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BackgroundTo date, no medication has slowed the progression of Parkinson's disease (PD). Preclinical, epidemiological, and experimental data on humans all support many benefits of endurance exercise among persons with PD. The key question is whether there is a definitive additional benefit of exercising at high intensity, in terms of slowing disease progression, beyond the well-documented benefit of endurance training on a treadmill for fitness, gait, and functional mobility. This study will determine the efficacy of high-intensity endurance exercise as first-line therapy for persons diagnosed with PD within 3 years, and untreated with symptomatic therapy at baseline.MethodsThis is a multicenter, randomized, evaluator-blinded study of endurance exercise training. The exercise intervention will be delivered by treadmill at 2 doses over 18 months: moderate intensity (4 days/week for 30 min per session at 60-65% maximum heart rate) and high intensity (4 days/week for 30 min per session at 80-85% maximum heart rate). We will randomize 370 participants and follow them at multiple time points for 24 months. The primary outcome is the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor score (Part III) with the primary analysis assessing the change in MDS-UPDRS motor score (Part III) over 12 months, or until initiation of symptomatic antiparkinsonian treatment if before 12 months. Secondary outcomes are striatal dopamine transporter binding, 6-min walk distance, number of daily steps, cognitive function, physical fitness, quality of life, time to initiate dopaminergic medication, circulating levels of C-reactive protein (CRP), and brain-derived neurotrophic factor (BDNF). Tertiary outcomes are walking stride length and turning velocity.DiscussionSPARX3 is a Phase 3 clinical trial designed to determine the efficacy of high-intensity, endurance treadmill exercise to slow the progression of PD as measured by the MDS-UPDRS motor score. Establishing whether high-intensity endurance treadmill exercise can slow the progression of PD would mark a significant breakthrough in treating PD. It would have a meaningful impact on the quality of life of people with PD, their caregivers and public health.Trial registrationClinicalTrials.gov NCT04284436 . Registered on February 25, 2020.

Background. Gait impairments are common in Parkinson's disease (PD) and increase falls risk. Visual cues can improve gait in PD, particularly freezing of gait (FOG), but mechanisms involved in visual cue response are unknown. This study aimed to examine brain activity in response to visual cues in people with PD who do (PD+FOG) and do not report FOG (PD-FOG) and explore relationships between attention, brain activity and gait. Methods. Mobile EEG measured brain activity during gait in 20 healthy older adults and 43 PD participants (n=22 PD+FOG, n=21 PD-FOG). Participants walked for 2-minutes with and without visual cues (transverse lines to step over). We report power spectral density (PSD) in Delta (1-4 Hz), Theta (4-7 Hz), Alpha (8-12 Hz), Beta (14-24 Hz) and Gamma (30-50 Hz) bands within clusters of similarly brain localized independent component sources. Results. PSDs within the parietal and occipital lobes were altered when walking with visual cues in PD, particularly in PD+FOG. Between group, differences suggested that parietal sources in PD, particularly with PD+FOG, had larger activity compared to healthy older adults when walking. Within group, visual cues altered brain activity in PD, particularly in PD+FOG, within visual processing brain regions. In PD participants, brain activity differences with cues correlated with gait improvements, and in PD+FOG those with worse attention required more visual attentional processing (reduced alpha PSD) in the occipital lobe. Conclusions. Visual cues improve gait and influence brain activity during walking in PD, particularly in PD+FOG. Findings may allow development of more effective therapeutics.

Clinical neurophysiology studies can contribute important information about the physiology of human movement and the pathophysiology and diagnosis of different movement disorders. Some techniques can be accomplished in a routine clinical neurophysiology laboratory and others require some special equipment. This review, initiating a series of articles on this topic, focuses on the methods and techniques. The methods reviewed include EMG, EEG, MEG, evoked potentials, coherence, accelerometry, posturography (balance), gait, and sleep studies. Functional MRI (fMRI) is also reviewed as a physiological method that can be used independently or together with other methods. A few applications to patients with movement disorders are discussed as examples, but the detailed applications will be the subject of other articles.

Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS; the most common phenotype of corticobasal degeneration) are tauopathies with a relentless course, usually starting in the mid-60s and leading to death after an average of 7 years. There is as yet no specific or disease-modifying treatment. Clinical deficits in PSP are numerous, involve the entire neuraxis, and present as several discrete phenotypes. They center on rigidity, bradykinesia, postural instability, gait freezing, supranuclear ocular motor impairment, dysarthria, dysphagia, incontinence, sleep disorders, frontal cognitive dysfunction, and a variety of behavioral changes. CBS presents with prominent and usually asymmetric dystonia, apraxia, myoclonus, pyramidal signs, and cortical sensory loss. The symptoms and deficits of PSP and CBS are amenable to a variety of treatment strategies but most physicians, including many neurologists, are reluctant to care for patients with these conditions because of unfamiliarity with their multiplicity of interacting symptoms and deficits. CurePSP, the organization devoted to support, research, and education for PSP and CBS, created its CurePSP Centers of Care network in North America in 2017 to improve patient access to clinical expertise and develop collaborations. The directors of the 25 centers have created this consensus document outlining best practices in the management of PSP and CBS. They formed a writing committee for each of 12 sub-topics. A 4-member Steering Committee collated and edited the contributions. The result was returned to the entire cohort of authors for further comments, which were considered for incorporation by the Steering Committee. The authors hope that this publication will serve as a convenient guide for all clinicians caring for patients with PSP and CBS and that it will improve care for patients with these devastating but manageable disorders.

In a scenario characterised by mitigation concerns and calls for greater resilience in the energy sector, energy audits (EAs) emerge as an essential mean for enhancing end-use energy consumption awareness and efficiency. Such a tool allows us to assess the different energy carriers consumed in a productive sector, offering insight into existing energy efficiency improvement opportunities. This opens avenues for research to devise an econometrics-based methodology that encapsulate production sites and their environmental essentials. This paper contributes to the literature by exploiting the EAs received by the Italian National agency for New technologies, Energy, and Sustainable Economic Development (ENEA) in 2019 from the Italian plastics manufacturing sector, matched with Italian firm-based data extracted from the Analisi Informatizzata delle Aziende Italiane (Italian company information and business intelligence) (AIDA) database. In particular, we investigate how the implementation of energy efficiency measures (EEMs) is influenced by a set of contextual factors, as well as features relating to the companies and EEMs themselves. The empirical investigation focuses on the EAs submitted to ENEA in 2019, which was strategically chosen due to its unique data availability and adequacy for extensive analysis. The selection of 2019 is justified as it constitutes the second mandatory reporting period for energy audits, in contrast to the 2022 data, which are currently undergoing detailed refinement. In line with the literature, the adopted empirical approach involves the use of both the OLS and logistic regression models. Empirical results confirm the relevance of economic and financial factors in guiding the decisions surrounding the sector's energy performance, alongside the analogous influence of the technical characteristics of the measures themselves and of the firms' strategies. In particular, the OLS model with no fixed effects shows that a one-percent variation in investments is associated with an increase in savings performance equal to 0.63%. As for the OLS model, including fixed effects, the elasticity among the two variables concerned reaches 0.87%, while in the logistic regression, if the investment carried out by the production sites increases, the expected percentage change in the probability that the energy-saving performance is above its average is about 187.77%. Contextual factors that prove to be equally influential include the incentive mechanism considered and the traits of the geographical area in which the companies are located. Relevant policy implications derived from this analysis include the importance of reducing informational barriers about EEMs and increasing technical assistance, which can be crucial for identifying and implementing effective energy solutions. [ABSTRACT FROM AUTHOR]