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Up to a quarter of ovarian masses originate from germ cells, and many of these are mature cystic teratomas. The secondary development of malignancy is a rare but well-known phenomenon in patients with ovarian teratomas. Squamous-cell carcinoma accounts for 80% of secondary malignant transformations of ovarian teratomas. We aimed to do an up-to-date systematic review of this rare malignant transformation. 64 suitable studies provided information on 277 patients. Squamous-cell carcinoma in mature cystic teratoma was mainly found in women aged more than 50 years, with high concentrations of squamous-cell-carcinoma antigen and cancer antigen CA125, and with ovarian tumours more than 100 mm in size. Patients with FIGO stage Ia tumours had better survival than those with more advanced disease. Complete resection together with hysterectomy, bilateral salpingo-oophorectomy and lymphadenectomy for patients with advanced disease, followed by adjuvant chemotherapy with an alkylating drug was associated with higher survival, radiotherapy was not. We make proposals for investigation and treatment of this rare disorder. [ABSTRACT FROM AUTHOR]

Objective: To assess national-level trends, characteristics, and outcomes of pregnancies with Turner syndrome in the United States., Design: Cross-sectional study., Setting: The Healthcare Cost and Utilization Project's National Inpatient Sample., Subjects: A total of 17,865,495 hospital deliveries from 2016-2020., Exposure: A diagnosis of Turner syndrome, identified according to the World Health Organization's International Classification of Disease 10th revision code of Q96., Main Outcome Measures: Obstetrics outcomes related to Turner syndrome, assessed with inverse probability of treatment weighting cohort and multivariable binary logistic regression modeling., Results: The prevalence of pregnant patients with Turner syndrome was 7.0 per 100,000 deliveries (one in 14,235). The number of hospital deliveries with patients who have a diagnosis of Turner syndrome increased from 5.0 to 11.7 per 100,000 deliveries during the study period (adjusted-odds ratio [aOR] for 2020 vs. 2016; 2.18, 95% confidence interval [CI] 1.83-2.60). Pregnant patients with Turner syndrome were more likely to have a diagnosis of pregestational hypertension (4.8% vs. 2.8%; aOR 1.65; 95% CI 1.26-2.15), uterine anomaly (1.6% vs. 0.4%; aOR, 3.01; 95% CI 1.93-4.69), and prior pregnancy losses (1.6% vs. 0.3%; aOR 4.70; 95% CI 3.01-7.32) compared with those without Turner syndrome. For the index obstetric characteristics, Turner syndrome was associated with an increased risk of intrauterine fetal demise (10.9% vs. 0.7%; aOR 8.40; 95% CI 5.30-13.30), intrauterine growth restriction (8.5% vs. 3.5%; aOR 2.11; 95% CI 1.48-2.99), and placenta accreta spectrum (aOR 3.63; 95% CI 1.20-10.97). For delivery outcome, pregnant patients with Turner syndrome were more likely to undergo cesarean delivery (41.6% vs. 32.3%; aOR 1.53; 95% CI 1.26-1.87). Moreover, the odds of periviable delivery (22-25 weeks: 6.1% vs. 0.4%; aOR 5.88; 95% CI 3.47-9.98) and previable delivery (<22 weeks: 3.3% vs. 0.3%; aOR 2.87; 95% CI 1.45-5.69) were increased compared with those without Turner syndrome., Conclusions: The results of contemporaneous, nationwide assessment in the United States suggest that although pregnancy with Turner syndrome is uncommon this may represent a high-risk group, particularly for intrauterine fetal demise and periviable delivery. Establishing a society-based approach for preconception counseling and antenatal follow-up would be clinically compelling., Competing Interests: Declaration of Interests Z.S.A. has nothing to disclose. A.D.M. has nothing to disclose. L.S.A. has nothing to disclose. R.S.M. has nothing to disclose. K.V.E. has nothing to disclose. S.M. received research funding from Merck. D.B. has nothing to disclose. R.J.P. has nothing to disclose. J.G.O. has nothing to disclose. K.M. has nothing to disclose., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The prevalence of musculoskeletal disorders is high in oral and maxillofacial surgeons (OS) due to their static and contorted working positions. Hence, the aim of this study was to conduct posture analyses in this specific group of dental professionals using the Rapid Upper Limb Assessment (RULA)., Methods: In total, 15 (12 m/3 f) OS participated in this study. An inertial motion capture system (Xsens) was used to collect kinematic data during a simulated workflow. Computer-based routines calculated the RULA score for the extracted joint angles at each defined time point. Then, an analysis of the time-dependent RULA scores by body regions was conducted. Key variables were the relative occurrence of specific RULA scores during the complete workflow, individual subtasks, and for treatment of each of the four different dental quadrants. The subtasks and dental quadrants were compared using the Friedman test., Results: The total median RULA score represented a high risk for OS during their work (7), including the temporal component (OS spent 77.54% of their working time with a RULA score of 7). The wrists and hands, elbows, lower arms, and the neck were exposed to postures with the highest risk for musculoskeletal strain., Discussion: For OS, both the right and the