title: Kissing interaction between 3' noncoding and coding sequences is essential for porcine arterivirus RNA replication.

text: We used an infectious cDNA clone of porcine reproductive and respiratory syndrome virus (PRRSV) to investigate the presence of essential replication elements in the region of the genome encoding the structural proteins. Deletion analysis showed that a stretch of 34 nucleotides (14653 to 14686) within ORF7, which encodes the nucleocapsid protein, is essential for RNA replication. Strand-specific reverse transcription-PCR analysis of viral RNA isolated from transfected BHK-21 cells revealed that this region is required for negative-strand genomic RNA synthesis. The 34-nucleotide stretch is highly conserved among PRRSV isolates and folds into a putative hairpin. A 7-base sequence within the loop of this structure was suggested to base-pair with a sequence present in the loop of a hairpin located in the 3' noncoding region, resulting in a kissing interaction. Mutational analyses confirmed that this kissing interaction is required for RNA replication.


title: Evaluation of rapid antigen detection kits for diagnosis of equine rotavirus infection.

text: We evaluated antigen detection kits for human rotavirus with regard to their usefulness for diagnosing equine rotavirus infection. Limiting dilution analyses showed that of the seven kits investigated the Dipstick `Eiken' Rota (Dipstick) had the highest sensitivity to two serotypes of equine rotavirus. The Dipstick did not cross-react with several equine intestinal pathogens. An investigation using 249 fecal samples indicated that the sensitivity of the Dipstick was 81.9% and 47.3%, and its specificity was 98.2% and 99.0%, and its concordance rate was 92.8% and 68.3%, compared with values obtained using reverse transcription polymerase chain reaction and reverse transcription loop-mediated isothermal amplification, respectively. Although a negative result does not preclude the possibility of equine rotavirus infection, the Dipstick would be useful as routine test for diagnosing equine rotavirus infection in daily clinical practice because of its ease of handling.


title: Replicase genes of murine coronavirus strains A59 and JHM are interchangeable: differences in pathogenesis map to the 3' one-third of the genome.

text: The important roles of the spike protein and other structural proteins in murine coronavirus (MHV) pathogenesis have been demonstrated; however, the role of the replicase gene remains unexplored. We assessed the influence of the replicase genes of the highly neurovirulent MHV-JHM strain and the hepatotropic and mildly neurovirulent A59 strain in acute infection of the mouse. Analysis of chimeric A59/JHM recombinant viruses indicates that the replicase genes are interchangeable and that it is the 3' end of the genome, encoding the structural proteins, rather than the replicase gene, that determines the pathogenic properties of these chimeras.


docid: slerdvrh

title: Hybrid arch debranching and endograft repair in a patient with a ruptured thoracic aortic aneurysm.

text: Recent advances in hybrid techniques of aortic arch debranching allow for the repair of thoracic aortic arch aneurysm without requiring cardiopulmonary bypass or hypothermic circulatory arrest. We describe the repair of a ruptured proximal descending thoracic aortic aneurysm, using off-pump aortic arch debranching and antegrade transaortic deployment of a thoracic endograft in an elderly patient.


Organization of the IBV genome.


title: Structure-based design of enzyme inhibitors and receptor ligands.

text: With the ongoing progress in protein crystallography and NMR, structure-based drug design is adopting increasing importance in the search for new drugs. Modeling starts from the 3D structure of a target protein in order to construct molecules which are complementary to a binding site, in their geometry as well as in the pattern of their physicochemical properties around the molecules. The rational design process is accompanied by 3D structure determinations of different ligand-protein complexes. Most often, significantly improved binding affinities of the ligands are observed after several cycles of 3D structure determinations, the design of compounds with appropriate structural modifications, synthesis, and testing of the new drug candidates. As an alternative, pharmacophore models are derived from the 3D structures of active analogs. A risk with lead structure optimization by structure-based design is the neglect of other important biological properties, such as bioavailability and metabolic stability. Recent applications of structure-based design, as well as success stories in the search for new, potent and selective HIV protease inhibitors, thrombin inhibitors, neuraminidase inhibitors and integrin receptor antagonists, are reviewed.


