The perceptions of bullying and the amount of training related to bullying issues experienced by principals was the topic of this study. Elementary principals in the Commonwealth of Virginia were surveyed on their understanding of bullying, the amount of training they received, and what additional staff development needs they perceived would help them to effectively deal with the problem of bullying in their schools. The study found that principals varied in their understanding of the definition of bullying and needed more information and training in order to effectively deal with this problem. The study makes recommendations for how school districts can increase principals' understanding of bullying and what training needs to be implemented to help principals effectively deal with this problem. / Ph. D.

Peer bullying is a widespread and longstanding problem in school settings. Teachers, students, administrators, government, and researchers alike have all tried to combat bullying through bullying prevention campaigns. One strategy used in bullying prevention campaigns is to call on bystanders in bullying situations to take responsible action. While many different forms of campaigns, including print and media campaigns, have aimed at trying to reduce the presence of bullying in schools by informing bystanders, there is still a need to find new strategies for reducing bullying behavior. One potential media form that could be used in bullying prevention campaigns is the use of virtual reality. Virtual reality simulations allow for a more immersive environment than other media forms, as the medium is capable of creating feelings of presence, various perspectives, and empathy in its users. This thesis reports results from a one-factor, three-condition laboratory experiment comparing responses to portrayals of a bullying situation in which users (N = 78) were placed in the perspective of a bystander in a bullying scenario across three different media stimulus conditions: a customized virtual reality condition, a non-customized virtual reality condition, and a video condition. The study compared effects of the media stimulus conditions on empathy, attitudes toward bullying victims and bullying, and anticipated future bystander behaviors, as well as presence and other outcomes related to perceptions of bullying. While it was hypothesized that the study would find stronger effects on empathy and anti-bullying bystander attitudes and anticipated behaviors among the VR conditions, and in particular the customized VR condition, the study found no differences between media stimulus conditions for any outcomes except a significant effect on empathy, with participants in the video condition tending to report more feelings of empathy for participants than participants in the other two conditions, and perceptions of bullying as a problem in the participants' school, again with scores highest in the video condition. This pattern of results was further explored in a follow-up qualitative focus group study (N = 10), in which trends from two focus group sessions featuring 10 participants indicated that the quality of the virtual reality graphics effected empathy, a lack of bystander intervention options reduced effectiveness, and customization cues had little effect on participants. Results from the laboratory experiment and follow-up focus group study suggest that in some cases, it may be difficult to use VR simulations to elicit empathy-related prosocial responses. While further study is needed to clarify what features of VR simulations might make them most effective in encouraging certain prosocial behaviors, findings here suggest that photorealistic graphics should be used in VR simulations to evoke empathy, additional intervention capabilities in VR simulations could make them more effective in producing bystander intervention behavior, and that customization cues should be prominent and possibly individually tailored. ' / Master of Arts

