title: [Severe acute respiratory syndrome (SARS)--new, unknown disease?].

text: Severe Acute Respiratory Syndrome (SARS) caused by new corona--virus SARS-Co-V was not identified at humans and animals up to this time. A characteristic feature of this disease is biphasic course. First high fever, parainfluenza syndrome followed by increasing respiratory distress. The main role in transmission is droplet way, things contaminated by excreta, blood transfusion is not excluded. Pathomorphological changes are: bronchial epithelial denudation, loss of cilia, squamous metaplasia, a giant cells infiltrate of macrophages in the alveoli, haemophagocytosis, atrophy white pulp of the spleen. Diagnosis is based on clinical picture and epidemiological data supported by positive serology, PCR or presence virus in cell culture. In treatment ribavirin, steroids and mechanical ventilation are used.


docid: uzkvgxjr

title: [Rhinovirus and acute bronchiolitis in young infants].

text: OBJECTIVE To determine the prevalence of rhinovirus infection in hospitalized young infants with acute bronchiolitis. METHODS Hospitalized children with acute bronchiolitis admitted to the Hospital São Lucas/PUCRS between May and September 2002 were selected prospectively. Nasopharyngeal samples were assayed for respiratory syncytial virus, parainfluenza, influenza and adenovirus by immunofluorescence. For rhinovirus test a reverse transcription-polymerase chain reaction for picornavirus was used, followed by hybridization with rhinovirus specific probes. RESULTS Forty-five patients were selected for the study. The median age of the subjects studied was 2 months. Positive samples for respiratory viruses were found in 35/45 (77.8%) subjects and 7/35 (20%) patients had dual infection. Respiratory syncytial virus was detected in 33/35 (94%) cases. Rhinovirus was detected in 6/35 patients (17%). CONCLUSIONS Rhinovirus was the second most common agent detected in nasal secretions from young infants hospitalized with acute bronchiolitis.


title: Insights on biology and evolution from microbial genome sequencing.

text: No field of research has embraced and applied genomic technology more than the field of microbiology. Comparative analysis of nearly 300 microbial species has demonstrated that the microbial genome is a dynamic entity shaped by multiple forces. Microbial genomics has provided a foundation for a broad range of applications, from understanding basic biological processes, host-pathogen interactions, and protein-protein interactions, to discovering DNA variations that can be used in genotyping or forensic analyses, the design of novel antimicrobial compounds and vaccines, and the engineering of microbes for industrial applications. Most recently, metagenomics approaches are allowing us to begin to probe complex microbial communities for the first time, and they hold great promise in helping to unravel the relationships between microbial species.


title: Redox regulation in the extracellular environment.

text: The oxidizing nature of the extracellular environment is vastly different from the highly reducing nature of the intracellular compartment. The redox potential of the cytosolic compartment of the intracellular environment limits disulfide bond formation, whereas the oxidizing extracellular environment contains proteins rich in disulfide bonds. If not for an extracellular antioxidant system to eliminate reactive oxygen and nitrogen species, lipid peroxidation and protein oxidation would become excessive, resulting in cellular damage. Many reviews have focused on the role of intracellular antioxidants in the elimination of oxidative stress, but this one will focus on the coordinated action of both intracellular and extracellular antioxidants in limiting cellular oxidant stress.


title: Isotype- and subclass-specific responses to infection and reinfection with parainfluenza-3 virus: comparison of the diagnostic potential of ELISAs detecting seroconversion and specific IgM and IgA.

text: Isotype- and subclass-specific indirect enzyme-linked immunosorbent assays were developed to detect parainfluenza-3 virus-specific IgG1, IgG2, IgM, and IgA responses. Sera were treated with protein G-agarose prior to testing for specific IgM and IgA to eliminate the possibility of false-positive results due to IgM-rheumatoid factor and to remove interisotypic competition due to specific IgG. IgM and IgA absorbance values were expressed as a percentage of the absorbance values of positive reference sera included on each plate (S/P%), and respective positive/negative threshold values of 15.0% and 28.0% were determined. The mean interval between experimental infection of 3 calves and initial detection of specific IgG1 and IgG2 responses was 8.0 and 9.3 days respectively, rising rapidly to an initial plateau 13.7 and 11.0 days postinfection (dpi). Reinfection of these calves at 30 dpi resulted in further rapid increases, with higher plateau values reached 13.0 (IgG1) and 13.7 (IgG2) days later. The mean interval between infection and the first positive IgM and IgA responses was 6.7 and 12.3 days, respectively. IgM S/P% values peaked at 13.0 dpi, with all 3 calves showing a secondary anamnestic response to reinfection, peaking 4.7 days later. The IgA response to initial infection was weak, with only 2 calves showing an obvious peak response at 15.0 dpi. A strong anamnestic IgA response to reinfection occurred in 2 calves, with a peak response 9.5 days later. Apparent biphasic and triphasic IgM and IgA responses were evident in some calves. Acute and convalescent serum samples from 80 calves involved in 17 outbreaks of respiratory disease were tested for specific IgM and IgA. Positive IgM results were detected in 15 outbreaks, with 71 sera from 44 calves testing positive. Although IgA-positive results were detected in the same 15 outbreaks, only 42 sera from 31 calves were positive. In a previous study, seroconversion was detected in 21 of these calves from 10 outbreaks. Thus the diagnostic potential of the assays was in the order IgM > IgA > seroconversion. The correlations between IgM and IgA, IgM and seroconversion, and IgA and seroconversion results for each calf were 73.8%, 58.8% and 62.5%, respectively.


title: [Dynamic changes of plasma cytokine levels in patients with severe acute respiratory syndrome].

text: OBJECTIVE To elucidate the mechanism of strong inflammatory response in severe acute respiratory syndrome (SARS) patients. METHODS 24 patients managed with a standard corticosteroid protocol developed by Peking Union Medical College Hospital were followed up for 2 months and their clinical outcomes were documented. Plasma levels of interleukin (IL)-1 beta, IL-2, IL-4, IL-8, IL-10, IL-12 p70, interferon gamma (IFN gamma), and tumor necrosis factor alpha (TNF alpha) were determined by quantitative ELISA during the course of disease respectively. 12 healthy blood donors were used as normal controls. RESULTS All SARS patients had remarkably increased plasma IL-8 concentrations (median 31.23 ng/L) at the onset of disease compared with those of normal controls (6.28 ng/L, P < 0.01). Along with the course of disease IL-8 concentration kept going up and 75% (18/24) patients reached a peak median concentration of 149.65 ng/L (P < 0.01) at the third and fourth weeks. IL-8 came back to normal control levels one month after discharged from hospital. Meanwhile, SARS patients also showed high a TNF alpha level (median 23.12 ng/L) (P < 0.01) at the second week and reached a peak median of 136.35 ng/L (P < 0.05) at the third an fourth weeks. One month after discharged from hospital the plasma TNF alpha concentration fell down to a median of 94.88 ng/L, but it was still much higher than normal controls (3.77 ng/L, P < 0.01). CONCLUSION The SARS-associated coronovirus infection may cause complex cytokine cascade. IL-8 and TNF alpha probably play important roles in mediating strong inflammatory response, which are thought to be responsible for lung injury in SARS patients.


title: The viral bronchiolites diagnosis in children by PCR multiplex.

text: The aim of the study was to determine the etiology of the viral bronchiolites in children by using direct immunofluorescence test and 3 RT-PCR Multiplex (S.Bellau-Pujol) The study was performed on 122 nasal inspirations collected from 3 weeks-6 month old children hospitalizated in the pediatrics service of CH Rouen. The results were that the majority (53%) of bronchiolites in children had like etiology RSV and a lot of these infections had double viral etiology (26% RSV+ Rhinovirus; 2,7% RSV+HMPV and 1% RSV+Coronavirus 229E). An important viral factor which gives bronchiolitis in children is HMPV (11%). We also find respiratory infections with triple viral etiology: RSV+Influenza A virus + Rhinovirus.


title: State cigarette excise taxes - United States, 2010-2011.

text: Increasing the price of cigarettes reduces the demand for cigarettes, thereby reducing youth smoking initiation and cigarette consumption and decreasing the prevalence of cigarette use in the United States overall, particularly among youths and young adults. The most common way governments have increased the price of cigarettes is by increasing cigarette excise taxes, which currently are imposed by all states and the District of Columbia. To update data on state cigarette excise taxes in 2009, CDC conducted a survey of changes in state cigarette excise taxes during 2010-2011. During that period, eight states increased their cigarette excise taxes, and one state decreased its tax; as a result, the mean state tax increased from $1.34 in 2009 to $1.46 in 2011. Previous evidence indicates that further increases in cigarette excise taxes would be expected to result in further reductions in demand for cigarettes, decreasing smoking and associated morbidity and mortality.


title: The Role of Social Work for Foreign Residents in an Epidemic: The MERS Crisis in the Republic of Korea.

text: This article explores the experiences of foreign residents during the period of the Middle East Respiratory Syndrome (MERS) outbreak in (South) Korea and discusses from a social work perspective the implications of their experiences and their needs. Data were obtained from interviews with 22 foreigners who either live and work or study in Korea. The data were then interpreted using a thematic analysis approach in a multilingual research context. The findings from the study show that foreign residents experienced a wide range of social and psychoemotional difficulties during the MERS health threat. Implications for social work practice in an epidemic emergency are presented.


title: [Morphology of coronaviruses from different species of monkeys in the Sukhumi nursery].

text: The ultrastructure of coronaviruses from 46 out of 111 monkeys examined (baboons, macaques, green monkeys, langurs) was studied by negative staining in homogenates of different parts of the intestinal tract, pancreatic gland, liver, kidneys, lungs, heart, and brain. Because of marked pleomorphism of coronaviruses it is suggested that morphological variants of the viruses may be distinguished. No relationship between pleomorphism of virus particles and species differences of monkeys and their organ pathology was established. Morphological signs distinguishing simian coronaviruses from those of man were noted.


title: Community epidemiology of human metapneumovirus, human coronavirus NL63, and other respiratory viruses in healthy preschool-aged children using parent-collected specimens.