docid: aacjqsmp

title: Which bio-weapons might be used by terrorists against the United Kingdom?

text: The properties of potential biological weapon agents for bioterrorism include a consistent effect at low dosage and short incubation period in a population of low immunity, being difficult to treat, able to be produced in bulk, stable in storage and readily disseminated. Possible agents include smallpox, haemorrhagic fever viruses, anthrax, tularaemia and plague. The example of Severe Acute Respiratory Syndrome (SARS) demonstrates the possible consequences of an act of bioterrorism, but also the necessary global response. There is scepticism about the practicability of surveillance schemes and the global elimination of biological weapons though the Biological and Toxin Weapons Convention remains urgent.


title: [An interpretation on perinatal and neonatal management plan for prevention and control of SARS-CoV-2 infection (2nd Edition)].

text: The epidemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues so far. The cases of SARS-CoV-2 infection have been reported in pregnant women and neonates as special groups. Perinatal and neonatal management plan for prevention and control of SARS-CoV-2 infection (2nd Edition) has been worked out by the Editorial Committee of Chinese Journal of Contemporary Pediatrics. This paper presents an interpretation on the 2nd Edition of the management plan, so as to facilitate readers to better understand it.


title: CD147 inhibits the nuclear factor of activated T-cells by impairing Vav1 and Rac1 downstream signaling.

text: CD147 is a transmembrane protein that plays crucial roles in the development and function of the reproductive, visual, and nervous systems. CD147 also exerts positive and negative actions in T-cells by still obscure mechanisms. In this study, we have analyzed the expression, localization, and function of CD147 during T-cell receptor signaling responses. We show here that CD147 is an integral component of the T-cell immune synapse and that its overexpression leads to the inhibition of NF-AT (nuclear factor of activated T-cells) activity induced by Vav1, a Rac1 exchange factor. This inhibitory activity is mediated by the CD147 intracellular tail and is totally independent of its extracellular or transmembrane regions. The molecular dissection of the influence of CD147 on the Vav1 pathway indicates that its inhibitory action takes place downstream of Vav1 and Rac1 but upstream of the serine/threonine kinases JNK and Pak1. The interference of CD147 with these pathways is highly specific because the overexpression of CD147 does not affect the activity of other GDP/GTP exchange factors or the stimulation of the ERK cascade. Finally, we show that the CD147 knockdown in Jurkat cells promotes higher levels of NF-AT stimulation and Pak1 phosphorylation upon T-cell receptor cross-linking. Instead, the lack of CD147 does not affect other signaling cascades that participate in the same cellular response. Taken together, these results indicate that CD147, via the selective inhibition of specific downstream elements of the Vav1/Rac1 route, contributes to the negative regulation of T-cell responses.


title: Community acquired pneumonia in the tropics.

text: PURPOSE OF REVIEW Due to the exponential growth of international exchange, millions of travelers are exposed to respiratory pathogens in the tropics and may return ill. Community-acquired pneumonia is one of the more prevalent infections. RECENT FINDINGS The acquisition of infections in the tropics, including community-acquired pneumonias, has been described for several centuries. During recent decades some microorganisms have been disclosed as causative of the disease (Legionella pneumophila in 1976 and hantavirus in 1990); other microorganisms are real new pathogens that were not previously demonstrated to have a pathogenic role in humans (e.g. severe acute respiratory syndrome coronavirus producing an outbreak in 2003 and H5N1 avian influenza virus producing an increasing number of human cases over the last few years). SUMMARY A number of microorganisms may produce pneumonia in people who live or have traveled to tropical zones. History, including geography and epidemiology, physical exam and complementary workout are precious tools for the diagnosis, therapy and prevention. Exposure to microorganisms in tropical areas may show different patterns. A high index of suspicion, detailed investigation of travel, exposure history of the patient, and a basic understanding of the incubation periods and distribution of the various potential pathogens are imperative for the diagnosis.


