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1.
Cardiol Young ; : 1-7, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38622972

RESUMO

BACKGROUND: The study of psychological well-being and related resilient outcomes is of increasing focus in cardiovascular research. Despite the critical importance of psychological well-being and related resilient outcomes in promoting optimal cardiac health, there have been very few psychological interventions directed towards children with heart disease. This paper describes the development and theoretical framework of the WE BEAT Wellbeing Education Program, a group-based psychoeducation and coping skills training intervention designed to improve psychological well-being and resilience in adolescents with paediatric heart disease. METHODS: Program development was informed by patient and family needs and input gathered via large, international survey methods as well as qualitative investigation, a theoretical framework, and related resilience intervention research. RESULTS: An overview of the WE BEAT intervention components and structure of the programme is provided. CONCLUSIONS: The WE BEAT Wellbeing Education Program was developed as one of the first resiliency-focused interventions in paediatric heart disease with an overall objective to foster positive psychological well-being and resilient outcomes through a health promotion and prevention lens in an accessible format while providing access to safe, peer-to-peer community building. Feasibility pilot results are forthcoming. Future directions include mobile app-based delivery and larger-scale efficacy and implementation trials.

2.
Mol Ther ; 30(8): 2722-2745, 2022 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-35524407

RESUMO

Second-order spinal cord excitatory neurons play a key role in spinal processing and transmission of pain signals to the brain. Exogenously induced change in developmentally imprinted excitatory neurotransmitter phenotypes of these neurons to inhibitory has not yet been achieved. Here, we use a subpial dorsal horn-targeted delivery of AAV (adeno-associated virus) vector(s) encoding GABA (gamma-aminobutyric acid) synthesizing-releasing inhibitory machinery in mice with neuropathic pain. Treated animals showed a progressive and complete reversal of neuropathic pain (tactile and brush-evoked pain behavior) that persisted for a minimum of 2.5 months post-treatment. The mechanism of this treatment effect results from the switch of excitatory to preferential inhibitory neurotransmitter phenotype in dorsal horn nociceptive neurons and a resulting increase in inhibitory activity in regional spinal circuitry after peripheral nociceptive stimulation. No detectable side effects (e.g., sedation, motor weakness, loss of normal sensation) were seen between 2 and 13 months post-treatment in naive adult mice, pigs, and non-human primates. The use of this treatment approach may represent a potent and safe treatment modality in patients suffering from spinal cord or peripheral nerve injury-induced neuropathic pain.


Assuntos
Neuralgia , Nociceptores , Animais , Técnicas de Transferência de Genes , Camundongos , Neuralgia/etiologia , Neuralgia/terapia , Células do Corno Posterior , Medula Espinal , Corno Dorsal da Medula Espinal , Suínos
3.
J Interv Cardiol ; 2022: 7602793, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36447937

RESUMO

Background: Fontan-associated liver disease is a well-known sequela following the Fontan procedure for patients living with single-ventricle heart disease. Pulmonary vasodilators, such as phosphodiesterase type 5 inhibitors, have emerged as a potential therapeutic option for lowering central venous pressures by reducing pulmonary vascular resistance. Method: We performed a single-center retrospective review of Fontan patients who were placed on pulmonary vasodilator therapy with prehemodynamic and posthemodynamic, MR elastography, and histologic assessments. Results: A total of 125 patients with Fontan circulation underwent surveillance with cardiac catheterization during the review period. Fifty-three (42%) patients who did not have increased end-diastolic pressures at the time of cardiac catheterization were started on phosphodiesterase type 5 inhibitor therapy. Nine patients (17%) underwent posttherapy follow-up catheterization. The mean Fontan pressure decreased from 15.4 ± 3.3 mmHg to 13.3 ± 2.5 mmHg (p=0.026), after initiation of pulmonary vasodilatory therapy. There was no change in end-diastolic pressure, transpulmonary gradient, wedge pressure, pulmonary vascular resistance, cardiac index, or saturation. Eleven patients (21%) underwent pretherapy MR elastography testing with posttherapy follow-up MR elastography. We found no improvement in liver stiffness score following the application of pulmonary vasodilators. Three patients underwent pretherapy and posttherapy liver biopsies, with variable histological changes observed within the hepatic parenchyma. Conclusions: These data demonstrate indeterminate results for the selective use of pulmonary vasodilators but highlight the need for large prospective randomized control trials of pulmonary vasodilator therapies to fully assess the benefit of such therapies in Fontan-associated liver disease.


