Automatic selection of tidal volume, respiratory frequency and minute ventilation in intubated ICU patients as start up procedure for closed-loop controlled ventilation.

OBJECTIVE: Before a patient can be connected to a mechanical ventilator, the controls of the apparatus need to be set up appropriately. Today, this is done by the intensive care professional. With the advent of closed loop controlled mechanical ventilation, methods will be needed to select appropriate start up settings automatically. The objective of our study was to test such a computerized method which could eventually be used as a start-up procedure (first 5-10 minutes of ventilation) for closed-loop controlled ventilation. DESIGN: Prospective Study. SETTINGS: ICU's in two adult and one children's hospital. PATIENTS: 25 critically ill adult patients (age > or = 15 y) and 17 critically ill children selected at random were studied. INTERVENTIONS: To stimulate 'initial connection', the patients were disconnected from their ventilator and transiently connected to a modified Hamilton AMADEUS ventilator for maximally one minute. During that time they were ventilated with a fixed and standardized breath pattern (Test Breaths) based on pressure controlled synchronized intermittent mandatory ventilation (PCSIMV). MEASUREMENTS AND MAIN RESULTS: Measurements of airway flow, airway pressure and instantaneous CO2 concentration using a mainstream CO2 analyzer were made at the mouth during application of the Test-Breaths. Test-Breaths were analyzed in terms of tidal volume, expiratory time constant and series dead space. Using this data an initial ventilation pattern consisting of respiratory frequency and tidal volume was calculated. This ventilation pattern was compared to the one measured prior to the onset of the study using a two-tailed paired t-test. Additionally, it was compared to a conventional method for setting up ventilators. The computer-proposed ventilation pattern did not differ significantly from the actual pattern (p > 0.05), while the conventional method did. However the scatter was large and in 6 cases deviations in the minute ventilation of more than 50% were observed. CONCLUSIONS: The analysis of standardized Test Breaths allows automatic determination of an initial ventilation pattern for intubated ICU patients. While this pattern does not seem to be superior to the one chosen by the conventional method, it is derived fully automatically and without need for manual patient data entry such as weight or height. This makes the method potentially useful as a start up procedure for closed-loop controlled ventilation.

Objective Sleep Structure and Cardiovascular Risk Factors in the General Population: The HypnoLaus Study.

STUDY OBJECTIVES: To evaluate the association between objective sleep measures and metabolic syndrome (MS), hypertension, diabetes, and obesity. DESIGN: Cross-sectional study. SETTING: General population sample. PARTICIPANTS: There were 2,162 patients (51.2% women, mean age 58.4 ± 11.1). INTERVENTIONS: Patients were evaluated for hypertension, diabetes, overweight/obesity, and MS, and underwent a full polysomnography (PSG). MEASUREMENTS AND RESULTS: PSG measured variables included: total sleep time (TST), percentage and time spent in slow wave sleep (SWS) and in rapid eye movement (REM) sleep, sleep efficiency and arousal index (ArI). In univariate analyses, MS was associated with decreased TST, SWS, REM sleep, and sleep efficiency, and increased ArI. After adjustment for age, sex, smoking, alcohol, physical activity, drugs that affect sleep and depression, the ArI remained significantly higher, but the difference disappeared in patients without significant sleep disordered breathing (SDB). Differences in sleep structure were also found according to the presence or absence of hypertension, diabetes, and overweight/obesity in univariate analysis. However, these differences were attenuated after multivariate adjustment and after excluding subjects with significant SDB. CONCLUSIONS: In this population-based sample we found significant associations between sleep structure and MS, hypertension, diabetes, and obesity. However, these associations were cancelled after multivariate adjustment. We conclude that normal variations in sleep contribute little if any to MS and associated disorders.

