Articles from BioMed Central

 

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  • Hirvonen, Elina A M; Pitkänen, Esa; Hemminki, Kari; Aaltonen, Lauri A; Kilpivaara, Outi (BioMed Central, 2017)
    Abstract Background Polycythemia vera (PV), characterized by massive production of erythrocytes, is one of the myeloproliferative neoplasms. Most patients carry a somatic gain-of-function mutation in JAK2, c.1849G > T (p.Val617Phe), leading to constitutive activation of JAK-STAT signaling pathway. Familial clustering is also observed occasionally, but high-penetrance predisposition genes to PV have remained unidentified. Results We studied the predisposition to PV by exome sequencing (three cases) in a Finnish PV family with four patients. The 12 shared variants (maximum allowed minor allele frequency <0.001 in Finnish population in ExAC database) predicted damaging in silico and absent in an additional control set of over 500 Finns were further validated by Sanger sequencing in a fourth affected family member. Three novel predisposition candidate variants were identified: c.1254C > G (p.Phe418Leu) in ZXDC, c.1931C > G (p.Pro644Arg) in ATN1, and c.701G > A (p.Arg234Gln) in LRRC3. We also observed a rare, predicted benign germline variant c.2912C > G (p.Ala971Gly) in BCORL1 in all four patients. Somatic mutations in BCORL1 have been reported in myeloid malignancies. We further screened the variants in eight PV patients in six other Finnish families, but no other carriers were found. Conclusions Exome sequencing provides a powerful tool for the identification of novel variants, and understanding the familial predisposition of diseases. This is the first report on Finnish familial PV cases, and we identified three novel candidate variants that may predispose to the disease.
  • Tegelberg, Saara; Tomašić, Nikica; Kallijärvi, Jukka; Purhonen, Janne; Elmér, Eskil; Lindberg, Eva; Nord, David G; Soller, Maria; Lesko, Nicole; Wedell, Anna; Bruhn, Helene; Freyer, Christoph; Stranneheim, Henrik; Wibom, Rolf; Nennesmo, Inger; Wredenberg, Anna; Eklund, Erik A; Fellman, Vineta (BioMed Central, 2017)
    Abstract Background Mitochondrial diseases due to defective respiratory chain complex III (CIII) are relatively uncommon. The assembly of the eleven-subunit CIII is completed by the insertion of the Rieske iron-sulfur protein, a process for which BCS1L protein is indispensable. Mutations in the BCS1L gene constitute the most common diagnosed cause of CIII deficiency, and the phenotypic spectrum arising from mutations in this gene is wide. Results A case of CIII deficiency was investigated in depth to assess respiratory chain function and assembly, and brain, skeletal muscle and liver histology. Exome sequencing was performed to search for the causative mutation(s). The patient’s platelets and muscle mitochondria showed respiration defects and defective assembly of CIII was detected in fibroblast mitochondria. The patient was compound heterozygous for two novel mutations in BCS1L, c.306A > T and c.399delA. In the cerebral cortex a specific pattern of astrogliosis and widespread loss of microglia was observed. Further analysis showed loss of Kupffer cells in the liver. These changes were not found in infants suffering from GRACILE syndrome, the most severe BCS1L-related disorder causing early postnatal mortality, but were partially corroborated in a knock-in mouse model of BCS1L deficiency. Conclusions We describe two novel compound heterozygous mutations in BCS1L causing CIII deficiency. The pathogenicity of one of the mutations was unexpected and points to the importance of combining next generation sequencing with a biochemical approach when investigating these patients. We further show novel manifestations in brain, skeletal muscle and liver, including abnormality in specialized resident macrophages (microglia and Kupffer cells). These novel phenotypes forward our understanding of CIII deficiencies caused by BCS1L mutations.
  • Hiitiö, Heidi; Vakkamäki, Johanna; Simojoki, Heli; Autio, Tiina; Junnila, Jouni; Pelkonen, Sinikka; Pyörälä, Satu (BioMed Central, 2017)
    Abstract Background The dairy industry has undergone substantial structural changes as intensive farming has developed during recent decades. Mastitis continues to be the most common production disease of dairy cows. Nationwide surveys of mastitis prevalence are useful in monitoring udder health of dairy herds and to study the impact of structural changes on the dairy industry. This survey on bovine subclinical mastitis was the first based on cow composite milk somatic cell count (SCC) data from the Finnish national health monitoring and milk recording database. A cow with composite milk SCC ≥200,000 cells/ml in at least one of the four test milkings during the year was considered to have subclinical mastitis and a cow with composite milk SCC ≥200,000 cells/ml in three or in all four test milkings during the year to have chronic subclinical mastitis. The aim of the study was to determine the prevalence of subclinical mastitis and chronic subclinical mastitis in Finland in 1991, 2001 and 2010 and to investigate cow and herd factors associated with elevated SCC. Results Prevalence of subclinical mastitis in Finland decreased over recent decades from 22.3% (1991) and 20.1% (2001) to 19.0% (2010). Prevalence of chronic subclinical mastitis was 20.4% in 1991, 15.5% in 2001 and 16.1% in 2010. The most significant cow and herd factors associated with subclinical mastitis or high milk SCC were increasing parity, Holstein breed, free-stalls with an automatic milking system and organic production. Milk SCC were highest from July to September. Main factors associated with chronic mastitis were increasing parity and Holstein breed. Conclusions Prevalence of subclinical mastitis in Finland decreased over recent decades, the greatest change taking place during the first decade of the study. Prevalence of chronic subclinical mastitis significantly decreased from 1991. The most significant factors associated with both types of mastitis were increasing parity and Holstein breed, and for subclinical mastitis also free-stalls with automatic milking. National surveys on mastitis prevalence should be carried out at regular intervals to monitor udder health of dairy cows and to study the impact of the ongoing structural changes in the dairy industry to enable interventions related to udder health to be made when needed.
