Search

There is an increasing understanding that some mitral valve pathologies have developmental origins. The time course of valvulogenesis varies by animal model; in cattle, the branched chordae tendineae architecture becomes fully developed at full term. The mechanism by which chordae tendineae bifurcate during fetal development remains unknown. The current study presents a detailed description of bovine chordae tendineae formation and bifurcation during fetal development. Analysis of Movat Pentachrome-stained histological sections of the developing mitral valve apparatus was accompanied by micro-CT imaging. TEM imaging of chordae branches and common trunks allowed the measurement of collagen fibril diameter distributions. We observed a proteoglycan-rich “transition zone” at the junction between the fetal mitral valve anterior leaflet and chordae tendineae with “perforations” lined by MMP1/2 and Ki-67 expressing endothelial cells. This region also contained clusters of proliferating endothelial cells within the bulk of the tissue. We hypothesize this zone marks a region where chordae tendineae bifurcate during fetal development. In particular, perforations created by localized MMP activity serve as a site for the initiation of a “split” of a single chordae attachment into two. This is supported by TEM results that suggest a similar population of collagen fibrils runs from the branches into a common trunk. A clear understanding of normal mitral valvulogenesis and its signaling mechanisms will be crucial in developing therapeutics and/or tissue-engineered valve replacements.

Approximately 78% of women between the ages of 45 and 64 years have prophylactic oophorectomy when hysterectomy is performed for benign disease to prevent the development of ovarian cancer. However, after menopause, the ovary continues to produce androstenedione and testosterone in significant amounts and these androgens are converted in fat, muscle, and skin into estrone. Evidence suggests that oophorectomy increases the subsequent risk of coronary heart disease (CHD) and osteoporosis and whereas 14,000 women die of ovarian cancer every year nearly 490,000 women die of heart disease and 48,000 women die within 1 year after hip fracture. PubMed and the Cochrane database were used to identify studies that examined the incidence of disease and mortality from 5 conditions that seem to be related to ovarian hormones: CHD, ovarian cancer, breast cancer, stroke and hip fracture, and also data for death from all other causes. The data were applied to a Markov decision analytic computer model to calculate risk estimates for mortality from these conditions until the age of 80. The model shows for a hypothetical cohort of 10,000 women undergoing hysterectomy and who chose oophorectomy (vs. ovarian conservation) between the ages of 50 and 54 [without estrogen therapy(ET)], that by the time they reach age 80, 47 fewer women will have died from ovarian cancer, but 838 more women will have died from CHD and 158 more will have died from hip fracture. Therefore, the decision to perform prophylactic oophorectomy should be approached with great caution for the majority of women who are at low risk of developing ovarian cancer. [ABSTRACT FROM AUTHOR]

If there's no cancer present, why remove a woman's ovaries during hysterectomy? Does the reduced risk of ovarian cancer outweigh the consequences of eliminating the protective hormones secreted by a healthy pair of ovaries? A team of researchers offers some thought-provoking conclusions. [ABSTRACT FROM AUTHOR]

Abstract Background Due to a paucity of data regarding the availability and efficacy of equipment, health promotion methods and materials currently used by health professionals for the management of patients with non-communicable diseases (NCDs) at primary health care (PHC) facilities in Cape Town, an audit was undertaken. Methods A multi-centre cross-sectional study was undertaken to interview patients (n = 580) with NCDs at 30 PHC facilities. A questionnaire was used to obtain information on preferences for health promotion methods for lifestyle modification. Individual semi-structured interviews were conducted with selected health professionals (n = 14) and captured using a digital recorder. Data were transferred to the Atlas ti software programme and analysed using a thematic content analysis approach. Results Blood pressure measurement (97.6%) was the most common diagnostic test used, followed by weight measurement (88.3%), urine (85.7%) and blood glucose testing (80.9%). Individual lifestyle modification counselling was the preferred health education method of choice for the majority of patients. Of the 64% of patients that selected chronic clubs/support groups as a method of choice, only a third rated this as their first choice. Pamphlets, posters and workshops/group counselling sessions were the least preferred methods with only 9%, 13% and 11% of patients choosing these as their first choice, respectively. In an individual counselling setting 44.7% of patients reported that they would prefer to be counselled by a doctor, followed by a nurse (16.9%), health educator (8.8%) and nutrition advisor (4.8%). Health professionals identified numerous barriers to education and counselling. These can be summarised as a lack of resources, including time, space and equipment; staff-related barriers such as staff shortage and staff turnover; and patient-related barriers such as patient load and patient non-compliance. Conclusion The majority of patients attending PHC facilities want to receive lifestyle modification education. There is not however, one specific method that can be regarded as the gold standard. Patients’ preferences regarding health education methods differ, and they are more likely to be susceptible to methods that do not involve much reading. Health education materials such as posters, pamphlets and booklets should be used to supplement information received during counselling or support group sessions.

