Browsing by Subject "humans"

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  • Altavilla, Riccardo; Caso, Valeria; Bandini, Fabio; Agnelli, Giancarlo; Tsivgoulis, Georgios; Yaghi, Shadi; Furie, Karen L.; Tadi, Prasanna; Becattini, Cecilia; Zedde, Marialuisa; Abdul-Rahim, Azmil H.; Lees, Kennedy R.; Alberti, Andrea; Venti, Michele; Acciarresi, Monica; D'Amore, Cataldo; Mosconi, Maria Giulia; Cimini, Ludovica Anna; Fusaro, Jessica; Bovi, Paolo; Carletti, Monica; Rigatelli, Alberto; Cappellari, Manuel; Putaala, Jukka; Tomppo, Liisa; Tatlisumak, Turgut; Marcheselli, Simona; Pezzini, Alessandro; Poli, Loris; Padovani, Alessandro; Masotti, Luca; Vannucchi, Vieri; Sohn, Sung-Il; Lorenzini, Gianni; Tassi, Rossana; Guideri, Francesca; Acampa, Maurizio; Martini, Giuseppe; Ntaios, George; Athanasakis, George; Makaritsis, Konstantinos; Karagkiozi, Efstathia; Vadikolias, Konstantinos; Liantinioti, Chrysoula; Chondrogianni, Maria; Mumoli, Nicola; Consoli, Domenico; Galati, Franco; Sacco, Simona; Carolei, Antonio; Tiseo, Cindy; Corea, Francesco; Ageno, Walter; Bellesini, Marta; Silvestrelli, Giorgio; Ciccone, Alfonso; Lanari, Alessia; Scoditti, Umberto; Denti, Licia; Mancuso, Michelangelo; Maccarrone, Miriam; Ulivi, Leonardo; Orlandi, Giovanni; Giannini, Nicola; Gialdini, Gino; Tassinari, Tiziana; De Lodovici, Maria Luisa; Bono, Giorgio; Rueckert, Christina; Baldi, Antonio; D'Anna, Sebastiano; Toni, Danilo; Letteri, Federica; Giuntini, Martina; Lotti, Enrico Maria; Flomin, Yuriy; Pieroni, Alessio; Kargiotis, Odysseas; Karapanayiotides, Theodore; Monaco, Serena; Baronello, Mario Maimone; Csiba, Laszlo; Szabo, Lilla; Chiti, Alberto; Giorli, Elisa; Del Sette, Massimo; Imberti, Davide; Zabzuni, Dorjan; Doronin, Boris; Volodina, Vera; Michel, Patrik; Vanacker, Peter; Barlinn, Kristian; Pallesen, Lars-Peder; Barlinn, Jessica; Deleu, Dirk; Melikyan, Gayane; Ibrahim, Faisal; Akhtar, Naveed; Gourbali, Vanessa; Paciaroni, Maurizio (2019)
    Background and Purpose- Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods- We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results- Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients (P=0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4-3.7; P Conclusions- Our findings suggest that patients receiving low-molecular-weight heparin have a higher risk of early ischemic recurrence and hemorrhagic transformation compared with nonbridged patients.
