Prevention of urethral fibrosis induced by transforming growth factor beta 1 using selective Wnt/ß-catenin signaling inhibitors in a rat model.

OBJECTIVES: To determine the anti-fibrotic effects of Wnt/ß-catenin signaling inhibitors on urethral stricture. METHODS: Human fibroblasts were exposed to transforming growth factor beta 1 combined with various concentrations of Wnt/ß-catenin inhibitors (ICG-001, IWR-1, and PRI-724), and cell proliferation and migration were evaluated. Urethral fibrosis was induced in male Sprague-Dawley rats by urethral injection of transforming growth factor beta 1 and co-treatement with inhibitors. Urethral tissues were harvested 2 weeks after the injection. The messenger ribonucleic acid and protein expression was examined for fibrosis markers Axin-1, collagen type 1, alpha smooth muscle actin, and ß-catenin. Histological analysis of fibrosis and collagen deposition was also performed. RESULTS: Cell migration was ameliorated by ICG-001 and PRI-724. Protein and messenger ribonucleic acid expression of collagen type 1 and alpha smooth muscle actin in transforming growth factor beta 1-treated fibroblasts decreased in a concentration-dependent manner with the ICG-001 and PRI-724 treatments (P < 0.05). However, there were no significant changes with the IWR-1 treatment. Collagen type I and alpha smooth muscle actin messenger ribonucleic acid and protein expression were both significantly increased in the urethral tissues of rats with transforming growth factor beta 1-induced urethral fibrosis. Rats co-treated with ICG-001 or PRI-724 showed relatively mild fibrosis and significantly reduced collagen type I and alpha smooth muscle actin messenger ribonucleic acid and protein expression (P < 0.05). CONCLUSIONS: ICG-001 and PRI-724 significantly ameliorated urethral fibrosis induced by transforming growth factor beta 1 in rats. These results suggest that ICG-001 and PRI-724 can be developed as therapeutics for treating urethral stricture.

Down-Regulation of Neogenin Decreases Proliferation and Differentiation of Spermatogonia during the Early Phase of Spermatogenesis.

Non-obstructive azoospermia is a major clinical issue associated with male infertility that remains to be addressed. Although neogenin is reportedly abundantly expressed in the testis, its role in mammalian spermatogenesis is unknown. We systematically investigated the role of neogenin during spermatogenesis by performing loss-of-function studies. Testis-specific neogenin conditional knock-out (cKO) mice were generated using CRISPR/Cas9 and neogenin-targeting guide RNAs. We analyzed the expression profiles of germ cell factors by RT-PCR and Western blotting. Neogenin localized mainly to spermatogonia in seminiferous tubules of mouse testes. RT-PCR and Western blot analyses further demonstrated that neogenin expression varied during spermatogenesis and was dramatically increased at postnatal day 12-25 during the pubertal stage. In neogenin-cKO mouse testes, the ratio of primary and secondary spermatocytes was significantly decreased compared with the control, while the number of apoptotic testicular cells was significantly increased. Taken together, these results suggest that neogenin plays a pivotal role in the maintenance and proliferation of spermatogonia during the early stage of spermatogenesis in mice.

Credé maneuver to adjust tape tension during trans-obturator tape mid-urethral sling in mixed urinary incontinence.

INTRODUCTION AND HYPOTHESIS: To evaluate the efficacy of intraoperative extrinsic manual bladder compression (Credé maneuver) for trans-obturator tape adjustment during mid-urethral sling surgery in women with stress urinary incontinence and those with mixed urinary incontinence. METHODS: The study included 148 randomly selected women who underwent mid-urethral sling surgery with trans-obturator tape for stress urinary incontinence between January 2016 and May 2017. Subgroup analysis of 66 women with mixed urinary incontinence included 43 patients from the Credé maneuver group and 23 from the non-Credé maneuver group. In the Credé maneuver group, the pattern of urine leakage was determined during the Credé maneuver, and tape tension was adjusted according to the pattern. RESULTS: The cure rate was 86.6% and improved rate was 11.9% in the Credé maneuver patients. The cure rate was 50.6% and improved rate was 38.3% in the non-Credé maneuver patients. The success rate was significantly higher in the Credé than in the non-Credé maneuver group (p = 0.023). In subgroup analysis of patients with mixed urinary incontinence, the cure rate was 81.4% and improved rate was 16.3% in the Credé maneuver group. The cure rate was 43.5% and improved rate was 47.8% in the non-Credé maneuver group. The cure rate was significantly higher in the Credé maneuver group (p = 0.007). CONCLUSIONS: Intraoperative trans-obturator tape adjustment using the Credé maneuver to identify the leaking pattern significantly improved the success rate in women with mixed urinary incontinence, and Credé maneuver-directed adjustment significantly improved the cure rate.

