title: Association between infection of the respiratory tract attributable to bovine coronavirus and health and growth performance of cattle in feedlots.

text: OBJECTIVE To determine the association between respiratory tract infection with bovine coronavirus (BCV), treatment for respiratory tract disease, pulmonary lesions at slaughter, and average daily gain in cattle in feedlots. ANIMALS 837 calves in feedlots in Ohio and Texas. PROCEDURE Nasal swab specimens were obtained from cattle at arrival in a feedlot (day 0) and at various times during the initial 28 days after arrival. Specimens were tested for BCV, using an antigen-capture ELISA. Serum samples were obtained at arrival and again 28 days after arrival and tested for antibodies to BCV, using an antibody-detection ELISA. Information was collected regarding treatment for cattle with respiratory tract disease and average daily gain during the feeding period. Pulmonary lesions were evaluated at slaughter. RESULTS Cattle shedding BCV from the nasal cavity and developing an antibody response against BCV were 1.6 times more likely to require treatment for respiratory tract disease than cattle that did not shed the virus or develop an immune response against BCV. Additionally, cattle that shed BCV from the nasal cavity were 2.2 times more likely to have pulmonary lesions at slaughter than cattle that did not shed the virus. The BCV shedding or seroconversion status did not affect average daily gain. CONCLUSIONS AND CLINICAL RELEVANCE Bovine coronavirus infects feedlot cattle and is associated with an increased risk for cattle developing respiratory tract disease and pulmonary lesions. Development of appropriate control measures could help reduce the incidence of respiratory tract disease.


title: Occupational fatalities during trenching and excavation work--United States, 1992-2001.

text: Fatalities associated with trench collapses and other excavation hazards continue to occur despite Occupational Safety and Health Administration (OSHA) standards that specify safe work practices to reduce such hazards to workers. To assess the hazards of trenching and excavation work in the United States, CDC reviewed data from national occupational fatality records and investigative reports of fatal injuries. This report summarizes the results of that analysis, which indicated that 76% of the deaths were caused by cave-ins and 47% of the deaths occurred among employees of companies with < or =10 workers. Employers can reduce the risk for future deaths by adhering to OSHA standards and by using education and training resources on safe excavation and trenching practices offered by the National Institute for Occupational Safety and Health (NIOSH), OSHA, and labor and trade organizations.


Some drugs for COVID-19.


title: Amino acid substitutions in the s2 region enhance severe acute respiratory syndrome coronavirus infectivity in rat angiotensin-converting enzyme 2-expressing cells.

text: To clarify the molecular basis of severe acute respiratory syndrome coronavirus (SARS-CoV) adaptation to different host species, we serially passaged SARS-CoV in rat angiotensin-converting enzyme 2 (ACE2)-expressing cells. After 15 passages, the virus (Rat-P15) came to replicate effectively in rat ACE2-expressing cells. Two amino acid substitutions in the S2 region were found on the Rat-P15 S gene. Analyses of the infectivity of the pseudotype-bearing S protein indicated that the two substitutions in the S2 region, especially the S950F substitution, were responsible for efficient infection. Therefore, virus adaptation to different host species can be induced by amino acid substitutions in the S2 region.


title: Infection in renal transplant recipients.

text: Renal transplant recipients are susceptible to infection by a wide array of pathogens. Impaired inflammatory responses due to immunosuppressive therapies suppress clinical and radiologic findings engendered by microbial invasion. As a result, patients are often minimally symptomatic and evaluation and diagnosis are delayed. Specific microbiologic diagnosis is essential both for the optimization of antimicrobial therapy and to avoid unnecessary drug toxicities. Differential diagnosis is guided by knowledge of organisms commonly involved in infection in immunocompromised hosts and understanding of the limitations of prophylactic strategies. The risk of infection in the organ transplant recipient is determined by the interaction between the individual's epidemiologic exposures and net state of immunosuppression. Epidemiology includes environmental exposures in the community and hospital, organisms derived from donor tissues and latent infections activated in the host during immune suppression. The net state of immune suppression is determined by the interaction of all factors contributing to infectious risk. Routine antimicrobial prophylaxis is aimed at common infections and unique risk factors in individual patient groups. This includes trimethoprim-sulfamethoxazole (for Pneumocystis, Toxoplasma, most Nocardia and Listeria, common urinary pathogens), perioperative (eg, anti-fungal prophylaxis for pancreas transplants), or antiviral (for herpesviruses in high risk recipients).


title: The link between thyroid autoimmunity (antithyroid peroxidase autoantibodies) with anxiety and mood disorders in the community: a field of interest for public health in the future.

text: BACKGROUND To evaluate the association between mood and anxiety disorders and thyroid autoimmunity in a community sample. METHODS A community based sample of 222 subjects was examined. Psychiatric diagnoses were formulated using the International Composite Diagnostic Interview Simplified (CIDIS), according to DSM-IV criteria. All subjects underwent a complete thyroid evaluation including physical examination, thyroid echography and measure of serum free T4 (FT4), free T3 (FT3), thyroid-stimulating hormone (TSH) and anti-thyroid peroxidase autoantibodies (anti-TPO). RESULTS 16.6% of the overall sample had an anti-TPO value above the normal cut-off. Subjects with at least one diagnosis of anxiety disorders (OR = 4.2, C.L. 95% 1.9-38.8) or mood disorders (OR = 2.9, Cl 95% 1.4-6.6, P < 0.011) were positive for serum anti-TPO more frequently than subjects without mood or anxiety disorders. A statistically significant association with anti-TPO+ was found in Anxiety Disorder Not Otherwise Specified (OR = 4.0, CL 95% 1.1-15.5), in Major Depressive Episode (OR = 2.7, CL 95% 1.1-6.7) and Depressive Disorder Not Otherwise Specified (OR = 4.4, S CL 95% 1-19.3). CONCLUSIONS The study seems to suggest that individuals in the community with thyroid autoimmunity may be at high risk for mood and anxiety disorders. The psychiatric disorders and the autoimmune reaction seem to be rooted in a same (and not easy correctable) aberrancy in the immuno-endocrine system. Should our results be confirmed, the findings may be of great interest for future preventive and case finding projects.


title: Influenza surveillance in Victoria, 2004.

text: Influenza activity during the traditional Victorian influenza season from May to October 2004 was low with no well-defined peak. Surveillance was based on sentinel general practice influenza-like illness (ILI) notification with laboratory confirmation, locum service ILI notification and laboratory reporting of influenza detections. Eight hundred and fifteen consultations for ILI were reported from 38 general practices and 216 consultations for ILI were reported from the locum service. The average weekly rate of influenza-like-illness from sentinel surveillance was 5.4 cases per 1,000 consultations, representing normal seasonal activity. Influenza A (H3N2) was the predominant circulating sub-type, 88 per cent of which were identified as A/Fujian/411/2002-like and 12 per cent as A/Wellington/1/2004. All influenza B was B/Shanghai/361/2002-like. There was some mismatch with the 2004 influenza vaccine, which contained A/New Caledonia/20/99(H1N1)-like virus, A/Fujian/411/2002(H3N2)-like virus, and B/Hong Kong/330/2001-like virus.


title: Alternative methods of estimating an incubation distribution: examples from severe acute respiratory syndrome.

text: BACKGROUND Accurate and precise estimates of the incubation distribution of novel, emerging infectious diseases are vital to inform public health policy and to parameterize mathematical models. METHODS We discuss and compare different methods of estimating the incubation distribution allowing for interval censoring of exposures, using data from the severe acute respiratory syndrome (SARS) epidemic in 2003 as an example. RESULTS Combining data on unselected samples of 149 and 168 patients with defined exposure intervals from Toronto and Hong Kong, respectively, we estimated the mean and variance of the incubation period to be 5.1 day and 18.3 days and the 95th percentile to be 12.9 days. We conducted multiple linear regression on the log incubation times and found that incubation was significantly longer in Toronto than in Hong Kong and in older compared with younger patients, while it was significantly shorter in healthcare workers than in other patients. CONCLUSIONS Our findings suggest subtle but important heterogeneities in the incubation period of SARS among different strata of patients. Robust estimation of the incubation period should be independently carried out in different settings and subgroups for novel human pathogens using valid statistical methods.


title: Antiviral studies of feline infectious peritonitis virus in vitro.

text: Sixteen compounds were tested for their ability to inhibit the replication in vitro of feline infectious peritonitis virus (FIPV), a coronavirus that causes a lethal, immunologically mediated illness in domestic and exotic cats. Six of the compounds, when incubated with cells and titrations of the virus, were found to reduce the virus titres by 0.401 to 0.833 log10 (P < 0.05), using the cytopathic effect as endpoint. Further inhibition studies were performed to determine the 50 per cent effective dose (ED50) levels for these six compounds. Selectivity indices (50 per cent cytotoxic dose [CD50]/ED50) provided the following order of antiviral activity: pyrazofuin > 6-azauridine > 3-deazaguanosine > hygromycin B > fusidic acid > dipyridamole. Compounds which had no statistically significant effect on FIPV in the same assay were caffeic acid, carbodine, 3-deazauridine, 5-fluoroorotic acid, 5-fluorouracil, D(+)glucosamine, indomethacin, D-penicillamine, rhodamine and taurine.


title: Update on treatment of COVID-19: ongoing studies between promising and disappointing results.

text: The COVID-19 pandemic represents the greatest global public health crisis since the pandemic influenza outbreak of 1918. We are facing a new virus, so several antiviral agents previously used to treat other coronavirus infections such as SARS and MERS are being considered as the first potential candidates to treat COVID-19. Thus, several agents have been used by the beginning of the current outbreak in China first and all over the word successively, as reported in several different guidelines and therapeutic recommendations. At the same time, a great number of clinical trials have been launched to investigate the potential efficacy therapies for COVID-19 highlighting the urgent need to get as quickly as possible high-quality evidence. Through PubMed, we explored the relevant articles published on treatment of COVID-19 and on trials ongoing up to April 15, 2020.


title: Scanning electron, light, and immunofluorescent microscopy of intestine of gnotobiotic calf infected with calf diarrheal coronavirus.

