Novel Ex Vivo DOAC Removal Methods Reduce Interference in Lupus Anticoagulant Testing

Direct oral anticoagulants (DOAC) interfere in laboratory coagulation testing. The aim here was to study how commercial DOAC removal methods, DOAC Filter® and DOAC-Stop™, perform to eliminate DOAC concentrations and false positive results in lupus anticoagulant (LAC) testing. We acquired 50 patient samples with high concentrations of DOACs: apixaban (n = 18, range 68–572 ng/mL), dabigatran (n = 8, range 47–154 ng/mL), edoxaban (n = 8, range 35–580 ng/mL) and rivaroxaban (n = 16, range 69–285 ng/mL). DOACs were removed ex vivo with either DOAC Filter® (n = 28) or DOAC-Stop™ (n = 22). Additionally, commercial control and calibrator samples were studied (n = 13 for DOAC Filter®, n = 14 for DOAC-Stop™). LAC screening was performed before and after DOAC removal. Both DOAC Filter® and DOAC-Stop™ were effective in removing DOAC concentrations in samples: DOAC concentrations decreased to median of 0 ng/mL (range 0–48 ng/mL). Only one sample had more than residual 25 ng/mL of DOAC (apixaban). Before DOAC removal, 96% (48/50) of patient samples and over 90% (12/13 DOAC Filter®, 13/14 DOAC-Stop™) of control/calibrator samples were positive in the LAC screening. In patient samples, LAC screening turned negative in 61% (17/28) after DOAC Filter® and 45% (10/22) after DOAC-Stop™ treatment. All control samples became negative after DOAC removal. In conclusion, DOAC removal ex vivo reduces false positives in LAC screening. DOAC removal halved the need for confirmation or mixing tests- Although a subset of patients would require further testing, DOAC removal reduces unnecessary repeated LAC testing

Metsiin kohdistuvien ilmastopoliittisten toimenpiteiden toteutettavuus ja puun tarjonta yksityisen metsänomistuksen näkökulmasta : Hiilineutraali Suomi 2035 – ilmasto- ja energiapolitiikan toimet ja vaikutukset

Tämä raportti arvioi Hiisi-hankkeessa esitettyjen metsiin kohdistettujen toimenpiteiden toteutettavuutta ja puumarkkinavaikutuksia hyödyntäen kirjallisuuskatsausta metsänomista-jien asennetutkimuksista, ekonometristä analyysiä ja sidosryhmähaastatteluita. Yksityismetsänomistajien merkitys puumarkkinoilla ja hiilinielun tuottajina on merkittävä. Päätökseen toteuttaa ehdotettuja toimenpiteitä metsissä vaikuttavat metsänomistajien asenteet ja näkemykset ilmastonmuutoksesta, metsänomistuksen tavoitteet, metsätilan mahdollisuudet ja taloudelliset tekijät. Suomalaiset metsänomistajat ymmärtävät metsiensä roolin ilmastonmuutoksen hillinnässä. Metsänomistuksen tavoiteryhmien suhtautuminen eri ilmastotoimenpiteisiin vaihtelee suuresti, mikä tulisi ottaa huomioon vaihtoehtoja valitessa. Päätöstä siitä mitä toimenpiteitä voi ja kannattaa toteuttaa metsissä rajoittavat kuitenkin metsätilan ominaisuudet. Puumarkkinoiden ekonometrisen tarkastelun mukaan metsänomistajat reagoivat tehokkaammin hintojen muutokseen ja näin puun tarjontaa voidaan kasvattaa lyhyellä aikavälillä hintoja nostamalla. Ehdotetuista toimenpiteistä osa vähentäisi, osa lisäisi puuntarjontaa. Puumarkkinoiden kysyntä ja tarjonta kasvavat tulevaisuudessa, mutta tukkipuun saannon lisääntymisen ei vastaa nykyistä tuotantorakennetta. Toimenpiteiden toteutuksen edistämisessä olennaisia ohjauskeinoja ovat tuet ja neuvonta. Tavoitteiden saavuttaminen nopealla aikataululla saattaisi edellyttää lisää kannustavia toimia ja vahvaa lisäpanosta neuvonta- ja suunnittelutyöhön. Myös tutkimustietoon ja metsänammattilaisten osaamiseen tulisi panostaa. Hiilineutraali Suomi 2035 – Ilmasto- ja energiapolitiikan toimet ja vaikutukset (HIISI) -hankkeen raportit: Synteesiraportti – Johtopäätökset ja suositukset Maankäyttö- ja maataloussektorin skenaariot Ilmasto- ja energiapolitiikan toimien ympäristövaikutusten arviointi Kansantalouden skenaariot Metsiin kohdistuvien ilmastopoliittisten toimenpiteiden toteutettavuus ja puun tarjonta yksityisen metsänomistuksen näkökulmasta Energiajärjestelmän ja kasvihuonekaasujen kehitykset Tämä julkaisu on toteutettu osana valtioneuvoston selvitys- ja tutkimussuunnitelman toimeenpanoa (tietokayttoon.fi). Julkaisun sisällöstä vastaavat tiedon tuottajat, eikä tekstisisältö välttämättä edusta valtioneuvoston näkemystä

