Association of TP53 Codon 72 Arg>Pro Polymorphism with Breast and Lung Cancer Risk in the South Asian Population: A Meta-Analysis

Background: A transversion missense polymorphism of the TP53 tumor suppressor gene at the codon 72 codes proline instead of arginine causes an altered p53 protein expression and has been found to be associated with an elevated risk of various cancer; especially breast and lung cancer. As the previous case-control studies on the South Asian population have shown controversial results, we performed a meta-analysis to evaluate a precise estimation of the relationship between the TP53 Arg72Pro polymorphism with breast and lung cancer. Methods: A total of 12 related studies on the South Asian population have been included through comprehensive database searching. Six studies were selected for breast cancer meta-analysis involving 950 cases and 882 controls; the other six studies were for lung cancer meta-analysis including 975 cases and 1397 controls. The results have been determined by using the Review Manager (RevMan) 5.3. Additionally, the stability of our analysis was assessed by heterogeneity, publication bias analysis and sensitivity testing. Results: A significantly increased risk of breast cancer was found in Pro allele (Pro vs. Arg), co-dominant model 2 (Pro/Pro vs. Arg/Arg), dominant model (Pro/Pro + Arg/Pro vs. Arg/Arg). In case of lung cancer, significantly increased risk was found in the allele, co-dominant 1, co-dominant 2, co-dominant 3, dominant, and recessive models. No association with other genetic models with breast and lung cancer risk was found in the South Asian population. Conclusions: Our results indicate that TP53 Arg72Pro polymorphism is a risk factor for the development of breast cancer and lung cancer in the South Asian population.     

Impact of Recurrent Floods on the Utilization of Maternal and Newborn Healthcare in Bangladesh

Maternal and Child Health Journal - Floods are one of the most common types of disasters in Bangladesh and lead to direct and indirect impacts on health. The aim of the study was to assess the...     

Sociodemographic determinants of Malaysian household’s use of and expenditure on alcohol: a regional comparison

Abstract

Aims: Alcohol consumption has become a serious public health concern. The objective of the present study is to investigate sociodemographic factors associated with alcohol consumption across regions of Malaysia.

Methods: Data are obtained from the Malaysian Household Expenditure Survey 2014, which contains 10,665 observations. Double-hurdle model is used to examine the consumption decision and amount decision of alcohol among households. Analyses are stratified by regions (Northern, East coast, Central and Southern).

Findings: Results show that age, household size, gender, ethnicity, marital status, education, employment status, location of residence and tobacco consumption are independently associated with alcohol consumption. Households headed by males and well-educated individuals are more likely to consume alcohol and also spend more compared with households headed by females and less-educated individuals. Being employed, non-Bumiputera and tobacco consumption seem to increase the likelihood of consuming alcohol. Household size is negatively associated with the amount spent on alcohol.

Conclusion: In conclusion, sociodemographic factors play an important role in determining alcohol consumption. It appears that factors associated with alcohol consumption vary across regions. Hence, policies that address regional differences in the sociodemographic factors associated with alcohol consumption are needed.     

Assessment of heavy metals by ICP-OES and their impact on insulin stimulating hormone and carbohydrate metabolizing enzymes

Arsenic (As) and cadmium (Cd) have recently emerged as major health concerns owing to their strong association with diabetes mellitus (DM). We aimed to investigate the heavy metals exposure towards incidence of DM at various enzymatic and hormonal levels. Additionally, association of As and Cd with Zinc (Zn, essential metal) was also evaluated. Spot urine samples were collected to assess As, Cd and Zn through ICP-OES. Serum was analyzed by assay method for fasting blood glucose, liver and renal function biomarkers. ELISA was performed to investigate the impact of heavy metals on HbA1c, α-amylase, DPP-IV, IGF-1, leptin, GSH, MDA, SOD, HDL, FFA, TG and interleukin (IL)-6. Association of heavy metals with DM was measured by odds ratio (OR) and level of significance was assessed by Chi-squared test. Unpaired student's t-test was used to compare DM-associated risk factors in heavy metals-exposed and unexposed participants. As and Cd were detectable in 75.4% and 83% participants with mean concentration of 75.5 ppb and 54.5 ppb, respectively. For As exposure, OR in the third quartile was maximum ie 1.34 (95% CI, 0.80 to 2.23), however the result was not statistically significant (P > .05). For Cd exposure, OR in the fourth quartile was considerably high, 1.62 (95% CI, 1.00 to 2.61), with a significant probability value (P < .05). Urinary Cd was negatively associated with Zn. As and Cd exposure increases the incidence of DM in the general population. Impaired hormonal and enzymatic levels in diabetic and non-diabetic exposed participants reflect the multiple organ damage by heavy metal exposure.     

Evaluation of NMU-Induced Breast Cancer Treated with Sirolimus and Sunitinib on Breast Cancer Growth

Objective: To analyze the effect of sirolimus and sunitinib in blocking the tumor growth and to evaluate the expressions of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor-2 (HER2/neu) after treated with sirolimus and sunitinib. Methods: Thirty-two female Sprague Dawley rats at age 21-days old were administered intraperitoneally with N-Methyl-N-Nitroso Urea (NMU), dosed at 70mg/kg body weight. The rats were divided into 4 groups; Group 1 (Control, n=8), Group 2 (Sirolimus, n=8), Group 3 (Sunitinib, n=8) and Group 4 (Sirolimus+Sunitinib, n=8), being treated twice when the tumor reached the size of 14.5±0.5 mm and subsequently sacrificed after 5 days. The protein expressions of ER, PgR and HER2/neu of the tumor tissues were evaluated by using immunohistochemistry analysis. Results: Treatment with sirolimus alone lowered expressions of ER and PgR of breast cancer and reduced tumor size. There was no significant difference of ER and PgR expressions between control and sunitinib treated tumor. Sunitinib treated tumors reduce in diameter after the first treatment, however the diameter increases after the second treatment. Histologically, sunitinib treated tumor did not show any aggressive invasive carcinoma of no special type (NST) histological subtypes. In addition, all NMU-induced tumors are HER2/neu-negative scoring. Conclusion: Sirolimus is neither synergistic nor additive with sunitinib for breast cancer treatment.     

