Tackling health inequalities in primary care: an exploration of GPs’ experience at the frontline

In Scotland, life expectancy and health outcomes are strongly tied to socioeconomic status. Specifically, socioeconomically deprived areas suffer disproportionately from high levels of premature multimorbidity and mortality. To tackle these inequalities in health, challenges in the most deprived areas must be addressed. One avenue that merits attention is the potential role of general medical practitioners (GPs) in helping to address health inequalities, particularly due to their long-term presence in deprived communities, their role in improving patient and population health, and their potential advocacy role on behalf of their patients. GPs can be seen as what Lipsky calls ‘street-level bureaucrats’ due to their considerable autonomy in the decisions they make surrounding individual patient needs, yet practising under the bureaucratic structure of the NHS. While previous research has examined the applicability of Lipsky’s framework to the role of GPs, there has been very little research exploring how GPs negotiate between the multiple identities in their work, how GPs ‘socially construct’ their patients, how GPs view their potential role as ‘advocate’, and what this means in terms of the contribution of GPs to addressing existing inequalities in health. Using semi-structured interviews, this study explored the experience and views of 24 GPs working in some of Scotland’s most deprived practices to understand how they might combat this growing health divide via the mitigation (and potential prevention) of existing health inequalities. Participants were selected based on several criteria including practice deprivation level and their individual involvement in the Deep End project, which is an informal network comprising the 100 most deprived general practices in Scotland. The research focused on understanding GPs’ perceptions of their work including its broader implications, within their practice, the communities within which they practise, and the health system as a whole. The concept of street-level bureaucracy proved to be useful in understanding GPs’ frontline work and how they negotiate dilemmas. However, this research demonstrated the need to look beyond Lipsky’s framework in order to understand how GPs reconcile their multiple identities, including advocate and manager. As a result, the term ‘street-level professional’ is offered to capture more fully the multiple identities which GPs inhabit and to explain how GPs’ elite status positions them to engage in political and policy advocacy. This study also provides evidence that GPs’ social constructions of patients are linked not only to how GPs conceptualise the causes of health inequalities, but also to how they view their role in tackling them. In line with this, the interviews established that many GPs felt they could make a difference through advocacy efforts at individual, community and policy/political levels. Furthermore, the study draws attention to the importance of practitioner-led groups—such as the Deep End project—in supporting GPs’ efforts and providing a platform for their advocacy. Within this study, a range of GPs’ views have been explored based on the sample. While it is unclear how common these views are amongst GPs in general, the study revealed that there is considerable scope for ‘political GPs’ who choose to exercise discretion in their communities and beyond. Consequently, GPs working in deprived areas should be encouraged to use their professional status and political clout not only to strengthen local communities, but also to advocate for policy change that might potentially affect the degree of disadvantage of their patients, and levels of social and health inequalities more generally.

Implication of gut microbiota in nonalcoholic fatty liver disease

International audience

Análise filogenética e funcional de dois genes de reparo homólogos a AP endonuclease em cana-de-açúcar: ScARP1 e ScARP3

The genome of all organisms constantly suffers the influence of mutagenic factors from endogenous and/or exogenous origin, which may result in damage for the genome. In order to keep the genome integrity there are different DNA repair pathway to detect and correct these lesions. In relation to the plants as being sessile organisms, they are exposed to this damage frequently. The Base Excision DNA Repair (BER) is responsible to detect and repair oxidative lesions. Previous work in sugarcane identified two sequences that were homologous to Arabidopsis thaliana: ScARP1 ScARP3. These two sequences were homologous to AP endonuclease from BER pathway. Then, the aim of this work was to characterize these two sequence using different approaches: phylogenetic analysis, in silico protein organelle localization and by Nicotiana tabacum transgenic plants with overexpression cassette. The in silico data obtained showed a duplication of this sequence in sugarcane and Poaceae probably by a WGD event. Furthermore, in silico analysis showed a new localization in nuclei for ScARP1 protein. The data obtained with transgenic plants showed a change in development and morphology. Transgenic plants had slow development when compared to plants not transformed. Then, these results allowed us to understand better the potential role of this sequence in sugarcane and in plants in general. More work is important to be done in order to confirm the protein localization and protein characterization for ScARP1 and ScARP3

