title: The Predictive Capacity of Air Travel Patterns during the Global Spread of the COVID-19 Pandemic: Risk, Uncertainty and Randomness

text: Air travel has a decisive role in the spread of infectious diseases at the global level. We present a methodology applied during the early stages of the COVID-19 pandemic that uses detailed aviation data at the final destination level in order to measure the risk of the disease spreading outside China. The approach proved to be successful in terms of identifying countries with a high risk of infected travellers and as a tool to monitor the evolution of the pandemic in different countries. The high number of undetected or asymptomatic cases of COVID-19, however, limits the capacity of the approach to model the full dynamics. As a result, the risk for countries with a low number of passengers from Hubei province appeared as low. Globalization and international aviation connectivity allow travel times that are much shorter than the incubation period of infectious diseases, a fact that raises the question of how to react in a potential new pandemic.


title: Influenza Pandemics in Singapore, a Tropical, Globally Connected City

text: Tropical cities such as Singapore do not have well-defined influenza seasons but have not been spared from influenza pandemics. The 1918 epidemic in Singapore, which was then already a major global trading hub, occurred in 2 waves, June–July, and October–November, and resulted in >2,870 deaths. The excess mortality rate was higher than that for industrialized nations in the Northern Hemisphere but lower than that for less industrialized countries in Asia and Africa. The 1957 epidemic occurred in May and resulted in widespread illness. The 1968 epidemic occurred in August and lasted a few weeks, again with widespread illness. Tropical cities may be affected early in a pandemic and have higher mortality rates. With the increase in travel and trade, a future pandemic may reach a globally connected city early and spread worldwide. Preparedness and surveillance plans must be developed to include the megacities of the tropical world.


title: Molecular pathogenesis of virus infections

text: Although a very wide range of viral diseases exists in vertebrates, certain generalizations can be made regarding pathogenetic pathways on the molecular level. The presentation will focus on interactions of virions and their components with target cells. Using coronaviruses as examples the changes in virulence have been traced back to single mutational events; recombination, however, is likely to be an alternative mechanism by which virus-host interactions (e.g. the cell-, organ- or animal species-spectrum) can dramatically change. Receptor molecules are essential for the early interactions during infection and some ot these have been identified. Events in the target cell and the host organism are discussed, and wherever possible, aspects of virus evolution and cooperation between infectious agents are highlighted.


title: Human microRNA‐30 inhibits influenza virus infection by suppressing the expression of SOCS1, SOCS3, and NEDD4

text: Influenza A virus (IAV) has evolved multiple mechanisms to compromise type I interferon (IFN) responses. The antiviral function of IFN is mainly exerted by activating the JAK/STAT signalling and subsequently inducing IFN‐stimulated gene (ISG) production. However, the mechanism by which IAV combat the type I IFN signalling pathway is not fully elucidated. In this study, we explored the roles of human microRNAs modulated by IAV infection in type I IFN responses. We demonstrated that microRNA‐30 (miR‐30) family members were downregulated by IAV infection. Our data showed that the forced expression of miR‐30 family members inhibited IAV proliferation, while miR‐30 family member inhibitors promoted IAV proliferation. Mechanistically, we found that miR‐30 family members targeted and reduced SOCS1 and SOCS3 expression, and thus relieved their inhibiting effects on IFN/JAK/STAT signalling pathway. In addition, miR‐30 family members inhibited the expression of NEDD4, a negative regulator of IFITM3, which is important for host defence against influenza viruses. Our findings suggest that IAV utilises a novel strategy to restrain host type I IFN‐mediated antiviral immune responses by decreasing the expression of miR‐30 family members, and add a new way to understand the mechanism of immune escape caused by influenza viruses.


title: Community-acquired pneumonia and Gram-negative bacilli in Cambodia—incidence, risk factors and clinical characteristics

text: BACKGROUND: In Western settings, community-acquired pneumonia (CAP) due to Gram-negative bacilli (GNB) is relatively rare. Previous studies from Asia, however, indicate a higher prevalence of GNB in CAP, but data, particularly from Southeast Asia, are limited. METHODS: This is a prospective observational study of 1451 patients ≥15 y of age with CAP from two hospitals in Cambodia between 2007 and 2010. The proportion of GNB was estimated. Risk factors and clinical characteristics of CAP due to GNB were assessed using logistic regression models. RESULTS: The prevalence of GNB was 8.6% in all CAP patients and 15.8% among those with a valid respiratory sample. GNB infection was independently associated with diabetes, higher leucocyte count and CAP severity. Mortality was higher in patients with CAP due to GNB. CONCLUSIONS: We found a high proportion of GNB in a population hospitalized for CAP in Cambodia. Given the complex antimicrobial sensitivity patterns of certain GNBs and the rapid emergence of multidrug-resistant GNB, microbiological laboratory capacity should be strengthened and prospective clinical trials comparing empiric treatment algorithms according to the severity of CAP are needed.


title: Type 2 and interferon inflammation strongly regulate SARS-CoV-2 related gene expression in the airway epithelium

text: Coronavirus disease 2019 (COVID-19) outcomes vary from asymptomatic infection to death. This disparity may reflect different airway levels of the SARS-CoV-2 receptor, ACE2, and the spike protein activator, TMPRSS2. Here we explore the role of genetics and co-expression networks in regulating these genes in the airway, through the analysis of nasal airway transcriptome data from 695 children. We identify expression quantitative trait loci (eQTL) for both ACE2 and TMPRSS2, that vary in frequency across world populations. Importantly, we find TMPRSS2 is part of a mucus secretory network, highly upregulated by T2 inflammation through the action of interleukin-13, and that interferon response to respiratory viruses highly upregulates ACE2 expression. Finally, we define airway responses to coronavirus infections in children, finding that these infections upregulate IL6 while also stimulating a more pronounced cytotoxic immune response relative to other respiratory viruses. Our results reveal mechanisms likely influencing SARS-CoV-2 infectivity and COVID-19 clinical outcomes.


title: Detection of avian rotaviruses of groups A, D, F and G in diseased chickens and turkeys from Europe and Bangladesh

text: Abstract Avian rotaviruses (AvRVs) represent a diverse group of intestinal viruses, which are suspected as the cause of several diseases in poultry with symptoms of diarrhoea, growth retardation or runting and stunting syndrome (RSS). To assess the distribution of AvRVs in chickens and turkeys, we have developed specific PCR protocols. These protocols were applied in two field studies investigating faecal samples or intestinal contents of diseased birds derived from several European countries and Bangladesh. In the first study, samples of 166 chickens and 33 turkeys collected between 2005 and 2008 were tested by PAGE and conventional RT-PCR and AvRVs were detected in 46.2%. In detail, 16.1% and 39.2% were positive for AvRVs of groups A or D, respectively. 11.1% of the samples contained both of them and only four samples (2.0%) contained rotaviruses showing a PAGE pattern typical for groups F and G. In the second study, samples from 375 chickens and 18 turkeys collected between 2009 and 2010 were analyzed using a more sensitive group A-specific and a new group D-specific real-time RT-PCR. In this survey, 85.0% were AvRV-positive, 58.8% for group A AvRVs, 65.9% for group D AvRVs and 38.9% for both of them. Although geographical differences exist, the results generally indicate a very high prevalence of group A and D rotaviruses in chicken and turkey flocks with cases of diarrhoea, growth retardation or RSS. The newly developed diagnostic tools will help to investigate the epidemiology and clinical significance of AvRV infections in poultry.


title: Proteomic analysis of ovomucoid hypersensitivity in mice by two-dimensional difference gel electrophoresis (2D-DIGE)

text: There is a need to develop reliable methods to assess the safety of genetically modified and other novel foods. The aim of this study was to identify protein biomarkers of food allergy in mice exposed to ovomucoid (OVM), a major food allergen found in chicken egg white. BALB/c mice were repeatedly sensitized by gavage with OVM and cholera toxin (CT) and control mice were exposed to a mixture of amino acids with CT. At the endpoint, all mice were challenged intraperitoneally with OVM and alum. Type-1 hypersensitivity was confirmed in OVM-sensitized mice by observation of clinical signs of anaphylaxis and elevated levels of plasma histamine, OVM-specific IgE and OVM-specific IgG by ELISA. Differential protein expression was assessed in albumin-depleted plasma as well as in mesenteric lymph node, liver, spleen, and ileum by two-dimensional difference gel electrophoresis (2D-DIGE). Differentially expressed proteins were identified by liquid chromatography with tandem mass spectrometry. Plasma proteins overexpressed in OVM-sensitized mice included haptoglobin (41-fold), serum amyloid A (19-fold) and peroxiredoxin-2 (1.9-fold). Further validation of these plasma proteins in other animal models of food allergy with different food allergens is required to assess their potential as candidate biomarkers for use in evaluating the allergenicity of novel foods.


title: Monocytic angiotensin-converting enzyme 2 relates to atherosclerosis in patients with chronic kidney disease

text: Background: Increased levels of monocytic angiotensin-converting enzyme (ACE) found in haemodialysis (HD) patients may directly participate in the pathogenesis of atherosclerosis. We demonstrated recently that uremia triggers the development of highly pro-atherogenic monocytes via an angiotensin II (AngII)–dependent mechanism. Opposing actions of the AngII-degrading ACE2 remain largely unknown. We examined the status of both ACEs and related receptors in circulating leukocytes of HD, not-dialyzed CKD and healthy individuals. Furthermore, we tested the possible impact of monocytic ACEs on atherogenesis and behaviour of the cells under conditions mimicking chronic renal failure. Methods: Expression of ACE, ACE2, AT1R, AT2R and MASR was investigated on circulating leukocytes from 71 HD (62 ± 14 years), 24 CKD stage 3–5 (74 ± 10 years) patients and 37 healthy control subjects (53 ± 6 years) and isolated healthy monocytes treated with normal and uremic serum. Analyses of ACE, ACE2, ICAM-1, VCAM-1, MCSF and endothelial adhesion were tested on ACE-overexpressing THP-1 monocytes treated with captopril or losartan. ACE2-overexpressing monocytes were subjected to transmigration and adhesion assays and investigated for MCP-1, ICAM-1, VCAM-1, MCSF, AT1R and AT2R expression. Results: The ACE mRNA level was significantly increased in HD and CKD stage 3–5 leukocytes. Correspondingly, ACE2 was downregulated and AngII as well as MAS receptor expression was upregulated in these cells. Healthy monocytes preconditioned with uremic serum reflected the same expressional regulation of ACE/ACE2, MAS and AngII receptors as those observed in HD and CKD stage 3–5 leukocytes. Overexpression of monocytic ACE dramatically decreased levels of ACE2 and induced a pro-atherogenic phenotype, partly reversed by AngII-modifying treatments, leading to an increase in ACE2. Overexpression of ACE2 in monocytes led to reduced endothelial adhesion, transmigration and downregulation of adhesion-related molecules. Conclusions: HD and not-dialyzed CKD stage 3–5 patients show enhanced ACE and decreased ACE2 expression on monocytes. This constellation renders the cells endothelial adhesive and likely supports the development of atherosclerosis.