Assuntos
Cateterismo Cardíaco , Vasodilatadores , Humanos , Vasodilatadores/uso terapêutico , Estudos Prospectivos , Biópsia , Fígado
4.
Cardiol Young ; 32(4): 668-670, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34486517

RESUMO

A 4-hour-old infant with profound cyanosis on an alprostadil infusion was urgently transferred to Rady Children's Hospital with suspected CHD. Upon arrival, urgent echocardiography was performed but could not confirm the presence of discrete pulmonary veins or pulmonary venous drainage. Given the difficulty in delineating the anatomy, a cardiac CT scan was performed and demonstrated a nearly atretic common pulmonary vein with multiple small collaterals that drained to systemic veins. Due to the high risk of mortality associated with operative repair, the decision was made to proceed with compassionate withdrawal of care. The described anatomy of common pulmonary vein atresia remains rare, and to our knowledge, fewer than 40 cases have been reported in the literature. Albeit rare, common pulmonary vein atresia should be considered in the differential diagnosis of a severely cyanotic neonate.


Assuntos
Cardiopatias Congênitas , Veias Pulmonares , Malformações Vasculares , Criança , Cianose/complicações , Ecocardiografia , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/diagnóstico por imagem , Humanos , Lactente , Recém-Nascido , Veias Pulmonares/anormalidades , Malformações Vasculares/complicações
5.
Genes Dev ; 26(12): 1312-25, 2012 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-22677548

RESUMO

Owing to their covalent modification by cholesterol and palmitate, Hedgehog (Hh) signaling proteins are localized predominantly to the plasma membrane of expressing cells. Yet Hh proteins are also capable of mobilizing to and eliciting direct responses from distant cells. The zebrafish you gene, identified genetically >15 years ago, was more recently shown to encode a secreted glycoprotein that acts cell-nonautonomously in the Hh signaling pathway by an unknown mechanism. We investigated the function of the protein encoded by murine Scube2, an ortholog of you, and found that it mediates release in soluble form of the mature, cholesterol- and palmitate-modified Sonic hedgehog protein signal (ShhNp) when added to cultured cells or purified detergent-resistant membrane microdomains containing ShhNp. The efficiency of Scube2-mediated release of ShhNp is enhanced by the palmitate adduct of ShhNp and by coexpression in ShhNp-producing cells of mDispatchedA (mDispA), a transporter-like protein with a previously defined role in the release of lipid-modified Hh signals. The structural determinants of Scube2 required for its activity in cultured cell assays match those required for rescue of you mutant zebrafish embryos, and we thus conclude that the role of Scube/You proteins in Hh signaling in vivo is to facilitate the release and mobilization of Hh proteins for distant action.


Assuntos
Proteínas Hedgehog/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Metabolismo dos Lipídeos , Transdução de Sinais , Proteínas Adaptadoras de Transdução de Sinal , Animais , Proteínas de Ligação ao Cálcio , Sistema Livre de Células , Células Cultivadas , Colesterol/metabolismo , Meios de Cultura/farmacologia , Detergentes/farmacologia , Células HEK293 , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/química , Metabolismo dos Lipídeos/efeitos dos fármacos , Microdomínios da Membrana/efeitos dos fármacos , Microdomínios da Membrana/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Palmitatos/farmacologia , Ligação Proteica/efeitos dos fármacos , Estabilidade Proteica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Solubilidade/efeitos dos fármacos , Relação Estrutura-Atividade , Peixe-Zebra
6.
J Appl Meas ; 20(2): 154-166, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31120433

RESUMO

This simulation study explores the effects of missing data mechanisms, proportions of missing data, sample size, and test length on the biases and standard errors of item parameters using the Rasch measurement model. When responses were missing completely at random (MCAR) or missing at random (MAR), item parameters were unbiased. When responses were missing not at random (MNAR), item parameters were severely biased, especially when the proportion of missing responses was high. Standard errors were primarily affected by sample size, with larger samples associated with smaller standard errors. Standard errors were inflated in MCAR and MAR conditions, while MNAR standard errors were similar to what they would have been, had the data been complete. This paper supports the conclusion that the Rasch model can handle varying amounts of missing data, provided that the missing responses are not MNAR.


