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Georg Deutsch,1 Hrishikesh Deshpande,1 H Henry Lai,2 Jason J Kutch,3 Timothy J Ness4 1Department of Radiology, University of Alabama at Birmingham, Birmingham, AL, USA; 2Division of Urologic Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA; 3Division of Biokinesiology and Physical Therapy, University of Southern California, Los Angeles, CA, USA; 4Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, AL, USACorrespondence: Timothy J NessDepartment of Anesthesiology, University of Alabama at Birmingham, BMR2-208; 901 19th St. S, Birmingham, AL, 35205, USATel +1 205-975-9643Fax +1 205-934-7437Email tness@uabmc.eduPurpose: Fibromyalgia is a common co-morbidity in patients with interstitial cystitis/bladder pain syndrome. Quantitative sensory testing measures and regional cerebral blood flow measures have been noted to differ from healthy controls in both subjects with fibromyalgia and those with interstitial cystitis when studied independently. The present study examined such measures in subjects with the diagnosis of interstitial cystitis both with and without the co-diagnosis of fibromyalgia to determine whether differences in these measures may be associated with co-morbidity.Patients and Methods: Female subjects with the diagnosis of interstitial cystitis with (n = 15) and without (n = 19) the co-diagnosis of fibromyalgia as well as healthy control subjects (n = 41) underwent quantitative sensory testing. A subset of these patients (9 with and 9 without fibromyalgia) underwent brain perfusion studies using arterial spin labeled functional magnetic resonance imaging. An analysis was performed of absolute regional cerebral blood flow of regions-of-interest when experiencing a full bladder compared with an empty bladder.Results: Subjects with both interstitial cystitis and fibromyalgia were more hypersensitive than those without fibromyalgia as well as healthy controls in most sensory measures except heat. Subjects with interstitial cystitis, but no fibromyalgia, differed from healthy controls only in toleration of the ischemic forearm task. Other co-morbidities were more common in those subjects with both interstitial cystitis and fibromyalgia. Bladder fullness was associated with significantly greater whole brain gray matter blood flow in subjects with interstitial cystitis and fibromyalgia when compared with that of subjects with interstitial cystitis without fibromyalgia. Examination of regional cerebral blood flow in individual regions-of-interest demonstrated statistically significant differences between the subjects with interstitial cystitis with and those without fibromyalgia bilaterally in the thalamus, amygdala and hippocampus, as well as the right prefrontal cortex and greater responsiveness to changes in bladder fullness in the insula.Conclusion: Quantitative sensory testing and brain perfusion data support that there are two phenotypes of interstitial cystitis patients, which can be differentiated by a co-diagnosis of fibromyalgia. This may affect responsiveness to treatment and suggest the utility of stratifying interstitial cystitis patients according to their co-morbidities.Keywords: arterial spin labelling, fMRI, interstitial cystitis, QST

PurposeWe evaluated and identified baseline factors associated with change in health related quality of life among patients with interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome.Materials and methodsA total of 191 men and 233 women with interstitial cystitis/bladder pain syndrome or chronic prostatitis/chronic pelvic pain syndrome (collectively referred to as urologic chronic pelvic pain syndrome) were followed for 12 months with bimonthly completion of the Short Form 12 to assess general mental and physical health related quality of life, and with biweekly assessment of condition specific health related quality of life using the Genitourinary Pain Index. A functional clustering algorithm was used to classify participants as improved, stable or worsened for each health related quality of life measure. Ordinal logistic regression was used to determine baseline factors associated with change.ResultsPhysical health related quality of life improved in 22% of the participants, mental health related quality of life improved in 25% and condition specific health related quality of life improved in 47%. Better baseline physical health related quality of life, older age and the presence of nonurological symptoms were associated with lower likelihood of improvement in physical health related quality of life. Better baseline mental health related quality of life, female sex, and greater baseline depression and stress were associated with a lower likelihood of improvement in mental health related quality of life. Better baseline condition specific health related quality of life and more severe baseline urologic chronic pelvic pain syndrome pain symptoms were associated with a lower likelihood of improvement in condition specific health related quality of life.ConclusionsWhile several nonurologic chronic pelvic pain syndrome factors influenced the trajectory of general health related quality of life over time, only condition specific baseline health related quality of life and urologic chronic pelvic pain syndrome symptoms were associated with urologic chronic pelvic pain syndrome specific health related quality of life change. Significant differences in how urologic chronic pelvic pain syndrome impacts various aspects of health related quality of life suggest a multidisciplinary approach to assessment and treatment of these patients.

Abstract: Pain clinical trials are notoriously complex and often inefficient in demonstrating efficacy, even for known efficacious treatments. A major issue is the difficulty in the a priori identification of specific phenotypes to include in the study population. Recent work has identified the extent of widespread pain as an important determinant of the likelihood of response to therapy, but it has not been tested in clinical trials for the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS). We explored this hypothesis using data from 3 previously published trials testing treatments for IC/BPS, which suggested modest benefits but did not meet a priori primary outcome statistical significance criteria. Importantly, these studies also collected symptom questionnaire data that allowed us to retrospectively identify participants with and without widespread pain. Analyzing the treatment by the degree of widespread pain revealed a difference in outcome and statistical significance level for each trial. Participants with predominately local pain (ie, limited widespread pain symptoms) responded to therapy targeting local symptoms, whereas those with widespread pain did not. Alternatively, participants with widespread pain beyond their local pelvic pain responded to more centrally acting treatments. Our results suggest that differentiating patients based on widespread vs more localized pain is a key consideration for designing future clinical trials for conditions with variable pain profiles, such as IC/BPS and potentially other pain-based syndromic disorders., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

The tumor protein D52 (TPD52) gene encodes a proto-oncogene protein associated with various medical conditions, including breast and prostate cancers. It plays a role in multiple biological pathways such as cell growth, differentiation, and apoptosis. The function of TPD52 in lipid droplet biosynthesis has been investigated in vitro. However, its precise role in lipid metabolism in animal models is not fully understood. To investigate the functions of TPD52 in vivo, we performed a conditional TPD52 protein expression analysis using a Tet-off transgenic system to establish conditionally expressed Tpd52 transgenic zebrafish. The effect of Tpd52 on lipogenesis was assessed using various methods, including whole-mount Oil Red O staining, histological examination, and measurement of inflammatory markers and potential targets using real-time quantitative polymerase chain reaction and immunoblotting in Tpd52 fish. Zebrafish with increased Tpd52 levels exhibited notable weight gain and the enlargement of fat deposits, which were mainly attributed to an increase in the volume of adipocytes. Moreover, Tpd52 overexpression was correlated with the triggering of the adipocyte differentiation signaling pathway. During adipocytic differentiation in response to nutrient status, our observations revealed adipogenesis, nonalcoholic fatty liver disease, and metabolic cardiomyopathy (MCM) in Tpd52 transgenic zebrafish. To gain a deeper understanding of the contribution of these proteins to the regulation of cellular growth, we investigated the expression of their corresponding genes and proteins in zebrafish. In the present study, the activated protein kinase pathway was identified as the primary target of TPD52. Adult Tpd52 zebrafish showed increased lipid accumulation, resulting in the development of visceral obesity, nonalcoholic fatty liver disease, and MCM. These findings strongly suggest that TPD52 actively contributes to adipose tissue expansion and its subsequent effects. This investigation provides compelling evidence that Tpd52 facilitates adipocyte development and related metabolic comorbidities in zebrafish., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Predictors for coronavirus disease 2019 (COVID-19)-specific and non-COVID-19-specific deaths have not been extensively studied. This cohort study in Taiwan investigated predictors for COVID-19-specific and non-COVID-19-specific deaths among hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. From January to July 2022, 2196 COVID-19 patients at Taipei City Hospital were consecutively recruited in this cohort study. Among the 175 deceased COVID-19 patients, 147 (84.0%) and 28 (16.0%) had COVID-19-specific and non-COVID-19-specific deaths, respectively. After controlling for other covariates, multinomial logistic regressions showed that age ≥ 65 was significantly associated with higher risks for both COVID-19-specific, adjusted odds ratio (AOR) = 6.21; and non-COVID-19-specific deaths (AOR = 6.06). Fully vaccinated individuals (AOR = 0.50) and Paxlovid recipients (AOR = 0.45) had lower COVID-19-specific death risks, while comorbid cancer or end-stage renal disease patients faced higher risks of non-COVID-19-specific deaths. Our study findings suggest that vaccination and Paxlovid treatment are crucial for reducing SARS-CoV-2-specific mortalities, while comorbid patients need careful monitoring to reduce non-COVID-19-specific deaths., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aims: The Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) is undertaking a new cohort study in LURN II including cases and controls., Methods: This new cohort was enrolled to specifically study urinary urgency and urgency urinary incontinence, lower urinary tract symptoms (LUTSs) that are often difficult to treat due to a lack of understanding of their phenotypes and pathophysiologies., Results: This paper will focus on the motivation for the second iteration of LURN and highlight the new research techniques and plans for more thorough phenotyping of this population., Conclusions: This paper will outline the gaps in understanding in treating LUTSs, specifically urinary urgency., (© 2024 The Author(s). Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Objectives: This study aimed to analyse the value of pre-operative 18 F-fluorodeoxyglucose positron emission tomography (PET)-computed tomography that can predict tumour pathological complete response, tumour histology grade, overall survival, and recurrence-free survival in patients with locally advanced oesophageal squamous cell carcinoma who underwent neoadjuvant chemoradiotherapy (NCRT) followed by surgery., Methods: We retrospectively reviewed the cases of patients with locally advanced oesophageal squamous cell carcinoma undergoing NCRT followed by surgery. Patients who did not undergo PET within 3 months of surgery were excluded. We set a pre-operative PET maximum standardised uptake value (SUVmax) of > 5 as the threshold and classified the patients into two groups. We analysed the tumour response and histology grade, and compared the overall survival and recurrence-free survival between the two groups., Results: This cohort included 92 patients with oesophageal squamous cell carcinoma who underwent NCRT followed by surgery; 49 patients had a pre-operative PET SUVmax < 5, and 43 patients had a pre-operative PET SUVmax > 5. The patients' pre-operative PET SUVmax correlated with tumour histology, ypT stage, and tumour response. Patients with a pre-operative SUVmax < 5 had better 2-year-overall survival (78% vs. 62%, P < 0.05) and 2-year recurrence-free survival (62% vs. 34%, P < 0.05) than those with a pre-operative SUV > 5., Conclusions: Pre-operative SUVmax may be useful to predict tumour response, survival, and recurrence in patients with locally advanced oesophageal squamous cell carcinoma who undergo NCRT followed by surgery., (© 2024. The Author(s).)

