26 research outputs found

    Solo living in the process of transitioning to adulthood in Europe: The role of socioeconomic background

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    Background: In recent decades, patterns of transition to adulthood have undergone substantial changes, including an increase in people living solo after leaving the parental home. However, the extent to which solo living after leaving the parental home is a transitory state, quickly followed by union formation, or a relatively long-term state in the pathways to adulthood, and how long-term solo living is socially stratified are all questions that remain unanswered. Objective: To fill this gap, this study focuses on home-leaving pathways that have unfolded over a 5-year period after leaving home. It explores the association between socioeconomic background (parental education) and the long-term, solo-living, home-leaving pathways of young men and women across 29 European countries. Methods: Using European Social Survey Round 9 (2018) data, this study applies a competing trajectory analysis, which combines sequence analysis to identify home-leaving patterns with event history analysis, in order to analyse their association with parental education. Results: The occurrence of solo-living pathways varies considerably across Europe: both short-term and long-term solo-living pathways are the highest in Northern Europe. Long-term solo-living pathways are associated with being in education and with high levels of individual and parental education. The effect of parental education does not differ systematically across European countries and does not differ between genders. Contribution: This study contributes to the understanding of the social stratification of the transition to adulthood across European countries by differentiating between transitory and longer-term solo-living, home-leaving pathways

    Serum neurofilament light in familial Alzheimer disease: A marker of early neurodegeneration.

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    OBJECTIVES: To investigate whether serum neurofilament light (NfL) concentration is increased in familial Alzheimer disease (FAD), both pre and post symptom onset, and whether it is associated with markers of disease stage and severity. METHODS: We recruited 48 individuals from families with PSEN1 or APP mutations to a cross-sectional study: 18 had symptomatic Alzheimer disease (AD) and 30 were asymptomatic but at 50% risk of carrying a mutation. Serum NfL was measured using an ultrasensitive immunoassay on the single molecule array (Simoa) platform. Cognitive testing and MRI were performed; 33 participants had serial MRI, allowing calculation of atrophy rates. Genetic testing established mutation status. A generalized least squares regression model was used to compare serum NfL among symptomatic mutation carriers, presymptomatic carriers, and noncarriers, adjusting for age and sex. Spearman coefficients assessed associations between serum NfL and (1) estimated years to/from symptom onset (EYO), (2) cognitive measures, and (3) MRI measures of atrophy. RESULTS: Nineteen of the asymptomatic participants were mutation carriers (mean EYO -9.6); 11 were noncarriers. Compared with noncarriers, serum NfL concentration was higher in both symptomatic (p < 0.0001) and presymptomatic mutation carriers (p = 0.007). Across all mutation carriers, serum NfL correlated with EYO (ρ = 0.81, p < 0.0001) and multiple cognitive and imaging measures, including Mini-Mental State Examination (ρ = -0.62, p = 0.0001), Clinical Dementia Rating Scale sum of boxes (ρ = 0.79, p < 0.0001), baseline brain volume (ρ = -0.62, p = 0.0002), and whole-brain atrophy rate (ρ = 0.53, p = 0.01). CONCLUSIONS: Serum NfL concentration is increased in FAD prior to symptom onset and correlates with measures of disease stage and severity. Serum NfL may thus be a feasible biomarker of early AD-related neurodegeneration

    Исследование качества фосфатных минеральных удобрений

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    Дипломная работа посвящена анализу состава и свойств фосфатных минеральных удобрений. При выполнении данной работы в качестве образца фосфатного минерального удобрения был выбран монокальцийфосфат. В качестве основных анализируемых показателей качества в работе были выбраны следующие показатели: содержание кальция, содержание фосфора, содержание воды, рН, содержание мышьяка. Определение выбранных показателей проводилось методами, рекомендованными нормативными документами на исследуемую продукцию, а также, физико-химическими методами анализа в качестве методов сравнения. Данная дипломная работа состоит из введения, литературного обзора, характеристики монокальцийфосфата, методов анализа монокальцийфосфата, экспериментальной части, обсуждения результатов, списка литературы.The thesis is devoted to the analysis of the composition and properties of phosphate fertilizers. When performing this work as a sample of phosphate fertilizers was chosen as monocalcium phosphate. As the main analyzed indicators of quality in work were chosen the following indicators: calcium content, phosphorus content, water content, pH, arsenic. The definition of the selected indicators was carried out by methods recommended by the regulatory documents on investigational products, as well as, physico-chemical analysis methods as methods of comparison. This thesis consists of an introduction, literature review, characteristics of monocalcium phosphate, methods of analysis of monocalcium phosphate, experimental part, discussion of results, references

