title: Cell-based angiopoietin-1 gene therapy for acute lung injury.

text: RATIONALE The acute respiratory distress syndrome is a significant cause of morbidity and mortality in critically ill patients. Angiopoietin-1 (Ang-1), a ligand for the endothelial Tie2 receptor, is an endothelial survival and vascular stabilization factor that reduces endothelial permeability and inhibits leukocyte-endothelium interactions. OBJECTIVES We hypothesized that Ang-1 counteracts vascular inflammation and pulmonary vascular leak in experimental acute lung injury. METHODS We used cell-based gene therapy in a rat model of ALI. Transgenic mice overexpressing Ang-1 or deficient in the Tie2 receptor were also studied to better elucidate the mechanisms of protection. MEASUREMENTS AND MAIN RESULTS The present report provides data that support a strong protective role for the Ang-1/Tie2 system in two experimental models of LPS-induced acute lung injury. In a rat model, cell-based Ang-1 gene transfer improved morphological, biochemical, and molecular indices of lung injury and inflammation. These findings were confirmed in a gain-of-function conditional, targeted transgenic mouse model, in which Ang-1 reduced endothelial cell activation and the expression of adhesion molecules, associated with a marked improvement in airspace inflammation and intraalveolar septal thickening. Moreover, heterozygous Tie2-deficient mice demonstrated enhanced evidence of lung injury and increased early mortality. CONCLUSIONS These results support a critical role for the Ang-1/Tie2 axis in modulating the pulmonary vascular response to lung injury and suggest that Ang-1 therapy may represent a potential new strategy for the treatment and/or prevention of acute respiratory distress syndrome in critically ill patients.


Success and failure in human virus diseases. I. Aetiology.


title: ADP-ribose-1"-monophosphatase: a conserved coronavirus enzyme that is dispensable for viral replication in tissue culture.

text: Replication of the approximately 30-kb plus-strand RNA genome of coronaviruses and synthesis of an extensive set of subgenome-length RNAs are mediated by the replicase-transcriptase, a membrane-bound protein complex containing several cellular proteins and up to 16 viral nonstructural proteins (nsps) with multiple enzymatic activities, including protease, polymerase, helicase, methyltransferase, and RNase activities. To get further insight into the replicase gene-encoded functions, we characterized the coronavirus X domain, which is part of nsp3 and has been predicted to be an ADP-ribose-1"-monophosphate (Appr-1"-p) processing enzyme. Bacterially expressed forms of human coronavirus 229E (HCoV-229E) and severe acute respiratory syndrome-coronavirus X domains were shown to dephosphorylate Appr-1"-p, a side product of cellular tRNA splicing, to ADP-ribose in a highly specific manner. The enzyme had no detectable activity on several other nucleoside phosphates. Guided by the crystal structure of AF1521, an X domain homolog from Archaeoglobus fulgidus, potential active-site residues of the HCoV-229E X domain were targeted by site-directed mutagenesis. The data suggest that the HCoV-229E replicase polyprotein residues, Asn 1302, Asn 1305, His 1310, Gly 1312, and Gly 1313, are part of the enzyme's active site. Characterization of an Appr-1"-pase-deficient HCoV-229E mutant revealed no significant effects on viral RNA synthesis and virus titer, and no reversion to the wild-type sequence was observed when the mutant virus was passaged in cell culture. The apparent dispensability of the conserved X domain activity in vitro indicates that coronavirus replicase polyproteins have evolved to include nonessential functions. The biological significance of the novel enzymatic activity in vivo remains to be investigated.


title: Intracellular RNAs of the feline infectious peritonitis coronavirus strain 79-1146.

text: In Felis catus whole foetus D cells infected with feline infectious peritonitis virus (FIPV), strain 79-1146, six virus-specific, poly(A)-containing RNA species of about 20, 9.6, 5.2, 3.8, 2.8 and 1.6 kb were found. By translation in vitro the 3.8 and 2.8 kb RNAs were shown to encode the 25K envelope protein and the 45K nucleocapsid protein, respectively. The partial map of the FIPV genome was compared with genomic maps of porcine, murine and avian coronaviruses. Differences in these maps suggest that transcription units have been lost or gained during coronavirus divergence.


docid: qzibpvbr

title: Kawasaki disease.

text: PURPOSE OF REVIEW Kawasaki disease is still a dilemma for pediatricians, especially its atypical or incomplete presentation. The current diagnostic criteria appear inadequate, and the early diagnosis frequently remains challenging with high risk of coronary damage. This review focuses on recent data concerning Kawasaki disease etiology and pathogenesis, and emphasizes the proposal of including altered laboratory values in revised diagnostic criteria aimed at identifying patients with incomplete disease. RECENT FINDINGS Despite a timely treatment, approximately 15% of children have persistent or recurrent fever, thus requiring additional intravenous immunoglobulin, corticosteroids, immunosuppressant, and eventually biologic drugs. Recent cardiologic tests strongly suggest that endothelial damage may lead to coronary stenosis and myocardial ischemia over time, even in children apparently normal at initial cardiac evaluation. New noninvasive tools are suggested to monitor coronary artery aneurysm outcome. Giant coronary artery aneurysms still represent a severe life-threatening complication. There is as yet no agreement regarding the prevention of thrombosis and stenosis in children with giant aneurysms. SUMMARY Due to earlier recognition, aggressive medical treatment, and surgical procedures, the quality of life in patients with Kawasaki disease is significantly improved. The identification of children at high risk for coronary artery aneurysms is crucial in order to reduce the occurrence of sudden death in adolescence and early adulthood. High parameters of inflammation, anemia, and low sodium and albumin levels, along with persistent unexplained fever, should alert clinicians to suspect the disease even though all clinical symptoms are lacking.


title: The State Laboratory of Hygiene's role in terrorism preparedness and response.

text: In the fall of 2001, the national public health system found itself responding to acts of terrorism. The intentional release of Bacillus anthracis spores on the East Coast tested the capacity of all state public health laboratories to respond. The impact on the public health system extended to the Wisconsin State Laboratory of Hygiene (WSLH). Fortunately, participation in the National Laboratory Response Network helped the WSLH meet the challenge of 24 hour/7 days a week coverage, and subsequent federal funding increases have enabled the WSLH to expand its technical capabilities and provide training and outreach to other Wisconsin laboratories to prepare them for their roles in man-made or naturally-occurring public health emergencies.


title: Pathogenesis of coronavirus-induced infections. Review of pathological and immunological aspects.

text: Coronaviruses and arteriviruses infect multiple species of mammals, including humans, causing diseases that range from encephalitis to enteritis. Several of these viruses infect domestic animals and cause significant morbidity and mortality, leading to major economic losses. In this category are included such pathogens as transmissible gastroenteritis virus, porcine respiratory and reproductive virus and infectious bronchitis virus. The feline coronaviruses (FECV) generally do not cause infections with high morbidity but in a small percentage of cases, the virus mutates to become more virulent. This virus, feline infectious peritonitis virus (FIPV), causes severe disease in young cats. This disease is in large part immunopathological and understanding it is a major goal of coronavirus research.


Dispatches from the front line.


title: Viruses associated with outbreaks of equine respiratory disease in New Zealand.

text: AIM To identify viruses associated with respiratory disease in young horses in New Zealand. METHODS Nasal swabs and blood samples were collected from 45 foals or horses from five separate outbreaks of respiratory disease that occurred in New Zealand in 1996, and from 37 yearlings at the time of the annual yearling sales in January that same year. Virus isolation from nasal swabs and peripheral blood leukocytes (PBL) was undertaken and serum samples were tested for antibodies against equine herpesviruses (EHV-1, EHV-2, EHV-4 and EHV-5), equine rhinitis-A virus (ERAV), equine rhinitis-B virus (ERBV), equine adenovirus 1 (EAdV-1), equine arteritis virus (EAV), reovirus 3 and parainfluenza virus type 3 (PIV3). RESULTS Viruses were isolated from 24/94 (26%) nasal swab samples and from 77/80 (96%) PBL samples collected from both healthy horses and horses showing clinical signs of respiratory disease. All isolates were identified as EHV-2, EHV-4, EHV-5 or untyped EHV. Of the horses and foals tested, 59/82 (72%) were positive for EHV-1 and/or EHV-4 serum neutralising (SN) antibody on at least one sampling occasion, 52/82 (63%) for EHV-1-specific antibody tested by enzyme-linked immunosorbent assay (ELISA), 10/80 (13%) for ERAV SN antibody, 60/80 (75%) for ERBV SN antibody, and 42/80 (53%) for haemagglutination inhibition (HI) antibody to EAdV-1. None of the 64 serum samples tested were positive for antibodies to EAV, reovirus 3 or PIV3. Evidence of infection with all viruses tested was detected in both healthy horses and in horses showing clinical signs of respiratory disease. Recent EHV-2 infection was associated with the development of signs of respiratory disease among yearlings [relative risk (RR)=2.67, 95% CI=1.59-4.47, p=0.017]. CONCLUSIONS Of the equine respiratory viruses detected in horses in New Zealand during this study, EHV-2 was most likely to be associated with respiratory disease. However, factors other than viral infection are probably important in the development of clinical signs of disease.


title: Advantages of minimal incision laparoscopic cholecystectomy.

text: BACKGROUND Modifications to conventional laparoscopic cholecystectomy (CLC) are aimed at decreasing abdominal wall trauma and improving cosmetic outcome. Although single-incision laparoscopic surgery (SILS) provides excellent cosmetic results, the procedure is technically challenging and expensive compared to the conventional laparoscopic approach. OBJECTIVES To describe a novel, hybrid technique combining SILS and conventional laparoscopy using minimal abdominal wall incisions. METHODS Fifty patients diagnosed with symptomatic cholelithiasis were operated using two reusable 5 mm trocars inserted through a single 15 mm umbilical incision and a single 2-3 mm epigastric port. This technique was clubbed "minimal incision laparoscopic cholecystectomy" (MILC). RESULTS MILC was completed in 49 patients (98%). In five patients an additional 3 mm trocar was used and in 2 patients the epigastric trocar was switched to a 5 mmtrocar. The procedure was converted to CLC in one patient. Mean operative time was 29 minutes (range 18-60) and the average postoperative hospital stay was 22 hours (range 6-50). There were no postoperative complications and the cosmetic results were rated excellent by the patients. CONCLUSIONS MILC is an intuitive, easy-to-learn and reproducible technique and requires small changes from CLC. As such, MILC may be an attractive alternative, avoiding the cost and complexity drawbacks associated with SILS.


