La présente étude vise à étudier le potentiel de bifidobactéries à protéger les cellules contre l’infection par le Coxsackie B4 (CV-B4). Le criblage de bifidobactéries a identifié deux des cinq souches qui protégeaient les cellules HEp-2 lorsque les bifidobactéries sont pré-incubées avec les particules virales avant l'inoculation sur les cellules Hep-2. En revanche, aucun effet protecteur n'a été observé en incubant les cellules Hep-2 avec des bifidobactéries avant l'inoculation de CV-B4. Les lipoprotéines des parois cellulaires (LpAs) sécrétées par les souches sélectionnées sont testées pour leur activité antivirale. Les deux LpAs présentaient une activité antivirale quand ils sont incubés avec les particules virales avant d’être inoculées aux cellules HEp-2. Aucun effet protecteur n'a été induit par incubation des LpAs avec les cellules HEp-2 avant l'inoculation de CV-B4. La protéine recombinante présente une activité antivirale identique. Pour identifier les séquences peptidiques interagissant avec les particules virales, les protéines de LpAs sont alignées avec les séquences peptidiques du nord bord du canyon et avec l’empreinte de la région puff sur le Coxsackievirus et sur le récepteur de l’adénovirus (CAR). L'étude d'amarrage moléculaire in silico (Docking) utilisant le CV-B3 en tant que modèle a montré une faible énergie de liaison indiquant un système stable pour les peptides sélectionnés et par conséquent une interaction probable avec le CV-B. Les peptides de B.longum et de B.breve qui sont homologues à l’empreinte du rebord nord viral sur la séquence CAR, forment des liaisons d’hydrogène avec plusieurs résidus viraux dans la région du rebord nord du canyon, qui sont déjà décrits pour leur interaction avec le CAR.En conclusion, les protéines de LPAS bifidobactéries peuvent inhiber l'infection par le CV-B4 probablement par liaison aux acides aminés de la capside qui interagissent avec le CAR. / The present study aims at investigating the potential of bifidobacteria in protecting cells from Coxsackievirus B4 (CV-B4) infection. The bifidobacterial screening identified two out of five strains that protected HEp-2 cell viability when bifidobacteria were incubated with the viral particles prior inoculation. In contrast, no effect was shown by incubating HEp-2 cells with bifidobacteria prior CV-B4 inoculation. Cell-wall lipoproteins secreted by the selected strains (LpAs) were assayed for their anti-viral activity. The two LpAs exhibited anti-viral activity when they were incubated with the viral particles prior inoculation to HEp-2 cells. No effect was induced by incubating LpAs with HEp-2 cells prior CV-B4 inoculation. The recombinant LpAs derived-protein exhibited identical anti-viral activity. To identify the peptide sequences interacting with the virus particles, LpAs proteins were aligned with the peptide sequences of north canyon rim and puff footprint onto coxsackievirus and adenovirus receptor (CAR). The in silico molecular docking study using CV-B3 as template showed a low energy binding indicating a stable system for the selected peptides and consequently a likely binding interaction with CV-B. B.longum and B.breve peptides homologous to the viral north rim footprint onto CAR sequence formed hydrogen bonds with several viral residues in the north rim of the canyon, which were already predicted as interacting with CAR. In conclusion, proteins from bifidobacterial LpAs can inhibit the infection with CV-B4 likely through binding to the capsid aminoacids that interact with CAR.

