title: Prior immunization with severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) nucleocapsid protein causes severe pneumonia in mice infected with SARS-CoV.

text: The details of the mechanism by which severe acute respiratory syndrome-associated coronavirus (SARS-CoV) causes severe pneumonia are unclear. We investigated the immune responses and pathologies of SARS-CoV-infected BALB/c mice that were immunized intradermally with recombinant vaccinia virus (VV) that expressed either the SARS-CoV spike (S) protein (LC16m8rVV-S) or simultaneously all the structural proteins, including the nucleocapsid (N), membrane (M), envelope (E), and S proteins (LC16m8rVV-NMES) 7-8 wk before intranasal SARS-CoV infection. The LC16m8rVV-NMES-immunized group exhibited as severe pneumonia as the control groups, although LC16m8rVV-NMES significantly decreased the pulmonary SARS-CoV titer to the same extent as LC16m8rVV-S. To identify the cause of the exacerbated pneumonia, BALB/c mice were immunized with recombinant VV that expressed the individual structural proteins of SARS-CoV (LC16mOrVV-N, -M, -E, -S) with or without LC16mOrVV-S (i.e., LC16mOrVV-N, LC16mOrVV-M, LC16mOrVV-E, or LC16mOrVV-S alone or LC16mOrVV-N + LC16mOrVV-S, LC16mOrVV-M + LC16mOrVV-S, or LC16mOrVV-E + LC16mOrVV-S), and infected with SARS-CoV more than 4 wk later. Both LC16mOrVV-N-immunized mice and LC16mOrVV-N + LC16mOrVV-S-immunized mice exhibited severe pneumonia. Furthermore, LC16mOrVV-N-immunized mice upon infection exhibited significant up-regulation of both Th1 (IFN-gamma, IL-2) and Th2 (IL-4, IL-5) cytokines and down-regulation of anti-inflammatory cytokines (IL-10, TGF-beta), resulting in robust infiltration of neutrophils, eosinophils, and lymphocytes into the lung, as well as thickening of the alveolar epithelium. These results suggest that an excessive host immune response against the nucleocapsid protein of SARS-CoV is involved in severe pneumonia caused by SARS-CoV infection. These findings increase our understanding of the pathogenesis of SARS.


title: Bioterrorism in the United States: a balanced assessment of risk and response.

text: There are many definitions of terrorism and numerous examples of the use of explosives and small arms, especially against civilians and with the objective of instilling fear. Although chemical and biological agents have only rarely been used by terrorists, there has recently been much concern about the threat of bioterrorism and the role of future health personnel in counteracting it. Rational setting of priorities requires the balance of risks against benefits in prevention and preparedness. Adverse effects of preparedness include inappropriate warnings, diversion of resources from other public health measures, both in the United States and overseas and constraints on civil rights. It is argued that the US should counteract the threat of bioterrorism by dealing with its root causes and by strengthening civil rights, international arms control and international law rather than by a self-defeating 'war on terrorism'.


Successful treatment of Tourette's disorder with amisulpride.


title: Severe acute respiratory syndrome coronavirus (SARS-CoV) infection inhibition using spike protein heptad repeat-derived peptides.

text: The coronavirus SARS-CoV is the primary cause of the life-threatening severe acute respiratory syndrome (SARS). With the aim of developing therapeutic agents, we have tested peptides derived from the membrane-proximal (HR2) and membrane-distal (HR1) heptad repeat region of the spike protein as inhibitors of SARS-CoV infection of Vero cells. It appeared that HR2 peptides, but not HR1 peptides, were inhibitory. Their efficacy was, however, significantly lower than that of corresponding HR2 peptides of the murine coronavirus mouse hepatitis virus (MHV) in inhibiting MHV infection. Biochemical and electron microscopical analyses showed that, when mixed, SARS-CoV HR1 and HR2 peptides assemble into a six-helix bundle consisting of HR1 as a central triple-stranded coiled coil in association with three HR2 alpha-helices oriented in an antiparallel manner. The stability of this complex, as measured by its resistance to heat dissociation, appeared to be much lower than that of the corresponding MHV complex, which may explain the different inhibitory potencies of the HR2 peptides. Analogous to other class I viral fusion proteins, the six-helix complex supposedly represents a postfusion conformation that is formed after insertion of the fusion peptide, proposed here for coronaviruses to be located immediately upstream of HR1, into the target membrane. The resulting close apposition of fusion peptide and spike transmembrane domain facilitates membrane fusion. The inhibitory potency of the SARS-CoV HR2-peptides provides an attractive basis for the development of a therapeutic drug for SARS.


title: Mechanism of the maturation process of SARS-CoV 3CL protease.

text: Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by a novel human coronavirus. Viral maturation requires a main protease (3CL(pro)) to cleave the virus-encoded polyproteins. We report here that the 3CL(pro) containing additional N- and/or C-terminal segments of the polyprotein sequences undergoes autoprocessing and yields the mature protease in vitro. The dimeric three-dimensional structure of the C145A mutant protease shows that the active site of one protomer binds with the C-terminal six amino acids of the protomer from another asymmetric unit, mimicking the product-bound form and suggesting a possible mechanism for maturation. The P1 pocket of the active site binds the Gln side chain specifically, and the P2 and P4 sites are clustered together to accommodate large hydrophobic side chains. The tagged C145A mutant protein served as a substrate for the wild-type protease, and the N terminus was first digested (55-fold faster) at the Gln(-1)-Ser1 site followed by the C-terminal cleavage at the Gln306-Gly307 site. Analytical ultracentrifuge of the quaternary structures of the tagged and mature proteases reveals the remarkably tighter dimer formation for the mature enzyme (K(d) = 0.35 nm) than for the mutant (C145A) containing 10 extra N-terminal (K(d) = 17.2 nM) or C-terminal amino acids (K(d) = 5.6 nM). The data indicate that immature 3CL(pro) can form dimer enabling it to undergo autoprocessing to yield the mature enzyme, which further serves as a seed for facilitated maturation. Taken together, this study provides insights into the maturation process of the SARS 3CL(pro) from the polyprotein and design of new structure-based inhibitors.


Health and economic benefits of an accelerated program of research to combat global infectious diseases.


title: Sequence analysis of the gene encoding the fusion glycoprotein of pneumonia virus of mice suggests possible conserved secondary structure elements in paramyxovirus fusion glycoproteins.

text: The gene encoding the fusion (F) glycoprotein of pneumonia virus of mice consists of 1657 bases and contains an open reading frame encoding 537 amino acids which is more similar to the F proteins of pneumoviruses than to those of other paramyxoviruses. Computer-assisted sequence analyses can be combined with data on the antigenicity of various F proteins to suggest a possible arrangement of secondary structure elements common to all pneumovirus and paramyxovirus F proteins.


title: [Ethical guides, criteria for admission in intensive care, palliative care. Multi-society recommendations for allocation of resources during the COVID-19 pandemic].

text: Guidelines on resource allocation, ethics, triage processes with admission and discharge criteria from critical care and palliative care units during the pandemia are here presented. The interdisciplinary and multi-society panel that prepared these guidelines represented by bioethicists and specialists linked to the end of life: clinicians, geriatricians, emergentologists, intensivists, and experts in palliative care and cardiopulmonary resuscitation. The available information indicates that approximately 80% of people with COVID-19 will develop mild symptoms and will not require hospital care, while 15% will require intermediate or general room care, and the remaining 5% will require assistance in intensive care units. The need to think about justice and establish ethical criteria for allocation patients arise in conditions of exceeding available resources, such as outbreaks of diseases and pandemics, with transparency being the main criterion for allocation. These guides recommend general criteria for the allocation of resources relies on bioethical considerations, rooted in Human Rights and based on the value of the dignity of the human person and substantial principles such as solidarity, justice and equity. The guides are recommendations of general scope and their usefulness is to accompany and sustain the technical and scientific decisions made by the different specialists in the care of critically ill patients, but given the dynamic nature of the pandemic, a process of permanent revision and adaptation of recommendations must be ensured.


Severe acute respiratory syndrome coronavirus sequence characteristics and evolutionary rate estimate from maximum likelihood analysis.


Quarantine: voluntary or not?


title: Role of virus receptor-bearing endothelial cells of the blood-brain barrier in preventing the spread of mouse hepatitis virus-A59 into the central nervous system.

text: BALB/c mice develop a neurologic demyelinating disease after inoculation of mouse hepatitis virus (MHV), strain A59, by the intracranial, but not by the intraperitoneal route. To determine the mechanisms that prevent virus spreading through the blood-brain barrier, we analyzed expression of MHVR, a glycoprotein that serves as receptor for mouse hepatitis virus on endothelial cells of cerebral blood vessels. Our results indicated that MHVR was strongly expressed on the endoluminal pole of these cells. In addition, a direct virus binding assay showed that mouse hepatitis virus was able to bind endothelial cells via this receptor. Despite this expression of a functional viral receptor, in normal mice infected with mouse hepatitis virus by the contra-peritoneal route, no in vivo viral replication could be detected in endothelial cells from the brain, contrasting with the equivalent cells from the liver. However, shortly after i.v. administration of sodium dodecylsulfate detergent to the mice, virus infection of some cerebral endothelial cells was detected in a few mice. As a consequence of detergent treatment, virus infection was able to cross the blood-brain barrier. These results suggest that the protective role of the blood-brain barrier against spreading of mouse hepatitis virus A59 into the central nervous system is determined by a specific restriction of viral entry into the endothelial cells of cerebral origin.


title: Development of effective therapies against West Nile virus infection.

text: Since its entry into North America in 1999, West Nile virus has spread throughout the USA and Canada, and now annually causes a clinical spectrum of human disease ranging from a self-limiting acute febrile illness to potentially lethal encephalitis. Although no therapy is currently approved for use in humans, several strategies are being pursued to develop effective prophylaxis and treatments. This review describes the epidemiology, clinical presentation and pathogenesis of West Nile virus infection, and highlights recent progress towards an effective therapy.


title: Transanal Endoscopic Surgery Using Different Single-Port Devices.

text: Currently, there is a new transanal approach to be used for the excision of selected low-risk rectal cancers and broad-based polyps, the transanal endoscopic surgery using a single-port device. We transferred the single port access surgery (SPA) well-established from laparoscopic surgery as an improvement of the transanal endoscopic microsurgery (TEM). The aim of this article is to give an overview about the technical options and our experiences with different devices. Thirteen patients with selected low-risk rectal cancers or broad-based polyps with dysplasia underwent the SPA modified TEM using the SILS Port (Covidien Norwalk, CT), the TriPort (Olympus KeyMed, Southend, UK) or TriPort+ (Olympus KeyMed, Southend, UK), and laparoscopic instruments. The transanal single port procedure was in all cases completely successful without major complications. The transanal placement of SILS Port (Covidien) and TriPort/TriPort+ (Olympus) was easy to perform; a prior dilatation of the anal sphincter was not necessary. With an excellent view, accurate dissection was possible, all of them are appropriate for transanal single-port device. The postoperative follow-up showed an unremarkable examination. The transanal single port surgery with its benefits is a modified way to replace the TEM procedure. Our first experiences showed comfortable feasibility, less postoperative discomfort, and a reduced risk of damage to the anal sphincter.


