Plasma DNA as a potential biomarker for breast cancer detection

Breast cancer is a major malignancy among Indonesian women. It is often diagnosed inthe later stages of cancer, which leads to poor prognosis and survival of the patients.This study investigated plasma DNA concentration as a potential biomarker for breastcancer. The benefit of using this detection is the cost-effectiveness and the samples canbe collected from patients using non-invasive methods. Plasma samples were obtainedfrom healthy controls (n=18) and cancer patients (n=22). Each sample was split intotwo equal portions for DNA isolation using two different methods for the NaI methodand a commercially available kit (Qiagen/ QA) method. The DNA concentration wasdetermined by using a GeneQuant spectrophotometer (Pharmacia). The t-test was usedfor statistical analysis, which was performed using the SPSS 17.0 software. Compared tothe commercial method, extraction using NaI yielded higher DNA concentration, both fromsamples of healthy controls and cancer patients (p=0,008 and p=0.000, respectively).Furthermore, regardless of the isolation method used, the plasma DNA concentrationwas higher in healthy controls than in cancer cases (p=0,032 and p=0.005, for NaIand QA methods, respectively). In conclusion, isolation methods significantly affect DNAconcentrations. The plasma DNA concentration of healthy controls is significantly higherthan those of the cancer cases, suggesting that plasma DNA concentration might be apotential biomarker for breast cancer detection with less invasive sampling method thantissue biopsies

The effect of continued folic acid supplementation beyond the first trimester on unmetabolised folic acid in late gestation

Folic acid (FA) is the synthetic form of the vitamin folate. Pregnant women are advised to take FA supplements before conception and during the first three months of pregnancy to reduce their chances of having a neural tube defect (NTDs) affected pregnancy, severe birth such as spina bifida and anencephaly. However, NTDs occur in the first month of pregnancy, and after that, there is no known benefit of continuing FA. Current recommendations do not advise stopping FA, so most women continue to take FA throughout pregnancy. Concerns have been raised that excess FA, especially in later pregnancy, may lead to adverse maternal and child health outcomes. These include large for gestational age, gestational diabetes, autism spectrum disorders, and childhood allergy. Australian Health authorities could simply change recommendations to advise women to women to stop FA once pregnancy is confirmed. Policymakers warn that changing recommendations will confuse women and undermine three decades of successful public health efforts encouraging women to take FA to reduce NTDs. All harms are based on observational evidence, which is insufficient to change policy. Only a high-quality RCT can supply definitive proof. Circulating unmetabolised folic acid (UMFA) in serum is used as a biomarker of excess FA intake and has been associated with an increased risk of adverse outcomes in some studies. Before commencing a large RCT, we first wanted to determine whether removing FA from prenatal supplements after the first trimester reduces the amount of UMFA at 36 weeks gestation. We conducted a two-arm, parallel, double-blind RCT to address this question. Women with a singleton pregnancy 12-16 weeks (n=103) gestation were randomly assigned to a multi-micronutrient supplement without (intervention) or with 800 μg folic acid/day (control, current standard practice) from enrolment until 36 weeks gestation. We chose 800 μg/d because it is Australia's most commonly used FA dose. Of the 103 women randomised, 90 finished the study. The primary outcome was the difference in maternal serum UMFA concentration between the groups at 36 weeks. Only 12% of women had UMFA above the limit of quantification (LOQ); thus, we could not compare UMFA concentration. However, fewer women in the no folic acid (intervention) compared to the 800 μg folic acid/day (control) group (72% [n=33/46] vs 98% [n=43/44]; p = 0.001) had UMFA above the LOD. Removing FA from multi-micronutrient prenatal supplements after 12 weeks gestation reduced the number of women with detectable UMFA at 36 weeks gestation. However, differences in UMFA concentration between treatment groups were not quantifiable. Whether continued FA use beyond the first trimester increases the risk of adverse maternal and child health outcomes remains unclear. This can only be answered with adequately powered RCTs to determine if removing folic acid from supplements after the first trimester alters the rate of outcomes. Only after this trial is complete can an informed decision be made about the risks of continued FA supplementation after the first trimester.Thesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 202