Immunoelectron microscopic localization of transforming growth factor alpha in rat colon

Transforming growth factor alpha (TGF alpha) is a polypeptide, which binds to the epidermal growth factor receptor to carry out its function related to cell proliferation and differentiation. The ultrastructural localisation of TGF alpha was studied in both the proximal and the distal colon. The columnar cells, lining the surface epithelium of the proximal colon, showed a strong immunoreactivity in the polyribosomes and in the interdigitations of the lateral membrane. The columnar cells of the crypts and the goblet cells in both the proximal and the distal colon showed the immunostaining in the cis and trans cisternae of the Golgi apparatus. TGF alpha seems to be processed differently in the surface columnar cells and in the crypt columnar cells and goblet cells. Moreover, it probably has different roles in proliferation and differentiation.

Cholesterol transport from late endosomes to the Golgi regulates t-SNARE trafficking, assembly, and function

Cholesterol regulates plasma membrane (PM) association and functioning of syntaxin-4 and soluble N-ethylmaleimide-sensitive fusion protein 23 (SNAP23) in the secretory pathway. However, the molecular mechanism and cellular cholesterol pools that determine the localization and assembly of these target membrane SNAP receptors (t-SNAREs) are largely unknown. We recently demonstrated that high levels of annexin A6 (AnxA6) induce accumulation of cholesterol in late endosomes, thereby reducing cholesterol in the Golgi and PM. This leads to an impaired supply of cholesterol needed for cytosolic phospholipase A2 (cPLA2) to drive Golgi vesiculation and caveolin transport to the cell surface. Using AnxA6-overexpressing cells as a model for cellular cholesterol imbalance, we identify impaired cholesterol egress from late endosomes and diminution of Golgi cholesterol as correlating with the sequestration of SNAP23/syntaxin-4 in Golgi membranes. Pharmacological accumulation of late endosomal cholesterol and cPLA2 inhibition induces a similar phenotype in control cells with low AnxA6 levels. Ectopic expression of Niemann-Pick C1 (NPC1) or exogenous cholesterol restores the location of SNAP23 and syntaxin-4 within the PM. Importantly, AnxA6-mediated mislocalization of these t-SNAREs correlates with reduced secretion of cargo via the SNAP23/syntaxin-4¿dependent constitutive exocytic pathway. We thus conclude that inhibition of late endosomal export and Golgi cholesterol depletion modulate t-SNARE localization and functioning along the exocytic pathway.

Nonequilibrium patterns and shape fluctuations in reactive membranes

A simple kinetic model of a two-component deformable and reactive bilayer is presented. The two differently shaped components are interconverted by a nonequilibrium reaction, and a phenomenological coupling between local composition and curvature is proposed. When the two components are not miscible, linear stability analysis predicts, and numerical simulations show, the formation of stationary nonequilibrium composition/curvature patterns whose typical size is determined by the reactive process. For miscible components, a linearization of the dynamic equations is performed in order to evaluate the correlation function for shape fluctuations from which the behavior of these systems in micropipet aspiration experiments can be predicted.

Dynamics of a paramagnetic colloidal particle driven on a magnetic-bubble lattice

We present a theoretical study of the recently observed dynamical regimes of paramagnetic colloidal particles externally driven above a regular lattice of magnetic bubbles [P. Tierno, T. H. Johansen, and T. M. Fischer, Phys. Rev. Lett. 99, 038303 (2007)]. An external precessing magnetic field alters the potential generated by the surface of the film in such a way to either drive the particle circularly around one bubble, ballistically through the array, or in triangular orbits on the interstitial regions between the bubbles. In the ballistic regime, we observe different trajectories performed by the particles phase locked with the external driving. Superdiffusive motion, which was experimentally found bridging the localized and delocalized dynamics, emerge only by introducing a certain degree of randomness into the bubbles size distribution.

