Amnesia Interrupted: Re-Membering the Living Past in Feminist Theory and Suzanne Lacy's Crystal Quilt

Amnesia Interrupted: Re-Membering the Living Past in Feminist Theory and Suzanne Lacy's Crystal Quil

TimeSlips: Creativity for People with Dementia

Educational Objectives 1. Recognize the value of creative storytelling for people with dementia, with its shift in emphasis from memory to imagination. 2. Understand the impact of creative storytelling upon facilitators, storytellers, audiences, and readers. 3. Explore the potential mechanisms at work in creative storytelling

The arts as a medium for care and self-care in dementia: arguments and evidence

The growing prevalence of dementia, combined with an absence of effective pharmacological treatments, highlights the potential of psychosocial interventions to alleviate the effects of dementia and enhance quality of life. With reference to a manifesto from the researcher network Interdem, this paper shows how arts activities correspond to its definition of psycho-social care. It presents key dimensions that help to define different arts activities in this context, and illustrates the arts with reference to three major approaches that can be viewed online; visual art, music and dance. It goes on to discuss the features of each of these arts activities, and to present relevant evidence from systematic reviews on the arts in dementia in general. Developing the analysis into a template for differentiating arts interventions in dementia, the paper goes on to discuss implications for future research and for the uptake of the arts by people with dementia as a means to self-care

The field of disease management at the crossroads: An interview with David B. Nash, MD, MBA

As David B. Nash, MD, MBA, takes the helm of Disease Management as Editor-in-Chief, the practice of disease management—now a decade old—depends on its practitioners to continue to provide economic proof of concept. This effort to accrue the credibility needed to design and fund programs will provide further evidence that new technologies can be integrated into care programs across large populations to reduce costs while improving healthcare and access to it

Praxis: An Editorial Statement

Praxis: An Editorial Statemen

'Singing for the Brain': a qualitative study exploring the health and well-being benefits of singing for people with dementia and their carers

Dementia has detrimental effects on cognitive, psychological and behavioural functioning, as well as significant impact on those who provide care. There is a need to find suitable psychosocial interventions to help manage the condition, enhance well-being, and to provide support for caregivers. This study explored the impact of Singing for the Brain™, an intervention based on group singing activities developed by The Alzheimer’s Society for people with dementia and their carers. This qualitative study used semi-structured interviews with people with dementia and their carers. Ten interviews involving 20 participants were analysed thematically. Social inclusiveness and improvements in relationships, memory and mood were found to be especially important to participants. As well as enjoying the sessions, participants found that attending Singing for the Brain™ helped in accepting and coping with dementia

NMR, EM and functional studies on TBsmr, a small multidrug transporter from M. tuberculosis

