Gender differences in the associations between knee pain and urinary incontinence in older adults: Cross-sectional analysis from the Malaysian Elders Longitudinal Research Study (MELoR).

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.

Ethnic differences in serum testosterone concentration among Malay, Chinese and Indian men: A cross-sectional study.

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.

Inhibition of Janus Kinase 1 synergizes docetaxel sensitivity in prostate cancer cells.

Prostate cancer (PCa) is the second most common malignancy and is the fifth leading cause of cancer mortality among men globally. Docetaxel-based therapy remains the first-line treatment for metastatic castration-resistant prostate cancer. However, dose-limiting toxicity including neutropenia, myelosuppression and neurotoxicity is the major reason for docetaxel dose reductions and fewer cycles administered, despite a recent study showing a clear survival benefit with increased total number of docetaxel cycles in PCa patients. Although previous studies have attempted to improve the efficacy and reduce docetaxel toxicity through drug combination, no drug has yet demonstrated improved overall survival in clinical trial, highlighting the challenges of improving the activity of docetaxel monotherapy in PCa. Herein, we identified 15 lethality hits for which inhibition could enhance docetaxel sensitivity in PCa cells via a high-throughput kinome-wide loss-of-function screen. Further drug-gene interactions analyses identified Janus kinase 1 (JAK1) as a viable druggable target with existing experimental inhibitors and FDA-approved drugs. We demonstrated that depletion of endogenous JAK1 enhanced docetaxel-induced apoptosis in PCa cells. Furthermore, inhibition of JAK1/2 by baricitinib and ruxolitinib synergizes docetaxel sensitivity in both androgen receptor (AR)-negative DU145 and PC3 cells, but not in the AR-positive LNCaP cells. In contrast, no synergistic effects were observed in cells treated with JAK2-specific inhibitor, fedratinib, suggesting that the synergistic effects are mainly mediated through JAK1 inhibition. In conclusion, the combination therapy with JAK1 inhibitors and docetaxel could be a useful therapeutic strategy in the treatment of prostate cancers.

Marital status and prostate cancer incidence: a pooled analysis of 12 case-control studies from the PRACTICAL consortium.

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.

Phosphoinositide-dependent Kinase-1 (PDPK1) regulates serum/glucocorticoid-regulated Kinase 3 (SGK3) for prostate cancer cell survival.

Prostate cancer (PCa) is the most common malignancy and is the second leading cause of cancer among men globally. Using a kinome-wide lentiviral small-hairpin RNA (shRNA) library screen, we identified phosphoinositide-dependent kinase-1 (PDPK1) as a potential mediator of cell survival in PCa cells. We showed that knock-down of endogenous human PDPK1 induced significant tumour-specific cell death in PCa cells (DU145 and PC3) but not in the normal prostate epithelial cells (RWPE-1). Further analyses revealed that PDPK1 mediates cancer cell survival predominantly via activation of serum/glucocorticoid-regulated kinase 3 (SGK3). Knock-down of endogenous PDPK1 in DU145 and PC3 cells significantly reduced SGK3 phosphorylation while ectopic expression of a constitutively active SGK3 completely abrogated the apoptosis induced by PDPK1. In contrast, no such effect was observed in SGK1 and AKT phosphorylation following PDPK1 knock-down. Importantly, PDPK1 inhibitors (GSK2334470 and BX-795) significantly reduced tumour-specific cell growth and synergized docetaxel sensitivity in PCa cells. In summary, our results demonstrated that PDPK1 mediates PCa cells' survival through SGK3 signalling and suggest that inactivation of this PDPK1-SGK3 axis may potentially serve as a novel therapeutic intervention for future treatment of PCa.

United in Fight against prOstate cancer (UFO) registry: first results from a large, multi-centre, prospective, longitudinal cohort study of advanced prostate cancer in Asia.

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.

Management of advanced prostate cancer in a middle-income country: real-world consideration of the Advanced Prostate Cancer Consensus Conference 2017.