title: The challenges of "continuing medical education" in a pandemic era.

text: Closure of medical schools or the barring of "live patient" contact during an epidemic or pandemic is potentially disruptive to medical education. During the SARS epidemic, the use of web-based learning, role play, video vignettes and both live and mannequin-based simulated patients minimised disruptions to medical education. This article examines the pedagogical innovations that allow clinical teaching to continue without medical students examining actual patients, and proposes a contingency plan in the event of future outbreaks that may necessitate similar containment measures.


title: Single amino acid substitutions in the severe acute respiratory syndrome coronavirus spike glycoprotein determine viral entry and immunogenicity of a major neutralizing domain.

text: Neutralizing antibodies (NAbs) against severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) spike (S) glycoprotein confer protection to animals experimentally infected with the pathogenic virus. We and others previously demonstrated that a major mechanism for neutralizing SARS-CoV was through blocking the interaction between the S glycoprotein and the cellular receptor angiotensin-converting enzyme 2 (ACE2). In this study, we used in vivo electroporation DNA immunization and a pseudovirus-based assay to functionally evaluate immunogenicity and viral entry. We characterized the neutralization and viral entry determinants within the ACE2-binding domain of the S glycoprotein. The deletion of a positively charged region Sdelta(422-463) abolished the capacity of the S glycoprotein to induce NAbs in mice vaccinated by in vivo DNA electroporation. Moreover, the Sdelta(422-463) pseudovirus was unable to infect HEK293T-ACE2 cells. To determine the specific residues that contribute to related phenotypes, we replaced eight basic amino acids with alanine. We found that a single amino acid substitution (R441A) in the full-length S DNA vaccine failed to induce NAbs and abolished viral entry when pseudoviruses were generated. However, another substitution (R453A) abolished viral entry while retaining the capacity for inducing NAbs. The difference between R441A and R453A suggests that the determinants for immunogenicity and viral entry may not be identical. Our findings provide direct evidence that these basic residues are essential for immunogenicity of the major neutralizing domain and for viral entry. Our data have implications for the rational design of vaccine and antiviral agents as well as for understanding viral tropism.


title: Targeting of active sialyltransferase to the plant Golgi apparatus.

text: Glycosyltransferases in the Golgi apparatus synthesize cell wall polysaccharides and elaborate the complex glycans of glycoproteins. To investigate the targeting of this type of enzyme to plant Golgi compartments, we generated transgenic Arabidopsis plants expressing alpha-2,6-sialyltransferase, a glycosyltransferase of the mammalian trans-Golgi cisternae and the trans-Golgi network. Biochemical analysis as well as immunolight and immunoelectron microscopy of these plants indicate that the protein is targeted specifically to the Golgi apparatus. Moreover, the protein is predominantly localized to the cisternae and membranes of the trans side of the organelle. When supplied with the appropriate substrates, the enzyme has significant alpha-2,6-sialyltransferase activity. These results indicate a conservation of glycosyltransferase targeting mechanisms between plant and mammalian cells and also demonstrate that glycosyltransferases can be subcompartmentalized to specific cisternae of the plant Golgi apparatus.


Colorectal surgery--the Cinderella specialty.


Respiratory tract infection.


docid: sdtiyrab

title: Global efforts on vaccines for COVID-19: Since, sooner or later, we all will catch the coronavirus.

text: COVID-19 is an emerging infectious disease that has turned into a pandemic. It spreads through droplet transmission of the new coronavirus SARS-CoV-2. It is an RNA virus displaying a spike protein as the major surface protein with significant sequence similarity to SARS-CoV which causes severe acute respiratory syndrome. The receptor binding domain of the spike protein interacts with the human angiotensin converting enzyme 2 and is considered as the antigenic determinant for stimulating an immune response. While multiple candidate vaccines are currently under different stages of development, there are no known therapeutic interventions at the moment. This review describes the key genetic features that are being considered for generating vaccine candidates by employing innovative technologies. It also highlights the global efforts being undertaken to deliver vaccines for COVID-19 through unprecedented international cooperation and future challenges post development.


title: SARS/avian coronaviruses.

text: In the hunt for the aetiology of the SARS outbreak in 2003, a newly developed virus DNA micro-array was successfully used to hybridise PCR products obtained by random amplification of nucleic acids extracted from a cell culture infected with material from a SARS patient. The SARS agent was found to hybridise with micro-array probes from both coronaviruses and astroviruses, but one of the coronavirus probes and the four astrovirus probes contained redundant sequences, spanning a highly conserved motif, named s2m, found at the 3' end of the genomes of almost all astroviruses, one picornavirus, and the poultry coronaviruses. The three other coronavirus probes, that hybridised with the SARS agent, were located in the replicase gene, and it could be concluded that the SARS agent was a novel coronavirus, harbouring s2m. The presence of this motif in different virus families is probably the result of recombinations between unrelated viruses, but its presence in both poultry and SARS coronaviruses could suggest a bird involvement in the history of the SARS coronavirus. A recent screening of wild birds for the presence of coronaviruses, using a pan-coronavirus RT-PCR, led to the identification of novel coronaviruses in the three species studied. Phylogenetic analyses performed on both replicase gene and nucleocapsid protein could not add support to a close relationship between avian and SARS coronaviruses, but all the novel avian coronaviruses were found to harbour s2m. The motif is inserted at a homologous place in avian and SARS coronavirus genomes, but in a somewhat different context for the SARS coronavirus. If the presence of s2m in these viruses is a result of two separate recombination events, this suggests that its particular position in these genomes is the only one that would not be deleterious for coronaviral replication, or that it is the result of a copy-choice recombination between coronaviruses, following an ancestral introduction in the coronavirus family by an unrelated virus. In conclusion, the relative high frequencies of recombination observed both experimentally and in the natural evolution of RNA viruses, indicate that horizontal gene transfer does occur, even between unrelated viruses. This might represent a challenge in the rapid identification of novel pathogens with DNA micro-array techniques.


title: Presentation of severe acute respiratory syndrome (SARS) patients in a screening centre.

text: INTRODUCTION On 22 March 2003, the Ministry of Health, Singapore, designated Tan Tock Seng Hospital as the nationwide severe acute respiratory syndrome (SARS) hospital and its Emergency Department (ED) took over the role as the screening center for SARS on 26 March 2003. We describe the initial clinical characteristics of probable or suspect SARS patients that presented to the ED. METHODS A retrospective study of patients who were admitted through the ED and subsequently diagnosed to have probable SARS and suspect SARS was done. The data of these patients from the ED log were reviewed and analysed. RESULTS From 13 March 2003 to 31 May 2003, 11,461 patients were screened for SARS and 1,386 patients were admitted. Of these, 117 patients were diagnosed to have probable SARS and 146 suspect SARS. Their mean age was 36.7 years (range 1-80). Among these patients, there were 122 men (46.4 percent), and 205 were Singaporeans (77.9 percent). 13 patients had no initial contact history upon presentation to the ED. The mean duration between onset of symptom to presentation to the ED was 3.1 days. Travel history was less common in probable SARS cases than in suspect SARS cases as the epidemic was due mainly to local transmission. Fever was the most common presenting symptom (91.6 percent), and gastrointestinal symptoms were the least (6.9 percent). In the ED, 249 (94.7 percent) patients had chest radiographs and 86 (32.7 percent) had full blood count done. 22.2 percent of probable SARS patients had normal chest radiographs when they first presented to the ED. CONCLUSION The World Health Organisation criteria were important screening tools and admission guides, but should not be strictly followed. It was difficult to differentiate between probable and suspect SARS patients in the ED.


title: Effects of experimental Mycoplasma pulmonis infection on sensory neuropeptides and airway mucosa in the rat.

text: The effect of airway infection on neurogenic inflammation is not known. The present study examines the effect of Mycoplasma pulmonis infection on the sensory neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) in the trigeminal ganglion and in the mucosa of the nose and trachea in rats. We compared germ-free (GF), conventionally raised (CV) and specific pathogen-free (SPF) rats. The concentrations of SP and CGRP in the nasal mucosa were assessed with immunohistochemistry, and their prohormonal transcripts in the trigeminal ganglion were assessed with Northern blot. Mucosa was also processed for light microscopy and electron microscopy. SP-like immunoreactivity was greater in the nasal mucosa of infected animals than in uninfected controls. CGRP-like immunoreactivity was greater in the nasal septum, but not in the nasal turbinate, of infected than uninfected animals. In contrast, no change was evident in the expression levels of the prohormonal transcripts in the trigeminal ganglion. Infected nasal and tracheal mucosa was oedematous and locally infiltrated with inflammatory cells. In the nose of uninfected GF rats, subepithelial lymphoid aggregations were scarce and appeared inactive. We conclude that Mycoplasma pulmonis infection results in increased immunoreactivity of substance P, probably within nerves. There was no clear evidence of increased synthesis of the precursors of substance P and calcitonin gene-related peptide.


docid: ptbuuowf

title: Progress in hepatitis B prevention through universal infant vaccination--China, 1997-2006.

text: Hepatitis B virus (HBV) infection is a leading cause of illness and death in China. Approximately 60% of the population has a history of HBV infection, and 9.8% of persons in China are chronically infected with HBV and at risk for premature death from liver disease. Each year, an estimated 263,000 persons in China die from HBV-related liver cancer or cirrhosis, accounting for 37%-50% of HBV-related deaths worldwide. Because most HBV infections occur during infancy or early childhood, when HBV infection is most likely to become chronic, vaccination of infants beginning at birth is the key strategy for preventing chronic HBV infection. This report describes China's progress in increasing coverage among infants with hepatitis B vaccine (HepB) and timely administration of the HepB birth dose (i.e., within 24 hours of birth). Infant vaccination coverage with both the timely birth dose and the complete vaccine series was substantially higher among children born during 2003 than among those born during 1997; timely birth-dose coverage increased from 29.1% to 75.8%, and HepB series completion increased from 70.7% to 89.8%. Furthermore, in economically disadvantaged populations in western and middle provinces targeted by the China-Global Alliance for Vaccines and Immunization (China-GAVI) project, reported coverage with timely HepB birth dose increased from 64% in 2004 to 81% in 2006, and coverage with the complete HepB series increased from 52% in 2001 to 92% in 2006. China has established a goal to reduce chronic HBV infection among children aged <5 years to <1% by 2010. Achieving this goal will require continued commitment to increasing vaccination coverage in impoverished regions and ensuring that infants born at home are vaccinated within 24 hours of birth.


