Seminal Vesicle Research Articles

Two species of Polycelis (Platyhelminthes, Tricladida, Planariidae) newly recorded for the Qinling Mountains and the Loess Plateau in China, with a comparative discussion on their karyotypes

The paper details new geographic records of two species of the genus Polycelis Ehrenberg,1831 (Platyhelminthes, Tricladida, Planariidae) for the Qinling Mountains and the Loess Plateau in China and provides redescriptions of these species based on an integrative taxonomic study involving morphology, karyology, and histology. This new information considerably expands our knowledge on these species, for which until now only limited data was available. The species Polycelis asiatica Selinova, 1985 is characterized by the following features: 63–80 eyes; sperm ducts that exhibit an intrabulbar knee-shaped bend towards the ventral surface before opening separately and symmetrically into the antero-dorsal portion of a large seminal vesicle; the latter is ventrally displaced, thus creating a narrow ventral lip on the penis papilla; dorsal wall of the seminal vesicle is provided with several well-developed folds; more or less bulbous penis papilla protrudes from the dorsal wall of the male atrium and is provided with a slender and flexible tip; chromosome complement diploid with 30 metacentric chromosomes, 8 submetacentric chromosomes, and 2 subtelocentric chromosomes. The species Polycelis eudendrocoeloides (Zabusova, 1929) is characterized by: 49–80 eyes; highly reduced and blunt penis, provided with a kind of flagellum that projects into the seminal vesicle; a relatively thick coat of circular and longitudinal muscles around the entire male atrium; generally, a very large intrabulbar seminal vesicle, extending from near the ventral body surface to occupy the major part of both the penis bulb and the dorso-ventral space of the body; diploid chromosome complement consisting of 36 metacentric chromosomes.

Peripubertal exposure to oxyfluorfen, a diphenyl herbicide, delays pubertal development in the male rat by antagonizing androgen receptor activity.

We recently identified the herbicide oxyfluorfen as an inhibitor of iodide uptake by the sodium iodide symporter (NIS), a key step in thyroid hormone synthesis, using in vitro assays. We also observed a suppression of serum T4 and T3 in juvenile rats exposed orally to oxyfluorfen for 4-8 days. The purpose of the present study was to further evaluate effects of an extended 31-day oral exposure using a male pubertal rat study (15 to 500 mg/kg). Oxyfluorfen delayed puberty at all doses (1.3 -3.5 days) suppressing ventral prostate at 62.5 mg/kg and above and seminal vesicle weights at 31.25 mg/kg and above with no effect on testosterone or luteinizing hormone. Serum T4 and T3 were suppressed by all doses up to 80%, with a linear increase in serum TSH. Based on delayed puberty without changes in testosterone, we hypothesized that oxyfluorfen interferes with androgen receptor (AR) function. Results from our Hershberger study, with oxyfluorfen (62.5 and 125 mg/kg) co-treated with testosterone proprionate (TP , 1 mg/kg) for 10 days showed 3 of 5 of the androgenic tissue weights were suppressed compared to TP alone indicating AR antagonism. We next confirmed this effect in an in vitro AR transcriptional activation reporter assay (0-20 μM) with 125 pM 5αDH-11-ketotestosterone and found concentration-dependent inhibition of AR luminescence activity (EC50 1.75 µM) without cytotoxicity. Here, we confirmed the endocrine disrupting effects of oxyfluorfen using both in vitro and in vivo evaluations of the thyroid hormone and AR pathways. This abstract doesn't necessarily reflect U.S. EPA policy.

Distribution of progesterone receptors and the membrane component of progesterone receptor in various organs and tissues of male and female rats

