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BACKGROUND: It is still unknown whether the mechanisms proposed by the Reserve Capacity Model (RCM) explaining socio-economic health and wellbeing inequities in high income countries can be applied to low-income countries. This study investigates whether different reserve capacities (intra-, inter-personal, and tangible) can explain the association between relative socio-economic position (SEP) and wellbeing outcome measures among Ethiopian women working in Foreign Direct Investment (FDI). METHOD: Using a cross-sectional design, we collected quantitative survey data among 2,515 women working in the apparel and floriculture sectors in Ethiopia, measuring GHQ-12 mental health problems, multi-dimensional wellbeing, relative SEP, psychological capital (PsyCap), social support (emotional and financial social support network), and tangible assets (e.g., owning mobile phone, having access to toilet facilities). We used cluster-adjusted structural equation modelling to test whether PsyCap, social support, and/or tangible assets mediate the association between relative SEP (IV) and GHQ-12 mental health problems and multi-dimensional wellbeing (DVs). RESULTS: PsyCap and the size of the financial support network significantly mediate the socio-economic gradient in both wellbeing outcomes. The size of the emotional social support network shows no association with multi-dimensional wellbeing and shows an unexpected negative association with GHQ-12 mental health problems scores, including a significant mediation effect. Tangible assets show no association with the wellbeing outcome measures and do not mediate socio-economic mental health problems and wellbeing inequities. CONCLUSIONS: The RCM can be applied in low-income countries, although in unexpected ways. Similar to findings from high-income countries, PsyCap and size of the financial social support network show significant mediation effects in explaining mental health problems and wellbeing inequities in Ethiopia. These reserves could therefore serve as a buffer for socio-economic inequities in mental health and wellbeing and can therefore assist in decreasing these inequities for women working in FDI sectors in Ethiopia.
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Transtornos Mentais , Apoio Social , Humanos , Feminino , Adulto , Estudos Transversais , Etiópia , Transtornos Mentais/psicologia , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Fatores Socioeconômicos , Adulto Jovem , Disparidades nos Níveis de Saúde , Saúde Mental/estatística & dados numéricos , Inquéritos e QuestionáriosRESUMO
Mitochondrial DNA (mtDNA) haplotype regulates mitochondrial structure/function and reactive oxygen species in aortocaval fistula (ACF) in mice. Here, we unravel the mitochondrial haplotype effects on cardiomyocyte mitochondrial ultrastructure and transcriptome response to ACF in vivo. Phenotypic responses and quantitative transmission electron microscopy (TEM) and RNA sequence at 3 days were determined after sham surgery or ACF in vivo in cardiomyocytes from wild-type (WT) C57BL/6J (C57n:C57mt) and C3H/HeN (C3Hn:C3Hmt) and mitochondrial nuclear exchange mice (C57n:C3Hmt or C3Hn:C57mt). Quantitative TEM of cardiomyocyte mitochondria C3HWT hearts have more electron-dense compact mitochondrial cristae compared with C57WT. In response to ACF, mitochondrial area and cristae integrity are normal in C3HWT; however, there is mitochondrial swelling, cristae lysis, and disorganization in both C57WT and MNX hearts. Tissue analysis shows that C3HWT hearts have increased autophagy, antioxidant, and glucose fatty acid oxidation-related genes compared with C57WT. Comparative transcriptomic analysis of cardiomyocytes from ACF was dependent upon mtDNA haplotype. C57mtDNA haplotype was associated with increased inflammatory/protein synthesis pathways and downregulation of bioenergetic pathways, whereas C3HmtDNA showed upregulation of autophagy genes. In conclusion, ACF in vivo shows a protective response of C3Hmt haplotype that is in large part driven by mitochondrial nuclear genome interaction.NEW & NOTEWORTHY The results of this study support the effects of mtDNA haplotype on nuclear gene expression in cardiomyocytes. Currently, there is no acceptable therapy for volume overload due to mitral regurgitation. The findings of this study could suggest that mtDNA haplotype activates different pathways after ACF warrants further investigations on human population of heart disease from different ancestry backgrounds.
