title: Symptomatic early neurosyphilis among HIV-positive men who have sex with men--four cities, United States, January 2002-June 2004.

text: Symptomatic early neurosyphilis is a rare manifestation of syphilis that usually occurs within the first 12 months of infection. Most neurologic symptoms of early neurosyphilis result from acute or subacute meningitis, abnormalities in cranial nerve function, and inflammatory vasculitis leading to a cerebrovascular accident. Symptomatic early neurosyphilis essentially disappeared in the United States after the introduction of penicillin treatment for syphilis in the late 1940s but reappeared in the 1980s among persons with human immunodeficiency virus (HIV) infection. The disease burden from neurosyphilis is unknown because national reporting of this disease is incomplete. Because the increase in syphilis cases during the past 5 years has occurred primarily among MSM, many of whom were infected with HIV, CDC conducted a review of possible neurosyphilis cases to describe the clinical course of symptomatic early neurosyphilis and to better characterize the risk for this illness among HIV-infected MSM. The review included health department records from four U.S. cities (Los Angeles, California; San Diego, California; Chicago, Illinois; and New York, New York) for the period January 2002-June 2004. This report describes the results of that review, which identified 49 HIV-positive MSM with symptomatic early neurosyphilis during that 30-month period. Among HIV-positive MSM with early syphilis, the estimated risk for having symptomatic early neurosyphilis was 1.7%, and the risk for having early neurosyphilis with persistent symptoms 6 months after treatment was 0.5%. These findings emphasize the importance of preventing syphilis in HIV-infected persons. HIV-infected persons with cranial nerve dysfunction or other unexplained neurologic symptoms should be evaluated for early neurosyphilis.


title: Requirements for brome mosaic virus subgenomic RNA synthesis in vivo and replicase-core promoter interactions in vitro.

text: Based solely on in vitro results, two contrasting models have been proposed for the recognition of the brome mosaic virus (BMV) subgenomic core promoter by the replicase. The first posits that the replicase recognizes at least four key nucleotides in the core promoter, followed by an induced fit, wherein some of the nucleotides base pair prior to the initiation of RNA synthesis (S. Adkins and C. C. Kao, Virology 252:1-8, 1998). The second model posits that a short RNA hairpin in the core promoter serves as a landing pad for the replicase and that at least some of the key nucleotides help form a stable hairpin (P. C. J. Haasnoot, F. Brederode, R. C. L. Olsthoorn, and J. Bol, RNA 6:708-716, 2000; P. C. J. Haasnoot, R. C. L. Olsthoorn, and J. Bol, RNA 8:110-122, 2002). We used transfected barley protoplasts to examine the recognition of the subgenomic core promoter by the BMV replicase. Key nucleotides required for subgenomic initiation in vitro were found to be important for RNA4 levels in protoplasts. In addition, additional residues not required in vitro and the formation of an RNA hairpin within the core promoter were correlated with wild-type RNA4 levels in cells. Using a template competition assay, the core promoter of ca. 20 nucleotides was found to be sufficient for replicase binding. Mutations of the key residues in the core promoter reduced replicase binding, but deletions that disrupt the predicted base pairing in the proposed stem retained binding at wild-type levels. Together, these results indicate that key nucleotides in the BMV subgenomic core promoter direct replicase recognition but that the formation of a stem-loop is required at a step after binding. Additional functional characterization of the subgenomic core promoter was performed. A portion of the promoter for BMV minus-strand RNA synthesis could substitute for the subgenomic core promoter in transfected cells. The comparable sequence from Cowpea Chlorotic Mottle Virus (CCMV) could also substitute for the BMV subgenomic core promoter. However, nucleotides in the CCMV core required for RNA synthesis are not identical to those in BMV, suggesting that the subgenomic core promoter can induce the BMV replicase in interactions needed for subgenomic RNA transcription in vivo.


title: Poliovirus 5'-terminal cloverleaf RNA is required in cis for VPg uridylylation and the initiation of negative-strand RNA synthesis.

text: Chimeric poliovirus RNAs, possessing the 5' nontranslated region (NTR) of hepatitis C virus in place of the 5' NTR of poliovirus, were used to examine the role of the poliovirus 5' NTR in viral replication. The chimeric viral RNAs were incubated in cell-free reaction mixtures capable of supporting the sequential translation and replication of poliovirus RNA. Using preinitiation RNA replication complexes formed in these reactions, we demonstrated that the 3' NTR of poliovirus RNA was insufficient, by itself, to recruit the viral replication proteins required for negative-strand RNA synthesis. The 5'-terminal cloverleaf of poliovirus RNA was required in cis to form functional preinitiation RNA replication complexes capable of uridylylating VPg and initiating the synthesis of negative-strand RNA. These results are consistent with a model in which the 5'-terminal cloverleaf and 3' NTRs of poliovirus RNA interact via temporally dynamic ribonucleoprotein complexes to coordinately mediate and regulate the sequential translation and replication of poliovirus RNA.


title: Developing a Simulation-Based Training Program for the Prehospital Professionals and Students on the Management of Middle East Respiratory Syndrome.

text: INTRODUCTION Middle East Respiratory Syndrome (MERS) is a major global health threat. Prehospital professionals face the risk of infection as they work to save lives. They should be made aware of the disease and be prepared to handle such cases. The aims of our study are to develop a training program about the prehospital management of a MERS case using standardized patient (SP) scenarios, to evaluate the awareness and preparedness of the participants about MERS, and to evaluate the effectiveness of this training. METHODS We developed 5 scenarios using SPs and an observation form. We included paramedic students and emergency medical service (EMS) providers in our study. They were involved in the simulations. RESULTS A total of 24 paramedic students and 33 EMS providers participated in our study. Sixteen (84%) of 19 teams recognized the possibility of MERS as a measure of their awareness in the baseline evaluation. The participants lacked donning and doffing personal protective equipments, which revealed their baseline level of preparedness for MERS. Certain improvements in donning and doffing personal protective equipment were observed in the posttraining evaluation. The participants provided positive feedback on the training program. CONCLUSIONS The training program was appropriate for both paramedic students and EMS providers. A positive educational climate was created. Because the main concerns of this study were awareness and preparedness, which required human interaction, the SP methodology was the optimal simulation modality.


title: [Computed tomography (CT) utility for diagnosis and triage during COVID-19 pandemic].

text: The nasopharyngeal smear with PCR analysis is the first diagnostic test proposed to confirm infection with COVID-19 SARS-CoV-2. However, its usefulness in emergency centers is limited due to its imperfect sensitivity (56-83 %), limited availability and the time required to obtain results. For this reason, the chest CT-scan has been proposed as a rapid triage tool for diagnosis in these suspect Covid-19 patients. However, its specificity is limited, exposing to the risk of over-diagnosis, and further data are needed to confirm its usefulness, and to highlight the possible prognostic value of the CT, in detecting early lesions associated with poor outcome, indicating the need for admission to intensive care.


title: Predictive models of control strategies involved in containing indoor airborne infections.

text: Recently developed control measure modeling approaches for containing airborne infections, including engineering controls with respiratory protection and public health interventions, are readily amenable to an integrated-scale analysis. Here we show that such models can be derived from an integrated-scale analysis generated from three different types of functional relationship: Wells-Riley mathematical model, competing-risks model, and Von Foerster equation, both of the key epidemiological determinants involved and of the functional connections between them. We examine mathematically the impact of engineering control measures such as enhanced air exchange and air filtration rates with personal masking combined with public health interventions such as vaccination, isolation, and contact tracing in containing the spread of indoor airborne infections including influenza, chickenpox, measles, and severe acute respiratory syndrome (SARS). If enhanced engineering controls could reduce the basic reproductive number (R0) below 1.60 for chickenpox and 3 for measles, our simulations show that in such a prepared response with public health interventions would have a high probability of containing the indoor airborne infections. Combinations of engineering control measures and public health interventions could moderately contain influenza strains with an R0 as high as 4. Our analysis indicates that effective isolation of symptomatic patients with low-efficacy contact tracing is sufficient to control a SARS outbreak. We suggest that a valuable added dimension to public health inventions could be provided by systematically quantifying transmissibility and proportion of asymptomatic infection of indoor airborne infection. Practical Implications We have developed a flexible mathematical model that can help determine the best intervention strategies for containing indoor airborne infections. The approach presented here is scalable and can be extended to include additional control efficacies. If a newly emergent airborne infection should appear, the model could be quickly calibrated to data and intervention options at the early stage of the outbreak. Data could be provided from the field to estimate value of R0, the serial interval between cases, the distributions of the latent, incubation, and infectious periods, case fatality rates, and secondary spread within important mixing groups. The combination of enhanced engineering control measures and assigned effective public health interventions would have a high probability for containing airborne infection.


title: Antiviral activity of eight commonly used medicinal plants in Taiwan.

text: In an effort to find new antiviral agents from natural products, hot water extracts of eight traditionally used medicinal plants in Taiwan were investigated in vitro for their activities against adenoviruses (ADV) and herpes simplex viruses (HSV). Results demonstrated that all extracts exhibited antiviral activity with different degrees of potency. Only two extracts were active in suppressing both HSV and ADV infections. Three extracts inhibited only ADV infection whereas one extract blocked only HSV infection. These results suggested that the aforementioned medicinal plants merit further investigation.


title: Inhibition of the growth of human coronavirus 229E by leupeptin.

text: The protease inhibitor leupeptin prevented multiplication of the human coronavirus strain 229E in cultures of MRC-C cells. The IC50 of leupeptin in plaque reduction tests was 0.4 micrograms/ml, whereas growth of host cells was unaffected by leupeptin at 50 micrograms/ml. Inhibition of plaque formation could be prevented by the addition of proteases to the overlay medium. In single-cycle growth experiments, leupeptin reduced virus yield only if added within 2 h of infection, indicating its action on an early stage of virus replication.


Risks of Infection among Laboratory Rats and Mice at Major Biomedical Research Institutions.


