title: Sinusitis in the common cold

text: Abstract Background: Acute community-acquired sinusitis is considered a bacterial complication of the common cold. Radiologic abnormalities in sinuses occur, however, in most patients with upper respiratory virus infections. Objective: Assessment of the occurrence, clinical profile, laboratory findings, and outcome of radiologically confirmed sinusitis was carried out as part of a common cold study in young adults. Methods: Clinical examinations and radiography of the paranasal sinuses were carried out on days 1, 7, and 21 in 197 patients with the common cold. The symptoms were recorded on diary cards on days 1 to 20. Ten viruses and 5 bacteria were studied as etiologic agents of common cold as reported earlier. Serum C reactive protein concentrations, erythrocyte sedimentation rates, and total white blood cell counts with differentials were determined in 40 randomized subjects on day 7. The effect of 6 days of intranasal fluticasone propionate treatment of the common cold in the prevention of sinusitis was analyzed. Results: On day 7, 39% of patients with the common cold in the placebo group (n = 98) had sinusitis, which we would prefer to call viral sinusitis. The symptoms of patients with sinusitis and those without it were not clinically distinguishable. Viral infection was detected in 81.6% of patients with sinusitis. No significantly increased levels of antibodies to bacteria were detected. Serum C reactive protein concentrations, erythrocyte sedimentation rates, and white blood cell counts were low in patients with sinusitis. All patients made a clinical recovery within 21 days without antibiotic treatment. Fluticasone propionate treatment tended to prevent paranasal sinusitis, especially in rhinovirus-positive subjects. Conclusion: Viral sinusitis frequently occurs in the early days of the common cold, but it is a self-limited illness. The sinuses should not be imaged in patients with the common cold if the signs and symptoms of illness gradually become less severe and no specific signs suggestive of bacterial sinusitis occur. (J Allergy Clin Immunol 1998;102:403-8.)


title: The 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 analyse the relative expression levels of the known torovirus proteins and transcripts, chimaeric 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 utilises a unique combination of discontinuous and non-discontinuous RNA synthesis to produce its subgenomic RNAs; 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 ORFs, located within the so-called 5’ UTR. 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. 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 subgenomic RNA molecules differs. Here we performed deep sequencing to determine how equine torovirus produces subgenomic RNAs. 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: Production of a Monoclonal Antibody Targeting the M Protein of MERS-CoV for Detection of MERS-CoV Using a Synthetic Peptide Epitope Formulated with a CpG–DNA–Liposome Complex

text: The Middle East respiratory syndrome-related coronavirus (MERS-CoV) contains four major structural proteins, the spike glycoprotein, nucleocapsid phosphoprotein, membrane (M) glycoprotein and small envelope glycoprotein. The M protein of MERS-CoV has a role in the morphogenesis or assembly of the virus and inhibits type I interferon expression in infected cells. Here, we produced a monoclonal antibody specific against the M protein of MERS-CoV by injecting BALB/c mice with a complex containing the epitope peptide and CpG–DNA encapsulated with a phosphatidyl-β-oleoyl-γ-palmitoyl ethanolamine (DOPE):cholesterol hemisuccinate (CHEMS). The monoclonal antibody was reactive to the epitope peptide of the M protein of MERS-CoV which was confirmed by western blotting and immunoprecipitations. Indirect immunofluorescence assay and confocal image analysis showed that the monoclonal antibody binds specifically to the M protein of MERS-CoV in the virus-infected cells. Further studies using this monoclonal antibody may provide important information on the function of the M protein and its future application in diagnostics.


title: Anti-inflammatory activity of cinnamon water extract in vivo and in vitro LPS-induced models

text: BACKGROUND: Cinnamon bark is one of the most popular herbal ingredients in traditional oriental medicine and possesses diverse pharmacological activities including anti-bacterial, anti-viral, and anti-cancer properties. The goal of this study is to investigate the in vivo and in vitro inhibitory effect of cinnamon water extract (CWE) on lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α and its underlying intracellular mechanisms. METHODS: CWE was orally administrated to mice for 6 days prior to intraperitoneal injection of LPS. Serum levels of TNF-α and interleukin (IL)-6 were determined 1 hour after LPS stimulation. Peritoneal macrophages from thioglycollate-injected mice were isolated and assayed for viability, cytokine expression and signaling molecules upon LPS stimulation. CWE was further fractioned according to molecular size, and the levels of total polyphenols and biological activities of each fraction were measured. RESULTS: The oral administration of CWE to mice significantly decreased the serum levels of TNF-α and IL-6. CWE treatment in vitro decreased the mRNA expression of TNF-α. CWE blocked the LPS-induced degradation of IκBα as well as the activation of JNK, p38 and ERK1/2. Furthermore, size-based fractionation of CWE showed that the observed inhibitory effect of CWE in vitro occurred in the fraction containing the highest level of total polyphenols. CONCLUSIONS: Treatment with CWE decreased LPS-induced TNF-α in serum. In vitro inhibition of TNF-α gene by CWE may occur via the modulation of IκBα degradation and JNK, p38, and ERK1/2 activation. Our results also indicate that the observed anti-inflammatory action of CWE may originate from the presence of polyphenols.


European Resuscitation Council Guidelines for Resuscitation 2010 Section 2. Adult basic life support and use of automated external defibrillators


title: Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients Recommendations of Centers for Disease Control, the Infectious Disease Society of America, and the American Society of Blood and Marrow Transplantation

text: Abstract CDC, the Infectious Diseases Society of America, and the American Society of Blood and Marrow Transplantation have cosponsored these guidelines for preventing opportunistic infections (OIs) among hematopoietic stem cell transplant (HSCT) recipients. The guidelines were drafted with the assistance of a working group of experts in infectious diseases, transplantation, and public health. For the purposes of this report, HSCT is defined as any transplantation of blood-or marrow-derived hematopoietic stem cells, regardless of transplant type (i.e., allogeneic or autologous) or cell source (i.e., bone marrow, peripheral blood, or placental or umbilical cord blood). Such OIs as bacterial, viral, fungal, protozoal, and helminth infections occur with increased frequency or severity among HSCT recipients. These evidence-based guidelines contain information regarding preventing OIs, hospital infection control, strategies for safe living after transplantation, vaccinations, and hematopoietic stem cell safety. The disease-specific sections address preventing exposure and disease for pediatric and adult and autologous and allogeneic HSCT recipients. The goal of these guidelines is twofold: to summarize current data and provide evidence-based recommendations regarding preventing OIs among HSCT patients. The guidelines were developed for use by HSCT recipients, their household and close contacts, transplant and infectious diseases physicians, HSCT center personnel, and public health professionals. For all recommendations, prevention strategies are rated by the strength of the recommendation and the quality of the evidence supporting the recommendation. Adhering to these guidelines should reduce the number and severity of OIs among HSCT recipients. Biol Blood Marrow Transplant 2000;6(6a):659-713; 715; 717-27; quiz 729-33.


title: Electrowetting-on-Dielectric System for COVID-19 Testing

text: The ongoing viral outbreak labeled COVID-19 is spreading rapidly across states and is posing a great threat to public health. Rapid identification of the virus in the population plays a crucial role in isolating the individual and breaking the transmission chain, apart from initiating an appropriate treatment procedure. Here, we discuss an electrowetting-on-dielectric (EWOD) technology that uses a microprocessor-controlled electrode array to merge a possibly infected sample carried by a liquid drop with a drop of a reagent to carry out the testing process. Changes in color occurring during the mixing process of the drops are imaged using a camera.


title: Immunohistological study of the immune system cells in paraffin-embedded tissues of conventional pigs

text: Abstract The distribution of different cells of the immune system has been studied in formalin-fixed paraffin-embedded tissues from conventionally reared healthy pigs, using immunohistological techniques. The samples collected were: lungs, tonsils, lymph nodes (mediastinal, mesenteric, inguinal and submandibular), pancreas, spleen, liver, kidney, adrenal gland, ileum and stomach. A total of six primary antibodies anti-CD3, anti-CD79α, Mac 387, anti-lysozyme, anti-CD45RA (3C3/9) and anti-SLA-II-DQ (BL2H5) were used with a standard avidin–biotin peroxidase (ABC) method. Anti-CD3 and anti-CD79α mAb-reacted, respectively with cells located in T cell areas and B cell areas. Mac 387 recognised circulating polymorphonuclear leukocytes, while anti-lysozyme-stained resident macrophages in all tissues. 3C3/9 and BL2H5, were assessed in formalin-fixed paraffin-embedded tissues for the first time. 3C3/9 identified B lymphocytes, in primary follicles and mantle zones, a subpopulation of T cells, especially located in the marginal zone of the spleen and a variable number of immunoblasts, in the germinal centres. BL2H5 reacted with B cells in the mantle zones of the follicles of lymphoid tissues, with dendritic and interdigitating cells in all studied lymphoid tissues and with a variable number of resting and activated T cells in the periarteriolar lymphoid sheath (PALs), marginal zone and red pulp of the spleen. Furthermore, it stained Kupffer and perivascular macrophages in the liver This study represents a detailed histological study of the distribution of the most important subpopulations of immune system cells in conventional, healthy pigs. In our view, these tools should be useful for future comparative studies in disease conditions.


title: Infection control practices for SARS in Lao People's Democratic Republic, Taiwan, and Thailand: Experience from mobile SARS containment teams, 2003

text: BACKGROUND: Despite available recommendations on infection control for severe acute respiratory syndrome (SARS), information is limited on actual practices in Asian hospitals during the epidemic. We describe practices observed by mobile SARS containment teams (mobile teams) during outbreak investigations. METHODS: We retrospectively summarized infection control practices observed in hospitals visited by mobile teams in the Lao People's Democratic Republic (PDR), Taiwan, and Thailand, during March and April 2003. RESULTS: Mobile teams investigated 22 reports of SARS in 20 hospitals (1, 5, and 14 hospitals in Lao PDR, Taiwan, and Thailand, respectively). Facilities ranged from urban hospitals with negative-pressure isolation rooms and high-efficiency particulate air filtration to rural hospitals with patient rooms open to outside air circulation and intermittent running water. At the time of mobile team visits, 5 (25%) hospitals implemented infection control practices consistent with World Health Organization recommendations on visitor policies, private negative-pressure rooms, and personal protective equipment. CONCLUSIONS: Early in the SARS epidemic, mobile teams found wide variations in infection control practices and resources among Asian hospitals evaluating patients for SARS, indicating the importance of ongoing assessment during SARS preparedness. Mobile teams are one mechanism to assess practices and promote implementation of recommended infection control measures.