Generation of dynamic structures in nonequilibrium reactive membranes

We present a nonequlibrium approach for the study of a flexible bilayer whose two components induce distinct curvatures. In turn, the two components are interconverted by an externally promoted reaction. Phase separation of the two species in the surface results in the growth of domains characterized by different local composition and curvature modulations. This domain growth is limited by the effective mixing due to the interconversion reaction, leading to a finite characteristic domain size. In addition to these effects, first introduced in our earlier work [ Phys. Rev. E 71 051906 (2005)], the important new feature is the assumption that the reactive process actively affects the local curvature of the bilayer. Specifically, we suggest that a force energetically activated by external sources causes a modification of the shape of the membrane at the reaction site. Our results show the appearance of a rich and robust dynamical phenomenology that includes the generation of traveling and/or oscillatory patterns. Linear stability analysis, amplitude equations, and numerical simulations of the model kinetic equations confirm the occurrence of these spatiotemporal behaviors in nonequilibrium reactive bilayers.

Performance anxiety : cardiorespiratory activity in high- and low-anxious professional music students in a performance situation

Questionnaire studies indicate that high-anxious musicians may suffer from hyperventilation symptoms before and/or during performance. Reported symptoms include amongst others shortness of breath, fast or deep breathing, dizziness and thumping heart. A self-report study by Widmer, Conway, Cohen and Davies (1997) shows that up to seventy percent of the tested highly anxious musicians are hyperventilators during performance. However, no study has yet tested if these self-reported symptoms reflect actual cardiorespiratory changes just before and during performance. Disturbances in breathing patterns and hyperventilation may negatively affect the performance quality in stressful performance situations. The main goal of this study is to determine if music performance anxiety is manifest physiologically in specific correlates of cardiorespiratory activity. We studied 74 professional music students of Swiss Music Universities divided into two groups (high- and lowanxious) based on their self-reported performance anxiety (State-Trait Anxiety Inventory by Spielberger). The students were tested in three distinct situations: baseline, performance without audience, performance with audience. We measured a) breathing patterns, end-tidal carbon dioxide, which is a good non-invasive estimator for hyperventilation, and cardiac activation and b) self-perceived emotions and self-perceived physiological activation. Analyses of heart rate, respiratory rate, self-perceived palpitations, self-perceived shortness of breath and self-perceived anxiety for the 15 most and the 15 least anxious musicians show that high-anxious and low-anxious music students have a comparable physiological activation during the different measurement periods. However, highanxious music students feel significantly more anxious and perceive significantly stronger palpitations and significantly stronger shortness of breath just before and during a public performance. The results indicate that low- and high-anxious music students a) do not differ in the considered physiological responses and b) differ in the considered self-perceived physiological symptoms and the selfreported anxiety before and/or during a public performance.

Coronary magnetic resonance angiography in adolescents and young adults with kawasaki disease.

BACKGROUND: In patients with Kawasaki disease, serial evaluation of the distribution and size of coronary artery aneurysms (CAA) is necessary for risk stratification and therapeutic management. Although transthoracic echocardiography is often sufficient for this purpose initially, visualization of the coronary arteries becomes progressively more difficult as children grow. We sought to prospectively compare coronary magnetic resonance angiography (MRA) and x-ray coronary angiography findings in patients with CAA caused by Kawasaki disease. METHODS AND RESULTS: Six subjects (age 10 to 25 years) with known CAA from Kawasaki disease underwent coronary MRA using a free-breathing T2-prepared 3D bright blood segmented k-space gradient echo sequence with navigator gating and tracking. All patients underwent x-ray coronary angiography within a median of 75 days (range, 1 to 359 days) of coronary MRA. There was complete agreement between MRA and x-ray angiography in the detection of CAA (n=11), coronary artery stenoses (n=2), and coronary occlusions (n=2). Excellent agreement was found between the 2 techniques for detection of CAA maximal diameter (mean difference=0.4 +/- 0.6 mm) and length (mean difference=1.4 +/- 1.6 mm). The 2 methods showed very similar results for proximal coronary artery diameter (mean difference=0.2 +/- 0.5 mm) and CAA distance from the ostia (mean difference=0.1 +/- 1.5 mm). CONCLUSION: Free-breathing 3D coronary MRA accurately defines CAA in patients with Kawasaki disease. This technique may provide a non-invasive alternative when transthoracic echocardiography image quality is insufficient, thereby reducing the need for serial x-ray coronary angiography in this patient group.