  • Pawar, Prashant M; Derba-Maceluch, Marta; Chong, Sun-Li; Gandla, Madhavi L; Bashar, Shamrat S; Sparrman, Tobias; Ahvenainen, Patrik; Hedenström, Mattias; Özparpucu, Merve; Rüggeberg, Markus; Serimaa, Ritva; Lawoko, Martin; Tenkanen, Maija; Jönsson, Leif J; Mellerowicz, Ewa J (BioMed Central, 2017)
    Abstract Background Lignocellulose from fast growing hardwood species is a preferred source of polysaccharides for advanced biofuels and “green” chemicals. However, the extensive acetylation of hardwood xylan hinders lignocellulose saccharification by obstructing enzymatic xylan hydrolysis and causing inhibitory acetic acid concentrations during microbial sugar fermentation. To optimize lignocellulose for cost-effective saccharification and biofuel production, an acetyl xylan esterase AnAXE1 from Aspergillus niger was introduced into aspen and targeted to cell walls. Results AnAXE1-expressing plants exhibited reduced xylan acetylation and grew normally. Without pretreatment, their lignocellulose yielded over 25% more glucose per unit mass of wood (dry weight) than wild-type plants. Glucose yields were less improved (+7%) after acid pretreatment, which hydrolyses xylan. The results indicate that AnAXE1 expression also reduced the molecular weight of xylan, and xylan–lignin complexes and/or lignin co-extracted with xylan, increased cellulose crystallinity, altered the lignin composition, reducing its syringyl to guaiacyl ratio, and increased lignin solubility in dioxane and hot water. Lignin-associated carbohydrates became enriched in xylose residues, indicating a higher content of xylo-oligosaccharides. Conclusions This work revealed several changes in plant cell walls caused by deacetylation of xylan. We propose that deacetylated xylan is partially hydrolyzed in the cell walls, liberating xylo-oligosaccharides and their associated lignin oligomers from the cell wall network. Deacetylating xylan thus not only increases its susceptibility to hydrolytic enzymes during saccharification but also changes the cell wall architecture, increasing the extractability of lignin and xylan and facilitating saccharification.
  • Mikkonen, Susanna; Pylväs, Laura; Rintala, Heta; Nokelainen, Petri; Postareff, Liisa (Springer International Publishing, 2017)
    Abstract This review provides an overview of the empirical research concerning guidance in the context of vocational education and training (VET). The study examines practices, providers and supporting and hindering factors related to guidance and learning at the workplace. After the inclusion/exclusion process, the final number of research articles included in this review is 18. Results show strong evidence for the collective nature of workplace guidance, with the entire work community providing learners with guidance and assistance. Guidance provided to VET students at workplaces seems to relate strongly to the activities of the members of communities of practice. Guidance provided by the members of communities of practice opens up opportunities for learners to participate in collective practices by gradually assuming more responsibility and more demanding tasks as their skills develop. The learner’s self-regulative skills, such as responsibility and the ability to take the initiative and to actively seek guidance, affect how guidance is afforded to him/her in the work community during training. Furthermore, these skills may also determine the learner’s prospects for developing expertise in future workplaces.
  • Viranta, Suvi; Atickem, Anagaw; Werdelin, Lars; Stenseth, Nils C (BioMed Central, 2017)
    Abstract Background The African wolf, for which we herein recognise Canis lupaster Hemprich and Ehrenberg, 1832 (Symbolae Physicae quae ex Itinere Africam Borealem er Asoam Occidentalem Decas Secunda. Berlin, 1833) as the valid species name (we consider the older name Canis anthus Cuvier, 1820 [Le Chacal de Sénégal, Femelle. In: Geoffroy St.-Hilaire E, Cuvier F, editors. Histoire Naturelle des Mammifères Paris, A. Belin, 1820] a nomen dubium), is a medium-sized canid with wolf-like characters. Because of phenotypic similarity, specimens of African wolf have long been assigned to golden jackal (Canis aureus Linnaeus, 1758 [Systema Naturae per Regna Tria Naturae, Secundum Classes, Ordines, Genera, Species, cum Characteribus, Differentiis, Synonymis, Locis. Tomus I. Editio decima, reformata, 1758]). Results Here we provide, through rigorous morphological analysis, a species description for this taxonomically overlooked species. Through molecular sequencing we assess its distribution in Africa, which remains uncertain due to confusion regarding possible co-occurrence with the Eurasian golden jackal. Canis lupaster differs from all other Canis spp. including the golden jackal in its cranial morphology, while phylogenetically it shows close affinity to the Holarctic grey wolf (Canis lupus Linnaeus, 1758 [Systema Naturae per Regna Tria Naturae, Secundum Classes, Ordines, Genera, Species, cum Characteribus, Differentiis, Synonymis, Locis. Tomus I. Editio decima, reformata, 1758]). All sequences generated during this study clustered with African wolf specimens, consistent with previous data for the species. Conclusions We suggest that the estimated current geographic range of golden jackal in Africa represents the African wolf range. Further research is needed in eastern Egypt, where a hybrid zone between Eurasian golden jackal and African wolf may exist. Our results highlight the need for improved studies of geographic range and population surveys for the taxon, which is classified as ‘least concern’ by the IUCN due to its erroneous identification as golden jackal. As a species exclusively distributed in Africa, investigations of the biology and threats to African wolf are needed.
  • Vilmi-Kerälä, Tiina; Lauhio, Anneli; Tervahartiala, Taina; Palomäki, Outi; Uotila, Jukka; Sorsa, Timo; Palomäki, Ari (BioMed Central, 2017)
    Abstract Background Gestational diabetes mellitus (GDM) has significant implications for the future health of the mother. Some clinical studies have suggested subclinical inflammation and vascular dysfunction after GDM. We aimed to study whether concentrations of high-sensitivity C-reactive protein (hsCRP), tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-8 (MMP-8) and -9, as well as values of arterial stiffness differ between women with and without a history of GDM a few years after delivery. We also investigated possible effects of obesity on the results. Methods We studied two cohorts—120 women with a history of GDM and 120 controls—on average 3.7 years after delivery. Serum concentrations of hsCRP were determined by immunonephelometric and immunoturbidimetric methods, MMP-8 by immunofluorometric assay, and MMP-9 and TIMP-1 by enzyme-linked immunosorbent assays. Pulse wave velocity (PWV) was determined using the foot-to-foot velocity method from carotid and femoral waveforms by using a SphygmoCor device. Arterial compliance was measured non-invasively by an HDI/PulseWave™CR-2000 arterial tonometer. All 240 women were also included in subgroup analyses to study the effect of obesity on the results. Multiple linear regression analyses were performed with adjustment for confounding factors. Results PWV after pregnancy complicated by GDM was significantly higher than after normal pregnancy, 6.44 ± 0.83 (SD) vs. 6.17 ± 0.74 m/s (p = 0.009). Previous GDM was also one of the significant determinants of PWV in multiple linear regression analyses. On the other hand, compliance indices of both large (p = 0.092) and small (p = 0.681) arteries did not differ between the study cohorts. Serum TIMP-1 levels were significantly increased after previous GDM (p = 0.020). However, no differences were found in the serum levels of MMP-8, MMP-9 or hsCRP. In subgroup analyses, there were significantly higher concentrations of hsCRP (p = 0.015) and higher PWV (p < 0.001) among obese women compared with non-obese ones. Conclusions PWV values were significantly higher after GDM compared with normoglycemic pregnancies and were associated with prolonged TIMP-1 upregulation. Cardiovascular risk factors were more common in participants with high BMI than in those with previous GDM.
