RESUMO
BACKGROUND: Few studies have examined the relationship between motor skill competence and device-measured physical activity in large samples and none have used non-linear modelling. This study assessed the linear and non-linear associations between motor skill competence and physical activity in children using pooled data from eight studies. METHODS: Cross-sectional ActiGraph accelerometer and motor skills competence data from 988 children (50.8% boys) aged 3-11 years were included. Total, object control and locomotor skill competence were assessed using the Test of Gross Motor Skill Development. Linear mixed models were fitted to examine linear associations between motor skill competence and physical activity. Then, restricted cubic splines models were used to assess potential non-linear relationships. Interactions by sex and age were assessed. RESULTS: There was evidence of positive linear associations between total skill, and object control and locomotor skills, with moderate- and vigorous-intensity physical activity; however, the associations with total skill competence and object control better fitted a non-linear model. Non-linear models indicated associations were positive but relatively weak in the low to mid ranges of TGMD/object control scores but at high ranges (~ > 70 out of 100/ and ~ 35 out of 50) the association strength increased for both moderate- and vigorous-intensity physical activity. There were sex interactions for locomotor skills only, specifically for vigorous activity with boys having a stronger positive association than girls. CONCLUSIONS: There appears to be a threshold for object control skill proficiency that children need to reach to enhance their physical activity levels which provides support for a motor skill "proficiency barrier". This provides a tangible benchmark for children to achieve in motor competence programs.
Assuntos
Exercício Físico , Destreza Motora , Criança , Masculino , Feminino , Humanos , Estudos Transversais , Modelos LinearesRESUMO
BACKGROUND: Environmentally sustainable food initiatives accompanying nutrition education, such as the Food Education and Sustainability Training (FEAST) program, have gained traction in school settings. The aim of this trial was to conduct an impact and process evaluation of FEAST, to evaluate its effect on children's fruit and vegetable (F&V) intakes, and secondary outcomes: F&V variety consumed, nutrition knowledge, food preparation/cooking skills, self-efficacy and behaviours, food waste knowledge and behaviours, and food production knowledge. METHODS: FEAST was a 10-week curriculum-aligned program, designed to educate children about healthy eating, food waste, and sustainability, while teaching cooking skills. It was implemented by classroom teachers, face-to-face and online, during COVID-19 school closures, in Australia in 2021. A custom designed survey was used to collect baseline and post-intervention data from students. Generalised linear mixed models (GLMM) estimated group differences in pre-post changes for primary and secondary outcomes. Surveys were also administered to students and teachers to evaluate intervention implementation. RESULTS: Twenty schools participated and self-selected to be either intervention schools (n = 10) or wait-list control (WLC) schools (n = 10). A total of 977, 5th and 6th grade children participated in the trial with a mean age of 11.1 years (SD ± 0.7). The FEAST intervention, compared to WLC, did not result in significant increases in primary outcomes nor secondary outcomes. The process evaluation revealed FEAST was well-received by students and teachers, but COVID-19 school closures hindered implementation fidelity with a less intense program delivered under the constraints of pandemic lockdowns. CONCLUSIONS: This is the first cluster non-randomized controlled trial designed to independently evaluate FEAST in the primary-school setting. No evidence was found for improved F&V intakes in children, nor secondary outcomes. However, the positive process evaluation results suggest that further trials of the program are warranted. If implemented as originally designed (pre-pandemic), with increased duration and complemented by supporting school policies, such programs have the potential to improve children's daily F&V intakes, cooking skills and food waste behaviours. This would support the Australian curriculum and contribute to: health promotion within schools and sustainable schools initiatives, the national agenda to reduce food waste and sustainable development goals. AUSTRALIAN AND NEW ZEALAND CLINICAL TRIALS REGISTRY: [ACTRN12620001347954]- Registered prospectively on 14/12/2020.
