Histologic inflammation and collagen content are not positively correlated in human BPH.

INTRODUCTION: Recent clinical studies have implicated prostate inflammation and fibrosis in the development of bladder outlet obstruction and lower urinary tract symptoms (LUTS). Studies utilizing rodent models, including work in our laboratory, have shown prostate fibrosis to occur as a consequence of inflammation. However, the relationship between collagen content and inflammation in human tissue samples obtained from surgical treatment of benign prostatic hypererplasia (BPH)/LUTS has not to our knowledge been previously examined. METHODS: Prostate tissue specimens from 53 patients (ages 47-88, mean 65.1) treated by open simple prostatectomy or transurethral resection of the prostate for BPH/LUTS were stained to quantitatively assess prostate inflammation and collagen content. Patients with prostate cancer present in greater than 5% of the surgical specimen were excluded. Prostate volume was determined from pelvic CT scan obtained within 2 years of surgery. RESULTS: Analysis of the data showed that inflammation was inversely correlated with collagen content (r = -0.28, p = 0.04). In men with prostates less than 75 cm3 inflammation increases and collagen content decreases with prostate volume (p = 0.002 and p = 0.03, respectively) while in men with prostate volume over 75 cm3 inflammation decreases and collagen content increases with prostate volume (p = 0.30 and p = 0.005, respectively). CONCLUSIONS: Our data do not support the assumed positive association of prostate inflammation with collagen content. Coordinated analysis of scatter plots of inflammation and collagen content with prostate volume revealed a subset of prostates with volumes >50 cm3 prostate characterized by intense inflammation and low collagen content and it is this subgroup that appears most responsible for the inverse correlation of inflammation and collagen.

The influence of intermittent hypoxia, obesity, and diabetes on male genitourinary anatomy and voiding physiology.

We used male BTBR mice carrying the Lepob mutation, which are subject to severe and progressive obesity and diabetes beginning at 6 wk of age, to examine the influence of one specific manifestation of sleep apnea, intermittent hypoxia (IH), on male urinary voiding physiology and genitourinary anatomy. A custom device was used to deliver continuous normoxia (control) or IH to wild-type and Lepob/ob (mutant) mice for 2 wk. IH was delivered during the 12-h inactive (light) period in the form of 90 s of 6% O2 followed by 90 s of room air. Continuous room air was delivered during the 12-h active (dark) period. We then evaluated genitourinary anatomy and physiology. As expected for the type 2 diabetes phenotype, mutant mice consumed more food and water, weighed more, and voided more frequently and in larger urine volumes. They also had larger bladder volumes but smaller prostates, seminal vesicles, and urethras than wild-type mice. IH decreased food consumption and increased bladder relative weight independent of genotype and increased urine glucose concentration in mutant mice. When evaluated based on genotype (normoxia + IH), the incidence of pathogenic bacteriuria was greater in mutant mice than in wild-type mice, and among mice exposed to IH, bacteriuria incidence was greater in mutant mice than in wild-type mice. We conclude that IH exposure and type 2 diabetes can act independently and together to modify male mouse urinary function. NEW & NOTEWORTHY Metabolic syndrome and obstructive sleep apnea are common in aging men, and both have been linked to urinary voiding dysfunction. Here, we show that metabolic syndrome and intermittent hypoxia (a manifestation of sleep apnea) have individual and combined influences on voiding function and urogenital anatomy in male mice.

Histopathology of Anterior Urethral Strictures: Toward a Better Understanding of Stricture Pathophysiology.

PURPOSE: Histopathology can provide insights into disease mechanisms but to date it has been poorly described for urethral stricture. The purpose of this study was to comprehensively describe histopathological findings of stricture specimens obtained at the time of anterior urethroplasty. MATERIALS AND METHODS: All pathological specimens of men who underwent anterior urethroplasty of urethral stricture disease from 2010 to 2017 at a single institution were rereviewed by a single blinded pathologist directed to rule out lichen sclerosus and then describe inflammatory cell type and severity when present. Cohorts comprising strictures with no inflammation, minimal to mild inflammation or moderate to severe inflammation were developed and stricture, patient and surgical outcome characteristics were compared. RESULTS: Histopathology slides from 100 anterior urethroplasty cases were reviewed. Two or more lichen sclerosus characteristics were present in 21% of specimens and 44% of specimens showed chronic inflammation, which was minimal in 20%, mild in 39%, moderate in 39% and severe in 2%. Lymphocytes in 86% of specimens and plasma cells in 12% were the predominant cell types. Patients with inflammatory stricture reported worse overall health. Inflammation was largely absent from isolated bulbomembranous strictures (9%) and more common in lichen sclerosus strictures (100%). The 11% overall failure rate was not affected by the presence (7%) or absence (14%) of inflammation. CONCLUSIONS: Chronic inflammation is prevalent in a significant percent of urethral stricture disease specimens. Associations with worse overall health suggest systemic mediators. Absent inflammation in bulbomembranous strictures suggests a unique pathophysiology in this region. The presence of inflammation did not affect surgical outcomes at mid-term followup.

