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  1. Zulkipli MS, Rampal S, Bulgiba A, Peramalah D, Jamil N, See LLC, et al.
    Trans R Soc Trop Med Hyg, 2021 07 01;115(7):764-771.
    PMID: 33587144 DOI: 10.1093/trstmh/trab021
    BACKGROUND: Dengue, an acute infectious disease caused by a flavivirus, is a threat to global health. There is sparse evidence exploring obesity and the development of more severe dengue cases in adults. With increasing prevalence of obesity in areas with a high risk of dengue infection, obesity may increase the burden and mortality related to dengue infection. Our study aimed to determine the association between obesity and the development of more severe dengue infection in primary healthcare settings and whether these associations were modified by dengue fever phase.

    METHODS: A cohort study was conducted among laboratory-confirmed dengue patients aged >18 y in the central region of Peninsular Malaysia from May 2016 to November 2017. We collected demographic, clinical history, physical examination and laboratory examination information using a standardized form. Dengue severity (DS) was defined as either dengue with warning signs or severe dengue. Participants underwent daily follow-up, during which we recorded their vital signs, warning signs and full blood count results. Incidence of DS was modeled using mixed-effects logistic regression. Changes in platelet count and hematocrit were modeled using mixed-effects linear regression. The final multivariable models were adjusted for age, gender, ethnicity and previous dengue infection.

    RESULTS: A total of 173 patients were enrolled and followed up. The mean body mass index (BMI) was 37.4±13.75 kg/m2. The majority of patients were Malay (65.9%), followed by Chinese (17.3%), Indian (12.7%) and other ethnic groups (4.1%). A total of 90 patients (52.0%) were male while 36 patients (20.8%) had a previous history of dengue infection. BMI was significantly associated with DS (adjusted OR=1.17; 95% CI 1.04 to 1.34) and hematocrit (%) (aβ=0.09; 95% CI 0.01 to 0.16), but not with platelet count (x103/µL) (aβ=-0.01; 95% CI -0.84 to 0.81). In the dose response analysis, we found that as BMI increases, the odds of DS, hematocrit levels and platelet levels increase during the first phase of dengue fever.

    CONCLUSION: Higher BMI and higher hematocrit levels were associated with higher odds of DS. Among those with high BMI, the development of DS was observed during phase one of dengue fever instead of during phase two. These novel results could be used by clinicians to help them risk-stratify dengue patients for closer monitoring and subsequent prevention of severe dengue complications.

  2. Zulkipli MS, Dahlui M, Jamil N, Peramalah D, Wai HVC, Bulgiba A, et al.
    PLoS Negl Trop Dis, 2018 02;12(2):e0006263.
    PMID: 29415036 DOI: 10.1371/journal.pntd.0006263
    BACKGROUND: Severe dengue infection often has unpredictable clinical progressions and outcomes. Obesity may play a role in the deterioration of dengue infection due to stronger body immune responses. Several studies found that obese dengue patients have a more severe presentation with a poorer prognosis. However, the association was inconclusive due to the variation in the results of earlier studies. Therefore, we conducted a systematic review and meta-analysis to explore the relationship between obesity and dengue severity.

    METHODS: We performed a systematic search of relevant studies on Ovid (MEDLINE), EMBASE, the Cochrane Library, Web of Science, Scopus and grey literature databases. At least two authors independently conducted the literature search, selecting eligible studies, and extracting data. Meta-analysis using random-effects model was conducted to compute the pooled odds ratio with 95% confidence intervals (CI).

    FINDINGS: We obtained a total of 13,333 articles from the searches. For the final analysis, we included a total of fifteen studies among pediatric patients. Three cohort studies, two case-control studies, and one cross-sectional study found an association between obesity and dengue severity. In contrast, six cohort studies and three case-control studies found no significant relationship between obesity and dengue severity. Our meta-analysis revealed that there was 38 percent higher odds (Odds Ratio = 1.38; 95% CI:1.10, 1.73) of developing severe dengue infection among obese children compared to non-obese children. We found no heterogeneity found between studies. The differences in obesity classification, study quality, and study design do not modify the association between obesity and dengue severity.

