Developmental-like responses in injured mature central neurons

Traumatic insults to the central nervous system are frequently followed by profound and irreversible neuronal loss as well as the inability of the damaged neurons to regenerate. One of the major therapeutic challenges is to increase the amount of surviving neurons after trauma. Thus it is crucial to understand how injury affects neuronal responses and which conditions are optimal for survival to prevent neuronal loss. During development neuronal survival is thought to be dependent on the competition for the availability of survival-promoting molecules called neurotrophic factors. Much less is known on the survival mechanisms of mature neurons under traumatic conditions. Increasing amount of evidence points towards the possibility that after injury neuronal responses might aquire some developmental characteristics. One of the important examples is the change in the responses to the neurotransmitter GABA: it is inhibitory in the intact mature neurons, but can induce excitation during development and after trauma. An important step in the maturation of GABAergic transmission in the CNS is the developmental shift in the action of GABAA receptor from depolarization in immature neurons to hyperpolarization in mature neurons. GABAA-mediated responses are tightly linked to the homeostasis of the chloride anion (Cl-), which in neurons is mainly regulated by Na+-K+-2Cl- cotransporter NKCC1 and K+-Cl- cotransporter KCC2. Trauma-induced functional downregulation of KCC2 promotes a shift from hyperpolarizing GABAA-mediated responses to depolarizing. Other important consequences of neuronal trauma are the emergence of dependency of central neurons on brain-derived neuro¬trophic factor (BDNF) for survival, as well as the upregulation of neurotrophin receptor p75NTR. Our aim was to answer the question whether these post-traumatic events are interrelated, and whether the regulation of BDNF and KCC2 expression is different under traumatic conditions and in intact neurons. To study responses of injured mature central neurons, we used an in vitro and in vivo axotomy models. For in vitro studies, we lesioned organotypic hippocampal slices between CA3 and CA1 regions, which resulted in selective axotomy of the CA3 neurons and denervation of the CA1 neurons. Some experiments were repeated in vivo by lesioning the neurons of the corticospinal tract at the internal capsule level, or by lesioning spinal motoneurons at the ventral root. We show that intact mature neurons do not require BDNF for survival, whereas in axotomized neurons apoptosis is induced upon BDNF deprivation. We further show that post-traumatic dependency on BDNF is mediated by injury-induced upregulation of p75NTR. Post-traumatic increase in p75NTR is induced by GABAA-mediated depolarization, consequent opening of voltage-gated Ca2+ channels, and the activation of Rho kinase ROCK. Thus, post-traumatic KCC2 downregulation leads to the dependency on BDNF through the induction of p75NTR upregulation. Neurons that survive after axotomy over longer period of time lose BDNF dependency and regain normal KCC2 levels. This phenomenon is promoted by BDNF itself, since after axotomy contrary to normal conditions KCC2 is upregulated by BDNF. The developmentally important thyroid hormone thyroxin regulates BDNF expression during development. We show that in mature intact neurons thyroxin downregulates BDNF, whereas after axotomy thyroxin upregulates BDNF. The elevation of BDNF expression by thyroxin promoted survival of injured neurons. In addition, thyroxin also enhanced axonal regeneration and promoted the regaining of normal levels of KCC2. Thus we show that this hormone acts at several levels on the axotomy-initiated chain of events described in the present work, and could be a potential therapeutic agent for the injured neurons. We have also characterized a previously unknown downregulatory interaction between thyroxin and KCC2 in intact neurons. In conclusion, we identified several important interactions at the neurotrophin-protein and hormone-neurotrophin level that acquire immature-like characteristics after axotomy and elucidated an important part of the mechanism by which axotomy leads to the requirement of BDNF trophic support. Based on these findings, we propose a new potential therapeutic strategy where developmentally crucial agents could be used to enhance survival and regeneration of axotomized mature central neurons.