title: Weekly Monitoring of Children with Asthma for Infections and Illness During Common Cold Seasons

text: BACKGROUND: Exacerbations of childhood asthma and rhinovirus infections both peak during the spring and fall, suggesting that viral infections are major contributors to seasonal asthma morbidity. OBJECTIVES: To evaluate rhinovirus infections during peak seasons in children with asthma, and to analyze relationships between viral infection and illness severity. METHODS: Fifty-eight children with asthma ages 6-8 years provided 5 consecutive weekly nasal lavage samples during September and April; symptoms, medication use, and peak flow were recorded. Rhinoviruses were identified using multiplex PCR and partial sequencing of viral genomes. RESULTS: Viruses were detected in 36-50% of the specimens, and, 72-99% of the viruses were rhinoviruses. There were 52 different strains (including 16 HRV-C) among the 169 rhinovirus isolates; no strains found in more than two collection periods, and all but two children had a respiratory infection. Virus-positive weeks were associated with greater cold and asthma severity (p<0.0001 and p=0.0002 respectively). Furthermore, virus-positive illnesses had increased duration and severity of cold and asthma symptoms, and more frequent loss of asthma control (47% vs. 22%, p=0.008). While allergen-sensitized vs. non-sensitized children had the same number of viral infections, the former had 47% more symptomatic viral illnesses (1.19 vs. 0.81 per month, p=0.03). CONCLUSIONS: Rhinovirus infections are nearly universal in children with asthma during common cold seasons, likely due to a plethora of new strains appearing each season. Illnesses associated with viruses have greater duration and severity. Finally, atopic asthmatic children experienced more frequent and severe viral-induced illnesses. CLINICAL IMPLICATIONS: The combination of viral infection and allergy increases the morbidity of respiratory illness in children with asthma.


title: Development and Evaluation of a SYBR Green-Based Real Time RT-PCR Assay for Detection of the Emerging Avian Influenza A (H7N9) Virus

text: Most recently a novel avian-origin influenza A (H7N9) virus emerged in China and has been associated with lots of human infection and fatal cases. Genetic analysis of the viral genome revealed that this reassortant virus might be better adapted to humans than other avian influenza viruses. Molecular diagnostic methods are thus urgently needed in public health laboratories. In this study, a SYBR green-based one-step real time reverse transcription-PCR (RT-PCR) was developed to detect the novel H7N9 virus. The primer pairs on the basis of the hemagglutinin and neuraminidase gene sequences of H7N9 viruses amplified subtype-specific fragments with Tm values of 80.77±0.06°C for H7 and 81.20±0.17°C for N9 respectively. The standard curves showed a dynamic linear range across 6 log units of RNA copy number (10(6) to 10(1) copies/ µl) with a detection limit of 10 copies per reaction for both H7 and N9 assays by using serial ten-fold diluted in-vitro transcribed viral RNA. In addition, no cross-reactivity was observed with seasonal H1N1, H1N1 pdm09, H3N2, H5N1 and H9N2 viruses as well as other human respiratory viruses. When the assay was further evaluated in H7N9 virus infected clinical samples, positive amplification signals were obtained in all of the specimens with the accordance between H7 and N9 assays. Therefore, the established SYBR green-based real time RT-PCR assay could provide a rapid, sensitive, specific and reliable alternative approach with lower costs for high throughput screening of suspected samples from humans, animals and environments in first line public health laboratories.


title: Social distancing measures to control the COVID-19 pandemic: potential impacts and challenges in Brazil.

text: The COVID-19 pandemic has challenged researchers and policy makers to identify public safety measures forpreventing the collapse of healthcare systems and reducingdeaths. This narrative review summarizes the available evidence on the impact of social distancing measures on the epidemic and discusses the implementation of these measures in Brazil. Articles on the effect of social distancing on COVID-19 were selected from the PubMed, medRXiv and bioRvix databases. Federal and state legislation was analyzed to summarize the strategies implemented in Brazil. Social distancing measures adopted by the population appear effective, particularly when implemented in conjunction with the isolation of cases and quarantining of contacts. Therefore, social distancing measures, and social protection policies to guarantee the sustainability of these measures, should be implemented. To control COVID-19 in Brazil, it is also crucial that epidemiological monitoring is strengthened at all three levels of the Brazilian National Health System (SUS). This includes evaluating and usingsupplementary indicators to monitor the progression of the pandemic and the effect of the control measures, increasing testing capacity, and making disaggregated notificationsand testing resultstransparentand broadly available.


Hematologic parameters in patients with COVID‐19 infection: a reply


title: Toll‐like receptor‐2 exacerbates murine acute viral hepatitis

text: Viral replication in the liver is generally detected by cellular endosomal Toll‐like receptors (TLRs) and cytosolic helicase sensors that trigger antiviral inflammatory responses. Recent evidence suggests that surface TLR2 may also contribute to viral detection through recognition of viral coat proteins but its role in the outcome of acute viral infection remains elusive. In this study, we examined in vivo the role of TLR2 in acute infections induced by the highly hepatotrophic mouse hepatitis virus (MHV) type 3 and weakly hepatotrophic MHV‐A59 serotype. To address this, C57BL/6 (wild‐type; WT) and TLR2 knockout (KO) groups of mice were intraperitoneally infected with MHV3 or MHV‐A59. MHV3 infection provoked a fulminant hepatitis in WT mice, characterized by early mortality and high alanine and aspartate transaminase levels, histopathological lesions and viral replication whereas infection of TLR2 KO mice was markedly less severe. MHV‐A59 provoked a comparable mild and subclinical hepatitis in WT and TLR2 KO mice. MHV3‐induced fulminant hepatitis in WT mice correlated with higher hepatic expression of interferon‐β, interleukin‐6, tumour necrosis factor‐α, CXCL1, CCL2, CXCL10 and alarmin (interleukin‐33) than in MHV‐A59‐infected WT mice and in MHV3‐infected TLR2 KO mice. Intrahepatic recruited neutrophils, natural killer cells, natural killer T cells or macrophages rapidly decreased in MHV3‐infected WT mice whereas they were sustained in MHV‐A59‐infected WT mice and MHV3‐infected TLR2 KO. MHV3 in vitro infection of macrophagic cells induced rapid and higher viral replication and/or interleukin‐6 induction in comparison to MHV‐A59, and depended on viral activation of TLR2 and p38 mitogen‐activated protein kinase. Taken together, these results support a new aggravating inflammatory role for TLR2 in MHV3‐induced acute fulminant hepatitis.


title: Immunogenic properties of Landrace pigs selected for resistance to mycoplasma pneumonia of swine

text: Mycoplasma pneumonia of swine (MPS) lung lesions and immunogenic properties were compared between a Landrace line that was genetically selected for reduced incidence of pulmonary MPS lesions, and a non‐selected Landrace line. The MPS‐selected Landrace line showed significantly lower degrees of pulmonary MPS lesions compared with the non‐selected Landrace line. When changes in immunity before and after vaccination were compared, the percentage of B cells in the peripheral blood of the MPS‐selected Landrace line was significantly lower than that of the non‐selected line. Furthermore, the concentration of growth hormone and the mitogen activity of peripheral blood mononuclear cells in the MPS‐selected Landrace line showed significantly (P < 0.05) lower increases after vaccination than the non‐selected line. Conversely, the concentration of peripheral blood interferon (IFN)‐γ and salivary immunoglobulin A (IgA) after Mycoplasma hyopneumoniae vaccination was significantly higher in the MPS‐selected Landrace line than in the non‐selected line. Gene expression of toll‐like receptor (TLR)2 and TLR4 was significantly higher in the MPS‐selected Landrace line in immune tissues, with the exception of the hilar lymph nodes. The present results suggest that peripheral blood IFN‐γ, salivary IgA TLR2, and TLR4 are important immunological factors influencing the development of MPS lesions.


title: Transcriptional and Translational Landscape of Equine Torovirus

text: The genus Torovirus (subfamily Torovirinae, family Coronaviridae, order Nidovirales) encompasses a range of species that infect domestic ungulates, including cattle, sheep, goats, pigs, and horses, causing an acute self-limiting gastroenteritis. Using the prototype species equine torovirus (EToV), we performed parallel RNA sequencing (RNA-seq) and ribosome profiling (Ribo-seq) to analyze the relative expression levels of the known torovirus proteins and transcripts, chimeric sequences produced via discontinuous RNA synthesis (a characteristic of the nidovirus replication cycle), and changes in host transcription and translation as a result of EToV infection. RNA sequencing confirmed that EToV utilizes a unique combination of discontinuous and nondiscontinuous RNA synthesis to produce its subgenomic RNAs (sgRNAs); indeed, we identified transcripts arising from both mechanisms that would result in sgRNAs encoding the nucleocapsid. Our ribosome profiling analysis revealed that ribosomes efficiently translate two novel CUG-initiated open reading frames (ORFs), located within the so-called 5′ untranslated region. We have termed the resulting proteins U1 and U2. Comparative genomic analysis confirmed that these ORFs are conserved across all available torovirus sequences, and the inferred amino acid sequences are subject to purifying selection, indicating that U1 and U2 are functionally relevant. This study provides the first high-resolution analysis of transcription and translation in this neglected group of livestock pathogens. IMPORTANCE Toroviruses infect cattle, goats, pigs, and horses worldwide and can cause gastrointestinal disease. There is no treatment or vaccine, and their ability to spill over into humans has not been assessed. These viruses are related to important human pathogens, including severe acute respiratory syndrome (SARS) coronavirus, and they share some common features; however, the mechanism that they use to produce sgRNA molecules differs. Here, we performed deep sequencing to determine how equine torovirus produces sgRNAs. In doing so, we also identified two previously unknown open reading frames “hidden” within the genome. Together these results highlight the similarities and differences between this domestic animal virus and related pathogens of humans and livestock.


title: Will the COVID-19 pandemic worsen the obesity epidemic?

text: The sudden outbreak and global spread of COVID-19 represents one of the most profound societal and public health challenges in modern times. In this Comment, we call attention to the possibility that the societal strategies implemented to oppose COVID-19 might have long-term, negative effects on the obesity epidemic.


