Browsing by Subject "INTEGRITY"

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  • Rossi, Daniela; Palmio, Johanna; Evila, Anni; Galli, Lucia; Barone, Virginia; Caldwell, Tracy A.; Policke, Rachel A.; Aldkheil, Esraa; Berndsen, Christopher E.; Wright, Nathan T.; Malfatti, Edoardo; Brochier, Guy; Pierantozzi, Enrico; Jordanova, Albena; Guergueltcheva, Velina; Romero, Norma Beatriz; Hackman, Peter; Eymard, Bruno; Udd, Bjarne; Sorrentino, Vincenzo (2017)
    A novel FLNC c.5161delG (p.Gly1722ValfsTer61) mutation was identified in two members of a French family affected by distal myopathy and in one healthy relative. This FLNC c.5161delG mutation is one nucleotide away from a previously reported FLNC mutation (c.5160delC) that was identified in patients and in asymptomatic carriers of three Bulgarian families with distal muscular dystrophy, indicating a low penetrance of the FLNC frameshift mutations. Given these similarities, we believe that the two FLNC mutations alone can be causative of distal myopathy without full penetrance. Moreover, comparative analysis of the clinical manifestations indicates that patients of the French family show an earlier onset and a complete segregation of the disease. As a possible explanation of this, the two French patients also carry a OBSCN c.13330C>T (p.Arg4444Trp) mutation. The p.Arg4444Trp variant is localized within the OBSCN Ig59 domain that, together with Ig58, binds to the ZIg9/ZIg10 domains of titin at Z-disks. Structural and functional studies indicate that this OBSCN p.Arg4444Trp mutation decreases titin binding by similar to 15-fold. On this line, we suggest that the combination of the OBSCN p.Arg4444Trp variant and of the FLNC c.5161delG mutation, can cooperatively affect myofibril stability and increase the penetrance of muscular dystrophy in the French family.
  • 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 (2019)
    BackgroundThe 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(-/7) mice with A. muciniphila for 10weeks and investigated histological, transcriptional and immunological aspects of intestinal health.ResultsThe 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 Ly6C(int) monocyte frequencies in spleen and mesenteric lymph nodes add evidence for the potentially anti-inflammatory properties of A. muciniphila.ConclusionsAltogether, 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.
  • Huck, Olivier; Mulhall, Hannah; Rubin, George; Kizelnik, Zev; Iyer, Radha; Perpich, John D; Haque, Nasreen; Cani, Patrice D; de Vos, Willem M; Amar, Salomon (2020)
    Abstract Aim Akkermansia muciniphila is a beneficial gut commensal, whose anti-inflammatory properties have recently been demonstrated. This study aimed to evaluate the effect of A.muciniphila on Porphyromonas gingivalis elicited inflammation. Material and Methods In lean and obese mice, A.muciniphila was administered in P.gingivalis induced calvarial abcess and in experimental periodontitis model (EIP). Bone destruction and inflammation were evaluated by histomorphometric analysis. In vitro, A.muciniphila was co-cultured with P.gingivalis, growth and virulence factors expression were evaluated. Bone-marrow macrophages (BMM?) and gingival epithelial cells (TIGK) were exposed to both bacterial strains and the expression of inflammatory mediators, as well as tight junction markers was analyzed. Results In a model of calvarial infection, A.muciniphila decreased inflammatory cell infiltration and bone destruction. In EIP, treatment with A.muciniphila resulted in a decreased alveolar bone loss. In vitro, the addition of A.muciniphila to P.gingivalis infected BMM? increased anti-inflammatory IL-10 and decreased IL-12. Additionally, A.muciniphila exposure increases the expression of junctional integrity markers such as integrin-?1, E-cadherin and ZO-1 in TIGK cells. A.muciniphila co-culture with P.gingivalis reduced gingipains mRNA expression. Discussion This study demonstrated the protective effects of A.muciniphila administration and may open consideration to its use as an adjunctive therapeutic agent to periodontal treatment.
  • Uudekll, Peep; Kozlova, Jekaterina; Mandar, Hugo; Link, Joosep; Sihtmae, Mariliis; Kaosaar, Sandra; Blinova, Irina; Kasemets, Kaja; Kahru, Anne; Stern, Raivo; Tatte, Tanel; Kukli, Kaupo; Tamm, Aile (2017)
    Spherical nickel particles with size in the range of 100-400 nm were synthesized by non-aqueous liquid phase benzyl alcohol method. Being developed for magnetically guided biomedical applications, the particles were coated by conformal and antimicrobial thin titanium oxide films by atomic layer deposition. The particles retained their size and crystal structure after the deposition of oxide films. The sensitivity of the coated particles to external magnetic fields was increased compared to that of the uncoated powder. Preliminary toxicological investigations on microbial cells and small aquatic crustaceans revealed non-toxic nature of the synthesized particles.
  • Rajani, Rikesh M.; Ratelade, Julien; Domenga-Denier, Valerie; Hase, Yoshiki; Kalimo, Hannu; Kalaria, Raj N.; Joutel, Anne (2019)
    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic paradigm of small vessel disease (SVD) caused by NOTCH3 mutations that stereotypically lead to the vascular accumulation of NOTCH3 around smooth muscle cells and pericytes. White matter (WM) lesions (WMLs) are the earliest and most frequent abnormalities, and can be associated with lacunar infarcts and enlarged perivascular spaces (ePVS). The prevailing view is that blood brain barrier (BBB) leakage, possibly mediated by pericyte deficiency, plays a pivotal role in the formation of WMLs. Herein, we investigated the involvement of BBB leakage and pericyte loss in CADASIL WMLs. Using post-mortem brain tissue from 12 CADASIL patients and 10 age-matched controls, we found that WMLs are heterogeneous, and that BBB leakage reflects the heterogeneity. Specifically, while fibrinogen extravasation was significantly increased in WMLs surrounding ePVS and lacunes, levels of fibrinogen leakage were comparable in WMLs without other pathology ("pure" WMLs) to those seen in the normal appearing WM of patients and controls. In a mouse model of CADASIL, which develops WMLs but no lacunes or ePVS, we detected no extravasation of endogenous fibrinogen, nor of injected small or large tracers in WMLs. Moreover, there was no evidence of pericyte coverage modification in any type of WML in either CADASIL patients or mice. These data together indicate that WMLs in CADASIL encompass distinct classes of WM changes and argue against the prevailing hypothesis that pericyte coverage loss and BBB leakage are the primary drivers of WMLs. Our results also have important implications for the interpretation of studies on the BBB in living patients, which may misinterpret evidence of BBB leakage within WM hyperintensities as suggesting a BBB related mechanism for all WMLs, when in fact this may only apply to a subset of these lesions.
  • Tammeleht, Anu; Rodriguez-Triana, Maria Jesus; Koort, Kairi; Lofstrom, Erika (2019)
    The increasing concern about ethics and integrity in research communities has brought attention to how students and junior academics can be trained on this regard. Moreover, it is known that ethical behaviour and integrity not only involve individual but also group norms and considerations. Thus, through action research and participant observation, this research investigates the learning processes through which 64 students collaboratively develop research ethics and integrity competencies. The aim was to understand how bachelor, master and PhD students approach ethical dilemma cases through a collaborative process. The data consisted of recorded group work on ethics cases, student group reports, and post-training questionnaires. Later, the analyses considered groups as the unit of analysis. These data were analysed through content analysis utilizing the SOLO taxonomy to identify levels of understanding and assess evolvement of ethical sensitivity during a casebased training session. The results show that all groups reached the level of understanding where the groups demonstrated that concepts had been understood appropriately, but occasionally struggled to make connections between them. Students perceived working collaboratively as beneficial. The results help teachers of research ethics and integrity to make pedagogically justified choices in their teaching. Drawing on the results of this study, we propose a tool for the formative assessment of student learning of research ethics and integrity.
