Prévention de la syncope chez l'homme

- Cette étude propose d'améliorer les valeurs de sensibilité et de spécificité d'un test médical de diagnostic de la syncope chez l'homme. Cette amélioration repose notamment sur l'utilisation d'un réseau de neurones

Predictors of Walking impairment in Patients With Claudication Using Linear & Non-Linear Models

Objective: To identify new variables associated to maximal walking time on treadmill (MWT) in patients with claudication. Material: We retrospectively analysed data of 1120 patients referred for transcutaneous exercise oxymetry (TcpO2). Methods: The outcome measurement was the absolute walking time (MWT) on treadmill (3.2 km/h, 10% slope). We used linear regression analyses (LRA) and a non-linear analysis (NLA) combining Support Vector Machines and Genetic Explanatory in 800 patients with the following resting variables: Age, gender, body mass index (BMI), the presence of diabetes (Db), minimal ankle to brachial index at rest (ABI), usual walking speed over 10 m (WS10), Number of comorbid conditions (CMC), smoking behaviour (Smo), resting heart rate (HR), pre-test glycemia (Gly) and haemoglobin (Hg), beta-blocker use (BB), and exercise-derived variables: minimal value of pulse oxymetry (Sat), resting chest tcpO2 (TcpO2-rest), decrease in chest tcpO2 during exercise (DCT), presence of buttock ischemia defined as a DROP index < -15 mmHg (Butt-I). Results: Independent variables associated to MWT, by decreasing importance in the models, were : ABI, Age, BMI, WS10m, DC-TcpO2, Smo, Butt-I, Gly, HR for the NLA, and Age, ABI, WS10; TcpO2-rest, BMI, Smo, Butt-I, HR and BB for the LRA (r=0.518; p<0.01). Gender, Db, CMC, Hb, Gly and Sat were not detected as significantly associated to MWT on treadmill with the LNA and LRA models. Testing of models against MWT over 320 new patients gave r=0.509 for LRA and 0.575 for NLA (both p<0.05). Conclusions: In addition to ABI, Age, BMI and Smo were found new variables associated to MWT : Butt-I, HR and WS10

Analysis of three statistical methods to predict the presence of carotid atheromatous plaques

Background: At least 15-20% of all ischemic strokes are attributable to atherosclerosis [1]. We analyzed three statistical methods for 12 traditional risk factors (TRF) i.e. age, sex, arterial pressure, Intima Media Tickness (IMT), Pulse Wave Velocity (PWV) in order to predict the presence of carotid atherosclerotic plaques. Methods: We studied 48 patients (27 men, mean age 52+/-10.9) after a vascular screening for atherosclerosis from a metabolic syndrome cohort in a retrospective way. Fourteen patients presented carotid atheromatous plaques confirmed by a trained operator using an ultrasound system. The sensitivity and specificity of the combination of the IMT and the PWV indices with other risk factors were considered using: multiple linear regressions (MLR), support vector machines (SVM) [2] and discriminant analysis (DA). The best combinations of variables were kept for each learning machine. Results: The best sensibility and specificity were obtained using DA. This method reached a sensitivity of 95+/-7% and a specificity of 73+/-36% with an area under the ROC curve equal to 0.84+/-0.35. The other methods showed a sensitivity of 73+/-13% for the MLR method and 53+/-34% for the SVM method with an area under the ROC curve of 0.72+/-0.07 and 0.74+/-0.18 respectively. Conclusion: This preliminary study shows that carotid atherosclerotic plaques could be reliably predicted using discriminant analysis method. Additional studies are needed to confirm the statistical differences observed using this method and to predict the severity of carotid atherosclerosis

Identification of new factors associated to walking impairment in patients with vascular-type claudication

OBJECTIVES: Mechanisms of walking limitation in arterial claudication are incompletely elucidated. We aimed to identify new variables associated to walking limitation in patients with claudication. METHODS: We retrospectively analyzed data of 1120 patients referred for transcutaneous exercise oxygen pressure recordings (TcpO). The outcome measurement was the absolute walking time on treadmill (3.2 km/h, 10% slope). We used both: linear regression analysis and a non-linear analysis, combining support vector machines and genetic explanatory in 800 patients with the following resting variables: age, gender, body mass index, the presence of diabetes, minimal ankle to brachial index at rest, usual walking speed over 10 m (usual-pace), number of comorbid conditions, active smoking, resting heart rate, pre-test glycaemia and hemoglobin, beta-blocker use, and exercise-derived variables: minimal value of pulse oximetry, resting chest-TcpO, decrease in chest TcpO during exercise, presence of buttock ischemia defined as a decrease from rest of oxygen pressure index ≤15 mmHg. We tested the models over 320 other patients. RESULTS: Independent variables associated to walking time, by decreasing importance in the models, were: age, ankle to brachial index, usual-pace; resting TcpO, body mass index, smoking, buttock ischemia, heart rate and beta-blockers for the linear regression analysis, and were ankle to brachial index, age, body mass index, usual-pace, decrease in chest TcpO, smoking, buttock ischemia, glycaemia, heart rate for the non-linear analysis. Testing of models over 320 new patients gave r = 0.509 for linear and 0.575 for non-linear analysis (both p < 0.05). CONCLUSION: Buttock ischemia, heart rate and usual-pace are new variables associated to walking time

Automatic Detector of Abnormal EEG for Preterm Infants

Many of preterm babies suffer from neural disorders caused by birth complications. Hence, early prediction of neural disorders, in preterm infants, is extremely crucial for neuroprotective intervention. In this scope, the goal of this research was to propose an automatic way to study preterm babies Electroencephalograms (EEG). EEG were preprocessed and a time series of standard deviation was computed. These series were thresholded to detect Inter Burst Intervals (IBI). Features were extracted from bursts and IBI and were then classified as Abnormal or Normal using a Multiple Linear Regression. The method was successfully validated on a corpus of 100 infants with no early indication of brain injury. It was also implemented with a user-friendly interface using Java

