title: Tubuloreticular Inclusions in the Absence of Systemic Lupus Erythematosus and HIV Infection: A Report of Three Pediatric Cases

text: Tubuloreticular inclusions (TRIs) are subcellular structures located within the cisternae of endoplasmic reticulum. Formation of TRIs has been linked to the exposure of excess interferon (IFN), either from endogenous or exogenous sources. In renal disease, TRIs have been most commonly associated with systemic lupus erythematosus (SLE), and human immunodeficiency virus-associated nephropathy (HIVAN). Case reports of patients with renal biopsies showing TRIs without underlying SLE or HIV are infrequent in adults, and to our knowledge none have been reported in children. We report 3 pediatric cases in which the renal biopsy showed TRIs on electron microscopy without underlying SLE or HIV infection. The first patient presented at 2 years of age with nephrotic syndrome and renal failure. His renal biopsy revealed focal segmental glomerulosclerosis and TRIs. The second patient presented at 6 months of age with infantile nephrotic syndrome, and his renal biopsy revealed membranous glomerulopathy and TRIs. The last patient presented at 4 years of age with acute kidney injury of unclear etiology leading to chronic kidney disease. Her biopsy revealed acute and chronic tubulointerstitial nephritis with TRIs. Despite extensive evaluation in all 3 patients, including testing for HIV infection and SLE, we could not identify an underlying etiology to explain the presence of TRIs. In conclusion, renal biopsy with TRIs in the absence of underling SLE and HIV remains obscure. We propose a possible role for excess IFN triggered by an abnormal immune response to common viral infections in the formation of TRIs and renal injury.


title: Cytokines and acute phase proteins associated with acute swine influenza infection in pigs

text: Abstract This study set out to investigate the cytokines and acute phase proteins (APPs) associated with the acute stages of experimentally-induced swine influenza virus (SIV) infection in 3-week-old, colostrum-deprived, caesarean-derived piglets. The piglets were inoculated intratracheally with 107.5 50% egg infective dose [EID50] Swine/Belgium/1/98 (H1N1) SIV and were euthanased at time-points between 0 and 120h post-inoculation (PI). Broncho-alveolar lavage fluid (BALF), lung homogenates and sera were examined for inflammatory mediators by bioassay or ELISA. Interferon (IFN)-α, interleukin (IL)-6, IL-1 and tumour necrosis factor (TNF)-α peaked in BALF 24–30h PI, when virus titres and the severity of clinical signs were maximal. Whereas IFN-γ and IL-12, but not IL-18, increased in tandem in BALF, serum cytokine concentrations were either undetectable or were up to 100-fold lower. The APP C-reactive protein (CRP) and haptoglobin peaked 24h later than the cytokines and reached higher levels in serum than in BALF. In contrast, lipopolysaccharide (LPS)-binding protein (LBP) only increased in BALF. Lung virus titres tightly correlated with BALF IFN-α, IL-6, IL-1, TNF-α, IFN-γ and IL-12, as well as with serum IL-6, IFN-α and IFN-γ. Signs of disease correlated with the same cytokines in BALF and serum, as well as with BALF LBP and serum CRP. The findings suggest that IFN-γ and IL-12 play a role in the pathogenesis of SIV and that APPs are induced by cytokines. This influenza infection model may have value in assessing the therapeutic potential of cytokine antagonists.


title: COVID-19: Specific and non-specific clinical manifestations and symptoms: The current state of knowledge

text: Coronavirus disease 2019 (COVID-19), due to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become an epidemiological threat and a worldwide concern. SARS-CoV-2 has spread to 210 countries worldwide and more than 6,500,000 confirmed cases and 384,643 deaths have been reported, while the number of both confirmed and fatal cases is continually increasing. COVID-19 is a viral disease that can affect every age group—from infants to the elderly—resulting in a wide spectrum of various clinical manifestations. COVID-19 might present different degrees of severity—from mild or even asymptomatic carriers, even to fatal cases. The most common complications include pneumonia and acute respiratory distress syndrome. Fever, dry cough, muscle weakness, and chest pain are the most prevalent and typical symptoms of COVID-19. However, patients might also present atypical symptoms that can occur alone, which might indicate the possible SARS-CoV-2 infection. The aim of this paper is to review and summarize all of the findings regarding clinical manifestations of COVID-19 patients, which include respiratory, neurological, olfactory and gustatory, gastrointestinal, ophthalmic, dermatological, cardiac, and rheumatologic manifestations, as well as specific symptoms in pediatric patients.


title: A simple procedure for the derivation of electron density based surfaces of drug-receptor complexes from a combination of X-ray data and theoretical calculations

text: Abstract To contribute to an understanding of biological recognition and interaction, an easy-to-use procedure was developed to generate and display molecular surfaces and selected electron density based surface properties. To overcome the present limitations to derive electron densities of macromolecules, the considered systems were reduced to appropriate substructures around the active centers. The combination of experimental X-ray structural information and aspherical atomic electron density data from theoretical calculations resulted in properties like the electrostatic potential and the Hirshfeld surface which allowed a study of electronic complementarity and the identification of sites and strengths of drug-receptor interactions. Applications were examined for three examples. The anilinoquinazoline gefitinib (Iressa®) belongs to a new class of anticancer drugs that inhibit the tyrosine kinase activity of the epidermal growth factor receptor (EGFR). In the second example, the interaction of epoxide inhibitors with the main protease of the SARS coronavirus was investigated. Furthermore, the progesterone receptor complex was examined. The quantitative analysis of hydrogen bonding in the chosen substructure systems follows a progression elaborated earlier on the basis of accurate small molecule crystal structures. This finding and results from modified substructures suggest that also the surface properties seem robust enough to provide stable information about the recognition of interacting biomolecular species although they are obtained from medium molecular weighted subfragments of macromolecular complexes, which consist of no more than ∼40 residues.


Schmallenberg virus: Responding to the challenge


title: Prevalence of respiratory viruses and antiviral MxA responses in children with febrile urinary tract infection

text: Blood myxovirus resistance protein A (MxA) has broad antiviral activity, and it is a potential biomarker for symptomatic virus infections. Limited data is available of MxA in coinciding viral and bacterial infections. We investigated blood MxA levels in children hospitalized with a febrile urinary tract infection (UTI) with or without simultaneous respiratory virus infection. We conducted a prospective observational study of 43 children hospitalized with febrile UTI. Nasopharyngeal swab samples were collected at admission and tested for 16 respiratory viruses by nucleic acid detection methods. Respiratory symptoms were recorded, and blood MxA levels were determined. The median age of study children was 4 months (interquartile range, 2–14 months). A respiratory virus was detected in 17 (40%) children with febrile UTI. Of the virus-positive children with febrile UTI, 7 (41%) had simultaneous respiratory symptoms. Blood MxA levels were higher in virus-positive children with respiratory symptoms (median, 778 [interquartile range, 535–2538] μg/L) compared to either virus-negative (155 [94–301] μg/L, P < 0.001) or virus-positive (171 [112–331] μg/L, P = 0.006) children without respiratory symptoms at presentation with febrile UTI. MxA differentiated virus-positive children with respiratory symptoms from virus-negative without symptoms by an area under the receiver operating characteristic curve of 0.96. Respiratory viruses were frequently detected in children with febrile UTI. In UTI with simultaneous respiratory symptoms, host antiviral immune response was demonstrated by elevated blood MxA protein levels. MxA protein could be a robust biomarker of symptomatic viral infection in children with febrile UTI.


title: Expanding the Use of Noninvasive Ventilation During an Epidemic

text: Noninvasive ventilation (NIV) is a proved and effective therapeutic option for some patients with respiratory failure. During an epidemic, NIV can free up respirators and other intensive care unit equipment for patients with respiratory insufficiency whose survival depends exclusively on invasive ventilation. Some guidelines have indicated that NIV is potentially hazardous and should not be recommended for use during epidemics, given the perceived potential risk of transmission from aerosolized pathogen dispersion to other patients or medical staff. Conversely, some reports of previous epidemics describe NIV as a very efficient and safe modality of respiratory support, if strict infection control measures are implemented. We discuss NIV use during epidemics and indicate the need for prospective randomized clinical studies on the efficacy of NIV in epidemic conditions to provide important information to the current body of literature. Meanwhile, the use of NIV under strict infection control guidelines should be incorporated into epidemic preparedness planning. (Disaster Med Public Health Preparedness. 2014;8:1-5)


title: Using thermodynamic parameters to calibrate a mechanistic dose-response for infection of a host by a virus

text: Abstract Assessing the risk of infection from emerging viruses or of existing viruses jumping the species barrier into novel hosts is limited by the lack of dose response data. The initial stages of the infection of a host by a virus involve a series of specific contact interactions between molecules in the host and on the virus surface. The strength of the interaction is quantified in the literature by the dissociation constant (Kd) which is determined experimentally and is specific for a given virus molecule/host molecule combination. Here, two stages of the initial infection process of host intestinal cells are modelled, namely escape of the virus in the oral challenge dose from the innate host defenses (e.g. mucin proteins in mucus) and the subsequent binding of any surviving virus to receptor molecules on the surface of the host epithelial cells. The strength of virus binding to host cells and to mucins may be quantified by the association constants, Ka and Kmucin, respectively. Here, a mechanistic dose-response model for the probability of infection of a host by a given virus dose is constructed using Ka and Kmucin which may be derived from published Kd values taking into account the number of specific molecular interactions. It is shown that the effectiveness of the mucus barrier is determined not only by the amount of mucin but also by the magnitude of Kmucin. At very high Kmucin values, slight excesses of mucin over virus are sufficient to remove all the virus according to the model. At lower Kmucin values, high numbers of virus may escape even with large excesses of mucin. The output from the mechanistic model is the probability (p1) of infection by a single virion which is the parameter used in conventional dose-response models to predict the risk of infection of the host from the ingested dose. It is shown here how differences in Ka (due to molecular differences in an emerging virus strain or new host) affect p1, and how these differences in Ka may be quantified in terms of two thermodynamic parameters, namely enthalpy and entropy. This provides the theoretical link between sequencing data and risk of infection. Lack of data on entropy is a limitation at present and may also affect our interpretation of Kd in terms of infectivity. It is concluded that thermodynamic approaches have a major contribution to make in developing dose-response models for emerging viruses.


title: How Nurse Scientists Can Stay Productive and On Track During the Pandemic

text: On March 11, 2020, with the declaration of a global pandemic by the World Health Organization, an unplanned slowdown of academic research activities has taken place. While this is not an ideal situation for nurse scientists, it presents a number of unique opportunities for researchers to shift their focus in the short-term, which may actually lead to more productivity in the long-term. This commentary explores ways nurse scientists can stay on track without derailing their plans for career advancement under unprecedented circumstances.


