Genomes of the Banyan Tree and Pollinator Wasp Provide Insights into Fig-Wasp Coevolution.

Banyan trees are distinguished by their extraordinary aerial roots. The Ficus genus includes species that have evolved a species-specific mutualism system with wasp pollinators. We sequenced genomes of the Chinese banyan tree, F. microcarpa, and a species lacking aerial roots, F. hispida, and one wasp genome coevolving with F. microcarpa, Eupristina verticillata. Comparative analysis of the two Ficus genomes revealed dynamic karyotype variation associated with adaptive evolution. Copy number expansion of auxin-related genes from duplications and elevated auxin production are associated with aerial root development in F. microcarpa. A male-specific AGAMOUS paralog, FhAG2, was identified as a candidate gene for sex determination in F. hispida. Population genomic analyses of Ficus species revealed genomic signatures of morphological and physiological coadaptation with their pollinators involving terpenoid- and benzenoid-derived compounds. These three genomes offer insights into and genomic resources for investigating the geneses of aerial roots, monoecy and dioecy, and codiversification in a symbiotic system.

Genome-wide association study reveals ethnicity-specific SNPs associated with ankylosing spondylitis in the Taiwanese population.

BACKGROUND: Ankylosing spondylitis (AS) is an autoimmune disease affecting mainly spine and sacroiliac joints and adjacent soft tissues. Genome-wide association studies (GWASs) are used to evaluate genetic associations and to predict genetic risk factors that determine the biological basis of disease susceptibility. We aimed to explore the race-specific SNP susceptibility of AS in Taiwanese individuals and to investigate the association between HLA-B27 and AS susceptibility SNPs in Taiwan. METHODS: Genotyping data were collected from a medical center participating in the Taiwan Precision Medicine Initiative (TPMI) in the northern district of Taiwan. We designed a case-control study to identify AS susceptibility SNPs through GWAS. We searched the genome browser to find the corresponding susceptibility genes and used the GTEx database to confirm the regulation of gene expression. A polygenic risk score approach was also applied to evaluate the genetic variants in the prediction of developing AS. RESULTS: The results showed that the SNPs located on the sixth chromosome were related to higher susceptibility in the AS group. There was no overlap between our results and the susceptibility SNPs found in other races. The 12 tag SNPs located in the MHC region that were found through the linkage disequilibrium method had higher gene expression. Furthermore, Taiwanese people with HLA-B27 positivity had a higher proportion of minor alleles. This might be the reason that the AS prevalence is higher in Taiwan than in other countries. We developed AS polygenic risk score models with six different methods in which those with the top 10% polygenic risk had a fivefold increased risk of developing AS compared to the remaining group with low risk. CONCLUSION: A total of 147 SNPs in the Taiwanese population were found to be statistically significantly associated with AS on the sixth pair of chromosomes and did not overlap with previously published sites in the GWAS Catalog. Whether those genes mapped by AS-associated SNPs are involved in AS and what the pathogenic mechanism of the mapped genes is remain to be further studied.

Genome-wide analyses identify novel risk loci for cluster headache in Han Chinese residing in Taiwan.

BACKGROUND: Cluster headache is a highly debilitating neurological disorder with considerable inter-ethnic differences. Genome-wide association studies (GWAS) recently identified replicable genomic loci for cluster headache in Europeans, but the genetic underpinnings for cluster headache in Asians remain unclear. The objective of this study is to investigate the genetic architecture and susceptibility loci of cluster headache in Han Chinese resided in Taiwan. METHODS: We conducted a two-stage genome-wide association study in a Taiwanese cohort enrolled from 2007 through 2022 to identify the genetic variants associated with cluster headache. Diagnosis of cluster headache was retrospectively ascertained with the criteria of International Classification of Headache Disorders, third edition. Control subjects were enrolled from the Taiwan Biobank. Genotyping was conducted with the Axiom Genome-Wide Array TWB chip, followed by whole genome imputation. A polygenic risk score was developed to differentiate patients from controls. Downstream analyses including gene-set and tissue enrichment, linkage disequilibrium score regression, and pathway analyses were performed. RESULTS: We enrolled 734 patients with cluster headache and 9,846 population-based controls. We identified three replicable loci, with the lead SNPs being rs1556780 in CAPN2 (odds ratio = 1.59, 95% CI 1.42‒1.78, p = 7.61 × 10-16), rs10188640 in MERTK (odds ratio = 1.52, 95% CI 1.33‒1.73, p = 8.58 × 10-13), and rs13028839 in STAB2 (odds ratio = 0.63, 95% CI 0.52‒0.78, p = 2.81 × 10-8), with the latter two replicating the findings in European populations. Several previously reported genes also showed significant associations with cluster headache in our samples. Polygenic risk score differentiated patients from controls with an area under the receiver operating characteristic curve of 0.77. Downstream analyses implicated circadian regulation and immunological processes in the pathogenesis of cluster headache. CONCLUSIONS: This study revealed the genetic architecture and novel susceptible loci of cluster headache in Han Chinese residing in Taiwan. Our findings support the common genetic contributions of cluster headache across ethnicities and provide novel mechanistic insights into the pathogenesis of cluster headache.