Serum antibodies to porcine circovirus type 1 and type 2 in pigs with and without PMWS.


title: Single clips versus multi-firing clip device for closure of mucosal incisions after peroral endoscopic myotomy (POEM).

text: Background and aims: After Peroral Endoscopic Myotomy (POEM), the mucosal incision is closed with endoscopically applied clips. After each clip placement, a subsequent clipping device has to be introduced through the working channel. With the Clipmaster3, three consecutive clips can be placed without reloading which could reduce closure time. We performed a prospective study evaluating efficacy, safety, and ease of use. Closure using Clipmaster3 was compared to closure with standard clips. Methods: Patients undergoing closure with the Clipmaster3 were compared to patients who underwent POEM with standard clip closure. Results: In total, 12 consecutive POEM closures with Clipmaster3 were compared to 24 standard POEM procedures. The Clipmaster3 and the standard group did not differ in sex distribution, age (42 years [29 - 49] vs 41 years [34 - 54] P = 0.379), achalasia subtype, disease duration, length of the mucosal incision (25.0 mm [20 - 30] vs 20.0 mm [20 - 30], P = 1.0), and closure time (622 seconds [438 - 909] vs 599 seconds [488 - 664] P = 0.72). Endoscopically successful closure could be performed in all patients. The proportion of all clips used that were either displaced or discarded was larger for Clipmaster3 (8.8 %) compared to standard closure (2.0 %, P = 0.00782). Ease of handling VAS (visual analogue scale) score for Clipmaster3 did not differ between endoscopist and endoscopy nurse (7 out of 10). Conclusions: Clipmaster3 is feasible and safe for closure of mucosal incisions after POEM. Clipmaster3 was not associated with reduced closure time. Compared to standard closure, more Clipmaster3 clips were displaced or discarded to achieve successful closure. A training effect cannot be excluded as a cause of these results. STUDY REGISTRATION NCT01405417.


title: Ecological change and the future of the human species: can physicians make a difference?

text: Global environmental change is occurring so rapidly that it is affecting the health and threatening the future of many of Earth's inhabitants, including human beings. Global warming; contamination of the air, water, and soil; and rampant deforestation have led to a collapse in biodiversity that threatens the integrity of the biophysical systems upon which all organisms depend.A basic cause of environmental degradation is human overpopulation and the nonsustainable consumption of natural resources by the human community. Everything that we have accomplished in the fields of medicine and public health could be undermined if we do not pay attention to these rapid environmental changes. As healers, human beings, and members of the biological community, we need to broaden our perspective on health and disease. Unless we devote our attention to stabilizing and repairing the ecosystem, our professional and personal accomplishments as health professionals may be swept away. Health care providers--particularly physicians--can play a role by adopting an ecosystem health perspective as we ply our trade. By helping people avoid unwanted pregnancies, by using resources parsimoniously, and by staying engaged in the natural world, we can help to prevent the collapse of the biological systems upon which we all depend.


title: Ubiquitin proteasome system as a pharmacological target in neurodegeneration.

text: Ubiquitinated protein aggregates are observed in the brains of Alzheimer's, Parkinson's and Huntington's disease patients and in other neurodegenerative disorders. These aggregates indicate that the ubiquitin proteasome system may be impaired in these diseases. To date no therapy is available that specifically targets this system, although preventing aggregate formation or stimulating the degradation of already formed aggregates by targeting components of the ubiquitin proteasome system is an attractive therapeutic approach. Here, we review the role of the ubiquitin proteasome system in aggregate formation with respect to neurodegenerative diseases, discussing the unfolded protein response, endoplasmic reticulum-associated degradation, aggresome formation and accumulation as well as aggregation and neurotoxicity of proteins involved in neurodegeneration. The potential of pharmacological intervention within this system in patients suffering from neurodegenerative diseases will be evaluated.


title: Worldwide risks of animal diseases: introduction.

text: Animal diseases impact food supplies, trade and commerce, and human health and well-being in every part of the world. Outbreaks draw the attention of those in agriculture, regulatory agencies, and government, as well as the general public. This was demonstrated by the 2000-2001 foot and mouth disease (FMD) outbreaks that occurred in Europe, South America, Asia and Africa and by the recent increased occurrence of emerging diseases transmitted from animals to humans. Examples of these emerging zoonotic diseases are highly pathogenic avian influenza, bovine spongiform encephalopathy, West Nile virus and severe acute respiratory syndrome. There is also the risk of well-known and preventable zoonotic diseases, such as rabies, brucellosis, leishmaniasis, and echinococcosis/hydatidosis, in certain countries; these diseases have a high morbidity with the potential for a very high mortality. Animal agriculturalists should have a global disease awareness of disease risks and develop plans of action to deal with them; in order to better respond to these diseases, they should develop the skills and competencies in politics, media interactions, and community engagement. This issue of Veterinaria Italiana presents information on the risk of animal diseases; their impact on animals and humans at the international, national, industry, and societal levels; and the responses to them. In addition, specific information is provided on national and international disease monitoring, surveillance and reporting, the risk of spread of disease by bioterrorism and on import risk analysis.


Teaching NeuroImages: Dynamic vertebral artery insufficiency.


title: [Humoral immunity indices of chronic alcoholism patients].

text: Sera obtained from 642 patients with chronic alcoholism and 400 sera from healthy donors, collected in different regions of the USSR (Moscow, the Kirghiz SSR, Transcarpathian Province, the northern Caucasus), were studied. Out of all patients with chronic alcoholism whose blood sera were examined, persons aged 20-30 years constituted 22%, 31-40 years, 41.8%, 41-50 years, 27.5%, above 50 years, 8.7%. The results of the study of the immune structure of these patients with respect to the causative agents of respiratory diseases revealed a large proportion of persons seropositive to influenza virus B Leningrad/369/75 (92-93%) and coronavirus OC-43 (78-93%). Patients with chronic alcoholism were shown to belong to a high risk group with respect to Legionella pneumophila infection. The proportion of persons with antibodies to L. pneumophila among such patients (up to 21.1%) was considerably higher than among healthy donors (not more than 6%). In different regions of the USSR large risk groups with respect to diphtheria (42-56%) and tetanus (12-45%) were detected among patients with chronic alcoholism. These patients also showed considerably higher levels of anti-tissue antibodies in comparison with the healthy population.


title: Reduction of acute respiratory illness (ARI) due to a voluntary workplace influenza vaccination program: who are more likely to get the benefit?

text: The study investigated the overall effectiveness and its determinants of an influenza vaccination in the reduction of acute respiratory illness (ARI) clinic visits and sickness absence for a working population. We collected and compared the data of clinic visits and hours of sick leave among vaccinated and non-vaccinated workers during January and April in 1998 and 1999. A multiple regression analysis was conducted to explore possible determinants. The incidence rate of ARI clinic visits dropped 37.9% in 1999, with 57.3% reduction in vaccinated and 14.1% in un-vaccinated workers. Multiple regression analysis showed that the reduction was significantly associated with vaccination status, a history of diabetes, and occurrence of ARI clinic visits in 1998. Influenza vaccination is effective in reducing ARI clinic visits and sickness absence. Workers with a previous history of ARI, diabetes, and possibly young workers living with children were more likely to get the benefit. The identification of potential susceptible subpopulations can also minimize confusion on company policy for isolation during an epidemic of new infectious disease with flu-like symptoms.


title: SARS-CoV virus-host interactions and comparative etiologies of acute respiratory distress syndrome as determined by transcriptional and cytokine profiling of formalin-fixed paraffin-embedded tissues.

text: These studies attempt to understand more fully the host response and pathogenesis associated with severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) by monitoring gene expression using formalin-fixed paraffin-embedded (FFPE) pulmonary autopsy tissues. These tissues were from patients in different hospitals in Singapore who were diagnosed with various microbial infections, including SARS-CoV, that caused acute respiratory distress syndrome (ARDS). Global expression patterns showed limited correlation between end-stage ARDS and the initiating pathogen, but when focusing on a subset of genes implicated in pulmonary pathogenesis, molecular signatures of pulmonary disease were obtained and appeared to be influenced by preexisting pulmonary complications and also bacterial components of infection. Many factors detected during pulmonary damage and repair, such as extracellular matrix (ECM) components, transforming growth factor (TGF) enhancers, acute-phase proteins, and antioxidants, were included in the molecular profiles of these ARDS lung tissues. In addition, differential expression of cytokines within these pulmonary tissues were observed, including notable genes involved in the interferon (IFN) pathway, such as Stat1, IFN regulatory factor-1 (IRF-1), interleukin-6 (IL-6), IL-8, and IL-18, that are often characterized as elevated in ARDS patients.


Barking up the wrong tree: the FDA's misguided attempt to waive informed consent in public health emergencies.


title: Operative techniques in early-stage lung cancer.

text: Lung cancer is the most common cause of death by malignancy, responsible for more deaths than the next 4 causes combined and predicted to account for nearly 220,000 new cancer diagnoses and 160,000 deaths in 2009. The cornerstone of therapy for early-stage lung cancer is lobectomy and mediastinal lymph node dissection. Although lobectomy is considered the standard procedure, segmentectomy may be appropriate for selected patients. Conventional approaches to resection may be used, including posterolateral and muscle-sparing thoracotomy. However, minimally invasive lobectomy and segmentectomy procedures are now commonly used with superior outcomes.


title: Mapping of antigenic sites on the nucleocapsid protein of the severe acute respiratory syndrome coronavirus.

text: Antigenic sites on the nucleocapsid (N) protein of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) were mapped by Pepscan analysis with overlapping peptides that span the N protein sequence. Two major immunodominant epitopes located in the C-terminal region (amino acids [aa] 362 to 412) and middle region (aa 153 to 178) reacted with more than 75% of sera from SARS patients. Several minor immunodominant epitopes were reactive with about 50% of the SARS sera. Antisera from mice immunized with inactivated SARS-CoV recognized the two major immunodominant epitopes and one antigenic site located adjacent to the N-terminal region (aa 76 to 101), which did not react with the sera from SARS patients. Several monoclonal antibodies against SARS-CoV bound to the N- or C-terminal antigenic sites. These results suggest that the above antigenic sites on the N protein are important in eliciting humoral immune response against SARS-CoV in humans and animals and can be used as antigens for developing diagnostic tests.


title: Demyelination induced by murine coronavirus JHM infection of congenitally immunodeficient mice.

text: Mouse hepatitis virus JHM (JHMV or MHV-4) induces demyelination in rodents and has been studied as a model for the human disease, multiple sclerosis (MS). As is proposed in MS, the mechanism of subacute demyelination induced by JHMV appears to be primarily immunopathological, since demyelination in JHMV-infected mice is abrogated by immunosuppressive doses of irradiation and restored by adoptive transfer of splenocytes. Thy-1+ cells play a critical role in transmitting disease to these recipient mice. To further characterize cells which may mediate JHMV-induced immunopathology, we inoculated congenitally immunodeficient mice with JHMV. By 12 days post-inoculation, both immunocompetent C57BL/6J controls and athymic nude C57BL/6 mice had severe paralysis and demyelination. In marked contrast, C57BL/6 mice with the severe combined immune deficiency (SCID) mutation had little or no paralysis or demyelination. Adoptive transfer of immune spleen cells from nude mice to infected SCID mice produced paralysis and demyelination. These findings suggest that a cell population present in immunocompetent C57BL/6J and nude mice but absent or non-functional in irradiated and SCID mice is essential for JHMV-induced demyelination. Identification of cells which mediate demyelination in this experimental system may have implications for our understanding of coronavirus pathogenesis and human demyelinating diseases.


