Longer duration of obesity is associated with a reduction in urinary angiotensinogen in prepubertal children

Background: We aimed to study the impact of obesity on urinary excretion of angiotensinogen (U-AGT) in prepubertal children, focusing on the duration of obesity and gender. Also, we aimed to evaluate whether plasma angiotensinogen (P-AGT) and hydrogen peroxide (H2O2) play a role in the putative association. Methods: Cross-sectional evaluation of 305 children aged 8–9 years (160 normal weight, 86 overweight, and 59 obese). Anthropometric measurements and 24-h ambulatory blood pressure monitoring were performed. Angiotensinogen (AGT) was determined by a commercial enzyme-linked immunosorbent assay (ELISA) kit and H2O2 by a microplate fluorometric assay. Results: U-AGT and P-AGT levels were similar across body mass index (BMI) groups and between sexes. However, boys who were overweight/obese since the age of 4 years presented lower levels of U-AGT compared with those of normal weight at the same age. In children who were overweight/obese since the age of 4, urinary H2O2 decreased with P-AGT. Conclusions: A higher duration of obesity was associated with decreased U-AGT in boys, thus reflecting decreased intrarenal activity of the renin–angiotensin system. Also, children with a longer duration of obesity showed an inverse association between urinary H2O2 and P-AGT. Future studies should address whether these results reflect an early compensatory mechanism to limit obesity-triggered renal dysfunction.This project was supported by funds from Fundo Europeu de Desenvolvimento Regional (FEDER) from Programa Operacional Factores de Competitividade – COMPETE (FCOMP-01-0124-FEDER-028751), by national funds from the Portuguese Foundation for Science and Technology (FCT) (PTDC/DTP-PIC/0239/2012) and by Calouste Gulbenkian Foundation, that granted the study design and data collection and analysis. Liane Correia-Costa was supported by FCT (grant SFRH/SINTD/95898/2013), Teresa Sousa was supported by FCT and POPH/FSE (EC) (Ciência 2008 and SFRH/BPD/112005) and Franz Schaefer was supported by the ERA-EDTA Research Programme and the KfH Foundation for Preventive Medicine. The Epidemiology Research Unit (EPIUnit) is funded by FCT (UID/DTP/04750/2013)

A poorly mixed mantle transition zone and its thermal state inferred from seismic waves

The abrupt changes in mineralogical properties across the Earth’s mantle transition zone substantially impact convection and thermochemical fluxes between the upper and lower mantle. While the 410-km discontinuity at the top of the mantle transition zone is detected with all types of seismic waves, the 660-km boundary is mostly invisible to underside P-wave reflections (P660P). The cause for this observation is debated. The dissociation of ringwoodite and garnet into lower-mantle minerals both contribute to the ‘660’ visibility; only the garnet reaction favours material exchanges across the discontinuity. Here, we combine large datasets of SS and PP precursors, mineralogical modelling and data-mining techniques to obtain a global thermal map of the mantle transition zone, and explain the lack of P660P visibility. We find that its prevalent absence requires a chemically unequilibrated mantle, and its visibility in few locations is associated with potential temperatures greater than 1,800 K. Such temperatures occur in approximately 0.6% of Earth, indicating that the 660 is dominated by ringwoodite decomposition, which tends to impede mantle flow. We find broad regions with elevated temperatures beneath the Pacific surrounded by major volcanic hotspots, indicating plume retention and ponding of hot materials in the mantle transition zone

Assessment of the proliferative, apoptotic and cellular renovation indices of the human mammary epithelium during the follicular and luteal phases of the menstrual cycle

Introduction During the menstrual cycle, the mammary gland goes through sequential waves of proliferation and apoptosis. in mammary epithelial cells, hormonal and non-hormonal factors regulate apoptosis. To determine the cyclical effects of gonadal steroids on breast homeostasis, we evaluated the apoptotic index ( AI) determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling ( TUNEL) staining in human mammary epithelial cells during the spontaneous menstrual cycle and correlated it with cellular proliferation as determined by the expression of Ki-67 during the same period.Methods Normal breast tissue samples were obtained from 42 randomly selected patients in the proliferative ( n = 21) and luteal ( n = 21) phases. Menstrual cycle phase characterization was based on the date of the last and subsequent menses, and on progesterone serum levels obtained at the time of biopsy.Results the proliferation index ( PI), defined as the number of Ki-67-positive nuclei per 1,000 epithelial cells, was significantly larger in the luteal phase (30.46) than in the follicular phase (13.45; P = 0.0033). the AI was defined as the number of TUNEL-positive cells per 1,000 epithelial cells. the average AI values in both phases of the menstrual cycle were not statistically significant ( P = 0.21). However, the cell renewal index ( CRI = PI/AI) was significantly higher in the luteal phase ( P = 0.033). A significant cyclical variation of PI, AI and CRI was observed. PI and AI peaks occurred on about the 24th day of the menstrual cycle, whereas the CRI reached higher values on the 28th day.Conclusions We conclude that proliferative activity is dependent mainly on hormonal fluctuations, whereas apoptotic activity is probably regulated by hormonal and non-hormonal factors.Universidade Federal de São Paulo, Dept Gyneol, Mastol Div, São Paulo, BrazilStanford Univ, Sch Med, Dept Neurosurg, Stanford, CA 94305 USAAPC Pathol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Gyneol, Mastol Div, São Paulo, BrazilWeb of Scienc

