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Background and Purpose: Apolipoprotein E4 (APOE4) is a major genetic risk factor for Alzheimer's disease. However, the effect of APOE4 status on myelin remains unclear. This study investigated the effect of APOE4 on myelin content in cognitively impaired individuals using T2* gradient echo (GRE)-based myelin water fraction (MWF) imaging., Methods: Between August 2017 and January 2019, we evaluated 39 cognitively impaired patients (median age, 75 years; male:female = 8:31; Alzheimer's disease: mild cognitive impairment = 11:28). We obtained brain MWF values from white matter hyperintensities (WMHs) and normal-appearing white matter (NAWM). Linear regression analysis was performed to investigate the relationship between the APOE4 status and MWF and cognitive function and MWF., Results: Among the 39 cognitively impaired patients, nine (23.1%) were APOE4 carriers and 30 (76.9%) were noncarriers. APOE4 carriers had a lower hippocampal volume than noncarriers (p = .045), but other brain volume parameters were not differed. After age adjustment, the APOE4 status was significantly associated with reduced MWF in NAWM (β = -0.310 per allele; p = .049) but not in WMH (β = -0.258 per allele; p = .113). After age adjustment, MWF in NAWM was significantly associated with Mini-Mental State Examination score (β = 0.313, p = .031)., Conclusions: T2* GRE-based MWF imaging can reveal myelin loss, particularly in NAWM, in cognitively impaired patients among APOE4 carriers. In vivo MWF in NAWM might be a novel imaging marker of Alzheimer's disease, for clarifying the interactions between the white matter and cognitive dysfunction with respect to the APOE4 status., (© 2021 American Society of Neuroimaging.)

Antrodia cinnamomea is a well-known medicinal mushroom in Taiwan that exhibits anti-inflammatory biological activities. In rheumatoid arthritis (RA), chronic inflammation and angiogenesis driven by proinflammatory cytokines reflect the severity of the disease. Although biological treatments have improved the outlook for RA, no healing exists. Moreover, the available pharmacotherapies do not work for all patients and drug safety is a major consideration. Investigations into plant-based medicines hope to reveal better, more tolerable agents. We examined whether Antcin K, a phytosterol isolated from A. cinnamomea, has anti-angiogenic activity in RA. The GSE12021 gene dataset from the Gene Expression Omnibus (GEO) database was examined for levels of vascular endothelial growth factor (VEGF) expression in 10 RA and 10 osteoarthritis (OA) synovial tissue samples. In clinical samples, VEGF expression was analyzed by immunohistochemical staining and ELISA in normal and RA synovial tissue, as well as OA and RA synovial fluid. Collagen-induced arthritis (CIA) and control tissue was stained with hematoxylin and eosin (H&E) for histological changes; Safranin O/Fast Green staining examined histopathological changes and evidence of bone erosion. Human RA synovial fibroblasts (RASFs) were incubated with Antcin K and cell viability was examined by the MTT assay. VEGF mRNA expression was detected in RASFs using qPCR. Antcin K significantly inhibited VEGF expression and ameliorates endothelial progenitor cell (EPC) migration and tube formation in RASFs by downregulating the phospholipase C-γ/protein kinase C-α pathway. Antcin K also induced anti-angiogenic effects in human RASFs without cytotoxicity. PRACTICAL APPLICATIONS: Analysis of GEO dataset samples and human synovial fluids or synovial tissues revealed higher VEGF levels in rheumatoid arthritis (RA) samples compared with osteoarthritis (OA) and healthy control samples. VEGF levels were also higher in mice with collagen-induced arthritis (CIA) than in healthy controls. Antcin K markedly suppressed VEGF expression in human RA synovial fibroblasts and inhibited the migration and tube formation of epithelial progenitor cells (EPCs) by downregulating the phospholipase C-γ/protein kinase C-α pathway. Further investigations are warranted to examine the effects of Antcin K in other angiogenesis-associated disorders., (© 2021 Wiley Periodicals LLC.)

