title: Reduced hospitalizations for acute myocardial infarction after implementation of a smoke-free ordinance--City of Pueblo, Colorado, 2002-2006.

text: Exposure to secondhand smoke (SHS) has immediate adverse cardiovascular effects, and prolonged exposure can cause coronary heart disease. Nine studies have reported that laws making indoor workplaces and public places smoke-free were associated with rapid, sizeable reductions in hospitalizations for acute myocardial infarction (AMI). However, most studies examined hospitalizations for 1 year or less after laws were implemented; thus, whether the observed effect was sustained over time was unknown. The Pueblo Heart Study examined the impact of a municipal smoke-free ordinance in the city of Pueblo, Colorado, that took effect on July 1, 2003. The rate of AMI hospitalizations for city residents decreased 27%, from 257 per 100,000 person-years during the 18 months before the ordinance's implementation to 187 during the 18 months after it (the Phase I post-implementation period). This report extends that analysis for an additional 18 months through June 30, 2006 (the Phase II post-implementation period). The rate of AMI hospitalizations among city residents continued to decrease to 152 per 100,000 person-years, a decline of 19% and 41% from the Phase I post-implementation and pre-implementation period, respectively. No significant changes were observed in two comparison areas. These findings suggest that smoke-free policies can result in reductions in AMI hospitalizations that are sustained over a 3-year period and that these policies are important in preventing morbidity and mortality associated with heart disease. This effect likely is mediated through reduced SHS exposure among nonsmokers and reduced smoking, with the former making the larger contribution.


title: Vascular access site influences circuit life in continuous renal replacement therapy.

text: OBJECTIVE To determine the influence of vascular access site on continuous renal replacement therapy (CRRT) filter survival. DESIGN, SETTING AND PATIENTS Retrospective study of the records of patients who received CRRT in The Alfred intensive care unit from June 2011 to May 2012. MAIN OUTCOME MEASURE Filter run time. METHODS We matched filter run time to site and type of vascular access. Mean run times were compared using a linear mixed-effects model between: temporary femoral, internal jugular (IJ) and subclavian catheters, tunnelled semipermanent IJ catheters, and extracorporeal membrane oxygenation (ECMO) circuit access. The Markov chain Monte Carlo method was used to construct 95% confidence intervals, and the Wilcoxon rank sum test was used for post hoc testing of significance. RESULTS Filter run-time data were available for 131 patients (191 occasions of vascular access) with a total of 870 individual filters analysed. Mean run times were subclavian, 14.4 h; IJ, 17.1 h; femoral, 20.2 h; tunnelled IJ, 25.2 h; and ECMO, 29.0 h. Differences were significant for all combinations except between subclavian and IJ, and between tunnelled access and ECMO. Sites in order of best performing to worst-performing were ECMO circuit, tunnelled IJ, femoral vein, direct IJ vein, and subclavian vein. CONCLUSION Vascular access for CRRT plays a significant role in determining filter life. Our study suggests that for temporary dialysis catheters the femoral site should be favoured in ICU patients, and if CRRT is likely to continue for an extended period, a tunnelled IJ line should be considered.


Dialysis and transplantation.


title: [Re-survey on epidemiological history of 1 091 probable cases with severe acute respiratory syndrome in Beijing].

text: OBJECTIVE To know their real epidemiological histories in 1,091 probale cases of severe acute respiratory syndrome (SARS) without definite history of contact with SARS patients in the first survey. METHODS All the probable SARS cases until June 9, 2003 without definite history of contact with SARS patients in the first epidemiological survey were included in a re-survey with questionnaire. The second survey was carried out during June 9 to 30, 2003. RESULTS The results showed that history of contact with other SARS patients was obtained in 15.9% of 1 091 probale SRAS cases in the second survey, transmission of SARS to others was found in 10.5% of them, and source of infection in hospital was found in 46.5%. Comprehensive judgement based on epidemiological history showed that probale history of contact with SARS patients could be found in 72.9% of 1,091 probale cases of SARS in the second survey. CONCLUSION Source of infection could be found through additional survey in part of probale cases of SARS without it in initial epidemiological survey.


title: [Analysis on the epidemiological features and the transmission of an imported severe acute respiratory syndrome case in Beijing].

text: OBJECTIVE To explore the characteristics of severe acute respiratory syndrome (SARS) transmission in the population base on analyzing the first imported case and the chains of transmission. METHODS For the first imported SARS case and cases who were transmitted by the index case, epidemiological investigations were conducted using the guidelines for surveillance and case investigation issued by the Ministry of Health. Data as the date of onset of symptoms, date of hospitalization, contact history etc. for each of the cases and their close contacts were collected and analyzed. RESULTS The first imported SARS case introduced to Beijing had infected 9 people within the family and at the hospital, with two of whom died of the same disease. The incubation period for that index case was 4 days, and that for the cases considered to be the secondary and tertiary generations were 7 and 8 days, respectively. The shorter the incubation period, the longer the fever would last and clinically more severe. CONCLUSION One of the epidemiological characteristics of SARS in Beijing was noticed that the disease clustered in families and hospitals. Infection through droplets and close contact has been viewed as the primary mode of transmission.


Analysis of the functions of coronavirus glycoproteins by differential inhibition of synthesis with tunicamycin.


Acute pharyngitis: etiology and diagnosis.


Molecular ophthalmology: an update on animal models for retinal degenerations and dystrophies.


title: [Development of the integrated TCM hepatology with western medicine].

text: The treatment for severe acute respiratory syndrome (SARS) that happened epidemically this spring confirmed again that the integrated traditional Chinese and western medicine had its clinical advantage and vitality, and indicated that this integration could benefit the pathologic understanding and therapeutic strategies for the diseases. Based on the experimental research, western medicine focuses on the histological and structural changes of the diseases. In order to probe the key mechanisms of the disease's occurrence and development, it tries to develop the therapy targeting the mechanism. Materialism is the academic characteristic of western medicine. Based on the differentiation of individual patient and comprehensive analysis of all manifestations, with the academic characteristic of dynamics and dialectics, traditional Chinese medicine (TCM) focuses on the regulation and recovery of the body functions. Theoretically, materialism and dialectics are complementary to each other. Their combination and unity is the key point for the integration of TCM with western medicine in order to improve the clinical effectiveness and TCM development. Therefore, we must adhere to the principles of the evidence-based medicine, strengthen the integrated study on "disease" of western medicine and "syndrome" of TCM, insist on "materialism" and improve the understanding of the mechanism of Chinese herb formula, pay efforts on the clinical study of difficult and common hepatic diseases, in order to develop the integrated traditional and western medicine on liver diseases.


United States prepares for another flu pandemic.


Coronavirus-associated diarrhea (winter dysentery) in adult cattle.


title: A potential role for tumour necrosis factor-alpha in synergy between porcine respiratory coronavirus and bacterial lipopolysaccharide in the induction of respiratory disease in pigs.

text: This study examined whether exposure of pigs to both porcine respiratory coronavirus (PRCV) and bacterial lipopolysaccharide (LPS) can potentiate respiratory disease and lung secretion of tumour necrosis factor-a (TNF-alpha) and interleukin-1 (IL-1). Caesarian-derived colostrum-deprived pigs were inoculated intratracheally with PRCV, with LPS from Escherichia coli O111:B4 (20 microg/kg), or with a combination of the two, and killed at set times after inoculation. Clinical signs, virus replication and (histo)pathological changes in the lungs, percentage of neutrophils and bioactive TNF-alpha and IL-1 in broncho-alveolar lavage (BAL) fluids were examined. The effects of separate virus or LPS inoculations were subclinical and failed to induce high and sustained cytokine levels. In a preliminary study, pigs were inoculated with PRCV and then with LPS 24 h later and killed sequentially. Severe respiratory disease and significantly enhanced TNF-alpha titres (208-3601 U/ml versus 40-89 U/ml after LPS only) were seen during the first 12 h after LPS inoculation. IL-1 levels (106-1631 U/ml versus 28-654 U/ml after LPS only) were also increased, but persisted for longer after clinical recovery than TNF-alpha. In a second study, pigs were inoculated with PRCV and subsequently with LPS at various time intervals ranging from 0 to 24 h, and killed 5 h after inoculation with LPS. A time interval of at least 12 h between inoculations was necessary for prominent respiratory signs to develop. Production of TNF-alpha, but not IL-1, was also dependent on the time interval between inoculations and was tightly correlated with disease. Lung neutrophil infiltration and pathological changes were comparable after combined PRCV-LPS and single LPS inoculations, and were not associated with disease. These data show that exposure to high endotoxin concentrations in swine buildings can precipitate respiratory disease in PRCV-infected pigs, and that TNF-alpha is probably an important mediator of these effects. This is the first in-vivo demonstration of synergy between respiratory viruses and LPS.


title: [A Case of Gastric Schwannoma Diagnosed Preoperatively].

text: The patient was a 52-year-old woman, who was found to have an abnormality in the upper gastrointestinal(UGI)tract, via a contrast-imaging study; she had no symptoms.Computed tomography(CT)revealed a tumor, measuring approximately 100mm in diameter, in the antrum of the stomach.The tumor was diagnosed as gastric schwannoma using endoscopic ultrasonography-guided fine-needle aspiration(EUS-FNA).Preoperative CT revealed multiple lymph adenopathies around the antrum, which led to the suspicion of lymph node metastasis. The patient underwent a laparoscopic partial gastrectomy after the confirmation of the absence of lymph node metastasis by intraoperative rapid diagnosis.


title: Hydroxychloroquine for COVID-19: What is our Current State of Knowledge?

text: Chloroquine and Hydroxychloroquine are drugs which have been widely used in malaria and rheumatoid arthritis respectively for over 50 years. There was anecdotal evidence of their efficacy in the earlier SARS outbreak in 2003. This prompted physicians from across the world to use them in the present SARS-CoV- 2 pandemic that is currently sweeping the globe, with 5 million people already infected to date. These drugs are already in widespread use for the treatment of COVID-19 in India, mainly because they are cheap and easily available, and because of the absence of any readily available alternative therapy. This timely review discusses the pre-clinical evidence, and data from the eight available clinical trials. We emphasise that careful monitoring for cardiac toxicity is required when these drugs are used. Finally, we conclude that current data does not allow us to recommend for or against the use of these drugs. Results of two large RCTs, one from the NIH and the other from WHO (Solidarity) are eagerly awaited before the role of these drugs in COVID-19 can be definitively established.


title: Herbal medicine research and global health: an ethical analysis.

