Literature Collection

Professionalism in any field requires keeping pace with change, and nowhere is it more true than medicine. Knowledge flow has changed dramatically since today's accreditation standards were developed, and change continues more rapidly than ever. It's time for a fresh look at how best to achieve care in this altered environment, where valid knowledge may come from the patient as well as from clinician resources: a sociological change driven by technological change. The power structure of the clinical relationship is inevitably altered as constraints on patient knowledge are loosened by the internet, apps, and devices, undermining a paradigm of patients as uninformed recipients of care based on a one-way flow of wisdom from providers. Case after case is presented showing that patients today have generated undeniable value, violating the expectations and assumed best practices of the old model. To understand this sociological (yet scientific) change, this article reviews the role of paradigms in the history of sciences as described in Thomas Kuhn's landmark book The Structure of Scientific Revolutions and describes how these anomalous patient stories force the conclusion that the traditional paradigm of patients is no longer supportable and a new paradigm is needed. This in turn means our standards of professionalism and appropriate care must be updated, lest we fail to achieve best possible care in our increasingly overburdened system. Our new standard must be to teach clinicians to recognize, welcome, and work with empowered "e-patients" in the new model of participatory medicine.

BACKGROUND: Suicide rates in older men are higher than in the general population, yet their utilization of mental health services is lower. AIMS: This study aimed to describe: (a) what primary care providers (PCPs) can do to prevent late-life suicide, and (b) older men's attitudes toward discussing suicide with a PCP. METHOD: Thematic analysis of interviews focused on depression and suicide with 77 depressed, low-socioeconomic status, older men of Mexican origin, or US-born non-Hispanic whites recruited from primary care. RESULTS: Several themes inhibiting suicide emerged: it is a problematic solution, due to religious prohibition, conflicts with self-image, the impact on others; and, lack of means/capacity. Three approaches to preventing suicide emerged: talking with them about depression, talking about the impact of their suicide on others, and encouraging them to be active. The vast majority, 98%, were open to such conversations. An unexpected theme spontaneously arose: "What prevents men from acting on suicidal thoughts?" CONCLUSION: Suicide is rarely discussed in primary care encounters in the context of depression treatment. Our study suggests that older men are likely to be open to discussing suicide with their PCP. We have identified several pragmatic approaches to assist clinicians in reducing older men's distress and preventing suicide.

To develop novel analgesics with no side effects or less side effects than traditional opioids is highly demanded to treat opioid receptor mediated pain and addiction issues. Recently, kappa-opioid receptor (KOR) has been established as an attractive target, although its selective agonists could bear heterogeneous pharmacological activities. In this study, we designed and synthesized two new series of nepenthone derivatives by inserting a spacer (carbonyl) between 6alpha,14alpha-endo-ethenylthebaine and the 7alpha-phenyl substitution of the skeleton and by substituting the 17-N-methyl group with a cyclopropylmethyl group. We performed in vitro tests (binding and functional assays) and molecular docking operations on our newly designed compounds. The results of wet-experimental measures and modeled binding structures demonstrate that these new compounds are selective KOR agonists with nanomolar level affinities. Compound 4 from these new derivatives showed the highest affinity (Ki = 0.4 +/- 0.1 nM) and the highest selectivity (mu/kappa = 339, delta/kappa = 2034) toward KOR. The in vivo tests revealed that compound 4 is able to induce stronger (ED50 = 2.1 mg/kg) and much longer antinociceptive effect than that of the typical KOR agonist U50488H (ED50 = 4.4 mg/kg). Therefore, compound 4 can be used as a perfect lead compound for future design of potent analgesics acting through KOR.