Even with optimized medical care for the management of pain, many pediatric patients with sickle cell disease (SCD) report persistently high pain and have corresponding functional impairments. The Comfort Ability Program (CAP), a daylong pediatric pain management intervention, was adapted via a 4-phase knowledge translation process into a video-based intervention to specifically and flexibly address sickle cell pain (SCP). CAP for SCP introduces psychological and biobehavioral pain management techniques to adolescents with SCD and their parents or caregivers. A primary goal of our structured development process and feasibility testing was to ensure ease of access and delivery by addressing identified barriers to care that have historically limited widespread dissemination of evidence-based programs for patients with SCD. Method: The development of CAP for SCP was completed in 4 phases: (1) convening an expert panel to review the literature, discuss logistical and cultural barriers to care, and adapt the curriculum of a 1-day pain management workshop to a video-based format that could specifically meet the needs of a SCD population; (2) conducting a pilot testing of content with patients and parents followed by semistructured focus group discussion; (3) generating and producing the interactive video, audio materials, and corresponding workbook for intervention delivery; and (4) testing

The terms “prevention” and “risk reduction” are often used interchangeably in medicine. There is considerable debate, however, over the use of these terms in describing interventions that aim to preserve cognitive health and/or delay disease progression of Alzheimer's disease (AD) for patients seeking clinical care. Furthermore, it is important to distinguish between Alzheimer's disease prevention and Alzheimer's dementia prevention when using these terms. While prior studies have codified research-based criteria for the progressive stages of AD, there are no clear clinical consensus criteria to guide the use of these terms for physicians in practice. A clear understanding of the implications of each term will help guide clinical practice and clinical research. The authors explore the semantics and appropriate use of the terms “prevention” and “risk reduction” as they relate to AD in clinical practice.

We demonstrate for the first time that elevated concentrations of TMAO acutely augment myocardial contractile force ex vivo in both murine and human cardiac tissue. To gain mechanistic insight into the processes that led to this potentiation in cardiac contraction, we used two-photon microscopy to evaluate intracellular calcium in ex vivo whole hearts loaded with the calcium indicator dye Fluo-4. Acute treatment with TMAO resulted in increased Fluo-4 fluorescence, indicating that augmented cytosolic calcium plays a role in the effects of TMAO on force production. Lastly, TMAO did not show an effect on aortic smooth muscle contraction or relaxation properties. Our results demonstrate novel, acute, and direct actions of TMAO on cardiac function and help lay the groundwork for future translational studies investigating the complex multiorgan interplay involved in cardiovascular pathogenesis during CKD.

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BackgroundWhile it is understood that patients with chronic kidney disease (CKD) have an increased propensity for developing cardiovascular disease, the exact mechanisms remain unclear. Growing evidence suggests that the gut microbiome and its byproducts, such as TMAO, may be important contributors to this pathologic process. This uremic metabolite is cleared through renal excretion, which is compromised in CKD patients. Therefore, CKD patients often possess elevated plasma levels of this substance. In a previous study, we found that TMAO at pathological concentrations directly increases cardiac contractility in isolated, paced hearts. In this study, we sought to determine if TMAO also has chronotropic effects on isolated, spontaneously beating mouse hearts.MethodsWhole mouse hearts were extracted from anesthetized CD1 adult mice and subsequently connected to a force transducer and bubbled with oxygen inside an organ bath. The atria and sinoatrial node were kept intact to allow for spontaneous beating without artificial pacing. Changes in heart rate (in beats per minute) were measured after treatment with TMAO (3,000 μM) or vehicle (Ringer's solution). Additionally, calcium imaging was performed on cultured spontaneously beating embryonic rat cardiomyocytes. Intracellular Ca2+ responses in rat primary cardiomyocytes were measured with the fluorescent Ca2+ indicator Fura‐2 AM in response to vehicle and TMAO (3,000 uM).ResultsAverage beating frequency (in beats per minutes) of isolated hearts increased by 27% following treatment with 3,000 μM TMAO (P < 0.05, n =3) while there was no change with vehicle. Regarding isolated myocytes, TMAO was found to have a direct chronotropic effect as it increased beating frequency (as measured by calcium waves) by 13% compared to vehicle treatment (P < 0.05, n =4–5).ConclusionsIn addition to our previously described inotropic effects in the mouse heart, pathologic concentrations of TMAO also have a direct and positive chronotropic effect. The direct effects we have observed on the heart may increase cardiac output in early stages of CKD. However, cardiac remodeling as a result of increased beating frequency and contractility may have pathologic consequences in those with chronic disease. Further research is needed in order to elucidate the effect that TMAO has on cardiovascular function and pathology during CKD.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.