Introduction: Prostate cancer is a heterogenous disease and the mechanisms that drive it to behave differently are not well understood. Tumour expression of the ERG oncogene occurs in the majority of patients with prostate cancer in Western studies. This is considered to be oncogenic as ERG acts as a transcription factor to regulate genes involved in tumour proliferation and invasion. In this study we investigated expression of ERG in Malaysian men with prostate cancer. Methods: Tissues were collected from 80 patients with clinically detected prostate cancer and treated with radical prostatectomy. Cases were tested for ERG by immunohistochemistry using the mouse monoclonal antibody EP111. All blocks on 48 cases were tested in order to determine the extent of heterogeneity of ERG expression within individual cases. ERG expression was analysed in relation to patient age, ethnicity and tumour stage and grade. Results: Forty-six percent of cases were ERG positive. There was no significant association between ERG and tumour grade or stage. Sixty-nine percent of Indian patients had ERG positive tumours; this was significantly higher (p=0.031) than for Chinese (40%) and Malay (44%) patients. Heterogeneity of ERG expression, in which both positive and negative clones were present, was seen in 35% of evaluated cases. Evaluation by tumour foci showed younger patients had more ERG positive tumour foci than older patients (p=0.01). Indian patients were more likely to have the majority of tumour foci with ERG staining positively, compared to either Chinese or Malay patients (P <0.01). Conclusion: In this study, tumour expression of ERG was more likely to occur in patients of Indian ethnicity.
ethnic variation

Heat shock proteins (HSPs) are a family of evolutionary conserved proteins that work as molecular chaperones for cellular proteins essential for cell viability and growth as well as having numerous cyto-protective roles. They are sub-categorised based on their molecular weights; amongst which some of the most extensively studied are the HSP90 and HSP70 families. Important members of these two families; Heat shock proteins 70 and heat shock proteins 90 (Hsp70/90), are the glucose regulated proteins (GRP). These stress-inducible chaperones possess distinct roles from that of the other HSPs, residing mostly in the endoplasmic reticulum and mitochondria, but they can also be translocated to other cellular locations. Their ability in adapting to stress conditions in the tumour microenvironment suggests novel functions in cancer. GRPs have been implicated in many crucial steps of carcinogenesis to include stabilization of oncogenic proteins, induction of tumour angiogenesis, inhibition of apoptosis and replicative senescence, and promotion of invasion and metastasis.

Introduction: Polymorphic expression of a CAG repeat sequence in the androgen receptor (AR) gene may influence the activity of the AR and the occurrence of prostate cancer and the TMPRSS2-ERG fusion event. Furthermore, this polymorphism may be responsible for the ethnic variation observed in prostate cancer occurrence and expression of the ERG oncogene. We investigate the expression of AR and ERG in the biopsies of Malaysian men with prostate cancer and in the same patients relate this to the length of the CAG repeat sequence in their AR gene. Materials and Methods: From a PSA screening initiative, 161 men were shown to have elevated PSA levels in their blood and underwent prostatic tissue biopsy. DNA was extracted from the blood, and exon 1 of the AR gene amplified by PCR and sequenced. The number of CAG repeat sequences were counted and compared to the immunohistochemical expression of ERG and AR in the matched tumour biopsies. Results: Of men with elevated PSA, 89 were diagnosed with prostate cancer, and 72 with benign prostatic hyperplasia (BPH). There was no significant difference in the length of the CAG repeat in men with prostate cancer and BPH. The CAG repeat length was not associated with; age, PSA or tumour grade, though a longer CAG repeat was associated with tumour stage. ERG and AR were expressed in 36% and 86% of the cancers, respectively. There was no significant association between CAG repeat length and ERG or AR expression. However, there was a significant inverse relationship between ERG and AR expression. In addition, a significantly great proportion of Indian men had ERG positive tumours, compared to men of Malay or Chinese descent. Conclusions: CAG repeat length is not associated with prostate cancer or expression of ERG or AR. However, ERG appears to be more common in the prostate cancers of Malaysian Indian men than in the prostate cancers of other Malaysian ethnicities and its expression in this study was inversely related to AR expression.

Asthma action plan (AAP) is an essential component of asthma education and self-management. AAPs provide patients with instructions on how to recognise loss of asthma control and the appropriate treatment steps. The use of AAP improves asthma-related quality of life and reduces the risk of asthma exacerbation. Despite its benefits, utilisation of AAP is disappointingly low both locally and worldwide. This review highlights the importance of AAP as part of an asthma care plan and provides practical information on the prescription of AAPs. We conclude by identifying possible barriers to AAP implementation and how these may be overcome.

