title: Accumulation of recombinant SARS-CoV spike protein in plant cytosol and chloroplasts indicate potential for development of plant-derived oral vaccines.

text: Plants are promising candidates as bioreactors for the production of oral recombinant proteins in the biopharmaceutical industry. As an initial step toward provision of an oral vaccine against the severe acute respiratory syndrome coronavirus (SARS-CoV), we have expressed a partial spike (S) protein of SARS-CoV in the cytosol of nuclear-transformed plants and in the chloroplasts of plastid-transformed plants. In the construction of both nuclear and plastid transformation vectors, a 2-kilobase nucleotide sequence encoding amino acids 1-658 of the SARS-CoV spike protein (S1) was modified with nucleotide changes, but not amino acid changes, to optimize codon usage for expression in plants. To investigate the subcellular localization of S1 during transient expression in tobacco leaves, a translational fusion consisting of S1 and the green fluorescent protein (GFP) was generated. Following agroinfiltration of tobacco leaves, analysis by laser confocal scanning microscopy revealed that the S1:GFP fusion protein was localized to the cytosol. In stable transgenic tobacco plants and lettuce plants generated by Agrobacterium-mediated transformation, tobacco and lettuce leaves were observed to express the S1 at high levels from the Cauliflower Mosaic Virus 35S promoter with Northern blot analysis. When the S1 was expressed in transplastomic tobacco, S1 messenger RNA and its corresponding protein were detected on Northern and Western blot analyses, respectively. Our results demonstrate the feasibility of producing S1 in nuclear- and chloroplast-transformed plants, indicating its potential in subsequent development of a plant-derived and safe oral recombinant subunit vaccine against the SARS-CoV in edible plants.


title: Heterogeneous influenza activity across Europe during the winter of 2002-2003.

text: Influenza activity varied across Europe during the 2002-2003 season both in terms of the intensity of clinical activity and the circulating virus types/subtypes. Influenza B was generally predominant in the 'western' parts of Europe (Portugal, Spain, the United Kingdom and Ireland) and influenza A (H3N2) in the 'central' and 'eastern' areas (Germany, Italy, Denmark, Switzerland, Poland, Slovenia, the Slovak Republic, the Netherlands). A number of countries experienced mixed seasons, first experiencing activity associated with influenza B and then with influenza A (Belgium, France and Spain). Generally, countries where influenza B was predominant had low (compared to historical data) levels of intensity (a mild season) and longer periods of influenza activity compared to countries where influenza A (H3N2) was predominant. A number of countries, all where influenza A (H3N2) was predominant, reported high levels of intensity compared to historical data: the Czech Republic, Denmark, Germany and Poland. In the six countries where age-specific incidence rates were available, the highest rates were observed among those aged 0-14 years. The influenza virus strains circulating in Europe had a good match with the virus strains in the influenza vaccine. A small number of isolates (A/Fujian/411/2002 (H3N2)-like) were reported at the end of the season that had a reduced reactivity to anti-sera of the vaccine strain. The composition of the 2003-2004 influenza vaccine is the same as during the 2002-2003 season.


title: Double-stranded RNA stimulates the expression of monocyte chemoattractant protein-1 in BEAS-2B bronchial epithelial cells.

text: BEAS-2B bronchial epithelial cells were treated with polyinosinic-polycytidylic acid (poly IC), a synthetic double-stranded RNA (dsRNA) analog, and the expressions of monocyte chemoattractant protein-1 (MCP-1) mRNA and protein were analyzed by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay. Poly IC enhanced the expression of MCP-1 and release of mononuclear cell chemotactic activity, which were inhibited by dexamethasone pre-treatment. The poly IC-induced up-regulation of MCP-1 was blocked by 2-aminopurine, a specific inhibitor of dsRNA-dependent protein kinase, but not by nuclear factor (NF)-kappaB inhibitor SN50.


title: Development and application of a Saccharomyces cerevisiae-expressed nucleocapsid protein-based enzyme-linked immunosorbent assay for detection of antibodies against infectious bronchitis virus.

text: A Saccharomyces cerevisiae-expressed nucleocapsid (N) polypeptide of the M41 strain of infectious bronchitis virus (IBV) was used as antigen in a recombinant yeast-expressed N protein-based enzyme-linked immunosorbent assay (Y-N-ELISA). The Y-N-ELISA was rapid, sensitive, and specific for detecting chicken serum antibodies to IBV, and it compared favorably with a commercial ELISA.


title: Comparison of Cryptosporidium parvum viability and infectivity assays following ozone treatment of oocysts.

text: Several in vitro surrogates have been developed as convenient, user-friendly alternatives to mouse infectivity assays for determining the viability of Cryptosporidium parvum oocysts. Such viability assays have been used increasingly to determine oocyst inactivation following treatment with chemical, physical, or environmental stresses. Defining the relationship between in vitro viability assays and oocyst infectivity in susceptible hosts is critical for determining the significance of existing oocyst inactivation data for these in vitro assays and their suitability in future studies. In this study, four viability assays were compared with mouse infectivity assays, using neonatal CD-1 mice. Studies were conducted in the United States and United Kingdom using fresh (<1 month) or environmentally aged (3 months at 4 degrees C) oocysts, which were partially inactivated by ozonation before viability and/or infectivity analyses. High levels of variability were noted within and between the viability and infectivity assays in the U.S. and United Kingdom studies despite rigorous control over oocyst conditions and disinfection experiments. Based on the viability analysis of oocyst subsamples from each ozonation experiment, SYTO-59 assays demonstrated minimal change in oocyst viability, whereas 4',6'-diamidino-2-phenylindole-propidium iodide assays, in vitro excystation, and SYTO-9 assays showed a marginal reduction in oocyst viability. In contrast, the neonatal mouse infectivity assay demonstrated significantly higher levels of oocyst inactivation in the U.S. and United Kingdom experiments. These comparisons illustrate that four in vitro viability assays cannot be used to reliably predict oocyst inactivation following treatment with low levels of ozone. Neonatal mouse infectivity assays should continue to be regarded as a "gold standard" until suitable alternative viability surrogates are identified for disinfection studies.


title: Management protocols for animals in captive propagation and reintroduction programmes.

text: Species Survival Plans in North America--and comparable programmes in other parts of the world--address the management issues related to maintaining populations of endangered species in captivity. The need has been recognized for universal methods of assessing, evaluating, monitoring and preventing the transmission of disease to naive wildlife by reintroduced species. Standardized protocols are presented for evaluation of the health status of captive animals intended for release.


title: [Viruses and bats: rabies and Lyssavirus].

text: Recent emerging zoonoses (hemorrhagic fevers due to Ebola or Marburg virus, encephalitis due to Nipah virus, severe acute respiratory syndrome due to SRAS virus...) outline the potential of bats as vectors for transmission of infectious disease to humans. Such a potential is already known for rabies encephalitis since seven out of the eight genotypes of Lyssavirus are transmitted by bats. In addition, phylogenetic reconstructions indicate that Lyssavirus have evolved in chiropters before their emergence in carnivores. Nevertheless, carnivores remain the most critical vectors for public health, in particular dogs that are originating 55.000 rabies deaths per year, essentially in developing countries. Rabies control in carnivores by parenteral (dog) or oral (wild carnivores) vaccination is efficacious and campaigns start to be more widely applied. On the other hand, rabies control in bat still remains non realistic, particularly as the pathogenicity of bat Lyssavirus for bats is still under debate, suggesting that a "diplomatic relationship" between partners would have arisen from a long term cohabitation. While comparing the interactions that humans and bats establish with Lyssavirus, scientists try to understand the molecular basis ofpathogenicity in man, a indispensable prerequisite to identify antiviral targets in a perspective of therapy.


title: The role of type I interferon production by dendritic cells in host defense.

text: Type I interferons (IFN) and dendritic cells (DC) share an overlapping history, with rapidly accumulating evidence for vital roles for both production of type 1 IFN by DC and the interaction of this IFN both with DC and components of the innate and adaptive immune responses. Within the innate immune response, the plasmacytoid DC (pDC) are the "professional" IFN producing cells, expressing specialized toll-like receptors (TLR7 and -9) and high constitutive expression of IRF-7 that allow them to respond to viruses with rapid and extremely robust IFN production; following activation and production of IFN, the pDC subsequently mature into antigen presenting cells that help to shape the adaptive immune response. However, like most cells in the body, the myeloid or conventional DC (mDC or cDC) also produce type I IFNs, albeit typically at a lower level than that observed with pDC, and this IFN is also important in innate and adaptive immunity induced by these classic antigen presenting cells. These two major DC subsets and their IFN products interact both with each other as well as with NK cells, monocytes, T helper cells, T cytotoxic cells, T regulatory cells and B cells to orchestrate the early immune response. This review discusses some of the converging history of DC and IFN as well as mechanisms for IFN induction in DC and the effects of this IFN on the developing immune response.


title: Diagnostic investigation of bovine viral diarrhea infection in a Minnesota dairy herd.

text: Bovine viral diarrhea (BVD) virus infection was diagnosed in neonatal calves with enteritis. Successful diagnostic procedures included direct immunofluorescence of frozen tissue sections, histopathology, and virus isolation. Virus isolation from buffy coats and serum was successful in detecting infected animals, whereas direct immunofluorescence of buffy coat samples was found to be less reliable. Virus was not isolated from any fecal samples. Booster vaccinations and the culling of animals shedding virus resulted in improved calf viability in this herd. It is suggested that procedures for the diagnosis of BVD virus infection should always be included in the diagnosis of neonatal calf enteritis.


Do respirators protect health-care workers from airborne infectious diseases?


