title: A pneumo-virulent United States isolate of porcine reproductive and respiratory syndrome virus induces apoptosis in bystander cells both in vitro and in vivo.

text: Evidence of apoptosis was detected for the United States porcine reproductive and respiratory syndrome virus (PRRSV) in ATCC CRL11171 cells inoculated with strain ATCC VR2385 and in the tissues of pigs infected with the same strain. Apoptosis was detected by agarose gel electrophoresis, transmission electron microscopy and terminal deoxytransferase dUTP nick end labelling (TUNEL) techniques. By electron microscopy and double-labelling techniques, apoptosis was detected primarily in uninfected bystander cells in the continuous cell line rather than the PRRSV-infected cells. In the lungs, the apoptotic cells were predominantly alveolar and pulmonary intravascular macrophages, and mononuclear cells in the alveolar septa. In the lymph nodes, the apoptotic cells were predominantly tingible body macrophages and mononuclear cells. The induction of apoptosis in a large number of mononuclear cells in the lungs and lymph nodes appears to be a mechanism of PRRSV pathogenesis and might be an explanation for a dramatic reduction in the number of alveolar macrophages and circulating lymphocytes and monocytes in PRRSV-infected pigs.


title: HLA class I transgenic mice: development, utilisation and improvement.

text: Classical major histocompatibility complex (MHC) class I antigens are trimeric molecules found on the surface of nucleated cells in all jawed vertebrates. MHC I are recognised by two families of receptors: clonotypic T cell receptors expressed on the surface of CD8+ cytotoxic T lymphocytes (CTLs), and monomorphic receptors expressed by both natural killer cells and CTLs. The production of MHC I molecules within the cells is a sequential process performed with the help of interacting proteins: proteases, chaperones, transporters and so on. Although largely homologous in their structure, organisation and function, the human and mouse MHC I antigen processing and presentation machineries show fine differences. Transgenesis and 'knockout' or 'knock-in' technologies permit the addition of relevant human genes or the replacement of mouse genes by their human orthologues in order to produce immunologically humanised mice. Such experimental animals are especially relevant for the comparative evaluation of immunotherapies and for the characterisation of MHC I peptide epitopes. This review presents the similarities and differences between mouse and human MHC I antigen processing machinery, and describes the development and utilisation of improving mouse models of human cytotoxic T cell immunity.


title: The role of the obstetrician-gynecologist in emerging infectious diseases: monkeypox and pregnancy.

text: Early in June 2003, the Centers for Disease Control and Prevention (CDC) announced yet another unique infectious disease outbreak, the first evidence of community-acquired monkeypox in the United States. By July 8, 2003, a total of 71 cases had been reported to CDC from 6 states. When emerging infectious diseases are reported in the United States, particularly when these reports receive widespread media attention, obstetrician-gynecologists may be called upon to rapidly respond to queries from their patients and to address certain infectious disease risks within their clinical practices. In addition, obstetrician-gynecologists may have specific concerns about the implications for an infectious disease outbreak, such as monkeypox, for pregnant women. Therefore, it is important that obstetrician-gynecologists know how to gather up-to-date and accurate information about infectious disease outbreaks and that they be familiar with the public health response system for responding to such outbreaks.


title: Replicative adenoviruses for cancer therapy.

text: Rapid advances are being made in the engineering of replication-competent viruses to treat cancer. Adenovirus is a mildly pathogenic human virus that propagates prolifically in epithelial cells, the origin of most human cancers. While virologists have revealed many details about its molecular interactions with the cell, applied scientists have developed powerful technologies to genetically modify or regulate every viral protein. In tandem, the limited success of nonreplicative adenoviral vectors in cancer gene therapy has brought the old concept of adenovirus oncolysis back into the spotlight. Major efforts have been directed toward achieving selective replication by the deletion of viral functions dispensable in tumor cells or by the regulation of viral genes with tumor-specific promoters. However, the predicted replication selectivity has not been realized because of incomplete knowledge of the complex virus-cell interactions and the leakiness of cellular promoters in the viral genome. Capsid modifications are being developed to achieve tumor targeting and enhance infectivity. Cellular and viral functions that confer greater oncolytic potency are also being elucidated. Ultimately, the interplay of the virus with the immune system will likely dictate the success of this approach as a cancer therapy.


Fine structure of primary liver tumors and tumor-bearing livers in man.


title: [Field study of the prevalence and diagnosis of diarrhea-causing agents in the newborn calf in a Swiss veterinary practice area].

text: The prevalence of cryptosporidia, rotavirus, bovine coronavirus and Escherichia coli F5 (K99) in dairy calves with diarrhea and in healthy calves was established in a limited area served by a veterinary practice. Immuno-chromatographic rapid tests (FASTest Strips) were applied in the field and their results were compared to the ones obtained with standard methods (modified Ziehl-Neelsen stain, antigen-ELISA and cultivation). In 78% of the calves with diarrhea (n=46) and in 29% of the healthy calves (n=14), one or two agents were isolated. Of the diseased calves, 43% excreted cryptosporidia and in 46% rotavirus was isolated. Bovine corona virus and Escherichia coli F5 (K99) seemed to be of minor importance in the investigated population. Compared to the modified Ziehl-Neelsen stain or the antigen-ELISA, the FASTest Strips CRYPTO and ROTA were of very high diagnostic specificity of 100% each and their diagnostic sensitivity was 75% and 57%, respectively. Due to the low number of cases, the results of the FASTest Strips BCV and E.coli-K99 could not be interpreted. Although the diagnostic sensitivity of the FASTest Strips CRYPTO and ROTA--evaluated with standard methods--was not very high, their use in calves with acute diarrhea is recommended.


title: Reporting ethics committee approval and patient consent by study design in five general medical journals.

text: BACKGROUND Authors are required to describe in their manuscripts ethical approval from an appropriate committee and how consent was obtained from participants when research involves human participants. OBJECTIVE To assess the reporting of these protections for several study designs in general medical journals. DESIGN A consecutive series of research papers published in the Annals of Internal Medicine, BMJ, JAMA, Lancet and The New England Journal of Medicine between February and May 2003 were reviewed for the reporting of ethical approval and patient consent. Ethical approval, name of approving committee, type of consent, data source and whether the study used data collected as part of a study reported elsewhere were recorded. Differences in failure to report approval and consent by study design, journal and vulnerable study population were evaluated using multivariable logistic regression. RESULTS Ethical approval and consent were not mentioned in 31% and 47% of manuscripts, respectively. 88 (27%) papers failed to report both approval and consent. Failure to mention ethical approval or consent was significantly more likely in all study designs (except case-control and qualitative studies) than in randomised controlled trials (RCTs). Failure to mention approval was most common in the BMJ and was significantly more likely than in The New England Journal of Medicine. Failure to mention consent was most common in the BMJ and was significantly more likely than in all other journals. No significant differences in approval or consent were found when comparing studies of vulnerable and non-vulnerable participants. CONCLUSION The reporting of ethical approval and consent in RCTs has improved, but journals are less good at reporting this information for other study designs. Journals should publish this information for all research on human participants.


title: Globalization of infectious diseases: the impact of migration.

text: With up to 2% of the world's population living outside of their country of birth, the potential impact of population mobility on health and on use of health services of migrant host nations is increasing in its importance. The drivers of mobility, the process of the international movement, and the back-and-forth transitioning between differential risk environments has significance for the management of infectious diseases in migrant receiving areas. The management issues are broad, high-level, and cross-cutting, including policy decisions on managing the migration process for skilled-labor requirements, population demographic and biometric characteristics, and family reunification; to program issues encompassing health care professional education, training, and maintenance of competence; communication of global events of public health significance; development of management guidelines, particularly for nonendemic diseases; access to diagnostic and therapeutic interventions for exotic or rare clinical presentations; and monitoring of health service use and health outcomes in both the migrant and local populations.


title: Infectious and parasitic diseases of captive carnivores, with special emphasis on the black-footed ferret (Mustela nigripes).

text: Captive carnivores are susceptible to a wide array of infectious and parasitic diseases, which reflects the diversity of the seven families of Carnivora. Unfortunately, relatively few in-depth studies have been conducted on diseases of non-domestic carnivores, and much remains to be learned, especially regarding diseases of small carnivores (e.g. mustelids, viverrids and procyonids). The more important infectious diseases of carnivores include rabies, canine distemper, and diseases caused by parvoviruses, coronaviruses and herpesviruses. Few parasitic or bacterial pathogens are significant in captive populations, and appropriate husbandry, therapy, vaccines and quarantine minimize the risk of disease. Extrapolations from one species to another regarding disease susceptibility may be incorrect. The black-footed ferret (Mustela nigripes) serves as an example of a carnivore significantly affected by infectious diseases, some of which were expected while others could not have been predicted from generalized knowledge of diseases of mustelids. This highlights the need to understand the natural history of each species maintained in captivity.


title: Altered metabolism, acute shock, and therapeutic response in a calf with severe coronavirus-induced diarrhea.

text: Acute shock and metabolic failure appeared in a diarrheic calf being studied intensively to determine kinetics of glucose and lactate metabolism. Intravenous therapy significantly improved its condition. During metabolic failure, the rapid increase in blood lactate and concomitant decrease in glucose were due to inhibited gluconeogenesis, as glucose entry and lactate oxidation were not modified. Therapy restored metabolic activity and decreased the severe hyperkalemia.


title: Population proteomics: addressing protein diversity in humans.

text: In the past several years, proteomics and its subdiscipline clinical proteomics have been engaged in the discovery of the next generation protein of biomarkers. As the effort and the intensive debate it has sparked continue, it is becoming apparent that a paradigm shift is needed in proteomics in order to truly comprehend the complexity of the human proteome and assess its subtle variations among individuals. This review introduces the concept of population proteomics as a future direction in proteomics research. Population proteomics is the study of protein diversity in human populations. High-throughput, top-down mass spectrometric approaches are employed to investigate, define and understand protein diversity and modulations across and within populations. Population proteomics is a discovery-oriented endeavor with a goal of establishing the incidence of protein structural variations and quantitative regulation of these modifications. Assessing human protein variations among and within populations is viewed as a paramount undertaking that can facilitate clinical proteomics' effort in discovery and validation of protein features that can be used as markers for early diagnosis of disease, monitoring of disease progression and assessment of therapy. This review outlines the growing need for analyzing individuals' proteomes and describes the approaches that are likely to be applied in such a population proteomics endeavor.


