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Objective Transcarotid access for transcatheter aortic valve replacement is emerging as an alternative to more traditional nonfemoral access options such as transapical or transaortic; however, comparative data are limited. The purpose of the study was to analyze outcomes after transcatheter aortic valve replacement using transcatheter compared with transthoracic (transapical/transaortic) access. Methods The Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry was queried for patients who underwent transcarotid, transapical, or transaortic transcatheter aortic valve replacement with the SAPIEN 3 (Edwards Lifesciences, Irvine, Calif) transcatheter heart valve between June 2015 and July 2019. Thirty-day unadjusted outcomes were evaluated, and propensity score matching and logistic regression were used to compare transcatheter access with transthoracic access. Results In the propensity-matched analysis, 667 transcarotid transcatheter aortic valve replacement procedures were compared with 1334 transthoracic procedures. Transcarotid transcatheter aortic valve replacement was associated with lower mortality (4.2% vs 7.7%, P = .004), less new-onset atrial fibrillation (2.2% vs 12.1%, P Conclusions Transcatheter aortic valve replacement using transcarotid access is associated with lower 30-day mortality, less atrial fibrillation, shorter intensive care unit and overall length of stay, fewer readmissions, greater improvement in Kansas City Cardiomyopathy Questionnaire scores, and no significant difference in stroke or major vascular complications compared with transthoracic access.

With continued growth of transcatheter aortic valve replacement (TAVR), safe alternative access remains important for patients without adequate transfemoral (TF) access. Registry-based outcomes with transcarotid (TC) TAVR are favorable compared to transapical or transaxillary/subclavian, but TC vs TF comparisons have not been made. Our objective was to compare outcomes between TF and TC access routes for TAVR at a high-volume United States center. Methods: We retrospectively evaluated all TF and TC TAVR procedures from June 11, 2014 (first TC case) through December 31, 2019. The primary outcomes were 30-day stroke and 30-day mortality. Secondary outcomes were 1-year stroke, 1-year survival, and 30-day and 1-year life-threatening/major bleeding, vascular complications, and myocardial infarction. Propensity score weighted (PSW) models were used to compare risk-adjusted TF and TC outcomes. Of 1,465 TAVR procedures, 1319 (90%) were TF and 146 (10%) were TC. Procedure time and length of stay did not differ between groups. Unadjusted 30-day stroke (TF = 2.0%, TC = 2.7%, P = 0.536) and mortality (TF = 2.1%, TC = 2.7%, P = 0.629) were similar between groups. PSW 30-day stroke (odds ratio (OR) (95% confidence interval (CI)) = 0.8 (0.2-2.8)) and mortality (OR (95% CI) = 0.8 (0.2-3.0)) were similar between groups. Unadjusted and PSW 30-day major/life threatening bleeding, major vascular complications, and myocardial infarction did not differ between groups. Survival at one year was 90% (88%-92%) for TF patients and 87% (81%-93%) for TC patients (unadjusted P = 0.28, PSW hazard ratio = 1.0 (0.6-1.7)). Transcarotid TAVR is associated with similar outcomes compared to transfemoral TAVR at an experienced, high-volume center.

