title: Assessment of celecoxib poly(lactic-co-glycolic) acid nanoformulation on drug pharmacodynamics and pharmacokinetics in rats.

text: OBJECTIVE Celecoxib (CEL) is a nonsteroidal anti-inflammatory drug (NSAID) showing selective cycloxygenase-2 inhibition. While effective as a pain reducer, CEL exerts some negative influence on renal and gastrointestinal parameters. This study examined CEL pharmacodynamics and pharmacokinetics following drug reformulation as a poly(lactic-co-glycolic) acid nanoparticle (NP). MATERIALS AND METHODS Rats were administered either vehicle (VEH) (methylcellulose solution), blank NP, 40 mg/kg CEL in methylcellulose, or an equivalent NP dose (CEL-NP). Plasma and urine (over 12 hrs) samples were collected prior to and post-treatment. The mean percent change from baseline of urine flow rate along with electrolyte concentrations in plasma and urine were assessed based on 100 g body weight. Using tissues collected 24 hrs post-treatment, gastrointestinal inflammation was estimated through duodenal and gastric prostaglandin E2 (PGE2) and duodenal myeloperoxidase (MPO) levels; while kidney tissue was examined for dilatation and necrosis. CEL concentration was assayed in renal tissue and plasma utilizing high-performance liquid chromatography. RESULTS Although there were significant changes when comparing CEL and CEL-NP to VEH in plasma sodium concentration and potassium excretion rate, there was no significant variation between CEL and CEL-NP. There was a significant reduction of protective duodenal PGE2 in CEL compared to VEH (p = 0.0088) and CEL-NP (p = 0.02). In the CEL-NP formulation, t1/2, Cmax, AUC0-∞, and Vd/F increased significantly when compared to CEL. CONCLUSIONS At the observed dosage and duration, CEL-NP may not affect CEL-associated electrolyte parameters in either plasma or urine; however, it does provide increased systemic exposure while potentially alleviating some gastrointestinal outcomes related to inflammation.


title: Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry.

text: Severe acute respiratory syndrome (SARS) is caused by an emergent coronavirus (SARS-CoV), for which there is currently no effective treatment. SARS-CoV mediates receptor binding and entry by its spike (S) glycoprotein, and infection is sensitive to lysosomotropic agents that perturb endosomal pH. We demonstrate here that the lysosomotropic-agent-mediated block to SARS-CoV infection is overcome by protease treatment of target-cell-associated virus. In addition, SARS-CoV infection was blocked by specific inhibitors of the pH-sensitive endosomal protease cathepsin L. A cell-free membrane-fusion system demonstrates that engagement of receptor followed by proteolysis is required for SARS-CoV membrane fusion and indicates that cathepsin L is sufficient to activate membrane fusion by SARS-CoV S. These results suggest that SARS-CoV infection results from a unique, three-step process: receptor binding and induced conformational changes in S glycoprotein followed by cathepsin L proteolysis within endosomes. The requirement for cathepsin L proteolysis identifies a previously uncharacterized class of inhibitor for SARS-CoV infection.


The Krever Commission--10 years later.


Note from the editors: MERS-CoV - the quest for the reservoir continues.


title: [The clinical characteristics and staging of severe acute respiratory syndrome].

text: OBJECTIVE To investigate the clinical characteristics and to initiate a clinical staging of severe acute respiratory syndrome (SARS). METHODS Retrospective analysis was conducted in the clinical symptoms, physical signs and the results of laboratory examinations from 1170 cases with SARS in Beijing, and the clinical characteristics in different stages of the disease were compared. RESULTS The initial symptom of SARS was pyrexia and the temperature was > 38 degrees C. The natural course of fever was about 14 days. In almost all cases, the respiratory symptoms and systemic toxic manifestations were observed. They came to a climax at the second week and then decreased or nearly disappeared after the third week. The physical signs of SARS were not obvious. The moist rales were observed in 43.3% of patients. Hypoxemia was a common characteristic in SARS. The decrease in partial pressure of oxygen in artery and oxygen saturation in pulse oximeter with normal partial pressure of carbon dioxide was found in most patients at the second week. Abnormal chest X-ray including infiltration and consolidation shadows were seen in 100% of patients. The abnormal images could be found at the first day, enlarged during the second week (to a climax at the 8th or 9th day), and then recovered from the 2 week. The amounts of CD(4)(+), CD(8)(+), and CD(3)(+) of peripheral blood were decreased at the early stage and recovered after 2 or 3 weeks. Some patients suffered from temporary multiple organ dysfunctions (mainly impairments of liver and myocardium). CONCLUSION The main clinical manifestations of SARS included respiratory and systemic toxic symptoms. The typical course of the disease was about 4 weeks. The first week could be considered as early stage, the second week as fastigium stage, and from the next two weeks as recovery stage.


title: Effect of chicken antibodies on inflammation in human lung epithelial cell lines.

text: OBJECTIVES As an alternative therapeutic approach for the prevention and treatment of bacterial infections with P. aeruginosa of cystic fibrosis (CF) patients, chicken yolk antibodies (IgY) could be used. The most significant advantage of IgY, in contrast to mammalian IgG, consists in the fact, that when bound to the antigen, they usually do not induce inflammatory reaction. In addition, the simplicity of egg production and the ease of IgY preparation makes this kind of antibody an excellent tool for passive immunization. Thus, the aim of our project was to study the effect of IgY and its Fab fragment on the potential induction of pro-inflammatory reactions in lung epithelial cells. METHODS Chicken IgY were prepared from pooled egg yolks. Fab fragmens of IgY were purified from the papain digest of IgY using DEAE-Sephacel ion exchange chromatography. Their purity was verified by SDS electrophoresis in polyacrylamide gel. Immortalized human cell lines, CuFi (CF patient) and NuLi (healthy subject), and A549 (human adenocarcinoma cells) were exposed to IgY, Fab, OVA, LPS (positive control), PBS (negative control), and human and goat IgG for 24 hours. The concentration of pro-inflammatory cytokines TNF-α, IL-1β, IL-6 and GM-CSF were determined in cell media using the BioPlex method, which enables the quantification of multiple analytes simultaneously in one sample. RESULTS Our results show that i) the Fab fragment induced levels of some proinflammatory cytokines, when compared to the PBS control, whereas ii) chicken IgYs did not induce any notable production of pro-inflammatory cytokines in contrast to intense effect of LPS on TNF-α and GM-CSF. In summary, our data show that levels of all cytokines are comparable with physiological values in human serum except of IL-1β, which concentration in cell medium was markedly elevated by Fab fragment. CONCLUSIONS The present data indicate that IgY are not inflammatory for lung cells and thus they are possibly applicable for prevention of airway bacterial infections.


title: Prevalence of antibodies against canine parvovirus and canine distemper virus in wild coyotes in southeastern Colorado.

text: Serum from 72 wild coyotes (Canis latrans) in southeastern Colorado (USA) was collected and analyzed for prevalence of antibody to canine parvovirus (CPV) and canine distemper virus (CDV) from 1985 to 1988. The prevalence of antibodies to CPV and CDV was 71% and 57%, respectively, for the 4 yr of the study. Prevalence of antibody to CPV did not differ among years, between sexes, or with age. Prevalence of antibody to CDV did not differ among years or between sexes, but was significantly higher in adults (62%) than juveniles (33%). Prevalence of antibodies against CPV and CDV in southeastern Colorado was comparable to results reported in other serologic surveys in the western United States.


title: Recent developments on coronavirus main protease/3C like protease inhibitors.

text: Coronaviruses have been thrust into the spotlight by the recurring novel human coronavirus infections following the 2003 SARS pandemic. In the years since the initial SARS outbreak, the arsenal to fight this virus family has been significantly increased by the rapid growth of coronavirus research. Among the potential viral drug targets, coronavirus 3C like proteases (3Cl) have emerged as the most popular drug target. A number of patented inhibitors with promising clinical potential have been developed via different methods of drug discovery, including virtual screening, natural product isolation and structure assisted rational drug design. This review serves as a summary of the progress in both the method of drug discovery and the related inhibitors against the coronavirus 3Cl protease.


title: Rapid increase in HIV rates--Orel Oblast, Russian Federation, 1999-2001.

text: During 1999-2001, the estimated number of cases of human immunodeficiency virus (HIV) reported officially in the Russian Federation increased approximately 16-fold, from 11,000 to 177,000. In 2001, of 49,434 HIV-infected persons for whom a risk factor was identified, 46,274 (94%) were injection-drug users (IDUs). However, the actual number of HIV-infected persons in Russia is estimated to be four to 10 times higher than reported. Rapid increases in HIV have been reported in urban areas (e.g., Kaliningrad, Moscow, and St. Petersburg) and also might be occurring in rural areas. During 1997-2000, HIV seroprevalence reportedly increased 33-fold in Orel Oblast, a predominantly rural, agricultural province (1999 population: 900,000) in central European Russia. To confirm and describe this increase and evaluate the risk for continued rapid increase of HIV, CDC collaborated with the Orel Oblast AIDS and Infectious Diseases Prevention Center (AIDS Center) to assess recent HIV trends and the prevalence of risk behaviors among IDUs in Orel Oblast. This report summarizes the results of that assessment, which indicate continued increases in HIV rates and underscore the need for interventions directed at IDUs and their sex partners to limit further spread of HIV.


title: Effects of Topical Antiseptic Solutions Used During Total Knee Arthroplasty on Suture Tensile Strength.

