Wall shear stress at the initiation site of cerebral aneurysms

Hemodynamics are believed to play an important role in the initiation of cerebral aneurysms. In particular, studies have focused on wall shear stress (WSS), which is a key regulator of vascular biology and pathology. In line with the observation that aneurysms predominantly occur at regions of high WSS, such as bifurcation apices or outer walls of vascular bends, correlations have been found between the aneurysm initiation site and high WSS. The aim of our study was to analyze the WSS field at an aneurysm initiation site that was neither a bifurcation apex nor the outer wall of a vascular bend. Ten cases with aneurysms on the A1 segment of the anterior cerebral artery were analyzed and compared with ten controls. Aneurysms were virtually removed from the vascular models of the cases to mimic the pre-aneurysm geometry. Computational fluid dynamics (CFD) simulations were created to assess the magnitude, gradient, multidirectionality, and pulsatility of the WSS. To aid the inter-subject comparison of hemodynamic variables, we mapped the branch surfaces onto a two-dimensional parametric space. This approach made it possible to view the whole branch at once for qualitative evaluation. It also allowed us to empirically define a patch for quantitative analysis, which was consistent among subjects and encapsulated the aneurysm initiation sites in our dataset. To test the sensitivity of our results, CFD simulations were repeated with a second independent observer virtually removing the aneurysms and with a 20 % higher flow rate at the inlet. We found that branches harboring aneurysms were characterized by high WSS and high WSS gradients. Among all assessed variables, the aneurysm initiation site most consistently coincided with peaks of temporal variation in the WSS magnitude

Are All Placebo Effects Equal? Placebo Pills, Sham Acupuncture, Cue Conditioning and Their Association

Placebo treatments and healing rituals have been used to treat pain throughout history. The present within-subject crossover study examines the variability in individual responses to placebo treatment with verbal suggestion and visual cue conditioning by investigating whether responses to different types of placebo treatment, as well as conditioning responses, correlate with one another. Secondarily, this study also examines whether responses to sham acupuncture correlate with responses to genuine acupuncture. Healthy subjects were recruited to participate in two sequential experiments. Experiment one is a five-session crossover study. In each session, subjects received one of four treatments: placebo pills (described as Tylenol), sham acupuncture, genuine acupuncture, or no treatment rest control condition. Before and after each treatment, paired with a verbal suggestion of positive effect, each subject's pain threshold, pain tolerance, and pain ratings to calibrated heat pain were measured. At least 14 days after completing experiment one, all subjects were invited to participate in experiment two, during which their analgesic responses to conditioned visual cues were tested. Forty-eight healthy subjects completed experiment one, and 45 completed experiment two. The results showed significantly different effects of genuine acupuncture, placebo pill and rest control on pain threshold. There was no significant association between placebo pills, sham acupuncture and cue conditioning effects, indicating that individuals may respond to unique healing rituals in different ways. This outcome suggests that placebo response may be a complex behavioral phenomenon that has properties that comprise a state, rather than a trait characteristic. This could explain the difficulty of detecting a signature for “placebo responders.” However, a significant association was found between the genuine and sham acupuncture treatments, implying that the non-specific effects of acupuncture may contribute to the analgesic effect observed in genuine acupuncture analgesia.National Center for Complementary and Alternative Medicine (U.S.) (R01AT005280

People’s understanding of verbal risk descriptors in patient information leaflets : a cross-sectional national survey of 18- to 65-year-olds in England

