Interação entre angiotensina-(1-7) [Ang-(1-7)] e bradicinina (BK) foi determinada no mesentério de ratos Wistar anestesiados utilizando-se microscopia intravital. Aplicação tópica de BK e Ang-(1-7) induziram vasodilatação que foi abolida por HOE-140 e A-779, respectivamente. Ang-(1-7) (100 pmol) potencializou a vasodilatação de BK (1 pmol) mas não a vasodilatação promovida por acetilcolina, nitroprussiato de sódio, histamina e ácido araquidônico. O efeito potencializador de Ang-(1-7) sobre BK foi abolido por A-779, HOE-140, indometacina, L-NAME e TEA, entretanto, losartan não bloqueou este efeito. Enalaprilato aumentou a resposta vasodilatadora de BK e Ang-(1-7) e não alterou o efeito potencializador do segundo sobre o primeiro. Conclui-se que: 1)efeito potencializador de Ang-(1-7) sobre BK depende da interação de ambos com seus respectivos receptores; 2)é dependente de óxido nítrico, produtos da cicloxigenase e hiperpolarização de membrana via canais de potássio; 3) o mecanismo de potencialização parece não depender da atividade catalítica da ECA. / The interaction between angiotensin-(1-7) [Ang-(1-7)] and bradykinin (BK) was determined in the mesentery of anesthetized Wistar rats using intravital microscopy. The response-induced by topical application of BK (1, 10 and 30 pmol), Ang-(1-7) (1, 10, 100 and 1000 pmol) and Ang-(1-7) (100 pmol) + BK (1 pmol) was determined in mesenteric arterioles (15-20 mm diameter). The BK (1 pmol)- and Ang-(1-7) (100 pmol)- induced vasodilation was abolished by BK B2 receptor antagonist HOE-140 (100 pmol applied during 60 seconds) and the Ang-(1-7) antagonist [d-Ala7]-Ang-(1-7)] (A-779) (100 pmol applied during 15 seconds), respectively. Indomethacin (5 mg/kg; IM, 30 min before), a cyclooxygenase inhibitor; L-NAME (10 nmol; topical application, 3 min before), a NO synthase inhibitor, decreased the Ang-(1-7)-induced vasodilation. However, TEA (90 pmol; topical application), a non specific K+ channels blocker, did not alter the response to BK or Ang-(1-7). BK (1 pmol)-induced vasodilation, however, was potentiated by Ang-(1-7) 100 pmol. Sodium nitroprusside (38 pmol), acetylcholine (1,6 nmol), histamine (5,4 nmol) and arachdonic acid (10 nmol) responses were not modified by Ang-(1-7) 100 pmol. The Ang-(1-7)-potentiating effect on BK-induced vasodilation was abolished by A-779, HOE-140, indomethacin, L-NAME and TEA. Losartan (15 mg/kg.IV, 40 min before), an AT1 angiotensin receptor antagonist was without effect. On the other hand, enalaprilat treatment (10 mg/kg; IV, 30 min before), to inhibit angiotensin-converting enzyme (ACE), enhanced the BK and Ang-(1-7)-induced vasodilation but did not modify the effect of Ang-(1-7) on BK vasodilation. In conclusion, the potentiation of BK-induced vasodilation by Ang-(1-7) is a receptor-mediated phenomenon dependent on cyclooxygenase-related products, NO release and K+ channel-mediated membrane hyperpolarization. The potentiating mechanism, apparently, is not related to ACE catalytic activity.

This diploma thesis deals with topic of cochlear implants (CI), especially with elaborating of sound signal with audio processors. In this work, principles and possibilities of rehabilitation of hearing with cochlear implants are described. In the thesis, there are principles of audio processors and modern coding strategies explained. The processes of simulation of selected strategies are stated. In the last chapter, there are the results of the simulations tested and discussed.

