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1.
Genome Med ; 11(1): 12, 2019 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-30819258

RESUMO

BACKGROUND: Neurodevelopmental disorders are genetically and phenotypically heterogeneous encompassing developmental delay (DD), intellectual disability (ID), autism spectrum disorders (ASDs), structural brain abnormalities, and neurological manifestations with variants in a large number of genes (hundreds) associated. To date, a few de novo mutations potentially disrupting TCF20 function in patients with ID, ASD, and hypotonia have been reported. TCF20 encodes a transcriptional co-regulator structurally related to RAI1, the dosage-sensitive gene responsible for Smith-Magenis syndrome (deletion/haploinsufficiency) and Potocki-Lupski syndrome (duplication/triplosensitivity). METHODS: Genome-wide analyses by exome sequencing (ES) and chromosomal microarray analysis (CMA) identified individuals with heterozygous, likely damaging, loss-of-function alleles in TCF20. We implemented further molecular and clinical analyses to determine the inheritance of the pathogenic variant alleles and studied the spectrum of phenotypes. RESULTS: We report 25 unique inactivating single nucleotide variants/indels (1 missense, 1 canonical splice-site variant, 18 frameshift, and 5 nonsense) and 4 deletions of TCF20. The pathogenic variants were detected in 32 patients and 4 affected parents from 31 unrelated families. Among cases with available parental samples, the variants were de novo in 20 instances and inherited from 4 symptomatic parents in 5, including in one set of monozygotic twins. Two pathogenic loss-of-function variants were recurrent in unrelated families. Patients presented with a phenotype characterized by developmental delay, intellectual disability, hypotonia, variable dysmorphic features, movement disorders, and sleep disturbances. CONCLUSIONS: TCF20 pathogenic variants are associated with a novel syndrome manifesting clinical characteristics similar to those observed in Smith-Magenis syndrome. Together with previously described cases, the clinical entity of TCF20-associated neurodevelopmental disorders (TAND) emerges from a genotype-driven perspective.


Assuntos
Anormalidades Craniofaciais/genética , Deficiências do Desenvolvimento/genética , Mutação INDEL , Deficiência Intelectual/genética , Hipotonia Muscular/genética , Síndrome de Smith-Magenis/genética , Fatores de Transcrição/genética , Adolescente , Criança , Pré-Escolar , Anormalidades Craniofaciais/patologia , Deficiências do Desenvolvimento/patologia , Feminino , Humanos , Lactente , Deficiência Intelectual/patologia , Masculino , Hipotonia Muscular/patologia , Síndrome de Smith-Magenis/patologia , Fatores de Transcrição/metabolismo , Adulto Jovem
3.
Am J Hum Genet ; 104(2): 319-330, 2019 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-30639322

RESUMO

ZMIZ1 is a coactivator of several transcription factors, including p53, the androgen receptor, and NOTCH1. Here, we report 19 subjects with intellectual disability and developmental delay carrying variants in ZMIZ1. The associated features include growth failure, feeding difficulties, microcephaly, facial dysmorphism, and various other congenital malformations. Of these 19, 14 unrelated subjects carried de novo heterozygous single-nucleotide variants (SNVs) or single-base insertions/deletions, 3 siblings harbored a heterozygous single-base insertion, and 2 subjects had a balanced translocation disrupting ZMIZ1 or involving a regulatory region of ZMIZ1. In total, we identified 13 point mutations that affect key protein regions, including a SUMO acceptor site, a central disordered alanine-rich motif, a proline-rich domain, and a transactivation domain. All identified variants were absent from all available exome and genome databases. In vitro, ZMIZ1 showed impaired coactivation of the androgen receptor. In vivo, overexpression of ZMIZ1 mutant alleles in developing mouse brains using in utero electroporation resulted in abnormal pyramidal neuron morphology, polarization, and positioning, underscoring the importance of ZMIZ1 in neural development and supporting mutations in ZMIZ1 as the cause of a rare neurodevelopmental syndrome.

