title: Non-major histocompatibility complex-restricted cytotoxicity of bovine coronavirus-infected target cells mediated by bovine intestinal intraepithelial leukocytes.

text: Non-specific cellular mechanisms of defence against intestinal virus infections of cattle were investigated using bovine coronavirus (BCV) as a representative enteric virus. Since BCV infection is limited to the epithelial cells of the intestinal tract, defence mechanisms must be capable of acting at that site to be effective. Therefore, the intraepithelial leukocyte (IEL) population of the intestinal mucosa was chosen for initial study. Treatment of intestinal samples with DTT and EDTA in calcium- and magnesium-free buffers allowed recovery of viable IEL populations appropriate for further functional assessment. Studies of IELs isolated from neonatal calves revealed that non-major histocompatibility complex (MHC)-restricted cytotoxicity of BCV-infected target cells was more prevalent in calves with concurrent virus infection, suggesting in vivo activation of the cytotoxic response. Peripheral blood mononuclear cells from the same calves did not mediate cytotoxicity, emphasizing the difference in function of lymphocytes isolated from different anatomical sites. IELs from normal adult animals rarely showed spontaneous non-MHC-restricted cytotoxicity. However, interleukin-2 (IL-2) was a potent activator of IEL cytotoxicity in vitro, enhancing the killing of BCV-infected target cells after just 18 h of treatment. Incubation of IELs with interferon-gamma and tumour necrosis factor (TNF) did not induce cytotoxic activity, but TNF could augment the levels of IL-2-induced cytotoxicity. Although further analysis of the cytotoxic effector cells present in the intestinal epithelium is required, the present study indicates that the IEL population may play a role in enteric antiviral activity.


title: Comparison of equine arteritis virus isolates using neutralizing monoclonal antibodies and identification of sequence changes in GL associated with neutralization resistance.

text: Three murine monoclonal antibodies (MAbs) that neutralize equine arteritis virus (EAV) infectivity were identified and characterized. The antibodies, 93B, 74D(B) and 38F, recognized the major envelope glycoprotein (GL) encoded by open reading frame (ORF) 5 in immunoblots and by immunoprecipitation. All three MAbs were used to compare the Bucyrus isolate of EAV and MAb neutralization-resistant (NR) escape mutants with the vaccine virus and 19 independent field isolates of EAV by virus neutralization. The different abilities of the MAbs to neutralize virus isolates indicated that they recognize non-identical epitopes. Susceptibility to virus neutralization could not be used to distinguish viruses from acutely and persistently infected horses. Comparison of the ORF 5 nucleotide and deduced amino acid sequence from NR and neutralization-sensitive virus isolates revealed amino acid sequence changes at positions 99 and 100 which correlate with the NR phenotype. Additional unique changes in the amino acid sequence of MAb NR viruses at positions 96 and 113 may also contribute to neutralization resistance. The sequence data further showed that the Bucyrus-derived viruses contain one N-glycosylation site, whereas the field isolates DL8 and DL11 possess two sites, both of which are used. Most of the non-conservative amino acid sequence changes were located within the second half of the N-terminal hydrophilic domain. Sequence changes within the first half of the N-terminal ectodomain, the predicted transmembrane domain and the C-terminal hydrophilic domain were mainly silent base substitutions or resulted in conservative amino acid substitutions, suggesting that these regions of the protein are functionally conserved.


title: [Clinical features of children with SARS-CoV-2 infection: an analysis of 13 cases from Changsha, China].