A question of age.


title: Pandemic influenza and its implications for transplantation.

text: Influenza viruses are important infections in transplant recipients. They may lead to complications including viral pneumonia, secondary bacterial infections and graft dysfunction. There has been a recent widespread outbreak of highly pathogenic H5N1 avian influenza among domestic poultry and wild birds along with a number of human cases with severe disease and high mortality. Genetic changes in the H5N1 virus may lead to efficient human-to-human transmission, heralding the onset of the next influenza pandemic. Discussed are the implications that such a pandemic may have on transplant patients. Logical inferences can be made from data on influenza in transplant patients and from experience with other respiratory virus outbreaks. In the event of a pandemic, it is likely that transplant patients will have more severe disease and higher mortality as compared to the general population. Vaccination and antiviral strategies may be less effective in this population. Implications for transplant programs in general are also discussed.


title: Outbreak of adenovirus type 1 severe pneumonia in a French intensive care unit, September-October 2012.

text: We herein describe and analyse the first outbreak of severe pneumonia caused by human adenovirus type1 (HAdV C type 1), which included immunocompetent patients in an intensive care unit (ICU) of Marseille, France, and occurred between September and October 2012. Seven successive patients were diagnosed by HAdV specific real-time polymerase chain reaction with a positive bronchoalveolar lavage. After the collection of nasopharyngeal swabs from healthcare workers, three nurses working night shifts tested positive for HAdV C including one that had exhibited respiratory signs while working one week before the outbreak. She was the most likely source of the outbreak. Our findings suggest that HAdV-1 could be considered as a possible cause of severe pneumonia even in immunocompetent patients with a potential to cause outbreaks in ICUs. HAdV rapid identification and typing is needed to curtail the spread of this pathogen. Reinforcing hand hygiene with antiseptics with demonstrated activity against non-enveloped viruses and ensuring that HCWs with febrile respiratory symptoms avoid direct patient contact are critical measures to prevent transmission of HAdV in healthcare settings.


title: Prediction of consensus RNA secondary structures including pseudoknots.

text: Most functional RNA molecules have characteristic structures that are highly conserved in evolution. Many of them contain pseudoknots. Here, we present a method for computing the consensus structures including pseudoknots based on alignments of a few sequences. The algorithm combines thermodynamic and covariation information to assign scores to all possible base pairs, the base pairs are chosen with the help of the maximum weighted matching algorithm. We applied our algorithm to a number of different types of RNA known to contain pseudoknots. All pseudoknots were predicted correctly and more than 85 percent of the base pairs were identified.


title: Serologic survey for viral and bacterial infections in western populations of Canada lynx (Lynx canadensis).

text: A serologic survey for exposure to pathogens in Canada lynx (Lynx canadensis) in western North America was conducted. Samples from 215 lynx from six study areas were tested for antibodies to feline parvovirus (FPV), feline coronavirus, canine distemper virus, feline calicivirus, feline herpesvirus, Yersinia pestis, and Francisella tularensis. A subset of samples was tested for feline immunodeficiency virus; all were negative. For all other pathogens, evidence for exposure was found in at least one location. Serologic evidence for FPV was found in all six areas but was more common in southern populations. Also, more males than females showed evidence of exposure to FPV. Overall, prevalences were low and did not exceed 8% for any of the pathogens tested. This suggests that free-ranging lynx rarely encounter common feline pathogens.


New insights into the mechanisms of RNA recombination.


title: Equine arteritis virus subgenomic mRNA synthesis: analysis of leader-body junctions and replicative-form RNAs.

text: In addition to the genomic RNA, a 3' coterminal nested set of six subgenomic mRNAs is produced in equine arteritis virus (EAV)-infected cells. The seven viral RNAs are also 5' coterminal, since they all contain a 206-nucleotide common leader sequence which is identical to the 5' end of the genome. A conserved penta-nucleotide sequence motif, 5' UCAAC 3', was shown to be present at the junctions between the leader and body sequences in each of the mRNAs. In addition, two alternative junction sites were detected for mRNA 3. Seven replicative-form (RF) RNAs (RFs I to VII), corresponding to the genomic RNA and each of the subgenomic EAV mRNAs, could be prepared from lysates of infected cells. The minus-strand RNA contents of these RF RNAs were analyzed by using an RNase protection assay with an RNA probe containing the mRNA 2 leader-body junction. It was established that RF II contained a negative-stranded copy of mRNA 2, including a complementary leader sequence. The presence of subgenomic minus-strand RNA in RFs is indicative of a function as a transcription template during the production of EAV subgenomic mRNAs.


title: Plasma Concentration of Meloxicam in Pediatric Rats.

text: In this study, we compared the plasma concentrations of meloxicam in pediatric rat pups (ages: 7, 14, 21, and 28 d) with those of young adult rats. Adult rats received 1.34 mg/kg SC meloxicam to determine the target peak plasma concentration (Cmax) for comparison with the pediatric animals. Pediatric rats received 1.34 mg/kg SC meloxicam, and in all age groups, Cmax met or exceeded that in adults (11.5 ±2.7 μg/mL). Plasma concentrations were similar between male and female pups within age groups, and peak plasma concentration was achieved more rapidly in rat pups than adults. The analgesic efficacy of this dose was not evaluated in this study.


title: Allergens, viruses, and asthma exacerbations.

text: In adults and children with asthma, viral infections (rhinovirus [RV] infection being the most prevalent) will often trigger an increase in symptomatology. The mechanisms responsible for viral-induced exacerbations remain uncertain. Proposed mechanisms include direct infection of the lower respiratory tract, the inflammatory response to viruses, increases in bronchial responsiveness and up-regulation of intercellular adhesion molecule-1 expression in bronchial epithelium. In addition, exposure to allergens, especially seasonal allergens, in sensitized asthmatic individuals have been implicated in asthma attacks. Increased levels of exposure in sensitized asthmatics have been related to increases in hospital admissions and emergency room visits, increased bronchial hyperresponsiveness, increased levels of exhaled nitric oxide, lower levels of lung function, increased treatment requirements, and even increased mortality. In recent years studies have suggested that viruses and allergens may have a synergistic effect on individuals with asthma, thus having a greater influence on exacerbation rate together than either factor alone. Models of experimentally induced RV infection in both allergic and nonallergic individuals using bronchoalveolar lavage and segmental allergen challenge have helped researchers to investigate the possibility of an interaction between allergen sensitization, exposure, and virus infection and their role in the induction of an asthma exacerbation. This review aims to summarize the evidence supporting the role of viruses (in particular RV) as well as the role of, and interaction with, allergen sensitization and exposure on exacerbations of asthma.


Inclusion of patients in clinical trial analysis: the intention-to-treat principle.


Parental origin of chromosome 15 deletion in Prader-Willi syndrome.


title: Planning for the unexpected: Ebola virus, Zika virus, what's next?

text: Since 2000 we have witnessed global pandemics and public health emergencies of international concern. This review details which viruses are likely to caused further outbreaks and looks at the strategies and tools available to UK medical professionals to mitigate the threat posed.


title: Refining the approach to vaccines against influenza A viruses with pandemic potential.

text: Vaccination is the most effective strategy for prevention and control of influenza. Timely production and deployment of seasonal influenza vaccines is based on an understanding of the epidemiology of influenza and on global disease and virologic surveillance. Experience with seasonal influenza vaccines guided the initial development of pandemic influenza vaccines. A large investment in pandemic influenza vaccines in the last decade has resulted in much progress and a body of information that can now be applied to refine the established paradigm. Critical and complementary considerations for pandemic influenza vaccines include improved assessment of the pandemic potential of animal influenza viruses, proactive development and deployment of pandemic influenza vaccines, and application of novel platforms and strategies for vaccine production and administration.


Actions Taken by the Turkish Surgical Society on COVID-19.


title: Glycoconjugate glycans as viral receptors.

text: The carbohydrate parts of cell surface glycoproteins, glycolipids, and proteoglycans constitute receptors for many enveloped as well as non-enveloped human viruses. The majority of viral receptors of carbohydrate nature are negatively charged, including sulfated glycosaminoglycans (GAGs) or glycans containing sialic acid. Not uncommonly, virus-carbohydrate interactions are responsible for specific tissue tropism, where the affinity of influenza virus for glycans in the respiratory tract containing (a2-6)-linked sialic acid is an important example. Similarly, the number and spacing of sulfates may guide viruses to optimal GAG molecules, although this remains unproven on tissue level. A further understanding of structure and tissue distribution of carbohydrate virus receptors and their viral ligands is essential for elucidating the pathogenesis of such viruses. Also neutral glycans such as histo-blood group substances may function as virus receptors. Here, natural resistance to a given viral disease may occur in a human subpopulation due to lack of such receptors caused by deletion-mutants in critical human genes. As regards antiviral applications, the receptor-destroying enzymes, in contrast to receptor binding proteins, at the surface of, for example, influenza virus have proven to be an excellent target for intervention, which is why sialic acid analogues are now in clinical use both for prophylaxis and treatment.


docid: hukgtwlx

title: Murine coronavirus nonstructural protein p28 arrests cell cycle in G0/G1 phase.

text: Murine coronavirus mouse hepatitis virus (MHV) gene 1 encodes several nonstructural proteins. The functions are unknown for most of these nonstructural proteins, including p28, which is encoded at the 5' end of the MHV genome. Transient expression of cloned p28 in several different cultured cells inhibited cell growth, indicating that p28 expression suppressed cell proliferation. Expressed p28 was exclusively localized in the cytoplasm. Cell cycle analysis by flow cytometry demonstrated that p28 expression induced G(0)/G(1) cell cycle arrest. Characterization of various cellular proteins that are involved in regulating cell cycle progression demonstrated that p28 expression resulted in an accumulation of hypophosphorylated retinoblastoma protein (pRb), tumor suppressor p53, and cyclin-dependent kinase (Cdk) inhibitor p21(Cip1). Expression of p28 did not alter the amount of p53 transcripts yet increased the amount of p21(Cip1) transcripts, suggesting that p28 expression increased p53 stability and that p21(Cip1) was transcriptionally activated in a p53-dependent manner. Our present data suggest the following model of p28-induced G(0)/G(1) cell cycle arrest. Expressed cytoplasmic p28 induces the stabilization of p53, and accumulated p53 causes transcriptional upregulation of p21(Cip1). The increased amount of p21(Cip1) suppresses cyclin E/Cdk2 activity, resulting in the inhibition of pRb hyperphosphorylation. Accumulation of hypophosphorylated pRb thus prevents cell cycle progression from G(0)/G(1) to S phase.


