Browsing by Subject "PATHWAYS"

Sort by: Order: Results:

Now showing items 1-20 of 66
  • Chen, Qiuzhen; Knickel, Karlheinz; Tesfai, Mehreteab; Sumelius, John; Turinawe, Alice; Isoto, Rosemary; Medyna, Galyna (2021)
    An important goal across Sub-Saharan Africa (SSA), and globally, is to foster a healthy nutrition. A strengthening of the diversity, sustainability, resilience and connectivity of food systems is increasingly seen as a key leverage point. Governance arrangements play a central role in connecting sustainable, resilient farming with healthy nutrition. In this article, we elaborate a framework for assessing, monitoring and improving the governance of food systems. Our focus is on food chains in six peri-urban and urban regions in SSA. A literature review on food chain governance and a mapping of current agri-food chains in the six regions provide the basis for the elaboration of an indicator-based assessment framework. The framework is adapted to the specific conditions of SSA and related goals. The assessment framework is then used to identify the challenges and opportunities in food chain governance in the six regions. The first testing of the framework indicates that the approach can help to identify disconnects, conflicting goals and tensions in food systems, and to formulate strategies for empowering agri-food chain actors in transitioning toward more efficient, equitable and sustainable agri-food systems. The article is concluded with a brief reflection on the strengths and weaknesses of the framework and suggests further testing and refinement.
  • Holster, Savanne; Hooiveld, Guido J.; Repsilber, Dirk; de Vos, Willem M.; Brummer, Robert J.; König, Julia (2019)
    Faecal microbiota transfer (FMT) consists of the introduction of new microbial communities into the intestine of a patient, with the aim of restoring a disturbed gut microbiota. Even though it is used as a potential treatment for various diseases, it is unknown how the host mucosa responds to FMT. This study aims to investigate the colonic mucosa gene expression response to allogenic (from a donor) or autologous (own) FMT in patients with irritable bowel syndrome (IBS). In a recently conducted randomised, double-blinded, controlled clinical study, 17 IBS patients were treated with FMT by colonoscopy. RNA was isolated from colonic biopsies collected by sigmoidoscopy at baseline, as well as two weeks and eight weeks after FMT. In patients treated with allogenic FMT, predominantly immune response-related gene sets were induced, with the strongest response two weeks after the FMT. In patients treated with autologous FMT, predominantly metabolism-related gene sets were affected. Furthermore, several microbiota genera showed correlations with immune-related gene sets, with different correlations found after allogenic compared to autologous FMT. This study shows that the microbe-host response is influenced by FMT on the mucosal gene expression level, and that there are clear differences in response to allogenic compared to autologous FMT.
  • Haider, Zahra; Larsson, Pär; Landfors, Mattias; Köhn, Linda; Schmiegelow, Kjeld; Flægstad, Trond; Kanerva, Jukka; Heyman, Mats; Hultdin, Magnus; Degerman, Sofie (2019)
    Classification of pediatric T-cell acute lymphoblastic leukemia (T-ALL) patients into CIMP (CpG Island Methylator Phenotype) subgroups has the potential to improve current risk stratification. To investigate the biology behind these CIMP subgroups, diagnostic samples from Nordic pediatric T-ALL patients were characterized by genome-wide methylation arrays, followed by targeted exome sequencing, telomere length measurement, and RNA sequencing. The CIMP subgroups did not correlate significantly with variations in epigenetic regulators. However, the CIMP+ subgroup, associated with better prognosis, showed indicators of longer replicative history, including shorter telomere length (P = 0.015) and older epigenetic (P <0.001) and mitotic age (P <0.001). Moreover, the CIMP+ subgroup had significantly higher expression of ANTP homeobox oncogenes, namely TLX3, HOXA9, HOXA10, and NKX2-1, and novel genes in T-ALL biology including PLCB4, PLXND1, and MYO18B. The CIMP- subgroup, with worse prognosis, was associated with higher expression of TAL1 along with frequent STIL-TAL1 fusions (2/40 in CIMP+ vs 11/24 in CIMP-), as well as stronger expression of BEX1. Altogether, our findings suggest different routes for leukemogenic transformation in the T-ALL CIMP subgroups, indicated by different replicative histories and distinct methylomic and transcriptomic profiles. These novel findings can lead to new therapeutic strategies.
