67 research outputs found

    Prenatal screening of sialic acid storage disease and confirmation in cultured fibroblasts by LC-MS/MS

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    Sialic acid storage disease (SASD) is an inborn error resulting from defects in the lysosomal membrane protein sialin. The SASD phenotypical spectrum ranges from a severe presentation, infantile sialic acid storage disease (ISSD) which may present as hydrops fetalis, to a relatively mild form, Salla disease. Screening for SASD is performed by determination of free sialic acid (FSA) in urine or amniotic fluid supernatant (AFS). Subsequent diagnosis of SASD is performed by quantification of FSA in cultured fibroblasts and by mutation analysis of the sialin gene, SLC17A5. We describe simple quantitative procedures to determine FSA as well as conjugated sialic acid in AFS, and FSA in cultured fibroblasts, using isotope dilution (13C3-sialic acid) and multiple reaction monitoring LC-ESI-MS/MS. The whole procedure can be performed in 2–4 h. Reference values in AFS were 0–8.2 μmol/L for 15–25 weeks of gestation and 3.2-12.0 μmol/L for 26–38 weeks of gestation. In AFS samples from five fetuses affected with ISSD FSA was 23.9-58.9 μmol/L demonstrating that this method is able to discriminate ISSD pregnancies from normal ones. The method was also validated for determination of FSA in fibroblast homogenates. FSA in SASD fibroblasts (ISSD; 20–154 nmol/mg protein, intermediate SASD; 12.9-15.1 nmol/mg, Salla disease; 5.9-7.4 nmol/mg) was clearly elevated compared to normal controls (0.3-2.2 nmol/mg). In conclusion, we report simple quantitative procedures to determine FSA in AFS and cultured fibroblasts improving both prenatal diagnostic efficacy for ISSD as well as confirmatory testing in cultured fibroblasts following initial screening in urine or AFS

    Mouse screen reveals multiple new genes underlying mouse and human hearing loss.

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    Adult-onset hearing loss is very common, but we know little about the underlying molecular pathogenesis impeding the development of therapies. We took a genetic approach to identify new molecules involved in hearing loss by screening a large cohort of newly generated mouse mutants using a sensitive electrophysiological test, the auditory brainstem response (ABR). We review here the findings from this screen. Thirty-eight unexpected genes associated with raised thresholds were detected from our unbiased sample of 1,211 genes tested, suggesting extreme genetic heterogeneity. A wide range of auditory pathophysiologies was found, and some mutant lines showed normal development followed by deterioration of responses, revealing new molecular pathways involved in progressive hearing loss. Several of the genes were associated with the range of hearing thresholds in the human population and one, SPNS2, was involved in childhood deafness. The new pathways required for maintenance of hearing discovered by this screen present new therapeutic opportunities

    Team creativity/innovation in culturally diverse teams: A meta‐analysis

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    This meta-analysis investigates the direction and strength of the relationship between diversity in culturally diverse teams and team creativity/innovation. We distinguish the effects of two diversity levels (i.e., surface- versus deep-level) in culturally diverse teams and examine the moderators suggested by the socio-technical systems framework (i.e., team virtuality and task characteristics in terms of task interdependence, complexity, and intellectiveness). Surface-level diversity in culturally diverse teams is not related to team creativity/innovation, while deep-level diversity in culturally diverse teams is positively related to team creativity/innovation. Moreover, surface-level diversity in culturally diverse teams and team creativity/innovation are negatively related for simple tasks, but unrelated for complex tasks. Deep-level diversity in culturally diverse teams and team creativity/innovation are positively related for collocated teams and interdependent tasks, but unrelated for non-collocated teams and independent tasks. We discuss the theoretical and practical implications

    Mouse screen reveals multiple new genes underlying mouse and human hearing loss

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    Adult-onset hearing loss is very common, but we know little about the underlying molecular pathogenesis impeding the development of therapies. We took a genetic approach to identify new molecules involved in hearing loss by screening a large cohort of newly generated mouse mutants using a sensitive electrophysiological test, the auditory brainstem response (ABR). We review here the findings from this screen. Thirty-eight unexpected genes associated with raised thresholds were detected from our unbiased sample of 1,211 genes tested, suggesting extreme genetic heterogeneity. A wide range of auditory pathophysiologies was found, and some mutant lines showed normal development followed by deterioration of responses, revealing new molecular pathways involved in progressive hearing loss. Several of the genes were associated with the range of hearing thresholds in the human population and one, SPNS2, was involved in childhood deafness. The new pathways required for maintenance of hearing discovered by this screen present new therapeutic opportunities

    Post universal health coverage trend and geographical inequalities of mortality in Thailand

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    BACKGROUND: Thailand has achieved remarkable improvement in health status since the achievement of universal health coverage in 2002. Health equity has improved significantly. However, challenges on health inequity still remain.This study aimed to determine the trends of geographical inequalities in disease specific mortality in Thailand after the country achieved universal health coverage. METHODS: National vital registration data from 2001 to 2014 were used to calculate age-adjusted mortality rate and standardized mortality ratio (SMR). To minimize large variations in mortality across administrative districts, the adjacent districts were systematically grouped into “super-districts” by taking into account the population size and proximity. Geographical mortality inequality among super-districts was measured by the coefficient of variation. Mixed effects modeling was used to test the difference in trends between super-districts. RESULTS: The overall SMR steadily declined from 1.2 in 2001 to 0.9 in 2014. The upper north and upper northeast regions had higher SMR whereas Greater Bangkok achieved the lowest SMR. Decreases in SMR were mostly seen in Greater Bangkok and the upper northern region. Coefficient of variation of SMR rapidly decreased from 20.0 in 2001 to 12.5 in 2007 and remained close to this value until 2014. The mixed effects modelling revealed significant differences in trends of SMR across super-districts. Inequality in mortality declined among adults (≥15 years old) but increased in children (0–14 years old). A declining trend in inequality of mortality was seen in almost all regions except Greater Bangkok where the inequality in SMR remained high throughout the study period. CONCLUSIONS: A decline in the adult mortality inequality across almost all regions of Thailand followed universal health coverage. Inequalities in child mortality rates and among residents of Greater Bangkok need further exploration

    Agronomic effectiveness of Phosphal-34 on flooded rice in acid soils

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    Therapy of Alkaptonuria

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