Comparison of prophylactic and therapeutic use of short-chain fatty acid enemas in diversion colitis: a study in Wistar rats

OBJECTIVES: To study the effect of short-chain fatty-acids on atrophy and inflammation of excluded colonic segments before and after the development of diversion colitis. INTRODUCTION: Diversion colitis is a chronic inflammatory process affecting the dysfunctional colon, possibly evolving with mucous and blood discharge. The most favored hypotheses to explain its development is short-chain fatty-acid deficiency in the colon lumen. METHODS: Wistar rats were submitted to colostomy with distal colon exclusion. Two control groups (A1 and B1) received rectally administered physiological saline, whereas two experimental groups (A2 and B2) received rectally administered short-chain fatty-acids. The A groups were prophylactically treated (5th to 40th days postoperatively), whereas the B groups were therapeutically treated (after post-operative day 40). The mucosal thickness of the excluded colon was measured histologically. The inflammatory reaction of the mucosal lamina propria and the lymphoid tissue response were quantified through established scores. RESULTS: There was a significant thickness recovery of the colonic mucosa in group B2 animals (p = 0.0001), which also exhibited a significant reduction in the number of eosinophilic polymorphonuclear cells in the lamina propria (p = 0.0126) and in the intestinal lumen (p = 0.0256). Group A2 showed no mucosal thickness recovery and significant increases in the numbers of lymphocytes (p = 0.0006) and eosinophilic polymorphonuclear cells in the lamina propria of the mucosa (p = 0.0022). CONCLUSION: Therapeutic use of short-chain fatty-acids significantly reduced eosinophilic polymorphonuclear cell numbers in the intestinal wall and in the colonic lumen; it also reversed the atrophy of the colonic mucosa. Prophylactic use did not impede the development of mucosal atrophy

Searching for Masculine Capital: Experiences Leading to High Drive for Muscularity in Men

Studies on the drive for muscularity (DFM) have primarily been quantitative, focused on identifying correlates. Currently little is known about men’s experiences leading them to desire high levels of muscle and engage in behaviours to increase their masculine capital. Our purpose was to explore the stories of men with high DFM revealing the socio-cultural and personal factors leading to DFM and their search for masculine capital. In-depth life-history interviews and multiple in-the-field conversations were undertaken with twenty men (Mean age=28.45, SD=6.96, years) scoring ≥ 3 on the Drive for Muscularity Scale (Mean=4.30, SD=0.70). Men’s stories focused on a set of dysfunctional childhood and adolescent socio-cultural interactions, including forms of symbolic violence, between them and significant others. In these interactions men were exposed to dominant social narratives of masculinity, and through comparisons and reinforcement they identified discrepancies between themselves and these narratives. In late adolescence and early adulthood men came to believe that they lacked masculine capital. Men struggled to increase their masculine capital through engagement with other traditional masculine activities (e.g., sport) and driven by activating events, they compensated through DFM desires and behaviours. This study advances knowledge by revealing the socio-cultural and personal processes participants believed led to their high DFM. Findings disclose that men’s search for masculine capital may have led them to develop and maintain high levels of DFM.

Postpartum Psychosis in Bipolar Disorder: No Association with Personality, Cognitive Style and Temperament

Background and Aims: Bipolar disorder has been associated with a number of personality traits, cognitive styles and affective temperaments. Women who have bipolar disorder are at increased risk of experiencing postpartum psychosis, however no previous research has investigated these traits in relationship to postpartum episodes. Our aim was to establish whether aspects of personality, cognitive style and affective temperament, that have been associated with bipolar disorder, confer vulnerability to postpartum psychosis over and above their known association with bipolar disorder. Methods: Participants were 552 parous women with DSM-IV bipolar I disorder recruited into the Bipolar Disorder Research Network (www.bdrn.org). Postpartum psychosis group: lifetime episode of postpartum psychosis within 6 weeks of delivery (N = 284). Non-postpartum psychosis group: no history of any perinatal mood episodes (N = 268). Bipolar disorder-associated personality traits (neuroticism, extraversion, schizotypy and impulsivity), cognitive styles (low self-esteem and dysfunctional attitudes) and affective temperaments were measured using well validated self-report questionnaire measures. Results: After controlling for key demographic, clinical and pregnancy-related variables, and measures of current mood state, there were no statistically significant differences between the postpartum psychosis group and non-postpartum psychosis group on any of the personality, cognitive style or affective temperament measures. Conclusions: Personality traits, cognitive styles and affective temperaments associated with the bipolar disorder diathesis in general were not associated with the onset of postpartum psychosis specifically. We have found no evidence that these traits should play a key role when evaluating risk of postpartum psychosis in women with bipolar I disorder considering pregnancy.

