Kestävän kehityksen torille 2020 : Skenaarioraportti

Agora 2020 - Towards Sustainable Development 2020. Scenario report, in Finnish, Abstract in English

Amniotic fluid and umbilical cord serum erythropoietin in term and prolonged pregnancies

Objective: Erythropoietin - a hormone regulating erythropoiesis - is a biomarker of chronic fetal hypoxia. High erythropoietin levels in fetal plasma and amniotic fluid are associated with increased risk of adverse neonatal outcome. Since the risk of perinatal morbidity and mortality is increased in pregnancies beyond 41 gestational weeks, we evaluated erythropoietin levels in amniotic fluid and umbilical cord serum in apparently low-risk term (>= 37 gestational weeks) and prolonged pregnancies (>= 41 gestational weeks) with labor induction. Study design: This prospective cohort study comprised 93 singleton pregnancies at 37(+0)-42(+1) gestational weeks, of which prolonged pregnancies numbered 63 (67.7%). Amniotic fluid samples were collected at time of labor induction by amniotomy. Umbilical cord blood samples for evaluation of pH, base excess, and umbilical cord serum erythropoietin were collected at birth. Erythropoietin levels were measured by immunochemiluminometric assay. Normal value of amniotic fluid erythropoietin level was defined as = 27 IU/L. Normal umbilical cord serum erythropoietin was defined as <40 IU/L. Data on maternal pregnancy and delivery characteristics and short-term neonatal outcomes such as Apgar score were obtained from the hospital charts. Associations were calculated using Spearman's rank correlation coefficient. The Chi-square test, Fisher's exact test and the Mann-Whitney U test were utilized to determine differences in the study groups. Results: Amniotic fluid erythropoietin levels correlated with gestational age (r = 0.261, p = 0.012) and were higher among prolonged pregnancies as compared to term pregnancies (p = 0.005). There were 78 (83.9%) vaginal deliveries, and among these erythropoietin levels in amniotic fluid correlated with the levels in umbilical cord serum (r = 0.513, p <0.000). Umbilical cord serum erythropoietin levels correlated with gestational age among vaginal deliveries (r = 0.250, p = 0.027). Erythropoietin levels in amniotic fluid and umbilical cord serum did not correlate with umbilical artery pH or base excess, or other adverse pregnancy outcome. Conclusions: In vaginal deliveries erythropoietin levels in amniotic fluid correlated with the levels in umbilical cord serum. Erythropoietin levels correlated with gestational age, probably due to weakening placental function and relative hypoxemia occurring in advanced gestation. However, in this relatively low-risk study population erythropoietin was not related to adverse delivery outcome. (C) 2018 Elsevier B.V. All rights reserved.Peer reviewe

Alterations of Cardiac Protein Kinases in Cyclic Nucleotide-Dependent Signaling Pathways in Human Ischemic Heart Failure

ObjectivesImpaired protein kinase signaling is a hallmark of ischemic heart disease (IHD). Inadequate understanding of the pathological mechanisms limits the development of therapeutic approaches. We aimed to identify the key cardiac kinases and signaling pathways in patients with IHD with an effort to discover potential therapeutic strategies.MethodsCardiac kinase activity in IHD left ventricle (LV) and the related signaling pathways were investigated by kinomics, transcriptomics, proteomics, and integrated multi-omics approach.ResultsProtein kinase A (PKA) and protein kinase G (PKG) ranked on top in the activity shift among the cardiac kinases. In the IHD LVs, PKA activity decreased markedly compared with that of controls (62% reduction, p = 0.0034), whereas PKG activity remained stable, although the amount of PKG protein increased remarkably (65%, p = 0.003). mRNA levels of adenylate cyclases (ADCY 1, 3, 5, 9) and cAMP-hydrolysing phosphodiesterases (PDE4A, PDE4D) decreased significantly, although no statistically significant alterations were observed in that of PKGs (PRKG1 and PRKG2) and guanylate cyclases (GUCYs). The gene expression of natriuretic peptide CNP decreased remarkably, whereas those of BNP, ANP, and neprilysin increased significantly in the IHD LVs. Proteomics analysis revealed a significant reduction in protein levels of “Energy metabolism” and “Muscle contraction” in the patients. Multi-omics integration highlighted intracellular signaling by second messengers as the top enriched Reactome pathway.ConclusionThe deficiency in cAMP/PKA signaling pathway is strongly implicated in the pathogenesis of IHD. Natriuretic peptide CNP could be a potential therapeutic target for the modulation of cGMP/PKG signaling.Peer reviewe

