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1.
Nature ; 621(7977): 56-59, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37364766

RESUMO

Forty years ago, it was proposed that gas-phase organic chemistry in the interstellar medium can be initiated by the methyl cation CH3+ (refs. 1-3), but so far it has not been observed outside the Solar System4,5. Alternative routes involving processes on grain surfaces have been invoked6,7. Here we report James Webb Space Telescope observations of CH3+ in a protoplanetary disk in the Orion star-forming region. We find that gas-phase organic chemistry is activated by ultraviolet irradiation.

2.
Acc Chem Res ; 54(8): 1921-1933, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33780617

RESUMO

ConspectusPolycyclic aromatic hydrocarbon molecules (PAHs) are ubiquitously present at high abundances in the Universe. They are detected through their infrared (IR) fluorescence UV pumped by nearby massive stars. Hence, their infrared emission is used to determine the star formation rate in galaxies, one of the key indicators for understanding the evolution of galaxies. Together with fullerenes, PAHs are the largest molecules found in space. They significantly partake in a variety of physical and chemical processes in space, influencing star and planet formation as well as galaxy evolution.Since the IR features from PAHs originate from chemical bonds involving only nearest neighbor atoms, they have only a weak dependence on the size and structure of the molecule, and it is therefore not possible to identify the individual PAH molecules that make up the cosmic PAH family. This strongly hampers the interpretation of their astronomical fingerprints. Despite the lack of identification, constraints can be set on the characteristics of the cosmic PAH family thanks to a joint effort of astronomers, physicists, and chemists.This Account presents the spectroscopic properties of the cosmic PAH emission as well as the intrinsic spectroscopic properties of PAHs and astronomical modeling of the PAH evolution required for the interpretation of the cosmic PAH characteristics. We discuss the observed spectral signatures tracing PAH properties such as charge, size, and structure and highlight the related challenges. We discuss the recent success of anharmonic calculations of PAH infrared absorption and emission spectra and outline the path forward. Finally, we illustrate the importance of models on PAH processing for the interpretation of the astronomical data in terms of the charge balance and PAH destruction.Throughout this Account, we emphasize that huge progress is on the horizon on the astronomical front. Indeed, the world is eagerly awaiting the launch of the James Webb Space Telescope (JWST). With its incredible improvement in spatial resolution, combined with its complete spectral coverage of the PAH infrared emission bands at medium spectral resolution and superb sensitivity, the JWST will revolutionize PAH research. Previous observations could only present spectra averaged over regions with vastly different properties, thus greatly confusing their interpretation. The amazing spatial resolution of JWST will disentangle these different regions. This will allow us to quantify precisely how PAHs are modified by the physical conditions of their host environment and thus trace how PAHs evolve across space. However, this will only be achieved when the necessary (and still missing) fundamental properties of PAHs, outlined in this Account, are known. We strongly encourage you to join this effort.

3.
Brain ; 142(4): 867-884, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30879067

RESUMO

Recessive mutations in RTTN, encoding the protein rotatin, were originally identified as cause of polymicrogyria, a cortical malformation. With time, a wide variety of other brain malformations has been ascribed to RTTN mutations, including primary microcephaly. Rotatin is a centrosomal protein possibly involved in centriolar elongation and ciliogenesis. However, the function of rotatin in brain development is largely unknown and the molecular disease mechanism underlying cortical malformations has not yet been elucidated. We performed both clinical and cell biological studies, aimed at clarifying rotatin function and pathogenesis. Review of the 23 published and five unpublished clinical cases and genomic mutations, including the effect of novel deep intronic pathogenic mutations on RTTN transcripts, allowed us to extrapolate the core phenotype, consisting of intellectual disability, short stature, microcephaly, lissencephaly, periventricular heterotopia, polymicrogyria and other malformations. We show that the severity of the phenotype is related to residual function of the protein, not only the level of mRNA expression. Skin fibroblasts from eight affected individuals were studied by high resolution immunomicroscopy and flow cytometry, in parallel with in vitro expression of RTTN in HEK293T cells. We demonstrate that rotatin regulates different phases of the cell cycle and is mislocalized in affected individuals. Mutant cells showed consistent and severe mitotic failure with centrosome amplification and multipolar spindle formation, leading to aneuploidy and apoptosis, which could relate to depletion of neuronal progenitors often observed in microcephaly. We confirmed the role of rotatin in functional and structural maintenance of primary cilia and determined that the protein localized not only to the basal body, but also to the axoneme, proving the functional interconnectivity between ciliogenesis and cell cycle progression. Proteomics analysis of both native and exogenous rotatin uncovered that rotatin interacts with the neuronal (non-muscle) myosin heavy chain subunits, motors of nucleokinesis during neuronal migration, and in human induced pluripotent stem cell-derived bipolar mature neurons rotatin localizes at the centrosome in the leading edge. This illustrates the role of rotatin in neuronal migration. These different functions of rotatin explain why RTTN mutations can lead to heterogeneous cerebral malformations, both related to proliferation and migration defects.