Subclavian/axillary (TAx) access has become the most frequently used alternative access route for transcatheter aortic valve replacement (TAVR). Transcarotid (TC) TAVR has grown in popularity recently. Comparative data between these 2 contemporary access methods is lacking.Data were extracted from The Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (TVT) Registry™ (June 2015 to October 2019) for patients undergoing TAVR by TC or TAx access with the SAPIEN 3 and SAPIEN 3 Ultra (Edwards Lifesciences, Irvine, CA) transcatheter heart valves. Procedural, index hospitalization, and 30-day outcomes were analyzed for TC vs TAx groups after 1:2 propensity matching of patient baseline characteristics.The study included 3903 cases, of which 801 TC and 3102 TAx procedures were compared. After 1:2 propensity matching, TC TAVR was associated with similar 30-day mortality (4.3% vs 5.2%, P = .34) but a significantly lower risk of stroke (4.2% vs 7.4%; hazard ratio, 0.56; 95% confidence interval, 0.38-0.83; P = .003) compared with TAx access. Other outcomes that favored TC over TAx included shorter procedure time (117.0 vs 132.4 minutes; P.001) and fluoroscopy time (16.6 vs 21.6 min; P.001), lower contrast volume (78.5 vs 96.7 mL; P.001), shorter length of stay in the intensive care unit (24.3 vs 25.0 hours; P = .02) and hospital (2.0 vs 3.0 days; P = .002), and more patients discharged to home (82.9% vs 74.6%; P.001).TC TAVR is associated with similar mortality and a significant reduction in stroke compared with the TAx approach. If femoral access is precluded, TC may be a safe, or at times, preferred avenue of transcatheter valve delivery.

There are limited invasive treatment options for patients with end-stage heart failure and left ventricular assist device (LVAD) who develop severe aortic valve regurgitation (AR). One option for such patients is transcatheter aortic valve replacement (TAVR). There are limited data on outcomes of patients with LVAD who receive TAVR for severe AR. We present a series of 4 consecutive patients with LVAD who underwent TAVR for severe AR.This is a retrospective chart review of 4 consecutive patients with LVAD who underwent TAVR for severe AR. All 4 patients underwent TAVR with a 34-mm self-expanding valve (Medtronic). One patient received a 29-mm balloon-expandable valve (Edwards Lifesciences) within the self-expanding valve (SEV) to postdilate the SEV and minimize paravalvular leak (PVL). All 4 procedures were technically successful. The patient who received rescue valve-in-valve TAVR continued to have persistent mild to moderate PVL.Although technically challenging, TAVR is a feasible option for carefully selected LVAD patients with severe AR. Procedural issues to consider include oversizing the transcatheter heart valve (THV) while being cognizant of the risks of annular rupture and valve dislocation, anticipating and avoiding ventricular migration of the THV and being ready to postdilate the THV if necessary, to limit hemodynamically significant PVL.

Background The COVID-19 pandemic has disrupted routine cardiovascular care, with unclear impact on procedural deferrals and associated outcomes across diverse patient populations. Methods Cardiovascular procedures performed at 30 hospitals across six Western states in two large, non-profit healthcare systems (Providence St. Joseph Health and Stanford Healthcare) from December 2018-June 2020 were analyzed for changes over time. Risk-adjusted in-hospital mortality was compared across pandemic phases with multivariate logistic regression. Results Among 36,125 procedures (69% percutaneous coronary intervention, 13% coronary artery bypass graft surgery, 10% transcatheter aortic valve replacement, and 8% surgical aortic valve replacement), weekly volumes changed in two distinct phases after the initial inflection point on February 23, 2020: an initial period of significant deferral (COVID I: March 15 to April 11) followed by recovery (COVID II: April 12 onwards). Compared to pre-COVID, COVID I patients were less likely to be female (p=0.0003), older (p, Graphical Abstract Image, graphical abstract

Stroke has long been a devastating complication of any cardiovascular procedure that unfavorably affects survival and quality of life. Over time, strategies have been developed to substantially reduce the incidence of stroke after traditional cardiovascular procedures such as coronary artery bypass grafting, isolated valve surgery, and carotid endarterectomy. Subsequently, with the advent of minimally invasive technologies including percutaneous coronary intervention, carotid artery stenting, and transcatheter valve therapies, operators were faced with a new host of procedural risk factors, and efforts again turned toward identifying novel ways to reduce the risk of stroke. Fortunately, by understanding the procedural factors unique to these new techniques and applying many of the lessons learned from prior experiences, we are seeing significant improvements in the safety of these new technologies. In this review, the authors: 1) carefully analyze data from different cardiac procedural experiences ranging from traditional open heart surgery to percutaneous coronary intervention and transcatheter valve therapies; 2) explore the unique risk factors for stroke in each of these areas; and 3) describe how these risks can be mitigated with improved patient selection, adjuvant pharmacotherapy, procedural improvements, and novel technological advancements.