School-age children are at high risk of experiencing traumatic and stressful events that can negatively impact their academic, emotional, and behavior performance (Brock et al., 2016). Any stressful situation (i.e., natural disaster) or adverse childhood experience (ACE) can potentially become a traumatic event for a child or adolescent. The current literature indicates that 60% of children experience at least one ACE, putting them at high risk for a variety of health and social problems (Manyema et al., 2018). Natural disasters adversely impact children's life as they have the potential to destroy physical structures and injure the child or family members. According to Inoue and colleagues (2018) natural disasters can additionally be considered as an ACE. The purpose of this study was to explore the relationship between PTSD symptoms of students who have experienced a natural disaster (e.g., hurricane exposure) and students’ internalizing and externalizing behaviors. Participants included 75 students from elementary, middle, and high school in a school district in the Southeastern United States. Linear regression showed that PTSD symptoms are significantly correlated with internalizing and externalizing behaviors. However, moderation and interaction effects showed that he type of hurricane exposure did not significantly moderate the relationship between PTSD symptoms and students' internalizing and externalizing behaviors. Implications from these results suggest that trauma-informed strategies are needed for students that are exposed to a traumatic event.

<p>  </p> <p>The ever-growing interest in novel food ingredients and their dietary influence on human health and wellbeing has driven the study of bioactive peptides (BAP). BAP are protein-derived fragments composed of (2-20 amino acids) that could positively affect bodily function and chronic diseases. This dissertation explores the health-promoting properties of a novel source of BAPs, namely canary seed, by encompassing three specific aims: 1) evaluate the <em>in vitro </em>potential of hairless canary seed peptides (CSP) as a nutraceutical ingredient, 2) develop an understanding of CSP's bioavailability and molecular interactions with its biological targets, and 3) evaluate CSP's antioxidant and antiobesity activity at the organism level using a nematode (<em>C. elegans</em>) and murine (C57BL/6J mice) model, respectively. First, CSP were generated by implementing mechanical oil extraction followed by commercial enzymatic hydrolysis with Alcalase™. In addition, CSP were also subject to simulated gastrointestinal digestion (SGD) to assess their gastric stability and <em>in vitro</em> bioavailability. The results showed that canary seed proteins were mainly composed of prolamins fractions followed by glutelins, globulins, and albumins. CSP extracts with low molecular weight (< 3 kDa and 3–10 kDa) showed the highest bioactivity. Furthermore, after SGD, CSP inhibitory activity remained stable toward angiotensin-converting enzyme (ACE), dipeptidyl peptidase IV (DPP-IV), and pancreatic lipase but unstable for α-glucosidase. The digested peptides were transported efficiently (>10%) through the Caco-2 monolayer, indicating a potential high absorption capacity through the intestinal epithelium. During kinetic analysis by Lineweaver-Burk plots, it was observed that CSP-SGD interacted by mixed-type inhibition for DPP-IV and α-glucosidase, non-competitive inhibition for ACE, and uncompetitive inhibitor for pancreatic lipase. Furthermore, CSP-SGD were especially potent as antihypertensive (ACE inhibitors) and antiobesity (pancreatic lipase) agents. Consequently, molecular docking and <em>in silico</em> analyses were targeted to understand CSP-SGD interactions with ACE and pancreatic lipase. CSP-SGD with ACE inhibitory activity were found to be rich in proline, glutamine, and cationic residues and could have inhibited ACE by destabilizing the tetrahedral transition state and zinc ions interaction leading to conformational changes in the enzyme structure. For peptides with antiobesity properties, it was also found that arginine, glycine, and hydrophobic amino acids from CSP-SGD hold critical interactions with the lid domain (CYS238-CYS262) of pancreatic lipase, disrupting its proper function and preventing fat hydrolysis.</p> <p>In the second part of this dissertation, the relevant health-promoting properties of CSP were further investigated by testing the effects of peptide supplementation on obesity and oxidative stress animal models. The studies showed that exposure to CSP significantly mitigated the acute and chronic oxidative damage in <em>C. elegans</em>, extending the lifespan of the nematodes by 88 and 61%, respectively. Furthermore, it was established that the CSP prevented oxidative stress by scavenging free radicals and antioxidant gene upregulation. Concerning this, CSP caused a drop in reactive oxygen species (ROS) to safe levels and induce the upregulation of the GST-4 gene encoding antioxidant enzyme Glutathione S-transferase. Concerning antiobesity properties, the daily supplementation with CSP successfully prevented metabolic implications of western diet-induced obesity in C57BL/6J mice, including preventing weight gain by up to 20%, increasing glucose tolerance, and reducing insulin, leptin, and LDL/VLDL levels in plasma. Likewise, CSP promoted a drop in fatty acid uptake gene, LPL, and fatty acid biosynthesis genes FAS and ACC while unaffecting lipid oxidation genes PPAR-α and ACO in the liver. While both moderate and high CSP supplementation levels exhibit hypolipidemic effects, only moderate levels induce satiety and significantly prevent weight gain. Together, these results suggest that CSP's weight gain prevention depended on a dual mechanism involving lipid metabolism retardation to modulate satiety. Overall, the results presented in this dissertation establish the effectiveness of canary seed peptides as nutraceutical ingredients for antioxidant and antiobesity functional food applications.</p>