Extreme obesity does not predict poor cancer outcomes after surgery for renal cell cancer.

OBJECTIVE: To assess whether extreme obesity (body mass index [BMI] ≥ 40 kg/m(2) ) is associated with peri-operative outcomes, overall survival (OS), cancer-specific survival (CSS), or recurrence-free survival (RFS) after surgical treatment for renal cell carcinoma (RCC). PATIENTS AND METHODS: After institutional review board approval, we used an institutional database to identify patients treated surgically between January 2000 and December 2014 with a pathological diagnosis of RCC. Comprehensive clinical and pathological data were reviewed. Kaplan-Meier analyses were used to estimate OS, RFS and CSS. Univariate and multivariate Cox proportional hazards analysis was used to evaluate associations with OS, CSS and RFS in patients with extreme obesity, among other known predictive variables. RESULTS: In all, 100 patients (11.9%) with a BMI ≥ 40 kg/m(2) and 743 patients (88.1%) with a BMI < 40 kg/m(2) who were treated surgically for RCC were identified. Morbid obesity was not associated with an increased risk of blood transfusion (odds ratio [OR] 1, 95% confidence interval [CI] 0.587-1.70; P = 1.0). The median (interquartile range) length of hospital stay (LOS) was 4 (3-6) days. Morbid obesity was not associated with longer LOS (P = 0.26) or 30-day hospital readmission rates (P = 1.0). Major complications (Clavien ≥ 3a) were recorded in 67 patients (7.95%). BMI ≥ 40 kg/m(2) was not a predictor of major complications (OR 0.58, 95% CI 0.227-1.47; P = 0.251) or 90-day mortality (P = 0.4067). BMI ≥ 40 kg/m(2) was not associated with worse OS (P = 0.7), CSS (P = 0.2) or RFS (P = 0.5). BMI ≥ 35 kg/m(2) was also not associated with worse OS, CSS or RFS (P = 0.3, 0.1, 0.5, respectively). The 5-year OS rate was 68.9% for the entire cohort, including 69 and 70% for patients with BMI < 40 kg/m(2) and BMI ≥ 40 kg/m(2) , respectively (P = 0.69). The 5-year CSS was 79.5% for the entire cohort, including 78.4 and 87.9% (P = 0.16) for patients with BMI < 40 kg/m(2) and BMI ≥ 40 kg/m(2) , respectively. The 5-year RFS rates for BMI < 40 kg/m(2) and BMI ≥ 40 kg/m(2) were 84.1 and 90.6%, respectively (P = 0.48). CONCLUSIONS: Extreme obesity is not associated with worse peri-operative or cancer outcomes after surgery for RCC. Surgery should remain a standard treatment option in well selected morbidly obese patients.

Epac activation initiates associative odor preference memories in the rat pup.

Here we examine the role of the exchange protein directly activated by cAMP (Epac) in ß-adrenergic-dependent associative odor preference learning in rat pups. Bulbar Epac agonist (8-pCPT-2-O-Me-cAMP, or 8-pCPT) infusions, paired with odor, initiated preference learning, which was selective for the paired odor. Interestingly, pairing odor with Epac activation produced both short-term (STM) and long-term (LTM) odor preference memories. Training using ß-adrenergic-activation paired with odor recruited rapid and transient ERK phosphorylation consistent with a role for Epac activation in normal learning. An ERK antagonist prevented intermediate-term memory (ITM) and LTM, but not STM. Epac agonist infusions induced ERK phosphorylation in the mitral cell layer, in the inner half of the dendritic external plexiform layer, in the glomeruli and, patchily, among granule cells. Increased CREB phosphorylation in the mitral and granule cell layers was also seen. Simultaneous blockade of both ERK and CREB pathways prevented any long-term ß-adrenergic activated odor preference memory, while LTM deficits associated with blocking only one pathway were prevented by stronger ß-adrenergic activation. These results suggest that Epac and PKA play parallel and independent, as well as likely synergistic, roles in creating cAMP-dependent associative memory in rat pups. They further implicate a novel ERK-independent pathway in the mediation of STM by Epac.

