| 1. |
- Hop, Paul J., et al.
(författare)
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Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS
- 2022
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science. - 1946-6234 .- 1946-6242. ; 14:633
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 samples passing stringent quality control (6763 patients, 2943 controls). We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We then tested 39 DNA methylation-based proxies of putative ALS risk factors and found that high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake were independently associated with ALS. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. Last, DNA methylation at several DMPs and blood cell proportion estimates derived from DNA methylation data were associated with survival rate in patients, suggesting that they might represent indicators of underlying disease processes potentially amenable to therapeutic interventions.
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| 2. |
- Kempen, Thomas G. H., et al.
(författare)
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Potential for pharmacist prescribing in primary care : A Dutch citizen perspective
- 2024
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Ingår i: Exploratory Research in Clinical and Social Pharmacy. - : Elsevier. - 2667-2766. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundMedication prescribing by pharmacists is a task shifting approach to help ensure quality and accessibility of healthcare. In many countries, like the Netherlands, pharmacist prescribing is not legally ensured, and it is unknown what citizens think of its potential introduction.ObjectiveTo investigate citizen perspectives on the potential role of pharmacists in prescribing in primary care.MethodsA Citizen Platform with citizens (>18 years) from the Netherlands was conducted in October 2022. This consisted of a one-day program in which the participants were engaged in interactive assignments and received expert presentations to foster the development of informed opinions. In the final assignment, 3 participant groups designed their ideal future scenario including preconditions regarding the role of the pharmacist in prescribing in primary care. All assignments were recorded, and notes were taken. The researchers then consolidated the 3 scenarios into one version and categorized the preconditions. The Citizen Platform results were summarized and subsequently discussed in 2 online focus groups with other citizens in February 2023 to investigate the perspectives of less informed citizens. Focus group discussions were audio-recorded, transcribed, and thematically analyzed.ResultsThe Citizen Platform (n = 10) resulted in a shared scenario involving a primary care center where general practitioners (GPs) pharmacists and other healthcare professionals collaborate as a team. In this scenario, pharmacists can modify treatment in certain chronic diseases, manage minor ailments and support GPs with the care for patients with complex needs. Preconditions needed to realize this scenario include having shared medical records, the GP retaining the overview of the care for the patient and additional training for pharmacists. The focus groups (n = 6, in total) yielded 5 themes which acknowledge potential pharmacist prescribing but depict a more skeptical view towards pharmacist prescribing and include several concerns, for example pharmacists' potential conflict of interest.ConclusionsCitizens that are informed about opportunities for pharmacy prescribing are capable of sketching potential scenarios for pharmacist prescribing in a collaborative primary care context. Less informed citizens seem more skeptical towards pharmacist prescribing.
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| 3. |
- Majbour, Nour K, et al.
(författare)
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Oligomeric and phosphorylated alpha-synuclein as potential CSF biomarkers for Parkinson's disease.
- 2016
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Ingår i: Molecular Neurodegeneration. - : Springer Science and Business Media LLC. - 1750-1326. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Despite decades of intensive research, to date, there is no accepted diagnosis for Parkinson's disease (PD) based on biochemical analysis of blood or CSF. However, neurodegeneration in the brains of PD patients begins several years before the manifestation of the clinical symptoms, pointing to serious flaw/limitations in this approach.
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| 4. |
- Ek, Åsa, et al.
(författare)
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Training opportunities report
- 2008
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The HILAS (Human Integration in the Life-cycle of Aviation Systems) project is a large, integrated European project which aims to improve safety in the civil air transport sector through the integration of human factors across the life-cycle, while simultaneously generating improved operational efficiencies. The Knowledge Integration strand plays an active role in ensuring that integration takes place across the HILAS project. It initiates activities such as integration workshops, newsletters, HUFAG, dissemination events and lecture series to ensure effective communications both within and external to the consortium. The current report represents a deliverable associated with the dissemination, training and knowledge support activities of the KI strand (WP1.2); more specifically deliverable D1.2.9: Training Opportunities Report. The objective of this deliverable is to identify the training opportunities from HILAS consortium outputs. Several methods are used to identify the training development opportunities arising from HILAS outputs: first, the evaluation of the lecture series 2007; then, the evaluation of WP1.3 deliverables D1.3.1 – 1.3.6; and finally, the interaction with the different HILAS strands (through questionnaires). Together, these complementing evaluations should result in the identification of interesting and relevant training development opportunities arising from HILAS consortium outputs. The evaluation of the lecture series 2007 was described in chapter 3. Results of this evaluation showed that participants were moderately interested in receiving training in the use of the specific tools and/or measures, especially concerning eye tracking and CRIA. Nonetheless, participants appreciated being briefed about the tools and/or measures through the lecture series. The tools and/or measures presented were believed to be useful, relevant and important for the HILAS project, especially with regard to the psychophysiological measures and Pamela. The competence requirements evaluated in WP1.3 deliverables D1.3.1 – 1.3.6 add valuable information to the process of identifying training opportunities. The implementation requirements listed in the deliverables D1.3.1 – D1.3.6 were summarized and, from these, competence/training requirements needed in HILAS organizations were extensively formulated in chapter 4. These competence requirements and the results of the evaluation of the lecture series 2007 together formed the basis for the strand leaders’ questionnaire used for the interaction with the different strands. Interaction with the strands (described in chapter 5) was necessary to identify the specific training opportunities for the different domains. The questions revealed rather diverse results and therefore, it seems difficult to present an all comprising conclusion with respect to the specific training opportunities. Nevertheless, partners have already provided different interesting and relevant training opportunities to implement. Of course, these opportunities often lie within the expertise of the different partners/strands; i.e. opportunities for training that could be developed from the expertise that exists already in the consortium and that is likely to develop as the project progresses. The training platforms that are currently available within the possibilities and constraints of the HILAS project are described in chapter 6. These are lectures series, workshops and the Knowledge Management System. These activities can actually be implemented to acquire knowledge, skills and competencies; in other words to train. It is necessary to extent the use of the available training platforms to the outside world. The development of on-line training via KMS2 and the use of tailored courses are two great examples of this. In addition, lecture series and workshops can be (re-)designed for external stakeholders. The dissemination and integration of knowledge – using these training platforms – is vital to the success of HILAS products beyond the project.
