title: Intrinsic disorder in the Protein Data Bank.

text: The Protein Data Bank (PDB) is the preeminent source of protein structural information. PDB contains over 32,500 experimentally determined 3-D structures solved using X-ray crystallography or nuclear magnetic resonance spectroscopy. Intrinsically disordered regions fail to form a fixed 3-D structure under physiological conditions. In this study, we compare the amino-acid sequences of proteins whose structures are determined by X-ray crystallography with the corresponding sequences from the Swiss-Prot database. The analyzed dataset includes 16,370 structures, which represent 18,101 PDB chains and 5,434 different proteins from 910 different organisms (2,793 eukaryotic, 2,109 bacterial, 288 viral, and 244 archaeal). In this dataset, on average, each Swiss-Prot protein is represented by 7 PDB chains with 76% of the crystallized regions being represented by more than one structure. Intriguingly, the complete sequences of only approximately 7% of proteins are observed in the corresponding PDB structures, and only approximately 25% of the total dataset have >95% of their lengths observed in the corresponding PDB structures. This suggests that the vast majority of PDB proteins is shorter than their corresponding Swiss-Prot sequences and/or contain numerous residues, which are not observed in maps of electron density. To determine the prevalence of disordered regions in PDB, the residues in the Swiss-Prot sequences were grouped into four general categories, "Observed" (which correspond to structured regions), "Not observed" (regions with missing electron density, potentially disordered), "Uncharacterized," and "Ambiguous," depending on their appearance in the corresponding PDB entries. This non-redundant set of residues can be viewed as a 'fragment' or empirical domain database that contains a set of experimentally determined structured regions or domains and a set of experimentally verified disordered regions or domains. We studied the propensities and properties of residues in these four categories and analyzed their relations to the predictions of disorder using several algorithms. "Non-observed," "Ambiguous," and "Uncharacterized" regions were shown to possess the amino acid compositional biases typical of intrinsically disordered proteins. The application of four different disorder predictors (PONDR(R) VL-XT, VL3-BA, VSL1P, and IUPred) revealed that the vast majority of residues in the "Observed" dataset are ordered, and that the "Not observed" regions are mostly disordered. The "Uncharacterized" regions possess some tendency toward order, whereas the predictions for the short "Ambiguous" regions are really ambiguous. Long "Ambiguous" regions (>70 amino acid residues) are mostly predicted to be ordered, suggesting that they are likely to be "wobbly" domains. Overall, we showed that completely ordered proteins are not highly abundant in PDB and many PDB sequences have disordered regions. In fact, in the analyzed dataset approximately 10% of the PDB proteins contain regions of consecutive missing or ambiguous residues longer than 30 amino-acids and approximately 40% of the proteins possess short regions (> or =10 and < 30 amino-acid long) of missing and ambiguous residues.


title: Specific serology for emerging human coronaviruses by protein microarray.

text: We present a serological assay for the specific detection of IgM and IgG antibodies against the emerging human coronavirus hCoV-EMC and the SARS-CoV based on protein microarray technology. The assay uses the S1 receptor-binding subunit of the spike protein of hCoV-EMC and SARS-CoV as antigens. The assay has been validated extensively using putative cross-reacting sera of patient cohorts exposed to the four common hCoVs and sera from convalescent patients infected with hCoV-EMC or SARS-CoV.


title: Respiratory tract viral infections in inner-city asthmatic adults.

text: BACKGROUND Respiratory tract viral infections (RTVIs) have been identified frequently in association with asthma exacerbations in children, but few studies have shown similar rates of viral infections in adults with asthma. Further studies using newer diagnostic techniques to evaluate the frequency of RTVIs in adults with acute exacerbations of asthma need to be performed. METHODS Twenty-nine asthmatic adults were recruited from the pulmonary clinic of an urban county hospital and were followed up in a longitudinal cohort study for signs and symptoms of asthma and RTVI. One hundred twenty-two asthmatic adults presenting to the emergency department (ED) of the same hospital with acute symptoms of asthma underwent evaluation for RTVI in a cross-sectional prevalence study. In both studies, respiratory secretions and paired serum samples were collected from subjects with acute wheezing episodes and evaluated using virus culture, serologic testing, and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS In the longitudinal cohort study, 138 respiratory illnesses, of which 87 were asthma exacerbations, were evaluated; 41% of all illnesses and 44% of asthma exacerbations were associated with an RTVI. In the ED study, 148 asthma exacerbations were evaluated; 55% were associated with an RTVI. An RTVI was identified in 21 (50%) of 42 of the subjects hospitalized in the ED study. Picornaviruses (rhinoviruses), coronaviruses, and influenza viruses were the most commonly identified causes of RTVI. Forty-six (60%) of the 77 picornavirus infections and 22 (71%) of the 31 coronavirus infections were identified only using RT-PCR. CONCLUSIONS Asthmatic exacerbations in adults are frequently associated with an RTVI. Identification of such infections often requires newer diagnostic methods, such as virus-specific RT-PCR. The high frequency of RTVIs identified in association with asthmatic exacerbations in adults from the inner city suggests that strategies for the prevention of RTVI should be targeted toward this population.


title: [Evaluation of the safety of innovative drugs against viruses and infectious agents].

text: Recently, several novel cellular therapy products and biological drugs are being developed to treat various previously untreatable diseases. One of the most important issues regarding these innovations is how to ensure safety over infectious agents, including viruses and prions, in the earliest treatments with these products. The object of this study is a risk assessment of cases of human infectious with the agents and to present a sample risk management plan based on a collaboration among the National Institute of Health Sciences, universities, marketing authorization holders, and scientific societies. There are three subjects of study: (1) the viral safety of cellular therapy products, (2) the viral safety of biological drugs, and (3) the safety of prions. In this report, we describe the objects of the study, the project members, the study plan outline, and the ongoing plans. The results of the viral risk identification and the risk analysis of cellular therapy products will also be described, based on a review of the literature and case reports obtained during the first year of this project.


title: Health effects of subchronic exposure to environmental levels of diesel exhaust.

text: Diesel exhaust is a public health concern and contributor to both ambient and occupational air pollution. As part of a general health assessment of multiple anthropogenic source emissions conducted by the National Environmental Respiratory Center (NERC), a series of health assays was conducted on rats and mice exposed to environmentally relevant levels of diesel exhaust. This article summarizes the study design and exposures, and reports findings on several general indicators of toxicity and carcinogenic potential. Diesel exhaust was generated from a commonly used 2000 model 5.9-L, 6-cylinder turbo diesel engine operated on a variable-load heavy-duty test cycle burning national average certification fuel. Animals were exposed to clean air (control) or four dilutions of whole emissions based on particulate matter concentration (30, 100, 300, and 1000 microg/m(3)). Male and female F344 rats and A/J mice were exposed by whole-body inhalation 6 h/day, 7 days/wk, for either 1 wk or 6 mo. Exposures were characterized in detail. Effects of exposure on clinical observations, body and organ weights, serum chemistry, hematology, histopathology, bronchoalveolar lavage, and serum clotting factors were mild. Significant exposure-related effects occurring in both male and female rats included decreases in serum cholesterol and clotting Factor VII and slight increases in serum gamma-glutamyl transferase. Several other responses met screening criteria for significant exposure effects but were not consistent between genders or exposure times and were not corroborated by related parameters. Carcinogenic potential as determined by micronucleated reticulocyte counts and proliferation of adenomas in A/J mice were unaffected by 6 mo of exposure. Parallel studies demonstrated effects on cardiac function and resistance to viral infection; however, the results reported here show few and only modest health hazards from subchronic or shorter exposures to realistic concentrations of contemporary diesel emissions.


title: T-cell epitopes in severe acute respiratory syndrome (SARS) coronavirus spike protein elicit a specific T-cell immune response in patients who recover from SARS.

text: The immunogenicity of HLA-A2-restricted T-cell epitopes in the S protein of the Severe acute respiratory syndrome coronavirus (SARS-CoV) and of human coronavirus strain 229e (HCoV-229e) was analyzed for the elicitation of a T-cell immune response in donors who had fully recovered from SARS-CoV infection. We employed online database analysis to compare the differences in the amino acid sequences of the homologous T epitopes of HCoV-229e and SARS-CoV. The identified T-cell epitope peptides were synthesized, and their binding affinities for HLA-A2 were validated and compared in the T2 cell system. The immunogenicity of all these peptides was assessed by using T cells obtained from donors who had fully recovered from SARS-CoV infection and from healthy donors with no history of SARS-CoV infection. HLA-A2 typing by indirect immunofluorescent antibody staining showed that 51.6% of SARS-CoV-infected patients were HLA-A2 positive. Online database analysis and the T2 cell binding test disclosed that the number of HLA-A2-restricted immunogenic epitopes of the S protein of SARS-CoV was decreased or even lost in comparison with the homologous sequences of the S protein of HCoV-229e. Among the peptides used in the study, the affinity of peptides from HCoV-229e (H77 and H881) and peptides from SARS-CoV (S978 and S1203) for binding to HLA-A2 was higher than that of other sequences. The gamma interferon (IFN-gamma) release Elispot assay revealed that only SARS-CoV-specific peptides S1203 and S978 induced a high frequency of IFN-gamma-secreting T-cell response in HLA-A2(+) donors who had fully recovered from SARS-CoV infection; such a T-cell epitope-specific response was not observed in HLA-A2(+) healthy donors or in HLA-A2(-) donors who had been infected with SARS-CoV after full recovery. Thus, T-cell epitopes S1203 and S978 are immunogenic and elicit an overt specific T-cell response in HLA-A2(+) SARS-CoV-infected patients.


title: The efficacy and safety of the "hybrid" approach to coronary chronic total occlusions: insights from a contemporary multicenter US registry and comparison with prior studies.

text: BACKGROUND Percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) is challenging and has been associated with low success rates. However, recent advancements in equipment and the flexibility to switch between multiple technical approaches during the same procedure ("hybrid" percutaneous algorithm) have dramatically increased the success of CTO-PCI. We sought to compare the contemporary procedural outcomes of hybrid CTO-PCI with previously published CTO-PCI studies. METHODS The procedural outcomes of 497 consecutive CTO-PCIs performed between January 2012 and August 2013 at five high-volume centers in the United States were compared with the pooled success and complication rates reported in 39 prior CTO-PCI series that included ≥100 patients and were published after 2000. RESULTS The baseline clinical and angiographic characteristics of the study patients were comparable to those of previous studies. Technical and procedural success was achieved in 455 cases (91.5%) and 451 cases (90.7%), respectively, and were significantly higher than the pooled technical and procedural success rates from prior studies (76.5%, P<.001 and 75.2%, P<.001, respectively). Major procedural complications occurred in 9/497 patients (1.8%) overall and included death (2 patients), acute myocardial infarction (5 patients), repeat target vessel PCI (1 patient), and tamponade requiring pericardiocentesis (2 patients). The incidence of major complications was similar to that of prior studies (pooled rate 2.0%; P=.72). CONCLUSION Use of the hybrid approach to CTO-PCI is associated with higher success and similar complication rates compared to prior studies, supporting its expanded use for treating these challenging lesions.


