The magnitude of nephron number reduction mediates intrauterine growth-restriction-induced long term chronic renal disease in the rat. A comparative study in two experimental models.

Intrauterine growth restriction (IUGR) is a risk factor for hypertension (HT) and chronic renal disease (CRD). A reduction in the nephron number is proposed to be the underlying mechanism; however, the mechanism is debated. The aim of this study was to demonstrate that IUGR-induced HT and CRD are linked to the magnitude of nephron number reduction, independently on its cause. Systolic blood pressure (SBP), glomerular filtration rate (GFR), proteinuria, nephron number, and glomerular sclerosis were compared between IUGR offspring prenatally exposed to a maternal low-protein diet (9% casein; LPD offspring) or maternal administration of betamethasone (from E17 to E19; BET offspring) and offspring with a normal birth weight (NBW offspring). Both prenatal interventions led to IUGR and a similar reduction in birth weight. In comparison to NBW offspring, BET offspring had a severe nephron deficit (-50% in males and -40% in females, p < 0.01), an impaired GFR (-33%, p < 0.05), and HT (SBP+ 17 mmHg, p < 0.05). Glomerular sclerosis was more than twofold higher in BET offspring than in NBW offspring (p < 0.05). Long-term SBP, GFR, and glomerular sclerosis were unchanged in LPD offspring while the nephron number was moderately reduced only in males (-28% vs. NBW offspring, p < 0.05). In this study, the magnitude of nephron number reduction influences long term renal disease in IUGR offspring: a moderate nephron number is an insufficient factor. Extremely long-term follow-up of adults prenatally exposed to glucocorticoids are required

Long-term impact of maternal high-fat diet on offspring cardiac health: role of micro-RNA biogenesis.

Heart failure is a worldwide leading cause of death. Diet and obesity are particularly of high concern in heart disease etiology. Gravely, altered nutrition during developmental windows of vulnerability can have long-term impact on heart health; however, the underlying mechanisms are poorly understood. In the understanding of the initiation of chronic diseases related to developmental exposure to environmental challenges, deregulations in epigenetic mechanisms including micro-RNAs have been proposed as key events. In this context, we aimed at delineating the role of micro-RNAs in the programming of cardiac alterations induced by early developmental exposure to nutritional imbalance. To reach our aim, we developed a human relevant model of developmental exposure to nutritional imbalance by maternally exposing rat to high-fat diet during gestation and lactation. In this model, offspring exposed to maternal high-fat diet developed cardiac hypertrophy and increased extracellular matrix depot compared to those exposed to chow diet. Microarray approach performed on cardiac tissue allowed the identification of a micro-RNA subset which was down-regulated in high-fat diet-exposed animals and which were predicted to regulate transforming growth factor-beta (TGFβ)-mediated remodeling. As indicated by in vitro approaches and gene expression measurement in the heart of our animals, decrease in DiGeorge critical region 8 (DGCR8) expression, involved in micro-RNA biogenesis, seems to be a critical point in the alterations of the micro-RNA profile and the TGFβ-mediated remodeling induced by maternal exposure to high-fat diet. Finally, increasing DGCR8 activity and/or expression through hemin treatment in vitro revealed its potential in the rescue of the pro-fibrotic phenotype in cardiomyocytes driven by DGCR8 decrease. These findings suggest that cardiac alterations induced by maternal exposure to high-fat diet is related to abnormalities in TGFβ pathway and associated with down-regulated micro-RNA processing. Our study highlighted DGCR8 as a potential therapeutic target for heart diseases related to early exposure to dietary challenge

Multiple aspect trajectories: A case study on fishing vessels in the northern adriatic sea

In this paper we build, implement and analyze a spatio-temporal database describing the fishing activities in the Northern Adriatic Sea over four years. The database results from the fusion of two complementary data sources: trajectories from fishing vessels (obtained from terrestrial Automatic Identification System, or AIS, data feed) and the corresponding fish catch reports (i.e., the quantity and type of fish caught). We present all the phases of the dataset creation, starting from the raw data and proceeding through data exploration, data cleaning, trajectory reconstruction and semantic enrichment. Moreover, we formalise and compare different techniques to distribute the fish caught by the fishing vessels along their trajectories. We implement the database with MobilityDB, an open source geospatial trajectory data management and analysis platform. Subsequently, guided by our ecological experts, we perform some analyses on the resulting spatio-temporal database, with the goal of mapping the fishing activities on some key species, highlighting all the interesting information and inferring new knowledge that will be useful for fishery management

Advanced concepts and methods for very high intensity accelerators

AbstractFor very high intensity accelerators, not only beam power but also space charge is a concern. Both aspects should be taken into consideration for any analysis of accelerators aiming at comparing their performances and pointing out the challenging sections. As high beam power is an issue from the lowest energy, careful and exhaustive beam loss predictions have to be done. High space charge implies lattice compactness making the implementation of beam diagnostics very problematic, so a clear strategy for beam diagnostic has to be defined. Beam halo is no longer negligible. Its dynamics is different from that of the core and plays a significant role in the particle loss process. Therefore, beam optimization must take the halo into account and beam characterization must be able to describe the halo part in addition to the core one. This paper presents the advanced concepts and methods for beam analysis, beam loss prediction, beam optimization, beam diagnostic, and beam characterization especially dedicated to very high intensity accelerators. Examples of application of these concepts are given in the case of the IFMIF accelerators

Three-points interfacial quadrature for geometrical source terms on nonuniform grids

