Targeting aberrant fatty acid synthesis and storage in endocrine resistant breast cancer cells.

Background: Lipid metabolic reprogramming is an emerging characteristic of endocrine therapy (ET) resistance in estrogen receptor-positive (ER+) breast cancer. We explored changes in lipid metabolism in ER+ breast cancer cell lines following acquired resistance to common endocrine treatments and tested efficacy of an inhibitor in current clinical trials. Methods: We derived ER+ breast cancer cell lines resistant to Tamoxifen (TamR), Fulvestrant (FulvR), and long-term estrogen withdrawal (EWD). Parental and ET resistant cells were subjected to global gene expression and unbiased lipidomic profiling. Lipid storage changes were assessed via neutral lipid staining with Oil Red O (ORO). The impact of the fatty acid synthase (FASN) inhibitor TVB-2640 on the growth and lipid storage of these cell lines was evaluated. Additionally, 13 C 2 -acetate tracing was used to examine FASN activity in parental and ET resistant cells in the absence or presence of TVB-2640. Results: Compared to parental cells, lipid metabolism and processing pathways were notably enriched in ET resistant cells, which exhibited distinct lipidomes characterized by increased triglyceride and polyunsaturated FA (PUFA) species. ET-resistant cells displayed enhanced cytoplasmic lipid droplets. Increased FASN protein levels were observed in ET-resistant cells, and TVB-2640 effectively inhibited FASN activity. FASN inhibition reduced cell growth in some but not all cell lines and ET resistance types and did not correlate to lipid storage reduction. 13 C 2 -acetate tracing confirmed reduced palmitate synthesis and enhanced PUFA synthesis in ET-resistant cells, especially when combined with FulvR. Conclusion: ET resistant breast cancer cells exhibit a shift towards enhanced triglyceride storage and complex lipids enriched with PUFA acyl chains. While targeting FASN alongside ET may not fully overcome ET resistance in our models, focusing on the unique lipid metabolic dependencies, such as PUFA pathways, may present a promising alternative strategy for treating ET resistant breast cancer.

Laparoscopic Diagnosis and Treatment of an Isolated Cervical Diverticulum.

BACKGROUND: Congenital müllerian anomalies are found in 8.0% of women with infertility and up to 5.5% of women in a general population. Cervical diverticulum is a type of cervical malformation that can be congenital or acquired, with only select cases documented in the literature. Cervical diverticulum can be asymptomatic or present with abnormal uterine bleeding, pelvic pain, or infertility. Previously described management options are largely limited to observation or exploratory laparotomy. CASE: A 35-year-old woman, gravida 2 para 2, presented with persistent menorrhagia, pelvic pain, and abdominal bloating and was found to have an 8-cm right adnexal mass on pelvic ultrasonography. Magnetic resonance imaging showed a hemorrhagic cervical mass communicating with the uterine cavity. The mass was resected laparoscopically, and pathology revealed fibromuscular tissue with endocervical epithelium consistent with a cervical diverticulum. CONCLUSION: Isolated cervical diverticula are rare but should be considered in the differential diagnosis of adnexal masses. Laparoscopic surgery is a safe, minimally invasive approach for evaluation and repair of cervical diverticula.

Advances in Imaging of Inflammation, Fibrosis, and Cancer in the Gastrointestinal Tract.

Gastrointestinal disease is prevalent and broad, manifesting itself in a variety of ways, including inflammation, fibrosis, infection, and cancer. However, historically, diagnostic technologies have exhibited limitations, especially with regard to diagnostic uncertainty. Despite development of newly emerging technologies such as optoacoustic imaging, many recent advancements have focused on improving upon pre-existing modalities such as ultrasound, computed tomography, magnetic resonance imaging, and endoscopy. These advancements include utilization of machine learning models, biomarkers, new technological applications such as diffusion weighted imaging, and new techniques such as transrectal ultrasound. This review discusses assessment of disease processes using imaging strategies for the detection and monitoring of inflammation, fibrosis, and cancer in the context of gastrointestinal disease. Specifically, we include ulcerative colitis, Crohn's disease, diverticulitis, celiac disease, graft vs. host disease, intestinal fibrosis, colorectal stricture, gastric cancer, and colorectal cancer. We address some of the most recent and promising advancements for improvement of gastrointestinal imaging, including unique discussions of such advancements with regard to imaging of fibrosis and differentiation between similar disease processes.

The Green Light for Green Dot: A Qualitative Study of Factors Influencing Adoption of an Efficacious Violence Prevention Program in High School Settings.

The purpose of this qualitative study was to investigate factors influencing the adoption of an effective bystander-based sexual violence prevention intervention. High schools participating in a cluster-randomized controlled trial that found significant declines in sexual violence over time and with full implementation were invited to adopt this program (Green Dot) at no cost. Three emergent themes arose from interviews with 10 intervention implementers. These findings have implications for researchers, practitioners, and high school administrators and may facilitate future program marketing efforts and the development and testing of strategies for targeted dissemination of this and other bystander programs for violence.

Identifying Sleep-Deprived Authors of Tweets: Prospective Study.

BACKGROUND: Social media data can be explored as a tool to detect sleep deprivation. First-year undergraduate students in their first quarter were invited to wear sleep-tracking devices (Basis; Intel), allow us to follow them on Twitter, and complete weekly surveys regarding their sleep. OBJECTIVE: This study aimed to determine whether social media data can be used to monitor sleep deprivation. METHODS: The sleep data obtained from the device were utilized to create a tiredness model that aided in labeling the tweets as sleep deprived or not at the time of posting. Labeled data were used to train and test a gated recurrent unit (GRU) neural network as to whether or not study participants were sleep deprived at the time of posting. RESULTS: Results from the GRU neural network suggest that it is possible to classify the sleep-deprivation status of a tweet's author with an average area under the curve of 0.68. CONCLUSIONS: It is feasible to use social media to identify students' sleep deprivation. The results add to the body of research suggesting that social media data should be further explored as a potential source for monitoring health.

Piloting CenteringParenting in Two Alberta Public Health Well-Child Clinics.

OBJECTIVES: To pilot a group health service delivery model, CenteringParenting, for new parents, to assess its feasibility and impact on maternal and infant outcomes. DESIGN AND SAMPLE: Families attended six, 2-hr group sessions in their child's first year of life with three to seven other families. Health assessments, parent-led discussions, and vaccinations occurred within the group. MEASURES: Demographic, breastfeeding, vaccination, maternal psychosocial health, parenting, and satisfaction data were collected and compared to a representative cohort. RESULTS: Four groups ran in two clinics. Four to eight parent/infant dyads participated in each group, 24 total dyads. Most participating parents were mothers. Dyads in the group model received 12 hr of contact with Public Health over the year compared to 3 hr in the typical one-on-one model. Participants were younger, more likely to have lower levels of education, and lower household income than the comparison group. Parents reported improvements in parenting experiences following the program. At 4 months, all CenteringParenting babies were vaccinated compared to 95% of babies in the comparison group. CONCLUSIONS: The pilot was successfully completed. Additional research is required to examine the effectiveness of CenteringParenting. Data collected provide insight into potential primary outcomes of interest and informs larger, rigorously designed longitudinal studies.