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This research used the Revised Universal Soil Loss Equation (RUSLE) with Sediment Delivery Ratio (SDR) model. The analytic hierarchy process (AHP) method, while also incorporating the use of a geographic information system (GIS) and remote sensing (RS) to predict the annual soil loss rate and spatialise the processes of water erosion at the scale of the Loukkos Watershed, Morocco. The RUSLE model and AHP parameters were estimated using RS data, and the erosion vulnerability zones were determined using GIS. We used five parameters, including precipitation erosivity, soil erodibility, slope length and steepness, vegetation cover, and soil erosion control practices in the RUSLE. For the AHP technique, we used seven geo‐environmental factors, including annual average precipitation, drainage density, lineament density, slope, soil texture, land use/land cover and landform maps. The results of RUSLE indicated that the average annual soil loss varied from 0 to 2388.27 t·ha−1·year−1. The total estimated annual potential soil loss was approximately 40 790 220.11 t·ha−1·year−1, and a sediment yield estimated by RUSLE‐SDR was 8 647 526.66 t·ha−1·year−1, equivalent to 6.65 Mm3. This value is very close to the measured value of 6.81 Mm3, for a difference of 0.16 Mm3. Furthermore, the results of the AHP indicate that the soil erosion potential index varies from 0 to 0.205315 t·ha−1·year−1. Overall, nearly 13.7% of the area suffered from severe soil erosion exceeding 50 t·ha−1·year−1. Approximately 80% of the Loukkos Watershed area experienced only slight erosion, while the remaining 6% incurred moderate erosion. Integrating GIS and RS into the RUSLE model and AHP helped us robustly estimate the extent and degree of erosion risk. Territorial decision‐makers should adopt our results to develop soil conservation strategies, water management plans and other necessary soil and water conservation measures for this region. [ABSTRACT FROM AUTHOR]

Simple Summary: In our paper, we examine various facets of prostate cancer lung metastasis. We explore their clinical manifestations, such as respiratory symptoms and potential complications. Diagnostic modalities, including imaging techniques and biomarker analysis, are scrutinized for accurate identification. Treatment strategies, encompassing surgery, radiation therapy, chemotherapy, and targeted therapies, are discussed for their efficacy. Survival outcomes are assessed to gauge the effectiveness of different interventions. Through comprehensive analysis, we aim to provide insights into managing prostate cancer lung metastasis and enhancing patient care and outcomes. Prostate cancer lung metastasis represents a clinical conundrum due to its implications for advanced disease progression and the complexities it introduces in treatment planning. As the disease progresses to distant sites such as the lung, the clinical management becomes increasingly intricate, requiring tailored therapeutic strategies to address the unique characteristics of metastatic lesions. This review seeks to synthesize the current state of knowledge surrounding prostate cancer metastasis to the lung, shedding light on the diverse array of clinical presentations encountered, ranging from subtle radiological findings to overt symptomatic manifestations. By examining the diagnostic modalities utilized in identifying this metastasis, including advanced imaging techniques and histopathological analyses, this review aims to provide insights into the diagnostic landscape and the challenges associated with accurately characterizing lung metastatic lesions in prostate cancer patients. Moreover, this review delves into the nuances of therapeutic interventions employed in managing prostate cancer lung metastasis, encompassing systemic treatments such as hormonal therapies and chemotherapy, as well as metastasis-directed therapies including surgery and radiotherapy. [ABSTRACT FROM AUTHOR]

Background: Patients with high-risk prostate cancer (HRPC) have multiple accepted treatment options. Because there is no overall survival benefit of one option over another, appropriate treatment must consider patient life expectancy, quality of life, and cost.Methods: The authors compared quality-adjusted life years (QALYs) and cost effectiveness among treatment options for HRPC using a Markov model with three treatment arms: (1) external-beam radiotherapy (EBRT) delivered with 20 fractions, (2) EBRT with 23 fractions followed by low-dose-rate (LDR) brachytherapy boost, or (3) radical prostatectomy alone. An exploratory analysis considered a simultaneous integrated boost according to the FLAME trial (ClinicalTrials.gov identifier NCT01168479).Results: Treatment strategies were compared using the incremental cost-effectiveness ratio (ICER). EBRT with LDR brachytherapy boost was a cost-effective strategy (ICER, $20,929 per QALY gained). These results were most sensitive to variations in the biochemical failure rate. However, the results still demonstrated cost effectiveness for the brachytherapy boost paradigm, regardless of any tested parameter ranges. Probabilistic sensitivity analysis demonstrated that EBRT with LDR brachytherapy was favored in 52% of 100,000 Monte Carlo iterations. In an exploratory analysis, EBRT with a simultaneous integrated boost was also a cost-effective strategy, resulting in an ICER of $62,607 per QALY gained; however, it was not cost effective compared with EBRT plus LDR brachytherapy boost.Conclusions: EBRT with LDR brachytherapy boost may be a cost-effective treatment strategy compared with EBRT alone and radical prostatectomy for HRPC, demonstrating high-value care. The current analysis suggests that a reduction in biochemical failure alone can result in cost-effective care, despite no change in overall survival. [ABSTRACT FROM AUTHOR]

