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Background: The older adult age group makes up one of the fastest-growing groups of individuals with inflammatory bowel disease (IBD). It is important to hear the perspectives of older adults living with IBD about care experiences and managing their illness. The purpose of this patient-oriented study was to identify and prioritize patient-centred strategies that have the potential to enhance IBD-related care for older adults in Saskatchewan., Methods: The interprofessional research team, consisting of older adult individuals living with IBD, gastroenterology providers, and researchers specializing in IBD or older adult education used a modified Delphi approach to identify and prioritize strategies that may enhance IBD-related care for older adults. Thirty-one older adults with IBD participated in ranking, revising, and prioritizing statements related to their chronic illness care. Nine statements were developed that highlighted strategies for older adult IBD care., Results: Through the consensus process, 6 statements were retained. Co-creating a treatment plan with the IBD provider was ranked as the top priority statement for older adults with IBD., Conclusion: Facilitating collaborative relationships and understanding individual priorities for IBD-related care for older adults has the potential to enhance positive health outcomes and quality of life for these individuals., Competing Interests: N.R. has received speaker fees from Abbvie, Amgen, and CANIBD. S.F. has received consulting fees from Abbvie, Janssen, Takeda, Pendopharm, Pfizer, Amgen, Sandoz, and Eli Lilly. S.F. has received payment from Abbvie, Janssen, Takeda, Pendopharm, Pfizer. S.F. has received support or attending meetings and/or travel from Pfizer. C.R.-C. has received consulting fees from Takeda. C.R.-C. has received support or attending meetings and/or travel from Pfizer. D.M., J.-N.P.-S., N.T., and J.W. declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Canadian Association of Gastroenterology.)

Compositionally complex materials such as high-entropy alloys and oxides have the potential to be efficient platforms for catalyst discovery because of the vast chemical space spanned by these novel materials. Identifying the composition of the most active catalyst materials, however, requires unraveling the descriptor-activity relationship, as experimentally screening the multitude of possible element ratios quickly becomes a daunting task. In this work, we show that inferred adsorption energy distributions of *OH and *O on complex solid solution surfaces within the space spanned by the system Ag-Pd-Pt-Ru are coupled to the experimentally observed electrocatalytic performance for the oxygen reduction reaction. In total, the catalytic activity of 1582 alloy compositions is predicted with a cross-validated mean absolute error of 0.042 mA/cm 2 by applying a theory-derived model with only two adjustable parameters. Trends in the discrepancies between predicted electrochemical performance values of the model and the measured values on thin film surfaces subsequently provide insight into the alloys' surface compositions during reaction conditions. Bridging this gap between computationally modeled and experimentally observed catalytic activities, not only reveals insight into the underlying theory of catalysis but also takes a step closer to realizing exploration and exploitation of high-entropy materials., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

High entropy alloys (HEAs) are an important new material class with significant application potential in catalysis and electrocatalysis. The entropy-driven formation of HEA materials requires high temperatures and controlled cooling rates. However, catalysts in general also require highly dispersed materials, i.e. , nanoparticles. Only then a favorable utilization of the expensive raw materials can be achieved. Several recently reported HEA nanoparticle synthesis strategies, therefore, avoid the high-temperature regime to prevent particle growth. In our work, we investigate a system of five noble metal single-source precursors with superior catalytic activity for the oxygen reduction reaction. Combining in situ X-ray powder diffraction with multi-edge X-ray absorption spectroscopy, we address the fundamental question of how single-phase HEA nanoparticles can form at low temperatures. It is demonstrated that the formation of HEA nanoparticles is governed by stochastic principles and the inhibition of precursor mobility during the formation process favors the formation of a single phase. The proposed formation principle is supported by simulations of the nanoparticle formation in a randomized process, rationalizing the experimentally found differences between two-element and multi-element metal precursor mixtures., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

The derivation of neuronal lineage cells from human induced pluripotent stem cells (hiPSCs) marked a milestone in brain research. Since their first advent, protocols have been continuously optimized and are now widely used in research and drug development. However, the very long duration of these conventional differentiation and maturation protocols and the increasing demand for high-quality hiPSCs and their neural derivatives raise the need for the adoption, optimization, and standardization of these protocols to large-scale production. This work presents a fast and efficient protocol for the differentiation of genetically modified, doxycycline-inducible neurogenin 2 (iNGN2)-expressing hiPSCs into neurons using a benchtop three-dimensional (3D) suspension bioreactor. In brief, single-cell suspensions of iNGN2-hiPSCs were allowed to form aggregates within 24 h, and neuronal lineage commitment was induced by the addition of doxycycline. Aggregates were dissociated after 2 days of induction and cells were either cryopreserved or replated for terminal maturation. The generated iNGN2 neurons expressed classical neuronal markers early on and formed complex neuritic networks within 1 week after replating, indicating an increasing maturity of neuronal cultures. In summary, a detailed step-by-step protocol for the fast generation of hiPSC-derived neurons in a 3D environment is provided that holds great potential as a starting point for disease modeling, phenotypic high-throughput drug screenings, and large-scale toxicity testing.

Induced pluripotent stem cell (iPSC) technology enabled the production of pluripotent stem cell lines from somatic cells from a range of known genetic backgrounds. Their ability to differentiate and generate a wide variety of cell types has resulted in their use for various biomedical applications, including toxicity testing. Many of these iPSC lines are now registered in databases and stored in biobanks such as the European Bank for induced pluripotent Stem Cells (EBiSC), which can streamline the quality control and distribution of these individual lines. To generate the quantities of cells for banking and applications like high-throughput toxicity screening, scalable and robust methods need to be developed to enable the large-scale production of iPSCs. 3D suspension culture platforms are increasingly being used by stem cell researchers, owing to a higher cell output in a smaller footprint, as well as simpler scaling by increasing culture volume. Here we describe our strategies for successful scalable production of iPSCs using a benchtop bioreactor and incubator for 3D suspension cultures, while maintaining quality attributes expected of high-quality iPSC lines. Additionally, to meet the increasing demand for "ready-to-use" cell types, we report recent work to establish robust, scalable differentiation protocols to cardiac, neural, and hepatic fate to enable EBiSC to increase available research tools., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Hepatocytes are of special interest in biomedical research for disease modelling, drug screening and in vitro toxicology. Human induced pluripotent stem cell (hiPSC)-derived hepatocytes could complement primary human hepatocytes due to their capability for large-scale expansion. In this study, we present an optimized protocol for the generation of hepatocyte-like cells (HLCs) from hiPSC in monolayer (2D) and suspension culture (3D) for production of organoids. A protocol was initially optimized in 2D using a gene edited CYP3A4 Nanoluciferase reporter hiPSC line for monitoring the maturity of HLCs and cryopreservation of definitive endoderm (DE) cells. The protocol was optimized for microwell cultures for high-throughput screening to allow for a sensitive and fast readout of drug toxicity. To meet the increasing demand of hepatic cells in biomedical research, the differentiation process was furthermore translated to scalable suspension-based bioreactors for establishment of hepatic organoids. In pilot studies, the technical settings have been optimized by adjusting the initial seeding density, rotation speed, inoculation time, and medium viscosity to produce homogeneous hepatic organoids and to maximize the biomass yield (230 organoids/ml). To speed up the production process, cryopreservation approaches for the controlled freezing of organoids were analysed with respect to cell recovery and marker expression. The results showed that cryopreserved organoids maintained their phenotype only when derived from hepatocyte progenitors (HPs) at day 8 but not from more mature stages. The establishment of robust protocols for the production of large batches of hepatocytes and hepatic organoids could substantially boost their use in biomedical and toxicology studies., (Copyright © 2022. Published by Elsevier Inc.)

Active, selective and stable catalysts are imperative for sustainable energy conversion, and engineering materials with such properties are highly desired. High-entropy alloys (HEAs) offer a vast compositional space for tuning such properties. Too vast, however, to traverse without the proper tools. Here, we report the use of Bayesian optimization on a model based on density functional theory (DFT) to predict the most active compositions for the electrochemical oxygen reduction reaction (ORR) with the least possible number of sampled compositions for the two HEAs Ag-Ir-Pd-Pt-Ru and Ir-Pd-Pt-Rh-Ru. The discovered optima are then scrutinized with DFT and subjected to experimental validation where optimal catalytic activities are verified for Ag-Pd, Ir-Pt, and Pd-Ru binary alloys. This study offers insight into the number of experiments needed for optimizing the vast compositional space of multimetallic alloys which has been determined to be on the order of 50 for ORR on these HEAs., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Neurogenin 2 encodes a neural-specific transcription factor (NGN2) able to drive neuronal fate on somatic and stem cells. NGN2 is expressed in neural progenitors within the developing central and peripheral nervous systems. Overexpression of NGN2 in human induced pluripotent stem cells (hiPSCs) or human embryonic stem cells has been shown to efficiently trigger conversion to neurons. Here we describe two gene-edited hiPSC lines harbouring a doxycycline (DOX)-inducible cassette in the AAVS1 locus driving expression of NGN2 (BIONi010-C-13) or NGN2-T2A-GFP (BIONi010-C-15). By introducing NGN2-expressing cassette, we reduce variability associated with conventional over-expression methods such as viral transduction, making these lines amenable for scale-up production and screening processes. DOX-treated hiPSCs convert to neural phenotype within one week and display the expression of structural neuronal markers such as Beta-III tubulin and tau. We performed functional characterization of NGN2-neurons co-cultured with hiPSC-derived astrocytes in a "fully-humanized" set up. Passive properties of NGN2-neurons were indistinguishable from mouse primary cells while displaying variable activity in extracellular recordings performed in multi-electrode arrays (MEAs). We demonstrate that hiPSC-derived astrocytes and neurons can be co-cultured and display functional properties comparable to the gold standard used in electrophysiology. Both lines are globally available via EBiSC repository at https://cells.ebisc.org/., (Copyright © 2021 Janssen Pharmaceutica NV. Published by Elsevier B.V. All rights reserved.)