Clinical decision-making regarding syncope poses challenges, with risk of physician error due to the elusive nature of syncope pathophysiology, diverse presentations, heterogeneity of risk factors, and limited therapeutic options. Artificial intelligence (AI)-based techniques, including machine learning (ML), deep learning (DL), and natural language processing (NLP), can uncover hidden and nonlinear connections among syncope risk factors, disease features, and clinical outcomes. ML, DL, and NLP models can analyze vast amounts of data effectively and assist physicians to help distinguish true syncope from other types of transient loss of consciousness. Additionally, short-term adverse events and length of hospital stay can be predicted by these models. In syncope research, AI-based models shift the focus from causality to correlation analysis between entities. This prompts the search for patterns rather than defining a hypothesis to be tested a priori. Furthermore, education of students, doctors, and health care providers engaged in continuing medical education may benefit from clinical cases of syncope interacting with NLP-based virtual patient simulators. Education may be of benefit to patients. This article explores potential strengths, weaknesses, and proposed solutions associated with utilization of ML and DL in syncope diagnosis and management. Three main topics regarding syncope are addressed: 1) clinical decision-making; 2) clinical research; and 3) education. Within each domain, we question whether "AI will be better than humans," seeking evidence to support our objective inquiry., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: Postural tachycardia syndrome (PTS) is a novel identified sequela of COVID-19 infection. This observational study describes clinical presentation, testing, and treatment response in seven patients diagnosed with PTS following COVID-19 infection., Case Summary: A total of seven active patients (three collegiate athletes, one recreational athlete, two registered nurses, one hospitality employee), age 24 ± 6 years, and six females were followed for a mean of 152 ± 105 days after contracting COVID-19. Tilt table was performed to establish the diagnosis. The most common presenting symptoms were palpitations (7/7), dyspnoea (6/7), and gastrointestinal complaints (5/7). One patient required hospitalization for symptom management. The mean latency of PTS onset following COVID-19 was 21 ± 15 days. Electrocardiograms (ECGs) demonstrated sinus rhythm in all patients, one with resting sinus tachycardia. Echocardiogram demonstrated normal systolic and diastolic left ventricular function in all patients. On tilt table testing, baseline heart rate (HR) was 72 ± 12 with maximum HR reaching 136 ± 13. Six of seven patients failed to respond to supportive therapy alone, and two patients failed medical management with ivabradine, midodrine, and/or metoprolol. Of three severely symptomatic patients, two demonstrated some degree of clinical recovery with intravenous immunoglobulin (IVIG)., Discussion: This novel case series describes the development of PTS in the context of COVID-19 infection. Severity of symptoms and response to treatment was heterogeneous. Interestingly, patients were poorly responsive to traditional PTS treatments, but IVIG showed potential as a possible therapeutic strategy for refractory PTS in two patients, particularly following COVID-19 infection., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Study Objective: To evaluate the baseline and postoperative changes in quality of life and symptom-severity scores in women undergoing laparoscopic or open abdominal myomectomy for symptomatic myomas., Design: Prospective cohort study of patients choosing myomectomy for symptomatic uterine myomas., Setting: Academic medical center., Patients: A total of 143 women enrolled in the study. Of these, 80 women completed both a preoperative questionnaire and at least 1 postoperative questionnaire between 6 and 27 months after surgery., Interventions: A total of 52 women had open abdominal myomectomy, and 28 had laparoscopic myomectomy between October 2014 and September 2017., Measurements and Main Results: The results of the Uterine Fibroid Symptom and Health-Related Quality-of-Life Questionnaire were compared before and after laparoscopic or open myomectomy. Women undergoing open abdominal myomectomy had larger and more numerous myomas than women undergoing laparoscopic myomectomy. Baseline quality-of-life scores were less adversely affected for women having laparoscopic myomectomy (mean [standard deviation], 57 [24] laparoscopic vs 43 [19] open abdominal, p = .01). However, baseline symptom-severity scores were statistically similar (49 [22] for laparoscopic and 57 [20] for open abdominal, p = .08) approaches. Six to 12 months after surgery, both open abdominal and laparoscopic surgeries provided excellent and similar improvements in symptom-severity and quality of life (postoperative symptoms severity scores, mean [standard deviation], 20 [14] laparoscopic vs 13 [11] open abdominal, p = .24 and quality-of-life scores, mean [standard deviation], 91 [16] laparoscopic vs 88 [17] open abdominal, p = .49). These improvements were sustained for women who returned questionnaires up to 27 months of follow-up., Conclusion: Women with symptomatic myomas have a compromised quality of life, and they experience a similarly dramatic improvement in quality of life and decrease in symptom-severity after both laparoscopic and open abdominal myomectomies., (Copyright © 2020 AAGL. Published by Elsevier Inc. All rights reserved.)

Objective: To describe and illustrate a massive cotyledenoid leiomyoma treated with uterine-conserving surgery., Design: Case report., Setting: Medical center., Patients: A 39-year-old woman with a large abdominal mass and a magnetic resonance imaging scan showing a 28-cm multi-lobulated mass., Interventions: Laparotomy and myomectomy., Main Outcome Measures: Recurrence and need for repeat surgery., Results: No recurrence at 8 years of follow-up., Conclusions: Cotyledonoid leiomyomas are rare. These benign tumors may be suspected preoperatively based on MRI appearance. Frozen section suggests a benign process and uterine-conserving surgery may be successfully accomplished., (© 2020 The Author(s).)

