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Uusimmat julkaisut

  • Wiersema, Renske; Koeze, Jacqueline; Hiemstra, Bart; Pettilä, Ville; Perner, Anders; Keus, Frederik; van der Horst, Iwan C C (Springer International Publishing, 2019)
    Abstract Background Acute kidney injury (AKI) occurs in up to 50% of all critically ill patients and hemodynamic abnormalities are assumed to contribute, but their nature and share is still unclear. We explored the associations between hemodynamic variables, including cardiac index and right ventricular function, and the occurrence of AKI in critically ill patients. Methods In this prospective cohort study, we included all patients acutely admitted to an intensive care unit (ICU). Within 24 h after ICU admission clinical and hemodynamic variables were registered including ultrasonographic measurements of cardiac index and right ventricular function, assessed using tricuspid annular plane systolic excursion (TAPSE) and right ventricular systolic excursion (RV S’). Maximum AKI stage was assessed according to the KDIGO criteria during the first 72 h after admission. Multivariable logistic regression modeling was used including both known predictors and univariable significant predictors of AKI. Secondary outcomes were days alive outside ICU and 90-day mortality. Results A total of 622 patients were included, of which 338 patients (54%) had at least AKI stage 1 within 72 h after ICU admission. In the final multivariate model higher age (OR 1.01, 95% CI 1.00–1.03, for each year), higher weight (OR 1.03 CI 1.02–1.04, for each kg), higher APACHE IV score (OR 1.02, CI 1.01–1.03, per point), lower mean arterial pressure (OR 1.02, CI 1.01–1.03, for each mmHg decrease) and lower TAPSE (OR 1.05, CI 1.02–1.09 per millimeter decrease) were all independent predictors for AKI in the final multivariate logistic regression model. Sepsis, cardiac index, RV S’ and use of vasopressors were not significantly associated with AKI in our data. AKI patients had fewer days alive outside of ICU, and their mortality rate was significantly higher than those without AKI. Conclusions In our cohort of acutely admitted ICU patients, the incidence of AKI was 54%. Hemodynamic variables were significantly different between patients with and without AKI. A worse right ventricle function was associated with AKI in the final model, whereas cardiac index was not.
  • Bousquet, J.; Bedbrook, A.; Czarlewski, W.; Onorato, G. L; Arnavielhe, S.; Laune, D.; Mathieu-Dupas, E.; Fonseca, J.; Costa, E.; Lourenço, O.; Morais-Almeida, M.; Todo-Bom, A.; Illario, M.; Menditto, E.; Canonica, G. W; Cecchi, L.; Monti, R.; Napoli, L.; Ventura, M. T; De Feo, G.; Fokkens, W. J; Chavannes, N. H; Reitsma, S.; Cruz, A. A; da Silva, J.; Serpa, F. S; Larenas-Linnemann, D.; Fuentes Perez, J. M; Huerta-Villalobos, Y. R; Rivero-Yeverino, D.; Rodriguez-Zagal, E.; Valiulis, A.; Dubakiene, R.; Emuzyte, R.; Kvedariene, V.; Annesi-Maesano, I.; Blain, H.; Bonniaud, P.; Bosse, I.; Dauvilliers, Y.; Devillier, P.; Fontaine, J. F; Pépin, J. L; Pham-Thi, N.; Portejoie, F.; Picard, R.; Roche, N.; Rolland, C.; Schmidt-Grendelmeier, P.; Kuna, P.; Samolinski, B.; Anto, J. M; Cardona, V.; Mullol, J.; Pinnock, H.; Ryan, D.; Sheikh, A.; Walker, S.; Williams, S.; Becker, S.; Klimek, L.; Pfaar, O.; Bergmann, K. C; Mösges, R.; Zuberbier, T.; Roller-Wirnsberger, R. E; Tomazic, P. V; Haahtela, T.; Salimäki, J.; Toppila-Salmi, S.; Valovirta, E.; Vasankari, T.; Gemicioğlu, B.; Yorgancioglu, A.; Papadopoulos, N. G; Prokopakis, E. P; Tsiligianni, I. G; Bosnic-Anticevich, S.; O’Hehir, R.; Ivancevich, J. C; Neffen, H.; Zernotti, M. E; Kull, I.; Melén, E.; Wickman, M.; Bachert, C.; Hellings, P. W; Brusselle, G.; Palkonen, S.; Bindslev-Jensen, C.; Eller, E.; Waserman, S.; Boulet, L. P; Bouchard, J.; Chu, D. K; Schünemann, H. J; Sova, M.; De Vries, G.; van Eerd, M.; Agache, I.; Ansotegui, I. J; Bewick, M.; Casale, T.; Dykewick, M.; Ebisawa, M.; Murray, R.; Naclerio, R.; Okamoto, Y.; Wallace, D. V (BioMed Central, 2019)
    Abstract Aims Mobile Airways Sentinel NetworK (MASK) belongs to the Fondation Partenariale MACVIA-LR of Montpellier, France and aims to provide an active and healthy life to rhinitis sufferers and to those with asthma multimorbidity across the life cycle, whatever their gender or socio-economic status, in order to reduce health and social inequities incurred by the disease and to improve the digital transformation of health and care. The ultimate goal is to change the management strategy in chronic diseases. Methods MASK implements ICT technologies for individualized and predictive medicine to develop novel care pathways by a multi-disciplinary group centred around the patients. Stakeholders Include patients, health care professionals (pharmacists and physicians), authorities, patient’s associations, private and public sectors. Results MASK is deployed in 23 countries and 17 languages. 26,000 users have registered. EU grants (2018) MASK is participating in EU projects (POLLAR: impact of air POLLution in Asthma and Rhinitis, EIT Health, DigitalHealthEurope, Euriphi and Vigour). Lessons learnt (i) Adherence to treatment is the major problem of allergic disease, (ii) Self-management strategies should be considerably expanded (behavioural), (iii) Change management is essential in allergic diseases, (iv) Education strategies should be reconsidered using a patient-centred approach and (v) Lessons learnt for allergic diseases can be expanded to chronic diseases.
