211 research outputs found

    Hilft das zahnmedizinische Bonussystem den stationär Pflegebedürftigen?

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    Zusammenfassung: Die Mundgesundheit bei Pflegebedürftigen ist mangelhaft. Zufällig ausgewählte Pflegebedürftige (Berlin n=75, Nordrhein-Westfalen n=94, Sachsen n=73) aus 30 stationären Pflegeeinrichtungen wurden u.a. zu ihrem Verhalten der zahnmedizinischen Inanspruchnahme und der Nutzung ihres zahnmedizinischen Bonusheftes (zBH) befragt. Von 242Befragten (Median: 82Jahre, Range: 43-100Jahre, Frauen: 78,5%) besaßen nur 18,6% ein zBH, dabei gab es keine signifikanten geschlechts- und altersspezifischen Unterschiede. Regionale Unterschiede waren signifikant (Berlin 5,3%, Nordrhein-Westfalen 18,1%, Sachsen 32,9%; χ2-Test p<0,01). Die Zahnzahl war bei Bonusheftinhabern größer (Mann-Whitney-Test p=0,01), die Zeitspanne zum letzten Zahnarztbesuch geringer (p<0,01). Von den Bonusheftinhabern gaben 18,6% an, den Zahnarzt länger als 12Monate nicht aufgesucht zu haben (stationär Pflegebedürftige ohne Bonusheft 51,3%). Als Beitrag zur Qualitätssicherung, zur oralen Infektionskontrolle sowie zur Verbesserung der mundbezogenen und allgemeinen Lebensqualität wird die regelmäßige jährliche Durchführung zahnmedizinischer Reihenuntersuchungen mit dem Führen eines zBH für jeden Bewohner vorgeschlage

    Photothermal treatment of glioma; an in vitro study of macrophage-mediated delivery of gold nanoshells

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    One of the major factors that limits the treatment effectiveness for gliomas is the presence of the blood–brain barrier (BBB) which protects infiltrating glioma cells from the effects of anti-cancer agents. Circulating monocytes/macrophages (Ma) have a natural ability to traverse the intact and compromised BBB and loaded with anti cancer agents could be used as vectors to target tumors and surrounding tumor infiltrated tissue. Nanoshells (NS) are composed of a dielectric core (silica) coated with an ultrathin gold layer which converts absorbed near-infrared light (NIR) to heat with an extremely high efficacy and stability. We have investigated the effects of exposure to laser NIR on multicell human glioma spheroids infiltrated with empty (containing no nanoshells) or nanoshell loaded macrophages. Our results demonstrated that; (1) macrophages could efficiently take up bare or coated (PEGylated) gold NS: (2) NS loaded macrophages infiltrated into glioma spheroids to the same or, in some cases, to a greater degree than empty Ma; (3) NIR laser irradiation of spheroids incorporating NS loaded macrophages resulted in complete growth inhibition in an irradiance dependent manner, and (4) spheroids infiltrated with empty macrophages had growth curves identical to untreated control cultures. The results of this study provide proof of concept for the use of macrophages as a delivery vector of NS into gliomas for photothermal ablation and open the possibility of developing such regimens for patient treatment

    Comparative analysis of machine learning algorithms for multi-syndrome classification of neurodegenerative syndromes

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    Importance: The entry of artificial intelligence into medicine is pending. Several methods have been used for the predictions of structured neuroimaging data, yet nobody compared them in this context. Objective: Multi-class prediction is key for building computational aid systems for differential diagnosis. We compared support vector machine, random forest, gradient boosting, and deep feed-forward neural networks for the classification of different neurodegenerative syndromes based on structural magnetic resonance imaging. Design, setting, and participants: Atlas-based volumetry was performed on multi-centric T1-weighted MRI data from 940 subjects, i.e., 124 healthy controls and 816 patients with ten different neurodegenerative diseases, leading to a multi-diagnostic multi-class classification task with eleven different classes. Interventions: N.A. Main outcomes and measures: Cohen's kappa, accuracy, and F1-score to assess model performance. Results: Overall, the neural network produced both the best performance measures and the most robust results. The smaller classes however were better classified by either the ensemble learning methods or the support vector machine, while performance measures for small classes were comparatively low, as expected. Diseases with regionally specific and pronounced atrophy patterns were generally better classified than diseases with widespread and rather weak atrophy. Conclusions and relevance: Our study furthermore underlines the necessity of larger data sets but also calls for a careful consideration of different machine learning methods that can handle the type of data and the classification task best