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title: Lessons from outbreaks of H1N1 influenza.

text: A new H1N1 triple-reassortant "swine" influenza virus was recently described in individuals from the United States and Mexico who presented with respiratory symptoms, and the same virus was subsequently confirmed in patients from several countries around the world. The circumstances surrounding the emergence of this pathogen, and the factors that facilitated the initial cross-species transmission, are still incompletely understood. It became apparent in the early days of the outbreak that the virus can be directly transmitted between humans. Pathogens that originate in animal reservoirs and subsequently acquire the potential for human-to-human transmission have caused outbreaks throughout human history. Although each outbreak is marked by its own particularities, it is important to remember the teachings that emerge from previous epidemics and pandemics. Integrating the important lessons of the past will provide the best opportunity to understand host-pathogen interaction and the most powerful approach to implementing effective prophylactic and therapeutic measures.


title: Qualitative analysis of the perception and acceptability of pathogen transport among housewives using focus group interviews.

text: We conducted focus group interviews to understand how residents of Japan feel about the transport of pathogens. Twelve randomly selected housewives, who had no special knowledge regarding the topic before the interview, expressed their opinions in 2 separate meetings regarding pathogen transport. The results of the interviews were analyzed by the KJ method. The analysis found that although the transport of pathogens is universally recognized to be necessary, there is not clear consensus on the exact methods of transport, the positive and/or negative value of such information, and how clearly and/or uniquely to label containers, packages, compartments, vehicles, and conditions used for such transportation. Further studies to improve the skills of both the providers and receivers of such information (a technique of risk communication) are necessary.


title: SARS outbreak in Germany 2003: workload of local health departments and their compliance in quarantine measures--implications for outbreak modeling and surge capacity?

text: OBJECTIVE Public health management of severe acute respiratory syndrome epidemic must be evaluated to improve contingency planning for epidemics. METHODS Standardized questionnaires on case management were sent to local health departments of 15 of 16 states in Germany. RESULTS Of the 384 local health departments who received the questionnaire, 280 (72%) completed them. They reported 271 suspect or probable severe acute respiratory syndrome cases under investigation (average 4.7). The average duration of quarantine was 5.4 days. Contacts without professional activity were 2.78 times more likely to stay under 10-day quarantine than those with professional activity (CI: 0.80-9.86). Local health departments with at least one case under investigation had invested an average of 104.5 working hours. CONCLUSIONS Our contact-case ratios may serve for planning for modeling in epidemics. We found discrepancies between local and national surveillance figures; home quarantine was frequently not applied as recommended and the burden on urban health departments was disproportionally higher. Flexibility of the national surveillance system and surge capacity for the prevention of future epidemics need improvement, particularly in urban health departments.


title: Life events and clinical subtypes of major depression: a cross-sectional study.

text: The present study aimed to investigate the relationship between stressful life events and depression. Ninety major depressive patients, aged 36.57 +/- 12.02 years, and 121 matched controls, aged 27.11 +/- 10.59 years, took part in the study. The life change units (LCU) according to Rahe et al. were used for the quantification of life events. The results suggested that males reported significantly more life events than females. Atypical males differed from all other gender-by-type groups, while no other differences emerged. LCU correlated with melancholic indices but did not correlate with anxiety or functioning. The results suggest that subgroups of depressive patients are characterized by the presence of stressful life events. Male atypical patients reported the highest load of life events. The question that arises is whether this finding is valid or whether these patients (who have higher personality psychopathology and interpersonal rejection sensitivity) tend to over-report life events.


Age and transmissible spongiform encephalopathies.


title: Impact of an outbreak of severe acute respiratory syndrome on a hospital in Taiwan, ROC.

text: STUDY OBJECTIVE To estimate the impact of the severe acute respiratory syndrome (SARS) outbreak in early 2003 on a tertiary care hospital in Taiwan, ROC. METHODS The study estimated the utilisation of resources related to infection control, SARS related medical services, and routine medical services, and SARS related medical outcomes at National Cheng Kung University Hospital (NCKUH) from 25 March to 16 June 2003 through a cross sectional survey of hospital records. RESULTS A mean of 5100 persons per day (95%CI 4580 to 5610) underwent fever screening at the outpatient and emergency department (ED) entrances to the hospital, of which 35 per day (95% CI 30 to 40) were referred for further evaluation for suspected or probable SARS. ED isolation surge capacity was created via 12 new beds outside the ED: eight for SARS assessment, three for patients awaiting in hospital bed assignment, and one for resuscitation. A total of 382 patients were fully evaluated for suspected or probable SARS outside the ED, of which 27 were admitted. The mean numbers of outpatient clinic patient visits, ED visits, ED trauma patient visits, ED admissions, hospital admissions, and operative procedures decreased during the outbreak. Thirty eight patients were hospitalised with suspected SARS, of which three received the final diagnosis of probable SARS. Two patients with probable SARS died. No cases of nosocomial SARS transmission occurred. CONCLUSIONS This SARS outbreak was associated with substantial use of hospital and ED resources aimed at infection control, comparatively less use of resources related to the medical care of patients with suspected or probable SARS, and decreased use of routine medical services.


title: Near-cognate peptidyl-tRNAs promote +1 programmed translational frameshifting in yeast.

text: Translational frameshifting is a ubiquitous, if rare, form of alternative decoding in which ribosomes spontaneously shift reading frames during translation elongation. In studying +1 frameshifting in Ty retrotransposons of the yeast S. cerevisiae, we previously showed that unusual P site tRNAs induce frameshifting. The frameshift-inducing tRNAs we show here are near-cognates for the P site codon. Their abnormal decoding induces frameshifting in either of two ways: weak codon-anticodon pairing allows the tRNA to disengage from the mRNA and slip +1, or an unusual codon-anticodon structure interferes with cognate in-frame decoding allowing out-of-frame decoding in the A site. We draw parallels between this mechanism and a proposed mechanism of frameshift suppression by mutant tRNAs.


Genomic medicine: the future is now. Lessons for Hong Kong from the House of Lords Report on Genomic Medicine.


Coronavirus and multiple sclerosis: results of a case/control longitudinal serological study.


title: Canine and feline parvoviruses can use human or feline transferrin receptors to bind, enter, and infect cells.

text: Canine parvovirus (CPV) enters and infects cells by a dynamin-dependent, clathrin-mediated endocytic pathway, and viral capsids colocalize with transferrin in perinuclear vesicles of cells shortly after entry (J. S. L. Parker and C. R. Parrish, J. Virol. 74:1919-1930, 2000). Here we report that CPV and feline panleukopenia virus (FPV), a closely related parvovirus, bind to the human and feline transferrin receptors (TfRs) and use these receptors to enter and infect cells. Capsids did not detectably bind or enter quail QT35 cells or a Chinese hamster ovary (CHO) cell-derived cell line that lacks any TfR (TRVb cells). However, capsids bound and were endocytosed into QT35 cells and CHO-derived TRVb-1 cells that expressed the human TfR. TRVb-1 cells or TRVb cells transiently expressing the feline TfR were susceptible to infection by CPV and FPV, but the parental TRVb cells were not. We screened a panel of feline-mouse hybrid cells for susceptibility to FPV infection and found that only those cells that possessed feline chromosome C2 were susceptible. The feline TfR gene (TRFC) also mapped to feline chromosome C2. These data indicate that cell susceptibility for these viruses is determined by the TfR.


Management of bronchiolitis.


The discovery of HIV as the cause of AIDS.


title: Development of a method for bacteria and virus recovery from heating, ventilation, and air conditioning (HVAC) filters.

text: The aim of the work presented here is to study the effectiveness of building air handling units (AHUs) in serving as high volume sampling devices for airborne bacteria and viruses. An HVAC test facility constructed according to ASHRAE Standard 52.2-1999 was used for the controlled loading of HVAC filter media with aerosolized bacteria and virus. Nonpathogenic Bacillus subtilis var. niger was chosen as a surrogate for Bacillus anthracis. Three animal viruses; transmissible gastroenteritis virus (TGEV), avian pneumovirus (APV), and fowlpox virus were chosen as surrogates for three human viruses; SARS coronavirus, respiratory syncytial virus, and smallpox virus; respectively. These bacteria and viruses were nebulized in separate tests and injected into the test duct of the test facility upstream of a MERV 14 filter. SKC Biosamplers upstream and downstream of the test filter served as reference samplers. The collection efficiency of the filter media was calculated to be 96.5 +/- 1.5% for B. subtilis, however no collection efficiency was measured for the viruses as no live virus was ever recovered from the downstream samplers. Filter samples were cut from the test filter and eluted by hand-shaking. An extraction efficiency of 105 +/- 19% was calculated for B. subtilis. The viruses were extracted at much lower efficiencies (0.7-20%). Our results indicate that the airborne concentration of spore-forming bacteria in building AHUs may be determined by analyzing the material collected on HVAC filter media, however culture-based analytical techniques are impractical for virus recovery. Molecular-based identification techniques such as PCR could be used.


title: Don't be scared, be angry: the politics and ethics of Ebola.

text: The current outbreak of Ebola virus disease in West Africa is the worst so far. The unprecedented extent of mortality and morbidity in this outbreak has followed more from imposition of neoliberal economic policies on the countries affected than from the biological virulence of Ebola virus. The lack of vaccines and medications for Ebola virus disease is evidence that markets cannot reliably supply treatments for epidemic diseases. We attribute the current difficulties in containment chiefly to the erosion or non-development of the health and medical infrastructure needed to respond effectively, as a direct result of market-privileging policies imposed in the interests of wealthy nations. These events and responses hold lessons for public health priorities in Australia.


