INTRODUCTIONNeurological soft signs (NSS) are suggested as a candidate endophenotype for schizophrenia. This article aims to review relevant literature and discuss the role of NSS in understanding schizophrenia.

METHODSThis is an update on a review article published in 2003. Articles from 2003 onwards were specifically reviewed and discussed with relevance to the role of NSS as endophenotype for schizophrenia.

RESULTSConsistent data suggest an excess of NSS in schizophrenic patients. NSS appear to be related to schizophrenic symptoms, in particular negative symptoms and disorganisation. Information on NSS and demographic correlates is scarce, and the confounding effects between age, education and intelligence on NSS constitute an important gap in current knowledge. Longitudinal data suggest NSS as both a trait and state variable in the course of disease. NSS are not specific with regard to diagnosis, although there are claims that individual sub-components may be more specific. The weight of evidence raises question on the specificity of NSS for schizophrenia.

CONCLUSIONSThe usefulness and feasibility of NSS as a specific endophenotype target for schizophrenia is unclear. However, NSS remain an important feature and symptom correlate of schizophrenia. Future research should focus on delineating the effects of NSS from those of confounding demographic variables, and the stability of NSS over the course of illness to elucidate its role in schizophrenia.

Humans ; Mental Disorders ; Neurologic Examination ; Phenotype ; Risk Factors ; Schizophrenia ; diagnosis ; genetics ; Sensitivity and Specificity

The burn center in our hospital is a national and regional (Southeast Asia) center. Of all admissions, 10% are related to blast explosions, and 8% due to chemical burns. In the acute burn management protocol of Singapore General Hospital, early surgical debridement is advocated for all acute partial-thickness burns. The aim of early surgical debridement is to remove all debris and unhealthy tissue, preventing wound infection and thereby expediting wound healing. In chemical burns, there can be stubborn eschars that are resistant to traditional debridement. We would like to present a novel technique using the diathermy scratch pad as a cheap and efficient tool for the dual purpose of surgical debridement and dermabrasion.
Burn Units ; Burns ; Burns, Chemical ; Debridement ; Dermabrasion ; Diathermy ; Explosions ; Foreign Bodies ; Hospitals, General ; Singapore ; Wound Healing ; Wound Infection

The sudden outbreak of severe acute respiratory syndrome (SARS) in 2002 prompted the establishment of a global scientific network subsuming most of the traditional rivalries in the competitive field of virology. Within months of the SARS outbreak, collaborative work revealed the identity of the disastrous pathogen as SARS-associated coronavirus (SARS-CoV). However, although the rapid identification of the agent represented an important breakthrough, our understanding of the deadly virus remains limited. Detailed biological knowledge is crucial for the development of effective countermeasures, diagnostic tests, vaccines and antiviral drugs against the SARS-CoV. This article reviews the present state of molecular knowledge about SARS-CoV, from the aspects of comparative genomics, molecular biology of viral genes, evolution, and epidemiology, and describes the diagnostic tests and the anti-viral drugs derived so far based on the available molecular information.

Translational research (TR) can be defined as research where a discovery made in the laboratory (bench) can be applied in the diagnosis, treatment or prevention of a disease. Examples of medical discoveries contributing to translational medicine (TM) include the isolation of insulin by Banting (Nobel Laureate, 1923), the discovery of penicillin by Alexander Fleming (Nobel Laureate, 1945) and recently the discovery of the role of bacterium Helicobacter pylori in the causation of gastritis and peptic ulcer by Marshall and Warren (Nobel Laureates, 2005). Clinical research (CR) would be a more appropriate term for the bulk of research work undertaken by doctors. CR embraces both clinical based and laboratory-based research. The terminology "bedside to bench" applies more to CR as opposed to "bench to bedside" in the case of TR. But regardless of who does it, as long as the discovery can be translated to the bedside and results in improvement in patient care it can be considered a contribution to TM. Our work spans a 30-year period, involving laboratory-based research, clinical trials and genomics of IgA nephritis (Nx). This is a series of work to elucidate the pathogensis and therapy of IgANx. Plasma beta-thromboglobulin (BTG) an in-vivo index of platelet aggregation and anti-thrombin III increase due to a constant thrombogenecity resulting from platelet degranulation formed the basis for anti-platelet and low-dose warfarin therapy. A study of the natural history of IgANx revealed 2 courses, a slowly progressive course with end-stage renal failure (ESRF) at 7.7 years and a more rapid course at 3.3 years. Triple therapy (cyclophosphamide, persantin and low-dose warfarin) delayed progression to ESRF by about 8 years and for some patients up to 20 years. Documentation of abnormal suppressor T cell function provided the basis for immune therapy. Four patterns of proteinuria were present in IgANx and it is the quality and not so much the quantity of proteinuria which determined the prognosis. Low molecular weight proteinuria was a bad prognostic marker. A controlled therapeutic trial using ACEI/ATRA showed that therapy decreases proteinuria, improves renal function and converts non-selective to selective proteinuria. Subsequent work confirmed that it was the ATRA, not the ACEI which contributed to improved renal function. Individual anti proteinuria response to ATRA varies depending on ACE gene polymorphism. We found that the II genotype of the ACE gene was renoprotective and patients with this genotype had significantly reduced incidence of ESRF compared to those with the DD genotype. Patients responsive to ATRA therapy can retard progression to ESRF by up to 32 years. Mild renal failure can be reversed with possible regression of glomerulosclerosis because of glomerular remodelling by ATRA.
Disease Progression ; Evidence-Based Medicine ; history ; Genetic Predisposition to Disease ; Genomics ; history ; Glomerulonephritis, IGA ; genetics ; history ; History, 20th Century ; History, 21st Century ; Humans ; Polymorphism, Genetic ; Singapore

