High resolution front-side visualization of charge stored in EEPROM with scanning nonlinear dielectric microscopy (SNDM).

By exposing floating gates of EEPROM memory cells with frontside sample preparation, scanning nonlinear dielectric microscopy (SNDM) succeeded in reading back the data stored in the memory cells with a 250 nm node size. At an optimized voltage bias of AC = 3 V and DC = 1 V, a clear signal contrast between programmed and erased cells is obtained. The high resolution SNDM signal reveals the details of bowling-pin shape structure of memory cells, providing high confidence in data assignment during forensic applications. Such high resolution also makes SNDM a promising technique for newer generation devices with smaller node size.

The life and health challenges of young Malaysian couples: results from a stakeholder consensus and engagement study to support non-communicable disease prevention.

BACKGROUND: Malaysia faces burgeoning obesity and diabetes epidemics with a 250% and 88% increase respectively between 1996 and 2006. Identifying the health challenges of young adults in Malaysia, who constitute 27.5 % of the population, is critical for NCD prevention. The aim of the study was two-fold: (1) to achieve consensus amongst stakeholders on the most important challenge impacting the health of young adults, and (2) to engage with stakeholders to formulate a NCD prevention framework. METHODS: The Delphi Technique was utilised to achieve group consensus around the most important life and health challenges that young adults face in Malaysia. Subsequently, the results of the consensus component were shared with the stakeholders in an engagement workshop to obtain input on a NCD prevention framework. RESULTS: We found that life stress was a significant concern. It would seem that the apathy towards pursuing or maintaining a healthy lifestyle among young adults may be significantly influenced by the broader distal determinant of life stress. The high cost of living is suggested to be the main push factor for young working adults towards attaining better financial security to improve their livelihood. In turn, this leads to a more stressful lifestyle with less time to focus on healthier lifestyle choices. CONCLUSIONS: The findings highlight a pivotal barrier to healthier lifestyles. By assisting young adults to cope with daily living coupled with realistic opportunities to make healthier dietary choices, be more active, and less sedentary could assist in the development of NCD health promotion strategies.

Phenolic Michael reaction acceptors: combined direct and indirect antioxidant defenses against electrophiles and oxidants.

The implications of oxidative stress in the pathogenesis of many chronic human diseases has led to the widely accepted view that low molecular weight antioxidants could be beneficial and postpone or even prevent these diseases. Small molecules of either plant or synthetic origins, which contain Michael acceptor functionalities (olefins or acetylenes conjugated to electron-withdrawing groups) protect against the toxicity of oxidants and electrophiles indirectly, i.e., by inducing phase 2 cytoprotective enzymes. Some of these molecules, e.g., flavonoid and curcuminoid analogues that have phenolic hydroxyl groups in addition to Michael acceptor centers, are also potent direct antioxidants, and may therefore be appropriately designated: bifunctional antioxidants. By use of spectroscopic methods we identified phenolic chalcone and bis(benzylidene)acetone analogues containing one or two Michael acceptor groups, respectively, as very efficient scavengers of two different types of radicals: (a) the nitrogen-centered 2,2'-azinobis-(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS.+) radical cation, and (b) the oxygen-centered galvinoxyl (phenoxyl) radical. The most potent scavengers are those also bearing hydroxyl substituents on the aromatic ring(s) at the ortho-position(s). The initial reaction velocities are very rapid and concentration-dependent. In the human keratinocyte cell line HaCaT, the same compounds coordinately increase the intracellular levels of glutathione, glutathione reductase, and thioredoxin reductase. Thus, such bifunctional antioxidants could exert synergistic protective effects against oxidants and electrophiles which represent the principal biological hazards by: (i) scavenging hazardous oxidants directly and immediately; and (ii) inducing the phase 2 response to prevent and resolve the consequences of hazardous processes that are already in progress, i.e., acting indirectly, but with much more diverse and long-lasting effects.

Choice of antihypertensive drug in the diabetic patient.

The hypertensive patient with type 2 diabetes is especially at risk of adverse cardiovascular events. The United Kingdom Prospective Diabetes Study (UKPDS) and Hypertension Optimal Treatment (HOT) studies suggested that treatment to a lower target blood pressure resulted in better prevention of clinical disease in these patients. Most trials comparing antihypertensive drugs have shown only minimal differences between the various agents. The evidence from the trials suggests that diuretics, beta-blockers, calcium channel blockers (CCBs), angiotensin-converting enzyme (ACE) inhibitors, and the angiotensin-receptor antagonists (ARBs) will all successfully reduce adverse clinical events. The largest of the comparative hypertensive drug trials, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), demonstrated that a diuretic has a better hypotensive effect, and was more successful in preventing many aspects of cardiovascular disease compared with CCBs and ACE inhibitors. The importance of good blood pressure control and the general equivalence of antihypertensive drugs were again shown in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial, which compared an ARB with a CCB. Choice of antihypertensive agent should be individualized and guided by the presence of concomitant clinical disease and the need to protect any specific target organ system in the diabetic hypertensive. Diuretics, being potent hypotensive drugs with clearly demonstrated clinical benefit, should form part of the antihypertensive regimen of most diabetic hypertensives. ACE inhibitors and ARBs are especially useful in preventing nephropathy. Most patients will require a combination of antihypertensive drugs to achieve tight blood pressure control of under 130/80 mm Hg in the diabetic hypertensive. The clinician should concentrate on seeking this lower target blood pressure rather than be excessively concerned about which is the best antihypertensive agent.

