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  • Kettunen, Petri; Mäkitalo, Niko (Springer Berlin Heidelberg, 2019)
    Abstract Software is the key enabling technology (KET) as digitalization is cross-cutting future energy systems spanning the production sites, distribution networks, and consumers particularly in electricity smart grids. In this paper, we identify systematically what particular software competencies are required in the future energy systems focusing on electricity system smart grids. The realizations of that can then be roadmapped to specific software capabilities of the different future ‘software houses’ across the networks. Our instrumental method is software competence development scenario path construction with environmental scanning of the related systems elements. The vision of future software-enabled smart energy systems with software houses is mapped with the already progressing scenarios of energy systems transitions on the one hand coupled with the technology foresight of software on the other hand. Grounding on the Smart Grid Reference Architecture Model (SGAM), it tabulates the distinguished software competencies and attributes them to the different parties—including customers/consumers (Internet of People, IoP)—involved in future smart energy systems. The resulting designations can then be used to recognize and measure the necessary software competencies (e.g., fog computing) in order to be able to develop them in-house, or for instance to partner with software companies, depending on the future desirability. Software-intensive systems development competence becomes one of the key success factors for such cyber-physical-social systems (CPSS). Further futures research work is chartered with the Futures Map frame. This paper contributes preliminarily toward that by identifying pictures of the software-enabled futures and the connecting software competence-based scenario paths.
  • Laforet, Celine K; Deksne, Gunita; Petersen, Heidi H; Jokelainen, Pikka; Johansen, Maria V; Lassen, Brian (BioMed Central, 2019)
    Abstract Toxoplasma gondii is a zoonotic parasite of worldwide importance. In this study, we estimated T. gondii seroprevalence in extensively farmed wild boars in Denmark, where little is known about T. gondii in animal hosts. Our study focused on wild boars because they are considered good indicator species for the presence of T. gondii, and wild boar meat is used for human consumption. Serum samples from 101 wild boars collected in 2016–2018 from five different locations from the continental part of Denmark, Jutland, were screened for anti-T. gondii antibodies. The samples were analysed using a commercial indirect enzyme-linked immunosorbent assay (ELISA). Samples from 28 (27.7%) of the 101 wild boars tested positive with the ELISA. The odds for a wild boar to test seropositive were higher if it was sampled during the hunting season 2017–2018 than during 2016–2017 and if it was reported to be at least 1 year old than if it was younger (logistic regression model with the two variables: odds ratios 17.5 and 3.9, respectively). A substantial proportion of the investigated extensively farmed wild boars had been exposed to T. gondii. Moreover, the parasite appeared widespread, at least in the continental part of Denmark, Jutland, as seropositive wild boars were found from all five sampled locations. Assuming seropositivity indicates hosting viable parasites, consumption of undercooked wild boar meat from Denmark is a potential source of T. gondii infections to other hosts, including humans.
  • Sillanpää, Elina; Ollikainen, Miina; Kaprio, Jaakko; Wang, Xiaoling; Leskinen, Tuija; Kujala, Urho M; Törmäkangas, Timo (BioMed Central, 2019)
    Abstract Background Epigenetic clocks may increase our understanding on human aging and how genetic and environmental factors regulate an individual aging process. One of the most promising clocks is Horvath’s DNA methylation (DNAm) age. Age acceleration, i.e., discrepancy between DNAm age and chronological age, tells us whether the person is biologically young or old compared to his/her chronological age. Several environmental and lifestyle factors have been shown to affect life span. We investigated genetic and environmental predictors of DNAm age in young and older monozygotic (MZ) and dizygotic (DZ) twins with a focus on leisure time physical activity. Results Quantitative genetic modeling revealed that the relative contribution of non-shared environmental factors was larger among older compared with younger twin pairs [47% (95% CI 35, 63) vs. 26% (95% CI: 19, 35), p < 0.001]. Correspondingly, genetic variation accounted for less of the variance in older [53% (95% CI 37, 65)] compared with younger pairs [74% (95% CI 65, 82)]. We tested the hypothesis that leisure time physical activity is one of the non-shared environmental factors that affect epigenetic aging. A co-twin control analysis with older same-sex twin pairs (seven MZ and nine DZ pairs, mean age 60.4 years) who had persistent discordance in physical activity for 32 years according to reported/interviewed physical-activity data showed no differences among active and inactive co-twins, DNAm age being 60.7 vs. 61.8 years, respectively [between-group mean-difference: − 1.17 (95%CI − 3.43,1.10)]. Results from the younger cohort of twins supported findings that LTPA is not associated with DNAm age acceleration. Conclusions In older subjects, a larger amount of variance in DNAm age acceleration was explained by non-shared environmental factors compared to young individuals. However, leisure time physical activity during adult years has at most a minor effect on DNAm age acceleration. This is consistent with recent findings that long-term leisure time physical activity in adulthood has little effect on mortality after controlling for genetic factors.