Assuntos
Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/fisiologia , Adulto , Encéfalo/patologia , Proteínas de Transporte/genética , Ciclo Celular/fisiologia , Cílios/metabolismo , Feminino , Estudos de Associação Genética/métodos , Células HEK293 , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Lactente , Recém-Nascido , Masculino , Malformações do Desenvolvimento Cortical/genética , Malformações do Desenvolvimento Cortical/metabolismo , Microcefalia/genética , Mutação , Malformações do Sistema Nervoso/genética , Polimicrogiria/etiologia , Polimicrogiria/patologia
4.
Neurogenetics ; 18(2): 73-79, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27747449

RESUMO

Kinesins play a critical role in the organization and dynamics of the microtubule cytoskeleton, making them central players in neuronal proliferation, neuronal migration, and postmigrational development. Recently, KIF2A mutations were identified in cortical malformation syndromes associated with microcephaly. Here, we detected two de novo p.Ser317Asn and p.His321Pro mutations in KIF2A in two patients with lissencephaly and microcephaly. In parallel, we re-evaluated the two previously reported cases showing de novo mutations of the same residues. The identification of mutations only in the residues Ser317 and His321 suggests these are hotspots for de novo mutations. Both mutations lead to a classic form of lissencephaly, with a posterior to anterior gradient, almost indistinguishable from LIS1-related lissencephaly. However, three fourths of patients also showed variable congenital and postnatal microcephaly, up to -5 SD. Located in the motor domain of the KIF2A protein, the Ser317 and His321 alterations are expected to disrupt binding or hydrolysis of ATP and consequently the MT depolymerizing activity. This report also establishes that KIF2A mutations represent significant causes of classic lissencephaly with microcephaly.


Assuntos
Lissencefalias Clássicas e Heterotopias Subcorticais em Banda/genética , Cinesinas/genética , Mutação de Sentido Incorreto , Adolescente , Análise Mutacional de DNA , Feminino , Frequência do Gene , Humanos , Lactente , Lisencefalia/genética , Masculino , Polimorfismo de Nucleotídeo Único
5.
Genet Med ; 19(1): 45-52, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27195816

RESUMO

PURPOSE: Truncating mutations in the maternally imprinted, paternally expressed gene MAGEL2, which is located in the Prader-Willi critical region 15q11-13, have recently been reported to cause Schaaf-Yang syndrome, a Prader-Willi-like disease that manifests as developmental delay/intellectual disability, hypotonia, feeding difficulties, and autism spectrum disorder. The causality of the reported variants in the context of the patients' phenotypes was questioned, as MAGEL2 whole-gene deletions seem to cause little or no clinical phenotype. METHODS: Here we report a total of 18 newly identified individuals with Schaaf-Yang syndrome from 14 families, including 1 family with 3 individuals found to be affected with a truncating variant of MAGEL2, 11 individuals who are clinically affected but were not tested molecularly, and a presymptomatic fetal sibling carrying the pathogenic MAGEL2 variant. RESULTS: All cases harbor truncating mutations of MAGEL2, and nucleotides c.1990-1996 arise as a mutational hotspot, with 10 individuals and 1 fetus harboring a c.1996dupC (p.Q666fs) mutation and 2 fetuses harboring a c.1996delC (p.Q666fs) mutation. The phenotypic spectrum of Schaaf-Yang syndrome ranges from fetal akinesia to neurobehavioral disease and contractures of the small finger joints. CONCLUSION: This study provides strong evidence for the pathogenicity of truncating mutations of the paternal allele of MAGEL2, refines the associated clinical phenotypes, and highlights implications for genetic counseling for affected families.Genet Med 19 1, 45-52.