    CONCLUSION: This review found that obesity is a risk factor for dengue severity among children. The result highlights and improves our understanding that obesity might influence the severity of dengue infection.

  3. Zhao D, Kim MH, Pastor-Barriuso R, Chang Y, Ryu S, Zhang Y, et al.
    PLoS One, 2016;11(1):e0146057.
    PMID: 26731527 DOI: 10.1371/journal.pone.0146057
    IMPORTANCE: Intraocular pressure (IOP) reduction or stabilization is the only proven method for glaucoma management. Identifying risk factors for IOP is crucial to understand the pathophysiology of glaucoma.

    OBJECTIVE: To examine the associations of change in body mass index (BMI), waist circumference, and percent fat mass with change in intraocular pressure (IOP) in a large sample of Korean adults.

    DESIGN, SETTING AND PARTICIPANTS: Cohort study of 274,064 young and middle age Korean adults with normal fundoscopic findings who attended annual or biennial health exams from January 1, 2002 to Feb 28, 2010 (577,981 screening visits).

    EXPOSURES: BMI, waist circumference, and percent fat mass.

    MAIN OUTCOME MEASURE(S): At each visit, IOP was measured in both eyes with automated noncontact tonometers.

    RESULTS: In multivariable-adjusted models, the average increase in IOP (95% confidence intervals) over time per interquartile increase in BMI (1.26 kg/m2), waist circumference (6.20 cm), and percent fat mass (3.40%) were 0.18 mmHg (0.17 to 0.19), 0.27 mmHg (0.26 to 0.29), and 0.10 mmHg (0.09 to 0.11), respectively (all P < 0.001). The association was stronger in men compared to women (P < 0.001) and it was only slightly attenuated after including diabetes and hypertension as potential mediators in the model.

    CONCLUSIONS AND RELEVANCE: Increases in adiposity were significantly associated with an increase in IOP in a large cohort of Korean adults attending health screening visits, an association that was stronger for central obesity. Further research is needed to understand better the underlying mechanisms of this association, and to establish the role of weight gain in increasing IOP and the risk of glaucoma and its complications.