Progesterone regulates reproductive processes and affects many functions of various non-reproductive organs. Its effects in mammals and humans are mediated by nuclear (nPRs) and membrane progesterone receptors (mPRs). The action of progesterone through different types of receptors may differ significantly and has tissue specific features. The expression of known types and subtypes of progesterone receptors in the tissues of male and female rats has been studied fragmentarily. The purpose of our work was to study the expression of five mPRs genes, as well as the nPRs gene and the membrane component of the progesterone receptor PGRMC I in the reproductive organs and in 17 non-reproductive tissues of male and female rats using reverse transcription followed by real-time PCR. In this study, it was shown that a high level of nPRs gene expression in rats is found not only in reproductive organs of females (uterus, ovary, mammary glands), but also in seminal vesicles of males, in the brain and trachea of both sexes, in blood vessels, and in the pancreas of females. The highest level of expression of mPRs genes of all subtypes was found in the testes, while expression of the gene encoding nPRs was practically undetectable in them. Expression of genes encoding mPRs was also detected in the liver and spleen of male and female rats, while expression of the gene encoding nPRs was at background levels. Virtually no expression of nPRs, mPRs, and membrane component of progesterone receptor (PGRMC I) genes was detected in muscle, and its level was very low in the heart in animals of both sexes. We found sex-specific differentiation of nuclear and membrane receptor mRNA levels in rats in non-reproductive tissues, characterized by a predominance of nPRs transcripts and three subtypes of mPRs (α, β, δ) in females and two subtypes of mPRs (γ, ε) in males. Data on the presence of progesterone receptors in tissues not involved in reproduction confirm the effect of progesterone on these organs. High levels of mRNA for various progesterone receptors in the tissues of male rats, such as the pancreas, lungs, kidney, and trachea, indicate an important physiological role of progestins not only in females, but also in males, which is still poorly understood. The work also discusses the known functions of progesterone receptors in the tissues studied.

Simulation of focal boosting in online adaptive MRI-guided SBRT for patients with locally advanced prostate cancer with seminal vesicle involvement

Simulation of focal boosting in online adaptive MRI-guided SBRT for patients with locally advanced prostate cancer with seminal vesicle involvement

The evolutionarily conserved PhLP3 is essential for sperm development in Drosophila melanogaster.

Phosducin-like proteins (PhLP) are thioredoxin domain-containing proteins that are highly conserved across unicellular and multicellular organisms. PhLP family proteins are hypothesized to function as co-chaperones in the folding of cytoskeletal proteins. Here, we present the initial molecular, biochemical, and functional characterization of CG4511 as Drosophila melanogaster PhLP3. We cloned the gene into a bacterial expression vector and produced enzymatically active recombinant PhLP3, which showed similar kinetics to previously characterized orthologues. A fly strain homozygous for a P-element insertion in the 5' UTR of the PhLP3 gene exhibited significant downregulation of PhLP3 expression. We found these male flies to be sterile. Microscopic analysis revealed altered testes morphology and impairment of spermiogenesis, leading to a lack of mature sperm. Among the most significant observations was the lack of actin cones during sperm maturation. Excision of the P-element insertion in PhLP3 restored male fertility, spermiogenesis, and seminal vesicle size. Given the high level of conservation of PhLP3, our data suggests PhLP3 may be an important regulator of sperm development across species.

Primary seminal vesicle diffuse large B-cell lymphoma: a case report and review of the literatures

Primary seminal vesicle lymphoma is a remarkably rare condition, predominantly manifesting as diffuse large B-cell lymphoma. Due to its rarity and nonspecific clinical presentations, it is often misdiagnosed or overlooked. Here, we report a case of a 68-year-old male diagnosed with primary seminal vesicle lymphoma, coinciding with prostate cancer. The diagnosis followed initial findings of elevated prostate-specific antigen levels and abnormal magnetic resonance imaging of the prostate and left seminal vesicle. Suspicion of prostate cancer led to a radical resection of both the prostate and seminal vesicle. Subsequent pathological examination and next-generation sequencing post-surgery confirmed the diagnosis of primary seminal vesicle diffuse large B-cell lymphoma, characterized by CD79B mutation type (MCD type). The patient was treated with six cycles of the R-CHOP regimen (rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone), achieving complete metabolic remission as confirmed by positron emission tomography-computed tomography. Fifteen months post-treatment, the patient’s condition remains favorable. Through our literature review of additional six cases of primary seminal vesicle lymphoma, we aim to elucidate the typical clinical presentations, imaging features, pathological characteristics, genetic mutations, and therapeutic strategies, aiming to contribute to better detection and management of this rare malignancy. This case underscores the diagnostic challenges and emphasizes the necessity for heightened clinical suspicion and definitive pathological examination in the management of primary seminal vesicle lymphoma.

Safety and Efficacy of Neoadjuvant Docetaxel and Radiotherapy in Localized High-Risk Prostate Cancer: Results From a Prospective Pilot Study.

