RESUMO
A new activity for the [NiFe] uptake hydrogenaseâ 1 of Escherichia coli (Hyd1) is presented. Direct reduction of biological flavin cofactors FMN and FAD is achieved using H2 as a simple, completely atom-economical reductant. The robust nature of Hyd1 is exploited for flavin reduction across a broad range of temperatures (25-70 °C) and extended reaction times. The utility of this system as a simple, easy to implement FMNH2 or FADH2 regenerating system is then demonstrated by supplying reduced flavin to Old Yellow Enzyme "ene-reductases" to support asymmetric alkene reductions with up to 100 % conversion. Hyd1 turnover frequencies up to 20.4â min-1 and total turnover numbers up to 20 200 were recorded during flavin recycling.
Assuntos
Alcenos/metabolismo , Escherichia coli/enzimologia , Flavinas/metabolismo , Hidrogenase/metabolismo , Oxirredutases/metabolismo , Alcenos/química , Biocatálise , Flavinas/química , Hidrogenase/química , Hidrogenação , Estrutura Molecular , Oxirredução , Oxirredutases/químicaRESUMO
Vinyl cations derived from diazo ketones participate in transition-metal-free C-H insertion reactions, but the corresponding amide and ester analog exhibit divergent reactivity profiles. Whereas cations formed from diazo ketones undergo a rearrangement and C-H insertion sequence, those from diazo amides do so less efficiently and tend to be competitively trapped before the insertion step occurs. Diazo esters undergo several rearrangement steps and fail to insert. DFT calculations reveal that this disparity stems from two factors: differing levels of electrostatic stabilization of the initially formed vinyl cation by the adjacent carbonyl oxygen and predistortion of the ketone and amide systems toward C-H insertion. The computational data is in strong agreement with experimental results, and this study explains how structural and electronic factors determine the outcome of reactions of diazo carbonyl-derived vinyl cations.
Assuntos
Amidas/química , Compostos de Diazônio/química , Ésteres/química , Cetonas/química , Elementos de Transição/química , Teoria da Densidade Funcional , Estrutura MolecularRESUMO
The Lewis acid-promoted generation of destabilized vinyl cations from ß-hydroxy diazo ketones leads to an energetically favorable 1,2-shift across the alkene followed by an irreversible C-H insertion to give cyclopentenone products. This reaction sequence overcomes typical challenges of counter-ion trapping and rearrangement reversibility of vinyl cations and has been used to study the migratory aptitudes of nonequivalent substituents in an uncommon C(sp2) to C(sp) vinyl cation rearrangement. The migratory aptitude trends were consistent with those observed in other cationic rearrangements; the substituent that can best stabilize a cation more readily migrates. However, density functional theory calculations show that the situation is more complex. Selectivity in the formation of one conformational isomer of the vinyl cation and facial selective migration across the alkene due to an electrostatic interaction between the vinyl cation and the adjacent carbonyl oxygen work in concert to determine which group migrates. This study provides valuable insight into predicting migration preferences when applying this methodology to the synthesis of structurally complex cyclopentenones that are differentially substituted at the α and ß positions.
Assuntos
Compostos de Vinila/síntese química , Cátions/síntese química , Cátions/química , Cetonas/química , Ácidos de Lewis/química , Estrutura Molecular , Compostos de Vinila/químicaRESUMO
Cleaner synthesis of amines remains a key challenge in organic chemistry because of their prevalence in pharmaceuticals, agrochemicals and synthetic building blocks. Here, we report a different paradigm for chemoselective hydrogenation of nitro compounds to amines, under mild, aqueous conditions. The hydrogenase enzyme releases electrons from H2 to a carbon black support which facilitates nitro-group reduction. For 30 nitroarenes we demonstrate full conversion (isolated yields 78 - 96%), with products including pharmaceuticals benzocaine, procainamide and mesalazine, and 4-aminophenol - precursor to paracetamol (acetaminophen). We also showcase gram-scale synthesis of procainamide with 90% isolated yield. We demonstrate potential for extension to aliphatic substrates. The catalyst is highly selective for reduction of the nitro group over other unsaturated bonds, tolerant to a wide range of functional groups, and exhibits excellent stability in reactions lasting up to 72 hours and full reusability over 5 cycles with a total turnover number over 1 million, indicating scope for direct translation to fine chemical manufacturing.