INTRODUCTION: Effectiveness of COVID-19 control interventions relies significantly on behavioural modifications of its population. Differing adoption rates impacts subsequent COVID-19 control. Hence, positive and sustained behavioural modification is essential for disease control. We describe the adoption rates of behavioural modifications for Singapore's "circuit-breaker" (CB), the national public health response to the COVID-19 crisis, among the general population in the community. METHODS: We conducted an interrupted-time series study using retrospective secondary data. We compared the proportion of Singaporeans who reported adopting specific behaviour modifications before, during and after CB. Behaviours of interest were working from home, performing hand hygiene, using face mask in public, and avoiding crowded areas. We compared change in incidence rates for community COVID-19 cases among the general population across the same time periods. RESULTS: There was an increase in face mask usage (+46.9%, 95% confidence interval [CI] 34.9-58.8, CONCLUSION Community incidence of COVID-19 in Singapore decreased during CB and remained low after CB. Use of face masks and social-distancing compliance through working from home increased during CB. However, it is unlikely to influence other sources of COVID-19 such as imported cases or within foreign worker dormitories.
Adoption ; COVID-19 ; Humans ; Retrospective Studies ; SARS-CoV-2 ; Singapore/epidemiology*

No abstract available.
Drug-Induced Liver Injury ; Ribavirin

PURPOSE: Malnutrition is associated with an increased risk of developing complications following gastrointestinal surgery, especially following radical surgeries such as pelvic exenteration. This study aims to determine if preoperative body mass index (BMI) is associated with 30-day morbidity, length of hospital stay and/or quality of life (QoL) in patients undergoing pelvic exenteration surgery for recurrent and locally-advanced rectal cancer prior to a prospective trial. METHODS: A review of all patients who underwent pelvic exenteration surgery prior to 2008 was performed. Patients were included if they had a documented BMI as well as a QoL measurement (Functional Assessment Cancer Therapy - Colorectal questionnaire). RESULTS: Thirty-one patients, with a mean age of 56 years, had preoperative height and weight data, as well as measures of postoperative QoL, and formed the study group. The numbers of patients with recurrent (n = 17) or locally-advanced rectal cancer (n = 14) were similar. The mean length of stay was 21 days while the mean BMI of the patients was 24.3 (+/- 5.9) kg/m2. The majority of the patients were either of normal weight (n = 15) or overweight/obese (n = 11). The average length of hospital stay was significantly longer in patients who were underweight compared to those who were of normal weight (F = 6.508, P = 0.006) and those who were overweight and obese (F = 6.508, P = 0.007). CONCLUSION: This study suggests that a lower body mass index preoperatively is associated with a longer length of hospital stay. BMI is not associated with long-term QoL in this patient group. However, further prospective research is required.
Body Mass Index* ; Humans ; Length of Stay* ; Malnutrition ; Overweight ; Pelvic Exenteration* ; Quality of Life* ; Rectal Neoplasms* ; Thinness ; Treatment Outcome

INTRODUCTION: The cost-effectiveness of screening asymptomatic non-alcoholic fatty liver disease (NAFLD) patients remains debatable, with current studies assuming lifelong benefits of NAFLD screening while neglecting cardiovascular outcomes. This study aims to assess the cost-effectiveness of NAFLD screening among type 2 diabetes mellitus (T2DM) patients, and to establish a price threshold for NAFLD treatment, when it becomes available. METHOD: A Markov model was constructed comparing 4 screening strategies (versus no screening) to identify NAFLD with advanced fibrosis among T2DM patients: fibrosis-4 (FIB-4), vibration-controlled transient elastography (VCTE), FIB-4 and VCTE (simultaneous), and FIB-4 and VCTE (sequential). Sensitivity analyses and price threshold analyses were performed to assess parameter uncertainties in the results. RESULTS: VCTE was the most cost-effective NAFLD screening strategy (USD24,727/quality-adjusted life year [QALY]), followed by FIB-4 (USD36,800/QALY), when compared to no screening. Probabilistic sensitivity analysis revealed a higher degree of certainty for VCTE as a cost-effective strategy compared to FIB-4 (90.7% versus 73.2%). The duration of expected screening benefit is the most influential variable based on incremental cost-effectiveness ratio tornado analysis. The minimum duration of screening benefit for NAFLD screening to be cost-effective was at least 2.6 years. The annual cost of NAFLD treatment should be less than USD751 for NAFLD screening to be cost-effective. CONCLUSION Both VCTE and FIB-4 are cost-effective NAFLD screening strategies among T2DM patients in Singapore. However, given the lack of access to VCTE at primacy care and potential budget constraints, FIB-4 can also be considered for NAFLD screening among T2DM patients in Singapore.
Humans ; Non-alcoholic Fatty Liver Disease/diagnosis* ; Cost-Benefit Analysis ; Diabetes Mellitus, Type 2/diagnosis* ; Research ; Fibrosis