Objectives: The objective was to evaluate the diagnostic performance of surveillance11 C-choline positron emission tomography/computed tomography (PET/CT) for the detection of disease relapse in patients with a history of biochemically recurrent (BCR) prostate cancer (PCa) and prostate-specific antigen (PSA) ≤0.1 ng/ml.Materials and Methods: We included patients who had been treated for BCR PCa and had a surveillance11 C-choline PET/CT at serum PSA ≤0.1 ng/ml. Positive surveillance PET/CT was defined as a study that identified a new tracer-avid lesion or new tracer uptake in a previously treated lesion or both. Findings were confirmed against a composite radiologic-pathologic gold standard. Time to recurrence association analyses were performed for disease relapse risk with the use of Cox proportional hazards regression.Results: In total, 13 (12.1%) of the 107 patients had positive surveillance PET/CT scans, confirmed on pathologic assessment (n = 5) and subsequent imaging (n = 8). Among these 13 patients, ten had distant metastases, two had local recurrence, and one had both. Nine of the ten patients with metastases had oligometastatic disease defined as the presence of ≤3 metastases. Serum PSA became detectable again in only seven patients with positive surveillance PET/CT, after a mean interval from surveillance PET/CT of 292 days (range: 105-543 days). We identified an association of N stage with increased risk of recurrence (hazard ratio = 3.85; P = 0.036) although this was not significant after accounting for multiple testing.Conclusions: Surveillance11 C-choline PET/CT can detect early disease relapse at serum PSA ≤0.1 ng/ml in patients with a history of BCR PCa. [ABSTRACT FROM AUTHOR]

Purpose: To prospectively assess acute differences in patient‐reported outcomes in bowel and urinary domains between intensity‐modulated radiotherapy (IMRT) and proton beam therapy (PBT) for prostate cancer. Methods and Materials: Bowel function (BF), urinary irritative/obstructive symptoms (UO), and urinary incontinence (UI) domains of EPIC‐26 were collected in patients with T1‐T2 prostate cancer receiving IMRT or PBT at a tertiary cancer center (2015‐2018). Mean changes in domain scores were analyzed from pretreatment to the end of and 3 months post‐radiotherapy for each modality. A clinically meaningful change was defined as a score change >50% of the baseline standard deviation. Results: A total of 157 patients receiving IMRT and 105 receiving PBT were included. There were no baseline differences in domain scores between cohorts. At the end of radiotherapy, there was significant and clinically meaningful worsening of BF and UO scores for patients receiving either modality. In the BF domain, the IMRT cohort experienced greater decrement (−13.0 vs −6.7, P <.01), and had a higher proportion of patients with clinically meaningful reduction (58.4% vs 39.5%, P =.01), compared to PBT. At 3 months post‐radiotherapy, the IMRT group had significant and clinically meaningful worsening of BF (−9.3, P <.001), whereas the change in BF score of the PBT cohort was no longer significant or clinically meaningful (−1.2, P =.25). There were no significant or clinically meaningful changes in UO or UI 3 months post‐radiotherapy. Conclusions: PBT had less acute decrement in BF than IMRT following radiotherapy. There was no difference between the two modalities in UO and UI. [ABSTRACT FROM AUTHOR]