title: All but the shortest polymorphic forms of the viral receptor DC-SIGNR assemble into stable homo- and heterotetramers.

text: Polymorphisms that affect the length of the extracellular neck region of the endothelial receptor DC-SIGNR (dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin-related protein) have been linked to differences in susceptibility to infection by enveloped viruses. We have characterized the effects of these polymorphisms on the ability of DC-SIGNR to form tetramers containing the clusters of sugar-binding sites needed for binding to viral envelope glycoproteins. Chemical cross-linking and analytical ultracentrifugation experiments have been used to show that only the smallest form of DC-SIGNR is defective in homotetramer assembly. A novel affinity-tagging approach has been employed to demonstrate that, contrary to previous speculation, heterotetramers can be assembled efficiently from DC-SIGNR polypeptides of different lengths. The heterotetramers are stable and can be detected in fibroblasts transfected with multiple forms of DC-SIGNR. These results provide a molecular basis for interpreting the way polymorphisms affect interactions with viruses.


title: Monopolar active accessories can be connected to Covidien ForceTriad electrosurgical generators incorrectly, disabling coagulation mode.

text: The monopolar output receptacle on the Covidien ForceTriad electrosurgical generator is designed in such a way that users can unknowingly connect active accessories in the wrong orientation, disabling the system's coagulation function. The manufacturer is developing labeling for ForceTriad production units that depicts the proper orientation in which to connect the accessory during setup. Covidien is currently considering how it will address units already in the field.


title: Novel coronavirus associated with severe respiratory disease: case definition and public health measures.

text: Two cases of rapidly progressive acute respiratory infection in adults associated with a novel coronavirus have generated an international public health response. The two infections were acquired three months apart, probably in Saudi Arabia and Qatar. An interim case definition has been elaborated and was published on the World Health Organization website on 25 September 2012.


Reframing HIV and AIDS.


title: [Variability analysis of S2 gene of SARS-CoV].

text: OBJECTIVE To determine the sequence of S2 gene of SARS-associated coronavirus (SARS-CoV) GD322 and analyze the phyletic evolution of S2 gene. METHOD S2 gene fragment was amplified from SARS-CoV GD322 genome with RT-PCR and ligated to pGEM-T vector for sequence analysis after transformation of the plasmid into E. coli DH5a. The variability of S2 genes and S2 proteins from 12 strains isolated in the early, intermediate and advanced stages of the SARS outbreak were analyzed and the phylogenetic tree was constructed with Lasergene, Clustal X, DNAman and Treeview. T cell antigen epitopes of S2 protein were predicted on the basis of Internet database. RESULT With the epidemic spread of SARS-CoV, the S2 genes of the virus tended to become stable. Homology of S2 genes of SARS-CoV isolated in advanced stage of the outbreak reached 99.9%. Prediction of T cell antigen epitope showed that mutation at the 57th amino acid effected T cell antigen epitope. CONCLUSION S2 gene of GD322 SARS-CoV is relatively stable during the epidemic spread of the virus, and mutation at the 57th amino acids of S2 protein may affect the T cell antigen epitope.


title: Malaria surveillance--United States, 2001.

