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1.
Age Ageing ; 53(3)2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38520141

RESUMO

IMPORTANCE: Sarcopenia, the age-related loss of muscle mass and strength/function, is an important clinical condition. However, no international consensus on the definition exists. OBJECTIVE: The Global Leadership Initiative in Sarcopenia (GLIS) aimed to address this by establishing the global conceptual definition of sarcopenia. DESIGN: The GLIS steering committee was formed in 2019-21 with representatives from all relevant scientific societies worldwide. During this time, the steering committee developed a set of statements on the topic and invited members from these societies to participate in a two-phase International Delphi Study. Between 2022 and 2023, participants ranked their agreement with a set of statements using an online survey tool (SurveyMonkey). Statements were categorised based on predefined thresholds: strong agreement (>80%), moderate agreement (70-80%) and low agreement (<70%). Statements with strong agreement were accepted, statements with low agreement were rejected and those with moderate agreement were reintroduced until consensus was reached. RESULTS: 107 participants (mean age: 54 ± 12 years [1 missing age], 64% men) from 29 countries across 7 continents/regions completed the Delphi survey. Twenty statements were found to have a strong agreement. These included; 6 statements on 'general aspects of sarcopenia' (strongest agreement: the prevalence of sarcopenia increases with age (98.3%)), 3 statements on 'components of sarcopenia' (muscle mass (89.4%), muscle strength (93.1%) and muscle-specific strength (80.8%) should all be a part of the conceptual definition of sarcopenia)) and 11 statements on 'outcomes of sarcopenia' (strongest agreement: sarcopenia increases the risk of impaired physical performance (97.9%)). A key finding of the Delphi survey was that muscle mass, muscle strength and muscle-specific strength were all accepted as 'components of sarcopenia', whereas impaired physical performance was accepted as an 'outcome' rather than a 'component' of sarcopenia. CONCLUSION AND RELEVANCE: The GLIS has created the first global conceptual definition of sarcopenia, which will now serve to develop an operational definition for clinical and research settings.


Assuntos
Sarcopenia , Masculino , Humanos , Idoso , Feminino , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Técnica Delphi , Consenso , Liderança , Força Muscular/fisiologia
2.
Cereb Cortex ; 32(24): 5698-5715, 2022 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-35235645

RESUMO

Genetic variations affecting dopaminergic neuromodulation such as the DRD2/ANKK1 and the COMT Val158Met polymorphisms contribute to goal-directed behavior that requires a balance between stabilization and updating of current states and behaviors. Dopamine is also thought to be relevant for encoding of surprise signals to sensory input and adaptive learning. A link between goal-directed behavior and learning from surprise is therefore plausible. In the present fMRI study, we investigated whether DRD2 and COMT polymorphisms are related to behavioral responses and neural signals in the caudate nucleus and dlPFC during updating or stabilizing internal models of predictable digit sequences. To-be-detected switches between sequences and to-be-ignored digit omissions within a sequence varied by information-theoretic quantities of surprise and entropy. We found that A1 noncarriers and Val-carriers showed a lower response threshold along with increased caudate and dlPFC activation to surprising switches compared with A1-carriers and Met-homozygotes, whose dlPFC activity increased with decreasing switch surprise. In contrast, there were overall smaller differences in behavioral and neural modulation by drift surprise. Our results suggest that the impact of dopamine-relevant polymorphisms in the flexibility-stability trade-off may result in part from the role of dopamine in encoding the weight afforded to events requiring updating or stabilization.


Assuntos
Catecol O-Metiltransferase , Dopamina , Catecol O-Metiltransferase/genética , Receptores de Dopamina D2/genética , Polimorfismo de Nucleotídeo Único , Núcleo Caudado/diagnóstico por imagem , Genótipo
3.
J Emerg Med ; 62(5): 585-589, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35181186

