Non-Invasive Radiofrequency Hyperthermia Attenuates HMGB1/TLR4/NF-κB Inflammatory Axis in a Chronic Prostatitis/Chronic Pelvic Pain Syndrome Rat Model.

PURPOSE: The primary goal of this study is to evaluate the effect of the non-invasive radiofrequency hyperthermia (RFHT) device on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) rat model and investigate the underlying mechanism. MATERIALS AND METHODS: In this study, Sprague-Dawley rats were randomly distributed into three groups: (1) normal control group, (2) CP/CPPS group, and (3) RFHT group. CP/CPPS rat models were induced by 17ß-estradiol and dihydrotestosterone for 4 weeks and RFHT was administered for 5 weeks after model establishment. During RFHT administration, core body temperatures were continuously monitored with a rectal probe. After administering RFHT, we assessed pain index for all groups and collected prostate tissues for Western blot analysis, immunofluorescence, and immunohistochemistry. We also collected adjacent organs to the prostate including urinary bladder, testes, and rectum for safety assessment via H&E staining along with a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay. RESULTS: After administering RFHT, pain in rats was significantly alleviated compared to the CP/CPPS group. RFHT reduced high-mobility group box 1 (HMGB1) expression and improved inflammation by downregulating subsequent proinflammatory cytokines through inhibition of the toll-like receptor 4 (TLR4)-nuclear factor kappa B (NF-κB) pathway. In prostate-adjacent organs, no significant histological alteration or inflammatory infiltration was detected. The area of cell death also did not increase significantly after RFHT. CONCLUSIONS: In conclusion, RFHT demonstrated anti-inflammatory effects by inhibiting the HMGB1-TLR4-NF-κB pathway in CP/CPPS rat models. This suggests that RFHT could serve as a safe and promising therapeutic strategy for CP/CPPS.

A Comparative Analysis between Flexible Ureteroscopic Lithotripsy and Tubeless Percutaneous Nephrolithotomy in the Treatment of >15 mm Non-Obstructing Proximal Ureteral Stones.

BACKGROUND: The proper surgical modality for large non-obstructing proximal ureteral stones is disputed. We compare effectiveness and safety of flexible ureteroscopic lithotripsy (FURL) and tubeless percutaneous nephrolithotomy (TPNL) in treatment of upper ureteral stones larger than 1.5 cm. METHODS: We reviewed the medical records of patients who performed FURL or TPNL for upper ureteral stones between June 2016 and November 2018. Comparative analysis was conducted regarding demographic parameters, stone free rate, postoperative pain and complications. RESULTS: This study included 58 patients treated with FURL and 60 patients treated with TPNL owing to upper ureteral stones larger than 1.5 cm. Stone size was similar in the FURL and TPNL groups (17.6 ± 2.6 vs. 18.0 ± 2.1 mm, p = 0.194). The overall 3-month stone clearance rate was 95.8% for FURL versus 96.0% for TPNL (p = 0.575). There was no difference between the FURL and TPNL groups for hospital stay (p = 0.280) and postoperative complications. On the other hand, patients treated with FURL had longer operative time (p = 0.012) and less postoperative pain (p = 0.008). CONCLUSIONS: Both surgical techniques were considered feasible and effective surgical procedures in the treatment of large upper ureteral stones.

Impact of carrier hydrophilicity on solid self nano-emulsifying drug delivery system and self nano-emulsifying granule system.