Global Health Diplomacy: A Closer Look.


title: A leucine zipper structure present in the measles virus fusion protein is not required for its tetramerization but is essential for fusion.

text: The biological role of a leucine zipper motif present in the measles virus fusion (F) protein has been investigated. This motif is present in all paramyxovirus F proteins, all coronavirus spike proteins and many if not all retrovirus envelope proteins. By analogy to its role in certain transcription factors, it has been suggested that the motif may be responsible for the oligomerization of these viral membrane proteins. In this study, one, two or four heptadic leucines in the motif were substituted using site-directed mutagenesis. We found that fusion is prevented when all four heptadic leucines present in the motif are mutated whereas cellular transport and the oligomeric state of the F protein are unaffected.


title: Transfusion of blood products affects outcome in cardiac surgery.

text: There remains controversy as to when patients undergoing cardiac surgery should receive a transfusion and whether a low hematocrit and its treatment with a transfusion of red cells influences outcome. The data related to this controversy are reviewed. Although the risk of known viral transmission is currently low, stored red cells do not function normally, and each unit contains activated inflammatory cells and mediators. These changes cause limited oxygen release, impaired microcirculatory flow, and immune suppression. A number of studies have observed decreased survival associated with transfusions in trauma, coronary artery bypass grafting, and intensive care unit patients. Studies that show an adverse outcome associated with low hematocrit are not definitive, because they fail to distinguish between the impact of low hematocrit per se and the possible adverse effects of transfusion, for what the low hematocrit may simply be a surrogate. The observation that a low hematocrit is associated with an adverse outcome does not necessarily prove that "treatment" of the anemia with a red cell transfusion will improve the outcome. Stored platelets contain a highly activated mixture of platelets with storage lesions and inflammatory mediators. Two retrospective post hoc multifactorial analyses suggest that platelet transfusions are associated with substantial increased morbidity and mortality. Clearly, large prospective studies are required to define the proper trigger for blood product transfusion to balance the adverse effects of anemia and platelet deficiency or dysfunction with the adverse effects of transfusion of blood products on morbidity and mortality associated with cardiac surgery and anesthesia.


title: Nigrostriatal pathway degeneration in rats after intraperitoneal administration of proteasome inhibitor MG-132.

text: The proteins' ubiquitination and their further degradation by proteasomes are crucial for cell cycle regulation, transcription and DNA replication, inflammatory response, and apoptosis. Proteasome inhibitors have recently become considered as a promising method in cancer and inflammatory disease therapy. In this study, utilizing the rat model, we try to establish the influence of proteasome inhibitor MG-132: (1) on the basis of spontaneous and evoked locomotor activity and (2) on the condition of nigrostriatal projections eight weeks after MG-132 intraperitoneal administration. We also discuss the current status of knowledge about intraperitoneal administration of MG-132, a laboratory method that is being used more and more. Our results revealed a lack of motor abnormalities, but significant loss (20%) of substantia nigra pars compacta dopaminergic neurons after systemic MG-132 administration. This loss was accompanied by a corresponding decrease (8%) of density of dopaminergic terminals in dorsolateral striatum. Moreover, evidence of very limited but ongoing fibre degeneration within the dorsal striatum suggests that MG-132 severely disturbed the nigrostriatal pathway. In summary, intraperitoneal application of proteasome inhibitor MG-132, despite the encouraging results of experimental treatment and prevention of many pathological processes, should be used with caution because of the potential adverse effects on the structure of the central nervous system, especially elements of the nigrostriatal pathway.


title: How outbreaks of infectious disease are detected: a review of surveillance systems and outbreaks.

text: To learn how outbreaks of infectious disease are detected and to describe the entities and information systems that together function to identify outbreaks in the U.S., the authors drew on multiple sources of information to create a description of existing surveillance systems and how they interact to detect outbreaks. The results of this analysis were summarized in a system diagram. The authors reviewed a sample of recent outbreaks to determine how they were detected, with reference to the system diagram. The de facto U.S. system for detection of outbreaks consists of five components: the clinical health care system, local/state health agencies, federal agencies, academic/professional organizations, and collaborating governmental organizations. Primary data collection occurs at the level of clinical health care systems and local health agencies. The review of a convenience sample of outbreaks showed that all five components of the system participated in aggregating, analyzing, and sharing data. The authors conclude that the current U.S. approach to detection of disease outbreaks is complex and involves many organizations interacting in a loosely coupled manner. State and local health departments and the health care system are major components in the detection of outbreaks.


title: Cell surface expression of glycosylated, nonglycosylated, and truncated forms of a cytoplasmic protein pyruvate kinase.

text: The soluble cytoplasmic protein pyruvate kinase (PK) has been expressed at the cell surface in a membrane-anchored form (APK). The hybrid protein contains the NH2-terminal signal/anchor domain of a class II integral membrane protein (hemagglutinin/neuraminidase, of the paramyxovirus SV5) fused to the PK NH2 terminus. APK contains a cryptic site that is used for N-linked glycosylation but elimination of this site by site-specific mutagenesis does not prevent cell surface localization. Truncated forms of the APK molecule, with up to 80% of the PK region of APK removed, can also be expressed at the cell surface. These data suggest that neither the complete PK molecule nor its glycosylation are necessary for intracellular transport of PK to the cell surface, and it is possible that specific signals may not be needed in the ectodomain of this hybrid protein to specify cell surface localization.


title: In vivo repair of 3'-end deletions in a TCV satellite RNA may involve two abortive synthesis and priming events.

text: RNA viruses that do not have the stabilizing features of poly(A) tails or amino acids covalently linked to their 3' ends must develop other means for protecting or repairing their genomes from damage caused by cellular RNases. We previously found that deletions in the single-stranded tails of a satellite RNA (sat-RNA D) associated with turnip crinkle virus are repaired in vivo (C. D. Carpenter and A. E. Simon, 1996, J. Virol. 70, 478-486). We now extend this analysis to show that sat-RNA D transcripts with 3'-end deletions of 5 bases give rise to wild-type sat-RNA, while deletions of 6 to 11 bases result in sat-RNA with additional deletions to the -14 position joined to internal TCV genomic RNA (or other) sequence followed by replacement of the terminal C1-2UGC1-3 motif. In addition, we have determined that the selection of internal TCV sequence used in the repair of sat-RNA D 3' ends is not random and generation of these short TCV segments likely involves primer-mediated synthesis of abortive products facilitated by base-pairing between internal regions of TCV genomic RNA and oligoribonucleotides generated by abortive cycling from the 3' end of the TCV genome.


title: Capitalizing on capabilities.

text: By making the most of organizational capabilities--employees' collective skills and fields of expertise--you can dramatically improve your company's market value. Although there is no magic list of proficiencies that every organization needs in order to succeed, the authors identify 11 intangible assets that well-managed companies tend to have: talent, speed, shared mind-set and coherent brand identity, accountability, collaboration, learning, leadership, customer connectivity, strategic unity, innovation, and efficiency. Such companies typically excel in only three of these capabilities while maintaining industry parity in the other areas. Organizations that fall below the norm in any of the 11 are likely candidates for dysfunction and competitive disadvantage. So you can determine how your company fares in these categories (or others, if the generic list doesn't suit your needs), the authors explain how to conduct a "capabilities audit," describing in particular the experiences and findings of two companies that recently performed such audits. In addition to highlighting which intangible assets are most important given the organization's history and strategy, this exercise will gauge how well your company delivers on its capabilities and will guide you in developing an action plan for improvement. A capabilities audit can work for an entire organization, a business unit, or a region--indeed, for any part of a company that has a strategy to generate financial or customer-related results. It enables executives to assess overall company strengths and weaknesses, senior leaders to define strategy, midlevel managers to execute strategy, and frontline leaders to achieve tactical results. In short, it helps turn intangible assets into concrete strengths.


title: Receptor-independent spread of a highly neurotropic murine coronavirus JHMV strain from initially infected microglial cells in mixed neural cultures.

text: Although neurovirulent mouse hepatitis virus (MHV) strain JHMV multiplies in a variety of brain cells, expression of its receptor carcinoembryonic antigen cell adhesion molecule 1 (CEACAM 1) (MHVR) is restricted only in microglia. The present study was undertaken to clarify the mechanism of an extensive JHMV infection in the brain by using neural cells isolated from mouse brain. In contrast to wild-type (wt) JHMV, a soluble-receptor-resistant mutant (srr7) infects and spreads solely in an MHVR-dependent fashion (F. Taguchi and S. Matsuyama, J. Virol. 76:950-958, 2002). In mixed neural cell cultures, srr7 infected a limited number of cells and infection did not spread, although wt JHMV induced syncytia in most of the cells. srr7-infected cells were positive for GS-lectin, a microglia marker. Fluorescence-activated cell sorter analysis showed that about 80% of the brain cells stained with anti-MHVR antibody (CC1) were also positive for GS-lectin. Pretreatment of those cells with CC1 prevented virus attachment to the cell surface and also blocked virus infection. These results show that microglia express functional MHVR that mediates JHMV infection. As expected, in microglial cell-enriched cultures, both srr7and wt JHMV produced syncytia in a majority of cells. Treatment with CC1 of mixed neural cell cultures and microglia cultures previously infected with wt virus failed to block the spread of infection, indicating that wt infection spreads in an MHVR-independent fashion. Thus, the present study indicates that microglial cells are the major population of the initial target for MHV infection and that the wt spreads from initially infected microglia to a variety of cells in an MHVR-independent fashion.


title: Mycoplasma pneumoniae and its role in asthma.

text: Mycoplasma pneumoniae (M pneumoniae), primarily recognised as a causative agent of community-acquired pneumonia has recently been linked to asthma. An infection with M pneumoniae may precede the onset of asthma or exacerbate asthma symptoms. Chronic infection with M pneumoniae has been suspected to play a part in some patients with asthma. The role of immunoglobulin E-related hypersensitivity and induction of T helper type 2 immune response leading to inflammatory response in M pneumoniae-infected patients with asthma have also been proposed. Use of macrolides in reducing asthma symptoms only in M pneumoniae-infected patients supports the use of macrolides in patients with asthma having M pneumoniae infection. As macrolides are both antimicrobial and anti-inflammatory drugs, the therapeutic role of their biphasic nature in reducing asthma symptoms needs further attention in clinical research.


title: Taking stock of the first 133 MERS coronavirus cases globally--Is the epidemic changing?

text: Since June 2012, 133 Middle East respiratory syndrome coronavirus (MERS-CoV) cases have been identified in nine countries. Two time periods in 2013 were compared to identify changes in the epidemiology. The case-fatality risk (CFR) is 45% and is decreasing. Men have a higher CFR (52%) and are over-represented among cases. Thirteen out of 14 known primary cases died. The sex-ratio is more balanced in the latter period. Nosocomial transmission was implied in 26% of the cases.