docid: ipnraroq

title: Genome divergence and increased virulence of outbreak associated Salmonella enterica subspecies enterica serovar Heidelberg

text: Salmonella enterica serotype Heidelberg is primarily a poultry adapted serotype of Salmonella that can also colonize other hosts and cause human disease. In this study, we compared the genomes of outbreak associated non-outbreak causing Salmonella ser. Heidelberg strains from diverse hosts and geographical regions. Human outbreak associated strains in this study were from a 2015 multistate outbreak of Salmonella ser. Heidelberg involving 15 states in the United States which originated from bull calves. Our clinicopathologic examination revealed that cases involving Salmonella ser. Heidelberg strains were predominantly young, less than weeks-old, dairy calves. Pre-existing or concurrent disease was found in the majority of the calves. Detection of Salmonella ser. Heidelberg correlated with markedly increased death losses clinically comparable to those seen in herds infected with S. Dublin, a known serious pathogen of cattle. Whole genome based single nucleotide polymorphism based analysis revealed that these calf isolates formed a distinct cluster along with outbreak associated human isolates. The defining feature of the outbreak associated strains, when compared to older isolates of S. Heidelberg, is that all isolates in this cluster contained Saf fimbrial genes which are generally absent in S. Heidelberg. The acquisition of several single nucleotide polymorphisms and the gain of Saf fimbrial genes may have contributed to the increased disease severity of these Salmonella ser. Heidelberg strains. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13099-018-0279-0) contains supplementary material, which is available to authorized users.


title: Antiviral activity of Sambucus FormosanaNakai ethanol extract and related phenolic acid constituents against human coronavirus NL63

text: Abstract Human coronavirus NL63 (HCoV-NL63), one of the main circulating HCoVs worldwide, causes respiratory tract illnesses like runny nose, cough, bronchiolitis and pneumonia. Recently, a severe respiratory illness outbreak of HCoV-NL63 has been reported in a long-term care facility. Sambucus FormosanaNakai, a species of elderberry, is a traditional medicinal herb with anti-inflammatory and antiviral potential. The study investigated the antiviral activity of Sambucus FormosanaNakai stem ethanol extract and some phenolic acid constituents against HCoV-NL63. The extract was less cytotoxic and concentration-dependently increased anti-HCoV-NL63 activities, including cytopathicity, sub-G1 fraction, virus yield (IC50 = 1.17 μg/ml), plaque formation (IC50 = 4.67 μg/ml) and virus attachment (IC50 = 15.75 μg/ml). Among the phenolic acid constituents in Sambucus FormosanaNakai extract, caffeic acid, chlorogenic acid and gallic acid sustained the anti-HCoV-NL63 activity that was ranked in the following order of virus yield reduction: caffeic acid (IC50 = 3.54 μM) > chlorogenic acid (IC50 = 43.45 μM) > coumaric acid (IC50 = 71.48 μM). Caffeic acid significantly inhibited the replication of HCoV-NL63 in a cell-type independent manner, and specifically blocked virus attachment (IC50 = 8.1 μM). Therefore, the results revealed that Sambucus Formosana Nakai stem ethanol extract displayed the strong anti-HCoV-NL63 potential; caffeic acid could be the vital component with anti-HCoV-NL63 activity. The finding could be helpful for developing antivirals against HCoV-NL63.


title: Mental Health Effects of COVID-19 Pandemia: A Review of Clinical and Psychological Traits

text: OBJECTIVE: As the coronavirus (COVID-19) pandemic sweeps across the world, it is causing widespread concern, fear and stress, all of which are natural and normal reactions to the changing and uncertain situation that everyone finds themselves in. METHODS: In this general review, we examined the literature about the psychological effects of COVID-19 pandemia. In total 65 papers were reviewed using the Medline computer database. Only publications in English were selected. RESULTS: Children are likely to be experiencing worry, anxiety and fear and older people are also those with underlying health conditions, having been identified as more vulnerable to COVID-19, can be extremely frightening and very fear-inducing. China and several other countries took strict isolation measures. Medical staff and affiliated healthcare workers (staff) are under both physical and psychological pressure. CONCLUSION: The COVID-19 pandemic is exceptional. Its effect will likely be imprinted on each individual involved. Extensive stressors will emerge or become worsened. Many medical staff workers will be harmfully psychologically affected.


title: From sequence to enzyme mechanism using multi-label machine learning

text: BACKGROUND: In this work we predict enzyme function at the level of chemical mechanism, providing a finer granularity of annotation than traditional Enzyme Commission (EC) classes. Hence we can predict not only whether a putative enzyme in a newly sequenced organism has the potential to perform a certain reaction, but how the reaction is performed, using which cofactors and with susceptibility to which drugs or inhibitors, details with important consequences for drug and enzyme design. Work that predicts enzyme catalytic activity based on 3D protein structure features limits the prediction of mechanism to proteins already having either a solved structure or a close relative suitable for homology modelling. RESULTS: In this study, we evaluate whether sequence identity, InterPro or Catalytic Site Atlas sequence signatures provide enough information for bulk prediction of enzyme mechanism. By splitting MACiE (Mechanism, Annotation and Classification in Enzymes database) mechanism labels to a finer granularity, which includes the role of the protein chain in the overall enzyme complex, the method can predict at 96% accuracy (and 96% micro-averaged precision, 99.9% macro-averaged recall) the MACiE mechanism definitions of 248 proteins available in the MACiE, EzCatDb (Database of Enzyme Catalytic Mechanisms) and SFLD (Structure Function Linkage Database) databases using an off-the-shelf K-Nearest Neighbours multi-label algorithm. CONCLUSION: We find that InterPro signatures are critical for accurate prediction of enzyme mechanism. We also find that incorporating Catalytic Site Atlas attributes does not seem to provide additional accuracy. The software code (ml2db), data and results are available online at http://sourceforge.net/projects/ml2db/ and as supplementary files.


title: Nano-based approach to combat emerging viral (NIPAH virus) infection

text: Abstract Emergence of new virus and their heterogeneity are growing at an alarming rate. Sudden outburst of Nipah virus (NiV) has raised serious question about their instant management using conventional medication and diagnostic measures. A coherent strategy with versatility and comprehensive perspective to confront the rising distress could perhaps be effectuated by implementation of nanotechnology. But in concurrent to resourceful and precise execution of nano-based medication, there is an ultimate need of concrete understanding of the NIV pathogenesis. Moreover, to amplify the effectiveness of nano-based approach in a conquest against NiV, a list of developed nanosystem with antiviral activity is also a prerequisite. Therefore the present review provides a meticulous cognizance of cellular and molecular pathogenesis of NiV. Conventional as well several nano-based diagnosis experimentations against viruses have been discussed. Lastly, potential efficacy of different forms of nano-based systems as convenient means to shield mankind against NiV has also been introduced.


title: Oxidized LDL upregulates macrophage DPP4 expression via TLR4/TRIF/CD36 pathways

text: BACKGROUND: We and others have shown that dipeptidyl peptidase-IV (DPP4) expression is increased in obesity/atherosclerosis and is positively correlated with atherosclerotic burden. However, the mechanism by which DPP4 expression is regulated in obesity remains unclear. In this study, we investigated the pathways regulating the expression of DPP4 on macrophages. METHODS: Flowsight® Imaging Flow Cytometry was employed for the detection of DPP4 and immunophenotyping. DPP4 enzymatic activity was measured by a DPPIV-Glo™ Protease Assay kit. FINDINGS: Human monocytes expressed a moderate level of membrane-bound DPP4. Obese patients with body mass index (BMI) ≥ 30 had a higher level of monocyte DPP4 expression, in parallel with higher levels of HOMA-IR, blood glucose, triglycerides, and non-HDL cholesterol, compared to those in the non-obese (BMI < 30) patients. Oxidized low-density lipoprotein (oxLDL), but not native LDL, up-regulated DPP4 expression on macrophages with a preferential increase in CD36(+) cells. OxLDL mediated DPP4 up-regulation was considerably diminished by Toll-like receptor-4 (TLR4) knockdown and CD36 deficiency. TRIF deficiency, but not MyD88 deficiency, attenuated oxLDL-induced DPP4 increase. INTERPRETATION: Our study suggests a key role for oxLDL and downstream CD36/TLR4/TRIF in regulating DPP4 expression. Increased DPP4 in response to oxidized lipids may represent an integrated mechanism linking post-prandial glucose metabolism to lipoprotein abnormality-potentiated atherosclerosis.


title: Production of mice from a lethal coronavirus infection in the central nervous system by adoptive transfer of virus-specific T cell clones

text: Abstract The protective effect of a mouse hepatitis virus type-4 (MHV-4)-specific CD8+ cytotoxic T cell clone and a CD4+ helper T cell clone was examined by the adoptive transfer into brains of mice lethally infected with MHV-4. Mice survived acute encephalitis if more than 5 × 105 cells of either type of the virus-specific T cell clones had been transfered into H-2-matched recipients by 1 day post-infection. Although the adoptive transfer of both types of the T cell clones suppressed viral growth and viral antigen-positive cells in the brains, a significant inhibition of virus replication by the cytotoxic T cell clone was detected prior to that induced by the helper T cell clone. Histologically, cell destruction was prominent in the brains of mice which received the cytotoxic T cell clone. These results demonstrate that both the CD8+ cytotoxic T cell and the CD4+ helper T cell can protect mice from a lethal MHV-4 infection in the central nervous system.


title: Imatinib-induced irreversible interstitial lung disease: A case report

text: RATIONALE: Imatinib mesylate (imatinib) is a classic tyrosine kinase inhibitor used to treat chronic myeloid leukemia. Although it is well tolerated by most patients and helps in the achievement of complete remission, a few rare imatinib-associated adverse effects such as pulmonary interstitial fibrosis have been reported. Because of its rareity, the clinical features of imatinib-induced interstitial lung disease (ILD) remain unclear. PATIENT CONCERNS: A 49-year-old Chinese man with chronic myeloid leukemia received oral treatment with imatinib and initially exhibited a good response. However, he presented with cough and fever 9 months after treatment initiation. DIAGNOSES: Pulmonary computed tomography indicated diffuse interstitial fibrosis in both lungs. All tests for possible infectious pathologies provided negative results. INTERVENTIONS: The patient was diagnosed with interstitial pneumonia and treated with antibiotics; however, there was no improvement. On the basis of a suspicion of imatinib-induced ILD, imatinib was discontinued and prednisone treatment was initiated. OUTCOMES: The patient's symptoms ameliorated with treatment, and imatinib was reintroduced. However, he developed cough and dyspnea again, and his treatment was switched to nilotinib as a second-line regimen. He was regularly monitored, and although his clinical symptoms ameliorated, computed tomography performed 29 months after he was diagnosed with ILD showed irreversible pulmonary interstitial fibrosis without progression. LESSONS: Clinicians should consider the possibility of severe irreversible ILD and carefully monitor patients receiving imatinib treatment.


