Validating a method for the estimate of gait spatio-temporal parameters with IMUs data on healthy and impaired people from two clinical centers

Instrumented gait analysis offers objective clinical outcome assessment. To this purpose, inertial measurement units (IMUs) represent nowadays a very effective solution due to their limited cost, ease of use and improved wearability. The aim of this study was to apply a well-documented IMU-based method to measure gait spatio-temporal parameters in a large number of healthy and gait-impaired subjects, and evaluate its robustness and validity across two clinical centers. Overall, the results of this work represent a robust and reliable foundation for the clinical use of the proposed IMU based method for gait parameters estimation

Using a Body-Fixed Sensor to Identify Subclinical Gait Difficulties in Older Adults with IADL Disability: Maximizing the Output of the Timed Up and Go

Objective: The identification and documentation of subclinical gait impairments in older adults may facilitate the appropriate use of interventions for preventing or delaying mobility disability. We tested whether measures derived from a single body-fixed sensor worn during traditional Timed Up and Go (TUG) testing could identify subclinical gait impairments in community dwelling older adults without mobility disability. Methods: We used data from 432 older adults without dementia (mean age 83.30±7.04 yrs, 76.62% female) participating in the Rush Memory and Aging Project. The traditional TUG was conducted while subjects wore a body-fixed sensor. We derived measures of overall TUG performance and different subtasks including transitions (sit-to-stand, stand-to-sit), walking, and turning. Multivariate analysis was used to compare persons with and without mobility disability and to compare individuals with and without Instrumental Activities of Daily Living disability (IADL-disability), all of whom did not have mobility disability. Results: As expected, individuals with mobility disability performed worse on all TUG subtasks (p<0.03), compared to those who had no mobility disability. Individuals without mobility disability but with IADL disability had difficulties with turns, had lower yaw amplitude (p<0.004) during turns, were slower (p<0.001), and had less consistent gait (p<0.02). Conclusions: A single body-worn sensor can be employed in the community-setting to complement conventional gait testing. It provides a wide range of quantitative gait measures that appear to help to identify subclinical gait impairments in older adults

Projected health-care resource needs for an effective response to COVID-19 in 73 low-income and middle-income countries: a modelling study

BACKGROUND; : Since WHO declared the COVID-19 pandemic a Public Health Emergency of International Concern, more than 20 million cases have been reported, as of Aug 24, 2020. This study aimed to identify what the additional health-care costs of a strategic preparedness and response plan (SPRP) would be if current transmission levels are maintained in a status quo scenario, or under scenarios where transmission is increased or decreased by 50%.; METHODS; : The number of COVID-19 cases was projected for 73 low-income and middle-income countries for each of the three scenarios for both 4-week and 12-week timeframes, starting from June 26, 2020. An input-based approach was used to estimate the additional health-care costs associated with human resources, commodities, and capital inputs that would be accrued in implementing the SPRP. FINDINGS: The total cost estimate for the COVID-19 response in the status quo scenario was US$52.45 billion over 4 weeks, at$8.60 per capita. For the decreased or increased transmission scenarios, the totals were $33.08 billion and$61.92 billion, respectively. Costs would triple under the status quo and increased transmission scenarios at 12 weeks. The costs of the decreased transmission scenario over 12 weeks was equivalent to the cost of the status quo scenario at 4 weeks. By percentage of the overall cost, case management (54%), maintaining essential services (21%), rapid response and case investigation (14%), and infection prevention and control (9%) were the main cost drivers.; INTERPRETATION; : The sizeable costs of a COVID-19 response in the health sector will escalate, particularly if transmission increases. Instituting early and comprehensive measures to limit the further spread of the virus will conserve resources and sustain the response.; FUNDING; : WHO, and UK Foreign Commonwealth and Development Office

Human recombinant glutamate oxaloacetate transaminase 1 (GOT1) supplemented with oxaloacetate induces a protective effect after cerebral ischemia

