M.Sc.

Die Psychoneuroimmunologie beschäftigt sich unter anderem mit der Frage, ob und unter welchen Bedingungen psychosozialer Stress krank macht. Humanstudien, die dieser Frage nachgehen, können dabei meist nur korrelative Zusammenhänge aufdecken. Um trotzdem Aussagen zu Mechanismen, Ursache-Wirkungsbeziehungen und klinische Relevanz treffen zu können, muss z.B. auf Befunde aus der Tierforschung oder aus in vitro-Studien zurückgegriffen werden. Ziel der vorliegenden Arbeit war es, eine Methode zu finden, welche eine breitere Interpretationsgrundlage für korrelative Befunde aus Humanstudien liefert. Als besonders viel versprechend kann die Untersuchung von Patienten mit Morbus Addison angesehen werden. Patienten mit dieser Erkrankung können aufgrund zerstörter Nebennierenrinden kein Cortisol produzieren. Dieses Fehlen von Cortisol wird medikamentös ausgeglichen. Da bislang keine experimentellen Daten zu den aus der Substitutionstherapie resultierenden freien Cortisolkonzentrationen sowie den endokrinologischen Reaktionen auf Stress vorliegen, wurden in einem ersten Schritt diese beiden Fragestellungen bearbeitet. Anschließend wurde die Methode auf immunologische Fragestellungen angewandt. Die Ergebnisse der durchgeführten Studien zeigen zum einen, dass die medikamentöse Morbus Addison-Therapie in der momentanen Form nicht geeignet ist, den bei Gesunden zu beobachtenden zirkadianen Cortisolrhythmus optimal nachzustellen. Des weiteren bestätigte sich, dass psychosozialer Stress bei Patienten mit Morbus Addison lediglich eine Noradrenalinantwort auslöst, stress-induzierte Anstiege in Cortisol und Adrenalin jedoch ausbleiben. Eine Injektion von 0.03mg/kg Hydrocortison nach einem akuten Stresstest zeigte sich als geeignet, normale stressinduzierte Cortisolanstiege und Maximalwerte nachzustellen. In den untersuchten Immunparametern unterschieden sich gesunde Probanden und Patienten mit Morbus Addison vor Stressinduktion nicht. Stress-bedingte Veränderungen in peripheren Lymphozytenzahlen lassen sich dahingehend interpretieren, dass bei Patienten zwar akut eine Einwanderung von Lymphozyten aus dem Gewebe in das Blut stattfindet, aber Cortisol mitverantwortlich ist für die anschließende Redistribution. Bleibt eine Cortisolstressantwort aus, deutet dieser Befund auf ein erhöhtes Infektionsrisiko hin. Die Verläufe zur stimulierten Produktion des Entzündungsmediators Interleukin-6 stehen im Einklang mit der Hypothese, dass stress-induzierte Cortisolkonzentrationen vor einer überschießenden Entzündungsreaktion schützen. Des weiteren lässt sich bei gesunden Probanden das Absinken der NF-?B-Aktivität nach Stress durch Cortisolwerte direkt nach Stress, bei Morbus Addison-Patienten hingegen durch Veränderungen im Noradrenalin vorhersagen. Das vorliegende Dissertationsprojekt konnte zeigen, dass die Untersuchung von Patienten mit Morbus Addison ein Erfolg versprechender Ansatz ist, um die Gültigkeit von psychoneuroimmunologischen in vitro- und Tierbefunden im intakten menschlichen Organismus zu überprüfen. Die vorliegenden Daten deuten zudem auf eine erstaunliche Anpassungsfähigkeit des Immunsystems hin, was die Notwendigkeit deutlich macht, komplexe psychoneuroimmunologische Prozesse auch im Humanbereich unter Anwendung der Kriterien Hormonsubtraktion und -substitution zu untersuchen. Die Untersuchung von Morbus Addison-Patienten wird in zukünftigen Studien sicherlich entscheidende Hinweise zur klinischen Relevanz einer normalen endokrinen Stressantwort liefern können. / The field of psychoneuroimmunology is among other things dedicated to the question, whether and on what terms psychosocial stress results in disease. Human studies investigating this question often only reveal associations. Consequences regarding mechanisms, causes, and clinical relevance, are thus usually deduced from animal or in vitro studies. The aim of the present thesis was to find an approach, which provides a broader basis for interpretations of correlative findings from human studies. The investigation of patients with Addison´s disease was regarded as the most