External validation of the post-varicocele repair semen analysis nomogram to predict total motile sperm count: A multicenter study.

Total motile sperm count is an important parameter for predicting the probability of natural pregnancy. We have externally validated the Samplaski's post-varicocele repair semen analysis nomogram to confirm the predictive accuracy of total motile sperm count. A total of 300 patients who had undergone varicocelectomy between July 2016 and July 2019 from 4 treatment centres were included in this validation cohort study. The predictive performance of the externally validated nomogram was revealed by applying the Pearson correlation coefficient (R = 0.328; 95% confidence interval (CI) 0.220-0.435; p < .001). Compared to Samplaski's nomogram result (R = 0.581; 95% CI 0.186-0.729), our study also revealed a statistically significant rate. However, it had a relatively lower correlation coefficient rate. Notably, the predicted total motile sperm count was lower than the observed post-varicocelectomy total motile sperm count. The calibration plot revealed that the discrepancy between the predicted and observed total motile sperm count was plausible. However, it had low explanatory power in this nomogram model. This validation study demonstrates that the post-varicocele repair Samplaski's nomogram predicts a relatively lower total motile sperm count than the observed count.

Metabolites Produced by the Oral Commensal Bacterium Corynebacterium durum Extend the Lifespan of Caenorhabditis elegans via SIR-2.1 Overexpression.

Human microbiota is heavily involved in host health, including the aging process. Based on the hypothesis that the human microbiota manipulates host aging via the production of chemical messengers, lifespan-extending activities of the metabolites produced by the oral commensal bacterium Corynebacterium durum and derivatives thereof were evaluated using the model organism Caenorhabditis elegans. Chemical investigation of the acetone extract of a C. durum culture led to the identification of monoamines and N-acetyl monoamines as major metabolites. Phenethylamine and N-acetylphenethylamine induced a potent and dose-dependent increase of the C. elegans lifespan, up to 21.6% and 19.9%, respectively. A mechanistic study revealed that the induction of SIR-2.1, a highly conserved protein associated with the regulation of lifespan, was responsible for the observed increased longevity.

Eating Habits and Food Additive Intakes Are Associated with Emotional States Based on EEG and HRV in Healthy Korean Children and Adolescents.

PURPOSE: Recent study suggests that psychological issues and eating habits are closely related. In this study, we aimed to find the association between eating habits and intakes of artificial sweeteners with emotional states of schoolchildren using quantitatively analyzing objective biosignals. METHODS: The study was conducted at the National Standard Reference Data Center for Korean EEG as a cross-sectional study. Three hundred eighteen healthy children who have not been diagnosed with neurologic or psychiatric disorders were evaluated (168 girls and 150 boys; mean age of 11.8 ± 3.6 years). Analysis indicators were a dietary intake checklist for children's nutrition-related behavior score (NBS), consisting of 19 items; food frequency questionnaires (FFQs), consisting of 76 items; the Child Depression Inventory (CDI); State-Trait Anxiety Inventory-State (STAI-S); State-Trait Anxiety Inventory-Trait (STAI-T); electroencephalograph (EEG); and heart rate variability (HRV). RESULTS: Higher scores on the CDI, STAI-S, and STAI-T indicate negative emotions, and these scores were significantly decreased from the first to the fourth quartiles. The HRV results showed that the standard deviation of all normal-to-normal (SDNN) intervals was significantly higher in the first quartile than in the fourth quartile (p < 0.05). The intakes of artificial sweeteners and processed foods such as hamburgers correlate with higher theta/beta ratios, and intakes of natural foods such as legumes and fruits correlate with lower theta/beta ratios (p < 0.05). CONCLUSIONS AND IMPLICATIONS: From this result we confirmed a link between overall nutritional behavior, food additive intakes, and emotion in apparently healthy children and adolescents.