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This meta-analytic study examined the relationship among the constructs of acculturation, enculturation, and acculturation strategies (i.e., integration, assimilation, separation, marginalization), and mental health. Data from 325 studies (163 journal articles and 162 dissertation studies) were analyzed using a random-effects model, across a broad spectrum of negative mental health (NM: depression, anxiety, psychological distress, and negative affect) and positive mental health (PM: self-esteem, satisfaction with life, and positive affect). Overall, acculturation was favorably associated with both NM (negatively) and PM (positively), whereas enculturation was favorably related only to PM (positively). In fact, enculturation was positively related to anxiety. The specifics of these relations were further examined using the following moderators: (a) researchers' operationalization of acculturation/enculturation (i.e., linearity, dimensionality); (b) contextual influences (i.e., when and where the study was conducted); and (c) sample characteristics (i.e., voluntariness of residency, race, gender, age). Overall, bilinear measures of acculturation indicated a positive association with PM, while unilinear measures did not. External acculturation (e.g., language, behaviors) and internal enculturation (e.g., identity) were most favorably related to mental health. The place of study had differential effects on the relation of enculturation and NM. Acculturation appeared to be especially important to Asian Americans, whereas enculturation was to African Americans. Differential effects of age suggested the need to consider life-span development of needs and social roles in relation to acculturation and enculturation. Both correlational analyses and mean comparisons affirmed that integration was the most favorable acculturation strategy to mental health. Implications for research, practice, and theory are discussed.
Assuntos
Aculturação , Saúde Mental , Adulto , Feminino , Humanos , Masculino , Transtornos Mentais/epidemiologia , Autoimagem , Identificação Social , Estudantes , Inquéritos e Questionários , Estados Unidos/epidemiologiaRESUMO
The present study proposed and tested a conceptual model of acculturation/enculturation and subjective well-being (SWB) by including social connectedness in mainstream society, social connectedness in the ethnic community, perceived discrimination, and expected social status as mediators. Survey data from 273 Asian American college students in the midwest were analyzed by using structural equation modeling. Results indicated that the effect of acculturation on SWB was mediated by social connectedness in mainstream and ethnic communities and expected social status, whereas the effect of enculturation on SWB was mediated by social connectedness in the ethnic community and expected social status. Contrary to the authors' hypothesis, perceived discrimination did not mediate the relation of acculturation and SWB, but indirectly influenced SWB via a lowered sense of connectedness to mainstream society. Approximately 46% of the variance in SWB was accounted for by the variables included in this model. Implications for theory, research, and practice are discussed.
Assuntos
Aculturação , Asiático/psicologia , Emigrantes e Imigrantes/psicologia , Relações Interpessoais , Preconceito , Distância Psicológica , Qualidade de Vida/psicologia , Identificação Social , Adolescente , Adulto , Aspirações Psicológicas , Feminino , Humanos , Masculino , Modelos Psicológicos , Inventário de Personalidade , Psicometria/estatística & dados numéricos , Reprodutibilidade dos Testes , Fatores Socioeconômicos , Estudantes/psicologia , Adulto JovemRESUMO
Age-related remodelling of the arterial wall shifts the load bearing from the compliant elastin network to the stiffer collagen fibres. While this phenomenon has been widely investigated in animal models, human studies are lacking due to shortage of donors' arteries. This work aimed to characterise the effect of ageing on the mechanical properties of the human aortic wall in the circumferential direction. N = 127 thoracic aortic rings (age 18-81 years) were subjected to circumferential tensile testing. The tangential elastic modulus (Kθθθθ) was calculated at pressure-equivalent stresses ranging 60-100 mmHg. Further, the mechanical data were fitted using the Holzpafel-Gasser-Ogden hyperelastic strain energy function (HGO-SEF), modelling the superimposed response of an isotropic matrix (elastin) reinforced by collagen fibres. Kθθθθ increased with age across at all considered pressures (p < 0.001), although more strongly at higher pressures. Indeed, the slope of the linear Kθθθθ-pressure relationship increased by 300% from donors <30 to ≥70 years (4.72± 2.95 to 19.06± 6.82 kPa/mmHg, p < 0.001). The HGO-SEF elastin stiffness-like parameter dropped by 31% between 30 and 40 years (p < 0.05) with non-significant changes thereafter. Conversely, changes in HGO-SEF collagen parameters were observed later at age>60 years, with the exponential constant increasing by â¼20-50 times in the investigated age range (p < 0.001). The results provided evidence that the human thoracic aorta undergoes stiffening during its life-course. Constitutive modelling suggested that these changes in arterial mechanics are related to the different degeneration time-courses of elastin and collagen; likely due to considerable fragmentation of elastin first, with the load bearing shifting from the compliant elastin to the stiffer collagen fibres. This process leads to a gradual impairment of the aortic elastic function with age.