title: The defective RNAs of Closteroviridae

text: The family Closteroviridae consists of two genera, Closterovirus and Ampelovirus with monopartite genomes transmitted respectively by aphids and mealybugs and the Crinivirus with bipartite genomes transmitted by whiteflies. The Closteroviridae consists of more than 30 virus species, which differ considerably in their phytopathological significance. Some, like beet yellows virus and citrus tristeza virus (CTV) were associated for many decades with their respective hosts, sugar beets and citrus. Others, like the grapevine leafroll-associated ampeloviruses 1, and 3 were also associated with their grapevine hosts for long periods; however, difficulties in virus isolation hampered their molecular characterization. The majority of the recently identified Closteroviridae were probably associated with their vegetative propagated host plants for long periods and only detected through the considerable advances in dsRNA isolation and sequencing of PCR amplified replicons. Molecular characterization of CTV and several other Closteroviridae revealed that, in addition to genomic and subgenomic RNAs, infected plants contain several different subviral defective RNAs (dRNAs). The roles and biological functions of dRNAs associated with Closteroviridae remain terra incognita.


title: Molecular characterisation and risk factor analysis of Cryptosporidium spp. in calves from Italy

text: To provide up-to-date information on the occurrence of Cryptosporidium in pre-weaned calves from Sardinia (Italy), the species implicated and their zoonotic potential, 147 faecal samples from 22 cattle herds were microscopically examined for Cryptosporidium oocysts; positive isolates were molecularly characterised. A questionnaire was developed to identify risk factors for Cryptosporidium infection. Overall, the percentage of positive calves and farms was 38.8 and 68.2%, respectively. The SSU rRNA-based PCR identified two Cryptosporidium species, Cryptosporidium parvum (95.8%) and C. bovis (4.2%). Sequence analyses of the glycoprotein (gp60) gene revealed that all C. parvum isolates belonged to the subtype family IIa (IIaA15G2R1 and IIaA16G3R1), with the exception of three isolates that belonged to the subtype family IId (IIdA20G1b and IIdA20). Mixed logistic regression results indicated that calves aged 15–21 days were more likely to be Cryptosporidium-positive. The risk of being positive was also significantly higher in herds from Central Sardinia and in farms using non-slatted flooring. In addition, the application of disinfectants and milk replacers was significantly associated with higher Cryptosporidium prevalence. In contrast, the risk of being positive was significantly reduced in halofuginone-treated calves. Our results reveal that a significant percentage of suckling calves are carriers of zoonotic subtypes of C. parvum. Thus, both healthy and diarrhoeic calves younger than 1 month may represent a risk for the transmission of cryptosporidiosis in humans and animals. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00436-018-6000-x) contains supplementary material, which is available to authorized users.


title: Sublingual immunization with recombinant adenovirus encoding SARS-CoV spike protein induces systemic and mucosal immunity without redirection of the virus to the brain

text: BACKGROUND: Sublingual (s.l.) administration of soluble protein antigens, inactivated viruses, or virus-like particles has been shown to induce broad immune responses in mucosal and extra-mucosal tissues. Recombinant replication-defective adenovirus vectors (rADVs) infect mucosa surface and therefore can serve as a mucosal antigen delivery vehicle. In this study we examined whether s.l. immunization with rADV encoding spike protein (S) (rADV-S) of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) induces protective immunity against SARS-CoV and could serve as a safe mucosal route for delivery of rADV. RESULTS: Here, we show that s.l. administration of rADV-S induced serum SARS-CoV neutralizing and airway IgA antibodies in mice. These antibody responses are comparable to those induced by intranasal (i.n.) administration. In addition, s.l. immunization induced antigen-specific CD8(+) T cell responses in the lungs that are superior to those induced by intramuscular immunization. Importantly, unlike i.n. administration, s.l. immunization with rADV did not redirect the rADV vector to the olfactory bulb. CONCLUSION: Our study indicates that s.l. immunization with rADV-S is safe and effective in induction of a broad spectrum of immune responses and presumably protection against infection with SARS-CoV.


title: Application of the LAMP Assay as a Diagnostic Technique for Rapid Identification of Thrips tabaci (Thysanoptera: Thripidae)

text: Rapid and accurate identification of potentially invasive taxa that may cause high economic losses or environmental damage is of critical importance. The onion thrips, Thrips tabaci Lindeman, ranks as one of the world’s most destructive agricultural pests and commonly found in imported agricultural products and field samples, but is prone to undetected transport because of its minute size as well as cryptic behavior. Although traditional taxonomic methods are pretty useful in straightforward assignment of specimens to the genus Thrips , identification in the species level is much more difficult and requires expertise, knowledge, and experience. Furthermore, it is often difficult or impossible to identify or distinguish this species from other thrips by using material from other stages of development. Based on the foregoings, use of a molecular technique known as loop-mediated isothermal amplification (LAMP) as a rapid and robust alternative species diagnostic tool would be valuable. In this study, a relatively quick and simple method was used to detect the presence of onion thrips DNA rapidly and discriminate it from other species, by using material from different stages of development. Not only LAMP itself required less than 1 h to complete but also amounts of DNA as little as that recovered from a single specimen were adequate for the detection. Another advantage of this identification system is that nonspecialists will be able to make faster and cheaper identifications.


title: Molecular Detection of Circovirus and Adenovirus in Feces of Fur Seals (Arctocephalus spp.)

text: In some regions, little is known about exposure to viruses in coastal marine mammals. The present study aimed to detect viral RNA or DNA in 23 free-ranging fur seals on the northern coastline of Rio Grande do Sul State, Brazil. Polymerase chain reaction was used to detect nucleic acids of circoviruses, adenoviruses, morbilliviruses, vesiviruses, and coronaviruses in the feces from twenty-one South American fur seals (Arctocephalus australis) and two Subantarctic fur seals (A. tropicalis). Adenovirus DNA fragments were detected in two South American fur seals; nucleotide sequences of these fragments revealed a high degree of similarity to human adenovirus type C. Circovirus DNA fragments were detected in six animals of the same species. Two were phylogenetically similar to the Circovirus genus, whereas the other four nucleotide fragments showed no similarity to any of the known genera within the family Circoviridae. RNA fragments indicating the presence of coronavirus, vesivirus, and morbillivirus were not detected. These findings suggest that adenoviruses and circoviruses are circulating in fur seal populations found along the coast of Rio Grande do Sul State, Brazil.


title: Introduction: microbes, networks, knowledge—disease ecology and emerging infectious diseases in time of COVID-19

text: This is an introduction to the topical collection Microbes, Networks, Knowledge: Disease Ecology in the twentieth Century, based on a workshop held at Queen Mary, University London on July 6–7 2016. More than twenty years ago, historian of science and medicine Andrew Mendelsohn asked, “Where did the modern, ecological understanding of epidemic disease come from?” Moving beyond Mendelsohn’s answer, this collection of new essays considers the global history of disease ecology in the past century and shows how epidemics and pandemics have made “microbes complex”.


title: Rapid redistribution of Golgi proteins into the ER in cells treated with brefeldin A: Evidence for membrane cycling from Golgi to ER

text: Abstract In cells treated with brefeldin A (BFA), movement of newly synthesized membrane proteins from the endoplasmic reticulum (ER) to the Golgi apparatus was blocked. Surprisingly, the glycoproteins retained in the ER were rapidly processed by cis/medial Golgi enzymes but not by trans Golgi enzymes. An explanation for these observations was provided from morphological studies at both the light and electron microscopic levels using markers for the cis/medial and trans Golgi. They revealed a rapid and dramatic redistribution to the ER of components of the cis/medial but not the trans Golgi in response to treatment with BFA. Upon removal of BFA, the morphology of the Golgi apparatus was rapidly reestablished and proteins normally transported out of the ER were efficiently and rapidly sorted to their final destinations. These results suggest that BFA disrupts a dynamic membrane-recycling pathway between the ER and cis/medial Golgi, effectively blocking membrane transport out of but not back to the ER.


title: Methodologies for measuring travelers' risk perception of infectious diseases: A systematic review

text: Summary Numerous studies in the past have stressed the importance of travelers' psychology and perception in the implementation of preventive measures. The aim of this systematic review was to identify the methodologies used in studies reporting on travelers' risk perception of infectious diseases. A systematic search for relevant literature was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. There were 39 studies identified. In 35 of 39 studies, the methodology used was that of a knowledge, attitude and practice (KAP) survey based on questionnaires. One study used a combination of questionnaires and a visual psychometric measuring instrument called the ‘pictorial representation of illness and self-measurement” or PRISM. One study used a self-representation model (SRM) method. Two studies measured psychosocial factors. Valuable information was obtained from KAP surveys showing an overall lack of knowledge among travelers about the most frequent travel-associated infections and associated preventive measures. This methodological approach however, is mainly descriptive, addressing knowledge, attitudes, and practices separately and lacking an examination of the interrelationships between these three components. Another limitation of the KAP method is underestimating psychosocial variables that have proved influential in health related behaviors, including perceived benefits and costs of preventive measures, perceived social pressure, perceived personal control, unrealistic optimism and risk propensity. Future risk perception studies in travel medicine should consider psychosocial variables with inferential and multivariate statistical analyses. The use of implicit measurements of attitudes could also provide new insights in the field of travelers’ risk perception of travel-associated infectious diseases.


title: Dissolution Advantage of Nitazoxanide Cocrystals in the Presence of Cellulosic Polymers

text: The effect of hydroxypropyl methylcellulose (HPMC) and methylcellulose (Methocel(®) 60 HG) on the dissolution behavior of two cocrystals derived from nitazoxanide (NTZ), viz., nitazoxanide-glutaric acid (NTZ-GLU, 1:1) and nitazoxanide-succinic acid (NTZ-SUC, 2:1), was explored. Powder dissolution experiments under non-sink conditions showed similar dissolution profiles for the cocrystals and pure NTZ. However, pre-dissolved cellulosic polymer in the phosphate dissolution medium (pH 7.5) modified the dissolution profile of NTZ when starting from the cocrystals, achieving transient drug supersaturation. Subsequent dissolution studies under sink conditions of polymer-based pharmaceutical powder formulations with NTZ-SUC cocrystals gave a significant improvement of the apparent solubility of NTZ when compared with analogous formulations of pure NTZ and the physical mixture of NTZ and SUC. Scanning electron microscopy and powder X-ray diffraction analysis of samples recovered after the powder dissolution studies showed that the cocrystals undergo fast dissolution, drug supersaturation and precipitation both in the absence and presence of polymer, suggesting that the solubilization enhancement is due to polymer-induced delay of nucleation and crystal growth of the less soluble NTZ form. The study demonstrates that the incorporation of an appropriate excipient in adequate concentration can be a key factor for inducing and maintaining the solubilization of poorly soluble drugs starting from co-crystallized solid forms. In such a way, cocrystals can be suitable for the development of solid dosage forms with improved bioavailability and efficacy in the treatment of important parasitic and viral diseases, among others.


