Emergence of enteric viruses in production chickens is a concern for avian health

Several viruses have been identified in recent years in the intestinal contents of chickens and turkeys with enteric problems, which have been observed in commercial farms worldwide, including Brazil. Molecular detection of these viruses in Brazil can transform to a big threat for poultry production due to risk for intestinal integrity. This disease is characterized by severely delayed growth, low uniformity, lethargy, watery diarrhea, delayed feed consumption, and a decreased conversion rate. Chicken astrovirus (CAstV), rotavirus, reovirus, chicken parvovirus (ChPV), fowl adenovirus of subgroup I (FAdV-1), and avian nephritis virus (ANV) were investigated using the conventional polymerase chain reaction (PCR) and the reverse transcription polymerase chain reaction (RT-PCR). In addition, the infectious bronchitis virus (IBV), which may play a role in enteric disease, was included. The viruses most frequently detected, either alone or in concomitance with other viruses, were IBV, ANV, rotavirus, and CAstV followed by parvovirus, reovirus, and adenovirus. This study demonstrates the diversity of viruses in Brazilian chicken flocks presenting enteric problems characterized by diarrhea, growth retard, loss weight, and mortality, which reflects the multicausal etiology of this disease

Über das Vermessen tubulärer Strukturen in der Computertomographie

Die chronisch obstruktive Lungenerkrankung (engl. chronic obstructive pulmonary disease, COPD) ist ein Überbegriff für Erkrankungen, die zu Husten, Auswurf und Dyspnoe (Atemnot) in Ruhe oder Belastung führen - zu diesen werden die chronische Bronchitis und das Lungenemphysem gezählt. Das Fortschreiten der COPD ist eng verknüpft mit der Zunahme des Volumens der Wände kleiner Luftwege (Bronchien). Die hochauflösende Computertomographie (CT) gilt bei der Untersuchung der Morphologie der Lunge als Goldstandard (beste und zuverlässigste Methode in der Diagnostik). Möchte man Bronchien, eine in Annäherung tubuläre Struktur, in CT-Bildern vermessen, so stellt die geringe Größe der Bronchien im Vergleich zum Auflösungsvermögen eines klinischen Computertomographen ein großes Problem dar. In dieser Arbeit wird gezeigt wie aus konventionellen Röntgenaufnahmen CT-Bilder berechnet werden, wo die mathematischen und physikalischen Fehlerquellen im Bildentstehungsprozess liegen und wie man ein CT-System mittels Interpretation als lineares verschiebungsinvariantes System (engl. linear shift invariant systems, LSI System) mathematisch greifbar macht. Basierend auf der linearen Systemtheorie werden Möglichkeiten zur Beschreibung des Auflösungsvermögens bildgebender Verfahren hergeleitet. Es wird gezeigt wie man den Tracheobronchialbaum aus einem CT-Datensatz stabil segmentiert und mittels eines topologieerhaltenden 3-dimensionalen Skelettierungsalgorithmus in eine Skelettdarstellung und anschließend in einen kreisfreien Graphen überführt. Basierend auf der linearen System Theorie wird eine neue, vielversprechende, integral-basierte Methodik (IBM) zum Vermessen kleiner Strukturen in CT-Bildern vorgestellt. Zum Validieren der IBM-Resultate wurden verschiedene Messungen an einem Phantom, bestehend aus 10 unterschiedlichen Silikon Schläuchen, durchgeführt. Mit Hilfe der Skelett- und Graphendarstellung ist ein Vermessen des kompletten segmentierten Tracheobronchialbaums im 3-dimensionalen Raum möglich. Für 8 zweifach gescannte Schweine konnte eine gute Reproduzierbarkeit der IBM-Resultate nachgewiesen werden. In einer weiteren, mit IBM durchgeführten Studie konnte gezeigt werden, dass die durchschnittliche prozentuale Bronchialwandstärke in CT-Datensätzen von 16 Rauchern signifikant höher ist, als in Datensätzen von 15 Nichtrauchern. IBM läßt sich möglicherweise auch für Wanddickenbestimmungen bei Problemstellungen aus anderen Arbeitsgebieten benutzen - kann zumindest als Ideengeber dienen. Ein Artikel mit der Beschreibung der entwickelten Methodik und der damit erzielten Studienergebnisse wurde zur Publikation im Journal IEEE Transactions on Medical Imaging angenommen.

