title: Ellagic Acid-Changed Epigenome of Ribosomal Genes and Condensed RPA194-Positive Regions of Nucleoli in Tumour Cells.

text: We studied the effect of ellagic acid (EA) on the morphology of nucleoli and on the pattern of major proteins of the nucleolus. After EA treatment of HeLa cells, we observed condensation of nucleoli as documented by the pattern of argyrophilic nucleolar organizer regions (AgNORs). EA also induced condensation of RPA194-positive nucleolar regions, but no morphological changes were observed in nucleolar compartments positive for UBF1/2 proteins or fibrillarin. Studied morphological changes induced by EA were compared with the morphology of control, non-treated cells and with pronounced condensation of all nucleolar domains caused by actinomycin D (ACT-D) treatment. Similarly as ACT-D, but in a lesser extent, EA induced an increased number of 53BP1-positive DNA lesions. However, the main marker of DNA lesions, γH2AX, was not accumulated in body-like nuclear structures. An increased level of γH2AX was found by immunofluorescence and Western blots only after EA treatment. Intriguingly, the levels of fibrillarin, UBF1/2 and γH2AX were increased at the promoters of ribosomal genes, while 53BP1 and CARM1 levels were decreased by EA treatment at these genomic regions. In the entire genome, EA reduced H3R17 dimethylation. Taken together, ellagic acid is capable of significantly changing the nucleolar morphology and protein levels inside the nucleolus.


title: Efficacy and safety of topical combinations of ipratropium and xylometazoline for the treatment of symptoms of runny nose and nasal congestion associated with acute upper respiratory tract infection.

text: BACKGROUND Rhinorrhea and nasal congestion are simultaneous symptoms associated with the common cold. This study investigated the efficacy and safety of a combination nasal spray of ipratropium and xylometazoline for simultaneous treatment of these symptoms. METHODS The trial was a multicenter double-blind, parallel-group, randomized design on patients with common cold symptoms. Patients scored symptoms of runny nose and nasal congestion and recorded adverse events in a diary for up to 7 days. Patients also recorded tissue use. The five test treatments consisted of ipratropium, 0.6 mg/mL, and xylometazoline, 1.0 mg/mL; ipratropium, 0.6 mg/mL, and xylometazoline, 0.5 mg/mL; ipratropium, 0.6 mg/mL; xylometazoline, 1.0 mg/mL; and placebo solution. RESULTS Eight hundred sixty-four patients were screened and 786 patients received treatment. One day after treatment there was a clear separation between the scores for the placebo and ipratropium treatment groups for rhinorrhea and between the placebo and xylometazoline treatment groups for congestion. Both ipratropium/xylometazoline 1.0 and ipratropium/xylometazoline 0.5 treatments were superior to xylometazoline with respect to rhinorrhea (p < 0.0001) and superior to ipratropium with respect to nasal congestion scores (p < 0.001). Both the ipratropium combination treatments had significantly lower tissue use than the xylometazoline treatment group (p < 0.0001). Adverse events were distributed equally between the treatments, except mucus tinged with blood, epistaxis, nasal passage irritation, and nasal dryness, which had a higher incidence in the three groups that received medicines containing ipratropium. CONCLUSION The results indicate that a combination medicine of ipratropium and xylometazoline is safe and effective for treatment of rhinorrhea and nasal congestion associated with common cold.


title: Randomized controlled trial of sequential intravenous (i.v.) and oral moxifloxacin compared with sequential i.v. and oral co-amoxiclav with or without clarithromycin in patients with community-acquired pneumonia requiring initial parenteral treatment.

text: The objective of the present trial was to compare the efficacy, safety, and tolerability of moxifloxacin (400 mg) given intravenously (i.v.) once daily followed by oral moxifloxacin (400 mg) for 7 to 14 days with the efficacy, safety, and tolerability of co-amoxiclav (1.2 g) administered by i.v. infusion three times a day followed by oral co-amoxiclav (625 mg) three times a day, with or without clarithromycin (500 mg) twice daily (i.v. or orally), for 7 to 14 days in adult patients with community-acquired pneumonia requiring initial parenteral therapy. A total of 628 patients were enrolled and assessed by evaluation of their clinical and bacteriological responses 5 to 7 days and 21 to 28 days after administration of the last dose of study medication. Although the trial was designed, on the basis of predefined outcomes, to demonstrate the equivalence of the two regimens, the results showed statistically significant higher clinical success rates (for moxifloxacin, 93.4%, and for comparator regimen, 85.4%; difference [Delta], 8.05%; 95% confidence interval [CI], 2.91 to 13.19%; P = 0.004) and bacteriological success rates (for moxifloxacin, 93.7%, and for comparator regimen, 81.7%; Delta, 12.06%; 95% CI, 1.21 to 22.91%) for patients treated with moxifloxacin. This superiority was seen irrespective of the severity of the pneumonia and whether or not the combination therapy included a macrolide. The time to resolution of fever was also statistically significantly faster for patients who received moxifloxacin (median time, 2 versus 3 days), and the duration of hospital admission was approximately 1 day less for patients who received moxifloxacin. The treatment was converted to oral therapy immediately after the initial mandatory 3-day period of i.v. administration for a larger proportion of patients in the moxifloxacin group than patients in the comparator group (151 [50.2%] versus 57 [17.8%] patients). There were fewer deaths (9 [3.0%] versus 17 [5.3%]) and fewer serious adverse events (38 [12.6%] versus 53 [16.5%]) in the moxifloxacin group than in the comparator group. The rates of drug-related adverse events were comparable in both groups (38.9% in each treatment group). The overall incidence of laboratory abnormalities was similar in both groups. Thus, it is concluded that monotherapy with moxifloxacin is superior to that with a standard combination regimen of a beta-lactam and a beta-lactamase inhibitor, co-amoxiclav, with or without a macrolide, clarithromycin, in the treatment of patients with community-acquired pneumonia admitted to a hospital.


title: A novel high aspect ratio microfluidic design to provide a stable and uniform microenvironment for cell growth in a high throughput mammalian cell culture array.

text: We present a high aspect ratio microfluidic device for culturing cells inside an array of microchambers with continuous perfusion of medium. The device was designed to provide a potential tool for cost-effective and automated cell culture. The single unit of the array consists of a circular microfluidic chamber 40 microm in height surrounded by multiple narrow perfusion channels 2 microm in height. The high aspect ratio (approximately 20) between the microchamber and the perfusion channels offers advantages such as localization of the cells inside the microchamber as well as creating a uniform microenvironment for cell growth. Finite element methods were used to simulate flow profile and mass transfer of the device. Human carcinoma (HeLa) cells were cultured inside the device with continuous perfusion of medium at 37 degrees C and was grown to confluency. The microfluidic cell culture array could potentially offer an affordable platform for a wide range of applications in high throughput cell-based screening, bioinformatics, synthetic biology, quantitative cell biology, and systems biology.


title: [Roentgenography and CT appearance in patients with severe acute respiratory syndrome].

text: OBJECTIVE To evaluate the appearance and dynamic change of chest roentgenography and CT in patients with severe acute respiratory syndrome (SARS). METHODS Serial roentgenography and CT of 61 confirmed SARS patients were analyzed. RESULTS The onset symptom was fever in all patients. In the early phase of SARS, the main abnormal appearance was single or bilateral localized patchy clouding opacity on roentgenography, which progressed rapidly. The area of opacity peaked at about 2 weeks, involving the majority area of the lung in 57% of the patients. The area involved was correlated with the severity of clinical symptoms. The opacity disappeared gradually in 5 weeks in 84% of the patients. Lungs complicated infection were found in 6 patients with a prolonged duration of the illness. Among the 61 patients, 4 died. CT scan was performed in 16 SARS patients in the recovery phase, of whom 13 showed lung fibrosis. CONCLUSIONS Lung infiltration in early phase develops rapidly and involves most area of the lung in advanced phase in most SARS patients. Lungs fibrosis was found in some patients in the recovery phase.


title: Orchitis in roosters with reduced fertility associated with avian infectious bronchitis virus and avian metapneumovirus infections.

text: The pathogenesis of infection involving both infectious bronchitis virus (IBV) and avian metapneumovirus (aMPV) causes reproductive damage in hens after viral replication in the epithelium of the oviduct, resulting in loss of cilia and degeneration and necrosis of the epithelial and glandular cells. Although IBV has been indicated as a possible cause of the formation of calcium stones in the epididymus of roosters, a definitive association has not been confirmed. This report describes the detection of IBV and aMPV in the testes of roosters from a Brazilian poultry broiler breeder's flock with epididymal stones and low fertility. Samples of testis, trachea, and lungs from breeder males aged 57 wk were positive for IBV by reverse transcriptase-polymerase chain reaction (RT-PCR), and virus isolation and testis samples were also positive for aMPV by RT-PCR. The inoculation of testis samples into embryonated chicken eggs via the allantoic cavity resulted in curled, hemorrhagic, and stunted embryos typical of IBV infection. The allantoic fluid was positive by RT-PCR aimed to amplify the region coding for the S1 subunit of the IBV S gene, but it was not positive for aMPV. Sequence analysis of the amplified fragment revealed a close relationship with European IBV genotype D274, previously unreported in Brazil. These results indicate that IBV and perhaps aMPV are likely to have played a role in the pathogenesis of the testicular disease described and should be regarded as factors that can influence male fertility disease in chickens.


title: Viable porcine arteriviruses with deletions proximal to the 3' end of the genome.

text: In order to obtain attenuated live vaccine candidates of porcine reproductive and respiratory syndrome virus (PRRSV), a series of deletions was introduced at the 3' end of the viral genome using an infectious cDNA clone of the Lelystad virus isolate. RNA transcripts from the full-length cDNA clones were transfected into BHK-21 cells. The culture supernatant of these cells was subsequently used to infect porcine alveolar macrophages to detect the production of progeny virus. It is shown that C-terminal truncation of the nucleocapsid (N) protein, encoded by ORF7, was tolerated for up to six amino acids without blocking the production of infectious virus. Mutants containing larger deletions produced neither virus nor virus-like particles containing viral RNA. Deletion analysis of the 3' UTR immediately downstream of ORF7 showed that infectious virus was still produced after removal of seven nucleotides behind the stop codon of ORF7. Deletion of 32 nucleotides in this region abolished RNA replication and, consequently, no infectious virus was formed. Serial passage on porcine alveolar macrophages demonstrated that the viable deletion mutants were genetically stable at the site of mutation. In addition, the deletions did not affect the growth properties of the recombinant viruses in vitro, while their antigenic profiles were similar to that of wild-type virus. Immunoprecipitation experiments with the six-residue N protein-deletion mutant confirmed that the truncated protein was indeed smaller than the wild-type N protein. The deletion mutants produced in this study are interesting candidate vaccines to prevent PRRS disease in pigs.