Objective: To explore clinical efficacy of F-type forceps for assisted reduction in femoral shaft fracture reduction., Methods: Forty-five patients with femoral shaft fracture treated with intramedullary nail and internal fixation from January 2019 to December 2021 were retrospectively analyzed and divided into two groups according to different reduction methods. In observation group, there were 21 patients, included 15 males and 6 females, aged from 27 to 92 years old with an average of (53.38±18.81) years old;9 patients on the left side, 12 patients on the right side;7 patients were type A, 8 patients were type B and 6 patients were type C according to AO fracture classification;the time from injury to operation ranged from 7 to 13 days with an average of (4.62±3.34) days;reduction was assisted by F-shaped forceps. In control group, there were 24 patients, including 17 males and 7 females, aged from 20 to 92 years old with an average of (51.96±20.43) years old;12 patients on the left side, 12 patients on the right side;11 patients were type A, 8 patients were type B and 5 patients were type C according to AO fracture classification;the time from injury to operation ranged from 2 to 13 days with an average of (6.29±3.04) days;traditional reset mode was adopted. Operative time, intraoperative blood loss, intraoperative fluoroscopy times, intraoperative open reduction ratio, clinical healing time of fracture, postoperative complications, hospital stay, hospital cost and Lysholm score of knee joint at 6 and 12 months after surgery were compared between two groups to evaluate clinical effect., Results: All patients were followed up for 12 to 24 months with an average of (16.60±3.45) months. In observation group, operative time, intraoperative blood loss, intraoperative fluoroscopy times, open reduction cases, and clinical healing time of fractures were (58.19±7.93) min, (88.10±44.45) ml, (25.29±5.54) times, 0 case, (4.76±0.77) months, respectively;while in control group was (79.33±22.94) min, (222.92±144.45) ml, (47.46±26.25) times, 5 cases, (7.13±1.80) months, and the difference between two groups were statistically significant ( P <0.05). There were no significant difference in postoperative complications, length of stay and hospitalization cost between two groups ( P >0.05). At 6 months after surgery, Lysholm score of knee joint in observation group (88.62±4.48) was better than that in control group (79.21±8.91) ( F =21.948, P =0.000). There were no significant difference in support use, pain and squat score between two groups ( P >0.05). At 12 months after surgery, Lysholm scores of stair climbing and pain in observation group were (9.62±1.20) and (19.76±1.92), which were better than those in control group (7.83±2.04) and (21.88±2.88) ( P <0.05). There were no significant difference in scores and total scores of other items between two groups ( P >0.05)., Conclusion: Compared with traditional reduction method, F-type forceps instrument could shorten operation time, reduce intraoperative blood loss, reduce intraoperative fluoroscopy times, accelerate clinical healing of fracture, and promote earlier functional recovery of knee joint.

Background: Pediatric patients with short bowel syndrome (SBS) often require long-term parenteral nutrition and intravenous fluid support (PN) until enteral autonomy (EA). However, long-term PN accounts for many complications. We aimed to investigate the outcome and predictors of EA in these patients., Material and Methods: This retrospective observational study was conducted in Children's Medical Center, Chang Gung Memorial Hospital, a tertiary hospital in Northern Taiwan. Twenty-four patients afflicted with short bowel syndrome between 2002 and 2021 were included. Demographics, operation results, follow-up status, complications, and outcomes were reviewed., Results: Among the 24 patients, 14 were males (58%). The median age at bowel resection was 3 days (IQR, 1.3 to 28.8 days). The most common etiologies were total/subtotal intestinal aganglionosis (TIA) (N=6) and malrotation with midgut volvulus (N=6). The median length of the residual small intestine was 25cm (IQR, 7.8 to 71.3cm). Ten (41.7%) had preserved ileocecal valve, and 14 (58.3%) had colon-in-continuity. Intestinal failure-associated liver disease (IFALD) occurred in 14 patients (58.3%), but none had advanced disease. Seven (29.2%) patients achieved enteral autonomy after 10.1±7.3 months. Five patients (21%) expired due to sepsis. Logistic regression and Kaplan-Meier analysis showed the predictors of enteral autonomy were remaining-to-expected small bowel length ratio > 25% and the absence of IFALD., Conclusions: In this pediatric short bowel syndrome study, enteral autonomy was achieved in 29% after a mean PN duration of 10 months. The remaining-to-expected small bowel length ratio at bowel resection was the most critical predictor of enteral autonomy., Competing Interests: Declaration of Competing Interest The authors declare no ethical or financial conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To assess accuracy of self-reported stone events in a large clinical trial by adjudication against the weight of documentation for spontaneous stone passage or surgical intervention., Methods: Participants in the Prevention of Urinary Stones with Hydration (PUSH) trial were randomized to a multi-component behavioral intervention or control arm to increase and maintain high fluid intake. The primary endpoint was urinary stone events including symptomatic stone passage or procedural intervention. An independent adjudication committee blinded to randomization assignments reviewed all events. Confirmed clinical stone events required typical stone symptoms and documentation of stone passage (eg, via photograph, clinical record) and/or surgical intervention. Events with typical symptoms and self-described stone passage but without objective documentation of passage were also considered as meeting the primary endpoint and classified separately as patient-reported passage. Non-events did not meet either criteria., Results: At time of this blinded analysis, a total of 1658 participants were randomized and had a median follow-up of 19 months. Self-reported stone events (n = 217) were adjudicated by the committee as either confirmed clinical events (134; 61.8%), patient-reported passage (71; 32.7%), or non-events (12; 5.5%). Confirmed clinical events consisted of stone passage in 66/134 and procedural interventions in 68/134 (53 for symptoms and 15 without symptoms)., Conclusion: Rigorous adjudication revealed that self-reported stone events in the PUSH trial overwhelmingly represented clinically documented passage, surgical intervention, and patient-reported passage outside healthcare settings, with only 5.5% failing to satisfy adjudication criteria. Similar adjudication and classification processes warrant consideration for implementation in future stone trials., Clinical Trials Registration: NCT03244189., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lai: Consultant for Medtronic, Neuspera, Allergan, Teva. Reese: Disclosures related to the submitted work: Associate editor at the American Journal of Kidney Diseases; disclosures outside of the submitted work: investigator-initiated grants from Merck and AbbVie to the University of Pennsylvania to support research on transplantation of HCV-infected organs into uninfected recipients, followed by antiviral treatment; investigator-initiated grants from CVS Caremark and Merck to the University of Pennsylvania to support research on medication adherence (focus: statins); consulting with COllaborative Healthcare Research & Data Analytics (COHRDATA) on epidemiology of medications to improve laboratory parameters including potassium among dialysis patients. Scales: Scientific Advisory Board for Lilac Therapeutics. Tasian: Scientific Advisory Board for Novo Nordisk and Alnylam Pharmaceuticals. No other potentially relevant disclosures were reported., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Our objective was to investigate structural changes in brain white matter tracts using diffusion tensor imaging (DTI) in patients with overactive bladder (OAB)., Materials and Methods: Treatment-seeking OAB patients and matched controls enrolled in the cross-sectional case-control LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network) Neuroimaging Study received a brain DTI scan. Microstructural integrity of brain white matter was assessed using fractional anisotropy (FA) and mean diffusivity. OAB and urgency urinary incontinence (UUI) symptoms were assessed using the OAB Questionnaire Short-Form and International Consultation on Incontinence Questionnaire-Urinary Incontinence. The Lower Urinary Tract Symptoms Tool UUI questions and responses were correlated with FA values., Results: Among 221 participants with evaluable DTI data, 146 had OAB (66 urinary urgency-only without UUI, 80 with UUI); 75 were controls. Compared with controls, participants with OAB showed decreased FA and increased mean diffusivity, representing greater microstructural abnormalities of brain white matter tracts among OAB participants. These abnormalities occurred in the corpus callosum, bilateral anterior thalamic radiation and superior longitudinal fasciculus tracts, and bilateral insula and parahippocampal region. Among participants with OAB, higher OAB Questionnaire Short-Form scores were associated with decreased FA in the left inferior fronto-occipital fasciculus, P < .0001. DTI differences between OAB and controls were driven by the urinary urgency-only (OAB-dry) but not the UUI (OAB-wet) subgroup., Conclusions: Abnormalities in microstructural integrity in specific brain white matter tracts were more frequent in OAB patients. More severe OAB symptoms were correlated with greater degree of microstructural abnormalities in brain white matter tracts in patients with OAB., Trial Registration: ClinicalTrials.gov: NCT02485808.