  • De Keyzer, Els L R; De Corte, Zoë; Van Steenberge, Maarten; Raeymaekers, Joost A M; Calboli, Federico C F; Kmentová, Nikol; N’Sibula Mulimbwa, Théophile; Virgilio, Massimiliano; Vangestel, Carl; Mulungula, Pascal M; Volckaert, Filip A M; Vanhove, Maarten P M (BioMed Central, 2019)
    Abstract Background Clupeid fisheries in Lake Tanganyika (East Africa) provide food for millions of people in one of the world’s poorest regions. Due to climate change and overfishing, the clupeid stocks of Lake Tanganyika are declining. We investigate the population structure of the Lake Tanganyika sprat Stolothrissa tanganicae, using for the first time a genomic approach on this species. This is an important step towards knowing if the species should be managed separately or as a single stock. Population structure is important for fisheries management, yet understudied for many African freshwater species. We hypothesize that distinct stocks of S. tanganicae could be present due to the large size of the lake (isolation by distance), limnological variation (adaptive evolution), or past separation of the lake (historical subdivision). On the other hand, high mobility of the species and lack of obvious migration barriers might have resulted in a homogenous population. Results We performed a population genetic study on wild-caught S. tanganicae through a combination of mitochondrial genotyping (96 individuals) and RAD sequencing (83 individuals). Samples were collected at five locations along a north-south axis of Lake Tanganyika. The mtDNA data had low global FST and, visualised in a haplotype network, did not show phylogeographic structure. RAD sequencing yielded a panel of 3504 SNPs, with low genetic differentiation (FST = 0.0054; 95% CI: 0.0046–0.0066). PCoA, fineRADstructure and global FST suggest a near-panmictic population. Two distinct groups are apparent in these analyses (FST = 0.1338 95% CI: 0.1239,0.1445), which do not correspond to sampling locations. Autocorrelation analysis showed a slight increase in genetic difference with increasing distance. No outlier loci were detected in the RADseq data. Conclusion Our results show at most very weak geographical structuring of the stock and do not provide evidence for genetic adaptation to historical or environmental differences over a north-south axis. Based on these results, we advise to manage the stock as one population, integrating one management strategy over the four riparian countries. These results are a first comprehensive study on the population structure of these important fisheries target species, and can guide fisheries management.
  • Kovalchuk, Andriy; Zeng, Zhen; Ghimire, Rajendra P; Kivimäenpää, Minna; Raffaello, Tommaso; Liu, Mengxia; Mukrimin, Mukrimin; Kasanen, Risto; Sun, Hui; Julkunen-Tiitto, Riitta; Holopainen, Jarmo K; Asiegbu, Fred O (BioMed Central, 2019)
    Abstract Background Root and butt rot of conifer trees caused by fungi belonging to the Heterobasidion annosum species complex is one of the most economically important fungal diseases in commercial conifer plantations throughout the Northern hemisphere. We investigated the interactions between Heterobasidion fungi and their host by conducting dual RNA-seq and chemical analysis on Norway spruce trees naturally infected by Heterobasidion spp. We analyzed host and pathogen transcriptome and phenolic and terpenoid contents of the spruce trees. Results Presented results emphasize the role of the phenylpropanoid and flavonoid pathways in the chemical defense of Norway spruce trees. Accumulation of lignans was observed in trees displaying symptoms of wood decay. A number of candidate genes with a predicted role in the higher level regulation of spruce defense responses were identified. Our data indicate a possible role of abscisic acid (ABA) signaling in the spruce defense against Heterobasidion infection. Fungal transcripts corresponding to genes encoding carbohydrate- and lignin-degrading enzymes, secondary metabolism genes and effector-like genes were expressed during the host colonization. Conclusions Our results provide additional insight into defense strategies employed by Norway spruce trees against Heterobasidion infection. The potential applications of the identified candidate genes as markers for higher resistance against root and butt rot deserve further evaluation.
