Key Questions and Gaps in Understanding Adipose Tissue Macrophages and Early-Life Metabolic Programming.

The global obesity epidemic, with its associated comorbidities and increased risk of early mortality, underscores the urgent need for enhancing our understanding of the origins of this complex disease. It is increasingly clear that metabolism is programmed early in life and that metabolic programming can have life-long health consequences. As a critical metabolic organ sensitive to early-life stimuli, proper development of adipose tissue (AT) is crucial for life-long energy homeostasis. Early-life nutrients, especially fatty acids (FA), significantly influence the programming of AT and shape its function and metabolism. Of growing interest are the dynamic responses during pre- and postnatal development to proinflammatory omega-6 (n6) and anti-inflammatory omega-3 (n3) FA exposures in AT. In the US maternal diet, the ratio of 'pro-inflammatory' n6- to 'anti-inflammatory' n3-FA has grown dramatically due to the greater prevalence of n6-FA. Notably, AT macrophages (ATM) form a significant population within adipose stromal cells, playing not only an instrumental role in AT formation and maintenance, but also acting as key mediators of cell-to-cell lipid and cytokine signaling. Despite rapid advances in ATM and immunometabolism fields, research has focused on responses to obesogenic diets and during adulthood. Consequently, there is a significant gap in identifying the mechanisms contributing metabolic health, especially regarding lipid exposures during the establishment of ATM physiology. Our review highlights the current understanding of ATM diversity, their critical role in AT, and their potential role in early-life metabolic programming, as well as the broader implications for metabolism and health.

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.

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.

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.

NR2F2 Reactivation in Early-life Adipocyte Stem-like Cells Rescues Adipocyte Mitochondrial Oxidation.

In humans, perinatal exposure to an elevated omega-6 (n6) relative to omega-3 (n3) Fatty Acid (FA) ratio is associated with the likelihood of childhood obesity. In mice, we show perinatal exposure to excessive n6-FA programs neonatal Adipocyte Stem-like cells (ASCs) to differentiate into adipocytes with lower mitochondrial nutrient oxidation and a propensity for nutrient storage. Omega-6 FA exposure reduced fatty acid oxidation (FAO) capacity, coinciding with impaired induction of beige adipocyte regulatory factors PPARγ, PGC1α, PRDM16, and UCP1. ASCs from n6-FA exposed pups formed adipocytes with increased lipogenic genes in vitro, consistent with an in vivo accelerated adipocyte hypertrophy, greater triacylglyceride accumulation, and increased % body fat. Conversely, n6-FA exposed pups had impaired whole animal 13 C-palmitate oxidation. The metabolic nuclear receptor, NR2F2, was suppressed in ASCs by excess n6-FA intake preceding adipogenesis. ASC deletion of NR2F2, prior to adipogenesis, mimicked the reduced FAO capacity observed in ASCs from n6-FA exposed pups, suggesting that NR2F2 is required in ASCs for robust beige regulator expression and downstream nutrient oxidation in adipocytes. Transiently re-activating NR2F2 with ligand prior to differentiation in ASCs from n6-FA exposed pups, restored their FAO capacity as adipocytes by increasing the PPARγ-PGC1α axis, mitochondrial FA transporter CPT1A, ATP5 family synthases, and NDUF family Complex I proteins. Our findings suggest that excessive n6-FA exposure early in life dampens an NR2F2-mediated induction of beige adipocyte regulators, resulting in metabolic programming that is shifted towards nutrient storage.

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.

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.