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BACKGROUND: Individual adverse social determinants of health are associated with increased risk of diabetes in pregnancy, but the relative influence of neighborhood or community-level social determinants of health is unknown. OBJECTIVE: This study aimed to determine whether living in neighborhoods with greater socioeconomic disadvantage, food deserts, or less walkability was associated with having pregestational diabetes and developing gestational diabetes. STUDY DESIGN: We conducted a secondary analysis of the prospective Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be. Home addresses in the first trimester were geocoded at the census tract level. The exposures (modeled separately) were the following 3 neighborhood-level measures of adverse social determinants of health: (1) socioeconomic disadvantage, defined by the Area Deprivation Index and measured in tertiles from the lowest tertile (ie, least disadvantage [T1]) to the highest (ie, most disadvantage [T3]); (2) food desert, defined by the United States Department of Agriculture Food Access Research Atlas (yes/no by low income and low access criteria); and (3) less walkability, defined by the Environmental Protection Agency National Walkability Index (most walkable score [15.26-20.0] vs less walkable score [

The role of parathyroid hormone (PTH)-related protein (PTHrP) in breast cancer remains controversial, with reports of PTHrP inhibiting or promoting primary tumor growth in preclinical studies. Here, we provide insight into these conflicting findings by assessing the role of specific biological domains of PTHrP in tumor progression through stable expression of PTHrP (-36-139aa) or truncated forms with deletion of the nuclear localization sequence (NLS) alone or in combination with the C-terminus. Although the full-length PTHrP molecule (-36-139aa) did not alter tumorigenesis, PTHrP lacking the NLS alone accelerated primary tumor growth by downregulating p27, while PTHrP lacking the NLS and C-terminus repressed tumor growth through p27 induction driven by the tumor suppressor leukemia inhibitory factor receptor (LIFR). Induction of p27 by PTHrP lacking the NLS and C-terminus persisted in bone disseminated cells, but did not prevent metastatic outgrowth, in contrast to the primary tumor site. These data suggest that the PTHrP NLS functions as a tumor suppressor, while the PTHrP C-terminus may act as an oncogenic switch to promote tumor progression through differential regulation of p27 signaling. [ABSTRACT FROM AUTHOR]

Select Drug Category Opiates/Opioids Topic Tolerance/Dependence Abstract Detail Clinical - Epidemiology Abstract Category Original Research Characterize the relationship between intraoperative opioid administration and postoperative pain and opioid requirements. We conducted a retrospective cohort study of 61,250 adult patients who received non-cardiac surgery under general anesthesia at a quaternary care center between 2016 and 2020. The exposure variable was intraoperative fentanyl and intraoperative hydromorphone average effect site concentration. The primary study outcomes were maximal pain score during post-anesthesia care unit (PACU) stay and cumulative opioids administered in the PACU in morphine milligram equivalents (MME). Secondary outcomes included frequency of uncontrolled pain at 24 hours, new instances of chronic pain diagnosis, total opioid use at 24 hours and in-hospital, opioid prescriptions at 30, 90, and 180 postoperative days, frequency of new persistent opioid use, maximal pain score in the first 24 hours and in-hospital, and incidence of opioid related complications in PACU. We used multivariate propensity weighting to control for confounding and estimated the counterfactual difference in outcomes after administration of an additional 100 mcg fentanyl or 500 mcg hydromorphone intraoperatively. Increased intraoperative fentanyl and intraoperative hydromorphone were both associated with reduced maximum pain scores in the PACU. Both exposures were also associated with a reduced probability and reduced total dosage of opioid administration in the PACU. We found that increased fentanyl administration in particular was associated with lower frequency of uncontrolled pain, decreased chronic pain at 3-months, fewer opioid prescriptions at 30-, 90-, and 180-days, and decreased persistent opioid use, without significant increases in side effects. Our results show that intraoperative opioid administration is significantly associated with short- and long-term effects on post-operative pain and opioid outcomes. Contrary to prevailing trends, reduced opioid administration during surgery may have the unintended consequence of increasing postoperative pain and opioid consumption. Our analysis suggests that significant improvements in long-term outcomes might be achieved by optimizing opioid administration during surgery. [ABSTRACT FROM AUTHOR]