Metformin as a Therapeutic Target in Endometrial Cancers.

Endometrial cancer is the most common gynecologic malignancy in developed countries. Its increasing incidence is thought to be related in part to the rise of metabolic syndrome, which has been shown to be a risk factor for the development of hyperestrogenic and hyperinsulinemic states. This has consequently lead to an increase in other hormone-responsive cancers as well e.g., breast and ovarian cancer. The correlation between obesity, hyperglycemia, and endometrial cancer has highlighted the important role of metabolism in cancer establishment and persistence. Tumor-mediated reprogramming of the microenvironment and macroenvironment can range from induction of cytokines and growth factors to stimulation of surrounding stromal cells to produce energy-rich catabolites, fueling the growth, and survival of cancer cells. Such mechanisms raise the prospect of the metabolic microenvironment itself as a viable target for treatment of malignancies. Metformin is a biguanide drug that is a first-line treatment for type 2 diabetes that has beneficial effects on various markers of the metabolic syndrome. Many studies suggest that metformin shows potential as an adjuvant treatment for uterine and other cancers. Here, we review the evidence for metformin as a treatment for cancers of the endometrium. We discuss the available clinical data and the molecular mechanisms by which it may exert its effects, with a focus on how it may alter the tumor microenvironment. The pleiotropic effects of metformin on cellular energy production and usage as well as intercellular and hormone-based interactions make it a promising candidate for reprogramming of the cancer ecosystem. This, along with other treatments aimed at targeting tumor metabolic pathways, may lead to novel treatment strategies for endometrial cancer

Utilization of a multimodal preoperative pain regimen prior to gynecologic oncology exploratory laparotomies

Objective: The aim of this study was to evaluate the use of a combination of non-opioid preoperative pain medications including Tylenol, Lyrica, and Celecoxib (TLC) in patients undergoing gynecologic oncologic exploratory laparotomies. We evaluated postoperative narcotic use in morphine equvalents (ME) as well as pain scores, anti-emetic use, and length of stay.https://jdc.jefferson.edu/patientsafetyposters/1055/thumbnail.jp

A foundation for provitamin A biofortification of maize: genome-wide association and genomic prediction models of carotenoid levels.

Efforts are underway for development of crops with improved levels of provitamin A carotenoids to help combat dietary vitamin A deficiency. As a global staple crop with considerable variation in kernel carotenoid composition, maize (Zea mays L.) could have a widespread impact. We performed a genome-wide association study (GWAS) of quantified seed carotenoids across a panel of maize inbreds ranging from light yellow to dark orange in grain color to identify some of the key genes controlling maize grain carotenoid composition. Significant associations at the genome-wide level were detected within the coding regions of zep1 and lut1, carotenoid biosynthetic genes not previously shown to impact grain carotenoid composition in association studies, as well as within previously associated lcyE and crtRB1 genes. We leveraged existing biochemical and genomic information to identify 58 a priori candidate genes relevant to the biosynthesis and retention of carotenoids in maize to test in a pathway-level analysis. This revealed dxs2 and lut5, genes not previously associated with kernel carotenoids. In genomic prediction models, use of markers that targeted a small set of quantitative trait loci associated with carotenoid levels in prior linkage studies were as effective as genome-wide markers for predicting carotenoid traits. Based on GWAS, pathway-level analysis, and genomic prediction studies, we outline a flexible strategy involving use of a small number of genes that can be selected for rapid conversion of elite white grain germplasm, with minimal amounts of carotenoids, to orange grain versions containing high levels of provitamin A

Modeling of Tunable Elastic Ultralight Aircraft

Aircraft weight is one of the most critical factors in the design and operation of modern vehicles. The ability to integrate ultra-light materials into the primary load bearing structures has the potential to reduce aircraft weight significantly. Ultralight materials tend to be lattice-based meta-materials that are difficult and computationally expensive to model. One of the advantages of meta-materials is to be able to tune or "program" their bulk material properties through the placement of heterogeneous components in the material. A large amount of time devoted to the simulation in the development time for the tuning of the material can be a barrier to the adoption of large scale lattice materials. In this paper, we present a workflow and analysis tool-set to provide first-order estimates for rapid development of engineered lattice materials for aerospace applications. We present results for estimating the displacement and maximum structural stresses

A locus for inherited focal segmental glomerulosclerosis maps to chromosome 19q13

A locus for inherited focal segmental glomerulosclerosis maps to chromosome 19q13. Rapid Communication. We performed a genome-wide linkage analysis search for a genetic locus responsible for kidney dysfunction in a large family. This inherited condition, characterized by proteinuria, progressive renal insufficiency, and focal segmental glomerulosclerosis, follows autosomal dominant inheritance. We show with a high degree of certainty (maximum 2-point lod score 12.28) that the gene responsible for this condition is located on chromosome 19q13

Gender and age group modified association of dental health indicators with total occlusal force among Korean elders

Background This study aimed to investigate the distribution of objective total occlusal force (TOF) and its association with dental health indicators: dental status, number of natural teeth (NT), natural and rehabilitated teeth, natural posterior teeth (NT-Post), and natural and rehabilitated posterior teeth among Korean elders after controlling for various confounders encompassing socio-demographic factors, behavioral factors and health/oral health factors. Methods This cross-sectional study recruited 551 elders from the Sungbook-Gu health education cohort. TOF was measured using Prescale II as an outcome variable. Dental health indicators assessed by dentists were the main explanatory variables. Analysis of covariance and multivariable linear regression models were applied to evaluate the adjusted association of dental health indicators with TOF. Gender and age group stratified analyses were also applied. Result TOF was higher in dentate elders than denture wearers in males and younger elders. The adjusted mean of TOF and standard error was 464.24 ± 17.15 N for dentate elders, 297.15 ± 28.85 N for partial denture wearers, 280.42 ± 47.71 N for complete denture wearers. Among all dental health indicators, NT-Post showed the highest association with TOF (partial r = 0.330, p < 0.001, R2 = 0.15), followed by NT (partial r = 0.329, p < 0.001, R2 = 0.16). Older elders highlighted the association of NT (partial r = 0.37, p < 0.001, R2 = 0.18). Males decreased the association of NT (partial r = 0.30, p < 0.001, R2 = 0.20) and NT-Post (partial r = 0.29, p < 0.001, R2 = 0.20). Conclusion TOF was significantly associated with dental health indicators, and its association was modified by sex and age group.This study had fnancial support through HDK from the National Research Foundation (NRF) of the Ministry of Science and ICT, Korea (NRF2017M3A9B6062986) and the Korea Centers for Disease Control and Preven‑tion (2018P330400) that did not do anything for the submitted work