Feasibility of Robot - assisted Segmental Ureterectomy and Ureteroureterostomy in Patient with High Medical Comorbidity.

INTRODUCTION AND OBJECTIVES: Nephroureterectomy remains the gold standard treatment option for upper tract tumors. However, segmental ureterectomy may be another option in patients with single kidney, borderline renal function or high medical comorbidities. The aim of this video is to assess the feasibility of robotic surgery as a minimally invasive technique in treatment of a high comorbid patient with ureteric tumor. MATERIALS AND METHODS: Eighty-year old male patient, with a medical history of chronic hypertensive and uncontrolled Diabetes Mellitus, was referred to our department for treatment of ureteric tumor. Patient underwent robot-assisted radical prostatectomy 5 years ago. Patient's Charlson comorbidity index score was 9. Computed tomography showed a 2.5cm right ureteral luminal filling enhancing lesion at lower part of upper 1/3 ureter. We performed diagnostic flexible cystoscopy under local anesthesia to exclude associated lower urinary tract carcinoma, and bladder wash was negative for malignancy. Under general anesthesia patient underwent diagnostic flexible ureteroscopy to confirm mass location, and a retrograde pyelography to rule out additional tumors on the right collecting system. Then, the patient was placed in the full lateral flank position without Table flexion. Ports placement were inserted as follow: a "12mm" optical trocar at pararectal line superior and lateral to umbilicus, two "8mm" robotic trocars cranial and caudal to optical trocar (8cm distance), a "8mm" robotic trocar towards anterior superior ischial spine, and a "12mm" assistant trocar was inserted between umbilicus and pubic bone. The surgical steps are shown in the video. RESULTS: The procedure was performed easily. The total operative time and consol time were 100 and 60 minutes, respectively. Blood loss was 50ml. No reported intraoperative or postoperative complications. Notably, we took full precautions in case of intraoperative failure to complete the procedure successfully, nephroureterectomy was our second option. Postoperative serum creatinine was 1.2mg/dL and length of hospital stay was 2 days. The frozen biopsy showed that the tumor was resected with safe proximal and distal surgical margins. Final histopathology revealed high grade (G3) urothelial carcinoma (pT3), measures (1.3x1.2x0.2cm), associated with carcinoma in situ. CONCLUSION: We affirm that robotic segmental ureterectomy and ureteroureterostomy could be offered safely as a minimally invasive treatment for patients with ureteric tumors and high-risk medical comorbidities. It provides excellent perioperative outcomes and early oncological safety with regard to surgical margins.

Sorbus alnifolia protects dopaminergic neurodegeneration in Caenorhabditis elegans.

CONTEXT: The twigs of Sorbus alnifolia (Sieb. et Zucc.) K. Koch (Rosaceae) have been used to treat neurological disorders as a traditional medicine in Korea. However, there are limited data describing the efficacy of S. alnifolia in Parkinson's disease (PD). OBJECTIVE: This study was conducted to identify the protective effects of the methanol extracts of S. alnifolia (MESA) on the dopaminergic (DA) neurodegeneration in Caenorhabditis elegans. MATERIALS AND METHODS: To test the neuroprotective action of MESA, viability assay was performed after 48 h exposure to 1-methyl-4-phenylpyridine (MMP+) in PC12 cells and C. elegans (400 µM and 2 mM of MMP+, respectively). Fluorescence intensity was quantified using transgenic mutants such as BZ555 (Pdat-1::GFP) and and UA57 (Pdat-1::GFP and Pdat-1::CAT-2) to determine MESA's effects on DA neurodegeneration in C. elegans. Aggregation of α-synuclein was observed using NL5901 strain (unc-54p::α-synuclein::YFP). MESA's protective effects on the DA neuronal functions were examined by food-sensing assay. Lifespan assay was conducted to test the effects of MESA on the longevity. RESULTS: MESA restored MPP+-induced loss of viability in both PC12 cells and C. elegans (85.8% and 54.9%, respectively). In C. elegans, MESA provided protection against chemically and genetically-induced DA neurodegeneration, respectively. Moreover, food-sensing functions were increased 58.4% by MESA in the DA neuron degraded worms. MESA also prolonged the average lifespan by 25.6%. However, MESA failed to alter α-synuclein aggregation. DISCUSSION AND CONCLUSIONS: These results revealed that MESA protects DA neurodegeneration and recovers diminished DA neuronal functions, thereby can be a valuable candidate for the treatment of PD.