promising approach. Due to destroyed adrenal glands, these patients are not able to produce cortisol, which therefore has to be substituted. Since no experimental data regarding free cortisol levels resulting from substitution therapy as well as endocrine stress responses are available, in a first step these two question formulations were investigated. Subsequently, this approach was used to investigate two immunological question formulations. The present studies found patients with Addison´s disease to be over-treated. Psychosocial stress resulted in noradrenaline but not in cortisol or adrenaline responses. An injection of 0.03mg/kg hydrocortisone after stress was suitable to induce increases in cortisol levels and cortisol maximums comparable to healthy subjects. Healthy subjects and patients with Addison´s disease did not differ in any baseline immune measures. Stress-induced changes in lymphocyte numbers suggest cortisol being necessary for lymphocyte redistribution subsequent to stress-induced migration into peripheral blood. Without stress-induced cortisol increases, patients are at higher risk for infectious diseases. The trajectories of stimulated interleukin-6 production support the hypothesis of stress-induced cortisol levels protecting the organism against an over-reacting inflammatory immune reaction. Furthermore, in healthy subjects post-stress cortisol levels predicted stress-induced decreases in NF-´B activity, whereas in patients with Addison´s disease noradrenaline predicted such changes. The results of the present thesis supports the assumption of Addison´s disease being a promising approach to test the validity of psychoneuroimmunological in vitro and animal data in human whole organism. Additionally, the present data emphasize the astonishing adaptability of the immune system. This further emphasizes the necessity to investigate psychoneuroimmunological processes utilizing the criteria of hormone subtraction and hormone substitution also in human research. In future studies investigation of patients with Addison´s diseases will certainly provide crucial evidence regarding the clinical relevance of a normal endocrine stress response.

No description available.

Traumatic brain injury (TBI) incidence rates are increasing among the U.S. population and represent substantial acute and chronic care costs. A confounding factor in TBI treatment is the incidence rates of concomitant mental health disorders including depression, anxiety, and posttraumatic stress disorder (PTSD). Clinical data establish that the prevalence of any of these 3 diagnoses complicates the treatment of TBI regardless of whether the diagnosis was pre-existing or occurred because of the TBI, such that prognosis and recovery are negatively impacted. Despite this evidence, psychological assessment is not a first line step in the approach to TBI. The purpose of this research was to assess the prevalence of psychological screening among TBI patients for depression, anxiety, and PTSD to enable conclusions about the current standard of care in TBI management. Meta-analysis of peer reviewed journals on TBI management was used to determine if there was considerable evidence to support that depression, anxiety, and PTSD were being addressed as the standard of care in TBI management. Mean analysis of literature search results established that there was not considerable evidence to support a conclusion that depression, anxiety, and PTSD assessment were standard of care in TBI management. Among the recommendations resulting from this finding were for additional studies on TBI points of care to determine how mental health is currently being managed among TBI patients, and for a change in current TBI treatment protocols to incorporate mental health assessment as part of overall TBI management. If these, and the remaining recommendations, were implemented, it was affirmed that these would have a positive social impact resulting in improved patient outcomes, decreased healthcare costs, and better healthcare delivery for TBI patients.

No description available.