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Insuficiência Cardíaca , Miócitos Cardíacos , Camundongos , Animais , Humanos , Miócitos Cardíacos/metabolismo , Haplótipos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , DNA Mitocondrial/genéticaRESUMO
PURPOSE: Patients with Moyamoya Angiopathy (MMA) require hemodynamic assessment to evaluate the risk of stroke. Hemodynamic evaluation by use of breath-hold-triggered fMRI (bh-fMRI) was proposed as a readily available alternative to the diagnostic standard [15O]water PET. Recent studies suggest voxel-wise hemodynamic delay correction in hypercapnia-triggered fMRI. The aim of this study was to evaluate the effect of delay correction of bh-fMRI in patients with MMA and to compare the results with [15O]water PET. METHODS: bh-fMRI data sets of 22 patients with MMA were evaluated without and with voxel-wise delay correction within different shift ranges and compared to the corresponding [15O]water PET data sets. The effects were evaluated combined and in subgroups of data sets with most severely impaired CVR (apparent steal phenomenon), data sets with territorial time delay, and data sets with neither steal phenomenon nor delay between vascular territories. RESULTS: The study revealed a high mean cross-correlation (r = 0.79, p < 0.001) between bh-fMRI and [15O]water PET. The correlation was strongly dependent on the choice of the shift range. Overall, no shift range revealed a significantly improved correlation between bh-fMRI and [15O]water PET compared to the correlation without delay correction. Delay correction within shift ranges with positive high high cutoff revealed a lower agreement between bh-fMRI and PET overall and in all subgroups. CONCLUSION: Voxel-wise delay correction, in particular with shift ranges with high cutoff, should be used critically as it can lead to false-negative results in regions with impaired CVR and a lower correlation to the diagnostic standard [15O]water PET.
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Imageamento por Ressonância Magnética , Doença de Moyamoya , Humanos , Imageamento por Ressonância Magnética/métodos , Água , Circulação Cerebrovascular , Hemodinâmica , Encéfalo/irrigação sanguíneaRESUMO
PURPOSE: Cognitive outcomes of pediatric moyamoya disease are variable and difficult to predict on the basis of initial neurological signs and examinations. To determine the best early time point for outcome prediction, we retrospectively analyzed the correlation between cognitive outcomes and the cerebrovascular reserve capacity (CRC) measured before, between, and after staged bilateral anastomoses. METHODS: Twenty-two patients aged 4-15 years were included in this study. CRC was measured before the first hemispheric surgery (preoperative CRC), 1 year after the first surgery (midterm CRC), and 1 year after the surgery on the other side (final CRC). The cognitive outcome was the Pediatric Cerebral Performance Category Scale (PCPCS) grade more than 2 years after the final surgery. RESULTS: The 17 patients with favorable outcomes (PCPCS grades 1 or 2) showed a preoperative CRC of 4.9% ± 11.2%, which was not better than that of the five patients with unfavorable outcomes (grade 3; 0.3% ± 8.5%, p = 0.5). The 17 patients with favorable outcomes showed a midterm CRC of 23.8% ± 15.3%, which was significantly better than that of the five patients with unfavorable outcomes (-2.5% ± 12.1%, p = 0.004). The difference was much more significant for the final CRC, which was 24.8% ± 13.1% in the patients with favorable outcomes and -11.3% ± 6.7% in those with unfavorable outcomes (p = 0.00004). CONCLUSION: Cognitive outcomes were first clearly discriminated by the CRC after the first-side unilateral anastomosis, which is the optimal early timing for the prediction of individual prognosis.
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Revascularização Cerebral , Doença de Moyamoya , Humanos , Criança , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/cirurgia , Doença de Moyamoya/etiologia , Estudos Retrospectivos , Prognóstico , Circulação Cerebrovascular/fisiologia , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
Mitochondrial metabolism must constantly adapt to stress conditions in order to maintain bioenergetic levels related to cellular functions. This absence of proper adaptation can be seen in a wide array of conditions, including cancer. Metabolic adaptation calls on mitochondrial function and draws on the mitochondrial reserve to meet increasing needs. Among mitochondrial respiratory parameters, the spare respiratory capacity (SRC) represents a particularly robust functional parameter to evaluate mitochondrial reserve. We provide an overview of potential SRC mechanisms and regulation with a focus on its particular significance in cancer cells.