Incidental Prostate Cancer Diagnosis Is Common After Holmium Laser Enucleation of the Prostate.

OBJECTIVE: To determine the incidence of incidental prostate cancer detection (iPCa) after holmium laser enucleation of the prostate (HoLEP). The published rate of iPCa after HoLEP is widely variable from 7% to 23% and we aim to define preoperative risk factors for iPCa to inform risk-adjusted preoperative evaluation for PCa. METHODS: Consecutive patients undergoing HoLEP from 2018 to 2022 were included and comprehensive clinical data abstracted from a prospectively maintained database. iPCa was defined as a diagnosis of PCa on pathologic examination of the HoLEP specimen. Patients with and without iPCa were compared with respect to preoperative clinical variables. RESULTS: Of 913 HoLEP patients, 183 (20%) were diagnosed with iPCa. Most patients (95%) had a preoperative prostate-specific antigen (PSA), 9% had negative MRI, and 30% had negative prostate biopsy. On multivariable analysis, PSA density (OR 1.06; 95% CI 1.03, 1.10; P < .001), preoperative biopsy status (OR 0.47, CI 0.30, 0.75; P = .002), and current 5-alpha reductase inhibitor use (OR 0.64, CI 0.43, 0.97; P = .034), were associated with iPCa diagnosis. CONCLUSION: In a significantly prescreened population, we identified a 20% rate of iPCa after HoLEP. Preoperative characteristics associated with iPCa diagnosis included increasing age, increasing PSA density, and current 5-alpha reductase inhibitor use. However, these factors alone may be of limited clinical utility to prospectively identify patients at high risk of iPCa diagnosis. We suggest and advocate for development of a standardized, risk-adapted evaluation focused on expanded use of imaging and selective biopsy to prioritize identification of clinically significant PCa prior to nononcologic surgery.

Modified Frailty Index predicts postoperative complications following adult-acquired buried penis surgery: A retrospective cohort study.

BACKGROUND: Given that patients with morbid obesity are predisposed to frailty, we sought to determine whether the 5-Factor Modified Frailty Index (mFI-5) predicts postoperative complications following surgery for adult-acquired buried penis, and secondarily, to compare the mFI-5 to body mass index (BMI) and American Society of Anesthesiologists (ASA) status as preoperative risk stratification measures. METHODS: We included all patients who underwent surgical management for adult-acquired buried penis at an academic Level I trauma center between 2015 and 2023. A manual chart review was performed to collect data on patient demographics, modified frailty index variables, intraoperative data, postoperative outcomes, and complications. RESULTS: A total of 55 patients underwent surgical repair of adult-acquired buried penis, with 26 experiencing postoperative complications (47.3%). Univariable regression analyses revealed that the mFI-5 was a significant predictor of postoperative complications (odds ratio [OR] 3.40, 95% confidence interval [CI]: 1.56-7.42, p = .002), ongoing postoperative urinary problems (OR 2.03, 95% CI: 1.02-4.05, p = .045), patient dissatisfaction with outcomes (OR 3.29, 95% CI: 1.35-8.02, p = .009), and persistent postoperative symptoms (OR 2.42, 95% CI: 1.10-5.35, p = .029). There was no significant association between ASA classification and postoperative complications (OR 1.59, 95% CI:.544-4.63, p = .398). Multivariable analysis demonstrated that the mFI-5 was an independent predictor of postoperative complications (OR 5.34, 95% CI: 1.80-15.9, p = .003) when controlling for BMI and age. CONCLUSION: The mFI-5 is an independent predictor of postoperative complications in patients undergoing surgical repair of adult-acquired buried penis. The simplicity of the index permits efficient preoperative risk stratification of adult-acquired buried penis patients and provides important counseling information that may not be reflected by age or BMI alone.

