An interactive meta-analysis of MRI biomarkers of myelin

Several MRI measures have been proposed as in vivo biomarkers of myelin, each with applications ranging from plasticity to pathology. Despite the availability of these myelin-sensitive modalities, specificity and sensitivity have been a matter of discussion. Debate about which MRI measure is the most suitable for quantifying myelin is still ongoing. In this study, we performed a systematic review of published quantitative validation studies to clarify how different these measures are when compared to the underlying histology. We analysed the results from 43 studies applying meta-analysis tools, controlling for study sample size and using interactive visualization (https://neurolibre.github.io/myelin-meta-analysis). We report the overall estimates and the prediction intervals for the coefficient of determination and find that MT and relaxometry-based measures exhibit the highest correlations with myelin content. We also show which measures are, and which measures are not statistically different regarding their relationship with histology

Comparative analysis of gait and speech in Parkinson's disease: hypokinetic or dysrhythmic disorders?

International audienceGait and speech are automatic motor activities which are frequently impaired in Parkinson's disease (PD). Obvious clinical similarities exist between these disorders but were never investigated. We propose to determine whether there exist any common features in PD between spatiotemporal gait disorders and temporal speech disorders. Gait and speech were analyzed on eleven PP undergoing deep-brain-stimulation of the sub-thalamic-nucleus (STN-DBS) and eleven control subjects (CS) under 3 conditions of velocity (natural, slow and speed). The patients were tested with and without L-Dopa and stimulator ON or OFF. Locomotor parameters were recorded using an optoelectronic system. Speech parameters were recorded with a headphone while subjects were reading a short paragraph. The results confirmed that PP walk and read more slowly than controls. Patient's difficulties in modulating walking and speech velocities seem to be due mainly to an inability to internally control the step length and the interpause-speech duration ISD. STN-DBS and levodopa increased patients' walking velocity by increasing the step length. STN-DBS and levodopa had no effect on speech velocity but restored the patients' ability to modulate the ISD. The walking cadence and speech index of rythmicity (SPIR) tended to be lower in patients and were not significantly improved by STN-DBS or levodopa. Speech and walking velocity as well as ISD and step length were correlated in both groups. Negative correlations between SPIR and walking cadence were observed in both groups Similar fundamental hypokinetic impairment and probably a similar rhythmic factor affected similarly the patients' speech and gait. These results suggest a similar physiopathological process in both walking and speaking dysfunction

New treatment options for lupus – a focus on belimumab

Belimumab is the first biologic approved for patients with systemic lupus erythematosus (SLE). Belimumab is the first of a new class of drug targeting B cell-stimulating factors or their receptors to reach the market. Its target, BLyS, also known as BAFF (B cell-activating factor from the tumor necrosis factor family), is a type II transmembrane protein that exists in both membrane-bound and soluble forms. Additionally to a robust rational from murine experiments conducted in lupus prone mice, BLyS circulating levels are increased in SLE patients. After the negative results of a Phase II trial, two Phase III trials met their primary endpoints. Some SLE patients are still refractory to the standard options of care or necessitate prolonged high-dose corticotherapy and/or long-term immunosuppressive regimens. However, some experts still feel that the effect of this biologic might not be clinically relevant and blame the use of the new systemic lupus response index as well as the discrepancies between both trials and the noninclusion of the severe form of the disease as nephritis. In this review, we aim to discuss the characteristics of belimumab, critically evaluate the different steps of its development, and consider its future place in the arsenal against SLE, taking into account the patients’ perspectives

Antioxidant Potential is Correlated to ω6 / ω3 Ratio and Brasfield Score in Cystic Fibrosis Children