RESUMO

BACKGROUND: In 2014, the Geriatric Emergency Department (GED) Guidelines were published and endorsed by four major medical organizations. The multidisciplinary GED Guidelines characterized the complex needs of the older emergency department (ED) patient and current best practices, with the goal of promoting more cost-effective and patient-centered care. The recommendations are extensive and most EDs then and now have neither the resources nor the hospital administrative support to provide this additional service. DISCUSSION: At the 2021 American Academy of Emergency Medicine's Scientific Assembly, a panel of emergency physicians and geriatricians discussed the GED Guidelines and the current realities of EDs' capacity to provide best practice and guideline-recommended care of GED patients. This article is a synthesis of the panel's presentation and discussion. With the substantial challenges in providing guideline-recommended care in EDs, this article will explore three high-impact GED clinical conditions to highlight guideline recommendations, challenges, and opportunities, and discuss realistically achievable expectations for non-GED-accredited institutions. CONCLUSIONS: In 2014, the GED Guidelines were published, describing the current best practices for GED patients. Unfortunately, most of the EDs worldwide do not provide the level of service recommended by the GED Guidelines. The GED Guidelines can best be termed aspirational for U.S. EDs at the present time.


Assuntos
Medicina de Emergência , Geriatria , Idoso , Serviço Hospitalar de Emergência , Hospitais , Humanos , Motivação , Estados Unidos
4.
Hum Brain Mapp ; 42(4): 1013-1033, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33165996

RESUMO

Stroke patients suffering from hemiparesis may show substantial recovery in the first months poststroke due to neural reorganization. While reorganization driving improvement of upper hand motor function has been frequently investigated, much less is known about the changes underlying recovery of lower limb function. We, therefore, investigated neural network dynamics giving rise to movements of both the hands and feet in 12 well-recovered left-hemispheric chronic stroke patients and 12 healthy participants using a functional magnetic resonance imaging sparse sampling design and dynamic causal modeling (DCM). We found that the level of neural activity underlying movements of the affected right hand and foot positively correlated with residual motor impairment, in both ipsilesional and contralesional premotor as well as left primary motor (M1) regions. Furthermore, M1 representations of the affected limb showed significantly stronger increase in BOLD activity compared to healthy controls and compared to the respective other limb. DCM revealed reduced endogenous connectivity of M1 of both limbs in patients compared to controls. However, when testing for the specific effect of movement on interregional connectivity, interhemispheric inhibition of the contralesional M1 during movements of the affected hand was not detected in patients whereas no differences in condition-dependent connectivity were found for foot movements compared to controls. In contrast, both groups featured positive interhemispheric M1 coupling, that is, facilitation of neural activity, mediating movements of the affected foot. These exploratory findings help to explain why functional recovery of the upper and lower limbs often develops differently after stroke, supporting limb-specific rehabilitative strategies.


Assuntos
Conectoma , Pé/fisiopatologia , Mãos/fisiopatologia , Atividade Motora/fisiologia , Córtex Motor/fisiopatologia , Rede Nervosa/fisiopatologia , Paresia/fisiopatologia , Recuperação de Função Fisiológica/fisiologia , Acidente Vascular Cerebral/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Motor/diagnóstico por imagem , Rede Nervosa/diagnóstico por imagem , Paresia/diagnóstico por imagem , Paresia/etiologia , Projetos Piloto , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem
5.
Neuroimage ; 212: 116674, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32097724

RESUMO

The brain's sensitivity to and accentuation of unpredicted over predicted sensory signals plays a fundamental role in learning. According to recent theoretical models of the predictive coding framework, dopamine is responsible for balancing the interplay between bottom-up input and top-down predictions by controlling the precision of surprise signals that guide learning. Using functional MRI, we investigated whether patients with Parkinson's disease (PD) show impaired learning from prediction errors requiring either adaptation or stabilisation of current predictions. Moreover, we were interested in whether deficits in learning over a specific time scale would be accompanied by altered surprise responses in dopamine-related brain structures. To this end, twenty-one PD patients tested on and off dopaminergic medication and twenty-one healthy controls performed a digit prediction paradigm. During the task, violations of sequence-based predictions either signalled the need to update or to stabilise the current prediction and, thus, to react to them or ignore them, respectively. To investigate contextual adaptation to prediction errors, the probability (or its inverse, surprise) of the violations fluctuated across the experiment. When the probability of prediction errors over a specific time scale increased, healthy controls but not PD patients off medication became more flexible, i.e., error rates at violations requiring a motor response decreased in controls but increased in patients. On the neural level, this learning deficit in patients was accompanied by reduced signalling in the substantia nigra and the caudate nucleus. In contrast, differences between the groups regarding the probabilistic modulation of behaviour and neural responses were much less pronounced at prediction errors requiring only stabilisation but no adaptation. Interestingly, dopaminergic medication could neither improve learning from prediction errors nor restore the physiological, neurotypical pattern. Our findings point to a pivotal role of dysfunctions of the substantia nigra and caudate nucleus in deficits in learning from flexibility-demanding prediction errors in PD. Moreover, the data witness poor effects of dopaminergic medication on learning in PD.


