The influence of learning history on anterograde interference.

Classically interpreted as a competition between opposite memories (A vs B), anterograde interference (AI) also emerges in the absence of competing memories (A vs A), suggesting that mechanisms other than those involved in memory competition contribute to AI. To investigate this, we tested the hypothesis that extending motor practice would enhance a first memory, but come at the cost of reduced learning capabilities when subsequently exposed to a second learning session of the same task. Based on converging biological evidence, AI was expected to depend upon the degree of extended practice of the initial exposure. During a first Session, four conditions were carried out where participants (n = 24) adapted to a gradually introduced -20° visual deviation while the extent of the initial exposure was manipulated by varying the duration or type of the performance asymptote. Specifically, the performance asymptote at -20° was either Short (40 trials), Moderate (160 trials), Long (320 trials), or absent due to continuously changing perturbations around the mean of -20° (Jagged; 160 trials). After a 2-min interval, participants re-adapted to the same (-20°) visual deviation, which was meant to probe the effect of extended practice in the first Session on the learning capabilities of a second identical memory (A vs A). The results first confirmed that the duration of exposure in the first Session enhanced immediate aftereffects in the Moderate, Long, and Jagged conditions as compared to the Short condition, suggesting that extended practice enhanced retention of the first memory. When comparing the second Session to the first one, results revealed a different pattern of re-adaptation depending on the duration of initial exposure: in the Short condition, there was evidence for facilitated re-adaptation and similar aftereffects. However, in the Moderate, Long and Jagged conditions, re-adaptation was similar and aftereffects were impaired, suggestive of AI. This suggests that extended practice initially enhances memory formation, but comes at the cost of reduced subsequent learning capabilities. One possibility is that AI occurs because extended practice induces the emergence of network-specific homeostatic constraints, which limit subsequent neuroplastic and learning capabilities in the same neural network.

Punishments and rewards both modestly impair visuomotor memory retention.

While the effects of rewards on memory appear well documented, the effects of punishments remain uncertain. Based on neuroimaging data, this study tested the hypothesis that, as compared to a neutral condition, a context allowing successful punishment avoidance would enhance memory to a similar extent as rewards. In a fully within-subject and counter-balanced design, participants (n = 18) took part in 3 distinct learning sessions during which the delivery of performance-contingent monetary punishments and rewards was manipulated. Specifically, participants had to reach towards visual targets while compensating for a gradually introduced visual deviation. Accuracy at achieving targets was either punished (Hit: "+0$"; Miss: "-0.5$), rewarded (Hit: "+0.5$"; Miss: "-0$"), or associated with neutral binary feedback (Hit: "Hit"; Miss: "Miss"). Retention was assessed through reach aftereffects both immediately and 24 h after initial acquisition. The results disconfirmed the hypothesis by showing that the punishment and reward learning sessions both impaired retention as compared to the neutral session, suggesting that both types of incentives similarly impaired memory formation and consolidation. Two alternative but complementary interpretations are discussed. One interpretation is that the presence of punishments and rewards induced a negative learning context, which - based on neurobiological data - could have been sufficient to interfere with memory formation and consolidation. Another interpretation is that punishments and rewards emphasized the disrupting effects of target hits on implicit learning processes, therefore yielding retention impairments. Altogether, these results suggest that incentives can have counter-productive effects on memory.

Learning the same motor task twice impairs its retention in a time- and dose-dependent manner.

Anterograde interference emerges when two differing tasks are learned in close temporal proximity, an effect repeatedly attributed to a competition between differing task memories. However, recent development alternatively suggests that initial learning may trigger a refractory period that occludes neuroplasticity and impairs subsequent learning, consequently mediating interference independently of memory competition. Accordingly, this study tested the hypothesis that interference can emerge when the same motor task is being learned twice, that is when competition between memories is prevented. In a first experiment, the inter-session interval (ISI) between two identical motor learning sessions was manipulated to be 2 min, 1 h or 24 h. Results revealed that retention of the second session was impaired as compared to the first one when the ISI was 2 min but not when it was 1 h or 24 h, indicating a time-dependent process. Results from a second experiment replicated those of the first one and revealed that adding a third motor learning session with a 2 min ISI further impaired retention, indicating a dose-dependent process. Results from a third experiment revealed that the retention impairments did not take place when a learning session was preceded by simple rehearsal of the motor task without concurrent learning, thus ruling out fatigue and confirming that retention is impaired specifically when preceded by a learning session. Altogether, the present results suggest that competing memories is not the sole mechanism mediating anterograde interference and introduce the possibility that a time- and dose-dependent refractory period-independent of fatigue-also contributes to its emergence. One possibility is that learning transiently perturbs the homeostasis of learning-related neuronal substrates. Introducing additional learning when homeostasis is still perturbed may not only impair performance improvements, but also memory formation.

