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We aimed to investigate the impact of various bladder lesions on the clinical symptoms and recurrence of interstitial cystitis (IC).Patients with IC who underwent transurethral resection and cauterization for Hunner lesions (HLs) were enrolled. Features of HLs-noninflamed, inflamed, and gradually inflamed-and associated cystoscopic findings, including waterfall bleeding (none, focal or extensive), submucosal hemorrhage, and mucosal streak, were analyzed to investigate their association with preoperative symptoms and recurrence.We included 272 procedures from 141 patients (male:female ratio 37:104) with a mean±SD age of 61.4±10.5 years. Recurrence was observed in 160 procedures after a mean of 15.6 months (range 0.7-91.7); repeat transurethral resection and cauterization was performed in 131 cases. The number of HLs observed at each procedure was variable, and sufficient bladder filling revealed hidden lesions in 10.7% of cases. Waterfall bleeding was frequently accompanied with inflamed/gradually inflamed HLs. Inflammatory HLs were associated with smaller functional bladder capacity and preoperative urgency (p=0.007). Extensive waterfall bleeding was associated with smaller functional bladder capacity (p=0.006). On multivariate analysis, initially inflamed HLs (HR: 1.675, 95% CI: 1.022-2.746, p=0.041) and gradual inflammatory changes in HLs (HR: 1.893, 95% CI: 1.050-3.410, p=0.034) were found to be risk factors for recurrence.Sufficient bladder filling revealed hidden HLs. The features of HLs were not associated with subjective symptoms; inflamed changes were a predictive factor for IC recurrence, and associated with frequent urgency episodes and smaller bladder capacity.

Background The therapeutic effects of human embryonic stem cell-derived multipotent mesenchymal stem cells (M-MSCs) were evaluated for detrusor underactivity (DUA) in a rat model with atherosclerosis-induced chronic bladder ischemia (CBI) and associated mechanisms. Methods Sixteen-week-old male Sprague–Dawley rats were divided into five groups (n = 10). The DUA groups underwent 30 bilateral repetitions of endothelial injury to the iliac arteries to induce CBI, while the sham control group underwent a sham operation. All rats used in this study received a 1.25% cholesterol diet for 8 weeks. M-MSCs at a density of 2.5, 5.0, or 10.0 × 105 cells (250 K, 500 K, or 1000 K; K = a thousand) were injected directly into the bladder 7 weeks post-injury, while the sham and DUA group were treated only with vehicle (phosphate buffer solution). One week after M-MSC injection, awake cystometry was performed on the rats. Then, the bladders were harvested, studied in an organ bath, and prepared for histological and gene expression analyses. Results CBI by iliac artery injury reproduced voiding defects characteristic of DUA with decreased micturition pressure, increased micturition interval, and a larger residual volume. The pathological DUA properties were improved by M-MSC treatment in a dose-dependent manner, with the 1000 K group producing the best efficacy. Histological analysis revealed that M-MSC therapy reduced CBI-induced injuries including bladder fibrosis, muscular loss, and apoptosis. Transplanted M-MSCs mainly engrafted as vimentin and NG2 positive pericytes rather than myocytes, leading to increased angiogenesis in the CBI bladder. Transcriptomes of the CBI-injured bladders were characterized by the complement system, inflammatory, and ion transport-related pathways, which were restored by M-MSC therapy. Conclusions Single injection of M-MSCs directly into the bladder of a CBI-induced DUA rat model improved voiding profiles and repaired the bladder muscle atrophy in a dose-dependent manner. Graphical abstract

Purpose To determine the limitations of current screening methods for lipid disorders and to suggest a new method that is effective for use in Korean adolescents. Methods Data from the 6th Korea National Health and Nutrition Examination Survey (2013-2015) were analyzed. The diagnostic validity (sensitivity and specificity) of various cardiovascular risk factors currently used for lipid disorder screening was investigated, as was the diagnostic validity of non-HDL-cholesterol ≥145 mg/dL as a screening tool. Results The prevalence of dyslipidemia and familial hypercholesterolemia (FH) among Korean adolescents was 20.4%±1.0% and 0.8%±0.3%, respectively. The current standard screening methods identified only 5.9%±1.4% and 30.3%±17.2% of the total number of dyslipidemia and FH cases, respectively. The diagnostic sensitivity and specificity of lipid profile analysis for dyslipidemia among obese adolescents were 19.5%±2.3% and 93.6%±0.8% and for FH were 30.3%±17.2% and 91.1%±0.8%, respectively. When adolescents with obesity, hypertension, or a family history of dyslipidemia or cardiocerebrovascular disease for over 3 generations were included in the screening, diagnostic sensitivity increased to 68.4%±2.8% for dyslipidemia and 83.5%±2.7% for FH. Universal screening of all adolescents based on non-HDL-cholesterol levels had sensitivities of 30.2%±2.7% and 100%, and specificities of 99.2%±0.3% and 94%±0.6% for dyslipidemia and FH, respectively. Conclusion New screening methods should be considered for early diagnosis and treatment of lipid disorders in Korean adolescents.