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COVID-19 , Eliminação de Resíduos , Criança , Humanos , Alimentos , Austrália , Instituições Acadêmicas , COVID-19/prevenção & controleRESUMO
BACKGROUND: The promotion of healthy eating is a public health priority. Poor dietary behaviours, including low fruit and vegetable (F&V) consumption are of particular concern among children. Novel nutrition promotion strategies are needed to improve F&V consumption. Sustainability education could be used to support nutrition education within the school context. The purpose of this paper is to report the protocol for impact and process evaluation of the school-based Food Education and Sustainability Training (FEAST) program, designed to educate children about sustainability, food waste and nutrition, using hands-on cooking activities. METHODS: A pragmatic, parallel, cluster non-randomized controlled trial with pre- and post-measures, will be implemented among 20 primary schools (10 intervention vs 10 wait-list-control) within NSW, Australia, involving children in Grades 5-6. FEAST is a curriculum-aligned program, delivered as a 1.5-h lesson/week, for a 10-week unit of inquiry, incorporating theory and cooking. FEAST was developed using theoretical frameworks which included Social Cognitive Theory and the Precede-Proceed Planning model. Primary outcomes include children's self-reported F&V intakes (serves/day). Food literacy constructs such as: nutrition knowledge, food preparation and cooking skills, self-efficacy and behaviours, food waste knowledge and behaviours and food production knowledge, will be assessed as secondary outcomes. Process evaluation will assess program reach, adoption, implementation, maintenance, satisfaction and perceived benefits by teachers and students. An online survey (including quantitative and qualitative questions) was developed for administration at baseline (impact evaluation) and immediately post-intervention (impact and process evaluation). Intervention effects on quantitative study outcomes will be estimated with âgeneralised linear mixed models, including random effects and will follow the intention-to-treat principles. Open-ended questions embedded within the surveys will be analysed qualitatively using content and thematic analyses. DISCUSSION: Results from this trial will provide valuable information on the value of adding environmental sustainability strategies to nutrition education in schools. Results will inform the design of future research and programs focused on primary-school children's nutrition, sustainability-related behaviours and experiential school-based interventions. TRIAL REGISTRATION: Trial registered 14th December 2020 with the Australian and New Zealand Clinical Trials Registry ( ACTRN12620001347954 ).
Assuntos
Eliminação de Resíduos , Serviços de Saúde Escolar , Austrália , Criança , Promoção da Saúde , Humanos , Nova Zelândia , Avaliação de Programas e Projetos de Saúde , Instituições AcadêmicasRESUMO
In middle-aged and older men, an 18-month multi-component exercise program improved spinal trabecular BMD, paraspinal, and psoas muscle cross-sectional area (CSA) but not visceral adipose tissue (VAT). However, changes in both muscle and VAT CSA were associated with changes in spinal BMD, independent of the exercise intervention. INTRODUCTION: In older men, we previously reported that a multi-component exercise program improved lumbar spine (LS) trabecular volumetric BMD (Tb.vBMD) compared with no exercise. This study aimed to investigate the following: (1) the effect of the exercise program on paraspinal and psoas (back) muscle CSA and VAT, and 2) if any exercise-related changes in muscle CSA and/or VAT were associated with changes in spinal BMD. METHODS: Men (n = 180) aged 50-79 years were randomized to an exercise or no-exercise group. Exercise involved high-intensity progressive resistance training (60-85% max) with weight-bearing impact exercise (3 days/week) for 18 months. Quantitative computed tomography was used to assess L1-L3 Tb.vBMD, paraspinal, and psoas muscle CSA and VAT. RESULTS: Exercise resulted in a 2.6% ((95% CI, 1.1, 4.1), P < 0.01) net gain in back muscle CSA, but no effect on VAT (-1.6% (95% CI, -7.3, 4.2)) relative to no exercise. Robust regression indicated that percentage changes in Tb.vBMD were positively associated with changes (expressed as z-scores) in back muscle CSA in both the exercise (beta (ß)-coefficient = 1.9, 95% CI 0.5, 3.2, P = 0.007) and no-exercise (ß = 2.6, 95% CI, 1.1, 4.1, P = 0.001) group, and negatively with the changes in VAT (ß = -2.0, 95% CI -3.3, -0.7, P = 0.003) in the exercise only group. There were no group differences in the slopes for the muscle-bone or VAT-bone relationships. Regression analysis (pooled data) revealed that back muscle CSA and VAT were independent predictors of the change in Tb.vBMD, explaining 14% of the variance. CONCLUSION: A multi-component exercise program in middle-aged and older men improved spinal BMD and back muscle size but not visceral fat. However, changes in back muscle size and VAT were associated with the changes in spinal BMD, independent of exercise. TRIAL REGISTRATION: ACTRN 12617001224314, 22/08/2017 retrospectively registered.
