Dental coping strategies and dental anxiety: Adaptive and maladaptive strategies among adult patients with regular or irregular dental care

Abstract The overall aim of this thesis was to explore the reported use of coping strategies in connection with dental treatment among adult patients with dental anxiety and regular or irregular dental care. The specific aims of the four papers were (I) to develop a questionnaire for assessing coping strategies in the dental treatment situation and to evaluate its psychometric properties; (II) to further investigate and evaluate the newly constructed Dental Coping Strategy Questionnaire (DCSQ-15); (III) to investigate the relationship between the use of dental coping strategies in DCSQ-15, emotional distress and sociodemographic factors; (IV) to generate a conceptual framework explaining the main concerns of patients with dental anxiety who, despite their fear, participate in regular dental treatment, in order to acquire a deeper understanding of what they do to manage the dental-treatment situation. This thesis has a mixed-method design containing both quantitative and qualitative research components, i.e. both cross-sectional questionnaire surveys and qualitative in-depth interviews. The overall findings showed that adult patients with dental anxiety and regular dental attendance use more adaptive coping strategies. In Paper I, the Dental Coping Strategy Questionnaire (DCSQ-20) instrument showed sound psychometric properties and good reliability with four factors of coping strategies labeled Self-efficacy statements, Distraction and distancing, Catastrophizing and Praying and despair. Catastrophizing and Praying and despair were significantly higher correlated with dental anxiety and were rated significantly higher among irregular attendees. Gender (male) and having high levels of dental anxiety, Catastrophizing and Praying and despair were predictive of irregular dental care. Paper II focused on adaptive coping and a new instrument, the DCSQ-15, was constructed from the DCSQ-20, displaying five factors of coping strategies labeled Self-efficacy, Self-distraction, Distancing, Praying and Optimism. The factors of Praying and Optimism were significantly higher correlated with dental anxiety and were assessed significantly higher and lower, respectively by patients with irregular dental care. Gender (male), having a high level of dental anxiety and using little Optimism were predictive of irregular dental care. In Paper III, the results showed that the level of general anxiety and depression was significantly higher among irregular attendees, who also showed lower levels of adaptive coping strategies. Gender (male), high levels of dental anxiety and general anxiety and the non-use of the coping strategy of Optimism were predictive of irregular dental care. In Paper IV, a grounded theory study, the main concern of the fearful patients who participated in dental care was identified as “making dental care possible – a mutual affair”, comprising the close and trust-filled interplay between the patient and the dental staff that makes dental care possible, and four additional categories with coping strategies were identified. The conclusions were that regular attendees reported greater use of adaptive coping strategies and that the use of optimistic thinking was predictive of regular dental care. Risk factors for irregular dental care were being of male gender, having high levels of dental or general anxiety and relying on the maladaptive coping strategy of Praying, as well as catastrophic thinking. It is suggested in Paper IV, that the patients logical argumentation with themselves, social support, feelings of control during treatment and trust-filled interplay between the patient and the dental staff are of great importance in making dental care possible and maintaining regular dental care among patients with dental anxiety

Impact of killer-immunoglobulin-like receptor and human leukocyte antigen genotypes on the efficacy of immunotherapy in acute myeloid leukemia

Interactions between killer-immunoglobulin-like receptors (KIRs) and their HLA class I ligands are instrumental in natural killer (NK) cell regulation and protect normal tissue from NK cell attack. Human KIR haplotypes comprise genes encoding mainly inhibitory receptors (KIR A) or activating and inhibitory receptors (KIR B). A substantial fraction of humans lack ligands for inhibitory KIRs (iKIRs), that is, a 'missing ligand' genotype. KIR B/x and missing ligand genotypes may thus give rise to potentially autoreactive, unlicensed NK cells. Little is known regarding the impact of such genotypes in untransplanted acute myeloid leukemia (AML). For this study, NK cell phenotypes and KIR/HLA genotypes were determined in 81 AML patients who received immunotherapy with histamine dihydrochloride and low-dose IL-2 for relapse prevention (NCT01347996). We observed that presence of unlicensed NK cells impacted favorably on clinical outcome, in particular among patients harboring functional NK cells reflected by high expression of the natural cytotoxicity receptor (NCR) NKp46. Genotype analyses suggested that the clinical benefit of high NCR expression was restricted to patients with a missing ligand genotype and/or a KIR B/x genotype. These data imply that functional NK cells are significant anti-leukemic effector cells in patients with KIR/HLA genotypes that favor NK cell autoreactivity