title: Genomic RNA sequence of Feline coronavirus strain FIPV WSU-79/1146.

text: A consensus sequence of the Feline coronavirus (FCoV) (strain FIPV WSU-79/1146) genome was determined from overlapping cDNA fragments produced by RT-PCR amplification of viral RNA. The genome was found to be 29 125 nt in length, excluding the poly(A) tail. Analysis of the sequence identified conserved open reading frames and revealed an overall genome organization similar to that of other coronaviruses. The genomic RNA was analysed for putative cis-acting elements and the pattern of subgenomic mRNA synthesis was analysed by Northern blotting. Comparative sequence analysis of the predicted FCoV proteins identified 16 replicase proteins (nsp1-nsp16) and four structural proteins (spike, membrane, envelope and nucleocapsid). Two mRNAs encoding putative accessory proteins were also detected. Phylogenetic analyses confirmed that FIPV WSU-79/1146 belongs to the coronavirus subgroup G1-1. These results confirm and extend previous findings from partial sequence analysis of FCoV genomes.


title: Comparative host gene transcription by microarray analysis early after infection of the Huh7 cell line by SARS coronavirus and human coronavirus 229E.

text: During the early stages of infection, SARS-CoV produces more severe perturbation of host cell gene expression in a human epithelial cell line of liver origin than the HCoV-229E.


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title: United States.

text: United States Determined lobbying by American nurses has helped secure more funds for AIDS treatment and prevention in the United States.


title: Non-Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology.

text: This selection from the NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) focuses on targeted therapies and immunotherapies for metastatic NSCLC, because therapeutic recommendations are rapidly changing for metastatic disease. For example, new recommendations were added for atezolizumab, ceritinib, osimertinib, and pembrolizumab for the 2017 updates.


title: Ethics in research.

text: PURPOSE OF REVIEW This review will examine research ethics in the context of globalization of clinical trials and recent rapid developments in bioscience. It will focus on international ethical guidelines and the functions of research ethics review boards in research governance. Consent issues in genetic research, which must comply with privacy laws by protecting confidentiality and privacy of personal health data, will be discussed. RECENT FINDINGS There has been a rapid expansion of genomic and proteonomic research and biotechnology in the last decade. International ethical guidelines have been updated and the bioscience industry has developed ethics policies. At the same time, problems in academic anesthesia in the US and UK have been identified, leading to recommendations to train physician-scientists in anesthesia to stimulate research activity in the future. Anesthesiologists are joining interdisciplinary research teams and the concept of evidence-based translational research is emerging. SUMMARY Anesthesiologists are moving towards participation in interdisciplinary research teams. They are well placed to speed the translation of research discovery into clinical practice and provide evidence-based perioperative care. This review provides the ethical framework that anesthesiologists will need to meet the challenges of this changing pattern of practice.


title: Newcastle disease virus, a host range-restricted virus, as a vaccine vector for intranasal immunization against emerging pathogens.

text: The international outbreak of the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) in 2002-2003 highlighted the need to develop pretested human vaccine vectors that can be used in a rapid response against newly emerging pathogens. We evaluated Newcastle disease virus (NDV), an avian paramyxovirus that is highly attenuated in primates, as a topical respiratory vaccine vector with SARS-CoV as a test pathogen. Complete recombinant NDV was engineered to express the SARS-CoV spike S glycoprotein, the viral neutralization and major protective antigen, from an added transcriptional unit. African green monkeys immunized through the respiratory tract with two doses of the vaccine developed a titer of SARS-CoV-neutralizing antibodies comparable with the robust secondary response observed in animals that have been immunized with a different experimental SARS-CoV vaccine and challenged with SARS-CoV. When animals immunized with NDV expressing S were challenged with a high dose of SARS-CoV, direct viral assay of lung tissues taken by necropsy at the peak of viral replication demonstrated a 236- or 1,102-fold (depending on the NDV vector construct) mean reduction in pulmonary SARS-CoV titer compared with control animals. NDV has the potential for further development as a pretested, highly attenuated, intranasal vector to be available for expedited vaccine development for humans, who generally lack preexisting immunity against NDV.


title: Type 1 wild poliovirus and putative enterovirus 109 in an outbreak of acute flaccid paralysis in Congo, October-November 2010.

text: An outbreak of flaccid paralysis syndrome in adults is ongoing in Congo. Molecular analysis of faecal, throat and cerebrospinal samples identified wildtype 1 poliovirus and an additional enterovirus C strain related to enterovirus 109 as the cause. As of 22 November, the cumulative number of cases was 409, of which 169 (41.3%) were fatal. This is one of the largest wild type 1 poliovirus outbreaks ever described associated with an unusually high case fatality rate.


title: Antiviral therapy of influenza.

text: Influenza viruses are a leading cause of morbidity and mortality worldwide despite the availability of an effective vaccine. The emergence of highly pathogenic avian influenza viruses in southeast Asia, which can infect and kill humans and for which there is no vaccine, has heightened the need to establish a supply of effective antivirals. Two effective classes of anti-influenza drugs are currently available, and many attractive targets exist for further development. This review presents the current status of antiviral therapy of, and highlights the challenges presented by, the threat of pandemic influenza.


title: Prognosis of COVID-19: Changes in laboratory parameters.

text: INTRODUCTION Since December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome - Coronavirus 2 (SARS-CoV-2) emerged in China and has become a global threat. Comparison of hematological parameters between mild and severe cases of SARS-CoV 2 is so far limited, but significant differences in parameters such as interleukin-6, d-dimers, glucose, fibrinogen and C-reactive protein have been already reported. PURPOSE In this study we analyzed the changes observed in easily measured blood biomarkers in the patients and provided evidence of how these markers can be used as prognostic factors of the disease. METHODS Demographic characteristics, detailed medical history, and laboratory findings of all enrolled SARS-CoV 2 infection positive patients who were referred to Patras University Hospital from the period of March 4th 2020 (when first confirmed case in Greece appeared in our hospital) until April 4th 2020 were extracted from electronic medical records and analyzed. RESULTS We provided evidence that some very common laboratory values can be used as independent predictive factors in SARS-CoV 2 infection. Despite the retrospective nature of this study and the small number of subjects analyzed, we showed that NLR, LDH, d-dimers, CRP, fibrinogen and ferritin can be used early at the patient's first visit for SARS-CoV 2 infection symptoms and can predict the severity of infection. CONCLUSION More studies are warranted to further objectively confirm the clinical value of prognostic factors related to SARS-CoV 2 and establish an easy-to-get panel of laboratory findings for evaluating the disease severity.


title: Leader sequences of murine coronavirus mRNAs can be freely reassorted: evidence for the role of free leader RNA in transcription.

text: Mouse hepatitis virus (MHV), which replicates in cytoplasm of infected cells, contains an identical leader RNA sequence at the 5' end of each of the virus-specific mRNAs. Previous studies suggested that the synthesis of these mRNAs does not involve conventional RNA splicing and may instead require priming by a free leader RNA. In this communication, we demonstrate that, during a mixed infection with two different MHVs, the leader RNA sequences from one virus could be detected on the mRNAs of the coinfecting virus at a high frequency, as if the leader sequence and mRNAs were joined together from two randomly segregating RNA segments. This finding demonstrates that MHV mRNA transcription utilizes independently transcribed leader RNA species that possess the trans-acting property. This study thus provides further evidence in support of the unique model of "leader-primed transcription" for coronavirus mRNA synthesis.


title: Neurovirulence of murine coronavirus JHM temperature-sensitive mutants in rats.

text: The murine coronavirus strain JHM is highly neurotropic in rats and has a marked tendency to cause demyelinating central nervous system diseases after intracerebral inoculation. The clinical diseases observed range from an acute encephalomyelitis occurring within 2 weeks postinfection to a subacute demyelinating encephalomyelitis developing several weeks or months postinfection. Uncloned wild-type virus induced both acute and subacute diseases, whereas cloned JHM virus grown in tissue culture caused only acute disease without the pronounced lesions of primary demyelination. In contrast, temperature-sensitive mutants selected from that clone were capable of inducing subacute demyelinating encephalomyelitis after prolonged incubation times. Viruses recovered from diseased animals were still temperature sensitive. Inoculation of temperature-sensitive mutants into suckling rats (age, 10 to 15 days) produced high rates of subacute demyelinating diseases running a more chronic course; these diseases often were not fatal. Those rats which did not show clinical signs frequently revealed inflammatory demyelinating lesions. These findings indicate that the rate and type of clinical disease are dependent on the neurovirulence of the virus mutant used for inoculation and the age of the animals at the time of infection.


title: Virus-receptor interactions in the enteric tract. Virus-receptor interactions.

text: Expression of specific virus receptors on the surface of intestinal epithelial cells or M cells can determine whether or not a animal is susceptible to infection with an enterotropic virus. Receptors for many animal viruses have been identified. The specificity of virus-receptor interactions clearly affects the species specificity of virus infection, and in some instances may be an important determinant of viral tissue tropism. In this paper, the specificity of coronavirus-receptor interactions is summarized. Porcine and human coronaviruses utilize aminopeptidase N as their receptors, but in a species-specific manner. Mouse hepatitis virus uses several rodent glycoproteins in the carcinoembryonic antigen family as receptors. In addition, some coronaviruses can interact with carbohydrate moieties on the cell surface. Understanding the molecular mechanisms of virus-receptor interactions may lead to development of novel strategies for the control of enteric viral diseases.


title: Prevention and treatment of viral respiratory infections by traditional Chinese herbs.