Purpose of Review: Minimally invasive gynecologic procedures, in particular laparoscopic hysterectomy and myomectomy, often require tissue morcellation., Recent Findings: Whether morcellated or not, myometrial cells can be found in the abdomen and pelvis after either laparoscopic or open myomectomy. Following morcellation, careful inspection for and removal of tissue fragments and copious irrigation and suctioning of fluid can remove residual tissue and cells without the use of containment bags. The dogma of not 'cutting-through' cancer is not correct for many surgical specialties and irrelevant with regards to leiomyosarcoma (LMS) and minimally invasive gynecologic surgery. Eliminating residual disease in the pelvis and abdomen should be the goal of myomectomy or hysterectomy., Summary: Morcellation of excised tissue is necessary for many women with symptomatic fibroids who choose to undergo laparoscopic myomectomy or hysterectomy. LMS is an uncommon disease, with a poor prognosis due to early hematogenous metastasis to lung, bone and liver. Preoperatively, it is often difficult to differentiate from benign fibroids. LMS has a high propensity for local recurrence despite performance of total hysterectomy. Efforts to remove all tissue and cells from the pelvis and abdomen should be the goal of minimally invasive surgery with morcellation.

Vitamin C, or ascorbic acid, both tightens the endothelial permeability barrier in basal cells and also prevents barrier leak induced by inflammatory agents. Barrier tightening by ascorbate in basal endothelial cells requires nitric oxide derived from activation of nitric oxide synthase. Although ascorbate did not affect cyclic AMP levels in our previous study, there remains a question of whether it might activate downstream cyclic AMP-dependent pathways. In this work, we found in both primary and immortalized cultured endothelial cells that ascorbate tightened the endothelial permeability barrier by ∼30%. In human umbilical vein endothelial cells, this occurred at what are likely physiologic intracellular ascorbate concentrations. In so doing, ascorbate decreased measures of oxidative stress and also flattened the cells to increase cell-to-cell contact. Inhibition of downstream cyclic AMP-dependent proteins via protein kinase A did not prevent ascorbate from tightening the endothelial permeability barrier, whereas inhibition of Epac1 did block the ascorbate effect. Although Epac1 was required, its mediator Rap1 was not activated. Furthermore, ascorbate acutely stabilized microtubules during depolymerization induced by colchicine and nocodazole. Over several days in culture, ascorbate also increased the amount of stable acetylated α-tubulin. Microtubule stabilization was further suggested by the finding that ascorbate increased the amount of Epac1 bound to α-tubulin. These results suggest that physiologic ascorbate concentrations tighten the endothelial permeability barrier in unstimulated cells by stabilizing microtubules in a manner downstream of cyclic AMP that might be due both to increasing nitric oxide availability and to scavenging of reactive oxygen or nitrogen species., (Copyright © 2016 the American Physiological Society.)

In November 2014, the Food and Drug Administration (FDA) calculated that for every 498 women having surgery for presumed fibroids, one woman would be found to have an occult leiomyosarcoma (LMS). The FDA issued a safety communication warning against the use of laparoscopic morcellators in the majority of women undergoing myomectomy or hysterectomy for treatment of fibroids. This communication was prompted by concern that if a patient had an occult LMS, the morcellator might spread tumor cells within the peritoneal cavity. We submit that the FDA directive was based on a flawed and misleading analysis. More rigorous evidence estimates the prevalence of LMS among women operated upon for presumed uterine fibroids at approximately one in 2000 women, significantly lower than the FDA's estimate. In addition, there is no reliable evidence that morcellation influences survival or that power-morcellation is inferior to vaginal or mini-lap morcellation with a scalpel. Recent publication shows that open surgery carries more risk for women when compared with minimally invasive surgery. Although the possibility of occult LMS should be considered by women and their gynecologists, we suggest that current morcellation techniques be continued for women who wish to benefit from minimally invasive surgery. Investigation into new and, hopefully, better morcellating devices may make the procedure safer for women.

The U.S. Food and Drug Administration (FDA) is warning against the use of laparoscopic power morcellators in the majority of women undergoing myomectomy or hysterectomy for the treatment of leiomyomas because of the concern for inadvertent spread of tumor cells if an undiagnosed cancer were present. The authors, representing a 45-member review group, reviewed the current literature to formulate prevalence rates of leiomyosarcoma in women with presumed leiomyomas and to asses reliable data regarding patient survival after morcellation. The authors disagree with the FDA's methodology in reaching their conclusion and provide clinical recommendations for care of women with leiomyomas who are planning surgery.

Vascular endothelial growth factor (VEGF) increases endothelial barrier permeability, an effect that may contribute to macular edema in diabetic retinopathy. Since vitamin C, or ascorbic acid, can tighten the endothelial permeability barrier, we examined whether it could prevent the increase in permeability due to VEGF in human umbilical vein endothelial cells (HUVECs). As previously observed, VEGF increased HUVEC permeability to radiolabeled inulin within 60 min in a concentration-dependent manner. Loading the cells with increasing concentrations of ascorbate progressively prevented the leakage caused by 100 ng/ml VEGF, with a significant inhibition at 13 µM and complete inhibition at 50 µM. Loading cells with 100 µM ascorbate also decreased the basal generation of reactive oxygen species and prevented the increase caused by both 100 ng/ml VEGF. VEGF treatment decreased intracellular ascorbate by 25%, thus linking ascorbate oxidation to its prevention of VEGF-induced barrier leakage. The latter was blocked by treating the cells with 60 µM L-NAME (but not D-NAME) as well as by 30 µM sepiapterin, a precursor of tetrahydrobiopterin that is required for proper function of endothelial nitric oxide synthase (eNOS). These findings suggest that VEGF-induced barrier leakage uncouples eNOS. Ascorbate inhibition of the VEGF effect could thus be due either to scavenging superoxide or to peroxynitrite generated by the uncoupled eNOS, or more likely to its ability to recycle tetrahydrobiopterin, thus avoiding enzyme uncoupling in the first place. Ascorbate prevention of VEGF-induced increases in endothelial permeability opens the possibility that its repletion could benefit diabetic macular edema.

Surgical blood loss of >1000 mL or blood loss that requires a blood transfusion usually defines intraoperative hemorrhage. Intraoperative hemorrhage has been reported in 1% to 2% of hysterectomy studies. Cardiovascular instability with significant hypotension often results from a loss of 30% to 40% of the patient's blood volume and >40% blood loss is life threatening. Preparation, planning, and practicing for a massive hemorrhage is essential for all surgeons and gynecologic operating room teams. Emergency steps should be written and posted in the operating room and rehearsed quarterly.

Intracellular ascorbate (vitamin C) has previously been shown to tighten the endothelial barrier and maintain barrier integrity during acute inflammation in vitro. However, the downstream effectors of ascorbate in the regulation of endothelial permeability remain unclear. In this study, we evaluated ascorbate as a mediator of thrombin-induced barrier permeabilization in human umbilical vein endothelial cells and their immortalized hybridoma line, EA.hy926. We found that the vitamin fully prevented increased permeability to the polysaccharide inulin by thrombin in a dose-dependent manner, and it took effect both before and after subjection to thrombin. Thrombin exposure consumed intracellular ascorbate but not the endogenous antioxidant GSH. Likewise, the antioxidants dithiothreitol and tempol did not reverse permeabilization. We identified a novel role for ascorbate in preserving cAMP during thrombin stimulation, resulting in two downstream effects. First, ascorbate maintained the cortical actin cytoskeleton in a Rap1- and Rac1-dependent manner, thus preserving stable adherens junctions between adjacent cells. Second, ascorbate prevented actin polymerization and formation of stress fibers by reducing the activation of RhoA and phosphorylation of myosin light chain. Although ascorbate and thrombin both required calcium for their respective effects, ascorbate did not prevent thrombin permeabilization by obstructing calcium influx. However, preservation of cAMP by ascorbate was found to depend on both the production of nitric oxide by endothelial nitric-oxide synthase, which ascorbate is known to activate, and the subsequent generation cGMP by guanylate cyclase. Together, these data implicate ascorbate in the prevention of inflammatory endothelial barrier permeabilization and explain the underlying signaling mechanism., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)

Intracellular vitamin C, or ascorbic acid, has been shown to prevent the apoptosis of cultured vascular pericytes under simulated diabetic conditions. We sought to determine the mechanism by which ascorbate is transported into pericytes prior to exerting this protective effect. Measuring intracellular ascorbate, we found that pericytes display a linear uptake over 30 min and an apparent transport Km of 21 μM, both of which are consistent with activity of the Sodium-dependent Vitamin C Transporter 2 (SVCT2). Uptake of both radiolabeled and unlabeled ascorbate was prevented by inhibiting SVCT2 activity, but not by inhibiting the activity of GLUT-type glucose transporters, which import dehydroascorbate to also generate intracellular ascorbate. Likewise, uptake of dehydroascorbate was prevented with the inhibition of GLUTs, but not by inhibiting the SVCT2, indicating substrate specificity of both transporters. Finally, presence of the SVCT2 in pericytes was confirmed by western blot analysis, and immunocytochemistry was used to localize it to the plasma membrane and intracellular sites. Together, these data clarify previous inconsistencies in the literature, implicate SVCT2 as the pericyte ascorbate transporter, and show that pericytes are capable of concentrating intracellular ascorbate against a gradient in an energy- and sodium-dependent fashion., (Copyright © 2015 Elsevier Inc. All rights reserved.)

