title: Probing the structure of the SARS coronavirus using scanning electron microscopy.

text: A novel coronavirus, SARS-CoV, has been confirmed to be the aetiological agent of SARS. Transmission electron microscope (TEM) images played an important role in initial identification of the pathogen. In order to obtain greater morphological detail of SARS-CoV than could be obtained by TEM, we used ultra-high resolution scanning electron microscopy (SEM) to image the virus particles. We show here the three-dimensional appearance of SARS-CoV. Enhanced detail of the ultrastructure reveals the trimeric structure of the 10-20 nm spikes on the virion surface. These results contribute to characterization of the SARS agent and development of new antiviral strategies.


title: Severe Acute Respiratory Syndrome (SARS): loud clang of the Leper's bell.

text: Severe acute respiratory syndrome (SARS) or the "Chinese Chernobyl" emerged against an alarming background of rising infectious disease in poor rural China and to a backdrop of interregional and global polarization of population well-being and vulnerability. SARS has added its own dissonant note to "health disturbance", caused fear and panic and disrupted international commerce. Its emergence should be perceived as a disturbing alarm that underscores the need to strengthen public health and facilitate construction of a human security "umbrella" in the event of future disasters. Although SARS has produced a relatively insignificant level of damage when compared to other threats, its long-term effects on health should not be underestimated, based on its unexpected appearance and still unknown properties. This essay presents a qualitative flowchart that follows SARS from its origin in China to the accumulation of global damage. Two future scenarios were formulated, covering a worse-case outcome and containment outcome, which currently appears to be the case. In the event of the worst-case scenario it is doubtful whether any health service in Europe could cope. In either case, the development of a European Union Center for Disease Control is mandatory.


title: Typing of field isolates of infectious bronchitis virus based on the sequence of the hypervariable region in the S1 gene.

text: A universal primer set was developed that amplifies a region covering hypervariable region (HVR) 1 and HVR 2 in the S1 gene of the infectious bronchitis virus (IBV). The universality of this primer set was confirmed by testing the reference strains of different serotypes or variants of the IBV present in the United States. An approximately 450-bp region containing HVR 1 and HVR 2 of 7 untyped field isolates obtained in 1999 and 2000 was amplified. Direct sequencing followed by phylogenetic analysis on that region allowed us to type those field isolates that were not typable by reverse transcriptase-polymerase chain reaction (RT-PCR) and restriction fragment length polymorphism (RFLP). Furthermore, it was found that typing by phylogenetic analysis of that region correlates with virus neutralization results. Together with RT-PCR and RFLP, this method will serve as a fast typing method for IBV diagnosis.


title: Transient disorder in dynamically growing networks.

text: When a certain "seed" disturbance begins to spread on a large network, the number of nodes infected is a function of time. Regarding the set of infected nodes as constituting a dynamic network that evolves continuously in time, we ask: how does the order in the collective dynamics of the network vary with time? Utilizing synchronizability as a measure of the order, we find that there exists a time at which a maximum amount of disorder corresponding to a minimum degree of synchronizability can arise before the system settles into a more ordered steady state. This phenomenon of transient disorder occurs for networks of both regular and complex topologies. We present physical analyses and numerical support to establish the generality of the phenomenon.


title: Viral infections in free-living populations of the European wildcat.

text: While the importance of viral infections is well studied in domestic cats, only limited information is available on their occurence and prevalence in the European wildcat (Felis silvestris silvestris). The aim of this study was to determine the prevalence of antibodies to feline coronavirus (FCoV), calicivirus (FCV), herpesvirus (FHV), parvovirus (FPV), immunodeficiency virus (FIV), leukemia virus (FeLV), and FeLV antigenemia in 51 European wildcat sera. Samples were collected between 1996 and 1997 from wildcat populations in France, Switzerland, and Germany. Antibodies to FCoV were detected in two cats (4%) and FCoV RNA was detected in feces of one of these two cats. Antibodies to FCV, FHV and FPV were found at relatively low frequencies of 16%, 4%, and 2%, respectively. Antibodies to FIV were not detected. Although antigen and antibodies to FeLV were detected in 49%, and 75%, respectively, no evidence of FeLV-associated pathology was found. From the low prevalence of FCoV, FCV, FHV and FPV infections and from the fact that the European wildcats live solitarily, it was concluded that these viral infections do not spread readily within a population. Therefore, it may be assumed that release into the wild of European wildcats bred in captivity would not bring about a high risk of introducing of these viral infections to the free-ranging wildcats. As an exception, wildcats should be tested for absence of FIV infection before release if they were at risk to acquire this infection from domestic cats.


title: A system for study of coronavirus mRNA synthesis: a regulated, expressed subgenomic defective interfering RNA results from intergenic site insertion.

text: A system that exploits defective interfering (DI) RNAs of mouse hepatitis virus (MHV) for deciphering the mechanisms of coronavirus mRNA transcription was developed. A complete cDNA clone of MHV DI RNA containing an inserted intergenic region, derived from the area of genomic RNA between genes 6 and 7, was constructed. After transfection of the in vitro-synthesized DI RNA into MHV-infected cells, replication of genomic DI RNA as well as transcription of the subgenomic DI RNA was observed. S1 nuclease protection experiments, sequence analysis, and Northern (RNA) blotting analysis revealed that the subgenomic DI RNA contained the leader sequence at its 5' end and that the body of the subgenomic DI RNA started from the inserted intergenic sequence. Two subgenomic DI RNAs were synthesized after inserting two intergenic sites into the MHV DI RNA. Metabolic labeling of virus-specific protein in DI RNA replicating cells demonstrated that a protein was translated from the subgenomic DI RNA, which can therefore be considered a functional mRNA. Transfection study of gel-purified genomic DI RNA and subgenomic DI RNA revealed that the introduction of the genomic DI RNA, but not subgenomic DI RNA, into MHV-infected cells was required for synthesis of the subgenomic DI RNA. A series of deletion mutations in the intergenic site demonstrated that the sequence flanking the consensus sequence of UCUAAAC affected the efficiency of subgenomic DI RNA transcription and that the consensus sequence was necessary but not sufficient for the synthesis of the subgenomic DI RNA.


title: Coronavirus spike glycoprotein, extended at the carboxy terminus with green fluorescent protein, is assembly competent.

text: Due to the limited ultrastructural information about the coronavirion, little is known about the interactions acting at the interface between nucleocapsid and viral envelope. Knowing that subtle mutations in the carboxy-terminal endodomain of the M protein are already lethal, we have now probed the equivalent domain of the spike (S) protein by extending it terminally with a foreign sequence of 27 kDa: the green fluorescent protein (GFP). When expressed individually in murine cells, the S-GFP chimeric protein induced the formation of fluorescent syncytia, indicating that it was synthesized and folded properly, trimerized, and transported to the plasma membrane, where it exhibited the two key S protein functions, i.e., interaction with virus receptor molecules and membrane fusion. Incorporation into virus-like particles demonstrated the assembly competence of the chimeric spike protein. The wild-type S gene of mouse hepatitis coronavirus (MHV) was subsequently replaced by the chimeric construct through targeted recombination. A viable MHV-SGFP was obtained, infection by which could be visualized by the fluorescence induced. The efficiency of incorporation of the chimeric protein into particles was, however, reduced relative to that in wild-type particles which may explain, at least in part, the reduced infectivity produced by MHV-SGFP infection. We conclude that the incorporation of spikes carrying the large GFP moiety is apparently impaired by geometrical constraints and selected against during the assembly of virions. Probably due to this disadvantage, deletion mutants, having lost the foreign sequences, rapidly evolved and outcompeted the chimeric viruses during virus propagation. The fluorescent MHV-SGFP will now be a convenient tool to study coronaviral cell entry.


title: Canine Circovirus 1 (CaCV-1) and Canine Parvovirus 2 (CPV-2): Recurrent Dual Infections in a Papillon Breeding Colony.

text: Recurrent outbreaks of sudden death and bloody diarrhea were reported in March 2013 and February 2014 in a breeding colony of Papillon dogs. During the first outbreak, 1 adult dog and 2 eight-month-old puppies died. During the second outbreak, 2 ten-week-old puppies died. One puppy from the first outbreak and 2 puppies from the second outbreak were examined at necropsy. Histologically, all 3 puppies had severe segmental crypt necrosis of the small intestine and marked lymphoid follicle depletion in the spleen and Peyer's patches. Real-time (RT) polymerase chain reaction (PCR) demonstrated abundant canine parvovirus (CPV-2) DNA (Ct<15) in the affected small intestine, and immunohistochemistry detected large amounts of CPV-2 antigen in intestinal crypt epithelium and Kupffer cells but few positive macrophages in lymphoid organs. All puppies had marked sinusoidal histiocytosis and multifocal granulomatous inflammation in mesenteric lymph nodes and spleen, prompting additional RT-PCR testing for canine circovirus 1 (CaCV-1). Very high levels of CaCV-1 DNA (Ct<13) were detected in small intestine, lymph nodes, and spleen. In situ hybridization for CaCV-1 detected rare positive nuclei of regenerating crypt epithelium but abundant amounts of CaCV-1 nucleic acid in the cytoplasm and nuclei of histiocytes in all lymphoid tissues, including granulomatous inflammatory foci and hepatic Kupffer cells. Significant levels of CaCV-1 DNA were detected in blood and serum (Ct as low as 13) but not feces from 3 surviving dogs at 2 months or 1 year after the outbreak, respectively. We hypothesize that CPV-2 infection predisposed dogs to CaCV-1 infection and ultimately resulted in more severe clinical disease.


title: The coronaviruses.

text: Coronaviruses of human origin have emerged as probable important etiologic agents of acute upper respiratory tract illnesses in adults; their role in the etiology of respiratory illnesses of childhood is less certain. The first coronavirus of human origin, B814, was described in 1965 and since that time only 31 additional strains have been recovered. Ten of these were originally recovered in human embryonic tracheal organ culturesonly, and the remainder in monolayer cell cultures. All of the latter group were antigenically related to a prototype strain designated 229e. As a result of the fastidious growth requirements of these agents, most of the knowledge concerning the clinical syndromes associated with them has come from chajlenge studies in volunteers and seroepidemiologic investigations. Coronaviruses have been shown to be associated with a substantial number of adult respiratory illnesses especially during certain periods when rhinovirus infections are infrequent. Progress in propagating coronaviruses and in detecting coronavirus infections has been achieved recently: viruses similar to 229E were successfully recovered in human embryonic intestine cell cultures from patients with upper respiratory tract illnesses; 30C strains (B814, LP and EVS) were recovered in L132 cell cultures from infectious nasal washings; OC43(and OC38) viruses which were originally recovered in OC and later adapted to grow in suckling mice were not only shown to directly hemagglutinate various erythrocytes but were also adapted to grow in MK cell cultures; OC43 virus was also found to induce hemadsorption of rat and mouse erythrocytes in certain cell cultures; and a coronavirus strain was detected by immune electron microscopy. Coronaviruses are also associated with certain diseases in animals.


