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Hepatitis C virus (HCV) infection poses a significant public health challenge and often leads to long-term health complications and even death. Parkinson's disease (PD) is a progressive neurodegenerative disorder with a proposed viral etiology. HCV infection and PD have been previously suggested to be related. This work aimed to identify potential biomarkers and pathways that may play a role in the joint development of PD and HCV infection. Using BioOptimatics-bioinformatics driven by mathematical global optimization-, 22 publicly available microarray and RNAseq datasets for both diseases were analyzed, focusing on sex-specific differences. Our results revealed that 19 genes, including MT1H, MYOM2, and RPL18, exhibited significant changes in expression in both diseases. Pathway and network analyses stratified by sex indicated that these gene expression changes were enriched in processes related to immune response regulation in females and immune cell activation in males. These findings suggest a potential link between HCV infection and PD, highlighting the importance of further investigation into the underlying mechanisms and potential therapeutic targets involved.

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Extracellular vesicles (EVs) are produced, secreted, and targeted by most human cells, including cells that compose nervous system tissues. EVs carry several types of biomolecules, such as lipids, proteins and microRNA, and can function as signaling agents in physiological and pathological processes. In this chapter, we will focus on EVs and their cargo secreted by brain cells, especially neurons and glia, and how these aspects are affected in pathological conditions. The chapter covers neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis, as well as several psychiatric disorders, namely schizophrenia, autism spectrum disorder and major depressive disorder. This chapter also addresses other types of neurological dysfunctions, epilepsy and traumatic brain injury. EVs can cross the blood brain barrier, and thus brain EVs may be detected in more accessible peripheral tissue, such as circulating blood. Alterations in EV composition and contents can therefore impart valuable clues into the molecular etiology of these disorders, and serve biomarkers regarding disease prevalence, progression and treatment. EVs can also be used to carry drugs and biomolecules into brain tissue, considered as a promising drug delivery agent for neurological diseases. Therefore, although this area of research is still in its early development, it offers great potential in further elucidating and in treating neurological disorders.

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Objective: This study evaluates machine learning algorithms' effectiveness in classifying Parkinson's disease and Huntington's disease based on biomarker data obtained non-invasively from patients and healthy controls. Methods: Datasets containing biomarker data (x, y, and z values of accelerometers) from sensors were collected from Parkinson's disease, Huntington's disease patients, and healthy controls. An automatic selection model method was implemented for disease classification, using a unique Mexican database of human gait biomarkers, which we consider the only one of its kind. Random forest, random subspace method, and K-star algorithms were employed, with parameters optimized through an automated model selection. Results: The study achieved a 0.893 precision rate for Parkinson's disease and Huntington's disease using the random subspace method. The findings underscore the potential of machine learning techniques in medical diagnosis, particularly in neurological disorders. Conclusion: The automatic selection model method demonstrated efficacy in classifying Parkinson's disease and Huntington's disease based on non-invasive biomarker data. This research contributes to advancing non-invasive diagnostic approaches in neurological disorders, highlighting the significance of machine learning in healthcare.

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This work comprehends the development and characterization of a carbon black-based electrode modified with Au microflowers to increase its effect as a capacitance biosensor for the determination of PARK7/DJ-1. Due to its high surface-to-volume ratio and biocompatibility, Au particles are suitable for antibody binding, and by monitoring surface capacitance, it is possible to identify the immune-pair interaction. Au microflowers allowed the adequate immobilization of Parkinsonian-related proteins: PARK7/DJ-1 and its antibody. The protein is associated with several antioxidant mechanisms, but its abnormal concentrations or mutations can be the cause of the loss of dopaminergic neurons, leading to Parkinson's disease. The device was characterized by scanning electron microscopy and cyclic voltammetry, revealing the flower-like structures and the electrochemically-interest enhancements they provide, such as increased heterogeneous electron transfer rate coefficient and electroactive area. The self-assembled monolayers of different molecules were optimized with the aid of 22 central composite experiments and a linear calibration curve was obtained between 0.700 and 120 ng mL-1 of PARK7/DJ-1, with a limit of detection of 0.207 ng mL-1. The data confirms that the addition of Au microflowers enhanced the electrochemical signal of the device, as well as allowed for the determination of an early stage Parkinson's disease biomarker with appreciable analytical performance.

