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Deals with the measurement of the mobilities of Li[sup+] ions in gaseous HCl, HBr and HI as a function of the energy parameter E/N at room temperature. Calculated mobilities of Li[sup+] ions in HCl, HBr and HI.

An easy method to prepare alkali ion emitters has been realized by using the ion-exchange technique. The thermionic emission characteristics of zeolite A alkali ion sources have been studied. Experimental results indicate that ion transport process within zeolite plays an important role in the emission mechanism. [ABSTRACT FROM AUTHOR]

Background: Despite improvements in outcomes of ST elevation myocardial infarction (STEMI), ventricular septal rupture (VSR) remains a known complication, carrying high mortality. The contemporary incidence, mortality, and management of post-STEMI VSR remains unclear., Methods: The National Inpatient Sample database (2009-2020) was used to study trends in admissions and outcomes of post-STEMI VSR over time. Survey estimation commands were used to determine weighted national estimates., Results: There were 2 315 186 ± 22 888 visits for STEMI with 0.194 ± 0.01% experiencing VSR during 2009-2020 in the USA. Patients with VSR were more often older, white, female, and presented with an anterior STEMI; there was no difference in the rates of fibrinolysis. In-hospital mortality was 73.6 ± 1.8%, but only 29.2 ± 1.9 and 10 ± 1.2% received surgical repair and transcatheter repair (TCR), respectively. TCR was associated with higher and surgical repair with lower mortality. Days to surgery were longer for those who survived (5.9 ± 2.75) compared with those who died (2.44 ± 1). In a multivariable analysis, surgical repair at greater than or equal to day 4 was associated with lower in-hospital mortality (odds ratio = 0.39, 95% confidence interval: 0.17-0.88)., Conclusion: Mortality in post-STEMI VSR remains high with no improvement over time. Most patients are managed conservatively, and the frequency of surgical repair has decreased, while TCR has increased over the study period. Despite design limitations and survival bias, surgical repair at greater than or equal to 4 days was associated with a lower mortality., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Despite key differences in pathological processes, both Intramural Hematomas and Aortic Dissections are Acute Aortic Syndromes repaired with similar surgical technique. The objective of this study was to determine differences in surgical outcomes between patients with Intramural Hematoma versus Type A Aortic Dissection undergoing Ascending Aortic Arch repair., Methods: This retrospective review of prospectively collected data included all patients with acute Intramural Hematoma or Type A Aortic Dissection who underwent emergent Ascending- or Arch Repair from January 2018 to May 2023 at a single academic institution. Primary outcomes included intraoperative mortality, 30-Day mortality, and postoperative stay. Secondary outcomes included postoperative complications. Outcomes were analyzed using Chi-squared, Fisher's Exact, and t-tests, with significance set at p < 0.05., Results: A total of 107 patients were included, 27 of whom (25%) had Intramural Hematoma and 80 (75%) had Type A Aortic Dissection. There were no differences in preoperative characteristics such as age, gender, and comorbidities, and no differences in perioperative characteristics such as case length, cardiopulmonary bypass, aortic cross-clamp, and circulatory arrest times. When comparing postoperative outcomes, there was a higher rate of postoperative pericardial effusions requiring pericardial window in the Intramural Hematoma cohort compared to the Aortic Dissection cohort (15% [n = 4] vs. 3% [n = 2]; p = 0.02). There were no differences in other primary outcomes such as intraoperative mortality, 30-Day mortality, and postoperative length of stay. There were also no differences in the rates of postoperative complications such as bleeding requiring reoperation, cerebrovascular accident, atrial fibrillation, pleural effusion requiring thoracentesis, and surgery-related Emergency Department visits., Conclusions: Our analysis demonstrates similar outcomes for patients undergoing Ascending Aortic Arch repair between patients with Intramural Hematoma and Type A Aortic Dissection. Despite the higher rate of required postoperative pericardial windows in the Intramural Hematoma cohort, the overall primary outcomes remained comparable. These findings better elucidate the standard of care for patients with acute Intramural Hematoma undergoing Ascending Aortic Arch repair., (© 2024. The Author(s).)

