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The COVID-19 pandemic has presented many stressors for parents. This study was conducted to examine treatment preferences and barriers to care amidst COVID-19. Parents (N ​= ​95) completed self-report measures. Education was provided on interventions (e.g., individual therapy, medication), and acceptability assessed. Elevated stress and distress were observed. Parents indicated interest in services for parenting concerns, stress, anxiety, and depression. Individual therapy and telehealth were highly acceptable, while medication and group therapy were less accepted. Findings highlight the need for specific supports among parents amidst the pandemic. Factors that influence treatment preference warrant further attention. Implications for healthcare service delivery are discussed.

STRUCTURED Abstract: Background: As clinical care and research in adult congenital heart disease (ACHD) increasingly include a focus on quality of life, hearing and reflecting on our patients’ experiences must be a priority. The objective of this study was to describe how living with this chronic illness has affected the adult lives of patients living with ACHD. Methods: We conducted a qualitative study of 25 participants in which we asked about the impact of ACHD on their quality of life. We used thematic analysis to analyze the interview data and identified themes reflecting patients’ reported experiences. Results: Study participants were a mean age of 38 years (range 21–63 years) and reported good functional status. ACHD was characterized as simple (24%), moderate (32%), or complex (44%). Three major themes arose: 1) impact of ACHD on identity, including perception of “normal,” self-esteem, and motivation; 2) sources of emotional distress; and 3) influence on adult decision-making, including careers and relationships. Conclusion: Living with ACHD impacts important aspects related to self-perceived quality of life. Addressing these concerns is important to providing comprehensive, patient-centered ACHD care.

Summary: Traumatic brain injury (TBI) involves complex secondary injury processes following the primary injury. The secondary injury is often associated with rapid metabolic shifts and impaired brain function immediately after the initial tissue damage. Magnetic resonance spectroscopic imaging (MRSI) coupled with hyperpolarization of 13C-labeled substrates provides a unique opportunity to map the metabolic changes in the brain after traumatic injury in real-time without invasive procedures. In this report, we investigated two patients with acute mild TBI (Glasgow coma scale 15) but no anatomical brain injury or hemorrhage. Patients were imaged with hyperpolarized [1-13C]pyruvate MRSI 1 or 6 days after head trauma. Both patients showed significantly reduced bicarbonate (HCO3–) production, and one showed hyperintense lactate production at the injured sites. This study reports the feasibility of imaging altered metabolism using hyperpolarized pyruvate in patients with TBI, demonstrating the translatability and sensitivity of the technology to cerebral metabolic changes after mild TBI.

While 1 to 2% of amyotrophic lateral sclerosis (ALS) is caused by mutations in the SOD1 gene, the basis of the remaining instances of inherited disease is unknown. Neuropathology, mouse modeling, and human genetics have implicated neurofilaments in the pathogenesis of motor neuron diseases such as ALS and Charcot–Marie–Tooth disease (CMT). A systematic analysis of the coding region and intron–exon boundaries of all three neurofilament genes is now reported from DNA samples derived from more than 200 non-SOD1 linked familial and sporadic ALS patients, along with >400 non-disease control individuals. Rare variants within each of the three neurofilament subunits that are predicted to affect neurofilament assembly properties were identified at higher frequency in non-SOD1 mutant ALS samples. However, none could be unambiguously linked to dominantly inherited disease. Thus, mutations in neurofilaments are possible risk factors that may contribute to pathogenesis in ALS in conjunction with one or more additional genetic or environmental factors, but are not significant primary causes of ALS.

Context: Though discrimination in healthcare settings is increasingly recognized, the discriminatory experiences of patients with serious illness has not been well studied., Objectives: Describe racial differences in patient-reported experiences with discrimination in the healthcare setting and examine its association with mistrust., Methods: We used surveys containing patient-reported frequency of discrimination using the Discrimination in Medical Setting (DMS) and Microaggressions in Health Care Settings (MHCS) scales, mistrust using the Group Based Medical Mistrust (GBMM) scale, and patient characteristics including patient-reported race, income, wealth, insurance status, and educational attainment. Univariable and multivariable linear regression models as well as risk ratios were used to examine associations between patient characteristics including self-reported race, and DMS, MHCS, and GBMM scores., Results: In 174 participants with serious illness, racially minoritized patients were more likely to report experiencing discrimination and microaggressions. In adjusted analyses, DMS scores were associated with elements of class and not with race. Black, Native American/Alaskan Native (NA/AN), and multiracial participants had higher MHCS scores compared to White participants with similar levels of income and education. Higher income was associated with lower GBMM scores in participants with similar DMS or MHCS scores, but Black and NA/AN participants still reported higher levels of mistrust., Conclusion: In this cross-sectional study of patients with serious illness, discriminatory experiences were associated with worse mistrust in the medical system, particularly for Black and NA/AN participants. These findings suggest that race-conscious approaches are needed to address discrimination and mistrust in marginalized patients with serious illness and their families., (Copyright © 2024 American Academy of Hospice and Palliative Medicine. All rights reserved.)

