2,488 research outputs found

    Maternal obesity is associated with the formation of small dense LDL and hypoadiponectinemia in the third trimester

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    Context: Maternal obesity is associated with high plasma triglyceride, poor vascular function, and an increased risk for pregnancy complications. In normal-weight pregnant women, higher triglyceride is associated with increased small, dense low-density lipoprotein (LDL). Hypothesis: In obese pregnancy, increased plasma triglyceride concentrations result in triglyceride enrichment of very low-density lipoprotein-1 particles and formation of small dense LDL via lipoprotein lipase. Design: Women (n = 55) of body mass index of 18–46 kg/m2 were sampled longitudinally at 12, 26, and 35 weeks' gestation and 4 months postnatally. Setting: Women were recruited at hospital antenatal appointments, and study visits were in a clinical research suite. Outcome Measures: Plasma concentrations of lipids, triglyceride-rich lipoproteins, lipoprotein lipase mass, estradiol, steroid hormone binding globulin, insulin, glucose, leptin, and adiponectin were determined. Results: Obese women commenced pregnancy with higher plasma triglyceride, reached the same maximum, and then returned to higher postnatal levels than normal-weight women. Estradiol response to pregnancy (trimester 1–3 incremental area under the curve) was positively associated with plasma triglyceride response (r2 adjusted 25%, P < .001). In the third trimester, the proportion of small, dense LDL was 2-fold higher in obese women than normal-weight women [mean (SD) 40.7 (18.8) vs 21.9 (10.9)%, P = .014], and 35% of obese, 14% of overweight, and none of the normal-weight women displayed an atherogenic LDL subfraction phenotype. The small, dense LDL mass response to pregnancy was inversely associated with adiponectin response (17%, P = .013). Conclusions: Maternal obesity is associated with an atherogenic LDL subfraction phenotype and may provide a mechanistic link to poor vascular function and adverse pregnancy outcome

    Mentalising skills in generic mental healthcare settings: can we make our day-to-day interactions more therapeutic?

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    Aims and method: Caring for patients with personality disorder is one of the biggest challenges in psychiatric work. We investigated whether mentalisation-based treatment skills (MBT-S) teaching improves clinicians' understanding of mentalising and attitudes towards personality disorder. Self-report questionnaires (Knowledge and Application of MBT (KAMQ) and Attitudes to Personality Disorder (APDQ)) were completed at baseline and after a 2-day MBT-S workshop. Results: Ninety-two healthcare professionals completed questionnaires before and after training. The mean within-participant increase in scores from baseline to end-of-programme was 11.6 points (95% CI 10.0-13.3) for the KAMQ and 4.0 points (1.8-6.2) for the APDQ. Clinical implications: MBT-S is a short intervention that is effective in improving clinicians' knowledge of personality disorder and mentalisation. That attitudes to personality disorder improved overall is encouraging in relation to the possibility of deeper learning in staff and, ultimately, improved care for patients with personality disorder. Declaration of interest: None

    Activation of AMPK by bitter melon triterpenoids involves CaMKKβ

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    We recently showed that bitter melon-derived triterpenoids (BMTs) activate AMPK and increase GLUT4 translocation to the plasma membrane in vitro, and improve glucose disposal in insulin resistant models in vivo. Here we interrogated the mechanism by which these novel compounds activate AMPK, a leading anti-diabetic drug target. BMTs did not activate AMPK directly in an allosteric manner as AMP or the Abbott compound (A-769662) does, nor did they activate AMPK by inhibiting cellular respiration like many commonly used anti-diabetic medications. BMTs increased AMPK activity in both L6 myotubes and LKB1-deficient HeLa cells by 20-35%. Incubation with the CaMKKß inhibitor, STO-609, completely attenuated this effect suggesting a key role for CaMKKß in this activation. Incubation of L6 myotubes with the calcium chelator EGTA-AM did not alter this activation suggesting that the BMT-dependent activation was Ca2+-independent. We therefore propose that CaMKKß is a key upstream kinase for BMT-induced activation of AMPK

    Manipulation of flavour and aroma compound sequestration and release using a glycosyltransferase with specificity for terpene alcohols.

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    Glycosides are an important potential source of aroma and flavour compounds for release as volatiles in flowers and fruit. The production of glycosides is catalysed by UDP-glycosyltransferases (UGTs) that mediate the transfer of an activated nucleotide sugar to acceptor aglycones. A screen of UGTs expressed in kiwifruit (Actinidia deliciosa) identified the gene AdGT4 which was highly expressed in floral tissues and whose expression increased during fruit ripening. Recombinant AdGT4 enzyme glycosylated a range of terpenes and primary alcohols found as glycosides in ripe kiwifruit. Two of the enzyme's preferred alcohol aglycones, hexanol and (Z)-hex-3-enol, contribute strongly to the 'grassy-green' aroma notes of ripe kiwifruit and other fruit including tomato and olive. Transient over-expression of AdGT4 in tobacco leaves showed that enzyme was able to glycosylate geraniol and octan-3-ol in planta whilst transient expression of an RNAi construct in Actinidia eriantha fruit reduced accumulation of a range of terpene glycosides. Stable over-expression of AdGT4 in transgenic petunia resulted in increased sequestration of hexanol and other alcohols in the flowers. Transgenic tomato fruit stably over-expressing AdGT4 showed changes in both the sequestration and release of a range of alcohols including 3-methylbutanol, hexanol and geraniol. Sequestration occurred at all stages of fruit ripening. Ripe fruit sequestering high levels of glycosides were identified as having a less intense, earthier aroma in a sensory trial. These results demonstrate the importance of UGTs in sequestering key volatile compounds in planta and suggest a future approach to enhancing aromas and flavours in flowers and during fruit ripening. Yauk YK1, Ged C, Wang MY, Matich AJ, Tessarotto L, Cooney JM, Chervin C, Atkinson RG

