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OBJECTIVE: The general objective of this study was to explore the challenges of establishing an out of hospital cardiac arrest (OOHCA) surveillance program in Canada. More specifically, we attempted to determine the organizational structure of the delivery of emergency medical services (EMS) in Canada, describe the cardiac arrest data collection infrastructure in each province and determine which OOHCA variables are being collected. METHODS: We conducted a national survey of 82 independent EMS health authorities in Canada. Methodology experts devel oped the survey and distribution using a modified Dillman tech nique. We distributed 67 surveys electronically (84%) and the rest by regular mail. We weighted each survey response by the popu lation of the catchment area represented by the responding health authority (2004 census). Descriptive statistics are reported. RESULTS: We received 60 completed surveys, representing a 73% response rate. The responding health authorities' catchment areas represented 80% of the Canadian population (territories excluded). Our survey results highlight a lack of common OOHCA data definitions used among health authorities, sporadic use of data quality assurance procedures, rare linkages to in hospital survival outcomes and potential confidentiality issues. Other chal lenges raised by respondents included determining warehousing location and finding financial resources for a national OOHCA registry. CONCLUSION: Results from this survey demonstrate that, although it is challenging, it is possible to collect OOHCA data and access in hospital survival outcomes. Collaborative efforts with the Resuscitation Outcomes Consortium and other potential provin cial partners should be explored. [ABSTRACT FROM AUTHOR]

Purpose: The population is aging, and age remains an important factor in deciding surgical candidacy for intracranial tumors. The natural history and surgical behavior of meningiomas in octogenarians are not well understood. We evaluated the surgical and functional outcomes, including survival, among octogenarians with intracranial meningiomas in a single institution., Methods: The Tumor Registry (2004-2021) was used to identify octogenarian patients (ages 80-89) diagnosed with intracranial meningioma. Primary endpoints were 1-year survival and functional outcome measured with mRS postsurgery. Kaplan-Meier, univariable Log-rank tests, and multivariable Cox hazards proportional regression models were used for assessing factors associated with overall survival (OS) in octogenarians with meningiomas who underwent surgery; logistic regression and McNemar's were used to further characterize risk factors affecting functional surgical outcome at 1 year., Results: Thirty octogenarians with intracranial meningioma who underwent surgery were identified. Median age was 82.5 years and 66.6% were female patients. The 1-year median postsurgical survival probability for all octogenarians with meningioma was 86.3% and no intraoperative mortality was observed. Frailty (mFI-5, p = 0.84), tumor grade (p = 0.11), tumor size (p = 0.22), extent of resection (p = 0.35), and Karnofsky scale on admission (p = 0.93) did not significantly affect the survival in octogenarians with meningiomas which were treated surgically. The 1-year postoperative functional status of octogenarian meningioma patients who underwent surgery was significantly improved compared to pre-op mRS (McNemar's chi-squared = 9.6, df = 1, p-value = 0.001946)., Conclusion: In octogenarians with meningiomas, surgical intervention significantly improves the pre-operative modified Rankin Scale at 1 year postsurgery in this cohort., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Compared with the Leksell G frame, the new Leksell Vantage stereotactic headframe offers many benefits during deep brain stimulation (DBS) procedures., Objective: To define the "real-world" targeting accuracy of the Vantage frame for performing DBS lead implants., Methods: Retrospective review of all patients who underwent DBS using the Vantage frame with our surgeon between July 2021 and May 2022. Target and actual coordinates of implanted DBS leads were determined in BrainLab., Results: Thirty-three electrode trajectories (17 left-sided, 16 right-sided) were included. On the right, actual electrode placement was, on average, 0.95 mm more medial, 1.06 mm more posterior, and 0.55 mm more superior compared with planned trajectories. The vector error was 1.93 ± 0.91 mm. On the left, actual electrode placement was 0.49 mm more lateral, 0.66 mm more posterior, and 0.67 mm more superior than planned trajectories. The vector error was 1.68 ± 0.66 mm. After excluding all electrodes that were repositioned after microelectrode recording and/or test stimulation, right-sided electrodes (n = 10) were 0.88 mm more medial, 0.94 mm more posterior, and 0.76 mm more superior than planned trajectories. The vector error was 1.74 ± 1.01 mm. Left-sided electrodes (n = 14) were 0.49 mm more lateral, 0.63 mm more posterior, and 0.49 mm more superior than planned trajectories. The vector error was 1.62 ± 0.68 mm., Conclusion: This study demonstrated the accuracy of the Leksell Vantage frame in comparison with the traditional Leksell G frame., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background: Surgical intervention for brain tumor patients aged 80 to 89 years is controversial, as the comorbidities and physiology associated with aging are often thought to increase surgical risks. Surgical outcomes, however, are not well characterized for octogenarians. This review therefore assessed the outcomes and mortality risk associated with tumor removal in octogenarians at our academic institution., Methods: Retrospective review of patients aged 80 to 89 who underwent craniotomy for tumor resection (CTR) at our institution between 2004-2021 and who were diagnosed with meningioma, glioblastoma, or metastatic disease. Primary outcome was 30-day mortality., Results: Sixty-one CTRs were included in analysis. Median age was 83 (interquartile range 81-85) years, and the most common preoperative comorbidity was hypertension (n=44). Most patients (n=35) had a preoperative modified Rankin Scale (mRS) score between 0-2. Seventeen (27.9%) patients experienced postoperative complications (i.e., urinary tract infection, deep venous thrombosis, etc.), and 26.2% (n=16) experienced new-onset neurologic deficits postoperatively (i.e., aphasia, motor deficits, etc.). Upon discharge, most patients (n=43) had an mRS score of 3-4. Within 30 days of surgery, 14.8% (n=9) of patients were readmitted to the hospital and 8.2% (n=5) of patients died: 2 with meningioma, 1 with glioblastoma, and 2 with metastatic disease. The most common cause of death was intracranial hemorrhage (n=3). Three-month mortality was 23.0% (n=14). Mean survival after surgery was 33 months for meningioma patients, 6.9 months for glioblastoma patients, and 15 months for patients with metastatic lesions., Conclusion: Our review found a 30-day mortality rate of 8.2% across all tumor types, and mean survival was similar to that previously reported for patients across all age groups. Surgical intervention for octogenarian tumor patients is therefore feasible, safe, and likely worthwhile for extending and improving lives., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2023 The Korean Brain Tumor Society, The Korean Society for Neuro-Oncology, and The Korean Society for Pediatric Neuro-Oncology.)