Assuntos
Antiparkinsonianos/uso terapêutico , Encéfalo/fisiopatologia , Aprendizagem/fisiologia , Doença de Parkinson/fisiopatologia , Adaptação Fisiológica/efeitos dos fármacos , Adaptação Fisiológica/fisiologia , Adulto , Idoso , Encéfalo/efeitos dos fármacos , Feminino , Humanos , Aprendizagem/efeitos dos fármacos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/tratamento farmacológico
6.
J Natl Compr Canc Netw ; 17(3): 202-210, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30865919

RESUMO

The NCCN Guidelines for Pancreatic Adenocarcinoma discuss the diagnosis and management of adenocarcinomas of the exocrine pancreas and are intended to assist with clinical decision-making. These NCCN Guidelines Insights discuss important updates to the 2019 version of the guidelines, focusing on postoperative adjuvant treatment of patients with pancreatic cancers.


Assuntos
Adenocarcinoma/diagnóstico , Adenocarcinoma/terapia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Gerenciamento Clínico , Humanos
8.
JAMA ; 322(10): 946-956, 2019 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-31503309

RESUMO

Importance: Disability persists after hip fracture in older persons. Current rehabilitation may not be sufficient to restore ability to walk in the community. Objective: To compare a multicomponent home-based physical therapy intervention (training) with an active control on ability to walk in the community. Design, Setting, and Participants: Parallel, 2-group randomized clinical trial conducted at 3 US clinical centers (Arcadia University, University of Connecticut Health Center, and University of Maryland, Baltimore). Randomization began on September 16, 2013, and ended on June 20, 2017; follow-up ended on October 17, 2017. Patients aged 60 years and older were enrolled after nonpathologic, minimal trauma hip fracture, if they were living in the community and walking without human assistance before the fracture, were assessed within 26 weeks of hospitalization, and were not able to walk during daily activities at the time of enrollment. A total of 210 participants were randomized and reassessed 16 and 40 weeks later. Interventions: The training intervention (active treatment) (n = 105) included aerobic, strength, balance, and functional training. The active control group (n = 105) received transcutaneous electrical nerve stimulation and active range-of-motion exercises. Both groups received 2 to 3 home visits from a physical therapist weekly for 16 weeks; nutritional counseling; and daily vitamin D (2000 IU), calcium (600 mg), and multivitamins. Main Outcomes and Measures: The primary outcome (community ambulation) was defined as walking 300 m or more in 6 minutes at 16 weeks after randomization. The study was designed to test a 1-sided hypothesis of superiority of training compared with active control. Results: Among 210 randomized participants (mean age, 80.8 years; 161 women [76.7%]), 197 (93.8%) completed the trial (187 [89.0%] by completing the 6-minute walk test at 16 weeks and 10 [4.8%] by adjudication of the primary outcome). Among these, 22 of 96 training participants (22.9%) and 18 of 101 active control participants (17.8%) (difference, 5.1% [1-sided 97.5% CI, -∞ to 16.3%]; 1-sided P = .19) became community ambulators. Seventeen training participants (16.2%) and 15 control participants (14.3%) had 1 or more reportable adverse events during the intervention period. The most common reportable adverse events reported were falls (training: 6 [5.7%], control: 4 [3.8%]), femur/hip fracture (2 in each group), pneumonia (training: 2, control: 0), urinary tract infection (training: 2, control: 0), dehydration (training: 0, control: 2), and dyspnea (training: 0, control: 2). Conclusions and Relevance: Among older adults with a hip fracture, a multicomponent home-based physical therapy intervention compared with an active control that included transcutaneous electrical nerve stimulation and active range-of-motion exercises did not result in a statistically significant improvement in the ability to walk 300 m or more in 6 minutes after 16 weeks. Trial Registration: ClinicalTrials.gov Identifier: NCT01783704.