text: OBJECTIVES The purpose of this work was to assess the impact of recently described human metapneumovirus and human coronavirus NL63 compared with other respiratory viruses by using sensitive molecular techniques in a cohort of healthy preschool-aged children. We also aimed to assess the use of parent collection to obtain an adequate respiratory specimen from acutely unwell children in the community. PATIENTS AND METHODS The community epidemiology and burden of human metapneumovirus and other respiratory viruses (influenza A, influenza B, respiratory syncytial virus, parainfluenza viruses, adenoviruses, and picornaviruses) were examined in a cohort of 234 preschool-aged children from Melbourne, Australia, over a 12-month period by using polymerase chain reaction testing. Parents collected a daily symptom diary for the duration of the study and were taught to collect a combined nose-throat swab and complete an impact diary when the study child had an acute respiratory illness. RESULTS The average incidence of acute respiratory illness was 0.48 per child-month for the duration of the study, with a winter peak. Of 543 illnesses with > or = 1 specimen returned, 33 were positive for human metapneumovirus (6.1%) and 18 for human coronavirus NL63 (3.3%). Of all of the viruses for which we tested, human metapneumovirus and human coronavirus NL63 were most strongly linked to child care attendance, occurring in 82% and 78% of infected children, respectively. Picornaviruses were the most commonly identified virus group (269 [49.5%]). Influenza virus and adenovirus illnesses had the greatest impact, with fever in more than three quarters and requiring, on average, > 1 local doctor visit per illness. CONCLUSIONS Recently identified human metapneumovirus and human coronavirus NL63 are important pathogens in community-based illness in children, particularly in those who attend child care. Picornaviruses were detected in half of the nose-throat swabs collected during acute respiratory illness in children but resulted in milder illnesses; influenza and adenovirus caused the highest-impact illnesses. The use of parent-collected specimens should be considered for additional community-based epidemiologic studies and vaccine trials.


title: Can the health-care system meet the challenge of pandemic flu? Planning, ethical, and workforce considerations.

text: The federal pandemic influenza plan predicts that 30% of the population could be infected. The impact of this pandemic would quickly overwhelm the public health and health-care delivery systems in the U.S. and throughout the world. Surge capacity for staffing, availability of drugs and supplies, and alternate means to provide care must be included in detailed plans that are tested and drilled ahead of time. Accurate information on the disease must be made available to health-care staff and the public to reduce fear. Spokespersons must provide clear, consistent messages about the disease, including actions to be taken to contain its spread and treat the afflicted. Home care will be especially important, as hospitals will be quickly overwhelmed. Staff must be prepared ahead of time to assure their ability and willingness to report to work, and public health must plan ahead to adequately confront ethical issues that will arise concerning the availability of treatment resources. The entire community must work together to meet the challenges posed by an epidemic. Identification and resolution of these challenges and issues are essential to achieve adequate public health preparedness.


Nucleotide sequencing of mouse hepatitis virus strain JHM messenger RNA 7.


title: Viruses and exacerbations of chronic obstructive pulmonary disease: unmet clinical need.

text: Chronic obstructive pulmonary disease (COPD) is a non-communicable long-term condition characterised by accelerated lung-function decline and intermittent episodes of respiratory illness called exacerbations. We discuss the current understanding of the role of viruses in these elements of COPD. The burden of acute viral illness in COPD is great and largely unrecognised. Because naturally occurring exacerbations are inherently difficult to study, only recently have we understood underlying pathophysiological mechanisms and the true prevalence of viral exacerbations. Data are also emerging to support a potential role for chronic viral infection in the progression of stable COPD. As knowledge in these two areas develops, it is clear that the role of viruses in COPD represents a significant unmet clinical need.


title: Transmission dynamics of Tasmanian devil facial tumor disease may lead to disease-induced extinction.

text: Most pathogens threatening to cause extinction of a host species are maintained on one or more reservoir hosts, in addition to the species that is threatened by disease. Further, most conventional host-pathogen theory assumes that transmission is related to host density, and therefore a pathogen should become extinct before its sole host. Tasmanian devil facial tumor disease is a recently emerged infectious cancer that has led to massive population declines and grave concerns for the future persistence of this largest surviving marsupial carnivore. Here we report the results of mark-recapture studies at six sites and use these data to estimate epidemiological parameters critical to both accurately assessing the risk of extinction from this disease and effectively managing this disease threat. Three sites were monitored from before or close to the time of disease arrival, and at three others disease was well established when trapping began, in one site for at least 10 years. We found no evidence for sex-specific differences in disease prevalence and little evidence of consistent seasonal variation in the force of infection. At all sites, the disease was maintained at high levels of prevalence (>50% in 2-3-year-old animals), despite causing major population declines. We also provide the first estimates of the basic reproductive rate R0 for this disease. Using a simple age-structured deterministic model, we show that our results are not consistent with transmission being proportional to the density of infected hosts but are consistent with frequency-dependent transmission. This conclusion is further supported by the observation that local disease prevalence in 2-3-year-olds still exceeds 50% at a site where population density has been reduced by up to 90% in the past 12 years. These findings lend considerable weight to concerns that this host-specific pathogen will cause the extinction of the Tasmanian devil. Our study highlights the importance of rapidly implementing monitoring programs to determine how transmission depends on host density and emphasizes the need for ongoing management strategies involving a disease-free "insurance population," along with ongoing field monitoring programs to confirm whether local population extinction occurs.


Mad cow and other maladies: update on emerging infectious diseases.


title: [Diabetes and COVID-19 infection].

text: Based on the epidemiological data currently available, diabetes does not seem to be a risk factor for infection with SARS-CoV-2 but may be associated with a more severe course. Diabetes is extremely common in older patients with co-morbidities who are at risk of unfavorable outcomes. As with any other infection, poorly controlled pre-existing diabetes can promote secondary infections and lead to acute complications related to hyperglycemia, worsened itself by the infection. It is important to advise patients to have enough diabetic equipment and supplies at home, to make regular blood glucose self-tests, and to contact a caregiver immediately in case of glycemic imbalance or signs of infection. Antidiabetic therapy may need adjustments following usual sick day rules. Insulin therapy should be considered to treat any persistent hyperglycemia in patients hospitalized for an acute infection.


title: Clinical course and management of SARS in health care workers in Toronto: a case series.

text: BACKGROUND Severe acute respiratory syndrome (SARS) has only recently been described. We provide individual patient data on the clinical course, treatment and complications experienced by 14 front-line health care workers and hospital support staff in Toronto who were diagnosed with SARS, and we provide follow-up information for up to 3 weeks after their discharge from hospital. METHODS As part of the initial response to the SARS outbreak in Toronto, our health care centre was asked to establish a SARS unit for health care workers who were infected. Patients were admitted to this unit and were closely monitored and treated until they were well enough to be discharged. We prospectively compiled information on their clinical course, management and complications and followed them for 3 weeks after discharge. RESULTS The 11 women and 3 men described here (mean age 42 [standard deviation [SD] 9] years) were all involved in providing medical or ancillary hospital services to patients who were later found to have SARS. Onset of symptoms in 4 of our patients who could clearly identify only a single contact with a patient with SARS occurred on average 4 (SD 3) days after exposure. For the remaining 10 patients with multiple patient contacts, symptom onset followed exposure by a mean of 3.5 (SD 3) days after their exposure. All patients were treated with ribavirin, and all patients received levofloxacin. Many experienced major complications. Dyspnea was present in 12 patients during their stay in hospital, and all developed abnormalities on chest radiograph; 3 patients developed severe hypoxemia (PaO(2) < 50 mm Hg). All patients experienced a drop in hemoglobin. Nine patients had hemolytic anemia. Three patients experienced numbness and tingling in their hands and feet, and 2 developed frank tetany. All 3 had magnesium levels that were less than 0.1 mmol/L. All patients recovered and were discharged home. At a follow-up examination 3 weeks after discharge (5 weeks after onset of illness), all patients were no longer weak but continued to become fatigued easily and had dyspnea on minimal exertion. For 5 patients, chest radiographs still showed residual disease. INTERPRETATION SARS is a very serious illness even in healthy, relatively young people. The clinical course in our patients, all of whom met the case definition for SARS (which requires pulmonary involvement), resulted in dyspnea and, in some individuals, severe hypoxemia. Severe hemolytic anemia may be a feature of SARS or may be a complication of therapy, possibly with ribavirin.


Health preparedness and legacy planning at mass gatherings in the EMR: a WHO perspective.


title: [Clinical experience of high-flow nasal cannula oxygen therapy in severe corona virus disease 2019 (COVID-19) patients].

text: Acute respiratory failure due to acute hypoxemia is the major manifestation in severe coronavirus disease 2019 (COVID-19) induced by severe acute respiratory syndrome coronavirus 2 infection. Rational and effective respiratory support is crucial in the management of COVID-19 patients. High-flow nasal cannula (HFNC) has been utilized widely due to its superiority over other non-invasive respiratory support techniques. To avoid HFNC failure and intubation delay, the key issues are proper patients, timely application and improving compliance. It should be noted that elder patients are vulnerable for failed HFNC. We applied HFNC for oxygen therapy in severe and critical COVID-19 patients and summarized the following experiences. Firstly, to select the proper size of nasal catheter, to locate it at suitable place, and to confirm the nose and the upper respiratory airway unobstructed. Secondly, an initial flow of 60 L/min and 37℃ should be given immediately for patients with obvious respiratory distress or weak cough ability; otherwise, low-level support should be given first and the level gradually increased. Thirdly, to avoid hypoxia or hypoxemia, the treatment goal of HFNC should be maintained the oxygen saturation (SpO2) above 95% for patients without chronic pulmonary disease. Finally, patients should wear a surgical mask during HFNC treatment to reduce the risk of virus transmission through droplets or aerosols.


title: Studies of murine coronavirus DI RNA replication from negative-strand transcripts.

text: The positive-strand transcripts as well as negative-strand transcripts of mouse hepatitis virus (MHV) defective interfering (DI) RNA, when introduced into MHV-infected cells, resulted in DI RNA replication and accumulation. The leader sequence of the majority of DI RNAs that accumulated from the expression of negative-strand DI RNA transcripts with no extra non-MHV nucleotides at the 3' end switched to that of helper virus, whereas this leader sequence switching did not occur in most of the positive-strand DI RNAs that accumulated from the expressed negative-strand DI RNA transcripts with extra non-MHV nucleotides at the 3' end. These data demonstrated that the extra 4 nucleotides at the 3'-end of negative-strand DI RNA transcripts affected leader sequence switching on DI RNA, and indicated that the leader switching probably occurred during positive-strand DI RNA synthesis.


title: Identification and subcellular localization of a 41 kDa, polyprotein 1ab processing product in human coronavirus 229E-infected cells.

text: The translation products of the human coronavirus (HCV) 229E open reading frames 1a and 1b, the polyproteins 1a and 1ab, are processed by virus-encoded proteinases. One of the key enzymes in this process is a chymotrypsin-like enzyme, the 3C-like proteinase. In this study we have identified an ORF 1b-encoded, 41 kDa processing product in HCV 229E-infected cells by using a monoclonal antibody with defined specificity. We show that this polypeptide is released from polyprotein 1ab by 3C-like proteinase-mediated cleavage of the peptide bonds Gln-6110/Gly-6111 and Gln-6458/Ser-6459. Also, we have investigated the subcellular localization of the 41 kDa processing product. Immunofluorescence microscopy revealed a punctate, perinuclear distribution of the 41 kDa polypeptide in infected cells and an identical subcellular localization was observed for three additional pp1ab-derived polypeptides. In contrast, the virus nucleocapsid protein showed a homogeneous cytoplasmic localization.


