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Background: The main pathophysiologic conditions of erectile dysfunction (ED) after radical prostatectomy are considered to be corporal fibrosis and apoptosis induced by cavernosal nerve (CN) injury. Objectives: In a rat model of CN crush injury (CNCI), we investigated whether combination treatment with JNK inhibitor (JNKi), SP600125, and HDAC inhibitor (HDACi), suberoylanilide‐hydroxamic‐7 acid (SAHA), for 2 weeks after CNCI would restore erectile function by suppressing fibrosis and apoptosis through normalization of JNK and HDAC pathways. Materials and methods: Seventy 12‐week‐old rats were randomly divided into five groups: Sham surgery, CNCI alone, CNCI treated with daily intraperitoneal injection of 10 mg/kg JNKi, CNCI treated with daily oral administration of 25.0 mg/kg HDACi, and CNCI daily treated with a combination. Two weeks after CNCI, we investigated the erectile response to electrostimulation and conducted histological staining, caspase‐3 activity assay, and western blot analysis. Results: CNCI alone resulted in significantly reduced intracavernosal pressure/mean arterial pressure (MAP) and area under the curve/MAP, decreased smooth muscle (SM)/collagen ratio and SM content, higher caspase‐3 activity, and increased protein levels of total HDAC3, transforming growth factor (TGF)‐β, fibronectin, and c‐Jun phosphorylation, compared with the Sham surgery. The CNCI groups exposed to JNKi, HDACi or both showed improvements in erectile‐responses and SM/collagen ratio, compared to the CNCI alone. The combined treatment showed additional improvement in erectile responses at 1.0V stimulation and in SM/collagen ratio compared to the single agent treatment. SM content, caspase‐3 activity, and c‐Jun phosphorylation improved in the two CNCI groups exposed to JNKi. The two CNCI groups exposed to HDACi showed normalization of protein levels of HDAC3, fibronectin, and TGF‐β. Discussion and conclusions: The combined administration of JNKi and HDACi during the acute phase after CNCI in rats can preserve ED by suppressing cavernosal fibrosis and apoptosis by normalizing the HDAC/TGF‐β and JNK pathways. [ABSTRACT FROM AUTHOR]

Background: Cavernosal fibrosis, which is induced by cavernosal nerve (CN) injury and progresses with time, is the main cause of cavernosal veno‐occlusive dysfunction (CVOD) after radical prostatectomy. Objectives: To determine whether daily oral administration of suberoylanilide hydroxamic acid (SAHA; vorinostat) for 5‐weeks from the immediate post‐injury period after CN injury would rectify CVOD by suppressing cavernosal fibrosis and normalizing HDAC pathway in a rat model of CN crush injury (CNCI) and to compare the results with those obtained using chronic administration of PDE5‐inhibitors (a positive control). Methods: Fifty‐six 12‐week‐old rats were randomized into the four groups: sham surgery (S), CNCI (I), and CNCI treated with daily administration of 25.0 mg/kg SAHA (V) or 20.0 mg/kg udenafil (P). Group‐V and Group‐P received the respective treatment for 5‐weeks from the following day after CNCI. At 5 weeks after surgery, dynamic infusion cavernosometry (DIC), histological staining, and Western blot analysis were performed. Results: Group‐I had a significantly decreased papaverine response, higher maintenance rate or drop rate, lower smooth muscle (SM)/collagen ratio, decreased SM content, and increased protein expression of HDAC2, HDAC3, TGF‐β1, and collagen‐1, compared with Group‐S. The three DIC parameters in Group‐V and Group‐P significantly improved compared to those in Group‐I. Except for the maintenance rate, the improvement in papaverine response and drop rate in Group‐V was not significantly different from that in Group‐P. Group‐V and Group‐P showed the rectification of SM/collagen ratio and protein expression of TGF‐β1 or collagen‐1. SM content was improved in Group‐P, but not in Group‐V. Group‐V showed the normalization of protein expression of both HDAC2 and HDAC3, whereas protein expression of only HDAC2 was partially restored in Group‐P. Discussion: Treatment strategies targeting the HDAC pathway might be helpful to alleviate CVOD induced by CN injury. Conclusions: According to our data, chronic administration of SAHA improves post‐injury CVOD by suppressing cavernosal fibrosis via rectifying the HDAC/TGF‐β1 pathway in nerve‐injured rats, comparable to that with PDE5 inhibitors. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the impact of preoperative detrusor underactivity (DU) on serial treatment outcomes over the course of 5 years after photovaporization (PV) or holmium laser enucleation (HoLEP) in patients with benign prostatic hyperplasia (BPH), to compare its impact after PV vs HoLEP, and to identify predictors of long‐term lower urinary tract symptoms (LUTS) improvement. Materials and Methods: This study involved 245 patients with BPH who had complete 5‐year follow‐up data (PV using 120W‐HPS, n = 143, HoLEP, n = 102), grouped as follows: PV‐HPS‐DU(+), n = 114; PV‐HPS‐DU(−), n = 29; HoLEP‐DU(+), n = 56; and HoLEP‐DU(−), n = 46. Bladder contractility index (BCI) < 100 was regarded as DU. Serial treatment outcomes for the International Prostate Symptom Score (IPSS) questionnaire, uroflowmetry and serum PSA level at 6 months, and at 1, 2, 3, 4 and 5 years after surgery, were compared among the groups. LUTS improvement was defined as a reduction in total IPSS of ≥50% relative to baseline. Results: Improvement in total IPSS, quality of life (QoL) index and post‐void residual urine volume (PVR) in the PV‐HPS‐DU(+) and PV‐HPS‐DU(−) groups were maintained up to 5 years after PV, except for maximum urinary flow rate (Qmax) and bladder voiding efficiency. In the HoLEP‐DU(+) and HoLEP‐DU(−) groups, improvements in all outcome variables were maintained up to 5 years after HoLEP. Deteriorations in subtotal voiding symptom score, total IPSS and Qmax with time during the long‐term period after surgery were more pronounced in the PV‐HPS‐DU(+) and HoLEP‐DU(+) groups than in the PV‐HPS‐DU(−) and HoLEP‐DU(−) groups. Reductions in subtotal voiding symptom score, total IPSS, QoL index, and serum PSA were greater in the HoLEP‐DU(+) group than in the PV‐HPS‐DU(+) group throughout follow‐up. The type of surgery (HoLEP vs PV) and higher baseline BCI were independent predictors of LUTS improvement at 5 years after surgery. Conclusion: Generally, improvement of micturition symptoms, QoL and PVR in patients with DU appears to be maintained up to 5 years after PV or HoLEP. Deterioration of voiding symptoms and urinary flow rate at long‐term follow‐up visits after PV or HoLEP was more pronounced in patients with LUTS/BPH with DU than in those without DU. Patients with BPH with DU may benefit from more complete removal of prostatic adenoma by HoLEP and greater baseline bladder contractility in terms of micturition symptoms and QoL. [ABSTRACT FROM AUTHOR]

This study aimed to determine serial changes in self-assessed goal achievement (SAGA) and treatment satisfaction after HoLEP, to identify correlations between the two, and to compare them with results assessed by traditional outcome measures. For a total of 170 patients, outcomes were evaluated serially at postoperative 1-, 3-, 6-, and 12-months using IPSS, OABSS, SAGA questionnaires and uroflowmetry. The SAGA questionnaire consisted of five questions including one open-ended question (self-assessed goals and degree of SAGA) and another question regarding treatment satisfaction. The number of self-assessed treatment goals was two or more in 74.1% of the patients. Most common treatment goal was relief from straining/hesitancy, followed by increased daytime frequency, nocturia and feeling of incomplete emptying. Degree of achievement for the first or second goal and treatment satisfaction tended to increase with time throughout the follow-up period. Patients with the greatest treatment satisfaction scores showed greater improvement by traditional outcome parameters including quality of life (QOL) index, total OABSS, maximum flow rate (Qmax), post-void residual urine volume (PVR) and bladder voiding efficiency (BVE) compared to those without treatment satisfaction. After adjusting for other influential variables, the improvements in subjective outcome parameters including total IPSS, QOL index and total OABSS were significantly associated with treatment satisfaction, but improvements in objective outcome parameters including Qmax, PVR and BVE were not. In addition, the degree of SAGA for the first goal or second goal was more predictive in determining treatment satisfaction than the traditional outcome measures. In conclusion, treatment goals of patients with lower urinary tract symptoms (LUTS)/BPH vary from individual to individual. The degree of SAGA and treatment satisfaction for HoLEP tends to increase with time throughout the follow-up period. Compared to the traditional outcome measures, the degree of goal achievement can be more predictive when assessing patient-centered outcomes such as treatment satisfaction. [ABSTRACT FROM AUTHOR]

