Impact of surface adhesion and sample heterogeneity on the multiscale mechanical characterisation of soft biomaterials

Funding from the Engineering and Physical Sciences Research Council (EP/L505602/1) is gratefully acknowledged

Measurements of Elastic Moduli of Silicone Gel Substrates with a Microfluidic Device

Thin layers of gels with mechanical properties mimicking animal tissues are widely used to study the rigidity sensing of adherent animal cells and to measure forces applied by cells to their substrate with traction force microscopy. The gels are usually based on polyacrylamide and their elastic modulus is measured with an atomic force microscope (AFM). Here we present a simple microfluidic device that generates high shear stresses in a laminar flow above a gel-coated substrate and apply the device to gels with elastic moduli in a range from 0.4 to 300 kPa that are all prepared by mixing two components of a transparent commercial silicone Sylgard 184. The elastic modulus is measured by tracking beads on the gel surface under a wide-field fluorescence microscope without any other specialized equipment. The measurements have small and simple to estimate errors and their results are confirmed by conventional tensile tests. A master curve is obtained relating the mixing ratios of the two components of Sylgard 184 with the resulting elastic moduli of the gels. The rigidity of the silicone gels is less susceptible to effects from drying, swelling, and aging than polyacrylamide gels and can be easily coated with fluorescent tracer particles and with molecules promoting cellular adhesion. This work can lead to broader use of silicone gels in the cell biology laboratory and to improved repeatability and accuracy of cell traction force microscopy and rigidity sensing experiments

The STRATOB study: design of a randomized controlled clinical trial of Cognitive Behavioral Therapy and Brief Strategic Therapy with telecare in patients with obesity and binge-eating disorder referred to residential nutritional rehabilitation

bstract BACKGROUND: Overweight and obesity are linked with binge eating disorder (BED). Effective interventions to significantly reduce weight, maintain weight loss and manage associated pathologies like BED are typically combined treatment options (dietetic, nutritional, physical, behavioral, cognitive-behavioral, pharmacological, surgical). Significant difficulties with regard to availability, costs, treatment adherence and long-term efficacy are present. Particularly Cognitive Behavioral Therapy (CBT) is the therapeutic approach indicated both in in-patient and in out-patient settings for BED. In recent years systemic and systemic-strategic psychotherapies have been implemented to treat patients with obesity and BED involved in familiar problems. Particularly a brief protocol for the systemic-strategic treatment of BED, using overall the strategic dialogue, has been recently developed. Moreover telemedicine, a new promising low cost method, has been used for obesity with BED in out-patient settings in order to avoid relapse after the in-patient step of treatment and to keep on a continuity of care with the involvement of the same clinical in-patient team. METHODS: The comparison between CBT and Brief Strategic Therapy (BST) will be assessed in a two-arm randomized controlled clinical trial. Due to the novelty of the application of BST in BED treatment (no other RCTs including BST have been carried out), a pilot study will be carried out before conducting a large scale randomized controlled clinical trial (RCT). Both CBT and BST group will follow an in-hospital treatment (diet, physical activity, dietitian counseling, 8 psychological sessions) plus 8 out-patient telephone-based sessions of psychological support and monitoring with the same in-patient psychotherapists. Primary outcome measure of the randomized trial will be the change in the Global Index of the Outcome Questionnaire (OQ-45.2). Secondary outcome measures will be the percentage of BED patients remitted considering the number of weekly binge episodes and the weight loss. Data will be collected at baseline, at discharge from the hospital (c.a. 1 month after) and after 6-12-24 months from the end of the in-hospital treatment. Data at follow-up time points will be collected through tele-sessions. DISCUSSION: The STRATOB (Systemic and STRATegic psychotherapy for OBesity), a comprehensive two-phase stepped down program enhanced by telepsychology for the medium-term treatment of obese people with BED seeking intervention for weight loss, will shed light about the comparison of the effectiveness of the BST with the gold standard CBT and about the continuity of care at home using a low-level of telecare (mobile phones). TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT0109625

