Natural products are a major source for cancer drug development. NK cells are a critical component of innate immunity with the capacity to destroy cancer cells, cancer initiating cells, and clear viral infections. However, few reports describe a natural product that selectively stimulates NK cell IFN-γ production and unravel a mechanism of action. In this study, through screening, we found that a natural product, phyllanthusmin C (PL-C), alone enhanced IFN-γ production by human NK cells. PL-C also synergized with IL-12, even at the low cytokine concentration of 0.1 mg/ml, and stimulated IFN-γ production in both human CD56bright and CD56dim NK cell subsets. Mechanistically, TLR1 and/or TLR6 mediated PL-C’s activation of the NF-κB p65 subunit that in turn bound to the proximal promoter of IFNG and subsequently resulted in increased IFN-γ production in NK cells. However, IL-12/IL-15 receptors and their related STAT signaling pathways were not significantly modulated by PL-C. PL-C induced little or no T cell IFN-γ production or NK cell cytotoxicity. Collectively, we identify a natural product with the capacity to selectively activate human NK cell IFN-γ. Given the role of IFN-γ in immune surveillance, additional studies to understand the role of this natural product in prevention of cancer or infection in select populations are warranted.

We present the novel use of a deep learning–derived technology trained on the skilled hand movements of cardiac sonographers that guides novice users to acquire high-quality bedside cardiac ultrasound images. We illustrate its use at the point of care through a series of patient encounters in the COVID-19 intensive care unit. ( Level of Difficulty: Beginner. )

Acute heart failure (HF) is a global pandemic with more than one million admissions to hospital annually in the US and millions more worldwide. Post-discharge mortality and readmission rates remain unchanged and unacceptably high. Although recent drug development programmes have failed to deliver novel therapies capable of reducing cardiovascular morbidity and mortality in patients hospitalized for worsening chronic HF, hospitalized HF registries and clinical trial databases have generated a wealth of information improving our collective understanding of the HF syndrome. This review will summarize key insights from clinical trials in acute HF and hospitalized HF registries over the last several decades, focusing on improving the management of patients with HF and reduced ejection fraction.

Plasma renin activity is reduced early and durably by aliskiren, but this did not translate into improved clinical outcomes in ASTRONAUT. Baseline PRA or short-term reduction in PRA do not identify a subgroup who may preferentially benefit from direct renin inhibition. Clinical Trial Registration ClinicalTrials.gov Unique Identifier: NCT00894387.

Heart failure is a complex disease process, the manifestation of various cardiac and noncardiac abnormalities. General treatment approaches for heart failure have remained the same over the past decades despite the advent of novel therapies and monitoring modalities. In the same vein, the readmission rates for heart failure patients remain high and portend a poor prognosis for morbidity and mortality. In this context, development and implementation of improved algorithms for assessing and treating HF patients during hospitalization remains an unmet need. We propose an expanded algorithm for both monitoring and treating patients admitted for acute decompensated heart failure with the goal to improve post-discharge outcomes and decrease rates of rehospitalizations.

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Background Elite athletes show structural cardiac changes as an adaptation to exercise. Studies examining strain in athletes have largely analyzed images at rest only. There is little data available regarding the change in strain with exercise. Our objectives were: to investigate the feasibility of strain analysis in athletes at peak exercise, to determine the normal range of left ventricular (LV) global longitudinal strain (GLS) within this population postexercise, to describe how LV GLS changes with exercise, and to determine whether any clinical characteristics correlate with the change in GLS that occurs with exercise. Methods We conducted a cross‐sectional study on elite athletes who participated in the 2016–2018 National Basketball Association Draft Combines. Echocardiograms were obtained at rest and after completing a treadmill stress test to maximal exertion or completion of Bruce protocol. Primary outcomes included GLS obtained at rest and peak exercise. Secondary outcome was the change in GLS between rest and exercise. Univariate relationships between various clinical characteristics and our secondary outcome were analyzed. Results Our final cohort (n = 111) was all male and 92/111 (82.9%) were African American. Mean GLS magnitude increased in response to exercise (−17.6 ± 1.8 vs −19.2 ± 2.6, P < .0001). Lower resting heart rates (r = .22, P = .02) and lower heart rates at peak exercise (r = .21, P = .03) correlated with the increase in LV GLS from exercise. Conclusions Strain imaging is technically feasible to obtain among elite basketball athletes at peak exercise. Normative strain response to exercise from this study may help identify abnormal responses to exercise in athletes.

IntroductionAtrial dilatation is common but of unclear physiologic significance in high‐performance athletes. Myocardial deformation analysis utilizing speckle‐tracking echocardiography has emerged as a promising tool to evaluate atrial function. In a cohort of elite basketball players attending the National Basketball Association (NBA) Draft Combine, we investigate changes in left atrial (LA) size as well as function as measured by strain.Methods and ResultsFrom 2013 to 2018, all male athletes who attended the NBA Draft Combine in Chicago, IL, received a cardiac evaluation including a comprehensive transthoracic echocardiogram. Using the P‐wave as the reference point, speckle‐tracking was utilized to measure LA booster, conduit, and reservoir strain over one cardiac cycle. Left atrial volume index (LAVI) of ≥34 mL/m2 was considered enlarged. 307 athletes received cardiac evaluation including a transthoracic echocardiogram, with 272 studies amenable for atrial strain analysis. Mean age was 21.0 years. Mean LAVI was 34.5 mL/m2 and LAVI was enlarged in 131 (48.2%) athletes. Comparing LA strain in those with enlarged vs normal sized atria, reservoir strain was significantly reduced (32.1% [SD 6.0%] vs 35.2% [SD 8.2%], P < .001), as was conduit strain (22.9% [SD 5.2%] vs 25.7% [SD 7.4%], P < .001), with no difference seen in booster strain (9.2% [SD 2.1%] vs 9.4% [SD 2.7%], P = .45).ConclusionIn this group of elite basketball players, LA enlargement was common and associated with reduced LA reservoir and conduit strain, with no difference in LA booster strain.