HER2 Amplification in p53-Mutated Endometrial Carcinomas.

p53-mutated endometrial carcinomas tend to recur and develop distant metastases. Therefore, the detection of new potential therapeutic targets such as HER2 is particularly interesting. In this retrospective study, which considered over 118 endometrial carcinomas, the p53 mutation was detected in 29.6% of cases. In these cases, the HER2 protein profile was studied via immunohistochemistry, and an overexpression of HER2 protein (++ or +++) was noted in 31.4%. The CISH technique was used in these cases to determine if gene amplification was present. In 18% of cases, the technique was not conclusive. Amplification of the HER2 gene was observed in 36.3% of cases and 36.3% of cases showed a polysomal-like aneusomy for centromere 17. Amplification was found in serous carcinomas, clear cell carcinomas and carcinosarcomas, highlighting the future potentiality of HER2-targeted therapies in these variants of aggressive carcinomas.

Heart Rate Variability During a Standard Dive: A Role for Inspired Oxygen Pressure?

Introduction: Heart rate variability (HRV) during underwater diving has been infrequently investigated because of environment limitations and technical challenges. This study aims to analyze HRV changes while diving at variable hyperoxia when using open circuit (OC) air diving apparatus or at constant hyperoxia using a closed-circuit rebreather (CCR). We used HRV analysis in time and frequency domain adding nonlinear analysis which is more adapted to short-time analysis and less dependent on respiratory rate (Sinus respiratory arrhythmia). Materials and Methods: 18 males, 12 using OC (30 mfw for 20 min) and 6 using CCR (30 mfw for 40 min.). HRV was recorded using a polar recorder. Four samples of R-R intervals representing the dive were saved for HRV analysis. Standard deviation of normal-to-normal intervals (SDNN), square root of the mean squared differences between successive RR intervals (rMSSD), and average RR intervals (RR) in time-domain; low frequency (LF) and high frequency (HF) in frequency domain were investigated. Nonlinear analysis included fractal dimension (FrD). Results: SDNN and rMSSD were significantly increased during descent and at depth with OC, not with CCR. Mean RR interval was longer at depth with OC, but only during ascent and after the dive with CCR. HF power was higher than baseline during the descent both with OC and CCR and remained elevated at depth for OC. The LF/HF ratio was significantly lower than baseline for descent and at depth with both OC and CCR. After 30 min of recovery, the LF/HF ratio was higher than baseline with both OC and CCR. Nonlinear analysis detected differences at depth for OC and CCR. Discussion: Increased parasympathetic tone was present during diving. RR duration, SDNN; rMSSD, HF spectral power all increased during the dive above pre-dive levels. Conversely, HF power decreased (and the LF/HF increased) 30 min after the dive. Using FrD, a difference was detected between OC and CCR, which may be related to differences in partial pressure of oxygen breathed during the dive.

Critical Flicker Fusion Frequency: A Marker of Cerebral Arousal During Modified Gravitational Conditions Related to Parabolic Flights.

In situ evaluation of human brain performance and arousal remains challenging during operational circumstances, hence the need for a rapid, reliable and reproducible tool. Here we hypothesized that the Critical flicker fusion frequency (CFFF) reflecting/requiring visual integration, visuo-motor skills and decision-taking process might be a powerful, fast and simple tool in modified gravity environments. Therefore 11 male healthy volunteers were assessed for higher cognitive functions with CFFF during parabolic flights. They were assessed at different time points: upon arrival to the base, 30 min after subcutaneous scopolamine administration, before parabolas, during hypergravity and microgravity at break time (between the 16th and the 17th parabola), on the return flight and on the ground after landing. First, a stable, and consistent measurement of CFFF could be obtained within 12 s. Second, under modified gravitational conditions, the perceptual ability of participants is significantly modified. Compared to the baseline, evolution is characterized by a significant increase of CFFF when in microgravity (0g: 106.9 ± 5.5%), and a significant decrease of CFFF while in hypergravity (2g: 94.5 ± 3.8%). Other time-points were not statistically different from the baseline value. Although the underlying mechanism is still debated, we suggest that the CFFF test is a global marker of cerebral arousal as the result of visuo-motor and decision taking testing based on a simple visual stimulus with an uncomplicated set up that could be used under various environmental conditions. The authors express an opinion that it would be advisable to introduce CFFF measurement during spaceflights as it allows individual longitudinal assessment of individual ability even under conditions of incomplete physiological compensation, as shown here during parabolic flights.