Krooninen väsymysoireyhtymä : Etiologia, diagnostiikka, hoito sekä kuntoutusinterventiot

Tämän kroonisen väsymysoireyhtymän (KVO) diagnostiikkaa, etiologiaa ja hoitokeinojen vaikuttavuutta koskevan selvityksen menetelminä ovat systemaattinen kirjallisuuskatsaus ja kysely. Aiheen laajuuden vuoksi liikkeelle lähdettiin julkaistuista systemaattisista kirjallisuuskatsauksista, ja näistä saatavaa tietoa täydennettiin uusilla alkuperäistutkimuksilla. Katsausten ja hoitotutkimusten laatu arvioitiin ja näytönaste arvioitiin lopputulosmuuttujittain. Suomen hoitokäytännöistä haettiin lisätietoa KVO-potilaille sekä heitä hoitaville lääkäreille suunnatulla kyselyllä. Työ on tehty elokuun 2015 ja marraskuun 2016 välisenä aikana. Kroonisen väsymysoireyhtymän riskitekijöitä ovat traumaattiset kokemukset, aiempi masennus, yliaktiivinen elämäntapa ja täydellisyyden tavoittelu mutta toisaalta myös passiivisuus tai liikunnan välttely. Immuunijärjestelmä, neuroendokriininen järjestelmä ja autonominen hermosto ovat osallisia oireyhtymän patofysiologiassa. Pitkäkestoisella stressillä näyttää olevan tärkeä välittävä rooli. Kroonisen väsymysoireyhtymän diagnostiikassa oleellista on muiden väsymystä aiheuttavien, mahdollisesti henkeä uhkaavien, sairauksien poissulku. Erotusdiagnostiikkaa tehdään myös muiden väsymyksenä ilmenevien oireyhtymien tunnistamiseksi. Taudinmääritykseen on käytettävissä useita erilaisia kansainvälisiä diagnostisia kriteeristöjä. Kansallisia hoitosuosituksia tarvittaisiin yhdenmukaistamaan KVO-potilaiden nykyisellään kirjavaa diagnostiikkaa ja hoitoa Suomessa. Porrastettu fyysinen harjoittelu ja kognitiivis-behavioraalinen terapia ovat pitkään olleet ainoita hoitoja, joiden vaikuttavuudesta on kohtalaista näyttöä. Käytössä on myös lääkkeitä ja terapioita, joita on tutkittu vain hyvin vähän tai ei ollenkaan. Rintatolimodi ja rituksimabi ovat laskimonsisäisesti annosteltavia lääkeaineita, joilla näyttö KVO-potilaiden fyysisen toimintakyvyn parantajina on heikko. Sama pätee muun muassa suun kautta annosteltuun hydrokortisoniin, yrttilääkkeisiin ja ravintolisiin.peerReviewedVertaisarvioit

Draft genome sequence of Calothrix 336/3, novel H2 producing cyanobacterium isolated from Finnish lake

We announce the draft genome sequence of Calothrix strain 336/3, an N2-fixing heterocystous filamentous cyanobacterium isolated from a natural habitat. Calothrix 336/3 produces higher levels of hydrogen than Nostoc punctiforme PCC 73102 and Anabaena strain PCC 7120 and, therefore, is of interest for potential technological applications.Non peer reviewe

Gene expression and organization of thylakoid protein complexes in the PSII-less mutant of Synechocystis sp. PCC 6803

Photosystems I and II (PSI arid PSII) are the integral components of the photosynthetic electron transport chain that utilize light to provide chemical energy for CO2 fixation. In this study, we investigated how the deficiency of PSII affects the gene expression, accumulation, and organization of thylakoid protein complexes as well as physiological characteristics of Synechocystis sp. PCC 6803 by combining biochemical, biophysical, and transcriptomic approaches. RNA-seq analysis showed upregulated expression of genes encoding the PSII core proteins, and downregulation of genes associated with interaction between light-harvesting phycobilisomes and PSI. Two-dimensional separation of thylakoid protein complexes confirmed the lack of PSII complexes, yet unassembled PSII subunits were detected. The content of PsaB representing PSI was lower, while the content of cytochrome b(6)f complexes was higher in the PSII-less strain as compared with control (CS). Application of oxygraph measurements revealed higher rates of dark respiration and lower PSI activity in the mutant. The latter likely resulted from the detected decrease in the accumulation of PSI, PSI monomerization, increased proportion of energetically decoupled phycobilisomes in PSII-less cultures, and low abundance of phycocyanin. Merging the functional consequences of PSII depletion with differential protein and transcript accumulation in the mutant, in comparison to CS, identified signal transduction from the photosynthetic apparatus to the genome level.</p

