276557 research outputs found
Sort by
Optimization and personalization of antisense therapy for myotonic dystrophy type 1
No full textContains fulltext :
326049.pdf (Publisher’s version ) (Open Access)Myotonic dystrophy type 1 (DM1) is a rare genetic disorder that affects muscles and multiple other body systems. Symptoms can therefore vary widely, ranging from muscle weakness to heart and breathing problems. DM1 is caused by long repetitions in the DMPK gene, which produce toxic RNA that traps a protein called MBNL1. The higher the number of repetitions, the more severe the illness becomes, and it often worsens across generations. Although there is no cure yet, antisense oligonucleotide (ASO) drugs that target the toxic RNA show most promise. This thesis tested two ASO strategies using nanoparticles, to improve drug delivery, and investigated how longer or shorter repetitions affect drug response. Results indicate that while both strategies help, one does so with fewer side effects. Also, tailoring these therapies to a patient’s genetic profile, already in the laboratory, may be key to paving the way towards personalized therapies for DM1.Radboud University, 08 december 2025Promotores : Brock, R.E., Wansink, D.G.162 p
Radical Isomerization upon Dissociative Electron Ionization of Anthracene and Phenanthrene
No full textContains fulltext :
324155.pdf (Publisher’s version ) (Closed access)12 september 20259 p
20 years of the Family Reunification Directive. Central Themes, Problem Issues and Implementation in Selected Member States
No full textItem does not contain fulltex
Assessing Safety of the Transition to Generic Imatinib in Patients with Gastrointestinal Stromal Tumours
No full textContains fulltext :
322939.pdf (Publisher’s version ) (Open Access)01 juli 202512 p
The effectiveness of adding Braun anastomosis to standard Child reconstruction to reduce delayed gastric emptying after pancreatoduodenectomy (REMBRANDT): study protocol for a multicentre randomised-controlled trial.
No full textContains fulltext :
324465.pdf (Publisher’s version ) (Open Access)BACKGROUND: Pancreatoduodenectomy (PD) is associated with a high risk of complications, such as delayed gastric emptying (DGE) (19-45%). Patients with DGE experience symptoms of nausea, vomiting, inability to tolerate solid food and prolonged dependence on a nasogastric tube (> 7 days), leading to extended hospital stay. A potential mean to reduce DGE is reconstruction after PD with addition of Braun's enteroenterostomy (BE), an anastomosis between the afferent and efferent jejunal limbs distal to the gastrojejunostomy (GJ). Previous prospective-cohort studies and few small randomised controlled studies demonstrated a beneficial effect of BE in reducing DGE. Aim of this study is to obtain robust evidence for the effectiveness of BE in reducing DGE in patients undergoing PD. METHODS: The REMBRANDT trial is a multicentre, patient-observer blinded, randomised controlled trial. Adult patients undergoing open PD are recruited in 12 participating centres. Primary outcome is the incidence of DGE. Secondary outcomes include postoperative complications, such as postoperative pancreatic fistula, anastomotic leakage and mortality. Additionally, the study will assess length of hospital stay, patient-reported outcomes, functional outcomes after 12 months and costs. Randomisation is performed intraoperatively (1:1) with stratification of groups by centre, with a sample size of 128 patients per arm. DISCUSSION: This trial is designed to evaluate the effectiveness of Braun anastomosis in reducing delayed gastric emptying after open pancreatoduodenectomy. Throughout the trial, semi-structured interviews will be conducted with surgeons in order to perform a barrier-facilitator analysis, allowing for successful implementation of BE if proven effective. TRIAL REGISTRATION: ClinicalTrials.gov NCT05709197. Registered on January 24, 2023
Effects of simulated Martian environmental stressors on specific human pathogen–immune system interactions
No full textContains fulltext :
326471.pdf (Publisher’s version ) (Open Access
Tph2 deficiency leads to alterations in social adjustment and socio-affective communication in neonatal rats: No rescue effect of communal nesting.
