Ideal cardiovascular health and inflammation in European adolescents: The HELENA study

Background and aims Inflammation plays a key role in atherosclerosis and this process seems to appear in childhood. The ideal cardiovascular health index (ICHI) has been inversely related to atherosclerotic plaque in adults. However, evidence regarding inflammation and ICHI in adolescents is scarce. The aim is to assess the association between ICHI and inflammation in European adolescents. Methods and results As many as 543 adolescents (251 boys and 292 girls) from the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study, a cross-sectional multi-center study including 9 European countries, were measured. C-reactive protein (CRP), complement factors C3 and C4, leptin and white blood cell counts were used to compute an inflammatory score. Multilevel linear models and multilevel logistic regression were used to assess the association between ICHI and inflammation controlling by covariates. Higher ICHI was associated with a lower inflammatory score, as well as with several individual components, both in boys and girls (p < 0.01). In addition, adolescents with at least 4 ideal components of the ICHI had significantly lower inflammatory score and lower levels of the study biomarkers, except CRP. Finally, the multilevel logistic regression showed that for every unit increase in the ICHI, the probability of having an inflammatory profile decreased by 28.1% in girls. Conclusion Results from this study suggest that a better ICHI is associated with a lower inflammatory profile already in adolescence. Improving these health behaviors, and health factors included in the ICHI, could play an important role in CVD prevention

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting

Predictive timing functions of cortical beta oscillations are impaired in Parkinson's disease and influenced by L-DOPA and deep brain stimulation of the subthalamic nucleus

Cortex-basal ganglia circuits participate in motor timing and temporal perception, and are important for the dynamic configuration of sensorimotor networks in response to exogenous demands. In Parkinson's disease (PD) patients, rhythmic auditory stimulation (RAS) induces motor performance benefits. Hitherto, little is known concerning contributions of the basal ganglia to sensory facilitation and cortical responses to RAS in PD. Therefore, we conducted an EEG study in 12 PD patients before and after surgery for subthalamic nucleus deep brain stimulation (STN-DBS) and in 12 age-matched controls. Here we investigated the effects of levodopa and STN-DBS on resting-state EEG and on the cortical-response profile to slow and fast RAS in a passive-listening paradigm focusing on beta-band oscillations, which are important for auditory–motor coupling. The beta-modulation profile to RAS in healthy participants was characterized by local peaks preceding and following auditory stimuli. In PD patients RAS failed to induce pre-stimulus beta increases. The absence of pre-stimulus beta-band modulation may contribute to impaired rhythm perception in PD. Moreover, post-stimulus beta-band responses were highly abnormal during fast RAS in PD patients. Treatment with levodopa and STN-DBS reinstated a post-stimulus beta-modulation profile similar to controls, while STN-DBS reduced beta-band power in the resting-state. The treatment-sensitivity of beta oscillations suggests that STN-DBS may specifically improve timekeeping functions of cortical beta oscillations during fast auditory pacing

Photosynthetic pathway variation among C4 grasses along a precipitation gradient in Argentina

Aim Based on the biochemical and physiological attributes of C4 grasses, and on the close association between decarboxylation pathways and the taxa in which they evolved, the hypotheses tested were: (1) that C4 grasses would become progressively more abundant as precipitation decreased, with grasses of the NADP-me subtype more abundant in wetter sites and those of the NAD-me subtype more common in arid regions; and (2) that the distribution of grass subfamilies would also be correlated with annual precipitation. Location The study was conducted along a precipitation gradient in central Argentina, from the eastern Pampas (>1000 mm year)1 ) to the western deserts and semi-deserts near the Andes (<100 mm year)1 ). Methods Percentage of species and relative cover of C3 and C4 grasses (including C4 subtypes) in local floras from 15 lowland sites of central Argentina were obtained from our own unpublished data and from recently published floristic surveys. Pearson correlation coefficients were obtained between grass distribution parameters and the available climatic data. Results The percentage of C4 grasses increased towards the arid extreme and showed a strong negative correlation with annual rainfall (r = )0.74, P < 0.01). Within the C4 subtypes, the NADP-me species showed a higher proportional representation at the wetter extreme, whereas the representation of NAD-me species increased towards the more arid extreme. The relationship of PEP-ck species with climatic parameters in central Argentina was less evident. The distributions of the Panicoideae and Chloridoideae subfamilies along the precipitation gradient were diametrically opposed, with the Panicoideae positively (r = 0.86, P < 0.001) and the Chloridoideae negatively (r = )0.87, P < 0.001) correlated with annual precipitation. Main conclusions Our data are consistent with the broad observation that C4 grasses tend to dominate in areas where the wet season falls in the warmer summer months. In agreement with previously reported results for Africa, Asia, Australia and North America, we describe here for the first time a significant relationship between annual precipitation and the prevalence of the NADP-me and NAD-me photosynthetic pathways along climatic gradients for the Neotropics. We also report for the first time that correlations between C4 species and annual rainfall are stronger when the relative cover of grass species is considered. The association of grass subfamilies Panicoideae and Chloridoideae with rainfall is as strong as that recorded for the NADP-me and NAD-me variants, respectively, suggesting that characteristics other than decarboxylation type may be responsible for the geographic patterns described in this studyFil: Cabido, Marcelo Ruben. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Pons, Stella Maris. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias; ArgentinaFil: Cantarero, Juan Jose. Universidad Nacional de Río Cuarto. Facultad de Agronomía y Veterinaria; ArgentinaFil: Lewis, Juan Pablo. Universidad Nacional de Rosario. Facultad de Ciencias Agrarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Anton, Ana Maria Ramona. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentin