Monocytes and macrophages play pivotal roles in inflammation and homeostasis. Recent studies suggest that dynamic programing of macrophages and monocytes may give rise to distinct “memory” states. Lipopolysaccharide (LPS), a classical pattern recognition molecule, dynamically programs innate immune responses. Emerging studies have revealed complex dynamics of cellular responses to LPS, with high doses causing acute, resolving inflammation, while lower doses are associated with low-grade and chronic non-resolving inflammation. These phenomena hint at dynamic complexities of intra-cellular signaling circuits downstream of the Toll-like receptor 4 (TLR4). In this review, we examine pathological effects of varying LPS doses with respect to the dynamics of innate immune responses and key molecular regulatory circuits responsible for these effects.
Background: Super-low-dose endotoxin causes mild but significant pro-inflammatory skewing. Results: Inhibition of GSK3 or activation of CREB ablates preferential induction of pro-inflammatory genes by super-low-dose LPS. Conclusion: GSK3 is necessary for pro-inflammatory gene induction in response to super-low-dose LPS, acting by activating FoxO1 and suppressing CREB. Significance: Persistent, non-resolving inflammation is a characteristic of many chronic diseases, and this study points toward potential therapeutic targets.
To learn how to improve telemedicine for adults >65, we asked primary care clinicians (“PCPs”) affiliated with one large Boston-area health system their views on using telemedicine (which included phone-only or video visits) with adults >65 during the COVID-19 pandemic. In open-ended questions, we asked PCPs to describe any challenges or useful experiences with telemedicine and suggestions for improving telemedicine as part of a larger web-based survey conducted between September 2020 and February 2021. Overall, 163/383 (42%) PCPs responded to the survey. Of these, 114 (70%) completed at least one open-ended question, 85% were non-Hispanic white, 59% were female, 75% were community-based, and 75% were in practice >20 years. We identified three major themes in participants’ comments including the need to optimize telemedicine; integrate telemedicine within primary care; and that PCPs had disparate attitudes towards telemedicine for older adults. To optimize telemedicine, PCPs recommended more effective digital platforms, increased utilization of home medical equipment (e.g., blood pressure cuffs), and better coordination with caregivers. For integration, PCPs recommended targeting telemedicine for certain types of visits (e.g., chronic disease management), enabling video access, and reducing administrative burdens on PCPs. As for PCP attitudes, some felt telemedicine enhanced the doctor-patient relationship, improved the patient experience, and improved show rates. Others felt that telemedicine visits were incomplete without a physical exam, were less rewarding, and could be frustrating. Overall, PCPs saw a role for telemedicine in older adults’ care but felt that more support is needed for these visits than currently offered.
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