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title: A review of feline infectious peritonitis virus infection: 1963–2008


title: Prevalence of malnutrition and analysis of related factors in elderly patients with COVID-19 in Wuhan, China

text: BACKGROUND/OBJECTIVES: To evaluate the prevalence of malnutrition and its related factors in elderly patients with COVID-19 in Wuhan, China. SUBJECTS/METHODS: In a cross-sectional study, we evaluated the nutritional status of elderly inpatients with COVID-19 using the Mini Nutritional Assessment (MNA). Based on MNA scores, patients were divided into non-malnutrition group (MNA ≥ 24), the group with risk of malnutrition (MNA 17–23.5) and malnutrition group (MNA score < 17). Regression analysis was conducted to screen for risk factors for malnutrition. RESULTS: A total of 182 patients were included in the study, of which 27.5% were in the group with malnutrition risk and 52.7% were in the malnutrition group. There were statistical differences in the incidence of comorbid diabetes mellitus, body mass index (BMI), calf circumference,albumin, hemoglobin, and lymphocyte counts among the three groups. Further regression analysis suggested that combined diabetes, low calf circumference, and low albumin were independent risk factors for malnutrition. CONCLUSIONS: The prevalence of malnutrition in elderly patients with COVID-19 was high, and nutritional support should be strengthened during treatment, especially for those with diabetes mellitus, low calf circumference, or low albumin.


title: Urban-Rural Disparity in Helicobacter Pylori Infection–Related Upper Gastrointestinal Cancer in China and the Decreasing Trend in Parallel with Socioeconomic Development and Urbanization in an Endemic Area

text: Abstract Background Globally China has the largest urban-rural disparity in socioeconomic development, and the urban-rural difference in upper gastrointestinal cancer (UGIC) is similar to the difference between developed and developing countries. Objectives To describe urban-rural disparity in UGIC and to emphasize prevention by socioeconomic development and urbanization in China. Methods Age-standardized incidence rates (ASRs) of cancers in 2012 were compared between urban Shijiazhuang city and rural Shexian County, and trends from 2000-2015 in Shexian County were analyzed. Findings Compared with urban Shijiazhuang city, the ASR of gastroesophageal cancers in rural Shexian County was 5.3 times higher in men (234.1 vs 44.2/100,000, P < .01) and 9.1 times higher in women (107.7 vs 11.8/100,000, P < .01). This rural-urban disparity in UGIC is associated with differences in socioeconomic development in annual gross domestic product (GDP) per capita of US$2700 vs US$6965, in urbanization rate of 48% vs 100%, and in adult Helicobacter pylori infection prevalence of 75% vs 50%. From 2000-2015, the GDP per capita in Shexian County increased from US$860 to US$3000, urbanization rate increased from 22.4% to 54.8%, and prevalence of H pylori infection among 3- to 10-year-old children decreased from 60% to 46.1% (P < .01). Meanwhile, the biennial ASR of esophagogastric cancer decreased 42% in men, from 313.5 to 182.1 per 100,000 (P < .01), and 57% in women, from 188.6 to 80.4 per 100,000 (P = .00). However, lung, colorectal, and gallbladder cancers and leukemia in both sexes and breast, ovary, thyroid, and kidney cancer in women increased significantly. Despite this offset, ASR of all cancers combined decreased 25% in men (from 378.2 to 283.0/100,000, P = .00) and 19% in women (from 238.5 to 193.6/100,000, P = .00). Conclusions Urban-rural disparity in UGIC is related to inequity in socioeconomic development. Economic growth and urbanization is effective for prevention in endemic regions in China and should be a policy priority.


title: The rippled newsvendor: A new inventory framework for modelling supply chain risk severity in the presence of risk propagation

text: How should managers take into account the propagation of supply chain disruptions and risks (i.e. the ripple effect) when they design their inventory policies? For over 60 years, various extensions and applications to the popular newsvendor model have been suggested, where cost/profit are often the focal objective. We propose a new version of the traditional single-period newsvendor model - the ”Rippled Newsvendor” - with supply chain severity (i.e. risk propagation) as the primary objective while taking into account network structure. Our model considers exogenous and endogenous risk(s) of disruption while exploring the tension between under-supply and ”wear-and-tear” (i.e system breakdown). To model the intricacies of this trade-off whilst minimizing the potential spread of risk, we leverage a Bayesian Network whereby the conditional probability distributions are functions of the inventory ordering decisions. We use a simulation study to understand the nature of our objective function as well as to gain insight into the potential optimal ordering policies of this new model. Furthermore, the simulation seeks to understand how the various factors in our system impact total risk severity, and if they do so in different ways. Our simulations indicate that local exogenous risk is of greater importance than non-local exogenous risk. Furthermore, we show that the type of risk, as well as the structural characteristics of the supply chain and inventory system, impact risk severity differently.


title: Unique and Conserved Features of Genome and Proteome of SARS-coronavirus, an Early Split-off From the Coronavirus Group 2 Lineage

text: Abstract The genome organization and expression strategy of the newly identified severe acute respiratory syndrome coronavirus (SARS-CoV) were predicted using recently published genome sequences. Fourteen putative open reading frames were identified, 12 of which were predicted to be expressed from a nested set of eight subgenomic mRNAs. The synthesis of these mRNAs in SARS-CoV-infected cells was confirmed experimentally. The 4382- and 7073 amino acid residue SARS-CoV replicase polyproteins are predicted to be cleaved into 16 subunits by two viral proteinases (bringing the total number of SARS-CoV proteins to 28). A phylogenetic analysis of the replicase gene, using a distantly related torovirus as an outgroup, demonstrated that, despite a number of unique features, SARS-CoV is most closely related to group 2 coronaviruses. Distant homologs of cellular RNA processing enzymes were identified in group 2 coronaviruses, with four of them being conserved in SARS-CoV. These newly recognized viral enzymes place the mechanism of coronavirus RNA synthesis in a completely new perspective. Furthermore, together with previously described viral enzymes, they will be important targets for the design of antiviral strategies aimed at controlling the further spread of SARS-CoV.


title: Human rhinovirus C: Age, season, and lower respiratory illness over the past 3 decades

text: BACKGROUND: Human rhinoviruses (HRVs) cause common colds, and the recently discovered HRV-C is increasingly associated with lower respiratory illness among populations such as children and asthmatic patients. OBJECTIVE: To determine how HRV-C is associated with respiratory illness and to evaluate changes in prevalence and species over 2 decades. METHODS: A prospective study of children younger than 5 years was performed at the Vanderbilt Vaccine Clinic over a 21-year period. Nasal-wash specimens from children presenting with upper or lower respiratory illness at acute care visits were tested for HRV and HRV-positives genotyped. Demographic and clinical features were compared between children with or without HRV, and with different HRV species. RESULTS: HRV was detected in 190 of 527 (36%) specimens from a population of 2009 children from 1982 through 2003. Of these, 36% were HRV-C. Age (P = .039) and month of illness (P <.001) were associated with HRV infection and HRV species. HRV-C was significantly associated with lower respiratory illness, compared with HRV-A (P = .014). HRV-A and HRV-C prevalence fluctuated throughout the 21-year period; HRV-C was more prevalent during winter (P = .058). CONCLUSIONS: HRV-C is not a new virus but has been significantly associated with childhood lower respiratory illness in this population for several decades. Temporal changes in virus prevalence occur, and season may predict virus species. Our findings have implications for diagnostic, preventive, and treatment strategies due to the variation in disease season and severity based on species of HRV infection.


title: Bovine respiratory syncytial virus seroprevalence and risk factors in non-vaccinated dairy cattle herds in Brazil

text: BACKGROUND: The cattle industry is one of the most important Brazilian agribusiness sectors and is a strong contributor to the national economy. Annually about 44.6 million calves are bred, which makes the optimal management of these animals extremely important. Several diseases can affect the initial stages of the bovine production chain, being the bovine respiratory syncytial virus (BRSV) one of the most relevant pathogens. This study aimed to characterize the epidemiology of BRSV infection in dairy cattle herds of São Paulo State, Brazil, using serological and risk factors analyses. For that, 1243 blood samples were collected of animals from 26 farms and a questionnaire about possible risk factors for BRSV prevalence was performed. The obtained blood sera were analyzed using virus neutralization test (VNT). RESULTS: VNT results showed high BRSV prevalence in dairy cattle herds, reaching 79.5% of seropositivity. The BRSV seroprevalence among studied farms ranged from 40 to 100%. The analysis of risk factors indicated that the age group and the occurrence of coinfection with bovine herpesvirus 1 (BoHV-1) and bovine viral diarrhea virus 1 (BVDV-1) should be associated with a higher prevalence of BRSV, while natural suckling was considered a protective factor. CONCLUSIONS: The study showed that adult animals over 1 year old are an important risk factor for the high seroprevalence of BRSV in herds. The high BRSV prevalence associated with BoHV-1 and BVDV-1 suggests that biosecurity measures should be applied in order to reduce viral dissemination. Additionally, the natural suckling may be an important management to protect calves from high BRSV seroprevalence.