  • Kortesoja, Laura; Vainikainen, Mari-Pauliina; Hotulainen, Risto; Rimpelä, Arja; Dobewall, Henrik; Lindfors, Pirjo; Karvonen, Sakari; Merikanto, Ilona (2020)
    The long-term effects of sleep on adolescent psychosocial well-being are mostly unknown, although insufficient sleep has been associated with emotional and behavioral difficulties in cross-sectional studies. With a five-year follow-up of Finnish adolescents (Time 1: n = 8834; Mean age = 13 years, 51.1% female, Time 2: n = 5315, Mean age = 15 years, 51.6% female, Time 3: n = 3712; Mean age = 17 years; 50.2% female), the purpose of this longitudinal study was to investigate the relations between self-reported sleep duration, sleep problems, and emotional and behavioral difficulties during adolescence. Emotional and behavioral difficulties were assessed using The Strengths and Difficulties Questionnaire (SDQ) measuring emotional symptoms, conduct problems, hyperactivity, peer problems and total difficulties. Sleep duration was calculated by counting the hours between self-reported bedtime and wake-up time. Sleep problems were assessed with a single question about the general sleep problems. According to the cross-lagged models for sleep and emotional and behavioral difficulties, the findings of this study indicate a developmental process during adolescence where, firstly, short sleep duration is a stronger predictor for current and prospective emotional and behavioral difficulties than vice versa. Secondly, increased emotional and behavioral difficulties expose adolescents to current and later sleep problems more strongly than reverse. Thus, the results show that short sleep duration predisposed to emotional and behavioral difficulties across adolescence, which then led to more prospective sleep problems. These findings suggest a developmental process where sleep and emotional and behavioral difficulties are intertwined in shaping adolescents' health.
  • Manninen, Atte A.; Gardberg, Maria; Juteau, Susanna; Ilmonen, Suvi; Jukonen, Joonas; Andersson, Noora; Carpen, Olli (2019)
    Background Sentinel node biopsy (SNB) is an important step in melanoma staging and prognostication. It is commonly performed for patients with intermediate thickness melanomas, based on clinicopathological features. However, only 20-25% of patients eventually demonstrate nodal involvement. The aim of this study was to evaluate whether tissue biomarkers with links to melanoma biology, together with clinicopathological parameters, could aid in the prediction of sentinel node involvement and improve selection of patients for SNB. In addition, we examined the role of these clinical or biological markers in disease outcome. Methods We collected a case-control cohort of 140 intermediate thickness (Breslow 0,9-4,0mm) melanoma patients with or without SNB involvement matched for age, gender, Breslow thickness and location. From this cohort, we tested the predictive value of common clinicopathological parameters (ulceration, mitotic count and tumor regression) and FMNL-2, ezrin and BRAF V600E immunoreactivity, for sentinel node involvement and survival. We further analyzed the correlations in the superficial spreading melanoma subtype. Results Based on our case control analysis, of the markers, BRAF V600E status (p = 0.010) and mitotic count (p = 0.036) correlated with SNB involvement. SNB status was a strong independent prognosticator for recurrence free survival (RFS p Conclusions These results demonstrate that BRAF immunohistochemistry could serve as a useful addition to a marker panel for selecting intermediate thickness melanoma patients for SNB.
