The relationship between birth weight and insulin resistance in childhood

Chronic diseases that are typical of adulthood may originate in intra-uterine life through inadequate fetal development. The present epidemiological cohort study of 506 healthy children aged 5\20138 years evaluated the relationship between birth weight and insulin resistance in an age group that has been assessed in few similar studies. Insulin concentration was determined by chemiluminescence and insulin resistance by the homeostasis model assessment (HOMA). Blood glucose, total cholesterol and fractions (LDL cholesterol and HDL cholesterol) and TAG concentrations were determined by automated enzymatic methods. Linear regression analysis investigated the relationship between birth weight (assessed as a continuous variable and in three categories: small for gestational age, SGA; adequate for gestational age and large for gestational age) and the HOMA index, using backward stepwise selection and biological models to explain the causal pathway of the relationship. There were negativeassociations between birth weight (P < 0·001), SGA (P = 0·027) and the HOMA index, and a positive association between waist circumference (P < 0·001) and the HOMA index. Considering the significant associations between birth weight and waist circumference (P < 0·001) and waist circumference and insulin resistance (P < 0·001), we can probably suspect that lower birth weight is a common cause of higher waist circumference and insulin resistance. In summary, the results of the present study showed increased insulin resistance in apparently healthy, young children, who had lower weight at birth and higher measurements of waist circumference. There is a need to develop public health policies that adopt preventive measures to promote adequate maternal-fetal and child development and enable early diagnosis of metabolic abnormalities

Iron concentrations in breast milk and selected maternal factors of human milk bank donors

FAPESP n. 03/04061-2

Fatores associados à recuperação nutricional de crianças em programa de suplementação alimentar

OBJETIVOS: Identificar os fatores associados à recuperação nutricional de crianças inscritas no Programa de Incentivo ao Combate às Carências Nutricionais (ICCN) no Município de Mogi das Cruzes. MÉTODOS: Foi realizado um ensaio institucional não controlado com 570 crianças inscritas no ICCN, que foram seguidas de julho de 1999 a julho de 2001. O estado nutricional foi avaliado segundo índice altura/idade, sendo consideradas eutróficas as crianças com escore z > - 1; de risco as que apresentaram z > - 2 e < - 1; desnutridas moderadas aquelas com z < - 2 e > - 3; e desnutridas graves as que apresentavam z < - 3. O impacto do ICCN foi analisado através de modelo multivariado com o uso de equações de estimação (GEE - Generalized Estimating Equations), sendo considerado significativo p<0,05. RESULTADOS/CONCLUSÃO: Ao final do seguimento, houve a melhora nutricional das crianças, com um gradiente, sendo maior a recuperação quanto maior a deficiência nutricional inicial. Observaram-se ganhos em altura de 1,12, 0,82, 0,57 e 0,45 desvios-padrão para as desnutridas graves, moderadas, em risco nutricional e eutróficas, respectivamente. Os fatores associados à evolução nutricional das crianças desnutridas foram a idade de 12 a 24 meses ao ingressar no ICCN, o peso ao nascer igual ou superior a 3 kg e o aleitamento materno. Os fatores associados negativamente à evolução nutricional neste grupo foram idade da mãe entre 20 a 40 anos e a ausência de trabalho remunerado materno. Para as crianças em risco, a renda familiar também se mostrou associada à melhor evolução nutricional. A experiência do ICCN em Mogi das Cruzes sugere que os programas de suplementação alimentar têm papel relevante na recuperação nutricional de desnutridos

Immediate reconstruction following breast-conserving surgery: management of the positive surgical margins and influence on secondary reconstruction

The efficacy of breast-conserving surgery for the local control of early breast cancer has been repeatedly evidenced. Although immediate reconstruction following breast-conserving surgery has been described, little information is available regarding surgical management in reoperative settings due to positive margins. We studied the influence of intraoperatively assessed and postoperatively controlled surgical margin status on the type of breast-conserving surgery and report our results regarding complications in a reoperative breast reconstruction scenario. All patients were seen by a multidisciplinary team who recommended breast-conserving surgery. According to the breast volume, ptosis and tumor size/location, the patients were also evaluated by a plastic surgeon, who recommended reconstruction with the appropriate technique. Intraoperative assessment of surgical margins was determined by histological examination of frozen sections. The mean follow-up time was 48months. Two hundred and eighteen patients (88.5 per cent ) underwent breast-conserving surgery and immediate reconstruction. Twelve (5.5 per cent ) patients had a positive tumor margin after review of the permanent section. All patients underwent re-exploration. In 1.3 per cent , a second reconstructive technique was indicated and in 2.2 per cent a skin-sparing mastectomy with total reconstruction was performed. Our findings support the important role of the intraoperative assessment of surgical margins and its interference in the selection of reconstruction techniques and negative margins; however, it will not guarantee complete excision of the tumor. Success depends on coordinated planning with the oncologic surgeon and careful intraoperative management

