Emotional responses, whether approach or withdrawal motivated, are fundamental factors in all food-related experiences. In this research project four experiments were completed with the goal of contributing to the growing body of research related to food and emotions. Implicit (unstated) measures of attention, emotional expression, and motivational behavior tendencies were assessed as additional supportive information for explicit (cognitive) measures of acceptability and emotional response to food and attributes of food with quality and safety concerns. Differences in explicit responses were evaluated using a 9-point hedonic scale, check-all-that-apply (CATA) emotion term questionnaire, and a six basic emotion intensity ratings scale. Implicit responses of emotion, attention and motivational behaviors were measured using automated facial expression analysis (AFEA), eye-tracking technology, electrocardiography (ECG) and electroencephalography (EEG). An initial study on light-induced milk oxidation flavor quality indicated reliable explicit measures of emotion and consumer acceptability, while AFEA showed a wide range of facial expression. In a following study, five different control breakfast meal videos were created; three were matched with a nearly identical video that contained one of three food concerns, food spoilage quality, hygiene quality and safety. Explicit measures provided solid support for the expected explicit response differences between food concerning and control breakfast meal types. Implicit measures of heart rate, facial motor expressions and frontal cortex asymmetries (brain activity) were only minimally informative across each measure or conclusive across meal types. The use of time series statistical analyses illustrated temporal changes in emotions when compared to a control condition, which was not evident using traditional analysis of variance approaches. A visual attention study investigated use of eye tracking as an indicator of the emotional responses elicited. Eye tracking technologies, as well as the other implicit measures (ECG, EEG, and AFEA), encountered similar limitations pertaining to participant variability due to personal preferences and characteristics, as well as a need for standard methodologies with food as stimuli and appropriate control conditions. With further research in this area of study, implicit measures of emotion, attention and motivational behaviors may provide additional valuable information to more traditional explicit affective methodologies for a greater understanding of the overall consumer food experience. / Ph. D.

The innate immune system is a critical first line of defense against invading pathogens. Innate immunity directly detects pathogens, sets up an appropriate adaptive response, and can directly kill pathogens. Drosophila may lack an adaptive immune response, but have a robust innate immune system with a variety of defense effector mechanisms. While the responses to bacteria, fungi, and RNA viruses have been well characterized, not much is known about the response to DNA viruses. My studies have set out to characterize the Drosophila immune response to a DNA virus, utilizing the large dsDNA virus, Invertebrate Iridescent Virus 6 (IIV-6). IIV-6 infection causes shortened lifespan, and in later stages of infection, flies present with abdominal swelling and iridescent blue color. Our objectives were to identify pathways flies use to protect themselves from IIV-6 infection, determine how this protection is mediated, and to identify any immune inhibitors that IIV-6 uses to suppress innate immune signaling. I have found that IIV-6 strongly up-regulates a class of stress proteins with unknown function, termed Turandots, after infection in vivo or in vitro. This induction is dependent upon viral replication, requires JAK-STAT activation, and activation of p38b MAPK. In addition, the unpaireds, which function as JAK-STAT ligands, are upregulated after IIV-6 infection in a p38b-dependent manner. Together, this data suggests that p38b activation leads to production of unpaired cytokines and activation of JAK-STAT signaling to induce Turandots. I have also found that IIV-6 infected cells secrete protective factors. This response is induced within 12 hours of IIV-6 infection, exosome-mediated, and provides robust protection to naive cells challenged with an mCherry-expressing strain of IIV-6. Additionally, IIV-6 inhibits two major immune responses in Drosophila, the IMD and Toll pathways. Stimulation of IIV-6 infected Drosophila S2* cells with either IMD or Toll stimulators results in very poor antimicrobial peptide responses. Yet, IMD and Relish are still cleaved upon stimulation in IIV-6 infected cells, indicating that the block is downstream. In support of this finding, IIV-6 infected flies respond very poorly to infection with the enterobacteria Erwinia carotovora carotovora compared to mock-injected flies.