Familial hypophosphatemic rickets (FHR) is a disorder characterized by phosphate wasting and hypophosphatemia due to defects in renal phosphate transport regulation. There are 4 known inherited forms of FHR that differ in their molecular causes. Very few studies have been conducted that focused on the molecular analysis of FHR in Koreans. Eighteen mutations of the PHEX gene have been identified to this date in Korea. Herein, we report the clinical case of a 24-month-old boy presenting with bowed legs and short stature. The biochemical profile showed hypophosphatemia with decreased tubular reabsorption of phosphate. Several family members were identified with short stature and genu varum. Therefore, he was diagnosed with FHR. To identify the molecular causes of FHR, we performed targeted gene panel sequencing and found a novel hemizygous missense variant, c.1949T>C (p.Leu650Pro), in the PHEX gene. This variant was also detected in the boy’s mother who exhibited genu varum and short stature.

We tried to establish a reliable detrusor underactivity (DUA) rat model and to investigate pathophysiology of chronic bladder ischemia (CBI) on voiding behavior and bladder function. Adult male rats were divided into five groups. The arterial injury (AI) groups (AI-10, AI-20, AI-30) underwent vascular endothelial damage (VED) of bilateral iliac arteries (with 10, 20, and 30 bilateral repetitions of injury, respectively) and received a 1.25% cholesterol diet. The sham group underwent sham operation and received the same diet. Controls received a regular diet. After 8 weeks, all rats underwent unanesthetized cystometrogram. Bladder tissues were processed for organ bath investigation, immunohistochemistry staining, and genome-wide gene expression analysis. Awake cystometry analysis showed that frequency of voiding contractions and micturition pressure were lower in the AI-30 group than in sham group (p

ObjectiveTo evaluate the differences in urodynamic findings between multiple system atrophy (MSA) and Parkinson disease (PD) and to identify the differential diagnostic ability of urodynamic study.MethodsWe reviewed patients with MSA or PD who underwent urodynamic studies between January 2011 and August 2018. Patients with probable MSA and PD determined by movement disorder specialists at our center were included. Patients with alleged MSA or PD from outside hospitals, atypical or secondary parkinsonism, and any history of pelvic operation or radiation therapy were excluded.ResultsA total of 219 patients, 107 with MSA (male:female 50:57) and 112 with PD (male:female 57:55), were included. Patients with MSA had shorter disease duration and were referred for urologic evaluation earlier (p < 0.001). Detrusor overactivity and associated urine leakage were prominent in PD (p < 0.001). Patients with MSA showed lower maximal flow rate (4.0 ± 5.8 vs 9.1 ± 8.3 mL/s, p < 0.001) and larger postvoid residual (290.8 ± 196.7 vs 134.0 ± 188.1 mL, p < 0.001) with decreased compliance (44.9% vs 10.7%, p < 0.001) and impaired contractility (24.9 ± 33.8 vs 65.7 ± 51.1, p < 0.001). Postvoid residual from a pressure-flow study had the highest sensitivity and specificity (74.8% and 75.9%), followed by detrusor pressure at maximal uroflow (72.6% and 70.5%), bladder contractility index, and postvoid residual from uroflowmetry (71.0% and 70.5%, respectively).ConclusionsPatients with MSA showed lower maximal flow rate, larger postvoid residual with decreased compliance, and impaired contractility, whereas patients with PD had higher incidence of detrusor overactivity and associated leakage. For differential diagnosis, postvoid residual from a pressure-flow study provided the best sensitivity and specificity.Classification of evidenceThis study provides Class III evidence that urodynamic measures can distinguish patients with MSA from those with PD.

Mesenchymal stem cell (MSC) therapy is a promising treatment for various intractable disorders including interstitial cystitis/bladder pain syndrome (IC/BPS). However, an analysis of fundamental characteristics driving in vivo behaviors of transplanted cells has not been performed, causing debates about rational use and efficacy of MSC therapy. Here, we implemented two-photon intravital imaging and single cell transcriptome analysis to evaluate the in vivo behaviors of engrafted multipotent MSCs (M-MSCs) derived from human embryonic stem cells (hESCs) in an acute IC/BPS animal model. Two-photon imaging analysis was performed to visualize the dynamic association between engrafted M-MSCs and bladder vasculature within live animals until 28 days after transplantation, demonstrating the progressive integration of transplanted M-MSCs into a perivascular-like structure. Single cell transcriptome analysis was performed in highly purified engrafted cells after a dual MACS−FACS sorting procedure and revealed expression changes in various pathways relating to pericyte cell adhesion and cellular stress. Particularly, FOS and cyclin dependent kinase-1 (CDK1) played a key role in modulating the migration, engraftment, and anti-inflammatory functions of M-MSCs, which determined their in vivo therapeutic potency. Collectively, this approach provides an overview of engrafted M-MSC behavior in vivo, which will advance our understanding of MSC therapeutic applications, efficacy, and safety.

Mesenchymal stem/stromal cell (MSC) therapy is a promising approach for treatment of as yet incurable detrusor underactivity (DUA), which is characterized by decreased detrusor contraction strength and/or duration, leading to prolonged bladder emptying. In the present study, we demonstrated the therapeutic potential of human embryonic stem cell (ESC)-derived multipotent MSCs (M-MSCs) in a diabetic rat model of DUA. Diabetes mellitus (DM) was induced by intraperitoneal injection of streptozotocin (STZ) (50 mg/kg) into 8-week-old female Sprague-Dawley rats. Three weeks later, various doses of M-MSCs (0.25, 0.5, and 1 × 106 cells) or an equivalent volume of PBS were injected into the outer layer of the bladder. Awake cystometry, organ bath, histological, and gene expression analyses were evaluated 1 week (short-term) or 2 and 4 weeks (long-term) after M-MSC transplantation. STZ-induced diabetic rats developed DUA, including phenotypes with significantly longer micturition intervals, increased residual urine amounts and bladder capacity, decreased micturition pressure on awake cystometry, and contractile responses to various stimuli in organ bath studies. Muscle degeneration, mast cell infiltration, fibrosis, and apoptosis were present in the bladders of DM animals. A single local transplantation of M-MSCs ameliorated DUA bladder pathology, including functional changes and histological evaluation, and caused few adverse outcomes. Immunostaining and gene expression analysis revealed that the transplanted M-MSCs supported myogenic restoration primarily by engrafting into bladder tissue via pericytes, and subsequently exerting paracrine effects to prevent apoptotic cell death in bladder tissue. The therapeutic efficacy of M-MSCs was superior to that of human umbilical cord-derived MSCs at the early time point (1 week). However, the difference in efficacy between M-MSCs and human umbilical cord-derived MSCs was statistically insignificant at the later time points (2 and 4 weeks). Collectively, the present study provides the first evidence for improved therapeutic efficacy of a human ESC derivative in a preclinical model of DM-associated DUA.

Purpose Despite advances in flexible ureteroscopy, the high cost and long repair time of ureteroscopes limit their use in the urology. We compared the performance of a novel flexible ureteroscope (fURS) 'HF-EH' with that of the two contemporary fURSs 'URF-P6' and 'COBRA'. Materials and methods We compared in vitro measurements of deflection angle, irrigation flow rate, and image quality between HF-EH and URF-P6 while also inspecting renal collecting systems in five female pigs. For clinical testing, we performed retrograde intrarenal surgeries using HF-EH in four patients. Experienced urologists compared performance parameters (irrigation, convenience, and maneuverability) between the HF-EH and COBRA. Results The flow rate of HF-EH (21.0 mL/min) was worse, and its resolution (1.59 line pairs/mm) was inferior to that of URF-P6 (28.7 mL/min and 3.17 line pairs/mm, respectively). However, HF-EH was superior to URF-P6 in terms of loss of deflection angle with the insertion of accessories (1.8% vs. 12.7%). In vivo and clinical testing revealed that the performance parameters of HF-EH were slightly inferior to those of conventional domestic fURSs. We successfully performed retrograde intrarenal surgeries using HF-EH in four patients and achieved stone-free statuses in two. None of the patients exhibited any procedure-related complications. Conclusions Although we observed that two of the three performance parameters of the novel ureteroscope 'HF-EH' were inferior to those of the conventional ureteroscope, we successfully used HF-EH to perform retrograde intrarenal surgeries in patients. Further studies on performance and durability are warranted for making HF-EH commercially available.

Purpose To evaluate the therapeutic effect of human embryonic stem cell (hESC)-derived multipotent mesenchymal stem cells (M-MSCs) on ketamine-induced cystitis (KC) in rats. Methods To induce KC, 10-week-old female rats were injected with 25-mg/kg ketamine hydrochloride twice weekly for 12 weeks. In the sham group, phosphate buffered saline (PBS) was injected instead of ketamine. One week after the final injection of ketamine, the indicated doses (0.25, 0.5, and 1×106 cells) of M-MSCs (KC+M-MSC group) or PBS vehicle (KC group) were directly injected into the bladder wall. One week after M-MSC injection, the therapeutic outcomes were evaluated via cystometry, histological analyses, and measurement of gene expression. Next, we compared the efficacy of M-MSCs at a low dose (1×105 cells) to that of an identical dose of adult bone marrow (BM)-derived MSCs. Results Rats in the KC group exhibited increased voiding frequency and reduced bladder capacity compared to rats of the sham group. However, these parameters recovered after transplantation of M-MSCs at all doses tested. KC bladders exhibited markedly increased mast cell infiltration, apoptosis, and tissue fibrosis. Administration of M-MSCs significantly reversed these characteristic histological alterations. Gene expression analyses indicated that several genes associated with tissue fibrosis were markedly upregulated in KC bladders. However the expression of these genes was significantly suppressed by the administration of M-MSCs. Importantly, M-MSCs ameliorated bladder deterioration in KC rats after injection of a low dose (1×105) of cells, at which point BM-derived MSCs did not substantially improve bladder function. Conclusions This study demonstrates for the first time the therapeutic efficacy of hESC-derived M-MSCs on KC in rats. M-MSCs restored bladder function more effectively than did BM-derived MSCs, protecting against abnormal changes including mast cell infiltration, apoptosis and fibrotic damage.