OBJECTIVE: To examine the results of the Malaysian Advanced Prostate Cancer Consensus Conference (MyAPCCC) 2018, held for assessing the generalizability of consensus reached at the Advanced Prostate Cancer Consensus Conference (APCCC 2017) to Malaysia, a middle-income country. METHODS: Six key sections were chosen: (1) high-risk localized and locally advanced prostate cancer, (2) oligometastatic prostate cancer, (3) castration-naïve prostate cancer, (4) castrate resistant prostate cancer, (5) use of osteoclast-targeted therapy and (6) global access to prostate cancer drugs. There were 101 consensus questions, consisting of 91 questions from APCCC 2017 and 10 new questions from MyAPCCC 2018, selected and modified by the steering committee; of which, 23 questions were assessed in both ideal world and real-world settings. A panel of 22 experts, comprising of 11 urologists and 11 oncologists, voted on 101 predefined questions anonymously. Final voting results were compared with the APCCC 2017 outcomes. RESULTS: Most voting results from the MyAPCCC 2018 were consistent with the APCCC 2017 outcomes. No consensus was achieved for controversial topics with little level I evidence, such as management of oligometastatic disease. No consensus was reached on using high-cost drugs in castration-naïve or castration-resistant metastatic prostate cancer in real-world settings. All panellists recommended using generic drugs when available. CONCLUSIONS: The MyAPCCC 2018 voting results reflect the management of advanced prostate cancer in a middle-income country in a real-world setting. These results may serve as a guide for local clinical practices and highlight the financial challenges in modern healthcare.

Intact urothelial barrier function in a mouse model of ketamine-induced voiding dysfunction.

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.

Urine of patients with early prostate cancer contains lower levels of light chain fragments of inter-alpha-trypsin inhibitor and saposin B but increased expression of an inter-alpha-trypsin inhibitor heavy chain 4 fragment.

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.

Impact of applied progressive deep muscle relaxation training on the health related quality of life among prostate cancer patients--a quasi experimental trial.

PURPOSE: To determine the impact of applied progressive muscle relaxation training on health related quality of life among prostate cancer patients. METHOD: A quasi-experimental study was conducted at the University Malaya Medical Centre (UMMC) and Universiti Kebangsaan Malaysia Medical Centre (UKMMC) over six months. Patients from UMMC received the intervention and patients from UKMMC as a comparison group. The general health related quality of life was measured using Short Form-36 (SF-36). RESULTS: A total of 77 patients from the intervention group and 78 patients from the comparison group participated in the study. At the end of the study, only 90.9% in intervention group and 87.2% in comparison group completed the study. There were significant differences between intervention and comparison groups for mental component summary (MCS) (p=0.032) and overall health related quality of life (p=0.042) scores. However, there was no significant difference between groups for physical component summary (PCS) (p=0.965). CONCLUSION: The improvement in MCS and overall QOL showed the potential of APMRT in the management of prostate cancer patients. Future studies should be carried out over a longer duration to provide stronger evidence for the introduction of relaxation therapy among prostate cancer patients as a coping strategy to improve their QOL.

Muslim prayer movements as an alternative therapy in the treatment of erectile dysfunction: a preliminary study.

[Purpose] Our objective was to assess the effect of salat and mimicking salat movements and postures on subjects with erectile dysfunction. [Methods] Ten volunteers were recruited in this study. Subjects who were Muslims (Group I) were asked to perform their daily salat and a new intervention of an additional 12 movement cycles of salat for three sessions a week. Non-Muslim subjects (Group II) were taught to mimic salat movements, and were asked to perform a total of 12 movement cycles without reading the recitation for three sessions a week. An International Index for Erectile Function 5 (IIEF-5) questionnaire was given to the subjects before and after the intervention of performing salat or mimicking salat movements and postures. A nocturnal electrobioimpedance volume assessment (NEVA) device was used to measure the nocturnal penile tumescence (NPT) parameters over two consecutive nights. A nonparametric test was conducted to find the significant NPT parameters. [Results] The results showed that all measured parameters improved significantly, with the largest change observed in the maximum percent volumetric change over the baseline (from 138 to 222%). [Conclusion] This preliminary study suggests that the alternative approach of salat and mimicking salat movements and postures, may have beneficial effects for ED patients.

