[Physical activity and pulmonary rehabilitation in adults with asthma]. / Apports de l'activité physique et de la réadaptation respiratoire dans l'asthme de l'adulte.

Physical activity is reduced in people with asthma compared to the general population, especially in situations where patients have uncontrolled asthma symptoms, persistent airflow obstruction and other long-term medical problems, in particular obesity and anxiety. Exertional dyspnea, which is of multifactorial origin, is the main cause of reduced physical activity reduction and draws patients into a vicious circle further impairing quality of life and asthma control. Both the resumption of a regular physical activity, integrated into daily life, adapted to patients' needs and wishes as well as physical and environmental possibilities for mild to moderate asthmatics, and pulmonary rehabilitation (PR) for severe and/or uncontrolled asthmatics, improve control of asthma, dyspnea, exercise tolerance, quality of life, anxiety, depression and reduce exacerbations. A motivational interview to promote a regular programme of physical activity in mild to moderate asthma (steps 1 to 3) should be offered by all health professionals in the patient care pathway, within the more general framework of therapeutic education. The medical prescription of physical activities, listed in the Public Health Code for patients with long-term diseases, and pulmonary rehabilitation should be performed more often by specialists or the attending physician. Pulmonary rehabilitation addresses the needs of severe asthma patients (steps 4 and 5), and of any asthmatic patient with poorly controlled disease and/or requiring hospitalized for acute exacerbations, regardless of the level of airflow obstruction, and/or with associated comorbidities, and before prescribing biological therapies.

Point-of-care Hepatitis C virus testing and linkage to treatment in an Australian inner-city emergency department.

BACKGROUND: In Australia, Hepatitis C Virus (HCV) treatment is declining, despite broad access to direct-acting antiviral medication. People who inject drugs are proportionally over-represented in emergency department presentations. Emergency department assessment of people who have injected drugs for HCV presents an opportunity to engage this marginalised population with treatment. We describe the outcomes of risk-based screening and point-of-care anti-HCV testing for emergency department patients, and linkage to outpatient antiviral treatment. METHODS: During the three-month study period, consecutive adult patients who presented to the emergency department during the study times were screened for risk factors and offered the OraQuick oral HCV antibody test. Those with reactive results were offered venepuncture in the emergency department for confirmatory testing and direct-acting antiviral treatment in clinic. The main outcome measures were the number and proportion of viremic participants that were linked to the hepatitis clinic, commenced treatment and achieved a sustained viral response. Secondary outcome measures were the proportion (%) of presentations screened that were oral antibody reactive, and the prevalence and type of HCV risk factors. RESULTS: During the study period, 2408 of the 3931 (61%) presentations to the emergency department were eligible for screening. Of these 2408 patients, 1122 (47%) participated, 307 (13%) declined participation and 977 (41%) could not be approached during their time in the emergency department. Among the 1122 participants, 378 (34%) reported at least one risk factor. Subsequently, 368 (97%) of the 378 participants underwent OraQuick anti-HCV test, and 50 (14%) had a reactive result. A risk factor of ever having injected drugs was present in 44 (88%) of participants who were sero-positive. Of the 45 that had blood tested, 30 (67%) were HCV ribonucleic acid (RNA) positive. Three participants died. Of the 27 remaining participants, 10 (37%) commenced treatment and 7 of these 10 (70%) obtained a cure. There was a high rate of homelessness (24%) among anti-HCV positive participants. CONCLUSION: Among emergency department participants with a risk factor for HCV, positive serology was common using a rapid point-of-care test. A history of injecting drug use was identified as the risk factor with highest yield for positive HCV serology, and is suitable as a single screening question. However, linkage to care post ED presentation was low in this marginalised population. There is a need for new pathways to improve the care cascade for marginalised individuals living with HCV infection.

Emergence of Aspergillus fumigatus azole resistance in azole-naïve patients with chronic obstructive pulmonary disease and their homes.