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REM Sleep Behavioral Disorder (RBD) is a parasomnia marked by the maintenance of muscle tone during REM sleep. Evidence has placed RBD as one of the possible prodromal stages of Parkinson's Disease (PD), but data on the proportion of people with PD who have had symptoms of RBD are limited. This study aimed to investigate the history of symptoms compatible with RBD in a population with PD. The sample was composed by 73 patients with clinically diagnosed PD being followed up at a reference outpatient setting, compared to 73 age- and sex-matched individuals with no PD. The evaluation of symptoms compatible with RBD was performed using the Brazilian version of the RBD Screening Questionnaire (RBDSQ). The prevalence of symptoms compatible with RBD was 65 % for PD and 10.09 % for controls. The RBDSQ score was significantly higher in the PD group (6.03 ± 0.35) in comparison to the control group (2.38 ± 0.23). The odds ratio for presenting previous RBD-compatible symptoms was 12.09 in favor of positive PD cases. PD diagnosis has the following diagnostic properties in relation to presenting RBD symptoms: sensitivity of 0.65, specificity of 0.86, positive predictive value of 0.82 and negative predictive value of 0.71. In conclusion, the proportion of PD patients showing RBD symptoms is high, corroborating the expected neuroprogression of the disease on a case-control design comprising outpatient PD cases. Clinical practitioners should include evaluations of RBD-compatible symptoms during the PD assessment and, if positive, forward to a sleep specialist.

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BACKGROUND: Evidence has suggested that cognitive decline may be a risk factor for freezing of gait (FOG) in Parkinson's disease (PD). Complex and challenging exercises have been suggested as potential rehabilitation strategies to decrease FOG severity and improve cognition; however, it is unknown whether improvement in cognition would explain decreased FOG severity following exercise. OBJECTIVE: In this secondary analysis, we evaluated the effects of the adapted resistance training with instability (ARTI-complex and challenging exercises) compared with traditional motor rehabilitation (TMR-without challenging exercises) on cognitive function in people with FOG of PD. We also verified whether cognitive improvement explains the decrease in FOG previously published. METHODS: Participants were randomized to either the experimental group (ARTI, n = 17) or the active control group (TMR, n = 15). Both training groups exercised 3 times a week for 12 weeks (80-90 minute each session). FOG severity (FOG ratio from inertial sensors during a 360° turning-in-place task), frontal lobe function (Frontal Assessment Battery [FAB]), global cognition (Montreal Cognitive Assessment [MoCA]), and attention and psychomotor speed (Digit Symbol Substitution Test [DSST]) were evaluated before and after interventions. RESULTS: Only the ARTI group improved FAB, MoCA, and DSST scores at posttraining. In addition, ARTI was more effective than TMR in improving FAB scores at posttraining. The changes in FAB scores explained the changes in FOG ratio following ARTI (R2 = .43, P < .01). CONCLUSIONS: This pilot study suggests that ARTI, a complex and challenging training, improves cognition in people with FOG of PD. Improvements in frontal lobe function with ARTI help explain decreased FOG severity.

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BACKGROUND: Scientific research based on model organisms can help to understand the biology of Parkinson's Disease, the second most prevalent neurodegenerative disease. Drosophila melanogaster mutant for the gene parkin, homologous to human's PARK2, exhibit well-characterized phenotypes including loss of dopaminergic neurons, lower survival and motor defects. Through the transcriptomic analysis of an exceptional case of reversible neurodegeneration in Drosophila, our group identified that the gene pretaporter, homologous to TXNDC5 of humans, was downregulated in the reversal phase. Here, we explore the hypothesis that the lack of expression of pretaporter will restrain phenotypes observed in Drosophila parkin mutants. METHODS: After establishing by immunochemistry that Pretaporter is expressed in PPL1 dopaminergic neurons, we constructed pretaporter-parkin double mutants flies to investigate the hypothesis through immunohistochemistry, survival and climbing assays. CONCLUSIONS: It was found that the loss-of-function mutation in pretaporter significatively restrains the phenotype caused by the loss-of-function mutation in parkin in several key aspects: it abolished the loss of PPL1 neurons normally seen in parkin mutant flies, promoted their survival in both sexes and reduced the decay in motor ability in parkin female flies. We propose that the absence of Pretaporter in parkin mutant flies prevents the death of dopaminergic neurons by rendering them resistant to Draper-mediated-phagocytosis.

