Pikkukeskosten ravitsemushoito tehohoitovaiheen aikana

Ennenaikaisesti syntyneen lapsen suolisto ei heti ole kypsä käsittelemään suun kautta annettua ravintoa. Pikkukeskosen kasvun ja kehityksen tukemiseksi tarvitaan äidinmaidon lisäksi suonensisäistä ravitsemushoitoa. Tarkoituksena oli selvittää, minkälaista ravitsemushoitoa pikkukeskoset saivat vastasyntyneiden teho-osastolla kahden ensimmäisen elinviikon aikana. Saatuja tuloksia verrattiin kansainvälisiin suosituksiin sekä 2000-luvun alussa tehtyyn vastaavanlaiseen selvitykseen. Tutkimuskohteena olivat HUS Lasten ja nuorten sairaalan vastasyntyneiden teho-osastolla hoidetut alle 1501-grammaisina vuonna 2009 syntyneet lapset. Osaston tietojärjestelmän ja sairauskertomusmerkintöjen avulla selvitettiin retrospektiivisesti 147 pikkukeskosen päivittäinen ravinnonsaanti kahden ensimmäisen elinviikon aikana, lisäksi seurattiin lasten kasvua. Tilastolliseen analyysiin käytettiin Pearsonin ja Spearmanin korrelaatiotestejä. Lasten kokonaisenergiansaanti kohosi ripeästi ensimmäisinä elinpäivinä ja tasoittui 105 kcal/kg/vrk tuntumaan. Parenteraalinen energiansaanti hallitsi alussa, mutta väheni enteraalisen ravitsemuksen lisääntyessä. Proteiininsaanti lisääntyi nopeasti tasolle 2,5 g/kg/vrk. Yli puolet pikkukeskosista saavutti kokonaisenergiansaannin 90 kcal/kg/vrk neljäntenä hoitopäivänä. Vain pieni osa lapsista saavutti tutkimusjakson aikana proteiininsaannin 3 g/kg/vrk. 2000-luvun alun jälkeen pikkukeskosten varhaista proteiininsaantia ja erityisesti hyvin pienipainoisten keskosten parenteraalista ravitsemusta on tehostettu

Automatic text summarization

Automatic text summarization has been a rapidly developing research area in natural language processing for the last 70 years. The development has progressed from simple heuristics to neural networks and deep learning. Both extractive and abstractive methods have maintained their interest to this day. In this thesis, we will research different methods on automatic text summarization and evaluate their capability to summarize text written in Finnish. We will build an extractive summarizer and evaluate how well it performs on Finnish news data. We also evaluate the goodness of the news data to see can it be used in the future to develop a deep learning based summarizer. The obtained ROUGE scores tell that the performance is not what is expected today from a generic summarizer. On the other hand, the qualitative evaluation reveals that the generated summaries often are more factual than the gold standard summaries in the data set

Carryover effects of environmental stressors influence the life performance of brown trout

Carryover effects of environmental stressors occur when experiences of the environment in earlier life stages or seasons influence the performance of individuals later in life. These can be especially critical for species that have diverse developmental transition periods in their life cycle, such as salmonid fish. Sublethal changes in metabolism, size, or growth experienced in early life stages may have a long-lasting effect on the subsequent life performance of these species, but very few studies have formally tested these changes in relation to environmental stressors. Here, we investigated whether different types of fine sediment result in carryover effects that change the life performance of migratory brown trout. First, we manipulated the early habitat conditions of brown trout through the life stages from egg to fry by incubating them in varying substrate treatments (i.e., gravel without added sediment, gravel with added fine sand, and gravel with added organic matter). Exposure to fine sediment during early development had serious effects on the metabolism, size, escape responses, timing of emergence, and potential survival of early life stages. These carryover effects were persistent and remained present over the critical life shift from relying on parentally provided resources as immobile eggs to independent exogenous feeding as parr. Second, fish were relocated as parr to either their original or different treatment environments and their metabolism, size, and growth were reanalyzed. The effects of environmental stress were observed later in their life cycle when fry from the gravel treatment were relocated to sand or organic-rich treatments. These were found to be significantly smaller in size and had a higher metabolic rate than fry maintained in their original treatment environment. Together, our study experimentally demonstrated that the carryover effects of environmental stressors experienced in early stages may influence the fitness outcomes of migratory fish later in life. We suggest that sublethal environmental stressors should be better considered in restoration schemes and management strategies to reverse the current trend of declining salmonid populations

Objectively measured preoperative physical activity and sedentary behaviour among Finnish patients scheduled for elective cardiac procedures : baseline results from randomized controlled trial

Background: We investigated preoperative physical activity (PA) and sedentary behaviour (SB) in patients scheduled for elective cardiac procedures and compared them with population-based sample of Finnish adults. Methods: Cardiac patients (n=139) undergoing cardiac operations carried a triaxial accelerometer for seven days during the month before the procedure. Patients were categorised into four groups according to the procedure: percutaneous coronary intervention or coronary angiography (PCI-CA), coronary artery bypass grafting (CABG), aortic valve replacement (AVR) and mitral valve surgery (MVS). The raw accelerometer data was analyzed with dedicated algorithms to determine metabolic equivalents (METs, 3.5 mL/kg/min of oxygen consumption) of PA. The intensity of PA was divided into two categories: light (LPA, 1.5-2.9 METs) and moderate-to-vigorous (MVPA, >= 3.0 METs), while SB represented intensity < 1.5 MET without movements. SB and PA were described as daily means and accumulation from different bout lengths. Daily standing, steps and mean and peak MET-values were calculated. The results were compared between the patient groups and against the reference group from a population-based study FinFit2017. Results: Cardiac patients had fewer daily steps than the FinFit population (p= 0.01), and less SB accumulating from 10 min bouts (p< 0.001) than the FinFit population. Conclusions: We found large differences in PA and SB between the patient groups and the FitFit population, CABG group having the worst activity profile. Also, the variation within the patient groups was wide, which should be considered to individualise the rehabilitation programs postoperatively.Peer reviewe

Sortilin-related receptor is a druggable therapeutic target in breast cancer

In breast cancer, the currently approved anti-receptor tyrosine-protein kinase erbB-2 (HER2) therapies do not fully meet the expected clinical goals due to therapy resistance. Identifying alternative HER2-related therapeutic targets could offer a means to overcome these resistance mechanisms. We have previously demonstrated that an endosomal sorting protein, sortilin-related receptor (SorLA), regulates the traffic and signaling of HER2 and HER3, thus promoting resistance to HER2-targeted therapy in breast cancer. This study aims to assess the feasibility of targeting SorLA using a monoclonal antibody. Our results demonstrate that anti-SorLA antibody (SorLA ab) alters the resistance of breast cancer cells to HER2 monoclonal antibody trastuzumab in vitro and in ovo. We found that SorLA ab and trastuzumab combination therapy also inhibits tumor cell proliferation and tumor cell density in a mouse xenograft model of HER2-positive breast cancer. In addition, SorLA ab inhibits the proliferation of breast cancer patient-derived explant three-dimensional cultures. These results provide, for the first time, proof of principle that SorLA is a druggable target in breast cancer.Peer reviewe

Pain process of patients with cardiac surgery — Semantic annotation of electronic patient record data

Aims and objectives: To describe and compare the pain process of the patients’ with cardiac surgery through nurses’ and physicians’ documentations in the electronic patient records.Background: Postoperative pain assessment and management should be documented regularly, to ensure optimal pain care process for patients. Despite availability of evidence‐based guidelines, pain assessment and documentation remain inadequate.Design: A retrospective patients’ record review.Methods: The original data consisted of the electronic patient records of 26,922 patients with a diagnosed heart disease. A total of 1,818 care episodes of patients with cardiac surgery were selected from the data. We used random sampling to obtain 280 care episodes for annotation. These 280 care episodes contained 2,156 physician reports and 1,327 days of nursing notes. We developed an annotation manual and schema, and then, we manually conducted semantic annotation on care episodes, using the Brat annotation tool. We analysed the annotation units using thematic analysis. Consolidated criteria for reporting qualitative research guideline was followed in reporting where appropriate in this study design.Results: We discovered expressions of six different aspects of pain process: (a) cause, (b) situation, (c) features, (d) consequences, (e) actions and (f) outcomes. We determined that five of the aspects existed chronologically. However, the features of pain were simultaneously existing. They indicated the location, quality, intensity, and temporality of the pain and they were present in every phase of the patient’s pain process. Cardiac and postoperative pain documentations differed from each other in used expressions and in the quantity and quality of descriptions.Conclusion: We could construct a comprehensive pain process of the patients with cardiac surgery from several electronic patient records. The challenge remains how to support systematic documentation in each patient.Relevance to clinical practice: The study provides knowledge and guidance of pain process aspects that can be used to achieve an effective pain assessment and more comprehensive documentation.<br /

Sortilin-related receptor is a druggable therapeutic target in breast cancer

In breast cancer, the currently approved anti-receptor tyrosine-protein kinase erbB-2 (HER2) therapies do not fully meet the expected clinical goals due to therapy resistance. Identifying alternative HER2-related therapeutic targets could offer a means to overcome these resistance mechanisms. We have previously demonstrated that an endosomal sorting protein, sortilin-related receptor (SorLA), regulates the traffic and signaling of HER2 and HER3, thus promoting resistance to HER2-targeted therapy in breast cancer. This study aims to assess the feasibility of targeting SorLA using a monoclonal antibody. Our results demonstrate that anti-SorLA antibody (SorLA ab) alters the resistance of breast cancer cells to HER2 monoclonal antibody trastuzumab in vitro and in ovo. We found that SorLA ab and trastuzumab combination therapy also inhibits tumor cell proliferation and tumor cell density in a mouse xenograft model of HER2-positive breast cancer. In addition, SorLA ab inhibits the proliferation of breast cancer patient-derived explant three-dimensional cultures. These results provide, for the first time, proof of principle that SorLA is a druggable target in breast cancer

Combinatorial immunotherapies overcome MYC-driven immune evasion in triple negative breast cancer

