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Journal of Nanobiotechnology Jun 2024Parkinson's disease (PD) is the second largest group of neurodegenerative diseases, and its existing drug treatments are not satisfactory. Natural cell membrane drugs...
Parkinson's disease (PD) is the second largest group of neurodegenerative diseases, and its existing drug treatments are not satisfactory. Natural cell membrane drugs are used for homologous targeting to enhance efficacy. In this study, microfluidic electroporation chip prepared mesenchymal stem cell-derived neuron-like cell membrane-coated curcumin PLGA nanoparticles (MM-Cur-NPs) was synthesized and explored therapeutic effect and mechanism in PD. MM-Cur-NPs can protect neuron from damage, restore mitochondrial membrane potential and reduce oxidative stress in vitro. In PD mice, it also can improve movement disorders and restore damaged TH neurons. MM-Cur-NPs was found to be distributed in the brain and metabolized with a delay within 24 h. After 1 h administration, MM-Cur-NPs were distributed in brain with a variety of neurotransmitters were significantly upregulated, such as dopamine. Differentially expressed genes of RNA-seq were enriched in the inflammation regulation, and it was found the up-expression of anti-inflammatory factors and inhibited pro-inflammatory factors in PD. Mechanically, MM-Cur-NPs can not only reduce neuronal apoptosis, inhibit the microglial marker IBA-1 and inflammation, but also upregulate expression of neuronal mitochondrial protein VDAC1 and restore mitochondrial membrane potential. This study proposes a therapeutic strategy provide neuroprotective effects through MM-Cur-NPs therapy for PD.
Topics: Animals; Mesenchymal Stem Cells; Mice; Apoptosis; Nanoparticles; Neurons; Parkinson Disease; Inflammation; Cell Membrane; Membrane Potential, Mitochondrial; Curcumin; Mice, Inbred C57BL; Microfluidics; Male; Oxidative Stress
PubMed: 38918856
DOI: 10.1186/s12951-024-02587-1 -
BMC Psychiatry Jun 2024Children and adolescents, after natural and man-made disasters, often exhibit various psychological, emotional, and behavioral issues, showing a range of clinical... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Children and adolescents, after natural and man-made disasters, often exhibit various psychological, emotional, and behavioral issues, showing a range of clinical symptoms related to post-traumatic stress disorder (PTSD) and depression. This review used a network meta-analysis (NMA) approach to compare and rank psychological interventions for PTSD and depression in children and adolescents after exposure to natural and man-made disasters.
METHODS
Randomized studies of psychosocial interventions for PTSD and depression in children and adolescents exposed to natural and man-made disasters were identified. PTSD and depression symptoms at postintervention and 1-12 month follow-up are the outcomes. The standardized mean differences (SMDs) between pairs of interventions at postintervention and follow-up were pooled. Mean effect sizes with 95% credible intervals (CI) were calculated, and the ranking probabilities for all interventions were estimated using the surface under the cumulative ranking curve. Study quality was assessed with version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2).
RESULTS
In total, 26 studies with 4331 participants were included in this NMA. Eye movement desensitization and reprocessing therapy (EMDR) (SMD = - 0.67; 95% CI - 1.17 to - 0.17), exposure therapy (ET) (SMD = - 0.66; 95% CI - 1.11 to - 0.22), and cognitive behavioral therapy (CBT) (SMD = - 0.62; 95% CI - 0.90 to - 0.34) were significantly more effective for PTSD at postintervention than inactive intervention. EMDR (SMD = - 0.72; 95% CI - 1.11 to - 0.33) and ET (SMD = - 0.62; 95% CI - 0.97 to - 0.27) were associated with a higher reduction in PTSD symptoms at follow-up than inactive intervention. EMDR (SMD = - 0.40; 95% CI - 0.78 to - 0.03) and play therapy (PT) (SMD = - 0.37; 95% CI - 0.62 to - 0.12) were significantly more effective for depression at postintervention than inactive intervention. For all psychological interventions in reducing depression symptoms at follow-up compared with inactive intervention, the differences were not significant.
CONCLUSION
EMDR appears to be most effective in reducing PTSD and depression in children and adolescents exposed to natural and man-made disasters. In addition, ET and CBT are potentially effective in reducing PTSD symptoms at postintervention, while PT is beneficial in managing depression symptoms at the treatment endpoint.
