title: Identification of 120 kD and 30 kD receptors for human coronavirus OC43 in cell membrane preparations from newborn mouse brain.

text: A biotinylated virus overlay was used to identify a 120kD virus-binding molecule in dissociated newborn mouse brain (nmb) cell suspensions after separation of the proteins by polyacrylamide gel electrophoresis, electroblotting, and blockage of non-specific binding sites. The virus-binding molecule was not detected in adult mouse brain cell suspensions. Mannose- and glucose-rich glycoproteins from nmb cell membranes were selected by ConA-Sepharose (Pharmacia) chromatography. A 30kD virus-binding molecule was eluted by 0.2 M alpha-methyl-D-mannoside. O-linked sialic acid, a receptor component, was identified in the eluate.


title: Convalescence after laparoscopic inguinal hernia repair: a qualitative systematic review.

text: BACKGROUND Duration of convalescence after inguinal hernia repair is of major socio-economic interest and an often reported outcome measure. The primary aim was to perform a critical analysis of duration of convalescence from work and activity and secondary to identify risk factors for unexpected prolonged convalescence after laparoscopic inguinal hernia repair. METHODS A qualitative systematic review was conducted. PubMed, Embase and the Cochrane database were searched for trials reporting convalescence after laparoscopic inguinal hernia repair in the period from January 1990 to January 2016. Furthermore, snowball search was performed in reference lists of identified articles. Randomized controlled trials and prospective comparative or non-comparative trials of high quality were included. Trials with ≥100 patients, >18 years of age and manuscripts in English were included. Scoring systems were used for assessment of quality. RESULTS The literature search identified 1039 papers. Thirty-four trials were included in the final review including 14,273 patients. There was overall a large variation in duration of convalescence. Trials using non-restrictive recommendations of 1-2 days or "as soon as possible to return to all activities" reported overall a shorter duration of convalescence compared with trials not using recommendations for convalescence. Strenuous physical activity at work, strenuous leisure activity and patients with expectations of a prolonged period of convalescence may be risk factors for prolonged convalescence extending more than a few days after laparoscopic inguinal hernia repair. CONCLUSIONS Patients should be recommended a duration of 1-2 days of convalescence after laparoscopic inguinal hernia repair. Short and non-restrictive recommendations may reduce duration of convalescence without increasing risk of pain, complications or recurrence rate.


title: Kansans in the Middle of the Pandemic: Risk Perception, Knowledge, Compliance with Preventive Measures, and Primary Sources of Information about COVID-19.

text: Introduction As we conduct this study, the world is in the grasp of a deadly pandemic. In less than six months since its first diagnosis in Wuhan, China, the COVID-19 infectious disease due to the novel coronavirus has infected over 5,000,000 people and claimed over 350,000 lives. In the United States, most of the cases are in large urban settings along the coasts, but the disease is slowly progressing through the mainland. Kansas, with its particular location in the midwest United States, has seen a relatively small number of cases, but these are increasing. The Kansas government took radical measures to prevent the spread of the disease. According to the Health Beliefs Model, an individual's perception of risk will dictate engagement with preventive behaviors. Knowledge about the disease and preventive measures drive the risk assessment. Knowledge is dependant on the sources of information used. This study explored these metrics in a sample of Kansans living in the times of the COVID-19 pandemic. Methods A combination of snowball samples and random distribution through social media was used to recruit participants to an online survey. The risk and knowledge instrument was developed and validated by WHO Europe. Data collection lasted 96 hours. Results The attitudes and behaviors of Kansans concerning COVID-19 were consistent with its location in an area of the country with a relatively lower incidence of the disease. Participants had good knowledge about the disease and preventive measures and were willing to comply with recommendations from local authorities. Conclusion Localized information sources that cater to the community are often primary, while social media is not a valuable source for information pertinent to COVID-19.


title: Reverse genetics system for the avian coronavirus infectious bronchitis virus.

text: Major advances in the study of the molecular biology of RNA viruses have resulted from the ability to generate and manipulate full-length genomic cDNAs of the viral genomes with the subsequent synthesis of infectious RNA for the generation of recombinant viruses. Coronaviruses have the largest RNA virus genomes and, together with genetic instability of some cDNA sequences in Escherichia coli, this has hampered the generation of a reverse-genetics system for this group of viruses. In this report, we describe the assembly of a full-length cDNA from the positive-sense genomic RNA of the avian coronavirus, infectious bronchitis virus (IBV), an important poultry pathogen. The IBV genomic cDNA was assembled immediately downstream of a T7 RNA polymerase promoter by in vitro ligation and cloned directly into the vaccinia virus genome. Infectious IBV RNA was generated in situ after the transfection of restricted recombinant vaccinia virus DNA into primary chick kidney cells previously infected with a recombinant fowlpox virus expressing T7 RNA polymerase. Recombinant IBV, containing two marker mutations, was recovered from the transfected cells. These results describe a reverse-genetics system for studying the molecular biology of IBV and establish a paradigm for generating genetically defined vaccines for IBV.


title: A review of viral gastroenteritis.

text: PURPOSE OF REVIEW Since Kapakian first identified a virus in the stool of a patient with diarrhoea in 1972, many viruses have been described that cause diarrhoea directly or indirectly. It is now appreciated that viruses are the most common cause of diarrhoeal illness worldwide. Although bacteria and other pathogens cause significant numbers of gastroenteritis, it is the viruses that are dealt with in this review. The viruses responsible will be discussed individually. RECENT FINDINGS Rotavirus remains the leading cause of diarrhoeal disease overall, with the newly designated calicivirus family causing the most outbreaks in the industrialized nations. As diagnostic techniques improve, however, the importance of astrovirus and other previously under-reported pathogens is becoming more apparent and the number of viruses associated with gastroenteritis continues to increase. The emergence of severe acute respiratory syndrome coronavirus, arguably the most important emerging infection of recent years and a cause of significant gastrointestinal disease, is also discussed. SUMMARY No effective treatments have been developed for viral gastroenteritis. Current efforts are targeted at the development of suitable vaccines and the implementation of infection control measures.


title: [Viral etiology of acute respiratory tract infection among pediatric inpatients and outpatients from 2010 to 2012 in Beijing, China].

text: OBJECTIVE Acute respiratory tract infections (ARI) are the leading cause of pediatric morbidity and mortality worldwide, particularly in developing countries. Viruses are the main pathogens of ARI in children. The purpose of the present study was to determine the epidemiologic features of respiratory viruses, including novel viruses, in outpatient and hospitalized children with ARI. METHOD From March 2010 to February 2012, 2066 children with ARI, including 1050 outpatients and 1016 inpatients, were involved in this study. One nasopharyngeal aspirate or throat swab specimen was collected from each patient. Reverse transcription (RT) PCRs were performed to detect common respiratory tract viruses including respiratory syncytial virus (RSV), human rhinovirus (HRV), influenza virus (IFV), parainfluenza virus (PIV) type 1-4, adenovirus (ADV), enterovirus (EV), human coronavirus (HCOV), human metapneumonia virus (HMPV) and human bocavirus (HBOV). RESULT At least one viral pathogen was identified in each of 1274 out of 2066 patients and the overall positive rate was 61.7%. The positive rate in inpatient (69.7%) was higher than that in outpatient (53.9%). The frequencies of detection of various viruses among in- and outpatients were different. RSV was the most prevalent virus detected among hospitalized children, followed by HRV and PIV, whereas IFV was the most frequently identified virus in the outpatient group, followed by ADV and PIV. Simultaneous detection of two or more viruses was found in 377 cases. Coinfection was more frequent in inpatients than in outpatients (30.1% vs. 6.8%, P < 0.001). CONCLUSION Respiratory viruses play an important role in children with ARI, especially in young children. RSV was the most prevalent virus detected among hospitalized children, whereas IFV was the most frequently identified virus in the outpatient group. Viral coinfections are frequently identified, particularly in hospitalized patients. Further studies are required to better understand the impact of coinfections in children with ARI.


title: Toward the development of a plant-based vaccine against reovirus.

text: Transgenic lines of Arabidopsis thaliana producing recombinant TC protein were developed. The S1 gene encoding sigmaC protein of an avian reovirus (ARV) was amplified by reverse-transcription PCR (RT-PCR). The amplified product was cloned into a plant-expression vector, pE1857, with a strong promoter for expression. The resulting construct with the BAR gene cassette for bialaphos selection was designated rpE-sigmaC and was introduced into Agrobacterium tumefaciens by electroporation. Agrobacterium containing the rpE-sigmaC constructs that transform A. thaliana and transgenic plants were selected using bialaphos selection. The presence of S1 transcript in plants and their relative level of expression were determined by real time RT-PCR. Western blot analysis further confirmed the presence of sigmaC protein in the plants. Transgenic lines with high levels of sigmaC protein were selected for immunization experiments using specific-pathogen free chickens. Recombinant sigmaC protein produced in plants induced a variety of immunoglobulin G (IgG) antibody responses in chickens. Recombinant protein administered either subcutaneously or orally in birds showed significant protection against challenge. Results suggested that the recombinant sigmaC protein produced in plants has the potential for large-scale vaccination against ARV in commercial poultry.


title: Comparative pathogenicity of nine US porcine reproductive and respiratory syndrome virus (PRRSV) isolates in a five-week-old cesarean-derived, colostrum-deprived pig model.

text: One hundred forty-six 5-week- old cesarean-derived, colostrum-deprived (CDCD) pigs were inoculated intranasally with 1 of 9 US porcine reproductive and respiratory syndrome virus (PRRSV) isolates. Differences were found in severity of clinical respiratory disease, rectal temperatures (P < or = 0.001), gross lung lesions (P < or = 0.001), and microscopic lung lesions (P < or = 0.05). Gross lung lesions were generally most severe 10 days postinoculation and were distributed primarily in the cranial, middle, and accessory lobes and ventromedial portion of the caudal lung lobes. Mean gross lung lesion scores estimating the percentage of lung affected by pneumonia at 10 days postinoculation ranged from 16.7% +/- 2.8% (mean +/- SEM, n = 10) for isolate ISU-51 to 62.4% +/- 5.7% (n = 10) for isolate ISU-28. Microscopic lung lesions were characterized by hyperplastic and hypertrophied type 2 pneumocytes, septal infiltration by mononuclear cells, and accumulation of necrotic alveolar exudate. Lymph node follicular hyperplasia and focal necrosis was seen with all 9 isolates. This CDCD pig model was useful for demonstration of significant differences in pathogenicity among US PRRSV isolates. This difference in pathogenicity may help explain the variation of severity of clinical disease observed in field outbreaks of porcine reproductive and respiratory syndrome and should provide for meaningful comparison of PRRSV genotypes.