APOE genotype is the strongest genetic risk factor for Alzheimer's Disease (AD). The low degree of homology between mouse and human APOE is a concerning issue in preclinical models currently used to study the role of this gene in AD pathophysiology. A key objective of ADAPTED (Alzheimer's Disease Apolipoprotein Pathology for Treatment Elucidation and Development) project was to generate in vitro models that better recapitulate human APOE biology. We describe a new set of induced pluripotent stem cells (iPSC) lines carrying common APOE variants (Ɛ2, Ɛ3, and Ɛ3/Ɛ4) and a knock-out isogenic to the parental APOE Ɛ4/Ɛ4 line (UKBi011-A)., (Copyright © 2021 Janssen Pharmaceutica, NV. Published by Elsevier B.V. All rights reserved.)

Neurog2 is the gene encoding the neuronal transcription factor NGN2, which can convert stem cells into functional neurons in a fast and efficient way. Here we report the generation of two iPS cell lines, where DOX inducible constructs of neurog2 either without or with T2A-eGFP were inserted into the safe-site locus AAVS1. These iPS cell lines, BIONi010-C-13 and BIONi010-C-15, respectively, stay pluripotent without DOX but differentiate to (GFP positive) neurons when DOX is added without the need of differentiation factors., (Copyright © 2021 Janssen Pharmaceutica. Published by Elsevier B.V. All rights reserved.)

Complex solid solutions ("high entropy alloys"), comprising five or more principal elements, promise a paradigm change in electrocatalysis due to the availability of millions of different active sites with unique arrangements of multiple elements directly neighbouring a binding site. Thus, strong electronic and geometric effects are induced, which are known as effective tools to tune activity. With the example of the oxygen reduction reaction, we show that by utilising a data-driven discovery cycle, the multidimensionality challenge raised by this catalyst class can be mastered. Iteratively refined computational models predict activity trends around which continuous composition-spread thin-film libraries are synthesised. High-throughput characterisation datasets are then used as input for refinement of the model. The refined model correctly predicts activity maxima of the exemplary model system Ag-Ir-Pd-Pt-Ru. The method can identify optimal complex-solid-solution materials for electrocatalytic reactions in an unprecedented manner., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Ligand and strain effects can tune the adsorption energy of key reaction intermediates on a catalyst surface to speed up rate-limiting steps of the reaction. As novel fields like high-entropy alloys emerge, understanding these effects on the atomic structure level is paramount: What atoms near the binding site determine the reactivity of the alloy surface? By statistical analysis of 2000 density functional theory calculations and subsequent host/guest calculations, it is shown that three atomic positions in the third layer of an fcc(111) metallic structure fourth-nearest to the adsorption site display significantly increased influence on reactivity over any second or third nearest atomic positions. Subsequently observed in multiple facets and host metals, the effect cannot be explained simply through the d-band model or a valence configuration model but rather by favorable directions of interaction determined by lattice geometry and the valence difference between host and guest elements. These results advance the general understanding of how the electronic interaction of different elements affect adsorbate-surface interactions and will contribute to design principles for rational catalyst discovery of better, more stable and energy efficient catalysts to be employed in energy conversion, fuel cell technologies, and industrial processes., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Competing Interests: Intérêts concurrents: Sean Wharton signale avoir reçu des honoraires et le remboursement de frais de voyage et participé à des comités consultatifs universitaires pour Novo Nordisk, Bausch Health, Eli Lilly et Janssen. Sean Wharton est aussi le directeur médical d’une clinique spécialisée en gestion du poids et du diabète. David Lau signale avoir reçu des subventions et un soutien à la recherche d’AstraZeneca, de Novo Nordisk et des Instituts de recherche en santé du Canada (IRSC); des honoraires de conférencier d’AstraZeneca, Bausch Health, Boehringer Ingelheim, Diabète Canada, Eli Lilly, Merck et Novo Nordisk; et des honoraires de consultant d’Amgen, AstraZeneca, Bausch Health, Boehringer Ingelheim, Gilead, HLS Therapeutics, Janssen, Eli Lilly et Novo Nordisk. Michael Vallis est membre de comités consultatifs pour Novo Nordisk, Bausch Health et LifeScan. Michael Vallis a aussi reçu des honoraires de consultant de Bausch Health, LifeScan, Novo Nordisk et Sanofi et des honoraires de conférencier de Novo Nordisk, Sanofi, Bausch Health, Abbott et AbbVie. Arya Sharma signale avoir reçu des honoraires de conférencier et de consultant de Novo Nordisk, Bausch Pharmaceuticals et AstraZeneca. Laurent Biertho signale avoir reçu des subventions de Johnson and Johnson et de Medtronic, et il est membre de comités consultatifs pour Novo Nordisk et Bausch Health, en dehors des travaux soumis. Denise Campbell-Scherer est à l’emploi de l’Université de l’Alberta (professeure au Département de médecine familiale). Elle ne signale aucun autre lien de nature financière, mais mentionne avoir reçu des subventions de recherche de la part des organisations suivantes au cours des trois dernières années : Novo Nordisk Alberta Diabetes Fund (NOVAD), une subvention conjointe accordée après examen par les pairs, en partenariat avec la Fondation de l’Hôpital universitaire, Novo Nordisk et Alberta Innovates; Alberta Innovates Health Solutions (concours lancés par Cancer Prevention Research Opportunity and Collaborative Research et par Innovation Opportunities), les IRSC (concours Stratégie de recherche axée sur le patient du Canada et Des connaissances à la pratique); le Northern Alberta Family Medicine Fund; et l’Alberta Cancer Prevention and Legacy Fund. Elle signale aussi avoir reçu du financement pour le transfert des connaissances des sources suivantes au cours des trois dernières années : subvention à la formation versée sans restriction par Obésité Canada, financée par Novo Nordisk Global; bourse aux fins de réunion du Réseau mondial d’universités; subvention de l’Agency for Healthcare Research and Quality R13 pour une recherche sur l’efficacité des soins de santé et les résultats; une subvention pour la formation médicale des Services de santé de l’Alberta et de l’Association médicale de l’Alberta. Angela Alberga signale avoir reçu les subventions suivantes : bourse Santé du Fonds de recherche du Québec, bourse Accélération du programme MITACS, et bourse d’entrepreneuriat de l’Université Concordia, en dehors des travaux soumis. Jennifer Brown signale avoir reçu un soutien non financier de Novo Nordisk, et des honoraires personnels de Bausch Health, Diététistes du Canada, Obésité Canada et l’Association canadienne des médecins et chirurgiens bariatriques. Yoni Freedhoff est copropriétaire du Bariatric Medical Institute et de Constant Health, qui fournissent des services de gestion du poids; Constant Health a reçu une subvention de Novo Nordisk. Yoni Freedhoff est aussi l’auteur de The diet fix : Why diets fail and how to make them work publié par Crown Publishing Group, et il reçoit des droits d’auteur pour ce livre. Il est également le seul auteur du blogue intitulé Weighty Matters et d’une rubrique pour Medscape et plusieurs autres lettres d’opinion et articles dans lesquels il a exprimé ouvertement ses positions concernant le traitement, la gestion et la prévention de l’obésité. Yoni Freedhoff s’exprime en outre régulièrement au sujet de l’obésité et il reçoit des honoraires et le remboursement de frais de déplacement pour ces activités. Michel Gagner signale avoir reçu des honoraires de conférencier d’Ethicon, WL Gore et Medtronic; des honoraires de consultant de Novo Nordisk, Bausch Health et Lexington Medical; et il détient des options d’achat d’actions de Lexington Medical. Margaret Hahn signale avoir reçu des honoraires de consultation d’Alkermes. Marie-France Langlois signale avoir reçu des honoraires personnels de Novo Nordisk, Valeant, Merck Canada, Sanofi, Eli Lilly et Boehringer Ingelheim; une subvention de Merck Canada et d’autres honoraires d’AstraZeneca et du groupe d’étude TIMI (Thrombolysis in Myocardial Infarction) pour la recherche clinique sur le diabète à titre de chercheuse principale, tous en dehors des travaux soumis. David Macklin signale avoir reçu des honoraires personnels de Novo Nordisk et Bausch Health, en dehors des travaux soumis. Priya Manjoo signale avoir reçu des honoraires personnels de Novo Nordisk, Bausch Health et Sanofi; et des subventions de Boehringer Ingelheim, Sanofi et AstraZeneca, en dehors des travaux soumis. Marie-Philippe Morin signale avoir reçu des honoraires de conférencière de Novo Nordisk, Bausch Health, Eli Lilly, Boehringer Ingelheim, Nestlé Health Science, Janssen et AstraZeneca; une subvention de recherche de Novo Nordisk et Sanofi; et des honoraires de consultante de Novo Nordisk, Bausch Health, Eli Lilly, Boehringer Ingelheim, Janssen et AstraZeneca. Sue Pedersen signale avoir reçu des honoraires personnels de Novo Nordisk, Bausch Health, Janssen, Eli Lilly, Merck, AstraZeneca, Boehringer Ingelheim, Sanofi et Pfizer; des subventions d’Eli Lilly, AstraZeneca, Boehringer Ingelheim et Sanofi; et un soutien non financier de Novo Nordisk, Bausch Health, Janssen, Eli Lilly, AstraZeneca, Boehringer Ingelheim et Sanofi, en dehors des travaux soumis. Megha Poddar signale avoir reçu des honoraires pour de la formation médicale continue (FMC) de Novo Nordisk, Bausch Health, Boehringer Ingelheim, Eli Lilly, Jenssen, Merck, du Canadian Collaborative Research Network et d’Antibody Network; des subventions à la formation de Novo Nordisk et Bausch Health; des honoraires de mentorat de Novo Nordisk; des honoraires de participation à des comités consultatifs de Novo Nordisk et Bausch Health; et une bourse pour un projet d’amélioration de la qualité de Boehringer Ingelheim. Paul Poirier signale avoir reçu des honoraires de consultation et de formation médicale continue d’AstraZeneca, Boehringer Ingelheim, Janssen, Eli Lilly, Novo Nordisk, Valeant et Bausch Health, en dehors des travaux soumis. Judy Shiau signale avoir reçu des honoraires personnels de Novo Nordisk de Bausch Health, en dehors des travaux soumis. Diana Sherifali signale avoir reçu des honoraires de consultante pour son avis sur la gestion de la maladie chronique et du diabète de Merck, et une subvention d’Obésité Canada pour soutenir le processus de revue de la documentation durant la conduite de l’étude. John Sievenpiper signale avoir reçu des subventions des IRSC, du Nutrition Trialists Fund de l’Université de Toronto, de l’International Nut and Dried Fruit Council Foundation, du Tate and Lyle Nutritional Research Fund de l’Université de Toronto, de l’American Society for Nutrition, du Glycemic Control and Cardiovascular Disease in Type 2 Diabetes Fund de l’Université de Toronto, de la National Dried Fruit Trade Association, une bourse d’application des connaissances de la Fondation PSI Graham Farquharson, la bourse du clinicien-chercheur de Diabète Canada, la bourse du jeune chercheur Sun Life Financial Banting & Best Diabetes Centre, une bourse de la Fondation canadienne pour l’innovation et la bourse du Fonds ontarien de recherche du ministère de la Recherche et de l’Innovation de l’Ontario. Le Dr Sievenpiper a reçu des honoraires personnels des entités suivantes : Perkins Coie LLP, Tate & Lyle, Producteurs laitiers du Canada, PepsiCo, FoodMinds LLC, European Fruit Juice Association, International Sweeteners Association, Nestlé Health Science, Société canadienne d’endocrinologie et métabolisme, GI Foundation, Pulse Canada, Wirtschaftliche Vereinigung Zucker e.V., Abbott, Biofortis, Autorité européenne de sécurité des aliments, Physicians Committee for Responsible Medicine, Soy Nutrition Institute, Comité européen des fabricants de sucre. Le Dr Sievenpiper a reçu un soutien non financier de Tate & Lyle, PepsiCo, FoodMinds LLC, European Fruit Juice Association, International Sweeteners Association, Nestlé Health Science, Wirtschaftliche Vereinigung Zucker e.V., Abbott, Biofortis, Autorité européenne de sécurité des aliments, Physicians Committee for Responsible Medicine, Kellogg Canada, American Peanut Council, Barilla, Unilever, Unico Primo, Compagnies Loblaw, WhiteWave Foods, Quaker, California Walnut Commission, Almond Board of California, en dehors des travaux soumis. Le Dr Sievenpiper est membre de l’International Carbohydrate Quality Consortium et des comités d’experts en pratique clinique pour la rédaction des lignes directrices de Diabète Canada, European Association for the Study of Diabetes, Société canadienne de cardiologie et d’Obésité Canada, et il occupe les postes de membre de l’exécutif du Groupe d’étude sur le diabète et la nutrition de l’European Association for the Study of Diabetes et de directeur de la Toronto 3D Knowledge Synthesis and Clinical Trials Foundation. Il est aussi conseiller scientifique non rémunéré pour le programme de sécurité alimentaire, nutrition et réglementation et le comité sur les glucides de l’International Life Science Institute en Amérique du Nord. Il est en relation conjugale avec une personne qui travaille pour Anheuser-Busch InBev. Sanjeev Sockalingam signale avoir reçu des honoraires de Bausch Health Canada au cours des 36 derniers mois. Valerie Taylor signale avoir reçu des honoraires de conférencière de Sunovion. Shahebina Walji signale avoir reçu des honoraires de consultation ou de participation à des comités consultatifs pour Novo Nordisk, Bausch Health et Takeda et des honoraires de conférencière de Novo Nordisk et Bausch Health. Shahebina Walji signale aussi avoir vendu les substituts de repas Optifast à partir d’un centre de gestion du poids. Optifast est un produit fabriqué et vendu par Nestlé. Aucun autre intérêt concurrent n’a été déclaré.