  • Cadilhac, Dominique A.; Dewey, Helen M.; Denisenko, Sonia; Bladin, Christopher F.; Meretoja, Atte (2019)
    BackgroundHospital costs for stroke are increasing and variability in care quality creates inefficiencies. In 2007, the Victorian Government (Australia) employed clinical facilitators for three years in eight public hospitals to improve stroke care. Literature on the cost implications of such roles is rare. We report changes in the costs of acute stroke care following implementation of this program.MethodsObservational controlled before-and-after cohort design. Standardised hospital costing data were compared pre-program (financial year 2006-07) and post-program (2010-11) for all admitted episodes of stroke or transient ischaemic attack (TIA) using ICD-10 discharge codes. Costs in Australian dollars (AUD) were adjusted to a common year 2010. Generalised linear regression models were used for adjusted comparisons.ResultsA 20% increase in stroke and TIA episodes was observed: 2624 pre-program (age>75years: 53%) and 3142 post-program (age>75years: 51%); largely explained by more TIA admissions (up from 785 to 1072). Average length of stay reduced by 22% (pre-program 7.3days to post-program 5.7days, p
  • Koivisto, Elina; Acosta, Alicia Jurado; Moilanen, Anne-Mari; Tokola, Heikki; Aro, Jani; Pennanen, Harri; Sakkinen, Hanna; Kaikkonen, Leena; Ruskoaho, Heikki; Rysa, Jaana (2014)
  • Landreau, Armand; Juhola, Sirkku; Jurgilevich, Alexandra; Räsänen, Aleksi (2021)
    The assessments of future climate risks are common; however, usually, they focus on climate projections without considering social changes. We project heat risks for Finland to evaluate (1) what kind of differences there are in heat vulnerability projections with different scenarios and scales, and (2) how the use of socio-economic scenarios influences heat risk assessments. We project a vulnerability index with seven indicators downscaled to the postal code area scale for 2050. Three different scenario sets for vulnerability are tested: one with five global Shared Socioeconomic Pathways (SSPs) scenarios; the second with three European SSPs (EUSSPs) with data at the sub-national scale (NUTS2); and the last with the EUSSPs but aggregated data at the national scale. We construct projections of heat risk utilizing climatic heat hazard data for three different Representative Concentration Pathways (RCPs) and vulnerability and exposure data for five global SSPs up to 2100. In the vulnerability projections, each scenario in each dataset shows a decrease in vulnerability compared to current values, and the differences between the three scenario sets are small. There are evident differences both in the spatial patterns and in the temporal trends when comparing the risk projections with constant vulnerability to the projections with dynamic vulnerability. Heat hazard increases notably in RCP4.5 and RCP8.5, but a decrease of vulnerability especially in SSP1 and SSP5 alleviates risks. We show that projections of vulnerability have a considerable impact on future heat-related risk and emphasize that future risk assessments should include the combination of long-term climatic and socio-economic projections.
  • Pitkanen, Esa; Jouhten, Paula; Hou, Jian; Syed, Muhammad Fahad; Blomberg, Peter; Kludas, Jana; Oja, Merja; Holm, Liisa; Penttila, Merja; Rousu, Juho; Arvas, Mikko (2014)
  • Hajkarim, Morteza Chalabi; Karjalainen, Ella; Osipovitch, Mikhail; Dimopoulos, Konstantinos; Gordon, Sandra L.; Ambri, Francesca; Rasmussen, Kasper Dindler; Gronbaek, Kirsten; Helin, Kristian; Wennerberg, Krister; Won, Kyoung-Jae (2022)
    Large-scale multiparameter screening has become increasingly feasible and straightforward to perform thanks to developments in technologies such as high-content microscopy and high-throughput flow cytometry. The automated toolkits for analyzing similarities and differences between large numbers of tested conditions have not kept pace with these technological developments. Thus, effective analysis of multiparameter screening datasets becomes a bottleneck and a limiting factor in unbiased interpretation of results. Here we introduce compaRe, a toolkit for large-scale multiparameter data analysis, which integrates quality control, data bias correction, and data visualization methods with a mass-aware gridding algorithm-based similarity analysis providing a much faster and more robust analyses than existing methods. Using mass and flow cytometry data from acute myeloid leukemia and myelodysplastic syndrome patients, we show that compaRe can reveal interpatient heterogeneity and recognizable phenotypic profiles. By applying compaRe to high-throughput flow cytometry drug response data in AML models, we robustly identified multiple types of both deep and subtle phenotypic response patterns, highlighting how this analysis could be used for therapeutic discoveries. In conclusion, compaRe is a toolkit that uniquely allows for automated, rapid, and precise comparisons of large-scale multiparameter datasets, including high-throughput screens.