  • Patel, Kishan; Kouvonen, Anne; Close, Ciara; Väänänen, Ari; O’Reilly, Dermot; Donnelly, Michael (BioMed Central, 2017)
    Abstract Background Previous studies investigating the mental health of migrants have shown mixed results. The increased availability of register data has led to a growing number of register-based studies in this research area. This is the first scoping review on the use of registry and record-linkage data to examine the mental health of migrant populations. The aim of this scoping review is to investigate the topics covered and to assess the results yielded from these studies. Methods We used a scoping review methodology to search MedLine, PubMed, PsychINFO, Web of Science, and SCOPUS for all register-based studies on the mental health of migrants. Two reviewers screened all papers, independently, using iteratively applied inclusion and exclusion criteria. Using gradually broadening inclusion and exclusion criteria for maximum “scope,” newly published criteria developed to appraise the methodological quality of record-linkage studies were applied to eligible papers and data were extracted in a charting exercise. Results A total of 1309 papers were screened and appraised, 51 of which met the eligibility and quality criteria and were included in the review. This review identified four major domains of register-based research within the topic of migrant mental health: rates and risks of psychiatric disorders, rates and risks of suicide mortality, the use of psychotropic drugs, and health service utilisation and mental health-related hospitalisation rates. We found that whilst migrants can be at an increased risk of developing psychotic disorders and suicide mortality, they are less likely to use psychotropic medication and mental health-related services. Conclusions This review systematically charts the register-based studies on migrants’ mental health for the first time. It shows the main topics and gaps in knowledge in this research domain, discusses the disadvantages of register-based studies, and suggests new directions for forthcoming studies.
  • Kuuliala, Krista; Kuuliala, Antti; Koivuniemi, Riitta; Kautiainen, Hannu; Repo, Heikki; Leirisalo-Repo, Marjatta (BioMed Central, 2017)
    Abstract Background We found recently that baseline signal transducer and activator of transcription 3 phosphorylation in peripheral blood CD4+ T cells of patients with early rheumatoid arthritis (RA) is associated with treatment response to synthetic disease-modifying antirheumatic drugs (DMARDs). This prompted us to study the baseline phosphorylation profiles of Janus kinases (JAKs) in blood leukocytes with respect to treatment response in early RA. Methods Thirty-five DMARD-naïve patients with early RA provided blood samples for whole blood flow cytometric determination of phosphorylation of JAKs in CD4+ and CD8+ T cells, CD19+ B cells, and CD14+ monocytes. Treatment response was determined after 1 year of treatment with synthetic DMARDs, with remission defined as absence of tender and swollen joints and normal erythrocyte sedimentation rate. Exact logistic regression was used to investigate the association of baseline variables with treatment response. Ninety-five percent CIs of means were estimated by bias-corrected bootstrapping. Results High JAK3 phosphorylation in CD4+ and CD8+ T cells, CD19+ B cells, and CD14+ monocytes and low JAK2 phosphorylation in CD14+ monocytes were significantly associated with remission following treatment with synthetic DMARDs. Conclusions Baseline JAK phosphorylation profile in peripheral blood leukocytes may provide a means to predict treatment response achieved by synthetic DMARDs among patients with early RA.
  • Hirvonen, Katariina; Laivuori, Hannele; Lahti, Jari; Strandberg, Timo; Eriksson, Johan G; Hackman, Peter (BioMed Central, 2017)
    Abstract Background Sirtuin-6 (SIRT6) is involved in various crucial cellular pathways, being a key regulator of telomere structure, DNA repair, metabolism, transcriptional control and the NF-kappa B pathway. Sirt6 knock-out mice have been reported to develop typical features of aging and senescence at the age of 2–3 weeks and die within 4 weeks. The aim of this study was to investigate whether sequence variations of SIRT6 are associated with aging and longevity in Finnish men. Methods The sample of this study consisted of 43 longer-living and healthy males and 92 male control subjects who have died of natural causes at an average age of 66,6 (±4,1) years and who belonged to the Helsinki Birth Cohort Study (HBCS). Single nucleotide polymorphisms (SNPs) in the exons and their surroundings of the SIRT6 were studied using direct PCR sequencing. Results The SNP rs117385980 (C > T), situated 23 bases downstream of the exon 2 exon/intron border was found in heterozygous form in 1/43 longer-living healthy men (Minor allele frequency (MAF) 0,0116) and in 9/92 controls (MAF 0,0489). To replicate this finding, we studied a group of 63 healthy men at an average age of 83 years from the Helsinki Businessmen Study (HBS)–cohort. The heterozygosity of the same SNP was seen in 2/63 men from the HBS–cohort (MAF 0,0159). Fisher exact test was performed in our two combined study samples. The P-value for all samples combined was 0.07 and the odds ratio 3.53 (95% confidence interval 0.96–13.4). Conclusions These results suggest an inverse association between the T allele of rs117385980 and longevity. The result needs to be confirmed in a larger study. It remains to be determined whether rs117385980 itself has an effect or if it is a mere genetic marker for some other yet undiscovered sequence variant causing a functional effect.