Rationale: Mesenchymal stem cell (MSC) therapy may be a novel approach to improve interstitial cystitis/bladder pain syndrome (IC/BPS), an intractable disease characterized by severe pelvic pain and urinary frequency. Unfortunately, the properties of transplanted stem cells have not been directly analyzed in vivo, which hampers elucidation of the therapeutic mechanisms of these cells and optimization of transplantation protocols. Here, we monitored the behaviors of multipotent stem cells (M-MSCs) derived from human embryonic stem cells (hESCs) in real time using a novel combination of in vivo confocal endoscopic and microscopic imaging and demonstrated their improved therapeutic potency in a chronic IC/BPS animal model. Methods: Ten-week-old female Sprague-Dawley rats were instilled with 10 mg of protamine sulfate followed by 750 μg of lipopolysaccharide weekly for 5 weeks. The sham group was instilled with phosphate-buffered saline (PBS). Thereafter, the indicated dose (0.1, 0.25, 0.5, and 1×106 cells) of M-MSCs or PBS was injected once into the outer layer of the bladder. The distribution, perivascular integration, and therapeutic effects of M-MSCs were monitored by in vivo endoscopic and confocal microscopic imaging, awake cystometry, and histological and gene expression analyses. Results: A novel combination of longitudinal intravital confocal fluorescence imaging and microcystoscopy in living animals, together with immunofluorescence analysis of bladder tissues, demonstrated that transplanted M-MSCs engrafted following differentiation into multiple cell types and gradually integrated into a perivascular-like structure until 30 days after transplantation. The beneficial effects of transplanted M-MSCs on bladder voiding function and the pathological characteristics of the bladder were efficient and long-lasting due to the stable engraftment of these cells. Conclusion: This longitudinal bioimaging study of transplanted hESC-derived M-MSCs in living animals reveals their long-term functional integration, which underlies the improved therapeutic effects of these cells on IC/BPS.

Purpose: To investigate the incidence and risk factors associated with persistent urinary frequency, and to evaluate the efficacy of antimuscarinic treatment.Materials and Methods: Interstitial cystitis/bladder pain syndrome (IC/BPS) patients complaining of persistent urinary frequency despite improved pain were evaluated. Before initial conventional treatment, each patient completed a voiding diary and symptom questionnaires. After conventional treatment, patients were divided according to the presence of pain and frequency. Improved pain was defined as lesser than 3 points in visual analogue scale, and persistent urinary frequency as >10 times/d. Risk factors for persistent frequency were identified through multivariate analysis. The efficacy of antimuscarinic treatment was assessed by the mean change of frequency.Results: Of 171 IC/BPS patients treated with conventional therapy, 132 had improved pain after 3 months, but 72 had persistent fre-quency (72 of 132, 54.5%). Patients with persistent frequency had lower voided volume (p=0.008), lower maximal flow rate (p

Objective A pilot randomized trial assessed the feasibility and effectiveness of an intervention combining Smartcare (activity tracker with a smartphone application) and financial incentives. Methods A three-arm, open-label randomized controlled trial design involving traditional education, Smartcare, and Smartcare with financial incentives was involved in this study. The latter group received financial incentives depending on the achievement of daily physical activity goals (process incentive) and weight loss targets (outcome incentive). Male university students (N = 105) with body mass index of ≥27 were enrolled. Results The average weight loss in the traditional education, Smartcare, and Smartcare with financial incentives groups was −0.4, −1.1, and −3.1 kg, respectively, with significantly greater weight loss in the third group (both Ps

Therapeutic options for non-Hunner type interstitial cystitis (IC), which is histologically characterized by fibrosis and mast cell infiltration, are limited. We developed a rat model that replicates chronic inflammation and fibrosis and evaluated the therapeutic effect of N-acetylcysteine (NAC), a well-known anti-fibrotic agent, on the model. Intravesical instillation of lipopolysaccharide (LPS, 750 μg) after protamine sulfate (10 mg) was conducted twice per week for five consecutive weeks. One week after final instillation, 200 mg/kg NAC (n = 10, IC + NAC group) or phosphate-buffered saline (n = 10, IC group) was daily injected intraperitoneally once daily for 5 days. LPS instillation induced bladder fibrosis, mast cell infiltration, and apoptotic tissue damage. Functionally, LPS insult led to irregular micturition, decreased inter-contraction intervals, and decreased micturition volume. NAC significantly improved most of the voiding parameters and reversed histological damages including fibrosis. NAC inhibited the induction and nuclear localization of phospho-Smad2 protein in bladder tissues and the upregulation of genes related to fibrosis, such as Tgfb2, Tgfb3, Smad2, Smad3, Cxcl10, and Card10. This is the first study to demonstrate the beneficial effects on NAC in restoring voiding function, relieving tissue fibrosis and related bladder injuries, in the LPS-induced cystitis rat model.