Background: Osteoarthritis (OA) is the most common joint disease, especially affecting the knee joint. Etoricoxib, a highly selective cyclooxygenase (COX)-2 inhibitor which can reduce postoperative pain after orthopaedic surgery. The aim of this study was to investigate the effects of oral etoricoxib on the development of OA and to examine concomitant changes in the nociceptive behaviour of rats., Method: OA was induced in wistar rats by anterior cruciate ligament transection (ACLT) of the right knee. The ACLT + etoricoxib groups received 6.7 or 33.3 mg/kg of oral etoricoxib three times a week for 12 consecutive weeks, starting at week 8 after ACLT. Nociceptive behaviours and changes in knee joint width during OA development were analyzed. Histopathological studies were then performed on the cartilage. Immunohistochemical analysis was performed to examine the effect of etoricoxib on the expression of transforming growth factor-beta (TGF-β) and nerve growth factor (NGF) in articular cartilage chondrocytes., Results: OA rats receiving etoricoxib showed a significantly lower degree of cartilage degeneration than the rats receiving placebo. Nociceptive behaviour studies showed significant improvement in the ACLT + etoricoxib groups compared to that in the ACLT group. Moreover, etoricoxib attenuated NGF expression, but increased TGF-β expression, in OA-affected cartilage., Conclusions: Oral etoricoxib in a rat OA model (a) attenuates the development of OA, (b) concomitantly reduces nociception, and (c) modulates chondrocyte metabolism, possibly by inhibiting NGF expression and increasing TGF-β expression., Significance: Oral administration of etoricoxib can attenuate the development of OA, with an associated attenuation of nociceptive behaviour in an experimental rat OA model. Moreover, etoricoxib attenuated NGF expression, but enhanced TGF-β expression in OA-affected chondrocytes. These findings may pave the way for further investigations of etoricoxib as a potential therapeutic target for the treatment of the inflammatory component in OA., (© 2019 European Pain Federation - EFIC®.)

Blast-induced traumatic brain injury has been on the rise in recent years because of the increasing use of improvised explosive devices in conflict zones. Our study investigates the response of a helmeted human head subjected to a blast of 1 atm peak overpressure, for cases with and without a standard polycarbonate (PC) face shield and for face shields comprising of composite PC and aerogel materials and with lateral edge extension. The novel introduction of aerogel into the laminate face shield is explored and its wave-structure interaction mechanics and performance in blast mitigation is analysed. Our numerical results show that the face shield prevented direct exposure of the blast wave to the face and help delays the transmission of the blast to reduce the intracranial pressures (ICPs) at the parietal lobe. However, the blast wave can diffract and enter the midface region at the bottom and side edges of the face shield, resulting in traumatic brain injury. This suggests that the bottom and sides of the face shield are important regions to focus on to reduce wave ingress. The laminated PC/aerogel/PC face shield yielded higher peak positive and negative ICPs at the frontal lobe, than the original PC one. For the occipital and temporal brain regions, the laminated face shield performed better than the original. The composite face shield with extended edges reduced ICP at the temporal lobe but increases ICP significantly at the parietal lobe, which suggests that a greater coverage may not lead to better mitigating effects., (Copyright © 2017 John Wiley & Sons, Ltd.)

Head injuries due to complex blasts are not well examined because of limited published articles on the subject. Previous studies have analyzed head injuries due to impact from a single planar blast wave. Complex or concomitant blasts refer to impacts usually caused by more than a single blast source, whereby the blast waves may impact the head simultaneously or consecutively, depending on the locations and distances of the blast sources from the subject, their blast intensities, the sequence of detonations, as well as the effect of blast wave reflections from rigid walls. It is expected that such scenarios will result in more serious head injuries as compared to impact from a single blast wave due to the larger effective duration of the blast. In this paper, the utilization of a head-helmet model for blast impact analyses in Abaqus(TM) (Dassault Systemes, Singapore) is demonstrated. The model is validated against studies published in the literature. Results show that the skull is capable of transmitting the blast impact to cause high intracranial pressures (ICPs). In addition, the pressure wave from a frontal blast may enter through the sides of the helmet and wrap around the head to result in a second impact at the rear. This study recommended better protection at the sides and rear of the helmet through the use of foam pads so as to reduce wave entry into the helmet. The consecutive frontal blasts scenario resulted in higher ICPs compared with impact from a single frontal blast. This implied that blast impingement from an immediate subsequent pressure wave would increase severity of brain injury. For the unhelmeted head case, a peak ICP of 330 kPa is registered at the parietal lobe which exceeds the 235 kPa threshold for serious head injuries. The concurrent front and side blasts scenario yielded lower ICPs and skull stresses than the consecutive frontal blasts case. It is also revealed that the additional side blast would only significantly affect ICPs at the temporal and parietal lobes when compared with results from the single frontal blast case. By analyzing the pressure wave flow surrounding the head and correlating them with the consequential evolution of ICP and skull stress, the paper provides insights into the interaction mechanics between the concomitant blast waves and the biological head model., (Copyright © 2014 John Wiley & Sons, Ltd.)