Competing Interests: Competing interests: Sean Wharton reports receiving honoraria and travel expenses and has participated in academic advisory boards for Novo Nordisk, Bausch Health, Eli Lilly and Janssen. Sean Wharton is also the medical director of a medical clinic specializing in weight management and diabetes. David Lau reports receiving grants and research support from AstraZeneca, Novo Nordisk and the Canadian Institutes of Health Research (CIHR); speaker bureau fees from AstraZeneca, Bausch Health, Boehringer Ingelheim, Diabetes Canada, Eli Lilly, Merck and Novo Nordisk; and consulting fees from Amgen, AstraZeneca, Bausch Health, Boehringer Ingelheim, Gilead, HLS Therapeutics, Janssen, Eli Lilly and Novo Nordisk. Michael Vallis is a member of advisory boards for Novo Nordisk, Bausch Health and LifeScan. Michael Vallis has also received consulting fees from Bausch Health, LifeScan, Novo Nordisk and Sanofi, and speaking fees from Novo Nordisk, Sanofi, Bausch Health, Abbott and AbbVie. Arya Sharma reports receiving speaker’s bureau and consulting fees from Novo Nordisk, Bausch Pharmaceuticals and Astra-Zeneca. Laurent Biertho reports receiving grants from Johnson and Johnson and Medtronic, and is a member of advisory boards for Novo Nordisk and Bausch Health, outside the submitted work. Denise Campbell-Scherer has no personal financial relationships, but reports receiving research funding from the following sources in the past 3 years: Novo Nordisk Alberta Diabetes Fund (NOVAD), a peer-reviewed grant that is a partnership between the University Hospital Foundation, Novo Nordisk and Alberta Innovates joint funders; Alberta Innovates Health Solutions (Cancer Prevention Research Opportunity and Collaborative Research and Innovation Opportunities competitions), CIHR (Strategy for Patient-Oriented Research and Knowledge-to-Action competitions); Northern Alberta Family Medicine Fund; and the Alberta Cancer Prevention and Legacy Fund. She also reports receiving knowledge transfer funding from the following sources in the past 3 years: an unrestricted education grant from Obesity Canada, funded by Novo Nordisk Global; a Worldwide University Network Meeting Grant; an Agency for Healthcare Research and Quality R13 grant for a Healthcare Effectiveness and Outcomes Research; and a Physician Learning Program grant from Alberta Health and the Alberta Medical Association. Angela Alberga reports receiving the following grants: the Santé Award from Fonds de Recherche du Quebec, the Mitacs Accelerate Grant, and the Concordia University Start-up Team Grant, outside the submitted work. Jennifer Brown reports receiving nonfinancial support from Novo Nordisk, and personal fees from Bausch Health, Dietitians of Canada, Obesity Canada and the Canadian Association of Bariatric Physicians & Surgeons. Yoni Freedhoff is the co-owner of the Bariatric Medical Institute and Constant Health, which provide weight management services; Constant Health has received a grant from Novo Nordisk. Yoni Freedhoff is also the author of The Diet Fix: Why Diets Fail and How to Make Yours Work published by Crown Publishing Group, and receives royalties for the book. In addition, he is the sole author of the Weighty Matters blog and a column for Medscape and many other op-eds and articles in which he has publicly expressed opinions about the treatment, management and prevention of obesity. Yoni Freedhoff also regularly speaks on topics related to obesity and receives honoraria and travel costs and expenses for same. Michel Gagner reports receiving speaker honoraria from Ethicon, WL Gore and Medtronic; consulting fees from Novo Nordisk, Bausch Health and Lexington Medical; and holds stock options with Lexington Medical. Margaret Hahn reports receiving consulting fees from Alkermes. Marie-France Langlois reports receiving personal fees from Novo Nordisk, Valeant, Merck Canada, Sanofi, Eli Lilly and Boehringer Ingelheim; a grant from Merck Canada; and other fees from AstraZeneca and from TIMI (Thrombolysis in Myocardial Infarction) Study Group for diabetes clinical research as a principal investigator, all outside the submitted work. David Macklin reports receiving personal fees from Novo Nordisk and Bausch Health, outside the submitted work. Priya Manjoo reports receiving personal fees from Novo Nordisk, Bausch Health and Sanofi; and grants from Boehringer Ingelheim, Sanofi and AstraZeneca, outside the submitted work. Marie-Philippe Morin reports receiving speaker honoraria from Novo Nordisk, Bausch Health, Eli Lilly, Boehringer Ingelheim, Nestlé Health Science, Janssen and AstraZeneca; research subvention from Novo Nordisk and Sanofi; and consultation honoraria from Novo Nordisk, Bausch Health, Eli Lilly, Boehringer Ingelheim, Janssen and AstraZeneca. Sue Pedersen reports receiving personal fees from Novo Nordisk, Bausch Health, Janssen, Eli Lilly, Merck, AstraZeneca, Boehringer Ingelheim, Sanofi, Pfizer; grants from Eli Lilly, AstraZeneca, Boehringer Ingelheim and Sanofi; and nonfinancial support from Novo Nordisk, Bausch Health, Janssen, Eli Lilly, AstraZeneca, Boehringer Ingelheim and Sanofi, outside the submitted work. Megha Poddar reports receiving honoraria for continuing medical education (CME) from Novo Nordisk, Bausch Health, Boehringer Ingelheim, Eli Lilly, Jenssen, Merck, the Canadian Collaborative Research Network and the Antibody Network; education grants from Novo Nordisk and Bausch Health; fees for mentorship from Novo Nordisk; fees for membership of advisory boards from Novo Nordisk and Bausch Health; and a quality improvement project grant from Boehringer Ingelheim. Paul Poirier reports receiving fees for consulting and continuing medical education from AstraZeneca, Boehringer Ingelheim, Janssen, Eli Lilly, Novo Nordisk, Valeant and Bausch Health, outside the submitted work. Judy Shiau reports receiving personal fees from Novo Nordisk and Bausch Health, outside the submitted work. Diana Sherifali reports receiving consulting fees for advice regarding chronic disease and diabetes management from Merck, and a grant from Obesity Canada to support the literature review process, during the conduct of the study. John Sievenpiper reports receiving grants from CIHR, the Nutrition Trialists Fund at the University of Toronto, the International Nut and Dried Fruit Council Foundation, the Tate & Lyle Nutritional Research Fund at the University of Toronto, the American Society for Nutrition, the Glycemic Control and Cardiovascular Disease in Type 2 Diabetes Fund at the University of Toronto, the National Dried Fruit Trade Association, PSI Graham Farquharson Knowledge Translation Fellowship, the Diabetes Canada Clinician Scientist award, the Banting & Best Diabetes Centre Sun Life Financial New Investigator Award, the Canada Foundation for Innovation, and the Ministry of Research and Innovation’s Ontario Research Fund. Dr. Sievenpiper has received personal fees from Perkins Coie LLP, Tate & Lyle, Dairy Farmers of Canada, PepsiCo, Food-Minds LLC, European Fruit Juice Association, International Sweeteners Association, Nestlé Health Science, Canadian Society for Endocrinology and Metabolism, GI Foundation, Pulse Canada, Wirtschaftliche Vereinigung Zucker e.V., Abbott, Biofortis, the European Food Safety Authority, the Physicians Committee for Responsible Medicine, the Soy Nutrition Institute and the Comité Européen des Fabricants de Sucre. Dr. Sievenpiper has received nonfinancial support from Tate & Lyle, PepsiCo, FoodMinds LLC, European Fruit Juice Association, International Sweeteners Association, Nestlé Health Science, Wirtschaftliche Vereinigung Zucker e.V., Abbott, Biofortis, the European Food Safety Authority and the Physicians Committee for Responsible Medicine, Kellogg Canada, American Peanut Council, Barilla, Unilever, Unico Primo, Loblaw Companies, WhiteWave Foods, Quaker, California Walnut Commission, Almond Board of California, outside the submitted work. Dr. Sievenpiper is a member of the International Carbohydrate Quality Consortium and the Clinical Practice Guidelines Expert Committees of Diabetes Canada, European Association for the Study of Diabetes, Canadian Cardiovascular Society, and Obesity Canada, and holds appointments as an Executive Board Member of the Diabetes and Nutrition Study Group of the European Association for the Study of Diabetes, and as Director of the Toronto 3D Knowledge Synthesis and Clinical Trials Foundation. He is also an unpaid scientific adviser for the Program in Food Safety, Nutrition and Regulatory Affairs and the Carbohydrates Committee of the International Life Science Institute North America. He has a spousal relationship with an employee of Anheuser-Busch InBev. Sanjeev Sockalingam reports receiving honoraria from Bausch Health Canada within the last 36 months. Valerie Taylor reports receiving speaker fees from Sunovion. Shahebina Walji reports receiving consulting or advisory board fees from Novo Nordisk, Bausch Health and Takeda and speaker’s bureau fees from Novo Nordisk and Bausch Health. Shahebina Walji also reports selling Optifast Meal replacements through a weight management centre Optifast is a product produced and sold by Nestlé. No other competing interests were declared.