    Glioblastoma multiforme with oligodendroglial component (GBMO): favorable outcome after post-operative radiotherapy and chemotherapy with nimustine (ACNU) and teniposide (VM26)

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    BACKGROUND: The presence of an oligodendroglial component within a glioblastoma multiforme (GBM) is considered a prognostically favorable factor, but the clinical outcome of patients with glioblastoma multiforme with oligodendroglial component (GBMO) after combined post-operative radiotherapy and chemotherapy has rarely been reported. METHODS: We analyzed overall and progression-free survival in a group of ten consecutive patients initially diagnosed with GBMO between 1996 and 2004 (4.2% of all GBM patients). Median (range) age was 54 (34–73) years, 90% were resected and median radiotherapy dose was 54 (45–60.6) Gy. 80% of patients received post-operative chemotherapy with nimustine (ACNU) and VM26 (teniposide) for a median of 3.5 (1–6) cycles, the remainder were treated with post-operative radiotherapy alone. All specimens were reviewed by an experienced neuropathologist. RESULTS: Neuropathological re-evaluation revealed GBM with an oligodendroglial component of 30% or less in five cases, predominant oligoastrocytic tumors with focal areas of GBM in four patients and WHO grade III oligoastrocytoma with questionable transition to GBM in one patient. Four of ten patients were alive at at 40, 41, 41 and 82 months. The median overall survival (Kaplan-Meier) was 26 months, the 2-year survival rate was 60% (progression-free survival: 9.8 months and 40%, respectively). CONCLUSION: In conclusion, patients with GBMO treated with post-operative radiotherapy and chemotherapy with ACNU/VM26 had a better prognosis than reported for GBM in modern chemoradiation series

    Propentofylline Targets TROY, a Novel Microglial Signaling Pathway

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    Glioblastoma multiforme (GBM) is the most common and aggressive primary brain cancer, with a median survival of less than 2 years after diagnosis with current available therapies. The tumor microenvironment serves a critical role in tumor invasion and progression, with microglia as a critical player. Our laboratory has previously demonstrated that propentofylline, an atypical methylxanthine with central nervous system glial modulating and anti-inflammatory actions, significantly decreases tumor growth in a GBM rodent model by preferentially targeting microglia. In the present study, we used the CNS-1 rat glioma model to elucidate the mechanisms of propentofylline. Here we demonstrate that propentofylline targets TROY, a novel signaling molecule up-regulated in infiltrating microglia, and not macrophages, in response to CNS-1 cells. We identify Pyk2, Rac1 and pJNK as the downstream signaling molecules of TROY through western blot analysis and siRNA transfection. We demonstrate that inhibition of TROY expression in microglia by siRNA transfection significantly inhibits microglial migration towards CNS-1 cells similar to 10 µM propentofylline treatment. These results identify TROY as a novel molecule expressed in microglia, involved in their migration and targeted by propentofylline. Furthermore, these results describe a signaling molecule that is differentially expressed between microglia and macrophages in the tumor microenvironment

    O ensino das ciências experimentais no liceu, em Portugal, na I República (1910-1926)

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    O ensino das ciências experimentais (ECE) em Portugal ficou, como pretendemos demonstrar, fortemente marcado pela instauração da República, que comemorou no ano transacto o seu centenário. A República de 1910 pretendeu reformar toda a mentalidade portuguesa, através do pilar base – a educação – pela qual seria capaz de sacudir a nossa maneira de ser, lançando desta forma o país para um progresso de nível europeu. O estudo a que nos propomos, uma investigação documental no domínio da História da Ciência1, visa aprofundar os conhecimentos existentes sobre esta época e perceber o impacto da reforma do ECE, principalmente nos Liceus, caracterizando as principais figuras, políticas e docentes responsáveis pela sua conceptualização e aplicação. Através desta investigação procuraremos lançar as primeiras bases para descobrir as origens deste pensamento, querendo ainda comparar os fundamentos psicopedagógicos, epistemológicos e sociológicos da época com as principais ideias actualmente presentes no ensino da Ciência. Com este trabalho pretendemos, num primeiro momento, apresentar e divulgar o desenho da investigação e os seus objectivos, na procura de estabelecer parcerias e receber contributos da comunidade académica interessada por esta problemática