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Recently, a single-neuron degeneration model has been proposed to understand the development of idiopathic Parkinson's disease based on (i) the extremely slow development of the degenerative process before the onset of motor symptoms and during the progression of the disease and (ii) the fact that it is triggered by an endogenous neurotoxin that does not have an expansive character, limiting its neurotoxic effect to single neuromelanin-containing dopaminergic neurons. It has been proposed that aminochrome is the endogenous neurotoxin that triggers the neurodegenerative process in idiopathic Parkinson's disease by triggering mitochondrial dysfunction, oxidative stress, neuroinflammation, dysfunction of both lysosomal and proteasomal protein degradation, endoplasmic reticulum stress and formation of neurotoxic alpha-synuclein oligomers. Aminochrome is an endogenous neurotoxin that is rapidly reduced by flavoenzymes and/or forms adducts with proteins, which implies that it is impossible for it to have a propagative neurotoxic effect on neighboring neurons. Interestingly, the enzymes DT-diaphorase and glutathione transferase M2-2 prevent the neurotoxic effects of aminochrome. Natural compounds present in fruits, vegetables and other plant products have been shown to activate the KEAP1/Nrf2 signaling pathway by increasing the expression of antioxidant enzymes including DT-diaphorase and glutathione transferase. This review analyzes the possibility of searching for natural compounds that increase the expression of DT-diaphorase and glutathione transferase through activation of the KEAP1/Nrf2 signaling pathway.

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Among the myriad of neurodegenerative diseases, mitochondrial dysfunction represents a nexus regarding their pathogenic processes, in which Parkinson's disease (PD) is notable for inherent vulnerability of the dopaminergic pathway to energy deficits and oxidative stress. Underlying this dysfunction, the occurrence of defects in complex I (CI) derived from molecular alterations in its subunits has been described in the literature. However, the mechanistic understanding of the processes mediating the occurrence of mitochondrial dysfunction mediated by CI deficiency in PD remains uncertain and subject to some inconsistencies. Therefore, this review analyzed existing evidence that may explain the relationship between molecular alterations in the core subunits of CI, recognized for their direct contribution to its enzymatic performance, and the pathogenesis of PD. As a result, we discussed 47 genetic variants in the 14 core subunits of CI, which, despite some discordant results, were predominantly associated with varying degrees of deficiency in complex enzymatic activity, as well as defects in supercomplex biogenesis and CI itself. Finally, we hypothesized about the relationship of the described alterations with the pathogenesis of PD and offered some suggestions that may aid in the design of future studies aimed at elucidating the relationship between such alterations and PD.

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AIM: To investigate the hypothesis supporting the link between periodontitis and dopaminergic neuron degeneration. MATERIALS AND METHODS: Adult male Wistar rats were used to induce dopaminergic neuronal injury with 6-hydroxydopamine (6-OHDA) neurotoxin and experimental periodontitis via ligature placement. Motor function assessments were conducted before and after periodontitis induction in controls and 6-OHDA-injury-induced rats. Tissue samples from the striatum, jaw and blood were collected for molecular analyses, encompassing immunohistochemistry of tyrosine hydroxylase, microglia and astrocyte, as well as micro-computed tomography, to assess alveolar bone loss and for the analysis of striatal oxidative stress and plasma inflammatory markers. RESULTS: The results indicated motor impairment in 6-OHDA-injury-induced rats exacerbated by periodontitis, worsening dopaminergic striatal degeneration. Periodontitis alone or in combination with 6-OHDA-induced lesion was able to increase striatal microglia, while astrocytes were increased by the combination only. Periodontitis increased striatal reactive oxygen species levels and plasma tumour necrosis factor-alpha levels in rats with 6-OHDA-induced lesions and decreased the anti-inflammatory interleukin-10. CONCLUSIONS: This study provides original insights into the association between periodontitis and a neurodegenerative condition. The increased inflammatory pathway associated with both 6-OHDA-induced dopaminergic neuron lesion and periodontal inflammatory processes corroborates that the periodontitis-induced systemic inflammation may aggravate neuroinflammation in Parkinson's-like disease, potentially hastening disease progression.

