Prophylactic corneal crosslinking in myopic small-incision lenticule extraction - Long-term visual and refractive outcomes

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Computerized Generation and Finite Element Stress Analysis of Endodontic Rotary Files

Introduction: The finite element method has been extensively used to analyze the mechanical behavior of endodontic rotary files under bending and torsional conditions. This methodology requires elevated computer-aided design skills to reproduce the geometry of the endodontic file, and also mathematical knowledge to perform the finite element analysis. In this study, an automated procedure is proposed for the computerized generation and finite element analysis of endodontic rotary files under bending and torsional conditions. Methods: An endodontic rotary file with a 25mm total length, 0.25mm at the tip, 1.20mm at 16mm from the tip, 2mm pitch and squared cross section was generated using the proposed procedure and submitted for analysis under bending and torsional conditions by clamping the last 3mm of the endodontic rotary file and applying a transverse load of 0.1N and a torsional moment of 0.3N.cm. Results: The results of the finite element analyses showed a maximum von Mises stress of 398MPa resulting from the bending analysis and a maximum von Mises stress of 843MPa resulting from the torsional analysis, both of which are next to the encastre point. Conclusions: The automated procedure allows an accurate description of the geometry of the endodontic file to be obtained based on its design parameters as well as a finite element model of the endodontic file from the previously generated geometry

Junctophilin-2 tethers T-tubules and recruits functional L-type calcium channels to lipid rafts in adult cardiomyocytes

Aim: In cardiomyocytes, transverse tubules (T-tubules) associate with the sarcoplasmic reticulum (SR), forming junctional membrane complexes (JMCs) where L-type calcium channels (LTCCs) are juxtaposed to Ryanodine receptors (RyR). Junctophilin-2 (JPH2) supports the assembly of JMCs by tethering T-tubules to the SR membrane. T-tubule remodeling in cardiac diseases is associated with down-regulation of JPH2 expression suggesting that JPH2 plays a crucial role in T-tubule stability. Furthermore, increasing evidence indicate that JPH2 might additionally act as a modulator of calcium signaling by directly regulating RyR and LTCCs. This study aimed at determining whether JPH2 overexpression restores normal T-tubule structure and LTCC function in cultured cardiomyocytes. Methods and results: Rat ventricular myocytes kept in culture for 4 days showed extensive T-tubule remodeling with impaired JPH2 localization and relocation of the scaffolding protein Caveolin3 (Cav3) from the T-tubules to the outer membrane. Overexpression of JPH2 restored T-tubule structure and Cav3 relocation. Depletion of membrane cholesterol by chronic treatment with Methyl-β-cyclodextrin (MβCD) countered the stabilizing effect of JPH2 overexpression on T-tubules and Cav3. Super-resolution scanning patch-clamp showed that JPH2 overexpression greatly increased the number of functional LTCCs at the plasma membrane. Treatment with MβCD reduced LTCC open probability and activity. Proximity ligation assays showed that MβCD did not affect JPH2 interaction with RyR and the pore-forming LTCC subunit Cav1.2, but strongly impaired JPH2 association with Cav3 and the accessory LTCC subunit Cavβ2. Conclusions: JPH2 promotes T-tubule structural stability and recruits functional LTCCs to the membrane, most likely by directly binding to the channel. Cholesterol is involved in the binding of JPH2 to T-tubules as well as in the modulation of LTCC activity. We propose a model where cholesterol and Cav3 support the assembly of lipid rafts which provide an anchor for JPH2 to form JMCs and a platform for signaling complexes to regulate LTCC activity

EVIDENT 3 Study: A randomized, controlled clinical trial to reduce inactivity and caloric intake in sedentary and overweight or obese people using a smartphone application: Study protocol

Introduction: Mobile technology, when included within multicomponent interventions, could contribute to more effective weight loss. The objective of this project is to assess the impact of adding the use of the EVIDENT 3 application, designed to promote healthy living habits, to traditional modification strategies employed for weight loss. Other targeted behaviors (walking, caloric-intake, sitting time) and outcomes (quality of life, inflammatory markers, measurements of arterial aging) will also be evaluated. Methods: Randomized, multicentre clinical trial with 2 parallel groups. The study will be conducted in the primary care setting and will include 700 subjects 20 to 65 years, with a body mass index (27.5-40kg/m2), who are clinically classified as sedentary. The primary outcome will be weight loss. Secondary outcomes will include change in walking (steps/d), sitting time (min/wk), caloric intake (kcal/d), quality of life, arterial aging (augmentation index), and pro-inflammatory marker levels. Outcomes will be measured at baseline, after 3 months, and after 1 year. Participants will be randomly assigned to either the intervention group (IG) or the control group (CG). Both groups will receive the traditional primary care lifestyle counseling prior to randomization. The subjects in the IG will be lent a smartphone and a smartband for a 3-month period, corresponding to the length of the intervention. The EVIDENT 3 application integrates the information collected by the smartband on physical activity and the self-reported information by participants on daily food intake. Using this information, the application generates recommendations and personalized goals for weight loss. Discussion: There is a great diversity in the applications used obtaining different results on lifestyle improvement and weight loss. The populations studied are not homogeneous and generate different results. The results of this study will help our understanding of the efficacy of new technologies, combined with traditional counseling, towards reducing obesity and enabling healthier lifestyles. Ethicsanddissemination: The study was approved by the Clinical Research Ethics Committee of the Health Area of Salamanca ("CREC of Health Area of Salamanca") on April 2016. A SPIRIT checklist is available for this protocol. The trial was registered in ClinicalTrials.gov provided by the US National Library of Medicine-number NCT03175614