Assuntos
Transtorno do Espectro Autista/genética , Deficiências do Desenvolvimento/genética , Deficiência Intelectual/genética , Síndrome de Prader-Willi/genética , Proteínas/genética , Adolescente , Adulto , Transtorno do Espectro Autista/fisiopatologia , Criança , Pré-Escolar , Cromossomos Humanos Par 15 , Deficiências do Desenvolvimento/fisiopatologia , Feminino , Expressão Gênica , Impressão Genômica , Humanos , Lactente , Recém-Nascido , Deficiência Intelectual/fisiopatologia , Masculino , Mutação , Fenótipo , Síndrome de Prader-Willi/fisiopatologia
6.
Science ; 383(6686): 988-992, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38422128

RESUMO

Most low-mass stars form in stellar clusters that also contain massive stars, which are sources of far-ultraviolet (FUV) radiation. Theoretical models predict that this FUV radiation produces photodissociation regions (PDRs) on the surfaces of protoplanetary disks around low-mass stars, which affects planet formation within the disks. We report James Webb Space Telescope and Atacama Large Millimeter Array observations of a FUV-irradiated protoplanetary disk in the Orion Nebula. Emission lines are detected from the PDR; modeling their kinematics and excitation allowed us to constrain the physical conditions within the gas. We quantified the mass-loss rate induced by the FUV irradiation and found that it is sufficient to remove gas from the disk in less than a million years. This is rapid enough to affect giant planet formation in the disk.

7.
Ned Tijdschr Geneeskd ; 1672023 04 25.
Artigo em Holandês | MEDLINE | ID: mdl-37186238

RESUMO

In the Netherlands, 600 patients are diagnosed with tuberculosis annually, especially refugees and migrants. After arrival in the Netherlands, they are screened with a chest X-ray. However, 45% of patients present with extrapulmonary tuberculosis. We present a case of a 9 year old boy from Eritrea with tuberculosis of the central nervous system. When central nervous system tuberculosis is suspected, further diagnostic testing should be done and therapy started as soon as possible to prevent mortality and morbidity.


Assuntos
Refugiados , Migrantes , Tuberculose Extrapulmonar , Tuberculose , Masculino , Humanos , Criança , Tuberculose/diagnóstico , Eritreia , Sistema Nervoso Central
8.
Artigo em Inglês | MEDLINE | ID: mdl-36982084

RESUMO

OBJECTIVE: To assess problems faced by children with type 1 narcolepsy (NT1) at school and obtain insight into potential interventions for these problems. METHODS: We recruited children and adolescents with NT1 from three Dutch sleep-wake centers. Children, parents, and teachers completed questionnaires about school functioning, interventions in the classroom, global functioning (DISABKIDS), and depressive symptoms (CDI). RESULTS: Eighteen children (7-12 years) and thirty-seven adolescents (13-19 years) with NT1 were recruited. Teachers' most frequently reported school problems were concentration problems and fatigue (reported by about 60% in both children and adolescents). The most common arrangements at school were, for children, discussing school excursions (68%) and taking a nap at school (50%) and, for adolescents, a place to nap at school (75%) and discussing school excursions (71%). Regular naps at home on the weekend (children 71% and adolescents 73%) were more common than regular naps at school (children 24% and adolescents 59%). Only a minority of individuals used other interventions. School support by specialized school workers was associated with significantly more classroom interventions (3.5 versus 1.0 in children and 5.2 versus 4.1 in adolescents) and napping at school, but not with better global functioning, lower depressive symptom levels, or napping during the weekends. CONCLUSIONS: Children with NT1 have various problems at school, even after medical treatment. Interventions to help children with NT1 within the classroom do not seem to be fully implemented. School support was associated with the higher implementation of these interventions. Longitudinal studies are warranted to examine how interventions can be better implemented within the school.


Assuntos
Pessoal de Educação , Narcolepsia , Adolescente , Humanos , Criança , Narcolepsia/epidemiologia , Narcolepsia/terapia , Narcolepsia/complicações , Instituições Acadêmicas , Sono
9.
Hum Mutat ; 33(3): 561-71, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22213089

RESUMO

Ataxia-telangiectasia (A-T) is an autosomal recessive neurodegenerative disorder with multisystem involvement and cancer predisposition, caused by mutations in the A-T mutated (ATM) gene. To study genotype-phenotype correlations, we evaluated the clinical and laboratory data of 51 genetically proven A-T patients, and additionally measured ATM protein expression and kinase activity. Patients without ATM kinase activity showed the classical phenotype. The presence of ATM protein, correlated with slightly better immunological function. Residual kinase activity correlated with a milder and essentially different neurological phenotype, absence of telangiectasia, normal endocrine and pulmonary function, normal immunoglobulins, significantly lower X-ray hypersensitivity in lymphocytes, and extended lifespan. In these patients, cancer occurred later in life and generally consisted of solid instead of lymphoid malignancies. The genotypes of severely affected patients generally included truncating mutations resulting in total absence of ATM kinase activity, while patients with milder phenotypes harbored at least one missense or splice site mutation resulting in expression of ATM with some kinase activity. Overall, the phenotypic manifestations in A-T show a continuous spectrum from severe classical childhood-onset A-T to a relatively mild adult-onset disorder, depending on the presence of ATM protein and kinase activity. Each patient is left with a tremendously increased cancer risk.