Submitted by PPG Medicina e Ci?ncias da Sa?de (medicina-pg@pucrs.br) on 2018-07-13T12:02:18Z No. of bitstreams: 1 DAVID_PONCIANO_DE_SENA.pdf: 7136289 bytes, checksum: 63e5ded0ad929d80daf354b846f5dd28 (MD5) / Approved for entry into archive by Sheila Dias (sheila.dias@pucrs.br) on 2018-07-18T12:59:17Z (GMT) No. of bitstreams: 1 DAVID_PONCIANO_DE_SENA.pdf: 7136289 bytes, checksum: 63e5ded0ad929d80daf354b846f5dd28 (MD5) / Made available in DSpace on 2018-07-18T13:04:40Z (GMT). No. of bitstreams: 1 DAVID_PONCIANO_DE_SENA.pdf: 7136289 bytes, checksum: 63e5ded0ad929d80daf354b846f5dd28 (MD5) Previous issue date: 2018-04-12 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Aim of the Study: The purpose of this study was to develop and validate a serious game for mobile platforms comparing with a video-assisted self-learning method to assist in the teaching and learning process of cardiopulmonary resuscitation (CPR) maneuvers. In a traditional training, CPR is based on learning by doing using a simulated model with the assistance of an instructor. However, this model presents an overall higher cost and less accessibility, provoking the need for cheaper and more accessible alternative methods. Methods: Forty-five volunteer first-year medical students completed a written multiple choice and practical pretest about CPR maneuvers skills and were randomly allocated into two groups. During a period of 20 minutes, the video self-learning group with 22 students was exposed to a video-based training about CPR, while the video game group with 23 students used a serious game simulating a cardiac arrest scenario where the student should perform virtual CPR to keep playing the game. Each group then performed, a written multiple choice score and practical post-test on a CPR training model while being evaluated by three blinded emergency doctors based on 2015 AHA-BLS (American Heart Association - Basic Life Support) protocol. Both groups were also evaluated about how long they kept interested on each self-learning system. Results: The video group had superior performance as confirmed by a written multiple choice score 7.56+-0.21 against 6.51+-0,21 for a video game (p=0. 001) and practical scores 9.67+-0.21 against 8.40+-0,21 for a video game (p<0. 001). The video game group stayed longer using the method as confirmed by 18.57+- 0,66 minutes for video game group and 7.41+-0,43 for the video group (p<0. 001), demonstrating greater interest in the video game method. Conclusions: The group that used a video game as a self-training method in a short period of exposure had a lower performance than the video group in both the theoretical and practical tests regarding cardiorespiratory resuscitation. However, there was a clear preference for students to use games rather than videos as a form of self-training. / Objetivo do estudo: O objetivo deste estudo foi desenvolver e validar um jogo s?rio para plataformas m?veis em compara??o com um m?todo de autoaprendizagem assistido por v?deo para auxiliar no processo de ensino e aprendizagem das manobras de ressuscita??o cardiopulmonar (RCP). Em um treinamento tradicional, a RCP ? baseada no aprendizado pela pr?tica, utilizando um modelo simulado com a ajuda de um instrutor. No entanto, este modelo apresenta um custo global mais elevado e de menor acessibilidade, despertando a necessidade de m?todos alternativos mais baratos e pratic?veis. M?todos: Quarenta e cinco volunt?rios, estudantes de medicina do primeiro ano, completaram um pr?-teste de m?ltipla escolha escrito e um pr?-teste pr?tico sobre RCP e foram alocados aleatoriamente em dois grupos. Durante um per?odo de 20 minutos, o grupo de autoaprendizagem v?deo, composto por 22 alunos, foi exposto a um v?deo de treinamento sobre a RCP, enquanto o grupo videogame, composto por 23 estudantes, utilizou um jogo s?rio, simulando um cen?rio de parada card?aca, onde o aluno deveria executar uma RCP virtual para continuar jogando. Ao t?rmino do treinamento, cada grupo foi submetido a um p?s-teste escrito de m?ltipla escolha e um p?s-teste pr?tico em um modelo de treinamento de RCP, sendo avaliados de forma cegada, por tr?s m?dicos com experi?ncia em atendimento de emerg?ncia, com base no protocolo 2015 AHA-BLS (American Heart Association - Basic Life Support). Ambos os grupos tamb?m foram avaliados quanto a quantidade de tempo que eles permaneciam interessados em cada sistema de autoaprendizagem. Resultados: O grupo v?deo apresentou desempenho superior confirmado por uma maior pontua??o no teste escrito de m?ltipla escolha, 7.56 + -0.21 contra 6.51 + -0,21 para videogame (p = 0. 001) e pontua??o no teste de avalia??o pr?tica 9,67 + -0,21 contra 8,40 + -0,21 para videogame (p <0. 001). O grupo videogame permaneceu mais tempo utilizando o m?todo, 18,57 + - 0,66 minutos para o grupo videogame e 7,41 + -0,43 para o grupo v?deo (p <0. 001), demonstrando maior interesse no m?todo do videogame. Conclus?es: O grupo que usou o jogo s?rio (grupo videogame) como um m?todo de autotreinamento em um curto per?odo de exposi??o teve um desempenho pior do que o grupo v?deo nos testes te?ricos e pr?ticos em rela??o ? ressuscita??o cardiopulmonar. No entanto, houve uma clara prefer?ncia por parte dos alunos em utilizar jogos em rela??o aos v?deos como forma de autotreinamento.