United Kingdom has its first confirmed case of SARS.


title: Feasibility of radiofrequency ablation as an alternative to surgical intervention in patients with huge multiloculated pyogenic liver abscesses: A retrospective cohort study.

text: This retrospective cohort study investigated the feasibility of radiofrequency (RF) ablation as an alternative to surgical intervention in patients with huge multiloculated pyogenic liver abscesses (PLAs).From August 2010 to April 2016, 83 patients with PLA were admitted to Beijing Chao-Yang Hospital, China. Four of these patients had huge multiloculated PLAs and underwent RF ablation plus antibiotics. The inclusion criteria for RF ablation were as follows: multiloculated PLA confirmed by computed tomography (CT) or magnetic resonance imaging (MRI), widest diameter of the PLA ≥5 cm, failure to respond to or not suitable to treatment with percutaneous drainage (PD), and patient refusal of surgery. The safety and effectiveness of RF ablation were initially assessed. All patients were commenced on antibiotics on admission to our hospital. CT-guided percutaneous catheter drainage was attempted in one patient but was unsuccessful. The main organism isolated from cultures of these patients' blood or abscess samples was Klebsiella pneumoniae (3/4). RF ablation was performed as soon as eligibility according to the above criteria was established.RF ablation was technically successful in all 4 study patients, all PLAs being completely eradicated. The median duration of fever after RF ablation was 4.5 days. No abscesses recurred; thus, this strategy for managing PLA was 100% successful (4/4). No procedure-related deaths or major complications occurred. One patient had an asymptomatic right pleural effusion that resolved with conservative treatment including albumin infusion and diuretics.Our preliminary data indicate that RF ablation is a safe, feasible, and effective treatment for huge multiloculated PLAs. It should be considered as an alternative treatment for patients who fail to respond to or not suitable for PD plus antibiotics and refuse surgical intervention.


title: [To develop a model on severe acute respiratory syndrome epidemics to quantitatively evaluate the effectiveness of intervention measures].

text: OBJECTIVE To build an epidemic model of severe acute respiratory syndrome (SARS) to be used to quantitatively evaluate the effectiveness of intervention measures. METHODS Following the nature of SARS epidemics, an epidemic model of SARS based on SEIR model of infectious disease was built, in which case management group was set up and some parameters related to control measures were included. As an example, data gathered from Beijing was fitted to illustrate its application to quantitatively evaluate the intervention measures. RESULTS In the newly developed model of epidemics, parameters related to control measures could easily be modified. When scenario assumption was used, a model on SARS outbreak under various circumstances of intervention measures could be set. Thus, quantitative evaluation of intervention measures could perfectly be caried out. Pilot study revealed that the fitness existed in modeling the outbreak of SARS in Beijing and the intervention measures implemented around April 20, 2003, had major contribution to the control of SARS. CONCLUSION The model of SARS epidemics seemed to be stable and reliable to be used to evaluate the effectiveness of intervention measures implemented during the SARS outbreak in a quantitative way.


title: Close relationship between SARS-coronavirus and group 2 coronavirus.

text: The sudden appearance and potential lethality of severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) in humans has resulted in a focusing of new attention on the determination of both its origins and evolution. The relationship existing between SARS-CoV and other groups of coronaviruses was determined via analyses of phylogenetic trees and comparative genomic analyses of the coronavirus genes: polymerase (Orf1ab), spike (S), envelope (E), membrane (M) and nucleocapsid (N). Although the coronaviruses are traditionally classed into 3 groups, with SARS-CoV forming a 4th group, the phylogenetic position and origins of SARS-CoV remain a matter of some controversy. Thus, we conducted extensive phylogenetic analyses of the genes common to all coronavirus groups, using the Neighbor-joining, Maximum-likelihood, and Bayesian methods. Our data evidenced largely identical topology for all of the obtained phylogenetic trees, thus supporting the hypothesis that the relationship existing between SARS-CoV and group 2 coronavirus is a monophyletic one. Additional comparative genomic studies, including sequence similarity and protein secondary structure analyses, suggested that SARS-CoV may bear a closer relationship with group 2 than with the other coronavirus groups. Although our data strongly suggest that group 2 coronaviruses are most closely related with SARS-CoV, further and more detailed analyses may provide us with an increased amount of information regarding the origins and evolution of the coronaviruses, most notably SARS-CoV.


Long-term sequelae of SARS: physical, neuropsychiatric, and quality-of-life assessment.


title: Switching species tropism: an effective way to manipulate the feline coronavirus genome.

text: Feline infectious peritonitis virus (FIPV), a coronavirus, is the causative agent of an invariably lethal infection in cats. Like other coronaviruses, FIPV contains an extremely large positive-strand RNA genome of ca. 30 kb. We describe here the development and use of a reverse genetics strategy for FIPV based on targeted RNA recombination that is analogous to what has been described for the mouse hepatitis virus (MHV) (L. Kuo et al., J. Virol. 74:1393-1406, 2000). In this two-step process, we first constructed by targeted recombination a mutant of FIPV, designated mFIPV, in which the ectodomain of the spike glycoprotein was replaced by that of MHV. This switch allowed for the selection of the recombinant virus in murine cells: mFIPV grows to high titers in these cells but has lost the ability to grow in feline cells. In a second, reverse process, mFIPV was used as the recipient, and the reintroduction of the FIPV spike now allowed for selection of candidate recombinants by their regained ability to grow in feline cells. In this fashion, we reconstructed a wild-type recombinant virus (r-wtFIPV) and generated a directed mutant FIPV in which the initiation codon of the nonstructural gene 7b had been disrupted (FIPV Delta 7b). The r-wtFIPV was indistinguishable from its parental virus FIPV 79-1146 not only for its growth characteristics in tissue culture but also in cats, exhibiting a highly lethal phenotype. FIPV Delta 7b had lost the expression of its 7b gene but grew unimpaired in cell culture, confirming that the 7b glycoprotein is not required in vitro. We establish the second targeted RNA recombination system for coronaviruses and provide a powerful tool for the genetic engineering of the FIPV genome.


docid: juxwepbf

title: [Perceived stress in general public during prevalence of severe acute respiratory syndrome and its impact on health behavior].

text: OBJECTIVE To find out the perceived stress in general public during prevalence of severe acute respiratory syndrome (SARS) and its impact on health behavior. METHODS A retrospective survey was conducted in Guangzhou, Hangzhou, and Taiyuan according to the epidemic situations of SARS, and 2532 subjects were randomly selected from constructive industry, school, and commercial business and residents in urban and rural areas. The perceive stress was measured by Chinese perceived stress scale (CPSS), and health related behavior during SARS was tested by uniform and self-made questionnaire. EpiData 2.0 was used for data management and CPSS value was calculated according to answer to 14 questions contained in the scale. Health risk stress among different population group and health related behavior among low, medium and high stress state were analyzed by SPSS 11.5. RESULTS 2424 subjects were involved in the survey. The CPSS value was measured from 0 - 49 (22.7 +/- 6.8), M = 24.0. 39.3% (953/2379) subjects were under the health risk stress. The health related behaviors such as washing hands, opening the window for air, keeping away from others when cough and sneeze, doing exercises etc were reduced with the stress increased. Logistic regression indicated that compared with the persons with the thoughts of nothing serious of SARS, without any dread of SARS, and knowing nothing about prevention of SARS, the perceived stress was significantly related with perceiving of the thread to certain extent (beta = 0.41, Wald chi(2) = 4.84, P = 0.03), worrying little about the epidemic (beta = 0.50, Wald chi(2) = 6.69, P = 0.01), worrying about it to certain extent (beta = 1.39, Wald chi(2) = 48.59, P = 0.00) and scared so much (beta = 1.77, Wald chi(2) = 53.59, P = 0.00), and knowing little about the prevention (beta = 0.74, Wald chi(2) = 4.48, P = 0.03), knowing something about prevention (beta = -0.98, Wald chi(2) = 8.29, P = 0.00) and knowing the prevention very well (beta = -1.18, Wald chi(2) = 10.66, P = 0.00). CONCLUSION The adoption of health related behaviors declined with increase of perceived stress. Opening connection to authority and government, enhancing the awareness of outburst affairs among general public and providing positive social support may be effective ways to reduce the population perceived stress.


title: Robotic Inguinal Hernia Repair: Technique and Early Experience.

text: Laparoscopic inguinal hernia repair has been shown to have multiple advantages compared with open repair such as less postoperative pain and earlier resume of daily activities with a comparable recurrence rate. We speculate robotic inguinal hernia repair may yield equivalent benefits, while providing the surgeon added dexterity. One hundred consecutive robotic inguinal hernia repairs with mesh were performed with a mean age of 56 years (25-96). Fifty-six unilateral hernias and 22 bilateral hernias were repaired amongst 62 males and 16 females. Polypropylene mesh was used for reconstruction. All but, two patients were completed robotically. Mean operative time was 52 minutes per hernia repair (45-67). Five patients were admitted overnight based on their advanced age. Regular diet was resumed immediately. Postoperative pain was minimal and regular activity was achieved after an average of four days. One patient recurred after three months in our earlier experience and he was repaired robotically. Mean follow-up time was 12 months. These data, compared with laparoscopic approach, suggest similar recurrence rates and postoperative pain. We believe comparative studies with laparoscopic approach need to be performed to assess the role robotic surgery has in the treatment of inguinal hernia repair.


title: The quest for a true One Health perspective of brucellosis.

