Predictors and Trends of Diabetic Ketoacidosis at Diagnosis of Type 1 Diabetes Mellitus in Malaysian Children.

Objectives: Previous reports indicate that diabetic ketoacidosis (pDKA) rates in Malaysian children with type 1 diabetes range between 54-75%, which is higher than most European nations. Knowledge of trends and predictors of DKA can be helpful to inform measures to lower the rates of DKA. However, this data is lacking in Malaysian children. Hence, the aim of this study was to determine the predictors and trends of pDKA in Malaysian children at the initial diagnosis of T1DM. Methods: This cross-sectional study examined demographic, clinical and biochemical data of all newly diagnosed Malaysian children aged 0-18 years with T1DM over 11 years from a single centre. Regression analyses determined the predictors and trends. Results: The overall pDKA rate was 73.2%, of which 54.9% were severe DKA. Age ≥5 years (OR 12.29, 95% CI 1.58, 95.58, p= 0.017) and misdiagnosis (OR 3.73, 95% CI 1.36, 10.24 p=0.01) were significant predictors of a DKA presentation. No significant trends in the annual rates of DKA, severe DKA nor children <5 years presenting with DKA were found over the 11-years study period. Conclusion: DKA rates at initial diagnosis of T1DM in Malaysian children are high and severe DKA accounts for a significant burden. Though misdiagnosis and age ≥5 years are predictors of DKA, misdiagnosis can be improved through awareness and education. The lack of downward trends in DKA and severe DKA highlights the urgency to develop measures to curb its rates.

Depression mediates the relationship between alexithymia and obesity in the Northern Finland Birth Cohort 1966 (NFBC1966).

BACKGROUND: The fact that a complex relationship exists between alexithymia and body mass index (BMI) is well established, but the underlying mechanisms remain poorly understood. Here, we explore the relationship between alexithymia and depressive symptoms in relation to adiposity measures, including the direct and indirect effect of alexithymia and depressive symptoms on obesity over a 15-year time-period, in the Northern Finland Birth Cohort 1966 (NFBC1966). METHODS: The study included individuals from the Northern Finland Birth Cohort 1966 (NFBC1966) who had available data for adiposity measures (body mass index and waist-to-hip ratio), alexithymia (measured by the 20-Item Toronto Alexithymia Scale: TAS-20), depressive symptoms (measured by the 13-item depression subscale of Hopkins Symptom Checklist: HSCL-13) at age of 31 years (n = 4773) and 46 years (n = 4431). Pearson's (r) correlation, and multiple linear regression were used to investigate the relationships between alexithymia, depressive symptoms, and adiposity measures. The potential mediating role of depressive symptoms was examined via Hayes' procedure (PROCESS). RESULTS: Positive correlations were confirmed between adiposity measures (BMI and WHR) and the TAS-20 score (and its subscale), but not between obesity and HSCL-13 score. The strongest correlation was between the DIF (difficulty identifying feelings) subscale of the TAS-20 and HSCL-13 at both time points (31 y: r(3013) = 0.41, p < 0.01, 46 y: r(3013) = 0.43, p < 0.01). Depressive symptoms completely (z = 2.55 (±0.00003), p = 0.01) and partly (z = 2.16 (±0.0001), p = 0.03) mediated the alexithymia-obesity relationship over the 15-year time-period. LIMITATIONS: Other psychological and environmental factors such as interoception, dietary intake and physical activities may also play a role as a potential mediating factor in alexithymia-obesity relationship. CONCLUSIONS: Our findings provide additional insights of theoretical framework of depressive symptoms mediation effect in the relationship between alexithymia and obesity. Alexithymia and depression should, therefore, be considered in the design of future clinical obesity research.

Personality Traits and Sociodemographic Factors Associated with the Use of E-Cigarettes, Waterpipe and Conventional Cigarettes among Medical University Students.

