Influence of internal flexibility on the double glass transition in a series of odd non-symmetric liquid crystal dimers characterised by dielectric measurements

Dielectric measurements (thermally stimulated depolarisation currents and broadband dielectric spectroscopy) have been performed near the glass transition to study the glass transition on the odd non-symmetric liquid crystal (LC) dimers of the series -(4-cyanobiphenyl-4'-oxy)--(1-pyreniminebenzylidene-4'-oxy) alkanes (CBOnO.Py) with n ranging from 3 to 9. A previous study [S. Diez-Berart et al., Materials 8 (2015) 3334] carried out in CBO11O.Py showed the presence of two glass transition temperatures, attributed to different molecular motions of the terminal groups. The study performed allows us to analyse the molecular dynamics in the rest of the series and determine the role played by the flexible spacer. Parallel and perpendicular orientations of the molecular director with regards to the probe electric field have been investigated. The low and intermediate observed relaxations are explained in the framework of Stocchero's theoretical model [M. Stocchero, J. Chem. Phys. 121 (2004) 8079] for the dielectric behaviour of non-symmetric LCs dimers, as independent end-over-end rotations of each terminal semi-rigid unit. As the length of the spacer chain in the series of compounds decreases, the different relaxations become progressively more coupled at the glass transition. Numerical simulations of the calorimetric response from the obtained kinetic parameters show good agreement with experimental behaviour.Postprint (author's final draft

Overeating, caloric restriction and breast cancer risk by pathologic subtype: the EPIGEICAM study

This study analyzes the association of excessive energy intake and caloric restriction with breast cancer (BC) risk taking into account the individual energy needs of Spanish women. We conducted a multicenter matched case-control study where 973 pairs completed lifestyle and food frequency questionnaires. Expected caloric intake was predicted from a linear regression model in controls, including calories consumed as dependent variable, basal metabolic rate as an offset and physical activity as explanatory. Overeating and caloric restriction were defined taking into account the 99% confidence interval of the predicted value. The association with BC risk, overall and by pathologic subtype, was evaluated using conditional and multinomial logistic regression models. While premenopausal women that consumed few calories (>20% below predicted) had lower BC risk (OR = 0.36; 95% CI = 0.21–0.63), postmenopausal women with an excessive intake (≥40% above predicted) showed an increased risk (OR = 2.81; 95% CI = 1.65–4.79). For every 20% increase in relative (observed/predicted) caloric intake the risk of hormone receptor positive (p-trend < 0.001) and HER2+ (p-trend = 0.015) tumours increased 13%, being this figure 7% for triple negative tumours. While high energy intake increases BC risk, caloric restriction could be protective. Moderate caloric restriction, in combination with regular physical activity, could be a good strategy for BC prevention

A role for Oncostatin M in the impairment of glucose homeostasis in obesity

CONTEXT: Oncostatin M (OSM) plays a key role in inflammation, but its regulation and function during obesity is not fully understood. OBJECTIVE: The aim of this study was to evaluate the relationship of OSM with the inflammatory state that leads to impaired glucose homeostasis in obesity. We also assessed whether OSM immunoneutralization could revert metabolic disturbances caused by a high-fat diet (HFD) in mice. DESIGN: 28 patients with severe obesity were included and stratified into two groups: (1) glucose levels 100 mg/dL. White adipose tissue was obtained to examine OSM gene expression. Human adipocytes were used to evaluate the effect of OSM in the inflammatory response, and HFD-fed C57BL/6J mice were injected with anti-OSM antibody to evaluate its effects. RESULTS: OSM expression was elevated in subcutaneous and visceral fat from patients with obesity and hyperglycemia, and correlated with Glut4 mRNA levels, serum insulin, homeostatic model assessment of insulin resistance, and inflammatory markers. OSM inhibited adipogenesis and induced inflammation in human adipocytes. Finally, OSM receptor knockout mice had increased Glut4 mRNA levels in adipose tissue, and OSM immunoneutralization resulted in a reduction of glucose levels and Ccl2 expression in adipose tissue from HFD-fed mice. CONCLUSIONS: OSM contributes to the inflammatory state during obesity and may be involved in the development of insulin resistance

