Legal age limits in accessing donor information: experiences of donor-conceived people, parents, sperm donors and counsellors.

RESEARCH QUESTION: What are the lived experiences of donor-conceived people, parents, sperm donors and counsellors related to legal age limits on accessing donor information in the Netherlands? DESIGN: A phenomenological study was carried out that included 20 donor-conceived individuals, 15 parents, 6 sperm donors and 5 counsellors. Data were collected through online qualitative in-depth interviews and focus groups. The data were analysed using Dahlberg's Reflective Lifeworld Approach. RESULTS: The results show how: (i) age limits create challenges related to dependency, autonomy and loyalty to parents; (ii) donor information can be important for identity development, which looks different at different ages; (iii) inaccessible information can lead to unfair loss and may be perceived as negative; (iv) relational stability provides a good foundation for dealing with the (in)accessibility of donor information; (v) procedural barriers and age limits increase the inaccessibility of donor information; and (vi) comprehensive counselling is desired for donor-conceived individuals, parents and donors. CONCLUSIONS: This study shows that legal age limits on accessing donor information can lead to several negative consequences. The age limits focus on one individual, which is not appropriate for questions about ancestry that always pertain to a relational network. Counselling should be tailored to the child's needs, and the child's family should be involved. Furthermore, the donor should receive independent counselling.

Cardiovascular risk assessment in women: which women are suited for menopausal hormone therapy?

Individual risk assessment for atherosclerotic cardiovascular disease is important for safe menopausal hormone prescription. Besides the traditional risk factors, female-specific risk variables related to pregnancy and gynecologic conditions importantly contribute to a more tailored risk assessment in women at middle age. Of these, prior pre-eclampsia/HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome and early spontaneous menopause (<40 years) seem to be the strongest adverse risk variables. Concomitant inflammatory disorders should also be taken into account. Adding a coronary artery calcium score with a computed tomography scan to risk assessment has a high predictive value for future cardiovascular events. This should be considered to discriminate between low-risk and high-risk women when uncertainty exists. In women at intermediate risk, menopausal hormone therapy can be easily combined with preventive medication if cardiovascular risk factors are present. In women at higher risk who have severe disabling vasomotor symptoms, a lower dosage of hormone therapy can be considered in good collaboration between the gynecologist and the cardiologist/vascular specialist.

Gaussian Process-based prediction of memory performance and biomarker status in ageing and Alzheimer's disease-A systematic model evaluation.

Neuroimaging markers based on Magnetic Resonance Imaging (MRI) combined with various other measures (such as genetic covariates, biomarkers, vascular risk factors, neuropsychological tests etc.) might provide useful predictions of clinical outcomes during the progression towards Alzheimer's disease (AD). The use of multiple features in predictive frameworks for clinical outcomes has become increasingly prevalent in AD research. However, many studies do not focus on systematically and accurately evaluating combinations of multiple input features. Hence, the aim of the present work is to explore and assess optimal combinations of various features for MR-based prediction of (1) cognitive status and (2) biomarker positivity with a multi-kernel learning Gaussian process framework. The explored features and parameters included (A) combinations of brain tissues, modulation, smoothing, and image resolution; (B) incorporating demographics & clinical covariates; (C) the impact of the size of the training data set; (D) the influence of dimensionality reduction and the choice of kernel types. The approach was tested in a large German cohort including 959 subjects from the multicentric longitudinal study of cognitive impairment and dementia (DELCODE). Our evaluation suggests the best prediction of memory performance was obtained for a combination of neuroimaging markers, demographics, genetic information (ApoE4) and CSF biomarkers explaining 57% of outcome variance in out-of-sample predictions. The highest performance for Aß42/40 status classification was achieved for a combination of demographics, ApoE4, and a memory score while usage of structural MRI further improved the classification of individual patient's pTau status.

Design and rationale of the NetherLands registry of invasive Coronary vasomotor Function Testing (NL-CFT).