Purpose: To study the effectiveness of federated learning in in vitro fertilization on embryo evaluation tasks., Methods: This is a retrospective cohort analysis. Two datasets were used in this study. The ploidy status dataset consisted of 10,065 embryo records, 3760 treatments, and 2479 infertile couples from 5 hospitals. The clinical pregnancy dataset consisted of 4495 embryo records, 4495 treatments, and 3704 infertile couples from 4 hospitals. Federated learning and the gradient boosting decision tree algorithm were utilized for modeling., Results: On the ploidy status dataset, the areas under the receiver operating characteristic curves of our model trained with federated learning were 71.78%, 73.10%, 69.39%, 69.72%, and 73.46% for 5 hospitals respectively, showing an average increase of 2.5% compared to those of our model trained without federated learning. On the clinical pregnancy dataset, the areas under the receiver operating characteristic curves of our model trained with federated learning were 72.03%, 56.77%, 61.63%, and 58.58% for 4 hospitals respectively, showing an average increase of 3.08%., Conclusions: Federated learning can improve data privacy and data security and meanwhile improve the performance of embryo selection tasks by leveraging data from multiple sources. This study demonstrates the effectiveness of federated learning in embryo evaluation, and the results show the promise for future application., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: To explore the correlation between mitochondrial quantity and the blastocyst development timeline as well as their respective contributions to early pregnancy., Methods: A retrospective study was conducted using a dataset comprising 2,633 embryos that underwent preimplantation genetic testing for aneuploidy (PGT-A) between January 2016 and December 2023. The study was divided into three subsets to address distinct aspects: the representativeness of a single trophectoderm (TE) biopsy for mitochondrial quantity (n=43), the correlation between morphokinetic features and mitochondrial quantity (n=307), and the association analysis among mitochondrial quantity, blastocyst timeline factor, and reproductive outcomes (n=2,283). Distribution assessment of mitochondrial quantity across an individual blastocyst involved the identification within multiple biopsies and spent culture media. Timeline evaluation included correlating mitochondrial quantity with time-lapse datasets. Finally, multivariate logistic regression models, incorporating potential effectors alongside mitochondrial quantity, were employed to analyze their respective contributions to early pregnancy endpoints., Results: Of distribution assessment, mitochondrial quantity exhibited an even distribution across the entire trophectoderm (Spearman's ρ=0.82), while no detectable mtDNAs in the corresponding spent culture media. Then the timeline correlation study revealed significant association between mitochondrial quantity and blastocyst features of both the day of expanded blastocyst formation (95% Confidence intervals, CIs: 0.27~4.89, p=0.03) and the timing of expanded blastocyst formation (tEB) (95% CIs: -0.24~-0.01, p=0.04) in the regression model, indicating a strong dependency between mitochondrial quantity and the blastocyst development timeline. For the contribution to early pregnancy, multivariate logistic regression models showed that the day of expanded blastocyst formation contributed to four endpoints persistently: positive for HCG (odd ratio, OR: 0.71, p=0.006), gestational sac (OR: 0.78, p=0.04), fetal heartbeat (OR: 0.71, p=0.004), and progression to 14 weeks (OR: 0.69, p=0.002). Contrastingly, no notable correlation was observed between the mitochondrial quantity and these endpoints., Conclusions: Strong interaction was observed between mitochondrial quantity and the blastocyst timeline, particularly the timing of expanded blastocyst formation. It suggests that the primary determinant influencing pregnancy outcomes lies in the time-dependent parameter of blastocyst rather than in the specific mitochondrial quantity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chuang, Chou, Kuan, Liu, Kao, Wu, Lai, Hsieh, Liang, Chen and Chen.)

Background: Structured Problem Solving (SPS) is a patient-centered approach to promoting behavior change that relies on productive collaboration between coaches and participants and reinforces participant autonomy. We aimed to describe the design, implementation, and assessment of SPS in the multicenter Prevention of Urinary Stones with Hydration (PUSH) randomized trial., Methods: In the PUSH trial, individuals with a history of urinary stone disease and low urine output were randomized to control versus a multicomponent intervention including SPS that was designed to promote fluid consumption and thereby prevent recurrent stones. We provide details specifically about training and fidelity assessment of the SPS coaches. We report on implementation experiences related to SPS during the initial conduct of the trial., Results: With training and fidelity assessment, coaches in the PUSH trial applied SPS to help participants overcome barriers to fluid consumption. In some cases, coaches faced implementation barriers such as variable participant engagement that required tailoring their work with specific participants. The coaches also faced challenges including balancing rapport with problem solving, and role clarity for the coaches., Conclusions: We adapted SPS to the setting of kidney stone prevention and overcame challenges in implementation, such as variable patient engagement. Tools from the PUSH trial may be useful to apply to other health behavior change settings in nephrology and other areas of clinical care., Trial Registration: ClinicalTrials.gov Identifier NCT03244189., (© 2024. The Author(s).)

Background: Early diagnosis and surgical intervention for midgut malrotation with bowel obstruction are crucial. We aimed to identify risk factors for adverse outcomes in infants with midgut malrotation and to develop a prediction model., Methods: We reviewed the operation records of infants surgically diagnosed with midgut malrotation at Chang Gung Children's Medical Center between January 2000 and December 2020. Patients were classified into the poor-outcome group (PO) if they underwent bowel resection or experienced mortality; all others were categorized as the favorable-outcome group (FO). Data on demographics, initial presentations, laboratory results, radiographic or sonographic findings, maternal conditions, and outcomes were collected and analyzed. Fisher's exact test, the independent sample t-test, and the Mann-Whitney test were utilized for comparative analysis when suitable., Results: The study included 103 infants. Eleven were in the PO group, and 92 were in the FO group. Initial presentations such as respiratory distress, poor activity, and shock status were notably more prevalent in the PO group. The INR, hemoglobin, HCO 3 , base excess, and aspartate transaminase values showed significant variation between the two groups. Multivariate analysis identified that lower hemoglobin (OR 0.677, p = 0.043) and higher AST (OR 1.036, p = 0.044) were independent predictors of adverse outcomes. An AST/Hb ratio of <3.78 demonstrated a high negative predictive value (98.6%) for an adverse outcome in midgut malrotation., Conclusions: Prompt diagnosis and surgical treatment of midgut malrotation are vital to prevent bowel resection or mortality. The independent predicting factors for poor outcomes include low hemoglobin and elevated AST levels., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Recently, there has been increasing emphasis on the gonadotoxic effects of cancer therapy in prepubertal boys. As advances in oncology treatments continue to enhance survival rates for prepubertal boys, the need for preserving their functional testicular tissue for future reproduction becomes increasingly vital. Therefore, we explore cutting-edge strategies in fertility preservation, focusing on the cryopreservation and transplantation of immature testicular tissue as a promising avenue. The evolution of cryopreservation techniques, from controlled slow freezing to more recent advancements in vitrification, with an assessment of their strengths and limitations was exhibited. Detailed analysis of cryoprotectants, exposure times, and protocols underscores their impact on immature testicular tissue viability. In transplantation strategy, studies have revealed that the scrotal site may be the preferred location for immature testicular tissue grafting in both autotransplantation and xenotransplantation scenarios. Moreover, the use of biomaterial scaffolds during graft transplantation has shown promise in enhancing graft survival and stimulating spermatogenesis in immature testicular tissue over time. This comprehensive review provides a holistic approach to optimize the preservation strategy of human immature testicular tissue in the future., (© 2024. The Author(s).)