Placental immaturity, endocardial fibroelastosis and fetal hypoxia.

We describe a term newborn who, after a normal gestational course, presented at birth with absent cardiac activity and no spontaneous breathing. Death occurred within 30 h. Autopsy revealed placental villous immaturity, multiple acute hypoxic lesions, but also chronic hypoxic lesions like endocardial fibroelastosis. This striking association of endocardial fibroelastosis and placental villous immaturity is reviewed and correlated with 2 other cases of placental villous immaturity that led to in utero death at 39 and 41 weeks of gestation. Placental villous immaturity must be suspected and looked for by both pediatricians and obstetricians in every case of stillbirth or perinatal asphyxia of unclear origin. In order to minimize the risk of recurrence in further pregnancies, elective cesarean section may be considered.

Transcriptional control of the Notch1 tumour suppressor gene

Abstract : The Notch pathway is an important regulator of differentiation and carcinogenesis. In keratinocytes and possibly other specific epithelial cell types, it acts as tumour suppressor. Expression of endogenous Notch1 gene is markedly reduced in keratinocyte-derived squamous cell carcinoma (SCC) and cervical cancer cells, as well as in prostate cancer cell lines, and this difference is, at least in part, at the transcriptional level. Little is known on transcriptional control of the Notch1 gene with the exception that it is a p53-target. Our work focused on the mechanisms involved in the different transcription level of the Notch1 gene in normal versus cancer cells. We show that the fully active minimal Notch1 promoter is differentially controlled in normal versus cancer cells. It consists of two distinct regions, one downstream of the transcription start site, which is likely to bind the basic transcription apparatus, and one upstream region characterized by highly GC-rich sequence. This latter region binds Sp/KLF family members, specifically Spa and KLF4, which is upregulated in cancer cells. This is functionally significant as KLF4 overexpression is sufficient to downmodulate Notchl gene transcription, while KLF4 knockdown, in combination with Spa, results in Notch1 upregulation. Control of Notch1 by KLF4/Sp3 is independent of p53. Biochemically, KLF4/Sp3 seem to affect preferentially the initiation step of Notch1 gene transcription, while p53 controls both initiation and elongation steps. Thus, the Notch1 gene is a negative Sp3/KLF4-target and this mechanism contributes, in parallel with p53, to Notch1 downregulation in cancer. Résumé : La voie de signalisation induite par Notch est considérablement impliquée dans la différenciation des cellules et dans la carcinogénèse. Dans les kératinocytes ainsi que dans d'autres types cellulaires de l'épithelium, il agit comme suppresseur de tumeur. L'expression endogène de Notch1 est remarquablement réduite dans les cellules du carcinome spino-cellulaire et du cancer du col de l'utérus ou dans les lignées cellulaires du cancer de la prostate. Cette différence s'explique, du moins en partie, par le niveau de transcription. Peu de choses sont connues sur le contrôle transcriptionnel de Notch1 à l'exception du fait qu'il soit une cible de p53. Notre travail s'est concentré sur les mécanismes impliqués dans la transcription de Notch1, mécanismes qui diffèrent entre les cellules normales et les cellules cancéreuses. Nous avons trouvé la plus petite région du promoteur de Notch1 qui est suffisante pour induire un haut niveau transcriptionnel et qui est contrôlée différemment dans les cellules normales et les cellules cancéreuses. Elle est constituée de deux régions distinctes: une en aval du site de départ de la transcription, qui lie probablement le complexe de base pour la transcription, et une en amont caractérisée par une séquence riche en GC. Cette région lie les membres de la famille Sp/KLF, spécifiquement Sp3 et KLF4, qui sont surexprimés dans les cellules cancéreuses. Ceci est fonctionnellement significatif car la surexpression de KLF4 dans les kératinocytes est suffisante pour diminuer la transcription de Notch1, alors que l'inhibition de KLF4 et de Spa, résulte en une augmentation de Notch1. En outre, le contrôle de Notch1 par KLF4 et Spa est indépendant de p53. Biochimiquement, KLF4 et Spa semblent plutôt affecter l'initiation de la transcription de Notch1 alors que p53 contrôle aussi bien l'initiation que l'élongation. En conclusion, le gène Notch1 est inhibé par Spa et KLF4: ce mécanisme contribue, en parallèle à p53, à diminuer l'expression de Notch1 dans les cellules cancéreuses.