Approximately 15% of patients with localized prostate cancer are at high risk for disease recurrence. Many clinical trials have evaluated the impact of neoadjuvant therapy before radical prostatectomy with mixed results (NCT00321698). This phase I/II clinical trial evaluated the tolerability and preliminary efficacy of neoadjuvant radiation therapy and docetaxel before prostatectomy in 25 men with high-risk prostate cancer. The treatment regimen included 45Gy radiotherapy in 25 fractions to the prostate and seminal vesicles over 5 weeks, along with weekly dose-escalated docetaxel up to 30mg/m², followed by prostatectomy and bilateral lymph node dissection. The primary endpoint was the rate of pathologic complete response (pCR). Secondary endpoints included adverse events, symptom and quality of life measures, and prostate-specific antigen metrics. All 25 patients completed the planned treatment. The primary endpoint of pCR was not achieved. Lymphopenia was the most common grade 3 or higher toxicity, with no grade 3 or higher genitourinary or gastrointestinal toxicities observed. With a median follow-up of 11.6 years, the 10-year biochemical recurrence-free survival was 60%, and distant metastasis-free survival was 80%. Prostate cancer-specific survival and overall survival at 10 years were 84% and 60%, respectively. Although pCR was not met, the treatment demonstrated a modest toxicity profile and reasonable long-term outcomes, suggesting feasibility and safety. Further studies are needed to optimize endpoints and assess the efficacy of neoadjuvant treatments compared with standard approaches in high-risk prostate cancer patients.

Radiographic and ultrasonographic findings of seminal vesiculitis with nonmineral stones in a guinea pig: Case report.

This case report refers to a 1-year-old Guinea pig showing signs of anorexia and antipain posture. On abdominal radiography, five rounded mineral opaque structures were evident in the mid-caudal abdomen. On ultrasound, a right seminal vesicle with a reduction in diameter was observed, containing less echogenic material than the contralateral one, with five oval structures with a hyperechogenic contour and a central hypoechogenic area, forming acoustic shadowing. The left seminal vesicle presented with the usual characteristics. After bilateral vesiculectomy, the patient recovered well, with no further symptoms. The histopathological result was a suppurative/abscessive inflammatory process with an accumulation of proteinaceous material.

Identifying Prostatic Utricle Translucent Membrane in Hematospermia Patients Using a Novel Nomogram.

Aims/Background Hematospermia, characterized by blood in the ejaculate, is a common and distressing condition in urology. Identifying the underlying causes, including translucent membranes in the prostatic utricle, is crucial for effective management. Despite advancements in diagnostic techniques, reliable predictive tools are needed to enhance preoperative planning and patient outcomes. This study aimed to develop a novel nomogram to predict the presence of translucent membranes in the prostatic utricle of hematospermia patients. Methods In total, 284 patients were selected from The Second People's Hospital of Hefei database based on inclusion and exclusion criteria. The cohort was divided into a training set (198 patients) and a validation set (86 patients). To identify risk factors associated with the prostatic utricle translucent membrane, multivariable logistic regression analysis was employed. The identified risk factors were then used to construct a predictive nomogram model. The performance of the nomogram was evaluated using several statistical tools: receiver operating characteristic (ROC) curves to assess discriminative ability, calibration curves to evaluate prediction accuracy, and decision curve analysis (DCA) to determine clinical utility. Results The findings revealed that age, duration of disease, history of seminal vesiculitis, and seminal vesicle dimensions (width, length, and thickness) were independent risk factors for the presence of a prostatic utricle translucent membrane in patients with hematospermia. Using these variables, a nomogram was developed. The nomogram demonstrated strong predictive capability, as evidenced by its performance in ROC and calibration curve analyses. Furthermore, the DCA indicated that the nomogram offered significant clinical net benefits in predicting the presence of a translucent membrane. Conclusion Clinical use of the developed nomogram can assist clinicians in identifying patients with hematospermia who have translucent membrane in the prostatic utricle and in developing individualized treatment.

Perioperative, functional, and oncological outcomes of Da Vinci vs. Hugo RAS for robot‑assisted radical prostatectomy: evidence based on controlled studies.

