvirus. We have tentatively named this novel virus klassevirus 1. We also detected klassevirus 1 by RT-PCR in a diarrhea specimen collected from a patient in St. Louis, United States as well as in untreated sewage collected in Barcelona, Spain. CONCLUSION: Klassevirus 1 is a previously undescribed picornavirus that is globally widespread and present on at least three continents. Further investigations to determine whether klassevirus 1 is a human pathogen are needed.


Preventing COVID-19 and Its Sequela: “There Is No Magic Bullet . . . It's Just Behaviors”


title: Cleavage of spike protein of SARS coronavirus by protease factor Xa is associated with viral infectivity

text: The spike (S) protein of SARS coronavirus (SARS-CoV) has been known to recognize and bind to host receptors, whose conformational changes then facilitates fusion between the viral envelope and host cell membrane, leading to viral entry into target cells. However, other functions of SARS-CoV S protein such as proteolytic cleavage and its implications to viral infection are incompletely understood. In this study, we demonstrated that the infection of SARS-CoV and a pseudovirus bearing the S protein of SARS-CoV was inhibited by a protease inhibitor Ben-HCl. Also, the protease Factor Xa, a target of Ben-HCl abundantly expressed in infected cells, was able to cleave the recombinant and pseudoviral S protein into S1 and S2 subunits, and the cleavage was inhibited by Ben-HCl. Furthermore, this cleavage correlated with the infectivity of the pseudovirus. Taken together, our study suggests a plausible mechanism by which SARS-CoV cleaves its S protein to facilitate viral infection.


title: Organ-specific features of natural killer cells

text: Natural killer (NK) cells can be swiftly mobilized by danger signals and are among the earliest arrivals at target organs of disease. However, the role of NK cells in mounting inflammatory responses is often complex and sometimes paradoxical. Here, we examine the divergent phenotypic and functional features of NK cells, as deduced largely from experimental mouse models of pathophysiological responses in the liver, mucosal tissues, uterus, pancreas, joints and brain. Moreover, we discuss how organ-specific factors, the local microenvironment and unique cellular interactions may influence the organ-specific properties of NK cells.


title: Complete genomic sequence analysis of infectious bronchitis virus Ark DPI strain and its evolution by recombination

text: An infectious bronchitis virus Arkansas DPI (Ark DPI) virulent strain was sequenced, analyzed and compared with many different IBV strains and coronaviruses. The genome of Ark DPI consists of 27,620 nucleotides, excluding poly (A) tail, and comprises ten open reading frames. Comparative sequence analysis of Ark DPI with other IBV strains shows striking similarity to the Conn, Gray, JMK, and Ark 99, which were circulating during that time period. Furthermore, comparison of the Ark genome with other coronaviruses demonstrates a close relationship to turkey coronavirus. Among non-structural genes, the 5'untranslated region (UTR), 3C-like proteinase (3CL(pro)) and the polymerase (RdRp) sequences are 100% identical to the Gray strain. Among structural genes, S1 has 97% identity with Ark 99; S2 has 100% identity with JMK and 96% to Conn; 3b 99%, and 3C to N is 100% identical to Conn strain. Possible recombination sites were found at the intergenic region of spike gene, 3'end of S1 and 3a gene. Independent recombination events may have occurred in the entire genome of Ark DPI, involving four different IBV strains, suggesting that genomic RNA recombination may occur in any part of the genome at number of sites. Hence, we speculate that the Ark DPI strain originated from the Conn strain, but diverged and evolved independently by point mutations and recombination between field strains.


title: Structural elucidation of SARS-CoV-2 vital proteins: Computational methods reveal potential drug candidates against main protease, Nsp12 polymerase and Nsp13 helicase

text: Abstract The recently emerged SARS-CoV-2 caused a major outbreak of coronavirus disease 2019 (COVID-19) and instigated a widespread fear, threatening global health security. To date, no licensed antiviral drugs or vaccines are available against COVID-19 although several clinical trials are underway to test possible therapies. During this urgency situation, computational drug discovery methods provide an alternative to tiresome high-throughput screening, particularly in the hit-to-lead-optimization stage. Identification of small molecules that specifically target viral replication apparatus has indicated highest potential towards antiviral drug discovery. In this work, we present potential compounds that specifically target SARS-CoV-2 vital proteins, including the main protease, Nsp12 RNA polymerase and Nsp13 helicase. An integrative virtual screening and molecular dynamics simulations approach led to the identification of potential binding modes and favourable molecular interaction profile of corresponding compounds. Moreover, the identification of structurally important binding site residues in conserved motifs located inside the active site highlights relative importance of ligand binding based on residual energy decomposition analysis. Although the current study lacks experimental validation, the structural information obtained from this computational study has paved way for the design of targeted inhibitors to combat COVID-19 outbreak.