Background: Hospital length of stay (LOS) related to craniotomy for tumor resection (CTR) is a marker of neurosurgical quality of care. Limiting LOS benefits both patients and hospitals. This study examined which factors contribute to extended LOS (eLOS) at our academic center., Methods: Retrospective medical record review of 139 consecutive CTRs performed between July 2020 and July 2021. Univariate and multivariable analyses determined which factors were associated with an eLOS (≥8 days)., Results: Median LOS was 6 days (IQR 3-9 days). Fifty-one subjects (36.7%) experienced an eLOS. Upon univariate analysis, potentially modifiable factors associated with eLOS included days to occupational therapy (OT), physical therapy (PT), and case management clearance ( p  < .001); and discharge disposition ( p  < .001). Multivariable analysis revealed that pre-operative anti-coagulant use (OR 10.74, 95% CI 2.64-43.63, p  = .001), Medicare (OR 4.80, 95% CI 1.07-21.52, p  = .04), ED admission (OR 26.21, 95% CI 5.17-132.99, p  < .001), transfer to another service post-surgery (OR 30.00, 95% CI 1.56-577.35, p  = .02), and time to post-operative imaging (OR 2.91, 95% CI 1.27-6.65, p  = .01) were associated with eLOS. Extended LOS was not significantly associated with ED visits ( p  = .45) or unplanned readmissions within 30 days of surgery ( p  = .35), and both ( p  = .04; p  = .04) were less likely following a short LOS (<5 days)., Conclusion: While some factors driving LOS related to CTR are uncontrollable, expedient pre- and post-operative management may reduce LOS without compromising care., Competing Interests: None of the authors have any competing interests regarding this manuscript., (© 2023 Published by Elsevier Inc.)