title: Experimental bovine coronavirus in turkey poults and young chickens.

text: The DB2 calf strain of bovine coronavirus (BCV) was used to inoculate 1-day-old specific-pathogen-free (SPF) turkey poults in three trials. In all trials, the birds developed clinical signs of enteritis at 48-72 hr postinoculation. Birds euthanatized at 3, 5, and 7 days postinoculation (DPI) had flaccid, pale intestines with watery contents, and the ceca were markedly enlarged with frothy contents. Coronavirus particles were detected by immune electron microscopy with BCV antibodies from the intestinal contents of birds killed at 3, 5, 7, and 12 DPI. Body weights of inoculated poults killed at 3, 5, and 7 DPI were significantly reduced as compared with controls. Hemagglutinating antibodies were detected in sera of convalescent birds at 12 DPI. However, experimental inoculation of 1-day-old SPF chicks in two trials with the same virus resulted in no clinical signs or macroscopic or microscopic lesions. No coronaviruses were detected from intestinal contents, and there were no significant differences in body weights of inoculated and noninoculated control chicks.


title: Diseases and parasites of red foxes, gray foxes, and coyotes from commercial sources selling to fox-chasing enclosures.

text: Fifty-six red foxes (Vulpes vulpes), 18 gray foxes (Urocyon cinereoargenteus), and 13 coyotes (Canis latrans) obtained by the South Carolina Wildlife and Marine Resources Department during an investigation of suspected illegal wildlife translocation were examined for diseases and parasites. Red foxes and coyotes were confiscated from an animal dealer based in Ohio (USA), and gray foxes were purchased from an animal dealer in Indiana (USA). Emphasis was placed on detection of pathogens representing potential health risks to native wildlife, domestic animals, or humans. All animals were negative for rabies; however, 15 gray foxes were incubating canine distemper at necropsy. Serologic tests disclosed antibodies to canine parvovirus, canine distemper virus, canine adenovirus, canine coronavirus, canine herpesvirus, and canine parainfluenza virus in one or more host species. Twenty-three species of parasites (two protozoans, three trematodes, four cestodes, eleven nematodes, and three arthropods) were found, including species with substantial pathogenic capabilities. Echinococcus multilocularis, a recognized human pathogen not enzootic in the southeastern United States, was found in red foxes. Based on this information, we conclude that the increasingly common practice of wild canid translocation for stocking fox-chasing enclosures poses potential health risks to indigenous wildlife, domestic animals, and humans and, therefore, is biologically hazardous.


title: Antigenic and genomic relationships among turkey and bovine enteric coronaviruses.

text: Antigenic and genomic relationships among tissue culture-adapted turkey enteric coronavirus (TCV) isolates, three strains of avian infectious bronchitis virus (IBV), and mammalian coronaviruses were investigated. Immunoblotting and immunoprecipitation experiments using polyclonal antisera showed that the four major structural proteins of TCV cross-reacted with the four homologous proteins of bovine enteric coronavirus (BCV), the N and M proteins of mouse hepatitis virus serotype 3, and the N protein of IBV. Close antigenic relationships between TCV and BCV were also established by seroneutralization and hemagglutination-inhibition. Of 49 monoclonal antibodies produced against either TCV or BCV, 11 differentiated the two viruses. Five of these monoclonal antibodies had neutralizing activities and were directed to either the peplomeric S (gp200-gp100) or hemagglutinin HE (gp140-gp65) glycoproteins. BCV cDNA probes tested on purified viral preparations and coronavirus-positive (by electron microscopy) fecal samples from diarrheic turkey poults confirmed the relatedness of TCV and BCV. The two viruses produced distinct cytopathic changes in HRT-18 cells in the presence of trypsin, whereas only TCV isolates were able to reproduce the clinical symptoms in turkey poults. Their matrix (M) proteins undergo different glycosylation processes.


Mental Health Act 1983.


title: The effect of disease life history on the evolutionary emergence of novel pathogens.

text: We present a general analytical result for the probability that a newly introduced pathogen will evolve adaptations that allow it to maintain itself within any novel host population, as a function of disease life-history parameters. We demonstrate that this probability of "evolutionary emergence" depends on two key properties of the disease life history: (i) the basic reproduction number and (ii) the expected duration of an infection. These parameters encapsulate all of the relevant information and can be combined in a very simple expression, with estimates for the rates of adaptive mutation, to predict the probability of emergence for any novel pathogen. In general, diseases that initially have a large reproductive number and/or that cause relatively long infections are the most prone to evolutionary adaptation.


title: Prevalence of adolescent idiopathic scoliosis among female school children in Singapore.

text: INTRODUCTION Screening for scoliosis started in Singapore schools in 1982 and is currently being done for both boys and girls, as part of the annual school-based health screening programme in all primary and secondary schools. The screening levels in the current protocol were based on the 1997 prevalence study by Wong et al. In the study, it appeared that there was a significant increase in prevalence rates between 9- and 11-year-old girls (i.e. between Primary 4 and Primary 6) but there was no data on the prevalence rates of scoliosis in 10-year-old girls (Primary 5) and in 12-year-old girls (Secondary 1). In order to decide on whether to make changes to the screening levels, a review was conducted to determine the prevalence of scoliosis among the 10-year-old girls (in Primary 5) and 12-year-old girls (in Secondary 1). MATERIALS AND METHODS A total of 93,626 female students, aged between 9 and 13 years old were screened. The study covered all of the 183 primary schools and only 83 of the 165 secondary schools due to a disruption of health screening in schools during the outbreak of SARS (severe acute respiratory syndrome). In mid-2003, schools in Singapore were closed because Singapore was one of the countries affected by SARS. Scoliosis screening was done for all female students in the Primary 4, 5 and 6 levels as well as in the Secondary 1 and 2 levels. Male students were routinely screened for scoliosis in the Primary 6 and Secondary 2 levels. Scoliosis screening was done by measuring the angle of trunk rotation (ATR) using a scoliometer. All students with ATR >or=5 degrees were referred to the Student Health Centre (SHC) where second-tier screening was done. At SHC, if ATR >or=5 degrees , postero-anterior radiograph of the spine was done. Of the 3186 female students in the primary level, aged between 9 and 13 years old who were referred to SHC for the second-tier screening, 2438 attended, and for secondary students aged between 12 and 13 years old, 1587 out of 1720 students attended. RESULTS The prevalence rates of idiopathic adolescent scoliosis for the 9- to 13-year-old female students were 0.27%, 0.64%, 1.58%, 2.22% and 2.49%, respectively, which showed an increasing trend in the prevalence rates with increasing age. There was a significant increase in the prevalence rates of adolescent idiopathic scoliosis (AIS) in the 10- to 11-year-old females compared to the 9-year-old females (OR, 1.7; 95% CI, 1.1-2.4; P = 0.010). There was also a significant increase in the prevalence rates in the 12- to 13-year-old females (OR, 2.2; 95% CI, 1.4-3.3; P = 0.001). CONCLUSIONS The study showed a significant increase in the prevalence rates of scoliosis in the 10- to 11-year-old female students and again a significant increase in the prevalence rates in the 12- to 13-year-old female students. Since the prevalence rate for the 9-year-old females was quite low (0.27%), and there was a significant increase in the prevalence rates in the 10- to 11-year-old and 12- to 13-year-old females, it was recommended that screening for females be performed every year commencing at 10 years old (Primary 5) until 13 years old (Secondary 2).


title: Plaque assay for titration of bovine enteric coronavirus.

text: The plaquing ability of two isolates of bovine enteric coronavirus (BECV) was studied in HRT18 (human rectal adenocarcinoma) cell monolayers. Both isolates were able to induce plaque formation within 2 to 3 days; plaques appeared as round opalescent areas which remained colourless after neutral red or crystal violet staining. A good correlation was found between the titres as determined either by counting the plaques that were visible to the naked eye before and after neutral red staining, or by enumerating fluorescence or haemadsorption foci.


title: Health effects of subchronic exposure to environmental levels of hardwood smoke.

text: Hardwood smoke is a contributor to both ambient and indoor air pollution. As part of a general health assessment of multiple anthropogenic source emissions conducted by the National Environmental Respiratory Center, a series of health assays was conducted on rodents exposed to environmentally relevant levels of hardwood smoke. This article summarizes the study design and exposures, and reports findings on general indicators of toxicity, bacterial clearance, cardiac function, and carcinogenic potential. Hardwood smoke was generated from an uncertified wood stove, burning wood of mixed oak species. Animals were exposed to clean air (control) or dilutions of whole emissions based on particulate (30, 100, 300, and 1000 micromg/m3). F344 rats, SHR rats, strain A/J mice, and C57BL/6 mice were exposed by whole-body inhalation 6 h/day, 7 days/wk, for either 1 wk or 6 mo. Effects of exposure on general indicators of toxicity, bacterial clearance, cardiac function, and carcinogenic potential were mild. Exposure-related effects included increases in platelets and decreases in blood urea nitrogen and serum alanine aminotransferase. Several other responses met screening criteria for significant exposure effects but were not consistent between genders or exposure times and were not corroborated by related parameters. Pulmonary histopathology revealed very little accumulation of hardwood smoke particulate matter. Parallel studies demonstrated mild exposure effects on bronchoalveolar lavage parameters and in a mouse model of asthma. In summary, the results reported here show few and only modest health hazards from short-term to subchronic exposures to realistic concentrations of hardwood smoke.


title: Early and late CNS-effects of corona virus infection in rats.

text: The mouse hepatitis virus strain JHM was injected intracerebrally into newborn and weanling rats. Three types of diseases were observed: 1. Acute panencephalitis: Almost all suckling rats became moribund within 6 days. Histologically severe panencephalitis with demyelinating foci was noticed; the foci were similar to those found in mice. Virus was easily detectable in the oligodendroglial cells and neurons both by immunofluorescence and electron microscopy. Infectious virus could be isolated. 2. Subacute demyelinating encephalomyelitis (SDE): Three weeks after infection of weanling rats, about 35% of the animals developed paralysis. Neuropathologically, demyelination with a striking predilection for white matter was observed in the brain stem, optic nerve and spinal cord. Virus was detectable by electron microscopy in degenerating oligodendroglial cells only, which corresponded to the results obtained by the immunofluorescent techniques. Infectious virus could be recovered. 3. Chronic progressive paralysis: Inoculated weanling rats without SDE developed 6 to 8 months later a slowly progressing paralysis of the legs. Hydrocephalus and myelomalacia were present. Viral "footprints" could not be detected.