The purpose of this study was to investigate the impact of carrier hydrophilicity on solid self nano-emulsifying drug delivery system (SNEDDS) and self nano-emulsifying granule system (SEGS). The mesoporous calcium silicate (Ca-silicate) and hydroxypropyl-ß-cyclodextrin (HP-ß-CD) were utilised as hydrophobic carrier and hydrophilic carrier, respectively. The liquid SNEDDS formulation, composed of Tween80/Kollipohr EL/corn oil (35/50/15%) with 31% (w/w) dexibuprofen, was spray-dried and fluid-bed granulated together with Avicel using Ca-silicate or HP- ß-CD as a solid carrier, producing four different solid SNEDDS and SEGS formulations. Unlike the Ca-silicate-based systems, spherical shape and aggregated particles were shown in HP-ß-CD-based solid SNEDDS and SEGS, respectively. Molecular interaction was detected between Ca-silicate and the drug; though, none was shown between HP-ß-CD and the drug. Each system prepared with either carrier gave no significant differences in micromeritic properties, crystallinity, droplet morphology, size, dissolution and oral bioavailability in rats. However, the HP-ß-CD-based system more significantly improved the drug solubility than did the Ca-silicate-based system. Therefore, both carriers hardly affected the properties of both solid SNEDDS and SEGS; though, there were differences in the aspect of appearance, molecular interaction and solubility.

Peri-Incisional Infiltration and Intraperitoneal Instillation of Local Anesthetic for Reducing Pain After Laparoscopic Donor Nephrectomy: A Prospective, Randomized, Double-Blind Control Trial.

BACKGROUND: The analgesic efficacy of peri-incisional infiltration and intraperitoneal instillation of ropivacaine in laparoscopic donor nephrectomy has not been clearly established. METHODS: This randomized, controlled, double-blind trial allocated living donors undergoing left-sided laparoscopic donor nephrectomy to one of the following 4 groups: peri-incisional normal saline (NS) and intraperitoneal NS (group A, n = 30), peri-incisional 0.375% ropivacaine and intraperitoneal NS (group B, n = 31), peri-incisional NS and intraperitoneal 0.15% ropivacaine (group C, n = 31), and peri-incisional 0.375% and intraperitoneal 0.15% ropivacaine (group D, n = 32). Pain status was assessed using the visual analog scale at rest and during coughing at 2, 12, 24, and 48 hours postoperatively. Patient-controlled analgesia and additional rescue analgesic consumption were calculated by conversion to an equivalent dosage of morphine. This study did not include prisoners or those individuals who were coerced or paid as study participants. RESULTS: The patient demographics and perioperative outcomes, including operative time, blood loss, and incision length, were comparable between the groups. The pain scores and number of patients who experienced shoulder pain at all postoperative time points did not differ significantly among the 4 groups. Postoperative analgesic consumption was similar in all groups, and there was no difference in the length of hospital stay. CONCLUSION: Peri-incisional infiltration and intraperitoneal instillation of ropivacaine did not reduce postoperative pain or analgetic consumption.

Development of Novel Tamsulosin Pellet-Loaded Oral Disintegrating Tablet Bioequivalent to Commercial Capsule in Beagle Dogs Using Microcrystalline Cellulose and Mannitol.

In this study, we developed a tamsulosin pellet-loaded orally disintegrating tablet (ODT) that is bioequivalent to commercially available products and has improved patient compliance using microcrystalline cellulose (MCC) and mannitol. Utilizing the fluid bed technique, the drug, sustained release (SR) layer, and enteric layer were sequentially prepared by coating MCC pellets with the drug, HPMC, Kollicoat, and a mixture of Eudragit L and Eudragit NE, respectively, resulting in the production of tamsulosin pellets. The tamsulosin pellet, composed of the MCC pellet, drug layer, SR layer, and enteric layer at a weight ratio of 20:0.8:4.95:6.41, was selected because its dissolution was equivalent to that of the commercial capsule. Tamsulosin pellet-loaded ODTs were prepared using tamsulosin pellets and various co-processed excipients. The tamsulosin pellet-loaded ODT composed of tamsulosin pellets, mannitol-MCC mixture, silicon dioxide, and magnesium stearate at a weight ratio of 32.16:161.84:4.0:2.0 gave the best protective effect on the coating process and a dissolution profile similar to that of the commercial capsule. Finally, no significant differences in beagle dogs were observed in pharmacokinetic parameters, suggesting that they were bioequivalent. In conclusion, tamsulosin pellet-loaded ODTs could be a potential alternative to commercial capsules, improving patient compliance.

