Classifying Idiopathic Rapid Eye Movement Sleep Behavior Disorder, Controls, and Mild Parkinson\u27s Disease Using Gait Parameters

Background Subtle gait changes associated with idiopathic rapid eye movement sleep behavior disorder (iRBD) could allow early detection of subjects with future synucleinopathies. Objective The aim of this study was to create a multiclass model, using statistical learning from probability distribution of gait parameters, to distinguish between patients with iRBD, healthy control subjects (HCs), and patients with Parkinson\u27s disease (PD). Methods Gait parameters were collected in 21 participants with iRBD, 21 with PD, and 21 HCs, matched for age, sex, and education level. Lasso sparse linear regression explored gait features able to classify the three groups. Results The final model classified iRBD from HCs and from patients with PD equally well, with 95% accuracy, 100% sensitivity, and 90% specificity. Conclusions Gait parameters and a pretrained statistical model can robustly distinguish participants with iRBD from HCs and patients with PD. This could be used to screen subjects with future synucleinopathies in the general population and to identify a conversion threshold to PD. © 2022 International Parkinson and Movement Disorder Societ

BeatWalk: Personalized Music-Based Gait Rehabilitation in Parkinson’s Disease

Taking regular walks when living with Parkinson’s disease (PD) has beneficial effects on movement and quality of life. Yet, patients usually show reduced physical activity compared to healthy older adults. Using auditory stimulation such as music can facilitate walking but patients vary significantly in their response. An individualized approach adapting musical tempo to patients’ gait cadence, and capitalizing on these individual differences, is likely to provide a rewarding experience, increasing motivation for walk-in PD. We aim to evaluate the observance, safety, tolerance, usability, and enjoyment of a new smartphone application. It was coupled with wearable sensors (BeatWalk) and delivered individualized musical stimulation for gait auto-rehabilitation at home. Forty-five patients with PD underwent a 1-month, outdoor, uncontrolled gait rehabilitation program, using the BeatWalk application (30 min/day, 5 days/week). The music tempo was being aligned in real-time to patients’ gait cadence in a way that could foster an increase up to +10% of their spontaneous cadence. Open-label evaluation was based on BeatWalk use measures, questionnaires, and a six-minute walk test. Patients used the application 78.8% (±28.2) of the prescribed duration and enjoyed it throughout the program. The application was considered “easy to use” by 75% of the patients. Pain, fatigue, and falls did not increase. Fear of falling decreased and quality of life improved. After the program, patients improved their gait parameters in the six-minute walk test without musical stimulation. BeatWalk is an easy to use, safe, and enjoyable musical application for individualized gait rehabilitation in PD. It increases “walk for exercise” duration thanks to high observance.This research was supported by a European grant: BeatHealth: Health and Wellness on the Beat for VC, DD, CL, AGi, VD, RV, EH, ED, ML, BB, and SB (EU FP7-ICT contract #610633)

CBP-HSF2 structural and functional interplay in Rubinstein-Taybi neurodevelopmental disorder

Rubinstein-Taybi syndrome (RSTS) is a neurodevelopmental disorder with unclear underlying mechanisms. Here, the authors unravel the contribution of a stress-responsive pathway to RSTS where impaired HSF2 acetylation, due to RSTS-associated CBP/EP300 mutations, alters the expression of neurodevelopmental players, in keeping with hallmarks of cell-cell adhesion defects.Patients carrying autosomal dominant mutations in the histone/lysine acetyl transferases CBP or EP300 develop a neurodevelopmental disorder: Rubinstein-Taybi syndrome (RSTS). The biological pathways underlying these neurodevelopmental defects remain elusive. Here, we unravel the contribution of a stress-responsive pathway to RSTS. We characterize the structural and functional interaction between CBP/EP300 and heat-shock factor 2 (HSF2), a tuner of brain cortical development and major player in prenatal stress responses in the neocortex: CBP/EP300 acetylates HSF2, leading to the stabilization of the HSF2 protein. Consequently, RSTS patient-derived primary cells show decreased levels of HSF2 and HSF2-dependent alteration in their repertoire of molecular chaperones and stress response. Moreover, we unravel a CBP/EP300-HSF2-N-cadherin cascade that is also active in neurodevelopmental contexts, and show that its deregulation disturbs neuroepithelial integrity in 2D and 3D organoid models of cerebral development, generated from RSTS patient-derived iPSC cells, providing a molecular reading key for this complex pathology.</p

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Efficacy and tolerance of botulinum toxin injections after sacral nerve stimulation failure for idiopathic overactive bladder

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Effectiveness and Safety of an Intracameral Injection of Cefuroxime for the Prevention of Endophthalmitis After Cataract Surgery With or Without Perioperative Capsular Rupture