We describe a rare complication of intraprocedural spontaneous thrombus formation on a transcatheter edge-to-edge repair (MitraClip; Abbott Laboratories) device in a hypercoagulable yet adequately anticoagulated patient. We also outline the novel use of a vacuum (Penumbra) aspiration system, which resulted in rapid and effective thrombus elimination., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Dishcook is a new cooking system that allows individual cooking using a dedicated induction heater. This study investigated whether Dishcook use affects the nutritional value of individuals with intellectual disabilities. This study was conducted on users receiving support from a continuous-employment office in Obama City, Fukui Prefecture, in 2022. Of these participants, 18 (seven women and 11 men) who requested the use of the Dishcook were included in the analysis. The study period was from January to August 2023. The mean age was 48.72±16.24 y. A significant increase in the overall phase angles of the limbs was observed. Triglyceride, LDL cholesterol, HbA1c, and serum zinc levels improved in patients who used the Dishcook. The phase angle obtained using Bioelectrical Impedance Analysis also improved, indicating the usefulness of the Dishcook in treating metabolic diseases and the possibility of individualized nutritional management.

Introduction: We sought to compare outcomes after early discharge in patients with and without predischarge diagnosis of arrhythmia following minimally invasive valve surgery (MIVS)., Materials and Methods: We retrospectively reviewed ambulatory electrocardiography (AECG) datasheets and medical records of patients discharged with 14-d AECG monitoring from our facility between October 2019 and March 2022 ≤ 3 d after MIVS. Baseline and clinical characteristics, arrhythmias during AECG monitoring, and 30-d adverse outcomes were reported for the population and stratified by presence or absence of predischarge arrhythmia., Results: Of 41 patients discharged ≤3 d postoperatively of MIVS, 17 (41.5%) experienced predischarge arrhythmias and 24 (58.5%) did not. The population was predominantly male and White with a median age of 62 y [57, 70]. Baseline and clinical characteristics did not differ between subgroups. Most patients (92.7% [n = 38]) experienced one or more tachyarrhythmias during the AECG monitoring period. There were similar proportions of patients experiencing atrial fibrillation in both groups, but patients with predischarge arrhythmias had higher burden of atrial fibrillation on AECG monitoring (27.60% [6.57%, 100%] versus 1.65% [0.76%, 4.32%]; P = 0.004). The predischarge arrhythmia subgroup had higher proportions of patients experiencing nonsustained ventricular tachycardia but lower proportions experiencing supraventricular tachycardia. There were no mortalities within 30 d of surgery. Six (14.6%) patients were readmitted within 30 d with equal proportions of readmissions between subgroups (P = 0.662)., Conclusions: Early discharge timelines and noninvasive monitoring techniques can allow patients to return to their normal activities quicker in the comfort of their own home with no increased risk of morbidity or mortality., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To investigate the effect of minimally invasive cardiac surgery (MICS) on resource utilization, cost, and postoperative outcomes in patients undergoing left-heart valve operations., Methods: Data were retrospectively reviewed for patients undergoing single-valve surgery (eg, aortic valve replacement, mitral valve replacement, or mitral valve repair) at a single center from 2018 to 2021, stratified by surgical approach: MICS vs full sternotomy (FS). Baseline characteristics and postoperative outcomes were compared. Primary outcome was high resource utilization, defined as direct procedure cost higher than the third quartile or either postoperative LOS ≥7 days or 30-day readmission. Secondary outcomes were direct cost, length of stay, 30-day readmission, in-hospital and 30-day mortality, and major morbidity. Multiple regression analysis was conducted, controlling for baseline characteristics, operative approach, valve operation, and lead surgeon to assess high resource utilization., Results: MICS was correlated with a significantly lower rate of high resource utilization (MICS, 31.25% [n = 115] vs FS 61.29% [n = 76]; P  < .001). Median postoperative length of stay (MICS, 4 days [range, 3-6 days] vs FS, 6 days [range, 4 to 9 days]; P  < .001) and direct cost (MICS, $22,900 [$19,500-$28,600] vs FS, $31,900 [$25,900-$50,000]; P  < .001) were lower in the MICS group. FS patients were more likely to experience postoperative atrial fibrillation ( P  = .040) and renal failure ( P  = .027). Other outcomes did not differ between groups. Controlling for stratified Society of Thoracic Surgeons predicted risk of mortality, cardiac valve operation, and lead surgeon, FS demonstrated increased likelihood of high resource utilization ( P  < .001)., Conclusions: MICS for left-heart valve pathology demonstrated improved postoperative outcomes and resource utilization., (© 2023 The Author(s).)