title: Heptad repeat 2-based peptides inhibit avian sarcoma and leukosis virus subgroup a infection and identify a fusion intermediate.

text: Fusion proteins of enveloped viruses categorized as class I are typified by two distinct heptad repeat domains within the transmembrane subunit. These repeats are important structural elements that assemble into the six-helix bundles characteristic of the fusion-activated envelope trimer. Peptides derived from these domains can be potent and specific inhibitors of membrane fusion and virus infection. To facilitate our understanding of retroviral entry, peptides corresponding to the two heptad repeat domains of the avian sarcoma and leukosis virus subgroup A (ASLV-A) TM subunit of the envelope protein were characterized. Two peptides corresponding to the C-terminal heptad repeat (HR2), offset from one another by three residues, were effective inhibitors of infection, while two overlapping peptides derived from the N-terminal heptad repeat (HR1) were not. Analysis of envelope mutants containing substitutions within the HR1 domain revealed that a single amino acid change, L62A, significantly reduced sensitivity to peptide inhibition. Virus bound to cells at 4 degrees C became sensitive to peptide within the first 5 min of elevating the temperature to 37 degrees C and lost sensitivity to peptide after 15 to 30 min, consistent with a transient intermediate in which the peptide binding site is exposed. In cell-cell fusion experiments, peptide inhibitor sensitivity occurred prior to a fusion-enhancing low-pH pulse. Soluble receptor for ASLV-A induces a lipophilic character in the envelope which can be measured by stable liposome binding, and this activation was found to be unaffected by inhibitory HR2 peptide. Finally, receptor-triggered conformational changes in the TM subunit were also found to be unaffected by inhibitory peptide. These changes are marked by a dramatic shift in mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, from a subunit of 37 kDa to a complex of about 80 kDa. Biotinylated HR2 peptide bound specifically to the 80-kDa complex, demonstrating a surprisingly stable envelope conformation in which the HR2 binding site is exposed. These experiments support a model in which receptor interaction promotes formation of an envelope conformation in which the TM subunit is stably associated with its target membrane and is able to bind a C-terminal peptide.


title: Impact of enforcing the Labour Ordinance, with 1-in-7-day off for hospital doctors, on weekend hospital discharge rate.

text: BACKGROUND After enforcing the Labour Ordinance, hospital doctors must have 1 day off-work every week. In this study, we aimed to evaluate its impact on the discharge pattern from an acute medical hospital. METHODS We undertook a hospital-based ecologic study with before-after design using the clinical management database of patient discharge records of all acute medical wards in a hospital from January to March 2002 (1 year before new system) and from January to March 2004 (1 year after restricted weekend service). The main outcome measures were the daily discharge rates for the two periods. The odds of being discharged on a Saturday were estimated by multivariate analyses. RESULTS The number of patient discharge on a Saturday was substantially lower in 2004 as compared to 2002 (47.5 +/- 8.5 per Saturday versus 70.5 +/- 11.1 per Saturday, respectively, p < 0.001). A statistically significant decreased trend was noted in the weekend discharge rate in 2002 and 2004 (Poisson p-value for change in discharge rate, p < 0.001). On the other hand, the number of patient discharges on weekdays did not differ between the two periods. Consistently fewer patients were being discharged on Sundays and Mondays as compared to the rest of the week days in both periods. Compared with study period 2002, patients hospitalized in 2004 (with limited weekend service) had significantly lower multivariate-adjusted odds of being discharged on a Saturday (odds ratio of 0.70; 95 percent confidence interval 0.72-0.89, p < 0.0001). CONCLUSIONS Length of hospital stay is influenced by the health care system delivery apart from clinical factors. Restricted weekend services in an acute medical hospital setting substantially lengthen the hospital stay, and might therefore entail a major financial burden.


title: Effect of regular exercise on health and disease.

text: It is known for a long time that exercise increases physical adequacy, has beneficial effects on the general health condition as well as a playing preventing role against various disease states. To decrease the risk of disease and maintain good health, the natural defense system of the organism needs to be strengthened. It is thought that in addition to increasing the body's resistance to disease through the strengthening of the immune system, decreases the convalescence time, increases work efficiency and improves the sportive performance of the individual all which would contribute positively to the national economy. The positive effects of regular exercising of aerobic nature such as strengthening of the immune system, protection against diseases as well as its positive effects on quality of life will help to emphasize the importance of physical exercise and improve the general view of sports by society.


title: Viral aetiology of enzootic pneumonia in Danish dairy herds: diagnostic tools and epidemiology.

text: Ten outbreaks of calf respiratory disease in Danish dairy herds were investigated by lung lavage, and in eight of the herds paired blood samples were tested serologically. In six of the 10 herds bovine respiratory syncytial virus (BRSV) antigen was detected in the lung lavage fluids. In only one calf was coronavirus and BRSV detected simultaneously. The paired blood samples confirmed that four of the herds were BRSV-infected, and in one herd the BRSV infection was diagnosed by the paired blood samples alone. Significant increases in antibody titres against coronavirus were observed in two herds, both in combination with other virological agents. No adenovirus antigen was detected in any of the lavage samples, but in two herds a significant increase in antibody titres against adenovirus was observed. Parainfluenza-3 (PI-3) virus was not detected in the lung lavage fluids, and in four of the herds, no antibodies to PI-3 were detected. In three herds no viral involvement could be found. The findings suggest that BRSV may be an important causative agent in calf respiratory disease in Denmark, even in very young calves.


title: Von Willebrand gene tracking by single-tube automated fluorescent analysis of four short tandem repeat polymorphisms.

text: Molecular diagnosis of von Willebrand disease (VWD) has been hampered by the large size and complex genomic characteristics of the gene involved. For this reason, indirect methods using intragenic polymorphic markers described along the von Willebrand factor (VWF) gene are valuable tools for gene monitoring and linkage analysis. Several studies have demonstrated the four commonly utilized short tandem repeats (STRs), three located in intron 40 and one in the promoter region of the VWF gene, to be highly informative for this task. Our objective was t o develop a rapid, automated method to simultaneously analyze these four STRs for VWF gene tracking. Amplification of the four loci is achieved in a single multiplex fluorescent PCR which is then analyzed in the same run by capillary electrophoresis. Data processing with GeneScan and Genotyper software has simplified management and tabulation of the resulting haplotypes. Analysis of the VWF gene in DNA from 102 individuals (204 chromosomes) revealed that the three STRs within intron 40 showed significant linkage disequilibrium against each other but not against the VWP locus. Moreover, the combination of the four markers offers a high heterozygosity rate (>99%) that improves tracing VWF gene inheritance. In conclusion, the automated fluorescent capillary electrophoresis method presented here is an extremely rapid, simple and highly informative technique for association studies between VWD and the VWF gene in addition to genetic counseling and prenatal diagnosis by precise linkage analysis in VWD-affected families.


title: Beyond the physician charter: reflections on medical professionalism.

text: The numerous challenges now facing the profession of medicine have led to an intense focus on professionalism by individual physicians and by their professional and academic organizations. In 2002, a distinguished group of leaders in internal medicine created the Physician Charter, which calls on physicians to reaffirm medical professionalism through commitment to three principles and 10 responsibilities. The Charter reflects a duty-based ethic that is chiefly concerned with physician competence. This article offers a critical analysis of the Physician Charter from the perspective of the traditional values of medicine as articulated in medical oaths and championed by leaders of past generations, exemplified by William Osler. The authors argue that medical professionalism should reflect the values of a virtue-based ethic that stresses compassion and beneficence, rather than the values of a duty-based ethic. The challenges that now confront the practice of medicine can be addressed successfully only to the extent that physicians promote virtue-ethics, act collectively in the public interest, and render service that clearly transcends their own self-interests.


title: Disseminated histoplasmosis in a Bengal tiger (Panthera tigris).

text: Disseminated infection with Histoplasma capsulatum was diagnosed in a 7-yr-old female Bengal tiger (Panthera tigris). Clinical signs were nonspecific with the exception of brief periods of tachypnea for 5 days prior to death. H. capsulatum organisms were found in the lungs, tracheobronchial lymph nodes, and liver. Diagnosis was confirmed by tracheal wash, urine H. capsulatum enzyme immunoassay, and necropsy results. This report represents the first published account of disseminated histoplasmosis in a tiger.


title: Identification of two critical amino acid residues of the severe acute respiratory syndrome coronavirus spike protein for its variation in zoonotic tropism transition via a double substitution strategy.

text: Severe acute respiratory syndrome coronavirus (SARS-CoV) is a recently identified human coronavirus. The extremely high homology of the viral genomic sequences between the viruses isolated from human (huSARS-CoV) and those of palm civet origin (pcSARS-CoV) suggested possible palm civet-to-human transmission. Genetic analysis revealed that the spike (S) protein of pcSARS-CoV and huSARS-CoV was subjected to the strongest positive selection pressure during transmission, and there were six amino acid residues within the receptor-binding domain of the S protein being potentially important for SARS progression and tropism. Using the single-round infection assay, we found that a two-amino acid substitution (N479K/T487S) of a huSARS-CoV for those of pcSARS-CoV almost abolished its infection of human cells expressing the SARS-CoV receptor ACE2 but no effect upon the infection of mouse ACE2 cells. Although single substitution of these two residues had no effects on the infectivity of huSARS-CoV, these recombinant S proteins bound to human ACE2 with different levels of reduced affinity, and the two-amino acid-substituted S protein showed extremely low affinity. On the contrary, substitution of these two amino acid residues of pcSARS-CoV for those of huSRAS-CoV made pcSARS-CoV capable of infecting human ACE2-expressing cells. These results suggest that amino acid residues at position 479 and 487 of the S protein are important determinants for SARS-CoV tropism and animal-to-human transmission.


title: Development of a red-shifted fluorescence-based assay for SARS-coronavirus 3CL protease: identification of a novel class of anti-SARS agents from the tropical marine sponge Axinella corrugata.