Immunofluorescence versus xTAG multiplex PCR for the detection of respiratory picornavirus infections in children

BACKGROUND: Polymerase chain reaction (PCR) is a sensitive tool for detection of respiratory picornaviruses. However, the clinical relevance of picornavirus detection by PCR is unclear. Immunofluorescence (IF), widely used to detect other respiratory viruses, has recently been introduced as a promising detection method for respiratory picornaviruses. OBJECTIVES: To compare the clinical manifestations of respiratory picornavirus infections detected by IF with those of respiratory picornavirus infections detected by xTAG multiplex PCR in hospitalized children. STUDY DESIGN: During a 1-year period, nasopharyngeal aspirates (NPA) from all children hospitalized due to an acute respiratory infection were prospectively analyzed by IF. All respiratory picornavirus positive IF samples and 100 IF negative samples were further tested with xTAG multiplex PCR. After exclusion of children with co-morbidities and viral co-infections, monoinfections with respiratory picornaviruses were detected in 108 NPA of 108 otherwise healthy children by IF and/or PCR. We compared group 1 children (IF and PCR positive, n=84) with group 2 children (IF negative and PCR positive, n=24) with regard to clinical manifestations of the infection. RESULTS: Wheezy bronchitis was diagnosed more often in group 1 than in group 2 (71% vs. 46%, p=0.028). In contrast, group 2 patients were diagnosed more frequently with pneumonia (17% vs. 6%, p=0.014) accompanied by higher levels of C-reactive protein (46mg/l vs. 11mg/l, p=0.009). CONCLUSIONS: Picornavirus detection by IF in children with acute respiratory infection is associated with the clinical presentation of wheezy bronchitis. The finding of a more frequent diagnosis of pneumonia in picornavirus PCR positive but IF negative children warrants further investigation.

Embryonic exposure to corticosterone modifies the juvenile stress response, oxidative stress, and telomere length.

Early embryonic exposure to maternal glucocorticoids can broadly impact physiology and behaviour across phylogenetically diverse taxa. The transfer of maternal glucocorticoids to offspring may be an inevitable cost associated with poor environmental conditions, or serve as a maternal effect that alters offspring phenotype in preparation for a stressful environment. Regardless, maternal glucocorticoids are likely to have both costs and benefits that are paid and collected over different developmental time periods. We manipulated yolk corticosterone (cort) in domestic chickens (Gallus domesticus) to examine the potential impacts of embryonic exposure to maternal stress on the juvenile stress response and cellular ageing. Here, we report that juveniles exposed to experimentally increased cort in ovo had a protracted decline in cort during the recovery phase of the stress response. All birds, regardless of treatment group, shifted to oxidative stress during an acute stress response. In addition, embryonic exposure to cort resulted in higher levels of reactive oxygen metabolites and an over-representation of short telomeres compared with the control birds. In many species, individuals with higher levels of oxidative stress and shorter telomeres have the poorest survival prospects. Given this, long-term costs of glucocorticoid-induced phenotypes may include accelerated ageing and increased mortality.

Mechanisms of airway obliteration after lung transplantation

Post-transplant bronchiolitis obliterans, also called bronchiolitis obliterans syndrome, affects up to 50-60% of patients who survive 5 yr after surgery according to its clinical definition, which is based on the degree of obstructive airway disease. Alloimmune-independent and -dependent mechanisms produce injuries and inflammation of epithelial cells and subepithelial structures, leading to aberrant tissue repair. The triggering of innate immunity by various infections or chemical injuries after, for example, gastroesophageal reflux, may lead to the release of danger signals that are able to activate dendritic cells, a crucial link with adaptive immunity. Inflammation can also increase the expression and display of major histocompatibility alloantigens and thus favor the initiation of rejection episodes. These phenomena may be limited in time and location or may be protracted. Reducing the risk of alloimmune-independent factors may be as important as treating acute episodes of lung rejection. Excessive immunosuppression may be deleterious by increasing the risk of infection, thereby triggering innate and adaptive immunity. New potential therapeutic targets are emerging from the research performed on leukotriene receptors, chemokine receptors, and growth factors. Neutralizing these molecules reduces the initial mononuclear and polynuclear infiltrates or the subsequent fibroproliferative process and the neovascular changes, feeding this process.