Change in dominance determines herbivore effects on plant biodiversity

Herbivores alter plant biodiversity (species richness) in many of the world’s ecosystems, but the magnitude and the direction of herbivore effects on biodiversity vary widely within and among ecosystems. One current theory predicts that herbivores enhance plant biodiversity at high productivity but have the opposite effect at low productivity. Yet, empirical support for the importance of site productivity as a mediator of these herbivore impacts is equivocal. Here, we synthesize data from 252 large-herbivore exclusion studies, spanning a 20-fold range in site productivity, to test an alternative hypothesis—that herbivore-induced changes in the competitive environment determine the response of plant biodiversity to herbivory irrespective of productivity. Under this hypothesis, when herbivores reduce the abundance (biomass, cover) of dominant species (for example, because the dominant plant is palatable), additional resources become available to support new species, thereby increasing biodiversity. By contrast, if herbivores promote high dominance by increasing the abundance of herbivory-resistant, unpalatable species, then resource availability for other species decreases reducing biodiversity. We show that herbivore-induced change in dominance, independent of site productivity or precipitation (a proxy for productivity), is the best predictor of herbivore effects on biodiversity in grassland and savannah sites. Given that most herbaceous ecosystems are dominated by one or a few species, altering the competitive environment via herbivores or by other means may be an effective strategy for conserving biodiversity in grasslands and savannahs globally

Molding Micropatterns of Elasticity on PEG-Based Hydrogels to Control Cell Adhesion and Migration

We present an innovative and simple, soft UV lithographic method “FIll-Molding In Capillaries” (FIMIC) that combines soft lithography with capillary force driven filling of micro-channels to create smooth hydrogel substrates with a 2D micro-pattern on the surface. The lithographic procedure involves the molding of a polymer; in our case a bulk PEG-based hydrogel, via UV-curing from a microfabricated silicon master. The grooves of the created regular line pattern are consequently filled with a second hydrogel by capillary action. As a result, a smooth surface is obtained with a well-defined pattern design of the two different polymers on its surface. The FIMIC method is very versatile; the only prerequisite is that the second material is liquid before curing in order to enable the filling process. In this specific case we present the proof of principle of this method by applying two hydrogels which differ in their crosslinking density and therefore in their elasticity. Preliminary cell culture studies on the fabricated elasticity patterned hydrogels indicate the preferred adhesion of the cells to the stiffer regions of the substrates, which implies that the novel substrates are a very useful platform for systematic cell migration studies, e.g. more fundamental investigation of the concept of “durotaxis”

Quality of life in patients with craniocervical dystonia: Italian validation of the “Cervical Dystonia Impact Profile (CDIP-58)” and the “Craniocervical Dystonia Questionnaire (CDQ-24)”

Dystonia is a disabling and disfiguring disorder that can often affect many aspects of patients’ daily lives, and lower their self-esteem. To date, quality of life (QoL) has been assessed in dystonic patients using generic measures that do not address the specific problems of this diagnostic group. Recently, two disease-specific scales ‘‘The Cervical Dystonia Impact Profile (CDIP-58)’’ and the ‘‘Craniocervical Dystonia Questionnaire (CDQ-24)’’ were validated for measuring QoL in craniocervical dystonia patients. No disease- specific scales for QoL for dystonic patients are currently available in Italian. The aim of our study was to produce and validate the Italian version of the CDIP-58 and CDQ-24. We obtained the Italian version of CDQ-24 and CDIP-58 with a back-translation design. Both scales were applied to a population of 94 craniocervical dystonia patients along with the Short Form 36 health-survey questionnaire (SF-36), both before and 4 weeks after botulinum toxin therapy. A group of 65 controls matched for sex, age and comorbidity underwent the SF-36. Internal consistency was satisfactory for all subscales. Both the CDIP-58 and CDQ-24 showed moderate to high correlations with similar items of the SF-36. Sensitivity to change was confirmed by highly significant improvements in all CDQ-24 subscales and by moderate improvements in three out of eight CDIP-58 subscales and total score. This is the first Italian study on QoL in dystonia patients. We validated the Italian version of two disease-specific questionnaires to evaluate QoL in craniocervical dystonia patients. These scales could be useful for both clinical practice and clinical trials