Elucidating Mechanisms of Bladder Repair after Hyaluronan Instillation in Ketamine-Induced Ulcerative Cystitis in Animal Model.

Ketamine-induced ulcerative cystitis (KIC) initially damaged the bladder mucosa and induced contracted bladder thereafter. Hyaluronan (hyaluronic acid; HA) instillation to the bladder has been used to treat KIC. The present study investigated bladder injury by urothelial defect and HA degeneration and bladder repair by urothelium proliferation and differentiation. This work was based on the hypothesis that HA treatment altered the bladder urothelial layer and the expression of hyaluronan-metabolizing enzymes and/or HA receptors in KIC. Cystometrogram study and tracing analysis of voiding behavior revealed that the ketamine-treated rats exhibited significant bladder hyperactivity with an increase in micturition frequency and a decrease in bladder capacity. The expression of inflammatory and fibrosis markers was also increased in the ketamine-treated group. Moreover, ketamine administration decreased the expression of urothelial barrier-associated protein, altered HA production, and induced abnormal urothelial differentiation, which might attribute to urothelial lining defects. However, HA instillation ameliorated bladder hyperactivity, lessened bladder mucosa damage, and decreased interstitial fibrosis. HA instillation also improved the level of HA receptors (CD44, Toll-like receptor-4, and receptor for HA-mediated motility) and HA synthases 1 to 3 and decreased the expression of hyaluronidases in the urothelial layer of bladder, resulting in enhanced mucosal regeneration. These findings suggested that HA could modulate inflammatory responses, enhance mucosal regeneration, and improve urothelial lining defects in KIC.

Breaking down Leukemia Walls: Heteronemin, a Sesterterpene Derivative, Induces Apoptosis in Leukemia Molt4 Cells through Oxidative Stress, Mitochondrial Dysfunction and Induction of Talin Expression.

Heteronemin, the most abundant secondary metabolite in the sponge Hippospongia sp., exhibited potent cytotoxic activity against several cancer cell lines. It increased the percentage of apoptotic cells and reactive oxygen species (ROS) in Molt4 cells. The use of ROS scavenger, N-acetyl cysteine (NAC), suppressed both the production of ROS from mitochondria and cell apoptosis that were induced by heteronemin treatment. Heteronemin upregulated talin and phosphorylated talin expression in Molt4 cells but it only upregulated the expression of phosphorylated talin in HEK293 cells. However, pretreatment with NAC reversed these effects. Talin siRNA reversed the activation of pro-apoptotic cleaved caspases 3 and 9. On the other hand, the downstream proteins including FAK and NF-κB (p65) were not affected. In addition, we confirmed that heteronemin directly modulated phosphorylated talin expression through ROS generation resulting in cell apoptosis, but it did not affect talin/FAK complex. Furthermore, heteronemin interfered with actin microfilament and caused morphology changes. Taken together, these findings suggest that the cytotoxic effect of heteronemin is associated with oxidative stress and induction of phosphorylated talin expression. Our results suggest that heteronemin represents an interesting candidate which can be further developed as a drug lead against leukemia.

