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Abstract Background The ‘OPTIMAL’ (Optimizing Performance Through Intrinsic Motivation for Learning) theory of motor learning suggests that autonomy, external focus of attention, and perceived competence can improve learning of simple motor tasks. The authors hypothesized that enhanced (vs. routine) autonomy and external (vs. internal) focus of attention would improve first-try performance of two medical motor tasks.Methods The authors conducted a randomized two-by-two factorial design study with high school students as participants. Task instructions promoted either enhanced or routine autonomy, and either external or internal focus of attention. These conditions were replicated in a crossover design for two common medical tasks (chest compressions on a manikin and a Fundamentals of Laparoscopic Surgery peg transfer task). Primary outcomes were objective measures of task performance (chest compression deviation from target depth; peg transfer time with penalties for errors). Secondary outcomes included subjective perceptions of confidence, autonomy, and workload.Results 133 high school students participated in this study. The primary outcomes concerning enhanced vs. routine autonomy demonstrated no statistically significant difference in either task (chest compression depth deviation: difference − 0.7 mm [score range 0 to 37.5 mm]; 95% confidence interval (CI95) -3.85, 2.41; p = .65; peg transfer penalized time: rate ratio 1.03; CI95 0.91, 1.31; p = .79). The authors likewise found no statistically significant difference for external vs. internal focus of attention (depth deviation: difference 1.1 mm; CI95 -2.04, 4.17; p = .50; penalized time: rate ratio 0.89; CI95 0.75, 1.13; p = .33). The authors found no statistically significant differences for either comparison in confidence, autonomy and workload (p > .09; differences ranged from − 0.83 to 0.79 [scale range 0 to 10]).Conclusions First-try performance of chest compressions and peg transfer by novice learners is not significantly affected by enhanced (vs. routine) autonomy or external (vs. internal) focus of attention.

Acute systemic induced inflammation negatively affects arterial function in young healthy adults. An acute bout of aerobic exercise reduces arterial stiffness and improves endothelial function. Therefore, we evaluated endothelial function and wave reflection in older adults in response to acute systemic inflammation and the effect of moderate intensity endurance exercise immediately prior to induced inflammation. 59 healthy volunteers (range 55 – 75 years) were randomly allocated to an exercise or control group. Arterial function and inflammatory markers were measured at baseline, 24 h and 48 h after influenza vaccine and sham injections. CRP increased approximately 1.5 times, 24 and 48 h after vaccination while IL‐6 increased 24 hours after vaccination compared to the sham injection. Unexpectedly, arterial function was unaltered (Table). Inflammation and endothelial function were dissociated following vaccine‐induced acute systemic inflammation in older adults. Acute exercise prior to vaccination had no effect of inflammation or vascular function. Support: AHA #10PRE3500083 (SMR).

Introduction Heart rate variability (HRV), blood pressure variability (BPV) and baroreflex sensitivity (BRS), measures of autonomic nervous system function, are associated with cardiovascular (CV) outcome. African Americans (AA) have an increased prevalence of CV disorders in comparison to Caucasians (C). Purpose To determine race specific responses in BPV, BRS and HRV before and after maximal exercise. Methods 37 AA and 37 C (24 years) underwent maximal exercise on a cycle ergometer. BPV, BRS and HRV measurements were assessed using finger plethysmography before and after exercise. Data were log transformed and pre‐and post‐max test values were compared by race. Results Acute exercise significantly decreased BRS, LF‐HRV and HF‐HRV and significantly increased LF/HF‐HRV in both AA and C. With exercise, C significantly decreased measures of BRS and HRV more compared to AA; BRS‐SAPRRI transfer mean (C: 2.65±.54 to 1.09±.81 versus AA: 2.70±.40 to 1.70±.92), BRS‐down down (C: 3.21±.55 to 1.74±.49 versus AA: 3.28±1.0 to 2.2±.71), HRV‐LF (C: 6.39±.86 to 3.68±1.42 versus AA: 6.37±1.24 to 5.18±2.14) and HRV‐HF (C: 7.38±1.23 to 3.53±1.73 versus AA: 7.51±1.09 to 5.38±2.16). Conclusion C exhibited increased vagal withdrawal and greater reductions in BRS compared to AA in response to acute exercise. The impact of these racial differences in autonomic control on CV risk needs further investigation.

Hospitalized patients with COVID-19 show increased serum concentrations of neurofilament light chain that correlate with worse clinical outcomes.

PURPOSE:This randomized, double-blind study sought to understand whether cancer clinical trial consent form verbosity detracts from patients' decision making on trial enrollment.METHODS:This trial tested mock consent forms of 2,000, 4,000, and 6,000 words. The first two comprised the two experimental arms and the third the control arm. Phase II was conducted to identify the promising arm, which, in phase III, was compared with the control arm. Each consent form described the same trial. Eligible adult patients reported a cancer history and English literacy. The primary end point used a patient-reported Likert scale to assess the relationship between information in the consent form and trial decision making.RESULTS:In phase II, 93 patients were accrued and prompted the selection of the 2,000-word consent form for phase III. In phase III, 182 patients were recruited, resulting in 240 total evaluable patients to compare the 2,000-word versus the 6,000-word arm (control). For the primary end point, 103 (84%) and 107 (91%) patients in the 2,000- and 6,000-word arms, respectively, strongly agreed or agreed with the following: “The information in this consent form helped me make a decision about whether or not to enroll in the trial” (two-sided, P = .14). Median time to read each consent form was 8 and 12 minutes, respectively (two-sided, P < .0001). Among those assigned these consent forms, 84% and 73%, respectively (two-sided, P = .04) signed or expressed a willingness to sign.CONCLUSION:This study's primary end point was not met. However, secondary outcomes suggest a need to further study the efficiency and efficacy of shorter consent forms for cancer clinical trial enrollment.