text: SARS-coronavirus (SARS-CoV) encodes a main protease, 3CLpro, which plays an essential role in the viral life cycle and is currently the prime target for discovering new anti-coronavirus agents. In this article, we report our success in developing a novel red-shifted (RS) fluorescence-based assay for 3CLpro and its application for identifying small-molecule anti-SARS agents from marine organisms. We have synthesised and characterised the first generation of a red-shifted internally quenched fluorogenic substrate (RS-IQFS) for 3CLpro based on resonance energy transfer between the donor and acceptor pair CAL Fluor Red 610 and Black Hole Quencher-1 (Km and kcat values of 14 microM and 0.65 min-1). The RS-IQFS primary sequence was selected based on the results of our screening analysis of 3CLpro performed using a series of blue-shifted (BS)-IQFSs corresponding to the 3CLpro-mediated cleavage junctions of the SARS-CoV polyproteins. In contrast to BS-IQFSs, the RS-IQFS was not susceptible to fluorescence interference from coloured samples and allowed for successful screening of marine natural products and identification of a coumarin derivative, esculetin-4-carboxylic acid ethyl ester, a novel 3CLpro inhibitor (IC50=46 microM) and anti-SARS agent (EC50=112 microM; median toxic concentration>800 microM) from the tropical marine sponge Axinella corrugata.


title: The proportion of specific viral subpopulations in attenuated Arkansas Delmarva poultry industry infectious bronchitis vaccines influences vaccination outcome.

text: We investigated the significance of differing proportions of specific subpopulations among commercial Arkansas (Ark) Delmarva poultry industry (DPI) vaccines with regard to vaccination outcome. Two ArkDPI-derived vaccines that contain a higher proportion of viruses with S1 genes that become selected during replication in chickens exhibited more rapid establishment of those selected subpopulations in chickens, produced significantly higher viral loads in tears, and induced higher antibody responses compared with two other ArkDPI vaccines with lower proportions of viruses that become selected in chickens. The presence of higher proportions of selected subpopulations was also associated with a significantly higher incidence of respiratory signs early after vaccination and in some cases more severe tracheal lesions. However, one of the ArkDPI-derived vaccines with a lower proportion of selected subpopulations, despite producing a lower viral load in tears, also induced a higher incidence of respiratory signs later after vaccination and more severe tracheal lesions. Furthermore, one of the ArkDPI-derived vaccines with a higher proportion of selected subpopulations, despite producing a higher viral loads in tears, resulted in less severe tracheal damage. These discrepancies suggest that infectious bronchitis virus (IBV) load in tears may not always predict degree of tracheal damage and that phenotypic characteristics other than S1 may also be involved in severity of vaccine reactions following ArkDPI vaccine administration. We observed lower antibody responses to the vaccines that produced lower viral loads, which might contribute to the persistence of Ark serotype IBV vaccines observed in commercial flocks.


title: [Clinical Characteristics of Coronavirus Disease 2019 in the Netherlands].

text: Since February, 27 2019, when the first patient with coronavirus disease 2019 (Covid-19) was identified in the Netherlands it has rapidly spread throughout the country. Exactly one month later 8603 people had been tested positive for SARS-CoV-2, 2500 patients were or had been admitted to the hospital and 456 patients died. Here the clinical data are summarized of the first 236 patients that have been admitted to hospitals in Uden, Breda and Tilburg which were all at the centre of the initial outbreak in the Netherlands. This commentary focusses on the clinical characteristics of the patients that are currently being treated on the Dutch clinical corona units, their medical management and the first clinical outcomes. Data is compared to current cohort studies from China, Italy and the United States.


Health assembly rebuffs Taiwan's bid for 'observer' status.


The molecular biology of arteriviruses.


docid: srnnpktl

title: Potent neutralization of Hendra and Nipah viruses by human monoclonal antibodies.

text: Hendra virus (HeV) and Nipah virus (NiV) are closely related emerging viruses comprising the Henipavirus genus of the Paramyxovirinae. Each has a broad species tropism and can cause disease with high mortality in both animal and human hosts. These viruses infect cells by a pH-independent membrane fusion event mediated by their attachment (G) and fusion (F) envelope glycoproteins (Envs). Seven Fabs, m101 to -7, were selected for their significant binding to a soluble form of Hendra G (sG) which was used as the antigen for panning of a large naïve human antibody library. The selected Fabs inhibited, to various degrees, cell fusion mediated by the HeV or NiV Envs and virus infection. The conversion of the most potent neutralizer of infectious HeV, Fab m101, to immunoglobulin G1 (IgG1) significantly increased its cell fusion inhibitory activity: the 50% inhibitory concentration was decreased more than 10-fold to approximately 1 microg/ml. The IgG1 m101 was also exceptionally potent in neutralizing infectious HeV; complete (100%) neutralization was achieved with 12.5 microg/ml, and 98% neutralization required only 1.6 microg/ml. The inhibition of fusion and infection correlated with binding of the Fabs to full-length G as measured by immunoprecipitation and less with binding to sG as measured by enzyme-linked immunosorbent assay and Biacore. m101 and m102 competed with the ephrin-B2, which we recently identified as a functional receptor for both HeV and NiV, indicating a possible mechanism of neutralization by these antibodies. The m101, m102, and m103 antibodies competed with each other, suggesting that they bind to overlapping epitopes which are distinct from the epitopes of m106 and m107. In an initial attempt to localize the epitopes of m101 and m102, we measured their binding to a panel of 11 G alanine-scanning mutants and identified two mutants, P185A and Q191 K192A, which significantly decreased binding to m101 and one, G183, which decreased binding of m102 to G. These results suggest that m101 to -7 are specific for HeV or NiV or both and exhibit various neutralizing activities; they are the first human monoclonal antibodies identified against these viruses and could be used for treatment, prophylaxis, and diagnosis and as research reagents and could aid in the development of vaccines.


title: Using the hierarchy of control technologies to improve healthcare facility infection control: lessons from severe acute respiratory syndrome.

text: Health care facilities need to review their infection control plans to prepare for the possible resurgence of severe acute respiratory syndrome, other emerging pathogens, familiar infectious agents such as tuberculosis and influenza, and bioterrorist threats. This article describes the classic "hierarchy of control technologies" that was successfully used by occupational and environmental medicine professionals to protect workers from illness and death during the resurgence of tuberculosis in the 1990s. Also discussed are related guidelines from building and equipment professional organizations and novel infection control techniques used successfully by various hospitals in Asia, Canada, and the United States during the 2003 severe acute respiratory syndrome epidemic. Taken together, they suggest a framework upon which a comprehensive infection control plan can be crafted to prevent the spread of deadly infectious agents to health care workers (clinicians and paraprofessionals), uninfected patients and visitors.


title: Phase Detection of the Two-port FPW Sensor for Biosensing.

text: In this study, we provided a comprehensive methodology for designing and integrating miniature system in the biosensor application. In general, the network analyzer is commonly used for acoustic wave sensor measurement. However, it is remarkably inconvenient for portable use. Therefore, we presented a readout concept, which was focused on the miniaturization of the flexural plate wave (FPW) sensor system by integrating phase detection circuit. The miniature system includes a Wien-Bridge oscillator, a voltage following, a FPW device, a phase-locked loop, a phase detector, a MCU, and a LCM display. This work succeeded in integrating all the subsystems. And the core technology of the system is the phase detection function. The results showed the phase shift resolution is 10 mV/1°.


title: Experiences and implications of social workers practicing in a pediatric hospital environment affected by SARS.

text: This phenomenological study's purpose was threefold: to detail the experiences of social workers practicing in a hospital environment affected by severe acute respiratory syndrome (SARS), to describe essential themes and structures of social work practices within this crisis environment, and to explore recommendations for better preparedness to meet similar crises in the future. The sudden onset of SARS in hospital settings created an immediate necessity to study this phenomenon as hospitals and health care professionals struggle to adapt to this new epidemic environment. This study is the first using qualitative research to investigate the unique perspective of social workers in an epidemic environment. The results reflect the social workers' subjective experience of their interventions with patients and families and indicate that a number of professional tenets, such as advocacy, family-centered approach, knowledge of systems, open communication, and ethics effectively supported social work practice in a crisis environment.


title: Network analysis in public health: history, methods, and applications.

text: Network analysis is an approach to research that is uniquely suited to describing, exploring, and understanding structural and relational aspects of health. It is both a methodological tool and a theoretical paradigm that allows us to pose and answer important ecological questions in public health. In this review we trace the history of network analysis, provide a methodological overview of network techniques, and discuss where and how network analysis has been used in public health. We show how network analysis has its roots in mathematics, statistics, sociology, anthropology, psychology, biology, physics, and computer science. In public health, network analysis has been used to study primarily disease transmission, especially for HIV/AIDS and other sexually transmitted diseases; information transmission, particularly for diffusion of innovations; the role of social support and social capital; the influence of personal and social networks on health behavior; and the interorganizational structure of health systems. We conclude with future directions for network analysis in public health.


title: The anti-inflammatory and anti-nociceptive activities of Patrinia villosa and its mechanism on the proinflammatory cytokines of rats with pelvic inflammation.

text: This study explores the anti-inflammatory and anti-nociceptive activities of Patrinia villosa, a Chinese medicinal plant, and to explore its effects on the proinflammatory cytokines of the rats with pelvic inflammation model. The animals were randomly divided into Patrinia villosa group (PV group), dexamethasone group (DEX group), and model-control group (CON group) to perform an ear edema test, a carrageenin-induced paw edema test, a cotton pellet-induced granuloma formation test, and an acetic acid-induced writhing test. The model rats with pelvic inflammation were established, and the serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) in each group was detected with the Enzyme-Linked ImmunoSorbent Assay (ELISA). The results of the ear edema test, carrageenin-induced paw edema test, cotton pellet-induced granuloma formation test, and acetic acid-induced writhing test all showed that Patrinia villosa had strong anti-inflammatory and anti-nociceptive effects. In the experiment using model rats with pelvic inflammation, we found that the serum levels of IL-6, IL-8 and TNF-α in PV and DEX group were all significantly lower than those of the CON group, and the serum levels of IL-6 and IL-8 in PV group were significantly lower than those of the DEX group. Patrinia villosa, with its strong anti-inflammatory and anti-nociceptive activities, can be used to treat pelvic inflammation and to relieve the associated pain.


title: Amino acid residues in the cytoplasmic domain of the Mason-Pfizer monkey virus glycoprotein critical for its incorporation into virions.

