Collagen and Stretch Modulate Autocrine Secretion of Insulin-like Growth Factor-1 and Insulin-like Growth Factor Binding Proteins from Differentiated Skeletal Muscle Cells

Stretch-induced skeletal muscle growth may involve increased autocrine secretion of insulin-like growth factor-1 (IGF-1) since IGF-1 is a potent growth factor for skeletal muscle hypertrophy, and stretch elevates IGF-1 mRNA levels in vivo. In tissue cultures of differentiated avian pectoralis skeletal muscle cells, nanomolar concentrations of exogenous IGF-1 stimulated growth in mechanically stretched but not static cultures. These cultures released up to 100 pg of endogenously produced IGF-1/micro-g of protein/day, as well as three major IGF binding proteins of 31, 36, and 43 kilodaltons (kDa). IGF-1 was secreted from both myofibers and fibroblasts coexisting in the muscle cultures. Repetitive stretch/relaxation of the differentiated skeletal muscle cells stimulated the acute release of IGF-1 during the first 4 h after initiating mechanical activity, but caused no increase in the long-term secretion over 24-72 h of IGF-1, or its binding proteins. Varying the intensity and frequency of stretch had no effect on the long-term efflux of IGF-1. In contrast to stretch, embedding the differentiated muscle cells in a three-dimensional collagen (Type I) matrix resulted in a 2-5-fold increase in long-term IGF-1 efflux over 24-72 h. Collagen also caused a 2-5-fold increase in the release of the IGF binding proteins. Thus, both the extracellular matrix protein type I collagen and stretch stimulate the autocrine secretion of IGF-1, but with different time kinetics. This endogenously produced growth factor may be important for the growth response of skeletal myofibers to both types of external stimuli

Galectin 1-A Key Player between Tissue Repair and Fibrosis

Galectins are ten family members of carbohydrate-binding proteins with a high affinity for β galactose-containing oligosaccharides. Galectin-1 (Gal-1) is the first protein discovered in the family, expressed in many sites under normal and pathological conditions. In the first part of the review article, we described recent advances in the Gal-1 modulatory role on wound healing, by focusing on the different phases triggered by Gal-1, such as inflammation, proliferation, tissue repair and re-epithelialization. On the contrary, Gal-1 persistent over-expression enhances angiogenesis and extracellular matrix (ECM) production via PI3K/Akt pathway activation and leads to keloid tissue. Therefore, the targeted Gal-1 modulation should be considered a method of choice to treat wound healing and avoid keloid formation. In the second part of the review article, we discuss studies clarifying the role of Gal-1 in the pathogenesis of proliferative diabetic retinopathy, liver, renal, pancreatic and pulmonary fibrosis. This evidence suggests that Gal-1 may become a biomarker for the diagnosis and prognosis of tissue fibrosis and a promising molecular target for the development of new and original therapeutic tools to treat fibrosis in different chronic diseases

Analysis of Coastal Areas Using SAR Images: A Case Study of the Dutch Wadden Sea Region

The increased availability of civil synthetic aperture radar (SAR) satellite images with different resolution allows us to compare the imaging capabilities of these instruments, to assess the quality of the available data and to investigate different areas (e.g., the Wadden Sea region). In our investigation, we propose to explore the content of TerraSAR-X and Sentinel-1A satellite images via a data mining approach in which the main steps are patch tiling, feature extraction, classification, semantic annotation and visual-statistical analytics. Once all the extracted categories are mapped and quantified, then the next step is to interpret them from an environmental point of view. The objective of our study is the application of semi-automated SAR image interpretation. Its novelty is the automated multiclass categorisation of coastal areas. We found out that the north-west of the Netherlands can be interpreted routinely as land surfaces by our satellite image analyses, while for the Wadden Sea, we can discriminate the different water levels and their impact on the visibility of the tidal flats. This necessitates a selection of time series data spanning a full tidal cycle

Refúgio e direito: as dificuldades da integração e de um recomeço no Brasil / Refugee and law: the difficults of the integration and a recommended in Brazil

O presente estudo trata sobre as dificuldades de reintegração dos refugiados no Brasil, analisando-se sob a ótica da educação como uma perspectiva de recomeço, visando responder o seguinte questionamento: há lacunas na legislação acerca do direito à educação de crianças e adolescentes refugiados? Para tanto foi utilizado o método de procedimento histórico-dedutivo, por meio da técnica de pesquisa indireta, a partir de um método de abordagem dedutivo. Para isso, observa-se a historicidade e conceituação acerca do refúgio, englobando pontos históricos imprescindíveis e complementando com dados e estatísticas onde verifica-se, especificamente, o número crescente e alarmante do que a ONU considera ser a pior crise humanitárias do século, além de tornar-se perceptível as possíveis consequências da ausência de legislação dessa específica e a importância da mesma

M1a prostate cancer:Results of a Dutch multidisciplinary consensus meeting

ObjectivesTo determine the consensus of a Dutch multidisciplinary expert panel on the diagnostic evaluation and treatment of de novo and recurrent metastatic prostate cancer (PCa) limited to non-regional lymph nodes (M1a) in daily clinical practice.Materials and methodsThe panel consisted of 37 Dutch specialists from disciplines involved in the management of M1a PCa (urology, medical and radiation oncology, radiology, and nuclear medicine). We used a modified Delphi method consisting of two voting rounds and a consensus meeting (video conference). Consensus (good agreement) was defined as the situation in which ≥ 75% of the panelists chose the same option.ResultsConsensus existed for 57% of the items. The panel agreed that prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) is the most appropriate standard imaging modality to identify de novo (100%) and recurrent (97%) M1a PCa. Androgen deprivation therapy (ADT) combined with radiotherapy to the prostate ± the M1a lesion(s) was most frequently considered an option for de novo M1a PCa. For M1a as recurrent disease, ADT alone, deferring treatment, or local radiotherapy to the M1a lesion(s) were judged to be the most important treatment options. However, no specific indications for treatment choice in relation to disease characteristics could be formulated.ConclusionsThe Dutch consensus panel preferred PSMA-PET/CT as the standard diagnostic modality to detect M1a PCa. Although potential treatment options were identified, explicit recommendations could not be formulated. This might (partly) be explained by the absence of high-level clinical evidence in this subset of patients. Further research is, therefore, strongly encouraged

