Publications by authors named "Graaf L"

Objectives: Older adults with physical or cognitive disabilities may need to move to residential care facilities (RCFs). Some older adults smoke tobacco and become dependent on their care professionals to continue smoking. Care professionals need to balance an individual resident's quality of life and well-being with the health and safety of all residents and staff.

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Antisense technology demonstrates significant potential for addressing inherited brain diseases, with over a dozen products already available and numerous others in the development pipeline. The versatility of differentiating induced pluripotent stem cells (iPSCs) into nearly all neural cell types proves invaluable for comprehending the mechanisms behind neurological diseases, replicating cellular phenotypes, and advancing the testing and development of new therapies, including antisense oligonucleotide therapeutics. While delivering antisense oligonucleotides (ASOs) to human iPSC-based neuronal models has posed challenges, this study explores various delivery methods, including lipid-based transfection, gymnotic uptake, Ca-enhanced medium (CEM)-based delivery, and electroporation, in 2D and 3D hiPSC-derived neuronal models.

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Spinocerebellar Ataxia Type 7 (SCA7) is an autosomal dominantly inherited disorder, primarily characterized by cerebellar ataxia and visual loss. SCA7 is caused by a CAG repeat expansion in exon 3 of the ATXN7 gene. We generated human induced pluripotent stem cells (hiPSCs) from peripheral blood-derived erythroblasts from two SCA7 patients (LUMCi051-A,B and LUMCi052-A,B,C) using integration-free episomal vectors.

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Since 2014, the Agricultural Operator Exposure Model (AOEM) has been the harmonised European model used for estimating non-dietary operator exposure to pesticide. It is based on studies conducted by the pesticide companies and it features 13 different crops including non-agricultural areas such as amenity grasslands. The objective of this study was to compare the dermal exposure measured during a field study conducted in a non-agricultural area with the corresponding values estimated by the model AOEM.

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Precision Livestock Farming systems can help pig farmers prevent health and welfare issues around farrowing. Five sows were monitored in two field studies. A Sorama L642V sound camera, visualising sound sources as coloured spots using a 64-microphone array, and a Bascom XD10-4 security camera with a built-in microphone were used in a farrowing unit.

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Context: There is a lack of data on pesticide exposure levels during spraying with a knapsack, while it could have important implications for their users' health.

Methods: We assessed levels and determinants of exposure in 24 male private landscapers/gardeners and municipal workers in France in 2011. Actual dermal exposure to glyphosate was assessed with cotton undergarments and gloves, and a cotton coverall changed between mixing and spraying to assess the contribution of each phase and body area to overall contamination.

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Residential care facilities (RCFs) provide 24/7 care to older adults with cognitive and/or physical disabilities and aim to provide person-centered care (PCC). Maintaining residents' autonomy is important to provide PCC, for example, with shared decision-making (SDM). Residents are largely dependent on multiple stakeholders, which could jeopardize their autonomy, especially regarding unhealthy behaviors, such as smoking tobacco or drinking alcohol.

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Background: Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disease caused by a polyglutamine expansion in the ataxin-1 protein resulting in neuropathology including mutant ataxin-1 protein aggregation, aberrant neurodevelopment, and mitochondrial dysfunction.

Objectives: Identify SCA1-relevant phenotypes in patient-specific fibroblasts and SCA1 induced pluripotent stem cells (iPSCs) neuronal cultures.

Methods: SCA1 iPSCs were generated and differentiated into neuronal cultures.

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Cities attracting large numbers of tourists increasingly face crowding and public resistance to tourism growth. As a result, governments strive to spread tourists from the best-known attractions to less-visited locations to improve both residents' and tourists' quality of life. Evidence of success and best practices herein is largely anecdotal, and the effects on tourist experience are also unknown.

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Introduction: ADutch-type cerebral amyloid angiopathy (D-CAA) is a hereditary brain disorder caused by a point mutation in the amyloid precursor protein (APP) gene. The mutation is located within the amyloid beta (Aβ) domain of APP and leads to Aβ peptide accumulation in and around the cerebral vasculature. There lack of disease models to study the cellular and molecular pathological mechanisms of D-CAA together with the absence of a disease phenotype in vitro in overexpression cell models, as well as the limited availability of D-CAA animal models indicates the need for a D-CAA patient-derived model.

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Background: Alcohol and tobacco use could cause health problems in older adults. Older adults who become in need of 24/7 care due to physical and/or neurological disabilities may need to move to a Residential Care Facility (RCF). RCFs aim to provide person-centred care (PCC) to enhance quality of life (QoL) of residents.

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Introduction: Knowledge on the health of greenspace workers is scarce, even though they are exposed to many occupational hazards. The aim of this study was to analyze mortality by cause, prevalence of some non-cancer diseases, and incidence of the main cancers among greenspace workers.

Methods: A sub-cohort of greenspace workers was formed within the AGRICAN cohort.