title: Comprehensive characterization of MHC class II haplotypes in Mauritian cynomolgus macaques.

text: There are currently no nonhuman primate models with fully defined major histocompatibility complex (MHC) class II genetics. We recently showed that six common MHC haplotypes account for essentially all MHC diversity in cynomolgus macaques (Macaca fascicularis) from the island of Mauritius. In this study, we employ complementary DNA cloning and sequencing to comprehensively characterize full length MHC class II alleles expressed at the Mafa-DPA, -DPB, -DQA, -DQB, -DRA, and -DRB loci on the six common haplotypes. We describe 34 full-length MHC class II alleles, 12 of which are completely novel. Polymorphism was evident at all six loci including DPA, a locus thought to be monomorphic in rhesus macaques. Similar to other Old World monkeys, Mauritian cynomolgus macaques (MCM) share MHC class II allelic lineages with humans at the DQ and DR loci, but not at the DP loci. Additionally, we identified extensive sharing of MHC class II alleles between MCM and other nonhuman primates. The characterization of these full-length-expressed MHC class II alleles will enable researchers to generate MHC class II transferent cell lines, tetramers, and other molecular reagents that can be used to explore CD4+ T lymphocyte responses in MCM.


Surgical Procedures and Short-Term Outcomes of a Complete Laparoscopic Colectomy with Intracorporeal Anastomosis for Right-Sided Colon Cancer.


title: Factors associated with the psychological impact of severe acute respiratory syndrome on nurses and other hospital workers in Toronto.

text: OBJECTIVES A survey was conducted to measure psychological stress in hospital workers and measure factors that may have mediated acute traumatic responses. METHODS A self-report survey was completed by 1557 healthcare workers at three Toronto hospitals in May and June 2003. Psychological stress was measured with the Impact of Event Scale. Scales representing attitudes to the outbreak were derived by factor analysis of 76 items probing attitudes to severe acute respiratory syndrome. The association of Impact of Event Scale scores to job role and contact with severe acute respiratory syndrome patients was tested by analysis of variance. Between-group differences in attitudinal scales were tested by multivariate analysis of variance. Attitudinal scales were tested as factors mediating the association of severe acute respiratory syndrome patient contact and job role with total Impact of Event Scale by linear regression. RESULTS Higher Impact of Event Scale scores are found in nurses and healthcare workers having contact with patients with severe acute respiratory syndrome. The relationship of these groups to the Impact of Event Scale score is mediated by three factors: health fear, social isolation, and job stress. CONCLUSIONS Although distress in response to the severe acute respiratory syndrome outbreak is greater in nurses and those who care for patients with severe acute respiratory syndrome, these relationships are explained by mediating variables that may be available for interventions to reduce stress in future outbreaks. In particular, the data suggest that the targets of intervention should include job stress, social isolation, and health fear.


title: Clinical prognostic rules for severe acute respiratory syndrome in low- and high-resource settings.

text: BACKGROUND An accurate prognostic model for patients with severe acute respiratory syndrome (SARS) could provide a practical clinical decision aid. We developed and validated prognostic rules for both high- and low-resource settings based on data available at the time of admission. METHODS We analyzed data on all 1755 and 291 patients with SARS in Hong Kong (derivation cohort) and Toronto (validation cohort), respectively, using a multivariable logistic scoring method with internal and external validation. Scores were assigned on the basis of patient history in a basic model, and a full model additionally incorporated radiological and laboratory results. The main outcome measure was death. RESULTS Predictors for mortality in the basic model included older age, male sex, and the presence of comorbid conditions. Additional predictors in the full model included haziness or infiltrates on chest radiography, less than 95% oxygen saturation on room air, high lactate dehydrogenase level, and high neutrophil and low platelet counts. The basic model had an area under the receiver operating characteristic (ROC) curve of 0.860 in the derivation cohort, which was maintained on external validation with an area under the ROC curve of 0.882. The full model improved discrimination with areas under the ROC curve of 0.877 and 0.892 in the derivation and validation cohorts, respectively. CONCLUSION The model performs well and could be useful in assessing prognosis for patients who are infected with re-emergent SARS.


title: The use of Permacol™ mesh in contaminated complex abdominal wall defects.

text: The repair of complex abdominal wall defects in contaminated fields often presents a dilemma for general surgeons. Synthetic mesh, although strong, may lead to chronic infection or even visceral erosion. Leaving the abdomen open presents challenges for ward management and delays definitive care, as well as allowing the musculature to retract over time. Numerous biological mesh alternatives have arisen over the previous decade, which may make primary closure in this setting a practical alternative, although durability may prove the downside. Here we present our local experience with PermacolTM mesh (Porcine Acellular Dermal Matrix - PADM; Covidien, Mansfield, MA) in four challenging cases and discuss the role this relatively new mesh may have for these and other applications.


title: A retrospective clinical review of extracellular matrices for tissue reconstruction: equine pericardium as a biological covering to assist with wound closure .

text: Complex wounds frequently undergo surgical excision and grafting in an attempt to optimize the wound environment and to facilitate wound closure. Individuals who have not responded to conventional non-surgical therapies and dressings may not be good candidates for autologous grafting. A fully flexible, cross-linked, acellular equine pericardium biological xenograft was used to address difficult-to-treat and recalcitrant wounds of the lower extremity. Twenty-four complex wounds of varying etiology, including diabetic, venous, trauma, vasculitic, and post-surgical wounds underwent surgical debridement and xenograft application. The individual results were reviewed in a retrospective study over an 18-month period. The duration of the wounds ranged between 3 months to 2 years. The average time to wound closure was 5.96 weeks. The median time to closure was 6 weeks. No significant adverse events were noted. The data review suggests the use of equine pericardium as a xenograft and biological cover may significantly benefit patients with difficult-to-heal wounds. Additional animal and clinical studies are in progress to help understand the mechanism of action of the xenograft in the clinical environment.


title: Endovascular management of giant middle cerebral artery aneurysms.

text: BACKGROUND This article reported the experience of endovascular treatment in giant middle cerebral artery (MCA) aneurysms with parent artery occlusion or stent-assisted coiling. MATERIAL AND METHODS Eleven consecutive patients with giant MCA aneurysms were included. The aneurysms predominantly involved the M1 segment in two cases, bifurcation in four cases, and M2 in five cases. Four M2 fusiform aneurysms were treated with parent artery sacrifice after balloon occlusion test. The seven unruptured aneurysms and one ruptured one were treated with stent-assisted coiling. The post-operation and long-term follow-up angiographic and clinical outcomes were analyzed. RESULTS Endovascular coiling was performed successfully in all 11 cases. All four M2 fusiform cases using parent artery occlusion strategy achieved complete occlusion of aneurysms. In the seven cases with stent-assisted coiling, four were completely occluded, two were partially occluded and one remained small residue. Mild perioperative complications occurred in six patients. The follow-up angiography taken at a mean of 13.5 months of eight patients showed that seven aneurysms remained stable or improved and one M1 aneurysms relapsed and needed further treatment. CONCLUSION Stent-assisted coiling or parent artery occlusion of selected giant MCA aneurysms is an option to consider.


SARS and occupational health in the air.


title: [Epidemiological perspectives on SARS and avian influenza].

text: SARS is a respiratory infection caused by Coronavirus (Nidoviruses, RNA) from which 3 groups are known. Group 1 affects dogs, cats, pigs, and the human agent is 229 E. Group 2 affects bovines or rodents, and the human agent is OC43. And group 3 corresponds to the avian pathology.... The epidemics emerged on February 2003 in Guangdong, South China, due to consumption of exotic animals (Civeta, etc.), and it spread through interperson contagion to other regions in Asia, America and Europe. Incubation period is about 2-7 days. Transmission Of the virus is person-to person, but also by excretions and residual water. Basic reproductive rate is 2 to 4, and it is considered that 2.7 persons are infected from the initial case. In June 2003, SARS affected over 8,000 people and 774 were killed. Mortality approaches to 10%, and it is higher among older people rising up to 50% in those aged over 65 years. It is important to quickly establish action protocols regarding clinical, epidemiological and prevention aspects. Avian influenza is an infection caused by type A Influenza Orthomixovirus, in which migration birds and wild ducks are the main reservoir. Avian viruses correspond to H5, H7, H9. In 1997 it was observed that type AH5N1 jumped interspecies barrier and affected 18 humans, and 6 of them died. At the end of 2003 and in 2004 this type of poultry flu was described in Asia. FAO has emphasized that sacrifice of chicken in affected farms is the most effective measure to fight against the disease. It has also been established suppression of imports from these countries. There is no evidence on interperson contagion from chicken contagion, nor on food-borne contagion to humans.


title: The effects of processing inhibitors of N-linked oligosaccharides on the intracellular migration of glycoprotein E2 of mouse hepatitis virus and the maturation of coronavirus particles.

text: We have studied the effects of tunicamycin and inhibitors of the processing of N-linked glycans including N-methyl-1-deoxynojirimycin, castanospermine, mannodeoxynojirimycin, and swainsonine on the transport of glycoprotein E2 and the intracellular maturation of the coronavirus mouse hepatitis virus A59. Indirect immunofluorescence staining with monoclonal antibodies revealed that glycoprotein E2 exhibits different antigenic properties depending on the presence and on the structure of the N-linked oligosaccharides and that efficient transport of glycoprotein E2 to the plasma membrane requires the removal of glucose residues. In the presence of tunicamycin in the nonglycosylated E2 apoprotein was synthesized in normal amounts and readily acylated throughout the infectious cycle. This E2-species could not be detected on the surface of mouse hepatitis virus A59-infected cells with indirect immunofluorescence staining or lactoperoxidase labeling. N-Methyl-1-deoxynojirimycin and castanospermine, both of which selectively inhibited the processing glucosidases, caused a drop in virion formation by two log steps and a drastic delay in the surface expression of glycoprotein E2. The E2 species synthesized under such conditions was acylated but accumulated intracellularly in a compartment distinct from the Golgi. Concomitantly, synthesis of the matrix glycoprotein E1 of mouse hepatitis virus A59 was drastically impaired. Mannodeoxynojirimycin and swainsonine, which block later stages of the processing pathway, had less or no effect on the transport of glycoprotein E2 and the formation of virus particles.