Regenerative Cues of Myeloid Cells on Pancreatic Epithelium

Thesis (Ph.D.)--University of Washington, 2016-07

Adult missing persons: can an investigative framework be generated using behavioral themes?

There is a limited amount of research in the area of missing persons, especially adults. The aim of this research is to expand on the understanding of missing people, by examining adults' behaviours while missing and determining if distinct behavioural themes exist. Based on previous literature it was hypothesised that three behavioural themes will be present; dysfunctional, escape, and unintentional. Thirty-six behaviours were coded from 362 missing person police reports and analysed using smallest space analysis (SSA). This produced a spatial representation of the behaviours, showing three distinct behavioural themes. Seventy percent of the adult missing person reports were classified under one dominant theme, 41% were ‘unintentional’, 18% were ‘dysfunctional’, and 11% were ‘escape’. The relationship between a missing person's dominant behavioural theme and their assigned risk level and demographic characteristics were also analysed. A significant association was found between the age, occupational status, whether they had any mental health issues, and the risk level assigned to the missing person; and their dominant behavioural theme. The findings are the first step in the development of a standardised checklist for a missing person investigation. This has implications on how practitioners prioritise missing adults, and interventions to prevent individuals from going missing. Copyright © 2016 John Wiley & Sons, Ltd.

Identification and characterisation of telomere regulatory and signalling pathways after induction of telomere dysfunction

Telomeres are DNA-protein complexes which cap the ends of eukaryotic linear chromosomes. In normal somatic cells telomeres shorten and become dysfunctional during ageing due to the DNA end replication problem. This leads to activation of signalling pathways that lead to cellular senescence and apoptosis. However, cancer cells typically bypass this barrier to immortalisation in order to proliferate indefinitely. Therefore enhancing our understanding of telomere dysfunction and pathways involved in regulation of the process is essential. However, the pathways involved are highly complex and involve interaction between a wide range of biological processes. Therefore understanding how telomerase dysfunction is regulated is a challenging task and requires a systems biology approach. In this study I have developed a novel methodology for visualisation and analysis of gene lists focusing on the network level rather than individual or small lists of genes. Application of this methodology to an expression data set and a gene methylation data set allowed me to enhance my understanding of the biology underlying a senescence inducing drug and the process of immortalisation respectively. I then used the methodology to compare the effect of genetic background on induction of telomere uncapping. Telomere uncapping was induced in HCT116 WT, p21-/- and p53-/- cells using a viral vector expressing a mutant variant of hTR, the telomerase RNA template. p21-/- cells showed enhanced sensitivity to telomere uncapping. Analysis of a candidate pathway, Mismatch Repair, revealed a role for the process in response to telomere uncapping and that induction of the pathway was p21 dependent. The methodology was then applied to analysis of the telomerase inhibitor GRN163L and synergistic effects of hypoglycaemia with this drug. HCT116 cells were resistant to GRN163L treatment. However, under hypoglycaemic conditions the dose required for ablation of telomerase activity was reduced significantly and telomere shortening was enhanced. Overall this new methodology has allowed our group and collaborators to identify new biology and improve our understanding of processes regulating telomere dysfunction.

