title: SARS, MERS and coronavirus infections.

text: The human coronavirus (HCoV) contains HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV- HKU1, SARS-CoV and MERS-CoV. HCoV-229E, HCoV-NL63, HCoV-OC43 and HCoV-HKU1 are pathogens of common cold. During 2002-2003, a new coronavirus, the SARS-CoV, was found to be the cause of an acute, severe frequently fatal respiratory disease with prominent systemic symptoms (severe acute respiratory syndrome). The outbreak originated in south- ern China, probably following transmission from an animal in animal markets or bats to hu- mans. In 2012, some cases of novel coronavirus infection were reported in Arabian Peninsula with pneumonia and acute kidney injury. This novel coronavirus has been named Middle East respiratory syndrome coronavirus (MERS-CoV). The virus probably has come from camels and bats. I describe here about coronaviruses that have wide disease spectrum.from common colds to severe fatal illness as emerging infectious diseases.


title: Public health in Canada: a difficult history.

text: Although the outbreak of severe acute respiratory syndrome in 2003 was the event that focused attention on Canada's capacity in public health, there have been, and will be, many other public health challenges, not just in the form of outbreaks but of a diverse set of threats to health, both infectious and non-infectious. Like many other countries, Canada must face the challenge of building and sustaining the capacity to respond to this broad range of challenges. Recently, there has been an emphasis on strengthening the public health infrastructure, including inter-jurisdictional agreements, research, knowledge translation, information systems and the workforce.


title: [Clinical features of 96 patients with severe acute respiratory syndrome from a hospital outbreak].

text: OBJECTIVE To describe a hospital outbreak of severe acute respiratory syndrome (SARS) and summarize the clinical features and therapeutic approaches. METHODS Clinical data in this cohort were collected prospectively as they were identified. RESULTS The outbreak started with a SARS patient from the community on 30 January 2003, followed by a total of 96 people [76 women and 20 men; mean age (29.5 +/- 10.3) years; 93.8% of whom were health care workers] infected in a short period of time after their exposure to this source patient. The incubation period ranged from 1 to 20 days, with a mean of (5.9 +/- 3.5) days. The initial temperature was (38.3 +/- 0.6) degrees C, while the highest was (39.2 +/- 0.6) degrees C (P < 0.001), with a mean fever duration of (9.0 +/- 4.2) days. Other common symptoms included fatigue, cough, mild sputum production, chills, headache, general malaise and myalgia. The radiographic changes were predominantly bilateral and in the middle or lower lung zones. Leukopenia was observed in 67.7% of this cohort. The mean lowest oxygen saturation was (94.8 +/- 3.1)% with supplementary oxygen through a nasal cannula. 68.8% of the patients were treated with methylprednisolone for a mean period l of (4.9 +/- 2.4) days. The initial dose was (67.3 +/- 28.2) mg/d and the maximal dose was (82.4 +/- 30.5) mg/d. Ninety-five patients (99.0%) had a complete clinical recovery, and 1 patient died of progressive acute respiratory distress syndrome. The mean hospitalized duration was (17.2 +/- 8.0) days. CONCLUSION SARS appears to be highly contagious and potentially lethal among health care workers, characterized by acute onset and rapid progression. Corticosteroids, antibiotics, human gamma-globulin, interferon-alpha, and antiviral drugs, although used empirically, might be of some benefits in shortening the clinical course.


title: Microbiology of calf diarrhoea in southern Britain.

text: Faeces samples from calves with diarrhoea in 45 outbreaks were examined for six enteropathogens. Rotavirus and coronavirus were detected by ELISA in 208 (42 per cent) and 69 (14 per cent) of 490 calves respectively; calici-like viruses were detected by electron microscopy in 14 of 132 calves (11 per cent). Cryptosporidium were detected in 106 of 465 (23 per cent), Salmonella species in 58 of 490 (12 per cent) and enterotoxigenic Escherichia coli bearing the K99 adhesin (K99+ E coli) in nine of 310 calves (3 per cent). In the faeces of 20 per cent of calves with diarrhoea more than one enteropathogen was detected; in 31 per cent no enteropathogen was found. Faces samples from 385 healthy calves in the same outbreaks were also examined. There was a significant statistical association of disease with the presence of rotavirus, coronavirus, Cryptosporidium and Salmonella species (P less than 0.001). Healthy calves were not examined for calici-like viruses and the association of K99+ E coli with disease was not analysed because there were too few positive samples. Rotavirus infections were more common in dairy herds and single suckler beef herds whereas Salmonella infections were more often found in calf rearing units. Cryptosporidium were more common in single and multiple suckler beef herds. K99+ E coli were found in one dairy herd and one multiple suckler beef herd both with unhygienic calving accommodation. Variations in coronavirus detection among different farm types were not statistically significant. In this survey rotavirus was the most commonly detected agent in calf diarrhoea and Cryptosporidium were found in approximately one quarter of affected calves. Infection with Salmonella species was widespread, but K99+ E coli infections were less common in the United Kingdom than in other countries.


title: From SARS to 2009 H1N1 influenza: the evolution of a public health incident management system at CDC.

text: The organization of the response to infectious disease outbreaks by public health agencies at the federal, state, and local levels has historically been based on traditional public health functions (e.g., epidemiology, surveillance, laboratory, infection control, and health communications). Federal guidance has established a framework for the management of domestic incidents, including public health emergencies. Therefore, public health agencies have had to find a way to incorporate traditional public health functions into the common response framework of the National Incident Management System. One solution is the development of a Science Section, containing public health functions, that is equivalent to the traditional incident command system sections. Public health agencies experiencing difficulties in developing incident management systems should consider the feasibility and suitability of creating a Science Section to allow a more seamless and effective coordination of a public health response, while remaining consistent with current federal guidance.


Coronavirus (COVID-19) Pandemic and Radical Cystectomy.


title: Association of host tropism of Middle East syndrome coronavirus with the amino acid structure of host cell receptor dipeptidyl peptidase 4.

text: The Middle East syndrome coronavirus (MERS-CoV) is a recently emerging betacoronavirus with high fatality. Recently, dipeptidyle peptidase (CD26, DPP4) was identified as the host cell receptor for MERS-CoV. Interestingly, despite of common presence of DPP4 receptors the binding and infection of various cells shows imminent variability. In this report, we provide a tool for prediction of the host tropism of the virus based on the host receptor binding interface. We found out that, in the binding of MERS-CoV to cells the amino acid residues in lancets 4 and 5 of DPP4 receptor, namely K267, Q286, T288, R317, R336, Q344 A291, L294, and I295 are involved. Changes in these residues correspond to profound decrease in virus binding to cells. The nine residues at the interface between the virus spikes and the lancets 4 and 5 of host DPP4 can be used as a predictive tool for the host tropism and virus affinity to host cell receptors.


title: [Frequency and etiology of calf losses and calf diseases before weaning in cow-calf farms. II. Microbiological and parasitological diagnoses in diarrheic calves].

text: Diarrhea is the most frequently diagnosed disease in Swiss cow-calf farms. During an longitudinal study conducted in 105 cow-calf farms in Switzerland in 1993-95, blood and fecal samples were collected from diarrheic calves and from calves that died because of diarrhea. Campylobacter spp. were detected in 42%, E. coli (VTEC) in 32%, rotavirus in 33%, coronavirus in 13%, coccidia in 43% and helminths in 8% of the cases. In some samples Yersinia pseudotuberculosis were isolated. The BVD-virus antigen was not detected in any of the calves examined. In most cases concurrent infection with several enteropathogens was diagnosed. Specific causes of diarrhea were therefore difficult to establish. The bacteriological findings of this study have implication for food safety: VTEC, Campylobacter spp. Yersinia spp. and cryptosporidia are considered as potential causes on zoonoses.


title: Rationally-designed vaccine adjuvants: separating efficacy from toxicity.

text: Adjuvants, substances included in many vaccines in order to improve immune responses, are challenging to develop and license because adjuvant compounds that stimulate strong protective immunity also frequently induce significant toxicity. Adjuvant design and development has until recently been largely empirical; but with the current knowledge that most adjuvants act via receptors of the innate immune system, molecular-based approaches are rapidly advancing the field. Data support the concept that proinflammatory pathways induced by innate immune receptor triggering underlie many of the observed toxic effects. Importantly, the cellular signaling pathways that lead to inflammation are known, for a number of innate immune receptors, to be distinct from those that are involved in the costimulation of protective adaptive immune responses, leading to approaches for attenuating inflammatory signaling that should lead to safer and more effective vaccine adjuvants. This article addresses whether there is a clear rationale for the separation of toxicity from efficacy in the function of adjuvants based upon innate immune receptor ligands.


title: Development of monoclonal antibody ELISA for simultaneous detection of bovine coronavirus, rotavirus serogroup A, and Escherichia coli K99 antigen in feces of calves.

text: A rapid ELISA was developed for simultaneous detection of bovine coronavirus (BCV), rotavirus (RV) serogroup A, and Escherichia coli K99 antigen in feces of calves. A mixture of 3 monoclonal antibodies specific for BCV, RV, or K99 was used successfully to capture the antigens; the same antibodies labeled with peroxidase were used to detect BCV, RV, or K99. The triple ELISA was compared with standard reference diagnostic methods by examining feces from experimentally and naturally infected and healthy calves. All the components of the test were highly specific (greater than 90%) and sensitive (BCV, 77%; K99, 93%; RV, 100%) when used in a format requiring short incubation steps at 20 C and visual recording of results.


docid: hijusalj

title: Measurement of subgroups of peripheral blood T lymphocytes in patients with severe acute respiratory syndrome and its clinical significance.

text: OBJECTIVE To investigate the changes of subgroups of peripheral blood T lymphocytes in patients with severe acute respiratory syndrome (SARS) and its clinical significance. METHODS Subgroups of blood T lymphocytes in 93 patients with SARS were detected by flow cytometer. The results detected in 64 normal subjects and 50 patients with AIDS served as controls. RESULTS The numbers of CD(3)(+), CD(4)(+), and CD(8)(+) lymphocytes all significantly decreased in acute phase of patients with SARS [(722 +/- 533)/microliter, (438 +/- 353)/microliter, (307 +/- 217)/microliter] compared with those in normal controls [(1527 +/- 470)/microliter, (787 +/- 257)/microliter, (633 +/- 280)/microliter, all P <0.01], which was different from what we observed in patients with AIDS who had decreased CD(4)(+) [(296 +/- 298)/microliter] but increased CD(8)(+) [(818 +/- 566)/microliter] counts. The counts of CD(3)(+), CD(4)(+), and CD(8)(+) lymphocytes decreased more apparently in patients with severe SARS. All the five patients who died had CD(4)(+) counts less than 200/microliter. As the patients' condition improved, CD(3)(+), CD(4)(+), and CD(8)(+) counts gradually returned to normal ranges. CONCLUSION The damage of cellular immunity is probably an important mechanism of pathogenesis of SARS.