Infections involving internal cardiac devices can be very challenging to treat, and almost universally require complete device extraction for successful management. Of the pathogens that cause device-related endocarditis, fungi such as Candida albicans are notoriously difficult to manage because of their propensity to produce large vegetations and the need for long-term treatment with potentially toxic medications. Furthermore, individuals who develop fungal, device-associated endocarditis are typically among the most complex patients, with significant comorbidities that place them at high risk for open heart procedures such as surgical device extraction. We present a case of one such patient in whom treatment of Candida albicans device-related endocarditis was managed using AngioVac® aspiration of a large right atrial vegetation with simultaneous laser sheath extraction of the implantable cardioverter-defibrillator lead.

Stroke is a devastating, potential complication of any cardiovascular procedure including transcatheter aortic valve implantation (TAVI). Even clinically silent lesions as detected by magnetic resonance imaging have been associated with poor long-term cognitive outcomes. As a result, extensive efforts have been focused on developing stroke preventative strategies including the development of novel embolic protection devices. These devices aim to reduce this risk by capturing or deflecting emboli away from the cerebral circulation. Areas covered: This review provides an insight into the incidence and mechanisms of neurologic events during TAVI, explores the design features and initial human experience of each of the cerebral embolic protection devices that have been used during TAVI, and carefully explains the major clinical trials of each of these devices with a focus on safety, efficacy and other reported outcomes. Expert commentary: The potential benefit of neuroprotection cannot be ignored as TAVI widens its scope to include younger and lower-risk patients wherein preventing a procedure related cerebral injury would potentially prevent long-term morbidity and mortality.

OBJECTIVES To develop a protocol for using a pre-existing, permanent pacemaker or defibrillator device for rapid ventricular pacing during transcatheter valve procedures and demonstrate feasibility. BACKGROUND Placement of a passive fixation, temporary pacemaker wire is considered routine during most transcatheter valve procedures to facilitate controlled or rapid ventricular pacing at the time of balloon expansion or valve deployment. Many patients presenting for such procedures have a pre-existing, permanent pacemaker or defibrillator device which could be used for the same function, obviating the need for temporary pacemaker wire placement. METHODS We developed a strategy for rapid pacing from the pre-existing device using a programmer during transcatheter valve procedures in consecutive patients over a 3-month period. Complications and clinical outcomes were recorded. RESULTS There were 135 transcatheter valve procedures performed during the study. Of these, 28 (20.7%) had pre-existing devices (17 transcatheter aortic valve replacement, 3 aortic valve-in-valve, 2 mitral valve-in-valve, and 6 balloon aortic valvuloplasty). All patients underwent rapid ventricular pacing using a commercially available device programmer. There were no adverse events related to device pacing and no patients required placement of a temporary pacemaker wire during the procedure. At 30-days follow-up, there were no deaths, one major vascular complication related to arterial access, and one patient with renal failure requiring dialysis. CONCLUSION Pacing from a commercially available device programmer is safe, feasible, and may reduce both procedural cost and complications such as cardiac tamponade by avoiding placement of a temporary pacemaker lead during transcatheter valve procedures.

Aortic stenosis (AS) is an increasingly common problem in developed countries. While surgical aortic valve replacement (SAVR) has long been the gold standard for managing severe, symptomatic AS, there has been a significant shift in the age and complexity of patients requiring intervention, and as a result, an increasing number of patients are not candidates for surgery. Transcatheter aortic valve replacement (TAVR) has developed into a vital alternative for inoperable patients and has shown excellent results in high- and even moderate-risk populations. As the technology has evolved over more than a decade since the first in-human TAVR, the procedure itself has become in many ways routine, has shown excellent safety, and has been adopted by hundreds of hospitals throughout the world. Despite this rapid expansion of TAVR technology, the patient population remains very complex, and individuals frequently have significant comorbid conditions that make TAVR anything but routine. Therefore, the goal of this chapter is to discuss the management of especially high-risk or atypical patients requiring TAVR, how to approach uncommon anatomy or comorbid conditions, and the management of unusual procedural complications.