left assisting hand were heavily strained while working on the first dental quadrant caused the most unfavorable postures for OS., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Although intrauterine devices provide effective contraceptive protection, unintentional pregnancy can occur. Previous studies have shown that a retained intrauterine device during pregnancy is associated with adverse pregnancy outcomes but there is a paucity of nationwide data and analysis., Objective: This study aimed to describe characteristics and outcomes of pregnancies with a retained intrauterine device., Study Design: This serial cross-sectional study used data from the Healthcare Cost and Utilization Project's National Inpatient Sample. The study population comprised 18,067,310 hospital deliveries for national estimates from January 2016 to December 2020. The exposure was retained intrauterine device status, identified by the World Health Organization's International Classification of Diseases, Tenth Revision, code O26.3. The co-primary outcome measures were incidence rate, clinical and pregnancy characteristics, and delivery outcome of patients with a retained intrauterine device. To assess the pregnancy characteristics and delivery outcomes, an inverse probability of treatment weighting cohort was created to mitigate the prepregnant confounders for a retain intrauterine device., Results: A retained intrauterine device was reported in 1 in 8307 hospital deliveries (12.0 per 100,000). In a multivariable analysis, Hispanic individuals, grand multiparity, obesity, alcohol use, and a previous uterine scar were patient characteristics associated with a retained intrauterine device (all P<.05). Current pregnancy characteristics associated with a retained intrauterine device included preterm premature rupture of membrane (9.2% vs 2.7%; adjusted odds ratio, 3.15; 95% confidence interval, 2.41-4.12), fetal malpresentation (10.9% vs 7.2%; adjusted odds ratio, 1.47; 95% confidence interval, 1.15-1.88), fetal anomaly (2.2% vs 1.1%; adjusted odds ratio, 1.71; 95% confidence interval, 1.03-2.85), intrauterine fetal demise (2.6% vs 0.8%; adjusted odds ratio, 2.21; 95% confidence interval, 1.37-3.57), placenta malformation (1.8% vs 0.8%; adjusted odds ratio, 2.12; 95% confidence interval, 1.20-3.76), placenta abruption (4.7% vs 1.1%; adjusted odds ratio, 3.24; 95% confidence interval, 2.25-4.66), and placenta accreta spectrum (0.7% vs 0.1%; adjusted odds ratio, 4.82; 95% confidence interval, 1.99-11.65). Delivery characteristics associated with a retained intrauterine device included previable loss at <22 weeks' gestation (3.4% vs 0.3%; adjusted odds ratio, 5.49; 95% confidence interval, 3.30-9.15) and periviable delivery at 22 to 25 weeks' gestation (3.1% vs 0.5%; adjusted odds ratio, 2.81; 95% confidence interval, 1.63-4.86). Patients in the retained intrauterine device group were more likely to have a diagnosis of retained placenta at delivery (2.5% vs 0.4%; adjusted odds ratio, 4.45; 95% confidence interval, 2.70-7.36) and to undergo manual placental removal (3.2% vs 0.6%; adjusted odds ratio, 4.81; 95% confidence interval, 3.11-7.44)., Conclusion: This nationwide analysis confirmed that pregnancy with a retained intrauterine device is uncommon, but these pregnancies may be associated with high-risk pregnancy characteristics and outcomes., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The Rapid Upper Limb Assessment (RULA) is used for the risk assessment of workplace-related activities. Thus far, the paper and pen method (RULA-PP) has been predominantly used for this purpose. In the present study, this method was compared with an RULA evaluation based on kinematic data using inertial measurement units (RULA-IMU). The aim of this study was, on the one hand, to work out the differences between these two measurement methods and, on the other, to make recommendations for the future use of the respective method on the basis of the available findings., Methods: For this purpose, 130 (dentists + dental assistants, paired as teams) subjects from the dental profession were photographed in an initial situation of dental treatment and simultaneously recorded with the IMU system (Xsens). In order to compare both methods statistically, the median value of the difference of both methods, the weighted Cohen's Kappa, and the agreement chart (mosaic plot) were applied., Results: In Arm and Wrist Analysis-area A -here were differences in risk scores; here, the median difference was 1, and the agreement in the weighted Cohen's kappa test also remained between 0.07 and 0.16 (no agreement to poor agreement). In area B-Neck, Trunk, and Leg Analysis -the median difference was 0, with at least one poor agreement in the Cohen's Kappa test of 0.23-0.39. The final score has a median of 0 and a Cohen's Kappa value of 0.21-0.28. In the mosaic plot, it can be seen that RULA-IMU had a higher discriminatory power overall and more often reached a value of 7 than RULA-PP., Conclusion: The results indicate a systematic difference between the methods. Thus, in the RULA risk assessment, RULA-IMU is mostly one assessment point above RULA-PP. Therefore, future study results of RULA by RULA-IMU can be compared with literature results obtained by RULA-PP to further improve the risk assessment of musculoskeletal diseases.

