Frustrated peptide chains at the fibril tip control the kinetics of growth of amyloid-ß fibrils.

Amyloid fibrillization is an exceedingly complex process in which incoming peptide chains bind to the fibril while concertedly folding. The coupling between folding and binding is not fully understood. We explore the molecular pathways of association of Aß40 monomers to fibril tips by combining time-resolved in situ scanning probe microscopy with molecular modeling. The comparison between experimental and simulation results shows that a complex supported by nonnative contacts is present in the equilibrium structure of the fibril tip and impedes fibril growth in a supersaturated solution. The unraveling of this frustrated state determines the rate of fibril growth. The kinetics of growth of freshly cut fibrils, in which the bulk fibril structure persists at the tip, complemented by molecular simulations, indicate that this frustrated complex comprises three or four monomers in nonnative conformations and likely is contained on the top of a single stack of peptide chains in the fibril structure. This pathway of fibril growth strongly deviates from the common view that the conformational transformation of each captured peptide chain is templated by the previously arrived peptide. The insights into the ensemble structure of the frustrated complex may guide the search for suppressors of Aß fibrillization. The uncovered dynamics of coupled structuring and assembly during fibril growth are more complex than during the folding of most globular proteins, as they involve the collective motions of several peptide chains that are not guided by a funneled energy landscape.

The availability and type of lesbian, gay, bisexual, transgender, and queer content on sperm, oocyte, and embryo provider websites.

PURPOSE: To evaluate and quantify the character and amount of lesbian, gay, bisexual, transgender, and queer (LGBTQ +) content on sperm, oocyte, and embryo provider websites in the USA. METHODS: Websites with LGBTQ + information were categorized into "minimal," "moderate," and "significant" content. The presence and type (category) of LGBTQ + content were assessed in its relationship to geographic regions, in vitro fertilization (IVF) cycles/year, and website types. Interobserver reliability was assessed for the categorization system created. RESULTS: Out of 373 unique websites, 191 (51.2%) had LGBTQ + content of any kind. Regarding the amount of content, websites were categorized as "none" (48.8%), "minimal" (8.0%), "moderate" (28.4%), and "significant" (14.8%). "Private fertility clinic" websites were more likely to have LGBTQ + content and a significantly increased amount of content compared to other website types ("academic hospital" and "sole sperm, oocyte, and embryo provider" websites) (p < 0.0001). Fertility clinics with more IVF cycles/year were more likely to have increased amount of LGBTQ + content compared to those with fewer IVF cycles/year (OR = 4.280; 95% CI, 1.952-9.388). Northeast, West, South, and Midwest regions showed no statistically significant difference in presence and type of content (p = 0.06 and p = 0.13, respectively). CONCLUSION: Approximately half of websites had LGBTQ + content. Private fertility clinics and fertility clinics with increased IVF cycles/year show a positive relationship to the presence and type of LGBTQ + content, while LGBTQ + website content was similar across four geographic regions.

An update on endometriosis biomarkers.

Endometriosis is a debilitating gynecologic disorder characterized by chronic pelvic pain, pelvic adhesions and infertility. The gold standard diagnostic modality is histologically by tissue biopsy, although it can be diagnosed empirically if symptoms improve with medical treatment. A delayed diagnosis of endometriosis often leads to a significant impairment in quality of life and work productivity; hence, significant morbidity has been shown to bear a detrimental impact on society and the economy. The ongoing novel investigation into biomarkers for diagnostic or prognostic evaluation of endometriosis may aid in earlier detection, and thereby, improve patient quality-of-life as well as minimize morbidity. Currently, no single biomarker has been validated for endometriosis; however, there are emerging data on the utility of microRNA for diagnosis and prognosis of disease activity. In this brief review, we will identify and categorize the novel biomarkers for endometriosis.

Impact of time interval from cesarean delivery to frozen embryo transfer on reproductive and neonatal outcomes.

OBJECTIVE: To evaluate differences in reproductive and neonatal outcomes on the basis of the time interval from cesarean delivery to subsequent frozen embryo transfer (FET). DESIGN: Retrospective cohort. SETTING: Multicenter fertility practice. PATIENTS: Women undergoing autologous elective single embryo transfer FET after prior cesarean delivery. INTERVENTION: Time from prior cesarean delivery to subsequent FET. MAIN OUTCOME MEASURES: live birth (LB). RESULTS: A total of 6,556 autologous elective single embryo transfer FET cycles were included. Frozen embryo transfer cycles were divided into eight groups on the basis of the time interval from prior cesarean delivery to subsequent FET in months. A secondary analysis was then performed with time as a continuous variable. The proportion of LBs did not differ significantly across all time interval groups and over continuous time (range: 40.0%-45.6%). The mean gestational age at the time of delivery did not significantly differ as the time between prior cesarean delivery and subsequent FET increased (range: 37.3-38.4). When time was evaluated continuously, the proportion of preterm births was higher with a shorter time between cesarean delivery and subsequent FET. The mean birth weight ranged from 3,181-3,470g, with a statistically significant increase over time. However, the proportions of extremely low birth weight, very low birth weight, and low birth weight did not significantly differ. CONCLUSION: There were no significant differences in reproductive outcomes on the basis of the time interval from cesarean delivery to FET, including LB. The proportion of preterm deliveries decreased with a longer time between cesarean delivery and FET. Differences in mean neonatal birth weight were not clinically significant because the proportion of low birth weight neonates was not significantly different over time. Although large, this sample cannot address all outcomes associated with short interpregnancy intervals, particularly rarer outcomes such as uterine rupture. When counseling patients, the timing of FET after cesarean delivery must be balanced against the risks of increasing maternal age on reproductive and neonatal outcomes.