Relationship between oral health and Fried's frailty criteria in community-dwelling older persons.

Oral health and frailty might be linked through several pathways, but previous studies are scarce. This study examined the association between oral health and components of Fried's frailty phenotype. This cross-sectional analysis was based on a sample of 992 community-dwelling persons aged 73 to 77 years observed in the 2011 follow-up of the Lausanne 65+ cohort (Lc65+) study. Data were collected through annual mailed questionnaires, interview and physical examination. Oral health was assessed according to self-reported oral pain and masticatory ability. Frailty was defined as meeting at least one criterion of the Fried's phenotype. Oral pain was reported by 14.8% and chewing problems by 9.7%. Impaired masticatory ability (IMA) was more frequent in subjects with missing teeth or removable dentures (13.5%) than among those with full dentition or fixed dental prostheses (3.2%). In logistic regression analyses adjusting for demographics, alcohol consumption, smoking, comorbidity and financial difficulties, persons with oral pain and those with chewing problems had significantly higher odds of being frail (adjusted OR javax.xml.bind.JAXBElement@4700992c  = 1.72; 95% CI 1.17-2.53 and adjOR javax.xml.bind.JAXBElement@a67b3e3 1.70; 1.07-2.72, respectively). Lack of endurance was associated with both oral pain (adjOR = 3.61; 1.92-6.76) and impaired masticatory ability (adjOR = 2.20; 1.03-4.72). The latter was additionally linked to low physical activity (adjOR = 2.35; 1.29-4.28) and low gait speed (adjOR = 3.12; 1.41-6.90), whereas oral pain was associated with weight loss (adjOR = 1.80; 1.09-2.96) and low handgrip strength (adjOR = 1.80; 1.17-2.77). Self-reported oral pain and chewing impairment had a significant relation with frailty and its components, not only through a nutritional pathway of involuntary weight loss. Longitudinal analyses are needed to examine whether a poor oral condition might be a risk factor for the onset of frailty

Determinants of quality of life in community-dwelling older adults: comparing three cut-offs on the excellent-to-poor spectrum.

The aim of this study was to identify modifications in health, economic and social determinants of quality of life (QoL) in community-dwelling older adults when using different cut-offs to defining favorable QoL. Data of year 2011 annual assessment in 1003 older men and women from the Lc65+ cohort study were used. Overall QoL was self-rated as 'excellent,' 'very good,' 'good,' 'fair,' or 'poor.' To identify significant health (self-rated health, SF-12v2 physical and mental health), economic (financial situation), and social (living with others, being socially supported, emotional support, group activities participation) determinants of QoL, a cut-off was set at three different positions to define favorable QoL on the 'excellent' to 'poor' spectrum: at least 'good' (model 1); at least 'very good' (model 2); and 'excellent' only (model 3). In all three models, bivariable analyses indicated significant associations between QoL and at least one variable from each health, economic, and social dimension. In multivariable analyses, only health-related variables remained significantly associated with QoL in model 1. Model 3 additionally retained financial situation. In model 2, QoL was positively associated with physical health [odds ratio (OR) 1.10, p < 0.001], mental health (OR 1.12, p < 0.001), self-rated health (OR 2.43, p < 0.001), group activities participation (OR 1.43, p = 0.037), being socially supported (OR 1.58, p = 0.024), and not reporting financial difficulties (OR 1.76; p = 0.036). Using different cut-offs to defining favorable QoL results in important changes in the number and type of significant health, economic and social determinants. A cut-off between 'good' and 'very good' appears to best reflect the multidimensional nature of QoL

2D continuous spectrum of shear Alfven waves in the presence of a magnetic island

The radial structure of the continuous spectrum of shear Alfven modes is calculated in the presence of a magnetic island in tokamak plasmas. Modes with the same helicity of the magnetic island are considered in a slab model approximation. In this framework, with an appropriate rotation of the coordinates the problem reduces to 2 dimensions. Geometrical effects due to the shape of the flux surface's cross section are retained to all orders. On the other hand, we keep only curvature effects responsible of the beta induced gap in the low-frequency part of the continuous spectrum. New continuum accumulation points are found at the O-point of the magnetic island. The beta-induced Alfven Eigenmodes (BAE) continuum accumulation point is found to be positioned at the separatrix flux surface. The most remarkable result is the nonlinear modification of the BAE continuum accumulation point frequency

A dual role for Hdac1 : oncosuppressor in tumorigenesis, oncogene in tumor maintenance