  • Kaila, Marianne; Marjoniemi, Jasmine; Nokireki, Tiina (BioMed Central, 2019)
    Abstract Seventy-two canine serum samples were analyzed for post-vaccination serum titers of rabies antibodies. The samples were divided into two groups: Group 1 dogs (n = 36) were imported dogs from the Russian Federation (n = 31) or Romania (n = 5), with a mean serum antibody titer value of 1.54 IU/mL. Group 2 dogs (n = 36) were Finnish dogs vaccinated in Finland, with a mean titer of 4.19 IU/mL. Altogether, 14 (39%) dogs (CI 95% 23–56) were without detectable antibodies (≤ 0.1 IU/mL) in Group 1, whereas in Group 2, all dogs had an antibody titer greater than 0.1 IU/mL. A statistically significant difference was observed between these groups when comparing the proportions of dogs with antibody levels less than or exceeding 0.5 IU/mL. In Group 1, 19 out of the 36 dogs (CI 95% 36–70) had serum titer values < 0.5 IU/mL, while in Group 2, only 2 dogs had serum titer values < 0.5 IU/mL. Despite the small sample size, this raises concern over the imported dogs having insufficient antibody levels required for international travel and implies that these dogs had perhaps not been vaccinated, even though they had documentation of vaccination upon arrival.
  • de Oliveira Figueiredo, Rejane A; Viljakainen, Jannina; Viljakainen, Heli; Roos, Eva; Rounge, Trine B; Weiderpass, Elisabete (BioMed Central, 2019)
    Abstract Background We aimed to identify different eating habits among Finnish children and to evaluate their association with meal patterns, breakfast consumption, and socio-demographic characteristics in a large, nationwide cohort of children. Methods We evaluated 10,569 children aged 9–14 years into the Finnish Health in Teens cohort in a cross-sectional design. The hierarchical K-means method was used to identify groups of children with different eating habits, based on five factors obtained through factor analysis of 10 food items. Multiple correspondence analysis was used to show associations between groups with different eating habits and meal patterns, breakfast patterns, gender, age, and language spoken at home. Results Analyses identified three groups: unhealthy eaters (12.3%), fruit and vegetable avoiders (43.3%), and healthy eaters (44.1%). Most children had regular meal and breakfast patterns. The proportion of boys was higher among unhealthy eaters. Unhealthy eaters also showed irregular meal and breakfast patterns, and had parents with low education level. There was a higher proportion of girls among healthy eaters. Healthy eaters also showed regular meal and breakfast patterns, and had parents with high education level. Conclusions Although the number of unhealthy eaters was small, special attention should be still paid to these, mostly male children, as they have poor eating habits and they lack regular eating routine. Skipping breakfast was more common among older children and girls, although girls had healthier eating habits overall. Our results can contribute to public health efforts to improve eating behaviours, especially among children with poor eating habits and those skipping healthy food items.
  • Reittu, Hannu; Norros, Ilkka; Räty, Tomi; Bolla, Marianna; Bazsó, Fülöp (Springer Berlin Heidelberg, 2019)
    Abstract We analyze the performance of regular decomposition, a method for compression of large and dense graphs. This method is inspired by Szemerédi’s regularity lemma (SRL), a generic structural result of large and dense graphs. In our method, stochastic block model (SBM) is used as a model in maximum likelihood fitting to find a regular structure similar to the one predicted by SRL. Another ingredient of our method is Rissanen’s minimum description length principle (MDL). We consider scaling of algorithms to extremely large size of graphs by sampling a small subgraph. We continue our previous work on the subject by proving some experimentally found claims. Our theoretical setting does not assume that the graph is generated from a SBM. The task is to find a SBM that is optimal for modeling the given graph in the sense of MDL. This assumption matches with real-life situations when no random generative model is appropriate. Our aim is to show that regular decomposition is a viable and robust method for large graphs emerging, say, in Big Data area.