Patients with cancer transitioning from completing their final cancer treatments to survivorship are particularly at risk for experiencing psychosocial stress, and the Institute of Medicine (IOM) has referred to these cancer patients as “lost in transition.” In this study, patients with cancer in their transition phase after completing their final radiation treatment were defined as cancer survivors (CS). CS must deal with chronic stressors such as the fear of cancer recurrence as well as the resumption of their roles in their family and work lives. Chronic stress impacts the nervous system and increases secretion of stress hormones (e.g. cortisol) from the endocrine system, which in turn influences immune function. These systems are particularly relevant for CS since research has shown associations between abnormal cortisol patterns and increased mortality in breast CS and immune dysfunction in CS can increase susceptibility to infections. The theoretical framework of psychoneuroimmunology (PNI), which describes the interactions between the psychosocial, neuroendocrine and immune systems, guided the choice of outcomes for this study. The IOM has identified a lack of theory-driven interventions for managing psychosocial stress in CS. We reviewed the literature and identified two major types of PNI-based psychosocial interventions for cancer patients, namely cognitive-behavioral and complementary medical. One promising brief and inexpensive psychosocial intervention was expressive writing, which involved participants disclosing their deepest thoughts and feelings regarding their cancer in four 20-30 minute writing sessions over four consecutive days. We conducted a two-arm randomized controlled trial to determine the efficacy of an online expressive writing (EW) intervention delivered to CS who were 2-12 months post-radiation treatment completion. The results of this study revealed that EW was effective in regulating stress in our sample of CS over a period of six weeks as measured by lowered salivary cortisol levels and lowered self-reported fear of cancer recurrence. Online EW is a low-cost and convenient approach for delivering stress-management interventions for CS during survivorship. However, coordinated efforts are needed from health researchers, professionals and policy makers to define standardized approaches for testing psychosocial interventions and using PNI biomarkers to help develop evidence-based psychosocial cancer-care for CS during survivorship.

O câncer e o processo de hospitalização comumente cursam com forte impacto psicológico sobre as crianças e adolescentes, gerando estresse e fadiga. Isto aplica-se especialmente, para àqueles sob quimioterapia, pois esta, constitui-se em uma das experiências mais estressantes e ameaçadoras que pode exacerbar os sintomas relacionados ao câncer e levar a uma diminuição da qualidade de vida (QV). O estresse associado ao desenvolvimento do câncer pode causar disrupturas no eixo hipotálamo-hipófise-adrenal, e suprimir importantes vias neuroimunoendócrinas. Assim, intervenções destinadas a atenuar as alterações fisiológicas relacionadas ao estresse podem favorecer a recuperação do sistema imune e induzir alterações neuroimunoendócrinas para potencializar a vigilância imunológica durante o tratamento oncológico. Com o aumento da incidência de câncer, é crucial que os profissionais de saúde desenvolvam intervenções eficazes para o manejo dos sintomas oncológicos, de modo a aliviar a sobrecarga do tratamento nesses pacientes durante o processo de hospitalização, de modo a contribuir para um melhor prognóstico da doença. Ademais, pacientes pediátricos oncológicos podem se beneficiar de intervenções não-farmacológicas, por exemplo, a intervenção dos clowns, para aliviar os sintomas relacionados ao câncer. Contudo, poucos estudos têm investigado os mecanismos moleculares envolvendo a intervenção dos clowns. Nosso objetivo principal foi investigar os efeitos da intervenção dos clowns sobre o estresse psicológico e a fadiga-relacionada ao câncer (FRC) em pacientes pediátricos oncológicos sob quimioterapia. Além disso, nós investigamos se alterações nos níveis de cortisol, ?