title: Respiratory virus infection of monolayer cultures of human nasal epithelial cells.

text: The effect on nasal epithelial cells in monolayer cultures of infection with rhinovirus, coronavirus 229E, influenza type A, and adenovirus was studied. Fragments (1 x 2 mm) of epithelium with adherent submucosa from nasal polyps, adenoids, or nasal turbinates were cultured in plastic dishes with media containing a serum supplement. Within a week a monolayer of epithelial cells with interspersed ciliated cells surrounded each fragment. Epithelial monolayers were exposed to 10(3) to 10(4) TCID50/ml of each virus; unattached virus was removed after 3 h. Replication of virus was examined by doing viral titrations of the media daily, and ciliated and nonciliated epithelial cells in the monolayer were examined morphologically with an inverted microscope. The peak titer of rhinovirus and coronavirus occurred 24 to 48 h after inoculation, indicating that viral replication was occurring. However, no detectable damage or cytopathic effect (CPE) developed in the monolayer of epithelial cells when compared with that in uninfected control cells. In contrast, infection of epithelial monolayers with influenza or adenovirus resulted in CPE and destruction of the monolayer. The marked difference in the effect of these respiratory viruses on nasal epithelial cells may reflect similar differences in their effect on respiratory tract mucosa in the intact host. If so, the pathogenesis of symptom production during rhinovirus and coronavirus infections must be by mechanisms other than destruction of the nasal lining.


title: The social and political impact of animal diseases.

text: The twenty-first century is characterised by 'epidemiological globalisation' on an unprecedented scale with resulting impacts at the interface of economic, scientific, social and political forces arising from the emergence and re-emergence of animal diseases. Throughout history, animals have served as a source to humankind of food, transportation, medicines, entertainment, clothing, fuel, military advantage and financial security. It is therefore not at all surprising that animal diseases have resulted in significant social and political impacts that have shaped and continue to shape the course of national and international events. The social impacts can be expressed as indirect health consequences or behavioural changes, changes in societal values and changes in social standing and can be felt at the individual, family or community level. The political impact of major disease outbreaks can include loss of public and consumer confidence, resistance to investments in disease surveillance, reluctance to report disease detections in a timely or transparent manner, failure to implement science-based international standards for safe trade (which protect animal, human and ecosystem health) and the removal of government officials. The magnitude of these impacts would support that social and political impacts warrant their inclusion in the consequence assessment of a robust animal disease risk analysis framework.


title: Therapeutic effects of renal denervation on renal failure.

text: Sympathetic nerve activity (SNA) is increased in both patients and experimental animals with renal failure. The kidney is a richly innervated organ and has both efferent and afferent nerves. Renal denervation shows protective effects against renal failure in both animals and humans. The underlying mechanisms include a decrease in blood pressure, a decrease in renal efferent SNA, a decrease in central SNA and sympathetic outflow, and downregulation of the reninangiotensin system. It has been demonstrated that re-innervation occurs within weeks after renal denervation in animals but that no functional re-innervation occurs in humans for over two years after denervation. Renal denervation might not be renal protective in some situations including bile duct ligation-induced renal failure and ischemia/reperfusion-induced acute kidney injury. Catheter-based renal denervation has been applied to patients with both early and end stage renal failure and the published results so far suggest that this procedure is safe and effective at decreasing blood pressure. The effectiveness of renal denervation in improving renal function in patients with renal failure needs to be further investigated.


title: Infants born to mothers with severe acute respiratory syndrome.

text: Severe acute respiratory syndrome (SARS) is a newly discovered infectious disease caused by a novel coronavirus. During the community outbreak in Hong Kong, 5 liveborn infants were born to pregnant women with SARS. A systematic search for perinatal transmission of the SARS-associated coronavirus, including serial reverse transcriptase-polymerase chain reaction assays, viral cultures, and paired serologic titers, failed to detect the virus in any of the infants. In addition, none of the infants developed clinical, radiologic, hematologic, or biochemical evidence suggestive of SARS. One preterm infant developed jejunal perforation and another developed necrotizing enterocolitis with ileal perforation shortly after birth. This case series is the first report to describe the clinical course of the first cohort of liveborn infants born to pregnant women with SARS.


title: Mycobacteriosis, Mycobacterium chelonae, in a captive yellow stingray (Urobatis jamaicensis).

text: An adult yellow stingray (Urobatis jamaicensis) from a touch-tank exhibit developed a large abscess on the dorsal aspect of the calvarium and swollen soft tissue surrounding the left spiracle. A large amount of fluid exudate was drained from the abscess. Mycobacterium chelonae was diagnosed by cytology of the exudate and by polymerase chain reaction and sequencing. The animal was euthanized and disseminated mycobacteriosis was confirmed with histology.


title: Order out of chaos: the self-organization of communication following the anthrax attacks.

text: This article describes 5 communication challenges faced by the author as she managed the communication response by the Centers for Disease Control and Prevention to the anthrax attacks of 2001: communicating uncertainty, selecting credible spokespersons, collaborating with other organizations, satisfying a competitive 24/7 media, and speed. The lessons learned in responding to these challenges led to profound changes in the way communication was organized in the agency. These changes are described within the framework of chaos theory.


title: Politics and the management of public health disasters: reflections on the SARS epidemic in greater China.

text: This paper examines the problems of coordination between and within six jurisdictional players, namely the Hong Kong SAR Government, the Guangdong Province, the Central Authority (PRC), the Taiwanese Government, the Taipei Government and the World Health Organization during the SARS episode from November 2002 until August 2003. We found that the diverging political interests and entrenched administrative practices accounted for the poor coordination between and within these players. The obsession with "political correctness" has severely hampered "rational" decision making among the jurisdictional players. The highly fragmented and compartmentalised intra-jurisdictional public health system means that marshalling resources from health and non-health sectors is difficult.


title: Financial anatomy of biomedical research.

text: CONTEXT Public and private financial support of biomedical research have increased over the past decade. Few comprehensive analyses of the sources and uses of funds are available. This results in inadequate information on which to base investment decisions because not all sources allow equal latitude to explore hypotheses having scientific or clinical importance and creates a barrier to judging the value of research to society. OBJECTIVE To quantify funding trends from 1994 to 2004 of basic, translational, and clinical biomedical research by principal sponsors based in the United States. DESIGN Publicly available data were compiled for the federal, state, and local governments; foundations; charities; universities; and industry. Proprietary (by subscription but openly available) databases were used to supplement public sources. MAIN OUTCOME MEASURES Total actual research spending, growth rates, and type of research with inflation adjustment. RESULTS Biomedical research funding increased from 37.1 billion dollars in 1994 to 94.3 billion dollars in 2003 and doubled when adjusted for inflation. Principal research sponsors in 2003 were industry (57%) and the National Institutes of Health (28%). Relative proportions from all public and private sources did not change. Industry sponsorship of clinical trials increased from 4.0 dollars to 14.2 billion dollars (in real terms) while federal proportions devoted to basic and applied research were unchanged. The United States spent an estimated 5.6% of its total health expenditures on biomedical research, more than any other country, but less than 0.1% for health services research. From an economic perspective, biotechnology and medical device companies were most productive, as measured by new diagnostic and therapeutic devices per dollar of research and development cost. Productivity declined for new pharmaceuticals. CONCLUSIONS Enhancing research productivity and evaluation of benefit are pressing challenges, requiring (1) more effective translation of basic scientific knowledge to clinical application; (2) critical appraisal of rapidly moving scientific areas to guide investment where clinical need is greatest, not only where commercial opportunity is currently perceived; and (3) more specific information about sources and uses of research funds than is generally available to allow informed investment decisions. Responsibility falls on industry, government, and foundations to bring these changes about with a longer-term view of research value.


title: The stability of the duplex between sense and antisense transcription-regulating sequences is a crucial factor in arterivirus subgenomic mRNA synthesis.

text: Subgenomic mRNAs of nidoviruses (arteriviruses and coronaviruses) are composed of a common leader sequence and a "body" part of variable size, which are derived from the 5'- and 3'-proximal part of the genome, respectively. Leader-to-body joining has been proposed to occur during minus-strand RNA synthesis and to involve transfer of the nascent RNA strand from one site in the template to another. This discontinuous step in subgenomic RNA synthesis is guided by short transcription-regulating sequences (TRSs) that are present at both these template sites (leader TRS and body TRS). Sense-antisense base pairing between the leader TRS in the plus strand and the body TRS complement in the minus strand is crucial for strand transfer. Here we show that extending the leader TRS-body TRS duplex beyond its wild-type length dramatically enhanced the subgenomic mRNA synthesis of the arterivirus Equine arteritis virus (EAV). Generally, the relative amount of a subgenomic mRNA correlated with the calculated stability of the corresponding leader TRS-body TRS duplex. In addition, various leader TRS mutations induced the generation of minor subgenomic RNA species that were not detected upon infection with wild-type EAV. The synthesis of these RNA species involved leader-body junction events at sites that bear only limited resemblance to the canonical TRS. However, with the mutant leader TRS, but not with the wild-type leader TRS, these sequences could form a duplex that was stable enough to direct subgenomic RNA synthesis, again demonstrating that the stability of the leader TRS-body TRS duplex is a crucial factor in arterivirus subgenomic mRNA synthesis.


title: [News in the examination of the ciliary activity in the respiratory tract mucosa].

text: Ciliary activity assessment attracts a great interest and has undergone dynamic progress since the last decades. The ciliary function is typically impaired in primary ciliary dyskinesia (PCD). The cilia are mostly examined in vitro, the sample is taken away from the nasal mucosa. Digital videomicroscopy is accessible for the cilia observation in vitro and represents a gold standard. Manual reading using this method is lengthy in comparison with a photomultiplier. Using the photomultiplier, light captured in an optical fibre is analysed automatically by a computer. With technological progress other methods gain ground such as automatical analysis of variance of grey degrees or photomultiplier connected with a scanning confocal microscope. A medium 199 is mostly used for preservation of the functioning cilia. To retain ciliary beat frequency (CBF) it is necessary to use a heated microscope stage. Average physiological CBF value is 11.5 Hz in adult population and 12.8 Hz in children.


title: Neuroinvasion by human respiratory coronaviruses.

