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Migraine photophobia originating in cone-driven retinal pathways. - Brain : a journal of neurology
Migraine headache is uniquely exacerbated by light. Using psychophysical assessments in patients with normal eyesight we found that green light exacerbates migraine headache significantly less than white, blue, amber or red lights. To delineate mechanisms, we used electroretinography and visual evoked potential recording in patients, and multi-unit recording of dura- and light-sensitive thalamic neurons in rats to show that green activates cone-driven retinal pathways to a lesser extent than white, blue and red; that thalamic neurons are most responsive to blue and least responsive to green; and that cortical responses to green are significantly smaller than those generated by blue, amber and red lights. These findings suggest that patients' experience with colour and migraine photophobia could originate in cone-driven retinal pathways, fine-tuned in relay thalamic neurons outside the main visual pathway, and preserved by the cortex. Additionally, the findings provide substrate for the soothing effects of green light.Â© The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: firstname.lastname@example.org.
Association Between Menopausal Estrogen-Only Therapy and Ovarian Carcinoma Risk. - Obstetrics and gynecology
To describe the association between postmenopausal estrogen-only therapy use and risk of ovarian carcinoma, specifically with regard to disease histotype and duration and timing of use.We conducted a pooled analysis of 906 women with ovarian carcinoma and 1,220 women in a control group; all 2,126 women included reported having had a hysterectomy. Ten population-based case-control studies participating in the Ovarian Cancer Association Consortium, an international consortium whose goal is to combine data from many studies with similar methods so reliable assessments of risk factors can be determined, were included. Self-reported questionnaire data from each study were harmonized and conditional logistic regression was used to examine estrogen-only therapy's histotype-specific and duration and recency of use associations.Forty-three and a half percent of the women in the control group reported previous use of estrogen-only therapy. Compared with them, current or recent estrogen-only therapy use was associated with an increased risk for the serous (51.4%, odds ratio [OR] 1.63, 95% confidence interval [CI] 1.27-2.09) and endometrioid (48.6%, OR 2.00, 95% CI 1.17-3.41) histotypes. In addition, statistically significant trends in risk according to duration of use were seen among current or recent postmenopausal estrogen-only therapy users for both ovarian carcinoma histotypes (Ptrend<.001 for serous and endometrioid). Compared with women in the control group, current or recent users for 10 years or more had increased risks of serous ovarian carcinoma (36.8%, OR 1.73, 95% CI 1.26-2.38) and endometrioid ovarian carcinoma (34.9%, OR 4.03, 95% CI 1.91-8.49).We found evidence of an increased risk of serous and endometrioid ovarian carcinoma associated with postmenopausal estrogen-only therapy use, particularly of long duration. These findings emphasize that risk may be associated with extended estrogen-only therapy use.
Children's Attitudes Toward Peers With Unintelligible Speech Associated With Cleft Lip and/or Palate. - The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association
â€ƒ The objective of this study was to investigate whether reduced speech intelligibility in children with cleft palate affects social and personal attribute judgments made by typically developing children of different ages.â€ƒ The study (1) measured the correlation between intelligibility scores of speech samples from children with cleft palate and social and personal attribute judgments made by typically developing children based on these samples and (2) compared the attitude judgments made by children of different ages. Participants â€ƒ A total of 90 typically developing children, 30 in each of three age groups (7 to 8 years, 9 to 10 years, and 11 to 12 years).Speech intelligibility scores and typically developing children's attitudes were measured using eight social and personal attributes on a three-point rating scale.â€ƒ There was a significant correlation between the speech intelligibility scores and attitude judgments for a number of traits: "sick-healthy" as rated by the children aged 7 to 8 years, "no friends-friends" by the children aged 9 to 10 years, and "ugly-good looking" and "no friends-friends" by the children aged 11 to 12 years. Children aged 7 to 8 years gave significantly lower ratings for "mean-kind" but higher ratings for "shy-outgoing" when compared with the other two groups.â€ƒ Typically developing children tended to make negative social and personal attribute judgments about children with cleft palate based solely on the intelligibility of their speech. Society, educators, and health professionals should work together to ensure that children with cleft palate are not stigmatized by their peers.
