Discovering Novel Plasma Biomarkers for Ischemic Stroke: Lipidomic and Metabolomic Analyses in an Aged Mouse Model.

Ischemic stroke remains a leading cause of mortality and long-term disability worldwide, necessitating efforts to identify biomarkers for diagnosis, prognosis, and treatment monitoring. The present study aimed to identify novel plasma biomarkers of neurodegeneration and inflammation in a mouse model of stroke induced by distal middle cerebral artery (MCA) occlusion. Using targeted lipidomic and global untargeted metabolomic profiling of plasma collected from aged male mice 24 hours after stroke and weekly thereafter for 7 weeks, we discovered distinct acute and chronic signatures. In the acute phase, we observed elevations in myelin-associated lipids, including sphingomyelin (SM) and hexosylceramide (HCER) lipid species, indicating brain lipid catabolism. In the chronic phase, we identified 12-hydroxyeicosatetraenoic acid (12-HETE) as a putative biomarker of prolonged inflammation, consistent with our previous observation of a biphasic pro-inflammatory response to ischemia in the mouse brain. These results provide insight into the metabolic alterations detectable in the plasma after stroke and highlight the potential of myelin degradation products and arachidonic acid derivatives as biomarkers of neurodegeneration and inflammation, respectively. These discoveries lay the groundwork for further validation in human studies and may improve stroke management strategies.

An Evidence Based Rationale for Health and Wellness Coaching as a Complementary Certification in Undergraduate Health Education.

Health and wellness coaching (HWC) is an effective intervention for many chronic lifestyle diseases. Chronic diseases represent a majority of our severe national healthcare burden. Yet, HWC certification programs vary in delivery method and degree awarded. The purpose of this paper is to provide an evidence based rationale for HWC as a complementary area of study to non-licensure granting, undergraduate health degrees in higher education. A comprehensive review of the literature related to the efficacy of HWC was completed. In addition, the national program directory was mined for descriptive data for approved HWC programs. Given the growing body of support for HWC as an effective intervention, we recommend that institutions deliver HWC curricula as an academic minor for undergraduate students in non-licensure granting health-related degrees to position graduates for entry level careers in HWC. Evidence from the successful deployment of an undergraduate program in HWC supports our contention that HWC be delivered as an academic minor in support of lifestyle health and wellness education. In doing so, the field can offer HWC in a way that is widely accessible to the undergraduate population, while providing a mechanism for direct employment as a professional health and wellness coach.

Interrogating Estrogen Signaling Pathways in Human ER-Positive Breast Cancer Cells Forming Bone Metastases in Mice.

Breast cancer bone metastases (BMET) are incurable, primarily osteolytic, and occur most commonly in estrogen receptor-α positive (ER+) breast cancer. ER+ human breast cancer BMET modeling in mice has demonstrated an estrogen (E2)-dependent increase in tumor-associated osteolysis and bone-resorbing osteoclasts, independent of estrogenic effects on tumor proliferation or bone turnover, suggesting a possible mechanistic link between tumoral ERα-driven osteolysis and ER+ bone progression. To explore this question, inducible secretion of the osteolytic factor, parathyroid hormone-related protein (PTHrP), was utilized as an in vitro screening bioassay to query the osteolytic potential of estrogen receptor- and signaling pathway-specific ligands in BMET-forming ER+ human breast cancer cells expressing ERα, ERß, and G protein-coupled ER. After identifying genomic ERα signaling, also responsibility for estrogen's proliferative effects, as necessary and sufficient for osteolytic PTHrP secretion, in vivo effects of a genomic-only ER agonist, estetrol (E4), on osteolytic ER+ BMET progression were examined. Surprisingly, while pharmacologic effects of E4 on estrogen-dependent tissues, including bone, were evident, E4 did not support osteolytic BMET progression (vs robust E2 effects), suggesting an important role for nongenomic ER signaling in ER+ metastatic progression at this site. Because bone effects of E4 did not completely recapitulate those of E2, the relative importance of nongenomic ER signaling in tumor vs bone cannot be ascertained here. Nonetheless, these intriguing findings suggest that targeted manipulation of estrogen signaling to mitigate ER+ metastatic progression in bone may require a nuanced approach, considering genomic and nongenomic effects of ER signaling on both sides of the tumor/bone interface.