Influence of Acute and Chronic Exercise on Markers of Hippocampal Plasticity

Exercise and physical activity are lifestyle behaviors associated with enriched mental health. Understanding the mechanisms by which exercise and physical activity improve mental health may provide insight for novel therapeutic approaches for numerous mental health disorders. This dissertation reports the findings from three studies investigating the influence of acute and chronic exercise on behavioral and mechanistic markers of hippocampal plasticity and delves into the potential role of noradrenergic signaling in the hippocampal adaptations with exercise. The first study assessed the effects of long-term voluntary wheel running on hippocampal expression of plasticity-associated genes and proteins in adult male and female C57BL/6J mice, highlighting sex differences in the adaptations to long-term voluntary wheel running. The second study examined the influence of acute exercise intensity on AMPA receptor phosphorylation, a mechanism essential for hippocampal plasticity, plasticity- associated gene expression, spatial learning and memory, and anxiety-like behavior. The unexpected finding that acute exercise increased anxiety-like behavior encouraged investigation into the role of central noradrenergic signaling in acute exercise-induced anxiety. The third study determined how previous exposure to voluntary wheel running modulates the response to an acute bout of exercise, focusing primarily on transcription of the important plasticity-promoting gene, brain-derived neurotrophic factor. Using a pharmacological approach to compromise the locus coeruleus noradrenergic system, a system that is implicated in age-related mental health disorders such as Alzheimer’s Disease, the third study also investigated the influence and interaction of the noradrenergic system and acute exercise on expression of multiple brain-derived neurotrophic factor transcripts. Together, this dissertation reports the findings from a series of experiments that explored similarities, differences, and interactions between the effects of acute and chronic exercise on markers of hippocampal plasticity and behavior. Further, this work provides insight into the role of the noradrenergic system in exercise-induced hippocampal plasticity.

Association of TNF-α Gene Variants With Clinical Manifestation of Cystic Fibrosis Patients of Iranian Azeri Turkish Ethnicity

Background: Cystic fibrosis (CF), a life-limiting autosomal recessive disorder, is considered a monogenic disease that is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. According to several studies, mutation analysis of the cystic fibrosis transmembrane conductance regulator (CFTR) gene alone is insufficient to predict the phenotypic manifestations observed in cystic fibrosis (CF) patients. In addition, some patients with a milder CF phenotype do not carry any pathogenic mutation. Tumor Necrosis Factor-alpha (TNF-α) contributes to the pathophysiology of CF by causing cachexia. There is a reverse association between TNF-α concentration in patient's sputum and their pulmonary function. Objectives: To assess the effect of non-CFTR genes on the clinical phenotype of CF, two polymorphic sites (-1031T/C and -308G/A) of the TNF-α gene, as a modifier, were studied. Patients and Methods: Focusing on the lung and gastrointestinal involvement as well as the poor growth, we first investigated the role of TNF-α gene in the clinical manifestation of CF. Furthermore, based on the hypothesis that the cumulative effect of specific alleles of multiple CF modifier genes, such as TNF-α, may create the final phenotype, we also investigated the potential role of TNF-α in non-classic CF patients without a known pathogenic mutation. In all, 80 CF patients and 157 healthy control subjects of Azeri Turkish ethnicity were studied by the PCR–RFLP method. The chi-square test with Yates' correction and Fisher's exact test were used for statistical analysis. Results: The allele and genotype distribution of the investigated polymorphisms, and their associated haplotypes were similar in all groups. Conclusions: There was no evidence that supported the association of TNF-α gene polymorphisms with non-classic CF disease or the clinical presentation of classic CF.