Le gène Arntl2 (Aryl hydrocarbon Receptor Nuclear Translocator-Like 2) sur lequel travaille notre laboratoire est un facteur de transcription lié au rythme circadien qui a été identifié comme un gène candidat au diabète de type 1. Parmi les gènes régulés par ce facteur de transcription se trouvait un excellent gène candidat, l’interleukine-21, responsable de la prolifération des lymphocytes T CD4+, en partie responsable de la destruction des cellules β du pancréas dans le diabète. Mon projet de thèse a donc consisté à étudier comment les allèles NOD et C3H d’Arntl2 contrôlaient l’expression d’Il-21, en quoi cela affectait le système immunitaire dans son ensemble. L’analyse des composantes immunitaires a montré que les souris avec un allèle C3H en Idd6.3 produisent moins de cellules T CD4+, CD8+ et CD4+IL-21+ comparées aux souris avec un allèle NOD en Idd6.3 et NOD.B6 Arntl2-/-. Nous avons pu démontrer que cette différence est due au fait qu’ARNTL2 se lie de façon spécifique au site de liaison de l’ARN polymérase 2 du promoteur d’Il-21 et inhibe son expression. Nous avons également démontré que la non fonctionnalité de ce gène conférait une augmentation de la résistance à l’apoptose des thymocytes. D’autres tests ont révélés que cette résistance à l’apoptose passait par IL-21, en effet des injections de cette cytokine apportaient la même augmentation de la résistance que celle trouvée dans les lignées ne disposant pas d’une version fonctionnelle d’Arntl2. Ces nouveaux résultats mettent en avant un rôle inattendu d’Arntl2 dans l’équilibre immunitaire par son contrôle de l’expression d’Il-21 ainsi que dans la sélection thymique des cellules T par le biais de l’apoptose. / The Arntl2 gene (Aryl hydrocarbon Receptor Nuclear Translocator-Like 2) on which our lab focus is a transcription factor linked to the circadian rhythm which has been identified as a candidate gene to type 1 diabetes. Amongst the genes regulated by this transcription factor there is a strong candidate gene: the Interleukin 21, responsible of the proliferation of the T CD4+ lymphocyte, contributing to the destruction of the β cells in the pancreas during type 1 diabetes. My thesis project consisted on studying how the NOD and C3H alleles of Arntl2 control the expression of Il-21 and how it affected the immune system. The analysis of the immune cells revealed that the mice with a C3H allele in Idd6.3 produce less CD4+, CD8+ and CD4+IL-21+ T cells than the mice with a NOD allele in Idd6.3 and the NOD.B6 Arntl2-/-. We showed that this difference is due to the fact that ARNTL2 binds specifically to the RNA POL II binding site on the Il-21 promoter and inhibits its expression. We also have shown that a Knockout of this gene increase the apoptosis resistance of the thymocytes. And that this resistance was due to IL-21, indeed, injections of IL-21 brought the same increase in resistance than the one in the strains without a functional version of Arntl2. These new results show an unexpected role for Arntl2 in the regulation of the immune equilibrium by its control of Il-21 expression, and in the thymic selection of T cell by apoptosis.

Aerobic exercise interventions involving individuals with type 1 diabetes have had little positive effect on blood glucose control as reflected by hemoglobin A1c. The few existing interventions involving resistance exercise, either alone or combined with aerobic exercise, while small in sample size, have had better outcomes. The purpose of this research program was to examine the changes in blood glucose levels during activity and for 24 hours post-exercise (as measured by continuous glucose monitoring) when resistance exercise is performed, either on its own or combined with aerobic exercise, as compared to aerobic exercise alone or no exercise. Twelve physically active individuals with type 1 diabetes performed 5 separate exercise sessions in random order separated by at least five days: 1) no exercise/control; 2) aerobic exercise (45 minutes of treadmill running at 60% VO2peak); 3) resistance exercise (45 minutes of weight lifting – 3 sets of 8 repetitions of 7 different exercises); 4) aerobic then resistance exercise (2 and 3 combined with the aerobic exercise first); 5) resistance then aerobic exercise (2 and 3 combined with the resistance exercise first). We found that resistance exercise was associated with a lower risk of hypoglycemia during exercise, less carbohydrate intake during exercise, less post-exercise hyperglycemia and more frequent (but less severe) nocturnal hypoglycemia than aerobic exercise. When aerobic and resistance exercise were combined, performing resistance exercise prior to aerobic exercise (rather than the reverse) resulted in attenuated declines in blood glucose during aerobic exercise, accompanied by a lower need for carbohydrate supplementation during exercise and a trend towards milder post-exercise nocturnal hypoglycemia.