text: Governments, international agencies and corporations are increasingly investing in traditional herbal medicine research. Yet little literature addresses ethical challenges in this research. In this paper, we apply concepts in a comprehensive ethical framework for clinical research to international traditional herbal medicine research. We examine in detail three key, underappreciated dimensions of the ethical framework in which particularly difficult questions arise for international herbal medicine research: social value, scientific validity and favourable risk-benefit ratio. Significant challenges exist in determining shared concepts of social value, scientific validity and favourable risk-benefit ratio across international research collaborations. However, we argue that collaborative partnership, including democratic deliberation, offers the context and process by which many of the ethical challenges in international herbal medicine research can, and should be, resolved. By "cross-training" investigators, and investing in safety-monitoring infrastructure, the issues identified by this comprehensive framework can promote ethically sound international herbal medicine research that contributes to global health.


title: Complications after transcatheter arterial embolization for pelvic trauma: relationship to level and laterality of embolization.

text: PURPOSE Transcatheter arterial embolization (TAE) is commonly used to control hemorrhage after pelvic trauma. Despite the procedures reported safety, there can be severe complications, mostly related to ischemia of embolized tissues. Our purpose was to examine the complications of trauma patients resulting from the embolization techniques utilized at our level 1 trauma center. MATERIALS AND METHODS A retrospective chart review was conducted. One hundred and seven patients who underwent pelvic embolization between January 2003 and December 2013 were included. Patient demographics, ISS, angiography techniques, and major complications including gluteal and skin necrosis, wound breakdown, and deep infection were compared. RESULTS Nine patients (8.4 %) developed major complications after undergoing TAE. This rate dropped to 5.1 % after exclusion of patients with Morel-Lavallee lesions. Nonselective embolization trended toward a higher complication rate compared to superselective embolization. Patients who developed complications were more likely to have undergone pelvic surgery. CONCLUSION The majority of patients who developed complications had nonselective TAE. Morel-Lavallee lesions are a confounding factor, but TAE may impose an additional risk. Pelvic surgery after TAE may further predispose patients to complications. We recommend superselective embolization as first-line treatment and caution the use of prophylactic embolization, especially in patients with substantial pelvic soft tissue injuries.


title: Nutritional aspects of HIV-infected children receiving highly active antiretroviral therapy.

text: The presentation of the nutritional problems of HIV-infected children is changing over time with improved antiretroviral regimens. Early reports of HIV infection in the 1980s, included such problems as malnutrition and wasting. However, as treatment and prophylactic regimens improve, the current nutritional problems of HIV-infected children in developed countries include truncal obesity and insulin resistance in addition to malnutrition. Background data on the wasting syndrome, etiology of malnutrition, nutritional effects of highly active antiretroviral therapies, and nutritional intervention strategies for HIV-infected children will be presented.


title: The origins of cognitive dissonance: evidence from children and monkeys.

text: In a study exploring the origins of cognitive dissonance, preschoolers and capuchins were given a choice between two equally preferred alternatives (two different stickers and two differently colored M&M's, respectively). On the basis of previous research with adults, this choice was thought to cause dissonance because it conflicted with subjects' belief that the two options were equally valuable. We therefore expected subjects to change their attitude toward the unchosen alternative, deeming it less valuable. We then presented subjects with a choice between the unchosen option and an option that was originally as attractive as both options in the first choice. Both groups preferred the novel over the unchosen option in this experimental condition, but not in a control condition in which they did not take part in the first decision. These results provide the first evidence of decision rationalization in children and nonhuman primates. They suggest that the mechanisms underlying cognitive-dissonance reduction in human adults may have originated both developmentally and evolutionarily earlier than previously thought.


title: Hypercytokinemia and hyperactivation of phospho-p38 mitogen-activated protein kinase in severe human influenza A virus infection.

text: BACKGROUND We postulate that hypercytokinemia plays a role in immunopathogenesis of severe human influenza. METHODS We prospectively studied 39 consecutive patients who were hospitalized with severe influenza A virus infection. On laboratory confirmation of the diagnosis, paired acute-phase (obtained at hospital admission) and convalescent-phase (obtained >10 days after hospital admission) plasma samples were collected for assay of 11 cytokines and chemokines (interleukin [IL] 1 beta; IL-6; IL-10; IL-12p70; tumor necrosis factor alpha; IL-8; monokine induced by interferon [IFN]-gamma; IFN-inducible protein 10; monocyte chemoattractant protein 1; regulated upon activation, normal T cell-expressed and secreted; and IFN-gamma) using cytometric bead-array analysis and enzyme-linked immunosorbent assay. Simultaneously, virus concentration in the acute-phase nasopharyngeal aspirate was determined using real-time quantitative reverse-transcriptase polymerase chain reaction. Intracellular signaling molecules regulating lymphocyte activation, phospho-p38 mitogen-activated protein kinase and phospho-extracellular signal-regulated protein kinase in CD4+ and CD8+ T lymphocytes were studied in the acute-phase samples using flow cytometric analysis and were compared with results for samples from healthy control subjects. RESULTS Statistically significant increases in plasma IL-6 (3.7-fold increase), IL-8 (2.6-fold increase), IFN-induced protein 10 (4.9-fold increase), and monokine induced by IFN-gamma (2.3-fold increase) concentrations were detected during acute illness (P < .01 for all, by Wilcoxon signed-rank test); the highest concentrations were observed on symptom days 3 and 4. Corresponding plasma cytokine and chemokine concentrations and nasopharyngeal viral loads showed statistically significant correlations (rho = 0.41, 0.49, 0.54, and 0.46, respectively; P < or = .01). Phospho-p38 mitogen-activated protein kinase expression in CD4+ lymphocytes was increased, correlating with cytokine concentrations (e.g., for IFN-induced protein 10, rho = 0.78; P < .01); phospho-extracellular signal-regulated protein kinase was suppressed. Advanced age and comorbidity were associated with aberrant IL-6, IL-8, and monokine induced by IFN-gamma responses (P < .05, by Mann-Whitney U test). An elevated IL-6 concentration was independently associated with prolonged hospitalization (hospitalization for >5 days; P = .02), adjusted for age, comorbidity, and virus load. CONCLUSIONS Hypercytokinemia (of proinflammatory and T helper 1 cytokines) is detected in severe influenza, correlating with clinical illness and virus concentration. Hyperactivation of phospho-p38 mitogen-activated protein kinase (in T helper cells) is possibly involved. Early viral suppression may attenuate these potentially deleterious cytokine responses.


title: Epidemiology and food safety.

text: With the introduction of the Food Safety Initiative in 1997, food safety activities and research funding have increased dramatically. Advances in microbiological methods and epidemiologic research have provided significant progress in our understanding of foodborne diseases and in our implementation of control programs. This article highlights some of those food safety activities and epidemiologic research programs. This article also describes potential future research areas and activities.


title: Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment?

text: BACKGROUND Studies from the Spanish influenza era reported that transfusion of influenza-convalescent human blood products reduced mortality in patients with influenza complicated by pneumonia. Treatments for H5N1 influenza are unsatisfactory, and convalescent human plasma containing H5N1 antibodies could be an effective therapy during outbreaks and pandemics. PURPOSE To determine whether transfusion with influenza-convalescent human blood products reduced the risk for death in patients with Spanish influenza pneumonia. DATA SOURCES Manual search of English-language journals from 1918 to 1925. Citations from retrieved studies were also searched. STUDY SELECTION Published English-language studies that had at least 10 patients in the treatment group, used convalescent blood products to treat Spanish influenza pneumonia in a hospital setting, and reported on a control or comparison group. DATA EXTRACTION Two investigators independently extracted data on study characteristics, outcomes, adverse events, and quality. DATA SYNTHESIS Eight relevant studies involving 1703 patients were found. Treated patients, who were often selected because of more severe illness, were compared with untreated controls with influenza pneumonia in the same hospital or ward. The overall crude case-fatality rate was 16% (54 of 336) among treated patients and 37% (452 of 1219) among controls. The range of absolute risk differences in mortality between the treatment and control groups was 8% to 26% (pooled risk difference, 21% [95% CI, 15% to 27%]). The overall crude case-fatality rate was 19% (28 of 148) among patients who received early treatment (after <4 days of pneumonia complications) and 59% (49 of 83) among patients who received late treatment (after > or =4 days of pneumonia complications). The range of absolute risk differences in mortality between the early treatment group and the late treatment group was 26% to 50% (pooled risk difference, 41% [CI, 29% to 54%]). Adverse effects included chill reactions and possible exacerbations of symptoms in a few patients. LIMITATIONS Studies were few and had many methodologic limitations. No study was a blinded, randomized, or placebo-controlled trial. Some pertinent studies may have been missed. CONCLUSIONS Patients with Spanish influenza pneumonia who received influenza-convalescent human blood products may have experienced a clinically important reduction in the risk for death. Convalescent human H5N1 plasma could be an effective, timely, and widely available treatment that should be studied in clinical trials.


title: Enzyme-linked immunosorbent assay for detection of antibody in volunteers experimentally infected with human coronavirus strain 229 E.

text: An enzyme-linked immunosorbent assay was developed for detecting antibody rises to human coronavirus strain 229E and related strains in paired sera from infected volunteers. There was a close correlation between development of colds infected volunteers. There was a close correlation between development of colds and significant antibody rises detected by the enzyme-linked immunosorbent assay. Furthermore, the assay was more sensitive than a neutralization assay. This enzyme-linked immunosorbent assay is an easy, accurate, and sensitive assay for measuring significant antibody rises to human coronavirus strain 229E group viruses, and it could be useful in the clinical diagnosis of these infections.