PKA increases in the olfactory bulb act as unconditioned stimuli and provide evidence for parallel memory systems: pairing odor with increased PKA creates intermediate- and long-term, but not short-term, memories.

Neonatal odor-preference memory in rat pups is a well-defined associative mammalian memory model dependent on cAMP. Previous work from this laboratory demonstrates three phases of neonatal odor-preference memory: short-term (translation-independent), intermediate-term (translation-dependent), and long-term (transcription- and translation-dependent). Here, we use neonatal odor-preference learning to explore the role of olfactory bulb PKA in these three phases of mammalian memory. PKA activity increased normally in learning animals 10 min after a single training trial. Inhibition of PKA by Rp-cAMPs blocked intermediate-term and long-term memory, with no effect on short-term memory. PKA inhibition also prevented learning-associated CREB phosphorylation, a transcription factor implicated in long-term memory. When long-term memory was rescued through increased ß-adrenoceptor activation, CREB phosphorylation was restored. Intermediate-term and long-term, but not short-term odor-preference memories were generated by pairing odor with direct PKA activation using intrabulbar Sp-cAMPs, which bypasses ß-adrenoceptor activation. Higher levels of Sp-cAMPs enhanced memory by extending normal 24-h retention to 48-72 h. These results suggest that increased bulbar PKA is necessary and sufficient for the induction of intermediate-term and long-term odor-preference memory, and suggest that PKA activation levels also modulate memory duration. However, short-term memory appears to use molecular mechanisms other than the PKA/CREB pathway. These mechanisms, which are also recruited by ß-adrenoceptor activation, must operate in parallel with PKA activation.

Collagen is More Abundant and Structurally Altered in Lichen Sclerosus.

OBJECTIVE: To test the hypothesis that genital skin and male urethra affected by lichen sclerosus (LS) has increased collagen content and altered collagen structure. METHODS: We used picrosirius red to stain and image collagen in human urethral, vulvar, and foreskin specimens with and without LS. Using Image J software, we quantified and compared (1) collagen content (using 2o metrics: collagen proportionate area [CPA] and collagen fiber count), (2) collagen fiber length and width, and (3) collagen structure using the texture analysis technique gray level co-localization matrix (GLCM) with respect to LS status and tissue type. RESULTS: We analyzed 23 LS specimens (vulva n=9, urethra n=7, foreskin n=7) and 29 non-LS specimens (vulva n=9, urethra n=7, foreskin n=13). Fiber count and CPA were significantly higher in all LS specimens compared to non-LS specimens (CPA: mean±SD 0.971±0.03 vs 0.948±0.02, P < .007; fiber count: mean±SD = 2906±127 vs 2509±78 fibers; P = .003). Collagen fiber width and length were similar with respect to LS status. GLCM analysis showed decreased inverse difference moment and increased entropy in LS tissues indicative of less homogeneous and more disorganized tissue structure (P<.001). CONCLUSION: LS tissues have greater collagen content compared to non-LS tissues. Quantitative assessment of collagen organization, using GLCM, revealed less homogeneity and more disorganization of collagen in LS compared to non-LS tissues. Taken together, our findings suggest that alterations in physical tissue properties seen in LS may be due to both increased collagen abundance and altered structure.

"Postoperative Outcomes Following Buried Penis Reconstruction: A Single-Institution Experience Using the Wisconsin Classification System".

BACKGROUND: Adult acquired buried penis (AABP) is a complex condition often necessitating surgical intervention. This study seeks to examine the validity of the Wisconsin Classification System (WCS) in guiding the surgical management of AABP. Additionally, we aimed to identify which factors contribute to postoperative complications and persistent symptoms following AABP repair. METHODS: We retrospectively reviewed all patients who underwent surgical repair of AABP from 2015-2021 by the senior author at our institution. Patients were categorized according to anatomic characteristics using the WCS. Preoperative symptoms, postoperative symptoms, and postoperative complications were evaluated. RESULTS: Fifty-two patients underwent AABP repair. The mean age was 56.5±14.8 years, and the mean duration of follow-up was 350.0±517.4 days. The assigned preoperative WCS score was congruent with operative management in most patients (86.0%). Morbid obesity (BMI>40.0kg/m2) and postoperative complications were associated with persistent symptoms following AABP repair (p=0.026 and p=0.021, respectively). Increased WCS score was not associated with persistent postoperative symptoms (p=0.314). Morbid obesity (p=0.003), diabetes (p=0.029) and having a panniculectomy during AABP repair (p=0.046) increased the odds for developing postoperative complications. Patients with Type I AABP had significantly fewer complications than those with Type II, III, or IV (p=0.032). CONCLUSIONS: The Wisconsin Classification System serves as a preoperative guide, an educational tool for patients, and provides a framework for the discussion of intraoperative maneuvers and the likelihood of complications. It is imperative to counsel patients on the surgical management of AABP and the postoperative course, as this may permit realistic patient expectations and optimize outcomes.