”Tartten aikuisten apua tehtäviin, mutta niitä on kyllä mukava tehdä.”:esikoululaisten näkemyksiä vahvuuksistaan mielenkiinnonkohteistaan ja tuen tarpeistaan: keskustelu symbolein -pelin avulla

Tiivistelmä. Esiopetuksessa lapselle laaditaan yhteistyössä lapsen, huoltajien ja opettajien kanssa pedagoginen suunnitelma, joka ohjaa lapsen koko esiopetusvuoden toimintaa. Tämän yksilöllisen ja tavoitteellisen suunnittelun lähtökohtana ovat lapsen vahvuudet, mielenkiinnonkohteet ja tuen tarpeet. Pedagogisissa asiakirjoissa lapsen oma näkökulma tulee vaihtelevasti esille näkyväksi. Tämän tutkimuksen tarkoituksena on selvittää, miten lapsi kertoo omista vahvuuksistaan, mielenkiinnonkohteistaan ja tuen tarpeistaan Keskustelu symbolein -pelin avulla ja kuinka Keskustelu symbolein -peli tukee lapsen ilmaisua. Tutkimuksessa kuvataan myös, miten lapsen vahvuudet, mielenkiinnonkohteet ja tuen tarpeet on tuotu esille lapsen pedagogisissa asiakirjoissa. Laadullisen tutkimuksen aineisto koostui viiden lapsen Keskustelu symbolein -pelin taulujen valokuvista ja lapsen pedagogisista asiakirjoista. Tutkimuksen aineisto analysoitiin neljässä vaiheessa. Analysoinnissa yhdistettiin sisällönanalyysin ja Barthesin semioottisen kuvatulkintamallin menetelmiä. Tämän tutkimuksen tuloksissa saatiin selville, että Keskustelu symbolein -pelissä lapsen aktiivinen rooli ja omat näkemykset tulivat vahvasti esille. Lisäksi saatiin selville, että Keskustelu symbolein -peli auttoi lapsia tunnistamaan ja tarkemmin pohtimaan omia vahvuuksiaan, mielenkiinnonkohteitaan ja tuen tarpeitaan. Tutkimus osoitti myös, että Keskustelu symbolein -peli tuki lapsen ilmaisua ja oli täten toimiva menetelmä kehityskeskusteluissa käytettäväksi. Tämän tutkimuksen johtopäätöksenä voidaan todeta, että Keskustelu symbolein-peli tuo lasten omat näkökulmat taidoistaan esille laajemmin ja monitahoisemmin verrattuna siihen, mitä lasten pedagogisiin asiakirjoihin oli kirjattu. Keskustelu symbolein-peliä pelatessaan lapsella on aktiivisempi rooli ja valta siitä mitä kertoo. Lapsi sijoittaessaan kuvia eri pohjille pystyy kertomaan omia näkemyksiään, vaikka hänen kielelliset taitonsa eivät siihen riittäisi. Lisäksi lapsi pääsee osallistumaan ja vaikuttamaan oman pedagogisen asiakirjan tekemiseen, kun hänen Keskustelu symbolein -pelissä ilmaisemat näkemyksensä kirjataan siihen

