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1.
J Nutr Health Aging ; 27(10): 885-893, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37960912

RESUMO

OBJECTIVES: To provide a comprehensive CERT (Consensus on Exercise Reporting Template)-based description of the resistance exercise program implemented in the AGUEDA (Active Gains in brain Using Exercise During Aging) study, a randomized controlled trial investigating the effects of a 24-week supervised resistance exercise program on executive function and related brain structure and function in cognitively normal older adults. DESIGN AND PARTICIPANTS: 90 cognitively normal older adults aged 65 to 80 were randomized (1:1) to a: 1) resistance exercise group; or a 2) wait-list control group. Participants in the exercise group (n = 46) performed 180 min/week of resistance exercise (3 supervised sessions per week, 60 min/session) for 24 weeks. INTERVENTION: The exercise program consisted of a combination of upper and lower limb exercises using elastic bands and the participant's own body weight as the main resistance. The load and intensity were based on the resistance of the elastic bands (7 resistances), number of repetitions (individualized), motor complexity of exercises (3 levels), sets and rest (3 sets/60 sec rest), execution time (40-60 sec) and velocity (as fast as possible). SETTINGS: The maximum prescribed-target intensity was 70-80% of the participants' maximum rate of perceived exertion (7-8 RPE). Heart rate, sleep quality and feeling scale were recorded during all exercise sessions. Those in the wait-list control group (n = 44) were asked to maintain their usual lifestyle. The feasibility of AGUEDA project was evaluated by retention, adherence, adverse events and cost estimation on the exercise program. RESULTS AND CONCLUSIONS: This study details the exercise program of the AGUEDA trial, including well-described multi-language manuals and videos, which can be used by public health professionals, or general public who wish to implement a feasible and low-cost resistance exercise program. The AGUEDA exercise program seems to be feasible by the high retention (95.6%) and attendance rate (85.7%), very low serious adverse event (1%) and low economic cost (144.23 € /participant/24 weeks). We predict that a 24-week resistance exercise program will have positive effects on brain health in cognitively normal older adults.


Assuntos
Treinamento Resistido , Humanos , Idoso , Treinamento Resistido/métodos , Exercício Físico/fisiologia , Terapia por Exercício/métodos , Envelhecimento , Peso Corporal , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
Mult Scler ; 29(13): 1569-1577, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37880953

RESUMO

BACKGROUND: As exercise exerts neurobiological and immunomodulatory effects, it might also act as a disease-modifying intervention in MS. However, a clear mechanistic link between exercise and disease-modifying effects in MS has yet to be established. OBJECTIVE: Establish recommendations for future mechanistic exercise studies in MS. METHODS: In regular meetings, members of the mechanisms of action group within the MoXFo (Moving eXercise research Forward in MS) initiative evaluated gaps of knowledge and discussed unmet needs in mechanistic MS research. RESULTS: We concluded that biomarkers assessed in translational studies in humans and animals are essential to decipher the underlying mechanisms of exercise in MS. Consequently, we defined clear definitions of different types of biomarkers examined in MS exercise studies and operationalized their use to align with the research question and optimal testing time points. Furthermore, we provide key considerations to improve the rigor of translational studies and defined minimal reporting criteria for animal studies. CONCLUSION: The resulting recommendations are intended to improve the quality of future mechanistic exercise studies in MS and consequently lead to a better understanding of therapeutic approaches.


Assuntos
Esclerose Múltipla , Humanos , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/terapia , Terapia por Exercício/métodos , Exercício Físico , Biomarcadores
3.
Environ Pollut ; 324: 121419, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-36906055

