391 research outputs found
Early-stage macroporosity enhancement in calcium phosphate cements by inclusion of poly(N-vinylpyrrolidone) particles as a porogen
The incorporation of poly(DL-lactic-co-glycolic acid) (PLGA) particles into calcium phosphate cements (CPCs) is an effective strategy to enhance CPC macroporosity and degradation. However, bone regeneration is hindered until hydrolytic PLGA degradation starts a few weeks after implantation. Additionally, CPC and CPC/PLGA injectability and cohesion are suboptimal. In the current study, poly(N-vinylpyrrolidone) (PVP), a water-soluble polymer, was incorporated as a porogen in CPC and CPC/PLGA composites to enhance handling properties and early-stage macroporosity formation. Further, the effect of PVP molecular weight (Mw) and particle size was studied. The results showed that PVP incorporation increased both injectability and cohesion of the CPC pastes, especially with addition of high Mw PVP. Moreover, the in vitro degradation studies revealed that incorporation of PVP induced an initial mass loss during the first week of incubation. In combination with PLGA, small PVP particles induced a higher mass loss at an early stage than large PVP particles, but this effect was no longer apparent after 4 weeks of incubation. In contrast, the incorporation of low Mw PVP had a stronger effect on in vitro degradation in the long term compared to high Mw. Finally, the presence of PLGA porogens appeared to be necessary for adequate CPC degradation.Peer ReviewedPostprint (published version
Preimplantation genetic testing for Neurofibromatosis type 1:more than 20 years of clinical experience
Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder that affects the skin and the nervous system. The condition is completely penetrant with extreme clinical variability, resulting in unpredictable manifestations in affected offspring, complicating reproductive decision-making. One of the reproductive options to prevent the birth of affected offspring is preimplantation genetic testing (PGT). We performed a retrospective review of the medical files of all couples (nâ=â140) referred to the Dutch PGT expert center with the indication NF1 between January 1997 and January 2020. Of the couples considering PGT, 43 opted out and 15 were not eligible because of failure to identify the underlying genetic defect or unmet criteria for in vitro fertilization (IVF) treatment. The remaining 82 couples proceeded with PGT. Fertility assessment prior to IVF treatment showed a higher percentage of male infertility in males affected with NF1 compared to the partners of affected females. Cardiac evaluations in women with NF1 showed no contraindications for IVF treatment or pregnancy. For 67 couples, 143 PGT cycles were performed. Complications of IVF treatment were not more prevalent in affected females compared to partners of affected males. The transfer of 174 (out of 295) unaffected embryos led to 42 ongoing pregnancies with a pregnancy rate of 24.1% per embryo transfer. There are no documented cases of misdiagnosis following PGT in this cohort. With these results, we aim to provide an overview of PGT for NF1 with regard to success rate and safety, to optimize reproductive counseling and PGT treatment for NF1 patients.</p
Effecten van hormoonverstorende stoffen op kikkers
Omdat de ontwikkeling van amfibieën sterk hormoon-gereguleerd is, is onderzocht in hoeverre de kikker een geschikte indicator is voor hormoonverstorende stoffen in het milieu. Hiertoe zijn in het laboratorium blootstellingstudies uitgevoerd met kikkerlarven en volwassen Rana kikkers, welke algemeen in Nederland voorkomen. Onderzocht is in hoeverre oestradiol (E2) en tetrachloordibenzo-p-dioxine (TCDD) de ontwikkeling, overleving, lichaams- en orgaangewichten, geslachtsorganen en -hormonen, en specifieke cytochroom P450 enzymen beïnvloeden. Ook is de onderlinge samenhang van deze ettectparameters bestudeerd. In een in-situ veldstudie zijn de overleving en ontwikkeling van larven van Rana Kikkers, die zijn uitgezet in de sterk verontreinigde Volgermeerpolder en een niet-verontreinigde referentielocatie, beschouwd. Naast dit alles zijn juveniele Rana kikkers gevangen uit beide locaties, waarin interne concentraties dioxine-achtige stoffen en activiteiten van specifieke cytochroom P450 enzymen zijn bepaald
Molecular Design of Light-Responsive Hydrogels, For in Situ Generation of Fast and Reversible Valves for Microfluidic Applications
Preconception Care in International Settings
Objectives: This literature review briefly describes international programs, policies, and activities related to preconception care and resulting pregnancy outcomes. Methods: Electronic databases were searched and findings supplemented with secondary references cited in the original articles as well as textbook chapters, declarations, reports, and recommendations. Results: Forty-two articles, book chapters, declarations, and other published materials were reviewed. Policies, programs, and recommendations related to preconceptional health promotion exist worldwide and comprise a readily identifiable component of historic and modern initiatives pertaining to women's health, reproductive freedom, and child survival. Conclusions: The integration of preconception care services within a larger maternal and child health continuum of care is well aligned with a prevention-based approach to enhancing global health