Retroperitoneal Single-Port Robot-Assisted Nephroureterectomy with Bladder Cuff Excision: Initial Experience and Description of the Technique.

BACKGROUND: With the introduction of the single-port (SP) robot, surgery that was difficult to attempt is becoming possible. Nephroureterectomy (NUx) for upper tract urothelial carcinoma also seems to be able to attempt a retroperitoneal (RP) approach. PURPOSE: to investigate the feasibility of SP robotic RP NUx with bladder cuff excision. DESIGN, SETTING, AND PARTICIPANTS: we sequentially analyzed 20 patients who underwent SP robot NUx from January 2021 to December 2022. SURGICAL PROCEDURE: all patients were diagnosed with upper tract urothelial carcinoma (UTUC) and were operated upon by a single expert using the da Vinci SP platform (Intuitive Surgical, Sunnyvale, CA, USA) with retroperitoneal approach. RESULTS AND LIMITATIONS: A total of 20 patients underwent SP robotic NUx with bladder cuff excision. The mean age of patients was 69.45 ± 8.68 years, and the mean body mass index (BMI) was 25.37 ± 3.00 kg/m2. The mean tumor size was 2.42 ± 1.03 cm on a CT scan, with right-sided tumors in eight patients (40%) and left-sided tumors in 12 patients (60%). The median console time was 106 min and 40 s, and the expected blood loss was 122.50 ± 75.18 mL. Final pathology showed that all of the patients were diagnosed as having urothelial carcinoma; one patient was classified as Ta (5.00%), three patients were classified as T1 (15.00%), seven patients were classified as T2 (35.00%), eight patients were classified as T3 (40.00%), and one patient was classified as T4 (5.00%). None of these 20 patients showed any complications based on the Clavien-Dindo scale. CONCLUSIONS: SP robotic NUx using a retroperitoneal approach provides feasible perioperative and postoperative outcomes for UTUC.

Urethra-Sparing Robot-Assisted Simple Prostatectomy for Postoperative Antegrade Ejaculation.

BACKGROUND: We report a comparative analysis of extraperitoneal urethra-sparing robot-assisted simple prostatectomy (EUS-RASP) versus robot-assisted simple prostatectomy (RASP) using the Freyer approach for patients with a large prostate volume greater than 80 mL. METHODS: A total of 32 patients underwent EUS-RASP, and 30 underwent RASP from April 2018 to November 2021. All the perioperative data and 6-month follow-up data were collected prospectively. We retrospectively evaluated baseline characteristics and functional outcomes, including International Prostate Symptom Scores (IPSSs) and quality of life (QOL), maximum flow rate, and post-void residual volume, between the two groups. Sexual function was analyzed in the EUS-RASP group. RESULTS: The patients undergoing EUS-RASP and RASP had comparable baseline characteristics and functional outcomes. The EUS-RASP group showed a shorter operative time (123.4 ± 15.2 min vs. 133.7 ± 21.4 min, p = 0.034), length of hospital stay (2.9 ± 1.5 days vs. 4.6 ± 1.5 days, p = 0.001), and catheterization time (2.4 ± 1.7 days vs. 8.1 ± 2.4 days, p < 0.001). A total of 14/32 (43.8%) patients reported normal preoperative ejaculatory function in the EUS-RASP group, and 11/14 (78.6%) maintained antegrade ejaculation postoperatively. CONCLUSIONS: Extraperitoneal urethra-sparing RASP is an effective and feasible procedure that can improve voiding function and allow for the maintenance of ejaculatory function in patients with large prostates.

Impact of Particulate Matter With an Aerodynamic Diameter <2.5 µm Concentration on Postoperative Renal Function in Living Kidney Donors.