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Mitocôndrias/metabolismo , Neoplasias/metabolismo , Animais , Respiração Celular , Humanos , Consumo de OxigênioRESUMO
OBJECTIVES: Aerobic reserve capacity reflects the available energy for performing everyday life tasks, and it has been studied in older adult populations. This preliminary study examined proof of concept and measurement of aerobic reserve capacity in multiple sclerosis (MS). MATERIALS & METHODS: Twenty-one fully ambulatory people with MS performed a maximal, cardiopulmonary exercise test (CPET). We calculated aerobic reserve capacity based on the difference between peak aerobic power (VO2peak ) and first stage oxygen consumption (VO2 ). Participants completed assessments for disability (Expanded Disability Status Scale, EDSS), cognition (Symbol Digit Modalities Test, SDMT), mood (Beck Depression Inventory, BDI), walking endurance (six-minute walk distance, 6MWD), walking speed (Timed Twenty-Foot Walk, T25FW), impact of MS (Multiple Sclerosis Impact Scale, MSIS-29), and anthropometric measurements (height and weight). RESULTS: Aerobic reserve capacity was 9.3 ± 3.7 ml/kg/min. Aerobic reserve capacity was positively associated with VO2peak (ρ = .67, p < .01), time to exhaustion (ρ = .63, p < .01), and SDMT (ρ = .51, p < .05). Aerobic reserve capacity was negatively associated with BMI (ρ = -.62, p < .01) and RHR (ρ = -0.47, p < .05). CONCLUSION: We provide preliminary evidence that aerobic reserve capacity is a feasible outcome derived from maximal CPET (eg, modified Balke protocol) in MS. Aerobic reserve capacity was associated with clinically relevant outcomes and could become an important outcome for rehabilitation in future research.
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Pessoas com Deficiência , Esclerose Múltipla , Idoso , Avaliação da Deficiência , Teste de Esforço , Humanos , Testes Neuropsicológicos , CaminhadaRESUMO
Knockdown of the suppression of tumorigenicity 14-encoding type II transmembrane serine protease matriptase (MTP) in neural stem/progenitor (NS/P) cells impairs cell mobility, response to chemo-attractants, and neurovascular niche interaction. In the present study, we showed by Western blot that a portion of MTP can be detected in the mitochondrial fraction of mouse NS/P cells by immunostaining that it is co-stained with the mitochondrial dye MitoTracker (Thermo Fisher Scientific, Waltham, MA, USA) inside the cells. Co-immunoprecipitation showed that MTP is bound to the ß subunit of mitochondrial F0F1-ATP synthase complex (ATP-ß). Cyto-immunofluorescence staining and an in situ proximity ligation assay further confirmed a physical interaction between MTP and ATP-ß. This interaction relied on the presence of both Cls/Clr urchin embryonic growth factor, bone morphogenic protein 1 and low-density lipoprotein receptor motifs of MTP. We found that NS/P cell mitochondrial membrane potential is impaired by MTP knockdown, and ATP synthesis and oxygen consumption rate are significantly reduced in MTP-knockdown NS/P cells. Among the oxidative phosphorylation functions, the greatest effect of MTP knockdown is the reduction by over 50% in the mitochondrial energy reserve capacity. This made MTP-knockdown NS/P cells unable to overcome hydrogen peroxide stress, which leads to cessation of cell growth. This work identifies 2 previously unknown functions for MTP: first as a binding protein in the mitochondrial F1F0-ATP synthase complex and second as a regulatory mechanism of mitochondrial bioenergetics. Mitochondrial MTP may serve a protective function for NS/P cells in response to stress.-Fang, J.-D., Tung, H.-H., Lee, S.-L. Mitochondrial localization of St14-encoding transmembrane serine protease is involved in neural stem/progenitor cell bioenergetics through binding to F0F1-ATP synthase complex.