5.
Am J Hum Genet ; 103(2): 305-316, 2018 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-30057029

RESUMO

Next-generation sequencing combined with international data sharing has enormously facilitated identification of new disease-associated genes and mutations. This is particularly true for genetically extremely heterogeneous entities such as neurodevelopmental disorders (NDDs). Through exome sequencing and world-wide collaborations, we identified and assembled 20 individuals with de novo variants in FBXO11. They present with mild to severe developmental delay associated with a range of features including short (4/20) or tall (2/20) stature, obesity (5/20), microcephaly (4/19) or macrocephaly (2/19), behavioral problems (17/20), seizures (5/20), cleft lip or palate or bifid uvula (3/20), and minor skeletal anomalies. FBXO11 encodes a member of the F-Box protein family, constituting a subunit of an E3-ubiquitin ligase complex. This complex is involved in ubiquitination and proteasomal degradation and thus in controlling critical biological processes by regulating protein turnover. The identified de novo aberrations comprise two large deletions, ten likely gene disrupting variants, and eight missense variants distributed throughout FBXO11. Structural modeling for missense variants located in the CASH or the Zinc-finger UBR domains suggests destabilization of the protein. This, in combination with the observed spectrum and localization of identified variants and the lack of apparent genotype-phenotype correlations, is compatible with loss of function or haploinsufficiency as an underlying mechanism. We implicate de novo missense and likely gene disrupting variants in FBXO11 in a neurodevelopmental disorder with variable intellectual disability and various other features.

6.
Am J Med Genet A ; 176(2): 319-329, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29194955

RESUMO

The direct transmission of microscopically visible unbalanced chromosome abnormalities (UBCAs) is rare and usually has phenotypic consequences. Here we report four families in which a normal phenotype was initially found in one or more family members. Each UBCA was interpreted with regard to overlapping examples and factors previously associated with transmitted imbalances including incidental ascertainment, low gene density, benign copy number variation (CNV) content, and gene relatedness. A 4.56 Mb deletion of 8p23.1-p23.2 was thought to be causal in the affected proband but showed incomplete penetrance in her mother and sibling (Family 1). Incomplete penetrance was also associated with a 10.88 Mb duplication of 13q21.31-q22.1 (Family 3) and dosage insensitivity with a 17.6 Mb deletion of 22pter-q11.21 (Family 4) that were both ascertained at prenatal diagnosis and each found in 4 unaffected family members. The 22pter-q11.21 deletion is part of a region with high benign CNV content and supports the mapping of cat eye syndrome to a 600 kb interval of 22q11.1-q11.21. Low gene densities of less than 2.0 genes/Mb were found in each of these three families but only after segmentally duplicated genes were excluded from the deletions of 8p and 22q. In contrast, gene density was average and variable expressivity associated with a 3.59 Mb duplication of 8p23.1 incidentally ascertained for paternal infertility (Family 2). Our results indicate that a greater degree of direct parental transmission, incomplete penetrance, and variable expression are features of both sub-microscopic CNVs and UBCAs with relatively low gene and high benign CNV content.

7.
Magn Reson Med ; 77(3): 970-978, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27062518

RESUMO

PURPOSE: To demonstrate a new MR imaging approach that unambiguously identifies and quantitates contrast agents based on intrinsic agent properties such as r1 , r2 , r2*, and magnetic susceptibility. The approach is referred to as magnetic barcode imaging (MBI). METHODS: Targeted and bioresponsive contrast agents were imaged in agarose phantoms to generate T1 , T2 , T2*, and quantitative susceptibility maps. The parameter maps were processed by a machine learning algorithm that is trained to recognize the contrast agents based on these parameters. The output is a quantitative map of contrast agent concentration, identity, and functional state. RESULTS: MBI allowed the quantitative interpretation of intensities, removed confounding backgrounds, enabled contrast agent multiplexing, and unambiguously detected the activation and binding states of bioresponsive and targeted contrast agents. CONCLUSION: MBI has the potential to overcome significant limitations in the interpretation, quantitation, and multiplexing of contrast enhancement by MR imaging probes. Magn Reson Med 77:970-978, 2017. © 2016 International Society for Magnetic Resonance in Medicine.