RESUMO

Anthropogenic environmental stressors have significantly reduced biodiversity and the capacity of remnant natural habitats to deliver ecosystem functions and services in urban areas. To mitigate these impacts and recover biodiversity and function, ecological restoration strategies are needed. While habitat restoration is proliferating in rural and peri-urban areas, strategies purposely designed to succeed under the environmental, social and political pressures of urban areas are lacking. Here, we propose that ecosystem health in marine urban areas can be improved by restoring biodiversity to the most dominant habitat, unvegetated sediments. We reintroduced a native ecosystem engineer, the sediment bioturbating worm Diopatra aciculata, and assessed their effects on microbial biodiversity and function. Results showed that worms can affect the diversity of microbes, but effects varied between locations. Worms caused shifts in microbial community composition and function at all locations. Specifically, the abundance of microbes capable of chlorophyll production (i.e. benthic microalgae) increased and the abundance of microbes capable of methane production decreased. Moreover, worms increased the abundances of microbes capable of denitrification in the site with lowest sediment oxygenation. Worms also affected microbes capable of degrading the polycyclic aromatic hydrocarbon toluene, although the direction of that effect was site-specific. This study provides evidence that a simple intervention such as the reintroduction of a single species can enhance sediment functions important for the amelioration of contamination and eutrophication, although further studies are needed to understand the variation in outcomes between sites. Nevertheless, restoration strategies targeting unvegetated sediments provide an opportunity to combat anthropogenic stressors in urban ecosystems and may be used for precondition before more traditional forms of habitat restoration such as seagrass, mangrove and shellfish restoration.


Assuntos
Ecossistema , Sedimentos Geológicos , Biodegradação Ambiental , Biodiversidade , Eutrofização
4.
Urology ; 160: 161-167, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34896123

RESUMO

OBJECTIVE: To evaluate patients' and partners' satisfaction with a prostate cancer survivorship program embedded in urologic-oncologic care. As a part of quality improvement activity, we developed a patient and partner-centered, biopsychosocial support program for men and partners coping with the urinary and sexual side-effects of surgical treatment for prostate cancer. The program became a part of usual care for all prostate cancer patients. METHODS: Patients who saw both an advanced practice provider and a sex therapist between August 1, 2018 and July 31, 2019 were eligible. Surveys packets were sent to 146 patients with surveys included for partners (N = 292). We used descriptive statistics to characterize participant responses. RESULTS: Responses were received from 88 patients and 70 partners (56% response rate for the group). Patients and partners reported very high or fairly high satisfaction with the rehabilitation activities of the program (86-97% and 90%-100%, respectively); 91% of patients and 84% of partners thought having pre-operative education and post-operative rehabilitation was a good or fairly good idea; 83% of patients and 79% of partners would very much or somewhat recommend the program to a friend who was considering surgical treatment for prostate cancer. CONCLUSION: Embedding a patient and partner-centered prostate cancer survivorship support program in oncologic care can positively impact patients' and partners' engagement in and satisfaction with post-operative rehabilitation.


Assuntos
Próstata , Neoplasias da Próstata , Humanos , Masculino , Satisfação do Paciente , Assistência Centrada no Paciente , Satisfação Pessoal , Neoplasias da Próstata/psicologia , Neoplasias da Próstata/cirurgia , Parceiros Sexuais/psicologia , Sobrevivência
6.
J Viral Hepat ; 25(11): 1270-1279, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29851265

RESUMO

Elbasvir/grazoprevir (EBR/GZR) is an all-oral direct-acting antiviral agent (DAA) with high sustained virologic response (SVR) in clinical trials. This study's primary objective was to evaluate effectiveness of EBR/GZR among HCV-infected patients in a real-world clinical setting. We conducted a nationwide retrospective observational cohort study of HCV-infected patients in the US Department of Veterans Affairs (VA) using the VA Corporate Data Warehouse. The study population included patients with positive HCV RNA who initiated EBR/GZR from February 1 to August 1, 2016. We calculated the 95% confidence interval for binomial proportions for SVR overall and by demographic subgroups. Clinical and demographic characteristics were also evaluated. We included 2436 patients in the study cohort. Most were male (96.5%), African American (57.5%), with mean age of 63.5 (SD = 5.9) and 95.4% infected with genotype (GT) 1 [GT1a (34.7%), GT1b (58.6%)]. Other comorbidities included diabetes (53.2%), depression (57.2%) and HIV (3.0%). More than 50% had history of drug or alcohol abuse (53.9% and 60.5%, respectively). 33.2% of the cohort had cirrhosis. A total of 95.6% (2,328/2,436; 95% CI: 94.7%-96.4%) achieved SVR. The SVR rates by subgroups were: male, 95.5% (2245/2350); female, 96.5% (83/86); GT1a, 93.4%, GT1b, 96.6%, GT4, 96.9%, African American, 95.9% (1,342/1,400); treatment-experienced, 96.3% (310/322); cirrhosis, 95.6% (732/766); stage 4-5 CKD, 96.3% (392/407); and HIV, 98.6% (73/74). SVR rates were high overall and across patient subgroups regardless of gender, race/ethnicity, cirrhosis, renal impairment or HIV. This study provided important data regarding the effectiveness of EBR/GZR in a large clinical setting.