Choi, Soo Jung; Shin, Dong Wook; Park, Hyun Jung et al..February, 2016.Potential barriers limiting Myanmar migrant workers from using healthcare services in South Korea,Article,[Seoul]Korean Academy of Family Medicine,6

OBJECTIVES To evaluate the effectiveness and persistence of mirabegron as a first-line treatment in patients with overactive bladder (OAB) in real-life practice. METHODS We retrospectively analyzed patients with OAB who received mirabegron (50 mg) as a first-line treatment. According to treatment course, patients were divided into three groups, (a) mirabegron only (monotherapy group), (b) mirabegron and anticholinergics (add-on group), and (c) mirabegron replaced with another treatment (switch group). The patients' symptoms were documented with a voiding diary including an urgency scale and a patient perception of treatment benefit questionnaire (PPTB). Follow-up was at 4 weeks after initial treatment and then 2 months later, according to our routine protocol. RESULTS A total of 196 patients were included: 128 patients (65.3%) received monotherapy and 60 patients (30.6%) received add-on therapy. Eight patients discontinued mirabegron and switched to another treatment modality. The add-on group had more episodes of baseline urinary frequency, nocturia and urgency than the monotherapy group (P = 0.011, 0.001, and 0.006, respectively). In the monotherapy group, mean daily frequency, nocturia, urgency episodes, and urgency urinary incontinence were improved (P

This study assessed the functional role of WNT genes and the association between WNT signalling cascades and fibrosis in interstitial cystitis/bladder pain syndrome (IC/BPS) patients. Twenty-five patients (3 males, 22 females; mean age 59.7 ± 10.9 years), included 7 non-Hunner-type IC (NHIC), 18 Hunner-type IC (HIC), and 5 non-IC (control) groups. The expression of sonic hedgehog, WNT gene family, and genes previously reported as biomarkers for IC/BPS were examined using RT-PCR in biopsy specimens from the mucosa and submucosa layer of the bladder. WNT2B, WNT5A, WNT10A, and WNT11 functions in the urothelium were evaluated by silencing in an HBlEpC cell line. Pelvic Pain and Urgency/Frequency Patient Symptom Scale scores, O’Leary-Sant Symptom and Problem Index scores, and Visual Analogue Scores did not differ between the NHIC and HIC groups. However, HIC patients had significantly shorter symptom duration (30.9 vs 70.8 months, p = 0.046), higher daily urinary frequency (16.1 versus 8.5 times, p = 0.006), and smaller bladder capacity (208.6 versus 361.4 ml, p = 0.006) than NHIC patients. Overall WNT gene expression was lower in NHIC than HIC patients. Bladder epithelial tissues from HIC patients were characterised by the downregulation of WNT11. Silencing of WNT11, WNT2B, WNT5A, and WNT10A in HBlEpCs resulted in fibrotic changes, indicated by fibrotic morphology, increased fibrosis-related gene expression, and nuclear localisation of phosphorylated SMAD2, and increased vimentin and fibronectin levels. Downregulation of WNT11 results in fibrotic changes of bladder epithelial cells and is associated with the pathogenesis and differential diagnosis of NHIC. Decreased expression of WNT11 is a potential biomarker for predicting NHIC.

Background To report the long-term outcomes of endoscopic surgery (ES) in pediatric patients with vesicoureteral reflux in terms of success rate, urinary tract infection, and renal function. Methods We retrospectively reviewed the records of 73 pediatric patients (110 ureters) who underwent ES for vesicoureteral reflux. Ultrasonography was performed 1, 3, and 12 months postoperatively. Voiding cystourethrography was performed 3 months postoperatively and repeated after 1 year if vesicoureteral reflux persisted. Success was defined as the absence of reflux at the first voiding cystourethrography. Renal scans were performed at least 12 months postoperatively. Renal function deterioration was defined as a new scar or a greater than 5% decrease in function. Results The median follow-up duration was 24 (12-118) months. The overall success was 65.6%, while it was 78.9%, 87.0%, 62.5%, 37.5%, 66.7% for grades I, II, III, IV, and V, respectively. In multivariate analyses, significant predictive factors for success were vesicoureteral reflux grade (odds ratio [OR], 0.28; P < 0.001) and mound detection at the first postoperative ultrasonography (OR, 13.53; P < 0.001). Renal function deterioration was found in 8 (15.3%) ureters and was less common in those with successful surgeries than in those with failures (9.5% vs. 40.0%; P = 0.035). No significant predictive factor for renal function deterioration or urinary tract infection was found. Conclusion Successful short-term outcomes of ES are expected in low-grade vesicoureteral reflux, especially when a mound is detected by postoperative ultrasonography. However, unpredictable long-term renal deterioration warrants continued follow-up.

Smoking is a major risk factor of cardiovascular disease (CVD) such as stroke and ischemic heart disease. Prior studies have observed people continued smoking even after being diagnosed with CVD. However, population-level data regarding smoking behavior changes among people who are diagnosed with CVD are still lacking. From the National Health Insurance sample cohort database, we identified 1,700 patients diagnosed as having CVD between 2003 and 2012, and underwent the national health screening examination in the year before and after the CVD event. We found that 486 (28.6%) were smokers before the CVD event. Among them, 240 (49.4%) continued to smoke despite the diagnosis. We observed that a higher smoking amount and longer smoking duration before the diagnosis were associated with persistent smoking. Our finding that approximately 50% of smokers continue smoking even after CVD events supports the need for an assessment of patients' smoking statuses during follow-up after a CVD event and for health-care providers to offer the appropriate smoking cessation interventions to those who continue smoking.

Purpose: To evaluate de novo and resolved urgency and urgency urinary incontinence (UUI) after midurethral sling operations in patients with stress urinary incontinence (SUI) and mixed urinary incontinence (MUI). Materials and Methods: Patients who underwent midurethral sling operations because of SUI and MUI between January 2012 and December 2016 were reviewed. Patients were divided into three groups (pure SUI, SUI with urgency, and MUI). Patients with MUI were subcategorized as SUI predominant, equivalent, and UUI predominant. Postoperative de novo, persistent or disappearance of urgency or UUI were compared. Results: A total of 334 patients were included: 76 with pure SUI, 78 with SUI with urgency, and 180 with MUI. In the MUI group, 138 patients were SUI predominant, 12 patients were equivalent, and 30 patients were UUI predominant. De novo urgency developed in 5 patients (6.6%) in the pure SUI group. In the SUI with urgency group, 51 patients (65.4%) became urgency-free, and 3 (3.8%) developed de novo UUI. UUI resolved in 135 patients (75.0%): 110 (79.7%) in the SUI-predominant group, 9 (75.0%) in the equivalent group, and 16 (53.3%) in the UUI-predominant group. The patients' preoperative perception of predominant UUI was the predictive factor for persistent UUI in the multivariate analysis (hazard ratio, 5.722; p=0.001). Conclusions: De novo urgency and UUI developed in a relatively small number of patients after a midurethral sling operation. The resolution rate of UUI was significantly low in patients who had previous pelvic surgery or who preoperatively perceived UUI as a more bothersome symptom.

The most common complication of implant ball attachments is loss of retention via structural wear. Hence, parallel placement of implants was identified as a prerequisite for long-term success. In this case, although severe angulation was formed between implants due to severe alveolar bone resorption, parallel ball attachments on the implants could be fabricated using computer-aided design/computer-assisted manufacture. This procedure can be a solution when implants are placed with angulation and offers additional advantages such as long-term stability.

Benign childhood epilepsy with centrotemporal spikes (BCECTS), also known as Rolandic epilepsy, is the most common benign childhood epilepsy. Centrotemporal spikes are characteristic findings on electroencephalography (EEG). Though the condition is considered benign, many studies have reported some degree of neuropsychological impairment in individuals with BCECTS. There is also growing evidence from neuroimaging studies that BCECTS may affect a larger portion of the brain than originally thought. We performed distributed source localization analysis of interictal spikes in BCECTS. Current-source density (CSD) of the maximal negative peak of the interictal spikes averaged from each of 20 EEG epochs in 11 patients with BCECTS was measured using standardized low-resolution brain electromagnetic tomography (sLORETA). Rolandic area was included in the distribution of the CSD in all of the patients. The significant CSD and its maximal point were distributed in multiple cortical regions over the Rolandic area. It is suggested that the widespread cortical distribution of interictal spikes seen in this study may be associated with atypical presentation and a variety of comorbidities of BCECTS. Our results imply that BCECTS represents a deviation from normal development during a critical period of brain maturation and that children with BECTS might be more likely to need special medical attention.

INTRODUCTION AND OBJECTIVES: Patients with overactive bladder (OAB) might have phasic detrusor overactivity (DO), terminal DO, and DO with inadequate contractility (DHIC). This study investigated the functional receptor expressions in the urothelium in OAB patients with different urodynamic characteristics. METHODS: The bladder mucosal biopsies of OAB patients and 12 controls were investigated. Western blot and immunohistochemistry were performed to determine the protein expression levels of M2, M3, beta-3 AR, and P2X3 in the tissue. The receptor density and ratio of M2 to M3, and M3 to Beta-3 AR was compared between groups and further correlated with urodynamic results. RESULTS: A total of 57 OAB patients and 12 controls were enrolled. OAB patients had lower M2 expression (0.25 0.41 v 0.83 0.49, p1⁄40.001) and M2/M3 ratio (0.73 1.68 v 1.99 1.79, p1⁄40.01) than that of the controls. Compared with terminal DO, patients with phasic DO had higher expression of beta-3 AR (Table 1). Patients with BOO had higher beta-3 AR than non-BOO group, and lower M3 expressions than the controls (Table 2). The expression of P2X3 receptors was significantly correlated with beta-3 AR (p1⁄40.003) as well as with M3 (p1⁄40.032) (Fig. 1). CONCLUSIONS: Beta-3 AR expression was significantly greater in patients with phasic DO and BOO, and correlated with P2X3 expression, suggesting beta-3 AR plays an important role in this specific OAB patient subtype. Source of Funding: none