Analysis of residual tropical cemented soil behaviour

In -situ soils in gee-material spectrum might arise due to sedimentation or could be non-sedimentary residual formations. The inherent nature and diversity of geological processes involved in the soil formation stage itself are responsible for a wide variability in the in-situ state of the soil. In this paper the possibility of analyses to arrive at engineering parameters of residual soils with varied degrees of residual or acquired cementation by the use of physical and in-situ parameters normally determined in routine investigations, are examined. An Intrinsic State Line,(ISL), with reference to an intrinsic state parameter (e/e(L)) and its variation with effective stress for reconstituted clays has been developed for residual tropical soils of non-sedimentary origin. In relation to the Intrinsic State Line (ISL), the undisturbed state, e, the potential parameter, e(L), along with the overburden pressure data has been analyzed to identify the dominance of cementation or stress history or both in controlling the compressibility and strength behaviour of natural residual soil. The location of yield stress point in relation to the ISL, pre-, and post- yield stress, compression indices along the e- log sigma(v) path provide a simple means to the analysis of the compressibility characteristics of cemented soils for analysis.

Stimuli-responsive colorimetric and NIR fluorescence combination probe for selective reporting of cellular hydrogen peroxide

Hydrogen peroxide (H2O2) is a key reactive oxygen species and a messenger in cellular signal transduction apart from playing a vital role in many biological processes in living organisms. In this article, we present phenyl boronic acid-functionalized quinone-cyanine (QCy-BA) in combination with AT-rich DNA (exogenous or endogenous cellular DNA), i.e., QCy-BA subset of DNA as a stimuli-responsive NIR fluorescence probe for measuring in vitro levels of H2O2. In response to cellular H2O2 stimulus, QCy-BA converts into QCy-DT, a one-donor-two-acceptor (D2A) system that exhibits switch-on NIR fluorescence upon binding to the DNA minor groove. Fluorescence studies on the combination probe QCy-BA subset of DNA showed strong NIR fluorescence selectively in the presence of H2O2. Furthermore, glucose oxidase (GOx) assay confirmed the high efficiency of the combination probe QCy-BA subset of DNA for probing H2O2 generated in situ through GOx-mediated glucose oxidation. Quantitative analysis through fluorescence plate reader, flow cytometry and live imaging approaches showed that QCy-BA is a promising probe to detect the normal as well as elevated levels of H2O2 produced by EGF/Nox pathways and post-genotoxic stress in both primary and senescent cells. Overall, QCy-BA, in combination with exogenous or cellular DNA, is a versatile probe to quantify and image H2O2 in normal and disease-associated cells.

¿Perspectiva médica o visión integral del hombre? : análisis crítico de la anticoncepción

Resumen: El objetivo principal de este trabajo es analizar si la anticoncepción es un asunto perteneciente a la Medicina, como lo indica la práctica, o si merece una visión bajo una perspectiva más amplia. Se analizan publicaciones que estudian el problema de la efectividad de la anticoncepción considerando variables demográficas, económicas y sociales que gravitan a la hora de evaluar la eficacia en anticoncepción. Se incluye en el análisis aspectos espirituales y psicológicos, que generalmente son subestimados, pero que fueron considerados en el pensamiento filosófico y antropológico que desplegó K. Wojtyla, quien parte de la base de la unidad de la persona

Um certo olhar sobre a velhice : a narrativa memorialista de Pedro Nava

Este trabalho tem como objetivo investigar as transformações do envelhecimento que se dão pelas narrativas produzidas pelas lembranças. Busca destacar a especificidade do papel da memória no processo de envelhecimento e a sua força de transformação e resistência. A pertinência do tema está ligada a marcada expressão que o contingente de pessoas idosas adquiriu nos anos recentes ao ganhar visibilidade cada vez maior, impondo-se como um grupo com demandas e características próprias. No estudo, articulam-se os conceitos de sujeito, de memória e de narratividade. Na primeira parte, desenvolve-se a noção de sujeito, desde um eu central, fundamento de uma unidade de expressão, até a fragmentação desse eu, que se torna múltitiplo e expressão crítica do homem moderno. Na segunda parte, o estudo da memória, acompanhamos a passagem de uma memória definida como permanente e reprodutora para uma descrição de memória como uma habilidade criativa, capaz de retrospectivamente produzir novas narrativas. Na terceira parte, estudamos o conceito de narratividade, explorando diversos aspectos para além do campo literário. Finalmente, com a rede conceitual sujeito - memória - narrativa estabelecida, reconhecemos na obra de Pedro Nava o surgimento de múltiplos narradores, que, frente a velhice, em vez de se defender e negar a vida, aceitam o desafio de um confronto e se afirmam, forjados em suas diferenças.