Assuntos
Antivirais/uso terapêutico , Benzofuranos/uso terapêutico , Hepatite C/tratamento farmacológico , Imidazóis/uso terapêutico , Quinoxalinas/uso terapêutico , Veteranos/estatística & dados numéricos , Idoso , Amidas , Antivirais/farmacologia , Benzofuranos/farmacologia , Carbamatos , Ciclopropanos , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C/epidemiologia , Hepatite C/virologia , Humanos , Imidazóis/farmacologia , Masculino , Pessoa de Meia-Idade , Quinoxalinas/farmacologia , Estudos Retrospectivos , Sulfonamidas , Resposta Viral Sustentada , Estados Unidos/epidemiologia
7.
AJNR Am J Neuroradiol ; 38(10): 1923-1928, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28775055

RESUMO

BACKGROUND AND PURPOSE: Traditional neuroimaging markers of small-vessel disease focus on late-stage changes. We aimed to adapt a method of venular assessment at 7T for use in older adults. We hypothesized that poorer venular morphologic characteristics would be related to other small-vessel disease neuroimaging markers and a higher prevalence of small-vessel disease-Alzheimer disease risk factors. MATERIALS AND METHODS: Venules were identified in periventricular ROIs on SWI and defined as tortuous or straight. The tortuosity ratio was defined as total tortuous venular length divided by total straight venular length. White matter hyperintensity burden (visually rated from 0 to 3) and the number of microbleeds (0, 1, >1) were determined. Differences in tortuous and straight venular lengths were evaluated. Relationships with demographic variables, allele producing the e4 type of apolipoprotein E (APOE4), growth factors, pulse pressure, physical activity, and Modified Mini-Mental State Examination were assessed via Spearman correlations. RESULTS: Participants had 42% more tortuous venular tissue than straight (median, 1.42; 95% CI, 1.13-1.62). APOE4 presence was associated with a greater tortuosity ratio (ρ = 0.454, P = .001), and these results were robust to adjustment for confounders and multiple comparisons. Associations of the tortuosity ratio with sex and vascular endothelial growth factor did not survive adjustment. Associations of the tortuosity ratio with other variables of interest were not significant. CONCLUSIONS: Morphologic measures of venules at 7T could be useful biomarkers of the early stages of small-vessel disease and Alzheimer disease. Longitudinal studies should examine the impact of apolipoprotein E and vascular endothelial growth factor on the risk of venular damage.


Assuntos
Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Feminino , Humanos , Masculino , Fatores de Risco
8.
Dalton Trans ; 46(34): 11208-11213, 2017 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-28795722

RESUMO

The reaction of (C5Me5)2AnCl2 (An = Th, U) with 2.8 or 4 equivalents of LiNMe2, respectively, affords (C5Me5)2An(NMe2)2 in high yields. In addition to improved syntheses, the solid-state structures, voltammetric data, and UV-visible-NIR spectra for these classic actinide bis(dimethylamido) complexes are presented for the first time.

10.
Clin Exp Allergy ; 45(11): 1663-72, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25989379

RESUMO

BACKGROUND: Food allergy affects approximately 6-8% of children, and increasing in prevalence. Some children naturally outgrow their food allergy without intervention, but the mechanisms by which this occurs remain poorly understood. We sought to investigate the role of regulatory T cells in the development of naturally acquired tolerance. METHODS: Fifty-eight children (1-18 years) with either egg or peanut allergy, recent acquisition of natural tolerance to egg or peanut, or no food allergy were studied. Peripheral blood mononuclear cells (PBMC) from these groups were stimulated with relevant antigen for 48 h and flow cytometry performed to characterize both surface (CD3, CD4, CD25, CD14, CD19, and CD127) and intracellular markers (IL-10, Foxp3, and IL-5). RESULTS: Resting PBMC from naturally tolerant patients had significantly increased CD3+CD4+CD25+CD127loFoxp3+ cells, when compared to allergic or control patients (mean 6.36 vs. 2.37 vs. 2.62%, respectively, P < 0.05). Upon stimulation with relevant antigen, naturally tolerant patients also had increased IL-10-expressing CD25+CD127lo cells (6.33 vs. 1.65 vs. 0.7, P < 0.01), Foxp3+ cells (mean 12.6 vs. 5.42 vs. 3%, P < 0.01), and CD4+ cells (mean 4.48 vs. 1.59 vs. 0.87%, P < 0.01); the increase was not observed in PBMCs from allergic or control patients. Additionally, this upregulation was only seen with relevant antigen stimulation and not upon stimulation with unrelated antigen. CONCLUSION: The increased CD3+CD4+CD25+CD127lo cells at baseline and upon stimulation and increased induction of IL-10-producing cells of several types, including Tr1 cells, from naturally tolerant patients suggests an important role for regulatory T cell subsets in the acquisition of natural tolerance.