  • Pouessel, Guillaume; Claverie, Claire; Labreuche, Julien; Renaudin, Jean-Marie; Dorkenoo, Aimée; Eb, Mireille; Moneret-Vautrin, Anne; Deschildre, Antoine; Leteurtre, Stephane; Grabenhenrich, Linus; Worm, Margitta; Dölle, Sabine; Scherer, Kathrin; Hutteger, Isidor; Christensen, Morten; Bindslev-Jensen, Carsten; Mortz, Charlotte; Eller, Esben; Kjaer, Henrik F; Carneiro-Leão, Leonor; Badas, Jenny; Coimbra, Alice; Levy, Dikla P; Ben-Shoshan, Moshe; Rimon, Ayelet; Benor, Shira; Arends, Nicolette J T; Edelbroek, Nikki; de Groot, Hans; Emons, Joyce A M; Brand, H. K A; Verhoeven, Dirk; van Veen, Leonieke N; de Jong, Nicolette W; Noh, Geunwoong; Jang, Eun H; Pascal, Mariona; Dominguez, Olga; Piquer, Mònica; Alvaro, Montserrat; Jimenez-Feijoo, Rosa; Lozano, Jaime; Machinena, Adriana; del Mar Folqué, Maria; Giner, Maria T; Plaza, Ana M; Turner, Paul; Patel, Nandinee; Vazquez-Ortiz, Marta; Lindsley, Sarah; Walker, Lucy; Rosenberg, Simon; Mari, Adriano; Alessandri, Claudia; Giangrieco, Ivana; Tuppo, Lisa; Rafaiani, Chiara; Mitterer, Georg; Ciancamerla, Michela; Ferrara, Rosetta; Bernardi, Maria L; Zennaro, Danila; Tamburrini, Maurizio; Ciardiello, Maria A; Harwanegg, Christian; Fernandez, Antonio; Selb, Regina; Egenmann, Philippe; Epstein, Michelle; Hoffmann-Sommergruber, Karin; Koning, Frits; Lovik, Martinus; Clare Mills, E. N; Moreno, Javier; van Loveren, Henk; Wal, Jean-Michel; Diesner, Susanne; Bergmayr, Cornelia; Pfitzner, Barbara; Assmann, Vera E; Starkl, Philipp; Endesfelder, David; Eiwegger, Thomas; Szepfalusi, Zsolt; Fehrenbach, Heinz; Jensen-Jarolim, Erika; Hartmann, Anton; Pali-Schöll, Isabella; Untersmayr, Eva; Wille, Soren; Meyer, Peter; Klingebiel, Caroline; Lidholm, Jonas; Ehrenberg, Angelica; Östling, Jonas; Cleach, Isabelle; Mège, Jean-Louis; Vitte, Joana; Aina, Roberta; Dubiela, Pawel; Pfeifer, Sabine; Bublin, Merima; Radauer, Christian; Humeniuk, Piotr; Kabasser, Stefan; Asero, Riccardo; Bogas, Gador; Gomez, Francisca; Campo, Paloma; Salas, Maria; Doña, Inmaculada; Barrionuevo, Esther; Guerrero, Maria A; Mayorga, Cristobalina; Prieto, Ana; Barber, Domingo; Torres, Maria J; Jamin, Annette; Wangorsch, Andrea; Ballmer, Barbara; Vieths, Stefan; Scheurer, Stephan; Apostolovic, Danijela; Mihailovic, Jelena; Krstic, Maja; Starkhammar, Maria; Velickovic, Tanja C; Hamsten, Carl; van Hage, Marianne; van Erp, Francine C; Knol, Edward F; Kansen, Hannah M; Pontoppidan, Bo; Meijer, Yolanda; van der Ent, Cornelis K; Knulst, André C; Sayers, Rebekah; Brown, Helen; Custovic, Adnan; Simpson, Angela; Mills, Claire; Schulz, Juliane; Akkerdaas, Jaap; Totis, Muriel; Capt, Annabelle; Herouet-Guicheney, Corinne; van Ree, Ronald; Banerjee, Tushar; Banerjee, Antima; Claude, Mathilde; Bouchaud, Grégory; Lupi, Roberta; Castan, Laure; Tranquet, Olivier; Denery-Papini, Sandra; Bodinier, Marie; Brossard, Chantal; De Poi, Rosella; Gritti, Elisa; De Dominicis, Emiliano; Popping, Bert; de Laureto, Patrizia P; Palosuo, Kati; Kukkonen, Anna K; Pelkonen, Anna; Mäkelä, Mika; Lee, Nanju A; Rost, Johanna; Muralidharan, Sridevi; Campbell, Dianne; Mehr, Sam; Nock, Catherine; Baumert, Joseph; Taylor, Steve; Mastrorilli, Carla; Tripodi, Salvatore; Caffarelli, Carlo; Perna, Serena; Di Rienzo Businco, Andrea; Sfika, Ifigenia; Dondi, Arianna; Bianchi, Annamaria; Dascola, Carlotta P; Ricci, Giampaolo; Cipriani, Francesca; Maiello, Nunzia; del Giudice, Michele M; Frediani, Tullio; Frediani, Simone; Macrì, Francesco; Pistoletti, Chiara; Iacono, Iride D; Patria, Maria F; Varin, Elena; Peroni, Diego; Comberiati, Pasquale; Chini, Loredana; Moschese, Viviana; Lucarelli, Sandra; Bernardini, Roberto; Pingitore, Giuseppe; Pelosi, Umberto; Olcese, Roberta; Moretti, Matteo; Cirisano, Anastasia; Faggian, Diego; Travaglini, Alessandro; Plebani, Mario; Verga, Maria C; Calvani, Mauro; Giordani, Paolo; Matricardi, Paolo M; Ontiveros, Noe; Cabrera-Chavez, Francisco; Galand, Julie; Beaudouin, Etienne; Pineau, Florence; Sakai, Shinobu; Matsunaga, Kayoko; Teshima, Reiko; Larré, Colette; Denery, Sandra; Tschirner, Sebastian; Trendelenburg, Valérie; Schulz, Gabriele; Niggemann, Bodo; Beyer, Kirsten; Bouferkas, Youcef; Belabbas, Younes; Saidi, Djamel; Kheroua, Omar; Mecherfi, Kamel E E; Guendouz, Malika; Haddi, Abir; Kaddouri, Hanane; Amaral, Luis; Pereira, Ana; Rodrigues, Susana; Datema, Mareen; Jongejan, Laurian; Clausen, Michael; Knulst, Andre; Papadopoulos, Nikolaos; Kowalski, Marek; de Blay, Frédéric; Zwinderman, Aeilko; Hoffman-Sommergruber, Karin; Ballmer-Weber, Barbara; Fernandez-Rivas, Montserrat; Deng, Shan; Yin, Jia; Eisenmann, Charlotte; Nassiri, Maria; Reinert, Rabea; van der Valk, Johanna P M; van Wijk, Roy G; Vergouwe, Yvonne; Steyerberg, Ewout