  • Laatikainen, Reijo; Jalanka, Jonna; Loponen, Jussi; Hongisto, Sanna-Maria; Hillilä, Markku; Koskenpato, Jari; Korpela, Riitta; Salonen, Anne (BioMed Central, 2019)
    Abstract Background A low intake of Fermentable, Oligo-, Di-, Mono-saccharides and Polyols (FODMAPs) is effective in the symptom control of irritable bowel syndrome (IBS) patients but may exert negative effects on the intestinal microbiota. The microbial effects of increasing regular or non-FODMAP fibre sources are largely unknown. Furthermore, it is not known if the baseline microbiota composition is associated with individual symptom control during the consumption of different rye products in IBS patients. Our objective was to evaluate whether increased consumption of low-FODMAP rye bread or regular rye bread for 4 weeks would alter the intestinal microbiota composition of IBS patients following their habitual diet, and whether these changes associate to symptoms and/or the baseline microbiota. Methods The study was conducted as a randomized double blind controlled cross-over study (n = 50). Microbiota was analysed by 16S rRNA gene sequencing and associated with gastrointestinal symptoms. Both microbial changes and their associations to symptoms were secondary outcomes. Results The consumption of the test breads did not alter microbiota diversity. Compared to baseline, consumption of the low FODMAP rye bread decreased the abundance of Bacteroides, Flavonifractor, Holdemania, Parasutterella and Klebsiella and showed a trend towards increased bifidobacteria, whereas the regular rye bread decreased the abundance of Flavonifractor. When comparing between the two test breads, Klebsiella was decreased after low-FODMAP rye bread intake. Patients whose symptoms decreased during the low-FODMAP rye bread displayed more Blautia and less Barnesiella at baseline. Conclusions Consumption of low-FODMAP rye bread had modest, potentially beneficial effects on patients’ microbiota while increasing their intake of fibre substantially. The baseline microbiota composition was associated with the variable degrees of symptom relief experienced by the patients. Consumption of a low-FODMAP rye bread might be one way to increase dietary fibre intake and improve the mild dysbiosis often observed among patients with IBS. Trial registration ClinicalTrials.gov: NCT02161120 . Retrospectively registered 11 June 2014.
  • van der Lugt, Benthe; van Beek, Adriaan A; Aalvink, Steven; Meijer, Ben; Sovran, Bruno; Vermeij, Wilbert P; Brandt, Renata M C; de Vos, Willem M; Savelkoul, Huub F J; Steegenga, Wilma T; Belzer, Clara (BioMed Central, 2019)
    Abstract Background The use of Akkermansia muciniphila as potential therapeutic intervention is receiving increasing attention. Health benefits attributed to this bacterium include an improvement of metabolic disorders and exerting anti-inflammatory effects. The abundance of A. muciniphila is associated with a healthy gut in early mid- and later life. However, the effects of A. muciniphila on a decline in intestinal health during the aging process are not investigated yet. We supplemented accelerated aging Ercc1−/Δ7 mice with A. muciniphila for 10 weeks and investigated histological, transcriptional and immunological aspects of intestinal health. Results The thickness of the colonic mucus layer increased about 3-fold after long-term A. muciniphila supplementation and was even significantly thicker compared to mice supplemented with Lactobacillus plantarum WCFS1. Colonic gene expression profiles pointed towards a decreased expression of genes and pathways related to inflammation and immune function, and suggested a decreased presence of B cells in colon. Total B cell frequencies in spleen and mesenteric lymph nodes were not altered after A. muciniphila supplementation. Mature and immature B cell frequencies in bone marrow were increased, whereas B cell precursors were unaffected. These findings implicate that B cell migration rather than production was affected by A. muciniphila supplementation. Gene expression profiles in ileum pointed toward a decrease in metabolic- and immune-related processes and antimicrobial peptide production after A. muciniphila supplementation. Besides, A. muciniphila decreased the frequency of activated CD80+CD273− B cells in Peyer’s patches. Additionally, the increased numbers of peritoneal resident macrophages and a decrease in Ly6Cint monocyte frequencies in spleen and mesenteric lymph nodes add evidence for the potentially anti-inflammatory properties of A. muciniphila. Conclusions Altogether, we show that supplementation with A. muciniphila prevented the age-related decline in thickness of the colonic mucus layer and attenuated inflammation and immune-related processes at old age. This study implies that A. muciniphila supplementation can contribute to a promotion of healthy aging.