text: Intestinal lesions in 2 gnotobiotic calves given (oral inoculation) calf diarrheal coronavirus were studied by scanning electron, light, and immunofluorescent microscopy. The calves were euthanatized at 34 and 73 hours after the onset of diarrhea. Lesions in the small intestine were similar to those reported in animals affected with transmissible gastroenteritis of swine. Small intestinal villi were shortened, some adjacent villi were fused, and villous epithelium was composed of low cuboidal to squamous cells. In the ansa spiralis coli, there were atrophy of the colonic ridges and marked differences in length and spacing of the microvilli on individual epithelial cells.


title: Integrating public health and primary care.

text: PURPOSE Improved health and social outcomes would be possible with better coordination and collaboration between public health and primary care. The purpose of this study is to identify linkages between these health sectors with the aim of informing a forward-looking policy approach to integrate public health functions in primary care. METHODS We searched national and international journals and the grey literature for relevant papers and reports published from January 1999 to December 2003. The final set of documents provided broad coverage of the topic, with emphasis on national and international representation and a special focus on disease surveillance, health promotion, accident and illness prevention and chronic diseases. RESULTS Three main findings emerged from this study. First, there is a need to understand and clearly articulate the roles and functions of public health and primary care in Canada. Second, the main areas of overlap between these sectors are health surveillance, health promotion and prevention of disease and injury. Third, based on an international literature search, we identified 10 models that demonstrate how these sectors can be integrated; five of them were developed in Canada. CONCLUSIONS National and international evidence and a variety of working models support the integration of public health functions in primary care. Canada has been a leader in developing models of integrated health systems that combine individualized approaches to influence personal health behaviour and community approaches to influence the health of the population. These integration models could be further developed through a focus on the common need of primary care and public health to address the health implications of the ever-present risk of emerging infectious diseases in Canada.


title: Host species barriers to influenza virus infections.

text: Most emerging infectious diseases in humans originate from animal reservoirs; to contain and eradicate these diseases we need to understand how and why some pathogens become capable of crossing host species barriers. Influenza virus illustrates the interaction of factors that limit the transmission and subsequent establishment of an infection in a novel host species. Influenza species barriers can be categorized into virus-host interactions occurring within individuals and host-host interactions, either within or between species, that affect transmission between individuals. Viral evolution can help surmount species barriers, principally by affecting virus-host interactions; however, evolving the capability for sustained transmission in a new host species represents a major adaptive challenge because the number of mutations required is often large.


title: Overview of antiviral and anti-inflammatory treatment for severe acute respiratory syndrome.

text: In 2003, an outbreak of a novel respiratory virus exploded from mainland China into an international issue, catching the world by surprise. The ensuing challenges to hospital and public health workers rose to a level never before seen in healthcare, in part due to the unknown nature of the disease, the fear of the human-to-human transmission and the significant media involvement. A new coronavirus was identified as the causative agent and named the severe acute respiratory syndrome-associated virus. A number of antiviral and anti-inflammatory treatment strategies were explored during the epidemic, with varying success. Following the epidemic, in vitro antiviral analyses of numerous compounds have been conducted. This review summarizes treatment agents assessed during and after the 2003 severe acute respiratory syndrome outbreak, with the aim of guiding future decision makers should the virus return.


For the library.


title: [Serological diagnostic studies of the occurrence of coronavirus infections in cattle with respiratory diseases].

text: Of paired serum samples of 196 cattle with respiratory disease from 37 herds which were tested for hemagglutination inhibiting antibodies against coronavirus (BCV) 185 of the first specimens and 190 of the second ones gave positive results. This difference was due to five animals of five different farms showing seroconversions between the time of the blood collections. A significant rise in antibody titer (no less than 4-fold) was evident in 28 cattle from 3 of the above mentioned and 12 other farms. Altogether serological indication of acute coronavirus infections were gained in 33 (16.8%) of animals with respiratory diseases which derived from 17 of 37 herds. Most of these infections (about 35%) occurred in animals older than 6 months while calves up to 3 or 6 months were only affected in a ratio of ca. 10%, respectively.


title: Design of Australasian intensive care units: time for change or time for more research?

text: Recommendations exist to guide the design and construction of adult intensive care units, but current guidelines are hampered by the paucity of high-quality research. Much of the current literature on ICU design has focused on patient-centred outcomes, such as nosocomial infections, aspects of psychological and physiological wellbeing, and patient satisfaction, but the design of the ICU environment also affects health care workers. The literature seems to favour the use of single rooms rather than an open-plan ICU design, with the major benefits being to infection control, but this notion is controversial. For most aspects of ICU design, more research is required before definite conclusions can be drawn. This article discusses the application of evidence-based design to improve the ICU environment and reviews some of the controversial issues and concepts.


title: Angiotensin-converting enzyme insertion/deletion polymorphism associated with acute respiratory distress syndrome among caucasians.

text: Studies investigating the association between angiotensin-converting enzyme (ACE) insertion/deletion polymorphisms and the risk of acute respiratory distress syndrome (ARDS) report conflicting results. The objective of the present study was to summarize quantitatively the evidence for such a relationship. Two investigators independently searched the MEDLINE (January 1966 - October 2009) and EMBASE (January 1980 - October 2009) databases. This meta-analysis included six case-control studies, which included 514 ARDS cases and 2619 controls. The combined results based on all studies showed that patients with ARDS had a significantly higher frequency of the ACE deletion/deletion (DD) genotype (odds ratio [OR] 1.56; 95% confidence interval [CI] 1.22, 2.00) than controls. When stratifying for race, no significant differences in genotype distribution were found except that Caucasian patients with ARDS had a significantly higher frequency of the DD genotype (OR 1.65; 95% CI 1.27, 2.13) than controls. This meta-analysis suggests that ACE insertion/deletion polymorphisms may be associated with ARDS among Caucasians.


title: The nucleocapsid protein of severe acute respiratory syndrome-coronavirus inhibits the activity of cyclin-cyclin-dependent kinase complex and blocks S phase progression in mammalian cells.

text: Deregulation of the cell cycle is a common strategy employed by many DNA and RNA viruses to trap and exploit the host cell machinery toward their own benefit. In many coronaviruses, the nucleocapsid protein (N protein) has been shown to inhibit cell cycle progression although the mechanism behind this is poorly understood. The N protein of severe acute respiratory syndrome-coronavirus (SARS-CoV) bears signature motifs for binding to cyclin and phosphorylation by cyclin-dependent kinase (CDK) and has recently been reported by us to get phosphorylated by the cyclin-CDK complex (Surjit, M., Kumar, R., Mishra, R. N., Reddy, M. K., Chow, V. T., and Lal, S. K. (2005) J. Virol. 79, 11476-11486). In the present study, we prove that the N protein of SARS-CoV can inhibit S phase progression in mammalian cell lines. N protein expression was found to directly inhibit the activity of the cyclin-CDK complex, resulting in hypophosphorylation of retinoblastoma protein with a concomitant down-regulation in E2F1-mediated transactivation. Coexpression of E2F1 under such conditions could restore the expression of S phase genes. Analysis of RXL and CDK phosphorylation mutant N protein identified the mechanism of inhibition of CDK4 and CDK2 activity to be different. Whereas N protein could directly bind to cyclin D and inhibit the activity of CDK4-cyclin D complex; inhibition of CDK2 activity appeared to be achieved in two different ways: indirectly by down-regulation of protein levels of CDK2, cyclin E, and cyclin A and by direct binding of N protein to CDK2-cyclin complex. Down-regulation of E2F1 targets was also observed in SARS-CoV-infected VeroE6 cells. These data suggest that the S phase inhibitory activity of the N protein may have major significance during viral pathogenesis.


title: Evaluating Protection Against Infectious Bronchitis Virus by Clinical Signs, Ciliostasis, Challenge Virus Detection, and Histopathology.

text: In this study, we examined the association among clinical signs, ciliostasis, virus detection, and histopathology for evaluating protection of vaccinated chickens against homologous and heterologous infectious bronchitis virus (IBV) challenge. At 5 days following challenge with IBV, we found a good correlation among clinical signs, ciliostasis in the trachea, challenge virus detection, and microscopic lesions in the trachea, with all four criteria being negative in fully protected birds and positive in fully susceptible birds. In partially protected birds we observed clinical signs and detected challenge virus; however, the ciliated epithelium was intact. In a second experiment, we challenged fully protected, partially protected, and fully susceptible birds with IBV, and then at 5 days postchallenge we gave the birds an opportunistic bacterium intranasally. Twenty Bordetella avium colonies were recovered from one of five fully protected birds, and only five colonies were isolated from two of five partially protected birds without ciliostasis, whereas in birds with ciliostasis, numerous colonies were isolated. Obviously, decreasing IBV infection and replication in the upper respiratory tract will decrease transmission and mutations, leading to variant viruses, and herein we demonstrate that protection of the cilia will decrease secondary bacterial infections, which have been shown to lead to condemnations and increased mortality. Thus, it appears that examining both criteria would be important when evaluating IBV vaccine efficacy.


title: Transmissible gastroenteritis coronavirus: the development and applications of the fixed-cell immunoperoxidase technique.

text: Since the first demonstration in 1971 that solid-phase enzyme-linked immunosorbent assays (ELISAs) could be used for the quantitative determination of antigens and antibodies, this method has been widely applied in serodiagnosis of parasitic and infectious diseases. In addition to the classic ELISA variants using antigen or antibody to coat the plastic plates, there has recently been growing interest in the application of fixed-cell ELISA to research and diagnostic work on viral diseases. The authors discuss the development and applications of this technique to basic research and diagnosis of transmissible gastroenteritis, a highly contagious disease of swine. The success of this technique, as the name suggests, is largely due to the use of a suitable fixative, which preserves the antigenicity of the neo-synthesised viral proteins, and the presence of optimal conditions for viral antigen synthesis. In addition, various parameters are optimised, and this is discussed with reference to transmissible gastroenteritis virus. These parameters would help veterinarians and research workers to develop this technique in their own laboratories.


title: High frequency RNA recombination in porcine reproductive and respiratory syndrome virus occurs preferentially between parental sequences with high similarity.

text: Two types of porcine reproductive and respiratory syndrome virus (PRRSV) exist, a North American type and a European type. The co-existence of both types in some countries, such as Denmark, Slovakia and Canada, creates a risk of inter-type recombination. To evaluate this risk, cell cultures were co-infected with either a North American and a European type of PRRSV or two diverse types of European isolate. Subsequently, an approximately 600 bp region of the PRRSV genome was tested for recombination by quantitative real-time RT-PCR. Between 0.1 and 2.5% RNA recombination was found between the European isolates, but no recombination was detected between the European and North American types. Calculation of the maximum theoretical risk of European-American recombination, based on the sensitivity of the RT-PCR system, revealed that RNA recombination between the European and North American types of PRRSV is at least 10 000 times less likely to occur than RNA recombination between diverse European isolates.