Global water security is jeopardized by the presence of anthropogenic contaminants, which can persist resiliently in the environment and adversely affect human health. Surface adsorption of polluting species is an effective technique for water purification. In this work, redox-active magnetic compounds were designed for the targeted removal of inorganic and organic anions in water via polymeric redox-active vinylferrocene (VFc) and pyrrole (Py) moieties. An Fe 3 O 4 @SiO 2 @PPy@P(VFc- co -HEMA) composite was prepared in a four-step process, with the outermost layer possessing heightened hydrophilicity as a result of the optimized incorporation of 2-hydroxyethylmethacrylate (HEMA) monomers into the backbone of the ferrocene macromolecule. The synthesized materials are able to separate carcinogenic hexavalent chromium oxyanions and other charged micropollutants, and exhibit a 2-fold or greater enhancement in adsorption uptake once the redox-active ferrocene groups are oxidized to ferrocenium cations, with capacities of 23, 49, 66, and 95 mg/g VFc for maleic acid, 2-(6-methoxy-2-naphthyl)propionic acid (Naproxen), (2,4-dichlorophenoxy)acetic acid (2,4-D), and (2-dodecylbenzene)sulfonic acid (DBS), respectively, and a > 99% extractability of chromium in the 1 ppm range. The application of redox-active components to a magnetic particulate scaffold improves maneuverability and phase contact, giving rise to new potential aqueous separation process frameworks for water or product purification.

Unlike crystalline atomic and ionic solids, texture development due to crystallographically preferred growth in colloidal crystals is less studied. Here we investigate the underlying mechanisms of the texture evolution in an evaporation-induced colloidal assembly process through experiments, modeling, and theoretical analysis. In this widely used approach to obtain large-area colloidal crystals, the colloidal particles are driven to the meniscus via the evaporation of a solvent or matrix precursor solution where they close-pack to form a face-centered cubic colloidal assembly. Via two-dimensional large-area crystallographic mapping, we show that the initial crystal orientation is dominated by the interaction of particles with the meniscus, resulting in the expected coalignment of the close-packed direction with the local meniscus geometry. By combining with crystal structure analysis at a single-particle level, we further reveal that, at the later stage of self-assembly, however, the colloidal crystal undergoes a gradual rotation facilitated by geometrically necessary dislocations (GNDs) and achieves a large-area uniform crystallographic orientation with the close-packed direction perpendicular to the meniscus and parallel to the growth direction. Classical slip analysis, finite element-based mechanical simulation, computational colloidal assembly modeling, and continuum theory unequivocally show that these GNDs result from the tensile stress field along the meniscus direction due to the constrained shrinkage of the colloidal crystal during drying. The generation of GNDs with specific slip systems within individual grains leads to crystallographic rotation to accommodate the mechanical stress. The mechanistic understanding reported here can be utilized to control crystallographic features of colloidal assemblies, and may provide further insights into crystallographically preferred growth in synthetic, biological, and geological crystals., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

The regulation of mass transfer across membranes is central to a wide spectrum of applications. Despite numerous examples of stimuli-responsive membranes for liquid-phase species, this goal remains elusive for gaseous molecules. We describe a previously unexplored gas gating mechanism driven by reversible electrochemical metal deposition/dissolution on a conductive membrane, which can continuously modulate the interfacial gas permeability over two orders of magnitude with high efficiency and short response time. The gating mechanism involves neither moving parts nor dead volume and can therefore enable various engineering processes. An electrochemically mediated carbon dioxide concentrator demonstrates proof of concept by integrating the gating membranes with redox-active sorbents, where gating effectively prevented the cross-talk between feed and product gas streams for high-efficiency, directional carbon dioxide pumping. We anticipate our concept of dynamically regulating transport at gas-liquid interfaces to broadly inspire systems in fields of gas separation, miniaturized devices, multiphase reactors, and beyond., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

The rising use of seawater desalination for fresh water production is driving a parallel rise in the discharge of high-salinity brine into the ocean. Better utilization of this brine would have a positive impact on the energy use, cost, and environmental footprint of desalination. Furthermore, intermittent renewable energy can easily power the brine utilization and, for reverse osmosis technology, the entire desalination plant. One pathway toward these goals is to convert the otherwise discharged brine into useful chemicals; waste could be transformed into sodium hydroxide or caustic soda (NaOH) and hydrochloric acid (HCl). In this Minireview, we discuss opportunities and challenges for integrated valorization of desalination brine through NaOH and HCl recovery., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The electrochemical CO 2 reduction reaction (CO2RR) has gained attention recently due to rising concern over atmospheric carbon levels, but catalyst selectivity and efficiency remain a challenge, particularly for products other than CO. Here, we report the selective formation of formate using a sulfide-derived copper (SD-Cu) catalyst for CO2RR. On the basis of in situ and postelectrolysis spectroscopy, we propose that this selectivity is due to stronger binding of the CO intermediate originating from remaining subsurface sulfur atoms.