Assuntos
Aorta Torácica , Elastina , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Animais , Aorta Torácica/fisiologia , Fenômenos Biomecânicos , Colágeno , Elastina/fisiologia , Humanos , Testes Mecânicos , Pessoa de Meia-Idade , Estresse Mecânico , Adulto JovemRESUMO
Heterogeneous biocatalytic hydrogenation is an attractive strategy for clean, enantioselective C[double bond, length as m-dash]X reduction. This approach relies on enzymes powered by H2-driven NADH recycling. Commercially available carbon-supported metal (metal/C) catalysts are investigated here for direct H2-driven NAD+ reduction. Selected metal/C catalysts are then used for H2 oxidation with electrons transferred via the conductive carbon support material to an adsorbed enzyme for NAD+ reduction. These chemo-bio catalysts show improved activity and selectivity for generating bioactive NADH under ambient reaction conditions compared to metal/C catalysts. The metal/C catalysts and carbon support materials (all activated carbon or carbon black) are characterised to probe which properties potentially influence catalyst activity. The optimised chemo-bio catalysts are then used to supply NADH to an alcohol dehydrogenase for enantioselective (>99% ee) ketone reductions, leading to high cofactor turnover numbers and Pd and NAD+ reductase activities of 441 h-1 and 2347 h-1, respectively. This method demonstrates a new way of combining chemo- and biocatalysis on carbon supports, highlighted here for selective hydrogenation reactions.
RESUMO
A new activity for the [NiFe] uptake hydrogenaseâ 1 of Escherichia coli (Hyd1) is presented. Direct reduction of biological flavin cofactors FMN and FAD is achieved using H2 as a simple, completely atom-economical reductant. The robust nature of Hyd1 is exploited for flavin reduction across a broad range of temperatures (25-70 °C) and extended reaction times. The utility of this system as a simple, easy to implement FMNH2 or FADH2 regenerating system is then demonstrated by supplying reduced flavin to Old Yellow Enzyme "ene-reductases" to support asymmetric alkene reductions with up to 100 % conversion. Hyd1 turnover frequencies up to 20.4â min-1 and total turnover numbers up to 20 200 were recorded during flavin recycling.
RESUMO
BACKGROUND: Stroke can result in pain and loss of motor control in the hemiplegic shoulder, and while prevention of secondary changes is likely to be the most effective management, there is limited evidence directing clinicians towards the most at-risk patients. OBJECTIVES: The aim of this case series was to investigate the presentation of shoulder pain, motor impairment, shoulder passive range of motion (PROM) and alignment of the hemiplegic shoulder following acute stroke. METHODS: This study reported data that was collected as part of a pilot randomized controlled trial investigating kinesiology taping of the hemiplegic shoulder. Participants with a diagnosis of acute stroke and severe upper limb motor impairment were included. From 24-h post stroke and continuing every three days until discharge, measurements of shoulder pain (visual analogue scale, Ritchie Articular Index), motor impairment (Chedoke McMaster Stroke Assessment), PROM and alignment (both clinical measures) were collected. Clinical trial registry number - ACTRN12615000502538. RESULTS: Of 156 patients screened over six months, 10 of 15 eligible participants were recruited. On initial assessment, three participants reported pain and all had severe upper limb motor impairment. All participants initially demonstrated close to full shoulder PROM. Six participants had shoulder subluxation and five demonstrated scapula malalignment. CONCLUSIONS: Given the severity of upper limb motor impairment, pain and reduced PROM were seen in a small number of participants. The clinical course of shoulder pain and PROM following stroke remains unclear. Large observational studies tracking shoulder characteristics from acute through to rehabilitation settings are needed.