[One year later].


title: Part 1. Biologic responses in rats and mice to subchronic inhalation of diesel exhaust from U.S. 2007-compliant engines: report on 1-, 3-, and 12-month exposures in the ACES bioassay.

text: The Health Effects Institute and its partners conceived and funded a program to characterize the emissions from heavy-duty diesel engines compliant with the 2007 and 2010 on-road emissions standards in the United States and to evaluate indicators of lung toxicity in rats and mice exposed repeatedly to diesel exhaust (DE*) from 2007-compliant engines. The preliminary hypothesis of this Advanced Collaborative Emissions Study (ACES) was that 2007-compliant on-road diesel emissions ". . . will not cause an increase in tumor formation or substantial toxic effects in rats and mice at the highest concentration of exhaust that can be used . . . although some biological effects may occur." This hypothesis is being tested at the Lovelace Respiratory Research Institute (LRRI) by exposing rats by chronic inhalation as a carcinogenicity bioassay, measuring indicators of pulmonary toxicity in rats after 1, 3, 12, and 24-30 months of exposure (final time point depends on the survival of animals), and measuring similar indicators of pulmonary toxicity in mice after 1 and 3 months of exposure. This report provides results of exposures through 3 months in rats and mice. Emissions from a 2007-compliant, 500-horsepower-class engine and aftertreatment system operated on a variable-duty cycle were used to generate the animal inhalation test atmospheres. Four treatment groups were exposed to one of three concentrations (dilutions) of exhaust combined with crankcase emissions, or to clean air as a negative control. Dilutions of exhaust were set to yield average integrated concentrations of 4.2, 0.8, and 0.1 ppm nitrogen dioxide (NO2). Exposure atmospheres were analyzed by daily measurements of key components and periodic detailed physical-chemical characterizations. Exposures were conducted 16 hr/dy (overnight), 5 dy/wk. Rats were evaluated for hematology, serum chemistry, bronchoalveolar lavage (BAL), lung cell proliferation, and histopathology after 1 month of exposure, and the same indicators plus pulmonary function after 3 months. Mice were evaluated for BAL, lung cell proliferation, and respiratory tract histopathology after 1 month of exposure, and the same indicators plus hematology and serum chemistry after 3 months. Samples from both species were collected for ancillary studies performed by investigators who were not at LRRI and were funded separately. Exposures were accomplished as planned, with average integrated exposure concentrations within 20% of the target dilutions. The major components were the gaseous inorganic compounds, nitrogen monoxide (NO), NO2, and carbon monoxide (CO). Minor components included low concentrations of diesel particulate matter (DPM) and volatile and semivolatile organic compounds (VOCs and SVOCs). There were no exposure-related differences in mortality or clinically evident morbidity. Among the more than 100 biologic response variables evaluated, the majority showed no significant difference from control as a result of exposure to DE. There was evidence of early lung changes in the rats, accompanied by a number of statistically significant increases in inflammatory and oxidative stress indicators, and some evidence of subtle changes in pulmonary function. In general, statistically significant effects were observed only at the highest exposure level. The mice did not have the same responses as the rats, but did have small but statistically significant increases in lavage neutrophils and the cytokine IL-6 at 1 month (but not at 3 months). These findings suggest that the rats were more sensitive than mice to the subchronic exposures.


title: Regulatory oversight of human pathogens and toxins in Canada.

text: From 1994 to 2009, federal oversight of human pathogens and toxins was limited to facilities importing human pathogens and toxins into Canada under the Human Pathogens Importation Regulations (HPIR). This narrow focus of authority restricted the Government of Canada's ability to regulate and monitor a full range of activities, including those involving human pathogens and toxins acquired from domestic sources. In 2009, the Human Pathogens and Toxins Act (the Act) received Royal Assent to establish a national safety and security regime and expand oversight through a national, standardized process to verify safe and secure use of human pathogens and toxins in Canada. The Act and the Human Pathogens and Toxins Regulations (the Regulations), in full force since December 1, 2015, provides legislative and statutory requirements for the comprehensive oversight of the control of human pathogens and toxins in Canada. Expanded regulation and monitoring program activities aim to reduce the risks posed by human pathogens and toxins and strengthen biosafety management systems that serve to protect the health of Canadians.


title: Young children's perceptions of physicians wearing standard precautions versus customary attire.

text: OBJECTIVE The aim of the study was to determine if young children have a preference regarding whether physicians wear standard precautions attire. METHODS One hundred ninety-seven children, aged 4 to 8 years, and their parents were recruited from the pediatric emergency department of a tertiary care center. Two sets of 4 photographs-the same man in formal attire, a white coat, greens, and severe acute respiratory syndrome (SARS) standard precautions attire, and the same woman in formal attire, a white coat, greens, and SARS standard precautions attire-were shown to the children and their caregiver. Both were asked which physician's attire he or she liked the most and which he or she liked the least. Parents filled out a questionnaire regarding their experiences in the pediatric emergency department during the SARS epidemic. RESULTS The children selected the physician in SARS standard precautions attire as most liked 17.5% of the time and least liked 53.3% of the time. The parents selected the physician in SARS standard precautions attire as most liked 0% of the time and least liked 94.8% of the time. CONCLUSIONS Physicians wearing standard precautions attire while working in the pediatric emergency department need to be aware that this attire may negatively impact their relationship with pediatric patients 4 to 8 years of age.


title: Efficiency of quarantine during an epidemic of severe acute respiratory syndrome--Beijing, China, 2003.

text: During March--July 2003, an epidemic of severe acute respiratory syndrome (SARS) in Beijing, China, accounted for 2,521 probable cases (attack rate: 19 per 100,000 population). To control the epidemic, public health officials initiated enhanced surveillance, isolation of SARS patients, use of personal protective equipment (PPE) by health-care workers, and quarantine of contacts of known SARS patients. Approximately 30,000 Beijing residents were quarantined in their homes or quarantine sites. To guide future quarantine policy, the Chinese Field Epidemiology Training Program (China FETP) of the Chinese Center for Disease Control and Prevention (China CDC) conducted a survey to estimate the risk for acquiring SARS among quarantined residents of Haidian District (2001 population: 2.24 million), Beijing, in May 2003, 1 month after the epidemic peaked. This report summarizes the results of that survey, which indicate that, as a component of a comprehensive SARS-control program, quarantine should be limited to persons who have contact with an actively ill SARS patient in the home or hospital, allowing for better focus of resources in future outbreaks.


Incidental Gastric Fundus Diverticulum during Laparoscopic Sleeve Gastrectomy.


title: [Lung pathology of severe acute respiratory syndrome].

text: OBJECTIVE To study the morphological features of the lungs obtained from autopsies of severe acute respiratory syndrome (SARS) patients. METHODS Bilateral lungs from 7 patients died from SARS were carefully studied grossly and microscopically. All tissues from these cases were routinely processed and carefully studied. RESULTS All lungs from these cases were extremely expanded and became solid. Microscopically, the edema and fibrin exudates in the alveoli was the most common findings, especially in the early phase of the disease. The hyaline membrane was almost always present in the lungs of these cases. The organization of intra-alveolar fibrin exudates along with the interstitial fibrosis led to obliteration of alveoli and consolidation of lungs. The desquamation and hyperplasia of alveolar lining cells was also apparent. Foci of haemorrhage and lobular pneumonia, even diffuse fungal infection were frequently seen in these specimens. Micro-thrombus were easily found in these lungs. CONCLUSIONS The lung of SARS from autopsy is characterized by edema, intra-alveolar fibrin exudates, hyaline membrane formation, organization of intra-alveolar exudates and fibrosis, which lead to the obliteration of alveoli and consolidation of lungs.


title: Occupational health and infection control practices related to severe acute respiratory syndrome: health care worker perceptions.

text: The spread of severe acute respiratory syndrome (SARS) in 2003 was largely driven by hospital-associated transmission where health care workers experienced the largest burden of disease. In attempting to improve occupational health and infection control procedures to prevent occupationally acquired infections in health care workers, it is important to examine the perceptions of those workers who are expected to adhere to specific policies. The authors conducted 15 focus groups of health care workers representing seven different job classifications in two Canadian provinces where SARS outbreaks occurred in 2003 using a theoretical framework which divided factors associated with self-protective behaviour at work into organizational, environmental, and individual factors. Content analysis of these discussions revealed that workers placed more importance on organizational factors than environmental and individual factors. The results are similar to those of a recently completed literature review of this subject, and should be considered when developing new occupational health initiatives to protect health care workers from existing or emerging respiratory tract infections.


title: Nasal cytology in patients with allergic rhinitis: effects of intranasal fluticasone propionate.

text: BACKGROUND Nasal cytograms of patients with allergic rhinitis contain increased numbers of eosinophils and basophilic cells. Neutrophils are also more numerous in cytograms of allergic persons. Topical intranasal corticosteroid therapy for allergic rhinitis has been shown to decrease the numbers of some inflammatory cell types. Fluticasone propionate aqueous nasal spray, a potent synthetic corticosteroid preparation, is effective therapy for seasonal and perennial allergic rhinitis. METHODS Nasal mucosal scrapings were obtained with a Rhinoprobe (Apotex Scientific, Inc. Arlington, Texas) before and after therapy with fluticasone propionate aqueous nasal spray at several doses in patients with either seasonal allergic rhinitis (2 to 4 weeks' therapy) or perennial allergic rhinitis (24 weeks' therapy). More than 1000 paired nasal cytograms obtained from patients participating in five multicenter studies were evaluated. RESULTS The percentage of patients with nasal eosinophils (p < 0.01, most studies) and basophilic cells (p < 0.05, most studies) decreased significantly after treatment with fluticasone propionate compared with placebo-treated patients. Similar findings were observed with beclomethasone dipropionate in one study. The number of neutrophils remained relatively unchanged after treatment with the intranasal corticosteroids or placebo. CONCLUSIONS These findings suggest that the therapeutic benefits of topical intranasal fluticasone propionate and beclomethasone dipropionate for the therapy of seasonal and perennial allergic rhinitis are reflected by the decrease in inflammatory cells in the nasal mucosa.