BACKGROUND: Ambient air pollution has become 1 of the most important public health issues worldwide. In particular, particulate matter with an aerodynamic diameter <2.5 µm (PM2.5) is a fatal component of air pollution. We aimed to analyze whether perioperative exposure to PM2.5 is associated with the deterioration of renal function in living kidney donors. METHODS: This study was conducted on 232 kidney donors with postoperative 2-year glomerular filtration rate (GFR). The GFR was determined by serum creatinine-based method using the Modification of Diet in Renal Disease equation and radionuclide-based method using 99mTc-DTPA renal scintigraphy. Perioperative exposure to PM2.5 was calculated using data from the AIRKOREA System. Multiple linear and logistic regression analyses were performed to estimate the associations between mean PM2.5 concentration and postoperative 2-year GFR. RESULTS: Postoperative Modification of Diet in Renal Disease-estimated GFRs of kidney donors with low PM2.5 concentrations were significantly higher than those of those with high PM2.5 concentrations. A 1-µg/m3 increase in mean PM2.5 concentration was associated with decreased GFR by 0.20 mL/min/1.73 m2. In addition, a 1-µg/m3 increase in mean PM2.5 concentration was associated with an 11% increased risk of chronic kidney disease stage ≥3 at 2 years after donor nephrectomy. CONCLUSION: In patients who underwent donor nephrectomy, exposure to PM2.5 negatively affects renal function and is positively associated with the prevalence of chronic kidney disease.

Comparing 12-core and 20-core biopsy for prostate cancer diagnosis with transperineal MR/US fusion biopsy: assessing the effective number of systemic cores using propensity score matching.

PURPOSE: For transperineal (TP) prostate biopsy, target biopsy for visible lesions on MRI is important, but there is no consensus of the number of systemic biopsy cores. Our study aimed to confirm the diagnostic efficiency of 20-core systemic biopsy by comparison with 12-core using propensity score matching (PSM). METHODS: The 494 patients conducted the naive TP biopsy were retrospectively analyzed. There were 293 patients with 12-core biopsy and 201 patients with 20-core biopsy. PSM was performed for minimizing confounding variables, and the established effects' value was analyzed for 'index-positive or negative' clinically significant prostate cancer (csPCa) (Index means PIRADS Score ≥ 3 on multiparametric prostate MRI). RESULTS: At 12-core biopsy, there were 126 cases of prostate cancer (43.0%), and 97 cases of csPCa (33.1%). At 20-core biopsy, there were 91 cases (45.3%) and 63 cases (31.3%). After propensity score matching, for index-negative csPCa, the estimated odds ratio was 4.03 (95% CI 1.35-12.09, p value 0.0128), and for index-positive csPCa, the estimated odds ratio was 0.98 (95% CI 0.63-1.52, p value 0.9308). CONCLUSIONS: The 20-core biopsy did not show a higher detection rate for csPCa in comparison with the 12-core biopsy. However, when MRI did not show a suspicious lesion, 20-core biopsy showed higher odd ratio in comparison with 12-core biopsy. Therefore, if there is a suspicious lesion in MRI, 20-core biopsy is excessive and 12-core biopsy is sufficient. Whereas if there is no suspicious lesion in MRI, it is better to proceed with 20-core biopsy.

Magnetic delivery and ultrasound-responsive release of chelating microcapsules for selective removal of urolithiasis.

A novel urolithiasis treatment in which a chelating solution encapsulated in poly(lactic-co-glycolic acid); PLGA-based microcapsules was delivered magnetically to specific urolithiasis sites and then subjected to ultrasound (US) to release the chelating solution and dissolve the stones. Using a double-droplet microfluidics method, a hexametaphosphate (HMP) chelating solution was encapsulated in an Fe3O4 nanoparticle (Fe3O4 NP)-loaded PLGA polymer shell with a thickness of <15 µm, forming homogenous microcapsules of 319 ± 14 µm in size. The obtained microcapsules (HMP/Fe3O4@PLGA) exhibited efficient magnetic mobility and US-responsive solution release. Moreover, in a Ψ-shaped flow chip, selective delivery of HMP from the microcapsules was achieved with high magnetic delivery efficiency (>90%), and an effective removal efficacy (>95%, 7 repeat cycles) of artificial calcium oxalate (5 mm in size) via a chelating effect. Eventually, the potential removal of urolithiasis in the body was verified using a PDMS-based kidney urinary flow-imitating chip with a human kidney stone (CaOx 100%, 5-7 mm in size) located in the minor calyx under an artificial urine counter flow (0.5 mL min-1). In the end, more than 50% of the stone, even in surgically tricky regions, was removed by 10 repeated treatments. Therefore, the selective approach of stone-dissolution capsules will help to develop alternative urolithiasis treatments to conventional surgical and systemic dissolution approaches.