  • Vehviläinen, Sanna; Löfström, Erika; Nevgi, Anne (2018)
    This article deals with the demands that plagiarism places on academic communities, and with the resources staff possess in dealing with these demands. It is suggested that plagiarism ought to be placed in the context of network of intertwining communities (scholarly, pedagogical and administrative), to which participants are engaged to a different extent. The relationship to the ethical issue of plagiarism is related to the subject’s engagement in these communities. The article examines the way teachers deal with plagiarism from the point of view of work engagement and work-related wellbeing. In particular, we analyse job demands created by episodes of dealing with plagiarism as well as job resources teachers possess that aid them in coping with these demands. We used thematic analysis of semi-structured interviews of teachers in two universities. Our results show that the demands fall on five thematic categories: 1. rupture in the personal pedagogical relationship, 2. challenge on the supervisory “gatekeeping” responsibility; 3. a breach of the “everyday normality”; 4. ambivalence in explaining plagiarism and 5. the strain of performing the act of accusation. A key job demand in dealing with plagiarism is that teachers must balance both rule-ethical and care-ethical orientations in their reactions and actions. The resources teachers draw upon when dealing with these demands are: 1) dialogue and reflection in collegial dialogue 2) support from superiors and administration 3) shared protocols, procedures and plagiarism detection software. Our analysis shows that there are various demands that make dealing with plagiarism a strenuous task, but university environments also provide teachers with resources to cope with them.
  • Löfström, Erika; Pyhältö, Kirsi (2017)
    This study explored the perceptions of ethical issues in supervision among doctoral students and supervisors. The nature of ethical issues identified by doctoral students (n = 28) and their supervisors (n = 14) is explored and the degree of fit and misfit between their perceptions in two cases representing the natural and behavioural sciences is analysed. Supervisors and students identified different ethical issues, which suggest that there are aspects in the supervisory relationship about which there is no shared understanding. There were also differences between the ethical issues emphasised in the natural sciences from those emphasised in the behavioural sciences, suggesting differences between the domains.
  • Toomey, E.; Hardeman, W.; Hankonen, N.; Byrne, M.; McSharry, J.; Matvienko-Sikar, K.; Lorencatto, F. (2020)
    Background: Interventions to change behaviour have substantial potential to impact positively on individual and overall public health. Despite an increasing focus on health behaviour change intervention research, interventions do not always have the desired effect on outcomes, while others have diluted effects once implemented into real-life settings. There is little investment into understanding how or why such interventions work or do not work. Methodological inadequacies of trials of behavioural interventions have been previously suggested as a barrier to the quality and advancement of behavioural research, with intervention fidelity acknowledged as a key area for improvement. However, there is much ambiguity regarding the terminology and conceptualisation of intervention fidelity and a lack of practical guidance regarding how to address it sufficiently, particularly within trials of complex behavioural interventions. Objectives: This article outlines specific issues concerning intervention fidelity within trials of health behaviour change interventions and suggests practical considerations and specific recommendations for researchers, with examples from the literature presented. Conclusions: Recommendations pertain to (1) clarifying how fidelity is defined and conceptualised, (2) considering fidelity beyond intervention delivery, (3) considering strategies to both enhance and assess fidelity, (4) making use of existing frameworks and guidance, (5) considering the quality and comprehensiveness of fidelity assessment strategies, (6) considering the balance between fidelity and adaptation and (7) reporting the use of fidelity enhancement and assessment strategies and their results. Suggestions for future research to improve our understanding of, and ability to, address fidelity in behaviour change interventions are also provided.