In order to prepare lubricant-infused repellent coatings on silica nanostructures using low vapor pressure ionic liquids as lubricants, we study the wetting behavior of a set of imidazolium-based ionic liquids with different alkyl side chains as a function of the applied surface functionalities. We take advantage of the structural color of inverse opals prepared from a colloidal coassembly technique to study the infiltration of ionic liquids into these nanoporous structures. We find that the more hydrophobic ionic liquids with butyl and hexyl side chains can completely infiltrate inverse opals functionalized with mixed self-assembled monolayers composed of imidazole groups and aliphatic hydrocarbon chains, which we introduce via silane chemistry. These molecular species reflect the chemical nature of the ionic liquid, thereby increasing the affinity between the liquid and solid surface. The mixed surface chemistry provides sufficiently small contact angles with the ionic liquid to infiltrate the nanopores while maximizing the contact angle with water. As a result, the mixed monolayers enable the design of a stable ionic liquid/solid interface that is able to repel water as a test liquid. Our results underline the importance of matching chemical affinities to predict and control the wetting behavior in complex, multiphase systems.

Inorganic microstructured materials are ubiquitous in nature. However, their formation in artificial self-assembly systems is challenging as it involves a complex interplay of competing forces during and after assembly. For example, colloidal assembly requires fine-tuning of factors such as the size and surface charge of the particles and electrolyte strength of the solvent to enable successful self-assembly and minimize crack formation. Co-assembly of templating colloidal particles together with a sol-gel matrix precursor material helps to release stresses that accumulate during drying and solidification, as previously shown for the formation of high-quality inverse opal (IO) films out of amorphous silica. Expanding this methodology to crystalline materials would result in microscale architectures with enhanced photonic, electronic, and catalytic properties. This work describes tailoring the crystallinity of metal oxide precursors that enable the formation of highly ordered, large-area (mm 2 ) crack-free titania, zirconia, and alumina IO films. The same bioinspired approach can be applied to other crystalline materials as well as structures beyond IOs., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Nature evolved a variety of hierarchical structures that produce sophisticated functions. Inspired by these natural materials, colloidal self-assembly provides a convenient way to produce structures from simple building blocks with a variety of complex functions beyond those found in nature. In particular, colloid-based porous materials (CBPM) can be made from a wide variety of materials. The internal structure of CBPM also has several key attributes, namely porosity on a sub-micrometer length scale, interconnectivity of these pores, and a controllable degree of order. The combination of structure and composition allow CBPM to attain properties important for modern applications such as photonic inks, colorimetric sensors, self-cleaning surfaces, water purification systems, or batteries. This review summarizes recent developments in the field of CBPM, including principles for their design, fabrication, and applications, with a particular focus on structural features and materials' properties that enable these applications. We begin with a short introduction to the wide variety of patterns that can be generated by colloidal self-assembly and templating processes. We then discuss different applications of such structures, focusing on optics, wetting, sensing, catalysis, and electrodes. Different fields of applications require different properties, yet the modularity of the assembly process of CBPM provides a high degree of tunability and tailorability in composition and structure. We examine the significance of properties such as structure, composition, and degree of order on the materials' functions and use, as well as trends in and future directions for the development of CBPM.