  • Gupta, Richa; van Dongen, Jenny; Fu, Yu; Abdellaoui, Abdel; Tyndale, Rachel F; Velagapudi, Vidya; Boomsma, Dorret I; Korhonen, Tellervo; Kaprio, Jaakko; Loukola, Anu; Ollikainen, Miina (BioMed Central, 2019)
    Abstract Background DNA methylation alteration extensively associates with smoking and is a plausible link between smoking and adverse health. We examined the association between epigenome-wide DNA methylation and serum cotinine levels as a proxy of nicotine exposure and smoking quantity, assessed the role of SNPs in these associations, and evaluated molecular mediation by methylation in a sample of biochemically verified current smokers (N = 310). Results DNA methylation at 50 CpG sites was associated (FDR < 0.05) with cotinine levels, 17 of which are novel associations. As cotinine levels are influenced not only by nicotine intake but also by CYP2A6-mediated nicotine metabolism rate, we performed secondary analyses adjusting for genetic risk score of nicotine metabolism rate and identified five additional novel associations. We further assessed the potential role of genetic variants in the detected association between methylation and cotinine levels observing 124 cis and 3898 trans methylation quantitative trait loci (meQTLs). Nineteen of these SNPs were also associated with cotinine levels (FDR < 0.05). Further, at seven CpG sites, we observed a trend (P < 0.05) that altered DNA methylation mediates the effect of SNPs on nicotine exposure rather than a direct consequence of smoking. Finally, we performed replication of our findings in two independent cohorts of biochemically verified smokers (N = 450 and N = 79). Conclusions Using cotinine, a biomarker of nicotine exposure, we replicated and extended identification of novel epigenetic associations in smoking-related genes. We also demonstrated that DNA methylation in some of the identified loci is driven by the underlying genotype and may mediate the causal effect of genotype on cotinine levels.
  • Arponen, Heidi; Bachour, Adel; Bäck, Leif; Valta, Helena; Mäkitie, Antti; Waltimo-Sirén, Janna; Mäkitie, Outi (BioMed Central, 2018)
    Abstract Background Patients with Osteogenesis imperfecta (OI) suffer from increased bone fracture tendency generally caused by a mutation in genes coding for type I collagen. OI is also characterized by numerous co-morbidities, and recent data from questionnaire studies suggest that these may include increased risk for sleep apnea, a finding that lacks clinical evidence from cohort studies. In this cross-sectional study, 25 adults with OI underwent clinical otorhinolaryngology examination as well as overnight polysomnography to address the question. The participants were aged between 19 and 77 years, and ten of them had mild clinical OI phenotype, seven had a moderately severe phenotype, and eight had a severe phenotype. Results We found obstructive sleep apnea (apnea hypopnea index ≥5/h) in as many as 52% of the OI patients in the cohort. Unexpectedly, however, no correlation was present between sleep apnea and daytime sleepiness, experienced bodily pain, severity of OI, Mallampati score, or neck circumference. Conclusions Seeing that the usual predictors showed no association with occurrence of sleep apnea, we conclude that obstructive sleep apnea may easily be left as an undetected disorder in individuals with OI. Recurrent nocturnal hypoxia due to episodes of apneas can even affect bone metabolism, thereby further aggravating bone fragility in patients with OI.
  • Ilomäki, Liisa; Lakkala, Minna (Springer Singapore, 2018)
    Abstract The aim of this study was to create a model which describes the main elements for improving schools with digital technology and helps to reveal differences between schools and identify their best practices and challenges. The innovative digital school model (IDI school) offers a framework for research but also a research-based model for schools to examine their own practices with digital technologies. The model combines previous research on school improvement, creation of innovations, and digital technology in education as a special case of innovations and learning as knowledge creation to define six main elements describing an innovative, digital school: visions of the school, leadership, practices of the teaching community, pedagogical practices, school-level knowledge practices and digital resources. The model was applied to investigate three basic education schools. The results indicate that the model worked: we found essential differences between the schools and their best practices and challenges for improvement. It worked particularly well for those elements, which are mainly the responsibility for leadership inside a school. The differences of various elements between schools were not based on socioeconomic background but on the school-level practices. As a conclusion, we suggest that to improve schools with digital technology, all elements of the model should be included in the evaluation and development process.
  • Draper, L. A; Ryan, F. J; Smith, M. K; Jalanka, J.; Mattila, E.; Arkkila, P. A; Ross, R. P; Satokari, R.; Hill, C. (BioMed Central, 2018)
    Abstract Background Faecal microbiota transplantation (FMT) is used in the treatment of recurrent Clostridium difficile infection. Its success is typically attributed to the restoration of a diverse microbiota. Viruses (including bacteriophages) are the most numerically dominant and potentially the most diverse members of the microbiota, but their fate following FMT has not been well studied. Results We studied viral transfer following FMT from 3 donors to 14 patients. Recipient viromes resembled those of their donors for up to 12 months. Tracking individual bacteriophage colonisation revealed that engraftment of individual bacteriophages was dependent on specific donor-recipient pairings. Specifically, multiple recipients from a single donor displayed highly individualised virus colonisation patterns. Conclusions The impact of viruses on long-term microbial dynamics is a factor that should be reviewed when considering FMT as a therapeutic option.
