Association of HADHA expression with the risk of breast cancer: targeted subset analysis and meta-analysis of microarray data

<p>Abstract</p> <p>Background</p> <p>The role of n-3 fatty acids in prevention of breast cancer is well recognized, but the underlying molecular mechanisms are still unclear. In view of the growing need for early detection of breast cancer, Graham et al. (2010) studied the microarray gene expression in histologically normal epithelium of subjects with or without breast cancer. We conducted a secondary analysis of this dataset with a focus on the genes (n = 47) involved in fat and lipid metabolism. We used stepwise multivariate logistic regression analyses, volcano plots and false discovery rates for association analyses. We also conducted meta-analyses of other microarray studies using random effects models for three outcomes--risk of breast cancer (380 breast cancer patients and 240 normal subjects), risk of metastasis (430 metastatic compared to 1104 non-metastatic breast cancers) and risk of recurrence (484 recurring versus 890 non-recurring breast cancers).</p> <p>Results</p> <p>The <it>HADHA </it>gene [hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein), alpha subunit] was significantly under-expressed in breast cancer; more so in those with estrogen receptor-negative status. Our meta-analysis showed an 18.4%-26% reduction in <it>HADHA </it>expression in breast cancer. Also, there was an inconclusive but consistent under-expression of <it>HADHA </it>in subjects with metastatic and recurring breast cancers.</p> <p>Conclusions</p> <p>Involvement of mitochondria and the mitochondrial trifunctional protein (encoded by <it>HADHA </it>gene) in breast carcinogenesis is known. Our results lend additional support to the possibility of this involvement. Further, our results suggest that targeted subset analysis of large genome-based datasets can provide interesting association signals.</p

Association of Urinary Phthalates with Self-Reported Eye Affliction/Retinopathy in Individuals with Diabetes: National Health and Nutrition Examination Survey, 2001-2010

Background. An epidemiological association between exposure to phthalates and type 2 diabetes (T2D) is known. However, the potential role of environmental phthalates in the complications of T2D is unknown. Methods. Using data from the National Health and Nutrition Examination Survey (NHANES) 2001-2010, we studied the association of 12 urinary phthalate metabolites with self-reported eye affliction/retinopathy in 1,004 participants with diabetes. Data from retinal imaging was used to validate this outcome. Independence of the phthalates→T2D association was studied by adjusting for age, sex, race, marital status, educational attainment, poverty income ratio, physical activity, glycated hemoglobin levels, total serum cholesterol, serum high-density lipoprotein cholesterol, serum triglycerides, blood pressure, duration of diabetes, total calorie intake, and obesity. Results. Self-reported eye affliction/retinopathy had 82% accuracy with Cohen\u27s kappa of 0.31 (p \u3c 0.001). Urinary mono-n-octyl phthalate (MOP) was independently associated with the likelihood of self-reported eye affliction/retinopathy in subjects with T2D after accounting for all the confounders. This significance of this association was robust to the potential misclassification in cases and controls of retinopathy. Further, a significant dose-response relationship between MOP and self-reported eye affliction/retinopathy was demonstrable. Conclusions. We show a novel epidemiological link between the environment and diabetic complications in NHANES 2001-2010 participants

Association of Urinary Phthalates with Self-Reported Eye Affliction/Retinopathy in Individuals with Diabetes: National Health and Nutrition Examination Survey, 2001-2010

Background. An epidemiological association between exposure to phthalates and type 2 diabetes (T2D) is known. However, the potential role of environmental phthalates in the complications of T2D is unknown. Methods. Using data from the National Health and Nutrition Examination Survey (NHANES) 2001-2010, we studied the association of 12 urinary phthalate metabolites with self-reported eye affliction/retinopathy in 1,004 participants with diabetes. Data from retinal imaging was used to validate this outcome. Independence of the phthalates→T2D association was studied by adjusting for age, sex, race, marital status, educational attainment, poverty income ratio, physical activity, glycated hemoglobin levels, total serum cholesterol, serum high-density lipoprotein cholesterol, serum triglycerides, blood pressure, duration of diabetes, total calorie intake, and obesity. Results. Self-reported eye affliction/retinopathy had 82% accuracy with Cohen\u27s kappa of 0.31 (p \u3c 0.001). Urinary mono-n-octyl phthalate (MOP) was independently associated with the likelihood of self-reported eye affliction/retinopathy in subjects with T2D after accounting for all the confounders. This significance of this association was robust to the potential misclassification in cases and controls of retinopathy. Further, a significant dose-response relationship between MOP and self-reported eye affliction/retinopathy was demonstrable. Conclusions. We show a novel epidemiological link between the environment and diabetic complications in NHANES 2001-2010 participants

Approaches towards Implementation of Multi-bit Digital Receiver using Fast Fourier Transform

