Impairment of Rat Fetal Beta-Cell Development by Maternal Exposure to Dexamethasone during Different Time-Windows

Glucocorticoids (GCs) take part in the direct control of cell lineage during the late phase of pancreas development when endocrine and exocrine cell differentiation occurs. However, other tissues such as the vasculature exert a critical role before that phase. This study aims to investigate the consequences of overexposure to exogenous glucocorticoids during different time-windows of gestation for the development of the fetal endocrine pancreas

What autocorrelation tells us about motor variability: Insights from dart throwing

In sports such as golf and darts it is important that one can produce ballistic movements of an object towards a goal location with as little variability as possible. A factor that influences this variability is the extent to which motor planning is updated from movement to movement based on observed errors. Previous work has shown that for reaching movements, our motor system uses the learning rate (the proportion of an error that is corrected for in the planning of the next movement) that is optimal for minimizing the endpoint variability. Here we examined whether the learning rate is hard-wired and therefore automatically optimal, or whether it is optimized through experience. We compared the performance of experienced dart players and beginners in a dart task. A hallmark of the optimal learning rate is that the lag-1 autocorrelation of movement endpoints is zero. We found that the lag-1 autocorrelation of experienced dart players was near zero, implying a near-optimal learning rate, whereas it was negative for beginners, suggesting a larger than optimal learning rate. We conclude that learning rates for trial-by-trial motor learning are optimized through experience. This study also highlights the usefulness of the lag-1 autocorrelation as an index of performance in studying motor-skill learning

Prenatal Excess Glucocorticoid Exposure and Adult Affective Disorders:A Role for Serotonergic and Catecholamine Pathways

Fetal glucocorticoid exposure is a key mechanism proposed to underlie prenatal ‘programming’ of adult affective behaviours such as depression and anxiety. Indeed, the glucocorticoid metabolising enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which is highly expressed in the placenta and the developing fetus, acts as a protective barrier from the high maternal glucocorticoids which may alter developmental trajectories. The programmed changes resulting from maternal stress or bypass or from the inhibition of 11β-HSD2 are frequently associated with alterations in the hypothalamic-pituitary-adrenal (HPA) axis. Hence, circulating glucocorticoid levels are increased either basally or in response to stress accompanied by CNS region-specific modulations in the expression of both corticosteroid receptors (mineralocorticoid and glucocorticoid receptors). Furthermore, early-life glucocorticoid exposure also affects serotonergic and catecholamine pathways within the brain, with changes in both associated neurotransmitters and receptors. Indeed, global removal of 11β-HSD2, an enzyme that inactivates glucocorticoids, increases anxiety‐ and depressive-like behaviour in mice; however, in this case the phenotype is not accompanied by overt perturbation in the HPA axis but, intriguingly, alterations in serotonergic and catecholamine pathways are maintained in this programming model. This review addresses one of the potential adverse effects of glucocorticoid overexposure in utero, i.e. increased incidence of affective behaviours, and the mechanisms underlying these behaviours including alteration of the HPA axis and serotonergic and catecholamine pathways

Placental phenotypes of intrauterine growth

The placenta is essential to nutrition before birth. Recent work has shown that a range of clearly defined alterations can be found in the placentas of infants with intrauterine growth restriction (IUGR). In the mouse, a placental specific knockout of a single imprinted gene, encoding IGF-2, results in one pattern of alterations in placenta structure and function which leads to IUGR. We speculate that the alterations in the human placenta can also be grouped into patterns, or phenotypes, that are associated with specific patterns of fetal growth. Identifying the placental phenotypes of different fetal growth patterns will improve the ability of clinicians to recognize high-risk patients, of laboratory scientists to disentangle the complexities of IUGR, and of public health teams to target interventions aimed at ameliorating the long-term adverse effects of inadequate intrauterine growth

Prenatal exposure to Dexamethasone in the mouse alters cardiac growth patterns and increases pulse pressure in aged male offspring

Exposure to synthetic glucocorticoids during development can result in later cardiovascular and renal disease in sheep and rats. Although prenatal glucocorticoid exposure is associated with impaired renal development, less is known about effects on the developing heart. This study aimed to examine the effects of a short-term exposure to dexamethasone (60 hours from embryonic day 12.5) on the developing mouse heart, and cardiovascular function in adult male offspring. Dexamethasone (DEX) exposed fetuses were growth restricted compared to saline treated controls (SAL) at E14.5, but there was no difference between groups at E17.5. Heart weights of the DEX fetuses also tended to be smaller at E14.5, but not different at E17.5. Cardiac AT(1a)R, Bax, and IGF-1 mRNA expression was significantly increased by DEX compared to SAL at E17.5. In 12-month-old offspring DEX exposure caused an increase in basal blood pressure of similar to 3 mmHg. In addition, DEX exposed mice had a widened pulse pressure compared to SAL. DEX exposed males at 12 months had an approximate 25% reduction in nephron number compared to SAL, but no difference in cardiomyocyte number. Exposure to DEX in utero appears to adversely impact on nephrogenesis and heart growth but is not associated with a cardiomyocyte deficit in male mice in adulthood, possibly due to compensatory growth of the myocardium following the initial insult. However, the widened pulse pressure may be indicative of altered vascular compliance

Tests examining skill outcomes in sport: A systematic review of measurement properties and feasibility

BackgroundA high level of participant skill is influential in determining the outcome of many sports. Thus, tests assessing skill outcomes in sport are commonly used by coaches and researchers to estimate an athlete&rsquo;s ability level, to evaluate the effectiveness of interventions or for the purpose of talent identification.ObjectiveThe objective of this systematic review was to examine the methodological quality, measurement properties and feasibility characteristics of sporting skill outcome tests reported in the peer-reviewed literature.Data SourcesA search of both SPORTDiscus and MEDLINE databases was undertaken.Study SelectionStudies that examined tests of sporting skill outcomes were reviewed. Only studies that investigated measurement properties of the test (reliability or validity) were included. A total of 22 studies met the inclusion/exclusion criteria.Study Appraisal and Synthesis MethodsA customised checklist of assessment criteria, based on previous research, was utilised for the purpose of this review.ResultsA range of sports were the subject of the 22 studies included in this review, with considerations relating to methodological quality being generally well addressed by authors. A range of methods and statistical procedures were used by researchers to determine the measurement properties of their skill outcome tests. The majority (95 %) of the reviewed studies investigated test&ndash;retest reliability, and where relevant, inter and intra-rater reliability was also determined. Content validity was examined in 68 % of the studies, with most tests investigating multiple skill domains relevant to the sport. Only 18 % of studies assessed all three reviewed forms of validity (content, construct and criterion), with just 14 % investigating the predictive validity of the test. Test responsiveness was reported in only 9 % of studies, whilst feasibility received varying levels of attention.LimitationsIn organised sport, further tests may exist which have not been investigated in this review. This could be due to such tests firstly not being published in the peer-review literature and secondly, not having their measurement properties (i.e., reliability or validity) examined formally.ConclusionsOf the 22 studies included in this review, items relating to test methodological quality were, on the whole, well addressed. Test&ndash;retest reliability was determined in all but one of the reviewed studies, whilst most studies investigated at least two aspects of validity (i.e., content, construct or criterion-related validity). Few studies examined predictive validity or responsiveness. While feasibility was addressed in over half of the studies, practicality and test limitations were rarely addressed. Consideration of study quality, measurement properties and feasibility components assessed in this review can assist future researchers when developing or modifying tests of sporting skill outcomes.<br /