Lifestyle intervention in obese pregnancy and cardiac remodelling in 3-year olds: children of the UPBEAT RCT.

BACKGROUND/OBJECTIVES: Obesity in pregnancy has been associated with increased childhood cardiometabolic risk and reduced life expectancy. The UK UPBEAT multicentre randomised control trial was a lifestyle intervention of diet and physical activity in pregnant women with obesity. We hypothesised that the 3-year-old children of women with obesity would have heightened cardiovascular risk compared to children of normal BMI women, and that the UPBEAT intervention would mitigate this risk. SUBJECTS/METHODS: Children were recruited from one UPBEAT trial centre. Cardiovascular measures included blood pressure, echocardiographic assessment of cardiac function and dimensions, carotid intima-media thickness and heart rate variability (HRV) by electrocardiogram. RESULTS: Compared to offspring of normal BMI women (n = 51), children of women with obesity from the trial standard care arm (n = 39) had evidence of cardiac remodelling including increased interventricular septum (IVS; mean difference 0.04 cm; 95% CI: 0.018 to 0.067), posterior wall (PW; 0.03 cm; 0.006 to 0.062) and relative wall thicknesses (RWT; 0.03 cm; 0.01 to 0.05) following adjustment. Randomisation of women with obesity to the intervention arm (n = 31) prevented this cardiac remodelling (intervention effect; mean difference IVS -0.03 cm (-0.05 to -0.008); PW -0.03 cm (-0.05 to -0.01); RWT -0.02 cm (-0.04 to -0.005)). Children of women with obesity (standard care arm) compared to women of normal BMI also had elevated minimum heart rate (7 bpm; 1.41 to 13.34) evidence of early diastolic dysfunction (e prime) and increased sympathetic nerve activity index by HRV analysis. CONCLUSIONS: Maternal obesity was associated with left ventricular concentric remodelling in 3-year-old offspring. Absence of remodelling following the maternal intervention infers in utero origins of cardiac remodelling. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: The UPBEAT trial is registered with Current Controlled Trials, ISRCTN89971375.

Circulating microRNAs as Diagnostic Markers in Primary Aldosteronism.

Primary aldosteronism (PA) is a common and highly treatable condition, usually resulting from adrenocortical tumorous growth or hyperplasia. PA is currently underdiagnosed owing to its complex and protracted diagnostic procedures. A simplified biomarker-based test would be highly valuable in reducing cardiovascular morbidity and mortality. Circulating microRNAs are emerging as potential biomarkers for a number of conditions due to their stability and accessibility. PA is known to alter microRNA expression in adrenocortical tissue; if these changes or their effects are mirrored in the circulating miRNA profile, then this could be exploited by a diagnostic test. However, the reproducibility of studies to identify biomarker-circulating microRNAs has proved difficult for other conditions due to a series of technical challenges. Therefore, any studies seeking to definitively identify circulating microRNA biomarkers of PA must address this in their design. To this end, we are currently conducting the circulating microRNA arm of the ongoing ENS@T-HT study. In this review article, we present evidence to support the utility of circulating microRNAs as PA biomarkers, describe the practical challenges to this approach and, using ENS@T-HT as an example, discuss how these might be overcome.

Emotional Availability, Neuropsychological Functioning, and Psychopathology: The Context of Parental Substance Use Disorder.

Parental Substance Use Disorder (SUD) constitutes a high-risk condition for parent-child interactions and child development. Empirical evidence indicates high rates of psychopathology and neuropsychological impairments in individuals with SUD. Despite research indicating that parenting skills are related to psychological well-being and cognitive/neuropsychological functioning, prior studies have not examined the associations between these areas of parental functioning and the quality of parent-child interactions in the context of SUD. Aim(s). The present study adopts an integrated perspective to investigate the way in which maternal neuropsychological functioning and psychopathology are associated with mother-child emotional availability (EA), in the context of parental Substance Use Disorder. Methods. Twenty-nine mothers with SUD were assessed in interaction with their children, as well as with respect to their neuropsychological functioning and psychopathology. Results. In this group, high rates of maternal neuropsychological impairments and psychopathology, as well as generally low levels of EA, were uncovered. Regression analyses showed that maternal neuropsychological functioning was significantly associated with mother-child EA, specifically sensitivity; the role of maternal psychopathology, however, was only marginally significant. Conclusion. In the context of SUD, maternal neuropsychological impairments are significantly associated with mother-child EA. Clinical implications of the findings are discussed.

A Neural Basis for Contagious Yawning.

Contagious yawning, in which yawning is triggered involuntarily when we observe another person yawn, is a common form of echophenomena-the automatic imitation of another's words (echolalia) or actions (echopraxia) [1]. The neural basis for echophenomena is unknown; however, it has been proposed that it is linked to disinhibition of the human mirror-neuron system [1-4] and hyper-excitability of cortical motor areas [1]. We investigated the neural basis for contagious yawning using transcranial magnetic stimulation (TMS). Thirty-six adults viewed video clips that showed another individual yawning and, in separate blocks, were instructed to either resist yawning or allow themselves to yawn. Participants were videoed throughout and their yawns or stifled yawns were counted. We used TMS to quantify motor cortical excitability and physiological inhibition for each participant, and these measures were then used to predict the propensity for contagious yawning across participants. We demonstrate that instructions to resist yawning increase the urge to yawn and alter how yawns are expressed (i.e., full versus stifled yawns) but do not alter the individual propensity for contagious yawning. By contrast, TMS measures of cortical excitability and physiological inhibition were significant predictors of contagious yawning and accounted for approximately 50% of the variability in contagious yawning. These data demonstrate that individual variability in the propensity for contagious yawning is determined by cortical excitability and physiological inhibition in the primary motor cortex.