Assuntos
Alérgenos/imunologia , Contagem de Linfócito CD4 , Hipersensibilidade Alimentar/imunologia , Alimentos/efeitos adversos , Tolerância Imunológica , Linfócitos T Reguladores/imunologia , Adolescente , Antígenos de Superfície/metabolismo , Arachis/imunologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Imunoglobulina E/imunologia , Imunofenotipagem , Lactente , Interleucina-10/biossíntese , Masculino , Fenótipo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Reguladores/metabolismo
11.
Cell Death Dis ; 6: e1666, 2015 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-25719250

RESUMO

Withanolide E, a steroidal lactone from Physalis peruviana, was found to be highly active for sensitizing renal carcinoma cells and a number of other human cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. Withanolide E, the most potent and least toxic of five TRAIL-sensitizing withanolides identified, enhanced death receptor-mediated apoptotic signaling by a rapid decline in the levels of cFLIP proteins. Other mechanisms by which TRAIL sensitizers have been reported to work: generation of reactive oxygen species (ROS), changes in pro-and antiapoptotic protein expression, death receptor upregulation, activation of intrinsic (mitochondrial) apoptotic pathways, ER stress, and proteasomal inhibition proved to be irrelevant to withanolide E activity. Loss of cFLIP proteins was not due to changes in expression, but rather destabilization and/or aggregation, suggesting impairment of chaperone proteins leading to degradation. Indeed, withanolide E treatment altered the stability of a number of HSP90 client proteins, but with greater apparent specificity than the well-known HSP90 inhibitor geldanamycin. As cFLIP has been reported to be an HSP90 client, this provides a potentially novel mechanism for sensitizing cells to TRAIL. Sensitization of human renal carcinoma cells to TRAIL-induced apoptosis by withanolide E and its lack of toxicity were confirmed in animal studies. Owing to its novel activity, withanolide E is a promising reagent for the analysis of mechanisms of TRAIL resistance, for understanding HSP90 function, and for further therapeutic development. In marked contrast to bortezomib, among the best currently available TRAIL sensitizers, withanolide E's more specific mechanism of action suggests minimal toxic side effects.


Assuntos
Apoptose/efeitos dos fármacos , Carcinoma de Células Renais/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Vitanolídeos/farmacologia , Animais , Western Blotting , Linhagem Celular Tumoral , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Imunoprecipitação , Camundongos Endogâmicos BALB C , Espécies Reativas de Oxigênio/farmacologia
12.
Rev Sci Instrum ; 85(11): 11E807, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25430372

RESUMO

This paper describes aspects of magnetic diagnostics for realtime control in National Spherical Torus Experiment-Upgrade (NSTX-U). The sensor arrangement on the upgraded center column is described. New analog and digital circuitry for processing the plasma current Rogowski data are presented. An improved algorithm for estimating the plasma vertical velocity for feedback control is presented.