Oligometastatic Prostate Cancer:Results of a Dutch Multidisciplinary Consensus Meeting

Background: Oligometastatic prostate cancer (OMPC) is a heterogeneous disease state that is imperfectly understood, and its clinical implications are unclear. Objective: To determine the consensus of a Dutch multidisciplinary expert panel on biological aspects, treatment goals, and management of OMPC in daily clinical practice. Design, setting, and participants: The study comprised a modified Delphi method including an explorative survey with various statements and questions, followed by a consensus meeting to discuss and determine the agreement with revised statements and related items. The panel consisted of 34 Dutch representatives from urology, medical and radiation oncology, radiology, nuclear medicine, and basic research. Outcome measurements and statistical analysis: Agreement was determined with statements (five-point scale). Consensus was defined as ≥75% panel agreement with a statement. Results and limitations: Consensus existed for 56% of statements. The panel agreed that OMPC comprises a limited metastatic spread in the hormone-sensitive setting, in both the synchronous and the metachronous presentation. Limited metastatic spread was believed to involve three to five metastases and a maximum of two organs. Prostate-specific membrane antigen positron emission tomography/computed tomography scan was currently perceived as the most accurate diagnostic imaging modality. Although there was a consensus that targeted treatment of all metastases in OMPC will delay further dissemination of the disease, opinions on specific treatment regimens were divided. Panel outcomes were limited by the lack of scientific evidence on OMPC. Conclusions: A multidisciplinary panel reached a consensus that OMPC is a specific disease state requiring a tailored treatment approach. OMPC registries and clinical studies should focus on both the biology and the clinical parameters in relation to optimal treatment strategies in synchronous and metachronous OMPC. Patient summary: A group of Dutch medical specialists agreed that prostate cancer patients having few metastases may benefit from a new therapeutic approach. Clinical studies need to determine which treatment is best for each specific situation. A multidisciplinary panel reached consensus that oligometastatic prostate cancer (OMPC) is a specific disease state requiring a tailored treatment approach. OMPC registries and clinical studies should provide insight into the biology and clinical parameters in relation to optimal treatment strategies in synchronous and metachronous OMPC

App’s como herramientas pedagógicas para el proceso de Enseñanza-Aprendizaje de la Física

In this paper some App’s that are free in the Play Store, are used in order to study uniformly accelerated movement, taking as examples the movement of a car on an inclined plane and the free fall of a smartphone. The graphs of position, velocity and acceleration as a function of time and the value of the acceleration of gravity are obtained, respectively. These applications are tools, easy to access and manipulate, which allow performing inexpensive experiments and articulate theory and practice in the teaching-learning processes of physics. The work was developed by students of the fourth semester of the Degree in Natural Sciences and Environmental Education - face-to-face modality - of the University of Tolima in the course of Fundamental Physics I - Mechanics.En este trabajo se usan algunas App´s gratuitas disponibles en Play Store, para estudiar Movimiento Uniformemente Acelerado, tomando como ejemplos   el movimiento de un carro sobre un plano inclinado y la caída libre de un Smartphone. Se obtuvieron las gráficas de posición, velocidad y aceleración en función del tiempo, y el valor de la aceleración de la gravedad, respectivamente. Estas aplicaciones son herramientas, de fácil acceso y manipulación, que permiten realizar experimentos de bajo costo y articular teoría y práctica en los procesos de enseñanza- aprendizaje de la física.  El trabajo fue desarrollado por estudiantes de cuarto semestre de la Licenciatura en Ciencias Naturales y Educación Ambiental- modalidad presencial – de la Universidad del Tolima en el curso de Física Fundamental I – Mecánica

Towards a Better Understanding of Genotype-Phenotype Correlations and Therapeutic Targets for Cardiocutaneous Genes:The Importance of Functional Studies above Prediction

Genetic variants in gene-encoding proteins involved in cell-cell connecting structures, such as desmosomes and gap junctions, may cause a skin and/or cardiac phenotype, of which the combination is called cardiocutaneous syndrome. The cardiac phenotype is characterized by cardiomyopathy and/or arrhythmias, while the skin particularly displays phenotypes such as keratoderma, hair abnormalities and skin fragility. The reported variants associated with cardiocutaneous syndrome, in genes DSP, JUP, DSC2, KLHL24, GJA1, are classified by interpretation guidelines from the American College of Medical Genetics and Genomics. The genotype-phenotype correlation, however, remains poorly understood. By providing an overview of variants that are assessed for a functional protein pathology, we show that this number (n = 115) is low compared to the number of variants that are assessed by in silico algorithms (>5000). As expected, there is a mismatch between the prediction of variant pathogenicity and the prediction of the functional effect compared to the real functional evidence. Aiding to improve genotype-phenotype correlations, we separate variants into 'protein reducing' or 'altered protein' variants and provide general conclusions about the skin and heart phenotype involved. We conclude by stipulating that adequate prognoses can only be given, and targeted therapies can only be designed, upon full knowledge of the protein pathology through functional investigation