text: Human coronaviruses (HCoV) cause common colds but can also infect neural cell cultures. To provide definitive experimental evidence for the neurotropism and neuroinvasion of HCoV and its possible association with multiple sclerosis (MS), we have performed an extensive search and characterization of HCoV RNA in a large panel of human brain autopsy samples. Very stringent reverse transcription-PCR with two primer pairs for both viral strains (229E and OC43), combined with Southern hybridization, was performed on samples from 90 coded donors with various neurological diseases (39 with MS and 26 with other neurological diseases) or normal controls (25 patients). We report that 44% (40 of 90) of donors were positive for 229E and that 23% (21 of 90) were positive for OC43. A statistically significant higher prevalence of OC43 in MS patients (35.9%; 14 of 39) than in controls (13.7%; 7 of 51) was observed. Sequencing of nucleocapsid protein (N) gene amplicons revealed point mutations in OC43, some consistently found in three MS patient brains and one normal control but never observed in laboratory viruses. In situ hybridization confirmed the presence of viral RNA in brain parenchyma, outside blood vessels. The presence of HCoV in human brains is consistent with neuroinvasion by these respiratory pathogens. Further studies are needed to distinguish between opportunistic and disease-associated viral presence in human brains.


title: Enhancement of enteropathogenic Escherichia coli pathogenicity in young turkeys by concurrent turkey coronavirus infection.

text: In a previous study, turkey coronavirus (TCV) and enteropathogenic Escherichia coli (EPEC) were shown to synergistically interact in young turkeys coinfected with these agents. In that study, inapparent or mild disease was observed in turkeys inoculated with only TCV or EPEC, whereas severe growth depression and high mortality were observed in dually inoculated turkeys. The purpose of the present study was to further evaluate the pathogenesis of combined TCV/EPEC infection in young turkeys and determine the role of these agents in the observed synergistic interaction. Experiments were conducted to determine 1) effect of EPEC dose, with and without concurrent TCV infection, and 2) effect of TCV exposure, before and after EPEC exposure, on development of clinical disease. Additionally, the effect of combined infection on TCV and EPEC shedding was determined. No clinical sign of disease and no attaching and effacing (AE) lesions characteristic of EPEC were observed in turkeys inoculated with only EPEC isolate R98/5, even when turkeys were inoculated with 10(10) colony forming units (CFU) EPEC (high dose exposure). Only mild growth depression was observed in turkeys inoculated with only TCV; however, turkeys inoculated with both TCV and 10(4) CFU EPEC (low dose exposure) developed severe disease characterized by high mortality, marked growth depression, and AE lesions. Inoculation of turkeys with TCV 7 days prior to EPEC inoculation produced more severe disease (numerically greater mortality, significantly lower survival probability [P < 0.05], increased frequency of AE lesions) than that observed in turkeys inoculated with EPEC prior to TCV or simultaneously inoculated with these agents. Coinfection of turkeys with TCV and EPEC resulted in significantly increased (P < 0.05) shedding of EPEC, but not TCV, in intestinal contents of turkeys. These findings indicate that TCV infection predisposes young turkeys to secondary EPEC infection and potentiates the expression of EPEC pathogenicity in young turkeys.


title: COVID-19 and gastrointestinal injury: a brief systematic review and data from Bulgaria.

text: In December 2019, a new Coronavirus (SARS-CoV-2) emerged in China, causing the pandemic disease COVID-19. The clinical presentation is variable, but the predominant symptoms are those of the upper respiratory tract. AIM The aim of the current study is to describe the incidence and type of the gastrointestinal injury (GI) in COVID-19, as well as their prognostic value. MATERIALS AND METHODS We conducted a coincidental search on this topic in PubMed, Web of Science and EMBASE. We also followed a group of 31 Bulgarian COVID-19 patients throughout the course of their disease and analyzed their symptoms (catarrhal and other) and outcome. RESULTS The publications concerning our survey followed a total of 1509 COVID-19 patients. In the Bulgarian cohort, only 14 from the 31 patients were laboratory-confirmed COVID-19 cases. Approximately 1/3 of the infected individuals presented with GI. In some patients this was the first, or only, symptom of the disease. It was also indicative of a more severe disease course. CONCLUSION GI may be an important symptom and prognostic factor in COVID-19. Therefore, patients with acute gastrointestinal symptoms must be actively tested for SARS-CoV-2.


title: Identification of the leader-body junctions for the viral subgenomic mRNAs and organization of the simian hemorrhagic fever virus genome: evidence for gene duplication during arterivirus evolution.

text: Simian hemorrhagic fever virus (SHFV) was recently reclassified and assigned to the new virus family Arteriviridae. During replication, arteriviruses produce a 3' coterminal, nested set of subgenomic mRNAs (sgRNAs). These sgRNAs arise by discontinuous transcription, and each contains a 5' leader sequence which is joined to the body of the mRNA through a conserved junction sequence. Only the 5'-most open reading frame (ORF) is believed to be transcribed from each sgRNA. The SHFV genome encodes nine ORFs that are presumed to be expressed from sgRNAs. However, reverse transcription-PCR analysis with leader- and ORF-specific primers identified only eight sgRNA species. The consensus sequence 5'-UCNUUAACC-3' was identified as the junction motif. Our data suggest that sgRNA 2 may be bicistronic, expressing both ORF 2a and ORF 2b. SHFV encodes three more ORFs on its genome than the other arteriviruses. Comparative sequence analysis suggested that SHFV ORFs 2a, 2b, and 3 are related to ORFs 2 through 4 of the other arteriviruses. Evidence which suggests that SHFV ORFs 4 through 6 are related to ORFs 2a through 3 and may have resulted from a recombination event during virus evolution is presented.


title: Strategies for providing mechanical ventilation in a mass casualty incident: distribution versus stockpiling.

text: Federal funding provides state public and private health care systems the ability to build and maintain a reserve supply of ventilators for emergency response to mass casualty incidents. Studying and planning the ventilator reserve capability requires subject-matter expertise, identification of best mechanical-ventilation practices and quality care standards, and contingency planning. Natural disasters such as pandemic influenza, or man-made disasters such as bioterrorism could necessitate field use of numerous mechanical ventilators. This paper discusses the pros and cons of stockpiling ventilators at one site (to be distributed as needed to disaster areas) versus increasing the number of ventilators at all hospitals. Respiratory-device corporations, respiratory professional associations, and respiratory therapists should be involved in the planning and development of respiratory mass casualty response systems.


title: SARS-CoV accessory protein 7a directly interacts with human LFA-1.

text: The SARS-CoV accessory protein 7a is a type I membrane protein with an extracellular domain of 81 amino acid residues. It is described to be expressed during infection and to be a component of the virus particle surface. In this study, we demonstrate that protein 7a binds directly and specifically to human lymphocyte function-associated antigen 1 (LFA-1) on the cell surface of Jurkat cells. The binding is increased upon artificial cell activation with phorbol ester. These observations are confirmed by direct in vitro binding of recombinant protein 7a to the wild type and mutant K287C/K294C I domain showing that the I domain is the 7a binding site in the alpha(L) chain of LFA-1. Consequences of the LFA-1 interaction with 7a are discussed. In particular, our data suggest LFA-1 to be an attachment factor or the receptor for SARS-CoV on human leukocytes.


title: Multiscale, resurgent epidemics in a hierarchical metapopulation model.

text: Although population structure has long been recognized as relevant to the spread of infectious disease, traditional mathematical models have understated the role of nonhomogenous mixing in populations with geographical and social structure. Recently, a wide variety of spatial and network models have been proposed that incorporate various aspects of interaction structure among individuals. However, these more complex models necessarily suffer from limited tractability, rendering general conclusions difficult to draw. In seeking a compromise between parsimony and realism, we introduce a class of metapopulation models in which we assume homogeneous mixing holds within local contexts, and that these contexts are embedded in a nested hierarchy of successively larger domains. We model the movement of individuals between contexts via simple transport parameters and allow diseases to spread stochastically. Our model exhibits some important stylized features of real epidemics, including extreme size variation and temporal heterogeneity, that are difficult to characterize with traditional measures. In particular, our results suggest that when epidemics do occur the basic reproduction number R(0) may bear little relation to their final size. Informed by our model's behavior, we suggest measures for characterizing epidemic thresholds and discuss implications for the control of epidemics.


title: Endoscopic removal of urinary calculi.

text: Despite advances in the prevention and management of urinary calculi, calculus removal remains a common need in small animal practice. In fact, changes in calculus management have increased the percentage of calculi that are difficult to manage medically.1 Endoscopic techniques that reduce the need for calculus removal by traditional laparotomy and cystotomy have been developed. In my experience, most cystic and urethral calculi can be removed by transurethral or laparoscopic-assisted cystoscopy. These techniques decrease trauma to and urine contamination of the abdomen. Endoscopy also improves the ability to examine the urinary system for disease and the presence of more calculi.


title: Chloroquine in controlling biological infections.

text: From the middle of the 17th century, Cinchona tree's bark, which contains quinine, was used as an anti-malarial agent. It wasn't until the midtwentieth century that chloroquine was synthesized, followed by its further derivatives. Chloroquine inhibits protozoan polymerase activity, leading to an increase in heme, which is toxic to Plasmodium. The sensitivity of the protozoan to chloroquine depends on its ability to accumulate the drug in aquatic vacuolas. The medicine is also directly toxic to protozoa of the genus Entamoeba histolytica. The immunomodulatory properties of chloroquine have led to its use in collagen diseases, rheumatic disease, chronic rheumatoid and ankylosing arthritis and autoimmune skin disease. Chloroquine has recently been shown to be effective in controlling infection caused by the new Corona virus 2019- nCov (SARS-CoV-2). The drug inhibits viral infectivity by increasing endosomal pH in cells and blocking virus-cell interference by glycosylating SARS-CoV-2 cell receptors. Chloroquine has been shown to be able to bind sialic acid and gangliosides effectively by blocking the combination of virus S protein with gangliosides, which prevents the infection from starting. The effectiveness of the drug in the first stage of infection by SARS-CoV-2 was confirmed in clinical observations and the drug was included in the developed therapeutic recommendations.


title: Examining the knowledge of and attitudes to pandemic influenza among general practice staff.