  • MRI-GENIE & GISCOME Investigators; Int Stroke Genetics Consortium; Bretzner, Martin; Bonkhoff, Anna K.; Schirmer, Markus D.; Strbian, Daniel; Tatlisumak, Turgut; Worrall, Bradford B. (2021)
    Objective: Neuroimaging measurements of brain structural integrity are thought to be surrogates for brain health, but precise assessments require dedicated advanced image acquisitions. By means of quantitatively describing conventional images, radiomic analyses hold potential for evaluating brain health. We sought to: (1) evaluate radiomics to assess brain structural integrity by predicting white matter hyperintensities burdens (WMH) and (2) uncover associations between predictive radiomic features and clinical phenotypes. Methods: We analyzed a multi-site cohort of 4,163 acute ischemic strokes (AIS) patients with T2-FLAIR MR images with total brain and WMH segmentations. Radiomic features were extracted from normal-appearing brain tissue (brain mask-WMH mask). Radiomics-based prediction of personalized WMH burden was done using ElasticNet linear regression. We built a radiomic signature of WMH with stable selected features predictive of WMH burden and then related this signature to clinical variables using canonical correlation analysis (CCA). Results: Radiomic features were predictive of WMH burden (R-2 = 0.855 +/- 0.011). Seven pairs of canonical variates (CV) significantly correlated the radiomics signature of WMH and clinical traits with respective canonical correlations of 0.81, 0.65, 0.42, 0.24, 0.20, 0.15, and 0.15 (FDR-corrected p-values(CV1-6) < 0.001, p-value(CV7) = 0.012). The clinical CV1 was mainly influenced by age, CV2 by sex, CV3 by history of smoking and diabetes, CV4 by hypertension, CV5 by atrial fibrillation (AF) and diabetes, CV6 by coronary artery disease (CAD), and CV7 by CAD and diabetes. Conclusion: Radiomics extracted from T2-FLAIR images of AIS patients capture microstructural damage of the cerebral parenchyma and correlate with clinical phenotypes, suggesting different radiographical textural abnormalities per cardiovascular risk profile. Further research could evaluate radiomics to predict the progression of WMH and for the follow-up of stroke patients' brain health.
  • Ruotsalainen, Ilona; Gorbach, Tetiana; Perkola, Jaana; Renvall, Ville; Syväoja, Heidi J.; Tammelin, Tuija H.; Karvanen, Juha; Parviainen, Tiina (2020)
    Physical activity and exercise beneficially link to brain properties and cognitive functions in older adults, but the findings concerning adolescents remain tentative. During adolescence, the brain undergoes significant changes, which are especially pronounced in white matter. Studies provide contradictory evidence regarding the influence of physical activity or aerobic-exercise on executive functions in youth. Little is also known about the link between both fitness and physical activity with the brain’s white matter during puberty. We investigated the connection between aerobic fitness and physical activity with the white matter in 59 adolescents. We further determined whether white matter interacts with the connection of fitness or physical activity with core executive functions. Our results show that only the level of aerobic fitness, but not of physical activity relates to white matter. Furthermore, the white matter of the corpus callosum and the right superior corona radiata moderates the links of aerobic fitness and physical activity with working memory. Our results suggest that aerobic fitness and physical activity have an unequal contribution to the white matter properties in adolescents. We propose that the differences in white matter properties could underlie the variations in the relationship between either physical activity or aerobic fitness with working memory.
