Mbd3 (Methyl-CpG binding domain protein), a core member of NuRD (nucleosome remodelling and deacetylation) is essential for embryogenesis. However, its role in reprogramming of somatic cells into induced pluripotent stem cells (iPSC) remains controversial. Some reports suggest that Mbd3 inhibits pluripotency, whilst others show that it greatly enhances reprogramming efficiency. Our study is the first to assess the role of Mbd3 on reprogramming of primary human fibroblasts using Yamanaka episomal plasmids (Reprogramming factors (RF) under feeder-free conditions. We showed that shRNA-mediated partial depletion of Mbd3 resulted in >5-fold reduction in the efficiency of reprogramming of primary human fibroblasts. Furthermore, iPSC that emerged after knock-down of Mbd3 were incapable of trilineage differentiation even though they expressed all markers of pluripotency. In contrast, over-expression of the Mbd3b isoform along with the Yamanaka episomal plasmids increased the number of fibroblast derived iPSC colonies by at least two-fold. The resulting colonies were capable of trilineage differentiation. Our results, therefore, suggest that Mbd3 appears to play an important role in reprogramming of primary human fibroblasts, which provides further insight into the biology of reprogramming but also has direct implication for translation of iPSC to clinic.
Biology ; Embryonic Development ; Female ; Fibroblasts ; Humans ; Induced Pluripotent Stem Cells ; Plasmids ; Pregnancy

Although gastroesophageal reflux disease is not as common in Asia as in western countries, the prevalence has increased substantially during the past decade. Gastroesophageal reflux disease is associated with considerable reductions in subjective well-being and work productivity, as well as increased healthcare use. Proton pump inhibitors (PPIs) are currently the most effective treatment for gastroesophageal reflux disease. However, there are limitations associated with these drugs in terms of partial and non-response. Dexlansoprazole is the first PPI with a dual delayed release formulation designed to provide 2 separate releases of medication to extend the duration of effective plasma drug concentration. Dexlansoprazole has been shown to be effective for healing of erosive esophagitis, and to improve subjective well-being by controlling 24-hour symptoms. Dexlansoprazole has also been shown to achieve good plasma concentration regardless of administration with food, providing flexible dosing. Studies in healthy volunteers showed no clinically important effects on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition, with no dose adjustment of clopidogrel necessary when coprescribed. This review discusses the role of the new generation PPI, dexlansoprazole, in the treatment of gastroesophageal reflux disease in Asia.
Asia* ; Blood Platelets ; Delayed-Action Preparations ; Delivery of Health Care ; Dexlansoprazole* ; Efficiency ; Esophagitis ; Gastroesophageal Reflux* ; Healthy Volunteers ; Plasma ; Prevalence ; Proton Pump Inhibitors ; Proton Pumps* ; Protons*

INTRODUCTIONThis study investigated the effect of an access-enhanced intervention on hypertension screening and management, as well as on health behaviours among newly diagnosed hypertensives, in a multi-ethnic low socioeconomic status (SES) community. Factors associated with hypertension screening, treatment, and control in the community were also determined.

MATERIALS AND METHODSThe study involved all residents aged ≥40 years in 2 public rental housing precincts (low SES), between 2009 and 2011, who were followed-up prospectively for 1 year after a 6-month community-based intervention comprising a 3-month access-enhanced screening component and a 3-month follow-up (outreach) component. Blood pressure was measured at baseline and follow-up. Multivariate Cox regression determined predictors of hypertension management at follow-up.

RESULTSThe follow-up rate was 80.9% (467/577). At baseline, 60.4% (282/467) were hypertensive; 53.5% (151/282) were untreated; 54.2% (71/131) uncontrolled. One year later, postintervention, 51.6% (78/151) of untreated hypertensives were treated; combined with treated hypertensives previously uncontrolled, 53.0% (79/149) achieved control. Older age independently predicted treatment (adjusted relative risk, aRR = 1.98, CI, 1.08 to 3.65); majority ethnicity (aRR = 1.76, CI, 1.05 to 2.96), employment (aRR = 1.85, CI, 1.26 to 2.80) and newly treated hypertension (aRR=1.52, CI, 1.01 to 2.32) predicted control. A total of 52.4% (97/185) were irregularly screened at baseline; at follow-up 61.9% (60/97) were regularly screened. Cost and misperceptions were common barriers to screening and treatment. Newly diagnosed hypertensives were also less likely to go for additional cardiovascular screening (aRR = 0.54, CI, 0.29 to 0.99).

CONCLUSIONAn access-enhanced intervention had some success in improving hypertension management within low SES communities; however, it was less successful in improving cardiovascular risk management, especially in encouraging lifestyle changes and additional cardiovascular screening amongst newly diagnosed hypertensives.