title: New antiviral drugs, vaccines and classic public health interventions against SARS coronavirus.

text: Severe acute respiratory syndrome (SARS) is caused by one of two recently discovered coronaviruses. The virus is emergent from South East (SE) Asian mammals: either the civet cat, a related species or a rat species. The virus has a long incubation period and low reproduction number (R0 value) and hence the first outbreak in 2004 was controlled by hygiene and quarantine. However, the healthcare system was compromised and the economic cost was extremely high. Fortunately, the virus is easily cultivated in Vero E6 cells and therefore the search for new antivirals and vaccines was initiated within weeks of the discovery of the virus using classic techniques of cell culture and electron microscopy. Molecular diagnostics facilitated rapid and accurate diagnosis, a key factor in containing the outbreak. The broad-spectrum molecule ribavirin was used in SE Asia in infected patients alongside corticosteroids. In retrospect, many patients survived due to careful nursing. The only currently accepted intervention is interferon. Coronavirus replicon systems should facilitate rapid screening of new inhibitors and the complex mechanism of viral replication will ensure that drugs are developed against at least five molecular targets, in particular the viral protease.


title: Dynamic observation of the three-dimensional distribution of labeled liposomes using the novel high-resolution single-photon emission computed tomography.

text: The aim of this study was to show that the multipinhole technique (high-resolution single-photon emission computed tomography [HiSPECT]) is suitable for dynamic imaging of both biodistribution and temporal uptake behavior of radiolabeled cationic liposomes in Balb/c-mice. HiSPECT uses multipinhole collimators adapted to a clinical SPECT scanner, together with a dedicated iterative reconstruction program. This technique provides both high spatial resolution and an improvement in sensitivity. Six male Balb/c mice received 9.8 +/- 4.0 MBq of the In 111-labeled liposomes. The measurements started directly after the injection and tomographic data were acquired in steps of 5 minutes. The regional evaluation displayed a high initial uptake of liposomes in the lungs (45.4%), which decreased to 25.1% after 30 minutes and to below 2% after 48 hours. In contrast, liver uptake increased in the first 30 minutes from 13.1 to 21.2% and remained relatively stable at 24.4% (24 hours) and 18.8% (48 hours). The data are interpreted as a slow shift of liposomes from the lungs into the liver and later to other organs such as the spleen and bladder. This study shows that the HiSPECT technique is capable of dynamically visualizing the uptake behavior of radioactively labeled liposomes in vivo with high temporal and spatial resolution.


title: Coronaviruslike particles in human gastrointestinal disease. Epidemiologic, clinical, and laboratory observations.

text: Coronaviruslike particles (CVLPs) were visualized by direct electron microscopy (EM) of diarrheal stools in 49 of 126 infants and children between 1 month and 12 years of age during a three-year observation period. The clinical and epidemiologic features of these patients were analyzed and compared with patients with diarrhea who were shedding rotaviruses, or whose stools were negative for enteric viruses by EM. Seasonal and age distributions for CVLP shedding were similar to those for rotaviruses (in most cases less than 1 year of age; peak months were September through January), as were the symptoms and median durations of illness. Prospective studies of three subsequent patients suggest that the duration of shedding in acute illness is five to at least 25 days. Multiple attempts to cultivate the CVLPs were unsuccessful. In addition, partial purification of CVLPs from stool specimens was performed, and immunologic analysis by immunoelectron microscopy and radial immunodiffusion showed no antigenic relatedness to prototype human (OC43 and 229E) or animal (bovine and canine) coronaviruses. These findings suggest that CVLPs may be an important cause of acute gastrointestinal illness in infancy, and may represent a virus antigenically unrelated to known human and animal coronaviruses.


title: The mental health of hospital workers dealing with severe acute respiratory syndrome.

text: BACKGROUND The aim of this study was to explore the impact of the severe acute respiratory syndrome (SARS) on health care workers in Taiwan. The possible predisposing and perpetuating factors in developing mental symptoms were investigated. METHODS Participantsconsisted of 135 health care workers who had had contact with or took care of patients who were probable or suspected SARS cases, during the SARS outbreak, at a teaching hospital in southern Taiwan. All participants completed questionnaires, including the Chinese Health Questionnaire, Eysenck Personality Questionnaire and Parental Bonding Instrument. RESULTS Twenty-two participants (17.3%) developed significant mental symptoms, and 105 participants (82.7%) showed no obvious symptoms. The structural equation model showed that maternal care (beta = -0.18, p = 0.011) and neuroticism (beta = 0.54, p < 10(-6)) directly influenced the ability of health care workers to deal with the impact of SARS. Maternal overprotection (beta = 0.30, p < 10(-4)) had an indirect influence on the ability to cope with the impact of SARS. CONCLUSION Both neuroticism and maternal attachment influenced the mental health of health care workers during the SARS epidemic. The results can be a helpful reference for intervention and prevention programs for health care workers facing disasters in the future.


title: The hazards of surgical smoke.

text: Surgical smoke is a part of the environment during operative and invasive procedures. As lasers and electrosurgery have become commonplace, perioperative practitioners are at increased risk for health concerns associated with exposure to surgical smoke. Since the mid 1970s, the body of evidence documenting the hazardous components of surgical smoke has continued to grow. Despite the evidence and recommendations of a variety of organizations, there are no uniform requirements mandating surgical smoke evacuation. This article reviews current research to identify the potential health hazards as well as the current recommendations related to the filtration and evacuation of surgical smoke.


title: Ethical considerations in the management of Ebola virus disease.

text: Is it ethically appropriate in some circumstances for HCWs to decline to care for patients with EVD? How should treatment decisions be made regarding limitation of therapy for patients with EVD? There are two main ethical questions regarding the critical care of patients with EVD in an Australian setting: Is it ethically appropriate in some circumstances for HCWs to decline to care for patients with EVD? How should treatment decisions be made regarding limitation of therapy for patients with EVD? The key concern is ensuring that no patient is denied therapy that should be provided, while preventing unnecessary risk to HCWs. It is imperative to develop an approach that facilitates rigorous, evidence-based and ethically justifiable decision making, which should include a predetermined, institutionally endorsed process for assessing difficult clinical scenarios as they arise.


title: Hemagglutinin (HA) proteins from H1 and H3 serotypes of influenza A viruses require different antigen designs for the induction of optimal protective antibody responses as studied by codon-optimized HA DNA vaccines.

text: Effective antibody responses provide crucial immunity against influenza virus infection. The hemagglutinin (HA) protein is the major target of protective antibody responses induced by viral infection and by vaccination with both inactivated and live-attenuated flu vaccines, but knowledge about the optimal designs of protective HA antigens from different flu serotypes is still limited. In this study, we have significantly improved the immunogenicity of HA-expressing DNA vaccines by using codon-optimized HA sequences for either an H1 serotype (A/NewCal/20/99) or an H3 serotype (A/Panama/2007/99) human influenza A virus and then used these constructs as model antigens to identify the optimal HA antigen designs to elicit high-level protective antibody responses. Two forms of HA antigen, a wild-type, full-length HA and a secreted form with transmembrane (TM) domain-truncated HA, were produced. Both forms of HA DNA vaccines, from either H1 or H3 serotypes, were able to elicit high levels of HA-specific immunoglobulin G responses in immunized rabbits as measured by enzyme-linked immunosorbent assay. Interestingly, the abilities of H1 HA and H3 HA antigens to elicit hemagglutination inhibition (HI) and neutralizing antibody (NAb) responses differ. For the H1 HA antigens, the full-length HA induced significantly higher HI and NAb responses than did the TM-truncated HA. For the H3 HA antigen, both the full-length HA and TM-truncated HA induced high levels of HI and NAb responses. These data indicate that H1 and H3 antigens have different expression requirements for the induction of an optimal protective antibody response and that the structure integrity of HA antigens is critical for eliciting type-specific protective antibody responses. Our findings will have an important impact on future subunit-based flu vaccine development.


The psychological impact of SARS: a matter of heart and mind.


title: Neutralization-resistant variants of a neurotropic coronavirus are generated by deletions within the amino-terminal half of the spike glycoprotein.

text: Neuroattenuated variants of mouse hepatitis virus type 4 (MHV-4) selected for resistance to neutralizing monoclonal antibodies (R.G. Dalziel, P.W. Lampert, P. J. Talbot, and M. J. Buchmeier, J. Virol. 59:463-471, 1986) were found to harbor large deletions in both mRNA 3 and its protein product, the 180-kilodalton viron spike (S) glycoprotein. By using antipeptide antibodies directed against selected portions of the chain, deletions were mapped to the middle of the amino-terminal S1 fragment, one of the two posttranslational cleavage products of S, and involved omission of 15 kilodaltons of protein. Deletion mutants could be selected only after multiple passage of virus through cultured cell lines; minimally passaged MHV-4 stocks contained putative point mutants selectable by neutralizing monoclonal antibodies but no deletions. Enhanced growth of deletion mutants relative to wild-type virus was observed in four cell lines used for virus propagation and was attributed to delayed and diminished cytopathic effects that allowed cultures to support virus production for prolonged periods. This hypothesis was reinforced by the finding that no selective advantage for the deletion mutants was observed in two cell lines resistant to virus-induced cytopathic effects. These results indicate that the passaging of MHV-4 in culture generates heterogeneity in S structure and eventually selects for rare neutralization-resistant deletion mutants with decreased virulence properties.


title: Pulmonary function and exercise capacity in survivors of severe acute respiratory syndrome.

text: The aim of this study was to investigate pulmonary function and exercise capacity in a group of survivors of the severe acute respiratory syndrome (SARS). At 3 months after hospital discharge, 46 survivors of SARS underwent the following evaluation: spirometry, static lung volumes and carbon monoxide transfer factor (TL,CO). In total, 44 of these patients underwent cardiopulmonary exercise testing. No abnormalities were detected in the pulmonary function tests in 23 (50%) of the patients. Abnormalities of forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC and TL,CO were detected in seven (15%), 12 (26%), one (2%) and 18 (39%) patients, respectively. All of these abnormalities were mild except in one case. In 18 patients (41%), the maximum aerobic capacity was below the lower limit of the normal range. Breathing reserve was low in four patients and significant oxygen desaturation was detected in a further four patients. Comparison of the measured exercise capacity with resting pulmonary function tests showed many cases of discordance in impairment. In conclusion, pulmonary function defects were detected in half of the recovered severe acute respiratory syndrome patients 3 months after hospital discharge, but the impairment was mild in almost all cases. Many patients had reduced exercise capacity that cannot be accounted for by impairment of pulmonary function.