W; Reitsma, Marit; Wichers, Harry J; Savelkoul, Huub F J; Vlieg-Boerstra, Berber; Dubois, Anthony E J; de Jong, Nicolette W; Carolino, Fabrícia; Rodolfo, Ana; Cernadas, Josefina; Roa-Medellín, Dasha; Rodriguez-Fernandez, Ana; Navarro, Joaquín; Albendiz, Vicente; Baeza, María L; Intente-Herrero, Sonsoles; Mikkelsen, Andrea; Mehlig, Kirsten; Lissner, Lauren; Verrill, Linda; Luccioli, Stefano; van Bilsen, Jolanda; Kuper, Frieke; Wolterbeek, André; Rankouhi, Tanja R; Verschuren, Lars; Cnossen, Hilde; Jeurink, Prescilla; Garssen, Johan; Knippels, Léon; Garthoff, Jossie; Houben, Geert; Leeman, Winfried; Eleonore Pettersson, M.; Schins, Afke M M; Koppelman, Gerard H; Kollen, Boudewjin J; Zubchenko, Svitlana; Kuntz, Sarah; Mérida, Pablo; Álvaro, Montserrat; Piquer, Monica; Riggioni, Carmen; Castellanos, Juan H; Jimenez, Rosa; Cap, Melanie; Drumez, Elodie; Lejeune, Stéphanie; Thumerelle, Caroline; Mordacq, Clémence; Nève, Véronique; Ricò, Sonia; Varini, Margherita; Nocerino, Rita; Cosenza, Linda; Amoroso, Antonio; Di Costanzo, Margherita; Di Scala, Carmen; Bedogni, Giorgio; Canani, Roberto B; Turner, Paul J; Poza-Guedes, Paloma; González-Pérez, Ruperto; Sánchez-Machín, Inmaculada; Matheu-Delgado, Victor; Wambre, Erik; Ballegaard, Anne-Sofie; Madsen, Charlotte; Gregersen, Juliane; Bøgh, Katrine L; Aubert, Philippe; Neunlist, Michel; Magnan, Antoine; Lozano-Ojalvo, Daniel; Pablos-Tanarro, Alba; Pérez-Rodríguez, Leticia; Molina, Elena; López-Fandiño, Rosina; Rekima, Akila; Macchiaverni, Patricia; Turfkruyer, Mathilde; Holvoet, Sebastien; Dupuis, Lénaïck; Baiz, Nour; Annesi-Maesano, Isabella; Mercenier, Annick; Nutten, Sophie; Verhasselt, Valérie; Mrakovcic-Sutic, Ines; Banac, Srdan; Sutic, Ivana; Baricev-Novakovic, Zdenka; Sutic, Ingrid; Pavisic, Valentino; Muñoz-Cano, Rosa; Jiménez-Rodríguez, Teodoríkez; Corbacho, Daniel; Roca-Ferrer, Jordi; Bartra, Joan; Bulog, Aleksandar; Micovic, Vladimir; Markiewicz, Lidia; Szymkiewicz, Agata; Szyc, Anna; Wróblewska, Barbara; Harvey, Bryan M; Harthoorn, Lucien F; Wesley Burks, A.; Rentzos, Georgios; Björk, Anna-Lena B; Bengtsson, Ulf; Barber, Colin; Kalicinsky, Chrystyna; Breynaert, Christine; Coorevits, Lieve; Jansen, Cornelia; Van Hoeyveld, Erna; Verbeke, Kristin; Kochuyt, Anne-Marie; Schrijvers, Rik; Deleanu, Diana; Muntean, Adriana; Konstantakopoulou, Maria; Pasioti, Maria; Papadopoulou, Anastasia; Iliopoulou, Anna; Mikos, Nikolaos; Kompoti, Evangelia; de Castro, Eunice D; Bartalomé, Borja; Ue, Kok L; Griffiths, Elizabeth; Till, Stephen; Grimshaw, Kate; Roberts, Graham; Selby, Anna; Butiene, Indre; Larco, Jose I; Dubakiene, Ruta; Fiandor, Ana; Fiocchi, Alessandro; Papadopoulos, Nikos; Sigurdardottir, Sigurveig; Sprikkelman, Aline; Schoemaker, Anne-Fleur; Xepapadaki, Paraskevi; Keil, Thomas; Cojocariu, Zizi; Barbado, Beatriz S; Iancu, Vasti; Arroabarren, Esozia; Esarte, Marta G; Arteaga, Miren; Andrade, Mayra C; Borges, Denise; Kalil, Jorge; Bianchi, Pedro G; Agondi, Rosana C; Gupta, Rinkesh K; Sharma, Akanksha; Gupta, Kriti; Das, Mukul; Dwivedi, Premendra; Karseladze, Rusudan; Jorjoliani, Liana; Saginadze, Lali; Tskhakaia, Mariam; Basello, Katia; Piuri, Gabriele; Speciani, Attilio F; Speciani, Michela C; Camerotto, Carla; Zinno, Francesco; Pakholchuk, Olga; Nedelska, Svitlana; Pattini, Stefano; Costantino, Maria T; Peveri, Silvia; Villalta, Danilo; Savi, Eleonora; Costanzi, Andrea; Revyakina, Vera A; Kiseleva, Marina A; Kuvshinova, Elena D; Larkova, Inna A; Shekhetov, Anton A; Silva, Diana; Moreira, André; Plácido, José; van der Kleij, Hanneke; van Twuijver, Esther; Sutorius, Robbert; de Kam, Pieter-Jan; van Odijk, Jenny; Lindqvist, Helen; Lustig, Elin; Jácome, Amyra A A; Aguilar, Karla L B; Domínguez, Miguel G; Hernández, David A M; Caruso, Cristiano; Casale, Cono; Rapaccini, Gian L; Romano, Antonino; De Vitis, Italo; Cocco, Renata R; Aranda, Carolina; Mallozi, Marcia C; Motta, Jackeline F; Moraes, Lilian; Pastorino, Antonio; Rosario, Nelson; Goudouris, Ekaterini; Porto, Arnaldo; Wandalsen, Neusa F; Sarinho, Emanuel; Sano, Flavio; Solé, Dirceu; Pitsios, Constantinos; Petrodimopoulou, Maria; Papadopoulou, Ekaterini; Passioti, Maria; Kontogianni, Meropi; Adamia, Nino; Khaleva, Ekaterina; del Prado, Ana P; Du Toit, George; Krzych, Edyta; Samolinska-Zawisza, Urszula; Furmanczyk, Konrad; Tomaszewska, Aneta; Raciborski, Filip; Lipiec, Agnieszka; Samel-Kowalik, Piotr; Walkiewicz, Artur; Borowicz, Jacek; Samolinski, Boleslaw; Nano, Aimee L; Recto, Marysia; Somoza, Maria L; López, Natalia B; Alzate, Diana P; Ruano, Francisco J; Garcimartín, Maria I; Haroun, Elisa; de la Torre, Maria V; Rojas, Antonia; Onieva, Montserrat L; Canto, Gabriela; Rodrigues, Alexandra; Forno, Andreia; Cabral, António