Display Omitted Human disease network (HDN) using disease codes in claims data.HDN consists of nodes for disease codes and edges for disease-disease associations.Human disease network shows the relationships between diseases or disease groups.Disease-disease associations can be classified according to underlying mechanisms.Human disease network provides new insights into disease-disease associations. ObjectiveTo investigate disease-disease associations by conducting a network analysis using Korean nationwide claims data. MethodsWe used the claims data from the Health Insurance Review and Assessment Service-National Patient Sample for the year 2011. Among the 2049 disease codes in the claims data, 1154 specific disease codes were used and combined into 795 representative disease codes. We analyzed for 381 representative codes, which had a prevalence of >0.1%. For disease code pairs of a combination of 381 representative disease codes, P values were calculated by using the ź2 test and the degrees of associations were expressed as odds ratios (ORs). ResultsFor 5515 (7.62%) statistically significant disease-disease associations with a large effect size (OR5), we constructed a human disease network consisting of 369 nodes and 5515 edges. The human disease network shows the distribution of diseases in the disease network and the relationships between diseases or disease groups, demonstrating that diseases are associated with each other, forming a complex disease network. We reviewed 5515 disease-disease associations and classified them according to underlying mechanisms. Several disease-disease associations were identified, but the evidence of these associations is not sufficient and the mechanisms underlying these associations have not been clarified yet. Further research studies are needed to investigate these associations and their underlying mechanisms. ConclusionHuman disease network analysis using claims data enriches the understanding of human diseases and provides new insights into disease-disease associations that can be useful in future research.

Background Cigarette smoking is a risk factor for cardiovascular disease (CVD) and has both beneficial and harmful effects in CVD. We hypothesized that weight gain following smoking cessation does not attenuate the CVD mortality of smoking cessation in the general Korean population. Methods Study subjects comprised 2.2% randomly selected patients from the Korean National Health Insurance Corporation, between 2002 and 2013. We identified 61,055 subjects who were classified as current smokers in 2003-2004. After excluding 21,956 subjects for missing data, we studied 30,004 subjects. We divided the 9,095 ex-smokers into two groups: those who gained over 2 kg (2,714), and those who did not gain over 2 kg (6,381, including weight loss), after smoking cessation. Cox proportional hazards regression models were used to estimate the association between weight gain following smoking cessation and CVD mortality. Results In the primary analysis, the hazard ratios of all-cause deaths and CVD deaths were assessed in the three groups. The CVD risk factors and Charlson comorbidity index adjusted hazard ratios (aHRs) for CVD deaths were 0.80 (95% confidence interval [CI], 0.37 to 1.75) for ex-smokers with weight gain and 0.80 (95% CI, 0.50 to 1.27) for ex-smokers with no weight gain, compared to one for sustained smokers. The associations were stronger for events other than mortality. The aHRs for CVD events were 0.69 (95% CI, 0.54 to 0.88) and 0.81 (95% CI, 0.70 to 0.94) for the ex-smokers with and without weight gain, respectively. Conclusion Although smoking cessation leads to weight gain, it does not increase the risk of CVD death.

Abuse of the hallucinogenic drug ketamine promotes the development of lower urinary tract symptoms that resemble interstitial cystitis. The pathophysiology of ketamine-induced cystitis (KC) is largely unknown and effective therapies are lacking. Here, using a KC rat model, we show the therapeutic effects of human umbilical cord-blood (UCB)-derived mesenchymal stem cells (MSCs). Daily injection of ketamine to Sprague-Dawley rats for 2-weeks resulted in defective bladder function, indicated by irregular voiding frequency, increased maximum contraction pressure, and decreased intercontraction intervals and bladder capacity. KC bladders were characterized by severe mast-cell infiltration, tissue fibrosis, apoptosis, upregulation of transforming growth factor-β signaling related genes, and phosphorylation of Smad2 and Smad3 proteins. A single administration of MSCs (1 × 106) into bladder tissue not only significantly ameliorated the aforementioned bladder voiding parameters, but also reversed the characteristic histological and gene-expression alterations of KC bladder. Treatment with the antifibrotic compound N-acetylcysteine also alleviated the symptoms and pathological characteristics of KC bladder, indicating that the antifibrotic capacity of MSC therapy underlies its benefits. Thus, this study for the first-time shows that MSC therapy might help to cure KC by protecting against tissue fibrosis in a KC animal model and provides a foundation for clinical trials of MSC therapy.

Background An activity tracker combined with a smartphone application (smartcare) may help people track and receive feedback on their own activities. However, activity trackers themselves generally fail to drive long-term sustained engagement for a majority of users. One potential strategy for increasing the effectiveness of smartcare is through the use of incentives. The purpose of this pilot randomized trial is to test the feasibility of our intervention and to assess the extent to which smartcare with or without financial incentives can increase physical activity levels and reduce weight over a 12-week period. Methods/design This study employs a three-arm, open-label randomized controlled trial design: control (standard basic education), smartcare, and smartcare plus financial incentives. Male university students with body mass index ≥ 27 are enrolled. Our primary and secondary endpoints are the amount of weight loss and the level of physical activity respectively. The weight loss goal is 3% of baseline at week 4, 5% at week 8, and 7% at week 12. The daily physical activity goal was individualized according to the participants' weight. Process incentives are accumulated when participants met daily physical activity goals, and outcome incentives are provided when they met weight reduction goals. Discussion Given the global increase in physical inactivity and obesity, there is a growing need for effective, scalable, and affordable health promotion strategies. Our proof-of-concept study will provide the evidence for the combination of rising health promotion technology of activity trackers and smartphone applications with the modern concept of behavioral economics using financial incentives.