Objective: To investigate patient perception of ejaculatory volume reduction after Holmium laser enucleation of the prostate (HoLEP).Materials and Methods: A total of 192 patients were included in the analysis. All patients completed 6 self-developed, nonvalidated questionnaires. The questionnaires were composed of questions involving overall satisfaction, voiding symptom change, current experience of sexual intercourse, ejaculatory volume change, change of orgasmic intensity, and the patient's perception of postoperative ejaculatory volume reduction. Questionnaire results and clinical parameters were analyzed, and subgroup analysis according to the patient's perception was also performed.Results: The median patient age was 66.0 years, and the mean total prostate volume and enucleated prostate volume was 61.9 ± 24.1 mL and 22.4 ± 14.0 mL, respectively. Among 192 patients, 91 patients had had sexual intercourse within the past 3 months. Ejaculatory volume changes after HoLEP were as follows: "total loss" (76.9%), "decreased" (18.7%), and "no change"(4.4%). Among the 87 patients who reported ejaculatory volume reduction, their perceptions of this issue were as follows: "feels better"(2.3%), "not a problem" (16.1%), "disappointed, but able to tolerate, owing to improvement of voiding symptoms" (73.6%), and "dissatisfied and want to reverse the situation"(8.0%). Decreased orgasmic intensity was present in 48 (52.8%) patients. There were significantly more patients who reported decreased orgasmic intensity among those who wanted to reverse the situation compared with the others (P = .027).Conclusion: Our study showed that most of the patients reported ejaculatory volume reduction and more than half of the patients reported decreased orgasmic intensity after HoLEP. We also found that patients' perceptions of ejaculatory volume reduction and orgasmic intensity were closely related to each other. [ABSTRACT FROM AUTHOR]

HIV primary resistance, drug resistance in treatment-naïve patients, is an emerging public health issue. The prevalence of HIV primary resistance mutations down to the level of 1% minor variants was investigated using ultradeep pyrosequencing (UDPS) in HIV-positive Korean blood donors and in treatment naïve chronic patients for the comparison. The entire pol region was sequenced from 25 HIV-positive blood donors, and 18 treatment-naïve chronic HIV patients. UDPS was successful in 19 blood donors and 18 chronic patients. In total, 1,011,338 sequence reads were aligned, and 28,093 sequence reads were aligned on average per sample. The prevalence of HIV primary resistance mutations in the HIV-positive blood donors and chronic HIV patients were 63.2% and 44.4% according to UDPS, respectively. Protease inhibitor (PI) drugs demonstrated different patterns in HIV-positive blood donors and chronic HIV patients, whereas non-nucleoside reverse transcriptase inhibitors (NNRTI), nucleoside reverse transcriptase inhibitors (NRTI), and integrase inhibitor (INI) drugs showed similar patterns between the two groups. Higher level of primary resistance prevalence was observed mainly because UDPS method could detect mutations in minor variants with 1–10% frequency. The higher resistance prevalence was observed in HIV-positive blood donors than in chronic patients. Considering that treatments for HIV-infected patients were recently amended to start at an earlier stage, information about degree of drug resistance to each drug between the two groups would help to establish future policies, design additional clinical trials, assess HIV patient care in Korea. [ABSTRACT FROM AUTHOR]

Objective: To evaluate impacts of preoperative detrusor underactivity (DU) on outcomes of photoselective vaporization of the prostate (PVP) or holmium laser enucleation of the prostate (HoLEP) for benign prostatic hyperplasia, and to compare them between the two surgeries.Materials and Methods: A total of 1423 men, who underwent PVP (group A) or HoLEP (group B), were categorized into four groups: A1 (239 without DU), A2 (432 with DU), B1 (329 without DU), and B2 (423 with DU). DU was defined as bladder contractility index of <100. Outcomes were assessed at 1, 3, 6, and 12 months postoperatively using International Prostate Symptom Score (IPSS), uroflowmetry, and prostate-specific antigen. Successful outcome was defined as reductions by ≥50% of total IPSS at 12 months postoperatively.Results: In all four groups, almost all parameters of IPSS and uroflowmetry improved starting from 1 month. A1 or B1 had greater increases in maximum flow rate than A2 or B2. Decreases of total IPSS in A2 were less than in A1 starting from 1 month after PVP, whereas those in B2 were less than those in B1 as late as 12 months after HoLEP. B2 showed greater improvements in maximum flow rate, subtotal voiding symptom score, bladder voiding efficiency, and total IPSS than A2. In all patients, multivariate regression analysis revealed that the absence of DU, presence of bladder outlet obstruction, and higher baseline total IPSS were independent predictors of successful outcome after surgery, but the type of laser surgery (PVP vs HoLEP) was not.Conclusion: Our data suggest that micturition symptoms, maximum flow rate, bladder voiding efficiency, and quality of life improve starting from the early period after PVP or HoLEP, irrespective of DU. However, patients with DU may have less degree of improvement in micturition after PVP or HoLEP than those without DU. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the clinical and microbiological features in the patients with community-acquired acute bacterial prostatitis (CA-ABP), as well as factors that affect fluoroquinolone resistance. Methods: A retrospective analysis was performed of 209 patients hospitalized for antibiotic treatment of CA-ABP. We investigated patient age, body mass index, underlying diseases, recurrence, prostate-related factors and results of urine culture examination and antibiotic sensitivity tests. Results: Seventeen patients (8.1%) had fluoroquinolone-resistant bacterial colonies. When we divided the subjects into groups according to the fluoroquinolone resistance, the group with resistant bacteria was significantly older, had larger prostates and had greater residual urine volumes. Bacteria were identified in 127 of 209 patients (60.8%), and the most commonly cultured included Escherichia coli (43.5%). The sensitivity of the cultured bacteria to fluoroquinolones was high compared to trimethoprim/ sulfamethoxazole and gentamicin, but similar to cefotaxime. The bacteria were more sensitive to amikacin and imipenem than to fluoroquinolone. The multivariate analysis revealed that prostate volume ± 40 ml (p = 0.024) and residual urine volume >100 ml (p = 0.004) were independent predictive factors for fluoroquinolone resistance. Conclusions: Fluoroquinolone monotherapy might be an effective treatment in CA-ABP. However, combination antibiotic therapy is recommended in cases with prostate volume ± 40 ml or residual urine volume >100 ml, because fluoroquinolone resistance can occur [ABSTRACT FROM AUTHOR]

Objectives: To investigate the role of EphA2 in malignant cellular behavior in renal cell carcinoma (RCC) cells and whether FAK/RhoA signaling can act as downstream effectors of EphA2 on RCC cells. Methods: Expression of EphA2 protein in non-metastatic RCC (Caki-2 and A498), metastatic RCC cells (Caki-1 and ACHN), HEK-293 cells and prostate cancer cells (PC-3 and DU-145; positive controls of EphA2 expression) was evaluated by Western blot. Changes in mRNA or protein expression of EphA2, FAK or membrane-bound RhoA following EphA2, FAK or RhoA small interfering RNA (siRNA) transfection were determined by reverse transcription polymerase chain reaction or Western blot. The effect of siRNA treatment on cellular viability, apoptosis and invasion was analyzed by cell counting kit-8, Annexin-V and modified Matrigel-Boyden assays, respectively. Results: In all RCC cell lines, the expression of EphA2 protein was detectable at variable levels; however, in HEK-293 cells, EphA2 expression was very low. Treatment with EphA2 siRNA significantly reduced the expression of EphA2 mRNA and protein in all RCC cell lines. For non-metastatic RCC cells (Caki-2 and A498) but not metastatic RCC cells (Caki-1 and ACHN), cellular viability, invasiveness, resistance to apoptosis, expression of membrane-bound RhoA protein and FAK phosphorylation were significantly decreased in EphA2 siRNA-treated cells compared to the control. In non-metastatic RCC cells, FAK siRNA significantly attenuated the invasiveness, resistance to apoptosis, as well as expression of membrane-bound RhoA protein without changing protein expression of EphA2. RhoA siRNA significantly decreased the malignant cellular behavior and expression of membrane-bound RhoA protein without changing EphA2 protein expression or FAK phosphorylation. Conclusions: Our data provide the first functional evidence that the EphA2/FAK/RhoA signaling pathway plays a critical role in the malignant cellular behavior of RCC and appears to be functional particularly in the early stage of malignant progression of non-metastatic RCC. [ABSTRACT FROM AUTHOR]

Verification of new lot reagent’s suitability is necessary to ensure that results for patients’ samples are consistent before and after reagent lot changes. A typical procedure is to measure results of some patients’ samples along with quality control (QC) materials. In this study, the results of patients’ samples and QC materials in reagent lot changes were analysed. In addition, the opinion regarding QC target range adjustment along with reagent lot changes was proposed. Patients’ sample and QC material results of 360 reagent lot change events involving 61 analytes and eight instrument platforms were analysed. The between-lot differences for the patients’ samples (ΔP) and the QC materials (ΔQC) were tested by Mann–Whitney U tests. The size of the between-lot differences in the QC data was calculated as multiples of standard deviation (SD). The ΔP and ΔQC values only differed significantly in 7.8% of the reagent lot change events. This frequency was not affected by the assay principle or the QC material source. One SD was proposed for the cutoff for maintaining pre-existing target range after reagent lot change. While non-commutable QC material results were infrequent in the present study, our data confirmed that QC materials have limited usefulness when assessing new reagent lots. Also a 1 SD standard for establishing a new QC target range after reagent lot change event was proposed. [ABSTRACT FROM PUBLISHER]