Antibiotic resistance of pathogenic bacteria is a major worldwide problem. Bacteria can resist antibiotics by active efflux due to multidrug efflux pumps. The focus of this study has been the mycobacterial multidrug transporter TBsmr because it belongs to the small multidrug resistance (SMR) family whose members are a paradigm to study multidrug efflux due to their small size. SMR proteins are typically 11-12 kDa in size and have a four-transmembrane helix topology. They bind cationic, lipophilic antibiotics such as ethidium bromide (EtBr) and TPP+, and transport them across the membrane in exchange for protons. To understand the molecular mechanism of multidrug resistance, we have to gain information about the structure and function of these proteins. The research described in this thesis aimed to deduce details about the topology, transport cycle and key residues of TBsmr using biophysical techniques. Solid-state NMR (ssNMR) can provide detailed insight into structural organization and dynamical properties of these systems. However, a major bottleneck is the preparation of mg amounts of isotope labeled protein. In case of proteoliposomes, the problem is compounded by the presence of lipids which have to fit into the small active volume of the ssNMR rotor. In Chapter 3, an enhanced protein preparation is described which yields large amounts of TBsmr reconstituted in a native lipid environment suitable for further functional and structual studies. The achieved high protein-to-lipid ratios made a further characterization by ssNMR feasible. The transport activity and oligomeric state of the reconstituted protein in different types of lipid was studied as shown in Chapter 4. The exact oligomeric state of native SMR proteins is still uncertain but a number of biochemical and biophysical studies in detergent suggest that the minimal functional unit capable of binding substrate is a dimer. However, binding assays are not ideal since a protein may bind substrate without completing the transport cycle which can only be shown for reconstituted protein in transport assays.By combining functional data of a TPP+ transport assay with information about theoligomeric state of reconstituted TBsmr obtained by freeze-fracture electron microscopy, it could be shown that lipids affect the function and the oligomeric state of the protein, and that the TBsmr dimer is the minimal functional unit necessary for transport. The transport cycle must involve various conformational states of the protein needed for substrate binding, translocation and release. A fluorescent substrate will therefore experience a significant change of environment while being transported, which influences its fluorescence properties. Thus the substrate itself can report intermediate states that form during the transport cycle. In Chapter 5, the existence of such a substrate-transporter complex for the TBsmr and its substrate EtBr could be shown. The pH gradient needed for antiport has been generated by co-reconstituting TBsmr with bacteriorhodopsin. The measurements have shown the formation of a pH-dependant, transient substrate-protein complex between binding and release of EtBr. This state was further characterized by determining the Kd, by inhibiting EtBr transport through titration with non-fluorescent substrate and by fluorescence anisotropy measurements. The findings support a model with a single occluded intermediate state in which the substrate is highly immobile. Liquid-state NMR is a useful tool to monitor protein-ligand interactions by chemical shift mapping and thus identify and characterize important residues in the protein which are involved in substrate binding. In agreement with previous studies (Krueger-Koplin et al., 2004), the detergent LPPG was found to be highly suitable for liquid-state NMR studies of the membrane protein TBsmr and 42% of the residues could be assigned, as reported in Chapter 6. However, no specific interactions with EtBr were found. This observation was confirmed by LILBID mass spectrometry which showed that TBsmr was predominantly in the non-functional monomeric state. Functional protein was prepared in proteoliposomes which can be investigated by solidstate NMR (Chapter 7). Besides the essential E13, the aromatic residues W63, Y40, and Y60 have been shown to be directly involved in drug binding and transport. Different isotope labeling strategies were evaluated to improve the quality of the NMR spectra to identify and characterize these key residues. In a single tryptophan mutant of reconstituted TBsmr W30A, the binding of ethidium bromide could be detected by 13C solid-state NMR. The measurements have revealed two populations of the conserved W63 residue with distinct backbone structures in the presence of substrate. There is a controversy about the parallel or anti-parallel arrangement of the protomers in the EmrE dimer (Schuldiner, 2007) but this structural asymmetry is consistent with both a parallel and anti-parallel topology.Die Antibiotikaresistenz pathogener Bakterien ist ein Problem für die Gesundheit von Menschen weltweit und damit ein wichtiges Forschungsziel. Ein Mechanismus zur Resistenz gegen Antibiotika ist der aktive Transport von Antibiotika aus der Zelle heraus durch so genannte Multidrug-Transportproteine. Zusätzlich sind diese Transporter als Modellsysteme auch von großem generellem Interesse, denn ihre erstaunliche Fähigkeit, eine Vielzahl sehr diverser Wirkstoffe spezifisch zu binden, scheint den verbreiteten Ansichten über