  • Karinen, Sirkku; Heikkinen, Tuomas; Nevanlinna, Heli; Hautaniemi, Sampsa (2011)
  • van Dongen, Katja C. W.; Linkens, Armand M. A.; Wetzels, Suzan M. W.; Wouters, Kristiaan; Vanmierlo, Tim; van de Waarenburg, Marjo P. H.; Scheijen, Jean L. J. M.; de Vos, Willem M.; Belzer, Clara; Schalkwijk, Casper G. (2021)
    Scope: Dietary advanced glycation endproducts (AGEs) are associated with negative biological effects, possibly due to accumulation in plasma and tissues and through modulation of inflammation and gut microbiota. Whether these biological consequences are reversible by limiting dietary AGE intake is unknown. Methods and results: Young healthy C57BL/6 mice were fed a standard chow (n = 10) or a baked chow high AGE-diet (n = 10) (~1.8–6.9 fold increased protein-bound Nε-(carboxymethyl)lysine (CML), Nε-(1-carboxyethyl) lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1)) for 10 weeks or a switch diet with baked chow for 5 weeks followed by 5 weeks of standard chow (n = 10). We assessed accumulation of AGEs in plasma, kidney, and liver and measured inflammatory markers and gut microbial composition. After 10 weeks of baked chow, a substantial panel of AGEs were increased in plasma, liver, and kidney. These increases were normalized after the switch diet. The inflammatory z-score increased after the baked chow diet. Gut microbial composition differed significantly between groups, with enriched Dubosiella spp. dominating these alterations. Conclusion: A high AGE-diet led to an increase of AGEs in plasma, kidney, and liver and to more inflammation and modification of the gut microbiota. These effects were reversed or discontinued by a diet lower in AGEs.
  • Kallankari, Hanna; Saunavaara, Virva; Parkkola, Riitta; Haataja, Leena; Hallman, Mikko; Kaukola, Tuula (2021)
    Background Very preterm birth can disturb brain maturation and subject these high-risk children to neurocognitive difficulties later. Objective The aim of the study was to evaluate the impact of prematurity on microstructure of frontostriatal tracts in children with no severe neurologic impairment, and to study whether the diffusion tensor imaging metrics of frontostriatal tracts correlate to executive functioning. Materials and methods The prospective cohort study comprised 54 very preterm children (mean gestational age 28.8 weeks) and 20 age- and gender-matched term children. None of the children had severe neurologic impairment. The children underwent diffusion tensor imaging and neuropsychological assessments at a mean age of 9 years. We measured quantitative diffusion tensor imaging metrics of frontostriatal tracts using probabilistic tractography. We also administered five subtests from the Developmental Neuropsychological Assessment, Second Edition, to evaluate executive functioning. Results Very preterm children had significantly higher fractional anisotropy and axial diffusivity values (P
  • Bousquet, Jean; Anto, Josep M.; Haahtela, Tari; Jousilahti, Pekka; Erhola, Marina; Basagana, Xavier; Czarlewski, Wienczyslawa; Odemyr, Mikaela; Palkonen, Susanna; Sofiev, Mikael; Velasco, Cesar; Bedbrook, Anna; Delgado, Rodrigo; Kouznetsov, Rostislav; Mäkelä, Mika; Palamarchuk, Yuliia; Saarinen, Kimmo; Tommila, Erja; Valovirta, Erkka; Vasankari, Tuula; Zuberbier, Torsten; Annesi-Maesano, Isabella; Benveniste, Samuel; Mathieu-Dupas, Eve; Pepin, Jean-Louis; Picard, Robert; Zeng, Stephane; Ayache, Julia; Calves Venturos, Nuria; Micheli, Yann; Jullian-Desayes, Ingrid; Laune, Daniel (2020)
    In December 2019, a conference entitled "Europe That Protects: Safeguarding Our Planet, Safeguarding Our Health" was held in Helsinki. It was co-organized by the Finnish Institute for Health and Welfare, the Finnish Environment Institute and the European Commission, under the auspices of Finland's Presidency of the EU. As a side event, a symposium organized as the final POLLAR (Impact of air POLLution on Asthma and Rhinitis) meeting explored the digital transformation of health and care to sustain planetary health in airway diseases. The Finnish Allergy Programme collaborates with MASK (Mobile Airways Sentinel NetworK) and can be considered as a proof-of-concept to impact Planetary Health. The Good Practice of DG Sante (The Directorate-General for Health and Food Safety) on digitally-enabled, patient-centred care pathways is in line with the objectives of the Finnish Allergy Programme. The ARIACARE-Digital network has been deployed in 25 countries. It represents an example of the digital cross-border exchange of real-world data and experience with the aim to improve patient care. The integration of information technology tools for climate, weather, air pollution and aerobiology in mobile Health applications will enable the development of an alert system. Citizens will thus be informed about personal environmental threats, which may also be linked to indicators of Planetary Health and sustainability. The digital transformation of the public health policy was also proposed, following the experience of the Agency for Health Quality and Assessment of Catalonia (AQuAS).