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Metabolismo Energético/fisiologia , Proteínas de Membrana/metabolismo , Mitocôndrias/metabolismo , Células-Tronco Neurais/metabolismo , ATPases Translocadoras de Prótons/metabolismo , Serina Endopeptidases/metabolismo , Serina Proteases/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Células Cultivadas , Peróxido de Hidrogênio/metabolismo , Potencial da Membrana Mitocondrial/fisiologia , Camundongos , Fosforilação Oxidativa , Consumo de Oxigênio/fisiologiaRESUMO
Emerging adulthood has been described as a difficult stage in life and may be particularly stressful for Hispanic emerging adults who are disproportionately exposed to adversity and chronic sociocultural stressors. To better prevent and treat depressive disorders among Hispanic emerging adults, more research is needed to identify and understand modifiable determinants that can help this population enhance their capacity to offset and recover from adversity and sociocultural stressors. As such, this study aimed to (1) examine the association between resilience and depressive symptoms among Hispanic emerging adults, and (2) examine the extent to which intrapersonal resources (e.g., mindfulness, distress tolerance, emotion regulation strategies) and interpersonal resources (e.g., family cohesion, social support) moderate the association between resilience and depressive symptoms. To examine these aims, 200 Hispanic emerging adults (ages 18-25) from Arizona (n = 99) and Florida (n = 101) completed a cross-sectional survey, and data were analyzed using hierarchical multiple regression and moderation analyses. Findings from the hierarchical multiple regression indicate that higher resilience was associated with lower depressive symptoms. Findings from the moderation analyses indicate that family cohesion, social support, and emotion regulation strategies (e.g., cognitive reappraisal and expressive suppression) functioned as moderators; however, mindfulness and distress tolerance were not significant moderators. Findings from this study add to the limited literature on resilience among Hispanics that have used validated measures of resilience. Furthermore, we advance our understanding of who may benefit most from higher resilience based on levels of intrapersonal and interpersonal resources.
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Depressão/epidemiologia , Hispânico ou Latino/psicologia , Resiliência Psicológica/ética , Adolescente , Arizona , Estudos Transversais , Regulação Emocional/fisiologia , Emoções/fisiologia , Família/psicologia , Feminino , Florida , Humanos , Masculino , Atenção Plena/tendências , Angústia Psicológica , Apoio Social , Estresse Psicológico/psicologia , Inquéritos e Questionários , Adulto JovemRESUMO
The diagnosis of mitochondrial diseases is a real challenge because of the vast clinical and genetic heterogeneity. Classically, the clinical examination and genetic analysis must be completed by several biochemical assays to confirm the diagnosis of mitochondrial disease. Here, we tested the validity of microscale XF technology in measuring oxygen consumption in human skin fibroblasts isolated from 5 pediatric patients with heterogeneous mitochondrial disorders. We first set up the protocol conditions to allow the determination of respiratory parameters including respiration associated with ATP production, proton leak, maximal respiration, and spare respiratory capacity with reproducibility and repeatability. Maximum respiration and spare capacity were the only parameters decreased in patients irrespective of the type of OXPHOS deficiency. These results were confirmed by high-resolution oxygraphy, the reference method to measure cellular respiration. Given the fact that microscale XF technology allows fast, automated and standardized measurements, we propose to use microscale oxygraphy among the first-line methods to screen OXPHOS deficiencies.
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Fibroblastos/patologia , Mitocôndrias/patologia , Doenças Mitocondriais/diagnóstico , Fosforilação Oxidativa , Oxigênio/análise , Adolescente , Biópsia , Técnicas de Cultura de Células , Linhagem Celular , Estudos de Viabilidade , Feminino , Fibroblastos/citologia , Humanos , Lactente , Recém-Nascido , Masculino , Doenças Mitocondriais/patologia , Oxigênio/metabolismo , Consumo de Oxigênio , Reprodutibilidade dos Testes , Estudos Retrospectivos , Pele/citologia , Pele/patologiaRESUMO
BACKGROUND: Family socioeconomic status (SES) is related to a child's educational success. Intermediate pathways for this relationship, such as through pubertal timing and reserve capacity, occur in adolescence. AIM: To study whether family SES affects a child's adult education through a psychosocial and behavioural pathway (reserve capacity) and/or a biological pathway (pubertal timing) or only through school achievement in adolescence. SUBJECTS AND METHODS: Finnish adolescents sampled in five cross-sectional surveys from 1985 to 1995 (n = 37,876) were followed through the Registry of Completed Education and Degrees until 2009, when they were 29-43 years old. Family SES data also came from this registry. Structural equation modelling adjusted for ages at baseline and follow-up was used. RESULTS: Low family SES increased the probability of low adult education, delayed pubertal timing (in boys), weak reserve capacity and low school achievement. Reserve capacity and school achievement directly affected adult education and mediated the relationship of family SES with the outcome. Delayed pubertal timing predicted low adult education, except when school achievement was added to the model. CONCLUSIONS: The results show that family SES affects the child's adult education level through psychosocial and biobehavioural pathways, but the biological pathway is mediated by school achievement.
