Etude des interactions des peptides beta-amyloïdes et membranes cellulaires : transport et toxicité

Alzheimer's disease has become the most important degenerative disorder in elderly people, being cognitive decline its main result for patients who exhibit such medical condition. A hallmark of this disease is the brain accumulation of amyloïd peptides, particulary Aβ42 peptide, wich is revealed to be the most toxic. This peptide must be eliminated of brain, and the transporter P-glycoprotein at the blood brain barrier (BBB) has been proposed for this process. The principal aim of this thesis was to know if Aβ42 is transported by P-gp. Our results suggested that such transport mechanism di not seem to be possible.In order to explore the underlying changes that drive neuronal death in Alzheimer's disease, a study of variations in two parameters importants for cell survival (membrane potential and intracellular concentration of chloride) has been made. Alterations in theses parameters were observed in neuronal cells incubated in the presence of Aβ42 . Finally, a study on inhibitor effect of different molecules on P-gp activity completes this thesis, to accomplish the aim understanding molecules interactions with P-gp, so as to establish some possible guidelines related with new treatments for Alzheimer's disease. The overall results obtained in the three studies herein contribute to understand the development of this disease.La maladie d'Alzheimer est devenue le désordre neurodégénérarif le plus important chez les personnes âgées chez qui elle se manifeste par un déclin cognitif. Cette maladie se caractérise par l'accumulation dans le cerveau de peptides amyloïdes, particulièrement le peptide Aβ42, qui s'avère être le plus toxique. Ce peptide doit être éliminé du cerveau et le transporteur P-glycoprotéine présent dans la Barrière Hémato Encéphalique (BHE) a été proposé comme intervenant dans ce processus. L'objectif essentiel de cette thèse, était de savoir si le peptide Aβ42 est pris en charge par la P-gp. Nos résultats suggèrent que ce transport semble ne pas être possible. Dans le but d'explorer quels sont les changements conduisant à la mort neuronale lors de la maladie d'Alzheimer, une étude sur la modification de deux paramètres contribuant à la vie cellulaire a été aussi réalisée, a savoir : le potentiel membranaire et la concentration intercellulaire des ions chlorure. Des altérations dans ces deux paramètres ont été observées lors de l'incubation des cellules neuronales avec Aβ42. Finalement afin de mieux comprendre l'interaction des molécules avec la P-gp pouvant aboutir à la conception de nouveaux traitements pour la maladie d'Alzheimer, une étude sur l'effet inhibiteur de différentes molécules sur la P-gp parachève cette thèse. Les résultats obtenus lors de ces trois études portent une contribution à la compréhension dans le domaine du développement de cette maladie

Performance assessment of a kinetically-powered network for herd localization

Developing a herd localization system capable to operate unattended in communication-challenged areas arises from the necessity of improving current systems in terms of cost, autonomy or any other facilities that a certain target group (or overall users) may demand. A network architecture of herd localization is proposed with its corresponding hardware and a methodology to assess performance in different operating conditions. The system is designed taking into account an eventual environmental impact hence most nodes are simple, cheap and kinetically powered from animal movements-neither batteries nor sophisticated processor chips are needed. Other network elements integrating GPS and batteries operate with selectable duty cycles, thus reducing maintenance duties. Equipment has been tested on Scandinavian reindeer in Lapland and its element modeling is integrated into a simulator to analyze such localization network applicability for different use cases. Performance indicators (detection frequency, localization accuracy and delay) are fitted to assess the overall performance; system relative costs are enclosed also for a range of deployments

Improved Animal Tracking Algorithm using Distributed Kalman Filter-based Algortihms

Animal tracking has been addressed by different initiatives over the last two decades. Most of them rely on satellite connectivity on every single node and lack of energy-saving strategies. This paper presents several new contributions on the tracking of dynamic heterogeneous asynchronous networks (primary nodes with GPS and secondary nodes with a kinetic generator) motivated by the animal tracking paradigm with random transmissions. A simple approach based on connectivity and coverage intersection is compared with more sophisticated algorithms based on ad-hoc implementations of distributed Kalman-based filters that integrate measurement information using Consensus principles in order to provide enhanced accuracy. Several simulations varying the coverage range, the random behavior of the kinetic generator (modeled as a Poisson Process) and the periodic activation of GPS are included. In addition, this study is enhanced with HW developments and implementations on commercial off-the-shelf equipment which show the feasibility for performing these proposals on real hardware