A comparison was conducted between robot-assisted radical prostatectomy (RARP) performed using the Hugo RAS System and the Da Vinci System. We conducted an extensive search of online databases through September 2024. The data from eligible studies were pooled and analyzed with Review Manager 5.4, employing a random effects model. Weighted mean difference (WMD) and odds ratios (OR) with 95% confidence intervals (CI) were used to analyze continuous and categorical variables. A total of eight original studies, involving 1155 patients (HUGO-RARP: 468 vs. da Vinci-RARP: 687), were included. Compared with da Vinci-RARP, HUGO-RARP had a longer docking time (WMD: 6.2min; 95% CI 4.25-8.14; p < 0.0001), while no significant differences were observed in total operative time, console time, bladder neck dissection time, seminal vesicle dissection time, vesicourethral anastomosis time, or pelvic lymph node dissection time between two systems. There were no significant differences in hospital stay, estimated blood loss, catheter duration, or complication rates. Likewise, oncological and functional outcomes were similar between the two systems. While these results suggest that the Hugo RAS system performs as well as the Da Vinci system in RARP, more randomized controlled studies are needed to further evaluate prognostic outcomes.

Accuracy of MRI in detecting seminal vesicle invasion in prostate cancer: a systematic review and meta-analysis.

To determine the diagnostic test accuracy of multiparametric magnetic resonance imaging (mpMRI) in detecting seminal vesicle invasion (SVI). The Medical Literature Analysis and Retrieval System Online (MEDLINE), PubMed, the Excerpta Medica dataBASE (EMBASE) and Cochrane databases were search up to May 2023. We included studies that investigated the accuracy of mpMRI in detecting SVI when compared to radical prostatectomy specimens as the reference standard. Data extraction was performed by two independent reviewers to construct 2 × 2 tables, as well as patient and study characteristics. The methodological quality of the included studies was assessed with the Quality of Assessment of Diagnostic Accuracy Studies-2 tool. Sensitivity and specificity were pooled and presented graphically with summary receiver operator characteristic (SROC) plots. A total of 27 articles with 4862 patients were included for analysis. The summary sensitivity and specificity were 0.57 (95% confidence interval [CI] 0.45-0.68) and 0.95 (95% CI 0.92-0.99), respectively. Meta-regression indicated that there was no evidence that coil strength (P = 0.079), coil type (P = 0.589), year of publication (P = 0.503) or use of the Prostate Imaging-Reporting and Data System (P = 0.873) significantly influenced these results. The summary diagnostic odds ratio was 28.3 (95% CI 15.0-48.8) and the area under the curve for the SROC curve was 0.87. The I2 statistic was a modest 11.9%. In general, methodological quality was good. The use of mpMRI in detecting SVI has excellent specificity but poor sensitivity. Both endorectal coils and magnetic field strength do not significantly impact the accuracy of MRI. These findings suggest that mpMRI cannot reliably rule out SVI in patients with prostate cancer.

Impact of Cyclophosphamide on Testis and Sexual Glands of Adult Albino Rats and Probable Recovery After Drug Withdrawal: A Histological and Immunohistochemical study

Background: Cyclophosphamide is a chemotherapy and an immune-suppressive drug which is used for treatment of malignant and immune –related disease. The current work was conducted to evaluate the histological structure of the male gonad and sexual glands during treatment and after discontinuation of cyclophosphamide. Material and Methods: Thirty male albino- rats were classified into three groups. The first one was treated by normal saline, the second and third groups received cyclophosphamide 150 mg/kg intra peritoneal every two days for one week. The third group regarded as recovery group and divided into two subgroups with one- or two-months’ recovery period. At the accomplishment of the work, blood was drowning for hormonal analysis (testosterone) then the animals were sacrificed. The testis, prostate and seminal vesicle were removed and prepare for histological and immunohistochemical staining. Results: The cyclophosphamide treated group (GII) showed reduction of serum testosterone level, the testicular and sexual glands sections revealed atrophic and degenerative changes of their lining epithelium with reduction of their function and changes of their Ki67 expression which indicate abnormal proliferative pattern of the cells. However, the histopathological changes of treated group showed no improvement after one or even two months of drug withdrawal. Conclusion: The present study pointed out the risk of infertility and gonadal toxicity during cyclophosphamide treatment which may be permanent even after termination of the treatment.

Adaptive divergence in reproductive seasonality and underlying physiological features fit Rattus norvegicus to live as opportunistic breeders.