Bakgrund: Dödligheten vid hjärtstopp utanför sjukhus är hög och endast några få procent av de som drabbas räddas till livet. Tidig behandling är en avgörande faktor för överlevnad. Överlevnaden kan ökas markant av att människor på platsen, bystanders, ingriper med hjärt-lungräddning (HLR). Att vårda och utföra vårdhandlingar är inte exklusivt för sjuksköterskor. Vid hjärtstopp utanför sjukhus är det istället bystandern som förväntas utföra vårdhandlingen. I många fall sker dock inget ingripande trots att hjärtstoppet bevittnas och den vårdande handlingen uteblir därför. Syfte: Syftet med arbetet var att identifiera faktorer som påverkar människors vilja att ingripa vid hjärtstopp utanför sjukhus. Metod: Arbetet designades som en litteraturstudie där artiklar med både kvantitativ och kvalitativ ansats ingick. Resultat: Resultatet baserades på potentiella bystanders antaganden av hur de skulle agera och faktiska bystanders erfarenheter av att ha agerat. Skillnader i faktorer som påverkade viljan observerades mellan dessa. Viljan påverkades till stor del av rädslor, bristande HLR-kunskaper samt scenariot kring hjärtstoppet där bland annat en familjerelation mellan den drabbade och bystandern utgjorde en påverkande faktor. Slutsats: Resultatet visar att hindrande faktorer för viljan skulle kunna påverkas positivt genom förbättrad HLR-utbildning. Klinisk betydelse: Med hjälp av identifierade faktorer kan befintlig HLR-utbildning ses över och eventuellt förbättras. Detta skulle kunna öka antalet ingripanden och därigenom överlevnaden vid hjärtstopp utanför sjukhus. / Background: The lethality is high in out-of-hospital cardiac arrests and only a few percent of the victim’s lives are saved. Early treatment is crucial for survival. People at the scene can increase the survival significantly through CPR interventions. To care and the act of caring is not exclusively for nurses. In cases of out-of-hospital cardiac arrest, the bystander could be the one that performs the act of caring. In many cases, however, no interventions are made although the arrest is witnessed and therefore no act of caring is being performed. Objective: The aim of this essay was to identify factors that influence people's willingness to intervene in out-of-hospital cardiac arrest. Method: This study was designed as a literature study and both quantitative and qualitative research articles were included in the analysis. Results: The result was based on potential bystander's assumptions of how they would act and actual bystanders experience having acted. Differences in factors affecting the willingness were observed between them. The will seemed influenced by fears, lack of CPR skills and the scenario surrounding the arrest. A family tie between the victim and the bystander appeared also as an influencing factor. Conclusion: The findings show that the non-willingness to act could be affected positively by improved CPR training. Clinical significance: In light to the identified factors, improvement of the existing CPR training and increased education could improve the probability of intervention by bystanders and out-of-hospital cardiac arrest survival.