J; Gonçalves, Rute; Vorozhko, Ilya; Sentsova, Tatyana; Chernyak, Olga; Denisova, Svetlana; Ilènko, Lidia; Muhortnich, Valery; Zimmermann, Caroline; Rohrbach, Alexander; Bakhsh, Faisal R; Boudewijn, Kollen; Oomkes-Pilon, Anne-Marie; Van Ginkle, Dorien; Šilar, Mira; Jeverica, Anja; Vesel, Tina; Avčin, Tadej; Korošec, Peter; van der Valk, Johanna; Berends, Irene; Arends, Nicolette; van Maaren, Maurits; Wichers, Harry; Emons, Joyce; Dubois, Anthony; de Jong, Nicolette; Matsyura, Oksana; Besh, Lesya; Huang, Chung-Hsiung; Jan, Tong-Rong; Stiefel, Gary; Tratt, Jean; Kirk, Kerrie; Carolino, Fabricia; Arasi, Stefania; Caminiti, Lucia; Crisafulli, Giuseppe; Fiamingo, Chiara; Fresta, Jlenia; Pajno, Giovanni; Remington, Ben; Kruizinga, Astrid; Marty Blom, W.; Westerhout, Joost; Bijlsma, Sabina; Baumert, Joe; Blankestijn, Mark; Otten, Henny; Klemans, Rob; Michelsen-Huisman, Anouska D; van Os-Medendorp, Harmieke; Kruizinga, Astrid G; Versluis, Astrid; van Duijn, Gert; de Zeeuw-Brouwer, H. M; Castenmiller, Jacqueline J M; Noteborn, Hub P J M; Houben, Geert F; Bravin, Kristian; Luyt, David; Javed, Bushra; Couch, Phil; Munro, Christopher; Padfield, Phil; Sperrin, Matt; Byrne, Aideen; Oosthuizen, Lizalet; Kelleher, Carina; Ward, Fiona; Brosnan, Niamh; King, Graham; Corbet, Eva; Guzmán, Josué A H; García, Montserrat B; Asensio, Oscar; Navarrete, Laura V; Larramona, Helena; Miró, Xavier D; Pyrz, Katarzyna; Austin, Moira; Boloh, Yanne; Couch, Philip; Galloway, Deirdre; Hernandez, Pilar; Hourihane, Jonathan O; Kenna, Fiona; Majkowska-Wojciechowska, Barbara; Regent, Lynne; Themisb, Marina; Schnadt, Sabine; Semic-Jusufagic, Aida; Galvin, Audrey D; Kauppila, Tiina; Kuitunen, Mikael; Kitsioulis, Nikolaos A; Douladiris, Nikolaos; Kostoudi, Sofia; Manolaraki, Ioanna; Mitsias, Dimitris; Manousakis, Emmanouil; Papadopoulos, Nikolaos G; Knibb, Rebecca; Hammond, Jennifer; Cooke, Richard; Yrjänä, Jaakko; Hanni, Anna-Maija; Vähäsarja, Päivi; Mustonen, Oona; Dunder, Teija; Kulmala, Petri; Lasa, Eva; D’Amelio, Carmen; Martínez, Sara; Joral, Alejandro; Gastaminza, Gabriel; Goikoetxea, Maria J; Candy, David C A; Van Ampting, Marleen T J; Oude Nijhuis, Manon M; Butt, Assad M; Peroni, Diego G; Fox, Adam T; Knol, Jan; Michaelis, Louise J; Padua, Ines; Padrao, Patricia; Moreira, Pedro; Barros, Renata; Sharif, Hanan; Ahmed, Manzoor; Gomaa, Nehad; Mens, Joris; Smit, Koen; Timmermans, Frans; Poredoš, Tomaž; Jeverica, Anja K; Sedmak, Marjeta; Benedik, Evgen; Accetto, Meta; Zupančič, Mirjana; Yonamine, Glauce; Soldateli, Gustavo; Aquilante, Bruna; Pastorino, Antonio C; de Moraes Beck, Cleonir L; Gushken, Andrea K; de Barros Dorna, Mayra; dos Santos, Cristiane N; Castro, Ana P M; Al-Qahtani, Abdulhadi; Arnaout, Rand; Khaliq, Agha R; Amin, Rashid; Sheikh, Farrukh; Alvarez, Jorge; Anda, Marta; Palacios, Miriam; De Prada, Montserrat; Ponce, Carmen; Balbino, Bianca; Sibilano, Riccardo; Marichal, Thomas; Gaudenzio, Nicolas; Karasuyama, Hajime; Bruhns, Pierre; Tsai, Mindy; Reber, Laurent L; Galli, Stephen J; Ferreira, Ana R; Cernadas, Josefina R; del Campo García, Aida; Fernández, Sara P; Carrera, Nerea S; Sánchez-Cruz, Fernando B; Lorenzo, José R F; Claus, Stephanie; Pföhler, Claudia; Ruëff, Franziska; Treudler, Regina; Jaume, Mercedes E; Madroñero, Agustin; Perez, Maria T G; Julia, Juan C; Plovdiv, Charlotte H; Gethings, Lee; Langridge, Jim; Adel-Patient, Karine; Bernard, Hervé; Barcievic-Jones, Ivona; Sokolova, Raditsa; Yankova, Rumyana; Ivanovska, Mariya; Murdjeva, Marianna; Popova, Tatyana; Dermendzhiev, Svetlan; Karjalainen, Martin; Lehnigk, Ulrike; Brown, Duncan; Locklear, Julie C; Locklear, Julie; Maris, Ioana; Hourihane, Jonathan; Ornelas, Cristina; Caiado, Joana; Ferreira, Manuel B; Pereira-Barbosa, Manuel; Puente, Yolanda; Daza, Juan C; Monteseirin, Francisco J; Ukleja-Sokolowska, Natalia; Gawronska-Ukleja, Ewa; Zbikowska-Gotz, Magdalena; Bartuzi, Zbigniew; Sokolowski, Lukasz; Adams, Aine; Mahon, Bernard; English, Karen; Gourdon-Dubois, Nelly; Sellam, Laetitia; Pereira, Bruno; Michaud, Elodie; Messaoudi, Khaled; Evrard, Bertrand; Fauquert, Jean-Luc; Palomares, Francisca; Gomez, Gador; Rodriguez, Maria J; Galindo, Luisa; Molina, Ana; Paparo, Lorella; Mennini, Maurizio; Aitoro, Rosita; Wawrzeńczyk, Adam; Przybyszewski, Michał; Wawrzeńczyk, Anna; Sarıcoban, Hulya E; Ugras, Meltem; Yalvac, Zerrin; Flokstra-de Blok, Bertine M J; van der Velde, J. L; Vereda, Andrea; Ippolito, Clara; Traversa, Amaranta; Adriano, Daniela; Bianchi, Daniela M; Gallina, Silvia; Decastelli, Lucia; Makatsori, Melina; Miles, Anne; Devetak, Sonja P; Devetak, Iztok; Tabet, Soraya A; Trandbohus, Jeanette F; Winther, Pernille; Malling, Hans-Jørgen; Hansen, Kirsten S; Garvey, Lene