docid: hmhrtubb

title: Methicillin-resistant Staphylococcus aureus toxic shock syndrome.


title: Infectious disease survey of Rio Grande wild turkeys in the Edwards Plateau of Texas.

text: State wildlife agencies have translocated thousands of wild turkeys (Meleagris gallopavo) since the 1930s to reestablish this species. Because of threats to the domestic poultry industry and wild birds, screening for selected infectious agents has become routine since the early 1980s. One of the principal sources for Rio Grande wild turkeys (M. gallopavo intermedia) for translocation purposes was the Edwards Plateau of Texas (USA). Unfortunately, turkey abundance has declined in the southern Edwards Plateau since the late 1970s. Surprisingly few studies have addressed wild turkeys in this region, perhaps reflecting its status as the heart of Rio Grande turkey range. We surveyed 70 free-living Rio Grande wild turkeys from Bandera and Kerr counties, Texas, for evidence of exposure to Salmonella typhimurium, S. pullorum, Mycoplasma gallisepticum, M. meleagridis, M. synoviae, Chlamydophila psittaci, and the avian influenza, Newcastle disease, turkey corona, and reticuloendotheliosis viruses. Of these, 80% (56) were seropositive for both M. gallisepticum and M. synoviae on the serum plate antigen test. Ten of these individuals (14% of total) were positive for M. synoviae by hemagglutination inhibition testing. All other serologic tests were negative. Two adult females sampled in Kerr County, whose body mass was significantly less than that of other adult females trapped in the area, tested positive for reticuloendotheliosis virus (REV) proviral DNA on polymerase chain reaction. Reticuloendotheliosis virus was isolated from one of these individuals. The pathogenesis, transmission, and/or population-level influences of M. gallisepticum, M. synoviae, and REV in Rio Grande wild turkeys deserves further study.


title: [Vaccines, biotechnology and their connection with induced abortion].

text: Diploid cells (WI-38, MRC-5) vaccines have their origin in induced abortions. Among these vaccines we fi nd the following: rubella, measles, mumps, rabies, polio, smallpox, hepatitis A, chickenpox, and herpes zoster. Nowadays, other abortion tainted vaccines cultivated on transformed cells (293, PER.C6) are in the pipeline: flu, Respiratory Syncytial and parainfluenza viruses, HIV, West Nile virus, Ebola, Marburg and Lassa, hepatitis B and C, foot and mouth disease, Japanese encephalitis, dengue, tuberculosis, anthrax, plague, tetanus and malaria. The same method is used for the production of monoclonal antibodies and other proteins, gene therapy and genomics. Technology enables us to develop the aforementioned products without resorting to induced abortion. Full disclosure of the cell origin in the labelling of vaccines and other products must be supported. There are vaccines from non-objectionable sources which should be made available to the public. When no alternative vaccines exist, ethical research must be promoted. Non-objectionable sources in the production of monoclonal antibodies, gene therapy and genomics must be encouraged. It is not be consistent to abstain from products originated in embryonic stem cells and at the same time approve of products obtained from induced abortions. It is of paramount importance to avoid that induced abortion technology seeps into every field of Medicine.


title: Recombinant dimeric small immunoproteins neutralize transmissible gastroenteritis virus infectivity efficiently in vitro and confer passive immunity in vivo.

text: Small immunoproteins (SIPs) are single-chain molecules comprising the variable regions of an antibody assembled in a single polypeptide (scFv) and joined to the immunoglobulin heavy-chain dimerizing domain. To investigate the potential of these molecules to provide protection against enteric infections when supplied orally, SIPs were generated against Transmissible gastroenteritis virus (TGEV), a highly pathogenic porcine virus. Different variants of TGEV-specific SIPs were created, of epsilon and alpha isotypes, by exploiting the dimerizing domains epsilonCH4 and alphaCH3 of human and swine origin. Transfected cells secreted these recombinant mini-antibodies efficiently, mainly as dimers stabilized covalently by inter-chain disulphide bridges. The specificity and functionality of the recombinant TGEV-specific SIPs were determined by in vitro binding, neutralization and infection-interference assays. The neutralization indices of the TGEV-specific SIPs were all very similar to that of the original TGEV-specific mAb, thus confirming that the immunological properties have been preserved in the recombinant SIPs. In vivo protection experiments on newborn piglets have, in addition, demonstrated a strong reduction of virus titre in infected tissues of animals treated orally with TGEV-specific SIPs. It has therefore been demonstrated that it is possible to confer passive immunization to newborn pigs by feeding them with recombinant SIPs.


Detection of rodent RNA viruses by polymerase chain reaction.


Pathogenic characteristics of neutralization-resistant variants of JHM coronavirus (MHV-4).


title: Role of ventilation in airborne transmission of infectious agents in the built environment - a multidisciplinary systematic review.

text: There have been few recent studies demonstrating a definitive association between the transmission of airborne infections and the ventilation of buildings. The severe acute respiratory syndrome (SARS) epidemic in 2003 and current concerns about the risk of an avian influenza (H5N1) pandemic, have made a review of this area timely. We searched the major literature databases between 1960 and 2005, and then screened titles and abstracts, and finally selected 40 original studies based on a set of criteria. We established a review panel comprising medical and engineering experts in the fields of microbiology, medicine, epidemiology, indoor air quality, building ventilation, etc. Most panel members had experience with research into the 2003 SARS epidemic. The panel systematically assessed 40 original studies through both individual assessment and a 2-day face-to-face consensus meeting. Ten of 40 studies reviewed were considered to be conclusive with regard to the association between building ventilation and the transmission of airborne infection. There is strong and sufficient evidence to demonstrate the association between ventilation, air movements in buildings and the transmission/spread of infectious diseases such as measles, tuberculosis, chickenpox, influenza, smallpox and SARS. There is insufficient data to specify and quantify the minimum ventilation requirements in hospitals, schools, offices, homes and isolation rooms in relation to spread of infectious diseases via the airborne route. PRACTICAL IMPLICATION: The strong and sufficient evidence of the association between ventilation, the control of airflow direction in buildings, and the transmission and spread of infectious diseases supports the use of negatively pressurized isolation rooms for patients with these diseases in hospitals, in addition to the use of other engineering control methods. However, the lack of sufficient data on the specification and quantification of the minimum ventilation requirements in hospitals, schools and offices in relation to the spread of airborne infectious diseases, suggest the existence of a knowledge gap. Our study reveals a strong need for a multidisciplinary study in investigating disease outbreaks, and the impact of indoor air environments on the spread of airborne infectious diseases.


title: Translation but not the encoded sequence is essential for the efficient propagation of the defective interfering RNAs of the coronavirus mouse hepatitis virus.

text: The defective interfering (DI) RNA MIDI of mouse hepatitis virus strain A59 (MHV-A59) contains a large open reading frame (ORF) spanning almost its entire genome. This ORF consists of sequences derived from ORF1a, ORF1b, and the nucleocapsid gene. We have previously demonstrated that mutations that disrupt the ORF decrease the fitness of MIDI and its derivatives (R. J. de Groot, R. G. van der Most, and W. J. M. Spaan, J. Virol. 66:5898-5905, 1992). To determine whether translation of the ORF per se is required or whether the encoded polypeptide or a specific sequence is involved, we analyzed sets of related DI RNAs containing different ORFs. After partial deletion of ORF1b and nucleocapsid gene sequences, disruption of the remaining ORF is still lethal; translation of the entire ORF is not essential, however. When a large fragment of the MHV-A59 spike gene, which is not present in any of the MHV-A59 DI RNAs identified so far, was inserted in-frame into a MIDI derivative, translation across this sequence was vital to DI RNA survival. Thus, the translated sequence is irrelevant, indicating that translation per se plays a crucial role in DI virus propagation. Next, it was examined during which step of the viral life cycle translation plays its role. Since the requirement for translation also exists in DI RNA-transfected and MHV-infected cells, it follows that either the synthesis or degradation of DI RNAs is affected by translation.


title: Surrogate viruses for testing virucidal efficacy of chemical disinfectants

text: Abstract Since important agents of viral nosocomial infections like hepatitis B and C viruses and norovirus do not replicate sufficiently in cell culture systems, disinfectants with suspected efficacy against these viruses must be evaluated by different methods. Besides molecular approaches and indirect tests, the use of surrogate viruses with similar biophysical properties and genomic structure allows the assessment of virucidal efficacy of chemical disinfectants in quantitative suspension tests. Furthermore, insights into the survival of these viruses in the environment are possible. In recent years, duck hepatitis B virus and bovine viral diarrhoea virus have been tested as surrogates for hepatitis B and C viruses. Feline calicivirus serves as a surrogate for the group of norovirus. By including these viruses in inactivation experiments, valuable data from suspension tests can be derived on the virucidal efficacy of chemical disinfectants. Even in vivo tests using fingerpads of adult volunteers can be performed with these animal viruses without risk of infection. In contrast to in vitro examinations, the results of these tests allow use recommendations of chemical disinfectants for outbreak situations and daily routine disinfection.


title: Emergency response vaccines: lessons learned in response to communicable diseases.

text: In response to recent political and epidemiological events, the availability of emergency response vaccines has received high priority on the global agenda. An emergency response vaccine is defined as a vaccine of public health importance that should be available to all people at risk against epidemic, pandemic or global threat situations. This review focuses on global threat vaccines, those that would be used in the case of an emerging pathogen or the intentional release of an agent to which there is a low level of population immunity. The development and use of such vaccines requires attention to simultaneous actions on seven fronts: development, forecasting, supply sources, regulation, procurement, financing and allocation. Neglect of any one of these aspects will threaten the success of the project. A case study on smallpox vaccines illustrates this. Although many public health experts fear that attention to stockpiling emergency response vaccines could draw resources from other areas, some aspects of such an effort could positively impact the supply of other needed vaccines.


title: Transmission of vancomycin-resistant enterococcus in a neonatal intensive care unit.

text: An outbreak of vancomycin-resistant Enterococcus transmission in our neonatal intensive care unit persisted despite strict contact precautions and cohorting of colonized neonates and their caregivers. After terminal cleaning was performed, incubators were found to harbor the neonates' clone of vancomycin-resistant Enterococcus. Transmission ceased after cohorting of incubators, suggesting the effectiveness of infection control measures targeting environmental contamination.


title: Preliminary report on the observation of a coronavirus in the intestine of the laboratory rabbit.