High salt diet (HS) impairment of endothelial nitric oxide (NO) signaling has been described in human and rodents. The mechanisms which mediate this dysfunction remain unknown. We and others have previously shown histone deacetylase 1 (HDAC1) decreases endothelial NO production. We therefore sought to investigate the mechanisms by which HS initiates endothelial dysfunction and if it is HDAC1‐dependent. We first investigated if HS induced endothelial dysfunction is acutely regulated by a circulating factor. Male Sprague Dawley rats were fed normal salt diet (NS; 0.49% NaCl) or 2 weeks of HS (4.0% NaCl). Afferent arteriole vasoconstrictor responses to the NOS inhibitor, L‐NAME, were monitored using the in vitro, blood perfused juxtamedullary nephron preparation. Arterioles from HS fed rats perfused with blood from HS fed rats demonstrated blunted constriction to L‐NAME (96 ± 2% of Con) compared to arterioles from NS fed rats perfused with blood from NS fed rats (76.2 ± 2% of Con; P=0.0017). Perfusing arterioles from NS fed rats with blood HS fed rats blunted constriction to L‐NAME (88 ± 1% of Con) compared to perfusing with blood from NS fed rats (P=0.0003), but not to the same extent as arterioles from HS fed rats perfused with blood from HS fed rats (P=0.0095). HS arterioles perfused with blood from NS fed rats had similar L‐NAME‐induced constriction (75 ± 2% of Con) compared to arterioles from NS fed rats perfused with blood from NS fed rats (P=0.9107). In short, the impaired constriction to L‐NAME is dependent up on the diet of the blood donor and not the diet of the arteriole donor suggesting HS impairs endothelial function through an acute‐acting circulating factor. This was not due to increased plasma arginase activity (NS: 7.96 ± 3.73 U/L vs HS: 5.42 ± 1.83 U/L P=0.5813), changes in plasma tetrahydrobiopterin (NS: 65.09 ± 11.57 pmol/ml vs HS: 53.54 ± 5.59 pmol/ml, P=0.311) or changes in plasma dihydrobiopterin (NS: 98.18 ± 7.84 pmol/ml vs HS: 87.45 ± 13.28 pmol/ml, P=0.530). We then investigated if HS increased endothelial HDAC1 activity. Renal endothelial cells were isolated from NS and HS fed rats and incubated in plasma from the same rat. HDAC1 activity was defined as the MS‐275 (HDAC1 specific inhibitor) inhibitable portion of total HDAC activity. We found HS significantly increased renal endothelial HDAC1 activity (NS: 0.38 ± 0.03 pmol/min vs HS:0.94 ± 0.19 pmol/min, P=0.01). Furthermore, in vitro HDAC1 inhibition with 300 nM MS‐275 restored the arteriolar vasoconstrictor responses in HS rats (79 ± 3% of Con) to values similar to NS fed rats (P=0.969) and to NS rats + MS‐275 (79 ± 1% of Con; P>0.998). When plasma from HS fed rats was combined with erythrocytes from NS fed rats and perfused through arterioles from NS fed rats, constriction to L‐NAME was blunted (85 ± 3% of Con; P=0.0129). Under these same conditions, HDAC1 inhibition restored constriction (75.7 ± 0.95 % of Con) similar to controls (P=0.979). We conclude that HS disruption of renal microvascular NO signaling is initiated by a circulating factor(s) that increases endothelial HDAC1 activity.

Background: There is great degree of interobserver variability in the visual angiographic assessment of left main coronary disease (LMCD). Fractional flow reserve and intravascular ultrasound are often used in this setting. The use of instantaneous wave-free ratio (iFR) for evaluation of LMCD has not been well studied. The aim of this study is to evaluate the use of iFR in the assessment of angiographically intermediate LMCD. Methods: This is an international multicenter retrospective observational study of patients who underwent both iFR and intravascular ultrasound evaluation for angiographically intermediate LMCD. An independent core laboratory performed blinded off-line analysis of all intravascular ultrasound data. A minimum lumen area of 6 mm 2 was used as the cutoff for significant disease. Results: One hundred twenty-five patients (mean age, 68.4±9.5 years, 84.8% male) were included in this analysis. Receiver operating curve analysis showed that an iFR of ≤0.89 identified minimum lumen area <6 mm 2 with an area under the curve of 0.77 (77% sensitivity, 66% specificity; P <0.0001). Among the 69 patients without ostial left anterior descending artery or left circumflex artery disease, receiver operating curve analysis showed that an iFR of ≤0.89 identified minimum lumen area <6 mm 2 with an area under the curve of 0.84 (70% sensitivity, 84% specificity; P <0.0001). The correlation was not significantly different when the body surface area was considered. Conclusions: In this study, in patients with intermediate LMCD, iFR of ≤0.89 correlates with intravascular ultrasound minimum lumen area <6 mm 2 regardless of body surface area. The current study supports the use of iFR for the evaluation of intermediate LMCD.