We recently characterized S426A/S430A mutant mice expressing a desensitization-resistant form of the CB1 receptor. These mice display an enhanced response to endocannabinoids and ∆9-THC. In this study, S426A/S430A mutants were used as a novel model to test whether ethanol consumption, morphine dependence, and reward for these drugs are potentiated in mice with a “hyper-sensitive” form of CB1. Using an unlimited-access, two-bottle choice, voluntary drinking paradigm, S426A/S430A mutants exhibit modestly increased intake and preference for low (6%) but not higher concentrations of ethanol. S426A/S430A mutants and wild-type mice show similar taste preference for sucrose and quinine, exhibit normal sensitivity to the hypothermic and ataxic effects of ethanol, and have normal blood ethanol concentrations following administration of ethanol. S426A/S430A mutants develop robust conditioned place preference for ethanol (2 g/kg), morphine (10 mg/kg), and cocaine (10 mg/kg), demonstrating that drug reward is not changed in S426A/S430A mutants. Precipitated morphine withdrawal is also unchanged in opioid-dependent S426A/S430A mutant mice. Although ethanol consumption is modestly changed by enhanced CB1 signaling, reward, tolerance, and acute sensitivity to ethanol and morphine are normal in this model. [ABSTRACT FROM AUTHOR]

Purpose: Limited duration cytoreductive neoadjuvant hormonal therapy (NHT) is used prior to definitive radiotherapeutic management of prostate cancer to decrease prostate volume. The purpose of this study is to examine the effect of NHT on prostate volume before permanent prostate brachytherapy (PPB), and determine associated predictive factors. Material and methods: Between June 1998 and April 2012, a total of 1,110 patients underwent PPB and 207 patients underwent NHT. Of these, 189 (91.3%) underwent detailed planimetric transrectal ultrasound before and after NHT prior to PPB. Regression analysis was used to assess predictors of absolute and percentage change in prostate volume after NHT. Results: The median duration of NHT was 4.9 months with inter quartile range (IQR), 4.2-6.6 months. Prostatespecific antigen (PSA) reduced by a median of 97% following NHT. The mean prostate volume before NHT was 62.5 ± 22.1 cm3 (IQR: 46-76 cm3), and after NHT, it was 37.0 ± 14.5 cm3 (IQR: 29-47 cm3). The mean prostate volume reduction was 23.4 cm3 (35.9%). Absolute prostate volume reduction was positively correlated with initial volume and inversely correlated with T-stage, Gleason score, and NCCN risk group. In multivariate regression analyses, initial prostate volume (p < 0.001) remained as a significant predictor of absolute and percent prostate volume reduction. Total androgen suppression was associated with greater percent prostate volume reduction than luteinizing hormone releasing hormone agonist (LHRHa) alone (p = 0.001). Conclusions: Prostate volume decreased by approximately one third after 4.9 months of NHT, with total androgen suppression found to be more efficacious in maximizing cytoreduction than LHRHa alone. Initial prostate volume is the greatest predictor for prostate volume reduction. [ABSTRACT FROM AUTHOR]

Multiple lines of evidence implicate the endocannabinoid signaling system in the modulation of metabolic disease. Genetic or pharmacological inactivation of CB1 in rodents leads to reduced body weight, resistance to diet-induced obesity, decreased intake of highly palatable food, and increased energy expenditure. Cannabinoid agonists stimulate feeding in rodents and increased levels of endocannabinoids can disrupt lipid metabolism. Therefore, the hypothesis that sustained endocannabinoid signaling can lead to obesity and diabetes was examined in this study using S426A/S430A mutant mice expressing a desensitization-resistant CB1 receptor. These mice display exaggerated and prolonged responses to acute administration of phytocannabinoids, synthetic cannabinoids, and endocannabinoids. As a consequence these mice represent a novel model for determining the effect of enhanced endocannabinoid signaling on metabolic disease. S426A/S430A mutants consumed equivalent amounts of both high fat (45%) and low fat (10%) chow control diet compared to wild-type littermate controls. S426A/S430A mutants and wild-type mice fed either high or low fat control diet displayed similar fasting blood glucose levels and normal glucose clearance following a 2 g/kg glucose challenge. Furthermore, S426A/S430A mutants and wild-type mice consumed similar amounts of chow following an overnight fast. While both THC and JZL195 significantly increased food intake two hours after injection, this increase was similar between the S426A/S430A mutant and wildtype control mice Our results indicate that S426A/S430A mutant mice expressing the desensitization-resistant form of CB1 do not exhibit differences in body weight, food intake, glucose homeostasis, or re-feeding following a fast. [ABSTRACT FROM AUTHOR]