Challenges for global nursing.


title: Alteration in serum levels of inflammatory cytokines during parainfluenza virus type 1 infection in patients with severe multiple disabilities.

text: An epidemic of parainfluenza virus type 1 (PIV1) infection occurred in a hospital ward housing patients with severe motor and intellectual disabilities. Twenty-three infected patients exhibited persistent high fever for 4-16 days and decreased lymphocyte counts. One-half of the symptomatic patients had increased blood monocyte counts and the other half progressed to bronchitis or pneumonia. We also compared levels of 27 cytokines in the sera of 21 patients during the acute and normal phases of infection. Cytokine levels were measured with a bead immunoassay performed using the Luminex Multiplex System. Serum levels of interleukin (IL)-1Ra, C-C-motif chemokine (CCL) 2, and C-X-C-motif chemokine (CXCL) 10 significantly increased during the acute phase. In contrast, the serum level of CXCL8 decreased slightly. These results suggest the involvement of monocytes/macrophages and respiratory epithelial cells in the initial stage of PIV1 infection. A previous report using nasal wash samples also found a significant increase in levels of CXCL10 during the acute phase. Hence, CXCL10 may be a useful marker of a cytokine storm produced upon viral infection. However, alterations in levels of IL-1Ra, CCL2, and other cytokines differed between the 2 studies, suggesting that the cytokine profile produced systemically at viral infection is different from that produced at mucosal sites. Further analysis is required to clarify the mechanisms underlying cytokine production during PIV1 infections.


docid: rgedwzsi

title: Reinventing mass communication: a World Health Organization tool for behavioral change to control disease.

text: Most of the WHO's vertical programs, because they were ill-conceived, ill-designed, and defectively implemented, have fallen far short of expectations. These limitations have been doggedly ignored by the WHO, although the authorities in India have now realized that such vertical programs are expensive and not sustainable. Launching of Communication for Behavioral Impact (COMBI) appears to mark a desperate effort to revive their performance. It represents yet another deviation from the mandate given to the WHO. In 1983, the then director general warned against motivational manipulation of people to sell health ideas, but the WHO has now brazenly come forward to look for help from the private sector. COMBI uses the jargon and language of the market place to "market" health programs; it calls this "cause-related marketing." The WHO has been most a historical in conceptualizing COMBI, as it has not learned from the failure of UNICEF's earlier venture to market child survival by employing experts in social marketing to bring about "community mobilization." The WHO should have reviewed the large body of literature on work in the health social sciences, health education, and the many programs based on the concept of "information, education, and communication." The pointed neglect of such key issues raises serious moral, ethical, and human rights questions. The COMBI approach amounts to be a breach of trust--a threat to human dignity.


docid: hmswnrgg

title: Structure of SARS coronavirus spike receptor-binding domain complexed with receptor.

text: The spike protein (S) of SARS coronavirus (SARS-CoV) attaches the virus to its cellular receptor, angiotensin-converting enzyme 2 (ACE2). A defined receptor-binding domain (RBD) on S mediates this interaction. The crystal structure at 2.9 angstrom resolution of the RBD bound with the peptidase domain of human ACE2 shows that the RBD presents a gently concave surface, which cradles the N-terminal lobe of the peptidase. The atomic details at the interface between the two proteins clarify the importance of residue changes that facilitate efficient cross-species infection and human-to-human transmission. The structure of the RBD suggests ways to make truncated disulfide-stabilized RBD variants for use in the design of coronavirus vaccines.


title: Monoclonal antibodies to the peplomer glycoprotein of coronavirus mouse hepatitis virus identify two subunits and detect a conformational change in the subunit released under mild alkaline conditions.

text: Monoclonal antibodies (MAbs) directed against the E2 glycoprotein of mouse hepatitis virus (MHV) have been classified according to their ability to bind to either of the two purified 90,000-molecular-weight subunits (90K subunits) of the 180K peplomeric glycoprotein E2. Correlation with previously reported information about these MAbs suggest that both of the subunits of E2 are important for viral infectivity and cell fusion. Incubation of trypsin-treated virions at pH 8.0 and 37 degrees C released only the E2N subunit from virions. The pattern of MAb reactions suggested that a conformational change occurred in the E2N subunit in association with its release from virions under mildly alkaline conditions at 37 degrees C, the same conditions which are optimal for coronavirus-induced cell fusion.


title: The course of C-reactive protein response in untreated upper respiratory tract infection.

text: BACKGROUND High C-reactive protein (CRP) values are frequently found in patients with bacterial respiratory infection, and CRP testing has been shown to be useful in differentiating pneumonia from other respiratory infections. Raised CRP values may also be found in viral respiratory infection, and as a result there is a risk that antibiotics may be wrongly prescribed. AIMS To describe the course of the CRP response during untreated upper respiratory tract infections and associations between the development of CRP values, erythrocyte sedimentation rate (ESR) and respiratory symptoms. DESIGN OF STUDY Prospective study. SETTING Seven general practices in northern Norway. METHOD Patients with upper respiratory tract infection aged 16 years or over, who were not treated with antibiotics and who had been ill for no more than 3 days, were recruited. Microbiological examinations were undertaken, together with measurements of CRP, ESR and recording of symptoms daily during the first week of illness and on days 10, 14 and 21. RESULTS An aetiological agent was established in 23 of the 41 included subjects. These were: influenza A, influenza B, rhinovirus, and other agents. Among the 15 patients examined on both the second and the third day of illness, the median CRP value increased from 7-10 mg/l, and the mean value was from 19-24 mg/l between day 2 and day 3. Peak CRP values were reached on days 2 to 4. Higher CRP values were found in those infected with influenza A and B than in the other subjects (P <0.001). A CRP value >10 mg/l was found in 26 subjects during the first 7 days, compared to five subjects after 1 week. Evidence of a secondary infection with group A streptococci was found in two of these five subjects. The development of the symptoms of sore throat, fatigue, clamminess, and pain from muscles and joints followed a similar course as the CRP response, while stuffy nose, cough, sputum production, and dyspnoea tended to persist after the CRP values had approached the normal range. CONCLUSION A moderately elevated CRP value (10-60 mg/l) is a common finding in viral upper respiratory tract infection, with a peak during days 2-4 of illness. Moderately elevated CRP values cannot support a diagnosis of bacterial infection when the illness has lasted less than 7 days, but may indicate a complication of viral infection after a week.


title: Virus isolations from patients in general practice, 1961-71.

text: During the period 1961-71 of 1785 viruses isolated from patients in the general population 503 (28%) were rhinoviruses, 465 (26%) influenza viruses, 248 (14%) enteroviruses, 234 (13%) herpes simplex virus, 132 (7%) parainfluenza viruses, 129 (7%) adenoviruses and 49 (3%) respiratory syncytial virus. Also isolated were 18 strains of mumps virus, 7 coronaviruses and 295 streptococci of groups A, C or G.Fluctuations were observed in the frequency with which respiratory syncytial virus, parainfluenza virus type 2, and the adenoviruses were isolated over the 10-year period.Influenza viruses types A and B, parainfluenza viruses types 1 and 2, respiratory syncytial virus, adenoviruses types 3, 4, 6, 7 and 21, and many enteroviruses were all associated with outbreaks.Infections with influenza viruses A and B and parainfluenza viruses types 1 and 2 came during the winter, whereas those with parainfluenza virus type 3, enteroviruses, and rhinoviruses were more frequently seen in the summer and early autumn.


title: Positive rate of serum SARS-CoV immunoglobulin G antibody among healthcare workers.

text: We evaluated the positive rate for severe acute respiratory syndrome (SARS) -CoV IgG antibody among Taiwanese healthcare workers (HCWs). A retrospective cohort research was performed in 2 teaching hospitals and 2 non-teaching hospitals. SARS-CoV IgG antibodies were checked and a structured questionnaire was prepared. A total of 2512 sets of questionnaires was distributed with a return rate of 87.5% (2197 sets). 882 of the respondents had contact with SARS patients. Among 2197 subjects studied, a total of 9 subjects (0.4%) displayed positive findings for SARS-CoV IgG antibody. The relative risk (RR) of contracting SARS for HCWs in the emergency room (ER) was estimated to be 25.94 times greater than the corresponding risk for those HCWs who worked in the ordinary ward (95% CI 7.07-95.14, p<0.001). If we estimated the HCWs who came into contact with SARS patients, the RR for positive serum IgG antibody titer among HCWs from the ER was significantly greater than it was for those working in the ordinary ward (RR 9.45, 95% CI 2.58-34.64, p=0.001). In conclusion, HCWs from the ER faced a relatively high risk for potential infection by the SARS virus when caring for patients who had not been diagnosed with SARS.


title: Heterologous expression of SARS-CoV ORF10 and X5 genes in E. coli and Streptomyces lividans TK24.

text: In previous studies a variety of novel accessory genes has been identified that were interspersed among the structural genes of the SARS-CoV (severe acute respiratory syndrome coronavirus) genome. The predicted unknown proteins (PUPs) encoded by the accessory genes, which are considered to be unique to the SARS-CoV genome, might play important roles in the SARS-CoV infection. Two of these genes, called ORF10 and X5, were synthesized and introduced into E. coli and Streptomyces lividans TK24, respectively. SDS-PAGE and Western blot revealed that the ORF10 and X5 genes have been expressed in the two hosts. This is the first report of heterologous expression of ORF10 and X5 genes in E. coli and S. lividans TK24. This work makes it possible to study the structure and potential functions of proteins encoding by these two genes.


title: Lactococcus lactis anchoring avian infectious bronchitis virus multi-epitope peptide EpiC induced specific immune responses in chickens.

text: Mucosal immunity is critical in preventing infectious bronchitis virus (IBV) infection. To deliver viral antigens to the mucosal immune system of chickens safely and effectively, we constructed a Lactococcus lactis strain carrying IBV multi-epitope gene EpiC fused with the gene of the cell-wall anchoring domain of Staphylococcus aureus protein A. SDS-PAGE and Western blot results indicated that the fused peptide was located partially on the cell surface. Oral and nasal inoculation with the recombinant L. lactis of chickens elicited significantly high humoral and mucosal immune responses, especially in the nasally immunized group. Eighty percent chickens of the nasally immunized group with recombinant L. lactis did not show any clinical signs after a lethal dose challenge with IBV SAIBk strain, while all the non-recombinant L. lactis immunized chickens exhibited obvious and typical symptoms. These results indicate that needle-free recombinant lactococci anchoring the IBV antigen makes a promising vaccine candidate against the spread of IB.


