[The effects of hypnosis by virtual reality on tolerance to flexible bronchoscopy]. / Effets de l'hypnose par réalité virtuelle sur la tolérance de la bronchoscopie flexible.

INTRODUCTION: Patients often perceive flexible bronchoscopy as an unpleasant procedure. The aim of this study was to investigate the effect of virtual reality (VR) hypnosis on tolerance to flexible bronchoscopy. MATERIALS AND METHODS: We conducted a prospective, randomized, controlled, monocentric study comparing flexible bronchoscopy with VR-induced hypnosis to the usual procedure. Patient tolerance was evaluated using a visual analogue scale (VAS), the state-trait anxiety inventory (STAI) before and after the procedure and, finally, willingness to repeat the examination under the same conditions (WTR). RESULTS: Among the 70 patients included, 34 were randomized to the VR hypnosis group and 36 to the control group. There was no difference between the 2 groups in terms of modification of the pre-/post-bronchoscopy VAS for anxiety, pain, cough, choking, nausea and overall discomfort, or modification of the STAI score and WTR. Subgroup analysis among patients who were more anxious before the procedure revealed a trend toward reduced anxiety in the VR hypnosis group. CONCLUSION: This study did not observe any effect of VR hypnosis on the tolerance of patients during routine flexible bronchoscopy. However, VR hypnosis may be beneficial in patients with higher anxiety score before bronchoscopy, a hypothesis that needs to be confirmed by further studies with a larger number of subjects.

Intra- and inter-spatial variability of meiofauna in hadal trenches is linked to microbial activity and food availability.

Hadal trenches are depocenters for organic material, and host intensified benthic microbial activity. The enhanced deposition is presumed to be reflected in elevated meiofaunal standing-stock, but available studies are ambiguous. Here, we investigate the distribution of meiofauna along the Atacama Trench axis and adjacent abyssal and bathyal settings in order to relate the meiofauna densities to proxies for food availability. Meiofauna densities peaked at the sediment surface and attenuated steeply with increasing sediment depth. The distribution mirrored the vertical profile of the microbial-driven oxygen consumption rate demonstrating a close linkage between microbial activity and meiofauna density. Meiofaunal standing-stock along the trench axis varied by a factor of two, but were markedly higher than values from the abyssal site at the oceanic plate. Overall, meiofaunal densities poorly correlated with common proxies for food availability such as total organic carbon and phytopigments, but strongly correlated with the microbial benthic O2 consumption rate. We argue that microbial biomass likely represents an important meiofaunal food source for hadal meiofauna. Observations from three trench systems underlying surface water of highly different productivity confirmed elevated meiofaunal densities at the trench axis as compared to abyssal sites on oceanic plates. Food availability appear to drive elevated abundance and variations in meiofauna densities in hadal sediments.

Validation of the Wii Balance Board to assess balance modifications induced by increased respiratory loads in healthy subjects.

BACKGROUND: There is a link between breathing and balance and posture. When the inspiratory loads are increased by pathologies, there is a decrease of postural control. The increase of the inspiratory load on respiratory muscles is a common feature in various chronic pulmonary pathologies. Consequently, the balance of those patients is likely affected. RESEARCH QUESTION: The aim of this study is to validate the use of the Nintendo Wii Balance Board (WBB) to assess balance modifications induced by increased respiratory loads in healthy subjects. METHODS: Thirty-seven healthy young participants (25 ± 4 years old, 17 women) participated in this study. Five different conditions were tested: without anything (control), throughout a mouthpiece, and throughout three inspiratory threshold loads (ITL) at 10% (low), 40% (mid) and 60% (high) of the maximal inspiratory pressure. Each trial lasted for 60 s. Nine parameters were extracted based on center of pressure displacement based on a previously-validated method. ANOVA tests were used to compare the different conditions followed by Bonferroni's corrections. RESULTS: Highly statistically significant differences (all p < 0.01) and large effect sizes (all ω2 > 0.24) were obtained for all parameters between the different loads and the mouthpiece condition. There is a linear relationship between the load and balance perturbation. SIGNIFICANCE: In this study, we demonstrated the validity of the WBB to detect the effect of the inspiratory load on balance in young healthy subjects. Further studies are needed to determine if such a kind of evaluation can be used in clinics with patients suffering from chronic respiratory disease.