Purpose: To study the effectiveness of whole-scenario embryo identification using a self-supervised learning encoder (WISE) in in vitro fertilization (IVF) on time-lapse, cross-device, and cryo-thawed scenarios., Methods: WISE was based on the vision transformer (ViT) architecture and masked autoencoders (MAE), a self-supervised learning (SSL) method. To train WISE, we prepared three datasets including the SSL pre-training dataset, the time-lapse identification dataset, and the cross-device identification dataset. To identify whether pairs of images were from the same embryos in different scenarios in the downstream identification tasks, embryo images including time-lapse and microscope images were first pre-processed through object detection, cropping, padding, and resizing, and then fed into WISE to get predictions., Results: WISE could accurately identify embryos in the three scenarios. The accuracy was 99.89% on the time-lapse identification dataset, and 83.55% on the cross-device identification dataset. Besides, we subdivided a cryo-thawed evaluation set from the cross-device test set to have a better estimation of how WISE performs in the real-world, and it reached an accuracy of 82.22%. There were approximately 10% improvements in cross-device and cryo-thawed identification tasks after the SSL method was applied. Besides, WISE demonstrated improvements in the accuracy of 9.5%, 12%, and 18% over embryologists in the three scenarios., Conclusion: SSL methods can improve embryo identification accuracy even when dealing with cross-device and cryo-thawed paired images. The study is the first to apply SSL in embryo identification, and the results show the promise of WISE for future application in embryo witnessing., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To develop evidence- and consensus-based clinical practice guidelines for management of high-tone pelvic floor dysfunction (HTPFD). High-tone pelvic floor dysfunction is a neuromuscular disorder of the pelvic floor characterized by non-relaxing pelvic floor muscles, resulting in lower urinary tract and defecatory symptoms, sexual dysfunction, and pelvic pain. Despite affecting 80% of women with chronic pelvic pain, there are no uniformly accepted guidelines to direct the management of these patients., Methods: A Delphi method of consensus development was used, comprising three survey rounds administered anonymously via web-based platform (Qualtrics XM) to national experts in the field of HTPFD recruited through targeted invitation between September and December 2021. Eleven experts participated with backgrounds in urology, urogynecology, minimally invasive gynecology, and pelvic floor physical therapy (PFPT) participated. Panelists were asked to rate their agreement with rated evidence-based statements regarding HTPFD treatment. Statements reaching consensus were used to generate a consensus treatment algorithm., Results: A total of 31 statements were reviewed by group members at the first Delphi round with 10 statements reaching consensus. 28 statements were reposed in the second round with 17 reaching consensus. The putative algorithm met clinical consensus in the third round. There was universal agreement for PFPT as first-line treatment for HTPFD. If satisfactory symptom improvement is reached with PFPT, the patient can be discharged with a home exercise program. If no improvement after PFPT, second-line options include trigger or tender point injections, vaginal muscle relaxants, and cognitive behavioral therapy, all of which can also be used in conjunction with PFPT. Onabotulinumtoxin A injections should be used as third line with symptom assessment after 2-4 weeks. There was universal agreement that sacral neuromodulation is fourth-line intervention. The largest identified barrier to care for these patients is access to PFPT. For patients who cannot access PFPT, experts recommend at-home, guided pelvic floor relaxation, self-massage with vaginal wands, and virtual PFPT visits., Conclusion: A stepwise approach to the treatment of HTPFD is recommended, with patients often necessitating multiple lines of treatment either sequentially or in conjunction. However, PFPT should be offered first line., Competing Interests: Financial Disclosure Michele Torosis is an advisor for Iota Bioscience and Exploramed Development. Kimberly Kenton reports receiving payment from Ethicon for expert witness testimony. Rhonda Kotarinos is a contributor to UpToDate. Erin Carey reports providing expert witness testimony unrelated to this work for McEwan, Martinez, Dukes & Hall, P.A.; BeytinMcLaughlin; Massy & Associates; Wallach; McBrideHall; and Davis Wright Tremaine, LLP. She received payments from Med IQ for providing education on endometriosis. She holds two patents held by UNC remote from commercialization. Neither is licensed and neither is evaluated or considered in this Delphi review. No payment, royalties, or honoraria were received or planned from them in the next 12 months: 1) PCT International PCT/US20/55816, a drug delivery system for vulvodynia symptoms in women; and 2) PCT/US2023/016013, a device for pelvic floor dysfunction in women. She received honoraria for Grand Rounds from LSU (5/2023) and USF (4/2023). She is an International Pelvic Pain Society Immediate past president. H. Henry Lai disclosed money was paid to his institution from the NIH and Metronic. He received payment from Neuspera. He has relationships with Astella, IronWood, BioHaven, Aquinox, Teva, and MicroGenDx. Jerry Lowder reports money was paid to their institution from the NIH-NIDDK. They also received payment as an expert witness. Melanie Meister reports receiving payment from AbbVie, Inc. A. Lenore Ackerman receives grant funding from Medtronic, Inc. and MicrogenDx. Dr. Ackerman is an advisor for AbbVie and Watershed Medical. The other authors did not report any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Lung transplantation is one of the most common treatment options for patients with end-stage chronic obstructive pulmonary disease. However, the choice between single and double lung transplantation for these patients remains a matter of debate. Therefore, we performed a systematic search of medical databases for studies on single lung transplantation, double lung transplantation, and chronic obstructive pulmonary disease., Methods: The rate ratio and hazard ratio of survival were analyzed. The meta-analysis included 15 case-control and retrospective registry studies., Results: The rate ratios of the 3-year survival (0.937 and P = 0.041) and 5-year survival (0.775 and P = 0.000) were lower for single lung transplantation than for double lung transplantation. However, the hazard ratio did not differ significantly between the two., Conclusions: Double lung transplantation was found to provide better benefits than single lung transplantation in terms of the long-term survival in patients with chronic obstructive pulmonary disease., (© 2024. The Author(s).)

Purpose: We sought to systematically review and summarize the peer-reviewed literature on urologic chronic pelvic pain syndrome flares, including their terminology, manifestation, perceived triggers, management and prevention strategies, impact on quality of life, and insights into pathophysiologic mechanisms, as a foundation for future empirical research., Materials and Methods: We searched 6 medical databases for articles related to any aspect of symptom exacerbations for interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome. A total of 1486 abstracts and 398 full-text articles were reviewed, and data were extracted by at least 2 individuals., Results: Overall, we identified 59 articles, including 36 qualitative, cross-sectional, or case-control; 15 cohort-based; and 8 experimental articles. The majority of studies described North American patients with confirmed diagnoses. "Flare" was a commonly used term, but additional terminology (eg, exacerbation) was also used. Most flares involved significant increases in pain intensity, but less data were available on flare frequency and duration. Painful, frequent, long-lasting, and unpredictable flares were highly impactful, even over and above participants' nonflare symptoms. A large number of perceived triggers (eg, diet, stress) and management/prevention strategies (eg, analgesics, thermal therapy, rest) were proposed by participants, but few had empirical support. In addition, few studies explored underlying biologic mechanisms., Conclusions: Overall, we found that flares are painful and impactful, but otherwise poorly understood in terms of manifestation (frequency and duration), triggers, treatment, prevention, and pathophysiology. These summary findings provide a foundation for future flare-related research and highlight gaps that warrant additional empirical studies.

Purpose: In patients with urologic chronic pelvic pain syndrome (UCPPS), the presence of widespread pain appears to identify a distinct phenotype, with a different symptom trajectory and potentially different response to treatment than patients with pelvic pain only., Materials and Methods: A 76-site body map was administered four times, at weekly intervals, to 568 male and female UCPPS participants in the MAPP Network protocol. The 76 sites were classified into 13 regions (1 pelvic region and 12 nonpelvic regions). The degree of widespread pain was scored from 0 to 12 based on the number of reported nonpelvic pain regions. This continuous body map score was regressed over other measures of widespread pain, with UCPPS symptom severity, and with psychosocial variables to measure level of association. These models were repeated using an updated body map score (0-12) that incorporated a threshold of pain ≥ 4 at each site., Results: Body map scores showed limited variability over the 4 weekly assessments, indicating that a single baseline assessment was sufficient. The widespread pain score correlated highly with other measures of widespread pain and correlated with worsened UCPPS symptom severity and psychosocial functioning. Incorporating a pain severity threshold ≥4 resulted in only marginal increases in these correlations., Conclusions: These results support the use of this 13-region body map in the baseline clinical assessment of UCPPS patients. It provides reliable data about the presence of widespread pain and does not require measurement of pain severity, making it relatively simple to use for clinical purposes., (© 2024 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Background: Early-stage esophageal cancer is treated using endoscopic submucosal dissection and esophagectomy. Field cancerization in patients with early-stage esophageal cancer affects treatment outcomes and causes synchronous or metachronous head and neck cancers. We hypothesized that esophagectomy could provide better overall and relapse-free survivals in patients with esophageal cancer and synchronous or metachronous head and neck cancer., Methods: We retrospectively identified patients with early esophageal squamous cell carcinoma and synchronous or metachronous head and neck cancers. We separated the patients into endoscopic submucosal dissection and esophagectomy groups to compare overall and relapse-free survivals., Results: The study included 106 patients, 25 of whom underwent endoscopic submucosal dissection and 81 underwent esophagectomy. Overall and relapse-free survivals did not show significant differences between the two groups for both synchronous and metachronous head and neck cancers., Conclusions: Endoscopic submucosal dissection could provide similar overall and relapse-free survivals in patients with esophageal cancer and synchronous or metachronous head and neck cancer., (© 2024. The Author(s).)