Heteronemin, a Marine Sesterterpenoid-Type Metabolite, Induces Apoptosis in Prostate LNcap Cells via Oxidative and ER Stress Combined with the Inhibition of Topoisomerase II and Hsp90.

Heteronemin, a marine sesterterpenoid-type natural product, possesses diverse bioactivities, especially antitumor effect. Accumulating evidence shows that heteronemin may act as a potent anticancer agent in clinical therapy. To fully understand the antitumor mechanism of heteronemin, we further explored the precise molecular targets in prostate cancer cells. Initially, heteronemin exhibited potent cytotoxic effect against LNcap and PC3 prostate cancer cells with IC50 1.4 and 2.7 μM after 24 h, respectively. In the xenograft animal model, the tumor size was significantly suppressed to about 51.9% in the heteronemin-treated group in comparison with the control group with no significant difference in the mice body weights. In addition, the results of a cell-free system assay indicated that heteronemin could act as topoisomerase II (topo II) catalytic inhibitor through the elimination of essential enzymatic activity of topoisomerase IIα expression. We found that the use of heteronemin-triggered apoptosis by 20.1⁻68.3%, caused disruption of mitochondrial membrane potential (MMP) by 66.9⁻99.1% and promoted calcium release by 1.8-, 2.0-, and 2.1-fold compared with the control group in a dose-dependent manner, as demonstrated by annexin-V/PI, rhodamine 123 and Fluo-3 staining assays, respectively. Moreover, our findings indicated that the pretreatment of LNcap cells with an inhibitor of protein tyrosine phosphatase (PTPi) diminished growth inhibition, oxidative and Endoplasmic Reticulum (ER) stress, as well as activation of Chop/Hsp70 induced by heteronemin, suggesting PTP activation plays a crucial rule in the cytotoxic activity of heteronemin. Using molecular docking analysis, heteronemin exhibited more binding affinity to the N-terminal ATP-binding pocket of Hsp90 protein than 17-AAG, a standard Hsp90 inhibitor. Finally, heteronemin promoted autophagy and apoptosis through the inhibition of Hsp 90 and topo II as well as PTP activation in prostate cancer cells. Taken together, these multiple targets present heteronemin as an interesting candidate for its future development as an antiprostatic agent.

Translocation of NF-κB and expression of cyclooxygenase-2 are enhanced by ketamine-induced ulcerative cystitis in rat bladder.

The number of ketamine abusers has increased significantly recently. Ketamine abusers exhibit urinary frequency, urgency, and at times urinary incontinence. Our aim was to investigate the role of transcription factor NF-κB and cyclooxygenase (COX)-2 in ketamine-induced cystitis. Sprague-Dawley rats were distributed into three groups, which received saline or treatment with ketamine or ketamine combined with a Cox-2 inhibitor (parecoxib). In addition, the toxic effect of ketamine and its metabolites were examined by primary urothelial cell culture. The ketamine-treated group displayed bladder hyperactivity and decreased bladder capacity. Treatment with ketamine + COX-2 inhibitor prevented these bladder dysfunctions. These bladder dysfunctions were accompanied by increases in the expression of NF-κB and COX-2 at the protein and mRNA levels. Ketamine treatment also enhanced bladder interstitial fibrosis, whereas ketamine + Cox-2 inhibitor decreased the intensity of fibrosis. Treatment of primary urothelial cells in vitro with ketamine or urine obtained from ketamine-treated rats stimulated the expression of NF-κB p65 and COX-2. Ketamine also initiated NF-κB translocation from cell cytoplasm to nucleus. Treatment with NF-κB inhibitor suppressed Cox-2 mRNA expression. Promoter-deletion analysis revealed that NF-κB was a necessary transcription factor for COX-2 gene (Ptgs2) activation. These results demonstrate that the regulation of COX-2 via the NF-κB pathway is involved in the inflammatory signaling of ketamine-induced cystitis in rat urinary bladder.

Ketamine-induced ulcerative cystitis and bladder apoptosis involve oxidative stress mediated by mitochondria and the endoplasmic reticulum.