Alternativas del moldeado en alteraciones del antepié

El molde en carga controlada sobre espumas de poliuretano es la técnica de moldeado que mejores resultados nos está ofreciendo en la actualidad, ya que permite la obtención del molde en posición más fisiológica, con el paciente en bipedestación en ángulo y base de marcha, permitiendo la distensión de tejidos blandos evitando riesgo de hipercorrecciones, además de poder realizarlo sobre un banco de marcha informatizado permitiendo visualizar a través del monitor la huella plantar simultáneamente a la confección de dicho molde. La importancia de la realización de tratamientos ortopodológicos individualizados o personalizados en función de cada patología, nos ha conducido a realizar también el molde de forma personalizada en función del diagnóstico obtenido. Para ello hemos descrito una técnica modificada del molde en carga controlada aplicando el sistema diagnóstico "Functional block test" en su confección. El sistema diagnóstico "block test", descrito por el Doctor Whitney de la Temple University de Philadelphia, es de gran utilidad en laexploración clínica diaria. Se basa en el diseño de diferentes cuñas o elementos compensadores de cada patología existente en el pie en cada uno de los tres planos corporales. La aplicación del elemento correspondiente a la patología situado bajo el pie con el paciente en blpedestación conduce a la articulación subastragalina hacia su neutralidad y por tanto ayuda a confirmar el diagnóstico obtenido. La aplicación de dichos elementos en la confección del molde en carga permite un mejor control de la posición neutra del pie y un óptimo reflejo de dicha patología en el molde confeccionado, permitiendo posteriormente su correcta compensación en el tratamiento ortopodológico..

Efecto de las ortesis plantares en los cambios de presión del antepié

El uso de soportes plantares ante la presenda de sobrecargas metatarsales se ha mostrado como un tratamiento muy efectivo ante la sintomatología dolorosa asociada a esta problemática del antepié, secundariaprincipalmente a problemas biomecánicos. Este estudio trata de demostrar la justificación del efecto de estos tratamientos, mediante el análisis de los cambios de presión que suceden en el antepié con el uso de un soporte plantar prefabricado y otro confeccionado a medida. Los resultados ofrecen cambios significativos con el uso de los tratamientos ortopodológicos, principalmente con los individualizados, es decir, los confeccionados a medida sobre un molde del pie.

Melanic color-dependent anti-predator behavior strategies in barn owl nestlings

The arms race between predators and prey has led to morphological and behavioral adaptations. Different antipredator strategies can coexist within a population if each strategy is the result of a trade-off with competing demands. Antipredator behavior can be associated with morphological traits, like color patterns, either because in the context of sexual selection, coloration signals the ability to avoid predators or because coloration is a naturally selected trait useful in avoiding predators. Because in the barn owl (Tyto alba), heritable eumelanic plumage coloration is associated with the glucocorticoid-dependent response to stress, we tested whether antipredator behavior is also related to this trait. Compared with small-spotted nestlings, individuals displaying larger black spots hissed more intensely in the presence of humans, feigned death longer, had a lower breathing rate under stress, and were more docile when handled. Cross-fostering experiments showed that the covariation between the spot size and the duration of feigning death was inherited from the biological mother, whereas covariation between spot size and docility was inherited from the biological father. Our results confirm that melanin-based coloration is associated with suites of behavioral traits, which are under both genetic and environmental influence. Coloration can thus evolve as a direct or indirect response to predation, but it can also be a signal of antipredator strategies to potential mates.