This study aimed to investigate the prevalence and sociodemographic characteristics of smokers in a private medical university in Malaysia and to examine whether there is an association between personality traits and various smoking types. There were 468 participants in this study and the mean age was 20.97 years (±2.743). The prevalence of conventical cigarette users, e-cigarette users, and water pipe users was 4.7%, 6.4%, and 4.0%, respectively. Parents' annual income (p = 0.001) and ethnicity (p < 0.001) were significantly associated with the current smoker group. Binary logistic regression modelling revealed that study participants with either Malay (OR 4.23, 95% CI 1.73, 10.34) or Chinese (OR 4.16, 95% CI 1.98, 8.73) ethnicity were approximately four times more likely to use tobacco products compared with study participants with Indian and Other ethnicities. Lower parents' annual income was almost four times more likely to be associated with smoking behaviour (OR 3.82, 95% CI 1.58, 9.27). Significant differences in mean personality traits score of Openness (p = 0.018) and Extraversion (p = 0.004) were observed between never-smoker and current smoker study participants. In addition, cigarette users scored higher in Conscientiousness personality traits compared with non-cigarette whereas e-cigarette users and waterpipe users scored lower in Extraversion (p = 0.02). Post-hoc analysis revealed that the never-smoker group scored higher in Extraversion compared with the dual tobacco user group (p = 0.03). In addition, the single tobacco user group scored higher in Agreeableness personality trait compared with the never-smoker group (p = 0.01). Deeper understanding of the different cognitive dimensions, ethnicities, and educational backgrounds can potentially impact smoking prevention and cessation programs.

Personality Traits and Annual Income Determine the Willingness to Pay for a Single Tooth Implant.

The objective of this study was to evaluate the factors influencing the willingness to pay for a single tooth implant in Malaysia and to assess if an additional evidence-based patient education video increases the willingness to pay. A total of 100 subjects seeking single tooth replacement at the Oral Health Centre, International Medical University (IMU), Kuala Lumpur, Malaysia, were asked to complete questionnaires about personal demographics and personality traits. Subsequently, they were randomly allocated into two groups. Group C received a conventional patient-dentist interaction on treatment options for missing teeth, while Group EV received the same content with an additional evidence-based video on the survival rate and complications for each option from recent meta-analyses. Willingness to pay the median price and the highest price that the subjects were willing to pay were assessed by a structured bidding process. A higher annual income was significantly associated with willingness to pay the median price for a single tooth implant (χ2 = 6.91, p = 0.03). Dominant personality traits of openness (r = -0.25), conscientiousness (r = -0.30) and agreeableness (r = -0.20) were negatively correlated with the highest price that the patients were willing to pay for a single tooth implant (Pearson's correlation test, p < 0.05). No significant difference in willingness to pay was found between Group C and Group EV (χ2 = 0.05, p > 0.05). In conclusion, patient education strategies for single tooth replacements with dental implants should be customized based on a patient's personality and income to maximize effectiveness.

COVID-19 Sample Pooling: From RNA Extraction to Quantitative Real-time RT-PCR.

The COVID-19 pandemic requires mass screening to identify those infected for isolation and quarantine. Individually screening large populations for the novel pathogen, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is costly and requires a lot of resources. Sample pooling methods improve the efficiency of mass screening and consume less reagents by increasing the capacity of testing and reducing the number of experiments performed, and are therefore especially suitable for under-developed countries with limited resources. Here, we propose a simple, reliable pooling strategy for COVID-19 testing using clinical nasopharyngeal (NP) and/or oropharyngeal (OP) swabs. The strategy includes the pooling of 10 NP/OP swabs for extraction and subsequent testing via quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR), and may also be applied to the screening of other pathogens.

A novel strategy for community screening of SARS-CoV-2 (COVID-19): Sample pooling method.

The rapid global spread of the coronavirus disease (COVID-19) has inflicted significant health and socioeconomic burden on affected countries. As positive cases continued to rise in Malaysia, public health laboratories experienced an overwhelming demand for COVID-19 screening. The confirmation of positive cases of COVID-19 has solely been based on the detection of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) using real-time reverse transcription polymerase chain reaction (qRT-PCR). In efforts to increase the cost-effectiveness and efficiency of COVID-19 screening, we evaluated the feasibility of pooling clinical Nasopharyngeal/Oropharyngeal (NP/OP) swab specimens during nucleic acid extraction without a reduction in sensitivity of qRT-PCR. Pools of 10 specimens were extracted and subsequently tested by qRT-PCR according to the WHO-Charité protocol. We demonstrated that the sample pooling method showed no loss of sensitivity. The effectiveness of the pooled testing strategy was evaluated on both retrospective and prospective samples, and the results showed a similar detection sensitivity compared to testing individual sample alone. This study demonstrates the feasibility of using a pooled testing strategy to increase testing capacity and conserve resources, especially when there is a high demand for disease testing.