Barrett Esophagus: Prevalence, Treatment, and the Link to Esophageal Adenocarcinoma.


title: A 3D model of SARS_CoV 3CL proteinase and its inhibitors design by virtual screening.

text: AIM To constructed a three-dimensional (3D) model for the 3C like (3CL) proteinase of SARS coronavirus (SARS-CoV), and to design inhibitors of the 3CL proteinase based on the 3D model. METHODS Bioinformatics analyses were performed to search the homologous proteins of the SARS-CoV 3CL proteinase from the GenBank and PDB database. A 3D model of the proteinase was constructed by using homology modeling technique. Targeting to the 3D model and its X-ray crystal structure of the main proteinase (Mpro) of transmissible gastroenteritis virus (TGEV), virtual screening was performed employing molecular docking method to identify possible 3CL proteinase inhibitors from small molecular databases. RESULTS Sequence alignment indicated that the SARS-CoV 3CL proteinase was extremely homologous to TGEV Mpro, especially the substrate-binding pocket (active site). Accordingly, a 3D model for the SARS-CoV 3CL proteinase was constructed based on the crystal structure of TGEV Mpro. The 3D model adopts a similar fold of the TGEV Mpro, its structure and binding pocket feature are almost as same as that of TGEV Mpro. The tested virtual screening indicated that 73 available proteinase inhibitors in the MDDR database might dock into both the binding pockets of the TGEV Mpro and the SARS-CoV 3CL proteinase. CONCLUSIONS Either the 3D model of the SARS-CoV 3CL proteinase or the X-ray crystal structure of the TGEV Mpro may be used as a starting point for design anti-SARS drugs. Screening the known proteinase inhibitors may be an appreciated shortcut to discover anti-SARS drugs.


title: The public health system in Canada: not meeting the needs of Canadians.

text: Public health renewal, given increased momentum in Canada by our experience with severe acute respiratory syndrome (SARS) and the subsequent "Naylor Report" (National Advisory Committee on SARS and Public Health 2003), has undergone some similar and some very different challenges compared with the United States. Canada's publicly funded healthcare system and large and sparse geography provide some challenges other than those highlighted by Tilson and Berkowitz.


title: A structural determinant of human cytomegalovirus US2 dictates the down-regulation of class I major histocompatibility molecules.

text: Human cytomegalovirus down-regulates cell surface class I major histocompatibility (MHC) molecules, thus allowing the virus to proliferate while avoiding detection by CD8+ T lymphocytes. The unique short gene product US2 is a 199-amino acid type I endoplasmic reticulum glycoprotein that modulates surface expression of class I MHC products by targeting class I heavy chains for dislocation from the endoplasmic reticulum to the cytosol, where they undergo proteasomal degradation. Although the mechanism by which this viral protein targets class I heavy chains for destruction remains unclear, the putative US2 cytoplasmic tail comprised of only 14 residues is known to play a functional role. To determine the specific residues critical for mediating class I degradation, a mutagenesis analysis of the cytoplasmic tail of US2 was performed. Using truncation mutants, the removal of only 4 residues (mutant US2(195)) from the US2 carboxyl terminus completely abolishes class I destruction. Furthermore, site-directed mutagenesis of the US2 cytoplasmic tail revealed that the most critical residues for class I-induced destruction, cysteine 187, serine 190, tryptophan 193, and phenylalanine 196, occurs every third residue. This experimental data supports a model that the US2 cytoplasmic tail is in a 3(10) helical configuration. Such a secondary structure would predict that one side of the 3(10) helical cytoplasmic tail would interact with the extraction apparatus to facilitate the dislocation and subsequent destruction of class I heavy chains.


title: Use of RT-PCR for diagnosis of infectious salmon anaemia virus (ISAV) in carrier sea trout Salmo trutta after experimental infection.

text: The emergence of infectious salmon anaemia virus (ISAV) in Canada and Scotland and frequent new outbreaks of the disease in Norway strongly suggest that there are natural reservoirs for the virus. The main host for the ISA virus is probably a fish occurring in the coastal area, most likely a salmonid fish. Since sea trout is an abundant species along the Norwegian coast, common in areas where ISA outbreaks occur, and possibly a life-long carrier of the ISA virus, a study was initiated to evaluate reverse transcriptase polymerase chain reaction (RT-PCR) for diagnosis of the virus in experimentally infected trout. Several tissues (kidney, spleen, heart and skin) were collected from the trout during a 135 d period. The following diagnostic methods for detection of the ISA virus were compared: cell culture (Atlantic Salmon Kidney, ASK cells), challenge of disease-free salmon with blood from the infected trout, and RT-PCR. The RT-PCR was the most sensitive of these methods. With the help of this technique it was possible to pick out positive individuals throughout the experimental period of 135 d. Challenge of disease-free salmon were more sensitive than cell culture (ASK cells). These 2 latter methods require use of the immunofluorescent antibody test (IFAT) or RT-PCR for verification of presence of ISA virus.


Severe acute respiratory syndrome and influenza: virus incursions from southern China.


title: Evaluation of a prototype sub-unit vaccine against equine arteritis virus comprising the entire ectodomain of the virus large envelope glycoprotein (G(L)): induction of virus-neutralizing antibody and assessment of protection in ponies.

text: An Escherichia coli-expressed recombinant protein (6hisG(L)ecto) comprising the entire ectodomain (aa 18-122) of equine arteritis virus (EAV) glycoprotein G(L), the immunodominant viral antigen, induced higher neutralizing antibody titres than other G(L)-derived polypeptides when compared in an immunization study in ponies. The potential of the recombinant G(L) ectodomain to act as a sub-unit vaccine against EAV was evaluated further in three groups of four ponies vaccinated with doses of 35, 70 or 140 microg of protein. All vaccinated animals developed a virus-neutralizing antibody (VNAb) response with peak titres 1-2 weeks after the administration of a booster on week 5 (VNAb titres of 1.8-3.1), 13 (VNAb titres of 1.4-2.9) or 53 (VNAb titres of 1.2-2.3). Vaccinated and unvaccinated control ponies were infected with EAV at different times post-vaccination to obtain information about the degree of protection relative to the levels of pre-challenge VNAb. Vaccination conferred varying levels of protection, as indicated by reduced or absent pyrexia, viraemia and virus excretion from the nasopharynx. The degree of protection correlated well with the levels of pre-challenge VNAb and, in particular, with levels of virus excretion. These results provide the first evidence that a sub-unit vaccine protects horses against EAV. The use of the sub-unit vaccine in combination with a differential diagnostic test based on other EAV antigens would enable serological discrimination between naturally infected and vaccinated equines.


title: Molecular identification and characterization of novel coronaviruses infecting graylag geese (Anser anser), feral pigeons (Columbia livia) and mallards (Anas platyrhynchos).

text: In light of the finding of a previously unknown coronavirus as the aetiology of the severe acute respiratory syndrome (SARS), it is probable that other coronaviruses, than those recognized to date, are circulating in animal populations. Here, the results of a screening for coronavirus are presented, using a universal coronavirus RT-PCR, of the bird species graylag goose (Anser anser), feral pigeon (Columbia livia) and mallard (Anas platyrhynchos). Coronaviruses were found in cloacal swab samples from all the three bird species. In the graylag goose, 40 of 163 sampled birds were coronavirus positive, whereas two of 100 sampled pigeons and one of five sampled mallards tested positive. The infected graylag geese showed lower body weights compared with virus-negative birds, suggesting clinical significance of the infection. Phylogenetic analyses performed on the replicase gene and nucleocapsid protein sequences, indicated that the novel coronaviruses described in the present study all branch off from group III coronaviruses. All the novel avian coronaviruses harboured the conserved s2m RNA structure in their 3' untranslated region, like other previously described group III coronaviruses, and like the SARS coronavirus. Sequencing of the complete nucleocapsid gene and downstream regions of goose and pigeon coronaviruses, evidenced the presence of two additional open reading frames for the goose coronavirus with no sequence similarity to known proteins, but with predicted transmembrane domains for one of the encoded proteins, and one additional open reading frame for the pigeon coronavirus, with a predicted transmembrane domain, downstream of the nucleocapsid gene.


title: The precision and accuracy of Nellcor and Masimo oximeters at low oxygen saturations (70%) in newborn lambs.

text: BACKGROUND Administration of oxygen in the delivery room is informed by oxygen saturation (SpO₂). An oxygen saturation range of 60%-70% is the threshold for administering oxygen in the first minutes after birth. The accuracy of newer generation oximeters to measure SpO₂ has not been compared against the 'gold standard', direct arterial blood oxygen saturation (SaO₂) when SaO₂ is low. The aim of this study was to determine the accuracy and precision of Nellcor and Masimo oximeters to measure SpO₂ when SaO₂ <70%. METHOD Prospective observational study in ventilated anaesthetised newborn lambs with an indwelling carotid artery catheter. Ventilation was adjusted to achieve hypoxaemia. Nellcor (Oxi-Max 600 with Max-N sensor) and Masimo (Rad 4 with low noise optical probe (LNOP) sensor) sensors were applied to the right forelimb (preductal). An arterial blood sample was collected at 1-5 min intervals when the animal was hypoxic. The displayed SpO₂ was recorded. We used Bland-Altman analysis to determine precision and accuracy of each oximeter when SaO₂ <70%. RESULTS 17 lambs were studied, 165 measurements were obtained, 123 were SaO₂ <70%. The mean difference (±1.96 SD) Nellcor SpO₂-SaO₂ when SaO₂ <70% was 17% (-12% to 46%). The mean difference (±1.96 SD) Masimo SpO₂-SaO₂ when SaO2 <70% was 13% (-19% to 45%). CONCLUSIONS At SaO₂<70%, both monitors overestimated oxygen saturation (SpO₂) compared with the gold standard. Both oximeters were equally inaccurate when SaO₂ was low.


title: [De-escalation urology measures. COVID-19 pandemia stepwise recommendations.]

text: El nuevo coronavirus tipo 2 (SARS-CoV-2)del síndrome respiratorio agudo grave y la enfermedadque produce, enfermedad por coronavirus2019 (COVID-19) fueron descritos por primera vezen la ciudad China de Wuhan en Diciembre de2019 (1). En Marzo de 2020, la dispersión mundialde este nuevo patógeno, condujo a la declaraciónde pandemia por parte de la Organización Mundialde la Salud (OMS) (2).


title: Modulation of acute coronavirus-induced encephalomyelitis in gamma-irradiated rats by transfer of naive lymphocyte subsets before infection.

text: Clinical course, recovery of infectious virus from brain tissue and histopathology of the central nervous system were examined in gamma-irradiated Lewis rats reconstituted by naive lymphocytes before infection with coronavirus MHV-4 (strain JHM). Up to 9 days past infection, no differences were seen between immunologically competent and immuno-deficient animals in terms of onset and progression of neurological disease. However, in the latter animals neurological symptoms were dominated by signs of encephalitis instead of paralytic disease as usually seen in immunocompetent animals. Nevertheless, despite high titers of infectious virus in the CNS of immunodeficient animals only mild histopathological changes were noticeable. In contrast, infectious virus in the CNS of immunologically competent animals was below the detection limit of the assay. Paralytic disease and tissue destruction were T lymphocyte mediated because gamma-irradiated rats that were reconstituted by CD4+ or CD8+ T lymphocyte enriched cells in the absence of B lymphocytes revealed an earlier onset of clinical symptoms and a more rapid deterioration of their clinical state compared to fully competent animals. Whereas in CD4+ T cell reconstituted animals infectious virus was moderately reduced and tissue destruction as well as inflammatory changes in the CNS were focal, in CD8+ T cell reconstituted animals vacuolizing white matter inflammation was diffuse without reduction of infectious virus in brain tissue. From the presented data we conclude that in the acute stage of JHMV-induced encephalomyelitis of Lewis rats: (i) tissue destruction and paralytic clinical symptomatology are mainly T cell-mediated; (ii) CD4+ T lymphocytes can directly contribute to reduction of viral load in the brain and (iii) only coordinated action of both, the T and the B cell compartment enables animals to survive the infection and recover from disease.