Physician mobility in Canada.


title: Analysis on the co-localization of asbestos bodies and Fas or CD163 expression in asbestos lung tissue by in-air micro-pixe.

text: To prevent and control disease caused by exposure to various agents, it is necessary to determine the harmful level of intervention and to establish a method for measuring that level. In-air microparticle-induced X-ray emission (in-air micro-PIXE) analysis is based on irradiation of specimens with a proton ion microbeam, and has been modified for biological application. Two-dimensional analysis and quantitative analysis using the system confirmed that asbestos induced apoptosis by upregulating Fas expression and also revealed the accumulation of CD163-expressing macrophages in the lungs of patients with asbestosis. By quantitative comparison of the area of Fas or CD163 expression and the Fas- or CD163-negative area in asbestos lung tissue, the harmful levels which caused the expression of Fas or CD163 could be estimated on Silica, Ferrous iron, and Magnesium (the components of asbestos) deposition. These results indicate that the system could be useful for investigating the pathogenesis of inhaled particle-induced immune reactions and for determining harmful levels of exogenous agents.


title: Interactions between the cytoplasmic proteins and the intergenic (promoter) sequence of mouse hepatitis virus RNA: correlation with the amounts of subgenomic mRNA transcribed.

text: Previous studies suggested that coronavirus RNA transcription involves interaction between leader RNA and the intergenic (IG) sequences, probably via protein-RNA interactions (X. M. Zhang, C.-L. Liao, and M. M. C. Lai, J. Virol., 68:4738-4746, 1994; X. M. Zhang and M. M. C. Lai, J. Virol., 68:6626-6633, 1994). To determine whether cellular proteins are involved in this process, we performed UV cross-linking experiments using cytoplasmic extracts of uninfected cells and the IG (promoter) sequence between genes 6 and 7 (IG7) and the 5' untranslational region of mouse hepatitis virus genomic RNA. We demonstrated that three different cellular proteins (p70, p48, and p35/38) bound to the promoter sequence of the template RNA. Deletion analyses of the template RNA mapped the binding site of p35/38 at the consensus transcription initiation signal. In contrast, the binding of p70 and p48 was less specific. p35/38 is the same protein as the one previously identified to bind to the complementary strand of the leader RNA; its binding affinity to the leader was approximately 15 times stronger than that to IG7. Site-directed mutagenesis of the IG sequence revealed that mutations in the consensus sequence of IG7 (UCUAAUCUAAAC to UCGAAAC and GCUAAAG), which resulted in reduced subgenomic mRNA transcription, also caused correspondingly reduced levels of p35/38 binding. These results demonstrated that the extent of protein binding to the IG sequences correlated with the amounts of subgenomic mRNAs transcribed from the IG site. These studies suggest that these RNA-binding proteins are involved in coronavirus RNA transcription and may represent transcription factors.


docid: vyoudoja

title: Presence of genomic polyadenylate and absence of detectable virion transcriptase in human coronavirus OC-43.

text: Human coronavirus RNA, prepared by extraction of purified virions with phenol-chloroform, consists of a major 15 to 55S class and a minor 4S class of RNA fragments. Polyadenylic acid [poly (A)] sequences are present in 15 to 55S but not in 4S RNA, suggesting different functions for each class. A stretch of poly (A) of approximately 19 adenosine monophosphate residues was obtained in sizing experiments after digesting OC-43 RNA with pancreatic and T1 ribonucleases. An OC-43 virion RNA transcriptase could not be detected with systems optimal for detecting the transcriptases of influenza and Newcastle disease virus.


Severe acute respiratory syndrome: What have we learned two years later?


title: Early clinical predictors of severe acute respiratory syndrome in the emergency department.

text: OBJECTIVES To assess the association of diagnostic predictors available in the emergency department (ED) with the outcome diagnosis of severe acute respiratory syndrome (SARS). METHODS This retrospective cohort study describes all patients from the Amoy Garden complex who presented to an ED SARS screening clinic during a 2-month outbreak. Clinical and diagnostic predictors were recorded, along with ED diagnoses. Final diagnoses were established independently based on diagnostic tests performed after the ED visit. Associations of key predictors with the final diagnosis of SARS were described. RESULTS Of 821 patients, 205 had confirmed SARS, 35 undetermined SARS and 581 non-SARS. Multivariable logistic regression showed that the strongest predictors of SARS were abnormal chest x-ray (odds ratio [OR] = 17.4), subjective fever (OR = 9.7), temperature degrees >38 degrees C (OR = 6.4), myalgias (OR = 5.5), chills and rigors (OR = 4.0) and contact exposure (OR = 2.6). In a subset of 176 patients who had a complete blood cell count performed, the strongest predictors were temperature >or=38 degrees C (OR = 15.5), lymphocyte count <1000 (OR = 9.3) and abnormal chest x-ray (OR = 5.7). Diarrhea was a powerful negative predictor (OR = 0.03) of SARS. CONCLUSIONS Two components of the World Health Organization case definition - fever and contact exposure - are helpful for ED decision-making, but respiratory symptoms do not discriminate well between SARS and non-SARS. Emergency physicians should consider the presence of diarrhea, chest x-ray findings, the absolute lymphocyte count and the platelet count as significant modifiers of disease likelihood. Prospective validation of these findings in other clinical settings is desirable.


title: Vasculitis and anaphylactoid shock induced in mice by cell wall extract of the fungus Candida metapsilosis.

text: To investigate whether cell wall mannan from Candida metapsilosis induces vasculitis similar to that in Kawasaki syndrome and anaphylactoid shock in mice, we examined the pathogenic effects of C. metapsilosis cell wall extracts. Our results show that intraperitoneal injection of cell wall extracts induced severe coronary arteritis, and intravenous injection induced acute anaphylactoid shock similar to extracts from Candida albicans (C. albicans). Structural analysis of cell wall mannan from C. metapsilosis using NMR spectroscopy showed it to contain only a-mannan, indicating that a-mannan might be contributing to Candida pathogenicity by inducing coronary arteritis and acute shock.


title: Hyperoxygenated solutions in clinical practice: preventing or reducing hypoxic injury.

text: In cases of hypoxia, oxygen can be supplied via a number of methods including face masks, nasal cannulae, hyperoxygenated oxygen chambers and mechanical ventilation. Administering oxygen via the respiratory tract is, however, limited in respiratory diseases such as pulmonary fibrosis, pneumoconiosis and severe acute respiratory syndrome, or following the inhalation of asphyxiating poisons. This has led to research into new methods of supplying oxygen that bypass the lungs. Research has investigated the efficacy of intravenous hyperoxygenated solutions (HOS) as auxiliary oxygen supplies in several hypoxic states including cardiopulmonary resuscitation, respiratory failure, cerebrovascular disease, myocardial ischaemia, severe acute respiratory syndrome, poisoning, neonatal hypoxia, altitude sickness, large burns and traumatic haemorrhagic shock. Much of the research has taken place in China and more than 3.5 million hypoxic patients have received HOS, with good therapeutic effects. This review summarizes the literature supporting the use of this novel treatment.


Antigenic cross-reactivity between the nucleocapsid protein of severe acute respiratory syndrome (SARS) coronavirus and polyclonal antisera of antigenic group I animal coronaviruses: implication for SARS diagnosis.


title: Influence of the immune system on the course of infection with murine coronavirus JHM in suckling mice.

text: The course of infection with murine corona virus JHM in C3H mice depends on the age of the animals. Mice up to 20 days of age are fully susceptible while mice older than 23 days resist the infection. Protection of suckling mice from death of infection can be provided by intraperitoneal administration of immune spleen cells but not by non-immune spleen cells from adult mice. The immune spleen cells can be generated by priming adult mice, or by priming non-immune spleen cells from adult mice in baby mice with inactivated JHM virus. Thus the immune system might well be involved in the different outcome of infection with JHM-virus in suckling and adult mice, but it does not seem to be the exclusive factor responsible for the achievement of natural resistance.


title: Virus-associated hemophagocytic syndrome in an international traveler as a differential diagnosis of SARS.

text: During the epidemic of severe acute respiratory syndrome in 2003, a 27-year- old Japanese woman presented a high fever and acute respiratory distress with pulmonary infiltrates after traveling to a high-risk area. An alternative diagnosis was made as Epstein-Barr virus-associated hemophagocytic syndrome, based on the proliferation of macrophages with hemophagocytosis in the bone marrow and Epstein-Barr viral marker profiles. Virus-associated hemophagocytic syndrome in an international traveler should be included in the differential diagnosis of severe acute respiratory syndrome.


docid: klsfadho

title: The continuing story of dhat syndrome.


title: Studies on the epizootiology of canine coronavirus.

text: The seroprevalence and, or, incidence of canine coronavirus infection was determined in several dog populations in the UK. Seroprevalence ranged from 76 per cent for a rescue kennel to 100 per cent in a commercial breeding colony. In the rescue kennel there was no difference in seroprevalence of the virus between dogs less than or more than four months of age. In the breeding colony, subclinical seroconversion occurred between six and 10 weeks of age. The virus was isolated from faecal samples from 45 of 100 dogs in the rescue kennel; it was isolated from 73 per cent of the dogs with diarrhoea and from 43 per cent of those which did not have diarrhoea. In field cases of acute, mainly haemorrhagic diarrhoea in pet dogs, eight of 32 were positive for canine coronavirus. No canine coronavirus was isolated from either clinically healthy pet dogs in a boarding kennel or from non-diarrhoeic pet dogs examined at the University of Liverpool Small Animal Hospital. It would appear that although canine coronavirus is widespread, the role of the virus in canine enteritis is still equivocal.