Purpose: Effective permanent prostate brachytherapy (PPB) requires precise placement of radioactive seeds in and around the prostate. The impetus for this research is to examine a new ultrasoundbased imaging modality, vibro-acoustography (VA), which may serve to provide a high rate of PPB seed detection while also effecting enhanced prostate imaging. The authors investigate the ability of VA, implemented on a clinical ultrasound (US) scanner and equipped with a quasi-2D (Q2D) array US transducer, to detect and localize PPB seeds in excised prostate specimens. Methods: Nonradioactive brachytherapy seeds were implanted into four excised cadaver prostates. A clinical US scanner equipped with a Q2D array US transducer was customized to acquire both US and C-scan VA images at various depths. The VA images were then used to detect and localize the implanted seeds in prostate tissue. To validate the VA results, computed tomography (CT) images of the same tissue samples were obtained to serve as the reference by which to evaluate the performance of VA in PPB seed detection. Results: The results indicate that VA is capable of accurately identifying the presence and distribution of PPB seeds with a high imaging contrast. Moreover, a large ratio of the PPB seeds implanted into prostate tissue samples could be detected through acquired VA images. Using CT-based seed identification as the standard, VA was capable of detecting 74%-92% of the implanted seeds. Additionally, the angular independency of VA in detecting PPB seeds was demonstrated through a well-controlled phantom experiment. Conclusions: Q2DVA detected a substantial portion of the seeds by using a 2D array US transducer in excised prostate tissue specimens. While VA has inherent advantages associated with conventional US imaging, it has the additional advantage of permitting detection of PPB seeds independent of their orientation. These results suggest the potential of VA as a method for PPB imaging that ultimately may allow US-based real-time intraoperative dosimetry. [ABSTRACT FROM AUTHOR]

For many G-protein-coupled receptors (GPCRs), including cannabinoid receptor 1 (CB1R), desensitization has been proposed as a principal mechanism driving initial tolerance to agonists. GPCR desensitization typically requires phosphorylation by a G-proteincoupled receptor kinase (GRK) and interaction of the phosphorylated receptor with an arrestin. In simple model systems, CB1R is desensitized by GRK phosphorylation at two serine residues (S426 and S430). However, the role of these serine residues in tolerance and dependence for cannabinoids in vivo was unclear. Therefore, we generated mice where S426 and S430 were mutated to nonphosphorylatable alanines (S426A/S430A). S426A/S430A mutant mice were more sensitive to acutely administered delta-9-tetrahydrocannabinol (9-THC), have delayed tolerance to Δ9-THC, and showed increased dependence for Δ9-THC. S426A/S430A mutants also showed increased responses to elevated levels of endogenous cannabinoids. CB1R desensitization in the periaqueductal gray and spinal cord following7dof treatment withΔ9-THC was absent in S426A/S430A mutants.Δ9-THC-induced downregulation of CB1Rin the spinal cord was also absent in S426A/S430A mutants. Cultured autaptic hippocampal neurons from S426A/S430A mice showed enhanced endocannabinoid-mediated depolarization-induced suppression of excitation (DSE) and reduced agonist-mediated desensitization of DSE. These results indicate that S426 and S430 play major roles in the acute response to, tolerance to, and dependence on cannabinoids. Additionally, S426A/S430A mice are a novel model for studying pathophysiological processes thought to involve excessive endocannabinoid signaling such as drug addiction and metabolic disease. These mice also validate the approach of mutating GRK phosphorylation sites involved in desensitization as a general means to confer exaggerated signaling to GPCRs in vivo. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): To report outcomes and toxicity for patients with oligometastatic (<5 lesions) prostate cancer (PCa) treated with stereotactic body radiation therapy (SBRT). Materials/methods: Seventeen men with 21 PCa lesions were treated with SBRT between February 2009 and November 2011. All patients had a detectable prostate-specific antigen (PSA) at the time of SBRT and 11 patients (65%) had hormone-refractory (HR) disease. Treatment sites included bone (n = 19), lymph nodes (n = 1), and liver (n = 1). For patients with bone lesions, the median dose was 20 Gy (range, 8-24 Gy) in a single fraction (range, 1-3). All but two patients received some form of anti-androgen therapy after completing SBRT Results: Local control (LC) was 100%, and the PSA nadir was undetectable in nine patients (53%). The first post-SBRT PSA was lower than pre-treatment levels in 15 patients (88%), and continued to decline or remain undetectable in 12 patients (71%) at a median follow-up of 6 months (range, 2-24 months). Median PSA measurements before SBRT and at last follow-up were 2.1 ng/dl (range, 0.13-36.4) and 0.17 ng/dl (range, <0.1-140), respectively. Six (55%) of the 11 patients with HR PCa achieved either undetectable or declining PSA at a median follow-up of 4.8 months (range, 2.2-6.0 months). Reported toxicities included one case each of grade 2 dyspnea and back pain, there were no cases of grade >3 toxicity following treatment. Conclusion: We report excellent LC with SBRT in oligometastatic PCa. More importantly, over half the patients achieved an undetectable PSA after SBRT. Further follow-up is necessaryto assess the long-term impact of SBRT on LC, toxicity, PSA response, and clinical outcomes. [ABSTRACT FROM AUTHOR]