Blood glutamate scavenging is a novel and attractive protecting strategy to reduce the excitotoxic effect of extracellular glutamate released during ischemic brain injury. Glutamate oxaloacetate transaminase 1 (GOT1) activation by means of oxaloacetate administration has been used to reduce the glutamate concentration in the blood. However, the protective effect of the administration of the recombinant GOT1 (rGOT1) enzyme has not been yet addressed in cerebral ischemia. The aim of this study was to analyze the protective effect of an effective dose of oxaloacetate and the human rGOT1 alone and in combination with a non-effective dose of oxaloacetate in an animal model of ischemic stroke. Sixty rats were subjected to a transient middle cerebral artery occlusion (MCAO). Infarct volumes were assessed by magnetic resonance imaging (MRI) before treatment administration, and 24 h and 7 days after MCAO. Brain glutamate levels were determined by in vivo MR spectroscopy (MRS) during artery occlusion (80 min) and reperfusion (180 min). GOT activity and serum glutamate concentration were analyzed during the occlusion and reperfusion period. Somatosensory test was performed at baseline and 7 days after MCAO. The three treatments tested induced a reduction in serum and brain glutamate levels, resulting in a reduction in infarct volume and sensorimotor deficit. Protective effect of rGOT1 supplemented with oxaloacetate at 7 days persists even when treatment was delayed until at least 2 h after onset of ischemia. In conclusion, our findings indicate that the combination of human rGOT1 with low doses of oxaloacetate seems to be a successful approach for stroke treatment.Ministeiro de Economía y Competitividad de EspañaXunta de Galicia /Consellería Economía IndustriaXunta de Galicia/ Consellería EducaciónInstituto de Salud Carlos IIISpanish Research Network on Cerebrovascular Diseases RETICS-INVICTUSFundación Mútua MadrileñaEuropean Union program FEDEREspaña. Ministerio de Economía y Competitividad/SAF2011-30517Xunta de Galicia /Consellería Economía Industria/10PXIB918282PRXunta de Galicia / Consellería Educación/ CN2011/010Instituto de Salud Carlos III/PI11/00909Instituto de Salud Carlos III/CP12/03121Spanish Research Network on Cerebrovascular Diseases RETICS-INVICTUS /RD12/0014Instituto de Salud Carlos III/PI10/00449Instituto de Salud Carlos III/PI12/0311

Associations between Quantitative Mobility Measures Derived from Components of Conventional Mobility Testing and Parkinsonian Gait in Older Adults

Objective: To provide objective measures which characterize mobility in older adults assessed in the community setting and to examine the extent to which these measures are associated with parkinsonian gait. Methods: During conventional mobility testing in the community-setting, 351 ambulatory non-demented Memory and Aging Project participants wore a belt with a whole body sensor that recorded both acceleration and angular velocity in 3 directions. We used measures derived from these recordings to quantify 5 subtasks including a) walking, b) transition from sit to stand, c) transition from stand to sit, d) turning and e) standing posture. Parkinsonian gait and other mild parkinsonian signs were assessed with a modified version of the original Unified Parkinson’s Disease Rating Scale (mUPDRS). Results: In a series of separate regression models which adjusted for age and sex, all 5 mobility subtask measures were associated with parkinsonian gait and accounted for 2% to 32% of its variance. When all 5 subtask measures were considered in a single model, backward elimination showed that measures of walking sit to stand and turning showed independent associations with parkinsonian gait and together accounted for more than 35% of its variance. Cross-validation using data from a 2nd group of 258 older adults showed similar results. In similar analyses, only walking was associated with bradykinesia and sway with tremor. Interpretation Quantitative mobility subtask measures vary in their associations with parkinsonian gait scores and other parkinsonian signs in older adults. Quantifying the different facets of mobility has the potential to facilitate the clinical characterization and understanding the biologic basis for impaired mobility in older adults

Genetic markers of Restless Legs Syndrome in Parkinson disease

INTRODUCTION: Several studies proposed that Restless Legs Syndrome (RLS) and Parkinson disease (PD) may be clinically and/or etiologically related. To examine this hypothesis, we aimed to determine whether the known RLS genetic markers may be associated with PD risk, as well as with PD subtype. METHODS: Two case-control cohorts from Tel-Aviv and New-York, including 1133 PD patients and 867 controls were genotyped for four RLS-related SNPs in the genes MEIS1, BTBD9, PTPRD and MAP2K5/SKOR1. The association between genotype, PD risk and phenotype was tested using multivariate regression models. RESULTS: None of the tested SNPs was significantly associated with PD risk, neither in any individual cohort nor in the combined analysis after correction for multiple comparisons. The MAP2K5/SKOR1 marker rs12593813 was associated with higher frequency of tremor in the Tel-Aviv cohort (61.0% vs. 46.5%, p = 0.001, dominant model). However, the risk allele for tremor in this gene has been associated with reduced RLS risk. Moreover, this association did not replicate in Tremor-dominant PD patients from New-York. CONCLUSION: RLS genetic risk markers are not associated with increased PD risk or subtype in the current study. Together with previous genetic, neuropathological and epidemiologic studies, our results further strengthen the notion that RLS and PD are likely to be distinct entities

