Small critical RNAs in the scrapie agent

Unconventional infectious agents cause transmissible spongiform encephalopathy (TSE) diseases including scrapie and bovine spongiform encephalopathy (BSE) in animals and Creutzfeldt-Jakob disease in humans. The protein only hypothesis claims that the TSE agent is composed solely of the protein called prion (PrP^sc^)^1^. This protein is the misfolded form of a host-encoded cellular protein, PrP^c^ exerting presumably a vital role at the synapse^2^. Even though now widely accepted, the prion concept fails to provide in certain circumstances^3-6^, a satisfying interpretation of the infectious phenomenon. Using the 263K scrapie-hamster model, we conducted a transmission study to search for a putative prion-associated factor indispensable for infectivity. Here we show that innocuous recombinant prion protein (recPrP) was capable, in a reproducible manner, of transmitting scrapie disease when the protein was [beta]–sheet converted in a solution containing PrP^sc^-derived RNA material. Analysis of the PrP-RNA mixture revealed the association of recPrP with two prominent populations of small RNA molecules having an average length of about ~27 and ~55 nucleotides. We conclude that the nature of the TSE agent seems to be composed of a nucleoprotein molecular complex, in which informative RNA molecules of small sizes are associated with the misfolded prion protein (PrP^sc^)

Mise au point de techniques analytiques pour la spéciation du sélénium dans les boues de stations d'épuration d'eaux résiduaires urbaines

Les stations d'épuration d'eaux résiduaires sont une des étapes du cycle du sélénium dans l'environnement et contribuent à sa redistribution dans le milieu naturel. Très peu étudié jusqu'à présent dans ces milieux, le sélénium n'en est pas moins un élément très important du point de vue écotoxicologique, sa teneur dans les boues de stations d'épuration destinées à l'épandage agricole faisant par ailleurs l'objet d'une norme.Nous avons mis au point des techniques permettant la détermination spécifique de l'élément total dans ce type d'échantillon, par minéralisation classique ou assistée par micro-ondes et dosage par Voltamétrie de Redissolution Cathodique Différentielle Pulsée (DPCSV) et Spectrométrie d'Absorption Atomique ElectroThermique (ETAAS). Le contrôle qualité a été effectué sur deux échantillons certifiés fournis par le Bureau Communautaire de Référence (BCR) : la boue CRM 145 R et la boue CRM 007.Cependant, lorsqu'on parle de risque toxicologique, il est important de s'intéresser à la détermination des différentes formes sous lesquelles cet élément peut être présent. Nous avons pour cela réalisé des extractions parallèles (spéciation de phases) du sélénium contenu dans les boues afin de déterminer quel pourcentage du sélénium total est réellement et potentiellement disponible pour les végétaux lors d'un épandage sur sol agricole. La spéciation d'espèces a été brièvement abordée dans le but de déterminer les teneurs en Se(IV) et Se(VI), espèces les plus toxiques.The great effort undertaken for about twenty years to improve the quality of surface waters has led to the construction of numerous waste water treatment plants, generating an increasing amount of sludge. Waste water and sludge treatment processes represent an important point in the hydrological cycle at which the disposal of substantial quantities of trace elements to the environment may be regulated. From the law on waste recovery and disposal in 1975 to the European guideline about wastes in 1991, the priority has been given to waste recovery and recycling. With increasing pressure to ban all sludge dumping at sea, and considering the prohibitive costs of land-filling and incineration, there is a great tendency to dispose of sludge on land (40% in 1988 to 60% in 1992).Although numerous studies have demonstrated the intrinsic value of sludge for soil amendment, given its nitrogen, phosphorus and homogeneous organic matter content, evidence has accumulated in recent years that numerous environmental problems can arise because of the presence in sludges of high amounts of certain trace elements (potentially toxic to plants and to human beings and liable to be concentrated along the food chain), among which selenium is particularly interesting.Selenium presents a complex case, as it is also an essential element for living organisms (including humans). The amendment with sewage sludge is sometimes used to increase the selenium content in crops, and afterwards in cattle, when there is a proven lack of this element in a given place. Nevertheless the boundary between essentiality and toxicity is relatively narrow and is expressed at trace levels. It is thus particularly important to survey the selenium concentrations encountered in sewage sludge, especially as guidelines and regulations concerning these data will probably be strengthened. Presently, in France, sludge must not contain more than 200 mg Se·kg-1 dry weight and must not be used on soils containing more than 10 mg Se·kg-1 dry weight (AFNOR U 44-041 norm). This norm concerns only the total amount of selenium contained in sludge and does not take into account the different species (organic and inorganic Se(-II), Se(0), Se(IV) and Se(VI)) that could be present.First of all we had to develop methods for the classical and microwave-assisted wet digestion of sewage sludge, and the determination of their total selenium concentration by Differential Pulse Cathodic Stripping Voltammetry (DPCSV) and ElectroThermal Atomic Absorption Spectrometry (ETAAS). Quality assurance involved the analysis of two BCR (Community Bureau of Reference) certified sewage sludge reference materials (CRM 145 R and CRM 007) and the different techniques were then applied to natural samples from a representative French sewage treatment plant located in the city of Tarbes (South-West of France). The mixture HNO3-H2O2-H2O led to the best results for the digestion and analysis of certified samples, caused few problems for the analysis by DPCSV and ETAAS, and was therefore retained. The decrease of the digestion duration obtained by the use of microwaves was particularly interesting (from one to three days on a hot plate to less than one hour by the Microdigest 301 (PROLABO, France)), and reproducibility was also acceptable (between 3 and 10%). Concentrations obtained for the sewage sludge from the Tarbes treatment plant were very much lower than those for NF U 44-041: 1.08±0.11 mg Se·kg-1 dry weight.However knowledge of speciation, that is to say the determination of the different physicochemical forms of selenium present in a given medium, is necessary when speaking of the toxicological risk represented by an element. The mobility of selenium and its toxicity to the biosphere are related to its association with various sludge or soil constituents as well as to its total concentration. "Soft" or partial extraction techniques are necessary when the aim of the study to determine trace element speciation. The extractants used must separate selenium from the matrix without inducing any loss or change in the partitioning of individual chemical species. In parallel extractions the mechanisms involved for each extractant must correspond to processes occurring in nature and are then associated with special fractions of selenium: soluble, exchangeable, "oxidizable", and "mineral" fractions .Parallel extractions with three types of extractants were chosen for this study and applied first to CRM 007: warm water (soluble fraction), ammonium phosphate-citric acid (soluble + exchangeable fraction) and sodium hydroxide (soluble + exchangeable + "oxidizable" fraction). The soluble, exchangeable, "oxidizable" and "mineral" fractions represent respectively : 11%, 14%, 39% and 36%. The same procedure was then applied to natural samples from Tarbes giving the following results: 36% soluble, 22% exchangeable, 42% "oxidizable". The sodium hydroxide extraction procedure allowed us to extract the entire Se content of this sludge (1.07±0.03 mg Se·kg-1 dry weight), showing that all the selenium present is potentially available after agricultural land application. It was then possible in this fraction to deal with the species speciation of selenium by the mean of a separation of inorganic and organic species on an Amberlite CG-400 resin and a specific analysis by DPCSV. Se(IV) and Se(VI) represent respectively between 30 and 40% and between 2 and 20% of total selenium in the sludges from Tarbes