text: Intestinal infections are a major cause of mortality in domestic rabbits. Although a few pathogenic organisms have been associated with this type of infection, it is often impossible to demonstrate the presence of any etiologic agents. Recently viral particles were observed in the intestine of diseased rabbits submitted to our laboratory for diagnosis. A study was then initiated to evaluate the presence of viral agents in the intestine of rabbits showing clinical signs of enteritis. Viral particles with morphological characteristics of the Coronaviridae family were observed by electron microscopy in most specimens of fecal material obtained from sick rabbits. Such particles were not seen in the feces of healthy animals. These particles, which have a density of 1.07-1.18g/cm3 on sucrose gradient, hemagglutinate rabbit red blood cells. Furthermore this virus has some antigenic relationship with the human coronavirus 229-E since immune serum to this virus blocks the hemagglutination of the rabbit erythrocytes. Antibody titers to this virus were detected in rabbit sera obtained from colonies with a high incidence of intestinal infections. When fecal material containing coronavirus particles were inoculated on various tissue culture systems, no cytopathic effects were observed.


title: The pandemic influenza policy model: a planning tool for military public health officials.

text: The Pandemic Influenza Policy Model (PIPM) is a collaborative computer modeling effort between the U.S. Department of Defense (DoD) and the Johns Hopkins University Applied Physics Laboratory. Many helpful computer simulations exist for examining the propagation of pandemic influenza in civilian populations. We believe the mission-oriented nature and structured social composition of military installations may result in pandemic influenza intervention strategies that differ from those recommended for civilian populations. Intervention strategies may differ between military bases because of differences in mission, location, or composition of the population at risk. The PIPM is a web-accessible, user-configurable, installation-specific disease model allowing military planners to evaluate various intervention strategies. Innovations in the PIPM include expanding on the mathematics of prior stochastic models, using military-specific social network epidemiology, utilization of DoD personnel databases to more accurately characterize the population at risk, and the incorporation of possible interventions, e.g., pneumococcal vaccine, not examined in previous models.


docid: hvkwlgbk

title: Changes in human nasal mucosa during experimental coronavirus common colds.

text: Twenty-four adult volunteers were inoculated with nasal drops containing a coronavirus of 229E serotype to determine the differences in the clinical and physiological reactions which occur between clinically infected, sub-clinically infected and non-infected individuals. Thirteen volunteers were clinically infected, 8 had sub-clinical infections and 3 were uninfected. Nasal airway resistance and the temperature of the nasal mucosa increased in all infected subjects both with and without symptoms: the core temperature increased also but to a lesser extent. Mucosal blood flow and nasal secretion increased only in those with symptoms. The albumin content of the nasal secretion increased in the clinically infected, suggesting that it was derived, partially at least, from the circulation. The nasal cycle of variation in airway resistance between the two sides of the nose was observed in all three groups but increased only in those clinically infected.


title: Fixed obstructive lung disease among workers in the flavor-manufacturing industry--California, 2004-2007.

text: Bronchiolitis obliterans, a rare and life-threatening form of fixed obstructive lung disease, is known to be caused by exposure to noxious gases in occupational settings and has been described in workers in the microwave-popcorn industry who were exposed to artificial butter-flavoring chemicals, including diacetyl. In August 2004, the California Department of Health Services (CDHS) and Division of Occupational Safety and Health (Cal/OSHA) received the first report of a bronchiolitis obliterans diagnosis in a flavor-manufacturing worker in California. In April 2006, a second report was received of a case in a flavor-manufacturing worker from another company. Neither worker was employed in the microwave-popcorn industry; both were workers in the flavor-manufacturing industry, which produces artificial butter flavoring and other flavors such as cherry, almond, praline, jalapeno, and orange. Both workers had handled pure diacetyl, an ingredient in artificial butter and other flavorings, and additional chemicals involved in the manufacturing process. Studies have indicated that exposure to diacetyl causes severe respiratory epithelial injury in animals. Because the manufacture of flavorings involves more than 2,000 chemicals, workers in the general flavor-manufacturing industry are exposed to more chemicals than workers in the microwave-popcorn industry, which primarily uses butter flavorings. Food flavorings are designated "generally recognized as safe" when approved by the U.S. Food and Drug Administration; flavorings are not known to put consumers at risk for lung disease. This report describes the first two cases of bronchiolitis obliterans in flavor-manufacturing workers in California, the findings of the public health investigation, and the actions taken by state and federal agencies to prevent future cases of occupational bronchiolitis obliterans. To identify cases and reduce risk for lung disease from occupational exposure to flavorings, a timely, effective response is needed, including medical surveillance, exposure monitoring, and reduced exposure.


Desmopressin before liver transplantation.


title: A Bayesian dynamic model for influenza surveillance.

text: The severe acute respiratory syndrome (SARS) epidemic, the growing fear of an influenza pandemic and the recent shortage of flu vaccine highlight the need for surveillance systems able to provide early, quantitative predictions of epidemic events. We use dynamic Bayesian networks to discover the interplay among four data sources that are monitored for influenza surveillance. By integrating these different data sources into a dynamic model, we identify in children and infants presenting to the pediatric emergency department with respiratory syndromes an early indicator of impending influenza morbidity and mortality. Our findings show the importance of modelling the complex dynamics of data collected for influenza surveillance, and suggest that dynamic Bayesian networks could be suitable modelling tools for developing epidemic surveillance systems.


title: [Experience of application of nonsuture electrowelding technologies in thoracic surgery].

text: Experience of application of nonsuture electrowelding technologies (NEWT) was analyzed while performing open and miniinvasive thoracoscopic operations in 116 patients. No essential differences were revealed while comparing domestic and foreign electrowelding surgical instruments. Possibility of wide application of NEWT in miniinvasive videothoracoscopic surgery was demonstrated.


Safety of herbal medicines in children.


title: Western equine encephalitis mimicking herpes simplex encephalitis.

text: A patient with severe encephalitis had focal findings suggesting herpes simplex encephalitis. After brain biopsy and administration of vidarabine, the patient's condition improved but was ultimately diagnosed as a case of western equine encephalitis. Further complicating laboratory diagnosis, an endogenous murine coronavirus was isolated from newborn mice inoculated with the patient's brain biopsy tissue. This case illustrates the need for caution in attributing therapeutic responses to antiviral agents or in attributing human illness to viruses that are actually endogenous to animals and tissue culture used in diagnostic virology.


title: Prospective randomized trial of mesh fixation with absorbable versus nonabsorbable tacker in laparoscopic ventral incisional hernia repair.

text: The aim of this prospective randomized trial was to compare 2 main fixation devices in regard to pain and recurrence in laparoscopic ventral incisional hernia repair (LVIHR). A total of 51 patients were evaluated in this study (n = 25, nonabsorbable tack (NAT) and n = 26, absorbable tack (AT) groups). A visual analogue scale (VAS) was performed on both groups preoperatively and on the postoperative (PO) first day, second week, and sixth month. All patients were followed for recurrence by clinical examination, ultrasonography, and/or abdominal computed tomography. The median follow-up time was 31 months (15-45). The mean age and the mean body mass index (BMI) of the patients were 53.1 ± 11 years and 34 ± 5 kg/m(2), respectively. The median defect size was 60 cm(2) (35-150) and median operation time was 110 minutes (40-360). In 2 patients from AT group and 2 from NAT group (7.8%), recurrence occurred. The 2 groups had similar features regarding demographics, operation time, postoperative hospital stay, morbidity, and VAS scores. The 2 fixation methods were found similar for PO pain and recurrence. In our opinion, the choice of either of these fixation methods during surgery should not be based on the concerns of pain or recurrence. AT may be the preferable option in LVIHR due to the lower cost.


title: High fidelity of murine hepatitis virus replication is decreased in nsp14 exoribonuclease mutants.

text: Replication fidelity of RNA virus genomes is constrained by the opposing necessities of generating sufficient diversity for adaptation and maintaining genetic stability, but it is unclear how the largest viral RNA genomes have evolved and are maintained under these constraints. A coronavirus (CoV) nonstructural protein, nsp14, contains conserved active-site motifs of cellular exonucleases, including DNA proofreading enzymes, and the severe acute respiratory syndrome CoV (SARS-CoV) nsp14 has 3'-to-5' exoribonuclease (ExoN) activity in vitro. Here, we show that nsp14 ExoN remarkably increases replication fidelity of the CoV murine hepatitis virus (MHV). Replacement of conserved MHV ExoN active-site residues with alanines resulted in viable mutant viruses with growth and RNA synthesis defects that during passage accumulated 15-fold more mutations than wild-type virus without changes in growth fitness. The estimated mutation rate for ExoN mutants was similar to that reported for other RNA viruses, whereas that of wild-type MHV was less than the established rates for RNA viruses in general, suggesting that CoVs with intact ExoN replicate with unusually high fidelity. Our results indicate that nsp14 ExoN plays a critical role in prevention or repair of nucleotide incorporation errors during genome replication. The established mutants are unique tools to test the hypothesis that high replication fidelity is required for the evolution and stability of large RNA genomes.


title: Serologic survey for canine coronavirus in wolves from Alaska.

text: Wolves (Canis lupus) were captured in three areas of Interior Alaska (USA). Four hundred twenty-five sera were tested for evidence of exposure to canine coronavirus by means of an indirect fluorescent antibody procedure. Serum antibody prevalence averaged 70% (167/240) during the spring collection period and 25% (46/185) during the autumn collection period. Prevalence was 0% (0/42) in the autumn pup cohort (age 4-5 mo), and 60% (58/97) in the spring pup cohort (age 9-10 mo). Prevalence was lowest in the Eastern Interior study area. A statistical model indicates that prevalence increased slightly each year in all three study areas. These results indicate that transmission occurs primarily during the winter months, antibody decay is quite rapid, and reexposure during the summer is rare.


docid: wbkmdvmr

title: Exposure of free-ranging maned wolves (Chrysocyon brachyurus) to infectious and parasitic disease agents in the Noël Kempff Mercado National Park, Bolivia.