Assuntos
Músculos do Dorso , Densidade Óssea , Idoso , Exercício Físico , Terapia por Exercício , Humanos , Gordura Intra-Abdominal/diagnóstico por imagem , Masculino , Pessoa de Meia-IdadeRESUMO
The methionine-folate cycle-dependent one-carbon metabolism is implicated in the pathophysiology of schizophrenia. Since schizophrenia is a developmental disorder, we examined the effects that perturbation of the one-carbon metabolism during gestation has on mice progeny. Pregnant mice were administered methionine equivalent to double their daily intake during the last week of gestation. Their progeny (MET mice) exhibited schizophrenia-like social deficits, cognitive impairments and elevated stereotypy, decreased neurogenesis and synaptic plasticity, and abnormally reduced local excitatory synaptic connections in CA1 neurons. Neural transcript expression of only one gene, encoding the Npas4 transcription factor, was >twofold altered (downregulated) in MET mice; strikingly, similar Npas4 downregulation occurred in the prefrontal cortex of human patients with schizophrenia. Finally, therapeutic actions of typical (haloperidol) and atypical (clozapine) antipsychotics in MET mice mimicked effects in human schizophrenia patients. Our data support the validity of MET mice as a model for schizophrenia, and uncover methionine metabolism as a potential preventive and/or therapeutic target.
Assuntos
Metionina/metabolismo , Esquizofrenia/metabolismo , Animais , Antipsicóticos/uso terapêutico , Fatores de Transcrição Hélice-Alça-Hélice Básicos/efeitos dos fármacos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Região CA1 Hipocampal/efeitos dos fármacos , Clozapina/uso terapêutico , Deficiências do Desenvolvimento/fisiopatologia , Modelos Animais de Doenças , Feminino , Ácido Fólico/metabolismo , Haloperidol/uso terapêutico , Humanos , Masculino , Camundongos , Neurogênese , Plasticidade Neuronal , Transferases de Grupo de Um Carbono/metabolismo , Córtex Pré-Frontal/embriologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Comportamento Estereotipado/efeitos dos fármacos , Tetra-HidrofolatosRESUMO
BACKGROUND: It is important to assess young children's perceived Fundamental Movement Skill (FMS) competence in order to examine the role of perceived FMS competence in motivation toward physical activity. Children's perceptions of motor competence may vary according to the culture/country of origin; therefore, it is also important to measure perceptions in different cultural contexts. The purpose was to assess the face validity, internal consistency, test-retest reliability and construct validity of the 12 FMS items in the Pictorial Scale for Perceived Movement Skill Competence for Young Children (PMSC) in a Portuguese sample. METHODS: Two hundred one Portuguese children (girls, n = 112), 5 to 10 years of age (7.6 ± 1.4), participated. All children completed the PMSC once. Ordinal alpha assessed internal consistency. A random subsamples (n = 47) were reassessed one week later to determine test-retest reliability with Bland-Altman method. Children were asked questions after the second administration to determine face validity. Construct validity was assessed on the whole sample with a Bayesian Structural Equation Modelling (BSEM) approach. The hypothesized theoretical model used the 12 items and two hypothesized factors: object control and locomotor skills. RESULTS: The majority of children correctly identified the skills and could understand most of the pictures. Test-retest reliability analysis was good, with an agreement ration between 0.99 and 1.02. Ordinal alpha values ranged from acceptable (object control 0.73, locomotor 0.68) to good (all FMS 0.81). The hypothesized BSEM model had an adequate fit. CONCLUSIONS: The PMSC can be used to investigate perceptions of children's FMS competence. This instrument can also be satisfactorily used among Portuguese children.