Background: Establishing cardiopulmonary bypass remains critical to the successful repair of an acute type A aortic dissection. A recent trend away from femoral arterial cannulation has occurred in part due to concerns of stroke risk from retrograde perfusion to the brain. The purpose of this study was to determine if arterial cannulation site for aortic dissection repair impacts surgical outcomes., Methods: A retrospective chart review was performed at Rutgers Robert Wood Johnson Medical School from January 1st, 2011 to March 8th, 2021. Of the 135 patients included, 98 (73%) underwent femoral arterial cannulation, 21 (16%) axillary artery cannulation, and 16 (12%) direct aorta cannulation. The study variables included demographic data, cannulation site, and complications., Results: The mean age was 63.6±14 years, with no difference between the femoral, axillary, and direct cannulation groups. Eighty-four patients (62%) were male, with similar percentages amongst each group. The rates of bleeding, stroke, and mortality specifically due to the arterial cannulation did not significantly differ based on cannulation site. None of the patients had strokes that were attributable to cannulation type. No patients died as a direct complication of arterial access. The overall in-hospital mortality was 22%, similar between groups., Conclusions: This study found no statistically significant different in rates of stroke or other complications based on cannulation site. Femoral arterial cannulation thus remains a safe and efficient choice for arterial cannulation in the repair of acute type A aortic dissection., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-576/coif). The authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Objective: Over the last two decades there has been an increase in the number of cardiac implantable electronic devices and consequently, there has also been an increased need for lead extractions. Fibrotic attachments develop between the lead and the venous and cardiac structures that may require the use of a laser to mobilize the lead. Cardiothoracic surgeons (CTS) have traditionally provided backup for surgical emergencies for these extractions. This study evaluates the surgical outcomes of patients undergoing transvenous laser lead extractions (TLE) and determines if CTS are still needed for backup., Methods: A retrospective review of consecutive patients undergoing laser lead extractions at a single academic center. Lead extractions using only laser sheaths were analyzed. The clinical characteristics, complications, and mortality of the patients were evaluated., Results: One hundred and twenty-one patients underwent TLEs from January 1st, 2014 to December 31st, 2018. The majority were male (N = 80, 66.1%), and the average age was 66.48 ± 14 years. The indication for removal was either laser lead malfunction or infection. A total of 30 patients (24.8%) had complications postoperatively including wound hematomas, superficial infections, and arrhythmias. The average length of stay was 9 ± 12 for all the patients in the study. 2 patients (1.6%) had injuries that required emergency surgical repair with injuries to the posterior superior vena cava and right ventricle. Both patients survived the initial injury with one patient was discharged home on day 4 and the other succumbing to his injuries on postoperative day 20., Conclusion: Although the incidence of surgical emergencies is rare the morbidity and mortality for TLE require that surgical backup be available., (© 2022. The Author(s).)

Background: Empirical studies between anger and anger-provoking cognitive variables in children and adolescents are lacking, despite numerous studies on internalising and externalising problems., Aim: The purpose of this study was to develop new questionnaires for anger-provoking cognitive errors and automatic thoughts, and examine relationships between anger, cognitive errors, and automatic thoughts in children and adolescents., Method: Participants were 485 Japanese children and adolescents aged 9-15 years old (254 females; average age 12.07; SD = 1.81). They completed the Anger Children's Cognitive Error Scale (A-CCES) and the Anger Children's Automatic Thought Scale (A-CATS), which were developed in this study, as well as the Anger Scale for Children and Adolescents and the Japanese version of Short Spence Children's Anxiety Scale., Results: Both the A-CCES and the A-CATS had adequate reliability (internal consistency) and validity (face validity, structural validity and construct validity). A hierarchal regression analysis indicated that automatic thoughts were positively and moderately related to anger ( β = .37) after controlling for age, gender, anxiety symptoms, cognitive errors and interaction term. Moreover, a mediation analysis indicated that automatic thoughts significantly mediated the relationship between cognitive errors and anger (indirect effect, 0.24; 95% CI: .020 to .036)., Conclusions: This study developed the new questionnaires to assess anger-provoking cognitive errors and automatic thoughts. In addition, this study revealed that automatic thoughts rather than cognitive errors are associated with anger in children and adolescents.