Irreversible electroporation for prostate cancer using PSMA PET-CT.

Background: To demonstrate the clinical usefulness of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) computerized tomography (CT) for irreversible electroporation (IRE) in prostate cancer patients. Methods: From January to May 2021, 17 men were diagnosed with localized prostate cancer through preoperative mpMRI and [18F] florastamin PSMA PET-CT imaging, followed by transperineal MRI-ultrasound fusion-guided biopsy. The patients underwent IRE focal therapy at the target lesions under general anesthesia. To evaluate the treatment outcome, serum prostate-specific antigen (PSA) levels were followed up in the 1st, 3rd, 6th, 9th, 12th months, and mpMRI was taken in the 1st and 12th months, followed by MR fusion biopsy in the 12th month post-IRE. Results: The mean age of the patients was 66.1 ± 9.3 with a median PSA of 7.5 ng/ml. After the treatment, PSA nadir was 4.06 ± 3.4, and 11 (64.7%) achieved decline of PSA more than 50% from the baseline. Rate of negative biopsy for prostate cancer is 88% (15/17) at 12 months MR fusion biopsy after the IRE treatment. Among the relapsed cases, 1 (6.9%) patient recurred at margin of treated area, and 1 (6.9%) patient was from outfield recurrence. When excluding initial four patients, none of the patients had cancer recur. Conclusions: When treating with IRE focal therapy, PSMA-PET CT is a potentially valuable diagnostic approach for localizing prostate cancer; it supports the detection of lesions with conventional mpMRI, enabling to perform the procedure more completely.

Characteristics of recurrent acute urinary retention in BPH patients in the United States: Retrospective analysis of US-based insurance claims database.

PURPOSE: The objective of this study is to analyze characteristics of recurrent acute urinary retention (AUR) in patients with benign prostatic hyperplasia (BPH), utilizing a population based data set. Also, we sought to report on how AUR was treated, specifically regarding the need and length of catheterization and types of procedures utilized for mitigation. MATERIALS & METHODS: A retrospective observational cohort study was performed using Optum's deidentified Clinformatics® Data Mart Database. We compared two groups, BPH patients with AUR (n = 180,737) and BPH patients without AUR (n = 1,139,760) from January 1, 2003 to December 31, 2017. Also, we analyzed the factors affecting the development of multiple episodes of AUR through age-adjusted multivariate analysis. RESULTS: In contrast to the 47.7% of patients who had a single AUR episode, 33.5% of AUR patients developed 3 or more subsequent episodes of retention. For age matched patients, the risks of additional episodes of retention increase significantly with older age, Caucasian race, diabetes, neurologic conditions, or low income. Overall, the rate of BPH surgery in AUR patients over the study period decreased and the most common procedure was transurethral resection of the prostate. CONCLUSIONS: Risk factors for multiple episodes of AUR included age (60 and older), Caucasian race, lower income socioeconomic status, diabetes, and neurological disorders. Patients with a high probability of developing recurrent episodes of AUR are recommended to receive preemptive BPH medication before such AUR occurrences. Also, more expeditious surgical treatment should be considered rather than temporary catheterization when AUR occurs.

Are hemostatic agents for selective cases of tubeless percutaneous nephrolithotomy necessary for access tract control? A randomized control trial.