Assuntos
Fraturas do Quadril/reabilitação , Modalidades de Fisioterapia , Idoso , Idoso de 80 Anos ou mais , Terapia por Exercício/métodos , Feminino , Serviços de Assistência Domiciliar , Humanos , Masculino , Amplitude de Movimento Articular , Estimulação Elétrica Nervosa Transcutânea , Teste de Caminhada
9.
Hum Brain Mapp ; 39(9): 3473-3486, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29700893

RESUMO

Evidence from neuropsychological and imaging studies indicate that action and semantic knowledge about tools draw upon distinct neural substrates, but little is known about the underlying interregional effective connectivity. With fMRI and dynamic causal modeling (DCM) we investigated effective connectivity in the left-hemisphere (LH) while subjects performed (i) a function knowledge and (ii) a value knowledge task, both addressing semantic tool knowledge, and (iii) a manipulation (action) knowledge task. Overall, the results indicate crosstalk between action nodes and semantic nodes. Interestingly, effective connectivity was weakened between semantic nodes and action nodes during the manipulation task. Furthermore, pronounced modulations of effective connectivity within the fronto-parietal action system of the LH (comprising lateral occipito-temporal cortex, intraparietal sulcus, supramarginal gyrus, inferior frontal gyrus) were observed in a bidirectional manner during the processing of action knowledge. In contrast, the function and value knowledge tasks resulted in a significant strengthening of the effective connectivity between visual cortex and fusiform gyrus. Importantly, this modulation was present in both semantic tasks, indicating that processing different aspects of semantic knowledge about tools evokes similar effective connectivity patterns. Data revealed that interregional effective connectivity during the processing of tool knowledge occurred in a bidirectional manner with a weakening of connectivity between areas engaged in action and semantic knowledge about tools during the processing of action knowledge. Moreover, different semantic tool knowledge tasks elicited similar effective connectivity patterns.


Assuntos
Córtex Cerebral/fisiologia , Conectoma , Dominância Cerebral/fisiologia , Rede Nervosa/fisiologia , Desempenho Psicomotor/fisiologia , Semântica , Comportamento de Utilização de Ferramentas/fisiologia , Adolescente , Adulto , Equipamentos e Provisões/economia , Feminino , Mãos/fisiologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Adulto Jovem
10.
Hum Brain Mapp ; 39(3): 1078-1092, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29193484

RESUMO

Stroke patients with motor deficits typically feature enhanced neural activity in several cortical areas when moving their affected hand. However, also healthy subjects may show higher levels of neural activity in tasks with higher motor demands. Therefore, the question arises to what extent stroke-related overactivity reflects performance-level-associated recruitment of neural resources rather than stroke-induced neural reorganization. We here investigated which areas in the lesioned brain enable the flexible adaption to varying motor demands compared to healthy subjects. Accordingly, eleven well-recovered left-hemispheric chronic stroke patients were scanned using functional magnetic resonance imaging. Motor system activity was assessed for fist closures at increasing movement frequencies performed with the affected/right or unaffected/left hand. In patients, an increasing movement rate of the affected hand was associated with stronger neural activity in ipsilesional/left primary motor cortex (M1) but unlike in healthy controls also in contralesional/right dorsolateral premotor cortex (PMd) and contralesional/right superior parietal lobule (SPL). Connectivity analyses using dynamic causal modeling revealed stronger coupling of right SPL onto affected/left M1 in patients but not in controls when moving the affected/right hand independent of the movement speed. Furthermore, coupling of right SPL was positively coupled with the "active" ipsilesional/left M1 when stroke patients moved their affected/right hand with increasing movement frequency. In summary, these findings are compatible with a supportive role of right SPL with respect to motor function of the paretic hand in the reorganized brain.


Assuntos
Isquemia Encefálica/fisiopatologia , Encéfalo/fisiopatologia , Atividade Motora/fisiologia , Acidente Vascular Cerebral/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Isquemia Encefálica/diagnóstico por imagem , Mapeamento Encefálico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transtornos dos Movimentos/diagnóstico por imagem , Transtornos dos Movimentos/etiologia , Transtornos dos Movimentos/fisiopatologia , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Acidente Vascular Cerebral/diagnóstico por imagem
11.
Dev Biol ; 416(1): 255-265, 2016 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-27266404