Strategiskt beslutsfattande vid påtvingade förändringar - en fallstudie av studentnationerna i Lund

En kvalitativ fallstudie där syftet har varit att undersöka hur tjänsteorganisationer i stabila miljöer strategiskt hanterar en omvälvande extern förändring och vilka problem de ställs inför i samband med detta

The value of a common approach to lean

Thesis (S.M.)--Massachusetts Institute of Technology, Sloan School of Management; and, (S.M.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering; in conjunction with the Leaders for Manufacturing Program at MIT, 2004.Includes bibliographical references (p. 83-84).ABB is a world leader in power and automation technologies working to enable utility and industry customers to improve operations. Competition in these markets is increasing and in order to retain their competitive position, ABB must strive to improve their operations by reducing costs and delivery times. Most ABB factories still operate on push principles with long throughput time, high inventories, and high overhead In order to remain competitive these factories have decided to transform their businesses reduce costs and increase speed. The strategy to achieve this in the power technologies distribution transformer (PTDT) factories is to develop a standard approach to lean manufacturing for implementation in factories around the world. The thesis will describe standard approaches to lean proposed by academics and used by other leading companies; analyzing at the frameworks used including implementation practices, tools, and results. With an understanding of how other companies implement lean manufacturing techniques, this thesis will then describe the creation of a standard approach to lean for ABB PTDT factories, examining the methodology of the approach including the implementation process, common production practices, tools used, and evaluation techniques. Two case studies will be used to describe the implementation of these lean manufacturing techniques at the Monselice, Italy and Zaragoza, Spain factories. Using the Monselice and Zaragoza case studies, along with results seen by other companies, this thesis will analyze the benefits of a standard approach to lean as it relates to the creation of a corporate culture; improvements in implementation results, and increasing ease of implementation.by Michelle Elisabeth Bernson.S.M

Amyloid formation of fish β-parvalbumin involves primary nucleation triggered by disulfide-bridged protein dimers

Amyloid formation involves the conversion of soluble protein species to an aggregated state. Amyloid fibrils of β-parvalbumin, a protein abundant in fish, act as an allergen but also inhibit the in vitro assembly of the Parkinson protein α-synuclein. However, the intrinsic aggregation mechanism of β-parvalbumin has not yet been elucidated. We performed biophysical experiments in combination with mathematical modeling of aggregation kinetics and discovered that the aggregation of β-parvalbumin is initiated by the formation of dimers stabilized by disulfide bonds and then proceeds via primary nucleation and fibril elongation processes. Dimer formation is accelerated by H2O2 and hindered by reducing agents, resulting in faster and slower aggregation rates, respectively. Purified β-parvalbumin dimers readily assemble into amyloid fibrils with similar morphology as those formed when starting from monomer solutions. Furthermore, addition of preformed dimers accelerates the aggregation reaction of monomers. Aggregation of purified β-parvalbumin dimers follows the same kinetic mechanism as that of monomers, implying that the rate-limiting primary nucleus is larger than a dimer and/or involves structural conversion. Our findings demonstrate a folded protein system in which spontaneously formed intermolecular disulfide bonds initiate amyloid fibril formation by recruitment of monomers. This dimer-induced aggregation mechanism may be of relevance for human amyloid diseases in which oxidative stress is often an associated hallmark

Graphene oxide sheets and quantum dots inhibit alpha-synuclein amyloid formation by different mechanisms