Assuntos
Algoritmos , Meios de Contraste/análise , Imagem por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos , Imagem Molecular/métodos , Técnicas de Sonda Molecular , Meios de Contraste/química , Imagem por Ressonância Magnética/instrumentação , Imagens de Fantasmas , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
8.
BDJ Open ; 3: 17001, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29607074

RESUMO

OBJECTIVES/AIMS: Health Education England (HEE) London developed an innovative 2-year pilot educational and training initiative for enhancing skills in periodontology for dentists and dental hygienists/therapists in 2011. This study explores the perceptions and experiences of those involved in initiating, designing, delivering and participating in this interprofessional approach to training. MATERIALS AND METHODS: Semi-structured qualitative interviews were conducted with a purposive sample of key stakeholders including course participants (dentists and dental hygienists and/or therapists), education and training commissioners, and providers towards the end of the 2-year programme. Interviews, based on a topic guide informed by health services and policy literature, were audio-recorded and transcribed verbatim. Data were analysed based on framework methodology, using QSR NVivo 9 software to manage the data. RESULTS: Twenty-two people were interviewed. Although certain challenges were identified in designing, and teaching, a course bringing together different professional backgrounds and level of skills, the experiences of all key stakeholders were overwhelmingly positive relating to the concept. There was evidence of 'creative interprofessional learning', which led to 'enhancing team working', 'enabling role recognition' and 'equipping participants for delivery of new models of care'. Recommendations emerged with regard to future training and wider health policy, and systems that will enable participants on future enhanced skills courses in periodontology to apply these skills in clinical practice. CONCLUSION: The interprofessional approach to enhanced skills training in periodontology represents an important creative innovation to build capacity within the oral health workforce. This qualitative study has provided a useful insight into the benefits and tensions of an interprofessional model of training from the perspectives of different groups of key stakeholders and suggests its application to other areas of dentistry.

9.
J Am Chem Soc ; 137(28): 9108-16, 2015 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-26083313

RESUMO

Multiple imaging modalities are often required for in vivo imaging applications that require both high probe sensitivity and excellent spatial and temporal resolution. In particular, MR and optical imaging are an attractive combination that can be used to determine both molecular and anatomical information. Herein, we describe the synthesis and in vivo testing of two multimeric NIR-MR contrast agents that contain three Gd(III) chelates and an IR-783 dye moiety. One agent contains a PEG linker and the other a short alkyl linker. These agents label cells with extraordinary efficacy and can be detected in vivo using both imaging modalities. Biodistribution of the PEGylated agent shows observable fluorescence in xenograft MCF7 tumors and renal clearance by MR imaging.


Assuntos
Quelantes/química , Corantes/química , Meios de Contraste/química , Gadolínio/química , Imagem por Ressonância Magnética , Imagem Multimodal , Imagem Óptica , Animais , Quelantes/síntese química , Quelantes/farmacocinética , Corantes/síntese química , Corantes/farmacocinética , Meios de Contraste/síntese química , Meios de Contraste/farmacocinética , Feminino , Gadolínio/farmacocinética , Humanos , Raios Infravermelhos , Células MCF-7 , Camundongos Nus , Neoplasias/diagnóstico , Distribuição Tecidual
10.
Eur J Oral Sci ; 123(1): 39-45, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25521216

RESUMO

There is inconclusive evidence on the value of regular dental attendance. This study explored the relationship between long-term patterns of dental attendance and caries experience. We used retrospective data from 3,235 adults, ≥ 16 yrs of age, who participated in the Adult Dental Health Survey in the UK. Participants were classified into four groups (always, current, former, and never regular-attenders) based on their responses to three questions on lifetime dental-attendance patterns. The association between dental-attendance patterns and caries experience, as measured using the decayed, missing, or filled teeth (DMFT) index, was tested in negative binomial regression models, adjusting for demographic (sex, age, and country of residence) and socio-economic (educational attainment, household income, and social class) factors. A consistent pattern of association between long-term dental attendance and caries experience was found in adjusted models. Former and never regular-attenders had a significantly higher DMFT score and numbers of decayed and missing teeth, but fewer filled teeth, than always regular-attenders. No differences in DMFT or its components were found between current and always regular-attenders. The findings of this study show that adults with different lifetime trajectories of dental attendance had different dental statuses.