Recipients of electric-powered indoor/outdoor wheelchairs provided by a National Health Service: A cross-sectional study

This is the post-print version of the final paper published in Archives of Physical Medicine and Rehabilitation. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2013 by the American Congress of Rehabilitation Medicine.OBJECTIVE: To describe the characteristics, across all ages, of powered wheelchair users and the assistive technology prescribed by a regional specialist wheelchair service DESIGN: Cross-sectional study SETTING: Regional wheelchair service provided to those fulfilling strict eligibility criteria by a National Health Service serving a population of 3 million. PARTICIPANTS: 544 Electric Powered Indoor/outdoor wheelchair (EPIOC) users. INTERVENTIONS: Not applicable MAIN OUTCOME MEASURES: Demographic, clinical/diagnostic details of EPIOC recipients including pain, (kypho)scoliosis and ventilators. Technical features including specialised (adaptive) seating (SS), tilt in space (TIS), and modified control systems. Factors were related to age groups: 1 (0-15), 2 (16-24), 3 (25-54), 4 (55-74) and 5 (75+). RESULTS: 262 men mean age 41.7 (range 8-82, sd 20.7) and 282 women mean age 47.2 (range 7-92, sd 19.7) years were studied. Neurological/neuromuscular conditions predominated (81%) with cerebral palsy (CP) (18.9%) and multiple sclerosis (16.4%). Conditions presenting at birth or during childhood constituted 39%. 99 had problematic pain, 83 a (kypho)scoliosis and 11 used ventilators. SS was provided to 169 users (31%), the majority had CP or muscular dystrophy. TIS was used by 258 (53%). Younger people were more likely to receive TIS than older ones. Only 92 had SS and TIS, mean age 29 (range 8-72, sd 17.8) years. 52 used modified control systems. CONCLUSIONS: The diversity of EPIOC users across age and diagnostic groups is shown. Their complex interrelationships with these technical features of EPIOC prescription are explored. Younger users were more complex due to age-related changes. This study provides outcomes of the EPIOC prescription for this heterogeneous group of very severely disabled people

Quizz en Infectiologie

National audienc

Replacement of animal models of cardiac arrest and resuscitation strategies using a computer simulation