Adult ; Age Factors ; Aged ; Antihypertensive Agents ; therapeutic use ; Asian Continental Ancestry Group ; statistics & numerical data ; Diet, Sodium-Restricted ; methods ; Exercise Therapy ; methods ; Female ; Health Services Accessibility ; statistics & numerical data ; Humans ; Hypertension ; diagnosis ; ethnology ; therapy ; Male ; Mass Screening ; Middle Aged ; Multivariate Analysis ; Patient Compliance ; ethnology ; statistics & numerical data ; Patient Dropouts ; statistics & numerical data ; Poverty ; statistics & numerical data ; Proportional Hazards Models ; Prospective Studies ; Risk Reduction Behavior ; Singapore ; Smoking Cessation ; methods ; Social Class ; Treatment Outcome ; Weight Reduction Programs ; methods

INTRODUCTIONPrompt recognition of cardiac arrest and initiation of cardiopulmonary resuscitation (CPR) and defibrillation is necessary for good outcomes from out-of-hospital cardiac arrest (OHCA). This study aims to describe the recognition and treatment of OHCA in patients conveyed by non-emergency ambulance services (EAS) in Singapore.

MATERIALS AND METHODSThis is a multi-centre, retrospective chart review, of cases presenting to public emergency departments (EDs), conveyed by non-EAS and found to be in cardiac arrest upon ED arrival. The study was from October 2002 to August 2009. The following variables were examined: ability to recognise cardiac arrest, whether CPR was carried out by the ambulance crew and whether an automated external defibrillator (AED) was applied.

RESULTSEighty-six patients were conveyed by non-EAS and found to be in cardiac arrest upon ED arrival. Mean age was 63 years (SD 21.8), 70.9% were males. A total of 53.5% of arrests occurred in the ambulance while 70.9% were found to be asystolic upon ED arrival. Seven patients had a known terminal illness. Survival to discharge was 3.5%. Cardiac arrest went unrecognised by the ambulance crew in 38 patients (44.2%). CPR was performed in 35 patients (40.7%) of the 86 patients and AED was applied in only 10 patients (11.6%).

CONCLUSIONWe found inadequate recognition and delayed initiation of treatment for OHCA. Possible reasons include a lack of training in patient monitoring and detection of cardiac arrest, lack of CPR training, lack of confidence in performing CPR, lack of AEDs on ambulances and lack of training in their use.

Aged ; Aged, 80 and over ; Ambulances ; Cardiopulmonary Resuscitation ; standards ; Electric Countershock ; standards ; Emergency Medical Services ; standards ; Female ; Humans ; Male ; Middle Aged ; Out-of-Hospital Cardiac Arrest ; diagnosis ; therapy ; Retrospective Studies ; Singapore ; Transportation of Patients ; standards

Autistic Disorder ; complications ; psychology ; Child ; Child Development ; Communication ; Down Syndrome ; complications ; physiopathology ; psychology ; Follow-Up Studies ; Humans ; Interpersonal Relations ; Male ; Play and Playthings ; Singapore ; Social Behavior ; Stress, Psychological ; psychology

INTRODUCTIONThis study aimed to describe the patterns of sedative use among terminally ill cancer patients who were referred to a hospital-based specialist palliative care service for symptom management. It also aimed to examine whether sedative use among terminally ill cancer patients during the last two days of life had any impact on their survival.

METHODSA retrospective review of case notes was carried out for patients with a diagnosis of terminal cancer, who died in a 95-bedded oncology ward between September 2006 and September 2007. Data was collected on patient characteristics, duration of palliative care, indications and doses of sedatives used at 48 hours and 24 hours before death.

RESULTSA total of 238 patients died while receiving specialist palliative care, 132 of whom (55.5%) were female. At 48 hours and 24 hours before death, 22.6% and 24.8% of patients, respectively, were on sedatives like midazolam, haloperidol or both. The median dose of midazolam was 5 mg/day while the haloperidol dose at 48 hours and 24 hours before death was 3 mg/day and 4 mg/day, respectively. The indications for midazolam were anxiety, breathlessness and stiffness, while those for haloperidol were confusion agitation and nausea. Survival analysis showed no significant difference in survival between patients who were on sedatives and those who were not. The p-value for log-rank test was 0.78.

CONCLUSIONThe results showed that the doses and overall frequency of sedative use in this patient population tended to be low and that usage of sedatives had no deleterious influence on survival.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Analgesics, Opioid ; therapeutic use ; Female ; Haloperidol ; therapeutic use ; Humans ; Hypnotics and Sedatives ; therapeutic use ; Male ; Midazolam ; therapeutic use ; Middle Aged ; Neoplasms ; drug therapy ; mortality ; Palliative Care ; methods ; Retrospective Studies ; Terminal Care ; methods ; Terminally Ill ; Time Factors ; Treatment Outcome

INTRODUCTIONMore than half of all deaths in Singapore occur in hospitals. Little is known about the quality of care received by dying patients in hospitals. The Liverpool Care Pathway (LCP) provides a framework of providing good end-of-life care for dying patients and has been used with success in the United Kingdom (UK). In this study, we investigate whether adoption of a modified LCP in a Singapore hospital translated to better end-of-life care for cancer patients.