text: OBJECTIVE This review focuses on current knowledge of traditional Chinese herbs on prevention and treatment of viral respiratory infections, especially caused by Severe Acute Respiratory Syndromes (SARS) virus, respiratory syncytial virus (RSV) and influenza viruses. DATA SOURCES The data used in this review were obtained from PubMed and CNKI up to May 2013. Terms of Chinese herbs and infections of respiratory tract were used in the search. STUDY SELECTION Articles related that Chinese herbs preventing and treating infections in respiratory tract were retrieved and reviewed. The risk of bias of included studies was assessed by the method in the "Cochrane Handbook of Systematic Reveiws of Interventionsand studies" with high risk of bias were excluded. Four criteria for selections were set as following: randomized controlled trial, particular effective compound or derivative, reproducible result and animal test. RESULTS Infectious respiratory tract diseases cause most mortality among infectious illnesses around the world. As traditional medicines, Chinese herbs have been widely used to deal with diseases for centuries and have been proved effective in practice. The administration of some Chinese herbs stimulates, suppresses or regulates the activity of immune system, thus protecting the respiratory tract or relieving infections of pathogens. Many herbs have remarkable antiviral effects, therefore they are used as substitutes of antimicrobial drugs. Based on the theory of traditional Chinese medicine, mix-using herbs provide a synergistic benefit on preventing and healing respiratory tract infections. Many commercial herbal medicines containing one or more compounds have been successfully applied to prevent and treat viral infections of respiratory tract clinically. CONCLUSIONS Traditional Chinese herbs could directly inhibit pathogens infecting respiratory tract, or coordinate the activity of immune system to avoid or relieve infections. With the emergence of antidrug pathogens or new variants, Chinese herbs give strong evidence to protect human health.


title: Severe respiratory illness associated with a novel coronavirus--Saudi Arabia and Qatar, 2012.

text: CDC is working closely with the World Health Organization (WHO) and other partners to better understand the public health risk presented by a recently detected, novel coronavirus. This virus has been identified in two patients, both previously healthy adults who suffered severe respiratory illness. The first patient, a man aged 60 years from Saudi Arabia, was hospitalized in June 2012 and died; the second patient, a man aged 49 years from Qatar with onset of symptoms in September 2012 was transported to the United Kingdom for intensive care. He remains hospitalized on life support with both pulmonary and renal failure. Person-to-person or health-care-associated transmission has not been identified to date. Interim case definitions based on acute respiratory illness and travel history were issued by WHO on September 29 and include criteria for "patient under investigation," "probable case," and "confirmed case". This information is current as of October 4. Updates on the investigation and the WHO case definition are available at http://www.who.int/csr/don/en/index.html.


title: Laparoscopic vasectomy in African savannah elephant (Loxodonta africana); surgical technique and results.

text: Several small, enclosed reserves in southern Africa are experiencing significant elephant population growth, which has resulted in associated environmental damage and changes in biodiversity. Although several techniques exist to control elephant populations, e.g., culling, relocation, and immunocontraception, the technique of laparoscopic vasectomy of free-ranging bull elephants was investigated. Bilateral vasectomies were performed in 45 elephants. Of these elephants, one died within 24 hr of recovery and two had complications during surgery but recovered uneventfully. Histologic examination confirmed the resected tissue as ductus deferens in all the bulls. Most animals recovered uneventfully and showed no abnormal behavior after surgery. Complications recorded included incisional dehiscence, 1 full-thickness and 2 partial-thickness lacerations of the large intestine, and initial sling-associated complications, for example, deep radial nerve paresis. One bull was found dead 6 weeks after surgery without showing any prior abnormal signs. Vasectomy in free-ranging African bull elephants may be effectively performed in their normal environment. The surgical procedure can be used as a realistic population management tool in free-ranging elephants without major anesthetic, surgical, or postoperative complications.


title: Expression of avian infectious bronchitis virus multi-epitope based peptide EpiC in Lactococcus lactis for oral immunization of chickens.

text: The avian infectious bronchitis virus (IBV) multi-epitope based peptide EpiC was found to be effective in inducing strong humoral and cellular responses against IBV. In this study, the gene EpiC was introduced into Lactococcus lactis NZ3900, and three recombinant strains expressing EpiC in intracellular and extracellular forms were constructed. SDS-PAGE and Western blot results indicated that EpiC was successfully expressed and had good immunoreactivity with chicken anti-IBV serum. Fusion of the signal pepitide gene SPusp45 and the nine-peptide LEISSTCDA encoding oligonucleotide to EpiC increased the secretion of EpiC, but reduced the total yields of EpiC. Oral immunization to specific-pathogen-free (SPF) chickens with recombinant strains induced significantly higher levels of humoral immune responses, and provided protection against lethal dose challenge by the IBV SAIBk strain. These results indicate that it is feasible to use L. lactis as an antigen delivery vehicle in developing oral vaccines against IBV infection.


title: Expression and immunogenicity of the spike glycoprotein of porcine respiratory coronavirus encoded in the E3 region of adenovirus.

text: The full length spike (S) gene of porcine respiratory coronavirus (PRCV) was inserted into the genome of human adenovirus type 5 downstream of the early transcription region 3 promoter. The recombinant virus replicated in cultures of the swine testicle ST cell line and directed the synthesis of S antigen to an amount of approximately 33 micrograms per 10(6) cells, as determined by ELISA. The antigen was cell-associated except in the late phase of the infection, when a low amount (4 micrograms per 10(6) cells) was released in the culture supernatant. The cell-associated antigen consisted of 2 polypeptides of 160 K and 175 K, respectively. The 160 K polypeptide comigrated with the authentic S' precursor from PRCV-infected cells. The 175 K polypeptide had the same mobility as the authentic mature S protein from PRCV-infected cells and from PRCV released in the supernatant. The extracellular recombinant antigen corresponded with the 175 K mature protein. Immunofluorescent staining gave evidence that some recombinant S protein was exposed on the cell surface; it also showed that the protein was recognized by conformation-specific anti-S monoclonal antibodies. Piglets, immunized oronasally with the recombinant adenovirus vector developed PRCV-neutralizing serum antibodies and were partially protected against PRCV-challenge.


Fragmentation and rearrangement of the Golgi apparatus during MHV infection of L-2 cells.


title: Biogenesis of the Semliki Forest virus RNA replication complex.

text: The nonstructural (ns) proteins nsP1 to -4, the components of Semliki Forest virus (SFV) RNA polymerase, were localized in infected cells by confocal microscopy using double labeling with specific antisera against the individual ns proteins. All ns proteins were associated with large cytoplasmic vacuoles (CPV), the inner surfaces of which were covered by small invaginations, or spherules, typical of alphavirus infection. All ns proteins were localized by immuno-electron microscopy (EM) to the limiting membranes of CPV and to the spherules, together with newly labeled viral RNA. Along with earlier observations by EM-autoradiography (P. M. Grimley, I. K. Berezesky, and R. M. Friedman, J. Virol. 2:326-338, 1968), these results suggest that individual spherules represent template-associated RNA polymerase complexes. Immunoprecipitation of radiolabeled ns proteins showed that each antiserum precipitated the other three ns proteins, implying that they functioned as a complex. Double labeling with organelle-specific and anti-ns-protein antisera showed that CPV were derivatives of late endosomes and lysosomes. Indeed, CPV frequently contained endocytosed bovine serum albumin-coated gold particles, introduced into the medium at different times after infection. With time, increasing numbers of spherules were also observed on the cell surfaces; they were occasionally released into the medium, probably by secretory lysosomes. We suggest that the spherules arise by primary assembly of the RNA replication complexes at the plasma membrane, guided there by nsP1, which has affinity to lipids specific for the cytoplasmic leaflet of the plasma membrane. Endosomal recycling and fusion of CPV with the plasma membrane can circulate spherules between the plasma membrane and the endosomal-lysosomal compartment.


title: Virome analysis for identification of novel mammalian viruses in bat species from Chinese provinces.

text: Bats are natural hosts for a large variety of zoonotic viruses. This study aimed to describe the range of bat viromes, including viruses from mammals, insects, fungi, plants, and phages, in 11 insectivorous bat species (216 bats in total) common in six provinces of China. To analyze viromes, we used sequence-independent PCR amplification and next-generation sequencing technology (Solexa Genome Analyzer II; Illumina). The viromes were identified by sequence similarity comparisons to known viruses. The mammalian viruses included those of the Adenoviridae, Herpesviridae, Papillomaviridae, Retroviridae, Circoviridae, Rhabdoviridae, Astroviridae, Flaviridae, Coronaviridae, Picornaviridae, and Parvovirinae; insect viruses included those of the Baculoviridae, Iflaviridae, Dicistroviridae, Tetraviridae, and Densovirinae; fungal viruses included those of the Chrysoviridae, Hypoviridae, Partitiviridae, and Totiviridae; and phages included those of the Caudovirales, Inoviridae, and Microviridae and unclassified phages. In addition to the viruses and phages associated with the insects, plants, and bacterial flora related to the diet and habitation of bats, we identified the complete or partial genome sequences of 13 novel mammalian viruses. These included herpesviruses, papillomaviruses, a circovirus, a bocavirus, picornaviruses, a pestivirus, and a foamy virus. Pairwise alignments and phylogenetic analyses indicated that these novel viruses showed little genetic similarity with previously reported viruses. This study also revealed a high prevalence and diversity of bat astroviruses and coronaviruses in some provinces. These findings have expanded our understanding of the viromes of bats in China and hinted at the presence of a large variety of unknown mammalian viruses in many common bat species of mainland China.


title: A new self: MHC-class-I-independent natural-killer-cell self-tolerance.

text: A fundamental tenet of the immune system is the requirement for lymphocytes to respond to transformed or infected cells while remaining tolerant of normal cells. Natural killer (NK) cells discriminate between self and non-self by monitoring the expression of MHC class I molecules. According to the 'missing-self' hypothesis, cells that express self-MHC class I molecules are protected from NK cells, but those that lack this self-marker are eliminated by NK cells. Recent work has revealed that there is another system of NK-cell inhibition, which is independent of MHC class I molecules. Newly discovered NK-cell inhibitory receptors that have non-MHC-molecule ligands broaden the definition of self as seen by NK cells.


title: Pandemic threats and the need for new emergency public health legislation in Canada.

text: The 2003 outbreak of Severe Acute Respiratory Syndrome (SARS) exposed serious limitations in Canada's ability to respond to a public health emergency. Considerable progress has been made since SARS in addressing these limitations, including the creation of the new Public Health Agency of Canada. A remaining contentious question is whether there is a need for new federal emergency public health powers. Approaches to public health problems are best handled through collaborative processes, recognizing the critical importance of the local public health response. Nevertheless, this paper argues that a legislative back-up plan must be available to the federal government in the event that collaborative relationships break down. At the minimum, legislation should give the federal government the authority to have guaranteed access to surveillance data during a public health emergency. The legislation should also consider providing the federal government with the authority to devote the nation's resources to the management of an emergency at its earliest stages. However, any legislative approach must be combined with the development of appropriate capacity at the national level to ensure that new powers can be adequately utilized and that required funding reaches public health officials at other levels of government.


title: Lack of CCR2 results in increased mortality and impaired leukocyte activation and trafficking following infection of the central nervous system with a neurotropic coronavirus.