Profile of specific antibodies to the SARS-associated coronavirus.


title: Molecular diagnostics of atypical pneumonia.

text: The emergence of nucleic acid-based molecular techniques has significantly enhanced laboratory diagnosis and monitoring of atypical pneumonia. These techniques have not only provided rapid and sensitive detection of fastidious microbial organisms but have also played critical roles in identifying and characterizing emerging pathogens that cause atypical pneumonia. Other benefits that molecular techniques can bring to the field include organism differentiation, quantitation, typing, and antibiotic resistance profiles. Gradually becoming standardized and widely available, the future will see some promising molecular methods become a mainstay in clinical laboratories for recognition and diagnosis of atypical pneumonia pathogens.


docid: bcdmfsec

title: Mandibular periostitis ossificans in immature large breed dogs: 5 cases (1999-2006).

text: This case series describes clinical, radiographic, and histopathological features of mandibular swellings in 5 immature, large breed dogs. The dogs originated from different regions of the United States. In each case, intraoral dental radiography of the jaw swelling revealed a two-layered (double) ventral mandibular cortex. Biopsy was performed in 4 of the 5 puppies, revealing periosteal new bone formation. Resolution of the mandibular swelling was spontaneous in the 4 dogs available for follow-up examination. The authors postulate that the clinical, radiographic, and histopathological presentation of mandibular swelling in these 5 dogs is a distinct pathological entity consistent with an inflammatory condition of the maturing human mandible known as periostitis ossificans.


title: Targeting IFN-λ: therapeutic implications.

text: INTRODUCTION Type-III interferons (IFN-λ), the most recently discovered family of IFNs, shares common features with other family members, but also has many distinctive activities. IFN-λ uniquely has a different receptor complex, and a more focused pattern of tissue expression and signaling effects, from other classes of IFNs. Multiple genome-wide association studies (GWAS) and subsequent validation reports suggest a pivotal role for polymorphisms near the IFNL3 gene in hepatitis C clearance and control, as also for several other epithelial cell tropic viruses. Apart from its antiviral activity, IFN-λ possesses anti-tumor, immune-inflammatory and homeostatic functions. The overlapping effects of IFN-λ with type I IFN, with a restricted tissue expression pattern renders IFN-λ an attractive therapeutic target for viral infection, cancer and autoimmune diseases, with limited side effects. Areas covered: This review will summarize the current and future therapeutic opportunities offered by this most recently discovered family of interferons. Expert opinion: Our knowledge on IFN-λ is rapidly expanding. Though there are many remaining questions and challenges that require elucidation, the unique characteristics of IFN-λ increases enthusiasm that multiple therapeutic options will emerge.


title: Severe acute respiratory syndrome: 'SARS' or 'not SARS'.

text: Accurate clinical diagnosis of severe acute respiratory syndrome (SARS) based on the current World Health Organization definition is difficult and at times impossible at the early stage of the disease. Both false positive and false negative cases are commonly encountered and this could have far-reaching detrimental effects on the patients, their family and the clinicians alike. Contact history is particularly important in diagnosing SARS in children as their presenting features are often non-specific. The difficulty in making a correct diagnosis is further compounded by the lack of a sensitive rapid diagnostic test. Serology is not particularly helpful in the initial triaging of patients as it takes at least 3 weeks to become positive. Co-infection and other treatable conditions should not be missed and conventional antibiotics should remain as part of the first-line treatment regimen. We report five cases to illustrate the difficulties and dilemmas faced by clinicians in diagnosing SARS in children.


Early intervention for first episode psychosis: secondary care must become more responsive to primary care.


title: [The genome comparison of SARS-CoV and other coronaviruses].

text: The genome comparison of inter-species and intra-species can give us much information about the origin and evolution of viruses. There are 137 mutation sites in the 17 genomes of SARS-CoV,and the mutation rate is about 8.04 x 10(-3) substitution/site/year. The distribution of the segregating sites is not steady,the most variable region appears in S1 protein,and the nucleotide sequence of RNA-dependent RNA polymerase has very few mutation sites. The substitution bias of nucleotide acids and amino acids indicates the non-random drift products. The comparison of genome structures of SARS-CoV and other coronaviruses shows that SARS-CoV and IBV share the same genome structure. Phylogenetic analyses of conserved genes of coronaviruses indicate that SARS-CoV is a new branch of coronaviruses and appears more close to the group II coronaviruses. Interestingly,SARS-CoV shares some different features with different groups of coronaviruses. Additional analyses show that the first ORFs between S and E genes of some coronaviruses are transmembrane proteins and share the common motif,indicating the possible common ancestor. From the host distribution of different groups of coronaviruses and the phylogeny of s2m,we can deduce that avian is the probable natural host of SARS-CoV.


docid: mefaofkc

title: [A case-control study on the mxA polymorphisms and susceptibility to severe acute respiratory syndromes].

text: OBJECTIVE To investigate the association between the genetic polymorphisms of myxovirus resistance 1 (MxA) gene and susceptibility to severe acute respiratory syndromes (SARS). METHODS A case-control study was conducted and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the T/G polymorphism at position-88 in the mxA gene promoter. Information on related factors of SARS was collected using a pre-testing questionnaire. Univariate and multivariate logistic analyses were conducted with SPSS software package. RESULTS Sixty-six cases and sixty-four controls were selected for the study. Comparing with GG genotype, the proportion of GT genotype were significantly higher in the case group (81.3%) than that in the control group (62.5%)) with an OR (95% CI) of 2.700 (1.208-6.037). Multivariate logistic regression analysis revealed that the significant association remained after factors as wearing masks, protection gowns and eye-protection when contacting with SARS patient etc. were adjusted with an OR (95 % CI) of 2.911 (1.027-8.250). CONCLUSION mxA promoter-88G/T SNP might be confered to host genetic susceptibility to SARS in Chinese Han population.


title: Monitoring temperature in children undergoing anaesthesia: a comparison of methods.

text: Children undergoing anaesthesia are prone to hypothermia. Perioperative monitoring of patient temperature is, therefore, standard practice. Postoperative temperature is regarded as a key anaesthetic performance indicator in Australian hospitals. Many different methods and sites of temperature measurement are used perioperatively. It is unclear to what degree these methods might be interchangeable. The aim of this study was to determine the relationships between temperatures measured at different sites in anaesthetised children. Two hundred children, 0 to 17 years, undergoing general anaesthesia for elective non-cardiac surgery, were prospectively recruited. Temperature measurements were taken in the operating theatre concurrently at the nasopharynx, tympanic membranes, temporal artery, axilla and skin (chest). Patient age and weight were documented. Temperatures varied according to site of measurement. The mean difference from nasopharyngeal temperature to temperatures at left and right tympanic, temporal, axillary and cutaneous sites were +0.24°C, +0.24°C, +0.35°C, -0.38°C and -1.70°C, respectively. Levels of agreement to nasopharyngeal temperature were similar at tympanic, temporal and axillary sites. Tympanic and temporal temperatures were superior to axillary temperatures for detection of mild hypothermia (<36°C). Skin temperature showed a large variation from nasopharyngeal measurements. Our findings indicate that measured temperatures vary between sites. Understanding these variations is important for interpreting temperature readings.


International health: five reasons why Canadians should get involved.


Coronavirus genomic-sequence variations and the epidemiology of the severe acute respiratory syndrome.


title: [Seasonal patterns of coronavirus infections in Hamburg].

text: During a serological surveillance programme between October 1974 and September 1975 in Hamburg, 1624 sera from all age groups of the population were examined for the presence of coronavirus antibodies (OC 43 agent). 61,51% of the sera showed HI-titres between 1:8 and 1:128. The geometric mean antiboty titre (GMT) for the whole group was 1:12,2. The serological seasonal pattern suggests that coronaviruses are circulating the whole year in the urban population with a prevalence in the cold and a decrease in the warm season (June). The highest incidence of seropositive reactions (82,9%) was found in the 15-24 years old individuals (GMT 1:13,8). These data indicate an increased spread of coronaviruses in this segment of the population and a marked susceptibility of the group.


title: Infection by coronavirus JHM of rat neurons and oligodendrocyte-type-2 astrocyte lineage cells during distinct developmental stages.

text: Primary telencephalic cultures derived from neonatal Wistar Furth rats were able to support the growth of coronavirus JHM if a viable neuronal population was maintained. This occurred under serum-free defined, but not serum-supplemented, growth conditions. The importance of neurons in establishing infections in mixed cultures was confirmed by immunocytochemical and electron microscopic studies. Glia, although more abundant than neurons in these cultures, were less frequently infected during the initial 48 h postinoculation. The two glial lineages present in mixed telencephalic cultures were separated into type-1 astrocytes and oligodendrocyte-type-2 astrocyte (O-2A) lineage cells and individually assessed for their ability to support virus growth. Infection could not be established in type-1 astrocytes regardless of the culture conditions employed, consistent with our previous study (S. Beushausen and S. Dales, Virology 141:89-101, 1985). In contrast, infections could be initiated in selected O-2A lineage cells grown in serum-free medium. Virus multiplication was however significantly reduced by preconditioning the medium with mixed telencephalic or enriched type-1 astrocyte cultures, suggesting that intercellular interactions mediated by soluble factor(s) can influence the infectious process in O-2A lineage cells. This presumption was supported by eliciting similar effects with basic fibroblast growth factor and platelet-derived growth factor, two central nervous system cytokines known to control O-2A differentiation. The presence of these cytokines, which synergistically block O-2A cells from differentiating into oligodendrocytes was correlated with specific and reversible resistance to JHM virus (JHMV) infection. These data, combined with our finding that accelerated terminal differentiation of the oligodendrocyte phenotype confers resistance to JHMV (Beushausen and Dales, Virology, 1985), suggest that the permissiveness of O-2A cells for JHMV is restricted to a discrete developmental stage.


title: Characterization of virus isolates by particle-associated nucleic acid PCR.

text: Diagnostic virus isolation is still frequently used, particularly from respiratory tract secretions. Testing positive virus cultures for all possible viruses is time-consuming, and unexpected or unknown viruses may escape detection. Therefore, a novel random PCR approach was developed that allows sequence-independent amplification of viral nucleic acids from virus isolation-positive cultures. Selectivity for viral sequences is obtained by preferential isolation of nucleic acids that are particle associated and resistant to nucleases. Using primers with a degenerated 3' end, the isolated nucleic acids are amplified and the randomly amplified PCR products are cloned and sequenced. As proof of the concept, the PAN-PCR approach was applied to supernatants of coxsackievirus B3 and murine adenovirus type 1-infected cells. Enterovirus and adenovirus sequences were obtained, demonstrating that the random PCR approach allows detection of RNA and DNA viruses. As a first application of this PAN-PCR approach, we characterized a virus isolate from mouth-washing material of a patient with chronic fatigue syndrome and high antibody titers to coxsackievirus B2. The virus isolate had tested negative for enteroviruses and respiratory viruses (influenza viruses A and B, parainfluenza virus types 1 to 3, respiratory syncytial virus, and adenovirus) by immunofluorescence and PCR. Particle-associated, nuclease-resistant RNA and DNA were prepared from the supernatant of infected cells. The DNA and the reverse-transcribed RNA were randomly amplified, and PCR products were cloned and sequenced. Of 25 sequences obtained from the DNA preparation, 24 contained herpes simplex virus type 1 (HSV-1) sequences from 14 different loci spread over the HSV-1 genome. This result was confirmed by using a standard diagnostic HSV-PCR, demonstrating that the PAN-PCR correctly identified the virus isolate. Although the identification of HSV-1 in mouth-washing material is not surprising in retrospect, it clearly demonstrates the applicability of the PAN-PCR approach. This method should be particularly useful for characterizing virus isolates that have tested negative for all expected viruses and for identifying unknown viruses.