Systemic Inflammation Induced Changes in Protein Expression of ABC Transporters and Ionotropic Glutamate Receptor Subunit 1 in the Cerebral Cortex of Familial Alzheimer`s Disease Mouse Model

Alzheimer's disease (AD) is an incurable disease, with complex pathophysiology and a myriad of proteins involved in its development. In this study, we applied quantitative targeted absolute proteomic analysis for investigation of changes in potential AD drug targets, biomarkers, and transporters in cerebral cortices of lipopolysaccharide (LPS)-induced neuroinflammation mouse model, familial AD mice (APdE9) with and without LPS treatment as compared to age-matched wild type (WT) mice. The ABCB1, ABCG2 and GluN1 protein expression ratios between LPS treated APdE9 and WT control mice were 0.58 (95% CI 0.44-0.72), 0.65 (95% CI 0.53-0.77) and 0.61 (95% CI 0.52-0.69), respectively. The protein expression levels of other proteins such as MGLL, COX-2, CytC, ABCC1, ABCC4, SLC2A1 and SLC7A5 did not differ between the study groups. Overall, the study revealed that systemic inflammation can alter ABCB1 and ABCG2 protein expression in brain in AD, which can affect intra-brain drug distribution and play a role in AD development. Moreover, the inflammatory insult caused by peripheral infection in AD may be important factor triggering changes in GluN1 protein expression. However, more studies need to be performed in order to confirm these findings. The quantitative information about the expression of selected proteins provides important knowledge, which may help in the optimal use of the mouse models in AD drug development and better translation of preclinical data to humans. (c) 2021 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.Peer reviewe

Increased Expression and Activity of Brain Cortical cPLA2 Due to Chronic Lipopolysaccharide Administration in Mouse Model of Familial Alzheimer’s Disease

Cytosolic phospholipase A2 (cPLA2) is an enzyme regulating membrane phospholipid homeostasis and the release of arachidonic acid utilized in inflammatory responses. It represents an attractive target for the treatment of Alzheimer’s disease (AD). Previously, we showed that lipopolysaccharide (LPS)-induced systemic inflammation caused abnormal lipid metabolism in the brain of a transgenic AD mouse model (APdE9), which might be associated with potential changes in cPLA2 activity. Here, we investigated changes in cPLA2 expression and activity, as well as the molecular mechanisms underlying these alterations due to chronic LPS administration in the cerebral cortex of female APdE9 mice as compared to saline- and LPS-treated female wild-type mice and saline-treated APdE9 mice. The study revealed the significant effects of genotype LPS treatment on cortical cPLA2 protein expression and activity in APdE9 mice. LPS treatment resulted in nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) activation in the cortex of APdE9 mice. The gene expressions of inflammation markers Il1b and Tnfa were significantly elevated in the cortex of both APdE9 groups compared to the wild-type groups. The study provides evidence of the elevated expression and activity of cPLA2 in the brain cortex of APdE9 mice after chronic LPS treatment, which could be associated with NFkB activation

