RESUMO
The Dietary Approaches to Stop Hypertension (DASH) eating pattern has been shown to reduce blood pressure (BP) in previous clinical trials. In the PREMIER study, an established behavioural intervention, with or without DASH, promoted greater weight loss than an advice-only control group, but effects of the DASH intervention on BP were weaker. In these analyses, PREMIER data were used to evaluate whether change in dairy product or fruit and vegetable (FV) intake during the first six intervention months impacted changes in weight and/or BP. Study participants were classified as having low or high intakes of dairy products (<1·5 v. ≥1·5 servings/d) and FV (<5 v. ≥5 servings/d) at baseline and 6 months. For dairy products, in particular, participants with higher baseline intakes tended to decrease their intakes during the intervention. In these analyses, subjects consuming <1·5 dairy servings/d at baseline whose intake increased during the intervention lost more weight than those whose intake decreased or remained low throughout (10·6 v. 7·0 pounds (4·8 v. 3·2 kg) lost, respectively, P = 0·002). The same was true for FV intake (11·0 v. 5·9 pounds (5·0 v. 2·7 kg) lost, P < 0·001). We also found synergistic effects of dairy products and FV on weight loss and BP reduction. Specifically, subjects who increased their intakes of dairy products and also consumed ≥5 servings of FV/d lost more weight and had greater reductions in BP than other groups; in addition, higher FV intakes had the greatest benefit to BP among those consuming more dairy products. These results provide evidence that the DASH pattern was most beneficial to individuals whose baseline diet was less consistent with DASH.
Assuntos
Dieta , Abordagens Dietéticas para Conter a Hipertensão , Comportamentos Relacionados com a Saúde , Hipertensão/dietoterapia , Estilo de Vida , Adulto , Pressão Sanguínea , Feminino , Humanos , Hipertensão/prevenção & controle , Masculino , Pessoa de Meia-IdadeRESUMO
This paper reviews the use of descriptive statistics to describe the participants included in a study. It discusses the practicalities of incorporating statistics in papers for publication in Age and Aging, concisely and in ways that are easy for readers to understand and interpret.
Assuntos
Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Projetos de Pesquisa/estatística & dados numéricos , Sujeitos da Pesquisa/estatística & dados numéricos , Interpretação Estatística de Dados , Políticas Editoriais , Guias como Assunto , Humanos , Modelos Estatísticos , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Seleção de Pacientes , Publicações Periódicas como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto/métodosRESUMO
OBJECTIVE: To determine the feasibility of a Dance Centre delivering a programme of mixed dances to people with Parkinson's and identify suitable outcomes for a future definitive trial. DESIGN: A two-group randomized controlled feasibility trial. METHODS: People with Parkinson's were randomized to a control or experimental group (ratio 15:35), alongside usual care. In addition, participants in the experimental group danced with a partner for one hour, twice-a-week for 10 weeks; professional dance teachers led the classes and field-notes were kept. Control-group participants were given dance class vouchers at the end of the study. Blinded assessments of balance, mobility and function were completed in the home. Qualitative interviews were conducted with a subsample to explore the acceptability of dance. RESULTS: A total of 51 people with Parkinson's (25 male) with Hoehn and Yahr scores of 1-3 and mean age of 71 years (range 49-85 years), were recruited to the study. Dance partners were of similar age (mean 68, range 56-91 years). Feasibility findings focused on recruitment (target achieved); retention (five people dropped out of dancing); outcome measures (three measures were considered feasible, changes were recommended). Proposed sample size for a Phase III trial, based on the 6-minute walk test at six months was 220. Participants described dance as extremely enjoyable and the instructors were skilled in instilling confidence and motivation. The main organizational challenges for a future trial were transport and identifying suitable dance partners. CONCLUSION: We have demonstrated the feasibility of conducting the study through a Dance Centre and recommend a Phase III trial.