text: Assembly of an infectious retrovirus requires the incorporation of the envelope glycoprotein complex during the process of particle budding. We have recently demonstrated that amino acid substitutions of a tyrosine residue in the cytoplasmic domain block glycoprotein incorporation into budding Mason-Pfizer monkey virus (M-PMV) particles and abrogate infectivity (C. Song, S. R. Dubay, and E. Hunter, J. Virol. 77:5192-5200, 2003). To investigate the contribution of other amino acids in the cytoplasmic domain to the process of glycoprotein incorporation, we introduced alanine-scanning mutations into this region of the transmembrane protein. The effects of the mutations on glycoprotein biosynthesis and function, as well as on virus infectivity, have been examined. Mutation of two cytoplasmic residues, valine 20 and histidine 21, inhibits viral protease-mediated cleavage of the cytoplasmic domain that is observed during virion maturation, but the mutant virions show only moderately reduced infectivity. We also demonstrate that the cytoplasmic domain of the M-PMV contains three amino acid residues that are absolutely essential for incorporation of glycoprotein into virions. In addition to the previously identified tyrosine at residue 22, an isoleucine at position 18 and a leucine at position 25 each mediate the process of incorporation and efficient release of virions. While isoleucine 18 may be involved in direct interactions with immature capsids, antibody uptake studies showed that leucine 25 and tyrosine 22 are part of an efficient internalization signal in the cytoplasmic domain of the M-PMV glycoprotein. These results demonstrate that the cytoplasmic domain of M-PMV Env, in part through its YXXL-mediated endocytosis and intracellular trafficking signals, plays a critical role in the incorporation of glycoprotein into virions.


title: Successful endovascular extraction of newer generation Angio-Seal collagen plug and anchor after acute embolization.

text: A 75-year-old woman with past medical history of coronary bypass, atrial fibrillation, mitral valve repair undergoes percutaneous coronary intervention of left circumflex artery with a drug eluting stent. An Anglo-Seal vascular closure device was used post procedure to obtain hemostasis. Shortly after deployment, frank bleeding was observed necessitating manual compression at the arteriotomy site. After hemostasis was achieved, the right lower extremity was found to be pale, bluish with feeble pulses. Doppler ultrasound was emergently performed revealing decreased blood flow after mid superficial femoral artery (SFA) and an echo lucent object lodged luminally in the SFA. Patient was urgently taken to the vascular laboratory where an Angio-Seal device, including the collagen plug and anchor, was successfully removed endovascularly patient made full recovery and was discharged home the following day.


title: Viral Pneumonias in Forensic Autopsies: Evaluation and Classification of Histopathologic Changes With Microbiologic Correlation.

text: Lower respiratory infections are commonly due to viruses and are the third largest cause of death. Respiratory tract viruses have a tendency to target the specific regions in the lung and can harm the host via direct effect of the virus and the host's inflammatory response. In this study, relationships between morphologic changes in the lung and the viral agent type isolated in the lung by the polymerase chain reaction technique were investigated. This study was performed retrospectively at 113 autopsy cases in the Council of Forensic Medicine in Istanbul. Slides from the lung tissues diagnosed as interstitial pneumonia and detected viral agent in polymerase chain reaction were evaluated and reviewed under light microscope by 2 pathologists simultaneously according to predetermined bronchiolar, alveolar, and interstitial findings. Alveolar findings were detected in 108 cases (95.6%), whereas interstitial and bronchiolar findings were detected in 91 (80.5%) and 38 (33.6%) cases, respectively. Intra-alveolar edema was the most common alveolar finding. Some findings such as multinucleated syncytial cells and smudge cells can aid the search for etiologic agent. Interstitial inflammation was the most common histopathologic finding in the lung in viral infections and the most prominent clue to viral infections in the lung histopathologically without discrimination of viral agent type.


title: Antibody responses of cattle with respiratory coronavirus infections during pathogenesis of shipping fever pneumonia are lower with antigens of enteric strains than with those of a respiratory strain.

text: The serum antibody responses of cattle with respiratory coronavirus infections during the pathogenesis of shipping fever pneumonia were analyzed with different bovine coronavirus antigens, including those from a wild-type respiratory bovine coronavirus (RBCV) strain (97TXSF-Lu 15-2) directly isolated from lung tissue from a fatally infected bovine, a wild-type enteropathogenic bovine coronavirus (EBCV) strain (Ly 138-3), and the highly cell culture-adapted, enteric prototype strain (EBCV L9-81). Infectivity-neutralizing (IN) and hemagglutinin-inhibiting (HAI) activities were tested. Sequential serum samples, collected during the onset of the respiratory coronavirus infection and at weekly intervals for 5 weeks thereafter, had significantly higher IN and HAI titers for antigens of RBCV strain 97TXSF-Lu15-2 than for the wild-type and the highly cell culture-adapted EBCV strains, with P values ranging from <0.0001 to 0.0483. The IN and HAI antibody responses against the two EBCV strains did not differ significantly, but the lowest titers were detected with EBCV strain L9-81.


title: Equine infectious anemia virus entry occurs through clathrin-mediated endocytosis.

text: Entry of wild-type lentivirus equine infectious anemia virus (EIAV) into cells requires a low-pH step. This low-pH constraint implicates endocytosis in EIAV entry. To identify the endocytic pathway involved in EIAV entry, we examined the entry requirements for EIAV into two different cells: equine dermal (ED) cells and primary equine endothelial cells. We investigated the entry mechanism of several strains of EIAV and found that both macrophage-tropic and tissue culture-adapted strains utilize clathrin-coated pits for entry. In contrast, a superinfecting strain of EIAV, EIAV(vMA-1c), utilizes two mechanisms of entry. In cells such as ED cells that EIAV(vMA-1c) is able to superinfect, viral entry is pH independent and appears to be mediated by plasma membrane fusion, whereas in cells where no detectable superinfection occurs, EIAV(vMA-1c) entry that is low-pH dependent occurs through clathrin-coated pits in a manner similar to wild-type virus. Regardless of the mechanism of entry being utilized, the internalization kinetics of EIAV is rapid with 50% of cell-associated virions internalizing within 60 to 90 min. Cathepsin inhibitors did not prevent EIAV entry, suggesting that the low-pH step required by wild-type EIAV is not required to activate cellular cathepsins.


title: A new laboratory-based surveillance system (Respiratory DataMart System) for influenza and other respiratory viruses in England: results and experience from 2009 to 2012.

text: During the 2009 influenza A(H1N1) pandemic, a new laboratory-based virological sentinel surveillance system, the Respiratory DataMart System (RDMS), was established in a network of 14 Health Protection Agency (now Public Health England (PHE)) and National Health Service (NHS) laboratories in England. Laboratory results (both positive and negative) were systematically collected from all routinely tested clinical respiratory samples for a range of respiratory viruses including influenza, respiratory syncytial virus (RSV), rhinovirus, parainfluenza virus, adenovirus and human metapneumovirus (hMPV). The RDMS also monitored the occurrence of antiviral resistance of influenza viruses. Data from the RDMS for the 2009–2012 period showed that the 2009 pandemic influenza virus caused three waves of activity with different intensities during the pandemic and post pandemic periods. Peaks in influenza A(H1N1)pdm09 positivity (defined as number of positive samples per total number of samples tested) were seen in summer and autumn in 2009, with slightly higher peak positivity observed in the first post-pandemic season in 2010/2011. The influenza A(H1N1)pdm09 virus strain almost completely disappeared in the second postpandemic season in 2011/2012. The RDMS findings are consistent with other existing community-based virological and clinical surveillance systems. With a large sample size, this new system provides a robust supplementary mechanism, through the collection of routinely available laboratory data at minimum extra cost, to monitor influenza as well as other respiratory virus activity. A near real-time, daily reporting mechanism in the RDMS was established during the London 2012 Olympic and Paralympic Games. Furthermore, this system can be quickly adapted and used to monitor future influenza pandemics and other major outbreaks of respiratory infectious disease, including novel pathogens.


docid: himtciob

title: Characterization of nucleocapsid-M protein interaction in murine coronavirus.


title: Structural protein requirements in equine arteritis virus assembly.

text: Equine arteritis virus (EAV) is an enveloped, positive-stranded RNA virus belonging to the family Arteriviridae of the order Nidovirales. EAV particles contain seven structural proteins: the nucleocapsid protein N, the unglycosylated envelope proteins M and E, and the N-glycosylated membrane proteins GP(2b) (previously named G(S)), GP(3), GP(4), and GP(5) (previously named G(L)). Proteins N, M, and GP(5) are major virion components, E occurs in virus particles in intermediate amounts, and GP(4), GP(3), and GP(2b) are minor structural proteins. The M and GP(5) proteins occur in virus particles as disulfide-linked heterodimers while the GP(4), GP(3), and GP(2b) proteins are incorporated into virions as a heterotrimeric complex. Here, we studied the effect on virus assembly of inactivating the structural protein genes one by one in the context of a (full-length) EAV cDNA clone. It appeared that the three major structural proteins are essential for particle formation, while the other four virion proteins are dispensable. When one of the GP(2b), GP(3), or GP(4) proteins was missing, the incorporation of the remaining two minor envelope glycoproteins was completely blocked while that of the E protein was greatly reduced. The absence of E entirely prevented the incorporation of the GP(2b), GP(3), and GP(4) proteins into viral particles. EAV particles lacking GP(2b), GP(3), GP(4), and E did not markedly differ from wild-type virions in buoyant density, major structural protein composition, electron microscopic appearance, and genomic RNA content. On the basis of these results, we propose a model for the EAV particle in which the GP(2b)/GP(3)/GP(4) heterotrimers are positioned, in association with a defined number of E molecules, above the vertices of the putatively icosahedral nucleocapsid.


title: Strategies and mechanisms for host and pathogen survival in acute and persistent viral infections.