  • Jämsen, Eemeli; Pajarinen, Jukka; Lin, Tzu-hua; Lo, Chi-Wen; Nabeshima, Akira; Lu, Laura; Nathan, Karthik; Eklund, Kari K.; Yao, Zhenyu; Goodman, Stuart B. (2020)
    Macrophage-mediated inflammatory reaction to implant wear particles drives bone loss around total joint replacements (TJR). Although most TJR recipients are elderly, studies linking wear particle-activated macrophages and peri-implant osteolysis have not taken into account the multiple effects that aging has on the innate immune system and, in particular, on macrophages. To address this, we compared the wear particle responses of bone marrow macrophages obtained from young (2-month) and aged (18-month) mice. Macrophages were polarized to M0, M1, or M2 phenotypes in vitro, challenged with titanium particles, and their inflammatory response was characterized at multiple time points by quantitative reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay. In addition, age-dependent changes in activation of transcription factor nuclear factor-kappa B were analyzed by a lentiviral vector-based luciferase reporter system. The particle stimulation experiment was further repeated using human primary macrophages isolated from blood donors of different ages. We found that the pro-inflammatory responses were generally higher in macrophages obtained from young mice, but differences between the age groups remained small and of uncertain biological significance. Noteworthily, M2 polarization effectively suppressed the particle-induced inflammation in both young and aged macrophages. These results suggest that aging of the innate immune system per se plays no significant role in the response of macrophages to titanium particles, whereas induction of M2 polarization appears a promising strategy to limit macrophage-mediated inflammation regardless of age.
  • Anwar, Tahira; Liu, Xiaonan; Suntio, Taina; Marjamäki, Annika; Biazik, Joanna; Chan, Edmond Y. W.; Varjosalo, Markku; Eskelinen, Eeva-Liisa (2019)
    Autophagy transports cytoplasmic material and organelles to lysosomes for degradation and recycling. Beclin 1 forms a complex with several other autophagy proteins and functions in the initiation phase of autophagy, but the exact role of Beclin 1 subcellular localization in autophagy initiation is still unclear. In order to elucidate the role of Beclin 1 localization in autophagosome biogenesis, we generated constructs that target Beclin 1 to the endoplasmic reticulum (ER) or mitochondria. Our results confirmed the proper organelle-specific targeting of the engineered Beclin 1 constructs, and the proper formation of autophagy-regulatory Beclin 1 complexes. The ULK kinases are required for autophagy initiation upstream of Beclin 1, and autophagosome biogenesis is severely impaired in ULK1/ULK2 double knockout cells. We tested whether Beclin 1 targeting facilitated its ability to rescue autophagosome formation in ULK1/ULK2 double knockout cells. ER-targeted Beclin 1 was most effective in the rescue experiments, while mitochondria-targeted and non-targeted Beclin 1 also showed an ability to rescue, but with lower activity. However, none of the constructs was able to increase autophagic flux in the knockout cells. We also showed that wild type Beclin 1 was enriched on the ER during autophagy induction, and that ULK1/ULK2 facilitated the ER-enrichment of Beclin 1 under basal conditions. The results suggest that one of the functions of ULK kinases may be to enhance Beclin 1 recruitment to the ER to drive autophagosome formation.
