Social-geographic disparities in suicidal ideations among methamphetamine users in the USA.

IMPORTANCE: Methamphetamine use is a growing public health concern nationwide. Suicide is the second leading cause of death in 2019 for US citizens aged 10-14 years and 25-34 years and is also a significant public health concern. Understanding the intersection of methamphetamine use and suicidal ideation (SI) is necessary to develop public health and policy solutions that mitigate these ongoing severe public health issues. OBJECTIVE: Our objective was to examine SI in methamphetamine users to allow us to determine prevalence and trends by age, sex, race, and geographical region. DESIGN, SETTINGS, AND PARTICIPANTS: Using data collected between 2008 and 2019 from the National Inpatient Sample (NIS) database, we identified hospital admissions (HA) of patients ≥18 years of age with a primary or secondary diagnosis of SI who were also diagnosed as methamphetamine users. Those who used other substances with methamphetamine were excluded from the analysis. MAIN OUTCOME AND MEASURES: To determine the trend and prevalence of hospital admissions due to SI and SI among methamphetamine users, we used trend weights to calculate the national estimates and performed design-based analysis to account for complex survey design and sampling weights on data collected between 2008 and 2019 in the US. RESULTS: The prevalence ratio (PR) of hospitalizations with concurrent SI and methamphetamine use increased 16-fold from 2008 to 2019. The most significant increase occurred between 2015 and 2016; the PR doubled from 6.07 to 12.14. The PR of hospitalizations with concurrent SI and methamphetamine use was highest in patients aged 26-40 (49.08%) and 41-64 (28.49%). Patients aged 41-64 showed the most significant increase from 2008 to 2019 (15.8-fold). While non-Hispanic White patients comprised most of these hospitalizations (77.02%), non-Hispanic Black patients showed the highest proportional increase (39.1-fold). The Southern and Western regions in the US showed the highest PR for these hospitalizations (34.86% and 34.31%, respectively). CONCLUSION AND RELEVANCE: Our findings indicate that SI in methamphetamine users has been increasing for some time and is likely to grow. In addition, our results suggest that these patients are demographically different. Both conditions are associated with a lesser likelihood of seeking and receiving care. Therefore, when addressing increased SI or methamphetamine use, learning more about patients who share both conditions is necessary to ensure proper care.

Breast Cancer-Stromal Interactions: Adipose-Derived Stromal/Stem Cell Age and Cancer Subtype Mediated Remodeling.

Adipose tissue is characterized as an endocrine organ that acts as a source of hormones and paracrine factors. In diseases such as cancer, endocrine and paracrine signals from adipose tissue contribute to cancer progression. Young individuals with estrogen receptor-alpha positive (ER-α+) breast cancer (BC) have an increased resistance to endocrine therapies, suggesting that alternative estrogen signaling is activated within these cells. Despite this, the effects of stromal age on the endocrine response in BC are not well defined. To identify differences between young and aged ER-α+ breast tumors, RNA sequencing data were obtained from The Cancer Genome Atlas. Analysis revealed enrichment of matrix and paracrine factors in young (≤40 years old) patients compared to aged (≥65 years old) tumor samples. Adipose-derived stromal/stem cells (ASCs) from noncancerous lipoaspirate of young and aged donors were evaluated for alterations in matrix production and paracrine secreted factors to determine if the tumor stroma could alter estrogen signaling. Young and aged ASCs demonstrated comparable proliferation, differentiation, and matrix production, but exhibited differences in the expression levels of inflammatory cytokines (Interferon gamma, interleukin [IL]-8, IL-10, Tumor necrosis factor alpha, IL-2, and IL-6). Conditioned media (CM)-based experiments showed that young ASC donor age elevated endocrine response in ER-α+ BC cell lines. MCF-7 ER-α+ BC cell line treated with secreted factors from young ASCs had enhanced ER-α regulated genes (PGR and SDF-1) compared to MCF-7 cells treated with aged ASC CM. Western blot analysis demonstrated increased activation levels of p-ER ser-167 in the MCF-7 cell line treated with young ASC secreted factors. To determine if ER-α+ BC cells heightened the cytokine release in ASCs, ASCs were stimulated with MCF-7-derived CM. Results demonstrated no change in growth factors or cytokines when treated with the ER-α+ secretome. In contrast to ER-α+ CM, the ER-α negative MDA-MB-231 derived CM demonstrated increased stimulation of pro-inflammatory cytokines in ASCs. While there was no observed change in the release of selected paracrine factors, MCF-7 cells did induce matrix production and a pro-adipogenic lineage commitment. The adipogenesis was evident by increased collagen content through Sirius Red/Fast Green Collagen stain, lipid accumulation evident by Oil Red O stain, and significantly increased expression in PPARγ mRNA expression. The data from this study provide evidence suggesting more of a subtype-dependent than an age-dependent difference in stromal response to BC, suggesting that this signaling is not heightened by reciprocal signals from ER-α+ BC cell lines. These results are important in understanding the mechanisms of estrogen signaling and the dynamic and reciprocal nature of cancer cell-stromal cell crosstalk that can lead to tumor heterogeneity and variance in response to therapy.