title: Immunity to fungal infections.

text: The topic of immunity to fungal infections is of interest to a wide range of disciplines, from microbiology to immunology. It is of particular interest in terms of therapy of HIV-infected individuals, and patients with cancer or individuals who have received transplants. Understanding the nature and function of the immune response to fungi is an exciting challenge that might set the stage for new approaches to the treatment of fungal diseases, from immunotherapy to vaccines. The past decade has witnessed the development of a wide range of new approaches to elucidate events that occur at the host-fungus interface.


title: SARS: an emerging global microbial threat.

text: In March 2003, the Institute of Medicine published an update to its 1992 landmark report on emerging infections. The new report, Microbial Threats to Health: Emergence, Detection, and Response, describes the current spectrum of global microbial threats, factors affecting their emergence or resurgence, and measures that should be undertaken to effectively address them. Coincident with this publication came increasing reports of severe atypical pneumonia of unknown etiology among persons in southeast Asia. This new disease, designated severe acute respiratory syndrome (SARS), spread globally in a matter of weeks, infecting primarily close contacts of index patients (e.g., household members and healthcare workers caring for index patients) but also resulting in community transmission in some areas. An unprecedented worldwide collaborative effort was undertaken to determine the cause of the illness and implement prevention measures. A previously unrecognized coronavirus was identified as the causative agent, and health officials throughout the world struggled to implement measures to contain its spread, including isolation of suspect SARS cases and quarantine of exposed persons. The emergence of SARS is a timely reminder of the need to expect the unexpected and to ensure strong national and global public health partnerships when preparing for and responding to infectious diseases. Effectively addressing the threat of SARS will require enhanced global infectious disease surveillance, the development of rapid diagnostics, new therapies, and vaccines, implementation of aggressive evidence-based infection control strategies, and effective communication.


title: Chest radiographic findings of a case of severe acute respiratory syndrome (SARS) in Singapore.

text: A new form of atypical pneumonia was reported in the East Asian region beginning from early 2003. This was later termed by the World Health Organisation as Severe Acute Respiratory Syndrome (SARS). The diagnosis of SARS relies on a combination of clinical features and chest radiographic findings. A preliminary review of SARS in Singapore shows chest radiographic findings of patchy airspace shadowing with severe cases progressing to diffuse air-space shadowing. We illustrate these findings with temporal correlation in our case report. As SARS is a contagious, rapidly progressive and potentially fatal condition, early diagnosis is crucial for prompt management and isolation of patients. Recognition of chest radiographic findings aids in the early diagnosis and containment of SARS.


title: [Clinical features of 77 patients with severe acute respiratory syndrome].

text: OBJECTIVE To analyze the clinical features of the severe acute respiratory syndrome (SARS) and the value for caring of patients suspected of having this disease. METHODS The data of the clinical presentations and course of disease in 77 epidemiologically linked patients (27 men and 50 women, 15 to 74 years old) in whom SARS was diagnosed after April 16, 2003 in Tianjin, China were summarized. RESULTS Exposure to ailing patients and occurrence of the disease ranged from minimal to close contact, such as between patient and health care personnel. The incubation period ranged from 1 to 11 days. All patients presented fever, and some of them complained of rigor, dry cough, dyspnea, malaise, headache, and hypoxemia. Physical examination of the chest revealed bubbling rales and dullness on percussion. Lymphopenia was observed in 80% of all patients, and some patients had mildly elevated aminotransferase levels but normal serum creatinine levels. Serial chest radiographs showed progressive inflammatory changes. One patient died of progressive respiratory failure; pathological examination of the lung showed diffuse alveolar damage. One patient died of suicide. There was no evidence of infection by Mycoplasma pneumoniae, Chlamydia pneumoniae, or Legionella pneumophila. All patients received corticosteroid and ribavirin therapy for a mean of (18.6+/-5.4) days after the onset of symptoms, and were treated with a combination of beta-lactams and macrolide early for (4.0+/-1.9)days, but with no clinical or radiologic evidences of improvement. CONCLUSION The combination treatment, especially including corticosteroid and ribavirn, is efficient.


Alcohol Policy and Coronavirus: An Open Research Agenda.


title: COVID-19 and pregnancy: a review of current knowledge.

text: BACKGROUND Since December 2019, coronavirus disease 2019 (COVID-19) has become a major health problem that is spreading all over the world. Several viral infections such as SARS, MERS, and influenza have been associated with adverse pregnancy outcomes. The question arises whether pregnant women are at greater risk of complications related to COVID-19 compared to other people What complications should we expect in the fetuses whose mothers were infected? AIMS This review aims to provide a summary of studies on symptoms of COVID-19 and the possible risks of COVID-19 among pregnant women, as well as complications in fetuses and neonates whose mothers were infected with COVID-19. METHODS The included data were provided from Web of Science, Cochrane, PubMed, and Scopus which are extracted from the published studies in English until April 2nd, 2020 that contained data on the risk of COVID-19 in pregnancy. RESULTS The early symptoms of patients with COVID-19 were fever, cough, dyspnea, myalgia, and fatigue; while production of sputum, headache, hemoptysis, and diarrhea were other symptoms which were less common. There is no evidence of vertical maternal-fetal transmission in pregnant women with COVID-19. CONCLUSIONS The clinical findings in pregnant women with COVID-19 are not significantly different compared to other patients, and pregnant women with COVID-19 are not at a higher risk of developing critical pneumonia compared to non-pregnant women. Although, there has been no sign of vertical infection in infants, but maternal infection can cause serious problems such as preterm labour and fetal distress.


Medicine's Challenges: Vaping and Coronavirus.


Suspected allergic reactions after vaccination in 85 dogs in Japan.


title: [Clinical analysis of complications after non- invasive positive pressure ventilation and an inquiry into the respiratory treatment strategy in patients with SARS].

text: OBJECTIVE To analyze the clinical data of severe acute respiratory syndrome (SARS) patients with pneumothorax and mediastinal emphysema occurring after the non-invasive positive pressure ventilation (NIPPV), and to inquire into relevant strategy in respiratory treatment in the SARS patients. METHODS Twenty-seven serious cases of SARS undergone NIPPV were analyzed retrospectively. RESULTS Pneumothorax and mediastinal emphysema occurred in 7 of 27 serious cases of SARS with NIPPV, and mediastinal emphysema occurred in 1 of 189 cases of SARS without mechanical ventilation (MV). The incidence of pneumothorax and mediastinal emphysema in serious cases of SARS with NIPPV was significantly higher (chi2=25.052, P<0.01) than that in cases of SARS without receiving MV. The peripheral blood oxygen saturation level was not changed significantly after reasonable adjustment of ventilation pressure and increase in oxygen concentration inhaled. Seven cases of pneumothorax and mediastinal emphysema improved gradually. CONCLUSION The incidence of pneumothorax and mediastinal emphysema in serious SARS patients with NIPPV is significantly higher than that in SARS patients without receiving MV. This might be related to SARS related pulmonary injuries, intensive cough and high mechanical ventilation pressure. The pneumothorax and mediastinal emphysema improve gradually in all cases after reasonable adjustment of mechanical ventilative pressure. So when NIPPV is used in the treatment of serious SARS patients to improve hypoxemia, optimized mechanical ventilative pressure should be acquired in order to avoid pneumothorax and mediastinal emphysema.


Lest we forget.


title: The avian reovirus genome segment S1 is a functionally tricistronic gene that expresses one structural and two nonstructural proteins in infected cells.

text: The avian reovirus S1 gene contains three partially overlapping, out-of-phase open reading frames (ORFs) that the highly conserved in all avian reovirus strains examined to date. The three S1 ORFs of the avian reovirus strain S1133 were individually expressed in bacterial cells, and their purified translation products used as antigens to raise specific polyclonal antibodies. With these antibodies we were able to demonstrate that all three S1 ORFs from different avian reovirus strains are translatable in infected cells. Proteins p10 and p17, which are specified by ORF1 and ORF2, respectively, are nonstructural proteins which associate with cell membranes, whereas ORF3 directs the synthesis of protein sigma C, a structural oligomeric protein responsible for cell attachment. While intracellular synthesis of protein sigma C was demonstrated a long time ago and that of protein p10 was reported recently, this is the first time that expression of the S1 ORF2 has been demonstrated experimentally. Thus, the previously reported coding capacity of the avian reovirus genome is now expanded to 14 proteins, of which ten are structural (lambda A, lambda B, lambda C, microA, microB, microBC, microBN, sigma A, sigma B, and sigma C) and four are nonstructural (microNS, sigma NS, p17, and p10). Finally, protein p10, but not p17 or sigma C, induces cell-cell fusion when transiently expressed in mammalian cells, supporting a previously published observation that the polypeptide encoded by the S1 ORF1 plays an important role in the syncytial phenotype displayed by avian reoviruses.


Canada insists that it is a safe place to visit.


Epidemic infections and their relevance to the Gulf and other Arabian Peninsula countries.