Objectives: There is no consensus on the management plan for incidental prostate cancer (IPCa) after holmium laser enucleation of the prostate (HoLEP). This study aims to investigate the natural course of this disease and suggest appropriate treatment in real clinical practice. Methods: The medical records of a prospective cohort of patients with LUTS/BPH who underwent HoLEP between July 2008 and December 2020 at Seoul National University Hospital were retrospectively reviewed. Patients who underwent HoLEP for palliative purpose of prostate cancer control were excluded. The natural history of IPCa was assessed by the clinician in a descriptive manner for each treatment option. Results: Among 2630 patients, 141 (5.4%) were diagnosed with IPCa after HoLEP. Pathologic T stage and magnetic resonance imaging results were highly associated with the physician's primary treatment decision-making for IPCa. Active surveillance (AS) was performed in 80% of patients, of whom 90% underwent follow-up without intervention, while the remaining 10% underwent deferred active treatment with a median follow-up of 46.3 months due to International Society of Urological Pathology grade group upgrading or increasing core involvement percentage. Meanwhile, 20% of patients underwent immediate active treatment. With a median follow-up period of 88.3 months after treatment, only one of 25 patients had biochemical recurrence. Conclusions: The incidence of IPCa after HoLEP was 5.4%, and among these, approximately 20% proceeded with immediate definitive therapy and an additional 6% ultimately received definitive therapy within a median of 4 years of AS but showed excellent oncological outcomes. [ABSTRACT FROM AUTHOR]

Erectile dysfunction (ED) is often perceived by both patients and sexual partners as a serious problem that can jeopardize quality of life, psychosocial or emotional well-being, and the partnership in the long term. Since their introduction, oral phosphodiesterase type 5 inhibitors (PDE5Is) have been found to be highly effective and well tolerated, and are available as the first-line therapy for the treatment of ED. Udenafil is one of the selective PDE5Is made available in recent years for the treatment of ED. Udenafil has clinical properties of both relatively rapid onset and long duration of action due to its pharmacokinetic profile, thereby providing an additional treatment option for ED men to better suit individual needs. There is positive evidence that udenafil is effective and well tolerated in the treatment of ED of a broad spectrum of etiologies or severity. Udenafil is as effective in the treatment of diabetes mellitus-associated ED as other PDE5Is. Due to the clinical property of relatively long duration of action, udenafil may be another option in daily dosing treatment for ED, as suggested by its favorable efficacy and safety profile. Most adverse effects reported from clinical trials are mild or moderate in severity, without any serious adverse event, with headache and flushing being the most common. Also, the concomitant use of anti-hypertensive drugs or alpha-1-blockers does not significantly affect the efficacy and safety profile of udenafil. However, additional studies with larger cohorts including prospective, multicenter, comparative studies with patients of different ethnicities are needed to further validate the favorable findings of udenafil in the treatment of ED. [ABSTRACT FROM AUTHOR]

Background Work-up of post-transplant lymphoproliferative disorders ( PTLDs) often involves bone marrow ( BM) examinations. We evaluated 23 transplant patients with PTLDs to investigate incidence of BM involvement and associated morphologic changes as well as prognosis. Methods We retrospectively assessed BM findings of 23 transplant patients with PTLDs who had undergone BM staging at Seoul Asan Medical Center from 1994 to 2010. Results Four (17%) showed BM involvement of PTLDs, including two pathologically diagnosed with PTLD by liver and skin biopsy and two diagnosed by BM examination. PTLD subtypes in four patients were all monomorphic, with one each having plasma cell myeloma, diffuse large B cell lymphoma, monomorphic B cell lineage, and monomorphic T-cell lineage. Epstein- Barr virus ( EBV) in situ hybridization showed 11 of 23 (47.8%) patients were EBV positive, including two patients with BM involvement, one each with plasma cell myeloma and monomorphic T-cell lineage. Epstein-Barr virus infection was observed in nine of 19 patients (39.1%) without BM involvement or morphologic abnormalities. Mortality rate was higher in patients with than without BM involvement (p = 0.050). Conclusion High incidence of BM involvement in patients with PTLD and high mortality rates of these patients suggest BM examination study may be important in diagnosis and staging work-up of PTLD. [ABSTRACT FROM AUTHOR]

Background: New therapeutics targeting epidermal growth factor receptor (EGFR) have significantly improved tumor responses to therapy in non-small cell lung cancer (NSCLC) patients. Molecular testing for EGFR mutations informs important therapeutic decisions in clinical practice. In this study, we sought to validate the clinical relevance of sequencing-based EGFR mutation testing combined with cytological analysis using body fluid specimens. Methods: Two NSCLC cell lines were used in sensitivity analyses. In addition, we performed cytological analyses and directly sequencing of exons 18-21, for 32 specimens. The absence of EGFR mutations determined by direct sequencing in 14 specimens was confirmed by real-time PCR. Changes made to patients' therapeutic strategies after reports of EGFR mutation status were investigated by querying electronic medical records. Results: Sensitivity studies showed that detection of in-frame deletions in exon 19 and point mutations in exon 21 was possible in specimens containing 10% and 5% mutant DNA, respectively. In clinical practice, EGFR mutations were detected in 18 of 32 specimens (56.3%). Twelve patients with EGFR mutations detected by direct sequencing were started on treatment with EGFR tyrosine kinase inhibitor (TKI) after reports of EGFR mutation. EGFR-TKI therapy was discontinued for two patients with TKI-resistant T790M mutation. The results of real-time PCR were consistent with those of direct sequencing in 13 of 14 specimens (92.9%) in which no mutation was detected by direct sequencing. Conclusions: Combined direct sequencing and cytological analysis of body fluid specimen might be clinically useful and sensitive test for the detection of EGFR mutations in NSCLC patients. [ABSTRACT FROM AUTHOR]

Abstract: Indole-3-carbinol (I3C) has anti-tumor effects in various cancer cell lines. However, the anti-tumor effect of I3C on human lung cancers has been rarely reported. We investigated the anti-tumor effects and its mechanism of I3C on human lung carcinoma A549 cell line. Treatment of the A549 cells with I3C significantly reduced cell proliferation, increased formations of fragmented DNA and apoptotic body, and induced cell cycle arrest at G0/G1 phase. I3C increased not only the protein levels of cyclin D1, phosphorylated p53, and p21 but also the expression of Fas mRNA. Cleavage of caspase-9, -8, -3 and PARP also was increased by I3C. Treatment with wortmannin significantly suppressed both I3C-induced Ser15 phosphorylation and accumulation of p53 protein. The inhibition of caspase-8 by z-IETD-FMK significantly decreased cleavage of procaspase-8,-3 and PARP in I3C-treated A549 cells. Taken together, these results demonstrate that I3C induces cell cycle arrest at G0/G1 through the activation of p-p53 at Ser 15 and induces caspase-8 mediated apoptosis via the Fas death receptor. This molecular mechanism for apoptotic effect of I3C on A549 lung carcinoma cells may be a first report and suggest that I3C may be a preventive and therapeutic agent against lung cancer. [Copyright &y& Elsevier]

Peroxisome proliferator-activated receptors (PPARs) are transcription factor which directly modulate gene expression by binding to specific agonists. It has been reported that PPARα controls lipid metabolism, inflammation, and atherosclerosis. PPARα activation by PPARα agonist can ultimately reduce the progression of atherosclerosis and decrease the incidence of coronary heart disease. In this study, we optimized enzyme-linked immunosorbent assay (ELISA) systems in order to screen putative PPARα agonists. These methods are based on the activation mechanism of PPARα where the ligand binding to PPARα induces the interaction of the receptor with transcriptional co-activators. Among co-activators such as SRC-1, TIF-2, and p300, although ligand-unbound PPARα had more strong binding with p300 at a lower concentrations of PPARα, ligand-bound PPARα had more specific and strong binding with SRC-1. We optimized and developed a novel and useful ELISA system to screen PPARα agonists. Wy14,643 and linoleic acid, the well-known PPARα ligands, increased the binding between PPARα and co-activators in a ligand dose-dependent manner. In this ELISA method to screen PPARα ligands, the use of specific anti-PPARα N-terminus antibody, full-length recombinant protein of human PPARα but not ligand-binding domain (LBD) of human PPARα, and his-tagged PPARα recombinant proteins but not GST-fused PPARα recombinant proteins is the critical factors. Development of this screening system may be useful in the discovery of PPARα ligands from various candidates such as chemical library and phytochemicals. [ABSTRACT FROM AUTHOR]

Objectives: To determine the efficacy of a diuretic agent, hydrochlorothiazide, as second-line therapy after failed α-blocker therapy for men with nocturia. Methods: The study inclusion criteria were a <25% reduction in nocturia using the International Prostate Symptom Score question 7, a <25% reduction in nocturia using the frequency-volume chart, and/or nocturia ≥2/night (according to the frequency-volume chart) after 4 weeks of terazosin therapy. A total of 72 patients were entered into the study and treated with 25 mg of hydrochlorothiazide and 4 mg of terazosin once daily for 4 weeks. Of the 72 eligible men, 53 completed the study. Results: No serious side effects occurred among the treated patients. Using the International Prostate Symptom Score, a reduction of ≥50%, 25%-49%, 0%-24% and an increase in nocturia was observed in 7, 7, 31, and 8 patients, respectively. Using the frequency-volume chart, 17 patients reported reduced nocturia by more than one half, 5 reported a reduction of 25%-49%, and 31 reported no response to treatment or an increase in nocturia. At baseline, all except for 1 patient had nocturnal polyuria (nocturnal polyuria index >33%), and, after the combination therapy, the nocturnal polyuria had resolved in 6 (11.5%) of the 52 patients with nocturnal polyuria at baseline. Conclusions: Hydrochlorothiazide combined with terazosin was safe and effective in reducing nocturnal frequency for some men after failed terazosin therapy. Our findings suggest that the use of a diuretic agent, such as hydrochlorothiazide, might be a reasonable second-line treatment option for these patients, especially for those with nocturnal polyuria. [Copyright &y& Elsevier]