Differential Protein Expression Patterns of HOXA13 and HOXB13 Are Associated with Bladder Cancer Progression.

Bladder cancer is a common urological cancer and has the highest recurrence rate of any cancer. The aim of our study was to profile and characterize the protein expression of homeobox A13 (HOXA13) and homeobox B13 (HOXB13) genes in Malaysian bladder cancer patients. The protein expression of HOXA13 and HOXB13 in formalin-fixed paraffin-embedded (FFPE) bladder cancer tissues was determined by immunohistochemistry (IHC) analysis. The association between HOXA13/HOXB13 protein expression and demographic/clinicopathological characteristics of the bladder cancer patients was determined by chi-square analysis. Approximately 63.6% of the bladder cancer tissues harbored high HOXA13 expression. High HOXA13 expression was significantly associated with non-muscle invasive bladder cancer, lower tumor grade, higher number of lymph node metastases, and recurrence risk. In contrast, low HOXB13 expression (including those with negative expression) was observed in 71.6% of the bladder cancer tissues analyzed. Low HOXB13 expression was significantly associated with muscle-invasive bladder cancer, higher tumor stage, tumor grade, and metastatic risk. Both HOXA13 and HOXB13 protein expression were found to be associated with bladder tumorigenesis. The putative oncogenic and tumor suppressive roles of HOXA13 and HOXB13, respectively, suggest their potential utility as biomarkers in bladder cancer.

Analysis of PPI networks of transcriptomic expression identifies hub genes associated with Newcastle disease virus persistent infection in bladder cancer.

Bladder cancer cells can acquire persistent infection of oncolytic Newcastle disease virus (NDV) but the molecular mechanism(s) remain unelucidated. This poses a major barrier to the effective clinical translation of oncolytic NDV virotherapy of cancers. To improve our understanding of the molecular mechanism(s) associated with the development of NDV persistent infection in bladder cancer, we used mRNA expression profiles of persistently infected bladder cancer cells to construct PPI networks. Based on paths and modules in the PPI network, the bridges were found mainly in the upregulated mRNA-pathways of p53 signalling, ECM-receptor interaction, and TGF-beta signalling and downregulated mRNA-pathways of antigen processing and presentation, protein processing in endoplasmic reticulum, completement and coagulation cascades in persistent TCCSUPPi cells. In persistent EJ28Pi cells, connections were identified mainly through upregulated mRNA-pathways of renal carcinoma, viral carcinogenesis, Ras signalling and cell cycle and the downregulated mRNA-pathways of Wnt signalling, HTLV-I infection and pathways in cancers. These connections were mainly dependent on RPL8-HSPA1A/HSPA4 in TCCSUPPi cells and EP300, PTPN11, RAC1-TP53, SP1, CCND1 and XPO1 in EJ28Pi cells. Oncomine validation showed that the top hub genes identified in the networks that include RPL8, THBS1, F2 from TCCSUPPi and TP53 and RAC1 from EJ28Pi are involved in the development and progression of bladder cancer. Protein-drug interaction networks identified several putative drug targets that could be used to disrupt the linkages between the modules and prevent bladder cancer cells from acquiring NDV persistent infection. This novel PPI network analysis of differentially expressed mRNAs of NDV persistently infected bladder cancer cell lines provide an insight into the molecular mechanisms of NDV persistency of infection in bladder cancers and the future screening of drugs that can be used together with NDV to enhance its oncolytic efficacy.

Identification of potential complementary serum biomarkers to differentiate prostate cancer from benign prostatic hyperplasia using gel- and lectin-based proteomics analyses.

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.

A Study on the Immunohistochemical Expressions of Leptin and Leptin Receptor in Clear Cell Renal Cell Carcinoma.