Expansion of variant diversity associated with a high prevalence of pathogen strain superinfection under conditions of natural transmission.

Superinfection occurs when a second, genetically distinct pathogen strain infects a host that has already mounted an immune response to a primary strain. For antigenically variant pathogens, the primary strain itself expresses a broad diversity of variants over time. Thus, successful superinfection would require that the secondary strain express a unique set of variants. We tested this hypothesis under conditions of natural transmission in both temperate and tropical regions where, respectively, single-strain infections and strain superinfections of the tick-borne pathogen Anaplasma marginale predominate. Our conclusion that strain superinfection is associated with a significant increase in variant diversity is supported by progressive analysis of variant composition: (i) animals with naturally acquired superinfection had a statistically significantly greater number of unique variant sequences than animals either experimentally infected with single strains or infected with a single strain naturally, (ii) the greater number of unique sequences reflected a statistically significant increase in primary structural diversity in the superinfected animals, and (iii) the increase in primary structural diversity reflected increased combinations of the newly identified hypervariable microdomains. The role of population immunity in establishing temporal and spatial patterns of infection and disease has been well established. The results of the present study, which examined strain structure under conditions of natural transmission and population immunity, support that high levels of endemicity also drive pathogen divergence toward greater strain diversity.

Two mutations associated with macrolide resistance in Treponema pallidum: increasing prevalence and correlation with molecular strain type in Seattle, Washington.

BACKGROUND: Although azithromycin promised to be a safe and effective single-dose oral treatment of early syphilis, azithromycin treatment failure has been documented and is associated with mutations in the 23S rDNA of corresponding Treponema pallidum strains. The prevalence of strains harboring these mutations varies throughout the United States and the world. We examined T. pallidum strains circulating in Seattle, Washington, from 2001 to 2010 to determine the prevalence of 2 mutations associated with macrolide resistance and to determine whether these mutations were associated with certain T. pallidum strain types. METHODS: Subjects were enrolled in a separate ongoing study of cerebrospinal fluid abnormalities in patients with syphilis. T. pallidum DNA purified from blood and T. pallidum strains isolated from blood or cerebrospinal fluid were analyzed for two 23S rDNA mutations and for the molecular targets used in an enhanced molecular stain typing system. RESULTS: Nine molecular strain types of T. pallidum were identified in Seattle from 2001 to 2010. Both macrolide resistance mutations were identified in Seattle strains, and the prevalence of resistant T. pallidum exceeded 80% in 2005 and increased through 2010. Resistance mutations were associated with discrete molecular strain types of T. pallidum. CONCLUSIONS: Macrolide-resistant T. pallidum strains are highly prevalent in Seattle, and each mutation is associated with discrete strain types. Macrolides should not be considered for treatment of syphilis in regions where prevalence of the mutations is high. Combining the resistance mutations with molecular strain typing permits a finer analysis of the epidemiology of syphilis in a community.

Odor preference learning and memory modify GluA1 phosphorylation and GluA1 distribution in the neonate rat olfactory bulb: testing the AMPA receptor hypothesis in an appetitive learning model.