Milestones of the medical school and medical progress of Singapore over the past 100 years.

The Medical School started off in an old female lunatic asylum on the site of the general hospital at Sepoy Lines. It was founded on 3 July 1905 and was called the Straits and Federated Malay States Government Medical School. In 1916, the Licentiate in Medicine and Surgery (LMS) was recognised fully by the General Medical Council of Britain as a registrable qualification. In 1921, the medical school was renamed King Edward VII College of Medicine to reflect its academic status. In 1926, the College and its hospitals were inspected by Sir Richard Needham, who had been sent by the General Medical Council of Great Britain. In his report, he told the Council that in his opinion, the graduates should be given the MBBS degree because of the high standard of the Medical School. The medical school was closed by the Japanese on 16 February 1942. After the end of World War II, the College of Medicine resumed classes in June 1946. In 1962, the medical faculty became the Faculty of Medicine of the University of Singapore. From 1984 to 1986, following the university's move to Kent Ridge, the Faculty's clinical school also moved to the National University Hospital. In 2004, plans were well underway for the opening of the country's second medical school on the grounds of the Singapore General Hospital.

The first graduates in 1910.

The Medical School in Singapore was founded on 3 July 1905 and named the Straits and Federated Malay States Government Medical School. There were 23 students in the first enrollment; 16 students attended the full course, while 7 attended a 2-year course for hospital assistants. The pioneer group of 7 that graduated in May 1910 (the Magnificent Seven) consisted of Drs Chen Su Lan, Edwin Williborod deCruz, and John Gnanapragasam from Singapore; Drs Willie Carnegie and Mark W Chill from Penang; Dr SR Krishnan from Seramban and Dr John Scott Lee from Ipoh. In December 1910, a further 6 students graduated. Of this first batch of 13 graduates in 1910, we describe the careers of 6; no records exist of the remaining 7.

Absence of ion channels CACN1AS and SCN4A mutations in thyrotoxic hypokalemic periodic paralysis.

Muscle weakness in patients with thyrotoxicosis during hypokalemic episodes (thyrotoxic periodic paralysis [TPP]) occurs sporadically and mostly in males. It is treated by infusion or oral supplementation with potassium and with resolution of the thyrotoxicosis state. The clinical features of TPP resemble familial hypokalemic periodic paralysis (hypoKPP), which has been linked to two mutations in the gene encoding the skeletal muscle calcium channel alpha-1 subunit (CACN1AS; Arg528His and Arg1239His) and to the sodium channel alpha-subunit (SCN4A; Arg672His). We screened for the mutations (CACN1AS by polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP]; SCN4A by single-strand conformation polymorphism analysis) described in hypoKPP in 20 unrelated patients with documented episodes of TPP (mean age, 40.0 +/- 12.3 years 19 males). Forty-eight patients with hyperthyroidism resulting from Graves' disease (48.5 +/- 12.3 years; 13 males), 1 patient with idiopathic hypoKPP (a 32-year-old male) and 32 healthy subjects (41.0 +/- 19.1 years; 16 males) were included. We found none of the TPP patients carry CACN1AS and SCN4A mutations. The hyperthyroid patients and control subjects were also negative for the mutations. The patient with idiopathic hypoKPP was genotyped to have the Arg528His mutation. These results suggest that despite close similarities between TPP and hypoKPP, a likely genetic basis for TPP does not involve the same gene mutations associated with hypoKPP.

Hereditary spherocytosis, a pitfall in the assessment of glycaemic control.

The use of glycosylated haemoglobin in the assessment of diabetic control is ubiquitous. Hereditary spherocytosis is a haemolytic anaemia with shortened red blood cell lifespan, which can interfere with the methods of glycosylated haemoglobin measurement. We report a case of hereditary spherocytosis in a young man with type 1 diabetes, and illustrate the discrepancy in the measurements of glycosylated haemoglobin, which were inconsistent with the blood glucose profiles. Fructosamine, an alternative time-averaged indicator of blood glucose level, was advantageous in this particular situation. The awareness of the limitations of glycosylated haemoglobin is essential in the clinical care of patients with diabetes, which is a major health problem in Singapore.

IgG1 subclass dominates autoimmune response to tyrosine phosphatase-like molecule IA-2 in Chinese type 1 diabetes patients.