title: The effect of laparoscopic surgery in stage II and III right-sided colon cancer: a retrospective study.

text: BACKGROUND This retrospective study compared the clinicopathological results among three groups divided by time sequence to evaluate the impact of introducing laparoscopic surgery on long-term oncological outcomes for right-sided colon cancer. METHODS From April 1986 to December 2006, 200 patients who underwent elective surgery with stage II and III right-sided colon cancer were analyzed. The period for group I referred back to the time when laparoscopic approach had not yet been introduced. The period for group II was designated as the time when first laparoscopic approach for right colectomy was carried out until we overcame its learning curve. The period for group III was the period after overcoming this learning curve. RESULTS When groups I and II, and groups II and III were compared, overall survival (OS) did not differ significantly whereas disease-free survival (DFS) in groups I and III were statistically higher than in group II (P = 0.042 and P = 0.050). In group III, laparoscopic surgery had a tendency to provide better long-term OS ( P = 0.2036) and DFS ( P = 0.2356) than open surgery. Also, the incidence of local recurrence in group III (2.6%) was significantly lower than that in groups II (7.4%) and I (12.1%) ( P = 0.013). CONCLUSIONS Institutions should standardize their techniques and then provide fellowship training for newcomers of laparoscopic colon cancer surgery. This technique once mastered will become the gold standard approach to colon surgery as it is both safe and feasible considering the oncological and technical aspects.


Monkeypox, Marshfield Clinic and the Internet: leveraging information technology for public health.


title: New approaches to rapidly control foot-and-mouth disease outbreaks.

text: Economically, foot-and-mouth disease is the most important viral-induced livestock disease worldwide. The disease is highly contagious and foot-and-mouth disease virus replicates and spreads extremely rapidly. Recent outbreaks in previously foot-and-mouth disease-free countries and the potential use of foot-and-mouth disease virus by terrorist groups have demonstrated the vulnerability of countries and the need to develop control strategies that can rapidly inhibit or limit spread of the disease. The current vaccine, an inactivated whole-virus preparation, has a number of limitations for use in outbreaks in disease-free countries. This review discusses the potential of the antiviral agent, Type I interferon, to produce rapid protection and proposes a combination strategy of an antiviral agent and a foot-and-mouth disease vaccine to induce both immediate and long-lasting protective responses.


title: Effect of perceptions of menstrual blood loss and menstrual pain on women's quality of life.

text: OBJECTIVES The aim of the study was to explore Australian women's experiences of menstruation and effect on quality of life (QoL). METHODS A representative sample of women recruited through a commercial social research sampling organisation completed a detailed online questionnaire about menstruation. Specific detailed questions were asked about perceptions of heavy menstrual bleeding (HMB) and menstrual pain. RESULTS The questionnaire was completed by 1575 women aged 20-39 years. Most perceived their bleeding to be light (11.6%) or moderate (60.5%); 363 (22.5%) perceived it to be heavy and 86 (5.3%) very heavy. Women who experienced severe or very severe menstrual pain were significantly more likely to report periods as heavy or very heavy (p < .001). The prevalence ratios for being confined to bed during menstruation for women experiencing severe or very severe menstrual pain were 12.02 (95% CI: 5.71-25.31) and 15.93 (95% CI: 7.51-33.78), respectively, compared with women experiencing no pain. The prevalence ratios for being confined to bed were 1.58 (95% CI: 1.11-2.24) and 1.53 (95% CI: 1.04-2.25) for women with heavy or very heavy bleeding, respectively. Women who experienced severe or very severe menstrual pain associated with their HMB were >12 times more likely to be confined to bed for 0.5-1 day during menstruation than if they reported HMB without pain. CONCLUSION Severe menstrual pain with HMB has a much more profound effect on all aspects of women's QoL than HMB alone; it accounts for more days in bed and for loss of productivity.


title: The "temporary caging" technique for catheter navigation in patients with intracranial wide-necked aneurysms.

text: Endovascular treatment of wide-necked aneurysms with preservation of the parent artery remains a challenge. The authors describe a novel and simple technique to navigate a balloon or stent-delivery catheter across a wide-necked aneurysm in which previously existing methods could have failed to pass the catheter across the neck of the aneurysm, which we have named "temporary caging" technique. The technical results using this method are presented in 6 cases.


title: Further characterization of aminopeptidase-N as a receptor for coronaviruses.

text: We recently reported that porcine aminopeptidase-N (pAPN) acts as a receptor for transmissible gastroenteritis virus (TGEV). In the present work, we addressed the question of whether TGEV tropism is determined only by the virus-receptor interaction. To this end, different non-permissive cell lines were transfected with the porcine APN cDNA and tested for their susceptibility to TGEV infection. The four transfected cell lines shown to express pAPN at their membrane became sensitive to infection. Two of these cell lines were found to be defective for the production of viral particles. This suggests that other factor(s) than pAPN expression may be involved in the production of infectious virions. The pAPN-transfected cells were also tested for their susceptibility to several viruses which have a close antigenic relationship to TGEV. So far, we failed to evidence permissivity to the feline infectious peritonitis coronavirus FIPV and canine coronavirus CCV. In contrast, we found clear evidence that porcine respiratory coronavirus PRCV, a variant of TGEV which replicates efficiently in the respiratory tract but to a very low extent in the gut, may also utilise APN to gain entry into the host cells. This suggests that the switch between TGEV and PRCV tropisms in vivo may involve other determinant(s) than receptor recognition.


title: [Prospective 2-year clinical study of patients with positive IgG-antibodies after recovering from severe acute respiratory syndrome].

text: OBJECTIVE To investigate the clinical characteristics of patients recovering from severe acute respiratory syndrome (SARS) during 2 years after the infection. METHODS The antibody of SARS-IgG, T cell subsets, chest CT, and the pulmonary function were observed in patients 1 month, 3 months, 6 months, and 2 years after convalescence from SARS. RESULTS In the 20 SARS cases, the level of antibodies was found to descend gradually and slowly during 2 years after convalescence. In the majority of patients T cell subsets recovered completely to normal range at the second examination. At the first re-examination, the rate of abnormal chest CT was 65%, and the main abnormal images included ground glass opacities, thickening of inter-lobular and intra-lobular septa, distorted lobular structure, thickened bronchovascular bundles, thickened pleura, arc shadow under the pleura, bronchiolar dilation, and honey comb like shadows. The rate of abnormal chest CT was 30% at the 4 fourth examination. At the first re-examination, the abnormal rate of KCO was highest, accompanied by abnormalities of forced expiratory volume in 1 second (FEV1) and the diffusing capacity of the lung for carbon monoxide (DLCO), and it began to recover since the third examination. CONCLUSION The level of SARS-IgG descends slowly, and it may last for a long time. The recovery of chest CT to normal may take a long time. The abnormality in pulmonary functions manifests mainly as impairment of diffusion function. Further research on SARS is necessary.


title: Management of distal posterior inferior cerebellar artery aneurysms.

text: BACKGROUND Most of the posterior inferior cerebellar artery (PICA) aneurysms arise at the vertebral artery-PICA junction; distal PICA aneurysms are rare. Their clinical features and treatments are not fully understood. METHODS This was a retrospective study. We reported 9 patients with the distal PICA aneurysms treated by surgical clipping or endovascular embolization in our neurosurgical center. RESULTS All patients experienced sudden onset of headache with subarachnoid hemorrhage. The location of PICA aneurysms was at the anterior-medullary (n = 4), tonsillomedullary (TM) (n = 1), and telovelotonsillar (n = 4). Surgical clipping was performed in 3 and endovascular coil in 6 patients. All the PICA aneurysms were occluded with parent artery preservation, and all of the patients achieved good recovery. CONCLUSIONS Distal PICA aneurysm is exceptionally rare; it could be treated successfully with surgical clipping or endovascular treatments.


title: Usefulness of central venous oxygen saturation monitoring during bidirectional Glenn shunt.

text: A PediaSat™ oximetry catheter (PediaSat: Edwards Lifesciences Co., Ltd., Irvine, CA, U. S. A.), which facilitates continuous measurement of central venous oxygen saturation (ScvO2), may be useful for surgery for pediatric congenital heart disease. We used PediaSat during a bidirectional Glenn shunt. The patient was a 13-month-old boy. Under a diagnosis of left single ventricle (pulmonary atresia, right ventricular hypoplasia, atrial septal defect) and residual left aortic arch/left superior vena cava, a modified right Blalock-Taussig shunt was performed. Cyanosis deteriorated, so a bidirectional Glenn shunt was scheduled. After anesthesia induction, a 4.5 Fr double-lumen (8 cm) PediaSat was inserted through the right internal jugular vein for continuous ScvO2 monitoring. Furthermore, the probe of a near-infrared, mixed blood oxygen saturation-measuring monitor was attached to the forehead for continuous monitoring of the regional brain tissue mixed blood oxygen saturation (rSO2) (INVOS™ 5100C, Covidien; Boulder, CO, U. S. A.). Blockage of the right pulmonary artery and right superior vena cava decreased the oxygen saturation, ScvO2, and rSO2, but increased the central venous pressure. Although changes in ScvO2 were parallel to those in rSO2, the former showed more marked changes. A combination of ScvO2 and rSO2 for monitoring during Glenn shunt may be safer.


title: Comparative examination of cats with feline leukemia virus-associated enteritis and other relevant forms of feline enteritis.

text: Cats with feline leukemia virus (FeLV)-associated enteritis (FAE), enteritis of other known viral etiology (parvovirus [PV], enteric coronavirus [CoV]), and enteritis of unknown etiology with histologic features similar to those of FAE and PV enteritis (EUE) and FeLV-negative and FeLV-positive cats without enterocyte alterations were examined. Amount and types of infiltrating leukocytes in the jejunum and activity and cellular constituents of mesenteric lymph nodes, spleen, and bone marrow were determined. PV and CoV infections were confirmed by immunohistologic demonstration of PV and CoV antigen, ultrastructural demonstration of viral particles in the intestinal content, and in situ hybridization for PV genome. FeLV infection was detected by immunohistology for gp70, p27, and p15E. Latent FeLV infection was excluded by polymerase chain reaction methods for exogenous FeLV DNA. Enterocyte lesions involved the crypts in cats with PV enteritis, FAE, and EUE and the villous tips in cats with CoV enteritis. Inflammatory infiltration was generally dominated by mononuclear cells and was moderate in the unaltered intestine and in cats with PV enteritis and marked in cats with FAE, CoV enteritis, and EUE. In cats with EUE, myeloid/histiocyte antigen-positive macrophages were relatively numerous, suggesting recruitment of peripheral blood monocytes. Lymphoid tissues were depleted in cats with PV enteritis and with EUE but were normal or hyperplastic in cats with FAE. Bone marrow activity was decreased in cats with PV enteritis; in cats with FAE or EUE and in FeLV-positive cats without enterocyte alterations, activity was slightly increased. In cats with FAE and PV enteritis, a T-cell-dominated response prevailed. EUE showed some parallels to human inflammatory bowel disease, indicating a potential harmful effect of infiltrating macrophages on the intestinal epithelium.