Assuntos
Ataxia Telangiectasia/metabolismo , Ataxia Telangiectasia/patologia , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Adolescente , Adulto , Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia , Proteínas de Ciclo Celular/genética , Criança , Proteínas de Ligação a DNA/genética , Feminino , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Serina-Treonina Quinases/genética , Proteínas Supressoras de Tumor/genética , Adulto Jovem
10.
Epilepsia ; 53(4): 741-51, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22417003

RESUMO

PURPOSE: Intractability in epilepsy is difficult to define, and little is known about its onset, course, and duration. We investigated these aspects (as well as the occurrence of intractability) during long-term follow-up in patients with epilepsy, focusing on possible explanations for the variation in time of onset and duration of intractability. METHODS: After diagnosis, 453 patients with childhood-onset epilepsy had a 5-year follow-up with regular visits and data collection. Ten years later they received a questionnaire with items concerning epilepsy, which was completed by 413 patients resulting in a mean follow-up of 15 years. Intractability during the first 5 years was compared with that in the last year of follow-up. Intractability was defined as having no 3-month remission during a 1-year period despite adequate medical treatment. KEY FINDINGS: At least 12.1% of the cohort had a period of intractability during the 15-year follow-up, and 8.5% were intractable in the final year. Of the patients with idiopathic etiology 4.3% had a period of intractability versus 17.0% for those with cryptogenic, and 22.6% for those with remote symptomatic etiology (p < 0.001). Other risk factors at baseline were younger age at first seizure, generalized cryptogenic/symptomatic or localization-related symptomatic epilepsy, mental retardation, and febrile convulsions before enrollment. The cumulative risk of a period of intractability was 6.1% (95% confidence interval [CI] 3.7-8.5) at 2 years follow-up and 8.2% (95% CI 5.4-11.0) at 5 years. The mean time to onset of intractability during the first 5 years of follow-up was 1.6 (95% CI 1.3-2.0; median 1.0) years and the mean duration of intractability during these 5 years was 3.3 (95% CI 2.8-3.8; median 3.6) years. Fifteen patients were intractable only during the first 5 years of follow-up (group A), and 19 subjects were intractable both during the first 5 years and the last year of follow-up (group B). Compared with group A, group B had shorter remission and a longer time to intractability during the first 5 years and more were intractable in the fifth year of follow-up. Sixteen other patients had a late onset of intractability after 5 years of follow-up, sometimes after long periods of remission (group C). No significant differences in baseline characteristics were found among groups A, B, and C, but slightly more children in groups B and C became mentally retarded during the follow-up. In all groups, antiepileptic drugs were of little use in preventing and ending intractability. SIGNIFICANCE: There is a large unpredictable variation in time of onset, course, and duration of intractability, with a higher chance of final intractability after a poor course during the first 5 years of follow-up. The natural course of epilepsy probably best explains the variable course of intractability. The effect of medication seems to be minor.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologia , Adolescente , Análise de Variância , Criança , Pré-Escolar , Epilepsia/diagnóstico , Feminino , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Países Baixos/epidemiologia , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Falha de Tratamento
12.
Acta Physiol (Oxf) ; 235(1): e13800, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35156297

RESUMO

AIM: Loss-of-function KCNMA1 variants cause Liang-Wang syndrome (MIM #618729), a newly identified multiple malformation syndrome with a broad spectrum of developmental and neurological phenotypes. However, the full spectrum of clinical features and underlying pathogenic mechanisms need full elucidation. METHODS: Exome sequencing was used to identify pathogenic variants. Patch-clamp recordings were performed to access the effects of KCNMA1 variants on BK channels. Total and membrane protein expression levels of BK channels were characterized using Western blotting. RESULTS: We report identification and functional characterization of two new de novo loss-of-function KCNMA1 variants p.(A172T) and p.(A314T) with characteristics of Liang-Wang syndrome. Variant p.(A172T) is associated with developmental delay, cognitive impairment and ataxia. Mechanistically, p.(A172T) abolishes BK potassium current, inhibits Mg2+ -dependent gating, but shifts conductance-voltage (G-V) curves to more positive potentials when complexed with WT channels. Variant p.(A314T) is associated with developmental delay, intellectual disability, cognitive impairment, mild ataxia and generalized epilepsy; suppresses BK current amplitude; and shifts G-V curves to more positive potentials when expressed with WT channels. In addition, two new patients with previously reported gain-of-function variants p.(N536H) and p.(N995S) are found to show epilepsy and paroxysmal dyskinesia as reported previously, but also exhibit additional symptoms of cognitive impairment and dysmorphic features. Furthermore, variants p.(A314T) and p.(N536H) reduced total and membrane levels of BK proteins. CONCLUSION: Our findings identified two new loss-of-function mutations of KCNMA1 associated with Liang-Wang syndrome, expanded the spectrum of clinical features associated with gain-of-function KCNMA1 variants and emphasized the overlapping features shared by gain-of-function and loss-of-function mutations.