BACKGROUND AND AIMS: Islet autoantibodies are known markers for type 1 diabetes with an immune-mediated basis; their isotype or subclass profiles may also provide clues to changes in immune response during disease or after intervention. For ICAs and GADab, the IgG1 subclass consistently dominates in recent-onset disease. The aims of our study were to determine the isotype patterns for IA-2ab in Asian Chinese patients with autoimmune diabetes. MATERIALS AND METHODS: From an initial screening of over 400 diabetes patients, 40 subjects (mean age 22.2 +/- 15.8 years) with IA-2ab were enrolled for this study. IA-2ab was detected by radioimmunoassay of [35S]-labelled recombinant human IA-2 ic(605 - 979). Of them, 31 (median age 15 years, range 2 - 57 years; 16 children) had clinical type 1 diabetes (that is, they required insulin at onset or within 1 year) with the majority having been recently diagnosed (< 1 year). The other 9 patients had clinical type 2 diabetes phenotype. RESULTS: IA-2ab IgG subclasses determined with monospecific secondary antibodies showed that both type 1 diabetic adults and children had similarly non-restricted isotype patterns with a strong presence of IgG1-IA-2ab. The rank order was IgG1 > 3 > 2 > 4; 15 subjects had detectable IgG4-IA-2ab. Clonality of immune response determined with kappa/lambda chain-specific antibodies also showed a non-restricted pattern. Patients aged 38.2 +/- 15.2 years with type 2 diabetes had broad patterns of isotypes - IgG1/3 was detected more frequently (n = 8) than IgG2/4 (n = 5). Of three patients on insulin treatment, one was also positive for GADab. The remaining 6 patients were on oral hypoglycaemic treatment. IA-2ab in type 2 diabetes showed a low titre compared to type 1 diabetes. CONCLUSIONS: Isotype responses to IA-2 had a strong IgG1 presence, similar to ICAs and GADab. With IgG3 subclass representation, a predominant Th1 milieu in the systemic environment is likely. There is no suggestion of differences in immune response to IA-2 between adults and children with type 1 diabetes.

Stroke disease management--a framework for comprehensive stroke care.

Disease management is an approach to patient care that coordinates medical resources for the patient across the entire healthcare delivery system throughout the lifetime of the patient with the disease. Stroke is suitable for disease management as it is a well-known disease with a high prevalence, high cost, variable practice pattern, poor clinical outcome, and managed by a non-integrated healthcare system. It has measurable and actionable outcomes, with available local expertise and support of the Ministry of Health. Developing the programme requires a multidisciplinary team, baseline data on target populations and healthcare services, identification of core components, collaboration with key stakeholders, development of evidence-based clinical practice guidelines and carepaths, institution of care coordinators, use of information technology and continuous quality improvement to produce an effective plan. Core components include public education, risk factor screening and management, primary care and specialist clinics, acute stroke units, inpatient and outpatient rehabilitation facilities, and supportive community services including medical, nursing, therapy, home help and support groups for patients and carers. The family physician plays a key role. Coordination of services is best done by a network of hospital and community-based care managers, and is enhanced by a coordinating call centre. Continuous quality improvement is required, with audit of processes and outcomes, facilitated by a disease registry. Pitfalls include inappropriate exclusion of deserving patients, misuse, loss of physician and patient independence, over-estimation of benefits, and care fragmentation. Collaboration and cooperative among all parties will help ensure a successful and sustainable programme.

Implementing chronic disease management in the public healthcare sector in Singapore: the role of hospitals.

The public health care delivery system in Singapore faces the challenges of a rapidly ageing population, an increasing chronic disease burden, increasing healthcare cost, rising expectations and demand for better health services, and shortage of resources. It is also fragmented, resulting in duplication and lack of coordination between institutions. A disease management approach has been adopted by the National Healthcare Group (NHG) as a critical strategy to provide holistic, cost-effective, seamless and well-coordinated care across the continuum. The framework in the development of the disease management plan included identifying the diseases and defining the target population, organizing a multi-disciplinary team lead by a clinician champion, defining the core components, treatment protocols and evaluation methods, defining the goals, and measuring and managing the outcomes. As disease management and case management for chronic diseases are new approaches adopted in the healthcare delivery system, there is a lack of understanding by healthcare professionals. The leadership and participation of hospital physicians was sought in the planning, design and outcomes monitoring to ensure their 'buy-in' and the successful implementation and effectiveness of the program. The episodic diagnosis related group (DRG)-based framework of funding and subvention for healthcare, and the shortage of step-care care facilities, have been recognized by the Ministry of Health as an impediments to the implementation, and these are currently being addressed.

Development and implementation of a clinical pathway programme in an acute care general hospital in Singapore.

A critical or clinical pathway defines the optimal care process, sequencing and timing of interventions by doctors, nurses and other health care professionals for a particular diagnosis or procedure. Clinical pathways are developed through collaborative efforts of clinicians, case managers, nurses, pharmacists, physiotherapists and other allied health care professionals with the aim of improving the quality of patient care, while minimizing cost to the patient. The use of clinical pathways has increased over the past decade in the USA, the UK, Australia, and many other developed countries. However, its use in the developing nations and Asia has been sporadic. To the author's knowledge, there is to date, no published literature on the use and impact of clinical pathways on the quality and cost of patient care in the Asian health care setting. This paper provides a qualitative account of the development and implementation of a clinical pathway programme (using the example of patients with uncomplicated acute myocardial infarction) in an acute care general hospital in Singapore. The paper concludes that clinical pathways, when implemented in the context of an acute care hospital, can result in improvements in the care delivery process.