In the brain, a reduction in extracellular osmolality causes water-influx and swelling, which subsequently triggers Cl − - and osmolytes-efflux via volume-regulated anion channel (VRAC). Although LRRC8 family has been recently proposed as the pore-forming VRAC which is activated by low cytoplasmic ionic strength but not by swelling, the molecular identity of the pore-forming swelling-dependent VRAC (VRAC swell ) remains unclear. Here we identify and characterize Tweety-homologs (TTYH1, TTYH2, TTYH3) as the major VRAC swell in astrocytes. Gene-silencing of all Ttyh1/2/3 eliminated hypo-osmotic-solution-induced Cl − conductance (I Cl,swell ) in cultured and hippocampal astrocytes. When heterologously expressed in HEK293T or CHO-K1 cells, each TTYH isoform showed a significant I Cl,swell with similar aquaporin-4 dependency, pharmacological properties and glutamate permeability as I Cl,swell observed in native astrocytes. Mutagenesis-based structure-activity analysis revealed that positively charged arginine residue at 165 in TTYH1 and 164 in TTYH2 is critical for the formation of the channel-pore. Our results demonstrate that TTYH family confers the bona fide VRAC swell in the brain.

Purpose: To determine whether listening to music during cystoscopy decreases anxiety, pain, and dissatisfaction among patients and results in a more comfortable and better-tolerated procedure. Materials and Methods: Seventy male patients who underwent rigid cystoscopy between May 2011 and December 2011 were randomized into the following: no music (Group I, n = 35) or classical music during procedure (Group II, n = 35). Before cystoscopy, lidocaine gel was instilled in the urethra, and both groups viewed their procedures on a video monitor. Anxiety levels were quantified according to the State-Trait Anxiety Inventory. A visual analog scale (0-10) was used for a self-assessment of satisfaction, discomfort, and willingness among patients to repeat the cystoscopy. Results: Demographic characteristics, mean age, procedure duration, and procedure indications were statistically similar between the two groups. The mean anxiety level and mean pain score of Group II were significantly lower than those of Group I ( p < 0.001 for both). Group II also carried a significant greater mean satisfaction score compared with Group I ( p < 0.001). Statistically significant differences were detected between groups in the postprocedural pulse rate and the systolic blood pressure ( p = 0.012 and p = 0.008, respectively), whereas preprocedure pulse rate and systolic blood pressure were similar. Conclusions: Listening to music during rigid cystoscopy significantly reduces feelings of pain, discomfort, and dissatisfaction. Music can serve as a simple, inexpensive, and effective adjunct to sedation during cystoscopy. We recommend the application of music during rigid cystoscopy for clinical use.

Introduction Long-acting injectable testosterone undecanoate (TU, Nebido®), a new parenteral testosterone preparation, has recently been introduced to avoid frequent injections of the conventional injectable esters. Aims To assess the efficacy and safety of long-acting injectable testosterone undecanoate (TU, Nebido®) in Korean patients with testosterone deficiency syndrome (TDS). Methods One hundred thirty-three patients who complain of erectile dysfunction with serum testosterone level less than 3.5 ng/mL were injected with 1,000 mg of TU (4 mL/ample) on day 1, followed by another injection after 6 weeks and 18 weeks. For the safety profiles, serum hemoglobin (Hb), hematocrit (Hct), glucose, lipid profile, and prostate-specific antigen (PSA) were measured. Main Outcome Measures Body mass index (BMI) was measured at the time of the first visit and after 12, 24 weeks. Primary efficacy was evaluated according to changes in the International Index of Erectile Function (IIEF) from the initial visit to the final visit (24 weeks) and from the initial visit to each visit. Secondary efficacy was assessed with changes of the Aging Males’ Symptoms (AMS) Scale and the Global Efficacy Question (GEQ) for improvement of erectile function. Results Mean age of patients was 54 ± 9.6 years. Compared with pretreatment, no significant improvement in BMI was observed. Serum total testosterone and free testosterone were significantly increased at 12 weeks and were maintained until 24 weeks (P &lt;0.001). TU significantly decreased cholesterol (P &lt;0.0001). TU significantly improved total IIEF, all five domain scores of IIEF (P &lt;0.0001) and total AMS, all three domain scores of AMS (P &lt;0.0001). On GEQ, TU improved erectile function in 76.9% of subjects. On safety profile, TU significantly elevated Hb, Hct, and PSA at 24 weeks but within normal range. No serious adverse reactions were observed. Drop-out rate was 15.0%. Conclusions In this prospective multicenter study, TU was effective, safe, and tolerable until 24 weeks in Korean TDS patients. Further well-controlled, long-term study should follow.

