Bisphenol A (BPA) is an endocrine disruptor with estrogenic properties that can adversely affect meiotic spindle assemblies. Our data indicate that BPA exposure in female patients may interfere with ...oocyte quality during IVF, as suggested by the inverse association between serum unconjugated BPA concentration and normal fertilization.
Antibody class-switch DNA recombination (CSR) is initiated by AID-introduced DSBs in the switch (S) regions targeted for recombination, as effected by Ku70/Ku86-mediated NHEJ. Ku-deficient B cells, ...however, undergo (reduced) CSR through an alternative(A)-NHEJ pathway, which introduces microhomologies in S-S junctions. As microhomology-mediated end-joining requires annealing of single-strand DNA ends, we addressed the contribution of single-strand annealing factors HR Rad52 and translesion DNA polymerase θ to CSR. Compared with their Rad52
counterparts, which display normal CSR, Rad52
B cells show increased CSR, fewer intra-Sμ region recombinations, no/minimal microhomologies in S-S junctions, decreased c-Myc/IgH translocations and increased Ku70/Ku86 recruitment to S-region DSB ends. Rad52 competes with Ku70/Ku86 for binding to S-region DSB ends. It also facilitates a Ku-independent DSB repair, which favours intra-S region recombination and mediates, particularly in Ku absence, inter-S-S recombination, as emphasized by the significantly greater CSR reduction in Rad52
versus Rad52
B cells on Ku86 knockdown.
•We fed pregnant mice BPA at 5–50,000μg/kg/day and studied adult male offspring.•Low dose BPA-treated males showed adipocyte hyperplasia and greater fat mass.•Low dose BPA-treated males had reduced ...glucose tolerance and serum adiponectin.•Most outcomes had non-monotonic dose responses.•Control and highest-dose BPA groups did not differ for any outcome.
Exposure to bisphenol A (BPA) is implicated in many aspects of metabolic disease in humans and experimental animals. We fed pregnant CD-1 mice BPA at doses ranging from 5 to 50,000μg/kg/day, spanning 10-fold below the reference dose to 10-fold above the currently predicted no adverse effect level (NOAEL). At BPA doses below the NOAEL that resulted in average unconjugated BPA between 2 and 200pg/ml in fetal serum (AUC0–24h), we observed significant effects in adult male offspring: an age-related change in food intake, an increase in body weight and liver weight, abdominal adipocyte mass, number and volume, and in serum leptin and insulin, but a decrease in serum adiponectin and in glucose tolerance. For most of these outcomes non-monotonic dose–response relationships were observed; the highest BPA dose did not produce a significant effect for any outcome. A 0.1-μg/kg/day dose of DES resulted in some but not all low-dose BPA outcomes.
Mental health concerns are on the rise among youth, contributing to a growing need for school-based mental health services. However, challenges to service provision arise due, in part, to workforce ...shortages, service fragmentation, and inefficient allocation of staff time. The current study describes the professional competencies and time allocation of four school-based mental health professions (i.e., school counselors, school psychologists, school social workers, and school nurses) in order to demonstrate how schools can leverage the skills of their existing staff to coordinate a comprehensive approach to support student mental health. First, we identified the core clinical competencies needed to implement the key features of comprehensive school mental health systems. Then, we crosswalked these clinical competencies with the training standards of the four professions. Finally, we conducted a systematic review of the literature to understand how these professionals’ time is allocated, as well as their responsibilities related to the provision of mental health services. Results demonstrated that, although all four professions receive training in most of the core competencies needed to implement comprehensive school mental health services, their skillsets are often underutilized in day-to-day practice. Thus, we concluded that there are at least two untapped opportunities for school leaders to support student mental health—first, maximize the use of school mental health professionals through task-shifting (i.e., reassigning tasks less central to mental health service delivery to other staff), and second, implement an integrated model of school mental health services to efficiently leverage the mental health training of professionals.
Human papillomavirus (HPV) entry into epithelial cells is independent of canonical endocytic pathways. Upon interaction with host cells, HPV establishes infection by traversing through an endocytic ...pathway that is clathrin- and caveolin-independent, but dependent on the annexin A2/S100A10 heterotetramer (A2t). We examined the contribution of monomeric annexin A2 (AnxA2) vs. A2t in HPV infection and endocytosis, and further characterized the role of these molecules in protein trafficking. We specifically show that cell surface A2t is not required for HPV attachment, and in the absence of A2t virion internalization remains clathrin-independent. Without A2t, viral progression from early endosomes to multivesicular endosomes is significantly inhibited, capsid uncoating is dramatically reduced, and lysosomal degradation of HPV is accelerated. Furthermore, we present evidence that AnxA2 forms a complex with CD63, a known mediator of HPV trafficking. Overall, the observed reduction in infection is less significant in the absence of S100A10 alone compared to full A2t, supporting an independent role for monomeric AnxA2. More broadly, we show that successful infection by multiple oncogenic HPV types is dependent on A2t. These findings suggest that A2t is a central mediator of high-risk HPV intracellular trafficking post-entry and pre-viral uncoating.