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Sucesso Acadêmico , Escolaridade , Maturidade Sexual , Classe Social , Apoio Social , Adolescente , Adulto , Estudos Transversais , Feminino , Finlândia , Humanos , Estudos Longitudinais , Masculino , Adulto JovemRESUMO
Compensatory gomerular filtration rate (GFR) increase after kidney donation results in a GFR above 50% of the predonation value. The renal functional reserve (RFR) assessed by the renal response to dopamine infusion (RFRdopa) is considered to reflect functional reserve capacity and is thought to be a tool for living donor screening. However, it is unknown if the RFRdopa predicts long-term kidney function. Between 1984 and 2017, we prospectively measured GFR (125I-iothalamate) and RFR by dopamine infusion in 937 living kidney donors. We performed linear regression analysis of predonation RFRdopa and postdonation GFR. In donors with 5-yr follow-up after donation we assessed the association with long-term GFR. Mean donor age was 52 yr (SD 11); 52% were female. Mean predonation GFR was 114 ml/min (SD 22), GFRdopa was 124 ml/min (SD 24), resulting in an RFR of 9 ml/min (SD 10). Three months postdonation, GFR was 72 ml/min (SD 15) and GFRdopa was 75 ml/min (SD 15), indicating that donors still had RFRdopa [3 ml/min (SD 6), P < 0.001]. Predonation RFRdopa was not associated with predonation GFR [standardized (st.) ß -0.009, P = 0.77] but was positively associated with GFR 3 mo after donation (st. ß 0.12, P < 0.001). In the subgroup of donors with 5-yr follow-up data ( n = 383), RFRdopa was not associated with GFR at 5 yr postdonation (st. ß 0.05, P = 0.35). In conclusion, RFRdopa is a predictor of short-term GFR after living kidney donation but not of long-term kidney function. Therefore, measurement of the RFRdopa is not a useful tool for donor screening. Studies investigating long-term renal adaptation are warranted to study the effects of living kidney donation and improve donor screening.
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Seleção do Doador/métodos , Taxa de Filtração Glomerular , Transplante de Rim/métodos , Rim/cirurgia , Doadores Vivos , Nefrectomia , Adulto , Dopamina/administração & dosagem , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Infusões Intravenosas , Rim/efeitos dos fármacos , Rim/fisiopatologia , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Nefrectomia/efeitos adversos , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
The aim of structural identification is to provide accurate knowledge of the behaviour of existing structures. In most situations, finite-element models are updated using behaviour measurements and field observations. Error-domain model falsification (EDMF) is a multi-model approach that compares finite-element model predictions with sensor measurements while taking into account epistemic and stochastic uncertainties-including the systematic bias that is inherent in the assumptions behind structural models. Compared with alternative model-updating strategies such as residual minimization and traditional Bayesian methodologies, EDMF is easy-to-use for practising engineers and does not require precise knowledge of values for uncertainty correlations. However, wrong parameter identification and flawed extrapolation may result when undetected outliers occur in the dataset. Moreover, when datasets consist of a limited number of static measurements rather than continuous monitoring data, the existing signal-processing and statistics-based algorithms provide little support for outlier detection. This paper introduces a new model-population methodology for outlier detection that is based on the expected performance of the as-designed sensor network. Thus, suspicious measurements are identified even when few measurements, collected with a range of sensors, are available. The structural identification of a full-scale bridge in Exeter (UK) is used to demonstrate the applicability of the proposed methodology and to compare its performance with existing algorithms. The results show that outliers, capable of compromising EDMF accuracy, are detected. Moreover, a metric that separates the impact of powerful sensors from the effects of measurement outliers have been included in the framework. Finally, the impact of outlier occurrence on parameter identification and model extrapolation (for example, reserve capacity assessment) is evaluated.