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Although the most prominent symptoms of Parkinson's disease (PD) are those impacting movement, cognitive dysfunction is prevalent and often presents early in the disease process. Individuals with cognitive symptoms of PD often complete cognitive screening, making it important to identify factors associated with cognitive screening performance to ensure prompt and accurate detection of cognitive impairments. Objective: Despite a body of research examining relationships between motor symptoms and cognitive dysfunction in PD, no prior study has undertaken a systematic review of the magnitude of the relationship between motor symptoms and cognitive screening performance in PD. Methods: This study was a systematic review and meta-analysis of the relationship between cognitive screening performance, as assessed by the Montreal Cognitive Assessment (MoCA), and motor symptoms of PD. After the systematic screening, 20 studies were included, and meta-regressions using mixed-effects models were conducted. Results: Motor symptoms across included studies were relatively mild, but average MoCA scores were at the established cutoff for risk of dementia in PD. The average disease duration was 5 years. Consistent with hypotheses, more severe motor symptoms were associated with lower MoCA scores (r=-0.22 (95%CI -0.29 to -0.16), p<0.001), indicating worse cognitive functioning. Conclusion: The results indicate a significant negative correlation between MoCA performance and motor symptoms of PD. Average MoCA scores captured early disease-stage cognitive impairment when motor symptoms remained relatively mild. Serial screening for cognitive impairment beginning early in the disease course may be of benefit to ensure that cognitive dysfunction is detected as it arises.

Embora os sintomas mais proeminentes da doença de Parkinson (DP) sejam aqueles que afetam o movimento, a disfunção cognitiva é prevalente e muitas vezes se apresenta no início do processo da doença. Indivíduos com sintomas cognitivos de DP frequentemente realizam triagem cognitiva, tornando importante identificar os fatores associados ao desempenho da triagem cognitiva para garantir a detecção rápida e precisa de deficiências cognitivas. Objetivo: Apesar de um conjunto de pesquisas examinar as relações entre sintomas motores e disfunção cognitiva na DP, nenhum trabalho anterior realizou uma revisão sistemática da magnitude da relação entre sintomas motores e desempenho na triagem cognitiva na DP. Métodos: O presente estudo foi uma revisão sistemática e meta-análise da relação entre o desempenho da triagem cognitiva, avaliada pela Avaliação Cognitiva de Montreal (Montreal Cognitive Assessment ­ MoCA), e os sintomas motores da DP. Após triagem sistemática, 20 estudos foram incluídos e foram realizadas meta-regressões utilizando modelos de efeitos mistos. Resultados: Os sintomas motores nos estudos incluídos foram relativamente leves, mas as pontuações médias do MoCA estavam no ponto de corte estabelecido para o risco de demência na DP. A duração média da doença foi de 5 anos. Consistente com as hipóteses, sintomas motores mais graves foram associados a pontuações mais baixas no MoCA, r=-0,22 (IC95% -0,29 to -0,16), p<0,001), indicando pior funcionamento cognitivo. Conclusão: Os resultados indicam uma correlação negativa significativa entre o desempenho no MoCA e os sintomas motores da DP. As pontuações médias do MoCA capturaram o comprometimento cognitivo em estágio inicial da doença, quando os sintomas motores permaneceram relativamente leves. O rastreio em série do comprometimento cognitivo que começa no início do curso da doença pode ser benéfico para garantir que a disfunção cognitiva seja detectada à medida que surge.

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SUMOylation is a post-translational modification essential for various biological processes. SUMO proteins bind to target substrates in a three-step enzymatic pathway, which is rapidly reversible by the action of specific proteases, known as SENPs. Studies have shown that SUMOylation is dysregulated in several human disorders, including neurodegenerative diseases that are characterized by the progressive loss of neurons, mitochondrial dysfunction, deficits in autophagy, and oxidative stress. Considering the potential neuroprotective roles of SUMOylation, the aim of this study was to investigate the effects of SENP3 knockdown in H4 neuroglioma cells exposed to rotenone, an in vitro model of cytotoxicity that mimics dopaminergic loss in Parkinson's disease (PD). The current data show that SENP3 knockdown increases SUMO-2/3 conjugates, which is accompanied by reduced levels of the mitochondrial fission protein Drp1 and increased levels of the mitochondrial fusion protein OPA1. Of high interest, SENP3 knockdown prevented rotenone-induced superoxide production and cellular death. Taken together, these findings highlight the importance of SUMOylation in maintaining mitochondrial homeostasis and the neuroprotective potential of this modification in PD.

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INTRODUCTION: Parkinson's disease (PD) is a progressive neurological condition resulting from the degeneration of dopaminergic neurons in the substantia nigra. Impaired manual dexterity and cognitive impairment are common symptoms and are often associated with recurrent adverse events in this population. OBJECTIVE: To verify the association between cognitive performance and manual dexterity in people with PD. METHODS: This is a cross-sectional observational study, with 29 participants, who underwent cognitive and manual dexterity assessments, and the following tools were used: Trail Making Test, box and block test (BBT), Learning Test of Rey and Nine Hole Peg Test. Descriptive statistics for clinical and demographic data were performed using mean and standard deviation, and data normality was assessed using the Shapiro-Wilk test. Spearman's nonparametric test was used to determine the correlation between variables. RESULTS: Our findings revealed significant associations between cognitive performance and manual dexterity. The nine-hole peg test positively correlated with TMT-Part A and Part B, establishing a relationship between manual dexterity and cognitive functions such as attention and mental flexibility. On the other hand, BBT showed an inverse relationship with TMT-Part B, indicating that longer time on this task was associated with lower manual dexterity. CONCLUSION: Fine manual dexterity had a significant correlation with visual search skills and motor speed, while gross motor dexterity had a negative correlation with cognitive skills. No significant results were demonstrated regarding the interaction between manual dexterity and memory.

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OBJECTIVE: To evaluate the orofacial myofunctional characteristics, masticatory performance and facial thermal profile in individuals with Parkinson disease (PD) and spinocerebellar ataxia (SCA3), comparing with healthy control ones. METHOD: Seventy-two participants aged between 30 and 85 years were evaluated and divided into PD, SCA3 and control groups. The assessments included clinical evaluation using the Orofacial Myofunctional Evaluation with Scores protocol (orofacial structures, mastication, swallowing and breathing aspects), masticatory performance assessed with a colour-changeable chewing gum and infrared thermography. The Kruskal-Wallis, one-way ANOVA and Wilcoxon tests were applied. RESULTS: With the exception of face and tongue, a difference was seen in the cheek, maxillomandibular relationship, lips, mentalis muscle and palate appearance and posture between patients and healthy control participants. Orofacial mobility, swallowing and masticatory function also scored higher in the control group. The SCA3 and PD groups required more time to eat the test-food and showed greater facial temperature asymmetries than the control one (p < 0.05). Masticatory performance measured by chewing gum did not differ. CONCLUSION: Facial temperature asymmetries, swallowing and masticatory function scores and the time needed by the SCA3 and PD groups to eat the test-food were different from healthy participants, drawing attention to the impaired orofacial functions in patients with neurodegenerative disorders.

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Resumen El incremento de la incidencia y prevalencia de las patologías Parkinson y Alzheimer generan una alarma en los sistemas de salud debido a sus consecuencias en los individuos, familia y sociedad. El desarrollo de tratamientos no farmacológicos dirigidos a la rehabilitación cognitiva abre nuevas posibilidades para el incremento de la calidad de vida de estos pacientes.

Abstract The increase in the incidence and prevalence of Parkinson's and Alzheimer's diseases is causing alarm in health systems due to their consequences on individuals, families, and society. The development of non-pharmacological treatments aimed at cognitive rehabilitation opens new possibilities for increasing the quality of life of these patients.

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Background: The Parkinson's Disease-Cognitive Rating Scale (PD-CRS) is a widely used tool for detecting mild cognitive impairment (MCI) in Parkinson's Disease (PD) patients, however, the neuroanatomical underpinnings of this test's outcomes require clarification. This study aims to: (a) investigate cortical volume (CVol) and cortical thickness (CTh) disparities between PD patients exhibiting mild cognitive impairment (PD-MCI) and those with preserved cognitive abilities (PD-IC); and (b) identify the structural correlates in magnetic resonance imaging (MRI) of overall PD-CRS performance, including its subtest scores, within a non-demented PD cohort. Materials and methods: This study involved 51 PD patients with Hoehn & Yahr stages I-II, categorized into two groups: PD-IC (n = 36) and PD-MCI (n = 15). Cognitive screening evaluations utilized the PD-CRS and the Montreal Cognitive Assessment (MoCA). PD-MCI classification adhered to the Movement Disorder Society Task Force criteria, incorporating extensive neuropsychological assessments. The interrelation between brain morphology and cognitive performance was determined using FreeSurfer. Results: Vertex-wise analysis of the entire brain demonstrated a notable reduction in CVol within a 2,934 mm2 cluster, encompassing parietal and temporal regions, in the PD-MCI group relative to the PD-IC group. Lower PD-CRS total scores correlated with decreased CVol in the middle frontal, superior temporal, inferior parietal, and cingulate cortices. The PD-CRS subtests for Sustained Attention and Clock Drawing were associated with cortical thinning in distinct regions: the Clock Drawing subtest correlated with changes in the parietal lobe, insula, and superior temporal cortex morphology; while the PD-CRS frontal-subcortical scores presented positive correlations with CTh in the transverse temporal, medial orbitofrontal, superior temporal, precuneus, fusiform, and supramarginal regions. Additionally, PD-CRS subtests for Semantic and Alternating verbal fluency were linked to CTh changes in orbitofrontal, temporal, fusiform, insula, and precentral regions. Conclusion: PD-CRS performance mirrors neuroanatomical changes across extensive fronto-temporo-parietal areas, covering both lateral and medial cortical surfaces, in PD patients without dementia. The observed changes in CVol and CTh associated with this cognitive screening tool suggest their potential as surrogate markers for cognitive decline in PD. These findings warrant further exploration and validation in multicenter studies involving independent patient cohorts.

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Parkinson's disease (PD) is the second most common neurodegenerative disease globally. Current drugs only alleviate symptoms without halting disease progression, making rodent models essential for researching new therapies and understanding the disease better. However, selecting the right model is challenging due to the numerous models and protocols available. Key factors in model selection include construct, face, and predictive validity. Construct validity ensures the model replicates pathological changes seen in human PD, focusing on dopaminergic neurodegeneration and a-synuclein aggregation. Face validity ensures the model's symptoms mirror those in humans, primarily reproducing motor and non-motor symptoms. Predictive validity assesses if treatment responses in animals will reflect those in humans, typically involving classical pharmacotherapies and surgical procedures. This review highlights the primary characteristics of PD and how these characteristics are validated experimentally according to the three criteria. Additionally, it serves as a valuable tool for researchers in selecting the most appropriate animal model based on established validation criteria.

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Parkinson's disease (PD) is a neurodegenerative disorder characterized by diverse symptoms, where accurate diagnosis remains challenging. Traditional clinical observation methods often result in misdiagnosis, highlighting the need for biomarker-based diagnostic approaches. This study utilizes ultraperformance liquid chromatography coupled to an electrospray ionization source and quadrupole time-of-flight untargeted metabolomics combined with biochemometrics to identify novel serum biomarkers for PD. Analyzing a Brazilian cohort of serum samples from 39 PD patients and 15 healthy controls, we identified 15 metabolites significantly associated with PD, with 11 reported as potential biomarkers for the first time. Key disrupted metabolic pathways include caffeine metabolism, arachidonic acid metabolism, and primary bile acid biosynthesis. Our machine learning model demonstrated high accuracy, with the Rotation Forest boosting model achieving 94.1% accuracy in distinguishing PD patients from controls. It is based on three new PD biomarkers (downregulated: 1-lyso-2-arachidonoyl-phosphatidate and hypoxanthine and upregulated: ferulic acid) and surpasses the general 80% diagnostic accuracy obtained from initial clinical evaluations conducted by specialists. Besides, this machine learning model based on a decision tree allowed for visual and easy interpretability of affected metabolites in PD patients. These findings could improve the detection and monitoring of PD, paving the way for more precise diagnostics and therapeutic interventions. Our research emphasizes the critical role of metabolomics and machine learning in advancing our understanding of the chemical profile of neurodegenerative diseases.