PURPOSE: To evaluate the efficacy of percutaneous nephrolithotomy (PCNL) access tract sealing agent. Fibrin glue and Tachosil® were used for sealing the access tract and compared to the control. Post operative computed tomography (CT) scan was used to evaluate those efficacies. METHODS: A total of 108 patients were randomized to three groups: In group 1, the access tract was sutured, and compressive dressing was done. In group 2, the fibrin glue was injected into the access tract with a tip applicator at the end of operation. And group 3, Tachosil® was rolled on its longitudinal axis and plugged into the access tract. Non-contrast CT at POD 1 was taken and perirenal hematoma thickness was measured and graded. Hemoglobin, hematocrit, VAS score, stone-free status, and hospital stay were analyzed. RESULTS: Preoperative demographic differences were not significant in all three arms. Postoperative CT scans in all groups demonstrated mostly minimal grade access tract hematomas. Mean perirenal hematoma thickness showed no significant differences (2.66 ± 3.74, 2.73 ± 3.85, 2.54 ± 4.37 mm, p = 0.981), respectively. Postoperative hemoglobin drop (0.75 ± 0.58, 0.84 ± 0.47, 0.91 ± 0.60 g/dl, p = 0.74), stone-free rate (93.75, 87.87, 87.87%, p = 0.121), VAS (p = 0.499) and hospital stay (1.81 ± 0.84, 1.48 ± 0.71, 1.59 ± 0.75 day, p = 0.127) were not significantly different between the groups. CONCLUSION: Fibrin glue and Tachosil® in tubeless PCNL were not necessary for postoperative access tract control.

Comparison of Transperitoneal and Retroperitoneal Partial Nephrectomy with Single-Port Robot.

Purpose: To investigate the efficacy and safety of single-port (SP) robotic transperitoneal (TP) and retroperitoneal (RP) partial nephrectomy. Materials and Methods: We sequentially analyzed 30 partial nephrectomy performed after the SP robot was introduced to the hospital in September 2021 to June 2022. All patients were found to have T1 renal cell carcinoma (RCCs) and were operated by a single expert in conventional robot with da Vinci SP platform. Results: Total of 30 patients underwent SP robotic partial nephrectomy with 16 (53.33%) by TP approach and 14 (47.67%) by RP. Body mass index was slightly higher in TP group (25.37 vs 23.53, p-value = 0.040). The other demographic information was not significantly different. There was no statistical difference in ischemic time (727.41 ± 561.18 seconds for TP and 698.56 ± 299.23 seconds for RP, p-value = 0.812), and console time (67.97 ± 24.06 minutes for TP and 69.71 ± 28.66 minutes for RP, p-value = 0.724). There was no statistical difference in perioperative and pathologic outcomes either. Postoperative renal function calculated from diethylenetriaminepentacetate was 103.33 mL/min/1.73 m2 for TP and 101.33 mL/min/1.73 m2 for RP (p-value = 0.214). And 90.36 mL/min/1.73 m2 for TP and 87.74 mL/min/1.73 m2 for RP at 90 days after surgery (p-value = 0.592). Conclusion: SP robot partial nephrectomy can be performed effectively and safely regardless of the approach. TP and RP approach offers similar perioperative and postoperative outcomes for T1 RCC. The Clinical Trial Registration number KC22WISI0431.

Quisqualis indica extract for men with lower urinary tract symptoms: A randomized, double-blind, placebo-controlled trial.

PURPOSE: To evaluate the efficacy and safety of Quisqualis indica in men with moderate lower urinary tract symptoms (LUTS). MATERIALS AND METHODS: A total of 135 subjects with International Prostate Symptom Score (IPSS) of 8-19 were randomized in 2 centers from June 2018 to April 2019. Patients were assigned into one of the three groups: a low-dose group (LG, 1,000 mg Q. indica), a high-dose group (HG, 2,000 mg Q. indica) or a placebo group (PG). The primary endpoint was the change of IPSS at the end of treatment from baseline. Secondary end points included the changes of prostate specific antigen, testosterone, dihydrotestosterone, maximum urinary flow rate (Qmax), postvoid residual volume (PVR) and International Index of Erectile Function-5 (IIEF-5), with drug safety. RESULTS: 113 patients were able to finish the study. Compared to the PG, total IPSS in the LG and the HG was significantly improved at 6 weeks and 12 weeks. For IPSS subscores, LG showed improvements in all except for urgency and quality of life at 6 weeks. HG showed improvements in incomplete emptying and frequency at 6 weeks and 12 weeks along with improvements in intermittency, straining, and quality of life at 12 weeks. For IIEF-5 subscores, orgasmic function and overall satisfaction improved in HG when compared to PG at 12 weeks. Lastly, increase of Qmax and decrease of PVR was observed at 6 weeks in LG. CONCLUSIONS: 12-week treatment with Q. indica has a therapeutic effect and is well tolerated in patients with LUTS.