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BACKGROUND: Despite robust evidence on the inverse relationship between socioeconomic status (SES) and mortality, deviations from expected results have been observed likely due to school achievement and psychosocial resources, termed as "reserve capacity." Since adolescence is a critical period in developing sound psychological and behavioural patterns and adolescent markers of SES were seldom used, we determine if family SES in adolescence predicts later mortality. We also study how reserve capacity (perceived health, health-promoting behaviour and social support) and school achievement modify this relationship and reduce the negative effects of low SES. METHODS: A longitudinal study was designed by linking baseline data on 12 to 18 year-old Finns in 1985-95 (N = 41,833) from the Adolescent Health and Lifestyle Surveys with register data on mortality and SES from Statistics Finland. Average follow-up time was 18.4 years with a total of 770,161 person-years. Cox regression models, stratified by sex, were fitted to determine the effects of variables measured during adolescence: family SES, reserve capacity and school achievement on mortality risk. RESULTS: All reserve capacity dimensions significantly predicted mortality in boys. Perceived health and social support predicted that in girls. Adolescents with the lowest school achievement were more than twice at risk of dying compared to those with better school performance. Low SES increased the risk of death in boys (Hazard ratios: 1.6, 95% CI 1.1-2.4) but not in girls. Reserve capacity and school achievement weakened the effects of low SES on boys' risk of death. CONCLUSIONS: High reserve capacity and good school achievement in adolescence significantly reduce the risk of mortality. In boys, these also mitigate the negative effect of low SES on mortality. These findings underscore the roles of reserve capacity and school achievement during adolescence as likely causal or modifying factors in SES-health inequalities.
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Sucesso Acadêmico , Autoavaliação Diagnóstica , Comportamentos Relacionados com a Saúde , Mortalidade/tendências , Classe Social , Apoio Social , Adolescente , Adulto , Criança , Feminino , Finlândia/epidemiologia , Inquéritos Epidemiológicos , Humanos , Estudos Longitudinais , MasculinoRESUMO
Patients with symptomatic internal carotid artery (ICA) occlusion with haemodynamic impairment are at higher risk of ischaemic stroke, and they require treatment. There are two main options: the best medical treatment and an extracranial-intracranial bypass. The aims of this study are to analyse the 30-day and 2-year risk of stroke and death in patients with extracranial-intracranial bypass performed by our department and to compare our results with major published studies. This retrospective study enrolled patients who underwent surgery from 1998 to 2012. Inclusion criteria were the following: (1) radiological diagnosis of symptomatic atherosclerotic internal carotid artery occlusion (AICAO), (2) less than 50 % stenosis of a contralateral ICA, (3) transient ischaemic attack (TIA) or ischaemic stroke in the hemispheric territory on an occluded side within 120 days and (4) haemodynamic impairment of at least stage I according to transcranial Doppler sonography (TCDS), perfusion CT and SPECT. Patients were followed up in the outpatient department with TCDS and sonography of the contralateral ICA and the anastomosis after 6 weeks and every 12 months after that. All risks of stroke and death from surgery were recorded throughout the 30 days and the following 2 years post surgery. From September 1998 to November 2012, 93 patients were selected for bypass surgery. There were 72 men and 21 women in an age range of 33 to 79 years (mean 58.9 years) and a follow-up range of 13 to 187 months (mean 108 months). The 30-day risk of stroke and death was 7.5 %. It consists of one death, one major ischaemic stroke, two reversible neurological deficits and three TIAs. The 2-year risk of stroke and death was 9.7 %. Extracranial-intracranial bypass is an effective treatment of haemodynamic impairment in patients with internal carotid occlusion. Maintaining low-level morbidity and mortality is possible with a dedicated neurovascular team. This is the only way in which we can reduce the risk of stroke and death in patients with bypass compared to patients treated medically.
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Artéria Carótida Interna/cirurgia , Arteriosclerose Intracraniana/cirurgia , Ataque Isquêmico Transitório/cirurgia , Acidente Vascular Cerebral/cirurgia , Adulto , Idoso , Doenças das Artérias Carótidas/cirurgia , Estenose das Carótidas/cirurgia , Revascularização Cerebral/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Lack of techniques to assess maximal blood flow capacity thwarts the use of rodent models of arterial insufficiency to evaluate therapies for intermittent claudication. We evaluated femoral vein outflow (VO) in combination with stimulated muscle contraction as a potential method to assess functional hind limb arterial reserve and therapeutic efficacy in a rodent model of subcritical limb ischemia. MATERIALS AND METHODS: VO was measured with perivascular flow probes at rest and during stimulated calf muscle contraction in young, healthy rats (Wistar Kyoto, WKY; lean Zucker rats, LZR) and rats with cardiovascular risk factors (spontaneously hypertensive [SHR]; obese Zucker rats [OZR]) with acute and/or chronic femoral arterial occlusion. Therapeutic efficacy was assessed by administration of Ramipril or Losartan to SHR after femoral artery excision. RESULTS: VO measurement in WKY demonstrated the utility of this method to assess hind limb perfusion at rest and during calf muscle contraction. Although application to diseased models (OZR and SHR) demonstrated normal resting perfusion compared with contralateral limbs, a significant reduction in reserve capacity was uncovered with muscle stimulation. Administration of Ramipril and Losartan demonstrated significant improvement in functional arterial reserve. CONCLUSIONS: The results demonstrate that this novel method to assess distal limb perfusion in small rodents with subcritical limb ischemia is sufficient to unmask perfusion deficits not apparent at rest, detect impaired compensation in diseased animal models with risk factors, and assess therapeutic efficacy. The approach provides a significant advance in methods to investigate potential mechanisms and novel therapies for subcritical limb ischemia in preclinical rodent models.