text: One Health is an interdisciplinary collaboration that aims at mitigating risks to human health arising from microorganisms present in non-human animal species, which have the potential to be transmitted and cause disease in humans. Different degrees of scientific collaboration and sectoral integration are needed for different types of zoonotic diseases, depending on the health and associated economic gains that can be expected from a One Health approach. Indeed, mitigating zoonotic risks related to emerging diseases with pandemic potential is different from mitigating risks related to endemic zoonotic diseases like brucellosis. Likewise, management of brucellosis at the wildlife-livestock interface in wildlife conservation areas is in essence different from mitigating transmission of a given Brucella species within its preferential host species, which in turn is different from mitigating the spillover of a given Brucella species to non-preferential host species, humans included. Brucellosis economic models often oversimplify and/or wrongly assess transmission between reservoir hosts and spillover hosts. Moreover,they may not properly value non-market outcomes, such as avoidance of human disease, consumer confidence and conservation biology issues. As a result, uncertainty is such that the economic predictions of these models can be questionable. Therefore, understanding the infection biology of Brucella species is a prerequisite. This paper reviews and highlights important features of the infection biology of Brucella species and the changing epidemiology of brucellosis that need to be integrated into a true One Health perspective of brucellosis.


title: Medical Education Amid the COVID-19 Pandemic.

text: The coronavirus pandemic has shaken the mankind to its core. Social distancing is the most important preventive strategy for the spread of this contagion, short of a vaccine. Implementation of the same has forced many countries in to a complete lock-down. Closure of schools and universities has made education uncertain at all levels. Medical education is no exception. In this pandemic, the need for uninterrupted generation of future doctors is felt more than ever in our living memory. Continuity of medical education is thus imperative. While "Live" patient contact is an irreplaceable tenet of clinical teaching, these extraordinary times demand exceptional measures. Pedagogical innovations involving technology and simulation based teaching (Online lectures, video vase vignettes, virtual simulators, webcasting, online chat-rooms) need to be brought to the forefront. Since the medical educators have been pushed inevitably to rely on technology-based learning, they should not only embrace it but also develop and evaluate its sustainability and application in preclinical and clinical setting. Meanwhile, the students, whose medical educations are stuck in this pandemic time, should realize that there is no bigger teacher than a first-hand experience, and they are eyewitnesses to the making of history.


title: Limitations of forehead infrared body temperature detection for fever screening for severe acute respiratory syndrome.

text: We investigated alternative measurement methodology for infrared body thermometry to increase accuracy for outdoor fever screening during the 2003 SARS epidemic. Our results indicate that the auditory meatus temperature is a superior alternative compared with the forehead body surface temperature due to its close approximation to the tympanic temperature.


title: High frequency of mutations that expand the host range of an RNA virus.

text: The ability of a virus population to colonize a novel host is predicted to depend on the equilibrium frequency of potential colonists (i.e., genotypes capable of infecting the novel host) in the source population. In this study, we investigated the determinants of the equilibrium frequency of potential colonists in the RNA bacteriophage 6. We isolated 40 spontaneous mutants capable of infecting a novel Pseudomonas syringae host and sequenced their host attachment genes to identify the responsible mutations. We observed 16 different mutations in the host attachment gene and used a new statistical approach to estimate that 39 additional mutations were missed by our screen. Phenotypic and fitness assays confirmed that the proximate mechanism underlying host range expansion was an increase in the ability to attach to the novel host and that acquisition of this ability most often imposed a cost for growth rate on two standard hosts. Considered in a population genetic framework, our data suggest that host range mutations should exist in phage populations at an equilibrium frequency (3 x 10(-4)) that exceeds the phage mutation rate by more than two orders of magnitude. Thus, colonization of novel hosts is unlikely to be limited by an inability to produce appropriate mutations.


title: Use of the COOH portion of the nucleocapsid protein in an antigen-capturing enzyme-linked immunosorbent assay for specific and sensitive detection of severe acute respiratory syndrome coronavirus.

text: Antibody detection with a recombinant COOH portion of the severe acute respiratory syndrome (SARS) coronavirus nucleocapsid (N) protein, N13 (amino acids 221 to 422), was demonstrated to be more specific and sensitive than that with the full-length N protein, and an N13-based antigen-capturing enzyme-linked immunosorbent assay providing a convenient and specific test for serodiagnosis and epidemiological study of SARS was developed.


title: Case-Based Surveillance of Pandemic (H1N1) 2009 in Maebashi City, Japan.

text: After national case-based surveillance for pandemic influenza A (H1N1) ceased on July 23, 2009, a daily case-based surveillance system was implemented in Maebashi City, Japan. All medical facilities in the city reported all patients who had positive rapid antigen tests for influenza A. When the epidemic exploded in late October, case-based surveillance for influenza-like illness (ILI) was implemented from November 3, 2009 until the end of the epidemic. A total of 7,781 influenza cases were reported between July 25 and November 2, 2009, with a cumulative incidence rate of 22.5 per 1,000 population. Nearly 70% of the patients were under 15 years old. Between November 3, 2009 and the end of March 2010, a total of 16,394 ILI cases were reported, with a cumulative incidence rate of 47.4 per 1,000 population. Of the ILI cases reported, 63% were in patients younger than 15 years old. Only one death with laboratory confirmation of the H1N1 2009 virus was reported during the epidemic. The age-specific reproduction number among children under 15 years of age was almost 1.40, whereas between children and adults (15 years of age and above) it was considerably less than 1.0. The reproduction number derived from the next-generation matrix using data from September 30 to October 14 was estimated to be 1.48 (95% confidence interval, 1.41-1.56). Among individuals under 15 years of age, the infection rate calculated using the final size equation under the assumption of no mitigation measures was nearly twice the rate reported during the epidemic. These findings indicate that the majority of the transmission of influenza A (H1N1) 2009 in the city occurred among children.


title: Adaptation and serial passage of bovine coronavirus in an established diploid swine testicular cell line and subsequent development of a modified live vaccine.

text: A virulent bovine coronavirus isolate (newborn calf diarrheal) was adapted and serially passaged in an established diploid swine testicular cell line (ST cells). The same cells have been used to produce modified live porcine rotavirus and coronavirus vaccines that are federally licensed and sold worldwide. Growth of the bovine coronavirus resulted in cytopathic effect characterized by cellular stranding and subsequent cell lysis. Virus yields were relatively high in the ST cells and active replication was confirmed by immune electron microscopy and immunofluorescence. Adaptation of bovine coronavirus to a diploid swine cell line has not been previously reported. Different cell culture passage levels of bovine coronavirus were evaluated by oral inoculation of clean-catch, colostrum-deprived calves. A passage level of bovine coronavirus was identified that multiplied in the calf without the clinical signs of disease associated with virulent passages. The modified live bovine coronavirus vaccine remained safe and efficacious even after 5-backpassages in calves. Further efficacy studies have shown that the modified live bovine coronavirus vaccine significantly protected calves from highly virulent challenges with either winter dysentery or newborn calf diarrheal coronavirus isolates.


title: Transoral endoluminal approach to Zenker's diverticulum using Ligasure™. Early clinical experience.

text: The development of minimally invasive procedures has rekindled interest in endoluminal techniques for the management of Zenker's diverticulum. Tissue sealers as employed in laparoscopic surgery have not been previously used for Zenker's diverticulum septotomy.Supported by the established safety of linear cutters, bipolar forceps, and ultrasonic scalpels, we have started a procedure using the Ligasure 5™ tissue sealer. Safety and efficacy results in our early clinical experience are shown for a prospective series of 5 consecutive Zenker's diverticulum cases that were perorally managed with tissue sealing.The procedure was quickly and safely performed in the endoscopy room under sedation. Mean number of seals per patient was 2, and mean procedure duration was 33 minutes. No complications developed during or after the procedure, and patients were discharged with immediate dysphagia relief and adequate oral tolerance. No diverticular relapses occurred after a mean follow-up of 21 months (range 18-30). This procedure may be repeated as often as desired with no need for hospital admission. Safety should be prospectively assessed by further studies using a higher number of procedures.


[Preparing for the next pandemic].


title: Evaluation of a newly designed flow diverter for the treatment of intracranial aneurysms in an elastase-induced aneurysm model, in New Zealand white rabbits.

text: INTRODUCTION In this study, we analyzed angiographic and histologic aneurysm occlusion of a newly designed flow-diverting device. Visibility and flexibility, as well as occlusions of side branches and neointimal proliferation were also evaluated. METHODS Aneurysms were induced in 18 New Zealand white rabbits and treated with a braided, "closed-loop-designed" device of nitinol. Additional devices were implanted in the abdominal aorta to cover the origin of branch arteries. Angiographic follow-ups were performed immediately after placement of the device, after 3 months (n = 9) and 6 months (n = 9). The status of aneurysm occlusion (using a five-point scale) and the patency of branch arteries were assessed. RESULTS Aneurysm occlusion rates were noted as grade 0 in 2 (11 %), grade I in 1 (6 %), grade II in 1 (6 %), grade III in 9 (50 %), and grade IV in 5 (28 %) of 18 aneurysms, respectively, indicating a complete or near-complete occlusion of 78 % under double antiplatelet therapy. Aneurysm occlusion was significantly higher at 6 months follow-up (P = 0.025). Radiopaque markers provided excellent visibility. Limited device flexibility led to incomplete aneurysm neck coverage and grade 0 occlusion rates in two cases. Distal device occlusions were found in three cases, most likely due to an extremely undersized vessel diameter in the subclavian artery. No case of branch artery occlusion was seen. Intimal proliferation and diameter stenosis were moderate. CONCLUSION The tested flow diverter achieved near-complete and complete aneurysm occlusion under double antiplatelet therapy of elastase-induced aneurysms in 78 %, while preserving branch arteries.


title: Antiviral strategies against human coronaviruses.

text: Since the mid 60's the human coronaviruses (HCoV), represented by HCoV-OC43 and HCoV-229E, were generally considered relatively harmless viruses. This status changed dramatically with the emergence of SARS-CoV in 2002/2003. The SARS-CoV pandemic took 774 lives around the globe and infected more than 8000 people in 29 countries. SARS-CoV is believed to be of zoonotic origin, transmitted from its natural reservoir in bats through several animal species (e.g., civet cats, raccoon dogs sold for human consumption in markets in southern China). The epidemic was halted in 2003 by a highly effective global public health response, and SARS-CoV is currently not circulating in humans. The outbreak of SARS-CoV and the danger of its re-introduction into the human population, as well as the danger of the emergence of other zoonotic coronaviral infections triggered an intense survey for an efficient treatment that resulted in the evaluation of several anticoronaviral compounds. HCoV-NL63 and HCoV-HKU1 were identified shortly after the SARS-CoV outbreak. The 4 human coronaviruses HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1 cause mild respiratory illnesses when compared to SARS, but these infections are involved in 10 - 20 % of hospitalizations of young children and immunocompromised adults with respiratory tract illness. Therefore, there is an urgent need for a successful therapy to prevent disease induction or a vaccine to prevent new infections. This review summarizes the current status of anticoronaviral strategies.