Overlapping agendas or serendipitous synergism.


title: Inhibition of Epstein-Barr virus replication by small interfering RNA targeting the Epstein-Barr virus protease gene.

text: BACKGROUND The Epstein-Barr virus (EBV) protease (PR), coded by the BVRF2 gene, is essential for the maturation of the viral capsid and viral DNA packaging during the late stage of the EBV lytic cycle. Like the other herpesvirus serine PRs, EBV PR could be a target for the inhibition of EBV replication. To date, no data have been reported on the inhibition of EBV PR messenger RNA (mRNA) by small interfering RNA (siRNA). METHODS In this study, siRNAs targeting EBV PR were delivered to the epithelial 293 cell line stably transfected with the complete B95-8 EBV episome. EBV DNA and PR mRNA were quantified by real-time PCR in cells and supernatant, protein expression was assessed by immunoblotting, and production of EBV infectious particles in the culture medium was measured by Raji cell superinfection. RESULTS The EBV PR mRNA within the cells was reduced by 73%, the PR protein by 35% and the amount of virus in the cell supernatant was drastically decreased by 86% or 95%, depending on the method. CONCLUSIONS The strong effect of the siRNA targeting EBV PR on EBV replication attests to the crucial role played by EBV PR in the production of infectious particles and suggests that targeting this enzyme can be a new strategy against EBV-associated diseases where virus replication occurs.


title: A review of the safety of favipiravir - a potential treatment in the COVID-19 pandemic?

text: Background Repurposing broad-spectrum antivirals is an immediate treatment opportunity for 2019 coronavirus disease (COVID-19). Favipiravir is an antiviral previously indicated for influenza and Ebola, which has shown some promise in early trials for treatment of COVID-19. We aim to review existing favipiravir safety evidence, which is vital to informing the potential future use of favipiravir in COVID-19. Methods A search was conducted across EMBASE and MEDLINE databases, supplemented by relevant grey-literature and ClinicalTrials.gov. All studies assessing the use of favipiravir in humans by 27 March 2020 were considered for inclusion. Further analysis of available safety data from phase 2 and 3 studies was undertaken. Data extracted were adverse events (AEs) grade 1-4, serious AEs and discontinuation for AEs. Specific AEs of interest highlighted in early-phase studies, including gastrointestinal AEs and hyperuricaemia, were also examined. Results Twenty-nine studies were identified as potential sources of evidence of the clinical safety of favipiravir. Six were phase 2 and 3 studies reporting relevant safety data for statistical comparison, representing a total of 4299 participants, an estimated 175 person-years-of-follow-up (PYFU). Comparator drugs were oseltamivir, umifenovir, lopinavir/ritonavir or placebo. Study follow-up was between 5 and 21 days. The proportions of grade 1-4 AEs on favipiravir was 28.2% vs 28.4% (P = n.s.) in the comparison arms. The proportion of discontinuations due to AEs on favipiravir was 1.1% vs 1.2% (P = n.s.) in the comparison arms. For serious AEs the proportion was 0.4% in both arms (P = n.s.). There were significantly fewer gastrointestinal AEs occurring on favipiravir vs comparators [8.7% vs 11.5%; P = 0.003]. Favipiravir showed significantly more uric acid elevations than comparators [5.8% vs 1.3%; P<0.0001]. Conclusions Favipiravir demonstrates a favourable safety profile regarding total and serious AEs. However, safety concerns remain: hyperuricaemia, teratogenicity and QTc prolongation have not yet been adequately studied. Favipiravir may be safe and tolerable in short-term use, but more evidence is needed to assess the longer-term effects of treatment. Given the limitations of the evidence and unresolved safety concerns, caution is warranted in the widespread use of favipiravir against pandemic COVID-19.


title: Community-acquired pneumonia: what is relevant and what is not?

text: PURPOSE OF REVIEW Community-acquired pneumonia is associated with significant morbidity and mortality and is the most common cause of death from infectious diseases in North America. The purpose of this review is to highlight recent advances in epidemiology, risk factors, severity criteria and antibiotic therapeutic regimens used for community-acquired pneumonia management. RECENT FINDINGS All guidelines recommend early and appropriate empiric therapy directed against common typical organisms, such as Streptococcus pneumoniae, and other atypical organisms, but clinicians should be aware of newer emerging pathogens such as community-acquired methicillin-resistant Staphylococcus aureus and Gram-negative pathogens. SUMMARY The optimum outcome in community-acquired pneumonia can be achieved by careful risk stratification using prediction rules together with appropriate antibiotic regimens. The mainstay of community-acquired pneumonia prevention is influenza and pneumococcal immunization. Promotion of smoking cessation will also help curtail the incidence of pneumococcal disease.


title: Meloxicam and surgical denervation of the coxofemoral joint for the treatment of degenerative osteoarthritis in a Bengal tiger (Panthera tigris tigris).

text: An adult male white Bengal tiger (Panthera tigris tigris) with pronounced atrophy of the pelvic musculature was diagnosed with degenerative osteoarthritis of the coxofemoral joints. Initial management with the nonsteroidal anti-inflammatory drug meloxicam and a semisynthetic sodium pentosan polysulfate resulted in clinical improvement and radiographic stabilization of the arthritic condition over several months. However, because pain was still evident, bilateral denervation of the coxofemoral joints was performed, successfully ameliorating the signs of osteoarthritic pain in the tiger. Meloxicam has shown good clinical efficacy for the treatment of osteoarthritis and other painful conditions in large felids. Coxofemoral joint denervation offers many advantages for the treatment of osteoarthritis in exotic carnivore species, and should be considered a viable treatment modality.


title: Children's vaccines do not induce cross reactivity against SARS-CoV.

text: In contrast with adults, children infected by severe acute respiratory syndrome-corona virus (SARS-CoV) develop milder clinical symptoms. Because of this, it is speculated that children vaccinated with various childhood vaccines might develop cross immunity against SARS-CoV. Antisera and T cells from mice immunised with various vaccines were used to determine whether they developed cross reactivity against SARS-CoV. The results showed no marked cross reactivity against SARS-CoV, which implies that the reduced symptoms among children infected by SARS-CoV may be caused by other factors.


Emerging opportunities to prevent occupational lung disease.


Airborne transmission of communicable infection--the elusive pathway.


title: Nuclear localization of flavivirus RNA synthesis in infected cells.

text: Flaviviral replication is believed to be exclusively cytoplasmic, occurring within virus-induced membrane-bound replication complexes in the host cytoplasm. Here we show that a significant proportion (20%) of the total RNA-dependent RNA polymerase (RdRp) activity from cells infected with West Nile virus, Japanese encephalitis virus (JEV), and dengue virus is resident within the nucleus. Consistent with this, the major replicase proteins NS3 and NS5 of JEV also localized within the nucleus. NS5 was found distributed throughout the nucleoplasm, but NS3 was present at sites of active flaviviral RNA synthesis, colocalizing with NS5, and visible as distinct foci along the inner periphery of the nucleus by confocal and immunoelectron microscopy. Both these viral replicase proteins were also present in the nuclear matrix, colocalizing with the peripheral lamina, and revealed a well-entrenched nuclear location for the viral replication complex. In keeping with this observation, antibodies to either NS3 or NS5 coimmunoprecipitated the other protein from isolated nuclei along with newly synthesized viral RNA. Taken together these data suggest an absolute requirement for both of the replicase proteins for nucleus-localized synthesis of flavivirus RNA. Thus, we conclusively demonstrate for the first time that the host cell nucleus functions as an additional site for the presence of functionally active flaviviral replicase complex.


title: Hematopoietic stem and progenitor cells: clinical and preclinical regeneration of the hematolymphoid system.

text: A vast literature exists on the biology of blood formation and regeneration under experimental and clinical conditions. The field of hematopoiesis was recently advanced by the capacity to purify to homogeneity primitive hematopoietic stem and progenitor cells. Isolation of cells at defined maturational stages has enhanced the understanding of the fundamental nature of stem cells, including how cell fate decisions are made, and this understanding is relevant to the development of other normal as well as malignant tissues. This review updates the basic biology of hematopoietic stem cells (HSC) and progenitors, the evolving use of purified HSC as grafts for clinical hematopoietic cell transplantation (HCT) including immune tolerance induction, and the application of HSC biology to other stem cell fields.


title: Simultaneous detection of influenza viruses A and B using real-time quantitative PCR.

text: Since influenza viruses can cause severe illness, timely diagnosis is important for an adequate intervention. The available rapid detection methods either lack sensitivity or require complex laboratory manipulation. This study describes a rapid, sensitive detection method that can be easily applied to routine diagnosis. This method simultaneously detects influenza viruses A and B in specimens of patients with respiratory infections using a TaqMan-based real-time PCR assay. Primers and probes were selected from highly conserved regions of the matrix protein gene of influenza virus A and the hemagglutinin gene segment of influenza virus B. The applicability of this multiplex PCR was evaluated with 27 influenza virus A and 9 influenza virus B reference strains and isolates. In addition, the specificity of the assay was assessed using eight reference strains of other respiratory viruses (parainfluenza viruses 1 to 3, respiratory syncytial virus Long strain, rhinoviruses 1A and 14, and coronaviruses OC43 and 229E) and 30 combined nose and throat swabs from asymptomatic subjects. Electron microscopy-counted stocks of influenza viruses A and B were used to develop a quantitative PCR format. Thirteen copies of viral RNA were detected for influenza virus A, and 11 copies were detected for influenza virus B, equaling 0.02 and 0.006 50% tissue culture infective doses, respectively. The diagnostic efficacy of the multiplex TaqMan-based PCR was determined by testing 98 clinical samples. This real-time PCR technique was found to be more sensitive than the combination of conventional viral culturing and shell vial culturing.


title: Identification of an ATPase activity associated with a 71-kilodalton polypeptide encoded in gene 1 of the human coronavirus 229E.

text: Human coronavirus 229E gene expression involves proteolytic processing of the gene 1-encoded polyproteins pp1a and pp1ab. In this study, we have detected a 71-kDa polypeptide in virus-infected cells that is released from pp1ab by the virus-encoded 3C-like proteinase and that has been predicted to contain both metal-binding and helicase domains. The polypeptide encompasses amino acids Ala-4996 to Gln-5592 of pp1ab and exhibits nucleic acid-stimulated ATPase activity when expressed as a fusion protein with the Escherichia coli maltose-binding protein. These data provide the first identification of a coronavirus open reading frame 1b-encoded enzymatic activity.


title: A new model for coronavirus transcription.

text: Coronaviruses contain an unusually long (27-32,000 ribonucleotide) positive sense RNA genome that is polyadenylated at the 3' end and capped at the 5' end. In addition to the genome, infected cells contain subgenomic mRNAs that form a 3' co-terminal nested set with the genome. In addition to their common 3' ends, the genome and the subgenomic mRNAs contain an identical 5' leader sequence. The transcription mechanism that coronaviruses use to produce subgenomic mRNA is not known and has been the subject of speculation since sequencing of the subgenomic mRNAs showed they must arise by discontinuous transcription. The current model called leader-primed transcription has subgenomic mRNAs transcribed directly from genome-length negative strands. It was based on the failure to find in coronavirus infected cells subgenome-length negative strands or replication intermediates containing subgenome-length negative strands. Clearly, these structures exist in infected cells and are transcriptionally active. We proposed a new model for coronavirus transcription which we called 3' discontinuous extension of negative strands. This model predicts that subgenome-length negative strands would be derived directly by transcription using the genome RNA as a template. The subgenome-length templates would contain the common 5' leader sequence and serve as templates for the production of subgenomic mRNAs. Our findings include showing that: 1. Replication intermediates (RIs) containing subgenome-length RNA exist in infected cells and are separable from RIs with genome-length templates. The RFs with subgenome-length templates are not derived by RNase treatment of RIs with genome-length templates. 2. The subgenome-length negative strands are formed early in infection when RIs are accumulating and the rate of viral RNA synthesis is increasing exponentially. 3. Subgenome-length negative strands contain at their 3' ends a complementary copy of the 72 nucleotide leader RNA that is found in the genome only at their 5' end. 4. RIs with subgenomic templates serve immediately as templates for transcription of subgenomic mRNAs. Because subgenomic mRNAs are not replicated, i.e., copied into negative strands that in turn are used as templates for subgenomic mRNA synthesis, we propose that the subgenome-length negative strands must arise directly by transcription of the genome and acquire their common 3' anti-leader sequence after polymerase jumping from the intergenic regions to the leader sequence at the 5' end of the genome. This would make negative strand synthesis discontinuous and subgenomic mRNA synthesis continuous, which is the opposite of what was proposed in the leader primed model.


