Epithelial-mesenchymal transdifferentiation in pediatric lens epithelial cells

PURPOSE. Posterior capsule opacification (PCO) is a complication after cataract surgery, particularly in children. Epithelial-mesenchymal transition (EMT) of lens epithelial cells, mediated by transforming growth factor beta (TGF beta), contributes to PCO. However, its pathogenesis in children is poorly understood. We correlated cell growth in culture with patient characteristics, studied gene expression of pediatric lens epithelial cells (pLEC), and examined the effects of TGF beta-2 on these cells in vitro. METHODS. Clinical characteristics of children with cataracts correlated with growth behavior of pLEC in vitro. mRNA expression of epithelial (alpha B-crystallin, connexin-43) and mesenchymal (alpha(V)-integrin, alpha-smooth muscle actin, collagen-I alpha 2, fibronectin-1) markers was quantified in pLEC and in cell line HLE-B3 in the presence and absence of TGF beta-2. RESULTS. Fifty-four anterior lens capsules from 40 children aged 1 to 180 months were obtained. Cell outgrowth occurred in 44% of the capsules from patients <= 12 months and in 33% of capsules from children aged 13 to 60 months, but in only 6% of capsules from children over 60 months. TGF beta-2 significantly upregulated expression of alpha B-crystallin (HLE-B3), alpha(V)-integrin (HLE-B3), collagen-I alpha 2, and fibronectin-1 (in pLEC and HLE-B3 cells). CONCLUSIONS. Patient characteristics correlated with growth behavior of pLEC in vitro, paralleling a higher clinical incidence of PCO in younger children. Gene expression profiles of pLEC and HLE-B3 suggest that upregulation of alpha(V)-integrin, collagen-I alpha 2, and fibronectin-1 are involved in EMT

Concentration Dependence of Superconductivity and Order-Disorder Transition in the Hexagonal Rubidium Tungsten Bronze RbxWO3. Interfacial and bulk properties

We revisited the problem of the stability of the superconducting state in RbxWO3 and identified the main causes of the contradictory data previously published. We have shown that the ordering of the Rb vacancies in the nonstoichiometric compounds have a major detrimental effect on the superconducting temperature Tc.The order-disorder transition is first order only near x = 0.25, where it cannot be quenched effectively and Tc is reduced below 1K. We found that the high Tc's which were sometimes deduced from resistivity measurements, and attributed to compounds with .25 < x < .30, are to be ascribed to interfacial superconductivity which generates spectacular non-linear effects. We also clarified the effect of acid etching and set more precisely the low-rubidium-content boundary of the hexagonal phase.This work makes clear that Tc would increase continuously (from 2 K to 5.5 K) as we approach this boundary (x = 0.20), if no ordering would take place - as its is approximately the case in CsxWO3. This behaviour is reminiscent of the tetragonal tungsten bronze NaxWO3 and asks the same question : what mechanism is responsible for this large increase of Tc despite the considerable associated reduction of the electron density of state ? By reviewing the other available data on these bronzes we conclude that the theoretical models which are able to answer this question are probably those where the instability of the lattice plays a major role and, particularly, the model which call upon local structural excitations (LSE), associated with the missing alkali atoms.Comment: To be published in Physical Review

The influence of cycloplegic in objective refraction

The purpose of this study was to compare refractions measured with an autorefractor and retinoscopy in cycloplegic and non-cycloplegic eyes. The objective refractions were performed in 199 right eyes from 199 healthy young adults with a mean age of 21.6 ±2.66 years. The measurements were performed first without cycloplegia and repeated 30 minutes later with cycloplegia. Data were analyzed using Fourier decomposition of the power profile. More negative values of component M and J0 were give by non-cycloplegic autorefraction compared to cycloplegic autorefraction (p<0.001). However more positive values were given by non-cycloplegic autorefraciton regarding to the J45 vector, althought this differences were not statistically significant (p=0.233). Regarding retinoscopy, more negative values of component M where obtained with non-cycloplegic retinoscopy (p<0.001); for the cylindrical vectors J0 and J45 the retinoscopy without cycloplegic yields more negative values (p= 0.234; p= 0.112, respectively). Accepting that differences between cycloplegic and non-cycloplegic retinoscopy are only due to accommodative response, present results confirm that when performed by an experienced clinician, retinoscopy is a more reliable method to obtain objective start point for refraction under non-cycloplegic conditions

Synthesis and characterization of high-affinity 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene-labeled fluorescent ligands for human β-adrenoceptors

The growing practice of exploiting noninvasive fluorescence-based techniques to study G protein-coupled receptor pharmacology at the single cell and single molecule level demands the availability of high-quality fluorescent ligands. To this end, this study evaluated a new series of red-emitting ligands for the human β-adrenoceptor family. Upon the basis of the orthosteric ligands propranolol, alprenolol, and pindolol, the synthesized linker-modified congeners were coupled to the commercially available fluorophore BODIPY 630/650-X. This yielded high-affinity β-adrenoceptor fluorescent ligands for both the propranolol and alprenolol derivatives; however, the pindolol-based products displayed lower affinity. A fluorescent diethylene glycol linked propranolol derivative (18a) had the highest affinity (log KD of -9.53 and -8.46 as an antagonist of functional β2- and β1-mediated responses, respectively). Imaging studies with this compound further confirmed that it can be employed to selectively label the human β2-adrenoceptor in single living cells, with receptor-associated binding prevented by preincubation with the nonfluorescent β2-selective antagonist 3-(isopropylamino)-1-[(7-methyl-4-indanyl)oxy]-butan-2-ol (ICI 118551) (J. Cardiovasc. Pharmacol. 1983, 5, 430-437.