Assuntos
Interpretação Estatística de Dados , Modelos Estatísticos , Viés , Psicometria , Tamanho da Amostra
7.
J Appl Meas ; 20(1): 1-12, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30789829

RESUMO

This paper investigates a strategy for accounting for correct guessing with the Rasch model that we entitled the Guessing Adjustment. This strategy involves the identification of all person/item encounters where the probability of a correct response is below a specified threshold. These responses are converted to missing data and the calibration is conducted a second time. This simulation study focuses on the effects of different probability thresholds across varying conditions of sample size, amount of correct guessing, and item difficulty. Biases, standard errors, and root mean squared errors were calculated within each condition. Larger probability thresholds were generally associated with reductions in bias and increases in standard errors. Across most conditions, the reduction in bias was more impactful than the decrease in precision, as reflected by the RMSE. The Guessing Adjustment is an effective means for reducing the impact of correct guessing and the choice of probability threshold matters.


Assuntos
Modelos Estatísticos , Viés , Probabilidade , Psicometria , Tamanho da Amostra
8.
J Neurosci Res ; 96(4): 688-695, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28543565

RESUMO

Carbohydrate fuel augmentation following traumatic brain injury may be a viable treatment to improve recovery when cerebral oxidative metabolism of glucose is depressed. We performed a primed constant sodium L-lactate infusion in 11 moderate to severely brain injured adults. Blood was collected before and periodically during the infusion study. We quantified global cerebral uptake of glucose and lactate and other systemic metabolites associated with energy metabolism. Our hypothesis was that cerebral lactate uptake, as measured by the arteriovenous difference of lactate (AVDlac), would increase in severely injured TBI patients in the neurocritical care unit. Infusion of sodium L-lactate changed net cerebral lactate release, where the arteriovenous difference of lactate is negative, to net cerebral lactate uptake. Results from a mixed effects model of AVDlac with the fixed effects of infusion time, arterial lactate concentration, arterial glucose concentration and arteriovenous difference of glucose shows that doubling arterial lactate concentration (from .92 to 1.84 mM) results in an increase in AVDlac from -.078 mM to .090 mM. We did not detect changes in systemic glucose during the course of the infusion study and observed significant changes in alanine (30% [20 39]), glutamine (34% [24 43]), acetate (87% [60 113]), valine (40% [28 51]), and leucine (24% [16 32]) from baseline levels. Further studies are required to establish the impact of lactate supplementation on cerebral and systemic flux of lactate, on gluconeogenesis, and on the impact on cerebral energetics following injury. © 2017 Wiley Periodicals, Inc.


Assuntos
Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/metabolismo , Ácido Láctico/metabolismo , Lactato de Sódio/uso terapêutico , Adulto , Idoso , Glicemia/metabolismo , Encéfalo/metabolismo , Metabolismo Energético/efeitos dos fármacos , Feminino , Humanos , Infusões Intravenosas , Ácido Láctico/sangue , Masculino , Pessoa de Meia-Idade , Lactato de Sódio/administração & dosagem
9.
J Neurosci Res ; 96(4): 696-701, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28609544

RESUMO

Traumatic brain injury (TBI) is associated with acute cerebral metabolic crisis (ACMC). ACMC-related atrophy appears to be prominent in frontal and temporal lobes following moderate-to-severe TBI. This atrophy is correlated with poorer cognitive outcomes in TBI. The current study investigated ability of acute glucose and lactate metabolism to predict long-term recovery of frontal-temporal cognitive function in participants with moderate-to-severe TBI. Cerebral metabolic rate of glucose and lactate were measured by the Kety-Schmidt method on days 0-7 post-injury. Indices of frontal-temporal cognitive processing were calculated for six months post-injury; 12 months post-injury; and recovery (the difference between the six- and 12-month scores). Glucose and lactate metabolism were included in separate regression models, as they were highly intercorrelated. Also, glucose and lactate values were centered and averaged and included in a final regression model. Models for the prediction frontal-temporal cognition at six and 12 months post-injury were not significant. However, average glucose and lactate metabolism predicted recovery of frontal-temporal cognition, accounting for 23% and 22% of the variance, respectively. Also, maximum glucose metabolism, but not maximum lactate metabolism, was an inverse predictor in the recovery of frontal-temporal cognition, accounting for 23% of the variance. Finally, the average of glucose and lactate metabolism predicted frontal-temporal cognitive recovery, accounting for 22% of the variance. These data indicate that acute glucose and lactate metabolism both support cognitive recovery from TBI. Also, our data suggest that control of endogenous fuels and/or supplementation with exogenous fuels may have therapeutic potential for cognitive recovery from TBI.