title: Evaluation of immunomodulators, interferons and known in vitro SARS-coV inhibitors for inhibition of SARS-coV replication in BALB/c mice.

text: Compounds approved for therapeutic use and in vitro inhibitors of severe acute respiratory syndrome coronavirus (SARS-CoV) were evaluated for inhibition in the mouse SARS-CoV replication model. A hybrid interferon, interferon alpha (IFN-alpha) B/D, and a mismatched double-stranded (ds) RNA interferon (IFN) inducer, Ampligen (poly I:poly C124), were the only compounds that potently inhibited virus titres in the lungs of infected mice as assessed by CPE titration assays. When mice were dosed intraperitoneally (i.p.) with IFN-alpha B/D once daily for 3 days beginning 4 h after virus exposure, SARS-CoV replication in the lungs of infected mice was reduced by 1 log10 at 10,000 and 32,000 IU; at the highest dose of 100,000 IU, virus lung titres were below detectable limits. Ampligen used i.p. at 10 mg/kg 4 h prior to virus exposure also reduced virus lung titres to below detectable limits. Nelfinavir, beta-D-N4-hydroxycytidine, calpain inhibitor VI, 3-deazaneplanocin A and Alferon (human leukocyte IFN-alpha-n3) did not significantly reduce lung virus titres in mice. Anti-inflammatory agents, chloroquine, amodiaquin and pentoxifylline, were also inactive in vivo, suggesting that although they may be useful in ameliorating the hyperinflammatory response induced by the virus infection, they will not significantly reduce the replication of the virus, the inducer of inflammatory response. Thus, anti-inflammatory agents may only be useful in treating virus lung infections if used in combination with agents that inhibit virus replication. In summary, the data suggest that induction of IFN by mismatched dsRNA or actual treatment with exogenous IFN-alpha can inhibit SARS-CoV replication in the lungs of mice.


title: Identification of novel inhibitors of the SARS coronavirus main protease 3CLpro.

text: SARS (severe acute respiratory syndrome) is caused by a newly discovered coronavirus. A key enzyme for the maturation of this virus and, therefore, a target for drug development is the main protease 3CL(pro) (also termed SARS-CoV 3CL(pro)). We have cloned and expressed in Escherichia coli the full-length SARS-CoV 3CL(pro) as well as a truncated form containing only the catalytic domains. The recombinant proteins have been characterized enzymatically using a fluorescently labeled substrate; their structural stability in solution has been determined by differential scanning calorimetry, and novel inhibitors have been discovered. Expression of the catalytic region alone yields a protein with a reduced catalytic efficiency consistent with the proposed regulatory role of the alpha-helical domain. Differential scanning calorimetry indicates that the alpha-helical domain does not contribute to the structural stability of the catalytic domains. Analysis of the active site cavity reveals the presence of subsites that can be targeted with specific chemical functionalities. In particular, a cluster of serine residues (Ser139, Ser144, and Ser147) was identified near the active site cavity and was susceptible to being targeted by compounds containing boronic acid. This cluster is highly conserved in similar proteases from other coronaviruses, defining an attractive target for drug development. It was found that bifunctional aryl boronic acid compounds were particularly effective at inhibiting the protease, with inhibition constants as strong as 40 nM. Isothermal titration microcalorimetric experiments indicate that these inhibitors bind reversibly to 3CL(pro) in an enthalpically favorable fashion, implying that they establish strong interactions with the protease molecule, thus defining attractive molecular scaffolds for further optimization.


title: Polymorphisms in the mannose binding lectin-2 gene and acute respiratory distress syndrome.

text: OBJECTIVE The variant alleles in the mannose binding lectin-2 (MBL-2) gene have been associated with MBL deficiency and increased susceptibility to sepsis. We postulate that the variant MBL-2 genotypes are associated with increased susceptibility to and mortality in acute respiratory distress syndrome (ARDS). DESIGN Nested case-control study. SETTING Tertiary academic medical center. PATIENTS Two hundred and twelve Caucasians with ARDS and 442 controls genotyped for the variant X, D, B, and C alleles of codon -221, 52, 54, and 57, respectively. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Patients homozygous for the variant codon 54B allele (54BB) had worse severity of illness on admission (p = .007), greater likelihood of septic shock (p = .04), and increased odds of ARDS (adjusted odds ratio, 6.7; 95% confidence interval, 1.5-31) when compared with heterozygotes and homozygotes for the wild-type allele. This association with ARDS was especially strong among the 311 patients with septic shock (adjusted odds ratio, 12.0; 95% confidence interval, 1.9-74). Among the patients with ARDS, the 54BB genotype was associated with more daily organ dysfunction (p = .01) and higher mortality (adjusted hazard rate, 4.0; 95% confidence interval, 1.6-10). Development of ARDS and outcomes in ARDS did not vary significantly with variant alleles of codon -221, 52, and 57, but the power to detect an effect was limited secondary to the low allele frequencies. CONCLUSIONS The MBL-2 codon 54BB genotype may be important in ARDS susceptibility and outcome. Additional studies are needed to confirm these findings in other populations.


title: Comparison of Transumbilical Laparoscopically Assisted Appendectomy to Conventional Laparoscopic Appendectomy in Children.

text: PURPOSE To compare surgical outcomes of children with appendicitis treated with the transumbilical laparoscopically assisted appendectomy (TULAA) versus the conventional 3-port laparoscopic appendectomy (TPLA). MATERIALS AND METHODS Retrospective study of pediatric patients with appendicitis treated with TULAA or TPLA between January 2010 and December 2015. Operative time (OT), length of stay, cost, and surgical site infection rate were compared between the 2 groups. RESULTS Six hundred twenty-five appendectomies were performed [263 TULAA, 362 TPLA: acute (457), gangrenous (39), and perforated (129)]. TULAA had a shorter OT (median, 40 vs. 67 min; P<0.001), a shorter length of stay (median, 20 vs. 23 h; P<0.001), and a lesser cost (median $6266 vs. $8927; P<0.001). Surgical site infection rate was slightly higher in the TULAA group (6% vs. 4%; P=0.19). CONCLUSIONS TULAA had a shorter OT and was less costly than conventional TPLA. TULAA should be considered as the first surgical approach at treating appendicitis in children.


title: Frequency of puncture holes in peritoneal dialysis catheters related to the beta cap adapter.

text: Between November 2009 and September 2011, 12 patients (6 women, 6 men) undergoing continuous peritoneal dialysis (PD) or automated PD developed puncture-like holes in the PD catheter near the interface of the adapter with the superior aspect of the Silastic PD catheter The adapter is used to connect the PD catheter to the PD transfer set. Over the course of 23 months, the 12 patients presented to the PD unit with 19 separate instances of catheter holes, for an event rate of 0.23 holes per patient-year Data including socio-demographic information, PD modality, need for antibiotic treatment, event recurrence, infectious complications, and time from catheter placement were collected from patients whose catheters did and did not develop holes. We observed no differences between patients whose catheters developed holes and those whose catheters did not. The location of the individual holes suggested a relationship between the adapter and the catheter holes. The holes, which led to increased patient morbidity and costs, may be related to structural changes made in 2006 to the adapter.


Arenavirus gene structure and organization.


title: Direct comparison of a dietary portfolio of cholesterol-lowering foods with a statin in hypercholesterolemic participants.

text: BACKGROUND 3-Hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors reduce serum cholesterol and are increasingly advocated in primary prevention to achieve reductions in LDL cholesterol. Newer dietary approaches combining cholesterol-lowering foods may offer another option, but these approaches have not been compared directly with statins in the same persons. OBJECTIVE The objective was to compare, in the same subjects, the cholesterol-lowering potential of a dietary portfolio with that of a statin. DESIGN Thirty-four hyperlipidemic participants underwent all three 1-mo treatments in random order as outpatients: a very-low-saturated-fat diet (control diet), the same diet plus 20 mg lovastatin (statin diet), and a diet high in plant sterols (1.0 g/1000 kcal), soy-protein foods (including soy milks and soy burgers, 21.4 g/1000 kcal), almonds (14 g/1000 kcal), and viscous fibers from oats, barley, psyllium, and the vegetables okra and eggplant (10 g/1000 kcal) (portfolio diets). Fasting blood samples were obtained at 0, 2, and 4 wk. RESULTS LDL-cholesterol concentrations decreased by 8.5+/-1.9%, 33.3+/-1.9%, and 29.6+/-1.3% after 4 wk of the control, statin, and portfolio diets, respectively. Although the absolute difference between the statin and the portfolio treatments was significant at 4 wk (P=0.013), 9 participants (26%) achieved their lowest LDL-cholesterol concentrations with the portfolio diet. Moreover, the statin (n=27) and the portfolio (n=24) diets did not differ significantly (P=0.288) in their ability to reduce LDL cholesterol below the 3.4-mmol/L primary prevention cutoff. CONCLUSIONS Dietary combinations may not differ in potency from first-generation statins in achieving current lipid goals for primary prevention. They may, therefore, bridge the treatment gap between current therapeutic diets and newer statins.


title: Swine in biomedical research: creating the building blocks of animal models.

text: The opportunities for utilizing swine biomedical models are immense, particularly in models that address lifestyle issues (nutrition, stress, alcohol, drugs of abuse, etc.). However, in order to fully capitalize upon the promise, there needs to be a more general recognition of these cofactors, such as nutrition, as key modulators of phenotype via genomic, epigenetic, and postgenomic mechanisms. Furthermore, increased interactions between nutrition scientists and clinical and fundamental researchers in other disciplines, including developmental biology, immunology, neuroscience, oncology, and cardiovascular and gastrointestinal physiology, are required. Closing discussions focused on the need for future conferences at more frequent intervals to support interactions between the various disciplines. This was especially critical because of the global distribution of investigators.