Background: Dyslipidemia is a major risk factor for cardiovascular diseases (CVD). Worldwide, a third of ischemic heart disease is due to abnormal cholesterol levels and it is the most common cause of cardiovascular deaths in Colombia. In Colombia, no representative, large-scale study has assessed the prevalence of dyslipidemia. The aim of the present analysis was to identify the magnitude of the problem in Colombia, a middle-income-country with large regional, geographic, and socio-economical differences., Material and Methods: The sample comprised 6628 individuals aged 35 to 70 years (mean age 50.7 years, 64.1% women) residing in the four Colombian regions., Results: The overall prevalence of dyslipidemia was 87.7% and was substantially higher among participants older than 50 years, male, rural residents, and those with a lower level of education (66.8%), and with a lower income (66.4%). High non HDL-c was the most common abnormality (75.3%). The values of total cholesterol and non-HDL-cholesterol were higher in areas with the lowest health needs index than in the areas with intermediate and highest health need index, the isolated HDL-c value was much lower., Conclusion: Colombia has a high prevalence of abnormalities of the lipid profile. The causes of the high rates of dyslipidemia were not well define in this study, but were more common in rural and poorer regions and among those with lower socio-economical status. Strategies to tackle the adverse lipid profile to reduce CVD are needed in Colombia, particularly in rural areas and among the areas with the higher health need index., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Understanding the mechanisms regulating recruitment of human skeletal (stromal or mesenchymal) stem cells (hMSC) to sites of tissue injury is a prerequisite for their successful use in cell replacement therapy. Chemokine-like protein TAFA2 is a recently discovered neurokine involved in neuronal cell migration and neurite outgrowth. Here, we demonstrate a possible role for TAFA2 in regulating recruitment of hMSC to bone fracture sites. TAFA2 increased the in vitro trans-well migration and motility of hMSC in a dose-dependent fashion and induced significant morphological changes including formation of lamellipodia as revealed by high-content-image analysis at single-cell level. Mechanistic studies revealed that TAFA2 enhanced hMSC migration through activation of the Rac1-p38 pathway. In addition, TAFA2 enhanced hMSC proliferation, whereas differentiation of hMSC toward osteoblast and adipocyte lineages was not altered. in vivo studies demonstrated transient upregulation of TAFA2 gene expression during the inflammatory phase of fracture healing in a closed femoral fracture model in mice, and a similar pattern was observed in serum levels of TAFA2 in patients after hip fracture. Finally, interleukin-1β was found as an upstream regulator of TAFA2 expression. Our findings demonstrate that TAFA2 enhances hMSC migration and recruitment and thus is relevant for regenerative medicine applications. Stem Cells 2019;37:407-416., (© 2018 The Authors. Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press 2018.)