text: Persistent viral infections causing serious diseases derive, primarily, from altered function of the immune system. Knowledge of the very complex composition and function of the innate and adaptive branches of the immune system is essential to understanding persistent infection. The best solution to the problem of persistent infection is by prevention using prophylactic vaccines. Hit and run viruses evade immune destruction by infecting new hosts and rarely persist. Hit and stay viruses evade immune control by sequestration, blockade of antigen presentation, cytokine escape, evasion of natural killer cell activities, escape from apoptosis, and antigenic change. Twelve prophylactic vaccines against hit and run agents exist, and there are only three vaccines against hit and stay viruses, all of which are of DNA composition. Several new vaccines against hit and stay viruses are feasible, but protective vaccines against RNA HIV and hepatitis C agents are highly unlikely, short of a major breakthrough. Therapeutic vaccines are very improbable without a magnitude of favorable new discoveries. In the meantime, antiviral chemotherapy, chemotherapy/prophylactic vaccination, and short interfering RNA silencing are worthy of intense investigation.


title: Community-acquired pneumonia in children.

text: PURPOSE OF REVIEW This review highlights recent developments in the diagnosis, etiology, therapy, and prevention of community-acquired pneumonia in children. RECENT FINDINGS Sensitive new diagnostic methods have increased the detection rate of the causative agent up to 94%. Streptococcus pneumoniae is the most prevalent bacterial pathogen in all ages. Polymerase chain reaction is a rapid and sensitive method for the detection of Chlamydia pneumoniae and Mycoplasma pneumoniae, which have gained greater importance in recent years. During the period covered by this review, two new agents causing pneumonia were extensively studied. Human metapneumonovirus detected in young children is a leading cause of respiratory disease during the first years of life. A novel coronavirus was identified as the causative agent of severe respiratory syndrome, a new respiratory illness that affects adults and children. One multicenter trial concluded that nonsevere pneumonia can be treated with a short course of oral amoxicillin and a multicenter international study showed that children with severe pneumonia have similar outcomes whether treated with oral amoxicillin or parenteral penicillin, but more data are needed to demonstrate the safety and efficacy of such regimens. SUMMARY The continued evolution of bacterial resistance highlights the need for appropriate use of antibacterials. Improved diagnostic techniques will aid the treatment of children with community-acquired pneumonia. Aggressive vaccination with the pneumococcal conjugate vaccine and other available vaccines as well as the development of new vaccines will aid the prevention of respiratory disease in children.


title: [Study on the dynamic prevalence of serum antibody against severe acute respiratory syndrome coronavirus in employees from wild animal market in Guangzhou].

text: OBJECTIVE To investigate the dynamic trend of specific antibody against severe acute respiratory syndrome (SARS)-CoV in serum collected at various periods among employees in Guangzhou Xinyuan animal market. METHODS Volunteers from employees of the animal market were recruited and their serum specific antibody against SARS-CoV were determined by enzyme linked immunesorbent assay (ELISA) method. RESULTS Positive SARS-CoV specific IgG antibody was found 25.61% (n = 328), 13.03% (n = 238), 12.59% (n = 135), 5.04% (n = 139) and 9.43% (n = 53) among volunteers, which were sampled in May 2003, Dec. 2003, Jan. 2004, July 2004 and June 2005 respectively. No specific IgM antibody was found in all of those samples. Among 129 samples which were tested twice or more, 97 were all negative, 18 all positive, 13 changed from positive to negative but only one sample from negative to positive. When the volunteers were divided by the duration of their working experiences as short-term or long-term, those who had worked at animal market for less than or more then 6 months when being tested, the positive rate for long-term employees were relatively constant, however, all of the persons employed after January 2004, when the palm civets and raccoon dogs were culled from the market, were tested negative. CONCLUSION The prevalence of specific antibody against SARS-CoV in employees of the animal market were somehow related with the presence or absence of palm civet. No serum was tested positive for persons who were employed after palm civets and raccoon dogs were culled from market. This data indicated that the SARS-CoV might have been from the palm civets and raccoon dog, and the animal market seemed to serve as one of the sources of infection.


title: Acute Bronchitis.

text: Cough is the most common illness-related reason for ambulatory care visits in the United States. Acute bronchitis is a clinical diagnosis characterized by cough due to acute inflammation of the trachea and large airways without evidence of pneumonia. Pneumonia should be suspected in patients with tachypnea, tachycardia, dyspnea, or lung findings suggestive of pneumonia, and radiography is warranted. Pertussis should be suspected in patients with cough persisting for more than two weeks that is accompanied by symptoms such as paroxysmal cough, whooping cough, and post-tussive emesis, or recent pertussis exposure. The cough associated with acute bronchitis typically lasts about two to three weeks, and this should be emphasized with patients. Acute bronchitis is usually caused by viruses, and antibiotics are not indicated in patients without chronic lung disease. Antibiotics have been shown to provide only minimal benefit, reducing the cough or illness by about half a day, and have adverse effects, including allergic reactions, nausea and vomiting, and Clostridium difficile infection. Evaluation and treatment of bronchitis include ruling out secondary causes for cough, such as pneumonia; educating patients about the natural course of the disease; and recommending symptomatic treatment and avoidance of unnecessary antibiotic use. Strategies to reduce inappropriate antibiotic use include delayed prescriptions, patient education, and calling the infection a chest cold.


title: [Analysis of medication characteristics of traditional Chinese medicine in treating COVID-19 based on data mining].

text: OBJECTIVE To analysis the medication characteristics of the prescriptions issued via open channel by the National and Provincial Health Committee and the State Administration of Traditional Chinese Medicine in treating coronavirus disease 2019 (COVID-19). METHODS We collected the data of traditional Chinese medicine related to treatment plans published by the National and Provincial Health Committee and the State Administration of Traditional Chinese Medicine from the start of COVID-19 outbreak to February 19, 2020. The frequency analysis, cluster analysis and association analysis were performed. RESULTS The study collected 4 national and 34 regional prevention and treatment plans, 578 items, 84 traditional Chinese formulations, 60 Chinese patent medicines, and 230 Chinese herbs. The high frequently used herbs were Liquorice, Scutellariabaicalensis, Semen armeniacaeamarae, and Gypsum. The commonly used traditional formulations included Maxing Shigan decoction, Yin Qiao powder, and Xuanbai Chengqi decoction. The Chinese patent drugs included Angong Niuhuang pill, Xuebijing injection, and Lianhua Qingwen capsule. The most common paired medications were Ephedra and Semen armeniacaeamarae, Fructusforsythiae and Liquorice. Two core combinations and one novel formula were discovered in the study. CONCLUSIONS Yin Qiao powder and Huopo Xialing decoction are the basic formulations for Weifen syndrome of COVID-19. In addition, Maxing Shigan decoction, Liang Ge powder, Qingwen Baidu decoction and Da Yuan decoction are the basic formulations for Qifen syndrome of COVID-19. The main medication characteristics are clearing heat, entilating lung, removing toxicity and removing turbidity. It shows that removing toxicity and eliminating evil are the prescription thought in treating epidemic disease of traditional Chinese medicine.


docid: gnoeoixy

title: Autophagy is involved in T cell death after binding of HIV-1 envelope proteins to CXCR4.

text: HIV-1 envelope glycoproteins (Env), expressed at the cell surface, induce apoptosis of uninfected CD4+ T cells, contributing to the development of AIDS. Here we demonstrate that, independently of HIV replication, transfected or HIV-infected cells that express Env induced autophagy and accumulation of Beclin 1 in uninfected CD4+ T lymphocytes via CXCR4. The same phenomena occurred in a T cell line and in transfected HEK.293 cells that expressed both wild-type CXCR4 and a truncated form of CD4 that is unable to bind the lymphocyte-specific protein kinase Lck. Env-mediated autophagy is required to trigger CD4+ T cell apoptosis since blockade of autophagy at different steps, by either drugs (3-methyladenine and bafilomycin A1) or siRNAs specific for Beclin 1/Atg6 and Atg7 genes, totally inhibited the apoptotic process. Furthermore, CD4+ T cells still underwent Env-mediated cell death with autophagic features when apoptosis was inhibited. These results suggest that HIV-infected cells can induce autophagy in bystander CD4+ T lymphocytes through contact of Env with CXCR4, leading to apoptotic cell death, a mechanism most likely contributing to immunodeficiency.


title: Autoimmune disease triggered by infection with alphaproteobacteria.

text: Despite having long been postulated, compelling evidence for the theory that microbial triggers drive autoimmunity has only recently been reported. A specific association between Novosphingobium aromaticivorans, an ubiquitous alphaproteobacterium, and primary biliary cirrhosis (PBC) has been uncovered in patients with PBC. Notably, the association between Novosphingobium infection and PBC has been confirmed in a mouse model in which infection leads to the development of liver lesions resembling PBC concomitant with the production of anti-PDC-E2 antibodies that cross-react with conserved PDC-E2 epitopes shared by Novosphingobium. The discovery of infectious triggers of autoimmunity is likely to change our current concepts about the etiology of various autoimmune syndromes and may suggest new and simpler ways to diagnose and treat these debilitating diseases.


title: Yeast-expressed recombinant protein of the receptor-binding domain in SARS-CoV spike protein with deglycosylated forms as a SARS vaccine candidate.

text: Development of vaccines for preventing a future pandemic of severe acute respiratory syndrome (SARS) caused by SARS coronavirus (SARS-CoV) and for biodefense preparedness is urgently needed. Our previous studies have shown that a candidate SARS vaccine antigen consisting of the receptor-binding domain (RBD) of SARS-CoV spike protein can induce potent neutralizing antibody responses and protection against SARS-CoV challenge in vaccinated animals. To optimize expression conditions for scale-up production of the RBD vaccine candidate, we hypothesized that this could be potentially achieved by removing glycosylation sites in the RBD protein. In this study, we constructed two RBD protein variants: 1) RBD193-WT (193-aa, residues 318-510) and its deglycosylated forms (RBD193-N1, RBD193-N2, RBD193-N3); 2) RBD219-WT (219-aa, residues 318-536) and its deglycosylated forms (RBD219-N1, RBD219-N2, and RBD219-N3). All constructs were expressed as recombinant proteins in yeast. The purified recombinant proteins of these constructs were compared for their antigenicity, functionality and immunogenicity in mice using alum as the adjuvant. We found that RBD219-N1 exhibited high expression yield, and maintained its antigenicity and functionality. More importantly, RBD219-N1 induced significantly stronger RBD-specific antibody responses and a higher level of neutralizing antibodies in immunized mice than RBD193-WT, RBD193-N1, RBD193-N3, or RBD219-WT. These results suggest that RBD219-N1 could be selected as an optimal SARS vaccine candidate for further development.