Assuntos
Índice CPO , Assistência Odontológica/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Idoso , Cárie Dentária/epidemiologia , Restauração Dentária Permanente/estatística & dados numéricos , Escolaridade , Feminino , Humanos , Renda/estatística & dados numéricos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Sexuais , Classe Social , Perda de Dente/epidemiologia , Reino Unido/epidemiologia , Adulto Jovem
11.
Chem Commun (Camb) ; 50(78): 11469-71, 2014 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-25137290

RESUMO

We describe the design, synthesis and in vitro evaluation of a multimodal and multimeric contrast agent. The agent consists of three macrocyclic Gd(III) chelates conjugated to a fluorophore and possesses high relaxivity, water solubility, and is nontoxic. The modular synthesis is amenable for the incorporation of a variety of fluorophores to generate molecular constructs for a number of applications.


Assuntos
Meios de Contraste/química , Imagem por Ressonância Magnética , Animais , Linhagem Celular Tumoral , Quelantes/química , Meios de Contraste/síntese química , Meios de Contraste/metabolismo , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/metabolismo , Corantes Fluorescentes/química , Gadolínio/química , Células HeLa , Humanos , Camundongos , Microscopia Confocal , Imagem Óptica
12.
J Clin Periodontol ; 41(8): 760-5, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24813815

RESUMO

AIM: To assess whether sense of coherence (SOC) predicts the 4-year incidence of periodontal disease in adults. METHODS: Data from 848 adults who participated in both the Health 2000 Survey and the Follow-Up Study of Finnish Adults' Oral Health were analysed. At baseline, participants provided information on demographic characteristics, education level, the SOC scale, pre-existing diabetes and dental behaviours. The outcome measure was the change in number of teeth with pocketing ≥ 4 mm over 4 years over 4 years. Two separate sets of longitudinal analyses were conducted. The first set was conducted with all the 848 subjects who participated in both surveys and the second set was conducted with the 305 subjects who had no pocketing ≥ 4 mm at baseline. RESULTS: In the full sample, baseline SOC was not associated with change in number of teeth with pocketing over 4 years (coefficient from linear regression: -0.28; 95% CI: -0.74 to 0.18). Similarly, baseline SOC was not associated with number of teeth with pocketing after 4 years (Rate Ratio: 0.94; 95%CI: 0.80 to 1.11) among those with no pocketing at baseline. CONCLUSION: This 4-year prospective study suggests that SOC measured in adulthood does not explain change in the number of teeth with periodontal pocketing ≥ 4 mm.


Assuntos
Doenças Periodontais/epidemiologia , Senso de Coerência , Adulto , Atitude Frente a Saúde , Assistência Odontológica/estatística & dados numéricos , Diabetes Mellitus/epidemiologia , Escolaridade , Feminino , Finlândia/epidemiologia , Seguimentos , Inquéritos Epidemiológicos , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Doenças Periodontais/psicologia , Bolsa Periodontal/epidemiologia , Bolsa Periodontal/psicologia , Estudos Prospectivos , Fumar/epidemiologia , Escovação Dentária/psicologia , Escovação Dentária/estatística & dados numéricos
13.
J Control Release ; 172(3): 812-22, 2013 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-24161382

RESUMO

Our goal was to develop strategies to quantify the accumulation of model therapeutics in small brain metastases using multimodal imaging, in order to enhance the potential for successful treatment. Human melanoma cells were injected into the left cardiac ventricle of immunodeficient mice. Bioluminescent, MR and PET imaging were applied to evaluate the limits of detection and potential for contrast agent extravasation in small brain metastases. A pharmacokinetic model was applied to estimate vascular permeability. Bioluminescent imaging after injecting d-luciferin (molecular weight (MW) 320 D) suggested that tumor cell extravasation had already occurred at week 1, which was confirmed by histology. 7T T1w MRI at week 4 was able to detect non-leaky 100 µm sized lesions and leaky tumors with diameters down to 200 µm after contrast injection at week 5. PET imaging showed that (18)F-FLT (MW 244 Da) accumulated in the brain at week 4. Gadolinium-based MRI tracers (MW 559 Da and 2.066 kDa) extravasated after 5 weeks (tumor diameter 600 µm), and the lower MW agent cleared more rapidly from the tumor (mean apparent permeabilities 2.27 × 10(-5)cm/s versus 1.12 × 10(-5)cm/s). PET imaging further demonstrated tumor permeability to (64)Cu-BSA (MW 65.55 kDa) at week 6 (tumor diameter 700 µm). In conclusion, high field T1w MRI without contrast may improve the detection limit of small brain metastases, allowing for earlier diagnosis of patients, although the smallest lesions detected with T1w MRI were permeable only to d-luciferin and the amphipathic small molecule (18)F-FLT. Different-sized MR and PET contrast agents demonstrated the gradual increase in leakiness of the blood tumor barrier during metastatic progression, which could guide clinicians in choosing tailored treatment strategies.