Robust postmortem survival of murine vestibular and cochlear stem cells

Potential treatment strategies of neurodegenerative and other diseases with stem cells derived from nonembryonic tissues are much less subjected to ethical criticism than embryonic stem cell-based approaches. Here we report the isolation of inner ear stem cells, which may be useful in cell replacement therapies for hearing loss, after protracted postmortem intervals. We found that neonatal murine inner ear tissues, including vestibular and cochlear sensory epithelia, display remarkably robust cellular survival, even 10 days postmortem. Similarly, isolation of sphere-forming stem cells was possible up to 10 days postmortem. We detected no difference in the proliferation and differentiation potential between stem cells isolated directly after death and up to 5 days postmortem. At longer postmortem intervals, we observed that the potency of sphere-derived cells to spontaneously differentiate into mature cell types diminishes prior to the cells losing their potential for self-renewal. Three-week-old mice also displayed sphere-forming stem cells in all inner ear tissues investigated up to 5 days postmortem. In summary, our results demonstrate that postmortem murine inner ear tissue is suited for isolation of stem cells.

Surfactant proteins SP-B and SP-C and their precursors in bronchoalveolar lavages from children with acute and chronic inflammatory airway disease

BACKGROUND: The surfactant proteins B (SP-B) and C (SP-C) are important for the stability and function of the alveolar surfactant film. Their involvement and down-regulation in inflammatory processes has recently been proposed, but their level during neutrophilic human airway diseases are not yet known. METHODS: We used 1D-electrophoresis and Western blotting to determine the concentrations and molecular forms of SP-B and SP-C in bronchoalveolar lavage (BAL) fluid of children with different inflammatory airway diseases. 21 children with cystic fibrosis, 15 with chronic bronchitis and 14 with pneumonia were included and compared to 14 healthy control children. RESULTS: SP-B was detected in BAL of all 64 patients, whereas SP-C was found in BAL of all but 3 children; those three BAL fluids had more than 80% neutrophils, and in two patients, who were re-lavaged later, SP-C was then present and the neutrophil count was lower. SP-B was mainly present as a dimer, SP-C as a monomer. For both qualitative and quantitative measures of SP-C and SP-B, no significant differences were observed between the four evaluated patient groups. CONCLUSION: Concentration or molecular form of SP-B and SP-C is not altered in BAL of children with different acute and chronic inflammatory lung diseases. We conclude that there is no down-regulation of SP-B and SP-C at the protein level in inflammatory processes of neutrophilic airway disease.

[Primary ciliary dyskinesia (Pcd) in Austria]

INTRODUCTION: Primary ciliary dyskinesia (PCD) is a rare hereditary recessive disease with symptoms of recurrent pneumonia, chronic bronchitis, bronchiectasis, and chronic sinusitis. Chronic rhinitis is often the presenting symptom in newborns and infants. Approximately half of the patients show visceral mirror image arrangements (situs inversus). In this study, we aimed 1) to determine the number of paediatric PCD patients in Austria, 2) to show the diagnostic and therapeutic modalities used in the clinical centres and 3) to describe symptoms of children with PCD. PATIENTS, MATERIAL AND METHODS: For the first two aims, we analysed data from a questionnaire survey of the European Respiratory Society (ERS) task force on Primary Ciliary Dyskinesia in children. All paediatric respiratory units in Austria received a questionnaire. Symptoms of PCD patients from Vienna Children's University Hospital (aim 3) were extracted from case histories. RESULTS: In 13 Austrian clinics 48 patients with PCD (36 aged from 0-19 years) were identified. The prevalence of reported cases (aged 0-19 yrs) in Austria was 1:48000. Median age at diagnosis was 4.8 years (IQR 0.3-8.2), lower in children with situs inversus compared to those without (3.1 vs. 8.1 yrs, p = 0.067). In 2005-2006, the saccharine test was still the most commonly used screening test for PCD in Austria (45%). Confirmation of the diagnosis was usually by electron microscopy (73%). All clinics treated exacerbations immediately with antibiotics, 73% prescribed airway clearance therapy routinely to all patients. Other therapies and diagnostic tests were applied very inconsistently across Austrian hospitals. All PCD patients from Vienna (n = 13) had increased upper and lower respiratory secretions, most had recurring airway infections (n = 12), bronchiectasis (n = 7) and bronchitis (n = 7). CONCLUSION: Diagnosis and therapy of PCD in Austria are inhomogeneous. Prospective studies are needed to learn more about the course of the disease and to evaluate benefits and harms of different treatment strategies.