Adult depression is a common consequence of adverse childhood experience. There is also a higher likelihood of being affected by economic burdens after having expierienced a traumatic event in childhood. As depression has been associated with economic burden, these long-term sequelae of childhood adversity are likely to interact. We investigated depression and economic consequences, such as unemployment, lower level of education, lower income as long term sequelae of adverse childhood experiences in adulthood and their interaction. Childhood Maltreatment was measured by the German version of the Adverse Childhood Experience (ACE) questionnaire. Depression was measured by the Patient Health Questionnaire (PHQ-2). Logistic regressions were applied to investigate the risks of suffering economic burdens, with depression as a moderator. Depressive symptoms increased with the number of ACEs and were highest in those reporting four or more ACEs, especially amongst those who experienced sexual and emotional abuse, as well as neglect. Moderation analysis showed a significant effect of depression incresing almost all economic burdens. Migration background additionally increased the risk of unemployment and working in a blue-collar job. Female gender decreased the risk of unemployment and working in a blue-collar job, but increased the risk of low income and part-time employment. The moderation effect of depression increased the negative impact of exposure to multiple ACEs on economic life in adulthood. Prevention of ACEs and early intervention are needed to prevent the mental health and economic consequences.

No description available.

Bakgrund: Elever upplever traumatiska barndomsupplevelser (TBU) som påverkar förmågan att hantera livet som barn och vuxen. Det är angeläget att upptäcka och identifiera elever med TBU eftersom de har rätt till skydd, rehabilitering och social återanpassning. Uppgiften är central i skolsköterskans hälsofrämjande roll. Syfte: Undersöka hur skolsköterskor arbetar med att upptäcka och identifiera traumatiska barndomsupplevelser hos elever. Metod: En retrospektiv enkätstudie användes och 100 skolsköterskor lämnade sina svar mellan 20 februari och 21 mars. Nästan alla hade specialistsjuksköterskeutbildning. Resultat: Frågor om TBU ställdes av 66 % och 34 % gjorde det inte. Majoriteten frågade muntligt. Frågan om TBU fanns i skolans hälsoenkät hos 38 % och en använde validerade formulär för att upptäcka och identifiera TBU. Av samtliga respondenter ville 78 % lära sig använda Barnafrids validerade formulär för att upptäcka och identifiera TBU. Konklusion: Många frågar om TBU men en tredjedel gör det inte. Mindre än hälften hade frågor i skolans hälsoenkät. Få kände till att validerade formulär kunde hjälpa till i arbetet med TBU och användes av en. Skolsköterskor, vårdgivare, lärosäten och forskare kan tillsammans utveckla systematisk screening av TBU. Det främjar elevers hälsa, välbefinnande och möjlighet att nå utbildningens mål. / Background: Students experience adverse childhood experiences (ACE) that affect the ability to cope with life as a child and as an adult. It's important to detect and identify ACE because students have the right to protection, rehabilitation and social reintegration. This task is central for school nurse’s health promoting role.  Aim: To investigate how school nurses’ work to detect and identify ACE in students.  Method: A retrospective survey study was used and 100 school nurses provided their responses between 20 February and 21 March. Almost all had specialist nursing training.  Findings: Questions about ACE were asked by 66% and 34% did not. A majority asked verbally. ACE questions was present in 38 % of the school health questionnaire. One used validated form and of all 78% wanted to learn how to use validated form to detect and identify ACE.  Conclusion: School nurses ask about ACE but a third do not. Less than half had questions in the school health questionnaire and few knew that validated forms could help in the work with ACE. School nurses, healthcare providers, universities and researchers can together develop systematic screening for ACE. It promotes students' health, wellbeing and the opportunity to reach the goals of the education.

