Ketamine is a popular choice for young drug abusers. Ketamine abuse causes lower urinary tract symptoms, with the underlying pathophysiology poorly understood. Disruption of urothelial barrier ...function has been hypothesized to be a major mechanism for ketamine cystitis, yet the direct evidence of impaired urothelial barrier function is still lacking. To address this question, 8-wk-old female C57BL/6J mice were injected intraperitoneally with 30 mg·kg(-1)·day(-1) ketamine for 12 wk to induce ketamine cystitis. A spontaneous voiding spot assay showed that ketamine-treated mice had increased primary voiding spot numbers and smaller primary voiding spot sizes than control mice (P < 0.05), indicating a contracted bladder and bladder overactivity. Consistently, significantly increased voiding frequency was observed in ketamine-treated mice on cystometrograms. These functional experiments indicate that ketamine induces voiding dysfunction in mice. Surprisingly, urothelial permeability in ketamine-treated mice was not changed when measured using an Ussing chamber system with isotopic urea and water. Mouse urothelial structure was also not altered, and intact umbrella cell structure was observed by both transmission and scanning electron microscopy. Furthermore, immunostaining and confocal microscopy confirmed the presence of a well-defined distribution of zonula occuldens-1 in tight junctions and uroplakin in umbrella cells. In conclusion, these data indicate that ketamine injection induces voiding dysfunction in mice but does not necessarily disrupt mouse bladder barrier function. Disruption of urothelial barrier function may not be the major mechanism in ketamine cystitis.
Although genome-wide association studies (GWAS) for prostate cancer (PrCa) have identified more than 100 risk regions, most of the risk genes at these regions remain largely unknown. Here we ...integrate the largest PrCa GWAS (N = 142,392) with gene expression measured in 45 tissues (N = 4458), including normal and tumor prostate, to perform a multi-tissue transcriptome-wide association study (TWAS) for PrCa. We identify 217 genes at 84 independent 1 Mb regions associated with PrCa risk, 9 of which are regions with no genome-wide significant SNP within 2 Mb. 23 genes are significant in TWAS only for alternative splicing models in prostate tumor thus supporting the hypothesis of splicing driving risk for continued oncogenesis. Finally, we use a Bayesian probabilistic approach to estimate credible sets of genes containing the causal gene at a pre-defined level; this reduced the list of 217 associations to 109 genes in the 90% credible set. Overall, our findings highlight the power of integrating expression with PrCa GWAS to identify novel risk loci and prioritize putative causal genes at known risk loci.
The present study was aimed at the identification of proteins that are differentially expressed in the urine of patients with prostate cancer (PCa), those with benign prostatic hyperplasia (BPH) and ...age‐matched healthy male control subjects. Using a combination of 2DE and MS/MS, significantly lower expression of urinary saposin B and two different fragments of inter‐alpha‐trypsin inhibitor light chain (ITIL) was demonstrated in the PCa patients compared to the controls. However, only one of the ITIL fragments was significantly different between the PCa and BPH patients. When image analysis was performed on urinary proteins that were transferred onto NC membranes and detected using a lectin that binds to O‐glycans, a truncated fragment of inter‐alpha‐trypsin inhibitor heavy chain 4 was the sole protein found to be significantly enhanced in the PCa patients compared to the controls. Together, these urinary peptide fragments might be useful complementary biomarkers to indicate PCa as well as to distinguish it from BPH, although further epidemiological evidence on the specificity and sensitivity of the protein candidates is required.
Introduction
The common assumption that urinary incontinence occurs in osteoarthritis (OA) due to poor mobility is supported by limited evidence. The influence of gender in such associations is also ...yet to be elucidated.
Objective
This study, therefore, identified any potential associations between knee OA symptoms and urinary incontinence and further explore sex differences in the associations.
Design
Cross‐sectional study.
Setting
University Hospital.
Participants
This was a cross‐sectional study from a longitudinal research study comprising 1221 community‐dwelling older persons (57% women), mean age (SD) 68.95 (7.49) years.
Main Outcome Measure(s)
Presence of urinary incontinence: mixed, stress and urge symptoms. Physical performance and C‐reactive protein levels were also assessed.
