Personal Financial Wellness Curricula for Medical Trainees: A Systematic Review.

PURPOSE: Education debt, poor financial literacy, and a late start to retirement savings can cause financial stress among physicians. This systematic review identifies methods for curriculum development, methods for curriculum delivery, and outcome measures to evaluate the effectiveness of personal financial wellness curricula for medical students, residents, and fellows. METHOD: The authors searched the Embase, MEDLINE (via EBSCO), Scopus, Education Resources Information Center (via EBSCO), and Cochrane Library databases and MedEdPORTAL (via PubMed) on July 28, 2022. Studies must have reported the outcome of at least 1 postcourse assessment to be included. RESULTS: Of the 1,996 unique citations identified, 13 studies met the inclusion criteria. Three curricula (23.1%) were designed for medical students, 8 (61.5%) for residents, 1 (7.7%) for internal medicine fellows, and 1 (7.7%) for obstetrics-gynecology residents and fellows. The most frequently discussed personal finance topics included student loans, investment options, disability insurance, life insurance, retirement savings, budgeting, debt management, and general personal finance. A median (interquartile range) of 3.5 (1.4-7.0) hours was spent on personal finance topics. Eleven curricula (85.6%) relied on physicians to deliver the content. Four studies (30.8%) reported precourse and postcourse financial literacy evaluations, each showing improved financial literacy after the course. Four studies (30.8%) assessed actual or planned financial behavior changes, each credited with encouraging or assisting with financial behavioral changes. One study (7.7%) assessed participants' well-being using the Expanded Well-Being Index, which showed an improvement after the course. CONCLUSIONS: Given the impact educational debt and other financial stressors can have on the wellness of medical trainees, institutions should consider investments in teaching financial literacy. Future studies should report more concrete outcome measures, including financial behavior change and validated measures of wellness.

Prostate tumor cell exosomes containing hyaluronidase Hyal1 stimulate prostate stromal cell motility by engagement of FAK-mediated integrin signaling.

The hyaluronidase Hyal1 is clinically and functionally implicated in prostate cancer progression and metastasis. Elevated Hyal1 accelerates vesicular trafficking in prostate tumor cells, thereby enhancing their metastatic potential in an autocrine manner through increased motility and proliferation. In this report, we found Hyal1 protein is a component of exosomes produced by prostate tumor cell lines overexpressing Hyal1. We investigated the role of exosomally shed Hyal1 in modulating tumor cell autonomous functions and in modifying the behavior of prostate stromal cells. Catalytic activity of Hyal1 was necessary for enrichment of Hyal1 in the exosome fraction, which was associated with increased presence of LC3BII, an autophagic marker, in the exosomes. Hyal1-positive exosome contents were internalized from the culture medium by WPMY-1 prostate stromal fibroblasts. Treatment of prostate stromal cells with tumor exosomes did not affect proliferation, but robustly stimulated their migration in a manner dependent on Hyal1 catalytic activity. Increased motility of exosome-treated stromal cells was accompanied by enhanced adhesion to a type IV collagen matrix, as well as increased FAK phosphorylation and integrin engagement through dynamic membrane residence of ß1 integrins. The presence of Hyal1 in tumor-derived exosomes and its ability to impact the behavior of stromal cells suggests cell-cell communication via exosomes is a novel mechanism by which elevated Hyal1 promotes prostate cancer progression.

3,5-Disubstituted-indole-7-carboxamides as IKKß Inhibitors: Optimization of Oral Activity via the C3 Substituent.

IκB kinase ß (IKKß or IKK2) is a key regulator of nuclear factor kappa B (NF-κB) and has received attention as a therapeutic target. Herein we report on the optimization of a series of 3,5-disubstituted-indole-7-carboxamides for oral activity. In doing so, we focused attention on potency, ligand efficiency (LE), and physicochemical properties and have identified compounds 24 and (R)-28 as having robust in vivo activity.

4-Phenyl-7-azaindoles as potent, selective and bioavailable IKK2 inhibitors demonstrating good in vivo efficacy.

The lead optimization of a series of potent azaindole IKK2 inhibitors is described. Optimization of the human whole blood activity and selectivity over IKK1 in parallel led to the discovery of 16, a potent and selective IKK2 inhibitor showing good efficacy in a rat model of neutrophil activation.

Identification of [4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)-2-pyrimidinyl] amines and ethers as potent and selective cyclooxygenase-2 inhibitors.

A novel series of [4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)-2-pyrimidine-based cyclooxygenase-2 (COX-2) inhibitors, which have a different arrangement of substituents compared to the more common 1,2-diarylheterocycle based molecules, have been discovered. For example, 2-(butyloxy)-4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)pyrimidine (47), a member of the 2-pyrimidinyl ether series, has been shown to be a potent and selective inhibitor with a favourable pharmacokinetic profile, high brain penetration and good efficacy in rat models of hypersensitivity.

4-Phenyl-7-azaindoles as potent and selective IKK2 inhibitors.

The synthesis and SAR of a novel series of IKK2 inhibitors are described. Modification around the hinge binding region of the 7-azaindole led to a series of potent and selective inhibitors with good cellular activity.

Antithrombotic therapy for stroke in young adults.

Stroke in young adults is a markedly heterogeneous disease, and remains an understudied phenomenon. While advances are being made in our understanding of the pathophysiology of its underlying conditions, treatment concerns are controversial, and clinical trials are sorely lacking. This review presents an overview of some of the relevant management issues in hypercoagulable states, migraine, patent foramen ovale, vascular dissection and venous sinus thrombosis.