Musculoskeletal disorder (MSD) is already prevalent in dental students despite their young age and the short duration of dental practice. The current findings state that the causes of MSD are related to posture during dental work. This study aims to investigate the ergonomic risk of dental students. In order to analyze the ergonomic risk of dental students, 3D motion analyses were performed with inertial sensors during the performance of standardized dental activities. For this purpose, 15 dental students and 15 dental assistant trainees (all right-handed) were measured in a team. Data were analyzed using the Rapid Upper Limb Assessment (RULA), which was modified to evaluate objective data. Ergonomic risk was found for the following body parts in descending order: left wrist, right wrist, neck, trunk, left lower arm, right lower arm, right upper arm, left upper arm. All relevant body parts, taken together, exhibited a posture with the highest RULA score that could be achieved (median Final Overall = 7), with body parts in the very highest RULA score of 7 for almost 80% of the treatment time. Dental students work with poor posture over a long period of time, exposing them to high ergonomic risk. Therefore, it seems necessary that more attention should be paid to theoretical and practical ergonomics in dental school.

When the inventory is arranged in a dental practice, a distinction can be made between four different dental workplace concepts (DWCs). Since the prevalence of musculoskeletal diseases in dental professionals is very high, preventive solution need to be investigated. As the conventionally used DWCs have, to date, never been studied in terms of their ergonomics, this study aims to investigate the ergonomic risk when working at the four different DWCs. In total, 75 dentists (37 m/38 f) and 75 dental assistants (16 m/59 f) volunteered to take part in this study. Standardized cooperative working procedures were carried out in a laboratory setting and kinematic data were recorded using an inertial motion capture system. The data were applied to an automated version of the Rapid Upper Limb Assessment (RULA). Comparisons between the DWCs and between the dentists and dental assistants were calculated. In all four DWCs, both dentists and dental assistants spent 95-97% of their working time in the worst possible RULA score. In the trunk, DWCs 1 and 2 were slightly favorable for both dentists and dental assistants, while for the neck, DWC 4 showed a lower risk score for dentists. The ergonomic risk was extremely high in all four DWCs, while only slight advantages for distinct body parts were found. The working posture seemed to be determined by the task itself rather than by the different inventory arrangements.

Traditional ergonomic risk assessment tools such as the Rapid Upper Limb Assessment (RULA) are often not sensitive enough to evaluate well-optimized work routines. An implementation of kinematic data captured by inertial sensors is applied to compare two work routines in dentistry. The surgical dental treatment was performed in two different conditions, which were recorded by means of inertial sensors (Xsens MVN Link). For this purpose, 15 (12 males/3 females) oral and maxillofacial surgeons took part in the study. Data were post processed with costume written MATLAB ® routines, including a full implementation of RULA (slightly adjusted to dentistry). For an in-depth comparison, five newly introduced levels of complexity of the RULA analysis were applied, i.e., from lowest complexity to highest: (1) RULA score, (2) relative RULA score distribution, (3) RULA steps score, (4) relative RULA steps score occurrence, and (5) relative angle distribution. With increasing complexity, the number of variables times (the number of resolvable units per variable) increased. In our example, only significant differences between the treatment concepts were observed at levels that are more complex: the relative RULA step score occurrence and the relative angle distribution (level 4 + 5). With the presented approach, an objective and detailed ergonomic analysis is possible. The data-driven approach adds significant additional context to the RULA score evaluation. The presented method captures data, evaluates the full task cycle, and allows different levels of analysis. These points are a clear benefit to a standard, manual assessment of one main body position during a working task.

Background: Dentists are at a higher risk of suffering from musculoskeletal disorders (MSD) than the general population. However, the latest study investigating MSD in the dental profession in Germany was published about 20 years ago. Therefore, the aim of this study was to reveal the current prevalence of MSD in dentists and dental students in Germany., Methods: The final study size contained 450 (287 f/163 m) subjects of different areas of specialization. The age of the participants ranged from 23 to 75 years. The questionnaire consisted of a modified version of the Nordic Questionnaire, work-related questions from the latest questionnaire of German dentists, typical medical conditions and self-developed questions., Results: The overall prevalence showed that dentists suffered frequently from MSD (seven days: 65.6%, twelve months: 92%, lifetime: 95.8%). The most affected body regions included the neck (42.7%-70.9%-78.4%), shoulders (29.8%-55.6%-66.2%) and lower back (22.9%-45.8%-58.7%). Overall, female participants stated that they suffered from pain significantly more frequently, especially in the neck, shoulders and upper back., Conclusion: The prevalence of MSD among dentists, especially in the neck, shoulder and back area, was significantly higher than in the general population. In addition, women suffered more frequently from MSD than men in almost all body regions.

Background: Dental professionals are subjected to higher risks for musculoskeletal disorders (MSDs) than other professional groups, especially the hand region. This study aims to investigate the prevalence of hand complaints among dentists (Ds) and dental assistants (DAs) and examines applied therapies., Methods: For this purpose, an online questionnaire analysed 389 Ds (240female/149male) and 406 DAs (401female/5male) working in Germany. The self-reported data of the two occupational groups were compared with regard to the topics examined. The questionnaire was based on the Nordic Questionnaire (self-reported lifetime, 12-month and 7-day MSDs prevalence of the hand, the conducted therapy and its success), additional occupational and sociodemographic questions as well as questions about specific medical conditions., Results: 30.8% of Ds affirmed MSDs in the hand at any time in their lives, 20.3% in the last twelve months and 9.5% in the last seven days. Among DAs, 42.6% reported a prevalence of MSDs in the hand at any time in their lives, 31.8% in the last 12 months and 15.3% in the last seven days. 37.5% of the Ds and 28.3% of the DAs stated that they had certain treatments. For both, Ds and DAs, physiotherapy was the most frequently chosen form of therapy. 89.7% of Ds and 63.3% of DAs who received therapy reported an improvement of MSDs., Conclusion: Although the prevalence of MSDs on the hand is higher among DAs than among Ds, the use of therapeutic options and the success of therapy is lower for DAs compared to Ds., Competing Interests: The authors have declared that no competing interests exist.

Background: The present study aims to elucidate the state of gender equality in high-quality research by analyzing the representation of female authorships in the last decade (from 2008 to 2016)., Methods: Based on the Gendermetrics platform, 293,557 research articles from 54 journals listed in the Nature Index were considered covering the categories Life Science, Multidisciplinary, Earth & Environmental and Chemistry. The core method was the combined analysis of the proportion of female authorships and the female-to-male odds ratio for first, co- and last authorships. The distribution of prestigious authorships was measured by the Prestige Index., Results: 29.8% of all authorships and 33.1% of the first, 31.8% of the co- and 18.1% of the last authorships were held by women. The corresponding female-to-male odds ratio is 1.19 (CI: 1.18-1.20) for first, 1.35 (CI: 1.34-1.36) for co- and 0.47 (CI: 0.46-0.48) for last authorships. Women are underrepresented at prestigious authorships compared to men (Prestige Index = -0.42). The underrepresentation accentuates in highly competitive articles attracting the highest citation rates, namely, articles with many authors and articles that were published in highest-impact journals. More specifically, a large negative correlation between the 5-Year-Impact-Factor of a journal and the female representation at prestigious authorships was revealed (r(52) = -.63, P < .001). Women publish fewer articles compared to men (39.0% female authors are responsible for 29.8% of all authorships) and are underrepresented at productivity levels of more than 2 articles per author. Articles with female key authors are less frequently cited than articles with male key authors. The gender-specific differences in citation rates increase the more authors contribute to an article. Distinct differences at the journal, journal category, continent and country level were revealed. The prognosis for the next decades forecast a very slow harmonization of authorships odds between the two genders.