title: Chapter 18 Viral Epidemiology Tracking Viruses with Smartphones and Social Media

text: Abstract The science of epidemiology has been developed over the last 200years, using traditional methods to describe the distribution of diseases by person, place, and time. However, in the last several decades, a new set of technologies has become available, based on the methods of computer sciences, systems biology, and the extraordinary powers of the Internet. Technological and analytical advances can enhance traditional epidemiological methods to study the emergence, epidemiology, and transmission dynamics of viruses and associated diseases. Social media are increasingly used to detect the emergence and geographic spread of viral disease outbreaks. Large-scale population movement can be estimated using satellite imagery and mobile phone use, and fine-scale population movement can be tracked using global positioning system loggers, allowing estimation of transmission pathways and contact patterns at different spatial scales. Advances in genomic sequencing and bioinformatics permit more accurate determination of viral evolution and the construction of transmission networks, also at different spatial and temporal scales. Phylodynamics links evolutionary and epidemiological processes to better understand viral transmission patterns. More complex and realistic mathematical models of virus transmission within human and animal populations, including detailed agent-based models, are increasingly used to predict transmission patterns and the impact of control interventions such as vaccination and quarantine. In this chapter, we will briefly review traditional epidemiological methods and then describe the new technologies with some examples of their application.


title: Identification of protective T-cell antigens for smallpox vaccines

text: Abstract E3L is an immediate-early protein of vaccinia virus that is detected within 0.5 hours of infection, potentially before the many immune evasion genes of vaccinia can exert their protective effects. E3L is highly conserved among orthopoxviruses and hence could provide important protective T-cell epitopes that should be retained in any subunit or attenuated vaccine. We have therefore evaluated the immunogenicity of E3L in healthy VV vaccinated donors. Peripheral blood mononuclear cells from healthy volunteers (n=13) who had previously received a smallpox vaccine (Dryvax®) were activated and expanded using overlapping E3L peptides and their function, specificity and anti-viral activity was analyzed. E3L-specific T-cells were expanded from 7 of 12 (58.3%) vaccinated healthy donors. 25% of these produced CD8+ T-cell responses and 87.5% produced CD4+ T-cells. We identified epitopes restricted by HLA-B35 and HLA-DR15. E3L-specific T-cells killed peptide-loaded target cells as well as vaccinia-infected cells but only CD8+ T-cells could prevent the spread of infectious virus in virus inhibition assays. The epitopes recognized by E3L-specific T-cells were shared with monkeypox and although there was a single amino acid change in the variola epitope homolog, it was recognized by vaccinia-specific T-cells. Therefore it might be important to include E3L in any deletion mutant or subunit vaccine and E3L could provide a useful antigen to monitor protective immunity in humans.


title: The Role of Clinical Virology Laboratory and the Clinical Virology Laboratorian in Ensuring Effective Surveillance for Influenza and Other Respiratory Viruses: Points to Consider and Pitfalls to Avoid

text: Influenza and respiratory viruses have a global impact on public health. Clinical virology laboratories and laboratorians play an important role in not only the diagnosis but also the surveillance of these pathogens. Surveillance for influenza and other respiratory pathogens is important, as it informs public health decision making in terms of influenza vaccine and antiviral effectiveness, informs clinicians and public health practitioners about the pathogenicity of specific viral strains, guides clinical practice, and supports laboratory panning activities. Key background issues include the following: the fact that the laboratory is only one of several data providers to a surveillance system, the biologic nature of influenza and respiratory viruses and the laboratory needs to keep up to date on the diagnosis of these agents, the need for laboratorians to be involved in case definition development, the impact of push and pull data flow models on laboratory resources, and the fact that laboratories may be asked to provide more than just test results to surveillance programs. This review also identifies some key issues or questions that arise during the pre-analytic, analytic, and post-analytic phases that could impact on the ability of the laboratory to link to surveillance programs. Finally, issues surrounding virus characterization programs and how they link to surveillance programs are identified and discussed.


title: A predictive nomogram for predicting improved clinical outcome probability in patients with COVID-19 in zhejiang province, china

text: The aim of this research was to develop a quantitative method for clinicians to predict the probability of improved prognosis in patients with coronavirus disease 2019 (COVID-19). Data on 104 patients admitted to hospital with laboratory-confirmed COVID-19 infection from 10 January 2020 to 26 February 2020 were collected. Clinical information and laboratory findings were collected and compared between the outcomes of improved patients and non-improved patients. The least absolute shrinkage and selection operator (LASSO) logistics regression model and two-way stepwise strategy in the multivariate logistics regression model were used to select prognostic factors for predicting clinical outcomes in COVID-19 patients. The concordance index (C-index) was used to assess the discrimination of the model, and internal validation was performed through bootstrap resampling. A novel predictive nomogram was constructed by incorporating these features. Of the 104 patients included in the study (median age 55 years), 75 (72.1%) had improved short-term outcomes, while 29 (27.9%) showed no signs of improvement. There were numerous differences in clinical characteristics and laboratory findings between patients with improved outcomes and patients without improved outcomes. After a multi-step screening process, prognostic factors were selected and incorporated into the nomogram construction, including immunoglobulin A (IgA), C-reactive protein (CRP), creatine kinase (CK), Acute Physiology and Chronic Health Evaluation II (APACHE II), and interaction between CK and APACHE II. The C-index of our model was 0.962 (95% confidence interval (CI), 0.931–0.993) and still reached a high value of 0.948 through bootstrapping validation. A predictive nomogram we further established showed close performance compared with the ideal model on the calibration plot and was clinically practical according to the decision curve and clinical impact curve. The nomogram we constructed is useful for clinicians to predict improved clinical outcome probability for each COVID-19 patient, which may facilitate personalized counselling and treatment.


“COVID-19 Leading to Acute Encephalopathy in a Heart Transplant Patient”


title: Energy Return on Investment (EROI) and Life Cycle Analysis (LCA) of biofuels in Ecuador

text: In Ecuador, the net energy contribution of biofuels is unknown or unnoticed. To address this issue, we determined the Energy Return on Investment (EROI) for bioethanol and biodiesel. The selection of raw materials relied on their productive capacity, export and import records, and historical yields. Consequently, the scope included three raw materials for ethanol (sugar cane, corn, and forest residues) and four for biodiesel (African palm, pinion, bovine fat, and swine fat). Using a method based on the Life Cycle Analysis (LCA) of each biofuel, we assessed the entire production chain through statistical processing of primary and secondary information. Then we calculated the calorific values in the laboratory, compared energy inputs/outputs, and finally obtained the energetic returns. EROIs for bioethanol were: 1.797 for sugarcane, 1.040 for corn, and 0.739 for wood. The results for biodiesel were: 3.052 for African palm, 2.743 for pinion, 2.187 for bovine fat, and 2.891 for swine fat. These values suggest feasibility only for sugarcane in the case of ethanol. In contrast, biodiesel has better prospects because all the feedstocks analyzed had EROIs higher than two. Nevertheless, biodiesel is not available for trading in Ecuador because energy policy has overlooked systems based on higher energy return. Future studies should consider more comprehensive variables such as climate change, land use, and water management.


title: Increasing Access to Care: Telehealth During COVID-19

text: The COVID-19 public health emergency has amplified both the potential value and the challenges with health care providers deploying telehealth solutions. As people across the country find ways to stay at home, telehealth preserves an opportunity to obtain necessary healthcare services. Further, telehealth can help individuals avoid COVID-19 infection, free up hospital beds and other resources for those patients most in need and prevent infected individuals from spreading that infection. Federal and state regulators have recognized this potential of telehealth and have quickly changed a variety of laws and regulations to enable health care providers to deploy solutions quickly. These changes can provide lasting benefits for the use of telehealth well after the current crisis. However, to best realize telehealth’s benefits further legal and regulatory action are necessary. Specifically, lawmakers and regulators should focus on six areas: reimbursement, privacy/cybersecurity, liability, licensure, technology access, and AI.


title: Vergesellschaftung unter Ansteckenden – für eine Körpergeschichte der Seuche

text: This paper is part of Forum COVID-19: Perspectives in the Humanities and Social Sciences. Being a “trauma of mankind” epidemics have been a major subject of historical research for a long time and regarding every historical period. Recurring to the concept of Rudolf Schlögl (“Vergesellschaftung unter Anwesenden”) my proposal is to research epidemics as a history of the communicating body and thus including the contagium as part of this communication.


title: Antiseptic properties of two calix[4]arenes derivatives on the human coronavirus 229E

text: Abstract Facing the lack in specific antiviral treatment, it is necessary to develop new means of prevention. In the case of the Coronaviridae this family is now recognized as including potent human pathogens causing upper and lower respiratory tract infections as well as nosocomial ones. Within the purpose of developing new antiseptics molecules, the antiseptic virucidal activity of two calix[4]arene derivatives, the tetra-para-sulfonato-calix[4]arene (C[4]S) and the 1,3-bis(bithiazolyl)-tetra-para-sulfonato-calix[4]arene (C[4]S-BTZ) were evaluated toward the human coronavirus 229E (HCoV 229E). Comparing these results with some obtained previously with chlorhexidine and hexamidine, (i) these two calixarenes did not show any cytotoxicity contrary to chlorhexidine and hexamidine, (ii) C[4]S showed as did hexamidine, a very weak activity against HCoV 229E, and (iii) the C[4]S-BTZ showed a stronger activity than chlorhexidine, i.e. 2.7 and 1.4log10 reduction in viral titer after 5min of contact with 10−3 molL−1 solutions of C[4]S-BTZ and chlorhexidine, respectively. Thus, the C[4]S-BTZ appeared as a promising virucidal (antiseptic) molecule.


title: Stable Occupancy of the Crimean-Congo Hemorrhagic Fever Virus-Encoded Deubiquitinase Blocks Viral Infection

text: Crimean-Congo hemorrhagic fever virus (CCHFV) infection can result in a severe hemorrhagic syndrome for which there are no antiviral interventions available to date. Certain RNA viruses, such as CCHFV, encode cysteine proteases of the ovarian tumor (OTU) family that antagonize interferon (IFN) production by deconjugating ubiquitin (Ub). The OTU of CCHFV, a negative-strand RNA virus, is dispensable for replication of the viral genome, despite being part of the large viral RNA polymerase. Here, we show that mutations that prevent binding of the OTU to cellular ubiquitin are required for the generation of recombinant CCHFV containing a mutated catalytic cysteine. Similarly, the high-affinity binding of a synthetic ubiquitin variant (UbV-CC4) to CCHFV OTU strongly inhibits viral growth. UbV-CC4 inhibits CCHFV infection even in the absence of intact IFN signaling, suggesting that its antiviral activity is not due to blocking the OTU’s immunosuppressive function. Instead, the prolonged occupancy of the OTU with UbV-CC4 directly targets viral replication by interfering with CCHFV RNA synthesis. Together, our data provide mechanistic details supporting the development of antivirals targeting viral OTUs.