I yrket som terapeut är ämnet suicid ständigt närvarande. När professionella terapeuter hamnar i kris blir reaktionen lika stark som hos andra människor. Vår utgångspunkt var att patientsuicid är en händelse som inte hanteras optimalt i arbetsorganisationen, vilket leder till psykiska, fysiska och sociala konsekvenser för terapeuten, både på arbetsplatsen och i privatlivet. Syftet med studien är att öka kunskapen inom psykoterapiområdet om vad som händer vid ett patientsuicid, bli medveten som terapeut, enskild individ och organisation hur ett patientsuicid påverkar ur ett systemiskt perspektiv. Organisationens förbättrade förmåga att hantera ett patientsuicid bör kunna få positiv betydelse för terapeuten då kunskapen ökar om hur terapeut och system samverkar. Studien grundar sig på sex terapeuters upplevelser av patientsuicid. I resultatet framkommer vad dessa terapeuter upplevt, samt deras synpunkter på vad som skulle kunna förbättras vid framtida patientsuicid. Ett fynd vi gjort är att det bör finnas en flexibilitet i organisationen för individuella bedömningar vad gäller behov av stöd till drabbade terapeuter. Sättet på vilket terapeuter meddelas om patientsuicid, samt av vem, får olika effekter på terapeuten. Organisationen kan utvecklas vad gäller bemötandet av den terapeut som drabbas av patientsuicid. Ytterligare ett viktigt fynd och förbättringsområde är rutiner kring hantering av kontakt med anhöriga.

My research explores the complex strategies animals adapt to cope with multiple selection pressures. I studied the behavioral and color response of two salamander sister species, Ambystoma barbouri and A. texanum, to temperature, predation risk and ultraviolet radiation (UVR, 280-320 nm). Ambystoma barbouri undergo development in streams, while A. texanum larvae inhabit ponds. Thus, A. barbouri are exposed to increased habitat ephemerality, enhanced predation risk, and UVR exposure. I show how A. barbouri have evolved alternate coping mechanisms in response to these environmental factors, relative to A. texanum. In this comparison study, I've quantified the affects of these selection pressures on larval color change, refuge use and depth choice.I found Ambystoma barbouri to have a significantly darker mean color than A. texanum. Additionally, both species significantly change color to match their background and in response to temperature. When exposed to warm temperatures, early-stage larvae of both species became lighter. Both species also changed color over ontogeny, with larvae becoming significantly lighter over development. Remarkably, A. texanum larvae mediated risk from predatory fish chemical cues by visually assessing the degree to which they cryptically match their background. If cryptic, A. texanum larvae remained on that background color rather than in refuge. A. barbouri larvae preferred to hide in refuge or on dark backgrounds regardless of crypticity, butquickly change color to match their new background. I found that both species darken in response to UVR. When given the choice of refuge, both species spent significantly more time in hiding when UVR was present. When given a choice of water depth, larvae preferred deep water in the presence of UVR radiation.Adapting multiple color and behavioral responses to individual selection pressures help organisms mediate conflicting demands from multiple selection pressures. For example, when predatory fish are present, larvae should move to shallow water to avoid predation. In the presence of UVR, however, larvae should prefer deeper water. I found A. barbouri larvae choose deep water to avoid high UVR exposure despite the risk of predation. Evolving multiple behavioral strategies allows A. barbouri larvae to avoid UVR damage and mediate predation risk.