In vivo and in vitro models of demyelinating disease, XXI: relationship between differentiation of rat oligodendrocytes and control of JHMV replication.


title: Assessment of determinants affecting the dual topology of hepadnaviral large envelope proteins.

text: For functional diversity, the large (L) envelope protein of hepatitis B virus (HBV) acquires a dual transmembrane topology via co-translational membrane integration of the S region and partial post-translational translocation of the preS subdomain. Because each process requires the second transmembrane segment (TM2), we explored the action of this determinant by using protease protection analysis of mutant L proteins. We demonstrated that neither the disruption of a leucine zipper-like motif by multiple alanine substitutions nor the flanking charges of TM2 affected the topological reorientation of L. The dispensability of both putative subunit interaction modules argues against a link between preS post-translocation and envelope assembly. Phenotypic mixing experiments revealed that the preS and S protein domains of the related duck HBV L polypeptide failed to substitute functionally for the topogenic elements of HBV in directing the correct L topogenesis, implicating different translocation mechanisms used by the two hepadnavirus genera.


title: How to read a review paper.

text: Review papers commonly summarize the current knowledge on a selected topic. These types of papers are considered narrative reviews. Narrative reviews rarely detail the methods used to select the literature included, nor do the authors typically report the purpose of the review. Narrative reviews may be biased due to inadequate literature reviews or individual beliefs. A systematic review limits bias by disclosing the purpose of the paper, the assembly of the literature, and the appraisal of study quality. A meta-analysis, a specific style of systematic review, quantitatively pools data from individual studies for re-analysis. Pooling data increases the sample size and improves statistical power. The common representation of a meta-analysis is the forest plot. The forest plot demonstrates the odds ratio of individual studies, the weight each trial contributes to the analysis, and the 95% confidence intervals. Systematic reviews and meta-analyses are not without shortcomings, including issues related to study heterogeneity. Because of their transparency, systematic evaluations of the literature are superior to narrative reviews.


title: Diagnostic testing.

text: The results of cardiac tests must always be interpreted through the lens of pretest probabilities created by the history and the physical examination. Tests should be chosen with a clear diagnostic and prognostic purpose in mind. A clear understanding of the relationship between the history and physical examination and more technologic diagnostic testing improves the primary care physician's ability to evaluate potential cardiac disease in an efficient and cost-effective manner.


Temperature-sensitive mutants of MHV-A59.


title: [COVID-19: care at home or in hospital? Considerations in primary care].

text: COVID-19 is a treacherous disease, in which infected patients who appear to fare well can deteriorate rapidly, mostly due to respiratory failure. For general practitioners (and other first-line responders), a clinical evaluation at any given time merely provides a snapshot of the patient's condition. Therefore, frequent monitoring is warranted in at-risk patients. However, there is no one-size-fits-all approach for monitoring, treatment and referral decisions. This is particularly the case in patients with advanced age. In this article, through the use of case examples, we aim to provide guidance when facing difficult management decisions in patients with (suspected) COVID-19.


title: The missing link in coronavirus assembly. Retention of the avian coronavirus infectious bronchitis virus envelope protein in the pre-Golgi compartments and physical interaction between the envelope and membrane proteins.

text: One missing link in the coronavirus assembly is the physical interaction between two crucial structural proteins, the membrane (M) and envelope (E) proteins. In this study, we demonstrate that the coronavirus infectious bronchitis virus E can physically interact, via a putative peripheral domain, with M. Deletion of this domain resulted in a drastic reduction in the incorporation of M into virus-like particles. Immunofluorescent staining of cells coexpressing M and E supports that E interacts with M and relocates M to the same subcellular compartments that E resides in. E was retained in the pre-Golgi membranes, prior to being translocated to the Golgi apparatus and the secretory vesicles; M was observed to exhibit similar localization and translocation profiles as E when coexpressed with E. Deletion studies identified the C-terminal 6-residue RDKLYS as the endoplasmic reticulum retention signal of E, and site-directed mutagenesis of the -4 lysine residue to glutamine resulted in the accumulation of E in the Golgi apparatus. The third domain of E that plays a crucial role in virus budding is a putative transmembrane domain present at the N-terminal region, because deletion of the domain resulted in a free distribution of the mutant protein and in dysfunctional viral assembly.


title: Influenza vaccination coverage among pregnant women - 29 States and New York City, 2009-10 season.

text: Because influenza can be especially severe during pregnancy, the American College of Obstetricians and Gynecologists (ACOG) and the Advisory Committee on Immunization Practices (ACIP) recommend influenza vaccination for women who will be pregnant during the influenza season, regardless of trimester. During the 2009-10 influenza season, pregnant women were at increased risk for severe disease and mortality from influenza A (H1N1)pdm09 (pH1N1) pandemic virus infection. Anticipating this risk, both the inactivated trivalent seasonal and monovalent pH1N1 vaccinations were recommended for pregnant women. To estimate state-specific seasonal and pH1N1 influenza vaccination coverage among pregnant women, CDC analyzed data from the Pregnancy Risk Assessment Monitoring System (PRAMS). This report provides estimates from 29 states and New York City (NYC) for women who had live births during September 2009-May 2010. Median state coverage was 47.1% for seasonal and 40.4% for pH1N1 influenza vaccination. Overall, women who reported that a health-care provider offered them influenza vaccination or told them to get it during their pregnancy were more likely to be vaccinated than those without an offer or recommendation (prevalence ratio [PR] = 5.2 for seasonal, and PR = 14.4 for pH1N1). Substantial variation across areas was observed for prevalence of a provider offer or recommendation during pregnancy and for influenza vaccination. These findings highlight the need for state-specific strategies that optimize provider involvement to increase influenza vaccination of pregnant women.


title: Selective immobilization of fusion proteins on poly(hydroxyalkanoate) microbeads.

text: A novel fusion protein system employing the substrate-binding domain (SBD) of poly(hydroxyalkanoate) (PHA) depolymerase was developed for the specific immobilization of proteins on PHA microbeads, and was consequently used for immunoassays. The enhanced green fluorescent protein, red fluorescent protein, and severe acute respiratory syndrome coronavirus envelope protein were used as model proteins, and were selectively and functionally immobilized to the PHA microbeads by fusing them to the SBD. Using this PHA microbead system combined with SBD fusion technology, immunoassays could be successfully carried out.


title: The multifunctional nucleolus.

text: The nucleolus is a distinct subnuclear compartment that was first observed more than 200 years ago. Nucleoli assemble around the tandemly repeated ribosomal DNA gene clusters and 28S, 18S and 5.8S ribosomal RNAs (rRNAs) are transcribed as a single precursor, which is processed and assembled with the 5S rRNA into ribosome subunits. Although the nucleolus is primarily associated with ribosome biogenesis, several lines of evidence now show that it has additional functions. Some of these functions, such as regulation of mitosis, cell-cycle progression and proliferation, many forms of stress response and biogenesis of multiple ribonucleoprotein particles, will be discussed, as will the relation of the nucleolus to human diseases.


title: An antiproliferative ribonuclease from fruiting bodies of the wild mushroom Russula delica.

text: An antiproliferative ribonuclease with a new N-terminal sequence was purified from fruiting bodies of the edible wild mushroom Russula delica in this study. This novel ribonuclease was unadsorbed on DEAE-cellulose, but absorbed on SP-Sepharose and Q-Sepharose. It had a molecular mass of 14 kDa as judged by fast protein liquid chromatography on Superdex 75 and SDS-polyacrylamide gel electrophoresis. Its optimal pH and optimal temperature were pH 5 and 60 degrees , respectively. The ranking of its activity toward various polyhomoribonucleotides was poly C > poly G > poly A > poly U. It could inhibit proliferation of HepG2 and MCF-7 cancer cells with an IC50 value of 8.6 microM and 7.2 microM, respectively. It was devoid of antifungal and HIV-1 reverse transcriptase inhibitory activity.


title: Phosphate-binding pocket in Dicer-2 PAZ domain for high-fidelity siRNA production.

text: The enzyme Dicer produces small silencing RNAs such as micro-RNAs (miRNAs) and small interfering RNAs (siRNAs). In Drosophila, Dicer-1 produces ∼22-24-nt miRNAs from pre-miRNAs, whereas Dicer-2 makes 21-nt siRNAs from long double-stranded RNAs (dsRNAs). How Dicer-2 precisely makes 21-nt siRNAs with a remarkably high fidelity is unknown. Here we report that recognition of the 5'-monophosphate of a long dsRNA substrate by a phosphate-binding pocket in the Dicer-2 PAZ (Piwi, Argonaute, and Zwille/Pinhead) domain is crucial for the length fidelity, but not the efficiency, in 21-nt siRNA production. Loss of the length fidelity, meaning increased length heterogeneity of siRNAs, caused by point mutations in the phosphate-binding pocket of the Dicer-2 PAZ domain decreased RNA silencing activity in vivo, showing the importance of the high fidelity to make 21-nt siRNAs. We propose that the 5'-monophosphate of a long dsRNA substrate is anchored by the phosphate-binding pocket in the Dicer-2 PAZ domain and the distance between the pocket and the RNA cleavage active site in the RNaseIII domain corresponds to the 21-nt pitch in the A-form duplex of a long dsRNA substrate, resulting in high-fidelity 21-nt siRNA production. This study sheds light on the molecular mechanism by which Dicer-2 produces 21-nt siRNAs with a remarkably high fidelity for efficient RNA silencing.


title: Single-access retroperitoneal adrenalectomy.