Symmetry effects in internal conversion are studied by means of two isomeric cyclic tertiary aliphatic amines in a velocity map imaging (VMI) experiment on the femtosecond timescale. It is demonstrated that there is a delicate structural dependence on when coherence is preserved after the transition between the 3p and 3s Rydberg states. N-Methyl morpholine (NMM) shows unambiguous preserved coherence, consistent with previous work, which is decidedly switched off by the repositioning of oxygen within the ring. From the differences in these dynamics, and an examination of the potential energy surface following the normal modes of vibration, it becomes clear that there is a striking dependence on atom substitution, which manifests itself in the permitted modes of vibration that take the system out of the Franck-Condon region through to the 3s minimum. It is shown that the non Fermi-like behaviour of NMM is due to a conical intersection (CI) between the 3px and 3s states lying directly along the symmetry allowed path of steepest descent out of the Franck-Condon region. NMI, where the symmetry has been changed, is shown to undergo internal conversion in a more Fermi-like manner as the energy spreads through the available modes ergodically.

Alzheimer's disease (AD) is the most frequent neurodegenerative disease amongst the elderly. The SNPs rs429358 and rs7412 in the APOE gene are the most common risk factor for sporadic AD, and there are three different alleles commonly referred to as APOE-ε2, APOE-ε3 and APOE-ε4. Induced pluripotent stem cells (iPSCs) hold great promise to model AD as such cells can be differentiated in vitro to the required cell type. Here we report the use of CRISPR/Cas9 technology employed on iPSCs from a healthy individual with an APOE-ε3/ε4 genotype to obtain isogenic APOE-ε2/ε2, APOE-ε3/ε3, APOE-ε4/ε4 lines as well as an APOE-knock-out line., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

We investigate the ultrafast photoinduced dynamics of the cyclic disulfide 1,2-dithiane upon 200 nm excitation by time-resolved photoelectron spectroscopy and show that the S-S bond breaks on an ultrafast time scale. This stands in stark contrast to excitation at longer wavelengths where the initially excited S 1 state evolves as the wavepacket is guided towards a conical intersection with S 0 by a torsional motion involving a partially broken bond between the sulfur atoms. This process at lower excitation energy allows for efficient (re-)population of S 0 , rendering dithiane intact. At 200 nm, in contrast, the excitation leads to a manifold of higher excited states, S n , that are primarily of Rydberg character. We are able to follow the gradual transition from the initially excited state to the dissociative receiver state in real time. The Rydberg states are intersected by a repulsive valence state that mediates a transition to the repulsive S 2 surface. Therefore, we propose that the resulting diradical will eventually break apart on a longer timescale. The findings imply that upon going from UV-B to UV-C light the structural integrity of the disulfide moiety is compromised and proteins irradiated in this range will not be able to reform the initial tertiary structure, leading to loss of function., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Hematopoietic stem cell transplantation often involves the cryopreservation of stem cell products. Currently, the standard cryoprotective agent (CPA) is dimethyl sulfoxide (DMSO), which is known to cause concentration-related toxicity and side effects when administered to patients. Based on promising in vitro data from our previous study using pentaisomaltose (a 1 kDa subfraction of Dextran 1) as an alternative to DMSO for cryopreservation of hematopoietic progenitor cells (HPCs) from apheresis products, we proceeded to a preclinical model and compared the two CPAs with respect to engraftment of human hematopoietic stem and progenitor cells (HSPCs) in the immunodeficient NSG mouse model. Human HPCs from apheresis products were cryopreserved with either pentaisomaltose or DMSO, and the following outcomes were measured: (1) the post-thaw recovery of cryopreserved cells and clonogenic potential of CD34 + cells and (2) hematopoietic engraftment in NSG mice. We found that recovery and colony-forming cells data were comparable between pentaisomaltose and DMSO. The engraftment data revealed comparable human CD45 + levels in peripheral blood at 8 weeks and bone marrow at 16 weeks post transplantation. Additionally, the frequencies of CD34 + CD38 low/negative and myeloid/lymphoid cells in the bone marrow were comparable. We here demonstrated that long-term engrafting HSPCs were well preserved in pentaisomaltose and comparable to cells cryopreserved with DMSO. Although a clinical trial is necessary to translate these results into human use, the present data represent an important step toward the replacement of DMSO with a non-toxic alternative.

The simplification of fixed dose medications by using a single 'polypill' is an attractive strategy to improve adherence to medications which has shown benefit to cardiovascular risk factor control and cardiovascular disease prevention or delay in the progression of these diseases. We review the evidence obtained from a series of clinical trials demonstrating an improvement in adherence to the polypill compared to the use of each compound separately, and found similar or better control of the classical cardiovascular risk factors and a similar safety profile. These results suggest that the use of the polypill could have a beneficial impact in cardiovascular morbidity and mortality. Furthermore, the polypill has the potential to improve cost effectiveness and is simple to use. However, before recommending the implementation of the polypill in programs aimed at primary and secondary cardiovascular prevention, we are awaiting the results of several current clinical trials aimed at measuring the impact on the frequency of major cardiovascular outcomes, particularly in low-medium-income countries.

The derivation of functional cardiomyocytes (CMs) from human embryonic stem cells (hESCs) represents a unique way of studying human cardiogenesis, including the development of CM subtypes. In this study, we investigated the development and organization of hESC-derived cardiomyocytes (hESC-CMs) and examined how the expression levels of CM subtypes correspond to human in vivo cardiogenesis. Beating clusters were used to determine cardiac differentiation, which was evaluated by the expression of cardiac genes GATA4 and TNNT2 and subcellular localization of GATA4 and NKX2.5. Sharp electrode recordings to determine action potentials (APs) further revealed spatial organization of intracluster CM subtypes (ie, complex clusters). Nodal-, atrial-, and ventricular-like AP morphologies were detected within distinct regions of complex clusters. The ability of different CM subtypes to self-organize was documented by immunohistochemical analyses and a differential spatial expression of β-III tubulin, myosin light chain 2v (MLC-2V), and α-smooth muscle actin (α-SMA). Furthermore, all hESC-CM subtypes formed expressed primary cilia, which are known to coordinate cellular signaling pathways during cardiomyogenesis and heart development. This study expands the foundation for studying regulatory pathways for spatial and temporal CM differentiation during human cardiogenesis.

A fast track "Hot Start" process was implemented to launch the European Bank for Induced Pluripotent Stem Cells (EBiSC) to provide early release of a range of established control and disease linked human induced pluripotent stem cell (hiPSC) lines. Established practice amongst consortium members was surveyed to arrive at harmonised and publically accessible Standard Operations Procedures (SOPs) for tissue procurement, bio-sample tracking, iPSC expansion, cryopreservation, qualification and distribution to the research community. These were implemented to create a quality managed foundational collection of lines and associated data made available for distribution. Here we report on the successful outcome of this experience and work flow for banking and facilitating access to an otherwise disparate European resource, with lessons to benefit the international research community. ETOC: The report focuses on the EBiSC experience of rapidly establishing an operational capacity to procure, bank and distribute a foundational collection of established hiPSC lines. It validates the feasibility and defines the challenges of harnessing and integrating the capability and productivity of centres across Europe using commonly available resources currently in the field., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