H; Wang, Chia-Chi; Cheng, Yin-Hua; Tung, Chun-Wei; Dietrich, Mariola; Marenholz, Ingo; Kalb, Birgit; Grosche, Sarah; Blümchen, Katharina; Schlags, Rupert; Price, Mareike; Rietz, Sylke; Esparza-Gordillo, Jorge; Lau, Susanne; Lee, Young-Ae; Almontasheri, Ali; Bahkali, Mohammad A; Elshorbagi, Sahar; Alfhaid, Abdullah; Altamimi, Mashary; Madbouly, Eman; Al-Dhekri, Hassan; Arnaout, Rand K; Basagaña, Maria; Miquel, Sira; Bartolomé, Borja; Brix, Bettina; Rohwer, Stefanie; Brandhoff, Sandra; Berger, Alena; Suer, Waltraud; Weimann, Alf; Bueno, Cristina; Martín-Pedraza, Laura; Abián, Sara; Segundo-Acosta, Pablo S; López-Rodríguez, Juan C; Barderas, Rodrigo; Batanero, Eva; Cuesta-Herranz, Javier; Villalba, María T; Correia, Magna; Benito-Garcia, Filipe; Arêde, Cristina; Piedade, Susana; Morais-Almeida, Mário; Hindley, James; Yarham, Ross; Kuklinska-Pijanka, Anna; Gillick, David; Patient, Karine; Chapman, Martin D; Bøgh, Katrine L; Miranda, Ana; Matos, Eugénia; Sokolova, Anna; Rao, Huan; Baricevic-Jones, Ivona; Smith, Frances; Xue, Wentong; Magnusdottir, Helga; Vidarsdottir, Anna G; Lund, Sigrun; Jensen, Anders B; Ludviksson, Bjorn R; Simon, Reyna; Elfont, Robert; Bennett, Sean; Voyksner, Robert; de Lurdes Torre, Maria; Yürek, Songül; Faber, Margaretha A; Bastiaensen, Annick; Mangodt, Evelyne; van Gasse, Athina; Decuyper, Ine; Sabato, Vito; Hagendorens, Margo M; Bridts, Chris H; De Clerck, Luc S; Ebo, Didier; Schwarz, Susanne; Ziegert, Mandy; Albroscheit, Saskia; Schwager, Christian; Kull, Skadi; Behrends, Jochen; Röckendorf, Niels; Schocker, Frauke; Frey, Andreas; Homann, Arne; Becker, Wolf-Meinhard; Jappe, Uta; Zaabat, Nesrine; Osscini, Sylvia; Agabriel, Chantal; Sterling, Benoît; Carsin, Ania; Liabeuf, Valérie; Maćków, Monica; Zbróg, Alina; Bronkowska, Monica; Courtois, Justine; Gadisseur, Romy; Bertholet, Catherine; Lukas, Pierre; Cavalier, Etienne; Delahaut, Philippe; Quinting, Birgit; Gertmo, Margareta B; Hasseus, Ewa T; Barzylovych, Vladyslava; Oliveira, Júlio; Ensina, Luis F; Aranda, Carolina S; Dopazo, Leire; Lopez, Rebeca; Perez, Raquel; Santos-Diez, Laura; Bilbao, Agurtzane; Garcia, Juan M; Núñez, Ignacio G; Mármol, María Á A; Villarejo, María J B; Martos, José A B; Vergara, Marina S; García, José M I; Michalska, Agata; Sergiejko, Grzegorz; Zacniewski, Robert; Ghiordanescu, Ileana-Maria; Deaconu, Cristina; Popescu, Mihaela; Bumbacea, Roxana S; Ibranji, Alkerta; Nikolla, Elida; Loloci, Gjustina; Juel-Berg, Nanna; Larsen, Lau F; Poulsen, Lars K; Marcelino, João; Prata, Ricardo; Costa, Ana C; Duarte, Fátima; Neto, Marta; Santos, Jennifer; Pestana, Luís C; Sampaio, Daniel; Minale, Paola; Dignetti, Paola; Bignardi, Donatella; Nedelea, Irena; Popescu, Florin-Dan; Vieru, Mariana; Secureanu, Florin-Adrian; Ganea, Carmen S; Vieira, Miguel; Silva, José P M; Watts, Timothy; Watts, Sophia; Lomikovska, Marta; Peredelskaya, Marina; Nenasheva, Natalia; Filipovic, Ivana; Zivkovic, Zorica; Filipovic, Djordje; Higgs, Jennette; Warner, Amena; Jones, Carla (BioMed Central, 2017)
  • Veija, Tuukka; Koljonen, Virve; Bohling, Tom; Kero, Mia; Knuutila, Sakari; Sarhadi, Virinder K (BioMed Central, 2017)
    Abstract Background Distinct characteristic features categorize Merkel cell carcinoma (MCC) into two subgroups according to the Merkel cell polyomavirus infection. Many mutational studies on MCC have been carried out in recent years without identifying a prominent driver mutation. However, there is paucity reporting the expression of cancer genes at the RNA level in MCC tumors. In this study, we studied the RNA expression profiles of 26 MCC tumors, with a goal to identify prospective molecular targets that could improve the treatment strategies of MCC. Methods RNA expression of 50 cancer-related genes in 26 MCC tumors was analyzed by targeted amplicon based next-generation sequencing using the Ion Torrent technology and the expression compared with that of normal, non-cancerous skin samples. Sequencing data were processed using Torrent Suite™ Software. Expression profiles of MCV-negative and MCV-positive tumors were compared. Fluorescence in situ hybridization was performed to study ALK rearrangements and immunohistochemistry to study ALK expression in tumor tissue. Results ALK, CDKN2A, EZH2 and ERBB4 were overexpressed, and EGFR, ERBB2, PDGFRA and FGFR1 were underexpressed in MCC tumors compared to normal skin. In the MCV-negative tumors, MET, NOTCH1, FGFR3, and SMO were overexpressed and JAK3 and NPM1 were under-expressed compared to the MCV-positive tumors. Conclusions High expression of ALK, CDKN2A and EZH2 was recorded in MCC tumors. No ALK fusion was seen by FISH analysis. Overexpression of EZH2 suggests its potential as a drug target in MCC.