Assuntos
Destreza Motora/fisiologia , Autoavaliação (Psicologia) , Criança , Comportamento Infantil/fisiologia , Comportamento Infantil/psicologia , Desenvolvimento Infantil/fisiologia , Pré-Escolar , Diversidade Cultural , Exercício Físico/fisiologia , Feminino , Humanos , Masculino , Percepção , Portugal , Reprodutibilidade dos Testes , AutoeficáciaRESUMO
OBJECTIVE: This cross-sectional study aimed to identify sociodemographic and behavioural characteristics of 'overweight-resilient' women, that is, women who were in a healthy body weight range, despite living in socioeconomically disadvantaged neighbourhoods that place them at increased risk of obesity. The study also aimed to test a comprehensive theoretically derived model of the associations between intrapersonal, social and environmental factors and obesity among this target group. PARTICIPANTS: A total of 3235 women aged 18-45 years from 80 urban and rural neighbourhoods throughout Victoria, Australia, participated in the Resilience for Eating and Activity Despite Inequality study. MEASUREMENTS: Women reported height, weight, sociodemographic characteristics, leisure-time physical activity, dietary behaviours and a range of theoretically derived cognitive, social and neighbourhood environmental characteristics hypothesized to influence obesity risk. A theoretical model predicting body mass index (BMI) was tested using structural equation models. RESULTS: Women classified as 'resilient' to obesity tended to be younger, born overseas, more highly educated, unmarried and to have higher or undisclosed household incomes. They engaged in more leisure-time physical activity and consumed less fast foods and soft drinks than overweight/obese women. Neighbourhood characteristics, social characteristics and cognitive characteristics all contributed to explaining variation in BMI in the hypothesized directions. CONCLUSIONS: These results demonstrate several characteristics of women appearing 'resilient' to obesity, despite their increased risk conferred by residing in socioeconomically disadvantaged neighbourhoods. Acknowledging the cross-sectional study design, the results advance theoretical frameworks aimed at investigating obesity risk by providing evidence in support of a comprehensive model of direct and indirect effects on obesity of neighbourhood, as well as social, cognitive and behavioural characteristics.
Assuntos
Índice de Massa Corporal , Dieta/estatística & dados numéricos , Comportamentos Relacionados com a Saúde , Obesidade/epidemiologia , Áreas de Pobreza , Fumar/epidemiologia , Populações Vulneráveis/estatística & dados numéricos , Adolescente , Adulto , Estudos Transversais , Escolaridade , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Disparidades nos Níveis de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Características de Residência , Fumar/efeitos adversos , Inquéritos e Questionários , Vitória/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: To investigate sociodemographic and behavioural characteristics associated with weight status among women with children living in socioeconomically disadvantaged neighbourhoods. METHODS AND PROCEDURES: A total of 1680 women aged 18-46 years, living in socioeconomically disadvantaged neighbourhoods with dependent children (aged 0-18 years), provided self-report data on height and weight and a range of sociodemographic and behavioural (for example, dietary intake, physical activity and time spent sitting) characteristics. RESULTS: Half of the women were classified as having a healthy weight (body mass index=18.5-25). Bivariable ordinal logistic regression analyses indicated that a healthy weight status was associated with a range of sociodemographic and behavioural characteristics. In a multivariable model, a healthy weight status among women was associated with being younger and unmarried, speaking a language other than English at home, having a medium or high level of education, and a partner with a high level of education, having a high household income, spending more time engaged in leisure-time physical activity and less time spent sitting, and having a lower consumption of soft drink. DISCUSSION: The present findings highlight that a considerable proportion of women with children living in disadvantaged neighbourhoods manage to maintain a healthy weight. Acknowledging the cross-sectional nature of this study, strategies aimed at helping women with children in socioeconomically disadvantaged areas to maintain their weight should focus on increasing physical activity, and reducing sitting time and soft drink consumption.