Background and Purpose: Products of Maillard reactions between aminoacids and reducing sugars are known to have anti-inflammatory properties. Here we have assessed the anti-arthritis effects of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal and its possible mechanisms of action., Experimental Approach: We used cultures of LPS-activated macrophages (RAW264.7 cells) and human synoviocytes from patients with rheumatoid arthritis for in vitro assays and the collagen-induced arthritis model in mice. NO generation, iNOS and COX2 expression, and NF-κB/IKK and STAT3 activities were measured in vitro and in joint tissues of arthritic mice, along with clinical scores and histopathological assessments. Binding of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal to STAT3 was evaluated by a pull-down assay and its binding site was predicted using molecular docking studies with Autodock VINA., Key Results: (E)-2,4-bis(p-hydroxyphenyl)-2-butenal (2.5-10 μg·mL(-1) ) inhibited LPS-inducedNO generation, iNOS and COX2 expression, and NF-κB/IKK and STAT3 activities in macrophage and human synoviocytes. This compound also suppressedcollagen-induced arthritic responses in mice by inhibiting expression of iNOS and COX2, and NF-κB/IKK and STAT3 activities; it also reduced bone destruction and fibrosis in joint tissues. A pull-down assay showed that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal interfered with binding of ATP to STAT3. Docking studies suggested that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal bound to the DNA-binding interface of STAT3 possibly inhibiting ATP binding to STAT3 in an allosteric manner., Conclusions and Implications: (E)-2,4-bis(p-hydroxyphenyl)-2-butenal exerted anti-inflammatory and anti-arthritic effects through inhibition of the NF-κB/STAT3 pathway by direct binding to STAT3. This compound could be a useful agent for the treatment of arthritic disease., (© 2014 The British Pharmacological Society.)

Head injury, being one of the main causes of death or permanent disability, continues to remain a major health problem with significant socioeconomic costs. Numerical simulations using the FEM offer a cost-effective method and alternative to experimental methods in the biomechanical studies of head injury. The present study aimed to develop two realistic subject-specific FEMs of the human head with detailed anatomical features from medical images (Model 1: without soft tissue and Model 2: with soft tissue and differentiation of white and gray matters) and to validate them against the intracranial pressure (ICP) and relative intracranial motion data of the three cadaver experimental tests. In general, both the simulated results were in reasonably good agreement with the experimental measured ICP and relative displacements, despite slight discrepancy in a few neutral density targets markers. Sensitivity analysis showed some variations in the brain's relative motion to the material properties or marker's location. The addition of soft tissue in Model 2 helped to damp out the oscillations of the model response. It was also found that, despite the fundamental anatomical differences between the two models, there existed little evident differences in the predicted ICP and relative displacements of the two models. This indicated that the advancements on the details of the extracranial features would not improve the model's predicting capabilities of brain injury., (Copyright © 2013 John Wiley & Sons, Ltd.)

Fractional flow reserve (FFR) is the gold standard to guide coronary interventions. However it can only be obtained via invasive angiography. The objective of this study is to propose a noninvasive method to determine FFRCT by combining computed tomography angiographic (CTA) images and computational fluid dynamics (CFD) technique. Utilizing the method, this study explored the effects of diameter stenosis (DS), stenosis length, and location on FFRCT. The baseline left anterior descending (LAD) model was reconstructed from CTA of a healthy porcine heart. A series of models were created by adding an idealized stenosis (with DS from 45% to 75%, stenosis length from 4 mm to 16 mm, and at 4 locations separately). Through numerical simulations, it was found that FFRCT decreased (from 0.89 to 0.74), when DS increased (from 45% to 75%). Similarly, FFRCT decreased with the increase of stenosis length and the stenosis located at proximal position had lower FFRCT than that at distal position. These findings are consistent with clinical observations. Applying the same method on two patients' CTA images yielded FFRCT close to the FFR values obtained via invasive angiography. The proposed noninvasive computation of FFRCT is promising for clinical diagnosis of CAD.