Relationship between BMI and emotion-handling capacity in an adult Finnish population: The Northern Finland Birth Cohort 1966.

BACKGROUND: Alexithymia, a difficulty in identifying and expressing emotions, has been associated with obesity and eating disorders in small-scale cross-sectional studies. Here, we assess the relationship between body mass index (BMI) and alexithymia in a large cohort of free-living Finnish adults over a 15-year period. METHODS: Participants were drawn from the Northern Finnish Birth Cohort 1966 (NFBC1966). The 20-Item Toronto Alexithymia Scale (TAS-20) was used as a measure of alexithymia and was completed at the age of 31 years (31y: n = 4841), and 46 years (46y: n = 5404). BMI was recorded at both time points. Where data at both time points were available (n = 3274), the relationship between changes in BMI and TAS-20 over this time period was also investigated. RESULTS: BMI was significantly and positively associated with TAS-20 score (p<0.0001, both at 31 years and at 46 years of ages). The association remained statistically significant after adjustment for potential confounders (sex, marital status and several socio-economic indicators). In individuals who experienced the greatest change in BMI (in either direction) over the 15-year period, there was a modest mean increase in TAS-20 score. CONCLUSIONS: Our data revealed that TAS-20 score was correlated with and co-varied with body mass status. We suggest that future clinical research should consider the role of alexithymia in obesity. Further investigation of this relationship is warranted to ensure that the needs of obese subjects with undiagnosed alexithymia are considered in the design of weight management programmes.

Genetic polymorphisms associated with breast cancer in malaysian cohort.

Genome-wide association studies have discovered multiple single nucleotide polymorphisms (SNPs) associated with the risk of common diseases. The objective of this study was to demonstrate the replication of previously published SNPs that showed statistical significance for breast cancer in the Malaysian population. In this case-control study, 80 subjects for each group were recruited from various hospitals in Malaysia. A total of 768 SNPs were genotyped and analyzed to distinguish risk and protective alleles. A total of three SNPs were found to be associated with increased risk of breast cancer while six SNPs showed protective effect. All nine were statistically significant SNPs (p ≤ 0.01), five SNPs from previous studies were successfully replicated in our study. Significant modifiable (diet) and non-modifiable (family history of breast cancer in first degree relative) risk factors were also observed. We identified nine SNPs from this study to be either conferring susceptibility or protection to breast cancer which may serve as potential markers in risk prediction.

Role of genetic & environment risk factors in the aetiology of colorectal cancer in Malaysia.

BACKGROUND & OBJECTIVES: Colorectal cancer (CRC) is second only to breast cancer as the leading cause of cancer-related deaths in Malaysia. In the Asia-Pacific area, it is the highest emerging gastrointestinal cancer. The aim of this study was to identify single nucleotide polymorphisms (SNPs) and environmental factors associated with CRC risk in Malaysia from a panel of cancer associated SNPs. METHODS: In this case-control study, 160 Malaysian subjects were recruited, including both with CRC and controls. A total of 768 SNPs were genotyped and analyzed to distinguish risk and protective alleles. Genotyping was carried out using Illumina's BeadArray platform. Information on blood group, occupation, medical history, family history of cancer, intake of red meat and vegetables, exposure to radiation, smoking and drinking habits, etc was collected. Odds ratio (OR), 95% confidence interval (CI) were calculated. RESULTS: A panel of 23 SNPs significantly associated with colorectal cancer risk was identified (P<0.01). Of these, 12 SNPs increased the risk of CRC and 11 reduced the risk. Among the environmental risk factors investigated, high intake of red meat (more than 50% daily proportion) was found to be significantly associated with increased risk of CRC (OR=6.52, 95% CI :1.93-2.04, P=0.003). Two SNPs including rs2069521 and rs10046 in genes of cytochrome P450 (CYP) superfamily were found significantly associated with CRC risk. For gene-environment analysis, the A allele of rs2069521 showed a significant association with CRC risk when stratified by red meat intake. INTERPRETATION & CONCLUSIONS: In this preliminary study, a panel of SNPs found to be significantly associated with CRC in Malaysian population, was identified. Also, red meat consumption and lack of physical exercise were risk factors for CRC, while consumption of fruits and vegetables served as protective factor.

Association of genetic and non-genetic risk factors with the development of prostate cancer in Malaysian men.