title: Foodborne Transmission of Deformed Wing Virus to Ants (Myrmica rubra)

text: Virus host shifts occur frequently, but the whole range of host species and the actual transmission pathways are often poorly understood. Deformed wing virus (DWV), an RNA virus described from honeybees (Apis mellifera), has been shown to have a broad host range. Since ants are often scavenging on dead honeybees, foodborne transmission of these viruses may occur. However, the role of the ant Myrmica rubra as an alternative host is not known and foodborne transmission to ants has not been experimentally addressed yet. Here, we show with a 16-week feeding experiment that foodborne transmission enables DWV type-A and -B to infect M. rubra and that these ants may serve as a virus reservoir. However, the titers of both plus- and minus-sense viral RNA strands decreased over time. Since the ants were fed with highly virus-saturated honeybee pupae, this probably resulted in initial viral peaks, then approaching lower equilibrium titers in infected individuals later. Since DWV infections were also found in untreated field-collected M. rubra colonies, our results support the wide host range of DWV and further suggest foodborne transmission as a so far underestimated spread mechanism.


title: Etiology and Impact of Coinfections in Children Hospitalized With Community-Acquired Pneumonia

text: BACKGROUND: Recognition that coinfections are common in children with community-acquired pneumonia (CAP) is increasing, but gaps remain in our understanding of their frequency and importance. METHODS: We analyzed data from 2219 children hospitalized with CAP and compared demographic and clinical characteristics and outcomes between groups with viruses alone, bacteria alone, or coinfections. We also assessed the frequency of selected pairings of codetected pathogens and their clinical characteristics. RESULTS: A total of 576 children (26%) had a coinfection. Children with only virus detected were younger, more likely to be black, and more likely to have comorbidities such as asthma, compared with children infected with typical bacteria alone. Children with virus-bacterium coinfections had a higher frequency of leukocytosis, consolidation on chest radiography, parapneumonic effusions, intensive care unit admission, and need for mechanical ventilation and an increased length of stay, compared with children infected with viruses alone. Virus-virus coinfections were generally comparable to single-virus infections, with the exception of the need for oxygen supplementation, which was higher during the first 24 hours of hospitalization in some virus-virus pairings. CONCLUSIONS: Coinfections occurred in 26% of children hospitalized for CAP. Children with typical bacterial infections, alone or complicated by a viral infection, have worse outcomes than children infected with a virus alone.


title: Travel restrictions and infectious disease outbreaks

text: BACKGROUND: A key purpose of the IHR is to prevent unwarranted interruptions to trade and travel during large and/or transnational infectious disease outbreaks. Nevertheless, such outbreaks continue to disrupt the travel industry. This aspect of the IHR has received little attention in the academic literature despite its considerable impact on affected States and commercial activity. This paper outlines the challenges and gaps in knowledge regarding the relationship between outbreaks and the travel sector and discusses the opportunities for further research and policy work to overcome these challenges. METHODOLOGY: We conducted a literature review on the relationship between outbreaks and travel restrictions, with a particular focus on the 2014–16 Ebola epidemic in West Africa. This review was complemented by an expert roundtable at Chatham House and further supported by case studies and qualitative interviews. RESULTS: Numerous travel stakeholders are affected by, and affect, large-scale infectious disease outbreaks. These stakeholders react in different ways: peer pressure plays an important role for both governments and the travel sector, and the reactions of the media and public influence and are influenced by these stakeholders. While various data sources on travel are available, and WHO is mandated to work with States, there is no recognised coordinating body to disseminate timely, consistent, reliable and authoritative information and best practices to all stakeholders. CONCLUSION: This article highlights the interdependent relationship between various travel stakeholders. The reasons for interruption of travel during the 2014–16 Ebola outbreak were complex, with decisions by States only partly contributing to the cessation. Decisions by non-state actors, particularly the travel industry itself, contributed significantly and were based on a variety of factors. Further research, analysis and policy development is required to mitigate the health and economic consequences of infectious disease outbreaks. Any further research will also need to take account of COVID-19 travel related issues.


title: MHC class I characterization of Indonesian cynomolgus macaques

text: Cynomolgus macaques (Macaca fascicularis) are quickly becoming a useful model for infectious disease and transplantation research. Even though cynomolgus macaques from different geographic regions are used for these studies, there has been limited characterization of full-length major histocompatibility complex (MHC) class I immunogenetics of distinct geographic populations. Here, we identified 48 MHC class I cDNA nucleotide sequences in eleven Indonesian cynomolgus macaques, including 41 novel Mafa-A and Mafa-B sequences. We found seven MHC class I sequences in Indonesian macaques that were identical to MHC class I sequences identified in Malaysian or Mauritian macaques. Sharing of nucleotide sequences between these geographically distinct populations is also consistent with the hypothesis that Indonesia was a source of the Mauritian macaque population. In addition, we found that the Indonesian cDNA sequence Mafa-B*7601 is identical throughout its peptide binding domain to Mamu-B*03, an allele that has been associated with control of Simian immunodeficiency virus (SIV) viremia in Indian rhesus macaques. Overall, a better understanding of the MHC class I alleles present in Indonesian cynomolgus macaques improves their value as a model for disease research, and it better defines the biogeography of cynomolgus macaques throughout Southeast Asia.


title: The use of sialidase therapy for respiratory viral infections

text: Abstract DAS181 is an inhaled bacterial sialidase which functions by removing sialic acid (Sia) from the surface of epithelial cells, preventing attachment and subsequent infection by respiratory viruses that utilize Sia as a receptor. DAS181 is typical of bacterial sialidases in cleaving Sia α2-3 and Sia α2-6 linkages, and it also has a demonstrated effect against acetylated and hydroxylated forms of Sia. The potency of the compound has been enhanced by coupling the active sialidase with an amphiregulin tag, allowing a longer duration of action and minimizing spread to the systemic circulation. DAS181 is now in Phase II development for the treatment of influenza, and it has also demonstrated activity in individual cases of parainfluenza in immunosuppressed patients. Continued evaluation of the roles and activities of bacterial sialidases is required to expand the range of successful antiviral therapies targeting Sia or its derivatives.


Ensuring optimal utilization of personal protective equipment in the coronavirus disease-2019 pandemic


title: Detection of hepatitis E virus and other livestock-related pathogens in Iowa streams

text: Abstract Manure application is a source of pathogens to the environment. Through overland runoff and tile drainage, zoonotic pathogens can contaminate surface water and streambed sediment and could affect both wildlife and human health. This study examined the environmental occurrence of gene markers for livestock-related bacterial, protozoan, and viral pathogens and antibiotic resistance in surface waters within the South Fork Iowa River basin before and after periods of swine manure application on agricultural land. Increased concentrations of indicator bacteria after manure application exceeding Iowa's state bacteria water quality standards suggest that swine manure contributes to diminished water quality and may pose a risk to human health. Additionally, the occurrence of HEV and numerous bacterial pathogen genes for Escherichia coli, Enterococcus spp., Salmonella sp., and Staphylococcus aureus in both manure samples and in corresponding surface water following periods of manure application suggests a potential role for swine in the spreading of zoonotic pathogens to the surrounding environment. During this study, several zoonotic pathogens were detected including Shiga-toxin producing E. coli, Campylobacter jejuni, pathogenic enterococci, and S. aureus; all of which can pose mild to serious health risks to swine, humans, and other wildlife. This research provides the foundational understanding required for future assessment of the risk to environmental health from livestock-related zoonotic pathogen exposures in this region. This information could also be important for maintaining swine herd biosecurity and protecting the health of wildlife near swine facilities.


title: Targeting of Moloney murine leukemia virus gag precursor to the site of virus budding

text: Retrovirus Moloney murine leukemia virus (M-MuLV) matures by budding at the cell surface. Central to the budding process is the myristoylated viral core protein precursor Gag which, even in the absence of all other viral components, is capable of associating with the cytoplasmic leaflet of the plasma membrane and assembling into extracellular virus- like particles. In this paper we have used heterologous, Semliki Forest virus-driven, expression of M-MuLV Gag to study the mechanism by which this protein is targeted to the cell surface. In pulse-chase experiments, BFA, monensin, and 20 degrees C block did not affect incorporation of Gag into extracellular particles thereby indicating that the secretory pathway is not involved in targeting of Gag to the cell surface. Subcellular fractionation studies demonstrated that newly synthesized Gag became rapidly and efficiently associated with membranes which had a density similar to that of plasma membrane- derived vesicles. Protease-protection studies confirmed that the Gag- containing membranes were of plasma membrane origin, since in crude cell homogenates, the bulk of newly synthesized Gag was protease- resistant as expected of a protein that binds to the cytoplasmic leaflet of the plasma membrane. Taken together these data indicate that targeting of M-MuLV Gag to the cell surface proceeds via direct insertion of the protein to the cytoplasmic side of the plasma membrane. Furthermore, since the membrane insertion reaction is highly efficient and specific, this suggests that the reaction is dependent on as-yet-unidentified cellular factors.