Assuntos
Dançaterapia , Doença de Parkinson/reabilitação , Acidentes por Quedas/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Humanos , Relações Interpessoais , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/fisiopatologia , Equilíbrio Postural/fisiologia , Teste de CaminhadaRESUMO
Lipolysis in fat tissue represents a major source of circulating fatty acids. Previously, we have found that lipolysis in adipocytes is controlled by early growth response transcription factor Egr1 that directly inhibits transcription of adipose triglyceride lipase, ATGL (Chakrabarti, P., Kim, J. Y., Singh, M., Shin, Y. K., Kim, J., Kumbrink, J., Wu, Y., Lee, M. J., Kirsch, K. H., Fried, S. K., and Kandror, K. V. (2013) Mol. Cell. Biol. 33, 3659-3666). Here we demonstrate that knockdown of the lipid droplet protein FSP27 (a.k.a. CIDEC) in human adipocytes increases expression of ATGL at the level of transcription, whereas overexpression of FSP27 has the opposite effect. FSP27 suppresses the activity of the ATGL promoter in vitro, and the proximal Egr1 binding site is responsible for this effect. FSP27 co-immunoprecipitates with Egr1 and increases its association with and inhibition of the ATGL promoter. Knockdown of Egr1 attenuates the inhibitory effect of FSP27. These results provide a new model of transcriptional regulation of ATGL.
Assuntos
Adipócitos/metabolismo , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Lipase/metabolismo , Proteínas/metabolismo , Células 3T3-L1 , Adipócitos/citologia , Animais , Proteínas Reguladoras de Apoptose , Sítios de Ligação/genética , Células Cultivadas , Proteína 1 de Resposta de Crescimento Precoce/genética , Expressão Gênica , Células HEK293 , Humanos , Immunoblotting , Lipase/genética , Lipólise/genética , Camundongos , Microscopia Confocal , Mutagênese Sítio-Dirigida , Regiões Promotoras Genéticas/genética , Ligação Proteica , Proteínas/genética , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Some consider potatoes to be unhealthy vegetables that may contribute to adverse cardiometabolic health outcomes. We evaluated the association between potato consumption (including fried and non-fried types) and three key cardiometabolic outcomes among middle-aged and older adults in the Framingham Offspring Study. We included 2523 subjects ≥30 years of age with available dietary data from 3-d food records. Cox-proportional hazards models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for hypertension, type 2 diabetes or impaired fasting glucose (T2DM/IFG), and elevated triglycerides, adjusting for anthropometric, demographic and lifestyle factors. In the present study, 36 % of potatoes consumed were baked, 28 % fried, 14 % mashed, 9 % boiled and the rest cooked in other ways. Overall, higher total potato intake (≥4 v. <1 cup-equivalents/week) was not associated with risks of T2DM/IFG (HR 0â 97, 95 % CI 0â 81, 1â 15), hypertension (HR 0â 95; 95 % CI 0â 80, 1â 12) or elevated triglycerides (HR 0â 99, 95 % CI 0â 86, 1â 13). Stratified analyses were used to evaluate effect modification by physical activity levels and red meat consumption, and in those analyses, there were no adverse effects of potato intake. However, when combined with higher levels of physical activity, greater consumption of fried potatoes was associated with a 24 % lower risk (95 % CI 0â 60, 0â 96) of T2DM/IFG, and in combination with lower red meat consumption, higher fried potato intake was associated with a 26 % lower risk (95 % CI 0â 56, 0â 99) of elevated triglycerides. In this prospective cohort, there was no adverse association between fried or non-fried potato consumption and risks of T2DM/IFG, hypertension or elevated triglycerides.
Assuntos
Diabetes Mellitus Tipo 2 , Hipertensão , Solanum tuberosum , Idoso , Diabetes Mellitus Tipo 2/epidemiologia , Glucose , Humanos , Hipertensão/epidemiologia , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Estudos Prospectivos , Solanum tuberosum/efeitos adversos , TriglicerídeosRESUMO
The oxygen uptake efficiency slope is a measure of cardiopulmonary fitness, that can be obtained from a sub-maximal cardiopulmonary exercise test. It has been evaluated in medical patients but its reliability in surgical populations remains uncertain. We conducted a test-retest study with the aim of establishing the reliability of the oxygen uptake efficiency slope in relation to that of the anaerobic threshold and peak oxygen uptake, in general surgical patients. Twenty-six patients over 60 years old completed two symptom-limited, incremental cycle ergometry tests within 7 days. The mean (SD) anaerobic threshold was 13.0 (3.0) mlO(2) .kg(-1) .min(-1) . There were no significant differences between mean test and retest values of anaerobic threshold (p = 0.50), peak oxygen uptake (p = 0.76) or oxygen uptake efficiency slope (p = 0.42). Reliability coefficients (95% CI) for the anaerobic threshold, oxygen uptake efficiency slope and peak oxygen uptake were 66.7% (45.3-87.9%), 89.0% (81.0-96.9%) and 91.7% (85.7-97.8%), respectively. The oxygen uptake efficiency slope was determined easily in all patients and found to have excellent reliability. Its clinical utility in determining pre-operative fitness warrants further evaluation.