text: OBJECTIVE To study the clinical features of children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS A retrospective analysis was performed for the clinical data of 13 children with SARS-CoV-2 infection who hospitalized in a Changsha hospital. RESULTS All 13 children had the disease onset due to family aggregation. Of the 13 children, 2 had no symptoms, and the other 11 children had the clinical manifestations of fever, cough, pharyngeal discomfort, abdominal pain, diarrhea, convulsions, or vomiting. As for clinical typing, 7 had mild type, 5 had common type, and 1 had severe type. The median duration of fever was 2 days in 6 children. All 13 children had normal levels of peripheral blood lymphocyte counts, immunoglobulins, CD4, CD8, and interleukin-6. The median time to clearance of SARS-CoV-2 was 13 days in the nasopharyngeal swabs of the 13 children. Three children presented false negatives for RT-PCR of SARS-CoV-2. SARS-CoV-2 RNA remained detectable in stools for 12 days after the nasopharyngeal swab test yielded a negative result. Abnormal CT findings were observed in 6 children. All 13 children were cured and discharged and they were normal at 2 weeks after discharge. CONCLUSIONS Intra-family contact is the main transmission route of SARS-CoV-2 infection in children, and there is also a possibility of fecal-oral transmission. Mild and common types are the major clinical types in children with SARS-CoV-2 infection, and cytokine storm is not observed. Children with SARS-CoV-2 infection tend to have a good short-term prognosis, and follow-up is needed to observe their long-term prognosis. Multiple nucleic acid tests should be performed for patients with SARS-CoV-2 infection and their close contacts by multiple site sampling.


title: Correlation between Chest Computed Tomography Scan Findings and Mortality of COVID-19 Cases; a Cross sectional Study.

text: Introduction Predicting the outcomes of COVID-19 cases using different clinical, laboratory, and imaging parameters is one of the most interesting fields of research in this regard. This study aimed to evaluate the correlation between chest computed tomography (CT) scan findings and outcomes of COVID-19 cases. Methods This cross sectional study was carried out on confirmed COVID-19 cases with clinical manifestations and chest CT scan findings based on Iran's National Guidelines for defining COVID-19. Baseline and chest CT scan characteristics of patients were investigated and their correlation with mortality was analyzed and reported using SPSS 21.0. Results 380 patients with the mean age of 53.62 ± 16.66 years were evaluated (66.1% male). The most frequent chest CT scan abnormalities were in peripheral (86.6%) and peribronchovascular interstitium (34.6%), with ground glass pattern (54.1%), and round (53.6%) or linear (46.7%) shape. There was a significant correlation between shape of abnormalities (p = 0.003), CT scan Severity Score (CTSS) (p <0.0001), and pulmonary artery CT diameter (p = 0. 01) with mortality. The mean CTSS of non-survived cases was significantly higher (13.68 ± 4.59 versus 8.72 ± 4.42; <0.0001). The area under the receiver operating characteristic (ROC) curve of CTSS in predicting the patients' mortality was 0.800 (95% CI: 0.716-0.884). The best cut off point of chest CTSS in this regard was 12 with 75.82% (95% CI: 56.07%-88.98%) sensitivity and 75.78% (95% CI: 70.88%-80.10%) specificity. The mean main pulmonary artery diameter in patients with CTSS ≥ 12 was higher than cases with CTSS < 12 (27.89 ± 3.73 vs 26.24 ± 3.14 mm; p < 0.0001). Conclusion Based on the results of the present study it seems that there is a significant correlation between chest CT scan characteristics and mortality of COVID-19 cases. Patients with lower CTSS, lower pulmonary artery CT diameter, and round shape opacity had lower mortality.


title: [Fatal swine influenza A H1N1 and Mycoplasma pneumoniae coinfection in a child].

text: One of the most common causes of death in influenza patients is secondary bacterial pneumonia and the most common pathogens involved are Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenza. To diagnose co infection with bacteria in a H1N1 case can be difficult but should be strongly suspected in a child who present with influenza like illness and lower respiratory tract signs or symptoms. We report coinfection of Mycoplasma pneumoniae in swine influenza A H1N1 child who presented with extensive pneumonia and expired within 48 hours.


title: Intermittent pneumatic compression. A comparison of femoral vein velocity with five different devices.