Caracterização da variação do índice de resistência renal e o seu potencial papel como fator de diagnóstico precoce na doença renal em Felis catus

Dissertação de Mestrado Integrado em Medicina Veterinária

Moderating effects of gender in the relationships between daily stress, coping styles and hopelessness depression in adolescents

The hopelessness depression (HD) theory assumes a number of contributing factors to the development of hopelessness expectations and HD symptoms. Studies carried out to test HD theory have generally supported the prediction that a negative attributional style contributes to the development of hopelessness expectations and HD symptoms, although the evidence is less consistent for adolescents. Due to these inconsistent results, as well as the assumption advanced by HD theory that other factors aside from attributional style may contribute to the development of HD, in this study we examined the potential role of adolescents’ daily stress and coping styles as contributing factors to HD at these ages, and the effects of gender on these relationships. Seiffge-Krenke (1995) showed that stress in daily life plays a particularly relevant role during adolescence and described three coping styles used by adolescents to face daily stress: active and internal approach-oriented styles, which are considered functional and complementary, and avoidant style, considered dysfunctional. In this study, secondary students (N = 480; aged 13–17) completed the Hopelessness Scale (Beck, Weissman, Lester, & Trexler, 1974), the Hopelessness Depression Symptoms Questionnaire (Metalsky & Joiner, 1997), the Problem Questionnaire ((Seiffge-Krenke, 1995) and the Coping Across Situations Questionnaire (Seiffge-Krenke, 1995). To test the role of daily stress and coping styles in the prediction of hopelessness expectations and HD symptoms, two four-step hierarchical multiple regression analyses were conducted. In these analyses, gender was introduced first, daily stress was introduced second, the three coping styles were entered in a third step, and the moderating effects of gender on the associations of the predictor variables (daily stress and each coping style) with the criterion variables (hopelessness expectations or HD symptoms) were introduced in a fourth step. Results showed a moderating effect of gender on the relationship between daily stress and hopelessness expectations, which revealed a significant effect for boys despite the fact that girls experienced more daily stress than boys, thus suggesting an inoculation effect in girls. It was also found a gender-dependent role of coping styles in the prediction of HD symptoms, revealing a protective effect for the active style in girls and for the internal style in boys. This suggests that girls would benefit from being more action-prone and boys more reflection-prone in order to prevent HD. These findings indicate that programmes aimed to promote coping skills in adolescents would benefit from being gender-adapted.

GIS-integrated mathematical modeling of social phenomena at macro- and micro- levels—a multivariate geographically-weighted regression model for identifying locations vulnerable to hosting terrorist safe-houses: France as case study

Adaptability and invisibility are hallmarks of modern terrorism, and keeping pace with its dynamic nature presents a serious challenge for societies throughout the world. Innovations in computer science have incorporated applied mathematics to develop a wide array of predictive models to support the variety of approaches to counterterrorism. Predictive models are usually designed to forecast the location of attacks. Although this may protect individual structures or locations, it does not reduce the threat—it merely changes the target. While predictive models dedicated to events or social relationships receive much attention where the mathematical and social science communities intersect, models dedicated to terrorist locations such as safe-houses (rather than their targets or training sites) are rare and possibly nonexistent. At the time of this research, there were no publically available models designed to predict locations where violent extremists are likely to reside. This research uses France as a case study to present a complex systems model that incorporates multiple quantitative, qualitative and geospatial variables that differ in terms of scale, weight, and type. Though many of these variables are recognized by specialists in security studies, there remains controversy with respect to their relative importance, degree of interaction, and interdependence. Additionally, some of the variables proposed in this research are not generally recognized as drivers, yet they warrant examination based on their potential role within a complex system. This research tested multiple regression models and determined that geographically-weighted regression analysis produced the most accurate result to accommodate non-stationary coefficient behavior, demonstrating that geographic variables are critical to understanding and predicting the phenomenon of terrorism. This dissertation presents a flexible prototypical model that can be refined and applied to other regions to inform stakeholders such as policy-makers and law enforcement in their efforts to improve national security and enhance quality-of-life.