RESUMO

The enteric nervous system (ENS) is required for peristalsis of the gut and is derived from Enteric Neural Crest Cells (ENCCs). During ENS development, the RET receptor tyrosine kinase plays a critical role in the proliferation and survival of ENCCs, their migration along the developing gut, and differentiation into enteric neurons. Mutations in RET and its ligand GDNF cause Hirschsprung disease (HSCR), a complex genetic disorder in which ENCCs fail to colonize variable lengths of the distal bowel. To identify key regulators of ENCCs and the pathways underlying RET signaling, gene expression profiles of untreated and GDNF-treated ENCCs from E14.5 mouse embryos were generated. ENCCs express genes that are involved in both early and late neuronal development, whereas GDNF treatment induced neuronal maturation. Predicted regulators of gene expression in ENCCs include the known HSCR genes Ret and Sox10, as well as Bdnf, App and Mapk10. The regulatory overlap and functional interactions between these genes were used to construct a regulatory network that is underlying ENS development and connects to known HSCR genes. In addition, the adenosine receptor A2a (Adora2a) and neuropeptide Y receptor Y2 (Npy2r) were identified as possible regulators of terminal neuronal differentiation in GDNF-treated ENCCs. The human orthologue of Npy2r maps to the HSCR susceptibility locus 4q31.3-q32.3, suggesting a role for NPY2R both in ENS development and in HSCR.


Assuntos
Sistema Nervoso Entérico/embriologia , Regulação da Expressão Gênica no Desenvolvimento , Doença de Hirschsprung/embriologia , Doença de Hirschsprung/genética , Crista Neural/embriologia , Animais , Antígenos de Diferenciação , Separação Celular , Feminino , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-ret/metabolismo , Transdução de Sinais , Transcriptoma
12.
Neuroimage ; 161: 94-103, 2017 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-28822751

RESUMO

Past attempts to identify the neural substrates of hand and finger imitation skills in the left hemisphere of the brain have yielded inconsistent results. Here, we analyse those associations in a large sample of 257 left hemisphere stroke patients. By introducing novel Bayesian methods, we characterise lesion symptom associations at three levels: the voxel-level, the single-region level (using anatomically defined regions), and the region-pair level. The results are inconsistent across those three levels and we argue that each level of analysis makes assumptions which constrain the results it can produce. Regardless of the inconsistencies across levels, and contrary to past studies which implicated differential neural substrates for hand and finger imitation, we find no consistent voxels or regions, where damage affects one imitation skill and not the other, at any of the three analysis levels. Our novel Bayesian approach indicates that any apparent differences appear to be driven by an increased sensitivity of hand imitation skills to lesions that also impair finger imitation. In our analyses, the results of the highest level of analysis (region-pairs) emphasise a role of the primary somatosensory and motor cortices, and the occipital lobe in imitation. We argue that this emphasis supports an account of both imitation tasks based on direct sensor-motor connections, which throws doubt on past accounts which imply the need for an intermediate (e.g. body-part-coding) system of representation.


Assuntos
Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Gestos , Mãos/fisiopatologia , Comportamento Imitativo/fisiologia , Modelos Teóricos , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/fisiopatologia , Adulto , Idoso , Teorema de Bayes , Córtex Cerebral/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/diagnóstico por imagem
13.
J Natl Compr Canc Netw ; 15(8): 1028-1061, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28784865

RESUMO

Ductal adenocarcinoma and its variants account for most pancreatic malignancies. High-quality multiphase imaging can help to preoperatively distinguish between patients eligible for resection with curative intent and those with unresectable disease. Systemic therapy is used in the neoadjuvant or adjuvant pancreatic cancer setting, as well as in the management of locally advanced unresectable and metastatic disease. Clinical trials are critical for making progress in treatment of pancreatic cancer. The NCCN Guidelines for Pancreatic Adenocarcinoma focus on diagnosis and treatment with systemic therapy, radiation therapy, and surgical resection.