  • Jokinen, Hanna; Koikkalainen, Juha; Laakso, Hanna M.; Melkas, Susanna; Nieminen, Tuomas; Brander, Antti; Korvenoja, Antti; Rueckert, Daniel; Barkhof, Frederik; Scheltens, Philip; Schmidt, Reinhold; Fazekas, Franz; Madureira, Sofia; Verdelho, Ana; Wallin, Anders; Wahlund, Lars-Olof; Waldemar, Gunhild; Chabriat, Hugues; Hennerici, Michael; O'Brien, John; Inzitari, Domenico; Lötjönen, Jyrki; Pantoni, Leonardo; Erkinjuntti, Timo (2020)
    Background and Purpose- Cerebral small vessel disease is characterized by a wide range of focal and global brain changes. We used a magnetic resonance imaging segmentation tool to quantify multiple types of small vessel disease-related brain changes and examined their individual and combined predictive value on cognitive and functional abilities. Methods- Magnetic resonance imaging scans of 560 older individuals from LADIS (Leukoaraiosis and Disability Study) were analyzed using automated atlas- and convolutional neural network-based segmentation methods yielding volumetric measures of white matter hyperintensities, lacunes, enlarged perivascular spaces, chronic cortical infarcts, and global and regional brain atrophy. The subjects were followed up with annual neuropsychological examinations for 3 years and evaluation of instrumental activities of daily living for 7 years. Results- The strongest predictors of cognitive performance and functional outcome over time were the total volumes of white matter hyperintensities, gray matter, and hippocampi (P
  • Silventoinen, Karri; Helle, Samuli; Nisen, Jessica; Martikainen, Pekka; Kaprio, Jaakko (2013)
  • Tikkanen, Emmi; Minicocci, Ilenia; Hällfors, Jenni; Di Costanzo, Alessia; D'Erasmo, Laura; Poggiogalle, Eleonora; Donini, Lorenzo Maria; Wurtz, Peter; Jauhiainen, Matti; Olkkonen, Vesa M.; Arca, Marcello (2019)
    Objective- Loss-of-function (LOF) variants in the ANGPTL3 (angiopoietin-like protein 3) have been associated with low levels of plasma lipoproteins and decreased coronary artery disease risk. We aimed to determine detailed metabolic effects of genetically induced ANGPTL3 deficiency in fasting and postprandial state. Approach and Results- We studied individuals carrying S17X LOF mutation in ANGPTL3 (6 homozygous and 32 heterozygous carriers) and 38 noncarriers. Nuclear magnetic resonance metabolomics was used to quantify 225 circulating metabolic measures. We compared metabolic differences between LOF carriers and noncarriers in fasting state and after a high-fat meal. In fasting, ANGPTL3 deficiency was characterized by similar extent of reductions in LDL (low-density lipoprotein) cholesterol (0.74 SD units lower concentration per LOF allele [95% CI, 0.42-1.06]) as observed for many TRL (triglyceride-rich lipoprotein) measures, including VLDL (very-low-density lipoprotein) cholesterol (0.75 [95% CI, 0.45-1.05]). Within most lipoprotein subclasses, absolute levels of cholesterol were decreased more than triglycerides, resulting in the relative proportion of cholesterol being reduced within TRLs and their remnants. Further, beta-hydroxybutyrate was elevated (0.55 [95% CI, 0.21-0.89]). Homozygous ANGPTL3 LOF carriers showed essentially no postprandial increase in TRLs and fatty acids, without evidence for adverse compensatory metabolic effects. Conclusions- In addition to overall triglyceride- and LDL cholesterol-lowering effects, ANGPTL3 deficiency results in reduction of cholesterol proportion within TRLs and their remnants. Further, ANGPTL3 LOF carriers had elevated ketone body production, suggesting enhanced hepatic fatty acid beta-oxidation. The detailed metabolic profile in human knockouts of ANGPTL3 reinforces inactivation of ANGPTL3 as a promising therapeutic target for decreasing cardiovascular risk.