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Context: The greenspace sector includes a broad range of occupations: gardeners, landscapers, municipal workers, maintenance operators of public facilities, golf-course employees and other sports facilities, horticulturists, plant and tree nursery workers etc. The health impact of occupational pesticide exposure has mainly been studied among farmers. Other professionals such as greenspace workers are also extremely exposed, presenting specific exposure features (practices, types of pesticide used).

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Dutch-type cerebral amyloid angiopathy (D-CAA) is a monogenic form of cerebral amyloid angiopathy and is inherited in an autosomal dominant manner. The disease is caused by a point mutation in exon 17 of the amyloid precursor protein () gene that leads to an amino acid substitution at codon 693. The mutation is located within the amyloid beta (Aβ) domain of APP, and leads to accumulation of toxic Aβ peptide in and around the cerebral vasculature.

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Background: The etiology of the central nervous system (CNS) tumors remains largely unknown. The role of pesticide exposure has been suggested by several epidemiological studies, but with no definitive conclusion.

Objective: To analyze associations between occupational pesticide exposure and primary CNS tumors in adults in the CERENAT study.

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Objectives: Abiraterone acetate is registered for the treatment of metastatic castration-sensitive and resistant prostate cancer (mCRPC). Treatment outcome is associated with plasma trough concentrations (C) of abiraterone. Patients with a plasma C below the target of 8.

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Huntington disease (HD) is an autosomal dominant, neurodegenerative disease caused by a CAG repeat expansion within the coding sequence of the HTT gene, resulting in a highly toxic protein with an expanded polyglutamine stretch that forms typical protein aggregates throughout the brain. We generated human induced pluripotent stem cells (hiPSCs) from two HD patients using non-integrating Sendai virus (SeV). The hiPSCs display a normal karyotype, express all pluripotency markers, have the same CAG repeat expansion as the original fibroblasts and are able to differentiate into the three germ layers in vitro.

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In severe forms of cerebral amyloid angiopathy (CAA) pathology, vascular calcification has been observed in the cerebral cortex, both in vivo on MRI and CT, and post-mortem using histopathology. However, the pathomechanisms leading to calcification of CAA-laden arteries are unknown. Therefore, we investigated the correlation between calcification of cortical arterioles and several potential modulators of vascular calcification using immunohistochemistry in a unique collection of brain material of patients with a hereditary form of CAA, namely hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D or D-CAA).

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Hereditary Cerebral Hemorrhage with Amyloidosis-Dutch type (HCHWA-D) is an autosomal dominant hereditary disease caused by a point mutation in exon 17 of the APP gene. We generated human induced pluripotent stem cells (hiPSCs) from a symptomatic HCHWA-D patient by using non-integrating Sendai virus (SeV). The newly generated hiPSCs express all pluripotency markers, have a normal karyotype, carry the Dutch mutation, can differentiate in the three germ layers in vitro and are SeV free.

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This article explores how comprehensive cancer control plans and partnerships have evolved, over the past 20 years, to meet the ever-changing environment of cancer prevention and control. This evolution has resulted in plans that take a more focused approach in identifying cancer-related priorities and coalitions with structures that have been redesigned to better engage a more wide-ranging group of partners to help address the priorities. Presented in this paper are examples from three states that describe how recognizing the need for change has led to improved processes in updating a cancer plan; strengthened and more diverse partnerships; and coalition sustainment by leveraging and maximizing resources.

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Background and Purpose- Previous studies of symptomatic and asymptomatic hereditary cerebral amyloid angiopathy (CAA) patients offered the possibility to study the radiological manifestations of CAA in the early stages of the disease. Recently, a striped cortex, observable as hypointense lines perpendicular to the pial surface on T-weighted 7T magnetic resonance imaging (MRI), was detected in 40% of the symptomatic hereditary CAA patients. However, the origin of these MRI contrast changes is unknown.

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The value of iron-based MRI changes for the diagnosis and staging of Alzheimer's disease (AD) depends on an association between cortical iron accumulation and AD pathology. Therefore, this study determined the cortical distribution pattern of MRI contrast changes in cortical regions selected based on the known distribution pattern of tau pathology and investigated whether MRI contrast changes reflect the underlying AD pathology in the different lobes. T2*-weighted MRI was performed on postmortem cortical tissue of controls, late-onset AD (LOAD), and early-onset AD (EOAD) followed by histology and correlation analyses.

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This review on magnetic resonance elastography (MRE) of the breast provides an overview of available literature and describes current developments in the field of breast MRE, including new transducer technology for data acquisition and multi-frequency-derived power-law behaviour of tissue. Moreover, we discuss the future potential of breast MRE, which goes beyond its original application as an additional tool in differentiating benign from malignant breast lesions. These areas of ongoing and future research include MRE for pre-operative tumour delineation, staging, monitoring and predicting response to treatment, as well as prediction of the metastatic potential of primary tumours.

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