15 December News.


title: Acute or chronic immunoneutralization of somatostatin does not affect growth hormone or thyroid hormone secretion in sheep.

text: The effect of acute or chronic immunoneutralization of somatostatin (SRIF) on plasma GH, thyrotrophin (TSH) and thyroid hormones was examined. Acute responses to SRIF immunoneutralization were examined using 30 intact male lambs (19.8 +/- 0.6 kg) assigned to one of five treatment groups such that control (C) lambs received no anti-SRIF immunoglobulin and SRIF-immunized (SI) lambs received 2 mg (SI2), 10 mg (SI10), 20 mg (SI20) or 100 mg (SI100) anti-SRIF immunoglobulin/kg body weight (BW). Control immunoglobulin was administered such that all lambs received 100 mg total immunoglobulin protein/kg BW. Effects of chronic SRIF immunoneutralization were examined using C and SI100 lambs which received additional (40 mg/kg BW) control and anti-SRIF immunoglobulin respectively, 4 and 8 days following the initial dose. Blood samples were collected from all lambs, at 10-min intervals, for 5 h immediately following initial immunoglobulin infusion and, from C and SI100 lambs, at 10-min intervals, for 5 h at 11 days following initial immunoglobulin infusion. At the end of each 5-h sampling period, pituitary and thyroid function was examined by i.v. challenge with thyrotrophin-releasing hormone (TRH; 0.33 microgram/kg BW). Basal plasma GH and thyroxine (T4) and the GH, TSH, T4 and tri-iodothyronine (T3) responses to TRH were not influenced by acute or chronic immunoneutralization of SRIF. Acute, but not chronic, immunoneutralization of SRIF elevated basal plasma T3 in SI100 lambs only. The results suggest that SRIF, under physiological conditions, does not influence GH or thyroid hormone secretion in sheep but may influence thyroid hormone metabolism acutely.


Exchanging health lessons globally.


title: Cutting Edge: TLR2 is required for the innate response to Porphyromonas gingivalis: activation leads to bacterial persistence and TLR2 deficiency attenuates induced alveolar bone resorption.

text: Periodontitis is a chronic inflammatory disease that leads to destruction of the attachment apparatus of the teeth. The presence of particular oral bacteria and the host inflammatory response contribute to disease progression. Porphyromonas gingivalis is a Gram-negative anaerobe considered to be a major periodontal pathogen. Isolated Ags from P. gingivalis activate innate immune cells through TLR2 or TLR4. We challenged TLR2- and TLR4-deficient mice with live P. gingivalis and studied the inflammatory response and bacterial survival. Wild-type and TLR4-deficient mice produced high levels of cytokines in response to P. gingivalis challenge, whereas cytokine levels were nearly absent or delayed in TLR2-deficient mice. Surprisingly, P. gingivalis was cleared far more rapidly in TLR2-deficient mice. In addition, TLR2-deficient mice resisted bone loss following oral infection with P. gingivalis.


docid: hccdktcn

title: RNA sequence analysis of the E2 genes of wildtype and neuroattenuated mutants of MHV-4 reveals a hypervariable domain.


title: [Changes in pulmonary function in SARS patients during the three-year convalescent period].

text: OBJECTIVE To investigate the patterns of pulmonary function in severe acute respiratory syndrome (SARS) patients during three-year convalescent period, and to investigate the changes and the medium and long term effects on pulmonary function of SARS patients. METHODS Pulmonary function tests were conducted for four times in 37 SARS patients during three-year convalescent period. They were discharged from hospital within one month, three months, one year and three years respectively. At the same time, pulmonary function of 15 healthy persons was examined as controls to be used for comparison. RESULTS Compared with the healthy controls, there were significant decrease in forced vital capacity (FVC), vital capacity (VC), one second forced expiratory volume (FEV1), 25%-75% forced expiratory flow (25%-75%FEF) of SARS patients within three years after their discharge from hospital (all P<0.05). There were no significant differences in FEV1/FVC, total lung capacity (TLC), diffusing capacity of the lung for carbon monoxide (DLCO) between the two groups (all P>0.05). Abnormality rate of DLCO in the SARS patients within three years after discharge was significantly decreased (32.4% vs. 5.4%,P<0.05), but no significant differences in FVC, VC, 25%-75%FEF among SARS patients discharged one month and three years from the hospital (all P>0.05). Ten SARS patients showed lower FVC (mild degree in 9 cases, severe degree in 1 case) three years later, 2 patients showed mildly lowered DLCO. CONCLUSION The lung diffusion function of the SARS patients had recovered after they were discharged from hospital within three years, but in 20%-30% patients there is still mild or moderate restrictive ventilation function abnormality and small airway function impairment. The lung functions of most patients have recovered gradually, but in a minority of patients they may be impaired.


Prevention and treatment of swine-origin influenza virus with interferon: an in vivo and ex vivo study.


SARS-associated coronavirus.


title: Endocrine hypertension: An overview on the current etiopathogenesis and management options.

text: Endocrine causes of secondary hypertension include primary aldosteronism, pheochromocytoma, cushing's syndrome, hyperparathyroidism and hypo- and hyperthyroidism. They comprise of the 5%-10% of the causes of secondary hypertension. Primary hyperaldosteronism, the most common of the endocrine cause of hypertension often presents with resistant or difficult to control hypertension associated with either normo-or hypokalemia. Pheochromocytoma, the great mimicker of many conditions, is associated with high morbidity and mortality if left untreated. A complete history including pertinent family history, physical examination along with a high index of suspicion with focused biochemical and radiological evaluation is important to diagnose and effectively treat these conditions. The cost effective targeted genetic screening for current known mutations associated with pheochromocytoma are important for early diagnosis and management in family members. The current review focuses on the most recent evidence regarding causes, clinical features, methods of diagnosis, and management of these conditions. A multidisciplinary approach involving internists, endocrinologists and surgeons is recommended in optimal management of these conditions.


title: Whole Genome Analysis and Targeted Drug Discovery Using Computational Methods and High Throughput Screening Tools for Emerged Novel Coronavirus (2019-nCoV).

text: A novel coronavirus designated as SARS-CoV-2 in February 2020 by World Health organization (WHO) was identified as main cause of SARS like pneumonia cases in Wuhan city in Hubei Province of China at the end of 2019. This been recently declared as Global Pandemic by WHO. There is a global emergency to identify potential drugs to treat the SARS-CoV-2. Currently, there is no specific treatment against the new virus. There is a urgency to identifying potential antiviral agents to combat the disease is urgently needed. An effective and quick approach is to test existing antiviral drugs against. Whole genome analysis and alignment carried out using BLASTn, SMART BLAST and WebDSV 2.0 had shown more than 238 ORF's coding for proteins mostly origin from Bat SARS coronavirus and root genomic origin from Archaea. Molecular docking results against protein targets Furin, papain like proteases, RdRp and Spike glycoprotein had shown paritaprevir, ritonavir, entecavir and chloroquine derivatives are the best drugs to inhibit multi targets of coronavirus infection including natural compounds corosolic acid, baicalin and glycyrrhizic acid with minimal inhibitory concentrations. Thus we propose use of paritaprevir, entecavir, ritonavir and chloroquine derivatives as best drug combination along with niacinamide, folic acid and zinc supplements to treat novel coronavirus infection. We also propose use of plant protease inhibitors (PI's) and Anti-IL8, IL-6, IL-2 as future drug models against coronavirus.


docid: ghadtxnx

title: Middle East respiratory syndrome coronavirus (MERS-CoV) RNA and neutralising antibodies in milk collected according to local customs from dromedary camels, Qatar, April 2014.

text: Antibodies to Middle East respiratory syndrome coronavirus (MERS-CoV) were detected in serum and milk collected according to local customs from 33 camels in Qatar, April 2014. At one location, evidence for active virus shedding in nasal secretions and/or faeces was observed for 7/12 camels; viral RNA was detected in milk of five of these seven camels. The presence of MERS-CoV RNA in milk of camels actively shedding the virus warrants measures to prevent putative food-borne transmission of MERS-CoV.


title: Pathogen subversion of cell-intrinsic innate immunity.

text: The mammalian immune system has evolved under continuous selective pressure from a wide range of microorganisms that colonize and replicate in animal hosts. A complex set of signaling networks initiate both innate and adaptive immunity in response to the diverse pathogens that mammalian hosts encounter. In response, viral and microbial pathogens have developed or acquired sophisticated mechanisms to avoid, counteract and subvert sensors, signaling networks and a range of effector functions that constitute the host immune response. This balance of host response and pathogen countermeasures contributes to chronic infection in highly adapted pathogens that have coevolved with their host. In this review we outline some of the themes that are beginning to emerge in the mechanisms by which pathogens subvert the early innate immune response.


title: Regulation of coronavirus RNA transcription is likely mediated by protein-RNA interactions.

text: Coronavirus mRNA transcription was thought to be regulated by the interaction between the leader RNA and the intergenic (IG) sequence, probably involving direct RNA-RNA interactions between complementary sequences. In this study, we found that a 9-nucleotide sequence immediately downstream of the leader RNA up-regulated mRNA transcription and that a particular strain of mouse hepatitis virus (MHV) lacking this 9-nucleotide transcribed subgenomic mRNA species containing unusually heterogeneous leader-fusion sites. These results suggest that the sequence complementarity between the leader and IG is not necessarily required for mRNA transcription. UV cross-linking experiments using cytoplasmic extracts of uninfected cells and the IG sequence showed that three different cellular proteins bound to IG of the template RNA. Deletion analyses and site-directed mutagenesis of IG further demonstrated a correlation between protein-binding and transcription efficiency, suggesting that these RNA-binding proteins are involved in the regulation of coronavirus mRNA transcription. We propose that coronavirus transcription is regulated by RNA-protein and protein-protein interactions.


title: Seco-pregnane steroids target the subgenomic RNA of alphavirus-like RNA viruses.