Assuntos
Lesões Encefálicas Traumáticas/metabolismo , Cognição/fisiologia , Glucose/metabolismo , Ácido Láctico/metabolismo , Adulto , Lesões Encefálicas Traumáticas/complicações , Metabolismo Energético , Lobo Frontal , Escala de Coma de Glasgow , Humanos , Testes Neuropsicológicos , Lobo Temporal
10.
Ecology ; 98(1): 211-227, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28052396

RESUMO

Understanding the genecology of forest trees is critical for gene conservation, for predicting the effects of climate change and climate change adaptation, and for successful reforestation. Although common genecological patterns have emerged, species-specific details are also important. Which species are most vulnerable to climate change? Which are the most important adaptive traits and environmental drivers of natural selection? Even though species have been classified as adaptive specialists vs. adaptive generalists, large-scale studies comparing different species in the same experiment are rare. We studied the genecology of Norway spruce (Picea abies) and silver fir (Abies alba), two co-occurring but ecologically distinct European conifers in Central Europe. For each species, we collected seed from more than 90 populations across Switzerland, established a seedling common-garden test, and developed genecological models that associate population variation in seedling growth and phenology to climate, soil properties, and site water balance. Population differentiation and associations between seedling traits and environmental variables were much stronger for Norway spruce than for silver fir, and stronger for seedling height growth than for bud phenology. In Norway spruce, height growth and second flushing were strongly associated with temperature and elevation, with seedlings from the lowlands being taller and more prone to second flush than seedlings from the Alps. In silver fir, height growth was more weakly associated with temperature and elevation, but also associated with water availability. Soil characteristics explained little population variation in both species. We conclude that Norway spruce has become an adaptive specialist because trade-offs between rapid juvenile growth and frost avoidance have subjected it to strong diversifying natural selection based on temperature. In contrast, because silver fir has a more conservative growth habit, it has evolved to become an adaptive generalist. This study demonstrates that co-occurring tree species can develop very different adaptive strategies under identical environmental conditions, and suggests that Norway spruce might be more vulnerable to future maladaptation due to rapid climate change than silver fir.


Assuntos
Abies/genética , Picea/genética , Plântula/genética , Suíça , Árvores
11.
Neurocrit Care ; 26(2): 239-246, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27761730

RESUMO

BACKGROUND: The objective was to investigate the impact of targeting tight glycemic control (4.4-6.1 mM) on endogenous ketogenesis in severely head-injured adults. METHODS: The data were prospectively collected during a randomized, within-patient crossover study comparing tight to loose glycemic control, defined as 6.7-8.3 mM. Blood was collected periodically during both tight and loose glycemic control epochs. Post hoc analysis of insulin dose and total nutritional provision was performed. RESULTS: Fifteen patients completed the crossover study. Total ketones were increased 81 µM ([38 135], p < 0.001) when blood glucose was targeted to tight (4.4-6.1 mM) compared with loose glycemic control (6.7-8.3 mM), corresponding to a 60 % increase. There was a significant decrease in total nutritional provisions (p = 0.006) and a significant increase in insulin dose (p = 0.008). CONCLUSIONS: Permissive underfeeding was tolerated when targeting tight glycemic control, but total nutritional support is an important factor when treating hyperglycemia.