Adherence to the Western, Prudent and Mediterranean dietary patterns and breast cancer risk: MCC-Spain study

Objective To externally validate the previously identified effect on breast cancer risk of the Western, Prudent and Mediterranean dietary patterns. Study design MCC-Spain is a multicase-control study that collected epidemiological information on 1181 incident cases of female breast cancer and 1682 control cases from 10 Spanish provinces. Three dietary patterns derived in another Spanish case-control study were analysed in the MCC-Spain study. These patterns were termed Western (high intakes of fatty and sugary products and red and processed meat), Prudent (high intakes of low-fat dairy products, vegetables, fruits, whole grains and juices) and Mediterranean (high intake of fish, vegetables, legumes, boiled potatoes, fruits, olives, and vegetable oil, and a low intake of juices). Their association with breast cancer was assessed using logistic regression models with random province-specific intercepts considering an interaction with menopausal status. Risk according to tumour subtypes ? based on oestrogen (ER), progesterone (PR) and human epidermal growth factor 2 (HER2) receptors (ER+/PR+&HER2-; HER2+; ER-/PR-&HER2-) ? was evaluated with multinomial regression models. Main outcome measures Breast cancer and histological subtype. Results Our results confirm most of the associations found in the previous case-control study. A high adherence to the Western dietary pattern seems to increase breast cancer risk in both premenopausal women (OR4thvs.1stquartile(95%CI):1.68(1.02;2.79); OR1SD-increase(95%CI): 1.19(1.01;1.40)) and postmenopausal women (OR4thvs.1stquartile(95%CI):1.48(1.07;2.05); OR1SD-increase(95%CI): 1.14(1.01;1.28)). While high adherence to the Prudent pattern did not show any effect on breast cancer, the Mediterranean dietary pattern seemed to be protective, but only among postmenopausal women (OR4thvs.1stquartile (95%CI):0.72(95% CI 0.53;0.98); p-int = 0.075). There were no significant differences by tumour subtype. Conclusion Dietary recommendations based on a departure from the Western dietary pattern in favour of the Mediterranean diet could reduce breast cancer risk in the general population.The study was funded by Carlos III Institute of Health grants (PI12/00488, PI12/00265, PI12/00715, PI12/01270, PI09/00773 and PI08/1770), by the Spanish Ministry of Economy and Competitiveness (IJCI-2014-20900) and by Consejería de Salud de la Junta de Andalucía (PI-0571- 2009 and PI-0306-2011) competitive calls including peer review for scientific quality. Additional funding was provided by the Spanish Federation of Breast Cancer Patients (FECMA: EPY 1169- 10), the Association of Women with Breast Cancer from Elche (AMACMEC:EPY 1394/15), the Marqués de Valdecilla foundation (grant API 10/09), ) and by Acción Transversal del Cancer, approved by the Spanish Ministry Council on October 11, 2007. None of the funders played any role in conducting research or writing the paper

Trends in incidence, mortality and survival in women with breast cancer from 1985 to 2012 in Granada, Spain: a population-based study

