title: Sacred disease of our times: failure of the infectious disease model of spongiform encephalopathy.

text: BACKGROUND Public health and agricultural policy attempts to keep bovine spongiform encephalopathy out of North America using infectious disease containment policies. Inconsistencies of the infectious disease model as it applies to the spongiform encephalopathies may result in failure of these policies. METHODS Review of historical, political and scientific literature to determine the appropriate disease model of spongiform encephalopathy. PRINCIPAL FINDINGS Spongiform encephalopathy has always occurred sporadically in man and other animals. Hippocrates may have described it in goats and cattle. Transmission of spongiform encephalopathy between individuals is too uncommon for it to be usefully considered an infection. Spongiform encephalopathy is a somatic disorder whose dissemination within a host or transmission between individuals is more like cancer than infectious disease. Spongiform encephalopathy transmission within a species is facilitated in comparison to transmission between species so that cannibalism may amplify the prevalence of the disease. CONCLUSION Agricultural policy should be directed toward an absolute prohibition on occult cannibalism and away from surveillance, quarantine and slaughter, the principal measures of infectious disease containment used to control bovine spongiform encephalopathy.


title: Preparedness of the cardiac catheterization laboratory for severe acute respiratory syndrome (SARS) and other epidemics.

text: Severe acute respiratory syndrome (SARS) is a highly contagious disease that has led to large hospital and community outbreaks, necessitating stringent infection control in its management. Among 90 SARS patients in our institution in the 2003 outbreak, 2 underwent cardiac catheterization. We report the personal respiratory protection and environmental control measures implemented to minimize the risk of droplets spread during these procedures, including re-engineering of the ventilation system of the cardiac catheterization laboratory (CCL). The report highlights the importance of collaboration of CCL personnel with relevant hospital engineering and management teams to develop a contingency infection control plan to prepare for future outbreaks of SARS or other epidemics.


title: Clinical features and molecular epidemiology of coronavirus-HKU1-associated community-acquired pneumonia.

text: 1. Coronavirus (CoV)-HKU1 accounts for 2.4% of community-acquired pneumonia. 2. Clinical features alone cannot differentiate this entity from other community-acquired pneumonia. 3. Further studies are needed to understand the significance of CoV-HKU1 in upper respiratory tract infection and its potential to cause outbreaks of acute viral respiratory illnesses.


title: Applications and optimization of immunization procedures.

text: Classical immunization protocols have produced an antibody-based humoral response that is very effective against susceptible infectious diseases. Immunization introduces an external substance to induce the host immune system to respond specifically. Typically an antigen is used, but DNA, or a primed, pre-existing leukocyte or antigen-presenting cell, can also be used. Immunization is currently being used or investigated for the prevention and treatment of infectious diseases, cancer, addictions, allergies, pregnancy, and autoimmune diseases. It is also being used to produce biologically active materials such as polyclonal and monoclonal antibodies, antivenins, and anti-toxins for treating a wide range of conditions. Animals have been integral to the development of immunization techniques, as producers of toxoids and antitoxins, as models (e.g., to validate materials and protocols used for immunization, to understand the impact of immunization itself on the immune system, and to help investigators devise methods for determining the efficacy of vaccines) and as beneficiaries themselves of vaccines and antitoxins. The choice of immunization protocols is complex, and results may be affected by many factors such as dose and concentration of antigen, choice of adjuvants, time between inoculation and response measurement, and method of detection. The immune system responses to an antigen are also complex and continue to develop with advancing age. Anatomical, physiological, and immune system differences between species influence responses to immunization, as do the purity and presentation of the antigens and adjuvants. When directly comparing results, animals should be sourced from the same supplier. This review highlights the many uses of immunization techniques and introduces important considerations for the choice of protocols and animal models.


title: [Virucidal efficacy of eight disinfectants against pneumovirus, coronavirus and parvovirus].

text: The virucidal activity of 8 disinfectants was analyzed towards 3 groups of viruses responsible for diseases in animals (pneumovirus, coronavirus, parvovirus). Whether organic matter is present or not, parvoviruses are the most resistant, since concentrations of disinfectants 20-500 times higher than those inactivating coronaviruses and pneumoviruses must used. When organic matters are present the activity of disinfectant is considerably reduced. Among the products tested, 0.8% soda and sodium hypochlorite with 1 degree chlorometric were the most active.


title: Acute respiratory distress syndrome.

text: INTRODUCTION Acute respiratory distress syndrome (ARDS) is characterised by lung inflammation with severe hypoxia, which usually develops over 4-48 hours and persists for days or weeks. The main causes of ARDS are infections, aspiration of gastric contents, and trauma. Between a third and a half of people with ARDS die from the disease, but mortality depends on the underlying cause. Some survivors have long-term respiratory or cognitive problems. METHODS AND OUTCOMES We conducted a systematic review and aimed to answer the following clinical question: What are the effects of interventions in adults with acute respiratory distress syndrome? We searched: Medline, Embase, The Cochrane Library and other important databases up to August 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS We found 21 systematic reviews, RCTs, or observational studies that met our inclusion criteria. CONCLUSIONS In this systematic review we present information relating to the effectiveness and safety of the following interventions: corticosteroids, low tidal volume mechanical ventilation, nitric oxide, prone position, and protective ventilation.


title: The ORF7b protein of severe acute respiratory syndrome coronavirus (SARS-CoV) is expressed in virus-infected cells and incorporated into SARS-CoV particles.

text: Coronavirus replication is facilitated by a number of highly conserved viral proteins. The viruses also encode accessory genes, which are virus group specific and believed to play roles in virus replication and pathogenesis in vivo. Of the eight putative accessory proteins encoded by the severe acute respiratory distress syndrome associated coronavirus (SARS-CoV), only two-open reading frame 3a (ORF3a) and ORF7a-have been identified in virus-infected cells to date. The ORF7b protein is a putative viral accessory protein encoded on subgenomic (sg) RNA 7. The ORF7b initiation codon overlaps the ORF7a stop codon in a -1 shifted ORF. We demonstrate that the ORF7b protein is expressed in virus-infected cell lysates and from a cDNA encoding the gene 7 coding region, indicating that the sgRNA7 is bicistronic. The translation of ORF7b appears to be mediated by ribosome leaky scanning, and the protein has biochemical properties consistent with that of an integral membrane protein. ORF7b localizes to the Golgi compartment and is incorporated into SARS-CoV particles. We therefore conclude that the ORF7b protein is not only an accessory protein but a structural component of the SARS-CoV virion.


Histological grading and clinical stage at presentation in breast carcinoma.


title: Evaluation and validation of an enzyme-linked immunosorbent assay and an immunochromatographic test for serological diagnosis of severe acute respiratory syndrome.

text: A newly developed severe acute respiratory syndrome (SARS)-specific enzyme-linked immunosorbent assay (ELISA) was further validated to confirm cutoff values and evaluate its diagnostic performance with clinical samples. In parallel, an immunochromatographic test was also evaluated. A total of 227 clinical serum specimens collected from SARS patients were used in the study, together with 385 samples from healthy donors. By use of an immunofluorescent (IF) test as the "gold standard", both the ELISA and the immunochromatographic test were able to detect immunoglobulin G antibodies to SARS not only from late-convalescent-stage samples (>21 days from the onset of clinical symptoms), as previously established, but also from early-acute-phase samples (1 to 10 days from onset). The ELISA, using an optical density (OD) of 0.25 as its cutoff value, produced the best sensitivity while maintaining high specificity. It detected SARS-specific antibodies in 58, 70, 75, and 95%, respectively, of the four groups of samples collected from patients 1 to 10 days, 11 to 20 days, 21 to 30 days, and more than 30 days after the onset of clinical symptoms. Similarly, the immunochromatographic test detected SARS-specific antibodies in 55, 68, 81, and 79% of the four groups, respectively. The overall specificities for the ELISA and the rapid test were 99.5 and 97.7%, respectively. Although the positive correlation observed between the ELISA OD values and the IF titers was moderate (r = 0.6915; P < 0.001), the detection rates of both the ELISA and the rapid test were found well in agreement with the IF titers.


title: Viral infection at the blood-brain barrier in multiple sclerosis:--an ultrastructural study of tissues from a UK Regional Brain Bank.

text: Although viral infections are often invoked as environmental factors in the aetiology and pathogenesis of multiple sclerosis (MS) it is only recently that a specific, indirect, cytokine-mediated mechanism for triggering of relapses during viral infections has been demonstrated. It is not yet clear however whether this indirect mechanism can account for all reported viral associations with the aetiopathogenesis of MS. A direct causal role of central nervous system (CNS) viral infection in MS has largely been discounted following repeated failures to demonstrate virus within the oligodendrocyte-myelin unit. In the light of increasing evidence of blood-brain barrier (BBB) dysfunction in MS and to further explore the issue of possible viral involvement in MS, an ultrastructural search for viruses was undertaken in the CNS microvasculature, in autopsy and biopsy tissue from human CNS primary demyelinating diseases, including MS (20 cases), idiopathic monophasic CNS demyelinating disease (Mdemy, four cases) and metabolic or immunopathological demyelinating disease (two cases). For comparison, tissues from CNS viral disease in which demyelination is a major feature (nine cases) were examined in the same way. Control CNS tissues (nine cases) from a range of other neurological and non-neurological diseases were also examined. Outside the MS and Mdemy groups, morphological evidence of virus associations with the BBB were found only in the acute and subacute viral encephalitides (three cases subacute sclerosing panencephalitis, one case of Herpes encephalitis) and in one case of disseminated Cytomegalovirus infection. In a small proportion of MS and Mdemy cases, particles resembling either adenovirus (one case of MS) or paramyxovirus (one case of MS, one case of Mdemy) were found in the vicinity of microvessels. In each case a different cell type or extracellular compartment was involved and an exact correlation between the virus particles and the demyelinating lesions could not be demonstrated. Furthermore, corroborative clinical or laboratory evidence of current CNS infection in these primary demyelinating disease cases was available only from the single positive Mdemy case and not from the two cases of MS. This and other previously published evidence from MS (which implicated a Coronavirus) and other diseases highlights the potential vulnerability to viral infection of cells associated with the BBB. Furthermore it is concluded that the detection rate of such infections in pathological tissue could underestimate their true frequency. A possible role of transient virus-BBB interactions in triggering focal inflammation, BBB breakdown and demyelination in some cases of MS and parainfectious demyelinating disease cannot be discounted.


title: COVID-19: Catastrophic Cause of Acute Lung Injury.