Sex differences in the association of vitamin D and metabolic risk factors with carotid intima-media thickness in obese adolescents

BACKGROUND: It has been shown that vitamin D is associated with obesity and the development of atherosclerosis. Less is known about this association among adolescents with obesity. OBJECTIVES: To determine the association of vitamin D level and metabolic risk factors with carotid intima-media thickness (CIMT) among obese adolescents. METHODS: We conducted a cross-sectional study among obese children aged 15 to 17 years in Yogyakarta, Indonesia. The association of vitamin D and other metabolic risk factors (triglyceride, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), and insulin resistance using homeostasis model assessment of insulin resistance (HOMA-IR)) with CIMT was explored by multivariable linear regression models. RESULTS: Out of 156 obese adolescents, 55.8% were boys. Compared to girls, boys had higher BMI z-score, waist circumference, and HDL-cholesterol. After adjustment for age, sex and second-hand smoke exposure, high HOMA-IR, total cholesterol, LDL-cholesterol and triglyceride levels were associated with higher odds of elevated CIMT. In analyses stratified by sex, a similar trend was observed in boys, while none of the risk factors were associated with CIMT in girls. We observed no association between vitamin D and CIMT. CONCLUSIONS: Hyperinsulinemia, higher total cholesterol and LDL cholesterol were associated with greater odds of elevated CIMT among obese adolescent boys

Ethnic-Specific Differences in Vitamin D Status Is Associated with Adiposity

BackgroundLow circulating 25 hydroxyvitamin D [25(OH)D] concentrations are common in obesity (BMI ≥30 kg/m2) and a negative relationship with body fat distribution has recently been reported. Ethnic-specific differences in body fat distribution have been described with South Asians are reported to have greater visceral adipose tissue (VAT), which could influence circulating 25(OH)D concentrations. The objective of this study is to investigate the relationship between plasma 25(OH)D, adiposity, and body fat distribution in Europeans and South Asians.Methods/Principal Findings187 Europeans and 192 South Asians were assessed for demographics, anthropometrics, and plasma 25(OH)D concentrations. Subcutaneous adipose tissue (SAT) and VAT were quantified by CT scan, and percent body fat by DEXA. Data were assessed by general linear models. South Asians had lower (P<0.001) plasma 25(OH)D concentrations and higher VAT (P = 0.04) than Europeans. Plasma 25(OH)D concentrations were negatively (P<0.05) associated with BMI, waist circumference, percent body fat, total adipose tissue, VAT, and SAT in unadjusted models and negatively (P<0.05) associated with VAT, SAT, and percent body fat after adjusting for BMI, ethnicity, age, and season of blood collection in males and females. When percent body fat, VAT, and SAT were included in the same model, only VAT remained negatively (P<0.05) associated with plasma 25(OH)D concentrations. Ethnicity remained significant in all models (P<0.001).ConclusionCompared to other adipose tissue compartments, VAT may have a distinct role in determining plasma 25(OH)D concentrations, which may account for the lower levels in South Asians

The Gene-Lifestyle Interaction on Leptin Sensitivity and Lipid Metabolism in Adults: A Population Based Study

Background: Obesity has been associated with leptin resistance and this might be caused by genetic factors. The aim of this study was to investigate the gene-lifestyle interaction betwee

Long-term exposure to PM2.5 and fasting plasma glucose in non-diabetic adolescents in Yogyakarta, Indonesia