Ketamine abusers develop severe lower urinary tract symptoms. The major aims of the present study were to elucidate ketamine-induced ulcerative cystitis and bladder apoptosis in association with oxidative stress mediated by mitochondria and the endoplasmic reticulum (ER). Sprague-Dawley rats were distributed into three different groups, which received normal saline or ketamine for a period of 14 or 28 days, respectively. Double-labeled immunofluorescence experiments were performed to investigate tight junction proteins for urothelial barrier functions. A TUNEL assay was performed to evaluate the distribution of apoptotic cells. Western blot analysis was carried out to examine the expressions of urothelial tight junction proteins, ER stress markers, and apoptosis-associated proteins. Antioxidant enzymes, including SOD and catalase, were investigated by real-time PCR and immunofluorescence experiments. Ketamine-treated rats were found to display bladder hyperactivity. This bladder dysfunction was accompanied by disruptions of epithelial cadherin- and tight junction-associated proteins as well as increases in the expressions of apoptosis-associated proteins, which displayed features of mitochondria-dependent apoptotic signals and ER stress markers. Meanwhile, expressions of mitochondria respiratory subunit enzymes were significantly increased in ketamine-treated bladders. Conversely, mRNA expressions of the antioxidant enzymes Mn-SOD (SOD2), Cu/Zn-SOD (SOD1), and catalase were decreased after 28 days of ketamine treatment. These results demonstrate that ketamine enhanced the generation of oxidative stress mediated by mitochondria- and ER-dependent pathways and consequently contributed to bladder apoptosis and urothelial lining defects. Such oxidative stress-enhanced bladder cell apoptosis and urothelial barrier defects are potential factors that may play a crucial role in bladder overactivity and ulceration.

Trans-ancestry polygenic models for the prediction of LDL blood levels: an analysis of the United Kingdom Biobank and Taiwan Biobank.

Polygenic risk score (PRS) predictions often show bias toward the population of available genome-wide association studies (GWASs), which is typically of European ancestry. This study aimed to assess the performance differences of ancestry-specific PRS and test the implementation of multi-ancestry PRS to enhance the generalizability of low-density lipoprotein (LDL) cholesterol predictions in the East Asian (EAS) population. In this study, we computed ancestry-specific and multi-ancestry PRSs for LDL using data obtained from the Global Lipid Genetics Consortium, while accounting for population-specific linkage disequilibrium patterns using the PRS-CSx method in the United Kingdom Biobank dataset (UKB, n = 423,596) and Taiwan Biobank dataset (TWB, n = 68,978). Population-specific PRSs were able to predict LDL levels better within the target population, whereas multi-ancestry PRSs were more generalizable. In the TWB dataset, covariate-adjusted R 2 values were 9.3% for ancestry-specific PRS, 6.7% for multi-ancestry PRS, and 4.5% for European-specific PRS. Similar trends (8.6%, 7.8%, and 6.2%) were observed in the smaller EAS population of the UKB (n = 1,480). Consistent with R 2 values, PRS stratification in EAS regions (TWB) effectively captured a heterogenous variability in LDL blood cholesterol levels across PRS strata. The mean difference in LDL levels between the lowest and highest EAS-specific PRS (EAS_PRS) deciles was 0.82, compared to 0.59 for European-specific PRS (EUR_PRS) and 0.76 for multi-ancestry PRS. Notably, the mean LDL values in the top decile of multi-ancestry PRS were comparable to those of EAS_PRS (3.543 vs. 3.541, p = 0.86). Our analysis of the PRS prediction model for LDL cholesterol further supports the issue of PRS generalizability across populations. Our targeted analysis of the EAS population revealed that integrating non-European genotyping data with a powerful European-based GWAS can enhance the generalizability of LDL PRS.

Green tea catechins decrease oxidative stress in surgical menopause-induced overactive bladder in a rat model.