text: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak that began in 2019 and spread rapidly across the globe has been observed to cause acute lung injury and multiorgan system failure. While common symptoms are flu-like, this population has been observed to decompensate at an alarmingly rapid rate to severe hypoxia. SARS-CoV-2 infects host cells by targeting the angiotensin-converting enzyme 2 (ACE2) receptor, which is present on endothelial cells in the lung, heart, kidney, and gastrointestinal tissue. The pathophysiology of acute respiratory distress syndrome (ARDS) in SARS-CoV-2 infection has a component of lung perfusion dysregulation and is described as a "cytokine storm" that causes increased vascular permeability and disease severity. Older adults and those with comorbid conditions, particularly hypertension, diabetes, and history of ischemic heart disease, are especially vulnerable. These high-risk populations are often on angiotensin-modulating therapies, which are theorized to increase ACE2 expressivity, but current evidence for or against discontinuation is equivocal. The standard for SARS-CoV-2 testing is through reverse transcription polymerase chain reaction, which has presented problems due to low sensitivity and possible co-infection with other pathogens. Treatment for ARDS in the setting of SARS-CoV-2 should follow pre-established goals of care and the wishes of the patient and family members or caregivers and consider the high risk for polypharmacy, cognitive decline, malnutrition, and depression, particularly in older adults. Treatment recommendations have outlined ventilation goals to minimize further lung injury. Compassionate use of pharmacologic therapies such as remdesivir has shown promise, and further clinical trials of anticytokine agents are underway.


title: Differential maturation and subcellular localization of severe acute respiratory syndrome coronavirus surface proteins S, M and E.

text: Post-translational modifications and correct subcellular localization of viral structural proteins are prerequisites for assembly and budding of enveloped viruses. Coronaviruses, like the severe acute respiratory syndrome-associated virus (SARS-CoV), bud from the endoplasmic reticulum-Golgi intermediate compartment. In this study, the subcellular distribution and maturation of SARS-CoV surface proteins S, M and E were analysed by using C-terminally tagged proteins. As early as 30 min post-entry into the endoplasmic reticulum, high-mannosylated S assembles into trimers prior to acquisition of complex N-glycans in the Golgi. Like S, M acquires high-mannose N-glycans that are subsequently modified into complex N-glycans in the Golgi. The N-glycosylation profile and the absence of O-glycosylation on M protein relate SARS-CoV to the previously described group 1 and 3 coronaviruses. Immunofluorescence analysis shows that S is detected in several compartments along the secretory pathway from the endoplasmic reticulum to the plasma membrane while M predominantly localizes in the Golgi, where it accumulates, and in trafficking vesicles. The E protein is not glycosylated. Pulse-chase labelling and confocal microscopy in the presence of protein translation inhibitor cycloheximide revealed that the E protein has a short half-life of 30 min. E protein is found in bright perinuclear patches colocalizing with endoplasmic reticulum markers. In conclusion, SARS-CoV surface proteins S, M and E show differential subcellular localizations when expressed alone suggesting that additional cellular or viral factors might be required for coordinated trafficking to the virus assembly site in the endoplasmic reticulum-Golgi intermediate compartment.


title: Neuromuscular disorders in severe acute respiratory syndrome.

text: OBJECTIVE To delineate and clarify neuromuscular disorders in patients with probable severe acute respiratory syndrome (SARS). DESIGN Case series with follow-up ranging from 3 weeks to 2 months. SETTING National Taiwan University Hospital, Taipei. PATIENTS We investigated 4 patients with SARS who had concomitant neuromuscular problems. A diagnosis of SARS was based on the demonstration of serum coronavirus antibodies. Clinical presentations, laboratory results, electrophysiologic findings, and follow-up conditions were determined. RESULTS Patients developed neuromuscular problems approximately 3 weeks after the onset of SARS. Two women experienced motor-predominant peripheral nerve disorders. A man developed myopathy and a third woman experienced neuropathy and myopathy. Cerebrospinal fluid obtained from 2 patients with neuropathy disclosed normal protein content and the absence of pleocytosis and SARS coronavirus antibodies. Both patients with myopathy had elevated serum creatine kinase levels. A rapid clinical and electrophysiologic improvement was evident during follow-up examinations, with a good prognosis. CONCLUSIONS The neuromuscular problems in patients with SARS are considered to be critical-illness polyneuropathy or myopathy, possibly coexistent. Further pathological and microbiological studies are necessary to determine the relationship between SARS coronavirus and neuromuscular problems.


title: Protection and immune response in pigs intradermally vaccinated against porcine reproductive and respiratory syndrome (PRRS) and subsequently exposed to a heterologous European (Italian cluster) field strain.

text: The purpose of this study was to assess the immune response in pigs intradermally vaccinated with a commercially available attenuated porcine reproductive and respiratory virus (PRRSV) vaccine (Porcilis PRRS) and subsequently exposed to a heterologous (Italian cluster) field strain of virulent PRRSV. A total of 18, 4-week-old pigs seronegative for PRRSV were allocated to 1 of 3 groups (groups A, B, and C). At 5 weeks of age, pigs of groups A (n=6 pigs) and B (n=6 pigs) were vaccinated intramuscularly and intradermally, respectively, with Porcilis PRRS. The more conventional intramuscular route of vaccination was included for comparative purposes with the intradermal route of vaccination (performed with the I.D.A.L. vaccinator). Pigs of group C (n=6 pigs) were kept as nonvaccinated controls. At post-vaccination (PV) days 7, 14, 21, 28, and 35, blood samples were collected for detection of vaccine virus (PCR) and antibodies (ELISA), and for changes in PBMC (flow cytometry). At PV day 35, pigs of all groups were each exposed (challenged) intranasally to a heterologous field strain (78% ORF5 sequence homology between vaccine and field virus) belonging to the Italian cluster of the European genotype of PRRSV. At post-challenge (PC) days 0, 3, 7, 10, 13, and 17, blood samples were collected for detection and quantitation of virus and antibodies, and for changes in PBMC as described above for blood samples collected PV. Throughout the experiment all pigs were observed daily for clinical signs. At PC days 7 and 17, two pigs and four pigs, respectively, of each group were euthanized and examined for macroscopic lesions. Following vaccination some pigs of groups A and B had a detectable viremia that in two pigs (one pig of group A and one pig of group B) lasted until PV day 28. However, all pigs (groups A, B, and C) remained clinically normal. All vaccinated pigs developed a serological response (ELISA) to PRRSV. Presumptive evidence for vaccine-induced protective immunity against the heterologous challenge strain was provided by finding that viremia following challenge was generally less (incidence) and significantly less (titers) in vaccinated pigs than in nonvaccinated pigs. No differences were apparent between pigs vaccinated intramuscularly and those vaccinated intradermally. The absence of virulent-virus-induced clinical signs and macroscopic lesions in nonvaccinated as well as in vaccinated pigs precluded a more definitive evaluation of the magnitude of protective immunity provided by vaccination or by the route of vaccination. Some likely treatment-associated changes in lymphocyte subpopulations were observed among the three treatment groups. These changes and their potential relationship to protective immunity are discussed.


title: Preliminary crystallographic studies of bacteriophage T4 fibritin confirm a trimeric coiled-coil structure.

text: Fibritin, a 52-kDa product of gene wac of bacteriophage T4, forms fibrous "whiskers" that connect to the phage tail and facilitate the later stages of phage assembly. Preliminary experiments suggest that fibritin is a trimer, and its predominant central part has a parallel alpha-helical coiled-coil structure. To investigate the oligomerization and function of fibritin, we have designed and studied two related deletion mutants, denoted M and E, that consist of its last 75 and 120 amino acids, respectively. Both proteins contain part of the coiled-coil region and the 29 amino acid carboxy-terminal domain essential for the trimerization of fibritin. The proteins are expressed as a soluble product in an Escherichia coli system. We have obtained crystals of fibritins M and E. Complete native X-ray diffraction data sets have been collected to 1.85 and 2.7 A resolution, respectively. The crystals have space group P3 with a=44.3 A, c=91.3 A (fibritin M) and R32 with a=41.2 A, b=358.7 A (fibritin E) in the hexagonal setting. Symmetry and packing considerations show that fibritin is a triple coiled coil.


title: Cross-scale interactions, nonlinearities, and forecasting catastrophic events.

text: Catastrophic events share characteristic nonlinear behaviors that are often generated by cross-scale interactions and feedbacks among system elements. These events result in surprises that cannot easily be predicted based on information obtained at a single scale. Progress on catastrophic events has focused on one of the following two areas: nonlinear dynamics through time without an explicit consideration of spatial connectivity [Holling, C. S. (1992) Ecol. Monogr. 62, 447-502] or spatial connectivity and the spread of contagious processes without a consideration of cross-scale interactions and feedbacks [Zeng, N., Neeling, J. D., Lau, L. M. & Tucker, C. J. (1999) Science 286, 1537-1540]. These approaches rarely have ventured beyond traditional disciplinary boundaries. We provide an interdisciplinary, conceptual, and general mathematical framework for understanding and forecasting nonlinear dynamics through time and across space. We illustrate the generality and usefulness of our approach by using new data and recasting published data from ecology (wildfires and desertification), epidemiology (infectious diseases), and engineering (structural failures). We show that decisions that minimize the likelihood of catastrophic events must be based on cross-scale interactions, and such decisions will often be counterintuitive. Given the continuing challenges associated with global change, approaches that cross disciplinary boundaries to include interactions and feedbacks at multiple scales are needed to increase our ability to predict catastrophic events and develop strategies for minimizing their occurrence and impacts. Our framework is an important step in developing predictive tools and designing experiments to examine cross-scale interactions.


title: Imported human rabies--California, 2008.

text: Compared with rabies in developing countries, human rabies is rare in the United States, but animal rabies is common. In the United States, most human rabies cases are associated with rabid bats, whereas in developing countries, dogs are the most common reservoir and vector species. In March 2008, a case of imported human rabies in a recently arrived, undocumented Mexican immigrant was laboratory confirmed by public health officials in California. The rabies virus isolated from the patient was a previously uncharacterized variant most closely related to viruses found in Mexican free-tailed bats (Tadarida brasiliensis). The molecular and phylogenetic characterizations of this rabies virus variant have been described previously. This report summarizes the epidemiologic investigation and the ensuing public health response. A total of 20 persons, mostly household contacts, received postexposure prophylaxis (PEP) because of potential exposure to rabies virus from the patient. The findings underscore the difficulties encountered in the diagnosis and epidemiologic investigations of imported human rabies cases and the importance of a coordinated public health response across multiple international jurisdictions.


title: Predicted membrane topology of the coronavirus protein E1.

text: The structure of the envelope protein E1 of two coronaviruses, mouse hepatitis virus strain A59 and infectious bronchitis virus, was analyzed by applying several theoretical methods to their amino acid sequence. The results of these analyses combined with earlier data on the orientation and protease sensitivity of E1 assembled in microsomal membranes lead to a topological model. According to this model, the protein is anchored in the lipid bilayer by three successive membrane-spanning helices present in its N-terminal half whereas the C-terminal part is thought to be associated with the membrane surface; these interactions with the membrane protect almost the complete polypeptide against protease digestion. In addition, it is predicted that the insertion of E1 into the membrane occurs by the recognition of the internal transmembrane region(s) as a signal sequence.