[Antibiotic therapy in the outpatient setting: update 2009]

Rational outpatient therapy restricts antibiotics to infections where they are beneficial and selects substances based on local resistance patterns. Respiratory tract infections typically caused by viruses should not be treated with antibiotics (e.g., rhinitis, bronchitis, sinusitis). Many respiratory infections likely caused by bacteria can be treated with aminopenicillin, sometimes combined with a beta-lactamase inhibitor. Quinolones should be used only as exception for respiratory tract infections, since resistance is rising. For this reason uncomplicated urinary tract infections (cystitis) should be treated with trimethoprim-sulfa-methoxazole (TMP-SMX) instead of quinolones, even though approximately 20% of Escherichia coli are resistant to TMP-SMX. Skin and soft tissue infections are best treated with beta-lactam antibiotics, as long as the community acquired methicillin-resistant strains of S. aureus frequently seen in certain countries remain uncommon here.

A simple asthma prediction tool for preschool children with wheeze or cough

BACKGROUND Many preschool children have wheeze or cough, but only some have asthma later. Existing prediction tools are difficult to apply in clinical practice or exhibit methodological weaknesses. OBJECTIVE We sought to develop a simple and robust tool for predicting asthma at school age in preschool children with wheeze or cough. METHODS From a population-based cohort in Leicestershire, United Kingdom, we included 1- to 3-year-old subjects seeing a doctor for wheeze or cough and assessed the prevalence of asthma 5 years later. We considered only noninvasive predictors that are easy to assess in primary care: demographic and perinatal data, eczema, upper and lower respiratory tract symptoms, and family history of atopy. We developed a model using logistic regression, avoided overfitting with the least absolute shrinkage and selection operator penalty, and then simplified it to a practical tool. We performed internal validation and assessed its predictive performance using the scaled Brier score and the area under the receiver operating characteristic curve. RESULTS Of 1226 symptomatic children with follow-up information, 345 (28%) had asthma 5 years later. The tool consists of 10 predictors yielding a total score between 0 and 15: sex, age, wheeze without colds, wheeze frequency, activity disturbance, shortness of breath, exercise-related and aeroallergen-related wheeze/cough, eczema, and parental history of asthma/bronchitis. The scaled Brier scores for the internally validated model and tool were 0.20 and 0.16, and the areas under the receiver operating characteristic curves were 0.76 and 0.74, respectively. CONCLUSION This tool represents a simple, low-cost, and noninvasive method to predict the risk of later asthma in symptomatic preschool children, which is ready to be tested in other populations.

SerpinB1 deficiency is not associated with increased susceptibility to pulmonary emphysema in mice