text: Maned wolves (Chrysocyon brachyurus) are neotropic mammals, listed as a CITES Appendix II species, with a distribution south of the Amazon forest from Bolivia, through northern Argentina and Paraguay and into eastern Brazil and northern Uruguay. Primary threats to the survival of free-ranging maned wolves include habitat loss, road kills, and shooting by farmers. An additional threat to the conservation of maned wolves is the risk of morbidity and mortality due to infectious and parasitic diseases. Captive maned wolves are susceptible to, and die from, common infectious diseases of domestic dogs (Canis familiaris) including canine distemper virus (CDV), canine parvovirus (CPV), rabies virus, and canine adenovirus (CAV). Results from this study show that free-ranging maned wolves in a remote area of Bolivia have been exposed to multiple infectious and parasitic agents of domestic carnivores, including CAV, CDV, CPV, canine coronavirus, rabies virus, Leptospira interrogans spp., Toxoplasma gondii, and Dirofilaria immitis, and may be at increased risk for disease due to these agents.


title: Morphological and intracellular alterations induced by cytotoxin VT2y produced by Escherichia coli isolated from chickens with swollen head syndrome.

text: Recently, a novel verocytotoxin named VT2y was described which belongs to the STx family and is produced by Escherichia coli isolated from domestic poultry with swollen head syndrome (SHS). The VT2y toxin induced apoptosis in Vero, HeLa, CHO, CEF (primary chicken embryo fibroblast) and PCK (primary chicken kidney) cell lines. Morphological evidence (nuclear shrinkage, chromatin condensation and blebbing of the plasma membrane) of apoptosis could be distinguished in 15 min and was maximal at 1 h after treatment with VT2y. This was confirmed by the terminal dUTP nick-end-labeling (TUNEL) method.


title: Sequential changes of serum aminotransferase levels in patients with severe acute respiratory syndrome.

text: Severe acute respiratory syndrome (SARS) is a newly emerging infectious disease. To describe the hepatic injury caused by this disease, we report the sequential changes of serum transaminase in probable SARS patients during a hospital outbreak in southern Taiwan. From April to June, 2003, 52 probable SARS patients were hospitalized. Serial serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were retrospectively analyzed and hepatitis B surface antigen (HBsAg) was also evaluated to correlate with the progression of this disease. Fifty-three percent of the patients had abnormal liver function during hospitalization. More than 70% of abnormal transaminase levels were mildly elevated. Most elevated levels were noted during the second week after onset of fever. Neither transaminase elevation nor HBsAg was related to the prognosis of SARS, and only advanced age was an independent predictor of poor outcome. Our study suggested that coronavirus causing SARS might induce liver damage.


title: Eighty years of the Slovenian Institute of Public Health: challenges for the future.

text: Eighty years after the first national public health institution was founded in Slovenia, the Institute of Public Health of the Republic of Slovenia (IPHRS) endeavors to meet ever-growing national demands. With the independence of Slovenia in 1991, new tasks had to be tackled, many of which were initially coupled with typical difficulties of a postcommunist country in transition. Also, increasing demands of the European Union (EU) and other international partners had to be met. The IPHRS monitors the health of the Slovenian population and its determinants and contributes to planning and implementation of population-based interventions for the better health of the whole nation. The diversity of the IPHRS activities is mirrored by the organization's internal complexity, multi-disciplinary approach, and links to various sectors. Currently, activities are organized within five centers: Center for Population Health Research; Center for Health Care Organization, Economics and Informatics; Center for Environmental Health; Center for Communicable Diseases; and Center for Health Promotion. The IPHRS is the key national institution in public health research, which is an integral part of all the areas covered by the Institute. The IPHRS also provides education programs in the field of public health. In the near future, it will be important to sustain current activities while integrating into the new program of Community action in the field of public health as well as contributing to the response to challenging public health issues in the wider context of the whole European region. Our aim is to integrate the Institute's activities in the programs relevant to public health issues of outstanding importance in this European sub-region. The IPHRS, given the geographic position and recent history, can act as an intermediate between the public health networks in EU and other countries in the sub-region.


Elucidation of the genomic nucleotide sequence of bovine coronavirus and analysis of cryptic leader mRNA fusion sites.


title: Detection of bovine torovirus in fecal specimens of calves with diarrhea in Japan.

text: The aim of this study was to determine the prevalence of bovine torovirus (BoTV) in bovine fecal samples and to determine whether a relationship exists between BoTV and diarrhea in Japan. Ninety-nine diarrheic and 114 normal fecal samples from calves in Hokkaido Prefecture and 38 diarrheic fecal samples from calves in 10 other prefectures were examined by reverse transcription (RT)-PCR with primers designed in the spike (S) gene for the presence of BoTV. The specimens were also examined for the presence of other enteric pathogens, bovine rotavirus, coronavirus and Cryptosporidium spp. BoTV RNA was detected in 15 (15.2%) of the 99 diarrheic samples from Hokkaido and in 9 (23.7%) of the 38 diarrheic samples from the other prefectures. The incidence of BoTV in control specimens was 7.0%. In 11 of the 15 BoTV-positive specimens from Hokkaido, BoTV was the only pathogen detected among those examined, and 11 BoTV-positive specimens were obtained from calves less than 2 weeks of age. Rotavirus was confirmed to be associated with calf diarrhea, but coronavirus and Cryptosporidium spp. were not. Nucleotide sequences of 17 different BoTV RT-PCR products were determined. Phylogenetic analysis based on the sequences revealed that Japanese BoTVs could be classified into at least two groups. This study showed that BoTV is a common virus in fecal specimens of calves with diarrhea in Japan and may be an important pathogen of cattle, principally in young calves less than 2 weeks of age.


title: Crystal structure of norwalk virus polymerase reveals the carboxyl terminus in the active site cleft.

text: Norwalk virus is a major cause of acute gastroenteritis for which effective treatments are sorely lacking. To provide a basis for the rational design of novel antiviral agents, the main replication enzyme in Norwalk virus, the virally encoded RNA-dependent RNA polymerase (RdRP), has been expressed in an enzymatically active form, and its structure has been crystallographically determined both in the presence and absence of divalent metal cations. Although the overall fold of the enzyme is similar to that seen previously in the RdRP from rabbit hemorrhagic disease virus, the carboxyl terminus, surprisingly, is located in the active site cleft in five independent copies of the protein in three distinct crystal forms. The location of this carboxyl-terminal segment appears to interfere with the binding of double-stranded RNA in the active site cleft and may play a role in the initiation of RNA synthesis or mediate interactions with accessory replication proteins.


[CORONA INFECTION DURING PREGNANCY].


Ebola Virus Disease: Are We Prepared?


title: Using HealthMap to Analyse Middle East Respiratory Syndrome (MERS) Data.

text: In this paper, a web-based disease surveillance platform known as HealthMap is used to retrieve and analyze data pertaining to the Middle East Respiratory Syndrome (MERS) within the geographical confinements of the Arab World and North African countries. An account was opened with HealthMap to gain access to data related to MERS for the time-period 9 September 2015 to 7 March 2015. HealthMap accumulates and assesses outbreak data from a range of sources, this includes news media (Google News (Arabic)), validated official alerts (WHO) and expert-curated accounts (ProMED). Search terms "MERS" and "Coronavirus" were used to search HealthMap for relevant alerts pertaining to MERS. The search terms were geographically limited to the Arab World and North African countries. Our results show that the prevalence of MERS still remains to be the highest in Saudi Arabia, however, between 9 September 2015 and 7 March 2015 there has been a slight overall trend in decreasing number of MERS related alerts within Saudi Arabia and the Arab world. All countries other than Saudi Arabia such as, UAE, Tunisia, Qatar, Oman, Lebanon, Kuwait, Jordan and Egypt together amounted for only 25.6% (n=214) of total MERS alerts (n=837). Our findings show that the rise in the aggregated contribution of internet based participatory surveillance systems for tracking non-communicable diseases such as MERS has aided in improving the accuracy, sensitivity and timeliness for monitoring disease outbreaks. Use of resources such as HealthMap can aid in the timely assessment of risk factors, vaccination development initiatives, prevention strategies and measured allocation of healthcare resources while running at a low cost with greater flexibility and increased scalability compared to isolated diseases surveillance systems.


title: Isolation and characterization of new infectious bronchitis virus variants in Hungary.

text: Two agents not agglutinating chicken erythrocytes were isolated, one in each of two flocks, from organ samples and tracheal swabs taken from 4- to 7-week-old chicks of 8 broiler flocks experiencing respiratory signs. Virus isolation was done in embryonated SPF hen's eggs. Morphological changes of the embryos, appearing as dwarfing or curling into a spherical form, usually occurred in the 3rd or 4th passage on postinoculation (PI) days 5-9. Some embryos had swollen kidneys covered with urate. Electron microscopy of ultrathin sections of these kidneys revealed the presence of virions reminiscent of coronaviruses. Similar viral particles were seen in resuspended pellets of isolates concentrated by ultracentrifugation. Based on embryo changes, cross-neutralization tests with type-specific antisera, physicochemical tests, results obtained in cell cultures, and electron microscopic findings the two isolates were identified as infectious bronchitis virus (IBV). By cross-neutralization tests the isolates differed from IBV reference strains M41 and H52 and can be considered distinct variants. Elucidation of their epizootiological role requires further investigations.


docid: armpvrzk

title: Screening of specific antigens for SARS clinical diagnosis using a protein microarray.

text: In this study several SARS-CoV structural proteins and fragments were expressed in E. coli as GST or TRX fusion proteins. They were fabricated on a microarray and tested with sera from SARS patients. Antigenic screening indicated that recombinant GST-N2 fusion protein, the carboxy-terminus 213aa-423aa of N protein, was strongest positive and weakest non-specific compared with others. An indirect antibody ELISA method was developed and clinical positive and negative sera for their antibodies against GST-N2 fusion protein were assayed. 311 out of the 442 sera from clinical SARS inpatients, as well as 229 out of 302 sera from convalescent patients gave positive reactivities; positive rates were 70.4% and 75.8% respectively. Sera from a total of 2726 non-SARS patients and healthy individuals were tested and the false positive rate was only 0.07%. When the sensitivity control sample was diluted 1 : 64, it yielded OD values above the cutoff value. Reported data showed that this was a relatively high degree of sensitivity and specificity for SARS-CoV antibody testing. The data indicate that GST-N2 fusion protein, which was screened by protein microarray, may be a valuable diagnostic antigen for the development of serological assays for SARS. In addition, protein microarray assay presents a higher positive rate and sensitivity (86.1% and 1 : 200) compared with the traditional ELISA screening method, and could provide a rapid, parallel and high-throughput antigen screening platform.


docid: wdaajfjs

title: [Determination of serum acute phase reaction protein in patients with severe acute respiratory syndrome].

