Stem cells that naturally reside in adult tissues, such as muscle stem cells (MuSCs), exhibit robust regenerative capacity in vivo that is rapidly lost in culture. Using a bioengineered substrate to ...recapitulate key biophysical and biochemical niche features in conjunction with a highly automated single-cell tracking algorithm, we show that substrate elasticity is a potent regulator of MuSC fate in culture. Unlike MuSCs on rigid plastic dishes (approximately 10⁶ kilopascals), MuSCs cultured on soft hydrogel substrates that mimic the elasticity of muscle (12 kilopascals) self-renew in vitro and contribute extensively to muscle regeneration when subsequently transplanted into mice and assayed histologically and quantitatively by noninvasive bioluminescence imaging. Our studies provide novel evidence that by recapitulating physiological tissue rigidity, propagation of adult muscle stem cells is possible, enabling future cell-based therapies for muscle-wasting diseases.
Summary
The identification of inflammatory mediators in tear fluid have been used in ocular allergy: (a) to identify a ‘disease marker’; (b) to understand the immune mechanisms involved; (c) to ...correlate the severity of the disease; (d) to identify potential targets for therapeutic interventions; (e) as an indicator of treatment outcomes. Limitations of these findings are the lack of extensive validation of candidate biomarkers and the lack of determination of the specificity of the candidate markers. The increased concentrations of mast cell derived mediators in tears, such as tryptase and histamine, have been considered biomarkers of allergic IgE‐mediated response, while ECP levels is considered a specific biomarker of both allergic IgE‐ and non‐IgE‐mediated allergic conjunctivitis. The increased production and activation of cytokines, growth factors, imbalance between MMPs and TIMPs, are all involved in the pathogenesis of conjunctival inflammation, remodeling and corneal changes typical of chronic severe allergies. It is possible that patients with diseases can have a different protein profile and, therefore, protein or peptide analysis can be used as a possible fingerprint for disease biomarkers and pathological molecule identification.
Ocular allergy includes several clinically different conditions that can be considered as hypersensitivity disorders of the ocular surface. The classification of these conditions is complex, and ...their epidemiology has not been adequately studied because of the lack of unequivocal nomenclature. Ocular allergy symptoms are often, but not always, associated with other allergic manifestations, mostly rhinitis. However, specific ocular allergic diseases need to be recognized and managed by a team that includes both an ophthalmologist and an allergist. The diagnosis of ocular allergy is usually based on clinical history and signs and symptoms, with the support of in vivo and in vitro tests when the identification of the specific allergic sensitization is required for patient management. The aims of this Task Force Report are (i) to unify the nomenclature and classification of ocular allergy, by combining the ophthalmology and allergy Allergic Rhinitis and its Impact on Asthma criteria; (ii) to describe current methods of diagnosis; (iii) to summarize the therapeutic options for the management of ocular allergic inflammation.
Silicon nanowires are held and manipulated in controlled optical traps based on counter-propagating beams focused by low numerical aperture lenses. The double-beam configuration compensates light ...scattering forces enabling an in-depth investigation of the rich dynamics of trapped nanowires that are prone to both optical and hydrodynamic interactions. Several polarization configurations are used, allowing the observation of optical binding with different stable structure as well as the transfer of spin and orbital momentum of light to the trapped silicon nanowires. Accurate modeling based on Brownian dynamics simulations with appropriate optical and hydrodynamic coupling confirms that this rich scenario is crucially dependent on the non-spherical shape of the nanowires. Such an increased level of optical control of multiparticle structure and dynamics open perspectives for nanofluidics and multi-component light-driven nanomachines.
Abstract Background Transcaval access may enable fully percutaneous transcatheter aortic valve replacement (TAVR) without the hazards and discomfort of transthoracic (transapical or transaortic) ...access. Objectives We performed a prospective, independently-adjudicated, multi-center, single-arm Investigational Device Exemption trial of transcaval access for TAVR in patients ineligible for femoral artery access and high or prohibitive risk of complications from transthoracic access. Methods 100 subjects underwent attempted percutaneous transcaval access to the abdominal aorta by electrifying a caval guidewire and advancing into a prepositioned aortic snare. After exchanging for a rigid guidewire, conventional TAVR was performed through transcaval introducer sheaths. Transcaval access ports were closed with nitinol cardiac occluders. A core lab analyzed pre-discharge and 30-day abdominal CT. The STS predicted risk of mortality was 9.6 ± 6.3%. Results Transcaval access was successful in 99/100 subjects. Device success (access and closure with a nitinol cardiac occluder without death or emergency surgical rescue) was 98/99, except for one closed only with a covered stent. Inpatient survival was 96% and 30-day survival was 92%. VARC2 life-threatening bleeding and modified VARC2 major vascular complications possibly related to transcaval access were 7% and 13%, respectively. Median length of stay was 4 (2-6) days. There were no vascular complications after discharge. Conclusion Transcaval access enabled TAVR in patients who were not good candidates for transthoracic access. Bleeding and vascular complications, using permeable nitinol cardiac occluders to close the access ports, were common but acceptable in this high risk cohort. Transcaval access should be investigated in patients who are eligible for transthoracic access. Purpose-built closure devices are in development that may simplify the procedure and reduce bleeding.
Epidemiological studies suggest that dietary intake of vitamins A, C and E may be associated with the occurrence of asthma. A systematic review and meta-analysis was conducted in accordance with ...MOOSE guidelines to determine whether vitamins A, C and E, measured as dietary intakes or serum levels, are associated with asthma.