Assuntos
Consumo de Oxigênio/fisiologia , Cuidados Pré-Operatórios/métodos , Adolescente , Adulto , Limiar Anaeróbio/fisiologia , Teste de Esforço/métodos , Humanos , Pessoa de Meia-Idade , Prognóstico , Reprodutibilidade dos Testes , Mecânica Respiratória/fisiologia , Adulto JovemRESUMO
We explored the dose-response relations of sodium, potassium, magnesium and calcium with cardiovascular disease (CVD) risk in the Framingham Offspring Study, as well as the combined effects of these minerals. Analyses included 2362 30-64 year-old men and women free of CVD at baseline. Cox proportional-hazards models were used estimate adjusted hazard ratios (HR) and 95% confidence intervals (CIs) for mineral intakes and incident CVD. Cox models with restricted cubic spline functions were used to examine dose-response relations, adjusting for confounding by age, sex, body mass index, dietary fiber intake, and time-varying occurrence of hypertension. Lower sodium intake (<2500 vs. ≥3500 mg/d) was not associated with a lower risk of CVD. In contrast, potassium intake ≥3000 (vs. <2500) mg/d was associated with a 25% lower risk (95% CI: 0.59, 0.95), while magnesium intake ≥320 (vs. <240) mg/d led to a 34% lower risk (95% CI: 0.51, 0.87) of CVD. Calcium intake ≥700 (vs. <500) mg/d was associated with a non-statistically significant 19% lower risk. Restricted cubic spline curves showed inverse dose-response relations of potassium and magnesium with CVD risk, but no such associations were observed for sodium or calcium. These results highlight the importance of potassium and magnesium to cardiovascular health.
Assuntos
Doenças Cardiovasculares/epidemiologia , Dieta , Fatores de Risco de Doenças Cardíacas , Magnésio/administração & dosagem , Potássio na Dieta , Sódio na Dieta , Adulto , Cálcio da Dieta , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos ProporcionaisRESUMO
BACKGROUND & AIMS: Protein intake has been shown to lower risk of aging-related functional decline. The goal of this study was to assess long-term effects of weight-adjusted animal (AP) and plant protein (PP) intakes on aging-related change in functional status and grip strength. METHODS: Framingham Offspring Study participants (n = 1896, 891 men and 1005 women), ≥age 50, were followed for an average of 14.4 years. Protein intake derived from two sets of 3-day diet records (exams 3 and 5) was expressed as both weight-adjusted intake (from residuals) and per kilogram of body weight (g/kg/d). Seven tasks from two standardized assessments (Nagi and the Rosow-Breslau scales) were selected to determine functional status at exams 5-9. Functional impairment was defined as failure to complete (or having a lot of difficulty completing) a given task. Grip strength was assessed by dynamometer at exams 7-9. RESULTS: Participants with higher (vs. lower) weight-adjusted intakes of AP and PP maintained higher functional scores (p = 0.001 and p < 0.001, respectively). After accounting for baseline skeletal muscle mass (SMM) and physical activity, only AP was linked with lower risks of functional impairment. Higher AP intake among sedentary individuals led to 29% (95% CI: 0.51-1.00) reduced risks of impairment; among subjects with lower SMM, higher AP was associated with 30% (95% CI: 0.49-0.98) reduced risks. Physical activity and SMM were independently associated with reduced risks of functional impairment, regardless of protein intake. Finally, higher AP intake led to 34% and 48% greater preservation of grip strength in men (p = 0.012) and women (p = 0.034). Results were similar for protein intake expressed as g/kg/d. CONCLUSIONS: Higher AP intake and higher levels of physical activity and SMM were independently associated with lower risks of functional impairment and greater preservation of grip strength in adults over the age of 50 years.