Assuntos
Peso Corporal/fisiologia , Atividade Motora/fisiologia , Áreas de Pobreza , Adolescente , Adulto , Estatura , Índice de Massa Corporal , Criança , Pré-Escolar , Estudos Transversais , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Características de Residência , Meio Social , Fatores Socioeconômicos , Inquéritos e Questionários , Adulto JovemRESUMO
MiRP1 (encoded by the KCNE2 gene) is one of a family of five single transmembrane domain voltage-gated potassium (Kv) channel ancillary subunits currently under intense scrutiny to establish their position in channel complexes and elucidate alpha subunit contact points, but its structure is unknown. MiRP1 mutations are associated with inherited and acquired cardiac arrhythmia. Here, synthetic peptides corresponding to human MiRP1 (full-length and separate domains) were structurally analyzed using FTIR and CD spectroscopy. The N-terminal (extracellular) domain was soluble and predominantly non-ordered in aqueous media, but predominantly alpha-helical in L-alpha-lysophosphatidylcholine (LPC) micelles. The MiRP1 transmembrane domain was predominantly a mixture of alpha-helix and non-ordered structure in LPC micelles, with a minor contribution from non-aggregated beta-strand. The intracellular C-terminal domain was insoluble in aqueous solution; reconstitution into non-aqueous environments resulted in solubility and adoption of increasing amounts of alpha-helix, with the solvent order sodium dodecyl sulphate < dimyristoyl L-alpha-phosphatidylcholine (DMPC) < LPC < trifluoroethanol. Correlation of secondary structure changes with lipid transition temperature during heating suggested that the MiRP1 C-terminus incorporates into DMPC bilayers. Full-length MiRP1 was soluble in SDS micelles and calculated to contain 34% alpha-helix, 23% beta-strand and 43% non-ordered structure in this environment, as determined by CD spectroscopy. Thus, MiRP1 is highly dependent upon hydrophobic interaction via lipid and/or protein contacts for adoption of ordered structure without nonspecific aggregation, consistent with a role as a membrane-spanning subunit within Kv channel complexes. These data will provide a structural framework for ongoing mutagenesis-based in situ structure-function studies of MiRP1 and its relatives.
Assuntos
Canais de Potássio de Abertura Dependente da Tensão da Membrana/química , Sequência de Aminoácidos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Bicamadas Lipídicas , Micelas , Dados de Sequência Molecular , Fragmentos de Peptídeos/química , Fosfolipídeos/química , Canais de Potássio de Abertura Dependente da Tensão da Membrana/isolamento & purificação , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Conformação Proteica , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Subunidades Proteicas/químicaRESUMO
This study examined two year changes in children's active transport and independent mobility and prospective associations between individual, social and physical environmental predictors of interest and these behaviors two years later. Overall, 43.5% of children (12.0±2.1 years) used active transport on the school journey at T1 and at T2 (p=0.77), and 35.3% engaged in independent mobility on the school journey at T1 and 29.6% at T2 (p=0.07). Enjoyment, parental safety concerns, and proximity to walking tracks were associated with independent mobility on the school journey. Road safety and social norms were associated with active transport and independent mobility to local destinations. These factors provide potential targets for interventions.
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Áreas de Pobreza , Características de Residência , Segurança , Caminhada , Ciclismo , Transporte Biológico Ativo , Criança , Feminino , Humanos , Mães/psicologia , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
The recombinant N-terminal fragment (amino acids 14-162) of a tetrameric voltage-gated potassium channel (K(V)1.1) has been studied using spectroscopic techniques. Evidence is presented that it forms a tetramer in aqueous solution, whereas when solubilised in 1% Triton X-100 it remains monomeric. The secondary structure content of both monomeric and tetrameric K(V)1.1 N-terminal fragment has been estimated from FTIR and CD spectroscopy to be 20-25% alpha-helix, 20-25% beta-sheet, 20% turns and 30-40% random coil. Solubilisation of the protein in detergent is shown by hydrogen-deuterium exchange analysis to alter tertiary structure rather than secondary structure and this may be the determining factor in tetramerisation ability. Using molecular modelling we propose a supersecondary structure consisting of two structural domains.
Assuntos
Canais de Potássio de Abertura Dependente da Tensão da Membrana , Canais de Potássio/química , Estrutura Secundária de Proteína , Sequência de Aminoácidos , Dicroísmo Circular , Clonagem Molecular , Citoplasma/química , Canal de Potássio Kv1.1 , Dados de Sequência Molecular , Octoxinol , Proteínas Recombinantes/química , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
LINKED ARTICLE: This article is a Commentary on Kisselbach J, Seyler C, Schweizer PA, Gerstberger R, Becker R, Katus HA and Thomas D (2014). Modulation of K2P2.1 and K2P10.1 K+ channel sensitivity to carvedilol by alternative mRNA translation initiation. Br J Pharmacol 171: 5182-5194. doi: 10.1111/bph.12596.