Azole-resistant Aspergillus fumigatus (ARAF) has been reported in patients with chronic obstructive pulmonary disease (COPD) but has not been specifically assessed so far. Here, we evaluated ARAF prevalence in azole-naïve COPD patients and their homes, and assessed whether CYP51A mutations were similar in clinical and environmental reservoirs. Sixty respiratory samples from 41 COPD patients with acute exacerbation and environmental samples from 36 of these patient's homes were prospectively collected. A. fumigatus was detected in respiratory samples from 11 of 41 patients (27%) and in 15 of 36 domiciles (42%). Cyp51A sequencing and selection on itraconazole medium of clinical (n = 68) and environmental (n = 48) isolates yielded ARAF detection in 1 of 11 A. fumigatus colonized patients with COPD (9%) and 2 of 15 A. fumigatus-positive patient's homes (13%). The clinical isolate had no CYP51A mutation. Two environmental isolates from two patients harbored TR34 /L98H mutation, and one had an H285Y mutation. Coexistence of different cyp51A genotypes and/or azole resistance profiles was detected in 3 of 8 respiratory and 2 of 10 environmental samples with more than one isolate, confirming the need for a systematic screening of all clinically relevant isolates. The high prevalence of ARAF in patients with COPD and their homes supports the need for further studies to assess the prevalence of azole resistance in patients with Aspergillus diseases in Northern France.

[Effects of an educational program in non-adherent apneic patients treated with continuous positive airway pressure]. / Éducation thérapeutique de patients apnéiques inobservants sous pression positive continue.

INTRODUCTION: Obstructive Sleep Apnea (OSA) is a chronic, frequent pathology impacting patients' quality of life. Continuous positive airways pressure (CPAP) is the most effective treatment, but is often considered binding and thus poorly observed. The aim of this study was to assess the impact of an educational program in non-adherent patients with OSA, to identify the factors of inobservance and to determine risk groups. PATIENTS AND METHODS: We enrolled 21 patients presenting OSA in this monocentric, forward-looking study. Nineteen patients completed the study. The inclusion criterion was a daily observance less than 4 hours a night. Educational program was realized by a specialized, trained team, with the authorization of the Regional Agency of Health. RESULTS: Our population consisted of 15 male and six female, all of them obese, with a medium age of 57.7 ± 12.9 years, treated for 10,7 ± 15 months. All of our patients had few symptoms. After the educational program, two groups were individualized according to their observance. Fifty-two percent of patients became compliant to CPAP treatment. Demographic data and medical histories did not differ between these two groups: nine patients remained inobservant (medium daily treatment duration of 57 ± 49 minutes); ten patients became observant (medium daily treatment duration raising from 104 ± 70 minutes to 322 ± 65 minutes, P=0.0002). Among these ten patients, seven were considered as having accepted their disease at initial educational diagnosis. CONCLUSION: The educational program improved adherence to CPAP treatment in 52% of our patients. All included patients had few symptoms. This could raise the issue of a poorer perception of treatment efficacy in less symptomatic patients. Disease acceptance also appeared linked to CPAP treatment compliance.

[Idiopathic pulmonary fibrosis and sleep disorders]. / Fibrose pulmonaire idiopathique et troubles du sommeil.

Idiopathic pulmonary fibrosis (IPF) is the most common interstitial lung disease. Despite progress made in understanding the pathophysiological mechanisms behind the development of the disease, its prognosis is poor. For this reason, any measure to improve the quality of life for these patients should be preferred. Some authors are interested in sleep disorders, and possible impact on quality of life. Patients with IPF have lowered scores of quality of life compared to those found in general population, with some correlation with the scores of sleep quality. There is a hyperfragmentation with many arousals and desaturation events. Some authors also report an apnea-hypopnea index higher in these patients, but these data are not found in all the studies. Correcting these obstructive phenomena may have a beneficial effect on survival, which would make systematic the sleep assessment in these patients. Finally, the relationship between IPF, gastroesophageal reflux and sleep apnea syndrome remains unclear.

Embodied linearity of speed control in Drosophila melanogaster.

Fruitflies regulate flight speed by adjusting their body angle. To understand how low-level posture control serves an overall linear visual speed control strategy, we visually induced free-flight acceleration responses in a wind tunnel and measured the body kinematics using high-speed videography. Subsequently, we reverse engineered the transfer function mapping body pitch angle onto flight speed. A linear model is able to reproduce the behavioural data with good accuracy. Our results show that linearity in speed control is realized already at the level of body posture-mediated speed control and is therefore embodied at the level of the complex aerodynamic mechanisms of body and wings. Together with previous results, this study reveals the existence of a linear hierarchical control strategy, which can provide relevant control principles for biomimetic implementations, such as autonomous flying micro air vehicles.