Virtual Reality as a Tool for Evaluation of Repetitive Rhythmic Movements in the Elderly and Parkinson's Disease Patients

This work presents an immersive Virtual Reality (VR) system to evaluate, and potentially treat, the alterations in rhythmic hand movements seen in Parkinson's disease (PD) and the elderly (EC), by comparison with healthy young controls (YC). The system integrates the subjects into a VR environment by means of a Head Mounted Display, such that subjects perceive themselves in a virtual world consisting of a table within a room. In this experiment, subjects are presented in 1st person perspective, so that the avatar reproduces finger tapping movements performed by the subjects. The task, known as the finger tapping test (FT), was performed by all three subject groups, PD, EC and YC. FT was carried out by each subject on two different days (sessions), one week apart. In each FT session all subjects performed FT in the real world (FTREAL) and in the VR (FTVR); each mode was repeated three times in randomized order. During FT both the tapping frequency and the coefficient of variation of inter-tap interval were registered. FTVR was a valid test to detect differences in rhythm formation between the three groups. Intra-class correlation coefficients (ICC) and mean difference between days for FTVR (for each group) showed reliable results. Finally, the analysis of ICC and mean difference between FTVR vs FTREAL, for each variable and group, also showed high reliability. This shows that FT evaluation in VR environments is valid as real world alternative, as VR evaluation did not distort movement execution and detects alteration in rhythm formation. These results support the use of VR as a promising tool to study alterations and the control of movement in different subject groups in unusual environments, such as during fMRI or other imaging studies

GBA mutations are associated with Rapid eye movement sleep behavior disorder

Rapid eye movement sleep behavior disorder and GBA mutations are both associated with Parkinson’s disease. The GBA gene was sequenced in idiopathic rapid eye movement sleep behavior disorder patients (n = 265), and compared to controls (n = 2240). Rapid eye movement sleep behavior disorder questionnaire was performed in an independent Parkinson’s disease cohort (n = 120). GBA mutations carriers had an OR of 6.24 (10.2% in patients vs. 1.8% in controls, P < 0.0001) for rapid eye movement sleep behavior disorder, and among Parkinson’s disease patients, the OR for mutation carriers to have probable rapid eye movement sleep behavior disorder was 3.13 (P = 0.039). These results demonstrate that rapid eye movement sleep behavior disorder is associated with GBA mutations, and that combining genetic and prodromal data may assist in identifying individuals susceptible to Parkinson’s disease

Cancer outcomes among Parkinson's disease patients with leucine rich repeat kinase 2 mutations, idiopathic Parkinson's disease patients, and nonaffected controls

BACKGROUND: Increased cancer risk has been reported in Parkinson's disease (PD) patients carrying the leucine rich repeat kinase 2 (LRRK2) G2019S mutation (LRRK2-PD) in comparison with idiopathic PD (IPD). It is unclear whether the elevated risk would be maintained when compared with unaffected controls. METHODS: Cancer outcomes were compared among 257 LRRK2-PD patients, 712 IPD patients, and 218 controls recruited from 7 LRRK2 consortium centers using mixed-effects logistic regression. Data were then pooled with a previous study to examine cancer risk between 401 LRRK2-PD and 1946 IPD patients. RESULTS: Although cancer prevalence was similar among LRRK2-PD patients (32.3%), IPD patients (27.5%), and controls (27.5%; P = 0.33), LRRK2-PD had increased risks of leukemia (odds ratio [OR] = 4.55; 95% confidence interval [CI], 1.46-10.61) and skin cancer (OR = 1.61; 95% CI, 1.09-2.37). In the pooled analysis, LRRK2-PD patients had also elevated risks of leukemia (OR = 9.84; 95% CI, 2.15-44.94) and colon cancer (OR = 2.34; 95% CI, 1.15-4.74) when compared with IPD patients. CONCLUSIONS: The increased risks of leukemia as well as skin and colon cancers among LRRK2-PD patients suggest that LRRK2 mutations heighten risks of certain cancers. © 2019 International Parkinson and Movement Disorder Society