Background/Aims: Serum fibrosis scores comprised of common laboratory tests have high utility to assess severity of liver fibrosis. We aimed to derive and validate a hepatocellular carcinoma (HCC) risk score based on serum fibrosis scores to predict HCC in treatment-naïve chronic hepatitis B (CHB) patients. Methods: Fifteen thousand one hundred eighty-seven treatment-naïve adult CHB patients were identified to form the training cohort in this retrospective study. Individual fibrosis score was included to construct a new HCC prediction score. The score was externally validated in an independent treatment-naïve Korean CHB cohort. Results: 180/15,187 patients (1.2%) in training cohort and 47/4,286 patients (1.1%) in validation cohort developed HCC during a mean follow-up of 52 and 50 months, respectively. The newly developed HCC risk score, Liang score, is composed of gender, age, hepatitis B virus DNA, fibrosis-4 (FIB-4) index, and ranges from 0 to 22. Area under the time-dependent receiver operating characteristic curve of Liang score was 0.79 (95% confidence interval, 0.70–0.89). A cutoff value of nine provided an extremely high negative predictive value of 99.9% and high sensitivity of 90.0% at 5 years in the validation cohort. Patients with Liang score ≤9 had HCC incidence <0.2% per year in both training and validation cohorts, in whom HCC surveillance might be exempted. Conclusion A novel HCC risk score, Liang score, based on FIB-4 index, is applicable and accurate to identify treatment-naïve CHB patients with very low risk of HCC to be exempted from HCC surveillance.

Background/Aims: Serum fibrosis scores comprised of common laboratory tests have high utility to assess severity of liver fibrosis. We aimed to derive and validate a hepatocellular carcinoma (HCC) risk score based on serum fibrosis scores to predict HCC in treatment-naïve chronic hepatitis B (CHB) patients. Methods: Fifteen thousand one hundred eighty-seven treatment-naïve adult CHB patients were identified to form the training cohort in this retrospective study. Individual fibrosis score was included to construct a new HCC prediction score. The score was externally validated in an independent treatment-naïve Korean CHB cohort. Results: 180/15,187 patients (1.2%) in training cohort and 47/4,286 patients (1.1%) in validation cohort developed HCC during a mean follow-up of 52 and 50 months, respectively. The newly developed HCC risk score, Liang score, is composed of gender, age, hepatitis B virus DNA, fibrosis-4 (FIB-4) index, and ranges from 0 to 22. Area under the time-dependent receiver operating characteristic curve of Liang score was 0.79 (95% confidence interval, 0.70–0.89). A cutoff value of nine provided an extremely high negative predictive value of 99.9% and high sensitivity of 90.0% at 5 years in the validation cohort. Patients with Liang score ≤9 had HCC incidence <0.2% per year in both training and validation cohorts, in whom HCC surveillance might be exempted. Conclusion A novel HCC risk score, Liang score, based on FIB-4 index, is applicable and accurate to identify treatment-naïve CHB patients with very low risk of HCC to be exempted from HCC surveillance.

Background/Aims: We aimed to determine the association between blood urea level and incident cirrhosis, hepatic decompensation, and hepatocellular carcinoma in chronic liver disease (CLD) patients. Methods: The association between blood urea level and liver fibrosis/liver-related events were evaluated on continuous scale with restricted cubic spline curves based on generalized additive model or Cox proportional hazards models. Then, the above associations were evaluated by urea level within intervals. Results: Among 4,282 patients who had undergone liver stiffness measurement (LSM) by transient elastography, baseline urea level had a U-shaped association with LSM and hepatic decompensation development after a median follow-up of 5.5 years. Compared to patients with urea of 3.6–9.9 mmol/L, those with urea ≤3.5 mmol/L (adjusted hazard ratio [aHR], 4.15; 95% confidence interval [CI], 1.68–10.24) and ≥10 mmol/L (aHR, 5.22; 95% CI, 1.86–14.67) had higher risk of hepatic decompensation. Patients with urea ≤3.5 mmol/L also had higher risk of incident cirrhosis (aHR, 3.24; 95% CI, 1.50–6.98). The association between low urea level and incident cirrhosis and hepatic decompensation was consistently observed in subgroups by age, gender, albumin level, and comorbidities. The U-shaped relationship between urea level and LSM was validated in another population screening study (n=917). Likewise, urea ≤3.5 mmol/L was associated with a higher risk of incident cirrhosis in a territory-wide cohort of 12,476 patients with nonalcoholic fatty liver disease at a median follow-up of 9.9 years (aHR, 1.27; 95% CI, 1.03–1.57). Conclusions We identified a U-shaped relationship between the urea level and liver fibrosis/incident cirrhosis/hepatic decompensation in patients with CLD.