Aerodynamic damping during rapid flight maneuvers in the fruit fly Drosophila.

We systematically investigated the effect of body rotation on the aerodynamic torque generation on flapping wings during fast turning maneuvers (body saccades) in the fruit fly Drosophila. A quasi-steady aerodynamic simulation of turning maneuvers with symmetrically flapping wings showed that body rotation causes a substantial aerodynamic counter-torque, known as flapping counter-torque (FCT), which acts in the opposite direction to turning. Simulation results further indicate that FCTs are linearly dependent on the rotational velocity and the flapping frequency regardless of the kinematics of wing motion. We estimated the damping coefficients for the principal rotation axes - roll, pitch, yaw - in the stroke plane frame. FCT-induced passive damping exists about all the rotation axes examined, suggesting that the effects of body rotation cannot be ignored in the analysis of free-flight dynamics. Force measurements on a dynamically scaled robotic wing undergoing realistic saccade kinematics showed that although passive aerodynamic damping due to FCT can account for a large part of the deceleration during saccades, active yaw torque from asymmetric wing motion is required to terminate body rotation. In addition, we calculated the mean value of the damping coefficient at 21.00 x10(-12) N m s based on free-flight data of saccades, which is somewhat lower than that estimated by the simulation results (26.84 x 10(-12) N m s).

Altered glycosylation of proteins in cancer: what is the potential for new anti-tumour strategies.

It is becoming increasingly apparent that cell surface oligosaccharides play pivotal roles as recognition molecules in a range of cell communication and adhesion processes. Alterations in cellular glycosylation are also associated with diseases, including cancer, and may have functional significance. This paper gives an overview of the complex topic of cellular glycosylation mechanisms and reviews the well-documented alterations in cellular glycosylation of proteins in malignancy. One particular type of cancer-associated glycosylation change, the incomplete synthesis of O-linked glycans, is highlighted, and its possible functional significance in cancer cell metastatic mechanisms is discussed. The significance that cancer-associated changes in glycoprotein glycosylation may have in new approaches to anti-tumour therapies is explored.

Effects of oxygen on exercise-induced increase of pulmonary arterial pressure in idiopathic pulmonary fibrosis.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a severe disease with no known effective therapy. Patients with IPF may develop severe increase of pulmonary arterial pressure (PAP) on exercise, the mechanisms of which is not clearly identified. OBJECTIVES: To determine whether oxygen may correct the increase of PAP developed during exercise in patients with IPF. PATIENTS AND METHODS: We performed a prospective study on patients with IPF and no hypoxaemia at rest. The absence of pulmonary hypertension (PH) at rest was confirmed by echocardiography (systolic PAP <35 mmHg). Eight patients underwent echocardiography during exercise in air and with oxygen (to maintain saturation of at least 94%). Right ventricle-right atrium gradient and cardiac output were measured at rest, after each increment and at peak. We then compared the echocardiographic results obtained for air and oxygen. RESULTS: All patients developed significant increase of SPAP on exercise (73 +/- 14 mmHg in air). Oxygen did not significantly improve SPAP on exercise (SPAP: 76 +/- 15 mmHg). Echocardiographic characteristics were similar between air and oxygen except for exercise tolerance in term of workload (p=0.045) and endurance (p=0.017). Resting pulmonary function tests did not predict the occurrence of increase of PAP on exercise. CONCLUSION: Our results demonstrate that oxygen does not improve exercise-induced increase of PAP in patients with IPF and support the hypothesis that hypoxic vaso-constriction is not the main mechanism of acute increase of PAP during exercise.

Modulation of immune response in mice immunised with an inactivated Salmonella vaccine and gavaged with Andrographis paniculata extract or andrographolide.