-amilase (sAA), citocinas e metaloproteinases de matriz (MMP-9) estão associadas com estresse psicológico e com FRC de pacientes pediátricos com osteossarcoma submetidos à intervenção dos clowns. Trata-se de um estudo quase-experimental pré-teste/pós-teste. Foram colhidas oito amostras de saliva em momentos idênticos, isto é, no baseline (pré-intervenção) e no pós-intervenção (+ 1h, + 4h, + 9h e + 13h após o despertar). As concentrações de cortisol salivar, sAA, citocinas e MMP-9 foram mensuradas por ELISA. Dados sociodemográficos e clínicos foram coletados via prontuários médicos, além disso, foram aplicadas a Escala de Estresse Infantil-ESI(TM) e a Escala Multidimensional de Fadiga-PedsQL(TM). Os escores das escalas foram comparados entre o baseline e o pós-intervenção, e também, foram correlacionados com os níveis dos biomarcadores. Para análise dos dados, utilizou-se da estatística descritiva e estatística não paramétrica. Em comparação com as medidas do baseline, observamos que os níveis de estresse psicológico total, bem como os de fadiga geral dos pacientes pediátricos oncológicos, melhoraram significativamente após a intervenção dos clowns ( p= 0.003; p= 0.049, respectivamente). Não houve correlações significativas entre as Áreas sob Curva (AUC) da sAA e do cortisol no baseline e nem no pós-intervenção. Além disso, a intervenção dos clowns reduziu os níveis de IL-1? e de cortisol nos pacientes pediátricos com osteossarcoma. A AUC da IL-1? correlacionou-se positivamente com AUC do cortisol e com a AUC da sAA no pósintervenção. Inversamente, os níveis de IL-6, TNF-?, IL-12p70, IL-10, TGF-? e MMP-9 não mostraram diferenças significativas no pós-intervenção. Em síntese, nossos resultados sugerem que a intervenção dos clowns é uma boa intervenção não-farmacológica para reduzir o estresse psicológico e a FRC em pacientes pediátricos oncológicos sob quimioterapia / Cancer and the hospitalization process often have a psychological impact on the children and adolescents, usually leading to intense stress as well as fatigue. This especially applies to children and adolescents who have been submitted to chemotherapy, since it still constitutes a stressful and threatening experience for them and may exacerbate cancer symptom burden clusters, leading to a decrease in their health related quality of life (QoL). In addition, stress associated with cancer development leads to disturbances/disruption in the hypothalamicpituitary-adrenal (HPA) axis and suppresses important neuroimmunoendocrine pathways. Hence, interventions aimed at attenuating the physiological changes related to stress favor the recovery of the immune system and, consequently, induce alterations in neuroimmunoendocrine factors that increase immunological surveillance during cancer treatment. With the increase in cancer rates, it is crucial that healthcare professionals develop effective interventions to support pediatric cancer patients during the hospitalization process in order to relieve the burden of cancer treatment, which may contribute to a better prognosis of the disease. In an attempt to alleviate some of the cancer-related symptoms, pediatric oncology patients can take advantage of non-pharmacological interventions, including clown intervention, which can be a very advantageous approach to reduce unpleasant symptoms in pediatric cancer patients. However, few studies have investigated the molecular mechanisms that mediate health outcomes of clown intervention. The main purpose of this study was to investigate the effects of the clown intervention on psychological stress and cancer-related fatigue (CRF) in pediatric cancer inpatients undergoing chemotherapy. Also, we aimed to investigate whether changes in the levels of biomarkers, including cortisol, ?-amylase (sAA), cytokines, and matrix metalloproteinase-9 (MMP-9) are associated with psychological stress and CRF levels in pediatric osteosarcoma inpatients following clown intervention. A pretestposttest quasi-experimental study was undertaken with pediatric cancer inpatients. Eight nonfasting saliva samples were collected at identical times upon clown intervention, i.e., at baseline (pre-intervention) and post-intervention (+ 1h, + 4h, + 9h, and + 13h post awakening). Salivary cortisol, sAA, cytokines and MMP-9 concentrations were measured using high sensitivity Enzyme-Linked Immuno Sorbent Assay. Sociodemographic and clinical data, and Child Stress Scale-ESI(TM) and PedsQL(TM) Multidimensional Fatigue Scale were applied and the results were compared at baseline and after the clown intervention, and also correlated with biomarker trajectories. Data analysis was performed using nonparametric statistical tests. In comparison with baseline measurements, the overall psychological stress for pediatric cancer inpatients as well as their perception of fatigue improved upon clown intervention (p= 0.003; p= 0.049, respectively). There were no significant correlations between sAA and cortisol for both Areas Under Curve (AUC) at baseline or at post-intervention. Also, clown intervention reduced IL1? and salivary cortisol levels in pediatric osteosarcoma inpatients. Additionally, AUC for IL1? positively correlated with AUC for cortisol as well as with AUC for sAA at postintervention. In contrast, levels of IL-6, TNF-?, IL-12p70, IL-10, TGF-? and MMP-9 did not show significant differences upon clown intervention. Overall, our results suggest that clown intervention is a good non-pharmacological intervention to reduce psychological stress and CRF in pediatric cancer inpatients undergoing chemotherapy