Assuntos
Adenocarcinoma/diagnóstico , Adenocarcinoma/terapia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Tomada de Decisão Clínica , Terapia Combinada , Gerenciamento Clínico , Humanos , Metástase Neoplásica , Estadiamento de Neoplasias
14.
Mov Disord ; 29(7): 953-9, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24752968

RESUMO

BACKGROUND: Pallidal deep brain stimulation (GPi-DBS) effectively ameliorates idiopathic dystonia, although approximately 15% of patients respond insufficiently. Although various thalamic and subthalamic targets have been suggested for dystonic tremor, no systematic studies have been published on thalamic DBS in dystonic tremor. We assessed the effect of thalamic/subthalamic area DBS (Th-DBS) on dystonic head tremor and dystonia in a single-blind design. METHODS: Dystonic head tremor and dystonia before and 3 months after surgery were quantified via blinded video-ratings using the Fahn-Tolosa-Marin-Tremor-Scale and the Burke-Fahn-Marsden-Dystonia-Rating-Scale in seven patients with idiopathic cervical or segmental dystonia, dystonic head tremor, and bilateral Th-DBS. Pain, side effects, adverse events, and stimulation parameters were assessed. RESULTS: Th-DBS improved dystonic tremor and dystonia (P < 0.05; 57.1% and 70.4%, respectively). Head tremor amplitude and pain were also improved (P < 0.05; 77.5% and 90.0%, respectively). Side effects included dysarthria, gait disturbance, slowness of movement, and weight gain. CONCLUSION: Dystonic head tremor and dystonia can be improved with Th-DBS.


Assuntos
Estimulação Encefálica Profunda , Distonia/terapia , Núcleo Subtalâmico/fisiopatologia , Tremor/terapia , Núcleos Ventrais do Tálamo/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Distonia/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Método Simples-Cego , Resultado do Tratamento , Tremor/etiologia , Adulto Jovem
15.
Development ; 137(5): 775-84, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20147379

RESUMO

The highly related transcription factors Sox4 and Sox11 are expressed in the developing sympathetic nervous system. In the mouse, Sox11 appears first, whereas Sox4 is prevalent later. Using mouse mutagenesis and overexpression strategies in chicken, we studied the role of both SoxC proteins in this tissue. Neither Sox4 nor Sox11 predominantly functioned by promoting pan-neuronal or noradrenergic differentiation of sympathetic neurons as might have been expected from studies in neuronal precursors of the central nervous system. The transcriptional network that regulates the differentiation of sympathetic neurons remained intact and expression of noradrenergic markers showed only minor alterations. Instead, Sox11 was required in early sympathetic ganglia for proliferation of tyrosine hydroxylase-expressing cells, whereas Sox4 ensured the survival of these cells at later stages. In the absence of both Sox4 and Sox11, sympathetic ganglia remained hypoplastic throughout embryogenesis because of consecutive proliferation and survival defects. As a consequence, sympathetic ganglia were rudimentary in the adult and sympathetic innervation of target tissues was impaired leading to severe dysautonomia.


Assuntos
Fatores de Transcrição SOXC/fisiologia , Sistema Nervoso Simpático/embriologia , Animais , Linhagem da Célula/genética , Embrião de Galinha , Embrião de Mamíferos , Regulação da Expressão Gênica no Desenvolvimento , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurogênese/genética , Norepinefrina/metabolismo , Fatores de Transcrição SOXC/genética , Fatores de Transcrição SOXC/metabolismo , Sistema Nervoso Simpático/metabolismo , Fatores de Tempo
16.
Alzheimers Dement (N Y) ; 9(4): e12422, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37841653

RESUMO

INTRODUCTION: The risk reduction for Alzheimer's disease (rrAD) trial was a multisite clinical trial to assess exercise and intensive vascular pharmacological treatment on cognitive function in community-dwelling older adults at increased risk for Alzheimer's disease. METHODS: Eligibility, consent, and randomization rates across different referral sources were compared. Informal interviews conducted with each site's project team were conducted upon study completion. RESULTS: Initially, 3290 individuals were screened, of whom 28% were eligible to consent, 805 consented to participate (87.2% of those eligible), and 513 (36.3% of those consented) were randomized. Emails sent from study site listservs/databases yielded the highest amount (20.9%) of screened individuals. Professional referrals from physicians yielded the greatest percentage of consented individuals (57.1%). Referrals from non-professional contacts (ie, friends, family; 75%) and mail/phone contact from a site (73.8%) had the highest yield of randomization. DISCUSSION: Professional referrals or email from listservs/registries were most effective for enrolling participants. The greatest yield of eligible/randomized participants came from non-professional and mail/phone contacts. Future trials should consider special efforts targeting these recruitment approaches. Highlights: Clinical trial recruitment is commonly cited as a significant barrier to advancing our understanding of cognitive health interventions.The most cited referral source was email, followed by interviews/editorials on the radio, television, local newspapers, newsletters, or magazine articles.The referral method that brought in the largest number of contacts was email but did not result in the greatest yield of consents or eligible participants.The sources that yielded the greatest likelihood of consent were professional referrals (ie, physician), social media, and mail/phone contact from study site.The greatest yield of eligible/randomized participants came from non-professional contacts and mail/phone contact from a site.Findings suggest that sites may need to focus on more selective referral sources, such as using contact mailing and phone lists, rather than more widely viewed recruitment sources, such as social media or TV/radio advertisements.