text: In the present study, we evaluated the role of CCR2 in a model of viral-induced neurologic disease. An orchestrated expression of chemokines, including the CCR2 ligands monocyte chemoattractant protein-1/CCL2 and monocyte chemoattractant protein-3/CCL7, occurs within the CNS following infection with mouse hepatitis virus (MHV). Infection of mice lacking CCR2 (CCR2(-/-)) with MHV resulted in increased mortality and enhanced viral recovery from the brain that correlated with reduced (p < or = 0.04) T cell and macrophage/microglial (determined by F4/80 Ag expression, p < or = 0.004) infiltration into the CNS. Moreover, MHV-infected CCR2(-/-) mice displayed a significant decrease in Th1-associated factors IFN-gamma (p < or = 0.001) and RANTES/CCL5 (p < or = 0.002) within the CNS as compared with CCR2(+/+) mice. Further, peripheral CD4(+) and CD8(+) T cells from immunized CCR2(-/-) mice displayed a marked reduction in IFN-gamma production in response to viral Ag and did not migrate into the CNS of MHV-infected recombination-activating gene (RAG)1(-/-) mice following adoptive transfer. In addition, macrophage/microglial infiltration into the CNS of RAG1(-/-) mice receiving CCR2(-/-) splenocytes was reduced (p < or = 0.05), which correlated with a reduction in the severity of demyelination (p < or = 0.001) as compared with RAG1(-/-) mice receiving splenocytes from CCR2(+/+) mice. Collectively, these results indicate an important role for CCR2 in host defense and disease by regulating leukocyte activation and trafficking.


title: Chronic pulmonary disease in West Highland white terriers.

text: This paper describes the clinical features, and diagnostic findings of a chronic respiratory condition in 29 West Highland white terriers. Typically, the dogs were coughing chronically, had dyspnoea and tachypnoea of varying severity, and had deteriorated progressively over months to years. The mean (sem) survival time in months from the clinical signs being first noted by the owners was 17.9 (2.3). Most cases had a combination of respiratory signs, but coughing was the predominant sign in 18 cases. Inspiratory crackles were audible on chest auscultation in 28 cases, 10 of which were also wheezing. Rhonchi were the predominant sound in the remaining case. The main radiographic changes were mild to severe increased Interstitial markings in all cases, with additional bronchial markings in 14 of the dogs. Right-sided cardiomegaly (cor pulmonale) was recorded in 15. Bronchoscopic findings in 17 of the dogs were either normal or involved a mild airway mucoid reaction in eight. Chronic mucosal changes were observed in eight, but in two this finding was equivocal. Dynamic changes to the lumen of the airway were present in seven cases. No significant haematological or biochemical changes could be detected in 20 cases, but four cases were hypercholestrolaemic. A histopathological assessment of four cases revealed alveolar septal fibrosis to be the predominant change. Prednisolone, with or without bronchodilators, was the most commonly used therapy, and the response was variable. The condition appears to be associated with significant pulmonary interstitial fibrosis of unknown aetiology and has clinical similarities to idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis) in human beings.


title: Exercise training in patients receiving maintenance hemodialysis: a systematic review of clinical trials.

text: BACKGROUND Exercise is not routinely advocated in patients with end-stage renal disease (ESRD) receiving maintenance hemodialysis (HD), compared to best practice in other chronically diseased cohorts. Lack of widespread awareness of the exercise in HD literature may be contributing to these shortcomings of clinical practice. Therefore, our objectives are: (1) to systematically review trials of exercise training involving adult HD patients; (2) to provide empirical evidence that exercise can elicit health-related adaptations in this cohort, and (3) to provide recommendations for future investigations. METHOD A systematic review of the literature using computerized databases was performed. RESULTS According to the 29 trials reviewed, HD patients can safely derive a myriad of health-related adaptations from engaging in appropriately structured exercise regimens involving aerobic and/or resistance training. However, methodological limitations within this body of literature may be partially responsible for minimal advocacy for exercise in this cohort. CONCLUSIONS Robustly designed RCTs with thorough, standardized reporting are required if clinical practice and quality of life of this cohort is to be enhanced through the integration of exercise training and mainstream medical practice. Future trials should demonstrate the clinical importance, and long-term feasibility and applicability of exercise training for this vulnerable patient population.


Receptor specificity and receptor-induced conformational changes in mouse hepatitis virus spike glycoprotein.


title: Nurses sacrificed their lives in SARS outbreak.

text: NURSES PUT their lives on the line caring for people during the Severe Acute Respiratory Syndrome (SARS) epidemic earlier this year, the International Council of Nurses (ICN) biennial congress in Geneva was told.


title: Effect-site concentration of remifentanil for preventing cough during emergence in elderly patients undergoing nasal surgery: a comparison with adult patients.

text: PURPOSE Prevention of cough during emergence after nasal surgery is important for avoiding surgical site bleeding. We investigated the remifentanil effect-site concentration in 50% (EC50) of the elderly patients undergoing nasal surgery for smooth emergence without cough and compared it with that of adult patients. METHODS Twenty-two elderly (aged 65-80 years) and 25 adult patients (aged 20-60 years) with an American Society of Anesthesiologists physical status I/II undergoing nasal surgery were enrolled. Anesthesia was maintained with sevoflurane and remifentanil. Remifentanil EC50 and EC95 for preventing cough were determined using the modified Dixon's up-and-down method and isotonic regression with bootstrapping approach. Recovery profiles were also recorded. RESULTS With Dixon's up-and-down method, the EC50 of remifentanil in elderly patients (2.40±0.25 ng/mL) was not significantly different from that of adults (2.33±0.30 ng/mL) (P=0.687). With isotonic regression, the EC95 of remifentanil in elderly patients (3.32 [95% confidence interval: 3.06-3.38] ng/mL) was not significantly different from that of adults (3.30 [95% confidence interval: 2.96-3.37] ng/mL). However, eye opening time (14.1±3.8 vs 12.0±2.9 seconds), extubation time (17.2±4.1 vs 14.0±3.0 seconds), and postanesthesia care unit duration (44.5±7.6 vs 38.7±3.4 minutes) in elderly patients were significantly longer than those in adults (P<0.05). CONCLUSION Remifentanil EC50 for preventing cough after nasal surgery with sevoflurane anesthesia did not differ between elderly and adult patients. However, delayed awakening and respiratory adverse events may warrant attention in elderly patients.


title: Historical Data Analysis of Hospital Discharges Related to the Amerithrax Attack in Florida.

text: Interrupted time-series analysis (ITSA) can be used to identify, quantify, and evaluate the magnitude and direction of an event on the basis of time-series data. This study evaluates the impact of the bioterrorist anthrax attacks ("Amerithrax") on hospital inpatient discharges in the metropolitan statistical area of Palm Beach, Broward, and Miami-Dade counties in the fourth quarter of 2001. Three statistical methods-standardized incidence ratio (SIR), segmented regression, and an autoregressive integrated moving average (ARIMA)-were used to determine whether Amerithrax influenced inpatient utilization. The SIR found a non-statistically significant 2 percent decrease in hospital discharges. Although the segmented regression test found a slight increase in the discharge rate during the fourth quarter, it was also not statistically significant; therefore, it could not be attributed to Amerithrax. Segmented regression diagnostics preparing for ARIMA indicated that the quarterly data time frame was not serially correlated and violated one of the assumptions for the use of the ARIMA method and therefore could not properly evaluate the impact on the time-series data. Lack of data granularity of the time frames hindered the successful evaluation of the impact by the three analytic methods. This study demonstrates that the granularity of the data points is as important as the number of data points in a time series. ITSA is important for the ability to evaluate the impact that any hazard may have on inpatient utilization. Knowledge of hospital utilization patterns during disasters offer healthcare and civic professionals valuable information to plan, respond, mitigate, and evaluate any outcomes stemming from biothreats.


title: Quadriceps tendon tear rupture in healthy patients treated with patellar drilling holes: clinical and ultrasonographic analysis after 36 months of follow-up.

text: BACKGROUND quadriceps tendon subcutaneous rupture is an uncommon injury affecting predominantly middle-aged men as a result of direct or indirect trauma; aim of this work is to evaluate clinical outcome and tendon morphology in patients treated surgically with transpatellar drilling suture. METHODS 20 patients (20 male) with an average age of 54 (42-59) were evaluated with a mean follow-up of 36 months. Measurements of range of motion (ROM) and of tight circumference were collected. Lysholm and Rougraff Score were also performed. All the patients underwent a US evaluation the morphologic changes of the repaired tendon. RESULTS mean active ROM was 1°-117°; average difference in the circumference of the quadriceps was 2.6% 10 C and 3.3% 15 C. The mean Lysholm Score calculated was 88/100; the mean Rougraff Score 17/25. At ultrasonographic evaluation all tendons were continuous; heterotopic ossification was present in 18 quadriceps tendons. Thickness was augmented in 18 quadriceps tendons and in 5 patellar tendons. Vascularization was always conserved. Lateral subluxation of patella was reported in 1 case. CONCLUSIONS patellar drilling holes repair is a non-demanding procedure, inexpensive and technically uncomplicated. US evaluation confirms tendon healing; tendon remodeling does not affect patient's clinical outcome and quality of life. LEVEL OF INCIDENCE IV.


title: [Role of mass media during the severe acute respiratory syndrome epidemic].

text: OBJECTIVE To understand the impact of effective interaction between public and media on the prevention and control of severe acute respiratory syndrome (SARS). METHODS Based on the theory of field epidemiology, the traditional and modern technologies were brought forward. In the late period of SARS epidemic, investigation on knowledge, attitude and practice on SARS prevention and control among general population was conducted. RESULTS During the 3 month period of SARS epidemic in Shenzhen, techniques of the "E-health and public health informatics" as an emerging fields were used to focus on population to eventually improve the health of entire population. Methods as television, radio, newspapers, magazines, printing and distribution of specific materials on SARS were included, and hotlines of telephone and mobile phone, web-based sites, electronic screening advertisements, and consultation or forum for the public etc. were used. Among 3405 subjects interviewed, more than 95% gave right answers on the SARS related questions. Most of them held the optimistic and scientific attitude. 80% of the population had taken the measures as recommended. 82.4% of the citizens were happy about the local government's action and 93.8% thought hospitals and healthcare workers should be respected and honored. CONCLUSION Dealing with the urgent public health problems and emerging infectious diseases outbreak, epidemiologists need to keep good relations with media, and making use of modern electronic technologies to communicate with the public.