Chronic obstructive pulmonary disease (COPD) is characterized by emphysema and chronic bronchitis and is a leading cause of morbidity and mortality worldwide. Tobacco smoke and deficiency in α1-antitrypsin (AAT) are the most prominent environmental and genetic risk factors, respectively. Yet the pathogenesis of COPD is not completely elucidated. Disease progression appears to include a vicious circle driven by self-perpetuating lung inflammation, endothelial and epithelial cell death, and proteolytic degradation of extracellular matrix proteins. Like AAT, serpinB1 is a potent inhibitor of serine proteases including neutrophil elastase and cathepsin G. Because serpinB1 is expressed in myeloid and lung epithelial cells and is protective during lung infections, we investigated the role of serpinB1 in preventing age-related and cigarette smoke-induced emphysema in mice. Fifteen-month-old mice showed increased lung volume and decreased pulmonary function compared with young adult mice (3 mo old), but no differences were observed between serpinB1-deficient (KO) and wild-type (WT) mice. Chronic exposure to secondhand cigarette smoke resulted in structural emphysematous changes compared with respective control mice, but no difference in lung morphometry was observed between genotypes. Of note, the different pattern of stereological changes induced by age and cigarette smoke suggest distinct mechanisms leading to increased airway volume. Finally, expression of intracellular and extracellular protease inhibitors were differently regulated in lungs of WT and KO mice following smoke exposure; however, activity of proteases was not significantly altered. In conclusion, we showed that, although AAT and serpinB1 are similarly potent inhibitors of neutrophil proteases, serpinB1 deficiency is not associated with more severe emphysema.

Relaxation in hypertrophic cardiomyopathy and hypertensive heart disease: relations between hypertrophy and diastolic function

AIM To determine the relation between the extent and distribution of left ventricular hypertrophy and the degree of disturbance of regional relaxation and global left ventricular filling. METHODS Regional wall thickness (rWT) was measured in eight myocardial regions in 17 patients with hypertrophic cardiomyopathy, 12 patients with hypertensive heart disease, and 10 age matched normal subjects, and an asymmetry index calculated. Regional relaxation was assessed in these eight regions using regional isovolumetric relaxation time (rIVRT) and early to late peak filling velocity ratio (rE/A) derived from Doppler tissue imaging. Asynchrony of rIVRT was calculated. Doppler left ventricular filling indices were assessed using the isovolumetric relaxation time, the deceleration time of early diastolic filling (E-DT), and the E/A ratio. RESULTS There was a correlation between rWT and both rIVRT and rE/A in the two types of heart disease (hypertrophic cardiomyopathy: r = 0.47, p < 0.0001 for rIVRT; r = -0.20, p < 0.05 for rE/A; hypertensive heart disease: r = 0.21, p < 0.05 for rIVRT; r = -0.30, p = 0.003 for rE/A). The degree of left ventricular asymmetry was related to prolonged E-DT (r = 0. 50, p = 0.001) and increased asynchrony (r = 0.42, p = 0.002) in all patients combined, but not within individual groups. Asynchrony itself was associated with decreased E/A (r = -0.39, p = 0.01) and protracted E-DT (r = 0.69, p < 0.0001) and isovolumetric relaxation time (r = 0.51, p = 0.001) in all patients. These correlations were still significant for E-DT in hypertrophic cardiomyopathy (r = 0.56, p = 0.02) and hypertensive heart disease (r = 0.59, p < 0.05) and for isovolumetric relaxation time in non-obstructive hypertrophic cardiomyopathy (n = 8, r = 0.87, p = 0.005). CONCLUSIONS Non-invasive ultrasonographic examination of the left ventricle shows that in both hypertrophic cardiomyopathy and hypertensive heart disease, the local extent of left ventricular hypertrophy is associated with regional left ventricular relaxation abnormalities. Asymmetrical distribution of left ventricular hypertrophy is indirectly related to global left ventricular early filling abnormalities through regional asynchrony of left ventricular relaxation.

Health of farmed fish: its relation to fish welfare and its utility as welfare indicator

This brief review focuses on health and biological function as cornerstones of fish welfare. From the function-based point of view, good welfare is reflected in the ability of the animal to cope with infectious and non-infectious stressors, thereby maintaining homeostasis and good health, whereas stressful husbandry conditions and protracted suffering will lead to the loss of the coping ability and, thus, to impaired health. In the first part of the review, the physiological processes through which stressful husbandry conditions modulate health of farmed fish are examined. If fish are subjected to unfavourable husbandry conditions, the resulting disruption of internal homeostasis necessitates energy-demanding physiological adjustments (allostasis/acclimation). The ensuing energy drain leads to trade-offs with other energy-demanding processes such as the functioning of the primary epithelial barriers (gut, skin, gills) and the immune system. Understanding of the relation between husbandry conditions, allostatic responses and fish health provides the basis for the second theme developed in this review, the potential use of biological function and health parameters as operational welfare indicators (OWIs). Advantages of function- and health-related parameters are that they are relatively straightforward to recognize and to measure and are routinely monitored in most aquaculture units, thereby providing feasible tools to assess fish welfare under practical farming conditions. As the efforts to improve fish welfare and environmental sustainability lead to increasingly diverse solutions, in particular integrated production, it is imperative that we have objective OWIs to compare with other production forms, such as high-density aquaculture. However, to receive the necessary acceptance for legislation, more robust scientific backing of the health- and function-related OWIs is urgently needed.