Context: Physicians who specialize in pulmonary arterial hypertension (PAH) care for patients facing a serious, life-limiting illness. Palliative care is underutilized in patients with PAH, and little is known about how best to provide palliative care to this patient population., Objectives: Using a qualitative approach, assess physicians' perspectives on barriers and facilitators to the use of palliative care in PAH., Methods: Participants were board-certified pulmonologists and cardiologists recruited from the Pulmonary Hypertension Association's list of physician specialists and academic center websites. We performed one-on-one semi-structured interviews that were recorded, transcribed, and analyzed using thematic analysis., Results: Twelve physicians participated in the study, with a median age of 48.5 years and 20.5 years of clinical experience caring for patients with PAH. We identified the following themes and associated barriers and facilitators to effective implementation of palliative care for patients with PAH: a tailored approach to the individual patient; a PAH-specialist-led culture of care; effective collaboration with palliative care clinicians; and limitations imposed by health systems., Conclusion: PAH physicians are open to palliative care for their patients and are willing to partner with palliative care clinicians to implement this effectively and in the right setting. Areas for targeted improvement in enhancing palliative care for patients with PAH exist, especially enhancing collaboration between PAH physicians and palliative care specialists and navigating barriers in health systems., (Copyright © 2022 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Racial inequities in palliative and end-of-life care have been well-documented for many years. This inequity is long-standing and resistant to many intervention efforts. One reason for this may be that research in racial inequity in palliative care, and the interventions developed, do not account for the effects of race and the everyday racism that patients of color experience while navigating the healthcare system. Public Health Critical Race Praxis (PHCRP) offers researchers new routes of inquiry to broaden the scope of research priorities in palliative care and improving racial outcomes through a novel conceptual framework and methodology. PHCRP, based off critical race theory (CRT), contains 10 principles within four foci to guide researchers toward a more race conscious approach for the generation of research questions, research processes, and development of interventions targeting racial inequities., (Copyright © 2021 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Psychosocial and supportive care interventions are a cornerstone of palliative care science, yet there is little published guidance regarding how to develop, test, adapt, and ultimately disseminate evidence-based interventions. Our objective was to describe the application of a single intervention-development model in multiple populations of patients with serious illness. Specifically, we use the "Promoting Resilience in Stress Management" (PRISM) intervention as an exemplar for how the Obesity Related Behavioral Intervention Trials (ORBIT) intervention-development model may be applied to: 1) create an initial palliative care intervention; 2) adapt an existing intervention for a new patient-population; 3) expand an existing intervention to include new content; and, 4) consider dissemination and implementation of a research-proven intervention. We began by identifying key psychological and social science theories and translating them a testable clinical hypothesis. Next, we conducted observational studies and randomized trials to design, refine, and standardize PRISM within unique patient-populations. We moved backwards in the ORBIT model when necessary to adapt or expand PRISM content and delivery-strategies to meet patient-reported needs. Finally, we began to explore PRISM's effectiveness using Dissemination and Implementation research methods. Key lessons include the need to ground intervention-development in evidence-based theory; involve patient, clinician, and other stakeholders at every phase of development; "meet patients where they are at" with flexible delivery strategies; invest in the time to find the right scientific premise and the right intervention content; and, perhaps most importantly, involve an interdisciplinary research team., (Copyright © 2021 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

The COVID-19 pandemic strained health-care systems throughout the world. For some, available medical resources could not meet the increased demand and rationing was ultimately required. Hospitals and governments often sought to establish triage committees to assist with allocation decisions. However, for institutions operating under crisis standards of care (during times when standards of care must be substantially lowered in the setting of crisis), relying on these committees for rationing decisions was impractical-circumstances were changing too rapidly, occurring in too many diverse locations within hospitals, and the available information for decision making was notably scarce. Furthermore, a utilitarian approach to decision making based on an analysis of outcomes is problematic due to uncertainty regarding outcomes of different therapeutic options. We propose that triage committees could be involved in providing policies and guidance for clinicians to help ensure equity in the application of rationing under crisis standards of care. An approach guided by egalitarian principles, integrated with utilitarian principles, can support physicians at the bedside when they must ration scarce resources., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The choice of antithrombotic therapy for atrial fibrillation (AF) patients who have an acute coronary syndrome (ACS) or have undergone percutaneous coronary intervention (PCI) is challenging. We aimed to assess outcomes between dual-antithrombotic therapy with the use of direct-acting oral anticoagulants (DOACs) plus an antiplatelet agent (dual therapy) compared with warfarin plus 2 antiplatelet agents (triple therapy) for AF patients after PCI or with ACS., Methods: Systematic searches of multiple major databases were performed from their inception through September 2019. We included only randomized controlled trials. Odds ratios (ORs) were pooled with the use of a random-effects model., Results: We identified 4 randomized controlled trials, which included 7168 patients. Compared with triple-antithrombotic therapy with warfarin, dual-antithrombotic therapy with DOACs was associated with a significant reduction in major bleeding (OR 0.56, 95% confidence interval [CI] 0.38-0.82; P = 0.003) as well as major bleeding or clinically relevant nonmajor bleeding (OR 0.53, 95% CI 0.38-0.75; P < 0.001). The rate of composite of death and ischemic events (stroke and myocardial infarction) was not statistically different between groups (OR 1.21, 95% CI 0.99-1.49; P = 0.06). There was no significant difference between groups in the rate of death (OR 1.20, 95% CI 0.95-1.53; P = 0.13)., Conclusions: In patients with AF and recent ACS or PCI, the use of dual-antithrombotic therapy with DOACs was associated with less major bleeding and less major bleeding or clinically relevant nonmajor bleeding compared with triple therapy. The use of dual therapy also showed nonsignificantly higher composite of death and