  4. Zhao D, Kim MH, Pastor-Barriuso R, Chang Y, Ryu S, Zhang Y, et al.
    Invest Ophthalmol Vis Sci, 2014 Oct;55(10):6244-50.
    PMID: 25183763 DOI: 10.1167/iovs.14-14151
    To examine the longitudinal association between age and intraocular pressure (IOP) in a large sample of Korean men and women.
  5. Zhang Y, Chang Y, Ryu S, Cho J, Lee WY, Rhee EJ, et al.
    J Clin Endocrinol Metab, 2014 Jul;99(7):2467-76.
    PMID: 24708095 DOI: 10.1210/jc.2013-3832
    CONTEXT: Hyperthyroidism and hypothyroidism, both overt and subclinical, are associated with all-cause and cardiovascular mortality. The association between thyroid hormones and mortality in euthyroid individuals, however, is unclear.
    OBJECTIVE: To examine the prospective association between thyroid hormones levels within normal ranges and mortality endpoints.
    SETTING AND DESIGN: A prospective cohort study of 212 456 middle-aged South Korean men and women who had normal thyroid hormone levels and no history of thyroid disease at baseline from January 1, 2002 to December 31, 2009. Free T4 (FT4), free T3 (FT3), and TSH levels were measured by RIA. Vital status and cause of death ascertainment were based on linkage to the National Death Index death certificate records.
    RESULTS: After a median follow-up of 4.3 years, 730 participants died (335 deaths from cancer and 112 cardiovascular-related deaths). FT4 was inversely associated with all-cause mortality (HR = 0.77, 95% confidence interval 0.63-0.95, comparing the highest vs lowest quartile of FT4; P for linear trend = .01), and FT3 was inversely associated cancer mortality (HR = 0.62, 95% confidence interval 0.45-0.85; P for linear trend = .001). TSH was not associated with mortality endpoints.
    CONCLUSIONS: In a large cohort of euthyroid men and women, FT4 and FT3 levels within the normal range were inversely associated with the risk of all-cause mortality and cancer mortality, particularly liver cancer mortality.
  6. Zhang Y, Kim BK, Chang Y, Ryu S, Cho J, Lee WY, et al.
    Arterioscler Thromb Vasc Biol, 2014 Sep;34(9):2128-34.
    PMID: 25060795 DOI: 10.1161/ATVBAHA.114.303889
    OBJECTIVE: Overt and subclinical hypothyroidism are risk factors for atherosclerosis. It is unclear whether thyroid hormone levels within the normal range are also associated with atherosclerosis measured by coronary artery calcium (CAC).
    APPROACH AND RESULTS: We conducted a cross-sectional study of 41 403 apparently healthy young and middle-aged men and women with normal thyroid hormone levels. Free thyroxin, free triiodothyronine, and thyroid-stimulating hormone levels were measured by electrochemiluminescent immunoassay. CAC score was measured by multidetector computed tomography. The multivariable adjusted CAC ratios comparing the highest versus the lowest quartile of thyroid hormones were 0.74 (95% confidence interval, 0.60-0.91; P for trend <0.001) for free thyroxin, 0.81 (0.66-1.00; P for trend=0.05) for free triiodothyronine, and 0.78 (0.64-0.95; P for trend=0.01) for thyroid-stimulating hormone. Similarly, the odds ratios for detectable CAC (CAC >0) comparing the highest versus the lowest quartiles of thyroid hormones were 0.87 (0.79-0.96; P for linear trend <0.001) for free thyroxin, 0.90 (0.82-0.99; P for linear trend=0.02) for free triiodothyronine, and 0.91 (0.83-1.00; P for linear trend=0.03) for thyroid-stimulating hormone.
    CONCLUSIONS: In a large cohort of apparently healthy young and middle-aged euthyroid men and women, low-normal free thyroxin and thyroid-stimulating hormone were associated with a higher prevalence of subclinical coronary artery disease and with a greater degree of coronary calcification.
    KEYWORDS: thyroid hormones; thyrotropin; thyroxine; triiodothyronine
  7. Zain SM, Mohamed R, Cooper DN, Razali R, Rampal S, Mahadeva S, et al.
    PLoS One, 2014;9(4):e95604.
    PMID: 24743702 DOI: 10.1371/journal.pone.0095604
    Between 10 and 25% of individuals with non-alcoholic fatty liver disease (NAFLD) develop hepatic fibrosis leading to cirrhosis and hepatocellular carcinoma (HCC). To investigate the molecular basis of disease progression, we performed a genome-wide analysis of copy number variation (CNV) in a total of 49 patients with NAFLD [10 simple steatosis and 39 non-alcoholic steatohepatitis (NASH)] and 49 matched controls using high-density comparative genomic hybridization (CGH) microarrays. A total of 11 CNVs were found to be unique to individuals with simple steatosis, whilst 22 were common between simple steatosis and NASH, and 224 were unique to NASH. We postulated that these CNVs could be involved in the pathogenesis of NAFLD progression. After stringent filtering, we identified four rare and/or novel CNVs that may influence the pathogenesis of NASH. Two of these CNVs, located at 13q12.11 and 12q13.2 respectively, harbour the exportin 4 (XPO4) and phosphodiesterase 1B (PDE1B) genes which are already known to be involved in the etiology of liver cirrhosis and HCC. Cross-comparison of the genes located at these four CNV loci with genes already known to be associated with NAFLD yielded a set of genes associated with shared biological processes including cell death, the key process involved in 'second hit' hepatic injury. To our knowledge, this pilot study is the first to provide CNV information of potential relevance to the NAFLD spectrum. These data could prove invaluable in predicting patients at risk of developing NAFLD and more importantly, those who will subsequently progress to NASH.