With the extirpation of apex predators from many North American systems, coyotes Canis latrans have become the de facto top predator and are ubiquitous members of most ecosystems. Keystone predators aid in maintaining ecosystem function by regulating the mammal community through direct predation and instilling the landscape of fear, yet the value of coyotes regulating systems to this capacity is understudied and likely variable across environments. Since coyotes are common in the Midwestern United States, we utilized camera traps and occupancy analyses to assess their role in regulating the distribution of mammalian herbivores in a fragmented suburban ecosystem. Forest cover was a strong positive predictor of white-tailed deer Odocoileus virginianus detection, while coyote occurrence had a negative effect. Coyotes exerted a negative effect on squirrel (Sciurus spp.) and eastern cottontail rabbit Sylvilagus floridanus occurrence, while urban cover was a positive predictor for the prey species’ occurrence. These results suggest all 3 species behaviorally avoid coyotes whereby deer seek denser forest cover and squirrels and cottontails mitigate risk by increasing use of urban areas. Although previous studies reveal limited influence of coyote on the rest of the carnivore guild in suburban systems, we suggest coyotes play an important role in regulating the herbivorous mammals and hence may provide similar ecological benefits in urban/suburban forest fragments through trophic cascades. Furthermore, since hunting may not be allowed in urban and suburban habitats, coyotes might also serve as the primary regulator of nuisance species occurring at high abundance such as white-tailed deer and squirrels.

DEPDC5 is a newly identified epilepsy-related gene implicated in focal epilepsy, brain malformations, and Sudden Unexplained Death in Epilepsy (SUDEP). In vitro, DEPDC5 negatively regulates amino acid sensing by the mTOR complex 1 (mTORC1) pathway, but the role of DEPDC5 in neurodevelopment and epilepsy has not been described. No animal model of DEPDC5-related epilepsy has recapitulated the neurological phenotypes seen in patients, and germline knockout rodent models are embryonic lethal. Here, we establish a neuron-specific Depdc5 conditional knockout mouse by cre-recombination under the Synapsin1 promotor. Depdc5 flox/flox -Syn1 Cre (Depdc5cc+) mice survive to adulthood with a progressive neurologic phenotype that includes motor abnormalities (i.e., hind limb clasping) and reduced survival compared to littermate control mice. Depdc5cc+ mice have larger brains with increased cortical neuron size and dysplastic neurons throughout the cortex, comparable to the abnormal neurons seen in human focal cortical dysplasia specimens. Depdc5 results in constitutive mTORC1 hyperactivation exclusively in neurons as measured by the increased phosphorylation of the downstream ribosomal protein S6. Despite a lack of increased mTORC1 signaling within astrocytes, Depdc5cc+ brains show reactive astrogliosis. We observed two Depdc5cc+ mice to have spontaneous seizures, including a terminal seizure. We demonstrate that as a group Depdc5cc+ mice have lowered seizure thresholds, as evidenced by decreased latency to seizures after chemoconvulsant injection and increased mortality from pentylenetetrazole-induced seizures. In summary, our neuron-specific Depdc5 knockout mouse model recapitulates clinical, pathological, and biochemical features of human DEPDC5-related epilepsy and brain malformations. We thereby present an important model in which to study targeted therapeutic strategies for DEPDC5-related conditions.