Summary of the work Abdominal aortic aneurysm (AAA) is a chronic degenerative disease that usually affects men over 65 years with an estimated prevalence of 5%. Aneurysm rupture represents a catastrophic event which carries a mortality rate of almost 90%. Current therapeutic options for AAAs measuring 5.5 cm in diameter or larger are based on prophylactic surgery, including conventional open reconstruction and endovascular stent-graft insertion. For patients with small asymptomatic AAAs (4.0 up to 5.5 cm in diameter), evidence from two recent large randomized controlled trials indicates no long-term survival benefit from immediate elective surgical repair as compared to imaging surveillance until aneurysm expands to 5.5 cm. This highlights the need for development of novel medical management strategies, including selective pharmacologic approaches, directed at preventing aneurysm expansion. In this regard, it is expected that a detailed knowledge of the pathobiology of human AAA lesion and a better understanding of pathophysiological mechanisms underlying initiation and progression of aneurysmal degeneration, particularly the specific involvement of T lymphocytes, will have special relevance to this challenging issue. Inflammatory and helper T-cell responses in abdominal aortic aneurysm : controversial issues Innate and inflammatory responses to endovascular versus open AAA repair. The occurrence of early acute systemic inflammatory responses after conventional open AAA repair is widely recognized and is thought to lead to the development of organ dysfunction and multiple organ failure, responsible for a large proportion of morbidity and mortality associated with aortic surgery. New therapeutic strategies designed to avoid ischemia-reperfusion injury related to aortic cross-clamping and to minimize the degree of tissue damage have thus been developed recently. Specifically, the advent of endovascular techniques has radically extended management options for patients with AAA. Although the method is believed to offer a clear short-term benefit over open repair, notably as regards restricted perioperative haemodynamic parameter fluctuations, reduced blood loss, briefer duration of surgery, shorter hospital stay, and lower 30-day mortality and complication rates, conflicting data are available regarding the exact nature and extent of the inflammatory events arising after such endoluminal procedures ; while several authors have indeed reported that endovascular AAA repair can determine a less intense and extensive inflammatory response, others have unexpectedly observed that the method may elicit a strong inflammatory response, the so-called « postimplantation syndrome ». Adaptive cellular immune responses in human aneurysmal aortic lesion. The inflammatory nature of AAA disease has long been suggested by the presence of a great number of CD4+ T lymphocytes in the outer media and adventitia of human AAA lesion. Interestingly, such infiltrating T-cell populations may have significant implications in the process of aneurysm dilation, since cytokines produced by T cells, notably IFN-gamma, have previously been shown to modulate production of matrix-degrading enzymes by resident macrophages and to induce apoptosis of medial SMCs. Through these key pathological mechanisms, T cells could potentially contribute to orchestrate aortic wall connective tissue disordered remodeling and degradation, and promote extensive disruption of elastic media, ultimately leading to aneurysmal degeneration. Nevertheless, despite their relative abundance in human AAA wall tissues, there is limited and controversial information as regards the functional profile of lesional lymphocytes, the exact nature of aortic wall adaptive cellular responses, and the etiologic role of T cells and their cytokines in initiation and progression of the aneurysmal process. Indeed, both Th1-type and Th2-type responses have been identified in human studies and experimental animal models of AAA. Aims of the work The main objectives of our work were to explore the innate and adaptive cellular immune responses in human AAA. In the first part of our work, we aimed to examine prospectively innate and inflammatory responses arising in a non-randomised cohort of patients undergoing endovascular versus open AAA repair. In the second part of our work, we focused our efforts on characterizing the nature of adaptive cellular immune responses and the phenotypic and functional repertoire of T cells in human AAA wall tissues obtained from a consecutive series of patients undergoing open AAA repair. Specifically, we sought to determine whether type 1 or type 2 responses occur predominantly in advanced AAA lesion. Main experimental findings Limited inflammatory response after endovascular AAA repair. Serial peripheral venous blood samples were collected preoperatively, immediately after declamping or insertion of endograft, and after 1, 3, 6, 12, 24, 48, and 72 hours. We first examined the acute phase reaction and liberation of complement cascade products using turbidimetric method and nephelometry. We found that endovascular repair produced lower postoperative CRP, leucocytosis, neutrophilia, and C3d/C3 ratio as compared to open surgery. We next analyzed surface expression of activation markers on peripheral CD3+ T cells using flow cytometry. We observed a strong upregulation of CD38 after open but not endovascular repair. Analysis of CD69 and CD25 molecules revealed no perioperative fluctuations in any group. We then investigated release of various circulating soluble cell adhesion molecules, proinflammatory cytokines, and chemokines using enzyme-linked immunosorbent assays. We demonstrated that both procedures are characterized by similar increases in ICAM-1 and IL-6 levels. Finally, tendency towards high levels of TNF-alpha and IL-8 was detected in endovascular repair, but data failed to reach statistical significance. Predominance of type 1 CD4+ T cells in human aneurysmal aortic lesion. We have developed a tissue enzymatic digestion and cell extraction procedure to isolate intact mononuclear cells from aortic wall segments. This original cell isolation protocol enabled us to examine ex vivo the presence, phenotype, and cytokine secretion profile of infiltrating T lymphocytes freshly isolated from human AAA tissues for comparison with their circulating counterparts using flow cytometry. We found that both populations of infiltrating CD4+ and CD8+ T cells display a unique activated memory phenotype, as assessed by an increased expression of CD69 and HLA-DR activation antigens, downregulation of CD62L molecule, and predominant expression of the CD45RO isoform characteristics of memory cells. In addition, we identified the presence in human aneurysmal aortic wall lesion of CD4+ T cells producing high levels of IFN-gamma but not IL-4, reflecting their type 1 nature. In an additional series of experiments, cytokine gene expression was determined in whole aneurysmal and non-diseased aortic samples using LightCycler-based quantitative real-time reverse transcription-polymerase chain reaction. The molecular basis of type 1 or type 2 dominant responses was further specified by analyzing mRNA levels of transcription factors specifically involved in Th1 or Th2 differentiation such as T-bet and GATA-3. We demonstrated that aneurysmal aortic specimens exhibit high transcript levels of IFN-gamma but not IL-4, and consistently overexpressed the IFN-g-promoting cytokine IL-12 and the type 1-restricted transcription factor T-bet, further establishing the prominent type 1 nature of aortic wall responses. Moreover, such selective tissue expression of IL-12 and T-bet in the vessel microenvironment points to a potential role for these signals in directing aortic wall responses towards a type 1 phenotype. Conclusions Our findings indicate that endovascular AAA repair is associated with a lesser degree of acute phase reaction, peripheral T-cell activation, and release of complement proteins as compared to conventional open surgery, suggesting that the innate and inflammatory responses to AAA repair are significantly attenuated by the endovascular approach as compared to the traditional open reconstruction. These results support the view that the endoluminal procedure represents an attractive alternative to open surgery for the treatment of large aneurysms. On the other hand, we have demonstrated that Th1 cell infiltrates predominate in human end-stage AAA lesion. These observations are relevant for helping clarify the pathobiology of human AAA tissues and defining prospects for the prevention of aneurysm expansion. Indeed, identification of such infiltrating populations of IFN-gamma-producing CD4+ T cells not only provide new insights into the pathogenesis of the disorder, but could also serve as a basis for the development of novel medical management strategies directed at preventing aneurysm formation and progression, including therapeutic approaches based on the modulation of aortic wall responses and designed to selectively target T-cell activation and cytokine production. In this respect, the present work provides experimental evidence in support of the emerging concept that, although multifactorial, aneurysm disease may be regarded as a Th1-driven immunopathological condition, and suggests that strategies targeting IFN-gamma could be a particularly exciting and fruitful avenue for further investigation. Ongoing clinical and basic research in these areas can be expected to yield design of promising pharmacologic approaches to control AAA expansion. From a clinical perspective, such efforts have the potential to dramatically influence both the outcome and management of this common and life threatening condition.