Coronavirus: organization, replication and expression of genome.


MERS-CoV: Where Are We Now?


title: Enzymatic degradation study of 111In-labeled minigastrin peptides using cathepsin B enzyme and AR42J cancer cell line for the development of neuroendocrine tumor imaging radiopharmaceuticals.

text: Neuroendocrine tumors (NET) are the rare tumors which often impose graveyard threat. These tumors are characterized by the over expression of various G-protein coupled receptors including cholecystokinin (CCK) receptors-1 and 2 (A or B). Minigastrin peptides are being investigated for theranostic purposes of CCK-2 receptor positive NET. The minigastrin analogue (APHO70) was modified by engineering enzyme susceptible tetrapeptide sequence into APHO70 peptide to reduce the random degradation by lysosome enzymes which pave the way to random trafficking in patient's body and dipeptide addition at c-terminus. All the four modified minigastrin peptides (MG-CL1-4) were investigated for lysosome cathepsin B (catB) enzyme susceptibility and fate into AR42J cancer cell line. The indium-111 labeled MG-CL1-4 peptides were also studied for target (tumor) and non-target saccumulation by using tumor induced mice. The RP-HPLC analysis result showed nonspecific cleavage of standard 111In-APH070 and 111In-MGCL1 while specific cleavage was noted in case of 111In-MGCL (2-4). The effect of specific and non-specific cleavage on biodistribution in tumor induced nude mice model indicates the promising accumulation of 111In-MGCL2, 111In-MGCL3, and 111In-MGCL4 radiotracers while 111In-MGCL1 showed less accumulation. 111In-MGCL2 and 111In-MGCL3 showed highest target-to-kidney ratio (T/K) i.e. 1.71 and 1.72, respectively whereas standard compound showed T/K 1.13. In conclusion, the two indium-111 labeled analogues i.e. 111In-MGCL2 and 111In-MGCL3 showed promising sensitivity for tumor andcould be tested for further investigation to reach pre-clinical studies.


A tradition of caring.


title: Domesticated nature: shaping landscapes and ecosystems for human welfare.

text: Like all species, humans have exercised their impulse to perpetuate and propagate themselves. In doing so, we have domesticated landscapes and ecosystems in ways that enhance our food supplies, reduce exposure to predators and natural dangers, and promote commerce. On average, the net benefits to humankind of domesticated nature have been positive. We have, of course, made mistakes, causing unforeseen changes in ecosystem attributes, while leaving few, if any, truly wild places on Earth. Going into the future, scientists can help humanity to domesticate nature more wisely by quantifying the tradeoffs among ecosystem services, such as how increasing the provision of one service may decrease ecosystem resilience and the provision of other services.


title: Morphologic features and development of granulomatous vasculitis in feline infectious peritonitis.

text: Feline infectious peritonitis (FIP) is a fatal, coronavirus (CoV)-induced systemic disease in cats, characterized by granulomas in organs and granulomatous vasculitis. This study describes the morphologic features of granulomatous vasculitis in FIP as well as its development in the course of monocyte-associated feline CoV (FCoV) viremia in five naturally infected Domestic Shorthair cats with FIP. Monocyte-associated FCoV viremia was demonstrated by immunohistology, RNA in situ hybridization, and electron micropscopy. Granulomatous phlebitis at different stages of development was observed. Vasculitic processes ranged from attachment and emigration of FCoV-infected monocytes to vascular/perivascular granulomatous infiltrates with destruction of the vascular basal lamina. Monocytes as well as perivascular macrophages were activated because they were strongly positive for CD18 and expressed cytokines (tumor necrosis factor-alpha and interleukin-1beta) and matrix metalloproteinase-9. In addition, general activation of endothelial cells, represented by major histocompatibility complex II upregulation, was observed in all cases. These results confirm FIP as a monocyte-triggered systemic disease and demonstrate the central role of activated monocytes in FIP vasculitis.


title: Antigenic studies on coronavirus. I. Identification of the structural antigens of human coronavirus, strain 229E.

text: Antigenic analysis of human coronavirus, strain 229E (HCV/229E), using a microimmunodiffusion technique, has resulted in the detection of six virion antigens. Comparison of the effect of several different virus-disrupting agents has shown that sodium deoxycholate or Triton X-100 were the best for HCV/229E disruption. Of the six coronavirion antigens, three were identified as virus specific and the remainder as host antigens, which were present as either integrated or nonspecifically adsorbed host components. One of the virus-specific antigens was identified as the internal nucleoprotein (229E/RNP). On the basis of immunodiffusion reactions with isolated 229E/RNP it was concluded that human convalescent sera reacted specifically with the 229E/RNP antigen.


title: Heme- and nonheme-iron absorption and iron status 12 mo after sleeve gastrectomy and Roux-en-Y gastric bypass in morbidly obese women.

text: BACKGROUND The effect of bariatric surgery on iron absorption is only partially known. OBJECTIVE The objective was to study the effects of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGBP) on heme- and nonheme-iron absorption and iron status. DESIGN Fifty-eight menstruating women were enrolled in this prospective study [mean (±SD) age: 35.9 ± 9.1 y; weight: 101.7 ± 13.5 kg; BMI (in kg/m²): 39.9 ± 4.4]. Anthropometric, body-composition, dietary, and hematologic indexes and heme- and nonheme-iron absorption-using a standardized meal containing 3 mg Fe-were determined before and 12 mo after surgery. Forty-three subjects completed the 12-mo follow-up. Iron supplements were strictly controlled. RESULTS Heme-iron absorption was 23.9% before and 6.2% 12 mo after surgery (P < 0.0001). Nonheme-iron absorption decreased from 11.1% to 4.7% (P < 0.0001). No differences were observed by type of surgery. Iron intakes from all sources of supplements were 27.9 ± 6.2 mg/d in the SG group and 63.2 ± 21.1 mg/d in the RYGBP group (P < 0.001). Serum ferritin and total-body iron decreased more after RYGBP than after SG. CONCLUSIONS Iron (heme and nonheme) absorption is markedly reduced after SG and RYGBP. The magnitude of the decrease in heme-iron absorption is greater than that of nonheme iron. The amounts suggested as iron supplements may need to be increased to effectively prevent iron-status impairment.


title: Is there a potential application of a fermented nutraceutical in acute respiratory illnesses? An in-vivo placebo-controlled, cross-over clinical study in different age groups of healthy subjects.

text: The role of oxidants in viral diseases is fairly complex because it includes metabolic regulation both of host metabolism and viral replication. However, a role for reactive oxygen species (ROS) and reactive nitrogen species (RNS) as mediators of virus-induced lung damage is supported by studies and antioxidants can thus be expected to act at many different levels. The aim of the present pilot study was to test an antioxidant nutraceutical approach on some relevant immunological parameters known to be affected in common seasonal respiratory tract infection. The study population consisted of 90 sedentary healthy patients, previously selected as being GSTM1-positive, divided into three groups: A) 20-40 years; B) 41-65 years; B) over 65 years. Each patients was administered a life style and dietary questionnaire. Subjects were supplemented for 6 weeks with either 9g/day (4.5g twice a day sublingually) of a fermented papaya preparation (Osato Research Institute, Gifu, Japan) or placebo. After a further month period of wash out, subjects were treated again in a crossover manner. Parameters checked were as follows: routine blood tests with WBC formula, saliva flow rate and secretary IgA and lysozyme production and redox gene expression of Phase II enzyme and SOD from upper airways cells (from nasal lavage). Salivary secretion rate showed an age-related decline and was significantly increased by FPP supplementation only in the youngest age-group (p less than 0.05). Subjects treated with FPP showed a significantly higher lever of IgA and lisozyme production., irrespective of age group while their baseline production was significantly lower in the oldest age-group as compared to the youngest one (C vs A, p less than 0.05). FPP treatment brought about a significant upregulation of all phase II enzyme and SOD gene expression tested in nasal lavage cells. In conclusion, FPP supplementation during 1 month resulted in higher salivary IgA and increase in phase II and SOD enzyme expression, i.e the most important antioxidant in the respiratory tract. The biological significance of these effects i.e., whether it will help reducing the whole respiratory oxidative stress in the human airway and, hopefully, the incidence and/or severity of URTI remains to be demonstrated in longer clinical trials.


title: Diathermy versus scalpel in Limberg flap in pilonidal sinus surgery. A prospective randomized trial.

text: BACKGROUND Rhomboid excision with Limberg flap repair (RELIF) is an effective surgical procedure in pilonidal sinus disease (PSD) treatment. This study aimed to compare outcome of diathermy and scalpel in RELIF procedure in PSD surgery. METHODS Patients undergoing RELIF procedure due to PSD at Adana Numune Training and Research Hospital between January 2012 and September 2012 were randomly assigned to diathermy (n=30) or scalpel (n=30) groups. The primary outcomes measured were duration of operation, drainage volume, postoperative numerical pain intensity scale (NPIS) scores, complications, duration of hospitalization length and time to return to daily activity. RESULTS The mean age was 26.2 years (17-44 years). The mean operation duration was significantly lower in diathermy group (p=0.0001). Postoperative total NPIS score within the first 24 h was significantly lower in diathermy group (p=0.001). However, there were not any significant differences in term of NPIS scores in day 3 and day 7. There were no significant differences in terms of total drain output, drain removal time and length of hospital stay. There were no significant differences between groups in terms of duration to sit comfortably, return to daily activity and work. Recurrence of PSD was emerged in one patient in the diathermy group. CONCLUSION Diathermy dissection in RELIF procedure in pilonidal sinus surgery is a safe technique and decreased operation time and postoperative pain.


title: [Diagnostic efficacy of three test kits for SARS-CoV-2 nucleic acid detection].