text: OBJECTIVE To study the diagnostic value of determinations of serum acute phase reaction protein, such as complement 3 (C3), complement 4 (C4), prealbumin (PA) and C-reactive protein (CRP), etc., in patients with severe acute respiratory syndrome (SARS). METHODS Serum levels of C3, C4, PA and CRP were determined by turbidimetry in 54 cases of SARS, 20 of other pneumonia and 30 normal persons. RESULTS Serum concentrations of C3, C4, CRP and PA were (1.18 +/- 0.42) g/L, (1.15 +/- 0.56) g/L, (10.52 +/- 8.77) mg/L and (107 +/- 54) mg/L in SARS patients, (1.30 +/- 0.46) g/L, (0.57 +/- 0.31) g/L, (0.88 +/- 0.43) mg/L and (291 +/- 76) mg/L in patients with other pneumonia, and (1.11 +/- 0.56) g/L, (0.38 +/- 0.26) g/L, (0.42 +/- 0.26) mg/L and (376 +/- 74) mg/L in normal persons, respectively. Serum level of PA was significantly lower and levels of C4 and CRP significantly in patients with SARS higher than those in patients with other pneumonia and normal persons (P < 0.01). There was no significant difference in serum level of C3 between the three groups (P > 0.05). CONCLUSION Determination of serum level of C4, CRP and PA in suspected patients is beneficial to early differential diagnosis for SARS.


title: Pathology of an atypical strain of Pasteurella gallinarum infection in chickens.

text: Gross and microscopic pathology caused by an atypical strain of Pasteurella gallinarum (Fresno strain) was compared in chickens with that caused by the American Type Culture Collection type strain. Ten 21-day-old broiler chickens were inoculated intranasally with 10(7) colony forming units or intramuscularly with 10(5) colony forming units of either strain. The birds were killed 7 days later, and gross and microscopic lesions were studied. Grossly, there was extensive white discoloration of pectoral muscles with mild fibrinous exudate in birds inoculated intramuscularly with the Fresno strain of P. gallinarum. Most of these birds also had severe fibrinous exudation over the heart, the capsule of the liver, the air sac, and in the hock joints. Microscopically, there was severe chronic pyogranulomatous airsacculitis, pericarditis, perihepatitis, myositis, synovitis, and granulomatous pneumonia. One bird had severe acute multifocal hepatitis. From this study, it is evident that the Fresno strain of P. gallinarum was more pathogenic than the American Type Culture Collection type strain when given intramuscularly.


title: Measles virus preferentially transduces the basolateral surface of well-differentiated human airway epithelia.

text: Measles virus (MV) is typically spread by aerosol droplets and enters via the respiratory tract. The progression of MV infection has been widely studied; yet, the pathway for virus entry in polarized human airway epithelia has not been investigated. Herein we report the use of a replication-competent Edmonston vaccine strain of MV expressing enhanced green fluorescent protein (MV-eGFP) to infect primary cultures of well-differentiated human airway epithelia. Previous studies with polarized Caco-2 cells (intestine-derived human epithelia) and MDCK cells (kidney-derived canine epithelia) demonstrated that MV primarily infected and exited the apical surface. In striking contrast, our results indicate that MV preferentially transduces human airway cells from the basolateral surface; however, virus release remains in an apical direction. When MV-eGFP was applied apically or basolaterally to primary cultures of airway epithelia, discrete foci of eGFP expression appeared and grew; however, the cell layer integrity was maintained for the duration of the study (7 days). Interestingly, utilizing immunohistochemistry and confocal microscopy, we observed widespread expression of the receptor for the vaccine strain of MV (CD46) at greatest abundance on the apical surface of the differentiated human airway epithelia as well as in human tracheal tissue sections. These data suggest that the progression of MV infection through the respiratory epithelium may involve pathways other than direct binding and entry through the apical surface of airway epithelia.


International criminal prosecution of physicians: a critique of Professors Annas and Grodin's proposed International Medical Tribunal.


Synergy between public health and veterinary services to deliver human and animal health interventions in rural low income settings.


title: Bats are natural reservoirs of SARS-like coronaviruses.

text: Severe acute respiratory syndrome (SARS) emerged in 2002 to 2003 in southern China. The origin of its etiological agent, the SARS coronavirus (SARS-CoV), remains elusive. Here we report that species of bats are a natural host of coronaviruses closely related to those responsible for the SARS outbreak. These viruses, termed SARS-like coronaviruses (SL-CoVs), display greater genetic variation than SARS-CoV isolated from humans or from civets. The human and civet isolates of SARS-CoV nestle phylogenetically within the spectrum of SL-CoVs, indicating that the virus responsible for the SARS outbreak was a member of this coronavirus group.


title: Prevalence and implications of feline coronavirus infections of captive and free-ranging cheetahs (Acinonyx jubatus).

text: The extent and progression of exposure to feline infectious peritonitis (FIP) virus in the cheetah, Acinonyx jubatus, was monitored by a world-wide serological survey with indirect fluorescent antibody titers to coronavirus. The indirect fluorescent antibody assay was validated by Western blots, which showed that all indirect fluorescent antibody-positive cheetah sera detected both domestic cat and cheetah coronavirus structural proteins. There was a poor correlation between indirect fluorescent antibody results and the presence of coronaviruslike particles in cheetah feces, suggesting that electron microscopic detection of shed particles may not be an easily interpreted diagnostic parameter for FIP disease. Low, but verifiable (by Western blots [immunoblots]) antibody titers against coronavirus were detected in eight free-ranging cheetahs from east Africa as well as from captive cheetahs throughout the world. Of 20 North American cheetah facilities screened, 9 had cheetahs with measurable antibodies to feline coronavirus. Five facilities showed patterns of an ongoing epizootic. Retrospective FIP virus titers of an FIP outbreak in a cheetah-breeding facility in Oregon were monitored over a 5-year period and are interpreted here in terms of clinical disease progression. During that outbreak the morbidity was over 90% and the mortality was 60%, far greater than any previously reported epizootic of FIP in any cat species. Age of infection was a significant risk factor in this epizootic, with infants (less than 3 months old) displaying significantly higher risk for mortality than subadults or adults. Based upon these observations, empirical generalizations are drawn which address epidemiologic concerns for cheetahs in the context of this lethal infectious agent.


title: Phosphoproteins of murine hepatitis viruses.

text: Four strains of the coronavirus murine hepatitis virus were examined for the presence of phosphorylated proteins. The nucleocapsid protein was determined to contain phosphate covalently linked to serine but not to threonine residues. The nucleocapsid protein was the only phosphorylated protein detected in these strains of murine hepatitis virus.


title: Cleavage inhibition of the murine coronavirus spike protein by a furin-like enzyme affects cell-cell but not virus-cell fusion.

text: Cleavage of the mouse hepatitis coronavirus strain A59 spike protein was blocked in a concentration-dependent manner by a peptide furin inhibitor, indicating that furin or a furin-like enzyme is responsible for this process. While cell-cell fusion was clearly affected by preventing spike protein cleavage, virus-cell fusion was not, indicating that these events have different requirements.


docid: rkhgjvae

title: [Expression, purification and antibody preparation of recombinat SARS-CoV X5 protein].

text: X5 protein is one of the putative unknown proteins of SARS-CoV. The recombinant protein has been successfully expressed in E. coli in the form of insoluble inclusion body. The inclusion body was dissolved in high concentration of urea. Affinity Chromatography was preformed to purify the denatured protein, and then the product was refolded in a series of gradient solutions of urea. The purified protein was obtained with the purity of > 95% and the yield of 93.3 mg x L(-1). Polyclonal antibody of this protein was obtained, and Western blotting assay indicated that the X5 protein has the strong property of antigen. Sixty-eight percent of the recombinant protein sequence was confirmed by LC-ESI-MS/MS analysis.


title: The safety and efficacy of peripheral vascular procedures performed in the outpatient setting.

text: OBJECTIVES This study sought to evaluate the safety and efficacy of peripheral vascular interventions performed in a private, outpatient catheterization laboratory. BACKGROUND Peripheral vascular interventions have been traditionally performed in the inpatient setting. However, there has been a recent shift away from hospital-based vascular interventions toward outpatient-based procedures. Data are scarce on the efficacy and safety of such procedures being performed in the outpatient setting. METHODS We performed a retrospective chart review of the first 500 consecutive procedures that were performed at an outpatient catheterization laboratory from February 2012 through February 2013. We separated the procedures into arteriovenous fistula (AVF)-related procedures, peripheral arterial disease (PAD)-related procedures, and miscellaneous procedures. The primary endpoint was procedure success rate, defined as postintervention residual stenosis of <30% on angiography. The secondary endpoint was procedure-related adverse events. RESULTS The success rate for AVF-related interventions was 90%, and 93% when including partially successful interventions. The success rate for PAD-related interventions was 82%, and 92% when including partially successful interventions. The procedure success rate for miscellaneous interventions was 89%. Five AVF-related procedures suffered an adverse event (1.49%). Two PAD-related procedures suffered an adverse event (1.3%), while no adverse events were noted among miscellaneous procedures. One patient required immediate postprocedure hospitalization due to iliac artery perforation. CONCLUSION Peripheral vascular procedures performed in the outpatient setting are safe and effective. A comparison of outcomes between outpatient and inpatient facilities when performing similar peripheral vascular interventions is needed in order to determine whether a transition of further vascular procedures into an outpatient setting is justified.


title: Effects of lactoferrin-containing formula in the prevention of enterovirus and rotavirus infection and impact on serum cytokine levels: a randomized trial.

text: BACKGROUND Lactoferrin has been shown to exhibit anti-enterovirus 71 (EV71) and antirotavirus properties. This trial was conducted to determine whether a formula containing bovine lactoferrin (bLF) exerts a protective effect against EV71 or rotavirus infection among children from 2 to 6 years old. METHODS A prospective, randomized, single blind clinical trial of an oral supplement containing bLF (daily dose approximately 70 to 85 mg) was carried out with healthy children in a day care center from March 2002 to June 2003. The incidence of enterovirus or rotavirus infection and the serum level of interferon- gamma (IFN-γ) and interleukin-10 (IL-10) were compared between children receiving and not receiving bLF. RESULTS A total of 172 children, 96 in group A, which received bLF, and 76 in group B which did not receive bLF, completed the trial. During the study period, no EV71 was isolated and seroconversion of EV71 antibodies was noted in only one child. Fourteen episodes of presumptive enterovirus infection and 12 episodes of presumptive viral enteritis were detected. No significant differences were observed between groups in the incidence of presumptive enterovirus infection or viral enteritis or the number of laboratory confirmed enterovirus or rotavirus infections. No significant differences were observed in the serum levels of IFN-γ and IL-10 between groups either prior to or following the trial. In both groups, IFN-γ levels increased, but IL-10 was unchanged following the trial. CONCLUSION An oral supplement of bLF at a dose of 70 mg/day did not show any benefits in the prevention of EV71 or rotavirus infection, or any impact on IFN-γ or IL-10 serum levels in healthy children in this trial.