  8. Zain SM, Mohamed Z, Mahadeva S, Rampal S, Basu RC, Cheah PL, et al.
    PLoS One, 2013;8(3):e58538.
    PMID: 23484035 DOI: 10.1371/journal.pone.0058538
    Angiotensin II type 1 receptor (AGTR1) has been reported to play a fibrogenic role in non-alcoholic fatty liver disease (NAFLD). In this study, five variants of the AGTR1 gene (rs3772622, rs3772627, rs3772630, rs3772633, and rs2276736) were examined for their association with susceptibility to NAFLD. Subjects made up of 144 biopsy-proven NAFLD patients and 198 controls were genotyped using TaqMan assays. The liver biopsy specimens were histologically graded and scored according to the method of Brunt. Single locus analysis in pooled subjects revealed no association between each of the five variants with susceptibility to NAFLD. In the Indian ethnic group, the rs2276736, rs3772630 and rs3772627 appear to be protective against NAFLD (p = 0.010, p = 0.016 and p = 0.026, respectively). Haplotype ACGCA is shown to be protective against NAFLD for the Indian ethnic subgroup (p = 0.03). Gene-gene interaction between the AGTR1 gene and the patatin-like phospholipase domain-containing 3 (PNPLA3) gene, which we previously reported as associated with NAFLD in this sample, showed a strong interaction between AGTR1 (rs3772627), AGTRI (rs3772630) and PNPLA3 (rs738409) polymorphisms on NAFLD susceptibility (p = 0.007). Further analysis of the NAFLD patients revealed that the G allele of the AGTR1 rs3772622 is associated with increased fibrosis score (p = 0.003). This is the first study that replicates an association between AGTR1 polymorphism and NAFLD, with further details in histological features of NAFLD. There is lack of evidence to suggest an association between any of the five variants of the AGTR1 gene and NAFLD in the Malays and Chinese. In the Indians, the rs2276736, rs3772630 and rs3772627 appear to protect against NAFLD. We report novel findings of an association between the G allele of the rs3772622 with occurrence of fibrosis and of the gene-gene interaction between AGTR1gene and the much-studied PNPLA3 gene.
  9. Zain SM, Mohamed Z, Mahadeva S, Cheah PL, Rampal S, Chin KF, et al.
    J Gastroenterol Hepatol, 2013 May;28(5):873-9.
    PMID: 23278404 DOI: 10.1111/jgh.12104
    Genetic polymorphism has been implicated as a factor for the occurrence of non-alcoholic fatty liver disease (NAFLD). This study attempted to assess whether polymorphisms in the leptin receptor (LEPR) gene and its combined effect with patatin-like phospholipase domain-containing protein 3 (PNPLA3/adiponutrin) are associated with risk of NAFLD.
  10. Zain SM, Mohamed R, Mahadeva S, Cheah PL, Rampal S, Basu RC, et al.
    Hum Genet, 2012 Jul;131(7):1145-52.
    PMID: 22258181 DOI: 10.1007/s00439-012-1141-y
    The adiponutrin (PNPLA3) rs738409 polymorphism has been found to be associated with susceptibility to non-alcoholic fatty liver disease (NAFLD) in various cohorts. We further investigated the association of this polymorphism with non-alcoholic steatohepatitis (NASH) severity and with histological features of NAFLD. A total of 144 biopsy-proven NAFLD patients and 198 controls were genotyped for PNPLA3 gene polymorphism (rs738409 C>G). The biopsy specimens were histologically graded by a qualified pathologist. We observed an association of G allele with susceptibility to NAFLD in the pooled subjects (OR 2.34, 95% CI 1.69-3.24, p < 0.0001), and following stratification, in each of the three ethnic subgroups, namely Chinese, Indian and Malay (OR 1.94, 95% CI 1.12-3.37, p = 0.018; OR 3.51, 95% CI 1.69-7.26, p = 0.001 and OR 2.05, 95% CI 1.25-3.35, p = 0.005, respectively). The G allele is associated with susceptibility to NASH (OR 2.64, 95% CI 1.85-3.75, p < 0.0001), with NASH severity (OR 1.85, 95% CI 1.05-3.26, p = 0.035) and with presence of fibrosis (OR 1.95, 95% CI 1.17-3.26, p = 0.013) but not with simple steatosis nor with other histological parameters. Although the serum triglyceride level is significantly higher in NAFLD patients compared to controls, the G allele is associated with decreased level of triglycerides (p = 0.029) in the NAFLD patients. Overall, the rs738409 G allele is associated with severity of NASH and occurrence of fibrosis in patients with NAFLD.
  11. Yun KE, Chang Y, Rampal S, Zhang Y, Cho J, Jung HS, et al.
    J Clin Gastroenterol, 2018 07;52(6):508-514.
    PMID: 28471937 DOI: 10.1097/MCG.0000000000000824
    GOALS: Because of shared risk factors between clinically manifest cardiovascular disease and colorectal cancer, we hypothesized the coexistence of subclinical atherosclerosis measured by coronary artery calcium (CAC) and colorectal adenoma (CRA) and that these 2 processes would also share common risk factors.