Purpose/Objective(s): To report outcomes and toxicity for patients with oligometastatic (≤5 lesions) prostate cancer (PCa) treated with stereotactic body radiotherapy (SBRT). Materials/Methods: Seventeen men with 21 PCa lesions were treated with SBRT between February 2009 and November 2011. All patients had a detectable prostate-specific antigen (PSA) at the time of SBRT, and 11 patients (65%) had hormone-refractory (HR) disease. Treatment sites included bone (n=19), lymph nodes (n=1), and liver (n=1). For patients with bone lesions, the median dose was 20 Gy (range, 8-24 Gy) in a single fraction (range, 1-3). All but two patients received some form of anti-androgen therapy after completing SBRT. Results: Local control (LC) was 100%, and the PSA nadir was undetectable in 9 (53%) patients. The first post-SBRT PSA was lower than pre-treatment levels in 15 patients (88%), and continued to decline or remain undetectable in 12 patients (71%) at a median follow-up of 6 months (range, 2-24 months). Median PSA measurements before SBRT and at last follow-up were 2.1 ng/dl (range, 0.13 - 36.4) and 0.17 ng/dl (range, <0.1- 140), respectively. Six (55%) of the 11 patients with HR PCa achieved either undetectable or declining PSA at a median follow-up of 4.8 months (range, 2.2-6.0 months). Reported toxicities included one case each of grade 2 dyspnea and back pain, there were no cases of grade ≥3 toxicity following treatment. Conclusion: We report excellent LC with SBRT in oligometastatic PCa. More importantly, over half the patients achieved an undetectable PSA after SBRT. Further follow-up is necessary to assess the long-term impact of SBRT on local control, toxicity, PSA response, and clinical outcomes. [ABSTRACT FROM AUTHOR]

Gene therapy has held promise to correct various disease processes. Prostate cancer rep-resents the second leading cause of cancer death in American men. A number of clinical trials involving gene therapy for the treatment of prostate cancer have been reported. The ability to efficiently transduce tumors with effective levels of therapeutic genes has been identified as a fundamental barrier to effective cancer gene therapy. The approach utilizing gene therapy in prostate cancer patients at our institution attempts to address this deficiency. The sodium-iodide symporter (NIS) is responsible for the ability of the thyroid gland to transport and concentrate iodide. The characteristics of the NIS gene suggest that it could represent an ideal therapeutic gene for cancer therapy. Published results from Mayo Clinic researchers have indicated several important successes with the use of the NIS gene and prostate gene therapy. Studies have demonstrated that transfer of the human NIS gene into prostate cancer using adenovirus vectors in vitro and in vivo results in efficient uptake of radioactive iodine and significant tumor growth delay with prolongation of survival. Preclinical successes have culminated in the opening of a phase I trial for patients with advanced prostate disease which is currently accruing patients. Further study will reveal the clinical promise of NIS gene therapy in the treatment of prostate as well as other malignancies. [ABSTRACT FROM AUTHOR]

Gene therapy has held promise to correct various disease processes. Prostate cancer represents the second leading cause of cancer death in American men. A number of clinical trials involving gene therapy for the treatment of prostate cancer have been reported. The ability to efficiently transduce tumors with effective levels of therapeutic genes has been identified as a fundamental barrier to effective cancer gene therapy. The approach utilizing gene therapy in prostate cancer patients at our institution attempts to address this deficiency. The sodium-iodide symporter (NIS) is responsible for the ability of the thyroid gland to transport and concentrate iodide. The characteristics of the NIS gene suggest that it could represent an ideal therapeutic gene for cancer therapy. Published results from Mayo Clinic researchers have indicated several important successes with the use of the NIS gene and prostate gene therapy. Studies have demonstrated that transfer of the human NIS gene into prostate cancer using adenovirus vectors in vitro and in vivo results in efficient uptake of radioactive iodine and significant tumor growth delay with prolongation of survival. Preclinical successes have culminated in the opening of a phase I trial for patients with advanced prostate disease which is currently accruing patients. Further study will reveal the clinical promise of NIS gene therapy in the treatment of prostate as well as other malignancies. [ABSTRACT FROM AUTHOR]