Applications of Traditional Chinese Medicine in Antiviral and Anticancer Drug Development: An Interview with Dr. Yung-Chi (Tommy) Cheng, PhD.


title: Uncertain benefit: the public policy of approving smallpox vaccine research.

text: Without an accurate assessment of the prospect of bioterrorist attack, it is especially challenging to evaluate the protocols for testing smallpox vaccines in the pediatric population. Usual regulatory mechanisms cannot shepherd research protocols with benefits that can only be characterized as "uncertain" in the face of more than minimal risk. When a protocol is placed in a government forum for analysis, the public has a unique opportunity to debate the balancing of research risks and benefits on behalf of children who are unable to assent to research themselves, as well as to express views about vaccination policy broadly. This model for review of pediatric research that may be without benefit will be especially important as challenging studies of various vaccines against a range of infectious properties, such as anthrax and severe acute respiratory syndrome (SARS), emerge.


title: A novel severe acute respiratory syndrome coronavirus protein, U274, is transported to the cell surface and undergoes endocytosis.

text: The severe acute respiratory syndrome coronavirus (SARS-CoV) genome contains open reading frames (ORFs) that encode for several genes that are homologous to proteins found in all known coronaviruses. These are the replicase gene 1a/1b and the four structural proteins, nucleocapsid (N), spike (S), membrane (M), and envelope (E), and these proteins are expected to be essential for the replication of the virus. In addition, this genome also contains nine other potential ORFs varying in length from 39 to 274 amino acids. The largest among these is the first ORF of the second longest subgenomic RNA, and this protein (termed U274 in the present study) consists of 274 amino acids and contains three putative transmembrane domains. Using antibody specific for the C terminus of U274, we show U274 to be expressed in SARS-CoV-infected Vero E6 cells and, in addition to the full-length protein, two other processed forms were also detected. By indirect immunofluorescence, U274 was localized to the perinuclear region, as well as to the plasma membrane, in both transfected and infected cells. Using an N terminus myc-tagged U274, the topology of U274 and its expression on the cell surface were confirmed. Deletion of a cytoplasmic domain of U274, which contains Yxxphi and diacidic motifs, abolished its transport to the cell surface. In addition, U274 expressed on the cell surface can internalize antibodies from the culture medium into the cells. Coimmunoprecipitation experiments also showed that U274 could interact specifically with the M, E, and S structural proteins, as well as with U122, another protein that is unique to SARS-CoV.


title: Retention of specific yolk IgY in the human oral cavity.

text: INTRODUCTION The increasing prevalence of antibiotic-resistant bacteria emphasises the need for new treatments that can replace traditional antibiotics. Oral immunotherapy with yolk antibodies from hyperimmunised hens is a new promising treatment strategy, primarily for infections in the mouth and gastrointestinal tract. Several studies show that bacterial and viral infections can be prevented with egg yolk immunoglobulin (IgY) in a dose-dependent manner. Oral treatment could potentially be used against many frequently encountered diseases (e.g. common cold, tonsillitis and caries). GROUP STUDIED: Healthy volunteers. STUDY DESIGN We studied the presence of yolk anti-Pseudomonas aeruginosa antibodies in saliva from healthy volunteers over time after 1 or 2 minutes' mouth rinse, performed in the evening, with an aqueous IgY antibody preparation. The test persons rinsed the mouth with 8.0ml phosphate buffered saline before gargling with the antibody preparation 8 and 24 hours later. Statistical analysis was performed with the Mann-Whitney U test. METHODS The antibody titres in the mouth rinses were tested for their specific activity against P. aeruginosa by ELISA. RESULTS AND CONCLUSION The next morning there were still active antibodies detected in the saliva from 18 of 19 subjects. After 24 hours, active antibodies could be detected in saliva from only a few of the subjects. A 2-minute mouth rinse resulted in higher mean ELISA absorbance values than a 1-minute rinse.


title: Role of enteric pathogens in the aetiology of neonatal diarrhoea in lambs and goat kids in Spain.

text: Faeces samples from diarrhoeic and non-diarrhoeic lambs and goat kids aged 1-45 days were examined for enteric pathogens. Cryptosporidium parvum was detected in both diarrhoeic lambs (45%) and goat kids (42%) but not in non-diarrhoeic animals. F5+ (K99+) and/or F41+ Escherichia coli strains were isolated from 26% and 22% of the diarrhoeic lambs and goat kids, respectively, although these strains, which did not produce enterotoxins ST I or LT I, were found with similar frequencies in non-diarrhoeic animals. A F5-F41-ST I+ E. coli strain was isolated from a diarrhoeic lamb (0.6%). Verotoxigenic E. coli was isolated from both diarrhoeic and non-diarrhoeic lambs (4.1% and 8.2%, respectively) and there was no association between infection and diarrhoea. The prevalence of group A rotavirus infection in diarrhoeic lambs was very low (2.1%). Groups A and B rotaviruses were detected in three (8.1%) and five (13.5%) diarrhoeic goat kids from two single outbreaks. Group C rotaviruses were detected in four non-diarrhoeic goat kids. An association of diarrhoea and infection was demonstrated only for group B rotavirus. Clostridium perfringens was isolated from 10.8% of the diarrhoeic goat kids but not from non-diarrhoeic goat kids or lambs. Salmonella arizonae was isolated from a diarrhoeic goat kid (2.7%) and the clinical characteristics of the outbreaks where these two latter enteropathogens were found different from the rest. Picobirnaviruses were detected in a diarrhoeic lamb. No coronaviruses were detected using a bovine coronavirus ELISA. No evidence was found of synergistic effect between the agents studied. Enteric pathogens were not found in four (8.7%) and three (20%) outbreaks of diarrhoea in lambs and goat kids, respectively.


title: If schools are closed, who will watch our kids? Family caregiving and other sources of role conflict among nurses during large-scale outbreaks.

text: OBJECTIVES The global impact of severe acute respiratory syndrome (SARS) brought attention to the role of healthcare professionals as "first receivers" during infectious disease outbreaks, a collateral aspect to their role as responders. This article records and reports concerns expressed by Canadian emergency and critical care nurses in terms of organizational and social supports required during infectious disease outbreaks. The nature of work-family and family-work conflict perceived and experienced by nurses during infectious disease outbreaks, as well as the supports needed to enable them to balance their social roles during this type of heightened stress, are explored. METHODS Five focus groups consisting of 100 nurses were conducted using a Structured Interview Matrix facilitation technique. RESULTS Four emergent themes included: (1) substantial personal/professional dilemmas; (2) assistance with child, elder, and/or pet care; (3) adequate resources and vaccinations to protect families; and (4) appropriate mechanisms to enable two-way communication between employees and their families under conditions of quarantine or long work hours. CONCLUSIONS Social and organizational supports are critical to help buffer the effects of stress for nurses and assist them in managing difficult role conflicts during infectious disease outbreaks. These supports are necessary to improve response capacity for bio-disasters.


title: Viral agents associated with outbreaks of diarrhea in turkey flocks in Quebec.

text: The relative importance of various enteric viruses associated with diarrhea of turkey poults was investigated by an evaluation of specimens received since 1982. Specimens originated from one to eight week old turkey poults, with mild to severe diarrhea, from 114 flocks in 42 commercial operations located in southern Quebec. The acute phase of enteritis occurred usually in poults between two and four weeks of age. Clarified intestinal contents were examined by direct electron microscopy and enzyme immunoassays. Enzyme-linked immunosorbent assays were performed with antisera to bovine rotavirus group antigen, avian reovirus types 1 to 5, and the prototype strain of the turkey enteric coronavirus. The presence of viruses could be demonstrated by electron microscopy in 55.3% of the specimens, and at least five different viruses were incriminated either alone or in combination. The coronavirus was by far the most common enteric virus with a prevalence of 47.5%. By enzyme-linked immunosorbent assay, rotavirus, reovirus and turkey coronavirus were detected in 14.5%, 18.1% and 61.4% of the specimens, respectively. By electron microscopy, 56.6% of these cases were positive for at least one virus.


title: Relation between immune variables and burnout in a sample of physicians.

text: OBJECTIVES To evaluate in a group of physicians the relation between burnout, demographic or job characteristics, anxiety, and immune variables. METHODS Seventy one physicians of all grades were recruited among different departments to a cross sectional survey. The Maslach burnout inventory, scales of emotional exhaustion, depersonalisation, and personal accomplishment, the trait scale of anxiety inventory (STAI-Y2), and a questionnaire on personal and professional characteristics were administered. The immune profile included quantitative (number (%) of lymphocytes and subsets) and functional (natural killer cytotoxicity) measures. RESULTS With a model of stepwise multiple regression analysis, emotional exhaustion was significantly affected by both personal (marital, sex) and job characteristics (qualification, working activity), whereas only patient contact explained a portion of variation in depersonalisation. Furthermore, trait anxiety was found to predict the Maslach burnout inventory scores. After correction for potential confounders, physicians who scored high levels of personal accomplishment showed significantly higher numbers of total lymphocytes, T cells (CD3), T helper cells (CD4), and T suppressor cells (CD8) than those who scored low levels. No other correlation was found between burnout and immune variables. CONCLUSIONS In our group of relatively young physicians a high degree of personal accomplishment was associated with an increase in the number of peripheral lymphocytes, particularly T subsets. The meaning of this is not clear, although it could be speculated that to evaluate oneself positively, particularly with regard to work with patients in the health services, might help to stimulate the immune system. By contrast, there is no evidence that to work hard, to feel tired from work, and to have a cynical reaction towards patient care is related to immunosuppression.


title: Antibodies to canine and feline viruses in spotted hyenas (Crocuta crocuta) in the Masai Mara National Reserve.