text: INTRODUCTION Irrigating a surgical wound with an antiseptic solution is commonly performed while suturing following a total knee arthroplasty (TKA) to help prevent wound complications. The purpose of this study was to: 1) evaluate the mean load to failure of different sutures, and 2) compare the mean load to failure of the sutures after soaking in four different antiseptic solutions. MATERIALS AND METHODS Load-to-failure tests were conducted on four sets of comparable sutures (eight sutures) from two different companies Ethicon Inc. (Somerville, New Jersey) and Covidien (Mansfield, Massachusetts). The four suture types included: 1) non-absorbable braided polyethylene, 2) absorbable braided glycolide or lactide polymer, 3) absorbable monofilament polydioxanone or polyglyconate, and 4) absorbable monofilament polyglecaprone or gylcomer. Sutures were tested for tensile strength at baseline (i.e., no solution; n=5 per suture), and were then soaked for five minutes in one of four different antiseptic solutions: 0.125% sodium hypochlorite, 4% chlorhexidine gluconate, 10% povidone-iodine, and a 1:1 ratio of 3% hydrogen peroxide and sterile water. Effects of the different solutions on individual sutures were assessed with analysis of variance, and pairwise comparison tests were performed with post-hoc Tukey tests. RESULTS For the controls, the mean failure loads for the type 1 sutures were 118.5 N and 120.3 N, for the type 2 sutures, 145.8 N and 155.4 N, the type 3 sutures, 103.8 N and 162.2 N, and the type 4 sutures, 86.9 N and 87.7 N. After being soaked in sodium hypochlorite, the mean failure load decreased for one of the type 2 sutures (mean difference, -12.8 N;p=0.003), while the other type 2 suture had a decreased failure load after soaking in povidone-iodine (mean difference, -10.3 N;p=0.041) and hydrogen peroxide (mean difference, -14.6 N;p=0.001). A type 1 suture had an increased load to failure after soaking in povidone-iodine (mean difference, 13.2 N;p<0.0001) and hydrogen peroxide (mean difference, 10.5 N;p<0.0001). CONCLUSION Certain sutures may have changes in their breaking point depending on what type of antiseptic solution is used for wound irrigation, but due to the small magnitude of change, this may not necessarily be clinically relevant.


title: Challenges in building health surveillance systems in saudi arabia.

text: This paper is aiming to briefly discuss the role of health surveillance system in strengthening public health at both the local and global level and the use of health informatics in effectively creating a database of health status for the population of Saudi Arabia. This review will specifically focus on the challenges that face the Kingdom of Saudi Arabia in order to effectively implement surveillance programs making use of advances in health information technology. Data collection was performed through a web-based retrieval of reports and articles and via an interview with an epidemiologist in the Saudi Ministry of Health Surveillance unit. Based on the results of this research, it was found that the use of technology has led to an improvement in communication between various stakeholders (e.g. clinicians, epidemiologists, and decision makers) by providing timely and accurate information needed for informed decision making. However, implementing an ideal model of surveillance systems in Saudi Arabia faces many challenges particularly in training healthcare providers to be qualified and competent enough to ensure the successful implementation of a disease surveillance system.


Exacerbations of chronic obstructive pulmonary disease: definition, aetiology and management.


title: Intravenous immunoglobulin G is remarkably beneficial in chronic immune dysschwannian/dysneuronal polyneuropathy, diabetes-2 neuropathy, and potentially in severe acute respiratory syndrome.

text: Chronic Immune Dysschwannian/Dysneuronal Polyneuropathy is an autoimmune peripheral-nerve and/or nerve-root disorder known to usually respond to intravenous immunoglobulin-G treatment. Benefit can involve any combination of motor-nerve fibers and large and small sensory-nerve fibers responsible for a progressively crippling, unbalancing, discomforting or painful disorder. "Diabetic neuropathy" is commonly considered untreatable. However, 81% of my 48 recently-summarized type-2 diabetes patients with polyneuropathy, adequately-treated with intravenous immunoglobulin-G, off-label, were relieved, sometimes completely, of various motor and sensory symptoms, including pain, thereby resembling Chronic Immune Dysschwannian/Dysneuronal Polyneuropathy. Spinal fluid protein in them is often elevated, higher values seeming to auger a better intravenous immunoglobulin-G response. Continuing the improvement requires continuing the intravenous immunoglobulin-G treatment, indicating both intravenous immunoglobulin-G responsiveness and dependency. The intravenous immunoglobulin-G responsive type-2 diabetes polyneuropathy usually is dysschwannian, sometimes mainly dysneuronal intravenous immunoglobulin-G, the most beneficial and safest treatment, is costly, but if intravenous immunoglobulin-G-treatability of a dysimmune component of type-2 diabetes neuropathy is overlooked, dismissed or rejected, as commonly happens, other costs are high regarding the patient's worsening morbidity and disability, and resultant need for increased medical care. A novel intravenous immunoglobulin-G regimen effective for fragile patients is Two Non-Consecutive-Days Every Week, using 0.4 gm/kg body wt/day. Possible molecular mechanisms of intravenous immunoglobulin-G benefit are discussed. I propose that a) there is a higher incidence of Chronic Immune Dysschwannian/Dysneuronal Polyneuropathy-like neuropathy in type-2 diabetes patients and in patients with a strong family history of type-2 diabetes, and b) the intravenous immunoglobulin-G-treatable neuropathy in type-2 diabetes can be brought on by the genetico-diabetoid-2 state. The genetic-metabolic milieu (but not necessarily glucose dysmetabolism per se.) of type-2 diabetes putatively predisposes to the presumably-dysimmune intravenous immunoglobulin-G-responsive polyneuropathy. In some of our patients, especially ones having a strong type-2 diabetes genetic background, the intravenous immunoglobulin-G-responsive neuropathy preceded the diagnosis of type-2 diabetes by 5-10 years. Accordingly, Chronic Immune Dysschwannian/Dysneuronal Polyneuropathy patients having a strong type-2 diabetes genetic background are designated "genetico-diabetoid-2 neuropathy" prior to their manifesting type-2 diabetes. Intravenous immunoglobulin-G is herein suggested as a treatment for Severe Acute Respiratory Syndrome, a recent, and feared-repetitive, pandemic with many fatalities caused by a highly-contagious mutant coronavirus, for which there is no definitive treatment. Intravenous immunoglobulin-G might: a) combat a dysimmune component of Severe Acute Respiratory Syndrome, including the reactive cytokine-chemokine storm against respiratory tissues; b) contain some antibodies effective against the coronavirus non-specific components of Severe Acute Respiratory Syndrome; c) block host-cell receptors for the virus; and d) counteract secondary infections.


title: Regulation of N-glycolylneuraminic acid biosynthesis in developing pig small intestine.

text: N -Glycolylneuraminic acid (Neu5Gc), an abundant sialic acid in animal glycoconjugates, is formed by the enzyme CMP-N-acetylneuraminic acid (CMP-Neu5Ac) hydroxylase. The amount of Neu5Gc relative to other sialic acids is highly dependent on the species, tissue and developmental stage. Although the activity of the hydroxylase is a key factor in controlling Neu5Gc incorporation in adult animals, little is known about the regulation of hydroxylase expression and the role of this enzyme in determining changes in Neu5Gc during development. Using pig small intestine as a model system, the appearance of total sialic acid and the regulation of Neu5Gc biosynthesis during development were studied in various regions of this tissue. The amount of total sialic acid and Neu5Gc declined markedly in 2 weeks after birth. Although in subsequent developmental phases there were no positional differences in total sialic acid, a significant proximal-to-distal increase in Neu5Gc was detected. In all cases, a good correlation between the amount of Neu5Gc, the activity of the hydroxylase and the level of hydroxylase mRNA was observed. However, Western-blot analysis revealed considerable accumulation of less active enzyme in the post partum period, which persisted until adulthood. No evidence for cytosolic factors influencing the hydroxylase activity or for the formation of truncated enzyme was found, raising the possibility that other regulatory mechanisms are involved. The relevance of these results in the formation of Neu5Gc as a receptor for certain pig enteric pathogens is also discussed.


COVID-19 Supply Chain Considerations for Prescription Drugs in Dermatology.


title: CD13/aminopeptidase N, a novel chemoattractant for T lymphocytes in pulmonary sarcoidosis.

text: CD13/aminopeptidase N (E.C.3.4.11.2) is an ectoenzyme located in the outer membrane of a variety of cells. Because aminopeptidase expression was shown to be upregulated by a Th1-related cytokine, IFN-gamma, we examined here the significance of CD13/aminopeptidase N in pulmonary sarcoidosis. The activity of aminopeptidase in bronchoalveolar lavage fluid (BALF) was significantly higher in patients with sarcoidosis than in normal volunteers (NV) and control patients (CP). The activity significantly correlated with lymphocyte percentages and the ratio of CD4+ to CD8+ T lymphocytes in the BALF, and was higher in patients with sarcoidosis with parenchymal involvement than in those without the involvement. CD13/aminopeptidase N protein, which has a molecular mass of approximately 150 kD, was detectable in alveolar macrophages (AM) from patients with sarcoidosis at higher levels than in those from NV. CD13/aminopeptidase N induced in vitro chemotactic migration of human lymphocytes in a concentration range of 10(-)(5) to 10(-)(1) U/ml. The chemotactic activity was greater for CD4+ T lymphocytes than for CD8+ T lymphocytes. The enzymatic activity of CD13/aminopeptidase N was responsible for the chemotactic activity because bestatin, an inhibitor of CD13/aminopeptidase N, abolished the chemotactic activity. Higher chemotactic activity for lymphocytes was detected in the BALF from patients with sarcoidosis than in that from NV, and the activity was significantly decreased by treatment with bestatin. This study indicates that CD13/ aminopeptidase N expressed in AM may have a role in T-lymphocyte involvement in the sarcoid lung and the pathogenesis of alveolitis in this disorder.


title: Recent animal disease outbreaks and their impact on human populations.

text: Over the past 20 years, headlines have documented an increasing number of emerging diseases; most have an animal source (zoonoses). Recent examples include West Nile virus, severe acute respiratory syndrome (SARS), avian influenza, and monkeypox. While some emerging diseases occur among both humans and animals, others affect only animals or only humans. Nevertheless, all these new or reemerging infections have societal implications, often tied to local and national economies. It is important to understand the implications of emerging animal diseases and encourage stronger collaboration of veterinary and medical practitioners, especially in rural areas. Illnesses in agricultural workers may be the index cases for newly emerging diseases.


title: Progress with enhancing veterinary surveillance in the United Kingdom.

text: The UK has experienced various animal health events that have had national impact in recent years. In response, a ;Veterinary Surveillance Strategy' (VSS) was published in 2003, with the objective of enhancing and coordinating national veterinary surveillance practice in a way that would enable important animal health events to be detected and assessed more rapidly and reliably. The VSS adopts an integrated UK-wide approach, which includes widespread engagement with interested parties both within government and beyond. It proposes enhancing surveillance through improved collaboration; transparent and defensible prioritisation of government resources to surveillance; deriving better value from existing resources, and assuring quality of the surveillance reports and source data. This article describes progress with implementing the VSS, in particular the methodology for developing a functional network and creating an effective, quality-assured, information management system, RADAR.


title: Protein structure prediction in structure based drug design.

text: The human genome and other genome sequencing projects have generated huge amounts of protein sequence information. Recently, a structural genomics project that aims to determine at least one representative three-dimensional structure from every protein family experimentally has been started. Homology modeling will play an essential role in structure based drug design such as in silico screening; because based on these representative structures the three-dimensional structures of the remaining proteins encoded in the various genomes can be predicted by homology modeling. The results of the last Critical Assessment of Techniques for Protein Structure Prediction (CASP5) demonstrated that the quality of homology modeling prediction has improved; reaching a level of reliability that biologists can now confidently use homology modeling. With improvements in modeling software and the growing number of known protein structures, homology modeling is becoming a more and more powerful and reliable tool. The present paper discusses the features and roles of homology modeling in structure based drug design, and describes the CHIMERA and FAMS modeling systems as examples. For a sample application, homology modeling of non-structural proteins of the severe acute respiratory syndrome (SARS) coronavirus is discussed. Many biological functions involve formation of protein-protein complexes; in which the protein molecules behave dynamically in the course of binding. Therefore, an understanding of protein-protein interaction will be very important for structure based drug design. To this end, normal mode analysis is useful. The present paper discusses the prediction of protein-protein interaction using normal mode analysis and examples of applications are given.