US pacemaker manufacturer faces British lawsuit.


title: [Rational use of respiratory protective equipment: advice for health care professionals in time of COVID-19].

text: The current COVID-19 pandemic has led to a worldwide shortage of respiratory protective equipment. In order to offer maximum protection against infection for all healthcare workers, we need to optimise our use of the available equipment. This article provides practical advice on which type of mask is indicated in what specific situation, what requirements the mask should meet and how to optimise the local workflow, including the re-use of masks after decontamination.


The European Network for Diagnostics of Imported Viral Diseases (ENIVD)--12 years of strengthening the laboratory diagnostic capacity in Europe.


title: [Corona- and rotavirus enteritis in newborn calves in Bulgaria].

text: In the course of investigations into enteritis enzootics in newly-born calves, 55 fecal samples have been studied through direct electron microscopy by the negative contrast method. Rota viruses were found in eight of them, corona viruses in 38.2 per cent of the cases, and both rota- and corona viruses in 49.1 per cent of the cases. Two types of rota-viral particles were observed: with and without supercapsids. Also two types of corona-viral particles were established. The first type was relatively monomorphic, having an average diameter of 120 nm, and length of the surface spikes of 20 nm. The second type was pleomorphic with length of the spikes of 11 nm. Most of the fecal samples, containing corona viruses, agglutinate mice, rat and hamster erythrocytes. On studying the physical and chemical properties of the hemagglutinine, ist gradient density and antigenic patterns it was shown that it is related to the intact corona-virions. With the hemagglutination-inhibition test developed, antibodies against corona-viruses in the sera of a considerable number of the cows have been demonstrated. A precipitating antigen has been shown in a part of the fecal samples, containing rota-viruses. By studying the physical and chemical properties, its gradient density and its comparison with a refernce antigen, it has been shown that the antigen was conditioned by degraded fragments of rota-viruses. With the aid of the immunodiffusion method with a fecal antigen evolved, precipitating antibodies have been shown in 18 to 46 per cent of the cows and calves.


Immunization and health workers: overview.


title: Detection of equine rotavirus by reverse transcription loop-mediated isothermal amplification (RT-LAMP).

text: Reverse transcription loop-mediated isothermal amplification (RT-LAMP) was applied to detection of equine rotavirus. Because equine rotavirus of the single P genotype, P[12], is predominant in the equine population worldwide, an RT-LAMP primer set was designed to target the genotype P[12] sequence and thus detect equine rotavirus. The detection limit of the RT-LAMP assay was 10(3) copies of viral RNA, whereas that of semi-nested RT-PCR for genotype P[12] was 10(5) copies. The RT-LAMP assay specifically amplified genotype P[12] but did not amplify the other P genotype strains. The RT-LAMP assay did not amplify any pathogens related to equine intestinal disorder other than rotavirus. Using 96 diarrheal stools, the RT-LAMP assay detected equine rotavirus in 58 samples, whereas semi-nested RT-PCR only detected equine rotavirus in 25 samples. The RT-LAMP assay did not detect equine rotavirus with fecal samples collected from nine healthy foals. These results indicate that the RT-LAMP assay is specific for equine rotavirus and more sensitive than semi-nested RT-PCR. Because it is easy to manipulate without the need for a thermal cycler or gel electrophoresis, the RT-LAMP assay should be applicable to diagnosis of equine rotavirus infections in diagnostic laboratories.


Antibodies to viruses of human origin in monkeys from Uganda.


title: Characterization of the sialic acid binding activity of transmissible gastroenteritis coronavirus by analysis of haemagglutination-deficient mutants.

text: Transmissible gastroenteritis coronavirus (TGEV) agglutinates erythrocytes of several species by virtue of sialic acid binding activity of the surface protein S. We have isolated and characterized five haemagglutination-defective (HAD) mutants. In contrast to the parental virus, the mutants were unable to bind to porcine submandibulary mucin, a substrate rich in sialic acid. Each of the mutants was found to contain a single point mutation in the S protein (Cys155Phe, Met195Val, Arg196Ser, Asp208Asn or Leu209Pro), indicating that these amino acids are affecting the sialic acid binding site. In four of the HAD mutants a nearby antigenic site is affected in addition to the sialic acid binding site, as indicated by reactivity with monoclonal antibodies. The parental virus was found to have an increased resistance to the detergent octylglucoside compared to the HAD mutants. This effect depended on cellular sialoglycoconjugates bound to the virion. If the binding of sialylated macromolecules was prevented by neuraminidase treatment, the parental virus was as sensitive to octylglucoside as were the HAD mutants. We discuss the possibility that the sialic acid binding activity helps TGEV to resist detergent-like substances encountered during the gastrointestinal passage and thus facilitates the infection of the intestinal epithelium. An alternative function of the sialic acid binding activity - accessory binding to intestinal tissues - is also discussed.


Characterization of monoclonal antibodies to human OC43.


title: [Transgenic potato containing immunogenic gene of avian coronavirus and its immunogenicity in mice].

text: To check the feasibility of expression of the immunogenic gene of avian coronavirus infectious bronchitis virus (IBV) in plants, the transformation of S1 gene of IBV into potato and the immunogenicity of its expression product was studied. The S1 gene of IBV-ZJ971 strain was inserted into plasmid pBI121 under the control of 35 S promoter. Agrobacterium fumefaciens EHA105 with the recombinant vector pBI121 was obtained by tri-parental mating method. So, an efficient potato transformation system mediated by Agrobacterium fumefaciens was established. The rates of calli and shoots differentiation were 100%, and more than 95% respectively, for transgenic potato with S1 gene of IBV. PCR and Southern blot analyses showed that IBV S1 gene was integrated into genomic DNA of the potato plant and most transgenic plants had two copies of S1 gene of IBV. In our experiments, 47 transgenic plantlets have been obtained. Northern blot and ELISA analyses indicated that most transgenic plants could normally transcribe and translate S1 gene of IBV, though the levels of transcription and translation were different in various transgenic plants. Immunity assay with BALB/C mice showed that expression products of transgenic potato with S1 gene of IBV were immunogenic, and ELISA antibody titer reached 1:20 to 1:40 and 1:80 to 1:160 with doses of 0.5 g and 1 g, respectively. Virus neutralization (VN) antibodies were detected by tracheal organ cultures, and the results showed that VN titers reached respectively 1:160 to 1:320 and 1:320 to 1:2048 with doses of 0.5 g and 1 g.


title: Seroepidemiology of respiratory (group 2) canine coronavirus, canine parainfluenza virus, and Bordetella bronchiseptica infections in urban dogs in a humane shelter and in rural dogs in small communities.

text: This prospective study evaluated seroepidemiologic features of canine respiratory coronavirus (CRCoV), canine parainfluenza virus (CPIV), and Bordetella bronchiseptica infections in dogs in an urban humane shelter and in rural/small community dog populations in western Canada. Seroprevalence of CRCoV and CPIV was low compared with other countries; seroprevalence of B. bronchiseptica was moderate to high in most populations examined. Rural dogs were 0.421 times (P ≤ 0.0001) less likely to be positive for CRCoV than dogs admitted to the shelter. There were no statistical differences in prevalence of antibodies to B. bronchiseptica and CPIV between urban and rural populations. Dogs from Fort Resolution, NWT were significantly (P < 0.05) less likely to have moderate or high antibody titers to the 3 agents than dogs in the shelter. Seroconversion to CRCoV was common in dogs in the shelter, but was not associated (P = 0.18) with respiratory disease. Antibodies to CRCoV, CPIV, or B. bronchiseptica on arrival were not significantly (P > 0.05) associated with disease-sparing after entry into the shelter.


title: Pilot prospective open, single-arm multicentre study on off-label use of tocilizumab in severe patients with COVID-19.

text: OBJECTIVES No agent has yet been proven to be effective for the treatment of severe patients with COVID-19. METHODS We conducted a pilot prospective open, single-arm multicentre study on off-label use of tocilizumab (TCZ) involving 63 hospitalised adult patients (56 males, age 62.6±12.5) with severe COVID-19. Clinical and laboratory parameters were prospectively collected at baseline, day 1, 2, 7 and 14. No moderate-to severe adverse events attributable to TCZ were recorded. RESULTS We observed a significant improvement in the levels of ferritin, C-reactive protein, D-dimer. The ratio of the partial pressure of oxygen (Pa02) to the fraction of inspired oxygen (Fi02) improved (mean±SD Pa02/Fi02 at admission: 152±53; at day 7: 283.73 ± 115.9, at day 14: 302.2 ± 126, p<0.05). The overall mortality was 11%; D-dimer level at baseline, but not IL-6 levels were predictors of mortality. TCZ administration within 6 days from admission in the hospital was associated with an increased likelihood of survival (HR 2.2 95%CI 1.3-6.7, p<0.05). CONCLUSIONS In hospitalised adult patients with severe COVID-19, TCZ could be a safe option. An improvement in respiratory and laboratory parameters was observed. Future controlled trials in patients with severe illness are urgently needed to confirm the definite benefit with IL-6 target therapy.


title: Factors that distinguish college students with depressive symptoms with and without suicidal thoughts.

text: BACKGROUND Suicide among college students is a significant public health concern. Although suicidality is linked to depression, not all depressed college students experience suicidal ideation (SI). The primary aim of this study was to determine potential factors that may distinguish college students with depressive symptoms with and without SI. METHODS A total of 287 undergraduate college students with substantial depressive symptoms (Beck Depression Inventory [BDI] total score >13) with and without SI were compared across psychiatric and functional outcome variables. Independent sample t tests were conducted for each outcome variable using the suicide item of the BDI as a dichotomous (ie, zero vs nonzero score) grouping variable. RESULTS Relative to students with substantial depressive symptoms without SI, those with SI were more symptomatic overall, having significantly higher levels of depressive symptoms, hopelessness, and anxiety. However, contrary to our expectations, nonsuicidal and suicidal students did not differ on measures of everyday functioning (ie, cognitive and physical functioning and grade point average). CONCLUSIONS Our findings suggest that SI among college students is associated with increased subjective distress but may not adversely impact physical or cognitive functioning or academic performance.


title: Receptor for mouse hepatitis virus is a member of the carcinoembryonic antigen family of glycoproteins.

text: The receptor for mouse hepatitis virus (MHV), a murine coronavirus, is a 110- to 120-kDa glycoprotein on intestinal brush border membranes and hepatocyte membranes. The N-terminal 25-amino acid sequence of immunoaffinity-purified MHV receptor was identical to the predicted mature N termini of two mouse genes related to human carcinoembryonic antigen (CEA) and was strongly homologous to the N termini of members of the CEA family in humans and rats. Polyclonal antibodies to human CEA recognized the immunoaffinity-purified MHV receptor and the MHV receptor in liver membranes and intestinal brush border membranes from MHV-susceptible mouse strains. In membranes from MHV-resistant SJL/J mice, the anti-CEA antibodies recognized a homologous glycoprotein that failed to bind MHV. The MHV receptor glycoprotein was detected in membranes of BALB/c colon, small intestine, and liver, which are the principal targets for MHV replication in vivo. The MHV receptor glycoprotein resembled members of the human CEA family in molecular weight, acidic pI, extensive glycosylation, solubility in perchloric acid, and tissue distribution. Thus, the MHV receptor is, to our knowledge, the first member of the CEA family of glycoproteins to be identified as a virus receptor.