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title: Molecular analysis of the bovine coronavirus S1 gene by direct sequencing of diarrheic fecal specimens.

text: Bovine coronavirus (BCoV) causes severe diarrhea in newborn calves, is associated with winter dysentery in adult cattle and respiratory infections in calves and feedlot cattle. The BCoV S protein plays a fundamental role in viral attachment and entry into the host cell, and is cleaved into two subunits termed S1 (amino terminal) and S2 (carboxy terminal). The present study describes a strategy for the sequencing of the BCoV S1 gene directly from fecal diarrheic specimens that were previously identified as BCoV positive by RT-PCR assay for N gene detection. A consensus sequence of 2681 nucleotides was obtained through direct sequencing of seven overlapping PCR fragments of the S gene. The samples did not undergo cell culture passage prior to PCR amplification and sequencing. The structural analysis was based on the genomic differences between Brazilian strains and other known BCoV from different geographical regions. The phylogenetic analysis of the entire S1 gene showed that the BCoV Brazilian strains were more distant from the Mebus strain (97.8% identity for nucleotides and 96.8% identity for amino acids) and more similar to the BCoV-ENT strain (98.7% for nucleotides and 98.7% for amino acids). Based on the phylogenetic analysis of the hypervariable region of the S1 subunit, these strains clustered with the American (BCoV-ENT, 182NS) and Canadian (BCQ20, BCQ2070, BCQ9, BCQ571, BCQ1523) calf diarrhea and the Canadian winter dysentery (BCQ7373, BCQ2590) strains, but clustered on a separate branch of the Korean and respiratory BCoV strains. The BCoV strains of the present study were not clustered in the same branch of previously published Brazilian strains (AY606193, AY606194). These data agree with the genealogical construction and suggest that at least two different BCoV strains are circulating in Brazil.


title: Neonatal nosocomial respiratory infection with coronavirus: a prospective study in a neonatal intensive care unit.

text: The aim of this prospective study was to evaluate the incidence of viral respiratory infection in hospitalized premature newborn infants and to assess the role of coronaviruses. All hospitalized premature infants with a gestational age less than or equal to 32 weeks were included. Tracheal or nasopharyngal specimens were studied by immunofluorescence for coronaviruses, respiratory syncytial virus, adenoviruses, influenza and parainfluenza viruses. Forty premature infants were included; 13 samples were positive in 10 newborns (coronaviruses n = 10; influenza 1 n = 2; adenovirus n = 1). None was positive at admission. All premature infants infected with coronaviruses had symptoms of bradycardia, apnea, hypoxemia, fever or abdominal distension. Chest X-ray revealed diffuse infiltrates in two cases. However, no significant difference was observed between infected and non-infected premature infants for gestational age, birth weight, duration of ventilation, age at discharge, incidence of apnea or bradycardia. Nosocomial respiratory tract infection with coronaviruses appears to be frequent. The clinical consequences should be evaluated in a larger population.


title: Promoting best practices for control of respiratory infections: collaboration between primary care and public health services.

text: OBJECTIVE To determine the effectiveness of a short-term intervention to promote best practices for control of respiratory infections in primary care physicians' offices. DESIGN Before-after observational study. SETTING Family physicians' offices in Ottawa, Ont. PARTICIPANTS General practitioners and office staff. INTERVENTIONS Four infection-control practices (use of masks, alcohol-based hand gel, and signs, and asking patients to sit at least 1 m apart in the waiting room) were observed, and 2 reported infection-control practices (disinfecting surfaces and use of hand-gel dispensers in examining rooms) were audited before the intervention and 6 weeks after the intervention. MAIN OUTCOME MEASURES Percentage of patients asked to use masks and alcohol-based hand gel, number of relevant signs, and percentage of patients asked to sit at least 1 m away from other patients. Percentage of surfaces disinfected and percentage of physicians using hand-gel dispensers in examining rooms. RESULTS Of 242 practices invited, 53 agreed to participate (22% response rate), and within those practices, 143/151 (95%) physicians participated. Signs regarding respiratory infection control measures increased from 15.4% to 81.1% following the intervention (P < .001). At least 1 patient with cough and fever was given a mask in 17% of practices before the intervention; during the observation period after the intervention, at least 1 patient was given a mask in 66.7% of practices (P < .001). Patients were instructed to use alcohol-based hand gel in 24.5% of practices before the intervention and in 79.2% of practices after it (P < .001). Instruction to sit at least 1 m from others in the waiting area was given in 39.6% of practices before the intervention and in 52.8% of practices following the intervention (P < .001). Before the intervention, the percentage of practices using all 4 audited primary prevention measures was 3.8%; after the intervention, 52.8% of practices were using them (P < .001), demonstrating a 49% increase in adoption of best practices. CONCLUSION A multifaceted intervention by public health nurses successfully promoted best practices for control of respiratory infections in primary care offices. Collaboration between public health services and primary care can promote best practices and warrants further study and development in areas of common interest.


title: US Physicians Trained in Cuba Battle COVID-19 at Home:A Personal Account from the New York City Epicenter.

text: Speaking remotely with US graduates of Havana's Latin American School of Medicine (ELAM), I found them at work on hospital floors, in ICUs and health centers across the United States, putting their professional and personal commitment to the test against COVID-19. Nowhere was that more evident than in New York City, the disease's epicenter, where one grad told me virtually every hospital has at least one MD from the Cuban school, which has provided free 6-year medical training for some 30,000 doctors since the school's founding in 1999. The student body comes primarily from low- and middle-income countries worldwide, but Cuba also provided 200 US students with scholarships. One of them is Dr Joaquín Morante (ELAM Class of 2012), who did his medical residency in internal medicine, followed by fellowships in pulmonary disease and critical care medicine. Triple-licensed in internal medicine, pulmonary and critical care medicine, he is now an attending physician on staff at Jacobi Medical Center in The Bronx, one of New York City's public hospitals, and considered a 'hot spot' due to its COVID-19 caseload. I spoke with him during a break at home in mid-April.Dr Joaquín Morante, ELAM Class of 2012: Pulmonologist, critical care attending physician at Jacobi Medical Center, New York City.


title: Preparing for emerging respiratory pathogens such as SARS-CoV, MERS-CoV, and SARS-CoV-2.

text: Preparing for emerging respiratory pathogens is a fundamental requirement for enhancements of the safeguard in healthcare settings. We are facing an increasing pressure to be prepared more than before. Healthcare organizations should be ready to deal with such emerging infectious disease. Here, we share some points that are essential to be considered while we prepare our institutions to prevent the transmission of emerging respiratory pathogens such as MERS-CoV and the recently emerging pandemic of SARS-CoV-2, the causative agent of COVID-19.


Role of the spike protein in murine coronavirus induced hepatitis: an in vivo study using targeted RNA recombination.


title: Antigenic characterization of a turkey coronavirus identified in poult enteritis- and mortality syndrome-affected turkeys.

text: A turkey coronavirus (TCV [NC95]) was characterized by antigenic comparison with other avian and mammalian coronaviruses using immunofluorescence (FA) and immunoperoxidase (IP) procedures. Based on FA and IP procedures, TCV (NC95) was determined to be antigenically indistinguishable from turkey enteric (bluecomb) coronavirus (TECV). In addition, TCV (NC95) and TECV were found to be closely related to infectious bronchitis virus (IBV); a one-way antigenic relationship was demonstrated. Polyclonal antibodies specific for TECV and IBV reacted strongly against TCV (NC95), as determined by FA procedures. Monoclonal antibodies (MAbs) specific for IBV matrix protein (MAb 919) reacted strongly against TCV (NC95) and TECV as determined by FA and IP procedures; an IBV peplomer protein-specific MAb (MAb 94) did not recognize the two viruses. These studies suggest an identification of TCV (NC95) as a strain of TECV, and provide evidence of a close antigenic relationship between these viruses and IBV.


title: [Analysis of chest X-ray manifestations in 118 patients with severe acute respiratory syndrome].

text: OBJECTIVE To investigate the chest X-ray features and kinetic changes in patients with severe acute respiratory syndrome (SARS). METHODS The appearing time, site, range and imaging features of pulmonary lesions in chest radiograms were observed in 118 patients with clinically confirmed SARS treated in our hospital. Meanwhile, their relation to clinical manifestations was also evaluated. RESULTS Abnormal image appeared in the radiogram in 99.2% of the patients, and it was found in 79.7% of the patients within 4 days after onset of SARS. Lesions in both lungs and multi-lobe pathological changes were noted in 52.2% of the patients. In seven non-survivors, the lesions were included multi-lung lobes, revealing earlier appearance and faster progression compared with the others. CONCLUSION The more serious clinical symptoms and poor prognosis are found in patients with earlier appearance, larger scope and faster progression of SARS lesions in the chest radiogram.