title: Epidemiology of respiratory viral infection using multiplex rt-PCR in Cheonan, Korea (2006-2010).

text: Multiplex RT-PCR was used to detect respiratory viruses in 5,318 clinical samples referred to the laboratory of a tertiary teaching hospital from December 2006 to November 2010. The acquired data were analyzed with respect to types, ratio, and co-infection trends of infected respiratory viruses. Trends in respiratory viral infection according to sex, age, and period of infection were also analyzed. Of the 5,318 submitted clinical samples, 3,350 (63.0%) specimens were positive for at least one respiratory virus. The infection rates were 15.8% for human rhinovirus, 14.4% for human respiratory syncytial virus A, 9.7% for human respiratory syncytial virus B, 10.1% for human adenovirus, 5.4% for influenza A virus, 1.7% for influenza B virus, 4.7% for human metapneumovirus, 2.3% for human coronavirus OC43, 1.9% for human coronavirus 229E/NL63, 3.7% for human parainfluenza virus (HPIV)-1, 1.1% for HPIV-2, and 5.3% for HPIV-3. The co-infection analysis showed 17.1% of double infections and 1.8% of triple infections. The median age of virus-positive patients was 1.3 years, and 91.5% of virus-positive patients were under 10 years old. Human respiratory syncytial virus was the most common virus in children under 5 years of age, and the influenza A virus was the most prevalent virus in children over 5 years of age. These results help in elucidating the tendency of respiratory viral infections.


Decline in microbial studies for patients with pulmonary infections.


title: Mass casualty respiratory care: a discussion of issues of interest.

text: This Journal conference was the first to be held with a live audience. After the final faculty presentation, and in lieu of a conference summary from the guest editors, the conference faculty had a discussion session that addressed written questions from the audience. The moderators, Lewis Rubinson and Rich Branson, reviewed the questions and addressed them either to specific conference faculty or to the entire conference faculty group. There were too many questions to address in the allotted time, so the moderators selected the questions they thought either most pertinent or most likely to be answerable.


title: Feline infectious peritonitis: a worldwide serosurvey.

text: Feline sera from 13 countries were assayed for coronavirus antibody, using a heterologous indirect immunofluorescence test. Significantly higher percentages of antibody carriers were obtained during testing randomly collected sera from mature males (greater than 1 year old) than in testing females of the same age. Antibodies were infrequently found in immature cats (less than 6 months old); at 1 year of age or older, a plateau was reached and little change in the percentage of seroconverted animals was observed. Differences were not detected between purebred cats vs mixed-breed cats or household vs stray cats. In animals showing clinical signs of feline infection peritonitis (FIP), antibodies were encountered with higher frequency than in clinically healthy cats. Significant differences in antibody incidence were found between countries, with a range between less than 10% and greater than 50% of seropositive individuals. Antibodies were detected in sera from an isolated cat population (Marion Island) and from wild-caught cheetahs (Acinonyx jubatus). The antibody specificity for FIP virus was confirmed by neutralization tests. The antibody pattern in randomly collected solitary cats, in catteries, and cats with clinical FIP showed characteristic differences in titer and incidence. The implications of these results for the epizootiology of FIP are discussed.


docid: klmimnbl

title: Mode of membrane interaction and fusogenic properties of a de novo transmembrane model peptide depend on the length of the hydrophobic core.

text: Model peptides composed of alanine and leucine residues are often used to mimic single helical transmembrane domains. Many studies have been carried out to determine how they interact with membranes. However, few studies have investigated their lipid-destabilizing effect. We designed three peptides designated KALRs containing a hydrophobic stretch of 14, 18, or 22 alanines/leucines surrounded by charged amino acids. Molecular modeling simulations in an implicit membrane model as well as attenuated total reflection-Fourier transform infrared analyses show that KALR is a good model of a transmembrane helix. However, tryptophan fluorescence and attenuated total reflection-Fourier transform infrared spectroscopy indicate that the extent of binding and insertion into lipids increases with the length of the peptide hydrophobic core. Although binding can be directly correlated to peptide hydrophobicity, we show that insertion of peptides into a membrane is determined by the length of the peptide hydrophobic core. Functional studies were performed by measuring the ability of peptides to induce lipid mixing and leakage of liposomes. The data reveal that whereas KALR14 does not destabilize liposomal membranes, KALR18 and KALR22 induce 40 and 50% of lipid-mixing, and 65 and 80% of leakage, respectively. These results indicate that a transmembrane model peptide can induce liposome fusion in vitro if it is long enough. The reasons for the link between length and fusogenicity are discussed in relation to studies of transmembrane domains of viral fusion proteins. We propose that fusogenicity depends not only on peptide insertion but also on the ability of peptides to destabilize the two leaflets of the liposome membrane.


title: Seroprevalence of Bartonella henselae infection and correlation with disease status in cats in Switzerland.

text: The prevalence of infection with Bartonella henselae was investigated in cats from different areas of Switzerland. Serum samples of 728 cats were examined for antibodies to B. henselae by immunofluorescent antibody testing, and the results were analyzed with a view to a possible correlation between a positive titer and signalment, clinical signs, infection with feline leukemia virus (FeLV), feline immunodeficiency virus (FIV), feline coronavirus (FCoV), or feline spumavirus (FeSFV), and the living environments of the cats. The seroprevalence in all cats was 8.3%. No significantly different prevalence was found in sick versus healthy cats (9.2 versus 7.2%); however, in sick cats seropositive for B. henselae, there was an increased frequency of stomatitis and a variety of diseases of the kidneys and the urinary tract. There was an increased prevalence of B. henselae in cats positive for FCoV (P = 0.0185) or FeSFV (P = 0.0235) and no statistically significant increased prevalence in cats infected with FeLV or FIV. There was no correlation between a positive titer and sex or breed. The same prevalence of B. henselae antibodies was found in cats with and without access to the outdoors and in cats from single- and multicat households. The seroprevalence was increased in cats living south of the Alps (12.1%); however, this difference was not significant (P = 0.0616).


title: Cell-mediated immunity against turkey coronaviral enteritis (bluecomb).

text: Studies on cell-mediated immune response in turkeys infected with turkey coronavirus (TCV) were made. A whole blood culture technique was developed for quantitatively evaluating in vitro lymphocyte reactivity to mitogens concanavalin A, phytohemagglutinin-P, and TCV antigen. The degree of blastogenesis was quantitated by the measurement of the uptake of the [125I]deoxyuridine in the presence of fluorodeoxyuridine. The stimulation indices were consistently higher in the infected birds compared with those in the noninfected controls, and they were statistically significant (P < 0.05). The detection of TCV specific responses indicated that cell-mediated immunity may be important in determining the immunity against turkey coronaviral enteritis. The whole blood lymphocyte transformation assay was emphasized as a convenient and useful in vitro indicator of cell-mediated immunity in TCV infection.


title: Tropical malabsorption.

text: Malabsorption is an important clinical problem both in visitors to the tropics and in native residents of tropical countries. Infections of the small intestine are the most important cause of tropical malabsorption. Protozoal infections cause malabsorption in immunocompetent hosts, but do so more commonly in the setting of immune deficiency. Helminth infections occasionally cause malabsorption or protein-losing enteropathy. Intestinal tuberculosis, chronic pancreatitis and small-bowel bacterial overgrowth are important causes of tropical malabsorption. In recent years, inflammatory bowel disease and coeliac disease have become major causes of malabsorption in the tropics. Sporadic tropical sprue is still an important cause of malabsorption in adults and in children in South Asia. Investigations to exclude specific infective, immunological or inflammatory causes are important before considering tropical sprue as a diagnosis. This article briefly reviews the management of tropical sprue and presents an algorithm for its investigation and management.


docid: ahzfzjqs

title: The fusion activity of HIV-1 gp41 depends on interhelical interactions.

text: Infection by human immunodeficiency virus type I requires the fusogenic activity of gp41, the transmembrane subunit of the viral envelope protein. Crystallographic studies have revealed that fusion-active gp41 is a "trimer-of-hairpins" in which three central N-terminal helices form a trimeric coiled coil surrounded by three antiparallel C-terminal helices. This structure is stabilized primarily by hydrophobic, interhelical interactions, and several critical contacts are made between residues that form a deep cavity in the N-terminal trimer and the C-helix residues that pack into this cavity. In addition, the trimer-of-hairpins structure has an extensive network of hydrogen bonds within a conserved glutamine-rich layer of poorly understood function. Formation of the trimer-of-hairpins structure is thought to directly force the viral and target membranes together, resulting in membrane fusion and viral entry. We test this hypothesis by constructing four series of gp41 mutants with disrupted interactions between the N- and C-helices. Notably, in the three series containing mutations within the cavity, gp41 activity correlates well with the stability of the N-C interhelical interaction. In contrast, a fourth series of mutants involving the glutamine layer residue Gln-653 show fusion defects even though the stability of the hairpin is close to wild-type. These results provide evidence that gp41 hairpin stability is critical for mediating fusion and suggest a novel role for the glutamine layer in gp41 function.


title: Diagnosis of a critical respiratory illness caused by human metapneumovirus by use of a pan-virus microarray.

text: A pan-virus DNA microarray (Virochip) was used to detect a human metapneumovirus (hMPV) strain associated with a critical respiratory tract infection in an elderly adult with chronic lymphocytic leukemia. This infection had previously eluded diagnosis despite extensive microbiological testing for possible etiologic agents. The patient's hMPV strain did not grow in viral culture, and only one of five specific reverse transcription-PCR assays for hMPV was positive.


docid: psqhorjh

title: Molecular and biological characterization of human monoclonal antibodies binding to the spike and nucleocapsid proteins of severe acute respiratory syndrome coronavirus.

text: Human monoclonal antibodies (MAbs) were selected from semisynthetic antibody phage display libraries by using whole irradiated severe acute respiratory syndrome (SARS) coronavirus (CoV) virions as target. We identified eight human MAbs binding to virus and infected cells, six of which could be mapped to two SARS-CoV structural proteins: the nucleocapsid (N) and spike (S) proteins. Two MAbs reacted with N protein. One of the N protein MAbs recognized a linear epitope conserved between all published human and animal SARS-CoV isolates, and the other bound to a nonlinear N epitope. These two N MAbs did not compete for binding to SARS-CoV. Four MAbs reacted with the S glycoprotein, and three of these MAbs neutralized SARS-CoV in vitro. All three neutralizing anti-S MAbs bound a recombinant S1 fragment comprising residues 318 to 510, a region previously identified as the SARS-CoV S receptor binding domain; the nonneutralizing MAb did not. Two strongly neutralizing anti-S1 MAbs blocked the binding of a recombinant S fragment (residues 1 to 565) to SARS-CoV-susceptible Vero cells completely, whereas a poorly neutralizing S1 MAb blocked binding only partially. The MAb ability to block S1-receptor binding and the level of neutralization of the two strongly neutralizing S1 MAbs correlated with the binding affinity to the S1 domain. Finally, epitope mapping, using recombinant S fragments (residues 318 to 510) containing naturally occurring mutations, revealed the importance of residue N479 for the binding of the most potent neutralizing MAb, CR3014. The complete set of SARS-CoV MAbs described here may be useful for diagnosis, chemoprophylaxis, and therapy of SARS-CoV infection and disease.