  • Vroomans, Renske M A; Hogeweg, Paulien; ten Tusscher, Kirsten H W J (BioMed Central, 2018)
    Abstract Background Segmentation, the subdivision of the major body axis into repeated elements, is considered one of the major evolutionary innovations in bilaterian animals. In all three segmented animal clades, the predominant segmentation mechanism is sequential segmentation, where segments are generated one by one in anterior–posterior order from a posterior undifferentiated zone. In vertebrates and arthropods, sequential segmentation is thought to arise from a clock-and-wavefront-type mechanism, where oscillations in the posterior growth zone are transformed into a segmental prepattern in the anterior by a receding wavefront. Previous evo-devo simulation studies have demonstrated that this segmentation type repeatedly arises, supporting the idea of parallel evolutionary origins in these animal clades. Sequential segmentation has been studied most extensively in vertebrates, where travelling waves have been observed that reflect the slowing down of oscillations prior to their cessation and where these oscillations involve a highly complex regulatory network. It is currently unclear under which conditions this oscillator complexity and slowing should be expected to evolve, how they are related and to what extent similar properties should be expected for sequential segmentation in other animal species. Results To investigate these questions, we extend a previously developed computational model for the evolution of segmentation. We vary the slope of the posterior morphogen gradient and the strength of gene expression noise. We find that compared to a shallow gradient, a steep morphogen gradient allows for faster evolution and evolved oscillator networks are simpler. Furthermore, under steep gradients, damped oscillators often evolve, whereas shallow gradients appear to require persistent oscillators which are regularly accompanied by travelling waves, indicative of a frequency gradient. We show that gene expression noise increases the likelihood of evolving persistent oscillators under steep gradients and of evolving frequency gradients under shallow gradients. Surprisingly, we find that the evolutions of oscillator complexity and travelling waves are not correlated, suggesting that these properties may have evolved separately. Conclusions Based on our findings, we suggest that travelling waves may have evolved in response to shallow morphogen gradients and gene expression noise. These two factors may thus also be responsible for the observed differences between different species within both the arthropod and chordate phyla.
  • Rakkolainen, I.; Lindbohm, J. V; Vuola, J. (BioMed Central, 2018)
    Abstract Background Acute kidney injury (AKI) is a common complication in severe burns and can lead to significantly poorer outcomes. Although the prognosis has improved in recent decades, the mortality of AKI remains considerable. We investigated the factors that increase the risk of AKI and death after severe burn injury. Methods Intensive care patients with ≥20% burned total body surface area (TBSA%) between January 2006 and December 2015 treated in Helsinki Burn Centre were enrolled retrospectively. Patients who arrived > 36 h after burn injury or died < 48 h from arrival were excluded. A total of 187 patients were included in the final analysis. Serum creatinine ≥120 μmol/l (1.4 mg/dl) was the criterion for AKI. Results Fifty-one patients (27.3%) developed AKI during hospital stay and 21 (11.2%) required renal replacement therapy (RRT); 37 patients (19.8%) died during hospital stay. Mortality was significantly higher in the AKI group (52.9%) than in the AKI-negative group (7.4%). The Abbreviated Burn Severity Index (ABSI), Baux, and the modified Baux score were nearly equivalent in predicting mortality during ICU stay (AUC: 0.83–0.84). The risk of death and AKI were minimal with Baux scores < 80. LD50 was 112 for Baux score in all patients. In flame burns, the risk of death increased rapidly after Baux score > 80. Multivariate logistic regression model detected age, TBSA%, sepsis, and rhabdomyolysis as independent risk factors for AKI. Age (per 10 yrs. OR 1.99), TBSA% (per 10% OR 1.64), and AKI predicted mortality during hospital stay; AKI had an odds ratio of (OR) of 5.97 (95% confidence interval [CI] 2.2–16.2). Conclusions Age, TBSA%, and AKI were the strongest independent factors in predicting outcome in severe burns. Even a major burn (> 50% TBSA) has a relatively good prognosis without simultaneous AKI. Prognosis is poorer even in minor burns for patients with AKI.