BACKGROUND: Angina without angiographic evidence of obstructive coronary artery disease (ANOCA) is a highly prevalent condition with insufficient pathophysiological knowledge and lack of evidence-based medical therapies. This affects ANOCA patients prognosis, their healthcare utilization and quality of life. In current guidelines, performing a coronary function test (CFT) is recommended to identify a specific vasomotor dysfunction endotype. The NetherLands registry of invasive Coronary vasomotor Function testing (NL-CFT) has been designed to collect data on ANOCA patients undergoing CFT in the Netherlands. METHODS: The NL-CFT is a web-based, prospective, observational registry including all consecutive ANOCA patients undergoing clinically indicated CFT in participating centers throughout the Netherlands. Data on medical history, procedural data and (patient reported) outcomes are gathered. The implementation of a common CFT protocol in all participating hospitals promotes an equal diagnostic strategy and ensures representation of the entire ANOCA population. A CFT is performed after ruling out obstructive coronary artery disease. It comprises of both acetylcholine vasoreactivity testing as well as bolus thermodilution assessment of microvascular function. Optionally, continuous thermodilution or Doppler flow measurements can be performed. Participating centers can perform research using own data, or pooled data will be made available upon specific request via a secure digital research environment, after approval of a steering committee. CONCLUSION: NL-CFT will be an important registry by enabling both observational and registry based (randomized) clinical trials in ANOCA patients undergoing CFT.

[Deforming endonasal mass during pregnancy]. / Deformierende endonasale Raumforderung während der Schwangerschaft.

This article presents the case of a 33-year-old woman who consulted the authors' ENT clinic in the 39th week of pregnancy with recurrent epistaxis. A livid endonasal mass was found on the left side, subtotally displacing the nose and leading to deformation of the external nose. External biopsy provided no indications of malignancy. Postpartum CT of the paranasal sinuses revealed a mass destroying the cartilaginous nasal septum. Endoscopic resection of the finding was performed with preservation of the clinically sound nasal septal cartilage. Histopathological examination revealed a capillary hemangioma, which was classified as granuloma gravidarum due to its occurrence during pregnancy.

Lessons from 10 years' experience running the Fiom KID-DNA database, a voluntary DNA-linking register for donor-conceived people and donors in The Netherlands.

Worldwide, there is increasing acknowledgment of the importance of getting access to ancestry information. More and more countries facilitate access to this information through law changes and voluntary contact-services. In the Netherlands, the state-funded Fiom KID-DNA database was established in 2010 to facilitate information and/or contact exchange between those people who are genetically related as a result of donor-assisted conception. By the end of 2021, 846 donors and 2355 donor-conceived people are registered in the database. For 25% of the donors a link was found with one or more donor-conceived people, and 39% of the donor-conceived people were linked to a donor-profile. Fiom offers support by professionally qualified staff throughout the entire process from registration to contact to donor-conceived people, donors and their relatives. During the period of more than 10 years several challenges emerged; how does a state-funded DNA database function in the area of commercial DNA databases?; what can be learned from the continuous growing donor-conceived half-siblings networks?; how to deal with malpractices from the past and how to cope with ageing donors?

Amphetamine or skin cream? The impact of the sampling site on the concentration of controlled substances: a case report.

This case report demonstrates the impact of different sampling sites on the quantification of narcotic substances. In 2020, officers secured a syringe containing a light-yellow paste-like substance, for which a drug pre-test indicated a positive result for amphetamine, inducing subsequent analyses of the sample by means of a gaschromatographic-mass spectrometric method (GC-MS) and liquid chromatography-(tandem) mass spectrometry (LC-MS/MS). Depending on the sample location, different results were obtained, with amphetamine not being detected in each sample. Amphetamine was particularly found at the outlet of the syringe, while amphetamine detection on the inside of the syringe at the plunger seal was only possible occasionally and, moreover, in lower concentrations. Based on this and with regard to the comparatively small amphetamine concentrations, contamination of the syringe (especially on the tip of the syringe) was assumed. Hence, the results strengthened the importance of the implication of different sampling sites, when either homogenization of the sample is not feasible or is not performed for reasons of plausibility checks concerning possible contamination of the sample.

Meeting multiple same-donor offspring: psychosocial challenges.