Robot-assisted Fallopian tube transection and anastomosis using the new REVO-I robotic surgical system: feasibility in a chronic porcine model.

OBJECTIVES: To evaluate the feasibility and safety of the new REVO-I robotic platform by performing Fallopian tube transection and anastomosis in live porcine models. SUBJECTS AND METHODS: A prospective chronic animal study was carried out in four crossbred female pigs. The primary outcome was assessment of the pigs' 2-week survival. The secondary outcomes were measurements of intra-operative variables and the complications or difficulties arising when using the REVO-I. RESULTS: Fallopian tube anastomosis was successfully performed in four porcine models. The mean (range) operating time was 66 (46-104 min), docking time 22.25 (14-53) min and console time 18 (13-20) min. The REVO-I robotic system functioned appropriately, with no technical problems or difficulties noted during the procedures. Both the surgeon and the bedside assistants reported ease of use and better performance with subsequent procedures. All pigs were alive 2 weeks after surgery, with no peri-operative complications related to the use of the robot. CONCLUSIONS: This preclinical chronic porcine study showed that the REVO-I robotic surgical system is a feasible and safe robotic instrument that can be used by surgeons to perform skillful robotic procedures in porcine models. Our next objective will be to demonstrate its safety in humans.

Topographical relationships between the obturator nerve, artery, and vein in the lateral pelvic wall.

INTRODUCTION AND HYPOTHESIS: The aims of this study were to determine the topographical relationships between the obturator nerve (ON), artery (OA), and vein (OV) in the lateral pelvic wall. METHODS: One hundred and fifty hemipelvises of 84 Korean cadavers were dissected. RESULTS: The ON, OA, and OV ran in that order (from upper to lower) within the lateral pelvic wall in 46.7 % of specimens. In 32 % of cases, the three structures were separated at the posterior portion of the wall and then converged toward the obturator canal (OC). In 10 %, the OA and OV were in contact with each other and separate from the ON; in 2 %, the ON was contiguous with the OA and separate from the OV; in 2.7 %, all three structures were in contact with each another. Alternately, the order of ON, OA, and OV was altered in the lateral pelvic wall in 41.3 % of specimens. Finally, in 12 % specimens, either the OA or OV or both were absent from the lateral pelvic wall. CONCLUSIONS: The possibility of the presence of either the OA or OV being between the ON and the external iliac vein, and the potential contact between the ON and either the OA or OV in the lateral pelvic wall, should be borne in mind during pelvic procedures.

Stratified analysis of 800 Asian patients after robot-assisted radical prostatectomy with a median 64 months of follow up.

OBJECTIVE: To report the 5-year oncological outcomes of robot-assisted radical prostatectomy from the largest series ever reported from Asia. METHODS: A retrospective analysis of 800 Asian patients who were treated with robot-assisted radical prostatectomy from July 2005 to May 2010 in the Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Seoul, Korea was carried out. The primary end-point was to evaluate the biochemical recurrence. The secondary end-point was to show the biochemical recurrence-free survival, metastasis-free survival and cancer-specific survival. RESULTS: A total of 197 (24.65%), 218 (27.3%), and 385 (48.1%) patients were classified as low-, intermediate- and high-risk patients according to the D'Amico risk stratification risk criteria, respectively. The median follow-up period was 64 months (interquartile range 28-71 months). The overall incidence of positive surgical margin was 36.6%. There was biochemical recurrence in 183 patients (22.9%), 38 patients (4.8%) developed distant metastasis and 24 patients (3%) died from prostate cancer. Actuarial biochemical recurrence-free survival, metastasis-free survival, and cancer-specific survival rates at 5 years were 76.4%, 94.6% and 96.7%, respectively. Positive lymph node was associated with lower 5-year biochemical recurrence-free survival (9.1%), cancer-specific survival (75.7%) and metastasis-free survival (61.9%) rates (P < 0.001). On multivariable analysis, among all the predictors, positive lymph node was the strongest predictor of biochemical recurrence, cancer-specific survival and metastasis-free survival (P < 0.001). CONCLUSIONS: Herein we report the largest robot-assisted radical prostatectomy series from Asia. Robot-assisted radical prostatectomy is confirmed to be an oncologically safe procedure that is able to provide effective 5-year cancer control, even in patients with high-risk disease.