News and Notes.


title: Common ancestry of herpesviruses and tailed DNA bacteriophages.

text: Comparative analysis of capsid protein structures in the eukaryote-infecting herpesviruses (Herpesviridae) and the prokaryote-infecting tailed DNA bacteriophages (Caudovirales) revealed a characteristic fold that is restricted to these two virus lineages and is indicative of common ancestry. This fold not only serves as a major architectural element in capsid stability but also enables the conformational flexibility observed during viral assembly and maturation. On the basis of this and other emerging relationships, it seems increasingly likely that the very diverse collection of extant viruses may have arisen from a relatively small number of primordial progenitors.


title: Activity of 2-(3,4-dichlorophenoxy)-5-nitrobenzonitrile (MDL-860) against picornaviruses in vitro.

text: The newly synthesized compound 2-(3,4-dichlorophenoxy)-5-nitrobenzonitrile (MDL-860) has been found to inhibit picornavirus replication. In multiple growth cycle experiments, 1 microgram of MDL-860 per ml caused a reduction in virus yield of at least 1.0 log10 50% tissue culture infectious doses per 0.2 ml for 8 of 10 enteroviruses and 72 of 90 rhinovirus serotypes. This antiviral activity was dependent on both compound concentration and virus inoculum size. At concentrations that had no toxic effects on cell cultures, MDL-860 did not inhibit cytopathic effect or hemadsorption activity due to coronavirus 229-E, vesicular stomatitis virus, herpes simplex virus type 1, adenovirus, influenza virus A, or parainfluenza virus 1. Compound concentrations up to 25 micrograms/ml did not cause cytopathic effect in short-term cultures of rhesus monkey, WI-38, or HeLa cells; 10 micrograms/ml did not inhibit the replication of HeLa cells. The mechanism of action of MDL-860 has not been defined, although it was not directly virucidal and appeared to inhibit picornaviruses specifically at an early step in the virus-host cell interaction.


title: Secondary structure and function of the 5'-proximal region of the equine arteritis virus RNA genome.

text: Nidoviruses produce an extensive 3'-coterminal nested set of subgenomic mRNAs, which are used to express their structural proteins. In addition, arterivirus and coronavirus mRNAs contain a common 5' leader sequence, derived from the genomic 5' end. The joining of this leader sequence to different segments (mRNA bodies) from the genomic 3'-proximal region presumably involves a unique mechanism of discontinuous minus-strand RNA synthesis. Key elements in this process are the so-called transcription-regulating sequences (TRSs), which determine a base-pairing interaction between sense and antisense viral RNA that is essential for leader-to-body joining. To identify RNA structures in the 5'-proximal region of the equine arteritis virus genome that may be involved in subgenomic mRNA synthesis, a detailed secondary RNA structure model was established using bioinformatics, phylogenetic analysis, and RNA structure probing. According to this structure model, the leader TRS is located in the loop of a prominent hairpin (leader TRS hairpin; LTH). The importance of the LTH was supported by the results of a mutagenesis study using an EAV molecular clone. Besides evidence for a direct role of the LTH in subgenomic RNA synthesis, indications for a role of the LTH region in genome replication and/or translation were obtained. Similar LTH structures could be predicted for the 5'-proximal region of all arterivirus genomes and, interestingly, also for most coronaviruses. Thus, we postulate that the LTH is a key structural element in the discontinuous subgenomic RNA synthesis and is likely critical for leader TRS function.


Covid-19, Cocooning and Vitamin D Intake Requirements.


title: Mouse adenovirus type 1 causes a fatal hemorrhagic encephalomyelitis in adult C57BL/6 but not BALB/c mice.

text: Mouse adenovirus type 1 (MAV-1) produces a lethal disease in newborn or suckling mice characterized by infectious virus and viral lesions in multiple organs. Previous reports of MAV-1 infection of adult mice generally described serologic evidence of infection without morbidity or mortality. However, our current results demonstrate that MAV-1 causes a fatal illness in adult C57BL/6(B6) mice (50% lethal dose, [LD50], 10(3.0) PFU) but not in adult BALB/c mice at all of the doses tested (LD50, > or = 10(5.0) PFU). Adult (BALB/c x B6)F1 mice were intermediately susceptible (LD50, 10(4.5) PFU). Clinically, the sensitive B6 mice showed symptoms of acute central nervous system (CNS) disease, including tremors, seizures, ataxia, and paralysis. Light microscopic examination of CNS tissue from the B6 animals revealed petechial hemorrhages, edema, neovascularization, and mild inflammation in the brain and spinal cord. Analysis by electron microscopy showed evidence of inflammation, such as activated microglia, as well as swollen astrocytic endfeet and perivascular lipid deposition indicative of blood-brain barrier dysfunction. Outside of the CNS, the only significant pathological findings were foci of cytolysis in the splenic white pulp. Assessment of viral replication from multiple tissues was performed by using RNase protection assays with an antisense MAV-1 early region 1a probe. The greatest amounts of viral mRNA in MAV-1-infected B6 animals were located in the brain and spinal cord. Less viral message was detected in the spleen, lungs, and heart. No viral mRNA was detected in BALB/c mouse tissue, with the exception of low levels in the heart. Viral titers of organ tissues were also determined and were concordant with RNase protection findings on the brain and spinal cord but failed to demonstrate significant infectious virus in additional organs. Our experiments demonstrate that MAV-1 has a striking tropism for the CNS that is strain dependent, and this provides an informative in vivo model for the study of adenoviral pathogenesis.


title: Mucosal and systemic immune responses to chimeric fimbriae expressed by Salmonella enterica serovar typhimurium vaccine strains.

text: Recombinant live oral vaccines expressing pathogen-derived antigens offer a unique set of attractive properties. Among these are the simplicity of administration, the capacity to induce mucosal and systemic immunity, and the advantage of permitting genetic manipulation for optimal antigen presentation. In this study, the benefit of having a heterologous antigen expressed on the surface of a live vector rather than intracellularly was evaluated. Accordingly, the immune response of mice immunized with a Salmonella enterica serovar Typhimurium vaccine strain expressing the Escherichia coli 987P fimbrial antigen on its surface (Fas(+)) was compared with the expression in the periplasmic compartment (Fas(-)). Orally immunized BALB/c mice showed that 987P fimbriated Salmonella serovar Typhimurium CS3263 (aroA asd) with pCS151 (fas(+) asd(+)) elicited a significantly higher level of 987P-specific systemic immunoglobulin G (IgG) and mucosal IgA than serovar Typhimurium CS3263 with pCS152 (fasD mutant, asd(+)) expressing 987P periplasmic antigen. Further studies were aimed at determining whether the 987P fimbriae expressed by serovar Typhimurium chi4550 (cya crp asd) could be used as carriers of foreign epitopes. For this, the vaccine strain was genetically engineered to express chimeric fimbriae carrying the transmissible gastroenteritis virus (TGEV) C (379-388) and A (521-531) epitopes of the spike protein inserted into the 987P major fimbrial subunit FasA. BALB/c mice administered orally serovar Typhimurium chi4550 expressing the chimeric fimbriae from the tet promoter in pCS154 (fas(+) asd(+)) produced systemic antibodies against both fimbria and the TGEV C epitope but not against the TGEV A epitope. To improve the immunogenicity of the chimeric fimbriae, the in vivo inducible nirB promoter was inserted into pCS154, upstream of the fas genes, to create pCS155. In comparison with the previously used vaccine, BALB/c mice immunized orally with serovar Typhimurium chi4550/pCS155 demonstrated significantly higher levels of serum IgG and mucosal IgA against 987P fimbria. Moreover, mucosal IgA against the TGEV C epitope was only detected with serovar Typhimurium chi4550/pCS155. The induced antibodies also recognized the epitopes in the context of the full-length TGEV spike protein. Hence, immune responses to heterologous chimeric fimbriae on Salmonella vaccine vectors can be optimized by using promoters known to be activated in vivo.


title: Molecular epidemiology of infectious bronchitis virus in The Netherlands.

text: Twelve Dutch isolates and the M41 strain of infectious bronchitis virus (IBV), a coronavirus of chickens, were characterized by cross-neutralization and T1 finger-printing to elucidate their evolutionary relationship. The T1 fingerprinting showed that the Dutch isolates formed two clusters. The first cluster contained strains H52, H120, D387, V1259, V1385 and V1397; the estimated sequence homology is 99%. Cluster two comprised strains D207, D274, D212, D1466, D3128 and D3896, which have about 95% sequence homology. The M41 virus did not belong to either cluster. The four different serotypes which arose in the late 1970s belonged to cluster two and appeared to be different from the vaccine strains (H52 and H120) used at that time. This indicates that the strains were newly introduced and could have arisen from a common virus. On the other hand, three recently isolated field strains were genetically closely related to the vaccine strains H120 and H52 (cluster one), suggesting that these live vaccine strains themselves could have given rise to these serologically altered field isolates. The data are relevant to the development of new vaccine strategies.


docid: rzijjxde

title: Synergism between allergens and viruses and risk of hospital admission with asthma: case-control study.

text: OBJECTIVE To investigate the importance of sensitisation and exposure to allergens and viral infection in precipitating acute asthma in adults resulting in admission to hospital. DESIGN Case-control study. SETTING Large district general hospital. PARTICIPANTS 60 patients aged 17-50 admitted to hospital over a year with acute asthma, matched with two controls: patients with stable asthma recruited from the outpatient department and patients admitted to hospital with non-respiratory conditions (inpatient controls). MAIN OUTCOME MEASURES Atopic status (skin testing and total and specific IgE), presence of common respiratory viruses and atypical bacteria (polymerase chain reaction), dust samples from homes, and exposure to allergens (enzyme linked immunosorbent assay (ELISA): Der p 1, Fel d 1, Can f 1, and Bla g 2). RESULTS Viruses were detected in 31 of 177 patients. The difference in the frequency of viruses detected between the groups was significant (admitted with asthma 26%, stable asthma 18%, inpatient controls 9%; P=0.04). A significantly higher proportion of patients admitted with asthma (66%) were sensitised and exposed to either mite, cat, or dog allergen than patients with stable asthma (37%) and inpatient controls (15%; P<0.001). Being sensitised and exposed to allergens was an independent associate of the group admitted to hospital (odds ratio 2.3, 95% confidence interval 1.0 to 5.4; P=0.05), whereas the combination of sensitisation, high exposure to one or more allergens, and viral detection considerably increased the risk of being admitted with asthma (8.4, 2.1 to 32.8; P=0.002). CONCLUSIONS Allergens and viruses may act together to exacerbate asthma.


title: Dimensions of subjective well-being and effects of physical activity in Chinese older adults.

text: Subjective well-being (SWB) and its relationship with physical activity have not been systematically investigated in older Chinese people. This study explored these issues using qualitative interviews with a purposive sample of 23 community-dwelling Chinese older adults (age 55-78 y, 12 women); 16 were physically active and 7 physically inactive. Using cross-case analyses, 7 dimensions of SWB emerged: physical, psychological, developmental, material, spiritual, sociopolitical, and social. Although elements of SWB may be shared across cultures, specific distinctions were identified. Active respondents reported the unique contributions of physical activity to the physical, psychological, developmental, and social elements of SWB. The findings suggest that physical activity could enhance the quality of life in Chinese older adults.


title: Minus-strand copies of replicating coronavirus mRNAs contain antileaders.