    The Changing Face of Neolithic and Bronze Age Ireland: A Big Data Approach to the Settlement and Burial Records

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    This paper synthesizes and analyses the spatial and temporal patterns of archaeological sites in Ireland spanning the Neolithic period and the Bronze Age transition (4300-1900 cal BC). Included are a large number of unpublished, newly discovered sites excavated through development-led projects. Data were also sourced from national archives, published excavation reports and on-line databases. Software tools were developed to deal with the varying nature and resolution of these datasets, allowing chronology to be considered in the analysis to a degree that is usually not possible in prehistoric studies. Summed radiocarbon probabilities are used to examine the dataset using context- and sample-sensitive approaches. Visualisations of spatial and chronological data illustrate the expansion of Early Neolithic settlement, followed by an apparent attenuation of all settlement activity. The Late Neolithic and Chalcolithic periods are characterised by a resurgence and diversification of activity. To assess the significance of these observations, Irish radiocarbon data are compared to an idealized model derived from North American data. Even after taking various considerations into account, human population increases can be suggested to have occurred during the Early and Late Neolithic periods. Gaps and biases in the data are discussed and priorities for future work are identified

    Achievement of treatment goals for primary prevention of cardiovascular disease in clinical practice across Europe: the EURIKA study

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    Aims: Most studies on the primary prevention of cardiovascular disease (CVD) have been limited to patients at high CVD risk. We assessed the achievement of treatment goals for CVD risk factors among patients with a substantial variation in CVD risk. Methods and results: This study was conducted with 7641 outpatients aged ≥50 years, free of clinical CVD and with at least one major CVD risk factor, selected from 12 European countries in 2009. Risk factor definition and treatment goals were based on the 2007 European guidelines on CVD prevention. Cholesterol fractions and glycated haemoglobin (HbA1c) were measured in a central laboratory. Cardiovascular disease risk was estimated with the SCORE equation. Patients' mean age was 63 years (48% men), and 40.1% had a high CVD risk. Among treated hypertensives (94.2%), only 38.8% achieved the blood pressure target of <140/90 mmHg [between-country range (BCR): 32.1–47.5%]. Among treated dyslipidaemic patients (74.4%), 41.2% attained both the total- and LDL-cholesterol target of <5 and <3 mmol/L, respectively (BCR: 24.3–68.4%). Among treated type 2 diabetic patients (87.2%), 36.7% achieved the <6.5% HbA1c target (BCR: 23.4–48.4%). Among obese patients on non-pharmacological treatment (92.2%), 24.7% reached the body mass index target of <30 kg/m2 (BCR: 12.7–37.1%). About one-third of controlled patients on treatment were still at high remaining CVD risk. Although most patients were advised to reduce excess weight and to follow a low-calorie diet, less than half received written recommendations. Conclusions: In Europe, a large proportion of patients in primary prevention have CVD risk factors that remain uncontrolled, and lifestyle counselling is not well implemented; moreover, there is substantial between-country variation, which indicates additional room for improvement. Raised residual CVD risk is relatively frequent among patients despite control of their primary risk factors and should be addressed

    Analysis of the rotation period of asteroids (1865) Cerberus, (2100) Ra-Shalom, and (3103) Eger - search for the YORP effect

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    The spin state of small asteroids can change on a long timescale by the Yarkovsky-O'Keefe-Radzievskii-Paddack (YORP) effect, the net torque that arises from anisotropically scattered sunlight and proper thermal radiation from an irregularly-shaped asteroid. The secular change in the rotation period caused by the YORP effect can be detected by analysis of asteroid photometric lightcurves. We analyzed photometric lightcurves of near-Earth asteroids (1865) Cerberus, (2100) Ra-Shalom, and (3103) Eger with the aim to detect possible deviations from the constant rotation caused by the YORP effect. We carried out new photometric observations of the three asteroids, combined the new lightcurves with archived data, and used the lightcurve inversion method to model the asteroid shape, pole direction, and rotation rate. The YORP effect was modeled as a linear change in the rotation rate in time d\omega /dt. Values of d\omega/ dt derived from observations were compared with the values predicted by theory. We derived physical models for all three asteroids. We had to model Eger as a nonconvex body because the convex model failed to fit the lightcurves observed at high phase angles. We probably detected the acceleration of the rotation rate of Eger d\omega / dt = (1.4 +/- 0.6) x 10^{-8} rad/d (3\sigma error), which corresponds to a decrease in the rotation period by 4.2 ms/yr. The photometry of Cerberus and Ra-Shalom was consistent with a constant-period model, and no secular change in the spin rate was detected. We could only constrain maximum values of |d\omega / dt| < 8 x 10^{-9} rad/d for Cerberus, and |d\omega / dt| < 3 x 10^{-8} rad/d for Ra-Shalom
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