text: Spotted hyenas (Crocuta crocuta) are abundant predators in the Serengeti ecosystem and interact with other species of wild carnivores and domestic animals in ways that could encourage disease transmission. Hyenas also have a unique hierarchical social system that might affect the flow of pathogens. Antibodies to canine distemper virus (CDV), feline immunodeficiency virus (FIV), feline panleukopenia virus/canine parvovirus (FPLV/CPV), feline coronavirus/ feline infectious peritonitis virus (FECV/IPV), feline calicivirus (FCV), and feline herpesvirus 1 (FHV1) have been detected in other Serengeti predators, indicating that these viruses are present in the ecosystem. The purpose of this study was to determine whether spotted hyenas also had been infected with these viruses and to assess risk factors for infection. Serum samples were collected between 1993 and 2001 from 119 animals in a single clan for which behavioral data on social structure were available and from 121 hyenas ill several other clans. All animals resided in the Masai Mara National Reserve. Antibodies to CDV, FIV, FPLV/CPV, FECV/FIPV, FCV, and FHV1 were present in 47%, 3.5%, 81%, 36%, 72%, and 0.5% of study hyenas, respectively. Antibody prevalence was greater in adults for FIV and FECV/FIPV, and being a female of high social rank was a risk factor for FIV. Hyenas near human habitation appeared to be at lower risk to have CDV, FIV, and FECV/FIPV antibodies, whereas being near human habitation increased the risk for FPLV/CPV antibodies. Canine (distemper virus and FECV/FIPV antibody prevalence varied considerably over time, whereas FIV, FPLV/CPV, and FCV had a stable, apparently endemic temporal pattern. These results indicate that hyenas might play a role in the ecology of these viruses in the Serengeti ecosystem. The effect of these viruses on hyena health should be further investigated. The lower prevalence of CDV antibody-positive hyenas near human habitation suggests that reservoirs for CDV other than domestic dogs are present in the Serengeti ecosystem.


title: Epigenetics in Developmental Disorder: ADHD and Endophenotypes.

text: Heterogeneity in attention-deficit/hyperactivity disorder (ADHD), with complex interactive operations of genetic and environmental factors, is expressed in a variety of disorder manifestations: severity, co-morbidities of symptoms, and the effects of genes on phenotypes. Neurodevelopmental influences of genomic imprinting have set the stage for the structural-physiological variations that modulate the cognitive, affective, and pathophysiological domains of ADHD. The relative contributions of genetic and environmental factors provide rapidly proliferating insights into the developmental trajectory of the condition, both structurally and functionally. Parent-of-origin effects seem to support the notion that genetic risks for disease process debut often interact with the social environment, i.e., the parental environment in infants and young children. The notion of endophenotypes, markers of an underlying liability to the disorder, may facilitate detection of genetic risks relative to a complex clinical disorder. Simple genetic association has proven insufficient to explain the spectrum of ADHD. At a primary level of analysis, the consideration of epigenetic regulation of brain signalling mechanisms, dopamine, serotonin, and noradrenaline is examined. Neurotrophic factors that participate in the neurogenesis, survival, and functional maintenance of brain systems, are involved in neuroplasticity alterations underlying brain disorders, and are implicated in the genetic predisposition to ADHD, but not obviously, nor in a simple or straightforward fashion. In the context of intervention, genetic linkage studies of ADHD pharmacological intervention have demonstrated that associations have fitted the "drug response phenotype," rather than the disorder diagnosis. Despite conflicting evidence for the existence, or not, of genetic associations between disorder diagnosis and genes regulating the structure and function of neurotransmitters and brain-derived neurotrophic factor (BDNF), associations between symptoms-profiles endophenotypes and single nucleotide polymorphisms appear reassuring.


Heat wave triggers political conflict as French death rates rise.


title: The papain-like protease from the severe acute respiratory syndrome coronavirus is a deubiquitinating enzyme.

text: The severe acute respiratory syndrome coronavirus papain-like protease (SARS-CoV PLpro) is involved in the processing of the viral polyprotein and, thereby, contributes to the biogenesis of the virus replication complex. Structural bioinformatics has revealed a relationship for the SARS-CoV PLpro to herpesvirus-associated ubiquitin-specific protease (HAUSP), a ubiquitin-specific protease, indicating potential deubiquitinating activity in addition to its function in polyprotein processing (T. Sulea, H. A. Lindner, E. O. Purisima, and R. Menard, J. Virol. 79:4550-4551, 2005). In order to confirm this prediction, we overexpressed and purified SARS-CoV PLpro (amino acids [aa]1507 to 1858) from Escherichia coli. The purified enzyme hydrolyzed ubiquitin-7-amino-4-methylcoumarin (Ub-AMC), a general deubiquitinating enzyme substrate, with a catalytic efficiency of 13,100 M(-1)s(-1), 220-fold more efficiently than the small synthetic peptide substrate Z-LRGG-AMC, which incorporates the C-terminal four residues of ubiquitin. In addition, SARS-CoV PLpro was inhibited by the specific deubiquitinating enzyme inhibitor ubiquitin aldehyde, with an inhibition constant of 210 nM. The purified SARS-CoV PLpro disassembles branched polyubiquitin chains with lengths of two to seven (Ub2-7) or four (Ub4) units, which involves isopeptide bond cleavage. SARS-CoV PLpro processing activity was also detected against a protein fused to the C terminus of the ubiquitin-like modifier ISG15, both in vitro using the purified enzyme and in HeLa cells by coexpression with SARS-CoV PLpro (aa 1198 to 2009). These results clearly establish that SARS-CoV PLpro is a deubiquitinating enzyme, thereby confirming our earlier prediction. This unexpected activity for a coronavirus papain-like protease suggests a novel viral strategy to modulate the host cell ubiquitination machinery to its advantage.


title: Viral inhibitors of NKG2D ligands for tumor surveillance.

text: INTRODUCTION Natural Killer cells (NK) are key for the innate immune response against tumors and viral infections. Several viral proteins evade host immune response and target the NK cell receptor NKG2D and its ligands. Areas covered: This review aimed to describe the viruses and their proteins that interfere with the NKG2D receptor and their ligands, and how these interactions lead to immune evasion, host protection, and tissue damage from acute and chronic viral infections. Expert opinion: The study of viral proteins has already impacted the field of oncology. A prime example is the HBV vaccine and the development of antiviral drugs for HIV, Hepatitis C, and the family of Herpesviridae viruses. The NKG2D system seems to be a rational therapeutic target. Nevertheless, an effective cytotoxic response by NK cells is mediated by a network of activating and inhibitory receptors, the integration of which determines if the NK cell becomes cytotoxic or permissive. Immunotherapeutic agents that increase the antitumor lytic activity of NK cells through modulating activation and inhibitory signaling of NK cells are being developed. Nevertheless, more research is needed to dissect the integrative mechanism of NK cells function to fully exploit their antitumor and antiviral effector mechanisms.


title: Enteric viruses associated with HIV infection in Tanzanian children with chronic diarrhea.

text: OBJECTIVE To determine whether specific viruses are associated with HIV infection in Tanzanian children with chronic diarrhea. DESIGN Cross-sectional survey. SETTING Major national teaching hospital in Dar es Salaam, Tanzania. PATIENTS Consecutively admitted, human immunodeficiency virus (HIV)-infected and HIV-uninfected children with chronic diarrhea, and controls without diarrhea, aged 15 months to 5 years. MAIN OUTCOME MEASURE Enteric viruses identified by electron microscopy (EM) of fecal specimens. RESULTS Small round structured viruses (SRSV) were more frequent in HIV-infected than HIV-uninfected children with chronic diarrhea (4 of 21 vs 1 of 32, prevalence ratio = 6.09, 90% confidence limits 1.03, 36.14). Rotavirus and coronavirus-like particles (CVLP) were not associated with HIV infection. CONCLUSION SRSV may be associated with HIV infection in Tanzanian children with chronic diarrhea. Larger, confirmatory studies are needed.


title: Managing a mammography center: a model to thrive.

text: BACKGROUND With the ever-increasing burdens of adhering to the Mammography Quality Standards Act (MQSA), it is important for mammography centers to use technology to work smarter and faster and capture as much revenue as possible. At the same time, patient satisfaction and employee satisfaction have a synergistic effect on the quality of patient care and the financial status of the clinic. METHOD This comprehensive literature review examines the effects of MQSA, technology and patient and employee satisfaction on the operations of a quality breast imaging center. RESULTS A best practice model is offered that combines the best of these elements based on current literature.


title: Influenza as a model system for studying the cross-species transfer and evolution of the SARS coronavirus.

text: Severe acute respiratory syndrome coronavirus (SARS-CoV) moved into humans from a reservoir species and subsequently caused an epidemic in its new host. We know little about the processes that allowed the cross-species transfer of this previously unknown virus. I discuss what we have learned about the movement of viruses into humans from studies of influenza A, both how it crossed from birds to humans and how it subsequently evolved within the human population. Starting with a brief review of severe acute respiratory syndrome to highlight the kinds of problems we face in learning about this viral disease, I then turn to influenza A, focusing on three topics. First, I present a reanalysis of data used to test the hypothesis that swine served as a "mixing vessel" or intermediate host in the transmission of avian influenza to humans during the 1918 "Spanish flu" pandemic. Second, I review studies of archived viruses from the three recent influenza pandemics. Third, I discuss current limitations in using molecular data to study the evolution of infectious disease. Although influenza A and SARS-CoV differ in many ways, our knowledge of influenza A may provide important clues about what limits or favours cross-species transfers and subsequent epidemics of newly emerging pathogens.


title: Coronavirus IBV: relationships among recent European isolates studied by limited proteolysis of the virion glycopolypeptides.

text: After the year 1978, strains of avian infectious bronchitis virus (IBV) were isolated in the Netherlands and the UK which were assigned by neutralisation tests to four new serotypes (arbitrarily designated A, B, C and D in this communication) distinct from the long recognised US serotypes. We have labelled, with 35S-methionine, the structural polypeptides of 12 of the European isolates during growth in de-embryonated eggs. The S2, spike-anchoring, polypeptide of isolates of all four serotypes had a molecular weight of 87 000 (87K) whereas the US IBV-M41 strain had S2 of 84K. When the isolates were grouped according to the molecular weight of the other spike glycopolypeptide, S1, and the membrane (M) glycopolypeptide four groups emerged which corresponded to the serotypes based on neutralisation tests. Serotypes A (isolates D207, 1, 5 and 6) and B (isolates 7, 8 and D3896) had S1 of 91.5K while serotypes C (isolates 9 and D3128) and D (isolates D212 and D1466) had S1 of 90K. The M of serotypes A and D had a molecular weight of 30K while that of serotypes B and C was 27K. Chymotrypsin and protease V8 were used for limited proteolysis, the hydrolysis of S1 giving the greatest discrimination between serotypes. After proteolysis of S1 the UK isolates of serotype A gave identical profiles which were very similar to the Dutch serotype A isolate D207. Isolates of serotype B gave S1 profiles very similar to those of serotype A, as did D274 which is serologically related to both groups A and B. Serotypes C and D were distinguishable from each other and from serotypes A and B on the basis of the S1 peptide profiles. These results strengthen the view that the UK and Dutch isolates are closely related and that serotypes A and B are more closely related to each other than to either group C or D serotypes.


