Due to the location and high dose required for disease control, pediatric chordomas are theoretically well-suited for treatment with proton therapy, but their low incidence limits the clinical outcome data available in the literature. We sought to report the efficacy and toxicity of proton therapy among a single-institution cohort.
 
  Between 2008 and 2019, 29 patients with a median age of 14.8 years (range, 3.8-21.8) received passive-scattered proton therapy for nonmetastatic chordoma. No patient received prior irradiation. Twenty-four tumors arose in the clivus/cervical spine region and 5 in the lumbosacral spine. Twenty-six tumors demonstrated classic well-differentiated histology and 3 were dedifferentiated or not otherwise specified. Approximately half of the tumors underwent specialized testing 14 were brachyury-positive and 10 retained INI-1. Three patients had locally recurrent tumors after surgery alone (n = 2) or surgery + chemotherapy (n = 1), and 17 patients had gross disease at the time of radiamplete resection may be unnecessary for local control, and destabilizing operations requiring instrumentation may result in additional complications after therapy.
 In pediatric patients with chordoma, proton therapy is associated with a low risk of serious toxicity and high efficacy, particularly in well-differentiated tumors. Complete resection may be unnecessary for local control, and destabilizing operations requiring instrumentation may result in additional complications after therapy.Emotion has a strong modulatory effect on pain perception and spinal nociception. Pleasure inhibits pain and nociception, whereas displeasure facilitates pain and nociception. Dysregulation of this system has been implicated in development and maintenance of chronic pain. The current study sought to examine whether emotional modulation of pain could be altered through the use of transcranial direct current stimulation (tDCS) to enhance (via anodal stimulation) or depress (via cathodal stimulation) cortical excitability in the dorsolateral prefrontal cortex. Thirty-two participants (15 female, 17 male) received anodal, cathodal, and sham tDCS on three separate occasions, followed immediately by testing to examine the impact of pleasant and unpleasant images on pain and nociceptive flexion reflex (NFR) responses to electrocutaneous stimulation. Results indicated that tDCS modulated the effect of image content on NFR, F(2, 2175.06) = 3.20, P= .04, with the expected linear slope following anodal stimulation (ie, pleasant less then neutral less then unpleasant) but not cathodal stimulation. These findings provide novel evidence that the dorsolateral prefrontal cortex is critical to emotional modulation of spinal nociception. Moreover, the results suggest a physiological basis for a previously identified phenotype associated with risk for chronic pain and thus a potentially new target for chronic pain prevention efforts. PERSPECTIVE This study demonstrated that reduction of dorsolateral prefrontal cortical excitability by transcranial direct current stimulation attenuates the impact of emotional image viewing on nociceptive reflex activity during painful electrocutaneous stimulation. This result confirms there is cortical involvement in emotional modulation of spinal nociception and opens avenues for future clinical research.Brown adipose tissue (BAT) activation or beige adipocytes in white adipocytes (WAT) (browning) is a novel strategy against obesity. Corylin, a flavonoid compound extract from Psoralea corylifolia L., has been shown to exert anti-inflammatory, anticancer, and anti-atherosclerotic effects and ameliorate hyperlipidemia and insulin resistance. However, the therapeutic effect of corylin on obesity remains unknown. The objective of this study was to evaluate the effect of corylin on browning or obesity. Here, we report that corylin induced browning by elevating the expression levels of beige- or browning-specific marker genes, including cited1, hoxc9, pgc1α, prdm16, and ucp1, in 3T3-L1 adipocytes, WAT and BAT.  https://www.selleckchem.com/products/afuresertib-gsk2110183.html  Moreover, corylin also strikingly reduced body weight and fat accumulation and increased insulin sensitivity, mitochondrial biogenesis, and β-oxidation in HFD- and DIO-treated mice. The browning and lipolysis effects of corylin were abolished by sirtuin 1 (SIRT1) inhibitor (EX527) and β3-adrenergic receptor (β3-AR) antagonist (L-748,337) treatment. The possible molecular mechanism of corylin on the browning and lipolysis of adipocytes is through SIRT1- or β3-AR-dependent pathways. The study suggested that corylin exerts anti-obesity effects through the browning of white adipocytes, activating of BAT and promoting of lipid metabolism. Therefore, corylin may be a helpful therapeutic candidate for treating obesity.
  Intermittent high-mechanical index (MI) impulses from a transthoracic ultrasound transducer are recommended for regional wall motion analysis and assessment of myocardial perfusion following intravenous administration of ultrasound enhancing agents (UEAs). High-MI impulses (>1.0) applied in this setting have also been shown to increase microvascular blood flow through a purinergic signaling pathway, but their effects on left ventricular (LV) myocardial function are unknown. Therefore, the aim of this study was to investigate the effect of transthoracic intermittent high-MI impulses during intravenous UEA infusion in patients with normal and abnormal resting systolic function.
 
  Fifty patients referred for echocardiography to evaluate LV systolic function during continuous infusion of UEAs (Definity 3% infusion) were prospectively assigned to low-MI (<0.2) imaging alone (group 1) or low-MI (<0.2) imaging with intermittent high-MI impulses (five frames, 1.8MHz, MI=1.0-1.2) applied at least two times V dysfunction.
 High-MI impulses during infusion of a commercially available contrast agent can improve LV systolic function and may have therapeutic effect in patients with LV dysfunction.
  Aortic regurgitation (AR) is a common valvular lesion associated with increased mortality once the left ventricle enlarges significantly or develops systolic dysfunction (ejection fraction<50%). Valve guidelines recommend aortic valve repair or replacement (AVR) for left ventricular (LV) linear end-systolic dimension≥50mm or end-diastolic dimension≥65mm. However, chamber quantification guidelines recommend using LV volume for LV size determination because linear measurements may not accurately reflect LV remodeling. The aim of this study was to evaluate the correlation of LV volumes with linear dimensions, interobserver variability in the estimation of volumes, and the association of volumes with outcomes in patients with AR.
 
  A total of 1,100 consecutive patients with chronic moderate to severe and severe AR on echocardiography between 2004 and 2019 were retrospectively analyzed. The modified Simpson disk summation method was used for LV volume estimation. The primary outcome was all-cause mortality; the secondary outcome was mortality censored at AVR.