Diabetes and COVID-19-the meeting of two pandemics: what are the concerns?


Genetic recombination in RNA viruses.


title: Role of respiratory viruses in acute upper and lower respiratory tract illness in the first year of life: a birth cohort study.

text: INTRODUCTION Although acute respiratory illnesses (ARI) are major causes of morbidity and mortality in early childhood worldwide, little progress has been made in their control and prophylaxis. Most studies have focused on hospitalized children or children from closed populations. It is essential that the viral etiology of these clinical diseases be accurately defined in the development of antiviral drugs. OBJECTIVE To investigate the role of all common respiratory viruses as upper and lower respiratory tract pathogens in the first year of life. STUDY DESIGN This community-based birth cohort study prospectively collected detailed information on all ARI contracted by 263 infants from birth until 1 year of age. Nasopharyngeal aspirates were collected for each ARI episode, and all common respiratory viruses were detected by polymerase chain reaction. Episodes were classified as upper respiratory illnesses or lower respiratory illnesses (LRI), with or without wheeze. RESULTS The majority reported 2-5 episodes of ARI in the first year (range, 0-11 episodes; mean, 4.1). One-third were LRI, and 29% of these were associated with wheeze. Viruses were detected in 69% of ARI; most common were rhinoviruses (48.5%) and respiratory syncytial virus (RSV) (10.9%). Compared with RSV, >10 times the number of upper respiratory illnesses and >3 times the number of both LRI and wheezing LRI were attributed to rhinoviruses. CONCLUSION Rhinoviruses are the major upper and lower respiratory pathogens in the first year of life. Although RSV is strongly associated with severe LRI requiring hospitalization, the role of rhinoviruses as the major lower respiratory pathogens in infants has not previously been recognized.


title: The spleen as a target in severe acute respiratory syndrome.

text: It has been proposed that immune injury is the central mechanism of pathogenesis of the infectious disease, severe acute respiratory syndrome (SARS). To gain a better understanding of immune injury in the spleen, we investigated the number and distribution of various immune cell types in the spleens of SARS patients. We performed autopsies on six confirmed SARS cases, with six normal subjects as controls; spleen samples from these autopsies were examined with hematoxylin and eosin (H&E) sections, in situ hybridization for SARS virus genomic sequences, and immunohistochemistry with seven monoclonal antibodies to five cell types. The number and distribution of these cells were measured and analyzed using an image analysis system. SARS genomic sequences were detected in all SARS spleens. The SARS spleens all had severe damage to the white pulp and showed an alteration of the normal distribution of various cell types. Immunocytes in the red pulp were decreased by 68.0-90.7% except for CD68+ macrophages and human leukocyte antigen (HLA)-DR positive antigen-presenting cells (APC), which were decreased to a lesser degree. On average, CD68+ macrophages were increased in size by 2.21-fold. We hypothesize that the collapse of the splenic immune system plays a key role in the clinical outcome of these patients.


title: Potent cross-reactive neutralization of SARS coronavirus isolates by human monoclonal antibodies.

text: The severe acute respiratory syndrome coronavirus (SARS-CoV) caused a worldwide epidemic in late 2002/early 2003 and a second outbreak in the winter of 2003/2004 by an independent animal-to-human transmission. The GD03 strain, which was isolated from an index patient of the second outbreak, was reported to resist neutralization by the human monoclonal antibodies (hmAbs) 80R and S3.1, which can potently neutralize isolates from the first outbreak. Here we report that two hmAbs, m396 and S230.15, potently neutralized GD03 and representative isolates from the first SARS outbreak (Urbani, Tor2) and from palm civets (SZ3, SZ16). These antibodies also protected mice challenged with the Urbani or recombinant viruses bearing the GD03 and SZ16 spike (S) glycoproteins. Both antibodies competed with the SARS-CoV receptor, ACE2, for binding to the receptor-binding domain (RBD), suggesting a mechanism of neutralization that involves interference with the SARS-CoV-ACE2 interaction. Two putative hot-spot residues in the RBD (Ile-489 and Tyr-491) were identified within the SARS-CoV spike that likely contribute to most of the m396-binding energy. Residues Ile-489 and Tyr-491 are highly conserved within the SARS-CoV spike, indicating a possible mechanism of the m396 cross-reactivity. Sequence analysis and mutagenesis data show that m396 might neutralize all zoonotic and epidemic SARS-CoV isolates with known sequences, except strains derived from bats. These antibodies exhibit cross-reactivity against isolates from the two SARS outbreaks and palm civets and could have potential applications for diagnosis, prophylaxis, and treatment of SARS-CoV infections.


Travel-acquired infections in general.


Oropharyngeal carriage of Neisseria gonorrhoeae and its response to treatment in patients with anogenital infection.


On terrorism--2.


title: The making of a Chinese head of the WHO: a study of the media discourse on Margaret Chan's contest for the WHO director-generalship and its implications for the collective memory of SARS.

text: In 2003, Margaret Chan Fung Fu-chun, former Director of Health of the Hong Kong government, was criticized for her unsatisfactory performance in handling the SARS outbreak. But three years later, she was celebrated for her success in the contest for the WHO director-generalship. How was she transformed from an incompetent official into an "honor winner" for China and Hong Kong? In what context was this made possible? How was the collective memory about Chan recalled and reconstructed? This article tackles these questions by reviewing relevant reportage and commentary in major local (Hong Kong), national (China), and international media. It maps the political context of the media discourse and explores the construction of a collective past to foster national cohesion in postcolonial Hong Kong.


title: Viet Nam.

text: Attention in this discussion of Viet Nam focuses on the following: history of the demographic situation; the government's overall approach to population problems; population data systems and development planning; institutional arangements for the integration of population within development planning; the government's view of the importance of population policy in achieving development objectives; population size, growth, and natural increase; morbidity and mortality; fertility; international migration; and spatial distribution. Relatively little information has been available on demographic trends in Viet Nam due to the absence of any major survey or census until the last few decades. The government increasingly has been concerned about the high rate of population growth and is working to change the situation through programs directed at fertility reduction. As part of its program for overall social and economic restructuring, the government seeks to give special attention to health problems, particularly those relating to maternal and child health and environmental sanitation. Population censuses in Viet Nam have been undertaken only in the last 2 decades, with censuses conducted in the North in 1960 and 1974. No population census was undertaken in the South, and any population information available was based upon the periodic population and household surveys conducted alternately in different provinces, cities, and rural areas during 1962, 1967, 1971, and 1974. The government considers the formulation and implementation of population policy to be a critical variable for realizing national development objectives. The population of Viet Nam has grown considerably since the 1950s, increasing from over 30 million in 1950 to 35.4 million in 1960 and reaching 43.1 million by 1970, according to UN estimates. 1979 census results indicate that the population of Viet Nam had reached 52.7 million. The current rate of growth is estimated at 2.2%. The government perceives the current rate of population growth as unsatisfactory because it is too high. The official government policy is to take steps to reduce the rate of population growth as rapidly as possible. All 3 demographic factors--mortality, fertility, and spatial distribution--are viewed as subject to direct policy intervention to achieve this goal. Rates of morbidity and mortality have declined considerably in the past few decades. The government reports a decline in the crude death rate from 12.2 in 1957 to 7.0 in 1980 and an increase in the life expectancy at birth from 34 years in 1936 to 60 in 1978. UN estimates are considerably higher. According to UN estimates, the infant mortality rate was 90.3/1000 live births during 1975-80 for Viet Nam as a whole. The current mortality and morbidity situation is considered to be unacceptable. The government estimates the crude birthrate as 29.3/1000 in 1980, an unsatisfactory level. The government perceives the present levels and trends of immigration as not significant and satisfactory and the spatial distribution as inappropriate.


title: High-resolution CT findings in patients with severe acute respiratory syndrome: a pattern-based approach.

text: OBJECTIVE We retrospectively reviewed high-resolution CT (HRCT) examinations of the lungs performed in 27 confirmed cases of severe acute respiratory syndrome (SARS). The HRCT findings at different phases of the illness were analyzed. CONCLUSION A defined pattern of HRCT findings is observed in different phases of SARS, which is characterized by focal ground-glass and crazy paving patterns in a scattered distribution at presentation, followed by development of interstitial thickening, consolidation, pleural reaction, and scarring. Spontaneous pneumomediastinum is a distinct complication during the course of the illness.


title: Pulmonary sequelae of severe H1N1 infection treated with high frequency oscillatory ventilation.

text: During the recent influenza A (H1N1) pandemic, due to severe respiratory failure many patients required treatment with alternative ventilator modalities including High Frequency Oscillatory Ventilation (HFOV). We present four such patients treated with HFOV at an academic, tertiary referral hospital in Ireland. We detail outcomes of clinical examination, pulmonary function testing, quality of life assessment and radiographic appearance on CT Thorax at follow-up at 6 months. Further clinical assessment and pulmonary function testing were performed at median 19 months (range 18-21 months) post-discharge. At initial review all patients were found to have reduced gas transfer (median predicted DLCO 74%) with preservation of lung volumes and normal spirometrical values at 6 months (median FVC 5.42L [101% predicted] and FEV14.5L [101.2% predicted] respectively), with improvements in gas transfer (median predicted DLCO 83%)at subsequent testing. Post-inflammatory changes on CT thorax at 6 months were seen in all 4 cases. To our knowledge this is the first report to document the long-term effects of severe H1N1 infection requiring high frequency oscillation on respiratory function. We conclude that the effects on respiratory function and pulmonary radiological appearance are similar to those observed following conventional treatment of Acute Respiratory Distress Syndrome [ARDS].


title: Dynamically modeling SARS and other newly emerging respiratory illnesses: past, present, and future.

text: The emergence and rapid global spread of the severe acute respiratory syndrome (SARS) coronavirus in 2002-2003 prompted efforts by modelers to characterize SARS epidemiology and inform control policies. We overview and discuss models for emerging infectious diseases (EIDs), provide a critical survey of SARS modeling literature, and discuss promising future directions for research. We reconcile discrepancies between published estimates of the basic reproductive number R0 for SARS (a crucial epidemiologic parameter), discuss insights regarding SARS control measures that have emerged uniquely from a modeling approach, and argue that high priorities for future modeling of SARS and similar respiratory EIDs should include informing quarantine policy and better understanding the impact of population heterogeneity on transmission patterns.