Use,Awareness, Knowledge and Beliefs of Medication During Pregnancy in Malaysia

ObjectivesThis study aimed to assess medication use in pregnant women in Malaysia by measuring use, knowledge, awareness, and beliefs about medications.MethodsThis was an observational, cross-sectional study involving a total of 447 pregnant women who attended the Obstetrics and Gynecology Clinic, Hospital Kuala Lumpur (HKL), Malaysia. A validated, self-administered questionnaire was used to collect participant data.ResultsMost of pregnant women had taken medication during pregnancy and more than half of them (52.8%) showed a poor level of knowledge about the medication use during pregnancy. Eighty-three percent had a poor level of awareness and 56.5% had negative beliefs. Age and education level were significantly associated with the level of knowledge regarding medication use during pregnancy. Multiparous pregnant women, and pregnant women from rural areas were observed to have a higher level of awareness compared with those who lived in urban areas. Use of medication during pregnancy was determined to be significantly associated with education level, and race.ConclusionAlthough there was prevalent use of medication among pregnant women, many had negative beliefs, and insufficient knowledge and awareness about the risks of taking medication during pregnancy. Several sociodemographic characteristics were significantly associated with the use (race and education level), level of knowledge (age and education level), awareness (parity and place of residence), and beliefs (race, education level, and occupation status) towards medication use during pregnancy.     

Responsiveness of the urban primary health care delivery system in Bangladesh: A comparative analysis

This study analyses the responsiveness of outpatient care to assess the quality of urban primary health care among all 5 types of health care providers in Bangladesh, namely, the Urban Primary Health Care Services Delivery Project, the NGO Health Services Delivery Project (NHSDP), NGOs, private hospitals, and the Ministry of Health and Family Welfare (MOHFW). Other than some public‐private comparisons, there is an absolute knowledge gap regarding responsiveness in urban health systems, particularly in the context of Bangladesh, and this gap motivates this study. The study used primary data collected from 810 randomly selected outpatients. The survey used a structured questionnaire on all 7 domains of responsiveness of outpatient care suggested by the World Health Organization. The estimated mean responsiveness score reveals that overall, approximately 33% of the patients rated the responsiveness of the system as poor. In reported responsiveness, the NHSDP was ranked at the top and the MOHFW at the bottom. The latter is quite expected. Overall, prompt attention and autonomy were the worst‐performing domains, and choice of provider, dignity, and clear communication were the better‐performing ones. The results suggest the need to improve the degree of responsiveness of all domains, especially those that are more concerned with access to health care, namely, prompt attention, dignity, clear communication, and confidentiality. The Ministry of Health and Family Welfare facilities should give additional consideration to promote prompt attention, autonomy, and quality of basic amenities. Private facilities should also provide additional stress on improving prompt attention and autonomy. The nontherapeutic quality of health care needs to be emphasized in the medical education system. Further research based on household surveys could be worthwhile to measure responsiveness more comprehensively.     

Effect of sinapic acid on aripiprazole pharmacokinetics in rats: Possible food drug interaction

Dietary supplements and foods can interact with various drugs, leading to possible clinical concerns. This study aimed to investigate the effect of orally administered sinapic acid (SA) on the pharmacokinetics of aripiprazole (APZ) in rats and its possible modulatory effects on hepatic cytochrome P450 (CYP3A2 and CYP2D6) expression in the liver tissues. Single dose and multiple dose parallel groups of wistar rats were categorized into six groups (n = 6 each) which abstained from food for 12 h prior to the experiment, while water was allowed ad libitum. The investigation was carried out for single dose: Group I was treated with normal saline orally for 15 days (normal control). Group II was administered normal saline orally for 15 days and received APZ (3 mg/kg p.o.) on day 15. Group III received SA (20 mg/kg p.o.) for 15 days and received APZ (3 mg/kg p.o.) on day 15. Group IV was treated with SA (20 mg/kg p.o.) for 15 days. For the multiple dose study, Group I was treated with normal saline orally for 15 days (normal control); Group II received APZ (3 mg/kg p.o.) daily for 15 days; Group III was administered with SA (20 mg/kg p.o.) and APZ (3 mg/kg p.o.) for 15 days and Group IV received SA (20 mg/kg p.o.) for 15 days. The group I and IV were kept common in single and multiple dose groups. After last APZ dose, plasma samples were collected and APZ concentrations were determined using an UPLC-MS/MS technique. The pharmacokinetic parameters were calculated using a non-compartmental analysis. The concomitant administration of APZ with SA (as single or multiple dose) resulted in an increase in APZ absorption and a decrease on its systemic clearance. This was associated with a reduction in CYP3A2 and CYP2D6 protein expressions by 33–43% and -71–68% after the single and multiple co-administration, which are two enzymes responsible of the metabolism of APZ. Therefore, a reduction in the metabolic clearance appears to be the mechanism underlying the drug interaction of dietary supplement containing SA with APZ. Therefore, the concomitant administration of SA and APZ should be carefully viewed. Further investigations are required to assess the clinical significance of such observations in humans.