Quelle conduite à tenir adopter vis à vis des injections intravitréennes (IVT) dans cette période d’épidémie au Covid-19 – SARS-CoV-2 ?


title: Changes in Population Dynamics in Mutualistic versus Pathogenic Viruses

text: Although generally regarded as pathogens, viruses can also be mutualists. A number of examples of extreme mutualism (i.e., symbiogenesis) have been well studied. Other examples of mutualism are less common, but this is likely because viruses have rarely been thought of as having any beneficial effects on their hosts. The effect of mutualism on the population dynamics of viruses is a topic that has not been addressed experimentally. However, the potential for understanding mutualism and how a virus might become a mutualist may be elucidated by understanding these dynamics.


title: Interfering Waves of Adaptation Promote Spatial Mixing

text: A fundamental problem of asexual adaptation is that beneficial substitutions are not efficiently accumulated in large populations: Beneficial mutations often go extinct because they compete with one another in going to fixation. It has been argued that such clonal interference may have led to the evolution of sex and recombination in well-mixed populations. Here, we study clonal interference, and mechanisms of its mitigation, in an evolutionary model of spatially structured populations with uniform selection pressure. Clonal interference is much more prevalent with spatial structure than without, due to the slow wave-like spread of beneficial mutations through space. We find that the adaptation speed of asexuals saturates when the linear habitat size exceeds a characteristic interference length, which becomes shorter with smaller migration and larger mutation rate. The limiting speed is proportional to μ(1/2) and μ(1/3) in linear and planar habitats, respectively, where the mutational supply μ is the product of mutation rate and local population density. This scaling and the existence of a speed limit should be amenable to experimental tests as they fall far below predicted adaptation speeds for well-mixed populations (that scale as the logarithm of population size). Finally, we show that not only recombination, but also long-range migration is a highly efficient mechanism of relaxing clonal competition in structured populations. Our conservative estimates of the interference length predict prevalent clonal interference in microbial colonies and biofilms, so clonal competition should be a strong driver of both genetic and spatial mixing in those contexts.


title: (1)H, (13)C and (15)N resonance assignments of SARS-CoV main protease N-terminal domain

text: The main protease (M(pro)) of severe acute respiratory syndrome coronavirus (SARS-CoV) plays an essential role in the extensive proteolytic processing of the viral polyproteins (pp1a and pp1ab), and it is an important target for anti-SARS drug development. SARS-CoV M(pro) is composed of a catalytic N-terminal domain and an α-helical C-terminal domain linked by a long loop. Even though the N-terminal domain of SARS-CoV M(pro) adopts a similar chymotrypsin-like fold as that of piconavirus 3C protease, the extra C-terminal domain is required for SARS-CoV M(pro) to be enzymatically active. Here, we reported the NMR assignments of the SARS-CoV M(pro) N-terminal domain alone, which are essential for its solution structure determination.


title: African trypanosomiasis: Sensitive and rapid detection of the sub-genus Trypanozoon by loop-mediated isothermal amplification (LAMP) of parasite DNA

text: Abstract Control of human African trypanosomiasis (HAT) is dependent on accurate diagnosis and treatment of infected patients. However, sensitivities of tests in routine use are unsatisfactory, due to the characteristically low parasitaemias in naturally infected individuals. We have identified a conserved sequence in the repetitive insertion mobile element (RIME) of the sub-genus Trypanozoon and used it to design primers for a highly specific loop-mediated isothermal amplification (LAMP) test. The test was used to analyse Trypanozoon isolates and clinical samples from HAT patients. The RIME LAMP assay was performed at 62°C using real-time PCR and a water bath. DNA amplification was detectable within 25min. All positive samples detected by gel electrophoresis or in real-time using SYTO-9 fluorescence dye could also be detected visually by addition of SYBR Green I to the product. The amplicon was unequivocally confirmed through restriction enzyme NdeI digestion, analysis of melt curves and sequencing. The analytical sensitivity of the RIME LAMP assay was equivalent to 0.001 trypanosomes/ml while that of classical PCR tests ranged from 0.1 to 1000 trypanosomes/ml. LAMP detected all 75 Trypanozoon isolates while TBR1 and two primers (specific for sub-genus Trypanozoon) showed a sensitivity of 86.9%. The SRA gene PCR detected 21 out of 40 Trypanosoma brucei rhodesiense isolates while Trypanosoma gambiense-specific glycoprotein primers (TgsGP) detected 11 out of 13 T. b. gambiense isolates. Using clinical samples, the LAMP test detected parasite DNA in 18 out of 20 samples which included using supernatant prepared from boiled blood, CSF and direct native serum. The sensitivity and reproducibility of the LAMP assay coupled with the ability to detect the results visually without the need for sophisticated equipment indicate that the technique has strong potential for detection of HAT in clinical settings. Since the LAMP test shows a high tolerance to different biological substances, determination of the appropriate protocols for processing the template to make it a user-friendly technique, prior to large scale evaluation, is needed.


title: Contentious issues and evolving concepts in the clinical presentation and management of patients with COVID-19 infectionwith reference to use of therapeutic and other drugs used in Co-morbid diseases (Hypertension, diabetes etc)

text: Abstract Background and aims Multiple issues in management of COVID have emerged, but confusion persists regarding rational interpretation. Aim of this brief review is to review these issues based on current literature. Methods This is a narrative review with Pubmed and Google Scholar search till 23 March 2020. Search terms were, COVID-19, treatment of coronavirus, COVID 19 and following terms; chloroquine, hydroxychloroquine, ibuprofen, ACE-inhibitors or angiotensin receptor blockers, cardiovascular disease, diarrhoea, liver, testis and gastrointestinal disease. Results We discuss evidence regarding role of chloroquine and hydroxychloroquine in treatment and prophylaxis, use of inhibitors of the renin angiotensin system, safety of ibuprofen, unusual clinical features like gastrointestinal symptoms and interpretation of tests for cardiac enzymes and biomarkers. Conclusions While our conclusions on management of COVID-19 patients with co-morbidities are based on current evidence, however, data is limited and there is immediate need for fast track research.


title: Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines

text: Viral vaccine vectors have shown to be effective in inducing a robust immune response against the vaccine antigen. Newcastle disease virus (NDV), an avian paramyxovirus, is a promising vaccine vector against human and veterinary pathogens. Avirulent NDV strains LaSota and B1 have long track records of safety and efficacy. Therefore, use of these strains as vaccine vectors is highly safe in avian and non-avian species. NDV replicates efficiently in the respiratory track of the host and induces strong local and systemic immune responses against the foreign antigen. As a vaccine vector, NDV can accommodate foreign sequences with a good degree of stability and as a RNA virus, there is limited possibility for recombination with host cell DNA. Using NDV as a vaccine vector in humans offers several advantages over other viral vaccine vectors. NDV is safe in humans due to host range restriction and there is no pre-existing antibody to NDV in the human population. NDV is antigenically distinct from common human pathogens. NDV replicates to high titer in a cell line acceptable for human vaccine development. Therefore, NDV is an attractive vaccine vector for human pathogens for which vaccines are currently not available. NDV is also an attractive vaccine vector for animal pathogens.


title: Minimizing the risk of COVID-19 among patients on dialysis

text: Patients on haemodialysis or peritoneal dialysis are likely to be at increased risk of novel coronavirus disease (COVID-19). Preventive strategies must be implemented to minimize the risk of disease transmission in dialysis facilities, including education of staff and patients, screening for COVID-19 and separation of infected or symptomatic and non-infected patients.


title: Effectiveness and safety of glucocorticoids to treat COVID-19: a rapid review and meta-analysis.

text: Background Glucocorticoids are widely used in the treatment of various pulmonary inflammatory diseases, but they are also often accompanied by significant adverse reactions. Published guidelines point out that low dose and short duration systemic glucocorticoid therapy may be considered for patients with rapidly progressing coronavirus disease 2019 (COVID-19) while the evidence is still limited. Methods We comprehensively searched electronic databases and supplemented the screening by conducting a manual search. We included randomized controlled trials (RCTs) and cohort studies evaluating the effectiveness and safety of glucocorticoids in children and adults with COVID-19, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and conducted meta-analyses of the main indicators that were identified in the studies. Results Our search retrieved 23 studies, including one RCT and 22 cohort studies, with a total of 13,815 patients. In adults with COVID-19, the use of systemic glucocorticoid did not reduce mortality [risk ratio (RR) =2.00, 95% confidence interval (CI): 0.69 to 5.75, I2=90.9%] or the duration of lung inflammation [weighted mean difference (WMD) =-1 days, 95% CI: -2.91 to 0.91], while a significant reduction was found in the duration of fever (WMD =-3.23 days, 95% CI: -3.56 to -2.90). In patients with SARS, glucocorticoids also did not reduce the mortality (RR =1.52, 95% CI: 0.89 to 2.60, I2=84.6%), duration of fever (WMD =0.82 days, 95% CI: -2.88 to 4.52, I2=97.9%) or duration of lung inflammation absorption (WMD =0.95 days, 95% CI: -7.57 to 9.48, I2=94.6%). The use of systemic glucocorticoid therapy prolonged the duration of hospital stay in all patients (COVID-19, SARS and MERS). Conclusions Glucocorticoid therapy was found to reduce the duration of fever, but not mortality, duration of hospitalization or lung inflammation absorption. Long-term use of high-dose glucocorticoids increased the risk of adverse reactions such as coinfections, so routine use of systemic glucocorticoids for patients with COVID-19 cannot be recommend.


title: Management guidelines for obstetric patients and neonates born to mothers with suspected or probable severe acute respiratory syndrome (SARS) No. 225, April 2009

text: Abstract Objective This document summarizes the limited experience of SARS in pregnancy and suggests guidelines for management. Outcomes Cases reported from Asia suggest that maternal and fetal outcomes are worsened by SARS during pregnancy. Evidence Medline was searched for relevant articles published in English from 2000 to 2007. Case reports were reviewed and expert opinion sought. Values Recommendations were made according to the guidelines developed by the Canadian Task Force on Preventive Health Care.


title: Nivolumab-induced Myocarditis Successfully Treated with Corticosteroid Therapy: A Case Report and Review of the Literature

text: A 62-year-old man presented to our hospital for the further evaluation and treatment of his back pain, general fatigue, and dyspnea, which had developed 4 days after the 29th administration of nivolumab to treat his lung cancer. Based on his clinical history, elevated serum cardiac enzyme values, and cardiac magnetic resonance (CMR) imaging and myocardial biopsy findings, he was diagnosed with myocarditis induced by nivolumab. Corticosteroid therapy improved his condition, and CMR performed on hospital day 11 also showed remarkable improvement. Although nivolumab-induced myocarditis is rare, cardiologists should consider it when encountering patients treated with such a drug for malignant disease.


title: Structural Bases of Coronavirus Attachment to Host Aminopeptidase N and Its Inhibition by Neutralizing Antibodies

text: The coronaviruses (CoVs) are enveloped viruses of animals and humans associated mostly with enteric and respiratory diseases, such as the severe acute respiratory syndrome and 10–20% of all common colds. A subset of CoVs uses the cell surface aminopeptidase N (APN), a membrane-bound metalloprotease, as a cell entry receptor. In these viruses, the envelope spike glycoprotein (S) mediates the attachment of the virus particles to APN and subsequent cell entry, which can be blocked by neutralizing antibodies. Here we describe the crystal structures of the receptor-binding domains (RBDs) of two closely related CoV strains, transmissible gastroenteritis virus (TGEV) and porcine respiratory CoV (PRCV), in complex with their receptor, porcine APN (pAPN), or with a neutralizing antibody. The data provide detailed information on the architecture of the dimeric pAPN ectodomain and its interaction with the CoV S. We show that a protruding receptor-binding edge in the S determines virus-binding specificity for recessed glycan-containing surfaces in the membrane-distal region of the pAPN ectodomain. Comparison of the RBDs of TGEV and PRCV to those of other related CoVs, suggests that the conformation of the S receptor-binding region determines cell entry receptor specificity. Moreover, the receptor-binding edge is a major antigenic determinant in the TGEV envelope S that is targeted by neutralizing antibodies. Our results provide a compelling view on CoV cell entry and immune neutralization, and may aid the design of antivirals or CoV vaccines. APN is also considered a target for cancer therapy and its structure, reported here, could facilitate the development of anti-cancer drugs.