  • Wennstig, Anna-Karin; Garmo, Hans; Isacsson, Ulf; Gagliardi, Giovanna; Rintelä, Niina; Lagerqvist, Bo; Holmberg, Lars; Blomqvist, Carl; Sund, Malin; Nilsson, Greger (BioMed Central, 2019)
    Abstract Background To assess the relationship between radiation doses to the coronary arteries (CAs) and location of a coronary stenosis that required intervention after three-dimensional conformal radiotherapy (3DCRT) for breast cancer (BC). Methods The study population consisted of 182 women treated for BC in Sweden between 1992 and 2012. All women received 3DCRT and subsequently underwent coronary angiography due to a suspected coronary event. CA segments were delineated in the patient’s original planning-CT and radiation doses were recalculated based on the dose distribution of the original radiotherapy (RT) plan. The location of the CA stenosis that required intervention was identified from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). Logistic regression analysis was used to assess the relationship between CA radiation doses and risk of a later coronary intervention at this specific location. Results The odds ratio (OR) varied by radiation dose to the mid left anterior descending artery (LAD) (p = 0.005). Women receiving mean doses of 1–5 Gray (Gy) to the mid LAD had an adjusted OR of 0.90 (95% CI 0.47–1.74) for a later coronary intervention compared to women receiving mean doses of 0–1 Gy to the mid LAD. In women receiving mean doses of 5–20 Gy to the mid LAD, an adjusted OR of 1.24 (95% CI 0.52–2.95) was observed, which increased to an OR of 5.23 (95% CI 2.01–13.6) for mean doses over 20 Gy, when compared to women receiving mean doses of 0–1 Gy to the mid LAD. Conclusions In women receiving conventional 3DCRT for BC between 1992 and 2012, radiation doses to the LAD remained high and were associated with an increased requirement of coronary intervention in mid LAD. The results support that the LAD radiation dose should be considered in RT treatment planning and that the dose should be kept as low as possible. Minimising the dose to LAD is expected to diminish the risk of later radiation-induced stenosis.
  • Katuwal, Sushmita; Tapanainen, Juha S; Pukkala, Eero; Kauppila, Antti (BioMed Central, 2019)
    Abstract Background The length of interval between successive childbirths (birth interval) might influence the incidence of breast cancer, either by stimulating or by inhibiting the factors that are responsible for the initiation of breast cancer or its early development. Methods This is a case-control study nested in a cohort of 47,479 Finnish grand-multiparous (GM) women born after 1934, and registered as having had at least five births before 2013. The 1354 women with breast cancer diagnosis were compared with controls (1:5) matched by parity and date of birth of the mother. Conditional logistic regression was used to estimate odds ratios of the risk of ductal and lobular breast cancer subtypes associated with each of the intervals between the 1st and 5th birth, stratified by age at diagnosis. Age at first and last birth before index date were used as covariates. Results Increased intervals between the 1st and 5th births were associated with an increased risk of lobular breast cancer. In contrast, regarding ductal cancer, premenopausal women with shorter length of interval (< 2 years) between the 1st and 2nd birth had greater risk and longer intervals (3+ years) were associated with reduced risk. Spacing between the 2nd and 5th birth did not influence the risk of ductal breast cancer. Conclusion The findings of our study suggest that the effect of the length of birth interval on breast cancer depends on the age and histology. The protective effect of shorter birth intervals on lobular breast among postmenopausal women and the opposite effect on ductal cancer in premenopausal women may reflect distinct differentiation and functional roles of lobular and ductal cells, and possibly also different response to hormonal exposure.
  • Alekseev, Alexander; Tomppo, Erkki; McRoberts, Ronald E; von Gadow, Klaus (Springer Singapore, 2019)
    Abstract The State Forest Inventory (SFI) in the Russian Federation is a relatively new project that is little known in the English-language scientific literature. Following the stipulations of the Forest Act of 2006, the first SFI sample plots in this vast territory were established in 2007. The 34 Russian forest regions were the basic geographical units for all statistical estimates and served as a first-level stratification, while a second level was based on old inventory data and remotely sensed data. The sampling design was to consist of a simple random sample of 84,700 circular 500 m2 sample plots over forest land. Each sample plot consists of three nested concentric circular subplots with radii of 12.62, 5.64 and 2.82 m and additional subplots for assessing and describing undergrowth, regeneration and ground vegetation. In total, 117 variables were to be measured or assessed on each plot. Although field work has begun, the methodology has elicited some criticism. The simple random sampling design is less efficient than a systematic design featuring sample plot clusters and a mix of temporary and permanent plots. The second-level stratification is mostly ineffective for increasing precision. Qualitative variables, which are not always essential, are dominant, while important quantitative variables are under-represented. Because of very slow progress, in 2018 the original plan was adjusted by reducing the number of permanent sample plots from 84,700 to 68,287 so that the first SFI cycle could be completed by 2020.