Core formation and mantle differentiation on Mars

Geochemical investigation of Martian meteorites (SNC meteorites) yields important constraints on the chemical and geodynamical evolution of Mars. These samples may not be representative of the whole of Mars; however, they provide constraints on the early differentiation processes on Mars. The bulk composition of Martian samples implies the presence of a metallic core that formed concurrently as the planet accreted. The strong depletion of highly siderophile elements in the Martian mantle is only possible if Mars had a large scale magma ocean early in its history allowing efficient separation of a metallic melt from molten silicate. The solidification of the magma ocean created chemical heterogeneities whose ancient origin is manifested in the heterogeneous 142Nd and 182W abundances observed in different meteorite groups derived from Mars. The isotope anomalies measured in SNC meteorites imply major chemical fractionation within the Martian mantle during the life time of the short-lived isotopes 146Sm and 182Hf. The Hf-W data are consistent with very rapid accretion of Mars within a few million years or, alternatively, a more protracted accretion history involving several large impacts and incomplete metal-silicate equilibration during core formation. In contrast to Earth early-formed chemical heterogeneities are still preserved on Mars, albeit slightly modified by mixing processes. The preservation of such ancient chemical differences is only possible if Mars did not undergo efficient whole mantle convection or vigorous plate tectonic style processes after the first few tens of millions of years of its history.

Effect of Acute Administration of Angiopoietin-1 in Experimental Traumatic Spinal Cord Injury: Magnetic Resonance Imaging and Neurobehavioral Studies

Spinal cord injury (SCI) is a devastating condition that affects people in the prime of their lives. A myriad of vascular events occur after SCI, each of which contributes to the evolving pathology. The primary trauma causes mechanical damage to blood vessels, resulting in hemorrhage. The blood-spinal cord barrier (BSCB), a neurovascular unit that limits passage of most agents from systemic circulation to the central nervous system, breaks down, resulting in inflammation, scar formation, and other sequelae. Protracted BSCB disruption may exacerbate cellular injury and hinder neurobehavioral recovery in SCI. In these studies, angiopoietin-1 (Ang1), an agent known to reduce vascular permeability, was hypothesized to attenuate the severity of secondary injuries of SCI. Using longitudinal magnetic resonance imaging (MRI) studies (dynamic contrast-enhanced [DCE]-MRI for quantification of BSCB permeability, highresolution anatomical MRI for calculation of lesion size, and diffusion tensor imaging for assessment of axonal integrity), the acute, subacute, and chronic effects of Ang1 administration after SCI were evaluated. Neurobehavioral assessments were also performed. These non-invasive techniques have applicability to the monitoring of therapies in patients with SCI. In the acute phase of injury, Ang1 was found to reduce BSCB permeability and improve neuromotor recovery. Dynamic contrast-enhanced MRI revealed a persistent compromise of the BSCB up to two months post-injury. In the subacute phase of injury, Ang1’s effect on reducing BSCB permeability was maintained and it was found to transiently reduce axonal integrity. The SCI lesion burden was assessed with an objective method that compared favorably with segmentations from human raters. In the chronic phase of injury, Ang1 resulted in maintained reduction in BSCB permeability, a decrease in lesion size, and improved axonal integrity. Finally, longitudinal correlations among data from the MRI modalities and neurobehavioral assays were evaluated. Locomotor recovery was negatively correlated with lesion size in the Ang1 cohort and positively correlated with diffusion measures in the vehicle cohort. In summary, the results demonstrate a possible role for Ang1 in mitigating the secondary pathologies of SCI during the acute and chronic phases of injury.