[Lung cancer screening and endoscopic approach of the pulmonary nodule]. / Dépistage du cancer du poumon et approche endoscopique du nodule pulmonaire.

Lung cancer screening corresponds to any investigation carried out to detect the presence of this type of cancer before the appearance of any symptomatology. According to the results of a large multicenter study in the US (NLST), American scientific societies are currently recommending the use of the CT Thoracic Scanner with a low dose of irradiation once a year for lung cancer screening in high-risk populations. European expert groups, for the most part, reserve their recommendations after publication of the results of a major European study (NELSON). As a corollary of screening campaigns, the management of lung nodules is likely to be more and more frequent in the targeted populations. This can be performed in different ways ranging from the less invasive, the CT Scanner follow-up, to the more invasive, the surgical resection. The endoscopic approach of the pulmonary nodule, whose results were so far limited, is actually regaining interest due to the contribution of new technologies in bronchial endoscopy.

Le dépistage du cancer du poumon correspond à toute investigation réalisée dans le but de détecter l'existence de ce type de cancer avant l'apparition de la moindre symptomatologie. Faisant suite à la publication d'une grande étude multicentrique aux USA (NLST), les sociétés savantes américaines recommandent actuellement l'utilisation du CT Scanner Thoracique à faible dose d'irradiation à raison d'une fois par an pour le dépistage du cancer du poumon dans les populations à risque. Les sociétés européennes, pour la plupart, réservent quant à elles leurs recommandations pour après la publication des résultats d'une grande étude européenne (NELSON). Corollaire des campagnes de dépistage, la prise en charge des nodules pulmonaires risque d'être de plus en plus fréquente dans les populations ciblées. Celle-ci peut être réalisée de différentes façons allant de la moins invasive, le suivi par CT Scanner, à la plus invasive, la chirurgie d'exérèse. L'approche endoscopique du nodule pulmonaire, dont les résultats étaient jusqu'à présent limités, connait un regain d'intérêt du fait de l'apport de nouvelles technologies en endoscopie bronchique.

[Techniques and strategy of pathological sampling in the diagnostic and therapeutic management of lung cancer]. / Techniques et stratégie de prise en charge des prélèvements anatomopathologiques dans le cadre de l'approche diagnostique et thérapeutique du cancer bronchique.

Histopathology is key to the diagnosis and staging of lung cancer. This analysis requires tissue sampling from primary and/or metastatic lesions. The choice of sampling technique is intended to optimize diagnostic yield while avoiding unnecessarily invasive procedures. Recent developments in targeted therapy require increasingly precise histological and molecular characterization of the tumor. Therefore, pathologists must be economical with tissue samples to ensure that they have the opportunity to perform all the analyses required. More than ever, good communication between clinician, endoscopist or surgeon, and pathologist is essential. This is necessary to ensure that all participants in the process of lung cancer diagnosis collaborate to ensure that the appropriate number and type of biopsies are performed with the appropriate tissue sampling treatment. This will allow performance of all the necessary analyses leading to a more precise characterization of the tumor, and thus the optimal treatment for patients with lung cancer.

Drug interactions between voriconazole, darunavir/ritonavir and tenofovir/emtricitabine in an HIV-infected patient treated for Aspergillus candidus lung abscess.

We report an unusual case of pulmonary aspergillosis in a patient with AIDS and we demonstrated the drug-drug interactions between voriconazole, darunavir/ritonavir and tenofovir/emtricitabine. The combination darunavir-ritonavir-voriconazole should be avoided.

Evaluating the tolerance of young hybrid poplar trees to recycled waters high in salinity and boron.

