Publications by authors named "Jonathan M Philpott"

PERIOD (PER) and Casein Kinase 1δ regulate circadian rhythms through a phosphoswitch that controls PER stability and repressive activity in the molecular clock. CK1δ phosphorylation of the familial advanced sleep phase (FASP) serine cluster embedded within the Casein Kinase 1 binding domain (CK1BD) of mammalian PER1/2 inhibits its activity on phosphodegrons to stabilize PER and extend circadian period. Here, we show that the phosphorylated FASP region (pFASP) of PER2 directly interacts with and inhibits CK1δ.

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Background: Myocardial tissue can be ablated by the application nanosecond pulsed fields (nsPEFs). The applied electric fields irreversibly permeabilize cell membranes and thereby kill myocytes while leaving the extracellular matrix intact.

Methods: In domestic pigs (n = 10), hearts were exposed via sternotomy and either ablated in vivo ([Formula: see text] = 5) or in excised, Langendorff-perfused hearts ([Formula: see text] = 5).

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Genetically encoded biological clocks are found broadly throughout life on Earth, where they generate circadian (about a day) rhythms that synchronize physiology and behavior with the daily light/dark cycle. Although the genetic networks that give rise to circadian timing are now fairly well established, our understanding of how the proteins that constitute the molecular 'cogs' of this biological clock regulate the intrinsic timing, or period, of circadian rhythms has lagged behind. New studies probing the biochemical and structural basis of clock protein function are beginning to reveal how assemblies of dedicated clock proteins form and evolve through post-translational regulation to generate circadian rhythms.

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Left ventricular assist devices (LVADs) have become integral to the treatment of advanced heart failure. Surgical bleeding is a known complication of LVAD placement but is most associated with intraperitoneal pump locations. Here we describe a case of massive postoperative hemorrhage secondary to erosion of an intrapericardial LVAD into an intercostal artery with an associated rib fracture.

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Post-translational control of PERIOD stability by Casein Kinase 1δ and ε (CK1) plays a key regulatory role in metazoan circadian rhythms. Despite the deep evolutionary conservation of CK1 in eukaryotes, little is known about its regulation and the factors that influence substrate selectivity on functionally antagonistic sites in PERIOD that directly control circadian period. Here we describe a molecular switch involving a highly conserved anion binding site in CK1.

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Aims: Reliable defibrillation with reduced energy deposition has long been the focus of defibrillation research. We studied the efficacy of single shocks of 300 ns duration in defibrillating rabbit hearts as well as the tissue damage they may cause.

Methods And Results: New Zealand white rabbit hearts were Langendorff-perfused and two planar electrodes were placed on either side of the heart.

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Surgical ablation for atrial fibrillation (AF) can be performed without additional risk of operative mortality or major morbidity, and is recommended at the time of concomitant mitral operations to restore sinus rhythm. (Class I, Level A) Surgical ablation for AF can be performed without additional operative risk of mortality or major morbidity, and is recommended at the time of concomitant isolated aortic valve replacement, isolated coronary artery bypass graft surgery, and aortic valve replacement plus coronary artery bypass graft operations to restore sinus rhythm. (Class I, Level B nonrandomized) Surgical ablation for symptomatic AF in the absence of structural heart disease that is refractory to class I/III antiarrhythmic drugs or catheter-based therapy or both is reasonable as a primary stand-alone procedure, to restore sinus rhythm.

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Background: The Cox Maze-IV procedure (CMP-IV) has replaced the Cox Maze-III procedure as the most common approach for the surgical treatment of atrial fibrillation (AF). The Food and Drug Administration-regulated AtriCure Bipolar Radiofrequency Ablation of Permanent Atrial Fibrillation (ABLATE) trial sought to demonstrate the safety and efficacy of the CMP-IV performed with the Synergy ablation system (AtriCure, Inc, Cincinnati, OH).

Methods: Fifty-five patients (aged 70.

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Background: Hurthle cell carcinoma of the thyroid is a rare form of thyroid cancer. It may present as a low grade tumour or can present as a more aggressive metastatic carcinoma. Hurthle cell carcinoma has the highest incidence of metastasis among all differentiated thyroid cancers.

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Background: Replacement of the thoracic aorta is associated with a potential for interruption of the blood supply to the spinal cord leading to paralysis. Techniques have been proposed to ameliorate this risk, including reimplantation of the intercostal arteries. We present a technique to simplify this approach.

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Isolated iliac artery aneurysms are rare but dangerous aneurysms associated with a high incidence of rupture (between 14 and 70%). Rupture is frequently associated with an exceedingly high mortality primarily because of the elusive nature of the presenting symptoms and the resulting major delays in treatment. Accordingly these aneurysms are best managed aggressively.

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Posttraumatic urinomas are well-described complications associated with the nonoperative management of major blunt renal injuries. Urinoma drainage using a percutaneously placed catheter has been the traditional method used to alleviate symptoms and promote resolution without the need for open intervention. The authors describe 2 pediatric cases in which urinomas associated with grade IV renal lacerations were treated successfully utilizing internal ureteral stents.

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A case is presented in which significant single-vessel coronary artery disease and severe mitral valve regurgitation were successfully managed using combined minimally invasive direct coronary artery bypass and mitral valve repair. Although the management of coronary artery disease with simultaneous mitral valve disease has traditionally been approached using a median sternotomy, this combined minimally invasive approach led to a successful outcome and may serve as an alternative methodology for patients who are appropriate candidates.

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