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Accurate quantitation of local glucose metabolic rates (LMRglc) of abnormal tissues such as brain tumors with the 2-deoxyglucose (DG) method requires knowledge of the tissue rate constants and lumped constant. The deoxyglucose rate constants were measured in an experimental intracerebral glioma in 24 awake rats with a dual tracer [(3H)-DG and (14C)-DG] method. Tissue time points were obtained at 2, 5, 10, 18, 30, 60, 90, and 180 min after injection by decapitation and liquid scintillation counting. Blood samples were obtained at 1 min intervals initially and at longer intervals later. The rate constants were estimated with parameter estimation. LMRglc was calculated from the rate constants, assuming a lumped constant of 0.5. K1 for normal cerebrum was found to be 0.258 ml/g/min, and k2-k4 were 0.406, 0.075, and 0.0103 min-1; LMRglc = 65.1 mumol/100 g/min. The corresponding values for the glioma were 0.108, 0.126, 0.040, and 0.0019 with LMRglc = 41.7. The considerably lower k4 in the glioma was reflected in persistent higher activity in the glioma at longer times. Thus, tissue activity alone cannot be used to assess relative glucose metabolic rates in abnormal tissues such as gliomas, particularly at late times after injection.
Assuntos
Neoplasias Encefálicas/metabolismo , Encéfalo/metabolismo , Desoxiaçúcares/metabolismo , Desoxiglucose/metabolismo , Glioma/metabolismo , Animais , Glicemia/metabolismo , Tronco Encefálico/metabolismo , Cerebelo/metabolismo , Cinética , Ratos , Ratos Endogâmicos F344RESUMO
The lumped constant (LC) for calculating the regional glucose (glc) metabolic rate by the deoxyglucose (DG) method was estimated in a transplanted rat glioma and normal rat brain. First, the hexose utilization index (HUI) was measured at 1.5, 3.0, and 4.5 min in right hemisphere glioma implants and uninvolved contralateral hemisphere following bolus intravenous injections of [3H]DG and [14C]glucose. At these times, the glioma HUI values were 0.639, 0.732, and 0.712, respectively, and the coordinate left hemisphere values were 0.432, 0.449, and 0.418. Second, the volumes of distribution of DG and glucose were determined to be 0.436 and 0.235 in glioma implants and 0.402 and 0.237 in left hemisphere, respectively. Third, following simultaneous intracarotid injections of [3H]DG and [14C]glucose, the ratio K1/K1 was 1.1 in glioma grafts and 1.3 in left hemisphere. With these values for HUI, volume of distribution, and K1 ratio, the LC in this rat glioma was estimated to be 2.1 times higher than the left hemisphere LC (p less than 0.02). These results suggest that measurement of brain tumor CMRglc using a normal brain LC may significantly overestimate the true tumor CMRglc.
Assuntos
Astrocitoma/metabolismo , Neoplasias Encefálicas/metabolismo , Encéfalo/metabolismo , Desoxiaçúcares/farmacocinética , Desoxiglucose/farmacocinética , Glucose/metabolismo , Animais , Radioisótopos de Carbono , Cromatografia por Troca Iônica , Feminino , Modelos Biológicos , Transplante de Neoplasias , Ratos , Ratos Endogâmicos F344 , TrítioRESUMO
Intracranial fungal aneurysms arise from major cerebral arteries. Fungi directly invade vessel walls from the luminal surface (fungal emboli) or from the adventitia (fungal meningitis). The vasa vasorum are free of fungi. Aneurysmal rupture is common with extensive hemorrhagic necrosis of the surrounding brain. Aspergillus is the usual causative agent; its sources are nasal sinusitis or endocarditis.