Assuntos
Proteínas Animais da Dieta/administração & dosagem , Dieta/métodos , Idoso Fragilizado , Fragilidade/prevenção & controle , Sarcopenia/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Dieta/efeitos adversos , Inquéritos sobre Dietas , Exercício Físico , Feminino , Fragilidade/etiologia , Estado Funcional , Avaliação Geriátrica , Força da Mão , Humanos , Masculino , Pessoa de Meia-Idade , Dinamômetro de Força Muscular , Proteínas de Vegetais Comestíveis/administração & dosagem , Fatores de Risco , Sarcopenia/etiologiaRESUMO
THE EXPERIMENTS PRESENTED HERE UTILIZE A HUMAN SERUM MARKEDLY DEFICIENT IN HEMOLYTIC COMPLEMENT ACTIVITY TO SHOW THAT: (a) The hemolytic deficiency is the result of a selective deficiency in hemolytic C1. (b) The relative absence of hemolytic C1 is due to a profound deficit in C1r function associated with less than normal C1s protein and hemolytic function and normal C1q protein concentration and function. This deficit in C1r in the face of normal C1q suggests that different cell types are responsible for the synthesis of each of these components. (c) Whatever the basis for the deficiency of C1r function, this defect results in an inadequate association of the remaining C1 subcomponents, C1q and C1s, even in the presence of calcium ions, thus suggesting that C1r has an important role in the assembly and/or maintenance of macromolecular C1.
Assuntos
Proteínas do Sistema Complemento/metabolismo , Hemólise , Adolescente , Animais , Cromatografia DEAE-Celulose , Proteínas do Sistema Complemento/análise , Proteínas do Sistema Complemento/biossíntese , Proteínas do Sistema Complemento/isolamento & purificação , Glomerulonefrite/imunologia , Cobaias , Humanos , Soros Imunes , Imunodifusão , Ovinos , UltracentrifugaçãoRESUMO
Bacterial lipopolysaccharides (LPS) derived from a variety of organisms effectively induced C consumption in humans, bovines, and porcines with developmental agammaglobulinemia; birds with experimental agammaglobulinemia; and humans with agammaglobulinemia syndromes. This interaction proceeded even in precolostral piglet sera which contained less than 2.5 x 10(-6) mg/ml gamma globulin, and led to generation of neutrophil chemotactic factor and anaphylatoxin in these sera. Hence, the LPS-C interaction can proceed in sera markedly deficient in immunoglobulin. The question of whether immunoglobulins can be bypassed in the LPS-C interaction, or whether they are regularly utilized in a way so efficient that their participation is masked, was considered.
Assuntos
Agamaglobulinemia/imunologia , Reações Antígeno-Anticorpo , Proteínas do Sistema Complemento/metabolismo , Lipopolissacarídeos/metabolismo , Agamaglobulinemia/metabolismo , Animais , Formação de Anticorpos , Bovinos , Galinhas , Testes de Fixação de Complemento , Proteínas do Sistema Complemento/análise , Proteínas Hemolisinas/análise , Humanos , Recém-Nascido , Testes de Neutralização , Coelhos , Serratia/imunologia , Ovinos , Suínos , Peçonhas/isolamento & purificação , gama-Globulinas/análiseRESUMO
Interspecific hybrids between the related wild barley species Hordeum marinum and H. bulbosum were generated and tested regarding their chromosomal stability and chromatin properties. Unlike in H. vulgare x H. bulbosum hybrid embryos, there was no effect of temperature on uniparental chromosome elimination or retention during hybrid seed development and 7 chromosomes from each parent were detected according to genomic in situ hybridization analyses. The centromere-specific histone H3 gene (CENH3) of both parental genomes is active in hybrid plants. Indirect immunostaining of flow-sorted 2C nuclei indicated that no major reorganization of histone H3 methylation (K4, K9 and K27), H3K9 acetylation and histone H2A ubiquitination marks or location of active RNA polymerase II sites occurred after interspecific hybridization.