Assuntos
Hemiplegia/etiologia , Atividade Motora/fisiologia , Amplitude de Movimento Articular/fisiologia , Dor de Ombro/etiologia , Ombro/fisiopatologia , Acidente Vascular Cerebral/complicações , Idoso , Fita Atlética , Feminino , Hemiplegia/reabilitação , Humanos , Masculino , Pessoa de Meia-Idade , Projetos de Pesquisa , Dor de Ombro/reabilitação , Acidente Vascular Cerebral/fisiopatologia , Reabilitação do Acidente Vascular Cerebral , Extremidade SuperiorRESUMO
OBJECTIVE: Caring for children in foster or adoptive care with behavioral health needs can severely stress parents, contributing to adverse outcomes for children and families. Trauma-informed services from the child welfare and mental health sectors may help prevent poor outcomes by helping children and parents identify and understand trauma and its impact on children's behavioral health and receive effective treatment. To help understand the role of trauma-informed services for the child welfare population, we examined whether trauma-informed child welfare and mental health services moderated the relationship between children's behavioral health needs and parent satisfaction and commitment. METHOD: The researchers analyzed data from a cross-sectional statewide survey of foster and adoptive parents (n = 512 respondents, 42% of 1,206 contacted) from one state. RESULTS: Foster (but not adoptive) parent ratings of trauma-informed mental health services significantly moderated the relationship between children's behavioral health needs and foster and adoptive parent satisfaction and commitment. As ratings of trauma-informed mental health services increased, the association between child behavioral health needs and parent satisfaction and commitment became nonsignificant, suggesting a buffering effect. Trauma-informed child welfare services did not moderate the relationship for foster or adoptive parents. CONCLUSIONS: Leaders and policymakers are urged to promote trauma-informed mental health services for children involved with child welfare to potentially buffer foster parents against lower parenting satisfaction and commitment. More research is needed to replicate and expand on these findings and to examine the effectiveness of trauma-informed services on other relevant child and family outcomes. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
Assuntos
Adoção/psicologia , Proteção da Criança , Cuidados no Lar de Adoção/psicologia , Serviços de Saúde Mental , Pais/psicologia , Comportamento Problema , Criança , Proteção da Criança/psicologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Poder Familiar/psicologia , Comportamento Problema/psicologia , Qualidade da Assistência à Saúde , Estresse Psicológico/etiologia , Estresse Psicológico/prevenção & controleRESUMO
The recent genome-wide analysis of carotid-femoral pulse wave velocity (PWV) identified a significant locus within the 14q32.2 gene desert. Gene regulatory elements for the transcriptional regulator B-cell CLL/lymphoma 11B (BCL11B) are within this locus and an attractive target for the gene association. We investigated the functional impact of these gene desert SNPs on BCL11B transcript in human aorta to characterize further its role in aortic stiffness. To do this, we used a large repository of aortic tissues (n = 185) from an organ transplant program and assessed ex vivo stiffness of the aortic rings. We tested association of three lead SNPs from the GWAS meta-analysis with ex vivo aortic stiffness and BCL11B aortic mRNA expression: rs1381289 and rs10782490 SNPs associated significantly with PWV and showed allele-specific differences in BCL11B mRNA. The risk alleles associated with lower BCL11B expression, suggesting a protective role for BCL11B. Despite strong association, we could not detect BCL11B protein in the human aorta. However, qPCR for CD markers showed that BCL11B transcript correlated strongly with markers for activated lymphocytes. Our data confirm the significance of the 14q32.2 region as a risk locus for aortic stiffness and an upstream regulator of BCL11B. The BCL11B transcript detected in the human aorta may reflect lymphocyte infiltration, suggesting that immune mechanisms contribute to the observed association of BCL11B with aortic stiffness.
Assuntos
Cromossomos Humanos Par 14/genética , Ativação Linfocitária , Polimorfismo de Nucleotídeo Único , Proteínas Repressoras/genética , Proteínas Supressoras de Tumor/genética , Rigidez Vascular/genética , Adulto , Idoso , Animais , Aorta/metabolismo , Aorta/patologia , Biomarcadores/sangue , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Análise de Onda de Pulso , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Repressoras/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Rigidez Vascular/imunologiaRESUMO
Stiffening of the aorta is an important independent risk factor for myocardial infarction and stroke. Yet its genetics is complex and little is known about its molecular drivers. We have identified for the first time, tagSNPs in the genes for extracellular matrix proteins, aggrecan and fibulin-1, that modulate stiffness in young healthy adults. We confirmed SNP associations with ex vivo stiffness measurements and expression studies in human donor aortic tissues. Both aggrecan and fibulin-1 were found in the aortic wall, but with marked differences in the distribution and glycosylation of aggrecan reflecting loss of chondroitin-sulphate binding domains. These differences were age-dependent but the striking finding was the acceleration of this process in stiff versus elastic young aortas. These findings suggest that aggrecan and fibulin-1 have critical roles in determining the biomechanics of the aorta and their modification with age could underpin age-related aortic stiffening.
