Disparities in osteoarthritis diagnosis and symptoms between English- and Spanish-speaking Latinas over 40 years of age in the United States: a analysis of the Behavioral Risk Factor Surveillance System.

OBJECTIVE: Osteoarthritis (OA) is a prominent musculoskeletal disorder that affects approximately 303 million people worldwide. The challenges that language barriers present to the Latina population in regard to the diagnosis and treatment of OA remain largely unknown. The objective of this study was to examine disparities in the diagnosis and treatment of arthritic conditions in English- and Spanish-speaking Latinas over 40 years of age. DESIGN: We analyzed data from the CDC's Behavioral Risk Screening and Surveillance System (BRFSS), combining the 2017-2020 cycles using sampling weights provided by BRFSS, adjusted for multiple cycles. Determination of English- or Spanish-speaking groups was based on the language of the survey submitted. We calculated population estimates for arthritis diagnosis, physical limitations, and mean joint pain among language groups and by age (40-64 and 65+) and determined associations via odds ratios. RESULTS: Rates of arthritis diagnosis between groups were similar; however we found that Spanish-speaking Latinas 65+ were statistically more likely to report being limited by pain (AOR: 1.55; 95% CI: 1.14-2.09), and among both age groups Spanish-speaking Latinas reported higher pain scores than the English-speaking group (40-64 age group: Coef: 0.74, SE = 0.14, P < .001; 65 + age group: Coef: 1.05, SE = 0.2, P < .001). CONCLUSION: Results from this study show that while there were no significant differences in rates of diagnosis, Spanish-speaking Latinas were more likely to be limited by joint pain and report higher pain scores.

Switching the intracellular pathway and enhancing the therapeutic efficacy of small interfering RNA by auroliposome.

Gene silencing using small-interfering RNA (siRNA) is a viable therapeutic approach; however, the lack of effective delivery systems limits its clinical translation. Herein, we doped conventional siRNA-liposomal formulations with gold nanoparticles to create "auroliposomes," which significantly enhanced gene silencing. We targeted MICU1, a novel glycolytic switch in ovarian cancer, and delivered MICU1-siRNA using three delivery systems-commercial transfection agents, conventional liposomes, and auroliposomes. Low-dose siRNA via transfection or conventional liposomes was ineffective for MICU1 silencing; however, in auroliposomes, the same dose gave >85% gene silencing. Efficacy was evident from both in vitro growth assays of ovarian cancer cells and in vivo tumor growth in human ovarian cell line-and patient-derived xenograft models. Incorporation of gold nanoparticles shifted intracellular uptake pathways such that liposomes avoided degradation within lysosomes. Auroliposomes were nontoxic to vital organs. Therefore, auroliposomes represent a novel siRNA delivery system with superior efficacy for multiple therapeutic applications.

DCLK1 is a broadly dysregulated target against epithelial-mesenchymal transition, focal adhesion, and stemness in clear cell renal carcinoma.

Renal clear cell carcinoma (RCC) is the most common type of kidney cancer and the 8th most common cancer overall in the US. RCC survival rates drop precipitously with regional and distant spread and recent studies have demonstrated that RCC presents an epithelial-mesenchymal transition (EMT) phenotype linked to increased recurrence and decreased survival. EMT is a key characteristic of tumor stem cells (TSCs) along with chemo-resistance and radio-resistance, which are also phenotypic of RCC. Targeting these factors is key to increasing the survival of RCC patients. Doublecortin-like kinase 1 (DCLK1) marks TSCs in pancreatic and colorectal cancer and regulates EMT and stemness. Analysis of the Cancer Genome Atlas' RCC dataset revealed that DCLK1 is overexpressed and dysregulated on the mRNA and epigenetic level in more than 93% of RCC tumors relative to adjacent normal tissue. Immunohistochemistry using α-DCLK1 antibody confirmed overexpression and demonstrated a major increase in immunoreactivity in stage II-III tumors compared to normal kidney and stage I tumors. Small-interfering RNA (siRNA) mediated knockdown of DCLK1 resulted in decreased expression of EMT and pluripotency factors and significantly reduced invasion, migration, focal adhesion, drug-resistance, and clonogenic capacity. These findings suggest that DCLK1 is a novel, overexpressed factor in RCC progression that may be targeted to suppress EMT, metastasis, and stemness in early-stage and advanced RCC to increase patient survival. Moreover, the possibility that DCLK1 may mark a population of tumor stem-like cells in RCC should be further investigated in light of these findings.

DCLK1 facilitates intestinal tumor growth via enhancing pluripotency and epithelial mesenchymal transition.

Doublecortin-like kinase 1 (Dclk1) is overexpressed in many cancers including colorectal cancer (CRC) andit specifically marks intestinal tumor stem cells. However, the role of Dclk1 in intestinal tumorigenesis in Apc mutant conditions is still poorly understood. We demonstrate that Dclk1 expression and Dclk1+ cells are significantly increased in the intestinal epithelium of elderly ApcMin/+ mice compared to young ApcMin/+ mice and wild type mice. Intestinal epithelial cells of ApcMin/+ mice demonstrate increased pluripotency, self-renewing ability, and EMT. Furthermore, miRNAs are dysregulated, expression of onco-miRNAs are significantly increased with decreased tumor suppressor miRNAs. In support of these findings, knockdown of Dclk1 in elderly ApcMin/+ mice attenuates intestinal adenomas and adenocarcinoma by decreasing pluripotency, EMT and onco-miRNAs indicating that Dclk1 overexpression facilitates intestinal tumorigenesis. Knocking down Dclk1 weakens Dclk1-dependent intestinal processes for tumorigenesis. This study demonstrates that Dclk1 is critically involved in facilitating intestinal tumorigenesis by enhancing pluripotency and EMT factors in Apc mutant intestinal tumors and it also provides a potential therapeutic target for the treatment of colorectal cancer.