Efficacy and Safety of Maca (Lepidium meyenii) in Patients with Symptoms of Late-Onset Hypogonadism: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

PURPOSE: To evaluated the efficacy and safety of gelatinized Maca (Lepidium meyenii) for eugonadal patients with late onset hypogonadism symptoms (LOH). MATERIALS AND METHODS: Participants were instructed to receive 1,000 mg of Maca or placebo, two pills at a time, three times per day for 12 weeks before food intake. To evaluate the efficacy of the drug, Aging Males' Symptoms scale (AMS), Androgen Deficiency in the Aging Males (ADAM), International Prostate Symptom Score (IPSS), and International Index of Erectile Function (IIEF) questionnaires, serologic tests (total testosterone and free testosterone, total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglyceride), body weight, and waist circumference were assessed at 4 and 12 weeks after treatment. RESULTS: A total of 80 participants were enrolled and randomly assigned to Maca treated group (n=41) or the placebo group (n=39). AMS, IIEF, and IPSS were significantly (p<0.05) improved in Maca treated group than in the placebo group. ADAM positive rate was also significantly (p<0.0001) decreased in Maca treated group. CONCLUSIONS: Maca may be considered an effective and safe treatment for eugonadal patients with late onset hypogonadism symptoms.

The impact of Hounsfield unit-related variables on percutaneous nephrolithotomy outcomes.

We aimed to identify the association between Hounsfield Unit(HU)-related variables and percutaneous nephrolithotomy (PCNL) outcomes. We enrolled patients with single renal stones (1-3 cm) who underwent single-tract PCNL between January 2014 and October 2019. Demographics and stone characteristics were retrospectively reviewed. Preoperative computerized tomography (CT) and follow-up CT within at least 3 months after PCNL were included in this analysis. Stone-free status was defined as residual stone measuring ≤ 2 mm within 3 months postoperatively. HU and cross-sectional area (CSA) were measured using the free-draw technique. We analyzed HU-related variables using logistic regression model for outcomes. Altogether, 188 out of 683 patients met the inclusion criteria. The stone-free rate (SFR) was 79.2%. There were no significant differences in age, sex, BMI, ASA class, laterality, pre-op shockwave lithotripsy, stone size, stone burden, skin-to-stone distance, and HU between the stone-free and remnant groups. CSA and HU/CSA in the stone-free and remnant groups were 94.5 ± 46.1 and 128.3 ± 98.5 (p = 0.043) and 10.1 ± 5.6 and 7.3 ± 3.4 (p = 0.001), respectively. Multivariate logistic regression analysis revealed that pelvis, ureteropelvic junction stones, and HU/CSA were independent predictors of SFR. HU did not affect PCNL outcomes. We believe that HU/CSA could be used for determining stone treatment plans and predicting outcomes.

Prediction of Bacterial sRNAs Using Sequence-Derived Features and Machine Learning.