text: Plants have evolved multiple mechanisms to selectively suppress pathogens by production of secondary metabolites with antimicrobial activities. Therefore, direct selections for antiviral compounds from plants can be used to identify new agents with potent antiviral activity but not toxic to hosts. Here, we provide evidence that a class of compounds, seco-pregnane steroid glaucogenin C and its monosugar-glycoside cynatratoside A of Strobilanthes cusia and three new pantasugar-glycosides of glaucogenin C of Cynanchum paniculatum, are effective and selective inhibitors to alphavirus-like positive-strand RNA viruses including plant-infecting tobacco mosaic virus (TMV) and animal-infecting Sindbis virus (SINV), eastern equine encephalitis virus, and Getah virus, but not to other RNA or DNA viruses, yet they were not toxic to host cells. In vivo administration of the compounds protected BALB/c mice from lethal SINV infection without adverse effects on the mice. Using TMV and SINV as models, studies on the action mechanism revealed that the compounds predominantly suppress the expression of viral subgenomic RNA(s) without affecting the accumulation of viral genomic RNA. Our work suggested that the viral subgenomic RNA could be a new target for the discovery of antiviral drugs, and that seco-pregnane steroid and its four glycosides found in the two medicinal herbs have the potential for further development as antiviral agents against alphavirus-like positive-strand RNA viruses.


title: Applying a cultural lens to the concept of burnout.

text: Burnout is a unique type of stress syndrome that is pervasively affecting the nursing profession. The literature on burnout is reviewed, and a conceptual framework using Maslach's Burnout Inventory is provided. The culture of organizations is examined with regard to its contribution to the antecedents and consequences of burnout. Leininger's cultural care theory and its relevance to the concept of burnout and culture is discussed. Implications for the amelioration of burnout from the perspective of culture are discussed to stimulate future changes in nursing administration, practice, and education. A culture of trust, support, open communication, and respect can foster healthy work environments and protect against burnout.


title: Cryptosporidium and host resistance: historical perspective and some novel approaches.

text: Cryptosporidium parvum is recognized as a major cause of diarrheal disease in neonatal bovine calves. In addition, this protozoan parasite has emerged as an important cause of disease in both immunocompromised and immunocompetent humans. Despite years of research, no consistently effective means of prevention or treatment are readily available for cryptosporidiosis in any species. Infection through ingestion of contaminated water has been widely documented; C. parvum was reported to be responsible for the largest waterborne outbreak of infectious disease in US history. In addition to its role as a primary disease agent, C. parvum has potential to initiate or exacerbate other gastrointestinal disorders, such as inflammatory bowel disease. Thus, control of C. parvum infection in both animals and humans remains an important objective. Research in our laboratory has focused on understanding mechanisms of resistance to C. parvum. We have demonstrated that acquisition of intestinal flora increases resistance to C. parvum. Substances present in the intestinal mucosa of adult animals can transfer resistance when fed to susceptible infants. Both expression of intestinal enzymes and rate of proliferation of epithelial cells may be altered following C. parvum infection. These and other changes may have profound effects on host resistance to C. parvum.


title: Olfactory neuropathy in severe acute respiratory syndrome: report of A case.

text: This case was a 27 years old female with severe acute respiratory syndrome (SARS). She suffered from typical symptoms of SARS. Although she got almost complete recovery from most symptoms after treatment, she noted acute onset complete anosmia 3 weeks after the onset of her first symptom. Her brain MRI examination did not show definite lesion except an incidental finding of left temporal epidermoid cyst. Her anosmia persisted for more than 2 years during following up. Peripheral neuropathy and myopathy have been reported as a concomitant problem during the convalescent stage of SARS, while the sequel of permanent ansomia in SARS was not reported before. Olfactory neuropathy, which rarely occurred in typical peripheral neuropathy, could be a special type of neuropathy induced by corona virus infection in SARS. Olfactory function test should be taken into routine check-up for patients with SARS. The pathophysiology and therapeutic strategy of this special type of permanent olfactory dysfunction deserve further investigation.


title: [COVID-19 - A RECENT REVIEW].

text: INTRODUCTION Corona disease sprang into our lives towards the end of 2019. In November/December 2019, in Wuhan, Hubei province in China, a SARS-like viral disease with a high adhesive capacity and the potential to endanger the life of the patient was reported. It soon became clear that the disease was very contagious and new hospitals were being built on the site and a General closure was underway. Many doctors from all over China were recruited and sent to the isolated area. Local medical reports were acute respiratory distress syndrome (ARDS)-like, and patients needed respiratory support for oxygenation and some needed ventilation on respiratory devices with significant mortality rates. The disease has since spread to many parts of the world, mainly towards Europe. Hospitals have received hundreds of patients, to the point of partially collapsing the glorious Italian healthcare system. Italy and Spain reported a lung disease that causes severe oxidative disruption but no disruption in ventilation unlike ARDS. Initial post-mortem shows that the main cause of death is thromboembolic. Heart involvement with myocarditis and even heart attacks are beginning to be reported. Various drugs are involved in the treatment plan and are often known to fail. Even promising remedies such as Remdesavir, which is an antiviral drug, are beginning to receive reports from controlled trials, which are not as successful as originally expected. All in all, we continue to wander in the dark, both about the disease and certainly, regarding the treatment. The primary treatment involves maximum efforts for respiratory, hematologic, nephrologic and cardiologic support. In this review, I will try to describe the disease and the enigma concerning suggested treatments.


title: Severe, diffuse fibrinonecrotic pleuropneumonia in a cat affected by multiple viral infection.

text: This communication describes the coinfection with feline panleukopenia virus (FPV), feline herpesvirus 1 (FeHV-1), feline calicivirus (FCV) and feline coronavirus (FCoV) in a 1 year‑old domestic cat living in a feline shelter. The cat was referred to veterinary hospital with clinical signs related to diffuse gastro-intestinal inflammation, it had developed a severe pneumopathy with fibrinous exudation in all body cavities and died 8 days after initial presentation. Pathological findings and biomolecular diagnostic test results were compatible with an initial FPV infection that, in consequence of the lymphoid depletion, has fostered coinfection or reactivation of chronic-latent infections with FeHV-1, FCV, and FCoV. In the reported case, the simultaneous presence of different viruses exacerbated the clinical status of the host, resulting in multiple organ damage and leading it to its death.


title: Application of a snare technique in retrograde chronic total occlusion percutaneous coronary intervention - a step by step practical approach and an observational study.

text: Percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) has recently become popular among interventional cardiologists. CTO originating from the ostium has been one of the most difficult CTO lesions to treat with PCI for a number of reasons. Our aim was to illustrate a specific technique during retrograde CTO PCI referred to as the "snare technique."We retrospectively examined the use of "snare technique" among 371 consecutive retrograde CTO PCIs performed at our institution between 2006 and 2015."Snare technique" was used in 10 patients among the 371 retrograde CTO PCIs. The baseline clinical and angiographic characteristics of patients with or without "snare technique" were similar. The "snare technique" group had significantly fewer side branches at occlusion (30.0% vs 71.2%, P = 0.01) and a higher incidence of externalization (90% vs 25.5%, P < 0.001). The contrast volume was significantly lower in the "snare technique" group (285.0 ± 68.5 vs 379.2 ± 144.0, P = 0.04). The incidence of major complications, retrograde success, or final success did not differ between the groups.The "snare technique" is safe and feasible in retrograde CTO PCI, especially in cases of difficult coronary engagement in cases such as ostial occlusion, challenging coronary anatomy, or retrograde guidewire cannot get in antegrade guiding catheter.


Apocalypse or redemption: responding to extensively drug-resistant tuberculosis.


title: Impact of robotic partial nephrectomy with and without ischemia on renal functions: experience in 34 cases.

text: OBJECTIVE In this study we aimed to compare renal functions in patients who underwent robotic partial nephrectomy (RPN) with on-clamp and zero- ischemia techniques. MATERIAL AND METHODS Between 2009 and 2015, 12 off-clamp and 22 on-clamp RPN procedures were performed on a total of 34 patients in two centers. The main outcome parameters examined were serum creatinine, and estimated glomerular filtration rate (eGFR) during preoperative, immediate postoperative periods, and at postoperative 3rd months. RESULTS There were no statistically significant differences between on-clamp and zero- ischemia groups regarding age, ASA score, BMI, PADUA and R.E.N.A.L. nephrometry scores, operation time and tumor size (p>0.05). Significant differences were found in the duration of hospital stay (3.8±0.9 days vs. 3.0±0.9 days) and amount of blood loss (85.9±49.6 mL vs. 183.3±176.2 mL) between the on-clamp and zero-ischemia groups (p<0.05). Statistically significant differences were found between preoperative and immediate post-operative periods, in terms of eGFR and serum creatinine levels in both groups. Moreover, statistically significant differences were found between preoperative and postoperative 3rd month periods, in the on-clamp group in terms of eGFR and serum creatinine levels. In the zero-ischemia group, the decrease in eGFR and serum creatinine levels at postoperative 3rd month relative to the preoperative period was not statistically significant. CONCLUSION Off-clamp RPN technique is superior, in short-term outcomes involving renal functions, compared to on clamp approach. However, long- term data regarding the renal functions should be evaluated to arrive at a definitive decision.


title: Resolution of primary severe acute respiratory syndrome-associated coronavirus infection requires Stat1.

text: Intranasal inhalation of the severe acute respiratory syndrome coronavirus (SARS CoV) in the immunocompetent mouse strain 129SvEv resulted in infection of conducting airway epithelial cells followed by rapid clearance of virus from the lungs and the development of self-limited bronchiolitis. Animals resistant to the effects of interferons by virtue of a deficiency in Stat1 demonstrated a markedly different course following intranasal inhalation of SARS CoV, one characterized by replication of virus in lungs and progressively worsening pulmonary disease with inflammation of small airways and alveoli and systemic spread of the virus to livers and spleens.


title: Rarity gives a charm: evaluation of trace proteins in plasma and serum.

text: Since plasma potentially contacts every cell as it circulates through the body, it may carry clues both to diagnosis and treatment of disease. It is commonly expected that the growing ability to detect and characterize trace proteins will result in discovery of novel therapeutics and biomarkers; however, the familiar, super-abundant plasma proteins remain a fundamental stumbling block. Furthermore, robust validation of proteomic data is a sometimes overlooked but always necessary component for the eventual development of clinical reagents. This review surveys some of the uses of typical and atypical low-abundance proteins, current analytical methods, existing impediments to discovery, and some innovations that are overcoming the challenges to evaluation of trace proteins in plasma and serum.


title: Experimental inoculation of cats with canine coronavirus and subsequent challenge with feline infectious peritonitis virus.