Information Diet in Covid-19 Crisis; a Commentary.


title: Are nidoviruses hijacking the autophagy machinery?

text: Autophagy is an intracellular catabolic transport route conserved among all eukaryotic cells. It has multiple important physiological functions, one of which is to act as an immune mechanism against intracellular microbes.(1,2) Bacteria and viruses targeted for destruction are sequestered into large double-membrane vesicles called autophagosomes and subsequently delivered to the lysosomes where they are consumed by resident hydrolases. Unfortunately, conserved cellular pathways are often exploited by pathogens to facilitate their entry or replication, and autophagy is no exception. It has become clear that certain bacteria and viruses subvert this process to their advantage.(3) Nidoviruses, which comprise coronaviruses and arteriviruses, might be among the successful. Long recognized as the cause of veterinary infections, this group of enveloped, positive-stranded RNA viruses is currently of considerable interest due to the emergence of new human coronaviruses, especially the severe acute respiratory syndrome (SARS)-coronavirus. In this mini-review, we will summarize the so far limited number of studies that have demonstrated that double-membrane vesicles resembling autophagosomes are the sites of nidovirus replication. In addition, we will discuss how the formation of these large vesicles might be induced.


title: Increased proteolytic activity and matrix metalloprotease expression in lungs during infection by porcine reproductive and respiratory syndrome virus.

text: The local increase in the secretion of extracellular proteases, allowing cleavage of the extracellular matrix and thereby facilitating the infiltration of T cells, monocytes and neutrophils, is a hallmark of chronic inflammation and autoimmunity. In pulmonary genetic diseases, such as emphysema and cystic fibrosis, proteases can also favour the development of local immunodeficiency by degrading key regulators of the immune response, such as CD4, CD8, IgG, ICAM-1 and C3b receptors. Since several infectious agents can give rise to severe pulmonary disorders associated with opportunistic infections, we sought to determine whether an increase in proteolytic activity occurred during infection with porcine reproductive and respiratory syndrome virus (PRRSV), the causative agent of a new disease in swine characterized by severe respiratory problems in young pigs. Piglets were infected with the virus and bronchoalveolar lavages were collected at various times post-infection to measure the net proteolytic activity. It was shown that PRRSV infection leads to a significant increase in proteolytic activity in pulmonary fluids. Maximal activity was found at 7 and 14 days post-infection, with a return towards normal levels at day 42. Zymographic analyses showed a significant increase in the secretion of matrix metalloproteases (MMPs) 2 and 9, two enzymes involved in tissue remodelling. Histological analyses showed a correlation between the increase in proteolytic activity and the appearance of lesions that were characterized by massive lymphomononuclear cell infiltration. These results suggest that virus infection of the lungs can lead to a transient increase in proteolytic activity that could favour opportunistic infection.


Immune response in Balb/c mice induced by recombinant spike protein of severe acute respiratory syndrome coronavirus.


title: Characterization of a unique group-specific protein (U122) of the severe acute respiratory syndrome coronavirus.

text: A novel coronavirus (CoV) has been identified as the etiological agent of severe acute respiratory syndrome (SARS). The SARS-CoV genome encodes the characteristic essential CoV replication and structural proteins. Additionally, the genome contains six group-specific open reading frames (ORFs) larger than 50 amino acids, with no known homologues. As with the group-specific genes of the other CoVs, little is known about the SARS-CoV group-specific genes. SARS-CoV ORF7a encodes a putative unique 122-amino-acid protein, designated U122 in this study. The deduced sequence contains a probable cleaved signal sequence and a C-terminal transmembrane helix, indicating that U122 is likely to be a type I membrane protein. The C-terminal tail also contains a typical endoplasmic reticulum (ER) retrieval motif, KRKTE. U122 was expressed in SARS-CoV-infected Vero E6 cells, as it could be detected by Western blot and immunofluorescence analyses. U122 is localized to the perinuclear region of both SARS-CoV-infected and transfected cells and colocalized with ER and intermediate compartment markers. Mutational analyses showed that both the signal peptide sequence and ER retrieval motif were functional.


title: Diurnal variation in the symptoms of colds and influenza.

text: The present research examined diurnal variation in the severity of symptoms of experimentally-induced colds and influenza. Nasal secretion was greatest in the morning, decreased over the day, and then showed a slight increase in the late evening. Colds did not change the average temperature, nor did they alter the temperature rhythm. Similar, negative results were found with alertness ratings. Influenza B illnesses produced an increase in nasal secretion and systemic effects. The average temperature increased during this illness and subjects reported that they felt more drowsy. Diurnal variation in the severity of local and central symptoms was observed, with nasal secretion and the temperature increase being greatest in the early morning. These results have important implications for the assessment and treatment of the illnesses.


[When you are sick].


title: Functional Neurologic Outcomes Change Over the First 6 Months After Cardiac Arrest.

text: OBJECTIVES To determine the longitudinal changes in functional outcome and compare ordinal outcome scale assessments in comatose cardiac arrest survivors. DESIGN Prospective observational study of comatose cardiac arrest survivors. Subjects who survived to 1 month were included. SETTING Academic medical center ICU. PATIENTS Ninety-eight consecutive patients who remained comatose after resuscitation from cardiac arrest; 45 patients survived to 1 month. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Patients' functional neurologic outcomes were assessed by phone call or in-person clinic visit at 1, 3, 6, and 12 months postcardiac arrest using the modified Rankin Scale, Glasgow Outcome Scale, and Barthel Index. A "good" outcome was defined as modified Rankin Scale 0-3, Barthel Index 70-100, and Glasgow Outcome Scale 4-5. Changes in dichotomized outcomes and shifts on each outcome scale were analyzed. The mean age of survivors was 51 ± 19 years and 18 (40%) were women. Five (19%) out of 26 patients with data available at all timepoints improved to good modified Rankin Scale outcome and none worsened to poor outcome between postarrest months 1 and 6 (p = 0.06). Thirteen patients (50%) improved on the modified Rankin Scale by 1-3 points and four (15%) worsened by 1-2 points between months 1 and 6 (overall improvement by 0.5 points; 95% CI, 0-1; p = 0.04). From postarrest months 6 to 12, there was no change in the number of patients with good versus poor outcomes. The modified Rankin Scale and Barthel Index were more sensitive to detecting changes in outcome than the Glasgow Outcome Scale. CONCLUSIONS In initially comatose cardiac arrest survivors, improvements in functional status occur over the first 6 months after the event. There was no significant change in outcome between postarrest months 6 and 12. The modified Rankin Scale is a sensitive outcome scale in this population.


title: Rapid de novo aneurysm formation after clipping of a ruptured middle cerebral artery aneurysm in an infant with an MYH11 mutation.

text: The authors report the case of a previously healthy 6-month-old girl who presented with right arm and leg stiffening consistent with seizure activity. An initial CT scan of the head demonstrated acute subarachnoid hemorrhage in the basal cisterns extending into the left sylvian fissure. Computed tomography angiography demonstrated a 7 × 6 × 5-mm saccular aneurysm of the inferior M2 division of the left middle cerebral artery. The patient underwent left craniotomy and microsurgical clip ligation with wrapping of the aneurysm neck because the vessel appeared circumferentially dysplastic in the region of the aneurysm. Postoperative angiography demonstrated a small remnant, sluggish distal flow, but no significant cerebral vasospasm. Fifty-five days after the initial aneurysm rupture, the patient presented again with an acute intraparenchymal hemorrhage of the left anterior temporal lobe. Angiogram revealed a circumferentially dysplastic superior division of the M2 branch, with a new 5 × 4-mm saccular aneurysm distinct from the first, with 2 smaller aneurysms distal to the new ruptured aneurysm. Endovascular parent vessel occlusion with Onyx was performed. Genetic testing revealed a mutation of the MYH11. To the authors' knowledge, this is the first report of rapid de novo aneurysm formation in an infant with an MYH11 mutation. The authors review the patient's clinical presentation and management and comprehensively review the literature on this topic.


Provision of Service During the Covid-19 Pandemic


title: Tonsillectomy healing.

text: OBJECTIVES We performed a prospective observation study in an outpatient surgical and office setting to compare human post-tonsillectomy healing to human cutaneous wound healing and to established animal models of oral healing. METHODS Fourteen teenaged patients underwent planned tonsillectomy. Intraoral digital photographs were collected at the time of tonsillectomy, during the management of complications, and at postoperative office visits. Serial intraoral photographs of one patient were taken at 48-hour intervals from the time of surgery until postoperative day 17. RESULTS Intraoral photographs from the days after tonsillectomy revealed a pattern of inflammation and healing that closely paralleled that in human skin and in canine and porcine oral wound models. CONCLUSIONS Edema and pain are greatest immediately after surgery, probably as a result of thermal effects and expression of inflammatory mediators that stimulate pharyngeal nociceptors. Pain gradually decreases over time, with an increase in analog pain measures on postoperative days 3 to 5 corresponding to the maximal wound inflammation documented in experimental models. Epithelial ingrowth beneath a fibrin clot begins shortly after wounding. Separation of the fibrin clot about 7 days after surgery exposes vascular stroma. Involution of the vascular stroma and completion of epithelial coverage correlate with decreased pain levels and a lessened risk of bleeding.


title: Bridging distance and culture with a cyberspace method of qualitative analysis.

text: This article describes a qualitative research method that weds the cyberspace technology of e-mail with a phenomenological research approach. Examples are provided from 2 separate data sets. One data set explored the meaning of health for Japanese elders; the second explored Chinese nurses' experience of taking care of patients with severe acute respiratory syndrome. Lessons learned while using the cyberspace method are discussed, including guidance for organizing a long-distance research team, the central place of trust, and the time when e-mail communication demands to be supplemented with face-to-face interaction. The potential for bridging distance and culture with this cyberspace method is introduced for consideration and critique.