Administration of neoadjuvant chemotherapy for muscle-invasive bladder cancer in real life: Are urologists still too cautious?

INTRODUCTION: Neoadjuvant chemotherapy (NAC) is now recommended to treat muscle-invasive bladder cancer (MIBC) but is not always executed in real life. This study aims to evaluate the proportion of patients with MIBC who receive an optimal NAC, and to present the predictive factors of its achievement. METHODS: This monocenter retrospective study included all the patients who underwent radical cystectomy for≥pT2NxM0 MIBC between 2013, January and 2018, December. NAC consisted in 4-6 cycles of MVAC (methotrexate, vinblastine, adriamycin, and cisplatin) or 4 cycles of GC (gemcitabin, and carboplatin). Demographic (sex, age, ECOG-PS, glomerular filtration rate [GFR], and cN stage), surgical (urinary derivation, time of surgery, blood loss, and complications), and oncological characteristics were analyzed. Multivariate analysis are made to find predictors of administration of NAC. RESULTS: One hundred and twenty-seven patients were included. Thirty received CNA (24%). Patients who underwent CNA were younger, with better ECOG and better GFR. Multivariate analysis showed that cN+ stage and better GFR were significantly associated to administration of NAC. Eight patients (27%) couldn't receive an optimal treatment due to toxicity. Perioperative complication rates were similar, with or without NAC. Patients who underwent NAC had a worse GFR after treatment (-17 versus +5mL/min, P<0.01). CONCLUSION: Due to the risks of toxicity, NAC can only be proposed to selected population, which is not the current patients. Immunotherapy could allow to treat more patients because of better tolerance. LEVEL OF EVIDENCE: 3.

Sexual dysfunction after elective laparoscopic or endovascular abdominal aortic aneurysm repair in men.

INTRODUCTION: Infrarenal abdominal aortic aneurysm (AAA) repair can lead to ejaculation and erection troubles in men. There are few studies on sexual dysfunction after endovascular repair (EVAR) but they suggest less retrograde ejaculation than after open repair. We assessed the sexual dysfunction and ejaculation troubles after elective laparoscopic repair or EVAR. METHODS: We conducted a monocentric prospective study on 124 patients undergoing AAA repair between 2013 and 2015. Sexual function was evaluated using the IIEF-15 questionnaire and questions on ejaculation. RESULTS: Only 45 patients (36.3%) accepted to complete the IIEF preoperatively with 20-37.8% having preoperative sexual dysfunction. Among them, 21 (46.7%) accepted to complete the questionnaire at 3, 6 and 12 months. Mean age at inclusion was 65±5.6 years in the laparoscopic group and 77±10.5 years in the EVAR group (P=0.003). Erectile and sexual function were slightly improved at 12 months in the laparoscopic group (+1.4 for erectile score and +4.6 for IIEF score) with no significant difference (P=0.83 and 0.74) whereas 8 patients (61.5%) had persistent ejaculation troubles at 3 months. In the EVAR group, patients had moderate sexual dysfunction at baseline without improvement at 12 months, but only one patient reported ejaculation troubles. CONCLUSIONS: Most patients eligible for AAA repair present with baseline erectile and sexual dysfunction. Laparoscopic AAA repair provides no onset of erectile or sexual dysfunction but a global improvement after surgery. Ejaculation troubles are frequent and persistent at 1 year. However, EVAR treatment, doesn't allow recovering of sexual function at 1 year. LEVEL OF EVIDENCE: 4.

Secondary bladder exstrophy repair with a bilateral gracilis muscle flap in an adult female patient: Case report of an original procedure.