Background and Purpose: Numerous studies have shown that N-arachidonoylethanolamine (AEA) can inhibit sperm motility and function but the ability of cannabinoids to inhibit sperm motility is not well understood. We investigated the effects of WIN 55,212-2, a CB(1) cannabinoid receptor agonist, and Δ(9) -tetrahydracannabinol (Δ(9) -THC) on the ATP levels and motility of murine sperm in vitro. In addition, the effects of acute administration of Δ(9) -THC on male fecundity were determined.Experimental Approach: Effects of Δ(9) -THC on basal sperm kinematics were determined using computer-assisted sperm analysis (CASA). Stop-motion imaging was performed to measure sperm beat frequency. The effect of Δ(9) -THC on sperm ATP was determined using a luciferase assay. Male fertility was determined by evaluating the size of litters sired by Δ(9) -THC-treated males. KEY RESULTS Pretreatment of sperm for 15 min with 1 µM Δ(9) -THC reduced their basal motility and attenuated the ability of bicarbonate to stimulate flagellar beat frequency. Treatment with 5 µM WIN 55,212-2 or 10 µM Δ(9) -THC for 30 min reduced sperm ATP levels. In sperm lacking CB(1) receptors this inhibitory effect of WIN 55,212-2 on ATP was attenuated whereas that of Δ(9) -THC persisted. Administration of 50 mg·kg(-1) Δ(9) -THC to male mice just before mating caused a 20% decrease in embryonic litter size.Conclusions and Implications: Δ(9) -THC inhibits both basal and bicarbonate-stimulated sperm motility in vitro and reduces male fertility in vivo. High concentrations of WIN 55,212-2 or Δ(9) -THC inhibit ATP production in sperm; this effect of WIN 55,212-2 is CB(1) receptor-dependent whereas that of Δ(9) -THC is not. LINKED ARTICLES This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7. [ABSTRACT FROM AUTHOR]

BACKGROUND AND PURPOSE Numerous studies have shown that N-arachidonoylethanolamine (AEA) can inhibit sperm motility and function but the ability of cannabinoids to inhibit sperm motility is not well understood. We investigated the effects of WIN 55,212-2, a CB1 cannabinoid receptor agonist, and Δ9-tetrahydracannabinol (Δ9-THC) on the ATP levels and motility of murine sperm in vitro. In addition, the effects of acute administration of Δ9-THC on male fecundity were determined. EXPERIMENTAL APPROACH Effects of Δ9-THC on basal sperm kinematics were determined using computer-assisted sperm analysis (CASA). Stop-motion imaging was performed to measure sperm beat frequency. The effect of Δ9-THC on sperm ATP was determined using a luciferase assay. Male fertility was determined by evaluating the size of litters sired by Δ9-THC-treated males. KEY RESULTS Pretreatment of sperm for 15 min with 1 µM Δ9-THC reduced their basal motility and attenuated the ability of bicarbonate to stimulate flagellar beat frequency. Treatment with 5 µM WIN 55,212-2 or 10 µM Δ9-THC for 30 min reduced sperm ATP levels. In sperm lacking CB1 receptors this inhibitory effect of WIN 55,212-2 on ATP was attenuated whereas that of Δ9-THC persisted. Administration of 50 mg·kg−1Δ9-THC to male mice just before mating caused a 20% decrease in embryonic litter size. CONCLUSIONS AND IMPLICATIONS Δ9-THC inhibits both basal and bicarbonate-stimulated sperm motility in vitro and reduces male fertility in vivo. High concentrations of WIN 55,212-2 or Δ9-THC inhibit ATP production in sperm; this effect of WIN 55,212-2 is CB1 receptor-dependent whereas that of Δ9-THC is not. LINKED ARTICLES This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit . To view Part I of Cannabinoids in Biology and Medicine visit [ABSTRACT FROM AUTHOR]