2004 update of BTS pneumonia guidelines: what's new?


title: Health-related quality of life and the prevalence of post-traumatic stress disorder among Crimean-Congo hemorrhagic fever survivors.

text: Crimean-Congo hemorrhagic fever (CCHF) is a potentially fatal infectious disease, and it is endemic in Turkey. Patients are placed in isolation when hospitalized, and some may require blood transfusions. Moreover, some patients may require admission to intensive care units (ICU). CCHF is not a recurrent disease, and relapses are not expected. Therefore, no medical follow-up is conducted on recovery from CCHF. In this study, health-related quality of life (HRQL) and the presence of post-traumatic stress disorder (PTSD) among CCHF survivors were evaluated 12 months after recovery from the disease. PTSD diagnosis was established by DSM-IV-TR criteria and HRQL was investigated by using the Medical Outcomes Study Short Form 36. This study included 54 patients. Our results showed that 48.1% of the patients had PTSD symptoms and 18.5% had PTSD. PTSD incidence was higher among patients who required an ICU stay, who had bleeding, and who required blood transfusion. In addition, 4 out of 8 dimensions of HRQL were impaired. However, none of these patients admitted psychiatric problems to health care professionals. Our findings revealed that periodic psychiatric evaluation should be performed on CCHF patients, and they should be provided medical support, if required.


docid: bsdxieol

title: Multiplex real-time reverse transcription-polymerase chain reaction for the detection of three viruses associated with poult enteritis complex: turkey astrovirus, turkey coronavirus, and turkey reovirus.

text: Poult enteritis complex (PEC) is an economically important disease of young turkeys characterized by diarrhea, poor weight gain, and, in some cases, high mortality. Although PEC is considered to be a polymicrobial disease, numerous viruses, including turkey coronavirus (TCV), turkey astrovirus type 2 (TAstV-2), and avian reoviruses (ARVs), have been associated with PEC-like disease. Real-time reverse transcription-polymerase chain reaction (RRT-PCR), a highly sensitive and specific detection method for viral RNA, was developed in a multiplex format for the simultaneous detection of TAstV-2 and TCV and for the detection of two genetic types of ARV. Assay sensitivity was determined using in vitro transcribed RNA and varied by target between 150 gene copies for TAstV-2 alone and 2200 gene copies for TCV when multiplexed. Virus detection was evaluated with samples collected from poults inoculated at 1 day of age with each of the viruses. Cloacal swabs and intestinal samples were obtained at 1, 2, 3, 4, 6, 9, 14, 17, and 21 days after inoculation, processed, and tested for virus detection by RRT-PCR Cloacal swabs from TAstV-2- and TCV-infected poults were shown to have sensitivity for virus detection similar to that of intestinal samples when compared directly. ARV detection by RRT-PCR was compared with virus isolation and had similar sensitivity.


title: Optimal word sizes for dissimilarity measures and estimation of the degree of dissimilarity between DNA sequences.

text: MOTIVATION Several measures of DNA sequence dissimilarity have been developed. The purpose of this paper is 3-fold. Firstly, we compare the performance of several word-based or alignment-based methods. Secondly, we give a general guideline for choosing the window size and determining the optimal word sizes for several word-based measures at different window sizes. Thirdly, we use a large-scale simulation method to simulate data from the distribution of SK-LD (symmetric Kullback-Leibler discrepancy). These simulated data can be used to estimate the degree of dissimilarity beta between any pair of DNA sequences. RESULTS Our study shows (1) for whole sequence similiarity/dissimilarity identification the window size taken should be as large as possible, but probably not >3000, as restricted by CPU time in practice, (2) for each measure the optimal word size increases with window size, (3) when the optimal word size is used, SK-LD performance is superior in both simulation and real data analysis, (4) the estimate beta of beta based on SK-LD can be used to filter out quickly a large number of dissimilar sequences and speed alignment-based database search for similar sequences and (5) beta is also applicable in local similarity comparison situations. For example, it can help in selecting oligo probes with high specificity and, therefore, has potential in probe design for microarrays. AVAILABILITY The algorithm SK-LD, estimate beta and simulation software are implemented in MATLAB code, and are available at http://www.stat.ncku.edu.tw/tjwu


EBOLA: A PUBLIC HEALTH AND LEGAL PERSPECTIVE.


docid: dpsbgxzf

title: Speech intelligibility assessment of protective facemasks and air-purifying respirators.

text: Speech Intelligibility (SI) is the perceived quality of sound transmission. In healthcare settings, the ability to communicate clearly with coworkers, patients, etc., is crucial to quality patient care and safety. The objectives of this study were to: (1) assess the suitability of the Speech Transmission Index (STI) methods for testing reusable and disposable facial and respiratory personal protective equipment (protective facemasks [PF], N95 filtering facepiece respirators [N95 FFR], and elastomeric half-mask air-purifying respirators [EAPR]) commonly worn by healthcare workers; (2) quantify STI levels of these devices; and (3) contribute to the scientific body of knowledge in the area of SI. SI was assessed using the STI under two experimental conditions: (1) a modified version of the National Fire Protection Association 1981 Supplementary Voice Communications System Performance Test at a Signal to Noise Ratio (SNR) of -15 (66 dBA) and (2) STI measurements utilizing a range of modified pink noise levels (52.5 dBA (-2 SNR) - 72.5 dBA (+7 SNR)) in 5.0 dBA increments. The PF models (Kimberly Clark 49214 and 3 M 1818) had the least effect on SI interference, typically deviating from the STI baseline (no-mask condition) by 3% and 4% STI, respectively. The N95FFR (3 M 1870, 3 M 1860) had more effect on SI interference, typically differing from baseline by 13% and 17%, respectively, for models tested. The EAPR models (Scott Xcel and North 5500) had the most significant impact on SI, differing from baseline by 42% for models tested. This data offers insight into the performance of these apparatus with respect to STI and may serve as a reference point for future respirator design considerations, standards development, testing and certification activities.


title: Expanding the roles of hospitalist physicians to include public health.

text: Several years after the inception of the hospitalist movement, hospitalist roles have evolved in breadth and sophistication. Although public health is not formally recognized or previously described as an arena for hospitalists, hospitalists are often engaged in public health practice. This article attempts to alert hospitalists to the potential to make contributions to the field of public health and defines the public health skills that can positively affect the lives of their patients and the communities they serve. In a public health role, hospitalists may improve the quality of inpatient care. This article reviews how public health and hospital-based practices have already intersected and proposes further development within this discipline. In our ever-changing health care system, hospitalists play key roles in the central public health domains of assessment, assurance, and policy development. Insightful hospitalists will recognize and embrace these responsibilities in caring for patients and society.


Cardiovascular care in sub-Saharan Africa during the COVID-19 crisis: lessons from the global experience.


title: Concentration-dependent mode of interaction of angiotensin II receptor blockers with uric acid transporter.

text: Serum uric acid (SUA) is currently recognized as a risk factor for cardiovascular disease. It has been reported that an angiotensin II receptor blocker (ARB), losartan, decreases SUA level, whereas other ARBs, such as candesartan, have no lowering effect. Because the renal uric acid transporter (URAT1) is an important factor controlling the SUA level, we examined the involvement of URAT1 in those differential effects of various ARBs on SUA level at clinically relevant concentrations. This study was done by using URAT1-expressing Xenopus oocytes. Losartan, pratosartan, and telmisartan exhibited cis-inhibitory effects on the uptake of uric acid by URAT1, whereas at higher concentrations, only telmisartan did, and these ARBs reduced the uptake in competitive inhibition kinetics. On the other hand, candesartan, EXP3174 [2-n-butyl-4-chloro-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yI)methyl]imidazole-5-carboxylic acid] (a major metabolite of losartan), olmesartan, and valsartan were not inhibitory. Preloading of those ARBs in the oocytes enhanced the URAT1-mediated uric acid uptake, showing a trans-stimulatory effect. The present study is a first demonstration of the differential effects of ARBs on URAT1 that some ARBs are both cis-inhibitory and trans-stimulatory, depending on concentration, whereas others exhibit either a trans-stimulatory or cis-inhibitory effect alone, which could explain the clinically observed differential effects of ARBs on SUA level. Furthermore, it was found that such differential effects of ARBs on URAT1 could be predicted from the partial chemical structures of ARBs, which will be useful information for the appropriate use and development of ARBs without an increase of SUA.


title: Role of nitric oxide in pathogenesis of herpes simplex virus encephalitis in rats.

text: The role of nitric oxide (NO) in the pathogenesis of viral encephalitis was investigated by using an experimental model of herpes simplex virus type 1 (HSV-1) encephalitis in Lewis rats. The expression of inducible NO synthase (iNOS) mRNA determined by Northern blotting was observed first in the olfactory bulb and the brain stem on day 5 after intranasal inoculation of HSV-1, and thereafter iNOS mRNA was detected in other brain regions, i.e., cerebrum and cerebellum. In various parts of the brain, excessive NO production was identified by electron spin resonance spectroscopy. The temporal and spatial patterns of iNOS expression coincided with those of viral propagation, as demonstrated by polymerase chain reaction for HSV-1 gene expression as well as by the plaque-forming assay. Immunohistochemical study determined that iNOS was localized mainly in monocyte-derived macrophages. Treatment of virus-infected animals with the NOS inhibitor Nomega-monomethyl-l-arginine (l-NMMA), but not Nomega-monomethyl-d-arginine, significantly ameliorated not only clinical symptoms such as paralysis and seizures but also mortality. Virus yield from brain tissue was not affected by l-NMMA treatment. It is of interest that increased expression of the antioxidant enzyme heme oxygenase-1 was observed in the HSV-1-infected brain; this increased expression was strongly inhibited by l-NMMA treatment. These data suggest that the high level of NO produced by iNOS is a pathogenic factor in HSV-1-induced encephalitis in rats.