text: AIM Different mechanical devices for thromboprophylaxis have different flow characteristics. A new device (Vadoplex) has been developed to provide a short impulse around the calf, a concept derived from the efficacy of foot impulse technology. New devices should be compared with existing devices to establish whether it has a comparable ability to augment venous velocity. Objectives of the study were to compare the venous velocity induced by the Vadoplex with established intermittent pneumatic calf and leg compressors (Covidien and Huntleigh). METHODS The venous velocity was established in ten healthy volunteers with standardised Duplex ultraonography of the common femoral vein. Measurements were taken at rest and on standing, with each device inactive and active. RESULTS The Vadoplex induced an increased femoral venous velocity at least as enhanced as established calf and full leg sleeves. CONCLUSION Calf impulse technology is an alternative to other systems in enhancing femoral vein blood flow, itself a surrogate for assumed thromboprophylactic effect.


title: [Differential diagnosis of severe acute respiratory syndrome (SARS) in "post-SARS" stage].

text: The epidemic of severe acute respiratory syndrome (SARS) has now been brought under control and entered the so-called post-SARS stage, with only a very few new cases reported daily throughout China. As an infectious disease spreading through the respiratory tract, SARS is featured by the inconsistency between its clinical representations, physical signs of the lungs and chest imaging findings. It has been shown that atypical pneumonia (AP), with similar clinical features to SARS, has been identified in Guangzhou, China, long before the prevalence of SARS, a fact that urges further understanding of SARS in regard to its incidence and variable clinical courses, for its differential diagnosis with such diseases as AP, influenza-related pneumonia, pulmonary tuberculosis, fungal and cytomegalovirus pneumonia. Information sharing among the medical institutes and training of the first-line medical staff for their better understanding and awareness of SARS and AP is crucial in the clinical practice, to insure timely case identification and avoid "oversensitive" diagnosis. Consultation of particular cases involving experts from multiple medical science fields should be encouraged, which is also an effective measure against newly emerged infectious diseases.


title: Astonishing diversity of natural surfactants: 5. Biologically active glycosides of aromatic metabolites.

text: This review article presents 342 aromatic glycosides, isolated from and identified in plants and microorganisms, that demonstrate different biological activities. They are of great interest, especially for the medicinal and/or pharmaceutical industries. These biologically active natural surfactants are good prospects for the future chemical preparation of compounds useful as antioxidant, anticancer, antimicrobial, and antibacterial agents. These glycosidic compounds have been classified into several groups, including simple aromatic compounds, stilbenes, phenylethanoids, phenylpropanoids, naphthalene derivatives, and anthracene derivatives.


Uncommon mediastinal cyst-like manifestation of feline infectious peritonitis.


title: Antigenic relationships of coronaviruses detectable by plaque neutralization, competitive enzyme linked immunoabsorbent assay, and immunoprecipitation.

text: The antigenic relationships of mouse coronaviruses JHM and A59, human viruses OC43 and 229E, and multiple sclerosis (MS) isolates SD and SK have been investigated by plaque neutralization, competitive enzyme linked immunoabsorbent assay, and immunoprecipitation. A59, SK, or SD plaques are neutralized by antiserum prepared against homologous as well as heterologous virus. Plaque neutralization also demonstrated weak reactivity between SD or SK and mouse virus JHM but no reactivity with human coronavirus 229E. An antiserum prepared against human virus OC43 neutralized viruses SD and SK but not mouse viruses A59 or JHM. In a competitive enzyme linked immunoabsorbent assay (cELISA) the binding of antiserum prepared against MS isolate SK to bound SK antigen was inhibited to a comparable degree using OC43, SD, or A59 viral antigens. Coronavirus 229E or uninfected cell antigens did not block the binding of anti-SK serum to bound antigen. However, a cELISA utilizing OC43 as bound antigen and competing an anti-OC43 serum suggests that virus OC43 may be more closely related to SK than A59. Specific viral polypeptides that share antigenic determinants have been identified by immunoprecipitation of S35 methionine labeled viral infected cell extracts. Polypeptides of similar molecular weight were precipitated from A59, SD, or SK infected cell extracts by SD, SK, OC43, or A59 antisera. Our data suggests that the mouse coronavirus A59, human coronavirus OC43, and MS isolates SD and SK contain antigenically related polypeptides of similar molecular weight.