The objective of this research is to prospectively evaluate the feasibility of vibroacoustography (VA) imaging in monitoring prostate cryotherapy in an ex vivo model. Baseline scanning of an excised human prostate is accomplished by a VA system apparatus in a tank of degassed water. Alcohol and dry ice mixture are used to freeze two prostate tissue samples. The frozen prostates are subsequently placed within the water tank at 27°C and rescanned. VA images were acquired at prescribed time intervals to characterize the acoustic properties of the partially frozen tissue. The frozen prostate tissue appears in the images as hypoemitting signal. Once the tissue thaws, previously frozen regions show coarser texture than prior to freezing. The margin of the frozen tissue is delineated with a well-defined rim. The thawed cryolesions show a different contrast compared with normal unfrozen prostate. In conclusion, this pilot study shows that VA produces clear images of a frozen prostate at different temperature stages. The frozen tissue appears as a uniform region with well-defined borders that are readily identified. These characteristic images should allow safer and more efficient application of prostatic cryosurgery. These results provide substantial motivation to further investigate VA as a potential modality to monitor prostate cryotherapy intraoperatively. [ABSTRACT FROM AUTHOR]

Background: Many men develop a rising PSA after initial therapy for prostate cancer. While some of these men will develop a local or metastatic recurrence that warrants further therapy, others will have no evidence of disease progression. We hypothesized that an expression biomarker panel can predict which men with a rising PSA would benefit from further therapy. Methodology/Principal Findings: A case-control design was used to test the association of gene expression with outcome. Systemic (SYS) progression cases were men post-prostatectomy who developed systemic progression within 5 years after PSA recurrence. PSA progression controls were matched men post-prostatectomy with PSA recurrence but no evidence of clinical progression within 5 years. Using expression arrays optimized for paraffin-embedded tissue RNA, 1021 cancerrelated genes were evaluated-including 570 genes implicated in prostate cancer progression. Genes from 8 previously reported marker panels were included. A systemic progression model containing 17 genes was developed. This model generated an AUC of 0.88 (95% CI: 0.84-0.92). Similar AUCs were generated using 3 previously reported panels. In secondary analyses, the model predicted the endpoints of prostate cancer death (in SYS cases) and systemic progression beyond 5 years (in PSA controls) with hazard ratios 2.5 and 4.7, respectively (log-rank p-values of 0.0007 and 0.0005). Genes mapped to 8q24 were significantly enriched in the model. Conclusions/Significance: Specific gene expression patterns are significantly associated with systemic progression after PSA recurrence. The measurement of gene expression pattern may be useful for determining which men may benefit from additional therapy after PSA recurrence. [ABSTRACT FROM AUTHOR]

Fluoroscopy-based three-dimensional seed localization as a component of intraoperative dosimetry for prostate brachytherapy is an active area of research. A novel adaptive-grouping-based reconstruction approach is developed. This approach can recover overlapped seeds that are not detected from the fluoroscopic images. Two versions of the adaptive-grouping-based reconstruction approach are implemented and compared to an epipolar geometry-based seed reconstruction technique. Simulations based on nine patient datasets are used to validate the algorithms. A total of 2259 reconstructions is performed in which different types of error such as random noise in seed image locations and ambiguities in projection geometry are incorporated. Among those reconstructions, nine of the cases with overlapping seeds and the different types of error are performed. It is demonstrated that the adaptive-grouping-based reconstruction method is more accurate than the epipolar geometry method and allows faster reconstruction. At a random noise level of 0.6 mm, the mean distance error in reconstructed seed locations is approximately 1.0 mm for one of the relevant cases examined in detail. The best adaptive-grouping-based approach successfully recovered overlapped seeds in the majority of simulated cases (89%), with the remainder of cases generating one false positive seed. Phantom validation is also performed, and overlapped seeds are successfully recovered with all 92 seeds correctly localized and reconstructed. The mean distance error between segmented seed images and projected seeds is 0.5 mm in the phantom study. [ABSTRACT FROM AUTHOR]

Objective: To develop and evaluate an integrated approach to intra-operative dosimetry for permanent prostate brachytherapy (PPB) by combining a fluoroscopy-based seed localization routine with a transrectal ultrasound (TRUS)-to-fluoroscopy fusion technique. Materials and Methods: Three-dimensional seed coordinates are reconstructed based on the two-dimensional seed locations identified from three fluoroscopic images acquired at different angles. A seed-based registration approach was examined in both simulation and phantom studies to register the seed locations identified from the fluoroscopic images to the TRUS images. Dose parameters were then evaluated and compared to CT-based dosimetry from a patient dataset. Results: Less than 0.2% error in the D90 value was observed using the TRUS-fluoroscopy image-fusion-based method relative to the CT-based post-implantation dosimetry. In the phantom study, an average distance of 3 mm was observed between the seeds identified from TRUS and the reconstructed seeds at registration. Isodose contours were displayed superimposed on the TRUS images. Conclusions: Promising results were observed in this preliminary study of a TRUS-fluoroscopy fusion-based brachytherapy dosimetry analysis method, suggesting that the method is highly sensitive and calculates clinically relevant dosimetry, including the prostate D90. Further validation of the method is required for eventual clinical application. [ABSTRACT FROM AUTHOR]