Assuntos
Aneurisma Infectado/etiologia , Aspergilose , Aneurisma Intracraniano/etiologia , Adolescente , Aneurisma Infectado/microbiologia , Aneurisma Infectado/patologia , Aspergilose/patologia , Feminino , Humanos , Aneurisma Intracraniano/microbiologia , Aneurisma Intracraniano/patologia , Sinusite/complicaçõesRESUMO
UNLABELLED: The feasibility of imaging pentose cycle (PC) glucose utilization in human gliomas with PET was explored in two rat glioma models by means of glucose radiolabeled in either the carbon-1 (C-1) or carbon-6 (C-6) position. METHODS: In vitro, monolayers of T-36B-10 glioma, tissue slices of intracerebral glioma grafts or slices of normal brain were fed [1-14C]glucose or [6-14C]glucose, and the generated [14C]CO2 was trapped to quantitate the ratio of [14C]CO2 from 14C-1 versus 14C-6. In vivo, rats bearing grafts of either T-36B-10 or T-C6 rat gliomas at six subcutaneous sites received simultaneous intravenous injections of either [1-11C]glucose and [6-14C]glucose, or [1-14C]glucose and [6-11C]glucose. Tumors were excised between 5 and 55 min postinjection to quantify tracer uptake while arterial plasma was collected to derive time-activity input curves. RESULTS: In vitro, the C-1/C-6 ratio for CO2 production from T-36B-10 monolayers was 8.8 +/- 0.4 (s.d.), in glioma slices it was 6.1 +/- 2.1 and in normal brain slices it was 1.1 +/- 0.7. PC metabolism in T-36B-10 was 1.8% +/- 0.5 of total glucose utilization. In vivo, tumor radioactivity levels normalized by plasma isotopic glucose levels showed that retained C-1 relative to C-6 radiolabeled glucose was significantly lower in both gliomas, 4.9% lower in T-36B-10 (p < 0.01) and 4.7% lower in T-C6 (p < 0.01). In an additional group of rats bearing T-36B-10 gliomas and exposed to 10 Gy of 137Cs irradiation 4 hr before isotope injection, the C-1 level was 5.6% lower than that for C-6 (p < 0.05). These results were analyzed with a model of glucose metabolism that simultaneously optimized parameters for C-1 and C-6 glucose kinetics by simulating the C-1 and C-6 tumor time-activity curves. The rate constant for loss of radiolabeled carbon from the tumors, k4, was higher for C-1 than for C-6 in all groups of rats (19% higher for T-36B-10 unirradiated, 32% for T-36B-10 irradiated and 32% for T-C6 unirradiated). CONCLUSION: Mathematical modeling, Monte Carlo simulations and construction of receiver-operator-characteristic curves show that if human gliomas have a similar fractional use of the PC, it should be measurable with PET using sequential studies with [1-11C]glucose and [6-11C]glucose.
Assuntos
Neoplasias Encefálicas/metabolismo , Glioma/metabolismo , Glucose/metabolismo , Via de Pentose Fosfato , Tomografia Computadorizada de Emissão , Animais , Neoplasias Encefálicas/diagnóstico por imagem , Radioisótopos de Carbono , Curva ROC , Ratos , Ratos Endogâmicos F344 , Ratos Endogâmicos WF , Células Tumorais Cultivadas/metabolismoRESUMO
Complex segregation analysis was applied to data from 88 families containing at least one person with vesicoureteric reflux. Analysis showed that a single major locus was the most important causal factor in this condition, with the mutant allele being dominant to the normal allele and having a gene frequency of about 0.16%. Forty-five percent of gene carriers will have vesicoureteric reflux and/or reflux nephropathy as adults and 15% will develop renal failure, compared to 0.05% and 0.001%, respectively, for those not carrying the gene. This analysis confirms the importance of screening close relatives of persons with proven vesicoureteric reflux or reflux nephropathy.
Assuntos
Genes Dominantes , Refluxo Vesicoureteral/genética , Adolescente , Adulto , Alelos , Criança , Pré-Escolar , Mapeamento Cromossômico , Feminino , Frequência do Gene , Testes Genéticos , Heterozigoto , Humanos , Falência Renal Crônica/genética , Masculino , Mutação , Linhagem , Pielonefrite/genética , RiscoRESUMO
Blood flow changes in response to 20 Gy 137Cs whole brain irradiation were measured with quantitative autoradiography of [14C]iodoantipyrine (IAP) in intracerebral grafts of the 36B-10 rat glioma, the brain around tumor (BAT), the contralateral corpus callosum, and the contralateral cerebral cortex. Irradiations were delivered on Day 14 post-transplantation, and measurements of flow (F) were performed with IAP on Day 15 or Day 16. Mean values of F were determined in individual tumors and in treatment groups. In 15- and 16-day-old unirradiated control tumors, the group mean F was 0.31 ml.g-1.min-1. In both 15- and 16-day-old tumor groups irradiated on Day 14 (Day 1 and 2 postirradiation tumors) the mean F for each day's group was 0.52 ml.g-1.min-1, 68% higher than the control (P less than 0.01). Flow in the BAT and the contralateral corpus callosum similarly was increased at these times (P less than 0.01). Flow in the contralateral cerebral cortex was 1.1, 1.5, and 1.3 ml.g-1.min-1 in the control, 1 day postirradiated, and 2 day postirradiated groups, respectively, but these increases were not significantly different from the control. These data indicate that flow increases in the intracerebral gliomas as well as in normal brain regions during the 2 days following 20 Gy irradiation. Changes such as these following radiotherapy may have important effects on the bioavailability of chemotherapeutic drugs.