Classification of breast masses using a committee machine of artificial neural networks

This work proposes a new approach using a committee machine of artificial neural networks to classify masses found in mammograms as benign or malignant. Three shape factors, three edge-sharpness measures, and 14 texture measures are used for the classification of 20 regions of interest (ROIs) related to malignant tumors and 37 ROIs related to benign masses. A group of multilayer perceptrons (MLPs) is employed as a committee machine of neural network classifiers. The classification results are reached by combining the responses of the individual classifiers. Experiments involving changes in the learning algorithm of the committee machine are conducted. The classification accuracy is evaluated using the area A. under the receiver operating characteristics (ROC) curve. The A, result for the committee machine is compared with the A, results obtained using MLPs and single-layer perceptrons (SLPs), as well as a linear discriminant analysis (LDA) classifier Tests are carried out using the student's t-distribution. The committee machine classifier outperforms the MLP SLP, and LDA classifiers in the following cases: with the shape measure of spiculation index, the A, values of the four methods are, in order 0.93, 0.84, 0.75, and 0.76; and with the edge-sharpness measure of acutance, the values are 0.79, 0.70, 0.69, and 0.74. Although the features with which improvement is obtained with the committee machines are not the same as those that provided the maximal value of A(z) (A(z) = 0.99 with some shape features, with or without the committee machine), they correspond to features that are not critically dependent on the accuracy of the boundaries of the masses, which is an important result. (c) 2008 SPIE and IS&T.

Polydimethylsiloxane: a new contrast material for localization of occult breast lesions

Background. The radioguided localization of occult breast lesions (ROLL) technique often utilizes iodinated radiographic contrast to assure that the local injection of (99m)Tc-MAA corresponds to the location of the lesion under investigation. However, for this application, this contrast has several shortcomings. The objective of this study was to evaluate the safety, effectiveness and technical feasibility of the use of polydimethylsiloxane (PDMS) as radiological contrast and tissue marker in ROLL. Materials and methods. The safety assessment was performed by the acute toxicity study in Wistar rats (n = 50). The radiological analysis of breast tissue (n = 32) from patients undergoing reductive mammoplasty was used to verify the effectiveness of PDMS as contrast media. The technical feasibility was evaluated through the scintigraphic and histologic analysis. Results. We found no toxic effects of PDMS for this use during the observational period. It has been demonstrated in human breast tissue that the average diameter of the tissue marked by PDMS was lower than when marked by the contrast medium (p <0.001). PDMS did not interfere with the scintigraphic uptake (p = 0.528) and there was no injury in histological processing of samples. Conclusions. This study demonstrated not only the superiority of PDMS as radiological contrast in relation to the iodinated contrast, but also the technical feasibility for the same applicability in the ROLL.

Breast phantom with silicone implant for evaluation in conventional mammography

With the increased incidence of cancer and a similarly increased number of surgeries for insertion of silicone breast implants, it is necessary to assess the effect of such material within the breast tissue, particularly in mammography, because of the reduction in the power of breast cancer diagnosis. In this work, we introduce a breast phantom with silicone implants in order to evaluate the influence of the implant on the visibility of the main mammographic findings: fibers, microcalcifications and tumor masses. In this proposed phantom, the breast tissue was simulated using gel paraffin. In the optical density of phantom mammograms with implants, a reduction in breast tissue visibility was seen corresponding to 23% when compared to a phantom without silicone implants. This poor visibility was due to the X-ray beam scattering on silicone material; this effect produced a loss of visibility in the areas adjacent to the implant. It is expected that the proposed phantom model may be used as a device for the establishment of a technical standard for these types of procedures.

Analysis of breast cancer by small angle X-ray scattering (SAXS)

Small angle X-ray scattering (SAXS) images of normal breast tissue and benign and malignant breast tumour tissues, fixed in formalin, were measured at the momentum transfer range of 0.063 nm(-1) <= q (=4 pi sin(theta/2)/lambda) <= 2.720 nm(-1). Four intrinsic parameters were extracted from the scattering profiles (1D SAXS image reduced) and, from the combination of these parameters, another three parameters were also created. All parameters, intrinsic and derived, were subject to discriminant analysis, and it was verified that parameters such as the area of diffuse scatter at the momentum transfer range 0.50 <= q <= 0.56 nm(-1), the ratio between areas of fifth-order axial and third-order lateral peaks and third-order axial spacing provide the most significant information for diagnosis (p < 0.001). Thus, in this work it was verified that by combining these three parameters it was possible to classify human breast tissues as normal, benign lesion or malignant lesion with a sensitivity of 83% and a specificity of 100%.