Importance: Physical health and psychological health represent modifiable factors in the causal pathway of lower urinary tract symptoms (LUTS)., Objectives: Understand the relationship between physical and psychological factors and LUTS over time., Study Design: Adult women enrolled in the Symptoms of Lower Urinary Tract Dysfunction Research Network observational cohort study completed the LUTS Tool and Pelvic Floor Distress Inventory, including urinary (Urinary Distress Inventory), prolapse (Pelvic Organ Prolapse Distress Inventory), and colorectal anal (Colorectal-Anal Distress Inventory) subscales at baseline, 3 months, and 12 months. Physical functioning, depression, and sleep disturbance were measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaires; relationships were assessed using multivariable linear mixed models., Results: Of 545 women enrolled, 472 had follow-up. Median age was 57 years; 61% and 78% reported stress urinary incontinence and overactive bladder, respectively; and 81% reported obstructive symptoms. The PROMIS depression scores were positively associated with all urinary outcomes (range, 2.5- to 4.8-unit increase per 10-unit increase in depression score; P < 0.01 for all). Higher sleep disturbance scores were associated with higher urgency, obstruction, LUTS Total Severity, Urinary Distress Inventory, and Pelvic Floor Distress Inventory (1.9- to 3.4-point increase per 10-unit increase, all P < 0.02). Better physical functioning was associated with less severe urinary symptoms except stress urinary incontinence (2.3- to 5.2-point decrease per 10-unit increase, all P < 0.01). All symptoms decreased over time; however, no association was detected between baseline PROMIS scores and trajectories of LUTS over time., Conclusions: Nonurologic factors demonstrated small to medium cross-sectional associations with urinary symptom domains, but no significant association was detected with changes in LUTS. Further work is needed to determine whether interventions targeting nonurologic factors reduce LUTS in women., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2023 American Urogynecologic Society. All rights reserved.)

Purpose: Overactive bladder (OAB) may be attributed to dysfunction in supraspinal brain circuits. Overactive bladder participants enrolled in the LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network) study reported sensations of urinary urgency during a bladder-filling paradigm while undergoing brain functional MRI to map supraspinal dysfunction., Materials and Methods: OAB participants and controls (CONs) completed 2 resting-state functional MRI scans following consumption of 350 mL water. Scans were conducted at fuller and emptier bladder states, interleaved with voiding. Urgency ratings (0-10) were assessed. Patterns of urgency during bladder filling were investigated using latent class trajectory models. Clusters of participants encompassing each pattern (ie, subtype) were derived from aggregated groups of OAB and CON independent of diagnosis., Results: Two distinct patterns of urgency trajectories were revealed: first subtype with OAB and CON who were unresponsive to bladder filling (OAB-1 and CON-1) and second highly responsive subtype predominantly containing OAB (OAB-2). OAB-2 participants scored significantly higher on urinary symptoms but not pain or psychosocial measures. Neuroimaging analyses showed change in urgency due to both bladder filling and voided volume related to multiple loci of brain network connectivity in OAB-2, and in some cases, different than OAB-1 and/or CON-1. Sensorimotor to dorsomedial/dorsolateral prefrontal connectivity mediated the relationship between stimulus (voided volume) and percept (urgency) in OAB-2., Conclusions: Our results reveal different OAB subtypes with latent class trajectory models of urgency ratings during natural bladder filling. Functional MRI revealed differences in pathophysiology between subtypes, namely sensorimotor-prefrontal connectivity is a key locus in OAB patients with higher urinary symptoms.

Introduction and Hypothesis: Although allusions to the importance of a good physician-patient relationship are present throughout the interstitial cystitis/bladder pain syndrome (IC/BPS) literature, qualitative analysis of patients' perspectives on the clinical encounter is lacking, particularly among women who are most commonly affected by IC/BPS. Therefore, we adopted a patient-centered experiential approach to understanding female patients' perception of clinical encounters., Methods: We re-analyzed previously collected data from a qualitative study on patient flare experiences including eight focus groups of female IC/BPS patients (n = 57, mean = 7/group). Qualitative analysis applied grounded theory to index all physician-patient interactions, then thematically coded these interactions to elucidate common experiences of clinical encounters., Results: Women with IC/BPS shared common experiences of provider disbelief and pain dismissal. Discussions with participants demonstrated the extent to which these negative encounters shape patients' health care-seeking behavior, outlook, and psychosocial well-being. Appearing in more than one guise, provider disbelief and dismissal occurred as tacit insinuations, explicit statements, silence, oversimplification, and an unwillingness to listen and discuss alternative treatment. As a result, women adopted several strategies including: rotating specialists; "testing" physicians; self-advocacy; self-management; avoiding the stigma of chronic pain; crying; and opting for alternative medicine over biomedicine., Conclusions: The prevalence of provider disbelief and pain dismissal among women with IC/BPS indicates a need to improve physician-patient communication, informed by the struggles, anxieties, and gendered inequities that female patients with chronic pain experience in their diagnostic journey. Results suggest that further investigation into the power dynamics of clinical encounters might be required., (© 2023. The International Urogynecological Association.)

We propose a practical strategy to design a series of heavy-atom-free synergistic phototherapy agents (CSQs) with both photodynamic therapy (PDT) and photothermal therapy (PTT) under NIR wavelength excitation by simply replacing the indole salt of xanthene Changsha (CS) with quinoline salt.

Objective: To examine differences in sleep disturbance, nocturia, and depression among adults with overactive bladder (OAB) by treatment type., Methods: A cross-sectional survey of adults with OAB assessed sleep disturbance, nocturia, and depression using patient-reported outcome measures, including the Patient Reported Outcomes Measurement Information System (PROMIS)-29 Profile v2.1 (Sleep Disturbance and Depression domains), Lower Urinary Tract Dysfunction Research Network Symptom Index-10, and PROMIS Sleep Disturbance Short Form 8B. Treatment groups included antimuscarinics, β-3 adrenergic agonists, and no treatment. Analysis of covariance (ANCOVA) was used to test for differences in study endpoints; Bonferroni-adjusted pairwise tests (P < .05/3) were performed to compare differences in least squares means between groups., Results: One hundred participants were included per treatment group. The overall mean (standard deviation) age across all groups was 47.8 (11.8) years. Symptom scores across all PROMIS domains in all three treatment groups were higher than the US general population. There were no statistically significant differences in outcomes across treatment groups., Conclusion: Adults with OAB reported being affected by sleep disturbance and depression, regardless of treatment. The mirabegron group trended toward the lowest symptom impact across all outcomes, however, comparisons were not significant. Future research should examine temporal associations between OAB treatment, sleep disturbance, and outcomes., Competing Interests: Declaration of Competing Interest Henry Lai received grants/contracts from NIH, Mid-West Stone Institute, Medronic. Paid consulting fees from Astellas Pharma Global Development, IronWood, MicroGenDx and Biohaven. Patent for pelvic floor EMG evaluation and probes. Participated on a Data Safety Monitoring Board for Neuraspera. David Walker is an employee of Astellas Pharma Global Development. Dina Elsouda is an employee of Astellas Pharma Global Development. Amy Lockefeer is an employee of Astellas Pharma Global Development. Kyli Gallington is an employee of Evidera, which was contracted by Astellas Pharma Global Development for the conduct of this study. Elizabeth Bacci is an employee of Evidera, which was contracted by Astellas Pharma Global Development for the conduct of this study., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Interstitial cystitis/bladder pain syndrome patients can experience overactive pelvic floor muscle activity at rest. While the frequency power spectrum of pelvic floor muscle has briefly been explored, intermuscular connectivity of the pelvic floor muscle has yet to be studied, which may provide useful insight into the neurological component, ie, neural drive to muscles, in interstitial cystitis/bladder pain syndrome., Materials and Methods: High-density surface electromyography was collected from 15 female interstitial cystitis/bladder pain syndrome patients with pelvic floor tenderness and 15 urologically healthy female controls. Intermuscular connectivity was calculated across the maximally active locations of the left and right sides of the pelvic floor muscle as identified from the root mean squared amplitude at rest and compared with Student t tests for common sensorimotor rhythms involved in motor control: alpha (8-12 Hz), beta (13-30 Hz), and gamma (31-70 Hz) frequency bands. The root mean squared amplitudes at rest were also compared across groups., Results: The resting root mean squared amplitude of the pelvic floor muscle was significantly greater in female interstitial cystitis/bladder pain syndrome patients compared to healthy female controls ( P = .0046). The gamma-band intermuscular connectivity was significantly different between rest and pelvic floor muscle contraction ( P = .0001) for healthy female controls, but not for female patients with interstitial cystitis/bladder pain syndrome ( P = .1214). Both results indicate an elevated neural drive to pelvic floor muscle at rest in female interstitial cystitis/bladder pain syndrome patients., Conclusions: Gamma-band pelvic floor muscle connectivity in female interstitial cystitis/bladder pain syndrome patients is increased at rest. The results of this study may provide insight into the impaired neural drive to pelvic floor muscle implicated with interstitial cystitis/bladder pain syndrome.

