Tuki, osallisuus ja yhteistoiminta lasten ja perheiden palveluissa - Työntekijöiden näkökulma

Lapsiperheiden palvelujen johtaminen kokonaisuutena kuntien nykyisissä ja uudistuvissakin kunta- sekä sosiaali- ja terveydenhuollon palvelurakenteissa on haastavaa. Johtajien ja työntekijöiden osaaminen ja toiminta ovat edellytyksiä vaikuttaville ja laadukkaille lasten ja perheiden palveluille. Päätöksentekoa ja kehittämistä tukee tieto lasten ja perheiden terveydestä ja tuen tarpeesta sekä heidän käyttämistään palveluista ja siitä, miten ne vastaavat tarpeisiin. Tietoa tarvitaan myös palvelujen saatavuudesta ja järjestämisestä. Tässä raportissa arvioidaan lasten ja perheiden palveluja kokonaisuutena. Arvioijina ovat äitiys- ja lastenneuvolan, kouluterveydenhuollon, päivähoidon, esi- ja perusopetuksen työntekijät. Kiinnostuksen kohteina ovat lapsiperheiden tuen tarpeet ja avun antaminen, palvelujen riittävyys, kehittämistarpeet, vanhempien osallisuus, päätöksenteko ja yhteistoiminta lapsiperheiden ja muiden tahojen kanssa. Raportti on tarkoitettu kaikille lasten ja perheiden parissa toimiville; työntekijöille, johtajille ja kehittäjille sekä alan opiskelijoille ja opettajille

Inhibition of receptor tyrosine kinase signalling by small molecule agonist of T-cell protein tyrosine phosphatase

<p>Abstract</p> <p>Background</p> <p>T-cell protein tyrosine phosphatase (TCPTP/TC45) is a ubiquitously expressed intra-cellular non-receptor protein tyrosine phosphatase involved in the negative regulation of several cancer relevant cellular signalling pathways. We have previously shown that interaction between the α-cytoplasmic tail of α1β1 integrin and TCPTP activates TCPTP by disrupting an inhibitory intra-molecular bond in TCPTP. Thus, inhibition of the regulatory interaction in TCPTP is a desirable strategy for TCPTP activation and attenuation of oncogenic RTK signalling. However, this is challenging with low molecular weight compounds.</p> <p>Methods</p> <p>We developed a high-throughput compatible assay to analyse activity of recombinant TCPTP in vitro. Using this assay we have screened 64280 small molecules to identify novel agonists for TCPTP. Dose-dependent response to TCPTP agonist was performed using the in vitro assay. Inhibition effects and specificity of TCPTP agonists were evaluated using TCPTP expressing and null mouse embryonic fibroblasts. Western blot analysis was used to evaluate attenuation of PDGFRβ and EGFR phosphorylation. Inhibition of VEGF signalling was analysed with VEGF-induced endothelial cell sprouting assays.</p> <p>Results</p> <p>From the screen we identified six TCPTP agonists. Two compounds competed with α1-cytoplasmic domain for binding to TCPTP, suggesting that they activate TCPTP similar to α1-cyt by disrupting the intra-molecular bond in TCPTP. Importantly, one of the compounds (spermidine) displayed specificity towards TCPTP in cells, since TCPTP -/- cells were 43-fold more resistant to the compound than TCPTP expressing cells. This compound attenuates PDGFRβ and VEGFR2 signalling in cells in a TCPTP-dependent manner and functions as a negative regulator of EGFR phosphorylation in cancer cells.</p> <p>Conclusions</p> <p>In this study we showed that small molecules mimicking TCPTP-α1 interaction can be used as TCPTP agonists. These data provide the first proof-of-concept description of the use of high-throughput screening to identify small molecule PTP activators that could function as RTK antagonists in cells.</p

Identification of MicroRNAs Inhibiting TGF-beta-Induced IL-11 Production in Bone Metastatic Breast Cancer Cells

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Marine Microalgae: Promising Source for New Bioactive Compounds

The study of marine natural products for their bioactive potential has gained strength in recent years. Oceans harbor a vast variety of organisms that offer a biological and chemical diversity with metabolic abilities unrivalled in terrestrial systems, which makes them an attractive target for bioprospecting as an almost untapped resource of biotechnological applications. Among them, there is no doubt that microalgae could become genuine cell factories for the biological synthesis of bioactive substances. Thus, in the course of inter-laboratory collaboration sponsored by the European Union (7th FP) into the MAREX Project focused on the discovery of novel bioactive compounds of marine origin for the European industry, a bioprospecting study on 33 microalgae strains was carried out. The strains were cultured at laboratory scale. Two extracts were prepared for each one (biomass and cell free culture medium) and, thus, screened to provide information on the antimicrobial, the anti-proliferative, and the apoptotic potential of the studied extracts. The outcome of this study provides additional scientific data for the selection of Alexandrium tamarensis WE, Gambierdiscus australes, Prorocentrum arenarium, Prorocentrum hoffmannianum, and Prorocentrum reticulatum (Pr-3) for further investigation and offers support for the continued research of new potential drugs for human therapeutics from cultured microalgae.Peer reviewe

ASIC-E4: Interplay of Beta-Amyloid, Synaptic Density and Neuroinflammation in Cognitively Normal Volunteers With Three Levels of Genetic Risk for Late-Onset Alzheimer's Disease - Study Protocol and Baseline Characteristics