UNLABELLED: What's known on the subject? and What does the study add? Ovary hormone deficiency and the age-related changes in post-menopausal women are subjected to a number of urological dysfunctions, including overactive bladder syndrome. Green tea is a popular healthy drink worldwide and its extract catechin has strong anti-inflammatory and antioxidant properties. EGCG, the major type of catechin, is an antioxidant polyphenol flavonoid isolated from green tea. EGCG supplement could prevent ovariectomy-induced bladder dysfunction in a dose-related manner through its anti-oxidant, anti-fibrosis and anti-apoptosis effects. OBJECTIVE: To evaluate whether green tea extract, epigallocatechin gallate (EGCG), could prevent ovariectomy-induced overactive bladder (OAB) and to investigate its antioxidant, anti-apoptotic and anti-fibrosis effects. MATERIALS AND METHODS: In all, 48 female Sprague-Dawley rats were divided into four groups. After bilateral ovariectomy, the first group served as the ovariectomy control, the second group received EGCG 1 µM/kg daily i.p. injection after ovariectomy surgery, and the third group received EGCG 10 µM/kg daily i.p. injection. The fourth group was taken as the sham without ovariectomy surgery. The rats were killed after 6 months after ovariectomy surgery. Cystometrograms were performed for the measure of bladder overactivity. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling (TUNEL) assay was used to evaluate apoptotic cells. Western immunoblots were performed to determine the expressions of inflammatory markers, apoptosis-associated proteins and oxidative stress markers. RESULTS: Long-term ovariectomy significantly increased non-voiding contractions and decreased bladder compliance. Treatment with EGCG significantly increased bladder compliance and diminished non-voiding contractions. Ovariectomy significantly increased apoptotic cells and enhanced interstitial fibrosis in bladders. The expression of caspase-3 significantly increased, while that of Bcl-2 notably decreased after ovariectomy. Inflammatory and fibrosis markers, TGF-ß, fibronectin and type I collagen expressions were significantly increased after 6 months of ovariectomy surgery. Treatment with EGCG significantly decreased TGF-ß and type I collagen expressions. Oxidative stress markers, nitrotyrosine and protein carbonylation levels were significantly increased in the ovariectomy group. EGCG could attenuate this oxidative damage in dose-dependent fashion. CONCLUSIONS: Ovariectomy increased oxidative damage, enhanced voiding frequency and decreased bladder compliance. EGCG could restore ovariectomy-induced bladder dysfunction in a dose-dependent fashion through antioxidant, anti-fibrosis and anti-apoptosis effects.

Headache as the sole symptom of nasopharyngeal carcinoma and its clinical implications.

BACKGROUND: This study aimed to investigate the clinical features of NPC presenting with headache as the primary or sole symptom. METHODS: The authors retrospectively identified 14 cases of NPC with headache as the initial presentation between 2003 and 2008. Headache characteristics, tumor staging, and treatment outcomes were assessed. RESULTS: Most patients had either T4 (n = 12) or T3 (n = 1) tumor. The average duration of headaches prior to NPC diagnosis was 7.9 months. The location of the headaches was most commonly described as temporal or parietal with various pain patterns. Six patients (43%) experienced unilateral headache during attacks while the remaining patients reported bilateral or diffuse pain. Of the 14 patients, 10 (71%) experienced significant improvement in head pain during or after the treatment; most of them reported relief shortly after chemoradiation was initiated. The 5-year overall survival of these patients was similar to that of other NPC patients. CONCLUSION: Headache can be the only symptom of NPC. A timely diagnosis, albeit challenging to physicians, provides good outcomes in terms of both pain relief and tumor control.

Development and Validation of a Deep Learning Model Using Convolutional Neural Networks to Identify Scaphoid Fractures in Radiographs.

