Marginal folate inadequacy observed in a group of young children in Kwangju, Korea

Folate is important for multiple metabolic processes such as nucleic acid synthesis and interconversions, and cell division. Folate deficiency may be a risk factor for several pathologies, such as neural tube birth defects, dementia, and cardiovascular diseases. The objectives of this study were to estimate folate intakes and plasma concentrations of young children living in Kwangju, Korea. Three consecutive 24-h food recalls and fasting blood samples were obtained from 24 boys and 30 girls, aged 2-6 y, living in Kwangju, Korea. The daily folate intake (mean ± SD) of the children was 146.7 ± 73.6 µg dietary folate equivalents. No differences in folate intakes were observed by gender (p≥0.05). The mean folate intakes of the 2 and 3 y old groups were significantly lower (p<0.05) than those of 5 and 6 y old groups. Over half of subjects consumed <Korean Estimated Average Requirements for folate. The plasma folate concentration (mean ± SD) of all subjects was 19.2 ± 8.7 nmol/L, and there was no significant difference by age nor gender (p≥0.05). No significant correlation was observed between folate intakes and plasma folate concentrations. One subject (1.9%) in this study had a plasma folate concentration <6.8 nmol/L, which is indicative of folate deficiency. Approximately 24% of subjects had plasma folate concentrations of 6.8-13.4 nmol/L, which is representative of marginal folate status. In conclusion, some young children may have less than adequate folate status in Korea

Typical investigational medicinal products follow relatively uniform regulations in 10 European Clinical Research Infrastructures Network (ECRIN) countries

<p>Abstract</p> <p>Background</p> <p>In order to facilitate multinational clinical research, regulatory requirements need to become international and harmonised. The EU introduced the Directive 2001/20/EC in 2004, regulating investigational medicinal products in Europe.</p> <p>Methods</p> <p>We conducted a survey in order to identify the national regulatory requirements for major categories of clinical research in ten European Clinical Research Infrastructures Network (ECRIN) countries-Austria, Denmark, France, Germany, Hungary, Ireland, Italy, Spain, Sweden, and United Kingdom-covering approximately 70% of the EU population. Here we describe the results for regulatory requirements for typical investigational medicinal products, in the ten countries.</p> <p>Results</p> <p>Our results show that the ten countries have fairly harmonised definitions of typical investigational medicinal products. Clinical trials assessing typical investigational medicinal products require authorisation from a national competent authority in each of the countries surveyed. The opinion of the competent authorities is communicated to the trial sponsor within the same timelines, i.e., no more than 60 days, in all ten countries. The authority to which the application has to be sent to in the different countries is not fully harmonised.</p> <p>Conclusion</p> <p>The Directive 2001/20/EC defined the term 'investigational medicinal product' and all regulatory requirements described therein are applicable to investigational medicinal products. Our survey showed, however, that those requirements had been adopted in ten European countries, not for investigational medicinal products overall, but rather a narrower category which we term 'typical' investigational medicinal products. The result is partial EU harmonisation of requirements and a relatively navigable landscape for the sponsor regarding typical investigational medicinal products.</p

Health-related quality-of-life measures for long-term follow-up in children after major trauma