Assuntos
Neoplasias Encefálicas/radioterapia , Circulação Cerebrovascular/efeitos da radiação , Glioma/radioterapia , Animais , Velocidade do Fluxo Sanguíneo , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Neoplasias Encefálicas/irrigação sanguínea , Neoplasias Encefálicas/patologia , Radioisótopos de Césio/uso terapêutico , Glioma/irrigação sanguínea , Glioma/patologia , Ratos , Ratos Endogâmicos F344RESUMO
To assess vascular permeability in intracerebral grafts of the 36B-10, F-344 rat glioma following 20 Gy 137Cs whole brain irradiation, the blood-to-tissue transport constant, K, of [14C]-alpha-aminoisobutyric acid (AIB) was measured with quantitative autoradiography. Mean, 90th percentile, and 95th percentile values of K were determined in individual tumors and in treatment groups. In 15-day-old unirradiated control tumors, mean, 90th percentile, and 95th percentile values of K were, respectively, 11.3, 18.4, and 20.8 ml kg-1 min-1. In 15-day-old tumors irradiated on Day 14 (Day 1 postirradiation tumors) the K values were 5.9, 9.4, and 10.4, all of which were significantly less than the respective control values (P less than 0.01). In 16-day-old tumors irradiated on Day 14 (Day 2 postirradiation tumors), the K values were 10.8, 15.0, and 16.0, respectively, none of which was significantly different from control tumors. Mean K values for Day 2 vs Day 1 postirradiation tumors (10.8 vs 5.9) yielded P less than 0.05, but the 90th percentile and 95th percentile values for Day 2 vs Day 1 yielded 0.05 less than P less than 0.10. Separate experiments measured AIB and 86RbCl uptake in 36B-10 cells in vitro 1 and 2 days following 20 Gy irradiation to assess whether this radiation dose reduced the capacity of tumor cells to trap AIB or Rb+. Irradiation did not reduce the accumulation of either tracer, but rather was associated with an increased accumulation of AIB. Therefore, the AIB transport data suggest that vascular permeability and/or surface area decreases significantly in the day following 20 Gy irradiation and that this decrease reverses by the second day following irradiation.
Assuntos
Astrocitoma/radioterapia , Barreira Hematoencefálica/efeitos da radiação , Neoplasias Encefálicas/radioterapia , Ácidos Aminoisobutíricos/metabolismo , Animais , Astrocitoma/irrigação sanguínea , Autorradiografia , Neoplasias Encefálicas/irrigação sanguínea , Permeabilidade Capilar/efeitos da radiação , Radioisótopos de Césio/uso terapêutico , Cinética , Transplante de Neoplasias , Volume Plasmático/efeitos da radiação , Ratos , Ratos Endogâmicos F344 , Rubídio/metabolismoRESUMO
Fully automated microparticle enzyme immunoassays (MEIA) for the IMx immunoassay analyser were developed to detect IgG and IgM antibodies to Toxoplasma gondii. The IgG MEIA results are expressed in International Units (IU) of IgG antibody interpolated from a six point calibration curve covering the range from 0 to 300 IU/ml. Reproducible results were obtained from a calibration curve stored in the instrument for at least one month. The qualitative IgM MEIA expresses results as an index using a single calibrator included in each run. The Toxo IgG MEIA and Toxo IgM MEIA were in 98% and 97% agreement, respectively, with the reference assays used. Twenty four sera can be completely processed in about 35 minutes.