The successful adoption of water recycling strategies in many arid regions will require crops able to tolerate poor-quality waters. We evaluated different clones for salt and boron (B) tolerance within each of seven genetically distinct genomic groups (e.g., deltoides, deltoides x nigra, trichocarpa x deltoides, trichocarpa x deltoides x maximowizcii, trichocarpa x deltoides x nigra, trichocarpa x nigra, trichocarpa x maximowizcii). During each evaluation period, different clones within each of the groups were irrigated with high sodium chloride (NaCl) salinity (i.e., 10-30 dS m(-1)) and B (i.e., 10 mg L(-1)) water up to a maximum of 150 days, for a 4-year testing period under micro-field plot conditions. Excessive accumulation (up to 6%) of chloride (Cl) likely caused toxicity symptoms (necrosis of the leaves) observed in the less tolerant clones, while leaf B concentrations rarely exceeded 300 mg kg(-1) DM in any clone. Increased soil salinity likely hindered the uptake of B by the clones. Our results show that a wide range of selected Populus clones, of parentage trichocarpa x nigra, followed by deltoides x nigra show potential salt and B tolerance as young trees to recycled waters high in salinity and B.

Critical role of cytosolic phospholipase A2{alpha} in bronchial mucus hypersecretion in CFTR-deficient mice.

Cystic fibrosis (CF) is due to mutations in the CF transmembrane conductance regulator gene CFTR. CF is characterised by mucus dehydration, chronic bacterial infection and inflammation, and increased levels of cytosolic phospholipase A2α (cPLA2α) products in airways. We aimed to examine the role of cPLA2α in the modulation of mucus production and inflammation in CFTR-deficient mice and epithelial cells. Mucus production was assessed using histological analyses, immuno-histochemistry and MUC5AC ELISA. cPLA2α activation was measured using an enzymatic assay and lung inflammation determined by histological analyses and polymorphonuclear neutrophil counts in bronchoalveolar lavages. In lungs from Cftr(-/-) mice, lipopolysaccharide induced mucus overproduction and MUC5AC expression associated with an increased cPLA2α activity. Mucus overproduction was mimicked by instillation of the cPLA2α product arachidonic acid, and abolished by either a cPLA2α null mutation or pharmacological inhibition. An increased cPLA2α activity was observed in bronchial explants from CF patients. CFTR silencing induced cPLA2α activation and MUC5AC expression in bronchial human epithelial cells. This expression was enhanced by arachidonic acid and reduced by cPLA2α inhibition. However, inhibition of CFTR chloride transport function had no effect on MUC5AC expression. Reduction of CFTR expression increased cPLA2α activity. This led to an enhanced mucus production in airway epithelia independent of CFTR chloride transport function. cPLA2α represents a suitable new target for therapeutic intervention in CF.

The value of endoscopic ultrasound after bronchoscopy to diagnose thoracic sarcoidosis.

A clinicoradiological presentation of thoracic sarcoidosis requires histopathology in order to establish the diagnosis. Flexible bronchoscopy has a reasonable diagnostic yield and is the procedure of first choice for diagnosis. Endoscopic ultrasound (endoscopic ultrasound-guided fine needle aspiration/endobronchial ultrasound-guided transbronchial needle aspiration) can help in the diagnosis of sarcoidosis. An implementation strategy of endoscopic ultrasound for the diagnosis of sarcoidosis following negative flexible bronchoscopy results was examined prospectively in 15 clinics. A total of 137 patients (92 males; median age 43 yrs) were included, and sarcoidosis was found in 115 (84%). Alternative diagnoses were tuberculosis, lymphangitis carcinomatosa, pneumoconiosis and alveolitis. All patients were sent for flexible bronchoscopy, which was performed in 121 (88%), resulting in a definite diagnosis in 57 (42%). A total of 80 patients were sent for endoscopic ultrasound, which could be performed in 72 (90%), yielding a definite diagnosis in 47 (59%). Endoscopic ultrasound following negative flexible bronchoscopy avoided a surgical procedure in 47 out of 80 patients. The sensitivity of flexible bronchoscopy for sarcoidosis was 45% (95% confidence interval 35-54%), but 62% (50-72%) if biopsy specimens were taken. The sensitivity of endoscopic ultrasound following negative flexible bronchoscopy results was 71% (58-82%). With this strategy, 97 out of 115 (84% (76-90%)) of proven sarcoidosis was diagnosed using endoscopy. This large prospective implementation study (trial number NCT00888212; ClinicalTrials.gov) shows that endoscopic ultrasound is valuable for diagnosing sarcoidosis after negative flexible bronchoscopy results.