text: AIM To report the first case in our country of a single access--adrenalectomy with lateral retroperitoneal approach by using SILS port and to evaluate the feasibility and safety of this new technique. MATERIALS AND METHODS A 50-year-old man presented with 38 mm right adrenal incidentaloma, functionally nonactive and without radiologic characteristics suggestive of a malignant lesion, discovered on abdominal computed tomography for nephrolithiasis. The single access adrenalectomy was attempted with multichannel SILS port (Covidien), inserted through a 3 cm transverse incision at the tip of rib XII on the right side. RESULTS The single access retroperitoneal adrenalectomy (SARA) was successfully completed without any intraoperative complications. An additional lateral 5-mm port was needed for retraction of the kidney and for tubular drain in the end stage of the surgery. The operating time was 120 minutes with 40 mL of blood loss. Postoperative recovery was uneventful. The patient was discharged from the hospital on the second postoperative day. Pathologic examination confirmed cortical adenoma of the adrenal grand. No morbidity within one month of follow-up, and excellent cosmetic results. CONCLUSION This is the first case of a single access retroperitoneal adrenalectomy (SARA) by using SILS port was performed in our country. Based on our primary experience, we believe that SARA is a safe and feasible procedure for selected patients with adrenal tumors and when performed by a surgeon experienced in laparoscopic and adrenal surgery. Although initial technical adjustments are inevitable, simplifying the procedure. However, more surgical experience using this technique is required to confirm our initial impressions.


title: Primary care physicians in Hong Kong and Canada--how did their practices differ during the SARS epidemic?

text: BACKGROUND Hong Kong and Canada have very different primary health care systems. We thus hypothesized family physicians between the two places would be different in how they protected themselves, their staff and families during the epidemic. OBJECTIVE The purpose of this study was to explore and contrast the impact of SARS on family physicians in Hong Kong and Toronto. METHODS A postal questionnaire was designed and sent to 183 tutors affiliated with the Chinese University of Hong Kong with 137 replies (74.8%). In Toronto, 150 questionnaires were sent to academic family physicians affiliated with the University of Toronto with 51 replies (34%). RESULTS All agreed SARS had changed their clinical behaviour. For public health measures in the control of SARS, Hong Kong physicians were less likely to quarantined themselves (77.1% versus 19.4%, P < 0.01) or gave quarantine leave to staff (95% versus 59.7%, P < 0.01) after exposure to probable or suspected SARS. However, they were more likely to wear a mask (52.7% versus 97.7%, P = 0) during consultation, having support staff to wear masks (68.6% versus 97.8%, P = 0) and test patient's temperature (47.1% versus 68.1%, P < 0.01). CONCLUSION There were noticeable differences in how family physicians deal with SARS between the two cities. As SARS emerged as a global disease, better understanding of practice differences among physicians from different countries would facilitate globalization of public health.


Background paper. Advances in the study of MHV infection of mice.


title: Self-reported asthma among high school students--United States, 2003.

text: Asthma is a leading chronic illness among children in the United States. To examine self-reported asthma and asthma attacks among U.S. high school students, CDC analyzed data from the 2003 national Youth Risk Behavior Survey (YRBS). This report summarizes the results of that analysis, which indicated that 18.9% of high school students had been told by a doctor or nurse that they had asthma, 16.1% had current asthma, and 37.9% of those with current asthma had had an episode of asthma or an asthma attack during the 12 months preceding the survey. These findings underscore the need for health-care providers, schools, families, and public health practitioners to be prepared to respond to asthma-related emergencies and to help students manage their asthma.


title: Emerging infectious diseases: vulnerabilities, contributing factors and approaches.

text: We live in an ever more connected global village linked through international travel, politics, economics, culture and human-human and human-animal interactions. The realization that the concept of globalization includes global exposure to disease-causing agents that were formerly confined to small, remote areas and that infectious disease outbreaks can have political, economic and social roots and effects is becoming more apparent. Novel infectious disease microbes continue to be discovered because they are new or newly recognized, have expanded their geographic range, have been shown to cause a new disease spectrum, have jumped the species barrier from animals to humans, have become resistant to antimicrobial agents, have increased in incidence or have become more virulent. These emerging infectious disease microbes may have the potential for use as agents of bioterrorism. Factors involved in the emergence of infectious diseases are complex and interrelated and involve all classifications of organisms transmitted in a variety of ways. In 2003, outbreaks of interest included severe acute respiratory syndrome, monkeypox and avian influenza. Information from the human genome project applied to microbial organisms and their hosts will provide new opportunities for detection, diagnosis, treatment, prevention, control and prognosis. New technology related not only to genetics but also to satellite and monitoring systems will play a role in weather, climate and the approach to environmental manipulations that influence factors contributing to infectious disease emergence and control. Approaches to combating emerging infectious diseases include many disciplines, such as animal studies, epidemiology, immunology, ecology, environmental studies, microbiology, pharmacology, other sciences, health, medicine, public health, nursing, cultural, political and social studies, all of which must work together. Appropriate financial support of the public health infrastructure including surveillance, prevention, communication, adherence techniques and the like will be needed to support efforts to address emerging infectious disease threats.


title: Treating the host response to emerging virus diseases: lessons learned from sepsis, pneumonia, influenza and Ebola.

text: There is an ongoing threat of epidemic or pandemic diseases that could be caused by influenza, Ebola or other emerging viruses. It will be difficult and costly to develop new drugs that target each of these viruses. Statins and angiotensin receptor blockers (ARBs) have been effective in treating patients with sepsis, pneumonia and influenza, and a statin/ARB combination appeared to dramatically reduce mortality during the recent Ebola outbreak. These drugs target (among other things) the endothelial dysfunction found in all of these diseases. Most scientists work on new drugs that target viruses, and few accept the idea of treating the host response with generic drugs. A great deal of research will be needed to show conclusively that these drugs work, and this will require the support of public agencies and foundations. Investigators in developing countries should take an active role in this research. If the next Public Health Emergency of International Concern is caused by an emerging virus, a "top down" approach to developing specific new drug treatments is unlikely to be effective. However, a "bottom up" approach to treatment that targets the host response to these viruses by using widely available and inexpensive generic drugs could reduce mortality in any country with a basic health care system. In doing so, it would make an immeasurable contribution to global equity and global security.


title: A Hepatozoon species genetically distinct from H. canis infecting spotted hyenas in the Serengeti ecosystem, Tanzania.

text: Health monitoring of spotted hyenas (Crocuta crocuta) in the Serengeti ecosystem, Tanzania, revealed Hepatozoon infection in all of 11 immature individuals examined following death from natural causes. Hepatozoon infection was probably an important factor contributing to mortality in two cases that exhibited clinical signs of ataxia, lethargy, ocular discharge, retching, and labored breathing before death. Whether Hepatozoon infection contributed to six deaths from fire, probable lion predation and unknown causes could not be determined. Four deaths from infanticide and starvation were unlikely to be associated with Hepatozoon infection. Histologic examination revealed lung tissue infected with cyst-like structures containing protozoan stages in all eight cases examined and interstitial pneumonia in most cases. Systemic spread of infection to several organs was found in three cases. Alignment of a 426 bp sequence from the parasite's 18s rRNA gene revealed a Hepatozoon species identical to that recently described from two domestic cats in Spain and only 7 bp substitutions when a 853 bp sequence was aligned to this cat Hepatozoon species. Previous reports of infection of wild carnivores in eastern and southern Africa with an unspecified Hepatozoon species similar in appearance to H. canis may have involved the species described in this study.


title: Effects of Gadodiamide on cell proliferation and collagen production in cultured human dermal fibroblasts.

text: Nephrogenic systemic fibrosis (NSF) is a disease characterized by fibrosis of the systemic organs in patients with renal failure. Following the findings of recent epidemiological studies and the finding of gadolinium (Gd) in the skin tissue of NSF patients, it is now definitely known that the use of Gd contrast agents can trigger NSF. To date, however, the exact mechanism underlying the induction of fibrosis in various organs by Gd remains unexplained. This study was undertaken to evaluate the influence of Gd on the proliferation activity and collagen production of cultured fibroblasts. Normal human dermis-derived fibroblasts were incubated in the presence of gadodiamide (GA) in the concentration range of 5 × 10-7 to 5 × 10-3 M. The proliferation activity of the cells was assessed on the basis of the cell counts in the fibroblast growth curve and the DNA-synthetic activity of the cells (indicator; level of 3H-thymidine uptake by cells). The collagen production was evaluated by densitometric measurement of the quantity of collagen through electrophoresis and fluorography after incorporation of 3H-proline into the procollagens. Furthermore, the expression levels of the genes for type I and III collagen were measured by real-time reverse transcription polymerase chain reaction (RT-PCR) assay. The cell count tended to be higher when the fibroblasts were incubated in medium containing GA in the concentration range of 5 × 10-7 to 5 × 10-4M as compared to that in the GA-free control cultures; furthermore, the DNA-synthetic activity also rose in a concentration-dependent manner in the GA-treated group as compared to that in the control group. No significant changes in either the collagen production or the collagen gene expression levels were noted in cultures containing GA at concentrations between 5 × 10-7 and 5 × 10-3 M. These results suggest that the formation of sclerosing lesions in patients with NSF may be attributable to the effect of GA of enhancing the growth activity of fibroblasts.


title: The SCHOOL of nature: IV. Learning from viruses.

text: During the co-evolution of viruses and their hosts, the latter have equipped themselves with an elaborate immune system to defend themselves from the invading viruses. In order to establish a successful infection, replicate and persist in the host, viruses have evolved numerous strategies to counter and evade host antiviral immune responses as well as exploit them for productive viral replication. These strategies include those that modulate signaling mediated by cell surface receptors. Despite tremendous advancement in recent years, the exact molecular mechanisms underlying these critical points in viral pathogenesis remain unknown. In this work, based on a novel platform of receptor signaling, the Signaling Chain HOmoOLigomerization (SCHOOL) platform, I suggest specific mechanisms used by different viruses such as human immunodeficiency virus (HIV), cytomegalovirus (CMV), severe acute respiratory syndrome coronavirus, human herpesvirus 6 and others, to modulate receptor signaling. I also use the example of HIV and CMV to illustrate how two unrelated enveloped viruses use a similar SCHOOL mechanism to modulate the host immune response mediated by two functionally different receptors: T cell antigen receptor and natural killer cell receptor, NKp30. This suggests that it is very likely that similar general mechanisms can be or are used by other viral and possibly non-viral pathogens. Learning from viruses how to target cell surface receptors not only helps us understand viral strategies to escape from the host immune surveillance, but also provides novel avenues in rational drug design and the development of new therapies for immune disorders.


title: Studies of coronavirus DI RNA replication using in vitro constructed DI cDNA clones.