Type 1 diabetes (T1D) is an autoimmune disease whereby the insulin-producing β-cells of the pancreas are destroyed by the immune system, possibly related to an inappropriate immune reaction to dietary antigens and/or microbes in the gut. We previously observed a deficit in gut-resident CD163+ M2 anti-inflammatory macrophages in BioBreeding diabetes-prone (BBdp) rats. Heme oxygenase-1 (HO-1) is the rate-limiting enzyme of the CD163 pathway and through the breakdown of toxic heme releases potent antioxidants. We hypothesized that the treatment of animals with cobalt protoporphyrin (CoPP), an inducer of HO-1 expression, would inhibit development of T1D through modulation of the CD163/HO-1 pathway and increase M2 macrophages. HO-1 expression was significantly increased in the pancreas and gut. T1D incidence was inhibited in CoPP-treated rats and these animals showed an unexpected increase in cells expressing CD68 (an M1 pro-inflammatory macrophage marker) in the pancreas and gut. CoPP induced the expression of cathelicidin anti-microbial peptide (CAMP) in the jejunum, which co-localized with CD163+ (M2) macrophages. KLF4, an M2 macrophage-specific transcription factor, was significantly upregulated in the pancreas and jejunum of CoPP-treated animals and co-localized with CD68 and HO-1 in the pancreas. We conclude that HO-1 induction prevented T1D through modulation of the gut immune system and potential recruitment of a unique population of anti-inflammatory M2 macrophages in the gut and pancreas

Orientador: Maria Luiza Silveira Mello / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-22T06:29:06Z (GMT). No. of bitstreams: 1 Ghiraldini_FlaviaGerelli_D.pdf: 75704253 bytes, checksum: 9d1afc3cebcffd05000b5efb25d3996d (MD5) Previous issue date: 2013 / Resumo: O diabetes mellitus do tipo I (DM1) caracteriza-se pela ocorrência de insulite com consequente hiperglicemia e poliuria. Alterações celulares estruturais e metabólicas decorrentes do aumento da glicemia podem provocar fenótipos de envelhecimento precoce. O envelhecimento celular e resultado de fatores intrínsecos e extrínsecos, que alteram a estrutura e a organização da cromatina e que, consequentemente, afetam a expressão gênica. As sirtuinas, deacetilases NAD+-dependentes, estão envolvidas na transcrição gênica, reparo de DNA, transcrição do rDNA, regulação metabólica e remodelação cromatinica. As sirtuinas nucleares, especialmente Sirt1 e Sirt6 estão envolvidas com o envelhecimento precoce, no metabolismo de glicose e na resposta a inflamação. O presente trabalho teve como objetivo geral comparar os processos de remodelação cromatinica em hepatocitos sob o efeito da hiperglicemia e do envelhecimento, usando-se modelo animal (camundongos). Um modelo de cultura celular (HepG2) foi também utilizado para estudo de efeitos da hiperglicemia, utilizando-se como metodologias analisem morfológicas e moleculares. Foi observado um aumento em conteúdo de DNA e em acessibilidade da cromatina a MNase mais acentuado em hepatocitos de animais DM1 do que de idosos. O aumento na abundancia de Sirt1 em animais hiperglicêmicos não refletiu em sua maior atividade, enquanto em idosos houve um decréscimo generalizado nesses parâmetros e aumento da aceptilação de sítios histónicos. Em animais DM1, Sirt6 apresentou abundancia semelhante à de Sirt1, possivelmente devido à alta fragmentação de DNA observada nesses animais, diferente do ocorrido em idosos. Ambos os animais DM1 e idosos apresentaram baixa relação área AgNOR+/área nuclear. Em animais diabéticos isto foi devido ao aumento na área nuclear, enquanto nos idosos, foi devido à diminuição na área AgNOR+ e aumento na área nuclear. O aumento na metilação de rDNA na porção 18S e a baixa abundancia de Sirt7 confirmam diminuição no metabolismo celular no envelhecimento. Em hepatocitos de camundongos DM1 e idosos foi observado genes diferencialmente expressos relacionados à inflamação. Admite-se que no primeiro caso este achado seja devido à natureza auto-imune da doença, enquanto no segundo possa ser um indício de inflamação naturalmente encontrada em processos de envelhecimento. Em animais DM1, a expressão diferenciada de genes envolvidos com metabolismo de lipídios poderia contribuir para com a peroxidação lipídica e produção de ROS levando a esteatose hepática. Nas células HepG2, alterações na expressão dos genes Apoe, Igfbp1 e Foxo1, ocorridas em meio de cultura hiperglicêmicas, tornaram-se revertidas quando as células foram retornadas a normoglicemia. Contudo, as abundancias das marcações epigenéticas nos promotores desses genes decresceram progressivamente, indicação de uma memória hiperglicêmica, dado não observado em modelo animal. A análise do fenótipo nuclear