Bone Marrow Transplant Society of Australia and New Zealand COVID‐19 consensus position statement


Lack of seasonal variation of Middle East Respiratory Syndrome Coronavirus (MERS-CoV)


title: Protection of Mice Against Lethal Rabies Virus Challenge Using Short Interfering RNAs (siRNAs) Delivered Through Lentiviral Vector

text: The antiviral potential of small interfering RNAs (siRNAs) targeting rabies virus (RV) polymerase (L) and nucleoprotein (N) genes delivered through lentiviral vector was investigated. For in vitro evaluation, siRNAs expressing BHK-21 cell lines (BHK-L and BHK-N) were developed using transduction with Lenti-L and Lenti-N lentiviruses encoding siRNAs against RV-L and N genes, respectively. When these cell lines were challenged in vitro with RV Pasteur virus-11 (PV-11) strain, there was reduction in number of RV-specific foci and target gene transcripts indicating inhibitory effect on RV multiplication. For in vivo evaluation, mice were treated intracerebrally with lentiviruses and challenged with 20 LD(50) of RV challenge virus standard-11 (CVS-11) strain by intramuscular route in masseter muscle. Five out of eight mice treated with Lenti-N survived indicating 62.5 % protection. The control and Lenti-L-treated mice died within 7–10 days indicating lethal nature of challenge virus and no protection. These results demonstrated that siRNA targeting RV-N could not only inhibit RV multiplication, but also conferred protection in mice against lethal RV challenge. These findings have implication on therapeutic use of siRNA targeting RV-N against RV infection.


title: Olfactory and Gustatory Outcomes in COVID-19: A Prospective Evaluation in Nonhospitalized Subjects

text: OBJECTIVE: To prospectively assess the rate and timing of recovery of olfactory (OD) and gustatory (GD) dysfunction in patients affected by COVID-19. STUDY DESIGN: Cohort study. SETTING: Population-based evaluation in a COVID-19 high-prevalence region. SUBJECTS AND METHODS: We analyzed the clinical course of OD and GD in a cohort of home-quarantined SARS-CoV-2–positive patients from Northern Italy. Physicians administered a survey-based questionnaire at recruitment (T0). During follow-up, patients responded to online dedicated surveys modulated according to symptoms at T0. RESULTS: A total of 151 patients completed the follow-up survey. OD and/or GD were observed in 83% and 89% of subjects, respectively. Resolution rates of OD and GD at 30 days from onset were 87% and 82%, respectively. Risk factors for late resolution were grade of dysfunction at onset (total vs partial), gender, and presence of nasal congestion. Three (2%) patients previously reporting complete resolution of symptoms complained of subsequent recurrence of OD and/or GD after a mean of 19 days from resolution of the previous episode. CONCLUSION: COVID-19–related OD and GD had high rate of resolution in the first month from onset of symptoms. However, in 10% to 15% of patients, these symptoms showed only partial improvement after this period.


title: Clinical and histological characterization of vesicular COVID‐19 rashes: A prospective study in a tertiary care hospital

text: Vesicular skin rashes have been associated to the Coronavirus Disease 2019 (COVID‐19), but there is little information about this cutaneous manifestation. We designed a prospective observational study of patients diagnosed with COVID‐19 and vesicular lesions. Clinical characterization of skin findings was conducted by dermatologists. When possible, histological analysis and detection of severe acute respiratory coronavirus 2 (SARS‐CoV‐2) in the content of the vesicles was performed. A total of 24 patients were included. A disseminated pattern was found in 18 patients (75%), and a localized pattern was found in 6 patients (25%). The median duration of the skin rash was of 10 days. Out of all, 19 patients (79.2%) presented the skin rash after the onset of COVID‐19 symptoms. Histologic examination in two patients was consistent with viral infection, SARS‐CoV‐2 was not detected in four patients. This monocentric study shows the clinical characteristics of vesicular skin rashes in COVID‐19 patients.


title: Comparison of In Vitro Inactivation of SARS CoV‐2 with Hydrogen Peroxide and Povidone‐Iodine Oral Antiseptic Rinses

text: PURPOSE: To evaluate the in vitro inactivation of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) with hydrogen peroxide (H(2)O(2)) and povidone‐iodine (PVP‐I) oral antiseptic rinses at clinically recommended concentrations and contact times. MATERIALS AND METHODS: SARS‐CoV‐2, USA‐WA1/2020 strain virus stock was prepared prior to testing by growing in Vero 76 cells. The culture media for prepared virus stock was minimum essential medium (MEM) with 2% fetal bovine serum (FBS) and 50 μg/mL gentamicin. Test compounds consisting of PVP‐I oral rinse solutions and H(2)O(2) aqueous solutions were mixed directly with the virus solution so that the final concentration was 50% of the test compound and 50% of the virus solution. Thus PVP‐I was tested at concentrations of 0.5%, 1.25% and 1.5%, and H(2)O(2) was tested at 3% and 1.5% concentrations to represent clinically recommended concentrations. Ethanol and water were evaluated in parallel as standard positive and negative controls. All samples were tested at contact periods of 15 seconds and 30 seconds. Surviving virus from each sample was then quantified by standard end‐point dilution assay and the log reduction value of each compound compared to the negative control was calculated. RESULTS: After the 15‐second and 30‐second contact times, PVP‐I oral antiseptic rinse at all 3 concentrations of 0.5%, 1.25% and 1.5% completely inactivated SARS‐CoV‐2. The H(2)O(2) solutions at concentrations of 1.5% and 3.0% showed minimal viricidal activity after 15 seconds and 30 seconds of contact time. CONCLUSIONS: SARS‐CoV‐2 virus was completely inactivated by PVP‐I oral antiseptic rinse in vitro, at the lowest concentration of 0.5 % and at the lowest contact time of 15 seconds. Hydrogen peroxide at the recommended oral rinse concentrations of 1.5% and 3.0% was minimally effective as a viricidal agent after contact times as long as 30 seconds. Therefore, preprocedural rinsing with diluted PVP‐I in the range of 0.5% to 1.5% may be preferred over hydrogen peroxide during the COVID‐19 pandemic. This article is protected by copyright. All rights reserved


title: Outbreak analytics: a developing data science for informing the response to emerging pathogens

text: Despite continued efforts to improve health systems worldwide, emerging pathogen epidemics remain a major public health concern. Effective response to such outbreaks relies on timely intervention, ideally informed by all available sources of data. The collection, visualization and analysis of outbreak data are becoming increasingly complex, owing to the diversity in types of data, questions and available methods to address them. Recent advances have led to the rise of outbreak analytics, an emerging data science focused on the technological and methodological aspects of the outbreak data pipeline, from collection to analysis, modelling and reporting to inform outbreak response. In this article, we assess the current state of the field. After laying out the context of outbreak response, we critically review the most common analytics components, their inter-dependencies, data requirements and the type of information they can provide to inform operations in real time. We discuss some challenges and opportunities and conclude on the potential role of outbreak analytics for improving our understanding of, and response to outbreaks of emerging pathogens. This article is part of the theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control‘. This theme issue is linked with the earlier issue ‘Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes’.


title: Compartir los recursos útiles para la investigación: datos abiertos (open data)

text: Resumen Los datos abiertos (open data) son datos que pueden ser utilizados, reutilizados y redistribuidos libremente por cualquier persona, y que se encuentran sujetos, cuando más, al requerimiento de atribución y de compartirse de la misma manera en que aparecen. En este trabajo se describe el concepto de datos abiertos y de datos de investigación y por qué es necesario compartirlos. Se exponen las ventajas e inconvenientes de compartir datos y el procedimiento para llevar a cabo esta práctica. Se especifican los elementos que deben constituir el plan de gestión de los datos o documento que describe el tratamiento que van a recibir los datos de investigación recopilados o generados en el curso de un estudio o proyecto. Por último, se exponen las vías verde y dorada para la publicación de los datos y la necesidad de poner al servicio de los investigadores el asesoramiento técnico y las infraestructuras necesarias para que puedan llevar a cabo estas prácticas. Abstract Open data are data that can be freely used, reused and redistributed by any person, and that are, at most, subject to the attribution requirement and shared in the same way in which they appear. This paper describes the concept of open data and research data and why it is important to share them. The advantages and disadvantages of data sharing and the procedure for carrying out this practice are discussed. We specifies the elements that should constitute the data management plan or document that describes the treatment that will receive the research data collected or generated in the course of a study or project. Finally, the green and gold routes for the publication of the data and the need to put at the service of the researchers the technical advice and the infrastructures necessary to carry out these practices are presented.


title: MERS Coronavirus: An Emerging Zoonotic Virus

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging virus that was first reported in humans in June 2012 [...].


title: Seroprevalence of Dirofilaria immitis in Cats from Liaoning Province, Northeastern China

text: The present study was performed to investigate the seroprevalence and risk factors for Dirofilaria immitis infection in cats from Liaoning province, northeastern China. From October 2014 to September 2016, sera of 651 cats, including 364 domestic cats and 287 feral cats (332 females and 319 males) were assessed. They were tested for the presence of D. immitis antigen using SNAP Heartworm RT test kit. In this population, the average prevalence was 4.5%. Age and rearing conditions (feral or domestic) were found to be associated with the prevalence of D. immitis. The prevalence was significantly higher in feral cats compared with domestic cats (8.4% vs 1.4%, P<0.01). There was no significant difference between males and females (4.7% vs 4.2%, P>0.05), but older cats (≥3 years old) showed a statistically higher prevalence compared with younger cats (<3 years old) in feral populations (16.8 vs 2.4%, P<0.01), while the difference between the age groups was not statistically significant in domestic cats (2.4% vs 0.51%, P>0.05), all these results suggest that outdoor exposure time may be one of the most important factors for D. immitis prevalence in cats. Results reveal that D. immitis are prevalence in domestic and feral cats in northeastern China, which indicates that appropriate preventive measures should be taken to decrease the incidence of feline heartworm disease in Liaoning province, northeastern China.