Lamb wave propagation in a plate with a grooved surface with several spatial periodicities.

In order to investigate non-destructively the bonding between rough plates, the problem of Lamb waves propagating on a rough plate is addressed in this paper. Numerical analysis is performed on periodical gratings made of identical triangular grooves. If the surface profile is made up of grooves with one periodicity, then a mode conversion is observed. In the wave-number/frequency space, a phonon relation is written between phonons related to the grating and to the incident and reflected-converted modes. If the grooved surface is made up of several spatial periodicities, then the phonon relation is still verified. Signal processing allows us to give an interpretation of the results in the dual space (wave-number/frequency). An experimental study is also performed to corroborate the numerical predictions.

[Manual abdominal compression for the detection of expiratory flow limitation]. / La compression abdominale manuelle dans la détection de la limitation du débit expiratoire.

INTRODUCTION: Expiratory flow limitation (EFL) is a characteristic feature of chronic obstructive pulmonary disease (COPD) and leads to dynamic hyperinflation (DH) which is a major source of dyspnoea, particularly during exercise. STATE OF THE ART: A new technique for the detection of EFL, based on manual compression of the abdomen (MCA), was assessed both in normal subjects and patients with COPD. MCA was always associated with a moderate increase in pleural pressure and allowed the detection of EFL in a reproducible manner, in both the seated and supine postures. The technique was well tolerated. It was also a reliable method for the detection of EFL during exercise since EFL detection was effectively associated with the development of DH. Finally, MCA was also compared to NEP in patients with obstructive sleep apnoea syndrome (OSAS) and in these patients, MCA invariably increased expiratory flow whereas the NEP method produced flow limitation in some cases because of upper airway collapse. PERSPECTIVES: EFL detection with MCA may be clinically useful since EFL is a determinant of dyspnoea, affects ventilatory response to exercise as well as maximum exercise capacity. CONCLUSIONS: MCA is a reliable technique for the detection of EFL in different positions, during resting breathing or exercise, requiring neither special equipment nor patient cooperation.

Two distinct pathways for thymidylate (dTMP) synthesis in (hyper)thermophilic Bacteria and Archaea.

The hyperthermophilic anaerobic archaeon Pyrococcus abyssi, which lacks thymidine kinase, incorporates label from extracellular uracil, but not from thymidine, into its DNA. This implies that P. abyssi must synthesize dTMP (thymidylate), an essential precursor for DNA synthesis, de novo. However, iterative similarity searches of the three completed Pyrococcus genomes fail to detect candidate genes for canonical thymidylate synthase ThyA, suggesting the presence of alternative pathways for dTMP synthesis. Indeed, by identifying a novel class of flavin-dependent thymidylate synthases, ThyX, we have recently proven that two distinct pathways for de novo synthesis of dTMP are operational in the microbial world. While both thyX and thyA can be found in hyperthermophilic micro-organisms, the phylogenetic distribution of thyX among hyperthermophiles is wider than that of thyA. In this contribution, we discuss the differences in the distinct mechanisms of dTMP synthesis, with a special emphasis on hyperthermophilic micro-organisms.

Expiratory flow limitation during exercise in COPD: detection by manual compression of the abdominal wall.