COVID-19—What we know and what we need to know: There are more questions than answers


docid: mjdqrgjr

title: Recent advances and perspectives of nucleic acid detection for coronavirus

text: The recent pneumonia outbreak caused by a novel coronavirus (SARS-CoV-2) is posing a great threat to global public health. Therefore, rapid and accurate identification of pathogenic viruses plays a vital role in selecting appropriate treatments, saving people’s lives and preventing epidemics. It is important to establish a quick standard diagnostic test for the detection of the infectious disease (COVID-19) to prevent subsequent secondary spread. Polymerase chain reaction (PCR) is regarded as a gold standard test for the molecular diagnosis of viral and bacterial infections with high sensitivity and specificity. Isothermal nucleic acid amplification is considered to be a highly promising candidate method due to its fundamental advantage in quick procedure time at constant temperature without thermocycler operation. A variety of improved or new approaches also have been developed. This review summarizes the currently available detection methods for coronavirus nucleic acid. It is anticipated that this will assist researchers and clinicians in developing better techniques for timely and effective detection of coronavirus infection.


title: Under‐folded proteins: Conformational ensembles and their roles in protein folding, function, and pathogenesis

text: For decades, protein function was intimately linked to the presence of a unique, aperiodic crystal‐like structure in a functional protein. The two only places for conformational ensembles of under‐folded (or partially folded) protein forms in this picture were either the end points of the protein denaturation processes or transiently populated folding intermediates. Recent years witnessed dramatic change in this perception and conformational ensembles, which the under‐folded proteins are, have moved from the shadow. Accumulated to date data suggest that a protein can exist in at least three global forms–functional and folded, functional and intrinsically disordered (nonfolded), and nonfunctional and misfolded/aggregated. Under‐folded protein states are crucial for each of these forms, serving as important folding intermediates of ordered proteins, or as functional states of intrinsically disordered proteins (IDPs) and IDP regions (IDPRs), or as pathology triggers of misfolded proteins. Based on these observations, conformational ensembles of under‐folded proteins can be classified as transient (folding and misfolding intermediates) and permanent (IDPs and stable misfolded proteins). Permanently under‐folded proteins can further be split into intentionally designed (IDPs and IDPRs) and unintentionally designed (misfolded proteins). Although intrinsic flexibility, dynamics, and pliability are crucial for all under‐folded proteins, the different categories of under‐foldedness are differently encoded in protein amino acid sequences. © 2013 Wiley Periodicals, Inc. Biopolymers 99: 870–887, 2013.


title: Musculoskeletal and Neurologic Diseases

text: Ferrets may exhibit neurologic signs as a result of various conditions that may be of nervous or muscular origin. Neurologic examination follows the same principles as in small animal medicine. One of the main defect that may be screened during clinical examination is deafness. Congenital deafness in ferrets is associated with coat color patterns such as white markings and premature graying.In this species, paresis is a common presentation and may reflect a generalized weakness. Spinal disorder, intervertebral disk disease, and neoplasia are among the differential diagnosis. Diagnostic exams usually include advance diagnostic imaging such as CT-scan associated with myelography. Seizure is usually associated with hypoglycemia and insulinoma, but other causes such as hypocalcemia or intracranial disorders have been described. Ferrets are sensitive to various neurotropic infectious disease such as rabies, distemper, aleutian disease, or systemic coronavirus. Finally, muscular disorder such as disseminated idiopathic myofasciitis and myasthenia gravis have been recently described, and potential treatments have been intended.


docid: xtkmwgya

title: Distinct Structural Elements and Internal Entry of Ribosomes in mRNA3 Encoded by Infectious Bronchitis Virus

text: Abstract Infectious bronchitis virus (IBV) mRNA3 encodes three small proteins, 3a, 3b, and 3c, at its 5′ end. Recently, it was demonstrated that initiation of protein 3c is dependent on the upstream sequence. Monte Carlo simulations of RNA folding in this tricistronic mRNA3 indicate that a highly significant folding region occurs prior to the initiator AUG of 3c. The unusual folding region (UFR) of 265 nucleotides (nt) contains the coding sequences of proteins 3a and 3b. Details of the structural analyses show that five highly significant RNA stem-loops in the UFR can be modeled into a compact superstructure by the interaction of two predicted pseudoknot structures. The folded superstructure comprising nt 44 to 330, with additional 22 nt downstream from this UFR, is suggested to serve as a ribosome landing pad (or an internal ribosomal entry site) in the cap-independent translation of the 3c of IBV. Intriguingly, the proposed structural motif of this coronavirus shares structural features similar to those proposed in a number of picornavirus mRNAs. Based on the common structural features, a plausible base pairing model between mRNA3 and 18 S rRNA is suggested, which is consistent with a general mechanism for regulation of internal initiation described in many picornaviruses.


title: Porcine deltacoronavirus (PDCoV) infection suppresses RIG-I-mediated interferon-β production

text: Abstract Porcine deltacoronavirus (PDCoV), an emerging animal coronavirus causing enteric disease in pigs, belongs to the newly identified Deltacoronavirus genus in the Coronaviridae family. Although extensive studies have been carried out to investigate the regulation of interferon (IFN) responses by alphacoronaviruses, betacoronaviruses, and gammacoronaviruses, little is known about this process during deltacoronavirus infection. In this study, we found that PDCoV infection fails to induce, and even remarkably inhibits, Sendai virus- or poly(I: C)-induced IFN-β production by impeding the activation of transcription factors NF-κB and IRF3. We also found that PDCoV infection significantly suppresses the activation of IFN-β promoter stimulated by IRF3 or its upstream molecules (RIG-I, MDA5, IPS-1, TBK1, IKKε) in the RIG-I signaling pathway, but does not counteract its activation by the constitutively active mutant of IRF3 (IRF3–5D). Taken together, our results demonstrate that PDCoV infection suppresses RIG-I-mediated IFN signaling pathway, providing a better understanding of the PDCoV immune evasion strategy.


docid: qicchvhf

title: Interactions between M protein and other structural proteins of severe, acute respiratory syndrome-associated coronavirus

text: Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) structural proteins (S, E, M, and NC) localize in different subcellular positions when expressed individually. However, SARS-CoV M protein is co-localized almost entirely with S, E, or NC protein when co-expressed in the cells. On the other hand, only partial co-localization was observed when S and E, S and NC, or E and NC were co-expressed in the cells. Interactions between SARS-CoV M and other structural proteins but not interactions between S and E, S and NC, or E and NC were further demonstrated by co-immunoprecipitation assay. These results indicate that SARS-CoV M protein, similar to the M proteins of other coronaviruses, plays a pivotal role in virus assembly. The cytoplasmic C-terminus domain of SARS-CoV M protein was responsible for binding to NC protein. Multiple regions of M protein interacted with E and S proteins. A model for the interactions between SARS-CoV M protein and other structural proteins is proposed. This study helps us better understand protein-protein interactions during viral assembly of SARS-CoV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11373-008-9278-3) contains supplementary material, which is available to authorized users.


Herbs that might be effective for the management of COVID-19: A bioinformatics analysis on anti-tyrosine kinase property


title: Cyclodextrins in non-viral gene delivery

text: Abstract Cyclodextrins (CDs) are naturally occurring cyclic oligosaccharides. They consist of (α-1,4)-linked glucose units, and possess a basket-shaped topology with an “inner–outer” amphiphilic character. Over the years, substantial efforts have been undertaken to investigate the possible use of CDs in drug delivery and controlled drug release, yet the potential of CDs in gene delivery has received comparatively less discussion in the literature. In this article, we will first discuss the properties of CDs for gene delivery, followed by a synopsis of the use of CDs in development and modification of non-viral gene carriers. Finally, areas that are noteworthy in CD-based gene delivery will be highlighted for future research. Due to the application prospects of CDs, it is anticipated that CDs will continue to emerge as an important tool for vector development, and will play significant roles in facilitating non-viral gene delivery in the forthcoming decades.


title: Extraordinary GU-rich single-strand RNA identified from SARS coronavirus contributes an excessive innate immune response

text: Abstract A dangerous cytokine storm occurs in the SARS involving in immune disorder, but many aspects of the pathogenetic mechanism remain obscure since its outbreak. To deeply reveal the interaction of host and SARS-CoV, based on the basic structural feature of pathogen-associated molecular pattern, we created a new bioinformatics method for searching potential pathogenic molecules and identified a set of SARS-CoV specific GU-rich ssRNA fragments with a high-density distribution in the genome. In vitro experiments, the result showed the representative SARS-CoV ssRNAs had powerful immunostimulatory activities to induce considerable level of pro-inflammatory cytokine TNF-a, IL-6 and IL-12 release via the TLR7 and TLR8, almost 2-fold higher than the strong stimulatory ssRNA40 that was found previously from other virus. Moreover, SARS-CoV ssRNA was able to cause acute lung injury in mice with a high mortality rate in vivo experiment. It suggests that SARS-CoV specific GU-rich ssRNA plays a very important role in the cytokine storm associated with a dysregulation of the innate immunity. This study not only presents new evidence about the immunopathologic damage caused by overactive inflammation during the SARS-CoV infection, but also provides a useful clue for a new therapeutic strategy.


