Virtual screening and in vitro evaluation of putative positive allosteric modulators of the GABAB receptor

-aminobutyric acid (GABA) is the chief inhibitory neurotransmitter of the central nervous system (CNS). GABA exhibits its function by binding to either the ionotropic GABAA receptor or the metabotropic GABAB receptor, causing a decrease in activity in the nervous system. Disruption in the GABAergic system has been associated with various neurological conditions, including Alzheimer’s disease, anxiety, depressive disorders, and epilepsy. Currently, there is only one marketed drug that work on the GABAB – receptor, on the orthosteric site to be more specific. The discovery of allosteric modulators for the G-protein coupled receptors provides a promising new strategy with potential for developing novel treatments for a variety of CNS disorders, as they allow for increased drug selectivity and potentially decreased adverse side effects. Homology models of the GABAB receptor were built due to the lack of an experimentally solved three-dimensional structure, and they were used to screen for potentially new allosteric modulators using a combination of structure-based and ligand based virtual screening (in silico) with compounds from the Molport database and DrugBank. 16 compounds were purchased for testing – 8 from each database, and were further investigated and evaluated by experimental in vitro testing. Our results indicate that we have four hits, two from each database (DrugBank: I-4 = Mefloquine and I-10 = Rivaroxaban, Molport: I-23 and I-24) where it seems like I-4, I-23 and I-24 acts like PAMs whereas I-10 acts like a NAM/antagonist. The compounds from DrugBank, especially Mefloquine is of interest due to its well-known adverse effect profile which may be linked to the GABAergic system. Further investigation and confirmation of activity at the GABAB receptor could potentially lead to development of novel drugs as well as important tools for studying the structure and function of the GABAB receptor. And at the same time be used to explain the side effects seen when using Mefloquine

Molecular modelling of interactions between antipsychotic drugs and receptors mediating antipsychotic effects and important side effects

Dopamine and serotonin are two neurotransmitters that exert their actions through mediation of dopaminergic and serotonergic receptors respectively. The receptors in focus in the current study, are the dopamine D2 and serotonin 5-HT2A receptors. Common for both receptors is that they are class A G-protein-coupled receptors consisting of seven transmembrane helices embedded in the lipid membrane of neurons. Imbalance and disruption of especially the dopamine system in the CNS may result in hallucinations, delusions, and lowered levels of motivation, which are treated with antipsychotic drugs that predominantly antagonize dopamine D2 and serotonin 5-HT2A receptors. The main aim of this thesis is to get a deeper understanding of the mechanisms of action and side effects of antipsychotics utilizing induced fit docking and molecular dynamic simulations. Our results suggest that there is a correlation between the binding affinities of the antipsychotic drugs to different aminergic receptors, and the most common side effect observed. Additionally, MD simulations revealed that antipsychotic drugs with different intrinsic activity, bind to the dopamine D2 receptor in distinct ways

Le test de précipitation en milieu réduit : une alternative au test d’Emmel dans le dépistage de l’hémoglobinose S

Les hémoglobinopathies sont définies par la présence d’anomalies qualitatives et/ou quantitatives touchant les chaînes de globine. Les anomalies qualitatives sont de loin les plus fréquemment observées avec en tête la drépanocytose. L’objectif de ce travail était, de montrer l’efficacité du test de précipitation en milieu réduit (TPMR) par rapport au test d’Emmel (TE) dans le diagnostic de l’hémoglobinose S. Ainsi, sur les prélèvements sanguins de 415 sujets, sans distinction de sexe, nous avons réalisé en triple aveugle le test d’Emmel, le test de précipitation en milieu réduit et l’électrophorèse de l’hémoglobine sur gel d’agarose à pH = 6,0 ± 0,2 comme technique de référence. L’hémoglobinose S a été retrouvée à 23,4% à l’électrophorèse de l’hémoglobine dans notre échantillon. Le TPMR avait les caractéristiques suivantes : sensibilité (98%), spécificité (100%), valeur prédictive positive (100%), valeur prédictive négative (99,40%) et indice de Youden (0,99). Le TE avait une sensibilité de 92,80%, une spécificité de 98,70%, une valeur prédictive positive de 95,70%, une valeur prédictive négative de 98%, et un indice de Youden de 0,92. Le TPMR peut remplacer le TE dans les laboratoires où l’électrophorèse de l’hémoglobine n’est pas réalisable. © 2010 International Formulae Group. All rights reserved.Mots clés : Hémoglobinopathie, Technique, Electrophorèse de l’hémoglobine, TPMR, TE

Aides publiques étrangères, gouvernance et terrorisme en Afrique de l'ouest : quelles implications ?