The truncated mutant form of the charged multivesicular body protein 2B (CHMP2B) is causative for frontotemporal dementia linked to chromosome 3 (FTD3). CHMP2B is a constituent of the endosomal sorting complex required for transport (ESCRT) and, when mutated, disrupts endosome-to-lysosome trafficking and substrate degradation. To understand the underlying molecular pathology, FTD3 patient induced pluripotent stem cells (iPSCs) were differentiated into forebrain-type cortical neurons. FTD3 neurons exhibited abnormal endosomes, as previously shown in patients. Moreover, mitochondria of FTD3 neurons displayed defective cristae formation, accompanied by deficiencies in mitochondrial respiration and increased levels of reactive oxygen. In addition, we provide evidence for perturbed iron homeostasis, presenting an in vitro patient-specific model to study the effects of iron accumulation in neurodegenerative diseases. All phenotypes observed in FTD3 neurons were rescued in CRISPR/Cas9-edited isogenic controls. These findings illustrate the relevance of our patient-specific in vitro models and open up possibilities for drug target development., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Chlorophenols are highly toxic, environmentally-persistent compounds which have been classified as probable human carcinogens by the United States Environmental Protection Agency. Due to the high toxicity of these compounds, it is necessary to treat water and soils with concentrations of chlorophenols above the detection limit set by regulatory agencies. The aim of this work is to demonstrate the capabilities of using ball-milled magnesium for the dechlorination of PCP. Comparison of dechlorination processes were performed in an attempt to determine the most effective system for degradation of PCP to phenol. Three systems with powerful capabilities of treatment were studied: ball-milled zero-valent magnesium (ZVMg), ball-milled zero-valent magnesium carbon (ZVMg/C), and ball-milled zero-valent magnesium with palladium (ZVMg/Pd). In addition to measuring PCP disappearance, all byproducts were identified and quantified for each degradation system. The results of these studies indicate that all three of the systems degrade PCP within 30 min. The most rapid and complete PCP dechlorination is achieved using ball-milled Mg/Pd and a matrix consisting of at least 0.02 g Mg0/mL ethanol, and 10 μL acetic acid/mL ethanol, in which case 20 ng/μL of PCP was dechlorinated to chlorophenols in approximately 15 min with complete dechlorination achieved in six days. Carbon mass balances of 90.16% for Mg, 94.76% (Mg/C) and 97.05% (Mg/Pd) verify dechlorination was responsible for declining concentrations of PCP. The reactions of PCP degradation and phenol formation were found to follow pseudo-first order kinetics for all systems. Further work will consist of optimization and development of field-scale applications., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Frontotemporal dementia with parkinsonism linked to chromosome 17q21.2 (FTDP-17) is an autosomal-dominant neurodegenerative disorder. Mutations in the gene coding the microtubule-associated protein tau (MAPT) can cause FTDP-17 but the underlying mechanisms of the disease are still unknown. Induced pluripotent stem cells (iPSCs) hold great promise to model FTDP-17 as such cells can be differentiated in vitro to the required neuronal cell type. Here, we report the generation of iPSCs from a 44-year-old symptomatic woman carrying a S305I mutation in the MAPT-gene., (Copyright © 2016 Michael Boutros, German Cancer Research Center, Heidelberg, Germany. Published by Elsevier B.V. All rights reserved.)

Frontotemporal dementia with parkinsonism linked to chromosome 17q21.2 (FTDP-17) is an autosomal-dominant neurodegenerative disorder. Mutations in the MAPT (microtubule-associated protein tau) gene can cause FTDP-17, but the underlying pathomechanisms of the disease are still unknown. Induced pluripotent stem cells (iPSCs) hold great promise to model FTDP-17 as such cells can be differentiated in vitro to the required cell type. Furthermore, gene-editing approaches allow generating isogenic gene-corrected controls that can be used as a very specific control. Here, we report the generation of genetically corrected iPSCs from a pre-symptomatic carrier of the R406W mutation in the MAPT-gene., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Induced pluripotent stem cells (iPSCs) hold great promise to model diseases, where the disease affected cell type is difficult to access. A major obstacle for the development of disease models is the lack of well characterized control iPSCs from old people not affected by such a disease. Furthermore, gene-editing approaches often require iPSCs from healthy donors, where pathogenic mutations can be inserted if patient material is not available. Here, we report the generation of an iPSC line (16423 #6) from a 77-year-old woman, who did not display any disease symptoms at the time, when the skin biopsy was taken., (Copyright © 2016 Michael Boutros, German Cancer Research Center, Heidelberg, Germany. Published by Elsevier B.V. All rights reserved.)

Frontotemporal dementia with parkinsonism linked to chromosome 17q21.2 (FTDP-17) is an autosomal-dominant neurodegenerative disorder. Mutations in the MAPT (microtubule-associated protein tau) gene can cause FTDP-17, but the underlying pathomechanisms of the disease are still unknown. Induced pluripotent stem cells (iPSCs) hold great promise to model FTDP-17 as such cells can be differentiated in vitro to the required cell type. Furthermore, gene-editing approaches allow generating isogenic gene-corrected controls that can be used as a very specific control. Here, we report the generation of genetically corrected iPSCs from a 59-year-old female FTD-17 patient carrying an R406W mutation in the MAPT-gene., (Copyright © 2016 Michael Boutros, German Cancer Research Center, Heidelberg, Germany. Published by Elsevier B.V. All rights reserved.)

Frontotemporal dementia with parkinsonism linked to chromosome 17q21.2 (FTDP-17) is an autosomal-dominant neurodegenerative disorder. Mutations in the MAPT (microtubule-associated protein tau)-gene can cause FTDP-17, but the underlying pathomechanisms of the disease are still unknown. Induced pluripotent stem cells (iPSCs) hold great promise to model FTDP-17 as such cells can be differentiated in vitro to the required cell type. Furthermore, gene-editing approaches allow generating isogenic gene-corrected controls that can be used as a very specific control. Here, we report the generation of genetically corrected iPSCs from a 57-year-old female FTD-17 patient carrying an P301L mutation in the MAPT-gene., (Copyright © 2016 Michael Boutros, German Cancer Research Center, Heidelberg, Germany. Published by Elsevier B.V. All rights reserved.)

Background: Bariatric surgery in Canada is primarily delivered within publicly funded specialty clinics. Previous studies have demonstrated that bariatric surgery is superior to intensive medical management for reduction of weight and obesity-related comorbidities. Our objective was to compare the effectiveness and safety of laparoscopic Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (LSG) and adjustable gastric banding (LAGB) in a publicly funded, population-based bariatric treatment program., Methods: We followed consecutive bariatric surgery patients for 2 years. The primary outcome was weight change (in kilograms). Between-group changes were analyzed using multivariable regression. Last-observation-carried-forward imputation was used for missing data., Results: We included 150 consecutive patients (51 RYGB; 51 LSG; 48 LAGB) in our study. At baseline, mean age was 43.5 ± 9.5 years, 87.3% of patients were women, and preoperative body mass index (BMI) was 46.2 ± 7.4. Absolute and relative (% of baseline) weight loss at 2 years were 36.6 ± 19.5 kg (26.1 ± 12.2%) for RYGB, 21.4 ± 16.0 kg (16.4 ± 11.6%) for LSG and 7.0 ± 9.7 kg (5.8 ± 7.9%) for LAGB (p < 0.001). Change in BMI was greater for the RYGB (-13.0 ± 6.6) than both the LSG (-7.6 ± 5.7) and the LAGB (-2.6 ± 3.5) groups (p < 0.001). The reduction in diabetes, hypertension and dyslipidemia was greater after RYGB than after LAGB (all p < 0.05). There were no deaths. The anastomotic and staple leakage rate was 1.3%., Conclusion: In a publicly funded, population-based bariatric surgery program, RYGB and LSG demonstrated greater weight loss than the LAGB procedure. Bypass resulted in the greatest reduction in obesity-related comorbidities. All procedures were safe.

Frontotemporal dementia (FTD) is an early onset neurodegenerative disease. Mutations in several genes cause familial FTD and one of them is charged multivesicular body protein 2B (CHMP2B) on chromosome 3 (FTD3), a component of the endosomal sorting complex required for transport III (ESCRT-III). We have generated an induced pluripotent stem cell (iPSC) line of a healthy individual and inserted the CHMP2B IVS5AS G-C gene mutation into both alleles, resulting in aberrant splicing. This human iPSC line provides an ideal model to study CHMP2B-dependent phenotypes of FTD3., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Frontotemporal dementia (FTD) is an early onset neurodegenerative disease. Mutations in several genes cause familial FTD and one of them is charged multivesicular body protein 2B (CHMP2B) on chromosome 3 (FTD3), a component of the endosomal sorting complex required for transport III (ESCRT-III). We have generated an induced pluripotent stem cell (iPSC) line of a healthy individual and inserted the CHMP2B IVS5AS G-C gene mutation into one of the alleles, resulting in aberrant splicing. This human iPSC line provides an ideal model to study CHMP2B-dependent phenotypes of FTD3., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Cryopreserved hematopoietic stem cell products are widely used for certain hematologic malignancies. Dimethyl sulfoxide (DMSO) is the most widely used cryoprotective agent (CPA) today, but due to indications of cellular toxicity, changes of the cellular epigenetic state, and patient-related side effects, there is an increasing demand for DMSO-free alternatives. We therefore investigated whether Pentaisomaltose (PIM), a low-molecular-weight carbohydrate (1 kDa), can be used for cryopreservation of peripheral blood stem cells, more specifically hematopoietic progenitor cell apheresis (HPC(A)) product., Study Design and Methods: We cryopreserved patient or donor HPC(A) products using 10% DMSO or 16% PIM and quantified the recovery of CD34+ cells and CD34+ subpopulations by multicolor flow cytometry. In addition, we compared the frequency of HPCs after DMSO and PIM cryopreservation using the colony-forming cells (CFCs) assay., Results: The mean CD34+ cell recovery was 56.3 ± 23.7% (11.4%-97.3%) and 58.2 ± 10.0% (45.7%-76.9%) for 10% DMSO and 16% PIM, respectively. The distribution of CD34+ cell subpopulations was similar when comparing DMSO or PIM as CPA. CFC assay showed mean colony numbers of 70.7 ± 25.4 (range, 37.8-115.5) and 67.7 ± 15.7 (range, 48-86) for 10% DMSO and 16% PIM, respectively., Conclusion: Our findings demonstrate that PIM cryopreservation of HPC(A) products provides recovery of CD34+ cells, CD34+ subpopulations, and CFCs similar to that of DMSO cryopreservation and therefore may have the potential to be used for cryopreservation of peripheral blood stem cells., (© 2016 The Authors Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.)