Manual compression of the abdomen (MCA) during spontaneous expiration is a simple method for the detection of flow limitation in the chronic obstructive pulmonary disease (COPD) patients during resting breathing, based on comparison of flow/volume curves obtained during MCA with that of the preceding control breath. It was assessed whether this nonstandardized technique is also feasible during exercise. MCA was performed during resting breathing and constant-exercise work at one- and two-thirds maximal mechanical power output (W'max) in six normal subjects and 12 COPD patients. Changes in end-expiratory lung volume (EELV) were also studied. With the aid of inspection, abdominal palpation and lung auscultation, MCA could always be applied during expiration. Flow limitation was never detected in the six normal subjects, whereas four of the COPD patients were flow limited at rest, seven during exercise at one-third W'max and nine during exercise at two-thirds W'max. Expiratory flow limitation detected by MCA was always associated with an increase in EELV during exercise, indicating dynamic hyperinflation occurrence or increase. It is concluded that manual compression of the abdomen is a very simple and reliable method for the detection of flow limitation during exercise.

Effect of chest wall vibration on the canine diaphragm during breathing.

High-frequency mechanical vibration of the ribcage reduces dyspnoea in patients with chronic obstructive pulmonary disease, and the suggestion has been made that this effect might be related to a decrease in central respiratory drive resulting from an increase in afferent inputs from intercostal muscles. In the present studies, the effects of ribcage vibration on central respiratory drive have been assessed without the confounding influence of conscious reactions. The electromyographic (EMG) activity of the diaphragm and the changes in pleural (Ppl) and abdominal (Pab) pressure were measured in six anaesthetized, spontaneously-breathing dogs while the rostral, the middle, or the caudal portion of the ribcage was vibrated at intervals during inspiration. The EMG activity of the external and parasternal intercostals was also measured. Ribcage vibration consistently elicited a marked increase in the inspiratory EMG activity recorded from the external intercostals, thus indicating that the procedure did activate intercostal muscle spindles. However, no alteration in diaphragmatic or parasternal intercostal EMG activity was seen in any animal. Transdiaphragmatic pressure and the relationship between deltaPab and deltaPpl during inspiration were also unaltered. The authors conclude that ribcage vibration and, with it, stimulation of external intercostal muscle spindles has no significant influence on phrenic motoneurones or on medullary inspiratory neurones. It is unlikely, therefore, that the beneficial effect of the procedure on dyspnoea results from a specific reduction in central respiratory drive.

The 1-127 HA2 construct of influenza virus hemagglutinin induces cell-cell hemifusion.

Conformational changes in the HA2 subunit of influenza hemagglutinin (HA) are coupled to membrane fusion. We investigated the fusogenic activity of the polypeptide FHA2 representing 127 amino-terminal residues of the ectodomain of HA2. While the conformation of FHA2 both at neutral and at low pH is nearly identical to the final low-pH conformation of HA2, FHA2 still induces lipid mixing between liposomes in a low-pH-dependent manner. Here, we found that FHA2 induces lipid mixing between bound cells, indicating that the "spring-loaded" energy is not required for FHA2-mediated membrane merger. Although, unlike HA, FHA2 did not form an expanding fusion pore, both acidic pH and membrane concentrations of FHA2, required for lipid mixing, have been close to those required for HA-mediated fusion. Similar to what is observed for HA, FHA2-induced lipid mixing was reversibly blocked by lysophosphatidylcholine and low temperature, 4 degrees C. The same genetic modification of the fusion peptide inhibits both HA- and FHA2-fusogenic activities. The kink region of FHA2, critical for FHA2-mediated lipid mixing, was exposed in the low-pH conformation of the whole HA prior to fusion. The ability of FHA2 to mediate lipid mixing very similar to HA-mediated lipid mixing is consistent with the hypothesis that hemifusion requires just a portion of the energy released in the conformational change of HA at acidic pH.

Self-assembly of influenza hemagglutinin: studies of ectodomain aggregation by in situ atomic force microscopy.