Background: The relationship between economics and health has been of great interest throughout the years. The accumulated data is not sufficient enough to carry out long-term studies from the viewpoint of morbidity, although Korea National Health and Nutrition Examination Survey (KNHANES) was carried out yearly since 1998 in Korea. Thus, we investigated the effect of the 2008 global economic crisis on health indicators of Korea. Methods: Health indicators were selected by paired t-test based on 2007 and 2009 KNHANES data. Age, gender, body mass index (BMI), smoking, drinking, exercise, education, income, working status, and stress were used as confounding factors, which were analyzed with logistic and probit analyses. Validation was done by comparing gross domestic product (GDP) growth rates and probit analyses results of 2007–2012 KNHANES data. Results: Among several health indicators, the prevalence of hypertension and stress perception was higher after the economic crisis. Factors related with higher hypertension prevalence include older age, male gender, higher BMI, no current tobacco use, recent drinking, lower education levels, and stress perception. Factors related with more stress perception were younger age, female gender, current smoking, lower education levels, and lower income. GDP growth rates, a macroeconomic indicator, are inversely associated with hypertension prevalence with a one-year lag, and also inversely associated with stress perception without time lag. Conclusion: The economic crisis increased the prevalence of hypertension and stress perception. In the case of GDP growth rate change, hypertension was an inversely lagging indicator and stress perception was an inverselyrelated coincident indicator.

Purpose We aimed to assess the patient-reported outcome (PRO) and efficacy of add-on low-dose antimuscarinic therapy in over-active bladder (OAB) patients with suboptimal response to 4-week treatment with beta 3 agonist monotherapy (mirabegron, 50 mg). Materials and methods We enrolled OAB patients with 4-week mirabegron (50 mg) treatment if the patients' symptoms improved, but not to a satisfactory extent (patient perception of bladder condition [PPBC] ≥4). Enrolled patients had 8-week low-dose antimuscarinics add-on therapy (propiverine HCl, 10 mg). Patients recorded 3-day voiding diary at screening, enrollment (after 4 weeks of mirabegron monotherapy) and after 8 weeks of add-on therapy. We assessed the change of PRO (PPBC) as a primary end point and the efficacy of add-on therapy (change of frequency, urgency, urinary urgency incontinence [UUI] based on voiding diary) as a secondary end point. Results Thirty patients (mean age, 62.3±12.8 years; mean symptom duration, 16.0±12.3 months) were finally enrolled in the study. The mean PPBC value was 4.3±0.4 after mirabegron monotherapy, and decreased to 3.2±1.0 after 8-week add-on therapy. The mean urinary frequency decreased from 10.1±3.1 to 8.8±3, the mean number of urgency episodes decreased from 3.6±1.6 to 1.8±1.2 and the number of urgency incontinence episodes decreased from 0.7±1.0 to 0.2±0.5 after add-on therapy. No patients had event of acute urinary retention and three patients complained of mild dry mouth after add-on therapy. Conclusions Add-on therapy of low-dose antimuscarinics exhibits good efficacy and safety in patients with suboptimal response after 4-week of mirabegron (50 mg) monotherapy.

Background Cardiovascular disease (CVD) has become the most common cause of mortality and morbidity worldwide. Health screening is associated with higher outpatient visits for detection and treatment of CVD-related diseases (diabetes mellitus, hypertension, and dyslipidemia). We examined the association between health screening, health utilization, and economic status. Methods A sampled cohort database from the National Health Insurance Corporation was used. We included 306,206 participants, aged over 40 years, without CVD (myocardial infarction, stroke, and cerebral hemorrhage), CVD-related disease, cancer, and chronic renal disease. The follow-up period was from January 1, 2003 through December 31, 2005. Results Totally, 104,584 participants received at least one health screening in 2003–2004. The odds ratio of the health screening attendance rate for the five economic status categories was 1.27 (95% confidence interval [CI], 1.24 to 1.31), 1.05 (95% CI, 1.02 to 1.08), 1, 1.16 (95% CI, 1.13 to 1.19) and 1.50 (95% CI, 1.46 to 1.53), respectively. For economic status 1, 3, and 5, respectively, the diagnostic rate after health screening was as follows: diabetes mellitus: 5.94%, 5.36%, and 3.77%; hypertension: 32.75%, 30.16%, and 25.23%; and dyslipidemia: 13.43%, 12.69%, and 12.20%. The outpatient visit rate for attendees diagnosed with CVD-related disease was as follows for economic status 1, 3, and 5, respectively: diabetes mellitus: 37.69%, 37.30%, and 43.70%; hypertension: 34.44%, 30.09%, and 32.31%; and dyslipidemia: 18.83%, 20.35%, and 23.48%. Conclusion Thus, higher or lower economic status groups had a higher health screening attendance rate than the middle economic status group. The lower economic status group showed lower outpatient visits after screening, although it had a higher rate of CVD diagnosis.