Assuntos
Cromatina/genética , Cromossomos de Plantas/genética , Hordeum/genética , Sequência de Aminoácidos , Sequência de Bases , Centrômero/genética , Centrômero/metabolismo , Cromatina/metabolismo , Pareamento Cromossômico/genética , Cromossomos de Plantas/metabolismo , Primers do DNA/genética , DNA de Plantas/genética , Epigênese Genética , Genes de Plantas , Instabilidade Genômica , Histonas/genética , Histonas/metabolismo , Hordeum/classificação , Hordeum/citologia , Hordeum/metabolismo , Hibridização Genética , Hibridização in Situ Fluorescente , Mitose/genética , Dados de Sequência Molecular , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , RNA Polimerase II/metabolismo , Homologia de Sequência de Aminoácidos , Especificidade da EspécieRESUMO
The objective of this study was to present nationally representative findings on sociodemographic and psychopathologic predictors of first incidence of Diagnostic and Statistical Manual of Mental Disorders, 4th edn (DSM-IV) substance, mood and anxiety disorders using the Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions. One-year incidence rates of DSM-IV substance, mood and anxiety disorders were highest for alcohol abuse (1.02), alcohol dependence (1.70), major depressive disorder (MDD; 1.51) and generalized anxiety disorder (GAD; 1.12). Incidence rates were significantly greater (P<0.01) among men for substance use disorders and greater among women for mood and anxiety disorders except bipolar disorders and social phobia. Age was inversely related to all disorders. Black individuals were at decreased risk of incident alcohol abuse and Hispanic individuals were at decreased risk of GAD. Anxiety disorders at baseline more often predicted incidence of other anxiety disorders than mood disorders. Reciprocal temporal relationships were found between alcohol abuse and dependence, MDD and GAD, and GAD and panic disorder. Borderline and schizotypal personality disorders predicted most incident disorders. Incidence rates of substance, mood and anxiety disorders were comparable to or greater than rates of lung cancer, stroke and cardiovascular disease. The greater incidence of all disorders in the youngest cohort underscores the need for increased vigilance in identifying and treating these disorders among young adults. Strong common factors and unique factors appear to underlie associations between alcohol abuse and dependence, MDD and GAD, and GAD and panic disorder. The major results of this study are discussed with regard to prevention and treatment implications.
Assuntos
Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/psicologia , Transtornos do Humor/epidemiologia , Transtornos do Humor/psicologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Adulto , Alcoolismo , Transtornos de Ansiedade/diagnóstico , Demografia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Inquéritos Epidemiológicos , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/diagnóstico , Escalas de Graduação Psiquiátrica , Psicopatologia , Estudos Retrospectivos , Transtornos Relacionados ao Uso de Substâncias/classificação , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Adulto JovemRESUMO
BACKGROUND: Sensorimotor impairment in neck pain sufferers is well established. Recent research has identified impairment in head and trunk co-ordination in this population. Presently, no clinically appropriate testing exists to quantify such impairment. OBJECTIVE: To determine if a simple and clinically relevant test of head-trunk co-ordination can identify dysfunction in neck pain subjects when compared to healthy controls. STUDY DESIGN: Cross-sectional observational study. METHODS: Thirty-one neck pain and 29 healthy control subjects were assessed using head- and chest-mounted lasers with a target positioned 90 cm away. Subjects were required to rotate the trunk at least 45° with the head laser to be kept as accurately as possible in the centre of the target while sitting and standing. Maximal deviation of the head to the left and right of the target's centre with each trunk movement was measured. RESULTS: The neck pain group demonstrated significantly greater head deviation from the centre in all but one test direction (p= <0.03). Head deviation to the same side as trunk rotation was larger in the neck pain group for both sitting and standing (p= <0.01). No significant differences existed between testing in sitting and standing. CONCLUSION: Differences in trunk-head control exist in persons suffering from neck pain compared to healthy individuals, which can be demonstrated using simple equipment suggesting clinical utility of the measure. Performing the task in standing would seem most suitable as it can avoid influence by reduced thoracic mobility. Further research is required to establish the clinical suitability of this test.