title: Subcellular localization of herpes simplex virus type 1 UL51 protein and role of palmitoylation in Golgi apparatus targeting.

text: The herpes simplex virus type 1 (HSV-1) UL51 gene products are virion-associated phosphoproteins with apparent molecular masses of 27, 29, and 30 kDa in HSV-1-infected cells. In this study, we have investigated the intracellular localization and distribution of UL51 protein both in infected cells and in transfected cells expressing only UL51. We found that this protein colocalized closely with Golgi marker proteins such as the Golgi-58K protein and GM130 in transfected cells expressing only UL51. However, in infected cells, the UL51 protein localized to the juxtanuclear region but only partially colocalized with the Golgi maker proteins. Mutant protein analysis revealed that the N-terminal 15 amino acid residues of the UL51 protein sufficed for this Golgi localization property. The UL51 protein redistributed on addition of brefeldin A. This was prevented by pretreatment with 2-deoxyglucose and sodium azide, which results in ATP depletion, but not by pretreatment with NaF and AlCl(3), which activates heterotrimeric G proteins. Moreover, we found that palmitoylation of the UL51 protein through the N-terminal cysteine at position 9 was necessary for its Golgi localization. Protease digestion analysis suggested that the UL51 protein localized on the cytoplasmic face of the membrane in UL51-transfected cells, while in infected cells it localized mainly to the inside of cytoplasmic vesicles and/or the viral envelope. Transmission immunoelectron microscopy revealed an association of UL51 protein-specific labeling with cytoplasmic virions and also with some membranous structure. We infer from these observations that internalization of UL51 protein into the cytoplasmic vesicle and/or virion may occur in association with viral envelopment in HSV-infected cells.


title: TAP CBRN preparedness: knowledge, training and networks.

text: The main goal of this targeted agenda program (TAP) was the establishment of an international network that would be able to advise on how to improve education and training for chemical, biological, radiological, or nuclear (CBRN)) responders. By combining the members of the TAP group, the CBRN Task Force of the World Association for Disaster and Emergency Medicine (WADEM) and the European network of the Hesculaep Group, an enthusiastic and determined group has been established to achieve the defined goal. It was acknowledged that the bottlenecks for education and training for CBRN responders are mainly awareness and preparedness. For this reason, even basic education and training on CBRN is lacking. It was advised that the focus for the future should be on the development of internationally standardized protocols and standards. The face-to-face discussions of the TAP will be continued at future Hesculaep expert meetings. The intention is that during the 16WCDEM, the achievements of the established network will be presented.


Intrinsically contaminated alcohol-free mouthwash implicated in a nosocomial outbreak of Burkholderia cepacia colonization and infection.


title: Understanding the super-spreading events of SARS in Singapore.

text: INTRODUCTION It has been noted that SARS transmission is characterised by a few super-spreading events (SSEs) giving rise to a disproportionate number of secondary cases. Clinical and environmental features surrounding the index cases involved were compared with cases in non- SSEs. MATERIALS AND METHODS Data on 231 cases of probable SARS admitted to Tan Tock Seng Hospital (TTSH) were used. Index cases directly causing 10 or more secondary cases were classified as having been involved in SSEs; all others were defined as non-SSEs. RESULTS Only 5 cases were involved in SSEs; all 5 were isolated on day 5 of illness or later, and spent at least a brief period in a non-isolation ward; in contrast, amongst the 226 non-SSE cases, only 40.7% and 4.0% were isolated late and admitted to non-isolation wards respectively, and only 3.1% had both these environmental features present; the differences were highly significant (P = 0.012, P <0.001 and P <0.001 by Fisher's Exact test). When compared to 7 non-SSE cases with delayed isolation and an admission to non-isolation wards, SSEs were more likely to have co-morbid disease or require ICU care at time of isolation (P = 0.045 for both factors). CONCLUSION SSEs were likely due to a conglomeration of environmental factors of delayed isolation and admission to a non-isolation ward, coupled with severe disease stage at time of isolation.


title: Combination of functionalized nanoparticles and polymerase chain reaction-based method for SARS-CoV gene detection.

text: Rapid and sensitive detection of SARS associated coronavirus is critical for early diagnosis and control of severe acute respiratory syndrome. This study describes a method for the detection of SARS associated coronavirus gene by the combination of functionalized nanoparticles and PCR-based assay. In this method, the target cDNA of SARS associated coronavirus was firstly captured and enriched from the mixture of target cDNA and non-target cDNA by the use of the functionalized silica coated superparamagnetic nanoparticles. Additionally, the enriched target cDNA were amplified through a general symmetry PCR and then was selectively isolated from the double strands PCR products by applying the silica coated superparamagnetic nanoparticles again. Finally, we detected the amplified target cDNA by employing the functionalized silica coated fluorescent nanoparticles as signaling probes with a sandwich hybridization format. The results show that the target cDNA can be assayed successfully with a detection limit of 2.0 x 10(3) copies and the nonspecific amplification could be inhibited. In addition, the detection procedure is rapid and can be completed in less than 6 h. Our results suggest that this approach will provide promising prospects for other pathogens detection.


Monoclonal antibodies to two bovine coronavirus glycoproteins neutralize virus infectivity.


title: Cleavage between replicase proteins p28 and p65 of mouse hepatitis virus is not required for virus replication.

text: The p28 and p65 proteins of mouse hepatitis virus (MHV) are the most amino-terminal protein domains of the replicase polyprotein. Cleavage between p28 and p65 has been shown to occur in vitro at cleavage site 1 (CS1), (247)Gly downward arrow Val(248), in the polyprotein. Although critical residues for CS1 cleavage have been mapped in vitro, the requirements for cleavage have not been studied in infected cells. To define the determinants of CS1 cleavage and the role of processing at this site during MHV replication, mutations and deletions were engineered in the replicase polyprotein at CS1. Mutations predicted to allow cleavage at CS1 yielded viable virus that grew to wild-type MHV titers and showed normal expression and processing of p28 and p65. Mutant viruses containing predicted noncleaving mutations or a CS1 deletion were also viable but demonstrated delayed growth kinetics, reduced peak titers, decreased RNA synthesis, and small plaques compared to wild-type controls. No p28 or p65 was detected in cells infected with predicted noncleaving CS1 mutants or the CS1 deletion mutant; however, a new protein of 93 kDa was detected. All introduced mutations and the deletion were retained during repeated virus passages in culture, and no phenotypic reversion was observed. The results of this study demonstrate that cleavage between p28 and p65 at CS1 is not required for MHV replication. However, proteolytic separation of p28 from p65 is necessary for optimal RNA synthesis and virus growth, suggesting important roles for these proteins in the formation or function of viral replication complexes.


title: The role of the intensive care unit environment in the pathogenesis and prevention of ventilator-associated pneumonia.

text: Ventilator-associated pneumonia is preceded by lower-respiratory-tract colonization by pathogenic microorganisms that derive from endogenous or exogenous sources. Most ventilator-associated pneumonias are the result of exogenous nosocomial colonization, especially, pneumonias caused by resistant bacteria, such as methicillin-resistant Staphylococcus aureus and multi-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, or by Legionella species or filamentous fungi, such as Aspergillus. Exogenous colonization originates from a very wide variety of animate and inanimate sources in the intensive care unit environment. As a result, a strategic approach that combines measures to prevent cross-colonization with those that focus on oral hygiene and prevention of microaspiration of colonized oropharyngeal secretions should bring the greatest reduction in the risk of ventilator-associated pneumonia. This review examines strategies to prevent transmission of environmental pathogens to the vulnerable mechanically-ventilated patient.


title: Synergism of the 3'-untranslated region and an internal ribosome entry site differentially enhances the translation of a plant virus coat protein.

text: The use of internal ribosome entry sites (IRESs) is one of the unorthodox mechanisms exploited by viruses to initiate the translation of internal genes. Herein, we report a plant virus exploiting an IRES and its 3'-untranslated region (UTR) to express its internal genes, notably the 3'-proximal viral coat protein gene. Hibiscus chlorotic ringspot virus (HCRSV), a positive-strand non-polyadenylated RNA virus, was demonstrated to harbor a unique 100-nucleotide (nt) IRES, located 124 nt upstream of the coat protein gene, that could function in wheat germ extract, rabbit reticulocyte lysate, and mammalian cells. In comparison with other known IRESs of picornaviruses and eukaryotic mRNAs, this 100-nt IRES is distinctively short and simple. The IRES activity was tested in homologous and heterologous bicistronic constructs, and the expression of the 3'-proximal gene was enhanced when the 3'-UTR was present. When the IRES element was bisected, each half still possessed IRES activity and could initiate internal translation on its own. Site-directed mutagenesis and deletion analyses revealed that the primary sequence within the 5' half was crucial for IRES activity, whereas the primary sequence of the second half and a GNRA motif were non-essential. To our knowledge, this is the first report describing a mechanism whereby an IRES, located in the 3' portion of the virus genome, co-operates with the 3'-UTR to enhance gene expression differentially.


title: Coronavirus-like particles in Aboriginals and non-Aboriginals in Western Australia.

text: Pleomorphic virus-like particles which resemble coronaviruses in morphology were found in faecal specimens from Aboriginal and non-Aboriginal children in Western Australia. They were equally prevalent in those with or without symptoms of diarrhoea. A much greater proportion of Aboriginal than non-Aboriginal children were found to be excreting the particles. The proportion of children who excreted the virus-like particles increased with age. Coronavirus-like particles, indistinguishable from those found in humans, were found in a number of Aboriginals' dogs.


title: Control of Extensively Drug-Resistant Tuberculosis (XDR-TB): A Root Cause Analysis.

text: The threat of global infectious agents has the potential to cripple national and global economies, as the outbreaks of SARS, Avian Flu, H1N1, and XDR-TB have demonstrated. This article offers a Root Cause Analysis (RCA) of one public health case study - the Speaker case of XDR-TB - pinpointing the underlying causal relationships associated with this global health incident and proposing recommendations for preventing its recurrence. An RCA approach identifies corrective actions directed at the root causes of the problem and advances them as necessary to eliminate global contagion with its major international public health risks. To my knowledge, this is the first root cause analysis of a global health problem. The reform this article proposes would be to add a standardized procedure akin to the informed consent process in clinical ethics, but within a shared health governance framework. This approach, addressing infectious agents at their origins or source, is potentially a more effective strategy to reduce uncertainty and avert global health threats.


title: [A clinicopathological study on 3 cases of severe acute respiratory syndrome].