This paper compares different digital receiver signal processing schemes as applied to current ESM/RWR systems. The schemes include fast fourier transform (FFT)-based, FIR filter-based and mixed architectures. Use of polyphase FFT and IIR filters is also discussed. The specifications and signal processing requirements of a modern digital electronic warfare (EW) receiver are discussed. The design procedures and architectures for all the schemes are brought out. The tradeoffs involved in selection of different parameters for these schemes are also discussed. The digital receiver schemes are modeled and analyzed for different metrics such as, Parameter measurement accuracies, Pulse handling capability, Frequency separation capability, Number of multipliers required for implementation etc. The analysis is done for a 500 MHz BW digital receiver and assumes 8 bit ADC in the front end. The results obtained for the comparison are discussed in the paper. Limited simulations show that overlapped FFT scheme is a better approach for digital receiver processing.Defence Science Journal, 2013, 63(2), pp.198-203, DOI:http://dx.doi.org/10.14429/dsj.63.426

Association of umbilical cord blood lead with neonatal behavior at varying levels of exposure

BACKGROUND: In the light of the ongoing debate about lowering the cut-off for acceptable blood lead level to <5 μg/dL from the currently recommended level of <10 μg/dL, we considered whether prenatal exposure to varying levels of lead is associated with similar or disparate effects on neonatal behavior. METHODS: Using Brazelton's Neonatal Behavioral Assessment Scale (NBAS), an epidemiological approach and robust statistical techniques like multivariate linear regression, logistic regression, Poisson regression and structural equations modeling analyses we estimated the simultaneous indirect effects of umbilical cord blood lead (CBL) levels and other neonatal covariates on the NBAS clusters. RESULTS: We observed that when analyzed in all study subjects, the CBL levels independently and strongly influenced autonomic stability and abnormal reflexes clusters. However, when the analysis was restricted to neonates with CBL <10 μg/dL, CBL levels strongly influenced the range of state, motor and autonomic stability clusters. Abnormal walking reflex was consistently associated with an increased CBL level irrespective of the cut-off for CBL, however, only at the lower cut-offs were the predominantly behavioral effects of CBL discernible. CONCLUSION: Our results further endorse the need to be cognizant of the detrimental effects of blood lead on neonates even at a low-dose prenatal exposure

Detection and Risk Stratification of Women at High Risk of Preterm Birth in Rural Communities near Nagpur, India

Background: Presently, preterm birth is globally the leading cause of neonatal mortality. Prompt community based identification of women at high risk for preterm births (HRPB) can either help to avert preterm births or avail effective interventions to reduce neonatal mortality due to preterm births. We evaluated the performance of a package to train community workers to detect the presence of signs or symptoms of HRPB. Methods: Pregnant women enrolled in the intervention arm of a cluster randomized trial of Antenatal Corticosteroids (ACT Trial) conducted at Nagpur, India were informed about 4 directly observable signs and symptoms of preterm labor. Community health workers actively monitored these women from 24 to 36 weeks of gestation for these signs or symptoms. If they were present (HRPB positive) the identified women were brought to government health facilities for assessment and management. HRPB positive could also be determined by the provider if the woman presented directly to the facility. Risk stratification was based on the number of signs or symptoms present. The outcome of preterm birth was based on the clinical assessment of gestational age \u3c 37 weeks at delivery or a birth weight of \u3c2000 g. Results: Between July 1, 2012 and 30 November, 2013, 686 of 7050 (9.7%) pregnant women studied, delivered preterm. 732 (10.4%) women were HRPB positive, of whom 333 (45.5%) delivered preterm. Of the remaining 6318(89.6%) HRPB negative women 353 (5.6%) delivered preterm. The likelihood ratio (LR) of a preterm birth in the HRPB positives was 8.14 (95% confidence interval 7.16-9.26). The LR of a preterm birth increased in women who had more signs or symptoms of HRBP (p \u3c 0.00001). More signs or symptoms of HRPB were also associated with a shorter time to delivery, lower birth weight and higher rates of stillbirths, neonatal deaths and postnatal complications. Addition of risk stratification improved the prediction of preterm delivery (Integrated Discrimination Improvement 17% (95% CI 15-19%)). Conclusions: The package for detection of signs and symptoms of HRPB is feasible, promising and likely to improve management of preterm labor. Trial registration: NCT01073475 on February 21, 2010 and NCT01084096 on March 9, 2010

Influence of Zinc Supplementation in Acute Diarrhea Differs by the Isolated Organism