Assuntos
Epilepsia , Deficiência Intelectual , Ataxia/genética , Epilepsia/genética , Epilepsia/patologia , Humanos , Deficiência Intelectual/genética , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/genética , Canais de Potássio Ativados por Cálcio de Condutância Alta/genética , Fenótipo
13.
Epilepsia ; 52(12): 2192-202, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22004073

RESUMO

PURPOSE: Epilepsy may have far-reaching consequences for patients, other than having seizures and medication. At 15 years after diagnosis, this study investigates health perception, restrictions due to epilepsy, living arrangements (including marital status and offspring), and the educational and occupational attainment of patients with childhood-onset epilepsy. METHODS: A total of 453 patients with epilepsy had a 5-year follow-up since diagnosis with regular visits and data collection. Ten years later, a questionnaire addressing epilepsy was completed by 413 patients, resulting in a mean follow-up of 15 years. Subjects were compared with age peers of the Dutch population for each etiologic group separately, and also for subjects with/without a 5-year terminal remission regardless of treatment. Age-adjusted standardized incidence rates were calculated for each variable. KEY FINDINGS: Subjects with normal intelligence had a health perception comparable with that of the general population, but significantly more subjects without remission had a worse health perception, especially those still using medication. Restrictions and symptoms due to epilepsy were reported by 14% of the subjects, mainly by those without remission or with ongoing medication. The living arrangement of subjects with idiopathic or cryptogenic etiology was similar to that of Dutch persons of the same age (age peers). Subjects with remote symptomatic etiology less often lived independently or with a partner, and more frequently resided in an institution or living group for the disabled. Those with and without remission were more often part of another household, mainly due (in both groups) to having a remote symptomatic etiology. Rates of having a partner and offspring were significantly reduced only for subjects with remote symptomatic etiology. Fewer students with idiopathic/remote symptomatic etiology and students in remission followed higher vocational or scientific education. In these latter groups, the highest attained education of employees was lower than expected. The employment status of subjects with idiopathic or cryptogenic etiology was comparable with that of their Dutch age peers, but fewer subjects with remote symptomatic etiology were employed and more of them were part of the dependent population. However, for those in the labor force (employed/unemployed) all employment rates were ≥90%, even for those with remote symptomatic etiology. Nevertheless, fewer employees than expected had a higher vocational or scientific level of occupation, even those with idiopathic etiology and those in remission. SIGNIFICANCE: Health perception, living arrangement, and socioeconomic status were influenced by epilepsy, comorbidities, or treatment, particularly for subjects with remote symptomatic etiology or no remission. The group in remission fared less well than expected, mainly due to the numbers of subjects with remote symptomatic etiology in this group. In line with others, we conclude that childhood-onset epilepsy is associated with lower educational attainment, even for subjects with idiopathic etiology and subjects in remission; probably related to this, their occupational level was also lower than expected.


Assuntos
Epilepsia , Estado Civil , Percepção , Classe Social , Atividades Cotidianas , Adolescente , Adulto , Fatores Etários , Criança , Estudos de Coortes , Escolaridade , Emprego , Epilepsia/epidemiologia , Epilepsia/fisiopatologia , Epilepsia/psicologia , Feminino , Humanos , Masculino , Países Baixos/epidemiologia , Estudos Retrospectivos , Inquéritos e Questionários , Adulto Jovem
14.
Res Vet Sci ; 136: 209-219, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33689877