Aggregation and amyloid formation of the 140-residue presynaptic and intrinsically disordered protein alpha-synuclein (alpha-syn) is a pathological hallmark of Parkinson\u27s disease (PD). Understanding how alpha-syn forms amyloid fibrils, and investigations of agents that can prevent their formation is therefore important. We demonstrate herein that two types of graphene oxide nanoparticles (sheets and quantum dots) inhibit alpha-syn amyloid formation by different mechanisms mediatedviadifferential interactions with both monomers and fibrils. We have used thioflavin-T fluorescence assays and kinetic analysis, circular dichroism, dynamic light scattering, fluorescence spectroscopy and atomic force microscopy to asses the kinetic nature and efficiency of this inhibitory effect. We show that the two types of graphene oxide nanoparticles alter the morphology of alpha-syn fibrils, disrupting their interfilament assembly and the resulting aggregates therefore consist of single protofilaments. Our results further show that graphene oxide sheets reduce the aggregation rate of alpha-syn primarily by sequestering of monomers, thereby preventing primary nucleation and elongation. Graphene quantum dots, on the other hand, interact less avidly with both monomers and fibrils. Their aggregation inhibitory effect is primarily related to adsorption of aggregated species and reduction of secondary processes, and they can thus not fully prevent aggregation. This fine-tuned and differential effect of graphene nanoparticles on amyloid formation shows that rational design of these nanomaterials has great potential in engineering materials that interact with specific molecular events in the amyloid fibril formation process. The findings also provide new insight into the molecular interplay between amyloidogenic proteins and graphene-based nanomaterials in general, and opens up their potential use as agents to manipulate fibril formation

Redox-Dependent Copper Ion Modulation of Amyloid-β (1-42) Aggregation In Vitro

Plaque deposits composed of amyloid-β (Aβ) fibrils are pathological hallmarks of Alzheimer’s disease (AD). Although copper ion dyshomeostasis is apparent in AD brains and copper ions are found co-deposited with Aβ peptides in patients’ plaques, the molecular effects of copper ion interactions and redox-state dependence on Aβ aggregation remain elusive. By combining biophysical and theoretical approaches, we here show that Cu2+\ua0(oxidized) and Cu+\ua0(reduced) ions have opposite effects on the assembly kinetics of recombinant Aβ(1-42) into amyloid fibrils in vitro. Cu2+\ua0inhibits both the unseeded and seeded aggregation of Aβ(1-42) at pH 8.0. Using mathematical models to fit the kinetic data, we find that Cu2+\ua0prevents fibril elongation. The Cu2+-mediated inhibition of Aβ aggregation shows the largest effect around pH 6.0 but is lost at pH 5.0, which corresponds to the pH in lysosomes. In contrast to Cu2+, Cu+\ua0ion binding mildly catalyzes the Aβ(1-42) aggregation via a mechanism that accelerates primary nucleation, possibly via the formation of Cu+-bridged Aβ(1-42) dimers. Taken together, our study emphasizes redox-dependent copper ion effects on Aβ(1-42) aggregation and thereby provides further knowledge of putative copper-dependent mechanisms resulting in AD

Downregulation of HLA Class I Renders Inflammatory Neutrophils More Susceptible to NK Cell-Induced Apoptosis

Neutrophils are potent effector cells and contain a battery of harmful substances and degrading enzymes. A silent neutrophil death, i.e., apoptosis, is therefore of importance to avoid damage to the surrounding tissue and to enable termination of the acute inflammatory process. There is a pile of evidence supporting the role for pro-inflammatory cytokines in extending the life-span of neutrophils, but relatively few studies have been devoted to mechanisms actively driving apoptosis induction in neutrophils. We have previously demonstrated that natural killer (NK) cells can promote apoptosis in healthy neutrophils. In this study, we set out to investigate how neutrophil sensitivity to NK cell-mediated cytotoxicity is regulated under inflammatory conditions. Using in vitro-activated neutrophils and a human skin chamber model that allowed collection of in vivo-transmigrated neutrophils, we performed a comprehensive characterization of neutrophil expression of ligands to NK cell receptors. These studies revealed a dramatic downregulation of HLA class I molecules in inflammatory neutrophils, which was associated with an enhanced susceptibility to NK cell cytotoxicity. Collectively, our data shed light on the complex regulation of interactions between NK cells and neutrophils during an inflammatory response and provide further support for a role of NK cells in the resolution phase of inflammation