Jimenezmilne7591

BACKGROUND The onset of freezing of gait (FOG) represents a turning point in the lives of patients with Parkinson's disease (PD). FOG increases fall risk and is associated with worse physical and mental health related quality of life, thus increasing disease burden. Moreover, therapeutic studies aiming to ameliorate freezing have had limited success. In a step towards pre-emptive therapy to delay or prevent the onset of FOG, this prospective cohort study set out to uncover clinical markers of conversion to FOG. OBJECTIVE Investigate clinical markers of conversion to FOG. METHODS Sixty PD patients without FOG were followed up for two years and underwent extensive clinical testing each year. FOG classification was made with the New Freezing of Gait Questionnaire. Clinical predictors of conversion to FOG were investigated using univariate analysis and through building a multivariable model using all measured components. RESULTS Twelve patients developed FOG during the study (Incidence 11.5% per year). Due to thending informs future studies aimed at FOG prevention.BACKGROUND Dramatic improvements in spinal muscular atrophy (SMA) treatment have changed the prognosis for patients with this disease, leading to important new questions. selleckchem Gathering representative, real-world data about the long-term efficacy and safety of emerging SMA interventions is essential to document their impact on patients and caregivers. OBJECTIVES This registry will assess outcomes in patients with genetically confirmed SMA and provide information on the effectiveness and long-term safety of approved and emerging treatments. DESIGN AND METHODS RESTORE is a prospective, multicenter, multinational observational registry. Patients will be managed according to usual clinical practice. Both newly recruitedSMAtreatment centers and sites involved in existing SMA registries, including iSMAC, Treat-NMD, French SMA Assistance Publique- Hôpitaux de Paris (AP-HP), Cure-SMA, SMArtCARE, will be eligible to participate; de novo; sites already participating in another registry may be included via consortium agreements. Data from patients enrolled in partnering registries will be shared with the RESTORE Registry and data for newly diagnosed patients will be added upon enrollment. Patients will be enrolled over a 5-year period and followed for 15 years or until death. Assessments will include SMA history and treatment, pulmonary, nutritional, and motor milestones, healthcare resource utilization, work productivity, activity impairment, adverse events, quality of life, caregiver burden, and survival.StatusRecruitment started in September 2018. As of January 3, 2020, 64 patients were enrolled at 25 participating sites. CONCLUSIONS The RESTORE Registry has begun recruiting recently diagnosed patients with genetically confirmed SMA, enabling assessment of both short- and long-term patient outcomes.BACKGROUND Extensive genetic screening results in the identification of thousands of rare variants that are difficult to interpret. Because of its sheer size, rare variants in the titin gene (TTN) are detected frequently in any individual. Unambiguous interpretation of molecular findings is almost impossible in many patients with myopathies or cardiomyopathies. OBJECTIVE To identify clinically irrelevant and relevant TTN variants and refine the current classification criteria to increase specificity for use in TTN-associated skeletal muscle disorders. METHODS We used the guidelines issued by the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) to re-analyze TTN genetic findings from our patient cohort. RESULTS We identified potential clinically relevant and irrelevant variants. At the same time, we also identified in the classification guidelines three rules that are not applicable to titin-related skeletal muscle disorders and thirteen rules that require disease-/gene-specific adjustments. CONCLUSIONS We suggest adjustments are made to the guidelines. We provide frequency thresholds to facilitate filtering of candidate causative variants and guidance for the use and interpretation of functional data and co-segregation evidence. We also strongly encourage a closer cross-field collaboration among all the different specialists working on titin.BACKGROUND Studies have found that individuals with mild cognitive impairment (MCI) exhibit a range of deficits outside the realm of primary explicit memory, yet the role of response speed and implicit learning in older adults with MCI have not been established. OBJECTIVE The current study aims to explore and document response speed and implicit learning in older adults with neuropsychologically defined MCI using a simple serial reaction (SRT) task. In addition, the study aims to explore the feasibility of a novel utilization of the simple cognitive task using machine learning procedures as a proof of concept. METHOD Participants were 22 cognitively healthy older adults and 20 older adults with MCI confirmed through comprehensive neuropsychological evaluation. Two-sample t-test, multivariate regression, and mixed-effect models were used to investigate group difference in response speed and implicit learning on the SRT task. We also explored the potential utility of SRT feature analysis through random forest classification. RESULTS With demographic variables controlled, the MCI group showed overall slower reaction time and higher error rate compared to the cognitively healthy volunteers. Both groups showed significant simple motor learning and implicit learning. The learning patterns were not statistically different between the two groups. Random forest classification achieved overall accuracy of 80.9%. CONCLUSIONS Individuals with MCI demonstrated slower reaction time and higher error rate compared to cognitively healthy volunteers but demonstrated largely preserved motor learning and implicit sequence learning. Preliminary results from random forest classification using features from SRT performance supported further research in this area.Light modulation plays an important role in understanding the pathology of brain disorders and improving brain function. Optogenetic techniques can activate or silence targeted neurons with high temporal and spatial accuracy and provide precise control, and have recently become a method for quick manipulation of genetically identified types of neurons. Photobiomodulation (PBM) is light therapy that utilizes non-ionizing light sources, including lasers, light emitting diodes, or broadband light. It provides a safe means of modulating brain activity without any irreversible damage and has established optimal treatment parameters in clinical practice. This manuscript reviews 1) how optogenetic approaches have been used to dissect neural circuits in animal models of Alzheimer's disease, Parkinson's disease, and depression, and 2) how low level transcranial lasers and LED stimulation in humans improves brain activity patterns in these diseases. State-of-the-art brain machine interfaces that can record neural activity and stimulate neurons with light have good prospects in the future.