Multiple sclerosis in twins.


title: Prospective study of respiratory viral infections in pediatric hemopoietic stem cell transplantation patients.

text: BACKGROUND Community-acquired respiratory viruses are an important cause of respiratory disease in pediatric patients undergoing hemopoietic stem cell transplantation. However, there are no studies examining the impact of more rapid and sensitive diagnosis by real time polymerase chain reaction (PCR) in this population. We performed a prospective study to assess the impact of real time PCR diagnosis as well as protective isolation for community-acquired respiratory virus infections in pediatric patients undergoing hemopoietic stem cell transplantation. METHODS During a 2-year period, 39 pediatric patients undergoing hemopoietic stem cell transplantation were analyzed for presence of respiratory viruses. Samples were taken at regular intervals and analyzed by culture and newly developed real time PCR methods. All patients were cared for in protective isolation. RESULTS Respiratory symptoms were observed in 10 of the 39 cases (26%) and a virus was identified in 8 and 6 of these cases by PCR and culture, respectively. The PCR detected the respiratory infection a median of 8 days before culture. However, the morbidity of the respiratory infections was generally mild, and no mortality was observed. Additionally all infections were observed pretransplant or after discharge; no nosocomial infections were observed. CONCLUSIONS The real time PCR assay is more rapid and sensitive than culture and could be used to screen patients before transplant or as respiratory symptoms present for timely diagnosis.


title: A serologic survey for antibodies to three canine viruses in wolverines (Gulo gulo) from the Brooks Range, Alaska.

text: Canine distemper virus (CDV), canine parvovirus type 2 (CPV-2), and canine adenovirus type 1 (CAV-1) are pathogens that are typically associated with canids but may cause serious disease in a wide range of other carnivores. From 1998 to 2002, serum samples from 64 wolverines (Gulo gulo) from the Brooks Range, Alaska, were tested for antibodies to CDV, CPV-2, and canine adenovirus (CAV). Four animals tested positive for antibodies to CDV (7%), one for antibodies to CPV-2 (2%), and none for antibodies to CAV. These are similar to antibody prevalence estimates for other large and medium carnivores in North America.


title: Transcriptional profiling of host responses in mouse lungs following aerosol infection with type A Francisella tularensis.

text: Tularaemia caused by inhalation of type A Francisella tularensis bacteria is one of the most aggressive infectious diseases known, but the reasons for the very rapid spread of the organism from the lungs to internal organs and the ensuing mortality are unknown. The present study used the mouse model to examine in detail the host immune response in the lung. After an aerosol challenge with 20 c.f.u. of the type A strain FSC033, all mice developed clinical signs of severe disease, showed weight loss by day 4 of infection and died the next day. Histopathological findings in the lung revealed acute inflammation and intense vasculitis and perivasculitis on day 4. Gene transcriptional changes in the mouse lung samples were examined on days 1, 2 and 4 of infection using a cDNA microarray with 20,600 mouse clones representing 18,500 genes. In total, 424 genes were found to be differentially expressed, some of which were both up- and downregulated at different time points, 192 of which were upregulated and 234 of which were downregulated for at least one time point. A high percentage of selected genes identified by the microarray analysis were confirmed to be differentially regulated by quantitative real-time PCR. Categorization of the differentially expressed genes showed that those preferentially involved in host immune responses were activated extensively on day 4 but hardly or not at all on days 1 and 2. Further analysis revealed that several of the genes upregulated on day 4 are known to depend on gamma interferon or tumour necrosis factor alpha for their regulation. In keeping with this finding, tumour necrosis factor alpha and gamma interferon levels were found to be increased significantly in bronchoalveolar lavage on day 4.


A novel surgical approach for the treatment of severe alkaline reflux after total gastrectomy and Roux-en-Y reconstruction.


title: [Clinical and epidemiological review of SARS].

text: Severe acute respiratory syndrome (SARS) was caused by a previously unrecognized new type coronavirus. The disease probably first emerged in Guangdong China around November 2002, and it spread from there first to countries in Southeast Asia, and finally throughout the world. During the outbreak, more than 8,000 cases and about 800 deaths had been reported. The first sign of illness in most cases of SARS is fever, headache, malaise, or myalgia, and then majority of patients present severe atypical pneumonia. It appeared that disease spread most often in hospitals in health care workers, and patients and among family members. Given the severity of SARS, clinicians throughout the world empirically treated most patients with corticosteroids and ribavirin.


title: [Expression of SARS spike gene in Shizomycete pombe].

text: The viral spike protein is the main surface antigen of the coronavirus, and it could be useful in the research of clinical diagnosis, SARS vaccine and the structure biology.According to the analysis of the main antigen of the SARS spike protein, 5 fragments of the whole spike gene were cloned, and ligated to the vector pNMT1. Through electroporation transformantion to TCP1, the recombinant S. pombe strains capable of expressing the 5 fragments were constructed. SDS-PAGE or Western blot analysis of the induced expression products demonstrated that the 5 recombinant proteins were expressed in the fission yeast respectively.


title: [Amendment to the infectious disease control law].

text: The Law Concerning the Prevention of Infectious Diseases and Medical Care for Patients of Infections (the Infectious Diseases Control Law) enacted on April 1, 1999, accompanies an additional rule for reconsideration in five years after putting the law in operation and for taking necessary steps when needed. The responses against bioterrorism involving anthrax and smallpox after the terrorist attacks on September 11, 2001, in the United States of America (a notice on October 11, 2001 by the Tuberculosis and Infectious Diseases Control Division, MHLW) and the response to severe acute respiratory syndrome (SARS), an emerging infectious disease upon which a Global Alert was issued on March 12, 2003, by WHO, were discussed. On November 5, 2003, partial amendment of the Infectious Diseases Control Law and the Quarantine Law was approved and put into operation on. In the present amendment, the following three points were principally reconsidered: 1. strengthening infectious disease control in an emergency, particularly the role of national government, 2. reviewing control strategy of infectious diseases of animal origin, and 3. reviewing target diseases of the Infectious Diseases Control Law and categories of infectious diseases.


title: Nephrogenic fibrosing dermopathy associated with exposure to gadolinium-containing contrast agents--St. Louis, Missouri, 2002-2006.

text: Nephrogenic fibrosing dermopathy (NFD) causes thickening and hardening of the skin, often in the extremities, and occurs in patients with underlying renal disease. The skin lesions can progress rapidly, sometimes leading to joint immobility and the inability to walk. In May 2006, nephrologists at hospital A in St. Louis, Missouri, reported to CDC and the Missouri Department of Health and Senior Services (MoDHSS) a cluster of NFD among patients treated in their dialysis units. CDC and MoDHSS conducted an investigation to determine the number of affected patients and identify risk factors for NFD. Thirty-three patients with NFD were identified in St. Louis, 28 of whom had been treated at hospital A. A matched case-control study was conducted at the hospital. This report summarizes the preliminary results of that study, which indicated that exposure to gadolinium-containing contrast agents during magnetic resonance imaging (MRI) studies was independently associated with NFD. Clinicians should be aware of the potential for NFD, and when possible, should avoid use of gadolinium-containing contrast agents in patients with advanced renal disease.


title: Hygromycin B therapy of a murine coronaviral hepatitis.

text: Hepatitis caused by mouse hepatitis virus (MHV-A59), a murine coronavirus, is accompanied by direct infection and replication of virus within the liver. We demonstrate here that the aminoglycoside hygromycin B is able to eliminate MHV-A59 infection from mouse peritoneal macrophages and cultured liver cells in vitro and is also able to reduce levels of virus replication and necrotic liver foci in vivo.


title: S protein of severe acute respiratory syndrome-associated coronavirus mediates entry into hepatoma cell lines and is targeted by neutralizing antibodies in infected patients.

text: The severe acute respiratory syndrome-associated coronavirus (SARS-CoV) causes severe pneumonia with a fatal outcome in approximately 10% of patients. SARS-CoV is not closely related to other coronaviruses but shares a similar genome organization. Entry of coronaviruses into target cells is mediated by the viral S protein. We functionally analyzed SARS-CoV S using pseudotyped lentiviral particles (pseudotypes). The SARS-CoV S protein was found to be expressed at the cell surface upon transient transfection. Coexpression of SARS-CoV S with human immunodeficiency virus-based reporter constructs yielded viruses that were infectious for a range of cell lines. Most notably, viral pseudotypes harboring SARS-CoV S infected hepatoma cell lines but not T- and B-cell lines. Infection of the hepatoma cell line Huh-7 was also observed with replication-competent SARS-CoV, indicating that hepatocytes might be targeted by SARS-CoV in vivo. Inhibition of vacuolar acidification impaired infection by SARS-CoV S-bearing pseudotypes, indicating that S-mediated entry requires low pH. Finally, infection by SARS-CoV S pseudotypes but not by vesicular stomatitis virus G pseudotypes was efficiently inhibited by a rabbit serum raised against SARS-CoV particles and by sera from SARS patients, demonstrating that SARS-CoV S is a target for neutralizing antibodies and that such antibodies are generated in SARS-CoV-infected patients. Our results show that viral pseudotyping can be employed for the analysis of SARS-CoV S function. Moreover, we provide evidence that SARS-CoV infection might not be limited to lung tissue and can be inhibited by the humoral immune response in infected patients.


title: [Gene prediction and function research of SARS-CoV(BJ01)].