13.
Psychol Med ; 42(2): 345-57, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21798113

RESUMO

BACKGROUND: Major depressive disorder (MDD) is associated with deficits in recalling specific autobiographical memories (AMs). Extensive research has examined the functional anatomical correlates of AM in healthy humans, but no studies have examined the neurophysiological underpinnings of AM deficits in MDD. The goal of the present study was to examine the differences in the hemodynamic response between patients with MDD and controls while they engage in AM recall. METHOD: Participants (12 unmedicated MDD patients; 14 controls) underwent functional magnetic resonance imaging (fMRI) scanning while recalling AMs in response to positive, negative and neutral cue words. The hemodynamic response during memory recall versus performing subtraction problems was compared between MDD patients and controls. Additionally, a parametric linear analysis examined which regions correlated with increasing arousal ratings. RESULTS: Behavioral results showed that relative to controls, the patients with MDD had fewer specific (p=0.013), positive (p=0.030), highly arousing (p=0.036) and recent (p=0.020) AMs, and more categorical (p<0.001) AMs. The blood oxygen level-dependent (BOLD) response in the parahippocampus and hippocampus was higher for memory recall versus subtraction in controls and lower in those with MDD. Activity in the anterior insula was lower for specific AM recall versus subtraction, with the magnitude of the decrement greater in MDD patients. Activity in the anterior cingulate cortex was positively correlated with arousal ratings in controls but not in patients with MDD. CONCLUSIONS: We replicated previous findings of fewer specific and more categorical AMs in patients with MDD versus controls. We found differential activity in medial temporal and prefrontal lobe structures involved in AM retrieval between MDD patients and controls as they engaged in AM recall. These neurophysiological deficits may underlie AM recall impairments seen in MDD.


Assuntos
Córtex Cerebral/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Neuroimagem Funcional/métodos , Memória Episódica , Rememoração Mental/fisiologia , Adulto , Feminino , Neuroimagem Funcional/instrumentação , Hipocampo/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Giro Para-Hipocampal/fisiopatologia
14.
J Perinatol ; 32(2): 139-46, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21546939

RESUMO

OBJECTIVE: To study postnatal dexamethasone treatment effects on cognitive, neuropsychological and behavioral functioning at early school age in preterm children. STUDY DESIGN: We recruited 222 children born between 1998 and 2003: 114 extremely low birth weight (<1000 g; 60 dexamethasone-treated; 54 untreated) and 108 term-born. Data were analyzed using multivariate methods. RESULT: Preterm performed below term-born on all measures. Dexamethasone-treated performed below dexamethasone-untreated in immediate visual memory, visual-motor integration, mathematical skill and motor dexterity. However, stepwise regression indicated that medical and sociodemographic factors other than dexamethasone contributed to preterm group differences. CONCLUSION: Dexamethasone alone does not explain neurocognitive impairment in preterm children. Medical and sociodemographic factors (illness severity, male gender and parental education) are influential. Prospective longitudinal neuropsychological and behavioral study from preschool to school age that considers medical and sociodemographic variables will best address effects of dexamethasone exposure.


Assuntos
Displasia Broncopulmonar/tratamento farmacológico , Transtornos do Comportamento Infantil/etiologia , Deficiências do Desenvolvimento/etiologia , Dexametasona/efeitos adversos , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Peso ao Nascer , Displasia Broncopulmonar/diagnóstico , Criança , Transtornos do Comportamento Infantil/epidemiologia , Transtornos do Comportamento Infantil/fisiopatologia , Estudos de Coortes , Deficiências do Desenvolvimento/epidemiologia , Deficiências do Desenvolvimento/fisiopatologia , Dexametasona/uso terapêutico , Função Executiva , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Análise Multivariada , Testes Neuropsicológicos , Cuidado Pós-Natal/métodos , Gravidez , Nascimento Prematuro , Valores de Referência , Análise de Regressão , Estudos Retrospectivos , Medição de Risco , Fatores Socioeconômicos , Nascimento a Termo
15.
J Phys Chem B ; 115(12): 3038-51, 2011 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-21370845

RESUMO

Values of the ionization constant of acetic acid in H(2)O and D(2)O (K(HAc) and K(DAc)) and the deuterium isotope effect, ΔpK = pK(DAc) - pK(HAc), have been determined from T = 368 K to T = 548 K at p = 20 MPa, using a flow-through ac conductance cell built at the University of Delaware. Measurements were made on dilute (ionic strength ∼ 10(-4) mol·kg(-1)) solutions of acetic acid, sodium acetate, hydrochloric acid, and sodium chloride in H(2)O and D(2)O, injected in sequence at each temperature and pressure, so that systematic errors in the measured conductance of each solution would cancel. Experimental values for the molar conductivity, Λ, of the strong electrolytes were used to calculate the molar conductivity at infinite dilution, Λ°, using the Fuoss-Hsia-Fernández-Prini (FHFP) equation. These were used to calculate the molar conductivity at infinite dilution for acetic acid which was in turn used to calculate the degree of dissociation and finally the ionization constants of acetic acid. This same procedure was done for the pertinent deuterated solutes in D(2)O. Measured values of log K(HAc), log K(DAc), and ΔpK were obtained to a precision of ±0.008. The present results are in agreement with the only other accurate study at high temperatures and pressures (Mesmer, R. E.; Herting, D. L. J. Solution Chem.1978, 7, 901-913). The deuterium isotope effects, ΔpK, become independent of temperature above ∼420 K, at a value approximately 0.1 unit lower than that at 298 K. These values are ΔpK = 0.43 ± 0.01 and ΔpK = 0.51 ± 0.01, respectively. The temperature dependence of the Walden product ratio, (λ°Î·)(D(2)O)/(λ°Î·)(H(2)O), indicates a change in the relative hydration behavior of ions, whereby the effective Stokes radii of the sodium, chloride, and acetate ions in D(2)O relative to H(2)O reverse above ∼423 K. The results also suggest that the greater efficiency of the well-established proton-hopping transport mechanisms for OH(-) and H(3)O(+) at 298 K, relative to OD(-) and D(3)O(+), is significantly reduced as the temperature increases toward 548 K.