Abstract: Epiregulin belongs to the epidermal growth factor family, binds to the epidermal growth factor receptor, and its expression is upregulated in various cancer cells, but the regulatory mechanism is unclear. We investigated the regulatory mechanism of epiregulin expression in Ki-ras-transformed cancer cells. In 267B1/Ki-ras cells, the RAF/MEK/ERK pathway was constitutively activated, epiregulin was up-regulated, and the expression and phosphorylation of Ets-1 were augmented. The inhibition of ERK by PD98059 decreased epiregulin and Ets-1 expression and suppressed the growth of 267B1/Ki-ras cells. A chromatin immunoprecipitation assay demonstrated that Ets-1 was bound to human epiregulin promoter, and this binding was abolished by PD98059. Silencing of Ets-1 by RNA interference decreased cellular epiregulin transcript expression. We suggest that the Ki-ras mutation in 267B1 prostate cells constitutively activates the RAF/MEK/ERK pathway and induces the activation of the Ets-1 transcription factor, ultimately leading to the increased expression of epiregulin. [Copyright &y& Elsevier]

Abstract: Peroxisome proliferator-activated receptors (PPARs) are transcription factors that belong to the nuclear receptor superfamily directly modulating gene expression by binding to specific ligands. Recently, it has been reported that PPARδ ligands play an essential role in improvement of metabolic disorders and skin disorders. We introduce an enzyme-linked immunosorbent assay (ELISA) to screen new PPARδ ligands. This method is based on the activation mechanism of PPARδ where the ligand binding to PPARδ induces the interaction of the receptor with transcriptional co-activators. We optimized a simple ELISA method for screening PPARδ ligands. Among co-activators such as SRC-1, TIF-2, and p300, PPARδ had more strong binding with SRC-1 in an ELISA system. GW501516 and linoleic acid, the well-known ligands of PPARδ, increased the binding between PPARδ and co-activators in a ligand dose-dependent manner. The recruitment of co-activator SRC-1 was also more effective than those of TIF-2 and p300. We optimized and developed a novel and useful ELISA system for the mass screening of PPARδ ligands. This screening system may be useful in the development of drugs for metabolic disorders and skin disorders. [Copyright &y& Elsevier]

Abstract: Based on the binding between peroxisome proliferators-activated receptor γ (PPARγ) and steroid receptor co-activator-1 (SRC-1), an enzyme-linked immunosorbent assay (ELISA) was used to screen new PPARγ ligands from various benzylidinethiazole derivatives, which have anti-inflammatory activity. Among those derivatives, 5-(3,5-di-tert-butyl-4-hydroxybenzylidene) thiazolidine-2,4-dione (BTZD) increased the binding between PPARγ and SRC-1. BTZD was found to induce adipogenesis and PPARγ trans-activation in 3T3-L1 pre-adipocyte, and increased the binding between PPARγ and SRC-1 in in vitro binding assay and complex consisting of PPARγ and SRC-1 in the co-immunoprecipitaion. Chromatin immunoprecipitation (ChIP) analysis revealed that BTZD induced the binding of PPARγ–SRC-1 complex to PPAR response element (PPRE) in the same pattern of other PPARγ ligand. From these studies, we have identified and studied the function of a new PPARγ ligand, BTZD. We suggest that BTZD can be used as a modulator of PPARγ. This study applying ELISA and ChIP assay can offer new methods to screen PPARγ ligand and understand the effects of PPARγ ligands on inflammation. [Copyright &y& Elsevier]

Abstract: Peroxisome proliferator-activated receptors (PPARs) are transcription factors that directly modulate gene expression by binding to specific ligands. It has been established that PPARγ ligands play an essential role in obesity, diabetes, and inflammation. Recently, a great deal of research has focused on the screening of PPARγ ligands. In this study, both a human peroxisome proliferator-activated receptors γ2 (PPARγ2) recombinant protein and a specific monoclonal antibody against PPARγ2 were produced in order to screen PPARγ ligands. Analysis of deletion mutants revealed that monoclonal anti-PPARγ antibody Pγ48.34A possesses an antigenic determinant in the N-terminal region (31–84 a.a) of human PPARγ2. The results of Western blot testing revealed that Pγ48.34A recognized both glutathione S-transferase (GST)- and his-tagged human and mouse PPARγ recombinant proteins and also identified PPARγ in adipocytes and mouse tissues. Compared to some commercially available antibodies, this antibody does not bind with skimmed milk or BSA and exhibits a higher degree of specificity. An in vitro binding assay revealed that PPARγ2 was bound to steroid receptor coactivator-1 (SRC-1) in a dose–responsive manner in the presence of indomethacin, and Pr48.34A was able to detect PPARγ in a complex consisting of PPARγ and SRC-1. Using Pγ48.34A antibody, an enzyme-linked immunosorbent assay (ELISA) system based on the binding between fPPARγ2 and SRC-1 has been optimized to screen new PPARγ ligands. This new antibody, Pγ48.34A, exhibits higher degrees of both specificity and sensitivity against PPARγ than do other commercial anti-PPARγ antibody, and may constitute a profound contribution to the screening of PPARγ ligands as well as the functional study of PPARγ. [Copyright &y& Elsevier]

Background: Periprosthetic joint infection (PJI) is one of the most serious and debilitating complications that can occur after total joint arthroplasty. Therefore, early diagnosis and appropriate treatment are important for a good prognosis. Recently, molecular diagnostic methods have been widely used to detect the causative microorganisms of PJI sensitively and rapidly. The Multiplex Loop-Mediated Isothermal Amplification (LAMP) method eliminates the complex temperature cycling and delays caused by temperature transitions seen in polymerase chain reaction (PCR) methods, making it faster and easier to perform compared to PCR-based assays. Therefore, this study developed a multiplex LAMP assay for diagnosing bacterial PJI using LAMP technology and evaluated its analytical and clinical performance. Methods: We developed a multiplex LAMP assay for the detection of five bacteria: Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus agalactiae, Pseudomonas aeruginosa, and Escherichia coli, frequently observed to be the causative agents of PJI. The method of analytical sensitivity and cross-reactivity were determined by spiking standard strains into the joint synovial fluid. The analytical sensitivity of the multiplex LAMP assay was compared with that of a quantitative real-time PCR (qPCR) assay. Clinical performance was evaluated using 20 joint synovial fluid samples collected from patients suspected of having bacterial PJI. Results: The analytical sensitivity of the gram-positive bacterial multiplex LAMP assay and qPCR were 105/104 CFU/mL, 103/103 CFU/mL, and 105/104 CFU/mL against S. agalactiae, S. epidermidis, and S. aureus, respectively. For P. aeruginosa and E. coli, the analytical sensitivity of the multiplex LAMP and qPCR assays were 105/104 and 106/104 CFU/mL, respectively. The multiplex LAMP assay detects target bacteria without cross-reacting with other bacteria, and exhibited 100% sensitivity and specificity in clinical performance evaluation. Conclusions: This multiplex LAMP assay can rapidly detect five high-prevalence bacterial species causing bacterial PJI, with excellent sensitivity and specificity, in less than 1 h, and it may be useful for the early diagnosis of PJI. [ABSTRACT FROM AUTHOR]

Introduction: The objectives of the study were to examine the opinions of urology specialists on whether there are actual differences in efficacy among α1-blockers and to identify the factors that should be considered when prescribing these medications according to age. Methods: We surveyed 50 South Korean urology specialists with over 3 years of clinical experience in secondary or tertiary hospitals in July-August 2021. The survey covered urologists' demographics, awareness of α1-blocker prescription differences, and key factors in α1-blocker selection based on LUTS severity and patient age. Results: Overall, 82% of the respondents believed that there were differences in the efficacy of α1-blockers in actual practice according to age. Over 90% of the respondents agreed on the need for head-to-head comparison studies to compare the effects of different α1-blockers. Regardless of the severity of LUTS, urologists prioritize cardiovascular side effects when prescribing α1-blockers to patients aged ≥70 years. Further, 19% of the urologists prioritized ejaculatory side effects for mild-to-moderate LUTS and 9% for severe LUTS (p < 0.001). Conclusions: This study shows that head-to-head studies comparing the efficacy of different α1-blockers are highly valuable for the real-world clinical application of α1-blockers. Notably, urologists prioritize cardiovascular and ejaculatory side effects in older and younger patients while prescribing α1-blockers, respectively. [ABSTRACT FROM AUTHOR]

To investigate the significance of detrusor muscle thickness (DMT) to bladder wall thickness (BWT) ratio as a detrusor-sarcopenia and a consistently applicable factor for noninvasive diagnosis of detrusor underactivity (DU). We prospectively performed a urodynamic study of 100 male with medical refractory lower-urinary-tract-symptoms during 2017–2019. The DMT, BWT and DMT/BWT ratio were measured by ultrasonography every 50 mL during bladder filling, and were analyzed for non-invasive diagnosis of DU and prediction of prostate surgery outcome with questionnaire and the maximum-flow-rate. Of the 94 patients, DU was urodynamically diagnosed in 24 (25.5%). The DMT/BWT ratio was maintained in all patients until the 50% of the maximum cystometric capacity (MCC), and then rapidly decreased. At 20% of the MCC, the DMT/BWT ratio was significantly lower in the DU group (44.0 ± 4.9% vs. 49.4 ± 6.7%, p = 0.008). The DMT/BWT ratio of less than 47.5% at 20% of the MCC showed the ideal accuracy for diagnosing DU (AUC = 0.763), and was a predictor of failure at 12 months after prostate surgery (OR 8.78, p = 0.024). A DMT/BWT ratio of less than 47.5% at 20% of the MCC is a consistently applicable factor for non-invasive diagnosis of DU and could also be considered detrusor-sarcopenia. [ABSTRACT FROM AUTHOR]