The article discusses two different perspectives in the management of extraprostatic tumor extension and/or surgical margin-positive prostate cancer after radical prostatectomy. It discloses the results of several studies which indicate the benefit of adjuvant radiotherapy (RT) in terms of antigen relapse-free survival. It suggests that further study is needed to address the question on the effectiveness of surveillance with timely implementation of salvage RT limited only to those with relapse.

A fluoroscopic to TRUS fusion based approach for intraoperative prostate brachytherapy dosimetry was developed. Seed images were identified from multiple fluoroscopic images and reconstructed to determine the three dimensional distribution of the implanted seeds. Seeds identified from the TRUS images were used as fiducials for the registration between fluoroscopic and TRUS images. Dose analysis was then performed based on the fused images. A phantom study was performed to test this approach and a 3 mm registration error was observed. Radiation isodose contours were generated and superimposed on the TRUS images. [ABSTRACT FROM AUTHOR]

The article focuses on the U.S. Preventive Services Task Force's (USPSTF) recommendation to use the serum prostate-specific antigen (PSA) test to facilitate prostate cancer detection. The USPSTF recommended against routine screening in any man of any age, race, or family history of prostate cancer, saying that some screening and observation trials failed to show a survival benefit.

Plano-concave lenses and concave radiators used in scanning focused ultrasound systems have well-established capabilities for deep and selective tumor hyperthermia. The focal intensity gain, a good predictor of selective heating, is expressed as a function of the treatment depth below a planar beam portal integument, frequency-dependent tissue absorption rate, wavenumber, and aperture angle. From this expression novel and useful relations are derived for the maximum focal gain as a function of system specific maximum aperture angle, optimum frequency, and other parameters. Temperature distributions from in vitro and tissue phantom experiments designed to establish minimum gain criteria for selective heating with 'pivoted' and circular scanned focused beams are presented. Measured intensity fields are compared with numerical models that aim to (1) solve the diffraction pattern of an absorbing spherical lens coupled to a clamped piston radiator, (2) predict the intensity field of a focused beam in an absorbing medium, and (3) account for lens propagation that is not parallel to the beam axis. [Work supported by USPHS Grant No. 31303 and the Lutheran Brotherhood.] [ABSTRACT FROM AUTHOR]

Background: Prostate-specific antigen (PSA) nadir + 2 ng/mL, also known as the Phoenix definition, is the definition most commonly used to establish biochemical failure (BF) after external beam radiotherapy for prostate cancer management. The purpose of this study is to compare BF rates between permanent prostate brachytherapy (PPB) and radical retropubic prostatectomy (RRP) as a function of PSA nadir plus varying values of X and examine the associated implications.Methods and Materials: We retrospectively searched for patients who underwent PPB or RRP at our institution between 1998 and 2004. Only primary patients not receiving androgen-deprivation therapy were included in the study. Three RRP patients were matched to each PPB patient on the basis of prognostic factors. BF rates were estimated for PSA nadirs + different values of X.Results: A total of 1,164 patients were used for analysis: 873 in the RRP group and 291 in the PPB group. Patients were equally matched by clinical stage, biopsy Gleason sum, primary Gleason grade, and pretherapy PSA value. Median follow-up was 3.1 years for RRP patients and 3.6 years in the PPB group (P = .01). Using PSA nadir + 0.1 ng/mL for the definition of BF, the 5-year BF rate was 16.3% for PPB patients and 13.5% for RRP patients (P = .007), whereas at nadir + 2 ng/mL or greater, the BF rates were less than 3% and were indistinguishable between PPB and RRP patients.Conclusions: In a cohort of well-matched patients who had prostatectomy or brachytherapy, we examined BF as a function of nadir + X, where X was treated as a continuous variable. As X increases from 0.1 to 2.0 ng/mL, the BF curves converge, and above 2.0 ng/mL they are essentially indistinguishable. The data presented are of interest as BF definitions continue to evolve. [ABSTRACT FROM AUTHOR]