title: Factors preventing materno-fetal transmission of SARS-CoV-2

text: Although many pregnant women have been infected by coronavirus, the presence of intrauterine vertical transmission has not been conclusively reported yet. What prevents this highly contagious virus from reaching the fetus? Is it only the presence of a strong placental barrier, or is it the natural absence of the some receptor that the viruses use for transmission? We, therefore, need to comprehensively understand the mechanism of action of the mammalian epithelial barriers located in two different organs with functional similarity. The barriers selected as potential targets by SARS-CoV-2 are the alveolo-capillary barrier (ACB), and the syncytio-capillary barrier (SCB). Caveolae are omega-shaped structures located on the cell membrane. They consist of caveolin-1 protein (Cav-1) and are involved in the internalisation of some viruses. By activating leukocytes and nuclear factor-κB, Cav-1 initiates inflammatory reactions. The presence of more than one Cav-1 binding sites on coronavirus is an important finding supporting the possible relationship between SARS-CoV-2-mediated lung injury. While the ACB cells express Cav-1 there is no caveolin expression in syncytiotrophoblasts. In this short review, we will try to explain our hypothesis that the lack of caveolin expression in the SCB is one of the most important physiological mechanisms that prevents vertical transmission of SARS-CoV-2. Since the physiological Cav-1 deficiency appears to prevent acute cell damage treatment algorithms could potentially be developed to block this pathway in the non-pregnant population affected by SARS-CoV-2.


docid: hhjpjucc

title: Chronic obstructive pulmonary disease

text: Summary Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow obstruction that is only partly reversible, inflammation in the airways, and systemic effects or comorbities. The main cause is smoking tobacco, but other factors have been identified. Several pathobiological processes interact on a complex background of genetic determinants, lung growth, and environmental stimuli. The disease is further aggravated by exacerbations, particularly in patients with severe disease, up to 78% of which are due to bacterial infections, viral infections, or both. Comorbidities include ischaemic heart disease, diabetes, and lung cancer. Bronchodilators constitute the mainstay of treatment: β2 agonists and long-acting anticholinergic agents are frequently used (the former often with inhaled corticosteroids). Besides improving symptoms, these treatments are also thought to lead to some degree of disease modification. Future research should be directed towards the development of agents that notably affect the course of disease.


title: Bilio-pancreatic endoscopy during COVID-19 pandemic

text: On 31 December 2019, the WHO China Country Office was informed of cases of pneumonia of unknown etiology detected in Wuhan (Hubei Province of China). In January 2020, a new coronavirus named SARS-CoV2 was isolated and, since that time, SARS-CoV2 related disease (COVID-19) rapidly spread all over the world becoming pandemic in March 2020. The COVID-19 outbreak dramatically affected the public-health and the health-care facilities organization. Bilio-pancreatic endoscopy is considered a high-risk procedure for cross-contamination and, even though it is not directly involved in COVID-19 diagnosis and management, its reorganization is crucial to guarantee high standards of care minimizing the risk of SARS-CoV2 transmission among patients and health-care providers. Bilio-pancreatic endoscopic procedures often require a short physical distance between the endoscopist and the patient for a long period of time, a frequent exchange of devices, the involvement of a large number of personnel, the use of complex endoscopes difficult to reprocess. On this basis, endoscopic units should take precautions with adjusted management of bilio-pancreatic endoscopy. The aim of this article is to discuss the approach to bilio-pancreatic endoscopy in the COVID-19 era with focus on diagnostic algorithms, indications, management of the endoscopic room, proper use of Personal Protective Equipment and correct reprocessing of instrumentation.


title: Treatment, outcomes and costs of asthma exacerbations in Chilean children: a prospective multicenter observational study

text: Abstract Objective To describe potential regional variations in therapies for severe asthma exacerbations in Chilean children and estimate the associated health expenditures. Methods Observational prospective cohort study in 14 hospitals over a one-year period. Children five years of age or older were eligible for inclusion. Days with oxygen supply and pharmacological treatments received were recorded from the clinical chart. A basic asthma hospitalization basket was defined in order to estimate the average hospitalization cost for a single patient. Six months after discharge, new visits to the Emergency Room (ER), use of systemic corticosteroids and adherence to the controller treatment were evaluated. Results 396 patients were enrolled. Patients from the public health system and from the north zone received significantly more days of oxygen, systemic corticosteroids and antibiotics. Great heterogeneity in antibiotic use among the participating hospitals was found, from 0 to 92.3% (ICC 0.34, 95% CI 0.16–0.52). The use of aminophylline, magnesium sulfate and ketamine varied from 0 to 36.4% between the different Pediatric Intensive Care Units (ICC 0.353, 95% CI 0.010–0.608). The average cost per inpatient was of $1910 USD. 290 patients (73.2%) completed the follow-up six months after discharge. 76 patients (26.2%) were not receiving any controller treatment and nearly a fourth had new ER visits and use of systemic corticosteroids due to new asthma exacerbations. Conclusions Considerable practice variation in asthma exacerbations treatment was found among the participating hospitals, highlighting the poor outcome of many patients after hospital discharge, with an important health cost.


La Dermatología Española en la era del COVID-19


title: The journey of remdesivir: from Ebola to COVID-19

text: Countries around the world are currently fighting the coronavirus disease 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a betacoronavirus, belonging to the same genus as severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV. Currently, there are no proven antiviral therapies for COVID-19. Numerous clinical trials have been initiated to identify an effective treatment. One leading candidate is remdesivir (GS-5734), a broad-spectrum antiviral that was initially developed for the treatment of Ebola virus (EBOV). Although remdesivir performed well in preclinical studies, it did not meet efficacy endpoints in a randomized trial conducted during an Ebola outbreak. Remdesivir holds promise for treating COVID-19 based on in vitro activity against SARS-CoV-2, uncontrolled clinical reports, and limited data from randomized trials. Overall, current data are insufficient to judge the efficacy of remdesivir for COVID-19, and the results of additional randomized studies are eagerly anticipated. In this narrative review, we provide an overview of Ebola and coronavirus outbreaks. We then summarize preclinical and clinical studies of remdesivir for Ebola and COVID-19.


title: Comparison of FilmArray Respiratory Panel and laboratory-developed real-time reverse transcription–polymerase chain reaction assays for respiratory virus detection

text: Abstract The FilmArray Respiratory Panel (Idaho Technology) is a highly multiplexed respiratory virus real-time polymerase chain reaction (PCR) assay. Eighty-four respiratory viruses identified by laboratory-developed real-time reverse transcription–PCR assays (LDA) or by viral cultures were mixed and tested by FilmArray to assess its performance. FilmArray identified 72 (90%) of 80 viruses also detected by LDA. Six of the 8 viruses not detected by FilmArray had PCR cycle threshold values >35. Compared to LDA, FilmArray showed comparable sensitivity when used to test serial dilutions of virus mixtures and good agreement with negative samples. With the use of 1 FilmArray instrument, 7 clinical samples could be analyzed and reported in an 8-h shift compared to 20 using LDA and 1 real-time detection instrument. While the FilmArray was rapid and easy to use, its low throughput and qualitative results may be a disadvantage in some clinical settings.


title: Molecular characteristic and pathogenicity analysis of a virulent recombinant avain infectious bronchitis virus isolated in China

text: ABSTRACT A virulent infectious bronchitis virus (IBV), designated as CK/CH/GD/QY16 (referred as QY16), was isolated from a diseased chicken farm in Guangdong province, China, in 2016. The complete genome of the strain was sequenced and analyzed. The results show that the genome of QY16 consists of 27,670 nucleotides, excluding poly (A) tail, and that its genome organization is 5’ UTR-1a-1b-S-3a-3b-E-M-4b-4c-5a-5b-N-6b-3’ UTR-poly (A) tail. Sequence comparison among QY16 and other IBV strains was conducted and its results demonstrate that the S1 gene of QY16 has the highest nucleotide sequence identity with that of 4/91, and the other part of its genome is highly similar to that of YX10. The results of the phylogenic analysis show that the entire genome of QY16 and most of the QY16 genes are located in the same cluster as those of YX10, except for the S1 gene which is located in the same cluster with that of 4/91. It has been further confirmed by the RDP and SimPlot analysis that QY16 is a recombinant strain deriving from YX10 (as the major parental sequence) and 4/91 (as the minor parental sequence), and that the recombination occurs in a region which includes the 3’-terminal 1b sequence (85 nt) and the 5’-terminal S1 protein gene sequence (1,466 nt). The results of the vaccination-challenge test suggest that QY16 is a nephropathogenic strain of IBV and that the vaccine strains–H120 and 4/91—cannot provide effective protection against it. These results indicate that the continuing evolution of IBV strains by genetic drift and genetic recombination may lead to IBV outbreaks even among the vaccinated chickens in China.


title: Need for integrative thinking to fight against emerging infectious diseases. Proceedings of the 5th seminar on emerging infectious diseases, March 22, 2016 – current trends and proposals

text: Abstract We present here the proceedings of the 5th seminar on emerging infectious diseases, held in Paris on March 22nd, 2016, with seven priority proposals that can be outlined as follows: encourage research on the prediction, screening and early detection of new risks of infection; develop research and surveillance concerning transmission of pathogens between animals and humans, with their reinforcement in particular in intertropical areas (“hot-spots”) via public support; pursue aid development and support in these areas of prevention and training for local health personnel, and foster risk awareness in the population; ensure adapted patient care in order to promote adherence to treatment and to epidemic propagation reduction measures; develop greater awareness and better education among politicians and healthcare providers, in order to ensure more adapted response to new types of crises; modify the logic of governance, drawing from all available modes of communication and incorporating new information-sharing tools; develop economic research on the fight against emerging infectious diseases, taking into account specific driving factors in order to create a balance between preventive and curative approaches.


title: Distancing Bonus Or Downscaling Loss? The Changing Livelihood of Us Online Workers in Times of COVID‐19

text: We draw on data from the Online Labour Index and interviews with freelancers in the United States securing work on online platforms, to illuminate effects of the COVID‐19 pandemic. The pandemic's global economic upheaval is shuttering shops and offices. Those able to do so are now working remotely from their homes. They join workers who have always been working remotely: freelancers who earn some or all of their income from projects secured via online labour platforms. Data allow us to sketch a first picture of how the initial months of the COVID‐19 pandemic have affected the livelihoods of online freelancers. The data shows online labour demand falling rapidly in early March 2020, but with an equally rapid recovery. We also find significant differences between countries and occupations. Data from interviews make clear jobs are increasingly scarce even as more people are creating profiles and seeking freelance work online.