Topics: Humans; Stress Disorders, Post-Traumatic; Adolescent; Child; Network Meta-Analysis; Psychosocial Intervention; Disasters; Eye Movement Desensitization Reprocessing; Depression; Natural Disasters; Randomized Controlled Trials as Topic; Cognitive Behavioral Therapy
PubMed: 38918741
DOI: 10.1186/s12888-024-05924-8 -
BMC Neurology Jun 2024People with Parkinson's disease (PD) are very sensitive to the effects of stress. The prevalence of stress-related neuropsychiatric symptoms is high, and acute stress...
Study protocol for the MIND-PD study: a randomized controlled trial to investigate clinical and biological effects of mindfulness-based cognitive therapy in people with Parkinson's disease.
BACKGROUND
People with Parkinson's disease (PD) are very sensitive to the effects of stress. The prevalence of stress-related neuropsychiatric symptoms is high, and acute stress worsens motor symptoms. Animal studies suggest that chronic stress may accelerate disease progression, but evidence for this in humans is lacking. Mindfulness-based interventions (MBIs) train participants to focus on the present moment, on purpose and without judgement. Previous studies suggest that MBIs may alleviate stress and reduce depression and anxiety in PD. We aim to demonstrate the efficacy of Mindfulness-Based Cognitive Therapy (MBCT) as a non-pharmacologic treatment strategy for neuropsychiatric (and motor) symptoms in PD, and to identify the mechanisms underlying stress and stress reduction in PD.
METHODS
In a prospective randomized controlled trial (RCT), we investigate whether 8 weeks of MBCT, as compared to care as usual, can reduce symptoms of anxiety and depression in people with PD. We aim to include 124 PD patients, who experience mild-moderate symptoms of anxiety and depression, are eligible for magnetic resonance imaging (MRI) and naïve to mindfulness, and who have a disease duration ≤ 10 years. Every participant is followed for 12 months. Clinical and biochemical assessments take place at baseline (T0), after 2 months (T1), and after 12 months (T2); MRI assessments take place at T0 and T2. Our primary outcome is the total score on the Hospital Anxiety and Depression Scale (HADS) at T1, while correcting for the HADS score at T0, age, and gender. Beyond testing the effects of MBCT on symptoms of anxiety and depression in PD, we explore whether MBCT: (1) has an effect on motor symptom severity, (2) influences cerebral and biochemical markers of stress, and (3) leads to a change in biomarkers of PD progression.
DISCUSSION
MIND-PD is one of the first RCTs with a 1-year follow-up to investigate the effects of MBCT on symptoms of anxiety and depression in PD, and to explore possible mechanisms underlying stress and stress reduction in PD. Insight into these mechanisms can pave the way to new treatment methods in the future.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT05779137. Registered on 12 January 2023.
Topics: Aged; Female; Humans; Male; Middle Aged; Anxiety; Cognitive Behavioral Therapy; Depression; Magnetic Resonance Imaging; Mindfulness; Parkinson Disease; Prospective Studies; Randomized Controlled Trials as Topic; Stress, Psychological; Treatment Outcome
PubMed: 38918695
DOI: 10.1186/s12883-024-03736-7 -
BMC Genomics Jun 2024Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder featured by abnormal movements, arising from the extensive neuronal loss and glial...
Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder featured by abnormal movements, arising from the extensive neuronal loss and glial dysfunction in the striatum. Although the causes and pathogenetic mechanisms of HD are well established, the development of disease-modifying pharmacological therapies for HD remains a formidable challenge. Laduviglusib has demonstrated neuroprotective effects through the enhancement of mitochondrial function in the striatum of HD animal models. Ferroptosis is a nonapoptotic form of cell death that occurs as a consequence of lethal iron-dependent lipid peroxidation and mitochondrial dysfunction. However, the ferroptosis-related mechanisms underlying the neuroprotective effects of laduviglusib in the striatum of HD patients remain largely uncharted. In this study, we leveraged single-nucleus RNA sequencing data obtained from the striatum of HD patients in stages 2-4 to identify differentially expressed genes within distinct cell-type. We subsequently integrated these differentially expressed genes of HD, laduviglusib target genes and ferroptosis-related genes to predict the ferroptosis-related mechanisms underpinning the neuroprotective effects of laduviglusib in HD patients. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses unveiled that the effects of laduviglusib on direct pathway striatal projection neurons (dSPNs) is mainly associated with Th17 cell differentiation pathways. Conversely, its impact on indirect pathway striatal projection neurons (iSPNs) extends to the Neurotrophin signaling pathway, FoxO signaling pathway, and reactive oxygen species pathway. In microglia, laduviglusib appears to contribute to HD pathology via mechanisms related to Th17 cell differentiation and the FoxO signaling pathway. Further, molecular docking results indicated favorable binding of laduviglusib with PARP1 (associated with dSPNs and iSPNs), SCD (associated with astrocytes), ALOX5 (associated with microglia), and HIF1A (associated with dSPNs, iSPNs, and microglia). In addition, the KEGG results suggest that laduviglusib may enhance mitochondrial function and protect against neuronal loss by targeting ferroptosis-related signaling pathways, particularly mediated by ALOX5 in microglia. These findings provide valuable insights into the potential mechanisms through which laduviglusib exerts its effects on distinct cell-types within the HD striatum.
Topics: Ferroptosis; Huntington Disease; Humans; Corpus Striatum; Neuroprotective Agents
PubMed: 38918688
DOI: 10.1186/s12864-024-10534-5 -
Scientific Reports Jun 2024The objective of this study was to investigate the association between a Parkinson's disease (PD)-specific polygenic score (PGS) and protective lifestyle factors on age...
The objective of this study was to investigate the association between a Parkinson's disease (PD)-specific polygenic score (PGS) and protective lifestyle factors on age at onset (AAO) in PD. We included data from 4367 patients with idiopathic PD, 159 patients with GBA1-PD, and 3090 healthy controls of European ancestry from AMP-PD, PPMI, and Fox Insight cohorts. The association between PGS and lifestyle factors on AAO was assessed with linear and Cox proportional hazards models. The PGS showed a negative association with AAO (β = - 1.07, p = 6 × 10) in patients with idiopathic PD. The use of one, two, or three of the protective lifestyle factors showed a reduction in the hazard ratio by 21% (p = 0.0001), 44% (p < 2 × 10), and 55% (p < 2 × 10), compared to no use. An additive effect of aspirin (β = 7.62, p = 9 × 10) and PGS (β = - 1.58, p = 0.0149) was found for AAO without an interaction (p = 0.9993) in the linear regressions, and similar effects were seen for tobacco. In contrast, no association between aspirin intake and AAO was found in GBA1-PD (p > 0.05). In our cohort, coffee, tobacco, aspirin, and PGS are independent predictors of PD AAO. Additionally, lifestyle factors seem to have a greater influence on AAO than common genetic risk variants with aspirin presenting the largest effect.
Topics: Humans; Parkinson Disease; Female; Male; Middle Aged; Aged; Life Style; Age of Onset; Multifactorial Inheritance; Genetic Predisposition to Disease; Proportional Hazards Models; Glucosylceramidase; Case-Control Studies; Risk Factors; Aspirin
PubMed: 38918550
DOI: 10.1038/s41598-024-65640-x -
Scientific Reports Jun 2024Due to its involvement in physiological and pathological processes, histone deacetylase 6 (HDAC6) is considered a promising pharmaceutical target for several...
Due to its involvement in physiological and pathological processes, histone deacetylase 6 (HDAC6) is considered a promising pharmaceutical target for several neurological manifestations. However, the exact regulatory role of HDAC6 in the central nervous system (CNS) is still not fully understood. Hence, using a semi-automated literature screening technique, we systematically collected HDAC6-protein interactions that are experimentally validated and reported in the CNS. The resulting HDAC6 network encompassed 115 HDAC6-protein interactions divided over five subnetworks: (de)acetylation, phosphorylation, protein complexes, regulatory, and aggresome-autophagy subnetworks. In addition, 132 indirect interactions identified through HDAC6 inhibition were collected and categorized. Finally, to display the application of our HDAC6 network, we mapped transcriptomics data of Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis on the network and highlighted that in the case of Alzheimer's disease, alterations predominantly affect the HDAC6 phosphorylation subnetwork, whereas differential expression within the deacetylation subnetwork is observed across all three neurological disorders. In conclusion, the HDAC6 network created in the present study is a novel and valuable resource for the understanding of the HDAC6 regulatory mechanisms, thereby providing a framework for the integration and interpretation of omics data from neurological disorders and pharmacodynamic assessments.