L’efficacité d’une radioimmunothérapie (RIT) peut impliquer la coexistence des effets ciblés et des effets dit « non ciblés ». Les effets ciblés regroupent les effets biologiques observés dans les cellules ou tissus traversés par les particules ionisantes alors que les effets non-ciblés (ou bystander) sont observés dans des cellules qui n’ont pas été irradiées mais qui sont au proche voisinage des cellules exposées. Nous avons au cours de cette étude évalué in vitro et in vivo, la contribution des effets ciblés et non ciblés dans l’efficacité obtenue lors de la RIT alpha (212Pb, 213Bi) et de la RIT Auger (125I). Les effets ciblés ont été mesurés in vitro sur les cellules irradiées (cellules donneuses) alors que les effets bystander sont mesurés sur les cellules non irradiées (cellules receveuses) par une méthode de transfert de milieu. Elle consiste, à traiter les cellules receveuses dans un milieu de culture pré-incubé pendant 2h avec les cellules donneuses. Nos résultats montrent que la contribution des effets ciblés est nettement plus importante qu’en RIT alpha qu’Auger. En RIT alpha, on observe que les lésions de l’ADN (foci 53BP1et γ-H2AX) pourraient être différenciées en lésions complexes (sites multilésés = observation de gros foci) ou simples lésions (petit foci). Par contre en RIT Auger, ce sont les effets non ciblés qui prédominent sur les effets ciblés. L’utilisation d’inhibiteurs pharmacologiques des ROS montre l’implication du stress oxydatif dans ces effets non ciblés observés en RIT alpha et Auger. Ces effets non ciblés ont été observés également in vivo sur des souris athymiques porteuses de carcinoses péritonéales de petites tailles ; démontrant ainsi leur contribution dans l’efficacité thérapeutique finale observée après la RIT alpha et Auger. L’ensemble de ces résultats indiquent que même si des lésions de l’ADN sont produites après irradiation, que les effets non ciblés pourraient aussi contribuer à l’efficacité thérapeutique finale observée avec les anticorps couplés aux émetteurs de particules alpha ou d’électrons Auger. Ces résultats sont particulièrement intéressants pour la thérapie ciblée car les vecteurs utilisés n’ont pas souvent accès à l’ensemble des cellules constituant la tumeur. / We investigated in vitro and in vivo the relative contribution of targeted and non-targeted effects in the therapeutic efficacy against tumors of antibodies radiolabeled with alpha particle (212Pb, 213Bi) or Auger electron (125I) emitters. Targeted effects occurs in cells directly crossed by ionising particles while non-targeted effects are measured in cells neighbouring irradiated cells. Targeted effects were measured in vitro in cells exposed to antibodies radiolabeled with alpha or Auger emitters (donor cells) while non-targeted effects were investigated in recipient cells. Recipient cells consisted of cells not exposed to radiolabeled-mAbs, but grown in medium previously incubated for 2h with donor cells. We showed that the relative contribution of targeted effects versus non-targeted effects was higher during alpha RIT than Auger RIT. Alpha particles produced 53BP1 and gamma-H2AX foci in donor cells that could be differentiated in large, medium and small foci, while only small foci were observed in recipient cells. We assumed that large foci would correspond to locally multiply damage sites in DNA. Conversely, Auger RIT led predominantly to non-targeted effects compared with targeted effects. Use of radical scavengers showed that oxidative stress was involved in non-targeted effects. In vivo, we showed in athymic nude mice bearing tumor xenograft that non-targeted effects were also involved and participated to therapeutic efficacy of radiolabeled antibodies. These results indicate that although producing single DNA lesion, non-targeted effects can contribute to the therapeutic efficacy of mAbs radiolabeled with alpha particle or Auger electron emitters. These findings are particularly relevant for targeted therapy in which vectors cannot gain access to every tumor cell.