COVID-19 and gastrointestinal endoscopy in Belgium : uncertainty and ambiguity.


title: Gastrodin prevents steroid-induced osteonecrosis of the femoral head in rats by anti-apoptosis.

text: BACKGROUND Gastrodin, as one of the major components extracted from the Chinese herb Gastrodia elata Bl., has many biologic effects, one of which is anti-apoptosis. Apoptosis is considered to be one of the pathogenetic mechanisms in steroid-induced osteonecrosis of the femoral head (ONFH). Therefore, we performed this study to investigate whether gastrodin has the potential to prevent steroid-induced ONFH. METHODS All 18 male adult Wistar rats were divided equally into three groups: the steroid group, the gastrodin+steroid group, and the control group. Osteonecrosis was induced by low-dose lipopolysaccharide and subsequent high-dose methylprednisolone. Histomorphometric method was used to determine the incidence of osteonecrosis. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay was performed to detect apoptotic index of osteocytes and osteoblasts. Real-time PCR and Western blotting were performed to detect mRNA and protein expression of Bax, Bcl-2, and Caspase-3. Fisher's exact probability test and one-way analysis of variance (ANOVA) with Turkey's post hoc test were used to examine significant differences between groups. RESULTS The incidence of osteonecrosis in the gastrodin+steroid group (16.7%) was significantly lower than that in the steroid group (83.3%). According to TUNEL assay, the apoptotic indices in the steroid group, the gastrodin+steroid group, and the control group were 91.1%, 27.1%, and 5.4%, respectively, and the differences were significant between groups. Compared with the control group and the gastrodin+steroid group, the mRNA and protein expression levels of Bax and Caspase-3 were significantly higher in the steroid group, but the Bcl-2 mRNA and protein expression levels were significantly lower. CONCLUSION Gastrodin could prevent steroid-induced ONFH by anti-apoptosis.


title: Categorization of North American porcine reproductive and respiratory syndrome viruses: epitopic profiles of the N, M, GP5 and GP3 proteins and susceptibility to neutralization.

text: Eleven epitopes were identified by murine monoclonal antibodies (MAbs) that represented the N, M, GP5 and GP3 proteins of the North American (NA) porcine reproductive and respiratory syndrome (PRRS) virus, KY 35 (NVSL 46907). Three discontinuous epitopes of the N and M proteins were designated EpORF7-Fd through Hd and EpORF6-Ad through Cd. Five continuous epitopes of the GP5 and GP3 proteins were designated EpORF5-A through C and EpORF3-A and B. The MAbs representing EpORF5-C and EpORF6-A and B had neutralizing activity. The MAbs representing the above epitopes, except EpORF7-Gd and Hd, expanded the virus marker system described in a previous study in which a panel of 69 NA viruses and the Lelystad virus were categorized into 5 antigenic groups, I15 through V15 based on the presence or absence of 5 continuous epitopes of the N protein. Antigenic groups I15 and II15, which represented 84.7 and 11.6% of all viruses tested, were categorized further into 9 and 4 subgroups, respectively. The remaining NA viruses and the Lelystad virus were distributed among 4 groups, one of which was represented by 2 subgroups. Significant (P<0.05) differences in sensitivity to neutralization of 28 viruses representing 6 antigenic groups by the 3 neutralizing MAbs suggested that sensitivity to neutralization may also be of value in categorizing PRRS viruses.


title: History of the First-Generation Marek's Disease Vaccines: The Science and Little-Known Facts.

text: Shortly after the isolation of Marek's disease (MD) herpesvirus (MDV) in the late 1960s vaccines were developed in England, the United States, and The Netherlands. Biggs and associates at the Houghton Poultry Research Station (HPRS) in England attenuated HPRS-16, the first cell-culture-isolated MDV strain, by passaging HPRS-16 in chick kidney cells. Although HPRS-16/Att was the first commercially available vaccine, it never became widely used and was soon replaced by the FC126 strain of herpesvirus of turkeys (HVT) vaccine developed by Witter and associates at the Regional Poultry Research Laboratory (now Avian Disease and Oncology Laboratory [ADOL]) in East Lansing, MI. Ironically, Kawamura et al. isolated a herpesvirus from kidney cell cultures from turkeys in 1969 but never realized its potential as a vaccine against MD. Rispens of the Central Veterinary Institute (CVI) developed the third vaccine. His associate, Maas, had found commercial flocks of chickens with MDV antibodies but without MD. Subsequently, Rispens isolated a very low pathogenic strain from hen number 988 from his MD antibody-positive flock, which was free of avian leukosis virus and clinical MD. This isolate became the CVI-988 vaccine used mostly in The Netherlands. During the late 1970s, HVT was no longer fully protective against some new emerging field strains. The addition of SB-1, isolated by Schat and Calnek, to HVT improved protection against the emerging very virulent strains. In the 1990s CVI-988 became the worldwide vaccine gold standard. This review will present data from published papers and personal communications providing additional information about the exciting 15-yr period after the isolation of MDV to the development of the different vaccines.


title: New developments in the search for the etiologic agent of Kawasaki disease.

text: PURPOSE OF REVIEW The aim of this article is to review recent developments in the search for the etiologic agent of Kawasaki disease. RECENT FINDINGS Two recently proposed theories of Kawasaki disease etiology, the toxic shock syndrome toxin-1 hypothesis and the coronavirus NL-63 hypothesis, have been studied extensively and have been disproven. Surprisingly, IgA plasma cells infiltrate inflamed tissues in acute Kawasaki disease, including the coronary artery, and are oligoclonal, or antigen-driven. Synthetic versions of predominant IgA antibodies in acute Kawasaki disease arterial tissue bind to an antigen present in acute Kawasaki disease ciliated bronchial epithelium and in a subset of macrophages in acute inflamed Kawasaki disease tissues. Light and electron microscopic studies of the antigen in acute Kawasaki disease ciliated bronchial epithelium indicate that the Kawasaki disease-associated antigen localizes to cytoplasmic inclusion bodies that are consistent with aggregates of viral protein and associated nucleic acid. SUMMARY The identification of cytoplasmic inclusion bodies in acute Kawasaki disease ciliated bronchial epithelium has provided direction for future Kawasaki disease etiology studies. Transmission electron microscopic examination of glutaraldehyde-fixed medium-sized bronchi from acute Kawasaki disease fatalities and analysis of the protein and nucleic acid components of the inclusions should provide important information about these inclusion bodies and speed the identification of the specific etiologic agent of Kawasaki disease.


title: Spontaneous breathing trial and post-extubation work of breathing in morbidly obese critically ill patients.

text: BACKGROUND Predicting whether an obese critically ill patient can be successfully extubated may be specially challenging. Several weaning tests have been described but no physiological study has evaluated the weaning test that would best reflect the post-extubation inspiratory effort. METHODS This was a physiological randomized crossover study in a medical and surgical single-center Intensive Care Unit, in patients with body mass index (BMI) >35 kg/m2 who were mechanically ventilated for more than 24 h and underwent a weaning test. After randomization, 17 patients were explored using five settings : pressure support ventilation (PSV) 7 and positive end-expiratory pressure (PEEP) 7 cmH2O; PSV 0 and PEEP 7cmH2O; PSV 7 and PEEP 0 cmH2O; PSV 0 and PEEP 0 cmH2O; and a T piece, and after extubation. To further minimize interaction between each setting, a period of baseline ventilation was performed between each step of the study. We hypothesized that the post-extubation work of breathing (WOB) would be similar to the T-tube WOB. RESULTS Respiratory variables and esophageal and gastric pressure were recorded. Inspiratory muscle effort was calculated as the esophageal and trans-diaphragmatic pressure time products and WOB. Sixteen obese patients (BMI 44 kg/m2 ± 8) were included and successfully extubated. Post-extubation inspiratory effort, calculated by WOB, was 1.56 J/L ± 0.50, not statistically different from the T piece (1.57 J/L ± 0.56) or PSV 0 and PEEP 0 cmH2O (1.58 J/L ± 0.57), whatever the index of inspiratory effort. The three tests that maintained pressure support statistically underestimated post-extubation inspiratory effort (WOB 0.69 J/L ± 0.31, 1.15 J/L ± 0.39 and 1.09 J/L ± 0.49, respectively, p < 0.001). Respiratory mechanics and arterial blood gases did not differ between the five tests and the post-extubation condition. CONCLUSIONS In obese patients, inspiratory effort measured during weaning tests with either a T-piece or a PSV 0 and PEEP 0 was not different to post-extubation inspiratory effort. In contrast, weaning tests with positive pressure overestimated post-extubation inspiratory effort. TRIAL REGISTRATION Clinical trial.gov (reference NCT01616901 ), 2012, June 4th.


title: Identification and containment of an outbreak of SARS in a community hospital.

text: BACKGROUND Severe acute respiratory syndrome (SARS) is continuing to spread around the world. All hospitals must be prepared to care for patients with SARS. Thus, it is important to understand the transmission of this disease in hospitals and to evaluate methods for its containment in health care institutions. We describe how we cared for the first 2 patients with SARS admitted to our 419-bed community hospital in Richmond Hill, Ont., and the response to a SARS outbreak within our institution. METHODS We collected clinical and epidemiological data about patients and health care workers at our institution who during a 13-day period had a potential unprotected exposure to 2 patients whose signs and symptoms were subsequently identified as meeting the case definition for probable SARS. The index case at our hospital was a patient who was transferred to our intensive care unit (ICU) from a referral hospital on Mar. 16, 2003, where he had been in close proximity to the son of the individual with the first reported case of SARS in Toronto. After 13 days in the ICU, a diagnosis of probable SARS was reached for our index case. Immediately upon diagnosis of our index case, respiratory isolation and barrier precautions were instituted throughout our hospital and maintained for a period of 10 days, which is the estimated maximum incubation period reported for this disease. Aggressive surveillance measures among hospital staff, patients and visitors were also maintained during this time. RESULTS During the surveillance period, 15 individuals (10 hospital staff, 3 patients and 2 visitors) were identified as meeting the case definition for probable or suspected SARS, in addition to our index case. All but 1 individual had had direct contact with a symptomatic patient with SARS during the period of unprotected exposure. No additional cases were identified after infection control precautions had been implemented for 8 days. No cases of secondary transmission were identified in the 21 days following the implementation of these precautions at our institution. INTERPRETATION SARS can easily be spread by direct personal contact in the hospital setting. We found that the implementation of aggressive infection control measures is effective in preventing further transmission of this disease.