Identification of Neoplasias of Breast Tissues Using a Powder Diffractometer

An investigation was carried out to study the potential use of the angular distribution of scattered photons by human breast samples for a rapid identification of neoplasias of breast tissues. This technique has possible applications as diagnostic aid for breast cancer. In this work, a commercial powder diffractometer was used to obtain the scattering profiles from breast tissues histopathologically classified as normal breast tissues, fibroadenomas (benign breast diseases) and carcinomas (malignant breast diseases), in the interval 0.02 angstrom(-1) < x < 0.62 angstrom(-1). The experimental methods and data corrections are discussed in detail, and they included background subtraction, polarization, self-attenuation and geometric effects. The validation of the experimental procedure was achieved through an analysis of water sample. The results showed that the scattering profile is a unique impression of each type of tissue, being correlated with their microscopic morphological features. Multivariate analysis was applied to these profiles in order to verify if the information carried by these scattering profiles allow the differentiation between normal, benign and malignant breast tissues. The statistical analysis results showed that a correct identification of 75% of the analyzed samples is accomplished. The values of sensibility and specificity of this method in correctly differentiating between normal and neoplastic samples were 95.6% and 82.3%, respectively, while the values for differentiation between benign and malignant neoplasias were 78.6% and 62.5%. These initial results indicate the feasible use of commercial powder diffractometer to provide a rapid diagnostic with a high sensitivity.

Poly (A)(+) Transcriptome Assessment of ERBB2-Induced Alterations in Breast Cell Lines

We report the first quantitative and qualitative analysis of the poly (A)(+) transcriptome of two human mammary cell lines, differentially expressing (human epidermal growth factor receptor) an oncogene over-expressed in approximately 25% of human breast tumors. Full-length cDNA populations from the two cell lines were digested enzymatically, individually tagged according to a customized method for library construction, and simultaneously sequenced by the use of the Titanium 454-Roche-platform. Comprehensive bioinformatics analysis followed by experimental validation confirmed novel genes, splicing variants, single nucleotide polymorphisms, and gene fusions indicated by RNA-seq data from both samples. Moreover, comparative analysis showed enrichment in alternative events, especially in the exon usage category, in ERBB2 over-expressing cells, data indicating regulation of alternative splicing mediated by the oncogene. Alterations in expression levels of genes, such as LOX, ATP5L, GALNT3, and MME revealed by large-scale sequencing were confirmed between cell lines as well as in tumor specimens with different ERBB2 backgrounds. This approach was shown to be suitable for structural, quantitative, and qualitative assessment of complex transcriptomes and revealed new events mediated by ERBB2 overexpression, in addition to potential molecular targets for breast cancer that are driven by this oncogene.

Adherence to cervical and breast cancer programs is crucial to improving screening performance

Introduction: Cervical and breast cancer are the most common malignancies among women worldwide. Effective screening can facilitate early detection and dramatically reduce mortality rates. The interface between those screening patients and patients most needing screening is complex, and women in remote areas of rural counties face additional barriers that limit the effectiveness of cancer prevention programs. This study compared various methods to improve compliance with mass screening for breast and cervical cancer among women in a remote, rural region of Brazil. Methods: In 2003, a mobile unit was used to perform 10 156 mammograms and Papanicolaou smear tests for women living in the Barretos County region of Sao Paulo state, Brazil (consisting of 19 neighbouring cities). To reach the women, the following community outreach strategies were used: distribution of flyers and pamphlets; media broadcasts (via radio and car loudspeakers); and community healthcare agents (CHCAs) making home visits. Results: The most useful intervention appeared to be the home visits by healthcare agents or CHCAs. These agents of the Family Health Programme of the Brazilian Ministry of Health reached an average of 45.6% of those screened, with radio advertisements reaching a further 11.9%. The great majority of the screened women were illiterate or had elementary level schooling (80.9%) and were of 'poor' or 'very poor' socioeconomic class (67.2%). Conclusions: Use of a mobile screening unit is a useful strategy in developing countries where local health systems have inadequate facilities for cancer screening in underserved populations. A multimodal approach to community outreach strategies, especially using CHCAs and radio advertisements, can improve the uptake of mass screening in low-income, low-educational background female populations.

