Effects of grapefruit, grapefruit juice and water preloads on energy balance, weight loss, body composition, and cardiometabolic risk in free-living obese adults

<p>Abstract</p> <p>Background</p> <p>Reducing dietary energy density has proven to be an effective strategy to reduce energy intakes and promote weight control. This effect appears most robust when a low energy dense preload is consumed before meals. Yet, much discussion continues regarding the optimal form of a preload. The purpose of the present study was to compare effects of a solid (grapefruit), liquid (grapefruit juice) and water preload consumed prior to breakfast, lunch and dinner in the context of caloric restriction.</p> <p>Methods</p> <p>Eighty-five obese adults (BMI 30-39.9) were randomly assigned to (127 g) grapefruit (GF), grapefruit juice (GFJ) or water preload for 12 weeks after completing a 2-week caloric restriction phase. Preloads were matched for weight, calories, water content, and energy density. Weekly measures included blood pressure, weight, anthropometry and 24-hour dietary intakes. Resting energy expenditure, body composition, physical performance and cardiometabolic risk biomarkers were assessed.</p> <p>Results</p> <p>The total amount (grams) of food consumed did not change over time. Yet, after preloads were combined with caloric restriction, average dietary energy density and total energy intakes decreased by 20-29% from baseline values. Subjects experienced 7.1% weight loss overall, with significant decreases in percentage body, trunk, android and gynoid fat, as well as waist circumferences (-4.5 cm). However, differences were not statistically significant among groups. Nevertheless, the amount and direction of change in serum HDL-cholesterol levels in GF (+6.2%) and GFJ (+8.2%) preload groups was significantly greater than water preload group (-3.7%).</p> <p>Conclusions</p> <p>These data indicate that incorporating consumption of a low energy dense dietary preload in a caloric restricted diet is a highly effective weight loss strategy. But, the form of the preload did not have differential effects on energy balance, weight loss or body composition. It is notable that subjects in GF and GFJ preload groups experienced significantly greater benefits in lipid profiles.</p> <p>Trial registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00581074">NCT00581074</a></p

The SR-BI Partner PDZK1 Facilitates Hepatitis C Virus Entry

Entry of hepatitis C virus (HCV) into hepatocytes is a multi-step process that involves a number of different host cell factors. Following initial engagement with glycosaminoglycans and the low-density lipoprotein receptor, it is thought that HCV entry proceeds via interactions with the tetraspanin CD81, scavenger receptor class B type I (SR-BI), and the tight-junction proteins claudin-1 (CLDN1) and occludin (OCLN), culminating in clathrin-dependent endocytosis of HCV particles and their pH-dependent fusion with endosomal membranes. Physiologically, SR-BI is the major receptor for high-density lipoproteins (HDL) in the liver, where its expression is primarily controlled at the post-transcriptional level by its interaction with the scaffold protein PDZK1. However, the importance of interaction with PDZK1 to the involvement of SR-BI in HCV entry is unclear. Here we demonstrate that stable shRNA-knockdown of PDZK1 expression in human hepatoma cells significantly reduces their susceptibility to HCV infection, and that this effect can be reversed by overexpression of full length PDZK1 but not the first PDZ domain of PDZK1 alone. Furthermore, we found that overexpression of a green fluorescent protein chimera of the cytoplasmic carboxy-terminus of SR-BI (amino acids 479–509) in Huh-7 cells resulted in its interaction with PDZK1 and a reduced susceptibility to HCV infection. In contrast a similar chimera lacking the final amino acid of SR-BI (amino acids 479–508) failed to interact with PDZK1 and did not inhibit HCV infection. Taken together these results indicate an indirect involvement of PDZK1 in HCV entry via its ability to interact with SR-BI and enhance its activity as an HCV entry factor

Association of alpha-aminoadipic acid with cardiometabolic risk factors in healthy and high-risk individuals

IntroductionPlasma levels of the metabolite alpha-aminoadipic acid (2-AAA) have been associated with risk of type 2 diabetes (T2D) and atherosclerosis. However, little is known about the relationship of 2-AAA to other cardiometabolic risk markers in pre-disease states, or in the setting of comorbid disease.MethodsWe measured circulating 2-AAA using two methods in 1) a sample of 261 healthy individuals (2-AAA Study), and 2) in a sample of 134 persons comprising 110 individuals with treated HIV, with or without T2D, a population at high risk of metabolic disease and cardiovascular events despite suppression of circulating virus, and 24 individuals with T2D without HIV (HATIM Study). We examined associations between plasma 2-AAA and markers of cardiometabolic health within each cohort.Results and discussionWe observed differences in 2-AAA by sex and race in both cohorts, with higher levels observed in men compared with women, and in Asian compared with Black or white individuals (P&lt;0.05). There was no significant difference in 2-AAA by HIV status within individuals with T2D in the HATIM Study. We confirmed associations between 2-AAA and dyslipidemia in both cohorts, where high 2-AAA associated with low HDL cholesterol (P&lt;0.001) and high triglycerides (P&lt;0.05). As expected, within the cohort of people with HIV, 2-AAA was higher in the setting of T2D compared to pre-diabetes or normoglycemia (P&lt;0.001). 2-AAA was positively associated with body mass index (BMI) in the 2-AAA Study, and with waist circumference and measures of visceral fat volume in HATIM (all P&lt;0.05). Further, 2-AAA associated with increased liver fat in persons with HIV (P&lt;0.001). Our study confirms 2-AAA as a marker of cardiometabolic risk in both healthy individuals and those at high cardiometabolic risk, reveals relationships with adiposity and hepatic steatosis, and highlights important differences by sex and race. Further studies are warranted to establish molecular mechanisms linking 2-AAA to disease in other high-risk populations

Caregiving process and caregiver burden: Conceptual models to guide research and practice

BACKGROUND: Parental care for a child with a developmental disability is an enormous responsibility, one that can far exceed that of typical parental care. While most parents adapt well to the situation of caring for a child with a disability, some do not. To understand parents' adaptations to their children's disabilities, the complex nature of stress processes must be accounted for and the constructs and factors that play a role in the caregiving must be considered. DISCUSSION: Evidence suggests that there is considerable variation in how caregivers adapt to their caregiving demands. Many studies have sought to qualify the association between caregiving and health outcomes of the caregivers. Contextual factors such as SES, child factors such as child behaviour problems and severity of disability, intra-psychic factors such as mastery and self-esteem, coping strategies and social supports have all been associated with psychological and/or physical outcome or parents or primary caregivers. In reviewing these issues, the literature appears to be limited by the use of traditional analytic approaches which examine the relationship between a factor and an outcome. It is clear, however, that changes to single factors, as represented in these studies, occur very rarely even in the experimental context. The literature has also been limited by lack of reliance on specific theoretical frameworks. SUMMARY: This conceptual paper documents the state of current knowledge and explores the current theoretical frameworks that have been used to describe the caregiving process from two diverse fields, pediatrics and geriatrics. Integration of these models into one comprehensive model suitable for this population of children with disabilities and their caregivers is proposed. This model may guide future research in this area

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong