Presynaptic nerve terminals must maintain stable neurotransmissions via synaptic vesicle (SV) resupply despite encountering wide fluctuations in the number and frequency of incoming action potentials (APs). However, the molecular mechanism linking variation in neural activity to SV resupply is unknown. Myosins II and VI are actin-based cytoskeletal motors that drive dendritic actin dynamics and membrane transport, respectively, at brain synapses. Here we combined genetic knockdown or molecular dysfunction and direct physiological measurement of fast synaptic transmission from paired rat superior cervical ganglion neurons in culture to show that myosins IIB and VI work individually in SV reuse pathways, having distinct dependency and time constants with physiological AP frequency. Myosin VI resupplied the readily releasable pool (RRP) with slow kinetics independently of firing rates but acted quickly within 50 ms after AP. Under high-frequency AP firing, myosin IIB resupplied the RRP with fast kinetics in a slower time window of 200 ms. Knockdown of both myosin and dynamin isoforms by mixed siRNA microinjection revealed that myosin IIB-mediated SV resupply follows amphiphysin/dynamin-1-mediated endocytosis, while myosin VI-mediated SV resupply follows dynamin-3-mediated endocytosis. Collectively, our findings show how distinct myosin isoforms work as vesicle motors in appropriate SV reuse pathways associated with specific firing patterns.

Selective identification of men with clinically significant prostate cancer (sPC) is a pivotal issue. Development of a risk model for detecting sPC based on the prostate imaging reporting and data system (PI-RADS) for bi-parametric magnetic resonance imaging (bpMRI) and clinical parameters in a Japanese cohort is expected to prove beneficial. We retrospectively analyzed clinical parameters and bpMRI findings from 773 biopsy-naïve patients between January 2011 and December 2016. A risk model was established using multivariate logistic regression analysis and presented on a nomogram. Discrimination of the risk model was compared using the area under the receiver operating characteristic curve. Statistical differences between the predictive model and clinical parameters were analyzed using DeLong test. sPC was detected in 343 men (44.3%). Multivariate logistic regression analysis to predict sPC revealed age (P = 0.002), log prostate-specific antigen (P < 0.001), prostate volume (P < 0.001) and PI-RADS scores (P < 0.001) as significant contributors to the model. Area under the curve was higher for the risk model (0.862), than for age (0.646), log prostate-specific antigen (0.652), prostate volume (0.697) or imaging score (0.822). DeLong test results also showed that the novel risk model performed significantly better than those parameters (P < 0.05). This novel risk model performed significantly better compared with PI-RADS scores and other parameters alone, and is thus expected to prove beneficial in making decisions regarding biopsy on suspicion of sPC.

Introduction The effectiveness of nivolumab plus ipilimumab for metastatic renal cell carcinoma with inferior vena cava tumor thrombus remains unclear. Case presentation A 75‐year‐old male was diagnosed with metastatic renal cell carcinoma with inferior vena cava tumor thrombus and treated with nivolumab plus ipilimumab. The renal mass and thrombus regressed and all pulmonary nodules except for one lesion diminished. To avoid thrombotic complications, radical nephrectomy and thrombectomy were performed. No viable malignant cells were revealed histopathologically. Although nivolumab was continued after the surgical interventions, the remaining lesion did not change. Considering the discontinuation of nivolumab, metastasectomy was performed, and no viable malignant cells were revealed histopathologically. There has been no recurrence after the discontinuation. Conclusion Nivolumab plus ipilimumab could have effectiveness for metastatic renal cell carcinoma with inferior vena cava tumor thrombus.

Introduction To clarify the mechanisms responsible for running‐induced asymptomatic gross hematuria. Case presentation We identified 12 patients who visited our outpatient clinic with hematuria after running as a chief complaint. In 9 of 12 patients (75%), cystoscopic findings revealed mucosal contusions at the center of the posterior wall. Our examination including cystoscopy and magnetic resonance imaging revealed that this bladder contusion development was caused by the repeated contact of the bladder posterior wall against the fixed bladder neck by vertical motion in the empty bladder lumen during running. All patients with bladder contusion were male because the bladder neck is more firmly fixed to the pelvic floor by the protruding prostate in men than women. Gross hematuria in all patients quickly resolved without treatment after running cessation. Conclusion This is the first report in which cystoscopic findings showed that running‐induced macroscopic hematuria can be frequently caused by traumatic bladder contusion.

Objective: The aim of this study was to investigate the efficacy and safety of tadalafil add-on therapy with α 1 -adrenoceptor antagonists.Methods: Patients with persistent storage symptoms refractory to α 1 -adrenoceptor antagonists for benign prostatic hyperplasia were enrolled in the study. Patients were randomly assigned to either a 5 mg tadalafil or 5 mg solifenacin treatment group for 12 weeks. International Prostate Symptom Score, Overactive Bladder Symptom Score, urinary flow rates, residual urine volume, and blood pressure were measured prospectively before treatment and after 4 and 12 weeks of treatment. Changes from baseline were compared between groups. The rate of treatment discontinuation due to adverse effects was evaluated.Results: Of the 75 patients recruited to the study, 38 and 37 were assigned to the tadalafil and solifenacin groups, respectively. There were no significant difference in baseline characteristics between the two groups. The change in the amount of residual urine volume was significantly larger in the solifenacin-than tadalafil-treated group; other parameters, including lower urinary tract symptoms and uroflowmetry measures, did not differ significantly between the two groups. Seven (18%) and 12 (32%) patients in the tadalafil and solifenacin groups, respectively, discontinued treatment because of adverse events. The main reasons for discontinuation in the tadalafil group were stomach discomfort or nausea and dizziness or vertigo; voiding difficulty and constipation were the main reasons for discontinuation in the solifenacin group. There was no significant difference in blood pressure fluctuations from baseline between the two groups.Conclusions: Tadalafil add-on therapy was not inferior to solifenacin add-on therapy in terms of effect and safety. Therefore, tadalafil could be an alternative add-on drug for patients with persistent lower urinary tract symptoms refractory to α 1 -adrenoceptor antagonists. K E Y W O R D S α 1 -adrenoceptor antagonist, benign prostatic hyperplasia, lower urinary tract symptoms, overactive bladder, solifenacin succinate, tadalafil 1 | INTRODUCTION Benign prostatic hyperplasia (BPH) is a representative underlying disease that triggers lower urinary tract symptoms (LUTS). Aging-related prostate enlargement triggers mechanical prostatic urethral obstruction, increases the density of α 1 -adrenoceptors in the bladder neck and prostatic urethra, and decreases nitric oxide (NO) secretion. 1 These result in smooth muscle hypertonia of the lower urinary tract, causing functional obstruction. In addition, most cases of BPH involve LUTS, such as voiding difficulties and storage symptoms due to an