Hoitotyön ammattiosaaminen ja kehittäminen ikääntyneiden mielenterveys- ja päihdetyössä tehostetussa palveluasumisessa

Saharinen, Saija & Urpilainen, Viivi. Hoitotyön ammattiosaaminen ja kehittäminen ikääntyneiden mielenterveys- ja päihdetyössä tehostetussa palveluasumisessa. Pieksämäki, kevät 2015, 73 sivua, 3 liitettä. Diakonia-ammattikorkeakoulu, Pieksämäen toi-mipiste. Terveysalan koulutusohjelma, sairaanhoitaja (AMK). Opinnäytetyön tarkoitus oli selvittää millainen on hoitotyön ammattilaisten ammattiosaaminen ja lisätiedon tarve ikääntyneiden mielenterveys- ja päihdeasiakkaiden hoitotyöstä. Tutkimuksen tavoitteena oli selvittää hoitotyön ammattilaisten ammattiosaa-misten vahvuudet ja laatia ehdotus lisäkoulutuksesta liittyen ikääntyneiden mielenterveys- ja päihdeasiakkaiden hoitotyöhön. Tutkimuksemme toimeksiantajana toimivat Jyväskylän kaupungin vanhus- ja vammaispalvelujen Kyllikinkadun palvelukeskus ja yhteistyötahona Jyväskylän kaupungin varahenkilöyksikkö. Käytimme tutkimuksessamme kahta tutkimusmenetelmää: kvantitatiivista eli määrällistä ja kvalitatiivista eli laadullista. Tutkimusaineisto kerättiin kyselylomakkeella, joka sisälsi strukturoituja kysymyksiä sekä avoimia kysymyksiä. Kyselyyn vastasi 57 hoitotyön am-mattilaista. Tutkimustuloksissa ilmeni, että hoitotyön ammattilaisten ammattiosaamisen vahvuudet oli tunnistaa ikääntyneiden yleisimpiä mielenterveysongelmien oireita, lääke- ja alkoholiriippuvuuksia sekä kuntouttavan työotteen ja asiakkaan sosiaalisten suhteiden luomisen ja ylläpitämisen menetelmiä. Tutkimustulokset osoittivat, että ikääntyneiden mielenterveys- ja päihdeasiakkaiden hoitotyössä lisäkoulutusta tarvitaan lääkehoidon eettiseen ja lainsäädännölliseen toteuttamiseen, psyykenlääkkeiden haitta- ja sivuvaikutuksiin, väkivaltatilanteiden ennaltaehkäisyyn sekä mittarit ja kyselyt toimintakyvyn tunnistamisen apuvälineisiin. Avainsanat: Ikääntynyt, mielenterveysongelma, päihde, ammattiosaaminenSaharinen, Saija & Urpilainen, Viivi. The professional skills and the development of the care work for the elderly mental health and substance abuse patients in an intensified supported housing. Spring 2015, 73 pages, 3 attachments. Diaconia University of Applied Sciences, Pieksämäki. Degree Program in Health Care. Degree: Bachelor of Health Care. The aim of this thesis was to examine the quality of the professional skills among nursing professionals and the need for further education for the nursing professionals taking care of the elderly mental health and substance abuse patients. The goal of this study was to discover the strengths of the care work by the current health care personnel and prepare a proposal for further education for the nursing professionals of elderly mental health and substance abuse patients The study was conducted in cooperation with both the units of elderly and disabled services and the deputy unit of the City of Jyväskylä. In our study, we used two research methods: quantitative and qualitative. The research data was collected by using a questionnaire containing structured questions and open-ended questions. We received responses from 57 nursing professionals. The survey revealed that the strengths of the current health care personnel were the skills to identify the most common symptoms of the elderly with mental health problems and drug and alcohol addictions as well as to identify the approaches used in rehabilitation as well as in building and maintenance of the social relationships of the elderly patients. Based on the results, further education and more knowledge is needed on the ethical and legislative execution of medicinal care, the adverse side effects of psychotic drugs, and in the prevention and recognition of violent behavior as well as on the use of measuring devices and questionnaires as tools to recognize and analyze the performance skills of the elderly mental health and substance abuse patients. Key words: elderly, mental health problems, substance abuse, professional skill

Lymphatic endothelium stimulates melanoma metastasis and invasion via MMP14-dependent Notch3 and b1-integrin activation

Lymphatic invasion and lymph node metastasis correlate with poor clinical outcome in melanoma. However, the mechanisms of lymphatic dissemination in distant metastasis remain incompletely understood. We show here that exposure of expansively growing human WM852 melanoma cells, but not singly invasive Bowes cells, to lymphatic endothelial cells (LEC) in 3D co-culture facilitates melanoma distant organ metastasis in mice. To dissect the underlying molecular mechanisms, we established LEC co-cultures with different melanoma cells originating from primary tumors or metastases. Notably, the expansively growing metastatic melanoma cells adopted an invasively sprouting phenotype in 3D matrix that was dependent on MMP14, Notch3 and β1-integrin. Unexpectedly, MMP14 was necessary for LEC-induced Notch3 induction and coincident β1-integrin activation. Moreover, MMP14 and Notch3 were required for LEC-mediated metastasis of zebrafish xenografts. This study uncovers a unique mechanism whereby LEC contact promotes melanoma metastasis by inducing a reversible switch from 3D growth to invasively sprouting cell phenotype

Brain gene expression profiles of and deficient mice unravels common molecular pathways underlying neuronal degeneration in NCL diseases