Robot-assisted partial nephrectomy confers excellent long-term outcomes for the treatment of complex cystic renal tumors: Median follow up of 58 months.

OBJECTIVES: To analyze long-term outcomes of robot-assisted partial nephrectomy for treatment of complex cystic renal tumors. METHODS: We retrospectively analyzed the data of patients who underwent robot-assisted partial nephrectomy for cystic (n = 32) and solid (n = 263) renal masses at Severance Hospital, Seoul, Korea. The primary outcome was assessment of perioperative safety for cystic tumor. Secondary outcomes were evaluation of long-term oncological and functional results. RESULTS: Patients' clinical and demographic characteristics were similar among both groups. The median follow up of cystic and solid masses were 58 and 46 months, respectively. Cystic masses were more likely to have low Fuhrman grade 1 and 2 (P = 0.03), and shorter operative time (P = 0.04) compared with solid masses. There was no statistically significant difference regarding warm ischemia time, estimated blood loss, trifecta achievement, length of hospital stay, complication rates and renal function preservation (P > 0.05) between groups. In the solid group, 12 patients (4.1%) recurred, and six patients (2%) died from metastatic renal cell carcinoma, whereas the patients in the cystic group did not have any local or distance recurrence, and the survival rates were 100%. The 5-year cancer-free survival (P = 0.77), cancer-specific survival (P = 0.65) and overall survival (P = 0.83) rates were similar between the groups. CONCLUSION: Robot-assisted partial nephrectomy appears to be safe and feasible treatment for complex cystic renal masses. It confers excellent long-term oncological outcomes. Robot-assisted partial nephrectomy should be the treatment of choice for complex cysts whenever feasible.

Robot-assisted Partial Nephrectomy for Endophytic Tumors.

Robot-assisted partial nephrectomy (RAPN) has gained increasing popularity in the management of renal masses due to its technical feasibility and shorter learning curve with superior perioperative outcomes compared to laparoscopic partial nephrectomy (LPN). Given the cumulation of surgical experience on RAPN, the indication for RAPN has been extended to more challenging, complex cases, such as hilar or endophytic tumors. Renal masses that are completely endophytic can be very challenging to surgeons. These cases are associated with poor recognition of mass extension, higher risk of inadvertent vascular, or pelvicalyceal system injury. As a result, this can lead to potential positive surgical margin, difficulty in performing renorrhaphy as well as higher perioperative complication rates. There is few evidence of oncologic and functional outcomes of RAPN on treating endophytic masses. Therefore, the objective of this review is to critically analyze the current evidence and to provide a summary on the outcomes of RAPN for endophytic renal masses.

Two-year analysis for predicting renal function and contralateral hypertrophy after robot-assisted partial nephrectomy: A three-dimensional segmentation technology study.

OBJECTIVES: To analyze long-term changes in both kidneys, and to predict renal function and contralateral hypertrophy after robot-assisted partial nephrectomy. METHODS: A total of 62 patients underwent robot-assisted partial nephrectomy, and renal parenchymal volume was calculated using three-dimensional semi-automatic segmentation technology. Patients were evaluated within 1 month preoperatively, and postoperatively at 6 months, 1 year and continued up to 2-year follow up. Linear regression models were used to identify the factors predicting variables that correlated with estimated glomerular filtration rate changes and contralateral hypertrophy 2 years after robot-assisted partial nephrectomy. RESULTS: The median global estimated glomerular filtration rate changes were -10.4%, -11.9%, and -2.4% at 6 months, 1 and 2 years post-robot-assisted partial nephrectomy, respectively. The ipsilateral kidney median parenchymal volume changes were -24%, -24.4%, and -21% at 6 months, 1 and 2 years post-robot-assisted partial nephrectomy, respectively. The contralateral renal volume changes were 2.3%, 9.6% and 12.9%, respectively. On multivariable linear analysis, preoperative estimated glomerular filtration rate was the best predictive factor for global estimated glomerular filtration rate change on 2 years post-robot-assisted partial nephrectomy (B -0.452; 95% confidence interval -0.84 to -0.14; P = 0.021), whereas the parenchymal volume loss rate (B -0.43; 95% confidence interval -0.89 to -0.15; P = 0.017) and tumor size (B 5.154; 95% confidence interval -0.11 to 9.98; P = 0.041) were the significant predictive factors for the degree of contralateral renal hypertrophy on 2 years post-robot-assisted partial nephrectomy. CONCLUSIONS: Preoperative estimated glomerular filtration rate significantly affects post-robot-assisted partial nephrectomy renal function. Renal mass size and renal parenchyma volume loss correlates with compensatory hypertrophy of the contralateral kidney. Contralateral hypertrophy of the renal parenchyma compensates for the functional loss of the ipsilateral kidney.

