An unbiased lipid phenotyping approach to study the genetic determinants of lipids and their association with coronary heart disease risk factors

Direct infusion high-resolution mass spectrometry (DIHRMS) is a novel, high-throughput approach to rapidly and accurately profile hundreds of lipids in human serum without prior chromatography, facilitating in-depth lipid phenotyping for large epidemiological studies to reveal the detailed associations of individual lipids with coronary heart disease (CHD) risk factors. Intact lipid profiling by DIHRMS was performed on 5662 serum samples from healthy participants in the Pakistan Risk of Myocardial Infarction Study (PROMIS). We developed a novel semi-targeted peak-picking algorithm to detect mass-to-charge ratios in positive and negative ionization modes. We analyzed lipid partial correlations, assessed the association of lipid principal components with established CHD risk factors and genetic variants, and examined differences between lipids for a common genetic polymorphism. The DIHRMS method provided information on 360 lipids (including fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, and sterol lipids), with a median coefficient of variation of 11.6% (range: 5.4–51.9). The lipids were highly correlated and exhibited a range of associations with clinical chemistry biomarkers and lifestyle factors. This platform can provide many novel insights into the effects of physiology and lifestyle on lipid metabolism, genetic determinants of lipids, and the relationship between individual lipids and CHD risk factors

Lossless compression schemes for ECG signals using neural network predictors

This paper presents lossless compression schemes for ECG signals based on neural network predictors and entropy encoders. Decorrelation is achieved by nonlinear prediction in the first stage and encoding of the residues is done by using lossless entropy encoders in the second stage. Different types of lossless encoders, such as Huffman, arithmetic, and runlength encoders, are used. The performances of the proposed neural network predictor-based compression schemes are evaluated using standard distortion and compression efficiency measures. Selected records from MIT-BIH arrhythmia database are used for performance evaluation. The proposed compression schemes are compared with linear predictor-based compression schemes and it is shown that about 11% improvement in compression efficiency can be achieved for neural network predictor-based schemes with the same quality and similar setup. They are also compared with other known ECG compression methods and the experimental results show that superior performances in terms of the distortion parameters of the reconstructed signals can be achieved with the proposed schemes. Copyright (c) 2007 R. Kannan and C. Eswaran

Prospects for Enhancing Efficacy of Radioimmunotherapy

International audienceRadioimmunotherapy has been in use for more than 20 years and has progressed significantly since its efficacy has first been demonstrated in hematology. Yet it still has limitations that prevent its large-scale clinical use. This chapter reviews recent developments to overcome these limitations including new antibody specifici-ties, pretargeting methods, fractionated injections, and the use of alpha emitters. Immuno-PET is also likely to assist in selecting patients for radioimmunotherapy, optimizing injected activities, and noninvasively monitoring therapy efficacy

Early child health in Lahore, Pakistan: V. Feeding patterns

The feeding practices of children (n = 1476) from birth to 24 months, as determined in a longitudinal study, in Lahore, Pakistan, are presented. Four socioeconomic groups at various levels of urbanization were included; a village, periurban slum, urban slum and an upper middle class. Initiation of breastfeeding was delayed in all the neonates. Sixty-five percent of the periurban slum mothers and 45% of the village mothers had not started breastfeeding at 48 hours after the birth of the infant. Prelacteal feedings, especially of herb water and honey, were the norm. Breastfeeding was highly prevalent. Eighty-seven to 98% of the infants in all the areas were breastfed at one month of age. Exclusive breastfeeding was rare, with 9% at one month, declining rapidly with age and being highly influenced by season. Partial breastfeeding was the most common mode of feeding. Water in addition to human milk was given by 45-73% of the mothers living in the urban slum, village and periurban slum at one month of age. Fresh animal milk and/or commercial formula was already being given at 1 month by 22-64% of the mothers in all areas. Commercial formula was the preferred food in the upper middle class, while in the other three areas it was rare and fresh animal milk was mainly used. More than 50% of the mothers in the village and in the periurban slum gave diluted animal milk even beyond the age of 10-15 months. In the upper middle class 50% of the infants were fed semisolids at the age of four months, while in the village, the periurban and the urban slum at 6 months of age only 10%, 12% and 47% of the infants received semisolids. The results of this study indicate that breastfeeding was highly prevalent in the three poorest areas. However, in all the areas initiation of breastfeeding was delayed and prelacteal feeding was the norm. Exclusive breastfeeding was rare, feeding bottles were used by 82-100% of the mothers to feed supplements and human milk substitutes, in the four areas.link_to_subscribed_fulltex

Combination of anti-L1 cell adhesion molecule antibody and gemcitabine or cisplatin improves the therapeutic response of intrahepatic cholangiocarcinoma

<div><p>Cholangiocarcinoma has a poor prognosis and is refractory to conventional chemotherapy and radiation therapy. Improving survival of patients with advanced cholangiocarcinoma urgently requires the development of new effective targeted therapies in combination with chemotherapy. We previously developed a human monoclonal antibody (mAb) Ab417 that binds to both the human and mouse L1 cell adhesion molecule (L1CAM) with high affinities. In the present study, we observed that Ab417 exhibited tumor targeting ability in biodistribution studies and dose-dependent tumor growth inhibition in an intrahepatic cholangiocarcinoma (Choi-CK) xenograft mouse model. Regarding the mechanism of action, Ab417 was internalized into the tumor cells and thereby down-regulated membrane L1CAM, and inhibited tumor growth by reducing tumor cell proliferation <i>in vivo</i>. Gemcitabine inhibited the tumor growth in a dose-dependent manner in the Choi-CK xenograft model. However, cisplatin inhibited the tumor growth moderately and not in a dose-dependent way, suggesting that the tumors may have developed resistance to apoptosis induced by cisplatin. Combined treatment with Ab417 and gemcitabine or cisplatin exerted enhanced tumor growth inhibition compared to treatment with antibody or drug alone. The results suggest that Ab417 in combination with chemotherapy may have potential as a new therapeutic regimen for cholangiocarcinoma. Our study is the first to show an enhanced therapeutic effect of a therapeutic antibody targeting L1CAM in combination with chemotherapy in cholangiocarcinoma models.</p></div