BackgroundThe neuronal ceroid lipofuscinoses (NCL) are a group of children's inherited neurodegenerative disorders, characterized by blindness, early dementia and pronounced cortical atrophy. The similar pathological and clinical profiles of the different forms of NCL suggest that common disease mechanisms may be involved. To explore the NCL-associated disease pathology and molecular pathways, we have previously produced targeted knock-out mice for Cln1 and Cln5. Both mouse-models replicate the NCL phenotype and neuropathology; the Cln1-/- model presents with early onset, severe neurodegenerative disease, whereas the Cln5-/- model produces a milder disease with a later onset.ResultsHere we have performed quantitative gene expression profiling of the cortex from 1 and 4 month old Cln1-/- and Cln5-/- mice. Combined microarray datasets from both mouse models exposed a common affected pathway: genes regulating neuronal growth cone stabilization display similar aberrations in both models. We analyzed locus specific gene expression and showed regional clustering of Cln1 and three major genes of this pathway, further supporting a close functional relationship between the corresponding gene products; adenylate cyclase-associated protein 1 (Cap1), protein tyrosine phosphatase receptor type F (Ptprf) and protein tyrosine phosphatase 4a2 (Ptp4a2). The evidence from the gene expression data, indicating changes in the growth cone assembly, was substantiated by the immunofluorescence staining patterns of Cln1-/- and Cln5-/- cortical neurons. These primary neurons displayed abnormalities in cytoskeleton-associated proteins actin and beta-tubulin as well as abnormal intracellular distribution of growth cone associated proteins GAP-43, synapsin and Rab3.ConclusionOur data provide the first evidence for a common molecular pathogenesis behind neuronal degeneration in INCL and vLINCL. Since CLN1 and CLN5 code for proteins with distinct functional roles these data may have implications for other forms of NCLs as well

The complex TIE between macrophages and angiogenesis

Macrophages are primarily known as phagocytic immune cells, but they also play a role in diverse processes, such as morphogenesis, homeostasis and regeneration. In this review, we discuss the influence of macrophages on angiogenesis, the process of new blood vessel formation from the pre-existing vasculature. Macrophages play crucial roles at each step of the angiogenic cascade, starting from new blood vessel sprouting to the remodelling of the vascular plexus and vessel maturation. Macrophages form promising targets for both pro- and anti-angiogenic treatments. However, to target macrophages, we will first need to understand the mechanisms that control the functional plasticity of macrophages during each of the steps of the angiogenic cascade. Here, we review recent insights in this topic. Special attention will be given to the TIE2-expressing macrophage (TEM), which is a subtype of highly angiogenic macrophages that is able to influence angiogenesis via the angiopoietin-TIE pathway

Endothelial Wnt/β-catenin signaling inhibits glioma angiogenesis and normalizes tumor blood vessels by inducing PDGF-B expression

Endothelial Wnt/β-catenin signaling is necessary for angiogenesis of the central nervous system and blood–brain barrier (BBB) differentiation, but its relevance for glioma vascularization is unknown. In this study, we show that doxycycline-dependent Wnt1 expression in subcutaneous and intracranial mouse glioma models induced endothelial Wnt/β-catenin signaling and led to diminished tumor growth, reduced vascular density, and normalized vessels with increased mural cell attachment. These findings were corroborated in GL261 glioma cells intracranially transplanted in mice expressing dominant-active β-catenin specifically in the endothelium. Enforced endothelial β-catenin signaling restored BBB characteristics, whereas inhibition by Dkk1 (Dickkopf-1) had opposing effects. By overactivating the Wnt pathway, we induced the Wnt/β-catenin–Dll4/Notch signaling cascade in tumor endothelia, blocking an angiogenic and favoring a quiescent vascular phenotype, indicated by induction of stalk cell genes. We show that β-catenin transcriptional activity directly regulated endothelial expression of platelet-derived growth factor B (PDGF-B), leading to mural cell recruitment thereby contributing to vascular quiescence and barrier function. We propose that reinforced Wnt/β-catenin signaling leads to inhibition of angiogenesis with normalized and less permeable vessels, which might prove to be a valuable therapeutic target for antiangiogenic and edema glioma therapy

Analysis of jak2 catalytic function by peptide microarrays: The role of the JH2 domain and V617F mutation

Janus kinase 2 (JAK2) initiates signaling from several cytokine receptors and is required for biological responses such as erythropoiesis. JAK2 activity is controlled by regulatory proteins such as Suppressor of Cytokine Signaling (SOCS) proteins and protein tyrosine phosphatases. JAK2 activity is also intrinsically controlled by regulatory domains, where the pseudokinase (JAK homology 2, JH2) domain has been shown to play an essential role. The physiological role of the JH2 domain in the regulation of JAK2 activity was highlighted by the discovery of the acquired missense point mutation V617F in myeloproliferative neoplasms (MPN). Hence, determining the precise role of this domain is critical for understanding disease pathogenesis and design of new treatment modalities. Here, we have evaluated the effect of inter-domain interactions in kinase activity and substrate specificity. By using for the first time purified recombinant JAK2 proteins and a novel peptide micro-array platform, we have determined initial phosphorylation rates and peptide substrate preference for the recombinant kinase domain (JH1) of JAK2, and two constructs comprising both the kinase and pseudokinase domains (JH1-JH2) of JAK2. The data demonstrate that (i) JH2 drastically decreases the activity of the JAK2 JH1 domain, (ii) JH2 increased the Kmfor ATP (iii) JH2 modulates the peptide preference of JAK2 (iv) the V617F mutation partially releases this inhibitory mechanism but does not significantly affect substrate preference or Kmfor ATP. These results provide the biochemical basis for understanding the interaction between the kinase and the pseudokinase domain of JAK2 and identify a novel regulatory role for the JAK2 pseudokinase domain. Additionally, this method can be used to identify new regulatory mechanisms for protein kinases that provide a better platform for designing specific strategies for therapeutic approaches

Biological, clinical and population relevance of 95 loci for blood lipids.

Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD