An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female anorectal dysfunction.

INTRODUCTION: The terminology for anorectal dysfunction in women has long been in need of a specific clinically-based Consensus Report. METHODS: This Report combines the input of members of the Standardization and Terminology Committees of two International Organizations, the International Urogynecological Association (IUGA) and the International Continence Society (ICS), assisted on Committee by experts in their fields to form a Joint IUGA/ICS Working Group on Female Anorectal Terminology. Appropriate core clinical categories and sub classifications were developed to give an alphanumeric coding to each definition. An extensive process of twenty rounds of internal and external review was developed to exhaustively examine each definition, with decision-making by collective opinion (consensus). RESULTS: A Terminology Report for anorectal dysfunction, encompassing over 130 separate definitions, has been developed. It is clinically based with the most common diagnoses defined. Clarity and user-friendliness have been key aims to make it interpretable by practitioners and trainees in all the different specialty groups involved in female pelvic floor dysfunction. Female-specific anorectal investigations and imaging (ultrasound, radiology and MRI) has been included whilst appropriate figures have been included to supplement and help clarify the text. Interval review (5-10 years) is anticipated to keep the document updated and as widely acceptable as possible. CONCLUSION: A consensus-based Terminology Report for female anorectal dysfunction terminology has been produced aimed at being a significant aid to clinical practice and a stimulus for research. Neurourol. Urodynam. 36:10-34, 2017. © 2016 Wiley Periodicals, Inc., and The International Urogynecological Association

Histone Deacetylases Regulate Gonadotropin-Releasing Hormone I Gene Expression via Modulating Otx2-Driven Transcriptional Activity

BACKGROUND: Precise coordination of the hypothalamic-pituitary-gonadal axis orchestrates the normal reproductive function. As a central regulator, the appropriate synthesis and secretion of gonadotropin-releasing hormone I (GnRH-I) from the hypothalamus is essential for the coordination. Recently, emerging evidence indicates that histone deacetylases (HDACs) play an important role in maintaining normal reproductive function. In this study, we identify the potential effects of HDACs on Gnrh1 gene transcription. METHODOLOGY/PRINCIPAL FINDINGS: Inhibition of HDACs activities by trichostatin A (TSA) and valproic acid (VPA) promptly and dramatically repressed transcription of Gnrh1 gene in the mouse immortalized mature GnRH neuronal cells GT1-7. The suppression was connected with a specific region of Gnrh1 gene promoter, which contains two consensus Otx2 binding sites. Otx2 has been known to activate the basal and also enhancer-driven transcription of Gnrh1 gene. The transcriptional activity of Otx2 is negatively modulated by Grg4, a member of the Groucho-related-gene (Grg) family. In the present study, the expression of Otx2 was downregulated by TSA and VPA in GT1-7 cells, accompanied with the opposite changes of Grg4 expression. Chromatin immunoprecipitation and electrophoretic mobility shift assays demonstrated that the DNA-binding activity of Otx2 to Gnrh1 gene was suppressed by TSA and VPA. Overexpression of Otx2 partly abolished the TSA- and VPA-induced downregulation of Gnrh1 gene expression. CONCLUSIONS/SIGNIFICANCE: Our data indicate that HDAC inhibitors downregulate Gnrh1 gene expression via repressing Otx2-driven transcriptional activity. This study should provide an insight for our understanding on the effects of HDACs in the reproductive system and suggests that HDACs could be potential novel targets for the therapy of GnRH-related diseases

The Lancet Breast Cancer Commission: tackling a global health, gender, and equity challenge

Breast cancer is an increasing global health, gender, socioeconomic, and equity challenge. In 2020, 2·3 million women were diagnosed with breast cancer and there were 685 000 deaths worldwide.1 Not only is breast cancer the highest incident cancer globally, but it is also the most prevalent, causing more disability-adjusted life-years lost than any other malignancy. Tackling breast cancer is a formidable task for health-care systems, policy makers, and other stakeholders. The numbers of people with metastatic breast cancer who go uncounted are concerning. Cancer registries record patients initially presenting with de-novo metastatic breast cancer, but data on those who develop metastases after a diagnosis of early breast cancer are scarce. In a world focused on breast cancer cure, these uncounted people living with metastatic disease face abandonment and stigma

Flexible target templates improve visual search accuracy for faces depicting emotion.

Theories of visual attention hypothesize that target selection depends upon matching visual inputs to a memory representation of the target - i.e., the target or attentional template. Most theories assume that the template contains a veridical copy of target features, but recent studies suggest that target representations may shift "off veridical" from actual target features to increase target-to-distractor distinctiveness. However, these studies have been limited to simple visual features (e.g., orientation, color), which leaves open the question of whether similar principles apply to complex stimuli, such as a face depicting an emotion, the perception of which is known to be shaped by conceptual knowledge. In three studies, we find confirmatory evidence for the hypothesis that attention modulates the representation of an emotional face to increase target-to-distractor distinctiveness. This occurs over-and-above strong pre-existing conceptual and perceptual biases in the representation of individual faces. The results are consistent with the view that visual search accuracy is determined by the representational distance between the target template in memory and distractor information in the environment, not the veridical target and distractor features