An analysis of Y-chromosome microdeletion in infertile Korean men with severe oligozoospermia or azoospermia.

PURPOSE: Infertility affects 10% to 15% of couples, and male factor accounts for 50% of the cases. The relevant male genetic factors, which account for at least 15% of male infertility, include Y-chromosome microdeletions. We investigated clinical data and patterns of Y-chromosome microdeletions in Korean infertile men. MATERIALS AND METHODS: A total of 919 infertile men whose sperm concentration was ≤5 million/mL in two consecutive analyses were investigated for Y-chromosome microdeletion. Among them, 130 infertile men (14.1%) demonstrated Y-chromosome microdeletions. Medical records were retrospectively reviewed. RESULTS: In 130 men with Y-chromosome microdeletions, 90 (69.2%) had azoospermia and 40 (30.8%) had severe oligozoospermia. The most frequent microdeletions were in the azoospermia factor (AZF) c region (77/130, 59.2%), followed by the AZFb+c (30/130, 23.1%), AZFa (8/130, 6.2%), AZFb (7/130, 5.4%), AZFa+b+c (7/130, 5.4%), and AZFa+c (1/130, 0.7%) regions. In men with oligozoospermia, 37 (92.5%) had AZFc microdeletion. Chromosomal abnormalities were detected in 30 patients (23.1%). Higher follicle-stimulating hormone level (23.2±13.5 IU/L vs. 15.1±9.0 IU/L, p<0.001), higher luteinizing hormone level (9.7±4.6 IU/L vs. 6.0±2.2 IU/L, p<0.001), and lower testis volume (10.6±4.8 mL vs. 13.3±3.8 mL, p<0.001) were observed in azoospermia patients compared to severe oligozoospermia patients. CONCLUSIONS: Y-chromosome microdeletion is a common genetic cause of male infertility. Therefore, Y-chromosome microdeletion test is recommended for the accurate diagnosis of men with azoospermia or severe oligozoospermia. Appropriate genetic counseling is mandatory before the use of assisted reproduction technique in men with Y-chromosome microdeletion.

Oxidative tryptamine dimers from Corynebacterium durum directly target survivin to induce AIF-mediated apoptosis in cancer cells.

Accumulating evidence indicates that microbial communities in the human body crucially affect health through the production of chemical messengers. However, the relationship between human microbiota and cancer has been underexplored. As a result of a biochemical investigation of the commensal oral microbe, Corynebacterium durum, we identified the non-enzymatic transformation of tryptamine into an anticancer compound, durumamide A (1). The structure of 1 was determined using LC-MS and NMR data analysis as bis(indolyl)glyoxylamide, which was confirmed using one-pot synthesis and X-ray crystallographic analysis, suggesting that 1 is an oxidative dimer of tryptamine. Compound 1 displayed cytotoxic activity against various cancer cell lines with IC50 values ranging from 25 to 35 µM. A drug affinity responsive target stability assay revealed that survivin is the direct target protein responsible for the anticancer effect of 1, which subsequently induces apoptosis-inducing factor (AIF)-mediated apoptosis. Inspired by the chemical structure and bioactivity of 1, a new derivative, durumamide B (2), was synthesized using another indole-based neurotransmitter, serotonin. The anticancer properties of 2 were similar to those of 1; however, it was less active. These findings reinforce the notion of human microbiota-host interplay by showing that 1 is naturally produced from the human microbial metabolite, tryptamine, which protects the host against cancer.

Phenylacetic acid, an anti-vaginitis metabolite produced by the vaginal symbiotic bacterium Chryseobacterium gleum.