Paixões e afetos: possibilidades de leitura das teses da Faculdade de Medicina do Rio de Janeiro no século XIX

Este trabalho busca investigar as condições de produção dos saberes psicológicos contidos nas teses de doutoramento da Faculdade de Medicina do Rio de Janeiro no século XIX. Tal meta visa, a partir de conceitos diversos, obter os princípios norteadores das obras dos futuros doutores, tomando como ponto de partida o seu contexto sócio-cultural. Dois conceitos, no entanto, serão privilegiados: os de paixão e afeto. Estes são conceitos que surgem em diversas teses, principalmente naquelas da primeira metade do séulo XIX período da maior parte das teses selecionadas nesta ocasião. Uma das principais questões levantadas diz respeito à maneira como os autores das teses elaboram seus trabalhos: utilizam-se das mais diversas referências para que possam corroborar aquilo que propõem em seus trabalhos. Assim, freqüentemente recorrem a textos de autores consagrados mesmo que, por vezes, não haja concordância entre os autores escolhidos. Os conteúdos utilizados são díspares, mas, como são aparentemente concordantes com o que os médicos produzem, são apropriados por estes. Esta apropriação vem a ser discutida a partir do trabalho de Michel de Certeau. Também vemos alguns elementos das teses sofrerem transformações, num trabalho de bricolagem, tal como propõe Claude Lévi-Strauss. É inegável que a apropriação e a bricolagem vão além do que se verifica nas obras de Certeau e Lévi-Strauss: estes se referem à cultura popular quando tratam daqueles temas, mas ao fazer uma incursão pelos escritos das teses, pode-se perceber que os mesmos fenômenos são característicos também de materiais que estão além do que geralmente se chama de cultura popular, haja vista que teses de medicina não poderiam ser interpretadas como tal. Sendo o período pesquisado uma época em que a psicologia ainda não se constituiu como ciência, os trabalhos médicos tornam-se instrumentos privilegiados de difusão de saberes psicológicos. Fazem parte de um material que impulsiona a produção de conhecimento sobre o homem em seus aspectos individuais, culturais, sociais, psicológicos, indo além das discussões fisiológicas e orgânicas. Embora estas estejam presentes, formam um conjunto com o qual os autores das teses buscam verificar as vicissitudes humanas. Para realizar este estudo foi necessária uma pesquisa documental, onde as teses servem como fontes primárias para a execução do trabalho. Através da análise dos temas e termos constantes das teses, pretende-se constituir um mapa sobre o qual torna-se possível articular as idéias veiculadas nas teses com o contexto sócio-cultural em que são produzidos os materiais dos escritos dos médicos