We evaluated the surgical margin status after radical prostatectomy according to sites positive for prostate cancer on standard 12-core transrectal ultrasound-guided prostate biopsy. Among patients who underwent radical prostatectomy at Boramae Medical Center, 520 patients with preoperative prostate-specific antigen (PSA) level < 20 ng/mL and locally confined prostate cancer on preoperative magnetic resonance imaging, treated with nerve-sparing radical prostatectomy, were included in the analysis. The surgical margin was positive for cancer in 166 (31.9% of the total) patients. The preoperative PSA level (9.3 vs. 8.0, ng/mL p = 0.001) and number of positive cores on 12-core prostate biopsy (4.1 vs. 3.4, p = 0.003) were significantly higher in patients with positive surgical margins. Moreover, the biopsy Gleason grade was higher in patients with positive surgical margins (p = 0.001). However, the pathologic Gleason grade and tumor volume were equivalent between the 2 groups. On multivariate analysis, the detection of prostate cancer on anterior lateral biopsy was associated with an increased rate of positive surgical margins (hazard ratio [HR]: 1.781, p = 0.008) after adjusting for other variables. Anterior lateral (HR: 1.919, p = 0.020), basal lateral (HR: 9.176, p < 0.001), basal medial (HR: 3.302, p = 0.031), and mid lateral (HR: 2.501, p = 0.044) biopsies were associated with positive apical, posterior, basal, and lateral surgical margins, respectively, after adjusting for other variables. The sites of prostate cancer on standard 12-core prostate biopsy could be useful for predicting surgical margin positivity after radical prostatectomy. In other words, clinicians should consider the sites of prostate cancer on prostate biopsy to reduce margin positivity after radical prostatectomy. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the feasibility of including patients with biopsy Gleason score (bGS) 3 + 4 prostate cancer in an active surveillance (AS) protocol. Methods: A total of 615 patients underwent a radical prostatectomy and satisfied the following requirements: prostate-specific antigen ≤10 ng/dL, clinical stage T1c or T2a, 2 or fewer positive biopsy cores, and bGS 6 or 3 + 4 prostate cancer. The patients were divided into two groups according to their bGS (bGS 6 group, n =534; bGS 3 + 4 group, n = 81). Results: The adverse pathological features were significantly higher in the bGS 3 + 4 group (16.7 vs. 49.4%, p< 0.001). Biochemical recurrence (BCR)-free survival was also significantly lower in this group (p < 0.001). In a multivariate analysis, clinical stage (odds ratio [OR] 2.026, p =0.007), maximum percentage of biopsy core involvement (OR 1.015, p = 0.014), and bGS (OR 1.913, p = 0.030) were independent risk factors for adverse pathological features. However, the bGS was the only variable to forecast BCR (hazard ratio 3.567, p < 0.001). Conclusions: A bGS 3 + 4 was the leading risk factor for a worse postoperative prognosis. Therefore, patients with a bGS 3 + 4 are not appropriate candidates for AS. [ABSTRACT FROM AUTHOR]

We investigated the prognosis of BCG induction-only treatment and non-complete response (CR) at the first 3-month evaluation and examined factors associated with CR. In total, 209 patients with moderate- and high-risk NMIBC who received BCG induction-only treatment between 2008 and 2020 were retrospectively analyzed. Recurrence-free survival (RFS) and progression-free survival (PFS) were assessed based on the initial NMIBC stage. PFS and associated factors of non-CR compared to CR were also assessed. Initial T1 high-grade (HG) (n = 93) had poorer RFS and PFS after BCG induction-only treatment than Ta low-grade (LG) (p = 0.029, p = 0.002). Non-CR (n = 37) had a different neutrophil-to-lymphocyte ratio (NLR) (2.81 ± 1.02 vs. 1.97 ± 0.92) and T staging from CR (p < 0.001, p = 0.008). T1HG recurrence was associated with a worse PFS compared to non-T1HG (13.7 months vs. 101.7 months, p < 0.001). There was no difference in PFS between T1HG and T1LG. T1 and NLR were predictors of response at 3 months in multivariable analysis (p = 0.004, p = 0.029). NLR was also found to be an associated factor with RFS and PFS of bladder cancer (p < 0.001, p < 0.001). BCG induction-only treatment was effective for high-risk TaLG but not for T1HG. T1HG recurrence at 3 months after BCG induction has a poor prognosis for bladder cancer. Preoperative NLR and T1 were predictors of non-CR, and NLR was also associated with the long-term prognosis of bladder cancer. [ABSTRACT FROM AUTHOR]

Introduction: We assessed the effects of exercise on the physical function and health quality of life (hQoL) in prostate cancer patients underwent androgen deprivation therapy (ADT). Additionally, the effects of high-intensity interval training (HIIT) on the physical function and hQoL in these patients were compared with those of moderate-intensity continuous training (MICT). Methods: Seventeen prostate cancer patients who underwent ADT were prospectively allocated to either HIIT (n = 9) or MICT (n = 8). In these patients, physical function and hQoL were measured before and after 12 weeks of exercise and 3–6 months after the exercise program, respectively. Results: Although the whole-body total mass significantly increased after the exercise program, it was equivalent regardless of the exercise methods. After the exercise program, muscle strength and endurance improved and tended to be maintained until 3–6 months later. Improvement in muscle endurance was more prominent after HIIT, and that in muscle strength was more prominent after MICT. Performance in the senior fitness test improved after the exercise program, and HIIT was more effective for lower and upper muscle endurance and flexibility, although MICT was more effective for the others. The hQoL significantly improved 3–6 months after the exercise program. Conclusion: The 12-week exercise program has a positive effect on the physical function and hQoL in prostate cancer patients who underwent ADT. In these patients, compared with MICT, HIIT may be a better option for improving muscle endurance, which is thought to be significant for preventing falls and fractures in elderly patients. [ABSTRACT FROM AUTHOR]

Background Structural alterations of the penis, including cavernosal apoptosis and fibrosis, induce venous leakage into the corpus cavernosum or cavernosal veno-occlusive dysfunction, a key pathophysiology associated with erectile dysfunction after radical prostatectomy. We hypothesized that the effect of JNK inhibitors on reducing apoptosis and hepatocyte growth factor (HGF) on inducing tissue regeneration could be another treatment mechanism of erectile dysfunction after radical prostatectomy. Aim To investigate whether JNK inhibition combined with intracavernosal administration of HGF can completely preserve cavernosal veno-occlusive function (CVOF) in a rat model of erectile dysfunction induced via bilateral cavernosal nerve crush injury (CNCI). Methods A total of 42 male Sprague-Dawley rats were randomly assigned to sham control (group S), CNCI (group I), and CNCI treated with a combination of JNK inhibitor and HGF (group J + H) for 5 weeks after surgery. Outcomes Rats in each group were evaluated via dynamic infusion cavernosometry (DIC), caspase-3 activity assay, Masson trichrome staining, immunohistochemical staining of α-smooth muscle actin, and immunoblotting at 5 weeks after surgery. Results Regarding CVOF, group I showed decreased papaverine response, increased maintenance, and drop rates of DIC when compared with group S. Group J + H showed significant improvement in the 3 DIC parameters vs group I. No differences in the 3 DIC parameters were found between group J + H and group S. Regarding the structural integrity of the corpus cavernosum, group I showed increased caspase-3 activity, decreased smooth muscle (SM):collagen ratio, decreased SM content, decreased protein expression of PECAM-1, and decreased phosphorylation of c-Jun and c-Met. Group J + H showed significant attenuation in histologic and molecular derangement as compared with group I. There were no differences in caspase-3 activity, SM content, SM:collagen ratio, PECAM-1 protein expression, c-Jun phosphorylation, and c-Met phosphorylation between groups J + H and S. Clinical Implications Our results suggest that antiapoptotic and regenerative therapy for the corpus cavernosum is a potential mechanism of penile rehabilitation after radical prostatectomy. Strengths and Limitations This study provides evidence that combination treatment of JNK inhibitor and HGF preserves erectile function by restoring corporal SM and endothelium. However, additional human studies are needed to confirm the clinical effect. Conclusion Chronic treatment with JNK inhibitor and HGF may preserve CVOF to levels comparable to sham control by preserving the structural integrity of the corpus cavernosum and so represents a potential therapeutic option for preventing the development of cavernosal veno-occlusive dysfunction. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the practicality of percent body fat (PBF), calculated using bioelectrical impedance analysis (BIA), in predicting benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS). Methods: This study included 844 men who underwent medical checkups at our institution between 2014 and 2022. Demographic characteristics, serum PSA levels, and prostate volume were collected using TRUS. BPH was defined as a prostate volume ≥ 30 cc. Subjects were divided into two groups according to their quartiles of PBF: the normal PBF group (first to third quartile; PBF < 27.9%) and the high PBF group (fourth quartile; PBF ≥ 27.9%). Characteristics between the groups were compared using the chi-square test and Student's t-test. Multivariate logistic regression analysis was performed to evaluate risk factors for BPH and severe LUTS. Results: The prostate volume (25.21 ± 8.4 vs 27.30 ± 9.0, p = 0.005) and percentage of BPH (22.9% vs. 32.1%, p = 0.007) were greater in the high PBF group. After multivariate analysis, old age (OR = 1.066, p < 0.001), higher appendicular skeletal muscle mass index (ASMI) (OR = 1.544, p = 0.001), and PBF ≥ 27.9% (OR = 1.455, p = 0.037) were risk factors for BPH. Larger prostate volume (OR = 1.035, p = 0.002) and PBF ≥ 27.9% (OR = 1.715, p = 0.025) were risk factors for severe LUTS. However, a greater ASMI had a protective effect against severe LUTS (OR = 0.654, p = 0.011). Conclusions: This study shows that PBF and ASMI are useful for predicting BPH/LUTS. We suggest that lowering PBF to the normal range in a population with high PBF might prevent BPH, while lowering PBF and maintaining adequate ASMI could lower LUTS. [ABSTRACT FROM AUTHOR]