Assuntos
Glicemia/análise , Lesões Encefálicas Traumáticas/sangue , Lesões Encefálicas Traumáticas/terapia , Hiperglicemia/sangue , Hiperglicemia/terapia , Corpos Cetônicos/sangue , Avaliação de Resultados em Cuidados de Saúde , Adulto , Estudos Cross-Over , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
12.
Development ; 140(15): 3167-75, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23804499

RESUMO

In peripheral nerves, Schwann cells form the myelin sheath, which allows the efficient propagation of action potentials along axons. The transcription factor Krox20 regulates the initiation of myelination in Schwann cells and is also required to maintain mature myelin. The adhesion G protein-coupled receptor (GPCR) Gpr126 is essential for Schwann cells to initiate myelination, but previous studies have not addressed the role of Gpr126 signaling in myelin maturation and maintenance. Through analysis of Gpr126 in zebrafish, we define two distinct mechanisms controlling the initiation and maturation of myelin. We show that gpr126 mutant Schwann cells elaborate mature myelin sheaths and maintain krox20 expression for months, provided that the early signaling defect is bypassed by transient elevation of cAMP. At the onset of myelination, Gpr126 and protein kinase A (PKA) function as a switch that allows Schwann cells to initiate krox20 expression and myelination. After myelination is initiated, krox20 expression is maintained and myelin maturation proceeds independently of Gpr126 signaling. Transgenic analysis indicates that the Krox20 cis-regulatory myelinating Schwann cell element (MSE) becomes active at the onset of myelination and that this activity is dependent on Gpr126 signaling. Activity of the MSE declines after initiation, suggesting that other elements are responsible for maintaining krox20 expression in mature nerves. We also show that elevated cAMP does not initiate myelination in the absence of functional Neuregulin 1 (Nrg1) signaling. These results indicate that the mechanisms regulating the initiation of myelination are distinct from those mediating the maturation and maintenance of myelin.


Assuntos
Bainha de Mielina/fisiologia , Receptores Acoplados a Proteínas G/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/embriologia , Peixe-Zebra/fisiologia , Animais , Animais Geneticamente Modificados , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Proteína 2 de Resposta de Crescimento Precoce/genética , Proteína 2 de Resposta de Crescimento Precoce/metabolismo , Expressão Gênica , Genes erbB-2 , Sistema da Linha Lateral/embriologia , Sistema da Linha Lateral/fisiologia , Mutação , Proteína Básica da Mielina/genética , Proteína Básica da Mielina/metabolismo , Bainha de Mielina/ultraestrutura , Neuregulina-1/genética , Neuregulina-1/metabolismo , Receptores Acoplados a Proteínas G/genética , Células de Schwann/fisiologia , Células de Schwann/ultraestrutura , Transdução de Sinais , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética
13.
Plant Biotechnol J ; 14(4): 1095-8, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26360509

RESUMO

Agriculture is now facing the 'perfect storm' of climate change, increasing costs of fertilizer and rising food demands from a larger and wealthier human population. These factors point to a global food deficit unless the efficiency and resilience of crop production is increased. The intensification of agriculture has focused on improving production under optimized conditions, with significant agronomic inputs. Furthermore, the intensive cultivation of a limited number of crops has drastically narrowed the number of plant species humans rely on. A new agricultural paradigm is required, reducing dependence on high inputs and increasing crop diversity, yield stability and environmental resilience. Genomics offers unprecedented opportunities to increase crop yield, quality and stability of production through advanced breeding strategies, enhancing the resilience of major crops to climate variability, and increasing the productivity and range of minor crops to diversify the food supply. Here we review the state of the art of genomic-assisted breeding for the most important staples that feed the world, and how to use and adapt such genomic tools to accelerate development of both major and minor crops with desired traits that enhance adaptation to, or mitigate the effects of climate change.


Assuntos
Produtos Agrícolas/genética , Abastecimento de Alimentos/métodos , Genômica/métodos , Melhoramento Vegetal/métodos , Mudança Climática , Variação Genética
14.
Sleep Breath ; 20(1): 271-6, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26527205