Thesis (M.Pharm. (Pharmacy Practice))---North-West University, Potchefstroom Campus, 2008.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

Avec quatorze anticorps utilisés en oncologie, les anticorps monoclonaux ont enfin une place de choix dans l'arsenal thérapeutique anticancéreux. Cependant, l'un des modes d'action les plus importants de ces molécules, la cytotoxicité à médiation cellulaire dépendante des anticorps (ADCC), souffre de plusieurs limites en raison de la nécessité d'une interaction optimale avec le Fc&#947;RIIIA. L'équipe du Dr. Daniel Baty a conçu de nouveaux formats d'anticorps bispécifiques basés sur l'utilisation de domaine unique d'anticorps de lamas (sdAb) et capables de contourner la plupart de ces limites. Des banques de phages issus de lamas immunisés ont permis de sélectionner deux sdAbs (d'affinités différentes) dirigés contre le Fc&#947;RIIIA exprimé par des cellules NK et les macrophages, ainsi qu'un sdAb dirigé contre l'antigène tumoral carcino-embryonnaire (ACE). En utilisant les domaines CH1 et Ck d'IgG1 humaine comme motif d'hétérodimérisation et les sdabs anti-ACE et anti-Fc&#947;RIII précédemment sélectionnés, nous avons développé des formats innovants d'anticorps bispécifiques Fab-like nommés bsFabs. Ces molécules sont faciles à produire, très stables et peuvent déclencher la lyse des cellules tumorales par les cellules NK humaines à des concentrations de l'ordre du picomolaire. Elles ne se lient pas au récepteur inhibiteur Fc&#947;RIIB, n'entrent pas en compétition avec des IgG sériques pour la liaison aux récepteurs, et leur activité cytotoxique est indépendante de la glycosylation du Fc et du polymorphisme du Fc&#947;RIIIA. / With fourteen antibodies used in oncology, monoclonal antibodies finally have a place in the therapeutic arsenal against cancer. However one of the modes of action of the most important of these molecules, cell-mediated cytotoxicity antibody-dependent (ADCC), suffers from several limitations due to the need for optimal interaction with the Fc&#947;RIIIA. Daniel Baty's team has developed new formats of bispecific antibodies based on the use of single domain llama antibodies (SdAb) that are capable of circumventing most of the these limitations. Phage libraries from immunized llamas were used to select two sdAbs directed against the Fc&#947;RIIIA expressed by NK cells and macrophages (with different affinities for Fc&#947;RIII), as well as one SdAb directed against the tumor antigen carcinoembryonic (CEA). Using CH1 and Ck domains of human IgG1 as a motif for heterodimerization and sdabs previously selected, we have developed innovative anti-CEA and anti-Fc&#947;RIII formats of bispecific antibodies Fab-like named bsFabs. These molecules are easy to produce, very stable and can trigger tumor cell lysis by human NK cells at picomolar concentrations. They do not bind Fc&#947;RIIB inhibitory receptor, do not compete with serum IgG and their cytotoxic activity is independent of Fc&#947;RIIIA polymorphism. In addition, they slow tumor growth in mouse model. In terms of pharmacokinetics, although bsFabs have a reasonable tumor retention, one of the limitations of these formats is size, which leads to rapid renal elimination. Such findings led us to consider the creation of new antibody formats to both increase tumor retention and secondly the half-life of antibodies in the body.