Background:& nbsp;Detailed characterization of early pathophysiological changes in preclinical Alzheimer's disease (AD) is necessary to enable development of correctly targeted and timed disease-modifying treatments. ASIC-E4 study ( "Beta-Amyloid, Synaptic loss, Inflammation and Cognition in healthy APOE epsilon 4 carriers ") combines state-of-the-art neuroimaging and fluid-based biomarker measurements to study the early interplay of three key pathological features of AD, i.e., beta-amyloid (A beta) deposition, neuroinflammation and synaptic dysfunction and loss in cognitively normal volunteers with three different levels of genetic (APOE-related) risk for late-onset AD.& nbsp;Objective:& nbsp;Here, our objective is to describe the study design, used protocols and baseline demographics of the ASIC-E4 study.& nbsp;Methods/Design:& nbsp;ASIC-E4 is a prospective observational multimodal imaging study performed in Turku PET Centre in collaboration with University of Gothenburg. Cognitively normal 60-75-year-old-individuals with known APOE epsilon 4/epsilon 4 genotype were recruited via local Auria Biobank (Turku, Finland). Recruitment of the project has been completed in July 2020 and 63 individuals were enrolled to three study groups (Group 1: APOE epsilon 4/epsilon 4, N = 19; Group 2: APOE epsilon 4/epsilon 3, N = 22; Group 3: APOE epsilon 3/epsilon 3, N = 22). At baseline, all participants will undergo positron emission tomography imaging with tracers targeted against A beta deposition (C-11-PIB), activated glia (C-11-PK11195) and synaptic vesicle glycoprotein 2A (C-11-UCB-J), two brain magnetic resonance imaging scans, and extensive cognitive testing. In addition, blood samples are collected for various laboratory measurements and blood biomarker analysis and cerebrospinal fluid samples are collected from a subset of participants based on additional voluntary informed consent. To evaluate the predictive value of the early neuroimaging findings, neuropsychological evaluation and blood biomarker measurements will be repeated after a 4-year follow-up period.& nbsp;Discussion:& nbsp;Results of the ASIC-E4 project will bridge the gap related to limited knowledge of the synaptic and inflammatory changes and their association with each other and A beta in "at-risk " individuals. Thorough in vivo characterization of the biomarker profiles in this population will produce valuable information for diagnostic purposes and future drug development, where the field has already started to look beyond A beta

Proyecto de pre factibilidad para la implementación de una planta de concreto seco premezclado

El presente estudio tiene como objetivo fundamental evaluar la factibilidad de implementar una planta de concreto seco premezclado, la cual surge a partir de ofrecer una propuesta ideal e integral, ante todo práctica y sencilla, un producto alternativo a lo ya existente, está dirigido para todas aquellas personas que requieran edificar, ampliar o remodelar sus viviendas. En el capítulo inicial se efectuaron estudios en donde se determinaron los antecedentes relacionados con el proyecto así como también fundamentos teóricos importantes para el respaldo conceptual del desarrollo del proyecto. El desarrollo del estudio y análisis del mercado se determinó que existe demanda potencial con relación a la oferta existente. Además se analizó la competencia y se plantearon las estrategias de comercialización que deben realizarse para la introducción del producto. En cuanto al estudio técnico (ingeniería del proyecto), se determinó el tamaño, ubicación, infraestructura, distribución de las áreas y espacios a través de métodos como Guerchet, factores ponderados, análisis de proximidad entre aéreas, así como también procesos de generación del producto a través de los diagramas de flujo , operaciones y análisis de procesos , asimismo requerimiento de materiales , personal , entre otros. Por último la inversión que necesita el proyecto, se especifica en el capítulo estudio financiero, detallados en los estados financieros como: estado de resultados, flujo caja; éste último sirviendo de base para la evaluación financiera correspondiente; asimismo el punto de equilibrio y el análisis de sensibilidad, estudio que permite determinar si el proyecto es viable y rentable en el tiempo

Planetary well-being

Tensions between the well-being of present humans, future humans, and nonhuman nature manifest in social protests and political and academic debates over the future of Earth. The increasing consumption of natural resources no longer increases, let alone equalises, human well-being, but has led to the current ecological crisis and harms both human and nonhuman well-being. While the crisis has been acknowledged, the existing conceptual frameworks are in some respects ill-equipped to address the crisis in a way that would link the resolving of the crisis with the pivotal aim of promoting equal well-being. The shortcomings of the existing concepts in this respect relate to anthropocentric normative orientation, methodological individualism that disregards process dynamics and precludes integrating the considerations of human and nonhuman well-being, and the lack of multiscalar considerations of well-being. This work derives and proposes the concept of planetary well-being to address the aforementioned conceptual issues, to recognise the moral considerability of both human and nonhuman well-being, and to promote transdisciplinary, cross-cultural discourse for addressing the crisis and for promoting societal and cultural transformation. Conceptually, planetary well-being shifts focus on well-being from individuals to processes, Earth system and ecosystem processes, that underlie all well-being. Planetary well-being is a state where the integrity of Earth system and ecosystem processes remains unimpaired to a degree that species and populations can persist to the future and organisms have the opportunity to achieve well-being. After grounding and introducing planetary well-being, this work shortly discusses how the concept can be operationalised and reflects upon its potential as a bridging concept between different worldviews.</p

High-Throughput 3D Screening Reveals Differences in Drug Sensitivities between Culture Models of JIMT1 Breast Cancer Cells

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