This study aims to analyze the relationships between foreign public aid, governance and terrorism in West Africa, exploring the economic, political and security implications. The results indicate that foreign aid has a positive influence on governance, regardless of the country's group affiliation. The findings also show that aid has a generally positive impact on per capita income. However, in countries severely affected by terrorism (Burkina Faso, Mali, Niger, Nigeria), aid negatively affects economic growth and the frequency of attacks but has no impact on military expenditures. The results underscore the importance of robust economic development policies through employment opportunities, good governance practices, and regional cooperation in the fight against terrorism

Aides publiques étrangères, gouvernance et terrorisme en Afrique de l'ouest : quelles implications ?

This study aims to analyze the relationships between foreign public aid, governance and terrorism in West Africa, exploring the economic, political and security implications. The results indicate that foreign aid has a positive influence on governance, regardless of the country's group affiliation. The findings also show that aid has a generally positive impact on per capita income. However, in countries severely affected by terrorism (Burkina Faso, Mali, Niger, Nigeria), aid negatively affects economic growth and the frequency of attacks but has no impact on military expenditures. The results underscore the importance of robust economic development policies through employment opportunities, good governance practices, and regional cooperation in the fight against terrorism

Diversité et dynamique des assemblages phytoplanctoniques dans les écosystèmes aquatiques au Sud du Togo

L'étude de la diversité algale de 4 écosystèmes aquatiques du Sud-Ouest du Togo a permis l'identification de 203 espèces dont une centaine est signalée pour la première fois au Togo. Ces espèces sont réparties en 6 embranchements, 29 familles et 85 genres. L’appréciation de la dynamique du phytoplancton a permis de constater que la densité de la population algale est plus importante en grande saison pluvieuse qu’en grande saison sèche. Son importance est encore beaucoup moindre en petite saison sèche qu’en petite saison pluvieuse. Quatre paramètres physico-chimiques sont mesurés. Les analyses multivariées montrent que ces paramètres physico-chimiques affectent plus ou moins la distribution spatiale du peuplement algal. Relativement aux groupes phytoplanctoniques identifiés, plus de 70% des Euglénophytes sont rencontrés dans les mares. Par ailleurs, le peuplement phytoplanctonique lagunaire est à 58% composé des Chromophytes et celui de la rivière est dominé par les Chlorophytes (40%) et les Cyanophytes (30%).Mots-clés : diversité algale, dynamique, paramètres physico-chimiques, écosystèmes aquatiques, Sud du Togo.Diversity and dynamic of phytoplankton assemblages in the aquatic ecosystems in south of TogoThe study of algal diversity of four aquatic ecosystems in Togo’s southwestern led to the identification of 203 species including a hundred which is reported for the first time in Togo. These species are divided into 6 phyla, 29 families and 85 genera. The appreciation of the dynamics of phytoplankton showed that the algal population density is higher in long rainy season than dry season. Its importance is much lower in short dry season than in small rainy season. Four physico-chemical parameters are measured. Multivariate analysis showed that these physico-chemical parameters affect greater or lesser the spatial distribution of algal assemblage. In this study, more than 70% of Euglenophyta met in ponds. In addition, the settlement lagoon phytoplankton is composed of 58% Chromophyta and the river is dominated by Chlorophyta (40%) and Cyanophyta (30%).Keywords : algal diversity, dynamic, physico-chemical parameters, aquatic ecosystems, South of Togo

Investigation d´une épidémie de coqueluche dans le district sanitaire Tahoua département, Région de Tahoua, Niger, 2019: Etude descriptive des cas: Investigation of a pertussis epidemic in the Tahoua department health district, Tahoua region, Niger, 2019: Descriptive case study