Materials in nature are characterized by structural order over multiple length scales have evolved for maximum performance and multifunctionality, and are often produced by self-assembly processes. A striking example of this design principle is structural coloration, where interference, diffraction, and absorption effects result in vivid colors. Mimicking this emergence of complex effects from simple building blocks is a key challenge for man-made materials. Here, we show that a simple confined self-assembly process leads to a complex hierarchical geometry that displays a variety of optical effects. Colloidal crystallization in an emulsion droplet creates micron-sized superstructures, termed photonic balls. The curvature imposed by the emulsion droplet leads to frustrated crystallization. We observe spherical colloidal crystals with ordered, crystalline layers and a disordered core. This geometry produces multiple optical effects. The ordered layers give rise to structural color from Bragg diffraction with limited angular dependence and unusual transmission due to the curved nature of the individual crystals. The disordered core contributes nonresonant scattering that induces a macroscopically whitish appearance, which we mitigate by incorporating absorbing gold nanoparticles that suppress scattering and macroscopically purify the color. With increasing size of the constituent colloidal particles, grating diffraction effects dominate, which result from order along the crystal's curved surface and induce a vivid polychromatic appearance. The control of multiple optical effects induced by the hierarchical morphology in photonic balls paves the way to use them as building blocks for complex optical assemblies--potentially as more efficient mimics of structural color as it occurs in nature.

We present a simple one-pot co-assembly method for the synthesis of hierarchically structured pigment particles consisting of silica inverse-opal bricks that are doped with plasmonic absorbers. We study the interplay between the plasmonic and photonic resonances and their effect on the visual appearance of macroscopic collections of photonic bricks that are distributed in randomized orientations. Manipulating the pore geometry tunes the wavelength- and angle-dependence of the scattering profile, which can be engineered to produce angle-dependent Bragg resonances that can either enhance or contrast with the color produced by the plasmonic absorber. By controlling the overall dimensions of the photonic bricks and their aspect ratios, their preferential alignment can either be encouraged or suppressed. This causes the Bragg resonance to appear either as uniform color travel in the former case or as sparse iridescent sparkle in the latter case. By manipulating the surface chemistry of these photonic bricks, which introduces a fourth length-scale (molecular) of independent tuning into our design, we can further engineer interactions between liquids and the pores. This allows the structural color to be maintained in oil-based formulations, and enables the creation of dynamic liquid-responsive images from the pigment.

Porous materials display interesting transport phenomena due to restricted motion of fluids within the nano- to microscale voids. Here, we investigate how liquid wetting in highly ordered inverse opals is affected by anisotropy in pore geometry. We compare samples with different degrees of pore asphericity and find different wetting patterns depending on the pore shape. Highly anisotropic structures are infiltrated more easily than their isotropic counterparts. Further, the wetting of anisotropic inverse opals is directional, with liquids filling from the side more easily. This effect is supported by percolation simulations as well as direct observations of wetting using time-resolved optical microscopy.

The photofragmentation of butyrophenone yields benzoate and a propyl radical on oxidized TiO2(110). Oxygen dissociates in native oxygen vacancies to produce reactive oxygen adatoms which react with butyrophenone to create photoactive butyrophenone-O complexes that are sensitive to hole oxidation created upon UV illumination. The same O adatoms also trap one of the primary photoproducts, phenyl-CO, to produce benzoate. The reaction proceeds via a Norrish Type I like process involving α-CC cleavage on the surface, in contrast to the gas phase where a Norrish Type II pathway predominates. The mechanism is probed using mass spectrometry and, for the first time, scanning tunneling microscopy (STM). Our STM experiments show that there is a 1-to-1 correspondence between the immobile butyrophenone-O complex and formation of a benzoate on the surface. We also demonstrate that the benzoate species is in close proximity to the original butyrophenone complex, indicating that benzoate is produced on a time scale more rapid than diffusion of the photoproducts. While the photoproducts of butyrophenone decomposition are similar to ketone oxidation reported previously, butyrophenone reacts via a different starting ground state, based on STM and density functional theory studies. Specifically, butyrophenone does not produce a dioxyalkylene species, which has been proposed to be the photoactive state for other ketones. Based on a combination of STM experiments and density functional theory, we propose that a peroxy-like configuration where the oxygen adatom stabilizes the butyrophenone through its carbonyl oxygen is the surface intermediate that photodecomposes. These results demonstrate the importance of the excited state in determining the photochemistry of ketones on surfaces.