Tumor-derived exosomes and their contents promote cancer metastasis. Phosphoglycerate mutase 1 (PGAM1) is involved in various cancer-related processes. Nevertheless, the underlying mechanism of exosomal PGAM1 in prostate cancer (PCa) metastasis remains unclear. In this study, we performed in vitro and in vivo to determine the functions of exosomal PGAM1 in the angiogenesis of patients with metastatic PCa. We performed Glutathione-S-transferase pulldown, co-immunoprecipitation, western blotting and gelatin degradation assays to determine the pathway mediating the effect of exosomal PGAM1 in PCa. Our results revealed a significant increase in exosomal PGAM1 levels in the plasma of patients with metastatic PCa compared to patients with non-metastatic PCa. Furthermore, PGAM1 was a key factor initiating PCa cell metastasis by promoting invadopodia formation and could be conveyed by exosomes from PCa cells to human umbilical vein endothelial cells (HUVECs). In addition, exosomal PGAM1 could bind to γ-actin (ACTG1), which promotes podosome formation and neovascular sprouting in HUVECs. In vivo results revealed exosomal PGAM1 enhanced lung metastasis in nude mice injected with PCa cells via the tail vein. In summary, exosomal PGAM1 promotes angiogenesis and could be used as a liquid biopsy marker for PCa metastasis., (© 2023. The Author(s).)

Formononetin (FMN) is a phytoestrogen that belongs to the isoflavone family. It has antioxidant and anti-inflammatory effects, as well as, many other biological activities. Existing evidence has aroused interest in its ability to protect against osteoarthritis (OA) and promote bone remodeling. To date, research on this topic has not been thorough and many issues remain controversial. Therefore, the purpose of our study was to explore the protective effect of FMN against knee injury and clarify the possible molecular mechanisms. We found that FMN inhibited osteoclast formation induced by receptor activator of NF-κB ligand (RANKL). Inhibition of the phosphorylation and nuclear translocation of p65 in the NF-κB signaling pathway plays a role in this effect. Similarly, during the inflammatory response of primary knee cartilage cells activated by IL-1β, FMN inhibited the NF-κB signaling pathway and the phosphorylation of the ERK and JNK proteins in the MAPK signaling pathway to suppress the inflammatory response. In addition, in vivo experiments showed that both low- and high-dose FMN had a clear protective effect against knee injury in the DMM (destabilization of the medial meniscus) model, and the therapeutic effect of high-dose FMN was stronger. In conclusion, these studies provide evidence of the protective effect of FMN against knee injury., (© 2023 John Wiley & Sons Ltd.)

Objective: To describe the experiences of patients undergoing stent removal in the USDRN Study to Enhance Understanding of Stent-Associated Symptoms (STENTS), a prospective, observational cohort study of patients with short-term ureteral stent placement post-ureteroscopy., Methods: We conducted a qualitative descriptive study using in-depth interviews. Participants reflected on (1) painful or bothersome aspects of stent removal, (2) symptoms immediately after removal, and (3) symptoms in the days following removal. Interviews were audio-recorded, transcribed, and analyzed using applied thematic analysis., Results: The 38 participants interviewed were aged 13-77 years, 55% female, and 95% White. Interviews were conducted 7-30 days after stent removal. Almost all participants (n = 31) described that they experienced either pain or discomfort during stent removal, but for most (n = 25) pain was of short duration. Many participants (n = 21) described anticipatory anxiety related to the procedure, and several (n = 11) discussed discomfort arising from lack of privacy or feeling exposed. Interactions with medical providers often helped put participants at ease, but also increased discomfort for some. Following stent removal, several participants described lingering pain and/or urinary symptoms, but these largely resolved within 24 hours. A few participants described symptoms persisting for more than a day post stent removal., Conclusion: These findings on patients' experiences during and shortly after ureteral stent removal, particularly the psychological distress they experienced, identify opportunities for improvement in patient care. Clear communication from providers about what to expect with the removal procedure, and the possibility of delayed pain, may help patients adapt to discomfort., Competing Interests: Declaration of Competing Interest Carrie Dombeck: No conflict; Charles D Scales Jr: study funding NIDDK; Kevin McKenna: No conflict; Teresa Swezey: No conflict; Jonathan D. Harper: study funding NIDDK; Jodi A. Antonelli: study funding NIDDK; Alana C. Desai: study funding NIDDK; Rebecca McCune: study funding NIDDK; H. Henry Lai: study funding NIDDK; Michele Curatolo: study funding NIDDK; Hussein R. Al-Khalidi: study funding NIDDK; Peter P. Reese: study funding NIDDK; Hunter Wessells: study funding NIDDK; Ziya Kirkali: no conflicts; Amy Corneli: study funding NIDDK., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Interstitial cystitis/bladder pain syndrome (IC/BPS) can result in pelvic floor muscle (PFM) overactivity. Current clinical assessment protocols include basic electromyographic assessment of PFM activation; however, they do not provide a comprehensive assessment localized to each region of the PFM. We examined the ability of high-definition features from intravaginal high-density surface electromyography (HD-sEMG) to assess the severity of PFM overactivity in female IC/BPS patients. HD-sEMG was collected from fifteen female IC/BPS patients and fifteen urologically healthy female controls. The 2D mappings of root mean squared amplitude (RMS) at rest normalized by maximal voluntary contraction (resting RMS ratios) were segmented via k-means to identify areas of peak activity and surrounding activity. Female IC/BPS patients exhibited significantly greater resting RMS ratios for peak activity (p=0.0096), surrounding activity (p=0.0003), and average activity (p=0.0016) compared to healthy female controls. Furthermore, the area of peak activity was significantly larger for female IC/BPS patients than for healthy female controls (p=0.0063). Image segmentation of intravaginal HD-sEMG provides a more robust biomarker of PFM as compared to current methods.

Purpose: Symptom heterogeneity in interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, collectively termed urological chronic pelvic pain syndrome, has resulted in difficulty in defining appropriate clinical trial endpoints. We determine clinically important differences for 2 primary symptom measures, pelvic pain severity and urinary symptom severity, and evaluate subgroup differences., Materials and Methods: The Multidisciplinary Approach to the Study of Chronic Pelvic Pain Symptom Patterns Study enrolled individuals with urological chronic pelvic pain syndrome. We defined clinically important differences by associating changes in pelvic pain severity and urinary symptom severity over 3 to 6 months with marked improvement on a global response assessment using regression and receiver operating characteristic curves. We evaluated clinically important differences for absolute and percent change and examined differences in clinically important differences by sex-diagnosis, presence of Hunner lesions, pain type, pain widespreadness, and baseline symptom severity., Results: An absolute change of -4 was clinically important in pelvic pain severity among all patients, but clinically important difference estimates differed by pain type, presence of Hunner lesions, and baseline severity. Pelvic pain severity clinically important difference estimates for percent change were more consistent across subgroups and ranged from 30% to 57%. The absolute change urinary symptom severity clinically important difference was -3 for female participants and -2 for male participants with chronic prostatitis/chronic pelvic pain syndrome only. Patients with greater baseline severity required larger decreases in symptoms to feel improved. Estimated clinically important differences had lower accuracy among participants with low baseline symptoms., Conclusions: A reduction of 30%-50% in pelvic pain severity is a clinically meaningful endpoint for future therapeutic trials in urological chronic pelvic pain syndrome. Urinary symptom severity clinically important differences are more appropriately defined separately for male and female participants.

Purpose: Ureteral stents are commonly used after ureteroscopy and cause significant discomfort, yet qualitative perspectives on patients' stent experiences remain unknown. We describe psychological, functional, and interpersonal effects of post-ureteroscopy stents and whether additional patient-reported assessments may be needed. Materials and Methods: Using a qualitative descriptive study design, we conducted in-depth interviews with a nested cohort of participants in the STudy to Enhance uNderstanding of sTent-associated Symptoms (STENTS). Participants shared their symptoms with a post-ureteroscopy stent and described symptom bother and impact on daily activities. All interviews were audio-recorded, transcribed, and analyzed using applied thematic analysis. During analysis, participants' experiences with interference in daily activities were categorized into three groups based on their impact: minimal, moderate, and substantial. Results: All 39 participants experienced pain, although descriptions varied and differentiated between feelings of pain vs discomfort. Almost all experienced urinary symptoms. Only a few reported other physical symptoms, although several psychological aspects were identified. In the areas of sleep, mood, life enjoyment, work, exercise, activities of daily living, driving, childcare, and leisure/social activities, the stent had little impact on daily living among participants placed in the minimal group ( n  = 12) and far greater impact for participants in the substantial group ( n  = 8). For patients in the moderate group ( n  = 19), some daily activities were moderately or substantially affected, whereas other activities were minimally affected. Conclusions: Counseling to better prepare patients for the impact of stent-associated symptoms may help mitigate symptom burden. While existing instruments adequately cover most symptoms, additional assessments for other domains, particularly psychological factors, may be needed.