dessas células indicou possível indução da proliferação celular quando retornadas a normoglicemia. A inibição de sirtuinas aumentou o conteúdo Feulgen-DNA e o contraste entre cromatina condensada e não-condensada, indicativo de atuação na proliferação celular e na remodelação cromatinica. DM1 e envelhecimento, portanto, não podem ser considerados fenômenos idênticos, pois enquanto no primeiro ha um mecanismo compensatório que promove alterações genéticas, epigenéticas e remodelação cromatinica, no segundo ha um decréscimo generalizado no metabolismo celular levando a modificações diferentes nos mesmos parâmetros / Abstract: Diabetes mellitus type I (DM1) is characterized by insulitis and consequent hyperglycemia and polyuria. Structural and metabolic changes in the cell caused by hyperglycemia might induce an early-ageing phenotype. Both intrinsic and extrinsic agents might contribute to cellular ageing thus leading to chromatin structural changes and differential gene expression. Sirtuins, NAD+-dependent deacetilases, play a role in cell metabolism, transcription, DNA repair and chromatin remodeling. Sirt1 and Sirt6, especially, are nuclear proteins related to early-ageing, glucose metabolism and inflammatory response. The general purpose of the present work was to compare processes of chromatin remodeling in hepatocytes under the effects of hyperglycemia and aging, using mouse models. A model using cells in culture (HepG2) was also used to study the effects caused by hyperglycemia. The methodology used involved morphological and molecular analysis. An increase in DNA content and chromatin accessibility to MNAse was found more pronounced in hepatocytes from DM1 than from aged mice. Despite the high abundance of Sirt1 in DM1 animals, its activity was not proportionally high, whereas in old animals there was a reduction in these parameters, increasing the acetylation of Sirt1-histonic sites. In DM1 mice, Sirt6 presented similar abundance as Sirt1, possibly due to the high DNA fragmentation, different to what was found in aged animals. Both DM1 and normoglycemic old mice presented a decrease in AgNOR+ area/nuclear area ratio. While in DM1 animals it was a result from the increase in nuclear area, in old animals it was a combination of increased nuclear areas and decreased AgNOR+ areas. The DNA methylation increase in the 18S rDNA region and the decrease in Sirt7 abundance in the hepatocytes from old mice support the hypothesis of diminished cellular metabolism. Differential expression analysis for DM1 and old mouse hepatocytes presented a high number of genes involved in the inflammatory response. While in the former it could be an autoimmune characteristic of the disease, in the latter it might be an evidence of inflammatory state naturally associated with aging. Moreover, DM1 mice also presented differential gene expression related to lipid metabolism, which could contribute to increase lipid peroxidation and ROS production leading to hepatic steatosis. HepG2 cells showed changes in Apoe, Igfbp1 and Foxo1 expression in hyperglycemic medium and they were reverted when the cells returned to normoglycemic medium. The epigenetic marks, however, presented a progressive decrease in abundance, indicative of a hyperglycemic memory, which was not observed in DM1 animals. The nuclear phenotype in HepG2 cells under these same experimental conditions indicated a possible induction in cellular proliferation when the cells were returned to the normoglycemic medium. Inhibition of sirtuins increased the contrast between condensed and non-condensed chromatin and the Feulgen-DNA content, indicating a role in cell division and chromatin remodeling. Therefore, DM1 and ageing cannot be considered as identical processes, because while in DM1 there is a compensatory mechanism that induces changes in epigenetic marks, chromatin remodeling and differential gene expression, there is a general decrease in cell metabolism under aging that leads to different changes in the same parameters / Doutorado / Biologia Celular / Doutor em Biologia Celular e Estrutural