Assuntos
Cervicalgia , Propriocepção , Ataxia , Estudos Transversais , Humanos , Cervicalgia/diagnóstico , TroncoRESUMO
UNLABELLED: In inoperable malignancy, pain relief with opioids is often inadequate. Nerve block procedures may improve symptom control. Our aim was to assess celiac plexus block (CPB) and thoracoscopic splanchnicectomy (TS) in patients receiving appropriate medical management (MM). METHODS: Patients with confirmed irresectable malignancy of the pancreas or upper abdominal viscera who required opioid analgesia were randomized to MM alone, MM+CPB, or MM+TS. Randomization was stratified by treatment centre, tumour type and previous opioid medication. The primary endpoint was pain relief at 2 months. RESULTS: 65 patients (58 pancreas cancer) were randomized, 18 withdrew or died within 2 months. Effective pain relief was achieved in only one third of subjects at 2 weeks, and just under half at 2 months (MM: 6/19 and 5/12 evaluable patients; CPB: 5/14 and 5/9; TS 4/14 and 4/11). There were no significant differences between the groups in pain scores or opioid consumption, and there was no correlation between continued use of opioids and effective pain relief. DISCUSSION: Previous randomized studies have shown small differences in pain scores, but no difference in opioid consumption and quality of life. The absence of any benefit from interventions in the present study questions their value.
Assuntos
Analgésicos Opioides/uso terapêutico , Plexo Celíaco/cirurgia , Bloqueio Nervoso , Manejo da Dor , Neoplasias Pancreáticas/complicações , Nervos Esplâncnicos/cirurgia , Idoso , Plexo Celíaco/efeitos dos fármacos , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Dor/etiologia , Dor/cirurgia , Resultado do TratamentoRESUMO
We found that several normal samples of aggregated gamma globulin consistently fixed essentially equal amounts of guinea pig complement, while samples of gamma globulin from three of four hypogammaglobulinemic patients were markedly deficient in this biologic function. Thus, the previously observed limited heterogeneity of gamma globulin in patients with hypogammaglobulinemia is also associated with inefficiency in at least one biological function.
Assuntos
Agamaglobulinemia , Proteínas do Sistema Complemento , gama-Globulinas , Animais , Fenômenos Químicos , Química , Cobaias , Humanos , Técnicas In VitroRESUMO
A major feature of Alzheimer's disease is the accumulation of amyloid-beta peptide (Abeta) in the brain both in the form of plaques in the cerebral cortex and in blood vessel as cerebral amyloid angiopathy (CAA). Experimental models and human clinical trials have shown that accumulation of Abeta plaques can be reversed by immunotherapy. In this study, we hypothesized that Abeta in plaques is solubilized by antibodies generated by immunization and drains via the perivascular pathway, detectable as an increase in cerebrovascular Abeta. We have performed a follow up study of Alzheimer's disease patients immunized against Abeta42. Neuropathological examination was performed on nine patients who died between four months and five years after their first immunization. Immunostaining for Abeta40 and Abeta42 was quantified and compared with that in unimmunized Alzheimer's disease controls (n = 11). Overall, compared with these controls, the group of immunized patients had approximately 14 times as many blood vessels containing Abeta42 in the cerebral cortex (P<0.001) and seven times more in the leptomeninges (P = 0.013); among the affected blood vessels in the immunized cases, most of them had full thickness and full circumference involvement of the vessel wall in the cortex (P = 0.001), and in the leptomeninges (P = 0.015). There was also a significantly higher level of cerebrovascular Abeta40 in the immunized cases than in the unimmunized cases (cortex: P = 0.009 and leptomeninges: P = 0.002). In addition, the immunized patients showed a higher density of cortical microhaemorrhages and microvascular lesions than the unimmunized controls, though none had major CAA-related intracerebral haemorrhages. The changes in cerebral vascular Abeta load did not appear to substantially influence the structural proteins of the blood vessels. Unlike most of the immunized patients, two of the longest survivors, four to five years after first immunization, had virtually complete absence of both plaques and CAA, raising the possibility that, given time, Abeta is eventually cleared from the cerebral vasculature. The findings are consistent with the hypothesis that Abeta immunization results in solubilization of plaque Abeta42 which, at least in part, exits the brain via the perivascular pathway, causing a transient increase in the severity of CAA. The extent to which these vascular alterations following Abeta immunization in Alzheimer's disease are reflected in changes in cognitive function remains to be determined.