title: Minimise calf diarrhoea by good husbandry: treat sick calves by fluid therapy.

text: Calf morbidity and mortality rates up to three weeks old were 11.3% and 1.2% respectively when good husbandry was practised compared with 36.6% and 5.4% with poor husbandry. The annual mortality rate was 4% in earlier years when management was inadequate. The main features of good husbandry were feeding at least 2.25 litres of colostrum to each calf within the first hour of life to boost its immunity while minimising infection rates by regular thorough cleaning and disinfection of calving boxes and calf pens and providing uncrowded, dry, draught free accommodation. By these means satisfactory control of early calf losses was achieved without concentrating on specific microorganisms. Detailed examinations of sacrificed moribund diarrhoeic calves showed that E. coli, cryptosporidia, rota and corona viruses were associated agents. The serum immunoglobulin level of any individual calf was an unreliable guide to its future viability because 12 out of 488 calves with high levels died whereas 53 with unacceptably low levels remained healthy. Nevertheless when calves were grouped by immunoglobulin status the highest mortality rates occurred among those with low levels. Clinical examination of diarrhoeic calves to determine the degree of dehydration was more reliable than clinical pathologic laboratory tests. Results of a treatment trial indicated that oral glucose-glycine electrolyte solution alone was as beneficial as the electrolyte plus an oral triple sulphonamide and streptomycin. This was not unexpected in view of the widespread antibiotic resistance also demonstrated.


title: [RISK ASSESSMENT FOR AEROSOL INFECTION BY THE NEW CORONA VIRUS AND PROTECTION BY RESPIRATORS].

text: INTRODUCTION SARS-CoV-2 is dispersed from patients by talking, coughing and sneezing. The generated micro-droplets aerosols can travel up to 8 meters, stay suspended for long periods and preserve viral infectivity for a median of 2.7 hours. An unprotected person exposed to this cloud, might inhale a considerable amount of infectious viral doses, which will attach to the ACE 2 receptors on alveoli epithelium, resulting in infection. N95 respirators and surgical masks block 95% and 50-60% respectively of inhalable particles and protect the wearer from infection. Surgical masks and N95 without exhalation valve, protect both the wearer and the environment from carriers and sick people.


title: Why are acute ischemic stroke patients not receiving IV tPA? Results from a national registry.

text: OBJECTIVE To determine patient and hospital characteristics associated with not providing IV tissue plasminogen activator (tPA) to eligible patients with acute ischemic stroke (AIS) in clinical practice. METHODS We performed a retrospective cohort study of patients with AIS arriving within 2 hours of onset to hospitals participating in Get With The Guidelines-Stroke without documented contraindications to IV tPA from April 2003 through December 2011, comparing those who received tPA to those who did not. Multivariable generalized estimating equation logistic regression modeling identified factors associated with not receiving tPA. RESULTS Of 61,698 eligible patients with AIS presenting within 2 hours of onset (median age 73 years, 51% female, 74% non-Hispanic white, median NIH Stroke Scale score 11, interquartile range 6-18), 15,282 (25%) were not treated with tPA within 3 hours. Failure to give tPA decreased over time from 55% in 2003 to 2005 to 18% in 2010 to 2011 (p < 0.0001). After adjustment for all covariates, including stroke severity, factors associated with failure to treat included older age, female sex, nonwhite race, diabetes mellitus, prior stroke, atrial fibrillation, prosthetic heart valve, NIH Stroke Scale score <5, arrival off-hours and not via emergency medical services, longer onset-to-arrival and door-to-CT times, earlier calendar year, and arrival at rural, nonteaching, non-stroke center hospitals located in the South or Midwest. CONCLUSIONS Overall, about one-quarter of eligible patients with AIS presenting within 2 hours of stroke onset failed to receive tPA treatment. Thrombolysis has improved dramatically over time and is strongly associated with stroke center certification. Additionally, some groups, including older patients, milder strokes, women, and minorities, may be undertreated.


