Deteriorative changes in behavioral functions are natural processes that accompany aging. In advanced aged C. elegans nematodes, gross decline in general behaviors, such as locomotion and feeding, is correlated with degeneration of muscle structure and contractile function. In this study, we characterized the age-related changes in C. elegans male mating behavior to determine possible causes that ultimately lead to age-related muscle frailty. Unlike the kinetics of general behavioral decline, we found that mating behavior deteriorates early in adulthood, with no obvious muscle fiber disorganization or sperm dysfunction. Through direct mating behavior observations, Ca2+ imaging and pharmacological tests, we found that the muscular components used for mating become more excitable as the males age. Interestingly, manipulating either the expression of AChR genes or dietary-mediated ether-a-go-go family K+ channel function can reduce the muscle excitability of older males and concurrently improve mating behavior, suggesting a correlation between these biological processes.

Pentameric ligand-gated ion channels (pLGICs), also called Cys-loop receptors in eukaryotic superfamily members, play diverse roles in neurotransmission and serve as primary targets for many therapeutic drugs. Structural studies of full-length eukaryotic pLGICs have been challenging because of glycosylation, large size, pentameric assembly, and hydrophobicity. X-ray structures of prokaryotic pLGICs, including the Gloeobacter violaceus LGIC (GLIC) and the Erwinia chrysanthemi LGIC (ELIC), and truncated eukaryotic pLGICs have significantly improved and complemented the understanding of structural details previously obtained with acetylcholine-binding protein and Torpedo nicotinic acetylcholine receptors. Prokaryotic pLGICs share their overall structural features with eukaryotic pLGICs for the ligand-binding extracellular and channel-lining transmembrane domains. The large intracellular domain (ICD) is present only in eukaryotic members and is characterized by a low level of sequence conservation and significant variability in length (50–250 amino acids), making the ICD a potential target for the modulation of specific pLGIC subunits. None of the structures includes a complete ICD. Here, we created chimeras by adding the ICD of cation-conducting (nAChR-α7) and anion-conducting (GABAρ1, Glyα1) eukaryotic homopentamer-forming pLGICs to GLIC. GLIC–ICD chimeras assemble into pentamers to form proton-gated channels, as does the parent GLIC. Additionally, the sensitivity of the chimeras toward modulation of functional maturation by chaperone protein RIC-3 is preserved as in those of the parent eukaryotic channels. For a previously described GLIC–5HT3A–ICD chimera, we now provide evidence of its successful large-scale expression and purification to homogeneity. Overall, the chimeras provide valuable tools for functional and structural studies of eukaryotic pLGIC ICDs.

HoLEP can be performed safely and effectively post-PUL; however, device implants may be found in areas other than the intended location, and morcellation of the adenoma tissue is complicated by metallic implants of the PUL device.

Introduction: We sought to provide a technical update on the use of a prostate morcellator device (PMD) to manage organized blood clots of the bladder following laser prostatectomy. Methods: Herein, we describe our experience in using the Wolf Piranha morcellator in managing organized bladder blood clots supplemented with a retrospective chart review of the patients in whom this procedure was performed. Results: Six patients, all male with a mean age of 75 ± 8.9 years, had organized bladder clots following either holmium laser enucleation or photoselective vaporization of the prostate managed with a PMD. Clots were recognized based on hematuria or urinary retention a median of 3.5 days following the aforementioned procedures. Initial management was attempted with more conservative measures, including a three-way Foley catheter, followed by cystoscopy with an Ellik evacuator, or a glass Tommey syringe. Morcellation times were a mean of 10.2 ± 6.15 minutes (range 2-18). This technique was able to manage clots that were an average of 173.3 ± 115.9 cc in size. The procedure was well-tolerated. No patients experienced intraoperative or morcellator-related complications. Conclusions: Benign prostatic hypertrophy frequently requires surgical endoscopic management and can be complicated by hematuria and bladder blood clot formation. When these clots become organized, this can lead to urinary retention and the required management, evacuation, may be difficult. The use of a Wolf Piranha PMD is a safe, well-tolerated, and effective in evacuating organized blood clots of the bladder. IntroductionAlthough photoselective vaporization of the prostate (PVP) and holmium laser enucleation of the prostate (HoLEP) have been shown to have significantly less blood loss and are less likely to require transfusion than transurethral resection of the prostate (TURP) and open simple prostatectomy, these techniques are not without bleeding complications. [1][2][3][4][5][6][7] Blood clots within the bladder postoperatively can be removed by a number of methods, including hand irrigation through a Foley catheter or cystoscopic evacuation with an evacuation device. [8][9][10] Large, organized blood clots within the bladder causing urinary retention that are refractory to these classic management techniques pose a significant challenge to the surgeon.Herein, we demonstrates a novel method for evacuating organized bladder clots causing urinary retention using a prostate morcellation device (PMD) after laser prostate surdevice (PMD) after laser prostate surafter laser prostate surgery for benign prostatic hyperplasia (BPH). The safety and effectiveness of the use of a PMD to evacuate organized bladder blood clot is demonstrated. Methods PatientsFollowing institutional review board approval, six patients included in this series underwent bladder clot evacuation using a PMD between August 2015 and April 2016, five patients post-HoLEP and one post-PVP. The overall rate of clot retention following the aforementioned procedures was 1.74%. Equ...