title: Control of coronavirus infection through plasmacytoid dendritic-cell-derived type I interferon.

text: This study demonstrates a unique and crucial role of plasmacytoid dendritic cells (pDCs) and pDC-derived type I interferons (IFNs) in the pathogenesis of mouse coronavirus infection. pDCs controlled the fast replicating mouse hepatitis virus (MHV) through the immediate production of type I IFNs. Recognition of MHV by pDCs was mediated via TLR7 ensuring a swift IFN-alpha production following encounter with this cytopathic RNA virus. Furthermore, the particular type I IFN response pattern was not restricted to the murine coronavirus, but was also found in infection with the highly cytopathic human severe acute respiratory syndrome (SARS) coronavirus. Taken together, our results suggest that rapid production of type I IFNs by pDCs is essential for the control of potentially lethal coronavirus infections.


title: PKR-dependent autophagic degradation of herpes simplex virus type 1.

text: The lysosomal pathway of autophagy is the major catabolic mechanism for degrading long-lived cellular proteins and cytoplasmic organelles. Recent studies have also shown that autophagy (xenophagy) may be used to degrade bacterial pathogens that invade intracellularly. However, it is not yet known whether xenophagy is a mechanism for degrading viruses. Previously, we showed that autophagy induction requires the antiviral eIF2alpha kinase signaling pathway (including PKR and eIF2alpha) and that this function of eIF2alpha kinase signaling is antagonized by the herpes simplex virus (HSV-1) neurovirulence gene product, ICP34.5. Here, we show quantitative morphologic evidence of PKR-dependent xenophagic degradation of herpes simplex virions and biochemical evidence of PKR and eIF2alpha-dependent degradation of HSV-1 proteins, both of which are blocked by ICP34.5. Together, these findings indicate that xenophagy degrades HSV-1 and that this cellular function is antagonized by the HSV-1 neurovirulence gene product, ICP34.5. Thus, autophagy-related pathways are involved in degrading not only cellular constituents and intracellular bacteria, but also viruses.


title: 7a protein of severe acute respiratory syndrome coronavirus inhibits cellular protein synthesis and activates p38 mitogen-activated protein kinase.

text: It was recently shown that the 7a protein of severe acute respiratory syndrome coronavirus induces biochemical changes associated with apoptosis. In this study, the mechanism by which the 7a protein induces apoptosis was examined. The 7a protein was tested for the ability to inhibit cellular gene expression because several proapoptotic viral proteins with this function have previously been identified. 7a protein inhibited expression of luciferase from an mRNA construct that specifically measures translation, whereas inhibitors of transcription and nucleocytoplasmic transport did not. The inhibition of translation and other cellular processes of gene expression have been associated with the induction of a stress response in cells. Western blot analysis using phosphospecific antibodies indicated that 7a protein activated p38 mitogen-activated protein kinase (MAPK), but not c-Jun N-terminal protein kinase/stress-activated protein kinase. Taken together, these data indicate that the induction of apoptosis by the 7a protein may be related to its ability to inhibit cellular translation and activate p38 MAPK.


title: The location of asparagine-linked glycans on West Nile virions controls their interactions with CD209 (dendritic cell-specific ICAM-3 grabbing nonintegrin).

text: Mammalian cell-derived West Nile virus preferentially infects cells expressing the C-type lectin CD209L (dendritic cellspecific ICAM-3 grabbing nonintegrin-related protein; liver- and lymph node-specific ICAM-3 grabbing nonintegrin) but not cells expressing CD209 (dendritic cell-specific ICAM-3 grabbing nonintegrin). In contrast, Dengue virus infection is enhanced in cells expressing either attachment factor. The West Nile virus envelope (E) protein contains a single N-linked glycosylation site at residue 154, whereas Dengue virus E contains sites at residues 153 and 67. We introduced a glycosylation site at position 67 into West Nile virus E. Reporter virus particles pseudotyped with this E protein infected cells using either CD209 or CD209L. We also introduced glycosylation sites at several novel positions. All sites allowed CD209L-mediated infection, but only a subset promoted CD209 use. As seen for other viruses, mannose-rich glycans on West Nile virus were required for its interactions with CD209. Surprisingly, however, mannose-rich glycans were not required for CD209L-mediated infection. Complex glycans, particularly N-acetylglucosamine-terminated structures, were able to mediate reporter virus particle interactions with CD209L. We propose that CD209L recognizes glycosylated flaviviruses with broad specificity, whereas CD209 is selective for flaviviruses bearing mannose-rich glycans. The location of the N-linked glycosylation sites on a virion determines the types of glycans incorporated, thus controlling viral tropism for CD209-expressing cells.


title: HIV legal precedent useful for microbial forensics.

text: The field of microbial forensics was formalized because of the need for attribution in events where a bioweapon has been used. Microbial forensics has its origins in traditional forensics, microbiology, and epidemiology. Microbial forensics can be defined as a scientific discipline dedicated to analyzing evidence for attribution purposes from a bioterrorism act, biocrime, hoax, or inadvertent microorganism/toxin release. This is a very challenging task, since there are myriad microorganisms that can pose a threat, and analytical methods need to be used reliably. The Scientific Working Group on Microbial Genetics and Forensics (SWGMGF) has addressed some quality assurance and control issues, and particularly validation criteria (focusing on preliminary validation) due to the dynamic nature of evolving investigations. Unique identification of a microorganism may never be possible. Yet, qualitative and/or quantitative assessments of the evidence can be made. One approach to provide direction on gaps in the microbial forensics effort is to perform an end-to-end retrospective analysis of past cases. As an example, the case of a gastroenterologist who was accused of second degree attempted murder of his paramour using HIV as the weapon was reviewed. The scientific evaluation involves epidemiology, molecular biology, phylogenetics, and legal deliberations.


Immunogenetics in SARS: a case-control study.


title: Molecular biological analysis of genotyping and phylogeny of severe acute respiratory syndrome associated coronavirus.

text: BACKGROUND SARS-CoV is the causative agent of severe acute respiratory syndrome (SARS) which has been associated with outbreaks of SARS in Guangdong, Hong Kong and Beijing of China, and other regions worldwide. SARS-CoV from human has shown some variations but its origin is still unknown. The genotyping and phylogeny of SARS-CoV were analyzed and reported in this paper. METHODS Full or partial genomes of 44 SARS-CoV strains were collected from GenBank. The genotype, single nucleotide polymorphism and phylogeny of these SARS-CoV strains were analyzed by molecular biological, bioinformatic and epidemiological methods. RESULTS There were 188 point mutations in the 33 virus full genomes with the counts of mutation mounting to 297. Further analysis was carried out among 36 of 188 loci with more than two times of mutation. All the 36 mutation loci occurred in coding sequences and 22 loci were non-synonymous. The gene mutation rates of replicase 1AB, S2 domain of spike glycoprotein and nucleocapsid protein were lower (0.079% - 0.103%). There were 4 mutation loci in S1 domain of spike glycoprotein. The gene mutation rate of ORF10 was the highest (3.333%) with 4 mutation loci in this small domain (120 bp) and 3 of 4 loci related to deletion mutation. By bioinformatics processing and analysis, the nucleotides at 7 loci of genome (T:T:A:G:T:C:T/C:G:G:A:C:T:C) can classify SARS-CoV into two types. Therefore a novel definition is put forward that according to these 7 loci of mutation, 40 strains of SARS-CoV in GenBank can be grouped into two genotypes, T:T:A:G:T:C:T and C:G:G:A:C:T:C, and named as SARS-CoV Yexin genotype and Xiaohong genotype. The two genotypes can be further divided into some sub-genotypes. These genotypes can also be approved by phylogenetic tree of three levels of 44 loci of mutation, spike glycoprotein gene and complete genome sequence. Compared to various strains among SARS-CoV Yexin genotype and Xiaohong genotype, GD01 strain of Yexin genotype is more closely related to SARS-CoV like-virus from animals. CONCLUSION The results mentioned above suggest that SARS-CoV is responding to host immunological pressures and experiencing variation which provide clues, information and evidence of molecular biology for the clinical pathology, vaccine developing and epidemic investigation.


Glove port single-incision laparoscopic splenectomy and the treatment of its complications.


title: [Serological analysis of SARS Coronavirus in children diagnosed clinically as severe acute respiratory syndrome cases during SARS epidemic in Beijing].

text: OBJECTIVE To identify the etiologic agents from children who had been clinically diagnosed as severe acute respiratory syndrome (SARS) during the epidemic in Beijing and to characterize the transmissibility of SARS from those children to others. METHODS One hundred and seventy-seven serum specimens were collected during the period of June to August, 2003 from children and adults who had been clinically diagnosed as SARS and who closely contacted with those diagnosed as SARS during SARS epidemic in Beijing. Serum specimens were also collected from 49 children from Anhui province which was non-epidemic region and 93 healthy kindergarten children without history of contacting with SARS patients in Beijing during SARS epidemic. Serum specimens collected from 90 healthy kindergarten children in Beijing in September 2002 were included in the study. All the 409 serum specimens were tested for specific antibodies against SARS-associated coronavirus (SARS-CoV) by different methods including ELISA for specific IgM and IgG, whole antibodies against SARS-CoV, IFA for specific IgM and IgG against SARS-CoV, and Western-blot for IgG to expressed N protein from SARS-CoV. RESULTS The positive rates of specific IgG and whole antibodies against SARS-CoV ranged from 39.1% to 43.5% in the children who had been clinically diagnosed as SARS, zero in children and 6.0% to 9.0% in adults who had closely contacted with the clinically diagnosed SARS children. Among those clinically diagnosed SARS adult patients, the positive rates of specific IgG and whole antibodies against SARS-CoV were 57.1% to 71.4%. In children and adults who closely contacted with these clinically diagnosed SARS adult patients, the positive rates of specific IgG and whole antibodies against SARS-CoV were 0 to 9.7% and 4.4% to 7.1%, respectively. None of the serum specimens collected from healthy children before and during epidemic in Beijing and children from non-epidemic region was positive when IFA methods and ELISA with Beier kits were used for detection, but some were positive when ELISA with the diagnostic kit from other source was applied. CONCLUSION The positive rates of specific IgG and whole antibodies against SARS-CoV in children who had been clinically diagnosed as SARS were around 40%, which is much lower than the positive rate in clinically diagnosed adult SARS patients, indicating that a large proportion of those "SARS" children were infected with respiratory viruses other than SARS-CoV during SARS epidemic in Beijing. Some of the children who closely contacted with children and adults SARS patients showed positive SARS-CoV antibodies, suggesting that asymptomatic infections may occur. The value of some approved diagnostic kit at least in children for SARS etiological diagnosis needs to be analyzed further.