Zinc supplementation is recommended in all acute diarrheas in children from developing countries. We aimed to assess whether zinc supplementation would be equally effective against all the common organisms associated with acute diarrheas. We used data on 801 children with acute diarrhea recruited in a randomized, double blind controlled trial (ISRCTN85071383) of zinc and copper supplementation. Using prespecified subgroup analyses, multidimensionality reduction analyses, tests of heterogeneity, and stepwise logistic regression for tests of interactions, we found that the influence of zinc on the risk of diarrhea for more than 3 days depended on the isolated organism—beneficial in Klebsiella, neutral in Esherichia coli and parasitic infections, and detrimental in rotavirus coinfections. Although we found similar results for the outcome of high stool volume, the results did not reach statistical significance. Our findings suggest that the current strategy of zinc supplementation in all cases of acute diarrheas in children may need appropriate fine tuning to optimize the therapeutic benefit based on the causative organism, but further studies need to confirm and extend our findings

TASTE MASKING OF DONEPEZIL HYDROCHLORIDE USING DIFFERENT ION EXCHANGE RESINS- A COMPARATIVE STUDY

Taste mainly depends on the physiology, sensitivity and structure of taste buds. It is an important parameter in administering drugs orally. Bitter taste is a major limitation to patient compliance. Donepezil hydrochloride (DH) is a bitter drug used in Alzheimer's disease. Amongst the many techniques for taste masking, using ion exchange resins has been extensively reported. The technique of forming tasteless complexes with bitter drugs involves selection of most appropriate exchanger and optimization of complexing ratio. The aim of the present work was to select the best cationic exchanger amongst Indion 414, Indion 234 and Indion 214. All parameters were optimized to produce drug-loaded tasteless complexes. Complexation was carried out using batch process prior to which, acid-alkali activation was performed to remove adsorbed impurities from the resin bed surface and hence improve loading efficiency. UV-spectrophotometric method was used to determine percent drug loading. The molecular properties of drug resin complexes were studied using Fourier Transform Infra-red Spectroscopy, Differential Scanning Calorimetry and Xray Powder Diffraction which confirmed complexation. Indion 414 was found to give highest drug loading and minimal drug was released from the complex at salivary pH. Key words: Donepezil HCl, Ion exchange resins, Molecular properties, Taste maskin

Male breast cancer: is the scenario changing

<p>Abstract</p> <p>Background</p> <p>The overall incidence of male breast cancer is around 1% of all breast cancers and is on the rise. In this review we aim to present various aspects of male breast cancer with particular emphasis on incidence, risk factors, patho-physiology, treatment, prognostic factors, and outcome.</p> <p>Methods</p> <p>Information on all aspects of male breast cancer was gathered from available relevant literature on male breast cancer from the MEDLINE database over the past 32 years from 1975 to 2007. Various reported studies were scrutinized for emerging evidence. Incidence data were also obtained from the IARC, Cancer Mondial database.</p> <p>Conclusion</p> <p>There is a scenario of rising incidence, particularly in urban US, Canada and UK. Even though more data on risk factors is emerging about this disease, more multi-institutional efforts to pool data with large randomized trials to show treatment and survival benefits are needed to support the existing vast emerging knowledge about the disease.</p

Therapeutic Value of Zinc Supplementation in Acute and Persistent Diarrhea: A Systematic Review

BACKGROUND: For over a decade, the importance of zinc in the treatment of acute and persistent diarrhea has been recognized. In spite of recently published reviews, there remain several unanswered questions about the role of zinc supplementation in childhood diarrhea in the developing countries. Our study aimed to assess the therapeutic benefits of zinc supplementation in the treatment of acute or persistent diarrhea in children, and to examine the causes of any heterogeneity of response to zinc supplementation. METHODS AND FINDINGS: EMBASE, MEDLINE and CINAHL databases were searched for published reviews and meta-analyses on the use of zinc supplementation for the prevention and treatment of childhood diarrhea. Additional RCTs published following the meta-analyses were also sought. The reviews and published RCTs were qualitatively mapped followed by updated random-effects meta-analyses, subgroup meta-analyses and meta-regression to quantify and characterize the role of zinc supplementation with diarrhea-related outcomes. We found that although there was evidence to support the use of zinc to treat diarrhea in children, there was significant unexplained heterogeneity across the studies for the effect of zinc supplementation in reducing important diarrhea outcomes. Zinc supplementation reduced the mean duration of diarrhea by 19.7% but had no effect on stool frequency or stool output, and increased the risk of vomiting. Our subgroup meta-analyses and meta-regression showed that age, stunting, breast-feeding and baseline zinc levels could not explain the heterogeneity associated with differential reduction in the mean diarrheal duration. However, the baseline zinc levels may not be representative of the existing zinc deficiency state. CONCLUSIONS: Understanding the predictors of zinc efficacy including the role of diarrheal disease etiology on the response to zinc would help to identify the populations most likely to benefit from supplementation. To improve the programmatic use of zinc, further evaluations of the zinc salts used, the dose, the frequency and duration of supplementation, and its acceptability are required. The significant heterogeneity of responses to zinc suggests the need to revisit the strategy of universal zinc supplementation in the treatment children with acute diarrhea in developing countries