Empirical agent-based modelling of everyday pro-environmental behaviours at work

We report on agent-based modelling work in the LOCAW project (Low Carbon at Work: Modelling Agents and Organisations to Achieve Transition to a Low Carbon Europe). The project explored the effectiveness of various backcasting scenarios conducted with case study organisations in bringing about pro-environmental change in the workforce in the domains of transport, energy use and waste. The model used qualitative representations of workspaces in formalising each scenario, and decision trees learned from questionnaire responses to represent decision-making. We describe the process by which the decision trees were constructed, noting that the use of decision trees in agent-based models requires particular considerations owing to the potential use of explanatory variables in model dynamics. The results of the modelling in various scenarios emphasise the importance of structural environmental changes in facilitating everyday pro-environmental behaviour, but also show there is a role for psychological variables such as norms, values and efficacy. As such, the topology of social interactions is a potentially important driver, raising the interesting prospect that both workplace geography and organisational hierarchy have a role to play in influencing workplace pro-environmental behaviours

Phenotypic, transcriptomic, and genomic features of clonal plasma cells in light-chain amyloidosis

Immunoglobulin light-chain amyloidosis (AL) and multiple myeloma (MM) are 2 distinct monoclonal gammopathies that involve the same cellular compartment: clonal plasma cells (PCs). Despite the fact that knowledge about MM PC biology has significantly increased in the last decade, the same does not apply for AL. Here, we used an integrative phenotypic, molecular, and genomic approach to study clonal PCs from 24 newly diagnosed patients with AL. Through principal-component-analysis, we demonstrated highly overlapping phenotypic profiles between AL and both monoclonal gammopathy of undetermined significance and MM PCs. However, in contrast to MM, highly purified fluorescence-activated cell-sorted clonal PCs from AL (n = 9) showed almost normal transcriptome, with only 38 deregulated genes vs normal PCs; these included a few tumor-suppressor (CDH1, RCAN) and proapoptotic (GLIPR1, FAS) genes. Notwithstanding, clonal PCs in AL (n=11) were genomically unstable, with a median of 9 copy number alterations (CNAs) per case, many of such CNAs being similar to those found in MM. Whole-exome sequencing (WES) performed in 5 AL patients revealed a median of 15 nonrecurrent mutations per case. Altogether, our results show that in the absence of a unifying mutation by WES, clonal PCs in AL display phenotypic and CNA profiles similar to MM, but their transcriptome is remarkably similar to that of normal PCs

CALIFA, the Calar Alto Legacy Integral Field Area survey: I. Survey presentation

We present here the Calar Alto Legacy Integral Field Area (CALIFA) survey, which has been designed to provide a first step in this direction.We summarize the survey goals and design, including sample selection and observational strategy.We also showcase the data taken during the first observing runs (June/July 2010) and outline the reduction pipeline, quality control schemes and general characteristics of the reduced data. This survey is obtaining spatially resolved spectroscopic information of a diameter selected sample of $\sim600$ galaxies in the Local Universe (0.005< z <0.03). CALIFA has been designed to allow the building of two-dimensional maps of the following quantities: (a) stellar populations: ages and metallicities; (b) ionized gas: distribution, excitation mechanism and chemical abundances; and (c) kinematic properties: both from stellar and ionized gas components. CALIFA uses the PPAK Integral Field Unit (IFU), with a hexagonal field-of-view of \sim1.3\sq\arcmin', with a 100% covering factor by adopting a three-pointing dithering scheme. The optical wavelength range is covered from 3700 to 7000 {\AA}, using two overlapping setups (V500 and V1200), with different resolutions: R\sim850 and R\sim1650, respectively. CALIFA is a legacy survey, intended for the community. The reduced data will be released, once the quality has been guaranteed. The analyzed data fulfill the expectations of the original observing proposal, on the basis of a set of quality checks and exploratory analysis. We conclude from this first look at the data that CALIFA will be an important resource for archaeological studies of galaxies in the Local Universe.Comment: 32 pages, 29 figures, Accepted for publishing in Astronomy and Astrophysic