We assessed the role of therapeutic delay time (TDT) in acute renal cortical scintigraphic lesion (ASL) and ultimate scar formation (USF) in children with first febrile UTI and whether it is affected by the presence of vesico-ureteral reflux (VUR). 230 children, 90 girls and 140 boys with first febrile UTI were included. Radiologic (USG, DMSA, and VCUG), clinical (age, gender, peak fever, therapeutic delay time) and laboratory (CBC with differential count, ANC (absolute neutrophil count), BUN, Creatinine, urine analysis, gram stain, culture, CRP and ESR) variables were analysed. DMSA was performed within 5 days and after six months. VCUG was performed after acute phase of UTI. The differences in TDT according to the presence of ASL, USF and VUR were assessed. And the correlation between ASL or USF with the duration of TDT was assessed. Of 230 patients enrolled, 142 patients had refluxing UTI and 88 patients had non-refluxing UTI. TDT was the risk factor associated with ASL and USF along with presence of VUR. TDT was longer in ASL positive group compared with the ASL negative group. Also USF group showed longer TDT compared with those without USF in both refluxing UTI and non refluxing UTI. The TDT was significantly shorter in USF group with the presence of VUR. Positive linear association was noted between prevalence of ASL and USF and duration of TDT. In conclusion, the impact of UTI on formation of USF may be enhanced by the presence of VUR with shorter duration of TDT.

The neuronal activity-dependent change in the manner in which light is absorbed or scattered in brain tissue is called the intrinsic optical signal (IOS), and provides label-free, minimally invasive, and high spatial (~100 µm) resolution imaging for visualizing neuronal activity patterns. IOS imaging in isolated brain slices measured at an infrared wavelength (>700 nm) has recently been attributed to the changes in light scattering and transmittance due to aquaporin-4 (AQP4)-dependent astrocytic swelling. The complexity of functional interactions between neurons and astrocytes, however, has prevented the elucidation of the series of molecular mechanisms leading to the generation of IOS. Here, we pharmacologically dissected the IOS in the acutely prepared brain slices of the stratum radiatum of the hippocampus, induced by 1 s/20 Hz electrical stimulation of Schaffer-collateral pathway with simultaneous measurement of the activity of the neuronal population by field potential recordings. We found that 55% of IOSs peak upon stimulation and originate from postsynaptic AMPA and NMDA receptors. The remaining originated from presynaptic action potentials and vesicle fusion. Mechanistically, the elevated extracellular glutamate and K + during synaptic transmission were taken up by astrocytes via a glutamate transporter and quinine-sensitive K2P channel, followed by an influx of water via AQP-4. We also found that the decay of IOS is mediated by the DCPIB- and NPPB-sensitive anion channels in astrocytes. Altogether, our results demonstrate that the functional coupling between synaptic activity and astrocytic transient volume change during excitatory synaptic transmission is the major source of IOS.

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The clinical usefulness of vitamin D for treatment of hypogonadism or LUTS/BPH varies according to metabolic status.

Purpose: The aim of this study was to compare cure rates and complications of polydimethylsiloxane (Macroplastique Ⓡ ) and dextranomer/hyaluronic acid copolymer (Deflux Ⓡ ) in the treatment of vesicoureteral reflux (VUR). Materials and Methods: From April 2001 to March 2008, 29 boys and 42 girls (total of 115 ureters) with a mean age of 6 years who had undergone endoscopic subureteral transurethral injection for VUR were enrolled. A single subureteral injection of Macroplastique was performed in 31 ureters in 23 children (group I; grade II: 4; grade III: 12; grade IV: 9; grade V: 6), and a single subureteral injection of Deflux was performed in 84 ureters in 48 children (group II; grade II: 24; grade III: 14; grade IV: 25; grade V: 21). Renal ultrasound was done 1 day after injection, and voiding cystourethrography (VCUG) was done at 3 months. Successful reflux correction was defined as absent or grade I reflux on follow-up VCUG. Results: No significant difference in success rates was observed between group I and group II [80.6% (25/31) vs. 78.6% (66/84), respectively, p＞0.05]. The following postoperative complications developed: ureteral obstruction in 2 ureters of group I and 3 ureters of group II, asymptomatic urinary tract infection in 3 patients of group I and 2 patients of group II, and bladder calcification by erosion or mucosal necrosis in 2 patients of group I. Conclusions: Despite differences in material properties, both Macroplastique and Deflux were safe for the treatment of children with VUR. Because of the risk of bladder mucosal necrosis and substantial decreases in volume after implantation, long-term follow-up is required.