Comprehensive assessments and related interventions to enhance the long-term outcomes of child, adolescent and young adult cancer survivors – presentation of the CARE for CAYA-Program study protocol and associated literature review

Background Improved, multimodal treatment strategies have been shown to increase cure rates in cancer patients. Those who survive cancer as a child, adolescent or young adult (CAYA), are at a higher risk for therapy-, or disease-related, late or long-term effects. The CARE for CAYA-Program has been developed to comprehensively assess any potential future problems, to offer need-based preventative interventions and thus to improve long-term outcomes in this particularly vulnerable population. Methods The trial is designed as an adaptive trial with an annual comprehensive assessment followed by needs stratified, modular interventions, currently including physical activity, nutrition and psycho-oncology, all aimed at improving the lifestyle and/or the psychosocial situation of the patients. Patients, aged 15–39 years old, with a prior cancer diagnosis, who have completed tumour therapy and are in follow-up care, and who are tumour free, will be included. At baseline (and subsequently on an annual basis) the current medical and psychosocial situation and lifestyle of the participants will be assessed using a survey compiled of various validated questionnaires (e.g. EORTC QLQ C30, NCCN distress thermometer, PHQ-4, BSA, nutrition protocol) and objective parameters (e.g. BMI, WHR, co-morbidities like hyperlipidaemia, hypertension, diabetes), followed by basic care (psychological and lifestyle consultation). Depending on their needs, CAYAs will be allocated to preventative interventions in the above-mentioned modules over a 12-month period. After 1 year, the assessment will be repeated, and further interventions may be applied as needed. During the initial trial phase, the efficacy of this approach will be compared to standard care (waiting list with intervention in the following year) in a randomized study. During this phase, 530 CAYAs will be included and 320 eligible CAYAs who are willing to participate in the interventions will be randomly allocated to an intervention. Overall, 1500 CAYAs will be included and assessed. The programme is financed by the innovation fund of the German Federal Joint Committee and will be conducted at 14 German sites. Recruitment began in January 2018. Discussion CAYAs are at high risk for long-term sequelae. Providing structured interventions to improve lifestyle and psychological situation may counteract against these risk factors. The programme serves to establish uniform regular comprehensive assessments and need-based interventions to improve long-term outcome in CAYA survivors. Trial registration Registered at the German Clinical Trial Register (ID: DRKS00012504, registration date: 19th January 2018)

Análise espacial dos fatores da equação universal de perda de solo em área de nascentes

O objetivo deste trabalho foi avaliar a perda de solo de área de nascentes da Microbacia do Córrego do Tijuco, SP. Foi utilizada a análise espacial dos fatores da equação universal da perda de solo (EUPS), em integração com análise de componentes principais e geoestatística. A perda de solo média, estimada para a área, foi de 118,5 Mg ha‑1 por ano, considerada alta. Próximo à zona urbana, houve alta interação dos fatores erosividade da chuva e práticas conservacionistas, o que evidencia grande perda de solo, em razão da concentração da água proveniente da camada impermeabilizada urbana, com alta velocidade de escoamento. Nos divisores de águas, a atuação da erodibilidade foi proeminente, em contraste com o fator topográfico. Foram observadas áreas com atuação conjunta destes fatores, inclusive em locais de inclinação suave, porém com alto potencial natural de erosão. A interação das análises multivariadas e geoestatística permite a estratificação da área, identifica locais com propriedades específicas quanto à perda de solo, e espacializa os fatores do processo erosivo e suas interações ao longo do relevo

Evaluating expertise of knowledge workers through structural dimensional analysis of mental representation (SDA-M)

The role of superior human capital in creating and maintaining competitive advantage in the global marketplace is an increasing priority. The problem for business leaders is that despite the purported benefits of superior human capital, contemporary human capital assessments prove incapable of reliably identifying the best employees to hire, promote, or retain. Research into the use of mental models as a means to differentiate expert and novice performers suggested that a simple and reliable means of eliciting and comparing mental models might address this gap. Prior studies following the Structural Dimensional Analysis of Mental Representations (SDA-M) methodology produced reliable and repeatable differentiation of expert and novice performers in professional sports, but had not been applied to the knowledge-work driving today’s businesses. The purpose of this quantitative, quasi-experimental study was to evaluate the use of SDA-M in the identification and classification of expert knowledge workers. Specifically, this research sought to answer two specific research questions concerning the use of SDA-M: what is the similarity of expert knowledge worker mental models produced via SDA-M analysis; and, what is the similarity of novice knowledge worker mental models when compared to those of experts? Following the SDA-M methodology, customer support personnel purposefully selected to represent expert (n = 6) and novice (n = 6) performers completed a sorting task designed to elicit and record individual mental models of a critical job task. Experts were selected from senior-level positions with a minimum of five years organizational tenure; novices were selected from entry-level positions with no more than one year of organizational tenure. The individual mental models where then compared using Qsplit to determine the degree of similarity between them. SDA-M analysis proved ineffective at differentiating expert and novice performers on the study stimulus task. Although SDA-M analysis differentiated subjects into two groups, these groups did not align with the ex ante definitions of expert and novice performers. Additional analysis suggested an incompatibility between the job task selected for eliciting mental models and the criteria used in sampling; industry tenure proved a better indicator of expert performance of the study task than organizational tenure. Although the results of this study can only be considered inconclusive, SDA-M analysis demonstrated the ability to clearly differentiate participants based on the structure and consistency of their mental model constructions. Continued research into the use of SDA-M as a means to identify superior human capital is warranted