Substrat-Protein-Wechselwirkung zu widersprechen. Zur Untersuchung des Multidrug-Transports befasst sich die vorliegende Arbeit mit der SMR-Familie (small multidrug resistance), deren Mitglieder sich auf Grund ihrer kleinen Größe hervorragend als Modellsysteme eignen. Die SMR-Proteine sind typischerweise 11-12 kDa schwer und bestehen aus vier transmembranen ? - Helizes. Sie transportiere eine Reihe unterschiedlicher aromatischer und positiv geladener Substrate wie zum Beispiel Ethidium Bromid im Austausch gegen Protonen durch die Membran. Um offene strukturelle und mechanistische Fragen zu beantworten, wurde TBsmr von M. tuberculosis, als ein typisches SMR Protein, ausgewählt. Ziel dieser Arbeit war es, ein besseres Verständnis von der Oligomerisierung, dem Transportzyklus und wichtigen, konservierten Aminosäuren der SMR-Familie durch Untersuchungen mit biophysikalischen Methoden zu bekommen. Die Festkörper-NMR-Spektroskopie eignet sich, um Informationen über die Struktur und Dynamik dieser Systeme zu erhalten. Vorteilhaft sind Messungen an Proteoliposomen, da sich das Protein dann in seiner nativen Membranumgebung befindet. Die Notwendigkeit von mg-Mengen isotopenmarkierter Proteine ist aber ein großer Engpass bei der Umsetzung. Der Nachteil dieser Proben ist darüber hinaus das zusätzliche Volumen durch Lipide, da die Festkörper-NMR-Rotoren nur ein geringes Probenvolumen fassen. Durch eine verbesserte Probenpräparation ließen sich große Mengen isotopenmarkiertes TBsmr gewinnen und mit einem hohen Protein-zu-Lipid Verhältnis in Liposomen rekonstituieren. Diese Verbesserungen ermöglichten die nachfolgenden Messungen zur Charakterisierung von TBsmr. Der Oligomerisierungszustand der nativen SMR-Proteine ist noch nicht sicher bestimmt, aber die meisten biochemischen und biophysikalischen Untersuchungen in Detergenz deuten darauf hin, dass ein Dimer die minimale funktionelle Einheit ist, die Substrat binden kann. Ligand-Bindungs-Experimente haben aber den Nachteil, dass eventuell Substrat an das Protein bindet, es aber trotzdem nicht transportiert werden kann. Daher wurde der Transport des Substrats Tetraphenylphosphonium (TPP+) in verschiedenen Lipiden untersucht. Die Messungen erfolgten mit Hilfe von pH-Sprüngen und einer TPP+ -sensitiven Elektrode. Dabei wurde ein Einfluss der Lipidsorte auf die Aktivität und den Oligomerisierungszustand von TBsmr festgestellt. Durch Kombination mit Informationen über den Oligomerisierungsgrad des rekonstitutierten Proteins aus Gefrierbruch-Elektronenmikroskopie-Untersuchungen, konnte die Existenz von funktionalen Dimeren, die Substrat transportieren, in POPC nachgewiesen werden. In Übereinstimmung mit bisherigen Untersuchungen, die auf die Existenz höherer Oligomere hindeuten, wurden in E. coli Lipiden Tetramere gefunden. Der Transportzyklus muss eine Reihe von verschiedenen Konformationen für die Bindung, den Transport und die Freisetzung des Substrats enthalten. Eine fluoreszierende Substanz wird sich beim Transport durch die starken Änderungen der Umgebung in ihren Fluoreszenzeigenschaften verändern. Deshalb könnte das Substrat selbst als Reporter für Zwischenzustände im Transportzyklus benutzt werden. Es konnte die Existenz eines solchen Substrat-Transporter-Komplexes für TBsmr und das Substrat Ethidium Bromid mit einem neu entwickelten Assay nachgewiesen werden. Die Möglichkeit eines stabilen pH-Gradienten wurde durch die Korekonstitution von TBsmr mit Bakteriorhodopsin geschaffen. Die beobachtete Fluoreszenzänderung wurde durch einen pH-abhängigen, transienten Substrat-Protein-Komplex zwischen der Bindung und der Freisetzung von Ethidium verursacht. Zusätzlich wurde dieser Zustand durch die Bestimmung eines Kds, der Hemmung des Ethidiumtransports durch die Titration mit einem nicht fluoreszierenden Substrat und durch Fluoreszenzanisotropie-Messungen genauer charakterisiert. Die Ergebnisse deuten auf einen einzelnen verdeckten Übergangszustand hin, in dem das Substrat unbeweglich ist. Lösungs-NMR-Experimente wurden durchgeführt, um zu evaluieren, ob Substrat-Protein-Interaktionen gemessen werden können. Dabei eignete sich besonders das Detergenz LPPG und es war möglich, 42 Prozent aller Resonanzen des Protein-Rückgrates vorläufig zuzuordnen. Es konnten aber keine spezifische Interaktion von TBsmr mit Ethidium Bromid nachgewiesen werden. Die Beobachtungen wurden durch LILBID-Massenspektrometrie-Messungen (Laser Induced Liquid Beam Ionization/Desorption) unterstützt, welche nicht-funktionale TBsmr Monomere in LPPG nachwiesen. Das Problem einer funktionalen Präparation ließ sich durch Aktivität in Lipidmembranen lösen, wo Membranproteine sehr gut mittels Festkörper-NMR untersucht werden können. Neben dem essentiellen Glutamat 13 sind einige weitere, aromatische Aminosäuren (Y40, Y60, W63) für den Transportzyklus wichtig. Es wurden Festkörper-NMR-Messungen an vollständig und selektiv markierten Proben durchgeführt, um durch verschiedene Isotopenmarkierungs-Schemata die Qualität der NMR-Spektren soweit zu verbessern, dass einzelne Aminosäuren identifiziert und charakterisiert werden können. Mit der Mutante TBsmr W30A, in der ein einzelnes Tryptophan vollständig mit 13C Isotopen markiert war, konnte die Bindung von Ethidium Bromid detektiert werden. Die Messungen offenbarten zwei Populationen der konservierten Aminosäure W63 mit verschiedenen Konformationen des Peptidrückgrats in Gegenwart von Substrat. Die beobachtete strukturelle Asymmetrie von W63 ist sowohl in einer parallelen, wie auch anti-parallelen Topologie der Dimere möglich