  • Ruuth, Maija; Soronen, Jarkko; Kaiharju, Essi; Merikanto, Krista; Perttilä, Julia; Metso, Jari; Lee-Rueckert, Miriam; Taskinen, Marja-Riitta; Kovanen, Petri T; Öörni, Katariina; Olkkonen, Vesa M; Jauhiainen, Matti S; Laurila, Pirkka-Pekka (BioMed Central, 2018)
    Abstract Background The focus of studies on high-density lipoproteins (HDL) has shifted from HDL-cholesterol (HDL-C) to HDL function. We recently demonstrated that low USF1 expression in mice and humans associates with high plasma HDL-C and low triglyceride levels, as well as protection against obesity, insulin resistance, and atherosclerosis. Here, we studied the impact of USF1 deficiency on HDL functional capacity and macrophage atherogenic functions, including inflammation, cholesterol efflux, and cholesterol accumulation. Methods We used a congenic Usf1 deficient mice in C57Bl/6JRccHsd background and blood samples were collected to isolate HDL for structural and functional studies. Lentiviral preparations containing the USF1 silencing shRNA expression vector were used to silence USF1 in human THP-1 and Huh-7 cells. Cholesterol efflux from acetyl-LDL loaded THP-1 macrophages was measured using HDL and plasma as acceptors. Gene expression analysis from USF1 silenced peritoneal macrophages was carried out using Affymetrix protocols. Results We show that Usf1 deficiency not only increases HDL-C levels in vivo, consistent with elevated ABCA1 protein expression in hepatic cell lines, but also improves the functional capacity of HDL particles. HDL particles derived from Usf1 deficient mice remove cholesterol more efficiently from macrophages, attributed to their higher contents of phospholipids. Furthermore, silencing of USF1 in macrophages enhanced the cholesterol efflux capacity of these cells. These findings are consistent with reduced inflammatory burden of USF1 deficient macrophages, manifested by reduced secretion of pro-inflammatory cytokines MCP-1 and IL-1β and protection against inflammation-induced macrophage cholesterol accumulation in a cell-autonomous manner. Conclusions Our findings identify USF1 as a novel factor regulating HDL functionality, showing that USF1 inactivation boosts cholesterol efflux, reduces macrophage inflammation and attenuates macrophage cholesterol accumulation, linking improved macrophage cholesterol metabolism and inflammatory pathways to the antiatherogenic function of USF1 deficiency.
  • Hietikko, Minna; Koskinen, Outi; Kurppa, Kalle; Laurila, Kaija; Saavalainen, Päivi; Salmi, Teea; Ilus, Tuire; Huhtala, Heini; Kaukinen, Katri; Lindfors, Katri (BioMed Central, 2018)
    Abstract Background In coeliac disease, ingestion of gluten induces the production of transglutaminase 2 (TG2)-targeted autoantibodies by TG2-specific plasma cells present at high frequency in the small intestinal mucosa in untreated disease. During treatment with a gluten-free diet (GFD), the number of these cells decreases considerably. It has not been previously investigated whether the cells are also present prior to development of villous atrophy, or in non-responsive patients and those with dietary lapses. We aimed to define the frequency of small bowel mucosal TG2-specific plasma cells in coeliac disease patients with varying disease activity, and to investigate whether the frequency correlates with serum and small intestinal TG2-targeting antibodies as well as mucosal morphology and the number of intraepithelial lymphocytes. Results Mucosal TG2-specific plasma cells were found in 79% of patients prior to development of mucosal damage, in all patients with villous atrophy, and in 63% of the patients after 1 year on GFD. In these disease stages, TG2-specific plasma cells accounted for median of 2.3, 4.3, and 0.7% of all mucosal plasma cells, respectively. After long-term treatment, the cells were present in 20% of the patients in clinical remission (median 0%) and in 60% of the patients with poor dietary adherence (median 5.8%). In patients with non-responsive coeliac disease despite strict GFD, the cells were found in only one (9%) subject; the cells accounted for 2.4% of all plasma cells. A positive correlation between the percentage of TG2-specific plasma cells and serum TG2 antibody levels (rS = 0.69, P < 0.001) and the intensity of mucosal TG2-targeting IgA deposits (rS = 0.43, P < 0.001) was observed. Conclusions Our results show that TG2-specific plasma cells are already detectable prior to villous atrophy, and that generally their frequency increases during overt disease. By contrast, on GFD, the percentage of these cells decreases. Overall, the presence of TG2-specific plasma cells in the small bowel mucosa mirrors the presence of gluten in the diet, but the frequency is not always parallel to the level of serum or intestinal TG2 antibodies. These findings increase the knowledge about the development of the TG2 plasma cell responses especially in the early phases of coeliac disease.