Methyl formate is produced from the photo-oxidation of methanol on preoxidized TiO(2)(110). We demonstrate that two consecutive photo-oxidation steps lead to methyl formate using mass spectrometry and scanning tunneling microscopy. The first step in methanol oxidation is formation of methoxy by the thermal dissociation of the O-H bond to yield adsorbed CH(3)O and water. Formaldehyde is produced via hole-mediated oxidation of adsorbed methoxy in the first photochemical step. Next, transient HCO is made photochemically from formaldehyde. The HCO couples with residual methoxy on the surface to yield methyl formate. Exposure of the titania surface to O(2) is required for these photo-oxidation steps in order to heal surface and near-surface defects that can serve as hole traps. Notably, residual O adatoms are not required for photochemical production of methyl formate or formaldehyde. All O adatoms react thermally with methanol to form methoxy and gaseous water at rt, leaving a surface devoid of O adatoms. The mechanism provides insight into the photochemistry of TiO(2) and suggests general synthetic pathways that are the result of the ability to activate both alkoxides and aldehydes using photons.

Background: The valve-in-valve (VinV) procedure is a minimally invasive, transcatheter, off-pump, alternative to conventional valve replacement, which uses a failing bioprosthesis to anchor a second transcatheter-delivered prosthesis. This technique appears effective for prolonging freedom from reintervention and treating early device failure. However, it is unknown as to how long reintervention can be avoided., Methods: We present the pathological findings of a VinV explanted after 47 months, as well as the failure modes of these devices., Results: The VinV approach in our case ultimately failed, likely due to the proximity of the host's tissues to the prosthetic device, resulting in a combination of pannus, calcification, and a cusp tear., Conclusions: Additional long-term follow-up of pulmonary VinV implantations is needed in order to determine the life span of VinVs and what causes them to fail., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The effect of trough levels of a monoclonal antibody drug (drugB) on screening cut point (CP) determination for an anti-drug antibody (ADA) assay was scrutinized and the conclusions substantiated by data from a phase 3 cancer clinical study. The ADA assay utilized an acid dissociation step and either 0 or 100 μg/ml drugB was added to the samples prior to obtaining the signals used for CP calculations. Serum samples from three different drug-naive populations were tested (healthy individuals, cancer patients enrolled in the drugB clinical trial and cancer patients whose serum samples were available commercially). For the same disease state samples, both the screening CP and confirmation CP were different when calculated during validation or from study sample analysis. It is reasonable to assume that variability was due to the patient heterogeneity, as they could have been at distinct stages of disease progression, and/or taking different medications, amongst other differences. The patients enrolled in the clinical trial were stratified as per protocol and hence represented a more homogeneous population. Drug effects on CP may be population dependent and also assay dependent., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Nulojix(®) is a fusion protein composed of the Fc portion of a human IgG1 linked to the extracellular modified domain of CTLA-4. Nulojix differs from another Bristol Myers Squibb product, Orencia(®) by two amino acids and was approved by the FDA on 15 June 2011 for the prophylaxis of organ rejection in adult patients receiving kidney transplant., Results: A sandwich ELISA utilizing two monoclonal antibodies against CTLA-4 was employed for Nulojix quantification and pharmacokinetic analysis. At least 17 analysts have qualified on the assay and contributed to reportable results over the last 7 years. In-study accuracy and precision demonstrate suitable performance: %bias within -4 to 4%, %CV ≤13% and total error within 6-15%. Incurred sample reanalysis was completed in applicable disease-state populations. The assay was automated and validated in additional clinical matrices (ascites and urine) and Nulojix quantification was validated in the presence of clinically relevant co-administered compounds. In 2011, the biotinylation procedure was modified meriting a regression change (quadratic to 4-parameter logistic) and associated partial validation., Conclusion: This long-term pharmacokinetic program provides a good example of the dynamic clinical environment and adaptation requirements of ligand-binding assays.

