Indiana University-Purdue University Indianapolis (IUPUI) / Our laboratory has previously identified the clock gene D-box Binding Protein (DBP) as a candidate gene for bipolar disorder and alcoholism using a Convergent Functional Genomics (CFG) approach. In subsequent work, we established mice with a homozygous deletion of DBP as a stress-reactive genetic animal model of bipolar disorder and co-morbid alcoholism. In the present study, we found that the omega-3 fatty acid, DHA, may have mood stabilizing capabilities in stressed DBP knockout mice, and reduces alcohol consumption in these mice as well as in the alcohol preferring (P) rats. Given their potential health benefits and their relative lack of negative side-effects, omega-3 fatty acids may become an important supplement for bipolar patients and co-morbid alcoholics, a potential that warrants continued research.

Purpose: To 1) critically appraise available randomized controlled trials (RTCs) addressing the efficacy of long-chain ω-3 fatty acids as a secondary prevention agent of hypertriglyceridemia, and 2) make recommendations for clinical practice. Data Sources: All RCTs identified from several databases from 1993-2003 were reviewed by two independent reviewers who extracted data from each study and used the previously tested Boyack and Lookinland Methodological Quality Index (MQI) to determine study quality. Results: Ten studies reported long-chain ω-3 fatty acids to be effective in the treatment of hypertriglyceridemia. The average decrease in triglycerides (TG) was 29%, total cholesterol (TC) 11.6%, very low density lipoprotein (VLDL) 30.2%, and low-density lipoprotein (LDL) 32.5%. One study found LDLs to increase by 25%. The average increase in high-density lipoprotein (HDL) was 10%. The overall average MQI score was 36% (26%-54%). Many of the RCTs had serious shortcomings including short duration, lack of a power analysis, no intention to treat analysis, no report of blind assessment of outcome, and lack of dietary control as a confounding variable. Conclusions/Implications: Overall study methodology was weak. Although the evidence supporting the use of long-chain ω-3 fatty acids in the secondary prevention of hypertriglyceridemia is reasonably strong, until there are larger RCTs of stronger methodological quality, it is not recommended to treat hypertriglyceridemia with ω-3 fatty acid supplementation in lieu of lipid lowering medications.

Federal and state policies affecting higher education, like the Morrill Land Grant Act of 1832, Brown vs. Board of Education, and Higher Education Act of 1965 have posited change regarding the proliferation of diversity and expansion of access (Thelin, 2011). I analyzed BOT policies for enrollment and conducted a socio-diagnostic CDA on the implementation of admission policy to understand the impact of the policies’ implementation. I focused on 1) exploring how open enrollment (OE) policies were constructed, 2) how institutions adopt and interpret these policies, and 3) how individuals at the institution enact these policies, by conducting a discourse-historical analysis (DHA). Open enrollment has been extensively studied at junior colleges. However, the impact of open admissions (OA) at 4-year institutions has not been intensely engaged despite its use at these types of institutions. This has left professionals to draw implications for practice from universities and colleges that are different than the ones in which they work. There are conditions that could inhibit the effectiveness of education policy implementation to include: “a lack of focus on the implementation processes when defining policies at the system level; a lack of recognition that the core of change processes require engaging people; and the fact that implementation processes need to be revised to adapt to new complex governance systems” (Viennet & Pont, 2017, p. 6). I conducted a case study investigation of open enrollment policy at a 4-year public university to understand its implementation and impact on the student experience. I used discourse-historical analysis to guide my analysis of the data. Implications were creation of a student profile, resource support matrix, and rethink of policy implementation.

Students diagnosed with long-term mental health conditions have been the focus of policy development for over a decade. Student mental health is on the increase and universities are legally obliged to make reasonable adjustments for disabled students. Therefore it is crucial that nursing and midwifery education provides an inclusive learning environment, while maintaining fitness to practice standards. The focus of this study was to explore how discourses of mental health, reasonable adjustments and fitness standards influence nursing and midwifery education for students with a mental health condition. Principles of Wodak’s (2001) critical discourse analysis approach, which gives prominence to dominant discourses, their justifications and persuasive nature was utilised. Ten key written texts and 23 semi-structured interviews with students, lecturers and clinical mentors were conducted to acquire the constructions of mental health, reasonable adjustments and fitness requirements. The findings show that the dominant discourses attributed to students experiencing mental ill health were around medicine, difference and blame, all of which reinforced mental health stigma. In addition, mental health discourses within both verbal and written texts were not underpinned by disability discourses, allowing the exclusion of students who disclose mental ill health from accessing reasonable adjustments. In conclusion, students considered to have a mental health label faced discriminatory barriers and legislative and regulatory requirements of equality were not implemented.