text: OBJECTIVE To study the pathological characteristics of severe acute respiratory syndrome (SARS) and its relationship to clinical manifestation. METHODS Tissue specimens from 3 autopsy cases of diagnosed SARS were studied under microscopy and the clinical data were reviewed. RESULTS The typical pathological changes of lungs were diffuse hemorrhage on surface. A mixture features of serous, fibrinous and hemorrhagic inflammation were seen in most pulmonary alveoli with engorgement of capillary and there were microthrombosis in some capillary. Pulmonary alveoli became thick with interstitial mononuclear inflammatory infiltration, diffused alveoli damage, desquamation of pneumocytes and hyaline-membrane formation. Fibrinoid materials and erythrocytes could be found in alveolar spaces. There were thrombo-embolisms in some bronchial artery. Meanwhile, haemorrhagic necrosis was showed in lymph nodes and spleen with attenuation of lymphocytes. Other atypical pathological changes, such as hydropic degeneration, fatty degeneration, interstitial cell proliferation and some lesions observed in liver, heart, kidney, pancreas may have existed before the hospitalization. CONCLUSION Severe damages of pulmonary and immunological system damage are responsible for clinical features of SARS and may lead to death of patients.


title: Functional differences in the peplomer glycoproteins of feline coronavirus isolates.

text: The feline coronaviruses can be divided into two distinct antigenic groups on the basis of antigenic differences found on the peplomer (E2) glycoprotein of the virus. Because the E2 glycoprotein is responsible for many of the biological functions of coronaviruses, experiments were done to determine whether there were any E2 functional differences between these two antigenic groups. The avirulent feline infectious peritonitis virus (FIPV) isolate FIPV-UCD-2, which has one antigenic type of E2, was less rapidly internalized and could not spread from cell to cell in the presence of neutralizing antibody. Two virulent isolates, FIPV-DF2 and FIPV-79-1146, as well as the non-FIP-causing feline enteric coronavirus (FECV) isolate FECV-79-1683, all of which have the second antigenic type of E2, were very rapidly internalized and were able to spread from cell to cell despite the presence of neutralizing antibody. The avirulent FIPV-UCD-2 and FECV-79-1683 isolates were more labile at 37 degrees C at pHs of 6.5 and above than were the virulent FIPV-DF2 and FIPV-79-1146 isolates.


title: [Covid-19 in patients on dialysis: infection prevention and control strategies].

text: Covid-19 is a disease caused by a new coronavirus presenting a variability of flu-like symptoms including fever, cough, myalgia and fatigue; in severe cases, patients develop pneumonia, acute respiratory distress syndrome, sepsis and septic shock, that can result in their death. This infection, which was declared a global epidemic by the World Health Organization, is particularly dangerous for dialysis patients, as they are frail and more vulnerable to infections due to the overlap of multiple pathologies. In patients with full-blown symptoms, there is a renal impairment of various degrees in 100% of the subjects observed. However, as Covid-19 is an emerging disease, more work is needed to improve prevention, diagnosis and treatment strategies. It is essential to avoid nosocomial spread; in order to control and reduce the rate of infections it is necessary to strengthen the management of medical and nursing personnel through the early diagnosis, isolation and treatment of patients undergoing dialysis treatment. We cover here a series of recommendations for the treatment of dialysis patients who are negative to the virus, and of those who are suspected or confirmed positive.


title: Porcine reproductive and respiratory syndrome virus-infected alveolar macrophages contain no detectable levels of viral proteins in their plasma membrane and are protected against antibody-dependent, complement-mediated cell lysis.

text: Porcine reproductive and respiratory syndrome virus (PRRSV) can evade the host immune system, which results in prolonged virus replication for several weeks to several months. To date, the mechanisms of PRRSV immune evasion have not been investigated in detail. One possible immune-evasion strategy is to avoid incorporation of viral proteins into the plasma membrane of infected cells, as this prevents recognition by virus-specific antibodies and consequent cell lysis either by the classical complement pathway or by antibody-dependent, cell-mediated cytotoxicity. In this study, viral proteins were not observed in the plasma membrane of in vitro-infected macrophages by using confocal microscopy or flow cytometry. Subsequently, the sensitivity of PRRSV-infected macrophages towards antibody-dependent, complement-mediated cell lysis (ADCML) was determined by using an ADCML assay. A non-significant percentage of PRRSV-infected cells were killed in the assay, showing that in vitro PRRSV-infected macrophages are protected against ADCML. PRRSV proteins were not detected in the plasma membrane of in vivo-infected alveolar macrophages and ADCML was also not observed. Together, these data indicate that viral proteins are not incorporated into the plasma membrane of PRRSV-infected macrophages, which makes infected cells invisible to PRRSV-specific antibodies. This absence of viral proteins on the cell surface could explain the protection against ADCML observed for in vitro and in vivo PRRSV-infected macrophages, and may play a role in virus persistence.


title: CrFK feline kidney cells produce an RD114-like endogenous virus that can package murine leukemia virus-based vectors.

text: The feline kidney cell line CrFK is used extensively for viral infectivity assays and for study of the biology of various retroviruses and derived vectors. We demonstrate the production of an endogenous, RD114-like, infectious retrovirus from CrFK cells. This virus also is shown to efficiently package Moloney murine leukemia virus vectors.


title: Mutational analysis of the active centre of coronavirus 3C-like proteases.

text: Formation of the coronavirus replication-transcription complex involves the synthesis of large polyprotein precursors that are extensively processed by virus-encoded cysteine proteases. In this study, the coding sequence of the feline infectious peritonitis virus (FIPV) main protease, 3CL(pro), was determined. Comparative sequence analyses revealed that FIPV 3CL(pro) and other coronavirus main proteases are related most closely to the 3C-like proteases of potyviruses. The predicted active centre of the coronavirus enzymes has accepted unique replacements that were probed by extensive mutational analysis. The wild-type FIPV 3CL(pro) domain and 25 mutants were expressed in Escherichia coli and tested for proteolytic activity in a peptide-based assay. The data strongly suggest that, first, the FIPV 3CL(pro) catalytic system employs His(41) and Cys(144) as the principal catalytic residues. Second, the amino acids Tyr(160) and His(162), which are part of the conserved sequence signature Tyr(160)-Met(161)-His(162) and are believed to be involved in substrate recognition, were found to be indispensable for proteolytic activity. Third, replacements of Gly(83) and Asn(64), which were candidates to occupy the position spatially equivalent to that of the catalytic Asp residue of chymotrypsin-like proteases, resulted in proteolytically active proteins. Surprisingly, some of the Asn(64) mutants even exhibited strongly increased activities. Similar results were obtained for human coronavirus (HCoV) 3CL(pro) mutants in which the equivalent Asn residue (HCoV 3CL(pro) Asn(64)) was substituted. These data lead us to conclude that both the catalytic systems and substrate-binding pockets of coronavirus main proteases differ from those of other RNA virus 3C and 3C-like proteases.


Imaging Findings in Four COVID-19 Patients.


title: Needle-free vaccine delivery.

text: The need for minimally invasive delivery methods is urgent. As the number of registered vaccines increases, so does the number of injections. The use of sharps can be unsafe and needle immunisation is less suitable for mass immunisations during emergencies such as pandemics or bioterrorist attacks. The approach of combining vaccines has limitations due to high development costs, risk of pharmaceutical or immunological interference and economic risks. Advancements in the development of alternatives to injection with syringes and needles are discussed in this paper, and include: mucosal vaccination, injection without needles and vaccine delivery via the skin.


title: The common cold, pattern sensitivity and contrast sensitivity.

text: Results from two studies involving challenge with respiratory syncytial viruses showed that volunteers who developed colds were more sensitive to a visually distracting pattern presented prior to virus challenge than were volunteers who did not get a cold. Volunteers with sub-clinical infections reported more illusions after virus challenge than they had done before, whereas uninfected volunteers and those with colds tended to report fewer illusions on the second test. These effects did not occur when volunteers were challenged with either a coronavirus or rhinovirus. Overall, the results confirm that behavioural measures may be related to susceptibility to subsequent illness, and that viral infections may influence visual perception. They also show that the effects vary according to the nature of the infecting agent, which agrees with results from studies looking at other aspects of behaviour.


title: Inner structures of some coronaviruses.

text: When treated with formaldehyde, Tween 80, sodium oleate and Nonidet P-40, avian infectious bronchitis virus, porcine transmissible gastroenteritis virus, neonatal calf diarrhea coronavirus, porcine hemagglutinating encephalomyelitis virus as well as the human coronavirus show similar inner structures by negative staining. The first one is an inner membranous bag. This structure could be evaginated following treatments used and does not show the characteristic projections of coronaviruses. Subsequently, the inner fold could be separated from the outer membrane at the point of junction between these two membranes. Each virus does not react in the same way to the action of the different products. The transmissible gastroenteritis virus appears more sensitive to treatments than other viruses. On the other hand, the hemagglutinating encephalomyelitis virus is the most resistant. The variable sensitivities of these viruses are not related to the type of host-cells. Also, a second internal structure, which is more dense than the viral particle, encircles partially the aperture of the internal tongue-shaped structure and seems to emerge from the viral particle through the aperture of the inner bag.


title: [Optimal stroke prevention in the geriatric patient with atrial fibrillation: position paper of an interdisciplinary expert panel].

text: BACKGROUND The optimal approach to stroke prevention in geriatric patients with atrial fibrillation (AF) has not been adequately clarified. Despite their high risk of stroke and clear indication for anticoagulation according to established risk scores, in practice geriatric AF patients often are withheld treatment because of comorbidities and comedications, concerns about low treatment adherence or fear of bleeding events, in particular due to falls. METHOD The present position paper summarises the outcomes of an expert panel discussion held by hospital-based and office-based physicians with ample experience in the treatment of geriatric patients. RESULTS AND CONCLUSIONS The panel agreed that geriatric patients should receive oral anticoagulation as a rule, unless a comprehensive neurological and geriatric assessment (including clinical examination, gait tests and validated instruments such as Modified Rankin Scale, Mini-mental state examination or Timed Test of Money Counting) provides sound reasons for refraining from treatment AII patients with a history of falls should be thoroughly evaluated for further evaluation of the causes. Patients with CHADS2 score ≥ 2 should receive anticoagulation even if at high risk for falls. The novel oral anticoagulants (NOAC) facilitate management in the geriatric population with AF (no INR monitoring needed, easier bridging during interventions) and have an improved benefit-risk ratio compared to vitamin K antagonists. Drugs with predominantly non-renal elimination are safer in geriatric


title: [Detection of SARS-CoV RNA in stool samples of SARS patients by nest RT-PCR and its clinical value].