Histone deacetylase inhibitors valproate and trichostatin A are toxic to neuroblastoma cells and modulate cytochrome P450 1A1, 1B1 and 3A4 expression in these cells

Histone deacetylase inhibitors such as valproic acid (VPA) and trichostatin A (TSA) were shown to exert antitumor activity. Here, the toxicity of both drugs to human neuroblastoma cell lines was investigated using MTT test, and IC50 values for both compounds were determined. Another target of this work was to evaluate the effects of both drugs on expression of cytochrome P450 (CYP) 1A1, 1B1 and 3A4 enzymes, which are known to be expressed in neuroblastoma cells. A malignant subset of neuroblastoma cells, so-called N-type cells (UKF-NB-3 cells) and the more benign S-type neuroblastoma cells (UKF-NB-4 and SK-N-AS cell lines) were studied from both two points of view. VPA and TSA inhibited the growth of neuroblastoma cells in a dose-dependent manner. The IC50 values ranging from 1.0 to 2.8 mM and from 69.8 to 129.4 nM were found for VPA and TSA, respectively. Of the neuroblastoma tested here, the N-type UKF-NB-3 cell line was the most sensitive to both drugs. The different effects of VPA and TSA were found on expression of CYP1A1, 1B1 and 3A4 enzymes in individual neuroblastoma cells tested in the study. Protein expression of all these CYP enzymes in the S-type SK-N-AS cell line was not influenced by either of studied drugs. On the contrary, in another S-type cell line, UKF-NB-4, VPA and TSA induced expression of CYP1A1, depressed levels of CYP1B1 and had no effect on expression levels of CYP3A4 enzyme. In the N-type UKF-NB-3 cell line, the expression of CYP1A1 was strongly induced, while that of CYP1B1 depressed by VPA and TSA. VPA also induced the expression of CYP3A4 in this neuroblastoma cell line

Limited effect of chronic valproic acid treatment in a mouse model of Machado-Joseph disease

Machado-Joseph disease (MJD) is an inherited neurodegenerative disease, caused by a CAG repeat expansion within the coding region of ATXN3 gene, and which currently lacks effective treatment. In this work we tested the therapeutic efficacy of chronic treatment with valproic acid (VPA) (200mg/kg), a compound with known neuroprotection activity, and previously shown to be effective in cell, fly and nematode models of MJD. We show that chronic VPA treatment in the CMVMJD135 mouse model had limited effects in the motor deficits of these mice, seen mostly at late stages in the motor swimming, beam walk, rotarod and spontaneous locomotor activity tests, and did not modify the ATXN3 inclusion load and astrogliosis in affected brain regions. However, VPA chronic treatment was able to increase GRP78 protein levels at 30 weeks of age, one of its known neuroprotective effects, confirming target engagement. In spite of limited results, the use of another dosage of VPA or of VPA in a combined therapy with molecules targeting other pathways, cannot be excluded as potential strategies for MJD therapeuticsPM received funding from Ataxia UK Grant (Project: Pharmacologic therapy for Machado-Joseph disease: from a C. elegans drug screen to a mouse model validation). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.info:eu-repo/semantics/publishedVersio

The influence of national culture on management control systems

This master’s thesis aims to point out if national culture has an influence on the use of management control systems. The focus in on studying possible differences found in cultural attributes between Finland and USA. Identified differences are then compared against differences found in management control systems and practices used in these two countries. Geert Hofstede’s original typology of four cultural dimensions is utilized as a basis for identifying and interpreting cultural differences between Finland and USA. Cultural dimensions which are used to identify cultural differences include power distance, individualism, masculinity, and uncertainty avoidance. Management control alternatives are examined by dividing them into four groups: results controls, action controls, personnel controls, and cultural controls, based on the work of Merchant and Van der Stede. The study presents assumptions between possible relations of cultural attributes and the control alternatives. The empirical part of the study was conducted in spring 2014. In order to give the thesis a Finnish view of American culture, four Finnish individuals, who all have worked in the United States for two years or more, were interviewed. The interviews focused on perceptions made at work in US organizations. The interviewees were inquired of their experiences considering differences in national culture, and differences identified between management practices between Finland and USA. Findings from the interviews are then compared against Hofstede’s cultural dimensions, in order to see if a correlation to Hofstede’s results can be identified. Management control alternatives are discussed in the light of the findings, in order to point out whether differences in management control practices are visible. Based on the results it can be stated, that the influence of national culture is visible when comparing management control systems used in Finland and USA