Circe, Cassandra, and the trojan pigs: xenotransplantation.


title: [Emergency Medical Services: COVID-19 crisis].

text: The COVID-19 epidemic required rapid and frequent adaptations from the prehospital emergency medical services (EMS). The exposure of EMS providers is significant, particularly during procedures at risk of aerosolization such as advanced airways management or cardiopulmonary resuscitation. EMS personal need to be equipped with appropriate personal protective equipment and trained in its use. Interhospital transfers from COVID-19 patients are complex and involve mainly intubated patients. The possible shortage of resources may motivate the implementation of dedicated pre-hospital triage and orientation recommendations, which should be consistent with the hospital processes.


title: Transmission of avian influenza A(H7N9) virus from father to child: a report of limited person-to-person transmission, Guangzhou, China, January 2014.

text: We investigated a possible person-to-person transmission within a family cluster of two confirmed influenza A(H7N9) patients in Guangzhou, China. The index case, a man in his late twenties, worked in a wet market that was confirmed to be contaminated by the influenza A(H7N9) virus. He developed a consistent fever and severe pneumonia after 4 January 2014. In contrast, the second case, his five-year-old child, who only developed a mild disease 10 days after disease onset of the index case, did not have any contact with poultry and birds but had unprotected and very close contact with the index case. The sequences of the haemagglutinin (HA) genes of the virus stains isolated from the two cases were 100% identical. These findings strongly suggest that the second case might have acquired the infection via transmission of the virus from the sick father. Fortunately, all 40 close contacts, including the other four family members who also had unprotected and very close contact with the cases, did not acquire influenza A(H7N9) virus infection, indicating that the person-to-person transmissibility of the virus remained limited. Our finding underlines the importance of carefully, thoroughly and punctually following-up close contacts of influenza A(H7N9) cases to allow detection of any secondary cases, as these may constitute an early warning signal of the virus's increasing ability to transmit from person-to-person.


title: Characterization of a variant virus selected in rat brains after infection by coronavirus mouse hepatitis virus JHM.

text: The intracerebral inoculation of Lewis rats with the murine coronavirus MHV-JHM leads in the majority of animals to acute encephalitis and death within 14 days. Viral RNAs isolated from the brains of animals 5 to 7 days after infection were compared by Northern blot analysis with the RNAs produced during the lytic infection of Sac(-) or DBT cells with wild-type MHV-JHM (wt virus). Reproducibly, the subgenomic mRNAs 2 and 3 but no other viral RNAs were significantly larger in the brain-derived material. All viruses isolated from infected brain material displayed and maintained this altered mRNA profile when cultivated in Sac(-) or DBT cells. A virus isolated from the infected brain material, MHV-JHM clone 2 (cl-2 virus), has been further characterized. This isolate grew in tissue culture and induced cytopathic effects comparable to those induced by wt virus. However, the mRNAs 2 and 3 produced in cl-2 virus-infected cells had molecular weights ca. 150,000 larger than those produced in cells infected with wt virus. There was no detectable difference in genome-sized RNA (mRNA 1) or subgenomic mRNAs 4, 5, 6, and 7 as determined by electrophoresis in agarose gels. T1-resistant oligonucleotide analysis of genomic RNA revealed one additional and one missing oligonucleotide in the fingerprint of cl-2 virus compared with wt virus. The oligonucleotide fingerprints of intracellular mRNA 3 were identical for both viruses. Pulse-labeling with [35S]methionine in the presence of tunicamycin showed that the primary translation product of mRNA 3, the E2 apoprotein, was ca. 15,000 larger in molecular weight in cl-2 virus-infected cells. These data show that viruses with larger mRNAs 2 and 3 (the latter encoding an altered E2 glycoprotein) are selected for multiplication in rat brains. Mechanisms for the generation of such variants and the possible nature of their selective advantage are considered.


title: Association of RANTES with the replication of severe acute respiratory syndrome coronavirus in THP-1 cells.

text: BACKGROUND Severe acute respiratory syndrome (SARS) is a novel infectious disease which is characterized by an overaggressive immune response. Chemokines are important inflammatory mediators and regulate disease due to viral infection. In previous study, we found that SARS-CoV has the ability to replicate in mononuclear cells. In present work, we sought to characterize the replication of SARS-CoV at the presence of RANTES in THP-1 cells. METHODS To determine whether RANTES play an role in the process of SARS, THP-1 cells were incubated with heat-inactivated SARS-CoV and ELISA was used to test RANTES levels in the supernatants; Then the effect of dexamethasone on the induced secretion was evaluated. Real-time PCR was used to investigate the effort of RANTES on the replication of SARS-CoV in vitro. Macrophages, induced by THP-1 cells, were used as cell model. FINDINGS Inactive SARS-CoV could induce THP-1 cells secret RANTES and this increase effect could not be suppressed by DXM. RANTES itself could inhibit the replication of SARS-CoV in THP-1 cells when it was added into the culture before or at the same time with the virus; No inhibition effect was shown when RANTES were added into the culture after SARS-CoV infected the cells.


title: [Evaluation on the functions and cost of 'fever clinics' during the period of severe acute respiratory syndrome epidemics in Beijing].

text: OBJECTIVE To identify the experiences and lessons learned on 'fever clinics' during the severe acute respiratory syndrome (SARS) epidemic in Beijing and to propose a better model in monitoring SARS to fit the 'fever clinics' into current situation. METHODS Both qualitative and quantitative methods were used in data collection and analyses. Quantitative surveys would include 1. The setting, functions and administration of current 63 'fever clinics' in Beijing; 2. Survey on patients with fever who had visited 'fever clinics' and randomly selected from the 63 fever clinics; 3. Survey on physicians working in the 'fever clinics'. Qualitative studies would include discussion or interview with administrators, physicians working in the 'fever clinics' and field studies on 23 randomly selected 'fever clinics' as well as telephone interview to the staff working in the hospitals that did not have the 'fever clinics'. RESULTS A couple of significant problems raised during the study including: 1. Low coverage of current surveillance system. 89% of the hospitals were not covered by the surveillance system which reflecting the misjudgment on the patients with fever that they would only attend 'fever clinics' to seek for medical help. The fact was that most of the hospitals where 'fever clinics' had not been set also received patients with fever. 2. Information related to patients with fever needs to improve regarding its completeness and accuracy. 3. Significant unbalance in daily cost and effectiveness in most of the 'fever clinics' was noticed. CONCLUSION 'Fever clinics' needs to be adjusted to meet the possible SARS epidemic in coming winter and spring. Short-term and long-term suggestions were proposed regarding SARS monitoring through the functions of 'fever clinics' in Beijing.


title: CD8+ T-cell epitopes within the surface glycoprotein of a neurotropic coronavirus and correlation with pathogenicity.

text: CD8+ T cells with cytotoxic activity against the surface glycoprotein (S) of mouse hepatitis virus, strain JHM, have been identified in the central nervous system (CNS) of both acutely and chronically infected C57BL/6 mice. In this report, two specific epitopes recognized by these CNS-derived cells were identified, using a panel of peptides chosen because they conformed to the allele-specific binding motif for MHC class I H-2Kb and H-2Db. The active peptides encompassed residues 510 to 518 (CSLWNGPHL, H-2Db) and 598 to 605 (RCQIFANI, H-2Kb). Both epitopes are located within the region of the S protein previously shown to be prone to deletion after passage in animals. These deleted strains are generally less neurovirulent than the wild-type virus but still are able to cause demyelination. Since C57BL/6 mice become persistently infected more commonly than many other strains of mice, these data are consistent with a role for CD8+ T-cell escape mutants in the pathogenesis of the demyelinating disease. This is the first report of CD8+ T-cell epitope localization within the S protein, the protein most strongly implicated thus far in pathogenesis in the host.


title: In vivo and in vitro models of demyelinating diseases, XX: Replication of coronaviruses in primary neural cultures from genetically resistant and susceptible mice.

text: Resistance of SJL mice to JHMV could be associated with explanted oligodendrocytes and astrocytes in primary neural cultures from newborn mice. The restriction demonstrated is not at the stage of adsorption, uptake by the host or RNA synthesis and does not occur with the serorelated MHV3 strain. Experiments with neural cells from F1 hybrid mice bred from resistant and sensitive parents show that resistance is a recessive trait. It is hypothesized that the defect may involve proteolysis at the cell surface, but to date no clear cut experimental data have been obtained to substantiate this idea. In more general terms our in-vitro observations demonstrate that resistance of SJL mice pertains to both embryonic and newborn animals and involves neural and non neural cell types. Thus, the SJL restriction of JHMV, evident at the cellular level, does not involve an age-related maturation process associated with rat and mouse oligodendrocytes studied previously (1, 14).


title: S1 gene sequence heterogeneity of a pathogenic infectious bronchitis virus strain and its embryo-passaged, attenuated derivatives.

text: Infectious bronchitis virus CK/CH/LDL/97I was attenuated by serial passage in chicken embryos. Virus of passage 115 was attenuated as determined by clinical response to inoculation to 15-day-old specific pathogen free chickens. The vaccination-challenge test showed that the attenuated passage 115 virus could afford protection against the homologous pathogenic virus, passage 5, by the clinical response. Based on the sequence analysis and comparison of the S1 gene, both the pathogenic and attenuated CK/CH/LDL/97I viruses were populations that each included at least two subpopulations. Also, from analysis of the amino acid and nucleotide sequences of S1 gene, we speculate that recombination between the minor and dominant subpopulations plus accumulation of mutations in the S1 region of pathogenic passage 5 might lead to the formation of the embryo-passaged, attenuated passage 115.


title: Pathogen Inactivation of Platelet and Plasma Blood Components for Transfusion Using the INTERCEPT Blood System™

text: BACKGROUND: The transmission of pathogens via blood transfusion is still a major threat. Expert conferences established the need for a pro-active approach and concluded that the introduction of a pathogen inactivation/reduction technology requires a thorough safety profile, a comprehensive pre-clinical and clinical development and an ongoing hemovigilance program. MATERIAL AND METHODS: The INTERCEPT Blood System utilizes amotosalen and UVA light and enables for the treatment of platelets and plasma in the same device. Preclinical studies of pathogen inactivation and toxicology and a thorough program of clinical studies have been conducted and an active he-movigilance-program established. RESULTS: INTERCEPT shows robust efficacy of inactivation for viruses, bacteria (including spirochetes), protozoa and leukocytes as well as large safety margins. Furthermore, it integrates well into routine blood center operations. The clinical study program demonstrates the successful use for very diverse patient groups. The hemovigilance program shows safety and tolerability in routine use. Approximately 700,000 INTERCEPT-treated products have been transfused worldwide. The system is in clinical use since class III CE-mark registration in 2002. The safety and efficacy has been shown in routine use and during an epidemic. CONCLUSION: The INTERCEPT Blood System for platelets and plasma offers enhanced safety for the patient and protection against transfusion-transmitted infections.


National Notifiable Diseases Surveillance System, 1 January to 31 March 2014.


title: SARS coronavirus and apoptosis.

text: 1. The adenovirus-mediated overexpression of SARS coronavirus (SARS-CoV) spike protein (S) and its C-terminal domain (S2) induce apoptosis in Vero E6 cells. 2. Such apoptosis in Vero E6 cells is time- and dose-dependent. 3. The adenovirus-mediated overexpression of SARS-CoV N-terminal domain (S1) and other structural proteins, including E,M and N protein, do not induce apoptosis.