Endometriosis is a common female reproductive disease characterized by invasion of endometrial cells into other organs, frequently causing pelvic pain and infertility. Alterations of the vitamin D system have been linked to endometriosis incidence and severity. To shed light on the potential mechanism for these associations, we examined the effects of 1,25(OH) 2 D 3 on gene expression in endometriosis cells. Stromal cell lines derived from endometriosis tissue were treated with 1,25(OH) 2 D 3 , and RNA-seq was used to identify genes differentially expressed between treated and untreated cells. Gene ontology and pathway analyses were carried out using Partek Flow and Ingenuity software suites, respectively. We identified 1627 genes that were differentially expressed (886 down-regulated and 741 up-regulated) by 1,25(OH) 2 D 3 . Only one gene, CYP24A1, was strongly up-regulated (369-fold). Many genes were strongly down-regulated. 1,25(OH) 2 D 3 treatment down-regulated several genetic pathways related to neuroangiogenesis, cellular motility, and invasion, including pathways for axonal guidance, Rho GDP signaling, and matrix metalloprotease inhibition. These findings support a role for vitamin D in the pathophysiology of endometriosis, and provide new targets for investigation into possible causes and treatments., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Geographical variation of the general practitioner (GP) workforce is known between rural and urban areas. However, data about the variation between and within urban areas are lacking., Method: We analyzed distribution patterns of GP full time equivalents (FTE) in German cities with a population size of more than 500,000. We correlated their distribution with area measures of social deprivation in order to analyze preferences within neighborhood characteristics. For this purpose, we developed two area measures of deprivation: Geodemographic Index (GDI) and Cultureeconomic Index (CEI)., Results: In total n = 9034.75 FTE were included in n = 14 cities with n = 171 districts. FTE were distributed equally on inter-city level (mean: 6.49; range: 5.12-7.20; SD: 0.51). However, on intra-city level, GP distribution was skewed (mean: 6.54; range: 1.80-43.98; SD: 3.62). Distribution patterns of FTE per 10^4 residents were significantly correlated with GDI (r = -0.49; p < 0.001) and CEI (r = -0.22; p = 0.005). Therefore, location choices of GPs were mainly positively correlated with 1) central location (r = -0.50; p < 0.001), 2) small household size of population (r = -0.50; p < 0.001) and 3) population density (r = 0.35; p < 0.001)., Conclusion: Intra-city distribution of GPs was skewed, which could affect the equality of access for the urban population. Furthermore, health services planners should be aware of GP location preferences. This could be helpful to better understand and plan delivery of health services. Within this process the presented Geodemographic Index (GDI) could be of use.

Purpose: In the field of gynecology and obstetrics, studies exploring the workplace situation are important. We conducted this study with the overall aim to assess the subjective perception of working conditions of OB/GYNs in German hospitals. Since gender ratios are changing among German physicians in general and among OB/GYNs in particular, a special focus was put on gender-based differences., Methods: This study uses data from the iCEPT Study (n = 7090). From this database, data from physicians working in the field of gynecology and obstetrics (n = 381) were analyzed. The iCEPT questionnaire was based upon established questionnaires., Results: 92.1 % (95 % CI 89.2-95.3) of respondents stated to be often under time pressure and 89.8 % (95 % CI 87.6-93.3) stated frequent disturbances during work time. Women felt significantly more often under time pressure than men (OR = 2.73; 95 % CI 1.25-5.92; p = 0.009). Moreover, only about every third respondent stated to be in control of his or her work. Feedback about their work was received by 27.6 % (95 % CI 23.4-32.1) of respondents. However, male physicians got significantly more often feedback with an odds ratio of OR = 2.03 (95 % CI 1.21-3.41; p = 0.007). In regard to job satisfaction, about one in two (55.1 %; 95 % CI 50.4-60.2) stated to be satisfied with his or her job. However, men seemed more often satisfied than women with an OR = 1.98 (95 % CI 1.18-3.32; p = 0.009). No significant gender difference was seen in the analysis of the social climate and the social support., Conclusions: It is important to be aware of the documented gender differences regarding perception of working conditions. In order to sustain the gender diversity in the specialty of OB/GYNs these differences should be resolved. Special attention should be drawn to the improvement of job demands and control of employees.