Retraction of an interpretation.


title: Depression in primary care.

text: Depression is common in primary care settings, affecting at least 10% of primary care patients. It carries medical and psychiatric comorbidity, increasing the risk of cardiovascular disease, diabetes, hypertension, stroke, medically unexplained (functional) symptoms, chronic pain, anxiety disorders, and substance abuse. Diagnosis and treatment are straightforward for many patients. The greatest current challenge is to recognize and relieve symptoms of treatment-resistant depression. This article reviews current approaches to diagnosing and treating depression, especially treatment-resistant forms of depression.


title: Non-invasive versus invasive mechanical ventilation for respiratory failure in severe acute respiratory syndrome.

text: BACKGROUND Severe acute respiratory syndrome is frequently complicated by respiratory failure requiring ventilatory support. We aimed to compare the efficacy of non-invasive ventilation against invasive mechanical ventilation treating respiratory failure in this disease. METHODS Retrospective analysis was conducted on all respiratory failure patients identified from the Hong Kong Hospital Authority Severe Acute Respiratory Syndrome Database. Intubation rate, mortality and secondary outcome of a hospital utilizing non-invasive ventilation under standard infection control conditions (NIV Hospital) were compared against 13 hospitals using solely invasive ventilation (IMV Hospitals). Multiple logistic regression analyses with adjustments for confounding variables were performed to test for association between outcomes and hospital groups. RESULTS Both hospital groups had comparable demographics and clinical profiles, but NIV Hospital (42 patients) had higher lactate dehydrogenase ratio and worse radiographic score on admission and ribavirin-corticosteroid commencement. Compared to IMV Hospitals (451 patients), NIV Hospital had lower adjusted odds ratios for intubation (0.36, 95% CI 0.164 - 0.791, P = 0.011) and death (0.235, 95% CI 0.077 - 0.716, P = 0.011), and improved earlier after pulsed steroid rescue. There were no instances of transmission of severe acute respiratory syndrome among health care workers due to the use of non-invasive ventilation. CONCLUSION Compared to invasive mechanical ventilation, non-invasive ventilation as initial ventilatory support for acute respiratory failure in the presence of severe acute respiratory syndrome appeared to be associated with reduced intubation need and mortality.


Protective effect of orally administered immunoglobulins against experimental calf diarrhea.


Health sector challenges and responses beyond the Alma-Ata Declaration: a Caribbean perspective.


Guanosine triphosphatase activity of the human coronavirus helicase.


title: Mutation analysis of 20 SARS virus genome sequences: evidence for negative selection in replicase ORF1b and spike gene.

text: AIM Recently, more SARS-CoV virus genome sequences are released to the GenBank database. The aim of this study is to reveal the evolution forces of SARS-CoV virus by analyzing the nucleotide mutations in these sequences. METHODS We obtained 20 SARS-CoV virus genome sequences from NCBI database, and calculated the ratio of non-synonymous nucleotide substitution per non-synonymous site (Ka) and synonymous nucleotide substitution per synonymous site (Ks) for SARS-CoV virus genes. RESULTS The Ka/Ks ratios for replicase polyprotein ORF1a, ORF1b, and spike protein gene are 1.09 (P=0.6501), 0.38 (P=0.0074), 0.65 (P=0.0685) respectively. CONCLUSION SARS-CoV virus replicase polyprotein ORF1b is undergoing negative selection; negative selection force is also probably operating on spike protein gene. These results provide basis for future developing a new drug and vaccine against SARS.


Going Viral: Doctors Must Combat Fake News in the Fight against Covid-19.


Perceived threats and real killers.


Misleading behavior of Masimo pulse oximeter tone during profound bradycardia.


title: A history of One Health.

text: One Health is not a new concept. It can be demonstrated that its origins and development literally run the gamut from A to Z, that is to say, from Aristotle to Zoobiquity. Indeed, the consequences of the interaction that occurs between ecosystems, animals and people have shaped, and continue to shape, the course of human events and history. A reasoned and evidence-based assessment of the history of One Health must first be founded on an agreed definition of the term, but, given the many disciplines and sciences involved, finding such a definition is no easy task. Furthermore, there is an extensive and growing list of visionary individuals who have, over the centuries, attempted to promote awareness and advance the conceptto improve the management of the risks and consequences that arise at the interface between animal, human and ecosystem health. The One Health ideas of the 21st Century constitute a re-conceptualisation of health management in response to the accelerating environmental changes of the past 100 years, changes that are associated with the parallel exponential growth and concentration of the global human population. Consequently, the concept of One Health must recognise the constantly evolving relationship between animals and humans and the planet they share.


title: Transcriptional strategy of closteroviruses: mapping the 5' termini of the citrus tristeza virus subgenomic RNAs.

text: Citrus tristeza virus (CTV) induces formation of a nested set of at least nine 3' coterminal subgenomic RNAs (sgRNAs) in infected tissue. The organization and expression of the 19,296-nucleotide (nt) CTV genome resembles that of coronaviruses, with polyprotein processing, translational frameshifting, and multiple sgRNA formation, but phylogenetically the CTV polymerase, like polymerases of other closteroviruses, belongs to the Sindbis virus-like lineage of RNA virus polymerases. Both positive-strand RNA virus supergroups, coronaviruses and Sindbis-like viruses, utilize different mechanisms of transcription. To address the mechanism of CTV transcription, 5' termini for the two most abundant sgRNAs, 1.5 and 0.9 kb, respectively, were mapped by runoff reverse transcription. The two sgRNAs were demonstrated to have 48- and 38-nt 5' untranslated regions (5'-UTRs), respectively. The 5'-UTR for the 1.5-kb RNA was cloned, sequenced, and demonstrated to be colinear with the 48-nt genomic sequence upstream of the initiator codon of the respective open reading frame 10, i.e., to be of continuous template origin. The data obtained suggest that the sgRNA transcription of CTV is dissimilar from the coronavirus transcription and consistent with the transcriptional mechanism of other Sindbis-like viruses. Thus, the Sindbis virus-like mechanism of transcription of the positive-strand RNA genomes might be successfully utilized by the closterovirus genome of up to 19.3 kb with multiple sgRNAs.


title: The two fACEs of the tissue renin-angiotensin systems: implication in cardiovascular diseases.

text: The implication of the renin-angiotensin system (RAS) in the regulation of the cardiovascular system has been well known for many years. Accordingly, many pharmaceutical inhibitors have been developed to treat several pathologies, like hypertension and heart failure, and angiotensin converting enzyme (ACE) became one of the major target in the treatment of these cardiovascular diseases. In the last decade however, it has become apparent that the classical view of the RAS was not quite accurate. For instance, ACE has been shown to work not only by generating angiotensin-II but also by interacting with receptors outside the renin-angiotensin system. Moreover, it has been shown that many local RAS are present in different tissues, such as the heart, brain, kidney and vasculature. However, in the past, it was impossible to determine the role of these local systems as they were pharmacologically indistinguishable from the systemic RAS. Hence, in recent years, the development of transgenic animals has allowed us to determine that these local systems are implicated in the roles that had been originally attributed exclusively to the systemic action of the RAS. However, with almost 30% of the medicated hypertensive patients harboring an uncontrolled blood pressure, a need for new drugs and new targets appears necessary. With the new century came the discovery of a new homolog of ACE, called ACE2, and early studies suggest that it may play a pivotal role in the RAS by controlling the balance between the vasoconstrictor effects of angiotensin-II and the vasodilatory properties of the angiotensin(1-7) peptide. Like ACE, ACE2 appears to hydrolyze peptides not related with the RAS and the enzyme has also been identified as a receptor for the severe acute respiratory syndrome (SARS) coronavirus. Although the tissue localization of ACE2 was originally though to be very restricted, new studies have emerged showing a more widespread distribution. Therefore, the whole dynamics of the RAS has to be re-evaluated in light of this new information. In this review, we will compare the structures, distributions and properties of ACE and its new homologue in the context of cardiovascular function, focusing on the autocrine/paracrine cardiac and brain renin-angiotensin systems and we will present recent data from the literature and our laboratory offering a new perspective on this potential target for the treatment of cardiovascular diseases.


docid: spaipgdw

title: A comparative study of nasopharyngeal aspirate and nasal swab specimens for the diagnosis of acute viral respiratory infection.


Bioterrorism: a clear and present danger.


title: Breastfeeding-related maternity practices at hospitals and birth centers--United States, 2007.

text: Breastfeeding provides optimal nutrition for infants and is associated with decreased risk for infant and maternal morbidity and mortality; however, only four states (Alaska, Montana, Oregon, and Washington) have met all five Healthy People 2010 targets for breastfeeding. Maternity practices in hospitals and birth centers throughout the intrapartum period, such as ensuring mother-newborn skin-to-skin contact, keeping mother and newborn together, and not giving supplemental feedings to breastfed newborns unless medically indicated, can influence breastfeeding behaviors during a period critical to successful establishment of lactation. In 2007, to characterize maternity practices related to breastfeeding, CDC conducted the first national Maternity Practices in Infant Nutrition and Care (mPINC) Survey. This report summarizes results of that survey, which indicated that 1) a substantial proportion of facilities used maternity practices that are not evidence-based and are known to interfere with breastfeeding and 2) states in the southern United States generally had lower mPINC scores, including certain states previously determined to have the lowest 6-month breastfeeding rates. These results highlight the need for U.S. hospitals and birth centers to implement changes in maternity practices that support breastfeeding.


title: RNA-dependent RNA polymerase activity in coronavirus- infected cells.

