RESUMO
BACKGROUND: In January 2016, the French Medicine Agency initiated a Temporary Recommendation for Use (TRU) to allow the use of oral intake of tenofovir disoproxil fumarate and emtricitabine for pre-exposure prophylaxis (PrEP) in adults at high risk of HIV. We report the results of the first year of PrEP implementation in France. METHODS: Data were collected by physicians using a secured web subject-monitoring interface, with two forms: an initiation form, with patients' baseline characteristics, and an HIV seroconversion form. Univariate and adjusted multivariate analysis using a logistic regression model were performed to identify baseline factors associated with on-demand PrEP regimen prescription. RESULTS: From 4 January 2016 to 28 February 2017, 3405 subjects were enrolled, with 2774 initiation forms completed; 98.1% were male and 96.9% were MSM. An on-demand regimen was prescribed to 57% of subjects. Older age (OR for participants older than 50 yearsâ=â1.76, 95% CI 1.35-2.3, Pâ<â0.001) and site of prescription (OR of former IPERGAY sitesâ=â2.28, 95% CI 1.84-2.83, Pâ<â0.001) were associated with on-demand prescription. Those reporting sexually transmitted infection (STI) and condomless anal sex with at least two different partners were less likely to receive on-demand PrEP (ORâ=â0.68, 95% CI 0.57-0.82 and 0.75, 95% CI 0.57-0.98, respectively; Pâ<â0.05 for all). Four breakthrough HIV infections were reported during the study, in the context of PrEP interruption or acute infection at the time of PrEP initiation. CONCLUSIONS: In a real-life setting in France, PrEP was used, either daily or on-demand, mostly by MSM, with breakthrough infections being rare.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Emtricitabina/administração & dosagem , Infecções por HIV/prevenção & controle , Implementação de Plano de Saúde , Profilaxia Pré-Exposição , Tenofovir/administração & dosagem , Adulto , Comorbidade , Feminino , França/epidemiologia , Infecções por HIV/epidemiologia , Homossexualidade Masculina , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Avaliação de Resultados em Cuidados de Saúde , Profilaxia Pré-Exposição/métodos , Sexo sem ProteçãoRESUMO
OBJECTIVES: Our work was aimed to evaluate Alzheimer's disease diagnosis improvement using cerebrospinal fluid biomarkers (CSF) in neurological daily practice. MATERIALS AND METHODS: For this purpose, 150 patients clinically and neurochemically classified as having AD or cognitive impairment with or without other dementia type were included in the study. The following CSF peptides were studied, blindly to the clinical diagnosis: beta-amyloid(1-42) peptide (Aß(1-42)), Tau (T-tau), threonine-181 hyperphosphorylated tau protein (P-tau(181)), and beta-amyloid(1-40) peptide (Aß(1-40)). From these measurements, Innotest® Amyloid Tau Index (IATI) was calculated for each patient. RESULTS: This assessment allowed to separate 83 biochemical profiles of AD and 67 non-Alzheimer's disease (non-AD), both AD and non-AD categories match with clinical data amounting to 73% and 90%, respectively. Among mild cognitive impairment (MCI) patients, CSF biomarkers led to discriminate those who are likely to be AD. We devoted a special section to Aß(1-40) which is not a routine parameter but can help to confirm a pathological amyloid process as Aß(1-42)/Aß(1-40) ratio underlining the real decline of the Aß(1-42). CONCLUSIONS: The interest of biomarkers and their ability to solve awkward cases were carefully noticed all the more when a discrepancy between clinical and CSF biological data was involved. The final proposed algorithm allowed to identify pathogenic forms of AD according to the prevailing role of hyperphosphorylated tau or amyloid beta peptide.
Assuntos
Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/líquido cefalorraquidiano , Disfunção Cognitiva/líquido cefalorraquidiano , Disfunção Cognitiva/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas tau/líquido cefalorraquidianoRESUMO
After a complete spinal section, quadruped mammals (cats, rats, and mice) can generally regain hindlimb locomotion on a treadmill because the spinal cord below the lesion can express locomotion through a neural circuitry termed the central pattern generator (CPG). In this review, we propose that the spinal CPG also plays a crucial role in the locomotor recovery after incomplete spinal cord injury.
Assuntos
Locomoção/fisiologia , Traumatismos da Medula Espinal/fisiopatologia , Adaptação Fisiológica , Animais , Gatos , Modelos Animais de Doenças , Humanos , Instinto , Camundongos , Regeneração Nervosa/fisiologia , Vias Neurais/fisiologia , RatosRESUMO
The restless legs syndrome (RLS) is one of the commonest neurological sensorimotor disorders at least in the Western countries and is often associated with periodic limb movements (PLM) during sleep leading to severe insomnia. However, it remains largely underdiagnosed and its underlying pathogenesis is presently unknown. Women are more affected than men and early-onset disease is associated with familial cases. A genetic origin has been suggested but the mode of inheritance is unknown. Secondary causes of RLS may share a common underlying pathophysiology implicating iron deficiency or misuse. The excellent response to dopaminegic drugs points to a central role of dopamine in the pathophysiology of RLS. Iron may also represent a primary factor in the development of RLS, as suggested by recent pathological and brain imaging studies. However, the way dopamine and iron, and probably other compounds, interact to generate the circadian pattern in the occurrence of RLS and PLM symptoms remains unknown. The same is also the case for the level of interaction of the two compounds within the central nervous system (CNS). Recent electrophysiological and animals studies suggest that complex spinal mechanisms are involved in the generation of RLS and PLM symptomatology. Dopamine modulation of spinal reflexes through dopamine D3 receptors was recently highlighted in animal models. The present review suggests that RLS is a complex disorder that may result from a complex dysfunction of interacting neuronal networks at one or several levels of the CNS and involving numerous neurotransmitter systems.
Assuntos
Síndrome das Pernas Inquietas , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/fisiopatologia , Ritmo Circadiano/fisiologia , Modelos Animais de Doenças , Dopamina/metabolismo , Humanos , Ferro/metabolismo , Entorpecentes/metabolismo , Síndrome das Pernas Inquietas/epidemiologia , Síndrome das Pernas Inquietas/genética , Síndrome das Pernas Inquietas/fisiopatologiaRESUMO
Oxidative stress results from the imbalance between reactive oxygen species (ROS) and ROS-scavenging molecules. Among them, cytosolic glutathione peroxidase (GPX1) plays a major role as it reduces a large part of intracellular ROS. Endothelial cells are a barrier for potentially aggressive molecules circulating in the blood stream and, therefore, are often under great oxidative stress. Thus, we investigated the potentially protective effects of GPX1 overexpression in the endothelial cell line, ECV304. We found that chronic GPX1 overexpression delays cell growth without affecting viability or decreasing resistance to hydrogen peroxide-induced oxidative stress. As GPX1 overexpression could drain the cellular reduced glutathione (GSH) pool, we also tested the effects of extracellular GSH supplementation on cell growth. Despite its largely referenced beneficial effects for cells, GSH was toxic for ECV304 cells in a dose-dependent manner but GSH-induced toxicity was reduced in selenium supplemented cultures and completely abolished in ECV304 overexpressing GPX1, compared to control. In summary, GPX1 overexpression delays cell growth and protects them from GSH and H(2)O(2) toxicity.