Foreign bodies in the heart are a rare condition and an exact mechanism for this occurrence has not been well described. These objects can reach the heart by direct penetration due to local trauma or through intravenous migration or may remain in the heart after medical procedures. The most common foreign bodies that reach the heart are bullets and shrapnel. The purpose of this study is to review a case where a patient injected himself with recreational drugs. The needle subsequently dislodged from the syringe and migrated into the heart., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Lemaire et al.)

Delayed presentation of penetrating cardiac injuries is exceedingly rare due to the observed near 100% pre-hospital mortality. We describe a case of a patient who presented for evaluation nearly 24 h after sustaining a self-inflicted pneumatic nail gun injury to the right ventricular outflow tract. Remarkably, the patient had no evidence of hemodynamic compromise. This case highlights the importance of maintaining a high index of suspicion for cardiac injury with penetrating trauma to the cardiac box regardless of presenting signs and symptoms, and the value of adhering to advanced trauma life support principles., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. No funding was received to assist with this publication., (© 2021 The Authors.)

A 73-year-old male with a history of severe coronary artery disease and prior coronary artery bypass grafting (CABG) presented with chest pain and elevated troponins. His workup revealed an ejection fraction of 15%, severe native coronary disease, as well as stenosis of his bypass grafts. He underwent a high-risk redo CABG with an Impella 5.5® (Abiomed, Danvers, MA) placement. The device was removed on postoperative day eight, at which time he went into cardiogenic shock from aortic valve leaflet injury. Given that he had no calcium deposits around the aortic valve annulus and severe aortic insufficiency, a multidisciplinary heart team decided he would be best served by a surgical aortic valve replacement. He was taken back to the operating room for a surgical aortic valve and intra-aortic balloon pump. His postoperative course was complicated by pneumonia, sepsis, and renal failure requiring continuous renal replacement therapy. He was discharged to a rehabilitation facility after 42 days. The following case encompasses the high morbidity risk of acute aortic valve insufficiency after Impella placement, never before documented in an Impella 5.5., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Ghannam et al.)

Photoactivated adenylyl cyclase (PAC) is a unique protein that, upon blue light exposure, catalyzes cAMP production. The crystal structures of two PACs, from Oscillatoria acuminata (OaPAC) and Beggiatoa sp. (bPAC), have been solved, and they show a high degree of similarity. However, the photoactivity of OaPAC is much lower than that of bPAC, and the regulatory mechanism of PAC photoactivity, which induces the difference in activity between OaPAC and bPAC, has not yet been clarified. Here, we investigated the role of the C-terminal region in OaPAC, the length of which is the only notable difference from bPAC. We found that the photoactivity of OaPAC was inversely proportional to the C-terminal length. However, the deletion of more than nine amino acids did not further increase the activity, indicating that the nine amino acids at the C-terminal critically affect the photoactivity. Besides, absorption spectral features of light-sensing domains (BLUF domains) of the C-terminal deletion mutants showed similar light-dependent spectral shifts as in WT, indicating that the C-terminal region influences the activity without interacting with the BLUF domain. The study characterizes new PAC mutants with modified photoactivities, which could be useful as optogenetics tools.

Objective: Our study investigates the incidence, cumulative incidence, natural history, and factors associated with intraoperative paravalvular leak (PVL) and the development of a postoperative PVL in a contemporary consecutive cohort of patients following surgical aortic valve replacement. Methods: A total of 636 patients underwent surgical aortic valve replacement from 2006 to 2016; 410 (64.5%) underwent minimally invasive aortic valve replacement and 226 (35.5%) underwent conventional aortic valve replacement. Primary outcomes were the incidence of intraoperative PVL and cumulative incidence of postoperative PVL. Secondary outcomes were the incidence of in-hospital and long-term death and need for reoperation. Results: The overall incidence of intraoperative PVL was 1.4% (95% confidence interval [CI]: 1% to 3%). All intraoperative PVLs developed in the hand-tied group. The overall incidence of postoperative PVL was 5.3% (95% CI: 4% to 7%). In the univariable and multivariable analyses, postoperative renal failure was the only factor significantly associated with the development of a postoperative PVL. Conclusions: The incidence of intraoperative PVL is low. Cumulative incidence of postoperative PVL was 3.1% (95% CI: 1.0% to 13.6%), 4.3% (95% CI: 1.3% to 16.5%), and 5.0% (95% CI: 1.4% to 17.9%) at 1, 3, and 5 years, respectively. All intraoperative PVLs occurred with hand-tied knots. A larger cohort may identify additional risk factors.