Results
Two hundred and seventy‐seven (22.83%) individuals reported the presence of urinary incontinence: mixed (41.5%), stress (30%), and urge (28.5%) symptoms. In an unadjusted analysis, stratified by gender, the association between knee pain and urinary incontinence was only present in women with mixed symptoms. After further adjustment of demographics differences and body mass index, the association between knee pain with any urinary incontinence and mixed symptoms remained significant with the odds ratios (95% confidence interval): 1.48 (1.02–2.15) and 1.73 (1.06–2.83), respectively. This relationship was attenuated after further adjustment for waist circumference and impaired lower limb mobility.
Conclusion
Our study refutes previous assumptions that urinary incontinence in individuals with OA is attributed to impaired mobility alone, but introduces the role of abdominal obesity in this relationship, particularly in women. Future studies should assess the temporal relationship between body fat distribution and OA with urinary incontinence.
Objective
To investigate non‐urological patients with multiple comorbidities for factors contributing towards differences in testosterone concentration in multiethnic Malaysian men.
Design
An ...observational study.
Patients
Sexually active men, ≥40 years, with no known urological problems, were recruited at the phlebotomy clinic at our centre.
Measurements
A brief history along with latest fasting lipid profile and plasma glucose levels were obtained. An Aging Male Symptoms questionnaire was administered; waist circumference (WC) and serum testosterone concentration were measured.
Statstical Analysis
Analysis of testosterone concentration between Malay, Indian and Chinese men was performed. Statistical tests such as analysis of variance, χ2 test, univariate and multivariable regression were performed. Any p < .05 was noted as statistically significant.
Results
Among the 604 participants analysed, mean testosterone concentration was significantly lower in Malays (15.1 ± 5.9 nmol/L) compared to the Chinese (17.0 ± 5.9 nmol/L) and Indian (16.1 ± 6.5 nmol/L) participants. The mean WC was also found to be higher among the Malays (96.1 ± 10.9 cm) compared to Chinese (92.6 ± 9.6 cm) and Indians (95.6 ± 9.9 cm). Testosterone concentration tended to be lower with higher age, but this was not statistically significant (p > .05). In the multivariable analysis only Malay ethnicity, WC ≥ 90 cm and low high‐density lipoprotein (HDL) were associated with lower testosterone concentration.
Conclusion
In this study, Malaysian men of Malay origin had lower testosterone concentration compared with Indian and Chinese men. WC and low HDL were also associated with lower testosterone concentrations.
Objectives
To document the management of advanced prostate cancer including diagnosis, prognosis, treatment, and care, in real‐world practice in Asia using the United in Fight against prOstate cancer ...(UFO) registry.
Patients and Methods
We established a multi‐national, longitudinal, observational registry of patients with prostate cancer presenting to participating tertiary care hospitals in eight Asian countries. A total of 3636 eligible patients with existing or newly diagnosed high‐risk localised prostate cancer (HRL), non‐metastatic biochemically recurrent prostate cancer (M0), or metastatic prostate cancer (M1), were consecutively enrolled and are being followed‐up for 5 years. Patient history, demographic and disease characteristics, treatment and treatment decisions, were collected at first prostate cancer diagnosis and at enrolment. Patient‐reported quality of life was prospectively assessed using the European Quality of Life‐five Dimensions, five Levels (EQ‐5D‐5L) and Functional Assessment of Cancer Therapy for Prostate Cancer questionnaires. In the present study, we report the first interim analysis of 2063 patients enrolled from study start (15 September 2015) until 18 May 2017.
Results
Of the 2063 enrolled patients, 357 (17%), 378 (19%), and 1328 (64%) had HRL, M0 or M1 prostate cancer, respectively. The mean age at first diagnosis was similar in each group, 56% of all patients had extracapsular extension of their tumour, 28% had regional lymph node metastasis, and 53% had distant metastases. At enrolment, 62% of patients had at least one co‐morbidity (mainly cardiovascular disease or diabetes), 91.8% of M1 patients had an Eastern Cooperative Oncology Group performance score of <2 and the mean EQ‐5D‐5L visual analogue score was 74.6–79.6 across cohorts. Treatment of M1 patients was primarily with combined androgen blockade (58%) or androgen‐deprivation therapy (either orchidectomy or luteinising hormone‐releasing hormone analogues) (32%). Decisions to start therapy were mainly driven by treatment guidelines and disease progression. Decision to discontinue therapy was most often due to disease progression (hormonal drug therapy) or completion of therapy (chemotherapy).
