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Item does not contain fulltext, SPG8 is a rare autosomal dominant hereditary spastic paraplegia (AD-HSP), with only six SPG8 families described so far. Our purpose was to screen for KIAA0196 (SPG8) mutations in AD-HSP patients and to investigate their phenotype. Extensive family investigation was performed after positive KIAA0196 mutation analysis, which was part of an on-going mutation screening effort in AD-HSP patients. A novel pathogenic KIAA0196 mutation p.(Gly696Ala) was identified in two AD-HSP patients, who subsequently were shown to belong to a single large Dutch pedigree with more than 10 affected family members. The phenotype consisted of a pure HSP with ages at onset between 20 and 60 years, distally reduced vibration sense in the legs in all, and urinary urgency in seven out of 10 patients. Frequent features were exercise- or emotion-induced increase of spasticity and gait problems and chronic nonspecific lower back and joint pains. We have identified a fourth pathogenic KIAA0196 mutation in a Dutch HSP-family, the seventh family worldwide, with a less severe clinical course than described before.

Item does not contain fulltext, SPG8 is a rare autosomal dominant hereditary spastic paraplegia (AD-HSP), with only six SPG8 families described so far. Our purpose was to screen for KIAA0196 (SPG8) mutations in AD-HSP patients and to investigate their phenotype. Extensive family investigation was performed after positive KIAA0196 mutation analysis, which was part of an on-going mutation screening effort in AD-HSP patients. A novel pathogenic KIAA0196 mutation p.(Gly696Ala) was identified in two AD-HSP patients, who subsequently were shown to belong to a single large Dutch pedigree with more than 10 affected family members. The phenotype consisted of a pure HSP with ages at onset between 20 and 60 years, distally reduced vibration sense in the legs in all, and urinary urgency in seven out of 10 patients. Frequent features were exercise- or emotion-induced increase of spasticity and gait problems and chronic nonspecific lower back and joint pains. We have identified a fourth pathogenic KIAA0196 mutation in a Dutch HSP-family, the seventh family worldwide, with a less severe clinical course than described before.

Item does not contain fulltext, SPG8 is a rare autosomal dominant hereditary spastic paraplegia (AD-HSP), with only six SPG8 families described so far. Our purpose was to screen for KIAA0196 (SPG8) mutations in AD-HSP patients and to investigate their phenotype. Extensive family investigation was performed after positive KIAA0196 mutation analysis, which was part of an on-going mutation screening effort in AD-HSP patients. A novel pathogenic KIAA0196 mutation p.(Gly696Ala) was identified in two AD-HSP patients, who subsequently were shown to belong to a single large Dutch pedigree with more than 10 affected family members. The phenotype consisted of a pure HSP with ages at onset between 20 and 60 years, distally reduced vibration sense in the legs in all, and urinary urgency in seven out of 10 patients. Frequent features were exercise- or emotion-induced increase of spasticity and gait problems and chronic nonspecific lower back and joint pains. We have identified a fourth pathogenic KIAA0196 mutation in a Dutch HSP-family, the seventh family worldwide, with a less severe clinical course than described before.

Contains fulltext : 80569.pdf (publisher's version ) (Closed access), Lynch syndrome patients are susceptible to colorectal and endometrial cancers owing to inactivating germline mutations in mismatch repair genes, including MSH2 (ref. 1). Here we describe patients from Dutch and Chinese families with MSH2-deficient tumors carrying heterozygous germline deletions of the last exons of TACSTD1, a gene directly upstream of MSH2 encoding Ep-CAM. Due to these deletions, transcription of TACSTD1 extends into MSH2. The MSH2 promoter in cis with the deletion is methylated in Ep-CAM positive but not in Ep-CAM negative normal tissues, thus revealing a correlation between activity of the mutated TACSTD1 allele and epigenetic inactivation of the corresponding MSH2 allele. Gene silencing by transcriptional read-through of a neighboring gene in either sense, as demonstrated here, or antisense direction, could represent a general mutational mechanism. Depending on the expression pattern of the neighboring gene that lacks its normal polyadenylation signal, this may cause either generalized or mosaic patterns of epigenetic inactivation.

