Nkx2.5 is essential to establish normal heart rate variability in the zebrafish embryo.

Heart rate variability (HRV) has become an important clinical marker of cardiovascular health and a research measure for the study of the cardiac conduction system and its autonomic controls. While the zebrafish (Danio rerio) is an ideal vertebrate model for understanding heart development, HRV has only recently been investigated in this system. We have previously demonstrated that nkx2.5 and nkx2.7, two homologues of Nkx2-5 expressed in zebrafish cardiomyocytes, play vital roles in maintaining cardiac chamber-specific characteristics. Given observed defects in ventricular and atrial chamber identities in nkx2.5-/- embryos coupled with conduction system abnormalities in murine models of Nkx2.5 insufficiency, we postulated that reduced HRV would serve as a marker of poor cardiac health in nkx2.5 mutants and in other zebrafish models of human congenital heart disease. Using live video image acquisition, we derived beat-to-beat intervals to compare HRV in wild-type and nkx2.5-/- embryos. Our data illustrate that the nkx2.5 loss-of-function model exhibits increased heart rate and decreased HRV when compared with wild type during embryogenesis. These findings validate HRV analysis as a useful quantitative tool for assessment of cardiac health in zebrafish and underscore the importance of nkx2.5 in maintaining normal heart rate and HRV during early conduction system development.

Racial Disparities in Survival Outcomes of Patients With Serous Epithelial Ovarian Cancer: A Retrospective Cohort Analysis.

OBJECTIVE: To identify racial disparities in five-year survival rates in women affected by serous epithelial ovarian carcinoma in the United States (US). METHODS: This retrospective cohort study analyzed data from the 2010 to 2016 Surveillance, Epidemiology, and End Results (SEER) program database. Women with a primary malignancy of serous epithelial ovarian carcinoma, using International Classification of Diseases for Oncology (ICD-O) Topography Coding and ICD-O-3 Histology Coding, were included in this study. Race and ethnicity were combined into the following groups: Non-Hispanic White (NHW), Non-Hispanic Black (NHB), Non-Hispanic Asian/Pacific Islander (NHAPI), Non-Hispanic Other (NHO), and Hispanics. Cancer-specific survival was measured at five years post-diagnosis. A comparison of baseline characteristics was assessed using Chi-squared tests. Unadjusted and adjusted Cox regression models were used to calculate hazard ratios (HR) and corresponding 95% confidence intervals (CI). RESULTS: From 2010 to 2016, there were 9,630 women with a primary diagnosis of serous ovarian carcinoma identified in the SEER database. A higher proportion of Asian/PI women (90.7%) were diagnosed with high-grade malignancy (poorly differentiated/undifferentiated) compared to NHW women (85.4%). NHB women (9.7%) were less likely to undergo surgery when compared to NHW women (6.7%). Hispanic women had the highest proportion of uninsured women (5.9%), while NHW and NHAPI had the lowest (2.2% each). A higher proportion of NHB (74.2%) and Asian/PI (71.3%) women presented with the distant disease compared to NHW women (70.2%). After adjustment for age, insurance, marital status, stage, metastases, and surgical resection, NHB women had the highest hazard of death within five years compared to NHW women (adjusted (adj) HR 1.22, 95% CI 1.09-1.36, p<0.001). Hispanic women also had lower five-year survival probabilities compared to NHW women (adj HR 1.21, 95% CI 1.12-1.30, p<0.001). Patients undergoing surgery had significantly increased survival probability compared to those who did not (p<0.001). As expected, women with Grade III and Grade IV disease both had significantly lower five-year survival probabilities compared to Grade I (p<0.001). CONCLUSION: This study reveals that there is an association between race and overall survival in patients with serous ovarian carcinoma, with NHB and Hispanic women having the highest hazards of death compared to NHW women. This adds to the existing body of literature as survival outcomes in Hispanic patients relative to NHW patients are not well documented. Because of the potential interplay between overall survival and several factors including race, future studies should aim to investigate other socioeconomic factors that may be impacting survival.

Racial and Ethnic Inequality in Survival Outcomes of Women With Triple Negative Breast Cancer.

Purpose Triple-negative breast cancer (TNBC) is the most lethal group of breast cancers. Socioeconomic factors may contribute to differences in survival rates. This study aims to identify racial/ethnic disparities in five-year survival rates among women affected by TNBC in the United States. Methods This retrospective study analyzed data from the 2010-2016 Surveillance, Epidemiology, and End Results Program database. Patients with a primary malignancy of triple-negative breast cancer were included in this study. Cancer-specific survival was measured at five years post-diagnosis. Cox regression models were used to calculate hazard ratios (HR) and corresponding 95% confidence intervals (CI). Results From 2010-2016, there were 26,963 women with a primary diagnosis of TNBC. After adjustment for age, insurance, marital status, stage, and surgery type, Hispanic women had the highest hazard of death when compared to White women (adjusted (adj) HR, 1.14, p<0.001). Further, non-Hispanic Black women also had a lower survival probability when compared to White women (adj HR, 1.06, p=0.002). Conclusion This study reveals that Hispanic women had the highest hazard of death when compared to White women. As TNBC is the most fatal breast cancer, future studies should investigate socioeconomic factors that may worsen prognosis of this disease.