Assuntos
Agrecanas , Envelhecimento , Aorta/metabolismo , Proteínas de Ligação ao Cálcio , Polimorfismo de Nucleotídeo Único , Rigidez Vascular/fisiologia , Adolescente , Adulto , Agrecanas/genética , Agrecanas/metabolismo , Envelhecimento/genética , Envelhecimento/metabolismo , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Feminino , Humanos , MasculinoRESUMO
It has been proposed that acute hypothalamo-pituitary-adrenal (HPA) axis challenge using noradrenergic drugs may be of utility in assessing the functional integrity of central noradrenaline pathways. Atomoxetine (formerly tomoxetine) is a highly selective noradrenaline reuptake inhibitor, which has recently been licensed for the treatment of attention deficit hyperactivity disorder (ADHD). The aim of this study was to assess the effects of acute atomoxetine on salivary cortisol levels for the first time.A total of 60 healthy male volunteers received 60 mg atomoxetine, 30 mg citalopram, or placebo per os in a double-blind parallel groups design (n = 20 per group). Salivary cortisol, blood pressure and pulse rates were recorded at baseline and at +1.0, +1.5, +2.5 and +3.5 hours after capsule administration.60 mg atomoxetine led to highly significant increases in salivary cortisol and a moderate increase in pulse rate, in the absence of significant effects on blood pressure. 30 mg citalopram had no significant effects on cortisol or cardiovascular parameters. These data support the utility of atomoxetine neuroendocrine challenge for evaluating central noradrenaline pathways, which may be of future use in neuropsychiatric patient studies. Furthermore, the effects of atomoxetine on HPA axis function may have clinical implications given the use of this agent in the treatment of ADHD.
Assuntos
Inibidores da Captação Adrenérgica/farmacologia , Citalopram/farmacologia , Hidrocortisona/metabolismo , Propilaminas/farmacologia , Saliva/metabolismo , Glândulas Salivares/efeitos dos fármacos , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Administração Oral , Inibidores da Captação Adrenérgica/administração & dosagem , Cloridrato de Atomoxetina , Pressão Sanguínea/efeitos dos fármacos , Cápsulas , Citalopram/administração & dosagem , Método Duplo-Cego , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Testes de Função Adreno-Hipofisária/métodos , Propilaminas/administração & dosagem , Valores de Referência , Glândulas Salivares/metabolismo , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Fatores de TempoRESUMO
We report a Lewis acid catalyzed reaction sequence involving a 1,2-shift and subsequent C-H insertion that gives monocyclic and fused bicyclic cyclopentenone products. This reaction sequence, which is initiated by treating ß-hydroxy-α-diazo ketones with a Lewis acid, proceeds through vinyl cation intermediates that insert at non-activated gamma C-H bonds. This reaction represents an alternative strategy to exploit the diazo functional group in an intramolecular C-H insertion, and can provide products not accessible by transition metal catalyzed C-H insertions. This remote C-H activation process provides good yields of bicyclic cyclopentenone products that contain 7- and 8-membered rings, and monocyclic prostaglandin analogs.
RESUMO
Deletion of exon 9 from Cullin-3 (CUL3, residues 403-459: CUL3(Δ403-459)) causes pseudohypoaldosteronism type IIE (PHA2E), a severe form of familial hyperkalaemia and hypertension (FHHt). CUL3 binds the RING protein RBX1 and various substrate adaptors to form Cullin-RING-ubiquitin-ligase complexes. Bound to KLHL3, CUL3-RBX1 ubiquitylates WNK kinases, promoting their ubiquitin-mediated proteasomal degradation. Since WNK kinases activate Na/Cl co-transporters to promote salt retention, CUL3 regulates blood pressure. Mutations in both KLHL3 and WNK kinases cause PHA2 by disrupting Cullin-RING-ligase formation. We report here that the PHA2E mutant, CUL3(Δ403-459), is severely compromised in its ability to ubiquitylate WNKs, possibly due to altered structural flexibility. Instead, CUL3(Δ403-459) auto-ubiquitylates and loses interaction with two important Cullin regulators: the COP9-signalosome and CAND1. A novel knock-in mouse model of CUL3(WT) (/Δ403-459) closely recapitulates the human PHA2E phenotype. These mice also show changes in the arterial pulse waveform, suggesting a vascular contribution to their hypertension not reported in previous FHHt models. These findings may explain the severity of the FHHt phenotype caused by CUL3 mutations compared to those reported in KLHL3 or WNK kinases.