Stroke has long been a devastating complication of any cardiovascular procedure that unfavorably affects survival and quality of life. Over time, strategies have been developed to substantially reduce the incidence of stroke after traditional cardiovascular procedures such as coronary artery bypass grafting, isolated valve surgery, and carotid endarterectomy. Subsequently, with the advent of minimally invasive technologies including percutaneous coronary intervention, carotid artery stenting, and transcatheter valve therapies, operators were faced with a new host of procedural risk factors, and efforts again turned toward identifying novel ways to reduce the risk of stroke. Fortunately, by understanding the procedural factors unique to these new techniques and applying many of the lessons learned from prior experiences, we are seeing significant improvements in the safety of these new technologies. In this review, the authors: 1) carefully analyze data from different cardiac procedural experiences ranging from traditional open heart surgery to percutaneous coronary intervention and transcatheter valve therapies; 2) explore the unique risk factors for stroke in each of these areas; and 3) describe how these risks can be mitigated with improved patient selection, adjuvant pharmacotherapy, procedural improvements, and novel technological advancements.

Patient: Female, 60Final Diagnosis: Pulmonary vein stenosis following single lung transplantSymptoms: Dyspnea on exertion and dry coughMedication: —Clinical Procedure: Balloon angioplasty and stenting of the left common pulmonary veinSpecialty: Cardiology Objective: Unusual clinical course Background: Pulmonary vein stenosis (PVS) is a rare event following lung transplantation, but is a serious complication that requires prompt diagnosis and treatment. Case Report: We describe the case of a 60-year-old woman who underwent single-lung transplantation for idiopathic pulmonary fibrosis (IPF). One year following her single-lung transplant, she was admitted to the hospital for hypoxemic respiratory failure. The results of quantitative lung perfusion scintigraphy (LPS) raised the possibility of a diagnosis of PVS. Computed tomography angiography (CT angiography) of the chest identified more than 50% stenosis of the left common pulmonary vein at the anastomotic site with the left atrium. She was successfully treated with angioplasty and stent placement guided by intravascular ultrasonography. Post dilatation of the PVS, the pulmonary venous pressure gradient decreased from 12–16 mm Hg to 3–4 mm Hg. At three-month follow-up, the patient reported resolution of her shortness of breath. In support of this case report, we review the management of four previously reported cases from the literature of lung transplantation associated with PVS. Conclusions: PVS should be considered in the differential diagnosis of lung transplant patients who present with worsening dyspnea. Quantitative LPS and CT angiography are important in the diagnosis of PVS. Successful management of PVS, with salvage of the transplanted lung and the prevention of further surgical interventions, may be achieved with intravascular ultrasound-guided angioplasty and stent placement.

Background The impact of coronary artery disease ( CAD ) on outcomes after transcatheter aortic valve replacement ( TAVR ) is understudied. Literature on the prognostic role of CAD in the survival of patients undergoing TAVR shows conflicting results. This meta‐analysis aims to investigate how CAD impacts patient survival following TAVR . Methods and Results We completed a comprehensive literature search of Embase, MEDLINE , and the Cochrane Library, and included studies reporting outcome of TAVR based on CAD status of patients for the analysis. From the initial 1631 citations, 15 studies reporting on 8013 patients were analyzed using a random‐effects model. Of the 8013 patients undergoing TAVR , with a median age of 81.3 years (79–85.1 years), 46.6% (40–55.7) were men and 3899 (48.7%) had CAD (ranging from 30.8% to 78.2% in various studies). Overall, 3121 SAPIEN / SAPIEN XT / SAPIEN 3 (39.6%) and 4763 CoreValve (60.4%) prostheses were implanted, with transfemoral access being the most frequently used approach for the implantation (76.1%). Our analysis showed no significant difference between patients with and without CAD for all‐cause mortality at 30 days post TAVR , with a cumulative odds ratio of 1.07 (95% confidence interval, 0.82–1.40; P= 0.62). However, there was a significant increase in all‐cause mortality at 1 year in the CAD group compared with patients without CAD , with a cumulative odds ratio of 1.21 (95% confidence interval, 1.07–1.36; P =0.002). Conclusions Even though coexisting CAD does not impact 30‐day mortality, it does have an impact on 1‐year mortality in patients undergoing TAVR . Our results highlight a need to revisit the revascularization strategies for concomitant CAD in patients with TAVR.