Although vaccination against the Human Papilloma Virus (HPV) reduces the risk of related morbidities, the vaccine uptake remains low in adolescents. This has been attributed to limited parental knowledge and misconceptions. In this cross sectional study, we assessed the (1) clarity of educational material informing Hispanic mothers about HPV, cervical cancer and the HPV vaccine, (2) determined vaccination acceptability and (3) identified predictors of vaccine acceptance in an underserved health setting. 418 Hispanic mothers received the educational material and completed an anonymous survey. 91 % of participants understood most or all of the information provided. 77 % of participants reported vaccine acceptance for their children; this increased to 84 % when only those with children eligible to receive vaccination were included. Significant positive predictors of maternal acceptance of the HPV vaccine for their children were understanding most or all of the provided information, older age and acceptance of the HPV vaccine for themselves. Concerns about safety and general dislike of vaccines were negatively associated with HPV vaccine acceptance. Prior knowledge, level of education, previous relevant gynecologic history, general willingness to vaccinate and other general beliefs about vaccines were not significantly associated with HPV vaccine acceptance. The majority of participants reported understanding of the provided educational material. Vaccine acceptability was fairly high, but was even higher among those who understood the information. This study documents a cost-effective way to provide Hispanic mothers with easy-to-understand HPV-related information that could increase parental vaccine acceptability and future vaccine uptake among their children.

Background: Tuberculosis belongs to the lung infectious diseases with the highest impact on global burden of disease. Yet there is no concise scientometric study about tuberculosis research. Therefore, the NewQiS project elected this subject as focus of an in depth analysis to perform density equalizing mapping in combination with scientometrics., Method: In this retrospective study all publications related to tuberculosis research listed in the Web of Science database between 1900 and 2012 were identified, analyzed and submitted to density equalizing mapping procedures., Results: In total 58,319 entries on TBC were identified with the USA being the most productive country with 11,788 publications, followed by the United Kingdom (4202), India (3456), France (2541), South Africa (1840), Germany (1747) and China (1427). Concerning the citations rate Denmark leads with 43.7 citations per article, followed by Latvia (39.1), Gambia (38.3), Senegal (34.9), and the Netherlands (31.4). Chart techniques demonstrates a widely ramified international network with a focus the joint work of USA, the UK and South Africa., Conclusions: This is the first density equalizing and scientometric study that addresses tuberculosis research over a period of 112 years. It illustrates global tuberculosis research architecture and stresses the need for strengthening global research efforts and funding program., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Endometriosis is a common condition that is associated with an increased risk of developing ovarian carcinoma. Improved in vitro models of this disease are needed to better understand how endometriosis, a benign disease, can undergo neoplastic transformation, and for the development of novel treatment strategies to prevent this progression., Methods: We describe the generation and in vitro characterization of novel TERT immortalized ovarian endometriosis epithelial cell lines (EEC16-TERT)., Results: Expression of TERT alone was sufficient to immortalize endometriosis epithelial cells. TERT immortalization induces an epithelial-to-mesenchymal transition and perturbation in the expression of genes involved in the development of ovarian cancer. EEC16-TERT was non-tumorigenic when xenografted into immunocompromised mice but grew in anchorage-independent growth assays in an epidermal growth factor and hydrocortisone dependent manner. Colony formation in agar was abolished by inhibition of Src, and the Src pathway was found to be activated in human endometriosis lesions., Conclusions: This new in vitro model system mimics endometriosis and the early stages of neoplastic transformation in the development of endometriosis associated ovarian cancer. We demonstrate the potential clinical relevance of this model by identifying Src activation as a novel pathway in endometriosis that could be targeted therapeutically, perhaps as a novel strategy to manage endometriosis clinically, or to prevent the development of endometriosis-associated ovarian cancer., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Endometriosis is characterized by the presence of functional endometrial tissue outside of the uterine cavity. It affects 1 in 10 women of reproductive age. This chronic condition commonly leads to consequences such as pelvic pain, dysmenorrhea, infertility and an elevated risk of epithelial ovarian cancer. Despite the prevalence of endometriosis and its impact on women's lives, there are relatively few in vitro and in vivo models available for studying the complex disease biology, pathophysiology, and for use in the preclinical development of novel therapies. The goal of this study was to develop a novel three-dimensional (3D) cell culture model of ovarian endometriosis and to test whether it is more reflective of endometriosis biology than traditional two dimensional (2D) monolayer cultures., Methods: A novel ovarian endometriosis epithelial cell line (EEC16) was isolated from a 34-year old female with severe endometriosis. After characterization of cells using in vitro assays, western blotting and RNA-sequencing, this cell line and a second, already well characterized endometriosis cell line, EEC12Z, were established as in vitro 3D spheroid models. We compared biological features of 3D spheroids to 2D cultures and human endometriosis lesions using immunohistochemistry and real-time semi-quantitative PCR., Results: In comparison to normal ovarian epithelial cells, EEC16 displayed features of neoplastic transformation in in vitro assays. When cultured in 3D, EEC16 and EEC12Z showed differential expression of endometriosis-associated genes compared to 2D monolayer cultures, and more closely mimicked the molecular and histological features of human endometriosis lesions., Conclusions: To our knowledge, this represents the first report of an in vitro spheroid model of endometriosis. 3D endometriosis models represent valuable experimental tools for studying EEC biology and the development of novel therapeutic approaches.

