Citations

Though the public consciousness is typically focused on factors such as psychology, penis size, and the presence of the “G‐spot,” there are other anatomical and neuro‐anatomic differences that could play an equal, or more important, role in the frequency and intensity of orgasms. Discovering these variations could direct further medical or procedural management to improve sexual satisfaction. The aim of this study is to review the available literature of anatomical sexual variation and to explain why this variation may predispose some patients toward a particular sexual experience. In this review, we explored the available literature on sexual anatomy and neuro‐anatomy. We used PubMed and OVID Medline for search terms, including orgasm, penile size variation, clitoral variation, Grafenberg spot, and benefits of orgasm. First we review the basic anatomy and innervation of the reproductive organs. Then we describe several anatomical variations that likely play a superior role to popular known variation (penis size, presence of g‐spot, etc). For males, the delicate play between the parasympathetic and sympathetic nervous systems is vital to achieve orgasm. For females, the autonomic component is more complex. The clitoris is the primary anatomical feature for female orgasm, including its migration toward the anterior vaginal wall. In conclusions, orgasms are complex phenomena involving psychological, physiological, and anatomic variation. While these variations predispose people to certain sexual function, future research should explore how to surgically or medically alter these. Clin. Anat. 29:665–672, 2016. © 2016 Wiley Periodicals, Inc.

The use of programmed cell death 1 ligand 1 (PD‐L1) as a predictive biomarker to select patients to receive programmed cell death 1 (PD‐1) or PD‐L1 inhibitors in non‐small cell lung cancer (NSCLC) is limited by the definitions of positivity, interassay agreement, and intra‐ and intertumoral heterogeneity of expression. Although PD‐L1 expression enriches for responses, the lack of expression does not exclude clinical benefit.

Postmenopausal women with nonalcoholic steatohepatitis are at an increased risk of hepatic fibrosis compared with premenopausal women. Whether duration of estrogen deficiency in postmenopausal state dictates an individual's fibrosis risk remains uninvestigated. We assessed the associations of age at menopause and time from menopause with fibrosis severity in postmenopausal women with nonalcoholic fatty liver disease. Data from 488 postmenopausal women with (1) histologic diagnosis of nonalcoholic fatty liver disease and (2) self‐reported information on age at menopause were analyzed. The associations of premature menopause (age at menopause of <40 years) and time from menopause (age at study enrollment ‐ age at menopause, years) with fibrosis severity (stage 0‐4) were assessed using multiple ordinal logistic regression models with and without adjusting for clinical confounders. Among the participants (age at menopause 43.7 ± 8.6 years), women with premature menopause (29.3%) were younger at enrollment ( P < 0.001) and used hormone replacement therapy more often ( P < 0.003). After adjusting for age at enrollment, race, waist circumference standardized by body mass index, current smoking, current alcohol use, hypertension, diabetes/impaired fasting glucose, homeostatic model assessment of insulin resistance, and hormone replacement therapy, premature menopause was associated with an increased likelihood of having more severe fibrosis (adjusted cumulative odds ratio = 1.9, 95% confidence interval 1.3‐2.7, P = 0.001), while time from menopause was directly associated with an increased likelihood of having more severe fibrosis (adjusted cumulative odds ratio for 5‐year unit = 1.2, 95% confidence interval 1.1‐1.3, P = 0.002). Conclusion : Duration of estrogen deficiency in postmenopausal state confers fibrosis risk among postmenopausal women with nonalcoholic fatty liver disease. (H epatology 2016;64:85–91)

Summary The transcription factor forkhead box protein A1 (FOXA1) plays a critical role in the proliferation of human breast cancer cells, particularly estrogen receptor alpha (ERα)‐positive luminal breast cancer cells. However, genetic studies of the requirement for Foxa1 in mammary tumor formation in mice have been hampered by the lack of a conditional gene ablation. We examined three mouse models of mammary‐specific ablation of Foxa1 in ductal epithelial cells to identify the best system for complete and mammary‐specific ablation of Foxa1. We found that MMTV‐Cre and MMTV‐rtTA;Tet‐On‐Cre led to partial deletion of Foxa1 and attenuated mammary duct formation, whereas Krt14‐Cre led to complete ablation of Foxa1 and abolished mammary duct formation, in Foxa1 loxP/loxP mice. These results demonstrate that Foxa1 is essential for mammary duct formation, and reveal a series of mouse models in which mammary expression of Foxa1 can be attenuated or completely blocked. Our study also suggests a potentially powerful model for complete ablation of Foxa1 in mammary epithelial cells using Krt14‐driven Cre expression in an inducible manner, such as Krt14‐rtTA;Tet‐On‐Cre . This model system will facilitate further in vivo functional studies of Foxa1 or other factors in mammary gland development and tumor formation and progression. genesis 54:277–285, 2016. © 2016 Wiley Periodicals, Inc.

Background— Whether knowledge of genetic risk for coronary heart disease (CHD) affects health-related outcomes is unknown. We investigated whether incorporating a genetic risk score (GRS) in CHD risk estimates lowers low-density lipoprotein cholesterol (LDL-C) levels. Methods and Results— Participants (n=203, 45–65 years of age, at intermediate risk for CHD, and not on statins) were randomly assigned to receive their 10-year probability of CHD based either on a conventional risk score (CRS) or CRS + GRS ( + GRS). Participants in the + GRS group were stratified as having high or average/low GRS. Risk was disclosed by a genetic counselor followed by shared decision making regarding statin therapy with a physician. We compared the primary end point of LDL-C levels at 6 months and assessed whether any differences were attributable to changes in dietary fat intake, physical activity levels, or statin use. Participants (mean age, 59.4±5 years; 48% men; mean 10-year CHD risk, 8.5±4.1%) were allocated to receive either CRS (n=100) or + GRS (n=103). At the end of the study period, the + GRS group had a lower LDL-C than the CRS group (96.5±32.7 versus 105.9±33.3 mg/dL; P =0.04). Participants with high GRS had lower LDL-C levels (92.3±32.9 mg/dL) than CRS participants ( P =0.02) but not participants with low GRS (100.9±32.2 mg/dL; P =0.18). Statins were initiated more often in the + GRS group than in the CRS group (39% versus 22%, P <0.01). No significant differences in dietary fat intake and physical activity levels were noted. Conclusions— Disclosure of CHD risk estimates that incorporated genetic risk information led to lower LDL-C levels than disclosure of CHD risk based on conventional risk factors alone. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01936675.