title: Expression of matrix metalloproteinases and their tissue inhibitor during viral encephalitis.

text: Matrix metalloproteinases (MMPs) participate in remodeling the extracellular matrix and facilitate entry of inflammatory cells into tissues. Infection of the murine central nervous system (CNS) with a neurotropic coronavirus induces encephalitis associated with increased levels of mRNA encoding MMP-3 and MMP-12. Whereas virus-induced MMP-3 expression was restricted to CNS resident astrocytes, MMP-12 mRNA was expressed by both inflammatory cells and CNS resident cells. Immunosuppression increased both MMP-3 and MMP-12 mRNA levels in CNS resident cells, suggesting that the presence of virus rather than inflammation induced protease up-regulation. MMP activity is partially regulated by a small family of genes encoding tissue inhibitors of matrix metalloproteinases (TIMPs); among the TIMPs, only TIMP-1 mRNA expression increased in the CNS following coronavirus infection. During inflammation TIMP-1 mRNA was most prominently expressed by infiltrating cells. By contrast, in the immunosuppressed host TIMP-1 mRNA was expressed by CNS resident cells. Analysis of cytokine and chemokine mRNA induction within the infected CNS of healthy and immunocompromised mice suggested a possible correlation between increased viral replication and increased levels of beta interferon, MMP-3, MMP-12, and TIMP-1 mRNA. CD4+ T cells which localize to the perivascular and subarachnoid spaces were identified as the primary source of TIMP-1 protein. By contrast, protein expression was undetectable in astrocytes or CD8+ T cells, the primary antiviral effectors that localize to the CNS parenchyma in response to infection. These data suggest that in contrast to the results seen with MMPs, inhibition of protease activity via TIMP-1 expression correlates with the differential tissue distribution of T-cell subsets during acute coronavirus-induced encephalitis.


title: Giant porokeratosis.

text: Porokeratosis is a disorder of keratinization characterized by annular plaques with an atrophic center surrounded by a raised, keratotic wall. It has several clinical forms including a porokeratosis of Mibelli, giant porokeratosis, linear porokeratosis, disseminated superficial actinic porokeratosis, palmoplantar porokeratosis and punctate porokeratosis. We report a patient with the rare condition of giant porokeratosis. Several variants of porokeratosis coexist in our patient.


title: Effects of creating a non-specific, virus-hostile environment in the nasopharynx on symptoms and duration of common cold.

text: The Common Cold remains the most frequent symptomatic viral infection in man. Current best therapies are all symptomatic. New pharmacological therapies are likely to be prescription-bound, and as most Common Cold infections are successfully treated without the intervention of a Physician, there is a need for effective non-prescription therapy options. Aim of this study is to propose a new type of approach, based on the concept of making a hostile biological environment for virus survival and spreading at the point of infection, the nasopharynx. The hypothesis was advanced that infections could be controlled using a physical biological approach to create an environment at the point of infection, that is inhibitory to the survival, and persistence of infecting virus, and of viruses newly released from infected mucosal epithelial cells. A nasal irrigation spray, designed to deliver a low pH gel to the nasal cavity, was developed and tested in this study. The study was a randomised, parallel, double-blind, placebo-controlled evaluation of three formulations of irrigation nasal spray in 441 subjects. The objective was to test whether the formulations reduced Cold severity and Cold duration compared to a placebo nasal spray. Subjects were recruited, and supplied with the product when healthy, and were instructed to begin treating and recording symptom severity once they experienced the "first signs" of a Common Cold. To qualify, subjects had to volunteer that they had at least one of the symptoms: sore/scratchy throat, runny nose or congested nose. The product was used 4 times daily, with at least 4 hours separating each dose, for a maximum of 7 days. Efficacy was assessed by an Interactive Voice Recall System whereby subjects were required to contact the investigation site, by telephone, twice daily when they were asked to assess the severity of their symptoms using a four point ordinal scale where 0 = "absent", and 3 = "severe". The symptoms assessed were sore throat, runny nose, blocked nose, cough and tired/run-down feeling. Two formulations demonstrated significant effects. A hydroxy methyl propyl cellulose based formulation reduced symptom severity compared with placebo by 17% and a Poloxamer based formulation reduced severity by 21%. Duration of illness was reduced with a hydroxy methyl propyl cellulose based formulation by 1.5 days to 2.4 days (according to the dose) and by a Poloxamer based formulation by 2.5 days. Results of this study suggest that the creation of a non virus-specific, inhibitory environment in the nasopharynx holds promise as an effective method of controlling the severity and duration of the Common Cold.


title: Urinary tract infection (UTI) in newborns: risk factors, identification and prevention of consequences.

text: The aim of the study is identification of urinary tract infections (UTI) and urinary tract anomalies (UTA) already in the perinatal period. The authors attempted to prevent serious consequences of the above conditions in the examined children. Family history data, certain conditions in pregnancy and appertaining symptoms in children were elaborated to specify selective distinctive criteria for children at risk. Newborns (1200) were selected for potential existence of a UTI. All the examined newborns underwent a urinalysis. Those with significant bacteriuria were taken urine specimens, C-reactive protein (RVP), Complete Blood Count (CBC) and bilirubin. The newborns with a UTI and a suspected UTA were sent to ultrasound examination, direct radio nuclide cystography and Tc99m MAG3 dynamic scanning. The frequency of a UTI in the perinatal period amounted to 4.5%. A UTA was found in 29.6% of the examinees. The infection was more likely to appear among newborns with a UTA in their families, a UTI, pre-eclampsia and a febrile infection in mother, intrauterine growth retardation, premature rupture of membranes (RVP), umbilical cord strangulation, jaundice, cyanosis, breathing difficulties, seizures and asphyxia.


title: Berne virus is not 'coronavirus-like'.

text: In infected embryonic mule skin cells, Berne virus directs the synthesis of two main polypeptides (22K, 20K); in addition, virus-specific proteins with apparent molecular weights of greater than 200K, 80K to 120K, 32K and 17K were detected after radioimmune precipitation. The replication of Berne virus was reduced more than 1000-fold by actinomycin D, when the drug (0.1 to 1.0 micrograms/ml) was added during the first 8 h after infection; alpha-amanitin (25 micrograms/ml) produced a similar though less pronounced effect. U.v. preirradiation of the cells for greater than or equal to 5 s led to a dramatic decrease in the production of extracellular virus. The results presented support our suggestion that Berne virus is a representative of a new family of animal viruses.


title: Effect of intravenous immunoglobulin on prednisone dose in patients with pemphigus vulgaris.

text: BACKGROUND Current therapeutic options for the treatment of pemphigus vulgaris (PV) are prednisone and immunosuppressants. Patients unresponsive to high-dose systemic corticosteroids and conventional immunosuppressants may respond to intravenous immunoglobulin (IVIG). OBJECTIVE The primary outcome was the change in prednisone dose at 6 months and 1 year post-IVIG administration. METHODS A retrospective chart review of PV patients treated at Sunnybrook and Women's College Health Sciences Centre between January 1999 and October 2004 was conducted. Demographic information, corticosteroid and IVIG use, dosage, and the timing of administration for all patients were obtained. RESULTS Eight PV patients, mean age of 50 years (+/- 14.7 years), were reviewed. There was a significant decrease in mean prednisone dose at 6 months (45%) and 12 months (71%) compared with the mean dose at the start of treatment (p < .05). LIMITATIONS Concomitant medication use may influence results. CONCLUSION This study demonstrates that IVIG can lower prednisone doses in PV patients.


title: Human umbilical cord blood-derived stromal cells: multifaceted regulators of megakaryocytopoiesis.

text: It has been demonstrated that stromal cell precursors exist in human umbilical cord blood. After being cultured in vitro, these cells are called human umbilical cord blood-derived stromal cells (hUCBDSCs). However, the role of hUCBDSCs in hematopoiesis is still unclear. We have previously shown that hUCBDSCs are superior to human bone marrow stromal cells (hBMSCs) at enhancing the expansion of megakaryocyte colony forming units (CFU-Meg). Based on this observation, we postulated that hUCBDSCs might promote megakaryocytopoiesis. to test this hypothesis, we developed a megakaryocyte/hUCBDSC co-culture model and a hematopoietic microenvironment injury model in nude mice. We explored the ability and mechanisms by which hUCBDSCs promoted the proliferation of megakaryocytes in vitro, and we also explored their capacity to restore the hematopoietic microenvironment in vivo. As expected, hUCBDSCs were more efective than hBMSCs at enhancing the proliferation of megakaryocyte lines from HeL cells and restoring megakaryocytopoiesis in a hematopoietic microenvironment injury model in nude mice. thrombopoietin (tpo) and stromal cell derived factor-1 (SDF-1) are two of the key factors underlying this capacity. We also found that gap junction intercellular communication (GJIC) between HeL cells and hUCBDSCs might be partially absent. our data provide the first evidence that hUCBDSCs play a regulatory role during megakaryocytopoiesis, which might be important for designing treatments for patients with megakaryocytic injury.


title: Effects of an epitope-specific CD8+ T-cell response on murine coronavirus central nervous system disease: protection from virus replication and antigen spread and selection of epitope escape mutants.

text: Both CD4(+) and CD8(+) T cells are required for clearance of the murine coronavirus mouse hepatitis virus (MHV) during acute infection. We investigated the effects of an epitope-specific CD8(+) T-cell response on acute infection of MHV, strain A59, in the murine CNS. Mice with CD8(+) T cells specific for gp33-41 (an H-2D(b)-restricted CD8(+) T-cell epitope derived from lymphocytic choriomeningitis glycoprotein) were infected with a recombinant MHV-A59, also expressing gp33-41, as a fusion protein with enhanced green fluorescent protein (EGFP). By 5 days postinfection, these mice showed significantly (approximately 20-fold) lower titers of infectious virus in the brain compared to control mice. Furthermore mice with gp33-41-specific CD8(+) cells exhibited much reduced levels of viral antigen in the brain as measured by immunohistochemistry using an antibody directed against viral nucleocapsid. More than 90% of the viruses recovered from brain lysates of such protected mice, at 5 days postinfection, had lost the ability to express EGFP and had deletions in their genomes encompassing EGFP and gp33-41. In addition, genomes of viruses from about half the plaques that retained the EGFP gene had mutations within the gp33-41 epitope. On the other hand, gp33-41-specific cells failed to protect perforin-deficient mice from infection by the recombinant MHV expressing gp33, indicating that perforin-mediated mechanisms were needed. Virus recovered from perforin-deficient mice did not exhibit loss of EGFP expression and the gp33-41 epitope. These observations suggest that the cytotoxic T-cell response to gp33-41 exerts a strong immune pressure that quickly selects epitope escape mutants to gp33-41.