MEDLINE, EMBASE, CINAHL, CAB abstracts and AMED (up to November 2007), conference proceedings and bibliographies of papers were searched to identify studies of asthma, wheeze or airway responsiveness in relation to intakes and serum concentrations of vitamins A, C and E. Pooled odds ratios (OR) or mean differences (MD) with 95% confidence intervals (CI) were estimated using random effects models.
A total of 40 studies were included. Dietary vitamin A intake was significantly lower in people with asthma than in those without asthma (MD -82 microg/day, 95% CI -288 to -75; 3 studies) and in people with severe asthma than in those with mild asthma (MD -344 microg/day; 2 studies). Lower quantile dietary intakes (OR 1.12, 95% CI 1.04 to 1.21; 9 studies) and serum levels of vitamin C were also associated with an increased odds of asthma. Vitamin E intake was generally unrelated to asthma status but was significantly lower in severe asthma than in mild asthma (MD -1.20 microg/day, 95% CI -2.3 to -0.1; 2 studies).
Relatively low dietary intakes of vitamins A and C are associated with statistically significant increased odds of asthma and wheeze. Vitamin E intake does not appear to be related to asthma status.
Allergy and the eye Leonardi, A; Motterle, L; Bortolotti, M
Clinical and experimental immunology,
September 2008, Letnik:
153, Številka:
Supplement_1
Journal Article
Recenzirano
Odprti dostop
The eye represents an ideal and frequent site for the allergic reactions. The term 'allergic conjunctivitis' refers to a collection of disorders that affect the lid, conjunctiva and/or cornea. Even ...though the diagnosis is essentially clinical, local tests such as cytology, conjunctival provocation and tear mediator analysis can be performed. The immunoglobulin E (IgE)-mediated mechanism does not explain completely the severity and the clinical course of chronic allergic ocular diseases such as vernal (VKC) and atopic keratoconjunctivitis (AKC), which are probably also related to T cell-mediated responses, massive eosinophil attraction and activation and non-specific hypersensitivity. An altered balance between T helper type 1 (Th1) and Th2 cells and between Th1- and Th2-types of cytokines is thought to be responsible of the development of ocular allergic disorders. New findings suggest that a wide range of cytokines, chemokines, proteases and growth factors are involved by complex interwoven interactions rather than distinct and parallel pathways. In addition, several non-specific enzymatic systems may be activated during acute and chronic allergic inflammation, thus contributing to the complex pathogenesis of the disease. Current drug treatment for ocular allergy targets the key mechanisms involved in the development of clinical disease: mast cells with mast cell stabilizers, histamine with histamine receptor antagonists and inflammation with corticosteroids, severe inflammation with immunomodulators. None of these agents lacks side effects and none abolishes signs and symptoms completely. New therapeutic strategies are still needed to respond to the complex pathogenesis of severe forms of ocular allergy such as VKC and AKC.
Boulders often accumulate at the fronts of fast-flowing steep creek hazards. To trap these boulders, slit dams are commonly installed along steep creeks. An outstanding challenge when designing such ...dams lies in estimating the load exerted by a cluster of boulders: Clusters may exhibit discrete or continuum loading behavior, depending on their size. In this study, a physical flume test was carried out and the obtained results were used to calibrate a discrete element method (DEM) model. The DEM was then used to carry out a parametric study as a function of grain size, slit width and the channel slope. Results reveal that for continuum-like flows, the pressure near the slit of a slit dam can be almost double than elsewhere on the slit dam, as quantified using a newly proposed dimensionless ratio. For discrete flows, impact forces near the slit are more than double than elsewhere, thus representing a critical case for slit dam design. The concentration of forces near the slit necessitates designing for loads 2–3 times that of the rest of the slit dam to avoid wearing. (If wearing occurs, the slit width will increase, along with the volume of discharge, a potentially catastrophic scenario.) Furthermore, two dimensionless weighting coefficients that distinguish pressure from continuum-like flows and discrete impacts are proposed and evaluated. These coefficients can be incorporated into existing analytic expressions used by engineers.
Granular flows are typically studied in laboratory flumes based on common similarity scaling, which create stress fields that only roughly approximate field conditions. The geotechnical centrifuge ...produces stress conditions that are closer to those observed in the field, but steady conditions can be hardly achieved. Moreover, secondary effects induced by the apparent Coriolis acceleration, which can either dilate or compress the flow, often obscure scaling. This work aims at studying a set of numerical experiments where the effects of the Coriolis acceleration are measured and analyzed. Three flow states are observed: dense, dilute, and unstable. It is found that flows generated under the influence of dilative Coriolis accelerations are likely to become unstable. Nevertheless, a steady dense flow can still be obtained if a large centrifuge is used. A parametric group is proposed to predict the insurgence of instabilities; this parameter can guide experimental designs and could help to avoid damage to the experimental apparatus and model instrumentation.
Graphic abstract
Nearly identical Pd nanocubes yield an x-ray powder diffraction pattern with interference fringes affording access to unprecedented structural details of nanocrystal size, shape, and complex atomic ...displacement for a billion-sized population. The excellent agreement between diffraction data and molecular dynamics (MD) provides strong experimental validation of MD simulations and the proposed data-interpretation paradigm. These results show that individual atomic displacements within the nanocubes are not only a function of disrupted bonds and the crystallographic plane of the adjacent surface, but are complex strain gradients extending across all surfaces of the particle strongly influenced by atomic displacements. This observation of nonuniform surface strain and the manner in which it is affected by different sizes, shapes, and locations within each facet could be the key to understanding many surface related properties of shaped nanocrystals including those associated with important catalysis applications.
PDF