published_or_final_version / Architecture / Master / Master of Architecture

This study maps research concerning person environment interrelationships with health and wellbeing outcomes. The purpose of this study is to provide insights into the inter-relationship between the built environment (BE) and human health and wellbeing as it is conveyed in research literature. It particularly focuses on literature that connects built environment, emotions, feelings, mind and body. This thesis therefore provides a review of relevant literature on the physical environment, with a focus on person environment (PE) relationship that may influence the person's psychological and physiological systems consequently affecting health and wellbeing. Specifically, psychoneuroimmunology (PNI) is used to identify dimensions of the BE which are significant for this study. The understanding of PE interrelationships to health outcomes is achieved by undertaking a transdisciplinary outlook. To conceptualise the 'person' as a whole and the workings of the mind and human system PNI has been recognised as a main platform. PNI is the study of mind-body relationships (Evans, et al, 2000), providing a scientific framework which captures the understanding of the inter-relationship of the mind to the neuroendocrine systems and the immune systems with the aim of understanding the influence of the mind on eliciting as well as preventing illnesses. The work was motivated by the need for better understanding of the human interaction/transaction in an interior environment and their consequences on health. An exploration of literature from both the environmental and health fields provided a knowledge base upon which to develop an understanding of the interrelationship. Research has demonstrated a link between the BE and wellbeing, however, this is limited in its application and/or scope. For example, over the past years there has been an increasing amount of research showing the possible influence of the environment in reducing stress (Sommer & Oslen, 1980; Kaplan, 1983; O'Neill, 1991; Wapner & Demick, 2000; Parsons & Tassinary, 2002, Frumkin, 2006). In addition, there is growing evidence that indicates there is a relationship between BE and health including the psychological and physiological systems, in healthcare environments (Ulrich & Zimring, 2004). However, while there is ample research in the areas of environmental stressors and other determinants of the environment in contributing to health, less research has been undertaken in studying the impact of the environment on health (Evans& McCoy, 1998). The potential of the environment in contributing to the mental wellbeing of a person and how this could affect the physical health therefore needs further investigation (Solomon, 1996). The methodology followed was Coopers (1998) 'research synthesis' and the tool to sort the domains and PE interrelationships was adapted from White's (1989) 'space adjacency analysis'. The scope of this study was limited to explorations of literature that inquired into PE relationships that fit into the primarily established 'integrative systems model'; a parameter that enabled categorisation of the literature into the areas that related to the PNI framework. The findings illustrate that the person is interrelated to the environment in several ways and can be interpreted and explained in terms of various dimensions such as the psychological, physical, social, and spatial dimensions. Furthermore, empirical research indicates that the environment impacts on a person's health and wellbeing through psychological and physiological systems. PNI acknowledges the interrelationship of the mind and body systems contributing to an integrative systems model of human health and wellbeing. As an outcome, the study has produced an analysis method and a navigation map of the various literature domains related to PE interrelationships in terms of health and wellbeing. This has been facilitated by the development of, a 'PE integrative systems model'. Apart from demonstrating the need for transdisciplinary research and contributing to research methodology, the study also adds to the current design knowledge base providing BE professionals and creators with a better understanding of the health outcomes from PE interrelationships.