This study is aimed at developing a high quality, validated finite element (FE) human head model for traumatic brain injuries (TBI) prediction and prevention during vehicle collisions. The geometry of the FE model was based on computed tomography (CT) and magnetic resonance imaging (MRI) scans of a volunteer close to the anthropometry of a 50th percentile male. The material and structural properties were selected based on a synthesis of current knowledge of the constitutive models for each tissue. The cerebrospinal fluid (CSF) was simulated explicitly as a hydrostatic fluid by using a surface-based fluid modeling method. The model was validated in the loading condition observed in frontal impact vehicle collision. These validations include the intracranial pressure (ICP), brain motion, impact force and intracranial acceleration response, maximum von Mises stress in the brain, and maximum principal stress in the skull. Overall results obtained in the validation indicated improved biofidelity relative to previous FE models, and the change in the maximum von Mises in the brain is mainly caused by the improvement of the CSF simulation. The model may be used for improving the current injury criteria of the brain and anthropometric test devices.

Background: Incense use is an integral part of daily life in large parts of Asia. The burning of incense is a powerful producer of particulate matter and the smoke contains a multitude of well-characterized carcinogens. However, to the authors' knowledge, no convincing association has been reported between exposure to incense smoke and the development of cancer. Therefore, the relation between incense use and the risk of respiratory tract carcinomas was analyzed in a prospective cohort study., Methods: Between 1993 and 1998, a population-based cohort of 61,320 Singapore Chinese who were free of cancer and ages 45 to 74 years completed a comprehensive interview regarding living conditions and dietary and lifestyle factors. Through linkage to population-based registries, the cohort was followed through 2005 and cancer occurrence determined. The relative risk for these cancers associated with incense use was estimated using a Cox proportional hazards model., Results: A total of 325 upper respiratory tract (UPT) carcinomas and 821 lung carcinomas were observed during follow-up. Incense use was associated with a significantly increased risk of UPT carcinomas other than nasopharyngeal, whereas no overall effect was observed on lung cancer. The duration and intensity of incense use were associated with an increased risk of squamous cell carcinomas in the entire respiratory tract (P for trend = .004), whereas there was no significant association noted between incense use and nonsquamous cell carcinomas. The relative risk of squamous cell carcinomas among long-term incense users was 1.8 (95% confidence interval [95% CI], 1.2-2.6; P = .004) in the entire respiratory tract., Conclusions: The results of the current study indicate that long-term use of incense is associated with an increased risk of squamous cell carcinoma of the respiratory tract.

We have previously demonstrated that baculovirus can efficiently transduce human mesenchymal stem cells (MSCs) and MSCs-derived adipogenic, chondrogenic, and osteogenic progenitors without compromising the differentiation capacity. Remarkably, the transgene expression level and duration varied widely with the differentiation states at which the progenitors were transduced. However, whether the variation was a general phenomenon and what caused the variation were unclear. Here we demonstrated that transduction of the MSCs and MSC-derived progenitors using baculoviruses carrying egfp driven by CMV, EF-1alpha or CAG promoter resulted in a general trend of varied expression, that is, the chondrogenic progenitors allowed for the poorest expression while the adipogenic progenitors conferred the best expression. Quantification of the nuclear and cytoplasmic egfp gene copy numbers by quantitative real-time PCR revealed that the varied expression did not arise from the discrepancies in gene delivery efficiency nor was it due to the disparities in nuclear transport efficiency. In contrast, the transcription levels paralleled the overall expression levels. These data suggested that although the egfp genes could be efficiently delivered into the nuclei of chondrogenic progenitors, they were not transcribed as well as they were in the adipogenic progenitors. In conclusion, the rapidly altering cellular transcription machinery in the course of differentiation progression predominantly led to the varied expression levels.