title: CNS Tuberculosis

text: Tuberculous meningitis is a subacute meningitis in which early therapy significantly improves outcome. Atypical features abound, and the diagnosis must be entertained in a variety of situations. CT scanning has improved our knowledge of the disease and may help in diagnosis.


title: Pathogen Epidemiology

text: Abstract Infectious disease epidemiology makes use of mathematical models and molecular typing methods to probe pathogen transmission. Models and the basic reproductive number R 0 are a powerful tool for understanding disease dynamics and the impact of interventions, while genetic methods to characterize infectious agents give us an increasingly highly resolved picture of transmission over the short term of outbreaks, and the longer term of international spread. These two approaches are complementary, and are being combined in an approach termed ‘phylodynamics’ which aims to understand disease dynamics by the analysis of genetic data.


title: Viruses Associated With Foodborne Infections

text: Abstract Foodborne pathogens cause acute and chronic health outcomes of very different durations, severity and mortality, resulting in high costs and burdens to society. The issues of food safety and food poisoning are being increasingly emphasised, particularly in developed countries. Infection/contamination with many agents i.e., bacterial, parasitic and viral entities can result in foodborne illness. This article will focus mainly on viral agents of infection. A range of different viruses can cause food poisoning/foodborne infection, and infection can result in a myriad of symptoms, ranging from mild, acute disease to chronic, debilitating disease and even death. Due to the inherent differences between bacteria and viruses, namely the fact that viruses do not replicate in food, while bacteria do, viruses are frequently difficult to detect. This is compounded by the fact that many of the viruses associated with enteric disease do not replicate in cell culture. These factors can lead to a lag between reporting, detection and analysis of foodborne viruses versus bacterial agents. Despite these constraints, it is now evident that there are both well-established and emerging viruses implicated in foodborne infections, and the role of molecular detection and characterisation is becoming increasingly important.


title: Innate immune response to viral infection of the lungs

text: Summary Viral respiratory tract infections are the most common infectious illnesses, though they are usually self-limiting and confined to the respiratory tract. The rapid identification of viruses and their effective elimination with minimal local and systemic inflammation is a testament to the efficiency of the innate immune response within the airways and lungs. A failure of this response appears to occur in those with asthma and chronic obstructive pulmonary disease, where viral infection is an important trigger for acute exacerbations. The innate immune response to viruses requires their early detection through pathogen recognition receptors and the recruitment of the efficient antiviral response that is centred around the release of type 1 interferons. The airway epithelium provides both a barrier and an early detector for viruses, and interacts closely with cells of the innate immune response, especially macrophages and dendritic cells, to eliminate infection and trigger a specific adaptive immune response.


title: Molecular characterisation of RIG-I-like helicases in the black flying fox, Pteropus alecto

text: The RIG-I like helicases, RIG-I, mda5 and LGP2 are an evolutionarily conserved family of cytosolic pattern recognition receptors important in the recognition of viral RNA, and responsible for the innate induction of interferons and proinflammatory cytokines upon viral infection. Bats are natural reservoir hosts to a variety of RNA viruses that cause significant morbidity and mortality in other species; however the mechanisms responsible for the control of viral replication in bats are not understood. This report describes the molecular cloning and expression analysis of RIG-I, mda5 and LGP2 genes in the fruit bat Pteropus alecto, and is the first description of RIG-I like helicases from any species of bat. Our results demonstrate that P. alecto RIG-I, mda5 and LGP2 have similar primary structures and tissue expression patterns to their counterparts in humans and other mammals. Stimulation of bat kidney cells with synthetic dsRNA (poly I:C) induced high levels of interferon β and rapid upregulation of all three helicases. These findings reveal that the cytoplasmic virus sensing machinery is present and intact in P. alecto. This study provides the foundation for further investigations into the interactions between bat RIG-I-like helicases and viruses to elucidate the mechanisms responsible for the asymptomatic nature of viral infections in bats.


title: Review of companion animal viral diseases and immunoprophylaxis

text: In this article we review important established, newly emergent and potential viral diseases of cats, dogs and rabbits. Topics covered include virus epidemiology, disease pathogenesis, existing and prospective immunoprophylaxis against the viruses. For some feline viruses, notably the immunodeficiency virus, leukaemia virus and peritonitis virus, available vaccines are poorly efficacious but there are good prospects for this. A further challenge for the industry is likely to be due to viruses jumping species and the emergence of more virulent variants of established viruses resulting from mutations as has been the case for the canine parvovirus, coronaviruses and feline calicivirus.


title: Imaging of Coronavirus Disease 2019: A Chinese Expert Consensus Statement

text: Abstract Coronavirus disease 2019 (COVID-19) is highly contagious, mainly causing inflammatory lesions in the lungs, and can also cause damage to the intestine and liver. The rapid spread of the virus that causes coronavirus disease 2019 (COVID-19) pneumonia has posed complex challenges to global public health. Early detection, isolation, diagnosis, and treatment are the most effective means of prevention and control. At present, the epidemic situation of new coronavirus infection has tended to be controlled in China, and it is still in a period of rapid rise in much of the world. The current gold standard for the diagnosis of COVID-19 is the detection of coronavirus nucleic acids, but imaging has an important role in the detection of lung lesions, stratification, evaluation of treatment strategies, and differentiation of mixed infections. This Chinese expert consensus statement summarizes the imaging features of COVID-19 pneumonia and may help radiologists across the world to understand this disease better.


title: Multifaceted Functions of Host Cell Caveolae/Caveolin-1 in Virus Infections

text: Virus infection has drawn extensive attention since it causes serious or even deadly diseases, consequently inducing a series of social and public health problems. Caveolin-1 is the most important structural protein of caveolae, a membrane invagination widely known for its role in endocytosis and subsequent cytoplasmic transportation. Caveolae/caveolin-1 is tightly associated with a wide range of biological processes, including cholesterol homeostasis, cell mechano-sensing, tumorigenesis, and signal transduction. Intriguingly, the versatile roles of caveolae/caveolin-1 in virus infections have increasingly been appreciated. Over the past few decades, more and more viruses have been identified to invade host cells via caveolae-mediated endocytosis, although other known pathways have been explored. The subsequent post-entry events, including trafficking, replication, assembly, and egress of a large number of viruses, are caveolae/caveolin-1-dependent. Deprivation of caveolae/caveolin-1 by drug application or gene editing leads to abnormalities in viral uptake, viral protein expression, or virion release, whereas the underlying mechanisms remain elusive and must be explored holistically to provide potential novel antiviral targets and strategies. This review recapitulates our current knowledge on how caveolae/caveolin-1 functions in every step of the viral infection cycle and various relevant signaling pathways, hoping to provide a new perspective for future viral cell biology research.


title: Controlling infectious disease outbreaks in low-income and middle-income countries

text: When an infectious disease outbreak is detected or suspected, a healthcare facility’s infection control personnel should be notified and an outbreak control team formed that is pertinent to the size and severity of the outbreak and healthcare facility. Management of an infectious disease outbreak in a middle- or low-income country is challenging. Cost-effective recommendations that are easy to carry out and that have been stratified according to the type of infection and prevention and control intervention used are provided in this paper and constitute basic practices.


docid: cnndsjyf

title: Data stream dataset of SARS-CoV-2 genome

text: As of May 25, 2020, the novel coronavirus disease (called COVID-19) spread to more than 185 countries/regions with more than 348,000 deaths and more than 5,550,000 confirmed cases. In the bioinformatics area, one of the crucial points is the analysis of the virus nucleotide sequences using approaches such as data stream techniques and algorithms. However, to make feasible this approach, it is necessary to transform the nucleotide sequences string to numerical stream representation. Thus, the dataset provides four kinds of data stream representation (DSR) of SARS-CoV-2 virus nucleotide sequences. The dataset provides the DSR of 1557 instances of SARS-CoV-2 virus, 11540 other instances of other viruses from the Virus-Host DB dataset, and three instances of Riboviria viruses from NCBI (Betacoronavirus RaTG13, bat-SL-CoVZC45, and bat-SL-CoVZXC21).


title: Comorbidities impact on the prognosis of severe acute community-acquired pneumonia

text: Community-acquired pneumonia (CAP) is a frequent cause of admission to hospital worldwide with high mortality rates. Host comorbidities may be associated not just with a greater risk of developing the disease but also with worse outcomes. In this work, the evaluation of the impact of host comorbidities on the prognosis of severe CAP patients admitted to an Intensive Care Unit (ICU) was proposed. Severity indexes, some clinical and analytic parameters at admission in ICU as well as patient comorbidities were analyzed and statistically compared with mortality. In this study, although there was no clear link between comorbidities and mortality, factors such as smoking, obesity and previous renal disease impairment seem to have an impact on the prognosis of severe CAP.


title: High Pulmonary Levels of IL-6 and IL-1β in Children with Chronic Suppurative Lung Disease Are Associated with Low Systemic IFN-γ Production in Response to Non-Typeable Haemophilus influenzae

text: Non-typeable Haemophilus influenzae (NTHi) is commonly associated with chronic suppurative lung disease in children. We have previously shown that children with chronic suppurative lung disease have a reduced capacity to produce IFN-γ in response to NTHi compared with healthy control children. The aim of this study was to determine if deficient NTHi-specific IFN-γ production is associated with heightened systemic or airway inflammation. We measured a panel of cytokines (IFN-γ, IL-1β, IL-6, IL-8, IL-12 p70), antimicrobial proteins (LL-37, IP-10) as well as cellular and clinical factors associated with airway and systemic inflammation in 70 children with chronic suppurative lung disease. IFN-γ was measured in peripheral blood mononuclear cells challenged in vitro with live NTHi. Regression analysis was used to assess the association between the systemic and airway inflammation and the capacity to produce IFN-γ. On multivariate regression, NTHi-specific IFN-γ production was significantly negatively associated with the BAL concentrations of the inflammatory cytokines IL-6 (β=-0.316; 95%CI -0.49, -0.14; p=0.001) and IL-1β (β=-0.023; 95%CI -0.04, -0.01; p=0.001). This association was independent of bacterial or viral infection, BAL cellularity and the severity of bronchiectasis (using modified Bhalla score on chest CT scans). We found limited evidence of systemic inflammation in children with chronic suppurative lung disease. In summary, increased local airway inflammation is associated with a poorer systemic cell-mediated immune response to NTHi in children with chronic suppurative lung disease. These data support the emerging body of evidence that impaired cell-mediated immune responses and dysregulated airway inflammation may be linked and contribute to the pathobiology of chronic suppurative lung disease.