Assuntos
Proteínas Culina/genética , Modelos Animais de Doenças , Mutação , Pseudo-Hipoaldosteronismo/genética , Animais , Proteínas Culina/metabolismo , Células HEK293 , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos , Camundongos Knockout , Proteínas Serina-Treonina Quinases/metabolismo , Pseudo-Hipoaldosteronismo/metabolismo , Pseudo-Hipoaldosteronismo/fisiopatologiaRESUMO
OBJECTIVE: The aim of this study was to investigate the role of pravastatin, as an adjunctive therapy, on inflammatory markers, lipid and glucose metabolism, psychopathology, and cognition in subjects with schizophrenia and schizoaffective disorder. METHODS: Schizophrenia or schizoaffective subjects (N=60) were randomized to receive either a 12-week supply of pravastatin 40 mg/day or placebo treatment. Anthropometric measures, lipids and glucose metabolism, inflammatory markers, psychopathology and cognitive performance were assessed at baseline, 6 weeks and 12 weeks. RESULTS: Pravastatin use was associated with a significant decrease in total cholesterol, low density lipoprotein (LDL) cholesterol and LDL particle number levels, but was not associated with any significant changes in cognition or psychopathology in the participants, except a significant decrease in the Positive and Negative Syndrome Scale (PANSS) positive symptom score from baseline to week 6. However, this decrease failed to remain significant at 12 weeks. Interestingly, triglycerides, LDL-cholesterol, total cholesterol, LDL particle number, small LDL particle number, large very low density lipoprotein (VLDL) particle number and C-reactive protein (CRP) followed a similar pattern at 6 and 12 weeks as psychopathology. CONCLUSIONS: These results suggest that a randomized trial with a larger sample size and a higher dosage of pravastatin would be helpful in further evaluating the anti-inflammatory properties of pravastatin, its association with improvements in cognitive symptoms, and its potential to reduce positive and negative symptoms associated with schizophrenia or schizoaffective disorders.
Assuntos
Anticolesterolemiantes/farmacologia , Pravastatina/farmacologia , Transtornos Psicóticos/tratamento farmacológico , Esquizofrenia/tratamento farmacológico , Adulto , Anticolesterolemiantes/administração & dosagem , Transtornos Cognitivos/tratamento farmacológico , Sinergismo Farmacológico , Feminino , Humanos , Inflamação/tratamento farmacológico , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Pravastatina/administração & dosagem , Transtornos Psicóticos/imunologia , Transtornos Psicóticos/metabolismo , Transtornos Psicóticos/fisiopatologia , Esquizofrenia/imunologia , Esquizofrenia/metabolismo , Esquizofrenia/fisiopatologia , Resultado do TratamentoRESUMO
PURPOSE: We examined the feasibility and outcome of electromyographically triggered electrical muscle stimulation (EMG-ES) plus unilateral or bilateral task specific practice on arm function in chronic stroke survivors with moderate-severe hemiplegia. Transcranial magnetic stimulation was used to examine inter-hemispheric inhibition (IHI) acting on the stroke-affected hemisphere in a subset of eight participants. METHODS: Twenty-one stroke survivors (14 males; mean time post stroke 57.9 months) participated in this pilot investigation. Participants underwent a six-week program of daily EMG-ES training with random assignment to concurrent task practice using the stroke-affected hand only or both hands. The upper-extremity subscale of the Fugl-Meyer (FMUE) and the Arm Motor Ability Test (AMAT) were completed at baseline, 0-, 1-, and 3-months post-intervention. RESULTS: Following the intervention, FMUE (F(3, 57) = 3.89, p = .01, ηp2 = .17) and AMAT (F(3, 57) = 12.6, p = .01, ηp2 = .39) scores improved, and remained better than baseline at three months re-assessment. The difference between groups was not significant. A non-significant decrease in IHI was observed post-intervention. CONCLUSIONS: An intensive program of EMG-ES assisted functional training is feasible, well tolerated, and leads to improvements in moderate-severe deficits of arm function post stroke. Larger placebo controlled studies are needed to explore any advantage of bilateral over unilateral EMG-ES assisted training.