    BACKGROUND: No study has directly compared the risk factors associated with subclinical coronary atherosclerosis and CRA.

    STUDY: This was a cross-sectional study using multinomial logistic regression analysis of 4859 adults who participated in a health screening examination (2010 to 2011; analysis 2014 to 2015). CAC scores were categorized as 0, 1 to 100, or >100. Colonoscopy results were categorized as absent, low-risk, or high-risk CRA.

    RESULTS: The prevalence of CAC>0, CAC 1 to 100 and >100 was 13.0%, 11.0%, and 2.0%, respectively. The prevalence of any CRA, low-risk CRA, and high-risk CRA was 15.1%, 13.0%, and 2.1%, respectively. The adjusted odds ratios (95% confidence interval) for CAC>0 comparing participants with low-risk and high-risk CRA with those without any CRA were 1.35 (1.06-1.71) and 2.09 (1.29-3.39), respectively. Similarly, the adjusted odds ratios (95% confidence interval) for any CRA comparing participants with CAC 1 to 100 and CAC>100 with those with no CAC were 1.26 (1.00-1.6) and 2.07 (1.31-3.26), respectively. Age, smoking, diabetes, and family history of CRC were significantly associated with both conditions.

    CONCLUSIONS: We observed a graded association between CAC and CRA in apparently healthy individuals. The coexistence of both conditions further emphasizes the need for more evidence of comprehensive approaches to screening and the need to consider the impact of the high risk of coexisting disease in individuals with CAC or CRA, instead of piecemeal approaches restricted to the detection of each disease independently.