Background: The Medtronic Freestyle valve is a stentless porcine valve with reportedly excellent clinical and hemodynamic results, but little has been reported about its long-term pathology., Methods: Seventeen Freestyle valves were explanted (from 2003 to 2009) and reviewed to assess reasons for bioprosthesis failure. All valves were examined in detail, using histochemistry and immunohistochemistry to identify morphological changes, as well as cellular and humoral responses., Results: One Freestyle valve, explanted for mitral valve endocarditis on the fifth postoperative day, was excluded from analysis. The average implant duration was 71.1±35.2 months. Six valves were explanted for infective endocarditis, six for aortic insufficiency, and four for aortic stenosis. Calcification was seen in 11 explants, pannus in 15, thrombus in 12, cusp tears in 9, and 10 explants showed needle tract-like injuries. A chronic inflammatory reaction involving the xenograft arterial wall was seen in 15 of 16 valves. The cells were composed of macrophages and lymphocytes, including T cells (CD8 positive) and B cells. Significant damage to the porcine aortic wall was seen in 15 cases, and cusp myocardial shelf damage in 7 cases. All cases stained positively for IgG and C4dpar., Conclusions: The porcine aortic tissue showed T cell-mediated rejection and significant aortic medial damage, consistent with dilatation of the porcine aortic root. The demonstration of IgG suggests the likelihood of humoral rejection, in addition to cellular rejection. One of the underlying possibilities is that the porcine aortic tissues are inadequately fixed, hence the retained antigenicity., (Copyright © 2012. Published by Elsevier Inc.)

We report a case of a 51-year-old man who was transferred from a community hospital to our institution in cardiogenic shock after thrombolytic therapy for myocardial infarction. At autopsy, a cor triatriatum sinister was found. This may have contributed to his poor outcome post infarction., (Copyright © 2011 Elsevier Inc. All rights reserved.)

A significant location affected by giant cell (GC) arteritis is the ascending aorta, where aneurysms may develop and catastrophic ruptures and acute dissections can occur. Herein, we discuss three cases of GC aortitis discovered at pathological examination of surgically excised aortic aneurysmal tissue. There was no clinical suspicion of any underlying inflammatory process. We describe the main clinical features of the patients in conjunction with a review of the literature to identify any common clinical presentations that manifest in these patients. Giant cell aortitis in the absence of previously established GC arteritis is difficult to identify, and a careful analysis of the history and presentation along with appropriate investigations (e.g., erythrocyte sedimentation rate) may prompt the clinician to consider GC aortitis and suggest immunosuppressant therapy., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Papillary fibroelastomas (PFEs) are benign cardiac tumours that typically arise on diseased aortic or mitral valves. Usually solitary, PFEs are characterised by numerous frond-like branches attached to the valve surface by a single stalk, elastic tissue present within the central core, and the appearance of a sea anemone when immersed in water. PFEs have a predilection for men with a mean age of 56 years. A very rare case of a 25-year-old man with multiple lesions on the aortic and mitral valves and a large confluent "carpet-like" lesion in the left ventricular cavity is presented. Admitted with a significant left middle cerebral artery stroke and hemiplegia, investigations showed a left ventricular outflow tract lesion, with surgical excision displaying a multifocal "carpet-like" PFE. Histopathological examination showed various lesions presenting with a short stem, several fronds arising from each stem like a "tree trunk", and elastic tissue within the central core. This case is presented, along with a review of 833 reported cases of PFEs published after the year 2001. It is believed that this is the first reported instance of surgically resected and morphologically confirmed multiple PFEs seen and removed at one operation.

Myosin-1c is an unconventional myosin involved in hair-cell mechanotransduction, a process that underlies our senses of hearing and balance. To study the interaction of myosin-1c with other components of the hair-cell transduction complex, we have developed an in situ binding assay that permits visualization of myosin-1c binding to hair-cell proteins. In this chapter we describe in detail the methods needed for the expression and purification of recombinant myosin-1c fragments and their use in the in situ binding assay.

The identities of some of the constituents of the hair-cell transduction apparatus have been elucidated only recently. The molecular motor myosin-1c (Myo1c) functions in adaptation of the hair-cell response to sustained mechanical stimuli and is therefore an integral part of the transduction complex. Recent data indicate that Myo1c interacts in vitro with two other molecules proposed to be important for transduction: cadherin 23 (Cdh23), a candidate for the stereociliary tip link, and phosphatidylinositol 4,5-bisphosphate (PIP2), which is abundant in the membranes of hair-cell stereocilia. It is not known, however, whether these interactions occur in hair cells. Using an in situ binding assay on saccular hair cells, we demonstrated previously that Myo1c interacts with molecules at stereociliary tips, the site of transduction, through sequences contained within its calmodulin (CaM)-binding neck domain, which can bind up to four CaM molecules. In the current study, we identify the second CaM-binding IQ domain as a region of Myo1c that mediates CaM-sensitive binding to stereociliary tips and to PIP2 immobilized on a solid support. Binding of Myo1c to stereociliary tips of cochlear and vestibular hair cells is disrupted by treatments that break tip links. In addition, Myo1c does not bind to stereocilia from mice whose hair cells lack Cdh23 protein despite the presence of PIP2 in the stereociliary membranes. Collectively, our data suggest that Myo1c and Cdh23 interact at the tips of hair-cell stereocilia and that this interaction is modulated by CaM.

