External health locus of control and general self-efficacy: Moderators of emotional distress among university students

A belief that doctors or family control one's health outcomes (external health locus of control), and a belief in one's own ability to achieve desired outcomes (general self-efficacy), may influence distress experienced in relation to a physical illness. This study examined the interaction between illness severity, external health locus of control and general self-efficacy in relation to distress. Illness severity was defined as acute or chronic illness, with the latter expected to be more stressful. Participants described a serious illness they experienced, and completed self-report scales in relation to it. Results confirmed that chronic illnesses were associated with more distress than acute illnesses across the sample. Hierarchical multiple regression analyses supported the predicted effects on distress of a three-way interaction involving external health locus of control, general self-efficacy and illness severity (acute vs. chronic). Analysis of these results may assist in explaining inconsistencies in previous research, and offer a model for understanding the role of person variables in emotional distress.

Blockade of the C5a receptor fails to protect against experimental autoimmune encephalomyelitis in rats

Complement activation contributes to inflammation and tissue damage in human demyelinating diseases and in rodent models of demyelination. Inhibitors of complement activation ameliorate disease in the rat model antibody-dependent experimental autoimmune encephalomyelitis and rats unable to generate the membrane attack complex of complement develop inflammation without demyelination. The role of the highly active chemotactic and anaphylactic complement-derived peptide C5a in driving inflammation and pathology in rodent models of demyelination has been little explored. Here we have used a small molecule C5a receptor antagonist, AcF-[OPdChaWR], to examine the effects of C5a receptor blockade in rat models of brain inflammation and demyelination. C5a receptor antagonist therapy completely blocked neutrophil response to C5a in vivo but had no effect on clinical disease or resultant pathology in either inflammatory or demyelinating rat models. We conclude that C5a is not required for disease induction or perpetuation in these strongly complement-dependent disease models.

Tumour necrosis factor inhibitors

The cytokine, tumour necrosis factor-alpha (TNF-alpha) plays a key role in the pathogenesis of many chronic inflammatory and rheumatic diseases, in particular, Crohn's disease, rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. Controlled trials have shown that the TNF inhibitors (etanercept, infliximab and adalimumab) significantly reduce symptoms and signs, improve function and quality of life, and reduce radiologically evident damage in patients with rheumatoid diseases. For reasons that are not entirely clear, etanercept does not work in Crohn's disease. Injection site and intravenous reactions and increased risk of infection (in particular, reactivation of tuberculosis) are associated with the use of these agents. Increased risk of lymphoproliferative disease, the development of lupus-like syndromes and demyelination, including optic neuritis and reactivation of multiple sclerosis, are under evaluation in long-term follow-up studies. The TNF inhibitors are expensive (about $18000 per year), and in some patients need to be given continuously to maintain benefit, even in the presence of other immunosuppressive therapy.

IL10 and IL12B polymorphisms each influence IL-12p70 secretion by dendritic cells in response to LPS

Dendritic cells (DC) are the main producers of the cytokine IL-12p70, through which they play a direct role in the development of IFN-gamma-secreting Th1 cells, costimulation of CTL differentiation and NK-cell activation. In contrast, IL-10, which is also produced by DC, negatively regulates IL-12 production. IL-12p70 production varies widely between individuals, and several polymorphisms in the gene encoding IL-12p40 (IL12B) have been identified that influence susceptibility and severity of infectious, autoimmune and neoplastic disease. Here we show that polymorphisms not only of IL12B, but also in the IL10 promoter, influence IL-12p70 secretion by monocyte-derived DC in response to LPS. Although IL12B promoter homozygotes were prone to making more IL-12p70, presence of the IL10 high genotype restricted IL-12p70 production in these individuals. These observations provide a further genetic control of IL-12p70 regulation and emphasize the complexity of production of this cytokine. They also suggest genotypes that might influence the outcome of DC immunotherapy.

