RESUMO
BACKGROUND: Dysphagia is common in Huntington's disease (HD) affecting all phases of swallowing. Correlations exist between non-instrumental measures of dysphagia and clinical features of HD, including age, disease duration and degree of motor impairment. Lack of instrumental data limits our ability to wholly characterize HD-related dysphagia and prognosticate swallowing changes over time. OBJECTIVE: To retrospectively describe a relatively large database of videofluoroscopic studies (VFSSs) and determine the relationships between dysphagia and HD clinical parameters, including disease duration and burden of pathology score. METHODS: Medical and swallowing data of 49 individuals with HD and dysphagia were examined. VFSS data were interpreted using the Bethlehem Assessment Scale and Penetration-Aspiration Scale. Data from clinical bedside examination and social information were collated to describe the impact of dysphagia in HD. Repeated VFSS data were available for seven individuals. RESULTS: Swallowing was characterized by lingual dysfunction, reduced soft palate elevation, delayed pharyngeal swallow initiation, and inability to clear matter from the pharynx. Two-thirds of cases presented with compromised airway protection with both liquid and solid consistencies. Tachyphagia and difficulty self-feeding were common. Dysphagia correlated with disease severity and duration. Longitudinal analysis revealed a mixed pattern of progression with some individuals presenting with worsening dysphagia whilst others appeared to remain stable or improved in function. CONCLUSIONS: Dysphagia in HD is exacerbated by difficulties with self-feeding and monitoring feeding rate. Burden of pathology relates to pharyngeal swallow initiation and penetration and aspiration of fluid. Dysphagia did not appear to worsen in a systematic way in a subset of participants.
Assuntos
Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/fisiopatologia , Progressão da Doença , Doença de Huntington/diagnóstico , Doença de Huntington/fisiopatologia , Adulto , Transtornos de Deglutição/etiologia , Feminino , Fluoroscopia , Humanos , Doença de Huntington/complicações , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
After the senior author took chairmanship in Helsinki University Hospital in, he led the department into making neurosurgical operations much faster, safer and workflow more efficient, and at the same time maintaining high surgical quality and results. The aim was to describe the philosophies and style of Helsinki Microneurosurgery. The philosophies of Helsinki Neurosurgery are categorized into two concepts: The operation room TEAM concept and the main principle "Simple, clean, fast and respecting the normal anatomy". The way to be efficient is to find good methods based on logic, reason and experience. Specific and systematic procedures before the microneurosurgery followed by high quality skills under the microscope are of utmost importance. Moreover, intraoperatively, neuroanesthesia has to provide good surgical conditions. Today, Helsinki University Central hospital Department of Neurosurgery has an annual workflow 3500 neurosurgical operations. We believe that microneurosurgical treatment remains to be important for years ahead, and neurosurgeons of great hearts, minds and skills are welcomed all over the world.
Assuntos
Microcirurgia/métodos , Microcirurgia/normas , Procedimentos Neurocirúrgicos/métodos , Procedimentos Neurocirúrgicos/normas , HumanosRESUMO
Xylans constitute the main non-cellulosic polysaccharide in the secondary cell walls of plants. Several genes predicted to encode glycosyltransferases are required for the synthesis of the xylan backbone even though it is a homopolymer consisting entirely of ß-1,4-linked xylose residues. The putative glycosyltransferases IRX9, IRX14, and IRX10 (or the paralogs IRX9L, IRX14L, and IRX10L) are required for xylan backbone synthesis in Arabidopsis. To investigate the function of IRX9, IRX9L, and IRX14, we identified amino acid residues known to be essential for catalytic function in homologous mammalian proteins and generated modified cDNA clones encoding proteins where these residues would be mutated. The mutated gene constructs were used to transform wild-type Arabidopsis plants and the irx9 and irx14 mutants, which are deficient in xylan synthesis. The ability of the mutated proteins to complement the mutants was investigated by measuring growth, determining cell wall composition, and microscopic analysis of stem cross-sections of the transgenic plants. The six different mutated versions of IRX9 and IRX9-L were all able to complement the irx9 mutant phenotype, indicating that residues known to be essential for glycosyltransferases function in homologous proteins are not essential for the biological function of IRX9/IRX9L. Two out of three mutated IRX14 complemented the irx14 mutant, including a mutant in the predicted catalytic amino acid. A IRX14 protein mutated in the substrate-binding DxD motif did not complement the irx14 mutant. Thus, substrate binding is important for IRX14 function but catalytic activity may not be essential for the function of the protein. The data indicate that IRX9/IRX9L have an essential structural function, most likely by interacting with the IRX10/IRX10L proteins, but do not have an essential catalytic function. Most likely IRX14 also has primarily a structural role, but it cannot be excluded that the protein has an important enzymatic activity.
Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Glicosiltransferases/metabolismo , Pentosiltransferases/metabolismo , Xilanos/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Glicosiltransferases/genética , Mutagênese Sítio-Dirigida , Mutação , Pentosiltransferases/genética , Filogenia , Xilanos/genéticaRESUMO
BACKGROUND: Cost-efficient generation of second-generation biofuels requires plant biomass that can easily be degraded into sugars and further fermented into fuels. However, lignocellulosic biomass is inherently recalcitrant toward deconstruction technologies due to the abundant lignin and cross-linked hemicelluloses. Furthermore, lignocellulosic biomass has a high content of pentoses, which are more difficult to ferment into fuels than hexoses. Engineered plants with decreased amounts of xylan in their secondary walls have the potential to render plant biomass a more desirable feedstock for biofuel production. RESULTS: Xylan is the major non-cellulosic polysaccharide in secondary cell walls, and the xylan deficient irregular xylem (irx) mutants irx7, irx8 and irx9 exhibit severe dwarf growth phenotypes. The main reason for the growth phenotype appears to be xylem vessel collapse and the resulting impaired transport of water and nutrients. We developed a xylan-engineering approach to reintroduce xylan biosynthesis specifically into the xylem vessels in the Arabidopsis irx7, irx8 and irx9 mutant backgrounds by driving the expression of the respective glycosyltransferases with the vessel-specific promoters of the VND6 and VND7 transcription factor genes. The growth phenotype, stem breaking strength, and irx morphology was recovered to varying degrees. Some of the plants even exhibited increased stem strength compared to the wild type. We obtained Arabidopsis plants with up to 23% reduction in xylose levels and 18% reduction in lignin content compared to wild-type plants, while exhibiting wild-type growth patterns and morphology, as well as normal xylem vessels. These plants showed a 42% increase in saccharification yield after hot water pretreatment. The VND7 promoter yielded a more complete complementation of the irx phenotype than the VND6 promoter. CONCLUSIONS: Spatial and temporal deposition of xylan in the secondary cell wall of Arabidopsis can be manipulated by using the promoter regions of vessel-specific genes to express xylan biosynthetic genes. The expression of xylan specifically in the xylem vessels is sufficient to complement the irx phenotype of xylan deficient mutants, while maintaining low overall amounts of xylan and lignin in the cell wall. This engineering approach has the potential to yield bioenergy crop plants that are more easily deconstructed and fermented into biofuels.