title: Etiology, diagnosis, and antimicrobial treatment of pharyngitis and pharyngotonsillitis.

text: This review focuses on clinically important aspects of the etiology, diagnosis, and antimicrobial treatment of pharyngitis and pharyngotonsillitis. Most episodes of throat infection are of viral etiology, and accordingly are not susceptible to antimicrobial drugs currently available. By contrast, streptococcal and other varieties of bacterial pharyngitis do call for appropriate antimicrobial treatment. The review encompasses a discussion of clinical, bacteriological, and serological diagnosis; an algorithm for decision-making about antimicrobial treatment that is based on both clinical findings and culture results; and a summary of treatment regimens, emphasizing the management of streptococcal throat infection.


title: Ileocecocolic strictures in two captive cheetahs (Acinonyx jubatus jubatus).

text: Intestinal strictures were diagnosed in two captive cheetahs (Acinonyx jubatus jubatus). The cheetahs presented with lethargy, anorexia, diarrhea, and weight loss. The first cheetah had a stricture of the ileocecocolic junction diagnosed at necropsy. The second had an ileocecocolic stricture causing obstruction that was diagnosed at surgery. After resection and anastomosis, the cheetah recovered well. The etiology of the strictures remains undetermined. Intestinal stricture, particularly of the ileocecocolic junction, should be considered as a differential diagnosis for cheetahs with nonspecific gastrointestinal signs.


docid: ttysqmta

title: Pathogenesis of coronavirus SD in mice. I. Prominent demyelination in the absence of infectious virus production.

text: Following intracerebral inoculation of 3- to 4-week-old C57 B16/J mice with coronavirus SD, 23% exhibited neurologic signs within the first week. However, only 6% died. Within the first week after inoculation (AI), we noted a panencephalitis. Prominent demyelination detected in the spinal cord on day 6 continued through day 29 AI. Demyelinated lesions in the spinal cord were either subpial with few inflammatory cells except for macrophages or perivascular with prominent accumulation of lymphocytes, plasma cells, and macrophages. Beginning on day 6 AI, IgG was detected in the lesions. Although an infectious virus was detectable in the CNS only through day 12 AI, viral antigen expression continued through day 24. We concluded that coronavirus SD persists in a nonrecoverable form throughout the initial phase of demyelination, day 6 to day 24 AI.


title: [The possible mechanism of lung injury induced by severe acute respiratory syndrome coronavirus spike glycoprotein].

text: OBJECTIVE To investigate the role of severe acute respiratory syndrome coronavirus (SARS-CoV) in the induction of acute lung injury by promoting the synthesis of chemokine/cytokines in human endothelial cells. METHODS Twenty-three SARS patients were enrolled in this study, comprising 15 male and 8 female, aged 27 - 55 years, mean (36 +/- 6) years. They were treated at Guangzhou Institute of Respiratory Disease from February to May in 2003. Chemokines/cytokines in the blood of patients with SARS were dynamically screened by liquid chip system. The lung was studied histopathologically using immunohistochemical technique. Spike glycoprotein of SARS-CoV was recombined by using insect-baculovirus expression system and Nickel affinity Magnet Beads, and then used to stimulate cultured human umbilical vein endothelial cells (HUVEC). Morphological changes of HUVEC were observed by microscope. Levels of chemokines/cytokines involved in immunoreaction in response to virus infection were detected in the supernatants of those cells cultured with the Spike glycoprotein by liquid chip system. RESULTS Interferon-gamma inducible protein 10 (IP-10) was markedly elevated in the blood during the early stage of SARS [(7,600 +/- 2,400) ng/L, P < 0.01], and remained at a high level in the progressive stage [(8,100 +/- 2,300) ng/L, P < 0.01] and the end stage [(8,000 +/- 2,800) ng/L, P < 0.01] until convalescence [(1,250 +/- 450) ng/L, P > 0.05]. Moreover, IP-10 was highly expressed in the lung. Vacuoles appeared in part of HUVEC after Spike glycoprotein stimulation. As time going on, the HUVEC turned to be round in shape and even disrupted. Under normal condition, no detectable IP-10 was found in HUVEC. A high level of IP-10 [(179 +/- 34), (889 +/- 212), (1,676 +/- 199) ng/L, all P < 0.05] was detected in the HUVEC 12 h after Spike glycoprotein (5, 20, 40 mg/L) stimulation respectively, and presented with a significant dose-dependent response. CONCLUSIONS (1) A significant increase of IP-10 activity in the blood was found in patients with SARS-CoV infection, and remained at a high level until the stage of convalescence. A strong IP-10 protein expression was also found in SARS-CoV infected lung in autopsy. (2) The Spike glycoprotein of SARS-CoV induced a high level of IP-10 in endothelial cells, which in turn damaged endothelial cells. (3) The Spike glycoprotein of SARS-CoV induced IP-10 production by a way independent of IFN-gamma.


title: [Monitoring of viral pathogens in pediatric intensive care unit and analysis of clinical significance].

text: OBJECTIVE To study the characteristics of viral spectrum and clinical features of children in pediatric intensive care unit (PICU). METHOD Nasopharyngeal aspirate specimens (NPA) from 349 patients(1 from each) and 130 cerebrospinal fluids (CSF) specimens were collected from children who were admitted to the PICU of Second Affiliated Hospital of Shantou University Medical College. Additional 87 NPA specimens were collected from healthy children for routine examination on the physical examination center, and the clinical data were collected. Multiplex PCR was applied to detect 16 kinds of viruses from NPA and CSF. Fluorescence quantitative PCR was applied to detect 13 viruses from CSF and to analyze the clinical data of positive cases. RESULT There were 209 samples (59.9%) of the 349 NPA specimens were positive for viruses, which included 117 cases positive for human rhinovirus (HRV), 60 for respiratory syncytial virus (RSV), 20 for influenza virus A (Inf A), 10 for adenovirus (ADV), 6 for parainfluenza virus type 3(PIV-3), 6 for human Boca virus (HBoV), 5 for influenza virus C(Inf C), 4 for parainfluenza virus type 4(PIV-4), 4 for human coronavirus-HKU1/OC43, 3 for influenza virus B (Inf B), 3 for WU Polyomavirus (WUPyV), 2 parainfluenza virus type 1(PIV-1), 2 human metapneumovirus (HMPV) and 1 human coronavirus-NL63/229E. But none from 87 healthy controls were positive for any respiratory virus. Among the 130 CSF specimens, in 58 cases the diagnosis was viral encephalitis. There were 22 samples (37.9%) among the 58 CSF specimens positive for viruses, which included 14 enterovirus (EV), 3 human cytomegalovirus (HCMV), 2 mumps virus, 1 coxsackie virus A16 (Cox-A16), 1 herpes simplex virus (HSV) and 1 human rhinovirus (HRV). The total positive rate was 63.3% (221/349) . Co-infection by at least 2 viral pathogens under study was observed in 45 of the 349 patients (12.9% of the total number of cases, 20.4% of the positives cases). The commonest pathogens in co-infected samples were WUPyV (100%) and HMPV(100%). The positive rate of virus peaked in the first 6 months of life, the rate in boys were higher than in girls and the peak season was summer. The numbers of none serious cases in the virus positive group were less than those in the virus negative group while the numbers of extremely serious cases in the virus positive group were higher than in the virus negative group. CONCLUSION Viral pathogen is a major cause of infectious disease in pediatric critical illnesses and virus infection may lead to severe illness.


title: Awareness of stroke warning symptoms--13 States and the District of Columbia, 2005.

text: Although the number of deaths from stroke has declined substantially since the 1960s, in 2004, stroke remained the third leading cause of death in the United States, after heart disease and cancer. Approximately 54% of U.S. stroke deaths in 2004 occurred outside of a hospital. Intravenous administration of tissue plasminogen activator has clinical benefits for patients with acute ischemic stroke; however, treatment should begin within 3 hours of symptom onset for these benefits to be realized. For hemorrhagic stroke, immediate surgery (e.g., aneurysm repair) is crucial to prevent rebleeding that results in serious impairment or death in 40% to 60% of cases. A revised objective of Healthy People 2010 is to increase to 83% the proportion of persons who are aware of the warning symptoms of stroke and the need to telephone 9-1-1 immediately if someone appears to be having a stroke (objective no. 12-8). To assess public awareness of stroke warning symptoms and the importance of seeking emergency care, CDC analyzed data from an optional module of the 2005 Behavioral Risk Factor Surveillance System (BRFSS) survey that was used in 13 states and the District of Columbia (DC). The results indicated that the percentages of respondents who recognized all five correct symptoms, identified an incorrect symptom, and recognized the need to telephone 9-1-1 was low; the percentage who met all three measures was 16.4%. In addition, disparities were observed by race/ethnicity, sex, and education level. Public health agencies, clinicians, and educators should continue to stress the importance of learning to recognize stroke symptoms and the need to telephone 9-1-1 when someone appears to be having a stroke.


title: Isotype-specific antibody-secreting cells to transmissible gastroenteritis virus and porcine respiratory coronavirus in gut- and bronchus-associated lymphoid tissues of suckling pigs.