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Veia Femoral/fisiologia , Membro Posterior/irrigação sanguínea , Doença Arterial Periférica/diagnóstico por imagem , Animais , Estudos de Viabilidade , Artéria Femoral/cirurgia , Veia Femoral/diagnóstico por imagem , Membro Posterior/diagnóstico por imagem , Hiperemia , Ligadura , Losartan , Masculino , Contração Muscular , Ramipril , Ratos Endogâmicos WKY , UltrassonografiaRESUMO
PRIMARY OBJECTIVE: Does younger age at the time of severe traumatic brain injury (STBI) protect from cognitive symptoms? To answer this question, the authors compared the neuropsychological profile of late school-age children/adolescents and young adult patients at mid- and long-term recovery periods (6 and 12 months post-STBI). METHODS AND PROCEDURES: Twenty-eight children/adolescents and 26 clinically matched adults were tested on measures of general intelligence, attention, executive functions, visuoperceptual, visuospatial and visuoconstructive abilities. Coma duration and the post-acute Glasgow Outcome Scale (GOS) score were used as predictor variables in a series of regression analyses. MAIN OUTCOMES AND RESULTS: Children/adolescents and adults similarly improved on most measures, except for visuospatial and visuoconstructive skills, which worsened in time for children/adolescents. Coma duration significantly predicted performance IQ and visuoperceptual scores in children/adolescents. The GOS score significantly predicted performance and verbal IQ, sustained attention, visuoconstructive and long-term memory skills. Coma duration predicted executive function skills in both age groups. CONCLUSIONS: (1) No evidence was found for a neuroprotective effect of younger age at STBI; and (2) Coma duration and GOS score predicted neuropsychological recovery in children/adolescents and adults, respectively. This suggests the existence of underlying age-specific recovery processes after STBI.
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Lesões Encefálicas/fisiopatologia , Função Executiva , Memória de Longo Prazo , Recuperação de Função Fisiológica , Adolescente , Adulto , Fatores Etários , Atenção , Lesões Encefálicas/epidemiologia , Criança , Pré-Escolar , Cognição , Feminino , Seguimentos , Escala de Coma de Glasgow , Escala de Resultado de Glasgow , Humanos , Inteligência , Masculino , Testes Neuropsicológicos , Valor Preditivo dos Testes , Desempenho Psicomotor , Fatores de Tempo , Índices de Gravidade do TraumaRESUMO
Reduced age-specific mortality and increased muscle strength and walking speed of current older adults may have altered the relationships between these factors as more people may be above the reserve capacity threshold. We compared the cross-sectional associations between muscle strength and walking speed, and the associations of muscle strength and walking speed with five-year mortality between two population-based cohorts of 75- and 80-year-old people born 28 years apart. Maximal isometric grip and knee extension strength and walking speed were measured in 2017-2018 (n = 726). Mortality was ascertained from registers. The associations were compared with data of same-aged people studied in 1989-1990 with identical protocols (n = 500). The knee extension strength-walking speed relationship showed plateauing at higher strength levels among the later-born men, whereas the earlier-born men and women of both cohorts with lower strength levels were on the linear part of the curve. In the later-born women with lower five-year mortality rate (1.16 vs. 5.88 per 100 person-years), the association between grip strength and mortality was markedly different from the earlier cohort (HR 1.13 [95% CI 0.47-2.70] vs. 0.57 [0.37-0.86]). For knee extension strength and walking speed, the mortality hazards were similar between the cohorts, although statistically non-significant in the later-born women. In men, the later-born cohort showed similar associations as observed in the earlier-born cohort despite having lower mortality rate (2.93 vs. 6.44). Current older adults have more functional reserve that will likely help them to maintain walking ability for longer while also contributing to better survival.