title: Prevalence of enteric viruses among hospital patients with AIDS in Kinshasa, Zaire

text: Abstract Diarrhoea is the most common manifestation of acquired immunodeficiency syndrome (AIDS) in Africa. Numerous parasitic or bacterial agents have been implicated, but a pathogen-specific aetiology has not been found. Enteric viruses (i.e., rotavirus, small round structured viruses, coronavirus, and adenovirus) were detected by enzyme-linked immunosorbent assay or electron microscopy in faecal specimens of 17% of 198 consecutive adult admissions to a general medical ward of an urban hospital in Kinshasa, Zaire. Overall, 57% of patients were seropositive for infection with human immunodeficiency virus (HIV) 1; of these, 50% were classified as World Health Organization Aids stage IV. The prevalence of enteric viruses in stool specimens did not differ significantly between patients with and without HIV infection, and was not associated with acute or chronic diarrhoea, or constitutional symptoms. However, a trend (P = 0·14) towards greater frequency of virus in stools from patients in the lower 3 quintiles of the CD4/CD8 T cell ratio was seen. This trend approached statistical significance (P = 0·07) with stratification by HIV infection. Although we found no evidence in this population to support a major pathogenic role for these viruses alone in the enteropathy of AIDS, increased viral shedding was weakly associated with immunodeficiency.


title: Effect of TLR agonist on infections bronchitis virus replication and cytokine expression in embryonated chicken eggs

text: Abstract Avian infectious bronchitis (IB) is an acute, highly infectious and contagious viral disease of chickens caused by avian infectious bronchitis virus (IBV) belonging to the genus Coronavirus and family Coronaviridae. It can affect all age groups of birds. The toll-like receptors (TLRs) are a major class of innate immune pattern recognition receptors that have a key role in immune response and defense against various infections.The TLRs are essential for initiation of innate immune responses and in the development of adaptive immune responses. An in ovo model was employed to study the antiviral activity of TLR ligands (Pam3CSK4, LPS and CpG ODN) on replication of IBV. It was hypothesized that optimum dose and specific timing of TLR ligands may reduce viral load of IBV in specific pathogen free (SPF) embryonated chicken eggs (ECEs). Further, the mechanism involved in the TLR-mediated antiviral response in chorioallantoic membrane (CAM) of ECEs was investigated. The ECEs of 9–11 days old were treated with different doses (high, intermediate and low) of TLR-2 (Pam3CSK4), TLR-4 (LPS) and TLR-21 (CpG ODN) ligands. In addition, to know the timing of TLR ligand treatment, six time intervals were analyzed viz. 36, 24 and 12 h prior to infection, time of infection (co-administration of TLR ligands and avian IBV) and 12 and 24 h post-IBV infection. For studying the relative expression of immuno-stimulatory genes (IFN-α, IFN-β, IFN-γ, IL-1β, iNOS and OAS) in CAM, TLR ligands were administered through intra-allantoicroute and CAM were collected at 4, 8 and 16 h post treatment. The results demonstrated that intermediate dose of all the three TLR ligands significantly reduced virus titers and used in the present study. However, the LPS reduced virus titer pre- and post-IBV infection but Pam3CSK4 and CpG ODN reduced only pre-IBV infection. Further analysis showed that TLR ligands induced IFN-γ, IL-1β and IFN stimulated genes viz. iNOS and OAS genes in CAM. The present study pointed towards the novel opportunities for rational design of LPS as immuno-stimulatory agent in chickens with reference to IBV. It may be speculated that in ovo administration of these TLR ligands may enhance resistance against viral infection in neonatal chicken and may contribute towards the development of more effective and safer vaccines including in ovo vaccines.


title: Intracerebral delivery of small interfering RNAs (siRNAs) using adenoviral vector protects mice against lethal peripheral rabies challenge

text: Abstract To investigate the potential of RNA interference (RNAi) as antiviral agent against rabies, two small interfering RNAs (siRNAs) targeting rabies virus (RABV) nucleoprotein (N) and polymerase (L) genes were designed and evaluated. Both siRNAs knockdown or silenced the target RABV genes as evaluated in a plasmid based transient expression model. For efficient delivery, adenoviruses expressing the siRNAs were constructed and antiviral potential of the delivered siRNAs was investigated in BHK-21 cells. When cells treated with adenoviruses expressing siRNAs were challenged with RABV, there was 88.35±2.4% and 41.52±9.3% reduction in RABV multiplication in infected cells with siRNAs targeting RABV-N and L genes, respectively. Relative quantification of RABV transcripts using real-time PCR revealed knockdown of both RABV-N and L gene transcripts, however, significant reduction was observed only with adenovirus expressing siRNA against RABV-N. When mice treated intracerebrally with adenoviruses expressing siRNAs were challenged peripherally with lethal RABV by the intramuscular route in masseter muscle, there was 66.6% and 33.3% protection with adenoviruses expressing siRNAs against RABV-N and L genes, respectively. These results demonstrated that adenovirus expressing siRNA against RABV-N efficiently inhibited the RABV multiplication both, in vitro and in vivo and conferred significant protection against lethal RABV challenge. This supported the hypothesis that RNAi, based on siRNA targeting RABV-N gene can prevent RABV infection and holds the potential of RNAi as an approach to prevent rabies infection.


title: RNA granules: the good, the bad and the ugly

text: Processing bodies (PBs) and Stress granules (SGs) are the founding members of a new class of RNA granules, known as mRNA silencing foci, as they harbor transcripts circumstantially excluded from the translationally active pool. PBs and SGs are able to release mRNAs thus allowing their translation. PBs are constitutive, but respond to stimuli that affect mRNA translation and decay, whereas SGs are specifically induced upon cellular stress, which triggers a global translational silencing by several pathways, including phosphorylation of the key translation initiation factor elF2alpha, and tRNA cleavage among others. PBs and SGs with different composition may coexist in a single cell. These macromolecular aggregates are highly conserved through evolution, from unicellular organisms to vertebrate neurons. Their dynamics is regulated by several signaling pathways, and depends on microfilaments and microtubules, and the cognate molecular motors myosin, dynein, and kinesin. SGs share features with aggresomes and related aggregates of unfolded proteins frequently present in neurodegenerative diseases, and may play a role in the pathology. Virus infections may induce or impair SG formation. Besides being important for mRNA regulation upon stress, SGs modulate the signaling balancing apoptosis and cell survival. Finally, the formation of nuclear stress bodies (nSBs), which share components with SGs, and the assembly of additional cytosolic aggregates containing RNA—the UV granules and the Ire1 foci—, all them induced by specific cell damage factors, contribute to cell survival.


title: Pathogenesis and Diagnostic Approaches of Avian Infectious Bronchitis

text: Infectious bronchitis (IB) is one of the major economically important poultry diseases distributed worldwide. It is caused by infectious bronchitis virus (IBV) and affects both galliform and nongalliform birds. Its economic impact includes decreased egg production and poor egg quality in layers, stunted growth, poor carcass weight, and mortality in broiler chickens. Although primarily affecting the respiratory tract, IBV demonstrates a wide range of tissues tropism, including the renal and reproductive systems. Thus, disease outcome may be influenced by the organ or tissue involved as well as pathotypes or strain of the infecting virus. Knowledge on the epidemiology of the prevalent IBV strains in a particular region is therefore important to guide control and preventions. Meanwhile previous diagnostic methods such as serology and virus isolations are less sensitive and time consuming, respectively; current methods, such as reverse transcription polymerase chain reaction (RT-PCR), Restriction Fragment Length Polymorphism (RFLP), and sequencing, offer highly sensitive, rapid, and accurate diagnostic results, thus enabling the genotyping of new viral strains within the shortest possible time. This review discusses aspects on pathogenesis and diagnostic methods for IBV infection.


title: Epidemiological characteristics of pulmonary tuberculosis in Shandong, China, 2005–2017: A retrospective study

text: This study aimed to analyze the epidemiology of pulmonary tuberculosis (PTB) and gained insight into the future TB control plan in China. We extracted epidemiological, clinical, and geographic data from TB prevention and control institutions in 6 cities of Shandong province, China, during 2005 to 2017. Among 224,480 diagnosed PTB, rural residents accounted for 93%, smear-positive PTB 52%, and new cases 92%. The incidence rate of overall PTB declined from 40.8 to 26.25 per 100,000 during 2005 to 2017. Except smear-negative PTB (7.57–19.87 per 100,000), the incidence of smear-positive PTB and all that stratified by age, sex, and treatment history decreased. With 80% reduction, the incidence of smear-positive PTB (6.38 per 100,000) and relapse cases (1.01 per 100,000) were already very low in 2017. With persistent efforts to combat TB, the disease burden had shifted from smear-positive PTB to smear-negative PTB. While new cases need continuous attention, further reducing the incidence of smear-negative PTB and elderly patients may have a greater impact on future TB control.


title: How Might AI and Chest Imaging Help Unravel COVID-19’s Mysteries?

text: Artificial intelligence (AI) has the potential to expand the role of chest imaging in COVID-19 beyond diagnosis to enable risk stratification, treatment monitoring, and discovery of novel therapeutic targets. AI’s power to generate models from large volumes of information – fusing molecular, clinical, epidemiological, and imaging data – may accelerate solutions to detect, contain, and treat COVID-19.