Objectives: Patients with patent internal thoracic artery (ITA) grafts after prior coronary artery bypass grafting surgery who require aortic valve replacement (AVR) pose unique technical challenges for safe and optimal myocardial protection. The purpose of this study is to review our short- and long-term outcomes with redo minimally invasive AVR in patients with patent in situ ITA grafts., Methods: From 2008 to 2016, 48 patients with at least 1 patent in situ mammary artery graft underwent minimally invasive AVR. Preoperative computed tomography was performed in all patients to evaluate the relationship of patent grafts to the sternum. Retrograde coronary sinus and pulmonary vent catheters were placed via the right internal jugular vein. The in situ ITA grafts were not clamped during AVR. Transverse aortotomy, taking care to avoid the grafts arising from the aorta, was performed to expose the aortic valve., Results: The median age of the patients was 78 years [Quartile 1 (Q1)-Quartile 3 (Q3): 71-81]. Thirty-nine (81%) patients were men, and 46 (96%) patients had aortic stenosis. The median cardiopulmonary bypass and cross-clamp times were 124 (Q1-Q3: 108-164) and 92 (Q1-Q3: 83-116) min, respectively. Moderate hypothermia at 28-30°C was used in all patients. Most patients received cold blood cardioplegia with antegrade induction and continuous retrograde delivery. Four patients received only retrograde delivery due to some degree of aortic insufficiency. Thirty-day mortality was 4% (2 of 48 patients). There was no conversion to full sternotomy, and no reoperations were performed for postoperative bleeding or sternal wound infection. Excluding the 2 patients who died in the hospital, the median postoperative length of stay was 7 days (Q1-Q3: 5-8). Overall survival at 1, 5 and 10 years was 94%, 87% and 44%, respectively., Conclusions: Percutaneous retrograde cardioplegia combined with antegrade cardioplegia and moderate hypothermia, without interruption of ITA flow, is a safe and reliable strategy in patients with patent ITA grafts undergoing aortic valve replacement. This strategy combined with a minimally invasive approach may reduce surgical trauma, and is a safe and effective technique in these challenging patients., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Purpose: Decrease in activity stress induces skeletal muscle atrophy. A previous study showed that treatment with a high level (20%) of isoflavone inhibits muscle atrophy after short-term denervation (at 4 days) in mice. The present study was designed to elucidate whether the dietary isoflavone aglycone (AglyMax) at a 0.6% prevents denervation-mediated muscle atrophy, based on the modulation of atrogin-1- or apoptosis-dependent signaling., Methods: Mice were fed either a normal diet or 0.6% AglyMax diet. One week later, the right sciatic nerve was cut. The wet weight, mean fiber area, amount of atrogin-1 and cleaved caspase-3 proteins, and the percentages of apoptotic nuclei were examined in the gastrocnemius muscle at 14 days after denervation., Results: The 0.6% AglyMax diet significantly attenuated denervation-induced decreases in fiber atrophy but not the muscle wet weight. In addition, dietary isoflavone suppressed the denervation-induced apoptosis in spite of there being no significant changes in the amount of cleaved caspase-3 protein. In contrast, the 0.6% AglyMax diet did not significantly modulate the protein expression of atrogin-1 in the denervated muscle of mice., Conclusions: The isoflavone aglycone (AglyMax) at a 0.6% significantly would modulate muscle atrophy after denervation in mice, probably due to the decrease in apoptosis-dependent signaling.

Sepsis-associated encephalopathy (SAE), characterized as diffuse brain dysfunction and neurological manifestations secondary to sepsis, is a common complication in critically ill patients and can give rise to poor outcome, but understanding the molecular basis of this disorder remains a major challenge. Given the emerging role of G protein-coupled receptor 2 (GRK2), first identified as a G protein-coupled receptor (GPCR) regulator, in the regulation of non-G protein-coupled receptor-related molecules contributing to diverse cellular functions and pathology, including inflammation, we tested the hypothesis that GRK2 may be linked to the neuropathogenesis of SAE. When mouse MG6 microglial cells were challenged with lipopolysaccharide (LPS), GRK2 cytosolic expression was highly up-regulated. The ablation of GRK2 by small interfering RNAs (siRNAs) prevented an increase in intracellular reactive oxygen species generation in LPS-stimulated MG6 cells. Furthermore, the LPS-induced up-regulation of inducible nitric-oxide synthase expression and increase in nitric oxide production were negated by GRK2 inhibitor or siRNAs. However, GRK2 inhibition was without effect on overproduction of tumor necrosis factor-α, interleukin (IL)-6, and IL-1β in LPS-stimulated MG cells. In mice with cecal ligation and puncture-induced sepsis, treatment with GRK2 inhibitor reduced high levels of oxidative and nitrosative stress in the mice brains, where GRK2 expression was up-regulated, alleviated neurohistological damage observed in cerebral cortex sections, and conferred a significant survival advantage to CLP mice. Altogether, these results uncover the novel role for GRK2 in regulating cellular oxidative and nitrosative stress during inflammation and suggest that GRK2 may have a potential as an intriguing therapeutic target to prevent or treat SAE., (© 2018 International Society for Neurochemistry.)