In 2009, the Joint Commission identified a standardized approach to handoff communication as a patient safety goal to reduce communication errors. Evidence suggests that a structured handoff report, ...combined with active patient participation, reduces communication errors and promotes patient safety. Research shows that bedside handoff increases nurses' accountability by visualizing the patient and exchanging information at the point of care. Based on recommendations from the Joint Commission, the Robert Wood Johnson Foundation, and broader research literature, a standardized approach to bedside handoff and walking rounds was implemented on an inpatient surgical oncology unit. At a Glance • A standardized handoff communication tool is recognized as a Joint Commission patient safety goal to reduce communication errors and improve patient safety. • The benefits of patient safety and satisfaction outweigh the barriers to implementing a bedside handoff report. • A standardized, nurse-driven, electronic report should guide transfer of information during bedside handoff.
Abstract Study Objective Survival into adulthood is now a reality for many adolescents facing cancer. Fertility preservation (FP) is rapidly advancing, but oncology providers and health systems ...struggle to incorporate the newest FP technologies into the clinical care of adolescents. Our objective was to systematically review and synthesize the available data regarding the perspectives, experiences, and preferences of adolescents, parents, and oncology providers about FP to inform clinical implementation of FP technologies. Design, Setting, Participants, Interventions, and Main Outcome Measures Five electronic databases (PubMed, Embase, Web of Knowledge, Cumulative Index to Nursing and Allied Health Literature, PsychInfo) were systematically searched for studies published between January 1999 and May 2014. Adolescents were defined as 12-18 years at the time of diagnosis or designated as pubertal/postpubertal and younger than 18 years of age. Studies were assessed for methodological quality, data were extracted using a standardized form, and results were synthesized using guidelines for a narrative syntheses of quantitative and qualitative data. Results In total, 1237 records were identified, with 22 articles, representing 17 unique studies that met the inclusion criteria. The following topics were consistently observed across studies and populations: (1) fertility in trust; (2) decision-making challenges; (3) provider knowledge and practices; and (4) discrepancies between desired and actual experiences. Conclusion Despite the challenges associated with a new cancer diagnosis, adolescents and parents value the opportunity to discuss fertility concerns and preservation options. Providers play an important role in addressing these topics for families and efforts should be made to incorporate FP discussions into routine cancer care for all adolescents, with attention paid to the unique needs of adolescents and their parents.
PurposeThis study aims to predict popular contributors through text representations of user-generated content in open crowds.Design/methodology/approachThree text representation approaches – count ...vector, Tf-Idf vector, word embedding and supervised machine learning techniques – are used to generate popular contributor predictions.FindingsThe results of the experiments demonstrate that popular contributor predictions are considered successful. The F1 scores are all higher than the baseline model. Popular contributors in open crowds can be predicted through user-generated content.Research limitations/implicationsThis research presents brand new empirical evidence drawn from text representations of user-generated content that reveals why some contributors' ideas are more viral than others in open crowds.Practical implicationsThis research suggests that companies can learn from popular contributors in ways that help them improve customer agility and better satisfy customers' needs. In addition to boosting customer engagement and triggering discussion, popular contributors' ideas provide insights into the latest trends and customer preferences. The results of this study will benefit marketing strategy, new product development, customer agility and management of information systems.Originality/valueThe paper provides new empirical evidence for popular contributor prediction in an innovation crowd through text representation approaches.
OBJECTIVE: To investigate associations between serum bisphenol A (BPA) concentrations and follicular response to exogenous ovary stimulation. DESIGN: Fasting serum was prospectively collected on the ...day of oocyte retrieval and assessed for unconjugated BPA using high-performance liquid chromatography with Coularray detection. Multivariable linear regression and negative binomial regression were used to assess associations between concentrations of BPA and outcome measures. Models were adjusted for race/ethnicity, antral follicle count at baseline, and cigarette smoking. SETTING: A reproductive health center. PATIENT(S): Forty-four women undergoing IVF. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Peak E₂ level and the number of oocytes retrieved during IVF. RESULT(S): The median unconjugated serum BPA concentration is 2.53 ng/mL (range = 0.3–67.36 ng/mL). Bisphenol A is inversely associated with E₂ (β = −0.16; 95% confidence interval = −0.32, 0.01), as well as with E₂ normalized to the number of mature-sized follicles at the hCG trigger (β = −0.14; 95% confidence interval = −0.24, −0.03). No association is observed for BPA and the number of oocytes retrieved (adjusted risk ratio = 0.95; 95% confidence interval = 0.82, 1.10). CONCLUSION(S): Bisphenol A is associated with a reduced E₂ response during IVF. Although limited by the preliminary nature of this study, these results merit confirmation in a future comprehensive investigation.
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