Radiation for Glioblastoma in the Era of COVID-19: Patient Selection and Hypofractionation to Maximize Benefit and Minimize Risk


title: Rapid identification of inhibitors that interfere with poliovirus replication using a cell-based assay

text: Abstract A small molecule library containing 480 known bioactive compounds was screened for antiviral activity against poliovirus (PV) using a cellular fluorescence resonance energy transfer (FRET) assay for viral protease activity. The infected reporter cells treated with the viral replication-suppressing compounds were examined via fluorescence microscope 7.5h postinfection. Twelve molecules showed moderate to potent antiviral activity at concentrations less than 32μM during the primary screening. Three compounds, anisomycin, linoleic acid, and lycorine, were chosen for validation. A dose-dependent cytotoxicity assay and a secondary screening using conventional plaque assay were conducted to confirm the results. The developed method can be used for rapid screening for molecules with antiviral activity.


title: Role of viral bioaerosols in nosocomial infections and measures for prevention and control

text: Abstract The presence of patients with diverse pathologies in hospitals results in an environment that can be rich in various microorganisms including respiratory and enteric viruses, leading to outbreaks in hospitals or spillover infections to the community. All hospital patients are at risk of nosocomial viral infections, but vulnerable groups such as older adults, children and immuno-compromised/-suppressed patients are at particular risk of severe outcomes including prolonged hospitalization or death. These pathogens could transmit through direct or indirect physical contact, droplets or aerosols, with increasing evidence suggesting the importance of aerosol transmission in nosocomial infections of respiratory and enteric viruses. Factors affecting the propensity to transmit and the severity of disease transmitted via the aerosol route include the biological characteristics affecting infectivity of the viruses and susceptibility of the host, the physical properties of aerosol particles, and the environmental stresses that alter these properties such as temperature and humidity. Non-specific systematic and individual-based interventions designed to mitigate the aerosol route are available although empirical evidence of their effectiveness in controlling transmission of respiratory and enteric viruses in healthcare settings are sparse. The relative importance of aerosol transmission in healthcare setting is still an on-going debate, with particular challenge being the recovery of infectious viral bioaerosols from real-life settings and the difficulty in delineating transmission events that may also be a result of other modes of transmission. For the prevention and control of nosocomial infections via the aerosol route, more research is needed on identifying settings, medical procedures or equipment that may be associated with an increased risk of aerosol transmission, including defining which procedures are aerosol-generating; and on the effectiveness of systematic interventions on aerosol transmission of respiratory and enteric viruses in healthcare settings.


title: Ensuring HIV Data Availability, Transparency and Integrity in the MENA Region: Comment on "Improving the Quality and Quantity of HIV Data in the Middle East and North Africa: Key Challenges and Ways Forward"

text: In this commentary, we elaborate on the main points that Karamouzian and colleagues have made about HIV data scarcity in Middle Eastern and North African (MENA) countries. Without accessible and reliable data, no epidemic can be managed effectively or efficiently. Clearly, increased investments are needed to bolster capabilities to capture and interpret HIV surveillance data. We believe that this enhanced capacity can be achieved, in part, by leveraging and repurposing existing data platforms, technologies and patient cohorts. An immediate modest investment that capitalizes on available infrastructure can generate data on the HIV burden and spread that can be persuasive for MENA policy-makers to intensify efforts to track and contain the growing HIV epidemic in this region. A focus on key populations will yield the most valuable data, including among men who have sex with men (MSM), transgender women and men, persons who inject drugs (PWIDs), female partners of high risk men and female sex workers.


title: Epidemiological characteristics and clinical features of 32 critical and 67 noncritical cases of COVID-19 in Chengdu

text: Abstract Background In December 2019, Wuhan, China, experienced an outbreak of coronavirus (COVID-19). The number of cases has increased rapidly, but information on the clinical characteristics remains limited. Objectives This paper describes the epidemiological and clinical characteristics of COVID-19. Early detection and identification of critically ill patients is necessary to facilitate scientific classification and treatment. Study design This study included a retrospective, single-center case series of 99 consecutively hospitalized patients with confirmed COVID-19 at Chengdu Public Health Clinical Medical Center in Chengdu, China, from January 16 to February 20, 2020. The final date of follow-up was February 23, 2020. We collected and analyzed epidemiological, demographic, clinical, laboratory, radiological, and treatment data. We compared outcomes of critically ill patients and noncritically ill patients. Results Of the 99 hospitalized patients with COVID-19, the median age was 49 years (minimum, 3 months; maximum, 87 years) and 51 (52 %) were men; 42 (42 %) had traveled to or lived in Wuhan and 48 (49 %) had come into close contact with patients with new coronavirus pneumonia; 41 (41 %) patients had underlying disease. Common symptoms included fever (85 [86 %]), dry cough (84 [85 %]), and fatigue (72 [73 %]). We analyzed the clinical characteristics of patients. We expressed the measurement data as mean ± standard deviation. We collected data for age (49.39 ± 18.45 years), number of hospital days (12.32 ± 6.70 days), and laboratory indicators. We compared critically ill and noncritically ill patients: p-values for age, C-reactive protein, high-sensitivity troponin T, prothrombin time, fibrin degradation products, D-Dimer, and CD4+ count were p < 0.001; and p-values for hospital days, white blood cell, neutrophil, lymphocyte, creatine kinase isoenzyme, myoglobin, N-terminal brain natriuretic peptide, and CD8+ count were p < 0.05. Conclusions We collected data from a single-center case series of 32 hospitalized patients who were critically ill with confirmed COVID-19 in Chengdu, China, and compared data with 67 noncritically ill patients. Elderly patients had chronic underlying diseases, notably cardiovascular disease. Higher C-reactive protein levels, higher levels of myocardial damage, and higher brain natriuretic peptide levels; lower white blood cells, neutrophils, and lymphocytes; and lower CD4 and CD8 counts could be used for early detection and identification of critically ill patients, and dynamic Data observation was more important than at a single moment.


title: Prevalence and Genetic Diversity Analysis of Human Coronavirus OC43 among Adult Patients with Acute Respiratory Infections in Beijing, 2012

text: To determine the prevalence, epidemiology and genetic diversity of human coronavirus OC43 (HCoV-OC43) among adult patients with acute respiratory infections (ARI) in Beijing,five hundred and fifty-nine nasopharyngeal swab samples were collected from adult patients with ARI in Beijing. The prevalence of HCoV-OC43 infection among these patients was assessed using two different OneStep reverse transcription polymerase chain reaction (RT-PCR) assays. The epidemiological profiles of the patients with HCoV-OC43 infection were described. Partial S and N genes of HCoV-OC43 circulating strains were sequenced followed by phylogenetic analysis and amino acid alignment. Our results showed that the prevalence of HCoV-OC43 infection was 12.52% (95% CI: 9.78–15.26%), and the epidemic peak occurred in autumn. Fifty partial S and 40 partial N fragments were obtained from these patients. Phylogenetic analysis based on neighbour-joining method showed that at least three distinct clusters (A, B, C/D) of HCoV-OC43 strains were circulating among adult patients with ARI in Beijing. In addition, some novel unique clusters (UNT) of HCoV-OC43 were found in the S- and N-based phylogenetic trees. Furthermore, consensus amino acids substitutes for each cluster were also found after alignment of partial S or N sequence coding region in this study. In conclusion, we herein describe the prevalence of HCoV-OC43 among adult patients and provide substantial evidence for the genetic diversity of HCoV-OC43 circulating in Beijing.


title: Correlation between arterial blood gas test and CT volumetry in patients with SARS-CoV-2 in the emergency department

text: • The severity of SARS-CoV-2 patients is difficult to quickly assess in the ED. • The ABG test is a quick and easy tool that can help identify more severe patients. • CT cannot be used on all suspected SARS-CoV-2 infected patients admitted in ED. • The CT volumetry correlate well with the values of severity reported by the ABG test.


title: RECOMENDACIONES DE LA ASOCIACIÓN ESPAÑOLA DE NEUROGASTROENTEROLOGIA Y MOTILIDAD (ASENEM) PARA EL REINICIO DE LA ACTIVIDAD DE LOS LABORATORIOS DE MOTILIDAD DIGESTIVA, TRAS EL CONFINAMIENTO POR EL ESTADO DE ALARMA DECRETADO A RAIZ DE LA PANDEMIA POR COVID-19

text: Resumen El coronavirus del síndrome respiratorio agudo severo tipo 2 (conocido por sus siglas en inglés, SARS-CoV-2) ha sido responsable del brote de la denominada enfermedad por coronavirus de 2019 (COVID-19), que ha llegado a tener la consideración de pandemia. Las estrategias adoptadas para su prevención han incluido medidas de distanciamiento social, así como la modificación, reducción o interrupción de gran parte de la actividad sanitaria habitual. Esto ha afectado de forma muy notable a la asistencia prestada en las Unidades de Motilidad Digestiva. Superado el pico de mortalidad y contagios por la infección, se ha observado durante las últimas semanas en España y otros países europeos, una reducción paulatina en las cifras de transmisión. Sin embargo, el riesgo de reactivación sigue siendo alto, por lo que es necesario disponer de una planificación que permita a los centros sanitarios reiniciar con seguridad para pacientes y profesionales, las exploraciones instrumentales vinculadas al manejo de la patología motora. La Asociación Española de Neurogastroenterología y Motilidad (ASENEM) ha elaborado una serie de recomendaciones prácticas basadas en la evidencia científica disponible y en el consenso de un panel de expertos, y adaptadas a los riesgos inherentes a cada actividad. Se incluyen propuestas de protección individual, pero también medidas organizativas y estructurales, cuyo objetivo es permitir reanudar progresivamente las exploraciones, minimizando la posibilidad de contagio. Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was responsible for the outbreak of the 2019 coronavirus disease (COVID-19), which is now considered as a pandemic. The prevention strategies adopted have included social distancing measures and the modification, reduction or interruption of a large proportion of routine healthcare activity. This has had a significant impact on the care provided in Gastrointestinal Motility Units. Having passed the peak, in terms of mortality and infections, a gradual reduction in transmission figures has been observed in Spain and other European countries. The risk of reactivation, however, remains high, so it is necessary to have a plan in place that allows healthcare centres to safely resume, for their patients and professionals, instrumental examinations linked to the management of motor pathology. Based on the available scientific evidence and the consensus of a panel of experts, the Spanish Association of Neurogastroenterology and Motility (ASENEM) has drawn up a series of practical recommendations, which have been adapted to the risks inherent in each activity. These include individual protection proposals, as well as organisational and structural measures, which are conceived to allow for the gradual resumption of examinations while minimising the possibility of contagion.


title: Plasmapheresis treatment in COVID-19–related autoimmune meningoencephalitis: Case series

text: Abstract Severe SARS-CoV-2 (COVID-19) infection has the potential for a high mortality rate. In this paper, we report the results of plasmapheresis treatment in a series of severely ill patients with COVID-19–related autoimmune meningoencephalitis in the Intensive Care Unit ICU.


title: Identification of picobirnavirus from faeces of Italian children suffering from acute diarrhea

text: Polyacrylamide gel electrophoresis of nucleic acid extracted from stool samples of diarrhoeic children revealed in 3 out of 690 (0.43 %) specimens two electrophoretic bands with a migration pattern characteristic of picobirnavirus ds-RNA. In none of the 92 control children were similar bands detected. No other potential enteric pathogens were found in the patients with picobirnavirus infection.