Objective. To investigate the impact of pathologic upgrading of Gleason score (GS) 7 prostate cancer on the risk of the biochemical recurrence. Materials and Methods. A total of 1678 patients with postoperative GS 7 prostate cancer without lymph node metastasis were reviewed retrospectively. The patients were categorized into four groups depending on pathologic upgrading: upgraded GS 3+4, nonupgraded GS 3+4, upgraded GS 4+3, and nonupgraded GS 4+3. Kaplan-Meier multivariate model was created. Results. The mean age was significantly higher in the nonupgraded GS 4+3 group than in other groups, whereas the mean prostate-specific antigen (PSA) level was lower in the upgraded GS 3+4 group. Pathologic findings, such as extracapsular extension, seminal vesical invasion, and the surgical margin rate, were different from each other. Five-year biochemical recurrence-free survival rate was 85%, 73%, 69%, and 60% in upgraded GS 3+4, nonupgraded GS 3+4, upgraded GS 4+3, and nonupgraded GS 4+3 group, respectively. There was significant difference between the nonupgraded 4+3 and upgraded 4+3 group, as well as between upgraded 3+4 and nonupgraded 3+4 group. However, the two middle patient groups, that is, the nonupgraded GS 3+4 group and the upgraded GS 4+3 group, did not show the statistical difference (Log-rank test, p value = 0.259). Conclusion. The information on pathologic upgrading in the biopsy reports of patients could help to provide more detailed analysis for the biochemical recurrence of GS 7 prostate cancer. [ABSTRACT FROM AUTHOR]

Objective: We investigated the surgical efficiency and cutoff criteria to determine whether retrograde intrarenal surgery (RIRS) or supine miniaturized percutaneous nephrolithotomy (MPCNL) is appropriate for managing renal stones with a mean size >10 mm. Materials and Methods: Data of a single session RIRS or supine MPCNL were collected in a prospective, observational study. Change point analysis with a cumulative sum of ordered value of fragmentation efficiency and stone size was used to detect the point at which the statistical properties of a sequence of observation change. Results: A total of 310 RIRS and 66 MPCNL cases were included. No differences in patient characteristics were observed between the groups. Stone burden, fragmentation efficiency, stone distribution, and the presence of staghorn stones were higher in the MPCNL group than the RIRS group. Stone-free rates and complication rates were not different. The fragmentation efficiency increased to 40.4 mL/min, at which the stone size in the RIRS group was 19.1 mm. The efficiency was decreased after the peak point and became the same at the stone size 30 mm with 10 mm in RIRS group. The fragmentation efficiency in the MPCNL group continuously increased until the size of 35.1 mm. Conclusions: RIRS shows the highest efficiency at the maximal diameter of 19.1 mm and volume of 15,000 mm3. The acceptable level of stone size and volume for RIRS would be 30.0 mm and 27,000 mm3, respectively. However, MPCNL would be appropriate when surgeons want to get high surgical efficiency for renal stone >21.6 mm instead of RIRS. [ABSTRACT FROM AUTHOR]

Purpose: To investigate 5-year long-term postoperative efficacy in benign prostate hyperplasia (BPH) following 120-W GreenLight high-performance system photoselective vaporization of the prostate (HPS-PVP) Methods: This was a retrospective study of surgical outcomes in 159 men who underwent HPS-PVP and were followed over 60 months postoperatively. Definitions of treatment success were established based on the following three variables: international prostate symptom scores (IPSS), maximum flow rates (Qmax), and quality of life scores QoL). Logistic regression analyses were performed to determine predictors of the postoperative success. Results: Postoperative IPSS/QoL, Qmax and post-voided residual urine volume were significantly improved after HPS-PVP. Postoperative Prostate specific antigen and prostate volume were also well reduced and sustained for 5 years. The postoperative success rate was assessed as 82.1%, 80.8% and 76.1% for each 1-, 3-, and 5-year. Thirty-eight (23.9%) patients had immediate postoperative complications, which were managed successfully with nonsurgical methods. None required transfusions, two (1.2%) patients required endoscopic reoperation for postoperative voiding difficulty due to bladder neck contracture or urethral stricture, and five (3.1%) required HPS-PVP reoperation. Presence of diabetes, voiding symptom subscore, QoL, maximal cystometric capacity, and bladder outlet obstructive index were valuable preoperative parameters for predicting postoperative success. Conclusions: HPS-PVP is an effective, long-term treatment option for BPH, with sustained efficacy of 76.1% at 5-year follow up. Several preoperative parameters could help to predict the durable surgical improvements. [ABSTRACT FROM AUTHOR]

Objectives To analyze the feasibility of carrying out endoscopic combined intrarenal surgery with supine miniaturized percutaneous nephrolithotomy and retrograde intrarenal surgery for patients with bilateral stones in a single session. Methods The records of consecutive patients presenting with bilateral kidney stones who underwent endoscopic combined intrarenal surgery with miniaturized percutaneous nephrolithotomy (15-Fr miniaturized nephroscope) and retrograde intrarenal surgery on one side, and retrograde intrarenal surgery on the contralateral side were prospectively collected and analyzed. After the miniaturized percutaneous nephrolithotomy procedure, flexible uretero-renoscopy was carried out for active removal of the stone fragments. Subsequently, retrograde intrarenal surgery was carried out on the contralateral side. Results Overall, 26 patients were included in the analysis. The stone-free rate of the initial endoscopic combined intrarenal surgery side was 76.9% (20/26), and the stone-free rate of the contralateral retrograde intrarenal surgery side was 92.3% (24/26). Complications occurred in two patients (postoperative bleeding and urinary tract infection); however, these conditions were completely resolved with appropriate medications within 2 weeks postoperatively. Univariate logistic regression analyses showed that accumulation of surgical experience ( OR 117.3, P = 0.046) was a significant predictor for stone-free status. Conclusion Carrying out endoscopic combined intrarenal surgery and contralateral retrograde intrarenal surgery in a single session for patients with bilateral stones is feasible and safe. [ABSTRACT FROM AUTHOR]

Background: Severe fever with thrombocytopenia syndrome (SFTS), an emerging viral infectious disease, is mainly transmitted by ticks in the surrounding environment. Clinical progress and risk factors for prognosis in SFTS patients were not yet fully understood. Thus, the objective of this study was to analyze clinical progression and laboratory data related to the prognosis of South Korean SFTS patients in a single institution from 2014 to 2021. Materials and Methods: Fifty-three confirmed SFTS patients from August 2014 to September 2021 at Gyeongsang National University Hospital (GNUH) in Jinju, South Korea were enrolled. Electronic medical records of SFTS patients' demographic features, clinical data, and laboratory data were retrospectively reviewed. Risk factors for fatality were statistically analyzed by classifying enrolled patients into fatal and non-fatal groups. Results: The mean age of patients in the fatal group was significantly higher than that in the non-fatal group (p = 0.036). Hemorrhagic manifestations (p = 0.001) and multiple organ dysfunction (MOD) (p < 0.001) were significantly common in the fatal group. Age, hemorrhagic manifestations, and MOD were also associated with death (p = 0.001, p = 0.008, and p = 0.041, respectively), with adjusted hazard ratios (aHRs) of 1.14, 18.25, and 2.36, respectively. Onset of illness to admission was also significantly associated with death (p = 0.005), with aHR of 0.48. Age, interval from onset of illness to admission, hemorrhagic manifestations, and MOD were found to be variables related to the fatality of SFTS patients. Conclusion: Laboratory test results showed a significant difference between the fatal group and the non-fatal group, but they did not have a statistically significant effect on the prognosis of SFTS patients. [ABSTRACT FROM AUTHOR]