Contains fulltext : 80569.pdf (publisher's version ) (Closed access), Lynch syndrome patients are susceptible to colorectal and endometrial cancers owing to inactivating germline mutations in mismatch repair genes, including MSH2 (ref. 1). Here we describe patients from Dutch and Chinese families with MSH2-deficient tumors carrying heterozygous germline deletions of the last exons of TACSTD1, a gene directly upstream of MSH2 encoding Ep-CAM. Due to these deletions, transcription of TACSTD1 extends into MSH2. The MSH2 promoter in cis with the deletion is methylated in Ep-CAM positive but not in Ep-CAM negative normal tissues, thus revealing a correlation between activity of the mutated TACSTD1 allele and epigenetic inactivation of the corresponding MSH2 allele. Gene silencing by transcriptional read-through of a neighboring gene in either sense, as demonstrated here, or antisense direction, could represent a general mutational mechanism. Depending on the expression pattern of the neighboring gene that lacks its normal polyadenylation signal, this may cause either generalized or mosaic patterns of epigenetic inactivation.

Contains fulltext : 52007.pdf (publisher's version ) (Closed access), PURPOSE: To investigate the prevalence of unmet demands concerning autonomy and participation and to identify risk factors related to these unmet demands in patients with chronic stroke. METHOD: A cross-sectional study of 147 patients three years after stroke. We assessed perceived unmet care demands in relation to problems of participation and autonomy measured by the Impact on Participation and Autonomy Questionnaire (IPAQ). Socio-demographic and health characteristics were analysed as potential risk factors for the prevalence of unmet demands, using multivariate regression analysis. RESULTS: A total of 33% of the patients perceived at least one unmet demand in one of the IPAQ subdomains. Risk factors significantly related to the presence of unmet demands were younger age, motor impairment, fatigue and depressive symptoms. Findings indicate that the model including these factors was fairly accurate in identifying patients having unmet demands and those not having unmet demands. CONCLUSIONS: Unmet care demands were present in a substantial proportion of the stroke patients. The risk factors identified are helpful for clinicians and health care providers to recognize patients who are at risk of perceiving unmet care demands and to optimize care to patients with chronic stroke.

Contains fulltext : 52007.pdf (publisher's version ) (Closed access), PURPOSE: To investigate the prevalence of unmet demands concerning autonomy and participation and to identify risk factors related to these unmet demands in patients with chronic stroke. METHOD: A cross-sectional study of 147 patients three years after stroke. We assessed perceived unmet care demands in relation to problems of participation and autonomy measured by the Impact on Participation and Autonomy Questionnaire (IPAQ). Socio-demographic and health characteristics were analysed as potential risk factors for the prevalence of unmet demands, using multivariate regression analysis. RESULTS: A total of 33% of the patients perceived at least one unmet demand in one of the IPAQ subdomains. Risk factors significantly related to the presence of unmet demands were younger age, motor impairment, fatigue and depressive symptoms. Findings indicate that the model including these factors was fairly accurate in identifying patients having unmet demands and those not having unmet demands. CONCLUSIONS: Unmet care demands were present in a substantial proportion of the stroke patients. The risk factors identified are helpful for clinicians and health care providers to recognize patients who are at risk of perceiving unmet care demands and to optimize care to patients with chronic stroke.

Results of sediment transport calculations are often necessary in solving practical coastal engineering problems. (Sediment transport due to waves and currents). Many transport formulae have been proposed in literature in the past. Selection of the proper one while solving a particular problem, is a difficult task for a coastal engineer. In considering sediment transport under wave-current conditions it is worthwhile to make a distinction between two situations, viz.: The fluctuations in the orbital motion have to be fully taken into account in order to find the resulting sediment transport (intra-wave type of description; often: cross-shore sediment transport); - It is sufficient to take time-averaged effects of the waves into account in order to find the resulting sediment transport rate (intra-wave type of description is not required; often: longshore sediment transport). For the longshore sediment transport mode, transport formulae based on time-averaged velocity distributions and time-averaged sediment concentration distributions over the water depth can often be used. The present paper is restricted to this type of formula., Civil Engineering and Geosciences

Results of sediment transport calculations are often necessary in solving practical coastal engineering problems. (Sediment transport due to waves and currents). Many transport formulae have been proposed in literature in the past. Selection of the proper one while solving a particular problem, is a difficult task for a coastal engineer. In considering sediment transport under wave-current conditions it is worthwhile to make a distinction between two situations, viz.: The fluctuations in the orbital motion have to be fully taken into account in order to find the resulting sediment transport (intra-wave type of description; often: cross-shore sediment transport); - It is sufficient to take time-averaged effects of the waves into account in order to find the resulting sediment transport rate (intra-wave type of description is not required; often: longshore sediment transport). For the longshore sediment transport mode, transport formulae based on time-averaged velocity distributions and time-averaged sediment concentration distributions over the water depth can often be used. The present paper is restricted to this type of formula., Civil Engineering and Geosciences