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| 5. |
- Van dijk, Peter R, et al.
(författare)
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After 6years of intraperitoneal insulin administration IGF-I concentrations in T1DM patients are at low-normal level.
- 2015
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Ingår i: Growth Hormone & IGF Research. - : Elsevier BV. - 1096-6374 .- 1532-2238. ; 25:6, s. 316-319
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Low concentrations of insulin-like growth factor-I (IGFI) have been reported in type 1 diabetes mellitus (T1DM), suggested to be due to low insulin concentrations in the portal vein. The aim was to describe the long-term course of IGFI concentrations among T1DM subjects treated with continuous intraperitoneal (IP) insulin infusion (CIPII).DESIGN: Nineteen patients that participated in a randomized cross-over trial comparing CIPII and subcutaneous (SC) insulin therapy in 2006 were followed until 2012. IGF-I measurements were performed at the start of the 2006 study, after the 6month SC- and CIPII treatment phase in 2006 and during CIPII therapy in 2012. Z-scores were calculated to compare the IGF-I concentrations with age-specific normative range values of a non-DM reference population.RESULTS: In 2012, IGF-I Z-scores (-0.7; 95% confidence interval -1.3, -0.2) were significantly higher than at the start of the 2006 study (-2.5; -3.3, -1.8), the end of the SC (-2.0; -2.6, -1.5) and CIPII (-1.6; -2.1, -1.0) treatment phase with a mean difference of: 1.8 (0.9, 2.7), 1.3 (0.5, 2.1) and 0.8 (0.1, 1.6), respectively.CONCLUSION: After 6years of treatment with CIPII, IGF-I concentrations among T1DM patients increased to a level that is higher than during prior SC insulin treatment and is in the lower normal range compared to a non-DM reference population. The results of this study suggest that long-term IP insulin administration influences the IGF system in T1DM.
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| 6. |
- van Dijk, Peter R., et al.
(författare)
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Different Effects of Intraperitoneal and Subcutaneous Insulin Administration on the GH-IGF-1 Axis in Type 1 Diabetes
- 2016
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : ENDOCRINE SOC. - 0021-972X .- 1945-7197. ; 101:6, s. 2493-2501
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Tidskriftsartikel (refereegranskat)abstract
- Context: In type 1 diabetes mellitus, low levels of insulin-like growth factor -1 (IGF-1) and IGF binding protein-3 (IGFBP-3) and high levels of GH and IGFBP-1 are present, probably due to portal vein insulinopenia. Objective: To test the hypothesis that continuous ip insulin infusion (CIPII) has a more pronounced effect than sc insulin therapy on regulation of the GH-IGF-1 axis. Design: This was a prospective, observational case-control study. Measurements were performed twice at a 26-week interval. Setting: Two secondary care hospitals in the Netherlands participated in the study. Patients: There were a total of 184 patients, age-and gender-matched, of which 39 used CIPII and 145 sc insulin therapy for the past 4 years. Outcomes: Primary endpoint included differences in IGF-1. Secondary outcomes were differences in GH, IGFBP-1, and IGFBP-3. Results: IGF-1 was higher with CIPII as compared to SC insulin therapy: 124 mu g/liter (95% confidence interval [CI], 111-138) vs 108 mu g/liter (95% CI 102-115) (P = .035). Additionally, IGFBP-3 concentrations were higher and IGFBP-1 and GH concentrations were lower with CIPII as compared to SC insulin therapy: 3.78 mg/liter (95% CI, 3.49 - 4.10) vs 3.31 mg/liter (95% CI, 3.173.47) for IGFBP-3, 50.9 mu g/liter (95% CI, 37.9 - 68.2) vs 102.6 mu g/liter (95% CI, 87.8 - 119.8) for IGFBP-1 and 0.68 mu g/liter (95% CI, 0.44 - 1.06) vs 1.21 mu g/liter (95% CI, 0.95-1.54) for GH, respectively. In multivariate analysis, IGF-1 had no significant association with HbA1c. Conclusions: The GH-IGF-1 axis may be affected by the route of insulin administration with CIPII counteracting dysregulation of the GH-IGF1 axis present during sc insulin therapy.
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