Tankyrase Inhibition Attenuates Cardiac Dilatation and Dysfunction in Ischemic Heart Failure

Hyperactive poly(ADP-ribose) polymerases (PARP) promote ischemic heart failure (IHF) after myocardial infarction (MI). However, the role of tankyrases (TNKSs), members of the PARP family, in pathogenesis of IHF remains unknown. We investigated the expression and activation of TNKSs in myocardium of IHF patients and MI rats. We explored the cardioprotective effect of TNKS inhibition in an isoproterenol-induced zebrafish HF model. In IHF patients, we observed elevated TNKS2 and DICER and concomitant upregulation of miR-34a-5p and miR-21-5p in non-infarcted myocardium. In a rat MI model, we found augmented TNKS2 and DICER in the border and infarct areas at the early stage of post-MI. We also observed consistently increased TNKS1 in the border and infarct areas and destabilized AXIN in the infarct area from 4 weeks onward, which in turn triggered Wnt/β-catenin signaling. In an isoproterenol-induced HF zebrafish model, inhibition of TNKS activity with XAV939, a TNKSs-specific inhibitor, protected against ventricular dilatation and cardiac dysfunction and abrogated overactivation of Wnt/β-catenin signaling and dysregulation of miR-34a-5p induced by isoproterenol. Our study unravels a potential role of TNKSs in the pathogenesis of IHF by regulating Wnt/β-catenin signaling and possibly modulating miRNAs and highlights the pharmacotherapeutic potential of TNKS inhibition for prevention of IHF

Sirtuin1-p53, forkhead box O3a, p38 and post-infarct cardiac remodeling in the spontaneously diabetic Goto-Kakizaki rat

Peer reviewe

Monoterpenes’ oxidation capacity and rate over a boreal forest : temporal variation and connection to growth of newly formed particles

Peer reviewe

Peltojen kipsikäsittely fosforikuormituksen hallinnassa : Pilottina Savijoen valuma-alue