Optimal care for breast cancer patients undergoing aromatase inhibitor (AI) treatment is ensured when estradiol (E2) levels are adequately suppressed. To assess treatment efficacy accurately, it is important to measure the serum E2 levels using a well validated assay method with high sensitivity and specificity. This translates into the urgent need to evaluate various E2 immunoassay kits, which are frequently used in hospital settings to measure E2 serum levels in patients undergoing AI treatment, so clinicians obtain accurate and reliable measurements allowing appropriate clinical decision making. Our objective was to evaluate the performance of different commercially available and commonly used E2 immunoassay kits regarding measurement of E2 levels in the serum of postmenopausal breast cancer patients treated with AIs, in comparison to a highly accurate and reliable mass spectrometry assay. Clinical and demographic data were obtained from 77 postmenopausal breast cancer patients who were treated with an AI. Serum E2 levels were measured by 6 immunoassay methods and by liquid chromatography-tandem mass spectrometry (LC-MS/MS), which served as the standard for comparison. Analysis of E2 by LC-MS/MS showed that 70% of the samples had levels that were <5 pg/ml. Three of the assays carried out with commercial E2 immunoassay kits had poor sensitivities and were not able to detect E2 levels <10 or <20 pg/ml. Although two of the E2 assays using commercial kits demonstrated a better sensitivity (5 pg/ml), the measured E2 values were substantially higher than those obtained by LC-MS/MS. The assay with the sixth commercial E2 kit grossly underestimated the true E2 values. E2 assays carried out with commercial E2 immunoassay kits lack the accuracy to measure the very low serum E2 levels found in patients being treated with AIs. Serum samples from such patients should be sent to laboratories that use a mass spectrometry assay.

HNF1B is overexpressed in clear cell epithelial ovarian cancer, and we observed epigenetic silencing in serous epithelial ovarian cancer, leading us to hypothesize that variation in this gene differentially associates with epithelial ovarian cancer risk according to histological subtype. Here we comprehensively map variation in HNF1B with respect to epithelial ovarian cancer risk and analyse DNA methylation and expression profiles across histological subtypes. Different single-nucleotide polymorphisms associate with invasive serous (rs7405776 odds ratio (OR)=1.13, P=3.1 × 10(-10)) and clear cell (rs11651755 OR=0.77, P=1.6 × 10(-8)) epithelial ovarian cancer. Risk alleles for the serous subtype associate with higher HNF1B-promoter methylation in these tumours. Unmethylated, expressed HNF1B, primarily present in clear cell tumours, coincides with a CpG island methylator phenotype affecting numerous other promoters throughout the genome. Different variants in HNF1B associate with risk of serous and clear cell epithelial ovarian cancer; DNA methylation and expression patterns are also notably distinct between these subtypes. These findings underscore distinct mechanisms driving different epithelial ovarian cancer histological subtypes.