Induced pluripotent stem cells (iPSCs) were generated from skin fibroblasts isolated from a 58-year old male with a L150P mutation in the presenilin 1 (PSEN-1) gene, which is responsible for the majority of familial cases of Alzheimer's disease (AD). The iPSCs were established by co-electroporation with episomal plasmids containing hOCT4, hSOX2, hL-MYC, hKLF4, hNANOG, hLIN28, and short hairpin RNA against TP53. The iPSCs contained the specific heterozygous mutation c.449C>T, had normal karyotype, expressed the expected pluripotency genes and displayed in vitro differentiation potential to the three germ layers. The iPSCs may be useful for studying familial AD pathology in vitro., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Skin fibroblasts were obtained from a 59-year-old woman diagnosed with frontotemporal dementia. The disease is caused by a R406W mutation in microtubule-associated protein tau (MAPT). Induced pluripotent stem cells (iPSCs) were established by electroporation with episomal plasmids containing hOCT4, hSOX2, hKLF2, hL-MYC, hLIN-28 and shP53. iPSCs were free of genomically integrated reprogramming genes, contained the expected c.1216C>T substitution in exon 13 of the MAPT gene, expressed the expected pluripotency markers, displayed in vitro differentiation potential to the three germ layers and had normal karyotype. The iPSC line may be useful for studying hereditary frontotemporal dementia and TAU pathology in vitro., (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)

Skin fibroblasts were obtained from a 57-year-old woman diagnosed with frontotemporal dementia. The disease is caused by a P301L mutation in microtubule-associated protein tau (MAPT). Induced pluripotent stem cells (iPSCs) were established by electroporation with episomal plasmids containing hOCT4, hSOX2, hKLF2, hL-MYC, hLIN-28 and shP53. iPSCs were free of genomically integrated reprogramming genes, contained the expected c.902C>T substitution in exon 10 of the MAPT gene, expressed the expected pluripotency markers, displayed in vitro differentiation potential to the three germ layers and had normal karyotype. The iPSC line may be useful for studying hereditary frontotemporal dementia and TAU pathology in vitro., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Skin fibroblasts were obtained from a 28-year-old pre-symptomatic woman carrying a R406W mutation in microtubule-associated protein tau (MAPT), known to cause frontotemporal dementia. Induced pluripotent stem cell (iPSCs) were established by electroporation with episomal plasmids containing hOCT4, hSOX2, hKLF2, hL-MYC, hLIN-28 and shP53. iPSCs were free of genomically integrated reprogramming genes, contained the expected c.1216C>T substitution in exon 13 of the MAPT gene, expressed the expected pluripotency markers, displayed in vitro differentiation potential to the three germ layers and had normal karyotype. The iPSC line may be useful for studying hereditary frontotemporal dementia and TAU pathology in vitro., (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)

Restricted by federal regulations and limited remediation options, buildings contaminated with paint laden with polychlorinated biphenyls (PCBs) have high costs associated with the disposal of hazardous materials. As opposed to current remediation methods which are often destructive and a risk to the surrounding environment, this study suggests a non-metal treatment system (NMTS) and a bimetallic treatment system (BTS) as versatile remediation options for painted industrial structures including concrete buildings, and metal machine parts. In this field study, four areas of a discontinued Department of Defense site were treated and monitored over 3 weeks. PCB levels in paint and treatment system samples were analyzed through gas chromatography/electron capture detection (GC-ECD). PCB concentrations were reduced by 95 percent on painted concrete and by 60-97 percent on painted metal with the majority of the PCB removal occurring within the first week of application. Post treatment laboratory studies including the utilization of an activated metal treatment system (AMTS) further degraded PCBs in BTS and NMTS by up to 82 percent and 99 percent, respectively, indicating that a two-step remediation option is viable. These findings demonstrate that the NMTS and BTS can be an effective, nondestructive, remediation process for large painted structures, allowing for the reuse or sale of remediated materials that otherwise may have been disposed., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Low socioeconomic status (SES) has been associated with higher risk of cardiometabolic diseases in developed societies, but investigation of SES and cardiometabolic risk in children in less economically developed populations is sparse. We aimed to examine associations among SES and cardiometabolic risk factors in Colombian children., Methods: We used data from a population-based study of 1282 children aged 6-10 years from Bucaramanga, Colombia. SES was classified according to household wealth, living conditions and access to public utilities. Anthropometric and biochemical parameters were measured at a clinic visit. Cardiometabolic risk factors were analysed continuously using linear regression and as binary outcomes-according to established paediatric cut points-using logistic regression to calculate OR and 95% CIs., Results: Mean age of the children was 8.4 (SD 1.4) and 51.1% of the sample were boys. Odds of overweight/obesity, abdominal obesity and insulin resistance were greater among higher SES. Compared with the lowest SES stratum, children in the highest SES had higher odds of overweight/obesity (OR=3.25, 95% CI 1.89 to 5.57), abdominal obesity (OR=2.74, 95% CI 1.41 to 5.31) and insulin resistance (OR=2.60, 95% CI 1.81 to 3.71). In contrast, children in the highest SES had lower odds of hypertriglyceridaemia (triglycerides ≥90th centile; OR=0.28, 95% CI 0.14 to 0.54) and low (≤10th centile) high-density lipoprotein (HDL) cholesterol (OR=0.35, 95% CI 0.15 to 0.78)., Conclusions: In Colombian children, SES is directly associated with obesity and insulin resistance, but inversely associated with dyslipidaemia (hypertriglyceridaemia and low HDL cholesterol). Our findings highlight the need to analyse cardiometabolic risk factors separately in children and to carefully consider a population's level of economic development when studying their social determinants of cardiometabolic disease., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Obesity is a chronic and complex medical condition associated with a large number of complications affecting most organs and systems through multiple pathways. Strategies for weight management include behavioral, pharmacological, and surgical interventions, all of which can result in a reduction in obesity-related comorbidities and improvements in quality of life. However, subsequent weight regain often reduces the durability of these improvements. The objective of this article is to review evidence supporting the long-term effects of intentional weight loss on morbidity, mortality, quality of life, and health-care cost. Overall, considerable evidence suggests that intentional weight loss is associated with clinically relevant benefits for the majority of obesity-related comorbidities. However, the degree of weight loss that must be achieved and sustained to reap these benefits varies widely between comorbidities.

This study evaluates the capability, efficacy and practicality of a combined approach based on solvent extraction and chemical reduction to simultaneously degrade polycyclic aromatic hydrocarbons (PAHs) and their oxygenated derivatives (OPAHs) in spiked soil. The spiked soil was washed using a composite organic solvent consisting of ethanol and ethyl lactate (1:1, v/v) and then degradation of the extracted contaminants using zero-valent magnesium. The extraction conditions were optimized at 25 °C with solvent-soil ratio of 2:1 (v/w) and the ensuing degradation efficiency ranged from 79% to 88% for the OPAHs, and 66% to 87% for the PAHs after 24 h of reaction at pH of 6.1. The reductive degradation of the spiked contaminants followed pseudo-first-order kinetics; however, comparing the kinetic results of this study to soil-free studies, the degradation rates are significantly reduced. It can be inferred that extracted organic or inorganic components from the soil medium hinder the degradation process, possibly by reducing the reactivity of the activated metal. Furthermore, to our understanding, this study is the first report on the simultaneous degradation of these priority pollutants and their oxygenated derivatives. The experimental results encourage the application of this magnesium/co-solvent system for future pilot-scale remediation studies.