The association between socioeconomic status and tumour stage at diagnosis of ovarian cancer: A pooled analysis of 18 case-control studies. - Cancer epidemiology
Socioeconomic status (SES) is a known predictor of survival for several cancers and it has been suggested that SES differences affecting tumour stage at diagnosis may be the most important explanatory factor for this. However, only a limited number of studies have investigated SES differences in tumour stage at diagnosis of ovarian cancer. In a pooled analysis, we investigated whether SES as represented by level of education is predictive for advanced tumour stage at diagnosis of ovarian cancer, overall and by histotype. The effect of cigarette smoking and body mass index (BMI) on the association was also evaluated.From 18 case-control studies, we obtained information on 10,601 women diagnosed with epithelial ovarian cancer. Study specific odds ratios (ORs) with corresponding 95% confidence intervals (CI) were obtained from logistic regression models and combined into a pooled odds ratio (pOR) using a random effects model.Overall, women who completed â‰¤high school had an increased risk of advanced tumour stage at diagnosis compared with women who completed >high school (pOR 1.15; 95% CI 1.03-1.28). The risk estimates for the different histotypes of ovarian cancer resembled that observed for ovarian cancers combined but did not reach statistical significance. Our results were unchanged when we included BMI and cigarette smoking.Lower level of education was associated with an increased risk of advanced tumour stage at diagnosis of ovarian cancer. The observed socioeconomic difference in stage at diagnosis of ovarian cancer calls for further studies on how to reduce this diagnostic delay.Copyright Â© 2016 Elsevier Ltd. All rights reserved.
Common Genetic Variation in Circadian Rhythm Genes and Risk of Epithelial Ovarian Cancer (EOC). - Journal of genetics and genome research
Disruption in circadian gene expression, whether due to genetic variation or environmental factors (e.g., light at night, shiftwork), is associated with increased incidence of breast, prostate, gastrointestinal and hematologic cancers and gliomas. Circadian genes are highly expressed in the ovaries where they regulate ovulation; circadian disruption is associated with several ovarian cancer risk factors (e.g., endometriosis). However, no studies have examined variation in germline circadian genes as predictors of ovarian cancer risk and invasiveness. The goal of the current study was to examine single nucleotide polymorphisms (SNPs) in circadian genes BMAL1, CRY2, CSNK1E, NPAS2, PER3, REV1 and TIMELESS and downstream transcription factors KLF10 and SENP3 as predictors of risk of epithelial ovarian cancer (EOC) and histopathologic subtypes. The study included a test set of 3,761 EOC cases and 2,722 controls and a validation set of 44,308 samples including 18,174 (10,316 serous) cases and 26,134 controls from 43 studies participating in the Ovarian Cancer Association Consortium (OCAC). Analysis of genotype data from 36 genotyped SNPs and 4600 imputed SNPs indicated that the most significant association was rs117104877 in BMAL1 (OR = 0.79, 95% CI = 0.68-0.90, p = 5.59 Ã— 10(-4)]. Functional analysis revealed a significant down regulation of BMAL1 expression following cMYC overexpression and increasing transformation in ovarian surface epithelial (OSE) cells as well as alternative splicing of BMAL1 exons in ovarian and granulosa cells. These results suggest that variation in circadian genes, and specifically BMAL1, may be associated with risk of ovarian cancer, likely through disruption of hormonal pathways.
Status Decreases Dominance in the West but Increases Dominance in the East. - Psychological science
In the experiments reported here, we integrated work on hierarchy, culture, and the enforcement of group cooperation by examining patterns of punishment. Studies in Western contexts have shown that having high status can temper acts of dominance, suggesting that high status may decrease punishment by the powerful. We predicted that high status would have the opposite effect in Asian cultures because vertical collectivism permits the use of dominance to reinforce the existing hierarchical order. Across two experiments, having high status decreased punishment by American participants but increased punishment by Chinese and Indian participants. Moreover, within each culture, the effect of status on punishment was mediated by feelings of being respected. A final experiment found differential effects of status on punishment imposed by Asian Americans depending on whether their Asian or American identity was activated. Analyzing enforcement through the lens of hierarchy and culture adds insight into the vexing puzzle of when and why people engage in punishment.Â© The Author(s) 2015.
Evidence of a genetic link between endometriosis and ovarian cancer. - Fertility and sterility
To evaluate whether endometriosis-associated genetic variation affects risk of ovarian cancer.Pooled genetic analysis.University hospital.Genetic data from 46,176 participants (15,361 ovarian cancer cases and 30,815 controls) from 41 ovarian cancer studies.None.Endometriosis-associated genetic variation and ovarian cancer.There was significant evidence of an association between endometriosis-related genetic variation and ovarian cancer risk, especially for the high-grade serous and clear cell histotypes. Overall we observed 15 significant burden statistics, which was three times more than expected.By focusing on candidate regions from a phenotype associated with ovarian cancer, we have shown a clear genetic link between endometriosis and ovarian cancer that warrants further follow-up. The functional significance of the identified regions and SNPs is presently uncertain, though future fine mapping and histotype-specific functional analyses may shed light on the etiologies of both gynecologic conditions.Copyright Â© 2016. Published by Elsevier Inc.