International audienceThis paper deals with numerical (finite volume) approximations, on nonuniform meshes, for ordinary differential equations with parameter-dependent fields. Appropriate discretizations are constructed over the space of parameters, in order to guarantee the consistency in presence of variable cells' size, for which $L^p$-error estimates, $1\le p < +\infty$, are proven. Besides, a suitable notion of (weak) regularity for nonuniform meshes is introduced in the most general case, to compensate possibly reduced consistency conditions, and the optimality of the convergence rates with respect to the regularity assumptions on the problem's data is precisely discussed. This analysis attempts to provide a basic theoretical framework for the numerical simulation on unstructured grids (also generated by adaptive algorithms) of a wide class of mathematical models for real systems (geophysical flows, biological and chemical processes, population dynamics)

Influence of clinical and gait analysis experience on reliability of observational gait analysis (Edinburgh Gait Score Reliability)

AbstractObjectivesTreatment complexity of cerebral palsy (CP) patients imposes outcome evaluation studies, which may include objective technical analysis and more subjective functional evaluation. The Edinburgh Gait Score (EGS) was proposed as an additive or alternative when complex instrumented three-dimensional gait analysis is not available. Our purposes were to apply a translated EGS to standard video recordings of independent walking spastic diplegic CP patients, to evaluate its intraobserver and interobserver reliability with respect to gait analysis familiar and not familiar observers.MethodsTen standard video recordings acquired during routine clinical gait analysis were examined by eight observers gait analysis interpretation experienced or not, out of various specialities, two times with a two weeks interval. Kappa statistics and intraclass correlation coefficient were calculated.ResultsBetter reliability was observed for foot and knee scores than in proximal segments with significant differences between stance and swing phase. Significantly better results in gait analysis trained observers underlines the importance to either be used to clinical gait analysis interpretation, or to benefit of video analysis training before observational scoring.ConclusionVisual evaluation may be used for outcome studies to explore clinical changes in CP patients over time and may be associated to other validated evaluation tools

Clinical correlations between lumbar superficial veins and Batson's epidural plexus congestion in chronic low back pain: analysis of two case reports.

Batson's epidural venous plexus plays a crucial role for the generation of vascular back pain, in particular in those conditions characterized by venous congestion, such as heart failure or pregnancy. Except some rudimentary cuspids, the vertebral venous system is considered to be a valveless anastomotic system; as a result the blood is supposed to flow in either direction depending on changes of cardiovascular conditions during the day. Within the narrow boundaries of the neural canal, the epidural veins can therefore get congested, inducing low back pain. The aim of this case report was to highlight a correlation between lumbar superficial veins in patients with chronic low back pain and epidural deep venous plexus congestion. The patients selected underwent a morphologic examination of venous epidural plexus (included its connections with lumbar superficial blood vessels) through a 3D dynamic contrast-enhanced Magnetic Resonance Angiography. The Authors found two different radiological behaviours: total and partial congestion of the vertebral deep venous system. Clinical consequences were discussed and therapeutic strategies were suggested

Thyroid hormone receptor binding to DNA and T(3)-dependent transcriptional activation are inhibited by uremic toxins

BACKGROUND: There is a substantial clinical overlap between chronic renal failure (CRF) and hypothyroidism, suggesting the presence of hypothyroidism in uremic patients. Although CRF patients have low T(3 )and T(4 )levels with normal thyroid-stimulating hormone (TSH), they show a higher prevalence of goiter and evidence for blunted tissue responsiveness to T(3 )action. However, there are no studies examining whether thyroid hormone receptors (TRs) play a role in thyroid hormone dysfunction in CRF patients. To evaluate the effects of an uremic environment on TR function, we investigated the effect of uremic plasma on TRβ1 binding to DNA as heterodimers with the retinoid X receptor alpha (RXRα) and on T(3)-dependent transcriptional activity. RESULTS: We demonstrated that uremic plasma collected prior to hemodialysis (Pre-HD) significantly reduced TRβ1-RXRα binding to DNA. Such inhibition was also observed with a vitamin D receptor (VDR) but not with a peroxisome proliferator-activated receptor gamma (PPARγ). A cell-based assay confirmed this effect where uremic pre-HD ultrafiltrate inhibited the transcriptional activation induced by T(3 )in U937 cells. In both cases, the inhibitory effects were reversed when the uremic plasma and the uremic ultrafiltrate were collected and used after hemodialysis (Post-HD). CONCLUSION: These results suggest that dialyzable toxins in uremic plasma selectively block the binding of TRβ1-RXRα to DNA and impair T(3 )transcriptional activity. These findings may explain some features of hypothyroidism and thyroid hormone resistance observed in CRF patients

From multiple aspect trajectories to predictive analysis: a case study on fishing vessels in the Northern Adriatic sea

In this paper we model spatio-temporal data describing the fishing activities in the Northern Adriatic Sea over four years. We build, implement and analyze a database based on the fusion of two complementary data sources: trajectories from fishing vessels (obtained from terrestrial Automatic Identification System, or AIS, data feed) and fish catch reports (i.e., the quantity and type of fish caught) of the main fishing market of the area. We present all the phases of the database creation, starting from the raw data and proceeding through data exploration, data cleaning, trajectory reconstruction and semantic enrichment. We implement the database by using MobilityDB, an open source geospatial trajectory data management and analysis platform. Subsequently, we perform various analyses on the resulting spatio-temporal database, with the goal of mapping the fishing activities on some key species, highlighting all the interesting information and inferring new knowledge that will be useful for fishery management. Furthermore, we investigate the use of machine learning methods for predicting the Catch Per Unit Effort (CPUE), an indicator of the fishing resources exploitation in order to drive specific policy design. A variety of prediction methods, taking as input the data in the database and environmental factors such as sea temperature, waves height and Clorophill-a, are put at work in order to assess their prediction ability in this field. To the best of our knowledge, our work represents the first attempt to integrate fishing ships trajectories derived from AIS data, environmental data and catch data for spatio-temporal prediction of CPUE – a challenging task