Estimating The Burden Of Covid-19 Associated Hospitalizations In Connecticut

The number of COVID-19 related hospitalizations that occur in a particular area is dependent on a variety of sociodemographic and clinical factors, but the percentage of hospitalizations that are identified in that region varies based on the type and quality of surveillance system that is utilized. In Connecticut, an active surveillance system called the COVID-19–Associated Hospitalization Surveillance Network (COVID-NET) conducts COVID-19 associated hospitalization surveillance in two of Connecticut’s eight counties. The other counties in Connecticut rely on a passive surveillance system which could be subject to underreporting. To evaluate possible underreporting, positive SARS-CoV-2 test rates obtained from the Connecticut Department of Public Health (CT DPH) and variables from the CDC’s Social Vulnerability Index (SVI) were used as covariates in a negative binomial regression model. The model was fit to random samples of COVID-NET hospitalization data through an iterative process and ten optimal models were selected using stepwise Akaike’s Information Criterion (AIC). The average of the regression coefficients for each covariate included in the ten optimal models was calculated and multiplied by a model matrix containing the original SVI and SARS-CoV-2 testing covariates for each census tract in Connecticut to produce census tract-level estimates of COVID-19 related hospitalizations in Connecticut. Based on the model estimates, 5,600 excess hospitalizations occurred throughout 2020 compared to the number passively reported to CT DPH. Of note, New London County had the largest discrepancy between observed and estimated hospitalization rates (255 hospitalizations per 100,000), and New Haven and Middlesex counties (the counties which comprise the COVID-NET catchment area) had the lowest discrepancy (45 hospitalizations per 100,000 and 56 hospitalizations per 100,000, respectively). Widespread underreporting of COVID-19 related hospitalizations in Connecticut has broad implications. These surveillance gaps must be addressed to achieve more equitable pandemic planning and response

P1: Can\u27t Shake the Blues: Do Worry and Attention Flexibility Enervate Cognitive Emotion Regulation Outcomes

Depression is a mood disorder that is characterized by enduring feelings of sadness that are often accompanied by psychovegetative symptoms and attentional deficits that result in functional impairment. Depression is often hallmarked by biased attention towards negative information that once activated, remains in depressed persons conscious awareness. Generalized anxiety disorder (GAD) often co-occurs with depression, and is also characterized by enduring negative information processing in the form of worry that consumes a significant amount of an individual\u27s thought processes. Both disorders are marked by emotion regulation deficits in the form of responses that usually reduce distress, but that fail to work for those with either disorder. Despite the high rates of co-occurrence, relatively little is known about the effect that GAD has on the relationship between depression and emotion regulation outcomes. Given that worry is a cognitive process that evokes and maintains negative information in conscious awareness, it is feasible that GAD may interfere with the effects of emotion regulation responses that leverage cognitive resources to bring forth and maintain positive emotions, such as by recalling pleasant memories (positive autobiographical memory, PAM). Deficits in attentional processes may further reduce PAM\u27s effectiveness. This study examined these possibilities among community dwelling adults.https://engagedscholarship.csuohio.edu/u_poster_2017/1039/thumbnail.jp

Carers’ responses to shifting identity in dementia in Iris and Away From Her: cultivating stability or embracing change?

An emphasis on supporting and maintaining self-identity in people who have dementia for as long as possible has gone hand in hand with the revitalisation of dementia interventions, services and empowerment. However, recognition of the need for change, adaptation and personal growth is as necessary when living with dementia as at any other time in people's lives. Those who care for people with dementia must constantly navigate this tension between continuity and change within the context of memory loss, knowing when to respond by reinforcing the ‘self’ they have known over time, and when it may be better to respond by acknowledging the changes that have taken place in that ‘self’. The creative arts are avenues for the exploration of the caring relationship under these conditions, conveying the challenges and stimulating audiences to ask how they themselves might choose to respond in a similar situation. This article considers how the scenarios of two noted films, Iris (dir. Richard Eyre, 2001 UK)) and Away From Her (dir. Sarah Polley, 2006 Can), present the dilemmas of identity and caring. In both, a husband cares for a wife experiencing cognitive decline, but responds differently in each to her shifting needs and experience of identity. We argue that the two films reveal complementary and provocative perspectives on this situation. They offer no easy answers, but provide insights into the everyday decisions characteristic of caring for someone who has dementia