text: Oronasal inoculation of minimal-disease cats with a virulent field isolate of canine coronavirus elicited a neutralizing antibody response that increased steadily over a two-month period, indicating in vivo amplification of the inoculated dose. A heterologous neutralizing antibody response to transmissible gastroenteritis virus could be detected three weeks after titers to canine coronavirus were first observed and was found to parallel the homologous response at a level approximately one log10 dilution lower. A modest anamnestic response detectable in both assays was observed after a second exposure to canine coronavirus. Cross-reacting antibodies to transmissible gastroenteritis virus were not detected by a kinetics-based enzyme-linked immunosorbent assay (KELA), however, until after cats had received multiple daily doses of canine coronavirus (third exposure). No clinical signs attributable to canine coronavirus were seen in inoculated cats, and virus could not be isolated from fecal or rectal swabs nor identified in fecal specimens by electron microscopy. Both virus-neutralizing and KELA titers were boosted by aerosol challenge with feline infectious peritonitis virus. Antibodies produced in response to canine coronavirus did not sensitize cats to subsequent feline infectious peritonitis virus challenge, but neither did they protect cats against the challenge dose.


title: A PCR-enhanced method for determining the 5' end sequence of mRNAs.

text: A method was developed to amplify ligated cDNA copies of mRNA 5' ends before cloning and sequencing. The method facilitates the study of the 5' end sequence on many molecules of an individual mRNA species. It can also be used to study the 5' end sequence on other kinds of single-stranded RNA molecules.


title: Infectious pathogen detection arrays: viral detection in cell lines and postmortem brain tissue.

text: A unique array-based pathogen chip has been developed for the detection of viral RNA or DNA relevant to pathologies of the central nervous system. A total of 715 unique oligonucleotides (60-mer) representing approximately 100 pathogens were designed based on open reading frames (ORFs) from highly conserved and heterogenic regions within viral families. In addition, viral genes reflecting different stages of pathogen infection were also included to potentially define the stage of the viral infection. Viruses (double-stranded DNA, double- or single-stranded RNA, delta, retroid), parasites, and bacteria were included. Test samples labeled with Cy5 were examined by cohybridization with a reference RNA, labeled with Cy3, to the pathogen microarray chip. Good reproducibility of experiments was observed, based on data generated from duplicate hybridizations and duplicate spots on the microarray platform. A viral transcript detection sensitivity of 1 x 10(3) plaque-forming units (pfus) was achieved using selected cell lines and viruses. These findings suggest that the array-based platform described here is capable of detecting a broad spectrum of viruses in a single assay with relatively high sensitivity, specificity, and reproducibility. This method may be used to provide evidence of viral infection in postmortem tissue from psychiatric patients as well as a wide range of other diagnostic categories.


title: Murine hepatitis virus strain 1 produces a clinically relevant model of severe acute respiratory syndrome in A/J mice.

text: Severe acute respiratory syndrome (SARS) is a life-threatening infectious disease which has been difficult to study and treat because of the lack of a readily available animal model. Intranasal infection of A/J mice with the coronavirus murine hepatitis virus strain 1 (MHV-1) produced pulmonary pathological features of SARS. All MHV-1-infected A/J mice developed progressive interstitial pneumonitis, including dense macrophage infiltrates, giant cells, and hyaline membranes, resulting in death of all animals. In contrast, other mouse strains developed only mild transitory disease. Infected A/J mice had significantly higher cytokine levels, particularly macrophage chemoattractant protein 1 (MCP-1/CCL-2), gamma interferon, and tumor necrosis factor alpha. Furthermore, FGL2/fibroleukin mRNA transcripts and protein and fibrin deposits were markedly increased in the lungs of infected A/J mice. These animals developed a less robust type I interferon response to MHV-1 infection than resistant C57BL/6J mice, and treatment with recombinant beta interferon improved survival. This study describes a potentially useful small animal model of human SARS, defines its pathogenesis, and suggests treatment strategies.


title: How infectious disease outbreaks affect community-based primary care physicians: comparing the SARS and H1N1 epidemics.

text: OBJECTIVE To compare how the infectious disease outbreaks H1N1 and severe acute respiratory syndrome (SARS) affected community-based GPs and FPs. DESIGN A mailed survey sent after the H1N1 outbreak compared with the results of similar survey completed after the SARS outbreak. SETTING Greater Toronto area in Ontario. PARTICIPANTS A total of 183 randomly selected GPs and FPs who provided office-based care. MAIN OUTCOME MEASURES The perceptions of GPs and FPs on how serious infectious disease outbreaks affected their clinical work and personal lives; their preparedness for a serious infectious disease outbreak; and the types of information they want to receive and the sources they wanted to receive information from during a serious infectious disease outbreak. The responses from this survey were compared with the responses of GPs and FPs in the greater Toronto area who completed a similar survey in 2003 after the SARS outbreak. RESULTS After the H1N1 outbreak, GPs and FPs still had substantial concerns about the effects of serious infectious disease outbreaks on the health of their family members. Physicians made changes to various office practices in order to manage and deal with patients with serious infectious diseases. They expressed concerns about the effects of an infectious disease on the provision of health care services. Also, physicians wanted to quickly receive accurate information from the provincial government and their medical associations. CONCLUSION Serious community-based infectious diseases are a personal concern for GPs and FPs, and have considerable effects on their clinical practice. Further work examining the timely flow of relevant information through different health care sectors and government agencies still needs to be undertaken.


Authors' reply.


title: Evaluation of the baculovirus-expressed S glycoprotein of transmissible gastroenteritis virus (TGEV) as antigen in a competition ELISA to differentiate porcine respiratory coronavirus from TGEV antibodies in pigs.

text: The spike (S) glycoprotein of the Miller strain of transmissible gastroenteritis virus (TGEV) was recently cloned and expressed in baculovirus. The recombinant S protein was used as the coating antigen in a competition (blocking) enzyme-linked immunosorbent assay (ELISA) in combination with monoclonal antibodies to the S protein epitope A (conserved on TGEV and porcine respiratory coronavirus [PRCV]) or epitope D (present on TGEV only) to differentiate PRCV- from TGEV-induced antibodies. One set (set A) of 125 serum samples were collected at different times after inoculation of caesarean-derived, colostrum-deprived (n = 52) and conventional young pigs (n = 73) with 1 of the 2 porcine coronaviruses or uninoculated negative controls (TGEV/PRCV/negative = 75/30/20). A second set (set B) of 63 serum samples originated from adult sows inoculated with PRCV and the recombinant TGEV S protein or with mock-protein control and then exposed to virulent TGEV after challenge of their litters. Sera from set A were used to assess the accuracy indicators (sensitivity, specificity, accuracy) of the fixed-cell blocking ELISA, which uses swine testicular cells infected with the M6 strain of TGEV as the antigen source (ELISA 1) and the newly developed ELISA based on the recombinant S protein as antigen (ELISA 2). The sera from set B (adults) were tested for comparison. The plaque reduction virus neutralization test was used as a confirmatory test for the presence of antibodies to TGEV/PRCV in the test sera. The accuracy indicators for both ELISAs suggest that differential diagnosis can be of practical use at least 3 weeks after inoculation by testing the dual (acute/convalescent) samples from each individual in conjunction with another confirmatory (virus neutralization) antibody assay to provide valid and complete differentiation information. Moreover, whereas ELISA 1 had 10-20% false positive results to epitope D for PRCV-infected pigs (set A samples), no false-positive results to epitope D occurred using ELISA 2, indicating its greater specificity. The progression of seroresponses to the TGEV S protein epitopes A or D, as measured by the 2 ELISAs, was similar for both sets (A and B) of samples. Differentiation between TGEV and PRCV antibodies (based on seroresponses to epitope D) was consistently measured after the third week of inoculation.


title: Upper respiratory tract infections in children.

text: Respiratory tract infections are a frequent problem for children, families, and pediatricians. Most such infections are trivial and do not warrant significant concern; however, for some children and some infections, aggressive and effective therapy is important. Much of the literature discussed in this article reflects attempts to clarify and improve appropriate use of antimicrobial therapy for those children in whom it is necessary.


title: [Expert panel recommendations on therapeutic and diagnostic management of urinary incontinence and overactive bladder in women].

text: The expert panel recommendations are issued in order to increase the number of patients with urinary incontinence and overactive bladder receiving appropriate care. The expert panel recommends that urologists, gynecologists and other physicians interested in the field of incontinence should Incontinence question should be actively asked during each physician visit and if the answer is positive it should be followed by detailed questionnaire aiming at disclosing at which occasion patient is loosing urine. The next step should be urogynecological examination and cough stress test. The panel recommends urine dipstick in all women and post void residual urine measurement only in women with voiding difficulties. Other tests, such as ultrasound, cystoscopy urodynamics are not recommended during initial diagnostic procedure. The indications for referral are significant pelvic organ prolapse, haematuria, pain during micturition, recurrent incontinence and infections, suspicion of fistula. The initial management of stress urinary incontinence should include lifestyle interventions, and physiotherapy Use of pessaries is acceptable in women who are not fit or do not want surgical therapy Local estrogen therapy should only be used in women with urogenital atrophy Duloxetin is an option in the pharmacological therapy of stress incontinence, but it doesn't cure the disease. The ineffectiveness of initial procedure should be indication to surgery Alphaadrenomimetic drugs are not recommended in the therapy of urinary incontinence. The initial management of overactive bladder and urgency incontinence should include lifestyle interventions, however fluid restrictions (if fluid load is less than 3000 ml) are not recommended. The cornerstone of overactive bladder and urgency incontinence therapy remains the treatment with anticholinergic drugs. Drugs are only effective when used accordingly to the registered doses. The new generation anticholinergics are recommended over the old ones, especially in frail elderly patients and in patients with concomitant diseases, due to their better safety profile. The evaluation of anticholinergics efficacy should be performed after 2-3 months, then after 6 months.


title: Suppression subtraction hybridization (SSH) and macroarray techniques reveal differential gene expression profiles in brain of sea bream infected with nodavirus.

text: Despite of the impact that viruses have on aquatic organisms, relatively little is known on how fish fight against these infections. In this work, the brain gene expression pattern of sea bream (Sparus aurata) in response to nodavirus infection was investigated. We used the suppression subtractive hybridization (SSH) method to generate a subtracted cDNA library enriched with gene transcripts differentially expressed after 1 day post-infection. Some of the ESTs from the infected tissues fell in gene categories related to stress and immune responses. For the reverse library (ESTs expressed in controls compared with infected tissues) the most abundant transcripts were of ribosomal and mitochondrial nature. Several ESTs potentially induced by virus exposure were selected for in vivo expression studies. We observed a clear difference in expression between infected and control samples for two candidate genes, ubiquitin conjugating enzyme 7 interacting protein, which seems to play an important role in apoptosis and the interferon induced protein with helicase C domain 1 (mda-5) that contributes to apoptosis and regulates the type I IFN production, a key molecule of the antiviral innate response in most organisms.