text: Antibody-secreting cells (ASC) were enumerated in gut- and bronchus-associated lymphoid tissues of pigs exposed to three antigenically related coronaviruses: virulent transmissible gastroenteritis virus (TGEV), attenuated TGEV, and porcine respiratory coronavirus (PRCV). Exposure of 11-day-old pigs to virulent TGEV resulted in severe gastroenteritis and virus shedding mainly in feces but also to a limited extent in nasal secretions. PRCV and attenuated TGEV exposure produced no clinical signs and only one pig given a high dose of attenuated TGEV shed virus in feces, but virus was shed from the nasal passages. Nasal virus titers were highest after PRCV inoculation of pigs. Mononuclear cells were isolated from spleens, mesenteric, and bronchial lymph nodes of pigs and assayed for virus-specific IgG and IgA antibody secretion by an enzyme-linked immunospot assay. Virus-specific ASC peaked at postinoculation days 12 to 24 and IgG-ASC outnumbered IgA-ASC in all tissues tested. The greatest numbers of ASC were in mesenteric lymph nodes of virulent TGEV-exposed pigs and in BLN of PRCV-exposed pigs. Attenuated TGEV induced intermediate ASC responses in the gut and respiratory tract. Secondary in vitro ASC responses to inactivated TGEV or PRCV paralleled the primary responses except in BLN where the numbers of memory ASC were high for both TGEV- and PRCV-exposed pigs. We conclude that: 1) a single exposure of pigs to PRCV either oral-nasally or by aerosol leads to potent systemic and bronchus-associated, but not gut-associated, ASC responses; 2) a high dose of attenuated TGEV (4 x 10(8) plaque-forming units) is more effective than PRCV (6 x 10(5) or 2 x 10(8) plaque-forming units) or a lower dose of attenuated TGEV (7 x 10(6) plaque-forming units) in eliciting gut-associated ASC; 3) although virulent and a high dose of attenuated TGEV induce high numbers of ASC in the tissues tested, virulent TGEV induces the most ASC in the gut and IgA-ASC in all lymphoid tissues; and 4) virus replication in the gut or respiratory tract is a major factor affecting the magnitude of an ASC response at that site and may be necessary for the recruitment of IgG- and IgA-ASC and memory cells in large numbers from other mucosal inductive sites. This unique model of mucosal immunity using antigenically related viruses with distinct tissue tropisms may help to clarify interactions of the various components of the common mucosal immune system.


title: Important role for the transmembrane domain of severe acute respiratory syndrome coronavirus spike protein during entry.

text: The spike protein (S) of severe acute respiratory syndrome coronavirus (SARS-CoV) is responsible for receptor binding and membrane fusion. It contains a highly conserved transmembrane domain that consists of three parts: an N-terminal tryptophan-rich domain, a central domain, and a cysteine-rich C-terminal domain. The cytoplasmic tail of S has previously been shown to be required for assembly. Here, the roles of the transmembrane and cytoplasmic domains of S in the infectivity and membrane fusion activity of SARS-CoV have been studied. SARS-CoV S-pseudotyped retrovirus (SARSpp) was used to measure S-mediated infectivity. In addition, the cell-cell fusion activity of S was monitored by a Renilla luciferase-based cell-cell fusion assay. S(VSV-Cyt), an S chimera with a cytoplasmic tail derived from vesicular stomatitis virus G protein (VSV-G), and S(MHV-TMDCyt), an S chimera with the cytoplasmic and transmembrane domains of mouse hepatitis virus, displayed wild-type-like activity in both assays. S(VSV-TMDCyt), a chimera with the cytoplasmic and transmembrane domains of VSV-G, was impaired in the SARSpp and cell-cell fusion assays, showing 3 to 25% activity compared to the wild type, depending on the assay and the cells used. Examination of the oligomeric state of the chimeric S proteins in SARSpp revealed that S(VSV-TMDCyt) trimers were less stable than wild-type S trimers, possibly explaining the lowered fusogenicity and infectivity.


title: Antiviral activity of nucleoside analogues against SARS-coronavirus (SARS-coV).

text: The recent outbreak of severe acute respiratory syndrome (SARS), which is an acute respiratory illness, is caused by newly discovered SARS coronavirus (SARS-CoV). Herein we describe the antiviral activity of several classes of nucleoside analogues evaluated against SARS-CoV in Vero 76 cells, some of which exhibited moderate activity.


title: Proteolytic maturation of replicase polyprotein pp1a by the nsp4 main proteinase is essential for equine arteritis virus replication and includes internal cleavage of nsp7.

text: The positive-stranded RNA genome of the arterivirus Equine arteritis virus (order Nidovirales) encodes the partially overlapping replicase polyproteins pp1a (1727 aa) and pp1ab (3175 aa). Previously, three viral proteinases were reported to cleave these large polyproteins into 12 non-structural proteins (nsps). The chymotrypsin-like viral main proteinase residing in nsp4 is responsible for eight of these cleavages. Processing of the C-terminal half of pp1a (the nsp3-8 region) was postulated to occur following either of two alternative proteolytic pathways (the 'major' and 'minor' pathways). Here, the importance of these two pathways was investigated by using a reverse-genetics system and inactivating each of the cleavage sites by site-directed mutagenesis. For all of these pp1a cleavage sites, mutations that prevented cleavage by the nsp4 proteinase were found to block or severely inhibit EAV RNA synthesis. Furthermore, our studies identified a novel nsp4 cleavage site (Glu-1575/Ala-1576) that is located within nsp7 and is conserved in arteriviruses. The N-terminal nsp7 fragment (nsp7alpha) derived from this cleavage was detected in lysates of both EAV-infected cells and cells transiently expressing pp1a. Mutagenesis of the novel cleavage site in the context of an EAV full-length cDNA clone proved to be lethal, underlining the fact that the highly regulated, nsp4-mediated processing of the C-terminal half of pp1a is a crucial event in the arterivirus life cycle.


title: Fospropofol, a new sedative anesthetic, and its utility in the perioperative period.

text: Fospropofol is an intravenous sedative-anesthetic agent that is FDA-approved for monitored anesthesia care (MAC) sedation in adult patients undergoing diagnostic or therapeutic procedures. As a prodrug of propofol, fospropofol's pharmacologic activity results from its breakdown by alkaline phosphatase and release of propofol, which is the active molecule. It exhibits a longer time to peak clinical effect and a more prolonged action compared to propofol. Thus patients may exhibit smoother hemodynamic and respiratory depression compared to propofol lipid emulsion bolus. Another advantage over propofol is that it does not induce a burning sensation on IV administration. Side effects include perineal paresthesia and itching, respiratory depression, hypoxemia, hypotension, loss of consciousness, and apnea with higher IV boluses. Therefore, current recommendations call for it to be administered only by clinicians trained in general anesthesia, who are thus skilled in advanced airway management. Fospropofol has a unique dosing regimen, with a standard dose for adults 18-65 years of age, and a modified dose (75% of the standard dose) for patients > 65 years of age and for sicker adult patients whose American Society of Anesthesiologists physical status score is ≥ 3. Also, the minimum and maximun IV bolus doses are body-weight adjusted to 60 and 90 kg respectively. Available evidence demonstrates that fospropofol in MAC sedation is successful in patients undergoing esophagogastroscopy, colonoscopy and flexible bronchoscopy. The use of fospropofol is also now being explored in many other perioperative settings. In light of current shortages of many anesthetic drugs, whether forspropofol can take the place of propofol in ICUs and operating rooms remains to be determined.


[Ⅱ.Strategy of Treatment for Untreated Transplant-Ineligible Multiple Myeloma].


title: Detection of PARV4, genotypes 1 and 2, in healthy and pathological clinical specimens.

text: The molecular epidemiology and tissue distribution of Human Parvovirus 4 (PARV4) and its variant PARV5 (Parvoviridae family) are poorly known. The aim of this study was to investigate the epidemiological role and prevalence of PARV4/5 by a nested-PCR on different clinical specimens, including blood samples from healthy donors, healthy and pathological skin samples, and bronchoalveolar lavages (BAL). Among blood specimens, 2/53 were positive; 3/37 and 23/105 of healthy and pathological skin specimens resulted positive, respectively, whereas no BAL was positive. PARV4/5 may be present in different healthy and pathological samples, suggesting the need for further investigating its tissue distribution.


title: A comparison of a traditional endotracheal tube versus ETView SL in endotracheal intubation during different emergency conditions: A randomized, crossover cadaver trial.

text: BACKGROUND Airway management is a crucial skill essential to paramedics and personnel working in Emergency Medical Services and Emergency Departments: Lack of practice, a difficult airway, or a trauma situation may limit the ability of paramedics to perform direct laryngoscopy during cardiopulmonary resuscitation. Videoscope devices are alternatives for airway management in these situations. The ETView VivaSight SL (ETView; ETView Ltd., Misgav, Israel) is a new, single-lumen airway tube with an integrated high-resolution imaging camera. To assess if the ETView VivaSight SL can be a superior alternative to a standard endotracheal tube for intubation in an adult cadaver model, both during and without simulated CPR. METHODS ETView VivaSight SL tube was investigated via an interventional, randomized, crossover, cadaver study. A total of 52 paramedics participated in the intubation of human cadavers in three different scenarios: a normal airway at rest without concomitant chest compression (CC) (scenario A), a normal airway with uninterrupted CC (scenario B) and manual in-line stabilization (scenario C). Time and rate of success for intubation, the glottic view scale, and ease-of-use of ETView vs. sETT intubation were assessed for each emergency scenario. RESULTS The median time to intubation using ETView vs. sETT was compared for each of the aforementioned scenarios. For scenario A, time to first ventilation was achieved fastest for ETView, 19.5 [IQR, 16.5-22] sec, when compared to that of sETT at 21.5 [IQR, 20-25] sec (p = .013). In scenario B, the time for intubation using ETView was 21 [IQR, 18.5-24.5] sec (p < .001) and sETT was 27 [IQR, 24.5-31.5] sec. Time to first ventilation for scenario C was 23.5 [IQR, 19-25.5] sec for the ETView and 42.5 [IQR, 35-49.5] sec for sETT. CONCLUSIONS In normal airways and situations with continuous chest compressions, the success rate for intubation of cadavers and the time to ventilation were improved with the ETView. The time to glottis view, tube insertion, and cuff block were all found to be shorter with the ETView. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT02733536.


title: The 2009 pandemic in Mexico: Experience and lessons regarding national preparedness policies for seasonal and epidemic influenza.

text: Influenza is a viral respiratory disease capable of causing epidemics that represent a threat for global security. Mexico was the first country to notify the WHO of an outbreak of what later became the first influenza pandemic of the 21st Century, caused by the virus A(H1N1)2009. Before this event Mexico had a national pandemic influenza preparedness plan, which included seasonal influenza vaccination, stockpiles of personal protection equipment and strategic drugs, and risk communication strategies. During the epidemic, the national public health laboratory network and case surveillance systems were strengthened together with surge capacities for intensive care and delivery of antiviral drugs. Risk communication was conducted for people to comply with implemented measures regarding social distancing (workplace and school closures, household quarantine). This report describes the Mexican experience during the 2009 influenza pandemic and the lessons that this experience provides to public health preparedness for future pandemics.


title: The internal open reading frame within the nucleocapsid gene of mouse hepatitis virus encodes a structural protein that is not essential for viral replication.