How organisms respond to complex environments is one of the unsolved problems in ecology. Life history patterns of a species provide essential information on how different populations may respond and adapt to environmental changes. Compared to typical seasonal breeders, which have limited distributions, the worldwide distribution of brown rats (Rattus norvegicus) across highly complex and divergent habitats suggests they exhibit exceptional adaptiveness. However, the difference in physiological mechanisms by which brown rats respond and adapt to markedly different environments is seldom investigated. Here, we reveal a significant divergence in reproductive seasonality and environmental responses between two brown rat subspecies: one subspecies, R. n. caraco, lives in the temperate zone, and another subspecies, R. n. norvegicus, lives in the subtropical region. Although R. n. caraco displayed a significantly higher reproductive seasonality than R. n. norvegicus, both subspecies adapted to sub-optimal breeding conditions mainly by regulating the seminal vesicle rather than testis development. Especially in responding to severe winter conditions in high-latitude regions, bodyweight-dependent recovery of testicular development in adults enables R. n. caraco to initiate reproduction more rapidly when conditions are suited. These findings elucidate a regulatory process of how brown rats live as opportunistic breeders by benefiting from enhanced semen production.

Dietary supplementation with rosemary essential oil improves genital characteristics, semen parameters and testosterone concentration in Barki rams

BackgroundMale reproductive performance is an essential part of sheep production; therefore, the use of natural antioxidants to improve sperm quality and maintain reproductive performance in males is very important. Hence, oral administration of rosemary essential oil (REO) was investigated to improve the fertility rate, including the ultrasonographic testes, epididymal tail and genital glands, as well as semen parameters and testosterone concentration. Sixty animals were splitted into two groups, each with 30 rams; the rosemary group (C + REO) received 2 mg/kg/bw and the control group (C-REO). Ultrasound images and blood samples were collected at 15, 30 and 45 days of the REO treatment.ResultsThe testis and epididymal tail ultrasonographic assessments demonstrated a significant enhancement in the C + REO group compared to the C-REO group. However, the rams in the C + REO group showed significant improvements in the pampini-form plexus, seminal vesicle, Cowper's and prostate genital glands compared to the C-REO group. The data showed that the sperm cell concentration (× 109/ml) and individual motility (%) were significantly improved in the C + REO group. Furthermore, ejaculate volume (ml) in the C + REO group was significantly higher than that in the C-REO group. While the animals treated with REO did not improve live spermatozoa (%), it reduced the abnormalities of spermatozoa (%) compared to the C-REO group. Also, the C + REO group significantly increased the testosterone concentration more than the C-REO group.ConclusionIt can be concluded that supplementation with 2 mg/kg/bw REO improves genital characteristics, semen parameters and testosterone concentration in Barki rams.

Rare Seminal Vesicle Cystadenoma: Case Report and Literature Review

Abstract Introduction/Objective Primary neoplasms of seminal vesicles (SV) are rare, with the majority being metastatic tumors, often from prostatic carcinoma. SV cystadenoma is an exceedingly rare benign epithelial tumor that arises from the remnants of the Mullerian duct. The tumor formed of cysts of variable sizes lined by bland cuboidal epithelium. Herein we present a case of SV cystadenoma in a 38-year-old male, underscoring its rarity and risk of progression to higher grades, as outlined in literature review. Methods/Case Report A 38-year-old male with a history of left atrophic kidney and intermittent pelvic pain due to recurrent obstruction of the SV. Pelvic Magnetic Resonance Imaging revealed a 5.3 cm benign unilocular cyst within the SV, along the posterior aspect of the urinary bladder. The patient underwent successful laparoscopic excision of the left SV. Gross examination of the excised SV demonstrated a 3.5X 2.7X 1.5 cm cyst within the SV. Microscopic examination displayed a benign cyst lined by single to multiple layers of cuboidal epithelium, surrounded by unremarkable SV stroma. The epithelial lining cells exhibited round nuclei with inconspicuous nucleoli, lacking dysplasia. Immunohistochemistry revealed positive staining for cytokeratin 7 and PAX 8 in the epithelial cells, whereas prostatic specific antigen staining was negative. Results (if a Case Study enter NA) NA Conclusion Cystadenoma and mixed epithelial stromal tumors of the SV (MEST) are rare entities, with approximately 30 reported cases. This case demonstrates classic histologic features consistent with low-grade MEST, as per recently proposed grading criteria. Notably, a recent case report has suggested a potential for malignant transformation to high-grade dysplasia and adenocarcinoma in SV cystadenoma, as evidenced by focal epithelial dysplasia.