text: The 5' leader sequence on mRNAs of the porcine transmissible gastroenteritis coronavirus was determined and found to be 90 nucleotides in length. An oligodeoxynucleotide with a sequence from within the leader was used as a probe in Northern analysis on RNA from infected cells, and an antileader (a minus-strand copy of the leader sequence) was shown to be present on all mRNA minus-strand species. RNase protection analysis showed the antileader to be approximately the same length as the leader. The kinetics of antileader appearance was the same as that for the appearance of minus-strand RNA species. This, along with a demonstration that viral mRNAs become packaged, gives further support to the idea that coronavirus mRNAs can undergo replication via subgenomic mRNA-length replicative intermediates, and that input mRNAs from infecting virions may serve as initial templates for their own replication. In this sense, then, coronaviruses behave in part like RNA viruses with segmented genomes.


title: Participation of both host and virus factors in induction of severe acute respiratory syndrome (SARS) in F344 rats infected with SARS coronavirus.

text: To understand the pathogenesis and develop an animal model of severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV), the Frankfurt 1 SARS-CoV isolate was passaged serially in young F344 rats. Young rats were susceptible to SARS-CoV but cleared the virus rapidly within 3 to 5 days of intranasal inoculation. After 10 serial passages, replication and virulence of SARS-CoV were increased in the respiratory tract of young rats without clinical signs. By contrast, adult rats infected with the passaged virus showed respiratory symptoms and severe pathological lesions in the lung. Levels of inflammatory cytokines in sera and lung tissues were significantly higher in adult F344 rats than in young rats. During in vivo passage of SARS-CoV, a single amino acid substitution was introduced within the binding domain of the viral spike protein recognizing angiotensin-converting enzyme 2 (ACE2), which is known as a SARS-CoV receptor. The rat-passaged virus more efficiently infected CHO cells expressing rat ACE2 than did the original isolate. These results strongly indicate that host and virus factors such as advanced age and virus adaptation are critical for the development of SARS in rats.


Association between injections and HIV incidence.


title: Analysis of cytotoxicity induced by proinflammatory cytokines in the human alveolar epithelial cell line A549.

text: Epithelial cell injury under hyperinflammatory conditions is critical in the development of septic acute lung injury (ALI). The aim of the present study is to analyze the cytotoxic effects of a mixture of proinflammatory cytokines in the human alveolar epithelial cell line A549. The cytotoxicity of proinflammatory cytokines were assessed in A549 cells by measuring lactate dehydrogenase released into the culture medium and by crystal violet staining of surviving cells. Activation of the caspase-dependent apoptotic pathway was evaluated by monitoring cleavage of cytokeratin 18 by caspases using enzyme-liked immunosorbent assay (ELISA). To estimate the cytotoxic signaling pathways responsible for epithelial injury, agents with antiinflammatory or antioxidative properties were extensively screened for cytoprotective effects in the inflammation-associated epithelial injury model. The present study revealed that inflammatory cytokines exerted cytotoxicity in A549 cells. A mixture of interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), designated as cytomix, augmented cytotoxicity compared with each individual cytokine. Treatment with glucocorticoid (dexamethasone), tetracycline-derived antiinflammatory antibiotics (minocycline or doxycycline), angiotensin II receptor blockers (losartan or telmisartan), or antioxidants (dimethyl sulfoxide, catalase) attenuated cytomix-induced cytotoxicity, including caspase activation. These results implied that inflammatory cytokines alone could cause alveolar epithelial injury in the pathophysiology of septic ALI. Caspase-dependent apoptosis was speculated to be one mechanism responsible for the cytokine-induced cytotoxicity. Agents with antiinflammatory or antioxidative properties such as glucocorticoid, tetracycline-derived antibiotics, angiotensin II receptor blockers, or direct antioxidants showed substantial effect in attenuating cytokine-induced cytotoxicity and may be candidates for treatment options.


title: Unravelling viral camouflage: approaches to the study and characterization of conformational epitopes.

text: Antibodies are broadly used in clinical and basic research. Many of monoclonal antibodies are successfully adopted for therapeutic and diagnostic targeting of viral pathogens. Efficacy of antiviral neutralizing or protective antibodies depends on their ability to recognize epitopes interfering with viral infection. However, viruses are able to incessantly change their antigenic determinants to escape surveillance of humoral immune system and therefore the successful antiviral therapies require continuous development. Characterization of interactions of antibodies with prevalently conformational viral epitopes is important for understanding antibody mode of action and can help to identify conserved regions that may be exploited in designing new vaccines and virus neutralizing antibodies. In this article, we are reviewing techniques in use for characterization of conformational epitopes of monoclonal antibodies with focus on viruses.


COVID-19 pandemic and rural generalism: the West Coast's rural workforce solution.


title: SARS: retrospective cohort study among German guests of the Hotel 'M', Hong Kong.

text: Hong Kong played a pivotal role in the international spread of the Severe Acute Respiratory Syndrome (SARS): a doctor who spent the night of 21-22 February 2003 at Hotel 'M' was identified as the index case for four national and international clusters of SARS. In parallel to the international collaborative study led by WHO and United States, a retrospective study on the cohort of German persons staying at Hotel 'M' was conducted. The inclusion criteria covered a period from 21 February to 3 March 2003 to allow the detection of cases possibly due to environmental contamination. In the twenty-one German guests traced as having stayed at Hotel "M" during this period, one case of laboratory confirmed SARS was found. The case history suggests that close vicinity to the index patient may have played a role in transmission. In line with findings of environmental investigations in the hotel, environmental contamination should be considered as a possible source of infection.


title: Update: severe acute respiratory syndrome--worldwide and United States, 2003.

text: This report updates reported cases of severe acute respiratory syndrome (SARS) worldwide and in the United States, describes a change in the recommended timing of collection of a convalescent-phase serum specimen to test for antibody to SARS-associated coronavirus (SARS-CoV), and introduces a new case exclusion criterion based on negative SARS-CoV serology. In addition, this report also summarizes changes in travel alerts for Beijing and mainland China, Hong Kong, Toronto, and Taiwan.


title: A code in the protein coding genes.

text: A statistical analysis with 12,288 autocorrelation functions applied in protein (coding) genes of prokaryotes and eukaryotes identifies three subsets of trinucleotides in their three frames: T0 = X0 [symbol: see text] {AAA, TTT} with X0 = {AAC, AAT, ACC, ATC, ATT, CAG, CTC, CTG, GAA, GAC, GAG, GAT, GCC, GGC, GGT, GTA, GTC, GTT, TAC, TTC} in frame 0 (the reading frame established by the ATG start trinucleotide), T1 = X1 [symbol: see text] {CCC} in frame 1 and T2 = X2 [symbol: see text] {GGG} in frame 2 (the frames 1 and 2 being the frame 0 shifted by one and two nucleotides, respectively, to the right). These three subsets are identical in these two gene populations and have five important properties: (i) the property of maximal (20 trinucleotides) circular code for X0 (resp. X1, X2) allowing to retrieve automatically the frame 0 (resp. 1, 2) in any region of the gene without start codon; (ii) the DNA complementarity property C (e.g. C(AAC) = GTT): C(T0) = T0, C(T1) = T2 and C(T2) = T1 allowing the two paired reading frames of a DNA double helix simultaneously to code for amino acids; (iii) the circular permutation property P (e.g. P(AAC) = ACA): P(X0) = X1 and P(X1) = X2 implying that the two subsets X1 and X2 can be deduced from X0; (iv) the rarity property with an occurrence probability of X0 = 6 x 10(-8); and (v) the concatenation properties in favour of an evolutionary code: a high frequency (27.5%) of misplaced trinucleotides in the shifted frames, a maximum (13 nucleotides) length of the minimal window to retrieve automatically the frame and an occurrence of the four types of nucleotides in the three trinucleotide sites. In Discussion, a simulation based on an independent mixing of the trinucleotides of T0 allows to retrieve the two subsets T1 and T2. Then, the identified subsets T0, T1 and T2 replaced in the 2-letter genetic alphabet {R, Y} (R = purine = A or G, Y = pyrimidine = C or T) allow to retrieve the RNY model (N = R or Y) and to explain previous works in the alphabet {R, Y}. Then, these three subsets are related to the genetic code. The trinucleotides of T0 code for 13 amino acids: Ala, Asn, Asp, Gln, Glu, Gly, Ile, Leu, Lys, Phe, Thr, Tyr and Val. Finally, a strong correlation between the usage of the trinucleotides of T0 in protein genes and the amino acid frequencies in proteins is observed as six among seven amino acids not coded by T0, have as expected the lowest frequencies in proteins of both prokaryotes and eukaryotes.


title: Operative Outcomes after Open Abdominal Wall Reconstruction with Retromuscular Mesh Fixation Using Fibrin Glue versus Transfascial Sutures.

text: Ideal fixation techniques have not been fully elucidated at the time of complex open abdominal wall reconstruction (AWR). We compared operative outcomes and quality of life with retromuscular mesh fixation using fibrin glue (FG) versus transfascial sutures (TS). Retrospective review identified complex hernia patients who underwent open AWR with mesh from November 2012 through April 2016. Multivariate analysis examined postoperative outcomes between groups. Quality of life was assessed using the Carolinas Comfort Scale. Seventy-five patients (18 FG vs 57 TS) with mean age (54.3 vs 53.9 years, P = 0.914), body mass index (35.8 vs 34.7 kg/m2, P = 0.623) and American Society of Anesthesiologist score (2.6 vs 2.5, P = 0.617) were reviewed. No differences in wound (P = 0.072) and nonwound (P = 0.639) related complications were noted between groups. Risk of reoperations (P = 0.275) and 30-day readmissions (P = 0.137) were also comparable. The TS group was twelve times more likely to report pain at six-month follow-up compared with FG (12.29 OR, 95 per cent confidence interval 1.26-120.35, P = 0.031). No hernia recurrences were noted in either group at a mean follow-up of 390 ± 330 days. The use of FG to secure mesh in the retromuscular space during complex open AWR may be a safe alternative to penetrating transfascial fixation with potential to reduce chronic pain.


title: Update: mumps outbreak - New York and New Jersey, June 2009-January 2010.

text: State and local health departments, in collaboration with CDC, continue to investigate a mumps outbreak that began in New York in June 2009. The index case occurred in a boy aged 11 years who had returned on June 17 from a trip to the United Kingdom, where approximately 7,400 reports of laboratory-confirmed mumps were received by the Health Protection Agency in 2009. He then attended a New York summer camp for tradition-observant Jewish boys, where he became symptomatic on June 28. Subsequently, other camp attendees and a staff member were reported to have mumps, and transmission continued in multiple locations when the camp attendees returned home. As of January 29, 2010, a total of 1,521 cases had been reported, with onset dates from June 28, 2009, through January 29, 2010, a substantial increase from the 179 cases reported as of October 30, 2009. The outbreak has remained confined primarily to the tradition-observant Jewish community, with <3% of cases occurring among persons outside the community. The largest percentage of cases (61%) has occurred among persons aged 7-18 years, and 76% of the patients are male. Among the patients for whom vaccination status was reported, 88% had received at least 1 dose of mumps-containing vaccine, and 75% had received 2 doses. This is the largest mumps outbreak that has occurred in the United States since 2006. Although mumps vaccination alone was not sufficient to prevent this outbreak, maintaining high measles, mumps, and rubella (MMR) vaccination coverage remains the most effective way to prevent outbreaks and limit their size when they occur.