ischemic events but no difference in mortality., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Anti-platelet therapy is commonly used in patients receiving oral anticoagulation and may increase bleeding risk among patients undergoing cardiac implantable electronic device (CIED) surgery. We sought to determine the proportion of anticoagulated patients who are concomitantly receiving anti-platelet therapy, the associated risk of clinically significant hematoma (CSH), and the proportion of patients in whom anti-platelet usage is guideline-indicated., Methods: A secondary analysis of the Bridge or Continue Coumadin for Device Surgery Randomized Controlled Trial (BRUISE CONTROL). Patients who were receiving warfarin, had an annual predicted risk of thromboembolism of ≥5% and were scheduled to undergo non-emergent CIED surgery were randomized to continued warfarin versus heparin bridging. In the current analysis, patients were divided into those receiving anti-platelet therapy and those not receiving anti-platelet therapy. The incidence of CSH was compared in both groups. The proportion of patients on potentially inappropriate and potentially interruptible antiplatelet therapy was estimated., Results: All 681 patients enrolled in BRUISE CONTROL were included, of whom 280 received and 401 did not receive anti-platelet therapy. Anti-platelet therapy increased the risk of CSH (relative risk, 1.72; 95% confidence interval (CI), 1.09 to 2.72; P = 0.02). Of the 280 patients receiving anti-platelet therapy, 97 (34.6%) had no guideline indication for concomitant anti-platelet therapy and an additional 146 (52.1%) were on anti-platelet therapy that could potentially have been interrupted around CIED surgery., Conclusions: Concomitant anti-platelet therapy in patients receiving anticoagulation is associated with a significant risk of CSH. The majority of concomitant anti-platelet therapy is potentially inappropriate or interruptible., Trial Registration: clinicaltrials.gov Identifier: (NCT00800137)., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: Factors that influence decision of non-vitamin K antagonist oral anticoagulants (NOACs) use among older atrial fibrillation (AF) patients in long-term care (LTC) facilities have not been well studied. The aim of this study was to assess whether increased frailty influenced physicians to prescribe NOACs over warfarin., Design: We retrospectively reviewed the electronic medical record (EMR) and pharmacy data of 25 LTC facilities in Ontario, Canada, in May 2015. The diagnosis of AF was ascertained from EMR and confirmed by complete chart review of a random sample of the cohort. A score of ≥2 on the Changes in Health, End-stage disease, Signs, and Symptoms (CHESS) scale was used as a surrogate marker of frailty., Measures: Multivariable logistic regression model was used to assess whether a higher frailty score is associated with the use of NOACs in comparison to warfarin, independent of potential patient-level confounders., Setting and Participants: In total, 3378 active residents were assessed in 25 LTC facilities. All the residents were ≥65 years old. We identified 433 residents with AF; 273 (63%) AF residents were on anticoagulation therapy and included in the analysis., Results: Residents were more often treated with NOACs (n = 159; 58%) in comparison to warfarin (n = 114; 42%). A CHESS score of ≥2 increased the odds of prescribing NOACs by 2.46 times [95% confidence interval (CI) 1.11, 5.49; P = .03] when adjusted for important patient-level factors. Patients with hypertension had a trend of increased NOAC prescriptions but did not reach statistical significance [odds ratio 2.1 (95% CI 0.91, 4.81), P = .08]. None of the patient-level factors were associated with NOAC prescriptions., Conclusions and Implications: In this real world cohort of AF patients in LTC who are prescribed an oral anticoagulation therapy, a higher CHESS score (≥2) is associated with increased use of NOACs in comparison to warfarin., (Copyright © 2019 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Cardiac implantable electrical devices (CIEDs) are subject to advisories and complications that can result in morbidity and mortality for patients; there is currently no system in Canada to track these., Methods: This was a multicenter, prospective cohort study conducted at 5 centers to determine feasibility. Patients with a de novo high-voltage (HV) lead implantation were included and followed for a minimum of 1 year., Results: There were 611 leads enrolled into the registry over 18 months. The mean age was 62.4 ± 12.8 years; 144 (23.6%) women were enrolled. The indication for lead implantation was for primary prevention in 65.5%. There were 497 (82.1%) de novo devices (single chamber: 54.5%, dual chamber: 20.5%, cardiac resynchronization therapy [CRT] 25.0%); the remainder of the procedures was a system revision for either upgrade (8.1%) or lead revision (9.8%). The lead revision rate at 1 year was 3.4%, with the primary reason being lead dislodgements. Mortality rate was 3.8% at 1 year. The rate of any device-related complication was 2.0% at 30 days, with the highest rate in CRT implants (4.9%, P = 0.0105). At 1 year, the complication rate was 4.5%, with no significant difference among device types., Conclusions: This study demonstrates that device surveillance is feasible and highlights (1) the need for CIED surveillance to track device-related complications, (2) the scope of this should be larger, and (3) mandatory participation should be considered. This system could predict CIEDs that may be susceptible to higher than usual rates of failure, mitigating adverse outcomes in patients., (Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Alzheimer's disease (AD) is an age-related neurodegenerative disorder. Although an accumulation of brain amyloid-β (Aβ) peptide and hyperphosphorylated tau protein have been implicated in the pathogenesis of AD, the etiology of the disease remains unclear. Mitochondrial dysfunction has been identified as an early event in AD pathogenesis and is reflected by reduced metabolism, disruption of Ca 2+ homeostasis, and increased levels of reactive oxygen species, lipid peroxidation, and apoptosis. The focus of this review is the involvement of mitochondrial dysfunction in AD, and specifically, the role of the voltage-dependent anion channel 1 (VDAC1), which has been linked to AD pathogenesis. VDAC1 is a multi-functional protein, expressed in the mitochondria and other cell compartments, including the plasma membrane. The protein regulates the main metabolic and energetic functions of the cell, including Ca 2+ homeostasis, oxidative stress, and mitochondria-mediated apoptosis. VDAC1 represents a hub protein that interacts with over 150 other proteins including phosphorylated tau, Aβ, and γ-secretase, and participates in their toxicity. The high levels of VDAC1 demonstrated post-mortem in the brains of AD patients and in amyloid precursor protein (APP) transgenic mice prompted the hypothesis that the protein may be associated with neuronal cell destruction since over-expression of VDAC1 triggers cell death. Thus, targeting mitochondrial dysfunction via VDAC1, to prevent this pro-apoptotic activity, could represent a novel strategy for inhibiting cell death. In addition, the review also discusses possible VDAC1 involvement in the link between AD and diabetes and the inverse association between cancer and AD., (Copyright © 2018. Published by Elsevier Ltd.)