Small ribonucleic acid (sRNA) sequences are 50-500 nucleotide long, noncoding RNA (ncRNA) sequences that play an important role in regulating transcription and translation within a bacterial cell. As such, identifying sRNA sequences within an organism's genome is essential to understand the impact of the RNA molecules on cellular processes. Recently, numerous machine learning models have been applied to predict sRNAs within bacterial genomes. In this study, we considered the sRNA prediction as an imbalanced binary classification problem to distinguish minor positive sRNAs from major negative ones within imbalanced data and then performed a comparative study with six learning algorithms and seven assessment metrics. First, we collected numerical feature groups extracted from known sRNAs previously identified in Salmonella typhimurium LT2 (SLT2) and Escherichia coli K12 (E. coli K12) genomes. Second, as a preliminary study, we characterized the sRNA-size distribution with the conformity test for Benford's law. Third, we applied six traditional classification algorithms to sRNA features and assessed classification performance with seven metrics, varying positive-to-negative instance ratios, and utilizing stratified 10-fold cross-validation. We revisited important individual features and feature groups and found that classification with combined features perform better than with either an individual feature or a single feature group in terms of Area Under Precision-Recall curve (AUPR). We reconfirmed that AUPR properly measures classification performance on imbalanced data with varying imbalance ratios, which is consistent with previous studies on classification metrics for imbalanced data. Overall, eXtreme Gradient Boosting (XGBoost), even without exploiting optimal hyperparameter values, performed better than the other five algorithms with specific optimal parameter settings. As a future work, we plan to extend XGBoost further to a large amount of published sRNAs in bacterial genomes and compare its classification performance with recent machine learning models' performance.

Novel dapagliflozin di-L-proline cocrystal-loaded tablet: preparation, physicochemical characterization, and pharmacokinetics in beagle dogs and mini-pigs.

Dapagliflozin base and a commercial dapagliflozin propanediol hydrate cocrystal (DPF-PDHC) were highly hygroscopic and thermally unstable. In this study, to address this limitation, we prepared a novel dapagliflozin di-L-proline cocrystal (DPF-LPC) and evaluated its physicochemical characterization compared with DPF-PDHC. After the preparation of the DPF-LPC-loaded tablet, its dissolution, stability and bioequivalence in beagle dogs and mini-pigs were assessed. DPF-LPC was well prepared with a dapagliflozin base and L-proline in a molar ratio of 1:2. Similar to DPF-PDHC, DPF-LPC was highly lipophilic and crystalline in nature. However, these two cocrystals exhibited different melting points and crystalline structures, indicating their different cocrystal forms. Moreover, DPF-LPC exhibited less hygroscopicity and lower water content than DPF-PDHC. The DPF-LPC-loaded tablet composed of DPF-LPC, Comprecel M102, lactose monohydrate, crospovidone, magnesium stearate, and Opadry (coating) at a weight ratio of 15.6:104.4:100.0:8.0:2.0:7.0, was dissolution-equivalent to the commercial tablet. Moreover, it provided lower impurities than the commercial tablet, indicating its better stability. In the two animals, there were no significant differences in the plasma concentrations, AUC, Cmax, and Tmax values, suggesting that they were bioequivalent. Therefore, the novel DPF-LPC-loaded tablet with excellent stability and bioequivalence may be used as a potential alternative to the commercial DPF-PDHC-loaded tablet.

Comparison of CT volumetry versus nuclear renography for predicting remaining kidney function after uninephrectomy in living kidney donors.

Computed tomography (CT) and nuclear renography are used to determine kidney procurement in living kidney donors (LKDs). The present study investigated which modality better predicts kidney function after donation. This study included 835 LKDs and they were divided into two subgroups based on whether the left-right dominance of kidney volume was concordant with kidney function (concordant group) or not (discordant group). The predictive value for post-donation kidney function between the two imaging modalities was compared at 1 month, 6 months, and > 1 year in total cohort, concordant, and discordant groups. Split kidney function (SKF) measured by both modalities showed significant correlation with each other at baseline. SKFs of remaining kidney measured using both modalities before donation showed significant correlation with eGFR (estimated glomerular filtration rate) after donation in the total cohort group and two subgroups, respectively. CT volumetry was superior to nuclear renography for predicting post-donation kidney function in the total cohort group and both subgroups. In the discordant subgroup, a higher tendency of kidney function recovery was observed when kidney procurement was determined based on CT volumetry. In conclusion, CT volumetry is preferred when determining procurement strategy especially when discordance is found between the two imaging modalities.