RESUMO

Stray cat population management is an important worldwide issue. Understanding citizen attitudes towards stray cat control options is vital to the success of controlling stray cat numbers, as public perception affects the acceptance of, support for and collaboration in stray cat management policies. Audience segmentation, as to enable each group to be engaged in the stray cat management policy, is important for the success of the interventions. Therefore a web-based survey was conducted among Flemish citizens in order to examine differences in acceptance towards seven management scenarios: household cat neutering with financial support for the owner, household cat neutering without financial support for the owner, encouraging responsible household cat ownership, trapping stray cats and taking them to a shelter, trapping and neutering stray cats for release into a managed "cat colony" (composed by so called "community cats"), trapping and killing of stray cats, and undertaking no action. A total of 4059 valid responses were collected and the proportions of agreement were compared across the different management scenarios using the two-sample z-test. Interactions among factors that influenced each management scenario were investigated using the CHAID (Chi-squared Automatic Interaction Detection) analysis and visualized on a tree. Our results showed that fostering responsible household cat ownership (89.9%) and conversion of stray cats to "community cats" (76.3%) were most supported by respondents in our sample (which consisted mainly of females, cat-lovers, and families without children). Least supported were the killing of stray cats (7.7%) and undertaking no action (3.3%). The demographic analyses revealed that for the acceptance of management scenarios there were three important factors (attitude towards cats, area of residence, and gender), two weaker factors (education and having children) and two which had almost no impact (age and cat ownership). We propose that future studies should focus on the effect of 'area of residence', 'having children' and 'education'. In conclusion, our research confirms that management of and communication on stray cat strategies should not be developed with a one-size-fits-all approach. Efforts should be tailored to each audience segment, thus adapted to the area of residence and human characteristics.


Assuntos
Opinião Pública , Animais , Animais Selvagens , Atitude , Bélgica/epidemiologia , Castração/veterinária , Gatos/cirurgia , Feminino , Humanos , Masculino , Propriedade , Controle da População , Inquéritos e Questionários
15.
Epilepsia ; 51(7): 1189-97, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20557350

RESUMO

PURPOSE: To study the course and outcome of childhood-onset epilepsy during 15-year follow-up (FU). METHODS: We extended FU in 413 of 494 children with new-onset epilepsy recruited in a previously described prospective hospital-based study by questionnaire. RESULTS: Mean FU was 14.8 years (range 11.6-17.5 years). Five-year terminal remission (TR) was reached by 71% of the cohort. Course during FU was favorable in 50%, improving in 29%, and poor or deteriorating in 16%. Mean duration of seizure activity was 6.0 years (range 0-21.5 years), strongly depending on etiology and epilepsy type. Duration was <1 year in 25% of the cohort and exceeded 12 years in another 25%. Antiepileptic drugs (AEDs) were used by 86% during a mean of 7.4 years: one-third had their last seizure within 1 year of treatment, and one-third continued treatment at the end, although some had a 5-year TR. At last contact, 9% of the cohort was intractable. In multivariate analysis, predictors were nonidiopathic etiology, febrile seizures, no 3-month remission, and early intractability. Eighteen patients died; 17 had remote symptomatic etiology. Standardized mortality ratio for remote symptomatic etiology was 31.6 [95% confidence interval (CI) 18.4-50.6], versus 0.8 [95% CI 0.02-4.2] for idiopathic/cryptogenic etiology. DISCUSSION: In most children with newly diagnosed epilepsy, the long-term prognosis of epilepsy is favorable, and in particular, patients with idiopathic etiology will eventually reach remission. In contrast, epilepsy remains active in approximately 30% and becomes intractable in approximately 10%. AEDs probably do not influence epilepsy course; they merely suppress seizures. Mortality is significantly higher only in those with remote symptomatic etiology.


Assuntos
Epilepsia/diagnóstico , Epilepsia/terapia , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Estudos de Coortes , Epilepsia/epidemiologia , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Países Baixos/epidemiologia , Resultado do Tratamento , Adulto Jovem
16.
Sleep ; 43(12)2020 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-32505131

RESUMO

STUDY OBJECTIVES: To ascertain the presence of cognitive and attention problems in treatment naïve children with narcolepsy type 1 (NT1) and to explore whether children recently diagnosed with NT1 improve with respect to cognition and attention problems 1 year after regular treatment for NT1. METHODS: A total of 15 treatment naïve children (7-15 years) with recently diagnosed NT1 were recruited from three sleep medicine centers in the Netherlands. The control group consisted of 15 healthy children, being frequency matched on age and gender. Both groups were investigated at baseline to examine intelligence profile (Wechsler Intelligence Scale for Children [WISC] III), attention problems, and processing speed (Bourdon Vos and sustained attention to respond task [SART]). These tests were repeated in children with NT1 1 year after regular (behavioral and medication) treatment for NT1. RESULTS: Children with NT1 scored significantly lower on the verbal scale and processing speed subscale of the WISC III, showed more fluctuations in reaction time of the Bourdon Vos and made more mistakes during the SART than the healthy control group at baseline. Children with NT1 significantly improved on total IQ score, and on the WISC indices processing speed, and perceptual organization 1 year after treatment. At follow-up, test scores of treated children were largely comparable to those of the control group at baseline. CONCLUSIONS: Children with NT1 show improvement in several cognitive domains 1 year after start of treatment. Our findings stress the need for early detection and treatment of narcolepsy in childhood.