  • FinnGen Project; Ripatti, Pietari; Rämö, Joel T.; Mars, Nina J.; Fu, Yu; Lin, Jake; Söderlund, Sanni; Benner, Christian; Surakka, Ida; Kiiskinen, Tuomo; Havulinna, Aki S.; Palta, Priit; Freimer, Nelson B.; Widén, Elisabeth; Salomaa, Veikko; Tukiainen, Taru; Pirinen, Matti; Palotie, Aarno; Taskinen, Marja-Riitta; Ripatti, Samuli (2020)
    Background: Hyperlipidemia is a highly heritable risk factor for coronary artery disease (CAD). While monogenic familial hypercholesterolemia associates with severely increased CAD risk, it remains less clear to what extent a high polygenic load of a large number of LDL (low-density lipoprotein) cholesterol (LDL-C) or triglyceride (TG)-increasing variants associates with increased CAD risk. Methods: We derived polygenic risk scores (PRSs) with approximate to 6M variants separately for LDL-C and TG with weights from a UK Biobank-based genome-wide association study with approximate to 324K samples. We evaluated the impact of polygenic hypercholesterolemia and hypertriglyceridemia to lipid levels in 27 039 individuals from the National FINRISK Study (FINRISK) cohort and to CAD risk in 135 638 individuals (13 753 CAD cases) from the FinnGen project (FinnGen). Results: In FINRISK, median LDL-C was 3.39 (95% CI, 3.38-3.40) mmol/L, and it ranged from 2.87 (95% CI, 2.82-2.94) to 3.78 (95% CI, 3.71-3.83) mmol/L between the lowest and highest 5% of the LDL-C PRS distribution. Median TG was 1.19 (95% CI, 1.18-1.20) mmol/L, ranging from 0.97 (95% CI, 0.94-1.00) to 1.55 (95% CI, 1.48-1.61) mmol/L with the TG PRS. In FinnGen, comparing the highest 5% of the PRS to the lowest 95%, CAD odds ratio was 1.36 (95% CI, 1.24-1.49) for the LDL-C PRS and 1.31 (95% CI, 1.19-1.43) for the TG PRS. These estimates were only slightly attenuated when adjusting for a CAD PRS (odds ratio, 1.26 [95% CI, 1.16-1.38] for LDL-C and 1.24 [95% CI, 1.13-1.36] for TG PRS). Conclusions: The CAD risk associated with a high polygenic load for lipid-increasing variants was proportional to their impact on lipid levels and partially overlapping with a CAD PRS. In contrast with a PRS for CAD, the lipid PRSs point to known and directly modifiable risk factors providing additional guidance for clinical translation.
  • Saaros, Anna (Helsingin yliopisto, 2021)
    Tausta: Verbaalisia kuulohallusinaatioita, eli selkeästä puheesta koostuvia harha-aistimuksia, esiintyy sekä psykoottista häiriötä sairastavilla että terveillä ihmisillä. Tutkielmassa selvitetään, mitä eroja ja samankaltaisuuksia verbaalisissa kuulohallusinaatioissa sekä niihin liittyvissä tekijöissä on psykoottista häiriötä sairastavien ja terveiden välillä. Menetelmät: Tutkimusmenetelmänä käytettiin systemaattista kirjallisuuskatsausta. Kirjallisuushaku tehtiin Ovid Medline- ja Pubmed-tietokannoista. Katsauksen aineistoon sisällytettiin yhteensä 28 alkuperäisartikkelia, jotka valikoitiin mukaanotto- ja poissulkukriteerien mukaisesti. Tulokset: Verbaaliset kuulohallusinaatiot olivat sisällöltään negatiivisempia ja aiheuttivat enemmän kuormitusta psykoosipotilailla kuin terveillä. Psykoosipotilaat uskoivat terveitä useammin kuulohallusinaatioiden olevan pahantahtoisia. Terveillä kuulohallusinaatiot esiintyivät harvemmin, kestivät vähemmän kerrallaan, alkoivat nuorempana, olivat paremmin kontrolloitavissa ja häiritsivät vähemmän arkea. Samankaltaisia kuulohallusinaatioiden kliinisiä piirteitä olivat eri äänten lukumäärä, äänen paikantaminen ja äänenvoimakkuus. Lapsuuden psyykkiset traumat olivat verbaalisia kuulohallusinaatioita kokevilla yleisempiä kuin muulla väestöllä. Terveistä ääniä kuulevista suurin osa ei hakeutunut hoitoon kuulohallusinaatioiden takia, mutta heillä oli muuta tervettä väestöä suurempi tarve hakeutua hoitoon muiden mielenterveyden ongelmien takia. Pohdinta: Terveiden ja psykoosipotilaiden verbaalisten kuulohallusinaatioiden piirteissä löytyi sekä eroja että samankaltaisuuksia. Psyykkiset traumat saattavat toimia riskitekijänä kuulohallusinaatioiden alkamiselle. Verbaaliset kuulohallusinaatiot liittyvät muutoksiin aivoissa, mutta ei tiedetä, onko niiden syntymekanismi samanlainen psykoottista häiriötä sairastavien ja terveiden välillä. Psykoosipotilaiden ja terveiden verbaalisten kuulohallusinaatioiden eroihin vaikuttavista tekijöistä ja syntymekanismeista tarvitaan jatkotutkimusta.