Background: The Riata lead advisory was announced in 2011 and has posed unique management challenges because of cable externalization and insulation abrasion, in some cases leading to sudden loss of defibrillation., Objective: The purpose of this study was to provide further data on the rate of electrical failure in a population of patients with a Riata lead under advisory., Methods: Using the Canadian Registry of Electronic Device Outcomes, prospective follow-up data were collected on 1352 Riata leads under advisory in 17 implantable cardioverter-defibrillator (ICD) implantation centers in Canada. Data on electrical and structural failure were collected, as well as periprocedural complications related to lead revision (abandonment or extraction)., Results: Of the 1352 leads included in this 12-month follow-up cohort, 110 leads were revised. Mean follow-up time was 10.4 ± 1.5 years. The 12-year rate of electrical failure for the 8Fr lead was 9.45%, whereas the 10-year failure rate for the 7Fr lead was 7.25% and was not found to be accelerating. Of the leads revised because of advisory only (patient preference, advisory related, electrical or structural failure), the majority were abandoned (n = 54 [76.0%]), whereas 17 (24.0%) were extracted using power tools. The rate of major complications in each group was 5.6% and 5.9%, respectively., Conclusion: This report provides further data on the risk of electrical lead failure over a long lead dwell time. The risk of failure exceeds the risk of periprocedural major complications, indicating that the risk-to-benefit ratio is favorable to revise the lead in appropriate clinical scenarios., (Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Because cardiovascular implantable electronic devices are increasingly indicated in older patients, and the burden of cancer is rising with the growth and aging of the world population, the management of patients with cardiac devices who require radiotherapy for cancer treatment is a timely concern. Device malfunctions might occur in as high as 3% of radiotherapy courses, posing a substantial issue in clinical practice. A nonsystematic comprehensive review was undertaken. We searched PubMed and the MEDLINE database for randomized controlled trials, meta-analyses, systematic reviews, observational studies, in vitro/in vivo studies, and case reports. Articles were selected by 2 independent reviewers, and emphasis was given to information of interest to a general medical readership. The pathophysiology and predictors of cardiovascular implantable electronic device malfunction due to radiotherapy are reviewed, recommendations for the management of patients with such devices undergoing radiotherapy are summarized, and the clinical significance and future directions of this field are discussed. Radiotherapy-induced device malfunctions are rare, but because of the potential complications, the development of evidence-based guidelines for the management of patients with cardiovascular implantable electronic devices undergoing radiotherapy is a timely concern., (Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Progressive fibrotic interstitial lung diseases (ILDs) are characterised by major reductions in quality of life and survival and have similarities to certain malignancies. However, palliative care expertise is conspicuously inaccessible to many patients with ILD. Unmet patient and caregiver needs include effective pharmacological and psychosocial interventions to improve quality of life throughout the disease course, sensitive advanced care planning, and timely patient-centred end-of-life care. The incorrect perception that palliative care is synonymous with end-of-life care, with no role earlier in the course of ILD, has created a culture of neglect. Interventions that aim to improve life expectancy are often prioritised without rigorous assessment of the individual's health and psychosocial needs, thereby inadvertently reducing quality of life. As in malignant disorders, radical interventions to slow disease progression and palliative measures to improve quality of life should both be prioritised. Efficient patient-centred models of palliative care must be validated, taking into account religious and cultural differences, as well as variability of resources. Effective implementation of palliative care for ILD will require multidisciplinary participation from clinicians, specialist nurses, psychologists, social workers, and, in some countries, non-governmental faith and community-based organisations with access to palliative care expertise., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The vertebrate brain arises from the complex organization of millions of neurons. Neurogenesis encompasses not only cell fate specification from neural stem cells, but also the terminal molecular and morphological maturation of neurons at correct positions within the brain. RE1-silencing transcription factor (Rest) is expressed in non-neural tissues and neuronal progenitors where it inhibits the terminal maturation of neurons by repressing hundreds of neuron-specific genes. Here we show that Rest repression of maturation is intimately linked with the migratory capability of zebrafish facial branchiomotor neurons (FBMNs), which undergo a characteristic tangential migration from hindbrain rhombomere (r) 4 to r6/r7 during development. We establish that FBMN migration is increasingly disrupted as Rest is depleted in zebrafish rest mutant embryos, such that around two-thirds of FBMNs fail to complete migration in mutants depleted of both maternal and zygotic Rest. Although Rest is broadly expressed, we show that de-repression or activation of Rest target genes only within FBMNs is sufficient to disrupt their migration. We demonstrate that this migration defect is due to precocious maturation of FBMNs, based on both morphological and molecular criteria. We further show that the Rest target gene and alternative splicing factor srrm4 is a key downstream regulator of maturation; Srrm4 knockdown partially restores the ability of FBMNs to migrate in rest mutants while preventing their precocious morphological maturation. Rest must localize to the nucleus to repress its targets, and its subcellular localization is highly regulated: we show that targeting Rest specifically to FBMN nuclei rescues FBMN migration in Rest-deficient embryos. We conclude that Rest functions in FBMN nuclei to inhibit maturation until the neurons complete their migration., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The majority of patients receiving implantable cardioverter-defibrillator (ICD) implantation under current guidelines never develop sustained ventricular arrhythmia; therefore, better markers of risk for sustained ventricular tachycardia and/or ventricular fibrillation are needed., Objective: The purpose of this study was to identify cardiac magnetic resonance arrhythmic risk predictors of ischemic cardiomyopathy before ICD implantation., Methods: Forty-three subjects (mean age, 64.5 ± 11.9 years) with previous myocardial infarction who were referred for ICD implantation were evaluated by cardiac magnetic resonance imaging (MRI). The MRI protocol included left ventricular functional parameter assessment using steady-state free precession and late gadolinium enhancement MRI using inversion recovery fast gradient echo. Left ventricular functional parameters were measured using cardiac magnetic resonance software. Subjects were followed up for 6-46 months, and the events of appropriate ICD treatments (shocks and antitachycardia pacing) were recorded., Results: Twenty-eight patients experienced 46 spontaneous episodes during a median follow-up duration of 30 months. The total myocardial infarct (MI) size (18.05 ± 11.44 g vs 38.83 ± 19.87 g; P = .0006), MI core (11.63 ± 7.14 g vs 24.12 ± 12.73 g; P = .0002), and infarct gray zone (6.43 ± 4.64 g vs 14.71 ± 7.65 g; P = .0004) were significantly larger in subjects who received appropriate ICD therapy than in those who did not experience an episode of ventricular tachycardia and/or ventricular fibrillation. Multivariate regression analyses for the infarct gray zone and MI core adjusted for New York Heart Association class, diabetes, and etiology (primary or secondary prevention) revealed that the gray zone and MI core were predictors of appropriate ICD therapies (P = .0018 and P = .007, respectively)., Conclusion: The extent of MI scar may predict which patients would benefit most from ICD implantation., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The data supporting the practice of empiric slow pathway ablation (ESPA) in patients with documented supraventricular tachycardia (SVT) who are non-inducible at electrophysiology study (EPS) is limited. The aim of this study is to assess the efficacy of ESPA in adults., Methods: A multi-center cohort study of patients who had ESPA between January 2008 and October 2013 was performed. Patients were identified by screening sequential SVT ablation procedures., Results: Forty-three (5%) out of 859 SVT ablation procedures were identified as ESPA. The median age was 53 (IQR: 24) years; 63% were female. All patients had pre-EPS documentation of SVT (either strip or ECG). In 23 (53.5%) cases, pre-EPS ECG showed short RP tachycardia. Thirty-two (74.4%) patients had dual atrioventricular nodal physiology (DAVNP) plus echo beats. Junctional rhythm (JR) as procedural endpoint was noted in 39 (90.7%) patients. In 18 (41.9%) patients, the abolishment of DAVNP was achieved. No complications were encountered. A median follow-up of 17 months (range: 6 to 31 months) revealed 83.7% (36 of 43) success rate, defined as the absence of pre-procedural symptoms and any documented sustained arrhythmia. As compared to patients with recurrence (n=7), patients with no recurrence (n=36) had significantly higher prevalence of clinical short RP tachycardia (61.1% vs. 14.3%, p=0.038), and EPS finding of DAVNP plus echo beats (80.6% vs. 42.9%, p=0.034)., Conclusions: ESPA is a reasonable approach in patients with documented SVT, in particular in short RP tachycardia, who are not inducible at EPS. Larger studies are required to assess this practice., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Dual-chamber (DDD) and VDD pacing are recognized alternatives for patients with advanced atrioventricular (AV) conduction abnormalities and spared sinus node function. The comparative data between these 2 modes are limited., Methods: A literature search was performed using multiple major databases. Outcomes of interest were (1) adverse events including incidence of atrial fibrillation (AF) and (2) procedural parameters. Odds ratio (OR) was reported for dichotomous variables and standardized mean difference (SMD) for continuous variables., Results: Eight controlled studies (7 cohorts and 1 randomized controlled trial: total 1942 patients) were included. VDD mode was used in 922 patients. Mean follow-up period for the VDD group was 51 ± 24 months. There was a trend toward lower overall adverse events in the VDD group (9.6% vs 11.6%; OR, 0.74 [95% confidence interval (CI), 0.51-1.05; P = 0.09]). Shorter implantation and fluoroscopy times were noted with VDD pacing (46.2 ± 12 vs 65.9 ± 20 minutes; SMD, -0.96 [95% CI, -1.26 to -0.66; P < 0.0001] and 4.6 ± 1 vs 9.3 ± 0.4 minutes; SMD, -0.83 [95% CI, -1.38 to -0.29; P = 0.003], respectively). Mean P-wave amplitude was significantly lower in VDD (1.5 ± 0.8 mV vs 3.1 ± 0.9 mV; P = 0.02). The incidence of AF was lower in the VDD group but it did not reach statistical significance (7.5% vs 13.0%; OR, 0.7; 95% CI, 0.39-1.27; P = 0.24)., Conclusions: This meta-analysis suggests that VDD is a reasonable alternative to DDD pacemakers with lower pneumothorax risk and shorter implantation and fluoroscopy times. More high-quality data are required to definitively compare the 2 strategies., (Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Anthrax lethal factor (LF) is a zinc-dependent metalloendopeptidase and a member of the gluzincin family. The current report demonstrates a high metal substitution tolerance of LF atypical of gluzincins and other zinc-dependent metalloproteases. Mn(2+), Co(2+), Ni(2+), Cu(2+) and Cd(2+) were found to reactivate the apoprotein of LF to a level either comparable to or significantly higher than that noted for the native zinc enzyme. The most active form of LF was obtained with Cu(2+), a surprising observation since most Cu(2+)-substituted zinc proteases display very low activity. Cu(2+)-substituted LF (CuLF), prepared by direct exchange and by apoprotein reconstitution methodologies, displayed a several-fold higher catalytic competence towards chromogenic and fluorogenic LF substrates than native LF. CuLF bound Cu(2+) tightly with a dissociation constant in the femtomolar range. The electron paramagnetic resonance spectrum of CuLF revealed the protein-bound metal ion to be coordinated to two nitrogen donor atoms, suggesting that Cu(2+) binds to both active site histidine residues. While ZnLF and CuLF (prepared by direct exchange) were capable of killing RAW 264.7 murine macrophage-like cells, apoLF and all metal-reconstituted apoprotein preparations failed to elicit a cytotoxic response. Competition experiments using apoLF/ZnLF mixtures demonstrated the propensity of apoLF to relieve ZnLF-induced cell death, suggesting that both protein forms can compete with each other for binding to protective antigen. The lack of cytotoxicity of apoLF and its metal-reconstituted variants likely originates from structural perturbations in these proteins which might prevent their translocation into the cytoplasm., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Substantial numbers of deaths occur among implantable cardioverter defibrillator (ICD) recipients. Timely follow-up after ICD implantation might improve patient outcomes. Our objective was to examine follow-up care and outcomes among patients undergoing ICD implantation., Methods: We compared patient characteristics and outcomes of those with late (> 12 weeks) vs early defibrillator clinic follow-up after ICD implantation in the Ontario ICD Database from 2007 to 2011. We examined the effect of ICD clinic follow-up visits after implant compared with primary care physician tracer on mortality outcomes using time-varying covariate analyses., Results: Among 8096 ICD recipients (age 64.6 ± 12.6 years), 1145 (14%) received delayed follow-up. Patients with early ICD clinic follow-up experienced reduced risk of all-cause mortality, with a hazard ratio [HR] of 0.69 (95% confidence interval [CI], 0.50-0.95; P = 0.023) adjusted for clinical factors, primary care visits after discharge, and distance to follow-up centre. Early ICD clinic follow-up was associated with a reduction in out-of-hospital death with adjusted HR of 0.52 (95% CI, 0.36-0.76; P = 0.001) but not with a significant change in cardiovascular hospitalizations. In a tracer analysis, early primary care physician follow-up was associated with a nonsignificant trend toward increased mortality with an adjusted HR of 1.48 (95% CI, 