16.
Mol Psychiatry ; 16(4): 407-18, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20351719

RESUMO

Genetic variation in the cholinergic muscarinic-2 (M(2)) receptor gene (CHRM2) has been associated with the risk for developing depression. We previously reported that M(2)-receptor distribution volume (V(T)) was reduced in depressed subjects with bipolar disorder (BD) relative to depressed subjects with major depressive disorder (MDD) and healthy controls (HCs). In this study, we investigated the effects of six single-nucleotide polymorphisms (SNPs) for CHRM2 on M(2)-receptor binding to test the hypotheses that genetic variation in CHRM2 influences M(2)-receptor binding and that a CHRM2 polymorphism underlies the deficits in M(2)-receptor V(T) observed in BD. The M(2)-receptor V(T) was measured using positron emission tomography and [(18)F]FP-TZTP in unmedicated, depressed subjects with BD (n=16) or MDD (n=24) and HCs (n=25), and the effect of genotype on V(T) was assessed. In the controls, one SNP (with identifier rs324650, in which the ancestral allele adenine (A) is replaced with one or two copies of thymine (T), showed a significant allelic effect on V(T) in the pregenual and subgenual anterior cingulate cortices in the direction AA

Assuntos
Transtorno Bipolar/genética , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Receptor Muscarínico M2/genética , Receptor Muscarínico M2/metabolismo , Adolescente , Adulto , Transtorno Bipolar/complicações , Transtorno Bipolar/diagnóstico por imagem , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Feminino , Radioisótopos de Flúor , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons/métodos , Ligação Proteica/efeitos dos fármacos , Ligação Proteica/genética , Escalas de Graduação Psiquiátrica , Estatísticas não Paramétricas , Adulto Jovem
17.
Br J Anaesth ; 105 Suppl 1: i34-49, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21148654

RESUMO

Several multicentre, randomized trials have validated the efficacy of carotid endarterectomy (CEA). Comparative randomized trials are also currently developing insight into the role of carotid angioplasty and stenting (CAS), and identifying factors for optimal patient selection. Although these interventions are aimed at embolic stroke prevention, anaesthetic management might prevent the subset of strokes that are haemodynamic in nature by maintaining tight physiological control. The perioperative risk of myocardial events is increased in this population. Hence, preoperative attention to cardiovascular disease, hypertension, renal insufficiency, and diabetes mellitus might reduce neurological and cardiovascular complications. During carotid artery cross-clamping, the risk of cerebral ischaemia can be decreased by maintaining normal to high perfusion pressure. Although there is no demonstrable advantage of a specific anaesthetic technique for patients undergoing CEA, it is imperative that cerebral blood flow is optimized, that there is minimal cardiac stress, and that anaesthetic recovery is rapid. Carotid angioplasty and stenting is performed under light sedation with antithrombotic therapy and vigilance for bradycardia and hypotension. Tight haemodynamic control remains a priority in the immediate postoperative period for both interventions.


