Background: Genomic instability and chemoresistance can arise in cancer due to a unique form of plasticity: that of polyploid giant cancer cells (PGCCs). These cells form under the stress of chemotherapy and have higher than diploid chromosome content. PGCCs are able to then repopulate tumors through an asymmetric daughter cell budding process. PGCCs have been observed in ovarian cancer histology, including the deadly and common form high-grade serous ovarian carcinoma (HGSC). We previously discovered that drugs which disrupt the cellular recycling process of autophagy are uniquely efficacious in pre-clinical HGSC models. While autophagy induction has been associated with PGCCs, it has never been previously investigated if autophagy modulation interacts with the PGCC life cycle and this form of tumor cell plasticity. Methods: CAOV3 and OVCAR3 ovarian cancer cell lines were treated with carboplatin or docetaxel to induce PGCC formation. Microscopy was used to characterize and quantify PGCCs formed by chemotherapy. Two clinically available drugs that inhibit autophagy, hydroxychloroquine and nelfinavir, and a clinically available activator of autophagy, rapamycin, were employed to test the effect of these autophagy modulators on PGCC induction and subsequent colony formation from PGCCs. Crystal violet-stained colony formation assays were used to quantify the tumor-repopulating stage of the PGCC life cycle. Results: Autophagy inhibitors did not prevent PGCC formation in OVCAR3 or CAOV3 cells. Rapamycin did not induce PGCC formation on its own nor did it exacerbate PGCC formation by chemotherapy. However, hydroxychloroquine prevented efficient colony formation in CAOV3 PGCCs induced by carboplatin (27% inhibition) or docetaxel (41% inhibition), as well as in OVCAR3 cells (95% and 77%, respectively). Nelfinavir similarly prevented colony formation in CAOV3 PGCCs induced by carboplatin (64% inhibition) or docetaxel (94% inhibition) as well as in OVCAR3 cells (89% and 80%, respectively). Rapamycin surprisingly also prevented PGCC colony outgrowth (52–84% inhibition). Conclusions: While the autophagy previously observed to correlate with PGCC formation is unlikely necessary for PGCCs to form, autophagy modulating drugs severely impair the ability of HGSC PGCCs to form colonies. Clinical trials which utilize hydroxychloroquine, nelfinavir, and/or rapamycin after chemotherapy may be of future interest.

Background/Objectives: Stress during pregnancy critically impacts maternal and fetal health. While prior research has linked sociodemographic and biological factors to stress levels, the role of specific biomarkers, such as vitamin D (VD), remains unexplored. This study examined the relationships among sociodemographic factors, VD status (as measured by serum 25-hydroxyvitamin D [25(OH)D] concentration), and perceived stress in pregnant women. We hypothesized that 25(OH)D concentration would be associated with perceived stress levels during pregnancy. Methods: A post hoc analysis of the Kellogg Pregnancy VD study was conducted on a cohort of 232 pregnant women with Perceived Stress Scale (PSS-10) scores at months 2, 5, and 7 with corresponding 25(OH)D concentrations. PSS-10 scores were classified into two groups: patients with scores of 0–13 were considered to have low stress, while those with scores of 14–40 were considered to have moderate-to-high stress. Logistic regression models identified factors associated with moderate-to-high stress. Results: At month 2, univariate analyses showed that being married (p = 0.002), having a college education (p = 0.0013), and lower BMI (p = 0.018) were associated with lower perceived stress, whereas Black race was associated with higher perceived stress (p = 0.027). By month 7, higher serum 25(OH)D concentration was the only significant predictor of perceived stress in univariate analysis (p = 0.002). In multivariate models at month 7, 25(OH)D approached significance (p = 0.053). Conclusions: Early in pregnancy, race, marital status, college education, and BMI were significantly associated with PSS-10 score. By month 7, 25(OH)D concentration over time emerged as a factor that was significantly associated in univariate analysis and showed a trend toward significance in multivariate models. VD status, as measured by 25(OH)D concentration, may act as a biomarker of stress during pregnancy. Results warrant further study in prospective intervention trials.

Objective: Investigate the association between vitamin D status (as measured by 25-hydroxyvitamin D concentration [25(OH)D]) and gestational age at delivery. Study design: This was a retrospective chart review of electronic medical records ( n = 15,506) from women delivering at the Medical University of South Carolina, with first maternal 25(OH)D concentrations measured from January 2016 to March 2024. Result: Women delivering <37 weeks ( n = 1652; 31.3 ± 17.8 ng/mL) had lower 25(OH)D concentrations compared to those delivering at 37 weeks or later ( n = 13,451; 34.8 ± 17.3 ng/mL), with a mean difference of –3.46 ng/mL (95% Confidence Interval (CI): –4.54 to –2.38, p < 0.0001). This difference was even more pronounced among women delivering before 32 weeks ( n = 385; 26.2 ± 14.9 ng/mL), who had substantially lower 25(OH)D concentrations than term deliveries, with a mean difference of –8.56 ng/mL (95% CI: –10.70 to –6.42, p < 0.0001). Conclusion: Maternal vitamin D status was associated with gestational age at delivery. Lower maternal 25(OH)D concentrations were observed among women who delivered preterm compared with those delivering at term. These findings suggest a potential relationship between vitamin D status and preterm birth and support further research into whether optimizing vitamin D status during pregnancy may improve perinatal outcomes.

Burn injuries can cause lasting functional impairment, often requiring formal impairment ratings for workers’ compensation cases. Cutaneous functional units (CFUs), which represent skin areas involved in single-joint motion, may better capture functional impact than TBSA, yet they are not included in current impairment rating guidelines. This study evaluated relationships between initial TBSA, initial CFUs, final scar CFUs, and impairment ratings, hypothesizing that scar burden measured by CFUs would be strongly associated with impairment. A retrospective review was conducted for 78 burn patients with photographically documented TBSA and whole-body impairment ratings at maximum medical improvement at The South Carolina Burn Center at the Medical University of South Carolina. Initial CFUs were calculated from injury photographs using a previously established CFU map, and scar CFUs were calculated from scar photographs obtained at the time of impairment rating. Associations between TBSA, CFUs, and impairment ratings were assessed using Spearman’s rho. Initial TBSA was significantly correlated with initial CFUs (rho = 0.471, P < .001) and more strongly correlated with scar CFUs (rho = 0.541, P < .001). Initial TBSA was also significantly correlated with impairment ratings (rho = 0.418, P = .002). Both initial CFUs (rho = 0.307, P = .006) and scar CFUs (rho = 0.569, P < .001) were significantly associated with impairment, with scar CFUs demonstrating the strongest relationship. These findings suggest that scar CFUs may represent a clinically relevant correlate of impairment ratings and warrant further prospective evaluation.