Debates regarding donor-conceived people's rights to genetic information have caused some jurisdictions to abolish donor anonymity. Moreover, voluntary services have been established whose primary focus is providing possibilities to find information about the donor. A less discussed consequence is that donor-conceived people also find information about donor half-siblings: people conceived through the same donor. In the recent climate of openness and online DNA tests, there is an increased chance of finding multiple donor half-siblings. This study explored how donor-conceived people experience meeting multiple same-donor offspring in a group setting. Second, the study investigated donor-conceived people's need for support when meeting multiple donor half-siblings. A qualitative approach was used. Nineteen donor-conceived offspring who participated in donor half-sibling network meetings were interviewed. Using a grounded theory approach three themes were identified regarding group aspects: (i) defining group membership; (ii) regulating closeness and distance; and (iii) managing group dynamics. Professional support needs in relation to these themes were also analysed. While establishing relationships between donor half-siblings are viewed as generally more beneficial than connecting with a donor, this study showed that these new relationships also come with their challenges, and counselling may need to be refined towards a more specific same donor-offspring relationships' framework.

Cardiometabolic health in premature ovarian insufficiency.

Premature ovarian insufficiency (POI) is an increasing public health problem with a prevalence now approaching 4%. POI results in adverse effects on the skeleton and central nervous system as well as disturbances of metabolic and cardiological factors that predispose to a major increased risk of cardiovascular disease (CVD). This article reviews the effects of the premature loss of ovarian function on lipids and lipoproteins, glucose and insulin metabolism, body composition, hemostasis and blood pressure, together with effects on the development of metabolic syndrome and diabetes mellitus. The article examines the effects of POI on vascular endothelial function and inflammation that result in arterial disease, and reviews the effects of hormone replacement therapy (HRT) on these various metabolic processes and on cardiovascular outcomes. It is essential that women with POI receive hormonal treatment to help prevent the development of CVD, and that this treatment is continued at least until the normal age of menopause. It appears that HRT has a more favorable effect than the combined oral contraceptive, but larger clinical trials are needed to establish the optimal treatment. Other therapeutic measures may need to be added to correct existing metabolic abnormalities and, in particular, attention to lifestyle factors such as diet and exercise must be encouraged.

The Chilean socio-ethno-genomic cline.

Studies of the current Chilean population performed using classical genetic markers have established that the Chilean population originated primarily from the admixture of European people, particularly Spaniards, and Amerindians. A socioeconomic-ethno-genetic cline was established soon after the conquest. Spaniards born in Spain or Chile occupied the highest Socioeconomic Strata, while Amerindians belonged to the lowest. The intermediate strata consisted of people with different degrees of ethnic admixture; the larger the European admixture, the higher the Socioeconomic Level. The present study of molecular genomic markers sought to calculate the percentage of Amerindian admixture and revealed a finer distribution of this cline, as well as differences between two Amerindian groups: Aymara and Mapuche. The use of two socioeconomic classifications - Class and Socioeconomic Level - reveals important differences. Furthermore, Self-reported Ethnicity (self-assignment to an ethnic group) and Self-reported Ancestry (self-recognition of Amerindian ancestors) show variations and differing relationships between socioeconomic classifications and genomic Amerindian Admixture. These data constitute a valuable input for the formulation of public healthcare policy and show that the notions of Ethnicity, Socioeconomic Strata and Class should always be a consideration in policy development.

A generic curriculum development model for the biomedical physics component of the educational and training programmes of the non-physics healthcare professions.

The objective of the study was the construction of a generic curriculum development model for the use of biomedical physics (BMP) educators teaching the non-physics healthcare professions (HCP) in Europe. A comprehensive, qualitative cross-sectional Europe-wide survey of the curricula delivered by BMP in Faculties of Medicine and Health Sciences (FMHS) was carried out. Curricular content was collected from faculty web-sites, curricular documents and textbooks. The survey data was supplemented with semi-structured interviews and direct observation during onsite visits. The number of faculties studied was 118 from 67 universities spread all over Europe, whilst the number of onsite visits/interviews was 15 (geographically distributed as follows: Eastern Europe 6, North Western Europe 5, and South Western Europe 4). EU legislation, recommendations by European national medical councils, educational benchmark statements by higher education quality assurance agencies, research journals concerning HCP education and other documents relevant to standards in clinical practice and undergraduate education were also analyzed. Best practices and BMP learning outcomes were elicited from the curricular materials, interviews and documentation and these were subsequently used to construct the curriculum development model. A structured, comprehensive BMP learning outcomes inventory was designed in the format required by the European Qualifications Framework (EQF). The structures of the inventory and curriculum development model make them ideally suited for use by BMP involved in European curriculum development initiatives for the HCP.