docid: bkmdlecf

title: Baculovirus expression of turkey coronavirus nucleocapsid protein.

text: The nucleocapsid (N) gene of turkey coronavirus (TCV) was amplified by reverse transcriptase-polymerase chain reaction, cloned, and expressed in the baculovirus expression system. A recombinant baculovirus containing the TCV N gene (rBTCV/N) was identified by polymerase chain reaction and expression of TCV N protein as determined by western immunoblot analysis. Two TCV-specific proteins, 52 and 43 kDa, were expressed by rBTCV/N; one of these proteins, p52, was comparable in size to native TCV N protein. Baculovirus-expressed N proteins were used as antigen in an indirect enzyme-linked immunosorbent assay (ELISA) for detection of TCV-specific antibodies. The ELISA detected antibodies specific for TCV and infectious bronchitis virus, a closely related avian coronavirus, but did not detect antibodies specific for other avian viruses (avian influenza, avian reovirus, avian paramyxovirus 3, avian adenovirus 1, or Newcastle disease virus). These findings indicate that baculovirus-expressed TCV N protein is a suitable source of antigen for ELISA-based detection of TCV-specific antibodies in turkeys.


title: The effect of public health measures on the 1918 influenza pandemic in U.S. cities.

text: During the 1918 influenza pandemic, the U.S., unlike Europe, put considerable effort into public health interventions. There was also more geographic variation in the autumn wave of the pandemic in the U.S. compared with Europe, with some cities seeing only a single large peak in mortality and others seeing double-peaked epidemics. Here we examine whether differences in the public health measures adopted by different cities can explain the variation in epidemic patterns and overall mortality observed. We show that city-specific per-capita excess mortality in 1918 was significantly correlated with 1917 per-capita mortality, indicating some intrinsic variation in overall mortality, perhaps related to sociodemographic factors. In the subset of 23 cities for which we had partial data on the timing of interventions, an even stronger correlation was found between excess mortality and how early in the epidemic interventions were introduced. We then fitted an epidemic model to weekly mortality in 16 cities with nearly complete intervention-timing data and estimated the impact of interventions. The model reproduced the observed epidemic patterns well. In line with theoretical arguments, we found the time-limited interventions used reduced total mortality only moderately (perhaps 10-30%), and that the impact was often very limited because of interventions being introduced too late and lifted too early. San Francisco, St. Louis, Milwaukee, and Kansas City had the most effective interventions, reducing transmission rates by up to 30-50%. Our analysis also suggests that individuals reactively reduced their contact rates in response to high levels of mortality during the pandemic.


title: [Relationship between the severity, course, fatality of severe acute respiratory syndrome patients and the timing of hospitalization].

text: OBJECTIVE To study the relationship of timing of hospitalization and the severity, course, fatality of severe acute respiratory syndrome (SARS) patients. METHOD 1291 hospital records of clinically diagnosed SARS patients with complete data gathered from "2003 Beijing SARS Clinical Database" were analyzed. RESULTS SARS cases were categorized into four groups, according to the time of hospitalization after onset of the disease: within 3 days, during day 4 to day 7, during day 8 to day 14 and after day 14. The numbers of cases for each group were 568, 496, 177 and 50 respectively. Data showed that from group 1 to 4, the prevalence rates of major symptoms on the first day of hospitalization were: (1) 9.7%, 16.5%, 23.1% and 24.0% for "feeling chest pain" (P < 0.001), (2) 7.4%, 13.7%, 19.2% and 22.0% for "suffering from breathing obstruction" (P < 0.001), (3) 32.8%, 44.8%, 59.9% and 48.0%, for "coughing" (P < 0.001) and (4) 14.1%, 22.4%, 27.1% and 18.0% for "coughing up phlegm" (P = 0.0002), respectively. The rates of high respiratory frequency (>or= 24 bits/min.) were 11.1%, 15.5%, 22.8% and 25.5% (P < 0.001). The rates of abnormal chest X-ray were 80.3%, 89.0%, 92.3% and 88.9%, respectively (P = 0.002). The average numbers of abnormal lung field (the lung were divided into 6 fields) were 1.7, 1.9, 2.5 and 2.6 (P < 0.001); The numbers of cases receiving continuous oxygen supply treatment were 33.6%, 50.0%, 53.7% and 74.0% (P < 0.001), and the numbers of cases receiving glucocorticosteroids treatment were 28.2%, 35.9%, 53.7% and 62.0% (P < 0.001), respectively. With cases having had chronic baseline diseases prior to SARS infection, the age-standardized fatality rates were 14.9%, 11.7%, 50.0% and 33.9% (P < 0.001), and the average courses of the disease were 30.3, 34.2, 42.9 and 47.5 days (P < 0.001), respectively. In cases without chronic baseline diseases, the age-standardized fatality rates were 5.3%, 9.8%, 9.2% and 8.3% (P = 0.101), and the average courses for each group were 32.4, 35.3, 40.9 and 47.6 days (P < 0.001), respectively. CONCLUSION Delayed hospitalization would cause the situation of SARS patient to deteriorate, losing the best chance for treatment and increase case fatality. In terms of control program on SARS, emphasize should be paid on decreasing the panic of patients to the disease so as to get early hospitalization.


title: RNA of mouse hepatitis virus.

text: The RNA of mouse hepatitis virus, a coronavirus, was isolated from the virus released early in the infection and analyzed by sucrose gradient sedimentation and electrophoresis. It was found to consist of a piece of single-stranded RNA of about 60S. Its molecular weight was estimated to be 5.4 X 10(6) by electrophoresis in methylmercury-agarose gels. At least one third of the RNA contained polyadenylated sequences. It is, therefore, probably positive stranded. The virus harvested late in the infection contained, in addition to 60S, some 30 to 50S RNA that are possibly degradation products of the 60S RNA. No difference in the electrophoretic behavior could be detected between the RNA isolated from a pathogenic (JHM) and a nonpathogenic (A59) strain.


title: The Impact of SARS on Childbirth Education.

text: The SARS (Severe Acute Respiratory Syndrome) crisis in Toronto in the spring of 2003 had major consequences for prenatal learners. Classes in hospitals were cancelled; many couples were left without any prenatal education. This paper outlines the decision-making process of one programme that was determined to keep classes open. The impact of SARS on hospital procedures is also described. Childbirth educators are encouraged to prepare for future public health emergencies. Strategies to prepare for conducting childbirth education classes during times of crisis are outlined.


title: [Clinical experience from treatment of seven SARS patients].

text: OBJECTIVE To summarize the clinical experience from treatment of patients with severe acute respiratory syndrome (SARS). METHODS Retrospective analysis of seven patients with SARS in Ditan hospital treated since April 22 in 2004 was performed. RESULTS In the 7 patients, 2 were male, 5 were female, and the average age was (35.3 plus/minus 11.3) years. The main clinical manifestations were fever, cough, minor or serious dyspnea, nausea, signs of injury to other organs, and so on. The treatment regiments included oxygen, small dosage and short period of methylprednisolone (1 to 2 mg/kg), use of ventilator, psychological intervention, and treatment of underlying diseases, after which, all the 7 patients recovered. CONCLUSION Rational use of methylprednisolone and timely use of ventilator were the key steps of treatment.


title: Use of viral lysate antigen combined with recombinant protein in Western immunoblot assay as confirmatory test for serodiagnosis of severe acute respiratory syndrome.

text: A Western immunoblot assay for confirmatory serodiagnosis of severe acute respiratory syndrome (SARS) was developed utilizing viral lysate antigens combined with a recombinant nucleocapsid protein, GST-N (glutathione S-transferase-nucleocapsid) of the SARS coronavirus (SARS-CoV). The viral lysate antigens were separated by electrophoresis and transblotted onto nitrocellulose membranes. The resultant membrane was subsequently added with the GST-N recombinant protein at a specific location. The positions of bands corresponding to some of the structural proteins immobilized on the membrane were then located and verified with mouse or rabbit antisera specific to the respective proteins. The Western immunoblot assay was able to detect antibodies to SARS-CoV in all 40 serum specimens from SARS patients and differentiate the SARS-positive samples from those of the healthy donor or non-SARS patient controls (150 samples) when set criteria were followed. In addition, when the immunoblot was used to test samples considered falsely positive by an in-house-developed SARS-specific enzyme-linked immunosorbent assay, band patterns different from those with samples from SARS patients were obtained.


title: The small envelope protein E is not essential for murine coronavirus replication.

text: The importance of the small envelope (E) protein in the assembly of coronaviruses has been demonstrated in several studies. While its precise function is not clearly defined, E is a pivotal player in the morphogenesis of the virion envelope. Expression of the E protein alone results in its incorporation into vesicles that are released from cells, and the coexpression of the E protein with the membrane protein M leads to the assembly of coronavirus-like particles. We have previously generated E gene mutants of mouse hepatitis virus (MHV) that had marked defects in viral growth and produced virions that were aberrantly assembled in comparison to wild-type virions. We have now been able to obtain a viable MHV mutant in which the entire E gene, as well as the nonessential upstream genes 4 and 5a, has been deleted. This mutant (Delta E) was obtained by a targeted RNA recombination method that makes use of a powerful host range-based selection system. The Delta E mutant produces tiny plaques with an unusual morphology compared to plaques formed by wild-type MHV. Despite its low growth rate and low infectious titer, the Delta E mutant is genetically stable, showing no detectable phenotypic changes after several passages. The properties of this mutant provide further support for the importance of E protein in MHV replication, but surprisingly, they also show that E protein is not essential.


title: The RNA structures engaged in replication and transcription of the A59 strain of mouse hepatitis virus.

text: In addition to the RI (replicative intermediate RNA) and native RF (replicative form RNA), mouse hepatitis virus-infected cells contained six species of RNA intermediates active in transcribing subgenomic mRNA. We have named these transcriptive intermediates (TIs) and native transcriptive forms (TFs) because they are not replicating genome-sized RNA. Based on solubility in high salt solutions, approximately 70% of the replicating and transcribing structures that accumulated in infected cells by 5-6 h post-infection were multi-stranded intermediates, the RI/TIs. The other 30% were in double-stranded structures, the native RF/TFs. These replicating and transcribing structures were separated by velocity sedimentation on sucrose gradients or by gel filtration chromatography on Sepharose 2B and Sephacryl S-1000, and migrated on agarose gels during electrophoresis, according to their size. Digestion with RNase T1 at 1-10 units/microgram RNA resolved RI/TIs into RF/TF cores and left native RF/TFs intact, whereas RNase A at concentrations of 0.02 microgram/microgram RNA or higher degraded both native RF/TFs and RI/TIs. Viral RI/TIs and native RF/TFs bound to magnetic beads containing oligo(dT)(25), suggesting that the poly(A) sequence on the 3' end of the positive strands was longer than any poly(U) on the negative strands. Kinetics of incorporation of [(3)H]uridine showed that both the RI and TIs were transcriptionally active and the labelling of RI/TIs was not the dead-end product of aberrant negative-strand synthesis. Failure originally to find TIs and TF cores was probably due to overdigestion with RNase A.