No full textContains fulltext :
323931.pdf (Publisher’s version ) (Open Access)Deficiency of tryptophan hydroxylase 2 (TPH2), the rate-limiting enzyme for serotonin (5-hydroxytryptamine, 5-HT) synthesis in the brain, was repeatedly reported to cause impairments in socio-affective communication and maternal affiliation across species, including mice, rats, and monkeys. We recently applied a rescue protocol in the Tph2 knockout rat model and demonstrated that communal nesting ameliorates maternal affiliation impairments. Interestingly, however, this rescue strategy did not lead to improvements in socio-affective communication and was associated with an aggravated growth retardation phenotype in Tph2-deficient offspring. In the present study, we aimed to gain deeper insight into the interplay between socio-affective communication, nesting condition, and test context. To this aim, we studied Tph2(-/-) knockout, Tph2(+/-) heterozygous, and Tph2(+/+) wildtype rat pups of both sexes, randomly assigned to standard versus communal nesting. We performed detailed spectrographic analyses and compared the emission of isolation-induced ultrasonic vocalizations under social test conditions, i.e., the maternal preference test and the homing test, to non-social test conditions, i.e., the isolation box test. Our results show that Tph2 deficiency causes prominent alterations in isolation-induced ultrasonic calling linked to reduced maternal responsiveness, including changes in acoustic features, e.g., increased call duration but reduced frequency modulation. Remarkably, irrespective of communal nesting, Tph2(-/-) pups typically displayed either no evidence for social adjustment or even changes opposite to Tph2(+/+) littermates, suggesting a reduction and/or delay in the capability and/or motivation to appropriately adjust to changes in the social environment. Such alterations in social adjustment likely contribute to growth retardation through reduced quality of mother-pup interactions
Reasons for (Not) Seeking Care for Fatigue and Care Needs Among Patients With Inflammatory Bowel Disease: A Qualitative Interview Study.
No full textContains fulltext :
324105.pdf (Publisher’s version ) (Open Access)AIMS: To explore reasons why patients with inflammatory bowel disease (IBD) do (not) engage in fatigue-related care and their care needs. DESIGN: A qualitative interview study, using a phenomenological methodological approach. METHODS: We included 16 fatigued patients with IBD in remission. Data were collected between December 2021 and March 2022, using semi-structured interviews. Template analysis was performed. RESULTS: We identified six themes regarding reasons why (not) to seek care for fatigue: (1) Cognitions about fatigue and coping with fatigue, (2) perceptions of fatigue-related care and previous care experiences, (3) perceived knowledge and behaviour of healthcare professionals, (4) physical and emotional well-being, (5) social relationships and support, and (6) practical factors. Regarding their care needs, patients reported a need for a holistic and person-centred care approach, with healthcare professionals actively addressing fatigue and offering care. They suggested a range of options for what care to offer, including eliminating physical causes of fatigue, discussing medication options, providing information on fatigue management, lifestyle support, psychological support, peer support and practical support. CONCLUSION: Both patient- and healthcare-related factors play a role in why IBD patients do (not) seek fatigue-related care. Our findings emphasise the importance of active screening and discussion of fatigue, using a holistic and person-centred approach to treat fatigue. IMPLICATIONS: This study contributes to the understanding of IBD patients' facilitators and barriers for seeking care for fatigue and their care needs. Moreover, results can inform nurses and physicians about ways to optimise the offer and uptake of fatigue-related care, and the development of interventions that fit patients' needs. Results also provide implications for the treatment of fatigue in other chronic (inflammatory) conditions. IMPACT: The current results can inform nurses and physicians about ways to optimise the offer and uptake of fatigue-related care, and the development of interventions that fit the needs of patients with IBD. An increase in the uptake of effective and acceptable interventions can improve patients' health and well-being. REPORTING METHOD: Findings were reported following the consolidated criteria for reporting qualitative research (COREQ). PATIENT OR PUBLIC CONTRIBUTION: No patients, service users or members of the public were involved in this study. The study focused on patients' experiences with fatigue-related care and their needs
Integral aspects of Fourier duality for abelian varieties
No full textContains fulltext :
322647.pdf (Publisher’s version ) (Open Access
Anonymized GPS tracks
No full textItem does not contain fulltextSpatially anonymized GPS tracks for manuscript: "Wild canids and felids differ in memory-related use of travel routes." V2 is the correct version to use in replicated or further analyses