text: OBJECTIVE To compare the diagnostic efficacy among three RT-PCR test kits for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid detection. METHODS The throat swab samples from 40 hospitalized patients clinically diagnosed as coronavirus disease 2019 (COVID-19) and 16 hospitalized non-COVID-19 patients were recruited. The SARS-CoV-2 nucleic acid was detected in throat swab samples with RT-PCR test kits from Sansure Biotech ("Sansure" for short), Jiangsu Bioperfectus Technologies ("Bioperfectus" for short) and BGI Genomics ("BGI" for short). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and Kappa value were analyzed. The viral nucleic acid was extracted from the throat swab samples by one-step cleavage and magnetic bead methods, and the efficacy of two extraction methods was also compared. The results of magnetic bead method for nucleic acid extraction by two different extractors (Sansure Natch CS S12C Fully Automated Nucleic Acid Extraction System vs. Tianlong NP968-C Nucleic Acid Extractor) were also compared. RESULTS The sensitivity, specificity, PPV, NPV and kappa value were 95.00%, 87.50%, 95.00%, 87.50%and 0.825 for Sansure kit; 90.00%, 87.50%, 94.74%, 77.78%and 0.747 for the Bioperfectus kit, and 82.50%, 81.25%, 91.67%, 65.00%and 0.593 for the BGI kit, respectively. The positive, negative and total coincident rates and kappa value of viral nucleic acid detection results using the samples extracted by one-step cleavage and magnetic bead methods were 95.24%, 100.00%, 96.43%and 0.909, respectively, but the one-step cleavage method took only 25 min, while the magnetic bead method required 180 min. The positive, negative and total coincident rates and kappa value of viral nucleic acid detection results using the samples extracted by the two different nucleic acid extractors were 85.00%, 100.00%, 89.29% and 0.764, respectively. CONCLUSIONS The detection efficacy for SARS-CoV-2 nucleic acid by the Sansure kit is relatively higher and the one-step cleavage method has advantages of convenient operation and less time consuming.


title: A cluster of Legionella-associated pneumonia cases in a population of military recruits.

text: A Legionella cluster was identified through retrospective PCR analysis of 240 throat swab samples from X-ray-confirmed pneumonia cases. These were identified among young and otherwise healthy U.S. military recruits during population-based surveillance for pneumonia pathogens. Results were confirmed by sequence analysis. Cases clustered tightly, suggesting a local environmental etiology.


title: [Persistence of the Sindbis virus in cultures producing oncornavirus].

text: Continuous lines were obtained from primary cultures of BALB/C mouse embryo cells which were found by electron microscope and reverse transcriptase reaction to produce permanently oncoronavirus type C after exogenous infection with Rauscher leukemia virus (RLV). Sindbis virus (SV) was inoculated into virogenic cultures 398 days after infection with RLV. The system in characterized by rapid (3-21 days) disappearance of the infectious arbovirus from the medium and the cells, long-term (over 5 months) persistence on SV noninfectious antigen and signs of stimulation of oncornavirus activity. The level of reverse transcriptase activity in cultures in the presence of persisting arbovirus was 1.5-3.3-fold higher than in cultures infected with RLV alone. Two variants of the course of mixed chronic infection of the cultures with oncornavirus and arbovirus differing in the rate of transition of the arbovirus into the noninfectious form and inhibition or stimulation of oncornavirus functions are discussed.


title: Viral infections.

text: This article has concentrated on the etiology, pathogenesis, diagnosis, and treatment of viral infections of the hand. Some of these entities are quite common, but are often misdiagnosed. Herpes simplex appears to be the most common viral infection involving the hand. These and other viral infections can have much graver consequences in immunosuppressed patients. Recurrent episodes are common in herpetic and other viral infections. Health care workers have long been at risk, but improved compliance with prophylactic measures would seem to be decreasing the number of cases in this population. A plea has been made to disregard the term herpetic whitlow because it is an inaccurate description of the lesion and implies that an inappropriate type of treatment is required. Bacterial whitlows or felons require incision and drainage of the deep pulp space. Herpetic infections in this area do not. Less common infections such as cowpox, pseudocowpox (milkers nodules), ORF, and coxsackievirus (HFMD) infection of the hand have been brought to the attention of the reader. The bothersome warts caused by the human papillomavirus have been described and the systemic ramifications of hand-to-hand contact and hand injury causing more serious viral problems has been mentioned. A common thread in the care of the patient with these types of diseases is that an adequate history and physical remain invaluable in arriving at the correct diagnosis. With this correct diagnosis all of us, as physicians, then can easily abide by one of our basic principles Primum non nocere, "Let me help--but first let me do no harm."


title: Cellular autophagy machinery is not required for vaccinia virus replication and maturation.

text: The origin of the primary membrane of the vaccinia virus, a double-membrane structure that surrounds the immature virions (IV), is not fully understood. Here we investigated whether the primary membrane originates from the autophagic membrane. Morphologic studies by electron microscopy (EM) showed no apparent difference in viral maturation in the autophagy-deficient cell lines, the atg5(-/-) mouse embryonic fibroblasts (MEFs) and the beclin1(-/-) embryonic stem (ES) cells, compared to their isogenic wild-type counterparts. Moreover, viral growth curves demonstrated that vaccinia viruses replicate and mature in the autophagy-deficient cell lines as efficiently as they do in their isogenic wild type counterpart cells. This study indicates that the cellular autophagy machinery is not required for the life-cycle of vaccinia virus, suggesting that the primary vaccinia viral membrane does not originate from the autophagic membrane.


title: Virologic and immunologic aspects of feline infectious peritonitis virus infection.

text: A number of feline coronavirus isolates have been characterized over the last few years. These isolates consist of what we have referred to as feline enteric coronaviruses (FECVs) and feline infectious peritonitis viruses (FIPVs). FECVs cause a transient enteritis in kittens but no systemic illness. FIPVs, in contrast, cause a systemic and usually fatal disease syndrome characterized either by an exudative serositis or a disseminated granulomatous disease. Although the diseases they cause are quite different, FECVs and FIPVs are antigenically and morphologically indistinguishable from each other. FECVs have a strict tropism for mature intestinal epithelial cells and do not appear to replicate in macrophages. In contrast, FIPVs, appear to spread rapidly from the intestinal mucosa and replicate in macrophages. Experiments will be presented, and literature cited, that will allow us to make the following assumptions about the pathogenesis of FIPV infection: 1) FIPVs and FECVs represent a spectrum of viruses that differ only in infectivity (ability to evoke seroconversion following oral infection) and virulence (ability to cause FIP), 2) field isolates are generally nearer to FECVs in behavior than laboratory isolates made from animal passaged material, 3) immunity to FIPV appears to be of the premunition type and is maintained for as long as the infection persists in a reactivatable form, 4) strains of feline coronaviruses that do not cause systemic disease, such as FECVs or low virulence FIPVs, can actually sensitize cats to infection with virulent FIPV strains, 5) FeLV infection interferes with established FIP immunity and allows for the reactivation of disease in healthy carriers, 6) FIPV may be passaged from queen to kitten either in utero or during neonatal life, and 7) kittens infected by their mothers with FIPV do not usually develop FIP but become immune carriers of the virus for a period of 5-6 months; recovery from the carrier state is associated with a loss of premunition immunity.


title: [Management of a colon cancer patient infected with corona virus disease 2019].

text: OBJECTIVE To explore the feasibility of surgical treatment for cancer patients complicated with corona virus disease 2019 (COVID-19). METHODS The management and clinical outcome of a sigmoid cancer patient with COVID-19 were analyzed. RESULTS The inflammation indicators and fever of this patient were effectively controlled and the lung lesions remained stable after active anti-viral treatment, then the radical colorectomy was performed after the viral negative conversion for twice. CONCLUSIONS The case indicates that it may feasible to undergo radical tumor surgery for cancer patients with COVID-19 after the virus nucleic acid testing turns negative and more studies are needed to confirm this conclusion.


title: Reverse transcriptase PCR diagnostic assay for the coronavirus associated with severe acute respiratory syndrome.

text: Recent outbreaks of severe acute respiratory syndrome (SARS) have spurred intense research efforts around the world to deal with the serious threat to health posed by this novel coronavirus. A rapid, reliable diagnostic assay is needed for monitoring the spread of the disease. Here we report a method for eliminating false-negative results and increasing test sensitivity, based on the hypothesis that the message encoded by the nucleocapsid (N) gene is the most abundant during viral infection. Nasopharyngeal aspirates and stool samples were obtained from suspected SARS patients with major clinical symptoms and a significant history of close contact with infected patients. Total RNAs were extracted in a 96-well format, together with pig kidney epithelial (PK-15) cells as an internal control for extraction efficiency. PCR inhibitors were removed by ethanol precipitation, and a PCR for the pig beta-actin gene was used as a positive control for all clinical samples. Samples were analyzed by a reverse transcriptase PCR assay. Northern blot analysis was performed to demonstrate differences in subgenomic transcripts of the virus, and a real-time quantitative PCR was employed to compare the sensitivities of two loci (1b and N). The detection rate of the assay reached 44.4% on day 9 after the onset of the disease. The diagnostic PCR amplifying the N gene gave an average of a 26.0% (6.3 to 60.0%) stronger intensity signal than that for the 1b gene. In conclusion, the nucleocapsid gene represents an additional sensitive molecular marker for the diagnosis of the SARS coronavirus and can be further adapted for use in a high-throughput platform assay.


title: Canine influenza.

text: Canine influenza virus (CIV) is a newly identified, highly contagious respiratory pathogen of dogs. The clinical disease has high morbidity and low mortality. Diagnosis of canine influenza is based on acute and convalescent serum samples, history, and clinical signs. Phylogenetic analysis has shown that the etiologic agent is an influenza A virus that is closely related to the equine influenza A (H3N8) virus. Data collected thus far support transmission from horses to dogs with horizontal spread in the canine population. This interspecies jump and the close companionship of dogs and people warrant close monitoring of CIV for potential transmission to humans.


UK travellers warned after first suspected case of new syndrome.


title: [Flexible assertive community treatment (FACT) as part of a community (health) network].

text: BACKGROUND Community-based care for people with severe mental illness increasingly requires far-reaching cooperation between different domains. This cooperation must always be unique and local, and at the same time provide an answer to generic and nationally set goals. AIM: Offering new insights on collaboration within and between domains. METHOD: Reflection on developments in the social domain and specialist mental healthcare using relevant literature and recent (inter)national experiences. RESULTS: It seems possible to provide better integral care by allowing FACT-teams to network together with Social Support partners (e.g. by sharing financial and/or human resources). In this process, networks of care for people with serious mental illness (SMI), develop over various phases and realize new partnerships. The model fidelity scale for FACT-teams was adjusted to facilitate that process. CONCLUSIONS The new FACT model fidelity scale is ready to allow FACT-teams to explore flexible local solutions for partnerships to realize the much-needed multi-domain integrated community care for people with SMI.