Assuntos
Doença de Alzheimer/terapia , Vacinas contra Alzheimer/uso terapêutico , Peptídeos beta-Amiloides/imunologia , Angiopatia Amiloide Cerebral/terapia , Fragmentos de Peptídeos/imunologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Vasos Sanguíneos/metabolismo , Angiopatia Amiloide Cerebral/metabolismo , Angiopatia Amiloide Cerebral/patologia , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/metabolismo , Hemorragia Cerebral/etiologia , Feminino , Seguimentos , Humanos , Imunoterapia Ativa/métodos , Masculino , Meninges/irrigação sanguínea , Meninges/metabolismo , Pessoa de Meia-Idade , Fragmentos de Peptídeos/metabolismo , SolubilidadeRESUMO
Stem rust, caused by Puccinia graminis f. sp. tritici, is an important disease on barley (Hordeum vulgare). Host resistance has effectively controlled stem rust, primarily through use of gene Rpg1. However, virulence to Rpg1 is present in North America, and a new race (TTKSK, or Ug99) from eastern Africa threatens barley production. A search for novel resistance was previously conducted, and an interspecific barley breeding line (212Y1) with introgressed chromatin from H. bulbosum was identified as carrying resistance to races MCCF and QCCJ. This study evaluated the inheritance of resistance in 212Y1 using populations from crosses to Morex (Rpg1 donor) and Q21861 (rpg4 donor) and the pathogen races MCCF (avirulent on Rpg1 and rpg4) and QCCJ (virulent on Rpg1 and avirulent on rpg4), and determined the chromosomal position of the introgression using genomic in situ hybridization (GISH) and chromosome-specific polymerase chain reaction (PCR)-based markers. Progeny from the 212Y1/Q21861 F(2) population segregated for resistant and susceptible plants, indicating different gene loci. Genetic analyses of Morex/212Y1 F(3) families fit a 7 homozygous resistant (HR):8 segregating:1 homozygous susceptible (HS) family segregation ratio to race MCCF, indicating that two genes controlled resistance. Plants in segregating families were in 3R:1S (Rpg1), 13R:3S (Rpg1+212Y1), and 1R:3S (212Y1) ratios. Genetic analyses of the same F(3) families fit a 1HR:2 segregating:1HS family segregation ratio to race QCCJ, indicating monogenic inheritance. Plants in segregating families were in a 1R: 3S ratio, indicating recessive inheritance in 212Y1. The introgression from H. bulbosum into H. vulgare was positioned on chromosome 6HS based on GISH and the PCR-based markers. No known stem rust resistance gene has previously been mapped to that region. Thus, it is proposed to name this novel gene from H. bulbosum as rpg6.
Assuntos
Basidiomycota/fisiologia , Mapeamento Cromossômico , Hordeum/genética , Cromossomos de Plantas/genética , Genes de Plantas , Teste de Complementação Genética , Hordeum/imunologia , Hordeum/microbiologia , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Hibridização Genética , Padrões de Herança , Doenças das Plantas/genética , Doenças das Plantas/imunologiaRESUMO
Visceral obesity is associated with insulin resistance and higher risk of type 2 diabetes and metabolic diseases. A limited ability of adipose tissues to remodel through the recruitment and differentiation of adipose stem cells (ASCs) is associated with adipose tissue inflammation and fibrosis and the metabolic syndrome. We show that the lower adipogenesis of omental (Om) compared with abdominal subcutaneous (Abdsc) ASCs was associated with greater secretion of TGFß ligands that acted in an autocrine/paracrine loop to activate SMAD2 and suppress adipogenesis. Inhibition of TGFß signaling rescued Om ASC differentiation. In Abdsc ASCs, low concentrations of dexamethasone suppressed TGFß signaling and enhanced adipogenesis, at least in part by increasing TGFBR3 protein that can sequester TGFß ligands. Om ASCs were resistant to these dexamethasone effects; recombinant TGFBR3 increased their differentiation. Pericellular fibrosis, a hallmark of dysfunctional adipose tissue, was greater in Om and correlated with higher level of tissue TGFß signaling activity and lower ASC differentiation. We conclude that glucocorticoids restrain cell-autonomous TGFß signaling in ASCs to facilitate adipogenesis and healthy remodeling in Abdsc and these processes are impaired in Om. Therapies directed at overcoming glucocorticoid resistance in visceral adipose tissue may improve remodeling and help prevent metabolic complications of visceral obesity.