MATERIALS AND METHODSThe LCP was adapted and implemented as a pilot project on an oncology ward in Singapore General Hospital. A baseline review of 30 consecutive death records was performed, followed by a 4-month pilot and post-implementation audit of 30 consecutive patients on the adapted LCP.

RESULTSFive types of end-of-life symptoms were analysed. There was only 1 uncontrolled symptom at death in the post-implementation group compared to 24 uncontrolled symptoms in the retrospective audit group. The prescription of breakthrough medications for symptom control increased from 21% in the retrospective audit group to 79% in the post-implementation group. Inappropriate monitoring was discontinued in 25 patients in the post-implementation group compared to none in the retrospective audit group. The documentation of resuscitation status and religion of the patient was improved, achieving full documentation in the post-implementation group.

CONCLUSIONThis study shows promising results for improving end-of-life care in cancer patients with a protocol-based pathway in a Singapore hospital. Extension of this care pathway to other settings should be explored to maximise its benefits to patients dying from all causes in hospital.

Critical Pathways ; standards ; Diffusion of Innovation ; Female ; Hospital Mortality ; Hospitals, Public ; Humans ; Male ; Medical Audit ; Middle Aged ; Neoplasms ; Quality Improvement ; Retrospective Studies ; Singapore ; Terminal Care ; standards ; Tertiary Care Centers ; United Kingdom

INTRODUCTIONThis study aims to determine if the quantitative method of region-of-interest (ROI) analysis of lesion attenuation on CT may be a useful adjunct to the conventional approach of diagnosis by visual assessment in assessing tracer wash-out in hepatocellular carcinomas.

MATERIALS AND METHODSFrom a surgical database of 289 patients from 2 institutions, all patients with complete surgical, pathological and preoperative multiphasic CT scans available for review were selected. For each phase of scanning, HU readings of lesion obtained (Lesion(arterial), Lesion(PV) and Lesion(equilibrium)) were analysed using receiver operating curves (ROC) to determine the optimal method and cut-off value for quantitative assessment of tumour wash-out (Lesion(arterial - equilibrium), Lesion(PV - equilibrium) or Lesion(peak - equilibrium)).

RESULTSNinety-four patients with one lesion each met the inclusion criteria. The area under the curve (AUC) values for Lesion(arterial - equilibrium) (0.941) was higher than the AUC for Lesion(pv - equilibrium) (0.484) and for Lesion(peak - equilibrium) (0.667). Based on ROC analysis, a cut-off of 10HU value for Lesion(arterial - equilibrium) would yield sensitivity and specificity of 91.5% and 80.9%, respectively. ROI analysis detected 9/21 (42.9%) of lesions missed by visual analysis. Combined ROI and visual analysis yields a sensitivity of 82/94 (87.2%) compared to 73/94 (77.7%) for visual analysis alone.

CONCLUSIONUsing a cut-off of 10 HU attenuation difference between the arterial and equilibrium phases is a simple and objective method that can be included as an adjunct to visual assessment to improve sensitivity for determining lesion wash-out on CT.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular ; diagnosis ; pathology ; surgery ; Confidence Intervals ; Databases, Factual ; Female ; Humans ; Liver ; pathology ; Liver Neoplasms ; diagnosis ; pathology ; surgery ; Male ; Middle Aged ; Preoperative Period ; ROC Curve ; Retrospective Studies ; Sensitivity and Specificity ; Tomography, X-Ray Computed ; instrumentation ; Young Adult

Background: Neuropathic symptoms and signs are common in the elderly and are often considered normal fi ndings. However, symptomatic polyneuropathy may contribute to disability and falls in the elderly. The prevalence of peripheral neuropathy in the elderly in Malaysia has not been previously reported. The objective of this pilot study is to determine the frequency of symptomatic sensory polyneuropathy in a group of elderly subjects in the community and their possible associated factors. Methods: Cross sectional survey of subjects aged 65 years and above, carried out in an urban neighbourhood in Petaling Jaya. Using a standardised questionnaire, subjects were asked about sensory neuropathic symptoms, associated medical conditions and social habits. They were examined for the ankle refl ex, vibration, joint position, and pinprick sensations. Possible symptomatic sensory polyneuropathy was defi ned as bilateral distal neuropathic symptoms, loss of pinprick sensation and proprioception sense. Results: Of the 100 subjects, 63% had neuropathic symptoms and signs and 20% had possible symptomatic sensory polyneuropathy. Subjects with polyneuropathy complained of more postural instability and giddiness and distal weakness. Diabetes mellitus was associated with the presence of neuropathic symptoms and signs but not with polyneuropathy. Age was signifi cantly associated with polyneuropathy. Conclusion: The frequency of symptomatic sensory polyneuropathy in a group of elderly subj