This doctoral thesis explores cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) from a multidisciplinary perspective, with a focus on three main objectives: enhancing the Interdisciplinary Collaboration in Systems Medicine (ICSM) simulation suite, investigating the pathophysiology of CA, and proposing an alternative to animal models in CA and CPR research. The ICSM simulation suite was significantly improved, with additions such as a thoracic model for chest compressions, multiple organ tissue compartments, a vasculature equation accounting for resistance changes, circulatory transport delays, retrograded blood flow during CPR, and respiratory and cardiovascular control mechanisms. Utilizing the enhanced ICSM simulation suite, a series of studies were conducted to examine various aspects of CPR strategies, all with the aim of improving resuscitation outcomes. These studies encompassed investigations into the impact of positive end-expiratory pressure (PEEP) on cardiac output during CPR, the effects of chest compression rate, depth, and duty cycle, the influence of the precipitating aetiology on CPR strategy optimization, and the comparison of personalized CPR strategies to current guidelines. The research also quantitatively identified the effect of CPR parameters on cardiac output, with end compression force and positive end expiratory pressure emerging as significant contributors. The validation of the ICSM simulation suite thoracic model using individual haemodynamic recordings of a patient undergoing CPR demonstrated its capacity to simulate individualized patient data for retrospective identification of optimized CPR protocols. These outcomes collectively emphasize the potential of computational models, particularly the ICSM simulation suite, to revolutionize CA and CPR research by providing humane, informative, and personalized alternatives to traditional animal models. The findings of this research suggest that the ICSM simulation suite offers a valuable alternative to animal models in the study of CA and CPR. This computational model allows for the simulation and investigation of personalized CPR strategies, which can be tailored to individual patients' need

MODIFICAÇÃO DOS FATORES DE RISCO EM PACIENTES CADASTRADOS COM HIPERTENSÃO ARTERIAL NA ESF NOVA GUAIBA

Meu trabalho na ESF Nova Guaíba iniciou-se no início de março de 2016, começou com um processo de cadastramento na área. Primeiramente foi necessário me atualizar sobre os protocolos e as diferentes atendimentos em atenção primária à saúde, com um acompanhamento tecnológico que permitiu conhecer profundamente a realidade do sistema de saúde brasileiro. O formato do curso contribuiu para o processo ensino aprendizagem, o curso deu oportunidades para ampliar minha criatividade e capacidade de pensamento em outro contexto, muitas vezes requerendo análises críticas, pois as atividades exigiam analisar outras situações sociais e coletivas, assim como diferentes mudanças em relação a condutas, seguimento e tratamentos atualizados de pacientes com enfermidades crônicas, com ênfases em hipertensão arterial e diabetes mellitus e obesidade fundamentalmente. O principal objetivo foram mudanças em atendimentos em saúde de pacientes com enfermidades crônicas, hipertensos e diabéticos, muitos pacientes em triagem, chegavam com cifras exageradas de glicemia e tensão arterial, com tratamento errado e sem iniciar com abordagem em mudanças de estilo e modo de vida, por isso meu portfólio e trabalho final foi com intenção de contribuir e diminuir os fatores de risco em enfermidade hipertensiva, estes pacientes não tinham acompanhamento, já que não havia posto de saúde para acompanhar o paciente, foi então que se programou uma consulta domiciliar e consulta no posto a cada 3 meses. Este projeto de intervenção tem como objetivo trabalhar com pacientes cadastrados com Hipertensão arterial na ESF Nova Guaíba, com uma população cadastrada de 3900 pacientes permanentes e outros pacientes não permanentes. O município Guaíba tem escassos serviços de saúde como um ponto atendimento, e um centro de saúde da mulher e algumas referencia serviços médicos privados. A ESF Nova Guaíba – São Francisco têm uma equipe composta por uma enfermeira especialista em Saúde da Família, uma técnica de enfermagem/vacinadora e 6 agentes comunitários. A modificação de fatores de risco em enfermidade hipertensiva foi a proposta em projeto de intervenção e assim contribuir com modelos de promoção e prevenção de saúde mais adequados em aqueles pacientes que tenham risco de padecer doenças cardiovasculares, primeiramente elegemos um grupo de risco, sendo uma mostra alternativa de abordagem, utilizando como método de avaliação o estado nutricional e determinantes de fatores de risco, que serão informados mensalmente a partir do mês de abril, até agosto. Uma vez coletadas todas as informações em pesquisas e controles práticos dos dados educativo e nutricionais, elaborando-se o relatório final e apresentação dos resultados por equipe e comunidade. Com este trabalho pretendemos acompanhar os pacientes e melhorar sua qualidade de vida, para reduzir a morbimortalidade desta população de risco

Replacement of animal models of cardiac arrest and resuscitation strategies using a computer simulation