Importance: Scaphoid fractures are the most common carpal fracture, but as many as 20% are not visible (ie, occult) in the initial injury radiograph; untreated scaphoid fractures can lead to degenerative wrist arthritis and debilitating pain, detrimentally affecting productivity and quality of life. Occult scaphoid fractures are among the primary causes of scaphoid nonunions, secondary to delayed diagnosis. Objective: To develop and validate a deep convolutional neural network (DCNN) that can reliably detect both apparent and occult scaphoid fractures from radiographic images. Design, Setting, and Participants: This diagnostic study used a radiographic data set compiled for all patients presenting to Chang Gung Memorial Hospital (Taipei, Taiwan) and Michigan Medicine (Ann Arbor) with possible scaphoid fractures between January 2001 and December 2019. This group was randomly split into training, validation, and test data sets. The images were passed through a detection model to crop around the scaphoid and were then used to train a DCNN model based on the EfficientNetB3 architecture to classify apparent and occult scaphoid fractures. Data analysis was conducted from January to October 2020. Exposures: A DCNN trained to discriminate radiographs with normal and fractured scaphoids. Main Outcomes and Measures: Area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity. Fracture localization was assessed using gradient-weighted class activation mapping. Results: Of the 11 838 included radiographs (4917 [41.5%] with scaphoid fracture; 6921 [58.5%] without scaphoid fracture), 8356 (70.6%) were used for training, 1177 (9.9%) for validation, and 2305 (19.5%) for testing. In the testing test, the first DCNN achieved an overall sensitivity and specificity of 87.1% (95% CI, 84.8%-89.2%) and 92.1% (95% CI, 90.6%-93.5%), respectively, with an AUROC of 0.955 in distinguishing scaphoid fractures from scaphoids without fracture. Gradient-weighted class activation mapping closely corresponded to visible fracture sites. The second DCNN achieved an overall sensitivity of 79.0% (95% CI, 70.6%-71.6%) and specificity of 71.6% (95% CI, 69.0%-74.1%) with an AUROC of 0.810 when examining negative cases from the first model. Two-stage examination identified 20 of 22 cases (90.9%) of occult fracture. Conclusions and Relevance: In this study, DCNN models were trained to identify scaphoid fractures. This suggests that such models may be able to assist with radiographic detection of occult scaphoid fractures that are not visible to human observers and to reliably detect fractures of other small bones.

A Multimodal Imaging-Based Deep Learning Model for Detecting Treatment-Requiring Retinal Vascular Diseases: Model Development and Validation Study.

BACKGROUND: Retinal vascular diseases, including diabetic macular edema (DME), neovascular age-related macular degeneration (nAMD), myopic choroidal neovascularization (mCNV), and branch and central retinal vein occlusion (BRVO/CRVO), are considered vision-threatening eye diseases. However, accurate diagnosis depends on multimodal imaging and the expertise of retinal ophthalmologists. OBJECTIVE: The aim of this study was to develop a deep learning model to detect treatment-requiring retinal vascular diseases using multimodal imaging. METHODS: This retrospective study enrolled participants with multimodal ophthalmic imaging data from 3 hospitals in Taiwan from 2013 to 2019. Eye-related images were used, including those obtained through retinal fundus photography, optical coherence tomography (OCT), and fluorescein angiography with or without indocyanine green angiography (FA/ICGA). A deep learning model was constructed for detecting DME, nAMD, mCNV, BRVO, and CRVO and identifying treatment-requiring diseases. Model performance was evaluated and is presented as the area under the curve (AUC) for each receiver operating characteristic curve. RESULTS: A total of 2992 eyes of 2185 patients were studied, with 239, 1209, 1008, 211, 189, and 136 eyes in the control, DME, nAMD, mCNV, BRVO, and CRVO groups, respectively. Among them, 1898 eyes required treatment. The eyes were divided into training, validation, and testing groups in a 5:1:1 ratio. In total, 5117 retinal fundus photos, 9316 OCT images, and 20,922 FA/ICGA images were used. The AUCs for detecting mCNV, DME, nAMD, BRVO, and CRVO were 0.996, 0.995, 0.990, 0.959, and 0.988, respectively. The AUC for detecting treatment-requiring diseases was 0.969. From the heat maps, we observed that the model could identify retinal vascular diseases. CONCLUSIONS: Our study developed a deep learning model to detect retinal diseases using multimodal ophthalmic imaging. Furthermore, the model demonstrated good performance in detecting treatment-requiring retinal diseases.

The Anti-Proliferative Activity of Secondary Metabolite from the Marine Streptomyces sp. against Prostate Cancer Cells.