No description available.

Chronic pain is recognized for its intra- and interpersonal stress, with greater social support being associated with better patient outcomes. Urologic Chronic Pelvic Pain Syndromes (UCPPS) are pain-associated conditions that are prevalent across genders and are strongly associated with diminished quality of life (QOL). To date, no gender-based research has examined such supportive behaviours in UCPPS samples. One model, the stress-buffering model of social support, suggests people with greater support within their proximal (e.g., marriage) and distal (e.g., physician) social environment may be protected from negative stressor impact (i.e., pain). Due to their strong associations with poorer QoL, I hypothesized catastrophizing and perceived pain control as important intrapersonal cognitive variables to also consider in such relations between pain and patient QoL. In this dissertation, I examined several research questions using two self-report studies: 1) Are there gender differences in social support for people with UCPPS?; 2) Does social support moderate the relationship between pain and patient outcome variables and are there gender differences in this effect?; and 3) If social support moderates the relationship between pain and outcomes, is this effect further moderated by cognitive variables and/or gender? In Studies 1 and 2, women with IC/PBS endorsed higher levels of solicitous and distracting spouse responses to pain behaviour than did men with CP/CPPS. Additionally, in Study 2 women reported greater support from friends than did men. In regard to moderation effects in Study 1, distracting spouse responses buffered the relationships between patient pain and mental QoL, and between pain and disability. However, spouse solicitousness had a detrimental effect on the relationship between patient pain and mental QoL but only at low levels of catastrophizing in the patient. The genders did not differ in the effect of spouse responses to pain behaviour in Study 1, and Study 1 results with respect to the stress-buffering role of distracting spouse responses were not replicated in Study 2. In Study 2, sources of social support from outside of the marriage also did not have a stress-buffering effect on the relationship between pain and patient outcome. Of the models reviewed, no one current model for understanding the role of social support or catastrophizing in chronic pain was sufficient to account for the findings reported in these studies. However, a dyadic emotion regulation perspective is suggested with implications for marital therapy with couples with chronic pain. / Thesis (Ph.D, Psychology) -- Queen's University, 2013-11-18 19:17:11.276

