Tailoring treatment to the individual in type 2 diabetes practical guidance from the Global Partnership for Effective Diabetes Management

Good glycaemic control continues to be the most effective therapeutic manoeuvre to reduce the risk of development and/or progression of microvascular disease, and therefore remains the cornerstone of diabetes management despite recent scepticism about tight glucose control strategies. The impact on macrovascular complications is still a matter of debate, and so glycaemic control strategies should be placed in the context of multifactorial intervention to address all cardiovascular risk factors. Approaches to achieve glycaemic targets should always ensure patient safety, and results from recent landmark outcome studies support the need for appropriate individualisation of glycaemic targets and of the means to achieve these targets, with the ultimate aim to optimise outcomes and minimise adverse events, such as hypoglycaemia and marked weight gain. The primary goal of the Global Partnership for Effective Diabetes Management is the provision of practical guidance to improve patient outcomes and, in this article, we aim to support healthcare professionals in appropriately tailoring type 2 diabetes treatment to the individual. Patient groups requiring special consideration are identified, including newly diagnosed individuals with type 2 diabetes but no complications, individuals with a history of inadequate glycaemic control, those with a history of cardiovascular disease, children and individuals at risk of hypoglycaemia. Practical guidance specific to each group is provided.

Placement year academic benefit revisited:effects of demographics, prior achievement and degree programme

Investigations of whether students taking undergraduate work placements show greater academic improvement than those who do not have shown inconsistent results. In most studies, sample sizes have been relatively small and few studies have taken into account pre-existing student differences.Here data from over 6000 students at one university over six cohorts and a range of programmes are analysed. Consistent academic benefit from placement experience, regardless of ethnicity, gender, socioeconomic background and subject is shown. However the impact of demographic factors on both achievement and on the probability of taking a placement suggests that future research should take these factors into account. The role of placements in promoting employability is contextualised as a secondary benefit to the primary goal of educating the mind in the Newman (1852) tradition. Possible causes of, and further research into, the improved academic performance identified are discussed.

Role of β-adrenergic receptors in the anti-obesity and anti-diabetic effects of zinc-α2-glycoprotien (ZAG)

Objectives: The goal of the current study is to determine whether the ß-adrenoreceptor (ß-AR) plays a role in the anti-obesity and anti-diabetic effects of zinc-a2-glycoprotein (ZAG). Material and methods: This has been investigated in CHO-K1 cells transfected with the human ß1-, ß2-, ß3-AR and in ob/ob mice. Cyclic AMP assays were carried out along with binding studies. Ob/ob mice were treated with ZAG and glucose transportation and insulin were examined in the presence or absence of propranolol. Results: ZAG bound to the ß3-AR with higher affinity (Kd 46±1nM) than the ß2-AR (Kd 71±3nM) while there was no binding to the ß1-AR, and this correlated with the increases in cyclic AMP in CHO-K1 cells transfected with the various ß-AR and treated with ZAG. Treatment of ob/ob mice with ZAG increased protein expression of ß3-AR in gastrocnemius muscle, and in white and brown adipose tissues, but had no effect on expression of ß1- and ß2-AR. A reduction of body weight was seen and urinary glucose excretion, increase in body temperature, reduction in maximal plasma glucose and insulin levels in the oral glucose tolerance test, and stimulation of glucose transport into skeletal muscle and adipose tissue, were completely attenuated by the non-specific ß-AR antagonist propranolol. Conclusion: The results suggest that the effects of ZAG on body weight and insulin sensitivity in ob/ob mice are manifested through a ß-3AR, or possibly a ß2-AR.

Az európai uniós támogatások hatékonysága és hatásossága közötti különbség a ROP 1.2 intézkedésnél (The difference between the efficiency and effectiveness of using the EU-subsidies at Regional Operational Program)

A szerző cikkében megpróbál rávilágítani annak fontosságára, hogy az Európai Unióból érkező fejlesztési támogatások hasznosulása és a támogatási rendszer hatékonysága között jelentős különbség van. Ha nem tudjuk hatékonyan és hatásosan felhasználni az Unióból érkező pénzügyi eszközöket, akkor a cél: a kohézió, a konvergencia az Európai Unió régi tagállamainak fejlettségi szintjéhez, jólétéhez még nehezebben és lassabban érhető el. Az uniós támogatások hatékonysága alapvetően a rendelkezésre álló pénz lekötésének, lehívásának arányából, illetve a lekötött, lehívott és esetleg visszafizetett összeg arányából állapítható meg (kvantitatív megközelítés). A támogatások felhasználásának hatékonyságánál bonyolultabb, jóval összetettebb megközelítést igényel a hatásosság fogalma. A felhasználás hatásosságát a projektszinten a támogatás hatására megtermelt hozzáadott értékkel, programszinten a GDP hozzáadott növekedéssel lehet kifejezni. A cikk alapvetően a ROP 1.2 "Turisztikai fogadóképesség javítása" pályázati kiírás nyertes projektjeinél végzett kutatás eredményein keresztül kívánja szemléltetni a projektszintű vagy mikro hatásosság fontosságára (kvalitatív megközelítés). _________ The author tries to highlight the importance the difference between the efficiency and effectiveness of using the EU-subsidies. If Hungary cannot use the financial means of the EU efficiently and effectively, than the goal: cohesion and convergence to the level of the old, developed countries of the EU will be much harder and slowly. The efficiency of the EU-subsidies can be measured by the ratio of the amount of money obliged and the amount of money spent, and by the amount of money withdrawn by the Commission, which is actually lost (quantitative approach). The effectiveness of EU-subsidies needs a much more complicated and complex approach, than the efficiency. The effectiveness of usage on project level can be measured by the "added value" of the project, on program level by the added GDP growth or employment. The article is analysing basically the results of a survey made among the winner project of the application ROP 1.2 (Regional Operational Program 1.2) Improving the capacity for tourism (project level or micro effectiveness – qualitative approach).

Self -management factors, influences, and conditions for type 2 diabetes among Black ethnic groups in Miami, Florida and Abidjan, Cote d'Ivoire

The Dahlgren and Whitehead ecological theory provides the framework for a cross-sectional design to compare socio-demographic characteristics, living and working conditions, and lifestyle daily habits as well as cultural and ecological factors among six diabetic multiethnic Black groups in Miami and Abidjan. Approximately 180 Black Americans (African-, Caribbean-, and Haitian-) and 180 Black Africans (Akan, Malinke, and Krou) aged 20 years and older were surveyed. During the preliminary of this study participants' attitudes and behaviors were qualitatively assessed (N=60) and a tool was developed to describe, in the main study (N=360), differences in participants' strength of commitment to diabetes lifestyle self-management. Despite similarities found in terms of age and gender, statistically significant differences were also found within and among groups in terms of living and working conditions, education level, and religion. African American groups were more likely to participate in more diabetes classes than Haitian Americans and Caribbean Americans. However, African Americans were less likely to adhere to daily dietary and weight control regimens. Although, Black African groups reported limited access to equipment, facilities, and financial support they were more likely to follow dietary and weight control recommendations than Black American groups. Overall, African American participants showed the poorest attitudes towards recommended foods, Caribbean American respondents reported the best attitudes and behaviors towards weight control regimens, and the Malinke group had significantly more strength of commitment to successful weight control. Furthermore, Black African groups had significantly more strength of commitment to successful dietary adherence and significantly less support for weight control than Black American groups. ^ Significant differences found within Black groups suggest that understanding each patient's conditions may help healthcare professionals in initiating individualized appropriate counseling before goal setting, and in developing culturally relevant type 2 diabetes management programs. Moreover, significant differences exist in strength of commitment to lifestyle adherence among Black groups in Miami and Abidjan. Cultural, socio-demographic factors and self-management habits may explain differences in participants' outcomes. At the policy level, Black groups should not be approached as a homogenous group and assessment of the vulnerability of each ethnic group may be necessary in the decision-making process.^

Synthesis and Properties of a Series of 1,1,n,n-Tetramethyl[n](2,11)teropyrenophanes

The work described in this thesis revolves around the 1,1,n,ntetramethyl[n](2,11)teropyrenophanes, which are a series of [n]cyclophanes with a severely bent, board-shaped polynuclear aromatic hydrocarbons (PAH). The thesis is divided into seven Chapters. The first Chapter conatins an overview of the seminal work on [n]cyclophanes of the first two members of the “capped rylene” series of PAHs: benzene and pyrene. Three different general strategies for the synthesis of [n]cyclophanes are discussed and this leads in to a discussion of some slected syntheses of [n]paracyclopahnes and [n](2,7)pyrenophanes. The chemical, structural, spectroscopic and photophysical properties of these benzene and pyrene-derived cyclophanes are discussed with emphasis on the changes that occur with changes in the structure of the aromatic system. Chapter 1 concludes with a brief introduction to [n]cyclophanes of the fourth member of the capped rylene series of PAHs: teropyrene. The focus of the work described in Chapter 2 is the synthesis of of 1,1,n,ntetramethyl[n](2,11)teropyrenophane (n = 6 and 7) using a double-McMurry strategy. While the synthesis 1,1,7,7-tetramethyl[7](2,11)teropyrenophane was successful, the synthesis of the lower homologue 1,1,6,6-tetramethyl[6](2,11)teropyrenophane was not. The conformational behaviour of [n.2]pyrenophanes was also studied by 1H NMR spectroscopy and this provided a conformation-based rationale for the failure of the synthesis of 1,1,6,6-tetramethyl[6](2,11)teropyrenophane. Chapter 3 contains details of the synthesis of 1,1,n,n-tetramethyl[n](2,11)teropyrenophanes (n = 7-9) using a Wurtz / McMurry strategy, which proved to be more general than the double McMurry strategy. The three teropyrenophanes were obtained in ca. 10 milligram quantities. Trends in the spectroscopic properties that accompany changes in the structure of the teropyrene system are discussed. A violation of Kasha’s rule was observed when the teropyrenophanes were irradiated at 260 nm. The work described in the fourth Chapter concentrates on the development of gram-scale syntheses of 1,1,n,n-tetramethyl[n](2,11)teropyrenophanes (n = 7–10) using the Wurtz / McMurry strategy. Several major modifications to the orginal synthetic pathway had to be made to enable the first several steps to be performed comfortably on tens of grams of material. Solubility problems severely limited the amount of material that could be produced at a late stage of the synthetic pathways leading to the evennumbered members of the series (n = 8, 10). Ultimately, only 1,1,9,9- tetramethyl[9](2,11)teropyrenophane was synthesized on a multi-gram scale. In the final step in the synthesis, a valence isomerization / dehydrogenation (VID) reaction, the teropyrenophane was observed to become unstable under the conditions of its formation at n = 8. The synthesis of 1,1,10,10-tetramethyl[10](2,11)teropyrenophane was achieved for the first time, but only on a few hundred milligram scale. In Chapter 5, the results of an investigation of the electrophilic aromatic bromination of the 1,1,n,n-tetramethyl[n](2,11)teropyrenophanes (n = 7–10) are presented. Being the most abundant cyclophane, most of the work was performed on 1,1,9,9-tetramethyl[9](2,11)teropyrenophane. Reaction of this compound with varying amounts of of bromine revealed that bromination occurs most rapidly at the symmetryrelated 4, 9, 13 and 18 positions (teropyrene numbering) and that the 4,9,13,18- tetrabromide could be formed exclusively. Subsequent bromination occurs selectively on the symmetry-related 6, 7, 15 and 16 positions (teropyrene numbering), but considerably more slowly. Only mixtures of penta-, hexa-, hepta and octabromides could be formed. Bromination reactions of the higher and lower homologues (n = 7, 8 and 10) revealed that the reactivity of the teropyrene system increased with the degree of bend. Crystal structures of some tetra-, hexa-, hepta- and octa-brominated products were obtained. The goal of the work described in Chapter 6 is to use 1,1,9,9- tetramethyl[9](2,11)teropyrenophane as a starting material for the synthesis of warped nanographenophanes. A bromination, Suzuki-Miyaura, cyclodehydrogenation sequence was unsuccessful, as was a C–H arylation / cyclodehydrogenation approach. Itami’s recently-developed K-region-selective annulative -extension (APEX) reaction proved to be successful, affording a giant [n]cyclophane with a C84 PAH. Attempted bay-region Diels-Alder reactions and some cursory host-guest chemistry of teropyrenophanes are also discussed. In Chapter 7 a synthetic approach toward a planar model compound, 2,11-di-tbutylteropyrene, is described. The synthesis could not be completed owing to solubility problems at the end of the synthetic pathway.

Polonium-210 and Lead-210 activities measured on 17 water bottle profiles and 50 surface water samples during POLARSTERN cruise ARK-XXII/2

Polonium-210 and Lead-210 have been measured in the water column and on suspended particulate matter during the POLARSTERN cruise ARK-XXII/2. The data have been submitted to Pangaea following a Polonium-Lead intercalibration exercise organized by GEOTRACES, where the AWI lab results range within the data standard deviation from 10 participating labs. Polonium-210 and Lead-210 in the ocean can be used to identify the sources and sinks of suspended matter. In seawater, Polonium-210 (210Po) and Lead-210 (210Pb) are produced by stepwise radioactive decay of Uranium-238. 210Po (138 days half life) and 210Pb (22.3 years half life) have high affinities for suspended particles. Those radionuclides are present in dissolved form and adsorbed onto particles. Following adsorption onto particle surfaces, 210Po especially is transported into the interior of cells where it bonds to proteins. In this way, 210Po also accumulates in the food chain. 210Po is therefore considered to be a good tracer for POC, and traces particle export over a timescale of month. 210Pb (22.3 years half life) adsorbs preferably onto structural components of cells, biogenic silica and lithogenic particles, and is therefore a better tracer more rapidly sinking matter. Our goal during ARK XXII/2 was to trace pathways of particulate and dissolved matter leaving the Siberian Shelf. The pathways of particulate and dissolved matter will be followed by the combined use of 210Po and 234Th as a tracer pair (and perhaps 210Pb) for particle flux (Cai, P.; Rutgers van der Loeff, MM (2008) doi:10.1594/PANGAEA.708354). This information gathered from the water column will be complemented with the results of the 210Po-210Pb study in sea ice (Camara-Mor, P, Instituto de Ciencias del Mar-SCIC, Barcelona, Spain) to provide a more thorough picture of particle transport from the shelf to the open sea and from surface to depth.

Dual modulation of cell survival and cell death by beta(2)-adrenergic signaling in adult mouse cardiac myocytes.

The goal of this study was to determine whether beta(1)-adrenergic receptor (AR) and beta(2)-AR differ in regulating cardiomyocyte survival and apoptosis and, if so, to explore underlying mechanisms. One potential mechanism is that cardiac beta(2)-AR can activate both G(s) and G(i) proteins, whereas cardiac beta(1)-AR couples only to G(s). To avoid complicated crosstalk between beta-AR subtypes, we expressed beta(1)-AR or beta(2)-AR individually in adult beta(1)/beta(2)-AR double knockout mouse cardiac myocytes by using adenoviral gene transfer. Stimulation of beta(1)-AR, but not beta(2)-AR, markedly induced myocyte apoptosis, as indicated by increased terminal deoxynucleotidyltransferase-mediated UTP end labeling or Hoechst staining positive cells and DNA fragmentation. In contrast, beta(2)-AR (but not beta(1)-AR) stimulation elevated the activity of Akt, a powerful survival signal; this effect was fully abolished by inhibiting G(i), G(beta gamma), or phosphoinositide 3 kinase (PI3K) with pertussis toxin, beta ARK-ct (a peptide inhibitor of G(beta gamma)), or LY294002, respectively. This indicates that beta(2)-AR activates Akt via a G(i)-G(beta gamma)-PI3K pathway. More importantly, inhibition of the G(i)-G(beta gamma)-PI3K-Akt pathway converts beta(2)-AR signaling from survival to apoptotic. Thus, stimulation of a single class of receptors, beta(2)-ARs, elicits concurrent apoptotic and survival signals in cardiac myocytes. The survival effect appears to predominate and is mediated by the G(i)-G(beta gamma)-PI3K-Akt signaling pathway.

Synthesis of a PbTx-2 photoaffinity and fluorescent probe and an alternative synthetic route to photoaffinity probes

A natural phenomenon characterized by dense aggregations of unicellular photosynthetic marine organisms has been termed colloquially as red tides because of the vivid discoloration of the water. The dinoflagellate Karenia brevis is the cause of the Florida red tide bloom. K. brevis produces the brevetoxins, a potent suite of neurotoxins responsible for substantial amounts of marine mammal and fish mortalities. When consumed by humans, the toxin causes Neurotoxic Shellfish Poisoning (NSP). The native function of brevetoxin within the organism has remained mysterious since its discovery. There is a need to identify factors which contribute to and regulate toxin production within K. brevis. These toxins are produced and retained within the cell implicating a significant cellular role for their presence. Localization of brevetoxin and identification of a native receptor may provide insight into its native role as well as other polyether ladder type toxins such as the ciguatoxins, maitotoxins, and yessotoxins. In higher organisms these polyether ladder molecules bind to transmembrane proteins with high affinity. We anticipated the native brevetoxin receptor would also be a transmembrane protein. Photoaffinity labeling has become increasingly popular for identifying ligand receptors. By attaching ligands to these photophors, one is able to activate the molecule after the ligand binds to its receptor to obtain a permanent linkage between the two. Subsequent purification provides the protein with the ligand directly attached. A molecule that is capable of fluorescence is a fluorophore, which upon excitation is capable of re-emitting light. Fluorescent labeling uses fluorophores by attaching them covalently to biologically active compounds. The synthesis of a brevetoxin photoaffinity probe and its application in identifying a native brevetoxin receptor will be described. The preparation of a fluorescent derivative of brevetoxin will be described and its use in localizing the toxin to an organelle within K. brevis. In addition, the general utility of a synthesized photoaffinity label with other toxins having similar functionality will be described. An alternative synthetic approach to a general photoaffinity label will also be discussed whose goal was to accelerate the preparation and improve the overall synthetic yields of a multifunctional label.

Structural and Functional Characterization of the Human Tribbles Homologue 2 Pseudokinase

The Tribbles Homologues are a family of three eukaryotic pseudokinases (Trb1, Trb2, Trb3) that act as allosteric inhibitors and regulatory scaffold sites in pathways governing adipogenesis, cell proliferation and insulin signaling. The Tribbles Homologues have the same overall tertiary structure of the eukaryotic protein kinase domain, but lack multiple residues necessary to catalysis in the nucleotide-binding P-loop and the Mg2+-coordinating DFG motif. Trb1 has been shown conclusively to be incapable of binding ATP, whereas a recent study presents evidence that Trb2 autophosphorylates independently of Mg2+ in vitro. This finding is surprising given the high degree of sequence similarity between the two proteins (71%), and suggests unique nucleotide binding and phosphotransfer mechanisms. The goal of this project was to investigate whether Trb2 possesses kinase activity or not and determine its structural basis. A method for the high-yield recombinant expression and purification of stable Trb2 was developed. Trb2 nucleotide binding and autophosphorylation could not be detected across multiple experimental approaches, including thermal shift assays, MANT-ATP fluorescence, radiolabeled phosphate incorporation, and nonspecific ATPase activity assays. Further characterization also revealed that Trb2 forms homomultimers with possible functional consequences, and extensive crystallization screening has yielded multiple promising conditions that could produce diffraction-quality crystals with further optimization. This project explores the difficulties in functionally characterizing putatively active pseudokinases, and proposes a structural basis for the conserved pseudokinase features of the Tribbles homologues.

Development and Evaluation of a Computer-Based, Self-Management Tool for People Recently Diagnosed with Type 2 Diabetes

Aim. The purpose of this study was to develop and evaluate a computer-based, dietary, and physical activity self-management program for people recently diagnosed with type 2 diabetes. 
Methods. The computer-based program was developed in conjunction with the target group and evaluated in a 12-week randomised controlled trial (RCT). Participants were randomised to the intervention (computer-program) or control group (usual care). Primary outcomes were diabetes knowledge and goal setting (ADKnowl questionnaire, Diabetes Obstacles Questionnaire (DOQ)) measured at baseline and week 12. User feedback on the program was obtained via a questionnaire and focus groups. Results. Seventy participants completed the 12-week RCT (32 intervention, 38 control, mean age 59 (SD) years). After completion there was a significant between-group difference in the “knowledge and beliefs scale” of the DOQ. Two-thirds of the intervention group rated the program as either good or very good, 92% would recommend the program to others, and 96% agreed that the information within the program was clear and easy to understand. 
Conclusions. The computer-program resulted in a small but statistically significant improvement in diet-related knowledge and user satisfaction was high. With some further development, this computer-based educational tool may be a useful adjunct to diabetes self-management.

Development of N N SMRT for N a power of 2 and its Applications in Image Enhancement

Digital Image Processing is a rapidly evolving eld with growing applications in Science and Engineering. It involves changing the nature of an image in order to either improve its pictorial information for human interpretation or render it more suitable for autonomous machine perception. One of the major areas of image processing for human vision applications is image enhancement. The principal goal of image enhancement is to improve visual quality of an image, typically by taking advantage of the response of human visual system. Image enhancement methods are carried out usually in the pixel domain. Transform domain methods can often provide another way to interpret and understand image contents. A suitable transform, thus selected, should have less computational complexity. Sequency ordered arrangement of unique MRT (Mapped Real Transform) coe cients can give rise to an integer-to-integer transform, named Sequency based unique MRT (SMRT), suitable for image processing applications. The development of the SMRT from UMRT (Unique MRT), forward & inverse SMRT algorithms and the basis functions are introduced. A few properties of the SMRT are explored and its scope in lossless text compression is presented.

Régulation épigénétique de la défense antioxydante et de l'Angiopoietin-like 2 dans le contexte du vieillissement et des maladies cardiovasculaires

Suite à l’exposition à des facteurs de risque incluant la malnutrition, la dyslipidémie, la sédentarité et les désordres métaboliques, les maladies cardiovasculaires (MCV) sont caractérisées par un état pro-oxydant et pro-inflammatoire, et une dérégulation de l’expression de divers facteurs responsables de l’homéostasie de l’environnement rédox et inflammatoire. L’implication d’enzymes antioxydantes telles que les superoxyde dismutases (SOD) et les glutathion peroxydases (Gpx), ainsi que la contribution de médiateurs pro-inflammatoires tels que l’angiopoietin-like 2 (Angptl2) ont été rapportées dans le cadre des MCV. Toutefois, les mécanismes moléculaires sensibles aux facteurs de risque et menant au développement des MCV sont peu connus. L’épigénétique est un mécanisme de régulation de l’expression génique sensible aux stimuli extracellulaires et pourrait donc contribuer au développement des MCV. La méthylation de l’ADN est un des mécanismes épigénétiques pouvant varier tant de manière gène-spécifique qu’à l’échelle génomique, et la conséquence de tels changements sur l’expression des gènes ciblés dépend du site de méthylation. Puisqu’il a été démontré que des variations au niveau de la méthylation de l’ADN peuvent être associées à divers contextes pathologiques incluant les MCV, le but de nos travaux était d’étudier le lien entre la méthylation de gènes antioxydants et pro-inflammatoires avec leurs répercussions fonctionnelles biologiques en présence de facteurs de risques associés aux MCV, tels que le vieillissement, la dyslipidémie et la sédentarité. Dans la première étude, nous avons observé que dans l’artère fémorale de souris vieillissantes, la méthylation au niveau du promoteur du gène Sod2, codant pour l’enzyme antioxydante superoxyde dismutase de type 2 (SOD2 ou MnSOD), diminue avec l’âge. Ceci serait associé à l’induction de l’expression de MnSOD, renforçant ainsi la défense antioxydante endogène. Le vieillissement étant associé à une accumulation de la production de radicaux libres, nous avons étudié la vasodilatation dépendante de l’endothélium qui est sensible au stress oxydant. Nous avons observé que la capacité vasodilatatrice globale a été maintenue chez les souris âgées, aux dépens d’une diminution des facteurs hyperpolarisants dérivés de l’endothélium (EDHF) et d’une contribution accentuée de la voie du monoxyde d’azote (NO). Nous avons ensuite utilisé deux approches visant à réduire les niveaux de stress oxydant in vivo, soit la supplémentation avec un antioxydant, la catéchine, et l’exposition chronique à de l’exercice physique volontaire. Ces