The psychosocial impact of caregiving on young people who have a parent with an illness or disability: Comparisons between young caregivers and noncaregivers

Objective: To investigate the psychosocial impact of young caregiving by empirically validating prominent qualitative themes.. This was achieved through developing an inventory called the Young Caregiver of Parents Inventory (YCOPI) designed to assess these themes and by comparing young caregivers and noncaregivers. Method: Two hundred forty-five participants between 10 and 25 years completed questionnaires: 100 young caregivers and 145 noncaregivers. In addition to the YCOPI, the following variables were measured: demographics, caregiving context, social support, appraisal, coping strategies, and adjustment (health, life satisfaction, distress, positive affect). Results: Eight reliable factors emerged from the YCOPI that described the diverse impacts of caregiving and reflected the key themes reported in prior research. The factors were related to most caregiving context variables and theoretically relevant stress and coping variables. Compared with noncaregivers, young caregivers reported higher levels of young caregiving impact, less reliance on problem-solving coping, and higher somatization and lower life satisfaction. Conclusions: Findings delineate key impacts of young caregiving and highlight the importance of ensuring that measures used in research on young caregivers are sensitive to issues pertinent to this population.

Recent advances in the development of tissue transglutaminase (TG2) inhibitors

Tissue transglutaminase (TG2) is a Ca2+-dependent enzyme and probably the most ubiquitously expressed member of the mammalian transglutaminase family. TG2 plays a number of important roles in a variety of biological processes. Via its transamidating function, it is responsible for the cross-linking of proteins by forming isopeptide bonds between glutamine and lysine residues. Intracellularly, Ca2+ activation of the enzyme is normally tightly regulated by the binding of GTP. However, upregulated levels of TG2 are associated with many disease states like celiac sprue, certain types of cancer, fibrosis, cystic fibrosis, multiple sclerosis, Alzheimer's, Huntington's and Parkinson's disease. Selective inhibitors for TG2 both cell penetrating and non-cell penetrating would therefore serve as novel therapeutic tools for the treatment of these disease states. Moreover, they would provide useful tools to fully elucidate the cellular mechanisms TG2 is involved in and help comprehend how the enzyme is regulated at the cellular level. The current paper is intended to give an update on the recently discovered classes of TG2 inhibitors along with their structure-activity relationships. The biological properties of these derivatives, in terms of both activity and selectivity, will also be reported in order to translate their potential for future therapeutic developments. © 2011 Springer-Verlag.

Dipeptidyl peptidase IV (DPP IV) and related molecules in type 2 diabetes

Dipeptidyl peptidase IV (DPP IV) is a widely distributed physiological enzyme that can be found solubilized in blood, or membrane-anchored in tissues. DPP IV and related dipeptidase enzymes cleave a wide range of physiological peptides and have been associated with several disease processes including Crohn's disease, chronic liver disease, osteoporosis, multiple sclerosis, eating disorders, rheumatoid arthritis, cancer, and of direct relevance to this review, type 2 diabetes. Here, we place particular emphasis on two peptide substrates of DPP IV with insulin-releasing and antidiabetic actions namely, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). The rationale for inhibiting DPP IV activity in type 2 diabetes is that it decreases peptide cleavage and thereby enhances endogenous incretin hormone activity. A multitude of novel DPP IV inhibitor compounds have now been developed and tested. Here we examine the information available on DPP IV and related enzymes, review recent preclinical and clinical data for DPP IV inhibitors, and assess their clinical significance.

Reducing suffering in experimental autoimmune encephalomyelitis (EAE)

This report is based on discussions and submissions from an expert working group consisting of veterinarians, animal care staff and scientists with expert knowledge relevant to the field. It aims to facilitate the implementation of the Three Rs (replacement, reduction and refinement) in the use of animal models or procedures involving experimental autoimmune encephalomyelitis (EAE), an experimental model used in multiple sclerosis research. The emphasis is on refinement since this has the greatest potential for immediate implementation. Specific welfare issues are identified and discussed, and practical measures are proposed to reduce animal use and suffering. Some general issues for refinement are summarised to help achieve this, with more detail provided on a range of specific measures to reduce suffering. © 2013 Elsevier Inc.