There is concern that morcellation of occult leiomyosarcomas during surgery to treat presumed myomas may substantially worsen patient outcome. We reviewed the existing medical literature to better understand whether such a risk was demonstrable and, if so, what the magnitude of that risk might be. We identified 4864 articles initially, of which 60 were evaluated in full. Seventeen were found to have outcomes information and are included in this review. Six studies addressed the question of whether morcellation of occult leiomyosarcomas resulted in inferior outcomes as compared with en bloc uterine and tumor removal. In these 6 studies, results suggested that en bloc removal may result in improved survival and less recurrence; however, the data are highly biased and of poor quality. There is no reliable evidence that morcellation, power or otherwise, substantially results in tumor upstaging. There is no evidence from these 17 studies that power morcellation differs in any way from other types of morcellation or even simple myomectomy insofar as patient outcome. Whether electromechanical morcellation poses a unique danger to the patient with occult leiomyosarcoma is an unanswered question and one clearly in need of more extensive investigation before conclusions are drawn and policies created., (Copyright © 2015 AAGL. Published by Elsevier Inc. All rights reserved.)

High glucose concentrations due to diabetes increase apoptosis of vascular pericytes, impairing vascular regulation and weakening vessels, especially in brain and retina. We sought to determine whether vitamin C, or ascorbic acid, could prevent such high glucose-induced increases in pericyte apoptosis. Culture of human microvascular brain pericytes at 25 mM compared to 5mM glucose increased apoptosis measured as the appearance of cleaved caspase 3. Loading the cells with ascorbate during culture decreased apoptosis, both at 5 and 25 mM glucose. High glucose-induced apoptosis was due largely to activation of the receptor for advanced glycation end products (RAGE), since it was prevented by specific RAGE inhibition. Culture of pericytes for 24h with RAGE agonists also increased apoptosis, which was completely prevented by inclusion of 100 μM ascorbate. Ascorbate also prevented RAGE agonist-induced apoptosis measured as annexin V binding in human retinal pericytes, a cell type with relevance to diabetic retinopathy. RAGE agonists decreased intracellular ascorbate and GSH in brain pericytes. Despite this evidence of increased oxidative stress, ascorbate prevention of RAGE-induced apoptosis was not mimicked by several antioxidants. These results show that ascorbate prevents pericyte apoptosis due RAGE activation. Although RAGE activation decreases intracellular ascorbate and GSH, the prevention of apoptosis by ascorbate may involve effects beyond its function as an antioxidant., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Intraspecific assisted migration (ISAM) through seed transfer during artificial forest regeneration has been suggested as an adaptation strategy to enhance forest resilience and productivity under future climate. In this study, we assessed the risks and benefits of ISAM in white spruce based on long-term and multilocation, rangewide provenance test data. Our results indicate that the adaptive capacity and growth potential of white spruce varied considerably among 245 range-wide provenances sampled across North America; however, the results revealed that local populations could be outperformed by nonlocal ones. Provenances originating from south-central Ontario and southwestern Québec, Canada, close to the southern edge of the species' natural distribution, demonstrated superior growth in more northerly environments compared with local populations and performed much better than populations from western Canada and Alaska, United States. During the 19-28 years between planting and measurement, the southern provenances have not been more susceptible to freezing damage compared with local populations, indicating they have the potential to be used now for the reforestation of more northerly planting sites; based on changing temperature, these seed sources potentially could maintain or increase white spruce productivity at or above historical levels at northern sites. A universal response function (URF), which uses climatic variables to predict provenance performance across field trials, indicated a relatively weak relationship between provenance performance and the climate at provenance origin. Consequently, the URF from this study did not provide information useful to ISAM. The ecological and economic importance of conserving white spruce genetic resources in south-central Ontario and southwestern Québec for use in ISAM is discussed.

Observational studies suggest that elective bilateral oophorectomy may do more harm than good. Removing the ovaries at the time of hysterectomy for benign disease should be approached with caution, especially for women younger than age 50. For women who choose oophorectomy, some evidence suggests that menopausal estrogen therapy may ameliorate some of the increased risk. An informed consent process covering the risks and benefits of both oophorectomy and ovarian conservation is important.

A rare neurodevelopmental disorder in the Old Order Mennonite population called PMSE (polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome; also called Pretzel syndrome) is characterized by infantile-onset epilepsy, neurocognitive delay, craniofacial dysmorphism, and histopathological evidence of heterotopic neurons in subcortical white matter and subependymal regions. PMSE is caused by a homozygous deletion of exons 9 to 13 of the LYK5/STRADA gene, which encodes the pseudokinase STRADA, an upstream inhibitor of mammalian target of rapamycin complex 1 (mTORC1). We show that disrupted pathfinding in migrating mouse neural progenitor cells in vitro caused by STRADA depletion is prevented by mTORC1 inhibition with rapamycin or inhibition of its downstream effector p70 S6 kinase (p70S6K) with the drug PF-4708671 (p70S6Ki). We demonstrate that rapamycin can rescue aberrant cortical lamination and heterotopia associated with STRADA depletion in the mouse cerebral cortex. Constitutive mTORC1 signaling and a migration defect observed in fibroblasts from patients with PMSE were also prevented by mTORC1 inhibition. On the basis of these preclinical findings, we treated five PMSE patients with sirolimus (rapamycin) without complication and observed a reduction in seizure frequency and an improvement in receptive language. Our findings demonstrate a mechanistic link between STRADA loss and mTORC1 hyperactivity in PMSE, and suggest that mTORC1 inhibition may be a potential treatment for PMSE as well as other mTOR-associated neurodevelopmental disorders.