text: OBJECTIVE To assess the views, needs and intended behaviour of general practitioners and practice nurses (PNs) regarding pandemic influenza. DESIGN, SETTING AND PARTICIPANTS A postal survey of GPs and PNs in four Divisions of General Practice in New South Wales, selected to represent a diverse sample of practices from inner-city, semi-urban and rural areas. The study was undertaken from 1 February to 1 April 2009. MAIN OUTCOME MEASURES GPs' and PNs' responses to survey statements assessing their awareness and perceived personal risk, intended behaviour in the event of a pandemic, and expectations surrounding antivirals, vaccine and personal and family protection. RESULTS Of 390 general practice staff who were sent the survey, 139 (36%) completed it. Most respondents felt confident that they possessed the necessary knowledge (71.5%, 98/137) and skills (73.7%, 101/137) to provide patient care during an influenza pandemic. Although 38.7% (53/137) stated that they would visit quarantined symptomatic patients, 41.6% (57/137) were unsure. More than half the respondents (53.2%, 74/139) stated that they would require access to vaccination and antivirals for their family as well as themselves before they would attend symptomatic patients at the general practice. CONCLUSION These findings provide evidence of the need to ensure that general practice staff have access to personal and family protection to encourage an adequate response to a pandemic situation.


title: Characterization of the Tupaia rhabdovirus genome reveals a long open reading frame overlapping with P and a novel gene encoding a small hydrophobic protein.

text: Rhabdoviruses are negative-stranded RNA viruses of the order Mononegavirales and have been isolated from vertebrates, insects, and plants. Members of the genus Lyssavirus cause the invariably fatal disease rabies, and a member of the genus Vesiculovirus, Chandipura virus, has recently been associated with acute encephalitis in children. We present here the complete genome sequence and transcription map of a rhabdovirus isolated from cultivated cells of hepatocellular carcinoma tissue from a moribund tree shrew. The negative-strand genome of tupaia rhabdovirus is composed of 11,440 nucleotides and encodes six genes that are separated by one or two intergenic nucleotides. In addition to the typical rhabdovirus genes in the order N-P-M-G-L, a gene encoding a small hydrophobic putative type I transmembrane protein of approximately 11 kDa was identified between the M and G genes, and the corresponding transcript was detected in infected cells. Similar to some Vesiculoviruses and many Paramyxovirinae, the P gene has a second overlapping reading frame that can be accessed by ribosomal choice and encodes a protein of 26 kDa, predicted to be the largest C protein of these virus families. Phylogenetic analyses of the tupaia rhabdovirus N and L genes show that the virus is distantly related to the Vesiculoviruses, Ephemeroviruses, and the recently characterized Flanders virus and Oita virus and further extends the sequence territory occupied by animal rhabdoviruses.


title: Effects of inspiratory muscle training in hemodialysis patients.

text: INTRODUCTION Chronic kidney disease associated with hemodialysis can have a variety of musculoskeletal complications, in addition to repercussions in pulmonary function. OBJECTIVE To evaluate the effects of inspiratory muscle training on inspiratory muscle strength, pulmonary function, and functional capacity in patients with chronic kidney failure undergoing hemodialysis. METHOD Non-controlled clinical trial, comprising 15 individuals diagnosed with chronic kidney failure and undergoing hemodialysis. Maximum inspiratory (PImax) and expiratory (PEmax) pressures were assessed by use of pressure vacuum meter reading. Pulmonary function was assessed by use of spirometry. Functional capacity was assessed by use of walked distance and oxygen consumption obtained in the six-minute walk test (6MWT). For eight weeks, the inspiratory muscle training (IMT) protocol was applied during hemodialysis sessions, with load set to 40% of PImax and weekly frequency of three alternate days. RESULTS A significant increase in the walked distance was observed after training (455.5 ± 98 versus 557.8 ± 121.0; p = 0.003). No statistically significant difference was observed in the other variables when comparing their pre- and posttraining values. CONCLUSION The study showed no statistically significant difference in respiratory muscle strength, pulmonary function, and oxygen consumption. An increase in the walked distance was observed in the 6MWT.


Proteolytic processing of the arterivirus replicase.


Virus-encoded proteinases and proteolytic processing in the Nidovirales.


Chinese scientists must test wild animals to find the host of SARS.


title: VirGen: a comprehensive viral genome resource.

text: VirGen is a comprehensive viral genome resource that organizes the 'sequence space' of viral genomes in a structured fashion. It has been developed with the objective of serving as an annotated and curated database comprising complete genome sequences of viruses, value-added derived data and data mining tools. The current release (v1.1) contains 559 complete genomes in addition to 287 putative genomes of viruses belonging to eight viral families for which the host range includes animals and plants. Viral genomes in VirGen are annotated using sequence-based Bioinformatics approaches. The genomic data is also curated to identify 'alternate names' of viral proteins, where available. VirGen archives the results of comparisons of genomes, proteomes and individual proteins within and between viral species. It is the first resource to provide phylogenetic trees of viral species computed using whole-genome sequence data. The module of predicted B-cell antigenic determinants in VirGen is an attempt to link the genome to its vaccinome. Comparative genome analysis data facilitate the study of genome organization and evolution of viruses, which would have implications in applied research to identify candidates for the design of vaccines and antiviral drugs. VirGen is a relational database and is available at http://bioinfo. ernet.in/virgen/virgen.html.


title: Relationship between occurrence of white diarrhea and changes of properties and components of blood and milk in their dams after parturition in Japanese Black calves.

text: We investigated the diet content and properties of blood and milk in 11 pairs of Japanese Black cows and their calves for the one month following delivery. Four pairs (group A) had been no cases of white diarrhea during the year prior to this study, and 7 pairs (group B) had been a high occurrence of white diarrhea in calves during the same period. Properties of dams' diet in groups A and B before the onset of white diarrhea in calves were as follows: TDN fullness rate 98 +/- 2% vs. 110 +/- 5%, DCP fullness rate 151 +/- 2% vs. 200 +/- 33%, and starch content 5 +/- 2% vs. 14 +/- 3%. Blood and milk samples were collected from cows weekly and at the onset of white diarrhea in calves. No calves in group A had white diarrhea, while 5 out of 7 calves in group B had the diarrhea in this study. All cows were fed mixed hay, but 3 out of 5 cows whose calves had white diarrhea had been additionally given 3.0-3.5 kg of corn-silage a day from 4-5 days before onset. In all cows in the white diarrhea development group, the fat content of milk increased by 2.94 +/- 1.82% at the day of onset in comparison before. Serum TG and BUN, respectively, increased by 3.8 +/- 1.3 mg/dl and 3.7 +/- 2.0 mg/dl. Feeding cows a low-starch diet and additional corn-silage may induce a transient increase in blood TG, BUN and milk fat, which may contribute to the occurrence of white diarrhea in calves.


title: The lessons of SARS in Hong Kong.

text: Severe acute respiratory syndrome (SARS) is a novel coronavirus infection which broke out in Hong Kong in March 2003. Princess Margaret Hospital was designated to manage this new, mysterious and serious disease. Healthcare workers had to work under extremely stressful and often risky conditions to care for patients. Despite manpower and equipment reinforcements, staff infection occurred as a result of bodily exhaustion, working in an unfamiliar environment and lapses in infection control. Patients suffered even more, not only due to physical discomfort, but also because of the fear of isolation and death away from family and friends. Health authorities learnt their lessons in the outbreak and formulated emergency plans for future infectious disease epidemics. The healthcare infrastructure has been examined and upgraded with regard to intensive care capacity, infection control measures, professional training, manpower deployment, staff facilities, and stockpiling of drugs and personal protective equipment.


Planning for pandemic: a new model for governing public health emergencies.


title: [High-efficiency expression of a receptor-binding domain of SARS-CoV spike protein in tobacco chloroplasts].

text: Chloroplast-based expression system is promising for the hyper-expression of plant-derived recombinant therapeutic proteins and vaccines. To verify the feasibility of obtaining high-level expression of the SARS subunit vaccine and to provide a suitable plant-derived vaccine production platform against the severe acute respiratory syndrome coronavirus (SARS-CoV), a 193-amino acid fragment of SARS CoV spike protein receptor-binding domain (RBD), fused with the peptide vector cholera toxin B subunit (CTB), was expressed in tobacco chloroplasts. Codon-optimized CTB-RBD sequence was integrated into the chloroplast genome and homoplasmy was obtained, as confirmed by PCR and Southern blot analysis. Western blot showed expression of the recombinant fusion protein mostly in soluble monomeric form. Quantification of the recombinant fusion protein CTB-RBD was conducted by ELISA analysis from the transplastomic leaves at different developmental stages, attachment positions and time points in a day and the different expression levels of the CTB-RBD were observed with the highest expression of 10.2% total soluble protein obtained from mature transplastomic leaves. Taken together, our results demonstrate the feasibility of highly expressing SARS subunit vaccine RBD, indicating its potential in subsequent development of a plant-derived recombinant subunit vaccine and reagents production for antibody detection in SARS serological tests.


title: Bats as Viral Reservoirs.

text: Bats are hosts of a range of viruses, including ebolaviruses, and many important human viral infections, such as measles and mumps, may have their ancestry traced back to bats. Here, I review viruses of all viral families detected in global bat populations. The viral diversity in bats is substantial, and viruses with all known types of genomic structures and replication strategies have been discovered in bats. However, the discovery of viruses is not geographically even, with some apparently undersampled regions, such as South America. Furthermore, some bat families, including those with global or wide distributions such as Emballonuridae and Miniopteridae, are underrepresented on viral databases. Future studies, including those that address these sampling gaps along with those that develop our understanding of viral-host relationships, are highlighted.


title: Multiple myeloma in cats: variable presentation with different immunoglobulin isotypes in two cats.

text: Multiple myeloma was diagnosed in two cats with monoclonal hyperglobulinemia, proteinuria, and plasma cell proliferations in bone marrow. An immunoglobulin G-producing myeloma occurred in the vertebral bone marrow of one cat, and twice responded to surgical reduction followed by a combination of local irradiation and chemotherapy. The cat's survival time was approximately 2 years. The other myeloma in a cat that presented with hypercalcemia and renal insufficiency involved visceral organs and produced a biclonal peak due to immunoglobulin A dimer formation on serum electrophoresis. This cat's tumor did not respond to chemotherapy.


title: Molecular and cellular mechanisms of DNA vaccines.

text: Although DNA vaccines are already in use for treatment of some animal diseases, they suffer from lower immunogenicity in humans which limits their effectiveness. Thus, recent studies have been focused on strategies to improve the immunogenicity of DNA vaccines. However, there is little known about the molecular and immunological mechanisms by which DNA vaccines work. It has long been the central dogma that DNA vaccine immunogenicity can be attributed to its immunostimulatory CpG motifs acting as 'a built-in adjuvant", which is recognized by Toll-like receptor (TLR) 9, the sole receptor for CpG motifs. Recent research, however, has provided evidence for a new mechanism of action for DNA vaccines. It was reported that the adjuvant effect of plasmid DNA is mediated by its double-stranded structure, which activates TBK1-dependent innate immune signaling pathways in the absence of TLRs. Moreover, TBK1-signaling may delineate direct or indirect (cross) antigen presentation through distinct types of cells in vivo, critical for the induction of antigen-specific CD4(+) or CD8(+) T cells, respectively. This additional information about the mechanism of action of DNA vaccines will lead to improvements in their efficacy and safety.