Treat COVID-19 as Though It Is Airborne: It May Be.


title: Modulation of NB4 promyelocytic leukemic cell machinery by Anaplasma phagocytophilum.

text: Anaplasma phagocytophilum is a gram-negative obligate intracellular bacterium that persists within neutrophils. We assessed the impact of A. phagocytophilum infection in NB4 promyelocytic leukemic cells using high-density oligoarray, two-dimensional differential gel electrophoresis and liquid chromatography-mass spectrometry. Our Affymetrix data revealed that A. phagocytophilum altered the expression of transcription factors, cell adhesion molecules, signal transduction genes, and proinflammatory cytokines. However, the expression of Toll-like receptors, MYD88, RNF36, IRF3, and TBK1 and inhibitors of the NF-kappaB gene was not altered. A. phagocytophilum infection also altered the apoptotic program of NB4 cells and resulted in increased transcription of antiapoptotic genes (MCL1 and BFL1). The transcription and translation of iron-metabolism genes (light polypeptide ferritin chain, transferrin, and the transferrin receptor) were significantly altered, suggesting a possible link between A. phagocytophilum infection and iron metabolism. Our study clearly demonstrates multifactorial effects of A. phagocytophilum infection on NB4 promyelocytic leukemic cell machinery.


title: Bovine coronavirus 5'-proximal genomic acceptor hotspot for discontinuous transcription is 65 nucleotides wide.

text: Coronaviruses are positive-strand, RNA-dependent RNA polymerase-utilizing viruses that require a polymerase template switch, characterized as discontinuous transcription, to place a 5'-terminal genomic leader onto subgenomic mRNAs (sgmRNAs). The usually precise switch is thought to occur during the synthesis of negative-strand templates for sgmRNA production and to be directed by heptameric core donor sequences within the genome that match an acceptor core (UCUAAAC in the case of bovine coronavirus) near the 3' end of the 5'-terminal genomic leader. Here it is shown that a 22-nucleotide (nt) donor sequence engineered into a packageable bovine coronavirus defective interfering (DI) RNA and made to match a sequence within the 65-nt virus genomic leader caused a template switch yielding an sgmRNA with only a 33-nt minileader. By changing the donor sequence, acceptor sites between genomic nt 33 and 97 (identical between the DI RNA and the viral genome) could be used to generate sgmRNAs detectable by Northern analysis (approximately 2 to 32 molecules per cell) by 24 h postinfection. Whether the switch was intramolecular only was not determined since a potentially distinguishing acceptor region in the DI RNA rapidly conformed to that in the helper virus genome through a previously described template switch known as leader switching. These results show that crossover acceptor sites for discontinuous transcription (i) need not include the UCUAAAC core and (ii) rest within a surprisingly wide 5'-proximal "hotspot." Overlap of this hotspot with that for leader switching and with elements required for RNA replication suggests that it is part of a larger 5'-proximal multifunctional structure.


title: Flow-independent dynamics in aneurysm (FIDA): pressure measurements following partial and complete flow impairment in experimental aneurysm model.

text: BACKGROUND There have been growing concerns regarding delayed aneurysm rupture subsequent to the flow-diverting stent deployment. Therefore, more investigations are needed regarding hemodynamic changes secondary to flow-diverting stent deployment. OBJECTIVE To study intra-aneurysmal and perianeurysmal pressures after partial and complete flow impairment into the aneurysm. METHODS A silicone model of an 8-mm-sized aneurysm (neck diameter: 5 mm, vessel size: 4 mm) was used. The aneurysm wall was encapsulated and sealed within a 5 ml syringe filled with saline and a pressure sensor guide wire (ComboWire, Volcano Corp.) to detect pressure changes in the perivascular compartment (outer aneurysm wall). A second pressure sensor guide wire was advanced inside the aneurysm sac. Both pressure sensors were continuously measuring pressure inside and outside the aneurysm under pulsatile flow under the following conditions: 1) baseline (reference); 2) a 16 mm by 3.75 mm flow-diverting stent (ev3/Covidien Vascular, Mansfield, MA) deployed in front of the aneurysm; 3) two flow-diverting stents (16 mm by 3.5 mm) were deployed; and 4) a covered stent (4 mm by 16 mm VeriFlex coronary artery stent covered with rubber sheet) was deployed. RESULTS Mean (±SD) baseline pressures inside and outside the aneurysm were 53.9 (±2.4) mmHg (range 120-40 mmHg) and 15.4 (±0.7) mmHg (range 40-8mmHg), respectively. There was no change in pressure inside and outside the aneurysm after deploying the first and second flow-diverting stents (partial flow impairment) and it remained at 53.9 (±2.7) mmHg and 14.9 (±1) mmHg for the pressure inside and outside the aneurysm, respectively. The pressure recording from outside the aneurysm dropped from 15.4 (±0.7) mmHg to 0.3 (±0.7) mmHg after deploying the covered stent (complete flow impairment). There was no change in pressure inside the aneurysm after deploying the covered stent. Mean (±SD) pressure within the aneurysm was 55.1 (±1.7) mmHg and it remained 54.7 (±1.7) mmHg after covered stent deployment. CONCLUSION Our findings suggest a major discordance between the pressures within the aneurysm and partial or complete flow impairment (flow independent). The outer wall pressure is reduced after covered stent placement. These finding may assist clinicians in better understanding of aneurysm hemodynamics and rupture after flow-diverting stent deployment.


title: [Medical students at the bedside of COVID-19 patients : motivations and challenges].

text: The SARS-CoV-2 pandemic is putting our healthcare system under exceptional pressure, given the number of affected patients. In a context of limited human healthcare resources, senior medical students represent a valuable workforce that can quickly be mobilized for patient care. This is the approach followed in Switzerland and other countries, in several outpatient structures or inpatient services, including the Department of Internal Medicine, of the Lausanne University Hospital (CHUV). In this article, we first give the floor to students who responded to our call. We conclude with important considerations in terms of students' clinical supervision. It is reminded that the involvement of students in the care of COVID-19 patients should only occur on a vo luntary basis.


title: SARS molecular epidemiology: a Chinese fairy tale of controlling an emerging zoonotic disease in the genomics era.

text: Severe acute respiratory syndrome (SARS) was the first natural disaster that challenged the Chinese people at the beginning of the twenty-first century. It was caused by a novel animal coronavirus, never recognized or characterized before. This SARS coronavirus (SARS-CoV) exploited opportunities provided by 'wet markets' in southern China to adapt to the palm civet and human. Under the positive selection pressure of human host, certain mutated lineages of the virus became readily transmissible between humans and thus caused the epidemic of 2002-2003. This review will provide first-hand information, particularly from Guangdong, China, about the initial epidemiology, the identification of the aetiological agent of the disease, the molecular evolution study of the virus, the finding of SARS-like CoV in horseshoe bats and the mechanistic analysis for the cross-host tropism transition. The substantial scientific contributions made by the Chinese scientists towards understanding the virus and the disease will be emphasized. Along with the description of the scientific discoveries and analyses, the significant impact of these researches upon the public health measurement or regulations will be highlighted. It is aimed to appreciate the concerted and coordinated global response that controlled SARS within a short period of time as well as the research strategy and methodology developed along with this process, which can be applied in response to other public health challenges, particularly the future emerging/re-merging infectious diseases.


title: Characterization of high density lipoprotein-bound and soluble RT6 released following administration of anti-RT6.1 monoclonal antibody.

text: RT6 is a rat lymphocyte glycosylphosphatidylinositol (GPI)-anchored alloantigen with nicotinamide adenine dinucleotide (NAD) glycohydrolase (NADase) and auto-ADP-ribosyltransferase activities. RT6 may have immunoregulatory properties based in part on the observation that injection of diabetes-resistant (DR)-BB rats with depleting doses of anti-RT6.1 mAb induced autoimmune diabetes and thyroiditis. We now report that injection of DR-BB rats with anti-RT6.1 mAb increased plasma NADase activity, which localized, by fluid phase liquid chromatography fractionation, to the high density lipoprotein (HDL) fraction. Following ultracentrifugation in high salt, however, RT6 was found in the nonlipoprotein fraction, where it existed, under nondenaturing conditions, as a 200-kDa complex and, by SDS-PAGE, as a 30- to 36-kDa species. Thy-1, another GPI-linked protein, and proteins that reacted with anti-GPI-oligosaccharide Abs also translocated from HDL to the nonlipoprotein fraction under similar conditions. Injection of anti-RT6.1 mAb into thymectomized DR and diabetes-prone-BB rats increased soluble RT6 to levels comparable to those observed in euthymic DR-BB rats, suggesting that HDL-bound RT6 is not derived from peripheral lymphocytes. In agreement, NADase activity in the plasma of eviscerated DR-BB rats did not increase following injection of anti-RT6 mAb. These data suggest that HDL is a carrier of plasma RT6 and other GPI-linked proteins, with equilibrium between the lipoprotein and nonlipoprotein fractions being salt dependent. Since GPI-linked proteins in HDL can transfer to cells in a functionally active form, the presence of RT6 in HDL is consistent with it having a role in signaling in nonlymphoid cells.


title: Improving door-to-balloon times in primary percutaneous coronary intervention for acute ST-elevation myocardial infarction: the value of an audit-driven quality initiative.

text: INTRODUCTION The study was designed to reduce door-to-balloon times in primary percutaneous coronary intervention for patients presenting to the Emergency Department with acute ST-elevation myocardial infarction, using an audit as a quality initiative. MATERIALS AND METHODS A multidisciplinary work group performed a pilot study over 3 months, then implemented various process and work-flow strategies to improve overall door-to-balloon times. RESULTS AND CONCLUSION We developed a guideline-based, institution-specific written protocol for triaging and managing patients who present to the Emergency Department with symptoms suggestive of STEMI, resulting in shortened median door-to-balloon times from 130.5 to 109.5 minutes (P<0.001).


title: Avian flu and possible human pandemic.

text: Avian flu is affecting the poultry animals world over since first outbreak in 1997 in Hong Kong and has resulted in 92 human deaths and culling of more than 150 million poultry animals in Asia and Europe. The loss to the economy has also been enormous. 13 new countries, including India, reported occurrence of the disease in poultry animals in February 2006 only, to the World Health Organisation. This rapid rate of spread of virus along with notoriety of the virus for frequent genetic re-assortment, which might enable H5N1 to infect human beings, threatens of possible influenza pandemic since the last pandemic in 1968. The human influenza caused by this subtype of the virus (H5N1) has high case fatality of 54% and majority of affected humans are between the age of 5 to 23 years. Lack of effective vaccine, poor knowledge about treatment, and with scarcity of public health measures in developing countries are major causes of concern. The real threat of impending pandemic can be avoided only if we act immediately on the basis of currently available source of information and apply scientific knowledge rationally for containment and prevention of bird flu and treat human cases promptly.


The fetal origins of adult disease.