  • Li, Li; Huang, Yulun; Gao, Yuge; Shi, Tengfei; Xu, Yunyun; Li, Huini; Hyytiäinen, Marko; Keski-Oja, Jorma; Jiang, Qiuying; Hu, Yizhou; Du, Zhimin (BioMed Central, 2018)
    Abstract Background Glioblastoma multiforme (GBM) is the most malignant central nervous system tumor. Alkylating agent, temozolomide (TMZ), is currently the first-line chemotherapeutic agent for GBM. However, the sensitivity of GBM cells to TMZ is affected by many factors. And, several clinic trials, including co-administration of TMZ with other drugs, have failed in successful treatment of GBM. We have previously reported that Netrin-4 (NTN4), a laminin-like axon guidance protein, plays a protective role in GBM cell senescence upon TMZ-triggered DNA damage. However, the master regulator of NTN4 needs further elucidation. Epidermal growth factor/Epidermal growth factor receptor (EGF/EGFR) can modulate the expression of various extracellular matrix related molecules, and prevent DNA damage in GBM cells. In this study, we investigated the relationship between EGF/EGFR signaling and NTN4, and explored their effect on therapeutic efficacy in GBM cells upon TMZ treatment. Methods Co-expression analysis were performed by using the RNA sequencing data from NIH 934 cell lines and from single cell RNA sequencing data of GBM tumor. The co-expressing genes were used for GO enrichment and signaling pathway enrichment. mRNA expression of the target genes were quantified by qPCR, and cell senescence were investigated by Senescence-Associated Beta-Galactosidase Staining. Protein phosphorylation were observed and analyzed by immunoblotting. The RNA sequencing data and clinical information of TMZ treated patients were extracted from TCGA-glioblastoma project, and then used for Kaplan-Meier survival analysis. Results Analysis of RNA sequencing data revealed a potential co-expression relationship between NTN4 and EGFR. GO enrichment of EGFR-correlated genes indicated that EGFR regulates GBM cells in a manner similar to that in central nervous system development and neural cell differentiation. Pathway analysis suggested that EGFR and its related genes contribute to cell adhesion, extracellular matrix (ECM) organization and caspase related signaling. We also show that EGF stimulates NTN4 expression in GBM cells and cooperates with NTN4 to attenuate GBM cell senescence induced by DNA damage, possibly via AKT and ERK. Clinical analysis showed that co-expression of EGFR and NTN4 significantly predicts poor survival in TMZ-treated GBM patients. Conclusions This study indicates that EGF/EGFR regulates and cooperates with NTN4 in DNA damage resistance in GBM. Therefore, our findings provide a potential therapeutic target for GBM.
  • Heino, Matti T J; Knittle, Keegan; Haukkala, Ari; Vasankari, Tommi; Hankonen, Nelli (BioMed Central, 2018)
    Abstract Background Literature on persuasion suggests compliance increases when requests are accompanied with a reason (i.e. the “because-heuristic”). The reliability of outcomes in physical activity research is dependent on sufficient accelerometer wear-time. This study tested whether SMS reminders—especially those that provided a rationale—are associated with increased accelerometer wear-time. Methods We conducted a within-trial partially randomised controlled trial during baseline data collection in a school-based physical activity intervention trial. Of 375 participants (mean age = 18.1), 280 (75%) opted to receive daily SMS reminders to wear their accelerometers. These 280 participants were then randomised to receive either succinct reminders or reminders including a rationale. Data was analyzed across groups using both frequentist and Bayesian methods. Results No differences in total accelerometer wear minutes were detected between the succinct reminder group (Mdn = 4909, IQR = 3429–5857) and the rationale group (Mdn = 4808, IQR = 3571–5743); W = 8860, p = 0.65, CI95 = − 280.90–447.20. Similarly, we found no differences in wear time between participants receiving SMS reminders (Mdn = 4859, IQR = 3527–5808) and those not receiving them (Mdn = 5067, IQR = 3201–5885); W = 10,642.5, p = 0.77, CI95 = − 424.20–305.30. Bayesian ANOVA favored a model of equal weartime means, over one of unequal means, by a Bayes Factor of 12.05. Accumulated days of valid accelerometer wear data did not differ either. Equivalence testing indicated rejection of effects more extreme than a Cohen’s d (standardised mean difference) of ±~0.3. Conclusions This study casts doubt on the effectiveness of using the because-heuristic via SMS messaging, to promote accelerometer wear time among youth. The because-heuristic might be limited to face-to-face communication and situations where no intention for or commitment to the behavior has yet been made. Other explanations for null effects include non-reading of messages, and reminder messages undermining the self-reminding strategies which would occur naturally in the absence of reminders. Trial registration DRKS DRKS00007721 . Registered 14.04.2015. Retrospectively registered.