Introduction: Au Niger, chaque année des épidémies de coqueluche sont rapportées. De 2015 à 2019, le pays a enregistré 2184 cas suspects de coqueluche. Le 27 février 2019, le CSI d'Afalla a notifié un nombre inhabituel des cas de toux quinteuse. Nous avons investigué un foyer épidémique dans le District Sanitaire (DS) Tahoua département en vue de confirmer, décrire les cas et de mettre en place des actions de santé publique. L'objectif était de décrire les résultats de cette investigation. Méthodes: Il s'agissait d'une étude transversale descriptive du 28 février au 12 mars 2019. L'ensemble de la population du Centre de Santé Intégré (CSI) de Affala a été considéré. Un cas probable était toute personne résidant dans l'aire du CSI de Affala du 17 au 12 mars 2019 présentant une toux d'une durée ≥2 semaines, avec vomissements post-tussifs. Un questionnaire structuré a été administré aux malades ou aux mères ou accompagnants des nourrissons. Une revue documentaire et une recherche active des cas ont été réalisées. Résultats: Au total, 108 cas de coqueluche ont été enregistrés. Aucun décès n'a été notifié. Le sexe masculin représentait 60,2% des cas. L'âge médian était de 7 ans intervalle interquartile IIQ (2-14 ans). Parmi les cas, 17(15,7%) étaient âgés de moins de 5 ans. Deux villages du CSI Affala ont enregistré des cas. Tous les enfants présentaient une toux et 14,8% des cas étaient vaccinés. La durée de l'épidémie était de 14 jours. Conclusion: L' investigation de cette épidémie a permis de décrire les cas et mettre en place des mesures de contrôle et de prévention. La vaccination de routine contre la coqueluche devrait être renforcée. Introduction: In Niger, every year outbreaks of pertussis are reported. From 2015 to 2019, the country has recorded 2184 suspected cases of pertussis. On 27 February 2019, the Afalla IHC reported an unusual number of cases of whooping cough. We investigated an outbreak in the Tahoua Health District (HD) department in order to confirm and describe the cases and to implement public health actions. The objective was to describe the results of this investigation. Methods: This was a descriptive cross-sectional study from 28 February to 12 March 2019. The entire population of the Affala Integrated Health Centre (IHC) was considered. A probable case was any person residing in the Affala IHC area from 17 to 12 March 2019 presenting with a cough lasting ≥2 weeks, with post-cough vomiting. A structured questionnaire was administered to the patients or mothers/caregivers of infants. A literature review and active case finding were performed. Result: In total, 108 cases of pertussis were recorded. No deaths were reported. Males accounted for 60.2% of the cases. The median age was 7 years, interquartile range IIQ (2-14 years). Of the cases, 17 (15.7%) were under 5 years of age. Two villages in Affala IHC had cases. All children had a cough and 14.8% of cases were vaccinated. The duration of the epidemic was 14 days. Conclusion: The investigation of this epidemic allowed us to describe the cases and to put in place control and prevention measures. Routine vaccination against pertussis should be reinforced

Hybridizing political criticism in the postcolonial African novel: magical realism as aesthetics of necessity

This dissertation examines the use of magical realism as a device for political criticism in the postcolonial African novel as seen in the works of of Kojo B. Laing, Ben Okri, and Ngugi wa Thiong'o, namely Woman of the Aeroplanes, The Famished Road, and Wizard of the Crow, respectively. I argue that, in these novels, magical realism is not merely a literary mode; rather, it is an aesthetic of necessity. In other words, its use by these postcolonial African writers is dictated by the kind of issues they address in their works. Magical realism is the result of an intentional break away from the modes used in the previous African novels. This departure is informed by the realization of the current generation of postcolonial African writers that the social, political, and economic situations in Africa have extraordinary origins which require extraordinary narrative techniques such as fantastical or marvelous realism for adequate representations. In other words, their choice of magical realism is informed by their dissatisfaction with social realism, satire, and other forms which have revealed their limits vis-àvis the postcolonial African crisis. Because of the postcolonial critics' tendency to assess all magical realist texts with the same criteria, this dissertation emphasizes how the socio-cultural milieus on which the authors I examine draw variously shape their individual magical realist texts. Chapter One discusses magical realism as aesthetic of necessity from its original application to art criticism to its current intervention in the postcolonial literary criticism. Chapter Two discusses Laing's use of a utopian-grounded existentialist magical realism to create limitless possibilities for the creation of a new Africa. Chapter Three focuses on Okri's use of the "abiku" myth to describe the condition of post-independence Africa in general, and Nigeria in particular. Finally, Chapter Four examines how Ngugi draws on Gikuyu folklore to create fabulous realism and satirical magical realism for his depiction of the social, economic, and political situations of postcolonial Kenya and Africa

UC-16 Understanding the Drivers of Medication Nonadherence in the United States

Medication nonadherence is generally defined as a patient’s inability to take their medications correctly as prescribed by their doctors. Medication nonadherence adversely affects patient outcomes and increases healthcare costs. Prior research found that health system-, condition-, patient- (older age is one factor), therapy- and social/economic-related factors have been identified to show effect on non-adherence. Our goal is to analyze the NHIS data to understand the sociodemographic and health causes of medication nonadherence, as well as answer the following questions about our selected topic: What variables are the most relevant drivers of nonadherence? Does the direction and strength of the associations between these variables and medication nonadherence vary over time? If so, how? Are trends getting better or worse? Do the results of your analysis suggest that social inequality factors may be linked to medication nonadherence? If so, how? What are the implications of your analysis for various stakeholders? How does this vary depending on whether medication nonadherence is intentional or unintentional?Advisors(s): Advisor/Instructor: Ying Xie | [email protected] Project Owner/Sponsor: Dr. Chi Zhang | [email protected](s): Data/Data AnalyticsIT4893 - IT Capstone (W01