Extensively drug-resistant tuberculosis: an isolation order, public health powers, and a global crisis.


title: Sutureless total thyroidectomy: a safe and cost-effective alternative.

text: BACKGROUND Advanced vessel sealing devices provide an alternative to conventional ligation techniques for thyroidectomy. To date, most studies have been inadequately powered to explore differences in the infrequent post-operative complications following thyroidectomy. This study is designed to compare the outcomes of sutureless thyroidectomy and conventional thyroidectomy for recurrent laryngeal nerve (RLN) injury, permanent hypoparathyroidism, and haematoma formation. METHODS A cohort study of consecutive patients undergoing total thyroidectomy using conventional versus sutureless techniques was performed. Sutureless thyroidectomy was performed using either Ligasure Precise (Covidien) or Harmonic Focus (Johnson and Johnson) devices. The primary outcome measures were post-operative haemorrhage, permanent RLN injury and hypoparathyroidism. Secondary outcome measures were operative time, temporary hypoparathyroidism and vocal cord dysfunction. A cost minimization analysis comparing the two techniques was performed. RESULT From January 2006 to July 2009, 1935 consecutive patients underwent total thyroidectomy. Of these, 772 underwent conventional thyroidectomy and 1163 were performed using a sutureless technique. The mean operative time was significantly lower in the sutureless group (71 versus 86 min, P = 0.02). There was no difference in the post-operative complications of haematoma (0.78% conventional versus 1.12% sutureless, P = 0.46), permanent hypoparathyroidism (1.30% conventional versus 0.52% sutureless, P = 0.06) or permanent RLN injury (0.26% conventional versus 0.52% sutureless, P = 0.39). There was an overall cost saving of AUD$14,300 per 100 total thyroidectomy cases performed using the sutureless technique. CONCLUSIONS Sutureless thyroidectomy is a safe and efficient way of performing total thyroidectomy and has the potential to reduce operating room costs.


Characterization of attenuated mutants of MHV3: importance of the E2 protein in organ tropism and infection of isolated liver cells.


title: Update: Severe acute respiratory syndrome--United States, 2003.

text: CDC continues to work with state and local health departments, the World Health Organization (WHO), and other partners to investigate cases of severe acute respiratory syndrome (SARS). During November 1, 2002-April 30, 2003, a total of 5,663 SARS cases were reported to WHO from 26 countries, including the United States; 372 deaths (case-fatality proportion: 6.6%) have been reported. This report updates information on reported SARS cases among U.S. residents and provides an overview regarding CDC's issuance of travel alerts and advisories.


title: Neuropilin-1 modulates interferon-γ-stimulated signaling in brain microvascular endothelial cells.

text: Inflammatory response of blood-brain barrier (BBB) endothelial cells plays an important role in pathogenesis of many central nervous system inflammatory diseases, including multiple sclerosis; however, the molecular mechanism mediating BBB endothelial cell inflammatory response remains unclear. In this study, we first observed that knockdown of neuropilin-1 (NRP1), a co-receptor of several structurally diverse ligands, suppressed interferon-γ (IFNγ)-induced C-X-C motif chemokine 10 expression and activation of STAT1 in brain microvascular endothelial cells in a Rac1-dependent manner. Moreover, endothelial-specific NRP1-knockout mice, VECadherin-Cre-ERT2/NRP1flox/flox mice, showed attenuated disease progression during experimental autoimmune encephalomyelitis, a mouse neuroinflammatory disease model. Detailed analysis utilizing histological staining, quantitative PCR, flow cytometry and magnetic resonance imaging demonstrated that deletion of endothelial NRP1 suppressed neuron demyelination, altered lymphocyte infiltration, preserved BBB function and decreased activation of the STAT1-CXCL10 pathway. Furthermore, increased expression of NRP1 was observed in endothelial cells of acute multiple sclerosis lesions. Our data identify a new molecular mechanism of brain microvascular endothelial inflammatory response through NRP1-IFNγ crosstalk that could be a potential target for intervention of endothelial cell dysfunction in neuroinflammatory diseases.


title: Identification of severe acute respiratory syndrome in Canada.

text: BACKGROUND Severe acute respiratory syndrome (SARS) is a condition of unknown cause that has recently been recognized in patients in Asia, North America, and Europe. This report summarizes the initial epidemiologic findings, clinical description, and diagnostic findings that followed the identification of SARS in Canada. METHODS SARS was first identified in Canada in early March 2003. We collected epidemiologic, clinical, and diagnostic data from each of the first 10 cases prospectively as they were identified. Specimens from all cases were sent to local, provincial, national, and international laboratories for studies to identify an etiologic agent. RESULTS The patients ranged from 24 to 78 years old; 60 percent were men. Transmission occurred only after close contact. The most common presenting symptoms were fever (in 100 percent of cases) and malaise (in 70 percent), followed by nonproductive cough (in 100 percent) and dyspnea (in 80 percent) associated with infiltrates on chest radiography (in 100 percent). Lymphopenia (in 89 percent of those for whom data were available), elevated lactate dehydrogenase levels (in 80 percent), elevated aspartate aminotransferase levels (in 78 percent), and elevated creatinine kinase levels (in 56 percent) were common. Empirical therapy most commonly included antibiotics, oseltamivir, and intravenous ribavirin. Mechanical ventilation was required in five patients. Three patients died, and five have had clinical improvement. The results of laboratory investigations were negative or not clinically significant except for the amplification of human metapneumovirus from respiratory specimens from five of nine patients and the isolation and amplification of a novel coronavirus from five of nine patients. In four cases both pathogens were isolated. CONCLUSIONS SARS is a condition associated with substantial morbidity and mortality. It appears to be of viral origin, with patterns suggesting droplet or contact transmission. The role of human metapneumovirus, a novel coronavirus, or both requires further investigation.


title: Trypanosoma evansi and "Candidatus Mycoplasma haemolamae" Co-Infection in One-Humped Camel (Camelus dromedarius) from the Northwest of Iran: A Case Report.

text: A 4-year-old male one-humped camel (Camelus dromedarius) was referred to Veterinary Teaching Hospital of Urmia University, Iran in 2017 with anorexia, weakness, depression and pale mucosa. Decreased red blood cell count, packed cell volume and hemoglobin concentration were detected by complete blood cell count. In Giemsa-stained peripheral blood smears Trypanosoma spp. trypomastigotes scattered between erythrocytic spaces and Mycoplasma-like organisms were observed attached to the surface of erythrocytes. Species-specific PCR assay confirmed T. evansi and Candidatus Mycoplasma haemolamae (CMhl) co-infection. Administration of diminazene aceturate, oxytetracycline 20%, flunixin meglumine and phosphorus-vitamin B12 were not effective in treatment. Hemoplasmosis should be considered as an important differential diagnosis of conditions associated with hemolytic anemia in camel.


New vision, new paradigm: health and wealth for all by 2100--or for no one.


title: Immunity to transmissible (coronaviral) enteritis of turkeys (bluecomb).

text: Turkey flocks recovering from natural and laboratory induced coronaviral enteritis developed lifelong immunity. Virus neutralization tests indicated that neutralization capacity of serums from recovered turkeys was low. One-way cross challenge test using turkeys inoculated with various bluecomb isolates revealed close antigenic relationship or antigenic identity among bluecomb isolates. The controlled application of intestinal preparations containing coronavirus as a vaccination procedure had value in developing active lasting immunity but it has limitations in areas that are attempting to eliminate the disease by a depopulation program. Killed vaccines injected parenterally did not produce a detectable immunity.


title: A major determinant for membrane protein interaction localizes to the carboxy-terminal domain of the mouse coronavirus nucleocapsid protein.

text: The two major constituents of coronavirus virions are the membrane (M) and nucleocapsid (N) proteins. The M protein is anchored in the viral envelope by three transmembrane segments flanked by a short amino-terminal ectodomain and a large carboxy-terminal endodomain. The M endodomain interacts with the viral nucleocapsid, which consists of the positive-strand RNA genome helically encapsidated by N protein monomers. In previous work with the coronavirus mouse hepatitis virus (MHV), a highly defective M protein mutant, MDelta2, was constructed. This mutant contained a 2-amino-acid carboxy-terminal truncation of the M protein. Analysis of second-site revertants of MDelta2 revealed mutations in the carboxy-terminal region of the N protein that compensated for the defect in the M protein. To seek further genetic evidence corroborating this interaction, we generated a comprehensive set of clustered charged-to-alanine mutants in the carboxy-terminal domain 3 of N protein. One of these mutants, CCA4, had a highly defective phenotype similar to that of MDelta2. Transfer of the CCA4 mutation into a partially diploid MHV genome showed that CCA4 was a loss-of-function mutation rather than a dominant-negative mutation. Analysis of multiple second-site revertants of CCA4 revealed mutations in both the M protein and the N protein that could compensate for the original lesion in N. These data more precisely define the region of the N protein that interacts with the M protein. Further, we found that fusion of domain 3 of the N protein to the carboxy terminus of a heterologous protein caused it to be incorporated into MHV virions.


title: [Concerns and demands regarding COVID-19. Survey of health personnel].

text: The COVID-19 pandemic affected the organization of health services and had consequences for health teams, according to the pre-existing safety and working conditions. During the first week of April 2020, a cross sectional study was carried out with a qualitative-quantitative approach. The aim was to explore the conditions determining the organizational climate: leadership, communication, institutional resources, cohesion/conflict management, and training; and how these were perceived by health personnel to deal with the pandemic. A total of 5670 healthcare workers participated in an online survey and 50 were interviewed, from all subsectors of the Argentinean health system (public, private and union-health insurance); 72.9% were women, 51.4% were physicians, and the predominant age group was under 40 years. In the qualitative sample (interviews), 52% were men, 62% were physicians, and the average age was 44.8 years. The dimensions of the organizational climate were stratified and five independent predictors of perception of conditions were identified: age, gender, tasks performed, health system subsector, and jurisdiction. The condition most frequently perceived as inadequate were the inaccessibility of institutional resources and the access to personal protective equipment was a major concern. Claims included the need of institutional strategies to support healthcare workers and of a clear and uniform communication. In conclusion, at the time of the study, the health personnel perceived serious deficits in their organizations regarding the conditions necessary to confront COVID-19, with differences among subsectors of the health system.


title: Altered pathogenesis of porcine respiratory coronavirus in pigs due to immunosuppressive effects of dexamethasone: implications for corticosteroid use in treatment of severe acute respiratory syndrome coronavirus.