Cattle-powered nodes experience in a heterogeneous network for localization of herds

A heterogeneous network, mainly based on nodes that use harvested energy to self-energize is presented and its use demonstrated. The network, mostly kinetically powered, has been used for the localization of herds in grazing areas under extreme climate conditions. The network consists of secondary and primary nodes. The former, powered by a kinetic generator, take advantage of animal movements to broadcast a unique identifier. The latter are battery-powered and gather secondarynode transmitted information to provide it, along with position and time data, to a final base station in charge of the animal monitoring. Because a limited human interaction is desirable, the aim of this network is to reduce the battery count of the system

Autotransplantation, Surgical Repositioning of Retained Canine, and Apical Filling of Two Incisors with Root Resorption

The purpose is to show the autotransplantation and surgical repositioning of a retained canine, and the apical filling of central and lateral resorbed incisors from a 12-year-old female patient, healthy and with clinical absence of left maxillary canine. Radiographically, the retained canine between the resorbed central and lateral incisors was observed. Root canal treatment of the canine was performed after 8 weeks; apical curettage and placement of bovine graft in inter-incisal zone was done after 4 months. During 6 months, orthodontic traction of the canine was carried out with no positive results, and 12 months after the autotransplantation, surgical repositioning was performed. Clinical-radiographic control at 30 days and 24 months showed absence of inflammation, restoration and integration of the tooth-supporting structures. Autotransplantation combined with surgical repositioning of the retained canine and the apical filling of two incisors achieved the harmonious, aesthetic, functional, dental and psychological preservation of the patient.Keywords: Autotransplantation; Endodontics; Endodontic Surgery; Root Resorption; Surgical Repositionin

COVID-19 grave en el contexto de una población vacunada: Estudio de casos y controles

Justificación y Objetivos: Desde su aparición en 2019, se han identificado múltiples factores de riesgo para presentar una forma grave de COVID-19 y también se han desarrollado distintas vacunas que previenen la aparición de manifestaciones de gravedad. Sin embargo, a pesar del antecedente de vacunación, algunos casos se complican o incluso fallecen. El objetivo del este estudio fue determinar la fuerza de asociación entre la gravedad de la COVID-19 con el antecedente de vacunación en pacientes atendidos en un hospital público de referencia de la Ciudad de México. Métodos: Estudio epidemiológico no experimental, retrospectivo y analítico, de casos y controles. La población de estudio fueron personas atendidas en un hospital de concentración para la atención de COVID-19 entre el 1 de julio de 2021 y el 30 de junio de 2022 en la Ciudad de México. Resultados: 132 participantes (44 casos y 88 controles) fueron incluidos en el estudio. Los factores de riesgo más fuertemente asociados con la gravedad de la COVID-19 fueron la edad mayor o igual a 60 años, presentar 22 respiraciones por minuto en la primera valoración médica, tensión arterial sistólica mayor o igual a 140 milímetros de mercurio y el antecedente de al menos una comorbilidad crónica. No obstante, el antecedente de vacunación se asoció con 94% (RM 0.06) menos posibilidades de desarrollar COVID-19 grave con respecto a aquellos sin antecedente vacunal, independientemente de la presencia de los factores de riesgo asociados. Conclusión: carecer del antecedente de vacunación y presentar alguno de los factores de riesgo identificados confieren las mayores posibilidades de presentar formas graves de la enfermedad

Commentary on COVID-19 Vaccine Hesitancy in sub-Saharan Africa

This research was funded in part by the Bill and Melinda Gates Foundation (Grant number: OPP1075938-PEARL Program Support) awarded to Jerome Nyhalah Dinga.Peer reviewedPublisher PD