  12. Yip CH, Taib NA, Choo WY, Rampal S, Thong MK, Teo SH
    World J Surg, 2009 Oct;33(10):2077-81.
    PMID: 19649760 DOI: 10.1007/s00268-009-0146-8
    Mutations in BRCA1 and BRCA2 confer an increased risk to breast and other cancers, but to date there have only been limited numbers of studies of BRCA1- and BRCA2-associated cancers among Asians. Malaysia is a multiracial country with three main races: Malays, Chinese, Indians. We determined whether tumor pathologic features and clinical features differ in patients with and without BRCA mutations in this Asian population.
  13. Yang MH, Rampal S, Sung J, Choi YH, Son HJ, Lee JH, et al.
    Cancer Epidemiol Biomarkers Prev, 2014 Mar;23(3):499-507.
    PMID: 24443404 DOI: 10.1158/1055-9965.EPI-13-0682
    Colorectal cancer incidence is rapidly rising in many Asian countries, with rates approaching those of Western countries. This study aimed to evaluate the prevalence and trends of colorectal adenomas by age, sex, and risk strata in asymptomatic Koreans.
  14. Wan KS, Tok PSK, Yoga Ratnam KK, Aziz N, Isahak M, Ahmad Zaki R, et al.
    PLoS One, 2021;16(4):e0249394.
    PMID: 33852588 DOI: 10.1371/journal.pone.0249394
    INTRODUCTION: The reporting of Coronavirus Disease 19 (COVID-19) mortality among healthcare workers highlights their vulnerability in managing the COVID-19 pandemic. Some low- and middle-income countries have highlighted the challenges with COVID-19 testing, such as inadequate capacity, untrained laboratory personnel, and inadequate funding. This article describes the components and implementation of a healthcare worker surveillance programme in a designated COVID-19 teaching hospital in Malaysia. In addition, the distribution and characteristics of healthcare workers placed under surveillance are described.

    MATERIAL AND METHODS: A COVID-19 healthcare worker surveillance programme was implemented in University Malaya Medical Centre. The programme involved four teams: contact tracing, risk assessment, surveillance and outbreak investigation. Daily symptom surveillance was conducted over fourteen days for healthcare workers who were assessed to have low-, moderate- and high-risk of contracting COVID-19. A cross-sectional analysis was conducted for data collected over 24 weeks, from the 6th of March 2020 to the 20th of August 2020.

    RESULTS: A total of 1,174 healthcare workers were placed under surveillance. The majority were females (71.6%), aged between 25 and 34 years old (64.7%), were nursing staff (46.9%) and had no comorbidities (88.8%). A total of 70.9% were categorised as low-risk, 25.7% were moderate-risk, and 3.4% were at high risk of contracting COVID-19. One-third (35.2%) were symptomatic, with the sore throat (23.6%), cough (19.8%) and fever (5.0%) being the most commonly reported symptoms. A total of 17 healthcare workers tested positive for COVID-19, with a prevalence of 0.3% among all the healthcare workers. Risk category and presence of symptoms were associated with a positive COVID-19 test (p<0.001). Fever (p<0.001), cough (p = 0.003), shortness of breath (p = 0.015) and sore throat (p = 0.002) were associated with case positivity.

    CONCLUSION: COVID-19 symptom surveillance and risk-based assessment have merits to be included in a healthcare worker surveillance programme to safeguard the health of the workforce.