Atrial fibrillation is associated with increased morbidity and mortality in patients undergoing mitral valve surgery. There is a growing consensus that patients with preexisting atrial fibrillation should undergo surgical ablation at the time of mitral valve surgery. Novel surgical ablation techniques, including cryoablation, have been developed to facilitate concurrent minimally invasive procedures. This video tutorial describes a combined cryo-maze procedure and mitral valve repair through an upper ministernotomy in a patient with long-standing persistent atrial fibrillation and severe mitral regurgitation., (© The Author 2016. Published by MMCTS on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Degenerative mitral valve disease is associated with variable and complex defects in valve morphology. Three-dimensional echocardiography (3DE) has shown promise in aiding preoperative planning for patients with this disease but to date has not been as transformative as initially predicted. The clinical usefulness of 3DE has been limited by the laborious methods currently required to extract quantitative data from the images., Methods: To maximize the utility of 3DE for preoperative valve evaluation, this work describes an automated 3DE image analysis method for generating models of the mitral valve that are well suited for both qualitative and quantitative assessment. The method is unique in that it captures detailed alterations in mitral leaflet and annular morphology and produces image-derived models with locally varying leaflet thickness. The method is evaluated on midsystolic transesophageal 3DE images acquired from 22 subjects with myxomatous degeneration and from 22 subjects with normal mitral valve morphology., Results: Relative to manual image analysis, the automated method accurately represents both normal and complex leaflet geometries with a mean boundary displacement error on the order of one image voxel. A detailed quantitative analysis of the valves is presented and reveals statistically significant differences between normal and myxomatous valves with respect to numerous aspects of annular and leaflet geometry., Conclusions: This work demonstrates a successful methodology for the relatively rapid quantitative description of the complex mitral valve distortions associated with myxomatous degeneration. The methodology has the potential to significantly improve surgical planning for patients with complex mitral valve disease., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Cyclic-AMP is one of the most important second messengers, regulating many crucial cellular events in both prokaryotes and eukaryotes, and precise spatial and temporal control of cAMP levels by light shows great promise as a simple means of manipulating and studying numerous cell pathways and processes. The photoactivated adenylate cyclase (PAC) from the photosynthetic cyanobacterium Oscillatoria acuminata (OaPAC) is a small homodimer eminently suitable for this task, requiring only a simple flavin chromophore within a blue light using flavin (BLUF) domain. These domains, one of the most studied types of biological photoreceptor, respond to blue light and either regulate the activity of an attached enzyme domain or change its affinity for a repressor protein. BLUF domains were discovered through studies of photo-induced movements of Euglena gracilis, a unicellular flagellate, and gene expression in the purple bacterium Rhodobacter sphaeroides, but the precise details of light activation remain unknown. Here, we describe crystal structures and the light regulation mechanism of the previously undescribed OaPAC, showing a central coiled coil transmits changes from the light-sensing domains to the active sites with minimal structural rearrangement. Site-directed mutants show residues essential for signal transduction over 45 Å across the protein. The use of the protein in living human cells is demonstrated with cAMP-dependent luciferase, showing a rapid and stable response to light over many hours and activation cycles. The structures determined in this study will assist future efforts to create artificial light-regulated control modules as part of a general optogenetic toolkit.