This doctoral thesis explores cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) from a multidisciplinary perspective, with a focus on three main objectives: enhancing the Interdisciplinary Collaboration in Systems Medicine (ICSM) simulation suite, investigating the pathophysiology of CA, and proposing an alternative to animal models in CA and CPR research. The ICSM simulation suite was significantly improved, with additions such as a thoracic model for chest compressions, multiple organ tissue compartments, a vasculature equation accounting for resistance changes, circulatory transport delays, retrograded blood flow during CPR, and respiratory and cardiovascular control mechanisms. Utilizing the enhanced ICSM simulation suite, a series of studies were conducted to examine various aspects of CPR strategies, all with the aim of improving resuscitation outcomes. These studies encompassed investigations into the impact of positive end-expiratory pressure (PEEP) on cardiac output during CPR, the effects of chest compression rate, depth, and duty cycle, the influence of the precipitating aetiology on CPR strategy optimization, and the comparison of personalized CPR strategies to current guidelines. The research also quantitatively identified the effect of CPR parameters on cardiac output, with end compression force and positive end expiratory pressure emerging as significant contributors. The validation of the ICSM simulation suite thoracic model using individual haemodynamic recordings of a patient undergoing CPR demonstrated its capacity to simulate individualized patient data for retrospective identification of optimized CPR protocols. These outcomes collectively emphasize the potential of computational models, particularly the ICSM simulation suite, to revolutionize CA and CPR research by providing humane, informative, and personalized alternatives to traditional animal models. The findings of this research suggest that the ICSM simulation suite offers a valuable alternative to animal models in the study of CA and CPR. This computational model allows for the simulation and investigation of personalized CPR strategies, which can be tailored to individual patients' need

Pain as a Symptom of Mental Health Conditions Among Undocumented Migrants in France: Results From a Cross-Sectional Study

ObjectivesThis study aimed to explore the associations between mental health status and experienced pain among undocumented migrants (UMs) in France.MethodsWe used data from the multicentric cross-sectional “Premier Pas” study conducted in the Parisian and Bordeaux regions from February to April 2019. Participants over 18 years of age were recruited from sixty-three sites. Pain was assessed through two variables: overall pain and musculoskeletal pain. Mental health conditions, including anxiety, sleep disorders, depression, and posttraumatic stress disorder (PTSD) were evaluated. Logistic regression models were used to explore associations, controlling for social determinants of health (SDHs).ResultsOur findings revealed significant associations between mental health status and pain among the 1,188 included participants. Sleep disorder was associated to higher odds of musculoskeletal pain (aOR = 2.53, 95% CI [1.20–5.33], p = 0.014). Stratified results indicated that among women, depression was associated to higher odds of pain (aOR = 4.85, 95% CI [1.53–13.36], p = 0.007).ConclusionThis large study confirms the connection between mental health status and pain among UMs, providing valuable evidence for clinicians to address mental health issues in this population

Infecção por VIH entre imigrantes na Guiana Francesa: alto risco durante os primeiros anos após a chegada

Introduction. Over 75% of HIV patients in French Guiana are foreigners most of whom are actually infected locally. Objectives. We aimed to estimate the distribution of infections in time after arrival using a retrospective cohort. Methods. CD4 erosion modelling allowed to estimate the date of infection which was compared to the date of arrival in French Guiana in the subset of foreign patients that were estimated to have acquired HIV locally. Results. Among patients estimated to have been infected in French Guiana and having arrived after 1999, over half had been infected within 4 years and that a quarter of patients had acquired HIV within the 2 first years after arrival (median 3.9 years IQR=2.1-7.8 years). Conclusions. The added value of the present results is to show the rapid infection dynamics after arrival and emphasize the necessity of increasingly proactive combined prevention in recently arrived immigrants.Introdução. Mais de 75% dos pacientes com HIV na Guiana Francesa são estrangeiros, a maioria dos quais estão realmente infectados localmente. Objetivos. O nosso objetivo era estimar a distribuição das infecções no tempo após a chegada, utilizando uma coorte retrospectiva. Métodos. A modelagem da erosão CD4 permitiu estimar a data da infecção que foi comparada à data de chegada na Guiana Francesa no subconjunto de pacientes estrangeiros que foram estimados como tendo adquirido o HIV localmente.Resultados. Entre os pacientes estimados como tendo sido infectados na Guiana Francesa e tendo chegado após 1999, mais da metade tinha sido infectada dentro de 4 anos e que um quarto dos pacientes tinha adquirido o HIV dentro dos 2 primeiros anos após a chegada (mediana de 3,9 anos IQR=2,1-7,8 anos). Conclusões. O valor agregado dos resultados atuais é mostrar a rápida dinâmica da infecção após a chegada e enfatizar a necessidade de uma prevenção combinada cada vez mais proativa nos imigrantes recém-chegados