Transcatheter aortic valve implantation (TAVI) has become a widely accepted strategy for the treatment of aortic stenosis in patients at intermediate, high, or prohibitive surgical risk. After >1 decade of innovation and clinical trial experience, the available technology for TAVI has grown enormously, and now includes a myriad of vascular access approaches and innovative valve designs. As a result, the range of patients who can benefit from these advances continues to grow rapidly. Furthermore, given the improved safety profile and clinical success of current-generation devices in randomized trials, the use of TAVI among even low-risk populations is justified in current trials. With the rapid dissemination and expansion of this technology, operators need to have a comprehensive understanding of how to select the appropriate procedural approach for each individual patient. In this Review, we detail the current evidence for TAVI among different patient populations, discuss the different vascular access approaches currently in use, and explore differences in design features among currently available and investigational valve systems. Furthermore, we provide an overview of important considerations for special patient populations, such as those with existing mitral prostheses, bicuspid aortic stenosis, isolated aortic regurgitation, or severe left ventricular outflow tract calcification.

Early trials involving transcatheter aortic valve replacement raised concerns for an elevated risk of neurologic events compared to surgical AVR. Contemporary studies suggest declining rates with better patient selection, improved operator experience, and newer generation devices. Events are usually embolic in nature, occur in the periprocedural period, and can lead to increased morbidity and mortality. Current investigations are focused on developing embolic protection devices for intraprocedural use and optimizing antiplatelet and anticoagulant regimens. These efforts aim to further reduce the incidence of stroke, which is particularly important as the technology expands to include intermediate and possibly low surgical risk populations.

Hypertrophic cardiomyopathy (HCM) is a complex and heterogeneous disease with different anatomical variants, physiologic manifestations, and genetic underpinnings. Even asymptomatic patients with HCM are at potential risk for sudden cardiac death and require risk stratification and consideration of

This is a case of a 61 year old woman with chest discomfort and evidence of an inferior, ST-elevation myocardial infarction, who develops persistent cardiogenic shock and respiratory failure after primary percutaneous coronary intervention. We discuss the differential diagnosis for cardiogenic shock after acute myocardial infarction (AMI) including left ventricular failure, right ventricular failure, iatrogenic causes such as over-medication or bleeding complications, and mechanical complications of AMI including ventricular septal rupture (VSR), papillary muscle rupture, and free-wall rupture with cardiac tamponade. We focus on modalities for making the diagnosis including physical exam findings, trans-thoracic echocardiography, left ventriculogram, and right-heart catheterization. Medical as well as surgical management is discussed. Finally, we explore the controversial aspects regarding the evidence for intra-aortic balloon pump use in patients with cardiogenic shock after AMI, the optimal timing of surgical repair for VSR, and percutaneous options for VSR closure.

Amyloid is a generic term for insoluble, often intensely hydrophobic, fibrous protein aggregates that arise from inappropriately folded versions of naturally-occurring polypeptides. The abnormal generation and accumulation of amyloid, often referred to as amyloidogenesis, has been associated with the immune and pro-inflammatory pathology of several progressive age-related diseases of the human central nervous system (CNS) including Alzheimer's disease (AD) and age-related macular degeneration (AMD). This 'research perspective' paper reviews some of the research history, biophysics, molecular-genetics and environmental factors concerning the contribution of amyloid beta (Aβ) peptides, derived from beta-amyloid precursor protein (βAPP), to AD and AMD that suggests an extensive similarity in immune and inflammatory degenerative mechanisms between these two CNS diseases.