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INTRODUCTION: Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neurons' degeneration of the substantia nigra, presenting with motor and non-motor symptoms. We hypothesized that altered diffusion metrics are associated with clinical symptoms in de novo PD patients. METHODS: Fractional Anisotropy (FA) and Mean (MD), Axial (AD), and Radial Diffusivity (RD) were assessed in 55 de novo PD patients (58.62 ± 9.85 years, 37 men) and 55 age-matched healthy controls (59.92 ± 11.25 years, 34 men). Diffusion-weighted images and clinical variables were collected from the Parkinson's Progression Markers Initiative study. Tract-based spatial statistics were used to identify white matter (WM) changes, and fiber tracts were localized using the JHU-WM tractography atlas. Motor and non-motor symptoms were evaluated in patients. RESULTS: We observed higher FA values and lower RD values in patients than controls in various fiber tracts (p-TFCE < 0.05). No significant MD or AD difference was observed between groups. Diffusion metrics of several regions significantly correlated with non-motor (state and trait anxiety and daytime sleepiness) and axial motor symptoms in the de novo PD group. No correlations were observed between diffusion metrics and other clinical symptoms evaluated. CONCLUSION: Our findings suggest microstructural changes in de novo PD fiber tracts; however, limited associations with clinical symptoms reveal the complexity of PD pathology. They may contribute to understanding the neurobiological changes underlying PD and have implications for developing targeted interventions. However, further longitudinal research with larger cohorts and consideration of confounding factors are necessary to elucidate the underlying mechanisms of these diffusion alterations in de novo PD.

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Objective: After deep brain stimulation (DBS), patients with Parkinson's disease (PD) typically still present significant gait and postural stability problems, and thus additional interventions are needed. In this way, our purpose was evaluate the comparative effectiveness of treadmill training, with and without body weight support, on balance outcomes among patients with PD after DBS. Methods: Eleven patients with PD that were using bilateral subthalamic nucleus DBS were evaluated using Time Up and Go test (TUG); Berg Balance Scale (BBS) and Static Posturography. In phase 1, all subjects participated in 8-weeks of treadmill training in conjunction with conventional physiotherapy. After six weeks (wash-out), each patient then participated in a subsequent 8-weeks of treadmill training with partial body weight support. Results: After the phase 1, there were improvements on the cognitive TUG performance (Before: 15.7 ± 1,8 sec; After: 13.7 ± 3.1 sec; p < 0.01) and an increase of anteroposterior and medio-lateral body oscillation with eyes closed. After the phase 2, there were improvements in conventional (Before: 12.3 ± 2.0 sec; After: 10.7 ± 1.7 sec; p < 0.01) and cognitive (Before: 14.6 ± 3.5 sec; After: 12.5 ± 1.6 sec; p < 0.05) TUG performances. There were no significant changes in the Berg Balance Scale following either training protocol. Conclusion: Both trainings improved static and dynamic balance and had similar results; however, supported treadmill training seemed to be a potentially superior option, as patients tended to feel safer. Level of Evidence II, therapeutic studies - investigation of treatment outcomes.

Objetivo: Mesmo após a estimulação cerebral profunda (ECP), os pacientes com doença de Parkinson (DP) muitas vezes ainda apresentam problemas significativos de marcha e estabilidade postural, e, portanto, intervenções adicionais são necessárias. Avaliar a eficácia comparativa do treinamento em esteira, com e sem suporte de peso corporal, nos resultados de equilíbrio de pacientes com DP após ECP. Métodos: Onze pacientes com DP em uso de ECP bilateral do núcleo subtalâmico foram avaliados pelos testes Time Up and Go (TUG), escala de equilíbrio de Berg (EEB) e posturografia estática. Na fase 1, todos participaram de oito semanas de treinamento em esteira em conjunto com fisioterapia convencional. Após seis semanas (wash-out), cada paciente participou de oito semanas subsequentes de treinamento em esteira com suporte parcial de peso corporal. Resultados: Depois da fase 1, houve melhora no desempenho cognitivo do TUG (antes: 15,7 ± 1,8 s; depois: 13,7 ± 3,1 s; p < 0,01) e aumento da oscilação anteroposterior e médio-lateral do corpo com os olhos fechados. Após a fase 2, os resultados do TUG convencional (antes: 12,3 ± 2,0 seg; depois: 10,7 ± 1,7 seg; p < 0,01) e cognitivo (antes: 14,6 ± 3,5 s; depois: 12,5 ± 1,6 s; p < 0,05) demonstraram melhora. Os protocolos de treinamento não causaram mudanças significativas na EEB.. Conclusão: Ambos os treinos melhoraram o equilíbrio estático e dinâmico e tiveram resultados semelhantes; no entanto, o treinamento em esteira com suporte é uma opção potencialmente superior, uma vez que os pacientes tendiam a se sentir mais seguros. Nível de Evidência II, estudos terapêuticos - investigação de resultados de tratamento.