014 * SHOULD MILD-TO-MODERATE ISCHAEMIC MITRAL REGURGITATION BE CORRECTED IN PATIENTS WITH IMPAIRED LEFT VENTRICULAR FUNCTION UNDERGOING SIMULTANEOUS CORONARY REVASCULARIZATION?

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Accessory mitral valve tissue causing severe left ventricular outflow tract obstruction in a post-Senning patient with transposition of the great arteries

Accessory mitral valve tissue is a rare congenital anomaly associated with congenital cardiac defects and is usually detected in the first decade of life. We describe the case of an 18-year old post-Senning asymptomatic patient who was found to have accessory mitral valve tissue on transthoracic echocardiography producing severe left ventricular outflow tract obstruction

Specific gut microbiota features and metabolic markers in postmenopausal women with obesity

BACKGROUND: Gut microbial gene richness and specific bacterial species are associated with metabolic risk markers in humans, but the impact of host physiology and dietary habits on the link between the gut microbiota and metabolic markers remain unclear. The objective of this study was to identify gut metagenomic markers associated with estimates of insulin resistance, lipid metabolism and inflammation in obesity, and to explore whether the associations between metagenomic and metabolic markers persisted after adjustment for body fat, age and habitual dietary intake. METHODS: Faecal DNA from 53 women with obesity was analysed through quantitative metagenomic sequencing and analysis, and a systematic search was performed for bacterial genes associated with estimates of insulin resistance, inflammation and lipid metabolism. Subsequently, the correlations between metagenomic species and metabolic markers were tested by linear regression models, with and without covariate adjustment. RESULTS: One hundred and fourteen metagenomic species correlated with metabolic markers (P<0.001) including Akkermansia muciniphila, Bilophila wadsworthia, Bifidobacterium longum and Faecalibacterium prausnitzii, but also species not previously associated with metabolic markers including Bacteroides faecis and Dorea longicatena. The majority of the identified correlations between bacterial species and metabolic markers persisted after adjustment for differences in body fat, age and dietary macronutrient composition; however, the negative correlation with insulin resistance observed for B. longum and F. prausnitzii appeared to be modified by the intake of dietary fibre and fat, respectively. CONCLUSIONS: This study shows that several gut bacterial species are linked to metabolic risk markers in obesity, also after adjustment for potential confounders, such as long-term diet composition. The study supports the use of gut metagenomic markers for metabolic disease prediction and warrants further investigation of causality

Gamma decay of the 154^{154}Sm Isovector Giant Dipole Resonance: Smekal-Raman Scattering as a Novel Probe of Nuclear Ground-State Deformation

The $\gamma$ decays of the Isovector Giant Dipole Resonance (GDR) of the deformed nucleus $^{154}$Sm from $2^+_1$-Smekal-Raman and elastic scattering were measured using linearly polarized, quasi-monochromatic photon beams. The two scattering processes were disentangled through their distinct angular distributions. Their branching ratio and cross sections were determined at six excitation energies covering the $^{154}$Sm GDR. Both agree with the predictions of the geometrical model for the GDR and establish $\gamma$ decay as an observable sensitive to the structure of the resonance. Consequently, the data place strong constraints on the nuclear shape, including the degree of triaxiality. The derived $^{154}$Sm shape parameters $\beta=0.2926(26)$ and $\gamma=5.0(14)$ agree well with other measurements and recent Monte Carlo Shell-Model calculations.Comment: 7 pages, 3 figures, 3 table

Gamma Decay of the 154Sm Isovector Giant Dipole Resonance: Smekal-Raman Scattering as a Novel Probe of Nuclear Ground-State Deformation

The γ decays of the isovector giant dipole resonance (IVGDR) of the deformed nucleus Sm154 were measured using 21+-Smekal-Raman and elastic scattering of linearly polarized, quasimonochromatic photon beams. The two scattering processes were disentangled through their distinct angular distributions. Their branching ratio and cross sections were determined at six excitation energies covering the Sm154 IVGDR. Both agree with the predictions of the geometrical model for the IVGDR and confirm γ decay as an observable sensitive to the structure of the resonance. Consequently, the data place strong constraints on the nuclear shape, including the degree of triaxiality. The derived Sm154 shape parameters β=0.2925(25) and γ=5.0(15)° agree well with other measurements and recent Monte Carlo shell-model calculations

Adipose tissue pathways involved in weight loss of cancer cachexia

White adipose tissue (WAT) constitutes our most expandable tissue and largest endocrine organ secreting hundreds of polypeptides collectively termed adipokines. Changes in WAT mass induce alterations in adipocyte secretion and function, which are linked to disturbed whole-body metabolism. Although the mechanisms controlling this are not clear they are dependent on changes in gene expression, a complex process which is regulated at several levels. Results in recent years have highlighted the role of small non-coding RNA molecules termed microRNAs (miRNAs), which regulate gene expression via post-transcriptional mechanisms. The aim of this thesis was to characterize global gene expression levels and describe novel miRNAs and adipokines controlling the function of human WAT in conditions with pathological increases or decreases in WAT mass. Obesity and cancer cachexia were selected as two models since they are both clinically relevant and characterized by involuntary changes in WAT mass. In Study I, expressional analyses were performed in subcutaneous WAT from cancer patients with or without cachexia and obese versus non-obese subjects. In total, 425 transcripts were found to be regulated in cancer cachexia. Pathway analyses based on this set of genes revealed that processes involving extracellular matrix, actin cytoskeleton and focal adhesion were significantly downregulated, whereas fatty acid metabolism was upregulated comparing cachectic with weight-stable cancer subjects. Furthermore, by overlapping these results with microarray data from an obesity study, many transcripts were found to be reciprocally regulated comparing the two conditions. This suggests that WAT gene expression in cancer cachexia and obesity are regulated by similar, albeit opposing, mechanisms. In Study II, the focus was on the family of fibroblast growth factors (FGFs), members of which have recently been implicated in the development of obesity and insulin resistance. A retrospective analysis of global gene expression data identified several FGFs (FGF1/2/7/9/13/18) to be expressed in WAT. However, only one, FGF1, was actively secreted from WAT and predominantly so from the adipocyte fraction. Moreover, FGF1 release was increased in obese compared to non-obese subjects, but was not normalized by weight loss. Although the clinical significance of these findings is not yet clear, it can be hypothesized that FGF1 may play a role in WAT growth, possibly by promoting fat cell proliferation and/or differentiation. In Study III, we identified adipose miRNAs regulated in obesity. Out of eleven miRNAs regulated by changes in body fat mass, ten controlled the production of the pro-inflammatory chemoattractant chemokine (C-C motif) ligand 2 (CCL2) when overexpressed in fat cells and for two, miR-126 and -193b, signaling circuits were defined. In Study IV, a novel adipokine, semaphorin 3C (SEMA3C), was identified by combining transcriptome and secretome data. Detailed studies focusing on SEMA3C revealed that this factor was secreted from adipocytes and induced the expression of extracellular matrix and matricellular genes in preadipocytes. Furthermore, SEMA3C mRNA levels correlated with interstitial fibrosis and insulin resistance in WAT derived from subjects with a wide range in BMI. In summary, the results presented in this thesis have delineated transcriptional alterations in WAT in two clinically relevant conditions, obesity and cancer cachexia. This has allowed the identification of novel adipokines and microRNAs with potential pathophysiological importance. These findings form the basis for further studies aiming at understanding the central role of WAT in disorders associated with metabolic complications