We have used in situ tapping mode atomic force microscopy (AFM) to study the structural morphology of two fragments of the influenza hemagglutinin protein bound to supported bilayers. The two proteins that we studied are the bromelain-cleaved hemagglutinin (BHA), corresponding to the full ectodomain of the hemagglutinin protein, and FHA2, the 127 amino acid N-terminal fragment of the HA2 subunit of the hemagglutinin protein. While BHA is water soluble at neutral pH and is known to bind to membranes via specific interactions with a viral receptor, FHA2 can only be solubilized in water with an appropriate detergent. Furthermore, FHA2 is known to readily bind to membranes at neutral pH in the absence of a receptor. Our in situ AFM studies demonstrated that, when bound to supported bilayers at neutral pH, both these proteins are self-assembled as single trimeric molecules. In situ acidification resulted in further lateral association of the FHA2 without a large perturbation of the bilayer. In contrast, BHA remained largely unaffected by acidification, except in areas of exposed mica where it is aggregated. Remarkably, these results are consistent with previous observations that FHA2 promotes membrane fusion while BHA only induces liposome leakage at low pH. The results presented here are the first example of in situ imaging of the ectodomain of a viral envelope protein allowing characterization of the real-time self-assembly of a membrane fusion protein.

Detection of expiratory flow limitation by manual compression of the abdominal wall.

We have assessed a new method, manual compression of the abdominal wall (MCA) during expiration, in the detection of expiratory flow limitation. Twelve stable patients with chronic obstructive pulmonary disease (COPD) and five normal subjects were studied during spontaneous breathing in the supine and seated posture. MCA was performed during expiration with one hand at the umbilical level and we measured flow, volume, pleural (Ppl) and gastric (Pga) pressures and abdominal anteroposterior (AP) diameter at the umbilical level with magnetometers. No increase in expiratory flow during MCA relative to the preceding breath despite associated increases in pressures was considered as indicating expiratory flow limitation. In seven additional patients with increased upper airway collapsibility (obstructive sleep apnea syndrome [OSAS]), MCA was compared with negative expiratory pressure (NEP). In normal seated subjects, MCA was associated with a decrease in abdominal AP dimension (mean +/- SD: -27 +/- 6%), an increase in Pga (14.7 +/- 7.4 cm H(2)O) and Ppl (6.2 +/- 2.2 cm H(2)O), and an increase in expiratory flow. MCA caused similar changes in abdominal AP dimension and pressures in seated patients with COPD but six of them (50%), including four patients with FEV(1) less than 1 L, had no increase in expiratory flow. In the supine posture, MCA always increased expiratory flow in normal subjects but four additional patients with COPD showed evidence of flow limitation. MCA invariably increased expiratory flow in patients with OSAS whereas the NEP method suggested flow limitation in some cases. We conclude that MCA is a very simple method that allows detection of flow limitation in different positions.

Fine-needle aspiration biopsy of a glomus tumor of the stomach.

A glomus tumor of the stomach was found as an incidental finding on routine ultrasound in a 72-yr-old asymptomatic woman. A fine-needle aspiration biopsy (FNAB) was performed and was initially interpreted as a well-differentiated neuroendocrine neoplasm, possibly a carcinoid tumor. The aspirate revealed tightly packed nests or clusters of uniform, small, round to polygonal cells with scanty, faintly eosinophilic or clear cytoplasm and ill-defined cell borders. The nuclei were uniform, and round to oval, and contained a granular chromatin pattern and inconspicuous nucleoli. Very occasional intranuclear cytoplasmic inclusions were seen. Laparotomy and a wedge resection of the stomach were performed. The surgical pathology findings revealed a glomus tumor which was confirmed by immunohistochemical stains and ultrastructural studies. Since glomus tumors of the stomach are essentially benign and are amenable to conservative excision, it is important to separate them, preoperatively, from more aggressive gastric neoplasms. FNAB offers a rapid, cost-effective method of diagnosing this entity. We present the cytological, histological, ultrastructural, and immunocytochemical features of this particular gastric neoplasm, along with differential diagnoses.