Julian Hanske

Pannexin1 stabilizes synaptic plasticity and is needed for learning.

Pannexin 1 (Panx1) represents a class of vertebrate membrane channels, bearing significant sequence homology with the invertebrate gap junction proteins, the innexins and more distant similarities in the membrane topologies and pharmacological sensitivities with gap junction proteins of the connexin family. In the nervous system, cooperation among pannexin channels, adenosine receptors, and KATP channels modulating neuronal excitability via ATP and adenosine has been recognized, but little is known about the significance in vivo. However, the localization of Panx1 at postsynaptic sites in hippocampal neurons and astrocytes in close proximity together with the fundamental role of ATP and adenosine for CNS metabolism and cell signaling underscore the potential relevance of this channel to synaptic plasticity and higher brain functions. Here, we report increased excitability and potently enhanced early and persistent LTP responses in the CA1 region of acute slice preparations from adult Panx1−/− mice. Adenosine application and N-methyl-D-aspartate receptor (NMDAR)-blocking normalized this phenotype, suggesting that absence of Panx1 causes chronic extracellular ATP/adenosine depletion, thus facilitating postsynaptic NMDAR activation. Compensatory transcriptional up-regulation of metabotropic glutamate receptor 4 (grm4) accompanies these adaptive changes. The physiological modification, promoted by loss of Panx1, led to distinct behavioral alterations, enhancing anxiety and impairing object recognition and spatial learning in Panx1−/− mice. We conclude that ATP release through Panx1 channels plays a critical role in maintaining synaptic strength and plasticity in CA1 neurons of the adult hippocampus. This result provides the rationale for in-depth analysis of Panx1 function and adenosine based therapies in CNS disorders.

Racial Differences in the Surgical Care of Medicare Beneficiaries With Localized Prostate Cancer

IMPORTANCE There is extensive evidence suggesting that black men with localized prostate cancer (PCa) have worse cancer-specific mortality compared with their non-Hispanic white counterparts. OBJECTIVE To evaluate racial disparities in the use, quality of care, and outcomes of radical prostatectomy (RP) in elderly men (≥ 65 years) with nonmetastatic PCa. DESIGN, SETTING, AND PARTICIPANTS This retrospective analysis of outcomes stratified according to race (black vs non-Hispanic white) included 2020 elderly black patients (7.6%) and 24,462 elderly non-Hispanic white patients (92.4%) with localized PCa who underwent RP within the first year of PCa diagnosis in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database between 1992 and 2009. The study was performed in 2014. MAIN OUTCOMES AND MEASURES Process of care (ie, time to treatment, lymph node dissection), as well as outcome measures (ie, complications, emergency department visits, readmissions, PCa-specific and all-cause mortality, costs) were evaluated using Cox proportional hazards regression. Multivariable conditional logistic regression and quantile regression were used to study the association of racial disparities with process of care and outcome measures. RESULTS The proportion of black patients with localized prostate cancer who underwent RP within 90 days was 59.4% vs 69.5% of non-Hispanic white patients (P <  001). In quantile regression of the top 50% of patients, blacks had a 7-day treatment delay compared with non-Hispanic whites. (P <  001). Black patients were less likely to undergo lymph node dissection (odds ratio [OR], 0.76 [95% CI, 0.66-0.80]; P < .001) but had higher odds of postoperative visits to the emergency department (within 30 days: OR, 1.48 [95% CI, 1.18-1.86]); after 30 days or more (OR, 1.45 [95% CI, 1.19-1.76]) and readmissions (within 30 days: OR, 1.28 [95% CI, 1.02-1.61]); ≥ 30 days (OR, 1.27 [95% CI, 1.07-1.51]) compared with non-Hispanic whites. The surgical treatment of black patients was associated with a higher incremental annual cost (the top 50% of blacks spent

Differences in Prostate-Specific Antigen Testing Among Urologists and Primary Care Physicians Following the 2012 USPSTF Recommendations

1185.50 (95% CI ,

The Effect of Resident Involvement on Perioperative Outcomes in Transurethral Urologic Surgeries

804.85-1

Temporal trends in receipt of adequate lymphadenectomy in bladder cancer 1988 to 2010

1566.10; P < .001) more than the top 50% of non-Hispanic whites). There was no difference in PCa-specific mortality (P = .16) or all-cause mortality (P = .64) between black and non-Hispanic white men. CONCLUSIONS AND RELEVANCE Blacks treated with RP for localized PCa are more likely to experience adverse events and incur higher costs compared with non-Hispanic white men; however, this does not translate into a difference in PCa-specific or all-cause mortality.

Unified patch clamp protocol for the characterization of Pannexin 1 channels in isolated cells and acute brain slices

patients relating to their use. In addition, including CAM physicians in groups such as accountable care organizations can improve communication between physicians and streamline patient records.5 Clinical and organizational incentives that encourage patient disclosure of CAM use may facilitate better coordination of care, reduce the risk of adverse interactions between conventional medications and CAM products, and lead to better patient outcomes.

The influence of marital status on the use of breast, cervical, and colorectal cancer screening.