0.97-2.25; P = 0.072). Reduced estimated glomerular filtration rate, secondary prevention or replacement devices, myocardial ischemia, smoking, and greater geographic distance to the implanting centre increased the odds of delayed follow-up., Conclusions: After device implantation, early defibrillator clinic follow-up was associated with reduced risk of all-cause and out-of-hospital death compared with those experiencing delayed follow-up., (Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Conflicting data exist regarding the association between left ventricular (LV) lead position and benefit from cardiac resynchronization therapy. We evaluated the relationships between LV lead positions and the risk of death or hospitalization for heart failure (HF) in the cardiac resynchronization therapy arm of the Resynchronization-Defibrillation for Ambulatory Heart Failure Trial (RAFT)., Methods: LV lead position was categorized by site investigator (MD) and in a chest radiograph core laboratory (CXR) as "anterior," "lateral," or "posterior" in the short axis, and "basal," "mid," or "apical" in the long axis. Agreement between MD and CXR LV lead position classification was evaluated and the independent relationship between LV lead position and clinical outcome was assessed using Cox multivariable models., Results: Agreement between MD and CXR LV lead position was poor (κ ≤ 0.26). Over 39 ± 20 months, 140 of 447 (31.3%) patients met the RAFT primary end point (death or HF hospitalization). In adjusted analyses, neither MD-determined nor CXR-determined anterior or apical LV lead position was significantly associated with the primary outcome. However, CXR-defined apical LV lead position was associated with a higher risk of HF hospitalization (hazard ratio, 1.99; P = 0.004)., Conclusions: Poor agreement between implanting physician and core lab CXR-based categorizations of LV lead position was observed. Neither categorization method resulted in significant associations between apical or anterior LV lead position and the risk of the composite primary outcome of death or heart failure hospitalization. However, CXR-defined apical lead position was associated with increased risk of HF hospitalization., (Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Robotic systems are becoming increasingly common in complex ablation procedures. We conducted systematic review and meta-analysis on the procedural outcomes of Magnetic Navigation System (MNS) in comparison to conventional catheter navigation for atrial fibrillation (AF) ablation., Methods: An electronic search was performed using multiple databases between 2002 & 2012. Outcomes were: acute and long-term success, complications, total procedure, ablation and fluoroscopic times., Results: Fifteen studies (11 nonrandomized controlled studies & 4 case series) involving 1647 adult patients were identified. In comparison between MNS and conventional groups, a tendency towards higher acute success was noted with conventional group but with similar long-term freedom from AF (95% vs. 97%, odds ratio (OR) 0.25 (95% confidence interval [CI] 0.06; 1.04, p=0.057); 73% vs. 75%, OR 0.92 (95% CI 0.69; 1.24, p=0.59), respectively). A significantly shorter fluoroscopic time was achieved with MNS (57 vs. 86 min, standardized difference in means (SDM) -0.90 (95% CI -1.68; -0.12, p=0.024)). Longer total procedure and ablation times were noted with MNS (286 vs. 228 min, SDM 0.7 (95% CI 0.28; 1.12, p=0.001); 67 vs. 47 min, SDM 0.79 (95% CI 0.18; 1.4, p=0.012), respectively). Overall complication rate was similar (2% vs. 5%, OR 0.48 (95% CI 0.18; 1.26, p=0.135)), however rate of significant pericardial complication defined either as tamponade or effusion requiring intervention/hospitalization was significantly lower in MNS (0.3% vs. 2.5%, p=0.005)., Conclusions: Our results suggest that MNS has similar rates of success and possibly superior safety outcomes when compared to conventional manual catheter ablation for AF., (© 2013.)

Background: The safety and efficacy of dabigatran in the periprocedural period for patients undergoing atrial fibrillation ablation is not well established. We conducted a meta-analysis of the periprocedural use of dabigatran vs warfarin (with or without heparin bridging)., Methods: A literature search was performed using multiple databases. Outcomes were (1) major bleeding; (2) minor bleeding; and (3) thromboembolic events. Odds ratios (ORs) were reported for dichotomous variables., Results: Eleven controlled studies (9 cohorts, 1 randomized controlled trial and 1 case-control study; 3841 patients) were identified. Dabigatran was used in 1463 patients, uninterrupted in 223 and held up to 36 hours in the remainder. No significant differences were noted in major bleeding rates between dabigatran and warfarin groups (1.9% vs. 1.6%; OR, 1.04 [95% confidence interval (CI), 0.51-2.13]; P = 0.92). Cardiac tamponade was observed in 1.4% in dabigatran vs 1.1% in warfarin groups (OR, 1.1; 95% CI, 0.55-2.11; P = 0.82). Similar rates for dabigatran vs. warfarin were reported for minor bleeding (3.8% vs. 4.5%; OR, 0.85; 95% CI, 0.58-1.25; P = 0.40), hematoma (2% vs. 2.7%; OR, 0.67; 95% CI, 0.41-1.08; P = 0.1), and thromboembolic events (0.6% vs. 0.1%; OR, 2.51; 95% CI, 0.78-8.11; P = 0.12)., Conclusions: This meta-analysis suggests that dabigatran and warfarin have similar safety and efficacy overall for periprocedural anticoagulation in patients undergoing radiofrequency atrial fibrillation ablation. Signals were seen favouring dabigatran (for hematomas) and warfarin (for thromboembolic events), but neither was statistically significant because of low event rates. More high-quality data are required to definitively compare the 2 strategies., (Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: The St. Jude Medical Riata family of implantable cardioverter-defibrillator (ICD) leads has demonstrated a high rate of externalized conductors and electrical failure., Objective: Given similar design elements of Durata to Riata, the purpose of this study was to assess the rates of failure of the Riata ST Optim and Durata lead families in Canada., Methods: All Canadian ICD-implanting centers were invited to submit follow-up information on all Optim-coated ICD leads implanted. Electrical failure was defined as a rapid change in impedance or pacing capture threshold leading to lead revision, or oversensing due to noise. Externalized conductors were defined as appearance of conductor wires outside the lead body. Systematic fluoroscopic screening for externalized conductors was not performed., Results: As of December 1, 2012, 15 of 25 centers provided data on 3981 leads (44% of those sold in Canada during the same timeframe): 3477 Durata and 504 Riata ST Optim leads. The most common model numbers were 7122 (1516 leads [38%]), 7121 (707 leads [18%]), and 7120 (622 leads [16%]). Mean follow-up duration from implant to December 1, 2012, was 4.47 ± 0.48 years for Riata ST Optim leads and 2.00 ± 1.10 years for Durata leads. The annual rate of lead failure was 0.27% per year for Riata ST Optim leads and 0.24% per year for Durata leads. No instances of externalized conductors were identified in the failed leads. No deaths were attributed to lead failure; however, 2 patients experienced inappropriate shocks due to lead failure., Conclusion: The overall electrical failure rates of the Riata ST Optim and Durata leads appear to be low, and no instances of externalized conductors were observed., (© 2013 Heart Rhythm Society. All rights reserved.)