The human microbiome contains genetic information that regulates metabolic processes in response to host health and disease. While acidic vaginal pH is maintained in normal conditions, the pH level increases in infectious vaginitis. We propose that this change in the vaginal environment triggers the biosynthesis of anti-vaginitis metabolites. Gene expression levels of Chryseobacterium gleum, a vaginal symbiotic bacterium, were found to be affected by pH changes. The distinctive difference in the metabolic profiles between two C. gleum cultures incubated under acidic and neutral pH conditions was suggested to be an anti-vaginitis molecule, which was identified as phenylacetic acid (PAA) by spectroscopic data analysis. The antimicrobial activity of PAA was evaluated in vitro, showing greater toxicity toward Gardnerella vaginalis and Candida albicans, two major vaginal pathogens, relative to commensal Lactobacillus spp. The activation of myeloperoxidase, prostaglandin E2, and nuclear factor-κB, and the expression of cyclooxygenase-2 were reduced by an intravaginal administration of PAA in the vaginitis mouse model. In addition, PAA displayed the downregulation of mast cell activation. Therefore, PAA was suggested to be a messenger molecule that mediates interactions between the human microbiome and vaginal health.

Azoospermic Men with a History of Cryptorchidism Treated by Orchiopexy Have Favorable Outcomes after Testicular Sperm Extraction: A Systematic Review and Meta-Analysis.

PURPOSE: This systematic review and meta-analysis investigated the sperm retrieval rate (SRR) and pregnancy rate after testicular sperm extraction in men with azoospermia and those with a history of cryptorchidism treated by orchiopexy. MATERIALS AND METHODS: The SRR and clinical pregnancy rate were investigated. We performed a sub-analysis that included factors such as bilaterality, age, and idiopathic non-obstructive azoospermia (iNOA). The analysis comprised 13 studies from January 1995 to July 2021. The data sources were PubMed/MEDLINE, Embase, and the Cochrane Library included "cryptorchidism", "orchidopexy", "azoospermia", and "testicular sperm extraction". RESULTS: The overall mean SRR was 63.3% (95% confidence interval [CI], 57.6%-68.6%; I²=62.4%), and the overall mean clinical pregnancy rate was 30.1% (95% CI, 22.6%-38.8%; I²=69.9%). The meta-analysis comparing the SRR, there was no significant difference between patients with a history of bilateral and unilateral orchiopexy (relative risk [RR]=1.02; 95% CI, 0.89-1.16; p=0.79). Orchiopexy performed under the age of 10 years showed significantly increased SRR compared to the age of over 10 years (RR=1.25; 95% CI, 1.06-1.47; p=0.008). Azoospermic men with a history of cryptorchidism treated by orchiopexy had significantly higher SRR than iNOA (RR=1.90; 95% CI, 1.40-2.58; p<0.0001). CONCLUSIONS: Men with azoospermia and a history of cryptorchidism treated by orchiopexy had significantly higher SRR than those with iNOA after testicular sperm extraction. Furthermore, patients who underwent orchiopexy before the age of ten years had significantly higher SRR than patients operated at an older than the age of ten years.

Effect of male age on reproductive function: A comparison of young and middle-aged men.

PURPOSE: There have been concerns regarding potential effects of older paternal age on male reproductive function. However, currently available data on this topic are insufficient and controversy exists. We analyzed semen characteristics and reproductive hormones in young men and middle-aged men to investigate the effect of age on male reproductive function. MATERIALS AND METHODS: This study examined healthy males of reproductive age who visited a single infertility center from January 2016 to July 2021. The young group consisted of men who were less than 35 years-old, and the middle-age group consisted of men who were more than 45 years-old. RESULTS: The two groups had no significant differences in sperm concentration ([89.9±59.4]×106/mL vs. [104.4±82.1]×106/mL, p=0.108) or sperm morphology (normal forms: 3.6%±1.5% vs. 3.4%±1.6%, p=0.131). However, the middle-age group had a smaller semen volume (3.2±1.5 mL vs. 2.5±1.4 mL, p<0.001), lower sperm motility (42.3%±9.8% vs. 31.2%±12.4%, p<0.001), lower progressive sperm motility (39.2%±10.3% vs. 28.4%±12.6%, p<0.001), and a higher serum follicle-stimulating hormone level. CONCLUSIONS: Our results suggest that advanced male age might have a negative effect on fertility potential, as in women. This finding has important clinical implications because more couples are choosing to have children when they are older. Further studies on this issue, especially those that examine reproductive outcome, are warranted.