The incidence of breast cancer has increased since the 1970s. Despite favorable trends in prognosis, the role of changes in clinical practice and the introduction of screening remain controversial. We examined breast cancer trends to shed light on their determinants Overall, age-adjusted (European Standard Population) incidence rates increased from 48.0 cases × 100,000 women in 1985–1989 to 83.4 in 2008–2012, with an annual percentage change (APC) of 2.5% (95%CI, 2.1–2.9) for 1985–2012. The greatest increase was in women younger than 40 years (APC 3.5, 95%CI, 2.4–4.8). For 2000–2012 the incidence trend increased only for stage I tumors (APC 3.8, 95%CI, 1.9–5.8). Overall age-adjusted breast cancer mortality decreased (APC − 1, 95%CI, − 1.4 – − 0.5), as did mortality in the 50–69 year age group (APC − 1.3, 95%CI, − 2.2 – − 0.4). Age-standardized net survival increased from 67.5% at 5 years in 1985–1989 to 83.7% in 2010–2012. All age groups younger than 70 years showed a similar evolution. Five-year net survival rates were 96.6% for patients with tumors diagnosed in stage I, 88.2% for stage II, 62.5% for stage III and 23.3% for stage IV. Breast cancer incidence is increasing – a reflection of the evolution of risk factors and increasing diagnostic pressure. After screening was introduced, the incidence of stage I tumors increased, with no decrease in the incidence of more advanced stages. Reductions were seen for overall mortality and mortality in the 50–69 year age group, but no changes were found after screening implementation. Survival trends have evolved favorably except for the 70–84 year age group and for metastatic tumors.This study was supported by a grant from the Acción Estratégica en Salud plan for the High Resolution Project on Prognosis and Care of Cancer Patients (No. AC14/00036) awarded by the Spanish Ministry of Economy and Competitiveness and co-funded by the European Regional Development Fund (ERDF)

Activity of cortical and thalamic neurons during the slow (<1 Hz) rhythm in the mouse in vivo

During NREM sleep and under certain types of anaesthesia, the mammalian brain exhibits a distinctive slow (<1 Hz) rhythm. At the cellular level, this rhythm correlates with so-called UP and DOWN membrane potential states. In the neocortex, these UP and DOWN states correspond to periods of intense network activity and widespread neuronal silence, respectively, whereas in thalamocortical (TC) neurons, UP/DOWN states take on a more stereotypical oscillatory form, with UP states commencing with a low-threshold Ca2+ potential (LTCP). Whilst these properties are now well recognised for neurons in cats and rats, whether or not they are also shared by neurons in the mouse is not fully known. To address this issue, we obtained intracellular recordings from neocortical and TC neurons during the slow (<1 Hz) rhythm in anaesthetised mice. We show that UP/DOWN states in this species are broadly similar to those observed in cats and rats, with UP states in neocortical neurons being characterised by a combination of action potential output and intense synaptic activity, whereas UP states in TC neurons always commence with an LTCP. In some neocortical and TC neurons, we observed ‘spikelets’ during UP states, supporting the possible presence of electrical coupling. Lastly, we show that, upon tonic depolarisation, UP/DOWN states in TC neurons are replaced by rhythmic high-threshold bursting at ~5 Hz, as predicted by in vitro studies. Thus, UP/DOWN state generation appears to be an elemental and conserved process in mammals that underlies the slow (<1 Hz) rhythm in several species, including humans

Operating a full tungsten actively cooled tokamak: overview of WEST first phase of operation

WEST is an MA class superconducting, actively cooled, full tungsten (W) tokamak, designed to operate in long pulses up to 1000 s. In support of ITER operation and DEMO conceptual activities, key missions of WEST are: (i) qualification of high heat flux plasma-facing components in integrating both technological and physics aspects in relevant heat and particle exhaust conditions, particularly for the tungsten monoblocks foreseen in ITER divertor; (ii) integrated steady-state operation at high confinement, with a focus on power exhaust issues. During the phase 1 of operation (2017–2020), a set of actively cooled ITER-grade plasma facing unit prototypes was integrated into the inertially cooled W coated startup lower divertor. Up to 8.8 MW of RF power has been coupled to the plasma and divertor heat flux of up to 6 MW m−2 were reached. Long pulse operation was started, using the upper actively cooled divertor, with a discharge of about 1 min achieved. This paper gives an overview of the results achieved in phase 1. Perspectives for phase 2, operating with the full capability of the device with the complete ITER-grade actively cooled lower divertor, are also described