The radiation-induced bystander effect is an important phenomenon in the field of radiation biology. It has been shown that cells, after exposure to radiation, can communicate with surrounding cells and affect their physiology. Otherwise-healthy recipient cells can be influenced to undergo cellular senescence or apoptosis through this process. This has potential utilizations for radiation oncology and as well as our understanding of radiation safety. The radiation-induced bystander effect has been extensively investigated since the 1990s, but the scientific community struggles to come to a unanimous decision on how strongly these signals impact the survival of bystander cells. Results show various degrees of impact on cell survival whereas certain studies refute the existence of a radiation-induced bystander effect. This may be due to the fact that there is a great deal of study heterogeneity within the radiation-induced bystander effect community. Most experiments follow a similar general bystander protocol but often use different donor and reporter cell lines that vary in sex, organ of origin, and p53 status. The type of radiation and dose rate also typically differ between experimental designs. In this analysis, 67 in vitro, medium-transfer, radiation-induced, bystander effect studies were retrospectively graphed and analyzed to determine which intrinsic and external factors contributed significantly to the overall survival percentage change observed in reporter cells. A Two-Way ANOVA was conducted on each variable and showed that the reporter cell line, p53 status, and radiation type had a statistically significant effect on survival percentage change. These findings may explain the variation in results seen in past experiments and may help standardize future research allowing for more direct comparisons. / Thesis / Master of Science (MSc)

Des personnes traitées injustement, des biens culturels en danger, la discrimination contre les minorités, l’harcèlement sexuel, l'intimidation et la violence sont seulement quelques comportements incivils et immoraux que nous pouvons témoigner dans les lieux publics. Quelle est notre réaction immédiate ? La présente thèse a examiné les caractéristiques de la personnalité des individus qui expriment leur désaccord et confrontent les auteurs des comportements incivils ou immoraux (Chapitre 1 & Chapitre 2). Nous avons vérifié si ceux qui interviennent ont tendance à être des « râleurs rancuniers » ou des « leaders bien adaptés ». Les deux premières études mesures des nombreuses différences individuelles qui seraient directement impliquées dans la réaction du témoin. Les résultats ont clairement confirmé l'hypothèse du « leader bien adapté ». La tendance des participants à confronter les transgresseurs est en corrélation positive avec la responsabilité sociale, l'acceptation sociale, l'indépendance, la régulation des émotions, la persistance, l'auto-déterminisme, l'âge et le salaire mensuel, mais pas avec l’agressivité. Trois études supplémentaires confirment l'hypothèse du "leader bien ajusté». Altruisme, outrage moral, implication personnelle, libéralisme politique et extraversion sont en relation avec les réactions auto déclarées des gens. Les données ne soutiennent pas l'idée que la haute estime de soi ou le fait d'être agressif serait nécessaire pour faire face à l'auteur d'un comportement incivil/immoral. Nous discutons des implications de ces résultats pour la perpétuation et le changement des normes sociales. Nous avons également examiné l'effet de la distance sociale témoin-transgresseur sur la tendance du témoin à confronter le transgresseur au sujet de son comportement (Chapitre 3). Nous avons présenté 26 comportements incivils et immoraux aux collégiens, lycéens et étudiants à l’université en leur demandant d'indiquer comment ils réagiraient s’ils devaient assister à chacun de ces comportements. Nous avons manipulé la relation avec le transgresseur, qui a été décrit comme soit un ami, soit une connaissance, soit un étranger pour le témoin. Les résultats suggère qu’une relation étroite entre le témoin et l'auteur du comportement incivil/immoral, agrandi la probabilité que le témoin exprime son désaccord. Les résultats parlent du rôle des relations étroites dans la perpétuation des normes sociales. Ils suggèrent également des moyens de réduire les comportements antisociaux dans plusieurs milieux sociaux, scolaires et organisationnels. / People treated unfairly, cultural assets in danger, discrimination against minorities, sexual harassment, bullying and violence are just a few uncivil and immoral behaviors that we can witness in public settings. What is our immediate reaction? The present research examined the personality characteristics of individuals who "speakup" and confront perpetrators of uncivil or immoral behaviors (Chapter 1 & Chapter 2). We tested whether those who intervene tend to be "bitter complainers" or "well-adjusted leaders".The first two studies, measured numerous individual differences that are directly implicated in bystander’s intervention. The results clearly confirmed the well-adjusted leader hypothesis. Participants' self-reported tendency to confront perpetrators correlated positively with social responsibility, acceptance by peers, independent self-construal, emotion regulation, persistence, self-directedness, age, and monthly salary, but not with aggressiveness. Three additional studies provide support for the "well-adjusted leader" hypothesis. Altruism, moral outrage, personal implication, political liberalism, and extraversion were positively related to people's self-reported reactions. The data provided no support for the idea that high self esteemor being aggressive is necessary to confront the perpetrator of an uncivil/immoral behavior. We discuss the implications of these findings for the perpetuation and change of social norms. We also examined the effect of social distance between a bystander and the perpetrator of an uncivil/immoral behavior on the bystander's tendency to "speak up" and confront the perpetrator about his/her behavior (Chapter 3). We presented 26 uncivil and immoral behaviors to middle schoolers, high schoolers and university students and asked them to indicate how they would react if they were to witness each of the behaviors. We manipulated the relationship to the perpetrator who was described as a friend, an acquaintance, or a stranger. Results showed that smaller the social distance between the bystander and the perpetrator of the uncivil/immoral behavior the greater the self-reported likelihood that the bystander will express his/her disapproval to the perpetrator. The findings speak to the role of close relationships in the perpetuation of social norms. They also suggest ways to curb antisocial behaviors in a variety of school and organizational settings.