Viruses in water.


The animal story.


title: Clinical and imaging findings in patients with severe acute respiratory syndrome.

text: OBJECTIVE To investigate the clinical and imaging characteristics of severe acute respiratory syndrome (SARS), and to study their relationship. METHODS Forty-six SARS confirmed patients were admitted to our hospital from February to April, 2003. X-ray examination documents were available in all cases and chest CT scanning was acquired in 6 cases, which were analyzed retrospectively, accompanied by their clinical features. RESULTS Fever was found in 97.8% of the patients. Clinical symptoms were mild, but X-ray and CT findings were distinct. CT scanning demonstrated ground glass like lesions and large patchy exudation and consolidation at the early stage in 6 cases. Different findings on radiography and CT were related to the different phases of the disease. After treatment, most lesions were absorbed completely, but slowly in patients with multi-lobe consolidation and/or extensive interstitial infiltration. CONCLUSION Special clinical and imaging findings could be found in SARS cases. The prognosis of SARS patients is related to the degree of lesions detected by radiography and CT.


title: Clipping of previously coiled cerebral aneurysms: efficacy, safety, and predictors in a cohort of 111 patients.

text: OBJECTIVE With the increasing number of aneurysms treated with endovascular coiling, more recurrences are being encountered. The aim of this study was to evaluate the efficacy and safety of microsurgical clipping in the treatment of recurrent, previously coiled cerebral aneurysms and to identify risk factors that can affect the outcomes of this procedure. METHODS One hundred eleven patients with recurrent aneurysms whose lesions were managed by surgical clipping between January 2002 and October 2014 were identified. The rates of aneurysm occlusion, retreatment, complications, and good clinical outcome were retrospectively determined. Univariate and multivariate logistic regressions were performed to identify factors associated with these outcomes. RESULTS The mean patient age was 50.5 years, the mean aneurysm size was 7 mm, and 97.3% of aneurysms were located in the anterior circulation. The mean follow-up was 22 months. Complete aneurysm occlusion, as assessed by intraoperative angiography, was achieved in 97.3% of aneurysms (108 of 111 patients). Among patients, 1.8% (2 of 111 patients) had a recurrence after clipping. Retreatment was required in 4.5% of patients (5 of 111) after clipping. Major complications were observed in 8% of patients and mortality in 2.7%. Ninety percent of patients had a good clinical outcome. Aneurysm size (OR 1.4, 95% CI 1.08-1.7; p = 0.009) and location in the posterior circulation were significantly associated with higher complications. All 3 patients who had coil extraction experienced a postoperative stroke. Aneurysm size (OR 1.2, 95% CI 1.02-1.45; p = 0.025) and higher number of interventions prior to clipping (OR 5.3, 95% CI 1.3-21.4; p = 0.019) were significant predictors of poor outcome. An aneurysm size > 7 mm was a significant predictor of incomplete obliteration and retreatment (p = 0.018). CONCLUSIONS Surgical clipping is safe and effective in treating recurrent, previously coiled cerebral aneurysms. Aneurysm size, location, and number of previous coiling procedures are important factors to consider in the management of these aneurysms.


title: Fatal ulcerative and hemorrhagic typhlocolitis in a pregnant heifer associated with natural bovine enterovirus type-1 infection.

text: One 2-year-old, 7.5 months pregnant Aberdeen Angus out of a herd of 100 apparently healthy cows, died within 10 hours of hospitalization. At necropsy, multiple foci of mucosal hemorrhage and ulceration were observed in the spiral colon and cecum. Virus isolation from intestinal lesions yielded a cytopathic virus, which was revealed by electron microscopy to be an approximately 27 nm, nonenveloped virus. Further characterization by reverse transcription-polymerase chain reaction (RT-PCR), sequencing of the 5'UTR and partial VP1 coding region, and phylogenetic analysis classified the virus isolate as bovine enterovirus type 1 (BEV-1). No other significant pathogens were detected. This is the first report of BEV-1 isolated in the USA from an animal with fatal enteric disease in more than 20 years. Further investigation is required to determine the prevalence of BEV in North America and to establish the clinical relevance of this understudied virus.


Tears and conjunctival scrapings for coronavirus in patients with SARS.


title: Studies on the structure of a coronavirus-avian infectious bronchitis virus.

text: When avian infectious bronchitis virus (IBV) is fixed in formaldehyde, negative stain is able to penetrate the particle and an internal component is visualized. This component is seen as a tongue or flask shaped structure attached at one point to the outer virus membrane. A model yielding transmission patterns similar to the virus has been made. Gradient centrifugation studies on IBV reveal that the RNP is associated with the internal sac.


Model improvement via data assimilation toward ecological forecasting.


title: Replicating success: developing a standard FETP curriculum.

text: Field epidemiology training programs have been successful models to address a country's needs for a skilled public health workforce, partly due to their responsiveness to the countries' unique needs. The Centers for Disease Control and Prevention has partnered with ministries of health to strengthen their workforce through customized competency-based training programs. While desirable, emphasis on program flexibility can result in redundancy and inconsistency. To address this challenge, the ADDIE model (analysis, design, development, implementation, and evaluation) of instructional design was used by a cross-functional team to guide completion of a standard curriculum based on 15 competencies. The standard curriculum has supported the development and expansion of programs while still allowing for adaptation. This article describes the process that was used to develop the curriculum, which, together with needs assessment and evaluation, is crucial for successful training programs.


title: Calculated Decisions: Brescia-COVID Respiratory Severity Scale (BCRSS)/Algorithm.

text: The Brescia-COVID respiratory severity scale/algorithm is a stepwise management approach to COVID-19 patients based on clinical severity. The BCRSS was rapidly developed in Brescia, Italy, during that nation's COVID-19 crisis. The scale has not been validated or tested in other populations. The BCRSS uses patient examination features along with the need for escalating levels of respiratory support (NIV, intubation, proning) to suggest treatment recommendations. The scale simplifies the clinical summary of a patient's status, and allows clinicians to compare patients to one another and to track the trend of a patient's level of respiratory severity over time.


title: Functional characterization of XendoU, the endoribonuclease involved in small nucleolar RNA biosynthesis.

text: XendoU is the endoribonuclease involved in the biosynthesis of a specific subclass of Xenopus laevis intron-encoded small nucleolar RNAs. XendoU has no homology to any known cellular RNase, although it has sequence similarity with proteins tentatively annotated as serine proteases. It has been recently shown that XendoU represents the cellular counterpart of a nidovirus replicative endoribonuclease (NendoU), which plays a critical role in viral replication and transcription. In this paper, we combined prediction and experimental data to define the amino acid residues directly involved in XendoU catalysis. Specifically, we find that XendoU residues Glu-161, Glu-167, His-162, His-178, and Lys-224 are essential for RNA cleavage, which occurs in the presence of manganese ions. Furthermore, we identified the RNA sequence required for XendoU binding and showed that the formation of XendoU-RNA complex is Mn2+-independent.


General information on the vertebrate virus data bank 'DAISY': first report.


title: Depression and anxiety in epilepsy: the association with demographic and seizure-related variables.

text: BACKGROUND Depression and anxiety are common psychiatric symptoms in patients with epilepsy, exerting a profound negative effect on health-related quality of life. Several issues, however, pertaining to their association with psychosocial, seizure-related and medication factors, remain controversial. Accordingly, the present study was designed to investigate the association of interictal mood disorders with various demographic and seizure-related variables in patients with newly-diagnosed and chronic epilepsy. METHODS We investigated 201 patients with epilepsy (51.2% males, mean age 33.2 +/- 10.0 years, range 16-60) with a mean disease duration of 13.9 +/- 9.5 years. Depression and anxiety were assessed in the interictal state with the Beck Depression Inventory, 21-item version (BDI-21) and the state and trait subscales of the State-Trait Anxiety Inventory (STAI-S and STAI-T), respectively. The association of mood disorders with various variables was investigated with simple and multiple linear regression analyses. RESULTS High seizure frequency and symptomatic focal epilepsy (SFE) were independent determinants of depression, together accounting for 12.4% of the variation of the BDI-21. The STAI-S index was significantly associated with the type of epilepsy syndrome (SFE). Finally, high seizure frequency, SFE and female gender were independent determinants of trait anxiety accounting for 14.7% of the variation of the STAI-T. CONCLUSION Our results confirm the prevailing view that depression and anxiety are common psychological disorders in epileptics. It is additionally concluded that female gender, high seizure frequency and a symptomatic epilepsy syndrome are independent risk factors for the development of anxiety and/or depression.


title: [The application of indirect immuno-fluorescence assay in the diagnosis of severe acute respiratory syndrome].

text: OBJECTIVE To explore the temporal profile of serum antibody against coronavirus in patients with severe acute respiratory syndrome (SARS), and to evaluate the reliability of indirect immuno-fluorescence assay (IFA) in the diagnosis of SARS. METHODS Clinically confirmed SARS patients, suspected SARS patients, and controls were included in the study. IFA was used to detect the serum antibody against SARS coronavirus. General information about the subjects was collected using a standard questionnaire. RESULTS The positive rates of specific IgG and IgM against SARS virus within 10 days after onset of the disease were 55.1% and 16.3% respectively and then increased up to 89.8% for IgG and 65.3% for IgM. After 25 days of the onset of the disease, 90.9% patients became positive for both IgG and IgM. Results from chi-square for trend test revealed that the positive rates of both IgG and IgM increased with time (chi(2) for trend = 16.376, P = 0.00005 for IgG; chi(2) for trend = 28.736, P = 0.00000 for IgM). Sensitivity, specificity and agreement value of IFA regarding the diagnosis of SARS were all higher than 90%. CONCLUSION IFA can be used to assist diagnosis of SARS after 10 days of the onset of disease.