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-08-18T15:15:06Z No. of bitstreams: 1 lucamjustodemoraes.pdf: 3288848 bytes, checksum: b08a4dcf158a0f9384a1bd0f7fbe1f3e (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-08-24T12:02:04Z (GMT) No. of bitstreams: 1 lucamjustodemoraes.pdf: 3288848 bytes, checksum: b08a4dcf158a0f9384a1bd0f7fbe1f3e (MD5) / Made available in DSpace on 2017-08-24T12:02:04Z (GMT). No. of bitstreams: 1 lucamjustodemoraes.pdf: 3288848 bytes, checksum: b08a4dcf158a0f9384a1bd0f7fbe1f3e (MD5) Previous issue date: 2017-02-21 / Psiconeuroimunologia é definida como o estudo da interação entre comportamento, mecanismos neuroendócrinos e processos imunológicos. Evidências têm apontado a correlação entre comportamento e fatores psicossociais tais como sintomas depressivos, ansiedade, estresse, qualidade de vida, religiosidade/espiritualidade (R/E), bem como mecanismos neuroendócrinos, imunológicos e a progressão do HIV/AIDS. O objetivo desta pesquisa foi investigar possíveis associações entre variáveis psicossociais, níveis de linfócitos T CD4 e carga viral em portadores do HIV, visando destacar fatores de natureza emocional, comportamental e sociais promotores de imunossupressão e replicação viral numa amostra de 197 participantes diagnosticados com HIV/AIDS. Os participantes foram selecionados no programa público para tratamento de doenças sexualmente transmissíveis de Juiz de Fora/MG (Brasil) e deveriam estar fazendo uso da medicação antirretroviral há no mínimo seis meses. Os participantes foram divididos em dois grupos de acordo com o nível de linfócitos T CD4: Grupo A (CD4 > 500) e Grupo B (CD4 ≤ 500). Foram investigadas as diferenças entre os grupos nos níveis de depressão, ansiedade, estresse, aspectos religiosos/espirituais, qualidade de vida e carga viral. Os dados foram tabulados e submetidos às análises de Odds Ratio entre variáveis categóricas e quadro de AIDS, bem como a análises de diferenças entre os grupos (teste Mann Whitney) e análises de correlação (ρ de Spearman e r de Pearson). Resultados principais apontaram correlações positivas significativas entre as variáveis comprometimento R/E e tempo de convívio com HIV (ρ = 0.338; p = 0.05), comprometimento R/E e idade (ρ = 0.310; p = 0.04), e entre autoavaliação R/E e tempo de convívio com HIV (ρ = 0.409, p = 0.01). Correlações negativas significativas foram verificadas entre experiências espirituais diárias e carga viral (ρ = - 0.287; p = 0.06), e entre valores e crenças R/E e CD4 (ρ = - 0.326; p = 0.03). Conclui-se que variáveis R/E tais como comprometimento R/E, autoavaliação R/E, experiências espirituais diárias e valores e crenças R/E podem estar associadas a alterações nos níveis de linfócitos T CD4 e carga viral entre portadores do HIV. Tais evidências apontam para a pertinência no que diz respeito a futuras investigações científicas sobre possíveis relações recíprocas entre aspectos religiosos/espirituais e progressão da infecção por HIV/AIDS. / Psychoneuroimmunology has been defined as the study about the interaction between behavior, neuroendocrine mechanisms and immunological processes. Different evidences have pointed correlations between behavior and psychosocial factors such as depression, anxiety, stress, quality of life, religiosity/spirituality, neuroendocrine mechanisms, immunological system and changes in HIV/AIDS progression. The aim of the present study was to explore the association between psychosocial variables, lymphocytes T CD4 levels, and viral load in a population of HIV seropositive, emphasizing the emotional, behavioral and social factors associated with immunosuppression and viral replication. The sample consisted of 197 HIV seropositive, attending a public program of sexuality transmitted diseases of Juiz de Fora/MG (Brazil) taking antiretroviral medicine for at least six months. Participants were divided in 2 groups: Group A (CD4 > 500) and Group B (CD4 ≤ 500). Levels of depression, anxiety, stress, quality of life, religious and spiritual aspects, CD4 T lymphocytes and viral load were compared. Data were tabulated and analyzed applying different statistical strategies: Odds Ratio between categorical variables and AIDS diagnosis, analyses of the differences between groups (Mann Whitney test), and analyses to verify the correlation between continuous variables (ρ de Spearman e r de Pearson). Key results pointed significant positive correlations between the variables of R/E commitment and living with HIV (ρ = 0.338; p = 0.05), R/E commitment and age (ρ = 0.310; p = 0.04), R/E self-assessment and living with HIV (ρ = 0.409, p = 0.01). And significant negative correlations between daily spiritual experiences and viral load (ρ = - 0.287; p = 0.06), R/E values and beliefs and CD4 (ρ = - 0.326; p = 0.03). In general, our results pointed that religious/spiritual variables such as R/E commitment, R/E self-assessment, daily spiritual experiences, and R/E values and beliefs, might be associated with changes in lymphocytes T CD4 and viral load levels among HIV seropositive people. These evidences indicate the relevance of future scientific investigations about possible reciprocal relations between religious/spiritual aspects and HIV/AIDS disease progression.