OBJECTIVE To conduct the first study of intra- and postoperative outcomes related to intraoperative resident involvement in transurethral resection procedures for benign prostatic hyperplasia and bladder cancer in a large, multi-institutional database. DESIGN Relying on the American College of Surgeons National Surgical Quality Improvement Program Participant User Files (2005-2012), we abstracted all cases of endoscopic prostate surgery (EPS) for benign prostatic hyperplasia and transurethral resection of bladder tumors (TURBTs). Multivariable logistic regression models were constructed to assess the effect of trainee involvement (postgraduate year [PGY] 1-2: junior, PGY 3-4: senior, PGY ≥ 5: chief or fellow) vs attending only on operative time and length of hospital stay, as well as 30-day complication, reoperation, and readmission rates. RESULTS In all, 5093 EPS and 3059 TURBTs for a total of 8152 transurethral resection procedures were performed during the study period for which data on resident involvement were available. In multivariable analyses, resident involvement in EPS or TURBT was associated with increased odds of prolonged operative times and hospital readmissions in 30 days independent of resident level of training. Resident involvement was not associated with overall complications or reoperation rates. CONCLUSIONS Resident involvement in lower urinary tract surgeries is associated with increased readmissions. Strategies to optimize resident teaching of these common urologic procedures in order to minimize possible risks to patients should be explored.

Asian Americans and prostate cancer: A nationwide population-based analysis

INTRODUCTION AND OBJECTIVE The importance of pelvic lymphadenectomy (LND) for diagnostic and therapeutic purposes at the time of radical cystectomy (RC) for bladder cancer is well documented. Although some debate remains on the optimal number of lymph nodes removed, 10 nodes has been proposed as constituting an adequate LND. We used data from the Surveillance, Epidemiology, and End Results database to examine predictors and temporal trends in the receipt of an adequate LND at the time of RC for bladder cancer. MATERIAL AND METHODS Within the Surveillance, Epidemiology, and End Results database, we extracted data on all patients with nonmetastatic bladder cancer receiving RC in the years 1988 to 2010. First, we assess the proportion of individuals undergoing RC who received an adequate LND (≥10 nodes removed) over time. Second, we calculate odds ratios (ORs) of receiving an adequate LND using logistic regression modeling to compare study periods. Covariates included sex, race, age, region, tumor stage, urban vs. rural location, and insurance status. RESULTS Among the 5,696 individuals receiving RC during the years 1988 to 2010, 2,576 (45.2%) received an adequate LND. Over the study period, the proportion of individuals receiving an adequate LND increased from 26.4% to 61.3%. The odds of receiving an adequate LND increased over the study period; a patient undergoing RC in 2008 to 2010 was over 4-fold more likely to receive an adequate LND relative to a patient treated in 1988 to 1991 (OR = 4.63, 95% CI: 3.32-6.45). In addition to time of surgery, tumor stage had a positive association with receipt of adequate LND (OR = 1.49 for stage IV [T4 N1 or N0] vs. stage I [T1 or Tis], 95% CI: 1.22-1.82). Age, sex, marital status, and race were not significant predictors of adequate LND. CONCLUSION Adequacy of pelvic LND remains an important measure of surgical quality in bladder cancer. Our data show that over the years 1988 to 2010, the likelihood of receiving an adequate LND has increased substantially; however, a substantial minority of patients still does not receive LND. Further study into factors leading to adequate LND is needed to increase the use of this important technique.

Contemporary nationwide patterns of self-reported prostate-specific antigen screening in US veterans.

In the central nervous system, Pannexin 1 (Panx1) channels are implicated in a variety of physiological and pathological conditions. One of the prerequisites to enlighten the role of Panx1 is the development and standardization of reliable methods. Here, we address the applicability of voltage clamp protocols to identify Panx1 channel mediated currents in neurons of acutely dissected brain slices. We improved an established protocol and report on a modified paradigm that robustly evokes Panx1 channel currents. Crucial advances are the use of physiologic ion gradient conditions and a preconditioning step of depolarizing membrane potential ramps of long duration. This new paradigm provides significant impact on membrane current generation at hypo- and depolarized holding potential steps post voltage ramp preconditioning in heterologous expression systems and primary hippocampal CA1 neurons of mouse brain slices in vitro. Finally, we demonstrate that under these conditions the analysis of tail currents elicited by repolarization of the cells from preconditioning holding potential depolarization permits an independent method to isolate Panx1 mediated channel activity. In summary, this study provides a comprehensive methodological improvement in the biophysical analysis of Panx1 channels with a particular focus on investigations under physiological conditions in complex tissues.

Wound dehiscence in a sample of 1 776 cystectomies: identification of predictors and implications for outcomes.

PURPOSE To examine the impact of marital status on the use of screening for breast, cervical, and colorectal cancer. METHODS We relied on 2012 Behavioral Risk Factor Surveillance System Survey age-appropriate screening cohorts. Appropriate screening for breast, cervical, and colorectal cancer was determined according to United States Preventive Services Task Force recommendations in effect at the time of the 2012 survey. Complex samples logistic regression models were performed to examine the effect of marital status on cancer screening. RESULTS Overall, 81.6, 83.9, and 68.9% of married participants underwent breast, cervical, and colorectal cancer, respectively, relative to 74.2, 75.1, and 60.9% for divorced/widowed/separated, individuals, and 74.7, 78.7, and 53.4% for never married individuals. Marital status (married vs. never married) was an independent predictor of screening for all cancers examined: breast cancer, odds ratio (OR): 1.42 (95% confidence interval [CI]: 1.25-1.61); cervical cancer, OR: 1.29 (95% CI: 1.16-1.43); colorectal cancer, OR: 1.63 (95% CI: 1.51-1.77). Gender-specific subgroup analyses for colorectal cancer suggests that marital status may exert a greater effect in men, relative to women (married men: OR 1.75, 95% CI: 1.56-1.96; married women: OR: 1.52, 95% CI: 1.35-1.70). CONCLUSION Being married is associated with increased utilization of breast, cervical, and colorectal cancer screening. The influence of marital status was greater in men relative to women eligible for colorectal cancer screening. Our results emphasize the importance of social determinants of health-seeking behaviors.