Background: Nasopharyngeal carcinoma (NPC) is a rare disease in most populations; however, in areas of Southeast Asia and North Africa and in the Arctic, undifferentiated NPC is the most frequent pharyngeal malignancy. Although smoking and alcohol have been established firmly as synergistic risk factors for other pharyngeal carcinomas, previous studies on the association between these risk factors and NPC have not been consistent. Therefore, the authors analyzed this relation in a cohort of Singapore Chinese, which is a population with a high incidence of NPC., Methods: From 1993 to 1998, a population-based cohort of 61,320 Singapore Chinese ages 45 years to 74 years who were free of cancer completed a comprehensive interview on living conditions and dietary and lifestyle factors. By linkage to Singapore population-based registries, the cohort was followed through 2005, and cancer occurrence was determined. The relative risk of NPC and other oropharyngeal carcinomas in the cohort was investigated by using a Cox proportional hazards model., Results: In total, 173 NPCs and 75 other oropharyngeal carcinomas were observed during 601,879 person-years of follow-up. Smoking for >40 years was associated with a doubled risk of NPC (relative risk, 2.0; 95% confidence interval, 1.2-3.3), whereas smoking intensity, age at smoking initiation, and alcohol consumption were not associated with NPC risk. In contrast, smoking duration, smoking intensity, age at smoking initiation, and alcohol consumption all were associated with an increased risk of other oropharyngeal carcinoma (P for trend, <.0001)., Conclusions: Smoking and alcohol influenced the risk of NPC and other oropharyngeal carcinomas differently in a high-incidence NPC population. Long-term smoking was a risk factor for NPC, but alcohol consumption was not.

Background: The purpose of this study was to determine the ovarian findings on integrated positron emission tomography/computed tomography scans during follow-up in cervical cancer patients with ovarian transposition., Method: We retrospectively reviewed the clinical data and integrated 18F-fluorodeoxyglucose positron emission tomography/computed tomography of women with ovarian transposition during radical hysterectomy for cervical cancer between December 2003 and March 2006., Results: Eighty-four premenopausal women had ovarian transposition performed during the study period. Twelve positron emission tomography/computed tomography scans from 11 patients were registered for the current study and three women were diagnosed with metastasis: two in lung and one in pelvis. Two patients complained of menopausal symptoms during follow-up, and the hormonal tests were consistent with it. In the current study, an integrated positron emission tomography/computed tomography scan detected one patient with right lower abdominal mass with increased 18F-fluorodeoxyglucose uptake, which was identified as a transposed right ovary. Clinical information of ovarian transposition was helpful in interpretation of the lesion. In the patient, transposed ovary was associated with increased fluorodeoxyglucose uptake, with standard uptake values ranging from 3.7 to 5.5. Other positron emission tomography/computed tomography scans did not show abnormal uptake of 18F-fluorodeoxyglucose., Conclusions: Transposed ovary in premenopausal women may appear on integrated positron emission tomography/computed tomography scan as a mass with increased 18F-fluorodeoxyglucose uptake, which may be associated with preserved ovarian function. Clinical information regarding transposition should be noted in order not to interpret these as recurrent or metastatic lesions.

Baculovirus has emerged as a promising vector for in vivo or ex vivo gene therapy. To date, the infectious titer and multiplicity of infection (MOI) based on the ability of baculovirus to infect insect cells are commonly adopted to indicate the virus dosage. However, the infectious titer and MOI do not reliably represent the baculovirus transducing ability, making the comparison of baculovirus-mediated gene transfer difficult. To determine the baculovirus transducing ability more rapidly and reliably, we developed a protocol to evaluate the transducing titers of baculovirus stocks. The virus was diluted twofold serially and used to transduce HeLa cells. The resultant transduction efficiencies were measured by flow cytometry for the calculation of transducing titers. Compared to the infectious titer, the determination of transducing titer is more reproducible as the standard deviations among measurements are smaller. Also, the transducing titers can be obtained in 24 h, which is significantly faster as opposed to 4-7 days to obtain the infectious titer. More importantly, we demonstrated that baculoviruses with higher transducing titers could transduce cells at higher efficiency and yield stronger and longer transgene expression, confirming that the transducing titer was representative of the baculovirus transducing ability. This finding is particularly significant for ex vivo gene delivery whereby unconcentrated viruses are used for transduction and long-term transgene expression is desired. In this regard, our titration protocol provides a simple, fast, and reliable measure to evaluate the quality of virus stocks during virus production and purification, and is helpful to predict the performance of vector supernatants and ensure reproducible gene delivery experiments., (Copyright 2005 Wiley Periodicals, Inc.)