A 65-year-old woman with acute cough illness and an important engagement.


title: A novel internal open reading frame product expressed from a polycistronic mRNA of porcine epidemic diarrhoea virus may not contribute to virus attenuation.

text: Cell-culture-adapted (ca) porcine epidemic diarrhoea virus (PEDV) contains three internal open reading frames (I ORF) within the nucleocapsid protein gene and lacks the downstream counterpart of porcine transmissible gastroenteritis virus ORF7 or feline infectious peritonitis virus ORF6a. To confirm whether such features also exist in wild-type (wt) PEDV, the 3' 1800 nucleotides of its genome were sequenced and were found to be identical to those of ca virus. The coding potential of I-1 ORF was ascertained by transient expression in Vero cells followed by immunofluorescence using antipeptide sera. The I-1 protein was synthesized as a 12 kDa non-phosphorylated PEDV-specific protein that was not present in detectable amounts in virions. However, a low copy number of I-1 in the virion would suggest it is a structural component. Nevertheless, identical nucleotide sequences and gene expression strategies of attenuated ca virus and its virulent parent, wt PEDV, demonstrate that the 3' 1800 nucleotides or the genes and gene products encoded therein may not contribute to virus attenuation.


title: Assembly of hepatitis B virus envelope proteins onto a lentivirus pseudotype that infects primary human hepatocytes.

text: This study demonstrates that the envelope proteins of hepatitis B virus (HBV) could be incorporated into the lipid membrane of lentivirus pseudotype particles. The assembly procedure was initiated by the transfection of 293T cells with three plasmids: (i) a human immunodeficiency virus (HIV) packaging construct, (ii) a transfer plasmid expressing a reporter gene, and (iii) a plasmid expressing large (L), middle (M), and small (S) HBV envelope proteins. After 2 days, hepatitis B surface antigen and the antigenic forms of L, M, and S were detected at the cell surface by flow cytometry. Also, virus particles that were able to infect cultured primary human hepatocytes (PHH) were released. Under optimal conditions, 50% of PHH could be infected. In addition, the susceptibility of PHH and the resistance of other cell types to the pseudotype particles were similar to those observed for HBV and hepatitis delta virus (HDV), which shares the same L, M, and S. Furthermore, the infection of PHH by the pseudotype was sensitive to known inhibitors of HBV and HDV entry. These findings of specific and efficient infection of hepatocytes could be applicable to liver-specific gene therapy and may help clarify the attachment and entry mechanism used by HBV and HDV.


Robotic-Associating Microwave Liver Ablation with Portal Vein Ligation for Staged Hepatectomy: How I Do It.


title: Community-acquired Pneumonia: A Global Perspective.

text: Community-acquired pneumonia (CAP) is a global disease responsible for a large proportion of deaths and having significant economic cost. As diagnostic tools have increased in sensitivity, our understanding of the etiology of CAP has begun to change with a significant increase in confirmed viral infections and the recognition that multiple pathogens are frequently present. Empiric therapy remains the standard of care and guidelines are mostly based on published data from the United States or Europe. Blindly applying guidelines without any consideration of local etiological differences can lead to a risk of under or overtreatment. Several pathogens are particularly problematic in the setting of CAP in some regions as they are not covered by standard guidelines; in particular, Mycobacterium tuberculosis, Burkholderia pseudomallei, and Acinetobacter baumanii. Overtreatment of patients meeting guideline criteria for healthcare-associated pneumonia is also a problem as this categorization probably only applies to a limited number of areas in the United States. New pathogens are emerging more frequently, as evidenced by severe acute respiratory syndrome, Middle East respiratory syndrome, influenza A H1N1 09, and avian influenza, all of which have global ramifications and good clinicians need to stay informed of evolving threats. There are clearly differences in outcomes from CAP across the globe, but accurately comparing them is difficult given the vast differences in age, comorbidities, and access to healthcare. Improved quality of outcome databases will be a key driver of quality improvement in coming years.


Analysis of passive surveillance data for antimicrobial resistance from cases of neonatal bovine enteritis.


title: Neutralizing antibody decay and lack of contact transmission after inoculation of 3- and 4-day-old piglets with porcine respiratory coronavirus.

text: Ten female neonatal piglets were infected with porcine respiratory coronavirus (PRCV) to measure the decay of a specific neutralizing antibody. By 42 weeks after exposure,1 of the gilts was serologically negative (< 5) for PRCV, and by 48 weeks 2 more gilts were serologically negative. These data demonstrate that young mature gilts can be serologically negative, yet they could have been exposed to PRCV. Sentinel pigs were commingled with the PRCV-infected pigs at 8 weeks after exposure, and no virus transmission occurred.


title: Federal air travel restrictions for public health purposes--United States, June 2007-May 2008.

text: Persons with communicable diseases who travel on commercial aircraft can pose a risk for infection to the traveling public. In June 2007, federal agencies developed a public health Do Not Board (DNB) list, enabling domestic and international public health officials to request that persons with communicable diseases who meet specific criteria and pose a serious threat to the public be restricted from boarding commercial aircraft departing from or arriving in the United States. The public health DNB list is managed by CDC and the U.S. Department of Homeland Security (DHS). To describe the experience with the public health DNB list since its inception, CDC analyzed data from June 2007 to May 2008. This report summarizes the results of that analysis, which indicated that CDC received requests for inclusion of 42 persons on the public health DNB list, all with suspected or confirmed pulmonary tuberculosis (TB). From the requests, 33 (79%) persons were included on the list. The public health DNB list enables public health officials to prevent travel on commercial aircraft by persons who pose a risk for infection to other travelers. State and local health departments in the United States and other countries should be aware of this new public health tool.


title: Increased sensitivity of SARS-coronavirus to a combination of human type I and type II interferons.

text: There is currently an urgent need to identify effective antiviral agents that will prevent and treat severe acute respiratory syndrome coronavirus (SARS-CoV) infection. In this study, we have investigated and compared the antiviral effect of different interferons (IFNs) on SARS-CoV replication in the epithelial kidney monkey Vero cell line. The results showed that SARS-CoV grown in Vero cells is moderately sensitive to IFN-beta and only weakly sensitive to IFN-alpha and IFN-gamma, in comparison to other IFN-sensitive viruses, such as those for encephalomyocarditis, vesicular stomatitis and Newcastle disease. Simultaneous incubation of Vero cells with IFN-beta and IFN-gamma indicated that they may act synergistically against SARS-CoV replication. The IFN-induced MxA protein was detected in the IFN-treated Vero cells. The data, however, suggest that the antiviral activity of IFN against SARS-CoV virus is independent of MxA expression.


title: [Analysis of preventable deaths according to postmortem reports in traumatic deaths].

text: BACKGROUND In this study, we aimed to investigate preventable deaths due to trauma among cases in whom autopsy and postmortem examinations were performed in Diyarbakir Council of Forensic Medicine. METHODS In this study, which was planned as retrospectively descriptive, demographic data, type of injury, cause of injury, locations of injuries, cause of death, and scene of death data were withdrawn through the reports of deaths due to trauma in Diyarbakir Council of Forensic Medicine between 1 January 2008 and 31 December 2008. Medical errors in these deaths and preventable deaths were analyzed with this data. The criteria of American College of Surgeons Committee on Trauma was used for definition-classification of errors and compose of preventability criteria. RESULTS It was concluded that of the 747 cases taken into consideration, 4.15% (n=31) were preventable, 16.20% (n=121) were potentially preventable and 79.65% (n=595) were unpreventable. Suboptimal care in 49.34% (n=75), delay in treatment in 41.45% (n=63), missed diagnosis in 10.53% (n=16), clinical judgment error in 10.53% (n=16), missed medical administration in 7.23% (n=11), and other mistakes in 3.95% (n=6) of the cases were determined. CONCLUSION When the results were compared with the studies performed in the areas in which modern trauma care and trauma centers are located, the preventable death ratio was found high. As a result, it has been determined that development of a modern trauma system and trauma centers have significant roles in decreasing preventable death ratios.


title: In vitro and in vivo characterization of three 68Ga- and 111In-labeled peptides for cholecystokinin receptor imaging.

text: Cholecystokinin (CCK) receptors are overexpressed in several human tumor types, such as medullary thyroid carcinomas and small cell lung cancers. Several ligands for the CCK2 receptor (CCK2R) have been developed for radionuclide targeting of these tumors. In this study, we evaluated whether radiolabeled DOTA-sCCK8 and its stabilized derivative, DOTA-sCCK8[Phe(2)(p-CH2SO3H), Nle(3,6)], are suitable for imaging of CCK2R-positive tumors, using DOTA-MG0 as a reference. In vivo targeting of CCK2R-positive tumors with DOTA-sCCK8, DOTA-sCCK8[Phe(2)(p-CH2SO3H), Nle(3,6)], and DOTA-MG0, labeled with (111)In or (68)Ga, was evaluated in BALB/c nude mice with a subcutaneous A431-CCK2R tumor. Biodistribution studies and single-photon emission computed tomography (SPECT) and positron emission tomography (PET) were performed at 1 hour postinjection. All peptides specifically accreted in the CCK2R-expressing tumors. Both (111)In-DOTA-sCCK8 and (111)In-DOTA-sCCK8[Phe(2)(p-CH2SO3H), Nle(3,6)] showed good tumor retention (4.65% ID/g and 5.44% ID/g, respectively, at 4 hours postinjection). On PET/computed tomographic (CT) and SPECT/CT scans, subcutaneous A431-CCK2R tumors were clearly visualized with low uptake of sCCK8 peptides in the intestines. Whereas radiolabeled DOTA-MG0 showed high kidney uptake (70% ID/g), the sCCK8 peptides showed low uptake in the kidneys. Sulfated CCK8 analogues combined high tumor uptake with low retention in the kidney and are therefore promising tracers for imaging of CCK2R-positive tumors.


title: 2-Mercaptoethanol influences the in vitro function of bovine peripheral blood mononuclear cells.

text: The effects of 2-mercaptoethanol (2-ME) on some in vitro functions of bovine peripheral blood mononuclear cells (PBMC) were examined. It was shown that 2-ME enhanced, in a dose-dependent manner, the production of antibodies to bovine coronavirus. In this test the optimal concentration of 2-ME was 50 microM. This molarity of 2-ME was also optimal for the pokeweed mitogen (PWM)-induced proliferation of PBMC obtained from the 7 cattle tested. Similarly, the spontaneous proliferation of PBMC from 4 out of these cattle was enhanced. Thus, 2-ME evoked an increase (up to 2.5 times) or a decrease (at most 10 times) of the quota between the PWM-induced and the spontaneous proliferation (stimulation index). In general, the presence of 50 microM 2-ME enhanced the in vitro production of interferon by bovine PBMC. On the contrary, the highest proliferative response of PBMC to stimulation with bovine virus diarrhoea virus was achieved in cultures without 2-ME or in cultures with 0.5 or 5 microM 2-ME. Since the effects of 2-ME varied, for different tests as well as for cattle tested, attention should be paid to the use of 2-ME in cultures of bovine PBMC.