Multi-trait and random regression mature weight heritability and breeding value estimates in Nelore cattle

Mature weight breeding values were estimated using a multi-trait animal model (MM) and a random regression animal model (RRM). Data consisted of 82 064 weight records from 8 145 animals, recorded from birth to eight years of age. Weights at standard ages were considered in the MM. All models included contemporary groups as fixed effects, and age of dam (linear and quadratic effects) and animal age as covariates. In the RRM, mean trends were modelled through a cubic regression on orthogonal polynomials of animal age and genetic maternal and direct and maternal permanent environmental effects were also included as random. Legendre polynomials of orders 4, 3, 6 and 3 were used for animal and maternal genetic and permanent environmental effects, respectively, considering five classes of residual variances. Mature weight (five years) direct heritability estimates were 0.35 (MM) and 0.38 (RRM). Rank correlation between sires' breeding values estimated by MM and RRM was 0.82. However, selecting the top 2% (12) or 10% (62) of the young sires based on the MM predicted breeding values, respectively 71% and 80% of the same sires would be selected if RRM estimates were used instead. The RRM modelled the changes in the (co) variances with age adequately and larger breeding value accuracies can be expected using this model.

Variability in Estrogen-Metabolizing Genes and Their Association with Genomic Instability in Untreated Breast Cancer Patients and Healthy Women

In the present study, we investigated the relationship between polymorphisms in the estrogen-metabolizing genes CYP17, CYP1B1, CYP1A1, and COMT and genomic instability in the peripheral blood lymphocytes of 62 BC patients and 62 controls considering that increased or prolonged exposure to estrogen can damage the DNA molecule and increase the genomic instability process in breast tissue. Our data demonstrated increased genomic instability in BC patients and that individuals with higher frequencies of MN exhibited higher risk to BC when belonging Val/Met genotype of the COMT gene. We also observed that CYP17 and CYP1A1 polymorphisms can modify the risk to BC depending on the menopause status. We can conclude that the genetic background in estrogen metabolism pathway can modulate chromosome damage in healthy controls and patients and thereby influence the risk to BC. These findings suggest the importance to ally biomarkers of susceptibility and effects to estimate risk groups.

Differential expression of HIF-1 alpha in CD44(+)CD24(-/) (low) breast ductal carcinomas

Background: Cancer stem cell (CSC) hypothesis postulates that tumors are maintained by a self-renewing CSC population that is also capable of differentiating into non-self-renewing cell populations that constitute the bulk of tumor. Stem cells renewal and differentiation can be directly influenced by the oxygen levels of determined tissues, probably by the reduction of oxidative DNA damage in hypoxic regions, thus leading to a friendlier microenvironment, regarding to clonal expansion and for resistance to chemotherapeutic regimens. Furthermore, there have been strong data indicating a pivotal role of hypoxic niche in cancer stem cells development. There are evidence that hypoxia could drive the maintenance of CSC, via HIF-1 alpha expression, but it still to be determined whether hypoxia markers are expressed in breast tumors presenting CD44(+)CD24(-/low) immunophenotype. Methods: Immunohistochemical analysis of CD44(+)CD24(-/low) expression and its relationship with hypoxia markers and clinical outcome were evaluated in 253 samples of breast ductal carcinomas. Double-immunolabeling was performed using EnVision Doublestain System (Dako, Carpinteria, CA, USA). Slides were then scanned into high-resolution images using Aperio ScanScope XT and then, visualized in the software Image Scope (Aperio, Vista, CA, USA). Results: In univariate analysis, CD44(+)CD24(-/low) expression showed association with death due to breast cancer (p = 0.035). Breast tumors expressing CD44(+)CD24(-/low) immunophenotype showed relationship with HIF-1 alpha (p = 0.039) and negativity for HER-2 (p = 0.013). Conclusion: Considering that there are strong evidences that the fraction of a tumour considered to be cancer stem cells is plastic depending upon microenvironmental signals, our findings provide further evidence that hypoxia might be related to the worse prognosis found in CD44(+)CD24(-/low) positive breast tumors.

Estimates of genetic trend for carcass traits in a commercial broiler line

Data from the slaughter of 24,001 chickens that were part of a selection program for the production of commercial broilers were used to estimate genetic trend for absolute carcass (CW), breast meat (BRW), and leg (LW) weights, and relative carcass (CY), breast meat (BRY), and leg (LY) weights. The components of (co) variance and breeding values of individuals were obtained by the restricted maximum likelihood method applied to animal models. The relationship matrix was composed of 132,442 birds. The models included as random effects, maternal additive genetic and permanent environmental for CW, BRW, LW, CY, and BRY, and only maternal permanent environmental for LY, besides the direct additive genetic and residual effects, and as fixed effects, hatch week, parents' mating group and sex. The estimates of genetic trend were obtained by average regression of breeding value on generation, and the average genetic trend was estimated by regression coefficients. The genetic trends for CW (+ 6.0336 g/generation), BRW (+ 3.6723 g/generation), LW (+ 1.5846 g/generation), CY (+ 0.1195%/generation), and BRY (+ 0.1388%/generation) were positive, and they were in accordance with the objectives of the selection program for these traits. The genetic trend for LY(-0.0019%/generation) was negative, possibly due to the strong emphasis on selection for BRY and the negative correlations between these two traits.