Assessment of genetic diversity of zoonotic Brucella spp. recovered from livestock in Egypt using multiple locus VNTR analysis

Brucellosis is endemic in most parts of Egypt, where it is caused mainly by Brucella melitensis biovar 3, and affects cattle and small ruminants in spite of ongoing efforts devoted to its control. Knowledge of the predominant Brucella species/strains circulating in a region is a prerequisite of a brucellosis control strategy. For this reason a study aiming at the evaluation of the phenotypic and genetic heterogeneity of a panel of 17 Brucella spp. isolates recovered from domestic ruminants (cattle, buffalo, sheep, and goat) from four governorates during a period of five years (2002-2007) was carried out using microbiological tests and molecular biology techniques (PCR, MLVA-15, and sequencing). Thirteen strains were identified as B. melitensis biovar 3 while all phenotypic and genetic techniques classified the remaining isolates as B. abortus (n = 2) and B. suis biovar 1 (n = 2). MLVA-15 yielded a high discriminatory power (h = 0.801), indicating a high genetic diversity among the B. melitensis strains circulating among domestic ruminants in Egypt. This is the first report of the isolation of B. suis from cattle in Egypt which, coupled with the finding of B. abortus, suggests a potential role of livestock as reservoirs of several zoonotic Brucella species in the region.

Prevalence of Escherichia coli Virulence Genes in Patients with Diarrhea and a Subpopulation of Healthy Volunteers in Madrid, Spain

Etiological diagnosis of diarrheal diseases may be complicated by their multi-factorial nature. In addition, Escherichia coli strains present in the gut can occasionally harbor VGs without causing disease, which complicates the assessment of their clinical significance in particular. The aim of this study was to detect and quantify nine VGs (stx1, stx2, eae, aggR, ehxA, invA, est and elt) typically present in five E. coli enteric pathotypes (EHEC, ETEC, EPEC, EAEC and EIEC) in fecal samples collected from 49 patients with acute diarrhea and 32 healthy controls from Madrid, Spain. In addition, the presence of four serotype-related genes (wzxO104 and fliCH4, rbfO157 and fliCH7) was also determined. Presence of target genes was assessed using a quantitative real-time PCR assay previously developed, and the association of presence and burden of VGs with clinical disease and/or other risk factors was explored. Prevalence of ehxA (typically associated with STEC and EPEC), invA (EIEC) and the rbfO157+fliCH7 (STEC and/or STEC/EAEC) combination were significantly (p<0.02) higher in the diarrheic group, while the wzxO104+fliCH4 combination was significantly (p=0.014) more prevalent in the control group. On the other hand, eae was detected in more than 90% of the individuals in both patient and control populations, and it was not associated with bfpA, suggesting the absence of typical EPEC. No significant differences in the quantitative values were detected for any VG among study groups, but the difference in the load of aggR (EAEC) and invA in the patients with respect to the controls was close to the significance, suggesting a potential role of these VGs in the clinical signs observed when they are present at high levels.

Toxicity of polychlorinated biphenyls and N-phenyl-1-naphthylamine in the juvenile turtle, Chelydra serpentina

Polychlorinated biphenyls (PCBs) and substituted phenylamine antioxidants (SPAs) are two chemical groups that have been used in multiple Canadian industrial processes. Despite the production ban of PCBs in North America in 1977, they are still ubiquitous in the environment and in wildlife tissues. Previous studies of fish, amphibians, birds, and mammals have shown that PCBs are toxic and act as endocrine disruptors. In contrast, SPAs, specifically N-phenyl-1-naphthylamine (PANA), have received very little attention despite their current use in Canada and their expected environmental releases. The effects of PCB and PANA exposures in reptiles remain unknown thus, juvenile Chelydra serpentina were used in this thesis as a model vertebrate to fill in missing toxicity research gaps due to their importance as an environmental indicator. First, food pellets were spiked at an environmentally relevant concentration of the PCB mixture Aroclor 1254 (A1254) to model hepatic bioaccumulation (0.45 μg/g A1254 for 31 days) and depuration (clean food for 50 days) of PCBs in turtles. No significant differences in PCB concentrations were observed between the control and treated animals, suggesting that juvenile turtles exposed to environmentally relevant concentrations of PCBs can likely detoxify low concentrations of PCBs. Additionally, two dose-response experiments were performed using A1254 or PANA spiked food (0-12.7 μg/g and 0-3,446 μg/g, respectively) to determine hepatic toxicity and bioaccumulation in juvenile C. serpentina. An increase in hepatic cyp1a was observed when exposed to the highest dose of both chemicals: 1) for A1254, induction correlated to the significant increase in hepatic PCB congeners that are known to be metabolized by CYP1A; and 2) for PANA, induction suggested that CYP1A has a potential role in its detoxification. PCBs are known endocrine disruptors, but no significant changes were observed for both thyroid receptors (alpha and beta) or by estrogen and androgen receptors. This lack of response, also noted in the PANA exposure, suggests that C. serpentina is less sensitive to endocrine disruption than other vertebrates. Furthermore, the expression of genes involved in cellular stress was not altered in PCB and PANA exposed animals, supporting the resilience of turtles to oxidative stress. This is the first study to demonstrate the toxicity of PCBs and PANA in C. serpentina, demonstrating the turtle’s high tolerance to contamination.

Development of an antigen-driven colitis model to study presentation of antigens by antigen presenting cells to T cells

Inflammatory bowel disease (IBD) is a chronic inflammation which affects the gastrointestinal tract (GIT). One of the best ways to study the immunological mechanisms involved during the disease is the T cell transfer model of colitis. In this model, immunodeficient mice (RAG-/-recipients) are reconstituted with naive CD4+ T cells from healthy wild type hosts. This model allows examination of the earliest immunological events leading to disease and chronic inflammation, when the gut inflammation perpetuates but does not depend on a defined antigen. To study the potential role of antigen presenting cells (APCs) in the disease process, it is helpful to have an antigen-driven disease model, in which a defined commensal-derived antigen leads to colitis. An antigen driven-colitis model has hence been developed. In this model OT-II CD4+ T cells, that can recognize only specific epitopes in the OVA protein, are transferred into RAG-/- hosts challenged with CFP-OVA-expressing E. coli. This model allows the examination of interactions between APCs and T cells in the lamina propria.

Tourism and arctic observation systems : Exploring the relationships

The Arctic is affected by global environmental change and also by diverse interests from many economic sectors and industries. Over the last decade, various actors have attempted to explore the options for setting up integrated and comprehensive trans-boundary systems for monitoring and observing these impacts. These Arctic Observation Systems (AOS) contribute to the planning, implementation, monitoring and evaluation of environmental change and responsible social and economic development in the Arctic. The aim of this article is to identify the two-way relationship between AOS and tourism. On the one hand, tourism activities account for diverse changes across a broad spectrum of impact fields. On the other hand, due to its multiple and diverse agents and far-reaching activities, tourism is also well-positioned to collect observational data and participate as an actor in monitoring activities. To accomplish our goals, we provide an inventory of tourism-embedded issues and concerns of interest to AOS from a range of destinations in the circumpolar Arctic region, including Alaska, Arctic Canada, Iceland, Svalbard, the mainland European Arctic and Russia. The article also draws comparisons with the situation in Antarctica. On the basis of a collective analysis provided by members of the International Polar Tourism Research Network from across the polar regions, we conclude that the potential role for tourism in the development and implementation of AOS is significant and has been overlooked.