  • Voutilainen, Silja H.; Kosola, Silja K.; Lohi, Jouko; Jahnukainen, Timo; Pakarinen, Mikko P.; Jalanko, Hannu J (2021)
    Background Unexplained graft fibrosis and inflammation are common after pediatric liver transplantation (LT). Objective We investigated the graft expression of fibrogenic genes and correlated the findings with transplant histopathology and outcome. Methods Liver biopsies from 29 recipients were obtained at a median of 13.1 (IQR: 5.0-18.4) years after pediatric LT. Control samples were from six liver-healthy subjects. Hepatic expression of 40 fibrosis-related genes was correlated to histological findings: normal histology, fibrosis with no inflammation, and fibrosis with inflammation. Liver function was evaluated after a subsequent follow-up of 9.0 years (IQR: 8.0-9.4). Results Patients with fibrosis and no inflammation had significantly increased gene expression of profibrotic TGF-beta 3 (1.17 vs. 1.02 p = .005), CTGF (1.64 vs. 0.66 p = .014), PDGF-alpha (1.79 vs. 0.98 p = .049), PDGF -beta (0.99 vs. 0.76 p = .006), integrin-subunit-beta 1 (1.19 vs. 1.02 p = .045), alpha-SMA (1.12 vs. 0.58 p = .013), type I collagen (0.82 vs. 0.53 p = .005) and antifibrotic decorin (1.15 vs. 0.99 p = .045) compared to patients with normal histology. mRNA expression of VEGF A (0.84 vs. 1.06 p = .049) was lower. Only a few of the studied genes were upregulated in patients with both fibrosis and inflammation. The gene expression levels showed no association with later graft outcome. Conclusions Altered hepatic expression of fibrosis-related genes is associated with graft fibrosis without concurrent inflammation.
  • Kujala, Susanna; Hakala, Outi; Viitaharju, Leena (2022)
    Organic farming is recognised as a potential approach to achieve a more sustainable food system and promote rural development. Thus, many countries have set targets to increase the share of organic cultivated land. In Finland, the target was to increase the share of organic farming to 20% of the total area under cultivation by 2020. Although the share of organic agricultural land has gradually increased, there are still significant regional differences. The aim of our study is to identify the factors that affect these differences. Previous research has generally excluded factors such as subsidies from the analysis; therefore, this study explores the relevance of subsidies, as well as other key factors, within the context of the uneven regional distribution of organic farming in Finland. The data sources include research from the literature, official statistics, and a large survey of organic farmers. Using qualitative comparative analysis (QCA), we identify three different pathways that have led to higher organic shares of agricultural land in certain Finnish regions. The three regions with the highest organic shares utilise the first pathway, which includes a long organic heritage, a focus on dairy farming, and an important reliance on subsidies. We conclude that the regional variation in organic farming in Finland is due to a combination of different factors, rather than any single factor. Moreover, subsidies are a key factor that should be considered when reviewing the reasons for regional variations in organic farming.
  • Hoornstra, Douwe; Vesterlin, Jenni; Parnanen, Pirjo; Al-Samadi, Ahmed; Zlotogorski-Hurvitz, Ayelet; Vered, Marilena; Salo, Tuula (2018)
    Background: Oral tongue squamous cell carcinoma (OTSCC) cells are highly proliferative and invasive. Lingonberry contains several polyphenolic compounds similar to curcumin. We hypothesize that fermented lingonberry juice (FLJ) has an anti-invasive and anti-proliferative effect on OTSCC cells similarly to curcumin, which is known to be anti-carcinogenic. Materials and Methods: FLJ, curcumin dissolved in ethanol, or curcumin loaded in Candida extracellular vesicles (EVs) were added to more (HSC-3) and less aggressive (SCC-25) OTSCC cells. Cell proliferation was measured with a 5-bromo-2'-deoxyuridine kit and invasion in the three-dimensional Myogel spheroid assay. Statistical analyses were completed with one-way ANOVA and Bonferroni post-hoc testing. Results: Both FLJ and curcumin significantly reduced the proliferation and invasion of HSC-3 and SCC-25 cells. The effects of curcumin were not improved when cells were treated with curcumin loaded within EVs. Conclusion: Our results suggest that FLJ, like curcumin, has an anti-carcinogenic effect on aggressive OTSCC cells in vitro.
  • Haapa-Paananen, Saija; Chen, Ping; Hellström, Kirsi; Kohonen, Pekka; Hautaniemi, Sampsa; Kallioniemi, Olli; Perala, Merja (2013)