  • Seppälä, Toni T; Ahadova, Aysel; Dominguez-Valentin, Mev; Macrae, Finlay; Evans, D. G; Therkildsen, Christina; Sampson, Julian; Scott, Rodney; Burn, John; Möslein, Gabriela; Bernstein, Inge; Holinski-Feder, Elke; Pylvänäinen, Kirsi; Renkonen-Sinisalo, Laura; Lepistö, Anna; Lautrup, Charlotte K; Lindblom, Annika; Plazzer, John-Paul; Winship, Ingrid; Tjandra, Douglas; Katz, Lior H; Aretz, Stefan; Hüneburg, Robert; Holzapfel, Stefanie; Heinimann, Karl; Valle, Adriana D; Neffa, Florencia; Gluck, Nathan; de Vos tot Nederveen Cappel, Wouter H; Vasen, Hans; Morak, Monika; Steinke-Lange, Verena; Engel, Christoph; Rahner, Nils; Schmiegel, Wolff; Vangala, Deepak; Thomas, Huw; Green, Kate; Lalloo, Fiona; Crosbie, Emma J; Hill, James; Capella, Gabriel; Pineda, Marta; Navarro, Matilde; Blanco, Ignacio; ten Broeke, Sanne; Nielsen, Maartje; Ljungmann, Ken; Nakken, Sigve; Lindor, Noralane; Frayling, Ian; Hovig, Eivind; Sunde, Lone; Kloor, Matthias; Mecklin, Jukka-Pekka; Kalager, Mette; Møller, Pål (BioMed Central, 2019)
    Abstract Background Recent epidemiological evidence shows that colorectal cancer (CRC) continues to occur in carriers of pathogenic mismatch repair (path_MMR) variants despite frequent colonoscopy surveillance in expert centres. This observation conflicts with the paradigm that removal of all visible polyps should prevent the vast majority of CRC in path_MMR carriers, provided the screening interval is sufficiently short and colonoscopic practice is optimal. Methods To inform the debate, we examined, in the Prospective Lynch Syndrome Database (PLSD), whether the time since last colonoscopy was associated with the pathological stage at which CRC was diagnosed during prospective surveillance. Path_MMR carriers were recruited for prospective surveillance by colonoscopy. Only variants scored by the InSiGHT Variant Interpretation Committee as class 4 and 5 (clinically actionable) were included. CRCs detected at the first planned colonoscopy, or within one year of this, were excluded as prevalent cancers. Results Stage at diagnosis and interval between last prospective surveillance colonoscopy and diagnosis were available for 209 patients with 218 CRCs, including 162 path_MLH1, 45 path_MSH2, 10 path_MSH6 and 1 path_PMS2 carriers. The numbers of cancers detected within < 1.5, 1.5–2.5, 2.5–3.5 and at > 3.5 years since last colonoscopy were 36, 93, 56 and 33, respectively. Among these, 16.7, 19.4, 9.9 and 15.1% were stage III–IV, respectively (p = 0.34). The cancers detected more than 2.5 years after the last colonoscopy were not more advanced than those diagnosed earlier (p = 0.14). Conclusions The CRC stage and interval since last colonoscopy were not correlated, which is in conflict with the accelerated adenoma-carcinoma paradigm. We have previously reported that more frequent colonoscopy is not associated with lower incidence of CRC in path_MMR carriers as was expected. In contrast, point estimates showed a higher incidence with shorter intervals between examinations, a situation that may parallel to over-diagnosis in breast cancer screening. Our findings raise the possibility that some CRCs in path_MMR carriers may spontaneously disappear: the host immune response may not only remove CRC precursor lesions in path_MMR carriers, but may remove infiltrating cancers as well. If confirmed, our suggested interpretation will have a bearing on surveillance policy for path_MMR carriers.
  • Pekkarinen, Pirkka T; Bäcklund, Minna; Efendijev, Ilmar; Raj, Rahul; Folger, Daniel; Litonius, Erik; Laitio, Ruut; Bendel, Stepani; Hoppu, Sanna; Ala-Kokko, Tero; Reinikainen, Matti; Skrifvars, Markus B (BioMed Central, 2019)
    Abstract Background Organ dysfunction is common after cardiac arrest and associated with worse short-term outcome, but its impact on long-term outcome and treatment costs is unknown. Methods We used nationwide registry data from the intensive care units (ICU) of the five Finnish university hospitals to evaluate the association of 24-h extracerebral Sequential Organ Failure Assessment (24h-EC-SOFA) score with 1-year survival and healthcare-associated costs after cardiac arrest. We included adult cardiac arrest patients treated in the participating ICUs between January 1, 2003, and December 31, 2013. We acquired the confirmed date of death from the Finnish Population Register Centre database and gross 1-year healthcare-associated costs from the hospital billing records and the database of the Finnish Social Insurance Institution. Results A total of 5814 patients were included in the study, and 2401 were alive 1 year after cardiac arrest. Median (interquartile range (IQR)) 24h-EC-SOFA score was 6 (5–8) in 1-year survivors and 7 (5–10) in non-survivors. In multivariate regression analysis, adjusting for age and prior independency in self-care, the 24h-EC-SOFA score had an odds ratio (OR) of 1.16 (95% confidence interval (CI) 1.14–1.18) per point for 1-year mortality. Median (IQR) healthcare-associated costs in the year after cardiac arrest were €47,000 (€28,000–75,000) in 1-year survivors and €12,000 (€6600–25,000) in non-survivors. In a multivariate linear regression model adjusting for age and prior independency in self-care, an increase of one point in the 24h-EC-SOFA score was associated with an increase of €170 (95% CI €150–190) in the cost per day alive in the year after cardiac arrest. In the same model, an increase of one point in the 24h-EC-SOFA score was associated with an increase of €4400 (95% CI €3300–5500) in the total healthcare-associated costs in 1-year survivors. Conclusions Extracerebral organ dysfunction is associated with long-term outcome and gross healthcare-associated costs of ICU-treated cardiac arrest patients. It should be considered when assessing interventions to improve outcomes and optimize the use of resources in these patients.