title: Prospective case-control study of role of infection in patients who reconsult after initial antibiotic treatment for lower respiratory tract infection in primary care.

text: OBJECTIVE To assess direct and indirect evidence of active infection which may benefit from further antibiotics in adults who reconsult within 4 weeks of initial antibiotic management of acute lower respiratory tract infection in primary care. DESIGN Observational study with a nested case-control group. SETTING Two suburban general practices in Arnold, Nottingham, over 7 winter months. SUBJECTS 367 adults aged 16 years and over fulfilling a definition of lower respiratory tract infection and treated with antibiotics. 74 (20%) patients who reconsulted within 4 weeks for the same symptoms and 82 "control" patients who did not were investigated in detail at fallow up. MAIN OUTCOME MEASURES Direct and indirect evidence of active infection at the time of the reconsultation or the follow up visit with the research nurse for the controls. Investigations performed included sputum culture, pneumococcal antigen detection, serial serology for viral and atypical pathogens and C reactive protein, throat swabs for detecting viral and atypical pathogens by culture and polymerase chain reaction, and chest radiographs. RESULTS Demographic and clinical features of the groups were similar. Two thirds of the 74 patients who reconsulted received another antibiotic because the general practitioner suspected continuing infection. Any evidence of infection warranting antibiotic treatment was uncommon at reconsultation. The findings for the two groups were similar for the occurrence of identified pathogens; chest x ray changes of infection (present in 13%); and C reactive protein concentrations, which had nearly all fallen towards normal. Only three patients in the reconsultation group had concentrations > or = 40 mg/l. Pathogens identified at follow up in the 156 patients in both groups included ampicillin sensitive bacteria in six. Atypical infections diagnosed in 27 (Chlamydia pneumoniae in 22) and viral infections in 54 had probably been present at the initial presentation. CONCLUSION Our study suggests that active infection, which may benefit from further antibiotics, is uncommon in patients who reconsult after a lower respiratory tract infection, and a repeat antibiotic prescription should be the exception rather than the rule. Other factors, such as patients' perception of their illness, may be more important than disease and infection in their decision to reconsult.


title: Recombinant mouse hepatitis virus strain A59 from cloned, full-length cDNA replicates to high titers in vitro and is fully pathogenic in vivo.

text: Mouse hepatitis virus (MHV) is the prototype of group II coronaviruses and one of the most extensively studied coronaviruses. Here, we describe a reverse genetic system for MHV (strain A59) based upon the cloning of a full-length genomic cDNA in vaccinia virus. We show that the recombinant virus generated from cloned cDNA replicates to the same titers as the parental virus in cell culture ( approximately 10(9) PFU/ml), has the same plaque morphology, and produces the same amounts and proportions of genomic and subgenomic mRNAs in virus-infected cells. In a mouse model of neurological infection, the recombinant and parental viruses are equally virulent, they replicate to the same titers in brain and liver, and they induce similar patterns of acute hepatitis, acute meningoencephalitis, and chronic demyelination. We also describe improvements in the use of the coronavirus reverse genetic system based on vaccinia virus cloning vectors. These modifications facilitate (i) the mutagenesis of cloned cDNA by using vaccinia virus-mediated homologous recombination and (ii) the rescue of recombinant coronaviruses by using a stable nucleocapsid protein-expressing cell line for the electroporation of infectious full-length genomes. Thus, our system represents a versatile and universal tool to study all aspects of MHV molecular biology and pathogenesis. We expect this system to provide valuable insights into the replication of group II coronaviruses that may lead to the development of novel strategies against coronavirus infections, including the related severe acute respiratory syndrome coronavirus.


title: Pandemic and public health controls: toward an equitable compensation system.

text: There is increasing global concern about the potential impact of pandemic infections, including influenza, SARS and bioterrorist attacks involving infectious diseases. Many countries have prepared plans for responding to a major pandemic. In Australia, the Federal and State pandemic plans include measures such as contact tracing, ensuring availability of antimicrobials, quarantine and social distancing. Many of these measures would involve severe restrictions on individual citizens and small businesses. Issues of compensation for cooperation and compliance with pandemic plans need to be addressed in policy discussion. The instrumental benefits of compensation in the event of a pandemic have not been sufficiently recognised. Greater attention paid now to mechanisms to compensate individual and business costs associated with compliance would increase trust in government pandemic plans, encourage compliance and reduce the health and economic impact of a pandemic.


Research and Ethics during the COVID-19 Pandemic.


title: Extubation of the difficult airway.

text: Managing the airway in the intensive care unit (ICU) is complicated by a wide array of physiologic factors. Difficult airway may be a consequence of patient’s anatomy or airway edema developed during the ICU stay and mechanical ventilation. The incidence of failed airways and of cardiac arrest related to airway instrumentation in the ICU is much higher than that of elective intubations performed in the operating room. In this article, we will provide a framework for identifying a difficult airway, criteria for safe extubation, as well as review the devices that are available for airway management in the ICU. Proficiency in identifying a potentially difficult airway and thorough familiarity with strategies and techniques of securing the airway are necessary for safe practice of critical care medicine


title: Influenza virus matrix protein is the major driving force in virus budding.

text: To get insights into the role played by each of the influenza A virus polypeptides in morphogenesis and virus particle assembly, the generation of virus-like particles (VLPs) has been examined in COS-1 cell cultures expressing, from recombinant plasmids, different combinations of the viral structural proteins. The presence of VLPs was examined biochemically, following centrifugation of the supernatants collected from transfected cells through sucrose cushions and immunoblotting, and by electron-microscopic analysis. It is demonstrated that the matrix (M1) protein is the only viral component which is essential for VLP formation and that the viral ribonucleoproteins are not required for virus particle formation. It is also shown that the M1 protein, when expressed alone, assembles into virus-like budding particles, which are released in the culture medium, and that the recombinant M1 protein accumulates intracellularly, forming tubular structures. All these results are discussed with regard to the roles played by the virus polypeptides during virus assembly.


title: Binding of transmissible gastroenteritis coronavirus to cell surface sialoglycoproteins.

text: The surface glycoprotein S of transmissible gastroenteritis virus (TGEV) has two binding activities. (i) Binding to porcine aminopeptidase N (pAPN) is essential for the initiation of infection. (ii) Binding to sialic acid residues on glycoproteins is dispensable for the infection of cultured cells but is required for enteropathogenicity. By comparing parental TGEV with mutant viruses deficient in the sialic acid binding activity, we determined the contributions of both binding activities to the attachment of TGEV to cultured cells. In the presence of a functional sialic acid binding activity, the amount of virus bound to two different porcine cell lines was increased sixfold compared to the binding of the mutant viruses. The attachment of parental virus was reduced to levels observed with the mutants when sialic acid containing inhibitors was present or when the cells were pretreated with neuraminidase. In virus overlay binding assays with immobilized cell surface proteins, the mutant virus only recognized pAPN. In addition, the parental virus bound to a high-molecular-mass sialoglycoprotein. The recognition of pAPN was sensitive to reducing conditions and was not dependent on sialic acid residues. On the other hand, binding to the sialic acid residues of the high-molecular-mass glycoprotein was observed regardless of whether the cellular proteins had been separated under reducing or nonreducing conditions. We propose that binding to a surface sialoglycoprotein is required for TGEV as a primary attachment site to initiate infection of intestinal cells. This concept is discussed in the context of other viruses that use two different receptors to infect cells.


title: A randomized, controlled clinical pilot study comparing three types of compression therapy to treat venous leg ulcers in patients with superficial and/or segmental deep venous reflux .

text: Compression therapy--including inelastic, elastic, and intermittent pneumatic compression--is the standard of care for venous ulcers (VLUs) and chronic venous insufficiency, but there is no consensus in the literature regarding the most effective type of compression therapy. A prospective, randomized, clinical pilot study was conducted among 70 patients with unilateral VLUs treated in a hospital dermatology department in Poland to compare three types of compression therapy (intermittent pneumatic compression, stockings, and short-stretch bandages) in persons with superficial deep venous reflux alone or combined with the segmental variety. Study endpoints were change in ulcer dimensions and proportions healed. Patients with superficial or combined superficial and deep vein insufficiency were randomly allocated to receive one of the three therapies (one of each vein type for each treatment option, six groups total). All patients received saline-soaked gauze dressings along with micronized purified flavonoid fraction, diosmin, hesperidin, and Daflon 500 once daily. Compression treatments were changed or pneumatic compression provided daily for 15 days. Wound size reduction and percentage of wounds healed were significantly higher in groups receiving intermittent pneumatic compression or stockings than in groups using short-stretch bandages (for percentage change of ulcer surface area, P = 0.02; for healing rates P = 0.01). These results warrant additional randomized controlled clinical studies with a larger sample size and longer patient follow-up.


Antiemesis clinical practice guidelines in oncology.