An increase in synaptic AMPA receptors is hypothesized to mediate learning and memory. AMPA receptor increases have been reported in aversive learning models, although it is not clear if they are seen with memory maintenance. Here we examine AMPA receptor changes in a cAMP/PKA/CREB-dependent appetitive learning model: odor preference learning in the neonate rat. Rat pups were given a single pairing of peppermint and 2 mg/kg isoproterenol, which produces a 24-h, but not a 48-h, peppermint preference in the 7-d-old rat pup. GluA1 PKA-dependent phosphorylation peaked 10 min after the 10-min training trial and returned to baseline within 90 min. At 24 h, GluA1 subunits did not change overall but were significantly increased in synaptoneurosomes, consistent with increased membrane insertion. Immunohistochemistry revealed a significant increase in GluA1 subunits in olfactory bulb glomeruli, the targets of olfactory nerve axons. Glomerular increases were seen at 3 and 24 h after odor exposure in trained pups, but not in control pups. GluA1 increases were not seen as early as 10 min after training and were no longer observed 48 h after training when odor preference is no longer expressed behaviorally. Thus, the pattern of increased GluA1 membrane expression closely follows the memory timeline. Further, blocking GluA1 insertion using an interference peptide derived from the carboxyl tail of the GluA1 subunit inhibited 24 h odor preference memory providing causative support for our hypothesis. PKA-mediated GluA1 phosphorylation and later GluA1 insertion could, conjointly, provide increased AMPA function to support both short-term and long-term appetitive memory.

A systematic approach for successful repair of radiated and non-radiated ureteral injuries.

BACKGROUND: Successful ureteral reconstruction is challenging, particularly in radiated fields. We characterize and directly compare surgical outcomes in modern cohorts of radiated and non-radiated patients undergoing ureteral reconstruction utilizing a systematic approach to pre-operative assessment. We hypothesize that radiated patients will undergo more complex ureteral reconstructions and experience higher rates of surgical failure and complications compared to nonradiated patients. METHODS: Consecutive cases of ureteral reconstruction for acquired ureteral injury performed by a single surgeon from 2010-2018 were retrospectively reviewed. Clinical data were collected including pre-operative bladder capacity, ureteral injury characteristics, and surgical technique. Ileal ureter and autotransplantation were classified as "complex" ureteral repairs, and surgical success was defined as freedom from surgical revision of the ureteral anastomosis and/or ureteral stenting. RESULTS: There were 47 ureteral reconstructions performed including 17 (36%) radiated patients. Radiated patients had lower pre-operative bladder capacity and were more likely to undergo complex repairs compared to non-radiated patients (35% vs. 7%, P=0.01). Overall surgical success was high (98%) and similar between radiated (94%) and non-radiated groups (100%) at median follow up of 30 months. Clavien grade 3-4 complications occurred in 18% of radiated and 10% of non-radiated patients (P=0.48). CONCLUSIONS: Careful pre-operative evaluation and appropriate selection of surgical technique facilitates high and similar success of ureteral reconstruction in radiated and non-radiated patients. Complex ureteral repairs were more common in radiated patients, however the majority of radiated ureteral injuries (65%) were reconstructed without tissue transfer. Radiated patients had lower pre-operative bladder capacities, but similar surgical morbidity, renal function, and persistent urge incontinence compared to non-radiated patients.

Effect of Metabolic Syndrome on Anatomy and Function of the Lower Urinary Tract Assessed on MRI.

OBJECTIVE: To investigate the relationship between metabolic syndrome (MetS) and lower urinary tract symptoms (LUTS) with functional and anatomic changes of the lower urinary tract with MRI. MATERIALS AND METHODS: The bladder and prostate of 95 subjects (56M, 39F) were segmented on T2-weighted pelvic MRI using Materialize Mimics 3D software. Bladder wall volume (BWV), post-void residual (PVR) and prostate volume (PV) were quantified from the 3D renderings. LUTS were quantified using validated questionnaires administered at the time of MRI. Wilcoxin rank sum, win ratio and chi-square tests were used to correlate symptom scores, BWV, PVR and PV in patients 1) without vs with MetS, 2) with mild (IPSS or UDI-6: 0-7) vs moderate-severe (IPSS: 8-35 or UDI-6: ≥8) and 3) normal vs enlarged prostates (>40cm3). Multivariate linear regression was used to determine predictors for BWV, PVR and PV. RESULTS: Men with MetS had increased BWV (66.8 vs 51.1cm3, P = .003), higher PVR (69.1 vs 50.5cc, P= .05) and increased PV (67.2 vs 40.1cm3, P= .01). Women without and with MetS had similar BWV, PVR and LUTS (P= .3-.78). There was no difference in prevalence of MetS, BWV, PVR or PV in men or women with mild vs moderate-severe LUTS (P = .26-.97). Men with enlarged prostates were more likely to have MetS (P = .003). There was no difference in BWV, PVR and LUTS for men with normal vs enlarged prostates (P= .44-.94). In men, BWV was highly correlated with MetS (P = .005) on regression analysis. CONCLUSION: MetS leads to detrusor hypertrophy and may contribute to impaired bladder function, likely related to the effect on the prostate.