Time-of-flight mass spectrometry of particle emission during irradiation with slow, highly charged ions.

We describe a setup for the analysis of secondary ions and neutrals emitted from solid surfaces and two-dimensional materials during irradiation with highly charged ions. The ultrahigh vacuum setup consists of an electron beam ion source to produce bunches of ions with various charge states q (e.g., Xe1+-Xe46+) and thus potential energies, a deceleration/acceleration section to tune the kinetic energy of the ions in the range of 5 keV to 20 × q keV, a sample stage for laser-cleaning and positioning of freestanding as well as supported samples, a pulsed excimer laser for post-ionization of sputtered neutrals, and a reflectron type time-of-flight mass spectrometer, enabling us to analyze mass and velocity distributions of the emitted particles. With our setup, contributions from potential and kinetic energy deposition can be studied independently of each other. Charge dependent experiments conducted at a constant kinetic energy show a clear threshold for the emission of secondary ions from SrTiO3. Data taken with the same projectile charge state, but at a different kinetic energy, reveal a difference in the ratio of emitted particles from MoS2. In addition, first results are presented, demonstrating how velocity distributions can be measured with the new setup.

Diagnostic approach in patients with angina and no obstructive coronary artery disease: emphasising the role of the coronary function test.

BACKGROUND: Many patients with angina do not have obstructive coronary artery disease (CAD), also referred to as "Ischaemia with No Obstructive Coronary Arteries" (INOCA). Coronary vascular dysfunction is the underlying cause of this ischaemic heart disease in as much as 59-89% of these patients, including the endotypes of coronary microvascular dysfunction and epicardial coronary vasospasm. Currently, a coronary function test (CFT) is the only comprehensive diagnostic modality to evaluate all endotypes of coronary vascular dysfunction in patients with INOCA. OBJECTIVE: In this paper we discuss the relevance of performing a CFT, provide considerations for patient selection, and present an overview of the procedure and its safety. METHODS: We reviewed the latest published data, guidelines and consensus documents, combined with a discussion of novel original data, to present this point of view. RESULTS: The use of a CFT could lead to a more accurate and timely diagnosis of vascular dysfunction, identifies patients at risk for cardiovascular events, and enables stratified treatment which improves symptoms and quality of life. Current guidelines recommend considering a CFT in patients with INOCA and persistent symptoms. The safety of the procedure is comparable to that of a regular coronary angiography with physiological measurements. Non-invasive alternatives have limited diagnostic accuracy for the identification of coronary vascular dysfunction in patients with INOCA, and a regular coronary angiography and/or coronary computed tomography scan cannot establish the diagnosis. CONCLUSIONS: A complete CFT, including acetylcholine and adenosine tests, should be considered in patients with INOCA.

Inducible expression of human C9ORF72 36x G4C2 hexanucleotide repeats is sufficient to cause RAN translation and rapid muscular atrophy in mice.

The hexanucleotide G4C2 repeat expansion in the first intron of the C9ORF72 gene explains the majority of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) cases. Numerous studies have indicated the toxicity of dipeptide repeats (DPRs) which are produced via repeat-associated non-AUG (RAN) translation from the repeat expansion and accumulate in the brain of C9FTD/ALS patients. Mouse models expressing the human C9ORF72 repeat and/or DPRs show variable pathological, functional, and behavioral characteristics of FTD and ALS. Here, we report a new Tet-on inducible mouse model that expresses 36x pure G4C2 repeats with 100bp upstream and downstream human flanking regions. Brain specific expression causes the formation of sporadic sense DPRs aggregates upon 6 months dox induction but no apparent neurodegeneration. Expression in the rest of the body evokes abundant sense DPRs in multiple organs, leading to weight loss, neuromuscular junction disruption, myopathy, and a locomotor phenotype within the time frame of four weeks. We did not observe any RNA foci or pTDP-43 pathology. Accumulation of DPRs and the myopathy phenotype could be prevented when 36x G4C2 repeat expression was stopped after 1 week. After 2 weeks of expression, the phenotype could not be reversed, even though DPR levels were reduced. In conclusion, expression of 36x pure G4C2 repeats including 100bp human flanking regions is sufficient for RAN translation of sense DPRs and evokes a functional locomotor phenotype. Our inducible mouse model suggests early diagnosis and treatment are important for C9FTD/ALS patients.