text: OBJECTIVE To investigate of severe acute respiratory syndrome (SARS) convalescent stool shedding by RT-PCR. METHODS One hundred and three stool samples from 46 SARS patients were collected on May 16th, 20th, and 23rd, 2003. For each sample, RNA was extracted using commercial kit and 7 Nest RT-PCR using a 14-pair different SARS-associated coronavirus (SARS-CoV) special primers were carried out simultaneously. RESULTS Among these 46 SARS patients, 17 cases (37.0%) were stool SARS-CoV RT-PCR negative, and 29 cases (63.0%) were SARS-CoV RT-PCR positive. The duration of positive cases lasted (31.76 +/- 10.78) d (12-64 d). The longest stool shedding case in this study lasted 64 days. Two serial stool samples and for each sample 2 RT-PCR tests using different primers were positive in this case. CONCLUSIONS Our study observed longest stool shedding of SARS patients to be 64 days after initial onset of SARS. The average stool shedding was 32 days. Hence it is important to think highly of SARS convalescent patient stool sterilization.


title: Characterization of the RNA components of a putative molecular switch in the 3' untranslated region of the murine coronavirus genome.

text: RNA virus genomes contain cis-acting sequence and structural elements that participate in viral replication. We previously identified a bulged stem-loop secondary structure at the upstream end of the 3' untranslated region (3' UTR) of the genome of the coronavirus mouse hepatitis virus (MHV). This element, beginning immediately downstream of the nucleocapsid gene stop codon, was shown to be essential for virus replication. Other investigators discovered an adjacent downstream pseudoknot in the 3' UTR of the closely related bovine coronavirus (BCoV). This pseudoknot was also shown to be essential for replication, and it has a conserved counterpart in every group 1 and group 2 coronavirus. In MHV and BCoV, the bulged stem-loop and pseudoknot are, in part, mutually exclusive, because of the overlap of the last segment of the stem-loop and stem 1 of the pseudoknot. This led us to hypothesize that they form a molecular switch, possibly regulating a transition occurring during viral RNA synthesis. We have now performed an extensive genetic analysis of the two components of this proposed switch. Our results define essential and nonessential components of these structures and establish the limits to which essential parts of each element can be destabilized prior to loss of function. Most notably, we have confirmed the interrelationship of the two putative switch elements. Additionally, we have identified a pseudoknot loop insertion mutation that appears to point to a genetic interaction between the pseudoknot and a distant region of the genome.


title: Diagnosis of acute non-bacterial gastroenteritis by rotavirus detection and serology.

text: In 127 infants and young children suffering from acute non-bacterial gastroenteritis, diagnosis of rotavirus infection was done by virus detection and serology. Human rotavirus (HRV) detection was performed by direct electron microscopy (EM), conventional immune electron microscopy (IEM) and/or solid phase immune electron microscopy ( SPIEM ); rotavirus antigens were detected by indirect double-antibody sandwich (DAS) ELISA and HRV isolation was attempted in MA-104 or LLC-MK2 cell cultures. HRV serology was done on paired sera from all the patients by the indirect immunoperoxidase antibody (IPA) technique for HRV IgG determination, and by an indirect ELISA method using a purified HRV Wa strain as a solid phase. HRV particles were detected by EM and/or IEM in 53 cases (41.7%) and by SPIEM in 5 additional cases; HRV antigens were demonstrated by indirect DAS ELISA in the same 53 cases, whereas 40 cases (31.4%) were positive for HRV isolation in cell cultures. Sixty-four patients (50.3%) seroconverted by IPA and ELISA, including all the cases (58) positive for rotavirus detection in stools and 6 additional cases. Thus, SPIEM appears to be the most sensitive technique for detecting a few virus particles in stool specimens, but HRV serology is the most sensitive method for diagnosing HRV infections retrospectively, when paired sera are drawn at an appropriate time. However, EM possess the great advantage of detecting in fecal specimens viral agents other than rotaviruses, such as adenoviruses, enteric coronaviruses, small round viruses, astroviruses and others.


Pursuing excellence in neurosurgical innovation.


A serologic investigation for coronavirus and Breda virus antibody in winter dysentery of dairy cattle in the northeastern United States.


title: Listeric meningoencephalomyelitis in a cougar (Felis concolor): characterization by histopathologic, immunohistochemical, and molecular methods.

text: Listeria monocytogenes has been recognized as an important food-borne pathogen in animals. Records of the disease caused by this bacterium in large felids are, however, rare. The nervous form of listeriosis was diagnosed in a 12-year-old male cougar (Felis concolor) with a several-day history of neurologic disease characterized by excess salivation, head pressing, and circling that progressed to recumbency and death. Microscopically, the main alteration in the brain and spinal cord was a variably severe meningoencephalomyelitis composed mainly of mononuclear cell aggregates with fewer neutrophils. L. monocytogenes was isolated from the brain by microbiological culture, and L. monocytogenes antigen was detected in formalin-fixed, paraffin-embedded sections of brain and spinal cord by immunohistochemical analysis. On the basis of the nucleotide sequence of the 16S rRNA gene, the isolated strain was determined to be serotype 1/2a. Food-borne transmission of the bacterium was suspected, but food was not available for testing.


title: Essential veterinary education in the cultural, political and biological complexities of international trade in animals and animal products.

text: Globalisation has changed the veterinary profession in many ways and academic institutes may need to re-tool to help future professionals deal with the changes in a successful and productive way. The remarkably expanded and expanding volume of trade and traffic in animals and animal products means that to be effective veterinarians must grasp some of the complexities inherent in this trade. Being able to engage productively in cross-cultural dialogue will be important in negotiations over livestock shipments and also within the context of the delivery of medical services to companion animals in societies that are becoming increasingly diverse. Understanding the political landscapes that influence trade decisions will help to expedite agreements and facilitate the transfer of goods and materials that involve animal health. Disease emergence will continue to occur, and an awareness of the factors responsible and the response measures to undertake will help to contain any damage.


title: Alpha2,6-linked sialic acid acts as a receptor for Feline calicivirus.

text: Feline calicivirus (FCV) is a major causative agent of respiratory disease in cats. It is also one of the few cultivatable members of the family Caliciviridae. It has recently been reported that FCV binding is in part due to interaction with junction adhesion molecule-A. This report describes the characterization of additional receptor components for FCV. Chemical treatment of cells with sodium periodate showed that FCV recognized carbohydrate moieties on the surface of permissive cells. Enzymic treatment with Vibrio cholerae neuraminidase demonstrated that sialic acid was a major determinant of virus binding. Further characterization using linkage-specific lectins from Maackia amurensis and Sambucus nigra revealed that FCV recognized sialic acid with an alpha2,6 linkage. Using various proteases and metabolic inhibitors, it was shown that alpha2,6-linked sialic acid recognized by FCV is present on an N-linked glycoprotein.


title: Molecular characterization of the 229E strain of human coronavirus.

text: Human coronaviruses (HCV) cause various respiratory, gastrointestinal and possibly neurological disorders. Very little is known of the molecular biology of these ubiquitous pathogens. We have undertaken the molecular characterization of the prototype 229E strain of HCV. The virus grew to the highest titers on a human embryonic lung cell line (L132) at 33 degrees C and purification was optimal on Renografin-60 gradients. Metabolic labeling with [35S]methionine or [3H]glucosamine or galactose and analysis by SDS-PAGE revealed at least five structural proteins, which could be identified by analogy with murine coronaviruses as follows: the spike glycoprotein (E2/S), in both monomeric (88-97 kDa) and dimeric (190-200) forms, the nucleoprotein (N) at 52-53 kDa and the matrix protein (E1/M), in both glycosylated (25-26 kDa) and non-glycosylated (20-22 kDa) forms. Monomeric, dimeric and multimeric (greater than 200 kDa) forms of E2/S incorporated glucosamine and galactose, whereas only galactose was incorporated into E1/M. Multimers of E1/M, with apparent molecular masses of 44, 74 and 140 kDa, were formed in the absence of a reducing agent.


Mechanical Small Bowel Obstruction Caused by a Retained Free Intraperitoneal Staple Following Laparoscopic Appendectomy.


title: Modelling the transmission of airborne infections in enclosed spaces.

text: The Wells-Riley equation for modelling airborne infection in indoor environments is incorporated into an SEIR epidemic model with a short incubation period to simulate the transmission dynamics of airborne infectious diseases in ventilated rooms. The model enables the effect of environmental factors such as the ventilation rate and the room occupancy to be examined, and allows the long-term impact of infection control measures to be assessed. A theoretical parametric study is carried out to demonstrate how changes to both the physical environment and infection control procedures may potentially limit the spread of short-incubation-period airborne infections in indoor environments such as hospitals.


title: Characterization of replicative intermediate RNA of mouse hepatitis virus: presence of leader RNA sequences on nascent chains.

text: Mouse hepatitis virus A59 codes for seven mRNAs in infected cells. These mRNAs are transcribed from a minus (-) strand template of genome length and contain a leader RNA at their 5' ends. To further elucidate the mechanism of coronavirus transcription, we examined the structure of mouse hepatitis virus replicative intermediates (RIs) isolated by 2 M NaCl precipitation and Sepharose 2-B column chromatography. Purified RIs migrated as a single species on agarose gels and sedimented between 12 and 38S on 10 to 25% sucrose gradients. The complexes were readily heat denatured into a heterogeneous population of smaller RNA molecules which probably represent nascent plus (+) strands. RNase A digestion of RIs produced a single replicative form which sedimented between 30 and 32S. These data suggest that the RI is composed of a single genome-sized (-) strand hydrogen bonded to an average of 4 to 6.5 nascent (+) strands. In contrast, a column-purified replicative form was extremely resistant to RNase A digestion and heat denaturation and migrated as a single RNA species on agarose gels and sucrose gradients. Oligonucleotide fingerprinting of an RI revealed the presence of the 5' leader RNA on the nascent (+) strands. In addition, an average of 6.2 cap structures were present in each RI, which agrees with the average number of nascent (+) strands per RI. These data suggest that the leader RNA is utilized as a primer for mouse hepatitis virus RNA transcription and is not added to mRNA post-transcriptionally.


title: Viral ecology and the maintenance of novel host use.

text: Viruses can occasionally emerge by infecting new host species. However, the early phases of emergence can hinge upon ecological sustainability of the virus population, which is a product of both within-host population growth and between-host transmission. Insufficient growth or transmission can force virus extinction before the latter phases of emergence, where genetic adaptations that improve host use may occur. We examined the early phase of emergence by studying the population dynamics of RNA phages in replicated laboratory environments containing native and novel host bacteria. To predict the breadth of transmission rates allowing viral persistence on each species, we developed a simple model based on in vitro data for phage growth rate over a range of initial population densities on both hosts. Validation of these predictions using serial passage experiments revealed a range of transmission rates for which the native host was a source and the novel host was a sink. In this critical range of transmission rates, periodic exposure to the native host was sufficient for the maintenance of the viral population on the novel host. We argue that this effect should facilitate adaptation by the virus to utilize the novel host--often crucial in subsequent phases of emergence.