Comparison of prophylactic and therapeutic use of short-chain fatty acid enemas in diversion colitis: a study in Wistar rats

OBJECTIVES: To study the effect of short-chain fatty-acids on atrophy and inflammation of excluded colonic segments before and after the development of diversion colitis. INTRODUCTION: Diversion colitis is a chronic inflammatory process affecting the dysfunctional colon, possibly evolving with mucous and blood discharge. The most favored hypotheses to explain its development is short-chain fatty-acid deficiency in the colon lumen. METHODS: Wistar rats were submitted to colostomy with distal colon exclusion. Two control groups (A1 and B1) received rectally administered physiological saline, whereas two experimental groups (A2 and B2) received rectally administered short-chain fatty-acids. The A groups were prophylactically treated (5th to 40th days postoperatively), whereas the B groups were therapeutically treated (after post-operative day 40). The mucosal thickness of the excluded colon was measured histologically. The inflammatory reaction of the mucosal lamina propria and the lymphoid tissue response were quantified through established scores. RESULTS: There was a significant thickness recovery of the colonic mucosa in group B2 animals (p = 0.0001), which also exhibited a significant reduction in the number of eosinophilic polymorphonuclear cells in the lamina propria (p = 0.0126) and in the intestinal lumen (p = 0.0256). Group A2 showed no mucosal thickness recovery and significant increases in the numbers of lymphocytes (p = 0.0006) and eosinophilic polymorphonuclear cells in the lamina propria of the mucosa (p = 0.0022). CONCLUSION: Therapeutic use of short-chain fatty-acids significantly reduced eosinophilic polymorphonuclear cell numbers in the intestinal wall and in the colonic lumen; it also reversed the atrophy of the colonic mucosa. Prophylactic use did not impede the development of mucosal atrophy

A importância da prática na construção da profissionalização

Relatório de estágio apresentado à Escola Superior de Educação de Paula Frassinetti para obtenção de grau de Mestre em Ensino do 1º e do 2º Ciclo do Ensino Básico

Nouveaux indices de suppression de la lipolyse par l'insuline déterminés lors de l'hyperglycémie provoquée par voie orale : comparaisons avec le clamp euglycémique-hyperinsulinémique et les paramètres métaboliques chez les femmes

Résumé : Une dysrégulation de la lipolyse des tissus adipeux peut conduire à une surexposition des tissus non-adipeux aux acides gras non-estérifiés (AGNE), qui peut mener à un certain degré de lipotoxicité dans ces tissus. La lipotoxicité constitue, par ailleurs, l’une des causes majeures du développement de la résistance à l’insuline et du diabète de type 2. En plus de ses fonctions glucorégulatrices, l’insuline a pour fonction d’inhiber la lipolyse et donc de diminuer les niveaux d’AGNE en circulation, prévenant ainsi la lipotoxicité. Il n’y a pas d’étalon d’or pour mesurer la sensibilité de la lipolyse à l’insuline. Le clamp euglycémique hyperinsulinémique constitue la méthode étalon d’or pour évaluer la sensibilité du glucose à l’insuline mais il est aussi utilisé pour mesurer la suppression de la lipolyse par l’insuline. Par contre, cette méthode est couteuse et laborieuse, et ne peut pas s’appliquer à de grandes populations. Il existe aussi des indices pour estimer la fonction antilipolytique de l’insuline dérivés de l’hyperglycémie provoquée par voie orale (HGPO), un test moins dispendieux et plus simple à effectuer à grande échelle. Cette étude vise donc à : 1) Étudier la relation entre les indices de suppressibilité des AGNE par l’insuline dérivés du clamp et ceux dérivés de l’HGPO; et 2) Déterminer laquelle de ces mesures corrèle le mieux avec les facteurs connus comme étant reliés à la dysfonction adipeuse : paramètres anthropométriques et indices de dysfonction métabolique. Les résultats montrent que dans le groupe de sujets étudiés (n=29 femmes, 15 témoins saines et 14 femmes avec résistance à l’insuline car atteintes du syndrome des ovaires polykystiques), certains indices de sensibilité à l’insuline pour la lipolyse dérivés de l’HGPO corrèlent bien avec ceux dérivés du clamp euglycémique hyperinsulinémique. Parmi ces indices, celui qui corrèle le mieux avec les indices du clamp et les paramètres anthropométriques et de dysfonction adipeuse est le T50[indice inférieur AGNE] (temps nécessaire pour diminuer de 50% le taux de base – à jeun – des AGNE). Nos résultats suggèrent donc que l’HGPO, facile à réaliser, peut être utilisée pour évaluer la sensibilité de la lipolyse à l’insuline. Nous pensons que la lipo-résistance à l’insuline peut être facilement quantifiée en clinique humaine.