Objective: To report long-term mortality after oophorectomy or ovarian conservation at the time of hysterectomy in subgroups of women based on age at the time of surgery, use of estrogen therapy, presence of risk factors for coronary heart disease, and length of follow-up., Methods: This was a prospective cohort study of 30,117 Nurses' Health Study participants undergoing hysterectomy for benign disease. Multivariable adjusted hazard ratios for death from coronary heart disease, stroke, breast cancer, epithelial ovarian cancer, lung cancer, colorectal cancer, total cancer, and all causes were determined comparing bilateral oophorectomy (n=16,914) with ovarian conservation (n=13,203)., Results: Over 28 years of follow-up, 16.8% of women with hysterectomy and bilateral oophorectomy died from all causes compared with 13.3% of women who had ovarian conservation (hazard ratio 1.13, 95% confidence interval 1.06-1.21). Oophorectomy was associated with a lower risk of death from ovarian cancer (four women with oophorectomy compared with 44 women with ovarian conservation) and, before age 47.5 years, a lower risk of death from breast cancer. However, at no age was oophorectomy associated with a lower risk of other cause-specific or all-cause mortality. For women younger than 50 years at the time of hysterectomy, bilateral oophorectomy was associated with significantly increased mortality in women who had never used estrogen therapy but not in past and current users: assuming a 35-year lifespan after oophorectomy: number needed to harm for all-cause death=8, coronary heart disease death=33, and lung cancer death=50., Conclusions: Bilateral oophorectomy is associated with increased mortality in women aged younger than 50 years who never used estrogen therapy and at no age is oophorectomy associated with increased survival., Level of Evidence: I.

Leiomyomas are the most common pelvic tumors in women. These tumors are not always symptomatic but can cause abnormal uterine bleeding and anemia, pelvic pressure and pain, urinary frequency, and adverse reproductive outcomes-symptoms that can diminish the quality of life of women. Myomectomy is the primary treatment modality for women with symptomatic leiomyomas who are of reproductive age and desire future fertility. Myomectomy can significantly improve symptoms and quality of life and, in some clinical situations, improve reproductive outcomes. There are robust surgical outcome data supporting the use of a minimally invasive approach such as laparoscopy and hysteroscopy over laparotomy. Perioperative outcomes and return to normal activity are significantly better with a minimally invasive approach. Reproductive outcomes are not adversely affected. Detailed preoperative imaging is required for minimally invasive procedures to be successful. There are several evidence-based techniques that can be used to reduce blood loss during surgery. The role of robotic technology in enhancing surgical outcomes has not been clearly defined.

Determination of the reasonable treatment options and the appropriate clinical treatment of women with uterine fibroid tumors often depends on the ability of imaging modalities to accurately detect and localize fibroid tumors. Magnetic resonance imaging (MRI) gives the most complete evaluation (sizes, positions, number) of submucous, intramural, and subserosal myomas and is the most sensitive modality for the detection of small fibroid tumors. MRI allows the evaluation of fibroid tumor proximity to the bladder, rectum, and endometrial cavity, helps define what can be expected at surgery, and may help the gynecologist avoid missing fibroid tumors during surgery. MRI can also make the diagnosis of adenomyosis reliably and may be able to identify uterine sarcoma when present., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Case reports for uterine rupture subsequent to laparoscopic myomectomy were reviewed to determine whether common causal factors could be identified. Published cases were identified via electronic searches of PubMed, Google Scholar, and hand searches of references, and unpublished cases were obtained via E-mail queries to the AAGL membership and AAGL Listserve participants. Nineteen cases of uterine rupture after laparoscopic myomectomy were identified. The removed myomas ranged in size from 1 through 11 cm (mean, 4.5 cm). Only 3 cases involved multilayered closure of uterine defects. Electrosurgery was used for hemostasis in all but 2 cases. No plausible contributing factor could be found in one case [corrected]. It seems reasonable for surgeons to adhere to techniques developed for abdominal myomectomy including limited use of electrosurgery and multilayered closure of the myometrium. Nevertheless, individual wound healing characteristics may predispose to uterine rupture., (Copyright © 2010 AAGL. Published by Elsevier Inc. All rights reserved.)

Complications may occur during laparoscopic surgery, even with a skilled surgeon and under ideal circumstances; human error is inevitable. Videotaped procedures from malpractice cases are evaluated to ascertain potential contributing cognitive factors, systems errors, equipment issues, and surgeon training. Situation awareness and principles derived from aviation crew resource management may be adapted to help avoid systems error. The current process of surgical training may need to be reconsidered., (Copyright 2010 Elsevier Inc. All rights reserved.)