title: SARS‐CoV‐2 infection in kidney transplant recipients: Early report of five cases

text: From December 2019 to March 2020, China was the epicenter of the SARS‐CoV‐2 infection pandemic, but from that moment on, Europe surpassed China in the number of new cases and deaths related to this novel viral respiratory infection. The emergence of this world pandemic is particularly important for solid organ transplant recipients, who might have an increased risk of mortality, not only due to their chronic immunosuppression status, but also to the cardiovascular risk that correlates with several years of chronic kidney disease. To the extent that there is still a lack of knowledge about the clinical characteristics, evolution, and prognosis of SARS‐CoV‐2 infection in kidney transplant recipients, we will report the first 5 cases diagnosed and followed in our transplant unit, as well as share the therapeutic strategies adopted.


docid: tqkagpwt

title: Relationship between CD14-159C/T gene polymorphism and acute brucellosis risk

text: Abstract Objective To investigate the association between the cluster of differentiation 14 (CD14)-159C/T (rs2569190) gene polymorphism and susceptibility to acute brucellosis in an Iranian population. Methods The study included 153 Iranian patients with active brucellosis and 128 healthy individuals as the control group. Genotyping of the CD14 variant was performed using an amplification refractory mutation system-polymerase chain reaction method. Results The prevalence of CD14-159 TT and CT genotypes were associated with increased risk of brucellosis [odds ratio (OR) = 1.993, 95% confidence interval (95% CI) = 1.07–3.71, P = 0.03 for CT; OR = 3.869, 95% CI = 1.91–7.84, P = 0.01 for TT genotype. Additionally, the minor allele (T) was significantly more frequently present in brucellosis patients than in controls (61% vs. 45%, respectively), and was a risk factor for brucellosis (OR = 3.058, 95% CI = 1.507–6.315, P = 0.01). Conclusions The findings provided suggestive evidence of association of the CD14-159C/T gene polymorphism with susceptibility to acute brucellosis in the Iranian population.


title: Distinct Gene Profiles of Bone Marrow-Derived Macrophages and Microglia During Neurotropic Coronavirus-Induced Demyelination

text: Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by demyelination and axonal loss. Demyelinating lesions are associated with infiltrating T lymphocytes, bone marrow-derived macrophages (BMDM), and activated resident microglia. Tissue damage is thought to be mediated by T cell produced cytokines and chemokines, which activate microglia and/or BMDM to both strip myelin and produce toxic factors, ultimately damaging axons and promoting disability. However, the relative contributions of BMDM and microglia to demyelinating pathology are unclear, as their identification in MS tissue is difficult due to similar morphology and indistinguishable surface markers when activated. The CD4 T cell-induced autoimmune murine model of MS, experimental autoimmune encephalitis (EAE), in which BMDM are essential for demyelination, has revealed pathogenic and repair-promoting phenotypes associated with BMDM and microglia, respectively. Using a murine model of demyelination induced by a gliatropic coronavirus, in which BMDM are redundant for demyelination, we herein characterize gene expression profiles of BMDM versus microglia associated with demyelination. While gene expression in CNS infiltrating BMDM was upregulated early following infection and subsequently sustained, microglia expressed a more dynamic gene profile with extensive mRNA upregulation coinciding with peak demyelination after viral control. This delayed microglia response comprised a highly pro-inflammatory and phagocytic profile. Furthermore, while BMDM exhibited a mixed phenotype of M1 and M2 markers, microglia repressed the vast majority of M2-markers. Overall, these data support a pro-inflammatory and pathogenic role of microglia temporally remote from viral control, whereas BMDM retained their gene expression profile independent of the changing environment. As demyelination is caused by multifactorial insults, our results highlight the plasticity of microglia in responding to distinct inflammatory settings, which may be relevant for MS pathogenesis.


title: Influenza and respiratory syncytial virus screening for the detection of asymptomatically infected patients in hematology and oncology

text: Introduction: Respiratory syncytial virus (RSV) and influenza virus infections are a significant healthcare risk for immunocompromised patients. In addition to community onset, nosocomial acquisition and transmission may also occur. Detection of asymptomatic shedders (e.g., patients in the incubation period or immunosuppressed long term shedders) facilitates control of nosocomial transmission. Methods: To strengthen the existing infection control concept, a PCR-based screening for RSV and influenza virus was implemented for all patients lacking respiratory symptoms (asymptomatic patients) who were hospitalized on an adult and a pediatric hemato-oncological ward. Laboratory results of this screening were analyzed retrospectively. Results: 665 respiratory specimens were obtained for screening from 251 patients (26% were 18 years and younger) from December 2016 to April 2017. In 23 patients without respiratory symptoms, either influenza virus or RSV infection was found, resulting in a detection rate of about 9%. In 6 patients, the infection was presumably detected during the incubation period, because an increase of viral load was observed in subsequent specimens. Positive screening results facilitated timely implementation of adequate infection control precautions. Nosocomial clusters of RSV or influenza were not detected during the screening period on the two wards. Conclusion: The seasonal screening program expanded our existing infection control concept in terms of patients lacking respiratory symptoms who shed influenza virus or RSV. It enabled us to identify 23 RSV or influenza infections in patients lacking respiratory symptoms in a 4-month period and thus to rapidly take isolation precautions.


title: Comprehensive assessment showed no associations of variants at the SLC10A1 locus with susceptibility to persistent HBV infection among Southern Chinese

text: The sodium taurocholate cotransporting polypeptide (NTCP) encoded by SLC10A1 was recently demonstrated to be a functional receptor for hepatitis B virus (HBV). The role of SLC10A1 polymorphisms, particularly the Ser267Phe variant (rs2296651) in exon 4, has been frequently investigated in regard to risk of persistent HBV infection. However, these investigations have generated conflicting results. To examine whether common genetic variation at the SLC10A1 locus is associated with risk of persistent HBV infection, haplotype-tagging and imputed single nucleotide polymorphisms (SNPs) were assessed in two case-control sample sets, totally including 2,550 cases (persistently HBV infected subjects, PIs) and 2,124 controls (spontaneously recovered subjects, SRs) of Southern Chinese ancestry. To test whether rare or subpolymorphic SLC10A1 variants are associated with disease risk, the gene’s exons in 244 cases were sequenced. Overall, we found neither SNPs nor haplotypes of SLC10A1 showed significant association in the two sample sets. Furthermore, no significant associations of rare variants or copy number variation covering SLC10A1 were observed. Finally, expression quantitative trait locus analyses revealed that SNPs potentially affecting SLC10A1 expression also showed no significant associations. We conclude that genetic variation at the SLC10A1 locus is not likely a major risk factor of persistent HBV infection among Southern Chinese.


title: Integrating COVID‐19 Volunteer Response into the Year 3 MD Curriculum

text: The University of British Columbia (UBC) Faculty of Medicine suspended clinical rotations for medical students on March 14, 2020 due to the COVID‐19 pandemic. At that time 291 Year 3 medical students were engaged in clerkships across British Columbia and urgently needed an academic pathway to advance to Year 4 on schedule.


title: Construction of Armored RNA Containing Long-Size Chimeric RNA by Increasing the Number and Affinity of the Pac Site in Exogenous RNA and Sequence Coding Coat Protein of the MS2 Bacteriophage

text: OBJECTIVES: To construct a one-plasmid expression system of the armored RNA containing long chimeric RNA byincreasing the number and affinity of the pac site. METHODS: The plasmid pET-MS2-pac was constructedwith one C-variant pac site, and then the plasmid pM-CR-2C containing 1,891-bp chimeric sequences and two C-variant pac sites was produced. Meanwhile, three plasmids (pM-CR-C, pM-CR-2W and pM-CR-W) were obtained as parallel controls with a different number and affinity of the pac site. Finally, the armored RNA was expressed and purified. RESULTS: The armored RNA with 1,891 bases target RNA was expressed successfully by the one-plasmid expression system with two C-variant pac sites, while for one pac site, no matter whether the affinity was changed or not, only the 1,200 bases target RNA was packaged. It was also found that the C-variant pac site could increase the expression efficiency of the armored RNA. The armored RNA with 1,891-bp exogenous RNA in our study showed the characterization of ribonuclease resistance and stability at different time points and temperature conditions. CONCLUSIONS: The armored RNA with 1,891 bases exogenous RNA was constructed and the expression system can be used as a platform for preparation of the armored RNA containing long RNA sequences.


COVID‐19 a personal reflection


Schamberg‐like purpuric eruptions and tonsillitis in mild COVID‐19


docid: ajcwapvt

title: Potential biases arising from epidemic dynamics in observational seroprotection studies

text: The extent and duration of immunity following SARS-CoV-2 infection are critical outstanding questions about the epidemiology of this novel virus, and studies are needed to evaluate the effects of serostatus on reinfection. Understanding the potential sources of bias and methods to alleviate biases in these studies is important for informing their design and analysis. Confounding by individual-level risk factors in observational studies like these is relatively well appreciated. Here, we show how geographic structure and the underlying, natural dynamics of epidemics can also induce noncausal associations. We take the approach of simulating serologic studies in the context of an uncontrolled or a controlled epidemic, under different assumptions about whether prior infection does or does not protect an individual against subsequent infection, and using various designs and analytic approaches to analyze the simulated data. We find that in studies assessing the efficacy of serostatus on future infection, comparing seropositive individuals to seronegative individuals with similar time-dependent patterns of exposure to infection, by stratifying or matching on geographic location and time of enrollment, is essential to prevent bias.


title: 8 Enhancing hygiene/antimicrobial properties of polyolefins

text: Abstract The unique characteristics of polyolefins make them the best candidates in single use healthcare products, medical textiles, and water filters. Most medical textiles and polymeric materials used in hospitals and hotels are good media for cross-transmission of diseases since most microorganisms can survive on fibrous materials for several hours to several months. Use of medical devices with antimicrobial functions has been considered as a major avenue to fight against microbial infections. In addition, suitable packaging can slow the deterioration rate, and hence, extend the shelf-life of food. Physical and chemical incorporation of antimicrobial agents into polyolefins can be implemented in common polyolefin processing. In this chapter, antimicrobial polyolefins are summarized based on processes that were studied to incorporate biocides into the polymers. These processes include blending, coating, and chemical modifications.