Automatic gas-powered resuscitators: what is their role in mass critical care?


Induction of apoptosis in murine coronavirus-infected 17Cl-1 cells.


Immunity for immunizations: tort liability, biodefense, and Bioshield II.


title: A single mutation in the E2 glycoprotein important for neurovirulence influences binding of sindbis virus to neuroblastoma cells.

text: The amino acid at position 55 of the E2 glycoprotein (E2(55)) of Sindbis virus (SV) is a critical determinant of SV neurovirulence in mice. Recombinant virus strain TE (E2(55) = histidine) differs only at this position from virus strain 633 (E2(55)= glutamine), yet TE is considerably more neurovirulent than 633. TE replicates better than 633 in a neuroblastoma cell line (N18), but similarly in BHK cells. Immunofluorescence staining showed that most N18 cells were infected by TE at a multiplicity of infection (MOI) of 50 to 500 and by 633 only at an MOI of 5,000, while both viruses infected essentially 100% of BHK cells at an MOI of 5. When exposed to pH 5, TE and 633 viruses fused to similar extents with liposomes derived from BHK or N18 cell lipids, but fusion with N18-derived liposomes was less extensive (15 to 20%) than fusion with BHK-derived liposomes ( approximately 50%). Binding of TE and 633 to N18, but not BHK, cells was dependent on the medium used for virus binding. Differences between TE and 633 binding to N18 cells were evident in Dulbecco's modified Eagle medium (DMEM), but not in RPMI. In DMEM, the binding efficiency of 633 decreased significantly as the pH was raised from 6.5 to 8.0, while that of TE did not change. The same pattern was observed with RPMI when the ionic strength of RPMI was increased to that of DMEM. TE bound better to heparin-Sepharose than 633, but this difference was not pH dependent. Growth of N18 and BHK cells in sodium chlorate to eliminate all sulfation decreased virus-cell binding, suggesting the involvement of sulfated molecules on the cell surface. Taken together, the presence of glutamine at E2(55) impairs SV binding to neural cells under conditions characteristic of interstitial fluid. We conclude that mutation to histidine participates in or stabilizes the interaction between the virus and the surface of neural cells, contributing to greater neurovirulence.


Fatal aspergillosis in a patient with SARS who was treated with corticosteroids.


title: [Chiroptera and zoonosis: an emerging problem on all five continents].

text: Zoonosis is the cause of the vast majority of emerging diseases. Bats that occupy the second place in the mammal class play an important role. Whether they belong to the microchiroptera suborder or to the megachiroptera suborder, bats on all five continents have been implicated in transmission of numerous pathogens including not only viruses such as Lyssavirus (e.g. rabies), Hepanivirus (e.g. Hendra and Nipah virus) and recently coronavirus (e.g. SARS-like coronavirus and Ebola virus) but also fungus such as histoplasmosis. By modifying environmental conditions and encroaching on their biotope, human intervention has probably contributed to the introduction of chiropteras into an epidemiologic chain in which they previously had no place, thus promoting the emergence of new pathogens.


title: Human rotavirus enteritis induced in conventional piglets. Intestinal structure and transport.

text: To better understand the pathogenesis of infantile viral gastroenteritis, we studied Na+ and Cl- fluxes in vitro in short-circuited jejunal epithelium from 8-10-day-old piglets after infection with a standard dose of human rotavirus given via nasogastric tube. 11 infected piglets, all of whom became ill, were compared with 9 uninfected, healthy litter-mates. When killed 72 h after infection, intestinal villi were shorter and crypts deeper (P less than 0.025) in duodenum, upper jejunum, and mid-small intestine, but not ileum in infected piglets. Virus antigen was seen by fluorescence microscopy in occasional jejunal villus tip cells in only four infected piglets and no controls at 72 h. Net Na+ and Cl- fluxes did not differ from noninfected litter-mate controls under basal conditions, but response to glucose was blunted in infected piglets (P less than 0.001). Theophylline stimulated net Cl- secretion in both infected and control animals, and cyclic AMP concentration in isolated jejunal villus enterocytes did not differ significantly. In isolated jejunal villus enterocytes of infected piglets, thymidine kinase activity increased (P less than 0.001), and sucrase activity decreased (P less than 0.001). We conclude that in this invasive enteritis caused by a major human viral pathogen, glucose-coupled Na+ transport is impaired in the jejunum at a time when the villus epithelium shows enzyme characteristics of crypt epithelium, and when little or no virus is present. These findings are identical to those occurring in an invasive coronavirus enteritis of piglets but differ markedly from those seen with enterotoxigenic diarrhea.


Coroner criticised over conduct of SARS inquest.


title: [An update on viral diseases of the dog and cat].

text: In this review, recent developments in the field of viral diseases of the dog and the cat are discussed. In the dog, infection with the coronavirus type 2 is associated with respiratory signs, while infection of a highly pathogenic strain of the coronavirus type 1 has been identified as the cause of mortality in puppies. A new strain of the canine parvovirus is identified, from which the pathogenicity is not yet completely clarified. Infection with West Nile virus is associated with progressive neurological disease and subclinical infections in dogs. Infection with equine influenza A (H3N8) or a highly related influenza virus can cause severe respiratory disease and mortality in greyhounds and other dogs. Infection with avian influenza A (H5N1) can cause disease and mortality in cats and is mostly subclinical in dogs. A number of outbreaks of highly virulent strains of the calicivirus in cats have been described.


title: The metropolitan acid aerosol characterization study: results from the summer 1994 Washington, D.C. field study.

text: An ambient particle monitoring study was conducted in Washington, D.C. during the summer of 1994 as part of the Metropolitan Acid Aerosol Characterization Study (MAACS). Acid aerosol and inhalable (particulate matter with aerodynamic diameters < 10 micron; PM10) and fine (particulate matter with aerodynamic diameters < 2.5 micron; PM2.5) particle samples were collected for 24-hr periods (9 A.M.-9 A.M. EDT) on alternate days at six monitoring sites located throughout the greater Washington, D.C. area. Monitoring sites were located in both urban and rural areas and were generally situated along a southwest to northeast line due to the prevailing winds. Information on site characteristics, including population density and distance from the city center, was also obtained, as were data on meteorological parameters. Results from this study show strong correlations among the particulate measures, PM10, PM2.5, SO4(2-), and H+. These strong correlations resulted from the fact that PM2.5 comprised 77% of PM10, with SO4(2-)-related species accounting for 49% of total PM2.5. PM10, PM2.5, SO4(2-), and H+ concentrations were found to be uniform across the metropolitan Washington area. Spatial variation was found, however, for coarse particles (PM2.5-10) and NH3 concentrations. In our previous Philadelphia study, population density was an important determinant of spatial variation in coarse particles and NH3 concentrations, however, in Washington, D.C., population density was not associated with observed spatial patterns in coarse particle concentrations, but was an important determinant of NH3 concentrations. When data from one site (Reservoir) was excluded from the analysis, population density explained larger percentage of the variability in NH3 levels and became an important determinant of the H+/SO4(2-) ratio as well. Ambient H+ models developed from Philadelphia data were found to predict H+ concentrations in Washington, D.C. reasonably well, representing an improvement over measurements made at a single stationary ambient monitoring site.


title: Semiparametric Relative-risk Regression for Infectious Disease Transmission Data.

text: This paper introduces semiparametric relative-risk regression models for infectious disease data. The units of analysis in these models are pairs of individuals at risk of transmission. The hazard of infectious contact from i to j consists of a baseline hazard multiplied by a relative risk function that can be a function of infectiousness covariates for i, susceptibliity covariates for j, and pairwise covariates. When who-infects-whom is observed, we derive a profile likelihood maximized over all possible baseline hazard functions that is similar to the Cox partial likelihood. When who-infects-whom is not observed, we derive an EM algorithm to maximize the profile likelihood integrated over all possible combinations of who-infected-whom. This extends the most important class of regression models in survival analysis to infectious disease epidemiology. These methods can be implemented in standard statistical software, and they will be able to address important scientific questions about emerging infectious diseases with greater clarity, flexibility, and rigor than current statistical methods allow.


title: Exploring passive transfer in muskoxen (Ovibos moschatus).

text: Poor calf production and ill thrift in 3-4 mo olds are common limiting problems in raising and maintaining captive muskoxen (Ovibos moschatus). Acute onset of a rapidly progressing enteritis and septicemia in neonatal calves (2-7 days of age) caused by Escherichia coli not normally considered pathogenic in domestic animals is a serious problem in many captive muskoxen facilities. Serum immunoglobulin G (IgG) levels, total protein, albumin, and globulin levels in captive periparturient muskox females and their neonatal calves were compared with levels found in other species in which these parameters have been well described. Results showed that all females in the study had IgG present in their serum (mean = 1,232.14 mg/dl, SD = 178.34 mg/dl, as measured via radial immunodiffusion). Calves were probably born agammaglobulinemic or hypogammaglobulinemic. IgG levels quickly rose in calves after initial colostrum intake to levels similar to those seen in other domestic ruminants. Our results suggest that passive transfer of immunity in muskoxen is similar to what is reported in domestic livestock and that reference ranges from domestic cattle may be used to assist interpretation of serum IgG levels in muskoxen. In addition, the positive relationship between serum protein and globulin levels with serum IgG levels is similar to that reported for Holstein cattle and thus provides a useful indicator of passive transfer in muskoxen.