Bakgrund: Diagnostiserade fall av personer med typ 1-diabetes ökar globalt och komplikationer kan uppstå i samband med sjukdomen. Lågkolhydratkost har visat sig vara en potentiell metod för att förbättra blodsockerreglering. Sjuksköterskor ansvarar för kostrådgivning och därav behövs mer kunskap om ämnet då det vetenskapliga underlaget är otillräckligt. Syfte: Uppsatsens syfte var att undersöka påverkan av lågkolhydratkost hos personer med typ 1-diabetes. Metod: En litteraturstudie av 10 vetenskapliga artiklar genomfördes med en induktiv ansats. Resultat: Följande huvudkategorier presenterades i studiens resultat: kroppsliga förändringar och upplevelser. Underkategorierna var: blodsocker, insulin, blodfetter, ketoner, vikt och BMI, vitalparametrar, positiva erfarenheter och utmaningar. Effekter av lågkolhydratkost varierade avseende blodsocker, insulin, blodfetter, vikt och blodtryck. BMI förbättrades, ketonnivåer höjdes och diabetes ketoacidos förekom i samband med lågkolhydratkost. Erfarenheter av lågkolhydratkost varierade. Konklusion: Sjuksköterskor och sjuksköterskestudenter behöver information om lågkolhydratkost och typ 1-diabetes. På så sätt kan adekvat information, evidensbaserad vård och personcentrerad vård erbjudas till personer med typ 1- diabetes. / Background: Diagnosed cases of people with type 1 diabetes are growing globally and complications can occur in correlation with the disease. Low carbohydrate diets have shown to be a potential method to improve blood sugar regulation. Nurses are responsible for dietary advice and therefore more knowledge is needed on the subject as the scientific basis is insufficient. Aim: The aim of this thesis was to examine the impact of a low carbohydrate diet for people with type 1 diabetes. Method: A literature study of 10 scientific articles was conducted with an inductive approach. Results: The following main categories was presented: bodily changes and experiences. The subcategories were: blood sugar, insulin, blood fats, ketones, weight and BMI, vital parameters, positive experiences and challenges. The effects of low carbohydrate diets varied regarding blood sugar, insulin, blood fats, weight and blood pressure. BMI improved, ketone levels were raised, diabetic ketoacidosis occurred and experiences with a low-carbohydrate diet varied. Conclusion: Nurses and nursing students need information about low carbohydrate diets and type 1 diabetes. In this way adequate information, evidence-based care and person-centered care can be offered to people with type 1 diabetes.

Bakgrund: Långvarig sjukdom innebär en förändrad vardag på många sätt. Det behövs resurser för att hantera och acceptera sjukdomen för att uppnå en överkomlig vardag. Diabetes typ 1 är en av de snabbast växande kroniska sjukdomarna i världen och det finns cirka 1,1 miljoner barn med sjukdomen. Föräldrarna har viktig roll i deras omvårdnad. Familjefokuserad omvårdnad innebär att lägga fokuset på omvårdnad på hela familjen och inte enbart patienten. En stor roll hos sjuksköterskan är att ha ett bra samspel mellan alla involverade i familjen. Syfte: Syftet var att beskriva föräldrars erfarenheter av att leva med ett barn med diabetes typ 1. Metod: En litteraturstudie har framställts med hjälp av 13 kvalitativa vetenskapliga artiklar, funna i databaserna PubMed och CINAHL. Huvudresultat: Tre huvudteman identifierades: Anpassning till den nya vardagen, Emotionella aspekter och Behov av stöd. Anpassning till den nya vardagen berörde erfarenheter hos föräldrar när barnet diagnostiserats med diabetes typ 1, rädslan för hypoglykemi och ge över ansvaret till andra. Emotionella aspekter handlade om vilka känslor som föräldrarna hade erfarenheter av under sjukdomens gång samt det stora orosmomentet, framtiden. Behov av stöd innefattade både hälso- och sjukvård och nära relationer, vilket påvisades hos föräldrarna som stort. Slutsats: Föräldrars erfarenheter var övergripande negativa, då de kände stor oro för sitt barn på grund av vad barnet fick utstå relaterat till sjukdomen. För föräldrarnas egen del kände de ett behov av större stöd från både hälso- och sjukvård och nära relationer. Detta är någonting som bör utvecklas inom en snar framtid, både för föräldrarnas och barnens upplevda hälsa. / Background: Long-term illness means a change of the daily life in many aspects. Resources are needed to manage and accept the disease in order to achieve an equitable everyday life. Type 1 diabetes is one of the fastest growing long-term illness in the entire world and there are approximately 1,1 million children with this illness. Parents are an important part in the care of the children. Family-based care means that the focus should be on caring for the entire family, not only for the patient. The nurse plays a great part in having to deal with the interplay between everyone involved in the family. Aim: The aim was to describe parents’ experiences of living with their child with type 1 diabetes. Method: A literature review has developed by using 13 qualitative studies, found in PubMed and CINAHL. Findings: Three main themes were identified: Adapting to the new daily life, Emotional aspects and Need of support. Adapting to the new daily life refered to parents’ experiences when their child were newly diagnosed, fear of hypoglycemia and transfer responsibility to others. Emotional aspects was about which emotions parents’ are dealing with throughout the illness, together with the big worry about the future. Need of support involves both healthcare and close relations, which were exposed as momentous to the parents. Conclusion: Parents’ experiences were overall negative, since they were worrying about their children and what they endured during their illness. The parents felt that a greater support system was necessary, both from the healthcare and from close relations. This is something that needs to be developed within a near future, both regarding parents’ and childrens’ perceived health.

