Weight loss surgery in adolescents corrects high-density lipoprotein subspecies and their function.

Background/objectiveYouth with obesity have an altered high-density lipoprotein (HDL) subspecies profile characterized by depletion of large apoE-rich HDL particles and an enrichment of small HDL particles. The goal of this study was to test the hypothesis that this atherogenic HDL profile is reversible and that HDL function would improve with metabolic surgery.MethodsSerum samples from adolescent males with severe obesity mean±s.d. age of 17.4±1.6 years were studied at baseline and 1 year following vertical sleeve gastrectomy (VSG). HDL subspecies and HDL function were evaluated pre and post VSG using paired t-tests. A lean group of adolescents was included as a reference group.ResultsAfter VSG, body mass index decreased by 32% and insulin resistance as estimated by homeostatic model assessment of insulin resistance decreased by 75% (both P<0.01). Large apoE-rich HDL subspecies increased following VSG (P<0.01) and approached that of lean adolescents despite participants with considerable residual obesity. In addition, HDL function improved compared with baseline (cholesterol efflux capacity increased by 12%, HDL lipid peroxidation potential decreased by 30% and HDL anti-oxidative capacity improved by 25%, all P<0.01).ConclusionsMetabolic surgery results in a significant improvement in the quantity of large HDL subspecies and HDL function. Our data suggest metabolic surgery may improve cardiovascular risk in adolescents and young adults

Systematic review of the role of high intensity focused ultrasound (HIFU) in treating malignant lesions of the hepatobiliary system

BACKGROUND: High Intensity Focused Ultrasound (HIFU) is an emerging non-invasive, targeted treatment of malignancy. The aim of this review was to assess the efficacy, safety and optimal technical parameters of HIFU to treat malignant lesions of the hepatobiliary system. METHODS: A systematic search of the English literature was performed until March 2020, interrogating Pubmed, Embase and Cochrane Library databases. The following key-words were input in various combinations: 'HIFU', 'High intensity focussed ultrasound', 'Hepatobiliary', 'Liver', 'Cancer' and 'Carcinoma'. Extracted content included: Application type, Exposure parameters, Patient demographics, and Treatment outcomes. RESULTS: Twenty-four articles reported on the clinical use of HIFU in 940 individuals to treat malignant liver lesions. Twenty-one studies detailed the use of HIFU to treat hepatocellular carcinoma only. Mean tumour size was 5.1 cm. Across all studies, HIFU resulted in complete tumour ablation in 55% of patients. Data on technical parameters and the procedural structure was very heterogeneous. Ten studies (n = 537 (57%) patients) described the use of HIFU alongside other modalities including TACE, RFA and PEI; 66% of which resulted in complete tumour ablation. Most common complications were skin burns (15%), local pain (5%) and fever (2%). CONCLUSION: HIFU has demonstrated benefit as a treatment modality for malignant lesions of the hepatobiliary system. Combining HIFU with other ablative therapies, particularly TACE, increases the efficacy without increasing complications. Future human clinical studies are required to determine the optimal treatment parameters, better define outcomes and explore the risks and benefits of combination therapies

State Effects of Two Forms of Meditation on Prefrontal EEG Asymmetry in Previously Depressed Individuals

We investigated state effects of two forms of meditation on electroencephalography prefrontal α-asymmetry, a global indicator of approach versus withdrawal motivation and related affective state. A clinical series of previously depressed individuals were guided to practice either mindfulness breathing meditation (N = 8) or a form of meditation directly aimed at cultivating positive affect, loving kindness or metta meditation (N = 7). Prefrontal asymmetry was assessed directly before and after the 15-min meditation period. Results showed changes in asymmetry towards stronger relative left prefrontal activation, i.e., stronger approach tendencies, regardless of condition. Further explorations of these findings suggested that responses were moderated by participants’ tendencies to engage in ruminative brooding. Individuals high in brooding tended to respond to breathing meditation but not loving kindness meditation, while those low in brooding showed the opposite pattern. Comparisons with an additionally recruited “rest” group provided evidence suggesting that changes seen were not simply attributable to habituation. The results indicate that both forms of meditation practice can have beneficial state effects on prefrontal α-asymmetry and point towards differential indications for offering them in the treatment of previously depressed patients

Minimal flavour violation extensions of the seesaw

We analyze the most natural formulations of the minimal lepton flavour violation hypothesis compatible with a type-I seesaw structure with three heavy singlet neutrinos N, and satisfying the requirement of being predictive, in the sense that all LFV effects can be expressed in terms of low energy observables. We find a new interesting realization based on the flavour group $SU(3)_e\times SU(3)_{\ell+N}$ (being $e$ and $\ell$ respectively the SU(2) singlet and doublet leptons). An intriguing feature of this realization is that, in the normal hierarchy scenario for neutrino masses, it allows for sizeable enhancements of $\mu \to e$ transitions with respect to LFV processes involving the $\tau$ lepton. We also discuss how the symmetries of the type-I seesaw allow for a strong suppression of the N mass scale with respect to the scale of lepton number breaking, without implying a similar suppression for possible mechanisms of N productionComment: 14 pages, 6 figure