Genomics to elucidate the molecular basis of calcific aortic valve disease

Le rétrécissement valvulaire aortique (RVA) est causé par une calcification et une fibrose progressive de la valve aortique. Le risque de développer la maladie augmente avec l’âge. À cause de l’augmentation de l’espérance de vie, le RVA est devenu un problème de santé publique. Le RVA est fatal en absence de traitement médical. Actuellement, la chirurgie est le seul traitement pour le stade sévère de la maladie, mais près de 50% des individus avec RVA n’y sont pas éligibles, principalement due à la présence de comorbidités. Plusieurs processus biologiques ont été associés à la maladie, mais les voies moléculaires spécifiques et les gènes impliqués dans le développement et la progression du RVA ne sont pas connus. Il est donc urgent de découvrir les gènes de susceptibilité pour le RVA afin d’identifier les personnes à risque ainsi que les biomarqueurs et les cibles thérapeutiques pouvant mener au développement de médicaments pour inverser ou limiter la progression de la maladie. L’objectif de cette thèse de doctorat était d’identifier la base moléculaire du RVA. Des approches modernes en génomique, incluant l’étude de gènes candidats et le criblage génomique par association (GWAS), ont été réalisées à l’aide de collections d’ADN provenant d’un grand nombre de patients bien caractérisés pour le RVA. Des études complémentaires en transciptomique ont comparé le profil d’expression global des gènes entre des valves calcifiées et non-calcifiées à l’aide de biopuces à ADN et de séquençage de l’ARN. Une première étude a identifié des variations dans le gène NOTCH1 et suggère pour la première fois la présence d’un polymorphisme commun dans ce gène conférant une susceptibilité au RVA. La deuxième étude a combiné par méta-analyse deux GWAS de patients provenant de la ville de Québec et Paris (France) aux données transcriptomiques. Cette étude de génomique intégrative a confirmé le rôle de RUNX2 dans le RVA et a permis l’identification d’un nouveau gène de susceptibilité, CACNA1C. Les troisième et quatrième études sur l’expression des gènes ont permis de mieux comprendre les bases moléculaires de la calcification des valves aortiques bicuspides et ainsi d’identifier de nouvelles cibles thérapeutiques pour le RVA. Les données générées par ce projet sont la base de futures découvertes importantes qui permettront d’améliorer les options de traitement et la qualité de vie des patients atteints du RVA.

Depresión en pacientes con epilepsia: Revisión sistemática de la literatura

Esta revisión sistemática de la literatura tuvo como objetivo investigar sobre la depresión en personas con epilepsia en la última década (2005-2015), enfocándose en identificar en el paciente con epilepsia: características sociodemográficas, prevalencia de la depresión, tipos de intervención para el manejo de la depresión, factores asociados con la aparición y el mantenimiento de la depresión y por último, identificar las tendencias en investigación en el estudio de la depresión en pacientes con epilepsia. Se revisaron 103 artículos publicados entre 2005 y 2015 en bases de datos especializadas. Los resultados revelaron que la prevalencia de depresión en pacientes con epilepsia es diversa y oscila en un rango amplio entre 3 y 70 %, por otro lado, que las principales características sociodemográficas asociadas a la depresión está el ser mujer, tener un estado civil soltero y tener una edad comprendida entre los 25 y los 45 años. A esto se añade, que los tratamientos conformados por terapia psicológica y fármacos, son la mejor opción para garantizar la eficacia en los resultados del manejo de la depresión en los pacientes con epilepsia. Con respecto a los factores asociados a la aparición de la depresión en pacientes con epilepsia, se identificaron causas tanto neurobiológicas como psicosociales, asimismo los factores principales asociados al mantenimiento fueron una percepción de baja calidad de vida y una baja auto-eficacia. Y finalmente los tipos de investigación más comunes son de tipo aplicado, de carácter descriptivo, transversales y de medición cuantitativa.