Objective: To explore the effects and mechanism of annexin A1 ( ANXA1 )-overexpressing human adipose-derived mesenchymal stem cells (AMSCs) in the treatment of mice with acute respiratory distress syndrome (ARDS). Methods: The experimental study method was adopted. After the adult AMSCs were identified by flow cytometry, the 3 rd passage cells were selected for the follow-up experiments. According to the random number table (the same grouping method below), the cells were divided into ANXA1-overexpressing group transfected with plasmid containing RNA sequences of ANXA1 gene and no-load control group transfected with the corresponding no-load plasmid. The other cells were divided into ANXA1-knockdown group transfected with plasmid containing small interfering RNA sequences of ANXA1 gene and no-load control group transfected with the corresponding no-load plasmid. At post transfection hour (PTH) 72, the fluorescence expression was observed under a fluorescence microscope imaging system, and the protein and mRNA expressions of ANXA1 were detected by Western blotting and real-time fluorescence quantitative reverse transcription polymerase chain reaction respectively (with the sample numbers being 3). Fifty male C57BL/6J mice aged 6-8 weeks were divided into sham injury group, ARDS alone group, normal cell group, ANXA1-overexpressing group, and ANXA1-knockdown group, with 10 mice in each group. Mice in the last 4 groups were treated with endotoxin/lipopolysaccharide to make ARDS lung injury model, and mice in sham injury group were simulated to cause false injury. Immediately after injury, mice in sham injury group and ARDS alone group were injected with normal saline through the tail vein, while mice in normal cell group, ANXA1-overexpressing group, and ANXA1-knockdown group were injected with normal AMSCs, ANXA1 -overexpressing AMSCs, and ANXA1 -knockdown AMSCs, correspondingly. At post injection hour (PIH) 24, 5 mice in each group were selected, the Evans blue staining was performed to observe the gross staining of the right lung tissue, and the absorbance value of bronchoalveolar lavage fluid (BALF) supernatant of left lung was detected by microplate reader to evaluate the pulmonary vascular permeability. Three days after injection, the remaining 5 mice in each group were taken, the right lung tissue was collected for hematoxylin-eosin staining to observe the pathological changes and immunohistochemical staining to observe the CD11b and F4/80 positive macrophages, and the levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and IL-1β in BALF supernatant of left lung were determined by enzyme-linked immunosorbent assay. Data were statistically analyzed with paired sample t test, one-way analysis of variance, and least significant difference test. Results: At PTH 72, AMSCs in both ANXA1-overexpressing group and ANXA1-knockdown group expressed higher fluorescence intensity than AMSCs in corresponding no-load control group, respectively. At PTH 72, compared with those in corresponding no-load control group, the protein and mRNA expressions of ANXA1 in ANXA1-overexpressing group were significantly increased (wth t values of 249.80 and 6.56, respectively, P <0.05), while the protein and mRNA expressions of ANXA1 in ANXA1-knockdown group were significantly decreased (wth t values of 176.50 and 18.18, respectively, P <0.05). At PIH 24, compared with those in sham injury group (with the absorbance value of BALF supernatant being 0.041±0.009), the lung tissue of mice in ARDS alone group was obviously blue-stained and the absorbance value of BALF supernatant (0.126±0.022) was significantly increased ( P <0.05). Compared with those in ARDS alone group, the degree of blue-staining in lung tissue of mice was significantly reduced in normal cell group or ANXA1-overexpressing group, and the absorbance values of BALF supernatant (0.095±0.020 and 0.069±0.015) were significantly decreased ( P <0.05), but the degree of blue-staining in lung tissue and the absorbance value of BALF supernatant (0.109±0.016, P >0.05) of mice in ANXA1-knockdown group had no significant change. Compared with that in normal cell group, the absorbance value of BALF supernatant of mice in ANXA1-overexpressing group was significantly decreased ( P <0.05). Three days after injection, the lung tissue structure of mice in ARDS alone group was significantly damaged compared with that in sham injury group. Compared with those in ARDS alone group, hemorrhage, infiltration of inflammatory cells, alveolar collapse, and interstitial widening in the lung tissue of mice were significantly alleviated in normal cell group and ANXA1-overexpressing group, while no significant improvement of above-mentioned lung tissue manifestation was observed in ANXA1-knockdown group. Three days after injection, the numbers of CD11b and F4/80 positive macrophages in the lung tissue of mice in ARDS alone group were significantly increased compared with those in sham injury group. Compared with those in ARDS alone group, the numbers of CD11b and F4/80 positive macrophages in lung tissue of mice in normal cell group, ANXA1-overexpressing group, and ANXA1-knockdown group reduced, with the most significant reduction in ANXA1-overexpressing group. Three days after injection, compared with those in sham injury group, the levels of TNF-α, IL-6, and IL-1β in BALF supernatant of mice in ARDS alone group were significantly increased ( P <0.05). Compared with those in ARDS alone group, the levels of TNF-α, IL-6, and IL-1β in BALF supernatant of mice in normal cell group and ANXA1-overexpressing group, as well as the level of IL-1β in BALF supernatant of mice in ANXA1-knockdown group were significantly decreased ( P <0.05). Compared with that in normal cell group, the level of TNF-α in BALF supernatant of mice was significantly decreased in ANXA1-overexpressing group ( P <0.05) but significantly increased in ANXA1-knockdown group ( P <0.05). Conclusions: Overexpression of ANXA1 can optimize the efficacy of AMSCs in treating ARDS and enhance the effects of these cells in inhibiting inflammatory response and improving pulmonary vascular permeability, thereby alleviating lung injury of mice with ARDS.

Purpose: The STudy to Enhance uNderstanding of sTent-associated Symptoms sought to identify risk factors for pain and urinary symptoms, as well as how these symptoms interfere with daily activities after ureteroscopy for stone treatment., Materials and Methods: This prospective observational cohort study enrolled patients aged ≥12 years undergoing ureteroscopy with ureteral stent for stone treatment at 4 clinical centers. Participants reported symptoms at baseline; on postoperative days 1, 3, 5; at stent removal; and day 30 post-stent removal. Outcomes of pain intensity, pain interference, urinary symptoms, and bother were captured with multiple instruments. Multivariable analyses using mixed-effects linear regression models were identified characteristics associated with increased stent-associated symptoms., Results: A total of 424 participants were enrolled. Mean age was 49 years (SD 17); 47% were female. Participants experienced a marked increase in stent-associated symptoms on postoperative day 1. While pain intensity decreased ∼50% from postoperative day 1 to postoperative day 5, interference due to pain remained persistently elevated. In multivariable analysis, older age was associated with lower pain intensity ( P = .004). Having chronic pain conditions ( P < .001), prior severe stent pain ( P = .021), and depressive symptoms at baseline ( P < .001) were each associated with higher pain intensity. Neither sex, stone location, ureteral access sheath use, nor stent characteristics were drivers of stent-associated symptoms., Conclusions: In this multicenter cohort, interference persisted even as pain intensity decreased. Patient factors (eg, age, depression) rather than surgical factors were associated with symptom intensity. These findings provide a foundation for patient-centered care and highlight potential targets for efforts to mitigate the burden of stent-associated symptoms.

Background: Although jaw asymmetry is commonly seen in skeletal Class III patients, its correlation with occlusal function and masticatory muscle activity has not been fully elucidated., Objectives: The purpose of this study was to investigate the occlusal function and masticatory muscle activity in skeletal Class III patients with various patterns of mandibular asymmetry., Methods: Forty-two patients and 10 normal participants were examined. The patients were categorised into three groups. Groups 1 and 2 exhibited menton and ramus deviation to the same side. Menton deviation was larger than ramus deviation in Group 1, whereas Group 2 showed the inverse relation. Group 3 patients showed menton and ramus deviation in opposite directions. Occlusal contact area (OCA), relative bite force (RBF), and temporalis anterior (TA) and masseter muscle (MM) activity at maximum clenching were measured using T-Scan Novus system and Bio-EMG-III. Statistical analysis was performed using the t-test, one-way analysis of variance with Bonferroni correction and Spearman correlation (α = .05)., Results: Compared with normal participants, the patients had smaller OCA and greater asymmetry in the distribution of masticatory muscle activity. Greater ramus deviation was associated with smaller OCA in Group 1 but with larger OCA in Group 3. In Group 1, greater menton deviation was related to stronger TA activity on the non-deviation side. In Group 2, greater ramus deviation was related to stronger MM activity on the deviation side., Conclusion: Deviation of the menton and ramus was individually related to OCA and masticatory muscle activity, and this relationship varied according to the pattern of mandibular asymmetry., (© 2023 John Wiley & Sons Ltd.)

Background: To better understand the sensation of bladder "pressure" and "discomfort", and how they are similar or distinct from the "pain" and "urgency" symptoms in IC/BPS and OAB., Methods: IC/BPS and OAB patients rated their bladder pain, pressure, discomfort, and urinary urgency on separate 0-10 numeric rating scales (NRS). Their NRS ratings were compared between IC/BPS and OAB, and Pearson correlations were performed., Results: Among IC/BPS patients (n = 27), their mean numeric ratings of pain, pressure, discomfort, and urinary urgency were almost identical (6.6 ± 2.1, 6.0 ± 2.5, 6.5 ± 2.2, and 6.0 ± 2.8 respectively). The three-way correlations between pain, pressure, or discomfort were very strong (all > 0.77). Among OAB patients (n = 51), their mean numeric ratings of pain, pressure, and discomfort (2.0 ± 2.6, 3.4 ± 2.9, 3.4 ± 2.9) were significantly lower than urgency (6.1 ± 2.6, p < 0.001). The correlations between urgency and pain, and between urgency and pressure were weak in OAB (0.21 and 0.26). The correlation between urgency and discomfort was moderate in OAB (0.45). The most bothersome symptom of IC/BPS was bladder/pubic pain, while the most bothersome symptom of OAB was urinary urgency and daytime frequency., Conclusions: IC/BPS patients interpreted bladder pain, pressure, or discomfort as the similar concepts and rated their intensity similarly. It is unclear whether pressure or discomfort provide additional information beyond pain in IC/BPS. Discomfort may also be confused with urgency in OAB. We should re-examine the descriptors pressure or discomfort in the IC/BPS case definition., (© 2023. The Author(s).)