Straightforward, Highly Useful, Innovative and Cost-Effective Method with Potential to Improve Personalized Diagnosis: Sectioning of Prostatectomy Specimen with a Single Blade

Abstract Introduction/Objective There is potential for devices with an adjustable base and a single blade to precisely cut parallel slices of a prostatectomy specimen at a set preferred thickness to improve pathology practice by standardizing the tissue for histological review, allowing for precise punch biopsies of the slices for molecular diagnostics for biobanking and personalized therapy. The current standard method of sectioning the prostate involves serially sectioning the prostatectomy specimen by hand with a sharp long knife, leading to uneven sections. Methods/Case Report A device with an adjustable base was developed at a regional Veteran Affairs Medical Center (VAMC) that consists of two sets of multiple, vertically arranged parallel and flat bars measuring 10 cm in height, 1.5 cm in width and 0.3 cm in thickness spaced 0.4 cm from each other, resembling a comb with flat teeth. After inking, orientation, and removal of the seminal vesicles and apex and base margins, the prostatectomy specimen is immobilized between the two combs and sliced in parallel from apex to base to produce parallel consistent prostate slices. The ability to obtain punch biopsies from precise areas of the prostate was reviewed. Results (if a Case Study enter NA) The device results in uniform 4 mm thick oriented smooth specimen slices of good quality with minimal distortion. The device allows for the obtaining of punch biopsies taken at precise locations of the prostate corresponding to specific imaging locations (highly useful for biobanking or obtaining diagnostic tissue for molecular diagnostics for personalized therapy). The adjustable nature of the device and single blade gives the device flexibility in the specimen. Conclusion This device with an adjustable base and single blade allows for safe and precise parallel slicing. This is highly useful obtaining diagnostic standardized tissue, for obtaining biobank specimens and for obtaining material of precise location for molecular studies to guide the personalized therapy of tumors.

CT and MRI radiographic characteristics of seminal vesicle cysts

PurposeSeminal vesicle cysts are relatively uncommon benign lesions. Early and accurate diagnosis is crucial for guiding appropriate management strategies. The purpose of this study was to investigate the radiographic characteristics of seminal vesicle cysts in order to enhance the diagnostic proficiency of radiologists. MethodsWe conduct a comprehensive descriptive analysis of the CT and MRI findings pertaining to 15 patients with seminal vesicle cyst, complemented by a brief literature review. ResultThe mean age of 15 patients with seminal vesicle cyst was 57.53 ± 17.0 years. Among these patients, 53.33% (8/15) were incidentally detected, while 40% (6/15) presented with symptoms of abdominal or pelvic pain. One patient exhibited hematospermia. In 86.67% (13/15) of cases, the cysts were unilateral, while the remaining 13.33% (2/15) were bilateral. Radiological assessment comprised CT scans for 7 patients, MRI scans for 12 patients, and a combination of both modalities for 4 patients. Imaging characteristics revealed 11 cases of unilocular cysts and 4 cases of multilocular cysts, with the largest measuring approximately 16.0 × 9.8 cm. CT imaging distinctly demonstrated punctate or nodular calcification along the cyst wall in 3 cases. MRI, on the other hand, facilitated the visualization of cystic contents, including mucinous protein in 9 cases and hemorrhagic components in 2 cases. ConclusionThe radiographic manifestations of seminal vesicle cysts exhibit distinct characteristics, CT and MRI imaging modalities are instrumental in facilitating their accurate diagnosis.

Machine learning and explainable artificial intelligence to predict pathologic stage in men with localized prostate cancer.