Gavage of mice, immunised with an inactivated S. typhimurium vaccine, with Andrographis paniculata extract [APE] or andrographolide [AND] resulted in an enhancement of Salmonella-specific antibody response and induction of cell-mediated response against salmonellosis. Mice were vaccinated with either one or two doses of killed S. typhimurium vaccine and fed two different quantities of APE or AND, for 14 days in mice immunised with one dose of the vaccine, and for 28 days in mice immunised with two doses of vaccine, respectively. Both APE and AND were found to enhance IgG antibody levels against S. typhimurium, the enhancement being statistically significant in mice receiving two doses of the vaccine. Splenocyte cultures, prepared from mice immunised with the killed Salmonella vaccine and treated with APE or AND, showed a remarkable increase in the production IFN-gamma following stimulation with the bacterial lysate, indicating an induction of Salmonella-specific cell-mediated response/immune response.

Look and turn: landmark-based goal navigation in honey bees.

This report describes the piloting mechanisms employed by honey bees during their final approach to a goal. Conceptually applying a bottom-up approach, we systematically varied the position, number and appearance landmarks associated with a rewarded target location within a large, homogenous flight tent. The flight behavior measured under various conditions is well explained with visuo-motor control loops that link perceived landmarks with appropriate turning responses. This view is consistent with the requirement of prolonged reinforcement learning for efficient goal navigation. A simple model is able to provide a comprehensive explanation for diverse flight patterns that range from convoluted searching behavior to highly idiosyncratic approaches, depending on the experimental context. Our results challenge the prevalent notion that honey bees employ image matching for visual guidance toward a goal site. Basic visuo-motor control loops may better meet the high demands for robust and fast flight control, which could serve as a powerful bio-mimetic design principle for micro-robotic aircraft.

The cell wall-modifying xyloglucan endotransglycosylase/hydrolase LeXTH1 is expressed during the defence reaction of tomato against the plant parasite Cuscuta reflexa.

A suppressive subtractive hybridization technique was used to identify genes, which were induced during the early phases of the interaction between dodder (Cuscuta reflexa), a phanerogamic parasite, and its incompatible host plant tomato. One of the identified genes encodes a tomato xyloglucan endotransglycosylase/hydrolase (XTH)--an enzyme involved in cell wall elongation and restructuring. The corresponding LeXTH1 mRNA accumulated 6 h after attachment of the parasite. In contrast, wounding did not influence the expression level. Subsequent to LeXTH1 mRNA accumulation, an increase in XTH activity at the infection sites as well as in adjacent tissues was observed. The effect of IAA on LeXTH1 expression was analyzed because the concentration of this phytohormone is known to increase in the tomato tissue during the interaction with the parasite. LeXTH1 mRNA accumulation was in fact induced by external application of auxin. However, in the auxin-insensitive tomato mutant diageotropica, Cuscuta induced LeXTH1-mRNA accumulated with a time course similar to wild type tomato. Thus, auxin appears not to be an essential signal for infection-induced LeXTH1 activation. Our data suggest a role for xyloglucan transglycosylation in defence reactions associated with the incompatible tomato- Cuscuta interaction.

Context-dependent stimulus presentation to freely moving animals in 3D.

The presentation of controllable, dynamic sensory stimuli provides a powerful experimental paradigm, which has been extensively applied to explore sensory processing in walking and tethered flying insects. Recent advances in computer hardware and software technology provide the opportunity to track the 3D flight path of free-flying insects and process these data in real-time, opening up the possibility to present dynamic stimuli to free-flying animals. To accommodate for the increased complexity relating to 3D space, we partitioned experimental design, real-time data acquisition and stimulus control into multiple self-contained modules. 3D experimental scenarios were created in a stand-alone application by forging multiple 3D space-stimulus relationships. The use of dynamic cues is illustrated by an experiment, in which dynamic acoustic cues were presented to a free-flying parasitoid fly in a large 3D environment. The combination of loosely coupled modules provides robust and flexible solutions, allowing new paradigms to be readily implemented based on existing technologies. We demonstrate this with a test system that displayed a complex visual stimulus, controlled in real-time by the 2D position and orientation of a test object. The presented methods are applicable in a variety of novel experimental paradigms, including learning paradigms, for various sensory modalities in walking, swimming and flying animals.

Drosophila flight force measurements using a MEMS micro force sensor.