  • Beck-Nielsen, Signe S; Mughal, Zulf; Haffner, Dieter; Nilsson, Ola; Levtchenko, Elena; Ariceta, Gema; de Lucas Collantes, Carmen; Schnabel, Dirk; Jandhyala, Ravi; Mäkitie, Outi (BioMed Central, 2019)
    Abstract Background X-linked hypophosphatemia (XLH) is an inherited disease of phosphate metabolism in which inactivating mutations of the Phosphate Regulating Endopeptidase Homolog, X-Linked (PHEX) gene lead to local and systemic effects including impaired growth, rickets, osteomalacia, bone abnormalities, bone pain, spontaneous dental abscesses, hearing difficulties, enthesopathy, osteoarthritis, and muscular dysfunction. Patients with XLH present with elevated levels of fibroblast growth factor 23 (FGF23), which is thought to mediate many of the aforementioned manifestations of the disease. Elevated FGF23 has also been observed in many other diseases of hypophosphatemia, and a range of animal models have been developed to study these diseases, yet the role of FGF23 in the pathophysiology of XLH is incompletely understood. Methods The role of FGF23 in the pathophysiology of XLH is here reviewed by describing what is known about phenotypes associated with various PHEX mutations, animal models of XLH, and non-nutritional diseases of hypophosphatemia, and by presenting molecular pathways that have been proposed to contribute to manifestations of XLH. Results The pathophysiology of XLH is complex, involving a range of molecular pathways that variously contribute to different manifestations of the disease. Hypophosphatemia due to elevated FGF23 is the most obvious contributor, however localised fluctuations in tissue non-specific alkaline phosphatase (TNAP), pyrophosphate, calcitriol and direct effects of FGF23 have been observed to be associated with certain manifestations. Conclusions By describing what is known about these pathways, this review highlights key areas for future research that would contribute to the understanding and clinical treatment of non-nutritional diseases of hypophosphatemia, particularly XLH.
  • Patel, Tirth K; Habimana-Griffin, LeMoyne; Gao, Xuefeng; Xu, Baogang; Achilefu, Samuel; Alitalo, Kari; McKee, Celia A; Sheehan, Patrick W; Musiek, Erik S; Xiong, Chengjie; Coble, Dean; Holtzman, David M (BioMed Central, 2019)
    Abstract Background Alzheimer’s disease is characterized by two main neuropathological hallmarks: extracellular plaques of amyloid-β (Aβ) protein and intracellular aggregates of tau protein. Although tau is normally a soluble monomer that bind microtubules, in disease it forms insoluble, hyperphosphorylated aggregates in the cell body. Aside from its role in AD, tau is also involved in several other neurodegenerative disorders collectively called tauopathies, such as progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), some forms of frontotemporal dementia, and argyrophilic grain disease (AGD). The prion hypothesis suggests that after an initial trigger event, misfolded forms of tau are released into the extracellular space, where they spread through different brain regions, enter cells, and seeding previously normal forms. Thus understanding mechanisms regulating the clearance of extracellular tau from the CNS is important. The discovery of a true lymphatic system in the dura and its potential role in mediating Aβ pathology prompted us to investigate its role in regulating extracellular tau clearance. Methods To study clearance of extracellular tau from the brain, we conjugated monomeric human tau with a near-infrared dye cypate, and injected this labeled tau in the parenchyma of both wild-type and K14-VEGFR3-Ig transgenic mice, which lack a functional CNS lymphatic system. Following injection we performed longitudinal imaging using fluorescence molecular tomography (FMT) and quantified fluorescence to calculate clearance of tau from the brain. To complement this, we also measured tau clearance to the periphery by measuring plasma tau in both groups of mice. Results Our results show that a significantly higher amount of tau is retained in the brains of K14-VEGFR3-Ig vs. wild type mice at 48 and 72 h post-injection and its subsequent clearance to the periphery is delayed. We found that clearance of reference tracer human serum albumin (HSA) was also significantly delayed in the K14-VEGFR3-Ig mice. Conclusions The dural lymphatic system appears to play an important role in clearance of extracellular tau, since tau clearance is impaired in the absence of functional lymphatics. Based on our baseline characterization of extracellular tau clearance, future studies are warranted to look at the interaction between tau pathology and efficiency of lymphatic function.