International audienceOBJECTIVES:Oxidative stress is associated with the condition of cystic fibrosis (CF), but no guidelines exist for its assessment or treatment. Our aim was to evaluate a test that measures the blood antioxidant capability in CF children.METHODS:This antioxidant capability was assessed by the Kit Radicaux Libres (KRL) test in 44 CF children (24 boys). We recorded also anthropometric measures, pulmonary function, CF severity scores, and plasma nutritional and inflammatory parameters (proteins, vitamins, erythrocyte fatty acids, and micronutrients). We performed univariate and multivariate analyses with linear regression models.RESULTS:The mean age at the first KRL assessment was 12.2 ± 3.8 years. Factors that correlated with decreased antioxidant capacity were mostly related to the severity of pulmonary disease [ forced expiratory volume at 1 second (FEV1), acute exacerbation, and congestion. In multivariate analysis, the correlation between Brasfield score and erythrocyte antioxidant potential remained significant (β = - 0.611, p < 0.001). Among nutritional factors, the ω6/ω3 ratio was significantly correlated to erythrocyte antioxidant potential (β = - 1.213, p = 0.01).CONCLUSION:The blood antioxidant capability, measured by the KRL test, appears to be an interesting biomarker to evaluate oxidative stress in CF. This study suggests that the ω6/ω3 ratio should be regarded as a nutritional marker in antioxidant management in CF children

Enhancement of Aedes aegypti susceptibility to dengue by Wolbachia is not supported

No abstract available

Beating quantum limits in interferometers with quantum locking of mirrors

The sensitivity in interferometric measurements such as gravitational-wave detectors is ultimately limited by quantum noise of light. We discuss the use of feedback mechanisms to reduce the quantum effects of radiation pressure. Recent experiments have shown that it is possible to reduce the thermal motion of a mirror by cold damping. The mirror motion is measured with an optomechanical sensor based on a high-finesse cavity, and reduced by a feedback loop. We show that this technique can be extended to lock the mirror at the quantum level. In gravitational-waves interferometers with Fabry-Perot cavities in each arms, it is even possible to use a single feedback mechanism to lock one cavity mirror on the other. This quantum locking greatly improves the sensitivity of the interferometric measurement. It is furthermore insensitive to imperfections such as losses in the interferometer

Risk Factors of Inadequate Colposcopy After Large Loop Excision of the Transformation Zone: A Prospective Cohort Study

International audienceObjective: The aim of the study was to identify the risk factors of post-large loop excision of the transformation zone (LLETZ) inadequate colposcopy. Materials and Methods: From December 2013 to July 2014, a total of 157 patients who had a LLETZ performed for the treatment of high-grade intraepithelial lesion with fully visible cervical squamocolumnar junction were included. All procedures were performed using semicircular loops. The use of colposcopy made during each procedure was systematically documented. Dimensions and volume of LLETZ specimens were measured at the time of procedure, before formaldehyde fixation. All participants were invited for a follow-up colposcopy 3 to 6 months after LLETZ. Primary end point was the diagnosis of post-LLETZ inadequate colposcopy, defined by a not fully visible cervical squamocolumnar junction and/or cervical stenosis. Results: Colposcopies were performed in a mean (SD) delay of 136 (88) days and were inadequate in 22 (14%) cases. Factors found to significantly increase the probability of post-LLETZ inadequate colposcopy were a history of previous excisional cervical therapy [adjusted odds ratio (aOR) = 4.29, 95% CI = 1.12-16.37, p = .033] and the thickness of the specimen (aOR = 3.12, 95% CI = 1.02-9.60, p = .047). The use of colpos-copy for the guidance of LLETZ was statistically associated with a decrease in the risk of post-LLETZ inadequate colposcopy (aOR = 0.19, 95% CI = 0.04-0.80, p = .024) as the achievement of negative endocervical margins (aOR = 0.26, 95% CI = 0.08-0.86, p = .027). Conclusions: Although the risk of post-LLETZ inadequate colpos-copy is increased in patients with history of excisional therapy and with the thickness of the excised specimen, it could be reduced with the use of colposcopic guidance and the achievement of negative endocervical margins. L arge loop excision of the transformation zone (LLETZ) is a routine procedure worldwide, because it is the first-line treatment of high-grade intraepithelial lesion (HSIL) of the cervix. Quality criteria for optimal LLETZ include the completeness of excision with the achievement of negative margins, while producing the minimal excised volume and depth of excision to minimize subsequent obstetrical and neonatal morbidity. 1,2 Obtaining negative margins is important, because incomplete excision exposes women to a significant risk of posttreatment residual and/or recurrent disease, particularly when the lesion involves the endo-cervical canal. 3,4 However, this risk remains higher to the general female population, even when negative margins are achieved. Women who had had a LLETZ remain therefore exposed to a 3-to 4-fold increased risk of developing subsequent cervical cancer at least for 20 years. 5-8 Thus, prolonged and careful post-LLETZ follow-up is mandatory, whatsoever the margins status. For the last decade, the value of human papillomavirus testing has been demonstrated in this indication. Although a negative human papillomavirus test has now been admitted as the best test of cure for patients, colposcopy remains needed when this test is found to be positive. 9-12 Although being the key examination in this indication, the accuracy of colposcopy performed after previous excisional therapy of HSIL is however questionable because the healing process might result in changes in the appearance of the transformation zone (TZ). However, the main limitation of post-LLETZ colposcopic examination is the possibility of inadequate colposcopy due to the inability to visualize the entire TZ. Known risk factors for inadequate colposcopy include age, severity of lesion, and estrogen status of the patient. 13 However, inadequate colposcopy is also one of the main adverse effects of excisional therapies of the cervix, including LLETZ. 13 However, data on the precise risk factors for inadequate colposcopy after LLETZ are limited because most studies have focused on the sole risk of cervical stenosis without considering the position and visibility of the squamocolumnar junction. 14-17 This point is however crucial because it is clinically essential to identify how post-LLETZ inadequate colposcopy could be avoided, thus preserving the possibility for the follow-up of these women