Use of healthcare worker sickness absenteeism surveillance as a potential early warning system for influenza epidemics in acute care hospitals.


title: Hatchery Spray Cabinet Administration Does Not Damage Avian Coronavirus Infectious Bronchitis Virus Vaccine Based on Analysis by Electron Microscopy and Virus Titration.

text: studies in our laboratory showed that the Arkansas-Delmarva Poultry Industry (Ark-DPI) vaccine given to 1-day-old chickens by hatchery spray cabinet replicated poorly and failed to adequately protect broilers against homologous virus challenge, whereas the same vaccine given by eye-drop did replicate and the birds were protected following homologous virus challenge. To determine if mechanical damage following spray application plays a role in failure of the Ark-DPI vaccine, we examined the morphology of three Ark-DPI vaccines from different manufacturers using an electron microscope and included a Massachusetts (Mass) vaccine as control. One of the Ark-DPI vaccines (vaccine A) and the Mass vaccine had significantly (P < 0.005) fewer spikes than the other two Ark-DPI vaccines. We also found that the Ark-DPI and Mass vaccines had significantly (P < 0.005) fewer spike proteins per virus particle when compared to their respective challenge viruses. This observation is interesting and may provide some insight into the mechanism behind infectious bronchitis virus attenuation. No obvious differences were observed in virus morphology and no consistent trend in the number of spikes per virion was found in before- and after-spray samples. We also determined the vaccine titer before and after spray in embryonated eggs and found that both Ark-DPI and Mass vaccines had a similar drop in titer, 0.40 logi and 0.310 logi, respec10ively. Based on these data, it appears that mechanical damage to the Ark-DPI vaccine is not occurring when delivered by a hatchery spray cabinet, suggesting that some other factor is contributing to the failure of that vaccine when given by that method.


title: Ranpirnase: amphibian ribonuclease A, P-30 protein-alfacell.

text: Ranpirnase [Onconase] is an amphibian oocyte/early embryo ribonuclease (RNase) of 105 amino acids in length that is capable of controlling tumour growth by degrading RNA within cancer cells, resulting in inhibition of protein synthesis and arresting mitosis in G(1 )phase. It represents the first successful isolation, purification and characterisation of the oocytic/early embryonic factor that is capable of controlling cell growth activities of the early embryonic tissues. Alfacell Corporation is currently conducting clinical trials of ranpirnase in patients with unresectable malignant mesothelioma and non-small-cell lung cancer. The company may initiate phase II clinical trials in breast cancer and oesophageal cancer in 2006. Alfacell expanded a research agreement with the National Cancer Institute in September 2002, allowing the NCI to examine the effects of ranpirnase as a radiation enhancer. However, investigation in this use of ranpirnase now appears to be discontinued. Alfacell is conducting a confirmatory phase IIIb registration trial of ranpirnase plus doxorubicin versus doxorubicin alone in more than 360 patients with unresectable malignant mesothelioma, and will assess survival as the primary endpoint. The targeted treatment group in this trial represents 90% of malignant mesothelioma patients at the time of diagnosis. The trial is being conducted in the US, Canada, Poland, Italy, Germany, Australia, New Zealand, Russia, Romania, Mexico and Brazil. In April 2006, a total of 210 events (patient deaths) was reached, representing two-thirds of the required events for the study. Results from the protocol-specified first interim analysis based on one-third of the required events have been reported and the company has the option to conduct a second interim analysis of the data at any point after 210 events. A final analysis will be undertaken at 316 events. Alfacell completed a phase III trial of single-agent ranpirnase in patients with unresectable malignant mesothelioma in April 1999. The efficacy of ranpirnase was compared with that of doxorubicin (head-to-head). The primary objectives were overall survival, progression-free survival and quality of life. In preclinical studies, ranpirnase demonstrated significant activity against neuroblastoma, rhabdomyosarcoma and chemotherapy-resistant variants of these cancer cells. Development for these indications has been discontinued. Preclinical investigations conducted by Alfacell showed synergistic antitumour effects between ranpirnase and proteasome inhibitors. However, development is this area has been discontinued. Alfacell announced in May 2003 that it would be providing ranpirnase to the federal severe acute respiratory syndrome (SARS) testing programme for evaluation against the human coronavirus implicated in the disease. No further development has been reported. Alfacell has received nine US and four European patents for ranpirnase. Patents issued in the US range from the 1996-issued patent (No. 5 559 212) covering the amino acid sequence of ranpirnase, to the patent (No. 6 175 003 B1) issued in January 2001 protecting the gene sequences of the compound plus another genetically engineered variant, effectively protecting the company's proprietary technology. In August 2002, Alfacell received a US patent (No. 6 423 515 B1) entitled 'Methods of Making Nucleic Acids Encoding Ribonucleases'. This patent is effective until 2020.


title: Apoptosis and T-cell depletion during feline infectious peritonitis.

text: Cats that have succumbed to feline infectious peritonitis, an immune-mediated disease caused by variants of feline coronaviruses, show apoptosis and T-cell depletion in their lymphoid organs. The ascitic fluid that develops in the course of the condition causes apoptosis in vitro but only in activated T cells. Since feline infectious peritonitis virus does not infect T cells, and viral proteins did not inhibit T-cell proliferation, we postulate that soluble mediators released during the infection cause apoptosis and T-cell depletion.


title: The enigma of double-stranded RNA (dsRNA) associated with mushroom virus X (MVX).

text: New variants of pathogenic fungal viruses are emerging and they are enigmatic in revealing their molecular identity and of their origin. Double-stranded RNAs, some in non-encapsidated forms are increasingly becoming causal agents for sporadic diseases and are consistently associated with a complex profile of dsRNAs, presumably of (multiple) viral origin present in the host while the same are conspicuously absent in healthy (looking) counterparts. The emergence of an unusual Agaricus bisporus mushroom 'patch disease' first reported in 1996, later termed as 'mushroom virus X' (MVX), exhibited a wide range of symptoms (e.g. barren patches beside healthy looking mushrooms, arrested pins, premature opening, brown, off-colour and distortions in shape). A variable compendium of novel 26 (dsRNA) elements, ranging in sizes between 20.2kb to 0.64kb, several of them (-17/26) in non-encapsidated form have been shown to occur in the diseased mushroom fruiting bodies and are thought to comprise multiple viruses. Ten years on, this devastating disease is now more widespread and prevalent in a number of European countries (e.g. The Netherlands, Ireland) ranging from occasional to severe outbreaks leading to crop losses. Impressive data has been accumulated on the symptoms, but the potential aetiological sources, biochemical and molecular characterizations corresponding to the symptoms vis-a-vis MVX linked dsRNAs still remain either elusive or unclear. We have overviewed mainly the molecular findings of research groups working on MVX in these countries together with our own work on MVX in Northern Ireland. To date, the results reviewed suggest that with the exception of 4 low molecular weight dsRNA bands (sizes 2.0. 1.8, 0.8 and 0.6 kb) which consistently were found synchronous to mushroom off-colour/browning symptoms in the UK and The Netherlands, other individual MVX dsRNAs or their banding patterns clearly lack credible relationship with other symptoms of the MVX disease complex. The issues in the molecular characterisation of the MVX dsRNAs include the disparate results on the molecular sequences obtained for some of these by the different research groups, the varying molecular methods or approaches adopted by them for deciphering the nucleotide sequences of the novel dsRNAs that are different from previously encountered mushroom viruses. The future outlook and general consensus among mushroom researchers worldwide is for an urgent need to recruit international taskforce and re-focus on clarifying the symptom vis-a-vis dsRNAs in the enigmatic MVX disease complex. As crossing the cellular membrane is a key step to infection process, we have also attempted to draw parallels with other viruses in terms of the potential cell entry mechanisms for MVX dsRNAs. In the light of MVX disease and A. bisporus being a commercial crop worldwide in agri-food markets, and taking cue from its nearest Basidiomycete model mushroom, Coprinus cinereus whose genome mapping is completed, we also propose that it may be timely for the international research groups to renew efforts to prop up a network for sequencing the host A. bisporus mushroom genome (-38 MB) for a better understanding of host-pathogen relationships.


title: [Study on the risk factors related to severe acute respiratory syndrome among close contactors in Beijing].

text: OBJECTIVE To understand the risk factors on severe acute respiratory syndrome (SARS) among their contacts and to develop effective strategy for its control. METHODS Available epidemiological data of SARS cases and close contacts were reviewed and analyzed by SPSS. RESULTS Out of the 2195 close contacts, 138 (6.3%) were diagnosed as SARS. Among colleagues and classmates of SARS patients, the infection rate was 0.36% versus 31.71% in contacts among families and hospitals, 0.77% in schools. No one was infected among 459 close contacts to SARS in the working unit. CONCLUSIONS Among close contacts, factors that facilitating transmission would include: time, extent, frequency and place of contact to the patients, as well as factors related to close contacts as way, time of isolation and age. One of the epidemiological characteristics was that SARS were as clustered in the family among those close contacts. It is important to control the spread of SARS through supervision on the close contacts to patients.


title: Coronaviruses as vectors: stability of foreign gene expression.

text: Coronaviruses are enveloped, positive-stranded RNA viruses considered to be promising vectors for vaccine development, as (i) genes can be deleted, resulting in attenuated viruses; (ii) their tropism can be modified by manipulation of their spike protein; and (iii) heterologous genes can be expressed by simply inserting them with appropriate coronaviral transcription signals into the genome. For any live vector, genetic stability is an essential requirement. However, little is known about the genetic stability of recombinant coronaviruses expressing foreign genes. In this study, the Renilla and the firefly luciferase genes were systematically analyzed for their stability after insertion at various genomic positions in the group 1 coronavirus feline infectious peritonitis virus and in the group 2 coronavirus mouse hepatitis virus. It appeared that the two genes exhibit intrinsic differences, the Renilla gene consistently being maintained more stably than the firefly gene. This difference was not caused by genome size restrictions, by different effects of the encoded proteins, or by different consequences of the synthesis of the additional subgenomic mRNAs. The loss of expression of the firefly luciferase was found to result from various, often large deletions of the gene, probably due to RNA recombination. The extent of this process appeared to depend strongly on the coronaviral genomic background, the luciferase gene being much more stable in the feline than in the mouse coronavirus genome. It also depended significantly on the particular genomic location at which the gene was inserted. The data indicate that foreign sequences are more stably maintained when replacing nonessential coronaviral genes.