Need To Be Adored

Faced with a diagnosis of multiple sclerosis, I began with the objective of discovering methods for creating art that were still accessible to me. Along the way, I encountered others who had travelled this road before me. Their experiences led me to examine, not only my art, but also my political orientations, my love obligations and my transitioning self. In my varied art pieces, I conjure something from diverse sources and different worldviews, including contemporary feminist performance art and disability cultural theory. My thesis is a project. I make things: puppets, videos and performances, which included the exhibition, Need to be Adored (2014), staged in the digital media lab of the Isabel Bader Centre for the Performing Arts in Kingston, Ontario, Canada. The exhibition introduced thirteen of my puppets and a thirty-two-minute looped video. Following the exhibition, I put the puppets away and spent two years reading. Finally, taking my inspiration from Carolyn Ellis’s The Autoethnographic I (Ellis 2004), I turned my processes into words. I wrote out my experiences. I created an alternative text of my identity from an able-bodied cis-identified woman into a disabled trans-feminist artist academic. The writing required an uncomfortably intimate examination of my life. Nothing less than complete honesty would allow me to understand my new location. The resulting text is a lyrical and sometimes whimsical flow of consciousness that invites the reader to imagine what it might be like to engage in such a candid review of everything one holds close to one’s heart. Contained within are all my identities. In this text I let some out. This is a story of unsettling. I am working on my art practices, creating a cast of characters from cloth. Puppets. El becomes the exulted main character of a fictional accounting. She uncovers her queer roots and begins to see that she is at the centre of a very strange geography. Her desire to make film is revealed as she re-remembers her childhood through a disability lens.

Rôle des cellules myéloïdes dans des modèles murins de la neuroinflammation

L’inflammation du système nerveux central (SNC), appelée neuroinflammation, est un aspect inséparable des maladies neurodégénératives chroniques comme la sclérose en plaques (SEP) et la maladie d’Alzheimer (MA). La caractérisation de la signature moléculaire spécifique à chaque population cellulaire dans des pathologies distinctes va aboutir à la compréhension et donc au contrôle de la neuroinflammation. Le présent ouvrage a pour but de mieux comprendre les mécanismes d’action de deux types cellulaires myéloïdes, la microglie et les neutrophiles, au cours des affections neuroinflammatoires du SNC. Ainsi, le premier objectif a été de comprendre le rôle des cytokines IL-36 dans la neuroinflammation établie au cours de l’encéphalomyélite auto-immune expérimentale (EAE). Dans une seconde partie, l’objectif a été d’explorer l’action du GPR84, un récepteur couplé à la protéine G spécifique à la microglie dans le SNC, lors de l’altération des fonctions cérébrales dans un modèle de souris transgénique de la MA. Nos résultats démontrent que la voie de signalisation IL-36/IL36R est augmentée dans trois modèles différents de l’EAE, mais ne contribue pas au développement ni à la progression de la pathologie. En utilisant l’approche de cytométrie en flux nous identifions les neutrophiles comme la source majeure de l’IL-36γ. De plus, nous démontrons que la microglie exprime l’IL-36R et sa stimulation par l’IL-36γ conduit à la production de cytokines pro-inflammatoires. Dans un second temps, nous caractérisons l’augmentation de l’expression du GPR84 par la microglie dans le modèle murin de la MA APP/PS1. Ainsi, le croisement de ces souris avec des souris déficientes en GPR84 diminue l’activation et le recrutement de la microglie autour des plaques d’amyloïde-β et accélère le déclin cognitif. Nos études impliquent le GPR84 comme un acteur important dans le maintien de l’homéostasie neuronale puisque son absence favorise la dégénérescence des dendrites dans le cerveau. Les résultats obtenus dans cette thèse apportent de nouveaux éléments qui peuvent contribuer au développement des thérapies qui ciblent les cellules myéloïdes dans diverses pathologies du SNC. Ces données ouvrent de nouvelles pistes pour élucider le rôle de l’IL-36γ dans des maladies neurodégénératives. Enfin, pour une première fois, nous présentons un modèle murin permettant d’identifier le(s) ligand(s) endogène(s) du GPR84, une cible thérapeutique potentielle pour la prévention et/ou le traitement de la MA.

