Epithelial cells in nipple aspirate fluid and subsequent breast cancer risk: A historic prospective study

<p>Abstract</p> <p>Background</p> <p>Past studies have shown that women with abnormal cytology or epithelial cells in nipple aspirate fluid (NAF) have an increased relative risk (RR) of breast cancer when compared to women from whom NAF was attempted but not obtained (non-yielders). This study analyzed NAF results from a group of women seen in a breast clinic between 1970–1991 (N = 2480). Our analysis presented here is an aggregate of two sub-groups: women with questionnaire data (n = 712) and those with NAF visits beginning in 1988 (n = 238), the year in which cancer case information was uniformly collected in California.</p> <p>Methods</p> <p>Cytological classification was determined for a group of 946 women using the most abnormal epithelial cytology observed in fluid specimens. Breast cancer incidence and mortality status was determined through June 2006 using data from the California Cancer Registry, California Vital Statistics and self-report. We estimated odd ratios (ORs) for breast cancer using logistic regression analysis, adjusting for age. We analyzed breast cancer risk related to abnormality of NAF cytology using non-yielders as the referent group and breast cancer risk related to the presence or absence of epithelial cells in NAF, using non-yielders/fluid without epithelial cells as the referent group.</p> <p>Results</p> <p>Overall, 10% (93) of the 946 women developed breast cancer during the follow-up period. Age-adjusted ORs and 95% confidence intervals (C.I.) compared to non-yielders were 1.4 (0.3 to 6.4), 1.7 (0.9 to 3.5), and 2.0 (1.1 to 3.6) for women with fluid without epithelial cells, normal epithelial cells and hyperplasia/atypia, respectively. Comparing the presence or absence of epithelial cells in NAF, women with epithelial cells present in NAF were more likely to develop breast cancer than non-yielders or women with fluid without epithelial cells (RR = 1.9, 1.2 to 3.1).</p> <p>Conclusion</p> <p>These results support previous findings that 1) women with abnormal epithelial cells in NAF have an increased risk of breast cancer when compared to non-yielders or women with normal epithelial cells in NAF and 2) women with epithelial cells present in NAF have an increased risk of breast cancer when compared to non-yielders or women who had NAF without epithelial cells present.</p

May Measurement Month 2017: an analysis of blood pressure screening in the Philippines-South-East Asia and Australasia

Cardiovascular diseases remain the Philippines' leading cause of mortality, with hypertension as a prevalent contributory risk factor. We took part in May Measurement Month 2017 (MMM17), a global initiative to raise awareness of high blood pressure (BP) and to serve as a temporary solution to the lack of screening programs worldwide. Following the standard MMM protocol, data for 271 604 screened individuals were submitted from the Philippines. After multiple imputation, 91 994 (34.3%) were hypertensive; 28 662 out of 205 158 participants (14.0%) not receiving treatment had hypertension; and of the 60 370 receiving treatment, 25 144 (41.6%) had uncontrolled BP. Blood pressures were significantly higher in the overweight and obese, current smokers, in participants receiving antihypertensive medication, those with previous myocardial infarction or stroke. The BP measurements were relatively lower when taken on the left arm, and in pregnant women. A slightly higher systolic BP was noted in participants who reported no alcohol intake. Blood pressures recorded during the weekends were highest, and the lowest readings were obtained on Tuesdays. MMM17 was the largest BP screening campaign conducted in the Philippines. Opportunistic BP screening, harnessing volunteers, are a cost-effective public health measure to improve awareness and treatment rates of raised BP. These may help provide additional information that can guide medical practitioners and health officials in drafting preventive and therapeutic measures to improve control rates and long-term outcomes of hypertensive individuals in the population

Idelalisib sensitivity and mechanisms of disease progression in relapsed TCF3-PBX1 acute lymphoblastic leukemia

Peer reviewe

RT-qPCR reveals opsin gene upregulation associated with age and sex in guppies (Poecilia reticulata) - a species with color-based sexual selection and 11 visual-opsin genes