The treatments explored in this experiment provided novel examples of cost-effective porcine models for the study of nephrolithiasis. EG + VD had the strongest indicators of nephrolithiasis without nephrotoxicity.

Introduction: Return for unplanned postoperative care is an important quality metric in the United States. Most of our postoperative return visits occur after ureteroscopy. Routine preoperative ureteral stenting is not recommended by the American Urological Association due to its impact on the quality of life, despite its proposed operative advantages. We evaluated the association between preoperative ureteral stenting and the resulting perioperative outcomes in the context of quality measures such as return to the emergency department (ED) and readmission rates. Materials and Methods: After the Institutional Review Board approval, a retrospective review of patients undergoing ureteroscopy from February 2014 to present was conducted. Patient's demographics and perioperative outcomes were compared based on the presence or absence of a ureteral stent before ureteroscopy. Details and rates of nurse calls, returns to the ED, and readmissions within 90 days were also compared. Results: A total of 421 instances of ureteroscopy, 278 prestented ureteroscopy (psURS), and 143 direct ureteroscopy (dURS) were included for analysis. Preoperative demographics were similar. The psURS cohort was more likely to undergo flexible ureteroscopy, utilized an access sheath more often ( P < 0.0001), and had less ureteral dilation ( P < 0.0001). Prestenting did not influence operative time ( P = 0.8534) or stone-free rates ( P = 0.2241). dURS patients were more likely to call the nurse; however, psURS versus dURS yielded no difference in return to the ED or readmission within 90 days. Conclusions: In this study, preoperative stenting offered few operative advantages and did not meaningfully influence returns to the ED and readmissions within 90 days after ureteroscopy.

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Receptors belonging to the Cys-loop gene superfamily of neurotransmittergated ion channels (e.g. acetylcholine, serotonin, GABA, and glycine receptors) mediate fast synaptic transmission. These receptors are targeted by a number of clinically used drugs (e.g. antiepileptics, antipsychotics, anesthetics). Cys-loop receptors contain three domains: extracellular (ECD), transmembrane (TMD), intracellular (ICD). The ECD and TMD have been studied in great detail and their 3-D structures have been determined. The recent identification of bacterial Cys-loop receptor homologues has propelled the structural knowledge to atomic resolution. However, all prokaryotic members lack the ICD. The ICD of metazoan Cys-loop receptors is the most diverse domain with respect to both length and amino-acid composition. The ICD therefore represents an attractive target for developing subtype-selective drugs with the promise of fewer side effects than drugs that target the highly-conserved ECD and TMD. We have engineered functional chimeras with ICDs from different eukaryotic receptors in the two-domain prokaryotic homologue GLIC (one chimera set published, Goyal, Salahudeen, Jansen, JBC 2011). Based on structure predictions others have hypothesized that the ICD is mainly unstructured, but contains an a-helical segment pre-TM4. We hypothesize based on computational results that cationic and anionic receptors have different ICD secondary structures, i.e., only cationic receptors contain an a-helical portion pre-TM4. For each eukaryotic ICD we generated 12 chimeras that differ by the linkers both N-and C-terminal to the inserted ICD. Interestingly, the number of functional chimeras in each set varies drastically between different ICDs. We are testing the functional consequences of inserting various ICDs using electrophysiological studies, and investigating the structure of the ICDs tethered to the TMD and at the lipid bilayer with spectroscopic and biochemical methods. 589-Pos Board B375Function of nAChRs Containing Alpha5 Subunits Neuronal nicotinic acetylcholine receptors (nAChRs) are abundantly expressed in the central nervous system. Neurons in several brain regions co-express alpha5, alpha4 and beta2 subunits. Changes in the receptor composition and stoichiometry of alpha4 and beta2 containing nAChRs are pertinent to disease states. Several genome-wide association and candidate gene studies have identified polymorphisms in the gene for the alpha5 subunit that are linked to an increased risk for nicotine addiction, alcohol addiction and lung cancer. However more information is required about the functional effects of incorporating a normal or mutated alpha5 subunit into the alpha4beta2 receptor pentamer. Here we examine differences in I-V relationships and dose-response relations between alpha4beta2 receptors and alpha4beta2 receptors including alpha5 subunits containing various mutations to the M2 domain expressed in Xenopus oocytes.