Julkaisua on päivitetty 17.1.2023: Sivun 53 taulukossa on korjattu Mg mgl-1, P mgl-1 ja PH sarakkeiden arvoja. Sivun 68 kuvatekstiä on tarkennettu. Kuvatekstistä on poistettu maininta vuosien 2006–2013 säähavantoijen käyttämisestä sekä lisätty tieto siitä, että mallinnus kuvaa kaikkien maatalouden toimenpiteiden kuormitusmuutosten vaikutusta. Kuvatekstiin on lisätty myös lähde. Sivulle 99 on lisätty tiedot lähteestä (Fleming ym. 2021).Maataloudesta Itämereen päätyvän fosforikuormituksen vähentäminen edellyttää juurisyihin, kuten peltomaan liian korkeisiin fosforipitoisuuksiin puuttumista. Tämän rinnalle tarvitaan myös nopeavaikutteisia keinoja. Peltojen kipsikäsittelyä testattiin Varsinais-Suomen Savijoella, jossa kipsiä levitettiin 1494 peltohehtaarille ja vaikutuksia seurattiin vajaat viisi vuotta. Kipsikäsittelyn jälkeen fosforin ja orgaanisen hiilen huuhtoumat käsittelyalueella pienenivät suhteessa vertailualueeseen. Jos muutos huuhtoumissa tapahtui yksinomaan kipsin ansiosta, ylemmällä seuranta-alueella huuhtoutui 72 % vähemmän hiukkasmaista fosforia kipsillä käsitellyiltä kuin käsittelemättömiltä pelloilta vajaan viiden vuoden keskiarvona. Alemmalla alueella vähennys oli 19 % ja koko käsittelyalueella 34 %. Liuenneen fosforin huuhtoutuminen oli ylemmän alueen kipsillä käsitellyiltä pelloilta 24 % pienempää, mutta alemmalla alueella 13 % suurempaa, jolloin koko alueella nousua oli 3 %. Liuenneen orgaanisen hiilen osalta vähennykset olivat 88 % (ylempi alue), 54 % (alempi alue) ja 64 % (koko alue). Koska noin puolet kipsistä oli vielä maaperässä vajaan viiden vuoden päästä levityksestä, kipsi saattaa edelleen leikata kuormitusta, tosin ajan myötä yhä vähemmän. Liuenneeseen fosforiin kipsillä näyttäisi olevan lyhytaikaisempi ja epävarmempi vaikutus kuin hiukkasmaiseen fosforiin. Kipsikäsittely nosti voimakkaasti peltojen pintamaan johtolukua ja rikkipitoisuutta, mutta vain noin vuoden ajaksi. Kasvuston rikkipitoisuus kaksinkertaistui noin kahden vuoden ajaksi. Kipsin ei havaittu kulkeutuvan kaivovesiin. Mikäli kaivoa käytetään juomavetenä, kaivon ympärille tulee kuitenkin jättää suojavyöhyke, erityisesti karkeammilla maalajeilla. Lumilevityskoe osoitti, että kipsiä ei tule levittää talviolosuhteissa. Routaisessa maassa fosforia epäpuhtautena sisältävä kipsi voi lisätä rehevöittävän fosforin huuhtoutumista. Malliarvioiden mukaan kipsillä voitaisiin vähentää erityisesti Saaristomereen, mutta myös muille merialueille päätyvää fosforikuormitusta. Tämä vähentäisi sisäsaariston levämääriä, mutta nopeaa parannusta Saaristomeren yleisessä tilassa ei ole odotettavissa. Parhaan vaikutuksen saaminen edellyttää myös typpikuormituksen vähentämistä. Kipsin ja rakennekalkin käytön kustannusvaikuttavuuden tarkastelu tuotti kipsikäsittelyn vuotuiseksi kustannusvaikuttavuusluvuksi 58 € poistettua fosforikiloa kohti, kun vain fosforihuuhtouma huomioidaan. Kierrätysmateriaalista valmistelulle rakennekalkille vastaava luku on 75 € kg-1 P ja sivuvirtapohjaiselle rakennekalkille 96 € kg-1 P. Kun myös ilmastovaikutus huomioidaan, kustannusvaikuttavuus on kipsille 59 € kg−1, kierrätysmateriaalista valmistetulle rakennekalkille 90 € kg−1 ja sivuvirtapohjaiselle rakennekalkille 145 € kg−1. Yhteiskunnallinen nettohyöty ottaa huomioon maataloustuotannosta saatavan yksityisen voiton sekä ravinne- ja ilmastohaittojen yhteiskunnallisen arvon. Kipsikäsittelyn nettohyödyn nykyarvo pelkkä ravinnehuuhtoumahaitta huomioiden on 977 € kg−1, ja kierrätysmateriaalista valmistetun rakennekalkin 929 € kg−1 ja sivuvirtapohjaisen rakennekalkin 874 € kg−1. Rakennekalkin käyttö vesiensuojelun tarpeisiin ei välttämättä ole viljelijälle ensisijainen peruste käyttää rakennekalkkia. Hyvän sadontuottokyvyn takia voi olla tarve vaikuttaa maan pH-arvoon kalkituksella ja käyttää joko maatalouskalkkia tai rakennekalkkia. Vesiensuojelun edistämiseksi yksi vaihtoehto olisi, että yhteiskunta tukisi rakennekalkkia sen tuottaman vesiensuojeluhyödyn mukaisesti edellyttäen, että saatavilla on laatuja, joiden ilmastovaikutus on alhainen. Savijoen seurantaa jatketaan KIPSI-hankkeessa, mikä tarkentaa arviota kipsin vaikutuksen kestosta. Kipsikäsittelyn kustannustehokas kohdentaminen edellyttäisi, että kipsin vaikutusmekanismi ja optimaalinen käyttö eri maalajeilla ja muokkausmenetelmillä tunnettaisiin paremmin. Gypsum amendment of agricultural fields – Pilot in the Savijoki catchment Reducing the agricultural phosphorus (P) load into the Baltic Sea calls for decreasing the use of manure and fertilizers in problem areas. However, as soil P reserves decline slowly, there is also a need for interim measures, such as the use of soil amendments. To this end, a pilot study was conducted in southwestern Finland where 1494 hectares of agricultural fields were amended with gypsum (CaSO4 ∙ 2H2O) in autumn 2016. The Savijoki River, draining the pilot area, was monitored before and for almost five