Deformable modeling with medial axis representation is a useful means of segmenting and parametrically describing the shape of anatomical structures in medical images. Continuous medial representation (cm-rep) is a "skeleton-first" approach to deformable medial modeling that explicitly parameterizes an object's medial axis and derives the object's boundary algorithmically. Although cm-rep has effectively been used to segment and model a number of anatomical structures with non-branching medial topologies, the framework is challenging to apply to objects with branching medial geometries since branch curves in the medial axis are difficult to parameterize. In this work, we demonstrate the first clinical application of a new "boundary-first" deformable medial modeling paradigm, wherein an object's boundary is explicitly described and constraints are imposed on boundary geometry to preserve the branching configuration of the medial axis during model deformation. This "boundary-first" framework is leveraged to segment and morphologically analyze the aortic valve apparatus in 3D echocardiographic images. Relative to manual tracing, segmentation with deformable medial modeling achieves a mean boundary error of 0.41 ± 0.10 mm (approximately one voxel) in 22 3DE images of normal aortic valves at systole. Deformable medial modeling is additionally demonstrated on pathological cases, including aortic stenosis, Marfan syndrome, and bicuspid aortic valve disease. This study demonstrates a promising approach for quantitative 3DE analysis of aortic valve morphology., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: There is continued need for therapies which reverse or abate the remodeling process after myocardial infarction (MI). In this study, we evaluate the longitudinal effects of calcium hydroxyapatite microsphere gel on regional strain, global ventricular function, and mitral regurgitation (MR) in a porcine MI model., Methods: Twenty-five Yorkshire swine were enrolled. Five were dedicated weight-matched controls. Twenty underwent posterolateral infarction by direct ligation of the circumflex artery and its branches. Infarcted animals were randomly divided into the following 4 groups: 1-week treatment; 1-week control; 4-week treatment; and 4-week control. After infarction, animals received either twenty 150 μL calcium hydroxyapatite gel or saline injections within the infarct. At their respective time points, echocardiograms, cardiac magnetic resonance imaging, and tissue were collected for evaluation of MR, regional and global left ventricular function, wall thickness, and collagen content., Results: Global and regional left ventricular functions were depressed in all infarcted subjects at 1 week compared with healthy controls. By 4-weeks post-infarction, global function had significantly improved in the calcium hydroxyapatite group compared with infarcted controls (ejection fraction 0.485 ± 0.019 vs 0.38 ± 0.017, p < 0.01). Similarly, regional borderzone radial contractile strain (16.3% ± 1.5% vs 11.2% ± 1.5%, p = 0.04), MR grade (0.4 ± 0.2 vs 1.2 ± 0.2, p = 0.04), and infarct thickness (7.8 ± 0.5 mm vs 4.5 ± 0.2 mm, p < 0.01) were improved at this time point in the treatment group compared with infarct controls., Conclusions: Calcium hydroxyapatite injection after MI progressively improves global left ventricular function, borderzone function, and mitral regurgitation. Using novel biomaterials to augment infarct material properties is a viable alternative in the current management of heart failure., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Epigenetic programming, dynamically regulated by histone acetylation, may play a key role in the pathophysiology of sepsis. We examined whether histone deacetylase (HDAC) can contribute to sepsis-associated inflammation and apoptosis., Materials and Methods: Polymicrobial sepsis was induced by cecal ligation and puncture (CLP) in BALB/c mice. An intraperitoneal injection of CG200745 (10 mg/kg), a novel broad-spectrum HDAC inhibitor, or valproic acid (500 mg/kg), a predominant inhibitor of class I HDACs, was given 3 h before surgery., Results: HDAC1, HDAC2, and HDAC3 protein levels were decreased in lungs after CLP. Furthermore, CLP-induced sepsis increased both histone H3 and H4 acetylation levels in lungs. When CG200745 was given, apoptosis induction was strongly suppressed in lungs and spleens of septic mice. This antiapoptotic effect of CG200745 was not accompanied by upregulation of antiapoptotic and downregulation of proapoptotic Bcl-2 family member proteins. Treatment with CG200745 failed to inhibit elevated levels of serum cytokines and prevent lung inflammation in septic mice. Valproic acid also showed antiapoptotic but not anti-inflammatory effects in septic mice., Conclusions: These findings imply that HDAC inhibitors are a unique agent to prevent cell apoptosis in sepsis at their doses that do not improve inflammatory features, indicating that septic inflammation and apoptosis may not necessarily be essential for one another's existence. This study also represents the first report that CLP-induced sepsis downregulates HDACs. Nevertheless, the data with HDAC inhibitors suggest that imbalance in histone acetylation may play a contributory role in expression or repression of genes involved in septic cell apoptosis., (Copyright © 2014 Elsevier Inc. All rights reserved.)