Two virtually identical acireductone dioxygenases, ARD and ARD', catalyze completely different oxidation reactions of the same substrate, 1,2-dihydroxy-3-keto-5-(methylthio)pentene, depending exclusively on the nature of the bound metal. Fe(2+)-dependent ARD' produces the α-keto acid precursor of methionine and formate and allows for the recycling of methionine in cells. Ni(2+)-dependent ARD instead produces methylthiopropionate, CO, and formate, and exits the methionine salvage cycle. This mechanistic difference has not been understood to date but has been speculated to be due to the difference in coordination of the substrate to Fe(2+)versus Ni(2+): forming a five-membered ring versus a six-membered ring, respectively, thus exposing different carbon atoms for the attack by O2. Here, using mixed quantum-classical molecular dynamics simulations followed by the density functional theory mechanistic investigation, we show that, contrary to the old hypothesis, both metals preferentially bind the substrate as a six-membered ring, exposing the exact same sites to the attack by O2. It is the electronic properties of the metals that are then responsible for the system following different reaction paths, to yield the respective products. We fully explain the puzzling metal-induced difference in functionality between ARD and ARD' and, in particular, propose a new mechanism for ARD'. All results are in agreement with available isotopic substitution and other experimental data., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: A unique form of lead failure has been described in the Riata (8-F) and Riata ST (7-F) silicone defibrillation lead degradation of the outer insulation, resulting in the externalization of conductor cables., Objective: To assess rates of lead revision due to lead failure in Riata leads affected by the Riata advisory., Methods: Nineteen implantable cardioverter-defibrillator implant and follow-up centers were surveyed., Results: As of March 1, 2012, there were 5043 known affected leads implanted in Canada. Data on 4358 (86.4%) leads were obtained; 65.3% of these were Riata (8-F) and 32.4% were Riata ST (7-F) leads. The median time from implant to last follow-up was 5 years. Electrical abnormalities were reported in 4.6% of the affected leads; 8.0% of these were found to have concomitant radiographic evidence of externalization. The rate of electrical failure was higher in the 8-F (5.2%) vs 7-F (3.3%) leads (P = .007). Oversensing with or without inappropriate shocks was reported in 39.8% of the leads with confirmed failure. Abnormally high or low impedance values (29.9%) and elevated pacing capture thresholds (43.8%) were frequently reported. One death (0.5%) attributed to lead failure was reported. Among the leads that were replaced, 21% were extracted. Two major complications (1.0%) were attributed to extraction of these leads., Conclusions: The overall rate of lead failure in the Riata (8-F) and Riata ST (7-F) leads is higher than previously reported by using passive surveillance data. The impact of recent advisories related to these leads is not yet apparent., (Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Anticoagulation in patients undergoing atrial fibrillation (AF) ablation is crucial to minimize the risk of thromboembolic complications. There are broad ranges of approaches to anticoagulation management pre and post AF ablation procedures. The purpose of this study was to determine the anticoagulation strategies currently in use in patients peri- and post AF ablation in Canada., Methods: A Web-based national survey of electrophysiologists performing AF ablation in Canada collected data regarding anticoagulation practice prior to ablation, periprocedural bridging, and duration of postablation anticoagulation., Results: The survey was completed by 36 (97%) of the 37 electrophysiologists performing AF ablation across Canada. Prior to AF ablation, 58% of electrophysiologists started anticoagulation for patients with paroxysmal AF CHADS(2) scores of 0 to 1, 92% for paroxysmal AF CHADS(2) scores ≥ 2, 83% for persistent AF CHADS(2) scores of 0 to 1, and 97% for persistent AF CHADS(2) scores ≥ 2. For patients with CHADS(2) 0 to 1, warfarin was continued for at least 3 months by most physicians (89% for paroxysmal and 94% for persistent AF). For patients with CHADS(2) ≥ 2 and with no recurrence of AF at 1 year post ablation, 89% of physicians continued warfarin., Conclusions: Although guidelines recommend long-term anticoagulation in patients with CHADS(2) ≥ 2, 11% of physicians would discontinue warfarin in patients with no evidence of recurrent AF 1 year post successful ablation. Significant heterogeneity exists regarding periprocedural anticoagulation management in clinical practice. Clinical trial evidence is required to guide optimal periprocedural anticoagulation and therapeutic decisions regarding long-term anticoagulation after an apparently successful catheter ablation for AF., (Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Pacemakers can automatically identify and catalog atrial high-rate episodes (AHREs). While most AHREs represent true atrial tachyarrhythmia/atrial fibrillation (AT/AF), a review of stored electrograms suggests that a substantial proportion do not. As AHREs may lead to the initiation of oral anticoagulation, it is crucial to understand the relationship between AHREs and true AT/AF., Objective: To compare the positive predictive value of AHREs for electrogram-confirmed AT/AF for various atrial rates and episode durations., Methods: By using data from 2580 patients who participated in the ASymptomatic atrial fibrillation and Stroke Evaluation in pacemaker patients and the AF Reduction atrial pacing Trial, all AHREs >6 minutes and >190 beats/min with available electrograms were reviewed to determine whether they represented true AT/AF. The positive predictive value of these AHREs was assessed for episode durations of 6 minutes, 30 minutes, 6 hours, and 24 hours at atrial rates of 190 and 250 beats/min., Results: Of 5769 AHREs >6 minutes and >190 beats/min, 82.7% were true AT/AF and 17.3% were false positives (predominantly due to repetitive non-re-entrant ventriculoatrial synchrony). False positives dropped to 6.8%, 3.3%, and 1.8% when the threshold duration was increased to 30 minutes, 6 hours, and 24 hours, respectively. Increasing the threshold heart rate to 250 beats/min added little to the positive predictive value when longer threshold durations were used., Conclusions: By using a cutoff of >6 minutes and >190 beats/min, the rate of false-positive