Classical bladder exstrophy (CBE), affecting 1 birth out of 30,000, is characterized by an evaginated bladder plate through a defect in the lower abdominal wall, multiple abdominal wall anomalies including a pubic bone arch dehiscence. Numerous approaches from childhood to adulthood are thus required, depending on the severity of the deformity, including the associated genital anomalies. We report the case of a 19-year-old woman with CBE with a history of three-failed primary closure. We performed a secondary neck closure with a concomitant suspension of the bladder neck and reconstruction of the lower abdominal wall using a bilateral gracilis muscle flap transposition. The early postoperative course was uneventful. The patient was discharged at day ten postoperatively. The upper part of the genital sutures (labia minora) secondary healed in three weeks. Assessment at 2, 6 and 16 months postoperatively, respectively noticed a complete healing with successful sexual intercourses, perceived gracilis contraction by the patient, and finally, recent attempts to get pregnant. Neither urinary infection nor urinary leaks occurred. Bilateral crossed gracilis muscles transfer linking both rectus abdominis muscle in front of the reconstructed bladder neck might benefit to bladder exstrophy patients.

[Comparison of operative and oncologic results between partial nephrectomy and radiofrequency ablation for treatment of renal tumors in patients older than 75]. / Comparaison des résultats opératoires et oncologiques de la néphrectomie partielle et de l'ablation par radiofréquence pour traitement des tumeurs rénales chez les patients de plus de 75 ans.

INTRODUCTION: Elderly patients represent a growing part of our society for who treatment strategy for localized renal tumors has to be chosen knowing iatrogen effects and renal function morbidity. The aim was to analyze oncological and functional results of nephron sparing surgery (PN) versus radiofrequency ablation (RFA). MATERIALS AND METHODS: All patients aged more than 75 treated by partial nephrectomy or radiofrequency ablation between 2007 and 2014 in our centre were included. Patient and tumors data were compared and these criteria were analyzed: survival (overall and without recurrence) and loss of renal function (pre- and postoperative MDRD). RESULTS: In total, 100 patients were included (26 partial nephrectomies, group 1 and 74 radiofrequency ablation, group 2) with a 32-months medium follow-up. Medium age and tumor size were significantly different (respectively, 78 versus 81 years old, P=0.001, 38mm versus 29mm, P=0.003). Perioperative results showed no differences in complications. Transfusion rate and duration of hospital stay were significantly higher in the PN group. Median overall survival were 45 vs. 27 months (P=0.23) for PN and RFA and median recurrence-free survival were 28 vs. 10 months (P=0.34). On a multivariate analysis, operative technique (PN or RFA) were not significantly linked to survival (HR 2.37 [95% CI: 0.66-8.5]), P=0.19. Loss of renal function were 1.5±14mL/min/1.73m2 for PN and 3±14mL/min/1.73m2 for RFA (P=0.69). CONCLUSION: Our study showed better perioperative results for RFA than for PN, without significant different survival. Loss of renal function were little and similar. LEVEL OF EVIDENCE: 4.

Imeglimin prevents human endothelial cell death by inhibiting mitochondrial permeability transition without inhibiting mitochondrial respiration.

Imeglimin is the first in a new class of oral glucose-lowering agents, having recently completed its phase 2b trial. As Imeglimin did show a full prevention of ß-cell apoptosis, and since angiopathy represents a major complication of diabetes, we studied Imeglimin protective effects on hyperglycemia-induced death of human endothelial cells (HMEC-1). These cells were incubated in several oxidative stress environments (exposure to high glucose and oxidizing agent tert-butylhydroperoxide) which led to mitochondrial permeability transition pore (PTP) opening, cytochrome c release and cell death. These events were fully prevented by Imeglimin treatment. This protective effect on cell death occurred without any effect on oxygen consumption rate, on lactate production and on cytosolic redox or phosphate potentials. Imeglimin also dramatically decreased reactive oxygen species production, inhibiting specifically reverse electron transfer through complex I. We conclude that Imeglimin prevents hyperglycemia-induced cell death in HMEC-1 through inhibition of PTP opening without inhibiting mitochondrial respiration nor affecting cellular energy status. Considering the high prevalence of macrovascular and microvascular complications in type 2 diabetic subjects, these results together suggest a potential benefit of Imeglimin in diabetic angiopathy.

[Cancer genetic screening for patient with multiple renal tumors: What is the current practice for what results?]. / Dépistage oncogénétique des patients atteints de tumeurs rénales multiples : quelle pratique pour quels résultats ?