We aimed to determine whether vitamin D levels before prostate biopsy have diagnostic value for clinically significant prostate cancer. The study cohort included patients who underwent prostate biopsy. A total of 224 patients were enrolled in our study and serum vitamin D levels were measured from February 2016 to December 2019 in routine laboratory tests. To determine the relationship between vitamin D levels and aggressiveness of prostate cancer, we used logistic multivariate analysis. Based on the histopathological results of patients who underwent radical prostatectomy, the serum vitamin D level was significantly lower with the large tumor volume group. In the univariate analysis, the prostate cancer diagnosis rate was associated with low vitamin D levels. Low vitamin D level is negatively correlated with clinically significant prostate cancer (biopsy Gleason score of 7 or higher) in the univariate (Odds ratio [OR], 0.955; P < 0.001) and multivariate (OR, 0.944; P = 0.027) analyses. In conclusion, we found that the incidence of clinically significant prostate cancer might related to low vitamin D level in the Asian population. In the future, a larger population and prospective study are needed. [ABSTRACT FROM AUTHOR]

We aimed to assess the relationship between lifestyle-related variables, metabolic syndrome, and lower urinary tract symptoms (LUTS) in men ≥ 40 years. We also assessed the impact of these variables on quality of life. From 2014 to 2020, 5355 men who underwent health check-ups with I-PSS questionnaires at our institute were included in the analysis. The impact of LUTS on sleep disorders and moderate to severe degrees of stress were assessed. Multivariate analysis was performed to determine the variables associated with LUTS and prostate volume. Moderate and severe LUTS were present in 1317 (24.6%) and 211 (3.9%) men, respectively. Moderate and severe LUTS were significantly associated with the presence of sleep disorders and stress. On multivariable analysis, age, amount of life-long smoking, marital status, income, job, and decreased HDL-cholesterol were associated with the presence of moderate to severe LUTS. Although older age and the amount of life-long smoking was associated with both voiding and storage sub-score, socioeconomic status, including marital status and income were only associated with storage sub-score. In men ≥ 40 years, stable socioeconomic status, in addition to older age, and life-long smoking amount are associated with the presence of moderate to severe LUTS, which worsens sleep quality and stress level, by worsen storage sub-score. [ABSTRACT FROM AUTHOR]

To compare the postoperative estimated-glomerular-filtration-rate (eGFR) and parenchymal changes between cold ischemia and zero/selective ischemia for a T1a mass. We analyzed 104 patients who underwent open partial nephrectomy with cold ischemia (53) or zero/selective ischemia (51) for T1a between 2008 and 2018 to determine postoperative renal function changes and associated factors. Postoperative renal function was expressed as (postoperative-eGFR − preoperative-eGFR)/preoperative-eGFR × 100%. Parenchymal enhancement and thicknesses of the ipsilateral kidney as tissue changes were measured on postoperative CT to identify the correlation with the renal function change. Patients with 10% or 25% decrease in eGFR were significantly more in the cold ischemia group (p = 0.032, p = 0.006). On multivariable analysis, preoperative eGFR, ischemic type, and percent change of parenchymal thickness were identified to be significantly associated with postoperative 12 months renal function (B = − 0.367, p = 0.020; B = 6.788, p = 0.042; B = 0.797, p = 0.029). Change in parenchymal thickness was negatively correlated with changes in postoperative renal function (r = − 0.277, p = 0.012). Changes in eGFR were associated with a decrease in parenchymal thickness and the type of ischemic technique. Zero/selective ischemia during partial nephrectomy may have an advantage in preserving postoperative renal function compared to cold ischemia. [ABSTRACT FROM AUTHOR]

The LIM kinases (LIMK1 and LIMK2), known as downstream effectors, and the Rho-associated protein kinase (ROCK), a regulator of actin dynamics, have effects on a diverse set of cellular functions. The LIM kinases are involved in the function of the male urogenital system by smooth muscle contraction via phosphorylation of cofilin and subsequent actin cytoskeleton reorganization. Although LIMK1 and LIMK2 share sequence similarities as serine protein kinases, different tissue distribution patterns and distinct localization during cell cycle progression suggest other biological functions for each kinase. During meiosis and mitosis, the LIMK1/2–cofilin signaling facilitates the orchestrated chromatin remodeling between gametogenesis and the actin cytoskeleton. A splicing variant of the LIMK2 transcript was expressed only in the testis. Moreover, positive signals with LIMK2-specific antibodies were detected mainly in the nucleus of the differentiated stages of germ cells, such as spermatocytes and early round spermatids. LIMK2 plays a vital role in proper spermatogenesis, such as meiotic processes of spermatogenesis after puberty. On the other hand, the literature evidence revealed that a reduction in LIMK1 expression enhanced the inhibitory effects of a ROCK inhibitor on the smooth muscle contraction of the human prostate. LIMK1 may have a role in urethral obstruction and bladder outlet obstruction in men with benign prostatic hyperplasia. Moreover, LIMK1 expression was reduced in urethral stricture. The reduced LIMK1 expression caused the impaired proliferation and migration of urethral fibroblasts. In addition, the activated LIMK2–cofilin pathway contributes to cavernosal fibrosis after cavernosal nerve injury. Recent evidence demonstrated that short-term inhibition of LIMK2 from the immediate post-injury period prevented cavernosal fibrosis and improved erectile function in a rat model of cavernosal nerve injury. Furthermore, chronic inhibition of the LIMK2–cofilin pathway significantly restrained the cavernosal veno-occlusive dysfunction, the primary pathophysiologic mechanism of post-prostatectomy erectile dysfunction through suppressing fibrosis in the corpus cavernosum. In conclusion, the LIM kinases–cofilin pathway appears to play a role in the function of the male urogenital system through actin cytoskeleton reorganization and contributes to the pathogenesis of several urogenital diseases. Therefore, LIM kinases may be a potential treatment target in urogenital disorder. [ABSTRACT FROM AUTHOR]

We determined if combined administration of JNK-inhibitors and HGF (hepatocyte-growth-factor) would restore erectile-function through both antiapoptotic and regenerative effects in a rat model of cavernous-nerve-crush-injury (CNCI), and compared the results with administration of JNK-inhibitor alone or HGF alone. We randomized 70 rats into 5 groups: sham-surgery-group (S), CNCI (I) group, a group treated with once-daily intraperitoneal-administration of 10.0-mg/kg of JNK-inhibitors (J), a twice-weekly intracavernosal-administration of 4.2-μg HGF group (H), and a combined-treatment with 10.0-mg/kg JNK-inhibitors and 4.2-μg HGF group (J+H). We investigated erectile-responses to electrostimulation, histological-staining, caspase-3-activity-assay, and immunoblotting at two-weeks postoperatively. The three treatment groups showed improvements in erectile-responses (ICP/MAP and AUC/MAP ratios) compared to Group-I. The erectile-responses in Group-J+H were greater than those in Group-J or Group-H. The erectile-responses in Group-J+H were generally normalized. Caspase-3-activity and cJun-phosphorylation in Group-J and Group-J+H improved compared to Group-I, whereas caspase-3-activity in Group-H partially improved. Protein-expression of PECAM-1, eNOS-phosphorylation, and smooth-muscle content in Group-J+H were normalized, although those in Group-J or Group-H were partially restored. Combination therapy with JNK-inhibitors and HGF can generally normalize erectile-function through anti-apoptosis and preservation of endothelium or SM in rat CNCI model. The combined treatment appears to be superior to the respective agent alone in terms of therapeutic effects. [ABSTRACT FROM AUTHOR]

Abstract: Biphenolic components in the Magnolia family have shown several pharmacological activities such as antitumor effects. This study investigated the effects of 4-O-methylhonokiol (MH), a constituent of Magnolia officinalis, on human colon cancer cell growth and its action mechanism. 4-O-methylhonokiol (0–30 μM) decreased constitutive activated nuclear factor (NF)-κB DNA binding activity and inhibited growth of human colon (SW620 and HCT116) cancer cells. It also caused G0–G1 phase cell cycle arrest followed by an induction of apoptotic cell death. However, knockdown with small interfering RNA (siRNA) of p21 or transfection with cyclin D1/Cdk4 binding site-mutated p21 abrogated MH-induced cell growth inhibition, inhibition of NF-κB activity as well as expression of cyclin D1 and Cdk4. Conversely, inhibition of NF-κB with specific inhibitor or siRNA augmented MH-induced apoptotic cell death. 4-O-methylhonokiol inhibited tumor growth, NF-κB activity and expression of antiapoptotic proteins; however, it increased the expression of apoptotic proteins as well as p21 in xenograft nude mice bearing SW620 cancer cells. The present study reveals that MH causes p21-mediated human colon cancer cell growth inhibition through suppression of NF-κB and indicates that this compound by itself or in combination with other anticancer agents could be useful for the treatment of cancer. [Copyright &y& Elsevier]