text: An enzymatic activity which incorporates [3H]UMP into acid-precipitable material in the presence of endogenous template was found in the cytoplasm of porcine cells infected with the transmissible gastroenteritis virus of swine. This activity was not found in uninfected control cells, nor was it found in purified virus. The activity was associated with the mitochondrial fraction of infected cells, suggesting that the enzyme is membrane bound. The activity required the presence of all three ribonucleoside triphosphates in addition to [3H]UTP, and it was not inhibited by actinomycin D. The heated product was digested by RNase but not by DNase. Mg2+ was required for enzymatic activity, and its optimal concentration was approximately 5 mM. The size of the in vitro products was compared by electrophoresis with that of in vivo-synthesized virus-specified RNA to confirm the viral specificity of the polymerase activity. Virus-specified RNA from infected cells consisted of 10 species of single-stranded, polyadenylated RNA with molecular weights of 6.8 X 10(6), 6.2 X 10(6), 3.15 X 10(6), 1.40 X 10(6), 1.05 X 10(6), 0.94 X 10(6), 0.66 X 10(6), 0.39 X 10(6), 0.34 X 10(6), and 0.24 X 10(6). In vitro synthesized RNA consisted of a high-molecular-weight species, of apparently higher molecular weight than genomic RNA, and two single-stranded species that electrophoretically comigrated with the species of 1.40 X 10(6) and 0.66 X 10(6) molecular weight made in vivo.


title: Consideration of the respiratory support strategy of severe acute respiratory failure caused by SARS-CoV-2 infection in children.

text: The recent ongoing outbreak of severe pneumonia associated with a novel coronavirus (SARS-CoV-2), currently of unknown origin, creates a world emergency that has put global public health institutions on high alert. At present there is limited clinical information of the SARS-CoV-2 and there is no specific treatment recommended, although technical guidances and suggestions have been developed and will continue to be updated as additional information becomes available. Preventive treatment has an important role to control and avoid the spread of severe respiratory disease, but often is difficult to obtain and sometimes cannot be effective to reduce the risk of deterioration of the underlining lung pathology. In order to define an effective and safe treatment for SARS-CoV-2-associated disease, we provide considerations on the actual treatments, on how to avoid complications and the undesirable side effects related to them and to select and apply earlier the most appropriate treatment. Approaching to treat severe respiratory disease in infants and children, the risks related to the development of atelectasis starting invasive or non-invasive ventilation support and the risk of oxygen toxicity must be taken into serious consideration. For an appropriate and effective approach to treat severe pediatric respiratory diseases, two main different strategies can be proposed according to the stage and severity of the patient conditions: patient in the initial phase and with non-severe lung pathology and patient with severe initial respiratory impairment and/or with delay in arrival to observation. The final outcome is strictly connected with the ability to apply an appropriate treatment early and to reduce all the complications that can arise during the intensive care admission.


title: The pre-hospital administration of tranexamic acid to patients with multiple injuries and its effects on rotational thrombelastometry: a prospective observational study in pre-hospital emergency medicine.

text: BACKGROUND Hyperfibrinolysis (HF) is a major contributor to coagulopathy and mortality in trauma patients. This study investigated (i) the rate of HF during the pre-hospital management of patients with multiple injuries and (ii) the effects of pre-hospital tranexamic acid (TxA) administration on the coagulation system. METHODS From 27 trauma patients with pre-hospital an estimated injury severity score (ISS) ≥16 points blood was obtained at the scene and on admission to the emergency department (ED). All patients received 1 g of TxA after the first blood sample was taken. Rotational thrombelastometry (ROTEM) was performed for both blood samples, and the results were compared. HF was defined as a maximum lysis (ML) >15 % in EXTEM. RESULTS The median (min-max) ISS was 17 points (4-50 points). Four patients (15 %) had HF diagnosed via ROTEM at the scene, and 2 patients (7.5 %) had HF diagnosed via ROTEM on admission to the ED. The median ML before TxA administration was 11 % (3-99 %) vs. 10 % after TxA administration (4-18 %; p > 0.05). TxA was administered 37 min (10-85 min) before ED arrival. The ROTEM results before and after TxA administration did not significantly differ. No adverse drug reactions were observed after TxA administration. DISCUSSION HF can be present in severely injured patients during pre-hospital care. Antifibrinolytic therapy administered at the scene is a significant time saver. Even in milder trauma fibrinogen can be decreased to critically low levels. Early administration of TxA cannot reverse or entirely stop this decrease. CONCLUSIONS The pre-hospital use of TxA should be considered for severely injured patients to prevent the worsening of trauma-induced coagulopathy and unnecessarily high fibrinogen consumption. TRIAL REGISTRATION ClinicalTrials.gov ID NCT01938768 (Registered 5 September 2013).


Modulation of cell signalling by human coronavirus HKU1 S and M proteins.


title: [Anosmia and COVID-19].

text: Anosmia associated or not with dysgeusia seems to be a frequent symptom in cases of infection with SARS-CoV-2 responsible for COVID-19. It can be the initial symptom of the disease or remain isolated in pauci-symptomatic patients. Waiting for scientific confirmation and in the context of the current pandemic, it seems essential to consider any patient with a new anosmia as being infected with SARS-CoV-2 until proven otherwise. These patients should therefore isolate themselves and remain alert to the occurrence of other symptoms suggestive of the infection and/or be tested. Topical and systemic corticosteroids and nose washes are contraindicated. The natural course of anosmia seems to be favorable in most cases.


title: SHORT-TERM POSTOPERATIVE COGNITIVE FUNCTION OF ELDERLY PATIENTS UNDERGOING FIRST VERSUS REPEATED EXPOSURE TO GENERAL ANESTHESIA.

text: BACKGROUND General anesthesia (GA) may affect cognitive functions and result in postoperative cognitive dysfunction. The aim of our prospective pilot study was to compare the short-term postoperative cognitive function of unimpaired elderly patients undergoing first versus repeated exposure to GA. METHODS After approval from the Hospital Ethics Committee and informed consent of all participants, 46 patients, 70.1 ± 7.1 years of age, 20 men and 26 women were enrolled in the study. Twenty-five patients belonged to group A (never received GA before) and 21 patients belonged to group B (received at least once GA the last 5 years). Each patient was evaluated preoperatively and the 8th day postoperatively by a blinded examiner with a battery of neurocognitive tests. RESULTS Group B patients performed preoperatively worse in Trail Making Test Part A, Stroop Color and Word Test and Three Words-Three Shapes Test. Postoperatively there were differences in almost every neurocognitive test, with group B patients again achieving the worse scores. This came along with increased Beck Depression Inventory Test score and increased incidence of delirium in Group B patients. CONCLUSION Our pilot study suggests that prior exposure of elderly patients to GA might lead to prolonged cognitive impairment and repeated GA exposure seems to be a potential risk factor for greater short-term postoperative cognitive impairment.


title: Telehealth responses to bio-terrorism and emerging infections.

text: Emerging infectious diseases, such as severe acute respiratory syndrome (SARS), are of huge economic importance. They are difficult to predict. The World Health Organization has a Global Outbreak Alert and Response Network, which was involved at an early stage in the SARS outbreak in 2003. Three major lessons were learned as a result of the SARS epidemic in 2003, involving communication, evidence-based action and global partnerships. It is proposed that a series of broadband global response networks should be developed. At a technical level the networks are essentially in place, such as the Internet2 global network. Suitable peripheral devices also exist. What has not yet been created is the appropriate software to allow the use of these networks, although a number of commercial products are in the process of development.


title: The prospect of silencing disease using RNA interference.

text: The discovery of RNA interference (RNAi), an endogenous cellular gene-silencing mechanism, has already provided a powerful tool for basic science researchers to study gene function. The subsequent finding that RNAi also operates in mammalian cells has generated excitement regarding potential therapeutic applications. In this article we discuss the basic mechanism of RNAi and the therapeutic opportunities and obstacles for harnessing RNAi for therapy of human disease.


title: Siglecs--the major subfamily of I-type lectins.

text: Animal glycan-recognizing proteins can be broadly classified into two groups-lectins (which typically contain an evolutionarily conserved carbohydrate-recognition domain [CRD]) and sulfated glycosaminoglycan (SGAG)-binding proteins (which appear to have evolved by convergent evolution). Proteins other than antibodies and T-cell receptors that mediate glycan recognition via immunoglobulin (Ig)-like domains are called "I-type lectins." The major homologous subfamily of I-type lectins with sialic acid (Sia)-binding properties and characteristic amino-terminal structural features are called the "Siglecs" (Sia-recognizing Ig-superfamily lectins). The Siglecs can be divided into two groups: an evolutionarily conserved subgroup (Siglecs-1, -2, and -4) and a CD33/Siglec-3-related subgroup (Siglecs-3 and -5-13 in primates), which appear to be rapidly evolving. This article provides an overview of historical and current information about the Siglecs.


title: Severe acute respiratory syndrome in pregnancy.

text: BACKGROUND There is limited worldwide experience with severe acute respiratory syndrome (SARS) in pregnancy. We present a case of SARS complicating pregnancy in the third trimester, with outcome data on both the mother and baby. CASE A 33-year-old gravida 2 para 1 fulfilling the World Health Organization case definition for probable SARS was admitted to our institution at 31 weeks of gestation with fever, a dry cough, and patchy infiltrates on chest X-ray. The patient was previously healthy and acquired SARS from close contact with an infected family member. Convalescent serology results were positive for antibodies to coronavirus. She stayed in hospital for 21 days and did not require intensive care admission or ventilatory support. Labor occurred spontaneously at term, and a healthy female baby was delivered with no evidence of infection. CONCLUSION Severe acute respiratory syndrome in pregnancy is a potentially life-threatening illness with complicated management issues. Hospitalization and care by a multidisciplinary team may optimize chances for a good outcome.


title: Healthcare-financing reforms in transitional society: a Shanghai experience.

text: Since the 1950s, China has had a very wide coverage of healthcare service at the local level. In urban areas, the employment-based healthcare-insurance schemes (Government Insurance Scheme and Labour Insurance Scheme) worked hand in hand with the full employment policy of the Government, which guaranteed basic care for almost every urban resident. However, since the economic reforms of the early 1980s, China's healthcare system has met great challenges. Some came from the reform of the labour system, and other challenges came from the introduction of market forces in the healthcare sector. The new policy of the Chinese Government on the Urban Employees' Basic Health Care Insurance is to introduce a cost-sharing plan in urban China. Like other major social policy changes, this new health policy also has a great impact on the lives of the Chinese people. Affordability has been the major concern among urban residents. Shanghai implemented the cost-sharing healthcare policy in the spring of 2001. It may be too early to assess the pros and cons of the new policy, but evidence shows that the employment-based health-insurance scheme excludes those at high risk and in most need. It is argued that the cost-sharing healthcare system will limit access by some people, especially those who are most vulnerable to the consequences of ill health and those in low-income groups, unless the deductibles vary according to income and unless low-income groups are exempt from paying premiums and deductibles.