A clustering of heterozygous missense variants in the crucial chromatin modifier WDR5 defines a new neurodevelopmental disorder
WDR5 is a broadly studied, highly conserved key protein involved in a wide array of biological functions. Among these functions, WDR5 is a part of several protein complexes that affect gene regulation via post-translational modification of histones. We collected data from 11 unrelated individuals with six different rare de novo germline missense variants in WDR5; one identical variant was found in five individuals, and another variant in two individuals. All individuals had neurodevelopmental disorders including speech/language delays (N=11), intellectual disability (N=9), epilepsy (N=7) and autism spectrum disorder (N=4). Additional phenotypic features included abnormal growth parameters (N=7), heart anomalies (N=2) and hearing loss (N=2). Three-dimensional protein structures indicate that all the residues affected by these variants are located at the surface of one side of the WDR5 protein. It is predicted that five out of the six amino acid substitutions disrupt interactions of WDR5 with RbBP5 and/or KMT2A/C, as part of the COMPASS (complex proteins associated with Set1) family complexes. Our experimental approaches in Drosophila melanogaster and human cell lines show normal protein expression, localization and protein-protein interactions for all tested variants. These results, together with the clustering of variants in a specific region of WDR5 and the absence of truncating variants so far, suggest that dominant-negative or gain-of-function mechanisms might be at play. All in all, we define a neurodevelopmental disorder associated with missense variants in WDR5 and a broad range of features. This finding highlights the important role of genes encoding COMPASS family proteins in neurodevelopmental disorders
Clinical spectrum of SIX3-associated mutations in holoprosencephaly: correlation between genotype, phenotype and function
BACKGROUND: Holoprosencephaly (HPE) is the most common structural malformation of the human forebrain. There are several important HPE mutational target genes, including the transcription factor SIX3, which encodes an early regulator of Shh, Wnt, Bmp and Nodal signalling expressed in the developing forebrain and eyes of all vertebrates. OBJECTIVE: To characterise genetic and clinical findings in patients with SIX3 mutations. METHODS: Patients with HPE and their family members were tested for mutations in HPE-associated genes and the genetic and clinical findings, including those for additional cases found in the literature, were analysed. The results were correlated with a mutation-specific functional assay in zebrafish. RESULTS: In a cohort of patients (n = 800) with HPE, SIX3 mutations were found in 4.7% of probands and additional cases were found through testing of relatives. In total, 138 cases of HPE were identified, 59 of whom had not previously been clinically presented. Mutations in SIX3 result in more severe HPE than in other cases of non-chromosomal, non-syndromic HPE. An over-representation of severe HPE was found in patients whose mutations confer greater loss of function, as measured by the functional zebrafish assay. The gender ratio in this combined set of patients was 1.5:1 (F:M) and maternal inheritance was almost twice as common as paternal. About 14% of SIX3 mutations in probands occur de novo. There is a wide intrafamilial clinical range of features and classical penetrance is estimated to be at least 62%. CONCLUSIONS: Our data suggest that SIX3 mutations result in relatively severe HPE and that there is a genotype-phenotype correlation, as shown by functional studies using animal models
Social Marketing: Planning Before Conceiving Preconception Care
Social marketing approaches can help to shape the formation of and to create demand for preconception care services. This article describes four components of social marketing, often referred to as the 4 Pâs, that should be carefully researched and set in place before a national effort to launch and sustain preconception care services is pursued. First, the product or package of services must be defined and adapted using the latest in scientific and health care standards and must be based on consumer needs and desires. Second, the pricing of the services in financial or opportunity costs must be acceptable to the consumer, insurers, and health care service providers. Third, the promotion of benefits must be carefully crafted to reach and appeal to both consumers and providers. Fourth, the placement and availability of services in the marketplace must be researched and planned. With the application of market research practices that incorporate health behavior theories in their exploration of each component, consumer demand for preconception care can be generated, and providers can take preconception care to the market with confidence
- âŠ