AIM: To evaluate in a high volume center the practice and the performance of cancer genetic screening for patients with multiple renal tumors without a predisposition to kidney tumors known at the time of surgery. METHOD: All patients treated for multiple renal tumors from January 2000 to December 2013 in our center were included. Patients with a family history of renal cell carcinoma, a kidney disease or a genetic predisposition to renal cancer known at the time of surgery were excluded from the analysis. Our list of patients was retrospectively compared to the records from PREDIR (PREDisposition to Kidney Tumors) center of Île-de-France, which regionally centralizes the care of patients with kidney tumors associated with a genetic predisposition. RESULTS: One hundred and thirty-six patients were included. Twenty-six patients of 136 (19%) were referred to PREDIR center: 23 followed the screening and 3 did not show up in consultation. Of the 23 patients screened, three genetic predispositions to kidney tumors were identified (13%). Of the 95 patients with synchronous tumors, 48% with more than 3 tumors benefited from cancer genetics investigation against 13% of those presenting only two tumors. CONCLUSION: Our study shows that cancer genetic investigations are not routinely offered to patients with multiple kidney tumors, conversely to existing guidelines. Urologists must be aware of this screening. LEVEL OF EVIDENCE: 4.

[Conservative management of upper tract urinary fistulae using ureteral trans-vesico-parietal stent]. / Traitement conservateur des fistules urinaires du haut appareil par sonde urétérale trans-vésico-pariétale.

OBJECTIVES: Ureteral stents and ureteral catheters externalized through the urethra are not ideal solutions to manage complicated upper urinary tract fistulae. We sought an effective method of drainage, minimally invasive, reproducible allowing a rapid patient's discharge. PATIENTS AND METHODS: Between November 2013 and February 2015, an ureteral stent was exteriorized in trans-vesico-parietal by an endoscopic and percutaneous access in patients with complicated upper urinary tract fistulae. Monitoring of tolerance, complications and urinary fistula healing was performed. RESULTS: Nine consecutive patients had an ureteral stent exteriorized in trans-vesico-parietal to manage complicated upper urinary tract fistulae. There was no failure in introducing the catheter, or postoperative complication. Catheters were left in place on average 36.1days (24-55). The patients were able to return home with the catheter in place in 77.8% of cases. The tolerance of the catheter was good. All fistulae were able to be treated conservatively at the end of the drainage period. CONCLUSION: Trans-vesico-parietal ureteral catheters enable efficient and reproducible conservative treatment of upper tract urinary fistulae regardless of their cause. LEVEL OF EVIDENCE: 5.

A retrospective study of canine prostatic diseases from 2002 to 2009 at the Alfort Veterinary College in France.

A retrospective study was used to investigate the incidence of prostatic diseases in a large population of dogs at Alfort Veterinary Hospital and to clarify epidemiologic features, which might be of a great help to veterinarians in managing and discriminating prostatic disorders. During the investigation period, a total of 72,300 male dogs (coming mainly from the Ile-de-France region) were registered in the Alfort Veterinary College database, and 481 of them (0.7%) were found to have prostatic disorder. The diagnosis was carried out on the basis of clinical signs and ultrasound findings. Among dogs experiencing a prostatic disorder, most frequently recorded diseases were benign prostatic hyperplasia (45.9%) and prostatitis (38.5%), followed by abscesses (7.7%), cysts (5.0%), neoplasia (2.6%), and squamous metaplasia (0.2%). Our study revealed an incidence of 0.3% of prostatic disorders observed in intact male dogs, except in the case of prostatic neoplasia. The mean age of the dogs experiencing prostatic disorders was 8.6 ± 3.2 years. This was significantly different (P < 0.001). Large dogs were significantly more affected by prostatic disorders (P < 0.05), except for prostatic neoplasia. A breed predisposition was suspected in German Shepherd (odds ratio [OR] = 2.1; 95% confidence interval [CI]: 1.5-2.9), Rottweiler (OR = 1.8; 95% CI: 1.2-2.7), American Staffordshire Terrier (OR = 3.8; 95% CI: 2.5-5.8), Berger de Beauce (OR = 3.7; 95% CI: 2.2-6.1), and Bernese Mountain Dog (OR = 2.5; 95% CI: 1.3-4.7).