f(R) theories

Over the past decade, f(R) theories have been extensively studied as one of the simplest modifications to General Relativity. In this article we review various applications of f(R) theories to cosmology and gravity - such as inflation, dark energy, local gravity constraints, cosmological perturbations, and spherically symmetric solutions in weak and strong gravitational backgrounds. We present a number of ways to distinguish those theories from General Relativity observationally and experimentally. We also discuss the extension to other modified gravity theories such as Brans-Dicke theory and Gauss-Bonnet gravity, and address models that can satisfy both cosmological and local gravity constraints.Comment: 156 pages, 14 figures, Invited review article in Living Reviews in Relativity, Published version, Comments are welcom

Impact of physical activity on redox status and nitric oxide bioavailability in nonoverweight and overweight/obese prepubertal children

Nutritional status might contribute to variations induced by physical activity (PA) in redox status biomarkers. We investigated the influence of PA on redox status and nitric oxide (NO) production/metabolism biomarkers in nonoverweight and overweight/obese prepubertal children. We performed a cross-sectional evaluation of 313 children aged 8-9 years (163 nonoverweight, 150 overweight/obese) followed since birth in a cohort study (Generation XXI, Porto, Portugal). Plasma total antioxidant status (P-TAS), plasma and urinary isoprostanes (P-Isop, U-Isop), urinary hydrogen peroxide (U-H2O2), myeloperoxidase (MPO) and plasma and urinary nitrates and nitrites (P-NOx, U-NOx) were assessed, as well as their association with variables of reported PA quantification (categories of PA frequency (>1x/week and ≤1x/week)and continuous PA index (obtained by the sum of points)) in a questionnaire with increasing ranks from sedentary to vigorous activity levels. U-NOx was significantly higher in children who presented higher PA index scores and higher PA frequency. Separately by BMI classes, U-NOx was significantly higher only in nonoverweight children who practiced PA more frequently (p = 0.037). In overweight/obese children, but not in nonoverweight, P-TAS was higher among children with higher PA frequency (p = 0.007). Homeostasis model assessment index (HOMA-IR) was significantly lower in more active overweight/obese children, but no differences were observed in nonoverweight children. In the fully adjusted multivariate linear regression models for P-TAS, in the overweight/obese group, children with higher PA frequency presented higher P-TAS. In the U-NOx models, U-NOx significantly increased with PA index, only in nonoverweight children. Our results provide additional evidence in support of a protective effect of physical activity, in nonoverweight by increasing NO bioavailability and in overweight/obese children by enhancing systemic antioxidant capacity and insulin sensitivity. These results highlight the importance of engaging in regular physical exercise, particularly among overweight/obese children, in which a positive association between oxidant status and cardiometabolic risk markers has been described.This project was supported by FEDER funds from Programa Operacional Factores de Competitividade – COMPETE [FCOMP-01-0124-FEDER-028751], by national funds from the Portuguese Foundation for Science and Technology (FCT), Lisbon, Portugal [PTDC/DTP-PIC/0239/2012] and by Calouste Gulbenkian Foundation. Liane Correia-Costa was supported by FCT [SFRH/SINTD/95898/2013] and Teresa Sousa was supported by FCT and POPH/FSE (EC) [Ciência 2008 and SFRH/BPD/112005]

S100B as a potential biomarker and therapeutic target in multiple sclerosis

Multiple sclerosis (MS) pathology is characterized by neuroinflammation and demyelination. Recently, the inflammatory molecule S100B was identified in cerebrospinal fluid (CSF) and serum of MS patients. Although seen as an astrogliosis marker, lower/physiological levels of S100B are involved in oligodendrocyte differentiation/maturation. Nevertheless, increased S100B levels released upon injury may induce glial reactivity and oligodendrocyte demise, exacerbating tissue damage during an MS episode or delaying the following remyelination. Here, we aimed to unravel the functional role of S100B in the pathogenesis of MS. Elevated S100B levels were detected in the CSF of relapsing-remitting MS patients at diagnosis. Active demyelinating MS lesions showed increased expression of S100B and its receptor, the receptor for advanced glycation end products (RAGE), in the lesion area, while chronic active lesions displayed increased S100B in demyelinated areas with lower expression of RAGE in the rim. Interestingly, reactive astrocytes were identified as the predominant cellular source of S100B, whereas RAGE was expressed by activated microglia/macrophages. Using an ex vivo demyelinating model, cerebral organotypic slice cultures treated with lysophosphatidylcholine (LPC), we observed a marked elevation of S100B upon demyelination, which co-localized mostly with astrocytes. Inhibition of S100B action using a directed antibody reduced LPC-induced demyelination, prevented astrocyte reactivity and abrogated the expression of inflammatory and inflammasome-related molecules. Overall, high S100B expression in MS patient samples suggests its usefulness as a diagnostic biomarker for MS, while the beneficial outcome of its inhibition in our demyelinating model indicates S100B as an emerging therapeutic target in MS.This work was supported by Medal of Honor L’Oréal for Women in Science (FCT, UNESCO, L’Óreal) and innovation grant (Ordem dos Farmacêuticos) to AF, a post-doctoral grant from Fundação para a Ciência e Tecnologia (FCT-SFRH/BPD/96794/2013) and a DuPré Grant from the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) to AB, and by FCT-Pest- OE/SAU/UI4013 to iMed.ULisboa.info:eu-repo/semantics/publishedVersio