text: Sequence analysis of an intracellular defective-interfering (DI) RNA, DIssE, of mouse hepatitis virus (MHV) revealed that it is composed of three noncontiguous genomic regions, representing the first 864 nucleotides of the 5'-end, an internal 748 nucleotides of the polymerase gene, and 601 nucleotides from the 3'-end of the parental MHV genome. DIssE had three base substitutions within the leader sequence and also a deletion of nine nucleotides located at the junction of the leader and the remaining genomic sequence. A system was developed for generating DI RNAs to study the mechanism of MHV RNA replication. A cDNA copy of DIssE RNA was placed downstream of T7 RNA polymerase promoter to generate DI RNAs capable of extremely efficient replication in the presence of a helper virus. We demonstrated that, in the DI RNA-transfected cells, the leader sequence of these DI RNAs was switched to that of the helper virus during one round of replication. This high-frequency leader sequence exchange was not observed if a nine-nucleotide stretch at the junction between the leader and the remaining DI sequence was deleted. This observation suggests that a free leader RNA is utilized for the replication of MHV RNA.


title: The murine coronavirus mouse hepatitis virus strain A59 from persistently infected murine cells exhibits an extended host range.

text: In murine 17 Cl 1 cells persistently infected with murine coronavirus mouse hepatitis virus strain A59 (MHV-A59), expression of the virus receptor glycoprotein MHVR was markedly reduced (S. G. Sawicki, J. H. Lu, and K. V. Holmes, J. Virol. 69:5535-5543, 1995). Virus isolated from passage 600 of the persistently infected cells made smaller plaques on 17 Cl 1 cells than did MHV-A59. Unlike the parental MHV-A59, this variant virus also infected the BHK-21 (BHK) line of hamster cells. Virus plaque purified on BHK cells (MHV/BHK) grew more slowly in murine cells than did MHV-A59, and the rate of viral RNA synthesis was lower and the development of the viral nucleocapsid (N) protein was slower than those of MHV-A59. MHV/BHK was 100-fold more resistant to neutralization with the purified soluble recombinant MHV receptor glycoprotein (sMHVR) than was MHV-A59. Pretreatment of 17 Cl 1 cells with anti-MHVR monoclonal antibody CC1 protected the cells from infection with MHV-A59 but only partially protected them from infection with MHV/BHK. Thus, although MHV/BHK could still utilize MHVR as a receptor, its interactions with the receptor were significantly different from those of MHV-A59. To determine whether a hemagglutinin esterase (HE) glycoprotein that could bind the virions to 9-O-acetylated neuraminic acid moieties on the cell surface was expressed by MHV/BHK, an in situ esterase assay was used. No expression of HE activity was detected in 17 Cl 1 cells infected with MHV/BHK, suggesting that this virus, like MHV-A59, bound to cell membranes via its S glycoprotein. MHV/BHK was able to infect cell lines from many mammalian species, including murine (17 Cl 1), hamster (BHK), feline (Fcwf), bovine (MDBK), rat (RIE), monkey (Vero), and human (L132 and HeLa) cell lines. MHV/BHK could not infect dog kidney (MDCK I) or swine testis (ST) cell lines. Thus, in persistently infected murine cell lines that express very low levels of virus receptor MHVR and which also have and may express alternative virus receptors of lesser efficiency, there is a strong selective advantage for virus with altered interactions with receptor (D. S. Chen, M. Asanaka, F. S. Chen, J. E. Shively, and M. M. C. Lai, J. Virol. 71:1688-1691, 1997; D. S. Chen, M. Asanaka, K. Yokomori, F.-I. Wang, S. B. Hwang, H.-P. Li, and M. M. C. Lai, Proc. Natl. Acad. Sci. USA 92:12095-12099, 1995; P. Nedellec, G. S. Dveksler, E. Daniels, C. Turbide, B. Chow, A. A. Basile, K. V. Holmes, and N. Beauchemin, J. Virol. 68:4525-4537, 1994). Possibly, in coronavirus-infected animals, replication of the virus in tissues that express low levels of receptor might also select viruses with altered receptor recognition and extended host range.


title: Altered proteolytic processing of the polymerase polyprotein in RNA(-) temperature sensitive mutants of murine coronavirus.

text: We examined the synthesis and processing of the polymerase polyprotein in RNA(-) temperature sensitive mutant of murine coronavirus strain A59. These temperature sensitive mutants of MHV-A59 synthesize viral RNA at the permissive temperature (33.0 degrees C), but are unable to synthesize viral RNA at the nonpermissive temperature (39.5 degrees C). The ts mutants have been mapped to five different complementation groups in the polymerase gene. The 5'-most complementation groups, Groups A and B, map to a region encoding an autoproteinase responsible for the cleavage of p28, the amino-terminal product of the polymerase polyprotein. We screened six temperature sensitive mutants to determine if there was an alteration in the proteolytic processing of the polymerase polyprotein, particularly in the cleavage of the p28 protein. Two mutants, tsNC9 and tsLA16, had altered proteolytic products at both the permissive and nonpermissive temperatures. One Group B temperature sensitive mutant, designated tsNC11, was defective in the production of p28 protein at the nonpermissive temperature. To further localize the site of the mutation in tsNC11, RNA representing the 5'-most 5.3 kb region of the polymerase gene was transfected into tsNC11-infected cells and virus production monitored. The transfected RNA was able to complement the defect in tsNC11, resulting in viral RNA synthesis and production of viral particles at the nonpermissive temperature. These results indicate that a gene product from the 5.3 kb region of gene 1 is required for coronavirus RNA synthesis.


title: Detection of antibody to avian viruses in human populations.

text: The ability of three avian viruses to elicit antibody response in humans was surveyed for the purpose of identifying zoonotic diseases. Antibody levels in people associated with poultry were compared to those in people having limited poultry association. Antibody levels to three avian viruses: infectious bursal disease virus, a birnavirus; Newcastle disease virus, a paramyxovirus; and avian infectious bronchitis virus, a coronavirus were determined by enzyme-linked immunosorbent assays (ELISA). Differences between the two study groups were evident: people having a known association with poultry showed significantly higher levels of antibodies to Newcastle disease and avian infectious bronchitis virus. Antibodies detected may be due to virus exposure rather than zoonoses.


title: The function of the spike protein of mouse hepatitis virus strain A59 can be studied on virus-like particles: cleavage is not required for infectivity.

text: The spike protein (S) of the murine coronavirus mouse hepatitis virus strain A59 (MHV-A59) induces both virus-to-cell fusion during infection and syncytium formation. Thus far, only syncytium formation could be studied after transient expression of S. We have recently described a system in which viral infectivity is mimicked by using virus-like particles (VLPs) and reporter defective-interfering (DI) RNAs (E. C. W. Bos, W. Luytjes, H. Van der Meulen, H. K. Koerten, and W. J. M. Spaan, Virology 218:52-60, 1996). Production of VLPs of MHV-A59 was shown to be dependent on the expression of M and E. We now show in several ways that the infectivity of VLPs is dependent on S. Infectivity was lost when spikeless VLPs were produced. Infectivity was blocked upon treatment of the VLPs with MHV-A59-neutralizing anti-S monoclonal antibody (MAb) A2.3 but not with nonneutralizing anti-S MAb A1.4. When the target cells were incubated with antireceptor MAb CC1, which blocks MHV-A59 infection, VLPs did not infect the target cells. Thus, S-mediated VLP infectivity resembles MHV-A59 infectivity. The system can be used to identify domains in S that are essential for infectivity. As a first application, we investigated the requirements of cleavage of S for the infectivity of MHV-A59. We inserted three mutant S proteins that were previously shown to be uncleaved (E. C. W. Bos, L. Heijnen, W. Luytjes, and W. J. M. Spaan, Virology 214:453-463, 1995) into the VLPs. Here we show that cleavage of the spike protein of MHV-A59 is not required for infectivity.


title: Identification of Major and Minor Allergens of Black Tiger Prawn (Penaeus monodon) and King Prawn (Penaeus latisulcatus).

text: BACKGROUND Prawns and shrimp are a frequent cause of seafood allergy mediated by IgE antibodies. Penaeus monodon and Penaeus latisulcatus, commonly known as black tiger prawn and king prawn, respectively, are among the most frequently consumed prawns in Malaysia. The aim of this study was to identify the IgE-binding proteins of these 2 prawn species. METHODS Raw and boiled prawn extracts were prepared and then resolved by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). IgE-immunoblotting was then performed using sera from patients with positive skin prick tests to the raw prawn extracts. RESULTS SDS-PAGE analysis of the raw extracts of both prawn species revealed 23 protein bands; the boiled extracts yielded fewer protein bands. The bands in the range of 40 to 100 kDa were sensitive to heat and therefore were not found in the boiled extracts. Immunoblot of raw extracts of black tiger prawns and king prawns yielded 14 and 11 IgE-binding proteins, respectively, with molecular weights of between 15 and 200 kDa. Proteins at 36, 42, and 49 kDa were detected as the major allergens in both species of prawns. A protein of 75 kDa was also identified as a major allergen in black tiger prawns. Other potential allergens were also observed at various molecular masses. CONCLUSION Proteins of 36, 42, and 49 kDa were identified as the major allergens of both species of prawns. The 36 and 42 kDa proteins are hypothesised to be tropomyosin and arginine kinase, respectively. A high molecular weight protein of 75 kDa was found to be an additional major allergen in black tiger prawns.


title: Detection of human bocavirus in Canadian children in a 1-year study.

text: Human bocavirus was detected by PCR in 65 (5.1%) of 1,265 respiratory specimens collected in 2002 and 2003 from the Stollery Children's Hospital from children <17 years of age. The spectrum of illness included upper respiratory infection, croup, bronchiolitis, and pneumonia with a prominence of cough and fever.


title: Proteolytic processing of CXCL11 by CD13/aminopeptidase N impairs CXCR3 and CXCR7 binding and signaling and reduces lymphocyte and endothelial cell migration.

text: CXCR3 ligands were secreted by tissue fibroblasts and peripheral blood-derived mononuclear leukocytes in response to interferon-gamma (IFN-gamma) and Toll-like receptor (TLR) ligands. Subsequent purification and identification revealed the presence of truncated CXCL11 variants missing up to 6 amino acids. In combination with CD26/dipeptidyl peptidase IV, the metalloprotease aminopeptidase N (APN), identical to the myeloid cell marker CD13, rapidly processed CXCL11, but not CXCL8, to generate truncated CXCL11 forms. Truncated CXCL11 had reduced binding, signaling, and chemotactic properties for lymphocytes and CXCR3- or CXCR7-transfected cells. CD13/APN-truncated CXCL11 failed to induce an intracellular calcium increase but was still able to bind and desensitize CXCR3 for intact CXCL11 signaling. CXCL11 efficiently bound to CXCR7, but CXCL11 was not able to induce calcium signaling or ERK1/2 or Akt phosphorylation through CXCR7. CD26-truncated CXCL11 failed to attract lymphocytes but still inhibited microvascular endothelial cell (HMVEC) migration. However, further processing of CXCL11 by CD13 resulted in significant reduction of inhibition of HMVEC migration. Taken together, during inflammation or cancer, CXCL11 processing by CD13 may lead to a reduced number of tumor-infiltrating lymphocytes and in a more angiogenic environment.


Physical interventions to interrupt or reduce the spread of respiratory viruses - resource use implications: a systematic review.


title: The prospective, randomized investigation of the safety and efficacy of telmisartan versus ramipril using ambulatory blood pressure monitoring (PRISMA I).

text: OBJECTIVE To compare the efficacy and safety of once-daily telmisartan and ramipril on blood pressure (BP) reductions during the last 6 h of the dosing interval. PATIENTS AND METHODS In a prospective, randomized, open-label, blinded-endpoint study using ambulatory BP monitoring, 801 patients with mild-to-moderate hypertension were randomly assigned to once-daily treatment with telmisartan 80 mg for 14 weeks or ramipril 5 mg for 8 weeks and then force titrated to ramipril 10 mg for the last 6 weeks. Primary endpoints were the reduction from baseline in the last 6-h mean ambulatory systolic BP (SBP) and diastolic BP (DBP). Secondary endpoints included changes in 24-h, morning, daytime and night-time mean ambulatory BP and ambulatory BP response rates. RESULTS Telmisartan 80 mg produced greater reductions in the last 6-h mean ambulatory SBP and DBP compared with ramipril 5 mg (P < 0.0001) and 10 mg (P < 0.0001), and was superior to ramipril for all secondary ambulatory SBP and DBP endpoints (P < 0.05). Ambulatory BP response rates (24-h mean ambulatory SBP/DBP < 130/80 mmHg or reduction from baseline > or = 10 mmHg) were greater with telmisartan 80 mg (P < 0.01) than with ramipril 5 and 10 mg. Ramipril was associated with a higher incidence of treatment-related cough (5.7 versus 0.5% for telmisartan). CONCLUSIONS Telmisartan was significantly more effective than ramipril in reducing BP throughout the 24-h dosing interval and particularly during the last 6 h, a time when patients appear to be at greatest risk of cerebro- and cardiovascular events. Both drugs were well tolerated, although ramipril was associated with a higher incidence of cough.


title: Paving the road for lung stem cell biology: bronchioalveolar stem cells and other putative distal lung stem cells.

text: New discoveries in stem cell biology are making the biology of solid tissues increasingly complex. Important seminal studies demonstrating the presence of damage-resistant cell populations together with new isolation and characterization techniques suggest that stem cells exist in the adult lung. More detailed in vivo molecular and cellular characterization of bronchioalveolar stem cells (BASCs), other putative lung stem and progenitor cells, and differentiated cells is needed to determine the lineage relationships in adult lung. Lung diseases such as cystic fibrosis or chronic obstructive pulmonary disease, as well as the most common form of lung cancer in the United States, all involve apparent bronchiolar and alveolar cell defects. It is likely that the delicate balance of stem, progenitor, and differentiated cell functions in the lung is critically affected in patients with these devastating diseases. Thus the discovery of BASCs and other putative lung stem cells will lay the foundation for new inroads to understanding lung biology related to lung disease.


title: Expression of hemagglutinin esterase protein from recombinant mouse hepatitis virus enhances neurovirulence.

text: Murine hepatitis virus (MHV) infection provides a model system for the study of hepatitis, acute encephalitis, and chronic demyelinating disease. The spike glycoprotein, S, which mediates receptor binding and membrane fusion, plays a critical role in MHV pathogenesis. However, viral proteins other than S also contribute to pathogenicity. The JHM strain of MHV is highly neurovirulent and expresses a second spike glycoprotein, the hemagglutinin esterase (HE), which is not produced by MHV-A59, a hepatotropic but only mildly neurovirulent strain. To investigate a possible role for HE in MHV-induced neurovirulence, isogenic recombinant MHV-A59 viruses were generated that produced either (i) the wild-type protein, (ii) an enzymatically inactive HE protein, or (iii) no HE at all (A. Lissenberg, M. M. Vrolijk, A. L. W. van Vliet, M. A. Langereis, J. D. F. de Groot-Mijnes, P. J. M. Rottier, and R. J. de Groot, J. Virol. 79:15054-15063, 2005 [accompanying paper]). A second, mirror set of recombinant viruses was constructed in which, in addition, the MHV-A59 S gene had been replaced with that from MHV-JHM. The expression of HE in combination with A59 S did not affect the tropism, pathogenicity, or spread of the virus in vivo. However, in combination with JHM S, the expression of HE, regardless of whether it retained esterase activity or not, resulted in increased viral spread within the central nervous system and in increased neurovirulence. Our findings suggest that the properties of S receptor utilization and/or fusogenicity mainly determine organ and host cell tropism but that HE enhances the efficiency of infection and promotes viral dissemination, at least in some tissues, presumably by serving as a second receptor-binding protein.


title: [Assessment of the psychological status of urologists during the COVID-19 pandemic].

text: The aim of this study was to analyze the symptoms of depression, anxiety, and stress in urologists during the COVID-19 pandemic. MATERIALS AND METHODS 90 urologists aged 25 to 60 years (M=37.27, S.D.=9.53), 93% of them were men, participated in the online survey. They answered questions about their attitude to their job as doctors and the impact of COVID-19. They filled out the Depression, Anxiety and Stress Scales (DASS-21), the Ten Item Personality Inventory (TIPI) and answered questions assessing their sense of control. RESULTS The greatest concern among urologists is the risk of getting infected with COVID-19 (for 30% of the doctors). 43% of urologists state that their profession interesting. A positive attitude to work, as well as the Big Five traits (Conscientiousness, Emotional Stability and Agreeableness) are associated with lower levels of depression, anxiety, stress and lack of control. Working with COVID-19 patients reduces stress and increases the sense of control. Age and high levels of Emotional Stability predicted lower levels of anxiety, depression and stress. DISCUSSION Working with COVID-19 patients allows doctors to feel more control over what is happening. A sense of control, in turn, and a positive attitude towards work are associated with a lower levels of depression, anxiety and stresssymptoms. CONCLUSION The results of this study can be used in selection of therapeutic targets for psychotherapy, administered to doctors; in prevention of symptoms of anxiety, stress and depression among doctors; and in professional selection of doctors for working in crisis situations.


title: Multi-zone modeling of probable SARS virus transmission by airflow between flats in Block E, Amoy Gardens.

text: UNLABELLED More than 300 residents of a private high-rise housing estate were infected with severe acute respiratory syndrome within a short period during the 2003 epidemic in Hong Kong. The outbreak occurred after the identified index patient visited a flat on a middle floor in Block E of the Amoy Gardens estate on two nights. Approximately 45% of the subsequently infected people resided in Block E, while the other 55% of infected cases mainly resided in six other blocks close to Block E. The distribution of the infected flats in Block E conformed to a non-uniform spatial pattern. Probable environmental causes for airborne transmission associated with the air movements between flats in Block E are identified. The well-established multi-zone airflow modeling method was used to analyze the virus-laden bio-aerosol dispersion between flats through door and window leakage areas in Block E under six different scenarios. The distribution of infection risk in Block E matched with the virus concentrations in flats predicted with the use of multi-zone modeling. Our study shows the importance of ventilation design in high-rise residential apartments. PRACTICAL IMPLICATIONS The present study on the Amoy Gardens outbreak presented a scenario in which crowded living spaces might lead to infection disasters. There is a need to improve the current sanitary drainage design and maintenance standards to avoid any leakage of foul gas into the indoor environments. Our study revealed the need for a review of indoor air quality and ventilation design in buildings including offices, homes and hotels. The study has implications to public health in, for example, the control of other airborne respiratory infectious diseases such as influenza, and in bio-terror safety in buildings.


title: Salmonella serotype enteritidis infections among workers producing poultry vaccine--Maine, November-December 2006.

text: On November 15, 2006, the Maine Department of Health and Human Services (MDHHS) was notified of a case of salmonellosis (a nationally notifiable disease) in an employee of a facility that produced poultry vaccine. When a second case of salmonellosis in another employee at the same facility was reported on November 25, MDHHS began an outbreak investigation. Results of that investigation suggested that 21 employees of the facility became ill during a 1-month period from exposure to a strain of Salmonella serotype Enteritidis (SE) that was used in vaccine production. Infection was thought to have resulted from environmental contamination after the spill of a liquid containing a high concentration of SE. As a result, MDHHS recommended that the facility improve its infection-control procedures to better protect workers. This outbreak highlights occupational risks that can be associated with the manufacture of veterinary biologics involving human pathogens.


title: Serum procalcitonin, C-reactive protein and interleukin-6 for distinguishing bacterial and viral pneumonia in children.

text: OBJECTIVE Serum procalcitonin (PCT), C-reactive protein (CRP) and interleukin-6 (IL-6) concentrations were measured in 126 children hospitalized for community-acquired, radiologically confirmed pneumonia to assess whether these host response values could be used to distinguish bacterial from viral pneumonia. METHODS The samples for PCT, CRP and IL-6 measurements were obtained on admission or the first day of hospitalization. The etiology of pneumonia was studied with an extensive panel of methods that detected 6 bacteria and 11 viruses. RESULTS In all, 54% had evidence of bacterial pneumonia, and 32% had evidence of sole viral pneumonia. In 14% of the cases the etiology could not be determined. Children with bacterial pneumonia had significantly higher PCT (median 2.09 ng/ml vs. 0.56 ng/ml, P = 0.019) and CRP concentrations (96 mg/l vs. 54 mg/l, P = 0.008) than those with sole viral etiology. However, the values markedly overlapped. No significant difference in IL-6 concentrations was seen between the two patient groups. Using PCT > or = 2.0 ng/ml, CRP > or = 150 mg/l or IL-6 > or = 40 pg/ml, the specificity was > or =80% for bacterial pneumonia. The sensitivities with these cutoff values were 50% for PCT, 31% for CRP and 34% for IL-6. CONCLUSIONS The results indicate that the measurement of serum PCT, CRP and IL-6 has little value in the differentiation of bacterial and viral pneumonia in children. However, in some patients with very high serum PCT, CRP or IL-6 values, bacterial pneumonia is probable.


title: Acute disseminated encephalomyelitis.

