Ventilation area measured with eit in order to optimize peep settings in mechanically ventilated patients

INTRODUCTION. Electrical Impedance Tomography (EIT) is a non-invasive imaging technique, which can be used to visualize ventilation. Ventilation will be measured by impedance changes due to ventilation. OBJECTIVES. The aim of this study was to optimize PEEP settings based on the ventilation area of EIT images during a decremental PEEP trial. METHODS. After a recruitment maneuver, a decremental PEEP trial was performed in 10 mechanically ventilated post cardiac surgery patients. Ventilation area, blood gases, FRC and compliance were measured at each PEEP level. The ventilation area was defined as the surface of ventilation at one lung slice measured with EIT and was expressed as percentage of its maximum obtained during a recruitment maneuver (RM). RESULTS. The amount of ventilated pixels during the RM is set as 100 %. Figure 1 shows the amount of ventilated pixels as percentage compared to its maximum during the RM. The ventilation area was significantly smaller at 5 and 0 PEEP compared to its maximum at both the dependent and non-dependent lung. Also PaO2/FiO2 and FRC were significantly lower at these PEEP levels. (Figure presented) Bars represent the mean + SD. Black = dependent lung region, White = non-dependent lung region. *

Hadroproduction of the Chi1 and Chi2 States of Charmonium in 800 GeV/c Proton-Silicon Interactions

The cross sections for the hadroproduction of the Chi1 and Chi2 states of charmonium in proton-silicon collisions at sqrt{s}=38.8 GeV have been measured in Fermilab fixed target Experiment 771. The Chi states were observed via their radiative decay to J/psi+gamma, where the photon converted to e+e- in the material of the spectrometer. The measured values for the Chi1 and Chi2 cross sections for x_F>0 are 263+-69(stat)+-32(syst) and 498+-143(stat)+-67(syst) nb per nucleon respectively. The resulting sigma(Chi1}/sigma(Chi2) ratio of 0.53+-0.20(stat)+-0.07(syst), although somewhat larger than most theoretical expectations, can be accomodated by the latest theoretical estimates.Comment: 4 pages, 4 figure

Zinc-Regulated DNA Binding of the Yeast Zap1 Zinc-Responsive Activator

The Zap1 transcription factor of Saccharomyces cerevisiae plays a central role in zinc homeostasis by controlling the expression of genes involved in zinc metabolism. Zap1 is active in zinc-limited cells and repressed in replete cells. At the transcriptional level, Zap1 controls its own expression via positive autoregulation. In addition, Zap1's two activation domains are regulated independently of each other by zinc binding directly to those regions and repressing activation function. In this report, we show that Zap1 DNA binding is also inhibited by zinc. DMS footprinting showed that Zap1 target gene promoter occupancy is regulated with or without transcriptional autoregulation. These results were confirmed using chromatin immunoprecipitation. Zinc regulation of DNA binding activity mapped to the DNA binding domain indicating other parts of Zap1 are unnecessary for this control. Overexpression of Zap1 overrode DNA binding regulation and resulted in constitutive promoter occupancy. Under these conditions of constitutive binding, both the zinc dose response of Zap1 activity and cellular zinc accumulation were altered suggesting the importance of DNA binding control to zinc homeostasis. Thus, our results indicated that zinc regulates Zap1 activity post-translationally via three independent mechanisms, all of which contribute to the overall zinc responsiveness of Zap1

A biophysical model of endocannabinoid-mediated short term depression in hippocampal inhibition

Memories are believed to be represented in the synaptic pathways of vastly interconnected networks of neurons. The plasticity of synapses, that is, their strengthening and weakening depending on neuronal activity, is believed to be the basis of learning and establishing memories. An increasing number of studies indicate that endocannabinoids have a widespread action on brain function through modulation of synap–tic transmission and plasticity. Recent experimental studies have characterised the role of endocannabinoids in mediating both short- and long-term synaptic plasticity in various brain regions including the hippocampus, a brain region strongly associated with cognitive functions, such as learning and memory. Here, we present a biophysically plausible model of cannabinoid retrograde signalling at the synaptic level and investigate how this signalling mediates depolarisation induced suppression of inhibition (DSI), a prominent form of shortterm synaptic depression in inhibitory transmission in hippocampus. The model successfully captures many of the key characteristics of DSI in the hippocampus, as observed experimentally, with a minimal yet sufficient mathematical description of the major signalling molecules and cascades involved. More specifically, this model serves as a framework to test hypotheses on the factors determining the variability of DSI and investigate under which conditions it can be evoked. The model reveals the frequency and duration bands in which the post-synaptic cell can be sufficiently stimulated to elicit DSI. Moreover, the model provides key insights on how the state of the inhibitory cell modulates DSI according to its firing rate and relative timing to the post-synaptic activation. Thus, it provides concrete suggestions to further investigate experimentally how DSI modulates and is modulated by neuronal activity in the brain. Importantly, this model serves as a stepping stone for future deciphering of the role of endocannabinoids in synaptic transmission as a feedback mechanism both at synaptic and network level