RESUMO

PURPOSE: To evaluate correlations between serotonin transporter (SERT) uptake ability in human peripheral platelets and sleep bruxism (SB) frequency. METHODS: Subjects were consecutively recruited from sixth-year students at Okayama University Dental School. Subjects were excluded if they (1) were receiving orthodontic treatment, (2) had a dermatological disease, (3) had taken an antidepressant within 6 months, or (4) had used an oral appliance within 6 months. SB frequency was determined as the summary score of three consecutive night assessments using a self-contained electromyography detector/analyzer in their home. Fasting peripheral venous blood samples were collected in the morning following the final SB assessment. SERT amount and platelet number were quantified via an ELISA assay and flow cytometry, respectively. Functional SERT characterization, 5-hydroxytryptamine (5-HT) uptake, maximum velocity (V max), and an affinity constant (K m ) were assessed with a [(3)H] 5-HT uptake assay. The correlations between these variables and SB level were evaluated. RESULTS: Among 50 eligible subjects (26 males, mean age 25.4 ± 2.41 years), 7 were excluded because of venipuncture failure, smoking, and alcohol intake during the experimental period. A small but significant negative correlation between SB level and [(3)H] 5-HT uptake was observed (Spearman's correlation R (2) = 0.063, p = 0.04). However, there were no significant correlations between SB level and total platelet amount, SERT, V max, and K m values (p = 0.08, 0.12, 0.71, and 0.68, respectively). CONCLUSIONS: Platelet serotonin uptake is significantly associated with SB frequency, yet only explains a small amount of SB variability.


Assuntos
Plaquetas/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/sangue , Bruxismo do Sono/sangue , Bruxismo do Sono/epidemiologia , Adulto , Eletromiografia , Feminino , Humanos , Masculino , Contagem de Plaquetas , Polissonografia , Serotonina/sangue , Estatística como Assunto , Adulto Jovem
15.
J Neurosci ; 34(44): 14717-32, 2014 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-25355224

RESUMO

Mutations in Kinesin proteins (Kifs) are linked to various neurological diseases, but the specific and redundant functions of the vertebrate Kifs are incompletely understood. For example, Kif5A, but not other Kinesin-1 heavy-chain family members, is implicated in Charcot-Marie-Tooth disease (CMT) and Hereditary Spastic Paraplegia (HSP), but the mechanism of its involvement in the progressive axonal degeneration characteristic of these diseases is not well understood. We report that zebrafish kif5Aa mutants exhibit hyperexcitability, peripheral polyneuropathy, and axonal degeneration reminiscent of CMT and HSP. Strikingly, although kif5 genes are thought to act largely redundantly in other contexts, and zebrafish peripheral neurons express five kif5 genes, kif5Aa mutant peripheral sensory axons lack mitochondria and degenerate. We show that this Kif5Aa-specific function is cell autonomous and is mediated by its C-terminal tail, as only Kif5Aa and chimeric motors containing the Kif5Aa C-tail can rescue deficits. Finally, concurrent loss of the kinesin-3, kif1b, or its adaptor kbp, exacerbates axonal degeneration via a nonmitochondrial cargo common to Kif5Aa. Our results shed light on Kinesin complexity and reveal determinants of specific Kif5A functions in mitochondrial transport, adaptor binding, and axonal maintenance.


Assuntos
Axônios/metabolismo , Cinesinas/metabolismo , Mitocôndrias/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Animais , Transporte Axonal/fisiologia , Cinesinas/genética , Mitocôndrias/genética , Degeneração Neural/genética , Degeneração Neural/metabolismo , Peixe-Zebra , Proteínas de Peixe-Zebra/genética
16.
Brain Inj ; 29(2): 139-53, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25587743

RESUMO

PRIMARY OBJECTIVE: The aim of this literature review was to systematically describe the sequential metabolic changes that occur following concussive injury, as well as identify and characterize the major concepts associated with the neurochemical cascade. RESEARCH DESIGN: Narrative literature review. CONCLUSIONS: Concussive injury initiates a complex cascade of pathophysiological changes that include hyper-acute ionic flux, indiscriminant excitatory neurotransmitter release, acute hyperglycolysis and sub-acute metabolic depression. Additionally, these metabolic changes can subsequently lead to impaired neurotransmission, alternate fuel usage and modifications in synaptic plasticity and protein expression. The combination of these metabolic alterations has been proposed to cause the transient and prolonged neurological deficits that typically characterize concussion. Consequently, understanding the implications of the neurochemical cascade may lead to treatment and return-to-play guidelines that can minimize the chronic effects of concussive injury.