text: Acute disseminated encephalomyelitis (ADEM) is an immune-mediated inflammatory disorder of the CNS characterized by a widespread demyelination that predominantly involves the white matter of the brain and spinal cord. The condition is usually precipitated by a viral infection or vaccination. The presenting features include an acute encephalopathy with multifocal neurologic signs and deficits. Children are preferentially affected. In the absence of specific biologic markers, the diagnosis of ADEM is still based on the clinical and radiologic features. Although ADEM usually has a monophasic course, recurrent or multiphasic forms have been reported, raising diagnostic difficulties in distinguishing these cases from multiple sclerosis (MS). The International Pediatric MS Study Group proposes uniform definitions for ADEM and its variants. We discuss some of the difficulties in the interpretation of available literature due to the different terms and definitions used. In addition, this review summarizes current knowledge of the main aspects of ADEM, including its clinical and radiologic diagnostic features, epidemiology, pathogenesis, and outcome. An overview of ADEM treatment in children is provided. Finally, the controversies surrounding pediatric MS and ADEM are addressed.


title: Curtailing transmission of severe acute respiratory syndrome within a community and its hospital.

text: Severe acute respiratory syndrome (SARS) has been transmitted extensively within hospitals, and healthcare workers (HCWs) have comprised a large proportion of SARS cases worldwide. We present a stochastic model of a SARS outbreak in a community and its hospital. For a range of basic reproductive numbers (R(0)) corresponding to conditions in different cities (but with emphasis on R(0) approximately 3 as reported for Hong Kong and Singapore), we evaluate contact precautions and case management (quarantine and isolation) as containment measures. Hospital-based contact precautions emerge as the most potent measures, with hospital-wide measures being particularly important if screening of HCWs is inadequate. For R(0) = 3, case isolation alone can control a SARS outbreak only if isolation reduces transmission by at least a factor of four and the mean symptom-onset-to-isolation time is less than 3 days. Delays of a few days in contact tracing and case identification severely degrade the utility of quarantine and isolation, particularly in high-transmission settings. Still more detrimental are delays between the onset of an outbreak and the implementation of control measures; for given control scenarios, our model identifies windows of opportunity beyond which the efficacy of containment efforts is reduced greatly. By considering pathways of transmission in our system, we show that if hospital-based transmission is not halted, measures that reduce community-HCW contact are vital to preventing a widespread epidemic. The implications of our results for future emerging pathogens are discussed.


Expression of voltage-gated calcium channels in tumor cell lines of neuroectodermal or other origin.


Infectious bronchitis virus envelope protein targeting: implications for virus assembly.


title: Respiratory viruses in childhood asthma.

text: PURPOSE OF REVIEW Several epidemiological studies have confirmed the association between viral respiratory infections and wheezing episodes or exacerbations of asthma in childhood. In contrast, whether particular viral infections can be protective or able to initiate asthma is still debated; recent studies reported herein have added to our understanding in several different domains, including natural history, virology and mechanisms. RECENT FINDINGS Animal studies support the possibility that severe infections with respiratory syncytial virus early in life may be able to diverge the immune response towards an allergic phenotype; however, in human studies, predisposition seems dominating. Human rhinoviruses are increasingly being shown to be equally important as respiratory syncytial virus even in infancy. Newly discovered respiratory viruses have also been associated with asthma exacerbations. The interferon pathway is currently scrutinized with respect to virus-induced inflammation; furthermore, indications that viral infections may be associated with remodeling phenotypes have been recently published. SUMMARY Notwithstanding the progress in epidemiology and pathogenesis of virus-induced asthma, more effort is needed in assessing possible strategies for treatment. Current treatments seem to be relatively ineffective, but new pathways give a hopeful message for future therapies.


title: What's the plan? The unique challenges facing the home and community care sector in preparing for a pandemic.

text: Recent experience with the outbreak of severe acute respiratory syndrome (SARS) in Canada and the global threat of the H5N1 virus (avian "flu") have increased the appetite for and urgency of pandemic planning as a policy issue. The healthcare setting is one of the most important areas to prepare for such an event, and it is crucial that discussions around doing so include all settings in which care is delivered. As the home and community care sector is increasingly utilized and likely to be relied upon even more during a pandemic, addressing the challenges to occupational health and safety uniquely faced by this sector will be vitally important to the entire health system. A pandemic plan that does not consider healthcare outside of the institutional setting is incomplete and will be likely to fail. This commentary outlines the challenges to providing care in the home and community that must be considered in any plan designed to deal with a pandemic on a system-wide level.


title: Physiological effects of invasive ventilation with neurally adjusted ventilatory assist (NAVA) in a crossover study.

text: BACKGROUND Neurally Adjusted Ventilatory Assist (NAVA) is a mode of assisted mechanical ventilation that delivers inspiratory pressure proportionally to the electrical activity of the diaphragm. To date, no pediatric study has focused on the effects of NAVA on hemodynamic parameters. This physiologic study with a randomized cross-over design compared hemodynamic parameters when NAVA or conventional ventilation (CV) was applied. METHODS After a baseline period, infants received NAVA and CV in a randomized order during two consecutive 30-min periods. During the last 10 min of each period, respiratory and hemodynamic parameters were collected. No changes in PEEP, FiO2, sedation or inotropic doses were allowed during these two periods. The challenge was to keep minute volumes constant, with no changes in blood CO2 levels and in pH that may affect the results. RESULTS Six infants who had undergone cardiac surgery (mean age 7.8 ± 4.1 months) were studied after parental consent. Four of them had low central venous oxygen saturation (ScvO2 < 65 %). The ventilatory settings resulted in similar minute volumes (1.7 ± 0.4 vs. 1.6 ± 0.6 ml/kg, P = 0.67) and in similar tidal volumes respectively with NAVA and with CV. There were no statistically significant differences on blood pH levels between the two modes of ventilation (7.32 ± 0.02 vs. 7.32 ± 0.04, P = 0.34). Ventilation with NAVA delivered lower peak inspiratory pressures than with CV: -32.7 % (95 % CI: -48.2 to -17.1 %, P = 0.04). With regard to hemodynamics, systolic arterial pressures were higher using NAVA: +8.4 % (95 % CI: +3.3 to +13.6 %, P = 0.03). There were no statistically significant differences on cardiac index between the two modes of ventilation. However, all children with a low baseline ScvO2 (<65 %) tended to increase their cardiac index with NAVA compared to CV: 2.03 ± 0.30 vs. 1.91 ± 0.39 L/min.m2 (median ± interquartile, P = 0.07). CONCLUSIONS This pilot study raises the hypothesis that NAVA could have beneficial effects on hemodynamics in children when compared to a conventional ventilatory mode that delivered identical PEEP and similar minute volumes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01490710 . Date of registration: December 7, 2011.


title: Rhinovirus is associated with severe asthma exacerbations and raised nasal interleukin-12.

text: BACKGROUND Rhinovirus (RV) is associated with asthma exacerbations in longitudinal studies, but the role in patients with acute severe asthma who require admission to a hospital emergency room remains to be fully defined. The cytokines interleukin-10 (IL-10) and IL-12 may be elevated or suppressed by viral infections and contribute to a worsening of airway inflammation in asthmatics. OBJECTIVES We assessed the association of RV with acute severe asthma and nasal IL-10 and IL-12. METHODS Patients admitted to a hospital emergency asthma service had nasal aspirates (NAs) taken and peak expiratory flow (PEF) measured on admission and again 7, 28 and 56 days after admission. RV was sought in all NAs using a validated polymerase chain reaction assay and IL-10 and IL-12 were measured on admission and after 56 days in a subgroup of 22 asthmatics and 6 normal controls. RESULTS Thirty-seven asthmatics with a reduced PEF (% predicted) of 50.4 +/- 2.5% (mean +/- SEM) on admission were studied. RV was detected in NAs of 13 patients (35%) on admission, in 6 of the 13 patients after 7 days (16%), in 1 patient after 28 and 56 days and was absent in controls. IL-10 was not increased on admission or after 56 days. Measurements of IL-12 were raised on admission compared to 56 days later in asthmatics with RV detectable (p = 0.04). In asthmatics without RV, nasal IL-12 levels were correlated with PEF measurements over this period (r = 0.5, p < 0.05). CONCLUSIONS A temporal relationship between the presence of nasal RV and emergency room admission for acute severe asthma was found in one third of patients. Low levels of IL-10 during RV infections could contribute to unopposed synthesis of pro-inflammatory cytokines whilst increases in IL-12 may amplify nasal and endobronchial inflammation.


title: High-frequency RNA recombination of murine coronaviruses.

text: The RNA genome of coronaviruses consists of a single species of nonsegmented RNA. In this communication, we demonstrate that the RNA genomes of different strains of murine coronaviruses recombine during mixed infection at a very high frequency. Susceptible cells were coinfected with a temperature-sensitive mutant of one strain of mouse hepatitis virus (MHV) and a wild-type virus of a different strain. Of 21 randomly isolated viruses released from the coinfected cells at the nonpermissive temperature, 2 were recombinants which differed in the site of recombination. After three serial passages of the original virus pool derived from the mixed infection, the majority of the progeny viruses were recombinants. These recombinant viruses represented at least five different recombination sites between the two parental MHV strains. Such a high-frequency recombination between nonsegmented RNA genomes of MHV suggests that segmented RNA intermediates might be generated during MHV replication. We propose that the RNA replication of MHV proceeds in a discontinuous and nonprocessive manner, thus generating free segmented RNA intermediates, which could be used in RNA recombination via a copy-choice mechanism.


title: Consideration of highly active antiretroviral therapy in the prevention and treatment of severe acute respiratory syndrome.

text: We observed that 0 of 19 patients with human immunodeficiency virus type 1 (HIV-1) infection, including those with acquired immunodeficiency syndrome (AIDS), who were hospitalized together and who had close contact with 95 patients with severe acute respiratory syndrome (SARS) on the same hospital floor contracted SARS, whereas 6 of 28 medical workers who served on this floor contracted SARS while caring for these patients. Our investigation found that most of the patients with HIV-1/AIDS were receiving treatment of highly active antiretroviral therapy (HAART) during hospitalization. Coincidentally, a research group from Hong Kong recently reported that patients with SARS who received treatment with the anti-HIV-1 drug lopinavir-ritonavir experienced significantly better clinical outcomes than did those who did not receive lopinavir-ritonavir. On the basis of these observations and studies, we propose that HAART should be considered for patients with SARS and their close contacts when the SARS epidemic reemerges.


Social Media Spread During Covid-19: The Pros and Cons of Likes and Shares.