BACKGROUND: The mechanisms that link obesity and cancer development are not well-defined. Investigation of leptin and leptin receptor expressions may help define some of the mechanisms. These proteins are known for associating with the immune response, angiogenesis and, signalling pathways such as JAK2/STAT3, PI3K, and AKT pathways. Tissue proteins can be easily detected with immunohistochemistry (IHC), a technique widely used both in diagnostic and research laboratories. The identification of altered levels of leptin and leptin receptor proteins in tumour tissues may lead to targeted treatment for cancer. OBJECTIVE: The objective of this study was to use IHC to compare leptin and leptin receptor expressions in clear cell renal cell carcinomas (ccRCC) in non-obese and obese patients to determine the association between these proteins with the clinicopathological features and prognosis of ccRCC. Patients and Methods. The study involved 60 patients who underwent nephrectomy of which 34 were obese, as assessed using body mass index (BMI). Nephrectomy samples provided tissues of ccRCC and adjacent non-cancerous kidney. The intensity and localization of leptin and leptin receptor protein expressions were evaluated using IHC and correlated with clinicopathological features and clinical outcomes. Aperio ImageScope morphometry and digital pathology were applied to assess the IHC results. The chi-square test was used to determine if there was any significant association between the proteins and the clinicopathological features. The Kaplan-Meier test was used to determine the overall survival, disease-free survival, and recurrence-free survival. A value of p < 0.05 was considered significant. RESULTS: There was neither significant difference in the overall cellular and nuclear expressions of leptin and leptin receptor between non-cancerous kidney and ccRCC tissues nor in non-obese and obese individuals with ccRCC. CONCLUSION: In this present study, it was revealed that leptin and leptin receptor were not associated with tumour characteristics and progression of ccRCC patients. Interestingly, nuclear expression of leptin was significantly associated with overall survival. However, the significance of these proteins as biomarkers in other RCC histotypes is still unclear.

Predictive factors of prostate cancer diagnosis with PSA 4.0-10.0 ng/ml in a multi-ethnic Asian population, Malaysia.

OBJECTIVES: To identify the associated factors determining prostate cancer detection using transrectal ultrasound (TRUS)-guided prostate biopsy, within a multi-ethnic Malaysian population with prostate specific antigen (PSA) between 4.0 and 10.0 ng/ml. METHODS: Study subjects included men with initial PSA between 4.0 and 10.0 ng/ml that have undergone 12-core TRUS-guided prostate biopsy between 2009 and 2016. The prostate cancer detection rate was calculated, while potential factors associated with detection were investigated via univariable and multivariable analysis. RESULTS: A total of 617 men from a multi-ethnic background encompassing Chinese (63.5%), Malay (23.1%) and Indian (13.3%) were studied. The overall cancer detection rate was 14.3% (88/617), which included cancers detected at biopsy 1 (first biopsy), biopsy 2 (second biopsy with previous negative biopsy) and biopsy ≥ 3 (third or more biopsies with prior negative biopsies). Indian men displayed higher detection rate (23.2%) and increased risk of prostate cancer development (OR 1.85, 95% CI 1.03-3.32, p < 0.05), compared to their Malay (9.8%) and Chinese (14.0%) counterparts. Multivariable analysis revealed that ethnicity and PSA density (PSAD) are independent factors associated with overall prostate cancer detection rate. A unit increase of PSAD reflected an increase in PSA after controlling for prostate volume. CONCLUSION: Prostate cancer detection in Malaysia is comparatively lower. Our study suggests that ethnicity and PSA density should be considered when recommending first or repeat TRUS-guided prostate biopsy for prostate cancer detection in a multi-ethnic Malaysian population.

Evaluation of CERS2 Gene as a Potential Biomarker for Bladder Cancer.

The ceramide synthase 2 (CERS2) gene has been linked to tumour recurrence and invasion in many different types of cancers including bladder cancer. In this study, the expression levels of CERS2 in bladder cancer cell lines were analysed using qRT-PCR and the protein expression in clinical bladder cancer histopathological specimens were examined via immunohistochemistry. The potential utility of CERS2 as a predictive biomarker of response to oncolytic virotherapy was assessed by correlating the CERS2 mRNA expression to IC50 values of cells treated with the Newcastle disease virus (NDV), AF2240 strain. This study demonstrates that CERS2 is differentially expressed in different types of bladder cancer cell lines and that the siRNA-mediated downregulation of the expression of CERS2 reduces the migratory potential of UMUC1 bladder cancer cells. However, there were no significant correlations between the expression levels of the CERS2 protein with bladder cancer grade/stage or between the IC50 values of cells treated with NDV and CERS2 expression. Although the utility of CERS2 expression may be limited, its potential as an antimigration cancer therapeutic should be further examined.