PATH2030 – An Evaluation of Finland’s Sustainable Development Policy

The PATH2030 project has produced an evaluation of Finland’s sustainable development policy and formulated concrete recommendations for the future. The evaluation is based on multidisciplinary meth-ods and broad and diverse material in the form of indicators, documents, and expert views gathered through surveys, interviews and workshops. The evaluation focused particularly on the time after the 2030 Agenda entered into force in 2016. No country has yet presented a credible plan for how to reach the goals of the 2030 Agenda. Finland has various national targets and programmes that point in the right direction, but the policy could be more transformative and coherent. Finland’s sustainable development policy has succeeded in being inclusive, which shows that sustainable development has become a broadly accepted aim in society. Reaching the 2030 goals requires, however, many system-level changes and the mediation of conflicts of interest. The evaluation shows that sustainable development policy should focus on climate change, environmental questions, consumption and increasing inequality. It is recommended that sustainable development should become the basis of future Government Programmes, that a roadmap for how to reach the goals should be created and that, for example, the indicators and the Expert Panel on Sustainable Development should be revised. Appendix 1-13 PATH2030: Detailed descriptions of the evaluations and documentation of data collection (separate document, in Finnish) Appendix 14 PATH2030: The 2030 Agenda, foreign policy and human rights (separate document, in Finnish)This publication is part of the implementation of the Government Plan for Analysis, Assessment and Research (tietokayttoon.fi). The content is the responsibility of the producers of the information and does not necessarily represent the view of the Government

Inactivation of mouse transmembrane prolyl 4-hydroxylase increases blood brain barrier permeability and ischemia-induced cerebral neuroinflammation

Hypoxia-inducible factor prolyl 4-hydroxylases (HIF-P4Hs) regulate the hypoxic induction of > 300 genes required for survival and adaptation under oxygen deprivation. Inhibition of HIF-P4H-2 has been shown to be protective in focal cerebral ischemia rodent models, while that of HIF-P4H-1 has no effects and inactivation of HIF-P4H-3 has adverse effects. A trans membrane prolyl 4-hydroxylase (P4H-TM) is highly expressed in the brain and contributes to the regulation of HIF, but the outcome of its inhibition on stroke is yet unknown. To study this, we subjected WT and P4htm(-/- )mice to permanent middle cerebral artery occlusion (pMCAO). Lack of P4H-TM had no effect on lesion size following pMCAO, but increased inflam-matory microgliosis and neutrophil infiltration was observed in the P4htm-/- cortex. Furthermore, both the permeability of blood brain barrier and ultrastructure of cerebral tight junctions were compromised in P4htm(-/-) mice. At the molecular level, P4H-TM deficiency led to increased expression of proinflammatory genes and robust activation of protein kinases in the cortex, while expression of tight junction proteins and the neuroprotective growth factors erythropoietin and vascular endothelial growth factor was reduced. Our data provide the first evidence that P4H-TM inactivation has no protective effect on infarct size and increases inflammatory microgliosis and neutrophil infiltration in the cortex at early stage after pMCAO. When considering HIF-P4H inhibitors as potential therapeutics in stroke, the current data support that isoenzyme-selective inhibitors that do not target P4H-TM or HIF-P4H-3 would be preferred.Peer reviewe

Peripheral inflammation preceeding ischemia impairs neuronal survival through mechanisms involving miR‐127 in aged animals

Envelliment; Inflamació; MicroARNEnvejecimiento; Inflamación; MicroARNAging; Inflammation; MicroRNAIschemic stroke, the third leading cause of death in the Western world, affects mainly the elderly and is strongly associated with comorbid conditions such as atherosclerosis or diabetes, which are pathologically characterized by increased inflammation and are known to influence the outcome of stroke. Stroke incidence peaks during influenza seasons, and patients suffering from infections such as pneumonia prior to stroke exhibit a worse stroke outcome. Earlier studies have shown that comorbidities aggravate the outcome of stroke, yet the mediators of this phenomenon remain obscure. Here, we show that acute peripheral inflammation aggravates stroke‐induced neuronal damage and motor deficits specifically in aged mice. This is associated with increased levels of plasma proinflammatory cytokines, rather than with an increase of inflammatory mediators in the affected brain parenchyma. Nascent transcriptomics data with mature microRNA sequencing were used to identify the neuron‐specific miRNome, in order to decipher dysregulated miRNAs in the brains of aged animals with stroke and co‐existing inflammation. We pinpoint a previously uninvestigated miRNA in the brain, miR‐127, that is highly neuronal, to be associated with increased cell death in the aged, LPS‐injected ischemic mice. Target prediction tools indicate that miR‐127 interacts with several basally expressed neuronal genes, and of these we verify miR‐127 binding to Psmd3. Finally, we report reduced expression of miR‐127 in human stroke brains. Our results underline the impact of peripheral inflammation on the outcome of stroke in aged subjects and pinpoint molecular targets for restoring endogenous neuronal capacity to combat ischemic stroke.This study was supported by Emil Aaltonen Foundation, Academy of Finland and Finnish Cultural Foundation