Conclusion
In the UFO registry of advanced prostate cancer in Asia, regional differences exist in prostate cancer treatment patterns that will be explored more deeply during the follow‐up period; prospective follow‐up is ongoing. The UFO registry will provide valuable descriptive data on current disease characteristics and treatment landscape amongst patients with prostate cancer in Asia.
Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS
) is associated with age at prostate ...cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS
(PHS
, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS
is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p < 10
). Comparing the 80
/20
PHS
percentiles, hazard ratios for prostate cancer, aggressive cancer, and prostate-cancer-specific death are 5.32, 5.88, and 5.68, respectively. Within European, Asian, and African ancestries, hazard ratios for prostate cancer are: 5.54, 4.49, and 2.54, respectively. PHS
risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.
Diagnosis of prostate cancer (PCa) is currently much reliant on the invasive and time‐consuming transrectal ultrasound‐guided biopsy of the prostate gland, particularly in light of the inefficient ...use of prostate‐specific antigen as its biomarker. In the present study, we have profiled the sera of patients with PCa and benign prostatic hyperplasia (BPH) using the gel‐ and lectin‐based proteomics methods and demonstrated the significant differential expression of apolipoprotein AII, complement C3 beta chain fragment, inter‐alpha‐trypsin inhibitor heavy chain 4 fragment, transthyretin, alpha‐1‐antitrypsin, and high molecular weight kininogen (light chain) between the two groups of patients’ samples. Our data are suggestive of the potential use of the serum proteins as complementary biomarkers to effectively discriminate PCa from BPH, although this requires further extensive validation on clinically representative populations.
Genome-wide association studies (GWAS) have advanced our understanding of susceptibility to B-cell precursor acute lymphoblastic leukemia (BCP-ALL); however, much of the heritable risk remains ...unidentified. Here, we perform a GWAS and conduct a meta-analysis with two existing GWAS, totaling 2442 cases and 14,609 controls. We identify risk loci for BCP-ALL at 8q24.21 (rs28665337, P = 3.86 × 10
, odds ratio (OR) = 1.34) and for ETV6-RUNX1 fusion-positive BCP-ALL at 2q22.3 (rs17481869, P = 3.20 × 10
, OR = 2.14). Our findings provide further insights into genetic susceptibility to ALL and its biology.
While being in a committed relationship is associated with a better prostate cancer prognosis, little is known about how marital status relates to its incidence. Social support provided by ...marriage/relationship could promote a healthy lifestyle and an increased healthcare seeking behavior. We investigated the association between marital status and prostate cancer risk using data from the PRACTICAL Consortium. Pooled analyses were conducted combining 12 case–control studies based on histologically-confirmed incident prostate cancers and controls with information on marital status prior to diagnosis/interview. Marital status was categorized as married/partner, separated/divorced, single, or widowed. Tumours with Gleason scores ≥ 8 defined high-grade cancers, and low-grade otherwise. NCI-SEER’s summary stages (local, regional, distant) indicated the extent of the cancer. Logistic regression was used to derive odds ratios (ORs) and 95% confidence intervals (CI) for the association between marital status and prostate cancer risk, adjusting for potential confounders. Overall, 14,760 cases and 12,019 controls contributed to analyses. Compared to men who were married/with a partner, widowed men had an OR of 1.19 (95% CI 1.03–1.35) of prostate cancer, with little difference between low- and high-grade tumours. Risk estimates among widowers were 1.14 (95% CI 0.97–1.34) for local, 1.53 (95% CI 1.22–1.92) for regional, and 1.56 (95% CI 1.05–2.32) for distant stage tumours. Single men had elevated risks of high-grade cancers. Our findings highlight elevated risks of incident prostate cancer among widowers, more often characterized by tumours that had spread beyond the prostate at the time of diagnosis. Social support interventions and closer medical follow-up in this sub-population are warranted.
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