Neuronal circuits regulating appetite are dominated by arcuate nucleus neurons, which include appetite-promoting and -suppressing neurons that release the orexigenic neuropeptide agouti-related protein (AgRP) and anorexigenic neuropeptide pro-opiomelanocortin, respectively, to compete for melanocortin receptors to modulate feeding behavior. In this study, we expressed novel agrp promoters, including different lengths of the 5' flanking regions of the agrp gene (4749 bp) in the zebrafish genome. We used the agrp promoter to derive the enhanced green fluorescent protein (EGFP)-nitroreductase (NTR) fusion protein, allowing expression of the green fluorescence signal in the AgRP neurons. Then, we treated the transgenic zebrafish AgRP4.7 NTR (Tg [ agrp-EGFP-NTR ]) with metronidazole to ablate the AgRP neurons in the larvae stage and observed a decline in their appetite and growth. The expression of most orexigenic and growth hormone/insulin-like growth factor axis genes decreased, whereas that of several anorexigenic genes increased. Our findings demonstrate that AgRP is a critical regulator of neuronal signaling for zebrafish appetite and energy intake control. Thus, AgRP4.7 NTR can be used as a drug-screening platform for therapeutic targets to treat human appetite disorders, including obesity. Furthermore, the unique agrp promoter we identified can be a powerful tool for research on AgRP neurons, especially AgRP neuron-mediated pathways in the hypothalamus, and appetite.

Purpose: Most studies on interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome use typical or average levels of pelvic pain or urological symptom intensity as their outcome, as both are associated with reduced quality of life. Symptom exacerbations or "flares" have also been found to be associated with reduced quality of life, but no studies, to our knowledge, have investigated whether these associations are independent of typical pelvic pain levels and thus might be useful additional outcome measures (or stated differently, whether reducing flare frequency even without reducing mean pain intensity may be important to patients)., Materials and Methods: We used screening visit and weekly run-in period data from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Symptom Patterns Study to investigate associations between flare frequency and multiple measures of illness impact and health care seeking activity, independent of typical nonflare and overall pelvic pain levels., Results: Among the 613 eligible participants, greater flare frequency was associated with worse condition-specific illness impact (standardized β coefficients=0.11-0.68, P trends < .0001) and health care seeking activity (odds ratios=1.52-3.94, P trends .0039 to < .0001) in analyses adjusted for typical nonflare and overall pelvic pain levels. Experiencing ≥1/d was also independently associated with worse general illness impact (standardized β coefficients=0.11-0.25)., Conclusions: Our findings suggest that flare frequency and possibly other flare characteristics may be worth considering as additional outcome measures in urological chronic pelvic pain syndrome research to support the development of new preventive and therapeutic flare strategies.

Objective: To investigate whether the mitochondrial DNA (mtDNA) content of a single biopsy at trophoblast correlates with the developmental potential and reproductive outcomes of blastocyst., Methods: A retrospective analysis applied the dataset of 1,675 embryos with preimplantation genetic testing for aneuploidy (PGT-A) from 1,305 individuals, and 1,383 embryos involved cryotransfers of single euploid embryo between January 2015 and December 2019. The studied cohort was divided for algorithm establishment on the NGS platform (n=40), correlation of biological features (n=1,635), and correlation of reproductive outcomes (n=1,340). Of the algorithm derived from the NGS platform, the reliability and repeatability were validated via qPCR assay and inter-run controls, respectively. Of the correlation across biological features, stratification analyses were applied to evaluate the effect from a single contributor. Eventually, the correlation between the mtDNA ratios and reproductive outcomes was adjusted according to the significant effector(s)., Results: The mtDNA ratios showed statistically different between embryos with different days of blastocyst formation ([Day 5]: 1.06 vs. [Day 6]: 0.66, p=0.021), and between embryos with different expansion stages ([Expansion 5]: 1.05 vs. [Expansion 6]: 0.49, p=0.012). None or weakly correlated with the maternal age, morphology, ploidy, and gender. Analyzed by the different days of blastocyst formation with fixed expansion score as 5 in the euploid single embryo transfers (eSET), the day 6 eSET showed significantly lower reduced mtDNA ratio (n=139) in failure groups of fetal heartbeat (p=0.004), ongoing pregnancy (p=0.007), and live birth (p=0.01); however, no correlation between mtDNA ratios and pregnancy outcomes was observed in the day 5 eSET (n=1,201)., Conclusions: The study first demonstrated that mtDNA ratio was dependent on the days of blastocyst formation while expansion stage was fixed. Lower mtDNA ratios were observed in the day 6 eSET with adverse outcomes. The present stratification analyses reveal that the timeline of embryo is an important covariate to the mtDNA content., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chuang, Chen, Kuan, Lai, Hsieh, Lee, Liang, Chang, Chen and Chen.)

Purpose: We characterize patients with urinary urgency with vs without urgency urinary incontinence who presented to clinics actively seeking treatment for their symptoms., Materials and Methods: Participants who enrolled in the Symptoms of Lower Urinary Tract Dysfunction Research Network were categorized into urinary urgency with vs without urgency urinary incontinence. Participants were followed for 1 year; their urinary symptoms, urological pain, psychosocial factors, bowel function, sleep disturbance, physical activity levels, physical function, and quality of life were compared. Mixed effects linear regression models were used to examine the relationships between urgency urinary incontinence and these factors., Results: Among 683 participants with urinary urgency at baseline, two-thirds (n=453) also had urgency urinary incontinence; one-third (n=230) had urinary urgency-only without urgency urinary incontinence. No differences were detected in urological pain between urinary urgency-only and urgency urinary incontinence. Those with urgency urinary incontinence had more severe urgency and frequency symptoms, higher depression, anxiety, perceived stress scores, more severe bowel dysfunction and sleep disturbance, lower physical activity levels, lower physical function, and worse quality of life than those with urinary urgency-only. Among those with urinary urgency-only at baseline, 40% continued to have urinary urgency-only, 15% progressed to urgency urinary incontinence, and 45% had no urgency at 12 months. Fifty-eight percent with urgency urinary incontinence at baseline continued to report urgency urinary incontinence at 12 months, while 15% improved to urinary urgency-only, and 27% had no urgency., Conclusions: Patients with urgency urinary incontinence have severe storage symptoms, more psychosocial symptoms, poorer physical functioning, and worse quality of life. Our data suggested urgency urinary incontinence may be a more severe manifestation of urinary urgency, rather than urinary urgency and urgency urinary incontinence being distinct entities.

Introduction: Caffeine has long been vilified as a cause for urinary urgency incontinence (UUI) along with other potential bladder irritants such as carbonation, alcohol, and acidic juices. The objective of this study was to assess the fluid intake behavior of people with urgency, UUI, and those with lower urinary tract symptoms (LUTS) without UUI or urgency to assess if they avoided certain potential bladder irritants or had different fluid intake. We hypothesized that patients with UUI would avoid caffeine as a self-management method more so than these other two groups., Methods: Treatment-seeking men and women with LUTS in the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) Observational Cohort study completed a baseline 3-day voiding and intake diary. "Complete" diaries had 3 days of data and no missing intake or voided volumes. Beverages with any caffeine, alcohol, carbonation, or acidic juice were identified and the total volume was recorded as well as the type of beverage containing caffeine to calculate the daily caffeine dose., Results: Four hundred and ninety-one participants (277 men and 214 women) with a median age of 63 had complete diaries. Urinary urgency was more prevalent in women than men (79% vs. 55%, p < 0.0001) as was UUI (84% vs. 47%, p < 0.0001). Total fluid intake over 3 days was lower among the urgency group versus the nonurgency group (median [interquartile range] 5.2 [4.0-6.8] L vs. 5.7 [4.3-7.0] L, p = 0.028) and the UUI group compared to the urgency without incontinence group were less likely to consume alcohol (26% vs. 37%, p = 0.04). After adjusting for sex, BMI, age, and total intake volume, UUI participants had 54% lower odds of consuming any caffeine (odds ratio = 0.46, 95% confidence interval = 0.22-0.96, p = 0.04) than those without incontinence, but among those that did consume caffeine, no difference in the volume of caffeinated beverages or milligrams of caffeine consumed was detected between those with UUI and those with urgency without incontinence. No difference in carbonation or acidic juice intake was detected between groups., Conclusions: Individuals with urgency consume a lower volume of fluid than those without urgency. UUI participants more often abstain from caffeine, but among those that consume caffeine, the dose is similar to those without UUI. One explanation for these results is that only a subset of individuals with urgency or UUI are caffeine sensitive., (© 2022 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.)