title: Collateral damage – Impact of a pandemic on stroke emergency services

text: BACKGROUND: The COVID-19 pandemic's impact on stroke care is two-fold — direct impact of the infection and indirect impact on non-COVID-19 diseases. Anecdotal evidence and clinical observation suggest that there is a decrease in the number of patients presenting with stroke during the pandemic. We aim to understand the impact of the COVID-19 pandemic on the utilization of stroke emergency services on a single comprehensive stroke center (CSC). METHODS: We performed a retrospective analysis of a prospectively maintained database and compared all emergency department (ED) encounters, acute stroke admissions (including TIA), and thrombectomy cases admitted in March 2017-2019 to patients admitted in March 2020 at a comprehensive stroke center. RESULTS: Number of total ED encounters (22%, p=0.005), acute ischemic strokes (40%, p=0.001), and TIAs (60%, p=0.163) decreased between March of 2017–2019 compared to March of 2020. The number of patients undergoing EVT in March 2020 was comparable to March 2017–2019 (p=0.430). CONCLUSION: A pandemic-related stay-at-home policy reduces the utilization of stroke emergency services at a CSC. This effect appears to be more prominent for ED encounters, all stroke admissions and TIAs, and less impactful for severe strokes. Given the relatively low prevalence of COVID-19 cases in our region, this decrement is likely related to healthcare seeking behavior rather than capacity saturation.


docid: ulohnddw

title: Case fatality rate and viral aetiologies of acute respiratory tract infections in HIV positive and negative people in Africa: The VARIAFRICA-HIV systematic review and meta-analysis

text: Abstract Background To set priorities for efficient control of acute respiratory tract infection (ARTI) in Africa, it is necessary to have accurate estimate of its burden, especially among HIV-infected populations. Objectives To compare case fatality rate (CFR) and viral aetiologies of ARTI between HIV-positive and HIV-negative populations in Africa. Study design We searched PubMed, EMBASE, Web of Knowledge, Africa Journal Online, and Global Index Medicus to identify studies published from January 2000 to April 2018. Random-effect meta-analysis method was used to assess association (pooled weighted odds ratios (OR) with 95% confidence interval (CI)). Results A total of 36 studies (126,526 participants) were included. CFR was significantly higher in patients with HIV than in HIV-negative controls (OR 4.10, 95%CI: 2.63–6.27, I²: 93.7%). The risk was significantly higher among children ≤5 years (OR 5.51, 95%CI 2.83–10.74) compared to people aged >5 years (OR 1.48, 95%CI 1.17–1.89); p = 0.0002. There was no difference between children (15 years) and adults and between regions of Africa. There was no difference for viral respiratory aetiologies (Enterovirus, Adenovirus, Bocavirus, Coronavirus, Metapneumovirus, Parainfluenza, Influenza, and Respiratory Syncytial Virus) of ARTI between HIV-positive and HIV-negative people, except for Rhinovirus where being HIV-negative was associated with Rhinovirus (OR 0.70; 95%CI 0.51–0.97, I²: 63.4%). Conclusions This study shows an increased risk of deaths among HIV-infected individuals with ARTI, however with no difference in viral aetiologies compared to HIV-negative individuals in Africa. ARTI deserves more attention from HIV health-care providers for efficient control. Specific strategies are needed for HIV-positive children under 5.


title: Inhomogeneity of epidemic spreading

text: In this study, we use the characteristic infected cluster size to investigate the inhomogeneity of the epidemic spreading in static and dynamic complex networks. The simulation results show that the epidemic spreads inhomogeneously in both cases. Also, the inhomogeneity of the epidemic spreading becomes smaller with increasing speed of moving individuals and almost disappears when the speed is high enough.


Is prevention better than a cure? A letter to the editor on “World Health Organization declares global emergency: A review of the 2019 novel coronavirus (COVID-19)”


docid: wkfgrssp

title: Ion flux in the lung: virus-induced inflammasome activation

text: Innate immunity has a primary role in lung antimicrobial defenses. The inflammasome has evolved for this purpose and is an important surveillance system that, when triggered, fights infection and eliminates pathogens. However, there is growing evidence that the inflammasome also plays a role in the pathogenesis of acute and chronic respiratory disease. Inflammasomes contribute to both the clearance of the pathogen as well as its pathogenesis – depending on the amount of inflammation triggered. How respiratory viruses trigger inflammasome activation remains unclear. Emerging evidence shows that ion flux is responsible for triggering inflammasome activation in the lung, causing lung pathology and disease exacerbations. Viroporins, encoded by all common respiratory viruses, are responsible for the changes in intracellular ion homeostasis that modulate inflammasome activation. This is a novel mechanism by which respiratory viral infection activates inflammasomes, and identifies sensing of disturbances in intracellular ionic concentrations as a novel pathogen-recognition pathway in the lung.


title: Identification of Plakortide E from the Caribbean Sponge Plakortis halichondroides as a Trypanocidal Protease Inhibitor using Bioactivity-Guided Fractionation

text: In this paper, we report new protease inhibitory activity of plakortide E towards cathepsins and cathepsin-like parasitic proteases. We further report on its anti-parasitic activity against Trypanosoma brucei with an IC(50) value of 5 μM and without cytotoxic effects against J774.1 macrophages at 100 μM concentration. Plakortide E was isolated from the sponge Plakortis halichondroides using enzyme assay-guided fractionation and identified by NMR spectroscopy and mass spectrometry. Furthermore, enzyme kinetic studies confirmed plakortide E as a non-competitive, slowly-binding, reversible inhibitor of rhodesain.


title: Macromolecular Antiviral Agents against Zika, Ebola, SARS, and Other Pathogenic Viruses

text: Viral pathogens continue to constitute a heavy burden on healthcare and socioeconomic systems. Efforts to create antiviral drugs repeatedly lag behind the advent of pathogens and growing understanding is that broad‐spectrum antiviral agents will make strongest impact in future antiviral efforts. This work performs selection of synthetic polymers as novel broadly active agents and demonstrates activity of these polymers against Zika, Ebola, Lassa, Lyssa, Rabies, Marburg, Ebola, influenza, herpes simplex, and human immunodeficiency viruses. Results presented herein offer structure–activity relationships for these pathogens in terms of their susceptibility to inhibition by polymers, and for polymers in terms of their anionic charge and hydrophobicity that make up broad‐spectrum antiviral agents. The identified leads cannot be predicted based on prior data on polymer‐based antivirals and represent promising candidates for further development as preventive microbicides.


title: Can pioglitazone be potentially useful therapeutically in treating patients with covid-19?

text: Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic disease (COVID-19) that has spread globally causing more than 30,000 deaths. Despite the immense and ongoing global effort, no efficacious drugs to fight this plague have been identified and patients admitted to the intensive care units (ICU), for respiratory distress, are managed mostly by means of supportive care based on oxygen maintenance. Several authors have reported that the prevalence of hypertension, diabetes, cardiovascular and cerebrovascular diseases comorbidities were indeed frequent among patients with COVID-19, which suggests that these conditions are likely to aggravate and complicate the prognosis. What the aforementioned diseases have in common is a latent chronic inflammatory state that may be associated with the alteration of laboratory parameters that are typical of the metabolic syndrome and insulin resistance. In severe COVID-19 patients laboratory markers of inflammation such as C-reactive protein, IL-6, D-dimer, serum ferritin and lactate dehydrogenase are elevated in many patients; assessed since the 4th-6th day of illness onset, such increases seem to be predictive of an adverse prognosis. Our hypothesis is that drugs belonging to the family of thiazolidinediones (TZD) such as pioglitazone or rosiglitazone, approved for treating the condition of insulin resistance and the accompanying inflammation, could ameliorate the prognosis of those COVID-19 patients with diabetes, hypertension and cardiovascular disorders comorbidities. TZD are PPARγ agonists that act on nuclear receptors, thereby triggering certain transcription factors. TZD were widely used for type-2 diabetes in the first decade of this century and although concerns have been raised for possible side effects associated with long-term treatment, their use has been recently revaluated for their anti-inflammatory properties in numerous medical conditions.


title: Emerging Biomolecular Testing to Assess the Risk of Mortality from COVID-19 Infection

text: [Image: see text] Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 and COVID-19) has produced an unprecedented global pandemic. Though the death rate from COVID-19 infection is ∼2%, many infected people recover at home. Among patients for whom COVID-19 is deadly are those with pre-existing comorbidities. Therefore, identification of populations at highest risk of COVID-19 mortality could significantly improve the capacity of healthcare providers to take early action and minimize the possibility of overwhelming care centers, which in turn would save many lives. Although several approaches have been used/developed (or are being developed/suggested) to diagnose COVID-19 infection, no approach is available/proposed for fast diagnosis of COVID-19 infections likely to be fatal. The central aim of this short perspective is to suggest a few possible nanobased technologies (i.e., protein corona sensor array and magnetic levitation) that could discriminate COVID-19-infected people while still in the early stages of infection who are at high risk of death. Such discrimination technologies would not only be useful in protecting health care centers from becoming overwhelmed but would also provide a powerful tool to better control possible future pandemics with a less social and economic burden.