Existências enclausuradas na era da técnica

O fenômeno da compulsão vem sendo amplamente discutido no terreno da psicologia, principalmente, pela apropriação de um discurso técnico-cientificista que, de forma dominante, compreende a experiência da compulsão como um desvio oriundo ora da interioridade humana, privilegiando, assim, aspectos de ordem biológica ou psíquica; ora da exterioridade, enfatizando o mundo como determinante dos comportamentos humanos. Essa visão dicotomizada sobre o homem pode ser compreendida como uma tentativa constante na história da psicologia de reafirmar o campo das experiências humanas através do embate de perspectivas herdadas da tradição científica moderna, ainda, fortemente, presente no campo das ciências humanas. Atentando para essas considerações, este estudo traz como proposta pensar o fenômeno da compulsão e suas diferentes expressões a partir de um referencial outro que não o da tradição dominante da psicologia. Para tanto, encontramos no pensamento fenomenológico-hermenêutico de Martin Heidegger, fundamentos para se pensar homem e mundo não como instâncias separadas que tratariam posteriormente de recobrar seus vínculos, mas sim como uma relação co-originária, na qual ambos formam uma unidade copertencente, e inviabilizando, assim, uma interpretação do homem fora dos contornos de seu horizonte histórico. Horizonte esse, que, segundo Heidegger, desvela-se ao modo da técnica. Dessa forma, vemos um mundo permeado por solicitações de utilidade, produtividade, exploração e controle, que nos possibilita compreender que é no horizonte da técnica que a compulsão se apresenta como um dos modos de ser dominantes do homem, não podendo este e seus sofrimentos existenciais serem compreendidos desarticulados desse mesmo horizonte.

Enhanced contextual fear memory in central serotonin-deficient mice

Central serotonin (5-HT) dysregulation contributes to the susceptibility for mental disorders, including depression, anxiety, and posttraumatic stress disorder, and learning and memory deficits. We report that the formation of hippocampus-dependent spatia

Sexual Behavior Modulates Contextual Fear Memory Through Dopamine D1/D5 Receptors

Traumatic events always lead to aversive emotional memory, i.e., fear memory. In contrast, positive events in daily life such as sex experiences seem to reduce aversive memory after aversive events. Thus, we hypothesized that post-traumatic pleasurable ex

Effects of shear band propagation on submarine landslide

Interbedded layers of glacial deposits and marine or glacimarine clay layers are a common feature of offshore sediment. Typically, offshore marine clays are lightly overconsolidated sensitive clay. Some case histories on submarine landslides show that the slip surface passes through these marine clay layers. In this paper a model is proposed for post-peak strain softening behavior of marine sensitive clay. The slope failure mechanism is examined using the concept of shear band propagation. It is shown that shear band propagation and post-peak stress-strain behavior of clay layers are two major factors in submarine slope stability analysis. Copyright © 2012 by the International Society of Offshore and Polar Engineers (ISOPE).

Women's help seeking behaviour and the associated influencing factors on self discovery of a breast symptom

To investigate women’s help seeking behavior (HSB) following self discovery of a breast symptom and determine the associated influencing factors. A descriptive correlation design was used to ascertain the help seeking behavior (HSB) and the associated influencing factors of a sample of women (n = 449) with self discovered breast symptoms. The study was guided by the ‘Help Seeking Behaviour and Influencing Factors” conceptual framework (Facione et al., 2002; Meechan et al., 2003, 2002; Leventhal, Brissette and Leventhal, 2003 and O’Mahony and Hegarty, 2009b). Data was collected using a researcher developed multi-scale questionnaire package to ascertain women’s help seeking behavior on self discovery of a breast symptom and determine the factors most associated with HSB. Factors examined include: socio-demographics, knowledge and beliefs (regarding breast symptom; breast changes associated with breast cancer; use of alternative help seeking behaviours and presence or absence of a family history of breast cancer),emotional responses, social factors, health seeking habits and health service system utilization and help seeking behavior. A convenience sample (n = 449 was obtained by the researcher from amongst women attending the breast clinics of two large urban hospitals within the Republic of Ireland. All participants had self-discovered breast symptoms and no previous history of breast cancer. The study identified that while the majority of women (69.9%; n=314) sought help within one month, 30.1% (n=135) delayed help seeking for more than one month following self discovery of their breast symptom. The factors most significantly associated with HSB were the presenting symptom of ‘nipple indrawn/changes’ (p = 0.005), ‘ignoring the symptom and hoping it would go away’ (p < 0.001), the emotional response of being ‘afraid@ on symptom discovery (p = 0.005) and the perception/belief in longer symptom duration (p = 0.023). It was found that women who presented with an indrawn/changed nipple were more likely to delay (OR = 4.81) as were women who ‘ignored the symptoms and hoped it would go away’ (OR = 10.717). Additionally, the longer women perceived that their symptom would last, they more likely they were to delay (OR = 1.18). Conversely, being afraid following symptom discovery was associated with less delay (OR = 0.37; p=0.005). This study provides further insight into the HSB of women who self discovered breast symptoms. It highlights the complexity of the help seeking process, indicating that is not a linear event but is influenced by multiple factors which can have a significant impact on the outcomes in terms of whether women delay or seek help promptly. The study further demonstrates that delayed HSB persists amongst women with self discovered breast symptoms. This has important implications for continued emphasis on the promotion of breast awareness, prompt help seeking for self discovered breast symptoms and early detection and treatment of breast cancer, amongst women of all ages.