Assuntos
Tecido Adiposo/metabolismo , Fibrose/metabolismo , Glucocorticoides/farmacologia , Omento/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Ativinas/genética , Ativinas/metabolismo , Adipogenia/efeitos dos fármacos , Adipogenia/genética , Tecido Adiposo/citologia , Adulto , Dexametasona/farmacologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Fibrose/genética , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , Omento/efeitos dos fármacos , Proteoglicanas/genética , Proteoglicanas/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/genética , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , Fator de Crescimento Transformador beta/genética , Adulto JovemRESUMO
BACKGROUND: Attention deficits have been linked to poor recovery after stroke and may predict outcome. We explored the influence of attention on functional recovery post stroke in the first 12 months after discharge from hospital. METHODS: People with stroke completed measures of attention, balance, mobility and activities of daily living (ADL) ability at the point of discharge from hospital, and 6 and 12 months later. We used correlational analysis and stepwise linear regression to explore potential predictors of outcome. RESULTS: We recruited 122 men and women, mean age 70 years. At discharge, 56 (51%) had deficits of divided attention, 45 (37%) of sustained attention, 43 (36%) of auditory selective attention and 41 (37%) had visual selective attention deficits. Attention at discharge correlated with mobility, balance and ADL outcomes 12 months later. After controlling for the level of the outcome at discharge, correlations remained significant in only five of the 12 relationships. Stepwise linear regression revealed that the outcome measured at discharge, days until discharge and number of medications were better predictors of outcome: in no case was an attention variable at discharge selected as a predictor of outcome at 12 months. CONCLUSIONS: Although attention and function correlated significantly, this correlation was reduced after controlling for functional ability at discharge. Furthermore, side of lesion and the attention variables were not demonstrated as important predictors of outcome 12 months later.
Assuntos
Atividades Cotidianas/classificação , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Exame Neurológico , Testes Neuropsicológicos , Alta do Paciente , Acidente Vascular Cerebral/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/reabilitação , Comorbidade , Dominância Cerebral/fisiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estatística como Assunto , Acidente Vascular Cerebral/epidemiologia , Reabilitação do Acidente Vascular CerebralRESUMO
BACKGROUND: falls are common following a stroke, but knowledge about predicting future fallers is lacking. OBJECTIVE: to identify, at discharge from hospital, those who are most at risk of repeated falls. METHODS: consecutively hospitalised people with stroke (independently mobile prior to stroke and with intact gross cognitive function) were recruited. Subjects completed a battery of tests (balance, function, mood and attention) within 2 weeks of leaving hospital and at 12 months post hospital discharge. RESULTS: 122 participants (mean age 70.2 years) were recruited. Fall status at 12 months was available for 115 participants and of those, 63 [55%; 95% confidence interval (CI) 46-64] experienced one or more falls, 48 (42%; 95% CI 33-51) experienced repeated falls, and 62 (54%) experienced near-falls. All variables available at discharge were screened as potential predictors of falling. Six variables emerged [near-falling in hospital, Rivermead leg and trunk score, Rivermead upper limb score, Berg Balance score, mean functional reach, and the Nottingham extended activities of daily living (NEADL) score]. A score of near-falls in hospital and upper limb function was the best predictor with 70% specificity and 60% sensitivity. CONCLUSION: participants who were unstable (near-falls) in hospital with poor upper limb function (unable to save themselves) were most at risk of falls.