years after the gypsum amendment. Monitoring focused on the control area in the upper reaches and two gypsum affected sites in the middle reaches (upper and lower treatment areas). In comparison to the control area, the gypsum amendment resulted in lower losses of P and dissolved organic carbon (DOC). A source apportionment on riverine P loads suggested that the losses of particulate P were 72% lower from the gypsum amended fields than from the nonamended fields in the upper treatment area as a 4.7-year average. Surprisingly, the reduction was only 19% in the lower treatment area, providing an overall reduction of 34% when both areas were considered. The corresponding reduction in the losses of dissolved reactive P was 24% in the upper area, whereas the losses increased by 13% in the lower area and by 3% in the total area. DOC was reduced by 88% (upper area), 54% (lower area) and 64% (total area), but the estimate was uncertain due to problems in source apportionment. Because only approximately half of the gypsum had flushed away after 4.7 years, gypsum may continue to reduce the losses of particulate P and DOC. However, the efficiency is likely to decrease over time. Gypsum amendment increased the electrical conductivity and sulfur concentration in topsoil for one to two years after the amendment. In addition, the sulfur concentration of the cultivated plants increased for two years, but other effects on the soil and plant chemistry were minor. The monitoring of seven private wells showed that gypsum had not leached into the ground water during the five years. If a well is used as a drinking water source, then an untreated buffer zone should be left around the well as a precautionary measure, especially on coarse soils. A snow simulation study showed that gypsum should not be spread on snow or frozen soil because P, an impurity in the phosphogypsum used, may result in elevated losses of dissolved P. Such a risk is eliminated if P-free gypsum species are used, but the desired effect may still be low if gypsum does not have contact with surface soil in winter. According to a nutrient load model, amending all the potentially eligible field parcels with gypsum would result in a substantial reduction in the P load, especially to the eutrophic Archipelago Sea. Because the sea area is in close contact with the Baltic Proper, a rapid improvement in its state is not possible, although gypsum amendment would decrease the algal biomasses in the inner archipelago. The cost effectiveness and social net benefits of gypsum and structure lime were assessed by considering P loads and greenhouse gas emissions. The cost effectiveness figure is the ratio of treatment costs to the achieved reduction in P load. If only the P load is taken into account, then the cost effectiveness figure is 58 € per kg of reduced P for gypsum, 75 € kg−1 P for structure lime from recycled materials and 96 € kg−1 P for structure lime manufactured using lime kiln dust, which is a byproduct of the lime manufacturing process (structure lime from byproduct, in what follows). Additionally, accounting for climate damage slightly increases the costs of gypsum and structure lime from recycled materials and more so for structure lime from byproduct. Social net benefits (net present value, NPV) comprise private profits from cultivation and social valuation of eutrophication and climate damages. When only P loading is taken into account, NPV without soil amendments is 966 € kg-1, 977 € kg−1 for gypsum and 929 € kg−1 for structure lime from recycled materials. The use of gypsum increases social welfare above the baseline cultivation. Structure lime from byproduct provides benefits of 874 € kg−1. Accounting for greenhouse gas emissions decreases all net benefits but does not change above conclusions. Sensitivity analysis shows that higher erosion, higher soil P values and higher eutrophication damage increase the net benefits and desirability of soil amendments. In contrast, a low reduction in P loads or initially low loading makes the use of soil amendments undesirable. The results suggest targeting soil amendments on fields that have either high erosion rates or high soil P reserves. The results also provide grounds for using gypsum and recycled structure lime as complementary and readily effective soil amendments for water protection. To be effective in terms of water protection, structure lime should be cultivated thoroughly into the soil quickly after spreading. Therefore, society should provide farmers with information and instructions on the use of lime. Future research should target the performance of gypsum in different soil types and tillage practices to further improve the cost efficiency of the method. The mechanism, e.g., the role of calcium in maintaining soil microaggregation, should be evaluated, and the mechanism should be incorporated in field-scale models