Development of interfering RNA agents to inhibit SARS-associated coronavirus infection and replication.


title: Veterinary public health capacity in the United States: opportunities for improvement.

text: OBJECTIVES In 2006, the Association of American Veterinary Medical Colleges reported that the shortage (≥ 1,500) of public health veterinarians is expected to increase tenfold by 2020. In 2008, the Centers for Disease Control and Prevention (CDC) Preventive Medicine Fellows conducted a pilot project among CDC veterinarians to identify national veterinary public health workforce concerns and potential policy strategies. METHODS Fellows surveyed a convenience sample (19/91) of public health veterinarians at CDC to identify veterinary workforce recruitment and retention problems faced by federal agencies; responses were categorized into themes. A focus group (20/91) of staff veterinarians subsequently prioritized the categorized themes from least to most important. Participants identified activities to address the three recruitment concerns with the highest combined weight. RESULTS Participants identified the following three highest prioritized problems faced by federal agencies when recruiting veterinarians to public health: (1) lack of awareness of veterinarians' contributions to public health practice, (2) competitive salaries, and (3) employment and training opportunities. Similarly, key concerns identified regarding retention of public health practice veterinarians included: (1) lack of recognition of veterinary qualifications, (2) competitive salaries, and (3) seamless integration of veterinary and human public health. CONCLUSIONS Findings identified multiple barriers that can affect recruitment and retention of veterinarians engaged in public health practice. Next steps should include replicating project efforts among a national sample of public health veterinarians. A committed and determined long-term effort might be required to sustain initiatives and policy proposals to increase U.S. veterinary public health capacity.


title: Predictors of Emergency Preparedness and Compliance.

text: BACKGROUND:: In response to the evolving nature of potential disasters, both human made and natural, this research identifies predictors of individual emergency preparedness and compliance with government requests. METHODS:: A survey of a nationally representative sample of US adults (1629 respondents) revealed which emergency supplies and plans they had in place; their perceived level of preparedness and that of their local health care system; the likelihood of 7 terrorist and 4 naturally occurring events, whether they would evacuate their home; shelter in place at home and work; be quarantined, vaccinated, or take medication; and whether they believed that these actions would increase their chances for survival. RESULTS:: Having supplies was predicted by being male, older, wealthier, and white, living in the western United States, and being exposed to national news. Having plans was related to living in the western United States, having children, and being exposed to national news. Compliance was associated with being female and ill. Holding demographic factors constant, preparedness and compliance with government requests were associated with the perceived likelihood of a natural but not a terrorist event, the perceived efficacy of requested actions, and belief in one's local health care system. CONCLUSIONS:: A focus on natural as opposed to terrorist events and people's perceived efficacy of emergency actions and local health care systems may increase their preparedness and compliance with government requests.


title: Running interference: prospects and obstacles to using small interfering RNAs as small molecule drugs.

text: RNA interference (RNAi) is a well-conserved, ubiquitous, endogenous mechanism that uses small noncoding RNAs to silence gene expression. The endogenous small RNAs, called microRNAs, are processed from hairpin precursors and regulate important genes involved in cell death, differentiation, and development. RNAi also protects the genome from invading genetic elements, encoded by transposons and viruses. When small double-stranded RNAs, called small interfering (si)RNAs, are introduced into cells, they bind to the endogenous RNAi machinery to disrupt the expression of mRNAs containing complementary sequences with high specificity. Any disease-causing gene and any cell type or tissue can potentially be targeted. This technique has been rapidly utilized for gene-function analysis and drug-target discovery and validation. Harnessing RNAi also holds great promise for therapy, although introducing siRNAs into cells in vivo remains an important obstacle. Pilot siRNA clinical studies began just three years after the discovery that RNAi works in mammalian cells. This review discusses recent progress and obstacles to using siRNAs as small molecule drugs.


title: Selection of molecular descriptors with artificial intelligence for the understanding of HIV-1 protease peptidomimetic inhibitors-activity.

text: Quantitative Structure Activity Relationship (QSAR) techniques are used routinely by computational chemists in drug discovery and development to analyze datasets of compounds. Quantitative numerical methods like Partial Least Squares (PLS) and Artificial Neural Networks (ANN) have been used on QSAR to establish correlations between molecular properties and bioactivity. However, ANN may be advantageous over PLS because it considers the interrelations of the modeled variables. This study focused on the HIV-1 Protease (HIV-1 Pr) inhibitors belonging to the peptidomimetic class of compounds. The main objective was to select molecular descriptors with the best predictive value for antiviral potency (Ki). PLS and ANN were used to predict Ki activity of HIV-1 Pr inhibitors and the results were compared. To address the issue of dimensionality reduction, Genetic Algorithms (GA) were used for variable selection and their performance was compared against that of ANN. Finally, the structure of the optimum ANN achieving the highest Pearson's-R coefficient was determined. On the basis of Pearson's-R, PLS and ANN were compared to determine which exhibits maximum performance. Training and validation of models was performed on 15 random split sets of the master dataset consisted of 231 compounds. For each compound 192 molecular descriptors were considered. The molecular structure and constant of inhibition (Ki) were selected from the NIAID database. Study findings suggested that non-covalent interactions such as hydrophobicity, shape and hydrogen bonding describe well the antiviral activity of the HIV-1 Pr compounds. The significance of lipophilicity and relationship to HIV-1 associated hyperlipidemia and lipodystrophy syndrome warrant further investigation.


title: [Development of peptidic MERS-CoV entry inhibitors].

text: In 2012, a new SARS-like coronavirus emerged in the Middle East, namely the Middle East respiratory syndrome coronavirus (MERS-CoV). It has caused outbreaks with high mortality. During infection of target cell, MERS-CoV S protein S1 subunit binds to the cellular receptor (DPP4), and its S2 subunit HR1 and HR2 regions intact with each other to form a stable six-helix bundle to mediate the fusion between virus and target cell membranes. Hence, blocking the process of six-helix bundle formation can effectively inhibit MERS-CoV entry into the target cells. This review focuses on the recent advance in the development of peptidic entry inhibitors targeting the MERS-CoV S2 subunit.


title: HLA class I antigen serves as a receptor for human coronavirus OC43.

text: Human coronaviruses are associated with acute respiratory and enteric disease in man as such their target cells are probably the epithelial cells lining the respiratory and enteric tract. Attachment of virus to specific receptors on the cell surface is a major determinant of virus tropism in pathogenesis (1). Recently, aminopeptidase-N was identified as a cell receptor for the 229e coronavirus (2). Cell receptor(s) for OC43 coronavirus have not been identified. However, it is of pathologic significance that OC43 virus shares DNA sequence homology with the two coronavirus isolates, SK and SD, from the brain of patients with multiple sclerosis (MS) (3). Probing MS and control brain with probes specific for human, murine, porcine and bovine coronavirus by in situ hybridization resulted in the detection of coronavirus RNA in 12 of 22 MS brain samples; five of which were positive with the OC43 probe (4). A study of virus-ligand interactions of OC43 with human rhabdomyosarcoma (RD) cells, which are highly susceptible to virus infection, was undertaken to identify possible cell receptors. The binding of virus collected from the supernatant of infected cells to cell proteins immobilized on nitrocellulose paper was used to screen for virus-ligand interactions. The next step was the identification or development of antibodies to each of the ligands, and to test their ability to blockade receptor activity by culturing infected cells in medium containing the ligand antibodies and measuring the effect on virus yield. The preliminary experiments reported here reveal an interesting observation of strong affinity of OC43 virus for the HLA class I antigen.


INtENsiVE CaRE.


title: Recent advances in the use of intrinsic fluorescence for bacterial identification and characterization.

text: Live bacteria contain a variety of intracellular biomolecules that have specific excitation and emission wavelength spectra characterizing their intrinsic fluorescence. This paper reviews recent developed methods using bacterial intrinsic fluorescence for identification and characterization purposes. Potential applications of such methods at the industrial level are also addressed.


title: [Preparation and identification of monoclonal antibodies against SARS-CoV putative protein X4].

text: OBJECTIVE To obtain monoclonal antibodies against putative protein X4 of SARS-CoV for further study of the structure and function of protein X4. METHODS Balb/c mice were immunized with recombinant Protein X4, hybridoma cell lines secreting monoclonal antibodies against protein X4 were screened by regular cell fusion and subcloning approach. The specificities of these monoclonal antibodies were determined by Western blotting and Immunofluorescence assay. RESULTS Three hybridoma cell lines (8A5, 8H6 and 4A2) stable in secreting specific monoclonal antibodies were successfully obtained. They could bind specifically to protein X4 proved by Western blotting. All of them belonged to the IgG2a isotype proved by antigen mediated ELISA. Indirect Immunofluorescence assay indicated that they could specifically bind to protein X4 expressed in SARS-CoV infected Vero E6 cells. CONCLUSION Monoclonal antibodies of high specificity against protein X4 have been successfully prepared, which laid the foundation for the further study of protein X4.


title: Common whiplash: psychosomatic or somatopsychic?

text: One hundred and seventeen randomly selected patients were assessed for different psychological variables (personality traits, wellbeing, and cognitive ability) in relation to somatic symptoms after common whiplash. Patients were investigated at an average of 7.4 (SD 4.2) days after trauma and again at three and six months. The course of recovery could not be explained by the patients' disposition. The results indicated that improvement in wellbeing was associated with recovery from somatic symptoms. There was, however, cognitive impairment in patients who suffered from symptoms. These findings support the view that the psychological and cognitive problems of patients with common whiplash are mainly related to somatic symptoms.


Legal foundations of the fight against COVID- 19.


title: Activation of p90 ribosomal S6 kinase by ORF45 of Kaposi's sarcoma-associated herpesvirus and its role in viral lytic replication.

text: The extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway is essential for infection by a variety of viruses. The p90 ribosomal S6 kinases (RSKs) are direct substrates of ERK and functional mediators of ERK MAPK signaling, but their roles in viral infection have never been examined. We demonstrate that ORF45 of Kaposi's sarcoma-associated herpesvirus (KSHV) interacts with RSK1 and RSK2 and strongly stimulates their kinase activities. The activation of RSK by ORF45 is correlated with ERK activation but does not require MEK. We further demonstrate that RSK1/RSK2 is activated during KSHV primary infection and reactivation from latency; a subset of RSK1/RSK2 is present in the viral replication compartment in the nucleus. Depletion of RSK1/RSK2 by small interfering RNA or the specific inhibitor BI-D1870 suppresses KSHV lytic gene expression and progeny virion production, suggesting an essential role of RSK1/RSK2 in KSHV lytic replication.


Heterogeneity of subgenomic mRNAs of a mutant mouse hepatitis virus strain JHM2C.