Background: Guidelines and experts describe 5% to 10% reductions in body weight as 'clinically important'; however, it is not clear if 5% to 10% weight reductions correspond to clinically important improvements in health-related quality of life (HRQL). Our objective was to calculate the amount of weight loss required to attain established minimal clinically important differences (MCIDs) in HRQL, measured using three validated instruments., Methods: Data from the Alberta Population-based Prospective Evaluation of Quality of Life Outcomes and Economic Impact of Bariatric Surgery (APPLES) study, a population-based, prospective Canadian cohort including 150 wait-listed, 200 medically managed and 150 surgically treated patients were examined. Two-year changes in weight and HRQL measures (Short-Form (SF)-12 physical (PCS; MCID = 5) and mental (MCS; MCID = 5) component summary score, EQ-5D Index (MCID = 0.03) and Visual Analog Scale (VAS; MCID = 10), Impact of Weight on Quality of Life (IWQOL)-Lite total score (MCID = 12)) were calculated. Separate multivariable linear regression models were constructed within medically and surgically treated patients to determine if weight changes achieved HRQL MCIDs. Pooled analysis in all 500 patients was performed to estimate the weight reductions required to achieve the pre-defined MCID for each HRQL instrument., Results: Mean age was 43.7 (SD 9.6) years, 88% were women, 92% were white, and mean initial body mass index was 47.9 (SD 8.1) kg/m2. In surgically treated patients (two-year weight loss = 16%), HRQL MCIDs were reached for all instruments except the SF-12 MCS. In medically managed patients (two-year weight loss = 3%), MCIDs were attained in the EQ-index but not the other instruments. In all patients, percent weight reductions to achieve MCIDs were: 23% (95% confidence interval (CI): 17.5, 32.5) for PCS, 25% (17.5, 40.2) for MCS, 9% (6.2, 15.0) for EQ-Index, 23% (17.3, 36.1) for EQ-VAS, and 17% (14.1, 20.4) for IWQOL-Lite total score., Conclusions: Weight reductions to achieve MCIDs for most HRQL instruments are markedly higher than the conventional threshold of 5% to 10%. Surgical, but not medical treatment, consistently led to clinically important improvements in HRQL over two years., Trial Registration: Clinicaltrials.gov NCT00850356.

The discovery of human-induced pluripotent stem cells (iPSCs) has sparked great interest in the potential treatment of patients with their own in vitro differentiated cells. Recently, knockout of the Tumor Protein 53 (p53) gene was reported to facilitate reprogramming but unfortunately also led to genomic instability. Here, we report that transient suppression of p53 during nonintegrative reprogramming of human fibroblasts leads to a significant increase in expression of pluripotency markers and overall number of iPSC colonies, due to downstream suppression of p21, without affecting apoptosis and DNA damage. Stable iPSC lines generated with or without p53 suppression showed comparable expression of pluripotency markers and methylation patterns, displayed normal karyotypes, contained between 0 and 5 genomic copy number variations and produced functional neurons in vitro. In conclusion, transient p53 suppression increases reprogramming efficiency without affecting genomic stability, rendering the method suitable for in vitro mechanistic studies with the possibility for future clinical translation., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Obesity is a pressing public health concern, which frequently presents in primary care. With the explosive obesity epidemic, there is an urgent need to maximize effective management in primary care. The 5As of Obesity Management™ (5As) are a collection of knowledge tools developed by the Canadian Obesity Network. Low rates of obesity management visits in primary care suggest provider behaviour may be an important variable. The goal of the present study is to increase frequency and quality of obesity management in primary care using the 5As Team (5AsT) intervention to change provider behaviour., Methods/design: The 5AsT trial is a theoretically informed, pragmatic randomized controlled trial with mixed methods evaluation. Clinic-based multidisciplinary teams (RN/NP, mental health, dietitians) will be randomized to control or the 5AsT intervention group, to participate in biweekly learning collaborative sessions supported by internal and external practice facilitation. The learning collaborative content addresses provider-identified barriers to effective obesity management in primary care. Evidence-based shared decision making tools will be co-developed and iteratively tested by practitioners. Evaluation will be informed by the RE-AIM framework. The primary outcome measure, to which participants are blinded, is number of weight management visits/full-time equivalent (FTE) position. Patient-level outcomes will also be assessed, through a longitudinal cohort study of patients from randomized practices. Patient outcomes include clinical (e.g., body mass index [BMI], blood pressure), health-related quality of life (SF-12, EQ5D), and satisfaction with care. Qualitative data collected from providers and patients will be evaluated using thematic analysis to understand the context, implementation and effectiveness of the 5AsT program., Discussion: The 5AsT trial will provide a wide range of insights into current practices, knowledge gaps and barriers that limit obesity management in primary practice. The use of existing resources, collaborative design, practice facilitation, and integrated feedback loops cultivate an applicable, adaptable and sustainable approach to increasing the quantity and quality of weight management visits in primary care., Trial Registration: NCT01967797.

Objective: To characterize health-related quality of life (HRQL) impairment in severely obese subjects, using several validated instruments., Methods: A cross-sectional analysis of 500 severely obese subjects was completed. Short-Form (SF)-12 [Physical (PCS) and Mental (MCS) component summary scores], EuroQol (EQ)-5D [Index and Visual Analog Scale (VAS)], and Impact of Weight on Quality of Life (IWQOL)-Lite were administered. Multivariable linear regression models were performed to identify independent predictors of HRQL., Results: Increasing BMI was associated with lower PCS (-1.33 points per 5 kg/m(2) heavier; P < 0.001), EQ-index (-0.02; P < 0.001), EQ-VAS (-1.71; P = 0.003), and IWQOL-Lite (-3.72; P = 0.002), but not MCS (P = 0.69). The strongest predictors (all P < 0.005) for impairment in each instrument were: fibromyalgia for PCS (-5.84 points), depression for MCS (-7.49 points), stroke for EQ-index (-0.17 points), less than full-time employment for EQ-VAS (-7.06 points), and coronary disease for IWQOL-Lite (-10.86 points). Chronic pain, depression, and sleep apnea were associated with reduced HRQL using all instruments., Conclusion: The clinical impact of BMI on physical and general HRQL was small, and mental health scores were not associated with BMI. Chronic pain, depression, and sleep apnea were consistently associated with lower HRQL., (Copyright © 2014 The Obesity Society.)

Background: Paint laden with polychlorinated biphenyls (PCBs) often acts as a point source for environmental contamination. It is advantageous to address contaminated paint before the PCBs transport to surrounding media; however, current disposal methods of painted material introduce a variety of complications. Previous work demonstrates that PCBs can be broken down at ambient temperatures and pressures through a degradation process involving magnesium metal and acidified ethanol. This report is an extension of that work by describing the development of a delivery system for said reaction in preparation for a field test. Two treatment options including the Activated Metal Treatment System (AMTS) and the Non-Metal Treatment System (NMTS) remove and degrade PCBs from painted surfaces., Findings: AMTS decreased the Aroclor® concentration of a solution by more than 97% within 120 minutes and the Aroclor® concentration of industrial paint chips by up to 98% over three weeks. After removing up to 76% of PCBs on a painted surface after seven days, NMTS also removed trace amounts of PCBs in the paint's concrete substrate. The evaporation rate of the solvent (ethanol) from the treatment system was reduced when the application area was increased. The solvent system's ability to remove more than 90% of PCBs was maintained after losing 36% of its mass to solvent evaporation., Conclusions: The delivery systems, AMTS and NMTS, are able to support the hydrodechlorination reaction necessary for PCB degradation and are therefore attractive options for further studies regarding the remediation of contaminated painted surfaces.

Background: Multidisciplinary bariatric care is increasingly being delivered in Canada within publicly funded regional programs. Demand is high, wait lists are long, and clinical effectiveness is unknown., Objective: To examine the "real-world" outcomes associated with a publicly funded, population-based regional bariatric (medical and surgical) program., Research Design: Prospective observational cohort., Subjects: Five hundred consecutive patients (150 wait-listed, 200 medically treated, 150 surgically treated) from the Edmonton Weight Wise program were enrolled., Measures: The primary outcome was weight change (kg). Between-group changes were analyzed using multivariable regression adjusted for age, sex, and baseline weight and "last-observation-carried-forward" was used for missing data. Subjects transitioning between groups (wait-list to medical or medical to surgery) were censored when crossing over., Results: At baseline, mean age was 43.7 ± 9.6 years, mean body mass index was 47.9 ± 8.1 kg/m, and 88% were female. A total of 412 subjects (82%) completed 2-year follow-up and 143 (29%) subjects crossed over to the next treatment phase. Absolute and relative (% of baseline) mean weight reductions were 1.5 ± 8.5 kg (0.9 ± 6.1%) for wait-listed, 4.1 ± 11.6 kg (2.8 ± 8.1%) for medically treated, and 22.0 ± 19.7 kg (16.3 ± 13.5%) for surgically treated (P<0.001) subjects. For surgery, weight reductions were 7.0 ± 9.7 kg (5.8 ± 7.9%) with banding, 21.4 ± 16.0 kg (16.4 ± 11.6%) with sleeve gastrectomy, and 36.6 ± 19.5 kg (26.1 ± 12.2%) with gastric bypass (P<0.001). Rates of hypertension, diabetes, and dyslipidemia decreased to a significantly greater degree with surgery than medical management (P<0.001) and stayed the same or increased in wait-listed subjects., Conclusions: Population-based bariatric care, particularly bariatric surgery, was clinically effective. Weight and cardiometabolic risk was relatively stable wait-listed patients receiving "usual care."