The psychology of immersion and development of a quantitative measure of immersive response in games

This study sets out to investigate the psychology of immersion and the immersive response of individuals in relation to video and computer games. Initially, an exhaustive review of literature is presented, including research into games, player demographics, personality and identity. Play in traditional psychology is also reviewed, as well as previous research into immersion and attempts to define and measure this construct. An online qualitative study was carried out (N=38), and data was analysed using content analysis. A definition of immersion emerged, as well as a classification of two separate types of immersion, namely, vicarious immersion and visceral immersion. A survey study (N=217) verified the discrete nature of these categories and rejected the null hypothesis that there was no difference between individuals' interpretations of vicarious and visceral immersion. The primary aim of this research was to create a quantitative instrument which measures the immersive response as experienced by the player in a single game session. The IMX Questionnaire was developed using data from the initial qualitative study and quantitative survey. Exploratory Factor Analysis was carried out on data from 300 participants for the IMX Version 1, and Confirmatory Factor Analysis was conducted on data from 380 participants on the IMX Version 2. IMX Version 3 was developed from the results of these analyses. This questionnaire was found to have high internal consistency reliability and validity.

Symptom burden in individuals with inflammatory bowel disease: a mixed methods study

To investigate the symptom burden experiences of individuals with inflammatory bowel disease (IBD). An explanatory sequential mixed methods study was conducted. A cross-sectional, correlational survey was first undertaken. Symptom burden was measured using a modified disease specific version of the Memorial Symptom Assessment Scale, which was administered to a consecutive sample of individuals with IBD (n = 247) at an IBD Outpatients department in one urban teaching hospital in Ireland. Disease activity was determined using clinical disease activity indices, which were completed by the consulting physician. A sequential qualitative, descriptive study was then conducted aimed at explaining noteworthy quantitative findings. A criterion-related purposeful sample of seven participants from the quantitative study was recruited. Semi-structured face to face interviews were conducted using an interview guide and data were analysed using content analysis. Findings revealed that participants experienced a median of 10 symptoms during the last week, however as many as 16 symptoms were experienced during active disease. The most burdensome symptoms were lack of energy, bowel urgency, diarrhoea, feeling bloated, flatulence and worry. Total symptom burden was found to be low with a mean score of 0.56 identified out of a possible range from 0 to 4. Participants with active disease (M = 0.81, SD = 0.48; n = 68) had almost double mean total symptom burden scores than participants with inactive disease (M = 0.46, SD = 0.43; n = 166) (p < 0.001). Mean total psychological symptom burden was found to be significantly greater than mean total physical symptom burden (rho = 0.73, n = 247, p < 0.001). Self-reported disease control, gender, number of flare ups in the last two years, and smoking status was found to be significant predictors of total symptom burden, with self-reported disease control identified as the strongest predictor. Qualitative data revealed tiredness, pain, bowel symptoms, worry and fear as being burdensome. Furthermore, symptom burden experiences were described in terms of its impact on restricting aspects of daily activities, which accumulated into restrictions on general life events. Psychological symptom burden was revealed as more problematic than physical symptom burden due to its constant nature, with physical and psychological symptoms described to occur in a cyclical manner. Participants revealed that disease control was evaluated not only in terms of symptoms, but also in terms of their abilities to control the impact of symptoms on their lives. This study highlights the considerable number of symptoms and the most burdensome symptoms experienced by individuals with IBD, both during active and inactive disease. This study has important implications on symptom assessment in terms of the need to encompass both physical and psychological symptoms. In addition, greater attention needs to be placed on psychological aspects of IBD care.