Mammalian intermediate-term memory: new findings in neonate rat.

The ability of anisomycin, a translation inhibitor, and actinomycin, a transcription inhibitor to disrupt a cAMP/PKA-dependent odor preference memory in neonate rat was examined. Previous reports in invertebrates had described a novel translation-dependent intermediate-term memory dissected with these inhibitors, but similar effects have not been reported in mammalian memory systems. When anisomycin was infused into the olfactory bulb after the pairing of peppermint odor and the ß-adrenoceptor agonist isoproterenol (2mg/kg), short-term memory (1 or 3h) was intact, but intermediate (5h) and long-term (24h) memory was disrupted. When actinomycin was infused, only long-term memory was disrupted. This pattern of results is consistent with that reported in invertebrates for intermediate-term memory and led us to try a lower level of the unconditioned stimulus (isoproterenol) to isolate intermediate-term memory from long-term memory. Pups given a dose of 1.5mg/kg isoproterenol paired with peppermint odor showed memory for peppermint 5h, but not 24h, after training. These observations in the rat pup olfactory system parallel short-, intermediate- and long-term memory characteristics previously described in invertebrates. Odor preference memory in neonate rodents offers a tool to increase our understanding of the properties and mechanisms of multi-phasic memory in mammals.

Cluster analysis of men undergoing surgery for BPH/LUTS reveals prominent roles of both bladder outlet obstruction and diminished bladder contractility.

Lower urinary tract symptoms (LUTS) in aging men are commonly attributed to bladder outlet obstruction from benign prostatic hyperplasia (BPH) but BPH/LUTS often reflects a confluence of many factors. We performed a hierarchical cluster analysis using four objective patient characteristics (age, HTN, DM, and BMI), and five pre-operative urodynamic variables (volume at first uninhibited detrusor contraction, number of uninhibited contractions, Bladder Outlet Obstruction Index (BOOI), Bladder Contractility Index (BCI) and Bladder Power at Qmax) to identify meaningful subgroups within a cohort of 94 men undergoing surgery for BPH/LUTS. Two meaningful subgroups (clusters) were identified. Significant differences between the two clusters included Prostate Volume (95 vs 53 cc; p-value = 0.001), BOOI (mean 70 vs 49; p-value = 0.001), BCI (mean 129 vs 83; p-value <0.001), Power (689 vs 236; p-value <0.001), Qmax (8.3 vs 4.9 cc/sec; p-value <0.001) and post-void residual (106 vs 250 cc; p-value = 0.001). One cluster is distinguished by larger prostate volume, greater outlet resistance and better bladder contractility. The other is distinguished by smaller prostate volume, lower outlet resistance and worse bladder contractility. Remarkably, the second cluster exhibited greater impairment of urine flow and bladder emptying. Surgery improved flow and emptying for patients in both clusters. These findings reveal important roles for both outlet obstruction and diminished detrusor function in development of diminished urine flow and impaired bladder emptying in patients with BPH/LUTS.

A mechanism linking perinatal 2,3,7,8 tetrachlorodibenzo-p-dioxin exposure to lower urinary tract dysfunction in adulthood.

Benign prostatic hyperplasia/lower urinary tract dysfunction (LUTD) affects nearly all men. Symptoms typically present in the fifth or sixth decade and progressively worsen over the remainder of life. Here, we identify a surprising origin of this disease that traces back to the intrauterine environment of the developing male, challenging paradigms about when this disease process begins. We delivered a single dose of a widespread environmental contaminant present in the serum of most Americans [2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD), 1 µg/kg], and representative of a broader class of environmental contaminants, to pregnant mice and observed an increase in the abundance of a neurotrophic factor, artemin, in the developing mouse prostate. Artemin is required for noradrenergic axon recruitment across multiple tissues, and TCDD rapidly increases prostatic noradrenergic axon density in the male fetus. The hyperinnervation persists into adulthood, when it is coupled to autonomic hyperactivity of prostatic smooth muscle and abnormal urinary function, including increased urinary frequency. We offer new evidence that prostate neuroanatomical development is malleable and that intrauterine chemical exposures can permanently reprogram prostate neuromuscular function to cause male LUTD in adulthood.