Consensus statement from the international consensus meeting on post-traumatic cranioplasty.

BACKGROUND: Due to the lack of high-quality evidence which has hindered the development of evidence-based guidelines, there is a need to provide general guidance on cranioplasty (CP) following traumatic brain injury (TBI), as well as identify areas of ongoing uncertainty via a consensus-based approach. METHODS: The international consensus meeting on post-traumatic CP was held during the International Conference on Recent Advances in Neurotraumatology (ICRAN), in Naples, Italy, in June 2018. This meeting was endorsed by the Neurotrauma Committee of the World Federation of Neurosurgical Societies (WFNS), the NIHR Global Health Research Group on Neurotrauma, and several other neurotrauma organizations. Discussions and voting were organized around 5 pre-specified themes: (1) indications and technique, (2) materials, (3) timing, (4) hydrocephalus, and (5) paediatric CP. RESULTS: The participants discussed published evidence on each topic and proposed consensus statements, which were subject to ratification using anonymous real-time voting. Statements required an agreement threshold of more than 70% for inclusion in the final recommendations. CONCLUSIONS: This document is the first set of practical consensus-based clinical recommendations on post-traumatic CP, focusing on timing, materials, complications, and surgical procedures. Future research directions are also presented.

Anonymous Dutch sperm donors releasing their identity.

This study examined the motivations of anonymous Dutch sperm donors to release their identity. It aimed to increase knowledge and encourage donors to become identifiable through a more informed decision, allowing more donor-conceived persons to contact their donors. Since 2010, anonymous sperm donors in the Netherlands can register in the Fiom KID-DNA Database developed by Fiom and Canisius Wilhelmina Hospital (CWZ). An online survey was sent to donors who registered in the database (May 2015-August 2017). A total of 179 male respondents participated in this study. The motives of most donors to register in the database were child-oriented: donors believe that their offspring are entitled to their physical and social details and/or they want to give their offspring the chance to contact them. Other motives are donor-oriented, such as the curiosity about the number of offspring, their well-being and the desire to establish contact. This research showed that, to encourage anonymous donors to release their identity, one should focus on providing information about the existence of DNA databases. As well as increasing the donor's awareness of problems donor-conceived persons can experience by the lack of knowledge about their descent, answering questions and concerns from donors, and exploring the curiosity about their offspring.

[Industrial wind turbine noise: the association with human health]. / Geluid van industriële windturbines.

Climate targets will provide the Netherlands with more and higher industrial wind turbines that produce various 'side effects', including noise pollution and annoyance. Especially low-frequency noise and infrasonic vibrations can be detected more than 10 km away. In neighbouring residential areas, long-term exposure, especially at night, leads to sleep disturbances, with secondary symptoms, that may be associated with, for example, delay in cognitive development of children. More research is needed.

Breakfast partly restores the anti-inflammatory function of high-density lipoproteins from patients with type 2 diabetes mellitus.