Assuntos
Traumatismos em Atletas/metabolismo , Concussão Encefálica/metabolismo , Cálcio/metabolismo , Neurotransmissores/metabolismo , Traumatismos em Atletas/fisiopatologia , Biomarcadores/metabolismo , Concussão Encefálica/fisiopatologia , Glicólise , Humanos , Recuperação de Função Fisiológica
17.
Acta Neurochir Suppl ; 118: 115-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23564115

RESUMO

Proton nuclear magnetic resonance (H-NMR) spectroscopic analysis of cerebral spinal fluid provides a quick, non-invasive modality for evaluating the metabolic activity of brain-injured patients. In a prospective study, we compared the CSF of 44 TBI patients and 13 non-injured control subjects. CSF was screened for ten parameters: ß-glucose (Glu), lactate (Lac), propylene glycol (PG), glutamine (Gln), alanine (Ala), α-glucose (A-Glu), pyruvate (PYR), creatine (Cr), creatinine (Crt), and acetate (Ace). Using mixed effects measures, we discovered statistically significant differences between control and trauma concentrations (mM). TBI patients had significantly higher concentrations of PG, while statistical trends existed for lactate, glutamine, and creatine. TBI patients had a significantly decreased concentration of total creatinine. There were no significant differences between TBI patients and non-injured controls regarding ß- or α-glucose, alanine, pyruvate or acetate. Correlational analysis between metabolites revealed that the strongest significant correlations in non-injured subjects were between ß- and α-glucose (r = 0.74), creatinine and pyruvate (r = 0.74), alanine and creatine (r = 0.62), and glutamine and α-glucose (r = 0.60). For TBI patients, the strongest significant correlations were between lactate and α-glucose (r = 0.54), lactate and alanine (r = 0.53), and α-glucose and alanine (r = 0.48). The GLM and multimodel inference indicated that the combined metabolites of PG, glutamine, α-glucose, and creatinine were the strongest predictors for CMRO2, ICP, and GOSe. By analyzing the CSF of patients with TBI, our goal was to create a metabolomic fingerprint for brain injury.


Assuntos
Aminoácidos/líquido cefalorraquidiano , Lesões Encefálicas/líquido cefalorraquidiano , Propilenoglicol/líquido cefalorraquidiano , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Feminino , Glucose/líquido cefalorraquidiano , Humanos , Pressão Intracraniana , Espectroscopia de Ressonância Magnética , Masculino , Metabolômica , Pessoa de Meia-Idade , Prótons , Adulto Jovem
18.
J Am Heart Assoc ; 12(21): e029847, 2023 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-37889178

RESUMO

Background Congenital heart disease (CHD) is a life-long disease with long-term consequences on physical and mental health. Patients with CHD face multifaceted physical and psychosocial challenges. Resilience is an important factor that can be protective and positively impact mental health. We studied resiliency and its associated factors in teenagers and young adults with and without CHD using a social media-delivered survey. Resilience was measured using the 25-item Connor-Davidson Resilience Scale, a validated metric with a historical mean of 80.4/100 in the general adult population. Methods and Results Individuals with and without CHD, aged 10 to 25 years, were prospectively recruited on social media to complete an online survey. The survey was completed from January to February 2022. Respondents provided information on their demographics and CHD details (where applicable) and completed the Connor-Davidson Resilience Scale. As a group, participants with CHD had higher resilience scores compared with same-aged healthy individuals (65.3±16.1 versus 55.4±13.8; P<0.001). For both cohorts, sex, race, and age were not associated with differences in resilience score. For individuals with CHD, lower resilience was associated with more hospital admissions, lack of exercise, presence of a mental health diagnosis, and no participation in support groups or disease-specific camps. Conclusions Young people with CHD had higher resilience than individuals without CHD in our sample. We identified several factors, both modifiable and nonmodifiable, that are associated with higher resilience. Awareness of resiliency and its contributors in the population with CHD may assist medical teams in improving patient physical and psychological well-being.