Electropalatography for Older Children and Adults with Residual Speech Errors. - Seminars in speech and language
Most residual speech errors (RSEs) involve abnormal positioning or movement of the tongue. However, it is not possible under normal circumstances to view directly the actions of the tongue during production of these distorted articulations. The visually inaccessible location of the tongue can often make precise diagnosis difficult in cases of RSEs, and intervention can be a particular challenge for clinicians when speech errors persist in older children and adults. Electropalatography (EPG) is a technique that can provide objective and clinically relevant data about details of tongue articulation during speech. Furthermore, biofeedback with EPG offers the possibility of an effective intervention for RSEs. This tutorial provides an overview of EPG and describes how the technique can contribute to our knowledge and treatment of abnormal tongue-palate contact in older children and adults with RSEs. An illustrative case study of a child with RSEs affecting fricatives and affricates is included.Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Common variants at the CHEK2 gene locus and risk of epithelial ovarian cancer. - Carcinogenesis
Genome-wide association studies have identified 20 genomic regions associated with risk of epithelial ovarian cancer (EOC), but many additional risk variants may exist. Here, we evaluated associations between common genetic variants [single nucleotide polymorphisms (SNPs) and indels] in DNA repair genes and EOC risk. We genotyped 2896 common variants at 143 gene loci in DNA samples from 15 397 patients with invasive EOC and controls. We found evidence of associations with EOC risk for variants at FANCA, EXO1, E2F4, E2F2, CREB5 and CHEK2 genes (P â‰¤ 0.001). The strongest risk association was for CHEK2 SNP rs17507066 with serous EOC (P = 4.74 x 10(-7)). Additional genotyping and imputation of genotypes from the 1000 genomes project identified a slightly more significant association for CHEK2 SNP rs6005807 (r (2) with rs17507066 = 0.84, odds ratio (OR) 1.17, 95% CI 1.11-1.24, P = 1.1Ã—10(-7)). We identified 293 variants in the region with likelihood ratios of less than 1:100 for representing the causal variant. Functional annotation identified 25 candidate SNPs that alter transcription factor binding sites within regulatory elements active in EOC precursor tissues. In The Cancer Genome Atlas dataset, CHEK2 gene expression was significantly higher in primary EOCs compared to normal fallopian tube tissues (P = 3.72Ã—10(-8)). We also identified an association between genotypes of the candidate causal SNP rs12166475 (r (2) = 0.99 with rs6005807) and CHEK2 expression (P = 2.70Ã—10(-8)). These data suggest that common variants at 22q12.1 are associated with risk of serous EOC and CHEK2 as a plausible target susceptibility gene.Â© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: email@example.com.
Epithelial-Mesenchymal Transition (EMT) Gene Variants and Epithelial Ovarian Cancer (EOC) Risk. - Genetic epidemiology
Epithelial-mesenchymal transition (EMT) is a process whereby epithelial cells assume mesenchymal characteristics to facilitate cancer metastasis. However, EMT also contributes to the initiation and development of primary tumors. Prior studies that explored the hypothesis that EMT gene variants contribute to epithelial ovarian carcinoma (EOC) risk have been based on small sample sizes and none have sought replication in an independent population. We screened 15,816 single-nucleotide polymorphisms (SNPs) in 296 genes in a discovery phase using data from a genome-wide association study of EOC among women of European ancestry (1,947 cases and 2,009 controls) and identified 793 variants in 278 EMT-related genes that were nominally (P < 0.05) associated with invasive EOC. These SNPs were then genotyped in a larger study of 14,525 invasive-cancer patients and 23,447 controls. A P-value <0.05 and a false discovery rate (FDR) <0.2 were considered statistically significant. In the larger dataset, GPC6/GPC5 rs17702471 was associated with the endometrioid subtype among Caucasians (odds ratio (OR) = 1.16, 95% CI = 1.07-1.25, P = 0.0003, FDR = 0.19), whereas F8 rs7053448 (OR = 1.69, 95% CI = 1.27-2.24, P = 0.0003, FDR = 0.12), F8 rs7058826 (OR = 1.69, 95% CI = 1.27-2.24, P = 0.0003, FDR = 0.12), and CAPN13 rs1983383 (OR = 0.79, 95% CI = 0.69-0.90, P = 0.0005, FDR = 0.12) were associated with combined invasive EOC among Asians. In silico functional analyses revealed that GPC6/GPC5 rs17702471 coincided with DNA regulatory elements. These results suggest that EMT gene variants do not appear to play a significant role in the susceptibility to EOC.Â© 2015 WILEY PERIODICALS, INC.
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