interventions ont permis de prévenir à la fois les changements au niveau de la fonction endothéliale et de l’hypométhylation de Sod2. Cette première étude démontre donc la sensibilité de la méthylation de l’ADN à l’environnement rédox. Dans la deuxième étude, nous avons démontré une régulation de l’expression de l’enzyme antioxydante glutathion peroxydase 1 (Gpx1) en lien avec la méthylation de son gène codant, Gpx1, dans un contexte de dyslipidémie sévère. Nos résultats démontrent que dans le muscle squelettique de souris transgéniques sévèrement dyslipidémiques (LDLr-/-; hApoB+/+), Gpx1 est hyperméthylé, ce qui diminue l’expression de Gpx1 et affaiblit la défense antioxydante endogène. Chez ces souris, l’exercice physique chronique a permis d’augmenter l’expression de Gpx1 en lien avec une hypométhylation transitoire de son gène. Cette étude démontre que le stress oxydant associé à la dyslipidémie sévère altère les mécanismes de défense antioxydante, en partie via un mécanisme épigénétique. De plus, on observe également que l’exercice physique permet de renverser ces effets et peut induire des changements épigénétiques, mais de manière transitoire. La troisième étude avait pour but d’étudier la régulation de l’Angptl2, une protéine circulante pro-inflammatoire, dans le contexte des MCV. Nous avons observé que chez des patients coronariens, la concentration circulante d’Angptl2 est significativement plus élevée que chez des sujets sains et ce, en lien avec une hypométhylation de son gène, ANGPTL2, mesurée dans les leucocytes circulants. Nous sommes les premiers à démontrer qu’en réponse à l’environnement pro-inflammatoire associé à une MCV, l’expression de l’Angptl2 est stimulée par un mécanisme épigénétique. Nos études ont permis d’identifier des nouvelles régions régulatrices différentiellement méthylées situées dans les gènes impliqués dans la défense antioxydante, soit Sod2 en lien avec le vieillissement et Gpx1 en lien avec la dyslipidémie et l’exercice. Nous avons également démontré un mécanisme de régulation de l’Angptl2 dépendant de la méthylation d’ANGPTL2 et ce, pour la première fois dans un contexte de MCV. Ces observations illustrent la nature dynamique de la régulation épigénétique par la méthylation de l’ADN en réponse aux stimuli environnementaux. Nos études contribuent ainsi à la compréhension et l’identification de mécanismes moléculaires impliqués dans le développement du phénotype pathologique suite à l’exposition aux facteurs de risque, ce qui ouvre la voie à de nouvelles approches thérapeutiques.

Caractérisation et optimisation d'un détecteur à scintillation à 2 points

Ce projet de recherche s’inscrit dans le domaine de la dosimétrie à scintillation en radiothérapie, plus précisément en curiethérapie à haut débit de dose (HDR). Lors de ce type de traitement, la dose est délivrée localement, ce qui implique de hauts gradients de dose autour de la source. Le but de ce travail est d’obtenir un détecteur mesurant la dose en 2 points distincts et optimisé pour la mesure de dose en curiethérapie HDR. Pour ce faire, le projet de recherche est séparé en deux études : la caractérisation spectrale du détecteur à 2-points et la caractérisation du système de photodétecteur menant à la mesure de la dose. D’abord, la chaine optique d’un détecteur à scintillation à 2-points est caractérisée à l’aide d’un spectromètre afin de déterminer les composantes scintillantes optimales. Cette étude permet de construire quelques détecteurs à partir des composantes choisies pour ensuite les tester avec le système de photodétecteur multi-point. Le système de photodétecteur est aussi caractérisé de façon à évaluer les limites de sensibilité pour le détecteur 2-points choisi précédemment. L’objectif final est de pouvoir mesurer le débit de dose avec précision et justesse aux deux points de mesure du détecteur multi-point lors d’un traitement de curiethérapie HDR.

A docência enquanto paixão:construção da profissionalidade no 1º e 2º ciclo do ensino básico

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