title: Detecting specific cytotoxic T lymphocytes against SARS-coronavirus with DimerX HLA-A2:Ig fusion protein

text: Abstract To assess specific cytotoxic T lymphocytes (CTLs) against Severe acute respiratory syndrome (SARS)-coronavirus, a modified DimerX flow cytometry assay was performed with peripheral blood mononuclear cell (PBMC) from HLA-A2+ SARS-recovered donors at different time points post disease. CD8+DimerX-S1203+ CTLs were detected in the PBMC from these donors up to 3 months after recovery. The percentages of CD8+DimerX-S1203+ cells paralleled the numbers of interferon-γ-positive spots in an ELISPOT assay using the same antigenic peptide. In conclusion, DimerX-based flow cytometry staining may prove to be a real-time method to screen for CTL directed at epitopes from a newly identified virus.


title: Zelf covid-19 gehad: ‘Ik heb me nog nooit zo ellendig gevoeld’

text: Volgens het RIVM maakten meer dan 14.000 Nederlandse zorgverleners covid-19 door.(1) Dat dit ingrijpend is en het herstel geen kwestie van dagen, blijkt uit de ervaringen van verpleegkundigen Lotte, Veerle en Jenieke.


title: COVID‐19 drug repurposing: Summary statistics on current clinical trials and promising untested candidates

text: Repurposing of existing antiviral drugs, immunological modulators, and supportive therapies represents a promising path toward rapidly developing new control strategies to mitigate the devastating public health consequences of the COVID‐19 pandemic. A comprehensive text‐mining and manual curation approach was used to comb and summarize the most pertinent information from existing clinical trials and previous efforts to develop therapies against related betacoronaviruses, particularly SARS and MERS. In contrast to drugs in current trials, which have been derived overwhelmingly from studies on taxonomically unrelated RNA viruses, a number of untested small molecule antivirals had previously demonstrated remarkable in vitro specificity for SARS‐CoV or MERS‐CoV, with high selectivity indices, EC(50), and/or IC(50). Due to the rapid containment of the prior epidemics, however, these were generally not followed up with in vivo animal studies or clinical investigations, and thus largely overlooked as treatment prospects in the current COVID‐19 trials. This brief review summarizes and tabulates core information on recent or ongoing drug repurposing‐focused clinical trials, while detailing the most promising untested candidates with prior documented success against the etiologic agents of SARS and/or MERS.


title: Collaborative Antimicrobial Stewardship Working with Microbiology

text: There have been tremendous advances in methodologies available for detection and identification of organisms causing infections. Providers can now obtain identification results and antimicrobial susceptibility results in a shorter period of time. However, declining health care resources highlight the importance of selecting the right test at the right time to maximize diagnostic benefits. Therefore, the role of the antimicrobial stewardship team in the clinical microbiology laboratory has expanded to include diagnostic stewardship and provision of guidance on test selection for diagnosis and management of infection. This review focuses on the experience of our group in collaborative stewardship, emphasizing successes and challenges.


title: Purification and characterization of monoclonal IgG antibodies recognizing Ebola virus glycoprotein

text: PURPOSE: The goal of this study was to purify and characterize Ebola virus glycoprotein (GP)-specific IgG antibodies from hybridoma clones. MATERIALS AND METHODS: For hybridoma production, mice were injected by intramuscular-electroporation with GP DNA vaccines, and boosted with GP vaccines. The spleen cells were used for producing GP-specific hybridoma. Enzyme-linked immunosorbent assay, Western blot assay, flow cytometry, and virus-neutralizing assay were used to test the ability of monoclonal IgG antibodies to recognize GP and neutralize Ebola virus. RESULTS: Twelve hybridomas, the cell supernatants of which displayed GP-binding activity by enzyme-linked immunosorbent assay and the presence of both IgG heavy and light chains by Western blot assay, were chosen as a possible IgG producer. Among these, five clones (C36-1, D11-3, D12-1, D34-2, and E140-2) were identified to secrete monoclonal IgG antibodies. When the monoclonal IgG antibodies from the 5 clones were tested for their antigen specificity, they recognized GP in an antigen-specific and IgG dose-dependent manner. They remained reactive to GP at the lowest tested concentrations (1.953–7.8 ng/mL). In particular, IgG antibodies from clones D11-3, D12-1, and E140-2 recognized the native forms of GP expressed on the cell surface. These antibodies were identified as IgG1, IgG2a, or IgG2b kappa types and appeared to recognize the native forms of GP, but not the denatured forms of GP, as determined by Western blot assay. Despite their GP-binding activity, none of the IgG antibodies neutralized Ebola virus infection in vitro, suggesting that these antibodies are unable to neutralize Ebola virus infection. CONCLUSION: This study shows that the purified IgG antibodies from 5 clones (C36-1, D11-3, D12-1, D34-2, and E140-2) possess GP-binding activity but not Ebola virus-neutralizing activity.


title: CHAPTER 14 RABBITS

text: Publisher Summary This chapter provides an overview of the biology and medical care of rabbits. There are about 50 different breeds of domestic rabbits. Rabbits have very thin and delicate skin that is covered with fine fur comprised of both a soft undercoat and stiff guard hairs. Care must be taken when clipping fur because the skin is prone to tearing. A rabbit enclosure should be large enough to provide a sleeping space, eating space, and latrine. Animals housed for long periods of time should also have ample room to exercise. The enclosure should be tall enough to allow the rabbit to sit up and not have its ears touch the top of the cage. Because rabbits are prone to heatstroke, they should be housed in temperatures ranging from 60°F to 75°F. If rabbits are housed outdoors, they must have access to shade and clean water, and the shelter should protect them from the elements as well as from predators. The ideal substrate for rabbits is grass hay; however, for indoor, caged rabbits, a foam rubber pad or a towel covered with newspaper and a thick layer of timothy hay can also be used.


title: Viral contamination of aerosol and surfaces through toilet use in health care and other settings

text: BACKGROUND: The airborne spreading of enteric viruses can occur through the aerosol and droplets produced by toilet flushing. These can contaminate the surrounding environment, but few data exist to estimate the risk of exposure and infection. For this reason environmental monitoring of air and selected surfaces was carried out in 2 toilets of an office building and in 3 toilets of a hospital before and after cleaning operations. METHODS: To reveal the presence of norovirus, enterovirus, rhinovirus, human rotavirus, and Torque teno virus and to quantify human adenovirus and bacteria counts, molecular and cultural methods were used. RESULTS: On the whole, viruses were detected on 78% of surfaces and in 81% of aerosol. Among the researched viruses, only human adenovirus and Torque teno virus were found in both surface and air samples. In several cases the same adenovirus strain was concurrently found in all matrices. Bacterial counts were unrelated to viral presence and cleaning did not seem to substantially reduce contamination. CONCLUSIONS: The data collected in our study confirm that toilets are an important source of viral contamination, mainly in health care settings, where disinfection can have a crucial role in preventing virus spread.


The Hidden Victims of COVID-19 Pandemic: Congenital Heart Disease Patients


title: Investigation of three clusters of COVID-19 in Singapore: implications for surveillance and response measures

text: BACKGROUND: Three clusters of coronavirus disease 2019 (COVID-19) linked to a tour group from China, a company conference, and a church were identified in Singapore in February, 2020. METHODS: We gathered epidemiological and clinical data from individuals with confirmed COVID-19, via interviews and inpatient medical records, and we did field investigations to assess interactions and possible modes of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Open source reports were obtained for overseas cases. We reported the median (IQR) incubation period of SARS-CoV-2. FINDINGS: As of Feb 15, 2020, 36 cases of COVID-19 were linked epidemiologically to the first three clusters of circumscribed local transmission in Singapore. 425 close contacts were quarantined. Direct or prolonged close contact was reported among affected individuals, although indirect transmission (eg, via fomites and shared food) could not be excluded. The median incubation period of SARS-CoV-2 was 4 days (IQR 3–6). The serial interval between transmission pairs ranged between 3 days and 8 days. INTERPRETATION: SARS-CoV-2 is transmissible in community settings, and local clusters of COVID-19 are expected in countries with high travel volume from China before the lockdown of Wuhan and institution of travel restrictions. Enhanced surveillance and contact tracing is essential to minimise the risk of widespread transmission in the community. FUNDING: None.


title: Diarrhea caused by primarily non-gastrointestinal infections

text: Infectious diseases that do not primarily affect the gastrointestinal tract can cause severe diarrhea. The pathogenesis of this kind of diarrhea includes cytokine action, intestinal inflammation, sequestration of red blood cells, apoptosis and increased permeability of endothelial cells in the gut microvasculature, and direct invasion of gut epithelial cells by various infectious agents. Of the travel-associated systemic infections presenting with fever, diarrhea occurs in patients with malaria, dengue fever and SARS. Diarrhea also occurs in patients with community-acquired pneumonia, when it is suggestive of legionellosis. Diarrhea can also occur in patients with systemic bacterial infections. In addition, although diarrhea is rare in patients with early Lyme borreliosis, the incidence is higher in those with other tick-borne infections, such as ehrlichiosis, tick-borne relapsing fever and Rocky Mountain spotted fever. Unfortunately, it is often not established whether diarrhea is an initial symptom or develops during the course of the disease. The real incidence of diarrhea in some infectious diseases must also be questioned because it could represent an adverse reaction to antibiotics.


title: Chapter 2 Prediction of Medicinal Properties Using Mathematical Models and Computation, and Selection of Plant Materials

text: Abstract In any phytochemical drug discovery programme, one of the major issues is the appropriate selection of target plant species that may provide lead for new drug discovery and development. Conducting research without any working hypotheses may produce serendipitous discoveries, but the chances of success are much slimmer than any information-based targeted approach. Therefore, the plant selection process is extremely important for ensuring success. In recent years, there have been significant amounts of work involving applications of various mathematical modelling and computational techniques to predict medicinal properties of plants, and thus to provide information-based selection of plant materials for further studies aiming at potential drug discovery and development. This chapter presents an overview of methods and processes involved in plant selection by utilizing various mathematical modelling and computational techniques.


title: Syndromic Surveillance for Local Outbreaks of Lower-Respiratory Infections: Would It Work?