In der vorliegenden Arbeit wurden die grundlegenden Mechanismen der Glukokortikoidtherapie bei der MS anhand des Tiermodells der MS, der EAE, untersucht. Hierzu wurde die EAE aktiv mithil-fe von MOG35-55 in C57Bl/6-Mäusen sowie GRdim- und lckGRdim-Mäusen induziert.  Zum einen sollte die Wirkung von Dexamethason auf Bystander- und Effektor-T-Zellen gesondert voneinander betrachtet werden. Hierzu sollte zunächst ein Modell etabliert werden, bei dem die GCs nur auf die Bystander- beziehungsweise nur auf die Effektor-T-Zellen wirkten. Trotz zahlrei-cher Experimente konnte kein Modell etabliert werden, dass den Ansprüchen für die Beantwor-tung der Frage genügte.  Zum anderen wurde in dieser Arbeit gezeigt, dass lckGRdim-Mäuse trotz fehlender Dimerisierungs-fähigkeit des GRs und somit fehlender Apoptose-Induktion in T-Zellen auf die GC-Therapie ebenso gut ansprachen wie Kontrolltiere. Ebenso konnte dies bei reinen GRdim-Tieren beobachtet werden. Zunächst wurde mithilfe von Zellzählungen, FACS-Analysen nach Anfärben der Splenozyten mit AxV und einem Apoptose-Assay ausgeschlossen, dass es in den Tieren mit dem veränderten GR doch zu einer Induktion von Apoptose kam. So konnte bestätigt werden, dass Apoptose nicht es-sentiell für die Therapie der EAE ist. Anhand eines Proliferations-Assays konnte ebenso ausgeschlossen werden, dass GCs unspezifisch die gesamte Funktionalität der Zellen beeinflussen. Im Folgenden wurden weitere mögliche Me-chanismen der Wirkung von GCs in der EAE untersucht.  Anhand von FACS-Analysen und qPCR sowie histologischen Untersuchungen konnte gezeigt wer-den, dass die eingeschränkte Migration der Zellen in das RM nach Dex-Gabe eine wichtige Rolle zu spielen scheint. So sahen wir eine Herunterregulierung von Adhäsionsmolekülen sowie die ver-minderte Expression von einigen Zytokinen. Im Falle der Chemokine, die jedoch nur als Neben-schauplatz in dieser Arbeit betrachtet werden, konnte keine Herunterregulierung von RANTES in GRdim-Tieren beobachtet werden. Andere Publikationen geben jedoch Hinweise darauf, dass auch die Beeinflussung der Chemokine entscheidend am Mechanismus der GC-Therapie beteiligt ist.   Zusammenfassend konnte mit dieser Arbeit gezeigt werden, dass Transaktivierungsprozesse, im Speziellen die Induktion von Apoptose, keinen entscheidenden therapeutischen Effekt von Dex darstellen. Der tatsächliche Mechanismus konnte auch im Rahmen dieser Arbeit nicht geklärt wer-den. Durch die Versuche an GRdim-Tieren gibt es jedoch entscheidende Hinweise darauf, dass vor allem repressive Effekte als Wirkungsmechanismus der Kortisontherapie entscheidend sind. Hierzu zählen zum Beispiel die verminderte Expression von Adhäsionsmoleküle sowie die verminderte Ausschüttung von Zytokinen bzw. Sekretion von Chemokinen. Zusammengenommen also Prozes-se, die die Migration von T-Zellen ins ZNS beeinflussen und steuern.  Dieser Aspekt hat eine große Bedeutung für die Therapie der MS, da gerade die Gene, die durch Transaktivierung induziert werden, zu den unerwünschten Nebenwirkungen der Therapie führen. Da diese keine Bedeutung in der Wirksamkeit der GC-Therapie zu haben scheinen, könnten Medi-kamente entwickelt werden, die selektiv die Gene, die durch Transrepression aktiviert werden, ansteuern. Dies würde ein großes Benefit für MS-Patienten nach sich ziehen, die im Rahmen der notwendigen Therapie ihrer Erkrankung mit teilweise gravierenden Nebenwirkungen zu kämpfen haben.