  • Brandstack, Nina; Kurki, T.; Laalo, J.; Kauko, T.; Tenovuo, O. (2016)
    Reproducibility of two different methods for quantifying fiber tracts by using a diffusion tensor imaging (DTI) sequence suitable for clinical magnetic resonance imaging (MRI) protocols was evaluated. DTI of 15 subjects was used to analyze intra-rater and inter-rater reproducibility. Another 10 subjects underwent MRI twice for assessment of between-scan reliability. Ten long association tracts were defined by fiber tracking using inclusion and exclusion regions of interest (ROIs). Whole-tract analysis and tractography-based core analysis were performed, and the effect of fractional anisotropy (FA 0.15/0.30) and turning angle threshold (27A degrees/60A degrees) on reproducibility was evaluated. Additionally, ROI measurements were performed in the core of the tracts. For the tract-based methods, intra-rater and inter-rater reliabilities of FA and mean diffusivity (MD) measurements were excellent. Between-scan reproducibility was good or excellent in 127 of 130 of the measurements. There was no systematic difference in the reproducibility of the FA, MD, and volume measurements depending on the FA or turning angle threshold. For the cross-sectional ROI measurements, reliability showed large variation from poor to excellent depending on the tract. Compared with the commonly used cross-sectional core ROI method, the tract-based analyses seem to be a more robust way to identify and measure white matter tracts of interest, and provide a novel reproducible tool to perform core analysis.
  • Tammeleht, Anu; Rodriguez-Triana, Maria Jesus; Koort, Kairi; Löfström, Erika (2021)
    As development of research ethics competencies is in the focus in higher education (HE) institutions, it is crucial to understand how to support the learning process during such training. While there is plenty of research on how to scaffold children's learning of cognitive skills, there is limited knowledge on how to enhance collaborative case-based learning of research ethics competencies in HE contexts. Our aim was to identify whether, how and when scaffolding is needed with various expertise levels to support development of ethics competencies. To identify and evaluate scaffolding during collaborative case-based ethics training we synthesised a scaffolding framework consisting of three levels: techniques, mechanisms and process. We organised 5 training sessions where 46 participants (including bachelor, master and PhD students as well as junior and senior academics) were involved. Data was collected as part of action research from group-work recordings and transcribed verbatim. Deductive qualitative analysis was implemented on transcripts based on the scaffolding framework. Our analysis revealed that structural scaffolding alone (learning material) is not always efficient with bachelor level students, they also require oral scaffolding when the need becomes apparent. Master's level students benefited most from wording the issues they needed to focus on. Doctoral students and senior academics needed scaffolding to maintain goal orientation. We end our article with some recommendations for facilitators of ethics education, and encourage using the scaffolding framework also in complex problem-solving beyond ethics training.
  • FINGER Study Grp; Stephen, Ruth; Solomon, Alina; Ngandu, Tiia; Levälahti, Esko; Rinne, Juha O.; Kemppainen, Nina; Parkkola, Riitta; Antikainen, Riitta; Strandberg, Timo; Kivipelto, Miia; Soininen, Hilkka; Liu, Yawu (2020)
    Background: Early pathological changes in white matter microstructure can be studied using the diffusion tensor imaging (DTI). It is not only important to study these subtle pathological changes leading to cognitive decline, but also to ascertain how an intervention would impact the white matter microstructure and cognition in persons at-risk of dementia. Objectives: To study the impact of a multidomain lifestyle intervention on white matter and cognitive changes during the 2-year Finnish Geriatric Intervention Study to prevent Cognitive Impairment and Disability (FINGER), a randomized controlled trial in at-risk older individuals (age 60-77 years) from the general population. Methods: This exploratory study consisted of a subsample of 60 FINGER participants. Participants were randomized to either a multidomain intervention (diet, exercise, cognitive training, and vascular risk management, n = 34) or control group (general health advice, n = 26). All underwent baseline and 2-year brain DTI. Changes in fractional anisotropy (FA), diffusivity along domain (F1) and non-domain (F2) diffusion orientations, mean diffusivity (MD), axial diffusivity (AxD), radial diffusivity (RD), and their correlations with cognitive changes during the 2-year multidomain intervention were analyzed. Results: FA decreased, and cognition improved more in the intervention group compared to the control group (p <0.05), with no significant intergroup differences for changes in F1, F2, MD, AxD, or RD. The cognitive changes were significantly positively related to FA change, and negatively related to RD change in the control group, but not in the intervention group. Conclusion: The 2-year multidomain FINGER intervention may modulate white matter microstructural alterations.