    Dietary restriction reduces angiogenesis and growth in an orthotopic mouse brain tumour model

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    Diet and lifestyle produce major effects on tumour incidence, prevalence, and natural history. Moderate dietary restriction has long been recognised as a natural therapy that improves health, promotes longevity, and reduces both the incidence and growth of many tumour types. Dietary restriction differs from fasting or starvation by reducing total food and caloric intake without causing nutritional deficiencies. No prior studies have evaluated the responsiveness of malignant brain cancer to dietary restriction. We found that a moderate dietary restriction of 30–40% significantly inhibited the intracerebral growth of the CT-2A syngeneic malignant mouse astrocytoma by almost 80%. The total dietary intake for the ad libitum control group (n=9) and the dietary restriction experimental group (n=10) was about 20 and 13 Kcal day−1, respectively. Overall health and vitality was better in the dietary restriction-fed mice than in the ad libitum-fed mice. Tumour microvessel density (Factor VIII immunostaining) was two-fold less in the dietary restriction mice than in the ad libitum mice, whereas the tumour apoptotic index (TUNEL assay) was three-fold greater in the dietary restriction mice than in the ad libitum mice. CT-2A tumour cell-induced vascularity was also less in the dietary restriction mice than in the ad libitum mice in the in vivo Matrigel plug assay. These findings indicate that dietary restriction inhibited CT-2A growth by reducing angiogenesis and by enhancing apoptosis. Dietary restriction may shift the tumour microenvironment from a proangiogenic to an antiangiogenic state through multiple effects on the tumour cells and the tumour-associated host cells. Our data suggest that moderate dietary restriction may be an effective antiangiogenic therapy for recurrent malignant brain cancers

    In silico Experimentation of Glioma Microenvironment Development and Anti-tumor Therapy

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    Tumor cells do not develop in isolation, but co-evolve with stromal cells and tumor-associated immune cells in a tumor microenvironment mediated by an array of soluble factors, forming a complex intercellular signaling network. Herein, we report an unbiased, generic model to integrate prior biochemical data and the constructed brain tumor microenvironment in silico as characterized by an intercellular signaling network comprising 5 types of cells, 15 cytokines, and 69 signaling pathways. The results show that glioma develops through three distinct phases: pre-tumor, rapid expansion, and saturation. We designed a microglia depletion therapy and observed significant benefit for virtual patients treated at the early stages but strikingly no therapeutic efficacy at all when therapy was given at a slightly later stage. Cytokine combination therapy exhibits more focused and enhanced therapeutic response even when microglia depletion therapy already fails. It was further revealed that the optimal combination depends on the molecular profile of individual patients, suggesting the need for patient stratification and personalized treatment. These results, obtained solely by observing the in silico dynamics of the glioma microenvironment with no fitting to experimental/clinical data, reflect many characteristics of human glioma development and imply new venues for treating tumors via selective targeting of microenvironmental components

    Dynamic Predictive Modeling Under Measured and Unmeasured Continuous-Time Stochastic Input Behavior

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    Many input variables of chemical processes have a continuous-time stochastic (CTS) behavior. The nature of these variables is a persistent, time-correlated variation that manifests as process variation as the variables deviate in time from their nominal levels. This work introduces methodologies in process identification for improving the modeling of process outputs by exploiting CTS input modeling under cases where the input is measured and unmeasured. In the measured input case, the output variable is measured offline, infrequently, and at a varying sampling rate. A method is proposed for estimating CTS parameters from the measured input by exploiting statistical properties of its CTS model. The proposed approach is evaluated based on both output accuracy and predictive ability several steps ahead of the current input measurement. Two parameter estimation techniques are proposed when the input is unmeasured. The first is a derivative-free approach that uses sample moments and analytical expressions for population moments to estimate the CTS model parameters. The second exploits the CTS input model and uses the analytical solution of the dynamic model to estimate these parameters. The predictive ability of the latter approach is evaluated in the same way as the measured input case. All of the data in this work were artificially generated under the probabilistic CTS model.Reprinted (adapted) with permission from Industrial and Engineering Chemistry Research 51 (2012): 5469, doi: 10.1021/ie201998b. Copyright 2012 American Chemical Society.</p
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