text: Through reading the articles, this study points out the shortage of gene prediction and function research about SARS-CoV, and predict it again for developing effective drugs and future vaccines. Using twelve gene prediction methods to predict coronavirus known genes, we select four better methods including Heuristic models, Gene Identification, ZCURVE_CoV and ORF FINDER to predict SARS-CoV(BJ01), and use ATGpr for analyzing probability of initiation codon and Kozak rule, search transcription regulating sequence(TRS) in order to improve the accuracy of predicted genes. Twenty-one probable new genes with more than 50 amino acids have been obtained excluding 13 ORFs which are similar to the genes of NCBI and relative articles. For predicted proteins, we use ProtParam to analyse physical and chemical features; SignalP to analyse signal peptide; BLAST, FASTA to search similar sequences; TMPred, TMHMM, PFAM and HMMTOP to analyse domain and motif in order to improve reliability of gene function prediction. At the same time, we separate the 21 ORFs into four classes using codition of four gene prediction methods, match score, match expection and match length between predicted gene and Coronavirus known gene. In the end, we discuss the results and analyse the reasons.


title: Alterations in the lymphocytic and mononuclear phagocytic systems of turkey poults associated with exposure to poult enteritis and mortality syndrome.

text: In vivo and in vitro mononuclear phagocytic system functions, expression of lymphocyte subset cell surface markers in the thymus and bursa of Fabricius, and lymphocyte subset dynamics during the course of poult enteritis and mortality syndrome (PEMS) were examined. PEMS is an acute, transmissible, infectious intestinal disease accompanied by high mortality and morbidity. The etiology of this multifactorial disease remains to be elucidated; however, turkey coronavirus was initially assumed to be one of the primary agents involved. Further investigation demonstrated that turkey coronavirus was not always detectable in poults exhibiting PEMS symptoms, and, thus, PEMS poults began to be identified as positive or negative for turkey coronavirus. In each trial, uninfected hatchmate controls were compared with turkey poults that were contact exposed to PEMS poults at 7 days of age. Following intravenous inoculation, control poults cleared Escherichia coli from their circulation by 60 min, whereas viable E. coli were still present in the circulation of PEMS poults at 60 min postinoculation. Inflammatory response measured by Sephadex-elicited abdominal exudate cell recruitment and the adherence potential of abdominal exudate cells was not significantly different between uninfected and PEMS poults. The percentage of glass-adherent abdominal exudate macrophages was higher in PEMS poults. However, the ability of these macrophages to phagocytize sheep red blood cells and the average number of sheep red blood cells per phagocytic macrophage were both lower compared with uninfected controls. CD4+ expression in thymic tissue of PEMS poults at 9 days postinfection was significantly lower. The CD4+:CD8+ lymphocyte ratio in peripheral blood leukocytes from coronavirus-negative PEMS poults was lower than that from both uninfected and coronavirus-positive PEMS poults at 14 days postinfection. In the spleen, the CD4+:CD8+ lymphocyte ratio was higher in coronavirus-positive PEMS poults as compared with the other treatments. In conclusion, immune system dysfunction in PEMS is associated with impaired mononuclear phagocytic system function and alterations in lymphocyte populations.


Once-daily edoxaban: a safer option than well-managed warfarin for patients with atrial fibrillation?


title: [Preparatory guidelines for local health services on how to respond to new cases of severe acute respiratory syndrome (SARS)].

text: The Centers for Disease Control and Prevention (CDC) of the United States of America recently issued a set of guidelines on how different community health services should prepare for and respond to the reemergence of severe acute respiratory syndrome (SARS). This document summarizes the recommendations of the CDC for basic health services. Disease surveillance in communities and hospitals should be performed in light of existing information on risk factors, particularly those related to geographic dissemination patterns and to documented transmission of SARS-CoV, the coronavirus that causes SARS. As long as no cases of person-to-person disease transmission are reported anywhere in the world, efforts should be aimed at early detection and notification of cases and of groups of people who are in contact with one another and who have severe respiratory infections of undetermined cause, such as pneumonia, which could signal the reemergence of SARS. If cases of transmission of SARS-CoV have been reported, the aim should be to immediately identify and notify any cases detected in order to take appropriate diagnostic and therapeutic measures and to facilitate outbreak control. The reach of surveillance and reporting activities in specific communities should depend on how widely the disease has spread, both in the community and in local health services. Physicians and public health workers should be familiar with ways to detect SARS cases early, as well as with existing norms for reporting any cases detected.


title: Three-Port Laparoscopic Sleeve Gastrectomy: A Novel Technical Modification.

text: Laparoscopic sleeve gastrectomy has rapidly been adopted as a primary surgical procedure in bariatric patients. The technique of multiport sleeve gastrectomy is described using 4 to 6 ports and an additional port for a liver retractor. A technique of single-port sleeve gastrectomy has been described, the principal advantages of which appear to reduced postoperative pain and an improved cosmetic outcome. In this paper we describe a novel, and easily reproducible technique for the performance of a sleeve gastrectomy using only 3 ports that does not compromise the procedure and may offset the disadvantages of a multiport technique.


title: High-yield expression of recombinant SARS coronavirus nucleocapsid protein in methylotrophic yeast Pichia pastoris.

text: AIM Nucleocapsid (N) protein plays an important role in reproduction and pathological reaction of severe acute respiratory syndrome (SARS) coronavirus (SCoV), the antigenicity of the protein is better than spike (S) protein. This study was to find a highly specific and antigenic recombinant SCoV nucleocapsid (rSCoVN) protein, and to provide a basis for further researches on early diagnosis of SARS. METHODS Full length cDNA of SCoV nucleocapsid (SCoVN) protein was amplified through polymerase chain reaction (PCR) and cloned into yeast expression vector pPIC3.5K to construct plasmid of pPIC3.5K-SCoVN. The plasmid was linearized and then transformed into Pichia pastoris (P.pastoris) GS115 (His-Mut+) by electroporation. His(+)Mut(+) recombinant strains were identified by PCR and cultivated on MM/MD plates. The influence of different factors on biomass and rSCoVN protein production during induction phase, such as various induction media, dissolved oxygen (DO) and different final concentrations of methanol, was subsequently studied. The expression level and activation were detected by SDS-PAGE and Western-blot respectively. RESULTS All of the recombinants were His(+)Mut(+) after transformation of P.pastoris with linearized plasmids. The BMMY medium was optimal for recombinant ScoVN (rSCoVN) protein expression and growth of the recombinant strains. The final optimal concentration of methanol was 20 mL/L, the DO had a significant effect on rSCoVN protein expression and growth of recombinant strains. The rSCoVN protein expressed in recombinant strains was about 8% of the total cell protein, 520 mg/L of rSCoVN protein was achieved, and a maximum cell A at 600 nm of 62 was achieved in shake flask culture. The rSCoVN protein had a high specificity against mouse-anti-SARS-CoVN-mAb and SARS positive sera, but had no cross-reaction with normal human serum. The biological activity of rSCoVN expressed in P.pastoris was about 4-fold higher than that expressed in E.coli when the same rSCoVN protein quantity was used. CONCLUSION Active recombinant severe acute respiratory syndrome (SARS) coronavirus nucleocapsid (rSCoVN) protein can be successfully expressed in recombinant methylotrophic yeast P.pastoris GS115. The rSCoVN protein has a high specificity against SARS-CoVN-mAb and SARS positive sera, but has no cross-reaction with normal human serum. This provides a basis for further researches on the early diagnosis of SARS and the mechanism of SCoV.


docid: ywqpluvb

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

text: Since late February 2003, CDC has been supporting the World Health Organization (WHO) in the investigation of a multicountry outbreak of atypical pneumonia of unknown etiology. The illness is being referred to as severe acute respiratory syndrome (SARS). This report describes the scope of the outbreak, preliminary case definition, and interim infection control guidance for the United States.


title: Methods of suicide among persons aged 10-19 years--United States, 1992-2001.

text: In 2001, suicide was the third leading cause of death among persons aged 10-19 years. The most common method of suicide in this age group was by firearm (49%), followed by suffocation (mostly hanging) (38%) and poisoning (7%). During 1992-2001, although the overall suicide rate among persons aged 10-19 years declined from 6.2 to 4.6 per 100,000 population, methods of suicide changed substantially. To characterize trends in suicide methods among persons in this age group, CDC analyzed data for persons living in the United States during 1992-2001. This report summarizes the results of that analysis, which indicated a substantial decline in suicides by firearm and an increase in suicides by suffocation in persons aged 10-14 and 15-19 years. Beginning in 1997, among persons aged 10-14 years, suffocation surpassed firearms as the most common suicide method. The decline in firearm suicides combined with the increase in suicides by suffocation suggests that changes have occurred in suicidal behavior among youths during the preceding decade. Public health officials should develop intervention strategies that address the challenges posed by these changes, including programs that integrate monitoring systems, etiologic research, and comprehensive prevention activities.


title: Field isolates of transmissible gastroenteritis virus differ at the molecular level from the Miller and Purdue virulent and attenuated strains and from porcine respiratory coronaviruses.

text: The diversity in selected regions of the transmissible gastroenteritis virus (TGEV) and porcine respiratory coronavirus (PRCV) genomes was analyzed among known TGEV and PRCV strains and field isolates. The N-terminal half of the spike (S) glycoprotein gene and open reading frames (ORF) 3, 3-1 and 4 were amplified by reverse transcriptase reaction and polymerase chain reaction (RT/PCR), and analyzed using restriction fragment length polymorphism (RFLP) patterns of the amplified DNA. Reference TGEV strains (Miller and Purdue) and a PRCV strain (ISU-1), and TGEV and PRCV field isolates were analyzed. Based on the size of the ORF 3, 3-1 and 4 RT/PCR products, TGEV and PRCV strains could be quickly and easily differentiated into three groups designated TGEV Miller, Purdue types and PRCV. By RFLP analysis of the N-terminal region of the S glycoprotein gene and ORFs 3, 3-1 and 4, TGEV and PRCV strains were differentiated into five groups using the restriction enzyme Sau3AI. Sequence analysis of a PCR product in the ORFs 3, 3-1 and 4 from virulent and attenuated Miller strains demonstrated additional differences in that region which have been correlated with a change in virulence of TGEV isolates.


title: An Urgent Call to Make One Health Work for People and Our Planet.

text: January 2020 begins a new decade, a chance for the inter-national health community to take a hard look at where we are, where we stand, what we stand for and why we need to stand up. Staring us down are two concurrent global health emergencies: the coronavirus epidemic originating in Wu-han, China and climate change. As you read this, the trove of articles and assessments published on both is growing faster than most can absorb.


title: Associated inflammatory response in pneumonia: role of adjunctive therapy with glucocorticoids.