Though several nomograms exist, machine learning (ML) approaches might improve prediction of pathologic stage in patients with prostate cancer. To develop ML models to predict pathologic stage that outperform existing nomograms that use readily available clinicopathologic variables. Patients with prostate adenocarcinoma who underwent surgery were identified in the National Cancer Database. Seven ML models were trained to predict organ-confined (OC) disease, extracapsular extension, seminal vesicle invasion (SVI), and lymph node involvement (LNI). Model performance was measured using area under the curve (AUC) on a holdout testing data set. Clinical utility was evaluated using decision curve analysis (DCA). Performance metrics were confirmed on an external validation data set. The ML-based extreme gradient boosted trees model achieved the best performance with an AUC of 0.744, 0.749, 0.816, 0.811 for the OC, ECE, SVI, and LNI models, respectively. The MSK nomograms achieved an AUC of 0.708, 0.742, 0.806, 0.802 for the OC, ECE, SVI, and LNI models, respectively. These models also performed the best on DCA. Findings were consistent on both a holdout internal validation data set as well as an external validation data set. Our ML models better predicted pathologic stage relative to existing nomograms at predicting pathologic stage. Accurate prediction of pathologic stage can help oncologists and patients determine optimal definitive treatment options for patients with prostate cancer.

Interleukin-1 Beta (IL1B) and Nerve Growth Factor (NGF): Key Players in Rabbit Reproductive Regulation.

Several seminal plasma components, besides NGF, are implicated as ovulation-inducing factors in mammals. This study investigated the IL1B and its receptor IL1R1 in the testis (T), male accessory glands, prostate (P) and seminal vesicles (SV), and uterus (U) of adult rabbits using immunohistochemistry (IHC) and quantitative reverse transcription PCR (RT-qPCR). We also assessed the presence of IL1B in seminal plasma through Western blotting (WB) and examined the interaction between IL1B and NGF in vitro by measuring their production with enzyme-linked immunosorbent assay (ELISA) in the presence of NGF and IL1B alone or with their respective receptor antagonists. IHC revealed IL1B system expression in all reproductive organs studied, with IL1B and IL1R1 localized to the germinative epithelium of the T and the epithelial cells of the accessory glands and U. IL1B gene transcript levels were significantly higher (p < 0.01) in the P and SV compared to the T, while IL1R1 levels were significantly higher (p < 0.001) in the P compared to the other tissues, while IL1R1 levels were three times higher (p < 0.001) in the P. WB confirmed the presence of IL1B in seminal plasma with a 30-35 kDa band. The in vitro study demonstrated that IL1B increased (p < 0.05) basal NGF production in the U, whereas NGF had no effect on IL1B production. These findings provide evidence of the expression of the IL1B/IL1R1 system in both male and female rabbit reproductive tracts and suggest that IL1B in seminal plasma may influence uterine endocrine activity. The results propose a potential role for IL1B in ovulation, in conjunction with NGF, supporting that ovulation may involve inflammatory-like processes.

Neurogenic-derived 6-nitrodopamine is the most potent endogenous modulator of the mouse urinary bladder relaxation

6-Nitrodopamine (6-ND) modulates vas deferens, seminal vesicles, and corpus cavernosum contractility; however, its role on the lower urinary tract organs has not been evaluated. Investigations of isolated urinary bladders from wild-type (WT) mice revealed 6-ND release was comparable to that of dopamine and adrenaline, whereas noradrenaline was hardly detected, as assessed by liquid chromatography coupled to tandem mass spectrometry. In vitro, 6-ND induced concentration-dependent relaxations in carbachol pre-contracted bladders with high potency (pEC50: 8.04 ± 0.86), independently of eNOS/sGC activity. Co-incubation of 6-ND (1–10 μM) antagonizes the contractile effects of acetylcholine (p < 0.05). Experiments using nitric oxide synthase (NOS) knockout mice demonstrated that 6-ND release from isolated urinary bladder was significantly reduced by neuronal NOS (nNOS−/−) deletion and abolished by triple NOSs deletion (n/i/eNOS−/−), while no significant changes were observed in endothelial (eNOS−/−) or inducible (iNOS−/−) knockout mice. Incubation with tetrodotoxin resulted in a significant decrease in 6-ND release in bladders obtained from WT, but not in nNOS−/− mice. The bladders from nNOS−/− and n/i/eNOS−/− mice exhibited significantly higher contractile responses to electric field stimulation (EFS), compared to eNOS−/−, iNOS−/−, or WT bladders. The hyperreactivity observed in triple NOS knockouts was reversed by the incubation with bladder mucosal layer obtained from a donor WT mice, but not with the muscular layer. These findings clearly demonstrate 6-ND is the most potent endogenous relaxing agent of urinary bladder, and inhibition of its release is associated with bladder hyperreactivity.