Purinergic signalling links mechanical breath profile and alveolar mechanics with the pro-inflammatory innate immune response causing ventilation-induced lung injury

Severe pulmonary infection or vigorous cyclic deformation of the alveolar epithelial type I (AT I) cells by mechanical ventilation leads to massive extracellular ATP release. High levels of extracellular ATP saturate the ATP hydrolysis enzymes CD39 and CD73 resulting in persistent high ATP levels despite the conversion to adenosine. Above a certain level, extracellular ATP molecules act as danger-associated molecular patterns (DAMPs) and activate the pro-inflammatory response of the innate immunity through purinergic receptors on the surface of the immune cells. This results in lung tissue inflammation, capillary leakage, interstitial and alveolar oedema and lung injury reducing the production of surfactant by the damaged AT II cells and deactivating the surfactant function by the concomitant extravasated serum proteins through capillary leakage followed by a substantial increase in alveolar surface tension and alveolar collapse. The resulting inhomogeneous ventilation of the lungs is an important mechanism in the development of ventilation-induced lung injury. The high levels of extracellular ATP and the upregulation of ecto-enzymes and soluble enzymes that hydrolyse ATP to adenosine (CD39 and CD73) increase the extracellular adenosine levels that inhibit the innate and adaptive immune responses rendering the host susceptible to infection by invading microorganisms. Moreover, high levels of extracellular adenosine increase the expression, the production and the activation of pro-fibrotic proteins (such as TGF-β, α-SMA, etc.) followed by the establishment of lung fibrosis

The association of ethnicity with electronically measured adherence to inhaled corticosteroids in children

Purpose To investigate the association of ethnicity with objectively, electronically measured adherence to inhaled corticosteroids (ICS) in a multicultural population of children with asthma in the city of Amsterdam. Methods The study was designed as a prospective, observational multicenter study in which adherence to ICS and potential risk factors for adherence to ICS were measured in a cohort of Moroccan and native Dutch children with asthma. Electronic adherence measurements were performed for 3 months per patient using a Real Time Medication Monitoring (RTMM) system. Ethnicity and other potential risk factors, such as socio-economic status, asthma control and parental medication beliefs, were extracted f Results A total of 90 children (aged 1-11 years) were included in the study and data of 87 children were used for analysis. Average adherence to ICS was 49.3 %. Native Dutch children showed higher adherence to ICS than Moroccan children (55.9 vs. 42.5 %, respectively; p=0.044, univariate analysis). After correction for confounders (>3 annual visits to the paediatric outpatient clinic, regular use of a spacer during inhalation), the final regression model showed that ethnicity was independently a Conclusions In our Western European population of inner city children with asthma, poor adherence to ICS was a serious problem, and even somewhat more so in ethnic minorities. Paediatricians involved in asthma treatment should be aware of these cultural differences in medication-taking behaviour, but further studies are needed to elucidate the causal mechanism

The association of ethnicity with electronically measured adherence to inhaled corticosteroids in children.

Background: Regular use of ICS can improve asthma control and reduce hospital admissions and mortality. Still, nonadherence is an important problem in asthma. Poor adherence seems to be a particular concern amongst ethnic minority patients and some evidence exits that ethnic disparities in asthma severity may be caused by poor adherence to ICS. Objectives: To investigate the impact of ethnicity on objectively, electronically measured adherence to inhaled corticosteroids (ICS) in a multicultural population of children with asthma in the city of Amsterdam. Methods: The study was designed as a prospective, observational multicenter study in which adherence to ICS and potential risk factors for adherence to ICS were measured in a cohort of Moroccan and native Dutch children with asthma. Electronic adherence measurements were performed for 3 months per patient using Real Time Medication Monitoring (RTMM). Ethnicity and other potential risk factors such as socio-economic status, asthma control, asthma severity and parental medication beliefs were extracted from medical records or parent interviews. The association between adherence and ethnicity was analyzed using multivariate linear regression analysis. Results: 94 children (aged 1–11 years) were included in the study and data of 87 children were used for analysis. On average, adherence to ICS was 49.3%. Native Dutch children showed higher adherence to ICS than Moroccans (55.9% vs. 42.5%, p=0.044, univariate analysis). Potential risk factors that were associated with adherence univariately (p0.2) were - next to ethnicity - subsequently entered into the multivariate model, resulting in a model including ‘>3 annual visits to the paediatric outpatient clinic’ and ‘regular use of a spacer during inhalation’. This model showed that ethnicity was independently associated with adherence (p=0.028). Conclusions: Poor adherence to ICS is a major concern, especially in ethnic minority children with asthma. Paediatricians involved in asthma treatment should be aware of the impact of ethnicity on adherence to ICS and could use this information to further enhance adherence and thus optimize asthma therapy in children. (aut. ref.