There is growing global interest to stratify men into different levels of risk to developing prostate cancer, thus it is important to identify common genetic variants that confer the risk. Although many studies have identified more than a dozen common genetic variants which are highly associated with prostate cancer, none have been done in Malaysian population. To determine the association of such variants in Malaysian men with prostate cancer, we evaluated a panel of 768 SNPs found previously associated with various cancers which also included the prostate specific SNPs in a population based case control study (51 case subjects with prostate cancer and 51 control subjects) in Malaysian men of Malay, Chinese and Indian ethnicity. We identified 21 SNPs significantly associated with prostate cancer. Among these, 12 SNPs were strongly associated with increased risk of prostate cancer while remaining nine SNPs were associated with reduced risk. However, data analysis based on ethnic stratification led to only five SNPs in Malays and 3 SNPs in Chinese which remained significant. This could be due to small sample size in each ethnic group. Significant non-genetic risk factors were also identified for their association with prostate cancer. Our study is the first to investigate the involvement of multiple variants towards susceptibility for PC in Malaysian men using genotyping approach. Identified SNPs and non-genetic risk factors have a significant association with prostate cancer.

Influences of multiple genetic polymorphisms on ovarian cancer risk in Malaysia.

OBJECTIVE: The identification of high-risk individuals can help to improve early cancer detection and patient survival. Risk assessment, however, can only be accomplished if the risk factors are known. To date, the genetic risk factors for ovarian cancer, other than mutations in the BRCA1/2 genes, have never been systematically explored in Malaysia. The present study aims to identify from a panel of cancer-associated single-nucleotide polymorphisms (SNPs), those associated with ovarian cancer risk in Malaysia. METHODS: A total of 768 SNPs associated with various cancers among Asians were identified through a search of the relevant literature, and these SNPs were then screened for their association with ovarian cancer. A total of 160 Malaysian subjects were recruited for the study, including both ovarian cancer patients and controls. Genotyping was carried out using Illumina BeadArray platform. RESULTS: A panel of 45 SNPs that are significantly (p<0.05) associated with ovarian cancer risk was identified. These ovarian cancer-associated SNPs were located in genes implicated in various pathways of carcinogenesis. Of these 45 SNPs, 5 have been previously associated with either ovarian cancer risk or survival. CONCLUSION: This study has identified a panel of 45 SNPs that are significantly associated with ovarian cancer in a Malaysian population.

Identification of genetic and non-genetic risk factors for nasopharyngeal carcinoma in a Southeast Asian population.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is endemic in Southern Chinese and Southeast Asian populations. Geographical and ethnic clustering of the cancer is due to genetic, environmental, and lifestyle risk factors. This case-control study aimed to identify or confirm both genetic and non-genetic risk factors for NPC in one of the endemic countries, Malaysia. MATERIALS AND METHOD: A panel of 768 single-nucleotide polymorphisms (SNPs) previously associated with various cancers and known non-genetic risk factors for NPC were selected and analyzed for their associations with NPC in a case-control study. RESULTS: Statistical analysis identified 40 SNPs associated with NPC risk in our population, including 5 documented previously by genome-wide association studies (GWAS) and other case-control studies; the associations of the remaining 35 SNPs with NPC were novel. In addition, consistent with previous studies, exposure to occupational hazards, overconsumption of salt-cured foods, red meat, as well as low intake of fruits and vegetables were also associated with NPC risk. CONCLUSIONS: In short, this study confirmed and/or identified genetic, environmental and dietary risk factors associated with NPC susceptibility in a Southeast Asian population.

Laser capture microdissection with genome-wide expression profiling displayed gene expression signatures in endometrioid endometrial cancer.

This research determined genes contributing to the pathogenesis of endometrioid endometrial cancer (EEC). Eight pairs of microdissected EEC samples matched with normal glandular epithelium were analyzed using microarray. Unsupervised analysis identified 162 transcripts (58 up- and 104 down-regulated) that were differentially expressed (p < .01, fold change ≥ 1.5) between both groups. Quantitative real-time polymerase chain reaction (qPCR) validated the genes of interest: SLC7A5, SATB1, H19, and ZAK (p < .05). Pathway analysis revealed genes involved in acid amino transport, translation, and chromatin remodeling (p < .05). Laser capture microdissection (LCM) followed by microarray enabled precise assessment of homogeneous cell population and identified putative genes for endometrial carcinogenesis.