Italian Radiology's response to the COVID-19 outbreak


title: Construction and genetic analysis of murine hepatitis virus strain A59 Nsp16 temperature sensitive mutant and the revertant virus

text: Coronaviruses (CoVs) are generally associated with respiratory and enteric infections and have long been recognized as important pathogens of livestock and companion animals. Mouse hepatitis virus (MHV) is a widely studied model system for Coronavirus replication and pathogenesis. In this study, we created a MHV-A59 temperature sensitive (ts) mutant Wu”-ts18(cd) using the recombinant vaccinia reverse genetics system. Virus replication assay in 17C1-1 cells showed the plaque phenotype and replication characterization of constructed Wu”-ts18(cd) were indistinguishable from the reported ts mutant Wu”-ts18. Then we cultured the ts mutant Wu”-ts18(cd) at non-permissive temperature 39.5°C, which “forced” the ts recombinant virus to use second-site mutation to revert from a ts to a non-ts phenotype. Sequence analysis showed most of the revertants had the same single amino acid mutation at Nsp16 position 43. The single amino acid mutation at Nsp16 position 76 or position 130 could also revert the ts mutant Wu”-ts18 (cd) to non-ts phenotype, an additional independent mutation in Nsp13 position 115 played an important role on plaque size. The results provided us with genetic information on the functional determinants of Nsp16. This allowed us to build up a more reasonable model of CoVs replication-transcription complex.


title: New technology and clinical applications of nanomedicine: Highlights of the second annual meeting of the American Academy of Nanomedicine (Part I)

text: Abstract The Second Annual Meeting of the American Academy of Nanomedicine (AANM) was held at the National Acadmy of Science Building in Washinton, DC, September 9–10, 2006. The program included two Nobel Prize Laureate Lectures, two Keynote Lectures, and 123 invited outstanding State-in-Art lectures presenting in 23 special concurrent symposia. In addition, there were 22 poster presentations in the meeting addressing different areas in nanomedicine research. All of the presenters at the meeting are outstanding investigators and researchers in the field. The Second Annual Meeting of the AANM was a great success. The meeting provides investigators from different world areas a forum and an opportunity for discussion. We believe that nanomedicine research will develop rapidly in the future. The AANM invites basic and clinical researchers from the world to join this exciting research.


title: Een groene herstart van patiënt aardbol?

text: Klimaatverandering is de grootste bedreiging voor de volksgezondheid op aarde in de 21(e) eeuw. Zo luidt de conclusie van een internationale groep wetenschappers die onderzoek heeft gedaan naar de effecten van de klimaatverandering op de gezondheid van de wereldbevolking. Er zijn steeds meer voorbeelden dat klimaatverandering en gezondheid niet los van elkaar staan.


title: A minor groove binder probe real-time PCR assay for discrimination between type 2-based vaccines and field strains of canine parvovirus

text: A minor groove binder (MGB) probe assay was developed to discriminate between type 2-based vaccines and field strains of canine parvovirus (CPV). Considering that most of the CPV vaccines contain the old type 2, no longer circulating in canine population, two MGB probes specific for CPV-2 and the antigenic variants (types 2a, 2b and 2c), respectively, were labeled with different fluorophores. The MGB probe assay was able to discriminate correctly between the old type and the variants, with a detection limit of 10(1) DNA copies and a good reproducibility. Quantitation of the viral DNA loads was accurate, as demonstrated by comparing the CPV DNA titres to those calculated by means of the TaqMan assay recognising all CPV types. This assay will ensure resolution of most diagnostic problems in dogs showing CPV disease shortly after CPV vaccination, although it does not discriminate between field strains and type 2b-based vaccines, recently licensed to market in some countries.


title: Importance of Viral Disease in Dairy Cow Fertility

text: Abstract Many viral diseases are endemic in cattle populations worldwide. The ability of many viruses to cross the placenta and cause abortions and fetal malformations is well understood. There is also significant evidence that viral infections have additional actions in dairy cows, which are reflected in reduced conception rates. These effects are, however, highly dependent on the time at which an individual animal first contracts the disease and are less easy to quantify. This paper reviews the evidence relating to five viruses that can affect fertility, together with their potential mechanisms of action. Acute infection with non-cytopathic bovine viral diarrhea virus (BVDV) in mid-gestation increases abortion rates or causes the birth of persistently infected calves. BVDV infections closer to the time of breeding can have direct effects on the ovaries and uterine endometrium, which cause estrous cycle irregularities and early embryo mortality. Fertility may also be reduced by BVDV-induced immunosuppression, which increases the susceptibility to bacterial infections. Bovine herpesvirus (BHV)-1 is most common in pre-pubertal heifers, and can slow their growth, delay breeding, and increase the age at first calving. Previously infected animals subsequently show reduced fertility. Although this may be associated with lung damage, ovarian lesions have also been reported. Both BHV-1 and BHV-4 remain latent in the host following initial infection and may be reactivated later by stress, for example associated with calving and early lactation. While BHV-4 infection alone may not reduce fertility, it appears to act as a co-factor with established bacterial pathogens such as Escherichia coli and Trueperella pyogenes to promote the development of endometritis and delay uterine repair mechanisms after calving. Both Schmallenberg virus (SBV) and bluetongue virus (BTV) are transmitted by insect vectors and lead to increased abortion rates and congenital malformations. BTV-8 also impairs the development of hatched blastocysts; furthermore, infection around the time of breeding with either virus appears to reduce conception rates. Although the reductions in conception rates are often difficult to quantify, they are nevertheless sufficient to cause economic losses, which help to justify the benefits of vaccination and eradication schemes.


title: The α(1,2)-mannosidase I inhibitor 1-deoxymannojirimycin potentiates the antiviral activity of carbohydrate-binding agents against wild-type and mutant HIV-1 strains containing glycan deletions in gp120

text: Abstract Exposure of carbohydrate-binding agents (CBAs) (i.e. the mannose-specific plant lectins Hippeastrum hybrid agglutinin and Galanthus nivalis agglutinin) to HIV-1 progressively select for mutant HIV-1 strains that contain N-glycan deletions in their envelope gp120. This results in resistance of the mutant virus strains to the CBAs. Exposure of such mutant virus strains to the α(1,2)-mannosidase I inhibitor 1-deoxymannojirimycin (DMJ) results in an enhanced suppression of mutant virus-induced cytopathicity in CEM cell cultures. Moreover, when combined with CBAs at concentrations that showed poor if any suppression of mutant virus replication as single drugs, a synergistic antiviral activity of DMJ was observed. These observations argue for a combined exposure of CBAs and glycosylation inhibitors such as DMJ to HIV to afford a more pronounced suppression of virus replication, prior to, or during, CBA resistance development.


title: Formation and activity of covalent conjugates of poliovirus and ligands binding to cell surface structures

text: Abstract Disulfide-linked conjugates of poliovirus with streptavidin or concanavalin A were formed and the binding of the conjugates to mouse L cells that lack natural poliovirus receptors was studied. The conjugate with streptavidin was specifically bound to biotinylated L cells, but not to unmodified L cells. The conjugate with conA was bound to L cells in the absence of, but not in the presence of α-methyl mannoside. Incubation of L cells with bound conjugates did not produce virus, although the conjugates were highly infectious in HeLa cells, containing natural poliovirus receptors. This suggests that the artificially bound virus was unable to penetrate the L cells and start replication. The possibility that binding of the virus to the natural receptor is required for efficient infection is discussed.


title: Early experience with convalescent plasma as immunotherapy for COVID‐19 in China: Knowns and unknowns

text: BACKGROUND AND OBJECTIVES: In the absence of a vaccine or specific drug treatment options for coronavirus disease (COVID‐19), attention has been shifted in China to the possible therapeutic use of convalescent plasma. COVID‐19 convalescent plasma (CCP) is currently under investigation. We summarized clinical studies and other research data available as of May 5, 2020, on CCP therapy according to the Clinical Treatment Guideline of COVID‐19 Convalescent Plasma in China, as well as clinical experience at the First Affiliated Hospital of Zhejiang University, as part of a comprehensive anti‐epidemic strategy. MATERIALS AND METHODS: As of May 5, 2020, when the epidemic was well‐controlled in China, healthcare databases and sources of English literature relating to convalescent plasma were searched and reviewed. Sources of clinical and methodological heterogeneity were identified. RESULTS: As of May 5, 2020, up to 2,000 samples of CCP had been collected across China and administered to 700 COVID‐19 patients. From donors, 200–400 mL of plasma were collected at each donation, with antibody titers >1:160. We identified three clinical studies for COVID‐19 in China. Analyses showed a statistically significant improvement in clinical outcomes compared with untreated cases (P<0.001). No adverse effects were reported. CONCLUSION: From initial studies, convalescent plasma therapy appears effective and safe for COVID‐19. However, there is clearly a need for well‐designed RCTs (randomized controlled trials) or other formal studies to further evaluate the efficacy and any potential adverse effects of CCP.


title: Lobar Distribution of COVID-19 Pneumonia Based on Chest Computed Tomography Findings; A Retrospective Study

text: INTRODUCTION: Computed tomography (CT) imaging has quickly found its place as a beneficial tool in the detection of coronavirus disease 2019 (COVID-19). To date, only a few studies have reported the distribution of lung lesions by segment. This study aimed to evaluate the lobar and segmental distribution of COVID-19 pneumonia based on patients’ chest CT scan. METHODS: This was a retrospective study performed on 63 Iranian adult patients with a final diagnosis of COVID-19. All patients had undergone chest CT scan on admission. Demographic data and imaging profile, including segmental distribution, were evaluated. Moreover, a scoring scale was designed to assess the severity of ground-glass opacification (GGO). The relationship of GGO score with age, sex, and symptoms at presentation was investigated. RESULTS: Among included patients, mean age of patients was 54.2 ±14.9 (range: 26 - 81) years old and 60.3% were male. Overall, the right lower lobe (87.3%) and the left lower lobe (85.7%) were more frequently involved. Specifically, predominant involvement was seen in the posterior segment of the left lower lobe (82.5%). The most common findings were peripheral GGO and consolidation, which were observed in 92.1% and 42.9% of patients, respectively. According to the self-designed GGO scoring scale, about half of the patients presented with mild GGO on admission. GGO score was found to be equally distributed among different sex and age categories; however, the presence of dyspnea on admission was significantly associated with a higher GGO score (p= 0.022). Cavitation, reticulation, calcification, bronchiectasis, tree-in-bud appearance and nodules were not identified in any of the cases. CONCLUSION: COVID-19 mainly affects the lower lobes of the lungs. GGO and consolidation in the lung periphery is the imaging hallmark in patients with COVID-19 infection. Absence of bronchiectasis, solitary nodules, cavitation, calcifications, tree-in-bud appearance, and reversed halo-sign indicates that these features are not common findings, at least in the earlier stages.