17.
J Neurosci ; 31(17): 6379-91, 2011 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-21525278

RESUMO

Neural crest stem cells (NCSCs) give rise to the neurons and glia of the peripheral nervous system (PNS). NCSC-like cells can be isolated from multiple peripheral organs and maintained in neurosphere culture. Combining in vitro culture and transplantation, we show that expanded embryonic NCSC-like cells lose PNS traits and are reprogrammed to generate CNS cell types. When transplanted into the embryonic or adult mouse CNS, they differentiate predominantly into cells of the oligodendrocyte lineage without any signs of tumor formation. NCSC-derived oligodendrocytes generate CNS myelin and contribute to the repair of the myelin deficiency in shiverer mice. These results demonstrate a reprogramming of PNS progenitors to CNS fates without genetic modification and imply that PNS cells could be a potential source for cell-based CNS therapy.


Assuntos
Lesões Encefálicas/cirurgia , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Bainha de Mielina/metabolismo , Células-Tronco Neurais/fisiologia , Oligodendroglia/fisiologia , Transplante de Células-Tronco/métodos , Animais , Animais Recém-Nascidos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Lesões Encefálicas/metabolismo , Lesões Encefálicas/fisiopatologia , Diferenciação Celular/fisiologia , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Células Cultivadas , Modelos Animais de Doenças , Embrião de Mamíferos , Feminino , Gânglios Espinais/citologia , Proteína Glial Fibrilar Ácida/metabolismo , Proteínas de Fluorescência Verde/genética , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas Associadas aos Microtúbulos/metabolismo , Proteína Básica da Mielina/genética , Proteína Básica da Mielina/metabolismo , Proteína Proteolipídica de Mielina/genética , Proteína Proteolipídica de Mielina/metabolismo , Bainha de Mielina/ultraestrutura , Proteínas do Tecido Nervoso/metabolismo , Proteínas de Neurofilamentos/metabolismo , Antígenos O/metabolismo , Fator de Transcrição 2 de Oligodendrócitos , Oligodendroglia/ultraestrutura , Transfecção/métodos , Tubulina (Proteína)/metabolismo
18.
Eur J Appl Physiol ; 112(3): 1123-31, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21748366

RESUMO

We hypothesized that treatment with testosterone (T) and recombinant human growth hormone (rhGH) would increase lean mass (LM) and muscle strength proportionally and an in a linear manner over 16 weeks. This was a multicenter, randomized, controlled, double-masked investigation of T and rhGH supplementation in older (71 ± 4 years) community-dwelling men. Participants received transdermal T at either 5 or 10 g/day as well as rhGH at 0, 3.0 or 5.0 µg/kg/day for 16 weeks. Body composition was determined by dual-energy X-ray absorptiometry (DEXA) and muscle performance by composite one-repetition maximum (1-RM) strength and strength per unit of lean mass (muscle quality, MQ) for five major muscle groups (upper and lower body) at baseline, week 8 and 17. The average change in total LM at study week 8 compared with baseline was 1.50 ± 1.54 kg (P < 0.0001) in the T only group and 2.64 ± 1.7 (P < 0.0001) in the T + rhGH group and at week 17 was 1.46 ± 1.48 kg (P < 0.0001) in the T only group and 2.14 ± 1.96 kg (P < 0.0001) in the T + rhGH group. 1-RM strength improved modestly in both groups combined (12.0 ± 23.9%, P < 0.0001) at week 8 but at week 17 these changes were twofold greater (24.7 ± 31.0%, P < 0.0001). MQ did not significantly change from baseline to week 8 but increased for the entire cohort, T only, and T + rhGH groups by week 17 (P < 0.001). Despite sizeable increases in LM measurements at week 8, tests of muscle performance did not show substantive improvements at this time point.