Perturbations of nuclear C*-algebras

Kadison and Kastler introduced a natural metric on the collection of all C*-subalgebras of the bounded operators on a separable Hilbert space. They conjectured that sufficiently close algebras are unitarily conjugate. We establish this conjecture when one algebra is separable and nuclear. We also consider one-sided versions of these notions, and we obtain embeddings from certain near inclusions involving separable nuclear C*-algebras. At the end of the paper we demonstrate how our methods lead to improved characterisations of some of the types of algebras that are of current interest in the classification programme.Comment: 45 page

In-cell NMR characterization of the secondary structure populations of a disordered conformation of α-Synuclein within E. coli cells

α-Synuclein is a small protein strongly implicated in the pathogenesis of Parkinson’s disease and related neurodegenerative disorders. We report here the use of in-cell NMR spectroscopy to observe directly the structure and dynamics of this protein within E. coli cells. To improve the accuracy in the measurement of backbone chemical shifts within crowded in-cell NMR spectra, we have developed a deconvolution method to reduce inhomogeneous line broadening within cellular samples. The resulting chemical shift values were then used to evaluate the distribution of secondary structure populations which, in the absence of stable tertiary contacts, are a most effective way to describe the conformational fluctuations of disordered proteins. The results indicate that, at least within the bacterial cytosol, α-synuclein populates a highly dynamic state that, despite the highly crowded environment, has the same characteristics as the disordered monomeric form observed in aqueous solution

Dietary garlic and hip osteoarthritis: evidence of a protective effect and putative mechanism of action

Background Patterns of food intake and prevalent osteoarthritis of the hand, hip, and knee were studied using the twin design to limit the effect of confounding factors. Compounds found in associated food groups were further studied in vitro. Methods Cross-sectional study conducted in a large population-based volunteer cohort of twins. Food intake was evaluated using the Food Frequency Questionnaire; OA was determined using plain radiographs. Analyses were adjusted for age, BMI and physical activity. Subsequent in vitro studies examined the effects of allium-derived compounds on the expression of matrix-degrading proteases in SW1353 chondrosarcoma cells. Results Data were available, depending on phenotype, for 654-1082 of 1086 female twins (median age 58.9 years; range 46-77). Trends in dietary analysis revealed a specific pattern of dietary intake, that high in fruit and vegetables, showed an inverse association with hip OA (p = 0.022). Consumption of 'non-citrus fruit' (p = 0.015) and 'alliums' (p = 0.029) had the strongest protective effect. Alliums contain diallyl disulphide which was shown to abrogate cytokine-induced matrix metalloproteinase expression. Conclusions Studies of diet are notorious for their confounding by lifestyle effects. While taking account of BMI, the data show an independent effect of a diet high in fruit and vegetables, suggesting it to be protective against radiographic hip OA. Furthermore, diallyl disulphide, a compound found in garlic and other alliums, represses the expression of matrix-degrading proteases in chondrocyte-like cells, providing a potential mechanism of action

The 10th Biennial Hatter Cardiovascular Institute workshop: cellular protection—evaluating new directions in the setting of myocardial infarction, ischaemic stroke, and cardio-oncology

Due to its poor capacity for regeneration, the heart is particularly sensitive to the loss of contractile cardiomyocytes. The onslaught of damage caused by ischaemia and reperfusion, occurring during an acute myocardial infarction and the subsequent reperfusion therapy, can wipe out upwards of a billion cardiomyocytes. A similar program of cell death can cause the irreversible loss of neurons in ischaemic stroke. Similar pathways of lethal cell injury can contribute to other pathologies such as left ventricular dysfunction and heart failure caused by cancer therapy. Consequently, strategies designed to protect the heart from lethal cell injury have the potential to be applicable across all three pathologies. The investigators meeting at the 10th Hatter Cardiovascular Institute workshop examined the parallels between ST-segment elevation myocardial infarction (STEMI), ischaemic stroke, and other pathologies that cause the loss of cardiomyocytes including cancer therapeutic cardiotoxicity. They examined the prospects for protection by remote ischaemic conditioning (RIC) in each scenario, and evaluated impasses and novel opportunities for cellular protection, with the future landscape for RIC in the clinical setting to be determined by the outcome of the large ERIC-PPCI/CONDI2 study. It was agreed that the way forward must include measures to improve experimental methodologies, such that they better reflect the clinical scenario and to judiciously select combinations of therapies targeting specific pathways of cellular death and injury