Dermatology in the time of SARS.


title: Recombinant bovine adenovirus type 3 expressing bovine viral diarrhea virus glycoprotein E2 induces an immune response in cotton rats.

text: Recombinant bovine adenovirus is being developed as a live vector for animal vaccination and for human gene therapy. In this study, two replication-competent bovine adenovirus 3 (BAV-3) recombinants (BAV331 and BAV338) expressing bovine viral diarrhea virus (BVDV) glycoprotein E2 in the early region 3 (E3) of BAV-3 were constructed. Recombinant BAV331 contains chemically synthesized E2 gene (nucleotides modified to remove internal cryptic splice sites) under the control of BAV-3 E3/major late promoter (MLP), while recombinant BAV338 contains original E2 gene under the control of human cytomegalovirus immediate early promoter. Since E2, a class I membrane glycoprotein, does not contain its own signal peptide sequence at the 5' end, the bovine herpesvirus 1 (BHV-1) glycoprotein D signal sequence was fused in frame to the E2 open reading frame (ORF) for proper processing of the E2 glycoprotein in both the recombinant viruses. Recombinant E2 protein expressed by BAV331 and BAV338 recombinant viruses was recognized by E2-specific monoclonal antibodies as a 53-kDa protein, which also formed dimer with an apparent molecular weight of 94 kDa. Insertion of an E2-expression cassette in the E3 region did not effect the replication of recombinant BAV-3s. Intranasal immunization of cotton rats with these recombinant viruses generated E2-specific IgA and IgG responses at the mucosal surfaces and in the serum. In summary, these results show that the pestivirus glycoprotein can be expressed efficiently by BAV-3. In addition, mucosal immunization with replication-competent recombinant bovine adenovirus 3 can induce a specific immune response against the expressed antigen.


title: [Assessment of Chemotherapy-Induced Adverse Events Using a Sharing System of Patient-Reported Information via a Touch Panel].

text: Screening for total pain and sharing of patient information including adverse events for patients receiving chemotherapy by medical staff is needed in clinical practice. We introduced a sharing system for patient-oriented outcome sheets via a touch panel at an outpatient chemotherapy clinic. This study aimed to assess whether the system contributes to the improved management of treatment-related adverse events. We retrospectively analyzed data from a total of 215 patients at Ehime University Hospital using their electronic medical records from April to August 2015. Forty of these patients had received interventions relating to treatment-related adverse events. The proportion of a total number of interventions before and after the sharing system was 42/282(14.9%)and 45/215(20.9%), respectively. The proportion of a total number of interventions at the first course of outpatient chemotherapy also increased from 9/40(22.5%)to 14/40(35%)compared with before the sharing system. The purpose of interventions were for insomnia, anorexia, and cancer-related pain, etc., listed in order of degree of frequency. These results suggest that a sharing system of patient-reported interview sheets contributes to tracking treatment -related adverse events and aids in ensuring interventions can be efficiently performed by multidisciplinary team members.


title: [ 'Severe acute respiratory syndrome' (SARS) in perspective].

text: In the Netherlands, the risk of an outbreak of the severe acute respiratory syndrome (SARS) appears to be limited, if people in contact with a possibly imported case observe strict measures to prevent contamination. SARS may well be a zoonosis. Bovine spongiform encephalopathy and outbreaks of virus infections in the bioindustry, such as swine fever, foot-and-mouth disease and classical avian influenza, have led to massive killing of cattle, swine and fowl in the Netherlands. The possibility that the bioindustry constitutes a risky microbiological 'experiment' makes a discussion as to its future in the Netherlands urgent.


WHO says SARS outbreak is over, but fight should go on.


title: Comparison of two real-time quantitative assays for detection of severe acute respiratory syndrome coronavirus.

text: The new severe acute respiratory syndrome (SARS) coronavirus (CoV), described in February 2003, infected a total of 8,439 people. A total of 812 people died due to respiratory insufficiency. Close contact with symptomatic patients appeared to be the main route of transmission. However, potential transmission by blood transfusion could not be definitely excluded. Two real-time SARS-specific PCR assays were assessed for their sensitivities, agreement of test results, and intra-assay variabilities. Both assays rely on reverse transcription and amplification of extracted RNA. Dilutions of gamma-irradiated cell culture supernatants of SARS CoV-infected Vero E6 cells were prepared to determine the precisions, linear ranges, and accuracies of the assays. The linear range for the Artus RealArt HPA-Coronavirus assay (Artus assay) was 1 x 10(2) to 1 x 10(7) copies/ml, and that for the Roche LightCycler SARS CoV Quantification kit (Roche assay) was 1 x 10(4) to 2 x 10(8) copies/ml. The detection limit of the Roche assay was 3,982.1 copies/ml, whereas that of the Artus assay was 37.8 copies/ml. Detection limits were calculated with a standard preparation that was recommended for use by the World Health Organization. However, quantification of CoV in this preparation may be imprecise. In summary, both assays are suitable for quantitative measurement of SARS CoV at the high concentrations expected in sputum samples. The Artus assay is also suitable for detection of SARS CoV at the low concentrations found in serum samples.


title: SARS: What We Have Learned So Far ...

text: This article addresses severe acute respiratory syndrome (SARS), which was first identified in November of 2002 and continued to spread till 2003. The article briefly covers the pathogenesis of SARS followed by a review of current epidemiological and empirical data on this new disease. Information on signs and symptoms of SARS as well as the current suggested treatment will be presented.


title: Sequence comparison of porcine respiratory coronavirus isolates reveals heterogeneity in the S, 3, and 3-1 genes.

text: Four new porcine respiratory coronavirus (PRCV) isolates were genetically characterized. Subgenomic mRNA patterns and the nucleotide sequences of the 5' ends of the S genes, the open reading frame (ORF) 3/3a genes, and the ORF 3-1/3b genes of these PRCV isolates were determined and compared with those of other PRCV and transmissible gastroenteritis virus (TGEV) isolates. The S, ORF 3/3a, and ORF 3-1/3b genes are under intense study because of their possible roles in determining tissue tropism and virulence. Northern (RNA) blot analysis of subgenomic mRNAs revealed that mRNA 2, which encodes for the S gene, of the PRCV isolates migrated faster than the mRNA 2 of TGEV. The PRCV isolates AR310 and LEPP produced eight subgenomic mRNA species, the same number as produced by the virulent Miller strain of TGEV. However, the PRCV isolates IA1894 and ISU-1 produced only seven subgenomic mRNA species. All four of the PRCV isolates were found to have a large in-frame deletion in the 5' end of the S gene; however, the size and location of the deletion varied. Analysis of the ORF 3/3a gene nucleotide sequences from the four PRCV isolates also showed a high degree of variability in this area. The ORF 3 gene of the PRCV isolates AR310 and LEPP was preceded by a CTAAAC leader RNA-binding site, and the ORF 3 gene was predicted to yield a protein of 72 amino acids, the same size as that of the virulent Miller strain of TGEV. The PRCV isolates AR310 and LEPP are the first PRCV isolates found to have an intact ORF 3 gene. The ORF 3a gene of the PRCV isolate IA1894 was preceded by a CTAAAC leader RNA-binding site and was predicted to yield a truncated protein of 54 amino acids due to a 23-nucleotide deletion. The CTAAAC leader RNA-binding site and ATG start codon of ORF 3 gene of the PRCV isolate ISU-1 were removed because of a 168-nucleotide deletion. Analysis of the ORF 3-1/3b gene nucleotide sequences from the four PRCV nucleotides isolates also showed variability.


title: Neuro-Mechanics of Recumbent Leg Cycling in Post-Acute Stroke Patients.

text: Cycling training is strongly applied in post-stroke rehabilitation, but how its modular control is altered soon after stroke has been not analyzed yet. EMG signals from 9 leg muscles and pedal forces were measured bilaterally during recumbent pedaling in 16 post-acute stroke patients and 12 age-matched healthy controls. Patients were asked to walk over a GaitRite mat and standard gait parameters were computed. Four muscle synergies were extracted through nonnegative matrix factorization in healthy subjects and patients unaffected legs. Two to four synergies were identified in the affected sides and the number of synergies significantly correlated with the Motricity Index (Spearman's coefficient = 0.521). The reduced coordination complexity resulted in a reduced biomechanical performance, with the two-module sub-group showing the lowest work production and mechanical effectiveness in the affected side. These patients also exhibited locomotor impairments (reduced gait speed, asymmetrical stance time, prolonged double support time). Significant correlations were found between cycling-based metrics and gait parameters, suggesting that neuro-mechanical quantities of pedaling can inform on walking dysfunctions. Our findings support the use of pedaling as a rehabilitation method and an assessment tool after stroke, mainly in the early phase, when patients can be unable to perform a safe and active gait training.


title: Application of Fluorescent Cholangiography for Determination of the Resection Line During a Single-Incision Laparoscopic Cholecystectomy for a Benign Lesion of the Cystic Duct: Preliminary Experience.

text: BACKGROUND To avoid bile leakage from the stump of a cystic duct that is closed at edematous and/or involved areas, the decision regarding the location of the resection line during a laparoscopic cholecystectomy for benign lesions extending into the cystic duct is important and requires technical ingenuity. For these situations, we used fluorescent cholangiography. METHODS Our procedure for single-incision laparoscopic cholecystectomy utilized the SILS-Port, and an additional pair of 5-mm forceps was inserted via an umbilical incision. As a fluorescence source, 1 mL of indocyanine green was intravenously injected after endotracheal intubation of patients in the operating room. A laparoscopic fluorescence imaging system developed by Karl Storz Endoskope was utilized for fluorescent cholangiography. RESULTS Fluorescent cholangiography could be used to identify the border of the lesion in the cystic duct. According to the fluorescent cholangiography results, a location for the resection line of the cystic duct could be identified; therefore, the planned resection was successful and produced a histologically negative margin. CONCLUSIONS Application of fluorescent cholangiography in the determination of the location of the resection line location during a laparoscopic cholecystectomy for benign lesions of the cystic duct should be widely accepted.


title: Colonic stenosis post-necrotizing enterocolitis in term newborn with acquired cytomegalovirus infection.

text: Necrotizing enterocolitis is a gastrointestinal emergency typical of premature infants. Intestinal strictures infrequently complicate medical or surgical treatment of necrotizing enterocolitis. Postnatal cytomegalovirus infection with gastrointestinal linvolvement has occasionally been described in subjects with necrotizing enterocolitis. We report the case of a full term infant presenting necrotizing enterocolitis, acquired cytomegalovirus infection and post necrotizing enterocolitis colonic stricture.List of abbreviations: necrotizing enterocolitis = NEC,cytomegalovirus = CMV.