Otimização de uma linha de aglomeração de materiais reciclados

Dado a globalização dos negócios e o aumento da competitividade dos produtos, é cada vez mais difícil para as grandes empresas manter a sua posição no mercado. Este processo quer-se rápido, eficaz e com o menor custo possível. Para este efeito, a metodologia Lean tem oferecido respostas bastante interessantes às empresas, com a aplicação de ferramentas da metodologia muito simples mas muito eficientes. Garantir características no produto final que façam á empresa manter ou ganhar cota no mercado é fundamental. Como tal, as empresas tentam ao máximo garantir a qualidade e o aspecto visual do produto. Posto isto, foram efetuados vários trabalhos para fazer frente às situações acima apresentadas e fazer com que o produto continue competitivo, para que possa aumentar a sua margem de lucro, mantendo o seu valor no mercado. Os trabalhos efetuados foram: plano de manutenção autónoma, um estudo do efeito da velocidade do misturador no produto final e um balanceamento à linha de aglomeração. Com a aplicação do Plano de Manutenção Autónoma, foi possível eliminar desperdícios, tornar a linha mais organizada e limpa e instruir os operadores a serem mais responsáveis, organizados e críticos ao seu trabalho. Quanto ao estudo do efeito da velocidade do misturador no produto final, os resultados não foram os esperados, dado que com o ensaio industrial efetuado não foi possível melhorar significativamente o aspeto visual do produto. Apesar de não ter sido possível a sua implementação, com o estudo do Balanceamento da linha, junto com os dados recolhidos foi possível obter um conhecimento mais pormenorizado da linha, foi criada uma possibilidade de proteger a linha de possíveis flutuações do mercado e eliminação de desperdício e uma possibilidade de listagem de tarefas estandartizadas e equilibradas, promovendo um menor esforço aos operadores. Em síntese, com a elaboração destes trabalhos, foi possível provocar um impacto positivo na linha, tornando-a mais organizada, reduzindo desperdício, protegendo de flutuações do mercado e aumentando o conhecimento da mesma.

À procura do esquecimento: A mulher toxicodependente

Dissertação de Mestrado apresentada ao Instituto Superior de Psicologia Aplicada para obtenção de grau de Mestre na especialidade de Psicologia Clínica.

Influence of frequent nightmares on REM sleep-dependent emotional memory processing

La littérature suggère que le sommeil paradoxal joue un rôle dans l'intégration associative de la mémoire émotionnelle. De plus, les rêves en sommeil paradoxal, en particulier leur nature bizarre et émotionnelle, semblent refléter cette fonction associative et émotionnelle du sommeil paradoxal. La conséquence des cauchemars fréquents sur ce processus est inconnue, bien que le réveil provoqué par un cauchemar semble interférer avec les fonctions du sommeil paradoxal. Le premier objectif de cette thèse était de reproduire conceptuellement des recherches antérieures démontrant que le sommeil paradoxal permet un accès hyper-associatif à la mémoire. L'utilisation d'une sieste diurne nous a permis d'évaluer les effets du sommeil paradoxal, comparativement au sommeil lent et à l’éveil, sur la performance des participants à une tâche sémantique mesurant « associational breadth » (AB). Les résultats ont montré que seuls les sujets réveillés en sommeil paradoxal ont répondu avec des associations atypiques, ce qui suggère que le sommeil paradoxal est spécifique dans sa capacité à intégrer les traces de la mémoire émotionnelle (article 1). En outre, les rapports de rêve en sommeil paradoxal étaient plus bizarres que ceux en sommeil lent, et plus intenses émotionnellement ; ces attributs semblent refléter la nature associative et émotionnelle du sommeil paradoxal (article 2). Le deuxième objectif de la thèse était de préciser si et comment le traitement de la mémoire émotionnelle en sommeil paradoxal est altéré dans le Trouble de cauchemars fréquents (NM). En utilisant le même protocole, nos résultats ont montré que les participants NM avaient des résultats plus élevés avant une sieste, ce qui correspond aux observations antérieures voulant que les personnes souffrant de cauchemars soient plus créatives. Après le sommeil paradoxal, les deux groupes, NM et CTL, ont montré des changements similaires dans leur accès associatif, avec des résultats AB-négatif plus bas et AB-positif plus grands. Une semaine plus tard, seul les participants NM a maintenu ce changement dans leur réseau sémantique (article 3). Ces résultats suggèrent qu’au fil du temps, les cauchemars peuvent interférer avec l'intégration de la mémoire émotionnelle pendant le sommeil paradoxal. En ce qui concerne l'imagerie, les participants NM avaient plus de bizarrerie et plus d’émotion positive, mais pas négative, dans leurs rêveries (article 4). Ces attributs intensifiés suggèrent à nouveau que les participants NM sont plus imaginatifs et créatifs à l’éveil. Dans l'ensemble, les résultats confirment le rôle du sommeil paradoxal dans l'intégration associative de la mémoire émotionnelle. Cependant, nos résultats concernant le Trouble de cauchemars ne sont pas entièrement en accord avec les théories suggérant que les cauchemars sont dysfonctionnels. Le groupe NM a montré plus d’associativité émotionnelle, de même que plus d'imagerie positive et bizarre à l’éveil. Nous proposons donc une nouvelle théorie de sensibilité environnementale associée au Trouble de cauchemar, suggérant qu'une sensibilité accrue à une gamme de contextes environnementaux sous-tendrait les symptômes uniques et la richesse imaginative observés chez les personnes souffrant de cauchemars fréquents. Bien que davantage de recherches doivent être faites, il est possible que ces personnes puissent bénéficier e milieux favorables, et qu’elles puissent avoir un avantage adaptatif à l'égard de l'expression créative, ce qui est particulièrement pertinent lorsque l'on considère leur pronostic et les différents types de traitements.