title: Association of New Putative Epitopes of Myelin Proteolipid Protein (58-74) with Pathogenesis of Multiple Sclerosis.

text: Multiple sclerosis (MS) is an autoimmune disease in which auto-reactive T cells react with self-antigens expressed in the central nervous system (CNS). The main cause of MS is unknown. Nonetheless, the most probable theory is based on molecular mimicry, which suggests that some infections can activate T cells against brain auto-antigens like myelin proteolipid protein (PLP) and initiate the disease cascade. This study is conducted to evaluate the activatory effects of PLP58-74 on T lymphocytes and humoral immunity. PLP58-74 was considered as an immunodominant epitope candidate of PLP using bioinformatics tools. Patients and healthy individuals' peripheral blood mononuclear cells (PBMCs) were treated with PLP58-74 and its proliferative effects were evaluated through assessing proliferating cell nuclear antigen (PCNA) gene expression changes by real time PCR and immunocytochemistry assay. Finally, the rate of CD4+ and CD8+ T cells were assessed by flowcytometry. ELISA was also performed to measure anti PLP58-74 antibody in patients' serum. PLP58-74 induced proliferation in patients' PBMCs while it did not influence PBMCs of healthy individuals. CD4+ T cells were the main activated cells in reaction to PLP58-74 which increased from 22% to 39.91%. In addition, immune assay showed threefold increase in specific anti PLP58-74 IgG in patients compared to healthy controls. Results showed that PLP58-74 can stimulate CD4+ T cells and humoral immunity. Therefore it seems that the epitopes of some microorganisms mimicking PLP such as PLP58-74 might have a potential role in the initiation of MS.


title: Severe community-acquired pneumococcal pneumonia (CAP) - a potentially fatal illness.

text: Two cases of severe community-acquired pneumococcal pneumonia (CAP) admitted to our hospital within 24 h are described, both in young males. These two cases illustrate the usefulness of the British Thoracic Society severity criteria and serve to emphasize the importance of early recognition of adverse physiology in critically ill patients. We should not lose sight of the continued impact of pneumonia in this climate of widespread fear about severe acute respiratory syndrome (SARS).


title: Minimal sequence and structural requirements of a subgenomic RNA promoter for turnip crinkle virus.

text: Infection of plants or protoplasts with turnip crinkle virus (TCV) results in the synthesis of the genomic RNA and two subgenomic (sg) RNAs of 1.7 kb and 1.45 kb, respectively. Both of the sgRNA promoters were characterized previously and their secondary structures predicted by computer analysis [J. Wang and A. E. Simon (1997). Virology 232, 174-186]. Secondary structure-sensitive chemical and enzymatic probes have now been used to determine the structure of the promoter directing synthesis of the 1.45-kb sgRNA, namely the 1.45-kb sgRNA promoter, in solution. The newly obtained structure conforms with the previously predicted hairpin structure except for the hairpin base: four CG base pairs and a CA bulge are present instead of an A bulge. Studies of deletions within the 96-nucleotide (nt) 1.45-kb sgRNA promoter defined a minimal 30-nt core sequence as essential for promoter activity: a 21-nt hairpin and a 9-nt flanking single-stranded sequence. Mutational analysis in the stem section of the core promoter supported a role for the primary sequence and secondary structure in promoter activity. Sequence alterations in the flanking single-stranded region further suggest that the sequence CCCAUUA, encompassing the transcription start site, is required for efficient transcription of the 1.45-kb sgRNA by the TCV RNA-dependent RNA polymerase in vivo.


title: Management of diarrhoea in HIV-infected patients.