text: The pathogenesis and optimal treatments for severe acute respiratory syndrome (SARS) are unclear, although corticosteroids were used to reduce lung and systemic inflammation. Because the pulmonary pathology of porcine respiratory coronavirus (PRCV) in pigs resembles SARS, we used PRCV as a model to clarify the effects of the corticosteroid dexamethasone (DEX) on coronavirus (CoV)-induced pneumonia. Conventional weaned pigs (n = 130) in one of four groups (PRCV/phosphate-buffered saline [PBS] [n = 41], PRCV/DEX [n = 41], mock/PBS [n = 23], and mock/DEX [n = 25]) were inoculated intranasally and intratracheally with the ISU-1 strain of PRCV (1 x 10(7) PFU) or cell culture medium. DEX was administered (once daily, 2 mg/kg of body weight/day, intramuscularly) from postinoculation day (PID) 1 to 6. In PRCV/DEX pigs, significantly milder pneumonia, fewer PRCV-positive cells, and lower viral RNA titers were present in lungs early at PID 2; however, at PID 4, 10, and 21, severe bronchointerstitial pneumonia, significantly higher numbers of PRCV-positive cells, and higher viral RNA titers were observed compared to results for PRCV/PBS pigs. Significantly lower numbers of CD2(+), CD3(+), CD4(+), and CD8(+) T cells were also observed in lungs of PRCV/DEX pigs than in those of PRCV/PBS pigs at PID 8 and 10, coincident with fewer gamma interferon (IFN-gamma)-secreting cells in the tracheobronchial lymph nodes as determined by enzyme-linked immunospot assay. Our results confirm that DEX treatment alleviates PRCV pneumonia early (PID 2) in the infection but continued use through PID 6 exacerbates later stages of infection (PID 4, 10, and 21), possibly by decreasing cellular immune responses in the lungs (IFN-gamma-secreting T cells), thereby creating an environment for more-extensive viral replication. These data have potential implications for corticosteroid use with SARS-CoV patients and suggest a precaution against prolonged use based on their unproven efficacy in humans, including possible detrimental secondary effects.


title: Brazilian recommendations of mechanical ventilation 2013. Part I.

text: Perspectives on invasive and noninvasive ventilatory support for critically ill patients are evolving, as much evidence indicates that ventilation may have positive effects on patient survival and the quality of the care provided in intensive care units in Brazil. For those reasons, the Brazilian Association of Intensive Care Medicine (Associação de Medicina Intensiva Brasileira - AMIB) and the Brazilian Thoracic Society (Sociedade Brasileira de Pneumologia e Tisiologia - SBPT), represented by the Mechanical Ventilation Committee and the Commission of Intensive Therapy, respectively, decided to review the literature and draft recommendations for mechanical ventilation with the goal of creating a document for bedside guidance as to the best practices on mechanical ventilation available to their members. The document was based on the available evidence regarding 29 subtopics selected as the most relevant for the subject of interest. The project was developed in several stages, during which the selected topics were distributed among experts recommended by both societies with recent publications on the subject of interest and/or significant teaching and research activity in the field of mechanical ventilation in Brazil. The experts were divided into pairs that were charged with performing a thorough review of the international literature on each topic. All the experts met at the Forum on Mechanical Ventilation, which was held at the headquarters of AMIB in São Paulo on August 3 and 4, 2013, to collaboratively draft the final text corresponding to each sub-topic, which was presented to, appraised, discussed and approved in a plenary session that included all 58 participants and aimed to create the final document.


title: [The application of a systematic-dynamic model to study the computer simulation of severe acute respiratory syndrome transmission and the impact of control measures].

text: OBJECTIVE (1) Building a macroscopical systematic-dynamic model of severe acute respiratory syndrome (SARS) transmission and disease control process. (2) To determine key variables on the control of SARS epidemic through computer simulation methodology, especially to analyze the effect of "screening for fever" practice during the epidemics. (3) To provide evidence for related decision-making. METHODS Parameters in the model were collected from local hospitals and municapal CDC through interview, questionnaire survey, literature review and case analysis. A systematic-dynamic model was built under similar studies. 'What-if' analysis was used during the simulation process. RESULTS (1) The mean duration between disease onset and hospital admission, rate of contacts of each infectious individual as well as the rate of contacts in hospital of each infectious individual appeared to be the key variables in the process of SARS transmission. (2) Physician's alertness/sense and practice of self-protection on SARS, measures on quarantine and isolation to the patients, ventilation and disinfection process in the wards appeared to be the key variables for the control of epidemics. (3) "Screening for fever" practice on each patient at the entrance of the hospital did not seem to act as an important factor to the control of the epidemics. CONCLUSION The health system in Beijing can control SARS epidemic rapidly based on current applied disease control measures and plan.


title: Closing the knowledge gaps on MERS: three and half years since its detection, what have we learnt and what needs to be done urgently? (Editorial).

text: The Middle East respiratory syndrome coronavirus (MERS-Cov), first detected in 2012, continues to cause health concerns owing to the grave uncertainties that have surrounded the virus since it emerged. Three and half years after the first known human infection was detected, cases continue to be reported every month, over 85% of which have been from Saudi Arabia and other countries in the Arabian Peninsula. Despite its low levels of transmission, the virus presents an uncertain future as a number of critical knowledge gaps on the source and route of transmission have hindered the global response to this emerging infection.


title: Identification and ultrastructural characterization of a novel virus from fish.

text: During routine investigations on fish, a virus (isolate DF 24/00) with novel morphological features and hitherto undescribed morphogenesis was isolated from a white bream (Blicca bjoerkna L.; Teleostei, order Cypriniformes). Cell-free virions consist of a rod-shaped nucleocapsid (120-150x19-22 nm) similar to that seen in baculoviruses. The virion has a bacilliform shape (170-200x75-88 nm) reminiscent of rhabdoviruses with an envelope containing coronavirus-like spikes (20-25 nm). DF 24/00 replicated well in various fish cell lines. Inhibitor studies with 5-iodo-2'-deoxyuridine indicated that the viral genome consists of RNA and chloroform sensitivity correlated with ultrastructural demonstration of enveloped virions. The buoyant density of the virus determined in sucrose was 1.17-1.19 g/ml. Preliminary biochemical characterization revealed the presence of six antigenic glycoproteins, three of which contain sugars with concanavalin-A specificity. Ultrastructurally, morphogenesis of virus progeny was detected only in the cytoplasm. Nucleocapsids were observed to bud through membranes of the endoplasmic reticulum and/or Golgi apparatus into dilated vesicles. Egress of mature virions occurs primarily by exocytosis and, only very rarely, by budding directly at the plasma membrane. Morphologically similar viruses had previously been isolated from grass carp (Ctenopharyngodon idella), blue crab (Callinectis sapidus), European shore crab (Carcinus maenas) and shrimp (Penaeus monodon). To date, none of them has been classified. In summary, the first characterization of a new virus that might represent a member of a novel virus family that has morphological features resembling those found in rhabdo-, corona- and baculoviruses is presented.


title: Blood cytokine, chemokine and gene expression in cholestasis patients with intractable pruritis treated with a molecular adsorbent recirculating system: a case series.

text: BACKGROUND The molecular adsorbent recirculating system (MARS) is an albumin-dialysis modality that has been investigated predominantly in patients with acute and acute-on-chronic liver failure. OBJECTIVES To report the clinical efficacy and safety of MARS therapy for intractable pruritus in cholestasis patients with stable chronic liver disease, characterizing the impact of MARS on cytokine levels and on the transcriptome in the blood compartment. METHODS MARS therapy was performed on three patients with cholestatic liver disease using 8 h runs for two consecutive days. The expression levels of 65 cytokines⁄chemokines and 24,000 genes were profiled by Luminex (Luminex Corporation, USA) and microarray, respectively. RESULTS A quality-of-life assessment demonstrated a marked improvement during therapy, which was sustained in two of three patients. No bleeding or infectious complications were observed. Bile acid levels were markedly reduced following MARS (mean [± SD] pretreatment 478.9±112.2 µmol⁄L versus post-treatment 89.7±68.8 µmol⁄L). Concordant decreases in cytokine⁄chemokine levels were noted for interleukin (IL)-1beta, IL-2, IL-6, IL-8, IL-12 (p40), RANTES, tranforming growth factor-alpha, tumour necrosis factor-alpha and thrombopoietin following MARS. On microarray profiling, biologically relevant concordant changes among all patients were evident for 20 different genes (10 upregulated and 10 downregulated). The upregulation of several potentially immune suppressive⁄regulatory genes (eg, early growth response 3 [EGR-3], ephrin-A2 [EFNA2] and serum amyloid A1 [SAA1]), concurrent with downregulation of genes involved in innate immunity (eg, toll-like receptor 4 interactor with leucine-rich repeats [TRIL]) and inflammation (eg, ephrin receptor B1 [EPHB1]), was observed. CONCLUSIONS This investigative approach offers new insights into intractable pruritus and suggests future therapeutic targets. The clinical benefit of MARS in cholestasis patients with intractable pruritus may not exclusively result from filtration of pruritogens, but also from systemic changes in cytokine⁄chemokine levels and changes in gene expression of blood cells.


title: Features of patients with 2019 novel coronavirus admitted in a pneumology department: The first retrospective Tunisian case series.

text: AIM On 2 March 2020, Tunisia has reported the first confirmed case of COVID-19. Since then, the disease has affected about 700 persons in the country. The purpose of our study was to report epidemiological, clinical, radiological and therapeutic features of patients with 2019-nCoV infection admitted in the pneumology department. METHODS We extracted the data of the consequetive 20 patients managed in the department of pneumology B at Abderrahmen Mami hospital, from March, 26 to April, 8, 2020. RESULTS The median age was 61 years old [41-85]. There were 9 men and 11 women. Underlying disorders were observed in 16 patients (80%). Five patients were health care workers. Three patients did not have any known exposure. Common symptoms included fever (100%), shortness of breath (70%) and cough (70%). Computed tomography scans showed bilateral ground glass opacities in 7/9 cases. Fifteen patients received both chloroquine and azithromycin. Fourteen patients (70%) were discharged before April, 8, 2020. Reported complications were: hypokalemia (3 cases), pulmonary embolism (2 cases) and QT prolongation (1 case). One patient died from acute cardiac injury. CONCLUSION Knowing the different aspects of moderate and severe forms of the disease can contribute to advance in infection control strategies.