text: PURPOSE OF REVIEW This article reviews the potential use of glucocorticoids as adjunctive therapy in the management of patients with severe bacterial pneumonia or pulmonary infections of other etiologies. RECENT FINDINGS The importance of an adequate assessment of the inflammatory process and the appearance of inflammatory markers that correlate with the severity of pneumonia is underlined. A recent randomized clinical trial indicates that adjunctive treatment of severe community-acquired pneumonia with glucocorticoids reduces complications and improves survival. The role of glucocorticoids in other lung infections is also reviewed. The design of new compounds with similar anti-inflammatory properties to classical glucocorticoids but with significantly fewer side effects constitutes a specific challenge for the near future. SUMMARY Although adjunctive treatment with glucocorticoids in severe pneumonia is probably indicated, further randomized clinical trials are urgently needed to confirm the preliminary positive results. In this regard, a proper evaluation of the inflammatory response is likely to be essential for the accurate selection of the target population.


docid: mtndobzn

title: Targeted gap junction protein constructs reveal connexin-specific differences in oligomerization.

text: To define further the mechanisms of gap junction protein (connexin (Cx)) oligomerization without pharmacologic disruption, we have examined the transport and assembly of connexin constructs containing C-terminal di-lysine-based endoplasmic reticulum (ER) (HKKSL) or ER-Golgi intermediate compartment (AKKFF) targeting sequences. By immunofluorescence microscopy, Cx43-HKKSL transiently transfected into HeLa cells showed a predominantly ER localization, although Cx43-AKKFF was localized to the perinuclear region of the cell. Sucrose gradient analysis of Triton X-100-solubilized connexins showed that either Cx43-HKKSL or Cx43-AKKFF expressed alone by HeLa cells was maintained as an apparent monomer. In contrast to Cx43-HKKSL, Cx32-HKKSL was maintained in the ER as stable hexamers, consistent with the notion that Cx32 and Cx43 oligomerization occur in distinct intracellular compartments. Furthermore, Cx43-HKKSL and Cx43-AKKFF inhibited trafficking of Cx43 and Cx46 to the plasma membrane. The inhibitory effect was because of the formation of mixed oligomers between Cx43-HKKSL or Cx43-AKKF and wild type Cx43 or Cx46. Taken together, these results suggest that Cx43-HKKSL and Cx43-AKKFF recirculate through compartments where oligomerization occurs and may be maintained as apparent monomers by a putative Cx43-specific quality control mechanism.


title: Antigenic relationship and further characterization of two major Borna disease virus-specific proteins.

text: After immunization of mice with isolated Borna disease virus (BDV)-specific proteins having Mrs of 38/39K and 24K, monoclonal antibodies (MAbs) were obtained which were specific for one of the antigens in Western blot analysis. However, in immunoprecipitation assays it was found that some MAbs of each specificity reacted exclusively with their respective antigen from BDV-infected cells, whereas other MAbs coprecipitated the heterologous protein. The relationship between the 38/39K and 24K proteins was demonstrated by two-dimensional peptide mapping, which revealed four identical peptides. Additionally, it was found that neither the 38/39K nor the 24K protein is glycosylated, but that the 24K protein is phosphorylated at serine residues. Experiments employing various cell separation protocols revealed that the 38/39K and the 24K proteins are evenly distributed within infected cells; this was confirmed by immunofluorescence techniques using 38/39K- or 24K-specific MAbs. Iodination experiments clearly demonstrated that only the 38/39K protein is expressed on the surface of virus-infected cells.


title: Pattern of diarrhoea in newborn beef calves in south-west France.

text: A prospective study was carried out on 94 randomly selected beef herds in the Midi-Pyrénées region in France. The objective was to describe diarrhoea and mortality in beef calves from birth to 30 days of age. Calves (3,080) were followed from December 1995 to April 1996, and a total of 700 visits allowed records of herd management practices, individual data and environmental conditions to be collected. The incidence rate for diarrhoea during the neonatal period was 14.6%, and varied markedly between herds. Eighteen herds did not suffer from diarrhoea, while five herds had an incidence of more than 50%. Results indicate that 52% of diarrhoea appears during the first week and only 15% after the second week of life. The greatest risk of diarrhoea for a calf was during the first and second weeks of life (7.9 and 6.5 times, respectively). The month of birth was also significantly associated with morbidity, the highest incidence was observed in December and March (17.6 and 23.6%, respectively). Escherichia coli was isolated from 20.3% of faecal samples and appeared earlier during the first days of life. Rotavirus was frequently isolated (47.4%) from samples. Coronavirus was positive for only 16.5% but was significantly associated with diarrhoea. Cryptosporidium was less frequent (15.6%). The global mortality rate was 3.6% and was two-times higher in December than in other months. Forty per cent of herds did not exhibit mortality, and 10% had mortality rates greater than 10%. This study confirms previously reported data, and with greater precision and details on diarrhoea and mortality incidences among herds, age and month of birth in suckling beef calves.


title: Clinical manifestations of two cases with severe acute respiratory syndrome (SARS) in I-Lan County.

text: Severe acute respiratory syndrome (SARS) is a new respiratory tract infectious disease caused by a novel coronavirus. As of this report, there were 3 probable SARS cases in I-Lan County. Of them, 1 was deceased in another hospital and the remaining 2 were cured and discharged. This report describes the clinical manifestations of the 2 surviving probable cases. The first case had a travel history to Guangdong province, China, and the second case probably contracted the disease from a hospital outbreak. They both developed infiltrations over uni- or bilateral lungs but recovered without intubations. Their treatment modalities included empirical antibiotics, steroids, and anti-viral agents. As SARS becomes an emerging infectious disease in the 21st century, its clinical manifestations and treatment will be discussed.


title: Integrated microfluidic systems for sample preparation and detection of respiratory pathogen Bordetella pertussis.

text: An integrated microfluidic system for combined manipulation, pre-concentration, and lysis of samples containing Bordetella pertussis by dielectrophoresis and electroporation has been developed and implemented. The microfluidic device was able to pre-concentrate the amount of B. pertussis cells present in 200 microl of a B. pertussis suspension stock into a 20 microl volume. The device exhibited optimal sample pre-concentration of 6.7x at a stock value of 10(3) cfu/ml and at a flow rate of 250 microl/h. Electro-disruption experiments showed that on-chip-based electroporation is an effective solution for lysis of B. pertussis cells that is easily integrated with dielectrophoresis assisted pre-concentration procedures. Pulsed voltage applied, number of pulses, and presence of potassium chloride in a B. pertussis suspension showed a reduction in B. pertussis cell viability by electroporation; and transmission electron microscopy confirmed B. pertussis cell disruption by electroporation. Genetic amplification and detection of the pre-concentrated sample employing an integrated chip-based system demonstrated a complete chip approach for pathogen detection.


title: Detection of feline coronavirus antibody, feline immunodeficiency virus antibody, and feline leukemia virus antigen in ascites from cats with effusive feline infectious peritonitis.

text: To investigate the usefulness of ascites as a material for viral tests in cats with effusive feline infectious peritonitis (FIP), we attempted to detect anti-feline coronavirus antibody, anti-feline immunodeficiency virus antibody, and feline leukemia virus antigen in ascites from 88 cats clinically suspected with effusive FIP. In each of these three viral tests, all cats positive for serum antibody/antigen were also positive for ascitic antibody/antigen, while cats negative for serum antibody/antigen were also negative for ascitic antibody/antigen. This finding indicates that ascites is useful for these viral tests.


Murine coronavirus 5'-end genomic RNA sequence reveals mechanism of leader-primed transcription.


title: How generation intervals shape the relationship between growth rates and reproductive numbers.

text: Mathematical models of transmission have become invaluable management tools in planning for the control of emerging infectious diseases. A key variable in such models is the reproductive number R. For new emerging infectious diseases, the value of the reproductive number can only be inferred indirectly from the observed exponential epidemic growth rate r. Such inference is ambiguous as several different equations exist that relate the reproductive number to the growth rate, and it is unclear which of these equations might apply to a new infection. Here, we show that these different equations differ only with respect to their assumed shape of the generation interval distribution. Therefore, the shape of the generation interval distribution determines which equation is appropriate for inferring the reproductive number from the observed growth rate. We show that by assuming all generation intervals to be equal to the mean, we obtain an upper bound to the range of possible values that the reproductive number may attain for a given growth rate. Furthermore, we show that by taking the generation interval distribution equal to the observed distribution, it is possible to obtain an empirical estimate of the reproductive number.


title: Identification of a novel cleavage activity of the first papain-like proteinase domain encoded by open reading frame 1a of the coronavirus Avian infectious bronchitis virus and characterization of the cleavage products.

text: The coronavirus Avian infectious bronchitis virus (IBV) employs polyprotein processing as a strategy to express its gene products. Previously we identified the first cleavage event as proteolysis at the Gly(673)-Gly(674) dipeptide bond mediated by the first papain-like proteinase domain (PLPD-1) to release an 87-kDa mature protein. In this report, we demonstrate a novel cleavage activity of PLPD-1. Expression, deletion, and mutagenesis studies showed that the product encoded between nucleotides 2548 and 8865 was further cleaved by PLPD-1 at the Gly(2265)-Gly(2266) dipeptide bond to release an N-terminal 195-kDa and a C-terminal 41-kDa cleavage product. Characterization of the cleavage activity revealed that the proteinase is active on this scissile bond when expressed in vitro in rabbit reticulocyte lysates and can act on the same substrate in trans when expressed in intact cells. Both the N- and C-terminal cleavage products were detected in virus-infected cells and were found to be physically associated. Glycosidase digestion and site-directed mutagenesis studies of the 41-kDa protein demonstrated that it is modified by N-linked glycosylation at the Asn(2313) residue encoded by nucleotides 7465 to 7467. By using a region-specific antiserum raised against the IBV sequence encoded by nucleotides 8865 to 9786, we also demonstrated that a 33-kDa protein, representing the 3C-like proteinase (3CLP), was specifically immunoprecipitated from the virus-infected cells. Site-directed mutagenesis and expression studies showed that a previously predicted cleavage site (Q(2583)-G(2584)) located within the 41-kDa protein-encoding region was not utilized by 3CLP, supporting the conclusion that the 41-kDa protein is a mature viral product.


title: Resource allocation on the frontlines of public health preparedness and response: report of a summit on legal and ethical issues.