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Constrained pre-equalization accounting for multi-path fading emulated using large RC networks: applications to wireless and photonics communications

Multi-path propagation is modelled assuming a multi-layer RC network with randomly allocated resistors and capacitors to represent the transmission medium. Due to frequency-selective attenuation, the waveforms associated with each propagation path incur path-dependent distortion. A pre-equalization procedure that takes into account the capabilities of the transmission source as well as the transmission properties of the medium is developed. The problem is cast within a Mixed Integer Linear Programming optimization framework that uses the developed nominal RC network model, with the excitation waveform customized to optimize signal fidelity from the transmitter to the receiver. The objective is to match a Gaussian pulse input accounting for frequency regions where there would be pronounced fading. Simulations are carried out with different network realizations in order to evaluate the sensitivity of the solution with respect to changes in the transmission medium mimicking the multi-path propagation. The proposed approach is of relevance where equalization techniques are difficult to implement. Applications are discussed within the context of emergent communication modalities across the EM spectrum such as light percolation as well as emergent indoor communications assuming various modulation protocols or UWB schemes as well as within the context of space division multiplexing

Strength training to prevent falls in older adults: A systematic review with meta-analysis of randomized controlled trials

We performed a systematic review with meta-analysis of randomized controlled trials (RCTs) to assess the effects of strength training (ST), as compared to alternative multimodal or unimodal exercise programs, on the number of falls in older adults (=60 years). Ten databases were consulted (CINAHL, Cochrane Library, EBSCO, EMBASE, PEDro, PubMed, Scielo, Scopus, SPORTDiscus and Web of Science), without limitations on language or publication date. Eligibility criteria were as follows: RCTs with humans =60 years of age of any gender with one group performing supervised ST and a group performing another type of exercise training, reporting data pertaining falls. Certainty of evidence was assessed with Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Meta-analysis used a random effects model to calculate the risk ratio (RR) for number of falls. Five RCTs with six trials were included (n = 543, 76% women). There was no difference between ST and alternative exercise interventions for falls (RR = 1.00, 95% CI 0.77–1.30, p = 0.99). The certainty of evidence was very low. No dose–response relationship could be established. In sum, ST showed comparable RR based on number of falls in older adults when compared to other multimodal or unimodal exercise modalities, but evidence is scarce and heteroge-neous, and additional research is required for more robust conclusions. Registration: PROSPERO CRD42020222908

Oxidative stress and nitric oxide are increased in obese children and correlate with cardiometabolic risk and renal function

Oxidative stress and nitric oxide (NO) appear to represent important links between obesity and cardiovascular, metabolic and/or renal disease. We investigated whether oxidative stress and NO production/metabolism are increased in overweight and obese prepubertal children and correlate with cardiometabolic risk and renal function. We performed a cross-sectional evaluation of 313 children aged 8-9 years. Anthropometrics, 24-h ambulatory blood pressure, pulse wave velocity (PWV), insulin resistance (homoeostasis model assessment index (HOMA-IR)), inflammatory/metabolic biomarkers, estimated glomerular filtration rate (eGFR), plasma total antioxidant status (TAS), plasma and urinary isoprostanes (P-Isop, U-Isop), urinary hydrogen peroxide (U-H2O2), and plasma and urinary nitrates and nitrites (P-NOx, U-NOx) were compared among normal weight, overweight and obese groups, according to WHO BMI z-score reference. U-Isop were increased in the obese group, whereas U-NOx were increased in both overweight and obese children. U-Isop were positively correlated with U-H2O2, myeloperoxidase (MPO), high-sensitivity C-reactive protein, HOMA-IR and TAG. TAS correlated negatively with U-Isop and MPO and positively with PWV. HOMA-IR and U-H2O2 were associated with higher U-Isop, independently of BMI and eGFR, and total cholesterol and U-H2O2 were associated with U-NOx, independently of BMI, eGFR values and P-NOx concentration. In overweight and obese children, eGFR decreased across P-NOx tertiles (median: 139·3 (25th, 75th percentile 128·0, 146·5), 128·0 (25th, 75th percentile 121·5, 140·4), 129·5 (25th, 75th percentile 119·4, 138·3), P for linear trend=0·003). We conclude that oxidant status and NO are increased in relation to fat accumulation and, even in young children, they translate into higher values of cardiometabolic risk markers and affect renal function