Bakgrund: Omkring 900 barn och ungdomar insjuknar i typ 1-diabetes (T1D) varje år i Sverige, vilket gör den till en av landets vanligaste kroniska sjukdomar hos barn. Sjukdomen påverkar livet fysiskt och psykiskt och leder till allvarliga och potentiellt livshotande komplikationer om behandlingen inte sköts. Kunskap om sjukdomen är grunden för att behandlingen ska skötas optimalt, varför information och stöd från omgivningen och hälso- och sjukvården är av stor betydelse. Syfte: Syftet med denna litteraturstudie var att beskriva barn och ungdomars upplevelser av att leva med T1D. Metod: Litteraturstudie baserad på 12 kvalitativa originalartiklar hämtade från databaserna PubMed och CINAHL. Artiklarna har efter kvalitetsgranskning erhållit medelhög till högkvalitet. Resultatet har bearbetats och analyserat, därefter har huvudteman samt underteman identifierats. Resultat: Resultatet visade att barn och ungdomar med T1D upplevde många svårigheter. Sjukdomen innebar stora praktiska och psykosociala förändringar i vardagen och bidrog till flera negativa känslor samt oro gällande egenvård och komplikationer. Känslor av att vara annorlunda jämfört med jämnåriga var vanligt förekommande liksom känslor av ensamhet och utanförskap. Stödet från familj, vänner, skolpersonal samt hälso- och sjukvården var emellanåt bristfälligt men samtidigt viktigt och betydelsefullt och underlättade de negativa upplevelserna av att leva med T1D. Slutsats: Litteraturstudien visar på att barn och ungdomar med T1D möter svårigheter i vardagen och att sjukdomen påverkar livets fysiska som psykosociala aspekter. Sjukdomsförståelse och stöd från omgivningen har positiva effekter och underlättar livet förden drabbade. God kommunikation, ett personcentrerat förhållningssätt och gott bemötande från hälso- och sjukvården är andra faktorer som kan påverka sjukdomsupplevelsen positivt och bidra med de förutsättningar som krävs för att leva ett så gott liv som möjligt, trots sjukdom. / Background: About 900 children and adolescents are diagnosed with type 1 diabetes (T1D) every year in Sweden, which makes it one of the country's most common chronic diseases in children. The disease affects life physically and mentally and leads to severe and potentially life-threatening complications if left untreated. Knowledge of the disease is the key to successful treatment, which highlights the importance of information and support from a personal support system as well as the health care service. Aim: The aim of this literature review was to describe children and adolescents experiences of living with T1D. Method: A literature review based on 12 qualitative original articles retrieved from the databases PubMed and CINAHL. After quality analysis, the articles have been received medium to high quality. The results have been processed and analyzed, thereafter main themes and sub-themes were identified. Results: The results showed that children and adolescents with T1D experienced many difficulties. The disease involved major practical and psychosocial changes in everyday life and contributed to several negative emotions as well as concerns regarding self-care and complications. Feelings of being different from peers were common, as well as feelings of loneliness and exclusion. The support from family, friends, school staff and the health care service was sometimes deficient but at the same time important and significant and facilitated the negative experiences of living with T1D. Conclusion: This literature review shows that children and adolescents with T1D face difficulties in everyday life and that the disease affects the physical and psychosocial aspects of life. Understanding of the disease and support from the people in the child’s and adolescents surroundings has positive effects and makes life easier for the affected. Good communication, a person-centered approach and good treatment from the health care service are other factors that can positively affect the experience of T1D and contribute with the conditions required to live as good a life as possible, despite the disease.