text: Human immunodeficiency virus (HIV) infection can weaken the immune system causing its inability to combat opportunistic infections. Managing the complexity of these opportunistic infections has created a challenge for healthcare professionals. Our knowledge on the aetiological agents causing opportunistic infections in immunocompromised hosts has increased over the last decade. Diarrhoeal diseases are frequent complications associated with HIV-infected patients. For most of the causes of diarrhoea, the clinical signs are non-specific, and the laboratory diagnostic workup is neither easy nor fast. This review provides data on aetiological approaches of common diarrhoeal diseases including viral, microbacterial, parasitic, bacterial and fungal infections, and HIV enteropathy; diagnostic evaluation; and treatment of diarrhoea in HIV-infected patients. This article will be helpful for those who are in the practice of managing diarrhoea in such patients.


title: Embracing the Power of Show-Me ECHO Learning Communities to Transform Clinical Practice in Missouri.

text: Show-Me ECHO, a state-funded project, provides access to education within a community of learners in order to optimize healthcare for the citizens of Missouri. Through videoconferencing and case-based review, ECHO shifts professional development from learning about medical problems in isolation to experiential learning as part of a multidisciplinary team. The establishment of a statewide COVID-19 ECHO is allowing a rapid response to this novel, unprecedented, and unanticipated health care crisis. There are many ongoing opportunities for clinicians from across the state to join a Show-Me ECHO learning community as a means to elevate their practice and improve ability to respond amidst a constantly evolving health care environment.


title: Avian bornavirus is present in many tissues of psittacine birds with histopathologic evidence of proventricular dilatation disease.

text: Proventricular dilatation disease (PDD) is a neurologic disease of psittacine birds suspected to be caused by a recently identified Avian bornavirus (ABV). In the current report, data supporting the causal association of ABV with PDD are presented. Immunohistochemistry (IHC) with rabbit polyclonal antiserum raised against ABV nucleocapsid protein was used to identify cell and organ distribution of viral antigen. The ABV antigen was most consistently detected in brain, spinal cord, adrenal gland, pancreas, and kidney. Histopathologic evaluation was correlated with ABV-specific polymerase chain reaction (PCR) and immunohistochemical tests in multiple tissues from 16 psittacine birds with and without PDD. Using histopathologic diagnosis as the gold standard, the sensitivity and specificity of IHC for ABV antigens were found to be 100% and 100%, respectively. Many more tissues were positive for ABV RNA by reverse transcription PCR than were positive for pathologic changes or viral antigens by IHC, indicating the presence of subclinical or asymptomatic infection at many sites.


title: Influence of substituent ribose on transition state affinity in reactions catalyzed by adenosine deaminase.

text: Adenosine deaminase from calf intestine hydrolyzes adenine at a limiting rate four orders of magnitude lower than that for adenosine, while Km values for these substrates are about the same (Wolfenden, R., et al. (1969), Biochemistry 8, 2412-2415). Reactivity of 6-substituents, toward nucleophilic displacement, is found to be affected only slightly by removal of ribose as a 9-substituent, in model reactions. Substituent ribose thus appears to stabilize, selectively, the transition state for enzymatic deamination. In contrast with the small influence of substituent ribose on the apparent binding affinity of substrates, removal of substituent ribose from a potential transition state analogue, 1,6-dihydro-6-hydroxy-methylpurine ribonucleoside, results in a lowering of its affinity for the enzyme by several orders of magnitude. The synthesis of the analogue and related compounds is described, and their properties compared with those of other photoadducts and of the naturally occurring inhibitors covidarabine and coformycin. Binding of these inhibitors is found to result in the appearance of ultraviolet-absorbing bands in the neighborhood of 323 nm.