Objective: Our objective was to review measures of health-related quality of life (HRQL) for long-term follow up in children after major trauma and to determine the measures that are suitable for a large age range, reliable and valid, and cover a substantial amount of the domains of functioning using the International Classification of Functioning, Disability, and Health (ICF) of the World Health Organization (WHO). Methods: The Medline and EMBASE databases were searched in all years up to October 2007 for generic HRQL measures suitable for children aged 5-18 years old and validated in English or Dutch. Measures were reviewed with respect to the age range for which the measure was suitable and reliability, validity, and content related to the ICF. Results: The search resulted in 1,235 hits and 21 related articles. Seventy-nine papers met the inclusion criteria, describing in total 14 measures: Child Health and Illness Profile Adolescent and Child Edition (CHIP-AE/CE), Child Health Questionnaire Child and Parent Forms (CHQCF87/PF50/PF28), DISABKIDS, Functional Status II (FS II)(R), Health Utilities Index Mark 2 (HUI 2), KIDSCREEN 52/27, KINDL, Pediatric Quality of Life Inventory (PedsQL), TNO Institute of Prevention and Health and the Leiden University Hospital (TNO-AZL), TNO-AZL Children’s Quality Of Life (TACQOL), and Youth Quality of Life Instrument-Research Version (YQOL-R). Measures that were suitable for a large age range were CHQ-PF50/PF28, DISABKIDS, FS II(R), HUI 2, KIDSCREEN, PedsQL, and TACQOL. All measures had moderate to good psychometric properties, except for CHQ-PF50/PF28, KINDL, and TACQOL, which had either low internal consistency or bad test-retest reliability. The measures that covered more than six chapters of the ICF domains were CHIP-AE/CE, CHQ-CF87/PF50, DISABKIDS, KIDSCREEN-52, PedsQL, and TACQOL. Conclusions: DISABKIDS, KIDSCREEN 52, and Peds-QL are suitable for long-term follow-up measurement of HRQL in children after major trauma. They cover a large age range, have good psychometric properties, and cover the ICF substantially

A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling

J. Kaprio, A. Palotie, A. Raevuori-Helkamaa ja S. Ripatti ovat työryhmän Eating Disorders Working Group of the Psychiatric Genomics Consortium jäseniä. Erratum in: Sci Rep. 2017 Aug 21;7(1):8379, doi: 10.1038/s41598-017-06409-3We conducted a genome-wide association study (GWAS) of anorexia nervosa (AN) using a stringently defined phenotype. Analysis of phenotypic variability led to the identification of a specific genetic risk factor that approached genome-wide significance (rs929626 in EBF1 (Early B-Cell Factor 1); P = 2.04 x 10(-7); OR = 0.7; 95% confidence interval (CI) = 0.61-0.8) with independent replication (P = 0.04), suggesting a variant-mediated dysregulation of leptin signaling may play a role in AN. Multiple SNPs in LD with the variant support the nominal association. This demonstrates that although the clinical and etiologic heterogeneity of AN is universally recognized, further careful sub-typing of cases may provide more precise genomic signals. In this study, through a refinement of the phenotype spectrum of AN, we present a replicable GWAS signal that is nominally associated with AN, highlighting a potentially important candidate locus for further investigation.Peer reviewe

Clinical and molecular characterization of adult patients with late‐onset MTHFR deficiency

5,10‐Methylenetetrahydrofolate reductase (MTHFR) deficiency usually presents as a severe neonatal disease. This study aimed to characterize natural history, biological and molecular data, and response to treatment of patients with late‐onset MTHFR deficiency. The patients were identified through the European Network and Registry for Homocystinuria and Methylation Defects and the Adult group of the French Society for Inherited Metabolic Diseases; data were retrospectively colleted. To identify juvenile to adult‐onset forms of the disease, we included patients with a diagnosis established after the age of 10 years. We included 14 patients (median age at diagnosis: 32 years; range: 11‐54). At onset (median age: 20 years; range 9‐38), they presented with walking difficulties (n = 8), cognitive decline (n = 3) and/or seizures (n = 3), sometimes associated with mild mental retardation (n = 6). During the disease course, symptoms were almost exclusively neurological with cognitive dysfunction (93%), gait disorders (86%), epilepsy (71%), psychiatric symptoms (57%), polyneuropathy (43%), and visual deficit (43%). Mean diagnostic delay was 14 years. Vascular events were observed in 28% and obesity in 36% of the patients. One patient remained asymptomatic at the age of 55 years. Upon treatment, median total homocysteine decreased (from 183 μmol/L, range 69‐266, to 90 μmol/L, range 20‐142) and symptoms improved (n = 9) or stabilized (n = 4). Missense pathogenic variants in the C‐terminal regulatory domain of the protein were over‐represented compared to early‐onset cases. Residual MTHFR enzymatic activity in skin fibroblasts (n = 4) was rather high (17%‐58%). This series of patients with late‐onset MTHFR deficiency underlines the still unmet need of a prompt diagnosis of this treatable disease