title: The Usefulness of Platelet-derived Microparticle as Biomarker of Antiplatelet Therapy in Kawasaki Disease

text: Little is known about platelet dynamics and the effect of antiplatelet therapy in Kawasaki disease (KD). This study sought to define platelet activation dynamics in KD patients by assaying platelet-derived microparticles (PDMPs). We measured plasma PDMPs levels in 46 patients with KD using an enzyme-linked immunosorbent assay (ELISA). Blood samples were collected before, at 2–5 days, and 9–15 days after intravenous immunoglobulin (IVIG) infusion, 2 months and 4–5 months after the onset of KD. We measured PDMP levels in 23 febrile and 10 afebrile control patients. In the acute phase of KD patients, PDMP levels increased significantly after IVIG treatment (12.04 ± 5.58 nmol before IVIG infusion vs. 19.81 ± 13.21 nmol at 2–5 days after IVIG infusion, P = 0.006). PDMP levels were negatively correlated with age and positively correlated with procalcitonin levels in the acute phase of KD. No significant difference was found in PDMP levels between KD patients with and without coronary artery lesion (CAL). Elevated PDMP levels after IVIG therapy significantly decreased below the pre-IVIG level in subacute phase (19.81 ± 13.21 nmol at 2–5 days after IVIG infusion vs. 8.33 ± 2.02 nmol at 9–15 days after IVIG infusion, P < 0.001), and PDMP levels stayed below the pre-IVIG level in the convalescent phase, during which antiplatelet therapy was given. However, PDMP levels rebounded after discontinuing aspirin in 17 patients. In conclusion, enhanced platelet activation was noted before treatment of KD and peaked immediately after IVIG treatment. Recurrent rising of PDMP levels was observed after discontinuing aspirin, although there were no significant differences between the PDMP levels at 2 months after the onset of KD and those at 4–5 months after the onset of the disease.


title: Calf-level risk factors for neonatal diarrhea and shedding of Cryptosporidium parvum in Ontario dairy calves

text: Abstract This work was conducted to investigate calf-level factors that influence the risk of neonatal diarrhea and shedding of Cryptosporidium parvum oocysts in calves, on dairy farms in Ontario with histories of calf diarrhea or cryptosporidiosis. Fecal samples were collected weekly for 4 weeks from each of 1045 calves under 30 days of age on 11 dairy farms in south-western Ontario during the summer of 2003 and the winter of 2004. A questionnaire designed to gather information on calf-level management factors was administered on farm for each calf in the study. Samples were examined for C. parvum oocysts by microscopy, and a subset of specimens was also tested for enterotoxigenic Escherichia coli, Salmonella, bovine rotavirus and bovine coronavirus. The consistency of each sample was scored and recorded at the time of collection in order to assess the presence or absence of diarrhea. In addition, a blood sample was taken from each calf upon enrolment in the study, for assessment of maternal antibody transfer and for polymerase chain reaction testing for persistent bovine viral diarrhea virus infection. Using the GLLAMM function in Stata 9.0, multilevel regression techniques were employed to investigate associations between management practices and the risk of C. parvum shedding or diarrhea. C. parvum oocysts were detected in the feces of 78% of the 919 calves from which all four fecal samples had been collected. Furthermore, 73% of the 846 calves for which all four fecal consistency scores had been recorded were diarrheic at the time of collection of at least one sample. Significant predictors of the calf-level risk of C. parvum shedding included the use of calf diarrhea prophylaxis in pregnant cows, and the type of maternity facilities in which the calves were born. Factors associated with an increased risk of diarrhea were leaving the calf with the dam for more than an hour after birth, and the birth of a calf in the summer as opposed to winter. Calves shedding C. parvum oocysts had 5.3 (95% CI 4.4, 6.4) times the odds of diarrhea than non-shedding calves, controlling for other factors included in the final multivariable model. Furthermore, infected calves shedding more than 2.2×105 oocysts per gram of feces were more likely to scour than infected calves shedding lower numbers of oocysts (OR=6.1, 95% CI 4.8, 7.8). The odds of diarrhea in calves shedding oocysts that had been allowed to remain with their dams for more than an hour were higher than the odds of diarrhea in shedding calves that had been separated from their dams within an hour after birth.