title: Evaluation of the efficacy and duration of immunity of a canine combination vaccine against virulent parvovirus, infectious canine hepatitis virus, and distemper virus experimental challenges.

text: The results of this study confirmed that dogs vaccinated subcutaneously with a commercially available multivalent vaccine containing modified-live canine distemper virus, canine adenovirus type 2, canine parvovirus type 2b, and canine parainfluenza virus antigens were protected against sequential experimental challenge 55 to 57 months after initial vaccination given at 7 to 8 weeks of age. All 10 vaccinates were protected against clinical diseases and mortality following parvovirus and infectious canine hepatitis experimental infections. All vaccinates were protected against mortality and 90% against clinical disease following distemper challenge. These data support at least a 4-year duration of immunity for these three "core" fractions in the combination vaccine.


title: The potential for emergence of Chagas disease in the United States.

text: To determine the risk for Chagas disease (American trypanosomiasis) in the United States, the characteristics that make the triatomine vector effective and the areas most at risk for transmission were delineated. In addition, the status of Chagas disease awareness among physicians in areas with a potential risk for the disease was determined. A geographical information system (GIS) was used to analyze three triatomine species within the United States known to harbor Trypanosoma cruzi and that exhibit qualities of domesticity. An analysis of the minimum temperature threshold for increased triatomine activity delineates the current population at increased risk, and by incorporating temperature predictions for 2030, the population at risk under a future climate scenario was also delineated. Considering both environmental and social factors, a vignette-based physician survey, based on the results of the GIS analysis, was used to gauge the level of awareness of Chagas disease within the delineated higher risk range. The current area at increased risk for Chagas disease includes much of the southern United States, and the higher risk range is expected to expand into the central United States based upon the 1 degrees C (1.8 degrees F) increase in temperature predicted by the Intergovernmental Panel on Climate Change (IPCC) by the year 2030. Survey results indicate a limited consideration of Chagas disease during differential diagnosis, illustrating that the low number of Chagas disease cases discovered in the United States may be attributable to a lack of disease awareness as opposed to a lack of disease threat. This study combines GIS and survey analyses to evaluate the role that temperature variability and disease awareness among physicians play in the potential emergence of Chagas disease in the United States. This approach indicates that there is a potential for Chagas disease to emerge in the United States.


title: A reverse transcriptase-polymerase chain reaction assay for the diagnosis of turkey coronavirus infection.

text: This study reports on the development of a reverse transcriptase-polymerase chain reaction (RT-PCR) for the specific detection of turkey coronavirus (TCoV). Of the several sets of primers tested, 1 set of primers derived from the P gene and 2 sets derived from the N gene of TCoV could amplify the TCoV genome in the infected samples. The RT-PCR was sensitive and specific for TCoV and did not amplify other avian RNA and DNA viruses tested except the infectious bronchitis virus (IBV). To overcome the problem of IBV amplification, a set of separate primers was designed from the spike protein gene of IBV. The RT-PCR under the same conditions as above could effectively differentiate between TCoV and IBV. The closely related bovine coronavirus and transmissible gastroenteritis virus of pigs were differentiated from TCoV using the same RT-PCR with slight modifications. The results of RT-PCR correlated well with the results of the immunofluorescent test for the same samples tested at the Purdue University Animal Disease Laboratory, West Lafayette, Indiana. The nucleotide sequence and projected amino acid sequence comparison of the P gene of different isolates of TCoV from 5 different states in the United States revealed a close association among the different isolates of TCoV.


title: The effects of temperature, diet, and other factors on development, survivorship, and oviposition of Aethina tumida (Coleoptera: Nitidulidae).

text: Developmental rate and survivorship of small hive beetle, Aethina tumida Murray (Coleoptera: Nitidulidae), life stages were measured across different temperatures (21, 25, 28, 32 and 35 degrees C) and diets, which included natural and artificial pollen, honey, and bee pupae. Temperature affected hatch success, time to hatching, and larval growth. Eggs hatched in 61 h at 21 degrees C but in < 22 h at 35 degrees C. Larvae achieved peak weight in < 8 d at 35 degrees C but needed 17 d at 21 degrees C. Diet had comparatively little effect on larval survivorship or maximum weight, although larvae fed only bee pupae had lower survivorship. Access to soil influenced pupation success. Duration of the life stage spent in the soil, during which pupation occurs, was also affected by temperature: adults emerged after 32.7 d at 21 degrees C but after only 14.8 d at 35 degrees C, albeit with high mortality. Minimum temperature for development was estimated at 13.5 degrees C for eggs, and 10.0 degrees C for larvae and pupae. Temperature influenced adult longevity and oviposition: on a honey and pollen diet average adult lifespan was 92.8 d at 24 degrees C but only 11.6 d at 35 degrees C. Beetles lived longer at 28 degrees C or lower but produced the most eggs per female, regardless of diet, at 32 degrees C. Beetle density influenced fecundity: beetles kept at three pairs per vial laid 6.7 times more eggs per female than those kept as single pairs. Overall, beetles fared best at 28-32 degrees C with mortality of all stages highest at 35 degrees C.


title: Fatal gastroenteritis associated with coronaviruslike particles.

text: The role of human enteric coronaviruses in infantile gastroenteritis is controversial. We detected coronaviruslike particles in the intestinal contents and within the epithelial cells of the ileum in a 15-month-old infant who had postmortem evidence of severe enteritis. Ultrastructural findings consistent with in vivo coronavirus replication in the human small intestine support a causative role for this agent in gastroenteritis.


title: [Risk assessment for emergency events of infectious disease in outlying areas of large-scale activities].

text: OBJECTIVE To identify and assess the potential public health risks of emergency events of infectious disease in the surrounding areas of Hangzhou during the 11th G20 summit, and to assess their impacts on the G20 summit. METHODS The surrounding cities of Hangzhou included Ningbo, Wenzhou, Jiaxing, Huzhou, Shaoxing, Jinhua, Quzhou, Zhoushan, Taizhou and Lishui. Background information on infectious diseases in Zhejiang province was collected, and the brainstorming and expert consultation methods were used to identify the risks. The local risks and the impact of local risks on the G20 summit were assessed. RESULTS The criteria for public health risk was first established. Through the assessments,a total of 27 kinds of infectious diseases in 4 types of public health risks were identified. The impact of these risks on Hangzhou G20 summit was divided into 1 item of high-risk, 12 items of medium risk and 14 items of low risk.According to the results of risk assessment, the recommendations for risk management of respiratory infectious diseases, intestinal infectious diseases, imported infectious diseases like Middle East respiratory syndrome and other infectious diseases were made. With risk management, Middle East respiratory syndrome was not occurred during the G20 summit, and the epidemic situation of other infectious diseases with middle or low risks was almost the same with that of past years. CONCLUSIONS sThe public health risks of Hangzhou G20 summit from sudden infectious diseases in outlying areas are mainly medium and low risks. The recommendations on risk management provide a basis for reducing the adverse consequences of public health risks in the event of an outbreak of infectious diseases, avoiding the impact of various risk factors in the outlying areas on G20 summit.


title: Update: Outbreak of severe acute respiratory syndrome--worldwide, 2003.

text: CDC continues to support the World Health Organization (WHO) in the investigation of a multicountry outbreak of unexplained atypical pneumonia referred to as severe acute respiratory syndrome (SARS). This report includes summaries of the epidemiologic investigations and public health responses in several affected locations where CDC is collaborating with international and national health authorities. This report also describes an unusual cluster of cases associated with a hotel in Hong Kong and identifies the potential etiologic agent of SARS. Epidemiologic and laboratory investigations of SAPS are ongoing.


title: The Genome sequence of the SARS-associated coronavirus.

text: We sequenced the 29,751-base genome of the severe acute respiratory syndrome (SARS)-associated coronavirus known as the Tor2 isolate. The genome sequence reveals that this coronavirus is only moderately related to other known coronaviruses, including two human coronaviruses, HCoV-OC43 and HCoV-229E. Phylogenetic analysis of the predicted viral proteins indicates that the virus does not closely resemble any of the three previously known groups of coronaviruses. The genome sequence will aid in the diagnosis of SARS virus infection in humans and potential animal hosts (using polymerase chain reaction and immunological tests), in the development of antivirals (including neutralizing antibodies), and in the identification of putative epitopes for vaccine development.


title: Primary Umbilical Hernia Repair: A Large-Volume Single-Surgeon Study.

text: There are conflicting views regarding techniques for repair of small umbilical hernias (UHs). Here, we compare the recurrence rate in primary repair with that reported for mesh repair by examining a single surgeon's practice at a large medical center with a comprehensive electronic medical record. A six-year retrospective review of primary UH repairs between January 2012 and December 2017 at Kaiser Permanente Los Angeles Medical Center was undertaken. Patients were identified through a database search of the electronic medical record. The primary endpoint of UH recurrence was examined; median follow-up was 3.4 years. Primary, elective UH repair was performed in 244 patients; 71 per cent of hernias were small (<2 cm). The total number of recurrences was seven (3%). The t test analysis showed significant differences in the average size of hernia defects between those with recurrences (2 cm) and those without (1.4 cm), P < 0.05. Primary repair affords low infection and recurrence rates, comparable to those reported for mesh repair. Our single-surgeon/large-volume study contributes to the evidence that primary UH repair is a safe and durable method, with low risk of recurrence. The use of absorbable monofilament suture, and selection for lower BMI and smaller hernia sizes proved to be effective.


docid: fazckitx

title: Laboratory-acquired severe acute respiratory syndrome.


title: [Electron microscopic virus diagnosis in dogs, cats, calves, swine and foals in the year 1989].