Summary Studies have demonstrated that the anti-tumour effect of natural killer (NK) cells is successful for patients with several cancers. Although interleukin-32 (IL-32) is endogenously expressed in NK cells, cytolytic function of NK cells against cancer cells has not been fully demonstrated. In the present study, we found that the growth of cancer cells was suppressed when colon cancer cells or prostate cancer cells were co-cultured with NK-92 cells, an NK cell line. We also found that the expression of tumour necrosis factor receptor 2 and death receptor 3 (DR3) was increased in PC3 cells, and the expression of FAS and DR3 was increased in SW620 cells by co-culture with NK-92 cells. However, cancer cell growth inhibition and IL-32 expression were abolished when cancer cells were co-cultured with NK cells transfected with small interfering (si) RNA of IL-32. DR3 expression was also diminished by co-culture with IL-32-specific siRNA-transfected NK-92 cells. Expression of APO3L, a ligand of DR3, was elevated in NK cells that were co-cultured with cancer cells. It was also found that expression of apoptosis-related proteins such as cleaved caspase-3 and bax was increased in cancer cells co-cultured with NK-92 cells, but their expression was abolished by co-culture with IL-32 siRNA-transfected NK-92 cells. Moreover, knockdown of DR3 in co-culture of NK-92 cells with cancer cells by siRNA or antibodies of DR3 and APO3L reversed the growth inhibitory effect of NK-92 cells. In conclusion, our study showed that IL-32 enhanced the cytotoxic effect of NK-92 cells on the cancer cells through activation of DR3 and caspase-3. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the effects of dutasteride on the expression of angiogenesis markers in rat and human prostates. Material and methods. Eight-week-old male Sprague–Dawley rats were divided into three groups of six each according to dutasteride dose, including the control group (regular diet), 2.5 mg group (2.5 mg/kg dutasteride) and 5.0 mg group (5.0 mg/kg dutasteride). A total of 41 patients awaiting transurethral resection of the prostate (TURP) were divided into two groups: 20 patients received no medication and 21 received 0.5 mg dutasteride daily for 2–4 weeks until TURP. Results. At 2 weeks, dutasteride effected a significant decrease in body weight and prostate weight compared with the control rat group. Analysis by reverse transcription–polymerase chain reaction and Western blot revealed that hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression was lower in the dutasteride-treated groups than in the control group, except for HIF-1α protein. HIF-1α and VEGF expression was similar in the 2.5 mg and 5.0 mg groups. Human prostate tissues demonstrated homogeneous staining of HIF-1α and VEGF with regard to extent, intensity and intracellular location in both groups. There was no significant difference in microvessel density between the two groups. Conclusions. The expression of HIF-1α and VEGF in rat prostates is suppressed by dutasteride. However, less than 4 weeks of dutasteride administration does not suppress the expression of HIF-1α, VEGF and microvessel density in human prostate tissue. Further clinical investigation with dutasteride including a larger, placebo-controlled study is warranted to establish the mechanism and duration of dutasteride. [ABSTRACT FROM AUTHOR]

We aimed to identify and compare microRNAs (miRNAs) from individual aqueous humor samples between normal-tension glaucoma (NTG) patients and normal controls. Aqueous humor (80 to 120 µl) was collected before cataract surgery. Six stable NTG patients and seven age-matched controls were included in the final analysis. RNA sequencing was conducted for RNA samples extracted from the 13 aqueous humor samples, and bioinformatics analysis was employed for the miRNA targets and related pathways. Two hundred and twenty-eight discrete miRNAs were detected in the aqueous humor and consistently expressed in all samples. Eight significantly upregulated miRNAs were found in the NTG patients compared to the controls (fold-change > 2, p < 0.05). They were hsa-let-7a-5p, hsa-let-7c-5p, hsa-let-7f-5p, hsa-miR-192-5p, hsa-miR-10a-5p, hsa-miR-10b-5p, hsa-miR-375, and hsa-miR-143-3p. These miRNAs were predicted to be associated with the biological processes of apoptosis, autophagy, neurogenesis, and aging in the gene ontology categories. The related Kyoto encyclopedia of genes and genomes pathways were extracellular matrix-receptor interaction, mucin-type O-glycan biosynthesis, biotin metabolism, and signaling pathways regulating the pluripotency of stem cells. The differentially expressed miRNA in the NTG samples compared to the controls suggest the possible roles of miRNA in the pathogenesis of NTG. The underlying miRNA-associated pathways further imply novel targets for the pathogenesis of NTG. [ABSTRACT FROM AUTHOR]

Previous epidemiological studies have demonstrated that the lower serum concentration of vitamin D was associated with elevated risk of open-angle glaucoma (OAG). However, few studies have examined the association between aqueous humor vitamin D concentrations and OAG. Hence, we investigated the relationship between 25-hydroxyvitamin D (25(OH)D) concentrations in aqueous humor and OAG. We measured 25(OH)D concentrations in aqueous humor and serum of 126 patients who underwent cataract surgery. 36 were patients with OAG and 90 were control patients. The 25(OH)D concentrations were measured using Elecsys Vitamin D Total Kits with the Cobas e602 module (Roche Diagnostics, Mannheim, Germany), an electrochemiluminescence assay. Multiple linear regression analysis was performed to investigate factors associated with serum and aqueous humor 25(OH)D concentrations. Patients with OAG had significantly lower 25(OH)D concentrations in aqueous humor than control patients. Serum 25(OH)D concentrations were higher in patients with OAG than in the control, but this was not statistically significant. 25(OH)D concentrations in aqueous humor of patients with OAG were significantly associated with axial length but not with glaucoma severity, which was determined by the retinal nerve fiber layer thickness or mean deviation. Vitamin D concentrations in aqueous humor of patients with OAG were significantly lower than those in patients without OAG. [ABSTRACT FROM AUTHOR]

Previous studies have reported conflicting results on the predictive role of the platelet-to-lymphocyte ratio (PLR) in detecting clinically significant prostate cancer (CSPCa) at the time of prostate biopsies. We explored the predictive value of pre-biopsy PLRs for CSPCa using our large-cohort database. Consecutive men with serum prostate-specific antigen (PSA) levels of ≥ 3.0 ng/mL or abnormal digital rectal examination (DRE) findings and who underwent prostate biopsies were included in the study. There was no significant difference in the pre-biopsy PLR between men with benign disease, clinically insignificant prostate cancer (CISPCa), and CSPCa. Only the subset of CSPCa patients with serum PSA levels of < 10 ng/mL showed lower PLRs than those with benign disease or CISPCa. In the entire patient cohort, multivariate analyses revealed that older age, diabetes mellitus, DRE abnormalities, higher serum PSA levels, and smaller prostate volume were predictors of CSPCa. However, the pre-biopsy PLR was not a significant predictor of CSPCa at the prostate biopsy in the entire patient cohort or the subset of patients with serum PSA levels of < 10 ng/mL. In summary, the pre-biopsy PLR is not an independent predictor of CSPCa at the prostate biopsy, regardless of the serum PSA level. [ABSTRACT FROM AUTHOR]

Aim of the study is to report the clinical characteristics and prognostic factors in hypertensive anterior uveitis (AU) diagnosed with multiplex polymerase chain reaction (PCR). Eighty-eight eyes of 88 patients with hypertensive AU were enrolled from 2015 to 2019 in a tertiary center in South Korea. All patients underwent multiplex PCR that was performed using aqueous humor samples collected at first visit to detect the DNA of six herpesviruses. Twenty-eight (31.8%) eyes were PCR positive. Herpes simplex virus was found in 6 (6.8%) eyes, varicella-zoster virus in 7 (8.0%) eyes, cytomegalovirus in 14 (15.9%) eyes, and Epstein–Barr virus in 1 (1.1%) eye. On multivariate regression analysis, PCR positivity was significantly associated with coin-shaped keratic precipitates (odds ratio (OR) = 6.01, P = 0.044). Recurrence and final visual acuity were significantly associated with a presumed diagnosis of viral endotheliitis (OR = 21.69, P = 0.04 and OR = 6.3, P = 0.004, respectively). This study showed the importance of PCR positivity, suggesting that identification of the virus through active PCR testing could affect the course, treatment, and prognosis of hypertensive AU. [ABSTRACT FROM AUTHOR]

Background: Vitamin D status is presently assessed by measuring total serum concentration of 25-hydroxyvitamin D [25(OH)D]. However, 25(OH)D concentration alone might not accurately reflect vitamin D status owing to its weak relationship with various clinical indices and inconsistency across races. Recently, 24,25-dihydroxyvitamin D [24,25(OH)2D] and vitamin D metabolite ratio [VMR; ratio of 24,25(OH)2D to 25(OH)D] have emerged as vitamin D biomarkers. The present study aimed to determine the values of 24,25(OH)2D and VMR in healthy Koreans and compare them with other vitamin D biomarkers, including 25(OH)D and bioavailable 25(OH)D. Methods: Serum samples and medical information were collected from 200 individuals (100 females and 100 males) who underwent general health checks without self-reported symptoms. We measured 24,25(OH)2D concentration using liquid chromatography–tandem mass spectrometry, and concentrations of 25(OH)D and vitamin D binding protein using immunoassays. VMR and bioavailable 25(OH)D concentration were calculated using the above data. Serum parathyroid hormone level, and bone mineral density (BMD) data were collected as clinical outcomes, and the effects of the vitamin D markers on them were tested using multiple linear regression models. Results: The mean values of 25(OH)D, 24,25(OH)2D, VMR, and bioavailable 25(OH)D were 24.3 ± 8.5 ng/mL, 1.9 ± 1.1 ng/mL, 7.6 ± 2.5, and 3.2 ± 1.2 ng/mL, respectively. The concentration of 25(OH)D closely correlated with 24,25(OH)2D (R = 0.868, P < 0.001) and bioavailable 25(OH)D (R = 0.862, P < 0.001). No significant effects of 24,25(OH)2D, VMR, and bioavailable 25(OH)D were observed on the prediction of PTH and BMD in the multiple linear regression models. Conclusion: Our study presents the distribution of 24,25(OH)2D concentration and VMR in Korean population for the first time. Overall, our data reaffirm that 25(OH)D is the primary marker for determining vitamin D status in the general population. [ABSTRACT FROM AUTHOR]