Background: Endometriosis is a risk factor for epithelial ovarian cancer; however, whether this risk extends to all invasive histological subtypes or borderline tumours is not clear. We undertook an international collaborative study to assess the association between endometriosis and histological subtypes of ovarian cancer., Methods: Data from 13 ovarian cancer case-control studies, which were part of the Ovarian Cancer Association Consortium, were pooled and logistic regression analyses were undertaken to assess the association between self-reported endometriosis and risk of ovarian cancer. Analyses of invasive cases were done with respect to histological subtypes, grade, and stage, and analyses of borderline tumours by histological subtype. Age, ethnic origin, study site, parity, and duration of oral contraceptive use were included in all analytical models., Findings: 13 226 controls and 7911 women with invasive ovarian cancer were included in this analysis. 818 and 738, respectively, reported a history of endometriosis. 1907 women with borderline ovarian cancer were also included in the analysis, and 168 of these reported a history of endometriosis. Self-reported endometriosis was associated with a significantly increased risk of clear-cell (136 [20·2%] of 674 cases vs 818 [6·2%] of 13 226 controls, odds ratio 3·05, 95% CI 2·43-3·84, p<0·0001), low-grade serous (31 [9·2%] of 336 cases, 2·11, 1·39-3·20, p<0·0001), and endometrioid invasive ovarian cancers (169 [13·9%] of 1220 cases, 2·04, 1·67-2·48, p<0·0001). No association was noted between endometriosis and risk of mucinous (31 [6·0%] of 516 cases, 1·02, 0·69-1·50, p=0·93) or high-grade serous invasive ovarian cancer (261 [7·1%] of 3659 cases, 1·13, 0·97-1·32, p=0·13), or borderline tumours of either subtype (serous 103 [9·0%] of 1140 cases, 1·20, 0·95-1·52, p=0·12, and mucinous 65 [8·5%] of 767 cases, 1·12, 0·84-1·48, p=0·45)., Interpretation: Clinicians should be aware of the increased risk of specific subtypes of ovarian cancer in women with endometriosis. Future efforts should focus on understanding the mechanisms that might lead to malignant transformation of endometriosis so as to help identify subsets of women at increased risk of ovarian cancer., Funding: Ovarian Cancer Research Fund, National Institutes of Health, California Cancer Research Program, California Department of Health Services, Lon V Smith Foundation, European Community's Seventh Framework Programme, German Federal Ministry of Education and Research of Germany, Programme of Clinical Biomedical Research, German Cancer Research Centre, Eve Appeal, Oak Foundation, UK National Institute of Health Research, National Health and Medical Research Council of Australia, US Army Medical Research and Materiel Command, Cancer Council Tasmania, Cancer Foundation of Western Australia, Mermaid 1, Danish Cancer Society, and Roswell Park Alliance Foundation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The aim of the study was to determine whether polymorphism in the GCM1 gene is associated with pregnancy induced hypertension (PIH) in a case-control study of mother-baby dyads. Predominantly Hispanic women, ages 15-45, with (n=136) and without (n=169) PIH were recruited. We genotyped four polymorphisms in the GCM1 gene and examined the association with PIH using both logistic regression and likelihood expectation maximization (LEM) to adjust for intra-familial correlation between genotypes. Maternal genotype was not associated with PIH for any polymorphisms examined. Fetal genotype, however, was associated with maternal risk of PIH. Mothers carrying a fetus with ≥1 copy of the minor (C) allele for rs9349655 were less likely to develop PIH than women carrying a fetus with the GG genotype (parity-adjusted OR=0.44, 95% Cl: 0.21, 0.94). The trend of decreasing risk with increasing C alleles was also statistically significant (OR(trend)=0.41 95% Cl: 0.20, 0.85). The minor alleles for the other three SNPs also appear to be associated with protection. Multilocus analyses of fetal genotypes showed that the protective effect of carrying minor alleles at rs9349655 and rs13200319 (non-significant) remained unchanged when adjusting for genotypes at the other loci. However, the apparent (non-significant) effect of rs2816345 and rs2518573 disappeared when adjusting for rs9349655. In conclusion, we found that a fetal GCM1 polymorphism is significantly associated with PIH in a predominantly Hispanic population. These results suggest that GCM1 may represent a fetal-effect gene, where risk to the mother is conferred only through carriage by the fetus.

Introduction: Bilateral mucinous cystadenoma of the ovary are extremely rare. These tumors are benign and might lead to abdominal distension, if no secondary symptoms occur and patient delay the consultation of physicians., Case: A 60-year-old patient was admitted to the internal medicine department for constipation and dyspnoea. Transabdominal punctions were performed because of suspected ascites. Finally the patient was transferred to the gynecological department after forced diuresis did not reduce the suspected ascites and a CT scan showed large intraabdominal masses. Tumor excision was initiated and final histology revealed bilateral mucinous cystadenoma of the ovaries., Discussion: Huge intraabdominal tumors that almost double a patient's body weight can hardly be malign. Total tumor excision is necessary because the heterogeneous composition requires careful examination by pathologists to rule out borderline tumors and non-invasive carcinomas. After tumor excision an abdominal wall reconstruction might be necessary because of the laxity and redundancy of the skin.