text: The coronavirus mouse hepatitis virus (MHV) contains a large open reading frame embedded entirely within the 5' half of its nucleocapsid (N) gene. This internal gene (designated I) is in the +1 reading frame with respect to the N gene, and it encodes a mostly hydrophobic 23-kDa polypeptide. We have found that this protein is expressed in MHV-infected cells and that it is a previously unrecognized structural protein of the virion. To analyze the potential biological importance of the I gene, we disrupted its expression by site-directed mutagenesis using targeted RNA recombination. The start codon for I was replaced by a threonine codon, and a stop codon was introduced at a short interval downstream. Both alterations created silent changes in the N reading frame. In vitro translation studies showed that these mutations completely abolished synthesis of I protein, and immunological analysis of infected cell lysates confirmed this conclusion. The MHV I mutant was viable and grew to high titer. However, the I mutant had a reduced plaque size in comparison with its isogenic wild-type counterpart, suggesting that expression of I confers some minor growth advantage to the virus. The engineered mutations were stable during the course of experimental infection in mice, and the I mutant showed no significant differences from wild type in its ability to replicate in the brains or livers of infected animals. These results demonstrate that I protein is not essential for the replication of MHV either in tissue culture or in its natural host.


title: Coronavirus infections in the laboratory rat: degree of cross protection following immunization with a heterologous strain.

text: One hundred and twenty-one specific pathogen-free male Wistar rats eight to ten weeks of age were used to evaluate the efficacy of Parker's rat coronavirus (PRC) in affording cross protection on subsequent challenge with virulent sialodacryoadenitis (SDA) virus. Sixty-two animals were inoculated intranasally on day 0 and 21 days later with approximately 10(2) median tissue culture infective doses (TCID50) of the tenth passage of PRC replicated in L-2 cells. Animals were selected at random postvaccination to evaluate the safety and efficacy of PRC by histopathology, immunohistochemistry and serology. At three and six months postvaccination (PV), vaccinated and seronegative control rats were inoculated intranasally with approximately 10(3) TCID50 doses of virulent SDA virus. Challenged rats were then killed at 6, 10 and 14 days postchallenge and necropsied. Evaluations were based on lesion indices in lacrimal and salivary glands and respiratory tract, the presence of viral antigen by immunohistochemistry, and antibody response. Lesions were observed in rats killed PV, but in general, they were significantly reduced compared with those present in seronegative animals post-exposure to virulent SDA virus (p < or = 0.05). However, they were still considered to be an unacceptable level for a routine vaccination procedure. Potvaccination antibody titers to rat coronavirus were evident in all animals tested at three or six months prior to challenge with SDA virus.(ABSTRACT TRUNCATED AT 250 WORDS)


title: Isolation of Trypanosoma (Megatrypanum) theileri from dairy cattle in Taiwan.

text: Although Trypanosoma (Megatrypanum) theileri, a blood parasite of bovid species, is spread widely throughout the world, it has never been reported in Taiwan. When an anti-coagulated blood sample from febrile dairy cattle was directly smeared, no parasite was observed. However, a highly distinctive morphological feature of trypanosome appeared in baby hamster kidney (BHK) cell culture inoculated with non-thrown blood buffy coat. The different stages and typical ultrastructures of trypanosome were observed in our isolate. The isolate was subsequently identified as T. theileri by species-specific PCR assay (Tth625), 18S rDNA sequencing alignment and internal transcribed spacer of ribosomal genes (ITS) as a marker for molecular phylogenetic analysis. The first T. theileri isolate in Taiwan (TWTth1) could be periodically passaged in BHK cell culture for more than one year and retained good re-cryopreservation viability. The BHK culture method would be excellent for diagnostic isolation and maintenance long-term development of this parasite.


docid: odkqjchd

title: The use of antibodies in the treatment of infectious diseases.

text: There is a long history of the use of antibodies in the treatment and prophylaxis of infectious diseases, because these molecules play a critical role in directing the effector mechanisms of the immune system against the pathogens they recognise. However, the widespread application of this therapy has been hampered by allergic reactions, production costs and the availability of alternative drugs such as antibiotics. Some of these obstacles can now be overcome with advances in biotechnology, which has enabled the development of antibody-based drugs for use first in treating cancer, and recently, for treating infectious diseases. The efficacy of such antibodies has been demonstrated in various in vitro studies, animal models and clinical trials for a variety of both viral and bacterial pathogens. Antibodies appear to hold great promise as a new class of drugs against infectious diseases.


title: Only one protomer is active in the dimer of SARS 3C-like proteinase.

text: The severe acute respiratory syndrome coronavirus 3C-like protease has been proposed to be a key target for structurally based drug design against SARS. The enzyme exists as a mixture of dimer and monomer, and only the dimer was considered to be active. In this report, we have investigated, using molecular dynamics simulation and mutational studies, the problems as to why only the dimer is active and whether both of the two protomers in the dimer are active. The molecular dynamics simulations show that the monomers are always inactive, that the two protomers in the dimer are asymmetric, and that only one protomer is active at a time. The enzyme activity of the hybrid severe acute respiratory syndrome coronavirus 3C-like protease of the wild-type protein and the inactive mutant proves that the dimerization is important for enzyme activity and only one active protomer in the dimer is enough for the catalysis. Our simulations also show that the right conformation for catalysis in one protomer can be induced upon dimer formation. These results suggest that the enzyme may follow the association, activation, catalysis, and dissociation mechanism for activity control.


title: Immune response in sows given transmissible gastroenteritis virus or canine coronavirus.

text: Twelve pregnant sows were inoculated oral-nasally 8 weeks before farrowing with attenuated transmissible gastroenteritis virus (TGEV), tissue culture-adapted canine coronavirus (CCV), or fluids from mock-infected culture (controls). A 2nd dose of the same inoculum, one-half oral-nasally and one-half intramammarily, was given 6 weeks later. Neutralizing antibodies for TGEV and CCV were demonstrated in sera, colostrum, and milk whey from the virus-vaccinated sows. Homologous geometric mean neutralizing titers were generally 4-fold higher than were heterologous titers. After challenge exposure of the nursing pigs with virulent TGEV, average morbidity and mortality for the pigs were 81% and 34% (mortality range = 11% to 63%), respectively, in the TGEV-vaccinated group; 83% and 39% (mortality range = 15% to 83%), respectively, in the CCV-vaccinated group; and 97% and 84% (mortality range = 78% to 100%), respectively, in the controls. Seemingly, sera from swine exposed to CCV could test serologically positive for TGEV-neutralizing antibody, and TGEV and CCV share at least 1 common neutralizing determinant that may be involved in protection.


title: What is new in infectious diseases: Nipah virus, MERS-CoV and the Blueprint List of the World Health Organization.

text: Not available.


title: HPB Online: an electronic health education portal in Singapore.

text: In 2001, the Health Promotion Board (HPB) developed HPB Online, an internet-based health education portal to disseminate health messages. The objective of this article is to describe the structure of HPB Online, review its reach as a tool to deliver health information in Singapore, and discuss the advantages of using the internet to complement traditional media such as the television, newspapers and radio. Since its inception in 2001, the numbers of page-views, monthly visits and repeat visitors have increased markedly. The most popular webpages have consistently been Food Info Search. The average length of visit also showed a gradual increase during the study period, from about 11.0 minutes in January 2002 to 18.5 minutes in December 2004. The key advantage of using the HPB Online is that it allows quick delivery of information to the public and this is ideal for time-sensitive issues. It helps Singaporeans to make better informed decisions to maintain and to improve their health. With its high utilisation, the HPB will continue to use the internet as part of its multichannel marketing strategy to disseminate health information.


title: Transitional cell carcinomas in four fishing cats (Prionailurus viverrinus).

text: Transitional cell carcinomas (TCC) of the urinary bladder were diagnosed in four related fishing cats (Prionailurus viverrinus). The major clinical sign in each case was persistent hematuria unresponsive to medical therapy. Cystotomy and biopsy provided an antemortem diagnosis in three of the fishing cats before euthanasia because of progression of clinical signs. The diagnosis was made in the fourth cat after euthanasia because of renal failure. Hematuria improved temporarily in one of the cats diagnosed antemortem and treated with piroxicam and carboplatin. Attempts to isolate a herpesvirus in two of the cats failed. Histopathologic appearance of the TCC was similar to that described for other species. TCC metastasis to the lungs was noted at necropsy in one cat; metastatic disease was not noted in the other fishing cats on gross or histopathologic examination. TCC of the urinary bladder appears to be more prevalent in fishing cats than in other species of domestic or nondomestic felids.


title: [Anesthesia management in cesarean section for a patient with coronavirus disease 2019].

text: Since the corona virus disease 2019 (COVID-19) affects the cardio-pulmonary function of pregnant women, the anesthetic management in the cesarean section for the patients, as well as the protection for medical staff is significantly different from that in ordinary surgical operation. This paper reports a pregnant woman with COVID-19, for whom a cesarean section was successfully performed in our hospital on February 8, 2020. Anesthetic management, protection of medical staff and psychological intervention for the patients during the operation are discussed. Importance should be attached to the preoperative evaluation of pregnant women with COVID-19 and the implementation of anesthesia plan. For ordinary COVID-19 patients intraspinal anesthesia is preferred in cesarean section, and the influence on respiration and circulation in both maternal and infant should be reduced; while for severe or critically ill patients general anesthesia with endotracheal intubation should be adopted. The safety of medical environment should be ensured, and level-Ⅲ standard protection should be taken for anesthetists. Special attention and support should be given to maternal psychology. It is important to give full explanation before operation to reduce anxiety; to relieve the discomfort during operation to reduce tension; to avoid the bad mood of patients due to pain after operation.


