Percutaneous pulmonary valve implantation (PPVI) with a SAPIEN 3 valve is effective for treating treat right ventricle outflow (RVOT) dysfunction. A modified technique was developed without ...prestenting using a protective valve delivery method. We aimed to compare the procedural results of the modified technique group (MTG) to those of patients in a conventional technique group (CTG).
We designed a matched before-after study. All consecutive PPVI with SAPIEN 3 performed in the MTG over 9 months were matched, based on the RVOT type and size, to consecutive procedures performed previously with SAPIEN 3.
A total of 54 patients were included, equally distributed in the two groups. The sizes of the SAPIEN 3 valves were 23 mm (n = 9), 26 mm (n = 9), 29 mm (n = 36). The two groups were similar regarding demographic data, RVOT type, and pre-procedure hemodynamics. PPVI was performed in a single procedure in all patients of the MTG, whereas six (22.2%) patients of the CTG group underwent prestenting as a first step and valve implantation later (
= 0.02). The procedures were successful in all cases. Stent embolization was reported in two patients (7.4%) in the CTG, which were impacted in pulmonary arteries. In one case (3.7%), in the MTG, an unstable 29 mm SAPIEN 3 valve was stabilized with two stents and additional valve-in-valve implantation. The hemodynamics results were good in all cases, without significant differences between the two groups. The procedures' durations and fluoroscopy times were significantly reduced in the MTG (48.1 versus 82.6 min,
< 0.0001; 15.2 versus 29.8 min,
= 0.0002). During follow-up, neither stent fracture nor valve dysfunction was noticed in either group.
PPVI without prestenting and with a protective delivery method of the SAPIEN 3 valve significantly reduces the procedure's complexity, the duration, and the irradiation while maintaining excellent hemodynamics results in selected cases.
When modelling the Antarctic ice sheet, the velocity of the ice flow is linked to its temperature. Depending on the thermal rate, the flow rate may vary between deformation and sliding. In this ...study, we focus on the geothermal flux because it is the least well-known component of the heat equation, and because it constrains the temperature at the bottom of the ice sheet. We used available geological data to build a map of the geothermal flux, which was found to increase from 51 mW/m
2 in East Antarctica to 68 mW/m
2 in West Antarctica. These values were integrated in the computation of a basal temperature map. The available map of hydrological networks clearly shows more melted areas in West Antarctica than in the earlier results. So we suggest that the model should be forced with higher geothermal flux values, over 85 mW/m
2 in this sector. This increase is in good agreement with published results which found a geothermal flux three times higher in West Antarctica. Finally, we computed the bottom melt rate over the ice sheet area which has a mean value of 3.5 mm/yr resulting in a lost of melted ice equal to 1% of the total mass balance.
The mechanisms leading to enamel caries and lesions in hydroxyapatite (HAP) pellets systems are poorly understood. The kinetics of enamel and HAP demineralisation are usually controlled by surface ...reactions, but the surface layer retention suggests that diffusion in and out of the dissolving solid affects the kinetics of caries-like lesions formation. This project aimed at gaining some understanding of the physico-chemical processes occurring during caries lesion formation. Mineral loss was quantified l)'Sing X-ray scanning microradiography which provided precise and repeatable measurements. The use of a solid-state photon detector allowed photon energy discrimination, so that a near monochromatic beam could be used. In the first study, enamel and HAP samples were submitted alternately to a demineralising buffer and water with switching periods from 0.5 to 4 h. Mean rates of demineralisation decreased as the switching period increased, suggesting that demineralisation conditions within the solid persisted for a time after switching to water. A mathematical model was developed to fit the results. In the second study, HAP sections were separated from the demineralising buffer by an aqueous column 0 to 0.9 cm long. The rate of demineralisation decreased as the length increased, suggesting outward diffusion of dissolved HAP controlled the kinetics of demineralisation. Mathematical modelling based on Fick's diffusion supported this interpretation of the experimental results. The third study focused on the demineralising behaviour of points at increasing depths below the HAP surface. This showed that mineral redeposition occurred near the solid surface. In the last study, samples were submitted to demineralising buffers (same pH) with increasing ionic strength (increase of inert electrolytes concentration). The rate of demineralisation increased with the ionic strength while the surface layer formation was significantly suppressed. This suggests that coupled diffusion between inflow of acid and outflow ofdissolution products is important in surface layer formation.
The vascular remodeling responsible for pulmonary arterial hypertension (PAH) involves predominantly the accumulation of α-smooth muscle actin-expressing mesenchymal-like cells in obstructive ...pulmonary vascular lesions. Endothelial-to-mesenchymal transition (EndoMT) may be a source of those α-smooth muscle actin-expressing cells.
In situ evidence of EndoMT in human PAH was obtained by using confocal microscopy of multiple fluorescent stainings at the arterial level, and by using transmission electron microscopy and correlative light and electron microscopy at the ultrastructural level. Findings were confirmed by in vitro analyses of human PAH and control cultured pulmonary artery endothelial cells. In addition, the mRNA and protein signature of EndoMT was recognized at the arterial and lung level by quantitative real-time polymerase chain reaction and Western blot analyses. We confirmed our human observations in established animal models of pulmonary hypertension (monocrotaline and SuHx). After establishing the first genetically modified rat model linked to BMPR2 mutations (BMPR2(Δ140Ex1/+) rats), we demonstrated that EndoMT is linked to alterations in signaling of BMPR2, a gene that is mutated in 70% of cases of familial PAH and in 10% to 40% of cases of idiopathic PAH. We identified molecular actors of this pathological transition, including twist overexpression and vimentin phosphorylation. We demonstrated that rapamycin partially reversed the protein expression patterns of EndoMT, improved experimental PAH, and decreased the migration of human pulmonary artery endothelial cells, providing the proof of concept that EndoMT is druggable.
