ABSTRACT
Three studies that used experimental manipulations of stimulus context and correlational analyses were conducted to examine how contextual effects influence magnitude estimation and the crossover effect on line bisection. Previous work had shown that although orienting attention to one end of a line prior to bisection determines the direction in which crossover occurs, bias in magnitude estimation actually produces the crossover effect. The influence of contextual effects on magnitude estimation, however, was not examined in these previous models of crossover. Consequently, the purpose of the present investigation was to examine these effects. Subjects in the current studies were healthy controls and people who had right and left hemisphere injury due to stroke, both with and without spatial neglect. Study 1 examined the crossover effect for lines bisected with and without a stimulus context. Study 2 examined both stimulus order as well as response order context effects on magnitude estimation. Study 3 examined how much variance in magnitude estimation was accounted for by stimulus contextual effects and how stimulus context influenced the crossover effect. The results showed that contextual bias was ubiquitous but relatively small in the magnitude estimates of normal subjects. Contextual bias was exaggerated to a similar degree in subjects with right or left hemisphere injury due to stroke, but the amount of variance accounted by contextual bias was still quite small. A novel finding of study 2 was that contextual effects can be induced by previous responses to stimuli as well as by the magnitude of preceding stimuli in subjects with unilateral brain injury. This may be a contextual effect related to response perseveration. Finally, studies 1 and 3 indicated that contextual effects strengthened the crossover effect on line bisection, primarily on relatively short lines. Contextual effects, however, cannot fully account for the crossover effect, because crossover bisections were observed also in the absence of a stimulus context. It is concluded that the crossover effect is explained by biases in attentional orientation and magnitude estimation. Contextual effects represent one source of bias in magnitude estimation that influences the crossover effect by promoting contralateral errors on short line lengths (<2 cm).
ABSTRACT
BACKGROUND: High-fat meal (HFM) consumption may induce transient postprandial atherogenic responses, including impairment of vascular endothelial function, in individuals with overweight/obesity. Red beetroot juice (RBJ) may modulate endothelial function and other measures of cardiometabolic health. OBJECTIVE: This study investigated the impact of acute and chronic RBJ consumption, including nitrate-dependent and -independent effects, on postprandial endothelial function and other cardiometabolic responses to a HFM. METHODS: Fifteen men and postmenopausal women with overweight/obesity were enrolled in this randomized, double-blind, placebo-controlled, 4-period, crossover clinical trial. Following an overnight fast, participants underwent baseline assessment of endothelial function (reactive hyperemia index; RHI) and hemodynamics, and biological sample collection. In random order, participants consumed 70 mL (acute visit) of: 1) RBJ, 2) nitrate-free RBJ (NF-RBJ), 3) placebo + nitrate (PBO + NIT), or 4) placebo (PBO), followed by a HFM. RHI was remeasured 4 h post-HFM, and hemodynamic assessment and biological sample collection were performed 1, 2, and 4 h post-HFM consumption. Participants consumed treatments daily for 4 wk (chronic visit), and assessments were repeated before/after the HFM (without consuming treatments). RESULTS: HFM consumption did not induce significant impairment of postprandial RHI. No significant differences in RHI were detected across treatment groups following acute or chronic exposure, despite increases in circulating nitrate/nitrite (NOx) concentrations in the RBJ and PBO + NIT groups compared with PBO and NF-RBJ (P < 0.0001 for all time points at the acute visit; P < 0.05 for all time points at the chronic visit). Although the HFM led to significant alterations in several secondary outcomes, there were no consistent treatment effects on postprandial cardiometabolic responses. CONCLUSIONS: HFM consumption did not impair postprandial endothelial function in this population, and RBJ exposure did not alter postprandial endothelial function or other outcomes despite increasing NOx concentrations. This trial is registered at clinicaltrials.gov as NCT02949115.