Introduction Evidence suggests the current verbal risk descriptors used to communicate side effect risk in patient information leaflets (PILs) are overestimated. Objectives The aim was to establish how people understand the verbal risk descriptors recommended for use in PILs by the European Commission (EC), and alternative verbal risk descriptors, in the context of mild and severe side effects. Methods A cross-sectional online survey was carried out by a market research company recruiting participants aged between 18 and 65 years living in England. Data were collected between 18 March and 1 April 2016. Participants were given a hypothetical scenario regarding the risk of mild or severe medication side effects and asked to estimate how many out of 10,000 people would be affected for each of the verbal risk descriptors being tested. Results A total of 1003 participants were included in the final sample. The risks conveyed by the EC recommended verbal risk descriptors were greatly overestimated by participants. Two distinct distributions were apparent for participant estimates of side effect risks: those for ‘high risk’ verbal descriptors (e.g. ‘common’, ‘likely’, ‘high chance’) and those for ‘low risk’ verbal descriptors (e.g. ‘uncommon’, ‘unlikely’, ‘low chance’). Within these two groups, the distributions were near to identical regardless of what adverb (e.g. very, high, fair) or adjective (e.g. common, likely, chance) was used. The EC recommended verbal risk descriptors were more likely to be understood in accordance with their intended meanings when describing severe side effects. Very few demographic or psychological factors were consistently associated with how well participants understood the EC recommended verbal risk descriptors. Discussion The current verbal risk descriptors used in PILs are ineffective at best and misleading at worst. Discontinuing the use of verbal risk descriptors would limit the likelihood of people overestimating the risk of side effects

Molecular mechanism of edema formation in nephrotic syndrome: therapeutic implications

Sodium retention and edema are common features of nephrotic syndrome that are classically attributed to hypovolemia and activation of the renin–angiotensin–aldosterone system. However, numbers of clinical and experimental findings argue against this underfill theory. In this review we analyze data from the literature in both nephrotic patients and experimental models of nephrotic syndrome that converge to demonstrate that sodium retention is not related to the renin–angiotensin–aldosterone status and that fluid leakage from capillary to the interstitium does not result from an imbalance of Starling forces, but from changes of the intrinsic properties of the capillary endothelial filtration barrier. We also discuss how most recent findings on the cellular and molecular mechanisms of sodium retention has allowed the development of an efficient treatment of edema in nephrotic patients

Aquaporin water channels in the nervous system.

The aquaporins (AQPs) are plasma membrane water-transporting proteins. AQP4 is the principal member of this protein family in the CNS, where it is expressed in astrocytes and is involved in water movement, cell migration and neuroexcitation. AQP1 is expressed in the choroid plexus, where it facilitates cerebrospinal fluid secretion, and in dorsal root ganglion neurons, where it tunes pain perception. The AQPs are potential drug targets for several neurological conditions. Astrocytoma cells strongly express AQP4, which may facilitate their infiltration into the brain, and the neuroinflammatory disease neuromyelitis optica is caused by AQP4-specific autoantibodies that produce complement-mediated astrocytic damage

From Architectured Materials to Large-Scale Additive Manufacturing

The classical material-by-design approach has been extensively perfected by materials scientists, while engineers have been optimising structures geometrically for centuries. The purpose of architectured materials is to build bridges across themicroscale ofmaterials and themacroscale of engineering structures, to put some geometry in the microstructure. This is a paradigm shift. Materials cannot be considered monolithic anymore. Any set of materials functions, even antagonistic ones, can be envisaged in the future. In this paper, we intend to demonstrate the pertinence of computation for developing architectured materials, and the not-so-incidental outcome which led us to developing large-scale additive manufacturing for architectural applications

Computational Homogenization of Architectured Materials

Architectured materials involve geometrically engineered distributions of microstructural phases at a scale comparable to the scale of the component, thus calling for new models in order to determine the effective properties of materials. The present chapter aims at providing such models, in the case of mechanical properties. As a matter of fact, one engineering challenge is to predict the effective properties of such materials; computational homogenization using finite element analysis is a powerful tool to do so. Homogenized behavior of architectured materials can thus be used in large structural computations, hence enabling the dissemination of architectured materials in the industry. Furthermore, computational homogenization is the basis for computational topology optimization which will give rise to the next generation of architectured materials. This chapter covers the computational homogenization of periodic architectured materials in elasticity and plasticity, as well as the homogenization and representativity of random architectured materials