title: Pilot study comparing total intravenous anesthesia to inhalational anesthesia in endoscopic sinus surgery: novel approach of blood flow quantification.

text: OBJECTIVES We compared anesthesia with sevoflurane-remifentanil hydrochloride (SR) to total intravenous anesthesia with propofol-remifentanil hydrochloride (PR) in patients undergoing endoscopic sinus surgery for chronic rhinosinusitis in terms of sinonasal mucosal blood flow, the surgical field visualization score, and blood loss. METHODS We performed a double-blinded prospective study at a tertiary care center in 23 adults scheduled to undergo endoscopic sinus surgery for chronic rhinosinusitis. The patients were randomized to receive SR or PR. The sinonasal mucosal blood flow was measured by optical rhinometry. The surgical field visualization score was based on the Boezaart scale. RESULTS The groups had similar clinical characteristics. During the 60- to 90-minute and 90- to 120-minute operative time windows, the blood flow was significantly greater in the PR group than in the SR group (p = 0.04 and p = 0.03, respectively). The amounts of blood loss in the PR and SR groups were 152.9 +/- 161.3 mL and 355.9 +/- 393.4 mL, respectively (p = 0.12). The median ratios of the surgical field visualization score to the number of sinuses operated on in the PR and SR groups were 2.1 and 1.8, respectively (p = 0.52). CONCLUSIONS The intraoperative blood flow, as determined by optical rhinometry, was significantly greater with anesthesia with PR than with anesthesia with SR, 1 hour into the procedure; however, this difference did not translate into differences in the amounts of operative blood loss or in the surgical field visualization scores.


title: In vivo titration of white spot syndrome virus (WSSV) in specific pathogen-free Litopenaeus vannamei by intramuscular and oral routes.

text: White spot syndrome virus (WSSV) is a devastating pathogen in shrimp aquaculture. Standardized challenge procedures using a known amount of infectious virus would assist in evaluating strategies to reduce its impact. In this study, the shrimp infectious dose 50% endpoint (SID50 ml(-1)) of a Thai isolate of WSSV was determined by intramuscular inoculation (i.m.) in 60 and 135 d old specific pathogen-free (SPF) Litopenaeus vannamei using indirect immunofluorescence (IIF) and 1-step polymerase chain reaction (PCR). Also, the lethal dose 50% endpoint (LD50 ml(-1)) was determined from the proportion of dead shrimp. The median virus infection titers in 60 and 135 d old juveniles were 10(6.8) and 10(6.5) SID50 ml(-1), respectively. These titers were not significantly different (p > or = 0.05). The titration of the WSSV stock by oral intubation in 80 d old juveniles resulted in approximately 10-fold reduction in virus titer compared to i.m. inoculation. This lower titer is probably the result of physical and chemical barriers in the digestive tract of shrimp that hinder WSSV infectivity. The titers determined by infection were identical to the titers determined by mortality in all experiments using both i.m. and oral routes at 120 h post inoculation (hpi), indicating that every infected shrimp died. The determination of WSSV titers for dilutions administered by i.m. and oral routes constitutes the first step towards the standardization of challenge procedures to evaluate strategies to reduce WSSV infection.


title: Fever, pulmonary haemorrhage, and acute renal failure in a young girl.

text: Leptospirosis is rarely reported in children. It is easily treated with antibiotics but can be fatal if treatment is delayed. A 12-year-old girl was diagnosed with Weil syndrome, a severe form of leptospirosis, 10 days after returning from Mainland China. She presented with fever, hypotension, jaundice, and acute renal failure. She had used well water for bathing and swum in freshwater.


title: C-type lectins L-SIGN and DC-SIGN capture and transmit infectious hepatitis C virus pseudotype particles.

text: The molecular mechanisms involved in the hepatic tropism of hepatitis C virus (HCV) have not been identified. We have shown previously that liver-expressed C-type lectins L-SIGN and DC-SIGN bind the HCV E2 glycoprotein with high affinity (Lozach, P. Y., Lortat-Jacob, H., de Lacroix de Lavalette, A., Staropoli, I., Foung, S., Amara, A., Houles, C., Fieschi, F., Schwartz, O., Virelizier, J. L., Arenzana-Seisdedos, F., and Altmeyer, R. (2003) J. Biol. Chem. 278, 20358-20366). To analyze the functional relevance of this interaction, we generated pseudotyped lentivirus particles presenting HCV glycoproteins E1 and E2 at the virion surface (HCV-pp). High mannose N-glycans are present on E1 and, to a lesser extent, on E2 proteins of mature infectious HCV-pp. Such particles bind to both L-SIGN and DC-SIGN, but they cannot use these receptors for entry into cells. However, infectious virus is transmitted efficiently when permissive Huh-7 cells are cocultured with HCV-pp bound to L-SIGN or to DC-SIGN-positive cell lines. HCV-pp transmission via L-SIGN or DC-SIGN is inhibited by characteristic inhibitors such as the calcium chelator EGTA and monoclonal antibodies directed against lectin carbohydrate recognition domains of both lectins. In support of the biological relevance of this phenomenon, dendritic cells expressing endogenous DC-SIGN transmitted HCV-pp with high efficiency in a DC-SIGN-dependent manner. Our results support the hypothesis that C-type lectins such as the liver sinusoidal endothelial cell-expressed L-SIGN could act as a capture receptor for HCV in the liver and transmit infectious virions to neighboring hepatocytes.


docid: lgweymvm

title: Lysosomal sorting mutants of coronavirus E1 protein, a Golgi membrane protein.

text: As a model for the intracellular sorting of Golgi membrane proteins, we are studying the E1 protein of the coronavirus Mouse Hepatitis Virus A59. The wild-type protein, when expressed from synthetic RNA, is localised in the Golgi complex. When the second and third of the three predicted membrane-spanning sequences were deleted from the protein, the resulting mutant was retained in the endoplasmic reticulum. In contrast, removal of the first and second membrane-spanning sequences allowed the protein to pass through the Golgi complex and reach the lysosomes. Likewise, when 40 amino acids were deleted from the C-terminal cytoplasmic part of E1, the truncated protein was transported to the lysosomes. We discuss the implications of these results for the structure of the E1 protein and the mechanism by which it is localised in the cell.


title: Differences in the susceptibility of some penaeid prawn species to gill-associated virus (GAV) infection.

text: Four species of penaeid prawn cultured in Australia (Penaeus monodon, Penaeus esculentus, Marsupenaeus japonicus and Fenneropenaeus merguiensis) were injected with a virulent preparation of gill-associated virus (GAV). P. monodon (average weight = 8.9, 13.9 and 19.2 g), P. esculentus (average weight = 19.5 g), F. merguiensis (average weight = 10.5 g), and small (average weight = 5.8 g) M. japonicus displayed overt signs of disease and mortalities which reached 82 to 100% within 23 d post-injection. Cumulative mortalities in P. esculentus and F. merguiensis were significantly lower than for P. monodon of the same size class. Medium (average weight = 13.0 g) M. japonicus also developed overt signs of disease but cumulative mortalities were not significantly higher than uninfected controls. Large (average weight = 20.3 g) M. japoncius did not display symptoms of disease and there were no significant mortalities up to 23 d post-injection.


title: Singapore's experience of SARS.

text: The coronavirus that causes severe acute respiratory syndrome (SARS) is transmitted mainly via respiratory droplets. Typical presenting symptoms are akin to those of ordinary pneumonia. Young patients start with fever, chills, malaise, headache, or myalgia; cough and dyspnoea follow. Older persons and those taking corticosteroids may have neither fever nor respiratory symptoms. Exceptional suspicion is needed to identify SARS early in the illness. During an outbreak, even patients with low suspicion of SARS should be promptly isolated, and all contacts quarantined. Health workers need training in the use of appropriate barriers against droplets and other body fluids. Any fever cluster in patients or carers requires immediate action: discharges, visits, and transfers between wards and hospitals should be stopped. Halting hospital admissions and ten-day quarantine of suspected cases create wide buffer zones. To counter a possible resurgence of SARS, a system of prepared isolation and quarantine facilities is important.


title: Duration of immunity in red wolves (Canis rufus) following vaccination with a modified live parvovirus and canine distemper vaccine.

text: There is growing information available regarding duration of immunity for core vaccines in both domestic and nondomestic species. Vaccination protocols in nondomestic canids have frequently followed guidelines developed for the domestic dog; however, these protocols can be inappropriate for nondomestic canids such as the African wild dog (Lycaon pictus), leaving some animals susceptible to infectious disease and others at risk for contracting vaccine-induced disease. In this study, red wolves (Canis rufus) were vaccinated against canine distemper virus (CDV) and canine parvovirus (CPV) and vaccination titers were followed annually for 3 yr. One hundred percent of wolves developed and maintained a positive titer to CDV for 3 yr and 96.9% of wolves developed and maintained a positive titer to CPV for 3 yr. Seroconversion for canine adenovirus was sporadic. The results of this study support decreasing the frequency of vaccine administration in the red wolf population to a triennial basis.


title: On medical confidentiality (not only) in time of coronavirus.

text: One of the compulsory secret exceptions derives from the situation within which the data about patient must be provided to the third person in the interest of his/her health protection. Despite some interpretation difficulties any providing information according to this legal exception is allowed only on the base of proved and re-examined facts. The state of emergency itself is not the base for the compulsory secret breach.


title: Studies of SARS virus vaccines.

text: 1. Intranasal vaccination using inactivated SARS coronavirus (SARS-CoV) vaccine with adjuvant can induce strong systemic (serum immunoglobulin [Ig] G) and respiratory tract local (tracheal-lung wash fluid IgA) antibody responses with neutralising activity. 2. RBD-Fc (protein-based vaccine) is able to induce effective neutralising antibodies able to provide protection from SARS-CoV infection in animal models. 3. A single dose of RBD-rAAV vaccination can induce adequate neutralising antibody against SARS-CoV infection. 4. Additional doses of vaccine increased the production of neutralising antibody 5-fold compared with a single dose. 5. RBD-rAAV vaccination provoked a prolonged antibody response with continually increasing levels of neutralising activity. 6. Intranasal vaccination with RBD-rAAV induced local IgA and systemic IgG neutralising antibodies and specific T-cell responses, able to protect against SARS-CoV infection in animal models. 7. When compared with the RBD-rAAV prime/boost vaccination, RBD-rAAV prime/RBD-peptide boost induced similar levels of Th1 and neutralising antibody responses that protected vaccinated mice from subsequent SARS-CoV challenges,but stronger Th2 and CTL responses. 8. Overall, our findings suggest that the inactivated vaccine, RBD-Fc and RBD-rAAV, can be further developed into effective and safe vaccines against SARS and that intranasal vaccination may be the preferred route of administration.