Assuntos
Angioplastia/métodos , Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas/métodos , Stents , Anestesia/métodos , Isquemia Encefálica/prevenção & controle , Estenose das Carótidas/diagnóstico , Endarterectomia das Carótidas/efeitos adversos , Humanos , Monitorização Intraoperatória/métodos , Cuidados Pré-Operatórios/métodos
18.
Neurology ; 75(16): 1415-22, 2010 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-20944075

RESUMO

OBJECTIVES: Physical activity (PA) has been hypothesized to spare gray matter volume in late adulthood, but longitudinal data testing an association has been lacking. Here we tested whether PA would be associated with greater gray matter volume after a 9-year follow-up, a threshold could be identified for the amount of walking necessary to spare gray matter volume, and greater gray matter volume associated with PA would be associated with a reduced risk for cognitive impairment 13 years after the PA evaluation. METHODS: In 299 adults (mean age 78 years) from the Cardiovascular Health Cognition Study, we examined the association between gray matter volume, PA, and cognitive impairment. Physical activity was quantified as the number of blocks walked over 1 week. High-resolution brain scans were acquired 9 years after the PA assessment on cognitively normal adults. White matter hyperintensities, ventricular grade, and other health variables at baseline were used as covariates. Clinical adjudication for cognitive impairment occurred 13 years after baseline. RESULTS: Walking amounts ranged from 0 to 300 blocks (mean 56.3; SD 69.7). Greater PA predicted greater volumes of frontal, occipital, entorhinal, and hippocampal regions 9 years later. Walking 72 blocks was necessary to detect increased gray matter volume but walking more than 72 blocks did not spare additional volume. Greater gray matter volume with PA reduced the risk for cognitive impairment 2-fold. CONCLUSION: Greater amounts of walking are associated with greater gray matter volume, which is in turn associated with a reduced risk of cognitive impairment.


Assuntos
Encéfalo/patologia , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/fisiopatologia , Atividade Motora/fisiologia , Idoso , Idoso de 80 Anos ou mais , Mapeamento Encefálico , Transtornos Cognitivos/etiologia , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética/métodos , Masculino , Entrevista Psiquiátrica Padronizada , Testes Neuropsicológicos , Razão de Chances , Valor Preditivo dos Testes , Inquéritos e Questionários
20.
Int J Obes (Lond) ; 30(9): 1347-55, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16534530

RESUMO

BACKGROUND: Chemotactic cytokines, referred to as chemokines, play an important role in leukocyte trafficking. The circulating levels of chemokines have been shown to increase in inflammatory processes including obesity-related pathologies (e.g. atherosclerosis and diabetes). However, little is currently known about the relationship between chemokines and human obesity. In the present study, we investigated the circulating levels of selected chemokines (monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha), leukotactin-1, interleukin-8 (IL-8)) and the association between the chemokine levels and obesity-related parameters: body mass index (BMI), waist circumference, fasting glucose and insulin levels, lipids profile, and the level of C-reactive protein (CRP). METHODS: A total of 100 subjects, 50 obese (BMI>or=25 kg/m2) and 50 who were not obese (BMI<25 kg/m2) participated in the present study. The levels of chemokines and CRP were measured in a fasting state serum by sandwich enzyme-linked immunosorbent assay. Total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglyceride, glucose, and insulin levels were measured by enzymatic analysis and immunoassay. RESULTS: The circulating levels of MCP-1 and IL-8 in the serum were significantly (P<0.05) higher in obese subjects (BMI>30 kg/m2) compared with those of nonobese controls (BMI<25 kg/m2). The levels of CRP were positively correlated with BMI (P<0.001) or waist circumference (P<0.0001). The levels of MCP-1 and IL-8 were positively related to BMI (MCP-1, P<0.02; IL-8, P<0.01) and/or waist circumference (MCP-1, P<0.009; IL-8, P<0.03). The levels of MCP-1 were positively related to the levels of CRP (P<0.007) or interleukin-6 (IL-6) (P<0.0001), and negatively related to the levels of HDL-cholesterol (P<0.01). Homeostasis model assessment (HOMA) score was positively related to the levels of MCP-1 (P<0.02) or IL-8 (P<0.03) in obese subject. DISCUSSION: Our data demonstrated that the circulating levels of MCP-1 and IL-8 are related to obesity-related parameters such as BMI, waist circumference, CRP, IL-6, HOMA and HDL-cholesterol. These findings suggest that the circulating MCP-1 and/or IL-8 may be a potential candidate linking obesity with obesity-related metabolic complications such as atherosclerosis and diabetes.


Assuntos
Quimiocina CCL2/sangue , Interleucina-8/sangue , Obesidade/sangue , Adulto , Biomarcadores/sangue , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , HDL-Colesterol/sangue , Feminino , Humanos , Masculino , Relação Cintura-Quadril
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