title: The implementation of a standardized approach to laparoscopic rectal surgery.

text: BACKGROUND AND OBJECTIVES The purpose of this study was to audit our results after implementation of a standardized operative approach to laparoscopic surgery for rectal cancer within a fast-track recovery program. METHODS From January 2009 to February 2011, 100 consecutive patients underwent laparoscopic surgery on an intention-to-treat basis for rectal cancer. The results were retrospectively reviewed from a prospectively collected database. Operative steps and instrumentation for the procedure were standardized. A standard perioperative care plan was used. RESULTS The following procedures were performed: low anterior resection (n = 26), low anterior resection with loop-ileostomy (n = 39), Hartmann's operation (n = 14), and abdominoperineal resection (n = 21). The median length of hospital stay was 7 days; 9 patients were readmitted There were 9 cases of conversion to open surgery. The overall complication rate was 35%, including 6 cases (90/%) of anastomotic leakages requiring reoperation. The 30-day mortality was 5%. The median number of harvested lymph nodes was 15 (range, 2 to 48). There were 6 cases of positive circumferential resection margins. The median follow-up was 9 (range, 1 to 27) months. One patient with disseminated cancer developed port-site metastasis. CONCLUSIONS The results confirm the safety of a standardized approach, and the oncological outcomes are comparable to those of similar studies.


docid: arayxtpo

title: Respiratory syncytial virus infection in adults.

text: Respiratory syncytial virus (RSV) is now recognized as a significant problem in certain adult populations. These include the elderly, persons with cardiopulmonary diseases, and immunocompromised hosts. Epidemiological evidence indicates that the impact of RSV in older adults may be similar to that of nonpandemic influenza. In addition, RSV has been found to cause 2 to 5% of adult community-acquired pneumonias. Attack rates in nursing homes are approximately 5 to 10% per year, with significant rates of pneumonia (10 to 20%) and death (2 to 5%). Clinical features may be difficult to distinguish from those of influenza but include nasal congestion, cough, wheezing, and low-grade fever. Bone marrow transplant patients prior to marrow engraftment are at highest risk for pneumonia and death. Diagnosis of RSV infection in adults is difficult because viral culture and antigen detection are insensitive, presumably due to low viral titers in nasal secretions, but early bronchoscopy is valuable in immunosuppressed patients. Treatment of RSV in the elderly is largely supportive, whereas early therapy with ribavirin and intravenous gamma globulin is associated with improved survival in immunocompromised persons. An effective RSV vaccine has not yet been developed, and thus prevention of RSV infection is limited to standard infection control practices such as hand washing and the use of gowns and gloves.


docid: ffsubocr

title: Highly pathogenic avian flu, Japan.


Is SARS just ARDS?


title: A multiplex RT-PCR test for the differential identification of turkey astrovirus type 1, turkey astrovirus type 2, chicken astrovirus, avian nephritis virus, and avian rotavirus.

text: Recent studies have revealed the presence ofastroviruses and rotavirus in numerous poorly performing and healthy chicken and turkey flocks in the United States. The phylogenetic analysis of the sequence data produced during these studies has identified four groups of avian astroviruses circulating in the United States: turkey astrovirus types 1 and 2 (TAstV-1 and TAstV-2), avian nephritis virus (ANV), and a chicken-origin astrovirus (CAstV). As the molecular epidemiology of poultry enteric disease is poorly understood, the development of updated diagnostic assays is crucial to the continued surveillance and management of enteric disease in affected as well as healthy flocks. This report details the development of a multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) assay specific for astroviruses and avian rotavirus in turkey-origin and chicken-origin samples. The assay consists of two multiplex tests, one for turkey-origin samples and one for chicken-origin samples. The turkey sample test differentially identifies TAstV-1, TAstV-2, ANV, and avian rotavirus. The test for chicken-origin samples differentially identifies CAstV, ANV, and avian rotavirus. Assay sensitivity varied by target sequence between approximately 10 copies for avian rotavirus alone and approximately 2 x 10(6) copies for TAstV-2 in the presence of a heterologous competitor RNA sequence. Each test was shown to be specific for the intended target by testing for cross-reaction with other common avian enteric viruses. The specificity was further shown by testing 109 chicken specimens and 32 turkey specimens from commercial flocks with the appropriate test and sequencing the RT-PCR amplicons to confirm amplification of the correct target.


title: [Thoracic high resolution CT findings of 100 SARS patients in convalescent period].

text: OBJECTIVE To study thoracic high resolution CT findings of severe acute respiratory syndrome (SARS) patients in convalescent period and the relationship between the features with laboratory and pulmonary function results. METHODS All the 100 SARS patients who had been discharged from hospital for about 2 months underwent thoracic high resolution CT examinations. Among them, 65 also had laboratory results and 91 underwent examinations of pulmonary function. RESULTS Forty-nine SARS patients (49.0%, 49/100) in convalescent period still had abnormal findings in CT examination. And ground-glass opacification (95.9%, 47/49) and reticular opacification (59.2%, 29/49) were common. There was no significant difference in the level of lymphocytes and CD4 cells among groups divided according to severity of CT findings (P > 0.01). Diffusing capacity for carbon monoxide (DLco%) of level 2 and 3 were statistically lower than that of level 0 (P < 0.01). CONCLUSIONS The features of CT findings of SARS patients in convalescent period are not the same as those of patients in period of apparent manifestation. The high resolution CT can reflect pulmonary diffusing function to some degree.


title: [SARS-CoV-2, a point in the storm].

text: Since its emergence in December 2019, scientific knowledge about the SARS-CoV-2 virus has evolved rapidly but, due to the complexity and novelty of this infection and its political and economic stakes, much remains to be clarified. Thousands of studies have already been published and scientific research is constantly evolving. In this multitude of information, we offer an update of the knowledge currently available. A limitation of the propagation, the understanding of the functioning of the virus and its clinical manifestations, the administration of specific treatments, rapid and reliable diagnostic tools are the basis of the fight against this germ, which is still little known today.


title: Syphilis in China: results of a national surveillance programme.

text: BACKGROUND After a massive syphilis epidemic in the first half of the 20th century, China was able to eliminate this infection for 20 years (1960-80). However, substantial changes in Chinese society have been followed by a resurgent epidemic of sexually transmitted diseases. Sporadic reports have provided clues to the magnitude of the spread of syphilis, but a national surveillance effort is needed to provide data for planning and intervention. METHODS We collected and assessed case report data from China's national sexually transmitted disease surveillance system and sentinel site network. FINDINGS In 1993, the reported total rate of cases of syphilis in China was 0.2 cases per 100,000, whereas primary and secondary syphilis alone represented 5.7 cases per 100,000 persons in 2005. The rate of congenital syphilis increased greatly with an average yearly rise of 71.9%, from 0.01 cases per 100,000 livebirths in 1991 to 19.68 cases per 100 000 livebirths in 2005. INTERPRETATION The results suggest that a range of unique biological and social forces are driving the spread of syphilis in China. A national campaign for detection and treatment of syphilis, and a credible prevention strategy, are urgently needed.


title: Bound for Sydney town: health surveillance on international cruise vessels visiting the Port of Sydney.

text: A program for routine health surveillance on international cruise ships visiting the Port of Sydney has been developed since 1998. Before introduction of this program, ships only reported quarantinable diseases and were not aware of the Australian requirement to report other infectious diseases. Voluntary routine reporting, developed in partnership with the cruise ship industry, provides timely information on all infectious diseases of public health interest during every cruise. During 1999-2003, the program resulted in detection of and response to 14 outbreaks of gastroenteritis or acute respiratory infection, affecting more than 1400 passengers and crew. The program has improved preventive action, and risk communication and management by cruise ship operators, and led to more timely investigation and support by public health authorities.


Summaries for patients. Do some patients with SARS have mild disease?


Disseminated adenovirus infection in a cat.


title: Infection of polarized epithelial cells with enteric and respiratory tract bovine coronaviruses and release of virus progeny.

text: OBJECTIVE To investigate the susceptibility of polarized epithelioid human rectal tumor (HRT-18G) cells to bovine coronaviruses (BCV) isolated from enteric (EBCV) and respiratory (RBCV) tract infections. PROCEDURE Cells of the G clone of HRT-18 were grown to confluent monolayers on permeable supports, and were directionally infected at the apical and basolateral domains with 3 wild-type BCV strains, RBCV-LSU-94LSS-051-2, RBCV-OK-0514-3, and EBCV-LY138-2, and 1 cell culture-adapted strain, EBCV-L9-80. Sequential cytopathic changes were microscopically monitored. Medium samples for titration of hemagglutinins and viral infectivity were collected directionally from both domains of the infected cell cultures at various intervals. RESULTS Polarized epithelioid HRT-18G cells from apical domains had maximal susceptibility to infection with the EBCV and RBCV strains, and those from basolateral surfaces had minimal susceptibility. Titers of hemagglutinins and infective progeny BCV reached 1,280 hemagglutinin units and 4.2 x 10(8) plaque-forming units/ml for apical samples, but were minimal for basolateral samples. Asymmetric virus release occurred through the apical surfaces of the HRT-18G cells by 12 hours after infection when cell fusion as a sign of cytopathic changes began. When cells were infected basolaterally, progeny virions released from apical surfaces reinfected the target cells from the apical domains and induced cytopathic changes were delayed about 12 hours, compared with changes detectable in apically exposed cultures. CONCLUSIONS EBCV and RBCV, isolated from cattle, had marked tropism for polarized epithelioid HRT-18G cells. Entry of BCV into the polarized HRT-18G cells was effected maximally through the apical domains and minimally through the basolateral domains. Release of progeny BCV occurred preferentially from the apical domains.


title: [Clinical features of children with SARS-CoV-2 infection: an analysis of 115 cases].