3D domain swapping of proteins involves the interconversion of a monomer containing a single domain-domain interface and a 2-fold symmetrical dimer containing two equivalent intermolecular interfaces. Human glyoxalase I has the structure of a domain-swapped dimer [Cameron, A. D., Olin, B., Ridderström, M., Mannervik, B., and Jones, T. A. (1997) EMBO J. 16, 3386-3395] but Pseudomonas putida glyoxalase I has been reported to be monomeric [Rhee, H.-I., Murata, K., and Kimura, A. (1986) Biochem. Biophys. Res. Commun. 141, 993-999]. We show here that recombinant P. putida glyoxalase I is an active dimer (kcat approximately 500 +/- 100 s-1; KM approximately 0.4 +/- 0.2 mM) with two zinc ions per dimer. The zinc is required for structure and function. However, treatment of the dimer with glutathione yields an active monomer (kcat approximately 115 +/- 40 s-1; KM approximately 1.4 +/- 0.4 mM) containing a single zinc ion. The monomer is metastable and slowly reverts to the active dimer in the absence of glutathione. Thus, glyoxalase I appears to be a novel example of a single protein able to exist in two alternative domain-swapped forms. It is unique among domain-swapped proteins in that the active site and an essential metal binding site are apparently disassembled and reassembled by the process of domain swapping. Furthermore, it is the only example to date in which 3D domain swapping can be regulated by a small organic ligand.

Data on critical frequency of photic driving (CFPD), frequency following response (FFR), and visual, somatosensory (peroneal nerve), and brain-stem auditory evoked potentials (EPs) were obtained from 20 patients who had clinically definite multiple sclerosis and ten healthy normal subjects in a controlled, balanced study under normothermic and hyperthermic (+1 degrees C) conditions with a test-retest interval of one week. Normal subjects' test results showed no changes during hyperthermia. Patients' EP and CFPD data correlated well with history, clinical signs, and symptoms during both normothermia and hyperthermia. The FFR test data were equivocal and not fully analyzed. Data from the four other tests showed additional patient abnormalities during hyperthermia. Multimodality testing increased the number of patient abnormalities compared with single tests, and the number increased further during hyperthermia. Test-retest reproducibility was higher during hyperthermia.

As a guide to both strain and process improvement and based on certain assumptions concerning both glucose and energy metabolism of the process organism, Alcaligenes faecalis var. myxogenes, the theoretical "maximum" carbon (glucose) substrate to product conversion efficiency (i.e., product yield) has been estimated for "curdlan-type" beta(1 leads to 3)-glucan exopolysaccharide production in batch fermentations. Under nitrogen limitation, which promotes curdlan biosynthesis (mu = 0), the rate of glucose consumption for cellular maintenance energy (grams of glucose per gram of cells per hour) was approximately five times higher than under carbon limitation. The decrease in the theoretical "maximum" curdlan conversion efficiency of 74% to the average value of 50-56% was due primarily to the high maintenance coefficient of the nitrogen-starved culture.

The biosynthesis of a thermogelable, extracellular homo-beta-(1 leads to 3)-glucan called "curdlan," has been studied in batch and continuous cultures of Alcaligenes faecalis var. myxogenes. Curdlan production is associated with the poststationary phase of a nitrogen-depleted, aerobic batch culture. Exopolymer is not detected in single-stage, carbon-limited continuous cultures but curdlan can be isolated from the effluent of a nitrogen-limited chemostat operating at a dilution rate (D) of less than 0.1 h-1. A spontaneous variant of strain ATCC 21680 was isolated and found to be compatible with long-term, nitrogen-limited chemostat culture. The specific rate of curdlan production is approximately four times higher in poststationary batch cultures than in single-stage continuous fermentations. The product yield (Yp/S) associated with batch processing (nongrowing cultures) is approximately 0.5 g curdlan/g glucose, with CO2 being the only detectable by-product.