EndoMT is linked to alterations in BPMR2 signaling and is involved in the occlusive vas cular remodeling of PAH, findings that may have therapeutic implications.
A granular material is a complex system which exhibits non-trivial transitions between the static, the quasi-static and the dynamical states. Indeed, an assembly of grains can behave like a solid or ...a fluid according to the applied stress. In between solid and fluid granular states, very slow dynamics are observed. When a complete macroscopic characterization of a powder is needed, all these granular states have to be precisely analyzed. In this paper, we show how three measurement techniques can be used to measure the physical properties of a powder. The measurements are based on classical tests modified to meet the recent fundamental researches on granular materials. The static properties of the powder are analyzed through the shape of a heap. The quasi-static behavior is studied with the analysis of the compaction dynamics. Finally, the dynamical regime is monitored through the flow in a rotating drum. In order to illustrate how these measurements can be used in practical cases, analyses are performed with three types of granular materials: silicon carbide abrasives, flours and rice. These selected materials allow to show the influence of the different parameters (grain size, grain size distribution, grain shape) on the macroscopic properties of the assembly. Moreover, these studies show the pertinence of the parameters obtained with the proposed techniques for the rheological characterization of powders and grains.
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► Three measurement techniques are proposed for the characterization of powders. ► Static, quasistatic and dynamic properties of powders are considered. ► The techniques are based on classical tests modified to meet the recent requirements. ► Three typical granular materials allow to illustrate the measurement techniques. ► Improved repose angle, avalanche angle and tap density measurements are used.
Obsessive–compulsive disorder (OCD) is a severe mental illness. OCD symptoms are often resistant to available treatments. Abnormalities within the orbitofronto-striato-pallido-thalamic circuitry, ...especially orbitofrontal cortex (OFC) hyperactivity and cerebellar hypoactivity have been observed in patients. Non-invasive brain stimulation studies have indicated that transcranial direct current stimulation (tDCS) may be a useful alternative to alleviate treatment-resistant symptoms in various neuropsychiatric conditions.
In an open-label pilot study, 8 patients with treatment-resistant OCD received 10 sessions (twice a day) of 2mA tDCS applied with the cathode over the left OFC and the anode over the right cerebellum. OCD (Y-BOCS and OCD-VAS) as well as depressive (MADRS) symptoms were measured 4 times: one time before tDCS and 3 times after (immediately after, 1 and 3months after the 10th tDCS session).
We reported a significant 26.4% (±15.8) decrease of Y-BOCS score (p=0.002). The beneficial effect lasted during the 3month follow-up. No effect of tDCS was observed on depressive symptoms. At end point, 5 out of 8 patients had a decrease of ≥25%; and 3 out of 8 patients had a decrease of ≥35% in Y-BOCS score. tDCS was well tolerated.
tDCS with the cathode placed over the left OFC combined with the anode placed over the right cerebellum is a suitable and safe approach to decrease OCD symptoms in patients with treatment-resistant OCD. Large scale randomized controlled studies are needed to confirm this promising result.
•Combination of tDCS and SSRI can alleviate treatment-resistant OCD symptoms.•Targeting the OFC and the cerebellum is suitable and safe for patients with OCD.•Effects of tDCS on OCD symptoms can last at least 3months.
► Toxicokinetics (TK) is a key element to integrate the results from in silico, in vitro and in vivo studies. ► TK is needed to estimate target organ doses expected from realistic human external ...exposure scenarios. ► TK is necessary for quantitative in vitro–in vivo extrapolation (IVIVE). ► Physiologically based toxicokinetic modelling (PBTK) is the most adequate approach to simulate human TK. ► PBTK models are mechanism-based, but high-quality in vitro and in silico data is necessary for their success.
Toxicokinetics (TK) is the endpoint that informs about the penetration into and fate within the body of a toxic substance, including the possible emergence of metabolites. Traditionally, the data needed to understand those phenomena have been obtained in vivo. Currently, with a drive towards non-animal testing approaches, TK has been identified as a key element to integrate the results from in silico, in vitro and already available in vivo studies. TK is needed to estimate the range of target organ doses that can be expected from realistic human external exposure scenarios. This information is crucial for determining the dose/concentration range that should be used for in vitro testing. Vice versa, TK is necessary to convert the in vitro results, generated at tissue/cell or sub-cellular level, into dose response or potency information relating to the entire target organism, i.e. the human body (in vitro–in vivo extrapolation, IVIVE). Physiologically based toxicokinetic modelling (PBTK) is currently regarded as the most adequate approach to simulate human TK and extrapolate between in vitro and in vivo contexts. The fact that PBTK models are mechanism-based which allows them to be ‘generic’ to a certain extent (various extrapolations possible) has been critical for their success so far. The need for high-quality in vitro and in silico data on absorption, distribution, metabolism as well as excretion (ADME) as input for PBTK models to predict human dose–response curves is currently a bottleneck for integrative risk assessment.
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