Hepatitis C virus (HCV) genotypes and disease progression in HIV/HCV-coinfected patients.


title: Robotic Transhiatal Esophagectomy in a Community Hospital: Evolution of Technique.

text: Esophageal cancer is an uncommon but highly lethal disease. Surgical resection is the gold standard of treatment for early-stage disease. Traditional surgical approach entailed significant convalescence, hospital stay, and morbidity and mortality. Transhiatal esophagectomy (THE) involves blind dissection of the esophagus with minimal mediastinal lymphadenectomy. Integration of robotic surgery is an alternate platform for minimally invasive approach while maintaining safety and following oncologic principles. We review our technique for minimally invasive THE using robotic technology, demonstrating the safety and efficacy of robotic technology surgery. We present a retrospective review of a single surgeon's data of patients treated with robotic-assisted THE, with a chart review to evaluate pathology, adequacy of surgical resection, nodal harvest, and perioperative course. Robotic THE (rTHE) shows promise as a valid option for esophageal resection, including premalignant and advanced stages of cancer. Adequate transhiatal mediastinal nodal resection can be performed with the robot.


title: Colour-coded duplex sonography of the testes of dogs.

text: Colour-coded duplex sonography was used to examine the testes of 42 dogs whose testes were normal on clinical examination. With colour Doppler, the blood flow in the supratesticular region could be displayed clearly in 70 per cent of the cases, independent of the dog's age, bodyweight, pulse rate and the volume of its testes. The marginal artery could be displayed clearly in 56 per cent of the cases, and the clarity was correlated with bodyweight (P<0.001), testicular volume (P<0.001), and pulse rate (P<0.001). The intratesticular blood flow could not be discerned in 42 per cent of the cases. With pulsed Doppler, the mean resistive index (RI) in the supratesticular region was 0.57, and the mean pulsatility index (PI) was 1.00. In the marginal artery, the mean RI was 0.49, and mean PI was 0.78. In the intratesticular arteries, the mean RI was 0.47, and the mean PI was 0.75. At all three sites both indices were independent of age, bodyweight, pulse rate and testicular volume.


title: Isolation and characterization of a coronavirus from pigeons with pancreatitis.

text: OBJECTIVE To identify and partially characterize a coronaviruslike virus isolated from naturally infected pigeons. ANIMALS 50 specific pathogen-free (SPF) embryonated chicken eggs, 30 White Leghorn SPF chickens, and 12 clinically normal pigeons. PROCEDURES Pancreatic tissue specimens from sick pigeons were inoculated into SPF embryonated chicken eggs for viral isolation and investigation of morphologic and hemagglutinating properties of the isolate, called PSH050513. Furthermore, virulence studies in SPF chickens and experimental pigeons were performed. The spike (S) glycoprotein gene of PSH050513 was further sequenced and analyzed. RESULTS PSH050513 was isolated and identified from the experimentally infected pigeons by a routine method, which was in accordance with Koch's postulates. The complete S protein (1,167 amino acids) was compared with published S protein sequences of other avian and mammalian coronaviruses. A high degree of sequence identity (79.3% to 99.6%) was observed between the S protein sequence of PSH050513 and published sequences of avian infectious bronchitis virus (IBV); only limited identity (< 37.8%) was observed with turkey coronavirus and mammalian coronaviruses. Furthermore, when the virus was inoculated into SPF chickens, pancreatitis developed. CONCLUSIONS AND CLINICAL RELEVANCE PSH050513 has been tentatively identified as a novel member of group 3 coronaviruses that have close genetic relationships with IBV strains.


title: Effect of Beetroot Juice on Moderate-Intensity Exercise at a Constant Rating of Perceived Exertion.

text: Dietary nitrate supplementation has been shown to reduce oxygen consumption at a fixed work rate. We questioned whether a similar effect would be observed during variable work rate exercise at a specific rating of perceived exertion (RPE), as is commonly prescribed for aerobic training sessions. Using a double-blind, placebo controlled, crossover design, ten females (25 ± 3 years; VO2peak 37.1 ± 5.3 ml/kg/min) performed two 20-min cycle ergometer trials at a constant RPE of 13 (somewhat hard) 2.5 hours following ingestion of 140 ml of concentrated beetroot juice (12.9 mmol nitrate), or nitrate-depleted placebo. Performance was measured in terms of total VO2 (L) consumed and total mechanical work (kJ) accomplished across each trial. Following each experimental trial, subjects rode at 75W for an additional 5 min to determine the effect of beetroot juice on fixed work rate exercise. Coefficients of variation in total VO2 (L) and work performed (kJ) during the RPE 13 clamp trials were 8.2 and 9.5%, respectively. Consumption of beetroot juice did not affect total VO2 or work performed during RPE 13 exercise, but lowered resting systolic blood pressure by ~5 mmHg (P=0.041) and oxygen consumption at 75W by ~4% (P=0.048), relative to placebo. Since the effect of beetroot juice on oxygen consumption is small and may be masked by daily variability during self-regulated exercise, it is unlikely to have a notable effect on daily training.


Plaque assay of bovine coronavirus in BEK-1 cells.


title: Feline viruses in wildcats from Scotland.

text: Few data are available on the prevalence of feline viruses in European wildcats (Felis silvestris). Previous surveys have indicated that wildcats may be infected with the common viruses of domestic cats, apart from feline immunodeficiency virus (FIV). In the present study, 50 wildcats trapped throughout Scotland (UK) between August 1992 and January 1997 were tested for evidence of viral infection. All were negative for FIV by several serological or virological methods. By contrast, 10% of the cats were positive for feline leukemia virus (FeLV) antigen and infectious virus was isolated from 13% of a smaller subset. Of the wildcats tested for respiratory viruses, 25% yielded feline calicivirus (FCV) and although no feline herpesvirus was isolated, 16% of the samples had neutralizing antibodies to this virus. Antibodies to feline coronavirus (FCoV) were found in 6% of samples. Feline foamy virus (FFV) was an incidental finding in 33% of samples tested. This study confirms that wildcats in Scotland are commonly infected with the major viruses of the domestic cat, except for FIV.


title: Treatment of the common cold with unrefined echinacea. A randomized, double-blind, placebo-controlled trial.

text: BACKGROUND Echinacea preparations are widely used to treat the common cold. OBJECTIVE To assess the efficacy of dried, encapsulated, whole-plant echinacea as early treatment for the common cold. DESIGN Randomized, double-blind, placebo-controlled community-based trial. SETTING University of Wisconsin-Madison, Madison, Wisconsin. PARTICIPANTS 148 registered students with common colds of recent onset. INTERVENTION An encapsulated mixture of unrefined Echinacea purpurea herb (25%) and root (25%) and E. angustifolia root (50%) taken in 1-g doses six times on the first day of illness and three times on each subsequent day of illness for a maximum of 10 days. MEASUREMENTS Severity and duration of self-reported symptoms of upper respiratory tract infection. RESULTS No statistically significant differences were detected between the echinacea and placebo groups for any of the measured outcomes. Trajectories of severity over time were nearly identical in the two groups. Mean cold duration was 6.01 days in both groups as a whole, 5.75 days in the placebo group, and 6.27 days in the echinacea group (between-group difference, -0.52 day [95% CI, -1.09 to 0.22 days]). After controlling for severity and duration of symptoms before study entry, sex, date of enrollment, and use of nonprotocol medications, researchers found no statistically significant treatment effect (adjusted hazard ratio, 1.24 [CI, 0.86 to 1.78]). Multivariable regression models assessing severity scores over time failed to detect statistically significant differences between the echinacea and placebo groups. CONCLUSION Compared with placebo, unrefined echinacea provided no detectable benefit or harm in these college students who had the common cold.


title: Scanning electron microscopy of abomasium and intestine of gnotoxenic calves infected either with rotavirus, coronarivus or enteropathogenic Escherichia coli or with rotavirus and E. coli.

text: Neonatal calf diarrhoea induced with several agents of infection was studied by scanning electron microscopy. In a gnotoxenic calf infected with E. coli K99+ Ent+, slight lesions of the small intestine were observed and desquamation or puffiness of microvilli occurred. In rotavirus-infected calves, the abomasum was covered with abudant mucous film and appeared to be desquamated. In the small intestine, no desquamation of epithelium was observed. Inoculation of the rotavirus and E. coli induced severe diarrhoea. The whole digestive tract, even the abomasum and colon, was eroded. Coronavirus induced marked lesions in all levels of the intestine. These results demonstrate unequivocally the pathogenic properties of the three infectious agnets, the synergistic effect of E. coli and rotavirus. Furthermore, the importance of the abomasum in neonatal diarrhoea is emphasized.


title: The Gastroenterological Society of Australia.

text: In this review, a summary of the objectives and activities of The Gastroenterological Society of Australia is given. It illustrates the multidisciplinary and multi-functional roles of a society that is confident and active in supporting and reflecting the views of its members in the pursuit of excellence in clinical practice, research and education in the various areas of digestive health.


title: Vaccinia virus entry, exit, and interaction with differentiated human airway epithelia.

text: Variola virus, the causative agent of smallpox, enters and exits the host via the respiratory route. To better understand the pathogenesis of poxvirus infection and its interaction with respiratory epithelia, we used vaccinia virus and examined its interaction with primary cultures of well-differentiated human airway epithelia. We found that vaccinia virus preferentially infected the epithelia through the basolateral membrane and released viral progeny across the apical membrane. Despite infection and virus production, epithelia retained tight junctions, transepithelial electrical conductance, and a steep transepithelial concentration gradient of virus, indicating integrity of the epithelial barrier. In fact, during the first four days of infection, epithelial height and cell number increased. These morphological changes and maintenance of epithelial integrity required vaccinia virus growth factor, which was released basolaterally, where it activated epidermal growth factor 1 receptors. These data suggest a complex interaction between the virus and differentiated airway epithelia; the virus preferentially enters the cells basolaterally, exits apically, and maintains epithelial integrity by stimulating growth factor receptors.


title: Reovirus binding to cell surface sialic acid potentiates virus-induced apoptosis.