Topics: Histone Deacetylase 6; Humans; Protein Interaction Maps; Nervous System Diseases; Alzheimer Disease; Phosphorylation; Acetylation; Parkinson Disease
PubMed: 38918466
DOI: 10.1038/s41598-024-65094-1 -
NPJ Parkinson's Disease Jun 2024Quantification of motor symptom progression in Parkinson's disease (PD) patients is crucial for assessing disease progression and for optimizing therapeutic...
Quantification of motor symptom progression in Parkinson's disease (PD) patients is crucial for assessing disease progression and for optimizing therapeutic interventions, such as dopaminergic medications and deep brain stimulation. Cumulative and heuristic clinical experience has identified various clinical signs associated with PD severity, but these are neither objectively quantifiable nor robustly validated. Video-based objective symptom quantification enabled by machine learning (ML) introduces a potential solution. However, video-based diagnostic tools often have implementation challenges due to expensive and inaccessible technology, and typical "black-box" ML implementations are not tailored to be clinically interpretable. Here, we address these needs by releasing a comprehensive kinematic dataset and developing an interpretable video-based framework that predicts high versus low PD motor symptom severity according to MDS-UPDRS Part III metrics. This data driven approach validated and robustly quantified canonical movement features and identified new clinical insights, not previously appreciated as related to clinical severity, including pinkie finger movements and lower limb and axial features of gait. Our framework is enabled by retrospective, single-view, seconds-long videos recorded on consumer-grade devices such as smartphones, tablets, and digital cameras, thereby eliminating the requirement for specialized equipment. Following interpretable ML principles, our framework enforces robustness and interpretability by integrating (1) automatic, data-driven kinematic metric evaluation guided by pre-defined digital features of movement, (2) combination of bi-domain (body and hand) kinematic features, and (3) sparsity-inducing and stability-driven ML analysis with simple-to-interpret models. These elements ensure that the proposed framework quantifies clinically meaningful motor features useful for both ML predictions and clinical analysis.
PubMed: 38918385
DOI: 10.1038/s41531-024-00742-x -
Neurology(R) Neuroimmunology &... Sep 2024Encephalitis with anti-N-methyl-d-aspartate receptor antibodies (anti-NMDARe) is a rare disorder characterized by cognitive impairment, psychosis, seizures, and abnormal...
OBJECTIVES
Encephalitis with anti-N-methyl-d-aspartate receptor antibodies (anti-NMDARe) is a rare disorder characterized by cognitive impairment, psychosis, seizures, and abnormal movements. Abnormal behaviors during REM sleep have not been described in anti-NMDARe.
METHODS
Patients were monitored by video-polysomnography on a first night followed by multiple sleep latency tests and 18 hours of bed rest.
RESULTS
Two patients with anti-NMDARe developed during the acute and postacute phase parasomnias including REM sleep behavior disorder and continuous finalistic quiet gesturing during a mixed N2/R sleep. The parasomnia disorder was improved by gabapentin and clonazepam.
DISCUSSION
Video-polysomnography avoids misdiagnosing these parasomnia behaviors for seizure or movement disorders and allows adequate treatment.
Topics: Humans; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Female; Adult; Male; Polysomnography; REM Sleep Parasomnias; REM Sleep Behavior Disorder; Parasomnias; Sleep, Slow-Wave; Clonazepam
PubMed: 38917379
DOI: 10.1212/NXI.0000000000200203 -
Neurologia I Neurochirurgia Polska Jun 2024We aimed to compare knowledge, opinions, and clinical experiences among Czech, Slovak, and Italian neurologists to identify potential educational gaps and unify...
AIM OF STUDY
We aimed to compare knowledge, opinions, and clinical experiences among Czech, Slovak, and Italian neurologists to identify potential educational gaps and unify understanding.
