No abstract

Ornithine Decarboxylase (ODC) a key enzyme in polyamine biosynthesis is often overexpressed in cancers and contributes to polyamine-induced cell proliferation. We noted ubiquitous expression of ODC1 in our published endometrial cancer gene array data and confirmed this in the cancer genome atlas (TCGA) with highest expression in non-endometrioid, high grade, and copy number high cancers, which have the worst clinical outcomes. ODC1 expression was associated with worse overall survival and increased recurrence in three endometrial cancer gene expression datasets. Importantly, we confirmed these findings using quantitative real-time polymerase chain reaction (qRT-PCR) in a validation cohort of 60 endometrial cancers and found that endometrial cancers with elevated ODC1 had significantly shorter recurrence-free intervals (KM log-rank p = 0.0312, Wald test p = 5.59e-05). Difluoromethylornithine (DFMO) a specific inhibitor of ODC significantly reduced cell proliferation, cell viability, and colony formation in cell line models derived from undifferentiated, endometrioid, serous, carcinosarcoma (mixed mesodermal tumor; MMT) and clear cell endometrial cancers. DFMO also significantly reduced human endometrial cancer ACI-98 tumor burden in mice compared to controls (p = 0.0023). ODC-regulated polyamines (putrescine [Put] and/or spermidine [Spd]) known activators of cell proliferation were strongly decreased in response to DFMO, in both tumor tissue ([Put] (p = 0.0006), [Spd] (p<0.0001)) and blood plasma ([Put] (p<0.0001), [Spd] (p = 0.0049)) of treated mice. Our study indicates that some endometrial cancers appear particularly sensitive to DFMO and that the polyamine pathway in endometrial cancers in general and specifically those most likely to suffer adverse clinical outcomes could be targeted for effective treatment, chemoprevention or chemoprevention of recurrence.

Background and Objectives Benign bone tumors are often treated with extended curettage utilizing an adjuvant therapy to eliminate any remaining tumor cells. The purpose of this study was to explore and compare the histologic depth of necrosis created by various adjuvant therapies used in the treatment of benign bone tumors. Methods A high‐speed burr was utilized to create cortical defects within porcine humeri and femora. Phenol, polymethyl methacrylate (PMMA), argon beam coagulation (ABC), liquid nitrogen, and the Bipolar Hemostatic Sealer (BHS) were each applied to five defects, with an additional five defects left untreated as a control. The maximal depth of necrosis was determined under microscopic examination. Results The phenol, PMMA, ABC, liquid nitrogen, and BHS demonstrated an average histologic depth of necrosis of 0.30, 0.78, 2.54, 2.54, and 0.92 mm, respectively, each of which was significantly increased compared to the control group (p = .001, .003, .003, .01, and  <.001). Their respective variances, a measure of reproducibility, were 0.01, 0.09, 0.96, 1.93, and 0.03 mm2. Conclusion This study confirms, through histologic analysis, adjuvant therapies create a rim of cellular necrosis beyond that of burring during extended curettage, supporting their use in the treatment of benign bone tumors. Furthermore, it provides a head‐to‐head comparison.

Background: Children living near greenhouse agriculture may have an increased risk of pesticide exposure due to drift or direct contact with pesticide-treated areas. However, little is known about whether this increased potential for chronic exposure may impair their neurodevelopment. Methods:We examined 307 children aged 4-9 years, living in agricultural communities in Ecuador (ESPINA study). The two exposures calculated were residential distance from the nearest flower plantation perimeter and flower plantation surface area within 100m of homes. Five neurobehavioral domains were assessed: Attention/Inhibitory Control, Memory/Learning, Visuospatial processing and Sensorimotor (higher values reflect better performance). Low scores were defined according to the test's cut-offs. Models were adjusted for demographic, socioeconomic and growth variables.

Objectives This study aimed to assess current mean serum vitamin C level and prevalence of vitamin C deficiency (serum level &lt;11.4 μmol/L) in the United States using nationally representative data, as well as compare to the previous decade's distributions. The study also explored the predictive effects of demographic variables on prevalence of vitamin C deficiency. Methods The study population included 6740 non-institutionalized civilians aged 6 years and older in the National Health and Nutrition Examination Survey (NHANES) 2017–2018 who represented 274,157,096 individuals in the United States. Multivariable linear and logistic regression analyses were used to test the predictive effects of covariates. Serum vitamin C levels and deficiency prevalence were compared with NHANES 2005–2006 data using Student's t-tests. Results The mean serum vitamin C level was 53.4 μmol/L (95% CI: 50.9, 55.8) and the prevalence of vitamin C deficiency was 5.9% (95% CI: 4.3, 7.6). In multivariable logistic regression analysis accounting for gender, age, race, smoking status, and obesity classification, only current smoking status was associated with deficiency (OR = 3.78 [95% CI: 2.70, 5.29], P = 0.02). Multivariable linear regression of the same factors found that underweight status (P = 0.04) and women (P = 0.02) were associated with higher vitamin C, while smoking status (P = 0.01) and obesity (P = 0.01) were associated with lower level. Although mean serum vitamin C declined from NHANES 2005–2006 to NHANES 2017–2018 (P &lt; 0.05), there was no significant change in deficiency prevalence (P = 0.27). Conclusions In NHANES 2017–2018, mean serum vitamin C level declined, but the prevalence of vitamin C deficiency did not significantly change from that during NHANES 2005–2006. Although gender, smoking status, and weight status were predictive of serum vitamin C level, deficiency was significantly more common only among smokers. These findings suggest that clinicians should continue to be wary of signs and symptoms of vitamin C deficiency and encourage vitamin supplementation when appropriate, particularly with patients who smoke. Funding Sources No funding was required/used for the research.