4 research outputs found
Dynamic location problems with limited look-ahead
Background Among the most frequently encountered mutations in dilated cardiomyopathy (DCM) are those in the lamin A/C (LMNA) gene. Our goal was to analyze the LMNA gene in patients with DCM and/or conduction disease referred to the cardiogenetics outpatient clinic and to evaluate the prevalence of LMNA mutations and their clinical expression. Methods and Results The LMNA gene was screened in 61 index patients. Eleven mutations (including 6 novel) were identified, mainly in the subgroup of familial DCM with cardiac conduction disease (3/10 index patients) and in patients with DCM and Emery-Dreifuss, Limb-Girdle, or unclassified forms of muscular dystrophy (7/8 index patients). In addition, a mutation was identified in 1 of 4 families with only cardiac conduction disease. We did not identify any large deletions or duplications.Genotype-phenotype relationships revealed a high rate of sudden death and cardiac transplants in carriers of the p.N 195K mutation. Our study confirmed that the p.R225X mutation leads to cardiac conduction disease with late or no development of DCM, underscoring the importance of this mutation in putative familial "lone conduction disease." Nearly one third of LMNA mutation carriers had experienced a thromboembolic event. Conclusions This study highlights the role of LMNA mutations in DCM and related disorders. A severe phenotype in p.N 195K mutation carriers and preferential cardiac conduction disease in p.R225X carriers was encountered. Because of the clinical variability, including the development of associated symptoms in time, LMNA screening should be considered in patients with DCM or familial lone conduction diseas
Daphnid Life Cycle Responses to New Generation Flame Retardants
Relatively
hazardous brominated flame retardants (BFRs) are currently
substituted with halogen-free flame retardants (HFFRs). Consequently,
information on their persistence, bioaccumulation and toxicity (PBT)
is urgently needed. Therefore, we investigated the chronic toxicity
to the water flea <i>Daphnia magna</i> of two HFFRs, aluminum
diethylphosphinate (ALPI) and 9,10-dihyro-9-oxa-10-phosphaphenanthrene-oxide
(DOPO). The toxicity of ALPI increased from a 48 h LC<sub>50</sub> of 18 mg L<sup>–1</sup> to a 21 day LC<sub>50</sub> value
of 3.2 mg L<sup>–1</sup>, resulting in an acute-to-chronic
ratio of 5.6. This may imply a change in classification from low to
moderate toxicity. ALPI also affected sublethal life cycle parameters,
with an EC<sub>50</sub> of 2.8 mg L<sup>–1</sup> for cumulative
reproductive output and of 3.4 mg L<sup>–1</sup> for population
growth rate, revealing a nonspecific mode of action. DOPO showed only
sublethal effects with an EC<sub>50</sub> value of 48 mg L<sup>–1</sup> for cumulative reproductive output and an EC<sub>50</sub> value
of 73 mg L<sup>–1</sup> for population growth rate. The toxicity
of DOPO to <i>D. magna</i> was classified as low and likely
occurred above environmentally relevant concentrations, but we identified
specific effects on reproduction. Given the low chronic toxicity of
DOPO and the moderate toxicity of ALPI, based on this study only,
DOPO seems to be more suitable than ALPI for BFR replacement in polymers
Daphnid Life Cycle Responses to New Generation Flame Retardants
Relatively hazardous brominated flame retardants (BFRs) are currently substituted with halogen-free flame retardants (HFFRs). Consequently, information on their persistence, bioaccumulation and toxicity (PBT) is urgently needed. Therefore, we investigated the chronic toxicity to the water flea Daphnia magna of two HFFRs, aluminum diethylphosphinate (ALPI) and 9,10-dihyro-9-oxa-10-phosphaphenanthrene-oxide (DOPO). The toxicity of ALPI increased from a 48 h LC50 of 18 mg L-1 to a 21 day LC50 value of 3.2 mg L-1, resulting in an acute-to-chronic ratio of 5.6. This may imply a change in classification from low to moderate toxicity. ALPI also affected sublethal life cycle parameters, with an EC50 of 2.8 mg L-1 for cumulative reproductive output and of 3.4 mg L-1 for population growth rate, revealing a nonspecific mode of action. DOPO showed only sublethal effects with an EC50 value of 48 mg L-1 for cumulative reproductive output and an EC50 value of 73 mg L-1 for population growth rate. The toxicity of DOPO to D. magna was classified as low and likely occurred above environmentally relevant concentrations, but we identified specific effects on reproduction. Given the low chronic toxicity of DOPO and the moderate toxicity of ALPI, based on this study only, DOPO seems to be more suitable than ALPI for BFR replacement in polymers