CLINICAL RATIONALE FOR STUDY
Functional neurological disorder (FND) is a disabling condition characterised by motor, sensory, or cognitive symptoms which are incompatible with other neurological disorders. Novel diagnostic and treatment approaches have improved FND management. However, the extent of their adoption, and any differences or similarities across European communities, remain to be established.
MATERIAL AND METHODS
Members of the Czech and Slovak Neurological Societies were invited via e-mail to participate in a 14- -item web-based survey investigating their approach to FND. This data was compared to results from a previous study involving 492 Italian neurologists.
RESULTS
232 questionnaires were completed by Czech and Slovak neurologists (CZ-SK). Similarities were found between CZ- -SK and Italian neurologists in their preference for the term 'FND' over other psychological-related terms and in explaining symptoms as due to abnormal functioning of the nervous system rather than attributing them to mental illness. However, only fewer than 5% in both groups thought that simulation was highly unlikely. Both groups reported relying on positive signs (e.g. inconsistency, distractibility) according to the current diagnostic criteria, but also a tendency to perform additional tests to exclude other causes. However, some differences were observed: Italian neurologists placed a greater emphasis on psychological factors including litigation. CZ-SK neurologists were more likely to suggest physiotherapy as a treatment option and to provide educational intervention for patients and their relatives.
CONCLUSIONS
Overall, our findings suggest that although Czech, Slovak, and Italian neurologists have adopted some new developments in the field of FND, significant gaps still exist in their understanding and common practices regarding conceptualisation, diagnosis, and treatment.
CLINICAL IMPLICATIONS
Our results suggest that promoting knowledge through postgraduate curricula and teaching courses for neurologists is necessary to optimise patient management in various European countries.
PubMed: 38916493
DOI: 10.5603/pjnns.99264 -
Cureus May 2024Background Thyroidectomy is a routinely performed surgical procedure used to treat benign, malignant, and some hormonal disorders of the thyroid that are not responsive...
Background Thyroidectomy is a routinely performed surgical procedure used to treat benign, malignant, and some hormonal disorders of the thyroid that are not responsive to medical therapy. Voice alterations following thyroid surgery are well-documented and often attributed to recurrent laryngeal nerve dysfunction. However, subtle changes in voice quality can persist despite anatomically intact laryngeal nerves. This study aimed to quantify post-thyroidectomy voice changes in patients with intact laryngeal nerves, focusing on fundamental frequency, first formant frequency, shimmer intensity, and maximum phonation duration. Methodology This cross-sectional study was conducted at a tertiary referral center in central India and focused on post-thyroidectomy patients with normal vocal cord function. Preoperative assessments included laryngeal endoscopy and voice recording using a computer program, with evaluations repeated at one and three months post-surgery. Patients with normal laryngeal endoscopic findings underwent voice analysis and provided feedback on subjective voice changes. The PRAAT version 6.2 software was utilized for voice analysis. Results The study included 41 patients with normal laryngoscopic findings after thyroid surgery, with the majority being female (85.4%) and the average age being 42.4 years. Hemithyroidectomy was performed in 41.4% of patients and total thyroidectomy in 58.6%, with eight patients undergoing central compartment neck dissection. Except for one patient, the majority reported no subjective change in voice following surgery. Objective voice analysis showed statistically significant changes in the one-month postoperative period compared to preoperative values, including a 5.87% decrease in fundamental frequency, a 1.37% decrease in shimmer intensity, and a 6.24% decrease in first formant frequency, along with a 4.35% decrease in maximum phonatory duration. These trends persisted at the three-month postoperative period, although values approached close to preoperative levels. Results revealed statistically significant alterations in voice parameters, particularly fundamental frequency and first formant frequency, with greater values observed in total thyroidectomy patients. Shimmer intensity also exhibited slight changes. Comparison between hemithyroidectomy and total thyroidectomy groups revealed no significant differences in fundamental frequency, first formant frequency, and shimmer. However, maximum phonation duration showed a significantly greater change in the hemithyroidectomy group at both one-month and three-month postoperative intervals. Conclusions This study on post-thyroidectomy patients with normal vocal cord movement revealed significant changes in voice parameters postoperatively, with most patients reporting no subjective voice changes. The findings highlight the importance of objective voice analysis in assessing post-thyroidectomy voice outcomes.
PubMed: 38916010
DOI: 10.7759/cureus.60873