International audienceIMPORTANCE:Postoperative endophthalmitis (POE) often results in severe visual impairment. In clinical studies, an intracameral cefuroxime injection at the end of surgery was found to be effective at reducing the incidence of POE. Two important issues are the retinal safety of cefuroxime and its use for patients with perioperative capsular rupture where the risk of POE is dramatically increased.OBJECTIVE:To assess the effectiveness and retinal safety of an intracameral injection of cefuroxime sodium for the prevention of POE and its possible use in cases of a perioperative capsular rupture of the lens.DESIGN, SETTING, AND PARTICIPANTS:Population-based cohort study of patients 40 years of age or older who underwent cataract surgery at 1 of 1546 French health care facilities, public or private, and whose medical records were obtained from the national administrative database. Data analyses were performed between March and November 2015.MAIN OUTCOMES AND MEASURES:The effectiveness and safety of the prophylactic injection of cefuroxime as measured by the incidence of POE and cystoid macular edema.RESULTS:From January 2010 to October 2014, a total of 3 351 401 eyes of 2 434 008 patients 40 years of age or older (58.9% were women, and the mean [SD] age was 73.9 [9.5] years) underwent cataract surgery; 1941 patients (0.08%) developed POE during the 6 weeks after cataract surgery. The incidence of POE after cataract surgery decreased over the course of the study (0.11%, 0.09%, 0.08%, 0.06%, and 0.05% in 2010, 2011, 2012, 2013, and 2014, respectively [P = .001 for trend]) as the use of cefuroxime prophylactic injections increased (11.1%, 14.4%, 32.8%, 64.8%, and 79.1% in 2010, 2011, 2012, 2013, and 2014, respectively [P = .001 for trend]). After multivariate adjustment, the risk of POE was reduced with the use of cefuroxime (odds ratio, 0.61 [95% CI, 0.56-0.68]). The retinal safety of an injection of cefuroxime, which was assessed by multiadjusted odds of retinal cystoid macular edema, was not increased for patients receiving cefuroxime injections (odds ratio, 0.86 [95% CI, 0.71-1.05]). For patients with a perioperative capsular rupture of the lens (the major risk factor for POE), the incidence of POE was lower for those who received an injection of cefuroxime than for those who did not (0.37% vs 0.51%, respectively [P = .001]), whereas an increased risk of cystoid macular edema was not identified for those who received or did not receive an injection of cefuroxime (5.6% vs 7.3%, respectively [P = .12]).CONCLUSIONS AND RELEVANCE:These data suggest that, in routine practice, the intracameral injection of cefuroxime at the conclusion of cataract surgery is associated with a lower risk of POE and is safe for patients with or without a perioperative capsular rupture. While these data might be used to support the consideration of its routine use to prevent POE, in the absence of a randomized clinical trial, they cannot prove a direct cause-and-effect relationship between the injection of cefuroxime and POE

Magnetic Resonance Imaging of Parotid Gland Tumors

International audienceThe aim of the study was to evaluate dynamic contrast-enhanced magnetic resonance (MR) imaging in the characterization of parotid gland tumors

Classifying Idiopathic Rapid Eye Movement Sleep Behavior Disorder, Controls, and Mild Parkinson's Disease Using Gait Parameters

International audienceBackgroundSubtle gait changes associated with idiopathic rapid eye movement sleep behavior disorder (iRBD) could allow early detection of subjects with future synucleinopathies.ObjectiveThe aim of this study was to create a multiclass model, using statistical learning from probability distribution of gait parameters, to distinguish between patients with iRBD, healthy control subjects (HCs), and patients with Parkinson's disease (PD).MethodsGait parameters were collected in 21 participants with iRBD, 21 with PD, and 21 HCs, matched for age, sex, and education level. Lasso sparse linear regression explored gait features able to classify the three groups.ResultsThe final model classified iRBD from HCs and from patients with PD equally well, with 95% accuracy, 100% sensitivity, and 90% specificity.ConclusionsGait parameters and a pretrained statistical model can robustly distinguish participants with iRBD from HCs and patients with PD. This could be used to screen subjects with future synucleinopathies in the general population and to identify a conversion threshold to PD

French medical-administrative database for epidemiology and safety in ophthalmology (EPISAFE): The EPISAFE collaboration program in cataract surgery

Mini review.Medical-administrative databases are an important source of big data to assess the epidemiology of diseases and interventions, compare drugs, and investigate rare adverse events. We describe the French national health insurance system databases and the Epidemiology and Safety (EPISAFE) collaboration program in ophthalmology and illustrate the paper with recent studies that used the databases to investigate cataract surgery. The SystSme national d'information inter-regime de l'assurance maladie (SNIIR-AM) is one of the largest databases of medical and administrative data for a general population, covering nearly 65 million people. The SNIIR-AM database links data for all outpatientreimbursed health expenditures, hospitalization in all 1,546 French private or public healthcare facilities, and date of death. The use of this database provides information at the scale of the entire country, allowing measurement of the impact of changes in practices and new guidelines. Between 2009 and 2012, a total of 2,717,203 eyes in 1,817,865 patients underwent cataract surgery in France, and the incidence of cataract surgery increased from 9.86 to 11.08/1,000 personyears. The 4-year cumulative risk of retinal detachment was 0.99%, and patients < 60 years of age were at higher risk of retinal detachment. The incidence of pseudophakic cystoid macular edema was 0.95%. From 2005 to 2014, from data including more than 6 million procedures, the incidence of endophthalmitis after cataract surgery decreased from 0.15 to 0.05%. The EPISAFE collaboration program encompasses the key issues facing ophthalmology, including public health and public policy concerning disease incidence and prevalence, safety and adverse event monitoring, and clinical guidelines

A Pharmacoepidemiological study of intravitreal drug consumption in the first 12 months of treatment. The EPIdemiology and SAFEty collaboration

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