text: PROBLEM/CONDITION Malaria is caused by any of four species of intraerythrocytic protozoa of the genus Plasmodium (i.e., P. falciparum, P. vivax, P. ovale, or P. malariae). These parasites are transmitted by the bite of an infective female Anopheles sp. mosquito. The majority of malaria infections in the United States occur among persons who have traveled to areas with ongoing transmission. In the United States, cases can occur through exposure to infected blood products, by congenital transmission, or by local mosquitoborne transmission. Malaria surveillance is conducted to identify episodes of local transmission and to guide prevention recommendations for travelers. PERIOD COVERED This report covers cases with onset of illness in 2001. DESCRIPTION OF SYSTEM Malaria cases confirmed by blood film are reported to local and state health departments by health-care providers or laboratory staff. Case investigations are conducted by local and state health departments, and reports are transmitted to CDC through the National Malaria Surveillance System (NMSS). Data from NMSS serve as the basis for this report. RESULTS CDC received reports of 1,383 cases of malaria with an onset of symptoms in 2001 among persons in the United States or one of its territories. This number represents a decrease of 1.4% from the 1,402 cases reported for 2000. P. falciparum, P. vivax, P. malariae, and P. ovale were identified in 50.1%, 27.8%, 4.5%, and 3.6% of cases, respectively. Fourteen patients (1.0% of total) were infected by >/=2 species. The infecting species was unreported or undetermined in 179 (12.9%) cases. Compared with 2000, the number of reported malaria cases acquired in Africa increased by 13.2% (n = 886), whereas the number of cases acquired in Asia (n = 163) and the Americas (n = 240) decreased by 31.5% and 11.4%, respectively. Of 891 U.S. civilians who acquired malaria abroad, 180 (20.2%) reported that they had followed a chemoprophylactic drug regimen recommended by CDC for the area to which they had traveled. Two patients became infected in the United States, one through congenital transmission and one whose infection cannot be linked epidemiologically to secondary cases. Eleven deaths were attributed to malaria, 10 caused by P. falciparum and one caused by P. ovale. INTERPRETATION The 1.4% decrease in malaria cases in 2001, compared with 2000, resulted primarily from a decrease in cases acquired in Asia and the Americas, but this decrease was offset by an increase in the number of cases acquired in Africa. This decrease probably represents year-to-year variation in malaria cases, but also could have resulted from local changes in disease transmission, decreased travel to malaria-endemic regions, fluctuation in reporting to state and local health departments, or an increased use of effective antimalarial chemoprophylaxis. In the majority of reported cases, U.S. civilians who acquired infection abroad were not on an appropriate chemoprophylaxis regimen for the country in which they acquired malaria. PUBLIC HEALTH ACTIONS Additional information was obtained concerning the 11 fatal cases and the two infections acquired in the United States. Persons traveling to a malarious area should take one of the recommended chemoprophylaxis regimens appropriate for the region of travel, and travelers should use personal protection measures to prevent mosquito bites. Any person who has been to a malarious area and who subsequently develops a fever or influenza-like symptoms should seek medical care immediately and report their travel history to the clinician; investigation should include a blood-film test for malaria. Malaria infections can be fatal if not diagnosed and treated promptly. Recommendations concerning malaria prevention can be obtained from CDC by calling the Malaria Hotline at 770-488-7788 or by accessing CDC's Internet site at http://www.cdc.gov/travel.


docid: jbmphgzh

title: Single-stage full-thickness scalp reconstruction using acellular dermal matrix and skin graft.

text: Full-thickness scalp defects with exposed calvarium pose a reconstructive challenge, particularly in patients with extensive comorbidities. A single-stage acellular dermal matrix and split-thickness skin graft reconstruction represents a simple and valuable surgical approach to achieving durable scalp coverage without requiring a donor-site or prolonged treatment. Reconstruction of full-thickness scalp defects with exposed calvarium is a difficult problem that generally requires local or free flap reconstruction. However, patients with significant medical comorbidities present a further challenge given the risks of a major surgical procedure. Simple skin graft directly onto bone frequently fails and does not provide durable coverage, while combined artificial skin substitute and split-thickness skin graft approach involves a prolonged treatment period with multiple-staged procedures. Herein, we present a case of an 82-year-old female patient with complex medical comorbidities with a large scalp defect and calvarial exposure following Moh's surgery. She was successfully treated with a single-stage acellular dermal matrix and a STSG reconstruction. Her treatment period was effectively shortened, and she had an excellent clinical outcome.


title: Acute exacerbation of chronic bronchitis: a primary care consensus guideline.