  • Eränkö, Elina; Ilander, Mette; Tuomiranta, Mirja; Mäkitie, Antti; Lassila, Tea; Kreutzman, Anna; Klemetti, Paula; Mustjoki, Satu; Hannula-Jouppi, Katariina; Ranki, Annamari (BioMed Central, 2018)
    Abstract Background Netherton syndrome (NS) is a rare life-threatening syndrome caused by SPINK5 mutations leading to a skin barrier defect and a severe atopic diathesis. NS patients are prone to bacterial infections, but the understanding of the underlying immune deficiency is incomplete. Results We analyzed blood lymphocyte phenotypes and function in relation to clinical infections in 11 Finnish NS patients, aged 3 to 17 years, and healthy age-matched controls. The proportion of B cells (CD19+) and naïve B cells (CD27−, IgD+) were high while memory B cells (CD27+) and switched memory B cells (CD27+IgM−IgD−), crucial for the secondary response to pathogens, was below or in the lowest quartile of the reference values in 8/11 (73%) and 9/11 (82%) patients, respectively. The proportion of activated non-differentiated B cells (CD21low, CD38low) was below or in the lowest quartile of the reference values in 10/11 (91%) patients. Despite normal T cell counts, the proportion of naïve CD4+ T cells was reduced significantly and the proportion of CD8+ T central memory significantly elevated. An increased proportion of CD57+ CD8+ T cells indicated increased differentiation potential of the T cells. The proportion of cytotoxic NK cells was elevated in NS patients in phenotypic analysis based on CD56DIM, CD16+ and CD27− NK cells but in functional analysis, decreased expression of CD107a/b indicated impaired cytotoxicity. The T and NK cell phenotype seen in NS patients also significantly differed from that of age-matched atopic dermatitis (AD) patients, indicating a distinctive profile in NS. The frequency of skin infections correlated with the proportion of CD62L+ T cells, naïve CD4+ and CD27+ CD8+ T cells and with activated B cells. Clinically beneficial intravenous immunoglobulin therapy (IVIG) increased naïve T cells and terminal differentiated effector memory CD8+ cells and decreased the proportion of activated B cells and plasmablasts in three patients studied. Conclusions This study shows novel quantitative and functional aberrations in several lymphocyte subpopulations, which correlate with the frequency of infections in patients with Netherton syndrome. IVIG therapy normalized some dysbalancies and was clinically beneficial.
  • Leino, Sakari; Kohtala, Samuel; Rantamäki, Tomi; Koski, Sini K; Rannanpää, Saara; Salminen, Outi (BioMed Central, 2018)
    Abstract Background The treatment of Parkinson’s disease is often complicated by levodopa-induced dyskinesia (LID). Nicotinic acetylcholine receptor agonists can alleviate LID in animal models but may be less effective in conditions of severe dopaminergic denervation. While the mechanisms of LID remain incompletely understood, elevated corticostriatal levels of the brain-derived neurotrophic factor (BDNF) have been suggested to play a role. Here, female mice with near-total unilateral 6-hydroxydopamine-induced nigrostriatal lesions were chronically treated with levodopa, and the effects of the α7 nicotinic receptor partial agonist AZD0328 and nicotine on LID were assessed. At the end of the experiment, BDNF protein levels in the prefrontal cortex and striatum were measured. Results Five-day treatments with three escalating doses of AZD0328 and a 10-week treatment with nicotine failed to alleviate LID. BDNF levels in the lesioned striatum correlated positively with LID severity, but no evidence was found for a levodopa-induced elevation of corticostriatal BDNF in the lesioned hemisphere. The nicotine treatment decreased BDNF levels in the prefrontal cortex but had no effect on striatal BDNF. Conclusions The findings suggest that treatment of LID with nicotinic agonists may lose its effectiveness as the disease progresses, represent further evidence for a role for BDNF in LID, and expand previous knowledge on the effects of long-term nicotine treatment on BDNF.