title: [Optimization of expression condition of SARS-CoV PUPs genes in E. coli].

text: According to previous studies of SARS-CoV (Severe acute respiratory syndrome coronavirus), a variety of novel accessory genes have been identified in SARS-CoV genome, which were interspersed the structural genes of SARS-CoV and considered to be unique to the SARS-CoV genome. The predicted unknown proteins (PUPs) encoded by the accessory genes might play important roles in the SARS-CoV infection. Three of those genes, called X4, X5 and ORF10, were synthesized and introduced into E. coli to induce expression. SDS-PAGE and Western blotting revealed that the three genes have been expressed in E. coli. The induction of SARS PUPs genes expression in different temperatures, induction times, IPTG concentrations and A values of E. coli cells were performed. The optimal induction condition of SARS-CoV PUPs genes was characterized according to the orthorgonal analysis. The ratio of recombinant proteins of PUPs to total proteins is as follows: X4, 20%; X5, 27.8%; ORF10, 68.5% under the optimum conditions.


title: 'Getting the biosecurity architecture right' in the Asia-Pacific region.

text: This paper offers insights to enhance biosecurity in the Asia-Pacific by asking three questions. What risks/threats are significant in the region? Which security measures should be prioritized? What kind of regional--institutionalized and ad-hoc--arrangements should be implemented? By doing so the paper specifically focuses on two important aspects of biosecurity. Firstly, the issue of immediate capacity-building in the context of disaster relief, public health preparedness and biodefence. Secondly, the long-term preventive aspect, namely education and awareness-raising activities to more broadly promote responsible conduct in life science research in terms of laboratory accidents as well as the intentional use of biological agents for hostile purposes. In order to promote both aspects of biosecurity within the policy process, the paper analyses the strategic value of the US-Japan partnership in its efforts to build a biosecurity architecture in the Asia-Pacific region.


title: An investigation into respiratory tract viruses in children with acute lower respiratory tract infection or wheezing.

text: BACKGROUND This study aimed to determine the frequencies of respiratory tract viruses in patient (acute lower respiratory tract infection (LRTI) or wheezing) and control (history of asthma without symptoms) groups. METHODS Using multiplex-PCR, respiratory tract viruses were investigated in the respiratory tract specimens from patient and control groups followed in the Pediatric Clinic. RESULTS The viruses detected in the patient and control groups (p=0.013) were as follows, respectively: rhinoviruses A, B, C (25.6% and 36.7%), influenza virus A (21.1% and 0.0%), parainfluenza virus type 1 (7.8% and 1.7%), parainfluenza virus type 4 (5.6% and 0.0%), adenoviruses A, B, C, D, E (4.4% and 1.7%), parainfluenza virus type 3 (4.4% and 1.7%), coronaviruses 229E and NL63 (4.4% and 1.7%), coronavirus OC43 (3.3% and 0.0%), respiratory syncytial virus A (3.3% and 0.0%), parainfluenza virus type 2 (2.2% and 0.0%), influenza virus B (2.2% and 0.0%), and respiratory syncytial virus B (1.1% and 1.7%). No bocavirus, metapneumovirus or enterovirus was found in any specimen. Statistically significant differences in the detection of influenza virus A (p=0.000), the total detection of parainfluenza viruses (p=0.008) and co-infection (p=0.004) were observed between the patient and control groups. CONCLUSIONS The advantage of our study compared with other studies is the inclusion of not only wheezing patients but also children with asthma without symptom. The higher detection of Rhinoviruses both in patient and control groups give rise to thought that these viruses may be responsible for asthma exacerbations and may be related with long duration of virus shedding.


title: Nitric oxide up-regulates the glucocorticoid receptor and blunts the inflammatory reaction in porcine endotoxin sepsis.

text: OBJECTIVES Nitric oxide inhibits the expression of many genes involved in inflammatory diseases. Glucocorticoids inhibit similar transcription factors. We hypothesized that there may be an interaction between nitric oxide and glucocorticoids, with the potential to enhance the anti-inflammatory effect when administered simultaneously. DESIGN Prospective, randomized, controlled study. SETTING Animal research laboratory. SUBJECTS A total of 45 anesthetized and mechanically ventilated pigs. INTERVENTIONS Lung and systemic injury was induced by intravenous infusion of endotoxin (lipopolysaccharide) for 6 hrs. After 2.5 hrs, one group received 3.5 mg/kg hydrocortisone, another group inhaled nitric oxide (30 ppm), and still another group received both steroid and nitric oxide. Control groups of healthy and endotoxin-exposed piglets were also studied. MEASUREMENTS AND MAIN RESULTS Central hemodynamics and gas exchange were measured. Detection of the glucocorticoid receptor and inflammatory markers in lung, liver, and kidney tissue were made by immunohistochemistry, and morphology was studied with light microscopy. Endotoxin infusion markedly reduced glucocorticoid receptor expression in lung, liver, and kidney and up-regulated activator protein-1 and the inflammatory markers nuclear factor-kappaB and tumor necrosis factor-alpha. When administered separately, steroids and nitric oxide had modest effect on the inflammatory response. However, nitric oxide up-regulated the glucocorticoid receptor expression. Simultaneous administration of steroids and nitric oxide attenuated the inflammatory response and almost preserved or restored normal histology of both lung and systemic organs. When the glucocorticoid receptor was blocked by a receptor antagonist (mifepristone, 600 mg) and inhaled nitric oxide was subsequently administered, no increase in the expression of the glucocorticoid receptor was seen. CONCLUSION We suggest that up-regulation of glucocorticoid receptor expression by nitric oxide made steroid therapy more effective.


title: Evaluation of the effectiveness of two infectious bronchitis virus vaccine programs for preventing disease caused by a California IBV field isolate.

text: Infectious bronchitis virus CA99 serotype was isolated from several broiler flocks in Northern California. The virus caused late-onset respiratory disease and increased airsacculitis condemnation in affected flocks despite the use of an established infectious bronchitis virus vaccination program. An experimental study compared Holland/Arkansas and Massachusetts/Arkansas vaccination protocols to determine the efficacy of commercial infectious bronchitis virus vaccines in reducing respiratory disease and airsacculitis lesions found at processing that were associated with a CA99 field isolate. All vaccination groups were given Massachusetts/Connecticut strains of infectious bronchitis virus vaccines at age 1 day followed by vaccination with either Holland/ Arkansas or Massachusetts/Arkansas vaccine strains at 18 days of age. Birds were challenged at age 31 days with a CA99 field isolate. Gross pathology, histopathology, and virus isolation were evaluated. Chickens vaccinated with Holland/Arkansas had marginally better protection against CA99 challenge than chickens vaccinated with Massachusetts/Arkansas, although differences were not statistically significant.


title: Interleukin-11: stimulation in vivo and in vitro by respiratory viruses and induction of airways hyperresponsiveness.

text: To address the role of IL-11 in viral airways dysfunction, we determined whether infectious agents that exacerbate asthma stimulate stromal cell IL-11 production, determined whether IL-11 could be detected at sites of viral infection and evaluated the effects of IL-11 on airway physiology. Respiratory syncytial virus (RSV), parainfluenza virus type 3 (PIV3), and rhinovirus (RV) 14 were potent stimulators while cytomegalovirus and adenovirus only weakly stimulated and herpes simplex virus type 2 and bacteria did not stimulate IL-11 elaboration. IL-11 was not detected or barely detected in nasal aspirates from children without, but was detected in aspirates from children with viral upper respiratory tract infections. The levels of IL-11 were highest in patients with clinically detectable wheezing. IL-11 also caused nonspecific airways hyperresponsiveness in BALB/c mice. These studies demonstrate that three major causes of viral-induced asthma, RSV, RV, and PIV, in contrast to other viruses and bacteria, share the ability to induce stromal cell IL-11 production. They also demonstrate that IL-11 can be detected in vivo during viral respiratory infections, that the presence of IL-11 correlates with clinical bronchospasm and that IL-11 is a potent inducer of airways hyperresponsiveness. IL-11 may be an important mediator in viral airways disorders.


ICES report: five policy recommendations from Toronto's SARS outbreak to improve the safety and efficacy of restrictions on hospital admissions to manage infectious disease outbreaks.


docid: djpwtaow

title: Droplet fate in indoor environments, or can we prevent the spread of infection?

text: UNLABELLED When considering how people are infected and what can be done to prevent the infections, answers from many disciplines are sought: microbiology, epidemiology, medicine, engineering, and physics. There are many pathways to infection spread, and among the most significant from the epidemiological point of view is airborne transport. Microorganisms can become airborne when droplets are generated during speech, coughing, sneezing, vomiting, or atomization of feces during sewage removal. The fate of the droplets is governed by the physical principles of transport, with droplet size being the most important factor affecting their dispersion, deposition on surfaces and determining the survival of microorganisms within the droplets. In addition, physical characteristics of the indoor environment as well as the design and operation of building ventilation systems are of critical importance. Do we understand the mechanisms of infection spread and can we quantify the droplet dynamics under various indoor conditions? Unfortunately no, as this aspect of infection spread has attracted surprisingly little scientific interest. However, investigations of numerous cases in which a large number of people were infected show how critical the physics of microorganism spread can be. This paper reviews the state of knowledge regarding mechanisms of droplet spread and solutions available to minimize the spread and prevent infections. PRACTICAL IMPLICATIONS Every day tens of millions of people worldwide suffer from viral infections of different severity at immense economic cost. There is, however, only minimal understanding of the dynamics of virus-laden aerosols, and so the ability to control and prevent virus spread is severely reduced, as was clearly demonstrated during the recent severe acute respiratory syndrome epidemic. This paper proposes the direction to significantly advance fundamental and applied knowledge of the pathways of viral infection spread in indoor atmospheric systems, through a comprehensive multidisciplinary approach and application of state-of-the-art scientific methods. Knowledge gained will have the potential to bring unprecedented economical gains worldwide by minimizing/reducing the spread of disease.