Many active substances from marine organisms are produced by symbiotic microorganisms such as bacteria, fungi, and algae. Secondary metabolites from marine actinomycetes exhibited several biological activities and provided interesting drug leads. This study reported the isolation of Lu01-M, a secondary metabolite from the marine actinomycetes Streptomyces sp., with potent anti-proliferative activity against prostate cancers. Lu01-M blocked cell proliferation with IC50 values of 1.03 ± 0.31, 2.12 ± 0.38, 1.27 ± 0.25 µg/mL in human prostate cancer PC3, DU145, and LNCaP cells, respectively. Lu01-M induced cytotoxic activity through multiple mechanisms including cell apoptosis, necroptosis, autophagy, ER stress, and inhibiting colony formation and cell migration. Lu01-M induced cell cycle arrest at the G2/M phase and DNA damage. However, the activity of autophagy induced survival response in cancer cells. Our findings suggested that Lu01-M holds the potential to be developed as an anti-cancer agent against prostate cancers.

Epigallocatechin-3-gallate alleviates bladder overactivity in a rat model with metabolic syndrome and ovarian hormone deficiency through mitochondria apoptosis pathways.

Metabolic syndrome (MetS) and ovarian hormone deficiency could affect bladder storage dysfunction. Epigallocatechin-3-gallate (EGCG), a polyphenolic compound in green tea, has been shown to protect against ovarian hormone deficiency induced overactive bladder (OAB). The present study investigated oxidative stress induced by MetS and bilateral ovariectomy (OVX), and elucidated the mechanism underlying the protective effect of EGCG (10 umol/kg/day) on bladder overactivity. Rats were fed with high fat high sugar (HFHS) diet to induce MetS and received ovariectomy surgery to deprive ovarian hormone. By dieting with HFHS for 6 months, rats developed MetS and OAB. MetS + OVX deteriorated bladder storage dysfunction more profound than MetS alone. MetS and MetS + OVX rats showed over-expression of inflammatory and fibrosis markers (1.7~3.8-fold of control). EGCG pretreatment alleviated storage dysfunction, and protected the bladders from MetS and OVX - induced interstitial fibrosis changes. Moreover, OVX exacerbated MetS related bladder apoptosis (2.3~4.5-fold of control; 1.8~2.6-fold of Mets group), enhances oxidative stress markers (3.6~4.3-fold of control; 1.8~2.2-fold of Mets group) and mitochondrial enzyme complexes subunits (1.8~3.7-fold of control; 1.5~3.4-fold of Mets group). EGCG pretreatment alleviated bladder apoptosis, attenuated oxidative stress, and reduced the mitochondrial and endoplasmic reticulum apoptotic signals. In conclusions, HFHS feeding and ovarian hormone deficiency enhances the generation of oxidative stress mediated through mitochondrial pathway. EGCG reduced the generation of oxidative stress and lessened bladder overactivity.

Noncontrast computed tomography factors that predict the renal stone outcome after shock wave lithotripsy.

OBJECTIVES: Extracorporeal shock wave lithotripsy (ESWL) is a popular treatment for nephrolithiasis. We took advantage of noncontrast abdominal computed tomography (NCCT) to search the possible prognostic factors including abdominal fat distribution influencing stone-free rate. METHODS: From August 2008 to August 2010, 145 patients who had renal calculus and had undergone ESWL were retrospectively reviewed. All of them received NCCT assessment before ESWL and were followed up after 1 month for stone clearance. These patients were divided into two groups: one was the stone-free group and the other was the residual-stone group. Affecting parameters included stone size, location, stone surface area, Hounsfield unit density (HU density), skin-to-stone distance (SSD), and abdominal fat area as analyzed between these two groups. RESULTS: Of 145 patients, 70 were stone-free and 75 had residual stone after ESWL treatment and 1-month follow-up. From univariate analysis, stone size, HU density, SSD, and stone surface area were significant predicting factors for ESWL success. On multivariate analysis, the important factors influencing ESWL outcomes were HU density and stone surface area (odds ratio 1.002 vs. 77.18, respectively; P<.05). Abdominal fat accumulation and distribution had no significant difference between these two groups. CONCLUSION: This study revealed that stone size, HU density, SSD, and stone surface area were associated with stone-free rate after ESWL treatment. Therefore, these factors could be used to assess the feasibility of ESWL before deciding the treatment strategy. Abdominal fat distribution had no significant impact on ESWL outcome for renal stones.

Testicular sparing surgery for bilateral epidermoid cysts of the testes: a case report.