Aberrant recruitment of histone deacetylases (HDACs) by the oncogenic fusion protein PML-RAR is involved in the pathogenesis of acute promyelocytic leukemia (APL). PML-RAR, however, is not sufficient to induce disease in mice, but requires additional oncogenic lesions during the pre-leukemic phase. Here, we show that knock-down of Hdac1 and Hdac2 dramatically accelerates leukemogenesis in transgenic pre-leukemic mice. These events are not restricted to APL, since lymphomagenesis driven by deletion of p53, or to a lesser extent by c-myc overexpression, was also accelerated by Hdac1 knock-down. In the pre-leukemic phase of APL Hdac1 counter-acts the activity of PML-RAR in: i) blocking differentiation, ii) impairing genomic stability and iii) increasing self-renewal in hematopoietic progenitors as all of these events are affected by the reduction in Hdac1 levels. This led to an expansion of a subpopulation of PML-RAR expressing cells that is the major source of leukemic stem cells in the full leukemic stage. Remarkably, short-term treatment of pre-leukemic mice with an HDAC inhibitor accelerated leukemogenesis. In contrast, knock-down of Hdac1 in APL mice led to enhanced survival of the leukemic animals. Thus, Hdac1 has a dual role in tumorigenesis: oncosuppressive in the early stages, and oncogenic in established tumor cells

Current drive at plasma densities required for thermonuclear reactors

Progress in thermonuclear fusion energy research based on deuterium plasmas magnetically confined in toroidal tokamak devices requires the development of efficient current drive methods. Previous experiments have shown that plasma current can be driven effectively by externally launched radio frequency power coupled to lower hybrid plasma waves. However, at the high plasma densities required for fusion power plants, the coupled radio frequency power does not penetrate into the plasma core, possibly because of strong wave interactions with the plasma edge. Here we show experiments performed on FTU (Frascati Tokamak Upgrade) based on theoretical predictions that nonlinear interactions diminish when the peripheral plasma electron temperature is high, allowing significant wave penetration at high density. The results show that the coupled radio frequency power can penetrate into high-density plasmas due to weaker plasma edge effects, thus extending the effective range of lower hybrid current drive towards the domain relevant for fusion reactors

Multi-Level Interactions between the Nuclear Receptor TRα1 and the WNT Effectors β-Catenin/Tcf4 in the Intestinal Epithelium

Intestinal homeostasis results from complex cross-regulation of signaling pathways; their alteration induces intestinal tumorigenesis. Previously, we found that the thyroid hormone nuclear receptor TRα1 activates and synergizes with the WNT pathway, inducing crypt cell proliferation and promoting tumorigenesis. Here, we investigated the mechanisms and implications of the cross-regulation between these two pathways in gut tumorigenesis in vivo and in vitro. We analyzed TRα1 and WNT target gene expression in healthy mucosae and tumors from mice overexpressing TRα1 in the intestinal epithelium in a WNT-activated genetic background (vil-TRα1/Apc mice). Interestingly, increased levels of β-catenin/Tcf4 complex in tumors from vil-TRα1/Apc mice blocked TRα1 transcriptional activity. This observation was confirmed in Caco2 cells, in which TRα1 functionality on a luciferase reporter-assay was reduced by the overexpression of β-catenin/Tcf4. Moreover, TRα1 physically interacted with β-catenin/Tcf4 in the nuclei of these cells. Using molecular approaches, we demonstrated that the binding of TRα1 to its DNA target sequences within the tumors was impaired, while it was newly recruited to WNT target genes. In conclusion, our observations strongly suggest that increased β-catenin/Tcf4 levels i) correlated with reduced TRα1 transcriptional activity on its target genes and, ii) were likely responsible for the shift of TRα1 binding on WNT targets. Together, these data suggest a novel mechanism for the tumor-promoting activity of the TRα1 nuclear receptor

Corrigendum: Current drive at plasma densities required for thermonuclear reactors

Nature Communications 1: Article number: 55 (2010); Published: 10 August 2010; Updated:19 September 2013. In Fig. 3 of this Article, the colours of the blue and green curves were accidentally interchanged while the manuscript was being revised. In addition, the x axis labels on Fig. 4 should have read 'Frequency (MHz)'

Overview of the FTU results

Since the 2016 IAEA Fusion Energy Conference, FTU operations have been mainly devoted to experiments on runaway electrons and investigations into a tin liquid limiter; other experiments have involved studies of elongated plasmas and dust. The tearing mode onset in the high density regime has been studied by means of the linear resistive code MARS, and the highly collisional regimes have been investigated. New diagnostics, such as a runaway electron imaging spectroscopy system for in-flight runaway studies and a triple Cherenkov probe for the measurement of escaping electrons, have been successfully installed and tested, and new capabilities of the collective Thomson scattering and the laser induced breakdown spectroscopy diagnostics have been explored