Assuntos
Narcolepsia , Criança , Cognição , Humanos , Inteligência , Narcolepsia/tratamento farmacológico , Países Baixos
17.
Epilepsia ; 50(3): 415-21, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19054418

RESUMO

PURPOSE: To evaluate the feasibility and safety of intravenous (iv) levetiracetam (LEV) added to the standard therapeutic regimen in adults with status epilepticus (SE), and as secondary objective to assess a population pharmacokinetic (PK) model for ivLEV in patients with SE. METHODS: In 12 adults presenting with SE, 2,500 mg ivLEV was added as soon as possible to standardized protocol, consisting of iv clonazepam and/or rectal diazepam, as needed followed by phenytoin or valproic acid. ivLEV was administered over approximately 5 min, in general after administration of clonazepam, regardless the need for further treatment. During 24-h follow-up, patients were observed for any clinically relevant side-effects. Blood samples for PK analysis were available in 10 patients. A population PK model was developed by iterative two-stage Bayesian analysis and compared to PK data of healthy volunteers. RESULTS: Eleven patients with a median age of 60 years were included in the per protocol analysis. Five were diagnosed as generalized-convulsive SE, five as partial-convulsive SE, and one as a nonconvulsive SE. The median time from hospital admission to ivLEV was 36 min. No serious side effects could be related directly to the administration of ivLEV. During PK analysis, four patients showed a clear distribution phase, lacking in the others. The PK of the population was best described by a two-compartment population model. Mean (standard deviation, SD) population parameters included volume of distribution of central compartment: 0.45 (0.084) L/kg; total body clearance: 0.0476 (0.0147) L/h/kg; distribution rate constants, central to peripheral compartment (k(12)): 0.24 (0.12)/h, and peripheral to central (k(21)): 0.70 (0.22)/h. Mean maximal plasma concentration was 85 (19) mg/L. DISCUSSION: The addition of ivLEV to the standard regimen for controlling SE seems feasible and safe. PK data of ivLEV in patients with SE correspond to earlier values derived from healthy volunteers, confirming a two-compartment population model.


Assuntos
Anticonvulsivantes/administração & dosagem , Piracetam/análogos & derivados , Estado Epiléptico/tratamento farmacológico , Adulto , Idoso , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/farmacocinética , Teorema de Bayes , Disponibilidade Biológica , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Infusões Intravenosas , Levetiracetam , Masculino , Taxa de Depuração Metabólica/fisiologia , Pessoa de Meia-Idade , Piracetam/administração & dosagem , Piracetam/efeitos adversos , Piracetam/farmacocinética , Estudos Prospectivos , Estado Epiléptico/sangue
18.
Eur J Paediatr Neurol ; 23(5): 707-715, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31466810

RESUMO

OBJECTIVES: To compare physical activity (PA), fatigue and sleep quality in adolescents and young adults (AYAs) after mild TBI (mTBI) to persons of similar age after orthopedic injury (OI) on the longer term. SETTING: Follow-up at least 6 months after visiting the emergency department of one of 2 general hospitals. PARTICIPANTS: Forty-nine patients aged 12-25 years (mean 18.4 years), diagnosed with mTBI and 54 patients aged 12-25 years (mean 15.8 years) with OI. DESIGN: Cross-sectional electronic survey study. MAIN OUTCOME MEASURES: The Activity Questionnaire for Adults and Adolescents with results dichotomized for meeting/not meeting Dutch Health Enhancing PA recommendations (D-HEPA), the Checklist Individual Strength (range 20-140, low-high) measuring fatigue, and the Pittsburgh Sleep Quality Index (range 0-21, high-low) measuring sleep quality were administered. RESULTS: Patients with mTBI less frequently met D-HEPA recommendations than patients with OI (49% vs. 70%; OR 2.87, 95%CI 1.07, 7.72) and reported more concentration-related fatigue problems (mean 19.1 (SD 8.0), mean 13.9 (SD 7.8), respectively; ß 3.98, 95%CI 0.39, 7.56), after adjusting for potential confounders, sex, BMI, age and time since injury. No differences were found in sleep quality. CONCLUSIONS: Identifying symptoms and limitations in activities is important after mTBI so that rehabiliation treatment can be initiated. Whether physical activity or fatigue is the best target for treatment remains to be established.