  • De Fazio, Chiara; Skrifvars, Markus B; Søreide, Eldar; Creteur, Jacques; Grejs, Anders M; Kjærgaard, Jesper; Laitio, Timo; Nee, Jens; Kirkegaard, Hans; Taccone, Fabio S (BioMed Central, 2019)
    Abstract Background The aim of this study was to explore the performance and outcomes for intravascular (IC) versus surface cooling devices (SFC) for targeted temperature management (TTM) after out-of-hospital cardiac arrest. Methods A retrospective analysis of data from the Time-differentiated Therapeutic Hypothermia (TTH48) trial (NCT01689077), which compared whether TTM at 33 °C for 48 h results in better neurologic outcomes compared with standard 24-h duration. Devices were assessed for the speed of cooling and rewarming rates. Precision was assessed by measuring temperature variability (TV), i.e., the standard deviation (SD) of all temperature measurements in the cooling phase. Main outcomes were overall mortality and poor neurological outcome, including death, severe disability, or vegetative status. Results A total of 352 patients had available data and were included in the analysis; of those, 218 (62%) were managed with IC. A total of 114/218 (53%) patients with IC and 61/134 (43%) with SFC were cooled for 48 h (p = 0.22). Time to target temperature (≤ 34 °C) was significantly shorter for patients treated with endovascular devices (2.2 [1.1–4.0] vs. 4.2 [2.7–6.0] h, p < 0.001), but temperature was also lower on admission (35.0 [34.2–35.6] vs. 35.3 [34.5–35.8]°C; p = 0.02) and cooling rate was similar (0.4 [0.2–0.8] vs. 0.4 [0.2–0.6]°C/h; p = 0.14) when compared to SFC. Temperature variability was significantly lower in the endovascular device group when compared with SFC methods (0.6 [0.4–0.9] vs. 0.7 [0.5–1.0]°C; p = 0.007), as was rewarming rate (0.31 [0.22–0.44] vs. 0.37 [0.29–0.49]°C/hour; p = 0.02). There was no statistically significant difference in mortality (endovascular 65/218, 29% vs. others 43/134, 32%; p = 0.72) or poor neurological outcome (endovascular 69/218, 32% vs. others 51/134, 38%; p = 0.24) between type of devices. Conclusions Endovascular cooling devices were more precise than SFC methods in patients cooled at 33 °C after out-of-hospital cardiac arrest. Main outcomes were similar with regard to the cooling methods.
  • Yan, Wen; Chen, Qian; Zhang, Xuemei; Elovainio, Marko; Huang, Yan (BioMed Central, 2019)
    Abstract Background The use of guidelines has shown to improve clinical practice process and structure of health care, but health care providers don’t always use and keep up-to-date with the new clinical practice guidelines. Nurses’ attitudes towards guidelines have shown to be the most frequently identified factor affecting their actual use of clinical practice guidelines, but no instruments for measuring it are available in China. There are scales validated in the western countries, but there is no information about their validity in Chinese health care. The purpose of this study is to test the validity and reliability of Chinese Attitudes towards guidelines - scale for nurses. Methods The study was conducted from April to July 2017. The Attitudes towards guidelines scale was translated into Chinese with forward-backward translation method and a questionnaire survey was conducted. Eight hundred randomly selected nurses (final N = 768) from Geriatrics, Internal medical and Rehabilitation departments of 16 hospitals were drawn in Sichuan province, China. Construct validity was evaluated by exploratory and confirmatory factor analysis, and reliability was assessed by test-retest reliability (represented by intra class correlation) and internal consistency (expressed by Cronbach’s coefficients). The test-retest reliability was examined with a sample of 32 clinical nurses who filled out the questionnaire 14 days after the first survey. Results Exploratory factor analysis supported a four-factor model for the Chinese version of the scale. Confirmatory factor analysis indicated that the hypothetical four-factor model fitted the data relatively well. The intra class correlation coefficient was 0.85 (95%CI, 0.68–0.93) and the Cronbach’s alpha values for the four subscales ranged from 0.645 to 0.912. Conclusions The results support the acceptable level of validity and reliability of the Chinese version of Attitudes towards guidelines scale, which can be used to assess nurses’ attitudes towards guidelines in China. Future testing for the Chinese version of Attitudes towards guidelines scale needs to be carried out to see whether these results are generalizable to other professionals and occupational groups and to be used to revise attitudes towards specific guidelines in China.
  • Trevisan, Chiara; Sotiraki, Smaragda; Laranjo-González, Minerva; Dermauw, Veronique; Wang, Ziqi; Kärssin, Age; Cvetkovikj, Aleksandar; Winkler, Andrea S; Abraham, Annette; Bobić, Branko; Lassen, Brian; Cretu, Carmen M; Vasile, Cozma; Arvanitis, Dimitris; Deksne, Gunita; Boro, Ilievski; Kucsera, István; Karamon, Jacek; Stefanovska, Jovana; Koudela, Břetislav; Pavlova, Maja J; Varady, Marian; Pavlak, Marina; Šarkūnas, Mindaugas; Kaminski, Miriam; Djurković-Djaković, Olgica; Jokelainen, Pikka; Jan, Dagny S; Schmidt, Veronika; Dakić, Zorica; Gabrië, Sarah; Dorny, Pierre; Omeragić, Jasmin; Alagić, Davor; Devleesschauwer, Brecht (BioMed Central, 2019)
    In the original article [1], the authors Dr Jasmin OMERAGIĆ and Dr Davor ALAGIĆ were erroneously omitted from the co-authors list.