Oncology clinical trials in the time of COVID-19: how a pandemic can revolutionize patients’ care


title: COVID-19 and Cancer: a Comprehensive Review

text: PURPOSE OF REVIEW: The outbreak of the novel coronavirus disease 2019 (COVID-19) has emerged to be the biggest global health threat worldwide, which has now infected over 1.7 million people and claimed more than 100,000 lives around the world. Under these unprecedented circumstances, there are no well-established guidelines for cancer patients. RECENT FINDINGS: The risk for serious disease and death in COVID-19 cases increases with advancing age and presence of comorbid health conditions. Since the emergence of the first case in Wuhan, China, in December 2019, tremendous research efforts have been underway to understand the mechanisms of infectivity and transmissibility of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a fatal virus responsible for abysmal survival outcomes. To minimize the mortality rate, it becomes prudent to identify symptoms promptly and employ treatments appropriately. Even though no cure has been established, multiple clinical trials are underway to determine the most optimal strategy. Managing cancer patients under these circumstances is rather challenging, given their vulnerable status and the aggressive nature of their underlying disease. SUMMARY: In this comprehensive review, we discuss the impact of COVID-19 on health and the immune system of those affected, reviewing the latest treatment approaches and ongoing clinical trials. Additionally, we discuss challenges faced while treating cancer patients and propose potential approaches to manage this vulnerable population during this pandemic.


title: Structural genomics of the SARS coronavirus: cloning, expression, crystallization and preliminary crystallographic study of the Nsp9 protein

text: The aetiologic agent of the recent epidemics of Severe Acute Respiratory Syndrome (SARS) is a positive‐stranded RNA virus (SARS‐CoV) belonging to the Coronaviridae family and its genome differs substantially from those of other known coronaviruses. SARS‐CoV is transmissible mainly by the respiratory route and to date there is no vaccine and no prophylactic or therapeutic treatments against this agent. A SARS‐CoV whole‐genome approach has been developed aimed at determining the crystal structure of all of its proteins or domains. These studies are expected to greatly facilitate drug design. The genomes of coronaviruses are between 27 and 31.5 kbp in length, the largest of the known RNA viruses, and encode 20–30 mature proteins. The functions of many of these polypeptides, including the Nsp9–Nsp10 replicase‐cleavage products, are still unknown. Here, the cloning, Escherichia coli expression, purification and crystallization of the SARS‐CoV Nsp9 protein, the first SARS‐CoV protein to be crystallized, are reported. Nsp9 crystals diffract to 2.8 Å resolution and belong to space group P6(1/5)22, with unit‐cell parameters a = b = 89.7, c = 136.7 Å. With two molecules in the asymmetric unit, the solvent content is 60% (V (M) = 3.1 Å(3) Da(−1)).


title: Risk of Bacterial Coinfections in Febrile Infants 60 Days Old and Younger with Documented Viral Infections

text: Objective To determine the risk of serious bacterial infections (SBIs) in young febrile infants with and without viral infections. Study design Planned secondary analyses of a prospective observational study of febrile infants 60 days of age or younger evaluated at 1 of 26 emergency departments who did not have clinical sepsis or an identifiable site of bacterial infection. We compared patient demographics, clinical, and laboratory findings, and prevalence of SBIs between virus-positive and virus-negative infants. Results Of the 4778 enrolled infants, 2945 (61.6%) had viral testing performed, of whom 1200 (48.1%) were virus positive; 44 of the 1200 had SBIs (3.7%; 95% CI, 2.7%-4.9%). Of the 1745 virus-negative infants, 222 had SBIs (12.7%; 95% CI, 11.2%-14.4%). Rates of specific SBIs in the virus-positive group vs the virus-negative group were: UTIs (33 of 1200 [2.8%; 95% CI, 1.9%-3.8%] vs 186 of 1745 [10.7%; 95% CI, 9.2%-12.2%]) and bacteremia (9 of 1199 [0.8%; 95% CI, 0.3%-1.4%] vs 50 of 1743 [2.9%; 95% CI, 2.1%-3.8%]). The rate of bacterial meningitis tended to be lower in the virus-positive group (0.4%) than in the viral-negative group (0.8%); the difference was not statistically significant. Negative viral status (aOR, 3.2; 95% CI, 2.3-4.6), was significantly associated with SBI in multivariable analysis. Conclusions Febrile infants ≤60 days of age with viral infections are at significantly lower, but non-negligible risk for SBIs, including bacteremia and bacterial meningitis.


title: Loop‐mediated isothermal amplification method for detection of human papillomavirus type 6, 11, 16, and 18

text: A new method was developed for detection of human papillomavirus (HPV) by loop‐mediated isothermal amplification (LAMP), which was compared with the polymerase chain reaction (PCR), and real‐time PCR for specificity and sensitivity. All initial validation studies with the control DNA proved to be type‐specific. In order to evaluate the reliability of HPV type‐specific LAMP detecting HPV DNA from clinical samples, tissue specimens were obtained from 27 patients with external genital polypoid lesions. The histologic diagnoses included condyloma acuminatum (n = 21), bowenoid papulosis (n = 2), seborrheic keratosis (n = 2), epidermolytic acanthoma (n = 1), and hairy nymphae (n = 1). HPV‐6 DNA and HPV‐11 DNA were detected in 18 and 3 of 21 condylomata acuminata, respectively, and there was no simultaneous infection. HPV‐16 DNA was detected in one of two bowenoid papuloses. HPV DNA was not detected in the seborrheic keratoses, epidermolytic acanthoma, and hairy nymphae. These results correlated perfectly with those from real‐time PCR analysis. Most positive samples contained high copy numbers of HPV DNA. HPV‐11 DNA was detected in one case that could not be detected by PCR. The average reaction time was about 59 min. There was a linear correlation between the genome quantity and reaction time to reach the threshold. The LAMP method has an additional advantage as a quantitative method, and is superior in terms of sensitivity, specificity, rapidity, and simplicity, and can potentially be a valuable tool for the detection of HPV DNA. J. Med. Virol. 79:605–615, 2007. © 2007 Wiley‐Liss, Inc.


Canadian Geriatrics in the Time of COVID‐19


title: Latent organizing for responding to emergencies: foundations for research

text: Time and again, many organizations and their staff members must respond to unexpected catastrophes like hurricanes (e.g., Katrina), virus pandemics (e.g., COVID-19), or other major emergencies. As a result, some organizations allow their employees to respond to external emergencies by engaging in response actions for a limited time, like in the case of emergency response teams. The latter teams consist of employees that act as emergency response officers who can respond to floods, train crashes, or other emergencies. Emergency response teams constitute an example of so-called latent organizing (LO) in the preparation for and response to any (unpredictable) future emergency. While latent organizing is ubiquitous in a societal and professional sense, it has hardly been studied in the organization design literature. In this paper, we develop a research agenda for studying LO. LO serves to prepare for and respond to emergencies, but otherwise remains largely dormant and inactive. When it is inactive, host organizations use the LO’s human and other resources for their own gainful purposes. Resources for LO are thus organized in a quasi-permanent fashion, one that is rather latent until activated by an emergency. We further develop the construct of latency to explore how effective LO can be designed and facilitated. In addition, we develop a research agenda for future work in this area.


title: Biological and phylogenetic characterization of a novel hemagglutination‐negative avian avulavirus 6 isolated from wild waterfowl in China

text: Up to now only nine whole genome sequences of avian avulavirus 6 (AAvV‐6) had been documented in the world since the first discovery of AAvV‐6 (AAvV‐6/duck/HongKong/18/199/77) at a domestic duck in 1977 from Hong Kong of China. Very limited information is known about the regularities of transmission, genetic and biological characteristics of AAvV‐6 because of the lower isolation rate and mild losses for poultry industry. To better further explore the relationships among above factors, an AAvV‐6 epidemiological surveillance of domestic poultry and wild birds in six provinces of China suspected of sites of inter‐species transmission and being intercontinental flyways during the year 2013–2017 was conducted. Therefore, 9,872 faecal samples from wild birds and 1,642 cloacal and tracheal swab samples from clinically healthy poultry of live bird market (LBM) were collected respectively. However, only one novel hemagglutination‐negative AAvV‐6 isolate (AAvV‐6/mallard/Hubei/2015) was isolated from a fresh faecal sample obtained from mallard at a wetland of Hubei province. Sequencing and phylogenetic analyses of this AAvV‐6 isolate (AAvV‐6/mallard/Hubei/2015) indicated that this isolate grouping to genotype I were epidemiological intercontinentally linked with viruses from the wild birds in Europe and America. Meanwhile, at least two genotypes (I and II) are existed within serotype AAvV‐6. In additional, this novel hemagglutination‐negative AAvV‐6 isolate in chicken embryos restored its hemagglutination when pre‐treated with trypsin. These findings, together with data from other AAvV‐6, suggest potential epidemiological intercontinental spreads among AAvV‐6 transmission by wild migratory birds, and reveal potential threats to wild birds and domestic poultry worldwide.


title: Characteristics and Clinical Outcomes of COVID‐19 Patients in an Underserved‐Inner City Population: A Single Tertiary Center Cohort

text: BACKGROUND: There is limited information describing the characteristics and clinical outcomes of patients infected with coronavirus disease 2019 (COVID‐19) especially those in underserved urban area with minority population in the United States. METHODS: This is a retrospective single center study for patients who were admitted with COVID‐19 infection. Data collection was from March 1 through April 24,2020. Demographic, clinical, laboratory, and treatment data were presented using descriptive statistics and frequencies. Chi‐square test and multivariate logistic regression were used to determine association of risk factors and clinical outcomes. RESULTS: A total of 242 inpatients were included with a mean age of 66 ±14.75 (±SD). 50% were female and 70% were African American. Comorbidities included hypertension (74%), diabetes mellitus (49%), and 19% had either COPD or asthma. Older age was associated with higher risk of inpatient death OR 1.056 [95% CI 1.023 to 1.090; p=0.001]. Inpatient mortality occurred in 70% who needed mechanical ventilation (OR: 29.51; 95% CI: 13.28‐65.60; p<0.0001), 58% who required continuous renal replacement therapy/hemodialysis (CRRT/HD) (OR: 6.63; 95% CI: 2.74‐16.05; p<0.0001), and 69% who needed vasopressors (OR: 30.64; 95% CI: 13.56 to 69.20; p<0.0001). Amongst biomarkers of disease severity, only baseline CRP levels (145±116 mg/L) were associated with mortality OR 1.008 [95% CI 1.003 to 1.012; p=0.002]. CONCLUSION: Majority of hospitalized patients had hypertension and diabetes. Older age was an independent risk factor for inpatient mortality. Requirement of mechanical ventilation, vasopressor use, and CRRT/HD were associated significantly with inpatient mortality. Higher baseline CRP was significantly associated with inpatient death. This article is protected by copyright. All rights reserved.


title: Corona-Krise: Was zeigt sich in der Herstellung und Bewältigung eines Ausnahmezustandes über die Möglichkeiten und Formen gesellschaftlicher Problembearbeitung?

text: Der Beitrag setzt sich mit der Frage auseinander, was den gesellschaftlichen Reaktionen auf die Ausbreitung des Coronavirus zu Grunde liegt. In einer sozialwissenschaftlichen Perspektive wird argumentiert, dass diese nicht zureichend als zwangsläufige politische Konsequenz aus Einsichten der medizinischen Virenforschung verstanden werden können, sondern auch als Folge einer fundamentalen kulturellen Verunsicherung in den Blick zu nehmen sind. Aufgezeigt wird zudem die nationalistische Rahmung der politischen Reaktionen. Abschließend wird darauf auf die Gefahr hingewiesen, dass das, was in einem deklarierten temporären Ausnahmezustand gesellschaftlich durchsetzbar ist, auch unter anderen Bedingungen aktualisiert werden könnte.