AHREs is 17.3%, making physician review of electrograms essential. For AHREs lasting >6 hours, the rate of false positives is 3.3%, making physician review less crucial., (Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Following recent cases of nonphysiologic noise noted early after defibrillator implantation, the Canadian Heart Rhythm Society Device Committee decided to evaluate the implications of this problem., Objective: To determine the incidence and consequences of nonphysiologic noise early after defibrillator implantation., Methods: The Canadian Heart Rhythm Society Device Committee surveyed all Canadian defibrillator implanting centers regarding their implant volumes and number of cases where nonphysiologic noise had been noted early (< 24 hours) after implant over the preceding 2 years. For such cases, information regarding the manufacturer and occurrence of inappropriate shock or inhibition of pacing was reported., Results: Responses were obtained from 20 of 23 surveyed implanting centers, with a total implant volume of 4960 defibrillators per year. The occurrence of nonphysiologic noise early after implantation was noted in 25 cases over the preceding 2 years (0.25%). Noise was detected in devices of all 3 of the leading volume device manufacturers. There were 2 cases of inappropriate shocks and 2 cases of symptomatic pacing inhibition. In 4 cases, removal of the lead from the header and retesting with the analyzer confirmed normal lead function. In all cases, the noise resolved within 24 hours., Conclusion: Nonphysiologic noise early after defibrillator implantation was noted in 0.25% of procedures and was not limited to one specific manufacturer. This noise may result in an inappropriate shock or inhibition of pacing in a pacemaker-dependent patient. This transient phenomenon, possibly related to fluid and/or air in the header, appears to always resolve without surgical intervention., (Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Anthrax lethal factor (LF) is a zinc-dependent endopeptidase involved in the cleavage of mitogen-activated protein kinase kinases near their N-termini. The current report concerns the preparation of cobalt-substituted LF (CoLF) and its characterization by electronic spectroscopy. Two strategies to produce CoLF were explored, including (i) a bio-assimilation approach involving the cultivation of LF-expressing Bacillus megaterium cells in the presence of CoCl(2), and (ii) direct exchange by treatment of zinc-LF with CoCl(2). Independent of the method employed, the protein was found to contain one Co(2+) per LF molecule, and was shown to be twice as active as its native zinc counterpart. The electronic spectrum of CoLF suggests the Co(2+) ion to be five-coordinate, an observation similar to that reported for other Co(2+)-substituted gluzincins, but distinct from that documented for the crystal structure of native LF. Furthermore, spectroscopic studies following the exposure of CoLF to thioglycolic acid (TGA) revealed a sequential mechanism of metal removal from LF, which likely involves the formation of an enzyme: Co(2+):TGA ternary complex prior to demetallation of the active site. CoLF reported herein constitutes the first spectroscopic probe of LF's active site, which may be utilized in future studies to gain further insight into the enzyme's mechanism and inhibitor interactions., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Limited data suggest that optimal atrioventricular (AV) and interventricular (VV) delays are different at rest than during exercise in patients with heart failure. We assessed the feasibility and reproducibility of an electrogram-based method of optimization called QuickOpt at rest and during exercise., Methods: Patients with a St Jude Medical cardiac resynchronization therapy implantable cardioverter-defibrillator were subjected to a graded treadmill test, and QuickOpt was repeatedly measured prior to, during, and after the exercise., Results: Twenty-four patients (16 males, aged 67.4 ± 7.7 years) participated. At rest, delays (in ms) were 110.4 ± 20.1 for sensed AV delay and -70 (LV pacing first) to +20 (RV pacing first) for VV delay. The changes in QuickOpt-derived delays at rest were not significant despite change in body position. During exercise, QuickOpt-derived AV delays did not change in 11 patients, were shorter during peak exercise in 8 patients, and were longer in 3 patients (average value during peak exercise was 126.5 ± 15.8 ms, P = 0.04 compared to baseline). The QuickOpt-derived VV delay gradually shifted toward earlier right ventricular pacing during exercise in 19 patients, while no changes were seen in 3 patients, and a shift occurred toward earlier left ventricular pacing in 2 patients (average value during peak exercise was -30.7 ± 22.2; P = 0.001 compared to baseline). There was no correlation between changes in the QuickOpt-derived AV and VV delays and heart rate., Conclusions: The application of electrogram-based algorithm is feasible both at rest and during exercise. The results are reproducible. QuickOpt-derived AV and VV delays individually change during exercise., (Copyright © 2011. Published by Elsevier Inc.)

Anthrax lethal factor (LF) is a zinc-dependent metalloendopeptidase previously shown to require calcium and magnesium for the restoration of its catalytic function upon exposure of the apoprotein (apoLF) to Zn(2+). Since concrete Ca(2+)/Mg(2+) binding sites have not been identified in LF, the effects of alkaline earth metals on the enzymatic function of holoLF (ZnLF) and on the reconstitution of apoLF were reinvestigated. The current study reveals alkaline earth metals to be inhibitory at concentrations higher than 1mM. A combination of activity/inhibition assays and Tb(3+) luminescence spectroscopy was employed to unequivocally establish the presence of at least one inhibitory low-affinity Ca(2+)-site in LF. A comparative analysis of apoLF preparations obtained by dialysis and centrifugal filtration (following treatment of ZnLF with chelators) revealed the exposure of apoLF to low equimolar amounts of Zn(2+) to be sufficient for the full restoration of the protein's catalytic competence, a finding constistent with the picomolar dissociation constant of ZnLF determined in this study. The previously documented requirement of Ca(2+) and Mg(2+) in apoLF reconstitution may be explicable on the basis of contamination of dialyzed apoprotein preparations with residual chelator, a phenomenon not encountered with apoLF obtained by centrifugal filtration., (Copyright © 2010 Elsevier Inc. All rights reserved.)