  15. Thergarajan G, Kumar S, Bhassu S, Omar SFBS, Rampal S
    PLoS One, 2019;14(3):e0211034.
    PMID: 30893309 DOI: 10.1371/journal.pone.0211034
    Increasing incidences of dengue have become a global health threat with major clinical manifestation including high fever and gastrointestinal symptoms. These symptoms were also expressed among Blastocystis sp. infected individuals, a parasite commonly seen in human stools. This parasite has been previously reported to replicate faster upon exposure to high temperature. The present study is a hospitalized-based cross-sectional study involved the collection of faecal sample from dengue patients. Stool examination was done by in vitro cultivation to isolate Blastocystis sp. Growth pattern of all the positive isolates were analyzed to identify the multiplication rate of Blastocystis sp. isolated from dengue patients. Distribution of Blastocystis sp. among dengue patients was 23.6%. Dengue patients who were positive for Blastocystis sp. infection denoted a significantly higher fever rate reaching 38.73°C (p<0.05) compared to the non-Blastocystis sp. infected patients (38.44°C). It was also found that Blastocystis sp. infected patients complained of frequenting the toilet more than five times a day (p<0.05) compared to those who were non-Blastocystis sp. infected. At the same time, the duration of hospitalization was significantly longer (p<0.05) for Blastocystis sp. infected dengue patients compared to the non-Blastocystis sp. infected patients. Besides, Blastocystis sp. isolated from dengue patients (in vivo thermal stress) showed a higher growth rate compared to the non-dengue isolated which was exposed to high temperature (in vitro thermal stress). Our findings suggest that presence of Blastocystis sp. during dengue infection could trigger the increase of temperature which could be due to highly elevated pro inflammatory cytokines by both parasitic and virus infection. This could justify why the temperature in Blastocystis sp. infected dengue patients is higher compared to the non-Blastocystis sp. infected patients. Higher temperature could have triggered a greater parasite multiplication rate that contributed to the aggravation of the gastrointestinal symptoms.
  16. Thanapal MR, Tata MD, Tan AJ, Subramaniam T, Tong JM, Palayan K, et al.
    ANZ J Surg, 2014 Jan-Feb;84(1-2):47-51.
    PMID: 23057502 DOI: 10.1111/j.1445-2197.2012.06210.x
    Although laparoscopic surgeries are associated with reduced surgical stress response and shortened post-operative recovery, intense pain and high analgesia requirements in the immediate post-operative period are often the chief complaints.
  17. Teh SW, Koh AE, Tong JB, Wu X, Samrot AV, Rampal S, et al.
    Front Cell Dev Biol, 2021;9:634131.
    PMID: 34490233 DOI: 10.3389/fcell.2021.634131
    Bone fractures have a high degree of severity. This is usually a result of the physical trauma of diseases that affect bone tissues, such as osteoporosis. Due to its highly vascular nature, the bone is in a constant state of remodeling. Although those of younger ages possess bones with high regenerative potential, the impact of a disrupted vasculature can severely affect the recovery process and cause osteonecrosis. This is commonly seen in the neck of femur, scaphoid, and talus bone. In recent years, mesenchymal stem cell (MSC) therapy has been used to aid in the regeneration of afflicted bone. However, the cut-off in blood supply due to bone fractures can lead to hypoxia-induced changes in engrafted MSCs. Researchers have designed several oxygen-generating biomaterials and yielded varying degrees of success in enhancing tissue salvage and preserving cellular metabolism under ischemia. These can be utilized to further improve stem cell therapy for bone repair. In this review, we touch on the pathophysiology of these bone fractures and review the application of oxygen-generating biomaterials to further enhance MSC-mediated repair of fractures in the three aforementioned parts of the bone.
  18. Teh SW, Elderdery A, Rampal S, Subbiah SK, Mok PL
    Contemp Oncol (Pozn), 2023;27(4):255-262.
    PMID: 38405210 DOI: 10.5114/wo.2023.135364
    INTRODUCTION: Cutaneous squamous cell carcinoma (SCC) is the second most common form of skin malignancy, representing around 20% of all skin cancers. It is the main cause of death due to non-melanoma skin cancer every year. Metastatic cutaneous SCC is associated with poor prognosis in patients and warrants a more effective and specific approach such as disruption of genes associated with cancer metastasis.

    MATERIAL AND METHODS: Matrix metalloproteinases (MMPs) are enzymes involved in cancer progression and are regarded as major oncotargets. Among others, MMP9 plays critical roles in tumour progression, angiogenesis, and invasion of cutaneous SCC. We aimed to determine whether the MMP9 gene is a suitable gene target for anti-cancer therapy for cutaneous SCC. We performed clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 transfection of guide RNA (gRNA) targeting the MMP9 gene into human cutaneous SCC cell line A431.

    RESULTS: Following CRISPR transfection treatment, the viability (p < 0.01) and migratory activities (p < 0.0001) of in vitro cutaneous SCC cells were found to be reduced significantly. The use of quantitative polymerase chain reaction (qPCR) also revealed downregulation of the mRNA expression levels of cancer-promoting genes TGF-β, FGF, PI3K, VEGF-A, and vimentin. Direct inhibition of the MMP9 gene was shown to decrease survivability and metastasis of cutaneous SCC cell line A431.