Surgical blood loss of more than 1000 mL or blood loss that requires a blood transfusion usually defines intraoperative hemorrhage. Intraoperative hemorrhage has been reported in 1% to 2% of hysterectomy studies. Preoperative evaluation of the patient can aid surgical planning to help prevent intraoperative hemorrhage or prepare for the management of hemorrhage, should it occur. To this effect, the medical and medication history and use of alternative medication must be gathered. This article discusses the methods of preoperative management of anemia, including use of iron, recombinant erythropoietin, and gonadotropin-releasing hormone agonists. The authors have also reviewed the methods of intraoperative and postoperative management of bleeding., (Copyright 2010 Elsevier Inc. All rights reserved.)

Bilateral oophorectomy at the time of hysterectomy for benign disease is commonly practiced to prevent the subsequent development of ovarian cancer. Currently, bilateral oophorectomy is performed in 55% of all U.S. women having a hysterectomy, with approximately 300,000 prophylactic oophorectomies performed every year. Observational studies show that estrogen deficiency, resulting from premenopausal or postmenopausal oophorectomy, is associated with higher risks of coronary artery disease, stroke, hip fracture, Parkinsonism, dementia, cognitive impairment, depression, and anxiety. These studies suggest that bilateral oophorectomy may do more harm than good. In women not at high risk for development of ovarian or breast cancer, removing the ovaries at the time of hysterectomy should be approached with caution., (Copyright 2010. Published by Elsevier Inc.)

Bilateral oophorectomy at the time of hysterectomy for benign disease is commonly practiced in order to prevent the subsequent development of ovarian cancer or other ovarian pathology that might require additional surgery. At present, bilateral oophorectomy is performed in 78% of women aged between 45 and 64 years having a hysterectomy, and a total of approximately 300,000 prophylactic oophorectomies are performed in the USA every year. Estrogen deficiency resulting from pre- and post-menopausal oophorectomies has been associated with higher risks of coronary heart disease, stroke, hip fracture, Parkinsonism, dementia, cognitive impairment, depression and anxiety in many studies. While ovarian cancer accounts for 14,800 deaths per year in the USA, coronary heart disease accounts for 350,000 deaths per year. In addition, 100,000 cases of dementia may be attributable annually to prior bilateral oophorectomy. At present, observational studies suggest that bilateral oophorectomy may do more harm than good. In women who are not at high risk of developing ovarian or breast cancer, removing the ovaries at the time of hysterectomy should be approached with caution.

Objective: To report long-term health outcomes and mortality after oophorectomy or ovarian conservation., Methods: We conducted a prospective, observational study of 29,380 women participants of the Nurses' Health Study who had a hysterectomy for benign disease; 16,345 (55.6%) had hysterectomy with bilateral oophorectomy, and 13,035 (44.4%) had hysterectomy with ovarian conservation. We evaluated incident events or death due to coronary heart disease (CHD), stroke, breast cancer, ovarian cancer, lung cancer, colorectal cancer, total cancers, hip fracture, pulmonary embolus, and death from all causes., Results: Over 24 years of follow-up, for women with hysterectomy and bilateral oophorectomy compared with ovarian conservation, the multivariable hazard ratios (HRs) were 1.12 (95% confidence interval [CI] 1.03-1.21) for total mortality, 1.17 (95% CI 1.02-1.35) for fatal plus nonfatal CHD, and 1.14 (95% CI 0.98-1.33) for stroke. Although the risks of breast (HR 0.75, 95% CI 0.68-0.84), ovarian (HR 0.04, 95% CI 0.01-0.09, number needed to treat=220), and total cancers (HR 0.90, 95% CI 0.84-0.96) decreased after oophorectomy, lung cancer incidence (HR=1.26, 95% CI 1.02-1.56, number needed to harm=190), and total cancer mortality (HR=1.17, 95% CI 1.04-1.32) increased. For those never having used estrogen therapy, bilateral oophorectomy before age 50 years was associated with an increased risk of all-cause mortality, CHD, and stroke. With an approximate 35-year life span after surgery, one additional death would be expected for every nine oophorectomies performed., Conclusion: Compared with ovarian conservation, bilateral oophorectomy at the time of hysterectomy for benign disease is associated with a decreased risk of breast and ovarian cancer but an increased risk of all-cause mortality, fatal and nonfatal coronary heart disease, and lung cancer. In no analysis or age group was oophorectomy associated with increased survival.

Objective: To investigate the effect of fibroids on fertility and of myomectomy in improving outcomes., Design: Systematic literature review and meta-analysis of existing controlled studies., Setting: Private center for Reproductive endocrinology and infertility., Patient(s): Women with fibroids and infertility., Intervention(s): A systematic literature review, raw data extraction and data analysis., Main Outcome Measure(s): Clinical pregnancy rate, spontaneous abortion rate, ongoing pregnancy/live birth rate, implantation rate, and preterm delivery rate in women with and without fibroids, and in women who underwent myomectomy., Result(s): Women with subserosal fibroids had no differences in their fertility outcomes compared with infertile controls with no myomas, and myomectomy did not change these outcomes compared with women with fibroids in situ. Women with intramural fibroids appear to have decreased fertility and increased pregnancy loss compared with women without such tumors, but study quality is poor. Myomectomy does not significantly increase the clinical pregnancy and live birth rates, but the data are scarce. Fibroids with a submucosal component led to decreased clinical pregnancy and implantation rates compared with infertile control subjects. Removal of submucous myomas appears likely to improve fertility., Conclusion(s): Fertility outcomes are decreased in women with submucosal fibroids, and removal seems to confer benefit. Subserosal fibroids do not affect fertility outcomes, and removal does not confer benefit. Intramural fibroids appear to decrease fertility, but the results of therapy are unclear. More high-quality studies need to be directed toward the value of myomectomy for intramural fibroids, focusing on issues such as size, number, and proximity to the endometrium.