  • SAARINEN, Sini; SALO, Ari; BOYD, James; LAUKKANEN-NEVALA, Päivi; SILFVAST, Catharina; VIRKKUNEN, Ilkka; SILFVAST, Tom (BioMed Central, 2018)
    Abstract Background Patients resuscitated from out-of-hospital cardiac arrest (OHCA) with pulseless electrical activity (PEA) as initial cardiac rhythm are not always treated in intensive care units (ICUs): some are admitted to high dependency units with various level of care, others to ordinary wards. Aim of this study was to describe the factors determining level of hospital care after OHCA with PEA, post-resuscitation care and survival. Methods Adult OHCA patients with PEA (n = 221), who were resuscitated in southern Finland between 2010 and 2013 were included, provided patient survived to hospital admission. The patients were divided into four groups according to the level of hospital care provided: ordinary ward and Level 1–3 ICUs. Differences in patient characteristics, post-resuscitation care and survival were compared between the groups. Results Most patients (62.4%) were treated at Level 2 ICUs. Longer time to ROSC and advanced age decreased admission rate to Level 2 or 3 post-resuscitation care, whereas good pre-arrest CPC (1–2) increased the admission rate to Level 2/3 ICUs independently. Treatment with targeted temperature management (TTM) (4.1%) or early coronary angiography (3.2%) were very rare. Prognostic decisions were made earlier in the lower treatment intensity groups (p < 0.01). One-year survival rate was 24.0, 17.1% survived with good neurological outcome. Neurological outcome was better with more intensive care. After adjustment, level of care was not independent predictor for outcome: only return of spontaneous circulation (ROSC) time, cardiac arrest cause and pre-arrest performance affected independently to 1-year survival, age and ROSC for neurologic outcome. Conclusions PEA are usually admitted to Level 2 ICUs for post-resuscitation care in the capital area of Finland. Age, ROSC and pre-arrest CPC were independent predictors for level of post-resuscitation care. TTM and early CAG were rare and provided only for Level 3 ICU patients. Prognostication was earlier in lower level of care units. Good neurologic survival was more common with more intensive level of post-resuscitation care. After adjustment, level of care was not independent predictor for survival or neurologic outcome: only ROSC, cardiac arrest cause and pre-arrest performance predicted 1-year survival; age and ROSC neurologic outcome.
  • Repo, Petteri; Matschoss, Kaisa (Springer Berlin Heidelberg, 2018)
    Abstract In recent years, citizen involvement has been increasingly recognised as a source of complementary insights to expert-based foresight. This article analyses citizen visions on desirable and sustainable futures gathered in three recent European involvement projects and reviews how the methodology of topic modelling can be applied to identify commonalities in the visions and how the identified topics are distributed across the citizen involvement projects. A common topic addressing a European citizen desire for wide-ranging societal development with an emphasis on education was identified in the modelling. In addition, three specific topics that correspond to the foci of each involvement project were evident: ‘local production’, ‘cultural variety’ and ‘concerned collectives’. Hence, the results indicate that there are further opportunities for further citizen involvement activities and that specifically focused open-ended envisioning events can contribute to unique sets of citizen-induced topics for the future. These results are particularly useful for the institutionalisation of citizen involvement in foresight studies.
  • Kankaanpää, Meri; Holma-Eriksson, Marika; Kapanen, Sami; Heitto, Merja; Bergström, Sari; Muukkonen, Leila; Harjola, Veli-Pekka (BioMed Central, 2018)
    Abstract Background In this study, we hypothesized that point of care testing (POCT) would reduce length of stay (LOS) in emergency department (ED) when compared to central laboratory testing and be a factor in patient discharge destination. Methods A single centre observational study was performed in ED non-ambulatory patients. Blood testing was performed either with POC instruments for blood gases and chemistry panel, full blood count, and CRP, or at central laboratory, or as a combination of both. Blood draw and POCTs were performed by experienced nurses. Results During the 4-week study period, 1759 patients underwent sample testing (POCT: n = 160, central lab: n = 951; both n = 648). Median waiting time for blood sampling was 19 min less in POCT than central laboratory (0:52 (95% confidence interval (CI) 0:46–1:02) vs. 1:11 (95% CI 1:05–1:14), p < 0.001). POCT results were available faster in both discharge groups, as expected. When imaging was not required, patients in POCT group were discharged home 55 min faster (4:57 (95% CI 3:59–6:17) vs. 5:52 (95% CI 5:21–6:35), p = 0.012) and 1 h 22 min faster when imaging was performed (5:48 (95% CI 5:26–6:18) vs. 7:10 (95% CI 6:47–8:26), p = 0.010). Similar reduction in sampling time and LOS was not seen among those admitted to hospital. Conclusions POCT shortened the laboratory process and made results available faster than the central lab. This allowed patients to be discharged home quicker. Thus, with proper training and education of the ED care team, POCT can be used as an effective tool for improving patient flow.

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