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Vida Independente , Velocidade de Caminhada , Masculino , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Velocidade de Caminhada/fisiologia , Coorte de Nascimento , Estudos Transversais , Força Muscular/fisiologiaRESUMO
This review aims to explore advancements in perioperative ischemic stroke risk estimation for asymptomatic patients with significant carotid artery stenosis, focusing on Circle of Willis (CoW) morphology based on the CTA or MR diagnostic imaging in the current preoperative diagnostic algorithm. Functional transcranial Doppler (fTCD), near-infrared spectroscopy (NIRS), and optical coherence tomography angiography (OCTA) are discussed in the context of evaluating cerebrovascular reserve capacity and collateral vascular systems, particularly the CoW. These non-invasive diagnostic tools provide additional valuable insights into the cerebral perfusion status. They support biomedical modeling as the gold standard for the prediction of the potential impact of carotid artery stenosis on the hemodynamic changes of cerebral perfusion. Intraoperative risk assessment strategies, including selective shunting, are explored with a focus on CoW variations and their implications for perioperative ischemic stroke and cognitive function decline. By synthesizing these insights, this review underscores the potential of non-invasive diagnostic methods to support clinical decision making and improve asymptomatic patient outcomes by reducing the risk of perioperative ischemic neurological events and preventing further cognitive decline.
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Before revascularization, moyamoya patients require hemodynamic evaluation. In this study, we evaluated the scoring system Prior Infarcts, Reactivity and Angiography in Moyamoya Disease (PIRAMID). We also devised a new scoring system, MRI-Based Assessment of Risk for Stroke in Moyamoya Angiopathy (MARS-MMA), and compared the scoring systems with respect to the capability to predict impaired [15O]water PET cerebral perfusion reserve capacity (CPR). We evaluated 69 MRI, 69 DSA and 38 [15O]water PET data sets. The PIRAMID system was validated by ROC curve analysis with neurological symptomatology as a dependent variable. The components of the MARS-MMA system and their weightings were determined by binary logistic regression analysis. The comparison of PIRAMID and MARS-MMA was performed by ROC curve analysis. The PIRAMID score correlated well with the symptomatology (AUC = 0.784). The MARS-MMA system, including impaired breath-hold-fMRI, the presence of the Ivy sign and arterial wall contrast enhancement, correlated slightly better with CPR impairment than the PIRAMID system (AUC = 0.859 vs. 0.827, Akaike information criterion 140 vs. 146). For simplified clinical use, we determined three MARS-MMA grades without loss of diagnostic performance (AUC = 0.855). The entirely MRI-based MARS-MMA scoring system might be a promising tool to predict the risk of stroke.
RESUMO
BACKGROUND: Multiples of resting metabolic rate (RMR) are often used to classify physical activity intensity, a concept known as the metabolic equivalent of task (MET). However, the METs metrics may misclassify physical activity intensity in older adults because of age-related changes in RMR and maximal aerobic capacity (VËO2max). This study aimed to (i) compare classifications of activity intensity by estimated (METsestimated) and measured (METsmeasured) METs and (ii) compare physical activity classified by absolute (METsmeasured) versus relative intensity (%VËO2Reserve) in older adults. METHODS: Ninety-eight adults aged 75-90 years participated in the study. RMR and VËO2 during sitting, standing, daily activities, and 6-minute walking test were measured. VËO2Reserve was defined as the difference between VËO2max and RMR. Moderate and vigorous intensity was classified as 3 and 6 METs and 40% and 60% of VËO2Reserve, respectively. Paired t tests and a confusion matrix were used to investigate aims 1 and 2, respectively. RESULTS: METsmeasured was 24% lower than the standard 1 MET of 3.5 mL O2·min-1·kg-1. METsestimated underestimated the intensity during daily and walking activities when compared to METsmeasured. Nevertheless, when comparing METsmeasured to percentages of VËO2Reserve, a mismatch was shown for moderate intensity in 47%-67% of the participants during daily activities and 21% of the participants during self-selected gait speed. CONCLUSIONS: Applying METsestimated for older adults leads to potential underestimation of physical activity intensity, suggesting that current classification metrics should be revised for older adults. VËO2Reserve is a candidate metric for establishing precise physical activity intensity cut points for older adults. Clinical Trials Registration Number: NCT04821713.