ABSTRACT
Previous research suggests potential for fresh pears as a functional food for promoting cardiometabolic health. The purpose of this randomized, open-label, placebo-controlled, crossover clinical trial was to evaluate the influence of daily fresh pear consumption on blood pressure (primary outcome) and other biomarkers of cardiometabolic health in middle-aged/older adults with metabolic syndrome (MetS). Forty men and women aged 45-65 years with MetS were included and randomly assigned to receive either two medium-sized fresh pears (Pear) or a calorie-matched control drink (Control) per day for each 12-week treatment period, each separated by a 4-week washout period. After 12 weeks of daily fresh pear consumption, systolic blood pressure tended to be reduced (130 ± 2 mmHg vs. 134 ± 2 mmHg at baseline, P = 0.07) and pulse pressure was significantly reduced (51 ± 1 vs. 54 ± 1 at baseline, P < 0.05). At 12 weeks, leptin concentrations were lower in the Pear group than Control (52.5 [7.6, 120.5] ng dL-1vs. 53.4 [5.0, 120.5] ng dL-1, respectively, P < 0.05), and there was a significant group by time interaction (P < 0.05). Leptin concentrations were significantly reduced at 12 weeks compared to baseline in the Pear group (52.5 [7.6, 120.5] ng dL-1vs. 54.8 [6.4, 120.5] ng dL-1 at baseline, P < 0.05) but not in the Control group. Waist circumference was significantly reduced at 12 weeks in the Pear group (107.7 ± 2.0 cm vs. 108.4 ± 2 cm at baseline, P < 0.05) with a trend for a group by time interaction (P < 0.1), and significantly lower in the Pear group than Control (108.1 ± 2.0 cm vs. 108.8 ± 2 cm, P < 0.05) at 6 weeks with a significant group by time interaction (P < 0.05). Conversely, values were significantly increased at 6 weeks (108.8 ± 2 cm vs. 108.3 ± 2.0 cm at baseline, P < 0.05) in the Control group and sustained at 12 weeks. Waist-to-hip ratio was significantly reduced (0.92 ± 0.01 vs. 0.93 ± 0.01 at baseline, P < 0.05) at 12 weeks in the Pear group, and significantly lower than Control at 6 weeks (0.93 ± 0.01 vs. 0.93 ± 0.01, respectively, P < 0.05) and 12 weeks (0.92 ± 0.01 vs. 0.93 ± 0.01, P < 0.05). These findings suggest that daily fresh pear consumption may promote modest improvements in cardiometabolic health in middle-aged/older adults with MetS. This trial was registered at clinicaltrials.gov as NCT02228837.
Subject(s)
Diet , Fruit , Metabolic Syndrome/diet therapy , Pyrus , Aged , Biomarkers , Body Composition , Energy Metabolism , Exercise , Female , Humans , Male , Middle AgedABSTRACT
The mechanistic target of rapamycin complex 1 (mTORC1) increases translation, cell size and angiogenesis, and inhibits autophagy. mTORC1 is negatively regulated by hamartin and tuberin, the protein products of the tumor suppressors TSC1 and TSC2 that are mutated in Tuberous Sclerosis Complex (TSC) and sporadic Lymphangioleiomyomatosis (LAM). Hamartin interacts with the centrosomal and mitotic kinase polo-like kinase 1 (PLK1). Hamartin and tuberin deficient cells have abnormalities in centrosome duplication, mitotic progression, and cytokinesis, suggesting that the hamartin/tuberin heterodimer and mTORC1 signaling are involved in centrosome biology and mitosis. Here we report that PLK1 protein levels are increased in hamartin and tuberin deficient cells and LAM patient-derived specimens, and that this increase is rapamycin-sensitive. Pharmacological inhibition of PLK1 by the small-molecule inhibitor BI-2536 significantly decreased the viability and clonogenic survival of hamartin and tuberin deficient cells, which was associated with increased apoptosis. BI-2536 increased p62, LC3B-I and GFP-LC3 punctae, and inhibited HBSS-induced degradation of p62, suggesting that PLK1 inhibition attenuates autophagy. Finally, PLK1 inhibition repressed the expression and protein levels of key autophagy genes and proteins and the protein levels of Bcl(-)2 family members, suggesting that PLK1 regulates both autophagic and apoptotic responses. Taken together, our data point toward a previously unrecognized role of PLK1 on the survival of cells with mTORC1 hyperactivation, and the potential use of PLK1 inhibitors as novel therapeutics for tumors with dysregulated mTORC1 signaling, including TSC and LAM.