title: NTP Toxicology and Carcinogenesis Studies of Benzyl Alcohol (CAS No. 100-51-6) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

text: Toxicology and carcinogenesis studies of technical-grade benzyl alcohol (99% pure), a textile dye additive, solvent, and food flavoring agent, were conducted by administering the chemical by gavage in corn oil vehicle to groups of F344/N rats and B6C3F1 mice of each sex for 16 days, 13 weeks, or 2 years. Short-Term Studies: In 16-day studies, all five male and five female rats and mice dosed with 2,000 mg/kg benzyl alcohol died. Two of five male and 3/5 female rats and 1/5 male and 2/5 female mice dosed with 1,000 mg/kg died. Rats and mice of each sex in the two highest dose groups were lethargic after dosing. Other toxic responses to benzyl alcohol in these dose groups included blood around the mouth and nose, subcutaneous hemorrhages, and blood in the urinary and gastrointestinal tracts of rats and blood in the urinary bladder of mice. Animals administered lower doses of benzyl alcohol (125, 250, or 500 mg/kg) had no compound-related histologic lesions. Doses selected for the 13-week studies were 0, 50, 100, 200, 400, and 800 mg/kg for rats and mice. Eight of 10 male rats dosed with 800 mg/kg died during weeks 7 and 8; four of these deaths were described as gavage related. Rats dosed with 800 mg/kg exhibited clinical signs indicative of neurotoxicity including staggering, respiratory difficulty, and lethargy. Hemorrhages occurred around the mouth and nose, and there were histologic lesions in the brain, thymus, skeletal muscle, and kidney. In mice, deaths were scattered among all dose levels, but none occurred in vehicle controls. Four male and six female mice died after being dosed; all deaths but one were described as gavage related. Staggering after dosing also occurred during the first 2 weeks of the studies in mice dosed with 800 mg/kg. Some of the deaths in the rats and mice may have been caused by a combination of the gavage procedure and chemical toxicity, since there was evidence that benzyl alcohol induced neurotoxic effects. There were reductions in relative weight gain in male rats dosed with 800 mg/kg benzyl alcohol, in female rats dosed with 200 mg/kg or more, in male mice dosed with 400 or 800 mg/kg, and in female mice dosed with 200 mg/kg or more. No notable changes in body weight gain or compound-related histopathologic lesions were observed in rats or mice from the lower dose groups. Based on mortality, reduction in relative body weight gain, and the histopathologic lesions, doses selected for 2-year studies in rats were 0, 200, and 400 mg/kg. Doses selected for 2-year studies in mice were 0, 100, and 200 mg/kg, based on mortality and depression in relative body weight gain. Body Weight and Survival in the Two-Year Studies: Fifty animals of each species and sex were administered benzyl alcohol in corn oil by gavage 5 days per week for 103 weeks. Administration of benzyl alcohol did not affect survival in male rats (final survival rates: vehicle control, 28/50; low dose, 27/50; high dose, 24/50) but reduced survival of dosed female rats by half (36/50; 18/50; 17/50). Many of the early deaths were considered related to the gavage procedure. Survival in mice was not affected by benzyl alcohol administration (male: 34/50; 33/50; 35/50; female: 26/50; 32/50; 36/50). No effect of benzyl alcohol on body weight gain in rats or mice was observed. In the third month of the studies, clinical signs of sialodacryoadenitis virus infection were observed in rats. A positive serologic reaction for rat coronavirus was observed in sentinel animals at 6 months and again at 18 months. Nonneoplastic and Neoplastic Effects in the Two-Year Studies: No apparent compound-related nonneoplastic responses were observed. Dose-related negative trends in the incidences of anterior pituitary gland neoplasms were seen in female rats (vehicle control, 29/50; low dose, 17/47; high dose, 9/49) and of harderian gland adenomas in male mice (8/50; 3/50; 2/50). Adenomas of the adrenal cortex occurred at an increased incidence in high dose male mice (0/48; 0/44; 3/48), but this slight increase was not considered to be related to chemical expcal exposure. Genetic Toxicology: Benzyl alcohol was not mutagenic when tested by the preincubational protocol in the presence or absence of exogenous metabolic activation in Salmonella typhimurium strains TA98, TA100, TA1535, or TA1537. In the mouse L5178Y/TK± lymphoma assay, benzyl alcohol induced an increase in trifluorothymidine (Tft)-resistant cells in the absence, but not in the presence, of S9; the effect was associated with toxicity. In cytogenetic assays with Chinese hamster ovary (CHO) cells, treatment with benzyl alcohol produced an increase in sister chromatid exchanges (SCEs) which was judged to be equivocal both with and without S9; a significant increase in chromosomal aberrations was observed after exposure to benzyl alcohol in the presence, but not the absence, of S9. Audit: The data, documents, and pathology materials from the 2-year studies of benzyl alcohol have been audited. The audit findings show that the conduct of the studies is documented adequately and support the data and results given in this Technical Report. Conclusions: Under the conditions of these 2-year gavage studies, there was no evidence of carcinogenic activity of benzyl alcohol for male or female F344/N rats dosed with 200 or 400 mg/kg. Survival in both dose groups of female rats was 50% that of vehicle controls, primarily due to an increased number of gavage-related deaths. There was no evidence of carcinogenic activity of benzyl alcohol for male or female B6C3F1 mice dosed with 100 or 200 mg/kg for 2 years. Synonyms: benzenemethanol; phenylcarbinol; phenylmethanol; a-hydroxytoluene; benzenecarbinol; phenolcarbinol; a-toluenol


title: Effect of severe acute respiratory syndrome on bystander willingness to perform cardiopulmonary resuscitation (CPR)--is compression-only preferred to standard CPR?

text: OBJECTIVE The effect of the severe acute respiratory syndrome (SARS) outbreak on the willingness of laypersons to provide bystander cardiopulmonary resuscitation (CPR) using standard CPR (SCPR) or compression-only CPR (CCPR) was evaluated. The preferred type of SCPR in the post-SARS era was assessed. METHODS A descriptive study was conducted through telephone interviews. Persons who attended a CPR course from January 2000 through February 2003 answered a structured questionnaire. The respondents' willingness to perform SCPR or CCPR during a witnessed cardiac arrest of an average adult stranger or that of a family member in the pre-SARS and the post-SARS era was surveyed. RESULTS Data for 305 respondents were processed. For the scenario of cardiac arrest of an average stranger, more respondents would perform CCPR than SCPR in the pre-SARS era (83.6% vs. 61.3%, p <0.001) and in the post-SARS era (77.4% vs. 28.9%, p <0.001). In the scenario of the cardiac arrest of a family member, more would perform CCPR than SCPR in the pre-SARS era (92.8% vs. 87.2%, p <0.001) and in the post-SARS era (92.8% vs. 84.9%, p <0.001). After SARS, more respondents were unwilling to perform SCPR (p <0.001) and CCPR (p <0.001) on strangers. After SARS, more respondents were unwilling to perform SCPR on a family member (p = 0.039), but there was no difference in the preference to perform CCPR (p = 1.000). CONCLUSIONS Concerns about SARS adversely affected the willingness of respondents to perform SCPR or CCPR on strangers and to perform SCPR on family members. Compression-only CPR was preferred to SCPR to resuscitate strangers experiencing cardiac arrest after the emergence of SARS.


Experts urge action to stop animal diseases infecting humans.


docid: taykbsbx

title: Rationale for Evaluating PDE4 Inhibition for Mitigating against Severe Inflammation in COVID-19 Pneumonia and Beyond.

text: BACKGROUND In the absence of definitive anti-viral therapy, there is considerable interest in mitigating against severe inflammatory reactions in coronavirus disease-2019 (COVID-19) pneumonia to improve survival. These reactions are sometimes termed cytokine storm. PDE4 inhibitors (PDE4i) have anti-inflammatory properties with approved indications in inflammatory skin and joint diseases as well as chronic obstructive pulmonary disease (COPD). Furthermore, multiple animal models demonstrate strong anti-inflammatory effects of PDE4i in respiratory models of viral and bacterial infection and also after chemically mediated lung injury. The rationale for PDE4i use in COVID-19 patients comes from the multimodal mechanism of action with cytokine, chemokine, and other key pathway inhibition all achieved with an excellent safety profile. We highlight how PDE4i could be an overlooked treatment from the rheumatologic and respiratory armamentarium, which has potential beneficial immune-modulation for treating severe COVID-19 pneumonia associated with cytokine storms. The proposed use of PDE4i is also supported by age-related immune changes in inflammation severity in PDE4i modifiable pathways in primate coronavirus disease. In conclusion, over-exuberant anti-viral immune responses in older patients with COVID-19 may pose a substantial risk to patient survival and mitigation against such hyper-inflammation with PDE4i, especially with anti-viral agents, is a strategy that need to be pursed, especially in older patients.


title: [Clinical characteristics and prognosis of 33 children with severe acute respiratory syndrome in Guangzhou area].

text: OBJECTIVE Since the outbreak of a highly contagious new pneumonia, atypical pneumonia or severe acute respiratory syndrome (SARS) occurred in Guangzhou area, 33 children with this syndrome were treated in the authors' hospital. The present study aimed to understand clinical characteristics and prognosis of pediatric SARS patients in Guangzhou area. METHODS Clinical manifestations, laboratory and radiologic findings, therapeutic approaches and prognosis of the 33 children with SARS in Guangzhou area were analyzed. RESULTS Of the 33 cases, 17 were males and 16 were females. The age was between 3 months to 13 years, and 3 - 12 years old patients accounted for 82%. Five (15%) cases had an evident history of contacting SARS patient before the symptoms occurred. Another 5 (15%) cases had a history that contacts of these patients (family members or friends) developed fever and/or cough later. The most common symptoms in this cohort were fever (100%) and cough (91%). Most of the cases had high fever, higher than 39 degrees C. Near half of the cases had nonproductive cough. The initial blood cells count showed that total white blood cell (WBC) count was (2.5 - 9.7) x 10(9)/L. In 22 (67%) cases the WBC count was < 5.0 x 10(9)/L, and in 10 (30%) WBC was (5.0 - 7.0) x 10(9)/L, in 18 cases most of the WBC were lymphocyte count. Chest radiograph showed patchy infiltrates, in 15 cases the changes were unilateral, and in 18 were bilateral. The radiologic changes developed fast, in some cases the changes progressed from one side to both sides. The opacity was absorbed slowly, significant absorption took in average two weeks. Elevated ALT was found in 3 cases and elevated CK-MB in 2 cases. Treatment included isolation, good ventilation of the ward, bed rest, supportive regimens, low volume oxygen inhalation, use of Chinese traditional medicine, antibiotics to prevent bacterial infection, and anti-inflammation therapy. All the patients recovered and discharged from hospital after a mean period of 10.0 +/- 3.8 days. CONCLUSION SARS in children may have its own characteristics. The main clinical manifestations were high fever and cough while no severe toxic symptoms, nor respiratory failure was seen; few symptoms or signs suggesting involvement of systems other than respiratory system were seen. Chest radiograph showed uni- or bilateral asymmetric air-space infiltrates which could worsen quickly and were absorbed slowly. Though there were severe changes in the lung, the patients might not have corresponding symptoms or signs. The total white blood cell count in peripheral blood did not increase. All the patients studied had a favorable outcome after the combined treatment.