text: BACKGROUND: Although syndromic surveillance is increasingly used to detect unusual illness, there is a debate whether it is useful for detecting local outbreaks. We evaluated whether syndromic surveillance detects local outbreaks of lower-respiratory infections (LRIs) without swamping true signals by false alarms. METHODS AND FINDINGS: Using retrospective hospitalization data, we simulated prospective surveillance for LRI-elevations. Between 1999–2006, a total of 290762 LRIs were included by date of hospitalization and patients place of residence (>80% coverage, 16 million population). Two large outbreaks of Legionnaires disease in the Netherlands were used as positive controls to test whether these outbreaks could have been detected as local LRI elevations. We used a space-time permutation scan statistic to detect LRI clusters. We evaluated how many LRI-clusters were detected in 1999–2006 and assessed likely causes for the cluster-signals by looking for significantly higher proportions of specific hospital discharge diagnoses (e.g. Legionnaires disease) and overlap with regional influenza elevations. We also evaluated whether the number of space-time signals can be reduced by restricting the scan statistic in space or time. In 1999–2006 the scan-statistic detected 35 local LRI clusters, representing on average 5 clusters per year. The known Legionnaires' disease outbreaks in 1999 and 2006 were detected as LRI-clusters, since cluster-signals were generated with an increased proportion of Legionnaires disease patients (p:<0.0001). 21 other clusters coincided with local influenza and/or respiratory syncytial virus activity, and 1 cluster appeared to be a data artifact. For 11 clusters no likely cause was defined, some possibly representing as yet undetected LRI-outbreaks. With restrictions on time and spatial windows the scan statistic still detected the Legionnaires' disease outbreaks, without loss of timeliness and with less signals generated in time (up to 42% decline). CONCLUSIONS: To our knowledge this is the first study that systematically evaluates the performance of space-time syndromic surveillance with nationwide high coverage data over a longer period. The results show that syndromic surveillance can detect local LRI-outbreaks in a timely manner, independent of laboratory-based outbreak detection. Furthermore, since comparatively few new clusters per year were observed that would prompt investigation, syndromic hospital-surveillance could be a valuable tool for detection of local LRI-outbreaks.


title: Multisystem Inflammatory Syndrome in U.S. Children and Adolescents

text: BACKGROUND: Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19) is important, given the clinical and public health implications of the syndrome. METHODS: We conducted targeted surveillance for MIS-C from March 15 to May 20, 2020, in pediatric health centers across the United States. The case definition included six criteria: serious illness leading to hospitalization, an age of less than 21 years, fever that lasted for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse-transcriptase polymerase chain reaction (RT-PCR), antibody testing, or exposure to persons with Covid-19 in the past month. Clinicians abstracted the data onto standardized forms. RESULTS: We report on 186 patients with MIS-C in 26 states. The median age was 8.3 years, 115 patients (62%) were male, 135 (73%) had previously been healthy, 131 (70%) were positive for SARS-CoV-2 by RT-PCR or antibody testing, and 164 (88%) were hospitalized after April 16, 2020. Organ-system involvement included the gastrointestinal system in 171 patients (92%), cardiovascular in 149 (80%), hematologic in 142 (76%), mucocutaneous in 137 (74%), and respiratory in 131 (70%). The median duration of hospitalization was 7 days (interquartile range, 4 to 10); 148 patients (80%) received intensive care, 37 (20%) received mechanical ventilation, 90 (48%) received vasoactive support, and 4 (2%) died. Coronary-artery aneurysms (z scores ≥2.5) were documented in 15 patients (8%), and Kawasaki’s disease–like features were documented in 74 (40%). Most patients (171 [92%]) had elevations in at least four biomarkers indicating inflammation. The use of immunomodulating therapies was common: intravenous immune globulin was used in 144 (77%), glucocorticoids in 91 (49%), and interleukin-6 or 1RA inhibitors in 38 (20%). CONCLUSIONS: Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents. (Funded by the Centers for Disease Control and Prevention.)


title: Harm reduction policy in Taiwan: toward a comprehensive understanding of its making and effects

text: BACKGROUND: In response to the spread of HIV caused by needle sharing among injection drug users (IDUs), the Taiwan Centers for Disease Control implemented a pilot harm reduction program in 2005 that expanded nationwide in 2006. The policy led to a significant reduction in the number of HIV-positive cases among IDUs in 4 years. METHODS: This article aims to provide a critical evaluation of this harm reduction policy in Taiwan. The research leading to this article included a thorough literature review and in-depth interviews with 31 active policy participants, including people working in hospitals, the academia, non-governmental organizations, community pharmacies, the legal system, and health authorities at both the central and local levels. The collected data were analyzed on the basis of situational analysis. RESULTS: The article examines the policy success by showing how this policy was assembled and by exposing the frictions and adjustments during its formation and implementation. Inter-departmental conflicts within or without the government and the efforts to coordinate them are addressed, and the transnational dimensions of this harm reduction policy are also discussed. The article then reflects on the effects of the policy and asks where the line should be drawn between what is harm reduction and what is not. CONCLUSIONS: This case illustration reveals the complexity of understanding an assembled health policy that involves multiple participants. The article intends to render an analytic account to enable a comparison with similar policies in other countries.


Retinal pathology in multiple sclerosis: insight into the mechanisms of neuronal pathology


title: Inward international students in China and their contributions to global common goods

text: This study identifies the (global) common goods produced and augmented by inward student mobility and its relevance to national policies and strategies in China by interviewing 27 policy-makers, university leaders, and academics, as well as international students. Most importantly, it develops a new framework for interpreting inward student mobility through the lens of (global) common goods, with benefit, influence, and balance as the three key elements. The findings of this study indicate that inward international students contribute to global common goods in the aspects of cultural diversity, global talents, improved policies, and practices, etc. (benefit). Key policies related to inward international students are generally supportive, and meanwhile compatible with these global common goods to a large extent (influence). Though some problems and tensions are observed in this study, constructive solutions have already been proposed by both the Chinese government and HEIs (balance).


title: Global task force for influenza

text: Early detection and rapid response to bird flu, on a global scale, will drastically cut the costs of dealing with a full-blown human flu pandemic, argue Ron Fouchier, Thijs Kuiken, Guus Rimmelzwaan and Albert Osterhaus.


title: CD13 in cell adhesion: aminopeptidase N (CD13) mediates homotypic aggregation of monocytic cells

text: Homotypic aggregation (HA) of cells plays key roles in physiological and pathological processes, such as embryogenesis, immune responses, angiogenesis, tumor cell invasion, and metastasis. Aminopeptidase N (CD13) has been implicated in most of these phenomena, although its participation has been attributed to its enzymatic activity, while its role as an adhesion molecule has been almost unexplored. Here, we show that certain anti‐CD13 monoclonal antibodies induce HA of monocytic U‐937 cells, independently of their effect on enzymatic activity. The phenomenon is related to binding to a specific site on the CD13 molecule and is independent of integrins. It is abrogated by low temperature, by the glycolysis inhibitor 2‐deoxyglucose, and by inhibitors of tyrosine and mitogen‐activated protein kinases. The inhibitor of microtubule polymerization colchicine has a synergistic effect on CD13‐mediated aggregation, suggesting an inhibitory role of microtubules in this process. Finally, during HA, CD13 actively redistributes to the zones of cell‐cell contact, as determined by live cell imaging studies, demonstrating a direct role of CD13 in the adhesion phenomenon. Together, these data show for the first time the participation of CD13 in monocytic cell adhesion.


title: European and United Kingdom COVID-19 Pandemic Experience: The same but different

text: The global healthcare landscape has changed dramatically and rapidly in 2020. This has had an impact upon paediatricians and in particular respiratory paediatricians. The effects in Europe, with its mature healthcare system, have been far faster and greater than most authorities anticipated. Within six weeks of COVID-19 being declared a public health emergency by the World Health Organisation [WHO] in China, Europe had become the new epicentre of disease. A pandemic was finally declared by the WHO on March 11th 2020. Continued international travel combined with the slow response of some political leaders and a variable focus on economic rather than health consequences resulted in varying containment strategies in response to the threat of the initial wave of the pandemic. It is likely that this variation has contributed to widely differing outcomes across Europe. Common to all countries was the stark lack of preparations and initially poor co-ordination of responses between levels of government to this unforeseen but not unheralded global health crisis. In this article we highlight the impact of the first wave of the COVID-19 pandemic in Italy, Austria, Germany, and the United Kingdom.


title: PATRIC: The VBI PathoSystems Resource Integration Center

text: The PathoSystems Resource Integration Center (PATRIC) is one of eight Bioinformatics Resource Centers (BRCs) funded by the National Institute of Allergy and Infection Diseases (NIAID) to create a data and analysis resource for selected NIAID priority pathogens, specifically proteobacteria of the genera Brucella, Rickettsia and Coxiella, and corona-, calici- and lyssaviruses and viruses associated with hepatitis A and E. The goal of the project is to provide a comprehensive bioinformatics resource for these pathogens, including consistently annotated genome, proteome and metabolic pathway data to facilitate research into counter-measures, including drugs, vaccines and diagnostics. The project's curation strategy has three prongs: ‘breadth first’ beginning with whole-genome and proteome curation using standardized protocols, a ‘targeted’ approach addressing the specific needs of researchers and an integrative strategy to leverage high-throughput experimental data (e.g. microarrays, proteomics) and literature. The PATRIC infrastructure consists of a relational database, analytical pipelines and a website which supports browsing, querying, data visualization and the ability to download raw and curated data in standard formats. At present, the site warehouses complete sequences for 17 bacterial and 332 viral genomes. The PATRIC website () will continually grow with the addition of data, analysis and functionality over the course of the project.


title: The 2019 coronavirus: Learning curves, lessons, and the weakest link

text: In the space of just six weeks, a new coronavirus, from a family that historically was not viewed as a global health concern, has become daily headline news around the globe. The 21st century marked its arrival with the emergence of three previously unknown coronaviruses. SARS-CoV (severe acute respiratory syndrome coronavirus) was recognized in November 2002 [1, 2], MERS-CoV (Middle East respiratory syndrome coronavirus) in June 2012 [3, 4], and 2019-nCoV in December 2019 [5]. Previously, human coronaviruses, known since the 1960s, were viewed as being only marginally relevant to the clinic, except for infants, the elderly, and immunocompromised individuals [1, 6, 7].


title: Improving an Escherichia coli-based biocatalyst for terpenol glycosylation by variation of the expression system

text: Glycosides are becoming increasingly more relevant for various industries as low-cost whole-cell-biocatalysts are now available for the manufacture of glycosides. However, there is still a need to optimize the biocatalysts. The aim of this work was to increase the titre of terpenyl glucosides in biotransformation assays with E. coli expressing VvGT14ao, a glycosyltransferase gene from grape (Vitis vinifera). Seven expression plasmids differing in the resistance gene, origin of replication, promoter sequence, and fusion protein tag were generated and transformed into four different E. coli expression strains, resulting in 18 strains that were tested for glycosylation efficiency with terpenols and a phenol. E. coli BL21(DE3)/pET-SUMO_VvGT14ao yielded the highest titres. The product concentration was improved 8.6-fold compared with E. coli BL21(DE3)pLysS/pET29a_VvGT14ao. The selection of a small solubility-enhancing protein tag and exploitation of the T7 polymerase-induction system allowed the formation of increased levels of functional recombinant protein, thereby improving the performance of the whole-cell biocatalyst. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10295-019-02184-4) contains supplementary material, which is available to authorized users.