title: On board.

text: A&E sister Vicky Hamer was among emergency staff at Hope Hospital, Salford, who featured in a BBC One fly-onthe-wall documentary series, Trauma, this summer. Over the four weeks' filming staff came close to having to divert ambulances due to capacity problems and had to manage several suspected cases of severe acute respiratory syndrome (SARS). Ms Hamer said: 'It made us realise how well we worked together and it was good to reflect on that.'


title: Experimental infection of young rabbits with a rabbit enteric coronavirus.

text: The clinical signs and lesions caused by the rabbit enteric coronavirus (RECV) were studied in young rabbits orally inoculated with a suspension containing RECV particles. The inoculated animals were observed daily for evidence of diarrhea. Fecal samples and specimens from the small intestine and from the gut associated lymphoid tissue (GALT) were collected from 2 h to 29 days postinoculation (PI) and processed for immune electron microscopy (IEM) and light microscopy. Coronavirus particles were detected in the cecal contents of most inoculated animals from 6 h to 29 days PI. Lesions were first observed 6 h PI and were characterized by a loss of the brush border of mature enterocytes located at the tips of intestinal villi and by necrosis of these cells. At 48 h PI, short intestinal villi and hypertrophic crypts were noted. In the GALT, complete necrosis of the M cells as well as necrosis of the enterocytes lining the villi above the lymphoid follicules with hypertrophy of the corresponding crypts were observed in all the animals. Five inoculated rabbits had diarrhea three days PI. The presence of RECV particles in the feces of the sick animals and the microscopic lesions observed in the small intestine suggested that the virus was responsible for the clinical signs. A few inoculated rabbits remained free of diarrhea. Fecal material collected at postmortem examination contained RECV particles. The results suggest that the virus could also produce a subclinical infection.


title: Asthma fatalities at the Emergency Department of the Singapore General Hospital.

text: BACKGROUND Bronchial asthma is one of the most common chronic diseases in Singapore and the prevalence is increasing. Despite this, the worldwide mortality rate from asthma has been noted to be low at an average of 2.0 per 100,000 people in developed countries such as the United States. Risk factors for fatal asthma attacks that have been described include excessive use of short acting beta-agonists, errors in clinical judgement, poor compliance, psychosocial disorders, use of three or more groups of asthma medication and indicators of asthma severity. AIM We aim to study the incidence of asthma deaths occurring in the emergency department of a tertiary care hospital in Singapore. METHODS Of the total number of patients at the Department of Emergency Medicine in Singapore General Hospital from January 1999 to June 2005, eight fatalities were attributed to exacerbation of bronchial asthma. The characteristics of these patients are described. RESULTS A low incidence of asthma-related deaths is found in Singapore.


title: Infectious bronchitis virus S2 expressed from recombinant virus confers broad protection against challenge.

text: We developed a recombinant Newcastle disease virus (NDV) LaSota (rLS) expressing the infectious bronchitis virus (IBV) S2 gene (rLS/IBV.S2). The recombinant virus showed somewhat-reduced pathogenicity compared to the parental lentogenic LaSota strain but effectively elicited hemagglutination inhibition antibodies against NDV and protected chickens against lethal challenge with virulent NDV/CA02. IBV heterotypic protection was assessed using a prime-boost approach with a commercially available attenuated IBV Massachusetts (Mass)-type vaccine. Specific-pathogen-free chickens primed ocularly with rLS/IBV.S2 at 4 days of age and boosted with Mass at 18 days of age were completely protected against challenge at 41 days of age with a virulent Ark-type strain. In a second experiment, we compared protection conferred by priming with rLS/IBV.S2 and boosting with Mass (rLS/IBV.S2+Mass) versus priming and boosting with Mass (Mass+Mass). We also modified the timing of vaccination to prime at 1 day of age and boost at 12 days of age. Challenge with virulent Ark was performed at 21 days of age. Based on clinical signs, both vaccinated groups appeared equally protected against challenge compared to unvaccinated challenged chickens. Viral loads in lachrymal fluids of birds receiving rLS/IBV.S2+Mass showed a clear tendency of improved protection compared to Mass+Mass; however, the difference did not achieve statistical significance. A significant difference (P < 0.05) was determined between these groups regarding incidence of detection of challenge IBV RNA in the trachea; viral RNA was detected in 50% of rLS/IBV.S2+Mass-vaccinated chickens while chickens vaccinated with Mass+Mass and unvaccinated challenged controls showed 84 and 90% incidence of IBV RNA detection in the trachea, respectively. These results demonstrate that overexposing the IBV S2 to the chicken immune system by means of a vectored vaccine, followed by boost with whole virus, protects chickens against IBV showing dissimilar S1.


title: Rapid diagnostic assays in the genomic biology era: detection and identification of infectious disease and biological weapon agents.

text: In this special section of BioTechniques, we examine the role of rapid molecular technologies in the detection and identification of agents of infectious disease (ID) and biological weapons (BWs). Besides the threat posed by the global proliferation of BW technologies, there are numerous emerging and reemerging ID agents with significant public health consequences. Further compounding this already complicated situation are the estimated 600 million international tourists annually, many with the potential to the spread disease globally in a matter of hours. While clinical laboratories have key roles in the detection and identification of potential ID/BW agents, most staff are unfamiliar with these agents because of their rarity and the often laborious conventional methodologies needed to identify them. To meet this challenge, a vast array of rapid assay strategies has been developed for use in clinical diagnostics and environmental detection. Technologies have been developed or adapted to the challenges posed by these agents, permitting detection and identification in several minutes to hours. In particular, the development of improved reagents and detection systems has led to dramatic improvements in the sensitivity and specificity of immunological and nucleic acid-based systems, allowing an ever-increasing range of analytes to be identified and quantitated. In the accompanying articles, we have brought together experts from the many overlapping aspects of this arena in order to present a comprehensive and critical analysis of these technologies.


title: In situ hybridization: detecting viral nucleic acid in formalin-fixed, paraffin-embedded tissue samples.

text: In situ hybridization is a method for detecting specific nucleic acid sequences within individual cells. This technique permits visualization of viral nucleic acid or gene expression in individual cells within their histologic context. In situ hybridization is based on the complementary binding of a labeled nucleic acid probe to complementary sequences in cells or tissue sections, followed by visualization of target sequences within the cells. It has been used widely for the detection of viral nucleic acid sequences within individual cells. This review will define the technical approaches of in situ hybridization and its current application to detect viral nucleic acids within formalin-fixed, paraffin-embedded tissue samples, with special reference to the Epstein-Barr virus.


title: [Clinical features of severe acute respiratory syndrome in forty-one confirmed health care workers].

text: OBJECTIVE To investigate the clinical features of severe acute respiratory syndrome (SARS). METHODS Forty-one medical care workers (aged 23 - 55 years, with a average of 32 years; men/women = 8/32) who were admitted to our hospital and diagnosed with SARS during March and April, 2003 were retrospectively analyzed. RESULTS Thirteen of all the patients were physicians and the rest were nurses. The disease was mainly transmitted through air droplet in a short distance, and overwork induced tiredness was involved in disease stimulation. Seventy-three percent of the patients presented fever as their first symptom. Ten patients complained inertia and myalgia. One patient showed no clinical symptoms, and bilateral infiltrates was found in his chest X-ray. Among the 41 cases, 6 (15%) were diagnosed as severe type. At the first week, the counts of white blood cells (WBCs), lymphocyte and platelets were (4.4 +/- 1.5) x 10(9)/L, 0.22 +/- 0.12 and (143 +/- 37) x 10(9)/L, which were significantly lower when compared with those at the 2nd to 4th week. Abnormal liver function was found in 27 cases (mostly with elevated serum ALT), with 70% occurred at the 3rd or 4th week. In terms of CT, 30 patients (73%) showed pathological changes in lungs, and bilateral lung involvement was found in 35.59%. Of 36 cases treated with steroids, 86% received middle or low dosage (80 - 240 mg/d). Artificial ventilation was used for twenty-seven patients, and air pipe mechanical ventilation was used for 1 case. Mortality in this study was 5%. CONCLUSIONS Inertia and myalgia may be the earlier symptoms of health care workers with SARS include, which are parallel to CT manifestations. There is no objective index for the assessment of the severity of the disease at early stage. The medicine associated toxicities may be the main reason of liver lesions. damages. Middle or low dosage of steroid was reasonable to be used as early as possible.


title: Antigenic and molecular characterization of isolates of the Italy 02 infectious bronchitis virus genotype.

text: As part of an epidemiological surveillance of infectious bronchitis virus (IBV) in Spain, four Spanish field isolates showed high S1 spike sequence similarities with an IBV sequence from the GenBank database named Italy 02. Given that little was known about this new emergent IBV strain we have characterized the four isolates by sequencing the entire S1 part of the spike protein gene and have compared them with many reference IBV serotypes. In addition, cross-virus neutralization assays were conducted with the main IBV serotypes present in Europe. The four Spanish field strains and the Italy 02 S1 sequence from the NCBI database were established as a new genotype that showed maximum amino acid identities with the 4/91 serotype (81.7% to 83.7%), the D274 group that included D207, D274 and D3896 strains (79.8% to 81.7%), and the B1648 serotype (79.3% to 80%). Furthermore, on the basis of these results, it was demonstrated that the Italy 02 genotype had been circulating in Spain since as early as 1997. Based on the average ratio of synonymous:non-synonymous (dS/dN) amino acid substitutions within Italy 02 sequences, no positive selection pressures were related with changes observed in the S1 gene. Moreover, phylogenetic analysis of the S1 gene suggested that the Italy 02 genotype has undergone a recombination event. Virus neutralization assays demonstrated that little antigenic relatedness (less than 35%) exists between Italy 02 and some of the reference IBV serotypes, and indicated that Italy 02 is likely to be a new serotype.


title: The Economic Implications of COVID-19 in the United States.

text: The novel coronavirus disease 2019 (COVID-19) first reported in Wuhan, China, in 2019 has evolved into a pandemic and public health emergency, leading to extensive fatalities and halting global economies. Older adults have emerged as a critically vulnerable population as earlier data suggests a disproportionately increased incidence of COVID-19 in this population, as well as worse health outcomes. Disease attenuating behaviors such as social distancing has been encouraged and mandated across different countries leading to downstream economic ramifications. This paper seeks to outline the economic implications of COVID-19 in the U.S. (particularly in terms of vocational, retail, and service industries), highlighting the role of nursing homes in disease dissemination. We also discuss potential costs associated with COVID-19 management focusing on the senior population who rely on Medicare benefits for health insurance.