We report the case of a 12-year-old boy with bilateral epidermoid cysts of the testes diagnosed preoperatively from ultrasonography, magnetic resonance imaging, and negative tumor markers. The cysts were treated using bilateral testicular sparing surgery through a scrotal approach after intraoperative frozen section. We also discuss the diagnosis and management of epidermoid cyst of the testis and briefly review the literature.

Clinical and urographic presentation of transitional cell carcinoma of the ureter in a blackfoot disease endemic area in southern Taiwan.

We reviewed the clinical, radiographic, and pathologic findings of ureteral transitional cell carcinoma (TCC) in a blackfoot disease (BFD) endemic area in southern Taiwan to increase understanding of tumor behavior in this area, which has a high incidence of urothelium carcinoma. From August 1995 to February 2002, 28 histologically proven ureteral TCCs from this area were eligible for study. There was an unusual female predominance (male:female ratio, 1:1.333). The urographic filling defects in the 28 ureteral TCCs were classified into four categories. An ovoid filling defect was significantly associated with non-invasive tumors (p = 0.003) and a trend toward low tumor grades (p = 0.073). The risk of ureteral TCC in this BFD endemic area of southern Taiwan remained high between August 1995 and February 2002. Urographic surveillance provides a simple, clear, inexpensive method to study the extent, location, and morphology of the ureteral mass. Detailed assessment of the image could be useful for preoperative planning and predicting prognosis. Large-scale, randomized, prospective clinical trials are needed to validate our results.

Correlation between filling defect patterns on urography and pathologic staging of ureteral transitional cell carcinomas.

Although a filling defect within the ureter is the most common finding with ureteral transitional cell carcinomas (TCCs), little is known about the correlation between filling defect patterns and pathologic findings. This study was conducted to address this. Between January 1995 and January 2003, 126 pathologically confirmed TCCs of the ureter were included in our study. We classified urographic filling defects into four patterns: ovoid, polypoid, infiltrating, and plaque-like. The correlation between different filling defect patterns and pathologic findings was assessed using Pearson's Chi-squared and logistic regression methods. There were 28 (22%) ovoid filling defects, 42 (33%) polypoid filling defects, 37 (29%) infiltrating filling defects, and 19 (15%) plaque-like filling defects. Infiltrating and plaque-like filling defects were significantly associated with more advanced disease compared to ovoid and polypoid filling defects (odds ratio, 6.75; 95% confidence interval, 3.04-14.98; p < 0.0001). Our results suggest that filling defect presentations may signify different invasive behavior among TCCs. The distribution of ovoid, polypoid, infiltrating, and plaque-like filling defect patterns is significantly different between superficial and advanced ureteral TCCs. We suggest that classifying the filling defect patterns of ureteral TCCs may provide important preoperative information for planning treatment and predicting outcome.

Use of narrow band imaging in evaluation of possible nasopharyngeal carcinoma.

BACKGROUND: This study was designed to evaluate the narrow band imaging (NBI) system for its ability to differentiate between malignant neoplasm and benign neoplasm by real-time image during nasopharyngoscopy, the quality of the visualization, and the limitation of the NBI in nasopharyngeal lesions. METHODS: Between June 2009 and May 2010, 63 patients who had a suspected nasopharyngeal tumor via nasopharyngoscopy at Taipei Veterans General Hospital, Taiwan, were included in this study. All of the patients received nasopharyngoscopy with conventional view and NBI view and nasopharyngeal biopsy. The patients were divided into two groups depending on the pathological results: nasopharyngeal carcinoma (NPC) and lymphoid hyperplasia/chronic inflammation (LH). RESULTS: Forty-one patients were in the NPC group and 22 patients were in the LH group. The pattern of the NBI view showed regular cobblestone in the LH group, except for one patient. The pattern of the NBI view showed an irregular engorged vascular pattern and/or microvascular proliferative pattern in 32 of 41 NPC patients (78.0%). The sensitivity, specificity, positive predictive value, and negative predictive value of NBI in nasopharynx (NP) were 78.0, 95.5, 97.0, and 70.0%, respectively, in NP neoplasm. CONCLUSION: NBI could be helpful in differentiating benign and malignant neoplasm in the NP region. Using NBI in NP regions had some limitations, including bleeding and mucus coating.