Inquiring into perspective transformation in university education

My Portfolio of Exploration tackles the difficult question as to whether adult mental development can be accelerated and if so how. Rooted in constructive-developmental ideas, adult mental development is explained as an evolutionary unfolding of human capability. Going beyond this I look at the possibility of advancing development as transformational growth in adulthood in the belief that a broader perspective leads to increased effectiveness in professional life. Initially I explored my own meaning making, to make sense of my experiences, knowledge, relationships and my own motivations. This exploration has provided me with a ‘developmental bridge’ between my current way of knowing and a new more enlightened way. I have come to view my way of making meaning in the world as an evolving and progressive sequence of emotional and cognitive development. Through the formation of new stretching experiences, increased self - awareness and reflection my previous perspective has been overtaken by a more complex form of being aware of myself, others and the world. I refer to this process of growth as transformation. As part of my own transformational work I have conducted an inquiry into transformational growth and learning in the early academic life of university undergraduates. The result shows how accelerated adult mental development can be achieved in an academic environment ably preparing students for the workplace. This new model of education is part of a truly unique and exciting model signalling ground-breaking change for the undergraduate experience. The overhaul of a traditional BA degree in Economics into a world-class transformational programme is discussed through-out my Portfolio. Central to my broadening awareness is the challenge and nurturing required to awaken the student’s ‘internal authority’ . This involves stimulating students to take ownership for their own thinking, steering them away from the passivity and complacency of thinking through the minds of others. In doing so, the ultimate aim of renewing the BA is to narrow the developmental ‘mismatch’ which exists for m any college students between them and the world of work, by encouraging and inviting them to take on the challenge of thinking independently. Mindfulness, awareness, and personal authority are treated with reverence throughout the exploration as I consider them core parts of the students engaging with development. Engagement is construed as an active and open-minded process of awareness involving planning and reviewing one’s own goals and performance, engaging in constructive feedback, reflection and new action. I conclude with a view that the journey of adult mental development is relentless and that undergraduate education represents a crucial beginning. The value and relevance of transformational education rooted in developmental principles provides a significant opportunity in advancing development and perspectives at the start of adult life.

The political and economic context of Keynes’s 1933 Finlay lecture: transforming a business practitioner’s ways of knowing

This thesis is structured in the format of a three part Portfolio of Exploration to facilitate transformation in my ways of knowing to enhance an experienced business practitioner’s capabilities and effectiveness. A key factor in my ways of knowing, as opposed to what I know, is my exploration of context and assumptions. By interacting with my cultural, intellectual, economic, and social history, I seek to become critically aware of the biographical, historical, and cultural context of my beliefs and feelings about myself. This Portfolio is not exclusively for historians of economics or historians of ideas but also for those interested in becoming more aware of how these culturally assimilated frames of reference and bundles of assumptions that influence the way they perceive, think, decide, feel and interpret their experiences in order to operate more effectively in their professional and organisational lives. In the first part of my Portfolio, I outline and reflect upon my Portfolio’s overarching theory of adult development; the writings of Harvard’s Robert Kegan and Columbia University’s Jack Mezirow. The second part delves further into how meaning-making, the activity of how one organises and makes sense of the world and how meaning-making evolves to different levels of complexity. I explore how past experience and our interpretations of history influences our understandings since all perception is inevitably tinged with bias and entrenched ‘theory-laden’ assumptions. In my third part, I explore the 1933 inaugural University College Dublin Finlay Lecture delivered by economist John Maynard Keynes. My findings provide a new perspective and understanding of Keynes’s 1933 lecture by not solely reading or relying upon the text of the three contextualised essay versions of his lecture. The purpose and context of Keynes’s original longer lecture version was quite different to the three shorter essay versions published for the American, British and German audiences.