    Impact of a 12-week olfactory training programme in women with migraine with aura: protocol for a double-blind, randomised, placebo-controlled trial

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    Introduction Migraine is a leading cause of disability and suffering worldwide. However, conventional pharmacological migraine preventive therapies are often challenging and accompanied by adverse effects. Recently, structured odour exposure has shown to successfully increase pain thresholds in patients with chronic back pain. Despite the importance of the olfactory system in migraine, there are no studies investigating the impact of structured odour exposure in patients with migraine.Methods and analysis This double-blind randomised placebo-controlled trial will be conducted at the Headache Clinic of the University Pain Center at TU Dresden, Germany and aims at investigating the impact of a 12-week structured exposure to odours in women with migraine. Fifty-four women between 18 and 55 years with migraine with aura will be recruited and randomised to training with odours and odourless training. The primary outcomes are mechanical and electrical pain thresholds. Secondary outcomes comprise olfactory threshold and the number of headache days. Other exploratory measurements are headache associated pain intensity, acute analgesic intake, symptoms of anxiety and depression, and quality of life. Additionally, this protocol assesses neuroanatomical and neurofunctional changes associated with the 12-week olfactory training. Data analysis will be executed on the basis of the general linear model considering repeated measurements.Ethics and dissemination Ethical approvals were obtained from the Ethics Board of the TU Dresden (Protocol No. BO-EK-353082020). Participation will only be possible after written informed consent is provided. Findings will be disseminated through peer-reviewed journals and scientific conferences.Trial registration number DRKS00027399

    Suicide-Gene-Modified Extracellular Vesicles of Human Primary Uveal Melanoma in Future Therapies

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    Extracellular vesicles secreted from uveal melanoma (UM) cells are involved in the establishment of the premetastatic niche and display transforming potential for the formation of metastases, preferentially in the liver. In this study, we cultivated human primary UM cells and uveal melanoma-associated fibroblasts in vitro to be transduced by infection with a retrovirus containing the suicide gene—fused yeast cytosine deaminase::uracil phospho-ribosyl transferase (yCD::UPRT). A homogenous population of yCD::UPRT-UM cells with the integrated provirus expressed the gene, and we found it to continuously secrete small extracellular vesicles (sEVs) possessing mRNA of the suicide gene. The yCD::UPRT-UM-sEVs were internalized by tumor cells to the intracellular conversion of the prodrug 5-fluorocytosine (5-FC) to the cytotoxic drug 5-fluorouracil (5-FU). The host range of the yCD::UPRT-UM-sEVs was not limited to UMs only. The yCD::UPRT-UM-sEVs inhibited the growth of the human cutaneous melanoma cell line A375 and uveal melanoma cell line MP38, as well as other primary UMs, to various extents in vitro. The yCD::UPRT-UM-sEVs hold the therapeutic and prophylactic potential to become a therapeutic drug for UM. However, the use of yCD::UPRT-UM-sEVs must first be tested in animal preclinical studies

    Bordetella Adenylate Cyclase Toxin Elicits Airway Mucin Secretion through Activation of the cAMP Response Element Binding Protein