Background and Purpose: Children diagnosed with Type 1 Diabetes face significant challenges in the day to day management of their disease. Parents play an important role in supporting children at every stage of their lives and helping them transition to independence in the management of T1D. The purpose of this study was to learn from parents who have raised their children with T1D to adulthood and identify strategies for parents who are currently raising a child with T1D. Methods: Using a biographical method, a qualitative design, two in-depth interviews with open-ended prompts were completed with purposively selected parents of children with Type 1 Diabetes (T1D) who have grown into adulthood (18 parents, 36 interviews). The first interview invited participants to share their experience raising a child with T1D. The second interview asked specific questions about challenges, things that went well, things that didn't go well and advice for parents currently raising a child with T1D. Qualitative content analysis was used. Results: Analysis of the data identified recommendations for parents currently raising children with T1D. Advice for the parents included, 1) Parental attitude toward diabetes will be reflected in the child – Keep it positive, 2) Learn as much as you can about diabetes, 3) Find a good diabetes provider – Make your endocrinologist your best friend, 4) Don't make diabetes the definition of the child – treat them as normal, 5) Empower self-management – Teach them along the way then step back and let them take over, 6) Be your child's advocate, 7) Find support – Formal or informal, 8) Listen to your child – Don't judge. Conclusions and Implications: Nurses and nurse practitioners can share strategies identified by parents that were helpful in raising their child with Type 1 Diabetes.

OBJECTIVE: Many youth do not use the hybrid closed-loop system for type 1 diabetes effectively. This study evaluated the impact of financial incentives for diabetes-related tasks on use of the 670G hybrid closed-loop system and on glycemia. METHODS: At auto mode initiation and for 16 weeks thereafter, participants received a flat rate for wearing and calibrating the sensor ($1/day), administering at least 3 mealtime insulin boluses per day ($1/day), and uploading ($5/week). Weekly bonuses were given for maintaining at least 70% of the time in auto mode, which were increased for persistent auto mode use from $3/week to a maximum of $13/week. If a participant failed to maintain auto mode for a week, the rewards were reset to baseline. Data from 17 participants aged 15.9 years ± 2.5 years (baseline hemoglobin A1c [HbA1c] 8.6% ± 1.1%) were collected at 6, 12, and 16 weeks. The reinforcers were withdrawn at 16 weeks, with a follow-up assessment at 24 weeks. RESULTS: With reinforcers, the participants administered an average of at least 3 mealtime insulin boluses per day and wore the sensor over 70% of the time. However, auto mode use waned. HbA1c levels decreased by 0.5% after 6 weeks, and this improvement was maintained at 12 and 16 weeks (P < .05). Upon withdrawal of reinforcers, HbA1c levels increased back to baseline at 24 weeks. CONCLUSION: Compensation for diabetes-related tasks was associated with lower HbA1c levels, consistent administration of mealtime insulin boluses, and sustained sensor use. These results support the potential of financial rewards for improving outcomes in youth with type 1 diabetes.