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Although sleep disturbances are common co-morbidities of metabolic diseases, the underlying processes linking both are not yet fully defined. Changes in the duration of sleep are paralleled by changes in the levels of insulin-like growth factor-I (IGF-I), an anabolic hormone that shows a circadian pattern in the circulation and activity-dependent entrance in the brain. However, the specific role, if any, of IGF-I in this universal homeostatic process remains poorly understood. We now report that the activity of orexin neurons, a discrete cell population in the lateral hypothalamus that is involved in the circadian sleep/wake cycle and arousal, is modulated by IGF-I. Furthermore, mice with blunted IGF-I receptor activity in orexin neurons have lower levels of orexin in the hypothalamus, show altered electro-corticographic patterns with predominant slow wave activity, and reduced onset-sleep latency. Collectively, these results extend the role in the brain of this pleiotropic growth factor to shaping sleep architecture through the regulation of orexin neurons. We speculate that poor sleep quality associated to diverse conditions may be related to disturbed brain IGF-I input to orexin neurons.Whole blood is often collected for large-scale immune monitoring studies to track changes in cell frequencies and responses using flow (FC) or mass cytometry (MC). In order to preserve sample composition and phenotype, blood samples should be analyzed within 24 h after bleeding, restricting the recruitment, analysis protocols, as well as biobanking. Herein, we have evaluated two whole blood preservation protocols that allow rapid sample processing and long-term stability. Two fixation buffers were used, Phosphoflow Fix and Lyse (BD) and Proteomic Stabilizer (PROT) to fix and freeze whole blood samples for up to 6 months. After analysis by an 8-plex panel by FC and a 26-plex panel by MC, manual gating of circulating leukocyte populations and cytokines was performed. Additionally, we tested the stability of a single sample over a 13-months period using 45 consecutive aliquots and a 34-plex panel by MC. We observed high correlation and low bias toward any cell population when comparing fresh and 6 months frozen blood with FC and MC. This correlation was confirmed by hierarchical clustering. Low coefficients of variation (CV) across studied time points indicate good sample preservation for up to 6 months. Cytokine detection stability was confirmed by low CVs, with some differences between fresh and fixed conditions. Thirteen months regular follow-up of PROT samples showed remarkable sample stability. Whole blood can be preserved for phenotyping and cytokine-response studies provided the careful selection of a compatible antibody panel. However, possible changes in cell morphology, differences in antibody affinity, and changes in cytokine-positive cell frequencies when compared to fresh blood should be considered. Our setting constitutes a valuable tool for multicentric and retrospective studies. © 2020 International Society for Advancement of Cytometry. Ablation of septal substrate-associated ventricular tachycardia (VT) in patients with nonischemic cardiomyopathy (NICM) is challenging. We sought to standardize the characterization of septal substrates on late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) and to examine the association of that substrate with VT exit and isthmus sites on invasive mapping. LGE-CMR was performed before electroanatomic mappingand ablation for VT in 20 NICM patients. LGE extent and distribution were quantified using myocardial signal-intensity Z scores (SI-Z). The SI-Z thresholds correlating to previously validated voltage thresholds, for abnormal tissue and dense scar were defined. Bipolar and unipolar (electrogram) voltage amplitude measurements from the LV and RV were negatively associated with SI-Z from LGE-CMR imaging (p < .05). SI-Z thresholds for appropriate CMR identification of septal substrates were determined to be greater than-.15 for border zone and greater than .03 for a dense scar. Among all patients, 34 critical VT sites were identified with SI-Z distribution in the range of -.97 to .06. Thirty (88.2%) critical sites were located in the dense LGE, 1 (2.9%) in the border zone, and 3 (8.9%) in healthy tissue but within 7 mm of LGE. Of note, critical VT sites were all located at the basal septum close to valves (distance to aortic valve 17.5 ± 31.2 mm, mitral valve 21.2 ± 8.7 mm) in nonsarcoidosis cases. Critical sites of septal VT in NICM patients are predominantly in the CMR defined dense scar when using standardized signal-intensity thresholds. Critical sites of septal VT in NICM patients are predominantly in the CMR defined dense scar when using standardized signal-intensity thresholds.We presented a case of severe aortic regurgitation and moderate mitral regurgitation s/p aortic valve replacement and mitral valve repair. Deterioration of tachyarrhythmia attacks was noted. In EP study, left lateral accessory pathway with orthodromic atrioventricular reentrant tachycardia was identified. We successfully ablated the accessory pathway by trans-septal approach. Even though trans-septal approach currently is a daily routine of invasive interventional electrophysiologists, in this case, we want to emphasize and illustrate the distance between true mitral annulus and coronary sinus. https://www.selleckchem.com/products/pyrotinib.html Unrecognizing this concept could result in efficacy and safety of catheter-based therapy. The rapid spread of the pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/)(COVID-19) virus resulted in governments around the world instigating a range of measures, including mandating the wearing of face coverings on public transport/in retail outlets. We developed a sequential assessment of the risk reduction provided by face coverings using a step-by-step approach. The UK Office of National Statistics (ONS) Population Survey data were utilised to determine the baseline total number of community-derived infections. These were linked to reported hospital admissions/hospital deaths to create case admission risk ratio and admission-related fatality rate. We evaluated published evidence to establish an infection risk reduction for face coverings. We calculated an Infection Risk Score (IRS) for a number of common activities and related it to the effectiveness of reducing infection and its consequences, with a face covering, and evaluated their effect when applied to different infection rates over 3months from July 24, 2020, when face coverings were made compulsory in England on public transport/retail outlets.
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