Few patients with triple negative breast cancer (TNBC) benefit from immune checkpoint inhibitors with complete and durable remissions being quite rare. Oncogenes can regulate tumor immune infiltration, however whether oncogenes dictate diminished response to immunotherapy and whether these effects are reversible remains poorly understood. Here, we report that TNBCs with elevated MYC expression are resistant to immune checkpoint inhibitor therapy. Using mouse models and patient data, we show that MYC signaling is associated with low tumor cell PD-L1, low overall immune cell infiltration, and low tumor cell MHC-I expression. Restoring interferon signaling in the tumor increases MHC-I expression. By combining a TLR9 agonist and an agonistic antibody against OX40 with anti-PD-L1, mice experience tumor regression and are protected from new TNBC tumor outgrowth. Our findings demonstrate that MYC-dependent immune evasion is reversible and druggable, and when strategically targeted, may improve outcomes for patients treated with immune checkpoint inhibitors. The oncoprotein c-Myc is often overexpressed in triple negative breast cancer and has a role in tumor progression and resistance to therapy. Here the authors show that elevated MYC expression is correlated with low immune infiltration, diminished MHC-I pathway expression and that CpG/aOX40 treatment could overcome resistance to PD-L1 blockade in MYC-high breast tumors.Peer reviewe

Pharmacological reactivation of MYC-dependent apoptosis induces susceptibility to anti-PD-1 immunotherapy

Correction: Volume: 10 Article Number: 932 DOI: 10.1038/s41467-019-08956-x Published: FEB 20 2019 Accession Number: WOS:000459099300001Elevated MYC expression sensitizes tumor cells to apoptosis but the therapeutic potential of this mechanism remains unclear. We find, in a model of MYC-driven breast cancer, that pharmacological activation of AMPK strongly synergizes with BCL-2/BCL-X-L inhibitors to activate apoptosis. We demonstrate the translational potential of an AMPK and BCL-2/BCL-X-L co-targeting strategy in ex vivo and in vivo models of MYC-high breast cancer. Metformin combined with navitoclax or venetoclax efficiently inhibited tumor growth, conferred survival benefits and induced tumor infiltration by immune cells. However, withdrawal of the drugs allowed tumor re-growth with presentation of PD-1+/CD8+ T cell infiltrates, suggesting immune escape. A two-step treatment regimen, beginning with neoadjuvant metformin+venetoclax to induce apoptosis and followed by adjuvant metformin+venetoclax+anti-PD-1 treatment to overcome immune escape, led to durable antitumor responses even after drug withdrawal. We demonstrate that pharmacological reactivation of MYC-dependent apoptosis is a powerful antitumor strategy involving both tumor cell depletion and immunosurveillance.Peer reviewe

"Kotiin kun jalat kantaa" : Päihteiden käytön puheeksioton edistäminen Malmin ja Haartmanin yhteispäivystyksissä

Tutkimuksen tarkoituksena oli kuvata päihteiden käytön puheeksioton toteutumista Malmin ja Haartmanin yhteispäivystyksissä hoitohenkilökunnan kokemana sekä selvittää millä toimenpiteillä puheeksiottoa voitaisiin edistää ja helpottaa kyseisissä työyksiköissä. Tutkimuksen tavoitteena oli tuottaa tietoa siitä, mikä on päihteiden käytön puheeksioton tilanne keväällä 2019 sekä löytää keinoja, joita voidaan hyödyntää yhteispäivystysten päihdehoitotyön kehittämisessä puheeksioton edistämiseksi. Kvantitatiivisen tutkimuksen aineistonkeruumenetelmänä oli sähköinen Webropol-kysely. Kysely toteutettiin 8.-26.5.2019 välisenä aikana. Tutkimukseen osallistui kahdesta organisaatiosta yhteensä 75 hoitajaa (n= 42 ja n= 33). Tutkimuksen keskeiset tulokset esitettiin taulukoin, kuvioin ja tekstinä. Tutkimuksen tulokset vahvistivat tutkijoilla jo ennalta ollutta käsitystä puheeksioton haasteista ja toteutumisesta yhteispäivystyksissä. Näitä olivat kiireinen työympäristö, päihdepotilaiden kuormittavuus sekä hoitajien perehdytyksen puute puheeksiottoon ja riittämättömät resurssit sen toteuttamiseen. Nämä asiat korostuivat myös kyselyn vastauksissa. Yleisimmin päihteiden käytön puheeksiotto jäi toteutumatta ajan ja resurssien puutteen vuoksi. Erityisesti varhainen tunnistaminen vaikutti toteutuvan yhteispäivystyksissä huonosti. Puheeksiotto oli todennäköisempää, mikäli päihdeongelma oli selkeästi havaittavissa. Tulokset olivat samansuuntaisia kuin aiheesta aiemmin tehdyt kotimaiset ja kansainväliset tutkimukset. Päivystyksessä työskentelevien tulisi jatkossa nähdä itsensä voimakkaammin terveyden edistäjinä. Tämä vaatii jatkuvaa ja systemaattista henkilöstön koulutusta, jotta puheeksiotosta tulee rutiinia ja päihteitä käyttävien potilaiden kohtaaminen on mahdollisimman yhdenmukaista