  • Zakrzewski-Fruer, Julia K; Gillison, Fiona B; Katzmarzyk, Peter T; Mire, Emily F; Broyles, Stephanie T; Champagne, Catherine M; Chaput, Jean-Philippe; Denstel, Kara D; Fogelholm, Mikael; Hu, Gang; Lambert, Estelle V; Maher, Carol; Maia, José; Olds, Tim; Onywera, Vincent; Sarmiento, Olga L; Tremblay, Mark S; Tudor-Locke, Catrine; Standage, Martyn (BioMed Central, 2019)
    Abstract Background Existing research has documented inconsistent findings for the associations among breakfast frequency, physical activity (PA), and sedentary time in children. The primary aim of this study was to examine the associations among breakfast frequency and objectively-measured PA and sedentary time in a sample of children from 12 countries representing a wide range of human development, economic development and inequality. The secondary aim was to examine interactions of these associations between study sites. Methods This multinational, cross-sectional study included 6228 children aged 9–11 years from the 12 International Study of Childhood Obesity, Lifestyle and the Environment sites. Multilevel statistical models were used to examine associations between self-reported habitual breakfast frequency defined using three categories (breakfast consumed 0 to 2 days/week [rare], 3 to 5 days/week [occasional] or 6 to 7 days/week [frequent]) or two categories (breakfast consumed less than daily or daily) and accelerometry-derived PA and sedentary time during the morning (wake time to 1200 h) and afternoon (1200 h to bed time) with study site included as an interaction term. Model covariates included age, sex, highest parental education, body mass index z-score, and accelerometer waking wear time. Results Participants averaged 60 (s.d. 25) min/day in moderate-to-vigorous PA (MVPA), 315 (s.d. 53) min/day in light PA and 513 (s.d. 69) min/day sedentary. Controlling for covariates, breakfast frequency was not significantly associated with total daily or afternoon PA and sedentary time. For the morning, frequent breakfast consumption was associated with a higher proportion of time in MVPA (0.3%), higher proportion of time in light PA (1.0%) and lower min/day and proportion of time sedentary (3.4 min/day and 1.3%) than rare breakfast consumption (all p ≤ 0.05). No significant associations were found when comparing occasional with rare or frequent breakfast consumption, or daily with less than daily breakfast consumption. Very few significant interactions with study site were found. Conclusions In this multinational sample of children, frequent breakfast consumption was associated with higher MVPA and light PA time and lower sedentary time in the morning when compared with rare breakfast consumption, although the small magnitude of the associations may lack clinical relevance. Trial registration The International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE) is registered at (Identifier NCT01722500 ).
  • Zhu, Zhen; Sippola, Perttu; Ylivaara, Oili M E; Modanese, Chiara; Di Sabatino, Marisa; Mizohata, Kenichiro; Merdes, Saoussen; Lipsanen, Harri; Savin, Hele (Springer US, 2019)
    Abstract In this work, we report the successful growth of high-quality SiO2 films by low-temperature plasma-enhanced atomic layer deposition using an oxidant which is compatible with moisture/oxygen sensitive materials. The SiO2 films were grown at 90 °C using CO2 and Bis(tertiary-butylamino)silane as process precursors. Growth, chemical composition, density, optical properties, and residual stress of SiO2 films were investigated. SiO2 films having a saturated growth-per-cycle of ~ 1.15 Å/cycle showed a density of ~ 2.1 g/cm3, a refractive index of ~ 1.46 at a wavelength of 632 nm, and a low tensile residual stress of ~ 30 MPa. Furthermore, the films showed low impurity levels with bulk concentrations of ~ 2.4 and ~ 0.17 at. % for hydrogen and nitrogen, respectively, whereas the carbon content was found to be below the measurement limit of time-of-flight elastic recoil detection analysis. These results demonstrate that CO2 is a promising oxidizing precursor for moisture/oxygen sensitive materials related plasma-enhanced atomic layer deposition processes.
  • Lommi, Henri; Koponen, Ismo T. (Springer International Publishing, 2019)
    Abstract We examine students’ representations of their conceptions of the interlinked nature of science history and general history, as well as cultural history. Such knowledge landscapes of the history of science are explored by using the knowledge cartographic, network-based method of analysis to reveal the key items, landmarks, of the landscapes. We show that Katz centrality and Katz centrality efficiency are robust and reliable measures for finding landmarks. It is shown that landmarks are most often persons but include also colligatory landmarks, which refer to broader sets of events or ideas. By using Katz centrality we study how landmarks depend on periodisation of the networks to see what kinds of changes occur by changing the time window on history. The community structure of the networks is studied by using the Louvain method, to reveal the strong thematic dependence of the communities. When landmarks are studied in relation to community structure, it is found that colligatory landmarks gain importance in relation to person-centred landmarks. Network-based cartography thus reveals many features about landmarks, how communities emerge around them and how they depend on periodisation, which traditional methods can only detect or identify with difficulty. Such knowledge has direct impact on the design and planning of education and courses which could better address the need to facilitate a deeper understanding of the related nature of science history and history in general.

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