Yes / Abstract Objective Omega-3 polyunsaturated fatty acids (PUFAs) have anticolorectal cancer (CRC) activity. The intestinal microbiota has been implicated in colorectal carcinogenesis. Dietary omega-3 PUFAs alter the mouse intestinal microbiome compatible with antineoplastic activity. Therefore, we investigated the effect of omega-3 PUFA supplements on the faecal microbiome in middle-aged, healthy volunteers (n=22). Design A randomised, open-label, cross-over trial of 8 weeks’ treatment with 4 g mixed eicosapentaenoic acid/docosahexaenoic acid in two formulations (soft-gel capsules and Smartfish drinks), separated by a 12-week ‘washout’ period. Faecal samples were collected at five time-points for microbiome analysis by 16S ribosomal RNA PCR and Illumina MiSeq sequencing. Red blood cell (RBC) fatty acid analysis was performed by liquid chromatography tandem mass spectrometry. Results Both omega-3 PUFA formulations induced similar changes in RBC fatty acid content, except that drinks were associated with a larger, and more prolonged, decrease in omega-6 PUFA arachidonic acid than the capsule intervention (p=0.02). There were no significant changes in α or β diversity, or phyla composition, associated with omega-3 PUFA supplementation. However, a reversible increased abundance of several genera, including Bifidobacterium, Roseburia and Lactobacillus was observed with one or both omega-3 PUFA interventions. Microbiome changes did not correlate with RBC omega-3 PUFA incorporation or development of omega-3 PUFA-induced diarrhoea. There were no treatment order effects. Conclusion Omega-3 PUFA supplementation induces a reversible increase in several short-chain fatty acid-producing bacteria, independently of the method of administration. There is no simple relationship between the intestinal microbiome and systemic omega-3 PUFA exposure. / NIHR/EME Yorkshire Cancer Research (YCR)

The year 2024 started with newspapers filled with articles on farmers taking over European cities. In Germany, the farmers protested the recently announced tax break reduction on agricultural diesel. The protests were quickly instrumentalized by various political actors, which made them highly controversial. This thesis explores how two actors, the German radical right AfD and the center-right CDU, discursively construct climate change within the debates surrounding the farmers’ protests. The focus lies on their use of populism as a strategic communication tool and legitimation strategies that politicize climate change. As such, climate change and environmental discourses are critically reviewed and contextualized, and theories on populism and politicization are presented. The thesis applies a discourse-historical approach (DHA) based on the analytical tools of nomination, predication, and legitimation. The findings conclude that discourses of climate policy conservatism, green patriotism, and climate elitism are applied to re-politicize climate change according to the right-wing agenda. As expected, the AfD mainly applied green patriotism, whereas the CDU applied climate policy conservatism. Both also relied on a newly identified discourse of climate elitism, highlighting the protest dynamics.

Introdução - Os hábitos alimentares e os nutrientes da via metabólica do folato e homocisteína possuem grande importância na manutenção da saúde. Objetivo - Investigar a relação entre padrões alimentares (PAs) e os nutrientes envolvidos nessa via metabólica, com medidas antropométricas do recém-nascido, duração da infecção por HPV em homens e concentrações de homocisteína (Hcy) em adultos. Métodos - Foram utilizados dados dos estudos de coorte ProcriAr (Influência dos fatores nutricionais e poluentes atmosféricos urbanos na saúde pulmonar de crianças: um estudo de coorte com gestantes da zona oeste do município de São Paulo, n=299); e HIM (História natural da infecção por HPV em homens, n=1.194); e do estudo transversal ISA-Capital 2008 (Inquérito de saúde do estado de São Paulo, n=281). Os padrões alimentares foram derivados por análise fatorial por componentes principais nos estudos ProcriAr e ISA-Capital 2008 e utilizando reduced rank regression (RRR) no estudo HIM. Modelos multivariados de regressão de Poisson e lineares foram utilizados nos estudos ProcriAr e HIM para identificar a relação entre PAs e medidas antropométricas do recém-nascido e duração da infecção por HPV em homens, respectivamente. Utilizando modelo de equação estrutural, investigou-se a relação entre PAs, concentrações bioquímicas de folato, vitamina B12 e ácido docosahexaenoico (DHA) e concentrações de homocisteína em adultos do estudo ISA-Capital, considerando polimorfismo da enzima metilenotetrahidrofolato redutase (MTHFR 677C>T). Os três estudos utilizaram questionário de frequência alimentar para avaliação do consumo alimentar. Resultados - No estudo ProcriAr, a maior adesão materna ao PA \"Snacks, sanduíches, doces e refrigerantes\", rico em energia, gordura, e folato sintético, esteve diretamente associada a ter um filho pequeno ao nascer (peso e/ou comprimento ao nascer, ajustado pela idade gestacional, abaixo do percentil 10 - INTERGOWTH-21st) (RR: 2,01; IC 95%: 1.13-3.57). No estudo HIM, homens com maior adesão ao \"PA3\" tiveram, em média, um aumento de 1,15 (IC95% 0,09-2,21) à 1,18 (IC95% 0,11-2,24) meses na duração da infecção por HPV. O \"PA3\" esteve positivamente correlacionado com vitamina B6 (r = 0,59), vitamina B12 (0,27) e DFE (0,07) e negativamente correlacionado com DHA (-0,37). No estudo ISA-Capital o PA \"Prudente\" esteve inversamente associado à concentração de Hcy (β = -0,12). O DHA esteve diretamente associado ao PA \"Prudente\"; composto por verduras e legumes, peixe, frutas, frango, suco natural e batata/mandioca/polenta (cozida ou assada). Conclusões - Os PAs estão associados às medidas antropométricas do recém-nascido, à duração da infecção por HPV em homens e às concentrações de homocisteína em adultos. Estes resultados reforçam a importância de estudos sobre alimentação e nutrição que considerem não somente nutrientes, mas principalmente o consumo de alimentos e suas combinações, servindo como base para a elaboração de estratégias e políticas públicas de promoção à saúde. / Introduction - The dietary habits and nutrients involved in one-carbon metabolism are of great importance in health. Objective - To investigate the relationship between dietary patterns (DP) and the nutrients involved in this metabolism, with newborn\'s anthropometric measurements, duration of HPV infection in men, and homocysteine (Hcy) levels in adults. Methods - Data from the cohort studies ProcriAr (Influence of nutritional factors and urban air pollutants on the pulmonary health of children: a cohort study with pregnant women from the western region of the city of São Paulo, n=299); and HIM (Natural history of HPV infection in men, n=1,194); and the cross-sectional study ISA-Capital 2008 (São Paulo State Health Survey, n=281) were used. The DP were estimated using factor analysis with principal component\'s estimation in ProcriAr and ISA-Capital 2008 studies and using reduced rank regression (RRR) in HIM study. Multivariate Poisson and linear regression models were used in the ProcriAr and HIM studies to identify the relationship between DP and newborn\'s anthropometric measurements and duration of HPV infection in men, respectively. Using a structural equation model, the relationship between DP, biochemical levels of folate, vitamin B12 and docosahexaenoic acid (DHA) and homocysteine levels was investigated in adults from the ISA-Capital 2008 study, considering the polymorphism of the enzyme methylenetetrahydrofolate reductase (MTHFR 677C>T). The three studies used a food frequency questionnaire to evaluate dietary intake. Results - In the ProcriAr study, the higher maternal adherence to the \"Snacks, sandwiches, sweets and soft drinks\" DP, which is a DP rich in energy, fat, and synthetic folate, was directly associated with having a child small at birth (weight and/or birth length by gestational age and sex below the 10th percentile - INTERGOWTH-21st) (RR: 2.01, 95% CI: 1.13-3.57). In the HIM study, men with higher adherence to \"DP3\" had, on average, an increase from 1.15 (95% CI 0.09-2.21) to 1.18 (95% CI 0.11-2.24) months in the duration of HPV infection. \"DP3\" was positively correlated with vitamin B6 (r = 0.59), vitamin B12 (0.27) and DFE (0.07) and negatively correlated with DHA (-0.37). In the ISA-Capital study, the \"Prudent\" DP was inversely associated with Hcy levels (β = -0.12). DHA was directly associated with \"Prudent\" DP; composed of vegetables, fish, fruits, chicken, natural juice and potato/cassava/polenta (cooked or roasted). Conclusions - Dietary patterns are associated with newborn\'s anthropometric measurements, duration of HPV infection in men, and Hcy levels in adults. These results reinforce the importance of studies on food and nutrition that consider not only nutrients, but mainly the consumption of foods and their combinations, serving as a basis for the elaboration of public health promotion strategies and policies.

La malnutrition liée au vieillissement est souvent accompagnée de nombreux dérèglements et dysfonctionnements métaboliques, notamment la perturbation de l'homéostasie énergétique (installation de l’insulinorésistance), la fragilité, la diminution de la masse musculaire et les troubles de la réponse immunitaire. Ainsi, la manipulation nutritionnelle, au cours du vieillissement, est considérée comme l'une des solutions possible pour prévenir et traiter ces troubles. Parmi les substances nutritives qui ont été largement étudiées, la composition en protéines (acides aminés), la qualité des lipides (AGPI n-3) et les micronutriments (vitamine D).L’objectif de cette thèse consiste à déterminer l’impact de la dénutrition et d’évaluer le potentiel d'une des formules de réalimentation contenant un mélange à haute teneur en protéines solubles du lait, associées à de la matière grasse laitière, enrichie en acides gras polyinsaturés de la famille omega 3 (précurseur ALA et DHA) et en vitamine D sur la composition en acides gras (AG) du plasma, des globules rouges et du cerveau ainsi que ses conséquences sur les marqueurs du statut inflammatoire, la réponse hépatique à l’insuline, l'expression de gènes impliqués dans la régulation de l'homéostasie énergétique et l’inflammation hypothalamique, chez des rats âgés préalablement soumis à une restriction alimentaire. Dans un premier temps, nous avons montré que la restriction alimentaire de trois mois, non carencée en ALA, induit une perte importante en omega3 (ALA et dérivés LCn-3) alors que le dérivé ARA de la série n-6 est peu modifié, conduisant ainsi à une élévation du statut pro-inflammatoire exprimé sous forme d’une augmentation du ratio ARA/LCn-3.Toutefois, les quatre semaines de réalimentation, notamment avec la formule contenant le mélange matière grasse laitière, colza et DHA, associé à de la caséine ou des protéines solubles du lait, restaure 1/ les valeurs de DHA du cerveau non restaurées par un régime contrôle de renutrition, 2/ augmente les valeurs des dérivés LCn-3 (EPA, DHA) à des niveaux supérieurs à ceux d’un régime contrôle non dénutris et de renutrition. Cette augmentation s’accompagne d’une réduction des valeurs d’ARA, induisant une baisse drastique dans le plasma et les globules rouges du ratio ARA/EPA. Ces formules montrent pour la première fois qu’elles peuvent induire une réduction très importante du statut inflammatoire par rapport à celui observé généralement chez les vieux rats et pourrait présenter un intérêt beaucoup plus général en prévention des pathologies associées au vieillissement, liées ou non à la dénutrition.Dans un second temps, nous avons montré que la restriction alimentaire de trois mois entraîne 1/ une augmentation de l’expression du récepteur à l'insuline dans l'hypothalamus, le foie et le tissu adipeux, accompagnée d'une augmentation du facteur pro-inflammatoire TNFα dans l’hypothalamus. Cependant, la réalimentation de quatre semaines entraîne 2/ un gain de poids similaire et maintient l’insulinosensibilité hépatique. En effet, nous avons montré, pour la première fois, qu’une réalimentation avec les régimes comportant le mélange MGLA/colza/DHA, permettrait 3/ d’augmenter la prise alimentaire et de diminuer l’inflammation hypothalamique, notamment, avec la formule complète contenant un mélange de haute teneur en protéines solubles de lait, associée à la matière grasse laitière /colza/DHA et enrichie en vitamine D. / Malnutrition related to aging is often accompanied by many metabolic disorders, including the disruption of energy homeostasis (installation of insulin resistance), fragility, decreased muscle mass and immune response deficiency. Thus, the nutritional manipulation, during aging, is considered to be a solution to prevent these disorders or to treat and limit damages. Amongst the nutrients that have been widely studied, we find the quality of proteins (or amino acids), of lipids (n-3 PUFA) and micronutrients (vitamin D).The aim of this thesis is to determine the impact of undernutrition and assess the potential of the refeeding formulas containing a high content of soluble protein of milk, associated with milk fat enriched with omega3 polyunsaturated fatty acids (ALA precursor and DHA) and vitamin D, on the fatty acid (FA) of the plasma, red blood cells and brain and its consequences on markers of inflammatory status, the hepatic response to insulin, the expression of genes involved in the regulation of energy homeostasis as well as hypothalamic inflammation, in old rats previously submitted for food restrictionAs a first step, our results showed that the dietary restriction of three months, despite being only moderately ALA deficient, induced a drastic loss omega3 (ALA and derivatives LCn-3), whereas a weak increase of ARA derived from n-6 series is observed, leading to a rise of the pro-inflammatory state expressed as an increase in the ratio ARA/LCn-3.However, we have shown that the four-week-refeeding formulas containing a blend of dairy-fat, rapeseed and DHA associated with casein or milk soluble proteins, restored 1 / DHA values of the brain not previously restored by the refeeding control diet, 2 /increases the values of LCn-3 derivatives (EPA, DHA) to levels above those obtained with the control non-malnourished and refeeding diets. This increase was accompanied by a reduction in ARA values, leading to a drastic drop in plasma and red blood cells ratio ARA / EPA. These formulas show for the first time that they can induce a very significant reduction of inflammatory status compared to that usually seen in old rats and could therefore present a more general interest in prevention of ageing diseases associated or not to undernutrition.In a second step, our results showed that dietary restriction of three months resulted 1/increased expression of the insulin receptor in the hypothalamus, liver and adipose tissue, accompanied by an increase of the proinflammatory factor TNF in the hypothalamus. However, the four-weeks-refeeding produces 2/ a similar weight gain and maintains hepatic insulin sensitivity. Indeed, we showed, for the first time, that refeeding, with diets containing the blend of dairy-fat / rapeseed / DHA, would 3/ increase food intake and decrease the hypothalamic inflammation, especially with the full formula containing a mixture of high content of soluble milk proteins, associated with dairy-fat / rapeseed / DHA fortified with vitamin D.

L’optimisation du statut tissulaire en acides gras polyinsaturés à longues chaines n-3 (AGPILC n-3) fait partie des objectifs actuels en nutrition humaine. En effet, de nombreux effets bénéfiques sur la santé humaine ont été démontrés pour ces différents AGPILC n-3. Néanmoins, la bioconversion de ces dérivés à partir de leur précurseur alimentaire, l’acide α-linolénique, est limitée chez l’Homme et ne permet pas de subvenir aux besoins. Parmi cette famille d’acides, l’acide docosahexaénoïque (DHA) et de l’acide eicosapentaénoïque (EPA) ont été largement étudiés à l’inverse de ceux de l’acide docosapentaénoïque n-3 (DPA). Le premier objectif de ces travaux a été d’étudier l’impact d’une supplémentation nutritionnelle en DPA sur le métabolisme des acides gras et le métabolisme lipidique chez le rat sain. Pour cela, une méthode de purification du DPA à haute pureté et en grande quantité par chromatographie liquide a tout d’abord été mise en place. Ce résultat participe à faciliter la recherche future des effets in vivo du DPA dont la disponibilité commerciale est faible. Après sa supplémentation nutritionnelle, le DPA a été incorporé dans de multiples tissus et a impacté les compositions tissulaires en AGPILC n-3 de certains organes spécifiques comme le foie, le cœur, le poumon, la rate et le rein. Ainsi, la supplémentation en DPA pourrait être une source d’EPA, de DPA, et dans une moindre mesure de DHA. Enfin, comparé à une supplémentation en EPA ou en DHA, le DPA a été l’AGPILC n-3 le plus puissant pour améliorer la triglycéridémie et la cholestérolémie des animaux. Ces informations participeront certainement à une prise en compte plus importante du DPA tant dans les études nutritionnelles ainsi que dans l’installation des futures recommandations nutritionnelles. Le deuxième axe de recherche a porté sur la capacité d’une incorporation partielle de lipides laitiers dans le régime à augmenter le statut tissulaire en AGPI-LC n-3. L’incorporation de lipides laitiers a augmenté le statut en DHA cérébral et rétinien et le statut en DPA dans les autres tissus étudiés. De plus, l’induction de la conversion des AGPILC n-3 à partir de leur précurseur par les lipides laitiers a été complémentaire avec la supplémentation en DPA pour augmenter le statut tissulaire en AGPI-LC n-3. Ces résultats s’insèrent dans un contexte de nutrition infantile, période pendant laquelle l’incorporation des AGPI-LC n-3 est maximale dans les tissus nerveux. Ainsi, ces résultats apportent des données intéressantes tant pour les entreprises que pour les professionnels de santé pour recommander à la consommation des formules infantiles contenant des lipides laitiers. / The optimization of tissue status in n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) is one of the current goals in human nutrition. Indeed, many beneficial effects on human health have been demonstrated for these different n-3 LCPUFA. However, the bioconversion of these derivatives from their food precursor, α-linolenic acid, is limited in humans and it does not meet the needs of the organism. Among this family of fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have been widely studied in contrast to those of n-3 docosapentaenoic acid (DPA). The first objective of this work was to study the impact of dietary supplementation with DPA on fatty acid metabolism and lipid metabolism in healthy rats. For this, a method for purifying DPA with high purity and in large quantities by liquid chromatography was first established. This result helps future research of the in vivo effects of DPA, poorly commercially available. After its nutritional supplementation, DPA was incorporated into multiple tissues and it has affected the n-3 LCPUFA tissue compositions of specific organs such as the liver, heart, lung, spleen and the kidney. Thus, supplementation with DPA could be a source of EPA, DPA, and to a lesser extent DHA. Finally, compared to supplementation with EPA or DHA, DPA was the most potent n-3 LCPUFA to improve triglyceridemia and cholesterolemia in animals. This information will certainly contribute to a greater consideration of DPA both in nutritional studies and in the direction of future nutritional recommendations. The second area of ​​research focused on the ability of a partial incorporation of dairy lipids in the diet to increase the tissue status in n-3 LCPUFA. Incorporation of dairy lipids in the diet increased DHA status in brain and retina and DPA status in the other studied tissues. In addition, the induction of conversion of n-3 LCPUFA from their precursor by dairy lipid was complementary with the DPA supplementation to increase n-3 LCPUFA status in tissues. These results fit into a context of infant nutrition, during which the incorporation of n-3 LCPUFA is maximal in nervous tissues. Thus, these results provide interesting data for both companies and health professionals to recommend infant formulas containing dairy lipids for consumption.

The replacement of fossil carbon sources with green bio-oils promotes the importance of several hundred oxygenated hydrocarbons, which substantially increases the analytical effort in catalysis research. A multilinear regression is performed to correlate retention indices (RIs) and response factors (RFs) with structural properties. The model includes a variety of possible products formed during the hydrodeoxygenation of bio-oils with good accuracy (RRF2 0.921 and RRI2 0.975). The GC parameters are related to the detailed hydrocarbon analysis (DHA) method, which is commonly used for non-oxygenated hydrocarbons. The RIs are determined from a paraffin standard (C5–C15), and the RFs are calculated with ethanol and 1,3,5-trimethylbenzene as internal standards. The method presented here can, therefore, be used together with the DHA method and be expanded further. In addition to the multilinear regression, an increment system has been developed for aromatic oxygenates, which further improves the prediction accuracy of the response factors with respect to the molecular constitution (R2 0.958). Both predictive models are designed exclusively on structural factors to ensure effortless application. All experimental RIs and RFs are determined under identical conditions. Moreover, a folded Plackett–Burman screening design demonstrates the general applicability of the datasets independent of method- or device-specific parameters.