title: Severe acute respiratory syndrome: thin-section computed tomography features, temporal changes, and clinicoradiologic correlation during the convalescent period.

text: OBJECTIVE To evaluate thin-section computed tomography findings of patients with severe acute respiratory syndrome (SARS) in the convalescent period and to correlate the results with clinical parameters and lung function tests. METHODS Ninety-nine severe acute respiratory syndrome patients with persistent changes on follow-up chest radiography were included. One hundred seventy computed tomography examinations at baseline (n=70), 3 months (n=56), and 6 months (n=44) were retrospectively evaluated to determine the extent of ground-glass opacification, reticulation, and total parenchymal involvement. Patients' demographic information, clinical information during treatment, and results of lung function tests at 3 and 6 months were correlated with computed tomography findings. RESULTS A significant serial improvement in the extent of overall ground-glass opacification, overall reticulation, and total parenchymal involvement was observed (P <0.01). Advanced age, previous intensive care unit admission, mechanical ventilation, alternative treatment, higher peak lactate dehydrogenase, and peak radiographic involvement during treatment showed a positive correlation with overall reticulation and total parenchymal involvement at 6 months. There was a significant negative correlation between overall reticulation and total parenchymal involvement with diffusion capacity adjusted for hemoglobin at 3 and 6 months (P <0.01). CONCLUSION Lung changes on thin-section computed tomography of severe acute respiratory syndrome patients improved with time during the convalescent period and showed a significant correlation with advanced age, parameters indicating severe illness, and diffusion capacity adjusted for hemoglobin on follow-up.


docid: brsjbxdb

title: Transanal endoscopic video-assisted (TEVA) resection of early rectal lesions using a SILS port A single center experience.

text: UNLABELLED represents a safe and complete technique to remove benign lesions of the rectum not treatable by endoscopy and malignant rectal lesions at early stage. It is a valid alternative to transanal endoscopic microsurgery (TEM), to conventional transanal surgery and to transabdominal resection. METHODS In our operating Unit we performed a resection of 8 voluminous adenoma in the rectal ampulla with SILSTM-Port. RESULTS The mean age of the patients was of 51.1 years, the mean BMI was 23. There were not intra or post-operative complications nor conversions to conventional transanal excision or major resective surgery. The postoperative course was normal. The average time of hospitalization was 3 days. CONCLUSIONS TEVA is easier to perform than TEM and does not require a long training and specific and expensive material as the TEM does. TEVA might go to replace completely TEM. KEY WORDS Rectal tumours, SILS, TEVA.


title: [Dynamics of T lymphocyte subsets in SARS patients].

text: OBJECTIVE To study dynamics of T lymphocyte subsets in severe acute respiratory syndrome (SARS). METHODS Sequential anti-coagulated blood samples were collected from 46 cases of SARS patients during the 1st week, the 2nd week, the 3rd-5th week and the 8th-12th week after the infection. T lymphocyte subsets including CD3+CD4+ cells, CD3+CD8+ cells, naive CD4+ cells (CD4+CD45RA+CD62L+) and activated CD8+ cells (CD8+CD38+) were detected by 3-color flow cytometry. Fifty-six normal healthy blood donors were also detected as normal controls. RESULTS Compared with the results of normal controls, both of the percentages of CD4+ cells and CD8+ cells of SARS patients were in normal levels during the 1st week, but the cell counts decreased significantly to (306 +/- 140)/mm3 and (270 +/- 143)/mm3, respectively. The cell count of naive CD4+ subset also remarkably decreased to (96 +/- 49)/mm3, and the percentage of CD8+CD38+ subset was higher than that of normal controls [(59.3 +/- 12.6)% vs (44.9 +/- 12.5)%]. During the 3rd-5th week, the CD8+ cell count and the percentage of CD8+CD38+ subset reached normal values, which were (581 +/- 356)/mm3 and (40.1 +/- 17.6)%, respectively. During the 8th-12th week, the cell counts of CD4+ cell [(578 +/- 193)/mm3] and naive CD4+ subset [(176 +/- 64)/mm3] were still less than those of normal controls, while compared with those of the 1st week, the increments were remarkable. CONCLUSIONS T lymphocytes of SARS patients decreased dramatically but could be obviously resumed in a short time. It will take more than 8-12 weeks for CD4+ cell and naive CD4+ subset to reach to normal levels.


title: A single recombinant anti-RhD IgG prevents RhD immunization: association of RhD-positive red blood cell clearance rate with polymorphisms in the FcgammaRIIA and FcgammaIIIA genes.

text: A single recombinant immunoglobulin G1 (IgG1) anti-RhD antibody (MonoRho) was compared with a currently used polyclonal anti-RhD product (Rhophylac) in a phase 1 study for safety, efficacy of Rhesus D (RhD)-positive red blood cell (RBC) clearance, and prevention of RhD immunization in RhD-negative men challenged with 15 mL RhD-positive RBCs. Both the polyclonal product and recombinant anti-RhD effectively cleared RhD-positive RBCs after intravenous and intramuscular injection. The recombinant anti-RhD demonstrated a slower clearance rate compared with the polyclonal anti-RhD. There was no dose response, and there was considerable variation among subjects who received the same dose of recombinant anti-RhD. Interestingly, RhD-positive RBC clearance rates were strongly associated with Fcgamma receptor IIA (FcgammaRIIA) and FcgammaIIIA but not with FcgammaIIIB polymorphisms. Subjects homozygous for FcgammaRIIA-131H or FcgammaRIIIA-158V allotypes showed a faster clearance rate compared with both the heterozygote and the corresponding alternative homozygote allotypes. A similar but less marked trend was seen for the polyclonal anti-RhD. Despite the variation in clearance rates there was no evidence of anti-RhD alloantibodies in any of the subjects at +6 months after the RBC challenge.


title: Characterization and complete genome sequence of a novel coronavirus, coronavirus HKU1, from patients with pneumonia.

text: Despite extensive laboratory investigations in patients with respiratory tract infections, no microbiological cause can be identified in a significant proportion of patients. In the past 3 years, several novel respiratory viruses, including human metapneumovirus, severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV), and human coronavirus NL63, were discovered. Here we report the discovery of another novel coronavirus, coronavirus HKU1 (CoV-HKU1), from a 71-year-old man with pneumonia who had just returned from Shenzhen, China. Quantitative reverse transcription-PCR showed that the amount of CoV-HKU1 RNA was 8.5 to 9.6 x 10(6) copies per ml in his nasopharyngeal aspirates (NPAs) during the first week of the illness and dropped progressively to undetectable levels in subsequent weeks. He developed increasing serum levels of specific antibodies against the recombinant nucleocapsid protein of CoV-HKU1, with immunoglobulin M (IgM) titers of 1:20, 1:40, and 1:80 and IgG titers of <1:1,000, 1:2,000, and 1:8,000 in the first, second and fourth weeks of the illness, respectively. Isolation of the virus by using various cell lines, mixed neuron-glia culture, and intracerebral inoculation of suckling mice was unsuccessful. The complete genome sequence of CoV-HKU1 is a 29,926-nucleotide, polyadenylated RNA, with G+C content of 32%, the lowest among all known coronaviruses with available genome sequence. Phylogenetic analysis reveals that CoV-HKU1 is a new group 2 coronavirus. Screening of 400 NPAs, negative for SARS-CoV, from patients with respiratory illness during the SARS period identified the presence of CoV-HKU1 RNA in an additional specimen, with a viral load of 1.13 x 10(6) copies per ml, from a 35-year-old woman with pneumonia. Our data support the existence of a novel group 2 coronavirus associated with pneumonia in humans.


title: Acute renal failure in patients with severe acute respiratory syndrome.

text: BACKGROUND AND PURPOSE Severe acute respiratory syndrome (SARS) is caused by a new coronavirus, and results in respiratory failure. Acute renal failure (ARF) may also occur and/or complicate the disease course, however, its incidence, causes and impact in SARS patients are not known. METHODS ARF patients were identified from a total of 78 (33 men and 45 women) probable SARS cases admitted to a single hospital. The clinical features of patients with ARF were characterized, and the etiologies analyzed. RESULTS Patients were assigned to ARF (n = 13; 17%) and non-ARF groups (n = 65). Patients with ARF were older than their non-ARF counterparts. ARF developed 7.2 +/- 4.3 days after admission. The incidence of ARF was higher in males (77% vs 35%; p < 0.05). Comorbidities of diabetes and heart failure were more common in patients who developed ARF (38% vs 6%, p < 0.01 and 38% vs 2%, p < 0.001, respectively) and the incidence of respiratory failure (85% vs 26%, p < 0.001) and mortality (77% vs 8%, p < 0.001) were also higher. Multiple organ system failure usually accompanied ARF. Hypotension (77%) caused by nosocomial infections, gastrointestinal bleeding, or SARS per se, and rhabdomyolysis (43%) was associated with ARF in addition to pre-renal factors. Five patients in the ARF group and 1 female patient with end-stage renal failure underwent renal replacement therapy during hospitalization; however, both eventually died. Of the 16 medical staff performing renal replacement therapy, none was subsequently infected with SARS coronavirus. CONCLUSIONS Development of ARF during the disease course in SARS patients is associated with catastrophic outcome. The cause of ARF in SARS patients is often associated with pre-renal factors, hypotension, rhabdomyolysis, and previous comorbidities including diabetes and old age. Universal precautions to prevent viral transmission are mandatory for medical staff performing renal replacement therapy.


title: [Transanal endoscopic microsurgery (TEM)].

text: Minimally invasive surgery is mandatory for rectal tumors to reduce surgical complications and to improve the quality of life. The conventional transanal procedure is one from of minimally invasive surgery for rectal tumors, but it is still often difficult to reach the middle and upper thirds of the rectum due to anatomical characteristics. Transanal endoscopic microsurgery (TEM) is a technique that allows radical resection of rectal tumors in the distal as well as proximal third of the rectum. Performing radical surgery using this technique requires preoperative estimation of tumor extension both histologically and by X-ray images. It should allow provide safe and radical excision of rectal tumors. In our department, patients with rectal tumors are evaluated for risk factors using barium enema, endoscopic ultrasound, punch biopsy, etc. Fifty patients (rectal cancer, 34: cartinoid, 4: adenoma, 12) have undergone radical TEM. The operation was converted to open surgery in 2 cases because of rectal perforation. Radical open surgery was performed after TEM in 1 patient since cancer invasion was revealed by postoperatively upon histological examination. We conclude that TEM is a useful technique for radical resection of rectal tumors and is associated with a low rate of postoperative complications and a high surgical success rate.