Quantitation, phenotypic characterization and in situ localization of lymphoid cells in the brain parenchyma of rats with differing susceptibility to coronavirus JHM-induced encephalomyelitis.


title: Importance of truncal-type occlusion in stentriever-based thrombectomy for acute stroke.

text: OBJECTIVE To investigate whether angiographically defined occlusion type could predict of the etiology of acute intracranial large artery occlusion and the stentriever response. METHODS We reviewed consecutive patients with acute intracranial large artery occlusion who underwent endovascular treatment and examined their workups for embolic sources. Patient demographics, laboratory findings, hyperdense artery sign, and angiographic occlusion type (truncal-type or branching-site occlusion) were compared between embolic sources (+) and (-) groups. These variables were also compared between stentriever failure and success groups. Details of endovascular procedures were also compared according to occlusion type. RESULTS A total of 259 patients (mean age 70.3 years; M:F = 132:127) were finally included. Of these patients, 216 (83.4%) were assigned to the embolic sources (+) group after thorough evaluation. Young age, no coronary artery disease, and truncal-type occlusion (odds ratio [OR] 9.07; 95% confidence interval [CI] 3.74-22.0) were independently associated with the embolic source (-) group. Of the overall group, 224 patients (86.5%) underwent stentriever-based endovascular treatment. Hypertension, diabetes, high C-reactive protein level, and truncal-type occlusion (OR 32.2; 95% CI 7.78-133.0) were independent predictors of stentriever failure. Truncal-type occlusion was associated with more reocclusion (77.3% vs 5.0%), resulting in recanalization failure by the stentriever (81.8% vs 20.3%), a longer puncture-to-recanalization time (118.0 vs 49.5 minutes), and more rescue treatment for final successful recanalization (78.9% vs 7.0%). CONCLUSIONS Angiographic occlusion type is an independent predictor of stentriever refractoriness and of the underlying stroke mechanism.


title: [The experimental coronavirus infection of monkeys].

text: The coronavirus (CV) infection has been reproduced on monkeys (Macaca mulatta) for the first time. The strain CVRM 281, obtained from rhesus monkey who died of the spontaneous CV injection, has been used for the infection. The experimental CV infection has a chronic current with periodical relapses and virus persistence. Gastrointestinal tract (enterocolitis) and respiratory tract (pneumonia) are damaged exhibiting characteristic histological lesions. The monkey model of the CV injection can be used to solve obscure questions of human one.


docid: lqxisawc

title: [Globalization and health].


title: Outbreaks of avian influenza A (H5N1) in Asia and interim recommendations for evaluation and reporting of suspected cases--United States, 2004.

text: During December 2003-February 2004, outbreaks of highly pathogenic avian influenza A (H5N1) among poultry were reported in Cambodia, China, Indonesia, Japan, Laos, South Korea, Thailand, and Vietnam. As of February 9, 2004, a total of 23 cases of laboratory-confirmed influenza A (H5N1) virus infections in humans, resulting in 18 deaths, had been reported in Thailand and Vietnam. In addition, approximately 100 suspected cases in humans are under investigation by national health authorities in Thailand and Vietnam. CDC, the World Health Organization (WHO), and national health authorities in Asian countries are working to assess and monitor the situation, provide epidemiologic and laboratory support, and assist with control efforts. This report summarizes information about the human infections and avian outbreaks in Asia and provides recommendations to guide influenza A (H5N1) surveillance, diagnosis, and testing in the United States.


title: Vasculitis and systemic infections.

text: PURPOSE OF REVIEW In recent years, many investigators have focused on potential associations between infections and vascular inflammation. We review the principal pathogenic mechanisms that have been implicated for possible roles in the vascular inflammation initiated by infectious agents. We also summarize the most important literature related to this topic. RECENT FINDINGS A novel theory known as autoantigen complementarity suggests that an infectious agent could trigger antineutrophil cytoplasmic antibody-associated vasculitis. Several recent studies investigating the presence of parvovirus B19 and herpesviruses in temporal arteries with giant cell arteritis have yielded contradictory results. A recent study has identified higher frequency of a novel human virus, the 'New Haven coronavirus', in respiratory secretions of children with Kawasaki disease. Many case reports have suggested potential relationships between human pathogens and vasculitis. SUMMARY There remains considerable interest in the possibilities of primary vasculitic syndromes caused in some fashion by infection. With the exception of a few well sustained associations - for example hepatitis B or C with known vasculitic syndromes - most of the purported links between microbial agents and primary vasculitides remain speculative.


title: Evidence for immunisation failure in vaccinated adult dogs infected with canine parvovirus type 2c.

text: An outbreak of canine parvovirus type 2c (CPV-2c) infection in vaccinated adult dogs is reported. The disease occurred in a breeding kennel in Italy and affected 11 dogs aged between 6 months and 2.5 years, that had been repeatedly administered vaccines containing a type 2 (old type) CPV strain. CPV infection was demonstrated in all diseased dogs by an immunochromatographic test. A CPV strain was isolated from the intestinal content of a 20-month-old pregnant Bernese mountain bitch that underwent a fatal outcome. The strain was characterised as CPV-2c by means of real-time PCR assays using minor groove binder probes. The present report provides further concerns about the real efficacy of type 2-based vaccines against the antigenic variants of CPV and stresses the need for developing new vaccines prepared with the variants currently circulating in the dog population.


title: Pradimicin A, a carbohydrate-binding nonpeptidic lead compound for treatment of infections with viruses with highly glycosylated envelopes, such as human immunodeficiency virus.

text: Pradimicin A (PRM-A), an antifungal nonpeptidic benzonaphtacenequinone antibiotic, is a low-molecular-weight (molecular weight, 838) carbohydrate binding agent (CBA) endowed with a selective inhibitory activity against human immunodeficiency virus (HIV). It invariably inhibits representative virus strains of a variety of HIV-1 clades with X4 and R5 tropisms at nontoxic concentrations. Time-of-addition studies revealed that PRM-A acts as a true virus entry inhibitor. PRM-A specifically interacts with HIV-1 gp120 and efficiently prevents virus transmission in cocultures of HUT-78/HIV-1 and Sup T1 cells. Upon prolonged exposure of HIV-1-infected CEM cell cultures, PRM-A drug pressure selects for mutant HIV-1 strains containing N-glycosylation site deletions in gp120 but not gp41. A relatively long exposure time to PRM-A is required before drug-resistant virus strains emerge. PRM-A has a high genetic barrier, since more than five N-glycosylation site deletions in gp120 are required to afford moderate drug resistance. Such mutated virus strains keep full sensitivity to the other known clinically used anti-HIV drugs. PRM-A represents the first prototype compound of a nonpeptidic CBA lead and, together with peptide-based lectins, belongs to a conceptually novel type of potential therapeutics for which drug pressure results in the selection of glycan deletions in the HIV gp120 envelope.


docid: lglwfknk

title: Translation and processing of MHV-A59 virion RNA in reticulocyte lysates and infected cells.


title: Porcine teschovirus polioencephalomyelitis in western Canada.

text: Beginning in 2002, a small number of pig farms in western Canada began reporting 4-7-week-old pigs with bilateral hind-end paresis or paralysis. Low numbers of pigs were affected, some died, most had to be euthanized, and those that survived had reduced weight gains and neurological deficits. Necropsies revealed no gross lesions, but microscopic lesions consisted of a nonsuppurative polioencephalomyelitis, most severe in the brain stem and spinal cord. The lesions were most consistent with a viral infection. Tests for circovirus, Porcine reproductive and respiratory syndrome virus, coronavirus, Rabies virus, and Pseudorabies virus were negative. Using immunohistochemistry, virus neutralization, fluorescent antibody test, and nested reverse transcription polymerase chain reaction, Porcine teschovirus was identified in tissues from affected individuals. To the authors' knowledge, this is the first report of teschovirus encephalitis in western Canada and the first reported case of polioencephalomyelitis in pigs in Canada, where teschovirus was confirmed as the cause.


title: The aetiology of community-acquired pneumonia and implications for patient management.

text: PURPOSE Understanding which pathogens are associated with clinical manifestation of community-acquired pneumonia (CAP) is important to optimise treatment. We performed a study on the aetiology of CAP and assessed possible implications for patient management in the Netherlands. METHODS Patients with CAP attending the emergency department of a general hospital were invited to participate in the study. We used an extensive combination of microbiological techniques to determine recent infection with respiratory pathogens. Furthermore, we collected data on clinical parameters and potential risk factors. RESULTS From November 2007 through January 2010, 339 patients were included. Single bacterial infection was found in 39% of these patients, single viral infection in 12%, and mixed bacterial-viral infection in 11%. Streptococcus pneumoniae was the most frequently identified pathogen (22%; n=74). Infection with atypical bacteria was detected in 69 (20%) of the patients. CONCLUSION Initial empirical antibiotics should be effective against S. pneumoniae, the most common pathogen identified in CAP patients. The large proportion of patients with infection with atypical bacteria points to the need for improved diagnostic algorithms including atypical bacteria, especially since these atypical bacteria are not covered by the first-choice antibiotic treatment according to the recently revised Dutch guidelines on the management of CAP.


The way forward: the International Primary Care Respiratory Group 2nd World Conference, Melbourne, 19-22 February 2004.


title: Carbohydrate-binding agents cause deletions of highly conserved glycosylation sites in HIV GP120: a new therapeutic concept to hit the achilles heel of HIV.

text: Mannose-binding proteins derived from several plants (i.e. Hippeastrum hybrid and Galanthus nivalis agglutinin) or prokaryotes (i.e. cyanovirin-N) inhibit human immunodeficiency virus (HIV) replication and select for drug-resistant viruses that show profound deletion of N-glycosylation sites in the GP120 envelope (Balzarini, J., Van Laethem, K., Hatse, S., Vermeire, K., De Clercq, E., Peumans, W., Van Damme, E., Vandamme, A.-M., Bolmstedt, A., and Schols, D. (2004) J. Virol. 78, 10617-10627; Balzarini, J., Van Laethem, K., Hatse, S., Froeyen, M., Van Damme, E., Bolmstedt, A., Peumans, W., De Clercq, E., and Schols, D. (2005) Mol. Pharmacol. 67, 1556-1565). Here we demonstrated that the N-acetylglucosamine-binding protein from Urtica dioica (UDA) prevents HIV entry and eventually selects for viruses in which conserved N-glycosylation sites in GP120 were deleted. In contrast to the mannose-binding proteins, which have a 50-100-fold decreased antiviral activity against the UDA-exposed mutant viruses, UDA has decreased anti-HIV activity to a very limited extent, even against those mutant virus strains that lack at least 9 of 22 ( approximately 40%) glycosylation sites in their GP120 envelope. Therefore, UDA represents the prototype of a new conceptual class of carbohydrate-binding agents with an unusually specific and targeted drug resistance profile. It forces HIV to escape drug pressure by deleting the indispensable glycans on its GP120, thereby obligatorily exposing previously hidden immunogenic epitopes on its envelope.


The 2nd World Veterinary Association-World Medical Association Global Conference on One Health.


title: Development of prehospital, population-based triage-management protocols for pandemics.

text: The lack of disease-specific triage-management protocols that address the unique aspects of a pandemic places emergency medical services, and specifically, emergency medical services practitioners, at great risk. Without adequate protocols, the emergency health system will risk needless exposure, loss of functional capacity, and inappropriately triaged patients. This paper reports on the development of population-based triage-management protocols at two patient points of contact. The primary objective of the triage-management protocols is to identify patients infected by or exposed to the biological agent, and consequently, appropriately triage patients so as to optimize the utilization of emergency medical services and surge capacity resources through disposition and care at hospital- and non-hospital-based care facilities. Protocols must include standardized "flu questions" and a Fear and Resiliency Checklist to ensure protection and separation of the susceptible population from those infected or exposed.