text: During 1989 fecal and gut samples of 598 dogs, 189 cats, 496 calves, 100 pigs and 66 foals with diarrhoea were investigated for virus by electron microscopy. In samples of dogs and cats Parvovirus was detected in 18.5% and 8.5% of the samples, respectively; Coronavirus was found in 14.9% and in 16.4% of the specimens. In samples of calves Coronavirus dominated with a detection rate of 37.5%, followed by Rotavirus with 10.7% and not clearly identifiable particles resembling Coronavirus (4.2%). In 7.1% of the specimens Rotavirus as well as Coronavirus was found. In 33% of specimens from piglets Coronavirus was detected. 10.6% of the faeces from foals contained Coronavirus-like particles. Between 1987 and 1989 the detection rate of Parvovirus in faeces from dogs and cats decreased from 24.2% to 18.6% and from 17.5% to 8.5%. Coronaviruses in calves, dogs and cats increased from 22.9% to 37.5%, from 5.6% to 14.9% and from 8.2% to 16.4% of the samples investigated.


title: Asthma and natural colds. Inflammatory indices in induced sputum: a feasibility study.

text: We examined the feasibility of using induced sputum to evaluate the airway inflammatory response to natural acute respiratory virus infections. We recruited eight asthmatics and nine healthy subjects on Day 4 of a cold. Viral infection was confirmed in six of the asthmatics (influenza A or B) and six of the healthy subjects (influenza A, rhinovirus, adenovirus, respiratory syncytial virus, and coronavirus). In the subjects with confirmed virus infection, five of the asthmatics had an objective exacerbation of asthma during the cold. Their sputum on Day 4 showed a high median total cell count of 19.7 x 10(6) cells/ml with a modest neutrophilia (58. 5%) and high levels of interleukin-8 (IL-8) (16,000 pg/ml), eosinophilic cationic protein (ECP) (1,880 microgram/L) and very high levels of fibrinogen (250 mg/L). In contrast, the proportion (1.3%) and absolute number of eosinophils was low. IL-2 levels were within the normal range, whereas IL-5 and interferon gamma were under the limit of detection of the assays. In the healthy subjects with a confirmed virus infection the sputum findings were qualitatively similar but significantly less prominent. Sputum IL-8 on Day 4 was strongly correlated with neutrophils (rs = 0.8, p < 0.001). This correlation was also significant when each group was analyzed separately. On Day 21 there was a fall in the absolute number of neutrophils and in ECP and fibrinogen levels in both groups. Similar results were found in the two asthmatic and three healthy subjects with a cold of comparable severity but in whom viral infection was not confirmed. We conclude that induced sputum examination can be used to study the effects of natural colds and influenza on the airways of the lungs. The results also suggest that natural colds, on Day 4, cause neutrophilic lower airway inflammation that is greater in asthmatics than in healthy subjects. The greater inflammatory response in asthmatics may be due to the changes associated with trivial eosinophilia or to the different viruses involved.


title: Bedside chest radiography of novel influenza A (H7N9) virus infections and follow-up findings after short-time treatment.

text: BACKGROUND Influenza A (H7N9) virus infections were first observed in China in March 2013. This type virus can cause severe illness and deaths, the situation raises many urgent questions and global public health concerns. Our purpose was to investigate bedside chest radiography findings for patients with novel influenza A (H7N9) virus infections and the followup appearances after short-time treatment. METHODS Eight hospitalized patients infected with the novel influenza A (H7N9) virus were included in our study. All of the patients underwent bedside chest radiography after admission, and all had follow-up bedside chest radiography during their first ten days, using AXIOM Aristos MX and/or AMX-IV portable X-ray units. The exposure dose was generally 90 kV and 5 mAs, and was slightly adjusted according to the weight of the patients. The initial radiography data were evaluated for radiological patterns (ground glass opacity, consolidation, and reticulation), distribution type (focal, multifocal, and diffuse), lung zones involved, and appearance at follow-up while the patients underwent therapy. RESULTS All patients presented with bilateral multiple lung involvement. Two patients had bilateral diffuse lesions, three patients had unilateral diffuse lesions of the right lobe with multifocal lesions of the left lobe, and the remaining three had bilateral multifocal lung lesions. The lesions were present throughout bilateral lung zones in three patients, the whole right lung zone in three patients with additional involvement in the left middle and/or lower lung zone(s), both lower and middle lung zones in one patient, and the right middle and lower in combination with the left lower lung zones in one patient. The most common abnormal radiographic patterns were ground glass opacity (8/8), and consolidation (8/8). In three cases examined by CT we also found the pattern of reticulation in combination with CT images. Four patients had bilateral and four had unilateral pleural effusion. After a short period of treatment the pneumonia in one patient had significantly improved and three cases demonstrated disease progression. In four cases the severity of the pneumonia fluctuated. CONCLUSIONS In patients with influenza A (H7N9) virus infection, the distribution of the lung lesions are extensive, and the disease usually involves both lung zones. The most common imaging findings are a mixture of ground glass opacity and consolidation. Pleural effusion is common. Most cases have a poor short-time treatment response, and seem to have either rapid progressive radiographic deterioration or fluctuating radiographic changes. Chest radiography is helpful for evaluating patients with severe clinical symptoms and for follow-up evaluation.


title: Rapid diagnosis of porcine epidemic diarrhea virus infection by polymerase chain reaction.

text: The diagnosis of porcine epidemic diarrhea virus (PEDV) infection in the laboratory is rather fastidious because of difficulties in virus propagation. The feasibility of virus propagation in vivo is also limited by the handling of a number of samples at the same time. In this study, the detection of PEDV by reverse transcription polymerase chain reaction (RT-PCR) is described. The RT-PCR could detect up to 10(4) TCID50/ml of PEDV and did not show any cross reaction with transmissible gastroenteritis virus or porcine rotavirus. Using this method, the detection of PEDV in experimentally inoculated piglets was possible as early as one day after inoculation. These results suggest that the RT-PCR could be applicable for a rapid diagnosis of PEDV infection.


title: Aerosolization of COVID-19 and Contamination Risks During Respiratory Treatments.

text: Background Aerosolized medications are frequently administered across the health care continuum to acutely ill patients. During viral pandemics, the World Health Organization and the Centers for Disease Control and Prevention advise the application of airborne precautions when performing aerosol-generating medical procedures, such as aerosolized medications. Observations Appropriate personal protective equipment (PPE), including fit-tested particulate respirators should be worn when administering nebulized medications to patients. These PPEs have been in short supply in the US during early phases of the COVID-19 pandemic, which is increasing the risk faced by health care workers (HCWs) who are treating patients using aerosolized medications. Despite taking appropriate precautions, HCWs are becoming infected with COVID-19. This may be related to secondary exposure related to viral longevity in fugitive emissions and viability on fomites. Conclusions We have expanded on non-US public health recommendations to provide guidance to frontline HCWs to enhance collaboration between clinicians, who are often siloed in their clinical practices, and ultimately to protect the federal workforce, which cannot sustain a significant loss of frontline HCWs.


title: Hygromycin B inhibits synthesis of murine coronavirus RNA.

text: The aminoglycoside hygromycin B inhibits the infection of mouse hepatitis virus (MHV) A59 both in vitro and in vivo. In probing the mechanism by which hygromycin B exerts its antiviral effect, we describe here studies which point to inhibition of viral RNA synthesis as the key step in virus replication which is affected by the drug. Cells which are infected with MHV do not take up higher levels of hygromycin B than do uninfected ones. Comparative assays of MHV replication and MHV protein synthesis in the presence of hygromycin B and another aminoglycoside, neomycin, indicate that hygromycin B is the more-effective antiviral agent and that its antiviral activity likely does not involve phosphoinositide-mediated processes such as those inhibited by neomycin.


[Air travel and respiratory diseases].


title: [Emergency surgery during COVID-19 pandemia.]

text: INTRODUCTION The crisis in the SARSCoV-2 coronavirus causing COVID-19 is putting health systems around the world to the test. In a great effort to standardize the management and treatment guidelines, the different health authorities and scientific associations have tried to issue recommendations on how to act in this new and complex scenario. OBJECTIVE: To synthesize the existing evidence and recommendations about urological emergency surgery during the COVID-19 pandemic situation. Furthermore, we propose a general action protocol for these patients. MATERIAL AND METHODS The document is based ont he scarce evidence on SARS / Cov-2 and the experience of the authors in the management of COVID-19 in their institutions, including specialists from Andalusia, Cantabria, Madrid and the Basque Country. A web and PubMed search was performed using the keywords "SARS-CoV-2", "COVID19", "COVID Urology", "COVID19 surgery" and "emergency care". A narrative review of the literature was carried out until April 30, 2020, including only articles and documents written in Spanish and English. After the nominal group technique modified due to the extraordinary restrictions, a first draft was made to unify criteria. Finally, a definitive version was made, agreed by all the authors on May 12, 2020. RESULTS General principles of action are set out, as well as specific recommendations for the most frequent urgent urological procedures. CONCLUSIONS Given the exceptional nature of the situation, there is a lack of evidence regarding the optimal management of the patient with urgent urological pathology. The information is changing, as the epidemiological knowledge of the disease advances. The establishment of multidisciplinary surgical committees that develop and implement action protocols appropriate to the different resources and particular situations of each center is recommended. Likewise, these committees must individually assess each possible urological surgical emergency situation and ensure compliance with protective measures for the patient and other healthcare personnel.


title: Epizootic of viral enteritis in dogs in Thailand.

text: An epizootic of enteritis occurred in dogs in Thailand during 1979. Observations were made on 44 dogs that had clinical signs of enteritis or had a recent history compatible with a clinical diagnosis of enteritis. Eight of the 44 dogs died. Gross and histopathologic examinations performed on these dogs revealed that the lesions were similar to those described for canine viral enteritis. Antigens that agglutinated rhesus macaque RBC were detected in feces from 4 of 20 dogs. Cytopathic effects were observed in canine A-72 cells after their inoculation with fecal suspensions from these 4 dogs and with a fecal suspension from another dog. Cell cultures inoculated with each of the suspensions produced antigens that agglutinated RBC. All hemagglutinating antigens were inhibited in the presence of feline panleukopenia virus antiserum. Using electron microscopy, parvovirus-like virions were observed in a fecal suspension from 2 dogs (1 dog that had antigen that agglutinated rhesus macaque RBC and 1 dog that was negative for feline panleukopenia virus). Canine parvovirus hemagglutination inhibition antibody was detected in sera from 33 of the 40 dogs examined, and canine coronavirus (CV) neutralizing antibody was found in 29 of 30 dogs. Antibody titer increases indicative of recent canine panleukopenia virus (CPV)-like virus and CV infections were observed in paired sera for 2 of 35 and for 5 of 30 of the dogs in Thailand were infected with CPV-like virus and a CV, and these viruses were most likely the cause of the epizootic of viral enteritis.