Background: Indonesia is facing serious air pollution. However, very few studies have been conducted to examine the health risks of air pollution in Indonesia, particularly for adolescents. Objective: To assess the association between long-term exposure to ambient particles with a diameter of <2.5 mm (PM2.5) and fasting plasma glucose (FPG) in adolescents. Methods: A cross-sectional study was conducted in 482 adolescents aged 14e18 years in Yogyakarta, Indonesia in 2016. We finally included 469 (97.30%) participants who had no missing data for data analysis. We collected individual data on socio-demographics, behavioral habits, and health information through standardized questionnaires. Satellite-based PM2.5 concentrations from 2013 to 2016 were assigned based on participants’ residential addresses. The association between PM2.5 and FPG was examined using a generalized linear regression model while FPG was modeled as a continuous variable. An ordered logistic regression model was used to assess the relationship between PM2.5 and FPG categories. Results: Every 1 mg/m3 increase in PM2.5 was associated with a 0.34 mg/dL [95 confidence interval (95% CI): 0.08 mg/dL, 0.59 mg/dL] increase in FPG levels. Comparing with the low FPG level (under 86 mg/dL), every 1 mg/m3 increase in PM2.5 was associated with a 10.20% (95% CI: 1.60%, 19.80%) increase in the odds of impaired fasting glucose (IFG) (100e125 mg/dL). Stratified analyses indicated greater effects on participants with hypertension [odds ratio (OR) ¼ 1.30, 95% CI: 1.09, 1.57] and those had higher physical activities (OR ¼ 1.36, 95% CI: 1.09, 1.57). Adolescents’ sex, obesity status and different cutoff points of FPG did not modify the association between the exposure to PM2.5 and FPG levels. Conclusion: Long-term exposure to PM2.5 was associated with increased FPG levels in Indonesian nondiabetic adolescents.Wenhua Yu, Dian Caturini Sulistyoningrum, Danijela Gasevic, Rongbin Xu, Madarina Julia, Indah Kartika Murni, Zhuying Chen, Peng Lu, Yuming Guo, Shanshan L

The role of vitamin D and adiponectin in ethnic-specific differences in body fat distribution and risk for cardiovascular disease

Background: Body fat distribution, in particular visceral adipose tissue (VAT), contributes to risk of cardiovascular disease (CVD). The Multicultural-Community Health Assessment Trial (M-CHAT) reported that South Asians have greater VAT than Europeans despite similar BMIs, putting them at greater risk of CVD. However, the molecular mechanisms underlying ethnic-specific differences in body fat distribution are unclear. Low circulating 25-hydroxyvitamin D (25OHD) and adiponectin concentrations are prevalent in individuals with obesity (BMI ≥ 30kg/m²), and are associated with increased risk of CVD. Furthermore, 25OHD is inversely associated with blood pressure. Adiponectin is an adipokine that has insulin-sensitizing, anti-inflammatory, and anti-atherogenic properties. Adiponectin circulates as isoforms low (LMW), medium (MMW), and the reported most biologically active isoform, high (HMW) molecular weight. This thesis aims to investigate ethnic-specific differences in the relationship between plasma 25OHD and adiponectin concentrations with body fat distribution and CVD risk factors. Methods/Results: Europeans (n=171) and South Asians (n=176) from the M-CHAT cohort were assessed for demographics, plasma 25OHD, total and HMW adiponectin concentrations, and CVD risk factors. A computed tomography (CT) scan was used to quantify VAT and subcutaneous adipose tissue (SAT) deposition. South Asians had lower (p < 0.001) 25OHD in comparison to the Europeans (63.0 nmol/L vs. 39 nmol/L, respectively). VAT was inversely associated (p < 0.05) with 25OHD even after adjustment for age, sex, BMI, season of blood collection, SAT and total body fat (%). This suggests that VAT mediates the relationship between plasma 25OHD and CVD risk. Furthermore, the inverse association between systolic and diastolic blood pressure and 25OHD was no longer significant after adjustment for VAT. However, circulating plasma adiponectin concentrations remained strongly associated with fasting plasma HDL-cholesterol, triglycerides, insulin, and HOMA-insulin resistance (HOMA-IR), even after adjustment for VAT. Interestingly, South Asians also had lower (p<0.001) total and HMW adiponectin concentrations compared to Europeans. Conclusion: These findings demonstrate that plasma 25OHD and total and HMW adiponectin concentrations are associated with VAT deposition in Europeans and South Asians. Furthermore, plasma 25OHD and total and HMW adiponectin concentrations are lower in South Asians than the Europeans, which may contribute to elevated CVD risk in South Asians.Medicine, Faculty ofPathology and Laboratory Medicine, Department ofGraduat