Inactivation of mouse transmembrane prolyl 4-hydroxylase increases blood brain barrier permeability and ischemia-induced cerebral neuroinflammation

Hypoxia-inducible factor prolyl 4-hydroxylases (HIF-P4Hs) regulate the hypoxic induction of > 300 genes required for survival and adaptation under oxygen deprivation. Inhibition of HIF-P4H-2 has been shown to be protective in focal cerebral ischemia rodent models, while that of HIF-P4H-1 has no effects and inactivation of HIF-P4H-3 has adverse effects. A trans membrane prolyl 4-hydroxylase (P4H-TM) is highly expressed in the brain and contributes to the regulation of HIF, but the outcome of its inhibition on stroke is yet unknown. To study this, we subjected WT and P4htm(-/- )mice to permanent middle cerebral artery occlusion (pMCAO). Lack of P4H-TM had no effect on lesion size following pMCAO, but increased inflam-matory microgliosis and neutrophil infiltration was observed in the P4htm-/- cortex. Furthermore, both the permeability of blood brain barrier and ultrastructure of cerebral tight junctions were compromised in P4htm(-/-) mice. At the molecular level, P4H-TM deficiency led to increased expression of proinflammatory genes and robust activation of protein kinases in the cortex, while expression of tight junction proteins and the neuroprotective growth factors erythropoietin and vascular endothelial growth factor was reduced. Our data provide the first evidence that P4H-TM inactivation has no protective effect on infarct size and increases inflammatory microgliosis and neutrophil infiltration in the cortex at early stage after pMCAO. When considering HIF-P4H inhibitors as potential therapeutics in stroke, the current data support that isoenzyme-selective inhibitors that do not target P4H-TM or HIF-P4H-3 would be preferred.Peer reviewe

Women with polycystic ovary syndrome are burdened with multimorbidity and medication use independent of body mass index at late fertile age : A population-based cohort study

Introduction This population-based follow-up study investigated the comorbidities, medication use, and healthcare services among women with polycystic ovary syndrome (PCOS) at age 46 years. Material and methods The study population derived from the Northern Finland Birth Cohort 1966 and consisted of women reporting oligo/amenorrhea and hirsutism at age 31 years and/or a PCOS diagnosis by age 46 years (n = 246) and controls without PCOS symptoms or diagnosis (n = 1573), referred to as non-PCOS women. The main outcome measures were self-reported data on symptoms, diagnosed diseases, and medication and healthcare service use at the age of 46 years. Results Overall morbidity risk was increased by 35% (risk ratio [RR] 1.35, 95% confidence interval [CI] 1.16-1.57) and medication use by 27% [RR 1.27, 95% CI 1.08-1.50) compared with non-PCOS women, and the risk remained after adjusting for body mass index. Diagnoses with increased prevalence in women with PCOS were migraine, hypertension, tendinitis, osteoarthritis, fractures, and endometriosis. PCOS was also associated with autoimmune diseases and recurrent upper respiratory tract infections and symptoms. Interestingly, healthcare service use did not differ between the study groups after adjusting for body mass index. Conclusions Women with PCOS are burdened with multimorbidity and higher medication use, independent of body mass index.Peer reviewe