Assuntos
Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/secundário , Encéfalo/patologia , Melanoma/patologia , Melanoma/secundário , Animais , Benzotiazóis , Meios de Contraste , Feminino , Gadolínio , Humanos , Luminescência , Imagem por Ressonância Magnética , Camundongos , Camundongos SCID , Imagem Multimodal , Imagem Óptica , Permeabilidade , Tomografia por Emissão de Pósitrons
14.
Am J Med Genet A ; 158A(10): 2577-82, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22887808

RESUMO

Primary microcephaly is a genetically heterogeneous condition characterized by reduced head circumference (-3 SDS or more) and mild-to-moderate learning disability. Here, we describe clinical and molecular investigations of a microcephalic child with sensorineural hearing loss. Although consanguinity was unreported initially, detection of 13.7 Mb of copy neutral loss of heterozygosity (cnLOH) on chromosome 9 implicated the CDK5RAP2 gene. Targeted sequencing identified a homozygous E234X mutation, only the third mutation to be described in CDK5RAP2, the first in an individual of non-Pakistani descent. Sensorineural hearing loss is not generally considered to be consistent with autosomal recessive microcephaly and therefore it seems likely that the deafness in this individual is caused by the co-occurrence of a further gene mutation, independent of CDK5RAP2. Nevertheless, further detailed clinical descriptions of rare CDK5RAP2 patients, including hearing assessments will be needed to resolve fully the phenotypic range associated with mutations in this gene. This study also highlights the utility of SNP-array testing to guide disease gene identification where an autosomal recessive condition is plausible.


Assuntos
Códon sem Sentido , Perda Auditiva Neurossensorial/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Microcefalia/genética , Proteínas do Tecido Nervoso/genética , Criança , Feminino , Humanos , Linhagem , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Somália
16.
J Hum Genet ; 57(1): 70-2, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22129557

RESUMO

The development of next generation sequencing (NGS) has radically transformed the scientific landscape, making it possible to sequence the exome of any given individual in a cost-effective way. The power of this approach has been demonstrated by a number of groups who have identified pathogenic mutations in small pedigrees that have been resistant to traditional genetic mapping. Recently it has become clear that exome sequencing has great potential with respect to sporadic disease and the identification of de novo mutations. This is highlighted by studies reporting whole-exome sequencing of patient-parental trios affected by learning disability, autism and schizophrenia. It is widely anticipated that the introduction of this technique into a clinical setting will revolutionise genetic diagnosis. However, the sensitivity of NGS exome sequencing is currently unclear. Here, we describe the exome sequencing of DNA samples from a patient with double cortex syndrome and her parents, resulting in the detection of a mosaic splicing mutation in LIS1. This variant was found at an allele frequency of just 18%, demonstrating that NGS methods have the capacity to identify pathogenic mosaic mutations present at a low level.