Factors Determining the Increased Risk of Falls in Individuals With Knee Pain in the Malaysian Elders Longitudinal Research (MELoR) Study.

Objectives: While the negative impact of falls in older persons has been recognized, the association between knee pains and falls remains inconclusive due to underreporting and undertreatment of knee pain. This study was conducted to evaluate the relationship between knee pain and knee pain severity with falls risk and to further determine factors which influence this potential relationship. Design: This was cross-sectional study from the Malaysian Elders Longitudinal Research (MELoR) study. Setting: Urban community dwellers in a middle-income South East Asian country. Participants: One thousand two hundred twelve of a representative sample of community dwelling older persons aged 55 years and older. Outcome measures: Falls in the preceding 12 months and knee pain were collected during a home-based computer-assisted interview. Physical and functional performance were measured using the Timed Up and Go test and the Katz and Lawton scales, respectively. Psychological status was determined using the Depression Anxiety and Stress Scale (DASS-21). Results: Of the 1,212 participants included in this analysis, knee pain was present in 402 (33.17%) individuals (124 (30.85%) mild, 210 (52.24%) moderate, 68 (16.92%) severe). The presence of knee pain was associated with increased risk of falls [odds Ratio, OR(95% confidence interval, CI): 1.81 (1.37-2.38)]. Severe knee pain was an independent predictor for falls after adjustment for functional impairment and psychological status. Mild, moderate, and severe knee pain had a specific indirect effect on falls through reducing functional impairment, which in turn increases their psychological concern. Conclusion: Future studies should explore this relationship prospectively and evaluate whether interventions which alleviate psychological concerns and improve function will reduce falls risk in those with mild to moderate knee pain.

Prostate cancer in Asia: design of a patient registry to inform real-world treatments, outcomes, and quality of life.

BACKGROUND: The incidence of prostate cancer (PC) in Asian countries is increasing for reasons that are not clear. Data describing how PC is diagnosed and treated are fragmented across Asia, with marked intercountry and intracountry differences in outcome and knowledge gaps in clinical diagnostic and treatment practices. To address these knowledge gaps, we have established a PC disease registry with the aim of providing a comprehensive picture of PC diagnosis, prognosis, treatment and outcome, population characteristics, and comorbidities in real-world clinical practice in Asia. METHODS: This is a multinational, multicenter, longitudinal, and observational registry of PC patients presenting to participating tertiary-care hospitals in eight Asian countries (www.clinicaltrials.gov NCT02546908. Registry Identifier: NOPRODPCR4001). Approximately 3500-4000 eligible patients with existing or newly diagnosed high-risk localized PC (cohort 1), nonmetastatic biochemically recurrent PC (cohort 2), or metastatic PC (cohort 3) will be consecutively enrolled and followed-up for 5 years. An enrollment cap of 600 patients each will be applied to cohorts 1 and 2. Disease status is collected at enrollment, and outcome variables captured at 3-monthly intervals include diagnostic/staging, treatments including reason for change, laboratory results, comorbidities, and concomitant medications. Treatments and survival outcomes will be captured real time until study end. Patient-reported quality-of-life will be measured every 6 months, and medical resource utilization summarized at study end. Data analysis will include exploratory analyses of potential associations between multiple risk factors and socioeconomic variables with disease progression and evaluation of various treatments for PC including novel therapies on clinical outcome and health-related quality-of-life outcomes. RESULTS: 3636 men with PC were enrolled until July 2018; 416 in cohort 1, 399 in cohort 2 and 2821 in cohort 3. DISCUSSION: A total of 3636 patients were enrolled until July 2018. The prospective disease registry will provide comprehensive and wide-ranging real-world information on how PC is diagnosed and treated in Asia. Such information can be used to inform policy development for best practice and direct clinical study design evaluating new treatments.