When and how should peritoneal endometriosis be operated on in order to improve fertility rates and symptoms? The experience and outcomes of nearly 100 cases

Purpose: To analyze the follow-up results of patients suffering from symptomatic early-stage endometriosis after a consistent laparoscopic peritoneal stripping of the altered peritoneum (peritoneal endometriosis and surrounding inflamed tissue) was performed. This type of endometriosis is resistant to medical therapy and/or impairs fertility. Methods: Using our prospectively maintained database, we were able to identify all symptomatic women with the suspicion of only peritoneal endometriosis who underwent laparoscopy at our endometriosis center over a period of 5 years. All procedures were carried out in a standardized fashion by one single surgeon, who is highly experienced in minimal invasive surgery, and included a suspended hormonal pretreatment for 2 months. Postoperative outcomes including complications, fertility and recurrence rates were analysed. Results: Laparoscopic peritonectomy was performed on 94 women. Follow-up data were available in 87% of these cases. At the time of surgery, almost all patients tested showed signs of stage I or II endometriosis (44.7 and 48.9%, respectively). More than three-quarters of the women reported pain relief, inter alia, due to the post-surgical hormonal therapy. About one-third of the patients wanted to have children after the procedure. 62% of them became pregnant and the majority did so without the need for assisted reproductive therapy. In seven women a re-operation was performed. Conclusion: According to our data, a consistent excision of altered peritoneum followed by adjuvant hormonal therapy and multimodal concepts results in better outcomes for the patient, particularly in regards to pregnancy and recurrence rates

Optimized culture conditions for tissue explants of uterine leiomyoma

Background: Uterine leiomyomas are the most common benign tumours in women, which arise from smooth muscle cells of the uterine myometrium and usually are multicentric. In spite of their frequency pathogenesis is widely unknown, mainly due to the absence of a suitable model system. We describe the systematic optimization of culturing leiomyoma tissue explants in an economical and effective ex vivo system. Methods: Different concentrations of oxygen, different media, sera, hormones, and growth factor supplements were tested. Immunohistochemical stainings with antibodies against hormone receptors as well as specifying proliferation and apoptotic indices and real-time PCR were performed. Results: Main parameters for culturing myoma tissue explants were tested for finding an optimal protocol. Standard medium D-MEM-F12 in combination with the use of horse serum in a reduced concentration of 1% turned out to be optimal for these tissue cultures as well as the addition of estradiol and epidermal growth factor EGF to media. Reduced oxygen content in the incubator air showed no positive effect. Conclusions: For culturing tissue explants of uterine leiomyoma several conditions were optimized. The established tissue culture model allows examining the effects of known and potential therapeutic substances and the influence of immune competent cells in the process of tumour formation to find new targets for medical treatmen

Multicenter evaluation of blood-based biomarkers for the detection of endometriosis and adenomyosis: A prospective non-interventional study.

OBJECTIVE To evaluate blood-based biomarkers to detect endometriosis and/or adenomyosis across nine European centers (June 2014-April 2018). METHODS This prospective, non-interventional study assessed the diagnostic accuracy of 54 blood-based biomarker immunoassays in samples from 919 women (aged 18-45 years) with suspicion of endometriosis and/or adenomyosis versus symptomatic controls. Endometriosis was stratified by revised American Society for Reproductive Medicine stage. Symptomatic controls were "pathologic symptomatic controls" or "pathology-free symptomatic controls". The main outcome measure was receiver operating characteristic-area under the curve (ROC-AUC) and Wilcoxon P values corrected for multiple testing (q values). RESULTS CA-125 performed best in "all endometriosis cases" versus "all symptomatic controls" (AUC 0.645, 95% confidence interval [CI] 0.600-0.690, q < 0.001) and increased (P < 0.001) with disease stage. In "all endometriosis cases" versus "pathology-free symptomatic controls", S100-A12 performed best (AUC 0.692, 95% CI 0.614-0.769, q = 0.001) followed by CA-125 (AUC 0.649, 95% CI 0.569-0.729, q = 0.021). In "adenomyosis only cases" versus "symptomatic controls" or "pathology-free symptomatic controls", respectively, the top-performing biomarkers were sFRP-4 (AUC 0.615, 95% CI 0.551-0.678, q = 0.045) and S100-A12 (AUC 0.701, 95% CI 0.611-0.792, q = 0.004). CONCLUSION This study concluded that no biomarkers tested could diagnose or rule out endometriosis/adenomyosis with high certainty

Entrainment and motor emulation approaches to joint action: alternatives or complementary approaches?