text: OBJECTIVES In the face of all-hazards preparedness challenges, local and state health department personnel have to date lacked a discrete set of legally and ethically informed public health principles to guide the distribution of scarce resources in crisis settings. To help address this gap, we convened a Summit of academic and practice experts to develop a set of principles for legally and ethically sound public health resource triage decision-making in emergencies. METHODS The invitation-only Summit, held in Washington, D.C., on June 29, 2006, assembled 20 experts from a combination of academic institutions and nonacademic leadership, policy, and practice settings. The Summit featured a tabletop exercise designed to highlight resource scarcity challenges in a public health infectious disease emergency. This exercise served as a springboard for Summit participants' subsequent identification of 10 public health emergency resource allocation principles through an iterative process. RESULTS The final product of the Summit was a set of 10 principles to guide allocation decisions involving scarce resources in public health emergencies. The principles are grouped into three categories: obligations to community; balancing personal autonomy and community well-being/benefit; and good preparedness practice. CONCLUSIONS The 10 Summit-derived principles represent an attempt to link law, ethics, and real-world public health emergency resource allocation practices, and can serve as a useful starting framework to guide further systematic approaches and future research on addressing public health resource scarcity in an all-hazards context.


title: Severe COVID-19 Cases: Is Respiratory Distress Partially Explained by Central Nervous System Involvement?

text: The main characteristics and challenging symptoms of COVID-19, caused by the novel coronavirus SARS-CoV-2, are related to re-spiratory distress. Although most patients have mild symptoms such as fever, headache, cough, myalgia and anosmia, some develop acute respiratory distress syndrome, leading to death in many cases. Human coronavirus (CoVs) were responsible for two previ-ous worldwide outbreaks: Severe Acute Respiratory Syndrome (SARS-CoV) and Middle East Respiratory Syndrome (MERS-CoV). Several reports of these outbreaks demonstrated that these diseases affected the central nervous system (CNS).[1] Thus, for the current COVID-19 pandemic, a crucial question arises: does CNS affection at least partially explain the respiratory distress commonly found in these patients?


title: Immunogenic peptide comprising a mouse hepatitis virus A59 B-cell epitope and an influenza virus T-cell epitope protects against lethal infection.

text: The coronavirus spike protein S is responsible for important biological activities including virus neutralization by antibody, cell attachment, and cell fusion. Recently, we have elucidated the amino acid sequence of an S determinant common in murine coronaviruses (W. Luytjes, D. Geerts, W. Posthumus, R. Meloen, and W. Spaan, J. Virol. 63:1408-1412, 1989). A monoclonal antibody directed to this determinant (MAb 5B19.2) protected mice against acute fatal infection. In this study, BALB/c mice were immunized with a synthetic peptide of 13 amino acids corresponding to the binding site of MAb 5B19.2, which was either extended with an amino acid sequence of influenza virus hemagglutinin or conjugated to keyhole limpet hemocyanin. Both immunogens induced S-specific antibodies in mice, but only the hemagglutinin-peptide construct protected them against lethal challenge. In contrast to mouse hepatitis virus type 4 (MHV-4), MHV-A59 was not neutralized in vitro by MAb 5B19.2. Neither MHV-A59 nor MHV-4 was neutralized in vitro by antibodies comprising by the synthetic peptides. Our results demonstrated that antibodies elicited with a synthetic peptide comprising a B-cell epitope and a T-helper cell determinant can protect mice against an acute fetal mouse hepatitis virus infection.


title: [Chest X-ray features of severe acute respiratory syndrome and clinical staging].

text: OBJECTIVE To establish a clinical staging system for patients with severe acute respiratory syndrome (SARS) based on clinical feature, laboratory tests as well as dynamic changes of chest X-ray images. METHOD Dynamic changes of chest X-ray images and laboratory tests in 45 SARS patients managed from March to May, 2003 were analyzed. RESULTS (1) Chest X-ray image: among 45 cases, 23 were common type: the time to appearance of unilateral patched shadow of the lung were 2 to 5 (2.9 +/- 1.0) days. The time to appearance of bilateral patched shadow of the lungs were 2 to 12 (6.9 +/- 2.5) days. The time to appearance of ground glass or consolidation in the lung were 6 to 19 (11.0 +/- 2.0) days. The time to the beginning of absorption of X-ray changes were 10 to 21 (15.0 +/- 4.1) days. The time for chest X-ray image to be absorbed completely were 18 to 46 (25.9 +/- 7.2) days. Twenty-two patients were severe type, in which the time to the appearance of ground glass of the lung were (9.0 +/- 3.2) days, with no significant difference when compared with common type (P < 0.05). However, the time to the beginning of absorption and complete absorption were (19.0 +/- 4.6) days (P = 0.009) and (36.0 +/- 8.1) days (P = 0.001), respectively. Noticeably, the time to pan-consolidation of the lung were less than 7 days in 7 fatal cases. (2) Laboratory tests: decrease in the number of lymphocytes and T lymphocyte subset were seen in the early stage. While the account recovered in 10 to 14 days of disease course in the 38 patients who survived, there was no recovery in 7 patients who died. CONCLUSIONS SARS can be divided into five stages: incubation period 2 to 10 days, prodromal period 1 to 3 days, progressive period 4 to 7 days, advanced period 8 to 15 days were, convalescent period 16 to 24 days. The appearance of pan-consolidation in the lung in less than 7 days and/or unable to recover the number of lymphocytes and T lymphocyte subset will be associated with poor prognosis.


title: Leukoencephalomyelopathy in specific pathogen-free cats.

text: Investigations were carried out on 8 specific pathogen-free cats (5 male and 3 female) from a colony experiencing "outbreaks" of progressive hind limb ataxia in 190 of 540 at-risk animals ranging from 3 months to 3 years old. These studies identified moderate to severe bilateral axonal degeneration within white matter regions of the cervical, thoracic, and lumbar spinal cord and in the white matter of the cerebral internal capsule and peduncle, in the roof of the fourth ventricle and inferior cerebellar peduncle, and in the external arcuate and pyramidal fibres of the medulla. There were varying degrees of accompanying microgliosis, astrocytosis, and capillary hyperplasia. Such a clinicopathologic syndrome, termed feline leukoencephalomyelopathy, has previously been described in cat colonies in Britain and New Zealand, although its etiology has not been determined. The degenerative nature of the lesions and their bilateral distribution suggest possible nutritional, metabolic, or toxic causes. Although these findings provide circumstantial evidence that the exclusive feeding of a gamma-irradiated diet of reduced vitamin A content is associated with the development of the neuronal lesions, further tissue micronutrient and antioxidant analysis will be required to support this hypothesis.


MHV subgenomic negative strand function.


title: Monoclonal antibody-mediated enhancement of dengue virus infection in vitro and in vivo and strategies for prevention.

text: Infection with dengue virus (DENV) or any other flavivirus induces cross-reactive, but weakly neutralizing or nonneutralizing, antibodies that recognize epitopes involving the fusion peptide in the envelope glycoprotein. Humanized mAb IgG 1A5, derived from a chimpanzee, shares properties of cross-reactive antibodies. mAb IgG 1A5 up-regulated DENV infection by a mechanism of antibody-dependent enhancement (ADE) in a variety of Fc receptor-bearing cells in vitro. A 10- to 1,000-fold increase of viral yield in K562 cells, dependent on the DENV serotype, was observed over a range of subneutralizing concentrations of IgG 1A5. A significant increase of DENV-4 viremia titers (up to 100-fold) was also demonstrated in juvenile rhesus monkeys immunized with passively transferred dilutions of IgG 1A5. These results, together with earlier findings of ADE of DENV-2 infection by a polyclonal serum, establish the primate model for analysis of ADE. Considering the abundance of these cross-reactive antibodies, our observations confirm that significant viral amplification could occur during DENV infections in humans with prior infection or with maternally transferred immunity, possibly leading to severe dengue. Strategies to eliminate ADE were explored by altering the antibody Fc structures responsible for binding to Fc receptors. IgG 1A5 variants, containing amino acid substitutions from the Fc region of IgG2 or IgG4 antibodies, reduced but did not eliminate DENV-4-enhancing activity in K562 cells. Importantly, a 9-aa deletion at the N terminus of the CH(2) domain in the Fc region abrogated the enhancing activity.


title: Will your ED have staff quarantined for SARS? Brace yourself for the worst.

text: One Albuquerque, NM, ED's staff were quarantined after exposure to a suspected severe acute respiratory syndrome (SARS) patient, which underscores the importance of reducing risks of transmission. Reduce the number of contacts by isolating patients immediately. Triage nurses should have quick access to N-95 respirators. Ask security to screen all patients arriving by car before they enter the ED.


Understanding immune effects of oestrogens to explain the reduced morbidity and mortality in female versus male COVID-19 patients. Comparisons with autoimmunity and vaccination.


title: Lack of an effect of a commercial vaccine adjuvant on the development of postweaning multisystemic wasting syndrome (PMWS) in porcine circovirus type 2 (PCV2) experimentally infected conventional pigs.

text: The objective of this study was to evaluate the effect of a commercial vaccine adjuvant on the clinical and pathological outcome of PCV2 experimentally infected 8 to 9-week-old conventional pigs. Forty-four pigs were divided into four groups: non-infected control pigs, pigs that received a vaccine adjuvant, pigs inoculated with PCV2, and pigs inoculated with PCV2 together with the vaccine adjuvant. Infection was monitored until 69 days post-inoculation (PI). Some PCV2 inoculated pigs had hyperthermia, but no other clinical signs were recorded. No characteristic PMWS gross or microscopic lesions were observed in any of the pigs. PCV2 DNA was detected in lymphoid tissues by in situ hybridisation in 6 PCV2 inoculated pigs on day 69 PI. All PCV2 inoculated pigs seroconverted between days 21 and 49 PI, shortly after viremia detection. Moreover, viremia was detected between days 7 and 69 PI using PCR. A peak of the virus load was detected by real-time quantitative PCR between days 14 and 21 PI. There were no significant differences in the proportion of PCV2 positive serum and in the viral load between PCV2 and PCV2 + adjuvant inoculated pigs. Although PMWS was not reproduced in neither PCV2 nor PCV2 + adjuvant inoculated pigs, viremia detection and seroconversion indicated that all PCV2 inoculated pigs developed a chronic long-term asymptomatic infection. An increase of PCV2 replication was not observed in pigs inoculated with the adjuvant. These results indicate that the principle of immunostimulation may not be applicable under the experimental conditions used, suggesting that not all adjuvants used in commercial vaccines are capable of triggering mechanisms for PMWS development.


title: Lung cancer: developmental networks gone awry?

text: High-throughput genomic data for both lung development and lung cancer continue to accumulate. Significant molecular intersection between these two processes has been hypothesized due to overlap in phenotypes and genomic variation. Examining the network biology of both cancer and development of the lung may shed functional light on the individual signaling modules involved. Stem cell biology may explain a portion of this network intersection and consequently studying lung organogenesis may have relevance for understanding lung cancer. This review summarizes our understanding of the potential overlapping mechanisms involved in lung development and lung tumorigenesis.