text: OBJECTIVE To develop consensus on appropriate treatment for acute exacerbation of chronic bronchitis (AECB). CHARACTERISTICS AND ETIOLOGY: Patients with chronic bronchitis have an irreversible reduction in maximal airflow velocity and a productive cough on most days of the month for 3 months over 2 consecutive years. An AECB is characterized by a period of unstable lung function with worsening airflow and other symptoms. Most (80%) cases of AECB are due to infection, with half due to aerobic bacteria. The remaining 20% are due to noninfectious causes such as environmental factors or medication nonadherence. MANAGEMENT Supportive care should be provided to all patients, which might include removal of irritants, use of a bronchodilator, oxygen, hydration, use of a systemic corticosteroid, and chest physical therapy. Antibacterial treatment should be reserved for patients with at least 1 key symptom (ie, increased dyspnea, sputum production, sputum purulence) and 1 risk factor (ie, age > or = 65 years, forced expiratory volume in 1 second < 50% of the predicted value, > or = 4 AECBs in 12 months, 1 or more comorbidities). A newer macrolide, extended-spectrum cephalosporin, or doxycycline is appropriate for an exacerbation of moderate severity, and high-dose amoxicillin/clavulanate or a respiratory fluoroquinolone should be used for a severe exacerbation. There has been increasing antibacterial resistance by the 3 most prevalent pathogens (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis). CONCLUSION Although all AECB patients should receive supportive care, only patients with at least 1 key symptom and 1 risk factor should receive antibiotic therapy.


docid: uonoabcu

title: Neospora caninum infection in birds: experimental infections in chicken and embryonated eggs.

text: Neospora caninum causes economical impact in cattle-raising farms since it is implicated as the major cause of bovine abortions. Although infection by the parasite has been widely described in mammals, the role of birds in its life-cycle is still obscure. Therefore, this work aimed to evaluate the infection by N. caninum in different chicken models. Experimental infections were conducted in 7-day-old chicks, laying hens and embryonated eggs, where samples were analysed for parasite burden, IgG antibodies and lesions promoted. Chickens demonstrated an asymptomatic infection, although with seroconversion and systemic replication of the parasite. In laying hens, no signs of vertical transmission were observed. However, embryonated eggs inoculated by the allantoic cavity route demonstrated susceptibility to infection, with mortality rates around 50% independent of the inoculum dose. Additionally, dogs became infected after ingestion of different amounts of inoculated eggs, producing either oocysts or specific IgG antibodies. The results herein presented demonstrate that chickens may be intermediate hosts of N. caninum and that embryonated eggs could be a useful model to study the parasite's biology.


title: Portable power supply options for positive airway pressure devices.

text: INTRODUCTION Patients with obstructive sleep apnea (OSA) often face the challenge of how to power their positive airway pressure (PAP) devices when alternating current power supplies are not available in remote areas with lack of electricity or frequent power outages. This article elucidates portable power supply options for PAP devices with the aim to increase alternative power source awareness among medical providers. METHODS A search of scientific databases (Medline, Scopus, Web of Science, Google Scholar, and the Cochrane Library) was carried out on the topic of alternative portable power supply options for treatment of OSA. RESULTS Scientific databases listed above yielded only limited results. Most articles were found via Google search. These articles were reviewed for alternative power supply options for OSA patients when alternating current is not available. The power supply options in this article include lead-acid batteries (starter, marine and deep-cycle batteries), lithium ion batteries, solar kits, battery packs, backup power systems, portable generators, and travel-size PAP devices. CONCLUSIONS There are several options to power PAP devices with direct current when alternating current is not available. Knowledgeable primary care physicians especially in rural and remote areas can help OSA patients improve PAP compliance in order to mitigate morbidity and long-term complications of OSA.


title: Severe acute respiratory syndrome and its lesions in digestive system.

text: Severe acute respiratory syndrome (SARS) is an infectious atypical pneumonia that has recently been recognized in the patients in 32 countries and regions. This brief review summarizes some of the initial etiologic findings, pathological description, and its lesions of digestive system caused by SARS virus. It is an attempt to draw gastroenterologists and hepatologists' attention to this fatal illness, especially when it manifests itself initially as digestive symptoms.