Traditional Chinese medicine--is the grass always greener?


Risk of high dose hydrocortisone in patients with aneurysmal subarachnoid hemorrhage.


title: Disease modifying treatment for feline rheumatoid arthritis.

text: Feline erosive polyarthritis includes the more common periosteal proliferative polyarthritis (PPP) and the rarely seen rheumatoid arthritis (RA) (11). During the past three years, 12 patients with definite feline rheumatoid arthritis, which did not respond well to conventional therapy, were treated with 7.5 mg of Methotrexate and 70 mg Leflunomide, given weekly by the oral route. The average age of the cats was 5.9 years (range 2.5 to 10 years). Siamese cats were over represented. Seven of the 12 (58%) cats showed a marked improvement, usually within four weeks. Once maximum improvement was obtained the dosage was decreased. Serious toxicity was not noted and carcinogenetic effect was not seen during the course of this study.


title: Adaptation of Borna disease virus to new host species attributed to altered regulation of viral polymerase activity.

text: Borna disease virus (BDV) can persistently infect the central nervous system of a broad range of mammalian species. Mice are resistant to infections with primary BDV isolates, but certain laboratory strains can be adapted to replicate in mice. We determined the molecular basis of adaptation by studying mutations acquired by a cDNA-derived BDV strain during one brain passage in rats and three passages in mice. The adapted virus propagated efficiently in mouse brains and induced neurological disease. Its genome contained seven point mutations, three of which caused amino acid changes in the L polymerase (L1116R and N1398D) and in the polymerase cofactor P (R66K). Recombinant BDV carrying these mutations either alone or in combination all showed enhanced multiplication speed in Vero cells, indicating improved intrinsic viral polymerase activity rather than adaptation to a mouse-specific factor. Mutations R66K and L1116R, but not N1398D, conferred replication competence of recombinant BDV in mice if introduced individually. Virus propagation in mouse brains was substantially enhanced if both L mutations were present simultaneously, but infection remained mostly nonsymptomatic. Only if all three amino acid substitutions were combined did BDV replicate vigorously and induce early disease in mice. Interestingly, the virulence-enhancing effect of the R66K mutation in P could be attributed to reduced negative regulation of polymerase activity by the viral X protein. Our data demonstrate that BDV replication competence in mice is mediated by the polymerase complex rather than the viral envelope and suggest that altered regulation of viral gene expression can favor adaptation to new host species.


title: An innovative paradigm for surgical education programs in resource-limited settings.

text: The burden of surgical disease in low-income countries remains significant, in part owing to continued surgical workforce shortages. We describe a successful paradigm to expand Rwandan surgical capacity through the implementation of a surgical education partnership between the National University of Rwanda and the Centre for Global Surgery at the McGill University Health Centre. Key considerations for such a program are highlighted.


title: Acceleration in the rate of CNS remyelination in lysolecithin-induced demyelination.

text: One important therapeutic goal during CNS injury from trauma or demyelinating diseases such as multiple sclerosis is to develop methods to promote remyelination. We tested the hypothesis that spontaneous remyelination in the toxic nonimmune model of lysolecithin-induced demyelination can be enhanced by manipulating the inflammatory response. In PBS-treated SJL/J mice, the number of remyelinating axons per square millimeter of lesion area increased significantly 3 and 5 weeks after lysolecithin injection in the spinal cord. However, methylprednisolone or a monoclonal antibody (mAb), SCH94.03, developed for its ability to promote remyelination in the Theiler's virus murine model of demyelination, further increased the number of remyelinating axons per lesion area at 3 weeks by a factor of 2.6 and 1.9, respectively, but did not increase the ratio of myelin sheath thickness to axon diameter or the number of cells incorporating tritiated thymidine in the lesion. After 3 weeks, the number of remyelinating axons in the methylprednisolone or mAb SCH94.03 treatment groups was similar to the spontaneous remyelination in the 5 week PBS control-treated group, indicating that these treatments promoted remyelination by increasing its rate rather than its extent. To address a mechanism for promoting remyelination, through an effect on scavenger function, we assessed morphometrically the number of macrophages in lesions after methylprednisolone and mAb SCH94.03 treatment. Methylprednisolone reduced the number of macrophages, but SCH94.03 did not, although both enhanced remyelination. This study supports the hypothesis that even in toxic nonprimary immune demyelination, manipulating the inflammatory response is a benefit in myelin repair.


Infectious diarrhea in children: Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.


title: Using conservation of pattern to estimate spatial parameters from a single snapshot.

text: Rapid reaction in the face of an epidemic is a key element in effective and efficient control; this is especially important when the disease has severe public health or economic consequences. Determining an appropriate level of response requires rapid estimation of the rate of spread of infection from limited disease distribution data. Generally, the techniques used to estimate such spatial parameters require detailed spatial data at multiple time points; such data are often time-consuming and expensive to collect. Here we present an alternative approach that is computationally efficient and only requires spatial data from a single time point, hence saving valuable time at the start of the epidemic. By assuming that fundamental spatial statistics are near equilibrium, parameters can be estimated by minimizing the expected rate of change of these statistics, hence conserving the general spatial pattern. Although applicable to both ecological and epidemiological data, here we focus on disease data from computer simulations and real epidemics to show that this method produces reliable results that could be used in practical situations.


Lessons in case management for the physician.


title: Bovine coronavirus genome.

text: The tissue culture-adapted strain (Mebus) of the bovine coronavirus was grown to titers of greater than 10(7) 50% tissue culture infective doses per ml in secondary bovine embryo kidney cells, and the RNA was isotopically labeled with [3H]uridine. The RNA was extracted from purified virus and was found to have the following properties. (i) It consisted primarily of a homogeneous large-molecular-weight species which comigrated electrophoretically with vesicular stomatitis viral RNA and therefore had an apparent molecular weight of 3.8 X 10(6). (ii) It remained as a 3.8 x 10(6)-molecular-weight molecule after heat denaturation when rapidly harvested virus was examined. (iii) It was 80% susceptible to pancreatic RNase A digestion in high (0.3 M) NaCl, and the 20% resistant fraction was 4S to 7S in size. (iv) It was polyadenylated to the extent that 40 and 60% of the native RNA bound to polyuridylic acid-Sepharose and oligodeoxythymidylic acid-cellulose, respectively, under conditions of high (0.5 M) NaCl.


title: Neutrophil degranulation and cell lysis is associated with clinical severity in virus-induced asthma.

text: Acute exacerbations of asthma are frequently caused by viral infections, but the inflammatory mechanisms in virus-induced asthma are poorly understood. The aim of the present study was to determine whether viral infection in acute asthma was associated with increased sputum neutrophil degranulation and increased cellular lysis and whether these changes are related to clinical severity. Adults (n=49) presenting to the emergency department with acute asthma were examined for infection by means of sputum direct-fluorescence antigen detection, sputum culture, and sputum polymerase chain reaction for Mycoplasma, Chlamydia and Legionella pneumophila, and all common respiratory viruses. Subjects infected with one of these agents were classed as having an infective exacerbation. Spirometry and sputum induction were performed on presentation and 4-5 weeks later. Thirty-seven subjects (76%) had virus infection and acute asthma. Those with virus infection had increased sputum neutrophils (p<0.05) and increased neutrophil elastase (p<0.05), this was related to increased elevated sputum lactate dehydrogenase (LDH). Subjects with noninfective asthma had an increase in the proportion of sputum eosinophils. Both groups had elevated sputum eosinophil cationic protein (ECP) concentrations. Higher levels of sputum LDH and ECP were associated with a longer hospital stay. Virus infection and acute asthma is associated with neutrophilic inflammation, cell lysis and more severe clinical disease.


Letter To The Editor - The Covid-19 Pandemic And Mental Health As Issues Considered Within The Context Of Adjustment Disorder And Psychosocial Interventions.


title: The future of health care in the United States.

text: The U.S. government is involved in health care in various ways that include (1) providing services to veterans, (2) paying for care received by Medicare and Medicaid beneficiaries, (3) assuring quality through regulatory activity, (4) financing the discovery of medical breakthroughs, and (5) training members of the health workforce and assuring that the nation has an adequate supply of them. With the aging of the population, the role of the government in these endeavors will increase. This essay considers ways in which the health care of tomorrow will be affected by the intermingling of factors such as demography, epidemiology, economics, technology, globalization, and individual health behavior.


title: Factors associated with transmission of severe acute respiratory syndrome among health-care workers in Singapore.

text: Between 1 and 22 March 2003, a nosocomial outbreak of Severe Acute Respiratory Syndrome (SARS) occurred at the Communicable Disease Centre in Tan Tock Seng Hospital, Singapore, the national treatment and isolation facility for patients with SARS. A case-control study with 36 cases and 50 controls was conducted of factors associated with the transmission of SARS within the hospital. In univariate analysis, contact with respiratory secretions elevated the odds ratio to 6.9 (95 % CI 1.4-34.6, P= 0.02). Protection was conferred by hand washing (OR 0.06, 95% CI 0.007-0.5, P=0.03) and wearing of N95 masks (OR 0.1, 95% CI 0.03-0.4, P=0.001). Use of gloves and gowns had no effect. Multivariate analysis confirmed the strong role of contact with respiratory secretions (adjusted OR 21.8, 95 % CI 1.7 274.8, P=0.017). Both hand washing (adjusted OR 0.07, 95 % CI 0.008-0.66, P=0.02) and wearing of N95 masks (adjusted OR 0.1, 95% CI 0.02-0.86, P=0.04) remained strongly protective but gowns and gloves had no effect.


title: Is there a case for a virus aetiology in multiple sclerosis?

text: Multiple Sclerosis (MS) is a devastating demyelinating disease with a very high prevalence in North-East Scotland and in the Orkney and Shetland Islands. MS appears to be a multifactorial disorder with environmental and genetic elements and it has been proposed that these, in tandem, provoke an autoimmune response giving rise to the disease. Although there is no direct evidence of a specific virus being involved in MS, there are nevertheless grounds for suspecting a viral association. This review discusses these aspects of MS and suggests that a more aggressive approach to unravelling the role of viruses is needed.