Submitted by LISIERY NEGRINI PAIATTO null (lisy_paiatto@hotmail.com) on 2017-10-23T19:38:26Z No. of bitstreams: 1 DISSERTAÇÃO LISIERY NEGRINI PAIATTO.pdf: 2873819 bytes, checksum: 5b03d17f06d1cc030a85241da7535ae7 (MD5) / Approved for entry into archive by Luiz Galeffi (luizgaleffi@gmail.com) on 2017-10-26T12:04:52Z (GMT) No. of bitstreams: 1 paiatto_ln_me_rcla.pdf: 2873819 bytes, checksum: 5b03d17f06d1cc030a85241da7535ae7 (MD5) / Made available in DSpace on 2017-10-26T12:04:52Z (GMT). No. of bitstreams: 1 paiatto_ln_me_rcla.pdf: 2873819 bytes, checksum: 5b03d17f06d1cc030a85241da7535ae7 (MD5) Previous issue date: 2017-08-31 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A quebra da tolerância imunológica a antígenos próprios é um mecanismo gerador comum às respostas imunes deletérias. Várias estratégias têm sido propostas para modular respostas autoimunes, entre as quais se destacam a administração oral de antígenos relacionados à doença, a transferência adotiva de células tolerogênicas e/ou o tratamento com citocinas reguladoras. Nesse contexto, tem sido mostrado que a ingestão de antígenos proteicos presentes na dieta pode gerar efeitos indiretos sobre o sistema imune do hospedeiro, caracterizados pela supressão da resposta imune a proteínas antigenicamente não relacionadas, conhecidos como supressão bystander. O presente projeto teve por objetivo analisar os efeitos indiretos da tolerância oral induzida pela ingestão de ovalbumina (OVA) e a transferência adotiva de células dendríticas isoladas de animais tolerantes a OVA (tDC) na colite induzida por TNBS em camundongos. Os resultados mostraram que o tratamento de camundongos com OVA por via oral, antes ou após a indução da colite e a transferência adotiva de tDC, foram capazes de reduzir sinais da doença, tais como a perda de peso, bem como preservar parcialmente a integridade do tecido colônico, quando comparados aos animais colíticos não tratados com OVA (controles). A supressão bystander relacionada ao consumo de OVA foi associada à expansão da frequência de células T reguladoras (regs) e de células T secretoras de interleucina (IL) -10, possíveis mecanismos de regulação das manifestações clínicas da colite induzida por TNBS. As DC obtidas de animais tolerantes a OVA apresentaram expressão aumentada de CD80, compatível com perfil tolerogênico. A transferência dessa população de células para animais colíticos foi capaz de reduzir os sinais clínicos e histológicos da colite, mimetizando os efeitos da tolerância oral. A transferência adotiva de tDC levou a redução da frequência de células Th17, redução de secreção de IL-17 e IL-9 e aumento de secreção de IL-10 e IL-4 in vitro. Até onde é de nosso conhecimento, não existem dados na literatura mostrando o efeito da tolerância oral e a transferência adotiva de tDC no tratamento de colite. / The breakdown of immune tolerance to self antigens is a common mechanism for deleterious immune responses. Several interventions have been proposed to modulate autoimmune responses, such as oral administration of disease-related antigens, adoptive transfer of tolerogenic cells and/or treatment with regulatory cytokines. In this context, it has been demonstrated that the ingestion of protein antigens can generate indirect effects on the immune system of the host, characterized by suppression of the immune response to antigenically unrelated proteins, known as bystander suppression. The present project aims to analyze the indirect effects of oral tolerance induced by ovalbumin (OVA) and by adoptive transfer of tolerant dendritic cells (tDC) in TNBS induced colitis in mice. Our results showed that the treatment of oral OVA mice before or after induction of colitis and the adductive transfer of tDC were able to reduce the signs of the disease, such as weight loss, as well as partially preserve the integrity of the Compared to non-OVA treated animals (controls). The bystander