Joint actions, such as music and dance, rely crucially on the ability of two, or more, agents to align their actions with great temporal precision. Within the literature that seeks to explain how this action alignment is possible, two broad approaches have appeared. The first, what we term the entrainment approach, has sought to explain these alignment phenomena in terms of the behavioral dynamics of the system of two agents. The second, what we term the emulator approach, has sought to explain these alignment phenomena in terms of mechanisms, such as forward and inverse models, that are implemented in the brain. They have often been pitched as alternative explanations of the same phenomena; however, we argue that this view is mistaken, because, as we show, these two approaches are engaged in distinct, and not mutually exclusive, explanatory tasks. While the entrainment approach seeks to uncover the general laws that govern behavior the emulator approach seeks to uncover mechanisms. We argue that is possible to do both and that the entrainment approach must pay greater attention to the mechanisms that support the behavioral dynamics of interest. In short, the entrainment approach must be transformed into a neuroentrainment approach by adopting a mechanistic view of explanation and by seeking mechanisms that are implemented in the brain

Artificial Gravity Reveals that Economy of Action Determines the Stability of Sensorimotor Coordination

Background: When we move along in time with a piece of music, we synchronise the downward phase of our gesture with the beat. While it is easy to demonstrate this tendency, there is considerable debate as to its neural origins. It may have a structural basis, whereby the gravitational field acts as an orientation reference that biases the formulation of motor commands. Alternatively, it may be functional, and related to the economy with which motion assisted by gravity can be generated by the motor system

Sprouted Innervation into Uterine Transplants Contributes to the Development of Hyperalgesia in a Rat Model of Endometriosis

Endometriosis is an enigmatic painful disorder whose pain symptoms remain difficult to alleviate in large part because the disorder is defined by extrauteral endometrial growths whose contribution to pain is poorly understood. A rat model (ENDO) involves autotransplanting on abdominal arteries uterine segments that grow into vascularized cysts that become innervated with sensory and sympathetic fibers. ENDO rats exhibit vaginal hyperalgesia. We used behavioral, physiological, and immunohistochemical methods to test the hypothesis that cyst innervation contributes to the development of this hyperalgesia after transplant. Rudimentary sensory and sympathetic innervation appeared in the cysts at two weeks, sprouted further and more densely into the cyst wall by four weeks, and matured by six weeks post-transplant. Sensory fibers became abnormally functionally active between two and three weeks post-transplant, remaining active thereafter. Vaginal hyperalgesia became significant between four and five weeks post-transplant, and stabilized after six to eight weeks. Removing cysts before they acquired functional innervation prevented vaginal hyperalgesia from developing, whereas sham cyst removal did not. Thus, abnormally-active innervation of ectopic growths occurs before hyperalgesia develops, supporting the hypothesis. These findings suggest that painful endometriosis can be classified as a mixed inflammatory/neuropathic pain condition, which opens new avenues for pain relief. The findings also have implications beyond endometriosis by suggesting that functionality of any transplanted tissue can be influenced by the innervation it acquires

Testing Multiple Coordination Constraints with a Novel Bimanual Visuomotor Task

The acquisition of a new bimanual skill depends on several motor coordination constraints. To date, coordination constraints have often been tested relatively independently of one another, particularly with respect to isofrequency and multifrequency rhythms. Here, we used a new paradigm to test the interaction of multiple coordination constraints. Coordination constraints that were tested included temporal complexity, directionality, muscle grouping, and hand dominance. Twenty-two healthy young adults performed a bimanual dial rotation task that required left and right hand coordination to track a moving target on a computer monitor. Two groups were compared, either with or without four days of practice with augmented visual feedback. Four directional patterns were tested such that both hands moved either rightward (clockwise), leftward (counterclockwise), inward or outward relative to each other. Seven frequency ratios (3∶1, 2∶1, 3∶2, 1∶1, 2∶3. 1∶2, 1∶3) between the left and right hand were introduced. As expected, isofrequency patterns (1∶1) were performed more successfully than multifrequency patterns (non 1∶1). In addition, performance was more accurate when participants were required to move faster with the dominant right hand (1∶3, 1∶2 and 2∶3) than with the non-dominant left hand (3∶1, 2∶1, 3∶2). Interestingly, performance deteriorated as the relative angular velocity between the two hands increased, regardless of whether the required frequency ratio was an integer or non-integer. This contrasted with previous finger tapping research where the integer ratios generally led to less error than the non-integer ratios. We suggest that this is due to the different movement topologies that are required of each paradigm. Overall, we found that this visuomotor task was useful for testing the interaction of multiple coordination constraints as well as the release from these constraints with practice in the presence of augmented visual feedback