Ventricular septal rupture (VSR) after acute myocardial infarction is increasingly rare in the percutaneous coronary intervention era but mortality remains high. Prompt diagnosis is key and definitive surgery, though challenging and associated with high mortality, remains the treatment of choice. Alternatively, delaying surgery in stable patients may provide better results. Prolonged medical management is usually futile, but includes afterload reduction and intra-aortic balloon pump placement. Using full mechanical support to delay surgery is an attractive option, but data on success is limited to case reports. Finally, percutaneous VSR closure may be used as a temporizing measure to reduce shunt, or for patients in the sub-acute to chronic period whose comorbidities preclude surgical repair.

Moderate to severe aortic regurgitation after transcatheter aortic valve replacement is associated with worse outcomes. The impact of mild aortic regurgitation has been less clear, possibly because of the broad categories that have been used in clinical trials, but holds increasing importance in the study of next-generation devices in low- and intermediate-risk cohorts. A more granular scheme, which is common in clinical practice and proposed for future trials, may add prognostic value.We evaluated all patients undergoing transfemoral transcatheter aortic valve replacement at the Cleveland Clinic from 2006 to 2012. The degree of aortic regurgitation after transcatheter aortic valve replacement was reported from the echocardiography database based on a clinical, transthoracic echocardiogram performed within 30 days of the procedure. Aortic regurgitation was finely discriminated on the basis of a multiwindow, multiparametric, integrative approach using our usual clinical scale: none, trivial to 1+, 1+, 1 to 2+, 2+, 2 to 3+, 3+, 3 to 4+, or 4+.There were 237 patients included in the analysis. By controlling for age, gender, Society of Thoracic Surgeons score, baseline ejection fraction, and aortic regurgitation before transcatheter aortic valve replacement, there was a significant increase in mortality for each half grade of aortic regurgitation compared with the complete absence of aortic regurgitation after transcatheter aortic valve replacement. The unit hazard ratio for each 1+ increase in aortic regurgitation after transcatheter aortic valve replacement was 2.26 (95% confidence interval, 1.48-3.43; P .001) considering aortic regurgitation as a continuous variable. Other clinical variables did not significantly affect mortality.Even mild aortic regurgitation after transcatheter aortic valve replacement is associated with worse long-term mortality. There may be prognostic value in reporting milder categories of aortic regurgitation with more granular gradations.

The mesopredator release hypothesis (MRH) has been suggested as a reason why many mammalian generalist mesopredators flourish and become abundant. However, the MRH has only been examined in a limited number of field studies. Some studies have argued that coyotes (Canis latrans) act as top predators in fragmented forest systems and coyote presence has a positive effect on song bird diversity and abundance by controlling mesopredator abundance. We integrated camera trap data and occupancy modeling to determine the factors that affect coyote detection probability and habitat use in a fragmented suburban landscape in central Missouri. We then examined the influence of coyote presence and other habitat variables on mesopredator detection probability and habitat use in the same system. Coyote detection was negatively related to increasing forest cover, whereas red fox (Vulpes vulpes) detection was positively related to increasing urbanization. Coyote occurrence models suggested little habitat selection...

Evolution of reactive oxygen species (ROS), generated during the patho-physiological stress of nervous tissue, has been implicated in the etiology of several progressive human neurological disorders including Alzheimer’s disease (AD) and amylotrophic lateral sclerosis (ALS). In this brief communication we used mixed isomers of 5-(and-6)-carboxy-2′,7′-dichlorofluorescein diacetate (carboxy-DCFDA; C25H14Cl2O9; MW 529.3), a novel fluorescent indicator, to assess ROS generation within human neuronal-glial (HNG) cells in primary co-culture. We introduced pathological stress using the sulfates of 12 environmentally-, industrially- and agriculturally-relevant divalent and trivalent metals including Al, Cd, Cu, Fe, Hg, Ga, Mg, Mn, Ni, Pb, Sn and Zn. In this experimental test system, of all the metal sulfates analyzed, aluminum sulfate showed by far the greatest ability to induce intracellular ROS. These studies indicate the utility of using isomeric mixtures of carboxy-H2DCFDA diacetates as novel and highly sensitive, long-lasting, cell-permeant, fluorescein-based tracers for quantifying ROS generation in intact, metabolizing human brain cells, and in analyzing the potential epigenetic contribution of different metal sulfates to ROS-generation and ROS-mediated neurological dysfunction.