suppression related to OVA consumption appears to favor the expansion of regulatory (regs) T and interleukin (IL)-10 secreting T cells responsible for reducing the clinical manifestations of TNBS-induced colitis. On the other hand, DC obtained from OVA-tolerant animals showed increased expression of CD80. Administration of this cells population to colitic animals was able to reduce the clinical and histological signs of colitis, possibly by reducing Th17 cells, reduction of secretion of Il-17 and IL-9 and augment of IL-10 and IL-4. To the best of our knowledge, there are no data in the literature showing the effect of oral tolerance and the adoptive transfer of tDC in the treatment of colitis. / FAPESP: 2013/20258-2

Bystander programs aim to prevent personal violence, such as dating violence, sexual violence, sexual harassment, and stalking. They equip community members with skills to stop the violence before it happens by engaging in active bystander behaviors such as speaking up in potentially risky situations or supporting victims. Given that victimization and perpetration of personal violence, including co-occurrence, are common among youth, high schools have begun implementing bystander programs in recent years. This study examined the relationship between high school students’ experience of personal violence and their active bystander behaviors. Using the social identity approach as a theoretical foundation, this study hypothesized that polyvictims with two types of personal violence victimization would be more active as bystanders compared to those with no or one victimization experience. The study also hypothesized that polyperpetrators with two types of personal violence perpetration would be less active as bystanders compared to those with no or one perpetration experience. The study utilized a secondary dataset from a five-year study, Green Dot across the Bluegrass, which examined the effectiveness of the bystander program Green Dot in reducing rates of personal violence. Using network visualization techniques, commonly co-occurring violence types were identified. Cross-tabulation was used to examine the relationship between experience of co-occurring violence and individual characteristics, including sex, grade, sexual orientation, and exposure to parental partner violence. One-Way Analysis of Variance (ANOVA) was conducted to examine differences in active bystander behaviors based on victimization levels and on perpetration levels. One-Way Analysis of Covariance (ANCOVA) was also used to examine differences in active bystander behaviors based on victimization levels and perpetration levels after controlling for sex, rape myth acceptance, dating violence acceptance, and exposure to the bystander program. Findings revealed that polyvictimization and polyperpetration were both significantly associated with sex, grade, sexual attraction, and exposure to parental partner violence. Polyvictims showed significantly higher levels of active bystander behaviors than those with single or no victimization. Polyperpetrators also showed significantly higher levels of active bystander behaviors than students in other perpetration categories. Future research should include contextual variables such as level of injuries, intent of perpetration, and history of violence in order to more accurately distinguish victimization and perpetration. Suggestions for practice and policies include intervention in adult intimate partner violence to reduce impact on children. It is also recommended that bystander programs to be made relevant to students who are not exclusively heterosexual. Considering the potential presence of victims among participants, the program staff should be aware of impact of trauma and be prepared to provide support as needed. Finally, more rigorous investigation of the impact of bystander programs on youth who are victims as well as perpetrators is warranted.