title: Sarcocystis sp. encephalomyelitis in a cat

text: Abstract: A 5‐month‐old male neutered domestic shorthair cat was evaluated for spinal pain, ataxia, and anisocoria. Neuroanatomic localization indicated diffuse or multifocal central nervous system disease. On cerebrospinal fluid analysis, neutrophilic pleocytosis and intracellular protozoal merozoites were observed. The merozoites were oval, 2–4 μm in width and 4–6 μm in length, and had linear arrays of nuclear material concentrated at one pole. Serum was positive for Sarcocystis sp. antibodies and negative for Toxoplasma gondii antibodies. The organism was determined to be either Sarcocystis neurona or Sarcocystis dasypi based on sequence analysis of the internal transcribed spacer 1 ribosomal RNA genomic region. Clinical disease resolved following treatment with 3 different protocols for protozoal infection. This case is the first to demonstrate the antemortem diagnosis and survival of a domestic cat with Sarcocystis sp.‐associated encephalomyelitis. Clinicians and cytopathologists should include Sarcocystis sp. as a differential for feline inflammatory central nervous system disease characterized by neutrophilic pleocytosis.


title: Nipah virus epidemic in southern India and emphasizing “One Health” approach to ensure global health security

text: Nipah virus (NiV) encephalitis first reported in “Sungai Nipah” in Malaysia in 1999 has emerged as a global public health threat in the Southeast Asia region. From 1998 to 2018, more than 630 cases of NiV human infections were reported. NiV is transmitted by zoonotic (from bats to humans, or from bats to pigs, and then to humans) as well as human-to-human routes. Deforestation and urbanization of some areas have contributed to greater overlap between human and bat habitats resulting in NiV outbreaks. Common symptoms of NiV infection in humans are similar to that of influenza such as fever and muscle pain and in some cases, the inflammation of the brain occurs leading to encephalitis. The recent epidemic in May 2018 in Kerala for the first time has killed over 17 people in 7 days with high case fatality and highlighted the importance of One Health approach. The diagnosis is often not suspected at the time of presentation and creates challenges in outbreak detection, timely control measures, and outbreak response activities. Currently, there are no drugs or vaccines specific for NiV infection although this is a priority disease on the World Health Organization's agenda. Antivirals (Ribavirin, HR2-based fusion inhibitor), biologicals (convalescent plasma, monoclonal antibodies), immunomodulators, and intensive supportive care are the mainstay to treat severe respiratory and neurologic complications. There is a great need for strengthening animal health surveillance system, using a One Health approach, to detect new cases and provide early warning for veterinary and human public health authorities.


title: Design and application of 60mer oligonucleotide microarray in SARS coronavirus detection

text: The 60mer oligonucleotide microarray was designed and applied to detecting of SARS (severe acute respiratory syndrome) coronavirus. Thirty 60mer specific oligos were designed to cover the whole genome of the first submitted coronavirus strain, according to the sequence of TOR2 (GENEBANK Accession: AY274119). These primers were synthesized and printed into a microarray with 12 ×12 spots. RNAs were extracted from the throat swab and gargling fluid of SARS patients and reverse-transcripted into the double strand cDNAs. The cDNAs were prepared as restricted cDNA fragments by the restriction display (RD) technique and labeled by PCR with the Cy5-universal primer. The labeled samples were then applied to the oligo microarray for hybridization. The diagnostic capability of the microarray was evaluated after the washing and scanning steps. The scanning result showed that samples of SARS patients were hybridized with multiple SARS probes on the microarray, and there is no signal on the negative and blank controls. These results indicate that the genome of SARS coronavirus can be detected in parallel by the 60mer oligonucleotide microarray, which can improve the positive ratio of the diagnosis. The oligo microarray can also be used for monitoring the behavior of the virus genes in different stages of the disease status.


title: Human Coronavirus 229E Remains Infectious on Common Touch Surface Materials

text: The evolution of new and reemerging historic virulent strains of respiratory viruses from animal reservoirs is a significant threat to human health. Inefficient human-to-human transmission of zoonotic strains may initially limit the spread of transmission, but an infection may be contracted by touching contaminated surfaces. Enveloped viruses are often susceptible to environmental stresses, but the human coronaviruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) have recently caused increasing concern of contact transmission during outbreaks. We report here that pathogenic human coronavirus 229E remained infectious in a human lung cell culture model following at least 5 days of persistence on a range of common nonbiocidal surface materials, including polytetrafluoroethylene (Teflon; PTFE), polyvinyl chloride (PVC), ceramic tiles, glass, silicone rubber, and stainless steel. We have shown previously that noroviruses are destroyed on copper alloy surfaces. In this new study, human coronavirus 229E was rapidly inactivated on a range of copper alloys (within a few minutes for simulated fingertip contamination) and Cu/Zn brasses were very effective at lower copper concentration. Exposure to copper destroyed the viral genomes and irreversibly affected virus morphology, including disintegration of envelope and dispersal of surface spikes. Cu(I) and Cu(II) moieties were responsible for the inactivation, which was enhanced by reactive oxygen species generation on alloy surfaces, resulting in even faster inactivation than was seen with nonenveloped viruses on copper. Consequently, copper alloy surfaces could be employed in communal areas and at any mass gatherings to help reduce transmission of respiratory viruses from contaminated surfaces and protect the public health.


Metagenomics and the case of the deadly hamster


title: COVID-19-Related Severe Hypercoagulability in Patients Admitted to Intensive Care Unit for Acute Respiratory Failure

text: In late December 2019 an outbreak of a novel coronavirus (SARS-CoV-2) causing severe pneumonia (COVID-19) was reported in Wuhan, Hubei Province, China. A common finding in most COVID-19 patients is high D-dimer levels which are associated with a worse prognosis. We aimed to evaluate coagulation abnormalities via traditional tests and whole blood thromboelastometry profiles in a group of 22 (mean age 67 ± 8 years, M:F 20:2) consecutive patients admitted to the Intensive Care Unit of Padova University Hospital for acute respiratory failure due to COVID-19. Cases showed significantly higher fibrinogen and D-dimer plasma levels versus healthy controls ( p < 0.0001 in both comparisons). Interestingly enough, markedly hypercoagulable thromboelastometry profiles were observed in COVID-19 patients, as reflected by shorter Clot Formation Time (CFT) in INTEM ( p = 0.0002) and EXTEM ( p = 0.01) and higher Maximum Clot Firmness (MCF) in INTEM, EXTEM and FIBTEM ( p < 0.001 in all comparisons). In conclusion, COVID-19 patients with acute respiratory failure present a severe hypercoagulability rather than consumptive coagulopathy. Fibrin formation and polymerization may predispose to thrombosis and correlate with a worse outcome.


title: Antiviral applications of RNAi for coronavirus

text: Until the appearance of severe acute respiratory syndrome (SARS), caused by the SARS coronavirus (SARS-CoV) in early 2003, coronavirus infection was not considered to be serious enough to be controlled by either vaccination or specific antiviral therapy. It is now believed that the availability of antiviral drugs effective against SARS-CoV will be crucial for the control of future SARS outbreaks. Recently, RNA interference has been successfully used as a more specific and efficient method for gene silencing. RNA interference induced by small interfering RNA can inhibit the expression of viral antigens and so provides a new approach to the therapy of pathogenic viruses. This review provides an overview of current information on coronavirus and the application of small interfering RNA in viral therapeutics, with particular reference to SARS-CoV.


title: Similarity maps and pairwise predictions for transmission dynamics of COVID-19 with neural networks

text: Abstract On March 11, 2020, the World Health Organization declared COVID-19 as a pandemic. Since then, many countries have experienced the rapid transmission of this respiratory disease among their populations and have exercised many strategies to mitigate the spread of this disease. The prediction of the transmission dynamics serves important roles in designing mitigation strategies. However, due to the unknown characteristics of this disease, as well as the geographical and political factors, building efficient models of the dynamics for many countries is difficult. The objective of this study is to develop a transmission dynamics predictor that takes advantage of the time differences among many countries with respect to transmission of this disease, in that some countries experienced earlier outbreaks than others. The primary novelty of the proposed method is that, unlike many existing transmission predictors that require parameters based on prior knowledge of the epidemiology of past viruses, the proposed method only requires the transmission similarities between countries in the publicly available data for this current disease. In this paper, the viability and limitations of the proposed method are reported and discussed.


title: A Case-Control Study of Acute Respiratory Tract Infection in General Practice Patients in The Netherlands

text: Background. Acute respiratory tract infections (ARTIs) are responsible for considerable morbidity in the community, but little is known about the presence of respiratory pathogens in asymptomatic individuals. We hypothesized that asymptomatic persons could have a subclinical infection and thus act as a source of transmission. Methods. During the period of 2000–2003, all patients with ARTI who visited their sentinel general practitioner had their data reported to estimate the incidence of ARTI in Dutch general practices. A random selection of these patients (case patients) and an equal number of asymptomatic persons visiting for other complaints (control subjects) were included in a case-control study. Nose and throat swabs of participants were tested for a broad range of pathogens. Results. The overall incidence of ARTI was 545 cases per 10,000 person-years, suggesting that, in the Dutch population, an estimated 900,000 persons annually consult their general practitioner for respiratory complaints. Rhinovirus was most common in case patients (24%), followed by influenza virus type A (11%) and coronavirus (7%). Viruses were detected in 58% of the case patients, β-hemolytic streptococci group A were detected in 11%, and mixed infections were detected in 3%. Pathogens were detected in ∼30% of control subjects, particularly in the youngest age groups. Conclusion. This study confirms that most ARTIs are viral and supports the reserved policy of prescribing antibiotics. In both case and control subjects, rhinovirus was the most common pathogen. Of bacterial infections, only group A β-hemolytic streptococci were more common in case patients than in control subjects. Furthermore, we demonstrated that asymptomatic persons might be a neglected source of transmission.