Editor's Note: Should We have Seen This (COVID-19 Pandemic) Coming? Addendum, President George W. Bush Did in 2005 and Began Planning.


title: Asbestosis-related years of potential life lost before age 65 years--United States, 1968-2005.

text: Exposure to asbestos fibers can cause asbestosis and other diseases after a latency of 10-40 years from initial exposure to onset of illness. Asbestos still is used in the United States (approximately 2,200 metric tons in 2006) in certain products manufactured domestically. In addition, an undocumented amount of asbestos continues to be imported in products manufactured elsewhere, and a substantial amount of asbestos remains in existing buildings and manufactured products. An estimated 1.3 million construction and general industry workers in the United States potentially are exposed to asbestos each year, mainly from manipulation of asbestos during renovation or demolition activities. Also, although asbestos ore is no longer mined in the United States, some U.S. mine workers might remain at risk for exposure to asbestos contained in other ores. To characterize trends in premature mortality attributed to asbestosis in the United States, CDC analyzed annual underlying cause-of-death data for 1968-2005, the most recent years for which data were available. This report describes the results of that analysis, which indicated that annual years of potential life lost before age 65 years (YPLL) attributed to asbestosis increased 64%, from an average of 146.0 YPLL per year during 1968-1972 to 239.6 per year during 2001-2005 (regression trend for the 5-year moving average, p<0.001), for an overall total of 7,267 YPLL (mean per decedent: 6.2) over the entire period. These results demonstrate that asbestosis-attributable YPLL continue to occur and that efforts to prevent, track, and eliminate asbestosis need to be maintained.


title: Adverse events of lung tissue stapling in thoracic surgery.

text: PURPOSE The use of staplers for thoracic surgery has been regarded as a safe procedure though sometimes adverse events (AEs) of stapling are experienced. The aim of this study is to analyze AEs of lung tissue stapling. METHODS A retrospective multi-institutional review was conducted by 27 institutions of the Central Japan Lung Cancer Surgery Study Group. During the research period, lung tissue stapling was performed 10908 times. RESULTS Total number of AEs related to stapling was 81 (0.74%). Seventy events occurred intraoperatively and 11 events occurred postoperatively. Intraoperative stapling AEs were air leakage (n = 26), laceration of the adjacent lung tissue (n = 23), stapling failure (n = 14), oozing (n = 4), and others (n = 3). The postoperative AEs were prolonged air leakage (n = 9), bleeding from the chest wall (n = 1), and postoperative bleeding (n = 1). Only one case died of acute exacerbation of interstitial pneumonia which was induced after completion lobectomy to cure postoperative bleeding. No relationship was seen between the incidence of AE and cartridge colors or compression types of staplers except the length of cartridges. CONCLUSION Lung tissue stapling in thoracic surgery was safe. The most frequent cause of AEs was stapler-tissue thickness mismatch. The appropriate selection of the cartridge color may decrease the AE incidence of the lung tissue stapling.


title: The spectrum of severe acute respiratory syndrome-associated coronavirus infection.

text: BACKGROUND Whether subclinical or atypical presentations of severe acute respiratory syndrome (SARS) occur and whether clinical judgment is accurate in detecting SARS are unknown. OBJECTIVES To describe the spectrum of SARS coronavirus infection in a large outbreak and to compare diagnoses based on clinical judgment with the SARS coronavirus test. DESIGN Secondary analysis of prospectively collected clinical data and archived serum. SETTING A SARS screening clinic of a university hospital in the New Territories of Hong Kong. PATIENTS 1221 patients attending the clinic between 12 March 2003 and 12 May 2003. MEASUREMENTS SARS coronavirus serology. RESULTS 145 of 553 (26%) patients had serologic evidence of SARS coronavirus infection. Of 910 patients who were managed without hospitalization, only 6 had serologic evidence of SARS. Five of the six patients had normal chest radiographs, and four had symptoms such as myalgia, chills, coughing, and feeling feverish. With the SARS coronavirus serologic test as the gold standard, the clinical diagnosis of probable SARS at hospitalization had a sensitivity of 0.96 (95% CI, 0.91 to 0.98) and a specificity of 0.96 (CI, 0.92 to 0.97). LIMITATIONS Follow-up serologic samples were not obtained from almost half of the patients because they declined further testing. Some people living in the community who were infected but who had minor or no symptoms might not have visited the clinic. CONCLUSIONS There is little evidence of widespread subclinical or mild forms of SARS coronavirus infection. Clinical diagnoses during the outbreak were reasonable and resulted in appropriate triaging.


title: Micro-organisms in outpatient infantile gastroenteritis.

text: This study reports the results of an examination of the stools of 58 infants with gastroenteritis who were seen as outpatients. The stools were examined by routine bacterial culture, and by electron microscopy for virus particles. The stools of a comparable control group of infants who had no gastrointestinal symptoms were also similarly examined. Enteropathogenic Escherichia coli, Salmonella sp., and rotaviruses, as well as other viruses, particularly adenoviruses and coronaviruses, were isolated.


title: SARS precautions.

text: Triage nurses have been urged to ask A&E attenders extra questions to help stop the spread of severe acute respiratory syndrome (SARS).


title: Enhancing the precision of infrared thermodetector for medicine by two-channel measuring technique and mulriple linear interpolation algorithm.

text: The best way to control the spread of Severe Acute Respiratory Syndrome (SARS) is measuring the body temperature precisely, therefore, it is very important to develop a set of high-precision infrared thermodetector for Medicine. The ambient temperature signal and the object temperature signal were collected with two channel AD gates of thermopile infrared sensor unit. The values were calculated by using mulriple linear interpolation algorithm. The precision of the system can reach 0.1°C and the machine can work well in megathermal environment*.


title: Subterfuge and manipulation: type III effector proteins of phytopathogenic bacteria.

text: Diverse gram-negative bacteria deliver effector proteins into the cells of their eukaryotic hosts using the type III secretion system. Collectively, these type III effector proteins function to optimize the host cell environment for bacterial growth. Type III effector proteins are essential for the virulence of Pseudomonas syringae, Xanthomonas spp., Ralstonia solanacearum and Erwinia species. Type III secretion systems are also found in nonpathogenic pseudomonads and in species of symbiotic nitrogen-fixing Rhizobium. We discuss the functions of type III effector proteins of plant-associated bacteria, with an emphasis on pathogens. Plant pathogens tend to carry diverse collections of type III effectors that likely share overlapping functions. Several effectors inhibit host defense responses. The eukaryotic host targets of only a few type III effector proteins are currently known. We also discuss possible mechanisms for diversification of the suite of type III effector proteins carried by a given bacterial strain.


title: Pre-clinical evaluation of a next-generation spray adhesion barrier for multiple site adhesion protection.

text: Intra-abdominal adhesions represent a major cause of postoperative morbidity, including chronic or recurrent pelvic pain and infertility in a significant percent of patients. The SprayShield™ Adhesion Barrier System (Covidien, Waltham, MA) is a next-generation sprayable adhesion barrier to prevent postoperative adhesions. Initially sprayed as a liquid, SprayShield™ solidifies within 2 seconds of contact with tissue through a polyethylene glycol (PEG) ester-Trilysine reaction to form an adherent, internal tissue barrier that protects the underlying tissues for several days after surgery. After tissue begins to heal, the adhesion barrier liquefies via hydrolysis and completely absorbs within 7 days. Safety testing has shown the product to be nongenotoxic, noncytotoxic, nonsensitizing, and nonirritating. SprayShield™ has been shown to adhere well to tissue, with the mechanism of adherence believed to be mainly due to tissue surface mechanical interlocking. In studies that compared SprayShield™ to good surgical technique, virgin hogs were randomized to receive SprayShield™ or good surgical technique (Control). Compared to Controls, SprayShield™ demonstrated a statistically significant reduction in the number of adhesions (46%, p=0.04) and in the area of adhesions (83%, p=0.012) to injured sites. With its ease of application, biocompatibility and adhesion prevention efficacy, SprayShield™ may be an effective next-generation adhesion prevention product for open and laparoscopic abdominopelvic procedures as an adjunct to good surgical technique.


title: Extragenital malignant mixed Mullerian tumor in the incisional hernia - primary carcinosarcoma in the abdominal wall: case report.

text: INTRODUCTION This report presents a primary Mullerian carcinosarcoma localized in the incisional hernia i.e. anterior abdominal wall.There is no data in the literature about this localization of extragenital Mullerian carcinosarcoma. CASE OUTLINE The patient had previous medical history of right-sided ovarian cystadenocarcinoma managed by hysterectomy, bilateral ovariectomy and chemotherapy. An incisional hernia occurred 1 year after the operation and Mullerian carcinosarcoma at the right border of the incisional hernia 16 years later. There was no tumor spreading into the abdominal cavity and pelvis. Full thickness of the abdominal wall resection and coexisting incisional hernia resulted in a large 25x20 cm abdominal wall defect managed by the modified components separation technique and implanting meshes. CONCLUSION Major abdominal wall resection and abdominal wall reconstruction using the modified components separation technique reinforced with meshes could be one of possible solutions in the surgical treatment of primary malignant mixed Mullerian tumor localized in the abdominal wall.