    CONCLUSIONS: Our findings provided direct evidence that MMP9 is important in the viability, proliferation, and metastasis of cutaneous SCC cells. It serves as a positive foundation for future CRISPR-based targeted anti-cancer therapies in treating skin cancer and other forms of malignancies that involve MMPs as the key determinants.

  19. Teh CH, Rampal S, Lim KH, Azahadi O, Tahir A
    Nicotine Tob Res, 2023 Jun 09;25(7):1340-1347.
    PMID: 36879440 DOI: 10.1093/ntr/ntad035
    INTRODUCTION: Tobacco use is one of the major preventable risk factors for premature death and disability worldwide. Understanding the trend of tobacco use over time is important for informed policy making.

    AIMS AND METHODS: The present study aimed to examine the changes in mean daily cigarette consumption among random samples of the Malaysian current smoker population over 20 years using an age-period-cohort (APC) approach. We conducted APC analysis using a multilevel hierarchical age-period-cohort model and data from four nationally representative, repeated cross-sectional surveys (National Health and Morbidity Survey) conducted in 1996, 2006, 2011, and 2015 among individuals aged 18 to 80 years. Analyses were also stratified by gender and ethnicity.

    RESULTS: Overall, mean daily cigarette consumption (smoking intensity) among current smokers increased with age until 60, after which a drop was observed. There were increases in daily cigarette consumption across birth cohorts. Age and cohort trends did not vary by gender but by ethnicity. The decreasing cigarette consumption after age 60 among the current smoker population was consistent with those observed among the Chinese and Indians, a trend that was not observed in Malays and other aborigines. In contrast, the increasing cohort trend was consistent with those observed among the Malays and other bumiputras.

    CONCLUSIONS: The present study highlighted important ethnic-specific trends for mean daily cigarette consumption among the current smoker population in Malaysia. These findings are essential in guiding the formulation of interventional strategies or implementation of national tobacco control policies and help achieve the Ministry of Health Malaysia's 2025 and 2045 targets for smoking prevalence.

    IMPLICATIONS: This is the first APC study on smoking intensity among current smokers in a multiracial, middle-income nation. Very few studies had performed gender- and ethnic-stratified APC analyses. The ethnic-stratified APC analyses provide useful insights into the overall age and cohort trends observed among the current smoker population in Malaysia. Therefore, the present study could add evidence to the existing literature on the APC trends of smoking intensity. The APC trends are also important in guiding the government to develop, implement, and evaluate antismoking strategies.

  20. Teh CH, Rampal S, Kee CC, Azahadi O, Tahir A
    Int J Obes (Lond), 2023 Dec;47(12):1302-1308.
    PMID: 37833560 DOI: 10.1038/s41366-023-01391-5
    OBJECTIVE: The global obesity epidemic remains a significant threat to public health and the economy. Age-period-cohort (APC) analysis is one method to model the trajectory of obesity. However, there is scarce published evidence of such analyses among the South East Asian population. This study aims to explore the sex and ethnic variations of BMI and waist circumference trajectories over time among non-institutionalized Malaysian adults aged 18 to 80 years.

    METHODS: Data from four population-based National Health and Morbidity Surveys conducted in 1996, 2006, 2010, and 2015 were pooled. Hierarchical Age-Period-Cohort (HAPC) analysis explored the trajectories of BMI and waist circumference across the life course and birth cohorts by sex and ethnicity. These models assumed no period effect.

    RESULTS: Generally, BMI and waist circumference trajectories increased across age and birth cohorts. These trajectories varied by sex and ethnicity. Females have more profound increasing BMI and waist circumference trajectories than their male counterparts as they age and as cohort recency increases. Chinese have less profound BMI and waist circumference increases across the life course and birth cohorts than other ethnic groups.

    CONCLUSIONS: The profound increasing cohort trajectories of obesity, regardless of sex and ethnicity, are alarming. Future studies should focus on identifying factors associated with the less profound cohort effect among the Chinese to reduce the magnitude of trajectories in obesity, particularly among future generations.

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