title: Epidemiology and management of infectious diseases in international adoptees.

text: International adoptees represent a group of children with unique health care needs. Data from published studies, along with the recent experience of the Yale International Adoption Clinic, suggest that the risk of serious infections in adoptees is low, although infections associated with institutionalization still occur commonly. Interpretation of these data must be undertaken with caution, however, since many, if not most, international adoptees are not evaluated in specialty clinics. Thus, prospective studies designed to minimize selection and referral bias are needed in order to accurately define the risk of infectious and noninfectious diseases in all international adoptees.


title: Laboratory-confirmed case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in Malaysia: preparedness and response, April 2014.

text: On 14 April 2014, the first laboratory-confirmed case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection was reported in Malaysia in a man in his mid-fifties, who developed pneumonia with respiratory distress, after returning from a pilgrimage to Saudi Arabia. The case succumbed to his illness three days after admission at a local hospital. The follow-up of 199 close contacts identified through contact tracing and vigilant surveillance did not result in detecting any other confirmed cases of MERS-CoV infection.


docid: pejcuksj

title: Evaluation of a blocking ELISA using monoclonal antibodies for the detection of porcine epidemic diarrhea virus and its antibodies.

text: Two blocking enzyme-linked immunosorbent assays (ELISAs) involving the use of monoclonal antibodies (MAb) as capture and detecting agents and an indirect fluorescence test (IFT) were used for the detection of porcine epidemic diarrhea virus (PEDV) antigen or its antibodies. In the ELISA for viral antigen detection, the blocking step is accomplished by incubation of fecal samples, in duplicate wells, with PEDV-specific positive or negative serum, whereas in the ELISA for antibody detection the blocking step is accomplished by incubation of serum samples with a gut-origin virus suspension. All the methods developed were used to monitor an experimental infection in piglets with the CV-777 strain of PEDV and a natural PED outbreak in a swine fattening unit. The antigen-detection ELISA was able to detect PEDV shedding for a longer time than have previously described methods. The blocking ELISA for antibody detection was able to detect the serum antibody response sooner after PEDV infection than did IFT.


title: RNA-protein interactions in the regulation of coronavirus RNA replication and transcription.

text: Coronavirus, with a 31-kb RNA genome, replicates its own RNA and transcribes subgenomic mRNAs by complex mechanisms. Viral RNA synthesis is regulated by multiple RNA regions, which appear to interact either directly or indirectly. Multiple cellular proteins bind to these regions and may undergo additional protein-protein interactions. These findings suggest that coronavirus RNA synthesis is carried out on a ribonucleoprotein via a mechanism that involves both viral and cellular proteins associated with viral RNA, similar to DNA-dependent RNA transcription. This mode of RNA synthesis may be applicable to most RNA viruses.


title: Comparison of raloxifene and bisphosphonates based on adherence and treatment satisfaction in postmenopausal Asian women.

text: We evaluated adherence with raloxifene therapy compared with daily bisphosphonate in Asian postmenopausal women at increased risk of osteoporotic fractures. In this 12-month observational study conducted in Asia (Hong Kong, Malaysia, Pakistan, Philippines, Singapore, Taiwan), 984 postmenopausal women (aged 55 years or older) were treated with raloxifene 60 mg/day (n = 707; 72%) or daily bisphosphonate (alendronate 10 mg/day; n = 206; 21%, or risedronate 5 mg/day; n = 71; 7%) during their normal course of care. Patients were assessed at baseline, 6, and 12 months. Baseline characteristics (including age, race, education, menopausal status, and baseline fractures) were comparable between the raloxifene and bisphosphonate groups. More women on raloxifene completed the study compared with those on bisphosphonate (50.2% versus 37.5%; P < 0.001). Patients also took raloxifene for a longer period than bisphosphonate (median, 356 versus 348 days; P = 0.011). Compared with those taking bisphosphonate, significantly fewer patients taking raloxifene discontinued the study because of stopping treatment (5.7% versus 10.1%, P = 0.017) or changing treatment (2.8% versus 9.7%, P < 0.001). Inconvenient dosing was reported as a primary reason for discontinuation due to stopping or changing treatment in 19 (6.9%) bisphosphonate patients compared with 0 raloxifene patients. The percentage of patients who had consumed 80% or more of their study medication was similar for raloxifene patients (48-56 weeks; 95.2%) and bisphosphonate patients (48-56 weeks; 93.3%). More raloxifene patients responded that they were satisfied with their medication than bisphosphonate patients at 48-56 weeks (P = 0.002). We concluded that Asian postmenopausal women at increased risk of osteoporotic fractures showed a greater propensity to remain on raloxifene compared with bisphosphonate. The women on raloxifene exhibited lower discontinuation rates and higher treatment satisfaction.


title: ERGIC-53 and traffic in the secretory pathway.

text: The ER-Golgi intermediate compartment (ERGIC) marker ERGIC-53 is a mannose-specific membrane lectin operating as a cargo receptor for the transport of glycoproteins from the ER to the ERGIC. Lack of functional ERGIC-53 leads to a selective defect in secretion of glycoproteins in cultured cells and to hemophilia in humans. Beyond its interest as a transport receptor, ERGIC-53 is an attractive probe for studying numerous aspects of protein trafficking in the secretory pathway, including traffic routes, mechanisms of anterograde and retrograde traffic, retention of proteins in the ER, and the function of the ERGIC. Understanding these fundamental processes of cell biology will be crucial for the elucidation and treatment of many inherited and acquired diseases, such as cystic fibrosis, Alzheimer's disease and viral infections.


title: Laparoscopic management for prenatally diagnosed choledochal cysts.

text: PURPOSE The aim of this study was to validate our laparoscopic management strategy for asymptomatic and symptomatic patients with prenatally diagnosed choledochal cysts (CCs). METHODS Thirteen prenatally diagnosed CC patients from 1997 to 2015 were included. Seven patients (1997-2008) underwent open surgery (OS group), and 6 (2009-2015) underwent laparoscopic surgery (LS group). In the asymptomatic patients, LS was performed when the patients weighed over 5 kg. When the patient had clinical manifestations, early LS was performed irrespective of body weight. A retrospective comparison was conducted between the LS and OS groups in terms of the operative time, blood loss, postoperative fasting period, hospital stay, and intra- and postoperative complications. RESULTS There was no difference between the demographics of both groups. The operative time was significantly longer (380 vs. 288 min) and blood loss was significantly lower (4 vs. 30 mL) in the LS group. Additionally, the postoperative fasting period (3 vs. 6 days) and hospital stay (11 vs. 20 days) were significantly shorter in the LS group. Intraoperative events and early postoperative complications were not encountered in either group. Small bowel obstruction requiring surgery occurred in two patients, 10 and 13 years after OS, respectively. CONCLUSIONS LS is as safe and feasible as OS in small children with prenatally diagnosed CC, although sufficient pediatric laparoscopic expertise is mandatory.


docid: uhixoyfv

title: Coronavirus infection induces H-2 antigen expression on oligodendrocytes and astrocytes.

text: Infection of the central nervous system by mouse hepatitis virus strain A59, a murine neurotropic coronavirus, induces class I major histocompatibility complex antigens on mouse oligodendrocytes and astrocytes, cells that do not normally express these antigens on their surfaces. This induction, which occurs through soluble factors elaborated by infected glial cells, potentially allows immunocytes to interact with the glial cells and may play a critical role in the pathogenesis of virus-induced, immune-mediated demyelination in the central nervous system.


title: [Severe acute respiratory syndrome].

text: Towards the end of 2002 it was the epidemic'outbreak of very severe atypical pneumonia of unknown cause. 32 countries were affected. During 7 months about 8000 cases and 900 fatalities were reported. World Health Organization defined the new disease as severe acute respiratory syndrome (SARS). Thanks to the international investigations the etiologic factor of the disease was quickly identified. New coronavirus was described. It allowed the introduction of new more effective methods of disease' identification. In SARS treatment there are applied antiviral drugs and glicocorticosteroids.


title: Synthesis and processing of the haemagglutinin-esterase glycoprotein of bovine coronavirus encoded in the E3 region of adenovirus.

text: The haemagglutinin-esterase gene (HE) of bovine coronavirus (BCV) encodes a major viral membrane glycoprotein that elicits BCV-neutralizing antibodies. The BCV HE gene was cloned into a human adenovirus serotype 5 (Ad5) transfer vector in place of early transcription region 3, and a helper-independent recombinant virus was constructed by rescue of the transcription unit by homologous in vivo recombination between the vector and Ad5 genomic DNA. The BCV HE polypeptide expressed by this recombinant Ad was characterized in vivo and in vitro. A 65K polypeptide was identified using an anti-BCV antibody in both human (293) and bovine (MDBK) cells infected with the recombinant Ad. In the absence of a reducing agent, migration of the 65K polypeptide was shifted to 130K, indicating that the recombinant HE polypeptide existed in a dimeric form. The HE polypeptide was glycosylated, as demonstrated by labelling with [3H]glucosamine, and was immunoreactive with three distinct groups of conformation-specific anti-HE monoclonal antibodies (MAbs). Cells infected with recombinant Ad expressing BCV HE exhibited both haemadsorption activity and acetylesterase activity. In addition, the anti-HE group A MAbs HC10-5 and KD9-40 inhibited both the haemadsorption activity and esterase activity of the recombinant HE polypeptide, suggesting that the antigenic domain responsible for BCV neutralization may overlap (or is closely associated with) the domain(s) responsible for haemagglutination and/or acetylesterase activities. When mice were inoculated intraperitoneally with live recombinant Ad, a significant level of BCV-neutralizing HE-specific antibody was induced. These results indicate that the recombinant Ad replicates and directs the synthesis of the BCV HE polypeptide in vivo.


title: High-flow cannulas will be required with current COVID-19 crisis, not only mechanical ventilators.

text: COVID-19 is characterized by acute respiratory distress syndrome progression, which ranges from mild to severe. A percentage of critically ill patients will require endotracheal intubation and mechanical ventilation; therefore, Mexican engineers from different places have had the initiative of creating mechanical ventilators. Although artificial ventilator is one of the last resources for the most severely ill patients, there are patients who are on the verge of not meeting the criteria for intubation; if they are directly intubated, the opportunity for them to overcome the severe phase with high concentration supplemental oxygen would be be missed. Intubation per se induces lung damage, increases the risk of superinfection, and the number of days of ICU stay. Furthermore, non-selective use of artificial ventilators decreases the opportunity for patients who require a ventilator to survive and increases institutional care costs of both human and material resources.