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title: Does biodiversity protect humans against infectious disease?

text: Control of human infectious disease has been promoted as a valuable ecosystem service arising from the conservation of biodiversity. There are two commonly discussed mechanisms by which biodiversity loss could increase rates of infectious disease in a landscape. First, loss of competitors or predators could facilitate an increase in the abundance of competent reservoir hosts. Second, biodiversity loss could disproportionately affect non-competent, or less competent reservoir hosts, which would otherwise interfere with pathogen transmission to human populations by, for example, wasting the bites of infected vectors. A negative association between biodiversity and disease risk, sometimes called the "dilution effect hypothesis," has been supported for a few disease agents, suggests an exciting win-win outcome for the environment and society, and has become a pervasive topic in the disease ecology literature. Case studies have been assembled to argue that the dilution effect is general across disease agents. Less touted are examples in which elevated biodiversity does not affect or increases infectious disease risk for pathogens of public health concern. In order to assess the likely generality of the dilution effect, we review the association between biodiversity and public health across a broad variety of human disease agents. Overall, we hypothesize that conditions for the dilution effect are unlikely to be met for most important diseases of humans. Biodiversity probably has little net effect on most human infectious diseases but, when it does have an effect, observation and basic logic suggest that biodiversity will be more likely to increase than to decrease infectious disease risk.


title: Retrospective study of 46 cases of feline haemobartonellosis in Israel and their relationships with FeLV and FIV infections.

text: Forty-six cats with clinical haemobartonellosis were studied; 75 per cent of the cats of known age were two-and-a-half years old or younger, 50 per cent were intact males and 19.5 per cent were castrated males. The predominant signs of the disease were tachypnoea, lethargy, depression, anorexia, infestation with fleas, pale mucous membranes, icterus, emaciation, dehydration, splenomegaly, anaemia, leucocytosis, increased activities of alanine aminotransferase and aspartate aminotransferase, and azotaemia. Thirty-eight per cent of the cats that were tested for feline leukaemia virus (FeLV) antigen were positive, and 22 per cent of those tested for feline immunodeficiency virus (FIV) antibodies were positive. The prevalence of both FeLV and FIV was much higher than in the general Israeli cat population. The cats infected with both Haemobartonella felis and FeLV had a significantly lower body temperature, were more anaemic and the mean cell volume of their erythrocytes was greater than in the cats with haemobartonellosis alone.


title: Downstream sequences influence the choice between a naturally occurring noncanonical and closely positioned upstream canonical heptameric fusion motif during bovine coronavirus subgenomic mRNA synthesis.

text: Mechanisms leading to subgenomic mRNA (sgmRNA) synthesis in coronaviruses are poorly understood but are known to involve a heptameric signaling motif, originally called the intergenic sequence. The intergenic sequence is the presumed crossover region (fusion site) for RNA-dependent RNA polymerase (RdRp) during discontinuous transcription, a process leading to sgmRNAs that are both 5' and 3' coterminal. In the bovine coronavirus, the major fusion site for synthesis of mRNA 5 (GGUAGAC) does not conform to the canonical motif (UC[U,C]AAAC) at three positions (underlined), yet it lies just 14 nucleotides downstream from such a sequence (UCCAAAC). The infrequently used canonical sequence, by computer prediction, is buried within the stem of a stable hairpin (-17.2 kcal/mol). Here we document the existence of this stem by enzyme probing and examine its influence and that of neighboring sequences on the unusual choice of fusion sites by analyzing transcripts made in vivo from mutated defective interfering RNA constructs. We learned that (i) mutations that were predicted to unfold the stem-loop in various ways did not switch RdRp crossover to the upstream canonical site, (ii) a totally nonconforming downstream motif resulted in no measurable transcription from either site, (iii) the canonical upstream site does not function ectopically to lend competence to the downstream noncanonical site, and (iv) altering flanking sequences downstream of the downstream noncanonical motif in ways that diminish sequence similarity with the virus genome 5' end caused a dramatic switch to the upstream canonical site. These results show that sequence elements downstream of the noncanonical site can dramatically influence the choice of fusion sites for synthesis of mRNA 5 and are interpreted as being most consistent with a mechanism of similarity-assisted RdRp strand switching during minus-strand synthesis.


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.


docid: mrdbrkqt

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.


docid: pusqumrf

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].


docid: iykbkgop

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.


docid: awodygou

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.