Pulmonary Hypertension and Indicators of Right Ventricular Function.

Pulmonary hypertension (PH) is a rare disease, whose underlying mechanisms are not fully understood. It is characterized by pulmonary arterial vasoconstriction and vessels wall thickening, mainly intimal and medial layers. Several molecular pathways have been studied, but their respective roles remain unknown. Cardiac repercussions of PH are hypertrophy, dilation, and progressive right ventricular dysfunction. Multiple echocardiographic parameters are being used, in order to assess anatomy and cardiac function, but there are no guidelines edited about their usefulness. Thus, it is now recommended to associate the best-known parameters, such as atrial and ventricular diameters or tricuspid annular plane systolic excursion. Cardiac catheterization remains necessary to establish the diagnosis of PH and to assess pulmonary hemodynamic state. Concerning energetic metabolism, free fatty acids, normally used to provide energy for myocardial contraction, are replaced by glucose uptake. These abnormalities are illustrated by increased (18)F-fluorodeoxyglucose ((18)F-FDG) uptake on positron emission tomography/computed tomography, which seems to be correlated with echocardiographic and hemodynamic parameters

Urinary miRNA profiles discriminate between obstruction-induced bladder dysfunction and healthy controls.

Urgency, frequency and incomplete emptying are the troublesome symptoms often shared between benign prostatic obstruction-induced (BLUTD) and neurogenic (NLUTD) lower urinary tract dysfunction. Previously, using bladder biopsies, we suggested a panel of miRNA biomarkers for different functional phenotypes of the bladder. Urine is a good source of circulating miRNAs, but sex- and age-matched controls are important for urinary metabolite comparison. In two groups of healthy subjects (average age 32 and 57 years old, respectively) the total protein and RNA content was very similar between age groups, but the number of secreted extracellular vesicles (uEVs) and expression of several miRNAs were higher in the young healthy male volunteers. Timing of urine collection was not important for these parameters. We also evaluated the suitability of urinary miRNAs for non-invasive diagnosis of bladder outlet obstruction (BOO). A three urinary miRNA signature (miR-10a-5p, miR-301b-3p and miR-363-3p) could discriminate between controls and patients with LUTD (BLUTD and NLUTD). This panel of representative miRNAs can be further explored to develop a non-invasive diagnostic test for BOO. The age-related discrepancy in the urinary miRNA content observed in this study points to the importance of selecting appropriate, age-matched controls

Impact of respiratory motion correction and spatial resolution on lesion detection in PET: a simulation study based on real MR dynamic data

The aim of this study is to investigate the impact of respiratory motion correction and spatial resolution on lesion detectability in PET as a function of lesion size and tracer uptake. Real respiratory signals describing different breathing types are combined with a motion model formed from real dynamic MR data to simulate multiple dynamic PET datasets acquired from a continuously moving subject. Lung and liver lesions were simulated with diameters ranging from 6 to 12 mm and lesion to background ratio ranging from 3:1 to 6:1. Projection data for 6 and 3 mm PET scanner resolution were generated using analytic simulations and reconstructed without and with motion correction. Motion correction was achieved using motion compensated image reconstruction. The detectability performance was quantified by a receiver operating characteristic (ROC) analysis obtained using a channelized Hotelling observer and the area under the ROC curve (AUC) was calculated as the figure of merit. The results indicate that respiratory motion limits the detectability of lung and liver lesions, depending on the variation of the breathing cycle length and amplitude. Patients with large quiescent periods had a greater AUC than patients with regular breathing cycles and patients with long-term variability in respiratory cycle or higher motion amplitude. In addition, small (less than 10 mm diameter) or low contrast (3:1) lesions showed the greatest improvement in AUC as a result of applying motion correction. In particular, after applying motion correction the AUC is improved by up to 42% with current PET resolution (i.e. 6 mm) and up to 51% for higher PET resolution (i.e. 3 mm). Finally, the benefit of increasing the scanner resolution is small unless motion correction is applied. This investigation indicates high impact of respiratory motion correction on lesion detectability in PET and highlights the importance of motion correction in order to benefit from the increased resolution of future PET scanners

Pathogen-induced hatching and population-specific life-history response to water-borne cues in brown trout (Salmo trutta)

Hatching is an important niche shift, and embryos in a wide range of taxa can either accelerate or delay this life-history switch in order to avoid stage-specific risks. Such behavior can occur in response to stress itself and to chemical cues that allow anticipation of stress. We studied the genetic organization of this phenotypic plasticity and tested whether there are differences among populations and across environments in order to learn more about the evolutionary potential of stress-induced hatching. As a study species, we chose the brown trout (Salmo trutta; Salmonidae). Gametes were collected from five natural populations (within one river network) and used for full-factorial in vitro fertilizations. The resulting embryos were either directly infected with Pseudomonas fluorescens or were exposed to waterborne cues from P. fluorescens-infected conspecifics. We found that direct inoculation with P. fluorescens increased embryonic mortality and induced hatching in all host populations. Exposure to waterborne cues revealed population-specific responses. We found significant additive genetic variation for hatching time, and genetic variation in trait plasticity. In conclusion, hatching is induced in response to infection and can be affected by waterborne cues of infection, but populations and families differ in their reaction to the latter

Tolerance of whitefish embryos to Pseudomonas fluorescens linked to genetic and maternal effects, and reduced by previous exposure.

Juvenile or adult fish can alter their behaviour and rely on an innate and adaptive immune system to avoid/counteract pathogens, while fish embryos have to depend on egg characteristics and may be partly protected by their developing immune system that is building up from a certain age on. We developed an infection protocol that allows testing the reaction of individual whitefish embryos (Coregonus palaea) to repeated exposures to Pseudomonas fluorescens, an opportunistic bacterial fish pathogen. We used a full-factorial in vitro breeding design to separately test the effects of paternal and maternal contributions to the embryos' susceptibility to different kinds of pathogen exposure. We found that a first non-lethal exposure had immunosuppressive effects: pre-exposed embryos were more susceptible to future challenges with the same pathogen. At intermediate and high levels of pathogen intensity, maternal effects turned out to be crucial for the embryos' tolerance to infection. Paternal (i.e. genetic) effects played a significant role at the strongest level of infection, i.e. the embryos' own genetics already explained some of the variation in embryo susceptibility. Our findings suggest that whitefish embryos are largely protected by maternally transmitted substances, but build up some own innate immunocompetence several days before hatching

The weaker points of fish acute toxicity tests and how tests on embryos can solve some issues.

Fish acute toxicity tests play an important role in environmental risk assessment and hazard classification because they allow for first estimates of the relative toxicity of various chemicals in various species. However, such tests need to be carefully interpreted. Here we shortly summarize the main issues which are linked to the genetics and the condition of the test animals, the standardized test situations, the uncertainty about whether a given test species can be seen as representative to a given fish fauna, the often missing knowledge about possible interaction effects, especially with micropathogens, and statistical problems like small sample sizes and, in some cases, pseudoreplication. We suggest that multi-factorial embryo tests on ecologically relevant species solve many of these issues, and we shortly explain how such tests could be done to avoid the weaker points of fish acute toxicity tests