Replication of avian infectious bronchitis virus in African green monkey kidney cell line VERO.


title: Enhancement of central nervous system remyelination in immune and non-immune experimental models of demyelination.

text: Studies in both humans and experimental animals indicate that there is potential for full remyelination following CNS demyelination, but the factors that control the degree of myelin repair are unknown. In the Theiler's virus model of demyelination CNS remyelination can be promoted either by global immunosuppression or by selective immunoglobulin therapy. In this paper we discuss whether immunoglobulin-mediated remyelination is a characteristic of immune-mediated demyelination, or whether immunoglobulin-mediated remyelination also occurs in the toxic-traumatic model of lysolecithin-induced demyelination. Our data support the hypothesis that even in a non-primary immune model of demyelination, manipulating the immune system can be beneficial in myelin repair.


title: Rhinovirus infection in nonasthmatic subjects: effects on intrapulmonary airways.

text: The common cold is a highly prevalent, uncomplicated upper airway disease. However, rhinovirus (RV) infection can lead to exacerbation of asthma, with worsening in airway hyperresponsiveness and bronchial inflammation. The current authors questioned whether such involvement of the intrapulmonary airways is disease specific. Twelve nonatopic, healthy subjects (forced expiratory volume in one second (FEV1) >80% predicted, provocation concentration causing a 20% fall in FEV1 (PC20) >8 mg x mL(-1)) were experimentally infected with RV16. Next to PC20 and the maximal response to methacholine (MFEV1 and MV'40p), the numbers of mucosal inflammatory cells and epithelial intercellular adhesion molecule (ICAM)-1 expression in bronchial biopsies were assessed before and 6 days after RV16 inoculation. RV16 infection induced a small but consistent increase in maximal airway narrowing, without a change in PC20. There was a significant increase in bronchial epithelial ICAM-1 expression after RV16, whereas inflammatory cell counts did not change. Nevertheless, the change in the number of submucosal CD3+ cells was correlated with the change in MV'40p. In conclusion, rhinovirus infection in normal subjects induces a limited, but significant increase in maximal airway narrowing, which is associated with changes in bronchial T-cell numbers. Together with the upregulation of bronchial epithelial intercellular adhesion molecule-1, these findings indicate that, even in healthy subjects, rhinovirus infection affects the intrapulmonary airways.


title: Experimental inoculation of cats with human coronavirus 229E and subsequent challenge with feline infectious peritonitis virus.

text: Minimal-disease cats exposed to live human coronavirus 229E developed homologous antibody responses that suggested little or no replication of the virus in inoculated animals. Oronasal and subcutaneous inoculation of coronavirus 229E did not elicit an antibody response by heterologous (transmissible gastroenteritis virus, canine coronavirus) neutralization or by heterologous (transmissible gastroenteritis virus) kinetics-based enzyme-linked immunosorbent assay. No clinical signs attributable to coronavirus 229E were seen in inoculated cats. Although the number of animals in each of the five experimental groups was small (n = 2), antibodies produced in response to the virus did not appear to sensitize cats to subsequent feline infectious peritonitis virus challenge, but neither did they cross-protect cats against the challenge dose.


title: First report of rabies infection in bats, Molossus molossus, Molossops neglectus and Myotis riparius in the city of São Paulo, State of São Paulo, southeastern Brazil.

text: INTRODUCTION This paper presents the first report of rabies in three bat species, Molossus molossus, Molossops neglectus and Myotis riparius in the city of São Paulo, Brazil. METHODS Bats were diagnosed as positive for rabies using the fluorescent antibody test and mouse inoculation test. The isolates were characterized antigenically using a panel of eight monoclonal antibodies. The samples were also genetically analyzed by partial sequencing of the portion of nucleoprotein gene between positions 1157 and 1445 nt. RESULTS Analysis of the results verified that the sample isolated from the species M. molossus presented antigenic variant 6, while the other two samples showed a different profile from that established in the panel, one not previously reported in the literature. The results of genetic analysis revealed that the M. molossus sample segregated with Lasiurus sp. isolates, M. neglectus segregated with a subgroup of Eptesicus furinalis isolates and the Myotis riparius sample segregated with Myotis sp. isolates. CONCLUSIONS The cases reported in this paper emphasize the need for clarification of the circumstances in which cases of rabies in wildlife occur, principally in urban areas.


title: Respiratory viral and Mycoplasma infections in patients hospitalized for acute asthma.

text: We evaluated the involvement of viral and Mycoplasma infections in severe attacks of asthma in 112 adult patients admitted to Oulu University Central Hospital for an exacerbation of asthma, during a period of one year. The total number of admissions was 151, and specimens for viral identification were collected from 142 of these. Although the methods for diagnosis of rhinoviruses and coronaviruses were lacking, the diagnosis of a viral or Mycoplasma infection was confirmed in 41 patients (29%) by one or more of the three methods; viral serology, viral culture from a throat wash or viral antigen detection from a nasopharyngeal aspirate. Thirty six of these patients (88%) with confirmed infection also had symptoms suggestive of a viral infection. We conclude that viral and Mycoplasma infections are so often involved in severe asthma attacks of adults that they may play an important role in the induction of such attacks.


docid: pndiuoav

title: Global problems and global science.


Preventing HIV transmission among injecting drug users (IDUs) and from IDUs to noninjecting sexual partners in Sichuan, China.


title: Carbon monoxide--related deaths--United States, 1999-2004.

text: Carbon monoxide (CO) is a colorless, odorless, tasteless toxic gas produced by incomplete combustion in fuel-burning devices such as motor vehicles, gas-powered furnaces, and portable generators. Persons with CO poisoning often overlook the symptoms (e.g., headache, nausea, dizziness, or confusion), and undetected exposure can be fatal. Unintentional CO exposure accounts for an estimated 15,000 emergency department visits and 500 unintentional deaths in the United States each year. The most recent state-level estimates of CO-related deaths were described in 1991 for the years 1979-1988. Using the most recent mortality data available, this report updates national and state-specific unintentional, non-fire-related CO mortality rates and describes the demographic, seasonal, and geographic patterns for 1999-2004. During this period, an average of 439 persons died annually from unintentional, non-fire-related CO poisoning, and the national average annual death rate was 1.5 per million persons. However, rates varied by demographic subgroup, month of the year, and state. Rates were highest among adults aged > or =65 years, men, non-Hispanic whites, and non-Hispanic blacks. The average number of deaths was highest during January. Among the states, Nebraska had the highest reliable CO mortality rate. These findings indicate that improved population-based prevention measures, including educating the public about the dangers of CO exposure, are needed at the state and national levels.


title: Detection of bovine torovirus and other enteric pathogens in feces from diarrhea cases in cattle.

text: The objectives of this study were to determine the prevalence of bovine torovirus (BoTV) in bovine fecal samples from diarrhea cases submitted to the Ohio Animal Disease Diagnostic Laboratory (ADDL) and to assess if a relationship exists between BoTV and the other enteric pathogens detected. From November 1999 to May 2001, 259 specimens from 53 calves (< or = 6 months old), 27 young adults (52 years), 125 adults (> or = 2 years), and 54 animals of unknown age were examined by an antigen-capture enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase-polymerase chain reaction (RT-PCR) assay developed to detect BoTV. Testing for other enteric pathogens was performed by ADDL, and the results were analyzed with the BoTV data. The BoTV was detected using ELISA or RT-PCR in 9.7% (25/259) of the clinical samples, 56% (14/25) of which were from calves (P < 0.001) representing 26.4% (14/53) of the calves tested. Of the BoTV-positive calves, 71% (10/14) were less than 3 weeks of age. In 11/25 positive specimens, BoTV was the only pathogen detected among those examined. Other enteric organisms detected alone or in combination with BoTV in calf samples were rotavirus, coronavirus, Salmonella spp., Cryptosporidium spp., and Giardia spp.; but no consistent association between BoTV and these organisms was observed. In summary, BoTV was detected in fecal samples from cattle with diarrhea, principally in young calves less than 3 weeks of age. Future studies of infectious diarrhea in cattle should also include assays for this etiologic agent.


Childhood SARS in Singapore.


Influenza pandemic preparedness: legal and ethical dimensions.


title: The relationship between serum interleukins and T-lymphocyte subsets in patients with severe acute respiratory syndrome.

text: OBJECTIVES To observe the changes of serum interleukins (IL), T-lymphocyte subsets, and white blood cell (WBC) count in patients with severe acute respiratory syndrome (SARS), and to investigate the relationship between injured immune function, immune response and disturbed immune adjustment in SARS patients. METHODS The levels of serum IL-2, IL-10, IL-12 and T-lymphocyte subset counts were measured in 35 clinically diagnosed SARS patients by using enzyme linked immunosorbant assay (ELISA). The relationship between the measured results and WBC count was further analyzed. RESULTS The level of serum IL was increased to a great extent in the 35 SARS patients, and the levels of serum IL-2, IL-10 and IL-12 were 242.53 (92.69) pg/ml, 77.43 (63.37) pg/ml and 65.94 (43.21) pg/ml, respectively. The level of serum IL-2 increased markedly (P < 0.01). The peripheral blood CD(3)(+), CD(4)(+) and CD(8)(+) counts were lower than normal in 23 patients (67.7%), 26 patients (74.3%) and 15 patients (42.9%), respectively. The peripheral blood WBC counts were lower than 4.0 x 10(9)/L in 10 patients, and their CD(3)(+), CD(4)(+) and CD(8)(+) counts were 583.90 (315.58) x 10(6)/L, 272.00 (94.13) x 10(6)/L and 209.00 (72.21) x 10(6)/L, respectively. The peripheral blood WBC counts were (4.0 - 10.0) x 10(9)/L in 20 patients, and their CD(3)(+), CD(4)(+) and CD(8)(+) counts were 700.00 (502.96) x 10(6)/L, 347.00 (247.58) x 10(6)/L and 322.05 (228.47) x 10(6)/L, respectively. The peripheral blood WBC counts were higher than 10.0 x 10(9)/L in 5 patients, and their CD(3)(+), CD(4)(+) and CD(8)(+) counts were 1466.00 (630.86) x 10(6)/L, 783.00 (311.14) x 10(6)/L and 640.00 (294.40) x 10(6)/L, respectively. The decreased CD(3)(+), CD(4)(+) and CD(8)(+) counts were consistent with the decreased WBC counts. The level of IL in SARS patients was significantly higher than that in patients with chronic hepatitis B (P < 0.01). CONCLUSIONS The level of serum IL is closely related to cell immunity in SARS patients. The level of serum IL is increased evidently while CD(3)(+), CD(4)(+) and CD(8)(+) counts decrease. Both serum IL and CD are associated with injury of immune function, and thus they could be regarded as a monitoring index for judging the condition of SARS patients and prescribing immune therapy.