A ansiedade infantil : vulnerabilidades da criança e influência dos pais

Tese de Doutoramento em Psicologia na área de especialidade Psicologia Clínica

Head repositioning accuracy in patients with neck pain and asymptomatic subjects: concurrent validity, influence of motion speed, motion direction and target distance

Background: Cervicocephalic kinesthetic deficiencies have been demonstrated in patients with chronic neck pain (NP). On the other hand, authors emphasized the use of different motion speeds for assessing functional impairment of the cervical spine. Purpose: The objectives of this study were (1) to investigate the head repositioning accuracy in NP patients and control subjects and (2) to assess the influence of target distance, motion speed, motion direction and pain. Materials and methods: Seventy-one subjects (36 healthy subjects and 35 NP patients; age 30–55 years) performed the head repositioning test (HRT) at two different speeds for horizontal and vertical movements and at two different distances. For each condition, six consecutive trials were sampled. Results: The study showed the validity and reproducibility of the HRT, confirming a dysfunctional threshold of 4.5°. Normative values of head repositioning error up to 3.6° and 7.1° were identified for healthy and NP subjects, respectively. A distance of 180 cm from the target and a natural motion speed increased HRT accuracy. Repositioning after extension movement showed a significantly larger error in both groups. Intensity, duration of pain as well as pain level did not significantly alter head repositioning error. Conclusions: The assessment of proprioceptive performance in healthy and NP subjects allowed the validation of the HRT. The HRT is a simple, not expensive and fast test, easily implementable in daily practice to assess and monitor treatment and evolution of proprioceptive cervical deficits.

Identification of telomere dysfunction in Friedreich ataxia.

Background: Friedreich ataxia (FRDA) is a progressive inherited neurodegenerative disorder caused by mutation of the FXN gene, resulting in decreased frataxin expression, mitochondrial dysfunction and oxidative stress. A recent study has identified shorter telomeres in FRDA patient leukocytes as a possible disease biomarker. Results: Here we aimed to investigate both telomere structure and function in FRDA cells. Our results confirmed telomere shortening in FRDA patient leukocytes and identified similar telomere shortening in FRDA patient autopsy cerebellar tissues. However, FRDA fibroblasts showed significantly longer telomeres at early passage, occurring in the absence of telomerase activity, but with activation of an alternative lengthening of telomeres (ALT)-like mechanism. These cells also showed accelerated telomere shortening as population doubling increases. Furthermore, telomere dysfunction-induced foci (TIF) analysis revealed that FRDA fibroblasts have dysfunctional telomeres. Conclusions: Our finding of dysfunctional telomeres in FRDA cells provides further insight into FRDA molecular disease mechanisms, which may have implications for future FRDA therapy.