Making America A Better Place for All: Sustainable Development Recommendations for the Biden Administration

In 2015, the United Nations Member States, including the United States, unanimously approved 17 Sustainable Development Goals (SDGs) to be achieved by 2030. The SDGs are nonbinding; each nation is to implement them based on its own priorities and circumstances. This Article argues that the SDGs are a critical normative framework the United States should use to improve human quality of life, freedom, and opportunity by integrating economic and social development with environmental protection. It collects the recommendations of 22 experts on steps that the Biden-Harris Administration should take now to advance each of the SDGs. It is part of a book project that will recommend not only federal actions, but also actions by state and local governments, the private sector, and civil society. In the face of multiple challenges and opportunities, this Article is intended to contribute to a robust public discussion about how to accelerate the transition to a sustainable society and make America a better place for all

A uniform procedure for the purification of CDK7/CycH/MAT1, CDK8/CycC and CDK9/CycT1

We have established a uniform procedure for the expression and purification of the cyclin-dependent kinases CDK7/CycH/MAT1, CDK8/CycC and CDK9/CycT1. We attach a His(6)-tag to one of the subunits of each complex and then co-express it together with the other subunits in Spodoptera frugiperda insect cells. The CDK complexes are subsequently purified by Ni(2+)-NTA and Mono S chromatography. This approach generates large amounts of active recombinant kinases that are devoid of contaminating kinase activities. Importantly, the properties of these recombinant kinases are similar to their natural counterparts (Pinhero et al. 2004, Eur J Biochem 271:1004-14). Our protocol provides a novel systematic approach for the purification of these three (and possibly other) recombinant CDKs

Loss of the Wnt/β-catenin pathway in microglia of the developing brain drives pro-inflammatory activation leading to white matter injury

Microglia-mediated neuroinflammation is key in numerous brain diseases including encephalopathy of the preterm born infant. Microglia of the still-developing brain have unique properties but little is known of how they regulate their inflammatory activation. This is important information as every year 9 million preterm born infants acquire persisting neurological injuries associated with encephalopathy and we lack strategies to prevent and treat these injuries. Our study of activation state regulators in immature brain microglia found a robust down-regulation of Wnt/β-catenin pathway receptors, ligands and intracellular signalling members in pro-inflammatory microglia. We undertook our studies initially in a mouse model of microglia-mediated encephalopathy including the clinical hallmarks of oligodendrocyte injury and hypomyelination. We purified microglia from this model and applied a genome-wide transcriptomics analysis validated with quantitative profiling. We then verified that down-regulation of the Wnt/β-catenin signalling cascade is sufficient and necessary to drive microglia into an oligodendrocyte-damaging phenotype using multiple pharmacological and genetic approaches in vitro and in vivo in mice and in humans and zebrafish. We also demonstrated that genomic variance in the WNT/β-catenin pathway is associated with the anatomical connectivity phenotype of the human preterm born infant. This integrated analysis of genomics and connectivity, as a surrogate for oligodendrocyte function/myelination, is agnostic to cell type. However, this data indicates that the WNT pathway is relevant to human brain injury and specifically that WNT variants may be useful clinically for injury stratification and prognosis. Finally, we performed a translational experiment using a BBB penetrant microglia-specific targeting 3DNA nanocarrier to deliver a Wnt agonist specifically and directly to microglia in vivo. Increasing the activity of the Wnt/β-catenin pathway specifically in microglia in our model of microglia-mediated encephalopathy was able to reduce microglial pro-inflammatory activation, prevent the typical hypomyelination and also prevent the long-term memory deficit associated with this hypomyelination. In summary, the canonical Wnt/β-catenin pathway regulates microglial activation and up-regulation of this pathway could be a viable neurotherapeutic strategy

Dimethyl sulfoxide blocks herpes simplex virus-1 productive infection in vitro acting at different stages with positive cooperativity. Application of micro-array analysis

BACKGROUND: Dimethyl sulfoxide (DMSO) is frequently used at a concentration of up to 95% in the formulation of antiherpetic agents because of its properties as a skin penetration enhancer. Here, we have analyzed the effect of DMSO on several parameters of Herpes Simplex Virus replication. METHODS: Productive infection levels of HSV-1 were determined by plaque assay or by reporter gene activity, and its DNA replication was estimated by PCR. Transcript levels were evaluated with HSV-specific DNA micro-arrays. RESULTS: DMSO blocks productive infection in vitro in different cell types with a 50% inhibitory concentration (IC(50)) from 0.7 to 2% depending upon the multiplicity of infection. The concentration dependence exhibits a Hill coefficient greater than 1, indicating that DMSO blocks productive infection by acting at multiple different points (mechanisms of action) with positive cooperativity. Consistently, we identified at least three distinct temporal target mechanisms for inhibition of virus growth by DMSO. At late stages of infection, DMSO reduces virion infectivity, and markedly inhibits viral DNA replication. A third mode of action was revealed using an oligonucleotide-based DNA microarray system for HSV. These experiments showed that DMSO reduced the transcript levels of many HSV-1 genes; including several genes coding for proteins involved in forming and assembling the virion. Also, DMSO markedly inhibited some but not all early transcripts indicating a previously unknown mode for inhibiting the early phase of HSV transcription-replication cycle. CONCLUSION: These observations suggest that DMSO itself may have a role in the anti-herpetic activity of formulations utilizing it as a dispersant