  • Aure, Miriam R; Vitelli, Valeria; Jernström, Sandra; Kumar, Surendra; Krohn, Marit; Due, Eldri U; Haukaas, Tonje H; Leivonen, Suvi-Katri; Vollan, Hans K M; Lüders, Torben; Rødland, Einar; Vaske, Charles J; Zhao, Wei; Møller, Elen K; Nord, Silje; Giskeødegård, Guro F; Bathen, Tone F; Caldas, Carlos; Tramm, Trine; Alsner, Jan; Overgaard, Jens; Geisler, Jürgen; Bukholm, Ida R K; Naume, Bjørn; Schlichting, Ellen; Sauer, Torill; Mills, Gordon B; Kåresen, Rolf; Mælandsmo, Gunhild M; Lingjærde, Ole C; Frigessi, Arnoldo; Kristensen, Vessela N; Børresen-Dale, Anne-Lise; Sahlberg, Kristine K (BioMed Central, 2017)
    Abstract Background Breast cancer is a heterogeneous disease at the clinical and molecular level. In this study we integrate classifications extracted from five different molecular levels in order to identify integrated subtypes. Methods Tumor tissue from 425 patients with primary breast cancer from the Oslo2 study was cut and blended, and divided into fractions for DNA, RNA and protein isolation and metabolomics, allowing the acquisition of representative and comparable molecular data. Patients were stratified into groups based on their tumor characteristics from five different molecular levels, using various clustering methods. Finally, all previously identified and newly determined subgroups were combined in a multilevel classification using a “cluster-of-clusters” approach with consensus clustering. Results Based on DNA copy number data, tumors were categorized into three groups according to the complex arm aberration index. mRNA expression profiles divided tumors into five molecular subgroups according to PAM50 subtyping, and clustering based on microRNA expression revealed four subgroups. Reverse-phase protein array data divided tumors into five subgroups. Hierarchical clustering of tumor metabolic profiles revealed three clusters. Combining DNA copy number and mRNA expression classified tumors into seven clusters based on pathway activity levels, and tumors were classified into ten subtypes using integrative clustering. The final consensus clustering that incorporated all aforementioned subtypes revealed six major groups. Five corresponded well with the mRNA subtypes, while a sixth group resulted from a split of the luminal A subtype; these tumors belonged to distinct microRNA clusters. Gain-of-function studies using MCF-7 cells showed that microRNAs differentially expressed between the luminal A clusters were important for cancer cell survival. These microRNAs were used to validate the split in luminal A tumors in four independent breast cancer cohorts. In two cohorts the microRNAs divided tumors into subgroups with significantly different outcomes, and in another a trend was observed. Conclusions The six integrated subtypes identified confirm the heterogeneity of breast cancer and show that finer subdivisions of subtypes are evident. Increasing knowledge of the heterogeneity of the luminal A subtype may add pivotal information to guide therapeutic choices, evidently bringing us closer to improved treatment for this largest subgroup of breast cancer.
  • Helve, Otto; Viljakainen, Heli; Holmlund-Suila, Elisa; Rosendahl, Jenni; Hauta-alus, Helena; Enlund-Cerullo, Maria; Valkama, Saara; Heinonen, Kati; Räikkönen, Katri; Hytinantti, Timo; Mäkitie, Outi; Andersson, Sture (BioMed Central, 2017)
    Abstract Background Vitamin D is important for bone mass accrual during growth. Additionally, it is considered a requirement for a multitude of processes associated with, for example, the development of immunity. Many countries apply vitamin D supplementation strategies in infants, but the guidelines are not based on scientific evidence and aim at prevention of rickets. It remains unclear whether the recommended doses are sufficient for the wide array of other effects of vitamin D. The VIDI trial performed in Finland is the first large randomised controlled study for evaluation of the effects of different vitamin D supplemental doses in infancy on: 1. bone strength 2. infections and immunity 3. allergy, atopy and asthma 4. cognitive development 5. genetic regulation of mineral homeostasis Methods/Design VIDI, a randomised controlled double-blinded single-centre intervention study is conducted in infants from the age of 2 weeks to 24 months. Participants, recruited at Helsinki Maternity Hospital, are randomised to receive daily either 10 μg (400 IU) or 30 μg (1 200 IU) of vitamin D3 supplementation. Both groups are assessed at 6 months of age for calcium homeostasis, and at 12 and 24 months of age for parameters associated with bone strength, growth, developmental milestones, infections, immunity, atopy-related diseases, and genetic factors involved in these functions. Discussion The study enables evaluation of short and long term effects of supplemental vitamin D on growth, immune functions and skeletal and developmental parameters in infants, and the effects of genetic factors therein. The results enable institution of evidence-based guidelines for vitamin D supplementation in infancy. Trial registration ClinicalTrials.gov, NCT01723852 , registration date 6.11.2012.
  • Hankonen, Nelli; Heino, Matti T J; Hynynen, Sini-Tuuli; Laine, Hanna; Araújo-Soares, Vera; Sniehotta, Falko F; Vasankari, Tommi; Sund, Reijo; Haukkala, Ari (BioMed Central, 2017)
    Abstract Background No school-based physical activity (PA) interventions among older adolescents have demonstrated long-term effectiveness, and few of them so far have addressed sedentary behaviour (SB). Based on behavioural theories and evidence, we designed a multi-level intervention to increase PA and decrease SB among vocational school students. This study investigates feasibility and acceptability of two main intervention components and research procedures. We also examine uptake of behaviour change techniques (BCTs) by the participants. Methods Design was an outcome assessor blinded, cluster-randomised controlled trial. Four classes of students (matched pairs) were randomised into one intervention and one control arm. The intervention consisted of (1) a 6-h group-based intervention for students, (2) two 2-h training workshops to reduce their students’ sitting in class for teachers, and (3) provision of light PA equipment in classrooms. At baseline (T1), mid-intervention (T2) at 3 weeks, post-intervention (T3) and 6 months after baseline (T4) we measured hypothesised psychosocial mediators and self-reported PA and sitting. Objective assessment of PA and SB (7-day accelerometry) was conducted at T1, T3 and T4. Body composition (bioimpedance) was measured at T1 and T4. Students and teachers in the intervention arm filled in acceptability questionnaires at T3. Results Recruitment rate was 64% (students) and 88.9% (teachers), and at T3, all post-intervention measurements were completed by 33 students (retention 76.7%) and 15 teachers (retention 93.8%). Acceptability ratings of sessions were high (students M = 6.29, scale 1–7), and data collection procedures were feasible. Intervention arm students reported increased use of BCTs, but uptake of some key BCTs was suboptimal. BCT use correlated highly with objective measures of PA. Based on both self-report and student evaluation, teachers in the intervention arm increased the use of sitting reduction strategies at post-intervention and T4 follow-up (p < .05). Conclusions We detected willingness of the target groups to participate, good response rates to questionnaires, adequate retention, as well as acceptability of the trial protocol. Investigation of BCT use among students helped further enhance intervention procedures to promote BCT use. After making necessary modifications identified, intervention effectiveness can next be tested in a definitive trial. Trial registration ISRCTN34534846 . Registered 23 May 2014. Retrospectively registered.