text: OBJECTIVE To study the clinical features of children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS A retrospective analysis was performed for the clinical data of 115 children who were diagnosed with SARS-CoV-2 infection in the Wuhan Children's Hospital, including general information, history of close contact with individuals of SARS-CoV-2 infection, early clinical symptoms, laboratory examination results, and lung CT results. RESULTS Among the 115 children, there were 73 boys (63.5%) and 42 girls (36.5%), with a male/female ratio of 1:0.58. Of the 115 children, 105 (91.3%) had a definite history of close contact with individuals of SARS-CoV-2-infection. An increase in alanine aminotransferase was observed in 11 children (9.6%) and an increase in CK-MB was found in 34 children (29.6%). As for clinical symptoms, 29 children (25.2%) had fever, 47 (40.9%) had respiratory symptoms (including cough, rhinorrhea, and nasal congestion), and 61 (53.0%) were asymptomatic. Lung CT findings showed ground glass opacity, fiber opacities, patchy changes, and pulmonary consolidation in 49 children (42.6%), among whom 2 children had "white lung"; 39 children (33.9%) only had lung texture enhancement and 27 children (23.5%) had no pulmonary imaging changes. Among the 115 children, 3 were critically ill, among whom 1 had been cured and the other 2 were under continuous treatment. CONCLUSIONS Most of the children with SARS-CoV-2 infection have a close contact history. Critical cases are rare and there is a high proportion of asymptomatic infection.


title: Raising standards while watching the bottom line: making a business case for infection control.

text: While society would benefit from a reduced incidence of nosocomial infections, there is currently no direct reimbursement to hospitals for the purpose of infection control, which forces healthcare institutions to make economic decisions about funding infection control activities. Demonstrating value to administrators is an increasingly important function of the hospital epidemiologist because healthcare executives are faced with many demands and shrinking budgets. Aware of the difficulties that face local infection control programs, the Society for Healthcare Epidemiology of America (SHEA) Board of Directors appointed a task force to draft this evidence-based guideline to assist hospital epidemiologists in justifying and expanding their programs. In Part 1, we describe the basic steps needed to complete a business-case analysis for an individual institution. A case study based on a representative infection control intervention is provided. In Part 2, we review important basic economic concepts and describe approaches that can be used to assess the financial impact of infection prevention, surveillance, and control interventions, as well as the attributable costs of specific healthcare-associated infections. Both parts of the guideline aim to provide the hospital epidemiologist, infection control professional, administrator, and researcher with the tools necessary to complete a thorough business-case analysis and to undertake an outcome study of a nosocomial infection or an infection control intervention.


docid: yympgnfe

title: Potential Treatments for COVID-19; a Narrative Literature Review.

text: SARS-CoV-2 is a newly emerging human infectious coronavirus that causes COVID-19, which has been recognized as a pandemic by the World Health Organization (WHO) on March 11th. There is still no vaccine or definitive treatment for this virus because its pathogenesis and proliferation pathways are still unknown. Therefore, in this article, new potential COVID-19 therapies are briefly reviewed.


title: Coronavirus multiplication: locations of genes for virion proteins on the avian infectious bronchitis virus genome.

text: Six overlapping viral RNAs are synthesized in cells infected with the avian coronavirus infectious bronchitis virus (IBV). These RNAs contain a 3'-coterminal nested sequence set and were assumed to be viral mRNAs. The seven major IBV virion proteins are all produced by processing of three polypeptides of ca. 23, 51, and 115 kilodaltons. These are the core polypeptides of the small membrane proteins, the nucleocapsid protein, and the 155-kilodalton precursor to the large membrane proteins GP90 and GP84, respectively. To determine which mRNAs specify these polypeptides, we isolated RNA from infected cells and translated it in a messenger-dependent rabbit reticulocyte lysate. Proteins of 23, 51, and 110 kilodaltons were produced. Two-dimensional tryptic peptide mapping demonstrated that these proteins were closely related to the major virion proteins. Fractionation of the RNA before cell-free translation permitted the correlation of messenger activities for synthesis of the proteins with the presence of specific mRNAs. We found that the smallest RNA, RNA A, directs the synthesis of P51, the nucleocapsid protein. RNA C, which contains the sequences of RNA A, directs the synthesis of the small membrane protein P23. RNA E directs the synthesis of the large virion glycoproteins. These results supported a model in which only the unique 5'-terminal domain of each IBV mRNA is active in translation and enabled us to localize genes for virion proteins on the IBV genome.


title: Role of the stable signal peptide of Junín arenavirus envelope glycoprotein in pH-dependent membrane fusion.

text: The envelope glycoprotein of the arenaviruses (GP-C) is unusual in that the mature complex retains the cleaved, 58-amino-acid signal peptide. Association of this stable signal peptide (SSP) has been shown to be essential for intracellular trafficking and proteolytic maturation of the GP-C complex. We identify here a specific and previously unrecognized role of SSP in pH-dependent membrane fusion. Amino acid substitutions that alter the positive charge at lysine K33 in SSP affect the ability of GP-C to mediate cell-cell fusion and the threshold pH at which membrane fusion is triggered. Based on the presumed location of K33 at or near the luminal domain of SSP, we postulate that SSP interacts with the membrane-proximal or transmembrane regions of the G2 fusion protein. This unique organization of the GP-C complex may suggest novel strategies for intervention in arenavirus infection.


title: Single-Cell Studies of Phage λ: Hidden Treasures Under Occam's Rug.

text: Studies over more than half a century have resulted in what some consider a complete narrative for the life cycle of bacteriophage λ. However, this narrative is only complete within the limited resolution offered by the traditional genetic and biochemical approaches that were used to create it. A recent series of studies performed at the single-cell and single-phage levels has revealed a wealth of previously unknown features. By pointing to many open questions, these new studies highlight the limitations of our current understanding of λ, but they also initiate the process of forming a more detailed and quantitative narrative for the system.


title: [The use of genetic engineering in veterinary medicine with examples from epidemiology, diagnosis and drug production].

text: The results of genetic engineering have reached practical veterinary medicine already. Nevertheless there is a great lack of knowledge among those veterinarians who usually do not work with these methods. Therefore we want to give an introduction into the advantages and dangers of this technology concerning veterinary medicine. Some important analytical methods are explained. Related viruses such as WEE and EEE or canine parvovirus, feline parvovirus and mink enteritis virus, or the related coronaviruses FIPV and TGEV serve as examples for the possibilities in molecular diagnosis and epidemic monitoring. The history of the gl- mutants of PRV, now prescribed as vaccine strains in the FRG, is an example of the development of genetic engineered vaccines. A new generation of vaccines based on recombinant vaccinia viruses is imminent. Thus we have to be aware of the high risks and responsibility of everybody who is involved in these new systems, especially the scientist who produces genetically altered organisms.


Specific cleavage of 28S ribosomal RNA in murine coronavirus-infected cells.


title: Fatal 2009 pandemic influenza A (H1N1) in a bone marrow transplant recipient.

text: Conditions characterized by immunosuppression have been recently reported as risk factors for severe novel swine-origin influenza A (H1N1) virus (S-OIV) infection during the current 2009 pandemic. We report clinical and virological findings, antiviral therapy, and post-mortem study of S-OIV in an adult bone marrow transplant recipient. The viral genome was amplified by real time reverse transcriptase polymerase chain reaction (RT-PCR) from a nasopharyngeal swab specimen. The patient developed acute respiratory distress syndrome, septic shock, and eventually succumbed with a severe pulmonary haemorrhage. To the best of our knowledge, the entire clinical/therapy management and pathological examination in a transplant recipient infected with the S-OIV has not been previously documented. The fatal ending in this bone marrow transplant recipient supports recommendations that call for education measures, S-OIV vaccination, early diagnosis and aggressive treatment in the transplant population.


docid: vherpolo

title: COVID-19 and Cancer Patients.

text: COVID-19 has now been declared a global pandemic with evolving incidence rates and fatalities. It is important to identify vulnerable populations who will be impacted most by this pandemic leading to higher mortality rates compared to the general healthy population. Although older patients and patients with co-morbidities fall into this vulnerable group, patients with hematologic and oncologic malignancies on active cytotoxic treatments are at even greater risk as they are both myelosuppressed and immunosuppressed. In addition to following the universal guidelines recommended by the Centers for Disease Control (CDC), it is important to also institute guidelines for cancer centers to help protect this vulnerable population. We review the current data, risks, and recommendations for COVID-19 in cancer patients.


title: Importance of primer selection in the application of PCR technology to the diagnosis of bovine leukemia virus.

text: The polymerase chain reaction (PCR) was used to detect bovine leukemia virus in bovine blood samples. When applied to leucocytes extracted from the blood samples, the standard method of DNA extraction gave good correlation with agar gel immunodiffusion, but a method in which 5 microliters of blood was the starting material was unreliable. Selection of the primers was important, and differences in results were observed when the PCR method was applied to blood samples from different geographic areas. The sensitivity varied from 50% to 90%, depending on the primer set applied to the gag gene of proviral nucleic acid. This variation was based on geographic origin of the cattle, suggesting an influence of viral strain. In some areas, more than 1 primer may needed to optimize results.


Peak expiratory flow (PEF) monitoring.


title: Gamma interferon-dependent, noncytolytic clearance of sindbis virus infection from neurons in vitro.

text: Due to the nonrenewable nature of neurons, recovery from viral infection of the central nervous system requires noncytopathic mechanisms for control of virus replication. Recovery from alphavirus encephalitis can occur without apparent neurological damage through the effects of antibody and gamma interferon (IFN-gamma). To establish an in vitro cell culture system that will allow the study of mechanisms of IFN-gamma-mediated control of Sindbis virus (SINV) replication in neurons, we have characterized the susceptibility to SINV infection and IFN-gamma responsiveness of two neuronal cell lines that can be differentiated in vitro: CSM14.1, a rat nigral cell line, and NSC34, a mouse motor neuron cell line. Undifferentiated CSM14.1 and NSC34 cells were permissive for SINV and susceptible to virus-induced cell death. With differentiation, CSM14.1 cells reduced virus replication and became progressively resistant to virus-induced cell death, resulting in prolonged virus replication. NSC34 cells did not differentiate completely and became only partially resistant to SINV infection. Both CSM14.1 and NSC34 cells responded to pretreatment with IFN-gamma by decreasing SINV replication. Differentiated CSM14.1 cells treated 24 h after infection with IFN-gamma responded with increased cell viability and clearance of infectious virus. IFN-gamma treatment sequentially altered the ratio of genomic to subgenomic viral RNA synthesis, promoted recovery of cellular protein synthesis, reduced viral protein synthesis, and inhibited viral RNA transcription within 24 h after treatment. We conclude that CSM14.1 cells provide an excellent model for the study of IFN-gamma-mediated noncytolytic clearance of SINV from mature neurons.