Cyberbullying is a category of bullying that occurs in the digital realm which affects our students at astonishing rates. Unlike traditional bullying, where displays of aggression may be evident to bystanders, the ramification of cyberbullying occurs through unconventional ways (e.g., text messaging; online weblogs; video sharing), which results in many cases being camouflaged by the advancement in technology. Nonetheless, the effects of this digital form of peer aggression can be as detrimental as face-to-face bullying. The characteristics of cyberbullying and its influences on adolescents and parents of adolescents were examined. The data accrued is based on an anonymous survey through one of the following methods: (a) paper-pencil survey for adolescent group with 37-question items on the adolescent questionnaire and (b) web-based survey for the parent group with 22-question items on the parent questionnaire. Each survey was systematically coded according to the participating group and assigned code numbers (i.e., 1 represents adolescent group and 2 represents parent group) was provided to ensure confidentiality of the study. Survey examined individual variables among the two target groups: (a) adolescents between 13 and 17 years of age and (b) parents of adolescents between 13 and 17 years of age. Specifically, individual variables examined include (a) demographics, (b) personal experiences, (c) vicarious experiences, and (d) preventative resources. A total of 137 participants (62 adolescents; 75 parents) responded to the survey. Results indicated that 90% of the participants from the adolescent group have reported to experience either as victims or as bystanders of cyberbullying. In addition, 70% of the victims have been cyberbullied 1 to 2 times within a month period and 50% of the victims did not know the perpetrator. Secondly, 89% of parent participants indicated to be knowledgeable about the issues relating to cyberbullying and 89% reported to have no knowledge if their child has or has not been a victim of cyberbullying. Furthermore, qualitative findings of personal perspectives toward cyberbullying from each participating group are discussed. A review of literature is provided and results and analysis of the survey are discussed as well as recommendations for future research.

Nonalcoholic steatohepatitis (NASH) has been identified as a source of significant inter individual variation in drug metabolism. A previous ex vivo study demonstrated significant changes in hepatic Cytochrome P450 (CYP) activity in human NASH. This study evaluated the in vivo activities of multiple CYP isoforms simultaneously in prominent diabetic NASH mouse models. The pharmacokinetics of CYP selective substrates: caffeine, losartan, and omeprazole changed significantly in a diabetic NASH mouse model, indicating attenuation of the activity of Cyp1a2 and Cyp2c29, respectively. Decreased mRNA expression of Cyp1a2 and Cyp2c29, as well as an overall decrease in CYP protein expression, was found in the diabetic NASH mice. Overall, these data suggest that the diabetic NASH model only partially recapitulates the human ex vivo CYP alteration pattern. Therefore, in vivo determination of the effects of NASH on CYP activity should be conducted in human, and more appropriate models are required for future drug metabolism studies in NASH.

Mammalian telomeres are nucleoprotein complexes at the end of chromosomes containing a specific protein complex, called shelterin. Shelterin protects chromosome ends from the DNA damage response (DDR), by facilitating the formation of a telomeric capping structure, called the T-loop. During their elongation in S phase, telomeres become transiently uncapped and can be sensed as DNA damage in G2 phase. This leads to the recruitment of DDR factors, such as phosphorylated histone H2AX (γH2AX), to the telomeres forming the so-called, telomere dysfunction-induced foci (TIFs). My PhD work described here, indicates that DNA damage occurring during interphase can persist after entry into mitosis, indicated by the detection of γH2AX at a subset of mitotic telomeres in human and mouse cells. This accumulation of γH2AX to mitotic telomeres is ATM-dependent and the γH2AX-labelled uncapped telomeres that persist, are shorter than the average telomere length for the entire cell population. Most importantly, my work suggests that telomere uncapping, naturally occurring or artificially induced, is detected by two parallel ATM/ATR-dependent pathways at the G2/M transition: a p53/p21-dependent pathway through the ATM/ATR-mediated phosphorylation of p53 at Ser15 and a CHK1/CHK2-dependent pathway that acts through negative regulation of CDC25 phosphatases. In particular, telomere uncapping triggered by TRF2 depletion leads to CHK2-dependent CDC25A degradation, while POT1 depletion results in CHK1-mediated CDC25A and CDC25C degradation. Both pathways act as sensors of unprotected telomeres at the G2/M transition and block cell cycle progression through inhibition of CDK1/Cyclin B complex, allowing telomere re-capping before entry into mitosis. This mechanism protects telomere integrity by the maintenance of a cell cycle stage conducive for capping reactions and thereby prevents genomic instability induced by telomere dysfunction. Finally, I studied the cellular functions of 3 poorly characterised shelterin components, TRF1, RAP1 and TPP1, in telomere protection. TRF1 and to a lesser extent RAP1 were shown to be important for telomere protection by suppressing DDR at the telomeres, while TPP1 was shown to be mainly responsible for the recruitment of the catalytic subunit of telomerase, TERT , to the chromatin, contributing to telomere maintenance. In conclusion, my work on both human and mouse models, reveals an important part of the DDR pathways activated by dysfunctional telomeres, as well as the molecular mechanisms underlying the cell cycle specific regulation of telomere capping, which ensures that only cells with intact telomeres enter mitosis.