AimTo assess plasma zinc and copper concentration in individuals with autism and correlate these levels with symptom severity.Subjects and MethodsPlasma from 102 autistic individuals, and 18 neurotypical controls, were tested for plasma zinc and copper using inductively-coupled plasma-mass spectrometry. Copper and zinc levels and Cu/Zn were analyzed for possible correlation with severity of 19 symptoms.ResultsAutistic individuals had elevated plasma levels of copper and Cu/Zn and lower, but not significantly lower, plasma Zn compared to neurotypical controls. There was a correlation between Cu/Zn and expressive language, receptive language, focus attention, hyperactivity, fine motor skills, gross motor skills and Tip Toeing. There was a negative correlation between plasma zinc concentration and hyperactivity, and fine motor skills severity.DiscussionThese results suggest an association between plasma Cu/Zn and severity of symptoms associated with autism.

The MitraClip is an US Food and Drug Administration-approved device for inoperable patients with severe degenerative mitral regurgitation (MR) and is under investigation for use in patients with severe functional MR. Simultaneously grasping both leaflets of the mitral valve can be technically challenging, however, in patients with a restricted posterior leaflet. We present one such case in which a pigtail catheter, placed retrograde into the left ventricle, was able to push the ventricular surface of the posterior leaflet into closer approximation with the anterior leaflet, and facilitate successful clip placement. We provide this report in hopes that it will provide a useful strategy for interventionalists faced with this challenging situation.

Cardiac amyloidosis is an under recognized and underdiagnosed heart failure etiology characterized by protein misfolding, myocardial deposition, and restrictive cardiomyopathy. Cardiac involvement in elderly patients most commonly results from the transthyretin protein (ATTR) and carries a poor

Moderate to severe aortic regurgitation (AR) after trans-catheter aortic valve replacement (TAVR) is associated with worse outcomes. The impact of mild AR remains controversial. We evaluated all patients undergoing TF-TAVR at our institution from 2006-2012 (Edwards SAPIEN Valve System, 9000TFX).

One of the key classical pathological features of Alzheimer's disease (AD) is the progressive accumulation of amyloid beta (Aβ42) peptides and their coalescence into highly insoluble senile plaque cores. A major factor driving Aβ42 peptide accumulation is the inability of brain cells to effectively clear excessive amounts of Aβ42 via phagocytosis. The trans-membrane spanning, sensor-receptor known as the "triggering receptor expressed in myeloid cells 2" (TREM2; chr6p21) is essential in the sensing, recognition, phagocytosis and clearance of noxious cellular debris from brain cells, including neurotoxic Aβ42 peptides. Recently, mutations in the TREM2 gene have been associated with amyloidogenesis in neurodegenerative diseases including AD. In this report, we provide evidence that aluminum-sulfate, when incubated with microglial cells, induces the up-regulation of an NF-кB-sensitive micro RNA-34a (miRNA-34a; chr1p36) that is known to target the TREM2 mRNA 3'-untranslated region (3'-UTR), significantly down-regulating TREM2 expression. The aluminum-induced up-regulation of miRNA-34a and down-regulation of TREM2 expression were effectively quenched using the natural phenolic compound and NF-kB inhibitor CAPE [2-phenylethyl-(2E)-3-(3,4-dihydroxyphenyl) acrylate; caffeic-acid phenethyl ester]. These results suggest, for the first time, that an epigenetic mechanism involving an aluminum-triggered, NF-kB-sensitive, miRNA-34a-mediated down-regulation of TREM2 expression may impair phagocytic responses that ultimately contribute to Aβ42 peptide accumulation, aggregation, amyloidogenesis and inflammatory degeneration in the brain.