Background and aims: High-density lipoproteins (HDL) of patients with type 2 diabetes mellitus (T2DM) have impaired anti-inflammatory activities. The anti-inflammatory activity of HDL has been determined ex vivo after isolation by different methods from blood mostly obtained after overnight fasting. We first determined the effect of the HDL isolation method, and subsequently the effect of food intake on the anti-inflammatory function of HDL from T2DM patients. Methods: Blood was collected from healthy controls and T2DM patients after an overnight fast, and from T2DM patients 3 h after breakfast (n = 17 each). HDL was isolated by a two-step density gradient ultracentrifugation in iodixanol (HDLDGUC2), by sequential salt density flotation (HDLSEQ) or by PEG precipitation (HDLPEG). The anti-inflammatory function of HDL was determined by the reduction of the TNFα-induced expression of VCAM-1 in human coronary artery endothelial cells (HCAEC) and retinal endothelial cells (REC). Results: HDL isolated by the three different methods from healthy controls inhibited TNFα-induced VCAM-1 expression in HCAEC. With apoA-I at 0.7 µM, HDLDGUC2 and HDLSEQ were similarly effective (16% versus 14% reduction; n = 3; p > 0.05) but less effective than HDLPEG (28%, p < 0.05). Since ultracentrifugation removes most of the unbound plasma proteins, we used HDLDGUC2 for further experiments. With apoA-I at 3.2 µM, HDL from fasting healthy controls and T2DM patients reduced TNFα-induced VCAM-1 expression in HCAEC by 58 ± 13% and 51 ± 20%, respectively (p = 0.35), and in REC by 42 ± 13% and 25 ± 18%, respectively (p < 0.05). Compared to preprandial HDL, postprandial HDL from T2DM patients reduced VCAM-1 expression by 56 ± 16% (paired test: p < 0.001) in HCAEC and by 34 ± 13% (paired test: p < 0.05) in REC. Conclusions: The ex vivo anti-inflammatory activity of HDL is affected by the HDL isolation method. Two-step ultracentrifugation in an iodixanol gradient is a suitable method for HDL isolation when testing HDL anti-inflammatory function. The anti-inflammatory activity of HDL from overnight fasted T2DM patients is significantly impaired in REC but not in HCAEC. The anti-inflammatory function of HDL is partly restored by food intake.

Ischaemia with no obstructive coronary arteries.

Ischaemia with no obstructive coronary arteries (INOCA) is a common ischaemic heart disease with a female preponderance, mostly due to underlying coronary vascular dysfunction comprising coronary microvascular dysfunction and/or epicardial coronary vasospasm. Since standard ischaemia detection tests and coronary angiograms are not suitable to diagnose coronary vascular dysfunction, INOCA is often overlooked in current cardiology practice. Future research, including large outcome trials, is much awaited. Yet, adequate diagnosis is possible and treatment options are available and vital to reduce symptoms and most probably improve cardiovascular prognosis. This review intends to give a brief overview of the clinical presentation, underlying pathophysiology, and the diagnostic and treatment options in patients with suspected INOCA.

Psychological and clinical characteristics of female patients with spontaneous coronary artery dissection.

AIMS: Spontaneous coronary artery dissection (SCAD) is increasingly recognised as a cause of myocardial infarction, but psychological characteristics of patients with SCAD have not yet been extensively investigated. We assessed the prevalence of a broad range of psychological and clinical factors, and their inter-relationships in patients with a history of SCAD. Furthermore, we investigated whether specific clusters of patients with SCAD can be identified. METHODS: Participants were recruited between March and May 2019 from a Dutch SCAD database and completed online questionnaires. Clinical information was verified by review of medical records. Participants were predominantly female (172/183; 94%). Analyses focused on the 172 female patients (mean age 52.0 ± 7.5 years, 37% postmenopausal). RESULTS: The most common comorbidities of SCAD were migraine (52%), fibromuscular dysplasia (FMD; 29%), chronic pain (29%), and tinnitus (28%). Six women (3%) had pregnancy-associated SCAD. Traditional cardiovascular risk factors were rare (<10%), except for hypertension (31%). Psychological assessment indicated high levels of perceived stress (PSS-10 ≥14; 50%), fatigue (FAS-10 ≥22; 56%), and a frequent history of burnout (25%). The prevalence of depression (9%) and anxiety (12%) was relatively low. Three clusters were identified: (A) FMD and chronic non-ischaemic conditions (tinnitus, chronic pain, and irritable bowel syndrome); (B) migraine; and (C) none of these conditions. CONCLUSION: This study shows that perceived stress and fatigue are common in patients with SCAD, in addition to prevalent comorbid FMD, migraine, tinnitus, and non-ischaemic pain conditions. These factors may add to developing tailored rehabilitation programmes for patients with SCAD.