State-of-the-art psychiatric diagnosis.


title: Severe acute respiratory syndrome coronavirus open reading frame (ORF) 3b, ORF 6, and nucleocapsid proteins function as interferon antagonists.

text: The severe acute respiratory syndrome coronavirus (SARS-CoV) is highly pathogenic in humans, with a death rate near 10%. This high pathogenicity suggests that SARS-CoV has developed mechanisms to overcome the host innate immune response. It has now been determined that SARS-CoV open reading frame (ORF) 3b, ORF 6, and N proteins antagonize interferon, a key component of the innate immune response. All three proteins inhibit the expression of beta interferon (IFN-beta), and further examination revealed that these SARS-CoV proteins inhibit a key protein necessary for the expression of IFN-beta, IRF-3. N protein dramatically inhibited expression from an NF-kappaB-responsive promoter. All three proteins were able to inhibit expression from an interferon-stimulated response element (ISRE) promoter after infection with Sendai virus, while only ORF 3b and ORF 6 proteins were able to inhibit expression from the ISRE promoter after treatment with interferon. This indicates that N protein inhibits only the synthesis of interferon, while ORF 3b and ORF 6 proteins inhibit both interferon synthesis and signaling. ORF 6 protein, but not ORF 3b or N protein, inhibited nuclear translocation but not phosphorylation of STAT1. Thus, it appears that these three interferon antagonists of SARS-CoV inhibit the interferon response by different mechanisms.


title: The hemagglutinin-esterase of mouse hepatitis virus strain S is a sialate-4-O-acetylesterase.

text: By comparative analysis of the hemagglutinin-esterase (HE) protein of mouse hepatitis virus strain S (MHV-S) and the HE protein of influenza C virus, we found major differences in substrate specificities. In striking contrast to the influenza C virus enzyme, the MHV-S esterase was unable to release acetate from bovine submandibulary gland mucin. Furthermore, MHV-S could not remove influenza C virus receptors from erythrocytes. Analysis with free sialic acid derivatives revealed that the MHV-S HE protein specifically de-O-acetylates 5-N-acetyl-4-O-acetyl sialic acid (Neu4, 5Ac2) but not 5-N-acetyl-9-O-acetyl sialic acid (Neu5,9Ac2), which is the major substrate for esterases of influenza C virus and bovine coronaviruses. In addition, the MHV-S esterase converted glycosidically bound Neu4,5Ac2 of guinea pig serum glycoproteins to Neu5Ac. By expression of the MHV esterase with recombinant vaccinia virus and incubation with guinea pig serum, we demonstrated that the viral HE possesses sialate-4-O-acetylesterase activity. In addition to observed enzymatic activity, MHV-S exhibited affinity to guinea pig and horse serum glycoproteins. Binding required sialate-4-O-acetyl groups and was abolished by chemical de-O-acetylation. Since Neu4,5Ac2 has not been identified in mice, the nature of potential substrates and/or secondary receptors for MHV-S in the natural host remains to be determined. The esterase of MHV-S is the first example of a viral enzyme with high specificity and affinity toward 4-O-acetylated sialic acids.


title: "Keep it short and sweet": Improving risk communication to family physicians during public health crises.

text: OBJECTIVE To identify recommendations from family physicians in Canada on how public health agencies and professional organizations might improve future crisis and emergency risk communications. DESIGN Qualitative content analysis. SETTING Canada. PARTICIPANTS Sixteen family physicians who have experienced a public health crisis. METHODS Semistructured interviews were conducted with 16 family physicians practising in various regions across Canada who had experienced what they defined as a public health crisis. These events included environmental crises, like forest fires and hurricanes, and infectious disease crises, like the SARS (severe acute respiratory syndrome) and H1N1 outbreaks. Interview transcripts were coded using an inductive qualitative content analysis method, specifically focusing on recommendations from participants on how to improve risk communication to family physicians in the event of a future public health crisis. MAIN FINDINGS Based on their personal experiences, participants had many explicit recommendations on how to improve risk communication strategies in the event of a future public health crisis. These included having a single trusted source of information; having timely and succinct communication; having consideration for learners; ensuring access to information for all physicians; improving public health and family medicine collaboration; having crisis information for patients; and creating communication infrastructure before a crisis occurs. CONCLUSION This research provides thoughtful and varied considerations and advice from practising family physicians on how to improve risk communication from public health agencies and professional organizations to this group in the event of a public health crisis. With improved communications between these bodies and family physicians, practitioners will be better informed and prepared to provide the best possible care to their patient populations during such events.


title: Non-invasive longitudinal imaging of tumor progression using an (111)indium labeled CXCR4 peptide antagonist.

text: The chemokine receptor 4 (CXCR4) is a biomarker that is over-expressed in ductal carcinoma in situ (DCIS). Hence, CXCR4-targeted (molecular) imaging approaches may have diagnostic value in such a challenging, premalignant lesion. The indium labeled CXCR4 peptide-antagonist, (111)In-DTPA-Ac-TZ14011, was used to visualize CXCR4-expression in a mammary intraepithelial neoplastic outgrowth (MIN-O) mouse tumor model resembling human DCIS. MIN-O lesion development was longitudinally monitored using SPET/CT and tracer uptake was compared to uptake in control lesions. Expression of CXCR4 was validated using immunohistochemistry and flow cytometric analysis. The uptake of (111)In-DTPA-Ac-TZ14011 was related to tumor angiogenesis using (111)In-cDTPA-[RGDfK]. Twenty-four hours after tracer injection, MIN-O lesions could be discriminated from low CXCR4-expressing control tumors, while the degree of angiogenesis based on the α(v)β(3) integrin expression in both tumor types was similar. The uptake of (111)In-DTPA-Ac-TZ14011 in early MIN-O lesions was significantly lower than in larger intermediate and late-stage lesions, two-and-a-half-times (p=0.03) and seven-times (p=0.002), respectively. Intermediate and late stage lesions show a higher degree of membranous CXCR4-staining at immunohistochemistry and flow cytometric analysis. From this study we can conclude that (111)In-DTPA-Ac-TZ14011 can be used to visualize the CXCR4-expression in MIN-O lesions longitudinally.


title: Molecular characterization confirms the presence of a divergent strain of canine coronavirus (UWSMN-1) in Australia.

text: Canine coronavirus (CCV) UWSMN-1 was originally identified from an outbreak of fatal gastroenteritis in breeding colonies. In this report, we examined whether UWSMN-1 represents a novel divergent strain or is the result of recombination events between canine and feline coronavirus strains. Sequencing of various regions of the spike and polymerase genes confirms that UWSMN-1 is widely divergent from other CCV and feline coronavirus strains. These data raise the possibility that this strain is the first member of a novel third subtype of CCV.


title: Transnasal approach to the orbital apex and cavernous sinus.

text: OBJECTIVES The aim of this study was to provide the anatomic rationale for a transnasal approach to the orbital apex and cavernous sinus, and to evaluate its applicability and efficiency. METHODS One hundred patients with lesions of the orbital apex, cavernous sinus, optic nerve, clivus, parapharyngeal space, infratemporal fossa, or pterygopalatine fossa were reviewed over a 10-year period. All patients underwent an endoscopic transnasal approach to the orbital apex and cavernous sinus. The surgical technique required a standard endoscopic sinus surgery set. The possible complications were recorded and classified as intraoperative or postoperative. RESULTS There were complications in 8 cases: 4 intraoperative and 4 postoperative. The intraoperative complications included rupture of the internal carotid artery in 1 patient and cerebrospinal fluid leak in 3 patients. All intraoperative complications were resolved during surgery. The postoperative complications were transitory eyelid ptosis in 2 patients (resolved in 6 months) and transitory diplopia with immediate deficit of the medial rectus muscle in 2 patients (completely resolved in 1 month). CONCLUSIONS With the use of this technique, the surgeon can precisely identify the position of the surgical instrument without losing his or her way, thereby significantly reducing the rate of complications.


title: Analysis of coronavirus transcription regulation.

text: Insertion of an intergenic region from murine coronavirus mouse hepatitis virus (MHV) into an MHV defective interfering (DI) RNA led to transcription of subgenomic DI RNA in helper virus-infected cells. Using this system we studied how two intergenic regions positioned in close proximity affected subgenomic RNA synthesis. When two intergenic regions were separated by more than 100 nt, slightly less of the larger subgenomic DI RNA (synthesized from the upstream intergenic region) was made; this difference was significant when the intergenic region separation was less than about 35 nucleotides. Deletion of sequences flanking the two intergenic regions inserted in close proximity did not affect transcription. No significant change in the ratio of the two subgenomic DI RNAs was observed when the sequence between the two intergenic regions was altered. Removal of the downstream intergenic region restored transcription of the larger subgenomic DI RNA. These results demonstrated the downstream intergenic sequence was suppressing subgenomic DI RNA synthesis from the upstream intergenic region.


title: Survey of hospital healthcare personnel response during a potential avian influenza pandemic: will they come to work?

text: INTRODUCTION In order to prepare for pandemics, it is important to assess the likelihood that hospital personnel would report to work and to identify the issues that may affect this decision. OBJECTIVE To survey hospital personnel regarding their attendance at work in the hypothetical event of avian influenza pandemic, and what factors might influence this decision. METHODS A voluntary, confidential, institutional review board-approved survey was offered to a convenience sample of hospital workers regarding their willingness to report to work and what issues would be important in making this decision. Surveys not returned and individuals declining to participate were recorded. RESULTS Of 187 surveys offered, 169 were completed (90% response rate): 34% were doctors, 33% were nurses, and 33% were clerical and other associates (other). The average age of the participants was 38 years, and 32% were males. Participants were asked: "In the event of an avian pandemic, and patients were being treated at this hospital, would you report to work as usual?". Of those who responded to the survey, 50% reported "yes", 42% reported "maybe", and 8% reported "no". Doctors were more likely than nurses or others to respond "yes" (73%), as were males (66%). For the "maybe" responders, the most important factor (83%) was: "How confident I am that the hospital can protect me". For 19% of the "maybe" responders, financial incentives would not make a difference for them to work, even up to triple pay. CONCLUSIONS Personnel absenteeism during a pandemic due to fear of contracting an illness may result in a significant personnel shortage. Ensuring worker confidence in adequate personal protection may be more important than financial incentives.


title: Field study of bovine coronavirus vaccine enriched with hemagglutinating antigen for winter dysentery in dairy cows.

text: A field study of a vaccine; prepared by solubilizing cells infected with bovine coronavirus, Triton X-100, and mixing with an oil adjuvant, was performed at 9 farms over 4 prefectures. The cattle tested were Holstein dairy cows aged 2 to 10 years. A vaccination group consisted of 157 animals (including 132 pregnant cows) and a non-vaccinated control group consisted of 50 animals. The cows received 2 intramuscular injections of vaccine (2 mL) at 3-week intervals. Vaccinated cows did not develop abnormalities, such as a decrease in milk production volume, and all pregnant animals calved normally. The geometric mean of the hemagglutination inhibition antibody titer was 34.2 before vaccination in test cows. The titer had increased to 105.6, 3 weeks after the 1st injection and peaked at 755.6, 1 month after the 2nd injection. A high antibody titer persisted at 396.0; 241.0; and 201.5, at 3, 6, and 9 months after the 2nd injection, respectively. This confirms the safety and high antibody-response induced by this prototype vaccine. Therefore, this vaccine may be useful for the prevention of winter dysentery caused by bovine coronavirus infection.