<p>Abstract</p> <p>Background</p> <p>PCR-based surveys have shown that guppies (<it>Poecilia reticulata</it>) have an unusually large visual-opsin gene repertoire. This has led to speculation that opsin duplication and divergence has enhanced the evolution of elaborate male coloration because it improves spectral sensitivity and/or discrimination in females. However, this conjecture on evolutionary connections between opsin repertoire, vision, mate choice, and male coloration was generated with little data on gene expression. Here, we used RT-qPCR to survey visual-opsin gene expression in the eyes of males, females, and juveniles in order to further understand color-based sexual selection from the perspective of the visual system.</p> <p>Results</p> <p>Juvenile and adult (male and female) guppies express 10 visual opsins at varying levels in the eye. Two opsin genes in juveniles, <it>SWS2B </it>and <it>RH2-2</it>, accounted for >85% of all visual-opsin transcripts in the eye, excluding <it>RH1</it>. This relative abundance (RA) value dropped to about 65% in adults, as <it>LWS-A180 </it>expression increased from approximately 3% to 20% RA. The juvenile-to-female transition also showed <it>LWS-S180 </it>upregulation from about 1.5% to 7% RA. Finally, we found that expression in guppies' <it>SWS2-LWS </it>gene cluster is negatively correlated with distance from a candidate locus control region (LCR).</p> <p>Conclusions</p> <p>Selective pressures influencing visual-opsin gene expression appear to differ among age and sex. <it>LWS </it>upregulation in females is implicated in augmenting spectral discrimination of male coloration and courtship displays. In males, enhanced discrimination of carotenoid-rich food and possibly rival males are strong candidate selective pressures driving <it>LWS </it>upregulation. These developmental changes in expression suggest that adults possess better wavelength discrimination than juveniles. Opsin expression within the <it>SWS2-LWS </it>gene cluster appears to be regulated, in part, by a common LCR. Finally, by comparing our RT-qPCR data to MSP data, we were able to propose the first opsin-to-λ_maxassignments for all photoreceptor types in the cone mosaic.</p

A Second-Generation Device for Automated Training and Quantitative Behavior Analyses of Molecularly-Tractable Model Organisms

A deep understanding of cognitive processes requires functional, quantitative analyses of the steps leading from genetics and the development of nervous system structure to behavior. Molecularly-tractable model systems such as Xenopus laevis and planaria offer an unprecedented opportunity to dissect the mechanisms determining the complex structure of the brain and CNS. A standardized platform that facilitated quantitative analysis of behavior would make a significant impact on evolutionary ethology, neuropharmacology, and cognitive science. While some animal tracking systems exist, the available systems do not allow automated training (feedback to individual subjects in real time, which is necessary for operant conditioning assays). The lack of standardization in the field, and the numerous technical challenges that face the development of a versatile system with the necessary capabilities, comprise a significant barrier keeping molecular developmental biology labs from integrating behavior analysis endpoints into their pharmacological and genetic perturbations. Here we report the development of a second-generation system that is a highly flexible, powerful machine vision and environmental control platform. In order to enable multidisciplinary studies aimed at understanding the roles of genes in brain function and behavior, and aid other laboratories that do not have the facilities to undergo complex engineering development, we describe the device and the problems that it overcomes. We also present sample data using frog tadpoles and flatworms to illustrate its use. Having solved significant engineering challenges in its construction, the resulting design is a relatively inexpensive instrument of wide relevance for several fields, and will accelerate interdisciplinary discovery in pharmacology, neurobiology, regenerative medicine, and cognitive science

“We ought to eat in order to work, not vice versa”: MacIntyre, practices, and the best work for humankind.

This paper draws a distinction between ‘right MacIntyreans’ who are relatively optimistic that MacIntyre’s vision of ethics can be realised in capitalist society, and ‘left MacIntyreans’ who are sceptical about this possibility, and aims to show that the ‘left MacIntyrean’ position is a promising perspective available to business ethicists. It does so by arguing for a distinction between ‘community-focused’ practices and ‘excellence-focused’ practices. The latter concept fulfils the promise of practices to provide us with an understanding of the best work for humankind and highlights the affinities between MacIntyre’s concept of a practice and Marx’s conception of good work as free, creative activity. The paper concludes with a suggestion that we reflect on the best forms of work so that we can strive to ensure the very best activities, those most consonant with our flourishing, one day become available to all

Cell-type–specific eQTL of primary melanocytes facilitates identification of melanoma susceptibility genes

Most expression quantitative trait locus (eQTL) studies to date have been performed in heterogeneous tissues as opposed to specific cell types. To better understand the cell-type–specific regulatory landscape of human melanocytes, which give rise to melanoma but account for <5% of typical human skin biopsies, we performed an eQTL analysis in primary melanocyte cultures from 106 newborn males. We identified 597,335 cis-eQTL SNPs prior to linkage disequilibrium (LD) pruning and 4997 eGenes (FDR < 0.05). Melanocyte eQTLs differed considerably from those identified in the 44 GTEx tissue types, including skin. Over a third of melanocyte eGenes, including key genes in melanin synthesis pathways, were unique to melanocytes compared to those of GTEx skin tissues or TCGA melanomas. The melanocyte data set also identified trans-eQTLs, including those connecting a pigmentation-associated functional SNP with four genes, likely through cis-regulation of IRF4. Melanocyte eQTLs are enriched in cis-regulatory signatures found in melanocytes as well as in melanoma-associated variants identified through genome-wide association studies. Melanocyte eQTLs also colocalized with melanoma GWAS variants in five known loci. Finally, a transcriptome-wide association study using melanocyte eQTLs uncovered four novel susceptibility loci, where imputed expression levels of five genes (ZFP90, HEBP1, MSC, CBWD1, and RP11-383H13.1) were associated with melanoma at genome-wide significant P-values. Our data highlight the utility of lineage-specific eQTL resources for annotating GWAS findings, and present a robust database for genomic research of melanoma risk and melanocyte biology