Evolution of a coronavirus during persistent infection in vitro.


title: [Retrospective discriminant analysis of the clinical diagnostic criteria for serious contagious severe acute respiratory syndrome].

text: OBJECTIVE To analyze the clinical diagnostic criteria for serious severe acute respiratory syndrome (SARS) in Guangdong retrospectively discriminant with SARS database, and to screen out the sensitive warning factors in predicting the outcome. METHODS Four hundred and two SARS patients were selected based on the diagnostic criteria for SARS from Ministry of Health, China. Of them, 358 SARS patients were selected as their clinical manifestations conformed to the diagnostic criteria of serious SARS. The study subjects were divided into two groups. One group consisted of the patients with serious SARS (358 patients), and they either underwent invasive or non-invasive mechanical ventilation or died of the disease. The remaining 44 SARS patients constituted the non-serious SARS group. Taking the lowest value of oxygen index (OI) as the main index, the OI was categorized into 3 classes, namely< or =200 mm Hg (1 mm Hg=0.133 kPa) as 1,200-300 mm Hg as 2, and >300 mm Hg as 3. According to this index, the seriousness and the prognosis were analyzed. RESULTS OI less than 300 mm Hg were identified as the unequivocal serious SARS patients, and the mistake judgement rate was 6.800%. Furthermore mortality and complications were compared with Logistic regression, and questionable SARS patients were excluded. The results showed that the patients identified with OI less than 300 mm Hg had worse outcome than the original ones diagnosed with criteria of Ministry of Health. CONCLUSION OI less than 300 mm Hg in patients with ALI meet the diagnostic criteria of serious SARS better, and it can be taken as a prognostic criterion in clinic.


title: High-magnitude, virus-specific CD4 T-cell response in the central nervous system of coronavirus-infected mice.

text: The neurotropic JHM strain of mouse hepatitis virus (MHV) causes acute encephalitis and chronic demyelinating encephalomyelitis in rodents. Previous results indicated that CD8 T cells infiltrating the central nervous system (CNS) were largely antigen specific in both diseases. Herein we show that by 7 days postinoculation, nearly 30% of the CD4 T cells in the acutely infected CNS were MHV specific by using intracellular gamma interferon (IFN-gamma) staining assays. In mice with chronic demyelination, 10 to 15% of the CD4 T cells secreted IFN-gamma in response to MHV-specific peptides. Thus, these results show that infection of the CNS is characterized by a large influx of CD4 T cells specific for MHV and that these cells remain functional, as measured by cytokine secretion, in mice with chronic demyelination.


title: Severe acute respiratory syndrome and the delivery of continuing medical education: case study from Toronto.

text: INTRODUCTION Severe acute respiratory syndrome (SARS) struck Toronto in the spring of 2003, causing many deaths, serious morbidity, forced quarantine of thousands of individuals, and the closure of all provincial hospitals for several weeks. Given the direction by public health authorities to cancel or postpone all continuing medical education (CME) courses, including those sponsored by the University of Toronto Faculty of Medicine, SARS has had a profound effect on the delivery of CME in Toronto and beyond. METHOD Case study design using existing documents and self-report. RESULTS The immediate, specific response of the University of Toronto CME program to SARS is described for the period from March 2003 to September 2003. DISCUSSION During major outbreaks of infectious disease, continuing education providers should maintain regular contact with public health authorities and learners, enact a rational process for postponing or canceling courses, and implement a disaster plan flexible enough to ensure the deliver, of education using technological advances.


title: Atypical extrapulmonary presentations of severe respiratory syncytial virus infection requiring intensive care.

text: The patterns and nature of a four-month epidemic of severe respiratory syncytial virus (RSV)-associated disease were analyzed using presenting, demographic, clinical, and therapeutic data. Of 218 infants with RSV infection admitted to Rainbow Babies and Childrens Hospital, 49 (22.4%), most born prematurely, entered the pediatric intensive care unit (PICU). Fluorescent antibody and/or enzyme-linked immunosorbent assay documented RSV infection. PICU patients underwent airway stabilization; 53.5% were intubated and evaluated for sepsis. Patients with positive bacterial cultures received antibiotics; 18% were given ribavirin. Patterns of infection included hypothermia, septic shock appearance, apnea, pneumonia, and wheezing due to bronchiolitis. The average age difference between patients with hypothermia (23.3 days) and those with pneumonia (11.2 months) was statistically significant. There were no significant differences in average age, gestational age at birth, number intubated, worst pH and PCO2, duration of intensive care, or treatment modalities between infants with bronchopulmonary dysplasia who received ribavirin and those who did not.


title: Differential regulation of Dk and Kk major histocompatibility complex class I proteins on the cell surface after infection of murine cells by pseudorabies virus.

text: After pseudorabies virus (PRV) infection of murine L929 cells, the cell surface expression of major histocompatibility complex (MHC) class I proteins changes such that the total amount of MHC class I molecules remains relatively constant but the levels of the individual alleles Dk and Kk vary. This is an active process involving at least three PRV gene products that act in an allele-specific manner such that cell surface expression of MHC class I Dk is decreased and that of Kk is increased. Our results indicate that an early gene product mediates the overall reduction in Dk protein and a late gene product which is mutant in the attenuated PRV strain Bartha mediates the increase in Kk protein. We provide additional evidence for a third gene product involved in the regulation of the synthesis of both the Dk and Kk proteins. In addition, we show that the early decrease in the Dk protein is not due to a block in synthesis or processing of the complex through the secretory system.


Infectious diseases. Civets back on China's menu.


title: Prospects of RNA interference therapy in respiratory viral diseases: update 2006.

text: Respiratory viruses, such as influenza, parainfluenza and respiratory syncytial virus (RSV), claim millions of lives annually. At present, there is no completely effective vaccine or drug against these highly mutable RNA viruses. Passive antibody therapies for RSV, despite their limited application and staggering cost, enjoy a virtual monopoly in a multibillion-dollar global market. Recently, however, pioneering discoveries have launched RNA interference as a novel, nucleic acid-based therapy against viral pathogens. Specifically, small interfering RNAs (siRNAs) offered protection against respiratory syncytial virus, parainfluenza and influenza. siRNA against RSV has entered Phase I clinical trials in humans, and preliminary reports are promising. If appropriately formulated for improved specificity, delivery and pharmacokinetics, siRNAs may indeed become effective antivirals in the clinics of the future. This paper provides an overview of the prospects and hurdles facing the antiviral siRNA drugs, with special emphasis on RSV.


title: Caspase-mediated cleavage of the feline calicivirus capsid protein.

text: Feline calicivirus (FCV) is responsible for an acute upper respiratory tract disease in cats. The FCV capsid protein is synthesized as a precursor (76 kDa) that is post-translationally processed into the mature 62 kDa capsid protein by removal of the N-terminal 124 amino acids. Our previous studies have also detected a 40 kDa protein, related to the FCV capsid protein, produced during infection. Here we demonstrate that cleavage of the FCV capsid protein, during infection of cells in culture, was prevented by caspase inhibitors. In addition, caspase-2, -3 and -7 were activated during FCV infection, as shown by pro-form processing, an increase in N-acetyl-Asp-Glu-Val-Asp-7-amido-4-trifluoromethylcoumarin cleavage activity and in situ poly(ADP-ribose) polymerase cleavage. Caspase activation coincided with the induction of apoptosis and capsid cleavage to the 40 kDa fragment. An in vitro cleavage assay, using recombinant human caspases and in vitro-derived FCV capsid protein, revealed that caspase-2, and to a lesser extent caspase-6, cleaved the capsid protein to generate a 40 kDa fragment. Taken together, these results suggest that FCV triggers apoptosis within infected cells and that caspase-induced capsid cleavage occurs concomitantly with apoptosis. The possible role of capsid cleavage in the pathogenesis of FCV infection is discussed.


title: A new vision for distance learning and continuing medical education.

text: Increasing demands on continuing medical education (CME) are taking place at a time of significant developments in educational thinking and new learning technologies. Such developments allow today's CME providers to better meet the CRISIS criteria for effective continuing education: convenience, relevance, individualization, self-assessment, independent learning, and a systematic approach. The International Virtual Medical School (IVIMEDS) provides a case study that illustrates how rapid growth of the Internet and e-learning can alter undergraduate education and has the potential to alter the nature of CME. Key components are a bank of reusable learning objects, a virtual practice with virtual patients, a learning-outcomes framework, and self-assessment instruments. Learning is facilitated by a curriculum map, guided-learning resources, "ask-the-expert" opportunities, and collaborative or peer-to-peer learning. The educational philosophy is "just-for-you" learning (learning customized to the content, educational strategy, and distribution needs of the individual physician) and "just-in-time" learning (learning resources available to physicians when they are required). Implications of the new learning technologies are profound. E-learning provides a bridge between the cutting edge of education and training and outdated procedures embedded in institutions and professional organizations. There are important implications, too, for globalization in medical education, for multiprofessional education, and for the continuum of education from undergraduate to postgraduate and continuing education.


title: [The human gastroenteritis virus in the Quebec region (1986-1991). Identification by electronic microscopy].

text: Between 1986 and 1991, 251 fecal samples were examined. Viruses were found in 48% of stools, namely adenoviruses, astroviruses, caliciviruses, coronaviruses, rotaviruses, and particles reassembling the Norwalk agent (74% of positive cases). All morphological types of viruses normally associated with human gastroenteritis are present in Quebec, its vicinity, and in the east of the Province. The interpretation of specimens is complicated by the presence of a wide variety of biological structures including bacteriophages. Electron microscopy is the method of choice for identification of the whole range of gastroenteritis viruses.


title: An Outbreak of Human Coronavirus OC43 Infection and Serological Cross-reactivity with SARS Coronavirus.

text: BACKGROUND In summer 2003, a respiratory outbreak was investigated in British Columbia, during which nucleic acid tests and serology unexpectedly indicated reactivity for severe acute respiratory syndrome coronavirus (SARS-CoV). METHODS Cases at a care facility were epidemiologically characterized and sequentially investigated for conventional agents of respiratory infection, SARS-CoV and other human CoVs. Serological cross-reactivity between SARS-CoV and human CoV-OC43 (HCoV-OC43) was investigated by peptide spot assay. RESULTS Ninety-five of 142 residents (67%) and 53 of 160 staff members (33%) experienced symptoms of respiratory infection. Symptomatic residents experienced cough (66%), fever (21%) and pneumonia (12%). Eight residents died, six with pneumonia. No staff members developed pneumonia. Findings on reverse transcriptase-polymerase chain reaction assays for SARS-CoV at a national reference laboratory were suspected to represent false positives, but this was confounded by concurrent identification of antibody to N protein on serology. Subsequent testing by reverse transcriptase-polymerase chain reaction confirmed HCoV-OC43 infection. Convalescent serology ruled out SARS. Notably, sera demonstrated cross-reactivity against nucleocapsid peptide sequences common to HCoV-OC43 and SARS-CoV. CONCLUSIONS These findings underscore the virulence of human CoV-OC43 in elderly populations and confirm that cross-reactivity to antibody against nucleocapsid proteins from these viruses must be considered when interpreting serological tests for SARS-CoV.