Copingstrategier i vardagen vid multipel skleros - En litteraturstudie

Multipel Skleros [MS] en är kronisk, neurologisk sjukdom som angriper det centrala nervsystemet genom nedbrytning av myelin, vilket försvårar nervsignalernas transport till målcellerna. Den som drabbats av MS kan uppleva symptom av fysisk och psykisk karaktär som pareser, spasticitet, koordinationsstörningar, fatigue, depression och ångest. För att hantera sjukdomen behöver personer med MS använda coping. Inom coping finns aktiva och passiva strategier. Till de aktiva copingstrategierna hör probleminriktad copingstrategi och emotionell copingstrategi och inom passiv hör undvikande copingstrategi. Syftet med studien var att beskriva användandet av copingstrategier hos personer diagnostiserade med MS utifrån en teoretisk referensram. Metoden som användes var litteraturstudie. Urvalet genomfördes utifrån Polit & Becks (2012) niostegsmodell. Sökningarna genomfördes i databaserna CINAHL, PsycInfo och PubMed. Efter urvalsprocessen kvarstod 14 artiklar som kom att ligga till grund för resultatet. Resultatet presenterades i tre kategorier, probleminriktad-, emotionell- och undvikande copingstrategi. De individuella förutsättningar som framkom vara centrala för användandet av copingstrategierna var resurser, acceptans, optimism, förnekelse och distansering. Information visade sig också genomsyra samtliga copingstrategier.  Slutsatsen var att en persons individuella förutsättningar var avgörande för hur coping användes. Sjuksköterskan har en viktig roll i att informera personer med MS om hur de kan använda sig av copingstrategier.

Fingolimod real world experience

Fingolimod is a Multiple Sclerosis treatment licensed in Europe since 2011. Its efficacy has been demonstrated in three large phase III trials, used in the regulatory submissions throughout the world. As usual, in these trials the inclusion and exclusion criteria were designed to obtain a homogeneous population, with interchangeable characteristics in the different treatment arms. Although this is the best strategy to achieve a robust answer to the investigation question, it does not guaranty the treatment efficacy in the clinical practice, since in the real world there are concomitant treatments, comorbidities, adherence and persistence challenges. But, to make informed treatment decision for a real life patient, we need to have evidence of the treatment efficacy, what has been called treatment effectiveness. This work aims to review fingolimod effectiveness, using as source of information abstracts, posters and manuscripts. This unorthodox strategy was developed because more than half of the published experience with fingolimod is still on abstracts and posters. Only a small part of the studies reviewed are already published in peer reviewed journals. Fingolimod seems to be, at least, as effective and safe as it was on clinical trials, and with its long term experience no new safety signals were observed. In the Portuguese hospital perspective, early treatment with fingolimod is expected to result in better clinical outcomes associated with a more efficient healthcare resources allocation.

Glatiramer Acetate-associated Refractory Immune Thrombocytopenic Purpura

We present a case of glatiramer acetate-associated refractory immune thrombocytopenic purpura (ITP) in a female patient with multiple sclerosis. A search of MEDLINE/PubMed did not find any connection between glatiramer acetate and thrombocytopenia, specifically ITP. The autoimmune reaction was resistant to conservative ITP treatment, and was eventually managed only by splenectomy. To the best of our knowledge, this is the first report of glatiramer acetate-associated ITP. Physicians should be aware of this condition, and consider performing routine blood counts at the beginning of glatiramer acetate treatment.

Spontaneous Cirrhosis Regression in an IFN-beta-induced AIH-like Syndrome Following Drug Withdrawal: Art of Facts or Artifacts?

Autoimmune hepatitis (AIH) is a disease of unknown aetiology with drug-induced AIH being the most complex and not fully understood type. We present the case of a 57-year-old female patient with acute icteric hepatitis after interferon-beta-1b (IFNβ-1b) administration for multiple sclerosis (MS). Based on liver autoimmune serology, histology and appropriate exclusion of other liver diseases, a diagnosis of AIH-related cirrhosis was established. Following discontinuation of IFNβ-1b, a complete resolution of biochemical activity indices was observed and the patient remained untreated on her own decision. However, 3 years later, after a course of intravenous methylprednisolone for MS, a new acute transaminase flare was recorded which subsided again spontaneously after 3 weeks. Liver biopsy and elastography showed significant fibrosis regression (F2 fibrosis). To our knowledge, this is the first report showing spontaneous cirrhosis regression in an IFNβ-1b-induced AIH-like syndrome following drug withdrawal, suggesting that cirrhosis might be reversible if the offending fibrogenic stimulus is withdrawn.

Neurofilaments and NFL-TBS.40-63 peptide penetrate oligodendrocytes through clathrin-dependent endocytosis to promote their growth and survival in vitro.

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