SARS challenges therapeutics.


title: Arterivirus subgenomic mRNA synthesis and virion biogenesis depend on the multifunctional nsp1 autoprotease.

text: Many groups of plus-stranded RNA viruses produce additional, subgenomic mRNAs to regulate the expression of part of their genome. Arteriviruses and coronaviruses (order Nidovirales) are unique among plus-stranded RNA viruses for using a mechanism of discontinuous RNA synthesis to produce a nested set of 5'- and 3'-coterminal subgenomic mRNAs, which serve to express the viral structural protein genes. The discontinuous step presumably occurs during minus-strand synthesis and joins noncontiguous sequences copied from the 3'- and 5'-proximal domains of the genomic template. Nidovirus genome amplification ("replication") and subgenomic mRNA synthesis ("transcription") are driven by 13 to 16 nonstructural proteins (nsp's), generated by autocatalytic processing of two large "replicase" polyproteins. Previously, using a replicon system, the N-terminal nsp1 replicase subunit of the arterivirus equine arteritis virus (EAV) was found to be dispensable for replication but crucial for transcription. Using reverse genetics, we have now addressed the role of nsp1 against the background of the complete EAV life cycle. Mutagenesis revealed that nsp1 is in fact a multifunctional regulatory protein. Its papain-like autoprotease domain releases nsp1 from the replicase polyproteins, a cleavage essential for viral RNA synthesis. Several mutations in the putative N-terminal zinc finger domain of nsp1 selectively abolished transcription, while replication was either not affected or even increased. Other nsp1 mutations did not significantly affect either replication or transcription but still dramatically reduced the production of infectious progeny. Thus, nsp1 is involved in at least three consecutive key processes in the EAV life cycle: replicase polyprotein processing, transcription, and virion biogenesis.


title: Processing of open reading frame 1a replicase proteins nsp7 to nsp10 in murine hepatitis virus strain A59 replication.

text: Coronaviruses express open reading frame 1a (ORF1a) and ORF1b polyproteins from which 16 nonstructural proteins (nsp) are derived. The highly conserved region at the carboxy terminus of ORF1a is processed by the nsp5 proteinase (Mpro) into mature products, including nsp7, nsp8, nsp9, and nsp10, proteins with predicted or identified activities involved in RNA synthesis. Although continuous translation and proteolytic processing of ORF1ab by Mpro is required for replication, it is unknown whether specific cleavage events within the polyprotein are dispensable. We determined the requirement for the nsp7 to nsp10 proteins and their processing during murine hepatitis virus (MHV) replication. Through use of an MHV reverse genetics system, in-frame deletions of the coding sequences for nsp7 to nsp10, or ablation of their flanking Mpro cleavage sites, were made and the effects upon replication were determined. Viable viruses were characterized by analysis of Mpro processing, RNA transcription, and growth fitness. Deletion of any of the regions encoding nsp7 to nsp10 was lethal. Disruption of the cleavage sites was lethal with the exception of that of the nsp9-nsp10 site, which resulted in a mutant virus with attenuated replication. Passage of the attenuated nsp9-nsp10 cleavage mutant increased fitness to near-wild-type kinetics without reversion to a virus capable of processing nsp9-nsp10. We also confirmed the presence of a second cleavage site between nsp7 and nsp8. In order to determine whether a distinct function could be attributed to preprocessed forms of the polyprotein, including nsp7 to nsp10, the genes encoding nsp7 and nsp8 were rearranged. The mutant virus was not viable, suggesting that the uncleaved protein may be essential for replication or proteolytic processing.


title: Drug targets in severe acute respiratory syndrome (SARS) virus and other coronavirus infections.

text: Coronaviruses are important human and animal pathogens of the order Nidovirales. Several new members were discovered following the emergence of SARS-CoV in human populations, including two human coronaviruses and several animal coronaviruses. They cause respiratory and gastrointestinal illnesses and have been found in the brains of patients with multiple sclerosis. The high mortality of SARS, the identification of a natural reservoir, and the well-founded fear of provoking antibody-enhanced disease as a result of vaccination fueled the ongoing efforts in anti-coronavirus drug discovery. This review presents the results of current research.


title: Coronavirus infection in a litter of pups.

text: An outbreak of a coronavirus infection in a litter of 10-week-old poodle pups from a commercial kennel is described. Coronavirus-like particles were demonstrated by electron microscopy in the intestinal contents and in the colonic mucosa. Treponemas and campylobacters were excreted in great numbers in the faeces. The gastrointestinal disturbances were complicated by hepatic and renal degeneration and severe bronchopneumonia.


title: Inbreeding depression increases susceptibility to bovine tuberculosis in lions: an experimental test using an inbred-outbred contrast through translocation.

text: Disease can dramatically influence the dynamics of endangered wildlife populations, especially when they are small and isolated, with increased risk of inbreeding. In Hluhluwe-iMfolozi Park (HiP), a small, enclosed reserve in South Africa, a large lion (Panthera leo) population arose from a small founder group in the 1960s and started showing conspicuous signs of inbreeding. To restore the health status of the HiP lion population, outbred lions were translocated into the existing population. In this study, we determined the susceptibility to bovine tuberculosis (bTB), and the prevalence of antibody to feline viruses of native lions, and compared the findings with those from translocated outbred lions and their offspring. Antibodies to feline herpesvirus, feline calicivirus, feline parvovirus, and feline coronavirus were present in the lion population, but there was no significant difference in antibody prevalence between native and translocated lions and their offspring, and these feline viruses did not appear to have an effect on the clinical health of HiP lions. However, feline immunodeficiency virus (FIV), which was previously absent from HiP, appears to have been introduced into the lion population through translocation. Within 7 yr, the prevalence of antibody to FIV increased up to 42%. Bovine tuberculosis posed a major threat to the inbred native lion population, but not to translocated lions and their offspring. More than 30% of the native lion population died from bTB or malnutrition compared with <2% of the translocated lions and their offspring. We have demonstrated that management of population genetics through supplementation can successfully combat a disease that threatens population persistence. However, great care must be taken not to introduce new diseases into populations through translocation.


title: Serologic evidence of coronavirus infection in New York and New England dairy cattle with winter dysentery.

text: Acute and convalescent sera were collected from 8 dairy herds with classic clinical features of winter dysentery. An enzyme-linked immunosorbent assay was used to measure coronavirus antibody titers, employing calf diarrhea coronavirus as antigen. Twenty-two of the 35 animals tested (63%) showed a greater than or equal to 4-fold seroconversion. Adult cattle in all 8 herds seroconverted. These findings complement previously reported immunoperoxidase and electron microscopic evidence, suggesting an etiologic role for an enteric coronavirus in this disease.


title: Cutting edge: anti-tumor necrosis factor therapy in rheumatoid arthritis inhibits memory B lymphocytes via effects on lymphoid germinal centers and follicular dendritic cell networks.

text: Rheumatoid arthritis (RA) is mediated by a proinflammatory cytokine network with TNF at its apex. Accordingly, drugs that block TNF have demonstrated significant efficacy in the treatment of RA. A great deal of experimental evidence also strongly implicates B cells in the pathogenesis of RA. Yet, it remains unclear whether these two important players and the therapies that target them are mechanistically linked. In this study we demonstrate that RA patients on anti-TNF (etanercept) display a paucity of follicular dendritic cell networks and germinal center (GC) structures accompanied by a reduction in CD38+ GC B cells and peripheral blood memory B cell lymphopenia compared with healthy controls and RA patients on methotrexate. This study provides initial evidence in humans to support the notion that anti-TNF treatment disrupts GC reactions at least in part via effects on follicular dendritic cells.


title: Molecular diagnostic methods in pneumonia.

text: PURPOSE OF REVIEW Molecular techniques offer the promise of improving diagnosis of lower respiratory tract infections. This review focuses on currently used molecular diagnostic techniques for various types of pneumonia and highlights potential future applications of this technology. RECENT FINDINGS Lower respiratory tract infections result in a high degree of morbidity and mortality, but a definitive microbiologic diagnosis is often not obtained by traditional culture or serologic methods. In addition, culture of certain organisms may be difficult or require extended periods of time. Molecular techniques have the potential to improve diagnostic yield and decrease time to pathogen identification. These techniques are also helpful in the determination of drug sensitivity and the understanding of transmission and outbreaks. Most currently used techniques employ some variation of the polymerase chain reaction. Limitations include high costs, the need for specialized equipment, and problems with false-positive and -negative results. SUMMARY Molecular diagnosis of pneumonia has the potential to improve identification of pathogens in patients with suspected lower respiratory tract infection. Limitations of molecular techniques currently prevent their widespread use, but future developments will likely lead to inclusion of these tests in routine diagnostic evaluations.


SARS may have a silver lining, WHO says.


title: Development and implementation of a nationwide health care quality indicator system in Taiwan.

text: UNLABELLED QUALITY ISSUES: Quality is an increasingly important issue to the health care sector. The Taiwanese government also recognizes the need to implement a nationwide health care quality indicator system to strengthen quality surveillance. CHOICE OF SOLUTION In 1999, the Department of Health funded a 2-year project led by the Taiwan Healthcare Executive College to develop a comprehensive performance assessment system, subsequently named as Taiwan Healthcare Indicator Series (THIS). The series includes four categories of indicators, namely outpatient, in-patient, emergency care, and intensive care, and has 139 items in total. IMPLEMENTATION The system was officially launched in 2001. Participation is voluntary. The Taiwan Healthcare Executive College processes the data and provides feedback to the participating hospitals. The information is for the participating hospitals' own use and is not released to the public. EVALUATION Participating hospitals have increased from 45 in 2001 to 227 in 2006 and now constitute approximately 50% of the total hospital population in Taiwan. The reporting rate averaged 77.7% in 2004. The first five most reported indicators are the percentage of first-visit outpatients to outpatient clinics, the average length of in-patient stay, the nosocomial infection rate, the occupancy rate, and the crude mortality rate. LESSONS LEARNED How the data are interpreted and how data interpretation can lead to quality improvement are the principal concerns of participating hospitals. In light of the success of the indicator series, the Bureau of National Health Insurance (BNHI) of Taiwan has proposed participation in the series as being one of the criteria to be reimbursed for quality.


title: Suppressing epidemics with a limited amount of immunization units.

text: The way diseases spread through schools, epidemics through countries, and viruses through the internet is crucial in determining their risk. Although each of these threats has its own characteristics, its underlying network determines the spreading. To restrain the spreading, a widely used approach is the fragmentation of these networks through immunization, so that epidemics cannot spread. Here we develop an immunization approach based on optimizing the susceptible size, which outperforms the best known strategy based on immunizing the highest-betweenness links or nodes. We find that the network's vulnerability can be significantly reduced, demonstrating this on three different real networks: the global flight network, a school friendship network, and the internet. In all cases, we find that not only is the average infection probability significantly suppressed, but also for the most relevant case of a small and limited number of immunization units the infection probability can be reduced by up to 55%.


title: Modeling Epidemics Spreading on Social Contact Networks.

text: Social contact networks and the way people interact with each other are the key factors that impact on epidemics spreading. However, it is challenging to model the behavior of epidemics based on social contact networks due to their high dynamics. Traditional models such as susceptible-infected-recovered (SIR) model ignore the crowding or protection effect and thus has some unrealistic assumption. In this paper, we consider the crowding or protection effect and develop a novel model called improved SIR model. Then, we use both deterministic and stochastic models to characterize the dynamics of epidemics on social contact networks. The results from both simulations and real data set conclude that the epidemics are more likely to outbreak on social contact networks with higher average degree. We also present some potential immunization strategies, such as random set immunization, dominating set immunization, and high degree set immunization to further prove the conclusion.