Assuntos
Cardiopatias Congênitas , Saúde Mental , Adulto Jovem , Adolescente , Humanos , Cardiopatias Congênitas/psicologia
19.
Cell Transplant ; 32: 9636897221107009, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37088987

RESUMO

One of the challenges in clinical translation of cell-replacement therapies is the definition of optimal cell generation and storage/recovery protocols which would permit a rapid preparation of cell-treatment products for patient administration. Besides, the availability of injection devices that are simple to use is critical for potential future dissemination of any spinally targeted cell-replacement therapy into general medical practice. Here, we compared the engraftment properties of established human-induced pluripotent stem cells (hiPSCs)-derived neural precursor cell (NPCs) line once cells were harvested fresh from the cell culture or previously frozen and then grafted into striata or spinal cord of the immunodeficient rat. A newly developed human spinal injection device equipped with a spinal cord pulsation-cancelation magnetic needle was also tested for its safety in an adult immunosuppressed pig. Previously frozen NPCs showed similar post-grafting survival and differentiation profile as was seen for freshly harvested cells. Testing of human injection device showed acceptable safety with no detectable surgical procedure or spinal NPCs injection-related side effects.


Assuntos
Reprogramação Celular , Células-Tronco Pluripotentes Induzidas , Injeções Espinhais , Células-Tronco Neurais , Transplante de Células-Tronco , Adulto , Animais , Humanos , Ratos , Diferenciação Celular/fisiologia , Reprogramação Celular/genética , Reprogramação Celular/fisiologia , Vetores Genéticos/genética , Sobrevivência de Enxerto/fisiologia , Células-Tronco Pluripotentes Induzidas/fisiologia , Células-Tronco Pluripotentes Induzidas/transplante , Injeções Espinhais/efeitos adversos , Injeções Espinhais/instrumentação , Injeções Espinhais/métodos , Células-Tronco Neurais/fisiologia , Células-Tronco Neurais/transplante , Vírus Sendai , Manejo de Espécimes/métodos , Transplante de Células-Tronco/efeitos adversos , Transplante de Células-Tronco/instrumentação , Transplante de Células-Tronco/métodos , Suínos , Coleta de Tecidos e Órgãos/métodos , Resultado do Tratamento , Encéfalo , Medula Espinal
20.
Crit Care Med ; 40(6): 1923-9, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22610193

RESUMO

OBJECTIVE: To determine the effects of tight glycemic control on brain metabolism after traumatic brain injury using brain positron emission tomography and microdialysis. DESIGN: Single-center, randomized controlled within-subject crossover observational trial. SETTING: Academic intensive care unit. METHODS: We performed a prospective, unblinded randomized controlled within-subject crossover trial of tight (80-110 mg/dL) vs. loose (120-150 mg/dL) glycemic control in patients with severe traumatic brain injury to determine the effects of glycemic control on brain glucose metabolism, as measured by [18F] deoxy-D-glucose brain positron emission tomography. Brain microdialysis was done simultaneously. MEASUREMENTS AND MAIN RESULTS: Thirteen severely injured traumatic brain injury patients underwent the study between 3 and 8 days (mean 4.8 days) after traumatic brain injury. In ten of these subjects, global brain and gray matter tissues demonstrated higher glucose metabolic rates while glucose was under tight control as compared with loose control (3.2 ± 0.6 vs. 2.4 + 0.4, p = .02 [whole brain] and 3.8 ± 1.4 vs. 2.9 ± 0.8, p = .05 [gray matter]). However, the responses were heterogeneous with pericontusional tissue demonstrating the least state-dependent change. Cerebral microdialysis demonstrated more frequent critical reductions in glucose (p = .02) and elevations of lactate/pyruvate ratio (p = .03) during tight glycemic control. CONCLUSION: Tight glycemic control results in increased global glucose uptake and an increased cerebral metabolic crisis after traumatic brain injury. The mechanisms leading to the enhancement of metabolic crisis are unclear, but delivery of more glucose through mild hyperglycemia may be necessary after traumatic brain injury.


Assuntos
Lesões Encefálicas/metabolismo , Encéfalo/metabolismo , Glucose/metabolismo , Estresse Fisiológico/fisiologia , Adolescente , Adulto , Idoso , Lesões Encefálicas/diagnóstico por imagem , Lesões Encefálicas/fisiopatologia , Estudos Cross-Over , Feminino , Fluordesoxiglucose F18/farmacocinética , Humanos , Masculino , Microdiálise , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Estudos Prospectivos , Compostos Radiofarmacêuticos/farmacocinética , Índices de Gravidade do Trauma , Adulto Jovem
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