title: Feeding behavior during sialodacryoadenitis viral infection in rats

text: Abstract Sialodacryoadenitis (SDA) is a highly contagious common viral infection in rats, akin to mumps in humans. Anorexia occurs during such viral infection. But the pattern of the decrease in food intake (a decrease in either meal size and meal number or both) during spontaneous viral infection has not been previously characterized. We observed the onset of anorexia and an abnormal feeding pattern during an opportunistic SDA viral infection in our rat colony. We thus studied seven male rats. Before the viral infection there was a positive association between food intake and meal number (P<.05). After infection food intake decreased by 68%. This occurred via a significant decrease in meal size (by 69%) (P<.05); and a nonsignificant decrease in meal number (P=.71). This pattern of decreased food intake is similar to that occurring during indomethacin-induced ulcerative ileitis, where we previously measured an increase in plasma tumor-necrosis factor (TNF)-α. Anorexia in response to bacterial lipopolysaccharide administration, which is also linked to plasma TNF-α, is however, caused only via a decrease in meal number. The differences in the decrease in the feeding pattern between the SDA viral and a bacterial infection suggest that factors other than TNF-α alone play a significant role in the mechanism of anorexia during a viral infection.


title: COVID 19 and laparoscopic surgeons, the Indian scenario - Perspective

text: Coronavirus Disease 2019(COVID 19) had emerged as a global pandemic in recent times. The healthcare sector is at the epicentre of this unprecedented global pandemic challenge. Hospitals all over the world have reduced the number of non-emergency surgeries in order to utilize the staff and resources in a more efficient way. Severe acute respiratory syndrome coronavirus (SARS-CoV-2) is most transmitted via respiratory droplets, but risk of transmission is hugely increased while doing aerosol generating procedures (AGPs). Laparoscopy remains the preferred surgical approach for most surgical indications. There is theoretical possibility of generation of aerosols contaminated with COVID-19 from leaked CO2 and smoke generation after energy device use. The aim of this paper is to review available evidence evaluating the risk of spread of COVID-19 during necessary laparoscopic procedures and to compile guidelines from relevant professional organizations to minimize this risk.


title: Modified N95 Mask Delivers High Inspired Oxygen Concentrations While Effectively Filtering Aerosolized Microparticles

text: STUDY OBJECTIVE: In a pandemic, hypoxic patients will require an effective oxygen (O(2)) delivery mask that protects them from inhaling aerosolized particles produced by others, as well as protecting the health care provider from exposure from the patient. We modified an existing N95 mask to optimize O(2) supplementation while maintaining respiratory isolation. METHODS: An N95 mask was modified to deliver O(2) by inserting a plastic manifold consisting of a 1-way inspiratory valve, an O(2) inlet and a gas reservoir. In a prospective repeated-measures study, we studied 10 healthy volunteers in each of 3 phases, investigating (1) the fractional inspiratory concentrations of O(2) (F(I)O(2)) delivered by the N95 O(2) mask, the Hi-Ox(80) O(2) mask, and the nonrebreathing mask during resting ventilation and hyperventilation, each at 3 O(2) flow rates; (2) the ability of the N95 mask, the N95 O(2) mask, and the nonrebreathing mask to filter microparticles from ambient air; and (3) to contain microparticles generated inside the mask. RESULTS: The F(I)O(2)s (median [range]) delivered by the Hi-Ox(80) O(2) mask, the N95 O(2) mask, and the nonrebreathing mask during resting ventilation, at 8 L/minute O(2) flow, were 0.90 (0.79 to 0.96), 0.68 (0.60 to 0.85), and 0.59 (0.52 to 0.68), respectively. During hyperventilation, the FiO(2)s of all 3 masks were clinically equivalent. The N95 O(2) mask, but not the nonrebreathing mask, provided the same efficiency of filtration of internal and external particles as the original N95, regardless of O(2) flow into the mask. CONCLUSION: An N95 mask can be modified to administer a clinically equivalent FiO(2) to a nonrebreathing mask while maintaining its filtration and isolation capabilities.


title: Comparative Antiviral Activity of Remdesivir and Anti-HIV Nucleoside Analogs against Human Coronavirus 229E (HCoV-229E)

text: Remdesivir is a nucleotide prodrug that is currently undergoing extensive clinical trials for the treatment of COVID-19. The prodrug is metabolized to its active triphosphate form and interferes with the action of RNA-dependent RNA polymerase of SARS-COV-2. Herein, we report the antiviral activity of remdesivir against human coronavirus 229E (HCoV-229E) compared to known anti-HIV agents. These agents included tenofovir (TFV), 4′-ethynyl-2-fluoro-2′-deoxyadenosine (EFdA), alovudine (FLT), lamivudine (3TC), and emtricitabine (FTC), known as nucleoside reverse-transcriptase inhibitors (NRTIs), and a number of 5′-O-fatty acylated anti-HIV nucleoside conjugates. The anti-HIV nucleosides interfere with HIV RNA-dependent DNA polymerase and/or act as chain terminators. Normal human fibroblast lung cells (MRC-5) were used to determine the cytotoxicity of the compounds. The study revealed that remdesivir exhibited an EC(50) value of 0.07 µM against HCoV-229E with TC(50) of > 2.00 µM against MRC-5 cells. Parent NRTIs were found to be inactive against (HCoV-229E) at tested concentrations. Among all the NRTIs and 5′-O-fatty acyl conjugates of NRTIs, 5′-O-tetradecanoyl ester conjugate of FTC showed modest activity with EC(50) and TC(50) values of 72.8 µM and 87.5 µM, respectively. These data can be used for the design of potential compounds against other coronaviruses.


title: Zika virus-induced neurological critical illness in Latin America: Severe Guillain-Barre Syndrome and encephalitis

text: Abstract Zika virus (ZIKAV) is classically described as causing minor symptoms in adult patients, however neurologic complications have been recognized. The recent outbreak in Central and South America has resulted in serious illness in some adult patients. We report adult patients in Latin America diagnosed with ZIKAV infection admitted to Intensive Care Units (ICUs). Methods Multicenter, prospective case series of adult patients with laboratory diagnosis of ZIKAV in 16 ICUs in 8 countries. Results Between December 1st 2015 and April 2nd 2016, 16 ICUs in 8 countries enrolled 49 critically ill patients with diagnosis of ZIKAV infection. We included 10 critically ill patients with ZIKAV infection, as diagnosed with RT-PCR, admitted to the ICU. Neurologic manifestations concordant with Guillain-Barre Syndrome (GBS) were present in all patients, although 2 evolved into an encephalitis-like picture. 2 cases died, one due to encephalitis, the other septic shock. Conclusions Differing from what was usually reported, ZIKAV infection can result in life-threatening neurologic illness in adults, including GBS and encephalitis. Collaborative reporting to identify severe illness from an emerging pathogen can provide valuable insights into disease epidemiology and clinical presentation, and inform public health authorities about acute care priorities.


title: Prophylactic host behaviour discourages pathogen exploitation

text: Much work has considered the evolution of pathogens, but little is known about how they respond to changes in host behaviour. We build a model of sublethal disease effects where hosts are able to choose to engage in prophylactic measures that reduce the likelihood of disease transmission. This choice is mediated by utility costs and benefits associated with prophylaxis, and the fraction of hosts engaged in prophylaxis is also affected by population dynamics. When prophylactic host behaviour occurs, we find that the level of pathogen host exploitation is reduced, by the action of selection, relative to the level that would otherwise be predicted in the absence of prophylaxis. Our work emphasizes the significance of the transmission-recovery trade-off faced by the pathogen and the ability of the pathogen to influence host prophylactic behaviour.


title: Evidence for an RNA pseudoknot loop-helix interaction essential for efficient −1 ribosomal frameshifting 1 1 Edited by D. E. Draper

text: Abstract RNA pseudoknots are structural elements that participate in a variety of biological processes. At −1 ribosomal frameshifting sites, several types of pseudoknot have been identified which differ in their organisation and functionality. The pseudoknot found in infectious bronchitis virus (IBV) is typical of those that possess a long stem 1 of 11-12 bp and a long loop 2 (30-164 nt). A second group of pseudoknots are distinguishable that contain stems of only 5 to 7 bp and shorter loops. The NMR structure of one such pseudoknot, that of mouse mammary tumor virus (MMTV), has revealed that it is kinked at the stem 1-stem 2 junction, and that this kinked conformation is essential for efficient frameshifting. We recently investigated the effect on frameshifting of modulating stem 1 length and stability in IBV-based pseudoknots, and found that a stem 1 with at least 11 bp was needed for efficient frameshifting. Here, we describe the sequence manipulations that are necessary to bypass the requirement for an 11 bp stem 1 and to convert a short non-functional IBV-derived pseudoknot into a highly efficient, kinked frameshifter pseudoknot. Simple insertion of an adenine residue at the stem 1-stem 2 junction (an essential feature of a kinked pseudoknot) was not sufficient to create a functional pseudoknot. An additional change was needed: efficient frameshifting was recovered only when the last nucleotide of loop 2 was changed from a G to an A. The requirement for an A at the end of loop 2 is consistent with a loop-helix contact similar to those described in other RNA tertiary structures. A mutational analysis of both partners of the proposed interaction, the loop 2 terminal adenine residue and two G·C pairs near the top of stem 1, revealed that the interaction was essential for efficient frameshifting. The specific requirement for a 3′-terminal A residue was lost when loop 2 was increased from 8 to 14 nt, suggesting that the loop-helix contact may be required only in those pseudoknots with a short loop 2.


title: The Axl receptor tyrosine kinase is a discriminator of macrophage function in the inflamed lung

text: Much of the biology surrounding macrophage functional specificity has arisen through examining inflammation-induced polarising signals, but this also occurs in homeostasis, requiring tissue-specific environmental triggers that influence macrophage phenotype and function. The TAM receptor family of receptor tyrosine kinases (Tyro3, Axl and MerTK) mediates the non-inflammatory removal of apoptotic cells by phagocytes through the bridging phosphatidylserine-binding molecules Gas6 or Protein S. We show that one such TAM receptor (Axl) is exclusively expressed on mouse airway macrophages, but not interstitial macrophages and other lung leukocytes, under homeostatic conditions and is constitutively ligated to Gas6. Axl expression is potently induced by GM-CSF expressed in the healthy and inflamed airway, and by type I interferon or TLR3 stimulation on human and mouse macrophages, indicating potential involvement of Axl in apoptotic cell removal under inflammatory conditions. Indeed, an absence of Axl does not cause sterile inflammation in health, but leads to exaggerated lung inflammatory disease upon influenza infection. These data imply that Axl allows specific identification of airway macrophages, and that its expression is critical for macrophage functional compartmentalisation in the airspaces or lung interstitium. We propose that this may be a critical feature to prevent excessive inflammation due to secondary necrosis of apoptotic cells that have not been cleared by efferocytosis.