The HLS19-COM-P, a New Instrument for Measuring Communicative Health Literacy in Interaction with Physicians: Development and Validation in Nine European Countries

Background: Sufficient communicative health literacy (COM-HL) is important for patients actively participating in dialogue with physicians, expressing their needs and desires for treatment, and asking clarifying questions. There is a lack of instruments combining communication and HL proficiency. Hence, the aim was to establish an instrument with sufficient psychometric properties for measuring COM-HL. Methods: The HLS19-COM-P instrument was developed based on a conceptual framework integrating HL with central communicative tasks. Data were collected using different data collection modes in nine countries from December 2019 to January 2021 (n = 18,674). Psychometric properties were assessed using Rasch analysis and confirmatory factor analysis. Cronbach’s alpha and Person separation index were considered for reliability. Results: The 11-item version (HLS19-COM-P-Q11) and its short version of six items (HLS19-COM-P-Q6) fit sufficiently the unidimensional partial credit Rasch model, obtained acceptable goodness-of-fit indices and high reliability. Two items tend to under-discriminate. Few items displayed differential item functioning (DIF) across person factors, and there was no consistent pattern in DIF across countries. All items had ordered response categories. Conclusions: The HLS19-COM-P instrument was well accepted in nine countries, in different data collection modes, and could be used to measure COM-HL.publishedVersio

039: Platelet reactivity predicts both ischemic and bleeding events at one year follow-up in acute coronary syndome patients receiving prasugrel

There are evidences of a link between platelet reactivity inhibition and thrombotic and bleeding events. We have previously demonstrated that PR after prasugrel loading dose (LD) predicts short-term thrombotic events. We aimed to further investigate the relationship between PR under prasugrel and one-year thrombotic and bleeding events.MethodPatients were prospectively included in this multicentre study if they had a successful PCI for an acute coronary syndrome (ACS) and received prasugrel. Vasodilator-Stimulated Phosphoprotein (VASP index) was measured after prasugrel LD. Endpoint included the rate of thrombotic events (cardiovascular death, myocardial infarction and stent thrombosis) and bleeding events (TIMI) at one year.ResultsThree hundreds and one patients were enrolled. Nine patients (3%) were lost to follow-up at one year. The rates of thrombotic and bleeding events at one year were 7.5 and 6.8% respectively. The mean VASP index after a 60mg LD of prasugrel was 34}23% and 76 patients (25%) were considered as having high on-treatment platelet reactivity (HTPR). Patients with HTPR had a higher rate of thrombotic events compared to good responders (19.7 vs 3.1%;p<0.001). Patients with a minor or major non-CABG related TIMI bleeding had lower PR compared to patients with no bleeding events (21}18 vs 35}23%;p=0.008). In multivariate analysis, the VASP index predicted both thrombotic and bleeding events (OR: 1.44 (95% CI: 1.2–1.72; p<0.001 and 0.75 (95% CI: 0.59–0.96;p=0.024 (respectively, per 10% increase)).ConclusionPlatelet reactivity measurement after prasugrel LD predicts both ischemic and bleedings events at one year follow-up for ACS patients undergoing PCI