title: Midazolam plasma concentration after anesthesia premedication in clinical routine - an observational study : Midazolam plasma concentration after anesthesia premedication.

text: BACKGROUND Midazolam is commonly used as a pre-anesthesia anxiolytic. It`s elimination may not be fast enough for short procedures. In orally premedicated patients we obtained midazolam plasma concentrations at the end of surgical procedures and compared those to concentrations at anesthesia induction. METHODS The study was conducted prospectively with consent of the local ethics committee (Ethikkomission Kanton Thurgau, Switzerland) and carried out with written informed consent of each patient. Female patients aged 20 to 60 years undergoing elective procedures with general anesthesia were included, and were divided in two groups according to the planned surgical time: group S (<30 min) and group L (90-120 min), respectively. All patients received 7.5 mg Midazolam po as premedication. Blood samples were drawn at anesthesia induction, and at the end of surgery. Data were compared with t-test (independent samples; significance level p <0.05). RESULTS Twenty-five patients per group were included. Four patients were excluded from analysis, since midazolam was not detectable in any samples. Time of premedication to the 1st blood sample was not statistically different between groups, neither were Midazolam plasma levels at this time point (p = 0.94). None of the patients from group L (n = 24), but five patients in group S (n = 22) did have a higher plasma level of Midazolam at the end of the case compared to the beginning. CONCLUSIONS The elimination half-life of oral Midazolam can lead to higher plasma levels at the end of a short procedure compared to those at induction of anesthesia. TRIAL REGISTRATION German Clinical Trials Register (Deutsches Register Klinischer Studien), DRKS00005429 ; date of registration 3rd January 2014.


title: Hepatobiliary pathology.

text: PURPOSE OF REVIEW Liver biopsy continues to be an essential component in the evaluation of many widely prevalent liver diseases, including chronic hepatitis C, fatty liver, and liver tumors. This annual review of publications in hepatobiliary pathology highlights recent pathologic studies that can be applied to the daily practice of interpreting liver biopsy, explant, and postmortem specimens. RECENT FINDINGS The problem of the fatty liver was the subject of many studies. In chronic hepatitis C, genotype 3 infection results in moderate to marked fat that is ameliorated with successful antiviral therapy. In nonalcoholic steatohepatitis, in which the metabolic syndrome is often operative, gene microarray analysis showed altered expression of genes involved in insulin sensitivity and maintenance of mitochondrial function. Pathologic changes affecting centrilobular regions were described in the context of heart disease, Budd-Chiari syndrome, and the sinusoidal obstruction syndrome (venoocclusive disease). A mutation in ferroportin 1 produced a form of hemochromatosis with excessive iron in hepatocytes and also in Kupffer cells and macrophages. Immunostains for Hep Par 1 and polyclonal carcinoembryonic antigen remain important cornerstones in the immunohistochemical diagnosis of hepatocellular carcinoma and its distinction from metastatic adenocarcinoma and cholangiocarcinoma. SUMMARY This report reviews recent articles addressing hepatobiliary pathology. In the areas of viral and drug hepatitis, fatty liver, hemochromatosis, Wilson disease, several biliary tract disorders, and pathology of liver tumors, the emerging data have important diagnostic applications.


title: Involvement of a stem-loop structure in the location of junction sites in viral RNA recombination.

text: Recombination between RNAs associated with turnip crinkle virus is thought to occur during plus-strand synthesis at motifs resembling the 5'-ends of genomic, subgenomic and satellite RNAs. Common structural regions encompassing the motifs have been found for major crossover sites on two different minus-strand templates, with junctions preferentially located in a single-stranded region at the 3' base of a hairpin. Base changes, deletions and compensatory alteration constructed in and around the hairpin in the region of the turnip crinkle virus genomic RNA involved in recombination support the importance of the hairpin for normal crossover site selection. This region of the genomic RNA is also important for replication of the viral genomic RNA in plants and protoplasts, suggesting a common link between sequences required for recombination and viral replication.


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.