Assuntos
Concussão Encefálica/complicações , Exercício Físico , Fadiga/etiologia , Sono , Adolescente , Adulto , Criança , Estudos Transversais , Fadiga/epidemiologia , Feminino , Humanos , Masculino , Inquéritos e Questionários , Adulto Jovem
19.
Sleep ; 42(2)2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30476304

RESUMO

Study Objectives: To explore impairments in social functioning in children with narcolepsy compared to healthy children. Methods: Parents of 53 pediatric patients with narcolepsy type 1 and 64 matched healthy children completed the Social Responsiveness Scale (SRS) and the Child Behavior Checklist 6-18 (CBCL 6-18). Results: Patients scored significantly higher on the total score of the SRS (median 56, interquartile range [IQR] 23.5) compared to controls (median 44.5, IQR 8.5, U = 797.0, p < 0.001). Patients also scored higher on the sum of the CBCL 6-18 subscales indicative of social functioning (Withdrawn/Depressed, Social Problems, and Thought Problems; median 183, IQR 30.5) compared to controls (median 155, IQR 13, U = 500.0, p < 0.001). A total of 24 patients (45.3%) reported at least mild-to-moderate difficulties in social functioning compared to seven controls (10.9%, χ2 = 17.165, p < 0.001). Eleven patients (20.8%) and only one control (1.6%) had T scores above 75, which points to severely impaired social functioning (χ2 = 11.602, p = 0.001). Within the patient group, girls reported mild-to-moderate difficulties in social functioning significantly more often compared to boys on the SRS (77.8% versus 28.6%, χ2 = 17.560, p < 0.001). Conclusions: Impaired social functioning is common in children with narcolepsy type 1, especially in girls. Questionnaires such as the SRS and the CBCL 6-18 may help in early detection of social problems in pediatric narcolepsy. Recognition of these problems could be valuable in the management of young people with narcolepsy.


Assuntos
Comportamento Infantil/psicologia , Relações Interpessoais , Narcolepsia/psicologia , Comportamento Problema/psicologia , Adolescente , Criança , Depressão , Feminino , Humanos , Masculino , Pais , Inquéritos e Questionários
20.
Epileptic Disord ; 21(2): 141-153, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31017575

RESUMO

It is unknown whether treatment with antiepileptic drugs in children with epilepsy with a presumed good prognosis is always necessary. We aimed to study the course of newly diagnosed epilepsy in children with a presumed good prognosis who are managed without AED treatment. A total of 151 children (one month to 12 years of age) with two to five lifetime unprovoked seizures (excluding febrile convulsions), were followed for three years. Treatment was initially withheld. Children with symptomatic epilepsy, or absence or myoclonic epilepsy, were excluded. AED treatment was started after >10 lifetime seizures or an episode of status epilepticus during follow-up, or if the parents or treating physician deemed it otherwise necessary. During follow-up, 113 children continued to meet our criteria for refraining from treatment with antiepileptic drugs, yet 30 started treatment at the request of the parents. Thirty-eight children at some time met the criteria to start treatment, but the parents of 16 declined treatment. In all, 99 (66%) children maintained the no-treatment regime. Ninety-eight children (65% of 151) reached terminal remission for at least one year, including 83 who did not receive antiepileptic drug treatment (84% of the untreated 99). Mean terminal remission was significantly longer in the group with a total of <10 seizures compared to those with >10 seizures. Treatment did not increase the length of terminal remission. Adverse events, including traumatic injury, occurred equally in the treated and untreated children. Measures of quality of life suggested a better outcome in those without treatment. Children with newly diagnosed epilepsy with a presumed good prognosis may not need immediate AED treatment. Postponing treatment does not alter the chance of remission or the risk of accidents and adverse events and appears to be associated with a good quality of life.


Assuntos
Anticonvulsivantes/administração & dosagem , Epilepsia/tratamento farmacológico , Criança , Pré-Escolar , Epilepsia/complicações , Epilepsia/diagnóstico , Epilepsia/fisiopatologia , Feminino , Humanos , Lactente , Masculino , Prognóstico , Estudos Prospectivos , Indução de Remissão , Remissão Espontânea
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