Studi komparasi beberapa metode skrining penilaian status gizi pada pasien dewasa rawat inap rumah sakit

Background: It is necessary to diagnose level of malnutrition in hospitalized patient to give optimal nutrition support. Many different nutrition screening assessment have been developed. In Indonesia, Simple Nutrition Screening Tool (SNST) that had been used in same hospital and the result was good enough in validity-realibility. Objective: To assessed that SNST were simple and practical nutrition screening tool for detecting level of malnutrition in different type of hospitalized patient. Method: Observational cross-sectional design with total of sampling two hundred and eighty seven adult patients from 2nd and 3rd class of surgical, internal, or neurology ward of RSUD Sleman. Independent variables are SNST, Nutritional Risk Screening (NRS) 2002, Malnutrition Screening Tool (MST), and Malnutrition Universal Screening Tool (MUST). Dependent variables are Subjective Global Assessment (SGA), body mass index (BMI), mid upper arm circumference (MUAC), and hemoglobin (Hb). Receive Operating Curve (ROC) were used for measuring validity of each screening tools. The proportion difference between at-risk group and not at-risk group was assessed by Chi-square test. The mean difference of BMI, MUAC, and Hb between both of group was assessed by independent sample t-test. Results: SNST has highest validity compared to NRS-2002, MST, and MUST with Sensitivity 99,0%, Specificity 84,5 and Area Under Curve (AUC) 0,917. Based on SNST, the proportion difference of at-risk group and not at-risk group between surgical patients and internal-neurology patients was statistically significant (p<0,05); the proportion difference of at-risk group and not at-risk group between young adult, adult, and elderly patients was statistically significant (p<0,05); the mean difference of BMI, MUAC, and Hb between at-risk group and not at-risk group was also statistically significant (p<0,05). Conclusion: All of the nutrition screening tools can be used as predictor of malnutrition in hospitalized patients but, the SNST has the best validity as a nutrition screening to predict malnutrition

Studi komparasi beberapa metode skrining penilaian status gizi pada pasien dewasa rawat inap rumah sakit

Background: It is necessary to diagnose level of malnutrition in hospitalized patient to give optimal nutrition support. Many different nutrition screening assessment have been developed. In Indonesia, Simple Nutrition Screening Tool (SNST) that had been used in same hospital and the result was good enough in validity-realibility.Objective: To assessed that SNST were simple and practical nutrition screening tool for detecting level of malnutrition in different type of hospitalized patient.Method: Observational cross-sectional design with total of sampling two hundred and eighty seven adult patients from 2nd and 3rd class of surgical, internal, or neurology ward of RSUD Sleman. Independent variables are SNST, Nutritional Risk Screening (NRS) 2002, Malnutrition Screening Tool (MST), and Malnutrition Universal Screening Tool (MUST). Dependent variables are Subjective Global Assessment (SGA), body mass index (BMI), mid upper arm circumference (MUAC), and hemoglobin (Hb). Receive Operating Curve (ROC) were used for measuring validity of each screening tools. The proportion difference between at-risk group and not at-risk group was assessed by Chi-square test. The mean difference of BMI, MUAC, and Hb between both of group was assessed by independent sample t-test.Results: SNST has highest validity compared to NRS-2002, MST, and MUST with Sensitivity 99,0%, Specificity 84,5 and Area Under Curve (AUC) 0,917. Based on SNST, the proportion difference of at-risk group and not at-risk group between surgical patients and internal-neurology patients was statistically significant (p<0,05); the proportion difference of at-risk group and not at-risk group between young adult, adult, and elderly patients was statistically significant (p<0,05); the mean difference of BMI, MUAC, and Hb between at-risk group and not at-risk group was also statistically significant (p<0,05).Conclusion: All of the nutrition screening tools can be used as predictor of malnutrition in hospitalized patients but, the SNST has the best validity as a nutrition screening to predict malnutrition