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    The mucus layer protects airway epithelia from damage by noxious agents. Intriguingly, Bordetella pertussis bacteria provoke massive mucus production by nasopharyngeal epithelia during the initial coryza-like catarrhal stage of human pertussis and the pathogen transmits in mucus-containing aerosol droplets expelled by sneezing and post-nasal drip-triggered cough. We investigated the role of the cAMP-elevating adenylate cyclase (CyaA) and pertussis (PT) toxins in the upregulation of mucin production in B. pertussis-infected airway epithelia. Using human pseudostratified airway epithelial cell layers cultured at air–liquid interface (ALI), we show that purified CyaA and PT toxins (100 ng/mL) can trigger production of the major airway mucins Muc5AC and Muc5B. Upregulation of mucin secretion involved activation of the cAMP response element binding protein (CREB) and was blocked by the 666-15-Calbiochem inhibitor of CREB-mediated gene transcription. Intriguingly, a B. pertussis mutant strain secreting only active PT and producing the enzymatically inactive CyaA-AC– toxoid failed to trigger any important mucus production in infected epithelial cell layers in vitro or in vivo in the tracheal epithelia of intranasally infected mice. In contrast, the PT– toxoid-producing B. pertussis mutant secreting the active CyaA toxin elicited a comparable mucin production as infection of epithelial cell layers or tracheal epithelia of infected mice by the wild-type B. pertussis secreting both PT and CyaA toxins. Hence, the cAMP-elevating activity of B. pertussis-secreted CyaA was alone sufficient for activation of mucin production through a CREB-dependent mechanism in B. pertussis-infected airway epithelia in vivo

    Supplementary Material for: Molecular Cytogenetic Diagnostics of Marker Chromosomes: Analysis in Four Prenatal Cases and Long-Term Clinical Evaluation of Carriers

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    he prenatal finding of a small supernumerary marker chromosome (sSMC) is a challenge for genetic counseling. Our analytic algorithm is based on sSMC frequencies and multicolor FISH to accelerate the procedure. The chromosomal origin, size, and degree of mosaicism of the sSMC then determine the prognosis. We illustrate the effectiveness on 4 prenatally identified de novo mosaic sSMCs derived from chromosomes 13/21, X, 3, and 17. Three sSMC carriers had a good prognosis and apparently healthy children were born, showing no abnormality till the last examination at the age of 4 years. One case had a poor prognosis, and the parents decided to terminate the pregnancy. Our work contributes to the laboratory and clinical management of prenatally detected sSMCs. FISH is a reliable method for fast sSMC evaluation and prognosis assessment; it prevents unnecessary delays and uncertainty, allows informed decision making, and reduces unnecessary pregnancy terminations. <br

    The Gene Regulatory Network of Lens Induction Is Wired through Meis-Dependent Shadow Enhancers of <i>Pax6</i>

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    <div><p>Lens induction is a classical developmental model allowing investigation of cell specification, spatiotemporal control of gene expression, as well as how transcription factors are integrated into highly complex gene regulatory networks (GRNs). <i>Pax6</i> represents a key node in the gene regulatory network governing mammalian lens induction. Meis1 and Meis2 homeoproteins are considered as essential upstream regulators of <i>Pax6</i> during lens morphogenesis based on their interaction with the ectoderm enhancer (EE) located upstream of <i>Pax6</i> transcription start site. Despite this generally accepted regulatory pathway, Meis1-, Meis2- and EE-deficient mice have surprisingly mild eye phenotypes at placodal stage of lens development. Here, we show that simultaneous deletion of <i>Meis1</i> and <i>Meis2</i> in presumptive lens ectoderm results in arrested lens development in the pre-placodal stage, and neither lens placode nor lens is formed. We found that in the presumptive lens ectoderm of Meis1/Meis2 deficient embryos Pax6 expression is absent. We demonstrate using chromatin immunoprecipitation (ChIP) that in addition to EE, Meis homeoproteins bind to a remote, ultraconserved SIMO enhancer of <i>Pax6</i>. We further show, using <i>in vivo</i> gene reporter analyses, that the lens-specific activity of SIMO enhancer is dependent on the presence of three Meis binding sites, phylogenetically conserved from man to zebrafish. Genetic ablation of EE and SIMO enhancers demostrates their requirement for lens induction and uncovers an apparent redundancy at early stages of lens development. These findings identify a genetic requirement for Meis1 and Meis2 during the early steps of mammalian eye development. Moreover, they reveal an apparent robustness in the gene regulatory mechanism whereby two independent "shadow enhancers" maintain critical levels of a dosage-sensitive gene, <i>Pax6</i>, during lens induction.</p></div
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