This paper reports a MEMS micro force sensor with differential tri-plate comb drives. Bulk micromachining is utilized to construct the high aspect ratio devices. The sensor has a high sensitivity, good linearity, and a large bandwidth, which are required for characterizing flight behavior of fruit flies (Drosophila). The technique allows instantaneous flight forces, which result from the combination of aerodynamic forces and inertial forces, to be captured in real time, providing valuable data for understanding flight biomechanics in Drosophila. The integration of the MEMS micro force sensors into flight simulators will provide a novel and efficient experimental paradigm for further insect neurophysiology studies. The potential impact of this research extends beyond gathering flight data on Drosophila by demonstrating how MEMS technology can be used to provide valuable tools for biological investigations.

Xyloglucan endotransglucosylase action is high in the root elongation zone and in the trichoblasts of all vascular plants from Selaginella to Zea mays.

The endotransglucosylase action of the enzyme xyloglucan endotransglucosylase/hydrolase (XTH) was localized in the roots of diverse vascular plants: club-mosses (lycopodiophytes), ferns, gymnosperms, monocots, and dicots. High action was always found in the epidermis cell wall of the elongation zone and in trichoblasts in the differentiation zone. Clearly XTH and its action in root development evolved before the evolutionary divergence of ferns and seed plants and also of the lycopodiophytes and euphyllophytes.

Root hair initiation is coupled to a highly localized increase of xyloglucan endotransglycosylase action in Arabidopsis roots.

Root hairs are formed by two separate processes: initiation and subsequent tip growth. Root hair initiation is always accompanied by a highly localized increase in xyloglucan endotransglycosylase (XET) action at the site of future bulge formation, where the trichoblast locally loosens its cell wall. This suggests an important role of XET in the first stages of root hair initiation. The tip of growing root hairs is not marked by localized high XET action. Experiments in which root hair initiation was modulated and observations on root hair mutants support this view. The ethylene precursor 1-aminocyclopropane-1-carboxylic acid shifts both root hair initiation and the local increase in XET action toward the root tip. On the other hand, roots treated with the ethylene inhibitor aminoethoxyvinyl-glycine, as well as roots of mutants affected in root hair initiation (rhl1, rhd6-1, and axr2-1) revealed no localized increases of XET action at all and consequently did not initiate root hairs. Disruption of actin and microtubules did not prevent the localized increase in XET action. Also, the temporal and spatial pattern of action as the specific pH dependence suggest that different isoforms of XET act in different processes of root development.

The development and psychometric evaluation of the Ethical Issues Scale.

PURPOSE: To describe the Ethical Issues Scale (EIS), its conceptual development and psychometric evaluation, and its uses in determining how frequently nurses experience ethical issues in practice. DESIGN: The EIS was validated with a sample (N = 2,090) of New England registered nurses (RNs) currently in practice. The sample was randomly split into two approximately equal samples. The calibration sample was used to derive the underlying components; the validation sample was used to confirm the component structure. METHODS: Psychometric analysis of the 35-item EIS included: (a) item analysis, (b) confirmatory principal components analysis (PCA), and (c) internal consistency reliability using Cronbach's alpha. RESULTS: Three components (end-of-life-treatment issues, patient care issues, and human rights issues) were demonstrated, confirming the original conceptually-derived structure. The calibration sample accounted for 42.4% of initially extracted common variance; the validation sample accounted for 41.5% of initially extracted common variance. CONCLUSIONS: The three EIS subscales had satisfactory internal consistency reliability and factorial validity for use as independent scales in future studies.

Density-labelling of cell wall polysaccharides in cultured rose cells: comparison of incorporation of 2H and 13C from exogenous glucose.