Background: The purpose of this study was to evaluate the predictive value of preoperative serum CA-125 levels in the assessment of disease extent and clinical outcome of endometrial cancer., Method: This retrospective study evaluated 92 women with pathologically proven endometrial carcinoma scheduled for treatment that had preoperative serum CA-125 levels between January 1999 and February 2006. The association of preoperative serum CA-125 with a variety of histopathologic factors was evaluated. Statistical analysis was performed using chi2/Fisher's exact test and a logistic regression. Survival was studied with the Kaplan-Meier method and Cox regression models., Results: Elevated serum CA-125 levels were significantly correlated with advanced-stage disease (p<0.001), lymph node metastases (p<0.001), increased depth of myometrial invasion (p=0.001), and positive peritoneal cytology (p=0.026). Multivariate analyses using logistic regression showed that lymph node metastases had the most significant effect on the elevation of preoperative serum CA-125 levels (p=0.004). Patients with a serum CA-125 < or =28.5 U/ml had a significantly better five-year disease-free survival than those with an elevated level in this study: 85.6% versus 60.0% (p=0.004)., Conclusions: The preoperative serum CA-125 level appears to be a significant independent predictor of lymph node metastasis and prognosis after surgical intervention. Therefore, preoperative serum CA-125 may be a useful tool, in the clinical setting, for optimal individualized patient management.

Background: Recent epidemiologic studies have suggested that the anatomic distribution of colorectal carcinoma may have undergone a distal to proximal shift over several decades, which has been attributed variously to environmental and genetic factors as well as preventive intervention., Methods: Trends in subsite distribution and the incidence rate of colorectal carcinoma among Chinese in Singapore between 1968 and 1992 were explored using data from the Singapore Cancer Registry (n = 10,489). Age-standardized incidence rates were computed and compared further using age-period-cohort models by subsite and gender., Results: The proportion of lesions in the distal colon was found to have increased from 23.2% to 24.4% whereas that for the proximal colon and rectum were fairly consistent over the past 25 years. Our results also showed that age-standardized rates have doubled in proximal lesions (2-3% annually) and more than doubled in distal lesions (3-4% annually) whereas rates in rectal carcinoma have shown a slight increase or stability over time. The patterns of change in all subsite tumors could be attributed to a significant birth cohort effect., Conclusions: The results of the current study suggest that incidence rates have increased rapidly with no distal to proximal shift observed among ethnic Chinese in Singapore over the past 25 years. The pattern of change differs from findings reported in high incidence countries such as the U. S. and parts of Europe, suggesting that the preventive intervention and early diagnostic capabilities that may have played an important role in these countries have had less effect in Asia. The rapid overall increase in the incidence rate of colon carcinoma supports the role of dietary and other environmental factors as possible risk factors.

Background: Non-Hodgkin's lymphoma has increased in incidence in many countries, particularly in the West. Advances in diagnostic methods and the understanding of the disease over time pose a challenge to the interpretation of these trends. The aim of this study was to determine if the disease has increased in Singapore, a newly industrialized Asian country, and to examine the possible factors that may account for any observed changes., Methods: Data from the population-based Singapore Cancer Registry for the period 1968 to 1992 were reviewed to determine time trends based on sex and ethnic group. The Poisson regression model was fitted to the cross-tabulated data to obtain the adjusted incidence density ratios., Results: A total of 1988 cases of non-Hodgkin's lymphoma were included in the analysis. There was an overall increase in incidence among both Chinese and Malaysians. However, the rate of increase was greater in females (age-standardized rate from 1.8 per 100,000 in 1968-1972 to 4.5 per 100,000 in 1988-1992) than in males (3.2 per 100,000 to 5.9 per 100,000 in the same time periods). Between ethnic groups, Malay females were at higher overall risk compared with their Chinese counterparts (incidence density ratio 1.32; 95% confidence interval, 1.08-1.61). Although a substantial proportion of patients diagnosed with Hodgkin's disease between 1968 and 1972 were reclassified on review, using present criteria, as having non-Hodgkin's lymphoma, it is unlikely that this, and other recent changes in histologic interpretation, could have accounted for an increase of this magnitude., Conclusions: Non-Hodgkin's lymphoma has increased in incidence among the Chinese and Malay populations in Singapore. The pattern of increase differs from that of the common cancer sites, and suggests the need to look for environmental and genetic factors that have not yet been elucidated.