Emotional availability: theory, research, and intervention.

Attachment theory (Bowlby, 1969) and its limitations are first described. Next, emotional availability (EA; Biringen et al., 1998; Biringen, 2008) is introduced as an expansion upon the original conceptualization of the parent-child attachment relationship. As a construct and as a measure, EA considers the dyadic and emotional qualities of adult-child relationships. EA is predictive of a variety of child outcomes, such as attachment security, emotion regulation, and school readiness. Recently developed programs to enhance adult-child EA are described.

Variations in phytoestrogen content between different mill dates of the same diet produces significant differences in the time of vaginal opening in CD-1 mice and F344 rats but not in CD Sprague-Dawley rats.

BACKGROUND: The optimum test diet and rodent species/strain for evaluating endocrine-disrupting compounds (EDCs) are critical. OBJECTIVES: We conducted studies to evaluate rodent species sensitivity and the effects of diets varying in phytoestrogen content on the time of vaginal opening (VO) in CD-1 mice, Fischer 344 (F344) rats, and CD Sprague-Dawley (S-D) rats. METHODS: Mice were weaned on postnatal day (PND) 15 and rats on PND19 and randomly assigned to control or test diets. Body weights, food consumption, and time of VO were recorded. RESULTS: The time of VO was significantly advanced in F344 rats fed diets containing daidzein and genistein, whereas these same diets did not advance VO in S-D rats. When animals were fed the AIN-76A diet spiked with genistein, time of VO was significantly advanced at all doses in CD-1 mice, at the two highest doses in F344 rats, and at the highest dose in S-D rats. The time of VO in F344 rats was more highly correlated with the phytoestrogen content than with the total metabolizable energy (ME) of 12 diets. CONCLUSIONS: The S-D rat is less sensitive to dietary phytoestrogens compared with the F344 rat or the CD-1 mouse, suggesting that the S-D rat is not the ideal model for evaluating estrogenic activity of EDCs. The profound effects of dietary phytoestrogens on the time of VO, an estrogen-sensitive marker, indicate that a standardized open-formula phytoestrogen-free diet containing a low ME level should be used to optimize the sensitivity of estrogenic bioassays.

Dietary phytoestrogens accelerate the time of vaginal opening in immature CD-1 mice.

The purpose of the study reported here was to determine the effects of dietary phytoestrogens on the time of vaginal opening (VO) in immature CD-1 mice, and to correlate it with phytoestrogen and total metabolizable energy (ME) contents of the diet in an effort to determine the most appropriate diets(s) for comparing or evaluating the estrogenic or antiestrogenic activity of endocrine disruptor compounds (EDC). Mice were weaned at postnatal day (PND) 15 and fed the test diets from PND 15 to 30. Vaginal opening was recorded from PND 20 to 30. The phytoestrogen content of the diet was highly predictive (P < 0.0001) of the proportion of mice with VO at PND 24. Total ME content also was significantly (P < 0.01) correlated with time of VO, although this variable was somewhat less predictive than was phytoestrogen content. Time of VO in mice was significantly (P < 0.05) accelerated in mice fed diets high in phytoestrogens, compared with those containing low phytoestrogen content. It was concluded that: dietary daidzein and genistein can significantly (P < 0.01) accelerate the time of VO in CD-1 mice; the advancement in time of VO is more highly correlated with daidzein and genistein contents of the diets than with total ME content; advancement in the time of VO is a sensitive end point for evaluating the estrogenic activity of EDCs, and should be part of the standard protocol for evaluating EDCs. Phytoestrogen-free diet(s) containing the same amount of ME should be used in bioassays that compare the time of VO, or increases in uterine weight as end points for evaluating the estrogenic activity of an EDC.

Dietary factors affecting uterine weights of immature CD-1 mice used in uterotrophic bioassays.

A study was conducted to determine the effects of dietary factors in natural ingredient and purified diets on uterine weights of immature CD-1 mice used in uterotrophic bioassays. Factors evaluated included body weight gain, dietary phytoestrogen content, total metabolizable energy, and percent crude fiber. Fifteen to 147 mice per group, housed 5 per cage, were randomly assigned to each of the 20 test diets. The test diets were fed for 7 days to 15-day old immature female CD-1 mice and their body weight gain and uterine weights were determined. Analysis of covariance procedures were used to evaluate differences in uterine weights, after adjusting for body weight and time-related trends. Fisher's least significant difference test was used to compare adjusted uterine weights and weight gains among the test diets. Additionally, multiple linear regression procedures were used to identify those characteristics of the rodent diet that were most predictive of the adjusted uterine weights. Total metabolizable energy was significantly (P < 0.01) correlated with and was predictive of uterine weights. The following dietary variables were not significantly predictive of uterine weights: total daidzein and genistein content, percent protein, fat, N-FE (carbohydrates) or percent crude fiber. We concluded that: (1) total metabolizable energy (ME) in natural ingredient or purified diets has a significant (P < 0.01) effect on the uterine weights of immature mice used in 7-day uterotrophic bioassays; (2) a standardized, estrogen-free diet with a constant level of ME should be used for conducting uterotrophic assays when comparing results between different laboratories or when determining the estrogenic or anti-estrogenic activity of endocrine disruptor compounds; (3) the mouse uterotrophic assay remains a sensitive bioassay for assessing chemicals for estrogenic activity or for the detection of total estrogenic activity in rodent diets that may be contaminated with estrogenic compounds, and (4) chemical assays should be used to detect or measure low levels of the phytoestrogens in rodent diets.