Labelling with stable isotopes has under-exploited potential for studies of polysaccharide endotransglycosylation in vivo. Ideally, the labelled polysaccharides should have the highest possible buoyant density. Although [13C6]glucose has previously been used as a precursor, it was unclear whether 2H would be efficiently incorporated from [2H]glucose or lost as D2O. Rose (Rosa sp.) cell-suspension cultures efficiently incorporated 13C from D-[13C6,2H7]glucose into wall polysaccharides with negligible dilution from atmospheric 12CO2. Also, approximately 70% of the 2H atoms in D-[13C6,2H7]glucose were retained during polysaccharide biosynthesis. This shows that relatively few cycles of intermediary metabolism leading to the release of D2O occurred before sugar residues were incorporated into wall polysaccharides. In agreement with these observations, isopycnic centrifugation in caesium trifluoroacetate gradients showed that the hydrated buoyant density of xyloglucan synthesised by rose cells growing on [13C6,2H7]glucose and [13C6]glucose was 3.7 and 2.6% higher, respectively, than in isotopically non-labelled cultures. Thus, [13C,2H]glucose-feeding enabled a 42% better resolution of 'heavy' from 'light' xyloglucan than [13C]glucose-feeding.

Characteristics of xyloglucan after attack by hydroxyl radicals.

It has been proposed that plant cell-wall polysaccharides are subject in vivo to non-enzymic scission mediated by hydroxyl radicals (-*OH). In the present study, xyloglucan was subjected in vitro to partial, non-enzymic scission by treatment with ascorbate plus H(2)O(2), which together generate -*OH. The partially degraded xyloglucan appeared to contain ester bonds within the backbone, as indicated by an irreversible decrease in viscosity upon alkaline hydrolysis. Aldehyde and/or ketone groups were also introduced into the polysaccharide by -*OH-attack, as indicated by staining with aniline hydrogen-phthalate and by reaction with NaB(3)H(4). The introduction of ester and oxo groups supports the proposed sequence of reactions: (a) -*OH-mediated H-abstraction to produce a carbon-centred carbohydrate radical; (b) reaction of the latter with O(2); and (c) elimination of a hydroperoxyl radical (HO(2)*-). When the partially degraded xyloglucan was reduced with NaB(3)H(4) followed by acid hydrolysis, several 3H-aldoses were detected ([3H]galactose, [3H]xylose, [3H]glucose, [3H]ribose and probably [3H]mannose), in addition to unidentified 3H-products (probably including anhydroaldoses). 3H-Alditols were undetectable, showing that few or no conventional reducing termini were introduced. Digestion of the NaB(3)H(4)-reduced, partially degraded xyloglucan with Driselase released 25 times more [3H]Xyl-alpha-(1-->6)-Glc than Xyl-alpha-(1-->6)-[3H]Glc, suggesting that the xylose side-chains of the xyloglucan had been more heavily attacked by -*OH than the glucose residues of the backbone. The radioactive xyloglucan was readily digested by cellulase, yielding 3H-products in the hepta- to nonasaccharide range. A fingerprinting strategy for identifying -*OH-attacked xyloglucan in plant cell walls is proposed.

Fingerprinting of polysaccharides attacked by hydroxyl radicals in vitro and in the cell walls of ripening pear fruit.

Hydroxyl radicals (*OH) may cause non-enzymic scission of polysaccharides in vivo, e.g. in plant cell walls and mammalian connective tissues. To provide a method for detecting the action of endogenous *OH in vivo, we investigated the products formed when polysaccharides were treated with *OH (generated in situ by ascorbate-H(2)O(2)-Cu(2+) mixtures) followed by NaB(3)H(4). Treatment with *OH increased the number of NaB(3)H(4)-reacting groups present in citrus pectin, homogalacturonan and tamarind xyloglucan. This increase is attributed partly to the formation of glycosulose and glycosulosuronic acid residues, which are then reduced back to the original (but radioactive) sugar residues and their epimers by NaB(3)H(4). The glycosulose and glycosulosuronic acid residues were stable for >16 h at 20 degrees C in ethanol or buffer (pH 4.7), but were destroyed in alkali. Driselase-digestion of the radiolabelled polysaccharides yielded characteristic patterns of (3)H-products, which included galactose and galacturonate from pectin, and isoprimeverose, galactose, glucose and arabinose from xyloglucan. Pectin yielded at least eight (3)H-labelled anionic products, separable by electrophoresis at pH 3.5. The patterns of radioactive products form useful 'fingerprints' by which *OH-attacked polysaccharides may be recognized. Applied to the cell walls of ripening pear (Pyrus communis) fruit, the method gave evidence for progressive *OH radical attack on polysaccharides during the softening process.