text: Reovirus induces apoptosis in cultured cells and in vivo. Genetic studies indicate that the efficiency with which reovirus strains induce apoptosis is determined by the viral S1 gene, which encodes attachment protein sigma1. However, the biochemical properties of sigma1 that influence apoptosis induction are unknown. To determine whether the capacity of sigma1 to bind cell surface sialic acid determines the magnitude of the apoptotic response, we used isogenic reovirus mutants that differ in the capacity to engage sialic acid. We found that T3SA+, a virus capable of binding sialic acid, induces high levels of apoptosis in both HeLa cells and L cells. In contrast, non-sialic-acid-binding strain T3SA- induces little or no apoptosis in these cell types. Differences in the capacity of T3SA- and T3SA+ to induce apoptosis are not due to differences in viral protein synthesis or production of viral progeny. Removal of cell surface sialic acid with neuraminidase abolishes the capacity of T3SA+ to induce apoptosis. Similarly, incubation of T3SA+ with sialyllactose, a trisaccharide comprised of lactose and sialic acid, blocks apoptosis. These findings demonstrate that reovirus binding to cell surface sialic acid is a critical requirement for the efficient induction of apoptosis and suggest that virus receptor utilization plays an important role in regulating cell death.


title: Clinical characteristics of fatal patients with severe acute respiratory syndrome in a medical center in Taipei.

text: BACKGROUND The clinical spectrum of severe acute respiratory syndrome (SARS) varies widely in the way that asymptomatic carriers are believed to exist in the community. Still there are severe forms of illness in which the patients deteriorate unexpectedly within hours. This study delineates clinical characteristics of such fatal cases of SARS for the purpose of identifying patients with poor outcome. METHOD Patients with the diagnosis of probable or suspected SARS admitted to the Taipei Veterans General Hospital during the period from March 26, 2003 to May 25, 2003 were included. The medical records of fatal cases were retrospectively reviewed. RESULTS During the study period, thirty-six probable cases and 17 suspected cases of SARS were identified. Eight probable but none of the suspected cases died from acute respiratory distress syndrome (ARDS) with multiple organ dysfunction after a median of 6-day hospital stay (range, 1-30 days). All but 2 patients acquired the infection nosocomially. Of the fatal cases, four were males and 4 females, with the median age of 65 years (range, 29-76 yrs). All except 3 had co-morbid conditions, such as hypertension, diabetes mellitus, coronary artery disease or chronic obstructive pulmonary disease. The lactate dehydrogenase (LDH) values were abnormal (> 200 U/L) in all patients. The chest radiograph of these fatal cases consistently showed multifocal infiltration over the unilateral or bilateral lobe of the lung. CONCLUSIONS Patients of SARS who had advanced age, co-morbid conditions, highly elevated LDH and multifocal infiltration over chest radiograph should be closely monitored and actively treated.


Implications of the SARS outbreak for Canadian emergency departments.


title: Viral respiratory infections due to rhinoviruses: current knowledge, new developments.

text: Viral respiratory infections (VRIs) are among the most common reasons for which primary care providers are consulted. VRIs due to rhinoviruses-the most commonly implicated etiologic agent-constitute a syndrome characterized by signs and symptoms of a cold. Rhinoviruses have been implicated in respiratory tract illnesses such as sinusitis and otitis media, as well as lower respiratory complications in high-risk populations. Most patients treat VRI with over-the-counter remedies that have been demonstrated to produce marginal clinical benefits. The development of novel antiviral agents has intensified interest in VRIs. Pleconaril, a capsid-function inhibitor currently under FDA review, has been shown in clinical trials to reduce the duration and severity of rhinovirus VRIs. By targeting the cause of illness, antiviral agents represent an opportunity to reduce the substantial clinical burden of VRI. Furthermore, effective therapies can potentially reduce inappropriate antibiotic use for viral infections.


title: [An outbreak of SARS in Dongcheng District, Beijing during March to June 2003].

text: OBJECTIVE To describe epidemiological characteristics of an outbreak of severe acute respiratory syndrome (SRAS) in Dongcheng District, Beijing during March to June 2003. METHODS Data of SARS cases notified from Dongcheng District Center for Disease Control and Prevention (CDC) and supplemented by other channels were collected. All data were input into dataset files by Microsoft Excel-2000 software and analyzed with SPSS version 10.0 software. RESULTS Totally, 572 cases notified were collected during this period in Dongcheng District, Beijing, and 99 of them were excluded from SARS, because of diagnosis of common cold, pneumonia, measles, or rubella, etc. Actually, 473 SARS cases were analyzed. Attack rate of SARS in permanent residents of Dongcheng was 28.3 per 100,000. Forty-one of them died, with a case-fatality ratio of 8.7%. Outbreak of SARS in Dongcheng District started on March 14, with a peak during mid- and late April, and dropped from May 5, 2003. Persons were all susceptible to SARS, with the highest proportion at ages of 20-50 years, which accounted for 68.7% of the total cases. Average age of the patients at their onset was 40.7 years. No gender difference in SARS cases was found. Number of SARS cases in health care workers (HCWs) accounted for 18.0% and that in the retired persons accounted for 15.4% of the total cases. Cases occurred in all 10 sub-districts of Dongcheng. Totally, 230 of the 572 notified cases (40.2%) hospitalized at local hospitals under the jurisdiction of Dongcheng District. Eighteen of 85 cases of SARS occurred in health care workers of local hospitals, accounting for 4.5% of the total number of health care workers working at the wards caring for SARS patients or at fever clinics. There were 34.7% of SARS cases without any contact histories before their onset. Familial aggregation phenomena were observed in 41.8% of the cases and 18.1% of households. And, 7.4% (attack rate) in those exposed to SARS cases suffered the illness during the periods of quarantine. CONCLUSIONS SARS appeared outbreak in Dongcheng District, Beijing during March to June 2003. People were all susceptible to SARS, which mainly threatened the young adults and the middle-aged, as well as health care workers and the retired workers. Main mode of transmission was exposure to SARS patients in a near distance at hospitals or families. Prevention and control of SARS should be focused on early isolation of patients and quarantine for the contacts. Current available measures to prevent and control SARS proved effective.


title: Severe acute respiratory syndrome: radiographic review of 40 probable cases in Toronto, Canada.

text: PURPOSE To review radiographic findings of patients with probable severe acute respiratory syndrome (SARS) who were seen at a University of Toronto (Ontario, Canada) teaching hospital. MATERIALS AND METHODS Findings were reviewed for 40 patients who fulfilled the World Health Organization criteria for probable SARS. A template was designed for the analysis of each serial radiograph to observe patterns and distribution of disease, interval changes, and complications. The majority of radiographs were anteroposterior views. A clinical database of these patients was also collected for clinical-radiologic comparison. RESULTS The mean age of the patients (18 male, 22 female) was 42.7 years. Patients had a normal chest radiograph and focal, multifocal, and/or bilateral consolidation. The pattern of consolidation tended to be peripheral and poorly marginated and involved middle and lower lung zones. The serial sequence fell into two major subgroups, which correlated closely with clinical outcome. Consolidation in one group cleared within a matter of days, while the second group went on to develop rapid and extensive bilateral pneumonia, with a prolonged hospital stay. Subsegmental atelectasis and pleural complications were rarely observed. CONCLUSION SARS pneumonia can manifest as focal peripheral consolidation that clears relatively quickly and does not cause secondary complications or that progresses to bilateral consolidation and a more protracted clinical course.


title: Preclinical evaluation of antimicrobial efficacy and biocompatibility of a novel bacterial barrier dressing.

text: UNLABELLED  Wounds that become infected can lead to devastating consequences for patients, resulting in substantially increased healthcare costs. Bacterial barrier dressings are a first line of protection against developing wound infections. Most bacterial barrier dressings contain microbicidal chemicals (eg, silver ions, iodine, chlorhexidine) that are released from the dressings, which can be toxic to wound cells. A need exists for cost effective bacterial barrier dressings that absorb wound exudate and do not release toxic materials into the wound or increase the risk for developing bacterial resistance to the microbicidal chemical. The present study reports the development and properties of a novel bacterial barrier dressing that meets these needs. METHODS A high molecular weight (~250 k Daltons) polymer containing a high density of quaternary amines (polydiallyldimethylammonium chloride [polyDADMAC]) was permanently bonded onto cellulose fibers (gauze). Microbicidal and mammalian cell cytotoxicity tests were conducted using standard methods. Development of bacterial resistance to the microbicidal fibers was assessed over 10 passages. RESULTS The polyquat-treated bacterial barrier gauze dressing (BIOGUARD [BBD]) had high microbicidal activity even in the presence of proteinaceous fluid against a wide range of Gram-positive and Gram-negative bacteria. The BBD dressing passed all mammalian cell toxicity tests due to the non-leaching of the bactericidal polymer. Furthermore, the BBD dressing did not demonstrate any ability to induce bacterial resistance in selection vector testing. CONCLUSION This novel dressing featuring a bound microbicide offers another choice for wound caregivers to provide patients with an antimicrobial barrier dressing safe enough for prophylactic use to protect against wound infections.


title: COPD and cognitive impairment: the role of hypoxemia and oxygen therapy.

text: BACKGROUND several studies have shown an association between chronic obstructive pulmonary disease (COPD) and cognitive impairment. These studies have been limited by methodological issues such as diagnostic uncertainty, cross-sectional design, small sample size, or lack of appropriate referent group. This study aimed to elucidate the association between COPD and the risk of cognitive impairment compared to referent subjects without COPD. In patients with established COPD, we evaluated the impact of disease severity and impairment of respiratory physiology on cognitive impairment and the potential mitigating role of oxygen therapy. METHODS we used the Function, Living, Outcomes and Work (FLOW) cohort study of adults with COPD (n = 1202) and referent subjects matched by age, sex, and race (n = 302) to study the potential risk factors for cognitive impairment among subjects with COPD. Cognitive impairment was defined as a Mini-Mental State Exam score of <24 points. Disease severity was using Forced Expiratory Volume in one second (FEV(1)); the validated COPD Severity Score; and the BMI (Body Mass Index), Obstruction, Dyspnea, Exercise Capacity (BODE) Index. Multivariable analysis was used to control for confounding by age, sex, race, educational attainment, and cigarette smoking. RESULTS COPD was associated with a substantive risk of cognitive impairment compared to referent subjects (odds ratio [OR] 2.42; 95% confidence interval [CI] 1.043-6.64). Among COPD patients, none of the COPD severity measures were associated with the risk of cognitive impairment (P > 0.20 in all cases). Low baseline oxygen saturation was related to increased risk of cognitive impairment (OR for oxygen saturation ≤88% (OR 5.45; 95% CI 1.014-29.2; P = 0.048). Conversely, regular use of supplemental oxygen therapy decreased the risk for cognitive impairment (OR 0.14; 95% CI 0.07-0.27; P < 0.0001). CONCLUSION COPD is a major risk factor for cognitive impairment. Among patients with COPD, hypoxemia is a major contributor and regular use of home oxygen is protective. Health care providers should consider screening their COPD patients for cognitive impairment.