We investigated adaptive variation in fall cold hardiness development based on the electrical conductivity of tissue diffusates (EC) among 20 aspen provenances from northwestern Ontario. Provenance accounted for over 40% of the total variation in cold injury for seven dates from September through November in three provenance trials. Principal component analysis was performed to summarize the combinations of results for all sampling sites, dates and temperatures (traits). Principal component (PC)-1 represented fully developed cold hardiness differences among provenances; PC-2 represented differences in the timing of the onset of cold hardiness development; and PC-3 represented a site-related difference in cold hardiness development. Heat sum in early summer and late summer precipitation together were the best predictors of absolute degree of cold hardiness (PC-1), whereas temperatures for mid- to late summer were best for predicting onset of cold hardiness development (PC-2). In a second study, we assessed the efficacy of chlorophyll fluorescence (CF) as a simpler technique for determining the cold hardiness of aspen stem samples. Fall cold hardiness of stem samples of 12 of the original 20 provenances was estimated by CF, and the results were evaluated by a visual scoring (VS) method. Correlations between EC and CF measurements from the two studies were moderately strong based on the extent of cold hardiness in October of each year, but were negative for September dates because of a later onset of cold hardiness in the EC study year. Although the EC and CF methods gave similar cold hardiness values for stem samples from 12 provenances, the CF method may be preferred to the EC or VS method for species with chlorophyllous stems because of its greater ease of use.

Purpose of Review: Oophorectomy is electively performed in approximately 300,000 US women per year who are having hysterectomy for benign disease., Recent Findings: New studies have suggested that elective oophorectomy may not be advisable for the majority of women, as it may lead to a higher risk of death from cardiovascular disease and hip fracture, and may result in a higher incidence of dementia and Parkinson's disease. Women with known BRCA 1/2 germ-line mutations clearly benefit from oophorectomy after childbearing., Summary: Prophylactic oophorectomy should be undertaken with caution in the majority of women with an average risk of ovarian cancer who are having a hysterectomy for benign disease.

Objective: To review the currently available literature regarding the current management alternatives available to women with uterine myomas., Design: Literature review of 198 articles pertaining to uterine myomas., Result(s): Many advances have been made in the management of uterine myomas. Watchful waiting; medical therapy; hysteroscopic myomectomy; endometrial ablation; laparoscopic myomectomy; abdominal myomectomy; abdominal, vaginal, and laparoscopic hysterectomy; uterine artery embolization; uterine artery occlusion; and focused ultrasound are now available., Conclusion(s): Many options are now available to women with uterine myomas. The presently available literature regarding the treatment of myomas is summarized.

Objective: To review the risks and benefits of elective oophorectomy and to make a clinical recommendation for an appropriate age when benefits of this procedure outweigh the risks., Design: The risks and benefits of oophorectomy as detailed in published articles are reviewed with regard to quality-of-life issues and mortality outcomes in oophorectomized versus non-oophorectomized women from five diseases linked to ovarian hormones (coronary heart disease, ovarian cancer, breast cancer, stroke, and hip fracture)., Results: Numerous reports link oophorectomy to higher rates of cardiovascular disease, osteoporosis, hip fractures, dementia, short-term memory impairment, decline in sexual function, decreased positive psychological well-being, adverse skin and body composition changes, and adverse ocular changes, as well as more severe hot flushes and urogenital atrophy. The potential benefits associated with oophorectomy include prevention of ovarian cancer, a decline in breast cancer risk, and a reduced risk of pelvic pain and subsequent ovarian surgery. In our study of long-term mortality after oophorectomy using Markov modeling, preservation of ovaries until women are at least aged 65 years was associated with higher survival rates. For women between ages 50 and 54 with hysterectomy and ovarian preservation, the probability of surviving to age 80 was 62% versus 54% if oophorectomy was performed. This 8% difference in survival is primarily due to fewer women dying from cardiovascular heart disease and/or hip fracture. This survival advantage far outweighs the 0.47% increased mortality rate from ovarian cancer prevented by oophorectomy. If surgery occurred between ages 55 and 59, the survival advantage was 4%. After age 64 there were no significant differences in survival rates. Prior literature supports our conclusion of a benefit over risk for ovarian conservation., Conclusions: Elective oophorectomy is associated with short-and long-term health consequences that merit serious consideration. For women with an average risk of ovarian cancer, ovarian conservation until at least age 65 seems to benefit long-term survival.