Professional development for prospective epidemiology teachers in grades 6-12.


title: Public health awareness of emerging zoonotic viruses of bats: a European perspective.

text: Bats classified in the order Chiroptera are the most abundant and widely distributed non-human mammalian species in the world. Several bat species are reservoir hosts of zoonotic viruses and therefore can be a public health hazard. Lyssaviruses of different genotypes have emerged from bats in America (Genotype 1 rabies virus; RABV), Europe (European bat lyssavirus; EBLV), and Australia (Australian bat lyssavirus; ABLV), whereas Nipah virus is the most important recent zoonosis of bat origin in Asia. Furthermore, some insectivorous bat species may be important reservoirs of SARS coronavirus, whereas Ebola virus has been detected in some megachiropteran fruit bats. Thus far, European bat lyssavirus (EBLV) is the only zoonotic virus that has been detected in bats in Europe. New zoonotic viruses may emerge from bat reservoirs and known ones may spread to a wider geographical range. To assess future threats posed by zoonotic viruses of bats, there is a need for accurate knowledge of the factors underlying disease emergence, for an effective surveillance programme, and for a rapid response system. In Europe, primary efforts should be focussed on the implementation of effective passive and active surveillance systems for EBLVs in the Serotine bat, Eptesicus serotinus, and Myotis species (i.e., M. daubentonii and M. dasycneme). Apart from that, detection methods for zoonotic viruses that may emerge from bats should be implemented. Analyses of data from surveillance studies can shed more light on the dynamics of bat viruses, (i.e., population persistence of viruses in bats). Subsequently, studies will have to be performed to assess the public health hazards of such viruses (i.e., infectivity and risk of infection to people). With the knowledge generated from this kind of research, a rapid response system can be set up to enhance public health awareness of emerging zoonotic viruses of bats.


title: Microbiological monitoring of laboratory pigs.

text: Purpose-bred minipigs, are often used as the non-rodent species in toxicology. Infections may interfere with animal experiments, and there are no scientific reasons why the non-rodent species should be of a lower microbiological quality than the rodent species. Therefore, a system for health monitoring of pigs was developed in order to raise the quality of laboratory pigs to the level of laboratory rodents. This system, which includes screening for several viruses, bacteria and ecto- and endoparasites, was used for monitoring minipigs from a barrier unit with the same standards applied to rodents units. In these pigs only rotaviruses are found, which was shown by both serological antibody detection and by detection of rotaviral antigen in faeces. In minipigs from another unit with far less hygienic protection rotaviruses were also found along with certain influenza- and coronaviruses, as well as Pasteurella spp. It is concluded, that it is possible to raise pigs of a microbiological quality comparable to the quality of rats and mice, and that advanced microbiological monitoring in pigs will reveal useful information.


title: Respiratory disease associated with bovine coronavirus infection in cattle herds in Southern Italy.

text: Four outbreaks of bovine respiratory disease (BRD) associated with bovine coronavirus (BCoV) infection in Italian cattle herds were reported. In 3 outbreaks, BRD was observed only in 2-3-month-old feedlot calves, whereas in the remaining outbreak, lactating cows, heifers, and calves were simultaneously affected. By using reverse transcription polymerase chain reaction (RT-PCR), BCoV RNA was detected in all outbreaks without evidence of concurrent viral pathogens (i.e., bovine respiratory syncytial virus, bovine herpesvirus type 1, bovine viral diarrhea virus, bovine parainfluenza virus). Common bacteria of cattle were recovered only from 2 outbreaks of BRD: Staphylococcus spp. and Proteus mirabilis (outbreak 1) and Mannheimia haemolytica (outbreak 4). A recently established real-time RT-PCR assay showed that viral RNA loads in nasal secretions ranged between 3.10 x 10(2) and 7.50 x 10(7) RNA copies/microl of template. Bovine coronavirus was isolated from respiratory specimens from all outbreaks except outbreak 1, in which real-time RT-PCR found very low viral titers in nasal swabs.


title: [Middle-East respiratory syndrome].

text: MERS-CoV is the sixth type of corona virus to cause disease in humans. This virus can cause severe respiratory infections, particularly in patients with underlying conditions. Although dromedary camels appear to be the most important source in primary cases, nosocomial transmission has proved to be a major cause of secondary infections. In accordance with the case definitions formulated by the Dutch National Institute for Public Health and the Environment (RIVM), in those patients who present with lower respiratory infections within 14 days of visiting the Arabian Peninsula, MERS-CoV should be considered.


title: Mechanisms of lymphocyte loss in SARS coronavirus infection.

text: 1. Human lymphocytes and monocytes are not permissive to productive SARS coronavirus (SARS-CoV) infection in vitro. 2. Challenge of lymphocytes and monocytes with infectious SARS-CoV, inactivated virions, and receptor-binding fragment of spike protein does not trigger apoptosis. 3. Direct infection/interaction between viruses and lymphocytes/monocytes is unlikely to be the cause of lymphopaenia in SARS patients. 4. Lymphopaenia in SARS patients is likely to result from indirect mechanisms secondary to the viral infection.


In Memoriam: Robert M. Chanock, MD, 1924–2010.


title: Surgical management of symptomatic simple hepatic cysts.

text: The authors present three cases of symptomatic, large, benign, nonparasitic hepatic cysts. The diagnosis was determined by US and CT scan, the latter enabling differential diagnosis with neoplastic or hydatid cysts. All patients were treated with open hepatic resection. In 2 cases, laparoscopy was performed to enable complete diagnosis. The authors used LigaSure™ (Covidien, USA) instrument, avoiding bleeding complications and reducing surgery time. Histological examination confirmed the diagnosis of benign cysts. CT follow-up at 6 months and 1 year demonstrated the efficacy of the surgery, with no recurrences.


title: Perceptions of infection control practices among health professionals.

text: Infection control practice is a cornerstone of modern health care. However, there is minimal research into health professionals' perception of infection control practices and how those perceptions influence staff compliance with recommended protocols. The objective of this study was to explore health care professionals' perceptions of infection control practices in relation to the management of infectious diseases. A grounded theory approach was used as the research framework. Semi-structured interviews were completed with a sample of 16 nurses and doctors working at hospitals in Western Australia. Four major categories emerged from the data. These were: knowledge, culture, conflict, and risk assessment. The findings indicate the importance of both individual and organisational factors in determining clinicians' levels of compliance with recommended infection control practices. Identification of the factors that influence health professionals' level of compliance can be used to develop strategies to support long-term compliance with infection control practices.


title: Montelukast reduces asthma exacerbations in 2- to 5-year-old children with intermittent asthma.

text: The PREVIA study was designed to investigate the role of montelukast, a leukotriene receptor antagonist, in the prevention of viral-induced asthma exacerbations in children aged 2 to 5 years with a history of intermittent asthma symptoms. The study was a 12-month multicenter, double-blind, parallel-group study of patients with asthma exacerbations associated with respiratory infections and minimal symptoms between episodes. Patients were randomized to receive oral montelukast 4 or 5 mg (depending on age) (n = 278) or placebo (n = 271) once per day for 12 months. Caregivers recorded children's symptoms, beta-agonist use, and health care resource use in a diary card. Over 12 months of therapy, montelukast significantly reduced the rate of asthma exacerbations by 31.9% compared with placebo. The average rate of exacerbation episodes per patient was 1.60 episodes per year on montelukast compared with 2.34 episodes on placebo. Montelukast also delayed the median time to first exacerbation by approximately 2 months (p = 0.024), and the rate of inhaled corticosteroid courses (p = 0.027) compared with placebo. Montelukast effectively reduced asthma exacerbations in 2- to 5-year-old patients with intermittent asthma over 12 months of treatment and was generally well tolerated.


title: Suppression of coronavirus replication by inhibition of the MEK signaling pathway.

text: We previously demonstrated that infection of cultured cells with murine coronavirus mouse hepatitis virus (MHV) resulted in activation of the mitogen-activated protein kinase (Raf/MEK/ERK) signal transduction pathway (Y. Cai et al., Virology 355:152-163, 2006). Here we show that inhibition of the Raf/MEK/ERK signaling pathway by the MEK inhibitor UO126 significantly impaired MHV progeny production (a reduction of 95 to 99% in virus titer), which correlated with the phosphorylation status of ERK1/2. Moreover, knockdown of MEK1/2 and ERK1/2 by small interfering RNAs suppressed MHV replication. The inhibitory effect of UO126 on MHV production appeared to be a general phenomenon since the effect was consistently observed in all six different MHV strains and in three different cell types tested; it was likely exerted at the postentry steps of the virus life cycle because the virus titers were similarly inhibited from infected cells treated at 1 h prior to, during, or after infection. Furthermore, the treatment did not affect the virus entry, as revealed by the virus internalization assay. Metabolic labeling and reporter gene assays demonstrated that translation of cellular and viral mRNAs appeared unaffected by UO126 treatment. However, synthesis of viral genomic and subgenomic RNAs was severely suppressed by UO126 treatment, as demonstrated by a reduced incorporation of [3H]uridine and a decrease in chloramphenicol acetyltransferase (CAT) activity in a defective-interfering RNA-CAT reporter assay. These findings indicate that the Raf/MEK/ERK signaling pathway is involved in MHV RNA synthesis.


title: Ribonucleoprotein-like structures from coronavirus particles.

text: The structure of the ribonucleoprotein (RNP) complex of three coronaviruses was investigated. A single-stranded helix of diam. 14 to 16 nm and up to 320 nm in length was released from disrupted particles of human coronavirus strain 229E and mouse hepatitis virus strain 3 after incubation in mild conditions. The helical complexes appeared to be composed of globular subunits with long axes of 5 to 7 nm surrounding a hollow core of diam. 3 to 4 nm. The complexes were shown to be sensitive to both pancreatic RNase and to pronase. No undegraded internal component was obtained from disrupted avian infectious bronchitis virus particles. We conclude that these structures are RNP complexes. The similarity between these RNPs and those of other large lipid containing RNA viruses is discussed.