BACKGROUNDIn general vagus nerve stimulation (VNS) can serve as an adjunctive treatment for patients with refractory partial-onset seizures. And we evaluated the long-term efficacy and safety of VNS in a group of Chinese patients with refractory epilepsy.

METHODSOf 127 patients with refractory epilepsy, 13 patients who were not eligible for surgical intervention were implanted with the Cyberonics VNS system. Seizure frequency, physical examination and side effects profile were recorded at follow-up visits for a minimum of 18 months.

RESULTSMean duration of treatment was 47.4 months, and the longest follow-up period was 71 months. Mean baseline seizure frequency was 26.6 seizures per month. The mean percentage reductions in convulsions were 33.2%, 47.1% and 40.0% at 6, 12 and 18 months, respectively. One patient became seizure free, and six (46%) had 50% or more reduction in seizure frequency. Response was poor (< 20% reduction) in five patients (39%). Side effects were uncommon.

CONCLUSIONSThe effectiveness of VNS was sustained and was well tolerated but benefited only a sub-group of patients with intractable convulsions.

Adolescent ; Adult ; Electric Stimulation Therapy ; methods ; Epilepsy ; therapy ; Female ; Follow-Up Studies ; Humans ; Male ; Prospective Studies ; Prostheses and Implants ; Treatment Outcome ; Vagus Nerve ; physiology

BACKGROUNDObesity is now an epidemic in most parts of the world. In this cross sectional study, we report the most recent data on obesity in Hong Kong Chinese working population and compare the changes over 10 years.

METHODSBetween July 2000 and March 2002, 5882 adult subjects from the working class in Hong Kong were recruited (2716 men (46.2%) and 3166 women (53.8%)). They were randomly selected using computer generated codes according to the distribution of occupational groups. Results of this study were compared with the data collected from a prevalence survey for cardiovascular risk factors in a Hong Kong Chinese working population conducted in 1990 (1513 subjects, 910 men (60.1%) and 603 women (39.9%)).

RESULTSStandardized percentages of overweight, obesity, and central obesity, in Hong Kong Chinese working population were 59.7%, 35.0%, 26.7% in men and 32.0%, 21.7%, 26.7% in women. Compared to the data collected in 1990, the percentage of obesity increased by 5% in men and reduced by 6% in women. The percentage of central obesity doubled in men (from 12.2% to 26.7%) but remained stable in women.

CONCLUSIONSThere is a doubling of the percentage of central obesity in Hong Kong Chinese working men over previous decade. Education and proper lifestyle modification program to tackle this social health issue are urgently indicated.

Adolescent ; Adult ; Aged ; Female ; Hong Kong ; epidemiology ; Humans ; Male ; Middle Aged ; Obesity ; epidemiology ; Time Factors ; Work

Cytomegalovirus (CMV) is distinct among members of the Herpesviridae family for having the largest dsDNA genome (230 kb). Packaging of large dsDNA genome is known to give rise to a highly pressurized viral capsid, but molecular interactions conducive to the formation of CMV capsid resistant to pressurization have not been described. Here, we report a cryo electron microscopy (cryoEM) structure of the murine cytomegalovirus (MCMV) capsid at a 9.1 Å resolution and describe the molecular interactions among the ∼3000 protein molecules in the MCMV capsid at the secondary structure level. Secondary structural elements are resolved to provide landmarks for correlating with results from sequence-based prediction and for structure-based homology modeling. The major capsid protein (MCP) upper domain (MCPud) contains α-helices and β-sheets conserved with those in MCPud of herpes simplex virus type 1 (HSV-1), with the largest differences identified as a "saddle loop" region, located at the tip of MCPud and involved in interaction with the smallest capsid protein (SCP). Interactions among the bacteriophage HK97-like floor domain of MCP, the middle domain of MCP, the hook and clamp domains of the triplex proteins (hoop and clamp domains of TRI-1 and clamp domain of TRI-2) contribute to the formation of a mature capsid. These results offer a framework for understanding how cytomegalovirus uses various secondary structural elements of its capsid proteins to build a robust capsid for packaging its large dsDNA genome inside and for attaching unique functional tegument proteins outside.
Amino Acid Sequence ; Capsid Proteins ; chemistry ; metabolism ; ultrastructure ; Cryoelectron Microscopy ; Models, Molecular ; Molecular Sequence Data ; Muromegalovirus ; chemistry ; ultrastructure ; Protein Binding ; Protein Multimerization ; Protein Structure, Quaternary ; Protein Structure, Tertiary