Assuntos
Desempenho Atlético/fisiologia , Composição Corporal/efeitos dos fármacos , Hormônio do Crescimento Humano/administração & dosagem , Músculo Esquelético/fisiologia , Testosterona/administração & dosagem , Idoso , Composição Corporal/fisiologia , Método Duplo-Cego , Avaliação Geriátrica/métodos , Hormônio do Crescimento Humano/farmacologia , Humanos , Masculino , Força Muscular/efeitos dos fármacos , Força Muscular/fisiologia , Músculo Esquelético/efeitos dos fármacos , Valor Preditivo dos Testes , Testosterona/farmacologia , Magreza/fisiopatologia
19.
J Am Geriatr Soc ; 70(5): 1368-1373, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35277967

RESUMO

In 2014 the Geriatric Emergency Department (GED) Guidelines were published and endorsed by four major medical organizations. The multidisciplinary GED Guidelines characterize the complex needs of the older emergency department (ED) patient and current best practices with the goal of promoting more cost-effective and patient-centered care. The recommendations are extensive and the vast majority of EDs then and now do not have either the resources nor hospital administrative support to provide this additional service. At the 2021 American Academy of Emergency Medicine's Scientific Assembly, a panel of emergency medicine physicians and geriatricians discussed the GED Guidelines and the current realities of EDs' capacity to provide best practice and guideline recommended care of GED patients. This article is a synthesis of the panel's presentation and discussion. With the substantial challenges in providing guideline recommended care in EDs, this article will explore three high impact GED clinical conditions to highlight guideline recommendations, challenges and opportunities, and discuss realistically achievable expectations for non-Geriatric ED accredited institutions. In 2014 the Geriatric Emergency Department Guidelines were published describing the current best practices for geriatric ED patients. Unfortunately, the vast majority of EDs worldwide do not provide the level of service recommended by the GED guidelines. The GED Guidelines can best be termed aspirational for U.S. EDs at the present time.


Assuntos
Medicina de Emergência , Geriatria , Idoso , Serviço Hospitalar de Emergência , Hospitais , Humanos , Motivação
20.
J Am Geriatr Soc ; 70(11): 3087-3095, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35856155

RESUMO

BACKGROUND: Community-dwelling older adults experiencing hip fracture often fail to achieve adequate walking capacity following surgery and rehabilitation. Effects of psychological factors on post-fracture walking capacity are poorly understood. Accordingly, this paper investigates effects of psychological resilience on observed walking capacity measures in older adults following hip fracture, controlling for important covariates. METHODS: Data were drawn from the Community Ambulation Project, a clinical trial of 210 community-dwelling adults aged ≥60 years who experienced a minimal trauma hip fracture and were randomized to one of two 16-week home-based physical therapist-guided interventions. Psychological resilience was measured at study baseline using the 6-item Brief Resilience Scale (BRS); scores were classified into groups in order to distinguish levels of self-reported resilience. Walking capacity was assessed at study baseline and 16 weeks later using 4-Meter Gait Speed (4MGS), 50-Foot Walk Test (50FWT), and 6-Minute Walk Distance (SMWD). In multivariate analyses of covariance in which 16-week follow-up values of each walking measure were outcomes, covariates included clinical trial arm, gender, age, and baseline values of: walking measure corresponding to the outcome; body mass index; depressive symptom severity; degree of psychological optimism; cognitive status; informal caregiver need; and days from hospital admission to randomization. RESULTS: Increases between baseline and 16 weeks later in mean gait speed in meters/sec (m/s) and walking distance in meters (m) in 4MGS, 50FWT and SMWD were 0.06 m/s (p = 0.061), 0.11 m/s (p < 0.01), and 25.5 m (p = 0.056) greater, respectively, in the most resilient BRS group compared to the least resilient BRS group. CONCLUSION: Higher levels of psychological resilience were associated with greater walking speed and distance. Psychological resilience represents a potentially clinically important pathway and intervention target, toward the goal of improving walking capacity among older adults known to have substantial residual disability following hip fracture.


Assuntos
Fraturas do Quadril , Resiliência Psicológica , Humanos , Idoso , Caminhada , Fraturas do Quadril/cirurgia , Fraturas do Quadril/reabilitação , Velocidade de Caminhada , Teste de Caminhada
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