Assuntos
Lissencefalias Clássicas e Heterotopias Subcorticais em Banda/genética , Exoma/genética , Frequência do Gene/genética , Mosaicismo , Análise de Sequência de DNA/métodos , 1-Alquil-2-acetilglicerofosfocolina Esterase/química , 1-Alquil-2-acetilglicerofosfocolina Esterase/genética , Sequência de Aminoácidos , Sequência de Bases , Criança , Feminino , Humanos , Imagem por Ressonância Magnética , Proteínas Associadas aos Microtúbulos/química , Proteínas Associadas aos Microtúbulos/genética , Dados de Sequência Molecular
17.
Am J Med Genet A ; 155A(11): 2826-31, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21964664

RESUMO

Neurexin 1 (NRXN1) is a cell adhesion protein, the normal function of which is critical for effective neurotransmission. It forms a trans-synaptic complex in the central nervous system with neuroligin. There has been one case in the literature of a patient with a heterozygous deletion in NRXN1 on one allele and a nonsense mutation on the other allele, reported to have a Pitt Hopkins-like phenotype. We report on two daughters of healthy, nonconsanguineous, Caucasian parents with biallelic NRXN1 deletions identified by array CGH. The children presented with severe early onset epilepsy, profound developmental delay, gastroesophageal reflux disease, constipation, and early onset puberty. Our report confirms that biallelic NRXN1 mutations result in a severe recessive mental retardation syndrome and broadens the range of phenotypes associated with this gene.


Assuntos
Moléculas de Adesão Celular Neuronais/genética , Deleção Cromossômica , Epilepsia/genética , Proteínas do Tecido Nervoso/genética , Adolescente , Alelos , Criança , Cromossomos Humanos Par 2/genética , Cromossomos Humanos Par 5/genética , Hibridização Genômica Comparativa , Constipação Intestinal/genética , Constipação Intestinal/patologia , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/patologia , Epilepsia/patologia , Feminino , Refluxo Gastroesofágico/genética , Refluxo Gastroesofágico/patologia , Heterozigoto , Humanos , Lactente , Padrões de Herança , Puberdade Precoce/genética , Puberdade Precoce/patologia , Deleção de Sequência , Irmãos
18.
J Am Chem Soc ; 133(14): 5329-37, 2011 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-21413801

RESUMO

We have developed a modular architecture for preparing high-relaxivity multiplexed probes utilizing click chemistry. Our system incorporates azide bearing Gd(III) chelates and a trialkyne scaffold with a functional group for subsequent modification. In optimizing the relaxivity of this new complex, we undertook a study of the linker length between a chelate and the scaffold to determine its effect on relaxivity. The results show a strong dependence on flexibility between the individual chelates and the scaffold with decreasing linker length leading to significant increases in relaxivity. Nuclear magnetic resonance dispersion (NMRD) spectra were obtained to confirm a 10-fold increase in the rotational correlation time from 0.049 to 0.60 ns at 310 K. We have additionally obtained a crystal structure demonstrating that modification with an azide does not impact the coordination of the lanthanide. The resulting multinuclear center has a 500% increase in per Gd (or ionic) relaxivity at 1.41 T versus small molecule contrast agents and a 170% increase in relaxivity at 9.4 T.


Assuntos
Meios de Contraste/química , Meios de Contraste/síntese química , Desenho de Drogas , Alquinos/química , Azidas/química , Quelantes/química , Química Click , Gadolínio/química , Imagem por Ressonância Magnética , Modelos Moleculares , Conformação Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Temperatura Ambiente
20.
Annu Rev Med ; 60: 55-68, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-18928333

RESUMO

Recent evidence indicates that the brain can remodel after stroke, primarily through synaptogenesis. Task-specific and repetitive exercise appear to be key factors in promoting synaptogenesis and are central elements in rehabilitation of motor weakness following stroke. Expert medical management ensures a patient is well enough to participate in rehabilitation with minimal distractions due to pain or depression. Contraint-induced motor therapy and body-weight-supported ambulation are forms of exercise that "force use" of an impaired upper extremity. Technologies now in common use include robotics, functional electrical stimulation, and, to a lesser degree, transcranial magnetic stimulation and virtual reality. The data on pharmacological interventions are mixed but encouraging; it is hoped such treatments will directly stimulate brain tissue to recovery. Mitigation of factors preventing movement, such as spasticity, might also play a role. Research evaluating these motor recovery strategies finds them generally good at the movement level but somewhat less robust when looking at functional performance. It remains unclear whether inconsistent evidence for functional improvement is a matter of poor treatment efficacy or insensitive outcome measures.


Assuntos
Destreza Motora , Reabilitação do Acidente Vascular Cerebral , Humanos , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/fisiopatologia
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